BACKGROUNDART Renal insufficient patients have difficulties in excretion of phosphate to urine. Accumulated phosphate in the patient causes central and peripheral neuropathy, cardiomyopathy, hyperlipidemia, glycometabolism disorder, pruritus, anemia, hypogonadism, disorder for diffusing of the lung, arteriosclerosis, immunodeficiency, renal failure, etc. (Jin to Touseki, 37, 2: 3211994). Even during dialysis, those pathemas and complications cannot be dissolved. Therefore, it is essential for the renal insufficient patients to treat hyperphosphoremia.

Currently, dietotherapy and/or administration of a peroral phosphate adsorbent are applied for treating hyperphosphoremia. However, the dietotherapy is not effective for decreasing the amount of phosphate in the blood because it is inevitable for the patient to have some amount of proteins in the ingesta.

As the peroral phosphate adsorbents, aluminum preparation (e. g., aluminum hydroxide), calcium preparation (e. g., calcium carbonate, calcium acetate), magnesium preparation (e. g., magnesium carbonate) and anion-exchange resins (e. g., Rena Gel (D, manufactured by Chugai Pharmaceutical Co., Ltd. and Kirin Brewery Company, Limited) are used.

Among these phosphate adsorbents, the aluminum preparation, calcium preparation and magnesium preparation are adsorbed through the intestine and tend to accumulate in the body, and the anion- exchange resins tend to cause side effects such as constipation, diarrhea, flatus, nausea, emesis, etc. And further, the dose of the anion- exchange resins is so large due to low ability of adsorption that

intensifies such side effects.

DISCLOSURE OF INVENTION Accordingly, an object of this invention is to provide a kind of novel polymers having ability for adsorbing phosphate. Since the polymer of the present invention has stronger ability of adsorption, the dosage of the polymer can be reduced.

Another object of this invention is to provide a pharmaceutical composition containing a polymer as an active ingredient.

Further object of this invention is to provide a use of the polymers for treating or preventing hyperphosphoremia.

The novel polymers of this. invention have ability for adsorbing phosphate and can be obtained by polymerization of a monomer of the formula (I) or its salt in the presence of a radical initiator, or by polymerization of a monomer of the formula (I) or its salt with a monomer of the formula (II) or its salt in a molar ratio of (I): (II) being 1: 0.1 to 1: 25 in the presence of a radical initiator wherein Rl and R3 are each hydrogen atom or lower alkyl group, R2 and R4 are each acyl group, aliphatic silyl group, amino lower alkyl group which may have one or more suitable substituent (s), heterocyclic group which may have one or more suitable substituent (s) or carboxy group which may be esterified by the residue of cellulose optionally substituted with one or more lower alkyl and/or lower alkenoyl.

In the above and subsequent descriptions of the present specification and claims, suitable examples and illustrations of the various definitions which the present invention includes within the scope are explained in detail in the following.

The term"lower"is intended to mean a group having 1 to 6 carbon atom (s), unless otherwise indicated.

Examples of"one or more"are the numbers of 1 to 6, in which the preferred one is the number of 1 to 3, and the most preferred one is the number of 1 or 2.

Preferred examples of"halogen"are fluorine, chlorine, bromine, iodine and the like.

Preferred examples of"lower alkoxy"moiety include straight or branched ones such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, pentyloxy, tert-pentyloxy, neo-pentyloxy, hexyloxy, isohexyloxy or the like.

Preferred examples of"lower alkyl"moiety include straight or branched ones having 1 to 6 carbon atom (s), such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, tert- pentyl, neo-pentyl, hexyl, isohexyl or the like.

Preferred examples of"aryl"and"ar"moiety include phenyl which may have lower alkyl (e. g., phenyl, mesityl, xylyl or tolyl), naphthyl, anthryl, indanyl, fluorenyl or the like, and this"aryl"and"ar"moiety may have one or more halogen.

Preferred examples of"aroyl"include benzoyl, toluoyl, naphthoyl, anthrylcarbonyl and the like.

Preferred examples of"heterocyclic group"or"heterocyclic" moiety : unsaturated 3-to 8-membered (more preferably 5-or 6-membered) heteromonocyclic groups containing 1 to 4 nitrogen atom (s), for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, dihydropyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl (e. g., 4H-1, 2,4-triazolyl, 1H- 1,2,3-triazolyl or 2H-1, 2,3-triazolyl), and tetrazolyl (e. g., 1H-tetrazolyl or 2H-tetrazolyl); saturated 3-to 8-membered (more preferably 5-or 6-membered)

heteromonocyclic groups containing 1 to 4 nitrogen atom (s), for example, pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl and azetidinyl; unsaturated condensed heterocyclic groups containing 1 to 4 nitrogen atom (s), for example, indolyl, isoindolyl, indolinyl, indolizinyl, benzimidazolyl, quinolyl, isozuinolyl, indazolyl and benzotriazolyl ; unsaturated 3-to 8-membered (more preferably 5-or 6-membered) heteromonocyclic groups containing 1 or 2 oxygen atom (s) and 1 to 3 nitrogen atom (s), for example, oxazolyl, isoxazolyl and oxadiazolyl (e. g., 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl or 1,2,5-oxadiazolyl); saturated 3-to 8-membered (more preferably 5-or 6-membered) heteromonocyclic groups containing 1 or 2 oxygen atom (s) and 1 to 3 nitrogen atom (s), for example, morpholinyl, sydnonyl and morpholino; unsaturated condensed heterocyclic groups containing 1 or 2 oxygen atom (s) and 1 to 3 nitrogen atom (s), for example, benzoxazolyl and benzoxadiazolyl; unsaturated 3-to 8-membered (more preferably 5-or 6-membered) heteromonocyclic groups containing 1 or 2 sulfur atom (s) and 1 to 3 nitrogen atom (s), for example, thiazolyl, isothiazolyl, thiadiazolyl (e. g., 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl or 1,2,5- thiadiazolyl) and dihydrothiazinyl; saturated 3-to 8-membered (more preferebly 5-or 6-membered) heteromonocyclic groups containing 1 or 2 sulfur atom (s) and 1 to 3 nitrogen atom (s), for example thiazolidinyl, thiomorpholinyl and thiomorpholino ; unsaturated 3-to 8-membered (more preferably 5-or 6-membered) heteromonocyclic groups containing 1 or 2 sulfur atom (s), for example, thienyl, dihydrodithiinyl and dihydrodithionyl; unsaturated condensed heterocyclic groups containing 1 or 2 sulfur atom (s) and 1 to 3 nitrogen atom (s), for example, benzothiazolyl, benzothiadiazolyl and imidazothiadiazolyl ; unsaturated 3-to 8-membered (more preferably 5-or 6-membered) heteromonocyclic groups containing an oxygen atom, for example furyl; saturated 3-to 8-membered (more preferably 5-or 6-membered) heteromonocyclic groups containing 1 or 2 oxygen atom (s), for example, tetrahydrofuran, tetrahydropyran, dioxacyclopentane and

dioxacyclohexane; unsaturated 3-to 8-membered (more preferably 5-or 6-membered) heteromonocyclic groups containing an oxygen atom and 1 ot 2 sulfur atom (s), for example, dihydrooxathiinyl; unsaturated condensed heterocyclic groups containing 1 or 2 sulfur atom (s), for example, benzothienyl and benzodithiinyl; unsaturated condensed heterocyclic group containing an oxygen atom and 1 or 2 sulfur atom (s), for example, benzoxathiinyl; and the like, and this"heterocyclic group"may have one or more suitable substituent (s) selected from the group consisting of sulfo, lower alkyl, oxo, halogen and hydroxy.

Preferred examples of"acyl group"include aliphatic acyl, aromatic acyl, arylaliphatic aciyl and heterocyclic-aliphatic acyl derived from carboxylic acid, carbonic acid, carbamic acid and sulfonic acid.

More preferred examples of the"acyl group"are illustrated as follows: carboxy; carbamoyl; mono or di (lower) alkylcarbamoyl (e. g., methylcarbamoyl, dimethylcarbamoyl, ethylcarbamoyl, diethylcarbamoyl, propylcarbamoyl, n-butylcarbamoyl or 1,1- dimethylcarbamoyl) ; aliphatic acyl such as lower or higher alkanoyl (e. g., formyl, acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 2,2- dimethylpropanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, undecanoyl, dodecanoyl, tridecanoyl, tetradecanoyl, pentadecanoyl, hexadecanoyl, heptadecanoyl, octadecanoyl, nonadecanoyl or icosanoyl); lower or higher alkoxycarbonyl (e. g., methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, n-butoxycarbonyl, tert-butoxycarbonyl, tert- pentyloxycarbonyl, hexyloxycarbonyl or heptyloxycarbonyl) ; lower alkenyloxycarbonyl (e. g., vinyloxycarbonyl, propenyloxycarbonyl, allyloxycarbonyl, butenyloxycarbonyl, butedienyloxycarbonyl, pentenyloxycarbonyl or hexenyloxycarbonyl); lower or higher alkylsulfonyl (e. g., methylsulfonyl or ethylsulfonyl); lower or higher alkoxysulfonyl (e. g., methoxysulfonyl or ethoxysulfonyl); aromatic acyl such as aroyl (e. g., benzoyl, toluoly or naphthoyl);

ar (lower) alkanoyl [e. g., phenyl (Ci-C6) alkanoyl (e. g., phenylacethyl, phenylpropanoyl, phenylbutanoyl, phenylisobutanoyl, phenylpentanoyl or phenylhexanoyl), or naphthyl (Cl-C6) alkanoyl (e. g., naphthylacetyl, naphthylpropanoyl or naphthylbutanoyl)] ; ar (lower) alkenoyl [e. g., phenyl (C3-C6) alkenoyl (e. g., phenylpropenoyl, phenylbutenoyl, phenylmethacryloyl, phenylpentanoyl or phenylhexenoyl), or naphthyl (C3-C6) alkenoyl (e. g., naphthylpropenoyl or naphthylbutenoyl)] ; ar (lower) alkoxycarbonyl [e. g., phenyl (Cl-C6) alkoxycarbonyl (e. g., benzyloxycarbonyl), or fluorenyl (Ci-C6) alkoxycarbonyl (e. g., fluorenylmethyloxycarbonyl)] ; aryloxycarbonyl (e. g., phenoxycarbonyl or naphthyloxycarbonyl); aryloxy (lower) alkanoyl (e. g., phenoxyacetyl or phenoxypropionyl) ; arylcarbamoyl (e. g., phenylcarbamoyl); arylthiocarbamoyl (e. g., phenylthiocarbamoyl); arylglyoxyloxy (e. g., phenylglyoxyloyl or naphthylglyoxyloyl); arylsulfonyl which may have 1 to 4 lower alkyl (e. g., phenylsulfonyl or p-tolylsulfonyl); aroyl (e. g., benzoyl) substituted with one or more suitable substituent (s); heterocyclic aryl such as heterocycliccarbonyl ; heterocyclicoxycarbonyl; heterocyclic (lower) alkanoyl (e. g., heterocyclicacetyl, heterocyclicpropanoyl, heterocyclicbutanoyl, heterocyclicpentanoyl or heterocyclichexanoyl) ; heterocyclic (lower) alkenoyl (e. g., heterocyclicpropenoyl, heterocyclicbutenoyl, heterocyclicpentenoyl or heterocyclichexenoyl) ; heterocyclicglyoxyloyl ; and the like, in which suitable"heterocyclic"moieties in the terms "heterocycliccarbonyl","heterocyclicoxycarbonyl", "heterocyclic (lower) alkanoyl","heterocyclic (lower) alkenoyl" and "heterocyclicglyoxyloyl"can be referred to aforementioned"heterocyclic" moieties.

Preferred examples of the lower alkyl group for RI and R3 are referred to aforementioned"lower alkyl", in which the more preferred

ones are methyl, ethyl, propyl, n-butyl, t-butyl, pentyl and n-hexyl.

Preferred examples of the acyl group for R2 and R4 can be referred to aforementioned"acyl group", in which the more preferred ones are lower alkylcarbamoyl group such as methylcarbamoyl, dimethylcarbamoyl, ethylcarbamoyl, propylcarbamoyl, n- butylcarbamoyl, pentylcarbamoyl, hexylcarbamoyl and 1,1- dimethylethylcarbamoyl ; arylcarbamoyl group such as phenylcarbamoyl and naphthylcarbamoyl ; lower alkoxycarbonyl group such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, n-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl ; aforementioned heterocyclicoxycarbonyl group, in which the preferred ones are quinolinyloxycarbonyl, pyridyloxycarbonyl and furyloxycarbonyl; and aforementioned heterocycliccarbonyl group, in which the oreferred ones are morpholinylcarbonyl, pyridylcarbonyl, furoyl, thenoyl and imidazoylcarbonyl.

Preferred examples of the aliphatic silyl group for R2 and R4 are trimethylsilyl and triethylsilyl.

Preferred examples of the amino (lower) aLkyl group for R2 and R4 are aminomethyl, aminoethyl, aminopropyl, amino-n-butyl, aminopentyl and aminohexyl.

Preferred examples for the heterocyclic group for R2 and R4 can be referred to aforementioned"heterocyclic group", in which the more preferred ones are pyridyl, thienyl, furyl, pyrolyl, thiazolyl, oxazolyl, isoxazolyl and quinolyl.

The above lower alkylcarbamoyl group, arylcarbamoyl group, lower alkoxycarbonyl group, heterocyclicoxycarbonyl group, heterocycliccarbonyl group, amino (lower) alkyl group and heterocyclic group may have one or more substituent (s) selected from the group consisting of sulfo; hydroxy; carboxy; amino ; sulfo (lower) alkyl- di (lower) alkylamino such as sulfopropyl-dimethylamino, sulfomethyl- dimethylamino and sulfoethyl-dimethylamino; carboxy (lower) alkylamino such as carboxymethyl-dimethylamino ;

dihydroxyboraneyl; tri (lower alkyl) ammonium such as trimethylammonium; glycosyloxy ; heterocyclic carbonylamino such as (2-oxo-1,2-dihydro-4-pyrimidinyl) carbonylamino, (2,4-dioxo-3,4- dihydro-1 (2H)-pyrimidinyl) carbonylamino and (5-fluoro-2,4-dioxo-3,4- dihydro-1 (2H)-pyrimidinyl) carbonylamino; heterocyclic (lower) alkylaminocarbonylamino such as 2- (lH-imidazol-5- yl) ethylaminocarbonylamino ;- (lower alkoxy) s-lower alkoxy such as- (OCH2CH2) 8-OCH3 ; and halogen such as chlorine and bromine.

The preferred polymer of the invention can be obtained by polymerization of a monomer of the formula (I) or its salt in. the presence of a radical initiator, or by polymerization of a monomer of the formula (I) or its salt with a monomer of the formula (II) or its salt in a molar ratio of (I) : (II) being 1: 0.1 to 1: 25, preferably 1: 0.5 to 1: 20 in the presence of a radical initiator wherein R1 and R3 are each as defined in the above, and R2 and R4 are each lower alkyl carbamoyl group, aryl carbamoyl group, lower alkoxycarbonyl group, heterocyclicoxycarbonyl group or heterocyclccarbonyl group, each of which may have one or more suitable substituent (s); tri (lower) alkylsilyl group; amino lower alkyl group which may have one or more suitable substituent (s); heterocyclic group which may have one or more suitable substituent (s); or carboxy group which may be esterified by the residue of cellulose optionally substituted with one or more lower alkyl and/or lower

alkenoyl.

The more preferred polymer of the invention can be obtained by polymerization of a monomer of the formula (I) or its salt in the presence of a radical initiator, or by polymerization of a monomer of the formula (I) or its salt with a monomer of the formula (II) or its salt in a molar ratio of (I) : (II) being 1: 0.1 to 1: 25, preferably 1: 0.5 to 1: 20 in the presence of a radical initiator wherein RI and R3 are each as defined in the above, and R2 and R4 are each lower alkyl carbamoyl group which may have one or more substituents selected from the group consisting of sulfo, hydroxy, carboxy, amino, sulfo (lower) alkylamino and carboxy (lower) alkylamino, or lower alkoxycarbonyl group which may have one or more substituents selected from the group consisting of hydroxy, amino, lower alkylamino, glycosyloxy, heterocyclic carbonylamino and heterocyclic (lower) alkylaminocarbonylamino; tri (lower) alkylsilyl group; amino lower alkyl group which may have one or more suitable substituent (s); heterocyclic group which may have one or more substituent (s); or carboxy group which may be esterified by the residue of cellulose optionally substituted with one or more lower alkyl and/or lower alkenoyl.

Suitable salts of the polymers, monomers of the formula (I), the formula (Ia) and the formula (II) are conventional non-toxic salts such as salt with an alkali metal [e. g., lithium, sodium or potassium] and an alkaline earth metal le. g., calcium or magnesium], ammonia, an

organic base [e. g., trimethylamine, triethylamine, pyridine, picoline, dicyclohexylamine or N, N'-dibenzylethylenediamine], an organic acid [e. g., formic acid, acetic acid, trifluoroacetic acid, maleic acid, tartaric acid, oxalic acid, methanesulfonic acid, benzenesulfonic acid or toluenesulfonic acid], an inorganic acid [e. g., hydrochloric acid, hydrobromic acid, sulfuric acid or phosphoric acid], an amino acid [e. g., arginine, aspartic acid or glutamic acid] or the like.

The preferred monomers of the formula (I) and the formula (II) are 2-glucosylethyl methacrylate (GEMA), N- tris (hydroxymethyl) methylacrylamide (NAT), methylcellulose acrylate (MCA) represented by the formula: wherein R6 is hydrogen, methyl or vinylcarbonyl and x is an integer of 1 or more, 2-aminoethyl methacrylate hydrochloride (AEM-HCl), allylamine hydrochloride (AL-Am-HCl), dimethylacrylamide (DMAA), acrylic acid (AA), (acryloylamino) (hydroxy) acetic acid (AHA), 4- acryloylmorpholine (AM), 2-(acryloylamino)-2-methyl-1-propanesulfonic acid (AMP), 3-(acryloylamino)phenylboronic acid (APB), [ [3- (acryloylamino) propyl] (dimethyl) ammonio] acetate (APDAA), 3- [ [3- (acryloylamino) propyl] (dimethyl) ammonio]-1-propanesulfonate (APDAP), calcium diacrylate (CDA), 5-chloro-8-quinolinyl acrylate (CQA), 2-{[(2, 4- dioxo-3,4-dihydro-1 (2H)-pyrimidinyl) carbonyl] amino} ethyl 2- methylacrylate (DCAEM), 2-{[(5-fluoro-2, 4-dioxo-3,4-dihydro-1 (2H)- pyrimidinyl) carbonyl] amino} ethyl 2-methylaceylate (FCAEM), 2- (glycosyloxyl) ethyl 2-methacrylate (GEMA), N- (hydroxymethyl) acrylamide (HA), 2- { [ (8-hydroxy-5- quinolinyl) carbonyl] amino}-ethyl 2-methylacrylate (HCAEM), 2- hydroxy-3- (methacryloyloxy)-N, N, N-trimethyl-1-propanaminium chloride (HMTP-HCl), 2-[({[2-(lH-imidazol-5- yl) ethyl] amino} carbonyl) amino] ethyl 2-methylacrylate (IMA), lithium

acrylate (LA), 2-methylacrylic acid (MAA), methyl 2-methylacrylate (MMA), 3,6,9,12,15,18,21,24,27-nonaoxaoctacos-1-yl 2-methylacrylate (NM), 2- { [ (2-oxo-1, 2-dihydro-4-pyrimidinyl) carbonyl] amino} ethyl 2- methylacrylate (OCAEM), trimethyl (vinyl) silane (TVS) and 2-(2-vinyl-1- pyridiniumyl) ethanesulfonate (VPES).

In the above and subsequent descriptions of the present specification and claims, suitable example of"an integer of 1 or more" may be an integer of 1 to 20,000, in which the preferred one is an integer of 1 to 1,000, and more preferred one is 1 to 500, and the most preferred one is 1 to 100.

The preferred radical initiators are the ones having azo group in the molecule and the peroxides which may have perfluoroalkanoyl groups.

The peroxides having perfluoroalkanoyl groups are represented by the formula (III): (R5COO)2 (III) wherein R5 is a perfluor (lower) alkyl group which may have one or more suitable substituent (s) or a cycloalkyl group substituted with one or more of fluorine atom (s).

The preferred radical initiators of the formula (III) are 2,3,3,3- tetrafluoro-2- (1, 1, 2,2,3,3,3-heptafluoropropoxy) propanoyl peroxide (PFPO-2),2,3,3,3-tetrafluoro-2-[1, 1,2,3,3,3-hexafluoro-2- (1,1,2,2,3,3,3- heptafluoropropoxy) propoxy] propanoyl peroxide (PFPO-3), trifluoroacetyl peroxide (FAP), 2,2,3,3,4,4,4-heptafluorobutanoyl peroxide (FBP), 2,3,3,3-tetrafluoro-2- {1,1,2,3,3,3-hexafluoro-2- [1, 1, 2,3,3,3-hexafluoro-2- (1,1,2,2,3,3,3- heptafluoropropoxy) propoxy] propoxy} propanoyl peroxide (PFPO-4), 2,4,4,5,7,7,8,10,10,11,13,13,14,14,15,15,15-heptadecafluoro- 2,5,8,11- tetrakis (trifluoromethyl)-3, 6,9,12-tetraoxapentadecan-1-oyl peroxide (PFPO-5), 1,2,2,3,3,4,4,5,5,6,6-undecafluorocyclohexanecarbonyl peroxide (CPFP) and 1, 2,2,3,3,4,4,4a, 5,5,6,6,7,7,8,8,8a-

heptadecafluorodecahydro-1-naphthalenecarbonyl peroxide (DPFP).

The polymers or their salts obtained by using the peroxides of the formula (III) as a radical initiator may be represented by the formula (IV): wherein R1 and R3 are as defined in the above, and R2 and R4 are as defined in the above, and R2 and/or R4 may be intramolecularly and/or intermolecularly crosslinked with another R2 or R4, Rs is as defined in the above, and n is an integer of 1 or more, and m is an integer of 0,1 or more.

The preferred polymers of the formula (IV) are those wherein Rl, R3, R5, n and m are each as defined in the above, and R2 and R4 are each lower alkyl carbamoyl group or lower alkoxycarbonyl group, each of which may have one or more suitable substituent (s), amino lower alkyl group or carboxy group which may be esterified by the residue of cellulose optionally. substituted with one or more lower alkyl and/or lower alkenoyl, and R2 and/or R4 may be intramolecularly and/or intermolecularly crosslinked with another R2 or R4.

The more preferred polymers (IV) are those wherein Ri, R3, R5, n and m are each as defined in the above, and R2 and R4 are each lower alkyl carbamoyl group which may have one or more hydroxy, lower alkoxycarbonyl group substituted with amino or glycosyloxy, amino lower alkyl group or carboxy group esterified by esterified and/or etherified cellulose, and R2 and/or R4 may be intramolecularly and/or intermolecularly crosslinked with another R2 or R4.

The polymers of the formula (IV) can be obtained by

polymerization of GEMA with AEM-HCl in the presence of PFPO-2 in the molar ratio of GEMA: AEM-HC1 being 1: 2,1: 1,1: 0.5,1: 5 or 1: 20, polymerization of GEMA with AL-Am-HCl in the presence of PFPO-2 in the molar ratio of GEMA: AL-Am-HCl being 1: 0.5, polymerization of NAT with AEM-HC1 in the presence of PFPO-2 in the molar ratio of NAT : AEM-HCl being 1: 0.5, polymerization of MCA in the presence of PFPO-2, polymerization of MCA with AEM-HCl in the presence of PFPO-2 in the molar ratio of MCA : AEM-HCl being 1: 0.6 or 1: 3, polymerization of MCA with AEM-HC1 in the presence of PFPO-3 in the molar ratio of MCA : AEM-HCl being 1: 3 or 1: 4, polymerization of MCA with DMAA in the presence of PFPO-2 in the molar ratio of MCA : DMAA being 1: 2.6 or 1: 5.2, polymerization of MCA with DMAA in the presence of PFPO-3 in the molar ratio of MCA: DMAA being 1: 10.83, polymerization of MCA with AL-Am-HCl in the presence of PFPO-2 in the molar ratio of MCA : AL-Am-HCl being 1: 1.88 or 1: 3, or polymerization of MCA with AL-Am-HCl in the presence of PFPO-3 in the molar ratio of MCA : AL-Am-HCl being 1: 4.

The examples of the radical initiators having azo group or peroxides are 2,2'-azobis (2-amidinopropane) dihydrochloride (V-50), 2,2'-diamidinyl-2,2'-azobutane dihydrochloride, 2,2'-diamidinyl-2,2'- azopentane dihydrochloride, 2,2'-bis (N-phenylamidinyl)-2,2'- azopropane dihydrochloride, 2,2'-bis (N-phenylamidinyl)-2,2'-azobutane dihydrochloride, 2,2'-bis (N, N-dimethylamidinyl)-2, 2'-azopropane dihydrochloride, 2,2'-bis (N, N-dimethylamidinyl)-2, 2'-azobutane dihydrochloride, 2,2'-bis (N, N-diethylamidinyl)-2, 2'-azopropane dihydrochloride, 2,2'-bis (N, N-diethylamidinyl)-2, 2'-azobutane dihydrochloride, 2,2'-bis (N, N-di-n-butylamidinyl)-2,2'-azopropane dihydrochloride, 2,2'-bis (N, N-di-n-butylamidinyl)-2,2'-azobutane dihydrochloride, 3,3'-bis (N, N-di-n-butylamidinyl)-3,3'-azopentane dihydrochloride, azo-bis-N, N'-dimethyleneisobutylamidine dihydrochloride, 2,2'-azobis (2,4-dimethyl-4-methoxyvaleronitrile (V-70), 2,2'-azobis (2-methylpropionitrile) (AIBN), benzoylperoxide (BPO) and m-

chloroperbenzoic acid (MCPBA).

The commercially available VA-545, VA-546, VA-548, VA-041, VA-044 and VA-046B therefor can be purchased from Wako Pure Chemical Industries Ltd. as radical initiators having azo group.

The preferred polymer or its salt of the invention is the one obtainable by polymerization of a monomer of the formula (I) or its salt in the presence of a radical initiator, Rl is hydrogen atom or lower alkyl group, R2 is lower alkyl carbamoyl group optionally substituted with one or more substituents selected from the group consisting of hydroxy, carboxy, sulfo, N, N-di (lower) alkyl-N- sulfonato (lower) alkylammonio and N, N-di (lower) alkyl-N- carboxylato (lower) alkylammonio ; aryl group optionally substituted with dihydroxyboranyl; lower alkoxy carbonyl group substituted with one or more substituents selected from hydroxy, ammonio and tri (lower) alkylammonio ; carboxy group esterified by the residue of cellulose optionally substituted with one or more lower alkyl and/or lower alkenoyl; or pyridinium group substituted with sulfonato (lower) alkyl, or by polymerization of a monomer of the formula (Ia) or its salt with a monomer of the formula (II) or its salt in a molar ratio of (Ia) : (II) being 1: 0.1 to 1: 25 in the presence of a radical initiator wherein Rla is hydrogen atom or lower alkyl group, R2a is lower alkyl carbamoyl group; lower alkoxy carbonyl group substituted with optionally

substituted-heterocycliccarboamido, heterocyclic (lower) alkylureido or glycosyloxy ; or heterocyclicoxycarbonyl group optionally substituted with halogen or hydroxy; R3 is hydrogen atom or lower alkyl group, R4 is lower alkyl carbamoyl group optionally substituted with sulfonato; carboxy group; lower alkoxycarbonyl group optionally substituted with lower alkoxy in which the alkyl moiety may be interrupted by oxygen atom (s); carboxy group esterified by the residue of cellulose optionally substituted with one or more lower alkyl and/or lower alkenoyl; amino (lower) alkyl group; heterocyclic carbonyl group; or tri (lower) alkylsilyl group, provided that when R2a and R4 are the same, then Rla and R3 are different from each other.

The polymerization is usually carried out in an organic solvent such as 1 ; 1,-dichloro-2, 2,3,3,3-pentafluoropropane, 1,3-dichloro- 1,2,2,3,3-pentafluoropropane or any other organic solvent which does not adversely affect the reaction, or a mixture thereof or a heterogeneous mixed solvent thereof with water.

The reaction is usually carried out in the presence of a radical initiator at a temperature under cooling to warming, preferably at the temperature of 40°C to 50°C.

The polymer or its salt of the present invention can be intramolecularly and/or intermolecularly crosslinked by a suitable crosslinking agent or without a crosslinking agent. An example of the partial structure of the crosslinked polymer is represented by the formula:

wherein R6 and x are each as defined in the above.

The reaction condition can be referred to the Examples mentioned below.

The polymer prepared by the above process can be isolated and purified by a conventional method such as washing with an organic solvent, pulverization, recrystallization, chromatography, reprecipitation or the like.

It is to be noted that the polymer of this invention may include one or more stereoisomer (s) and geometrical isomer (s) due to asymmetric carbon atom (s), and all of such isomer (s) and mixture thereof are included within the scope of this invention.

It is further to be noted that isomerization or rearrangement of the polymers may occur by the effect of light, acid, base or the like, and the compounds obtained as the result of said isomerization or rearrangement are also included within the scope of the present invention.

A pharmaceutically acceptable salt of the polymer can be prepared, for example, by treating the polymer having amino group with

an appropriate acid or by treating the polymer having carboxy group with an appropriate base in accordance with a conventional method.

Also included in the scope of invention are radiolabelled derivatives of the polymer which are useful for biological studies.

The polymers. and pharmaceutically acceptable salts thereof possess ability for adsorbing phosphate.

Therefore, the polymers and pharmaceutically acceptable salts thereof are useful for the treatment and/or prevention of various, diseases caused by accumulated phosphates such as hyperphosphoremia.

In order to exhibit the usefulness of the present invention, the activities of the polymers are shown in the following.

In vitro phosphate binding studies The phosphate solution (20mM Tris, lOmM Phosphoric acid) was adjusted to pH 7.0 with acetic acid. Test polymer (25mg) and the phosphate solution (20ml) were mixed, and then the mixture was shaken vigorously for an hour. Resultant solution was centrifuged for 15 minutes (15,000 rpm) with Microcon Centrifugal filter device (MILLIPORE YM-10). The phosphate concentration of the filtered solution was determined spectrophotometrically by using a standard molybdate assay (Wako P-test). The phosphate binding (%) was calculated by the formula: <BR> <BR> <BR> <BR> <BR> <BR> phosphate binding (%) = Cini-Cbin 100<BR> <BR> <BR> Cini Cini: initial concentration of the phosphate before binding, Cbin: concentration of the phosphate after binding.

Test Results The obtained results are shown in Table 1.

Table 1 Polymer obtained in phosphate binding (%) Example 4 >20 5 >20 8 >20 9 >20 10 >20 13 >20 14 >2. 0 15 >20

As shown in the above Table 1, the polymers of the present invention have superior ability for binding phosphate which indicates that they have superior ability for adsorbing phosphate.

The polymer and its salt can be administered alone or in a form of a mixture, preferably, with a calcium compound such as calcium chloride, calcium carbonate and the like. A pharmaceutical composition comprising a polymer or its salt as an active ingredient in association with a calcium compound is preferred in view point of the phosphate binding ability.

The active ingredient of this invention can be used in a form of a pharmaceutical preparation, for example, in solid or semisolid form, which contains a polymer as an active ingredient in admixture with a pharmaceutically acceptable, substantially non-toxic organic or inorganic carrier or excipient suitable for oral, parenteral such as intravenous, intramuscular, subcutaneous, intracavemous or intraarticular, external such as topical, intrarectal, transvaginal, inhalant, ophthalmic, nasal or hypoglossal applications. The active ingredient may be compounded, for example, with the conventional non-toxic, pharmaceutically acceptable carriers or excipients for ointment, cream, plaster, tablets, pellets, capsules, suppositories, emulsion, suspension, aerosols, pills, powders, syrups, injections,

troches, cataplasms, buccal tablets, sublingual tablets or any other form suitable for use.

The carriers which can be used are olive oil, wax, glucose, lactose, gum acacia, gelatin, mannitol, starch paster, magnesium trisilicate, talc, corn starch, keratin, paraffin, colloidal silica, potato starch, urea and other carriers suitable for use in manufacturing the above-mentioned preparations. In addition, auxiliary, stabilizing, thickening or coloring agents and perfumes may be used. The active polymer is included in a pharmaceutical composition in an effective amount sufficient to show the desired effect.

While the therapeutically effective amount of a polymer varies depending upon the age and condition of each individual patient to be treated, in case of the systemic administration, a daily dose of about 0.01 mg-100 g, preferably 0.1 mg-50 g and more preferably 0.5 mg-10 g of the active ingredient is generally given for treating the diseases, and an average single dose of about 0.2-0.5 mg, 1 nig, 5 mg, 10 mg, 50 mg, 1 g, 2.5 g and 5.0 g is generally administered. Daily doses for chronic administration in humans is in the range of about 0.3 mg/body to 50 g/body.

BEST MODE FOR CARRYING OUT THE INVENTION The following Examples are given only for the purpose of illustrating the present invention in more detail.

Example 1 2,3,3,3-tetrafluoro-2-[1, 1,2,3,3,3-hexafluoro-2- (1,1,2,2,3,3,3- heptafluoropropoxy) propoxy] propanoyl peroxide (PFPO-3,2mmol) in : 1 mixed solvents of 1, 1-dichloro-2, 2,3,3,3-pentafluoropropane and 1,3- dichloro-1, 2,2,3,3-pentafluoropropane (200 g) was added to an aqueous solution (4.50 g) of 2-glucosylethyl methacrylate (GEMA: 6 mmol) and 2-aminoethyl methacrylate hydrochloride (AEM-HC1 : 12 mmol). The heterogeneous solution was stirred vigorously at 45°C for 5 hours under nitrogen. The obtained crude product was washed well with methanol to remove the unreacted GEMA and AEM-HC1, and dried over in vacuo at

50°C to give a polymer hydrochloride (2.63 g).

IR (KBr) : 3450 (OH), 3100 (NH3+) ; 1720 (C=O), 1639 (NH3+), 1330 (CF3), 1243 (CF2) cm-1.

This polymer causes gelation with water and DMSO (dimethylsulfoxide). The gelation ability of this polymer was studied by measuring critical gel concentration (CGC, g/L) of this polymer in water or DMSO. CGC in water and DMSO are 123 g/L and 173 g/L, respectively.

Example 2 2,3,3,3-tetrafluoro-2-(1, 1,2,2,3,3,3- heptafluoropropoxy) propanoyl peroxide (PFPO-2,1.9 mmol) in 1: 1 mixed solvents of 1, l-dichloro-2, 2,3,3,3-pentafluoropropane and 1,3- dichloro-1, 2,2,3,3-pentafluoropropane (17.71 g) was added to a mixture of a solution of AEM-HC1 (0.95 g, 5.7 mmol) in water (9.0 g) and 3.31 g (5.7 mmol) of 50% aqueous solution of GEMA. After adding 100 g of the 1: 1 mixed solvents of 1, 1-dichloro-2, 2,3,3,3-pentafluoropropane and 1, 3-dichloro-1, 2,2,3,3-pentafluoropropane, the mixture was stirred vigorously with a mechanical stirrer at 45°C for 5 hours under nitrogen.

The crude product was isolated and washed well with methanol to remove the unreacted GEMA and AEM-HC1, and dried. over in vacuo at 50°C for 2 days to give a polymer hydrochloride (2.68 g).

IR (KBr) : 3450 (NH3+, OH), 1724, 1635 (C=O), 1300 (CF3), 1244 (CF2) cm-1.

CGC in water and DMSO are 267 g/L and 115 g/L, respectively.

The obtained polymer causes gelation only with water and DMSO. This polymer was insoluble in methanol, ethanol, tetrahydrofuran, chloroform, benzene, toluene, ethyl acetate, 1: 1 mixed solvents of 1, 1-dichloro-2, 2,3,3,3-pentafluoropropane and 1,3-dichloro- 1,2,2,3,3-pentafluoropropane, dimethylformamide, n-hexane, acetone or dichloromethane.

Examples 3 to 7 Each polymer was prepared from monomers and a radical initiator in a similar manner to Example 1. The kinds and molar ratio of the monomers and the radical initiator used in each Example are shown in Table 2.

Table 2 Example monomer molar ratjio monomer molar ratio radical molar ratio CGC (g/L) in H2O in DMSO in DMF 1 GEMA 6 AEM-HCl 12 PFPO-3 2 123 173 n.d. 2 GEMA 6 AEM-HCl 6 PFPO-2 2 267 115 n.d. 3 GEMA 12 AEM-HCl 6 PFPO-2 2 130 49 n.d. 4 GEMA 6.4 AEM-HCl 32 PFPO-2 3.2 n.d. n.d. n.d. 5 GEMA 1 AEM-HCl 20 PFPO-3 2 n.d. n.d. n.d. 6 GEMA 12 AL-Am-HCl 6 PFPO-2 2 131 90 128 7 NAT 12 AEM-HCl 6 PFPO-2 2 33 32 n.d. n.d. :not determined,<BR> PFPO-2 : 2,3,3,3-tetrafluoro-2-(1,1,2,2,3,3,3-heptafluoropropoxy)prop anoyl peroxide;<BR> PFPO-3: 2,3,3,3-tetrafluoro-2[1,1,2,3,3,3-hexafluoro-2-(1,1,2,2,3,3, 3-heptafluoropropoxy)propoxy]propanoyl peroxide;<BR> GEMA : 2-glycosyoxylethyl methacrylate AEM-HCl: 2-aminoethyl methacrylate hydrochloride ; AL-Am-HCl: allylamine<BR> hydrochloroide; NAT; N-tris[hydroxymethylmethylacrylamide; CGC; critical gel concentratjion

The IR spectrum of the polymers obtained in Examples 3 to 7 are shown in Table 3.

Table 3 Example IR (KBr) cm-1 3 3442 (OH), 3224 (NH3+), 1710,1639 (C=O), 1310 (CF3), 1245 (CF2). 4 3444 (OH), 3160 (NH3+), 1727,1623 (C=O), 1320 (CF3), 1245 (CF2). '53473 (OH), 3160 (NH3+)m, 1720,1624 (C=O), 1315 (CF3), 1246 (CF2). 6 3442 (OH), 3205 (NH3+), 1715,1639 (C=O), 1340 (CF3), 1245 (CF2). 7 3450 (OH), 3147 (NH3+), 1728,1649 (C=O), 1639 (NH3+), 1315 (CF3).

Example 8 , 2,3,3,3-tetrafluoro-2- (1,1,2,2,3,3,3- heptafluoropropoxy) propanoyl peroxide (PFPO-2, 2.6 mmol) in 1 : 1 mixed solvents of 1, l-dichloro-2, 2, 3,3,3-pentafluoropropane and 1,3- dichloro-1,2,2,3,3-pentafluoropropane (150 g) was added to an aqueous solution (100 g) of methylcellulose acrylate (MCA: 1.00 g; Monomer- Polymer & Dajac Labs., Inc.) and 2-aminoethyl methacrylate hydrochloride (AEM-HC1 : 2.9 mmol). The heterogeneous solution was stirred vigorously at 45 °C for 5 hours under nitrogen atmosphere.

Methanol was added to the reaction mixture, and the solvent was evaporated. The crude product was reprecipitated from a mixture of methanol and ethyl acetate to give a polymer hydrochloride (0.90 g). IR (KBr): 3463 (OH), 1728 (C=O), 1641 (NH3+), 1389 (CF3), 1271 (CF2) cm-1.

This polymer causes gelation with water, chloroform, DMSO and DMF. The critical gel concentration (CGC) of this polymer in water is 107 g/L.

Examples 9 to 19 Each polymer was prepared from monomers and a radical initiator in a similar manner to Example 8. The kinds and molar ratio of the monomers and the radical initiator used in each Example are shown in Table 4.

Table 4 Example monomer molar ratio monomer molar ratjio radical molar ratjio CGC (g/L) initiator in H2O in DMSO in DMF 8 MCA 5 AEM-HCl 3 PFPO-2 3 107 n.d. n.d. 9 MCA 5 AEM-HCl - - PFPO-2 1 251 122 116 10 MCA 5 AEM-HCl 15 PFPO-2 3 n.d. n.d. n.d. 11 MCA 5 AEM-HCl 15 PFPO-2 3 n.d. n.d. n.d. 12 MCA 5 AEM-HCl 20 PFPO-2 3 n.d. n.d. n.d. 13 MCA 5 DMAA 13 PFPO-2 1 114 89 81 14 MCA 5 DMAA 13 PFPO-2 3 72 n.d n.d. 15 MCA 2.5 DMAA 13 PFPO-2 3 56 n.d. n.d. 16 MCA 1.2 DMAA 13 PFPO-3 3 68 n.d. n.d. 17 MCA 4.9 AL-AM-HCl 2.6 PFPO-2 2.6 162 n.d. n.d. 18 MCA 5 Al-Am-HCl 15 PFPO-3 3 n.d. n.d. n.d. 19 MCA 5 Al-Am-HCl 20 PFPO-3 3 n.d. n.d. n.d. n.d. :not determined,<BR> PFPO-2 : 2,3,3,3-tetrafluoro-2(1,1,2,2,3,3,3-heptafluoropropoxy)propa noyl peroxide;<BR> PFPO-3: 2,3,3,3-tetrafluoro-2-[1,1,2,3,3,3-hexafluoro-2-(1,1,2,2,3,3 m,3-heptafluoropropoxy)propoxy]propanoyl peroxider;<BR> MCA: methylcellulose acrylate; AEM-HCl: 2-aminoethyl methacr ylate hydrochloride: DMAA: dimethylacrylamide;<BR> AL-Am-HCl : allylamine hydrochloride; CGC; critical gel concentration

The IR spectrum of the polymers obtained in Examples 10 to 12, 14 and 17 to 19 are shown in Table 5.

Table 5 Example IR (KBr) cm-1 10 3437 (OH), 1724,1620 (C=0), 1310 (CF3), 1240 (CF2). 11 3453 (OH), 1725,1626 (C=0), 1320 (CF3), 1244 (CF2). 12 3505 (OH), 3116 (NH3+), 1724,1628 (C=O), 1310 (CF3), 1261 (CF2). 14 3461 (OH), 1635 (C=0), 1334 (CF3), 1228 (CF2). 17 3469 (OH), 1637 (C=0), 1322 (CFs), 1240(CF2), 18 3457 (OH), 1638 (C=0), 1321 (CF3), 1240 (CF2). 19 3440 (OH), 1635 (C=0), 1315 (CF3), 1249 (CF2).

Example 20 A 50% aqueous solution of GEMA (5.85 g, 10 mmol) was added to a solution of AEM-HCl (1. 66 g, 10 mmol) and 2,2'-azobis (2- amidinopropane) dihydrochloride (V-50,0.542 g) in water (16.56 g).

After adding 100 g of the 1 : 1 mixed solvents of 1, 1-dichloro-2, 2,3,3,3- pentafluoropropane and 1, 3-dichloro-1, 2,2,3,3-pentafluoropropane, the mixture was stirred vigorously with a mechanical stirrer at 50°C for 10 hours under nitrogen atomosphere. The obtained crude product was washed well with methanol to remove the unreacted GEMA and AEM- HC1, and dried in vacuo at 50°C for 2 days to give a polymer hydrochloride (4.37 g).

IR (KBr): 3440 (NH3+, OH), 1718,1635 (C=O) cm-1, CGC in water and DMSO are 44 g/L and 19 g/L, respectively.

The obtained polymer causes gelation only with water and DMSO. This polymer was insoluble in methanol, ethanol, tetrahydrofuran, chloroform, benzene, toluene, ethyl acetate, 1: 1 mixed solvents of 1, l-dichloro-2, 2,3,3,3-pentafluoropropane and 1,3-dichloro- 1,2,2,3,3-pentafluoropropane, dimethylformamide, n-hexane, acetone or dichloromethane.

Examples 21-158 Each polymer was prepared from monomers and a radical initiator in a similar manner to Example 20. The kinds and molar ratio of the monomers and the radical initiator used in each Example are shown in Table 6.

Table 6 Example monomer molar monomer molar radical molar No. ratio ratio initiator ratio 21 APDAP 13.1 - - FBP 4. 4 22 APDAP 10. 03--PFPO-2 3. 3 23 APDAP 8. 4--PFPO-4 0. 8 24 APDAP 10. 1--PFPO-2 0. 5 25 APDAP 2. 95--PFPO-4 0. 98 26 APDAP 6.16 - - PFPO-3 0. 62 27 APDAP 11. 1--V-50 1. 11 28 VPES 7.3 - - PFPO-2 2. 6 29 VPES 5.9 MMA 6.3 PFPO-3 1. 4 30 APDAA 6--V-50 2 31 APDAA 10. 1--FBP 3. 4 32 APDAA 30. 4--FBP 3. 4 33 APDAA 33.1 - - FBP 3. 3 34 APDAA 66. 3--FBP 3. 3 35 APDAA 4.1 - - PFPO-4 1.4 36 APDAA 8.9 - - PFPO-4 O. 89 37 APDAA 17. 86 PFPO-4 0. 89 38 APDAA 16.6 - - PFPO-3 1. 66 39 APDAA 33.1 - - PFPO-3 1. 66 40 APDAA 4.29 - - FBP 2. 86 41 APDAA 57.3 - - FBP 2. 86 42 APDAA 39.0 - - FBP 3. 9 43 APDAA 4.53 - - PFPO-5 0. 45 44 APDAA 9.06 - - PFPO-5 0. 45 45 AEM-HCl 5 - - PFPO-2 1 Example monomer molar monomer molar radical molar No. ratio ratio initiator ratio 46 AEM-HCl 5 - - CPFP 1 47 AEM-HCl 5 - - FBP 1 48 AEM-HCl 5 - - PFPO-4 1 49 AEM-HCl 5 - - PFPO-3 1 50 AEM-HCl 60 - - CPFP 4 51 VPES 17. 51 MMA 18. 65 PFPO-2 4. 2 52 AEM-HCl 8.3 AMP 24.8 PFPO-2 8. 3 53 GEMA 24. 9 NM 12. 4 PFPO-2 5 54 GEMA 12.1 NM 6.0 PFPO-3 2. 4 55 GEMA 25 MAA 25 PFPO-2 5 56 GEMA 20 MAA 20 PFPO-3 4 57 HMTP-HCl 25.1 - - PFPO-2 5. 0 58 HMTP-HCl 85.86 - - PFPO-2 4. 29 59 HMTP-HC1 64. 4 PFPO-2 4. 29 60 HMTP-HCl 42.2 - - PFPO-2 4. 2 61 HMTP-HCl 16.59 - - V-50 3. 3 62 HMTP-HCl 26.87 TVS 8.44 PFPO-2 4. 2 63 AHA 41.2 - - FBP 4. 1 64 AHA 25. 1--PFPO-2 5. 0 65 AHA 50. 2--PFPO-2 5. 0 66 AHA 26. 45--PFPO-3 2. 6 67 NAT 5. 3--PFPO-2 5 68 NAT 28. 5--V-50 2. 9 69 NAT 5.3 - - PFPO-3 2. 6 70 NAT 8--FBP 4 71 NAT 13 MMA 13 PFPO-3 2. 7 72 NAT 21 TVS 21 PFPO-2 4. 7 73 NAT 21 TVS 21 FBP 4. 4 74 NAT 13 - - PFPO-3 2 6 75 HMTP-HCl 4.65 - - DPF P 0. 31 76 IMA 7 DMAA 93 PFPO-2 1 Example monomer molar monomer molar radical molar No. ratio ratio initiator ratio 77 IMA 7 DMAA 93 PFPO-3 1 78 IMA 13 DMAA 87 V-50 1 . 79 CQA 11. 18 AA 11. 18 PFPO-2 3. 73 80 CQA 4. 28 AA 12. 8 PFPO-3 2. 14 81 CQA 36. 4 DMAA 36. 4 PFPO-2 3. 64 82 FCAEM 93 DMAA 7 PFPO-2 1 83 FCAEM 7 DMAA 93 PFPO-3 1 84 FCAEM 10 DMAA 90 PFPO-4 1 85 FCAEM 13 DMAA 87 V-50 1 86 HCAEM 1 AM 10 PFPO-3 1 87 HCAEM 2 AM 10 V-50 0. 5 88 HCAEM 1 DMAA 10 PFPO-3 1 89 HCAEM 2 DMAA 10 V-50 0. 5 90 APB 2.1 - - PFPO-2 0. 7 91 APB 0. 78 DMAA 3. 9 PFPO-2 0. 78 92 MCA 5-V-50 1 93 MCA 4. 9 DMAA 13 V-50 0. 37 94 GEMA 5 AEM-HC1 5 V-50 1 95 GEMA 6 AEM-HC1 3 PFPO-2 1 96 GEMA 2 AL-Am-HCl 1 PFPO-2 2. 4 97 GEMA 13 LA 13 PFPO-2 3 98 AL-Am-HCl CDA 28 PFPO-2 99 - - CDA 28 PFPO-2 9 100 - - CADA 30.12 V-50 2. 6 101 GEMA 13 CDA 13 PFPO-2 3 102 GEMA 21 AL-Am-HCl 8 PFPO-2 4 103 AM 9 CDA 3 PFPO-2 9 104 NM 14 CDA 14 PFPO-2 3 105 GEMA 6 AL-Am-HCl 20 V-50 3. 69 106 GEMA 4 AEM-HCl 20 V-50 3. 69 107GEMA1AEM-HC110V-501. 84 Example, monomer molar monomer molar radical molar No. ratio ratio initiator ratio 108GEMA0. 5AEM-HC110V-501. 84 109 MCA 1 AME-HCl 15 V-50 41 110 MCA 2.5 AEM-HCl 15 V-50 0. 37 111 MCA 5 AEM-HCl 15 V-50 0. 41 112 MCA 7. 5 AEM-HC1 15 V-50 0. 37 113 MCA 5 AEM-HCl 15 PFPO-2 3 114 MCA 5 AEM-HC1 15 PFPO-3 3 115 MCA 5 AEM-HCl 20 PFPO-3 3 116 MCA 5 AL-Am-HCl 15 V-50 0 41 117 MCA 5 AL-Am-HCl 20 V-50 0 41 118 HMT P-HCl 44.2 GEMA 21.6 PFPO-2 2. 2 119 HMT P-HCl 5 AEM-HCl 20 PFPO-2 2. 2 120 NAT 00 HMTP-HCl 20 PFPO-2 2. 2 121NAT2AEM-HC110PFPO-21 122NAT1AEM-HC110PFPO-21 123NAT2AEM-HC116PFPO-21 124 NAT 1 AEM-HCl 16 PFPO-2 1. 125NAT3AEM-HC116PFPO-21 126 HA 3.02 AEM-HCl 26.4 PFPO-2 1. 5 127 HA 1.5 AEM-HCl 26.8 PFPO-2 1. 6 128 HA 1.5 AEM-HCl 26.8 PFPO-2 1. 6 129 GEMA 6 AEM-HC1 6 PFPO-2 2 130 GEMA 12 AEM-HC1 6 PFPO-2 2 131 GEMA 6 AEM-HC1 12 PFPO-3 2 132 GEMA 12 AEM-HC1 6 PFPO-2 2 133 GEMA 12 AEM-HC1 6 PFPO-2 2 134 GEMA 12 AEM-HC1 6 PFPO-2 2 135 GEMA 6.4 AEM-HCl 32 PFPO-2 3. 2 136 NAT 9.6 AEM-HCl 19.2 PFPO-2 3. 2 137 NAT 9.6 AEM-HCl 19.2 PFPO-2 3. 2 138 NAT 9.6 AEM-HCl 19.2 PFPO-2 3. 2 Example monomer molar monomer molar radical molar No. ratio ratio initiator ratio 139 GEMA 1 AEM-HCl 10 V-50 1. 84 140 GEMA 1 AEM-HCl 10 V-50 1.84 141 GEMA 1 AEM-HCl 10 V-50 1.84 142GEMA0. 5AEM-HC110V-501. 84 143 G EMA 0.5 AEM-HCl 10 V-50 1. 84 144 GEMA 0. 5 AEM-HC1 l0 V-50 1. 84 145 GEMA 4 AEM-HC1 20 PFPO-3 2 146 NAT 4.8AEM-HC110PFPO-31.6 147 NAT 4.8 AEM-HCl 10 PFPO-3 1. 6 148 NAT 4.8 AEM-HCl 10 PFPO-3 1. 6 149 MCA 5 DMAA 13 PFPO-2 3 150 MCA 5 DMAA 13 PFPO-2 3 151 MCA 5 DMAA 13 PFPO-2 3 152 MCA 5 AEMK-HCl 15 PFPO-3 3 153 MCA 5 AEMK-HCl 15 PFPO-3 3 154 MCA 5 AEMK-HCl 15 PFPO-3 3 155 MCA 5 AEM-HC1 15 PFPO-3 3 156 MCA 5 AEM-HC1 20 PFPO-3 3 i57 MCA 5 AEM-HC1 20 PFPO-3 3 158 MCA 5 AMP 15 PFPO-3 3

PFPO-2: 2,3,3,3-tetrafluoro-2- (1,1,2,2,3,3,3- heptafluoropropoxy) propanoyl peroxide, PFPO-3: 2,3,3, 3-tetrafluoro-2-[1,1, 2,3,3, 3-hexafluoro-2(1, 1,2,2,3,3,3- heptafluoropropoxy) propoxy] propanoyl peroxide, V-50: 2, 2'-azobis(2-aminopropane)dihydrochloride, FAP:trifluoroacetyl peroxide, FBP: 2,2,3,3,4,4,4-heptafluorobutanoyl peroxide, PFPO-4: 2,3,3,3-tetrafluoro-2-{1, 1,2,3,3,3-hexafluoro-2- [1,1,2,3,3,3- hexafluoro-2- (1, 1,2,2,3,3,3- heptafluoropropoxy) propoxy] propoxy} propanoyl peroxide, PFPO-5 : 2,4,4,5,7,7,8,10,10,11,13,13,14,14,15,15,15-heptadecafluoro-

2,5,8,11-tetrakis (trifluoromethyl)-3,6,9,12-tetraoxapentadecan-l-oyl peroxide, CPFP: 1,2,2,3,3,4,4,5,5,6,6-undecafluorocyclohexanecarbonyl peroxide, DPFP: 1,2,2,3,3,4,4,4a,5,5,6,6,7,7,8,,8a-heptadecafluorodecahydro- 1- naphthalenecarbonyl peroxide, AA: acrylic acid, AEM-HC1 : 2-aminoethyl methacrylate hydrochloride, AHA: (acryloylamino) (hydroxy) acetic acid, AL-Am-HCl : allylamine hydrochloride, AM:4-acryloylmorpholine, AMP: 2-(acryloylamino)-2-methyl-1-propanesulfonic acid, APB: 3- (acryloylamino) phenylboronic acid, APDAA : [ [3- (acryloylamino) propyl] (dimethyl) ammonio] acetate, APDAP: 3- [ [3- (acryloylamino) propyl] (dimethyl) ammonio]-1- propanesulfonate, CDA:calcium diacrylate, CQA: 5-chloro-8-quinolinyl acrylate, DCAEM: 2-{[(2, 4-dioxo-3,4-dihydro-1 (2H)- pyrimidinyl) carbonyl] amino} ethyl 2-methylacrylate, DMAA: N, N-dimethylacrylamide, FCAEM: 2- { [ (5-fluoro-2, 4-dioxo-3,4-dihydro-1 (2H)- pyrimidinyl) carbonyl] amino} ethyl 2-methylaceylate, GEMA: 2- (glycosyloxyl) ethyl 2-methacrylate, HA: N- (hydroxymethyl) acrylamide, HCAEM: 2-{[(8-hydroxy-5-quinolinyl) carbonyl] amino}-ethyl 2- methylacrylate, HMTP-HC1 : 2-hydroxy-3- (methacryloyloxy)-N, N, N-trimethyl-1- propanaminium chloride, IMA: 2-[({[2-(1H-imidazol-5-yl) ethyl] amino} carbonyl) amino] ethyl 2- methylacrylate, LA: lithium acrylate, MAA: 2-methylacrylic acid, MMA : methyl 2-methylacrylate,

MCA: methylcellulose acrylate, NAT: N- [2-hydroxy-1, 1-bis (hydroxymethyl) ethyl] acrylamide, NM: 3,6,9,12,15,18,21,24,27-nonaoxaoctacos-1-yl 2-methylacrylate, OCAEM: 2-{[(2-oxo-1, 2-dihydro-4-pyrimidinyl) carbonyl] amino} ethyl 2- methylacrylate, TVS: trimethyl (vinyl) silane, VPES: 2- (2-vinyl-1-pyridiniumyl) ethanesulfonate Preparation 1 The polymer hydrochloride (200mg) obtained in Example 1 and calcium carbonate (2 lmg) were homogeneously mixed in a mortar. The mixture was put into a test tube to which was added water (0.88 ml) to give a gel. Thus obtained wet gel was dried by using an aspirator and further dried at 50°C in vacuo for one day to give white gel-powder containing calcium carbonate.

Preparations 2 to 7 Each polymer hydrochloride (200mg) obtained in Examples 2,3, 4,5,11 and 14 was treated in a similar manner to Preparation 1 to give white gel-powder containing calcium carbonate.

Preparation 8 A 1% calcium chloride aqueous solution (2.29 ml) was added to the polymer hydrochloride (105 mg) obtained in Example 7 in a test tube to give a gel. Thus obtained gel was dried in a similar manner to Preparation 1 to give white gel-powder containing calcium chloride.

Preparations 9 and 10 Each polymer hydrochloride (105 mg) obtained in Examples 14 and 15 was treated in a similar manner to Preparation 8 to give a white gel-powder containing calcium chloride.

Preparation 1 1 A 2.5 % calcium chloride aqueous solution (2.29 ml) was added

to the polymer hydrochloride (105 mg) obtained in Example 7 to give a gel. Thus obtained gel was dried in a similar manner to Preparation 1 to give white gel-powder containing calcium chloride.

Preparation 12 The polymer hydrochloride (105 mg) obtained in Example 14 was treated in a similar manner to Preparation 11 to give white gel-powder containing calcium chloride.

Preparation 13 A 5 % calcium chloride aqueous solution (2.29 ml) was added to the polymer hydrochloride (105 mg) obtained in Example 7 to give a gel.

Thus obtained gel was dried in a similar manner to Preparation 1 to give white gel-powder containing calcium chloride.

Preparations 14 to 16 Each polymer hydrochloride (105 mg) obtained in Example 11, 12 and 14 was treated in a similar manner to Preparation 13 to give white gel-powder containing calcium chloride.

Preparation 17 A 10 % calcium chloride aqueous solution (2.29 ml) was added to the polymer hydrochloride (105 mg) obtained in Example 14 to give a gel.

Thus obtained gel was dried in a similar manner to Preparation 1 to give white gel powder containing calcium chloride.

The CGC values in water of the gel-powder obtained in some of the above Preparations are shown in the following Table 7.

Table 7 Preparation CGC (g/L) Preparation CGC (g/L) 1 142.06 10 115 2 71. 64 12 233 3 71. 68 14 295 4 227. 61 15 217 5 274.38 16 102 9 256 17 175

Preparations 18-40 Each preparation was obtained from the polymer and a calcium compound in a similar manner to Preparations 1 to 17. The kinds and molar ratio of the polymer and the calcium compound are shown in Table 8.

Table 8 Preparation polymer calcium molar ratio of No. obtained in compound calcium compound Example with respect to the polymer 18 132 CaCl2 1% 19 133 CaCl2 2. 5% 20 134 CaCl2 5% 21 136 CaCl2 1% 22 137 CaCl2 2. 5% 23 138 CaCl2 5% 24 139 CaCl2 1% 25 140 CaCl2 2. 5% 26 141 CaCl2 1. 84% 27 142 CaCl2 1. 84% 28 143 CaCl2 1. 84% 29 144 CaCl2 1. 84% 30 145 CaCo3 2% Preparation polymer calcium molar ratio of No. obtained in compound calcium compound Example with respect to the polymer 31 146 CaCl2 1% 32 147 CaCl2 2. 5% 33 148 CaCl2 5% 34 150 CaCl2 5% 35 151 CaCl2 10% 36 153 CaCl2 1% 37 154 CaCl2 2.5% 38 155 CaCl2 5% 39 156 CaCl2 2. 5% 40 157 CaCl2 5%