CN103393610A - Preparation for quickly disintegrating fatty amine polymer salt - Google Patents
Preparation for quickly disintegrating fatty amine polymer salt Download PDFInfo
- Publication number
- CN103393610A CN103393610A CN2013102824849A CN201310282484A CN103393610A CN 103393610 A CN103393610 A CN 103393610A CN 2013102824849 A CN2013102824849 A CN 2013102824849A CN 201310282484 A CN201310282484 A CN 201310282484A CN 103393610 A CN103393610 A CN 103393610A
- Authority
- CN
- China
- Prior art keywords
- amine polymer
- propen
- chloromethyl
- carbonate
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a preparation for quickly disintegrating fatty amine polymer salt, and particularly relates to a sevelamer carbonate tablet. The formula of the preparation comprises the following components: 400-800g of sevelamer carbonate, 40-80g of microcrystalline cellulose, 40-80g of sodium hydrogen carbonate, 10-20g of arginine, 10-20g of polylactic acid and 1-2g of magnesium stearate. The preparation method comprises the following steps: preparing the active component (sevelamer carbonate) and the auxiliary components for later use; uniformly mixing the sevelamer carbonate, the microcrystalline cellulose, the sodium hydrogen carbonate, the arginine and the polylactic acid; adding water, and uniformly mixing; granulating through a dry method; then adding the magnesium stearate, and uniformly mixing; and tabletting.
Description
Technical field
The present invention relates to a kind of pharmaceutical preparation, particularly a kind of aliphatic amine polymer salt fast disintegrating preparations and preparation method thereof.
Background technology
Aliphatic amine polymer salt, as: 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, sevelamer hydrochloride, colesevelam hydrocholoride, colestipol hydrochloride, hydrochloric acid colestyramine, because in structure, containing aliphatic amine polymer, cause absorbing difficulty, preparation is difficult to manufacture especially, so fast disintegrating preparations is important selection.
But when preparing fast disintegrating preparations, other problems is comed one after another, as runs into the problems such as stability, gastrointestinal tract effect, phosphoric acid combination rate while preparing the 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate fast disintegrating preparations.
2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, a kind of aliphatic amine polymer, English name: Sevelamer carbonate, structural formula:
A, b=primary amine groups number (a+b=9)
C=crosslinked group number (c=1)
The derivatized polymers that the m=large number extends with expression
Molecular formula: (C
3H
7NnH
2CO
3)
810Z(C
9H
18N
2OnH
2CO
3)
95Z
(z is a very large numeral)
2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate is a kind ofly not absorb, and the phosphate binders of calcic not, in order to substitute the sevelamer hydrochloride that uses that gone through
The chemical composition of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, for poly-(the third alkene ammonia ?is ?N altogether, basic ?1, the 3 two ammonia base ?2 ?hydroxy propanes of N ' ?bis-alkene third) carbonate, comprises multiple amine groups, and the carbon that is aggregated on the thing skeleton separates.Amine is protonated in gastrointestinal tract, so these positive charges can be in conjunction with negative ion in intestinal, the phosphate that for example discharges in digestion process.Phosphorus can not absorb in blood after polymer, dissociating, by intestinal, in the feces mode, drain.2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate (tablet) is approved in the U.S. chronic kidney disease (CKD) patient who controls the reception dialysis and controls the serum paraoxonase level.
It is that the interior serum paraoxonase hydrochlorate level of human body is greater than about 4.5mg/dL that hyperphosphatemia typically defines.To renal function deficiency disease, disease and other medical symptom that hyperparathyroidism is relevant, often be accompanied by hyperphosphatemia.If this situation long-term existence surpasses certain hour, can cause the serious abnormality of calcium and phosphorus metabolism, and performance, be the abnormal calcification effect on joint, lung and eyes.Hyperphosphatemia can bring out serious cardiovascular disease, is the key factor that the End-stage Renal Disease Patients mortality rate increases.
Chinese patent CN101043878B is very short for the tablet shelf life of being made by aliphatic amine polymer carbonate, introducing the supplementary a kind of monovalent anion source of fatty amine carbonate tablet to can be significantly, increase shelf life, and under the standard storage condition, can prevent the increase of disintegration time during storage.And further find that the particle size that increases aliphatic amine polymer granule in tablet can increase shelf life significantly, and can prevent that disintegration time is along with the time changes and increases during storage under the standard storage condition.
The inventor is studied 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, discovery is in the tablet of preparation, 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate is in storage process, the amount of carbonate is reducing, affect the stability of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate time of staying in gastrointestinal tract while is short, has limited the larger effect in conjunction with phosphorus of its performance.
The present invention finds through research, in tablet formulation by after adding sodium bicarbonate, the content of the carbonate in 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate no longer descends, in tablet, add and contain the more arginine of amino group simultaneously, can make the larger effect in conjunction with phosphorus of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate performance, add polylactic acid that 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate time of staying in gastrointestinal tract is extended, thereby greatly improved its ability in conjunction with phosphorus.
Summary of the invention
The invention provides a kind of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate tablet, its formula is composed as follows:
Its preparation method is as follows:
Preparation method of the present invention comprises the following steps, and gets active component 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate and adjunct ingredient and gets the raw materials ready, and is standby; Get 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, microcrystalline Cellulose, sodium bicarbonate, arginine, polylactic acid mix homogeneously, add the water mix homogeneously, dry granulation, then add magnesium stearate, mix homogeneously, be pressed into 1000 and get final product.
Wherein microcrystalline Cellulose plays quick disintegration, and sodium bicarbonate plays stablizes the 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate effect, and arginine plays increases the effect of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate curative effect, and polylactic acid plays and extends gastrointestinal tract delay effect.
Formula of the present invention obtains through screening, and screening process is as follows:
One, the selection of formula:
The inventor is studied 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, discovery is in the tablet of preparation, 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate is in storage process, the amount of carbonate is reducing, affect the stability of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate tablet, determine to add sodium bicarbonate, by increasing the content of carbonate, guarantee the stability of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate tablet, improve simultaneously disintegration.
The inventor thinks through research, in 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, amino plays a decisive role in medicine, but because of the 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate molecular weight large, be loaded with amino amount limited, the inventor wishes to improve by increasing amino amount the effectiveness of medicine, add the maximum arginine of amino content in aminoacid for this reason, with the curative effect of investigating medicine, whether increase.
The inventor thinks through research, and 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate is mainly in its effect of gastrointestinal tract, for increasing its time in gastrointestinal tract, selected polylactic acid as improving at the reagent of gastrointestinal tract holdup time and having carried out relevant experimentation.
The formula that the present invention selects is as follows:
Table 1, the different formulations list:
Preparation method adopts the method for embodiment 2 to be prepared into 1000 tablets of tablets.
| Formula | Formula 1 | Formula 2 | Formula 3 | Formula 4 | Formula 5 |
| 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate | 800g | 800g | 800g | 800g | 800g |
| Microcrystalline Cellulose | 80g | 80g | 80g | 80g | 80g |
| Sodium bicarbonate | 80g | ? | 80g | 80g | 80g |
| Arginine | 20g | 20g | ? | 20g | ? |
| Polylactic acid | 20g | 20g | 20g | ? | ? |
| Magnesium stearate | 2g | 2g | 2g | 2g | 2g |
Two, the stability experiment of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate tablet
By formula 1 ?5 tablet put 60 ℃ to place 0 day, 10 days, the content results that detected 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate in 30 days as follows:
| 60℃ | Formula 1 | Formula 2 | Formula 3 formula 4 formulas 5 | Prior art formula |
| 0 day | 99.28% | 99.65% | 99.46%?99.74%?99.23% | 99.36% |
| 10 days | 99.14% | 98.54% | 98.13%?97.35%?97.26% | 97.68% |
| 30 days | 98.93% | 97.38% | 97.10%?96.42%?96.31% | 96.67% |
Three, the combination experiment of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate tablet and phosphate radical
By formula 1 ?5 tablet porphyrize, take 0.1g, stable precision, put in the 100ml measuring bottle, with phosphate standard inventory solution, be settled to scale, stirred 15 minutes, with the microporous filter membrane of 0.22 μ m, filter, 100 times of upper solution dilutions, use ion-chromatographic determination, result is as follows:
Four, 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate tablet gastrointestinal tract is detained experiment
By formula 1 ?5 tablet to rat, take, through 6 hours, 12 hours, put to death respectively rat, get its harmonization of the stomach intestinal, add water to 100ml, soaked 2 hours, stir, centrifugal, get supernatant, with ion-chromatographic determination 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate content, result is as follows: unit: (μ g/ml)
Through above research, the present invention has prepared a kind of new fast disintegrating preparations, has solved defect of the prior art, as stability, gastrointestinal tract effect, the problems such as phosphoric acid combination rate, oral result is good, simple to operate, easy to use, easily and the phosphorus in food, calcium, the combination of magnesium plasma, in conjunction with effective, reach good therapeutic effect.
The specific embodiment
Be below detailed specific description of the present invention, but do not limit scope of invention.
Embodiment 1
The tablet that contains sevelamer carbonate, write out a prescription as follows:
Preparation method comprises the following steps, and gets active component 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate and adjunct ingredient and gets the raw materials ready, and is standby; Get 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, microcrystalline Cellulose, sodium bicarbonate, arginine, polylactic acid mix homogeneously, add the water mix homogeneously, dry granulation, then add magnesium stearate, mix homogeneously, be pressed into 1000 and get final product.
Embodiment 2
The tablet that contains sevelamer carbonate, write out a prescription as follows:
Preparation method comprises the following steps, and gets active component 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate and adjunct ingredient and gets the raw materials ready, and is standby; Get 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, microcrystalline Cellulose, sodium bicarbonate, arginine, polylactic acid mix homogeneously, add the water mix homogeneously, dry granulation, then add magnesium stearate, mix homogeneously, be pressed into 1000 and get final product.
Claims (3)
1. 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate tablet, its formula is composed as follows:
Its preparation method is as follows:
Get active component 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate and adjunct ingredient and get the raw materials ready, standby; Get 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, microcrystalline Cellulose, sodium bicarbonate, arginine, polylactic acid mix homogeneously, add the water mix homogeneously, dry granulation, then add magnesium stearate, mix homogeneously, be pressed into 1000 and get final product.
2. tablet that contains sevelamer carbonate, write out a prescription as follows:
Its preparation method is as follows:
Get active component 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate and adjunct ingredient and get the raw materials ready, standby; Get 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, microcrystalline Cellulose, sodium bicarbonate, arginine, polylactic acid mix homogeneously, add the water mix homogeneously, dry granulation, then add magnesium stearate, mix homogeneously, be pressed into 1000 and get final product.
3. tablet that contains sevelamer carbonate, write out a prescription as follows:
Its preparation method is as follows:
Get active component 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate and adjunct ingredient and get the raw materials ready, standby; Get 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, microcrystalline Cellulose, sodium bicarbonate, arginine, polylactic acid mix homogeneously, add the water mix homogeneously, dry granulation, then add magnesium stearate, mix homogeneously, be pressed into 1000 and get final product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310282484.9A CN103393610B (en) | 2013-07-05 | 2013-07-05 | Preparation for quickly disintegrating fatty amine polymer salt |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310282484.9A CN103393610B (en) | 2013-07-05 | 2013-07-05 | Preparation for quickly disintegrating fatty amine polymer salt |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103393610A true CN103393610A (en) | 2013-11-20 |
| CN103393610B CN103393610B (en) | 2014-12-24 |
Family
ID=49557476
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310282484.9A Active CN103393610B (en) | 2013-07-05 | 2013-07-05 | Preparation for quickly disintegrating fatty amine polymer salt |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103393610B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017215608A1 (en) * | 2016-06-14 | 2017-12-21 | Teligene Ltd | Sevelamer carbonate for tableting |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7749536B2 (en) * | 2006-02-14 | 2010-07-06 | Teva Pharmaceutical Industries Ltd. | Pharmaceutical formulations of aliphatic amine polymers and methods for their manufacture |
| CN101835500A (en) * | 2007-08-29 | 2010-09-15 | 吸附剂治疗学公司 | Absorbent polymeric compositions with varying counterion content and their methods of preparation and use |
| CN102824322A (en) * | 2004-11-01 | 2012-12-19 | 基酶有限公司 | Aliphatic amine polymer salts for tableting |
| EP2545907A1 (en) * | 2011-07-15 | 2013-01-16 | Combino Pharm, S.L. | Aqueous wet granulation process for cross-linked polyallylamine polymers |
-
2013
- 2013-07-05 CN CN201310282484.9A patent/CN103393610B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102824322A (en) * | 2004-11-01 | 2012-12-19 | 基酶有限公司 | Aliphatic amine polymer salts for tableting |
| US7749536B2 (en) * | 2006-02-14 | 2010-07-06 | Teva Pharmaceutical Industries Ltd. | Pharmaceutical formulations of aliphatic amine polymers and methods for their manufacture |
| CN101835500A (en) * | 2007-08-29 | 2010-09-15 | 吸附剂治疗学公司 | Absorbent polymeric compositions with varying counterion content and their methods of preparation and use |
| EP2545907A1 (en) * | 2011-07-15 | 2013-01-16 | Combino Pharm, S.L. | Aqueous wet granulation process for cross-linked polyallylamine polymers |
Non-Patent Citations (1)
| Title |
|---|
| 朱珠: "降血磷新药———司维拉姆", 《中国药学杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017215608A1 (en) * | 2016-06-14 | 2017-12-21 | Teligene Ltd | Sevelamer carbonate for tableting |
| CN109715142A (en) * | 2016-06-14 | 2019-05-03 | 苏州韬略生物科技有限公司 | 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate for tabletting |
| CN109715142B (en) * | 2016-06-14 | 2021-10-12 | 苏州韬略生物科技有限公司 | Sevelamer carbonate for tableting |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103393610B (en) | 2014-12-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102908325B (en) | Sevelamer carbonate medical tablet composition and preparation method thereof | |
| Mokhtari et al. | Water compatible molecularly imprinted polymer for controlled release of riboflavin as drug delivery system | |
| CN102145062B (en) | Active extracts of rosa roxburghii tratt fruit, and preparation method, detection method and application thereof | |
| CN102133225B (en) | Compound polyethylene glycol electrolyte pulvis and preparation method thereof | |
| CN102641251B (en) | Underwater-dispersible tablet of Sevelamer carbonate | |
| CN104546781A (en) | Sevelamer carbonate tablet and preparation method thereof | |
| CN103393610A (en) | Preparation for quickly disintegrating fatty amine polymer salt | |
| CN105193803A (en) | Ilepcimide sustained release preparation and preparation method thereof | |
| Ahn et al. | Transient fanconi syndrome after treatment with firocoxib, cefadroxil, tramadol, and famotidine in a maltese | |
| CN103239636A (en) | Application of reed rhizome extract and gingerol in preparation of attenuated synergistic medicines for cancer chemotherapy | |
| CN102499934A (en) | Application of 3-methoxy xanthone compound in preparation of medicament for preventing and treating hyperuricemia | |
| CN103127041A (en) | Medicinal composition with lanthanum acetate, preparation method and application thereof | |
| CN103120654A (en) | Application of lanthanum acetate or hydrates for treating hyperphosphatemia | |
| CN104739786B (en) | 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate tablet and preparation method | |
| CN102813661B (en) | Application for glycyrrhetinic acid derivatives | |
| CN102579733A (en) | Compound traditional Chinese medicine powder for treating sow constipation | |
| CN101152262B (en) | New anti-gout medicinal preparation | |
| CN105287513A (en) | Ezetimibe medicine composition and preparation method thereof | |
| CN103494782A (en) | Ganciclovir tablet and preparation method thereof | |
| CN104825406B (en) | Preparation process of sevelamer hydrochloride tablets | |
| CN102973577B (en) | Compound sodium sulfaquinoxaline composition for treating coccidiosis in young rabbits, and preparation method thereof | |
| CN103864972A (en) | Preparation method of sevelamer carbonate | |
| CN105357966A (en) | Method and products for enhancing drug and dietary supplement bioavailability | |
| CN115040554B (en) | Application of wu Su Liwa Wei Zonghuang ketone | |
| CN103356478A (en) | Ibuprofen injection composition and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CP02 | Change in the address of a patent holder |
Address after: No. 1018 Liaohe Road, Xinbei District, Changzhou City, Jiangsu Province, 213000 Patentee after: CHANGZHOU FANGYUAN PHARMACEUTICAL Co.,Ltd. Address before: 213022 Jiangsu city of Changzhou province Hehai Road New District No. 108 Patentee before: CHANGZHOU FANGYUAN PHARMACEUTICAL Co.,Ltd. |
|
| CP02 | Change in the address of a patent holder |