CN103159880A - Preparation method for sevelamer carbonate - Google Patents
Preparation method for sevelamer carbonate Download PDFInfo
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- CN103159880A CN103159880A CN2011104170440A CN201110417044A CN103159880A CN 103159880 A CN103159880 A CN 103159880A CN 2011104170440 A CN2011104170440 A CN 2011104170440A CN 201110417044 A CN201110417044 A CN 201110417044A CN 103159880 A CN103159880 A CN 103159880A
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Abstract
The present invention relates to a preparation method for sevelamer carbonate, comprising: reacting allylamine and hydrochloric acid to give allylamine hydrochloride, then polymerizing to form an allylamine hydrochloride polymer under the initiation of an azo initiator, then alkalizing to obtain an allylamine polymer, then reacting with epichlorohydrin to synthesize sevelamer hydrochloride, and finally neutralizing to free the sevelamer hydrochloride which reacts with carbonic acid to give the sevelamer carbonate. The preparation method for the sevelamer carbonate of the present invention is stable in reactions, short in cycle, cheap in raw materials, high in yield, and less harmful to the environment, thereby being suitable for industrial production.
Description
Technical field
The present invention relates to a kind of synthetic method of polymer class medicine, relate in particular to a kind of preparation method who treats the 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate of kidney exhaustion.
Background technology
2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate (Sevelamer carbonate), chemical name: Sevelamer carbonate,
2-Propen-1-amine polymer with (chloromethyl) oxirane carbonate, structural formula is seen formula III: wherein a, b: primary amine group number; C: the quantity of crosslinking structure; N: the quantity of hydrochloride; M: a large amount of indications extend polymer network,
（III）
This product is a kind of new phosphate binders, have nonabsorbable, not calcic, do not contain aluminium, can avoid the characteristics of gastrointestinal absorption and degraded; And positively charged, with combination, cause draining in ight soil phosphorus increases entrained a plurality of amidos by the phosphoric acid in ion-exchange and hydrogen bond and small intestine in the small intestine inner proton, thereby reduces serium inorganic phosphorus and the other high level of Tiroidina.
Find after deliberation: using sevelamer to treat front and back, in the patients serum, phosphorus content is respectively 2.81 ± 0.71 m mol/l and 2.06 ± 0.61 m mol/l, uses sevelamer to change on average that in serum, phosphorus content is about-0.71 ± 0.77 m mol/l(P＜0.0001); Before and after treatment, Determination of Calcium in Serum content is respectively 2.28 ± 0.20 m mol/l and 2.35 ± 0.20 m mol/l, on average changes serum calcium 0.08 ± 0.22 m mol/l(P＜0.0001); Before and after treatment, calcium-phosphorus product (Ca x P product) is respectively 6.32 ± 1.60 m mol/l and 4.86 ± 1.45 m mol/l, and average calcium-phosphorus product changes-1.46 ± 1.78 m mol/l(P＜0.0001); And low-density lipoprotein (LDL) concentration that shows serum to reduce by 0.82 ± 0.74 m mol/l(average-30%, P＜0.0001), high-density lipoprotein (HDL) (HDL) concentration on average increases by 0.15 ± 0.29mmol/l (average+18%, P＜0.0001).
Hemodialysis patient the scholar arranged by be studies show that, through sevelamer and lime acetate (calcium acetate) after eight weeks for the treatment of, it is similar that both reduce the degree of serum paraoxonase, the average change is respectively sevelamer :-2.0 ± 2.3mg/d(P＜0.0001), lime acetate :-2.1 ± 1.9 mg/dl (P＜0.0001); But use patients serum's calcium concn of sevelamer obviously lower, have serum calcium cancentration greater than 11.0 mg/dl(〉 2.75mmol/l) the sevelamer patient of situation 5 % are arranged, compare, use the patient of lime acetate up to 22 %(P＜0.0001).Find in the Parathyroid hormone research that reached for 44 weeks, sevelamer is to complete section high parathyroid hormone (intact PTH is called for short iPTH) (〉 300 pg/ml) splendid reduction effect arranged; But can improve iPTH concentration when low iPTH, and not cause hypercalcemia, have very greatly and benefit so be considered to for inferior property Parathyroid ergogenic processing.Other studies show that sevelamer has the LDL(that lowers 37 % serum and infers that it may be combined with cholic acid), and attenuating 22 % total cholesterol density of serum, but do not affect serum triacylglycerol TG or HDL concentration, and reduce the formation of hemodialysis patient angiosteosis and reduce the effect of mortality ratio.Also have in addition many clinical studyes to prove that all sevelamer can control serum paraoxonase and the calcium-phosphorus product of dialysis patient, simultaneously serum calcium is had less impact, less side effect is arranged.
Summary of the invention
The reaction scheme that the purpose of this invention is to provide a kind of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate is short, and yield is high, is fit to the preparation method of suitability for industrialized production.
The preparation method of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate of the present invention comprises the following steps:
Step 1 changes into salt with allylamine and concentrated hydrochloric acid reaction acid and obtains allylamine hydrochloride;
Step 2, allylamine hydrochloride generation polymerization forms the allylamine salt acid polymer as shown in the formula I;
Step 3, allylamine salt acid polymer and alkali reaction alkalization obtain the allyl amine polymer as shown in the formula II;
Step 4, allyl amine polymer and epichlorohydrin reaction synthetic hydrochloric acid sevelamer;
Step 5, sevelamer hydrochloride first obtain the sevelamer of free state with the alkaline solution neutralization, then react with arbon dioxide solution, obtain 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate
；
。
（I） （II）
In a preferred embodiment of the present invention, also comprise initiator in described step 2, described initiator is azo compound type initiator.
In another preferred embodiment of the present invention, described azo compound type initiator is selected from 2.2 '-azo (2-amidine propane) dihydrochloride, 2,2'-azo diisobutyl amidine dihydrochloride, azo di-isopropyl imidazoline salt hydrochlorate.
In another preferred embodiment of the present invention, the temperature of reaction of described step 2 is 88 ~ 90
oC。
In another preferred embodiment of the present invention, 24 ~ 28 hours reaction times of described step 2.
In another preferred embodiment of the present invention, added phase-transfer catalyst in described step 4.
In another preferred embodiment of the present invention, described phase-transfer catalyst is sorbitan fatty acid ester.
In another preferred embodiment of the present invention, the weight ratio of described allyl amine polymer, sorbitan fatty acid ester and epoxy chloropropane is 1:1.2:0.8.
In another preferred embodiment of the present invention, the reaction times of described step 4 is 10 ~ 15 hours.
In another preferred embodiment of the present invention, in described step 3, alkali is the KOH aqueous solution; In step 5, alkaline solution is the 30%NaOH aqueous solution.
The preparation method of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate of the present invention, stable reaction, the cycle is short, raw material is cheap, and yield is high, less to the harm of environment, be suitable for suitability for industrialized production.
Embodiment
Below with reference to embodiment, the present invention is done detailed explaination.
The synthesis route of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate of the present invention is as follows: take allylamine as starting raw material, through acidifying becomes salt formation allylamine hydrochloride monomer with hydrochloric acid reaction, and then under the initiation of azo-compound, the generation polymerization forms allylamine salt acid polymer, then alkalization obtains allyl amine polymer, and synthesizes the sevelamer hydrochloride with epichlorohydrin reaction; Sevelamer hydrochloride dissociates through alkalization and makes 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate with the carbonic acid reaction.
Specifically, above-mentioned steps of the present invention can be realized by following reaction:
1) knee supports and foot supports (starting raw material SM) and concentrated hydrochloric acid reaction obtains allylamine hydrochloride (A);
Knee supports and foot supports and concentrated hydrochloric acid are reacted in solvent, and temperature of reaction is 40 ~ 50
oC, the reaction times is 3 ~ 4 hours, reaction after finishing removes solvent under reduced pressure, obtains the allylamine hydrochloride monomer; Wherein the weight ratio of allylamine and concentrated hydrochloric acid is 1:10, reacts selected solvent and can be tetrahydrofuran (THF), methyl alcohol or water, particular methanol.
2) self-polymerization of allylamine hydrochloride reaction obtains allylamine salt acid polymer (B);
Cause with initiator, in preferred azo-compound initiator 2.2 '-azo (2-amidine propane) dihydrochloride (Va-086), 2,2'-azo diisobutyl amidine dihydrochloride (Va-050), azo di-isopropyl imidazoline salt hydrochlorate (Va-044), the allylamine hydrochloride monomer is dissolved in solvent self polymerization occurs, temperature of reaction is 88 ~ 90
oC, the reaction times is 24 ~ 28 hours.After reaction finishes, cooling, slowly be added drop-wise to solution and carry out crystallization in methyl alcohol, is added dropwise to complete rear continuation and stirred 5 ~ 6 hours, filters the allylamine hydrochloride polymkeric substance that obtains white.Wherein the weight ratio of allylamine hydrochloride monomer and azo-compound initiator is 1:1, and reaction solvent is tetrahydrofuran (THF), methyl alcohol or water, preferably water; Yield is 70% ~ 80%.
3) allylamine salt acid polymer and alkali reaction obtain allyl amine polymer (C);
Allylamine hydrochloric acid polymer dissolution is formed solution in water, slowly drip alkali in this solution, the preferred KOH aqueous solution, regulating the pH value is 9 ~ 13, temperature adjustment to 20 ~ 40
oC stirred 3 ~ 4 hours, after reaction finishes, and the aqueous solution of the allyl amine polymer that obtains dissociating.Wherein the weight ratio of allylamine salt acid polymer and KOH is 1:1, and solvent is tetrahydrofuran (THF) or water, preferably water.
4) allyl amine polymer and epichlorohydrin reaction obtain sevelamer hydrochloride (D);
Under the effect of sorbitan fatty acid ester (span-85), allyl amine polymer and epoxy chloropropane react in solvent, and temperature of reaction is 30 ~ 50
oC, the reaction times is 10 ~ 15 hours, after reaction finishes, have a large amount of solids in solution and occur, filter, filter cake rinses with tetrahydrofuran (THF), the white that obtains or class yellow powder shape solid carry out drying under reduced pressure, finally obtain the sevelamer hydrochloride of white or class yellow crystalline powder shape.Wherein the weight ratio of allyl amine polymer, span-085 and epoxy chloropropane is 1:1.2:0.8, and reaction solvent is toluene or tetrahydrofuran (THF), preferred toluene.The yield of sevelamer hydrochloride is more than 95%.
5) sevelamer hydrochloride through in alkaline solution and after free, then with the carbonic acid reaction, obtain 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate (E);
Sevelamer hydrochloride (D) and 30%NaOH solution reaction, the pH that reacts final is 11 ~ 13.Pass into carbon dioxide again in system, till pH regulator to 7 ~ 8(pH is no longer changed).Reaction has a large amount of solids and separates out after finishing in solution, filter, and the filter cake water rinses, and the white that obtains or class yellow powder shape solid carry out drying under reduced pressure, finally obtain the sevelamer carbonate of white or class yellow crystalline powder shape.Wherein the weight ratio of sevelamer hydrochloride, 30%NaOH solution and water is 1:0.24:10.
For the ease of unification, all material ratios of the present invention are weight ratio, and namely 1:1 is the weight ratio of solid and liquid.
Characteristics of the present invention:
1, the present invention by knee supports and foot supports as starting raw material, through persalt salify, self-polymerization.Because the self-polymerization reaction itself has uncontrollability, so reaction has been carried out certain screening to initiator, temperature of reaction and time.
2, polymkeric substance after free with the reaction process of epoxy chloropropane in, because the difference of selective solvent can produce homogeneous phase and heterogeneous 2 kinds of situations, span-085 is this thinks that transfer catalyst comes accelerated reaction so increased, and also reaction times and quantity of solvent is screened simultaneously.
3, to have reaction time short due to this reaction, and raw material is cheap, and to characteristics such as the harm of environment are less, therefore be well suited for for suitability for industrialized production.
Embodiment 1
1) add the 100.0g allylamine in reaction vessel, be warming up to 40 ~ 50 ℃, water-soluble 1000 g of 36% hydrochloric acid are added drop-wise in container.After being added dropwise to complete, continue to stir 30 minutes to 1 hour.Detect pH value (pH=1 ~ 2).Reaction times amounts to 3 ~ 4 hours.At the temperature of 80 ℃, be evaporated to absence of liquid and ooze, weigh.
2) add 300g water in reaction vessel, be warming up to 88 ~ 90 ℃; Under nitrogen protection, add 300.0gVa-044 is disposable, stirred 24 ~ 28 hours.Reaction changes reaction solution in the constant pressure dropping funnel over to after finishing.Reaction solution slowly is added drop-wise in 500g methyl alcohol separates out white solid.After being added dropwise to complete, continue to stir 5 ~ 6 hours.Filter under nitrogen protection, obtain white crystal, decompression drying lower than 100 ℃ the time.Obtain the allylamine hydrochloride polymkeric substance, be weighed as 110g, nitrogen protection, yield is 110%.
3) change allylamine hydrochloride polymkeric substance 96g over to reaction vessel, add 144g water.Control temperature at 20 ~ 30 ℃.50%KOH solution 26.88g is slowly joined in reaction system.Being added dropwise to complete rear continuation stirred 3 ~ 4 hours.Detect pH value (pH=9 ~ 13), be warmed up to 20 ~ 40 ℃.
4) add 960g toluene, 115g span-085 in reaction system, continue to stir 1 ~ 2 hour, filter.Mother liquor changes reaction vessel over to.Temperature is risen to 30 ~ 50 ℃.Add the 77g epoxy chloropropane.Continue to stir 10 ~ 15 hours.Filter.Filter cake changes reaction vessel over to.Add 200g water in reaction vessel, stirred 30 minutes ~ 1 hour.Filter, filter cake changes in reaction vessel.Add 300g water in reaction vessel.Stirred 30 minutes ~ 1 hour, and filtered.The analyzing and testing result.The filter cake oven dry obtains 91.2g sevelamer hydrochloride salt light yellow solid, and yield is 95%.Allylamine hydrochloride polymkeric substance wherein, the weight ratio of span-085 and epoxy chloropropane is 1:1.2:0.8.
5) add 100g sevelamer hydrochloride salt and 1000g water in the reactant container, regulate pH to 11 ~ 13 with 30%NaOH solution.Under whipped state, pass into carbonic acid gas in reaction system, regulate pH to 7 ~ 8, after reaction finishes, filter the analyzing and testing result.The filter cake oven dry obtains 100g 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate salt light yellow solid, and weight yield is 100%.Wherein the weight ratio of sevelamer hydrochloride salt and water is 1:10, and the usage quantity of carbonic acid gas is calculated according to final pH.
According to above technique, knee supports and foot supports can obtain highly purified 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, and calculates with the yield of per step reaction, and the yield of final carbonate synthesis sevelamer is up to 100%.
Embodiment 2
1) add the 120.0g allylamine in reaction vessel, be warming up to 40 ~ 50 ℃, water-soluble 1200 g of 36% hydrochloric acid are added drop-wise in container.After being added dropwise to complete, continue to stir 30 minutes to 1 hour.Detect pH value (pH=1 ~ 2).Reaction times amounts to 3 ~ 4 hours.At the temperature of 80 ℃, be evaporated to absence of liquid and ooze, weigh.
2) add 310g water in reaction vessel, be warming up to 88 ~ 90 ℃; Under nitrogen protection, add 300.0gVa-050 is disposable, stirred 24 ~ 28 hours.Reaction changes reaction solution in the constant pressure dropping funnel over to after finishing.Reaction solution slowly is added drop-wise in 600g methyl alcohol separates out white solid.After being added dropwise to complete, continue to stir 5 ~ 6 hours.Filter under nitrogen protection, obtain white crystal, decompression drying lower than 100 ℃ the time.Obtain the allylamine hydrochloride polymkeric substance, be weighed as 112g, nitrogen protection, yield is 102%.
3) change allylamine hydrochloride polymkeric substance 112g over to reaction vessel, add 150g water.Control temperature at 20 ~ 30 ℃.50%KOH solution 27.24g is slowly joined in reaction system.Being added dropwise to complete rear continuation stirred 3 ~ 4 hours.Detect pH value (pH=9 ~ 13), be warmed up to 20 ~ 40 ℃.
4) add 960g toluene, 120g span-085 in reaction system, continue to stir 1 ~ 2 hour, filter.Mother liquor changes reaction vessel over to.Temperature is risen to 30 ~ 50 ℃.Add the 80.20g epoxy chloropropane.Continue to stir 10 ~ 15 hours.Filter.Filter cake changes reaction vessel over to.Add 200g water in reaction vessel, stirred 30 minutes ~ 1 hour.Filter, filter cake changes in reaction vessel.Add 300g water in reaction vessel.Stirred 30 minutes ~ 1 hour, and filtered.The analyzing and testing result.The filter cake oven dry obtains the 139g light yellow solid, and yield is 95%.Allylamine hydrochloride polymkeric substance wherein, the weight ratio of span-085 and epoxy chloropropane is 1:1.2:0.8.
5) add 120g sevelamer hydrochloride salt and 1200g water in the reactant container, regulate pH to 11 ~ 13 with 30%NaOH solution.Under whipped state, pass into carbonic acid gas in reaction system, regulate pH to 7 ~ 8, after reaction finishes, filter the analyzing and testing result.The filter cake oven dry obtains 120g 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate salt light yellow solid, and weight yield is 100%.Wherein the weight ratio of sevelamer hydrochloride salt and water is 1:10, and the usage quantity of carbonic acid gas is calculated according to final pH.
According to above technique, knee supports and foot supports can obtain highly purified 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, and calculates with the yield of per step reaction, and the yield of final carbonate synthesis sevelamer is up to 100%.
Embodiment 3
1) add the 90g allylamine in reaction vessel, be warming up to 40 ~ 50 ℃, the water-soluble 1000g of 36% hydrochloric acid is added drop-wise in container.After being added dropwise to complete, continue to stir 30 minutes to 1 hour.Detect pH value (pH=1 ~ 2).Reaction times amounts to 3 ~ 4 hours.At the temperature of 80 ℃, be evaporated to absence of liquid and ooze, weigh.
2) add 300g water in reaction vessel, be warming up to 88 ~ 90 ℃; Under nitrogen protection, add 300.0gVa-086 is disposable, stirred 24 ~ 28 hours.Reaction changes reaction solution in the constant pressure dropping funnel over to after finishing.Reaction solution slowly is added drop-wise in 500g methyl alcohol separates out white solid.After being added dropwise to complete, continue to stir 5 ~ 6 hours.Filter under nitrogen protection, obtain white crystal, decompression drying lower than 100 ℃ the time.Obtain the allylamine hydrochloride polymkeric substance, be weighed as 95.4g, nitrogen protection, yield is 99%.
3) change allylamine hydrochloride polymkeric substance 95.4g over to reaction vessel, add 154g water.Control temperature at 20 ~ 30 ℃.50%KOH solution 25.78g is slowly joined in reaction system.Being added dropwise to complete rear continuation stirred 3 ~ 4 hours.Detect pH value (pH=9 ~ 13), be warmed up to 20 ~ 40 ℃.
4) add 960g toluene, 110g span-085 in reaction system, continue to stir 1 ~ 2 hour, filter.Mother liquor changes reaction vessel over to.Temperature is risen to 30 ~ 50 ℃.Add the 76.5g epoxy chloropropane.Continue to stir 10 ~ 15 hours.Filter.Filter cake changes reaction vessel over to.Add 200g water in reaction vessel, stirred 30 minutes ~ 1 hour.Filter, filter cake changes in reaction vessel.Add 300g water in reaction vessel.Stirred 30 minutes ~ 1 hour, and filtered.The analyzing and testing result.The filter cake oven dry obtains the 135.8g light yellow solid, and yield is 95.6%.Allylamine hydrochloride polymkeric substance wherein, the weight ratio of span-085 and epoxy chloropropane is 1:1.2:0.8.
5) add 90g sevelamer hydrochloride salt and 1000g water in the reactant container, regulate pH to 11 ~ 13 with 30%NaOH solution.Under whipped state, pass into carbonic acid gas in reaction system, regulate pH to 7 ~ 8, after reaction finishes, filter the analyzing and testing result.The filter cake oven dry obtains 90g 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate salt light yellow solid, and weight yield is 100%.Wherein the weight ratio of sevelamer hydrochloride salt and water is 1:10, and the usage quantity of carbonic acid gas is calculated according to final pH.
According to above technique, knee supports and foot supports can obtain highly purified 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, and calculates with the yield of per step reaction, and the yield of final carbonate synthesis sevelamer is up to 100%.
Above specific embodiments of the invention are described in detail, but it is just as example, the present invention is not restricted to specific embodiment described above.To those skilled in the art, any equivalent modifications that the present invention is carried out and substituting also all among category of the present invention.Therefore, not breaking away from impartial conversion and the modification of doing under the spirit and scope of the present invention, all should contain within the scope of the invention.
Claims (10)
1. the preparation method of a 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, is characterized in that, comprises the following steps:
Step 1 changes into salt with allylamine and concentrated hydrochloric acid reaction acid and obtains allylamine hydrochloride;
Step 2, allylamine hydrochloride generation addition polymerization forms the allylamine salt acid polymer as shown in the formula I;
Step 3, allylamine salt acid polymer and alkali reaction alkalization obtain the allyl amine polymer as shown in the formula II;
Step 4, allyl amine polymer and epichlorohydrin reaction synthetic hydrochloric acid sevelamer;
Step 5, sevelamer hydrochloride first obtain the sevelamer of free state with the alkaline solution neutralization, then react with arbon dioxide solution, obtain 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate;
2.（I） （II）
The preparation method of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate as claimed in claim 1 is characterized in that, comprises also in described step 2 that initiator, described initiator are azo compound type initiator.
3. the preparation method of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate as claimed in claim 2, it is characterized in that, described azo compound type initiator is selected from 2.2 '-azo (2-amidine propane) dihydrochloride, 2,2'-azo diisobutyl amidine dihydrochloride, azo di-isopropyl imidazoline salt hydrochlorate.
4. the preparation method of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate as claimed in claim 1, is characterized in that, the temperature of reaction of described step 2 is 88 ~ 90
oC。
5. the preparation method of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate as claimed in claim 1, is characterized in that, 24 ~ 28 hours reaction times of described step 2.
6. the preparation method of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate as claimed in claim 1, is characterized in that, added phase-transfer catalyst in described step 4.
7. the preparation method of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate as claimed in claim 6, is characterized in that, described phase-transfer catalyst is sorbitan fatty acid ester.
8. the preparation method of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate as claimed in claim 7, is characterized in that, the weight ratio of described allyl amine polymer, sorbitan fatty acid ester and epoxy chloropropane is 1:1.2:0.8.
9. the preparation method of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate as claimed in claim 1, is characterized in that, the reaction times of described step 4 is 10 ~ 15 hours.
10. the preparation method of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate as claimed in claim 1, is characterized in that, in described step 3, alkali is the KOH aqueous solution; In step 5, alkaline solution is the 30%NaOH aqueous solution.
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Cited By (4)
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|---|---|---|---|---|
| CN103694389A (en) * | 2013-12-10 | 2014-04-02 | 山东新华制药股份有限公司 | Sevelamer carbonate preparation technology |
| CN105732865A (en) * | 2016-03-04 | 2016-07-06 | 扬州天和药业有限公司 | Preparation process of sevelamer carbonate |
| CN108440697A (en) * | 2018-04-11 | 2018-08-24 | 常州方圆制药有限公司 | A kind of synthetic method of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate |
| CN113045693A (en) * | 2021-03-25 | 2021-06-29 | 山东新华制药股份有限公司 | Preparation method of sevelamer carbonate |
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| WO2010029579A2 (en) * | 2008-09-15 | 2010-03-18 | Shasun Chemicals And Drugs Ltd | Non-aqueous solution process for the preparation of cross-linked polymers |
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| US20100331516A1 (en) * | 2008-04-08 | 2010-12-30 | Govind Dhananjay Sathe | Process for Preparation of Sevelamer Carbonate |
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| CN101304739A (en) * | 2005-11-08 | 2008-11-12 | 基酶有限公司 | Magnesium-containing polymers for hyperphosphatemia |
| US20100331516A1 (en) * | 2008-04-08 | 2010-12-30 | Govind Dhananjay Sathe | Process for Preparation of Sevelamer Carbonate |
| WO2010029579A2 (en) * | 2008-09-15 | 2010-03-18 | Shasun Chemicals And Drugs Ltd | Non-aqueous solution process for the preparation of cross-linked polymers |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103694389A (en) * | 2013-12-10 | 2014-04-02 | 山东新华制药股份有限公司 | Sevelamer carbonate preparation technology |
| CN103694389B (en) * | 2013-12-10 | 2016-08-17 | 山东新华制药股份有限公司 | Sevelamer carbonate preparation technology |
| CN105732865A (en) * | 2016-03-04 | 2016-07-06 | 扬州天和药业有限公司 | Preparation process of sevelamer carbonate |
| CN108440697A (en) * | 2018-04-11 | 2018-08-24 | 常州方圆制药有限公司 | A kind of synthetic method of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate |
| CN113045693A (en) * | 2021-03-25 | 2021-06-29 | 山东新华制药股份有限公司 | Preparation method of sevelamer carbonate |
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| CN103159880B (en) | 2016-06-22 |
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Effective date of registration: 20160810 Address after: 201202, Shanghai, Nanhui, Pudong New Area new town around the lake west two, No. 2, building 2, district 3013, room 888 Patentee after: Shanghai Anse Biotechnology Co. Ltd. Address before: 201315, No. 3188, Lane 88, Sau Pu Road, Cambridge Town, Shanghai, Pudong New Area Patentee before: Eterpharm (Shanghai), Inc. |