CN112336739A - Pharmaceutical composition of metformin hydrochloride and mecobalamin and preparation method thereof - Google Patents
Pharmaceutical composition of metformin hydrochloride and mecobalamin and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition of metformin hydrochloride and mecobalamin and a preparation method thereof. The pharmaceutical composition of the invention is a blunt-release ordinary tablet, which comprises the following components in parts by weight: 250-1000 parts of metformin hydrochloride, 0.05-1.1 parts of mecobalamin, 30-300 parts of adhesive, 2-200 parts of blunt release regulator and 1-10 parts of lubricant. The pharmaceutical composition of metformin hydrochloride and mecobalamin can effectively solve the problem of vitamin B12 deficiency in human bodies when metformin hydrochloride is applied, and simultaneously, the release of the drugs is slowed down by regulating and controlling the release rate of metformin hydrochloride, so that the gastrointestinal adverse reactions of metformin hydrochloride preparations are reduced.
Description
The application is a divisional application with application number 202010463154.X, application date 2020, 5/27 and the name of 'a pharmaceutical composition of metformin hydrochloride and mecobalamin and a preparation method thereof'.
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition of metformin hydrochloride and mecobalamin and a preparation method thereof.
Background
Diabetes is a global public health problem, and Diabetic Peripheral Neuropathy (DPN) is one of common chronic complications of diabetes, has high morbidity, is a high-risk factor causing diabetic foot ulcer and lower limb amputation, and is a main cause of disability and death of diabetic patients. Metformin hydrochloride is a first-line drug for patients with known type 2 diabetes, and when the metformin hydrochloride is applied for a long time, the absorption of vitamin B12 by the patients is affected, so that the vitamin B12 in the patients is reduced. Vitamin B12 is an essential element for structural and functional integrity of the nervous system, and thus may cause or aggravate diabetic peripheral neuropathy. Therefore, for the diabetic patient treated by the metformin hydrochloride, the vitamin B12 is systemically supplemented, and the Diabetic Peripheral Neuropathy (DPN) can be prevented or treated, so that the metformin hydrochloride injection has very important significance.
At present, metformin hydrochloride has good treatment effect on obesity and diabetes as a diabetes drug, can be used independently, can also be used together with sulfonylureas or insulin, and has wide clinical application. However, metformin is rapidly absorbed, the action time is only 2-4 hours, and the metformin is required to be taken 2-3 times per day, so that the fluctuation of blood concentration in a body is large, gastrointestinal adverse reactions are easily caused, and diabetic peripheral neuropathy is easily caused or aggravated. Chinese patent application CN103239424A discloses a metformin hydrochloride sustained-release pellet capsule, which consists of a metformin hydrochloride capsule core, a pellet coating and an enteric capsule shell, wherein the excipient of the capsule core is one or more of microcrystalline cellulose, lactose, xylitol, mannitol and water, and the sustained-release coating is prepared by adopting acrylic resin macromolecules, talcum powder and the like. The invention combines the advantages of the sustained release technology and the enteric technology by utilizing the capsule preparation, thereby solving the technical problems of larger tablet weight and sustained release. However, the metformin hydrochloride preparation of the invention has complex process, and is not in line with the positioning of metformin on the basic medication of diabetes. Meanwhile, long-term application can lead to the reduction of vitamin B12 in patients, and cause or aggravate Diabetic Peripheral Neuropathy (DPN).
Therefore, how to improve the application of metformin hydrochloride, slow down the gastrointestinal adverse reaction of metformin hydrochloride, and solve the problems of vitamin B12 deficiency in human bodies and the like in the application of metformin hydrochloride becomes a problem to be solved urgently at present.
Disclosure of Invention
The invention aims at providing a pharmaceutical composition of metformin hydrochloride and mecobalamin and a preparation method thereof, the pharmaceutical composition of metformin hydrochloride and mecobalamin can effectively solve the problem of vitamin B12 deficiency in human bodies when metformin hydrochloride is applied, and meanwhile, in order to reduce adverse reactions of gastrointestinal tracts of metformin hydrochloride bodies, a metformin hydrochloride sustained-release tablet and a metformin hydrochloride double-layer double-release tablet can be slowly released within 12 h; compared with the commercially available metformin hydrochloride ordinary tablet, the dull-release ordinary tablet can delay release for 15-60 minutes, so that the effect of alleviating gastrointestinal adverse reactions is achieved.
A pharmaceutical composition of metformin hydrochloride and mecobalamin comprises the following components in parts by weight:
250-1000 parts of metformin hydrochloride;
0.05-1.1 parts of mecobalamin;
5-350 parts of a binder;
30-800 parts of a slow-release framework material;
2-200 parts of a slow-release regulator;
20-400 parts of a filler;
2-20 parts of a lubricant;
0-15 parts of a flow aid;
1-80 parts of a shading coating agent.
Further, the pharmaceutical composition is a sustained-release tablet, a double-layer double-release tablet or a blunt-release ordinary tablet.
Further, the sustained release tablet comprises the following components in parts by weight: 250-1000 parts of metformin hydrochloride, 0.05-1.1 parts of mecobalamin, 30-300 parts of an adhesive, 30-800 parts of a slow-release framework material and 1-10 parts of a lubricant.
Further, the metformin hydrochloride layer of the double-layer double-release tablet comprises the following components in parts by weight: 250-1000 parts of metformin hydrochloride, 30-300 parts of adhesive, 30-800 parts of slow-release framework material and 1-10 parts of lubricant; the mecobalamin layer of the double-layer double-release tablet comprises the following components in parts by weight: 0.05-1.1 parts of mecobalamin, 5-50 parts of an adhesive, 20-400 parts of a filler, 1-10 parts of a lubricant and 0-15 parts of a flow aid.
Further, the blunt-release common tablet comprises the following components in parts by weight: 250-1000 parts of metformin hydrochloride, 0.05-1.1 parts of mecobalamin, 30-300 parts of adhesive, 2-200 parts of blunt release regulator and 1-10 parts of lubricant.
Further, the adhesive comprises one or more of ethylene-vinyl acetate copolymer, polylactic acid-glycolic acid copolymer, copovidone, povidone, polyoxyethylene, polyvinyl alcohol, sodium carboxymethyl cellulose, hydroxypropyl cellulose, ethyl cellulose and hydroxyethyl cellulose.
Further, the sustained-release framework materials of the sustained-release tablet and the double-layer double-release tablet comprise one or more of polyoxyethylene, hydroxypropyl cellulose, hydroxyethyl cellulose and hydroxypropyl methylcellulose.
Further, the viscosity of the hypromellose is 100000 mpa.s.
Still further, the hydroxyethylcellulose has a viscosity of 160000 mpa.s.
Further, the slow-release regulator comprises one or more of methacrylic acid-ethyl acrylate copolymer, ethyl acrylate-methyl methacrylate copolymer, quaternary ammonium methacrylate copolymer, ethyl cellulose, octadecanol, magnesium stearate and glyceryl behenate.
Further, the filler is microcrystalline cellulose PH102 or corn starch.
Further, the lubricant is magnesium stearate or/and stearic acid.
Further, the glidant is one or more of colloidal silicon dioxide, silicon dioxide or talcum powder.
Further, the light-shielding coating agent is a light-shielding coating agent containing dark iron oxide colored pastilles.
Further, the slow-release regulator comprises one or more of methacrylic acid-ethyl acrylate copolymer, ethyl acrylate-methyl methacrylate copolymer, quaternary ammonium methacrylate copolymer, ethyl cellulose, octadecanol, magnesium stearate and glyceryl behenate.
The invention provides a preparation method of a metformin hydrochloride and mecobalamin pharmaceutical composition sustained-release tablet, which comprises the following steps:
s1) preparing metformin hydrochloride sustained-release granules: carrying out wet granulation, hot-melt extrusion granulation or fluidized bed one-step granulation on metformin hydrochloride, mecobalamin and an adhesive, and then uniformly mixing the mixture with a sustained-release framework material to prepare metformin hydrochloride sustained-release granules;
s2) uniformly mixing the metformin hydrochloride sustained-release granules obtained in the step S1 with a lubricant, and tabletting on a tabletting machine to obtain sustained-release tablets;
s3) coating the sustained-release tablet of step S2 with a light-shielding coating agent.
The invention provides a preparation method of a metformin hydrochloride and mecobalamin pharmaceutical composition double-layer double-release tablet, which comprises the following steps:
s1) preparing metformin hydrochloride sustained-release granules: the metformin hydrochloride and the adhesive are granulated by a wet method, hot-melt extrusion granulation or fluidized bed one-step granulation, and then are uniformly mixed with the slow-release framework material and the lubricant to prepare the metformin hydrochloride slow-release granules;
s2) preparing mecobalamin mixed powder: sieving and mixing mecobalamin, adhesive, filler, glidant and lubricant;
s3) pressing the metformin hydrochloride sustained-release granules obtained in the step S1 and the mecobalamin mixed powder obtained in the step S2 on a double-layer tablet press to obtain double-layer double-release tablets;
s4) coating the bilayer dual release tablet or the sustained release tablet of step S3 with a light-shielding coating agent.
Further, the preparation method of the metformin hydrochloride sustained-release granule by wet granulation comprises the following steps: mixing metformin hydrochloride and a binding agent according to the formula amount, adding purified water for wet granulation to prepare metformin hydrochloride wet granules, drying, finishing granules, and mixing with a sustained-release framework material and a lubricant to obtain the metformin hydrochloride sustained-release granules.
Further, the preparation method of the metformin hydrochloride sustained-release granule hot-melt extrusion granulation comprises the following steps: mixing metformin hydrochloride and a binding agent according to the formula amount to obtain a physical mixture; and adding the physical mixture into a double-screw extruder, extruding in a strip shape, cooling, crushing, sieving, and mixing with the slow-release framework material and the lubricant to obtain the metformin hydrochloride slow-release granules.
Further, the preparation method of the metformin hydrochloride sustained-release granules by one-step granulation comprises the following steps: putting the metformin hydrochloride with the formula ratio into a fluidized bed granulator, spraying the aqueous solution of the adhesive to perform fluidized bed granulation, drying, finishing granules, and mixing with the slow-release framework material and the lubricant to obtain the metformin hydrochloride slow-release granules.
The invention also provides a preparation method of the metformin hydrochloride and mecobalamin pharmaceutical composition slow-release ordinary tablet, which comprises the following steps:
s1) preparing metformin hydrochloride, mecobalamin composition granules: carrying out wet granulation, hot-melt extrusion granulation or fluidized bed one-step granulation on metformin hydrochloride, mecobalamin, an adhesive and a slow-release regulator to obtain metformin hydrochloride and mecobalamin composition granules;
s2) uniformly mixing the metformin hydrochloride and mecobalamin composition granules obtained in the step S1 and the lubricant, and tabletting on a tabletting machine to obtain a tablet core of an ordinary tablet with blunt release;
s3) coating the tablet core of the blunt-release conventional tablet of step S2 with a light-shielding coating agent.
Further, the preparation method of the metformin hydrochloride and mecobalamin composition granules by wet granulation comprises the following steps: mixing metformin hydrochloride, a binding agent and a slow-release regulator according to the formula amount, adding a mecobalamin solution for wet granulation, preparing wet granules, drying, finishing granules, and mixing with a lubricant to obtain the metformin hydrochloride and mecobalamin combined granule.
Further, the preparation method of the metformin hydrochloride and mecobalamin composition granules by hot melt extrusion granulation comprises the following steps: mixing metformin hydrochloride, adhesive and blunt release regulator according to the formula ratio to obtain a physical mixture; and adding the physical mixture into a double-screw extruder, extruding in a strip shape, cooling, crushing, sieving, and mixing with mecobalamin and a lubricant to obtain the metformin hydrochloride and mecobalamin composition granules.
Further, the preparation method of the metformin hydrochloride and mecobalamin composition granules by one-step granulation comprises the following steps: putting the metformin hydrochloride with the formula ratio into a fluidized bed granulator, spraying aqueous solution of mecobalamin, adhesive and slow-release regulator to carry out fluidized bed granulation, drying, granulating, and mixing with lubricant to obtain the metformin hydrochloride and mecobalamin composition granules.
In the invention, the metformin hydrochloride is a medicament very soluble in water, and the inventor prepares metformin hydrochloride sustained-release granules by adopting wet granulation, hot-melt extrusion granulation or one-step granulation through a large number of creative experiments, and prepares the metformin hydrochloride sustained-release granules into sustained-release tablets and double-layer double-release tablets; or the metformin hydrochloride and mecobalamin composition granules are prepared by adopting wet granulation, hot-melt extrusion granulation or one-step granulation, and after the metformin hydrochloride and mecobalamin composition granules are prepared into blunt-release ordinary tablets, the release rate of the metformin hydrochloride can be adjusted to different degrees, so that the burst release phenomenon in the metformin hydrochloride preparation is controlled and reduced.
Compared with the prior art, the invention has the following beneficial effects:
(1) the pharmaceutical composition provided by the invention adopts the combination of metformin hydrochloride and mecobalamin, so that the reduction of vitamin B12 in a patient body caused by the use of metformin hydrochloride is reduced to a great extent, and thus, the diabetic peripheral neuropathy can be prevented and treated while the diabetes is treated, the defects that the existing medicines need to be taken respectively are overcome, and the curative effect is exact.
(2) In the pharmaceutical composition, the metformin hydrochloride in the sustained release tablets and the double-layer double-release tablets can be prepared by wet granulation, hot-melt extrusion granulation or one-step granulation, and can be used for smoothly releasing the metformin hydrochloride within 12 hours and reducing the stimulation of the metformin hydrochloride to the gastrointestinal tract.
(3) The metformin hydrochloride and mecobalamin pharmaceutical composition slow-release ordinary tablet is an administration design with high cost-effective ratio, can be prepared by wet granulation, hot-melt extrusion granulation or one-step granulation, delays the release for 15-60 minutes compared with the commercially available metformin hydrochloride ordinary tablet, can effectively slow down gastrointestinal adverse reactions of the metformin hydrochloride ordinary tablet, does not need to add a slow-release skeleton material with high proportion, and reduces the treatment cost and adverse reactions of patients.
Detailed Description
The present invention will be described in further detail with reference to the following examples. It should not be understood that the scope of the above-described subject matter of the present invention is limited to the following examples.
Example 1A pharmaceutical composition of metformin hydrochloride and mecobalamin
TABLE 1 formulation of metformin hydrochloride and mecobalamin pharmaceutical composition
The preparation method of the pharmaceutical composition of metformin hydrochloride and mecobalamin comprises the following steps:
s1) preparing metformin hydrochloride sustained-release granules: preparing metformin hydrochloride granules from metformin hydrochloride and an adhesive by wet granulation;
specifically, metformin hydrochloride and a binding agent in a formula amount are mixed, purified water is added for wet granulation, metformin hydrochloride wet granules are prepared, and the metformin hydrochloride wet granules are dried, granulated, mixed with a slow-release framework material and a lubricant, so as to obtain the metformin hydrochloride slow-release granules;
s2) preparing mecobalamin mixed powder: sieving and mixing mecobalamin, adhesive, filler, glidant and lubricant;
s3) pressing the metformin hydrochloride sustained-release granules obtained in the step S1 and the mecobalamin mixed powder obtained in the step S2 on a double-layer tablet press to obtain double-layer double-release tablets;
s4) coating the bilayer dual release tablet or the sustained release tablet of step S3 with a light-shielding coating agent; preparing a shading coating agent: the light-shading coating agent containing the dark iron oxide colored spindle is dissolved by pure water to prepare a 20% (w/w) solution, namely the light-shading coating agent.
Example 2A pharmaceutical composition of metformin hydrochloride and mecobalamin
TABLE 2 formulation of metformin hydrochloride with mecobalamin pharmaceutical composition
The preparation method of the pharmaceutical composition of metformin hydrochloride and mecobalamin comprises the following steps:
s1) preparing metformin hydrochloride sustained-release granules: preparing metformin hydrochloride sustained-release granules by carrying out hot-melt extrusion granulation on metformin hydrochloride, an adhesive, a sustained-release framework material and a lubricant;
specifically, metformin hydrochloride and a binder in a formula amount are mixed to obtain a physical mixture; setting the extrusion temperature of a double-screw extruder to be 150 ℃, starting the screw after the temperature rises to the set temperature, setting the rotating speed of the screw to be 80 revolutions per minute, adding the physical mixture into the double-screw extruder, extruding in a strip shape, cooling, crushing, sieving, and mixing with the slow-release framework material and the lubricant to obtain the metformin hydrochloride slow-release particles;
s2) preparing mecobalamin mixed powder: sieving and mixing mecobalamin, adhesive, filler, glidant and lubricant;
s3) pressing the metformin hydrochloride sustained-release granules obtained in the step S1 and the mecobalamin mixed powder obtained in the step S2 on a double-layer tablet press to obtain double-layer double-release tablets;
s4) coating the double-layered double release tablet of step S3 with a light-shielding coating agent; preparing a shading coating agent: the light-shading coating agent containing the dark iron oxide colored spindle is dissolved by pure water to prepare a 20% (w/w) solution, namely the light-shading coating agent.
Example 3A pharmaceutical composition of metformin hydrochloride and mecobalamin
TABLE 3 formulation of pharmaceutical composition of metformin hydrochloride and mecobalamin
The preparation method of the pharmaceutical composition of metformin hydrochloride and mecobalamin comprises the following steps:
s1) preparing metformin hydrochloride sustained-release granules: preparing metformin hydrochloride granules by adopting one-step granulation of a fluidized bed from metformin hydrochloride, an adhesive, a slow-release framework material and a lubricant;
specifically, dissolving the adhesive in water, and stirring until the solution is clear to obtain an adhesive aqueous solution; putting metformin hydrochloride with a formula amount into a fluidized bed granulator, setting the air inlet temperature to be 50-60 ℃, spraying an aqueous solution of an adhesive when the material temperature reaches 40 +/-5 ℃, performing fluidized bed granulation, drying, granulating, and mixing with a slow-release framework material and a lubricant to obtain metformin hydrochloride slow-release granules;
s2) preparing mecobalamin mixed powder: sieving and mixing mecobalamin, adhesive, filler, glidant and lubricant;
s3) pressing the metformin hydrochloride sustained-release granules obtained in the step S1 and the mecobalamin mixed powder obtained in the step S2 on a double-layer tablet press to obtain double-layer double-release tablets;
s4) coating the double-layered double release tablet of step S3 with a light-shielding coating agent; preparing a shading coating agent: the light-shading coating agent containing the dark iron oxide colored spindle is dissolved by pure water to prepare a 20% (w/w) solution, namely the light-shading coating agent.
Example 4A pharmaceutical composition of metformin hydrochloride and mecobalamin
TABLE 4 formulation of pharmaceutical composition of metformin hydrochloride and mecobalamin
The preparation method of the pharmaceutical composition of metformin hydrochloride and mecobalamin comprises the following steps:
s1) preparing granules by adopting hot-melt extrusion granulation;
mixing metformin hydrochloride and a binding agent according to the formula amount to obtain a physical mixture; setting the extrusion temperature of a double-screw extruder to be 150 ℃, starting a screw after the temperature rises to the set temperature, setting the rotating speed of the screw to be 80 revolutions/min, adding the physical mixture into the double-screw extruder, extruding in a strip shape, cooling, crushing, sieving by a 60-mesh sieve to obtain metformin hydrochloride particles, and mixing with mecobalamin, a slow-release framework material, a lubricant and a glidant to obtain metformin hydrochloride slow-release particles;
s2) tabletting the metformin hydrochloride sustained-release granules obtained in the step S1 on a tabletting machine to obtain tablet cores;
s3) coating the sustained-release tablet of step S2 with a light-shielding coating agent, wherein the light-shielding coating agent is formulated: the light-shading coating agent containing the dark iron oxide colored spindle is dissolved by pure water to prepare a 20% (w/w) solution, namely the light-shading coating agent.
Example 5A pharmaceutical composition of metformin hydrochloride and mecobalamin
TABLE 5 formulation of metformin hydrochloride with mecobalamin pharmaceutical composition
The preparation method of the pharmaceutical composition of metformin hydrochloride and mecobalamin comprises the following steps:
s1) preparing metformin hydrochloride, mecobalamin composition granules: preparing metformin hydrochloride granules by wet granulation of metformin hydrochloride, mecobalamin, a binding agent, a slow-release regulator and a lubricant;
specifically, the metformin hydrochloride, a binding agent and a slow-release regulator in the formula amount are mixed, and added with a mecobalamin aqueous solution for wet granulation to prepare metformin hydrochloride wet granules, and the metformin hydrochloride wet granules are dried, granulated, mixed with a lubricant to obtain metformin hydrochloride and mecobalamin composition granules;
s2) uniformly mixing the metformin hydrochloride, the mecobalamin composition granules and the lubricant in the step S1, and tabletting on a tabletting machine to obtain dull-release common tablets;
s3) coating the sustained release ordinary tablets of step S3 with a sunscreen coating agent; preparing a shading coating agent: the light-shading coating agent containing the dark iron oxide colored spindle is dissolved by pure water to prepare a 20% (w/w) solution, namely the light-shading coating agent.
Test one, Release Rate comparison test
1.1 test subjects: examples 1 to 4;
1.2 test methods: the pharmaceutical compositions of examples 1 to 4, which were equal in mass, were each placed in a phosphate buffer medium at a pH of 6.8 for detection.
1.3 test results:
table 6 release contrast results (pH6.8 dissolution medium) (n ═ 12)
As can be seen from Table 6, in the phosphate buffer medium with the pH value of 6.8, the metformin hydrochloride in the pharmaceutical composition of the embodiment has mild in-vitro release performance and no burst effect, the cumulative release degree in 10 hours is more than 85%, and although the pharmaceutical composition is used in the embodiments 1 to 4, the sustained release property of the single metformin hydrochloride sustained release tablet sold in the market within 12 hours is kept, and the effect of relieving gastrointestinal adverse reactions is maintained.
Experiment two, dissolution rate contrast experiment
2.1 test subjects: example 5 and a commercial metformin hydrochloride tablet, 0.5g each;
2.2 test methods: the pharmaceutical composition of example 5 was placed in a phosphate buffer medium at pH6.8 for testing.
2.3 test results
Table 7 dissolution rate comparison results (ph6.8 dissolution medium) (n ═ 12)
As can be seen from table 7: example 5 in hydrochloric acid medium with pH6.8, the dissolution rate is about 30 minutes slower than that of the commercial metformin hydrochloride tablet, the cumulative dissolution at 60min is 85.7 percent, which is equivalent to 86.5 percent of the cumulative dissolution at 30min of the commercial metformin hydrochloride tablet, and the slow dissolution can obviously slow down the gastrointestinal adverse reaction of the common metformin hydrochloride tablet.
The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.
Claims (4)
1. The pharmaceutical composition of metformin hydrochloride and mecobalamin is characterized in that the pharmaceutical composition is a blunt-release ordinary tablet;
the blunt-release common tablet comprises the following components in parts by weight: 250-1000 parts of metformin hydrochloride, 0.05-1.1 parts of mecobalamin, 30-300 parts of adhesive, 2-200 parts of blunt release regulator and 1-10 parts of lubricant.
2. The pharmaceutical composition of metformin hydrochloride and mecobalamin according to claim 1, wherein the binder comprises one or more of ethylene-vinyl acetate copolymer, polylactic-co-glycolic acid, copovidone, povidone, polyoxyethylene, polyvinyl alcohol, sodium carboxymethylcellulose, hydroxypropylcellulose, ethylcellulose and hydroxyethylcellulose.
3. The pharmaceutical composition of metformin hydrochloride and mecobalamin according to claim 1, wherein the slow-release modifier comprises one or more of methacrylic acid-ethyl acrylate copolymer, ethyl acrylate-methyl methacrylate copolymer, quaternary ammonium methacrylate copolymer, ethyl cellulose, stearyl alcohol, magnesium stearate, glyceryl behenate.
4. The process for preparing the metformin hydrochloride and mecobalamin pharmaceutical composition tablet for slow release according to claim 1, comprising the steps of:
s1) preparing metformin hydrochloride, mecobalamin composition granules: carrying out wet granulation, hot-melt extrusion granulation or fluidized bed one-step granulation on metformin hydrochloride, mecobalamin, an adhesive and a slow-release regulator to obtain metformin hydrochloride and mecobalamin composition granules;
s2) uniformly mixing the metformin hydrochloride and mecobalamin composition granules obtained in the step S1 and the lubricant, and tabletting on a tabletting machine to obtain a tablet core of an ordinary tablet with blunt release;
s3) coating the tablet core of the blunt-release conventional tablet of step S2 with a light-shielding coating agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011394210.5A CN112336739B (en) | 2020-05-27 | 2020-05-27 | Pharmaceutical composition of metformin hydrochloride and mecobalamin and preparation method thereof |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011394210.5A CN112336739B (en) | 2020-05-27 | 2020-05-27 | Pharmaceutical composition of metformin hydrochloride and mecobalamin and preparation method thereof |
| CN202010463154.XA CN111544409B (en) | 2020-05-27 | 2020-05-27 | Pharmaceutical composition of metformin hydrochloride and mecobalamin and preparation method thereof |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010463154.XA Division CN111544409B (en) | 2020-05-27 | 2020-05-27 | Pharmaceutical composition of metformin hydrochloride and mecobalamin and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112336739A true CN112336739A (en) | 2021-02-09 |
| CN112336739B CN112336739B (en) | 2022-03-22 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101428007A (en) * | 2008-12-04 | 2009-05-13 | 上海天赐福生物工程有限公司 | Process for producing diabecron sustained release tablet |
| CN103816130A (en) * | 2014-01-22 | 2014-05-28 | 悦康药业集团有限公司 | Metformin hydrochloride sustained-release tablet |
| CN107184559A (en) * | 2017-06-02 | 2017-09-22 | 广东赛康制药厂有限公司 | A kind of diabecron sustained-release tablet and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101579325B (en) * | 2009-06-16 | 2011-05-25 | 重庆康刻尔制药有限公司 | Metformin hydrochloride controlled-release tablet and preparation method thereof |
| EP2588139A1 (en) * | 2010-05-28 | 2013-05-08 | Bethesda Diabetes Research Centrum B.V. | New combination treatment for type 2 diabetes and other disorders related to insulin resistance |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101428007A (en) * | 2008-12-04 | 2009-05-13 | 上海天赐福生物工程有限公司 | Process for producing diabecron sustained release tablet |
| CN103816130A (en) * | 2014-01-22 | 2014-05-28 | 悦康药业集团有限公司 | Metformin hydrochloride sustained-release tablet |
| CN107184559A (en) * | 2017-06-02 | 2017-09-22 | 广东赛康制药厂有限公司 | A kind of diabecron sustained-release tablet and preparation method thereof |
Non-Patent Citations (1)
| Title |
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| 罗玮 等: "《甲钴胺对糖尿病口服二甲双胍患者的临床意义》", 《中国糖尿病杂志》 * |
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| Publication number | Publication date |
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| CN111544409B (en) | 2021-02-19 |
| CN111544409A (en) | 2020-08-18 |
| CN112336739B (en) | 2022-03-22 |
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