CN101683340A - Sustained-release preparation of compound metformin hydrochloride rosiglitazone and preparation method thereof - Google Patents
Sustained-release preparation of compound metformin hydrochloride rosiglitazone and preparation method thereof Download PDFInfo
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- CN101683340A CN101683340A CN200810222573A CN200810222573A CN101683340A CN 101683340 A CN101683340 A CN 101683340A CN 200810222573 A CN200810222573 A CN 200810222573A CN 200810222573 A CN200810222573 A CN 200810222573A CN 101683340 A CN101683340 A CN 101683340A
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Abstract
The invention relates to a sustained-release preparation of compound metformin hydrochloride rosiglitazone and a preparation method thereof; wherein, rosiglitazone and metformin hydrochloride have slow releasing characteristic in an in-vitro dissolution test, the rosiglitazone is released by 10-30 percent for a first hour, and is released by 60-80 percent for a fourth hour, and is released by morethan 80 percent for an eighth hour; the metformin hydrochloride is released by 15-40 percent for a first hour, is released by 50-70 percent for a fourth hour, and is released by more than 75 percentfor an eighth hour. The formula is mild and has prolonged action of glucose reduction, so as to avoid adverse reaction such as hypoglycemia and gastrointestine malaise, reduce taking times (one or twotimes each day), and improve compliance of a patient. The invention discloses the in-vitro drug-releasing characteristic of the sustained-release preparation and the preparation method thereof.
Description
Technical field
The present invention relates to slow releasing preparation of a kind of compound metformin hydrochloride rosiglitazone and preparation method thereof.
Background technology
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.
Rosiglitazone system is by increasing tissue to insulin sensitivity, improves cell is brought into play blood sugar lowering to the utilization of glucose curative effect, can obviously reduce fasting glucose and insulin and C-peptide level, and post-prandial glycemia and insulin are also had tangible reduction effect.Glycolated hemoglobin (HbAlc) level is obviously reduced.Its mechanism of action activates a kind of nuclear receptor with specificity: (PPAR γ) is relevant for the activated γ-receptor of peroxisome proliferator.The mankind, crucial target tissue that PPAR γ receptor is distributed in some insulin actions is as fatty tissue, skeletal muscle and liver etc.The effect of PPAR γ nuclear receptor is to regulate the insulin response genetic transcription, and the insulin response gene participates in the generation of control glucose, transhipment and utilizes.In addition, PPAR gamma reaction gene is also regulated fatty acid metabolism.
More than the mechanism of action difference of two kinds of hypoglycemic medicines, but the The combined application can be played complementary hypotensive effect.At present, this compound preparation listing 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.
Summary of the invention
The invention provides a kind of is compound slow release preparation of active component and preparation method thereof with metformin hydrochloride and rosiglitazone.Wherein rosiglitazone is the active component meter, can exist with forms such as maleate, succinate, benzene sulfonate, hydrochlorates.
Slow releasing preparation described in the invention, the amount that described each preparation unit contains the active component rosiglitazone is 4-8mg, the amount that contains the active ingredient hydrochloric acid metformin is 125-750mg, is preferably 250-500mg.Both preferred compound recipe unitized doses are rosiglitazone 4mg+ metformin hydrochloride 250mg; Rosiglitazone 8mg+ metformin hydrochloride 500mg.
In this compositions, low unitized dose can exist with the form of slow releasing tablet, slow-releasing granules, sustained-release micro-pill capsules, and the high dose combination then mainly exists with slow releasing tablet and the particulate form of slow release.Two kinds of active component all present slow release characteristics, wherein:
Lattice row ketone slow-released part is characterized in that in the dissolution in vitro test: discharged 10-30%, discharged 60-80%, discharged more than 80% on the 8th hour in the 4th hour in the 1st hour
The diabecron sustained-release part is in the dissolution in vitro test: discharged 15-40%, discharged 50-70%, discharged more than 75% on the 8th hour in the 4th hour in the 1st hour.
Metformin hydrochloride and rosiglitazone 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, RS 30D, 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.
Compound slow release preparation described in the invention is used for the treatment of the dependence diet control and tempers the effectively type ii diabetes of blood sugar control.This compound preparation can be gentle and long-acting blood sugar lowering, both can avoid untoward reaction such as hypoglycemia, gastrointestinal upset, can reduce again and take number of times, only need take once (high dose combination of the present invention) or secondary (low dosage combination of the present invention) every day and get final product, can obviously improve patient's compliance and compliance.
The specific embodiment
Come compound metformin hydrochloride rosiglitazone slow releasing preparation of the present invention and preparation method thereof done further specifying by following example, but be not limited in following example.
Embodiment 1: the metformin hydrochloride and rosiglitazone double-layer sustained release tablets
Prescription:
Preparation method:
Metformin hydrochloride is crossed 100 mesh sieves, and HPMC-15M, HPMC-4M, microcrystalline Cellulose are crossed 60 mesh sieves, and with 80% alcoholic solution system soft material, 20 mesh sieves are granulated behind the supplementary material mix homogeneously, 40 ℃ of dryings, and 18 mesh sieve granulate, standby; In addition with rosiglitazone and lactose, calcium hydrogen phosphate, acrylic resin RS100, the mixing three times of sieving is with the method granulate.Take by weighing above two kinds of granules respectively in proportion, be pressed into double-layer sustained release tablets after the adding magnesium stearate.
Embodiment 2 compound metformin hydrochloride rosiglitazone film-coat slow releasing tablet
Prescription:
Preparation method:
Metformin hydrochloride, rosiglitazone are crossed 100 mesh sieves, standby; Get metformin hydrochloride, with microcrystalline Cellulose 300g mix homogeneously, with 3% 30 POVIDONE K 30 BP/USP-30 aqueous solution system soft material, 20 mesh sieves are granulated, drying, and 18 mesh sieve granulate, standby; Other gets rosiglitazone, and with surplus microcrystalline Cellulose, calcium hydrogen phosphate, the abundant mix homogeneously of silicon dioxide, the same method is prepared into granule, and is standby; Two kinds of granules are mixed the back add magnesium stearate, it is even always to be mixed, tabletting; In the configuration 8%EC aqueous dispersion aqueous solution, stir, standby; 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 (about 8-16% increases weight), and 40 ℃ of heat preservation hot are incubated the about 2h of film-coat, and discharging gets final product.
Embodiment 3 compound metformin hydrochloride rosiglitazone sustained-release micro-pill capsules
Prescription:
Preparation method:
Metformin hydrochloride, rosiglitazone, HPMC-K4M, HPMC-K10M are crossed 60 mesh sieves, add the wet soft material of 60% 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, after the fluidized drying, fill in the capsule shells, promptly.
Embodiment 4 compound metformin hydrochloride rosiglitazone sustained release coating pellet capsules
Prescription:
Preparation method:
Metformin hydrochloride, rosiglitazone are crossed 100 mesh sieves, standby; Get metformin hydrochloride, rosiglitazone, with HPMC-K100M, microcrystalline Cellulose, ethyl cellulose (adjuvant is crossed 60 mesh sieves), behind the supplementary material mix homogeneously, add the wet soft material of 50% 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, drying filled in the capsule and gets final product.
Embodiment 5 compound metformin hydrochloride rosiglitazone slow-releasing granules
Prescription:
Preparation method:
Metformin hydrochloride, rosiglitazone are crossed 100 mesh sieves, add lactose, microcrystalline Cellulose mix homogeneously, Brazil wax, glyceryl monostearate are added fusion, getting the above-mentioned metformin hydrochloride supplementary material that mixes joins wherein, continue to stir and to allow its slow cooling, scrape concretion, cross 16 mesh sieves and granulate, promptly.
The external dissolution test of embodiment 6 compound slow release preparations of the present invention
The preparation of the present invention such as embodiment 4 preparations 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: 60rpm
Dissolution medium: hydrochloric acid solution (simulated gastric fluid) changes phosphate buffer (simulated intestinal fluid) over to after 1 hour, 2 hours
Stripping volume: 1000ml
Measurement result is as follows:
Table one: metformin hydrochloride dissolution determination result
The result shows: the external result of extraction effect of metformin hydrochloride, rosiglitazone and conforming to that the present inventor designs in the preparation.
Claims (8)
1. the slow releasing preparation of compound metformin hydrochloride and rosiglitazone is characterized in that two kinds of effective ingredient all present slow release characteristics.Described rosiglitazone is the active component meter, can exist with forms such as maleate, succinate, benzene sulfonate, hydrochlorates.
2. the slow releasing preparation of claim 1 is characterized in that, the amount that described each preparation unit contains the active component rosiglitazone is 4-8mg, and the amount that contains the active ingredient hydrochloric acid metformin is 125-750mg, is preferably 250-500mg.Both preferred compound recipe unitized doses are rosiglitazone 4mg+ metformin hydrochloride 250mg; Rosiglitazone 8mg+ metformin hydrochloride 500mg.
Low unitized dose can exist with the form of slow releasing tablet, slow-releasing granules, sustained-release micro-pill capsules, and the high dose combination then mainly exists with slow releasing tablet and the particulate form of slow release.
3. the slow releasing preparation of claim 1, described rosiglitazone slow-release part is characterized in that, in the dissolution in vitro test: discharged 10-30%, discharged 60-80%, discharged more than 80% on the 8th hour in the 4th hour in the 1st hour.
4. the slow releasing preparation of claim 1, described diabecron sustained-release part is characterized in that in the dissolution in vitro test: discharged 15-40%, discharged 50-70%, discharged more than 75% on the 8th hour in the 4th hour in the 1st hour.
5. the described arbitrary slow releasing preparation of claim 1-4 is characterized in that, comprises 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.
6. the described slow releasing preparation of claim 5, it is characterized in that, sustained-release matrix comprises 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.
7. the described slow releasing preparation of claim 5, it is characterized in that coated formula 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.
8. the described compound slow release preparation of claim 1 can be used for treating the dependence diet control and tempers the effectively type ii diabetes of blood sugar control.
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| Application Number | Priority Date | Filing Date | Title |
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| CN200810222573A CN101683340A (en) | 2008-09-22 | 2008-09-22 | Sustained-release preparation of compound metformin hydrochloride rosiglitazone and preparation method thereof |
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| CN200810222573A CN101683340A (en) | 2008-09-22 | 2008-09-22 | Sustained-release preparation of compound metformin hydrochloride rosiglitazone and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102423313A (en) * | 2011-12-26 | 2012-04-25 | 盛世泰科生物医药技术(苏州)有限公司 | Compound controlled-release preparation of rosiglitazone and metformin hydrochloride |
| CN107080846A (en) * | 2010-07-09 | 2017-08-22 | 詹姆斯.特林卡.格林 | For the combination including short-half-life medicine net Rui Gelie immediately/sustained release delivery system |
| CN115227660A (en) * | 2022-09-21 | 2022-10-25 | 北京惠之衡生物科技有限公司 | Metformin hydrochloride sustained release tablet and preparation method thereof |
-
2008
- 2008-09-22 CN CN200810222573A patent/CN101683340A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107080846A (en) * | 2010-07-09 | 2017-08-22 | 詹姆斯.特林卡.格林 | For the combination including short-half-life medicine net Rui Gelie immediately/sustained release delivery system |
| CN102423313A (en) * | 2011-12-26 | 2012-04-25 | 盛世泰科生物医药技术(苏州)有限公司 | Compound controlled-release preparation of rosiglitazone and metformin hydrochloride |
| CN115227660A (en) * | 2022-09-21 | 2022-10-25 | 北京惠之衡生物科技有限公司 | Metformin hydrochloride sustained release tablet and preparation method thereof |
| CN115227660B (en) * | 2022-09-21 | 2022-12-16 | 北京惠之衡生物科技有限公司 | Metformin hydrochloride sustained release tablet and preparation method thereof |
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Open date: 20100331 |