Field of the Invention The present invention relates to methods of treating cardiovascular, inflammatory and other diseases, and specifically relates to combinations of compounds, compositions, and methods for their use in medicine, particularly in the prophylaxis and treatment of hyperlipidemic or inflammatory conditions such as are associated with atherosclerosis, hypercholesterolemia, coronary plaque inflammation and other cardiovascular diseases in mammals. More particularly, the invention relates to apical sodium co-dependent bile acid transport inhibitors, cyclooxygenase inhibitors (e. g., cyclooxygenase-2 selective inhibitors), and HMG-CoA reductase inhibitors.

Description of Related Art It is well-settled in the literature that hyperlipidemic conditions associated with elevated concentrations of total cholesterol and low-density lipoprotein (LDL) cholesterol are major risk factors for coronary heart disease and particularly atherosclerosis.

More recently, the role of inflammation in cardiovascular diseases has become much better understood. These findings serve to point out the acute need for

prophylactic and therapeutic strategies for cardiovascular disease that are effective in simultaneously controlling both inflammatory and hyperlipidemic conditions.

The non-steroidal anti-inflammatory drugs (NSAIDs) are known to prevent the formation of prostaglandins by inhibiting enzymes in the human arachidonic acid/prostaglandin pathway, in particular the enzyme cyclooxygenase (COX). For this reason the NSAIDs are effective in reducing the prostaglandin-induced pain and swelling associated with inflammatory processes. The recent discovery that there are two isoforms of the COX enzyme, COX-1 and COX-2, has given rise to new approaches for NSAID discovery and utilization, because it has been shown that COX-2 is the isoform specifically induced in many inflamed tissues. Many compounds have been identified which have activity as COX-2 inhibitors. A recent review of COX-2 selective inhibitors is provided by Carty and Marfat (Current Opinion in Anti-inflammatory & Immunomodulatory Investigational Drugs, 1 (20), 89-96 (1999)).

Atherosclerosis underlies most manifestations of coronary artery disease (CAD), a major cause of morbidity and mortality in modern society. High LDL cholesterol (above about 180 mg/dl) and low HDL cholesterol (below 35 mg/dl) have been shown to be important contributors to the development of atherosclerosis. Other diseases or risk factors, such as peripheral vascular disease, stroke, and hypercholesterolemia are also negatively affected by adverse HDL/LDL ratios.

A metabolic equilibrium generally exists between hepatic cholesterol and the bile acid pool. Interruption of the enterohepatic recirculation of bile acids results in a decrease in the liver bile acid pool and stimulates increased hepatic synthesis of bile acids from

cholesterol, eventually depleting the liver's pool of esterified cholesterol. In order to maintain the liver cholesterol levels necessary to support bile acid synthesis, de novo synthesis of cholesterol increases in hepatocytes via an up-regulation of the activity of 3- hydroxy-3-methylglutaryl coenzyme-A reductase (HMG-CoA reductase), while liver uptake of serum cholesterol is increased as a result of the up-regulation of the number of hepatic cell surface receptors for low density lipoprotein cholesterol. The latter increase in hepatic receptors directly leads to a reduction in serum LDL cholesterol levels. Abundant epidemiological data have accumulated which indicate that such reduction leads to significant mitigation of the disease symptoms of atherosclerosis. The discovery of specific ASBT inhibitors is further reviewed by Booker and Arbeeny (Cardiovasc. Pulmon. Renal Invest. Drugs, 2,208- 215 (2000)).

Various benzothiepine inhibitors of bile acid absorption have been disclosed by G. D. Searle (PCT Pat.

Appl. WO 93/321146) for numerous uses, including regulation of fatty acid metabolism and treatment of coronary vascular disease.

PCT patent application No. WO 92/18462 lists other benzothiepines for use as hypolipemic and hypocholesterolemic agents. Each of the benzothiepine hypolipemic and hypocholesterolemic agents described in these individual patent applications is limited by an amide bonded to the carbon adjacent the phenyl ring of the fused bicyclobenzothiepine ring.

PCT patent application no. WO 93/16055, which describes a number of hypolipidemic benzothiazepine compounds. Additional hypolipidemic benzothiazepine compounds (particularly 2,3,4,5-tetrahydrobenzo-1-thi-4-

azepine compounds) are disclosed in another PCT patent application no. WO 96/05188. Further hypolipidemic benzothiazepine compounds are also described in another world patent application (28).

Further ASBT inhibitor compounds include a class of lignan derivatives as described by Takashima et al.

(Atherosclerosis, 107,247-257 (1994)).

Another approach to the reduction of total cholesterol relies on the understanding that HMG-CoA reductase catalyzes the rate-limiting step in the biosynthesis of cholesterol (The Pharmacological Basis of Therapeutics, 9th ed., J. G. Hardman and L. E. Limberd, ed., McGraw-Hill, Inc., New York, pp. 884-888 (1996)). HMG- CoA reductase inhibitors (including the class of therapeutics commonly called"statins") reduce blood serum levels of LDL cholesterol by competitive inhibition of this biosynthetic step.

Numerous antihyperlipidemic agents having other modes of action also have been disclosed in the literature as being useful for the treatment of hyperlipidemic conditions and disorders. These agents include, for example, commercially available drugs such as nicotinic acid, bile acid sequestrants including cholestryramine and colestipol, probucol, and fibric acid derivatives including gemfibrozil and clofibrate.

Some combination therapies for the treatment of cardiovascular disease have been described in the literature. A combinations of an ASBT inhibitor with HMG- a CoA reductase inhibitor useful for the treatment of cardiovascular disease is disclosed in PCT patent application no. WO 98/40375.

PCT Patent Application No. WO 99/20110 describes a therapeutic combination of a COX-2 selective inhibitor with an HMG Co-A reductase inhibitor.

While the above references indicate the value of the known combination therapies in reducing the impact of hyperlipidemia on cardiovascular disease, there is a continuing urgent need to find safe, effective agents for the prophylaxis or treatment of cardiovascular and metabolic diseases involving both inflammatory and hyperlipidemic conditions. The novel combinations of the present invention exhibit improved efficacy, improved potency, and/or reduced dosing requirements for the active compounds relative to combination regimens previously disclosed in the published literature.

SUMMARY OF THE INVENTION To address the continuing need to find safe and effective agents for the prophylaxis and treatment of cardiovascular and other diseases, combination therapies of anti-inflammatory and anti-hyperlipidemic drugs are now disclosed.

Among its several embodiments, the present invention provides a combination therapy comprising treating a subject with an amount of an apical sodium co-dependent bile acid transport inhibitor and an amount of a cyclooxygenase-2 (COX-2) selective inhibitor or its prodrug, wherein the amount of the apical sodium co- dependent bile acid transport (ASBT) inhibitor and the amount of the cyclooxygenase-2 (COX-2) selective inhibitor together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the compounds. For example, one of the many embodiments of the present invention is a combination therapy comprising therapeutic dosages of an ASBT inhibitor selected from Table 2 and a cyclooxygenase-2 (COX-2) selective inhibitor selected from Tables 4,6 and

7A. A preferred embodiment of the present invention is a combination therapy comprising therapeutic dosages of a bicyclic benzothiepine ASBT inhibitor and a tricyclic cyclooxygenase-2 selective inhibitor.

In another embodiment, the present invention comprises a therapeutic combination containing an amount of an apical sodium co-dependent bile acid transport (ASBT) inhibitor and an amount of a cyclooxygenase-2 (COX- 2) selective inhibitor or its prodrug, and a pharmaceutically acceptable carrier, wherein the amount of the apical sodium co-dependent bile acid transport (ASBT) inhibitor and the amount of the cyclooxygenase-2 (COX-2) selective inhibitor together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the said compounds. For example, one of the many embodiments of the present invention is a combination comprising therapeutic dosages of an ASBT inhibitor selected from Table 2 and a cyclooxygenase-2 selective inhibitor selected from Tables 4,6 and 7A. A preferred embodiment of the present invention is a combination comprising therapeutic dosages of a benzothiepine ASBT inhibitor and a tricyclic cyclooxygenase-2 selective inhibitor.

Alternatively, an aspect of the present invention is a cardiovascular combination therapy comprising treating a subject with an amount of an apical sodium co-dependent bile acid transport inhibitor and an amount of a cyclooxygenase-2 (COX-2) selective inhibitor or its prodrug and an amount of an HMG-CoA reductase inhibitor, wherein the amount of the apical sodium co-dependent bile acid transport inhibitor, the amount of the cyclooxygenase-2 (COX-2) selective inhibitor and the amount of the HMG-CoA reductase inhibitor together constitute a hypercholesterolemia-related condition

effective amount or an inflammation-related condition effective amount of the said compounds. For example, one of the many embodiments of the present invention is a combination therapy comprising therapeutic dosages of an ASBT inhibitor selected from Table 2 and a cyclooxygenase- 2 selective inhibitor selected from Tables 4,6 and 7A and an HMG-CoA inhibitor selected from Table 8. A preferred embodiment of the present invention is a combination therapy comprising therapeutic dosages of a benzothiepine ASBT inhibitor, a tricyclic cyclooxygenase-2 (COX-2) selective inhibitor and a statin HMG-CoA inhibitor.

In yet another embodiment, the present invention comprises a therapeutic combination containing an amount of an apical sodium co-dependent bile acid transport inhibitor, an amount of a cyclooxygenase-2 (COX-2) selective inhibitor or its prodrug and an amount of an HMG-CoA reductase inhibitor, and a pharmaceutically acceptable carrier, wherein the amount of the apical sodium co-dependent bile acid transport inhibitor, the amount of the cyclooxygenase-2 (COX-2) selective inhibitor and the amount of the HMG-CoA inhibitor together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the said compounds. For example, one of the many embodiments of the present invention is a combination comprising therapeutic dosages of an ASBT inhibitor selected from Table 2 and a cyclooxygenase-2 (COX-2) selective inhibitor selected from Tables 4,6 and 7A and an HMG-CoA inhibitor selected from Table 8. A preferred embodiment of the present invention is a combination comprising therapeutic dosages of a benzothiepine ASBT inhibitor, a tricyclic cyclooxygenase-2 selective inhibitor and a statin HMG-CoA inhibitor.

In a further embodiment, the present invention provides a method for treating or preventing a hypercholesterolemia-related or an inflammation-related condition in a subject in need of such treatment or prevention, comprising treating the subject with an amount of an apical sodium co-dependent bile acid transport (ASBT) inhibitor and an amount of a chromene cyclooxygenase inhibitor (e. g., chromene cyclooxygenase-2 (COX-2) selective inhibitor) or its prodrug, wherein the amount of the apical sodium co-dependent bile acid transport inhibitor and the amount of the chromene cyclooxygenase inhibitor (e. g., chromene cyclooxygenase-2 (COX-2) selective inhibitor) together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the apical sodium co-dependent bile acid transport inhibitor and the chromene cyclooxygenase inhibitor (e. g., chromene cyclooxygenase-2 (COX-2) selective inhibitor).

In a further embodiment, the present invention provides a method for treating or preventing a hypercholesterolemia-related or an inflammation-related condition in a subject in need of such treatment or prevention, comprising treating the subject with an amount of an HMG Co-A reductase inhibitor and an amount of a chromene cyclooxygenase inhibitor (e. g., chromene cyclooxygenase-2 (COX-2) selective inhibitor) or its prodrug, wherein the amount of the HMG Co-A reductase inhibitor and the amount of the chromene cyclooxygenase inhibitor (e. g., chromene cyclooxygenase-2 (COX-2) selective inhibitor) together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the HMG Co-A reductase inhibitor and the chromene

cyclooxygenase inhibitor (e. g., chromene cyclooxygenase-2 (COX-2) selective inhibitor).

The present invention also provides a method for treating or preventing a hypercholesterolemia-related or an inflammation-related condition in a subject in need of such treatment or prevention, comprising treating the subject with an amount of an HMG Co-A reductase inhibitor and an amount of a source of valdecoxib, wherein the amount of the HMG Co-A reductase inhibitor and the amount of the source of valdecoxib together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the HMG Co-A reductase inhibitor and the source of valdecoxib.

Further scope of the applicability of the present invention will become apparent from the detailed description provided below. However, it should be understood that the following detailed description and examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent from this detailed description to those skilled in the art.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The following detailed description is provided to aid those skilled in the art in practicing the present invention. Even so, this detailed description should not be construed to unduly limit the present invention, inasmuch as modifications and variations in the embodiments discussed herein can be made by those of ordinary skill in the art without departing from the spirit or scope of the present inventive discovery.

The contents of each of the references cited herein, including the contents of the references cited within these primary references, are herein incorporated by reference in their entirety for all purposes. a. Definitions The following definitions are provided in order to aid the reader in understanding the detailed description of the present invention: The term"subject"as used herein refers to an animal, preferably a mammal, and particularly a human being, who has been the object of treatment, observation or experiment.

The terms"dosing"and"treatment"refer to any process, action, application, therapy, or the like, wherein a subject, and particularly a human being, is rendered medical aid with the object of improving the subject's condition, either directly or indirectly.

"Therapeutic compound"means a compound useful in the prophylaxis or treatment of a hyperlipidemic and/or inflammatory condition, including atherosclerosis, plaque inflammation and hypercholesterolemia.

"Combination therapy"means the administration of two or more therapeutic compounds to treat a hyperlipidemic and/or inflammatory condition, for example atherosclerosis, plaque inflammation, and hypercholesterolemia. Such administration encompasses co- administration of these therapeutic compounds in a substantially simultaneous manner, such as in a single capsule having a fixed ratio of active ingredients or in multiple, separate capsules for each compound. In addition, such administration also encompasses use of each type of therapeutic compound in a sequential manner. In either case, the treatment regimen will provide beneficial

effects of the drug combination in treating the cardiovascular or other condition.

The term"therapeutic combinationn refers to the administered therapeutic compounds themselves and to any pharmaceutically acceptable carriers used to provide dosage forms such that the beneficial effect of each therapeutic compound is realized by the subject at the desired time, whether the compounds are administered substantially simultaneously or sequentially.

The phrase"therapeutically effective"is intended to qualify the combined amount of therapeutic compounds in the combination therapy. This combined amount will achieve the goal of avoiding or reducing or eliminating the hyperlipidemic condition and/or inflammatory condition.

The terms"cyclooxygenase-2 selective inhibitor"and "COX-2 selective inhibitor/'interchangeably refer to a therapeutic compound which preferentially inhibits the COX-2 isoform of the enzyme cyclooxygenase.

The terms"cyclooxygenase-2 nonselective inhibitor" and"COX-2 nonselective inhibitor"interchangeably refer to a therapeutic compound which comparably inhibits both the COX-1 and COX-2 isoforms of the enzyme cyclooxygenase.

The term"prodrug"refers to a chemical compound that can be converted into a therapeutic compound by metabolic or simple chemical processes within the body of the subject. For example, a class of prodrugs of COX-2 inhibitors is described in US Patent No. 5,932,598, herein incorporated by reference. b. Combinations The combinations of the present invention will have a number of uses. For example, through dosage adjustment and medical monitoring, the individual dosages of the

therapeutic compounds used in the combinations of the present invention will be lower than are typical for dosages of the. therapeutic compounds when used in monotherapy. The dosage lowering will provide advantages including reduction of side effects of the individual therapeutic compounds when compared to monotherapy. In addition, fewer side effects of the combination therapy compared with monotherapies will lead to greater patient compliance with therapy regimens.

Another use of the present invention will be in combinations having complementary effects or complementary modes of action. For example, ASBT inhibitors frequently lower LDL lipoprotein but also induce de novo synthesis of cholesterol via upregulation of 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMG-CoA reductase) activity. In contrast, HMG-CoA reductase inhibitors curtail the biosynthesis of cholesterol via inhibition of HMG-CoA reductase. A therapeutic combination of an ASBT inhibitor and a HMG-CoA reductase inhibitor will, when dosages are optimally adjusted, significantly lower LDL and reduce the biosynthesis of new cholesterol. c. ASBT Inhibitors The present invention discloses that treatment of a subject with one or more ASBT inhibitors and one or more cyclooxygenase-2 selective inhibitors results in the prophylaxis and/or treatment of cardiovascular conditions and/or disorders relative to other combination regimens.

The method comprises treating the subject with an amount of an apical sodium co-dependent bile acid transport inhibitor and an amount of a cyclooxygenase-2 selective inhibitor or its prodrug, wherein the amount of the apical sodium co-dependent bile acid transport inhibitor and the amount of the cyclooxygenase-2 selective inhibitor

together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the said compounds.

For example, one of the many embodiments of the present invention is a combination therapy comprising therapeutic dosages of a cyclooxygenase-2 selective inhibitor and a lignan ASBT inhibitor selected from the group of lignan ASBT inhibitors illustrated in Table 2 as compounds A-2 and A-3.

In another embodiment of the invention the ASBT inhibitor is selected from the group of bicyclic benzothiazepine ASBT inhibitors illustrated in Table 2 as compounds A-1, A-4 and A-5, including the diastereomers, enantiomers, racemates, salts, tautomers, conjugate acids, and prodrugs thereof.

In a preferred embodiment of the invention the ASBT inhibitor is selected from the group of benzothiepine ASBT inhibitors having the general Formula I shown below and possessing, by way of example and not limitation, the structures A-6 through A-22 disclosed in Table 2, including the diastereomers, enantiomers, racemates, salts, tautomers, conjugate acids, and prodrugs thereof.

X, Y = H and/or substituted 0, NH

Table 2. Examples of ASBT Inhibitors as Embodiments Compound Number Structural Formula V NH NH . A-2 OCHg H3C0 U A-2 OCH3 I 0 oc3 H3C0 // "OCH3 0 OH Compound Number Structural Formula A-3 OCH3 HO 0 OCH3 LOCH3 H3C0 J'0 OH HO OH H A 4 Co \ S/ Co U OH A-5 p o H3co Cul Cl nu °° N OH OH Compound Number Structural Formula °v C 1- N OH ci- 0 N+ IN 'oH s \ I pCH3PhS03 N v oh u \-% N+ N u '%/ 'OH Compound Number Structural Formula A-10 oX//o s N 'OH CH3SO3 I X CH3 03 C A-11 oX//o s A-22 'OH r--cozy , 'oH ---'-, N N ),'"OH A-1 ,''oH o C°2H C02H Compound Number Structural Formula A-13 oX//o s OH OH Cp2H C02H N N 0 A-14 oX//o s \ oh l, oh CF3CO2 N+CHg A-15 oX//o i s i OH N 'OH tu +-CH3 N H Compound Number Structural Formula A-16N X s N | Z OH lp//\ 0 COSH A-17 NX = lez v ),'oh 1, o ci- o 0, l N (CHZCH3) 2 0\\ CH A-18 N e I\ OU ci- c ; ox Cl- ! (CH2CH3) 2 Compound Number Structural Formula A-19 0 s 'oH NU , ouzo A-2 H s ZOU I,,, U A-20 0 OH Soh N A-2 0 N s N 'OH' N(CH CH) QS BUZZ A-22 0 0 s A-22 OH 'oH OCH3 0 R Nez H N H R = polyethylene glycol (MW = 5000)

The individual patent documents referenced in Table 3 below describe the preparation of the aforementioned ASBT inhibitors of Table 2 and are each herein incorporated by reference.

Table 3. References for Preparation of ASBT Inhibitors Compound Number Patent/Literature Reference for Preparation of Compound Per Se A-1 US 5817652 A-2 Atherosclerosis, 107,247-257 (1994) A-3 WO 94/24087 A-4 US 5910494 A-5 WO 99/35135 A-6 US 5994391 A-7 US 5994391 A-8 US 5994391 A-9 US 5994391 A-10 US 5994391 A-11 US 5994391 A-12 US 5994391 A-13 US 5994391 A-14 US 5994391 A-15 US 5994391 A-16 US 5994391 A-17 US 5994391 A-18 US 5994391 A-19 US 5994391 A-20 US 5994391 Compound Number Patent/Literature Reference for Preparation of Compound Per Se A-21 US 5994391 A-22 US 5994391 Another embodiment of the present invention comprises a pharmaceutical combination containing an amount of an apical sodium co-dependent bile acid transport inhibitor and an amount of a cyclooxygenase-2 selective inhibitor or its prodrug, and a pharmaceutically acceptable carrier, wherein the amount of the apical sodium co-dependent bile acid transport inhibitor and the amount of the cyclooxygenase-2 selective inhibitor together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the said compounds. For example, one of the many embodiments of the present invention is a combination comprising therapeutic dosages of an ASBT inhibitor selected from Table 2 and a cyclooxygenase-2 selective inhibitor selected from Tables 4,6 and 7A below. A preferred embodiment of the present invention is a combination comprising therapeutic dosages of a benzothiepine ASBT inhibitor and a tricyclic cyclooxygenase-2 selective inhibitor. d. Cyclooxygenase Inhibitors The present invention discloses that treatment of a subject with one or more ASBT inhibitors and one or more cyclooxygenase-2 selective inhibitors results in the prophylaxis and/or treatment of cardiovascular conditions and/or disorders. The method comprises treating the subject with an amount of an ASBT inhibitor and an amount of a cyclooxygenase-2 selective inhibitor or its prodrug, wherein the amount of the apical sodium co-dependent bile

acid transport inhibitor and the amount of the cyclooxygenase-2 selective inhibitor together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the said compounds.

For example, one of the many embodiments of the present invention is a combination therapy comprising a therapeutic amount of an ASBT inhibitor and a therapeutic amount of a cyclooxygenase inhibitor. The cyclooxygenase inhibitor can be, by way of example, a COX-2 nonselective inhibitor or a COX-2 selective inhibitor. Examples of COX-2 nonselective inhibitors include the well-known compounds aspirin, acetaminophen, indomethacin, sulindac, etodolac, mefenamic acid, tolmetin, ketorolac, diclofenac, ibuprofen, naproxen, fenoprofen, ketoprofen, oxaprozin, flurbiprofen, piroxicam, tenoxicam, phenylbutazone, apazone, or nimesulide or a pharmaceutically acceptable salt or derivative or prodrug thereof. In a preferred embodiment of the invention the COX-2 nonselective inhibitor is selected from the group comprising aspirin, acetaminophen, indomethacin, ibuprofen, or naproxen.

In another embodiment of the invention the cyclooxygenase inhibitor can be a cyclooxygenase-2 selective inhibitor, for example, the COX-2 selective inhibitor meloxicam, Formula B-1 (CAS registry number 71125-38-7) or a pharmaceutically acceptable salt or derivative or prodrug thereof.

In yet another embodiment of the invention the cyclooxygenase-2 selective inhibitor is the COX-2 selective inhibitor RS 57067, 6-[[5-(4-chlorobenzyl)-1, 4- dimethyl-lH-pyrrol-2-yl] methyl]-3 (2H)-pyridazinone, Formula B-2 (CAS registry number 179382-91-3) or a pharmaceutically acceptable salt or derivative or prodrug thereof.

In a preferred embodiment of the invention the cyclooxygenase-2 selective inhibitor is a COX-2 selective inhibitor of the chromene structural class that is a substituted benzopyran or a substituted benzopyran analog selected from the group consisting of substituted benzothiopyrans, dihydroquinolines, or dihydronaphthalenes having the general Formula II shown below and possessing, by way of example and not limitation, the structures disclosed in Table 4, including the diastereomers, enantiomers, racemates, tautomers, salts, esters, amides and prodrugs thereof.

Table 4. Examples of Chromene COX-2 Selective Inhibitors as Embodiments Compound Number Structural Formula B-3 0 Oh 0 CF3 6-Nitro-2-trifluoromethyl-2H-1 -benzopyran-3-carboxylic acid B-4 O Ci OH 1 oh CHEZ 6-Chloro-8-methyl-2-trifluoromethyl -2H-1-benzopyran-3-carboxylic acid B-5 0 ci SOH O CFg ( (S)-6-Chloro-7- (1, 1-dimethylethyl)-2- (trifluo romethyl-2H-l-benzopyran-3-carboxylicacid Compound Number Structural Formula B-6 0 OH 0 cl3 U L. r 2-Trifluoromethyl-2H-naphtho [2, 3-b] pyran-3-carboxylic acid B-7 0 \ \ OH 0/O--CF 3 6-Chloro-7- (4-nitrophenoxy)-2- (trifluoromethyl)-2H-1- benzopyran-3-carboxylic acid B-8 O Ci OH Cl 0 CF3 ( (S)-6, 8-Dichloro-2- (trifluoromethyl)- 2H-1-benzopyran-3-carboxylic acid B-9 vs - oh 0 ci3 6-Chloro-2- (trifluoromethyl-4-phenyl-2H- l-benzopyran-3-carboxylic acid Compound Number Structural Formula B-1 0 ou HO//0 CF3 6- (4-Hydroxybenzoyl)-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid B-11 0 F3C OH SC S CF3 2-(Trifluoromethyl)-6-[(trifluoromethyl) thio] -2H-1-benzothiopyran-3-carboxylic acid B-12 0 ci - oh S CF3 Cl 6,8-Dichloro-2-trifluoromethyl-2H-1- benzothiopyran-3-carboxylic acid B-13 0 OU S OH 6- (1, 1-Dimethylethyl)-2- (trifluoromethyl) -2H-1-benzothiopyran-3-carboxylic acid Compound Number Structural Formula B-14 F ouOH F H CF3 6,7-Difluoro-l, 2-dihydro-2- (trifluoro methyl)-3-quinolinecarboxylic acid B-15 0 ci CFg Uh3 6-Chloro-l, 2-dihydro-l-methyl-2- (trifluoro methyl)-3-guinolinecarboxylic acid B-16 0 cl OH N N CF3 6-Chloro-2- (trifluoromethyl)-1, 2-dihydro [1, 8]Jnaphthyridine-3-carboxylic acid B-17 0 ce OH ASZ ((S)-6-Chloro-1, 2-dihydro-2-(trifluoro methyl)-3-quinolinecarboxylic acid

The individual patent documents referenced in Table 5 below describe the preparation of the aforementioned COX-2 inhibitors of Table 4 and are each herein incorporated by reference. Table 5. References for Preparation of Chromene COX-2 Inhibitors Compound Number Patent Reference B-3 US 6,077,850; example 37 B-4 US 6,077,850; example 38 B5 US 6,077,850; example 68 B-6 US 6,034,256; example 64 B-7 US 6,077,850; example 203 B-8 US 6,034,256; example 175 B-9 US 6,077,850; example 143 B-10 US 6,077,850; example 98 B-11 US 6,077,850; example 155 B-12 US 6,077,850; example 156 B-13 US 6,077,850; example 147 B-14 US 6,077,850; example 159 B-15 US 6,034,256; example 165 B-16 US 6,077,850; example 174 B-17 US 6,034,256; example 172

In a more preferred embodiment of the invention the cycloxygenase-2 selective inhibitor is the substituted benzopyran (S)-6, 8-dichloro-2- (trifluoromethyl)-2H-l- benzopyran-3-carboxylic acid, Formula B-8, or a pharmaceutically acceptable salt or derivative or prodrug thereof.

In a further preferred embodiment of the invention the cyclooxygenase inhibitor is selected from the class of tricyclic cyclooxygenase-2 selective inhibitors represented by the general structure of Formula III wherein A is a substituent selected from partially unsaturated or unsaturated heterocyclyl and partially unsaturated or unsaturated carbocyclic rings ; wherein RI is at least one substituent selected from heterocyclyl, cycloalkyl, cycloalkenyl and aryl, wherein R1 is optionally substituted at a substitutable position with one or more radicals selected from alkyl, haloalkyl, cyano, carboxyl, alkoxycarbonyl, hydroxyl, hydroxyalkyl, haloalkoxy, amino, alkylamino, arylamino, nitro, alkoxyalkyl, alkylsulfinyl, halo, alkoxy and alkylthio; wherein R2 is methyl or amino; and wherein R3 is a radical selected from hydrido, halo, alkyl, alkenyl, alkynyl, oxo, cyano, carboxyl, cyanoalkyl, heterocyclyloxy, alkyloxy, alkylthio, alkylcarbonyl, cycloalkyl, aryl, haloalkyl, heterocyclyl, cycloalkenyl, aralkyl, heterocyclylalkyl, acyl, alkylthioalkyl, hydroxyalkyl, alkoxycarbonyl, arylcarbonyl, aralkylcarbonyl, aralkenyl, alkoxyalkyl, arylthioalkyl, aryloxyalkyl, aralkylthioalkyl, aralkoxyalkyl, alkoxyaralkoxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, aminocarbonylalkyl, alkylaminocarbonyl, N- arylaminocarbonyl, N-alkyl-N-arylaminocarbonyl,

alkylaminocarbonylalkyl, carboxyalkyl, alkylamino, N- arylamino, N-aralkylamino, N-alkyl-N-aralkylamino, N- alkyl-N-arylamino, aminoalkyl, alkylaminoalkyl, N- arylaminoalkyl, N-aralkylaminoalkyl, N-alkyl-N- aralkylaminoalkyl, N-alkyl-N-arylaminoalkyl, aryloxy, aralkoxy, arylthio, aralkylthio, alkylsulfinyl, alkylsulfonyl, aminosulfonyl, alkylaminosulfonyl, N- arylaminosulfonyl, arylsulfonyl, N-alkyl-N- arylaminosulfonyl; or a pharmaceutically acceptable salt or derivative or prodrug thereof.

In a still more preferred embodiment of the invention the cyclooxygenase-2 selective inhibitor represented by the above Formula III is selected from the group of compounds, illustrated in Table 6, consisting of celecoxib (B-18), valdecoxib (B-19), deracoxib (B-20), rofecoxib (B- 21), etoricoxib (MK-663 ; B-22), JTE-522 (B-23), or a pharmaceutically acceptable salt or derivative or prodrug thereof.

In an even more preferred embodiment of the invention the COX-2 selective inhibitor is selected from the group consisting of celecoxib, rofecoxib and etoricoxib.

Table 6. Examples of Tricyclic COX-2 Selective Inhibitors as Embodiments Compound Number Structural Formula B-18 H N S CHg I's CH3 /N H2 I I CFg Compound Number Structural Formula B-19 ouzo H2N '\N H3C 0/ B-20 0 F s OCH3 NU N CHF2 B-21 0 0 s hic N 0 Nu H C s, / CH3 Cl C1 B-23 S o 3--, < CH3

In another highly preferred embodiment of the invention parecoxib, B-24, which is a therapeutically effective prodrug of the tricyclic cyclooxygenase-2 selective inhibitor valdecoxib, B-19, may be advantageously employed as a source of a cyclooxygenase inhibitor (US 5,932,598, herein incorporated by reference).

The individual patent documents referenced in Table 7 below describe the preparation of the aforementioned cyclooxygenase-2 selective inhibitors B-18 through B-24 and are each herein incorporated by reference.

Table 7. References for Preparation of Tricyclic COX-2 Inhibitors and Prodrugs Compound Number Patent Reference B-18 US 5,466,823 B-19 US 5,633,272 B-20 US 5,521,207 B-21 US 5,840,924 B-22 WO 98/03484 B-23 WO 00/25779 B-24 US 5,932,598

Another embodiment of the present invention comprises a pharmaceutical combination containing an amount of an

apical sodium co-dependent bile acid transport inhibitor and an amount of a cyclooxygenase inhibitor (e. g., cyclooxygenase-2 selective inhibitor) or its prodrug, and a pharmaceutically acceptable carrier, wherein the amount of the apical sodium co-dependent bile acid transport inhibitor and the amount of the cyclooxygenase inhibitor (e. g., cyclooxygenase-2 selective inhibitor) together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the said compounds. For example, one of the many embodiments of the present invention is a combination comprising therapeutic dosages of an ASBT inhibitor selected from the aforementioned Table 2 and a COX-2 selective inhibitor selected from the aforementioned Tables 4,6 and 7A. A preferred embodiment of the present invention is a combination containing therapeutic dosages of a benzothiepine ASBT inhibitor and a tricyclic COX-2 selective inhibitor.

Another preferred embodiment of the present invention is a combination containing therapeutic dosages of an ASBT inhibitor selected from Table 2 and a COX-2 selective inhibitor selected from Table 7A below.

Table 7A Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-1 OH NH ce ce [2- (2, 4-Dichloro-6-ethyl-3, 5-dimethyl-phenylamino)- 5-propyl-phenyl]-aceticacid; D-2 CH3 0 HN"IN 0 H3 ci 6-E [5-(4-chlorobenzoyl)-1, 4-dimethyl-lH-pyrrol-2- yl] methyl]-3 (2H)-pyridazinone or RS 57067 D-3 o o OH 6-Nitro-2-trifluoromethyl-2H-1 -benzopyran-3-carboxylic acid Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-4 0 ci or 0-CF Cl CF3 CHUG 6-Chloro-8-methyl-2-trifluoromethyl -2H-1-benzopyran-3-carboxylic acid D-5 0 ci - oh Cl CF3 ( (S)-6-Chloro-7- (1, 1-dimethylethyl)-2- (trifluo romethyl-2H-1-benzopyran-3-carboxylicacid D-6 o OH 0 caf3 2-Trifluoromethyl-2H-naphtho[2,3-b] pyran-3-carboxylicacid D-7 0 'OH O/OCF 3 6-Chloro-7- (4-nitrophenoxy)-2- (trifluoromethyl)-2H-1- benzopyran-3-carboxylicacid ) Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-8 0 ci oh D-8 o Cl ((S)-6, 8-Dichloro-2-(trifluoromethyl)- 2H-1-benzopyran-3-carboxylic acid D-9 0 0 ci - oh OF 3 6-Chloro-2- (trifluoromethyl)-4-phenyl-2H- 1-benzopyran-3-carboxylic acid D-1000 1 OH HO 0 CF3 6- (4-Hydroxybenzoyl)-2- (trifluoromethyl) -2H-1-benzopyran-3-carboxylic acid D-11 0 F3C--s OH sc S CF3 2-(Trifluoromethyl)-6-[(trifluoromethyl) thio] - 2H-1-benzothiopyran-3-carboxylic acid Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-12 ci OH cl C1 6,8-Dichloro-2-trifluoromethyl-2H-l- benzothiopyran-3-carboxylic acid e D-13 ° OU 6- (1, 1-Dimethylethyl)-2- (trifluoromethyl) - 2H-1-benzothiopyran-3-carboxylic acid D-14 °l F I OH F H CF3 6,7-Difluoro-1,2-dihydro-2- (trifluoro methyl)-3-quinolinecarboxylic acid - 15o ci - oh CL, CF-I3 6-Chloro-1, 2-dihydro-1-methyl-2-(trifluoro methyl)-3-quinolinecarboxylic acid t Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-16 0 ci OU N CF3 6-Chloro-2- (trifluoromethyl)-1, 2-dihydro [1,8] naphthyridine-3-carboxylic acid - DTo D-17 0 ci OH ((S)-6-Chloro-1, 2-dihydro-2-(trifluoro methyl)-3-quinolinecarboxylic acid D-18 0\\0 g i ./'I 3 H2N N" NEZ CF3 r celecoxib D-190\\0 "ils Han / 0 H3 C O. valdecoxib D-20 0 0 F H N S/OCH3 han laN N zu CHF2 deracoxib Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-21 0\\ 0 "3c 0 rofecoxib D-22op 9 M N etoricoxib D-23 ouzo HzNi i Y Ozon Cl3 24o JTE-522 D-24 0 HAN zon H3c C (I parecoxib Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-25 0 OH O N F 0 H3C' S O ABT-963 D-26 0 HN 1l ERZ fro nous N02 N02 N-(2-Cyclohexyloxy-4-nitro-phenyl)-methanesulfonamide or NS-398; D-27 O ci OH F 0 'F F 6-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-2 8 ci OH F 0 'F F 6-chloro-7-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carbox ylic acid ; D-29 'OZON 0 F \ F O OU 8- (1-methylethyl)-2-trifluoromethyl-2H-1-benzopyran-3-carboxyl ic acid ; D-30 CUL 0 F F \ Ha HO O 6-chloro-8- (l-methylethyl)-2-trifluoromethyl-2H-1-benzopyran-3-carboxyl ic acid ; Component~2 Name and/or Structure (COX-2 Selective Inhibitor) D-31 [INSERT STRUCTURE] 2-trifluoromethyl-3H-naphthopyran-3-carboxylic acid; D-32 0 OH F F F 7- (1, 1-dimethylethyl)-2-trifluoromethyl-2H-1-benzopyran-3-carboxy lic acid; D-33 Br OH 'F 0 6-bromo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid ; D-34 CI 0"OH 0 FI F \ F O OH 8-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-35 F 0 zou F F 0 F F F F 6-trifluoromethoxy-2-trifluoromethyl-2H-1-benzopyran-3-carbo xylic acid; D-36 Cf O H F ci 0 'F F 5,7-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid ; D-37 0 6 H 0 0 FAF F 8-phenyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-380 OH o 0 F 'F F 7,8-dimethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; D-39 OH F F 0 F F 6,8-bis (dimethylethyl)-2-trifluoromethyl-2H-1-benzopyran-3-carboxyl ic acid; D-40 0 OH I F F F F 7- (1-methylethyl)-2-trifluoromethyl-2H-1-benzopyran-3-carboxyl ic acid ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-41 F F HO 0 0 7-phenyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; D-42 0 ci OH 0 F F 'F F 6-chloro-7-ethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxy lic acid ; D-43 Ci 0 F F \ Ha HO O 6-chloro-8-ethyl-2-trifluoromethyl-2H-I-benzopyran-3-carboxy lic acid ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-44 ci ZON if 0 F \F F 6-chloro-7-phenyl-2-trifluoromethyl-2H-1-benzopyran-3-carbox ylic acid; D-45 ci zou ciao C sOH 'F F 6,7-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; D-46 O ce OH F F 'F CRI 6,8-dichloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-47 F F HO 0 0 2-trifluoromethyl-3H-naptho [2,1-b] pyran-3-carboxylic acid; D-48 0 < OH O 'F cri 8-chloro-6-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carbox ylic acid ; D-49 OH F 0 F 'F CRI 8-chloro-6-methoxy-2-trifluoromethyl-2H-1-benzopyran-3-carbo xylic acid ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-500 Br OH F 'F cri 6-bromo-8-chloro-2-trifluoromethyl-2H-1-benzopyran-3-carboxy lic acid ; D-51 F ZOU F0 F 'F Bar 8-bromo-6-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxy lic acid ; D-52 0 OH IF 0 'F Bar 8-bromo-6-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxy lic acid; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-53 ber FX F F F \ Ho HO O 8-bromo-5-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carboxy lic acid; D-54 ci zou 0 F 0 'F F F 6-chloro-8-fluoro-2-trifluoromethyl-2H-1-benzopyran-3-carbox ylic acid ; D-55 O \ Br I 0 F Ho HO O 6-bromo-8-methoxy-2-trifluoromethyl-2H-1-benzopyran-3-carbox ylic acid ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-56 oXF OH FEZ O OU zu O S zozo NH 6- [ [ (phenylmethyl) amino] sulfonyl]-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid ; D-57 F 0 0 HA HO 0 6- [ (dimethylamino) sulfonyl]-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid ; D-58 0 O { ; OU ho HO son 6- [ (methylamino) sulfonyl]-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-59F F OH OH ouf CN OX s N O 6- [ (4-morpholino) sulfonyl]-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid ; D-60 HN so Po FEZ HO 0 'F F 6- [ (1, 1-dimethylethyl) aminosulfonyl]-2-trifluoromethyl-2H-1-benzopyran-3-carboxyli c acid ; DO 'fuzz F HO I Ho N a on 6- [ (2-methylpropyl) aminosulfonyl]-2-trifluoromethyl-2H-1-benzopyran-3-carboxyli c acid; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-62 F 0 0 HO 0 6-methylsulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxy lic acid ; D-63 H 0 0 N OU F 0 CRI 8-chloro-6-[[(phenylmethyl) amino] sulfonyl]-2-trifluoromethyl-2H-l-benzopyran-3-carboxylic acid; D-64 F 0 0 FQ HO 0 0 6-phenylacetyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxyli c acid; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-650 Br Oh Br 0 F 'F Bar 6,8-dibromo-2-trifluoromethyl-2H-l-benzopyran-3-carboxylic acid; D-66 0 OH F 0 'F CRI 8-chloro-5, 6-dimethyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid ; D-67 ci H 0 F 'F CL 6,8-dichloro-(S)-2-trifluoromethyl-2H-l-benzopyran-3-carboxy lic acid; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-68 F F 0 F I O zozo v v HO 6-benzylsulfonyl-2-trifluoromethyl-2H-1-benzopyran-3-carboxy lic acid; D-69 F 0 0 HA HO N I 0 0 H 6- [[N-(2-furylmethyl) arnino3sulfonyl3-2-trifluoromethyl-2H-1-benzopyran-3-carboxy lic acid; D70 0 0 0 8 OU PO N 0 0 H 6-[[N-(2-phenylethyl) amino3sulfonyl]-2-trifluoromethyl-2H-l-benzopyran-3-carboxyl ic acid; D-710 D-71 O I OH F 0 'F F 6-iodo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylic acid ; component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-72 0 F/ F If O OU 7- (1, 1-dimethylethyl)-2-pentafluoroethyl-2H-1-benzopyran-3-carbox ylic acid; D-73 O ce zou F s 'F F 6-chloro-2-trifluoromethyl-2H-1-benzothiopyran-3-carboxylic acid ; D-744 Me\ 0 _. 0 O C1 BMS-347070 Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-75 0 N nu zon r° i 8-acetyl-3- (4-fluorophenyl)-2- (4-methylsulfonyl) phenyl-imidazo (l, 2-a) pyridine ; D-7 6 n ou _ i 7 O S O--- 5, 5-dimethyl-4- (4-methylsulfonyl) phenyl-3-phenyl-2- (5H)-furanone ; D-77 F F F N N 0 F 5- (4-fluorophenyl)-1- [4- (methylsulfonyl) phenyl]-3- (trifluoromethyl) pyrazole; Component 2Name and/or Structure (COX-2 Selective Inhibitor) D-78 _aN F F 0 \ il F li I s- \ _ 4- (4-fluorophenyl)-5- [4- (methylsulfonyl) phenyl]-1-phenyl-3- (trifluoromethyl)pyrazole; D-79 cl N b-NH2 / /lfonamide ; I 0 4- (5- (4-chlorophenyl)-3- (4-methoxyphenyl)-1H-pyrazol-1-yl) benzenesulfonamide; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-80 N N N H2N 0 °/\ y 4- (3, 5-bis (4-methylphenyl)-1 H-pyrazol-1-yl) benzenesulfonamide ; D-81 N N p \ ci /% o HaN 4-(5-(4-chlorophenyl)-3-phenyl-1 H-pyrazol-1-yl) benzenesulfonamide; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-82/ N N -sud- N zu han han H2N 4- (3, 5-bis (4-methoxyphenyl)-lH-pyrazol-l-yl) benzenesulfonamide ; D-83 N N N ils HAN 2 4- (5- (4-chlorophenyl)-3- (4-methylphenyl)-1H-pyrazol-1-yl) benzenesulfonamide ; component 2 Name and/or Structure (COX-2 Selective Inhibitor) 3-8 4 V V / ( -N+ cl 4-(5-(4-chlorophenyl)-3-(4-nitrophenyl)-1 H-pyrazol-1-yl) benzenesulfonamide; D-85 Cl i 11 //\ I oN ! \ II NH2 CI 4-(5-(4-chlorophenyl)-3-(5-chloro-2-ienyl)-lH-pyrazol-l-yl) benzenesulfonamide; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-86 CI 0 N' II NH Il 2 \N O 4-(4-chloro-3, 5-diphenyl-1 H-pyrazol-1-yl) benzenesulfonamide; Dz F F N N zu HAN HsN H2N 4- [5- (4-chlorophenyl)-3- (trifluoromethyl)-lH-pyrazol-1-yl] benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-88 F 5NH2 N-NH2 N II NH F e _-Ii 2 \N/ O F F 4- [5-phenyl-3- (trifluoromethyl)-lH-pyrazol-1-yl] benzenesulfonamide ; D-89 F F N N ou zu H2N 4- [5- (4-fluorophenyl)-3- (trifluoromethyl)-1 H-pyrazol-1-yl] benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-90 F F F NEZ N% VS zozo HAN 4- [5- (4-methoxyphenyl)-3- (trifluoromethyl)-lH-pyrazol-1-yl] benzenesulfonamide ; D-91 F F NEZ N ri han HgN i H2N 4- [5- (4-chlorophonyl)-3- (difluoromethyl)-lH-pyrazol-1-yl] benzenesulfonamidel Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-92 F F N N O\ s HAN han D-93F F F ZON cri N 0 / NH2 nu2 cl 4- [4-chloro-5- (4-chlorophenyl)-3- (trifluoromethyl)-lH-pyrazol-1-yl] benzenesulfonamide ; v Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-94 F F N N N ZU H2N 4- [3- (difluoromethyl)-5- (4-methylphenyl)-lH-pyrazol-1-yl] benzenesulfonamide ; D-95 0 / N S-NH2 F F 4- [3- (difluoromethyl)-5-phenyl-lH-pyrazol-1-yl] benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-96 F F N N VS zozo HAN 4- [3- (difluo. romethyl)-5- (4-methoxyphenyl)-IH-pyrazol-I-yl) benzenesulfonamide ; D-97 N N N p F /0 O HAN 4- 3-cyano-5- (4-fluorophenyl)-lH-pyrazol-1-yl] benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-98 F F N \ J N /O F V o/\NH2 _. NHO 4- [3- (difluoromethyl)-5- (3-fluoro-4-methoxyphenyl)-lH-pyrazol-1-yl] benzenesulfonamide; Dz F F ZON I /O 0 p \nez zozo 4- [5- (3-fluoro-4-methoxyphenyl)-3- (trifluoromethyl)-lH-pyrazol-1-yl] benzenesulfonamide ; D-100 I cri N 0 Is HAN 4- [4-chloro-5-phenyl-1 benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-101 HO N N N zu won han 4- [5- (4-chlorophenyl)-3- (hydroxyrnethyl)-1H-pyrazol-1-yl] benzenesulfonamide ; D-102 F NAZI Nez O /c/ H2N 4-[5-(4-chlorophenyl)-3-(hydroxymethyl)-lH-pyrazol-l-yl] benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-103 \ S 0 F V F 5- (4-fluorophenyl)-6- [4- (methylsulfonyl) phenyl] spiro [2.4] hept-5-ene ; D-104 1 if O S O NH2 4- [6- (4-fluorophenyl) spiro [2.4] hept-5-en-5-yl] benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-105 0 1 6- (4-fluorophenyl)-7- [4- (methylsulfonyl) phenyl] spiro [3.4] oct-6-ene ; D-106 0 caf 0 0 0 5- (3-chloro-4-methoxyphenyl)-6- [4- (methylsulfonyl) phenyl] spiro [2.4] hept-5-ene; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-107 cri 0 Cl H2N-S H2N I 0 4- [6- (3-chloro-4-methoxyphenyl) spiro [2. 4] hept-5-en-5-yl] benzenesulfonamide ; D-108 , O ci 0 CI O CI 5- (3, 5-dichloro-4-methoxyphenyl)-6- [4- (methylsulfonyl) phenyl] spiro [2.4] hept-5-ene; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-109 F V 0 0 5- (3-chloro-4-fluorophenyl)-6- [4- (methylsulfonyl) phenyl] spiro [2. 4] hept-5-ene ; ci cl CI O H N II O 4- [6- (3, 4-dichlorophenyl) spiro [2.4] hept-5-en-5-yl] benzenesulfonamide ; D-111 N F S cl 1 2- (3-chloro-4-fluorophenyl)-4- (4-fluorophenyl)-5- (4-methylsulfonylphenyl) thiazole; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-112 N 0 cl zu 0 2- (2-chlorophenyl)-4- (4-fluorophenyl)-5- (4-methylsulfonylphenyl) thiazole ; D-113 jet)- N zon zu 5- (4-fluorophenyl)-4- (4-methylsulfonylphenyl)-2-methylthiazole ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-114 po vs F F s F N F F F 4-(4-fluorophenyl)-5-(4-methylsulfonylphenyl)-2-trifluoromet hylthiasole; D-115 po VS S F 4- (4-fluorophenyl)-5- (4-methylsulfonylphenyl)-2- (2-thienyl) thiazole; 4-(4-fluorophenyl)-5-(4-methylsulfonylphenyl)-2-(2-thienyl) thiazole ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) F D-116 N HAN HN zu 0 4- (4-fluorophenyl)-5- (4-methylsulfonylphenyl)-2-benzylaminothiazole ; D-117 po vs F N /S N H 4-(4-fluorophenyl)-5-(4-methylsulfonylphenyl)-2-(1-propylami no) thiazole; D-118 \--N N CRI \S O cul Cl 2- ( (3,5-dichiorophenoxy) methyl)-4- (4-fluorophenyl)-5- [4- (methylsulfonyl) phenyl] thiazole; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-119 s F F I ZON (F /S, O 5- (4-fluorophenyl)-4- (4-methylsulfonylphenyl)-2-trifluoromethylthiazole ; D-120 O-so F 1-methylsulfonyl-4- [1, 1-dimethyl-4- (4-fluorophenyl) cyclopenta-2, 4-dien-3-yl] benzene; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-121 0 H2N II/ H2N-6 F 4- [4- (4-fluorophenyl)-1, 1-dimethylcyclopenta-2, 4-dien-3-yl] benzenesulfonamide ; D-122 \ os F V 5- (4-fluorophenyl)-6- [4- (methylsulfonyi) phenyl] spiro [2.4] hepta-4,6-diene; 5-(4-fluorophenyl)-6-[4-(methylsulfonyl) phenyl3spirof2. 4] hepta-4, 6-diene, Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-123 F O S O NH2 4-[6-(4-fluorophenyl) spirof2. 43hepta-4, 6-dien-5-ylSbenzenesulfonamide; D-1. 24 s zu N N N O N 6- (4-fluorophenyl)-2-methoxy-5- [4- (methylsulfonyl) phenyl]-pyridine-3-carbonitrile; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-125 N Ber N 2-bromo-6- (4-fluorophenyl)-5- [4- (methylsulfonyl) phenyl]-pyridine-3-carbonitrile ; D-126 0 /YY //o 'N N 6- (4-fluorophenyl)-5- [4- (methylsulfonyl) phenyl]-2-phenyl-pyridine-3-carboniixile ; component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-127 N N zon 11 N O F F F 4- [2- (4-methylpyridin-2-yl)-4- (trifluoromethyl)-1 H-imidazol-1-yl] benzenesulfonamide ; D-128//----N 0 III /F FUZZ u F F 4-t2-(5-methylpyridin-3-yl)-4-(trifluoromethyl)-lH-imidazol- I-yl] benzenesulfonamide; D-129 lu Il /F N2N II /N F F F X t sulfonanude ; component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-130 N t N ZON F 0 F F 3-rl-l4-(methylsulfonyl) phenyl]-4-(trifluoromethyl)-lH-imidazol-2-yl] pyridine; D-131 \S/9 F F 0 F X b N N N 2- [1- [4- (methylsulfonyl) phenyl-4- (trifluoromethyl)]-lH-imidazol-2-yl] pyridine ; D-132 0 F F s I F NU N N 2-methyl-4- [1- [4- (methylsulfonyl) phenyl-4- (trifluoromethyl)]-lH-imidazol-2-yl] pyridine ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) 0 NV N s F , N N 2-methyl-6- [1- [4- (methylsulfonyl) phenyl-4- (trifluoromethyl)]-1 H-imidazol-2-yl pyridine ; D-134F F F N N N v /-N oSw\ zu NH2 4- [2- (6-methylpyridin-3-yl)-4- (trifluoromethyl)-lH-imidazol-1-yl] benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-135 F O, s N N F F 2- (3, 4-difluorophenyl)-I- [4- (methyIsulfonyl) phenylj-4- (trifluoromethyl)-IH-imidazole ; D-136 F F F N N po Zu NH2 4- [2- (4-methylphenyl)-4- (trifluoromethyl)-1 H-imidazol-1-yl] benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-137 N N CI N ci 0 2- (4-chlorophenyl)-1- [4- (methylsulfonyl) phenyl]-4-methyl-lH-imidazole ; D-138 N N cinq S' O s t w y Hd. 2 component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-139 Cl\ bA\5% zu N F N 2- (4-chlorophenyl)-4- (4-fluorophenyl)-1- [4- (methylsulfonyl) phenyl]-IH-imidazole ; D-l4 O o 0 NJ F N -0 F 2- (3-fluoro-4-methoxyphenyl)-1- [4- (methylsulfonyl) phenyl-4- (trifluoromethyl)]-IH-imidazole ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-141 0 ZON F F F F 1- [4-(methylsulfonyl) phenyl]-2-phenyl-4-trifluoromethyl-1 H-imidazole ; D-142 F F F N r N ex s 0 2- (4-methylphenyl)-1- [4- (methylsulfonyl) phenyl]-4-trifluoromethyl-1H-imidazole ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-143 ce NH2 \/ N N F IF F 4- [2- (3-chloro-4-methylphenyl)-4- (trifluoromethyl)-1H-imidazol-1-yl] benzenesulfonamide ; D-l44 s N N F IF F 2- (3-fluoro-5-methylphenyl)-l- [4- (methylsulfonyl) phenyl]-4- (trifluoromethyl)-lH-imidazole ; D-145 \ NN2 s N N F IF F 4- [2- (3-fluoro-5-methylphenyl)-4- (tzifluoronlethyl)-IH-imidazol-I-yl] benzenesuifonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-146 0 ZON F F 0 2- (3-methylphenyl)-1- [4- (methylsulfonyl) phenyl]-4-trifluoromethyl-1 H-imidazole ; D-14 7 0 un F H2P4-8 N 11 F F F 4- [2- (3-methylphenyl)-4-trifluoromethyl-lH-imidazol-1-yl] benzenesulfonamide ; D-148 i ce 0 N N Lui-- my F F 1- [4- (methylsulfonyl) phenyl]-2- (3-chlorophenyl)-4-trifluoromethyl-lH-imidazole ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-149 Ci 0 Vif F H2N II N O F F 4- [2- (3-chlorophenyl)-4-trifluoromethyl-1H-imidazol-1-yl] benzenesulfonamide ; D-150 O N H2N O N < 11 / F F F F 4- [2-phenyl-4-trifluoromethyl-1 H-irnidazol-1-yl] benzenesulfonamide ; D-151 o NH o N F N F F F 4- [2- (4-methoxy-3-chlorophenyl)-4-trifluoromethyl-lH-imidazol-1-y l] benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-152 XXFF tir F F F F / F I-allyl-4-(4-fluorophenyl)-3-f4-(methylsulfonyl) phenylS-5-(trifluoromethyl)-lH-pyrazole; D-153/\NJ Hin zon 0 nu N F F 4- [l-ethyl-4- (4-fluorophenyl)-5- (trifluoromethyl)-lH-pyrazol-3-yl] benzenesulfonamide ; D-154 by A NJX F F H F4 N F F F F N-phenyl- [4- (4-fluorophenyl)-3- [4- (medrylsulfonyl) phenyl]-5- (Mfluoromethyl)-1H-pyrazoI-1-yI] acetamide; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) o 1//F oo su fuzz N FEZ F 1 F ethyl [4- (4-fluorophenyl)-3- [4- (methylsulfonyl) phenyl]-5- (trifluoromethyl)-lH-pyrazol-1-yl] acetate; D-156 OeN k--, N/ N zon 0 -\1 4- (4-fluorophenyl)-3- [4- (mathylsulfonyl) phenyl]-1- (2-phenylethyl)-1H-pyrazole ; D-157 ou su N NEZ F N F F F 4- (4-fluorophenyl)-3- [4- (methylsulfonyl) phenyl]-1- (2-phenylethyl)-5- (trifluoromethyl) pyrazole ; 4 4 ~ 9 T hylOpyazole, Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-158 s/ F 0 NJ F \ F F F 1-ethyl-4-(4-fluorophenyl)-3- [4- (methylsulfonyl) phenyl]-5- (trifluoromethyl)-IH-pyrazole ; D-159 O S O F N F NU F F F 5- (4-fluorophenyl)-4- (4-methylsulfonylphenyl)-2-trifluoromethyl-lH-imidazole ; component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-160 o S O N NU NU if 4- [4- (methylsulfonyl) phenyl]-5- (2-thiophenyl)-2- (trifluoromethyl)-lH-imidazole ; D-161 F F 'F O F F F N F v 5- (4-fluorophenyl)-2-methoxy-4- [4- (methylsulfonyl) phenyl]-6- (trifluoromethyl) pyridine ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-162 F F F N zu 0 2-ethoxy-5- (4-fluorophenyl)-4- [4- (methylsulfonyl) phenyl]-6- (trifluoromethyl) pyridine ; Dog s F F' r 5- (4-fluorophenyl)-4- [4- (methylsulfonyl) phenyl]-2- (2-propynyloxy)-6- (trifluoromethyl) pyridine ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-164 F 'F Br F o 2-bromo-5- (4-fluorophenyl)-4- [4- (methylsulfonyl) phenyl]-6- (trifluoromethyl) pyridine ; D-165 F 0 NU2 cri cri /O 4- [2- (3-chloro-4-methoxyphenyl)-4, 5-difluorophenyl] benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-166 O S O F /,/ 1- (4-fluorophenyl)-2- [4- (methylsulfonyl) phenyl] benzene ; Dz F 6 N 0 s o 5-difluoromethyl-4- (4-methylsulfonylphenyl)-3-phenylisoxazole ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-168 JAZZ zon N Hin 4- [3-ethyl-5-phenylisoxazol-4-yl] benzenesulfonamide ; Dz F 0 ZON 0 H2N6 O 4- [5-difluoromethyl-3-phenylisoxazol-4-yl] benzenesulfonamide ; D-170 OH 0 ZON 0 \ , ° Han 4- [5-hydroxymethyl-3-phenylisoxazol-4-yl] benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-171 0 zon N H2N \ E b H2N \\ \ 4- [5-methyl-3-phenyl-isoxazol-4-yl] benzenesulfonamide ; D-172 ou S 4 F F 1- [2- (4-fluorophenyl) cyclopenten-1-yl]-4- (methylsulfonyl) benzene ; D-173 ou S\ F F 1 1- [2- (4-fluoro-2-methylphenyl) cyclopenten-1-yl]-4- (methylsulfonyl) benzene; 1-[2-(4-fluoro-2-methylphenyl) cyclopenten-l-yl]-4-(methylSulsonyl) benzene ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-174 O, _ ci CI 1- [2- (4-chlorophenyl) cyclopenten-1-yl]-4- (methylsulfonyl)benzene; D-175/ z ci cri CI 1 CI 1- [2- (2,4-dichlorophenyl) cyclopenten-1-yl]-4- (methylsulfonyl) benzene; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) ----/ Zu S F F F F 1-[2-(4-trifluoromethylphenyl) cyclopenten-1-yl] 4-(methylsulfonyl) benzene; D-177 f d po s 1- [2- (4-methylthiophenyl) cyclopenten-1-yl]-4- (methylsulfonyl)benzene; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-178. 0 s F F 1-r2-(4-fluorophenyl)-4, 4-dimethylcyclopenten-1-yl]-4-(methylsulfonyl) benzene; D-179 0 Han s F F lcnyl)-4, 4-d z thlyclopenten-l-yl] benzenesifon2sude ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-180 zu ci 1- [2- (4-chlorophenyl)-4, 4-dimethylcyclopenten-1-ylJ-4- (methylsulfonyl) benzene ; D-181 O H2N \sfl ci 0 4- [2- (4-chlorophenyl)-4, 4-dimethylcyclopenten-1-yl] benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-182 NH2 s 4- [2- (4-fluorophenyl) cyclopenten-1-yl] benzenesulfonamide ; D-13 NH2 °V 0 cl v 4- [2- (4-chlorophenyl) cyclopenten-1-yl] benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) a _ : z N u a and/or Strucorc (OX-2 Seleetive hlhibitor) n D-184 0 .-/° e o 1- [2- (4-methoxyphenyl) cyclopenten-1-yl]-4- (methylsulfonyl) benzene ; D-185 F /// //\ /O 1- [2-(2, 3-difluorophenyl) cyclopenten-1-yl]-4-(methylsulfonyl) benzene ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-186NHz zu PO zu O 4- [2- (3-fluoro-4-methoxyphenyl) cyclopenten-1-yl] benzenesulfonamide ; D-187/ O S/ po cri O 1-[2-(3-chloro-4-methoxyphenyl) cyclopenten-1-yll-4-(methylsulfonyl) benzene; component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-188NH2 /M% ° CI F 4- [2- (3-chloro-4-fluorophenyl) cyclopenten-1-yl] benzenesulfonamide ; D-189 NH2 O\/ C N 4- [2- (2-methylpyridin-5-yl) cyclopenten-1-yl] benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-190 F o 0 0 ethyl 2- 4- (4-fluorophenyl)-5- [4- (methylsulfonyl) phenyl] oxazol-2-yl]-2-benzyl-acetate ; D-191 su 0 = O OH ZON 2- [4- (4-fluorophenyl)-5- [4- (methylsulfonyl) phenyl] oxazol-2-yl] acetic acid ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-192 N N 0 S zu 2- (tert-butyl)-4- (4-fluorophenyl)-5- [4- (methylsulfonyl) phenyl] oxazole ; D-l93 po vs 0 ex F _N I s 4- (4-fluorophenyl)-5- [4- (methylsulfonyl) phenyl]-2-phenyloxazole; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-194 D-194 N I o zu s 4- (4-fluorophenyl)-2-methyl-5- [4- (methylsulfonyl) phenyl] oxazole; D-195 F 0 F, N F X NH2 4- [5- (3-fluoro-4-methoxyphenyl)-2-trifluoromethyl-4-oxazolyl] benzenesulfonamide ; D-196 0 ce OH F _o F F 6-chloro-7-(l, l-dimethylelyl)-2-trifluoromethyl-2H-l-berszopyraIl-3-carbox ylic acid ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-197 ce OH F o 'F F 6-chloro-8-methyl-2-trifluoromethyl-2H-1-benzopyran-3-carbox ylic acid; D-198 5,5-dimethyl-3- (3-fluorophenyl)-4- (4-methyl- sulphonyl-2 (5H)-fluranone; D-199 O ce OH F s 'F F 6-chloro-2-trifluoromethyl-2H-1-benzothiopyran-3-carboxylic acid ; D-200 F F F N N cl /c O HaN 4- [5- (4-chlorophenyl)-3- (trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide ; component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-201 F F N N 0. H2N 4- [5- (4-methylphenyl)-3- (trifluoromethyl)-1 H-pyrazol-1-yl] benzenesulfonamide ; D-202 F F ZON I S\ p \NH2 zozo 4- [5- (3-fluoro-4-methoxyphenyl)-3- (difluoromethyl)-lH-pyrazol-1-yl] benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-2 03 gN w NS- ZON -S N F F F 3- [1- [4- (methylsulfonyl) phenyl]-4-trifluoromethyl-IH-imidazol-2-ylpyridine ; D-204 F F N N N O rs o 2-methyl-5- [l- [4- (methylsulfonyl) phenyl]-4-trifluoromethyl-lH-imidazol-2-yl] pyridine ; D-205 0 Zon HzN IS N (F / O F F 4- [2- (5-methylpyridin-3-yl)-4- (trifluoromethyl)-1 H-imidazol-1-yl] benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-206 0 zon N H2N \\ O 4- [5-methyl-3-phenylisoxazol-4-yl] benzenesulfonamide ; D-207 OH 0 ZON 0 H2N \ han 4- [5-hydroxymethyl-3-phenylisoxazol-4-yl] benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-208 D-208 F 0 F F HO I F O S O [2-trifluoromethyl-5- (3, 4-difluorophenyl)-4-oxazolyl] benzenesulfonamide ; D-209 H2N po 0 14 4- [2-methyl-4-phenyl-5-oxazolyl] benzenesulfonamide ; D-210 4- [5- (3-fluoro-4-methoxyphenyl-2-trifluoromethyl)-4- oxazolyl] benzenesulfonamide ; Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-211 \ CH Cl H N H3C F H3C/F [2- (2-Chloro-6-fluoro-phenylamino)-5-methyl-phenyl]-acetic acid or COX 189 or Lumiracoxib D-212 O HN/I I CH3 HNS II HAN 0 NO2 N-(4-Nitro-2-phenoxy-phenyl)-methanesulfonamide or Nimesulide component 2 Name and/or Structure (COX-2 Selective Inhibitor) co pow t 2 Nan e andbor S ; (COX-2 Seleetive Inhibitor) D-213 F F 0 0 HN O S O N-[6-(2, 4-Difluoro-phenoxy)-l-oxo-inden-5-yl]-methanesulfonamide orFlosulide D-214 I F 0 nua-N Na+-N N-[6-(2, 4-Difluoro-phenylsulfanyl)-l-oxo-lH-inden-5-yl]-methanesulfo namide, soldium salt, or T ; 745337 D-215 Ó t F 0 s N- [5- (4-fluoro-phenylsulfanyl)-thiophen-2-yl]-methanesulfonamide or RWJ-63556 component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-216 L-784512 HaN S JAZZ HZN S HAN oh (5Z)-2-amino-5-f [3, 5-bis (l, 1-dimethylethyl)-4-hydroxyphenyl] methylene]-4 (5H)-thiazolone or Darbufelone D-218 CS-502 D-219 LAS-34475 D-220 LAS-34555 D-221 S-33516 D-222 SD-8381 D-223 L-783003; component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-224 NH 0 0 0 w// o i N- [3- (formylamino)-4-oxo-6-phenoxy-4H-I-benzopyran-7-ylJ-methanes ulfonamide or T614 D-225 D-1367 D-226 L-748731 D-227 _ po HA' 0 qH y H ho (6aR, l0aR)-3- (1, 1-dimethylheptyl)-6a, 7,10, 10a-tetrahydro-l-hydroxy-6, 6-dimethyl-6H-dibenzo [b, d] pyran-9-ca rboxylic acid or CT 3 CT3 D-228 CGP-28238 Component 2 Name and/or Structure (COX-2 Selective Inhibitor) D-229 Ha \O zozo O 4- [ [3, 5-bis (1, 1-dimethylethyl)-4-hydroxyphenyl] methylene] dihydro-2-methyl-2H-1, 2-oxazin-3 (4H)-one or BF-389 D-230 GR-253035 D-231 6-dioxo-9H-purin-8-yl-cinnamic acid D-232 S-2474

Further, according to another embodiment of the present invention, in combination with an ASBT inhibitor of Table 2, the COX-2 selective inhibitors noted above (Table 7A) may be selected from D-1, D-2, D-3, D-4, D-5, D-6, D-7, D-8, D-9, D-10, D-11, D-12, D-13, D-14, D-15, D- 16, D-17, celecoxib (D-18), D-19, D-20, rofecoxib (D-21), D-22, D-23, D-24, D-25, D-26, D-27, D-28, D-29, D-30, D- 31, D-32, D-33, D-34, D-35, D-36, D-37, D-38, D-39, D-40, D-41, D-42, D-43, D-44, D-45, D-46, D-47, D-48, D-49, D- 50, D-51, D-52, D-53, D-54, D-55, D-56, D-57, D-58, D-59, D-60, D-61, D-62, D-63, D-64, D-65, D-66, D-67, D-68, D- 69, D-70, D-71, D-72, D-73, D-74, D-75, D-76, D-77, D-78, D-79, D-80, D-81, D-82, D-83, D-84, D-85, D-86, D-87, D- 88, D-89, D-90, D-91, D-92, D-93, D-94, D-95, D-96, D-97, D-98, D-99, D-100, D-101, D-102, D-103, D-104, D-105, D- 106, D-107, D-108, D-109, D-110, D-111, D-112, D-113, D- 114, D-115, D-116, D-117, D-118, D-119, D-120, D-121, D- 122, D-123, D-124, D-125, D-126, D-127, D-128, D-129, D- 130, D-131, D-132, D-133, D-134, D-135, D-136, D-137, D- 138, D-139, D-140, D-141, D-142, D-143, D-144, D-145, D- 146, D-147, D-148, D-149, D-150, D-151, D-152, D-153, D- 154, D-155, D-156, D-157, D-158, D-159, D-160, D-161, D- 162, D-163, D-164, D-165, D-166, D-167, D-168, D-169, D- 170, D-171, D-172, D-173, D-174, D-175, D-176, D-177, D- 178, D-179, D-180, D-181, D-182, D-183, D-184, D-185, D- 186, D-187, D-188, D-189, D-190, D-191, D-192, D-193, D- 194, D-195, D-196, D-197, D-198, D-199, D-200, D-201, D- 202, D-203, D-204, D-205, D-206, D-207, D-208, D-209, D- 210, D-211, D-212, D-213, D-214, D-215, D-216, D-217, D- 218, D-219, D-220, D-221, D-222, D-223, D-224, D-225, D- 226, D-227, D-228, D-229, D-230, D-231, D-232, or an isomer, a pharmaceutically acceptable salt, ester, or prodrug thereof. Even further, according to another embodiment of the present invention, in combination with the ASBT inhibitors of Table 2, the COX-2 selective inhibitors noted above (Table 7A) may be selected from D-1

to D-5, D-6 to D-10, D-11 to D-15, D-16 to D-20, D-21 to D-25, D-26 to D-30, D-31 to D-35, D-36-D-40, D-41 to D-45, D-46 to D-50, D-51 to D-55, D-56 to D-60, D-61 to D-65, D- 66 to D-70, D-71 to D-75, D-76 to D-80, D-81 to D-85, D- D-86 to D-90, D-91 to D-95, D-96 to D-100, D-101 to D-105, D-106 to D-110, D-111 to D-115, D-116 to D-120, D-121 to D-125, D-126 to D-130, D-131 to D-135, D-136 to D-140, D- 141 to D-145, D-146 to D-150, D-151 to D-155, D-156 to D- 160, D-161 to D-165, D-166 to D-170, D-171 to D-175, D-176 to D-180, D-181 to D-185, D-186 to D-190, D-191 to D-195, D-196 to D-200, D-201 to D-205, D-206 to D-210, D-211 to D-215, D-216 to D-220, D-221 to D-225, D-226 to D-230, D- 231-D-232 or combinations thereof. e. HMG-CoA Reductase Inhibitors The present invention discloses that treatment of a subject with one or more ASBT inhibitors, one or more cyclooxygenase-2 selective inhibitors and one or more HMG- CoA reductase inhibitors results in the prophylaxis and/or treatment of cardiovascular conditions and/or disorders relative to other combination regimens. The method comprises treating the subject with an amount of an ASBT inhibitor, an amount of a cyclooxygenase-2 selective inhibitor or its prodrug and an amount of an HMG-CoA inhibitor, wherein the amount of the ASBT inhibitor, the amount of the cyclooxygenase-2 selective inhibitor and the amount of the HMG-CoA inhibitor together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the said compounds.

For example, one of the many embodiments of the present invention is a combination therapy comprising therapeutic dosages of an ASBT inhibitor described above, therapeutic dosages of a cyclooxygenase-2 selective inhibitor described above and therapeutic dosages of an HMG-CoA reductase inhibitor as herein provided.

HMG Co-A reductase inhibitors encompassing a wide range of structures are useful in the methods and combinations of the present invention. Such HMG Co-A reductase inhibitors may be, for example, statins that have been synthetically or semi-synthetically prepared, statins extracted from natural sources such as plants, or statins isolated as fungal metabolites from cultures of suitable microorganisms. Nonlimiting examples of HMG Co-A reductase inhibitors that may be used in the present invention include those HMG Co-A reductase inhibitors disclosed by way of example and not limitation in Table 8, including the diastereomers, enantiomers, racemates, salts, tautomers, conjugate acids, and prodrugs thereof.

The therapeutic compounds of Table 8 can be used in the present invention in a variety of forms, including acid form, salt form, racemates, enantiomers, zwitterions, and tautomers.

Table 8. Examples of HMG-CoA Reductase Inhibitors as Embodiments Compounds and CAS Numbers for Compound Classes Specific and Reference Representative Compounds Benfluorex 23602-78-0 ES 474498, Servier Fluvastatin 93957-54-1 EP 244364, Sandoz Lovastatin 75330-75-5 EP 22478, Merck & Co. Pravastatin 81093-37-0 DE 3122499, Sankyo Simvastatin 79902-63-9 EP 33538, Merck & Co. Atorvastatin 134523-00-5 EP 409281, Warner- Lambert Cerivastatin 145599-86-6 JP 08073-432, Bayer Bervastatin 132017-01-7 EP 380392, Merck KGaA Compounds and CAS Numbers for Compound Classes Specific and Reference Representative Compounds Rosuvastatin 147098-20-2 US 5260440, Shionogi (ZD-4522) Itavastatin 141750-63-2 WO 97/23200, Kowa Dalvastatin 132100-55-1 Kuttar et al., J. Chromatogr., A 678, 259-63 (1994); Rhone- Poulenc Rorer Mevastatin 73573-88-3 JP 56051992 ; Sankyo ZD 9720 WO 97/06802 ZD 4522 147098-20-2 EP 521471; Bioorg. (calcium salt); Med. Chem., 5,437-444 147098-18-8 (1997) ; Drugs Future, (sodium salt) 24,511-513 (1999) BMS 180431 129829-03-4 Sit et al., J. Med. Chem., 33, 2982-99 (1990) ; Bristol-Myers Squibb NK 104 141750-63-2 Takano et al., Tetahedron: Assymetry, 4,201-4 (1993); Nissan Chemical Compounds and CAS Numbers for Compound Classes Specific and Reference Representative Compounds (Carboxydihydroxy-148966-78-3,139 EP 464845; Shionogi heptenyl)-993-44-5,139993 sulfonylpyrroles,-45-6,139993- including S 4522 46-7,139993-47- 8,139993-48-9, 139 993-49-0, 139993-50-3,139 993-51-4,139993 - 52-5, 139993-53 -6, 139 993-54- 7,139993-55-8, 139993-56-9,139 993-57-0,139993 -58-1, 139993- 59-2,139993-60- 5,139993-61-6, 139993-62-7,139 993-63-8,139 993-64-9,139 993-65-0,139993 -66-1, 139993-67 - 2, 139993-68-3, 139993-69-4,139 993-70-7,139993 -71-8, 139993-72 - 9, 139993-73-0, 139 993-74-1, 139993-75-2, 139993-76-3, 139993-77-4,139 993-78-5, 139993 -79-6, 139993-80 -9, 140110-63-0, 140128-98-9, 140 128-99-0, 140157 - 62-6 Boron analogs of di-125894-01-1, 125 Sood et al., Eur. J. and tripeptides 894-02-2,125894 Med. Chem., 25, 301-8 -03-3, 125894-04 (1990) ; Boron -4, 125894-05-5, Biologicals 125894-08-8, 125 894-09-9,125914 -96-7 Zaragozic Acids 157058-13-4,157 GB 2270312 058-14-5,157058 -15-6, 157058-16 - 7, 157058-17-8, 157058-18-9,157 058-19-0 Compounds and CAS Numbers for Compound Classes Specific and Reference Representative Compounds Seco-oxysterol 157555-28-7, Larsen et al., J. Med. analogs, including U 157-555-29-8 Chem., 37,2343-51 88156 (1994) ; Pharmacia & Upjohn Pyridopyrimidines, 64405-40-9, Hermecz et al., Hung. including acitemate 101197-99-3 Arzneim-Forsch., 29, 1833-5 (1979); Mitsubishi BMS 22566 129829-03-4 Sit et al., J. Med. Chem., 33, 2982-99 (1990) ; Bristol- Meyers-Squibb Colestolone 50673-97-7 Raulston et al., Biochem. Biophys. Res. Commun., 71, 984-9 (1976) ; American Home Products CP 83101 130746-82-6, Wint and McCarthy, J. 130778-27-7 Labelled Compd. Radiopharm., 25,1289- 97 (1988); Pfizer Dihydromevinolin 77517-29-4 Falck and Yang, Tetrahedron Lett., 25, 3563-66 (1984) ; Merck & Co. DMP 565 Ko et al., Abstr. Papers Am. Chem. Soc. (207t''Nat. Meeting, Part 1, MEDI 10, (1994) ; Dupont Merck Pyridyl and 122254-45-9 Beck et al., J. Med. Pyrimidinylethenyl-Chem., 33,52-60 desmethylmevalonates (1990) ; Hoechst Marion including glenvastin Roussel GR 95030 157243-22-6 US 5316765 ; Glaxo Wellcome Isoxazolopyridyl-130581-42-9, 130 EP 369323 mevalonates, 581-43-0, 130 carboxylic acids and 581-44-1, 130 esters 581-45-2, 130 581-46-3, 130 581-47-4, 130 581-48-5, 130 581-49-6, 130 581-50-9,130 581-51-0,130 81-52-1, 130619- 07-7,130619-08- 8,130619-09-9 Compounds and CAS Numbers for Compound Classes Specific and Reference Representative Compounds Lactones of 6-127502-48-1, Jenderella et al., J. phenoxy-3,5- 13606-66-1, Med. Chem., 34,2962- dihydroxy-hexanoic 136034-04-3 83 (1991); Hoechst acids Marion Roussel L 659699 29066-42-0 Chiang et al., J. Org. Chem., 54, 5708-12 (1989) ; Merck & Co. L 669262 130468-11-0 Stokker, J. Org. Chem., 59, 5983-6 (1994); Merck & Co. Pannorin 137023-81-5 Ogawa et al., J. Antibiot., 44,762-7 (1991) ; Toyoko Noko Univ Rawsonol 125111-69-5 Cane et al., Phytochemistry, 28, 2917-19 (1989); SmithKline Beecham RP 61969 126059-69-6 EP 326386; Phone- Poulenc Rorer Bile acid-derived Kramer et al., HMG Co-A reductase Biochim. Biophys. inhibitors; Na S Acta, 1227, 137-54 2467 and S 2468 (1994); Hoechst Marion Roussel SC 32561 76752-41-5 US 4230626; Monsanto SC 45355 125793-76-2 EP 329124; non- industrial source Phosphorus-133983-25-2 US 5274155; Bristol- containing HMG Co-A Myers Squibb reductase inhibitors including SQ 33600 6-Aryloxymethyl-4-135054-71-6, 136 EP 418648 hydroxytetrahydro-215-82-2,136 pyran-2-ones, car-215-83-3,136215 boxylic acids and-84-4,136215- salts 85-5,136315-18- 9,136315-19-0, 136315-20-3, 136 315-21-4,136316 -20-6 Atorvastatin calcium 134523-03-8 Baumann et al., (CI 981) Tetrahedron Lett., 33, 2283-4 (1992). Mevinolin analogs EP 245003 Pyranone derivatives US 4937259 Compounds and CAS Numbers for Compound Classes Specific and Reference Representative Compounds 1,2,4-Triazolidine-16044-43-2 WO 9000897 3,5-diones Isoazolidine-3,5- 124756-24-7 EP 321090 diones CS 514 81181-70-6 DE 3122499 1, 10-Bis (carboxy-32827-49-9 DE 2038835 methylthio) decane α, ß-, and γ- Huang and Hall, Eur. Alkylaminophenone J. Med. Chem., 31, analogs, including 281-90 (1996) N-phenyl-piperazino- propiophenone 3-Amino-1-(2, 3,4- Huang and Hall, Arch. mononitro-, mono-or Pharm., 329,339-346 dihalophenyl) propan- (1996) 1-ones, including 3- morpholino-or piperidino-1- (3- nitrophenyl)-propan- 1-ones Substituted 64769-68-2 US 4049813 isoxazolo pyridinones Biphenyl derivatives JP 07089898 4- [1- (Substituted Watanabe et al., Eur. phenyl)-2-oxopyr-J. Med. Chem., 29, rolidin-4-yl] meth-675-86 (1994) oxybenzoic acids Dihydroxy (tetra- US 5134155 hydro-indazolyl, tetrahydrocyclo- pentapyrazolyl, or hexahydrocyclohepta- pyrazole) heptenoate derivatives A 1233 Kitasato University BAY-w-9533 Bayer BB 476 British Biotech BMS180436 Bristol-Myers Squibb Chiral HMG Co-A Chiroscience reductase inhibitors Compounds and CAS Numbers for Compound Classes Specific and Reference Representative Compounds Isoxazolopyridine Nissan Chemical HMG Co-A reductase inhibitors Seco-oxysterol HMG Pharmacia & Upjohn Co-A reductase inhibitors Thiophene HMG Co-A Sandoz reductase inhibitors HMG Co-A reductase Hoechest Marion inhibitors, 6-phen-Roussel oxy-3, 5-dihydroxy- hexanoic acids N-((1-Methylpropyl)-Sandoz carbonyl)-8- (2- (tetrahydro-4-hydr- oxy-6-oxo-2H-pyran- 2-yl) ethyl)-per- hydroisoquinoline N- (l-Oxododecyl)- Hoechst Marion Roussel 4a, 10-dimethyl-8- aza-trans-deca-3Pol P 882222 Nissan Chemical S 853758A Hoechst Marion Roussel (S)-4-((2-(4-(4-Flu-Bristol-Myers Squibb orophenyl)-5-methyl- 2- (1-methyl ethyl)-6- phenyl-3-pyridinyl)- ethenyl) hydroxyphos- phinyl)-3-hydroxy- butanoic acid, disodium salt SDZ 265859 Sandoz (4R-(4α, 6ß (E)))-6- Warner Lambert (2- (5- (4-Fluoro- phenyl)-3- (1--methyl- ethyl)-1-(2- pyridinylpyrazol-4- yl) ethenyl) tetra- hydro-4-hydroxy-2H- pyran-2-one 5ß-aminoethyl-Boehringer Mannheim thiopentanoic acid derivatives 6-Amino-2-mercapto-North Carolina 5-methylpyrimidine-University 4-carboxylic acid Compounds and CAS Numbers for Compound Classes Specific and Reference Representative Compounds 6-Phenoxymethyl-and Hoechst Marion Roussel 6-phenylethylen--(4- hydroxy- tetrahydropyran-2- one) analogues

In a preferred embodiment of the present invention the HMG-CoA reductase inhibitors are described in Table 9 below. The individual patent documents referenced in Table 9 describe the prepraration of these statins and are each herein incorporated by reference.

In an even more preferred embodiment of the invention the HMG-CoA inhibitor is selected from the group of statins consisting of atorvastatin, simvastatin, pravastatin, lovastatin, rosuvastatin and itavastatin.

Table 9. References for Preparation of HMG-CoA Reductase Inhibitors Compound Common Name CAS Registry Patent/Literature Number Number Reference for Preparation of Compound Per Se C-1 Fluvastatin 93957-54-1 US 4739073; US 5354772 C-2 Lovastatin 75330-75-5 US 4231938 C-3 Pravastatin 81093-37-0 US 4346227 C-4 Simvastatin 79902-63-9 US 4444784 C-5 Atorvastatìn 134523-00-5 EP 409281, US 5273995 C-6 Cerivastatin 145599-86-6 US 5177080 C-7 Bervastatin 132017-01-7 EP 380392 C-8 Rosuvastatin 147098-20-2 US 5260440 C-9 Itavastatin 141750-63-2 WO 97/23200, Kowa

Another embodiment of the present invention comprises a therapeutic combination containing an amount of an apical sodium co-dependent bile acid transport inhibitor, an amount of a cyclooxygenase-2 selective inhibitor or its prodrug and an amount of an HMG-CoA reductase inhibitor, and a pharmaceutically acceptable carrier, wherein the amount of the apical sodium co-dependent bile acid transport inhibitor, the amount of the cyclooxygenase-2 selective inhibitor and the amount of the HMG-CoA inhibitor together constitute a hypercholesterolemia- related condition effective amount or an inflammation- related condition effective amount of the said compounds.

For example, one of the many embodiments of the present invention is a combination comprising therapeutic dosages of an ASBT inhibitor selected from Table 2, a cyclooxygenase-2 selective inhibitor selected from Tables 4,6 and 7A and an HMG-CoA inhibitor selected from Table 8 or Table 9. A preferred embodiment of the present invention is a combination comprising therapeutic dosages of a benzothiepine ASBT inhibitor, a tricyclic cyclooxygenase-2 selective inhibitor and a statin HMG-CoA inhibitor. f. Dosages, Formulations, and Routes of Administration Many of the compounds useful in the present invention can have at least two asymmetric carbon atoms, and therefore include racemates and stereoisomers, such as diastereomers and enantiomers, in both pure form and in admixture. Such stereoisomers can be prepared using conventional techniques, either by reacting enantiomeric starting materials, or by separating isomers of compounds of the present invention. Isomers may include geometric isomers, for example cis-isomers or trans-isomers across a double bond. All such isomers are contemplated among the

compounds useful in the present invention. The compounds useful in the present invention also include tautomers.

The compounds useful in the present invention as discussed below include their salts, solvates and prodrugs.

The combinations of the present invention can be administered for the prophylaxis and treatment of hyperlipidemic and cardiovascular diseases or conditions by any means, preferably oral, that produce contact of these compounds with their site of action in the body, for example in the ileum of a mammal, e. g., a human.

For the prophylaxis or treatment of the conditions referred to above, the compounds useful in the combinations and methods of the present invention can be used as the compound per se. Pharmaceutically acceptable salts are particularly suitable for medical applications because of their greater aqueous solubility relative to the parent compound. Such salts must clearly have a pharmaceutically acceptable anion or cation. Suitable pharmaceutically acceptable acid addition salts of the compounds of the present invention when possible include those derived from inorganic acids, such as hydrochloric, hydrobromic, phosphoric, metaphosphoric, nitric, sulfonic, and sulfuric acids, and organic acids such as acetic, benzenesulfonic, benzoic, citric, ethanesulfonic, fumaric, gluconic, glycolic, isothionic, lactic, lactobionic, maleic, malic, methanesulfonic, succinic, toluenesulfonic, tartaric, and trifluoroacetic acids. The chloride salt is particularly preferred for medical purposes. Suitable pharmaceutically acceptable base salts include ammonium salts, alkali metal salts such as sodium and potassium salts, and alkaline earth salts such as magnesium and calcium salts.

The anions useful in the present invention are, of course, also required to be pharmaceutically acceptable and are also selected from the above list.

The compounds useful in the present invention can be presented with an acceptable carrier in the form of a pharmaceutical combination. The carrier must, of course, be acceptable in the sense of being compatible with the other ingredients of the combination and must not be deleterious to the recipient. The carrier can be a solid or a liquid, or both, and is preferably formulated with the compound as a unit-dose combination, for example, a tablet, which can contain from 0.05% to 95% by weight of , the active compound. Other pharmacologically active substances can also be present, including other compounds of the present invention. The pharmaceutical combinations of the invention can be prepared by any of the well known techniques of pharmacy, consisting essentially of admixing the components.

These compounds can be administered by any conventional means available for use in conjunction with pharmaceuticals, either as individual therapeutic compounds or as a combination of therapeutic compounds.

The amount of compound which is required to achieve the desired biological effect will, of course, depend on a number of factors such as the specific compound chosen, the use for which it is intended, the mode of administration, and the clinical condition of the recipient.

In general, a total daily dose of an ASBT inhibitor can be in the range of from about 0.01 to about 20 mg/day, preferably from about 0.1 to about 10 mg/day, more preferably from about 0.5 to about 5.0 mg/day.

A total daily dose of a cyclooxygenase-2 selective inhibitor can be in the range of from about 0.3 to about

100 mg/kg body weight/day, preferably from about 1 to about 50 mg/kg body weight/day, more preferably from about 3 to about 10 mg/kg body weight/day.

A total daily dose of an HMG-CoA reductase inhibitor can generally be in the range of from about 0.1 to about 100 mg/day in single or divided doses. Lovastatin, atorvastatin, or mevastatin, for example, generally are each administered separately in a daily dose of about 10 to about 80 mg/day. Fluvastatin is generally administered in a daily dose of about 20 to about 40 mg/day.

Cerivastatin is generally administered in a daily dose of about 0.1 to about 0.3 mg/day.

The daily doses described in the preceding paragraphs for the various therapeutic compounds can be administered to the patient in a single dose, or in proportionate multiple subdoses. Subdoses can be administered 2 to 6 times per day. Doses can be in sustained release form effective to obtain desired results.

In the case of pharmaceutically acceptable salts, the weights indicated above refer to the weight of the acid equivalent or the base equivalent of the therapeutic compound derived from the salt.

Oral delivery of the combinations of the present invention can include formulations, as are well known in the art, to provide prolonged or sustained delivery of the drug to the gastrointestinal tract by any number of mechanisms. These include, but are not limited to, pH sensitive release from the dosage form based on the changing pH of the small intestine, slow erosion of a tablet or capsule, retention in the stomach based on the physical properties of the formulation, bioadhesion of the dosage form to the mucosal lining of the intestinal tract, or enzymatic release of the active drug from the dosage form. For some of the therapeutic compounds useful in the

present invention (e. g., ASBT inhibitors), the intended effect is to extend the time period over which the active drug molecule is delivered to the site of action (e. g., the ileum) by manipulation of the dosage form. Thus, enteric-coated and enteric-coated controlled release formulations are within the scope of the present invention. Suitable enteric coatings include cellulose acetate phthalate, polyvinylacetate phthalate, hydroxypropylmethylcellulose phthalate and anionic polymers of methacrylic acid and methacrylic acid methyl ester.

The combinations of the present invention can be delivered orally either in a solid, in a semi-solid, or in a liquid form. When in a liquid or in a semi-solid form, the combinations of the present invention can, for example, be in the form of a liquid, syrup, or contained in a gel capsule (e. g., a gel cap).

When administered intravenously, the dose for an ASBT inhibitor can, for example, be in the range of from about 0.01 mg to about 20 mg/day, preferably from about 0.1 to about 10 mg/day, more preferably from about 0.5 to about 5.0 mg/day.

For a cyclooxygenase-2 selective inhibitor the intravenously administered dose can, for example, be in the range of from about 0.003 to about 1. 0 mg/kg body weight/day, preferably from about 0.01 to about 0.75 mg/kg body weight/day, more preferably from about 0.1 to about 0.6 mg/kg body weight/day.

An HMG-CoA reductase inhibitor can be intravenously administered, for example, in the range of from about 0.03 to about 5.0 mg/kg body weight/day, preferably from about 0.1 to about 1.0 mg/kg body weight/day, more preferably from about 0.4 to about 0.6 mg/kg body weight/day.

The dose of any of these therapeutic compounds can be conveniently administered as an infusion of from about 10 ng/kg body weight to about 100 ng/kg body weight per minute. Infusion fluids suitable for this purpose can contain, for example, from about 0.1 ng to about 10 mg, preferably from about 1 ng to about 10 mg per milliliter.

Unit doses can contain, for example, from about 1 mg to about 10 g of the compound of the present invention.

Thus, ampoules for injection can contain, for example, from about 1 mg to about 100 mg.

Pharmaceutical combinations according to the present invention include those suitable for oral, rectal, topical, buccal (e. g., sublingual), and parenteral (e. g., subcutaneous, intramuscular, intradermal, or intravenous) administration, although the most suitable route in any given case will depend on the nature and severity of the condition being treated and on the nature of the particular compound which is being used. In most cases, the preferred route of administration is oral.

Pharmaceutical combinations suitable for oral administration can be presented in discrete units, such as capsules, cachets, lozenges, or tablets, each containing a predetermined amount of at least one therapeutic compound useful in the present invention; as a powder or granules; as a solution or a suspension in an aqueous or non-aqueous liquid; or as an oil-in-water or water-in-oil emulsion.

As indicated, such combinations can be prepared by any suitable method of pharmacy which includes the step of bringing into association the active compound (s) and the carrier (which can constitute one or more accessory ingredients). In general, the combinations are prepared by uniformly and intimately admixing the active compound with a liquid or finely divided solid carrier, or both, and then, if necessary, shaping the product. For example,

a tablet can be prepared by compressing or molding a powder or granules of the compound, optionally with one or more accessory ingredients. Compressed tablets can be prepared by compressing, in a suitable machine, the compound in a free-flowing form, such as a powder or granules optionally mixed with a binder, lubricant, inert diluent and/or surface active/dispersing agent (s). Molded tablets can be made by molding, in a suitable machine, the powdered compound moistened with an inert liquid diluent.

Pharmaceutical combinations suitable for buccal (sub- lingual) administration include lozenges comprising a compound of the present invention in a flavored base, usually sucrose, and acacia or tragacanth, and pastilles comprising the compound in an inert base such as gelatin and glycerin or sucrose and acacia.

Pharmaceutical combinations suitable for parenteral administration conveniently comprise sterile aqueous preparations of a compound of the present invention. These preparations are preferably administered intravenously, although administration can also be effected by means of subcutaneous, intramuscular, or intradermal injection.

Such preparations can conveniently be prepared by admixing the compound with water and rendering the resulting solution sterile and isotonic with the blood. Injectable combinations according to the invention will generally contain from 0.1 to 5% w/w of a compound disclosed herein.

Pharmaceutical combinations suitable for rectal administration are preferably presented as unit-dose suppositories. These can be prepared by admixing a compound of the present invention with one or more conventional solid carriers, for example, cocoa butter, and then shaping the resulting mixture.

Pharmaceutical combinations suitable for topical application to the skin preferably take the form of an

ointment, cream, lotion, paste, gel, spray, aerosol, or oil. Carriers which can be used include petroleum jelly (e. g., Vaseline), lanolin, polyethylene glycols, alcohols, and combinations of two or more thereof. The active compound is generally present at a concentration of from 0. 1 to 50% w/w of the combination, for example, from 0.5 to 2%.

Transdermal administration is also possible.

Pharmaceutical combinations suitable for transdermal administration can be presented as discrete patches adapted to remain in intimate contact with the epidermis of the recipient for a prolonged period of time. Such patches suitably contain a compound of the present invention in an optionally buffered, aqueous solution, dissolved and/or dispersed in an adhesive, or dispersed in a polymer. A suitable concentration of the active compound is about 1% to 35%, preferably about 3% to 15%.

As one particular possibility, the compound can be delivered from the patch by electrotransport or iontophoresis, for example, as described in Pharmaceutical Research, 3, 318 (1986).

In any case, the amount of active ingredient that can be combined with carrier materials to produce a single dosage form to be administered will vary depending upon the host treated and the particular mode of administration.

The solid dosage forms for oral administration including capsules, tablets, pills, powders, gel caps, and granules noted above comprise one or more compounds useful in the present invention admixed with at least one inert diluent such as sucrose, lactose, or starch. Such dosage forms may also comprise, as in normal practice, additional substances other than inert diluents, e. g., lubricating agents such as magnesium stearate or solubilizing agents

such as cyclodextrins. In the case of capsules, tablets, powders, granules, gel caps, and pills, the dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings.

Liquid dosage forms for oral administration can include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs containing inert diluents commonly used in the art, such as water. Such combinations may also comprise adjuvants, such as wetting agents, emulsifying and suspending agents, and sweetening, flavoring, and perfuming agents.

Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or setting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, and isotonic sodium chloride solution.

In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed including synthetic mono-or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables.

Pharmaceutically acceptable carriers encompass all the foregoing and the like.

In combination therapy, administration of two or more of the therapeutic agents useful in the present invention may take place sequentially in separate formulations, or may be accomplished by simultaneous administration in a single formulation or separate formulations.

Administration may be accomplished by oral route, or by intravenous, intramuscular, or subcutaneous injections.

The formulation may be in the form of a bolus, or in the form of aqueous or non-aqueous isotonic sterile injection solutions or suspensions. These solutions c-and suspensions may be prepared from sterile powders or granules having one or more pharmaceutically-acceptable carriers or diluents, or a binder such as gelatin or hydroxypropylmethyl cellulose, together wn th one or more of a lubricant, preservative, surface active or dispersing agent.

For oral administration, the pharmaceutical combination may be in the form of, for example, a tablet, capsule, suspension, or liquid. Capsules, tablets, etc., can be prepared by conventional methods well known in the art. The pharmaceutical combination is. preferably made in the form of a dosage unit containing particular amount of the active ingredient or ingredients. Examples of dosage units are tablets or capsules. These may with advantage contain one or more therapeutic compound in an amount described above. For example, in the case of an HMG Co-A reductase inhibitor, the dose range may be from about 0. 01 mg to about 500 mg or any other dose, dependent upon the specific inhibitor, as is I-nown in the art.

The active ingredients may also be administered by injection as a combination wherein, for example, saline, dextrose, or water may be used as c-a suitable carrier. A suitable daily dose of each active therapeutic compound ts one that achieves the same blood Serum level as produced- by oral administration as described above.

The therapeutic compounds nta-y further be administered by any combination of oral/oral, oral/parenteral, or parenteral/parenteral route.

Pharmaceutical combinations for use in the treatment methods of the present invention may be administered in oral form or by intravenous administration. Oral administration of the combination therapy is preferred.

Dosing for oral administration may be with a regimen calling for single daily dose, or for a single dose every other day, or for multiple, spaced doses throughout the day. The therapeutic compounds which make up the combination therapy may be administered simultaneously, either in a combined dosage form or in separate dosage forms intended for substantially simultaneous oral administration. The therapeutic compounds which make up the combination therapy may also be administered sequentially, with either therapeutic compound being administered by a regimen calling for two-step ingestion.

Thus, a regimen may call for sequential administration of the therapeutic compounds with spaced-apart ingestion of the separate, active agents. The time period between the multiple ingestion steps may range from a few minutes to several hours, depending upon the properties of each therapeutic compound such as potency, solubility, bioavailability, plasma half-life and kinetic profile of the therapeutic compound, as well as depending upon the effect of food ingestion and the age and condition of the patient. Circadian variation of the target molecule concentration may also determine the optimal dose interval. The therapeutic compounds of the combined therapy whether administered simultaneously, substantially simultaneously, or sequentially, may involve a regimen calling for administration of one therapeutic compound by oral route and another therapeutic compound by intravenous route. Whether the therapeutic compounds of the combined therapy are administered by oral or intravenous route, separately or together, each such therapeutic compound

will be contained in a suitable pharmaceutical formulation of pharmaceutically-acceptable excipients, diluents or other formulations components. Examples of suitable pharmaceutically-acceptable formulations containing the therapeutic compounds for oral administration are given above. g. Treatment Regimen The dosage regimen to prevent, give relief from, or ameliorate a disease condition having hyperlipidemia and/or inflammation as an element of the disease, e. g., atherosclerosis, or to protect against or treat plaque inflammation or high-cholesterol plasma or blood levels with the compounds and/or combinations of the present invention is selected in accordance with a variety of factors. These include the type, age, weight, sex, diet, and medical condition of the patient, the severity of the disease, the route of administration, pharmacological considerations such as the activity, efficacy, pharmacokinetics and toxicology profiles of the particular compound employed, whether a drug delivery system is utilized, and whether the compound is administered as part of a drug combination. Thus, the dosage regimen actually employed may vary widely and therefore deviate from the preferred dosage regimen set forth above.

Initial treatment of a patient suffering from a hyperlipidemic condition can begin with the dosages indicated above. Treatment should generally be continued as necessary over a period of several weeks to several months or years until the hyperlipidemic disease condition has been controlled or eliminated. Patients undergoing treatment with the compounds or combinations disclosed herein can be routinely monitored by, for example, measuring serum LDL and total cholesterol levels by any of

the methods well known in the art, to determine the effectiveness of the combination therapy. Continuous analysis of such data permits modification of the treatment regimen during therapy so that optimal effective amounts of each type of therapeutic compound are administered at any point in time, and so that the duration of treatment can be determined as well. In this way, the treatment regimen/dosing schedule can be rationally modified over the course of therapy so that the lowest amount of the therapeutic compounds which together exhibit satisfactory effectiveness is administered, and so that administration is continued only so long as is necessary to successfully treat the hyperlipidemic condition.

A potential advantage of the combination therapy disclosed herein may be reduction of the amount of any individual therapeutic compound, or all therapeutic compounds, effective in treating hyperlipidemic conditions such as atherosclerosis and hypercholesterolemia.

One of the several embodiments of the present invention comprises a combination therapy comprising the use of an amount of an ASBT inhibitor and an amount of a cyclooxygenase inhibitor, wherein the amount of the ASBT inhibitor and the amount of the cyclooxygenase inhibitor together comprise an anti-hyperlipidemic condition effective amount or an anti-inflammatory condition effective amount of the ASBT inhibitor and the cyclooxygenase inhibitor. For example, one of the many embodiments of the present invention is a combination therapy comprising therapeutic dosages of an ASBT inhibitor and a cyclooxygenase-2 selective inhibitor. A preferred embodiment of the present invention is a combination therapy comprising therapeutic dosages of a

benzothiepine ASBT inhibitor and a tricyclic cyclooxygenase-2 selective inhibitor.

Another embodiment of the present invention comprises a therapeutic combination containing an amount of an ASBT inhibitor, an amount of a cyclooxygenase-2 selective inhibitor or its prodrug, and a pharmaceutically acceptable carrier, wherein the amount of the ASBT inhibitor, the amount of the cyclooxygenase-2 selective inhibitor together constitute a hypercholesterolemia- related condition effective amount or an inflammation- related condition effective amount of the ASBT inhibitor and the cyclooxygenase inhibitor. For example, one of the many embodiments of the present invention is a combination comprising therapeutic dosages of an ASBT inhibitor and a COX-2 selective inhibitor. A preferred embodiment of the present invention is a combination containing therapeutic dosages of a benzothiepine ASBT inhibitor and a tricyclic COX-2 selective inhibitor.

Another embodiment of the present invention is a combination therapy comprising an amount of an ASBT inhibitor, an amount of a cyclooxygenase-2 selective inhibitor and an amount of an HMG-CoA inhibitor, wherein the amount of the ASBT inhibitor, the amount of the cyclooxygenase-2 selective inhibitor and the amount of the HMG-CoA inhibitor together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the said compounds. For example, one of the many embodiments of the present invention is a combination comprising therapeutic dosages of an ASBT inhibitor, a COX-2 selective inhibitor and an HMG-CoA inhibitor. A preferred embodiment of the present invention is a combination containing therapeutic dosages of a benzothiepine ASBT

inhibitor, a tricyclic COX-2 selective inhibitor and a statin HMG-CoA inhibitor.

Another embodiment of the present invention comprises a therapeutic combination containing an amount of an ASBT inhibitor, an amount of a cyclooxygenase-2 selective inhibitor or its prodrug and an amount of an HMG-CoA reductase inhibitor, and a pharmaceutically acceptable carrier, wherein the amount of the ASBT inhibitor, the amount of the cyclooxygenase-2 selective inhibitor or its prodrug and the amount of the HMG-CoA reductase inhibitor together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the said compounds. For example, one of the many embodiments of the present invention is a combination comprising therapeutic dosages of an ASBT inhibitor, a COX-2 selective inhibitor and an HMG-CoA inhibitor. A preferred embodiment of the present invention is a combination containing therapeutic dosages of a benzothiepine ASBT inhibitor, a tricyclic COX-2 selective inhibitor and a statin HMG-CoA inhibitor.

In a further embodiment, the present invention provides a method for treating or preventing a hypercholesterolemia-related or an inflammation-related condition in a subject in need of such treatment or prevention, comprising treating the subject with an amount of an apical sodium co-dependent bile acid transport inhibitor, an amount of a chromene cyclooxygenase inhibitor (e. g., a chromene COX-2 selective inhibitor) or its prodrug, wherein the amount of the apical sodium co- dependent bile acid transport inhibitor, the amount of the chromene cyclooxygenase inhibitor (e. g., a chromene COX-2 selective inhibitor) together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the

apical sodium co-dependent bile acid transport inhibitor and the chromene cyclooxygenase inhibitor (e. g., a chromene COX-2 selective inhibitor).

In a further embodiment, the present invention provides a method. for treating or preventing a hypercholesterolemia-related or an inflammation-related condition in a subject in need of such treatment or prevention, comprising treating the subject with an amount of an HMG Co-A reductase inhibitor, an amount of a chromene cyclooxygenase inhibitor (e. g., a chromene COX-2 selective inhibitor) or its prodrug, wherein the amount of the HMG Co-A reductase inhibitor and the amount of the chromene cyclooxygenase inhibitor (e. g., a chromene COX-2 selective inhibitor) together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the HMG Co-A reductase inhibitor and the chromene cyclooxygenase inhibitor (e. g., a chromene COX-2 selective inhibitor).

The present invention also provides a method for treating or preventing a hypercholesterolemia-related or an inflammation-related condition in a subject in need of such treatment or prevention, comprising treating the subject with an amount of an HMG Co-A reductase inhibitor and an amount of a source of valdecoxib, wherein the amount of the HMG Co-A reductase inhibitor and the amount of the source of valdecoxib together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the HMG Co-A reductase inhibitor and the source of valdecoxib.

Preferably the source of valdecoxib is valdecoxib.

However, the source of valdecoxib can advantageously be a prodrug of valdecoxib, for example parecoxib.

The embodiments of the present invention can comprise a combination therapy using two or more of the therapeutic compounds described or incorporated herein. The combination therapy can comprise two or more therapeutic compounds having a similar effect from different classes of chemistry, e. g., benzopyran cyclooxygenase-2 selective inhibitors can be therapeutically combined with tricyclic cyclooxygenase-2 selective inhibitors. Therapeutic combinations can also comprise more than two therapeutic compounds. For example, the therapy can comprise the use of an ASBT inhibitor, a cyclooxygenase-2 selective inhibitor, and an HMG-CoA reductase inhibitor.

Alternatively, two or more compounds from the same therapeutic class of chemistry can comprise the therapy, e. g. a combination therapy comprising two or more benzothiepine ASBT inhibitors or two or more tricyclic cyclooxygenase-2 selective inhibitors. h. Kits The present invention further comprises kits that are suitable for use in performing the methods of treatment and/or prophylaxis described above. In one embodiment, the kit contains a first dosage form comprising one or more of the ASBT inhibitors identified in Table 2 and a second dosage form comprising a COX-2 nonselective inhibitor in quantities sufficient to carry out the methods of the present invention. In a more preferred embodiment the kit contains a first dosage form comprising one or more of the ASBT inhibitors identified in Table 2 and a second dosage form comprising a COX-2 selective inhibitor in quantities sufficient to carry out the methods of the present invention. In a still more preferred embodiment the kit contains a first dosage form comprising one or more of the ASBT inhibitors identified

in Table 2 and a second dosage form comprising a COX-2 selective chromene inhibitor identified in Table 4. In an even more highly preferred embodiment the kit contains a first dosage form comprising one or more of the ASBT inhibitors identified in Table 2 and a second dosage form comprising a COX-2 selective tricyclic inhibitor identified in Tables 6 and 7A. In a particularly preferred embodiment, the kit contains a first dosage form comprising the bezothiepine ASBT inhibitor A-8 identified in Table 2 and a second dosage form comprising either celecoxib (B-18) or rofecoxib (B-21).

In another embodiment the kit contains a first dosage form comprising one or more of the ASBT inhibitors identified in Table 2 and a second dosage form comprising a COX-2 nonselective inhibitor and a third dosage form comprising an HMG-CoA reductase inhibitor in quantities sufficient to carry out the methods of the present invention. In a more preferred embodiment the kit contains a first dosage form comprising one or more of the ASBT inhibitors identified in Table 2 and a second dosage form comprising a COX-2 selective inhibitor and a third dosage form comprising an HMG-CoA reductase inhibitor in quantities sufficient to carry out the methods of the present invention. In a still more preferred embodiment the kit contains a first dosage form comprising one or more of the ASBT inhibitors identified in Table 2 and a second dosage form comprising a COX-2 selective chromene inhibitor identified in Table 4 and a third dosage form comprising an HMG-CoA reductase inhibitor. In an even more highly preferred embodiment the kit contains a first dosage form comprising one or more of the ASBT inhibitors identified in Table 2 and a second dosage form comprising a COX-2 selective tricyclic inhibitor identified in Table 6 and a third dosage form comprising an HMG-CoA reductase

inhibitor. In a particularly preferred embodiment the kit comprises a first dosage form comprising the bezothiepine ASBT inhibitor A-8 identified in Table 2 and a second dosage form comprising either celecoxib (B-18) or rofecoxib (B-21) and a third dosage form comprising a statin HMG-CoA reductase inhibitor selected from the group consisting of atorvastatin, simvastatin, pravastatin, lovastatin, rosuvastatin and itavastatin. i. Biological Assays of Utility The utility of the combinations of the present invention can be shown by the following assays. Assays are performed in vitro and in animal models using procedures well recognized to show the utility of the present invention.

In Vitro Assay of Compounds That Inhibit Recombinant COX-1 and/or COX-2 Activity a. Preparation of Recombinant COX Baculoviruses Recombinant COX-1 and COX-2 are prepared as described by Gierse et al. (J. Biochem., 305,479-484 (1995). A 2.0 kb fragment containing the coding region of either human or murine COX-1 or human or murine COX-2 is cloned into a BamH1 site of the baculovirus transfer vector pVL1393 (Invitrogen) to generate the baculovirus transfer vectors for COX-1 and COX-2 in a manner similar to the method of D. R. O'Reilly et al. (Baculovirus Expression Vectors: A Laboratory Manual (1992). Recombinant baculoviruses are isolated by transfecting 4 pg of baculovirus transfer vector DNA into SF9 insect cells (2x108) along with 200 ng of linearized baculovirus plasmid DNA by the calcium phosphate method (M. D. Summers and G. E Smith, A Manual of Methods for Baculovirus Vectors and Insect Cell Culture Procedures, Texas Agric. Exp. Station Bull. 1555 (1987)).

Recombinant viruses are purified by three rounds of plaque purification, and high-titer (107-108 pfu/mL) stocks of virus were prepared. For large-scale production, SF9 insect cells are infected in 10-liter fermentors (0.5xl06/mL) with the recombinant baculovirus stock such that the multiplicity of the infection was 0.1. After 72 hours the cells are centrifuged, and the cell pellet homogenized in Tris/Sucrose (50 mM: 25%, pH 8.0) containing 1% 3- [ (3)-cholamidopropyl) dimethylammonio]-l- propanesulfonate (CHAPS). The homogenate is centrifuged at 10,000 x G for 30 minutes, and the resulting supernatant is stored at-80° C before being assayed for COX activity. b. Assay for COX-1 and COX-2 Activity COX activity is assayed as PGE2 formed/jg protein/time using an ELISA to detect the prostaglandin released.

CHAPS-solubilized insect cell wall membranes containing the appropriate COX enzyme are incubated in a potassium phosphate buffer (50 mM, pH 8.0) containing epinephrine, phenol, and heme with the addition of arachidonic acid (10 , uM). Compounds are pre-incubated with the enzyme for 10- 20 minutes prior to the addition of arachidonic acid. Any reaction between the arachidonic acid and the enzyme is stopped after 10 minutes at 37°C/room temperature by transferring 40 AL of reaction mix into 160 AL ELISA buffer and 25 MM indomethacin. The PGE2 formed will be measured by standard ELISA technology (Cayman Chemical). c. Rapid assay for COX-1 and COX-2 Activity COX activity is assayed as PGE2 formed protein/time using an ELISA to detect the prostaglandin released.

CHAPS-solubilized insect cell wall membranes containing the appropriate COX enzyme are incubated in a potassium phosphate buffer (50 mM potassium phosphate, pH 7.5,300MM epinephrine, 2 NM phenol, 1, uM heme) with the addition of

20 AL of 100 uM arachidonic acid (10 uM). Compounds are pre-incubated with the enzyme for 10 minutes at 37° C prior to the addition of arachidonic acid. Any reaction between the arachidonic acid and the enzyme is stopped after 2 minutes at 37°C/room temperature by transferring 40 AL of reaction mix into 160 AL ELISA buffer and 25, uM indomethacin. The PGE2 formed is measured by standard ELISA technology (Cayman Chemical).

In'Vivo Assay of Anti-inflammatory Compounds in the Rat Carageenan Foot Pad Edema Test The carageenan foot edema test for the in vivo evaluation of anti-inflammatory potency will be as performed essentially as described by Winter et al. (Proc.

Soc. Exp. Biol. Med., 111, 544 (1962). Male Sprague- Dawley rats are selected in each group having average body weights as close as possible. Rats are fasted with free access to water for over sixteen hours prior to the test.

The rats are dosed orally (1 mL) with compounds suspended in vehicle containing 0.5% methylcellulose and 0.025% surfactant, or with vehicle alone. One hour later a subplantar injection of 0.1 mL of 1% solution of carrageenan/sterile 0.9% saline is administered, and the volume of the foot is measured with a displacement plethysmometer connected to a pressure transducer with a digital indicator. Three hours after the injection of the carrageenan the volume of the foot is again measured. The average foot swelling in a group of drug-treated animals is compared with that of a group of plecebo-treated animals, and the percentage inhibition of edema is determined (Otterness and Bliven, Laboratory Models for Testing NSAIDs, in Non-steroidal Anti-Inflammatory Drugs, J. Lombardino, ed., 1985).

In Vitro Assay of Compounds That Inhibit ASBT-mediated Uptake of [14C] Taurocholate (TC) in H14 Cells Baby hamster kidney cells (BHK) transfected with the cDNA of human ASBT (H14 cells) are seeded at 60,000 cells/well in 96-well Top-Count tissue culture plates for assays to be run within in 24 hours of seeding, at 30,000 cells/well for assays run within 48 hours, and at 10,000 cells/well for assays run within 72 hours.

On the day of assay, the cell monolayer is gently washed once with 100 Al assay buffer (Dulbecco's Modified Eagle's medium with 4.5 g/L glucose + 0.2% (w/v) fatty acid free-bovine serum albumin (FAF) BSA). To each well 50 AL of a two-fold concentrate of test compound in assay buffer is added along with 50 AL of 6 M [, 14C] taurocholate in assay buffer (final concentration of 3 [14C] taurocholate). The cell culture plates are incubated for two hours at 37° C prior to gently washing each well twice with 100 AL of Dulbecco's phosphate-buffered saline (PBS) at 4° C containing 0.2% (w/v) (FAF) BSA. The wells are then gently washed once with 100 HL of PBS at 4°C without (FAF) BSA. To each well 200 AL of liquid scintillation counting fluid is added, and the plates are heat sealed and shaken for 30 minutes at room temperature prior to measuring the amount of radioactivity in each well on a Packard Top-Count instrument.

In Vitro Assay of Compounds That Inhibit Uptake of lt4C] Alanine The alanine uptake assay is to be performed in an identical fashion to the taurocholate assay, with the exception that [14C]-labeled alanine was substituted for the radiolabelled taurocholate.

In Vivo Assay of Compounds That Inhibit Rat Ileal Uptake of [14C] Taurocholate into Bile (The method to be used is similar to that described by Une at al.,"Metabolism of 3 «, 7ß-dihydroxy-7a-methyl-5ß- cholanoic acid and 3 «, 7ß-dihydroxy-7a-methyl-5ß-cholanoic acid in hamsters,"Biochim. Biophys. Acta, 833,196-202 (1985).) Male wistar rats (200-300 g) are anesthetized with inactin 8100 mg/kg. Bile ducts are cannulated with a 10" length of PE10 tubing. The small intestine is exposed and laid out on a gauze pad. A cannula (tapered female adapter with 1/8"luer lock) is inserted at 12 cm from the junction of the small intestine and the cecum. A slit is cut at 4 cm from this same junction (utilizing a 8 cm length of ileum). Warm Dulbecco's phosphate buffered saline (PBS) at pH 6.5 (20 mL) is used to flush out the intestinal segment. The distal opening is cannulated with a 20 cm length of silicone tubing (0.02n I. D. x 0.037" O. D.). The proximal cannula is connected to a peristaltic pump and the intestine is washed for 20 minutes with warm PBS at 0.25 mL/min. The temperature of the gut segment is monitored continuously. At the start of the experiment, 2.0 mL of control sample (r14C] taurocholate @ 0.05 mCi/mL, diluted with 5 mM unlabelled taurocholate) is loaded into the gut segment using a 3-mL syringe, and bile sample collection is begun. Control sample is infused at a rate of 0.25 mL/min for 21 minutes. Bile sample fractions are collected for radioassay every three minutes for the first 27 minutes of the procedure. After 21 minutes of sample infusion, the ileal loop is washed out with 20 mL of warm PBS (using a 30-mL syringe), and the loop is further washed out for 21 minutes with warm PBS at 0.25 mL/min. A second perfusion is then initiated as described above, but with test compound being simultaneously administered as

well (21 minutes of administration followed by 21 minutes of washout), and bile is sampled every 3 minutes for the first 27 minutes. If necessary, a third perfusion is performed as above using the control sample.

Measurement of Rat Hepatic Cholesterol Concentration (HEPATIC CHOL) Rat liver tissue is weighed and homogenized in chloroform: methanol (2: 1). After homogenization and centrifugation the supernatant is separated and dried under nitrogen. The residue is dissolved in isopropanol and the cholesterol content is measured enzymatically, using a combination of cholesterol oxidase and peroxidase, as described by Allain et al., Clin. Chem., 20,470 (1974).

Measurement of Rat Hepatic HMG-CoA Reductase Activity Rat liver microsomes are prepared by homogenizing liver samples in a phosphate/sucrose buffer, followed by centrifugal separation. The final pelleted material is resuspended in buffer and an aliquot is assayed for HMG- CoA reductase activity by incubating for 60 minutes at 37° C in the presence of [14C] HMG-CoA (Dupont-NEN). The reaction is stopped by adding 6N HCl followed by centrifugation. An aliquot of the supernatant is subjected to separation using thin-layer chromatography, and the spot corresponding to the enzymatic product is scraped off the plate, extracted and assayed for radioactivity by scintillation counting (Akerlund and Bjorkhem, J. Lipid Res., 31,2159 (1990).

Determination of Rat Serum Cholesterol (SER. CHOL, HDL- CHOL, TGI and VLDL + LDL) Total rat serum cholesterol (SER. CHOL) is measured enzymatically using a commercial kit from Wako Fine Chemicals (Richmond, VA); Cholesterol Cll, Catalog No.

276-64909. HDL cholesterol (HDL-CHOL) is assayed using this same kit after precipitation of VLDL and LDL with Sigma Chemical Co. HDL cholesterol reagent, Catalog No.

352-3 (dextran sulfate method). Total serum triglycerides (blanked) (TGI) are assayed enzymatically with Sigma Chemical Co. GPO-Trinder, Catalog No. 337-B. VLDL and LDL (VLDL + LDL) cholesterol concentrations are calculated as the difference between total and HDL cholesterol.

Measurement of Rat Hepatic Cholesterol 7-a-Hydroxylase Activity (7a-HOase) Rat liver microsomes are prepared by homogenizing liver samples in a phosphate/sucrose buffer, followed by centrifugal separation. The final pelleted material is resuspended in buffer and an aliquot is assayed for cholesterol 7-a-hydroxylase activity by incubating for 5 minutes at 37° C in the presence of NADPH. Following extraction into petroleum ether, the organic solvent is evaporated and the residue is dissolved in acetonitrile/ methanol. The enzymatic product will be separated by injecting an aliquot of the extract onto a C18 reverse- phase HPLC column and quantitating the eluted material using UV detection at 240nm. (Horton et al., J. Clin.

Invest., 93,2084 (1994)).

In Vivo Rat Gavage ASBT Assay Male Wister rats (275-300g) are administered ASBT inhibitors using an oral gavage procedure. Drug or vehicle (0.2% Tween 80 in water) is administered once a

day (9: 00-10: 0 a. m.) for 4 days at varying dosages in a final volume of 2 mL per kilogram of body weight. Total fecal samples are collected during the final 48 hours of the treatment period and analyzed for bile acid content using an enzymatic assay as described below. Compound efficacy is determined by comparison of the increase in fecal bile acid (FBA) concentration in treated rats to the mean FBA concentration of rats in the vehicle group.

Measurement of Hamster Fecal Bile Acid Concentration (FBA) Total fecal output from individually housed hamsters is collected for 24 or 48 hours, dried under a. stream of nitrogen, pulverized and weighed. Approximately 0.1 gram is weighed out and extracted using an organic solvent (butanol/water). Following separation and drying, the residue is dissolved in methanol and the amount of bile acid present is measured enzymatically using the 3a- hydroxysteroid steroid dehydrogenase reaction with bile acids to reduce NAD. (Mashige et al. Clin. Chem., 27,1352 (1981)).

[3H] Taurocholate Uptake in Rabbit Brush Border Membrane Vesicles (BBMV) Rabbit ileal brush border membranes are prepared from frozen ileal mucosa by the calcium precipitation method describe by Malathi et al. (Biochim. Biophys. Acta, 554, 259 (1979). The method for measuring taurocholate'is similar to that described by Kramer et al. (Biochim.

Biophys. Acta, 1111,93 (1992)) except that the assay volume used is 200 pL instead of 100 uL. Briefly, at room temperature a 190-nul solution containing 2 pm [3H] taurocholate (0.75 HCi), 20 mM tris, 100 mM NaCl, 100 mM mannitol, pH 7.4, is incubated for 5 seconds with 10 L of

brush border membrane vesicles (60-120 pg protein). The incubation is initiated by the addition of the BBMV while vortexing and the reaction is quenched by the addition of 5 mL of ice-cold buffer (20 mM Hepes-tris, 150 mM KC1), followed immediately by filtration through a nylon filter (0.2 pm porosity) and washing with an additional 5 mL of quench buffer.

Dog Model for the Evaluation of Lipid-lowering Drugs (e. g., an ASBT inhibitor or an HMG Co-A reductase inhibitor) Male beagle dogs weighing 6-12 kg, are fed once a day for two hours and given water ad libitum. Dogs are randomly assigned to dosing groups consisting of 6 to 12 dogs each, corresponding to: vehicle, i. g.; 1 mg/kg, i. g.; 2 mg/kg, i. g.; 4 mg/kg, i. g.; 2 mg/kg, p. o. (powder in capsule). Intra-gastric dosing of a therapeutic compound dissolved in aqueous solution (for example, 0.2% Tween 80 solution [polyoxyethylene mono-oleate, Sigma Chemical Co., St. Louis, MO]) is performed using a gavage tube. Prior to initiation of dosing, blood samples are drawn from the cephalic vein before the morning feeding in order to evaluate serum cholesterol (total and HDL) and triglycerides. For several consecutive days animals are dosed in the morning prior to feeding. Animals are thereafter allowed to eat for two hours before remaining food was removed. Feces are collected over a 2-day period at the end of the study and were analyzed for bile acid or lipid content. Blood samples are also collected at the end of the treatment period for comparison with pre-study serum lipid levels. Statistical significance will be determined using the standard Student's T-test, with p<. 05.

Dog Serum Lipid Measurement Blood is collected from the cephalic veins of fasted dogs using serum separator tubes (Vacutainer SST, Becton Dickinson and Co., Franklin Lakes, NJ). The blood is centrifuged at 2000 rpm for 20 minutes and the serum decanted.

Total cholesterol is measured in a 96-well format using a Wako enzymatic diagnostic kit (Cholesterol CII) (Wako Chemicals, Richmond, VA), utilizing the cholesterol oxidase reaction to produce hydrogen peroxide, which is measured colorimetrically. A standard curve from 0.5 to 10 gag cholesterol is prepared in the first two columns of the plate. The serum samples (20-40, uL, depending on the expected lipid concentration) or known serum control samples were added to individual wells in duplicate.

Water is added to bring the volume to 100, ut in each well.

A 100-, ul aliquot of color reagent is added to each well, and the plates are read at 500 nm after a 15-minute incubation at 37° C.

HDL cholesterol is assayed using Sigma kit No. 352-3 (Sigma Chemical Co., St. Louis, MO), which utilizes dextran sulfate and Mg2+ to selectively precipitate LDL and VLDL. A volume of 150, uL of each serum sample is added to individual microfuge tubes, followed by 15, uL of HDL cholesterol reagent (Sigma 352-3). Samples are mixed and centrifuged at 5000 rpm for 5 minutes. A 50, uL aliquot of the supernatant is then mixed with 200, cul of saline and assayed using the same procedure as for total cholesterol measurement.

Triglycerides is measured using Sigma kit No. 337 in a 96-well plate format. This procedure measures the release glycerol from triglycerides with lipoprotein lipase. Standard solutions of glycerol (Sigma 339-11)

ranging from 1 to 24 Hg are used to generate the standard curve. Serum samples (20-40 AL, depending on the expected lipid concentration) are added to wells in duplicate.

Water is added to bring the volume to 100 AL in each well and 100 AL of color reagent is also added to each well.

After mixing and a 15-minute incubation, the plates will be read at 540 nm and the triglyceride values will be calculated from the standard curve. A replicate plate also will be run using a blank enzyme reagent to correct for any endogenous glycerol in the serum samples.

Dog Fecal Bile Acid Measurement Fecal samples are collected to determine the fecal bile acid (FBA) concentration for each animal. Fecal collections are made during the final 48 hours of the study, for two consecutive 24-hour periods between 9: 00 a. m. and 10: 00 a. m. each day, prior to dosing and feeding.

The separate two-day collections from each animal are weighed, combined and homogenized with distilled water in a processor (Cuisinart) to generate a homogeneous slurry.

A sample of 1. 4 g of the homogenate is extracted in a final concentration of 50% tertiary butanol/distilled water (2: 0.6) for 45 minutes in a 37° water bath and centrifuged for 13 minutes at 2000 x G. The concentration of bile acids (mmoles/day) is determined using a 96-well enzymatic assay system. A 20-//L aliquot of the fecal extract is added to two sets each of triplicate wells in a 96-well assay plate. A standardized sodium taurocholate solution and a standardized fecal extract solution (previously made from pooled samples and characterized for its bile acid concentration) are also analyzed for assay quality control. Aliquots of sodium taurocholate (20 AL), serially diluted to generate a standard curve, are similarly added to two sets of triplicate wells. A 230-AL

reaction mixture containing 1M hydrazine hydrate, 0.1 M pyrophosphate and 0.46 mg/ml NAD is added to each well. A 50-pL aliquot of 3a-hydroxysteroid dehydrogenase enzyme (HSD; 0.8 units/ml) or assay buffer (0.1 M sodium pyrophosphate) is then added to one of the two sets of triplicates. All reagents are obtained from Sigma Chemical Co., St. Louis, MO. Following 60 minutes of incubation at room temperature, the optical density at 340 nm is measured and the mean of each set of triplicate samples was calculated. The difference in optical density HSD enzyme is used to determine the bile acid concentration (mM) of each sample, based on the sodium taurocholate standard curve. The bile acid concentration of the extract, the weight of the fecal homogenate (grams) and the body weight of the animal is used to calculate the corresponding FBA concentration in mmoles/kg/day for each animal. The mean FBA concentration (mmoles/kg/day) of the vehicle group is subtracted from the FBA concentration of each treatment group to determine the increase (delta value) in FBA concentration as a result of the treatment.

Hamster Intestinal Cholesterol Absorption Assay Various compounds can be shown to inhibit cholesterol absorption from the intestinal tract. These compounds lower serum cholesterol levels by reducing intestinal absorption of cholesterol from both exogenous sources (dietary cholesterol) and endogenous cholesterol (secreted by the gall bladder into the intestinal tract).

In hamsters the use of a dual-isotope plasma ratio method to measure intestinal cholesterol absorption will be refined and evaluated as described by Turley et al. (J.

Lipid Res., 35, 329-339 (1994)).

'Male hamsters weighing 80-100 g are given food and water ad libitum in a room with 12-hour alternating

periods of light and dark. Four hours into the light period, each hamster is administered an intravenous dose of 2.5 pCi of [1, 2-3H] cholesterol suspended in Intralipid (20%), followed by an oral dose of [4-l4C] cholesterol in an oil vehicle containing medium-chain triglycerides (MCT).

The i. v. dose is given by injecting a 0.4-mL volume of the Intralipid mixture into the distal femoral vein. The oral dose is given by gavaging a 0.6-mL volume of the MCT oil mixture intragastrically via a polyethylene tube. After 72 hours the hamsters are bled and the amount of [3H] and [14C] in the plasma and in the original radiolabelled dosing mixtures are determined by liquid scintillation spectrometry. The cholesterol absorption is calculated from the following equation: Percent cholesterol absorbed = % of oral dose per mL of 72-hour plasma sample x 100 % of i. v. dose per mL of 72-hour plasma sample Evaluation of Plasma Lipids and Atherosclerotic Lesions in Rabbits Rabbit plasma lipids are assayed using standard methods as reported by Schuh et al., J. Clin. Invest., 91, 1453-1458 (1993). Groups of male New Zealand white rabbits are placed on a standard diet (lOOg/day) supplemented with 0.3% cholesterol and 2% corn oil (Zeigler Bothers, Inc., Gardners, PA). Water is available ad libitum. Groups of control and treated animals are sacrificed after one and three months of treatment. Blood samples are collected for determination of plasma lipid concentrations. Tissues are removed for characterization of atherosclerotic lesions and aorta vascular response.

a. Plasma Lipids Plasma for lipid analysis is obtained by withdrawing blood from the ear vein into EDTA-containing tubes (Vacutainer; Becton Dickenson & Co., Rutherford, NJ), followed by centrifugation of the cells. Total cholesterol is determined enzymatically, using the cholesterol oxidase reaction (C. A. Allain et al., Clin. Chem., 20,470-475 (1974)). HDL cholesterol is also measured enzymatically, after selective precipitation of LDL and VLDL by dextran sulfate with magnesium (Warnick et al., Clin. Chem., 28, 1379-1388 (1982)). Plasma triglyceride levels are determined by measuring the amount of glycerol released by lipoprotein lipase through an enzyme-linked assay (G.

Bucolo et al., Clin. Chem., 19, 476-482 (1973)).. b. Atherosclerotic Lesions Animals are sacrificed by pentobarbital injection.

Thoracic aortas are rapidly removed and fixed by immersion in 10% neutral buffered formalin, and stained with oil red O (0.3%). After a single longitudinal incision along the wall opposite the arterial ostia, the vessels are pinned open for evaluation of the plaque area. The percent plaque coverage is determined from the values for the total area examined and the stained area by threshold analysis using a true color image analyzer (Videometric 150; American Innovision, Inc., San Diego, CA) interfaced to a color camera (Toshiba 3CCD) mounted on a dissecting microscope. Tissue cholesterol is measured enzymatically as previously described, after extraction with a chloroform/methanol mixture (2: 1, according to the method of Folch et al. (J. Biol. Chem., 226,497-509 (1957)). c. Aorta Vascular Response The abdominal aortas are rapidly excised after injection of sodium pentobarbital and placed in oxygenated Krebs- bicarbonate buffer. After removal of perivascular tissue,

3-mm ring segments are cut, placed in a 37° C muscle bath containing Krebs-bicarbonate solution, and suspended between two stainless steel wires, one of which is attached to a force transducer (Grass Instrument Co., Quincy, MA). Force changes in response to angiotensin II added to the bath will be recorded on a chart recorder.

Evaluation of plasma Lipids and Atherosclerotic Lesions in Mouse Models of Atherosclerosis Male LDL receptor (-/-) mice (6-8 weeks of age) are obtained from the Jackson Laboratories (Bar Harbor, ME) and are permitted an acclimatization period of one week on normal diet. Mice are then placed on a diet enriched in saturated fat (21% wt/wt) and cholesterol (0.15% wt/wt; Harlan Teklad, catalog # 88137). Pelleted diets are prepared by Research Diets, New Brunswick, NJ. Compounds are administered by mixing the drug in the diet at the indicated concentrations. On occasion, drugs can be administered in the drinking water. Mice are maintained on the above regimens for a minimum of 8 weeks and usually a total of 12 weeks.

Male ApoE (-/-) mice are obtained from the Jackson Laboratories (Bar Harbor, ME) and are permitted an acclimatization period of one week on normal diet. Mice (6 weeks of age) are then placed on a normal chow diet (Purina Certified 5002 Diet) or on a saturated fat (21% wt/wt) and cholesterol (0.15% wt/wt; Harlan Teklad, catalog # 88137) to accelerate the rate of atherosclerosis formation. Pelleted diets are prepared by Research Diets, New Brunswick, NJ. Compounds are administered by mixing the drug in the diet at the indicated concentrations.

Mice are maintained on the above regimens for a minimum of 8 weeks and usually a total of 12 weeks.

a. Lipid Analyses Serum cholesterol concentrations were determined by enzymatic assay and lipoprotein-cholesterol distribution was determined by size exclusion chromatography as described previously (Daugherty A and Rateri D, Coronary Artery Dis. 2 : 775-787 (1991). b. Quantification and histological analyses of the atherosclerotic lesions The extent of the aortic intima covered by grossly discernable atherosclerotic lesions can be quantified by en face analysis of the aorta (from the top of the heart to the iliac bifurcation) as described previously (Daugherty A et al. J. Clin. Invest. 100: 1575-1580 (1997); Daugherty A at al. J. Clin. Invest. 105: 1605-1612 (2000).

Alternatively, atherosclerotici lesion area can be determined in the aortic roots of animals which correlates extremely well with en face atherosclerotic lesion area assessment, but allows histologc evaluation of the quality of the lesions themselves. Mice are euthanized with C02 gas and blood is removed by retroorbital collection.

Hearts are immediately removed and fixed in phosphate buffered formalin. After 24 hours, the bottom two-thirds of the hearts are removed by carefully sectioning the heart just below the atria. The remaining top portions of the hearts are embedded in paraffin and 4 im sections are cut. Every 6th section is evaluated for cross sectional area of atherosclerotic lesions by hematoxylin and eosin staining, beginning where the atrial valves appeared distinctly to where the valves disappear, as described earlier by Nishina et al. (Nishina PM et al, Lipids 28: 599-605 (1993).

Serial sections of the proximal aorta, within 50 microns of the valves and containing remnants of the valve leaflets are selected for immunolocalization of lymphocytes, (anti-CD3), macrophages (anti-CD1) and smooth muscle cells (SMA) and counterstained using hemotoxylin or methyl green. All lesions contained within one aortic section per individual are evaluated. Lesions are characterized as early (Stary classification I and II) or complex (Stary classification III and IV).

T cell quantification in atherosclerotic lesions is performed on sections stained with an anti-CD3 antibody followed by digital image analysis on a computer controlled Olympus AX-70 Provis microscope equipped with a Photometrix digital camera, liquid crystal tunable filter and Isee Imaging software (Inovison Corp, Raleigh, NC).

Procedures for image acquisition and image analysis has been previously described (Ornberg RL. J. Histochem.

Cytochem. 49: 1059-1060 (2000); Ornberg RL et al. Journal of Histochemistry and Cytochemistry. 47 (9): 1-7 (1999).

For smooth muscle cell content, aortic root section images were captured using a Zeiss Axiophot equipped with a Spot XX camera and a 10X objective with a 1.6X magnification ring. Lesion area positively stained for SMA was measured by selecting threshold criteria to detect 1% of a negative control tissue (lymph node) and >85% of a positive control, which was typically a normal media. All lesions are included in the analysis; early or complex lesion assignment is noted during data capture. All measurements are performed by blinded observers and analyzed with measured Area of smooth muscle actin by quantitative image analysis Optimus 6.1.3.

c. Statistical Analyses Statistically significant differences among the means of different groups are tested using one-way analysis of variance (NOVA). j. Examples of Embodiments The following non-limiting examples serve to illustrate various aspects of the present invention.

Example 1. Pharmaceutical Compositions 100 mg tablets of the composition set forth in Table X-1 can be prepared using wet granulation techniques: Table X-1 Ingredient Weight (mg) Compound A-7 (Benzothiepine) 5 Compound B-18 (Celecoxib) 20 Lactose 54 Microcrystalline Cellulose 15 Hydroxypropyl Methylcellulose 3 Croscarmelose Sodium 2 Magnesium Stearate 1 Total Tablet Weight 100 Example 2. Pharmaceutical Compositions 100 mg tablets of the composition set forth in Table X-2 can be prepared using direct compression techniques: Table X-2 Ingredient Weight (mg) Compound A-7 (Benzothiepine) 5 Compound B-18 (Celecoxib) 20 Microcrystalline Cellulose 69. 5 Colloidal Silicon Dioxide 0. 5 Talc 2.5 Croscarmelose Sodium 2 Magnesium Stearate 0. 5 Total Tablet Weight 100

Combinations Tables X-3 and X-3A illustrate, by way of example and not limitation, some of the many combinations of the present invention wherein the combination comprises an amount of an ASBT inhibitor (Component 1) and an amount of a cyclooxygenase-2 selective inhibitor (Component 2), wherein the amount of the ASBT inhibitor and the amount of the cyclooxygenase-2 selective inhibitor together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the ASBT inhibitor and the cyclooxygenase-2 selective inhibitor.

Table X-3 Example Number Component 1 Component 2 IxA3B-18 2x A-3 B-19 3x A-3 B-20 4x A-3 B-21 5x A-3 B-22 6x A-3 B-23 7x A-3 B-24 8x A-5 B-18 9x A-5 B-19 10x A-5 B-20 llx A-5 B-21 12x A-5 B-22 13x A-5 B-23 14x A-5 B-24 15x A-7 B-18 16x A-7 B-19 17x A-7 B-20 18x A-7 B-21 l9x A-7 B-22 20x A-7 B-23 Example Number Component 1 Component 2 21x A-7 B-24 Table X-3A Example Number Component 1 Component 2 22X A-3 D-1 23X A-3 D-2 24X A-3 D-3 25X A-3 D-4 26X A-3 D-5 27X A-3 D-6 28X A-3 D-7 29X A-3 D-8 30X A-3 D-9 31X A-3 D-10 32X A-3 D-11 33X A-3 D-12 34X A-3 D-13 35X A-3 D-14 36X A-3 D-15 37X A-3 D-16 38X A-3 D-17 39X A-3 D-18 40X A-3 D-19 41X A-3 D-20 42X A-3 D-21 43X A-3 D-22 44X A-3 D-23 45X A-3 D-24 46X A-3 D-25 47X A-3 D-26 48X A-3 D-27 49X A-3 D-28 50X A-3 D-29 51X A-3 D-30 52X A-3 D-31 53X A-3 D-32 54X A-3 D-33 55X A-3 D-34 56X A-3 D-35 57X A-3 D-36 58X A-3 D-37 59X A-3 D-38 60X A-3 D-39 61X A-3 D-40 62X A-3 D-41 63X A-3 D-42 64X A-3 D-43 65X A-3 D-44 66X A-3 D-45 67X A-3 D-46 Example Number Component 1 Component 2 68X A-3 D-47 69X A-3 D-48 70X A-3 D-49 71X A-3 D-50 72X A-3 D-51 73X A-3 D-52 74X A-3 D-53 75X A-3 D-54 76X A-3 D-55 77X A-3 D-56 78X A-3 D-57 79X A-3 D-58 80X A-3 D-59 81X A-3 D-60 82X A-3 D-61 83X A-3 D-62 84X A-3 D-63 85X A-3 D-64 86X A-3 D-65 87X A-3 D-66 88X A-3 D-67 89X A-3 D-68 90X A-3 D-69 91X A-3 D-70 92X A-3 D-71 93X A-3 D-72 94X A-3 D-73 95X A-3 D-74 96X A-3 D-75 97X A-3 D-76 98X A-3 D-77 99X A-3 D-78 100X A-3 D-79 101X A-3 D-80 102X 1-3 D-81 103X A-3 D-82 104X A-3 D-83 105X A-3 D-84 106X A-3 D-85 107X A-3 D-86 108X A-3 D-87 109X A-3 D-88 110X A-3 D-89 111X A-3 D-90 112X A-3 D-91 113X A-3 D-92 114X A-3 D-93 115X A-3 D-94 Example Number Component 1 Component 2 116X A-3 D-95 117X A-3 D-96 118X A-3 D-97 119X A-3 D-98 120X A-3 D-99 121X A-3 D-100 122X A-3 D-101 123X A-3 D-102 124X A-3 D-103 125X A-3 D-104 126X A-3 D-105 127X A-3 D-106 128X A-3 D-107 129X A-3 D-108 130X A-3 D-109 131X A-3 D-110 132X A-3 D-111 133X A-3 D-112 134X A-3 D-113 135X A-3 D-114 136X A-3 D-115 137X A-3 D-116 138X A-3 D-117 139X A-3 D-118 140X A-3 D-119 141X A-3 D-120 142X A-3 D-121 143X A-3 D-122 144X A-3 D-123 145X A-3 D-124 146X A-3 D-125 147X A-3 D-126 148X A-3 D-127 149X A-3 D-128 150X A-3 D-129 151X A-3 D-130 152X A-3 D-131 153X A-3 D-132 154X A-3 D-133 155X A-3 D-134 156X A-3 D-135 157X A-3 D-136 158X A-3 D-137 159X A-3 D-138 160X A-3 D-139 161X A-3 D-140 162X A-3 D-141 163X A-3 D-142 Example Number Component 1 Component 2 164X A-3 D-143 165X A-3 D-144 166X A-3 D-145 167X A-3 D-146 168X A-3 D-147 169X A-3 D-148 170X A-3 D-149 171X A-3 D-150 172X A-3 D-151 173X A-3 D-152 174X A-3 D-153 175X A-3 D-154 176X A-3 D-155 177X A-3 D-156 178X A-3 D-157 179X A-3 D-158 180X A-3 D-159 181X A-3 D-160 182X A-3 D-161 183X A-3 D-162 184X A-3 D-163 185X A-3 D-164 186X A-3 D 165 187X A-3 D-166 188X A-3 D-167 189X A-3 D-168 190X A-3 D-169 191X A-3 D-170 192X A-3 D-171 193X A-3 D-172 194X A-3 D-173 195X A-3 D-174 196X A-3 D-175 197X A-3 D-176 198X A-3 D-177 199X A-3 D-178 200X A-3 D-179 201X A-3 D-180 202X A-3 D-181 203X A-3 D-182 204X A-3 D-183 205X A-3 D-184 206X A-3 D-185 207X A-3 D-186 208X A-3 D-187 209X A-3 D-188 210X A-3 D-189 211X A-3 D-190 Example Number Component 1 Component 2 212X A-3 D-191 213X A-3 D-192 214X A-3 D-193 215X A-3 D-194 216X A-3 D-195 217X A-3 D-196 218X A-3 D-197 219X A-3 D-198 220X A-3 D-199 221X A-3 D-200 222X A-3 D-201 223X A-3 D-202 224X A-3 D-203 225X A-3 D-204 226X A-3 D-205 227X A-3 D-206 228X A-3 D-207 229X A-3 D-208 230X A-3 D-209 231X A-3 D-210 232X A-3 D-211 233X A-3 D-212 234X A-3 D-213 235X A-3 D-214 236X A-3 D-215 237X A-3 D-216 238X A-3 D-217 239X A-3 D-218 240X A-3 D-219 241X A-3 D-220 242X A-3 D-221 243X A-3 D-222 244X A-3 D-223 245X A-3 D-224 246X A-3 D-225 247X A-3 D-226 248X A-3 D-227 249X A-3 D-228 250X A-3 D-229 251X A-3 D-230 252X A-3 D-231 253X A-3 D-232 254X A-5 D-1 255X A-5 D-2 256X A-5 D-3 257X A-5 D-4 258X A-5 D-5 259X A-5 D-6 Example Number Component 1 Component 2 260X 261X A-5 D-8 262X A-5 D-9 263X A-5 D-10 264X A-5 D-11 265X A-5 D-12 266X A-5 D-13 267X A-5 D-14 268X A-5 D-15 269X A-5 D-16 270X A-5 D-17 271X A-5 D-18 272X A-5 D-19 273X A-5 D-20 274X A-5 D-21 275X A-5 D-22 276X A-5 D-23 277X A-5 D-24 278X A-5 D-25 279X A-5 D-26 280X A-5 D-27 281X A-5 D-28 282X A-5 D-29 283X A-5 D-30 284X A-5 D-31 285X A-5 D-32 286X A-5 D-33 287X A-5 D-34 288X A-5 D-35 289X A-5 D-36 290X A-5 D-37 291X A-5 D-38 292X A-5 D-39 293X A-5 D-40 294X A-5 D-41 295X A-5 D-42 296X A-5 D-43 297X A-5 D-44 298X A-5 D-45 299X A-5 D-46 300X A-5 D-47 301X A-5 D-48 302X A-5 D-49 303X A-5 D-50 304X A-5 D-51 305X A-5 D-52 306X A-5 D-53 307X A-5 D-54 Example Number Component 1 Component 2 308X A-5 D-55 309X A-5 D-56 310X A-5 D-57 311X A-5 D-58 312X A-5 D-59 313X A-5 D-60 314X A-5 D-61 315X A-5 D-62 316X A-5 D-63 317X A-5 D-64 318X A-5 D-65 319X A-5 D-66 320X A-5 D-67 321X A-5 D-68 322X A-5 D-69 323X A-5 D-70 324X A-5 D-71 325X A-5 D-72 326X A-5 D-73 327X A-5 D-74 328X A-5 D-75 329X A-5 D-76 330X A-5 D-77 331X A-5 332X A-5 D-79 333X A-5 D-80 334X A-5 D-81 335X A-5 D-82 336X A-5 D-83 337X A-5 D-84 338X A-5 D-85 339X A-5 D-86 340X A-5 D-87 341X A-5 D-88 342X A-5 D-89 343X A-5 D-90 344X A-5 D-91 345X A-5 D-92 346X A-5 D-93 347X A-5 348X A-5 D-95 349X A-5 D-96 350X A-5 D-97 351X A-5 D-98 352X A-5 D-99 353X A-5 D-100 354X A-5 D-101 355X A-5 D-102 Example Number Component Component 2 356X A-5 D-103 357X A-5 D-104 358X A-5 D-105 359X A-5 D-106 360X A-5 D-107 361X A-5 D-108 362X A-5 D-109 363X A-5 D-110 364X A-5 D-111 365X A-5 D-112 366X A-5 D-113 367X A-5 D-114 368X A-5 D-115 369X A-5 D-116 370X A-5 D-117 371X A-5 D-118 372X A-5 D-119 373X A-5 D-120 374X A-5 D-121 375X A-5 D-122 376X A-5 D-123 377X A-5 D-124 378X A-5 D-125 379X A-5 D-126 380X A-5 D-127 381X A-5 D-128 382X A-5 D-129 383X A-5 D-130 384X A-5 D-131 385X A-5 D-132 386X A-5 D-133 387X A-5 D-134 388X A-5 D-135 389X A-5 D-136 390X A-5 D-137 391X A-5 D-138 392X A-5 D-139 393X A-5 D-140 394X A-5 D-141 395X A-5 D-142 396X A-5 D-143 397X A-5 D-144 398X A-5 D-145 399X A-5 D-146 400X A-5 D-147 401X A-5 D-148 402X A-5 D-149 403X A-5 D-150 Example Number Component 1 Component 2 404X A-5 D-151 405X A-5 D-152 406X A-5 D-153 407X A-5 D-154 408X A-5 D-155 409X A-5 D-156 410X A-5 D-157 411X A-5 D-158 412X A-5 D-159 413X A-5 D-160 414X A-5 D-161 415X A-5 D-162 416X A-5 D-163 417X A-5 D-164 418X A-5 D-165 419X A-5 D-166 420X A-5 D-167 421X A-5 D-168 422X A-5 D-169 423X A-5 D-170 424X A-5 D-171 425X A-5 D-172 426X A-5 D-173 427X A-5 D-174 428X A-5 D-175 429X A-5 D-176 430X A-5 D-177 431X A-5 D-178 432X A-5 D-179 433X A-5 D-180 434X A-5 D-181 435X A-5 D-182 436X A-5 D-183 437X A-5 D-184 438X A-5 D-185 439X A-5 D-186 440X A-5 D-187 441X A-5 D-188 442X A-5 D-189 443X A-5 D-190 444X A-5 D-191 445X A-5 D-192 446X A-5 D-193 447X A-5 D-194 448X A-5 D-195 449X A-5 D-196 450X A-5 D-197 451X A-5 D-198 Example Number Component 1 Component 2 452X A-5 D-199 453X A-5 D-200 454X A-5 D-201 455X A-5 D-202 456X A-5 D-203 457X A-5 D-204 458X A-5 D-205 459X A-5 D-206 460X A-5 D-207 461X A-5 D-208 462X A-5 D-209 463X A-5 D-210 464X A-5 D-211 465X A-5 D-212 466X A-5 D-213 467X A-5 D-214 468X A-5 D-215 469X A-5 D-216 470X A-5 D-217 471X A-5 D-218 472X A-5 D-219 473X A-5 D-220 474X A-5 D-221 475X A-5 D-222 476X A-5 D-223 477X A-5 D-224 478X A-5 D-225 479X A-5 D-226 480X A-5 D-227 481X A-5 D-228 482X A-5 D-229 483X A-5 D-230 484X A-5 D-231 485X A-5 D-232 486X A-7 D-1 487X A-7 D-2 488X A-7 D-3 489X A-7 D-4 490X A-7 D-5 491X A-7 D-6 492X A-7 D-7 493X A-7 D-8 494X A-7 D-9 495X A-7 D-10 496X A-7 D-11 497X A-7 D-12 498X A-7 D-13 499X A-7 D-14 Example Number Component 1 Component 2 500X A-7 D-15 501X A-7 D-16 502X A-7 D-17 503X A-7 D-18 504X A-7 D-19 505X A-7 D-20 506X A-7 D-21 507X A-7 D-22 508X A-7 D-23 509X A-7 D-24 510X A-7 D-25 511X A-7 D-26 512X A-7 D-27 513X A-7 D-28 514X A-7 D-29 515X A-7 D-30 516X A-7 D-31 517X A-7 D-32 518X A-7 D-33 519X A-7 D-34 520X A-7 D-35 521X A-7 * D-36 522X A-7 D-37 523X A-7 D-38 524X A-7 D-39 525X A-7 D-40 526X A-7 D-41 527X A-7 D-42 528X A-7 D-43 529X A-7 D-44 530X A-7 D-45 531X A-7 D-46 532X A-7 D-47 533X A-7 D-48 534X A-7 D-49 535X A-7 D-50 536X A-7 D-51 537X A-7 D-52 538X A-7 D-53 539X A-7 D-54 540X A-7 D-55 541X A-7 D-56 542XA-7D-57 543X A-7 D-58 544X A-7 D-59 545X A-7 D-60 546X A-7 D-61 547X A-7 D-62 Example Number Component 1 Component 2 548X A-7 D-63 549X A-7 D-64 550X A-7 D-65 551X A-7 D-66 552X A-7 D-67 553X A-7 D-68 554X A-7 D-69 555X A-7 D-70 556X A-7 D-71 557X A-7 D-72 558X A-7 D-73 559X A-7 D-74 560X A-7 D-75 561X A-7 D-76 562X A-7 D-77 563X A-7 D-78 564X A-7 D-79 565X A-7 D-80 566X A-7 D-81 567X A-7 D-82 568X A-7 D-83 569X A-7 D-84 570X A-7 D-85 571X A-7 D-86 572X A-7 D-87 573X A-7 D-88 574X A-7 D-89 575X A-7 D-90 576X A-7 D-91 577X A-7 D-92 578X A-7 D-93 579X A-7 D-94 580X A-7 D-95 581X A-7 D-96 582X A-7 D-97 583X A-7 D-98 584X A-7 D-99 585X A-7 D-100 586X A-7 D-101 587X A-7 D-102 588X A-7 D-103 589X A-7 D-104 590X A-7 D-105 591X A-7 D-106 592X A-7 D-107 593X A-7 D-108 594X A-7 D-109 595X A-7 D-110 Example Number Component 1 Component 2 596X A-7 D-111 597X A-7 D-112 598X A-7 D-113 599X A-7 D-114 600X A-7 D-115 601X A-7 D-116 602X A-7 D-117 603X A-7 D-118 604X A-7 D-119 605X A-7 D-120 606X A-7 D-121 607X A-7 D-122 608X A-7 D-123 609X A-7 D-124 610X A-7 D-125 611X A-7 D-126 612X A-7 D-127 613X A-7 D-128 614X A-7 D-129 615X A-7 D-130 616X A-7 D-131 617X A-7 D-132 618X A-7 D-133 619X A-7 D-134 620X A-7 D-135 621X A-7 D-136 622X A-7 D-137 623X A-7 D-138 624X A-7 D-139 625X A-7 D-140 626X A-7 D-141 627X A-7 D-142 628X A-7 D-143 629X A-7 D-144 630X A-7 D-145 631X A-7 D-146 632X A-7 D-147 633X A-7 D-148 634X A-7 D-149 635X A-7 D-150 636X A-7 D-151 637X A-7 D-152 638X A-7 D-153 639X A-7 D-154 640X A-7 D-155 641X A-7 D-156 642X A-7 D-157 643X A-7 D-158 Example Number Component 1 Component 2 644X A-7 D-159 645X A-7 D-160 646X A-7 D-161 647X A-7 D-162 648X A-7 D-163 649X A-7 D-164 650X A-7 D-165 651X A-7 D-166 652X A-7 D-167 653X A-7 D-168 654X A-7 D-169 655X A-7 D-170 656X A-7 D-171 657X A-7 D-172 658X A-7 D-173 659X A-7 D-174 660X A-7 D-175 661X A-7 D-176 662X A-7 D-177 663X A-7 D-178 664X A-7 D-179 665X A-7 D-180 666X A-7 D-181 667X A-7 D-182 668X A-7 D-183 669X A-7 D-184 670X A-7 D-185 671X A-7 D-186 672X A-7 D-187 673X A-7 D-188 674X A-7 D-189 675X A-7 D-190 676X A-7 D-191 677X A-7 D-192 678X A-7 D-193 679X A-7 D-194 680X A-7 D-195 681X A-7 D-196 682X A-7 D-197 683X A-7 D-198 684X A-7 D-199 685X A-7 D-200 686X A-7 D-201 687X A-7 D-202 688X A-7 D-203 689X A-7 D-204 690X A-7 D-205 691X A-7 D-206 Example Number Component 1 Component 2 692X A-7 D-207 693X A-7 D-208 694X A-7 D-209 695X A-7 D-210 696X A-7 D-211 697X A-7 D-212 698X A-7 D-213 699X A-7 D-214 700X A-7 D-215 701X A-7 D-216 702X A-7 D-217 703X A-7 D-218 704X A-7 D-219 705X A-7 D-220 706X A-7 D-221 707X A-7 D-222 708X A-7 D-223 709X A-7 D-224 701X A-7 D-225 711X A-7 D-226 712X A-7 D-227 713X A-7 D-228 714X A-7 D-229 715X A-7 D-230 716X A-7 D-231 717X A-7 D-232

Tables X-4, X-4A and X-4B illustrate, by way of example and not limitation, some further combinations of the present invention wherein the combination comprises an amount of an ASBT inhibitor (Component 1), an amount of a cyclooxygenase-2 selective inhibitor (Component 2) and an amount of an HMG-CoA inhibitor (Component 3), wherein the amount of the ASBT inhibitor, the amount of the cyclooxygenase-2 selective inhibitor and the amount of the HMG-CoA inhibitor together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the ASBT inhibitor and the cyclooxygenase-2 selective inhibitor'and the HMG-CoA inhibitor.

Table X-4 Example Component Compoent Component Number 1 2 3 ly A-3 B-18 C-1 2y A-3 B-19 C-1 3y A-3 B-20 C-1 4y A-3 B-21 C-1 5y A-3 B-22 C-1 6y A-3 B-23 C-1 7y A-3 B-24 C-1 8y A-5 B-18 C-1 9y A-5 B-19 C-1 10y A-5 B-20 C-1 lly A-5 B-21 C-1 12y A-5 B-22 C-1 13y A-5 B-23 C-1 14y A-5 B-24 C-1 15y A-7 B-18 C-1 16y A-7 B-19 C-1 17y A-7 B-20 C-1 18y A-7 B-21 C-1 l9y A-7 B-22 C-1 Example Component Component Component Number 1 2 3 20y A-7 B-23 C-1 21y A-7 B-24 C-1 22y A-3 B-18 C-2 23y A-3 B-19 C-2 24y A-3 B-20 C-2 25y A-3 B-21 C-2 26y A-3 B-22 C-2 27y A-3 B-23 C-2 28y A-3 B-24 C-2 29y A-5 B-18 C-2 30y A-5 B-19 C-2 31y A-5 B-20 C-2 32y A-S B-21 C-2 33y A-5 B-22 C-2 34y A-5 B-23 C-2 35y A-5 B-24 C-2 36y A-7 B-18 C-2 37y A-7 B-19 C-2 38y A-7 B-20 C-2 39y A-7 B-21 C-2 40y A-7 B-22 C-2 41y A-7 B-23 C-2 42y A-7 B-24 C-2 43y A-3 B-18 C-3 44y A-3 B-19 C-3 45y A-3 B-20 C-3 46y A-3 B-21 C-3 47y A-3 B-22 C-3 48y A-3 B-23 C-3 49y A-3 B-24 C-3 50y A-5 B-18 C-3 51y A-5 B-19 C-3 52y A-5 B-20 C-3 S3y A-5 B-21 C-3 54y A-5 B-22 C-3 55y A-5 B-23 C-3 Example Component Component Component Number 1 2 3 56y A-5 B-24 C-3 57y A-7 B-18 C-3 58y A-7 B-19 C-3 59y A-7 B-20 C-3 60y A-7 B-21 C-3 61y A-7 B-22 C-3 62y A-7 B-23 C-3 63y A-7 B-24 C-3 64y A-3 B-18 C-4 65y A-3 B-19 C-4 66y A-3 B-20 C-4 67y A-3 B-21 C-4 68y A-3 B-22 C-4 69y A-3 B-23 C-4 70y A-3 B-24 C-4 71y A-5 B-18 C-4 72y A-5 B-19 C-4 73y A-5 B-20 C-4 74y A-S B-21 C-4 75y A-5 B-22 C-4 76y A-5 B-23 C-4 77y A-5 B-24 C-4 78y A-7 B-18 C-4 79y A-7 B-19 C-4 80y A-7 B-20 C-4 81y A-7 B-21 C-4 82y A-7 B-22 C-4 83y A-7 B-23 C-4 84y A-7 B-24 C-4 85y A-3 B-18 C-5 86y A-3 B-19 C-5 87y A-3 B-20 C-5 88y A-3 B-21 C-5 89y A-3 B-22 C-5 90y A-3 B-23 C-5 91y A-3 b-24 c-5 Example Component Component Component Number 2 3 92y A-5 B-18 C-5 93y A-5 B-19 C-5 94y A-5 B-20 C-5 95y A-5 B-21 C-5 96y A-5 B-22 C-5 97y A-5 B-23 C-5 98y A-5 B-24 C-5 99y A-7 B-18 C-5 100y A-7 B-19 C-5 101y A-7 B-20 C-5 102y A-7 B-21 C-5 103y A-7 B-22 C-5 104y A-7 B-23 C-5 105y A-7 B-24 C-5 106y A-3 B-18 C-6 107y A-3 B-19 C-6 108y A-3 B-20 C-6 109y A-3 B-21 C-6 110y A-3 B-22 C-6 111y A-3 B-23 C-6 112y A-3 B-24 C-6 113y A-5 B-18 C-6 114y A-5 B-19 C-6 115y A-5 B-20 C-6 116y A-5 B-21 C-6 117y A-5 B-22 C-6 118y A-5 B-23 C-6 119y A-5 B-24 C-6 120y A-7 B-18 C-6 121y A-7 B-19 C-6 122y A-7 B-20 C-6 123y A-7 B-21 C-6 124y A-7 B-22 C-6 125y A-7 B-23 C-6 126y A-7 B-24 C-6 127y A-3 B-18 C-7 Example Component Component Component Number 1 2 3 128y A-3 B-19 C-7 129y A-3 B-20 C-7 130y A-3 B-21 C-7 131y A-3 B-22 C-7 132y A-3 B-23 C-7 133y A-3 B-24 C-7 134y A-5 B-18 C-7 135y A-5 B-19 C-7 136y A-5 B-20 C-7 137y A-5 B-21 C-7 138y A-5 B-22 C-7 139y A-5 B-23 C-7 140y A-5 B-24 C-7 141y A-7 B-18 C-7 142y A-7 B-19 C-7 143y A-7 B-20 C-7 144y A-7 B-21 C-7 145y A-7 B-22 C-7 146y A-7 B-23 C-7 147y A-7 B-24 C-7 148y A-3 B-18 C-8 149y A-3 B-19 C-8 150y A-3 B-20 C-8 151y A-3 B-21 C-8 152y A-3 B-22 C-8 153y A-3 B-23 C-8 154y A-3 B-24 C-8 155y A-5 B-18 C-8 156y A-5 B-19C-8 157y A-5 B-20 C-8 158y A-5 B-21 C-8 159y A-5 B-22 C-8 160y A-5 B-23 C-8 161y A-5 B-24 C-8 162y A-7 B-18 C-8 163y A-7 B-19 C-8 Example Component Component Component Number 1 2 3 164y A-7 B-20 C-8 165y A-7 B-21 C-8 166y A-7 B-22 C-8 167y A-7 B-23 C-8 A-7 B-24 C-8 169y A-3 B-18 C-9 170y A-3 B-19 C-9 171y A-3 B-20C-9 172y A-3 B-21 C-9 173y A-3 B-22 C-9 174y A-3 B-23 C-9 175y A-3 B-24 C-9 176y A-5 B-18 C-9 177y A-5 B-19 C-9 178y A-5 B-20 C-9 179y A-5 B-21 C-9 180y A-5 B-22 C-9 181y A-5 B-23 C-9 182y A-5 B-24 C-9 183y A-7 B-18 C-9 184y A-7 B-19 C-9 185y A-7 B-20 C-9 186y A-7 B-21 C-9 187y A-7 B-22 C-9 188y A-7 B-23 C-9 189y A-7 B-24 C-09 Table X-4A Example Component 2 Component 3 Component 1 Number 190y Any one or more of D-1 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21, A-22 Table 8 191y Any one or more of D-2 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 192y Any one or more of D-3 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 193y Any one or more of D-4 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 194y Any one or more of D-5 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 195y Any one or mor eof D-6 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 196y Any one or more of D-7 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 197y Any one or more of D-8 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 198y Any one or more of D-9 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 199y Any one or more of D-10 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 200y Any one or more of D-11 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 201y Any one or more of D-12 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 202y Any one or more of D-13 Any one or more A-1, A-2, A-3, A-of C-l, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 203y Any one or more of D-14 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 204y Any one or more of D-15 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 205y Any one or more of D-16 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 206y Any one or more of D-17 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 207y Any one or more of D-18 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 208y Any one or more of D-19 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 209y Any one or more of D-20 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 210y Any one or more of D-21 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 211y Any one or more of D-22 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 212y Any one or more of D-23 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 213y Any one or more of D-24 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 . 214y Any one or more of D-25 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 215y Any one or more of D-26 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 216y Any one or more of D-27 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 217y Any one or more of D-28 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 218y Any one or more of D-29 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 219y Any one or more of D-30 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 220y Any one or more of D-31 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 221y Any one or more of D-32 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 222y Any one or more of D-33 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 223y Any one or more of D-34 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 224y Any one or more of D-35 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4,'C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 225y Any one or more of D-36 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 226y Any one or more of D-37 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 227y Any one or more of D-38 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 228y Any one or more of D-39 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 229y Any one or more of D-40 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 230y Any one or more of D-41. Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 231y Any one or more of D-42 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 232y Any one or more of D-43 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 233y Any one or more of D-44 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 234y Any one or more of D-45 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 235y Any one or more of D-46 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 236y Any one or more of D-47 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Example 237y Any one or more of D-48 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 238y Any one or more of D-49 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 239y Any one or more of D-50 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 240y Any one or more of D-51 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 241y Any one or more of D-52 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 242y Any one or more of D-53 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 243y Any one or more of D-54 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 244y Any one or more of D-55 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 245y Any one or more of D-56 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 246y Any one or more of D-57 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 247y Any one or more of D-58 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 248y Any one or more of D-59 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 249y Any one or more of D-60 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 250y Any one or more of D-61 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 251y Any one or more of D-62 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 252y Any one or more of D-63 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 253y Any one or more of D-64 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 254y Any one or more of D-65 Any one or more A-1, A-2, A-3, A-of C-l, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22. Table 8 Example Component 2 Component 3 Component 1 Number 255y Any one or more of D-66 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 256y Any one or more of D-67 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 257y Any one or more of D-68 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 258y Any one or more of D-69 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 259y Any one or more of D-70 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 260y Any one or more of D-71 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 261y Any one or more of D-72 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 262y Any one or more of D-73 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 263y Any one or more of D-74 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 264y Any one or more of D-75 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 265y Any one or more of D-76 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 266y Any one or more of D-77 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 267y Any one or more of D-78 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7, 3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 268y Any one or more of D-79 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7, 3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 269y Any one or more of D-80 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7, 3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 270y Any one or more of D-81 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 271y Any one or more of D-82 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 272y Any one or more of D-83 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 273y Any one or more of D-84 Any one or more A-l, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 274y Any one or more of D-85 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 275y Any one or more of D-86 Any one or more A-1, A-2, A-3, A-of C-l, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 276y Any one or more of D-87 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 277y Any one or more of D-88 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 278y Any one or more of D-89 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 279y Any one or more of D-90 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 280y Any one or more of D-91 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 281y Any one or more of D-92 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 282y Any one or more of D-93 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 283y Any one or more of D-94 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 284y Any one or more of D-95 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 285y Any one or more of D-96 Any one or more . A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 286y Any one or more of D-97 Any one or more A-1, A-2, A-3, A-of C-l, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 287y Any one or more of D-98 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 288y Any one or more of D-99 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 289y Any one or more of D-100 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 290y Any one or more of D-101 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 291y Any one or more of D-102 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 292y Any one or more of D-103 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 293y Any one or more of D-104 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-l9, A-Inhibitors of 20, A-21 and A-22 Table 8 294y Any one or more of D-105 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 295y Any one or more of D-106 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 296y Any one or more of D-107 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 297y Any one or more of D-108 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 298y Any one or more of D-109 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 299y Any one or more of D-110 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7, 3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 300y Any one or more of D-111 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 301y Any one or more of D-112 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 302y Any one or more of D-113 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 303y Any one or more of D-114 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 304y Any one or more of D-115 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7, 3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 305y Any one or more of D-116 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 306y Any one or more of D-117 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 307y Any one or more of D-118 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 _ Table 8 308y Any one or more of D-119 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 309y Any one or more of D-120 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 310y Any one or more of D-121 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 311y Any one or more of D-122 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 312y Any one or more of D-123 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 313y Any one or more of D-124 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 314y Any one or more of D-125 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 315y Any one or more of D-126 Any one or more A-1, A-2, A-3, A-of C-l, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 316y Any one or more of D-127 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 317y Any one or more of D-128 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 318y Any one or more of D-129 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 319y Any one or more of D-130 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 320y Any one or more of D-131 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 321y Any one or more of D-132 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 322y Any one or more of D-133 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 323y Any one or more of D-134 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 324y Any one or more of D-135 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 325y Any one or more of D-136 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 326y Any one or more of D-137 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 327y Any one or more of D-138 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 328y Any one or more of D-139 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 329y Any one or more of D-140 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 330y Any one or more of D-141 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 331y Any one or more of D-142 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 332y Any one or more of D-143 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 333y Any one or more of D-144 Any one or more A-1, A-2, A-3, A-of C-l, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 334y Any one or more of D-145 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 335y Any one or more of D-146 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 336y Any one or more of D-147 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 337y Any one or more of D-148 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 338y Any one or more of D-149 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 339y Any one or more of D-150 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 340y Any one or more of D-151 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 341y Any one or more of D-152 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase. 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 342y Any one or more of D-153 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 343y Any one or more of D-154 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 344y Any one or more of D-155 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 345y Any one or more of D-156 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 346y Any one or more of D-157 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 347y Any one or more of D-158 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 348y Any one or more of D-159 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 349y Any one or more of D-160 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 350y Any one or more of D-161 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 351y Any one or more of D-162 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 352y Any one or more of D-163 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 353y Any one or more of D-164 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 354y Any one or more of D-165 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 355y Any one or more of D-166 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 356y Any one or more of D-167 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 357y Any one or more of D-168 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 358y Any one or more of D-169 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 359y Any one or more of D-170 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 360y Any one or more of D-171 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 361y Any one or more of D-172 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 362y Any one or more of D-173 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 363y Any one or more of D-174 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 364y Any one or more of D-175 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 365y Any one or more of D-176 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 366y Any one or more of D-177 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 367y Any one or more of D-178 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 368y Any one or more of D-179 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 369y Any one or more of D-180 Any one or more A-1, A-2, A-3, A-of C-l, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 370y Any one or more of D-181 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 371y Any one or more of D-182 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 372y Any one or more of D-183 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 373y Any one or more of D-184 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 374y Any one or more of D-185 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 2 Component 3 Component 1 Number 375y Anyone or more of D-186 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 376y Any one or more of D-187 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 377y Any one or more of D-188 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 378y Any one or more of D-189 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 379y Any one or more of D-190 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 380y Any one or more of D-191 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 381y Any one or more of D-192 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 382y Any one or more of D-193 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 383y Any one or more of D-194 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7, 3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-l9, A-Inhibitors of 20, A-21 and A-22 Table 8 384y Any one or more of D-195 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 385y Any one or more of D-196 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 386y Any one or more of D-197 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Number Component 1 387y Any one or more of D-198 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 388y Any one or more of D-199 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 389y Any one or more of D-200 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 390y Any one or more of D-201 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 391y Any one or more of D-202 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 392y Any one or more of D-203 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 393y Any one or more of D-204 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 394y Any one or more of D-205 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 395y Any one or more of D-206 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 396y Any one or more of D-207 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 397y Any one or more of D-208 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 398y Any one or more of D-209 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 399y Any one or more of D-210 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 400y Any one or more of D-211 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 401y Any one or more of D-212 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 402y Any one or more of D-213 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 403y Any one or more of D-214 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 404y Any one or more of D-215 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 405y Any one or more of D-216 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 406y Any one or more of D-217 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 407y Any one or more of D-218 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 408y Any one or more of D-219 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 409y Any one or more of D-220 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A'-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 410y Any one or more of D-221 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 411y Any one or more of D-222 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 412y Any one or more of D-223 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 413y Any one or more of D-224 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 414y Any one or more of D-225 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 415y Any one or more of D-226 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 416y Any one or more of D-227 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Example Component 2 Component 3 Component 1 Number 417y Any one or more of D-228 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 418y Any one or more of D-229 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 419y Any one or more of D-230 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 420y Any one or more of D-231 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 421y Any one or more of D-232 Any one or more A-1, A-2, A-3, A-of C-1, C-2, C- 4, A-5, A-6, A-7,3, C-4, C-5, C- A-8, A-9, A-10, A-6, C-7, C-8, C- 11, A-12, A-13, A-9, and HMG-CoA 14, A-15, A-16, A-Reductase 17, A-18, A-19, A-Inhibitors of 20, A-21 and A-22 Table 8 Table X-4B Example Component 2 Component 3 Component 1 Number 4226 D-1 to D-5 Any one or more Any one or more of A-1, A-2, A- 3, A-4, A-5, A-3, C-4, C-5, C- _, 6, C-7, C-8, C- 9, A-10, A-11, A-12, A-13, A- 9, and HMG-CoA 14, A-15, A-16, Reductase A-17, A-18, A- 19, A-20, A-21, Inhibitors of A-22 Table 8 423y Any one or more D-6 to D-10 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 424y Any one or more D-11 to D-15 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 425y Any one or more D-16 to D-20 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 Example Component 1 Component 2 Component 3 Number 426y Any one or more D-21 to D-25 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 427y Any one or more D-26 to D-30 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 428y Any one or more D-31 to D-35 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 429y Any one or more D-36 to D-40 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 Example Component 2 Component 3 Number 430y Any one or more D-41 to D-45 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 431y Any one or more D-46 to D-50 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-ll, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 432y Any one or more D-51 to D-55 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-ll, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 433y Any one or more D-56 to D-60 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-ll, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 Example Component 2 Component 3 Component 1 Number 434y Any one or more D-61 to D-65 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 435y Any one or more D-66 to D-70 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 436y Any one or more D-71 to D-75 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 437y Any one or more D-76 to D-80 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 Example.. Component 2 Component 3 Component 1 Number 438y Any one or more D-81 to D-85 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-ll, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 439y Any one or more D-86 to D-90 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-ll, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 440y Any one or more D-91 to D-95 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-ll, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 441y Any one or more D-96 to D-100 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-ll, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 Example Component 2 Component 3 Number 442y Any one or more D-101 to D-105 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 443y Any one or more D-106 to D-110 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 444y Any one or more D-lll to D-115 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-ll, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 445y Any one or more D-116 to D-120 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-ll, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 Example Component 2 Component 3 Component 1 Number 446y Any one or more D-121 to D-125 Any one or ore of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 447y Any one or more D-126 to D-130 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 448y Any one or more D-131 to D-135 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 449y Any one or more D-136 to D-140 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 Example Component 2 Component 3 Component 1 Number 450y Any one or more D-141 to D-145 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 451y Any one or more D-146 to D-150 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 452y Any one or more D-151 to D-155 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 453y Any one or more D-156 to D-160 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 Example Component 2 Component 3 Component 1 Number 454y Any one or more D-161 to D-165 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-ll, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 455y Any one or more D-166 to D-170 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 456y Any one or more D-171 to D-175 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 457y Any one or more D-176 to D-180 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 Example Component 2 Component 3 Component 1 Number 458y Any one or more D-181 to D-185 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 459y Any one or more D-186 to D-190 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-ll, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 460y Any one or more D-191 to D-195 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-ll, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 461y Any one or more D-196 to D-200 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-ll, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 Example Component 2 Component 3 Component 1 Number 462y Any one or more D-201 to D-205 any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 463y Any one or more D-206 to D-210 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 464y Any one or more D-211 to D-215 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 465y Any one or more D-216 to D-220 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-ll, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 Example Component 2 Component 3 Component 1 Number 466y Any one or more D-221 to D-225 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 467y Any one or more D-226 to D-230 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22 468y Any one or more D-231 to D-232 Any one or more of A-1, A-2, A-of C-1, C-2, C- 3, A-4, A-5, A-3, C-4, C-5, C- 6, A-7, A-8, A-6, C-7, C-8, C- 9, A-10, A-11, 9, and HMG-CoA A-12, A-13, A-Reductase 14, A-15, A-16, Inhibitors of A-17, A-18, A-Table 8 19, A-20, A-21 and A-22

Table X-5 illustrates, by way of example and not limitation, some of the many combinations of the present invention wherein the combination comprises an amount of an HMG Co-A reductase inhibitor (Component 1) and an amount of a chromene cyclooxygenase inhibitor (Component 2), wherein the amount of the HMG Co-A reductase inhibitor and the amount of the chromene cyclooxygenase inhibitor together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the HMG Co-A reductase inhibitor and the chromene cyclooxygenase inhibitor.

Table X-5 Example Component 1 Component 2 Number 1z Benfluorex B-3 2z Benfluorex B-4 3z Benfluorex B-5 4z Benfluorex B-6 5z Benfluorex B-7 6zBenfluorexB-8 7z Benfluorex B-9 8z Benfluorex B-10 9z Benfluorex B-11 10z Benfluorex B-12 11z Benfluorex B-13 12z Benfluorex B-14 13z Benfluorex B-15 14z Benfluorex B-16 15zBenfluorexB-17 16z Fluvastatin B-3 17z Fluvastatin B-4 18z Fluvastatin B-5 19z Fluvastatin B-6 20z Fluvastatin B-7 21z Fluvastatin B-8 22z Fluvastatin B-9 23z Fluvastatin B-10 24z Fluvastatin B-11 25z Fluvastatin B-12 26z Fluvastatin B-13 27z Fluvastatin B-14 28z Fluvastatin B-15 29z Fluvastatin B-16 30z Fluvastatin B-17 31z Lovastatin B-3 32z Lovastatin B-4 33z Lovastatin B-5 34z Lovastatin B-6 35z Lovastatin B-7 36z Lovastatin B-8 37z Lovastatin B-9 38z Lovastatin B-10 39z Lovastatin B-11 40z Lovastatin B-12 41z Lovastatin B-13 42z Lovastatin B-14 43z Lovastatin B-15 44z Lovastatin B-16 45z Lovastatin B-17 46z Pravastatin B-3 47z Pravastatin B-4 48z Pravastatin B-5 49z Pravastatin B-6 50z Pravastatin B-7 51z Pravastatin B-8 52z Pravastatin B-9 53z Pravastatin B-10 54z Pravastatin B-11 55z Pravastatin B-12 56z Pravastatin B-13 57z Pravastatin B-14 58z Pravastatin B-15 59z Pravastatin B-16 60z Pravastatin B-17 61z Simvastatin B-3 62z Simvastatin B-4 63z Simvastatin B-5 64z Simvastatin B-6 65z Simvastatin B-7 66z Simvastatin B-8 67z Simvastatin B-9 68z Simvastatin B-10 69z Simvastatin B-11 70z Simvastatin B-12 71z Simvastatin B-13 72z Simvastatin B-14 73z Simvastatin B-15 74z Simvastatin B-16 75z Simvastatin B-17 76z Atorvastatin B-3 77z Atorvastatin B-4 78z Atorvastatin B-5 79z Atorvastatin B-6 80z Atorvastatin B-7 81z Atorvastatin B-8 82z Atorvastatin B-9 83z Atorvastatin B-10 84z Atorvastatin B-11 85z Atorvastatin B-12 86z Atorvastatin B-13 87z Atorvastatin B-14 88z Atorvastatin B-15 89z Atorvastatin B-16 90z Atorvastatin B-17 91z Cerivastatin B-3 92z Cerivastatin B-4 93z Cerivastatin B-5 94z Cerivastatin B-6 95z Cerivastatin B-7 96z Cerivastatin B-8 97z Cerivastatin B-9 98z Cerivastatin B-10 99z Cerivastatin B-11 100z Cerivastatin B-12 101z Cerivastatin B-13 102z Cerivastatin B-14 103z Cerivastatin B-15 104z Cerivastatin B-16 105z Cerivastatin B-17 106z Vervastatin B-3 107z Vervastatin B-4 108z Vervastatin B-5 109z Vervastatin B-6 llOz Vervastatin B-7 lllz Vervastatin B-8 112z Vervastatin B-9 113z Vervastatin B-10 114z Vervastatin B-11 115z Vervastatin B-12 116z Vervastatin B-13 117z Vervastatin B-14 118z Vervastatin B-15 119z Vervastatin B-16 120z Vervastatin B-17 121z Rosuvastatin B-3 (ZD-4522) 122z Rosuvastatin B-4 (ZD-4522) 123z Rosuvastatin B-5 (ZD-4522) 124z Rosuvastatin B-6 (ZD-4522) 125z Rosuvastatin B-7 (ZD-4522) 126z Rosuvastatin B-8 (ZD-4522) 127z Rosuvastatin B-9 (ZD-4522) 128z Rosuvastatin B-10 (ZD-4522) 129z Rosuvastatin B-11 (ZD-4522) 130z Rosuvastatin B-12 (ZD-4522) 131z Rosuvastatin B-13 (ZD-4522) 132z Rosuvastatin B-14 (ZD-4522) 133z Rosuvastatin B-15 (ZD-4522) 134z Rosuvastatin B-16 (ZD-4522) 135z Rosuvastatin B-17 (ZD-4522) 136z Itavastatin B-3 137z Itavastatin B-4 138z Itavastatin B-5 139z Itavastatin B-6 140z Itavastatin B-7 141z Itavastatin B-8 142z Itavastatin B-9 143z Itavastatin 144z Itavastatin 145z Itavastatin B-12 146z Itavastatin B-13 147z Itavastatin B-14 148z Itavastatin B-15 149z Itavastatin B-16 150z Itavastatin 151z Delvastatin B-3 152z Delvastatin B-4 153z Delvastatin B-5 154z Delvastatin B-6 155z Delvastatin B-7 156z Delvastatin B-8 157z Delvastatin B-9 158z Delvastatin B-10 159z Delvastatin B-11 160z Delvastatin B-12 161z Delvastatin B-13 162z Delvastatin B-14 163z Delvastatin B-15 164z Delvastatin B-16 165z Delvastatin B-17 166z Mevastatin B-3 167z Mevastatin B-4 168z Mevastatin B-5 169z Mevastatin B-6 170z Mevastatin B-7 171z Mevastatin B-8 172z Mevastatin B-9 173z Mevastatin B-10 174z Mevastatin B-11 175z Mevastatin B-12 176z Mevastatin B-13 177z Mevastatin B-14 178z Mevastatin B-15 179z Mevastatin B-16 180z Mevastatin B-17

TableS X-5A and X-5B illustrate, by way of example and not limitation, some of the many combinations of the present invention wherein the combination comprises an amount of an HMG Co-A reductase inhibitor (Component 1) and an amount of a cyclooxygenase-2 selective inhibitor (Component 2), wherein the amount of the HMG Co-A reductase inhibitor and the amount of the cyclooxygenase-2 selective inhibitor together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the HMG Co-A reductase inhibitor and the cyclooxygenase-2 selective inhibitor.

Table 5A Example Number Component 1 Component 2 181z Any one or more of Benfluorex, Fluvastatin, Lovastatin, Pravastatin, Simvastatin, Atavastatin, D-1 Cerivastatin, Vervastatin, Rosuvastatin, Itavastatink Delvastatin, and Mevastatin 182z D-2 183z " D-3 184z D-4 185z " D-5 186z D-6 187z D-7 188z " D-8 189z " D-9 190z " D-10 19lz D-11 192z D-12 193z D-13 194z " D-14 195z " D-15 196z " D-16 197z " D-17 198z " D-18 199z " D-19 200z"D-20 201z " D-21 202z D-22 203z " D-23 204z " D-24 205z D-25 206z " D-26 207z " D-28 208z " D-28 209z " D-29 210z " D-30 211z " D-31 212z D-32 213z D-33 214z " D-34 215z D-35 216z " D-36 Example Number Component 1 Component 2 217z " D-37 218z " D-38 219z " D-39 220z " D-40 221z " D-41 222z " D-42 223z " D-43 224z " D-44 225z " D-45 226z " D-46 227z " D-47 228z " D-48 229z " D-49 230z " D-50 231z " D-51 232z " D-52 233z " D-53 234z " D-54 235z " D-55 236z " D-56 237z " D-57 238z " D-58 239z " D-59 240z " D-60 241z " D-61 242z " D-62 243z " D-63 244z " D-64 245z " D-65 246z " D-66 247z " D-67 248z " D-68 249z " D-69 250z " D-70 251z " D-71 252z " D-72 253z " D-73 254z " D-74 255z " D-75 256z " D-76 257z " D-77 258z " D-78 259z " D-79 260z " D-80 261z " D-81 262z " D-82 263z " D-83 264z " D-84 Example Number Component 1 Component 2 265z " D-85 266z " D-86 267z " D-87 268z " D-88 269z " D-89 270z " D-90 271z " D-91 272z " D-92 273z " D-93 274z " D-94 275z " D-95 276z " D-96 277z " D-97 278z " D-98 279z " D-99 280z " D-100 281z " D-101 282z " D-102 283z " D-103 284z " D-104 285z " D-105 286z " D-106 287z " D-107 288z " D-108 289z " D-109 290z " D-110 291z " D-111 292z " D-112 293z " D-113 294z " D-114 295z " D-115 296z " D-116 297z " D-117 298z " D-118 299z " D-119 300z " D-120 301z " D-121 302z " D-122 303z " D-123 304z " D-124 305z " D-125 306z " D-126 307z " D-127 308z " D-128 309z " D-129 310z " D-130 311z " D-131 312z " D-132 Example Number Component 1 Component 2 313z " D-133 314z"D-134 315z " D-135 316z " D-136 317z D-137 318z " D-138 319z " D-139 320z " D-140 321z " D-141 322z D-142 323z " D-143 324z D-144 325z"'D-145 326z D-146 327z " D-147 328z D-148 329z " D-149 330z " D-150 331z " D-151 332z " D-152 333z " D-153 334z " D-154 335z " D-155 336z " D-156 337z " D-157 338z D-158 339z D-159 340z " D-160 341z " D-161 342z " D-162 343z " D-163 344z " D-164 345z " D-165 346z " D-166 347z " D-167 348z " D-168 349z D-169 350z " D-170 351z " D-171 352z " D-172 353z " D-173 354z " D-174 355z " D-175 356z " D-176 357z " D-177 358z " D-178 359z " D-179 360z D-180 Example Number Component 1 Component 2 361z " D-181 362z " D-182 363z " D-183 364z"D-184 365z " D-185 366z " D-186 367z " D-187 368z " D-188 369z " D-189 370z D-190 371z " D-191 372z " D-192 373z " D-193 374z " D-194 375z " D-195 376z " D-196 377z " D-197 378z " D-198 379z D-199 380z " D-200 381z " D-201 382z " D-202 383z " D-203 384z " D-204 385z " D-205 386z D-206 387z " D-207 388z " D-208 389z"D-209 390z " D-210 391z " D-211 392z " D-212 393z " D-213 394z D-214 395z D-215 396z"D-216 397z D-217 398z " D-218 399z " D-219 400z " D-220 401z D-221 402z " D-222 403z D-223 404z " D-224 405z D-225 406z " D-226 407z D-227 408z D-228 Example Number Component 1 Component 2 409z D-229 410z " D-230 411z D-231 412z " D-232 Table 5B Example Number Component 1 Component 2 413z Any one or more of Benfluorex, Fluvastatin, Lovastatin, Pravastatin, Simvastatin, Atavastatin, D-1 to D-5 Cerivastatin, Vervastatin, Rosuvastatin, Itavastatink Delvastatin, and Mevastatin 414z"D-6 to D-10 415z " D-11 to D-15 416z " D-16 to D-20 417z D-21 to D-25 418z D-26 to D-30 419z"D-31 to D-35 420z"D-36 to D-40 421z"D-41 to D-45 422z"D-46 to D-50 423z"D-51 to D-55 424z"D-56 to D-60 425z " D-61 to D-65 426z"D-66 to D-70 427z"D-71 to D-75 428z"D-76 to D-80 429z"D-81 to D-85 430z " D-86 to D-90 431z " D-91 to D-95 432z D-96 to D-100 433z"D-101 to D-105 434z"D-106 to D-110 435z"D-lll to D-115 436z " D-116 to D-120 437z"D-121 to D-125 438z " D-126 to D-130 439z " D-131 to D-135 440z " D-136 to D-140 441z"D-141 to D-145 442z"D-146 to D-150 Example Number Component 1 Component 2 443z"D-151 to D-155 444z"D-156 to D-160 445z " D-161 to D-165 446z"D-166 to D-170 447z"D-171 to D-175 448z " D-176 to D-180 449z"D-181 to D-185 450z"D-186 to D-190 451z " D-191 to D-195 452z"D-196 to D-200 453z D-2 01 to D-2 05 454z " D-206 to D-210 455z " D-211 to D-215 456z"D-216 to D-220 457z"D-221 to D-225 458z"D-226 to D-230 459z"D-231 to D-232

The above-noted combinations of: (1) ASBT inhibitor and COX-2 selective inhibitor (2) ASBT inhibitor, COX-2 selective inhibitor, and HMG Co-A reductase inhibitor, and (3) COX-2 selective inhibitor and HMG Co-A reductase inhibitor may independently be used to reduce total serum cholesterol in mammals including humans.

The above-noted combinations of: (1) ASBT inhibitor and COX-2 selective inhibitor and (2) ASBT inhibitor, COX- 2 selective inhibitor, and HMG Co-A reductase inhibitor may independently be used to reduce serum thromboxane levels in mammals including humans.

The above-noted combinations of: (1) ASBT inhibitor and COX-2 selective inhibitor (2) ASBT inhibitor, COX-2 selective inhibitor, and HMG Co-A reductase inhibitor, and (3) COX-2 selective inhibitor and HMG Co-A reductase inhibitor may independently be used to reduce serum soluble intercellular cell adhesion molecule levels in mammals including humans.

The above-noted combinations of: (1) ASBT inhibitor and COX-2 selective inhibitor (2) ASBT inhibitor, COX-2 selective inhibitor, and HMG Co-A reductase inhibitor, and (3) COX-2 selective inhibitor and HMG Co-A reductase inhibitor may independently be used to reduce the T-cell content of an atherosclerotic lesion developing in mammals including humans.

The above-noted combinations of: (1) ASBT inhibitor and COX-2 selective inhibitor (2) ASBT inhibitor, COX-2 selective inhibitor, and HMG Co-A reductase inhibitor, and (3) COX-2 selective inhibitor and HMG Co-A reductase inhibitor may independently be used to increase smooth muscle cell content of an atherosclerotic lesion developing in the vasculature of mammals including humans.

The above-noted combinations of: (1) ASBT inhibitor and COX-2 selective inhibitor (2) ASBT inhibitor, COX-2 selective inhibitor, and HMG Co-A reductase inhibitor, and (3) COX-2 selective inhibitor and HMG Co-A reductase inhibitor may independently be used to reduce the aortic root atherosclerotic lesion area in mammals including humans.

The above-noted combinations of: (1) ASBT inhibitor and COX-2 selective inhibitor (2) ASBT inhibitor, COX-2 selective inhibitor, and HMG Co-A reductase inhibitor, and (3) COX-2 selective inhibitor and HMG Co-A reductase inhibitor may independently be used either as a treatment or as a prophylactic use in the treatment or prophylaxis of a hypercholesterolemia-related or an inflammation- related condition in a subject in need of such treatment or prevention.

Various Embodiments of the present invention are presented below for illustration.

EMBODIMENTS Various Embodiments are: 1. A method for treating or preventing a hypercholesterolemia-related or an inflammation-related condition in a subject in need of such treatment or prevention, comprising treating the subject with an amount of an apical sodium co-dependent bile acid transport inhibitor, an amount of a cyclooxygenase-2 selective inhibitor or prodrug, wherein the amount of the apical sodium co-dependent bile acid transport inhibitor, the amount of the cyclooxygenase-2 selective inhibitor together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the apical sodium co-

dependent bile acid transport inhibitor and the cyclooxygenase-2 selective inhibitor.

2. The method of Embodiment 1 wherein the amount of the apical sodium co-dependent bile acid transport inhibitor and the amount of the cyclooxygenase-2 selective inhibitor together constitute a hypercholesterolemia- related condition effective amount of the apical sodium co-dependent bile acid transport inhibitor and the cyclooxygenase inhibitor.

3. The method of Embodiment 1 wherein the amount of the apical sodium co-dependent bile acid transport inhibitor and the amount of the cyclooxygenase-2 selective inhibitor together constitute an inflammation-related condition effective amount of the apical sodium co- dependent bile acid transport inhibitor and the cyclooxygenase-2 selective inhibitor.

4. The method of Embodiment 1 wherein the condition is selected from the group consisting of gout, pancreatitis, cholelithiasis, biliary obstruction, ulcerative colitis, Crohn's disease, coronary artery disease, aneurysm, arteriosclerosis, atherosclerosis, myocardial infarction, embolism, stroke, thrombosis, angina, coronary plaque inflammation, bacterial-induced inflammation, viral induced inflammation, and inflammation wherein the inflammation is associated with a surgical procedure involving an artery, a vein or a capillary.

5. The method of Embodiment 4 wherein the condition is selected from the group consisting of coronary artery disease, atherosclerosis, and thrombosis.

6. The method of Embodiment 5 wherein the condition is coronary artery disease.

7. The method of Embodiment 1 wherein the cyclooxygenase-2 selective inhibitor is D-1, D-2, D-3, D- 4, D-5, D-6, D-7, D-8, D-9, D-10, D-11, D-12, D-13, D-14, D-15, D-16, D-17, celecoxib (D-18), D-19, D-20, rofecoxib (D-21), D-22, D-23, D-24, D-25, D-26, D-27, D-28, D-29, D- 30, D-31, D-32, D-33, D-34, D-35, D-36, D-37, D-38, D-39, D-40, D-41, D-42, D-43, D-44, D-45, D-46, D-47, D-48, D- 49, D-50, D-51, D-52, D-53, D-54, D-55, D-56, D-57, D-58, D-59, D-60, D-61, D-62, D-63, D-64, D-65, D-66, D-67, D- 68, D-69, D-70, D-71, D-72, D-73, D-74, D-75, D-76, D-77, D-78, D-79, D-80, D-81, D-82, D-83, D-84, D-85, D-86, D- 87, D-88, D-89, D-90, D-91, D-92, D-93, D-94, D-95, D-96, D-97, D-98, D-99, D-100, D-101, D-102, D-103, D-104, D- 105, D-106, D-107, D-108, D-109, D-110, D-111, D-112, D- 113, D-114, D-115, D-116, D-117, D-118, D-119, D-120, D- 121, D-122, D-123, D-124, D-125, D-126, D-127, D-128, D- 129, D-130, D-131, D-132, D-133, D-134, D-135, D-136, D- 137, D-138, D-139, D-140, D-141, D-142, D-143, D-144, D- 145, D-146, D-147, D-148, D-149, D-150, D-151, D-152, D- 153, D-154, D-155, D-156, D-157, D-158, D-159, D-160, D- 161, D-162, D-163, D-164, D-165, D-166, D-167, D-168, D- 169, D-170, D-171, D-172, D-173, D-174, D-175, D-176, D- 177, D-178, D-179, D-180, D-181, D-182, D-183, D-184, D- 185, D-186, D-187, D-188, D-189, D-190, D-191, D-192, D- 193, D-194, D-195, D-196, D-197, D-198, D-199, D-200, D- 201, D-202, D-203, D-204, D-205, D-206, D-207, D-208, D- 209, D-210, D-211, D-212, D-213, D-214, D-215, D-216, D- 217, D-218, D-219, D-220, D-221, D-222, D-223, D-224, D- 225, D-226, D-227, D-228, D-229, D-230, D-231, D-232, or a pharmaceutically acceptable salt or derivative or prodrug thereof.

8. The method of Embodiment 1 wherein the cyclooxygenase-2 nonselective inhibitor is D-1 to D-5, D-6 to D-10, D-11 to D-15, D-16 to D-20, D-21 to D-25, D-26 to D-30, D-31 to D-35, D-36 to D-40, D-41 to D-45, D-46 to D- 50, D-51 to D-55, D-56 to D-60, D-61 to D-65, D-66 to D- 70, D-71 to D-75, D-76 to D-80, D-81 to D-85, D-86 to D- 90, D-91 to D-95, D-96 to D-100, D-101 to D-105, D-106 to D-110, D-111 to D-115, D-116 to D-120, D-121 to D-125, D- 126 to D-130, D-131 to D-135, D-136 to D-140, D-141 to D- 145, D-146 to D-150, D-151 to D-155, D-156 to D-160, D-161 to D-165, D-166 to D-170, D-171 to D-175, D-176 to D-180, D-181 to D-185, D-186 to D-190, D-191 to D-195, D-196 to D-200, D-201 to D-205, D-206 to D-210, D-211 to D-215, D- 216 to D-220, D-221 to D-225, D-226 to D-230, D-231 to D- 232,, or a pharmaceutically acceptable salt or derivative or prodrug thereof.

9. The method of Embodiment 1 wherein the cyclooxygenase-2 selective inhibitor is selected from the group consisting of meloxicam, celecoxib, valdecoxib, deracoxib, rofecoxib, etoricoxib (MK-663), 4-cyclohexyl-5- [3-fluoro-4- (methylsulphonyl) phenyl]-2-methyl-oxazole (JTE-522), and 6- [ [5- (4-chlorobenzoyl)-1, 4-dimethyl-lH- pyrrol-2-yl] methyl-3 (2H)-pyridazinone (RS 57067), or a pharmaceutically acceptable salt or derivative or prodrug thereof.

10. The method of Embodiment 9 wherein the cyclooxygenase-2 selective inhibitor is celecoxib.

11. The method of Embodiment 9 wherein the cyclooxygenase-2 selective inhibitor is rofecoxib.

12. The method of embodiment 9 wherein parecoxib, CAS 198470-84-7, is employed as a prodrug and source of the cyclooxygenase-2 selective inhibitor valdecoxib.

13. The method of Embodiment 1 wherein the cyclooxygenase-2 selective inhibitor is a substituted benzopyran or a pharmaceutically acceptable salt or derivative or prodrug thereof.

14. The method of Embodiment 1 wherein the cyclooxygenase-2 selective inhibitor is a substituted benzopyran analog selected from the group consisting of substituted benzothiopyrans, dihydroquinolines, and dihydronaphthalenes, or a pharmaceutically acceptable salt or derivative or prodrug thereof.

15. The method of Embodiments 7-14 wherein the condition is selected from the group consisting of gout, pancreatitis, cholelithiasis, biliary obstruction, ulcerative colitis, Crohn's disease, coronary artery disease, aneurysm, arteriosclerosis, atherosclerosis, myocardial infarction, embolism, stroke, thrombosis, angina, coronary plaque inflammation, bacterial-induced inflammation, viral induced inflammation, and inflammation wherein the inflammation is associated with a surgical procedure involving an artery, a vein or a capillary.

16. The method of Embodiment 1 wherein the apical sodium bile acid transport inhibitor is a substituted benzothiepine compound.

17. The method of Embodiment 1 wherein the apical sodium bile acid transport inhibitor is a substituted benzothiazepine compound.

18. The method of Embodiments 16-17 wherein the condition is selected from the group consisting of gout, pancreatitis, cholelithiasis, biliary obstruction, ulcerative colitis, Crohn's disease, coronary artery disease, aneurysm, arteriosclerosis, atherosclerosis, myocardial infarction, embolism, stroke, thrombosis, angina, coronary plaque inflammation, bacterial-induced inflammation, viral induced inflammation, and inflammation wherein the inflammation is associated with a surgical procedure involving an artery, a vein or a capillary.

19. The method of Embodiment 1 further comprising treating the subject with an amount of an HMG-CoA reductase inhibitor wherein the amount of the apical sodium co-dependent bile acid transport inhibitor and the amount of the cyclooxygenase-2 selective inhibitor and the amount of the HMG-CoA reductase inhibitor together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the apical sodium co-dependent bile acid transport inhibitor, the cyclooxygenase-2 selective inhibitor and the HMG-CoA reductase inhibitor.

20. The method of Embodiment 19 wherein the HMG-CoA reductase inhibitor is selected from the group consisting of fluvastatin, lovastatin, pravastatin, simvastatin, atorvastatin, cerivastatin, bervastatin, rosuvastatin, and itavastatin, or a pharmaceutically acceptable salt or ester or lactone thereof.

21. The method of Embodiment 20 wherein the HMG-CoA reductase inhibitor is fluvastatin.

22. The method of Embodiment 20 wherein the HMG-CoA reductase inhibitor is lovastatin.

23. The method of Embodiment 20 wherein the HMG-CoA reductase inhibitor is pravastatin.

24. The method of Embodiment 20 wherein the HMG-CoA reductase inhibitor is simvastatin.

25. The method of Embodiment 20 wherein the HMG-CoA reductase inhibitor is atorvastatin.

26. The method of Embodiment 20 wherein the HMG-CoA reductase inhibitor is cerivastatin.

27. The method of Embodiment 20 wherein the HMG-CoA reductase inhibitor is bervastatin.

28. The method of Embodiment 20 wherein the HMG-CoA reductase inhibitor is rosuvastatin.

29. The method of Embodiment 20 wherein the HMG-CoA reductase inhibitor is itavastatin.

30. The method of Embodiments 19-29 wherein the condition is selected from the group consisting of gout, pancreatitis, cholelithiasis, biliary obstruction, ulcerative colitis, Crohn'S disease, coronary artery disease, aneurysm, arteriosclerosis, atherosclerosis, myocardial infarction, embolism, stroke, thrombosis, angina, coronary plaque inflammation, bacterial-induced inflammation, viral induced inflammation, and inflammation wherein the inflammation is associated with a surgical procedure involving an artery, a vein or a capillary.

31. A pharmaceutical combination comprising an amount of an apical sodium co-dependent bile acid transport inhibitor, an amount of a cyclooxygenase-2 selective inhibitor or prodrug, and a pharmaceutically acceptable carrier, wherein the amount of the apical sodium co-dependent bile acid transport inhibitor and the amount of the cyclooxygenase-2 selective inhibitor together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the apical sodium co- dependent bile acid transport inhibitor and the cyclooxygenase-2 selective inhibitor.

32. The combination of Embodiment 31 wherein the cyclooxygenase-2 selective inhibitor is D-1, D-2, D-3, D- 4, D-5, D-6, D-7, D-8, D-9, D-10, D-ll, D-12, D-13, D-14, D-15, D-16, D-17, celecoxib (D-18), D-19, D-20, rofecoxib (D-21), D-22, D-23, D-24, D-25, D-26, D-27, D-28, D-29, D- 30, D-31, D-32, D-33, D-34, D-35, D-36, D-37, D-38, D-39, D-40, D-41, D-42, D-43, D-44, D-45, D-46, D-47, D-48, D- 49, D-50, D-51, D-52, D-53, D-54, D-55, D-56, D-57, D-58, D-59, D-60, D-61, D-62, D-63, D-64, D-65, D-66, D-67, D- 68, D-69, D-70, D-71, D-72, D-73, D-74, D-75, D-76, D-77, D-78, D-79, D-80, D-81, D-82, D-83, D-84, D-85, D-86, D- 87, D-88, D-89, D-90, D-91, D-92, D-93, D-94, D-95, D-96, D-97, D-98, D-99, D-100, D-101, D-102, D-103, D-104, D- 105, D-106, D-107, D-108, D-109, D-110, D-lll, D-112, D- 113, D-114, D-115, D-116, D-117, D-118, D-119, D-120, D- 121, D-122, D-123, D-124, D-125, D-126, D-127, D-128, D- 129, D-130, D-131, D-132, D-133, D-134, D-135, D-136, D- 137, D-138, D-139, D-140, D-141, D-142, D-143, D-144, D- 145, D-146, D-147, D-148, D-149, D-150, D-151, D-152, D- 153, D-154, D-155, D-156, D-157, D-158, D-159, D-160, D- 161, D-162, D-163, D-164, D-165, D-166, D-167, D-168, D- 169, D-170, D-171, D-172, D-173, D-174, D-175, D-176, D-

177, D-178, D-179, D-180, D-181, D-182, D-183, D-184, D- 185, D-186, D-187, D-188, D-189, D-190, D-191, D-192, D- 193, D-194, D-195, D-196, D-197, D-198, D-199, D-200, D- 201, D-202, D-203, D-204, D-205, D-206, D-207, D-208, D- 209, D-210, D-211, D-212, D-213, D-214, D-215, D-216, D- 217, D-218, D-219, D-220, D-221, D-222, D-223, D-224, D- 225, D-226, D-227, D-228, D-229, D-230, D-231, D-232, or a pharmaceutically acceptable salt or derivative or prodrug thereof.

33. The combination of Embodiment 31 wherein the cyclooxygenase-2 selective inhibitor is D-1 to D-5, D-6 to D-10, D-11 to D-15, D-16 to D-20, D-21 to D-25, D-26 to D- 30, D-31 to D-35, D-36 to D-40, D-41 to D-45, D-46 to D- 50, D-51 to D-55, D-56 to D-60, D-61 to D-65, D-66 to D- 70, D-71 to D-75, D-76 to D-80, D-81 to D-85, D-86 to D- 90, D-91 to D-95, D-96 to D-100, D-101 to D-105, D-106 to D-110, D-111 to D-115, D-116 to D-120, D-121 to D-125, D- 126 to D-130, D-131 to D-135, D-136 to D-140, D-141 to D- 145, D-146 to D-150, D-151 to D-155, D-156 to D-160, D-161 to D-165, D-166 to D-170, D-171 to D-175, D-176 to D-180, D-181 to D-185, D-186 to D-190, D-191 to D-195, D-196 to D-200, D-201 to D-205, D-206 to D-210, D-211 to D-215, D- 216 to D-220, D-221 to D-225, D-226 to D-230, D-231 to D- 232, or a pharmaceutically acceptable salt or derivative or prodrug thereof.

34. The combination of Embodiment 31 wherein the cyclooxygenase-2 selective inhibitor is selected from the group consisting of meloxicam, celecoxib, valdecoxib, deracoxib, rofecoxib, etoricoxib (MK-663), 4-cyclohexyl-5- [3-fluoro-4- (methylsulphonyl) phenyl]-2-methyl-oxazole (JTE-522), and 6-[[5-(4-chlorobenzOyl)-1, 4-dimethyl-lH- pyrrol-2-yl] methyl]-3 (2H)-pyridazinone (RS 57067), or a pharmaceutically acceptable salt or derivative or prodrug thereof.

35. The combination of Embodiment 34 wherein the cyclooxygenase-2 selective inhibitor is celecoxib.

36. The combination of Embodiment 34 wherein the cyclooxygenase-2 selective inhibitor is rofecoxib.

37. The combination of embodiment 34 wherein parecoxib, CAS 198470-84-7, is employed as a prodrug and source of the cyclooxygenase-2 selective inhibitor valdecoxib.

38. The combination of Embodiment 31 wherein the cyclooxygenase-2 selective inhibitor is a substituted benzopyran or a pharmaceutically acceptable salt or derivative or prodrug thereof.

39. The combination of Embodiment 34 wherein the cyclooxygenase-2 selective inhibitor is a substituted benzopyran analog selected from the group consisting of substituted benzothiopyrans, dihydroquinolines, and dihydronaphthalenes, or a pharmaceutically acceptable salt or derivative or prodrug thereof.

40. The combination of Embodiment 31 wherein the apical sodium bile acid transport inhibitor is a substituted benzothiepine compound.

41. The combination of Embodiment 31 wherein the apical sodium bile acid transport inhibitor is a substituted benzothiazepine compound.

42. A process for preparing the pharmaceutical combination of Embodiment 31 comprising combining an amount

of the apical sodium co-dependent bile acid transport inhibitor, an amount of a cyclooxygenase-2 selective inhibitor or prodrug, and a pharmaceutically acceptable carrier.

43. The combination of Embodiment 31 further comprising an amount of an HMG-CoA reductase inhibitor wherein the amount of the apical sodium co-dependent bile acid transport inhibitor, the amount of the cyclooxygenase-2 selective inhibitor and the amount of the HMG-CoA reductase inhibitor together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the apical sodium co-dependent bile acid transport inhibitor and the cyclooxygenase-2 selective inhibitor and the HMG- CoA reductase inhibitor.

44. The combination of Embodiment 43 wherein the HMG- CoA reductase inhibitor is selected from the group consisting of fluvastatin, lovastatin, pravastatin, simvastatin,, atorvastatin, cerivastatin, bervastatin, rosuvastatin, and itavastatin, or a pharmaceutically acceptable salt or ester or lactone thereof.

45. The combination of Embodiment 44 wherein the HMG- CoA reductase inhibitor is fluvastatin.

46. The combination of Embodiment 44 wherein the HMG- CoA reductase inhibitor is lovastatin.

47. The combination of Embodiment 44 wherein the HMG- CoA reductase inhibitor is pravastatin.

48. The combination of Embodiment 44 wherein the HMG- CoA reductase inhibitor is simvastatin.

49. The combination of Embodiment 44 wherein the HMG- CoA reductase inhibitor is atorvastatin.

50. The combination of Embodiment 44 wherein the HMG- CoA reductase inhibitor is cerivastatin.

51. The combination of Embodiment 44 wherein the HMG- CoA reductase inhibitor is bervastatin.

52. The combination of Embodiment 44 wherein the HMG- CoA reductase inhibitor is rosuvastatin.

53. The combination method of Embodiment 44 wherein the HMG-CoA reductase inhibitor is itavastatin.

54. The process of Embodiment 42 further comprising combining an amount of an HMG-CoA reductase inhibitor, an amount of the apical sodium co-dependent bile acid transport inhibitor, an amount of a cyclooxygenase-2 selective inhibitor or prodrug, and a pharmaceutically acceptable carrier.

55. A kit comprised of an amount of an apical sodium co-dependent bile acid transport inhibitor in a dosage formulation and an amount of a cyclooxygenase-2 selective inhibitor or prodrug in a separate dosage formulation wherein the amount of the apical sodium co-dependent bile acid transport inhibitor and the amount of the cyclooxygenase-2 selective inhibitor together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the

apical sodium co-dependent bile acid transport inhibitor and the cyclooxygenase-2 selective inhibitor.

56. The kit of Embodiment 55 wherein the cyclooxygenase-2 selective inhibitor is D-1, D-2, D-3, D- 4, D-5, D-6, D-7, D-8, D-9, D-10, D-ll, D-12, D-13, D-14, D-15, D-16, D-17, celecoxib (D-18), D-19, D-20, rofecoxib (D-21), D-22, D-23, D-24, D-25, D-26, D-27, D-28, D-29, D- 30, D-31, D-32, D-33, D-34, D-35, D-36, D-37, D-38, D-39, D-40, D-41, D-42, D-43, D-44, D-45, D-46, D-47, D-48, D- 49, D-50, D-51, D-52, D-53, D-54, D-55, D-56, D-57, D-58, D-59, D-60, D-61, D-62, D-63, D-64, D-65, D-66, D-67, D- 68, D-69, D-70, D-71, D-72, D-73, D-74, D-75, D-76, D-77, D-78, D-79, D-80, D-81, D-82, D-83, D-84, D-85, D-86, D- 87, D-88, D-89, D-90, D-91, D-92, D-93, D-94, D-95, D-96, D-97, D-98, D-99, D-100, D-101, D-102, D-103, D-104, D- 105, D-106, D-107, D-108, D-109, D-110, D-lll, D-112, D- 113, D-114, D-115, D-116, D-117, D-118, D-119, D-120, D- 121, D-122, D-123, D-124, D-125, D-126, D-127, D-128, D- 129, D-130, D-131, D-132, D-133, D-134, D-135, D-136, D- 137, D-138, D-139, D-140, D-141, D-142, D-143, D-144, D- 145, D-146, D-147, D-148, D-149, D-150, D-151, D-152, D- 153, D-154, D-155, D-156, D-157, D-158, D-159, D-160, D- 161, D-162, D-163, D-164, D-165, D-166, D-167, D-168, D- 169, D-170, D-171, D-172, D-173, D-174, D-175, D-176, D- 177, D-178, D-179, D-180, D-181, D-182, D-183, D-184, D- 185, D-186, D-187, D-188, D-189, D-190, D-191, D-192, D- 193, D-194, D-195, D-196, D-197, D-198, D-199, D-200, D- 201, D-202, D-203, D-204, D-205, D-206, D-207, D-208, D- 209, D-210, D-211, D-212, D-213, D-214, D-215, D-216, D- 217, D-218, D-219, D-220, D-221, D-222, D-223, D-224, D- 225, D-226, D-227, D-228, D-229, D-230, D-231, D-232, or a pharmaceutically acceptable salt or derivative or prodrug thereof.

57. The kit of Embodiment 55 wherein the cyclooxygenase-2 selective inhibitor is D-1 to D-5, D-6 to

D-10, D-11 to D-15, D-16 to D-20, D-21 to D-25, D-26 to D- 30, D-31 to D-35, D-36 to D-40, D-41 to D-45, D-46 to D- 50, D-51 to D-55, D-56 to D-60, D-61 to D-65, D-66 to D- 70, D-71 to D-75, D-76 to D-80, D-81 to D-85, D-86 to D- 90, D-91 to D-95, D-96 to D-100, D-101 to D-105, D-106 to D-110, D-111 to D-115, D-116 to D-120, D-121 to D-125, D- 126 to D-130, D-131 to D-135, D-136 to D-140, D-141 to D- 145, D-146 to D-150, D-151 to D-155, D-156 to D-160, D-161 to D-165, D-166 to D-170, D-171 to D-175, D-176 to D-180, D-181 to D-185, D-186 to D-190, D-191 to D-195, D-196 to D-200, D-201 to D-205, D-206 to D-210, D-211 to D-215, D- 216 to D-220, D-221 to D-225, D-226 to D-230, D-231 to D- 232, or a pharmaceutically acceptable salt or derivative or prodrug thereof.

58. The kit of Embodiment 55 wherein the cyclooxygenase-2 selective inhibitor is selected from the group consisting of meloxicam, celecoxib, valdecoxib, deracoxib, rofecoxib, etoricoxib (MK-663), 4-cyclohexyl-5- [3-fluoro-4- (methylsulphonyl) phenyl]-2-methyl-oxazole (JTE-522), and 6- [ (5- (4-chlorobenzoyl)-1, 4-dimethyl-1H- pyrrol-2-yl] methyl]-3 (2H)-pyridazinone (RS 57067), or a pharmaceutically acceptable salt or derivative or prodrug thereof.

59. The kit of Embodiment 58 wherein the cyclooxygenase-2 selective inhibitor is celecoxib.

60. The kit of Embodiment 58 wherein the cyclooxygenase-2 selective inhibitor is rofecoxib.

61. The kit of embodiment 58 wherein parecoxib, CAS 198470-84-7, is employed as a prodrug and source of the cyclooxygenase-2 selective inhibitor valdecoxib.

62. The kit of Embodiment 55 wherein the cyclooxygenase-2 selective inhibitor is a substituted benzopyran or a pharmaceutically acceptable salt or derivative or prodrug thereof.

63. The kit of Embodiment 55 wherein the cyclooxygenase-2 selective inhibitor is a substituted benzopyran analog selected from the group consisting of substituted benzothiopyrans, dihydroquinolines, and dihydronaphthalenes, or a pharmaceutically acceptable salt or derivative or prodrug thereof.

64. The kit of Embodiment 55 wherein the apical sodium bile acid transport inhibitor is a substituted benzothiepine compound.

65. The kit of Embodiment 55 wherein the apical sodium bile acid transport inhibitor is a substituted benzothiazepine compound.

66. The kit of Embodiment 55 further comprising an amount of an HMG-CoA reductase inhibitor wherein the amount of the apical sodium co-dependent bile acid transport inhibitor, the amount of the cyclooxygenase-2 selective inhibitor and the amount of the HMG-CoA reductase inhibitor together constitute a hypercholesterolemia-related condition effective amount or an inflammation-related condition effective amount of the apical sodium co-dependent bile acid transport inhibitor, the cyclooxygenase-2 selective inhibitor and the HMG-CoA reductase inhibitor.

67. The kit of Embodiment 66 wherein the HMG-CoA reductase inhibitor is selected from the group consisting

of fluvastatin, lovastatin, pravastatin, simvastatin, atorvastatin, cerivastatin, bervastatin, rosuvastatin, and itavastatin, or a pharmaceutically acceptable salt or ester or lactone thereof.

68. The kit of Embodiment 67 wherein the HMG-CoA reductase inhibitor is fluvastatin.

69. The kit of Embodiment 67 wherein the HMG-CoA reductase inhibitor is lovastatin.

70. The kit of Embodiment 67 wherein the HMG-CoA reductase inhibitor is pravastatin.

71. The kit of Embodiment 67 wherein the HMG-CoA reductase inhibitor is simvastatin.

72. The kit of Embodiment 67 wherein the HMG-CoA reductase inhibitor is atorvastatin.

73. The kit of Embodiment 67 wherein the HMG-CoA reductase inhibitor is cerivastatin.

74. The kit of Embodiment 67 wherein the HMG-CoA reductase inhibitor is bervastatin.

75. The kit of Embodiment 67 wherein the HMG-CoA reductase inhibitor is rosuvastatin.

76. The kit of Embodiment 67 wherein the HMG-CoA reductase inhibitor is itavastatin.

77. A method for treating or preventing a hypercholesterolemia-related or an inflammation-related

condition in a subject in need of such treatment or prevention, comprising treating the subject with an amount of an apical sodium co-dependent bile acid transport inhibitor and an amount of a chromene cyclooxygenase-2 selective inhibitor or prodrug, wherein the amount of the apical sodium co-dependent bile acid transport inhibitor and the amount of the chromene cyclooxygenase-2 selective inhibitor together constitute a hypercholesterolemia- related condition effective amount or an inflammation- related condition effective amount of the apical sodium co-dependent bile acid transport inhibitor and the chromene cyclooxygenase-2 selective inhibitor.

78. A method for treating or preventing a hypercholesterolemia-related or an inflammation-related condition in a subject in need of such treatment or prevention, comprising treating the subject with an amount of an HMG Co-A reductase inhibitor and an amount of a chromene cyclooxygenase-2 selective inhibitor or prodrug, wherein the amount of the HMG Co-A reductase inhibitor and the amount of the chromene cyclooxygenase-2 selective inhibitor together constitute a hypercholesterolemia- related condition effective amount or an inflammation- related condition effective amount of the HMG Co-A reductase inhibitor and the chromene cyclooxygenase-2 selective inhibitor.

The examples herein can be performed by substituting the generically or specifically described therapeutic compounds or inert ingredients for those used in the preceding examples.

The invention being thus described, it is apparent that the same can be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the present invention, and all such modifications and equivalents as would be obvious to one skilled in the art are intended to be included within the scope of the following claims.