CN1391890A - Oral melbine hydrocloride slow-releasing prepn and its preparing method - Google Patents
Oral melbine hydrocloride slow-releasing prepn and its preparing method Download PDFInfo
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- CN1391890A CN1391890A CN 02133574 CN02133574A CN1391890A CN 1391890 A CN1391890 A CN 1391890A CN 02133574 CN02133574 CN 02133574 CN 02133574 A CN02133574 A CN 02133574A CN 1391890 A CN1391890 A CN 1391890A
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Abstract
The present invention provides a type-II diabetes treating medicine, which can be released inside body for stable medicine concentration in body, prolonged half life, raised effect and lower toxicity. By means of unique delayed release technology, high-viscosity polymer is utilized to form gel via water absorbing expansion and delay released table is made for taking once each day. The present invention is used in dietotherapy of type-II diabetes and in controlling blood sugar for those with less exercise.
Description
The present invention relates to the prescription and the preparation method of medicine.Especially for melbine hydrocloride slow-releasing preparation for the treatment of type ii diabetes and preparation method thereof.
Now, diabetes have become " No. three killer " who threatens the mankind after tumor and cardiovascular and cerebrovascular disease in the world.No matter in developed country or developing country, the sickness rate of diabetes is all in rapid rising.According to the data that World Health Organization (WHO) announces, there were 3,000 ten thousand diabetes patients in the whole world in 1985, had increased to 1.35 hundred million by 1997.According to internal authority diabetes epidemiology scholarly forecast, by 2010, global diabetes patient will reach 2.4 hundred million, and the year two thousand fifty then can be increased to 300,000,000 people.Diabetes have become the great public health problem that countries in the world are paid close attention to as a kind of serious non-infectious chronic disease.The situation of China is no exception.Have data to show, China adult's in 1979 onset diabetes rate less than 1% has risen to 2.65% by 1997, and the annual in recent years speed with 0.1% increases sharply.Show from extensive epidemiological investigation result 11 provinces in the whole nation, city people more than 40,000, among present 20～74 years old crowd of China, the sickness rate of diabetes is 2.2%, the sickness rate of impaired glucose tolerance (being prediabetes) is more up to 3.8%, the diabetics that this means present 20～74 years old age bracket crowd of China surpasses 2,000 ten thousand, and " reserves " then reaches 3,000 ten thousand people.And 90% is type 2 diabetes mellitus, and for this reason, for the insider, researching and developing safely and effectively, antidiabetic medicine has become the task of top priority.(see 1, market research of south medication economics institute information centre of National Drug Administration, " national oral diabetes medication market survey report "; 2, diabetes 123 medical information nets, on February 6th, 2000: " oral antidiabetic drug, who control the situation ").
Metformin hydrochloride is a kind of biguanides antidiabetic drug of can be oral and being used widely, it is the unique oral biguanides hyperglycemia medicine that present world developed country is still using, can improve the tolerance of type-II diabetes patient to sugar, reduce the basis and reach plasma glucose concentration after the meal, mechanism of action is different with other antidiabetic medicines.Metformin hydrochloride reduces glycogen and generates, and small intestinal is reduced the absorption of sugar, by increasing the opposing that periphery is improved insulin to the picked-up and the utilization of sugar.In normal person and type-II diabetes patient, do not produce hypoglycemic reaction, do not produce hyperinsulinemia yet.The metformin hydrochloride that uses clinically at present is conventional tablet and capsule etc., and common dose is grams every days 1.5, divides and takes for 3 times.Therefore, must medicine time is spaced apart regularly, could guarantee that blood drug level keeps treatment level.Exist patient to take inconvenience, easily forget clothes, miss, shortcoming such as blood concentration fluctuation is big.
The present invention provides a kind of in order to overcome above-mentioned weak point of the prior art just and can slowly discharge in vivo, it is steady to keep blood drug level, half-life prolongs, the hypoglycemic medicine that is used for the treatment of type ii diabetes of safety, efficient, low toxicity, taking convenience: diabecron sustained-release tablet and preparation method thereof.
The special character of pharmaceutical composition prescription of the present invention is: its pharmaceutical composition prescription is 250～500g by per 1000 re-computation, 1. hydrochloric metformin and weight; 2. contain medicinal excipient water-soluble high-molecular substance in the slow release prescription: diluent and weight are that 5～400g, binding agent and weight are 5～400g; Excipient water-insoluble polymer substance: binding agent and weight are 5～100g; Organic carboxyl acid or alcohol and weight are that 5～200g, lubricant and weight are 6.6～36.6g; 3. can make the slow releasing tablet taken in 1st once, also can be made into the slow release Film coated tablets; 4. the rate of release of said preparation is by being the erosion type control drug release that make on the basis with water soluble polymer or water-insoluble macromolecule, the release of its rate of release 1～3hr is 10～60% of a labelled amount, the release of 2～8hr is 30～80% of a labelled amount, and the release of＞6hr is 70% of a labelled amount; 5. the ratio of metformin hydrochloride and fatty acid/alcohol can preferably be selected between 100: 2～100: 60 a variation in 100: 1 to 100: 100.
Above-mentioned pharmaceutical excipient is that 1. water-soluble high-molecular substances are hypromellose, polyvinylpyrrolidone, sodium carboxymethyl cellulose, carboxymethyl starch sodium or their mixture; The water-insoluble polymer substance is: acrylic resin, dextrin or microcrystalline Cellulose, starch, organic acid carboxylic acid or aliphatic alcohol, Pulvis Talci, micropowder silica gel, magnesium stearate or their mixture; 2. diluent is starch, carboxymethyl starch sodium, dextrin or microcrystalline Cellulose; 3. binding agent is starch, hypromellose, acrylic resin, polyvinylpyrrolidone, sodium carboxymethyl cellulose or their mixture; 4. fluidizer or lubricant are Pulvis Talci, micropowder silica gel, organic acid carboxylic acid or aliphatic alcohol and magnesium stearate or their mixture.
The preparation method of oral melbine hydrocloride slow-releasing preparation of the present invention is: raw material and excipient are crossed 80-100 mesh sieve, mixing, organic carboxyl acid or alcohol are heated to the melting state in 50～60 ℃ of water-baths, after adding the rapidly abundant mixing of metformin hydrochloride, add the binding agent mixing again and make dried wet moderate soft material, cross 16～30 mesh sieve granulate, add auxiliary agent or the abundant mixing of lubricant before the tabletting, granule content after the assay was approved, compress tablet coating is promptly.
The present invention compared with prior art has following advantage: adopt unique slow release method, utilize the imbibition of high viscosity macromolecular material to form gel, make the slow releasing tablet that only need take every day once, can delay the medicine holdup time in vivo, medicine is slowly discharged in vivo, blood drug level is steady, half-life prolongs, it is long to keep the effective blood drug concentration time, have more long-lasting, thereby reduced the number of times of medication.Blood drug level is more steady, and it is little to fluctuate.Both make things convenient for patient to take, can reduce toxic and side effects again.Metformin has recorded in 2000 editions Chinese Pharmacopoeias, China's approved dosage form productions such as raw material, conventional tablet, capsule, slow releasing preparation is at present domestic manufacturer production as yet, this product succeed in developing the hypoglycemic drug that a safety, efficient, low toxicity, taking convenience can be provided to the patient.
The present invention is described in further detail below with reference to embodiment:
1. 1 kinds of oral melbine hydrocloride slow releasing tablet of embodiment, its prescription is per 1000 and contains following material: crude drug: metformin hydrochloride 500g, excipient has: binding agent: hypromellose 250g, diluent: microcrystalline Cellulose 10g, binding agent: 20% acrylic resin II 40g, fluidizer or lubricant: magnesium stearate 36.6g.
The preparation method of above-mentioned oral melbine hydrocloride slow-releasing preparation, be that metformin hydrochloride and hypromellose and microcrystalline Cellulose are crossed 80 mesh sieves, mixing, then add to make for 20% acrylic resin II number and do wet moderate soft material, cross 16 mesh sieve granulate, add the abundant mixing of magnesium stearate before the tabletting, granule content after the assay was approved, the compress tablet coating Opadry adds 40% ethanol, 2% suspension, coating promptly.
2. 1 kinds of oral melbine hydrocloride slow releasing tablet of embodiment, its prescription is per 1000 and contains following material: crude drug: metformin hydrochloride 250g, excipient has: binding agent: hypromellose 400g, sodium carboxymethyl cellulose 5g, microcrystalline Cellulose 5g, carboxymethyl starch sodium 100g, binding agent: 20% acrylic resin II 40g, fluidizer or lubricant: magnesium stearate 36.6g.
The preparation method of above-mentioned oral melbine hydrocloride slow-releasing preparation: with metformin hydrochloride and hypromellose, sodium carboxymethyl cellulose, microcrystalline Cellulose, carboxymethyl starch sodium, cross 100 mesh sieves, mixing, add 20% acrylic resin II number and become to do wet moderate soft material, cross 30 mesh sieve granulate, add the abundant mixing of magnesium stearate before the tabletting, granule content after the assay was approved, tabletting is promptly.
3. 1 kinds of oral melbine hydrocloride slow releasing tablet of embodiment, its prescription is per 1000 and contains following material: crude drug: metformin hydrochloride 500g, excipient has: binding agent: hypromellose 200g, diluent: carboxymethyl starch sodium 40g, binding agent: ethyl cellulose 50g, 20% ethyl cellulose 40g, fluidizer or lubricant: magnesium stearate 6.6g.
The preparation method of above-mentioned oral melbine hydrocloride slow-releasing preparation, be that metformin hydrochloride and hypromellose, Sodium Hydroxymethyl Stalcs, ethyl cellulose and 20% ethyl cellulose are crossed 80 mesh sieves, mixing, make and do wet moderate soft material, cross 16 mesh sieve granulate, add the abundant mixing of magnesium stearate before the tabletting, granule content after the assay was approved, the compress tablet coating Opadry adds 60% ethanol, 8% suspension, coating promptly.
4. 1 kinds of oral melbine hydrocloride slow releasing tablet of embodiment, its prescription is per 1000 and contains following material: crude drug: metformin hydrochloride 500g, excipient has: fluidizer or lubricant: octadecanol 200g, stearic acid 5g, diluent: starch 80g, binding agent: 20% acrylic resin II 5g. fluidizer or lubricant: magnesium stearate 6.6g.
The preparation method of above-mentioned oral melbine hydrocloride slow-releasing preparation, be that metformin hydrochloride is crossed 100 mesh sieves, octadecanol and stearic acid are heated to the melting state in 60 ℃ of water-baths, after adding the rapidly abundant mixing of metformin hydrochloride, add the starch mixing again, then add to make for 20% acrylic resin II number and do wet moderate soft material, cross 24 mesh sieve granulate, add the abundant mixing of magnesium stearate before the tabletting, granule content after the assay was approved, the compress tablet coating Opadry adds 80% ethanol, 6% suspension, and coating promptly.
5. 1 kinds of oral melbine hydrocloride slow releasing tablet of embodiment, its prescription is to contain following material by per 1000: crude drug: metformin hydrochloride 500g, excipient has: fluidizer or lubricant: octadecanol 130g, diluent: microcrystalline Cellulose 150g, binding agent: acrylic resin II 10g, 20% polyvinylpyrrolidone 10g, fluidizer or lubricant: magnesium stearate 6.6.
The preparation method of above-mentioned oral melbine hydrocloride slow-releasing preparation, be that metformin hydrochloride is crossed 80 mesh sieves, octadecanol is heated to the melting state in 55 ℃ of water-baths, after adding the rapidly abundant mixing of metformin hydrochloride, add microcrystalline Cellulose and acrylic acid resin II mixing again, then add 20% polyvinylpyrrolidone and make dried wet moderate soft material, cross 24 mesh sieve granulate, add the abundant mixing of magnesium stearate before the tabletting, granule content after the assay was approved, tabletting is promptly.
6. 1 kinds of oral melbine hydrocloride slow releasing tablet of embodiment, its prescription is to contain following material by per 1000: crude drug: metformin hydrochloride 500g, excipient has: binding agent: hypromellose 5g, fluidizer or lubricant: stearic acid 200g, binding agent: acrylic resin II 100g, polyvinylpyrrolidone 5g, 20% acrylic resin IV 5g, fluidizer or lubricant: magnesium stearate 6.6g.
The preparation method of above-mentioned oral melbine hydrocloride slow-releasing preparation: be that metformin hydrochloride and hypromellose are crossed 80 mesh sieves, mixing, stearic acid is heated to the melting state in 50 ℃ of water-baths, after adding the rapidly abundant mixing of metformin hydrochloride, adding acrylic resin II number, polyvinylpyrrolidone, 20% acrylic resin IV again number makes and to do wet moderate soft material, cross 24 mesh sieve granulate, add the abundant mixing of magnesium stearate before the tabletting, granule content after the assay was approved, the compress tablet coating Opadry adds 60% ethanol, 4% suspension, and coating promptly.
7. 1 kinds of oral melbine hydrocloride slow releasing tablet of embodiment, its prescription is to contain following material by per 1000: crude drug: metformin hydrochloride 500g, excipient has: binding agent: hypromellose 180g, microcrystalline Cellulose 60g, sodium carboxymethyl cellulose 60g, carboxymethyl starch sodium 5g, 20% polyvinylpyrrolidone 100g, fluidizer or lubricant: magnesium stearate 6.6g
The preparation method of above-mentioned oral melbine hydrocloride slow-releasing preparation, be that metformin hydrochloride and hypromellose, microcrystalline Cellulose, sodium carboxymethyl cellulose and carboxymethyl starch sodium are crossed 80 mesh sieves, mixing, then add to make for 20% acrylic resin II number and do wet moderate soft material, cross 16 mesh sieve granulate, add the abundant mixing of magnesium stearate before the tabletting, granule content after the assay was approved, the compress tablet coating Opadry adds 40% ethanol, 2% suspension, coating promptly.
Crude drug in the foregoing description 1～7 and solid excipient are all crossed the 80-100 mesh sieve when getting the raw materials ready stand-by.
Claims (3)
1. oral melbine hydrocloride slow-releasing preparation, its pharmaceutical composition prescription is characterised in that by per 1000 re-computation:
1.1 hydrochloric metformin and weight are 250～500g;
1.2 contain medicinal excipient water-soluble high-molecular substance in the slow release prescription: diluent and weight are that 5～400g, binding agent and weight are 5～400g; Excipient water-insoluble polymer substance: binding agent and weight are 5～100g; Organic carboxyl acid or alcohol and weight are that 5～200g, lubricant and weight are 6.6～36.6g;
1.3 can make the slow releasing tablet taken in 1st once, also can be made into the slow release Film coated tablets;
1.4 the rate of release of said preparation is by being the erosion type control drug release that make on the basis with water soluble polymer or water-insoluble macromolecule, the release of its rate of release 1～3hr is 10～60% of a labelled amount, the release of 2～8hr is 30～80% of a labelled amount, and the release of＞6hr is 70% of a labelled amount;
1.5 the ratio of metformin hydrochloride and fatty acid/alcohol can preferably be selected between 100: 2～100: 60 a variation in 100: 1 to 100: 100.
2. according to the described oral melbine hydrocloride slow-releasing preparation of claim 1, it is characterized in that: said pharmaceutical excipient has:
2.1 water-soluble high-molecular substance is hypromellose, polyvinylpyrrolidone, sodium carboxymethyl cellulose, carboxymethyl starch sodium or their mixture; The water-insoluble polymer substance is: acrylic resin, dextrin or microcrystalline Cellulose, starch, organic acid carboxylic acid or aliphatic alcohol, Pulvis Talci, micropowder silica gel, magnesium stearate or their mixture;
2.2 diluent is starch, carboxymethyl starch sodium, dextrin or microcrystalline Cellulose or their mixture;
2.3 binding agent is starch, hypromellose, acrylic resin, polyvinylpyrrolidone, sodium carboxymethyl cellulose or their mixture;
2.4 fluidizer or lubricant are Pulvis Talci, micropowder silica gel, organic acid carboxylic acid or aliphatic alcohol and magnesium stearate or their mixture.
3. the method for preparing claim 1 oral melbine hydrocloride slow-releasing preparation, it is characterized in that: raw material and excipient are crossed 80～100 mesh sieves, mixing, organic carboxyl acid or alcohol are heated to the melting state in 50～60 ℃ of water-baths, after adding the rapidly abundant mixing of metformin hydrochloride, add the binding agent mixing again and make dried wet moderate soft material, cross 16～30 mesh sieve granulate, add auxiliary agent or the abundant mixing of lubricant before the tabletting, granule content after the assay was approved, compress tablet coating is promptly.
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| CN 02133574 CN1391890A (en) | 2002-08-05 | 2002-08-05 | Oral melbine hydrocloride slow-releasing prepn and its preparing method |
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| CN 02133574 CN1391890A (en) | 2002-08-05 | 2002-08-05 | Oral melbine hydrocloride slow-releasing prepn and its preparing method |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1330298C (en) * | 2005-05-26 | 2007-08-08 | 贵阳新天药业股份有限公司 | Oral liquid of metformin hydrochloride and preparation method |
| CN100455279C (en) * | 2004-04-29 | 2009-01-28 | 美时化学制药股份有限公司 | Oral administered sustained release lozenge composition and its preparation method |
| WO2010111905A1 (en) * | 2009-03-31 | 2010-10-07 | 江苏恒瑞医药股份有限公司 | Pharmaceutical composition for treatment of 2 type dabetes |
| CN106963740A (en) * | 2017-03-27 | 2017-07-21 | 华益药业科技(安徽)有限公司 | A kind of diabecron sustained-release tablet and preparation method thereof |
| CN107898767A (en) * | 2018-01-03 | 2018-04-13 | 临沂大学 | A kind of dog diabecron sustained-release chewable tablets and preparation method thereof |
| CN109758431A (en) * | 2017-11-09 | 2019-05-17 | 郑州泰丰制药有限公司 | A kind of metformin hydrochloride tablet and preparation method thereof |
| CN111110648A (en) * | 2020-01-13 | 2020-05-08 | 新发药业有限公司 | Metformin hydrochloride controlled release tablet |
-
2002
- 2002-08-05 CN CN 02133574 patent/CN1391890A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100455279C (en) * | 2004-04-29 | 2009-01-28 | 美时化学制药股份有限公司 | Oral administered sustained release lozenge composition and its preparation method |
| CN1330298C (en) * | 2005-05-26 | 2007-08-08 | 贵阳新天药业股份有限公司 | Oral liquid of metformin hydrochloride and preparation method |
| WO2010111905A1 (en) * | 2009-03-31 | 2010-10-07 | 江苏恒瑞医药股份有限公司 | Pharmaceutical composition for treatment of 2 type dabetes |
| US8476272B2 (en) | 2009-03-31 | 2013-07-02 | Jiangsu Hengrui Medicine Co., Ltd. | Pharmaceutical composition for treatment of type 2 diabetes |
| CN106963740A (en) * | 2017-03-27 | 2017-07-21 | 华益药业科技(安徽)有限公司 | A kind of diabecron sustained-release tablet and preparation method thereof |
| CN109758431A (en) * | 2017-11-09 | 2019-05-17 | 郑州泰丰制药有限公司 | A kind of metformin hydrochloride tablet and preparation method thereof |
| CN107898767A (en) * | 2018-01-03 | 2018-04-13 | 临沂大学 | A kind of dog diabecron sustained-release chewable tablets and preparation method thereof |
| CN107898767B (en) * | 2018-01-03 | 2021-07-20 | 临沂大学 | Metformin hydrochloride sustained-release chewable tablet for dogs and preparation method thereof |
| CN111110648A (en) * | 2020-01-13 | 2020-05-08 | 新发药业有限公司 | Metformin hydrochloride controlled release tablet |
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