CN103054856A - Solid oral preparation containing metformin hydrochloride and atorvastatin calcium - Google Patents

Abstract

The invention discloses a solid oral preparation containing metformin hydrochloride and atorvastatin calcium. The solid oral preparation comprises metformin hydrochloride and atorvastatin calcium, wherein the weight ratio of the metformin hydrochloride to the atorvastatin calcium is (5-80): (250-1000); the solid oral preparation further comprises pharmaceutically acceptable excipients, wherein the weight ratio of the atorvastatin calcium to the excipients is 1: (2.3-9.6); and the excipients comprise one or more of starch, lactose, PVP (Polyvinyl Pyrrolidone), dextrin, microcrystalline cellulose, carboxymethyl cellulose, carboxymethyl starch sodium, hydroxypropyl cellulose, aerosol and magnesium stearate. The invention has the beneficial effects that the blood glucose and the blood lipids can be reduced synergistically, the cholesterol and triglyceride can be lowered while the blood glucose is reduced, the high-density lipoprotein (HDL) level in the blood can be increased, and the hypoglycemic and hypolipidemic effects can be improved, thereby correcting the metabolic syndrome of diabetics and reducing the long-term risk of cardiovascular and cerebrovascular diseases of the diabetics.

Description

The solid orally ingestible that contains metformin hydrochloride and Atorvastatin calcium

Technical field

The present invention relates to the pharmaceutical preparations technology field, particularly contain the solid orally ingestible of metformin hydrochloride and Atorvastatin calcium.

Background technology

Metformin hydrochloride is as one of common drug for the treatment of diabetes, it mainly passes through picked-up and the utilization of strong surrounding tissue to glucose, the anaerobic glycolysis of muscular tissue is increased, aerobic metabolism inconvenience, it concentrates on intestinal wall, suppresses glucose in the absorption of intestinal, suppresses glyconeogenesis, suppress the release of glucagon or the effect of inhibition insulin antagonist, and increase the sensitivity of insulin.Metformin hydrochloride class antidiabetic drug; not by stimulating beta Cell of islet to increase the concentration of insulin; but directly act on sugared metabolic process; promote the anerobic glycolysis of sugar; increase the peripheral tissues such as muscle, fat to picked-up and the utilization of glucose, thereby protect islet beta cell function in damaged condition to avoid further infringement.

Atorvastatin calcium is the selectivity that synthesizes in recent years, competitive 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, and effect for reducing fat is higher than other HMG-CoA reductase inhibitors.The non-activity of Atorvastatin calcium own, hydrolyzate after the oral absorption suppresses the rate-limiting enzyme HMG-CoA reductase in the cholesterol biosynthesis process in vivo competitively, make the synthetic minimizing of cholesterol, also make the synthetic increase of low density lipoprotein receptor, the Main Function position is at liver, the result reduces cholesterolemia and low-density lipoprotein cholesterol level, and moderate reduces serum triglyceride level and increases the blood hdl level.Thus to the control generation effect of atherosclerosis and coronary heart disease.

Summary of the invention

The object of the present invention is to provide a kind of can be at hypoglycemic while cholesterol reducing and triglyceride, and the solid orally ingestible that contains metformin hydrochloride and Atorvastatin calcium of the effect of rising blood middle-high density lipoprotein levels is arranged.

Purpose of the present invention is achieved through the following technical solutions: contain the solid orally ingestible of metformin hydrochloride and Atorvastatin calcium, it comprises Atorvastatin calcium and metformin hydrochloride, and the weight ratio of Atorvastatin calcium and metformin hydrochloride is:

Atorvastatin calcium 5～80,

Metformin hydrochloride 250～1000.

It also comprises pharmaceutically acceptable pharmaceutic adjuvant, the weight ratio of Atorvastatin calcium and adjuvant is 1:2.3～9.6, and described adjuvant comprises one or more in starch, lactose, PVP, dextrin, microcrystalline Cellulose, carmellose, carboxymethylstach sodium, hyprolose, micropowder silica gel, the magnesium stearate.

Described solid orally ingestible is capsule or tablet.

Each capsule or tablet contain Atorvastatin calcium 5mg～80mg, metformin hydrochloride 0.25g ~ 1g.

The described preparation method that contains the solid orally ingestible of metformin hydrochloride and Atorvastatin calcium, it may further comprise the steps:

S1, take by weighing metformin hydrochloride, Atorvastatin calcium and adjuvant by above-mentioned weight ratio, metformin hydrochloride, Atorvastatin calcium are crossed 100 mesh sieves, and adjuvant is crossed 80 mesh sieves;

S2, with the component mix homogeneously of removing in metformin hydrochloride, Atorvastatin calcium and the adjuvant outside PVP, micropowder silica gel and the magnesium stearate; The PVP that takes by weighing is mixed with 5% solution with pure water, and it is sprayed into the said mixture material as binding agent, be mixed to do and wet evenly, granulate with 16 ~ 24 mesh sieves;

S3, be dried to moisture below 5%, add the micropowder silica gel and the magnesium stearate that take by weighing, and mix homogeneously, be pressed into sheet or the encapsulated solid orally ingestible that contains metformin hydrochloride and Atorvastatin calcium that namely gets.

The present invention has the following advantages: of the present invention can be at hypoglycemic while cholesterol reducing and triglyceride, and the effect of rising blood middle-high density lipoprotein levels is arranged; Improve blood sugar lowering, effect for reducing blood fat, be used for correcting the metabolism syndrome of diabetics, be conducive to reduce the cardiovascular and cerebrovascular disease danger at a specified future date of diabetics.

The specific embodiment

The present invention will be further described below in conjunction with embodiment, and protection scope of the present invention is not limited to the following stated:

Embodiment 1:

The solid orally ingestible that contains metformin hydrochloride and Atorvastatin calcium can be tablet or capsule, and it comprises that following component and per 1000 (grain) consumptions of each component are:

Metformin hydrochloride 250g,

Atorvastatin calcium 5g,

Adjuvant 48g,

Described adjuvant comprises following component, and the consumption of each component is:

Starch 10g,

Lactose 10g,

Microcrystalline Cellulose 10g,

Hyprolose 10g,

PVPK series 5g,

Magnesium stearate 3g.

Above-mentioned metformin hydrochloride quality meets two ones of CP2010 versions, and Atorvastatin calcium meets WS-(X-127)-2003Z.

Contain the preparation method of the solid orally ingestible of metformin hydrochloride and Atorvastatin calcium, it may further comprise the steps:

S1, take by weighing metformin hydrochloride, Atorvastatin calcium and adjuvant by above-mentioned prescription, metformin hydrochloride, Atorvastatin calcium are crossed 100 mesh sieves, and adjuvant is crossed 80 mesh sieves;

S2, with the component mix homogeneously of removing in metformin hydrochloride, Atorvastatin calcium and the adjuvant outside PVP, micropowder silica gel and the magnesium stearate; The PVP that takes by weighing is mixed with 5% solution with pure water, and it is sprayed into the said mixture material as binding agent, be mixed to do and wet evenly, granulate with 16 ~ 24 mesh sieves;

S3, be dried to moisture below 5%, add the micropowder silica gel and the magnesium stearate that take by weighing, and mix homogeneously, be pressed into sheet or the encapsulated solid orally ingestible that contains metformin hydrochloride and Atorvastatin calcium that namely gets.

Embodiment 2:

The solid orally ingestible that contains metformin hydrochloride and Atorvastatin calcium can be tablet or capsule, and it comprises that following component and per 1000 (grain) consumptions of each component are:

Metformin hydrochloride 500g,

Atorvastatin calcium 10g,

Adjuvant 95g,

Described adjuvant comprises following component, and the consumption of each component is:

Starch 20g,

Lactose 20g,

Microcrystalline Cellulose 20g,

Carboxymethylstach sodium 20g,

PVPK series 10g,

Micropowder silica gel 5g.

Above-mentioned metformin hydrochloride quality meets two ones of CP2010 versions, and Atorvastatin calcium meets WS-(X-127)-2003Z.

Contain the preparation method of solid orally ingestible of metformin hydrochloride and Atorvastatin calcium with embodiment 1.

Embodiment 3:

The solid orally ingestible that contains metformin hydrochloride and Atorvastatin calcium can be tablet or capsule, and it comprises that following component and per 1000 (grain) consumptions of each component are:

Metformin hydrochloride 1000g,

Atorvastatin calcium 80g,

Adjuvant 185g,

Described adjuvant comprises following component, and the consumption of each component is:

DEXTRIN g,

Lactose 40g,

Microcrystalline Cellulose 40g,

Carboxymethylstach sodium 20g,

Hydroxyl methylcellulose 20g,

PVPK series 15g,

Micropowder silica gel 5g,

Magnesium stearate 5g.

Above-mentioned metformin hydrochloride quality meets two ones of CP2010 versions, and Atorvastatin calcium meets WS-(X-127)-2003Z.

Contain the preparation method of solid orally ingestible of metformin hydrochloride and Atorvastatin calcium with embodiment 1.

The present invention will be further described below in conjunction with test:

Animal: 90 of healthy SD male rats, body weight 200g ± 20g

Experimental animal feedstuff: 1, normal feedstuff;

2, high lipid food: self-control forms: Adeps Sus domestica 30%+ cholesterol 1%+ normal feedstuff 69%, and the cholesterol addition is 149.5mg/kg;

3, alloxan aqueous solution 10mg/ml (PH3) faces and uses new system.

Medicine: 1, the solid orally ingestible that contains metformin hydrochloride and Atorvastatin calcium of the present invention;

2, commercially available metformin hydrochloride tablet (glucophage, specification 0.5g, every heavy 0.53g, lot number: 1104090, Sino-U.S. executes in Shanghai expensive precious pharmaceutical Co. Ltd) and commercially available atorvastatin (lipitor, specification 20mg, every heavy 0.16g, lot number: 038711K, lot number of the repackaged products: 1137057, pfizer inc).

Instrument and reagent: 1, triglyceride determination test kit, No. the 2400362nd, Beijing Kinghawk Pharmaceutical Co., Ltd.'s capital medicine prison tool (standard) word 2006.

2, No. the 2400356th, cholesterol determination test kit Beijing Kinghawk Pharmaceutical Co., Ltd. capital medicine prison tool (standard) word 2006.

3, stable blood glucose meter (No. the 2400069th, Hunan food medicine prison tool (standard) word 2008, unit special use BIDI28F0068) with test strip for blood-sugar (No. the 2400070th, Hunan food medicine prison tool (standard) word 2008, lot number: 2226NC), Changsha Sinocare Inc..

Experimental technique:

1, modeling

Rat is divided into the high sugared model group (n=80) of high fat, blank group (n=10) at random, the high sugared model group of high fat is pressed 100mg/kg lumbar injection alloxan every day, and (alloxan is by destroying insulin β cell, make cell DNA impaired, and the activity of activation adenosine diphosphate ribose body synzyme, make the cozymase content decrease, finally cause insulin deficit, make metabolism disorder, blood sugar increasing.), raise simultaneously with high lipid food; The blank group is raised with normal diet.Raised for 13 weeks continuously.

After continuously raising for 4 weeks, by U.S. diabetic complication model association (AMDCC) proposed standard, fasting 6 hours: 7 of mornings are got the blood point: get the about 0.4ml mensuration of ophthalmic corner of the eyes vein peripheral blood after the anesthesia to point at noons 13.Require: blood glucose (Glu) 11.1mmol/l is considered as the modeling success, has 81 modelings successes.

2, test

The rat of modeling success is divided into embodiment of the invention group, metformin hydrochloride group, Atorvastatin calcium group at random, the above-mentioned still conduct blank of blank group of modeling of not implementing is to group, raise with normal diet, embodiment of the invention group, metformin hydrochloride group, Atorvastatin calcium group, when continuing to raise with high lipid food, give respectively embodiment of the invention compositions, metformin hydrochloride tablet, atorvastatin, fed for 3 weeks continuously, each group is freely drunk water, itemized record are respectively organized daily ingestion amount, routine weighing in the process of the test.12h freely drinks water on an empty stomach before putting to death, and weighs, and the eye socket posterior vein is got hematometry.

Medication:

1 group of the embodiment of the invention: give simultaneously the solid orally ingestible that contains metformin hydrochloride and Atorvastatin calcium that embodiment 1 makes raising with high fat beverage, press the 60mg/kg rat body weight.

2 groups of the embodiment of the invention: give simultaneously the solid orally ingestible that contains metformin hydrochloride and Atorvastatin calcium that embodiment 2 makes raising with high fat beverage, press the 60mg/kg rat body weight.

3 groups of the embodiment of the invention: give simultaneously the solid orally ingestible that contains metformin hydrochloride and Atorvastatin calcium that embodiment 3 makes raising with high fat beverage, press the 60mg/kg rat body weight.

Metformin hydrochloride group: give simultaneously metformin hydrochloride tablet raising with high fat beverage, press the 53mg/kg rat body weight.

Atorvastatin group: give simultaneously Atorvaststin (lipitor) raising with high fat beverage, press the 8mg/kg rat body weight.

Results and analysis:

The invention compositions is on the impact of triglyceride in the rat blood serum (TG) and serum total cholesterol (TC), and result and analysis see the following form.

Annotate: refer to the index that records after the modeling in the table before the test, refer to medicine feed data measureds after 3 weeks after the test.

Above experimental data shows: the present composition (experimental example 1～3) test group and metformin hydrochloride group and Atorvastatin calcium group more all there are differences, P＜0.01, significant difference is arranged, illustrate that subject composition has synergism to blood sugar lowering, blood fat reducing.

Claims (5)

1. contain the solid orally ingestible of metformin hydrochloride and Atorvastatin calcium, it is characterized in that: it comprises Atorvastatin calcium and metformin hydrochloride, and the weight ratio of Atorvastatin calcium and metformin hydrochloride is:

Atorvastatin calcium 5～80,

Metformin hydrochloride 250～1000.

2. the solid orally ingestible that contains metformin hydrochloride and Atorvastatin calcium according to claim 1, it is characterized in that: it also comprises pharmaceutically acceptable pharmaceutic adjuvant, the weight ratio of Atorvastatin calcium and adjuvant is 1:2.3～9.6, and described adjuvant comprises one or more in starch, lactose, PVP, dextrin, microcrystalline Cellulose, carmellose, carboxymethylstach sodium, hyprolose, micropowder silica gel, the magnesium stearate.

3. the solid orally ingestible that contains metformin hydrochloride and Atorvastatin calcium according to claim 1, it is characterized in that: described solid orally ingestible is capsule or tablet.

4. the solid orally ingestible that contains metformin hydrochloride and Atorvastatin calcium according to claim 3, it is characterized in that: each capsule or tablet contain Atorvastatin calcium 5mg～80mg, metformin hydrochloride 0.25g ~ 1g.

5. the preparation method that contains the solid orally ingestible of metformin hydrochloride and Atorvastatin calcium as claimed in claim 2, it is characterized in that: it may further comprise the steps:

S1, take by weighing metformin hydrochloride, Atorvastatin calcium and adjuvant by above-mentioned weight ratio, metformin hydrochloride, Atorvastatin calcium are crossed 100 mesh sieves, and adjuvant is crossed 80 mesh sieves;

S2, with the component mix homogeneously of removing in metformin hydrochloride, Atorvastatin calcium and the adjuvant outside PVP, micropowder silica gel and the magnesium stearate; The PVP that takes by weighing is mixed with 5% solution with pure water, and it is sprayed into the said mixture material as binding agent, be mixed to do and wet evenly, granulate with 16 ~ 24 mesh sieves;

S3, be dried to moisture below 5%, add the micropowder silica gel and the magnesium stearate that take by weighing, and mix homogeneously, be pressed into sheet or the encapsulated solid orally ingestible that contains metformin hydrochloride and Atorvastatin calcium that namely gets.