CN101579325B - Metformin hydrochloride controlled-release tablet and preparation method thereof - Google Patents
Metformin hydrochloride controlled-release tablet and preparation method thereof Download PDFInfo
- Publication number
- CN101579325B CN101579325B CN2009101040999A CN200910104099A CN101579325B CN 101579325 B CN101579325 B CN 101579325B CN 2009101040999 A CN2009101040999 A CN 2009101040999A CN 200910104099 A CN200910104099 A CN 200910104099A CN 101579325 B CN101579325 B CN 101579325B
- Authority
- CN
- China
- Prior art keywords
- release
- metformin hydrochloride
- release tablet
- tablet
- coating
- 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.)
- Active
Links
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a metformin hydrochloride controlled-release tablet, which comprises a metformin hydrochloride controlled-release tablet with effective dose and pharmaceutical accessories and is characterized in that the metformin hydrochloride controlled-release tablet uses the common tabletting, and the controlled-release effect is controlled by totally depending on the film coating technique. The coating adopted by the invention is a releasing system comprising the prescription which can cause the medicine to reach release degree standard in vitro. The preparation method in the invention is simple and convenient; the process conditions are easy to control and suitable for batch production, can use conventional production equipment in pharmaceutical industries for economically andconveniently producing the metformin hydrochloride controlled-release tablet on a large scale, can effectively and stably cause the release degree of the metformin hydrochloride controlled-release ta blet in the second hour to be 10% to 35%, the release degree to be 40% to 70% in the sixth hour and the release degree to be more than 80% in the twelfth hour.
Description
Technical field
The present invention relates to a kind of diabecron sustained-release tablet that is applicable to the single type ii diabetes that can not effectively control with diet and exercise therapy of treatment and preparation method thereof.
Background technology
Diabetes have become " No. three killer " that threaten the mankind after tumor and cardiovascular and cerebrovascular disease as a kind of serious non-infectious chronic disease.No matter in developed country or developing country, its sickness rate is all in rapid rising.It is estimated that about 2.46 hundred million people in the whole world suffered from diabetes in 2007,46% is 40～59 years old labour force's population, if do not take any measure, expects 2025, and whole world diabetics will be increased to 3.8 hundred million, wherein 80% concentrate on middle and low income country.China is nearly more than 2,000 ten thousand diabeticss at present, and the trend that increases is year by year arranged, and other has impaired glucose tolerance person nearly 2,000 ten thousand; Another part correlation study shows that present Chinese diabetics number has occupied the second place of the world, more will reach 5,930 ten thousand people when estimating 2025.2006, diabetes occupied the tenth of the Chinese inpatient cause of disease, the 6th of urbanite's cause of death, and for this reason, researching and developing safely and effectively, antidiabetic medicine has become the task of top priority.
Diabecron sustained-release tablet (Metformin Hydrochloride Sustained-release Tablets) has the blood glucose toleration that improves the type 2 diabetes mellitus patient as a kind of blood sugar lowering, reduces the effect of basis and post-prandial glycemia.The mechanism of action of metformin hydrochloride is different from the oral hypoglycemic of other type, it can reduce the generation of glycogen, reduce the absorption of small intestinal to glucose, and can be by increasing the sensitivity that insulin improves to the picked-up and the utilization of glucose in peripheral tissues, different with sulfonylureas is that metformin hydrochloride can not produce hypoglycemia to the patient of type 2 diabetes mellitus patient or euglycemia.After the metformin hydrochloride treatment, secretion of insulin remains unchanged, and reduce the fasting insulin level and every day plasma insulin level.
At present, diabecron sustained-release tablet is a kind of antidiabetic drug of can be oral and being used widely, and its clinical efficacy and safety constantly are confirmed.Because its effect is definite, can control and can prevent, give that diabetics, especially concomitant fertilizer are fat, plasma insulin is higher, the Secondary cases sulphanylureas lost efficacy and the patient's of type i diabetes insulinize poor blood glucose control treatment has brought bigger Gospel.Now, existing this class slow releasing preparation listing, also there are a plurality of slow release methods to obtain patent, as (1) patent No. 200310112200.8, its technology summary is that metformin hydrochloride, hydroxypropyl methylcellulose, the filler of recipe quantity are pressed dried particles after the common process granulation, oven dry, granulate, granulate of tablet, add micropowder ethyl cellulose, lubricant mixing after tabletting promptly.(2) patent No. 02138478.9, its technology summary is by behind the abundant mixing of equivalent incremental method with recipe quantity metformin hydrochloride, excipient (HPMC, MC, EC etc.), add an amount of alcoholic solution, make soft material, granulation, oven dry, use tabletting behind the adding lubricant mixing.(3) patent No. 02133574.5, and its technology summary is to adopt unique slow release method, utilizes high viscosity macromolecular material (HPMC, PVP, acroleic acid resin etc.) imbibition to form gel, makes the slow releasing tablet that only need use every day once.(4) patent No. 200410022155.1, its technology summary is for sieving metformin hydrochloride, polyvinylpyrrolidone, pregelatinized Starch after according to the recipe quantity mix homogeneously, add 6% hydroxypropyl emthylcellulose system soft material again, granulation, oven dry, granulate, tabletting behind the adding magnesium stearate mixing, reuse enteric coating powder coating gets final product.(5) patent No. 200610167664.2, and its technology summary is pressed into double-layer sustained release tablets or coated tablet after metformin hydrochloride dative row agent spy is made granule with HPMC, EC, PVP etc. respectively, and main feature is that it is a compound sustained-released product.Also have some and (5) the similar patent of compound product, but these patents all are to rely on the excipient of label or label excipient to add the coating sustained controlling and the purpose that reaches final slow release.There is following problem in these preparations by the skeleton slow release: 1. release inequality has the prominent phenomenon of releasing or do not release; 2. sheet is great, and in the above-mentioned patent, when the main constituent metformin hydrochloride was 500mg, sheet is heavy generally all to be 800mg～1000mg.3. in the preparation process, framework material viscosity is big, and cleaning is difficult.4. the release in vitro degree is low, and the matrix sustained release tablet release in vitro time generally can not reach more than 12 hours or 12 hours, and its final release value is 70%～75%.
Summary of the invention
The object of the present invention is to provide a kind of diabecron sustained-release tablet that reaches the delivery system of slow release by coating.The gentle effectively blood sugar lowering of this slow releasing preparation energy slowly discharges medicine in vivo, keeps steady plasma-drug concentration, improves the safety of drug use, can reduce again and take number of times (getting final product once a day), raising patient's compliance.
Another object of the present invention is to provide a kind of preparation method that can be suitable for the diabecron sustained-release tablet industrial-scale production.
The object of the present invention is achieved like this: a kind of diabecron sustained-release tablet, it comprises the metformin hydrochloride of effective dose and the adjuvant on the pharmaceutics, it is characterized in that: described diabecron sustained-release tablet is the delivery system that reaches slow release by coating; Its coating material adopts one or more in the following component: hydroxypropyl cellulose, ethyl cellulose, methylcellulose, acroleic acid resin, propylene glycol, hexadecanol, octadecanol, Polyethylene Glycol, polyvidone, polyvinyl alcohol, polyvinylpyrrolidone.
Above-mentioned coating material comprises base material and other components; Base material is an ethyl cellulose, other components be in hydroxypropyl cellulose, methylcellulose, acroleic acid resin, propylene glycol, hexadecanol, octadecanol, Polyethylene Glycol, polyvinyl alcohol, polyvidone, the polyvinylpyrrolidone any or several; Its proportion relation is an ethyl cellulose: other components=1: 0.3～0.8, and in weight portion.
Above-mentioned coating material adopt pure soluble solvent dissolve coating solution; Metformin hydrochloride raw material in the described slow releasing tablet: coating solution=1: 0.04～0.5, preferred proportion is 1: 0.1～0.35, in weight portion.
Pure soluble solvent is 95% ethanol in the above-mentioned coating solution; 95% amount of alcohol added is in the base material in the coating material, and coating solution concentration is 3～5%, by weight percentage.
The coating material of above-mentioned slow releasing tablet is by as the ethyl cellulose of base material, make coating solution as hexadecanol 95% dissolve with ethanol of plasticizer; Plasticizer wherein: porogen=0.5～0.8: 1.Or propylene glycol, adopt as the Polyethylene Glycol of porogen or polyvidone
In the above-mentioned slow releasing tablet supplementary product consumption by weight, metformin hydrochloride: adjuvant=1: 0.1～0.35.
Filler in the slow releasing agent of the present invention, lubricant and binding agent, the consumption of each component by weight, filler is 0.01～0.1, lubricant 0.001～0.03 and binding agent 0.01～0.1.Preferred filler is 0.04～0.08, and lubricant is 0.009～0.022 and binding agent 0.03～0.085.Filler, lubricant and binding agent say with respect to principal agent, measures all fewerly, if decide like this in order to reduce the heavy increase of sheet, thereby increases the compliance that the patient uses; And add these adjuvants in right amount are homogeneity of passing through the coatings release for the smooth and easy and principal agent of label manufacturing process.
Adjuvant on the described pharmaceutics in the slow releasing agent of the present invention is filler, lubricant and binding agent; Wherein filler is selected one or more in the following adjuvant for use: starch, gelatin, lactose, dextrin, microcrystalline Cellulose, pregelatinized Starch; Lubricant is selected one or more in the following adjuvant for use: micropowder silica gel, Pulvis Talci, stearic acid and its esters; Binding agent is selected one or more in the following adjuvant for use: water, 75% ethanol or sodium carboxymethyl cellulose.
Another object of the present invention is achieved in that a kind of preparation method of diabecron sustained-release tablet, it is characterized in that: adopt the film packaging technique to make slow releasing tablet again the metformin hydrochloride and the elder generation of the adjuvant on the pharmaceutics tabletting of effective dose.
Specifically, at first with the filler in metformin hydrochloride raw material and the adjuvant, binding agent pulverize separately, cross 120 mesh sieves; Elder generation adds metformin hydrochloride raw material and filler in the wet granulator, after high-speed stirred is even, adds binding agent, continues stirring and evenly mixing, makes soft material, granulation then, dry, granulate, and adding lubricant tabletting gets plain sheet; Plain sheet is crossed 100～200 mesh sieves with coating solution after the assay was approved, begins whitewashing after plain sheet is preheated to 35 ℃～40 ℃, flow set was at 200～300ml/ minute, control rotating speed and inlet temperature, leaving air temp are whitewashed under the situation of plain sheet non-stick pan, the dry finished product that gets.
The film baking temperature was 40 ℃～70 ℃ when coating finished; Described rotating speed is 4～6 rev/mins, 50 ℃～70 ℃ of inlet temperature, 40 ℃～50 ℃ of leaving air temps.
Slow releasing preparation provided by the invention mainly is a delivery system that can make the coated formula composition of medicament slow release, and its slow release effect mainly relies on the film packaging technique to reach.The used adjuvant of the preparation process of the label of slow releasing tablet of the present invention be full conventional tablet commonly used and can reach the slow release purpose without any one, rely on art for coating to reach release in vitro scale standard fully.This film coating material mainly utilizes widely used coating base material to add plasticizer, porogen and solvent and makes, and mainly makes it reach release in vitro scale standard by control process parameters then.Control under the stable situation in process conditions, the quality of each batch product energy basically identical can satisfy modern large-scale commercial production preferably.If (as sudden outage, die etc.) arranged at technological parameter under the situation of unexpected variation, can also the processing or/and the process conditions scale of carrying out is done over again by former prescription, the product after the processing is satisfying the requirement that still can reach the release in vitro degree under the condition of technology.In the test of its release in vitro degree of slow releasing preparation of the present invention metformin hydrochloride when release was the 10%～35%, 6th hour in the 2nd hour release be that 40%～70% and the 12nd hour release is more than 80%.The diabecron sustained-release tablet specification that the present invention makes is 500mg, and every coating tablets sheet sheet heavily is 560mg～580mg, and it is minimum to increase weight.
Diabecron sustained-release tablet of the present invention, the supplementary material in its tablet is all common to be easy to get, good and cheap.Used equipment all is preparation pharmaceutical factory conventional equipments in its preparation process, and its production capacity is big, and production cost is low, and cleans conveniently the yield height.In a word, the preparation method among the present invention is easy, process conditions are easy to control, be suitable for producing in batches, and with the conventional equipment in the pharmaceuticals industry can be in enormous quantities, economy implements to produce easily, and can be when abnormal conditions occurring, carry out the batch processing of doing over again.
The specific embodiment
Further specify the present invention below in conjunction with embodiment, but the present invention is not limited to these embodiment.
Embodiment: a kind of diabecron sustained-release tablet, its preparation method is: at first with metformin hydrochloride raw material and filler, binding agent pulverize separately, cross 120 mesh sieves; By the equivalent principle of progressively increasing, earlier metformin hydrochloride raw material and filler are added in the wet granulator, high-speed stirred evenly after, add binding agent, continue stirring and evenly mixing, make soft material, granulate then, dry, granulate, adding lubricant tabletting gets plain sheet; Plain sheet after the assay was approved, coating solution is crossed 100～200 mesh sieves, begin whitewashing after plain sheet is preheated to 40 ℃～50 ℃, flow set was at 200～300ml/ minute, control 4～6 rev/mins of rotating speeds, 50 ℃～60 ℃ of inlet temperature, 40 ℃～50 ℃ of leaving air temps well, under the situation of plain sheet non-stick pan, whitewashing, the dry finished product that gets.
Example 1: the weight portion proportioning of each component sees Table 1:
Table 1
Preparation process: according to said ratio: at first with metformin hydrochloride, amylum pregelatinisatum, lactose pulverize separately, cross 120 mesh sieves, take by weighing by recipe quantity respectively, standby; After getting ethyl cellulose and an amount of 95% ethanol (cold preservation is spent the night), supply 95% ethanol by said ratio and make into 5% coating solution, standby;
Get amylum pregelatinisatum, be mixed with 7% farinaceous size, standby;
Get metformin hydrochloride, lactose powder,, make soft material with 7% farinaceous size by the equivalent principle mix homogeneously that progressively increases.
Granulate with 14 mesh sieves, in 55～60 ℃ of dryings, the control water content is less than 3%.
Behind 16 mesh sieve granulate, add the magnesium stearate of recipe quantity, mixing, tabletting, controlled pressure is 7～8kg/cm2 during tabletting.
After the plain sheet passed examination, open the coating machine, tablet is inserted wherein, regulate flow 200～250ml/ branch, 4～6 rev/mins of rotating speeds, 50 ℃～60 ℃ of inlet temperature, 40 ℃～50 ℃ of leaving air temps and the about 4kpa of spray gun pressure under the not bonding situation of plain sheet, spraying (flow-control was at 200ml/ minute) continuously, coating finishes back (increasing weight about 4%), and discharging gets final product.
Drug release determination situation such as following table 2:
Table 2
Example 2: the weight portion proportioning of each component sees Table 3:
Table 3
Preparation process: according to said ratio: at first metformin hydrochloride, amylum pregelatinisatum, gelatin are pulverized, crossed 120 mesh sieves, take by weighing by recipe quantity respectively, standby; After getting ethyl cellulose and an amount of 95% ethanol (cold preservation is spent the night), supply 95% ethanol by said ratio and make into 5% coating solution, standby;
Get metformin hydrochloride, gelatin powder, amylum pregelatinisatum is made soft material by the equivalent principle mix homogeneously that progressively increases with an amount of purified water.
Granulate with 14 mesh sieves, in 55～60 ℃ of dryings, the control water content is less than 3%.
Behind 16 mesh sieve granulate, add the Pulvis Talci of recipe quantity, mixing, tabletting, controlled pressure is 7～8kg/cm2 during tabletting.
After the plain sheet passed examination, open the coating machine, tablet is inserted wherein, regulate flow, rotating speed, go out/inlet air temperature and spray gun pressure, under the not bonding situation of plain sheet, sprayed (flow-control was at 200ml/ minute) continuously, coating finishes back (increasing weight about 4%), and discharging gets final product.
Drug release determination situation such as following table 4:
Table 4
Example 3: the weight portion proportioning of each component sees Table 5:
Table 5
Preparation process: according to said ratio: at first metformin hydrochloride and microcrystalline Cellulose are pulverized, crossed 120 mesh sieves, take by weighing by recipe quantity respectively, standby; After getting ethyl cellulose and 95% ethanol (cold preservation is spent the night), make 5% coating solution by said ratio, standby;
Get metformin hydrochloride, microcrystalline Cellulose by the equivalent principle mix homogeneously that progressively increases, make soft material with an amount of hyprolose aqueous solution.
Granulate with 14 mesh sieves, in 55～60 ℃ of dryings, the control water content is less than 3%.
Behind 16 mesh sieve granulate, add the magnesium stearate of recipe quantity, mixing, tabletting, controlled pressure is 7～8kg/cm2 during tabletting.
After the plain sheet passed examination, open the coating machine, tablet is inserted wherein, regulate flow, rotating speed, go out/inlet air temperature and spray gun pressure, under the not bonding situation of plain sheet, sprayed (flow-control was at 200ml/ minute) continuously, coating finishes back (increasing weight about 4%), and discharging gets final product.
Drug release determination situation such as following table 6:
Table 6
Example 4: the weight portion proportioning of each component sees Table 7:
Table 7
Preparation process: according to said ratio: at first, go out behind the part film, pulverized 120 mesh sieves again diabecron sustained-release tablet (material of doing over again) crushing screening, standby; Get metformin hydrochloride, dextrin, the pregelatinized Starch of recipe quantity, pulverize, cross 120 mesh sieves, take by weighing by recipe quantity respectively, standby; After getting ethyl cellulose and 95% ethanol (needing cold preservation to spend the night), make 5% coating solution by said ratio, standby;
Get metformin hydrochloride and do over again material and virgin material, dextrin and pregelatinized Starch, make soft material with suitable quantity of water by the equivalent principle mix homogeneously that progressively increases.
Granulate with 14 mesh sieves, in 55～60 ℃ of dryings, the control water content is less than 3%.
Behind 16 mesh sieve granulate, add the micropowder silica gel of recipe quantity, mixing, tabletting, controlled pressure is 7～8kg/cm during tabletting
2
After the plain sheet passed examination, open the coating machine, tablet is inserted wherein, regulate flow, rotating speed, go out/inlet air temperature and spray gun pressure, under the not bonding situation of plain sheet, sprayed (flow-control was at 200ml/ minute) continuously, coating finishes back (increasing weight about 3%), and discharging gets final product.
Drug release determination situation such as following table 8:
Table 8
The selection example of table 9 diabecron sustained-release tablet adjuvant and sustained-release matrix
Its release in vitro degree of diabecron sustained-release tablet that table 10 prepares by last table
Drug release determination method and standard that the present invention adopts:
Get this product, according to drug release determination method (two appendix X of Chinese Pharmacopoeia version in 2005 D, first method), adopt dissolution method first subtraction unit, phosphate buffer 1 000ml with pH6.8 is a release medium, and rotating speed is that per minute 100 changes, operation in accordance with the law, through 2 hours, 6 hours and 12 hours, get solution 10ml respectively, filter, and the instant phosphate buffer 1 0ml that in stripping rotor, replenishes the pH6.8 of uniform temp; Precision is measured each 1ml of subsequent filtrate respectively, puts in the 100ml measuring bottle, is diluted with water to scale, shakes up, and according to ultraviolet visible spectrophotometry (two appendix IV of Chinese Pharmacopoeia version in 2005 A), measures absorbance at the wavelength place of 233nm, presses C
4H
11N
5Absorptance (the E of HCl
1cm 100%) be 798 to calculate every burst size at different time.Every of this product should be respectively more than 10%～35%, 40%～70% and 80% of labelled amount in the burst size of 2 hours, 6 hours and 12 hours, all should be up to specification.
From the release in vitro degree testing result of above example as can be known: this production technology easy operating, enforcement and stable are fit to the large-scale production of GMP workshop, if any emergency case (as the outage etc.) processing of that it(?) also can scale when occurring causing product to do over again do over again.The good product quality that this explained hereafter goes out, the bright and clean perfection of outward appearance can reach accurate and other the every quality index of release in vitro scale and increase weight lessly, is easy to the patient and accepts.
Claims (8)
1. diabecron sustained-release tablet, it comprises the metformin hydrochloride of effective dose and the adjuvant on the pharmaceutics, it is characterized in that: described diabecron sustained-release tablet is the delivery system that reaches slow release by coating; The coating material of described slow releasing tablet is by as the ethyl cellulose of base material, as the hexadecanol of plasticizer or propylene glycol, adopt 95% dissolve with ethanol to make coating solution as the Polyethylene Glycol or the polyvidone of porogen, 95% amount of alcohol added is in the base material in the coating material, coating solution concentration is 3～5%, by weight percentage; Plasticizer wherein: porogen=0.5～0.8: 1; Adjuvant on the described pharmaceutics is filler, lubricant and binding agent, the consumption of wherein said each component by weight, filler is 0.04～0.08, lubricant is 0.009～0.022, binding agent 0.03～0.085.
2. diabecron sustained-release tablet as claimed in claim 1 is characterized in that: the base material in the described coating material: other components=1: 0.3～0.8, and in weight portion.
3. diabecron sustained-release tablet as claimed in claim 2 is characterized in that: coating material adopt pure soluble solvent dissolve coating solution; Metformin hydrochloride raw material in the described slow releasing tablet: coating solution=1: 0.04～0.5, in weight portion.
4. diabecron sustained-release tablet as claimed in claim 2 is characterized in that: in the described slow releasing tablet supplementary product consumption by weight, metformin hydrochloride: adjuvant=1: 0.1～0.35.
5. as the arbitrary described diabecron sustained-release tablet of claim 1～4, it is characterized in that: described filler is selected one or more in the following adjuvant for use: starch, sodium carboxymethyl cellulose, gelatin, lactose, dextrin, microcrystalline Cellulose; Described lubricant is selected one or more in the following adjuvant for use: micropowder silica gel, Pulvis Talci, stearic acid and its esters; Described binding agent is selected one or more in the following adjuvant for use: water, 75% ethanol or sodium carboxymethyl cellulose.
6. as the preparation method of the arbitrary described diabecron sustained-release tablet of claim 1～5, it is characterized in that: adopt the film packaging technique to make slow releasing tablet again the metformin hydrochloride and the elder generation of the adjuvant on the pharmaceutics tabletting of effective dose.
7. the preparation method of diabecron sustained-release tablet as claimed in claim 6 is characterized in that: at first with the filler in metformin hydrochloride raw material and the adjuvant, binding agent pulverize separately, cross 120 mesh sieves; Elder generation adds metformin hydrochloride raw material and filler in the wet granulator, after high-speed stirred is even, adds binding agent, continues stirring and evenly mixing, makes soft material, granulation then, dry, granulate, and adding lubricant tabletting gets plain sheet; Plain sheet is crossed 100～200 mesh sieves with coating solution after the assay was approved, begins whitewashing after plain sheet is preheated to 35 ℃～40 ℃, flow set was at 200～300ml/ minute, control rotating speed and inlet temperature, leaving air temp are whitewashed under the situation of plain sheet non-stick pan, the dry finished product that gets.
8. the preparation method of diabecron sustained-release tablet as claimed in claim 7 is characterized in that: the film baking temperature was 40 ℃～70 ℃ when coating finished; Described rotating speed is 4～6 rev/mins, 50 ℃～70 ℃ of inlet temperature, 40 ℃～50 ℃ of leaving air temps.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101040999A CN101579325B (en) | 2009-06-16 | 2009-06-16 | Metformin hydrochloride controlled-release tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101040999A CN101579325B (en) | 2009-06-16 | 2009-06-16 | Metformin hydrochloride controlled-release tablet and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101579325A CN101579325A (en) | 2009-11-18 |
| CN101579325B true CN101579325B (en) | 2011-05-25 |
Family
ID=41361733
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009101040999A Active CN101579325B (en) | 2009-06-16 | 2009-06-16 | Metformin hydrochloride controlled-release tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101579325B (en) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102440975B (en) * | 2011-11-22 | 2013-11-13 | 浙江万马药业有限公司 | Metformin hydrochloride sustained-release tablets and preparation method thereof |
| CN103622930B (en) * | 2013-12-19 | 2015-06-10 | 石家庄市华新药业有限责任公司 | Metformin hydrochloride slow release preparation and preparation method thereof |
| CN106074425A (en) * | 2016-06-23 | 2016-11-09 | 南京华宽信息咨询中心 | A kind of hypoglycemic diabecron sustained-release tablet and preparation method thereof |
| CN106723341B (en) * | 2017-03-16 | 2020-04-14 | 云南巴菰生物科技有限公司 | Fragrance sustained-release material composition, sustained-release perfume colloid and application thereof |
| CN107049980A (en) * | 2017-04-01 | 2017-08-18 | 重庆康刻尔制药有限公司 | A kind of diabecron sustained-release tablet and preparation method thereof |
| CN107412182B (en) * | 2017-04-01 | 2020-11-13 | 重庆康刻尔制药股份有限公司 | Preparation method of metformin hydrochloride sustained-release tablets |
| CN108969501A (en) * | 2018-08-20 | 2018-12-11 | 奕利制药有限公司 | A kind of Metformin hydrochloride intragastric floating tablets and preparation method thereof |
| CN111249244A (en) * | 2020-03-06 | 2020-06-09 | 重庆康刻尔制药有限公司 | Gliclazide controlled release tablet and preparation method thereof |
| CN111450069A (en) * | 2020-04-02 | 2020-07-28 | 南京致中生物科技有限公司 | Metformin hydrochloride oral sustained-release tablet and preparation method thereof |
| CN112336739B (en) * | 2020-05-27 | 2022-03-22 | 广东赛康药业有限公司 | Pharmaceutical composition of metformin hydrochloride and mecobalamin and preparation method thereof |
| CN111821868A (en) * | 2020-06-17 | 2020-10-27 | 武汉工程大学 | Ethyl cellulose composite membrane and preparation method and application thereof |
| CN112999182B (en) * | 2020-08-19 | 2023-04-07 | 重庆康刻尔制药股份有限公司 | Metformin hydrochloride dual sustained and controlled release composition and preparation method and application thereof |
| CN112972411B (en) * | 2021-04-09 | 2022-05-31 | 迪沙药业集团有限公司 | Metformin hydrochloride sustained-release tablet composition |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1589782A (en) * | 2003-08-28 | 2005-03-09 | 安徽省新药研究院 | Dimethyl biguanidine hydrochloride slow release particle and its preparation method |
-
2009
- 2009-06-16 CN CN2009101040999A patent/CN101579325B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1589782A (en) * | 2003-08-28 | 2005-03-09 | 安徽省新药研究院 | Dimethyl biguanidine hydrochloride slow release particle and its preparation method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101579325A (en) | 2009-11-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101579325B (en) | Metformin hydrochloride controlled-release tablet and preparation method thereof | |
| CN101785763B (en) | Metformin hydrochloride enteric-coated sustained release tablet and preparation method thereof | |
| CN101057849A (en) | Slow-releasing preparation containing metformin hydrochloride and glipizide and its preparation method | |
| CN101375849B (en) | Novel dosage form of sinomenine medicament or hydrochlorate thereof and preparation technique thereof | |
| CN103479592B (en) | Metformin hydrochloride sustained release tablets and preparation method thereof | |
| CN103301084A (en) | Berberine hydrochloride tablet and preparation method thereof | |
| CN106727404A (en) | Diabecron sustained-release tablet and preparation method thereof | |
| CN111588701B (en) | Metformin hydrochloride sustained release tablet and preparation method thereof | |
| CN101810628B (en) | Melbine glipizide tablet and preparation method thereof | |
| CN105582008A (en) | Composition containing vildagliptin and metformin and preparation method of composition | |
| CN106924237B (en) | It is a kind of containing En Gelie is net and the pharmaceutical composition of Metformin hydrochloride | |
| CN110141555A (en) | A kind of net piece of En Gelie and preparation method thereof | |
| CN101167731A (en) | Dispersible tablet containing metformin and glibenclamide and preparation method thereof | |
| CN110585155A (en) | Gliclazide tablet (II) and preparation method thereof | |
| CN109010298B (en) | Metformin and glipizide compound composition and preparation method thereof | |
| CN1331470C (en) | Method for preparing high stripping-degree hautriwaic glipizide capsule | |
| CN103565774A (en) | Glipizide controlled release composition as well as preparation method thereof | |
| CN103127022A (en) | Allopurinol composite type drug release system and preparation method of allopurinol | |
| CN111228357A (en) | Chaiyin micro-pill preparation and preparation method thereof | |
| CN107441051B (en) | Propafenone hydrochloride micro-tablet and preparation method thereof | |
| CN109646417A (en) | A kind of Trimetazidine sustained release tablets and preparation method thereof | |
| CN103385862B (en) | A kind of metoprolol tartrate extended release tablets and preparation method thereof | |
| CN101278919B (en) | Metformin hydrochloride and Glipizide sustained-release pellet and method of preparing the same | |
| CN111450069A (en) | Metformin hydrochloride oral sustained-release tablet and preparation method thereof | |
| CN101721414B (en) | Composition containing pioglitazone hydrochloride and metformin hydrochloride and preparation 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 | ||
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: North District 401122 Chongqing City No. 101 garden Jinyu Road Patentee after: Chongqing kangkere Pharmaceutical Co., Ltd Address before: North District 401122 Chongqing City No. 101 garden Jinyu Road Patentee before: CHONGQING CONQUER PHARMACEUTICAL Co.,Ltd. |