CN108743546A - A kind of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent and preparation method thereof - Google Patents
A kind of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent and preparation method thereof Download PDFInfo
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- CN108743546A CN108743546A CN201810683078.6A CN201810683078A CN108743546A CN 108743546 A CN108743546 A CN 108743546A CN 201810683078 A CN201810683078 A CN 201810683078A CN 108743546 A CN108743546 A CN 108743546A
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- amine polymer
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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Abstract
The present invention relates to a kind of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agents, by weight comprising the following raw material component：100 parts of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, 400-600 parts of filler, 50-70 parts of suspending agent, 10-20 parts of corrigent.2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent prepared by prescription using the present invention and technique, even particle distribution, stability are good, dissolve out, is in good taste；And patient's serium inorganic phosphorus concentration can be maintained in the long period, while reducing and taking number, improve the compliance of patient.
Description
Technical field
The invention belongs to medication chemistry technologies to synthesize field, and in particular to a kind of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent and its system
Preparation Method.
Background technology
2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate piece (FDA approval listing drug commodity beThe approval time is October 19 in 2007
Day) it is as marketed products sevelamer hydrochloride piece (trade nameIt is U.S. Gel TexPharmaceuticals
Inc. I kind new medicine of company's development and production, on October 30th, 1998 are ratified to list by U.S. FDA) substitute products, and it is a kind of
Nonabsorbable phosphate binders without calcium, without metal, but it has the carbonate buffer system beneficial to body.One is intended to
The clinical test for comparing Rensivela and Renagel shows, KDOQI chronic kidney disease and dialysis of two kinds of drugs in recommendation
In the range of clinical practice guideline, control serum phosphorus levels effect is identical.Sevelamer Carbonate or sevelamer HCl are equal
It is polymeric anion exchanger resin.Although ion balance (salt) is different, polymer of two kinds of compounds itself (can be with phosphorus knot
The active part of conjunction) it is identical.
It has been investigated that 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate is not soluble in water, but has hydrophily, volume significantly expansion and Cheng Ning after water are met
It is gluey.The dosage form of presently commercially available 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate is mainly tablet, and tablet volume is smaller, is convenient for carrying, but due to carbonic acid
Sevelamer raw material compressibility is poor, and therefore, auxiliary material proportion is higher to cause tablet volume larger, for the patient of dysphagia
Medication brings larger trouble.
CN107375218A discloses a kind of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate oral sustained-release dry suspension, contains 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate
30~50%, suspending agent 25%~35%, filler 15~25%, adhesive 5~10%, magnesium stearate 2~5%, sucrose 0.1
~1%, titanium dioxide 0.1~1%.Although the dry suspensoid agent of the patent has preferable slow release effect, its slow release effect
And redispersibility still needs to be further increased.
Invention content
In order to overcome the problems, such as in the prior art, the present invention provides a kind of slow release effect and the good carbonic acid department dimension of redispersibility
Draw nurse dry suspensoid agent and preparation method thereof.
In order to solve the above technical problems, the present invention adopts the following technical scheme that：
It is an object of the present invention to provide a kind of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agents, by weight comprising as follows
Raw material components：100 parts of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, 400-600 parts of filler, 50-70 parts of suspending agent, 10-20 parts of corrigent.
Preferably, by weight comprising the following raw material component：100 parts of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, helps 500 parts of filler
60 parts of suspension, 15 parts of corrigent.
Preferably, one kind in sucrose, lactose, mannitol, starch, xylitol, maltitol of the filler or
It is two or more.
Preferably, the suspending agent be selected from sodium carboxymethylcellulose, sodium alginate, one or both of povidone with
On.
It is further preferred that the suspending agent be sodium alginate and povidone composition, and the mass ratio of the two be 1~
3:1。
Most preferably, the sodium alginate and the mass ratio of the povidone are 2:1, it is prepared into this, as suspending agent
The dry suspensoid agent sedimentation volume ratio arrived is maximum, and redispersibility is best.
Preferably, the corrigent is selected from one or more of Aspartame, fragrant citrus essence, trisodium citrate.
It is further preferred that the corrigent is Aspartame, fragrant citrus essence, trisodium citrate are 1~3 by weight:
0.5~1.5:The mixture of 1 composition.
Most preferably, the weight ratio of the Aspartame, the fragrant citrus essence, the trisodium citrate is 2:1:1, this
Invention is found, by selecting above-mentioned specific corrigent, can not only well solve 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent
Sensory issues, and it was unexpectedly observed that also have it is rapid-action, contribute to the effect of the stability of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent
Fruit.
It is a further object to provide a kind of preparation methods of the 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent, including
Following steps：
(1) 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate is sieved with 100 mesh sieve, filler, suspending agent and corrigent is crossed to 80 mesh sieve respectively；
(2) by 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, filler, suspending agent and the corrigent after sieving, add water and be uniformly mixed, prepare soft
Material；The sieve granulation of 25 mesh, 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent is obtained after dry.
Compared with prior art, the invention has the advantages that：
2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent prepared by prescription using the present invention and technique is even particle distribution, steady
It is qualitative it is good, dissolve out, be in good taste；And patient's serium inorganic phosphorus concentration can be maintained in the long period, while reducing and taking number, it improves
The compliance of patient.
Specific implementation mode
It is noted that following detailed description is all illustrative, it is intended to provide further instruction to the application.Unless another
It indicates, all technical and scientific terms used herein has usual with the application person of an ordinary skill in the technical field
The identical meanings of understanding.
In order to enable those skilled in the art can clearly understand the technical solution of the application, below with reference to tool
The technical solution of the application is described in detail in the embodiment of body.
Test material used in the embodiment of the present invention is the test material of this field routine, can pass through commercial channel
It is commercially available.
Embodiment 1：
1. raw material prescription：
100 grams of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, 500 grams of filler, 60 grams of suspending agent, 15 grams of corrigent.
Wherein, filler is mannitol, and suspending agent is the composition of sodium alginate and povidone, and the mass ratio of the two is 2:
1；Corrigent is Aspartame, fragrant citrus essence, trisodium citrate are 2 by weight:1:The mixture of 1 composition.
2. preparation process：
(1) 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate is sieved with 100 mesh sieve, filler, suspending agent and corrigent is crossed to 80 mesh sieve respectively；
(2) by 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, filler, suspending agent and the corrigent after sieving, add water and be uniformly mixed, prepare soft
Material；The sieve granulation of 25 mesh, 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent is obtained after dry.
Embodiment 2：
1. raw material prescription：
100 grams of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, 600 grams of filler, 50 grams of suspending agent, 20 grams of corrigent.
Wherein, filler is lactose, and suspending agent is sodium carboxymethylcellulose；Corrigent is Aspartame, fragrant citrus essence, lemon
Lemon acid trisodium is 2 by weight:1:The mixture of 1 composition.
2. preparation process：
Preparation process is the same as embodiment 1.
Embodiment 3：
1. raw material prescription：
100 grams of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, 400 grams of filler, 70 grams of suspending agent, 10 grams of corrigent.
Wherein, filler is sucrose, and suspending agent is sodium alginate；Corrigent is Aspartame, fragrant citrus essence, citric acid three
Sodium is 2 by weight:1:The mixture of 1 composition.
2. preparation process：
Preparation process is the same as embodiment 1.
Test example 1：Dry suspensoid agent settling property and suspension performance test
According to《Chinese Pharmacopoeia》Regulation of the version in relation to dry suspensoid agent sedimentation volume ratio is tested within 2010, the results are shown in Table 1.
Table 1
As can be seen from Table 1,2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent sedimentation volume ratio of the present invention is all higher than 0.9, meets pharmacopeia
Regulation, and the dry suspensoid agent for the composition preparation that suspending agent is sodium alginate and povidone, redispersibility are significantly better than other
Dry suspensoid agent prepared by suspending agent.
Test example 2：Hyperphospheremia rat in vivo studies
9 hyperphospheremia rats are selected, 190-200 grams of weight, every 3 are one group, and gastric infusion gives embodiment 1- respectively
3 dry suspensoid agent, in the 0th, 0.5,1,2,4,6,8,10,12, extracting vein blood 1ml for 24 hours, measure phosphorus content (mmol/ in blood
L), it the results are shown in Table 2.
Table 2
| 0h | 0.5h | 1h | 2h | 4h | 6h | 8h | 10h | 12h | 24h | |
| Embodiment 1 | 4.3 | 3.4 | 3.0 | 2.6 | 2.6 | 2.6 | 2.6 | 2.6 | 2.6 | 2.9 |
| Embodiment 2 | 4.4 | 3.5 | 3.2 | 2.8 | 2.8 | 2.9 | 3.2 | 3.2 | 3.2 | 3.5 |
| Embodiment 3 | 4.3 | 3.5 | 3.1 | 2.9 | 2.9 | 2.9 | 3.1 | 3.3 | 3.3 | 3.6 |
As can be seen from Table 2, dry suspensoid agent of the invention has good slow release effect, can realize hyperphospheremia in for 24 hours
Phosphorus concentration maintains more stable level in rat blood, and the combination of suspending agent selection sodium alginate and povidone relative to
For individual suspending agent, slow release effect is more preferable.
The present invention is described in detail above, its object is to allow the personage for being familiar with this field technology that can understand this
The content of invention is simultaneously implemented, and it is not intended to limit the scope of the present invention, and the present invention is not limited to above-mentioned implementations
, equivalent change or modification made by all Spirit Essences according to the present invention should be covered by the protection scope of the present invention.
Claims (10)
1. a kind of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent, it is characterised in that：By weight comprising the following raw material component：Carbonic acid
100 parts of sevelamer, 400-600 parts of filler, 50-70 parts of suspending agent, 10-20 parts of corrigent.
2. 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent according to claim 1, it is characterised in that：By weight comprising such as
Lower raw material components：100 parts of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, 500 parts of filler, 60 parts of suspending agent, 15 parts of corrigent.
3. 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent according to claim 1 or 2, it is characterised in that：The filler is selected from sugarcane
One or more of sugar, lactose, mannitol, starch, xylitol, maltitol.
4. 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent according to claim 1 or 2, it is characterised in that：The suspending agent is selected from carboxylic
One or more of sodium carboxymethylcellulose pyce, sodium alginate, povidone.
5. 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent according to claim 4, it is characterised in that：The suspending agent is sodium alginate
With the composition of povidone, and the mass ratio of the two be 1 ~ 3:1.
6. 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent according to claim 5, it is characterised in that：The sodium alginate and described poly-
The mass ratio for tieing up ketone is 2:1.
7. 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent according to claim 1 or 2, it is characterised in that：The corrigent be selected from Ah
One or more of this Ba Tian, fragrant citrus essence, trisodium citrate.
8. 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent according to claim 7, it is characterised in that：The corrigent is A Siba
Sweet tea, fragrant citrus essence, trisodium citrate are 1 ~ 3 by weight:0.5~1.5:The mixture of 1 composition.
9. 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent according to claim 8, it is characterised in that：The Aspartame, the perfume (or spice)
Orange essence, the trisodium citrate weight ratio be 2:1:1.
10. a kind of preparation method of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent as claimed in any one of claims 1-9 wherein, feature
It is：Include the following steps：
（1）2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate is sieved with 100 mesh sieve, filler, suspending agent and corrigent are crossed to 80 mesh sieve respectively；
（2）By 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate, filler, suspending agent and the corrigent after sieving, adds water and be uniformly mixed, prepare softwood；
The sieve granulation of 25 mesh, 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate dry suspensoid agent is obtained after dry.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810683078.6A CN108743546B (en) | 2018-06-28 | 2018-06-28 | Sevelamer carbonate dry suspension and preparation method thereof |
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| CN201810683078.6A CN108743546B (en) | 2018-06-28 | 2018-06-28 | Sevelamer carbonate dry suspension and preparation method thereof |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104800165A (en) * | 2015-04-22 | 2015-07-29 | 青岛正大海尔制药有限公司 | Sevelamer carbonate dry suspension agent and preparation method thereof |
| EP2773329B1 (en) * | 2011-11-04 | 2016-01-13 | Synthon BV | Pharmaceutical compositions comprising sevelamer |
| CN107375218A (en) * | 2017-08-24 | 2017-11-24 | 青岛正大海尔制药有限公司 | A kind of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate oral sustained-release dry suspension |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2773329B1 (en) * | 2011-11-04 | 2016-01-13 | Synthon BV | Pharmaceutical compositions comprising sevelamer |
| CN104800165A (en) * | 2015-04-22 | 2015-07-29 | 青岛正大海尔制药有限公司 | Sevelamer carbonate dry suspension agent and preparation method thereof |
| CN107375218A (en) * | 2017-08-24 | 2017-11-24 | 青岛正大海尔制药有限公司 | A kind of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate oral sustained-release dry suspension |
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Address after: 215212 No. 6 Jinzi Road, Lili Town, Wujiang District, Suzhou City, Jiangsu Province Applicant after: Suzhou Shengda Pharmaceutical Co., Ltd. Applicant after: Suzhou third pharmaceutical factory Co., Ltd. Address before: 215212 No. 9 Jiaotong East Road, Lili Town, Wujiang District, Suzhou City, Jiangsu Province Applicant before: China Union Chempharma (Suzhou) Co., Ltd. Applicant before: Suzhou third pharmaceutical factory Co., Ltd. |
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