NL7812425A - Renal calculus treatment with sequestrant - comprising (co)polymer of unsatd. carboxylic acid - Google Patents

Abstract

Treatment of renal calculus comprises administering a (co)polymer (I) derived from an olefinically unsatd. mono- or polycarboxylic acid (II). If (I) is water-soluble, it has mol. wt. >10000, and if it forms colloidal aq. solns. it has swelling index >=10 (pref. 10-500). Unit dose compsns. contain 0.1-20 g of (I), opt. in slat form. Pref. (II) include acrylic, (m)ethacrylic, alpha-chloroacrylic, +-cyanoacrylic, crotonic, beta-acryloxypropionic, hydrosorbic, sorbic, alpha-chlorosorbic, cinnamic, beta-styrylacrylic, hydromuconic, itaconic, citraconic, mesaconic, muconic, glutaconic and aconitic acids. (I) dissolve calculi and bond calcium so that it is excreted in faeces rather than urine. They are effective in treatment of urolithiasis in lower doses than phosphates, and are easily dosed since they can be administered in liquid form. Daily dose is pref. 10-400 mg/kg p.o.

Description

N. O, 27.105

Warren-Teed Laboratories, Inc., Columbus, Ohio,

Yer. St.v. America.

Water-soluble and colloidal water-soluble polymers from monomers containing carboxylic acid groups, as well as pharmaceutical preparations.

The present invention relates to pharmaceutical compositions containing water-soluble and colloidal water-soluble carboxylic acid containing polymers and method of preparing such polymers. Biological studies using rats as test animals have shown that the compositions of the present invention are suitable for binding calcium and dissolving kidney stones. Accordingly, the invention relates to a composition suitable for the treatment of kidney stones, which composition comprises a unit dose of from 10 0.1 g to about 20 g of a water-soluble or colloidal water-soluble homopolymer or copolymer or mixtures thereof, prepared from a monomer or monomers selected from the group consisting of ethylenically unsaturated carboxylic acids containing at least one ethylenically unsaturated double bond and at least one carboxyl group, the polymer having a degree of polymerization ranging from about 10 to about 100,000 and a swelling index from about 10 to about 500j as well as its non-toxic, pharmacologically acceptable salts and a method of treating kidney stones, characterized in that an individual in need of such treatment is administered an effective amount of a homopolymer or copolymer or mixtures thereof, prepared from a monomer or mono mers selected from the group consisting of ethylenically unsaturated carboxylic acids, which contain at least one carboxyl group, this homopolymer or copolymer being 78 1 24 2 5 2. > when soluble, has a molecular weight greater than 10,000 and, when colloidal water soluble, has a swelling index greater than 10.

In the United States of North America alone, there are approximately 250,000 new patients each year with all 5 kidney stones. Analysis of these stones shows that 70% of all renal calculi contain calcium. Although there is no unanimously accepted regime for urolithiasis, reduction in urinary calcium excretion is a means of stone prophylaxis.

Highly substituted sodium cellulose phosphate -jq is currently under clinical investigation and appears to be suitable for the treatment of calcium calculi (Pak et al., New England J. Med. 290 (1974) 4). This product also binds intestinal calcium. The increase in faecal calcium with a sequestering therapy is associated with a lower calcium discharge with the urine. In fact, by increasing the fecal calcium load, calcium sequestering agents reduce the calcium load on the kidney.

Although cellulose phosphate is clinically active, the proposed regimen is 15 to 19 g. In contrast, the soluble and swellable carboxylic acid polymers of the present invention have a 5 to 4-fold increase in in vitro capability and will act at much lower dosages.

The present invention is based on the clearly established fact that patients with urolithiasis can be successfully treated with a diet of limited calcium. Usually large amounts of calcium are absorbed in the intestinal tract and excreted through the kidneys. The polymers of the present invention interrupt this process by binding large amounts of calcium, preventing calcium absorption and reducing the calcium load of the urine. 30

The binding and removal of calcium by highly cross-linked, non-swellable carboxylic acid resins is known and has been used to remove calcium from water and blood. In 1968 Burghele et al., (Iologologist, 6 (1968) 234) introduced the use of resins as an agent for renal stone prophylaxis; however, no active resin was found, which will reduce kidney stone formation. In fact, Lurie et al. (investigative Urology, 13.

78 1 24 2 5 3 • t

Ho. 4> (1976))., That the resin Bower 50WX8 was ineffective by binding calcium in the gastrointestinal tract.

The soluble, non-cross-linked polymers and the slightly cross-linked, colloidal, water-soluble polymers (swelling index greater than 10) with carboxylic acid groups of the present invention act as calcium sequestering agents. In addition, soluble polymers offer many advantages from a dosing standpoint, since they can be administered as liquids.

Water-soluble and colloidal water-soluble carboxylic acid polymers also promote phosphate absorption, a desirable object in patients with kidney stones, since a high level of phosphate in the urine increases the solubility of calcium in the urine.

The compositions useful in the present invention are water-soluble and colloidal water-soluble polymers prepared from ethylenically unsaturated carboxylic acids containing at least one activated carbon-carbon double bond and at least one earboxyl group, i.e. say an acid, which contains an ethylenically unsaturated double bond, which polymerizes easily because it is in the α-β position with respect to an earboxyl group -Ó = (4-C00H or as part of a methylene terminal group), so: OHgsC <.

In the α-β acids, the immediate proximity of the Highly polar earboxyl group to the double bond carbon atoms has a strong activating effect, making the products having this structure very easily polymerizable. Moreover, the presence of the methylene terminal group in a carboxylic acid-containing monomer makes this type of compound polymerizable much more easily than if the double bond were intermediate in the carbon structure. 30

Ethenically unsaturated acids of this great class include such different products as the acrylic acids, for example acrylic acid, methacrylic acid, ethacrylic acid, α-chloroacrylic acid, α-cyanoacrylic acid and the like, crotonic acid, β-acryloxypropionic acid, hydrosorbic acid, sorbic acid, α-chlororbric acid, cinnamic acid, β-styrylacrylic acid (1-carboxy-4-phenylbutadiene-1.3) -hydromuconic acid, 78 1 24 2 5 ^. 4 'tb itaconic acid, citraconic acid, mesaconic acid, muconic acid, glutaconic acid, aconitic acid and the like.

As used herein, the term "carboxylic acid" includes polycarboxylic acids and anhydrides such as maleic anhydride, whereby the anhydrile group is formed by the removal of

one molecule of water from two carboxylic acid groups present on the same polycarboxylic acid molecule. Anhydrides of the types formed by removing water from two or more molecules of the same or different unsaturated acids, such as acrylic anhydride, are not included due to the strong tendency of IQ

hydrolyze their polymers in water and alkali.

It is usually desirable to use as the carboxylic acid monomer one or more α.β-unsaturated carboxylic acids containing at least one carboxyl group with the ethylenically unsaturated double bond α-β relative to at least one carboxyl group. Examples of α-β unsaturated carboxylic acids of this type include the aforementioned acrylic acids and, in addition, β-methacrylic acid (crotonic acid), α-phenylacrylic acid and others, hydrosorbic acid, α-butyl crotonic acid, angelic acid, cinnamic acid, m-chlorocinnamic acid, p -chloro-cinnamic acid, 2,4-dihydroxy-cinnamic acid and other monoethylenically unsaturated monocarboxylic acids, maleic acid, fumaric acid, hydromuconic acid, glutaconic acid, itaconic acid, citraconic acid, mesaconic acid, tricarboxyethylene, tetracarboxyethylene, and ethylenic unsaturated polycarbonate -acryloxyacrylic acid, β-styrylacrylic acid (4-phenyl-1-carboxybutadiene-1.3) and other polyethenically unsaturated monocarboxylic acids, 3-carboxy-pentadiene- (2.4) -acid-1, 2,4-hexadienedioic acid, muconic acid and other polyenic unsaturated polycarboxylic acids and other acid anhydrides of the general formula 0 to 30 i! l! R-CHgC-O-CCHgE1 wherein E and E 'are selected from the group consisting of hydrogen, alkyl, e.g. alkyl with 1 to 10 carbon atoms, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl , nonyl, decyl and the like, halogen, cyano, hydroxy, lactam and lactone groups, aryl, such as phenyl, tolyl, xylyl and the like, aralkyl 78 1 24 2 5 4. -5 such as benzyl and / or cycloalkyl, for example cyclobutyl, cyclopentyl, cyclohexyl and the like.

The preferred carboxylic acid-containing monomers for use in the present invention are the monoethylenically unsaturated acrylic acids of the general formula {5

CH2 = C-C00H

wherein E represents a substituent selected from the group consisting of hydrogen, halogen, hydroxy, lactone, lactam, cyano, alkyl, monovalent aryl, monovalent aralkyl, monovalent alkaryl and monovalent cycloaliphatic. Examples of acrylic acids of this preferred group are acrylic acid itself, methacrylic acid, ethacrylic acid, chloroacrylic acid, bromoacrylic acid, cyanoacrylic acid, α-phenylacrylic acid, α-benzylacrylic acid, α-cyclohexyl acrylic acid, and the like. α-Halogenoacrylic acids readily hydrolyze to the halogen substituent to form hydroxy and lactone groups. 15

Of this group, acrylic acid itself is most preferred because of its generally low cost, ease of availability, and ability to form excellent polymers. Another particularly preferred carboxyl group-containing monomer is maleic anhydride. 20

When cross-linking agents are used (i.e. the amount of cross-linking agent, which is part of the molecule and is therefore another monomer), they are generally used in an amount of from about 0.01% to about 5% and preferably in an amount of about 0.1 to about 2.0% by weight based on the monomer or monomers used. Cross-linking agents can be used include 1,1,1-trimethylolpropane trimethacrylate, styrene, vinyl crotonate, vinyl acetate, polyallyl sucrose, polyallyl pentaerythritol and the like. 30

The degree of polymerization can be between about 10 and 100,000 and is preferably between about 40 and 3000.

The colloidal water-soluble products of the present invention have a swelling index (SI) which is much greater than that of ion exchange resins (SI for ion exchange resins are 2 or 3) and can be used in 78 1 24 2 5 6 in a range from about 10 to about 1500, but usually in a range from about 100 to about 500. The term "colloxal water-soluble" means that the cross-linked products are not true solutions, but colloidal suspensions. the products will deposit by 5, the majority of the product can be separated by ultracentrifugation.

The compounds are administered in a unit dose of about 0.1 to about 20 g.

The compositions containing the carboxylic acid groups containing polymers or their salts as active ingredients and also the polymers or their salts themselves are agents which can be administered in a wide range of therapeutic doses in conventional carriers. The products can be administered in a wide variety of pharmacologically acceptable carriers, for example, in a flavored aqueous solution divided into three or four doses per day. Conventional formulations contain about 10 to about 20% of the product in a suitable aqueous mixture containing a flavoring, color, thickener and preservative. The liquid dosage form may contain, in addition to water, small amounts of ethanol or one or more other pharmacologically acceptable solvents. Other dosage forms include gels prepared with pectin, agar, hydroxyethyl cellulose or other authorized gelling agents, tablets, capsules, pills, which may be in microcapsule form or coated with gastric acid resistance. Your preparations may contain combinations of drugs, which are especially suitable for treating kidney stones and relieving pain. Other oral drug combinations are also within the scope of the present invention.

The oral daily dosage of the products can be varied over a wide range from about 10 mg to about 4 mg / kg / day. The product can be administered in divided doses in the form of scored tablets or 35 capsules; however, for the soluble polymers, the fluids deserve 78 1 24 2 5 7 ¢.

bare dosage forms are preferred. These dosage forms allow the symptomatic control of the dosage to the patient to be treated. An effective amount of the drug is usually administered at an integrity dose level of from about 10 mg to about 400 mg / kg body weight. At front 5

the range is 20 mg to 150 mg / kg body weight / day. Example I

Tablets containing 500 mg of active ingredient per tablet.

• per tablet polyacrylic acid 10 mol. Weight 400 * 000 500 mg dibasic sodium phosphate 73 mg lactose 70 mg corn starch 50 mg magnesium stearate 7 mg 15

Each component is weighed and passed through a 0.42 mm mesh sieve. The ingredients are mixed in a double cone mixer for 10 minutes. Tablets are compressed up to a weight of 700 mg per tablet on a tableeer maehine. 20

Example II

Oral elixir dosage form, containing 500 mg of active ingredient • per 5 ml.

per 5 ml of polyacrylic acid mol. wt. 400,000 750 mg of sorbitol solution 70 wt. 5 mg PD&C yellow No. 5 0.2 mg flavoring * 0.03 mg 30 purified water qs

Polyacrylic acid is dissolved in an amount of water by gentle stirring. The sorbitol is added to this solution. The PD&C yellow No. 5 is dissolved in an amount of water and added to the aforementioned solution. The 55 propyl paraben is dissolved in an amount of ethanol. The 78 1 24 2 5 7.Φ

a

flavoring agent is dissolved in the remaining amount of ethanol.

The heather ethanolic solutions are then added to the aqueous solution. Sufficient water is then added with continuous stirring to bring to the final volume. 5

Example III

Oral opiose singdo s sation form. containing 500 mg of active ingredient • per 5 ml.

• per 5 ml copolymer of ethylene and maleic anhydride (water soluble) 750 mg propylene glycol 100 mg saccharin sodium 0.05 mg propyl paraben 5 mg flavoring 0.05 mg PD & C yellow No. 0.2 mg 15 purified water qs

The water-soluble copolymer (MA.-31) is dissolved in an amount of water by gentle stirring. The saccharin sodium is dissolved in a small amount of water. The PD&C yellow No. 5 is dissolved in a small amount of water. These two solutions are added to the aforementioned solution. The propyl paraben is dissolved in a small amount of propylene glycol and the flavoring agent is dissolved in the remaining amount of propylene glycol. Both propylene glycol solutions are then added to the aforementioned aqueous solution. Sufficient water is then added with continuous stirring to bring to the final volume.

Example IV

Dry-filled capsules containing 250 mg of active ingredient per 30 capsules.

per capsule polyacrylic acid (example XVl) 250 mg magnesium stearate 2.5 mg 252.5 mg 78 1 24 2 5 8 '** *. ·

The polyacrylic acid and the magnesium stearate are weighed and passed through a 0.42 mm mesh sieve.

The ingredients are mixed in a double cone mixer for ten minutes. Each Ho gelatin capsule. 0 is filled with 252.5 mg of the mixed product. 5

The polymers are known or can be prepared by methods known per se. See, for example, U.S. Pat. Nos. 2,798,055, 3-224-941, 3-842,022, and 3-957-973-Examples V-XV

Polyacrylic acid with a molecular weight of 400,000 10

Into a 5 liter round bottom flask equipped with a stirrer, a thermometer and monomer and catalyst solution addition means, 22 ml of deionized water are charged. Heat is supplied to bring the temperature of the initially added water to 95 ° C. Then an initiating catalyst in an amount of 0.83 g of ammonium persulfate is added. One minute later, a monomer amount of 905 g of anhydrous acrylic acid and a catalyst solution of 1.20 g of ammonium persulfate (APS) in 100 ml of deionized water are gradually added over a period of about 100 minutes. The temperature is kept at 92-96 ° C during the additions. After the additions are complete, the product is held at 90-96 ° C for another 60 minutes. Ha this period is cooled. While cooling, 350 ml of deionized water are added. The final product is a transparent viscous solution with a polymer content of 24%.

By following essentially the procedure of Example V and by varying the amount of catalyst or by using different monomers or mixtures of monomers, other polyacrylic acids, homopolymers or copolymers of the invention can be prepared. A cleaning catalyst is sometimes used and added after the addition of the monomer and catalyst have been completed. The following Table A lists the amount of catalyst used, the cleaning catalyst, the solids, and the viscosity.

78 1 24 2 5 9

TABLE · A

Example catalyst cleaning solids viscosity wt.% Catalyst ___________ VI 0.225 none 24 4 14,600 VII 0.225 none 24.2 10,200 VIII 0.24 0.1 # APS 20.5 4-000 IX 0.57 0, 05 # APS 29.9 7,000 X 0.60 0.1% APS 30.1 5,200 XI 0.65 0.5% APS 29.4 4,100 XII 0.90 0.1% ITaHSO 29.3 2,080 XIII 1.10 0.04 # BHP / 30.0 1,660 0.3% Formopan XIV 1.80 0.1% APS 30.8 540 XV 2.00 0.1% APS 30.4 400 XVa 0.75 none 22.0 800 APS - ammonium persulfate BHP - tert.butyl hydroperoxide

Formopan - sodium sulfoxylate formaldehyde.

Example XVI Polyethyl Acid.

2515 g of deionized water (Bi) are fed to a three-necked flask with a capacity of 12 1, which is provided with a large Teflon stirring blade, gas inlet pipe, heating jacket with a capacity of 12 1, thermometer with a connected Thermowatch sensor and stirring motor. and added 946 g of table salt. The flask and the solution are stirred well for one hour and purged with nitrogen to replace oxygen while the salt dissolves. To the medium stirred solution at ambient temperature, 18.5 g of Primafloc C-7, suspended in 100 g of BI water, are slowly added. When the salt is completely dissolved with Primafloc C-7 completely dispersed, it is mixed with 1.0 g (0.5 mol% acrylic acid) lauroyl peroxide dissolved in 214 µg toluene, 491 g (6.82 mol) acrylic acid and 4.9 g 1.1.1-trimethylolpropane trimethacrylate and the solution is added below the surface of the saline through a long stem funnel. The 78 1 24 2 5 10.

Organic organics / water-containing mixture is stirred at 113 revolutions per minute for 10 minutes, stopped, and stirred int emissively for 30 to 60 seconds until a dispersion is observed (voluminous shiny, bright points visible by illumination with a flickering light, indicates 5 the desired suspension is present). The reaction mixture is gradually heated to 55 ° C. Heating is continued while 26.5% brine solution is added from a dropping funnel (1800 ml brine solution is added). The temperature is then increased in steps of 5 to 10 ° C for periods of 15 to 30 minutes each until 90 ° C is reached.

(Such accuracy is necessary during heat supply to avoid excessive swelling and foaming of the product).

The flaky mixture is heated at 90 ° C for two hours to decompose any remaining lauroyl peroxide. The flask 15 is then refluxed and 950 g of a water / toluene azeotrope are distilled at a temperature of the distillation flask of H 2 ° C. About 600 ml of brine are added during the distillation in amounts of --------- from 100 to 200 ml -, - to control the ratio 'or-gani-sah'product / salt * - * ~ 20 and keep it. The reaction mixture is cooled to ambient temperature. The brine is easily aspirated under reduced pressure through a fine mesh sieve or muslin sieve to yield 3100 ml of filtrate. The system is then transferred to a 12-liter resin kettle equipped with a heavy metal stirrer, necessary to stir the flaky heavy product.

5 * 000 ml Dl water are added and the reaction mixture is stirred for at least 30 minutes. Filtration gives 400 ml of filtrate with a pH of 2.8, Hegen's four washes and filtrations

are performed as previously described and are in Table D.

(The swelling increases with each wash as the salt level is gradually reduced).

78 1 24 2 5 -Λ * 'r 11

TABLE B

washing treatment filtration vE

1 4600 ml 2.8 2 4000 ml 5.2 3 5000 ml 3.5 4 4500 ml 3.5 5 4500 ml 3.8

The aqueous product is then air dried overnight and spread in a thin layer on an aluminum foil. The product is then dried under reduced pressure at 80-90 ° C for 24 hours, whereby 450 g (yield 90.7%) of polyacrylic acid are obtained as a white

brittle solid. Percent EaCl 3.1 found; water found according to KJ 3.1%; vry AA 0.1% (gas-liquid chromatography). Example XVII

Polymethoric Acid (S.I. = 59) One ml of a solution containing 0.0452 g of ethanolamine triacrylate dissolved in anhydrous methacrylic acid (MAA) is combined with enough additional MAA to bring the total weight to 39.86 g. Bit is diluted with 78.0 g of distilled water, transferred to a polyethylene reaction and degassed with nitrogen for 90 minutes. The degassing is added as initiator cumene peroxide (0.1118 g) and isoascorbic acid (0.0102 g) at 1 minute intervals with gentle swirling to mix, the nitrogen atmosphere is made up and the reaction mixture is added in a warm water bath of 35-40 ° C and the contents are periodically mixed by gentle shaking. The solution becomes more viscous and finally reaches a gel capacity in 5 hours. After overnight storage in a 35 ° G water bath to ensure complete polymerization, the gel is removed, cut into pieces and dried in a vacuum oven at 60 ° C for 72 hours before grinding and sieving through a mesh-screen 0.25 mm, whereby 41.5 S of polymethacrylic acid are obtained. The swelling index in deionized water is 59%. Maximum soluble components (24 hours extraction) are 13.6%.

78 1 24 2 5 12 v

Si.

Pharmacological data The action of the products of the present invention is given in Table 0, the test products being present at concentrations of 1% of a normal protein test diet. The test animal is a female rat of the Sprague-hawley type. 5

Eight rats are used per compound to be tested. All faeces excreted on the fourth and fifth days are collected and analyzed for calcium (atomic absorption) and phosphate (Fiske-Subbarow's method).

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From the results it appears that, compared to micro-crystal cellulose (the control test), all the carboxylic acid containing polymers of the present invention and also sodium cellulose phosphate, cause an increase in faecal calcium excretion. All carboxylic acid containing polymers. 5 also a decrease in faecal phosphate excretion compared to both the control test and sodium cellulose phosphate. This inverse relationship between faecal calcium and faecal phosphate is expressed as the calcium / phosphate ratio. The ability of a product to increase faecal calcium excretion and decrease faecal phosphate excretion is highly desirable for the treatment of kidney stones. Essentially, the active product reduces the calcium load on the kidney and increases the amount of phosphate passing through the kidney. The net effect will be to dissolve the calcium-containing stones and / or prevent the formation of calcium deposits in the kidney or urinary tract.

Some theories suggest that an increase in urinary phosphate secretion is even more important than a decrease in urinary calcium as far as the solution of kidney stones is concerned. It has been found that the decrease in faecal phosphate caused by the administration of colloidal water-soluble and water-soluble carboxylic acid containing polymers results in a marked increase in urine phosphate.

The following is an experiment comparing the PQ4 excretion in the urine and the amount of P04 present in the faeces of rats fed cellulose or a swellable polymer of the present invention (ethylene maleic anhydride - EMA-81).

The rats (6 by each trial) were trained to eat every 24 hours for a four hour period. During the remaining 20 hours per day, the rats were placed in metabolism cages so that pure urine could be collected.

After eight days, the rats were sacrificed and the amount of PO4 present in their ceacum and colon (faecal PO4) was determined.

The results in Table D show that EMA-81 caused a threefold increase in PO concentration in the urine with a 4 concomitant decrease in faecal PO4.

78 1 24 2 5

Claims (11)

A homopolymer or copolymer or mixtures thereof prepared from a monomer or monomers selected from the group consisting of ethylenically unsaturated carboxylic acids containing at least one carboxyl group, the homopolymer or copolymer, if soluble, having a molecular weight greater than 10,000, and, if colloidal water-soluble, a swelling index greater than 10. 1. The numbers quoted are mean ± SEM. 2. Homo or copolymer according to claim 1, characterized in that it is prepared from acrylic acid, methacrylic acid, ethacrylic acid, α-chloroacrylic acid, α-cyanoacrylic acid, crotonic acid, β-acryloxypropionic acid, hydrosorbic acid, sorbic acid, α-chlororbic acid, cinnamic acid, β-styrylacrylic acid, hydromuconic acid, itaconic acid, citraconic acid, mesaconic acid, muconic acid, glutaconic acid, aconitic acid, maleic anhydride, anhydrides of the formula 15 0 0 li'il r-ch2-coc-ch2-r where E and R 'are selected from the group consisting of hydrogen, halogen, cyano, hydroxy, lactam and lactone groups, alkyl, aryl, alkaryl, aralkyl and cycloalkyl, with a degree of polymerization between about 10 and 100,000 which are homo- or copolymers soluble in water or a swelling index in the range from 10 to 500. 3. Polymer according to claim 2, characterized in that the polymer is prepared from a monoethylenically unsaturated acrylic acid of the general formula R ch 2 = c-cooh 78 1 24 2 5 16 Λ in which Η is a substituent selected from the group consisting of hydrogen, halogen, hydroxy, lactone, lactam cyano, alkyl, aryl, aralkyl, alkylaryl or cycloalkyl. 4. Polymer according to claim 3, characterized in that the polymer is water-soluble. ^ 5. Polymer according to claim 3, characterized in that the polymer has a swelling index in the range of about 10 to 500. 6. Polymer according to claim 4, characterized in that the polymer is prepared from methacrylic acid. Polymer according to claim, characterized in that the polymer is prepared from acrylic acid and a cross-linking agent selected from the group consisting of 1,1.1-trimethylol-propane-trimethacrylate, vinyl crotonate, polyallyl sugars, triethanolamine triacrylate or styrene. 75 Polymer according to claim 4 (1) characterized in that the polymer is prepared from ethylene and maleic anhydride. 9. A process for the preparation of a pharmaceutical preparation, characterized in that the product according to claim 1 and / or the non-toxic, pharmacologically acceptable salts thereof, is brought into a form suitable for such use. Parmaceutical preparation, characterized in that the product of claim 1 and / or its non-toxic pharmaceutically acceptable salts thereof are suitable carriers. 11. A composition according to claim 10, characterized in that the composition contains a unit dose of from 0.1 g to about 20 g of a water-soluble or colloidal water-soluble homopolymer or copolymer or mixtures thereof, prepared from a monomer or monomers selected from a group consisting of ethylenically unsaturated carboxylic acids containing at least one ethylenic double bond and at least one carboxyl group, the polymer having a degree of polymerization within the range of from about 10 to about 100,000 and a swelling index from about 10 to about 500 , and the non-toxic, pharmacologically acceptable salts thereof. 78 1 24 2 5