POLYMER MEDICAMENT FOR TREATING HYPERKALEMIA AND PREPARATION METHOD THEREOF

Abstract

Provided are a polymer medicament for treating hyperkalemia, and a preparation method thereof. Specifically, a polymer is provided, and the polymer includes repeating units obtained by polymerizing a monomer and a crosslinking agent. A molar ratio of the monomer to the crosslinking reagent ranges from 1:0.02 to 1:0.20. The monomer includes an acidic group and a pKa-reducing group next to the acidic group. The acidic group is selected from the group consisting of sulfonic acid group (—SO.sub.3—), sulfuric acid group (—OSO.sub.3—), carboxylic group (—CO.sub.2—), phosphonic acid group (—OPO.sub.3.sup.2—), phosphate group (—OPO.sub.3.sup.2—), and sulfamic acid group (—NHSO.sub.3—). The pKa-reducing group is selected from the group consisting of nitro, cyano, carbonyl, trifluoromethyl, and halogen atoms. The crosslinking agent has three or four reaction sites. The polymer can be used to treat hyperkalemia.

Claims

1. A polymer, comprising repeating units obtained by polymerizing a monomer and a crosslinking agent, wherein a molar ratio of the monomer to the crosslinking agent ranges from 1:0.02 to 1:0.20, and the monomer comprises an acidic group and a pKa-reducing group next to the acidic group, wherein the acidic group is selected from the group consisting of a sulfonic acid group (—SO.sub.3—), a sulfuric acid group (—OSO.sub.3—), a carboxylic group (—CO.sub.2—), a phosphonic acid group (—OPO.sub.3.sup.2—), a phosphate group (—OPO.sub.3.sup.2—), and a sulfamic acid group (—NHSO.sub.3—); the pKa-reducing group is selected from the group consisting of nitro, cyano, carbonyl, trifluoromethyl, and halogen atoms; and the crosslinking agent has three or four reaction sites.

2. The polymer according to claim 1, wherein the acidic group is the carboxylic group, and the pKa-reducing group is fluorine.

3. The polymer according to claim 1, wherein the reaction sites are free alkenyl groups.

4. The polymer according to claim 1, wherein the crosslinking agent comprises at least one of triallyl isocyanurate, 1,2,4-trivinylcyclohexane, tetravinylsilane, trimethylolpropane trimethacrylate, triallyl cyanurate, or triallylcarbinol.

5. The polymer according to claim 1, wherein the polymer is at least one selected from the group consisting of polyvinyl sulfonic acid polymer, polyvinyl sulfamic acid polymer, poly(vinyl sulfamic acid/vinyl sulfuric acid) copolymer, polyvinyl amino phosphonic acid polymer, N-(bisphosphonate ethyl) polyvinylamine polymer, poly(α-fluoroacrylic acid) polymer, vinylphosphonic acid/acrylic acid copolymer, vinylphosphonic acid/α-fluoroacrylic acid copolymer, polyvinylsulfuric acid polymer, and cross-linked polyvinylsulfamic acid polymer.

6. A polymer, having a structure represented by formula (I) or being a salt of the structure represented by formula (I): ##STR00020## wherein, R.sub.1 is ##STR00021## when R.sub.1 contains three binding sites, R.sub.2 is not present; and when R.sub.1 contains four binding sites, R.sub.2 is connected to one of the four binding sites of R.sub.1 and R.sub.2 is ##STR00022## m ranges from 0.80 to 0.98, n ranges from 0.02 to 0.20, and m+n=1; n.sub.1, n.sub.2, n.sub.3, n.sub.4, and n.sub.5 are each independently selected from 0, 1, 2, 3, 4, 5, 6, or 7; X.sub.1, X.sub.2, X.sub.5, X.sub.4, X.sub.5, and X.sub.6 are each independently a carbon atom or a nitrogen atom; m1 is 0 or 1; and * represents a binding site.

7. The polymer according to claim 6, wherein R.sub.1 is ##STR00023##

8. The polymer according to claim 6, wherein R.sub.1 is ##STR00024##

9. A polymer, having any one of the following structures or being a salt of any one of the following structures: ##STR00025## wherein m ranges from 0.80 to 0.98; n ranges from 0.02 to 0.20; and m+n=1.

10. A pharmaceutical composition, comprising the polymer according to claim 1, and a pharmaceutically acceptable excipient.

11. A method for reducing potassium in a subject, comprising administrating the polymer according to claim 1 to the subject.

12. A method for treating or preventing hyperkalemia in a subject, comprising administrating a therapeutic effective amount of the polymer according to claim 1 to the subject.

13. The method according to claim 12, wherein the hyperkalemia is caused by administration of a medicament that causes potassium retention.

14. The method according to claim 13, wherein the medicament that causes potassium retention is selected from the group consisting of non-potassium diuretics, angiotensin-converting enzyme inhibitors, non-steroidal anti-inflammatory drugs, heparin, and trimethoprim.

15. The method according to claim 13, wherein the polymer is in a form of a pharmaceutical composition containing a pharmaceutically acceptable excipient.

16. A potassium ion adsorption determination method, comprising: detecting an adsorption capacity of the polymer according to any claim 1 for potassium ions through ion chromatography.

17. A method for treating or preventing hyperkalemia in a subject, comprising administrating a therapeutic effective amount of the polymer according to claim 6 to the subject.

18. The method according to claim 17, wherein the hyperkalemia is caused by administration of a medicament that causes potassium retention.

19. A method for treating or preventing hyperkalemia in a subject, comprising administrating a therapeutic effective amount of the polymer according to claim 9 to the subject.

20. The method according to claim 19, wherein the hyperkalemia is caused by administration of a medicament that causes potassium retention.

21. A pharmaceutical composition, comprising the polymer according to claim 6, and a pharmaceutically acceptable excipient.

22. A pharmaceutical composition, comprising the polymer according to claim 9, and a pharmaceutically acceptable excipient.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0068] The above and/or additional aspects and advantages of the present disclosure will become apparent and easy to understand from the description of embodiments in conjunction with the following drawing:

[0069] FIG. 1 is a diagram showing that Sodium zirconium cyclosilicate and MFA-TAIC polymer could reduce the increase of urine K.sup.+ induced by KCl.

[0070] FIG. 2 is a diagram showing that Sodium zirconium cyclosilicate and MFA-TAIC polymer significantly increased fecal K.sup.+ excretion (P<0.001, P<0.001).

DESCRIPTION OF EMBODIMENTS

[0071] The present disclosure is described below with reference to specific embodiments. It should be noted that these embodiments are only descriptive and do not limit the present disclosure in any way.

[0072] The following abbreviations are used throughout the present disclosure:

[0073] MFA: methyl 2-fluoroacrylate; PVA: polyvinyl alcohol; BPO: benzoyl peroxide; TAIC: 15 triallyl isocyanurate; TVS: tetravinylsilane; DGDE: diethylene glycol divinyl ether; DADMS: diallyldimethylsilane; EGDMA: ethylene glycol dimethacrylate; TMPTMA: trihydroxymethylpropyl trimethacrylate; DPGDA: dipropylene glycol diacrylate; DVB: divinylbenzene; and ODE: octadiene.

[0074] A positive drug used in the present disclosure is sodium zirconium cyclosilicate 20 (Lokelma), a commercial product from AstraZenca/AndersonBrecon. Inc., batch No.: LJ2076A.

[0075] The crosslinking agents used in the present disclosure are listed in Table 1.

TABLE-US-00001 TABLE 1 No. Name Abbreviation Structural formula  (1) Triallyl isocyanurate TAIC [00007]  (3) Tetravinylsilane TVS [00008]  (4) 1,2,4-trivinylcyclohexane TVCH [00009]  (5) Diethylene glycol divinyl ether DGDE [00010]  (6) Diallyldimethylsilane DADMS [00011]  (7) Ethylene glycol dimethacrylate EGDMA [00012]  (8) Trihydroxymethylpropyl trimethacrylate TMPTMA [00013]  (9) Dipropylene glycol diacrylate DPGDA [00014] (10) Divinylbenzene DVB [00015] (11) Octadiene ODE [00016]

Example 1

[0076] ##STR00017##

[0077] 550 mL of purified water and 3.4 g of PVA were added to a reaction flask, and dissolved by stirring at 20° C. to 30° C. until they were completely dissolved clarification. MFA solution was prepared as below: 104.08 g of MWA, 14.08 g of TAIC, and 0.85 g of BPO were stirred and completely dissolved clarification for later use. The prepared MFA solution was added into the reaction flask. The reaction temperature was gradually increased to 70° C. to 80° C., followed by holding the temperature and stirring for 15 h. After the temperature was reduced to 20° C. to 30° C., suction filtration was performed. The filter cake was pulped and washed respectively with 1 L water and 1 L ethanol, 3 times each. The obtained wet product was vacuum-dried at 50° C. to obtain 101.0 g of a white solid, i.e., MFA-TAIC polymer ester.

[0078] 400 mL of water, 50.4 g of lithium hydroxide monohydrate, and 150 mL of tetrahydrofuran were added to a reaction flask, and then the above MFA-TAIC polymer ester was added under stirring. The temperature was increased to 50° C. to 60° C., followed by stirring and holding the temperature for 15 h. The temperature was lowered to 20° C. to 30° C., then filtration was performed, and the filter cake was pulped and washed with water and ethanol. A lithium salt wet product of MFA-TAIC polymer was obtained by the filtration.

[0079] 500 mL of water and 100 mL of concentrated hydrochloric acid were added to a reaction flask, the above-mentioned lithium salt wet product of MFA-TAIC polymer was added, followed by stirring for 15 h at 20° C. to 30° C. After the filtration, the filter cake was pulped and washed with water. The wet product obtained after filtration was pulped once with 500 mL of ethanol. The wet product obtained after filtration was vacuum-dried at 50° C. for 8 h to obtain 91.0 g of white dry product, which was crushed and sieved through a 120-mesh sieve, to obtain the finished product of the MFA-TAIC(m=0.95, n=0.05) polymer.

Example 2

[0080] ##STR00018##

[0081] 550 mL of purified water and 3.4 g of PVA were added to a reaction flask, and dissolved by stirring at 20° C. to 30° C. until they were completely dissolved clarification. An MFA solution 15 was prepared as below: 104.0 g of MFA, 6.8 g of TVS, and 0.85 g of BPO were stirred and completely dissolved clarification for later use. The prepared MFA solution was added into the reaction flask. The temperature of the materials in the reaction flask was gradually increased to 70° C. to 80° C., followed by holding the temperature and stirring for 15 h. After the temperature was reduced to 20° C. to 30° C., suction filtration was performed. The filter cake was pulped and washed with water. The obtained wet product was dried to obtain 90.2 g of a white solid, i.e., MFA-TVS polymer ester.

[0082] 400 mL of water and 50.4 g of lithium hydroxide monohydrate were added to a reaction flask, and then the above MFA-TVS polymer ester was added under stirring. The temperature was increased to 50° C. to 60° C., followed by stirring and holding the temperature for 15 h. The temperature was lowered to 20° C. to 30° C., then filtration was performed, and the filter cake was pulped and washed with water. The filtered wet product was a lithium salt wet product of MFA-TVS polymer.

[0083] 500 mL of water and 100 mL of concentrated hydrochloric acid were added to a reaction flask, the above-mentioned lithium salt wet product of MFA-TVS polymer was added, followed by stirring for 15 h at 20° C. to 30° C. After filtration, the filter cake was repeatedly washed with water. The wet product obtained after filtration was pulped once with ethanol. The wet product obtained after filtration was vacuum-dried at 50° C. for 8 h to obtain 79.4 g of white dry product, which was crushed and sieved through a 120-mesh sieve, to obtain the finished product of the MFA-TVS (m=0.95, n=0.05) polymer.

Example 3

[0084] ##STR00019##

[0085] 550 mL of purified water and 3.4 g of PVA were added to a reaction flask, and dissolved by stirring at 20° C. to 30° C. until they were completely dissolved clarification. An MFA solution was prepared as below: 104.0 g of MFA, 8.1 g of TVCH, and 0.85 g of BPO were stirred and completely dissolved clarification for later use. The prepared MFA solution was added into the reaction flask. The temperature of the materials in the reaction flask was gradually increased 70° C. to 80° C., followed by holding the temperature and stirring for 15 h. After the temperature was reduced to 20° C. to 30° C., suction filtration was performed. The filter cake was pulped and washed with water. The obtained wet product was dried to obtain 101.2 g of a white solid, i.e., MFA-TVCH polymer ester.

[0086] 400 mL of water and 50.4 g of lithium hydroxide monohydrate were added to a reaction flask, and then the above MFA-TVCH polymer ester was added under stirring. The temperature was increased to 50° C. to 60° C., followed by stirring and holding the temperature for 15 h. The temperature was lowered to 20° C. to 30° C., then filtration was performed, and the filter cake was pulped and washed with water. The filtered wet product was a lithium salt wet product of MFA-TVCH polymer.

[0087] 500 mL of water and 100 mL of concentrated hydrochloric acid were added to a reaction flask, the above-mentioned lithium salt wet product of MFA-TVCH polymer was added, followed by stirring for 15 h at 20° C. to 30° C. After filtration, the filter cake was repeatedly washed with water. The wet product obtained after filtration was pulped once with ethanol. The wet product obtained after filtration was vacuum-dried at 50° C. for 8 h to obtain 82.7 g of a white dry product, which was crushed and sieved through a 120-mesh sieve, to obtain the finished product of the MFA-TVCH (m=0.95, n=0.05) polymer.

Example 4

[0088] 550 mL of purified water and 3.4 g of PVA were added to a reaction flask, and dissolved by stirring at 20° C. to 30° C. until they were completely dissolved clarification. An MFA solution was prepared as below: 104.0 g of MFA, 6.5 g of DVB, and 0.85 g of BPO were stirred and completely dissolved clarification for later use. The prepared MFA solution was added into the reaction flask. The temperature of the materials in the reaction flask was gradually increased to 70° C. to 80° C., followed by holding the temperature and stirring for 15 h. After the temperature was reduced to 20° C. to 30° C., suction filtration was performed. The filter cake was pulped and washed with water. The obtained wet product was dried to obtain 112.0 g of a white solid, i.e., MFA-DVB polymer ester.

[0089] 400 mL of water and 50.4 g of lithium hydroxide monohydrate were added to a reaction flask, and then the above MFA-DVB polymer ester was added under stirring. The temperature was increased to 50° C. to 60° C., followed by stirring and holding the temperature for 15 h. The temperature was lowered to 20° C. to 30° C., then filtration was performed, and the filter cake was pulped and washed with water. The filtered wet product was a lithium salt wet product of MFA-DVB polymer.

[0090] 500 mL of water and 100 mL of concentrated hydrochloric acid were added to a reaction flask, the above-mentioned lithium salt wet product of MFA-DVB polymer was added, followed by stirring for 15 h at 20° C. to 30° C. After filtration, the filter cake was repeatedly washed with 4 L of water. The wet product obtained after filtration was pulped once with 500 mL of ethanol. The wet product obtained after filtration was dried at 50° C. for 8 h to obtain 82.3 g of a white dry product, which was crushed and sieved through a 120-mesh sieve, to obtain the finished product of the MFA-DVB (m=0.95, n=0.05) polymer.

Example 5

[0091] 550 mL of purified water and 3.4 g of PVA were added to a reaction flask, and dissolved by stirring at 20° C. to 30° C. until they were completely dissolved clarification. An MFA solution was prepared as below: 104.0 g of MFA, 5.5 g of ODE, and 0.85 g of BPO were stirred and completely dissolved clarification for later use. The prepared MFA solution was added into the reaction flask. The temperature of the materials in the reaction flask was gradually increased to 70° C. to 80° C., followed by holding the temperature and stirring for 15 h. After the temperature was reduced to 20° C. to 30° C., suction filtration was performed. The filter cake was pulped and washed with water. The obtained wet product was dried to obtain 107.0 g of a white solid, i.e., MFA-ODE polymer ester.

[0092] 400 mL of water and 50.4 g of lithium hydroxide monohydrate were added to a reaction flask, and then the above MFA-ODE polymer ester was added under stirring. The temperature was increased to 50° C. to 60° C., followed by stirring and holding the temperature for 15 h. The temperature was lowered to 20° C. to 30° C., then filtration was performed, and the filter cake was pulped and washed with water. The filtered wet product was a lithium salt wet product of MFA-ODE polymer.

[0093] 500 mL of water and 100 mL of concentrated hydrochloric acid were added to a reaction flask, the above-mentioned lithium salt wet product of MFA-ODE polymer was added, followed by stirring for 15 h at 20° C. to 30° C. After filtration, the filter cake was repeatedly washed with 4 L of water. The wet product obtained after filtration was pulped once with 500 mL of ethanol. The wet product obtained after filtration was dried at 50° C. for 8 h to obtain 80.3 g of a white dry product, which was crushed and sieved through a 120-mesh sieve, to obtain the finished product of the MFA-ODE (m=0.95, n=0.05) polymer.

Example 6

[0094] 550 mL of purified water and 3.4 g of PVA were added to a reaction flask, and dissolved by stirring at 20° C. to 30° C. until they were completely dissolved clarification. An MFA solution was prepared as below: 104.0 g of MFA, 14.0 g of TAIC, and 0.85 g of BPO were stirred and 20 completely dissolved clarification for later use. The prepared MFA solution was added into the reaction flask. The temperature of the materials in the reaction flask was gradually increased to 70° C. to 80° C., followed by holding the temperature and stirring for 15 h. After the temperature was reduced to 20° C. to 30° C., suction filtration was performed. The filter cake was pulped and washed with water. The obtained wet product was dried to obtain 101.0 g of a white solid, i.e., MFA-TAIC polymer ester.

[0095] 400 mL of water and 48.0 g of sodium hydroxide were added to a reaction flask, and then the above MFA-TAIC polymer ester was added under stirring. The temperature was increased to 50° C. to 60° C., followed by stirring and holding the temperature for 15 h. The temperature was lowered to 20° C. to 30° C., then filtration was performed, and the filter cake was pulped and washed with 1 L of water 3 times. The filtered wet product was a sodium salt wet product of MFA-TAIC polymer. The wet product obtained after filtration was dried at 50° C. for 12 h to obtain 93.7 g of a white dry product, which was crushed and sieved through a 120-mesh sieve, to obtain the finished product of the MFA-TAIC (m=0.95, n=0.05) polymer.

Example 7

[0096] 550 mL of purified water and 3.4 g of PVA were added to a reaction flask, and dissolved by stirring at 20° C. to 30° C. until they were completely dissolved clarification. An MFA solution was prepared as below: 104.0 g of MFA, 14.0 g of TAIC, and 0.85 g of BPO were stirred and completely dissolved clarification for later use. The prepared MFA solution was added into the reaction flask. The temperature of the materials in the reaction flask was gradually increased to 70° C. to 80° C., followed by holding the temperature and stirring for 15 h. After the temperature was reduced to 20° C. to 30° C., suction filtration was performed. The filter cake was pulped and washed with water. The obtained wet product was dried to obtain 101.0 g of a white solid, i.e., MFA-TAIC polymer ester.

[0097] 400 mL of water and 48.0 g of sodium hydroxide were added to a reaction flask, and then the above MFA-TAIC polymer ester was added under stirring. The temperature was increased to 50° C. to 60° C., followed by stirring and holding the temperature for 15 h. The temperature was lowered to 20° C. to 30° C., then filtration was performed, and the filter cake was pulped and washed with water. The filtered wet product was a sodium salt wet product of MFA-TAIC polymer.

[0098] The filtered wet product was added to 1 L of water, 333.0 g of anhydrous calcium chloride was added, followed by pulping and stirring at 20° C. to 30° C. for 6 h. The filtered wet product was repeatedly pulped and washed with 1 L water 3 times. The filtered wet product was added with 1 L of water and 333.0 g of anhydrous calcium chloride, followed by pulping and stirring at 20° C. to 30° C. for 6 h. The filtered wet product was repeatedly pulped with 1 L of water until the conductivity was ≤50 μs/cm. After suction filtration, the wet product was dried at 50° C. for 18 h to obtain 99.2 g of a white dry product, which was crushed and sieved through a 120-mesh sieve, to obtain the finished product of the MFA-TAIC calcium salt (m=0.95, n=0.05) polymer.

Example 8

[0099] Potassium buffer: potassium buffer was prepared with 150 mmol/L potassium and 200 mmol/L 2-[morpholino] ethanesulfonic acid, the pH was 6.0 to 8.0.

[0100] Standard graph: Identify five 100 m1 volumetric flasks by the numbers 1, 2, 3, 4, and 5. In that order pipet 1, 3, 6. 8, and 10 mL of potassium buffer into the flasks, dilute with water to volume, and mix. Perform ion chromatography detection on volumetric flasks 1, 2, 3, 4, and 5 and record the peak area of potassium ion. On ruled coordinate paper, plot the observed peak area as the ordinate, and the concentrations, in mmol per liter, of potassium as the abscissa.

[0101] Test sample solution: Take about 1.6 g of polymer, place it in a 250 m1 Erlenmeyer flask, add 100 m1 of potassium buffer, water bath at 37° C. 2° C., stir with magnet for 24 h, shake evenly, sample (15 min, 3 h, 5 h or 24 h as recommended), filter, precisely pipet 1 ml of filtrate into a 100 m1 volumetric flask, and dilute to the mark with water.

[0102] Analyze test sample solution by ion chromatography and record the peak area of potassium ion, and determine the potassium concentration, in mmol per liter, by interpolation from the Standard graph. Calculate the adsorption amount, in mmol per g, of potassium ion adsorbed on the resin taken by the formula:

Potassium ion adsorption amount of polymer=(X−2.5Y)/W

in which X is the weight, in mmol, of potassium in 100 mL of Potassium solution before exchange; Y is the weight, in mmol, of potassium per L as interpolated from the Standard graph; and W is the weight, in g, of polymer taken, expressed on the anhydrous basis.

[0103] The chromatographic conditions are listed in Table 2 below.

TABLE-US-00002 TABLE 2 Chromatographic CS16, CS17, CS12A (250 mm × 4 mm) column protection column CG16, CG17, CG12A (50 mm × 4 mm) Detector Electrical conductivity detector Suppressor CSRS 4 mm Flow rate 0.3 to 5 ml/min, preferably 1.0 ml/min Column temperature 30° C. Current 18 mA Detector temperature 35° C. Injection volume 10 to 100 μl, preferably 10 μl Eluent Methanesulfonic acid solution, preferably 6 mM Running time 20 min

[0104] Results and Analysis

[0105] The potassium ion adsorption capacities of the polymers in Examples 1, 2, 3 and 5 were measured with this method, as shown in Table 3 below.

TABLE-US-00003 TABLE 3 Potassium ion adsorption amount of polymer Example No. (mmol/g) Example 1 (MFA-TAIC) 7.5 Example 2 (MFA-TVS) 7.5 Example 3 (MFA-TVCH) 7.7 Example 5 (MFA-ODE) 6.7 Sodium zirconium cyclosilicate 3.6 (commercial product from AstraZenca) Veltassa (commercial 2.6 product from Relypsa)

[0106] Conclusion: It can be seen from the above table that the polymer prepared by using the crosslinking agent with three or four reaction sites in the present disclosure has a significantly higher potassium ion-adsorption capacity than the polymer prepared by using the crosslinking agent with two reaction sites, and significantly higher than the polymers known in the related art.

Example 9

[0107] The samples listed in Table 4 below were placed in an aluminum plastic bag for Stability test (25° C.±2° C./60% RH±5% RH, 40° C.±2° C./75% RH±5% RH), and the results are shown in Table 4.

TABLE-US-00004 TABLE 4 Accelerated Accelerated Free fluoride stability test stability test Material ion content (25° C. ± 2° C./ (40° C. ± 2° C./ name Process (μg/g) (day 0) 60% RH ± 5% RH) 75% RH ± 5% RH) Example 1 MFA-TAIC 36.0 Placed at 25° C. for 2 Placed at 40° C. for 2 months, the free months, the free fluoride ion content fluoride ion content not increased not increased Veltassa Commercial 14.3 Placed at 25° C. for 2 Placed at 40° C. for 2 product from months, the free months, the free Relypsa (batch fluoride ion content fluoride ion content number significantly significantly CCWVX) increased, 8.0 times increased, 25.1 times that on day 0 that on day 0

[0108] It can be seen from the above table that the polymers of the present disclosure have high stability, which is significantly higher than the polymer of the related art.

Example 10

[0109] 32 normal male SD rats were reared adaptively for 3-5 days and then randomly divided into 4 groups, i.e., a normal group, a model group, a positive control group (sodium zirconium cyclosilicate), a MFA-TAIC polymer group, each group including 8 rats. In accordance with intragastric administration at a volume of 20 m1/kg, the normal group was administered with a corresponding solvent (0.1% xanthan gum), the positive control group was administered with sodium zirconium cyclosilicate at 1.5 g/kg, the MFA-TAIC polymer group was administered with 10 MFA-TAIC polymer at 1.5 g/kg, for only one time. The model group, the positive control group (sodium zirconium cyclosilicate), and the MFA-TAIC polymer group were respectively intraperitoneally injected with 10% KCl at a volume of 4 m1/kg 3 hours after the administration, and then supplemented with 5% KCl solution every 1 hour, continuously for 8 hours, i.e., supplemented with KCl solution 8 times. Before the administration, 3 hours after the administration (i.e., before the modeling (0 h)), and 1 h, 2 h, 4 h, 6 h, and 8 h after the modeling, 0.4 mL of whole blood was collected from the orbit, serum was separated, and blood potassium level was detected. All animals were individually placed in metabolic cages, and urine and faeces within 24 hours after administration were collected on the next day to detect potassium ion content. If the blood collection and KCl injection had conflicts in term of time, the blood was collected 2 minutes in advance, and then KCl was intraperitoneally injected on time after the blood collection. If deaths occurred, the time and number of deaths were recorded. The faeces were freeze-dried, and the weight of dried faeces of each rat was recorded. Cations in the faeces were extracted with 1M HCl overnight. Then, the ion chromatography analysis was performed.

[0110] The results showed that compared with the normal group, the urine K.sup.+ level in the model group was significantly increased (P<0.05), and sodium zirconium cyclosilicate and MFA-TAIC polymer could reduce the increase of urine K.sup.+ induced by KCl, as shown in FIG. 1. Compared with normal group, K.sup.+ in faeces of model group increased to a certain extent, increasing by 79.87%, with no statistical difference. Compared with the normal group, sodium zirconium cyclosilicate and MFA-TAIC polymer increased fecal K.sup.+ excretion (P<0.001, P<0.001), and compared with the model group, sodium zirconium cyclosilicate and MFA-TAIC polymer increased fecal K.sup.+ excretion (P<0.001, P<0.001), as shown in FIG. 2.

[0111] In the specification, descriptions with reference to the terms “an embodiment”, “some embodiments”, “examples”, “specific examples”, or “some examples”, etc. mean that specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present disclosure. In this specification, the above terms are illustrative, and do not necessarily refer to the same embodiment or example. Moreover, the described specific features, structures, materials or characteristics can be combined in a suitable manner in any one or more embodiments or examples. In addition, those skilled in the art can combine different embodiments or examples and the features of the different embodiments or examples described in this specification without contradicting each other.

[0112] Although the embodiments of the present disclosure are illustrated and described above, it can be understood that the above-mentioned embodiments are illustrative and should not be construed as limitations of the present disclosure. Those skilled in the art can make changes, modifications, substitutions, and variations to the above-mentioned embodiments within the scope of the present disclosure.