CN104856970B - A kind of vildagliptin tablet for treating type II diabetes - Google Patents
A kind of vildagliptin tablet for treating type II diabetes Download PDFInfo
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- CN104856970B CN104856970B CN201510349305.8A CN201510349305A CN104856970B CN 104856970 B CN104856970 B CN 104856970B CN 201510349305 A CN201510349305 A CN 201510349305A CN 104856970 B CN104856970 B CN 104856970B
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- vildagliptin
- tablet
- supplementary material
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- gluconic acid
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Abstract
The invention belongs to pharmaceutical preparations technology field, disclose a kind of vildagliptin tablet for treating type II diabetes, the tablet be after supplementary material is mixed direct tablet compressing and obtain, described supplementary material includes vildagliptin, gluconic acid, disintegrant and lubricant.Present invention vildagliptin contained by during preparation and storage is substantially without degraded, steady quality；Preparation method uses direct compression method, and technique is simple and easy to control, it is easy to industrialized production.
Description
Technical field
The invention belongs to technical field of medicine, in particular to a kind of solid orally ingestible of high stability, especially
It is related to a kind of tablet containing vildagliptin and preparation method thereof.
Background technology
Glucose-dependent-insulinotropic polypeptide (GIP) and glucagon kind polypeptide-1 (GLP-1) are to maintain internal Portugal
The important hormone of grape sugar concentration, is all acted on incretin.Patients with NIDDM GIP promoting insulin secretion by
Damage, only GLP-l can play insulinotropic hormone secretion, it promotes pancreas islet by acting on the acceptor on B cell film
The secretion of element.GLP-1 may also suppress the secretion of hyperglycemic factor and suppress gastric emptying to increase satiety (appetite-suppressing).
DPP-IV is present in many tissues with protein binding, such as kidney, liver, brush edge, ductus pancreaticus, lymphocyte, the endothelium of small goldbeater's skin
Cell, it can inactivate it rapidly by hydrolyzing GLP-1 the 2nd alanine of N-terminal, so as to reach the mesh for the treatment of type II diabetes
's.
Vildagliptin is a kind of with selective, competitive, reversible DPP-IV inhibitor, can quickly be suppressed after administration
DPP-4 activity, making empty stomach and after the meal endogenous blood glucose element GLP-1 (hyperglycemic factor polypeptide -1) and GIP, (glucose dependency promotees
Insulin polypeptides) level rise, and then increase beta cell to the sensitiveness of glucose, promote glucose dependent insulin
Secretion.By increasing endogenous GLP-1 levels, vildagliptin can also increase sensitiveness of the α cells to glucose, make glucose
The secretory volume compatible degree of level and hyperglycemic factor is improved.During hyperglycaemia, vildagliptin is by raising duodenin water
It is flat, increase the ratio of insulin/hyperglycemic factor, cause to reduce with liver glucose growing amount after the meal on an empty stomach, and then reduce blood
Sugar.Chemical entitled 1- [[(3- hydroxy-l-adamantyls) amino] the acetyl group] -2- cyano group-(5)-tetrahydro pyrrolidine of the medicine,
Structural formula is as follows：
Vildagliptin is to damp and hot extremely unstable, therefore in the production process of its preparation, how straight using dry granulations or dry powder
The technique of pressure, but it is serious still to be degraded after long term storage, causes drug quality to decline.
CN101618216B discloses a kind of by DPP IV (DPP-IV) inhibitor (i.e. vildagliptin) compound
Tablet, its preparation method and pharmaceutical formulation that direct tablet compressing is formed.But its magnesium stearate lubricant used with activity into
The raw coordination of distribution makes active component occur degradation reaction, including cyclization, hydrolysis etc., causes its stability in preparation or storage
Reduction.CN104161752 A lubricants select sodium stearyl fumarate, and technique is direct tablet compressing, to delay drug hydrolysis, but should
Preparation adds the purchase cost of material and the production cost of medicine using the other lubricants being of little use.
The content of the invention
In view of the deficiencies in the prior art, it is an object of the invention to provide a kind of production cost is low, steady quality Wei Ge
Arrange spit of fland tablet.
In order to realize the purpose of the present invention, inventor carries out screening study by lot of experiments to auxiliary material, it has unexpectedly been found that
The hydrolysis that gluconic acid can suppress vildagliptin occurs, it is particularly possible to suppresses magnesium stearate and occurs with vildagliptin caused by being coordinated
Degradation reaction, so as to increase substantially the stability of preparation.
Specifically, the purpose of the present invention is achieved by the following technical solution：A kind of dimension for treating type II diabetes
Ge Lieting tablets, the tablet be after supplementary material is mixed direct tablet compressing and obtain, described supplementary material includes vildagliptin, glucose
Acid, disintegrant and lubricant.
Preferably, vildagliptin tablet as described above, supplementary material therein can also include filler, filler plus
Enter to be more beneficial for the compressing of tablet.
In embodiment preferred for this invention, vildagliptin tablet as described above, supplementary material therein is by Wei Gelie
Spit of fland, gluconic acid, filler, disintegrant and lubricant composition.
It is further preferred that vildagliptin tablet as described above, the weight ratio of vildagliptin and gluconic acid therein
For 1：(0.4~3.0).Still further preferably, the weight ratio of vildagliptin and gluconic acid therein is 1：(0.8~1.5).
Vildagliptin tablet of the present invention, described disintegrant is selected from PVPP, sodium carboxymethyl starch, low taken
For the one or more in hydroxypropyl cellulose and Ac-Di-Sol.It is fine that described filler is selected from lactose, crystallite
Tie up the one or more in element, mannitol, dextrin, sucrose and pregelatinized starch.Described lubricant is selected from magnesium stearate, tristearin
One or more in furmaric acid sodium and talcum powder.
Present invention also offers the preparation method of above-mentioned vildagliptin tablet, this method comprises the following steps：By Wei Gelie
Spit of fland is sieved, and is added gluconic acid, microcrystalline cellulose, sodium carboxymethyl starch and is well mixed, add lubricant, is well mixed, directly
Tabletting is formed.
Compared with prior art, vildagliptin tablet of the present invention and preparation method thereof has the following advantages that and significantly
Progressive：(1) preparation vildagliptin contained by during preparation and storage is substantially without degraded, steady quality；(2) in preparation prescription
Cost can be used lower and magnesium stearate lubricant more often, while being conducive to quality control；
(3) preparation method is simple, it is easy to industrialized production.
Embodiment
The preparation process and implementation result of the present invention, but the protection of the present invention are now further described by following examples
Scope is not limited to following examples.
Embodiment 1
Preparation method：
Vildagliptin is crossed into 100 mesh sieves, gluconic acid, microcrystalline cellulose, the carboxymethyl shallow lake that recipe quantity crosses 80 mesh sieves is added
Powder sodium is well mixed, and adds magnesium stearate, is well mixed, direct tablet compressing is formed.
Embodiment 2
Preparation method：
Vildagliptin is crossed into 100 mesh sieves, the poly- dimension of gluconic acid, microcrystalline cellulose, crosslinking that recipe quantity crosses 100 mesh sieves is added
Ketone is well mixed, and adds magnesium stearate, is well mixed, direct tablet compressing is formed.
Embodiment 3
Preparation method：
Vildagliptin is crossed into 80 mesh sieves, the poly- dimension of gluconic acid, microcrystalline cellulose, crosslinking that recipe quantity crosses 100 mesh sieves is added
Ketone is well mixed, and adds magnesium stearate, is well mixed, direct tablet compressing is formed.
Comparative example 1
Preparation method：
Vildagliptin is crossed into 80 mesh sieves, recipe quantity is added and crosses the microcrystalline cellulose of 100 mesh sieves, PVPP mixing
It is even, magnesium stearate is added, is well mixed, tabletting is formed.
Comparative example 2
Preparation method：
Vildagliptin is crossed into 80 mesh sieves, citric acid, microcrystalline cellulose, PVPP that recipe quantity crosses 100 mesh sieves is added
It is well mixed, magnesium stearate is added, is well mixed, tabletting is formed.
Embodiment 4：The relevant agent detection test of vildagliptin piece before and after accelerated test
Each 6 of vildagliptin tablet prepared by Example 1-3 and comparative example 1-2 puts 100ml measuring bottles respectively as sample
In, plus appropriate diluent, shaking dissolves vildagliptin, is diluted to scale with diluent, shakes up, and filters, takes subsequent filtrate conduct
Need testing solution.Take vildagliptin reference substance appropriate, it is accurately weighed, dissolved and diluted with diluent and be made in every 1ml containing about 2.5
μ g solution is used as reference substance solution.Determined according to high performance liquid chromatography (two D of annex V of Chinese Pharmacopoeia version in 2010), with ten
Eight alkyl silane bonded silica gels are filler；0.02mol/L sodium dihydrogen phosphates (two hypophosphite monohydrate sodium dihydrogen 3.12g are taken, plus
Water 1000ml makes dissolving, plus triethylamine 1ml, mixes, with phosphorus acid for adjusting pH value to 2.8)-acetonitrile (96:4) it is mobile phase A,
0.02mol/L sodium dihydrogen phosphates-acetonitrile (75:25) it is Mobile phase B；According to the form below carries out gradient elution, and flow velocity is per minute
1.0ml, Detection wavelength is 210nm, and column temperature is 35 DEG C.
The μ l of system suitability solution 20 are taken, liquid chromatograph is injected, chromatogram is recorded, precision measures need testing solution and right
According to each 20 μ l of product solution, liquid chromatograph is injected separately into, chromatogram is recorded.Single impurity must not cross 0.2%.Record and calculate each
Content average of the group sample about material.
Table 1：Each embodiment measurement result
It was found from from the test statistics result of table 1, vildagliptin piece prepared by 1-3 of the embodiment of the present invention, accelerated investigation
Afterwards, relevant material is basically unchanged；And gluconic acid is not added in the auxiliary material of comparative example 1, relevant material increase is obvious；Comparative example 2
Gluconic acid is replaced using citric acid, effect is more bad.
Claims (7)
1. a kind of vildagliptin tablet for treating type II diabetes, the tablet be after supplementary material is mixed direct tablet compressing and obtain, its
It is characterised by, described supplementary material includes vildagliptin, gluconic acid, disintegrant and lubricant, vildagliptin and gluconic acid
Weight ratio be 1：（0.4~3.0）.
2. vildagliptin tablet according to claim 1, it is characterised in that described supplementary material also includes filler.
3. vildagliptin tablet according to claim 1, it is characterised in that described supplementary material is by vildagliptin, grape
Saccharic acid, filler, disintegrant and lubricant composition.
4. vildagliptin tablet according to claim 1, it is characterised in that the weight ratio of vildagliptin and gluconic acid is
1：（0.8~1.5）.
5. vildagliptin tablet according to claim 1, it is characterised in that described disintegrant be selected from PVPP,
One or more in sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose and Ac-Di-Sol.
6. vildagliptin tablet according to claim 2, it is characterised in that it is fine that described filler is selected from lactose, crystallite
Tie up the one or more in element, mannitol, dextrin, sucrose and pregelatinized starch.
7. vildagliptin tablet according to claim 1, it is characterised in that described lubricant is selected from magnesium stearate, hard
One or more in resin acid fumaric acid sodium and talcum powder.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510349305.8A CN104856970B (en) | 2015-06-23 | 2015-06-23 | A kind of vildagliptin tablet for treating type II diabetes |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510349305.8A CN104856970B (en) | 2015-06-23 | 2015-06-23 | A kind of vildagliptin tablet for treating type II diabetes |
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| Publication Number | Publication Date |
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| CN104856970A CN104856970A (en) | 2015-08-26 |
| CN104856970B true CN104856970B (en) | 2017-08-25 |
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| CN201510349305.8A Expired - Fee Related CN104856970B (en) | 2015-06-23 | 2015-06-23 | A kind of vildagliptin tablet for treating type II diabetes |
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Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105193752B (en) * | 2015-10-27 | 2018-03-30 | 石家庄康贺威药业有限公司 | A kind of vildagliptin tablet and preparation method thereof |
| CN107998089A (en) * | 2017-12-28 | 2018-05-08 | 广东伊茗药业有限公司 | A kind of vildagliptin tablet for treating type II diabetes |
| CN110051685A (en) * | 2019-03-13 | 2019-07-26 | 安庆瑄宇医药科技有限公司 | A kind of vildagliptin hypoglycemic chewable tablets and preparation method thereof |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101618216B (en) * | 2004-01-20 | 2012-01-04 | 诺瓦提斯公司 | Direct compression formulation and process |
| CN101106977A (en) * | 2005-01-18 | 2008-01-16 | 诺瓦提斯公司 | Direct compression formulation and process |
| CN101287495A (en) * | 2005-06-10 | 2008-10-15 | 诺瓦提斯公司 | Direct compression formulation of DPP-IV inhibitors and glitazones, and process |
| MX2010009731A (en) * | 2008-03-04 | 2010-09-30 | Merck Sharp & Dohme | Pharmaceutical compositions of a combination of metformin and a dipeptidyl peptidase-iv inhibitor. |
| PE20091730A1 (en) * | 2008-04-03 | 2009-12-10 | Boehringer Ingelheim Int | FORMULATIONS INVOLVING A DPP4 INHIBITOR |
| KR20120003906A (en) * | 2009-03-27 | 2012-01-11 | 교린 세이야꾸 가부시키 가이샤 | Matrix-type sustained release preparation containing basic additive |
| KR20130137624A (en) * | 2010-09-03 | 2013-12-17 | 브리스톨-마이어스 스큅 컴퍼니 | Drug formulations using water soluble antioxidants |
| AR085689A1 (en) * | 2011-03-07 | 2013-10-23 | Boehringer Ingelheim Int | PHARMACEUTICAL COMPOSITIONS OF METFORMIN, LINAGLIPTINE AND AN SGLT-2 INHIBITOR |
| US9555001B2 (en) * | 2012-03-07 | 2017-01-31 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition and uses thereof |
| WO2014193528A1 (en) * | 2013-04-29 | 2014-12-04 | Anovel Pharmaceuticals, Llc | Amorphous dosage forms and methods |
| CN104161752B (en) * | 2013-05-16 | 2018-09-07 | 江苏豪森药业集团有限公司 | A kind of vildagliptin composition |
| CN103877043A (en) * | 2014-03-18 | 2014-06-25 | 薛娟 | Sitgliptin phosphate dispersible tablet and preparation method thereof |
| CN103893142A (en) * | 2014-03-18 | 2014-07-02 | 薛娟 | Onglyza dispersible tablet and preparation method thereof |
| CN103933031B (en) * | 2014-05-13 | 2017-01-18 | 中国药科大学 | Compound preparation including DPP-4 inhibitor and metformin hydrochloride and preparation method thereof |
| CN103976997B (en) * | 2014-05-13 | 2016-08-17 | 中国药科大学 | A kind of blood sugar lowering compound sustained release capsules and preparation method thereof |
| CN104324033A (en) * | 2014-11-20 | 2015-02-04 | 哈尔滨圣吉药业股份有限公司 | Sitagliptin and dimethyldiguanide sustained release tablets and preparation method thereof |
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| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information |
Inventor after: Zhang Lei Inventor after: Gu Yan Inventor after: Zhu Yamei Inventor after: Wang Na Inventor after: Chen Shufang Inventor before: Sun Lihua |
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| CB03 | Change of inventor or designer information | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20170727 Address after: 266035 Department of Endocrinology, Qingdao endocrine Diabetes Hospital, 760 Hefei Road, Shandong, Qingdao, China Applicant after: Zhang Lei Address before: 211224, Herb biology, 8 industrial town crystal Town, Lishui District, Jiangsu, Nanjing Applicant before: Sun Lihua |
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