CN103417496A - Method for preparing metformin hydrochloride controlled-release pellet preparation - Google Patents
Method for preparing metformin hydrochloride controlled-release pellet preparation Download PDFInfo
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- CN103417496A CN103417496A CN2013103750698A CN201310375069A CN103417496A CN 103417496 A CN103417496 A CN 103417496A CN 2013103750698 A CN2013103750698 A CN 2013103750698A CN 201310375069 A CN201310375069 A CN 201310375069A CN 103417496 A CN103417496 A CN 103417496A
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Abstract
The invention relates to a method for preparing a metformin hydrochloride controlled-release pellet preparation. A metformin hydrochloride controlled-release pellet is composed of a drug-contained pellet core and a controlled-release layer. The drug-contained pellet is composed of metformin hydrochloride, a filling agent and an adhesive. The controlled-release layer is composed of a controlled-release material and a pore-foaming agent. The metformin hydrochloride controlled-release pellet is mixed with pioglitazone hydrochloride controlled-release pellets to obtain the compounded metformin hydrochloride/pioglitazone hydrochloride controlled-release pellet preparation which achieves the ideal effect of regulating a blood sugar level, can reduce toxic and side effects of drugs, can achieve the effect of continuously and stably reducing the blood sugar level in the body, and facilitate improvement of the compliance of a patient. The compounded metformin hydrochloride controlled-release pellet preparation has high bioavailability and stable blood concentration. Clinical effects are effectively improved and a better dosage regimen and a better treatment effect are provided for domestic and overseas diabetics.
Description
Technical field
The present invention relates to diabetes pharmaceutical technology field, especially a kind of compound formulation of diabecron sustained-release pellet preparations.
Background technology
Diabetes (diabetes) are to act on that body causes hypoinsulinism, insulin resistant etc. and a series of metabolism disorder syndromes such as the sugar that causes, protein, fat, power and water Xie Zhi by inherited genetic factors, immunologic function disorder, infected by microbes and toxin thereof, free radical toxin, Nervous and Mental Factors etc. various virulence factors.Take hyperglycemia clinically as main feature, the performance such as polyuria, polydipsia, polyphagia can appear in model case, become thin, i.e. " three-many-one-little " symptom; Diabetes (blood glucose) cause complication once control bad meeting, cause the exhaustion pathological changes at the positions such as kidney, eye, foot, and can't cure; Diabetes have become commonly encountered diseases and the frequently-occurring disease in China and even the world, and have become one of disease that M & M is the highest.Diabetes are divided into amphitypy, and the I type is insulin dependent diabetes mellitus (IDDM), and the II type is non-insulin-dependent diabetes mellitus.Wherein II type non-insulin-dependent diabetes mellitus patient is in the majority, accounts for more than 90% of patient's sum.
Metformin hydrochloride is a kind of biguanides oral antidiabetic drug, for the treatment of non-insulin-dependent diabetes mellitus.This medicine Main Function is organized outside islets of langerhans, suppresses enterocyte and absorbs glucose, increases the sensitivity of surrounding tissue to insulin, increases non-insulin and relies on gluconeogenesis function of liver.The hypoglycemic activity of biguanides does not rely on normal islet function and B cell, but increases the anerobic glycolysis of glucose, suppresses the hepatic glycogen heteroplasia, reduces blood plasma glucagon level.Pioglitazone hydrochloride is the Studies of The Insulin Sensitizer Thiazolidinediones medicine, and it can increase insulin sensitivity, reduces blood glucose.The competitive peroxide activator enzyme paraphyte receptor of such medicine energy, regulate transcribing of Insulin sensitivity gene, increase transcribing with albumen of peripheral tissues's glucose transporter 1 and glucose transporter 4 etc. synthetic, increase picked-up and the transhipment of basic glucose, thereby change insulin resistant and performance hypoglycemic activity.Metformin hydrochloride and pioglitazone hydrochloride can improve insulin resistant from different approach.When pioglitazone hydrochloride and metformin hydrochloride coupling, pioglitazone has improved the sensitivity of tissue to insulin, and the anerobic glycolysis that makes metformin hydrochloride improve surrounding tissue is better brought into play with the effect that increases surrounding tissue insulin and its receptors bind.The time limit of the two hypoglycemic activity supplements mutually, and curative effect superposes mutually, and side effect offsets.It is the good combination that treatment onset type Ⅱdiabetes mellitus especially improves insulin resistant.
Pellet capsule belongs to polydisperse system, each dosage is usually containing tens or a hundreds of micropill, micropill is compared with the slow-release tablet of a unit drug-supplying system, there are the characteristics such as concise production process, drug loading are large, good fluidity, favorable reproducibility, good stability, be widely used in the medicine sustained and controlled release preparation.The sustained-release micro-pill capsules preparation is developed rapidly in recent years, and domestic had a more report about slow release capsule preparation, and the Related products such as slow releasing capsule, enteric coated capsule are being sold on the market.But the research to compound sustained release capsules is relatively less, the domestic listing of also not ratifying compound sustained release capsules at present; The domestic existing listing of the common compound tablet of metformin hydrochloride and pioglitazone hydrochloride, its compound slow-release tablet also obtained the U.S. FDA approval in 2009, but to the domestic report that there is no of the research of compound sustained-release pellet capsule.
The patent document that number of patent application is 20101051.527.0 discloses the compound preparation of a kind of pioglitazone hydrochloride and metformin hydrochloride double-layer osmotic pump controlled-release tablet composition, on forming, structure comprises successively from the inside to the outside: the label formed by medicated layer and boosting layer, the contagion gown layer, clothing film with drug release hole, pioglitazone hydrochloride release layer and nonessential aesthstic coat, this invention adopts the double-layer osmotic pump controlled-release technology, the later stage of improving metformin hydrochloride discharges, yet preparation technology and the equipment of existing double layer osmotic pump technology are not perfect, this invention exists the feasibility problem of suitability for industrialized production, and in double-layer osmotic pump tablet, propellant adds the content that has limited every active medicine, need day to take multi-disc and just can reach effective dose, undesirable aspect raising patient medication compliance.
In view of the foregoing, now invent out a kind of compound formulation of diabecron sustained-release pellet preparations, mix prepared compound metformin hydrochloride pioglitazone hydrochloride sustained-release pellet preparations with the pioglitazone hydrochloride sustained-release micropill, can reach and continue in vivo release and drug release behavior effect comparatively stably, stable its bioavailability that makes of drug release behavior improves relatively, the compound recipe combination of two kinds of micropills makes its better efficacy, and poisonous side effect of medicine reduces, and hypoglycemic effect is better.Within one day, be administered once and improved patient's compliance, for domestic and international diabetics provides better dosage regimen and curative effect.
Summary of the invention
The objective of the invention is in order to overcome deficiency of the prior art, a kind of compound formulation of diabecron sustained-release pellet preparations is provided, mix prepared compound metformin hydrochloride pioglitazone hydrochloride sustained-release pellet preparations with the pioglitazone hydrochloride sustained-release micropill, can effectively control medicine blood drug level, make blood drug level stable, and there is higher bioavailability, can improve clinical efficacy, reduce medicining times, can reach continual and steady blood sugar decreasing effect, can also improve compliance, reduce untoward reaction.
The present invention to achieve these goals, adopts following technical scheme: a kind of compound formulation of diabecron sustained-release pellet preparations, and the diabecron sustained-release micropill is by forming containing pill core and slow release layer two parts; Containing pill core, by metformin hydrochloride, filler, binding agent, formed; Slow release layer is comprised of slow-release material and porogen; The assembly percentage by weight is: metformin hydrochloride 40.0-70.0%, and filler 30.0-75.0%, binding agent 0.4-5.0%, slow-release material 4.7-16.7%, porogen 0.01-1.0%, above each component sum by weight ratio is 100%.
The assembly percentage by weight is: metformin hydrochloride 44.5-67.4%, microcrystalline Cellulose 23.0-66.0%, sucrose 11.3-18.5%, hypromellose 1.3-4.2%, the crylic acid resin aqueous dispersion is strange 5.3-14.2% especially, hypromellose 0.01-0.7%, above each component sum by weight ratio is 100%.
The assembly percentage by weight is: metformin hydrochloride 46.0-64.8%, microcrystalline Cellulose 43.0-72.6%, hypromellose 0.8-4.6%, Aquacoat product Sulisi 5.7-14.7%, sodium lauryl sulphate 0.01-0.6%, above each component sum by weight ratio is 100%.
The filler of buying from market is microcrystalline Cellulose, lactose, sucrose, starch " the wherein combination of one or more "; The binding agent of buying from market is hypromellose, polyvidone, carboxymethyl cellulose, methylcellulose, ethyl cellulose, Polyethylene Glycol, sucrose solution, sodium alginate, gelatin " the wherein combination of one or more "; The slow-release material of buying from market is especially strange, Aquacoat product Sulisi, cellulose acetate and matrix material " the wherein combination of one or more " of crylic acid resin aqueous dispersion; The porogen of buying from market is hypromellose, polyvinyl alcohol, sodium chloride, polyvidone, mannitol, lactose, sodium lauryl sulphate " the wherein combination of one or more ".
The invention has the beneficial effects as follows: the diameter that micropill is comprised of medicine and adjuvant is about the small entity of spherical shape of 1mm.Micropill belongs to polydisperse system, each dosage is usually containing tens or a hundreds of micropill, error or the defect of indivedual micropills in preparation is unlikely to the drug release behavior of whole preparation is affected greatly, because there is larger contact surface on medicine and gastrointestinal tract surface, absorb good and little to local zest, simultaneously, micropill is different from tablet, the former is not affected by the gastric emptying factor basically, therefore the infiltration rate of medicine is even, individual bioavailability difference is little; Micropill has the advantages such as particle diameter is even, good fluidity, difficult crushing, particularly the fine pellet core surface coatings, make location, slow release or controlled release preparation, technique is simple, can avoid other solid preparations as inhomogeneous as coatings such as tablets, may cause the risk of medicine pulse; The compound capsule formed by the micropill of different pharmaceutical, can increase medicine stability, improve curative effect, reduce poisonous side effect of medicine etc.
The metformin hydrochloride gastrointestinal absorbs rapidly, and metabolism is fast, and day medication dose is large and action time is short.Bioavailability is only 50-60%, Tmax 1-3 hour, and dosage increase to absorb reduces, and dosage is relevant without linearity to blood concentration, clinically is difficult to grasp dosage and effect; Take food and reduce absorbtivity and postpone peak time, the serum peak concentration reduces by 40%, necessary (medicine) being taken before meal use, and peak concentration changes greatly, and the patients with NIDDM of normal renal function and the patients with NIDDM of renal dysfunction can differ 1 times.Therefore be difficult to grasp dosage and effect; If make slow releasing preparation, drug release is slow, absorbs constantly, and dosage and blood drug level dependency are good, clinically is easy to grasp relation of dosage and effect.
The metformin hydrochloride water solublity is fabulous, the slow release layer coating material with Aquacoat product Sulisi (Surelease) as metformin hydrochloride, and while using separately, the rete permeance property of formation is better, and the drug release effect is steady.Therefore, control the release speed of medicine by regulating the coating film thickness, make the diabecron sustained-release micropill reach desirable drug release rate.
Metformin hydrochloride adds a certain proportion of lactose containing in pill core, can prevent from making to separate out the metformin hydrochloride crystal containing the pill wicking surface containing the extremely strong water solublity due to medicine in the pill core dry run.
Mix prepared compound metformin hydrochloride pioglitazone hydrochloride sustained-release pellet preparations with the pioglitazone hydrochloride sustained-release micropill, can reach and continue in vivo release and drug release behavior effect comparatively stably, stable its bioavailability that makes of drug release behavior improves relatively, the compound recipe combination of two kinds of micropills makes its better efficacy, poisonous side effect of medicine reduces, and hypoglycemic effect is better.Within one day, be administered once and improved patient's compliance, for domestic and international diabetics provides better dosage regimen and curative effect.
The specific embodiment
Below in conjunction with the specific embodiment, the present invention is described in further detail:
Embodiment 1
The diabecron sustained-release micropill is by forming containing pill core and slow release layer two parts; Containing pill core, by metformin hydrochloride, filler, binding agent, formed; Slow release layer is comprised of slow-release material and porogen; The assembly percentage by weight is: metformin hydrochloride 40.0-70.0%, and filler 30.0-75.0%, binding agent 0.4-5.0%, slow-release material 4.7-16.7%, porogen 0.01-1.0%, above each component sum by weight ratio is 100%.
Embodiment 2
The assembly percentage by weight is: metformin hydrochloride 44.5-67.4%, microcrystalline Cellulose 23.0-66.0%, sucrose 11.3-18.5%, hypromellose 1.3-4.2%, the crylic acid resin aqueous dispersion is strange 5.3-14.2% especially, hypromellose 0.01-0.7%, above each component sum by weight ratio is 100%.
Embodiment 3
The assembly percentage by weight is: metformin hydrochloride 46.0-64.8%, microcrystalline Cellulose 43.0-72.6%, hypromellose 0.8-4.6%, Aquacoat product Sulisi 5.7-14.7%, sodium lauryl sulphate 0.01-0.6%, above each component sum by weight ratio is 100%.
Embodiment 4
The filler of buying from market is microcrystalline Cellulose, lactose, sucrose, starch " the wherein combination of one or more "; The binding agent of buying from market is hypromellose, polyvidone, carboxymethyl cellulose, methylcellulose, ethyl cellulose, Polyethylene Glycol, sucrose solution, sodium alginate, gelatin " the wherein combination of one or more "; The slow-release material of buying from market is especially strange, Aquacoat product Sulisi, cellulose acetate and matrix material " the wherein combination of one or more " of crylic acid resin aqueous dispersion; The porogen of buying from market is hypromellose, polyvinyl alcohol, sodium chloride, polyvidone, mannitol, lactose, sodium lauryl sulphate " the wherein combination of one or more ".
The present invention is not limited to above compound formulation, and the mutual assembly between spice, all in protection scope of the present invention.
Claims (4)
1. the compound formulation of a diabecron sustained-release pellet preparations is characterized in that: the diabecron sustained-release micropill is by forming containing pill core and slow release layer two parts; Containing pill core, by metformin hydrochloride, filler, binding agent, formed; Slow release layer is comprised of slow-release material and porogen; The assembly percentage by weight is: metformin hydrochloride 40.0-70.0%, and filler 30.0-75.0%, binding agent 0.4-5.0%, slow-release material 4.7-16.7%, porogen 0.01-1.0%, above each component sum by weight ratio is 100%.
2. the compound formulation of a kind of diabecron sustained-release pellet preparations according to claim 1, it is characterized in that: the assembly percentage by weight is: metformin hydrochloride 44.5-67.4%, microcrystalline Cellulose 23.0-66.0%, sucrose 11.3-18.5%, hypromellose 1.3-4.2%, the crylic acid resin aqueous dispersion is strange 5.3-14.2% especially, hypromellose 0.01-0.7%, and above each component sum by weight ratio is 100%.
3. the compound formulation of a kind of diabecron sustained-release pellet preparations according to claim 1, it is characterized in that: the assembly percentage by weight is: metformin hydrochloride 46.0-64.8%, microcrystalline Cellulose 43.0-72.6%, hypromellose 0.8-4.6%, Aquacoat product Sulisi 5.7-14.7%, sodium lauryl sulphate 0.01-0.6%, above each component sum by weight ratio is 100%.
4. the compound formulation of a kind of diabecron sustained-release pellet preparations according to claim 1, is characterized in that: from the filler of market purchase, be microcrystalline Cellulose, lactose, sucrose, starch " the wherein combination of one or more "; The binding agent of buying from market is hypromellose, polyvidone, carboxymethyl cellulose, methylcellulose, ethyl cellulose, Polyethylene Glycol, sucrose solution, sodium alginate, gelatin " the wherein combination of one or more "; The slow-release material of buying from market is especially strange, Aquacoat product Sulisi, cellulose acetate and matrix material " the wherein combination of one or more " of crylic acid resin aqueous dispersion; The porogen of buying from market is hypromellose, polyvinyl alcohol, sodium chloride, polyvidone, mannitol, lactose, sodium lauryl sulphate " the wherein combination of one or more ".
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109330995A (en) * | 2018-12-05 | 2019-02-15 | 河北医科大学 | A kind of pellet and preparation method thereof containing short-acting antidiabetic drug |
| CN112451511A (en) * | 2020-12-31 | 2021-03-09 | 寿光富康制药有限公司 | Metformin hydrochloride preparation and preparation method thereof |
| CN113398097A (en) * | 2021-07-14 | 2021-09-17 | 南京康川济医药科技有限公司 | Dapagliflozin metformin sustained release preparation and preparation method thereof |
| CN113616624A (en) * | 2021-09-16 | 2021-11-09 | 南京康川济医药科技有限公司 | Empagliflozin metformin sustained release preparation and preparation method thereof |
| CN114469896A (en) * | 2020-10-26 | 2022-05-13 | 江苏万邦生化医药集团有限责任公司 | Metformin hydrochloride sustained-release empagliflozin hydrochloride quick-release pellet and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102716090A (en) * | 2012-01-05 | 2012-10-10 | 金陵药业股份有限公司 | Sustained-release metformin hydrochloride pellets and preparation method thereof |
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- 2013-08-26 CN CN2013103750698A patent/CN103417496A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102716090A (en) * | 2012-01-05 | 2012-10-10 | 金陵药业股份有限公司 | Sustained-release metformin hydrochloride pellets and preparation method thereof |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109330995A (en) * | 2018-12-05 | 2019-02-15 | 河北医科大学 | A kind of pellet and preparation method thereof containing short-acting antidiabetic drug |
| CN109330995B (en) * | 2018-12-05 | 2021-05-18 | 河北医科大学 | Pellet coated with short-acting hypoglycemic agent and preparation method thereof |
| CN114469896A (en) * | 2020-10-26 | 2022-05-13 | 江苏万邦生化医药集团有限责任公司 | Metformin hydrochloride sustained-release empagliflozin hydrochloride quick-release pellet and preparation method thereof |
| CN112451511A (en) * | 2020-12-31 | 2021-03-09 | 寿光富康制药有限公司 | Metformin hydrochloride preparation and preparation method thereof |
| CN113398097A (en) * | 2021-07-14 | 2021-09-17 | 南京康川济医药科技有限公司 | Dapagliflozin metformin sustained release preparation and preparation method thereof |
| CN113616624A (en) * | 2021-09-16 | 2021-11-09 | 南京康川济医药科技有限公司 | Empagliflozin metformin sustained release preparation and preparation method thereof |
| CN113616624B (en) * | 2021-09-16 | 2023-01-31 | 南京康川济医药科技有限公司 | Empagliflozin metformin sustained release preparation and preparation method thereof |
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Application publication date: 20131204 |