CN1985819A - Slow released preparation containing metformin hydrochloride and gliclazide and its preparing process - Google Patents
Slow released preparation containing metformin hydrochloride and gliclazide and its preparing process Download PDFInfo
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- CN1985819A CN1985819A CN 200610167664 CN200610167664A CN1985819A CN 1985819 A CN1985819 A CN 1985819A CN 200610167664 CN200610167664 CN 200610167664 CN 200610167664 A CN200610167664 A CN 200610167664A CN 1985819 A CN1985819 A CN 1985819A
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- gliclazide
- metformin hydrochloride
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Abstract
The present invention relates to a kind of slow released preparation containing metformin hydrochloride and glicazide and its preparation process. The preparation consists of slow released metformin hydrochloride and slow released glicazide. The metformin hydrochloride is released in 15-40 % in the first 1 hr, 50-70 % in the first 4 hr, and over 75 % in the first 8 hr; and the glicazide is released in 20-40 % in the first 2 hr, 40-65 % in the first 4 hr and over 75 % in the first 10 hr. The slow released preparation containing metformin hydrochloride and glicazide has mild and lasting blood sugar reduction, capacity of avoiding hypoglycemia, gastrointestinal discomfort and other untoward reaction, decreased medicine taking times and raised compliance. The present invention also discloses the extracorporeal slow releasing characteristic and preparation process of the slow released preparation.
Description
Technical field
The present invention relates to a kind of compound preparation that combines by two kinds of antidiabetic drug gliclazide and metformin hydrochloride, be used for the treatment of and rely on diet control and temper compound slow release preparation of the effective type ii diabetes of blood sugar control and preparation method thereof.
Background technology
This compound recipe system is made up of two kinds of hypoglycemic medicines, but its mechanism of action difference.Both complement each other.
Metformin hydrochloride does not promote insulin secretion, and its blood sugar reducing function is mainly and promotes the fatty tissue ingestion of glucose, and muscular tissue anerobic glycolysis is increased, and increases the utilization of glucose, can also reduce glucose through gastral absorption.
Gliclazide is a second filial generation sulphanylureas oral hypoglycemic thing, and its mechanism is optionally to act on beta Cell of islet, and the secretion of promotion endogenous insulin, and the insulin release behind the raising feed glucose are suppressed glycogen generation and output.The people is effective to maturity-onset diabetes.Can reduce platelet adhesion power, reduce plasma viscosity, cholesterol reducing is accumulated, and reduces the plasma concentration of aorta triphosphoric acid glyceride and fatty acid.
At present, the listing of this compound preparation has been arranged, but only be common delivery formulations, and this compound preparation is taken frequently, taking dose is big, occurs a series of untoward reaction easily, as hypoglycemia, serious gastrointestinal reaction etc.The invention provides and a kind ofly pass row together specially for the compound slow release preparation of active component by metformin hydrochloride, the compound preparation of being formed only need be taken once and get final product every day.
At present, having had by metformin hydrochloride and passed row together specially for the ordinary preparation patent of active component, only is ordinary preparation still.Do not see the pertinent literature and the patent report of relevant compound metformin hydrochloride Gliclazide delayed-release preparation.
Summary of the invention
Technology described in the invention relates to field of medicaments, is meant that specifically with metformin hydrochloride, gliclazide be slow releasing preparation of active component and preparation method thereof.The gentle effectively blood sugar lowering of this compound preparation energy reduces adverse reaction rate (hypoglycemia, gastrointestinal upset etc.), and medicine is slowly discharged in vivo, keep the blood drug level of stable state, improve the safety of drug use, can reduce again and take number of times (getting final product once a day), improve patient's compliance.
Slow releasing preparation described in the invention, the amount that each preparation unit contains the active component gliclazide is 7.5-90mg, is preferably 15-60mg, the amount that contains the active ingredient hydrochloric acid metformin is 125-750mg.Be preferably 250-500mg.Both preferred compound doses are gliclazide 15mg, metformin hydrochloride 250mg and gliclazide 30mg, metformin hydrochloride 500mg.
Slow releasing preparation described in the invention partly is made up of the dual-sustained-release of metformin hydrochloride and two kinds of medicines of gliclazide.Wherein:
The diabecron sustained-release part, metformin hydrochloride discharged 15-40% on the 1st hour in the dissolution in vitro test, discharged 50-70%, discharged more than 75% on the 8th hour in the 4th hour.
The Gliclazide delayed-release part discharged 20-40% on the 2nd hour in the dissolution in vitro test, discharged 40-65%, discharged more than 75% on the 10th hour in the 4th hour.
Metformin hydrochloride and gliclazide slow releasing preparation of the present invention, the extracorporeal releasing characteristic of its medicine can obtain by the coating that carries out that the coated formula of sustained-release matrix or slow release is formed.Also can get by above two kinds of technological means use in conjunction.
Sustained-release matrix of the present invention, comprise hydroxypropyl methylcellulose HPMC-4M, HPMC-15M, HPMC-100M, one of polyvinylpyrrolidone, ethyl cellulose, hydroxyethyl-cellulose, hexadecanol, octadecanol, Rikemal B 200, stearic acid, glyceryl monostearate, Brazil wax, sodium carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, chitin or they optional two or more.
In the sustained release coating of the present invention prescription, slow-release material commonly used comprises ethyl cellulose and aqueous dispersion thereof, stearic acid, cellulose acetate, crylic acid resin (as RS100, RL100, RS30D, RL30D, NE30D) one of them or several mixture.In the sustained release coating prescription, can also add some porogen, antiplastering aid, plasticizer etc. in case of necessity.Plasticizer can be propylene glycol, Polyethylene Glycol, triethyl citrate, dimethyl phthalate (ethyl ester, butyl ester) etc.; Porogen can be Polyethylene Glycol, polyvidone, sucrose, salt, HPMC etc.; Antiplastering aid can be Pulvis Talci, Kaolin etc.
The specific embodiment
Come compound metformin hydrochloride Gliclazide delayed-release preparation of the present invention and preparation method thereof done further specifying by following example, but be not limited in following example.
Embodiment 1 metformin hydrochloride and gliclazide double-layer sustained release tablets
Prescription:
| Metformin hydrochloride HPMC-15M microcrystalline Cellulose | 500g 150g 30g |
| Gliclazide | 5g |
| HPMC-100M EC calcium hydrogen phosphate 80% alcoholic solution Pulvis Talci is made altogether | An amount of 1000 of 30g 1.5g 105g |
Preparation method:
Metformin hydrochloride is crossed 100 mesh sieves, and HPMC-15M, microcrystalline Cellulose are crossed 60 mesh sieves, and with 80% alcoholic solution system soft material, 16 mesh sieves are granulated behind the supplementary material mix homogeneously, 40 ℃ of dryings, and 16 mesh sieve granulate add the Pulvis Talci mix homogeneously, and are standby; In addition gliclazide is sieved with HPMC-4M, lactose, microcrystalline Cellulose and mix three times, with 80% alcoholic solution system soft material, 16 mesh sieves are granulated, 60 ℃ of dryings, 16 mesh sieve granulate.Take by weighing above two kinds of granules respectively in proportion, successively tabletting is made double-layer sustained release tablets.
Embodiment 2 compound metformin hydrochloride gliclazide film-coat slow releasing tablet
Prescription:
| Metformin hydrochloride | 250g |
| Gliclazide | 15g |
| HPMC-K100M | 5g |
| Microcrystalline Cellulose Pulvis Talci 2%PVP-k30 alcoholic solution Aquacoat is made altogether | An amount of 1000 of 350g 4g |
Preparation method:
Metformin hydrochloride, gliclazide are crossed 100 mesh sieves, standby; Get metformin hydrochloride, with equivalent (250g) microcrystalline Cellulose mix homogeneously, with 2%PVP-k30 alcoholic solution system soft material, 20 mesh sieves are granulated, drying, 18 mesh sieve granulate; Other gets gliclazide, and microcrystalline Cellulose, HPMC-K100 mix homogeneously with surplus are prepared into granule with method; Get two kinds of granule mix homogeneously tablettings.After plain sheet carries out general galenic pharmacy passed examination, open the coating pelletizing machine, tablet is inserted wherein.Regulate wind pressure, temperature, adjustment rotary speed, start peristaltic pump, spray into the Aquacoat coating solution, coating finishes back (increasing weight about 12%), and discharging gets final product.
Embodiment 3 compound metformin hydrochloride Gliclazide delayed-release pellet capsules
Prescription:
| Metformin hydrochloride | 250g |
| Gliclazide HPMC-K100 Rikemal B 200 | 15g 80g 15g |
| Microcrystalline Cellulose 70% alcoholic solution is made altogether | An amount of 1000 of 45g |
Preparation method:
Metformin hydrochloride, gliclazide are crossed 100 mesh sieves, HPMC-K100, microcrystalline Cellulose, Rikemal B 200 are crossed 60 mesh sieves, behind the supplementary material mix homogeneously, add the wet soft material of 70% alcoholic solution system, 12-20 order aperture is extruded into the bar, the bottom rotary speed that are about 3-5cm and is adjusted to 600-1200rpm, round as a ball about 5 minutes, get final product, drying fills in micropill in No. 2 conventional capsule shells, promptly gets above-mentioned slow releasing capsule.
Embodiment 4 compound metformin hydrochloride Gliclazide delayed-release coated micropill capsules
Prescription:
| Metformin hydrochloride | 250g |
| Gliclazide microcrystalline Cellulose purified water is made altogether | An amount of 1000 of 15g 150g |
Sustained release coating liquid composition
| Cellulose acetate | 50g |
| Acrylic resin S100 sodium chloride dimethyl phthalate Pulvis Talci | 1g 2g 2.5g 15g |
| Ethanol | Add to 1000ml |
Preparation method:
Metformin hydrochloride, gliclazide are crossed 100 mesh sieves, and microcrystalline Cellulose is crossed 60 mesh sieves, and is standby; Get metformin hydrochloride, behind 120g microcrystalline Cellulose mix homogeneously, add the wet soft material of an amount of system of purified water, 14-20 order aperture is extruded into the bar, the bottom rotary speed that are about 3-5cm and is adjusted to 800-1000rpm, and round as a ball about 3-5 minute, get final product, drying, standby; Get gliclazide and surplus microcrystalline Cellulose mix homogeneously, be prepared into the pastille micropill with method; Other gets recipe quantity cellulose acetate etc. and joins in the ethanol, stirs to make it dissolving, add other adjuvant after, stir, standby; Get metformin hydrochloride pastille micropill, place the coating fluid bed, regulate air intake pressure 0.3-0.7bar, temperature 30-50 ℃, adjust rotary speed 100-200rpm, start peristaltic pump, spray into the coating solution for preparing and carry out coating, weightening finish is controlled at 15-20%; Get gliclazide medicine carrying micropill with method, carry out coating with method, the coating weightening finish is controlled at 20-30%, and after coating finished, about 2h was merged in 40 ℃ of insulations, gets final product; Getting above medicine carrying coated micropill fills in the examples of suitable shell, promptly according to certain mixed.
Embodiment 5 compound metformin hydrochloride Gliclazide delayed-release granule capsules
Prescription:
The diabecron sustained-release granule
| Metformin hydrochloride calcium hydrogen phosphate HPMC-K100 EC 60% alcoholic solution | 250g 20g 80g 20g 30g |
| The Gliclazide delayed-release granule | |
| Gliclazide | 15g |
| Calcium hydrogen phosphate HPMC-K100 EC 60% alcoholic solution | 5g 30g 5g 30g |
Preparation method:
Metformin hydrochloride is crossed 100 mesh sieves, and other adjuvant is crossed 60 mesh sieves, and mix homogeneously, is crossed 24 mesh sieves and granulated as binding agent moistening and stirring with 60% alcoholic solution, in 50 ℃ of dry 2-3 hours, and 20 mesh sieve granulate, standby; Get gliclazide and each adjuvant mix homogeneously is prepared into slow-releasing granules with method, two kinds of granules are mix homogeneously proportionally, gets final product in incapsulating.
Embodiment 6 embodiment effect explanations
The mensuration of the external stripping curve of the embodiment of the invention 1 preparation:
The preparation of the present invention such as embodiment 1 preparation is measured according to the method for the relevant requirements of the Pharmacopoeia of the People's Republic of China 2005 editions.
Experimental condition is as follows:
Dissolution test system: ZRS-8G intelligence dissolution test instrument (unlimited power plant of University Of Tianjin)
Rotating speed: 70rpm
Dissolution medium: pH6.8 phosphate buffer (simulated intestinal fluid)
Stripping volume: 900ml
Measurement result is as follows:
Preparation metformin hydrochloride stripping result among table one: the embodiment 1
| Sample time (h) | 1 | 4 | 8 |
| Actual stripping percent (%) | 19.6±1.1 | 58.2±0.8 | 80.1±0.9 |
| Expectation stripping percent (%) | 15-40 | 50-70 | ＞75 |
Preparation gliclazide stripping result among table two: the embodiment 1
| Sample time (h) | 2 | 4 | 10 |
| Actual stripping percent (%) | 27.6±1.7 | 52.4±1.3 | 88.6±0.7 |
| Expectation stripping percent (%) | 20-40 | 40-65 | ＞75 |
The result shows: the actual result of extraction of two kinds of medicines in the preparation, be consistent with expected value, and prescription and technology in the present embodiment are described, can reach the effect that delays drug release.
Claims (9)
1. a slow releasing preparation that contains metformin hydrochloride and gliclazide is characterized in that, this slow releasing preparation is that two slow-released parts are formed.
2. the slow releasing preparation of claim 1, the amount that described each preparation unit contains the active component gliclazide is 7.5-90mg, is preferably 15-60mg, the amount that contains the active ingredient hydrochloric acid metformin is 125-750mg.Be preferably 250-500mg.Both preferred compound doses are gliclazide 15mg, metformin hydrochloride 250mg and gliclazide 30mg, metformin hydrochloride 500mg.
3. the slow releasing preparation of claim 1, described diabecron sustained-release part is characterized in that metformin hydrochloride discharged 15-40% on the 1st hour in the dissolution in vitro test, discharges 50-70%, discharges more than 75% on the 8th hour in the 4th hour.
4. the slow releasing preparation of claim 1, described Gliclazide delayed-release part is characterized in that gliclazide discharged 20-40% on the 2nd hour in the dissolution in vitro test, discharged 40-65%, discharged more than 75% on the 10th hour on the 4th hour.
5. the described slow releasing preparation of claim 1-4 is characterized in that, can be tablet, granule, slow-release pill, slow releasing capsule.
6. the described slow releasing preparation of claim 1-4 is characterized in that comprising the delivery system that the coated formula of medicament slow release is formed by a sustained-release matrix or.Also can be both use in conjunction.
7. the described sustained-release matrix of claim 6, it is characterized in that, comprise hydroxypropyl methylcellulose HPMC-4M, HPMC-15M, HPMC-100M, one of polyvinylpyrrolidone, ethyl cellulose, hydroxyethyl-cellulose, hexadecanol, octadecanol, Rikemal B 200, stearic acid, glyceryl monostearate, Brazil wax, sodium carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, chitin or they optional two or more.
8. the main slow releasing agent in the described coated formula of claim 6, it is characterized in that, comprise ethyl cellulose and aqueous dispersion thereof, methylcellulose, cellulose acetate, crylic acid resin (as RS100, RL100, RS30D, RL30D, NE30D) one of them or several mixture.
9. the described slow releasing preparation of claim 1-4 is characterized in that can be used for the treatment of type ii diabetes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610167664 CN1985819A (en) | 2006-11-21 | 2006-12-21 | Slow released preparation containing metformin hydrochloride and gliclazide and its preparing process |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200610114676.9 | 2006-11-21 | ||
| CN200610114676 | 2006-11-21 | ||
| CN 200610167664 CN1985819A (en) | 2006-11-21 | 2006-12-21 | Slow released preparation containing metformin hydrochloride and gliclazide and its preparing process |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1985819A true CN1985819A (en) | 2007-06-27 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610167664 Pending CN1985819A (en) | 2006-11-21 | 2006-12-21 | Slow released preparation containing metformin hydrochloride and gliclazide and its preparing process |
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| CN (1) | CN1985819A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009098195A1 (en) * | 2008-02-05 | 2009-08-13 | Valpharma S.A. | Oral pharmaceutical formulations containing gliclazide |
| CN101843617A (en) * | 2010-03-05 | 2010-09-29 | 中国药科大学 | Slow release preparation of compound Repaglinide-metformin hydrochloride |
| CN104546778A (en) * | 2014-12-25 | 2015-04-29 | 北京华禧联合科技发展有限公司 | Medical composition of Gliclazide sustained release preparation and preparation method of medical composition |
-
2006
- 2006-12-21 CN CN 200610167664 patent/CN1985819A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009098195A1 (en) * | 2008-02-05 | 2009-08-13 | Valpharma S.A. | Oral pharmaceutical formulations containing gliclazide |
| CN101843617A (en) * | 2010-03-05 | 2010-09-29 | 中国药科大学 | Slow release preparation of compound Repaglinide-metformin hydrochloride |
| CN104546778A (en) * | 2014-12-25 | 2015-04-29 | 北京华禧联合科技发展有限公司 | Medical composition of Gliclazide sustained release preparation and preparation method of medical composition |
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| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20070627 |