Background of the Invention Elevated serum cholesterol levels (>200mg/dL) have been indicated as a major risk factor for heart disease, the leading cause of death among Americans. As a result, experts have recommended that those individuals at high risk decrease serum cholesterol levels through dietary changes, a program of physical exercise, and lifestyle changes. It is recommended that the intake of saturated fat and dietary cholesterol be strictly limited and that soluble fiber consumption be increased. Strictly limiting the intake of saturated fat and cholesterol does not, itself, present a risk to proper health and nutrition. Even where saturated fat and cholesterol are severely restricted from the diet, the liver remains able to synthesize sufficient quantities of cholesterol to perform necessary bodily functions.

More recently, experts have begun to examine the individual components of the lipid profile, in addition to the total cholesterol level (TC). While an elevated TC is a risk factor, the levels of the various forms of cholesterol which make up TC may also be risk factors. Elevated low-density lipoprotein (LDL) is a cause for concern, as these loosely packed lipoproteins are more likely to lodge within the cardiovascular system leading to the formation of plaque. Low levels of high-density lipoproteins (HDL) are an additional risk factor, as they serve to sweep artery clogging cholesterol from the blood stream. A better indication of risk appears to be the ratio of TC: HDL.

A number of nutritional factors have been shown to improve serum cholesterol levels. For example, the use of phytosterols has been well documented in human clinical trials and in animal studies to lower serum cholesterol levels. This cholesterol lowering effect has been attributed to interference with the absorption of dietary cholesterol. Phytosterols, being structurally similar to cholesterol, competitively bind with cholesterol sterol receptor sites, thus preventing cholesterol uptake. Unlike their cholesterol counterparts, phytosterols are very poorly absorbed, and some are not absorbed at all. Therefore, phytosterols do not contribute to an increase in serum cholesterol levels.

In addition to competing for receptor sites, phytosterols also compete for the enzyme cholesterol esterase. This enzyme is required by cholesterol for its breakdown to components which may be absorbed through the microvilli which line the wall of the small intestine. Thus, phytosterols also impede the enzymatic breakdown and intestinal absorption of cholesterol, which further reduces serum cholesterol levels.

Plant derived long-chained aliphatic alcohols have also been documented to reduce serum cholesterol levels in experimental models, healthy humans and in type II hypercholesterolemic patients. These aliphatic alcohols, collectively known as policosanol, have been employed in the treatment of elevated serum cholesterol levels in only the past five years, but policosanol has shown much promise, as reported in a number of published human clinical trials. The mechanism of action has not yet been elucidated, but policosanol's effectiveness is attributed to its influence on the bio-synthesis of cholesterol within the liver. This accounts for the ability of policosanol not only to decrease total cholesterol, but also to decrease LDL serum levels and increase HDL levels.

Summary of the Invention The present invention provides a composition for reducing serum cholesterol levels in humans and animals. The composition comprises from about 5% to about 75% by weight of phytosterol, and from about 1% to about 60% by weight of policosanol. The composition further comprises from 0% to about 65% by weight of pharmaceutically acceptable formulation aids, such as diluents, stabilizers, binders, buffers, lubricants, coating agents, preservatives, emulsifiers and suspension agents.

In a preferred embodiment, the composition comprises from about 10% to about 60% by weight of phytosterol, and from about 3% to about 46% by weight of policosanol. In the most preferred embodiment of the invention, the composition comprises about 3.2: 1 parts by weight of phytosterol and policosanol.

Detailed Description of the Invention As noted previously, policosanol is a mixture of high-molecular weight aliphatic alcohols. These alcohols occur naturally in wax form and are characterized by fatty alcohol chains ranging from 20 to 39 carbon atoms in length. The major component of policosanol are the aliphatic alcohols octacosanol and triacontanol. Policosanol is isolated from a number of different plant sources, including sugar cane wax and rice bran wax. The policosanol used in the preferred embodiment of the invention is obtained from rice bran wax and has the formulation set forth below in Table I. This material is sold under the name"Rice Bran Wax"and is available from Traco Labs, Inc. It should be understood, however, that the invention is not limited in this regard and that policosanol commonly available from other naturally occurring sources may be utilized.

Table I Rice Bran Wax typical long-chain aliphatic alcohol profile: Carbon Fatty Alcohol Composition (%) C220H Docosanol (Behenyl Alcohol) 0.36 C240H Tetracosanol (Lignoceryl Alcohol) 3.21 C260H Hexacosanol (Cerotyl Alcohol) 2.93 C28°H Octacosanol (Montanyl Alcohol) 5.59 C30°H Triacontanol (Melissyl Alcohol) 8.35 C320H Dotriacontanol 4.64 C340H Tetratriacontanol 2.22 C360H Hexatriacontanol. 50 Total policosanols 23-33% Phytosterols are also mixtures of long-chained aliphatic alcohols in a wax form. They are naturally occurring in many common vegetable food products. The particular phytosterol used in the preferred embodiment of the invention is derived from vegetable oil and has the formulation set forth in Table II. This material is sold under the trademark"CHOLESTATIN"and is available from Traco Labs, Inc. Again, however, it should be understood that the invention is not limited to this particular phytosterol product, and that any number of other commonly available phytosterols can be used.

Table II Phytosterol composition: Total sterols 88% Min.

Assav Specification B-Sitosterol 43% Min. campesterol 25% Min. stigmasterol 15% Min.

As noted previously, phytosterol and policosanol lower serum cholesterol links by two independent and unrelated mechanisms of action. However, both compounds together are expected to have a synergistic effect on lowering serum cholesterol. As previously mentioned, phytosterols impede the enzymatic breakdown and intestinal absorption of cholesterol, which reduces serum cholesterol levels. Policosanol acts directly on the cholesterol synthesis pathway itself, thereby inhibiting the bio-synthesis of cholesterol from saturated fat. However, both compounds together are expected to have a synergistic effect on lowering serum cholesterol levels. Thus, the combination of both phytosterol and policosanol into a single composition is expected to provide a more effective treatment for elevated serum cholesterol than would be expected from the additive effect of both components.

Examples of compositions made according to the invention is set forth below: Example 1: tablet formula: ingredient amt/cap function "CHOLESTATIN" (Min. 88% phytosterols) 250mg active "Rice Bran Wax" (23-33% policosanols) 250mg active Calcium phosphate 261.7mg base Cellulose 49.4mg tablet coating agent Stearic acid 23.8mg lubricant Magnesium stearate 6.8mg lubricant Silicon dioxide 9.4mg diluent Example 2 : Soft gelatin capsule formulation: ingredient amt/cag function "CHOLESTATIN" (Min. 88% phytosterols) 250mg active "Rice Bran Wax" (23-33% policosanols) 250mg active Medium Chain Triglycerides 700mg diluent/emulssifying suspending agent Previous clinical and toxicological testing of policosanol and phytosterol has shown that the tolerance of both components is good. Significantly larger doses of both waxes are readily tolerated. Occasional GI irritation might be expected at extremely high doses, far greater than the normal dosage range. In the event such irritation should occur, it would be expected to be minimal, and would not pose any risk to health.

Toxicology performed on the 50% phytosterol/50% rice bran wax composition has proven that the composition is non-toxic at an oral dose of 5000mg/kg of body weight in Sprague-Dawley rats. Accordingly, oral dosages in humans of up to a maximum dosage of 1500 mg administered three times per day is considered appropriate.

While preferred embodiments have been shown and described, various modifications and substitutions may be made without departing from the spirit and scope of the invention. Accordingly, it is to be understood that the present invention has been described by way of example and not by limitation.