CN112641776A - A pharmaceutical composition containing metformin or its pharmaceutically acceptable salt and Alogliptin or its pharmaceutically acceptable salt as active ingredients - Google Patents
A pharmaceutical composition containing metformin or its pharmaceutically acceptable salt and Alogliptin or its pharmaceutically acceptable salt as active ingredients Download PDFInfo
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- CN112641776A CN112641776A CN201910970183.2A CN201910970183A CN112641776A CN 112641776 A CN112641776 A CN 112641776A CN 201910970183 A CN201910970183 A CN 201910970183A CN 112641776 A CN112641776 A CN 112641776A
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- pharmaceutical composition
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- hydrochloride
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Abstract
The invention discloses a medicinal composition taking metformin or medicinal salt thereof and augmentin or medicinal salt thereof as active ingredients. Pharmacological research results show that the medicinal composition of metformin hydrochloride and alogliptin hydrochloride can improve the islet morphology of experimental animals, effectively reduce the blood sugar level of diabetes model animals, improve the glucose tolerance, and reduce the glucose, and the glucose reduction effect shows dose correlation, and the glucose reduction effect is rapid, stable and lasting.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a pharmaceutical composition containing metformin or pharmaceutically acceptable salts thereof and augustine or pharmaceutically acceptable salts thereof.
Background
Diabetes is a group of metabolic diseases characterized by hyperglycemia. Hyperglycemia is caused by a defect in insulin secretion or an impaired biological action, or both. The chronic hyperglycemic state of diabetes is significantly associated with long-term complications, namely damage, dysfunction and failure of numerous organs, particularly the kidneys, eyes, nerves, heart and blood vessels, etc. The complex treatment of diabetes should not only aim at lowering blood glucose to near normal levels, but also actively correct metabolic abnormalities and reduce cardiovascular risk factors.
Diabetes is currently defined according to the WHO/ADA standard, i.e., symptoms of diabetes plus random plasma glucose levels of 11.1mmol/L or more, or fasting plasma glucose levels of 7.0mmol/L or 11.1mmol/L or more 2-h after a 75g anhydrous glucose load in the oral glucose tolerance test. In the absence of typical symptoms of diabetes, diabetes cannot be diagnosed by only one blood glucose measurement, and must be diagnosed after confirmation every other day.
Diabetes has become the third disease after cardiovascular and malignant tumors seriously endangering human health. A 'national diabetes epidemiological survey (2007 + 2008)' shows that in the population over 20 years old in China, the prevalence rates of diabetes of men and women reach 10.6% and 8.8% respectively, and the prevalence rate of diabetes is 9.7% overall, so that the total population of diabetes in the country is estimated to be about 9200 thousands of people, and the country with the most diabetes patients in the world is obtained.
Diabetes can be classified into type I diabetes and type II diabetes according to the pathological characteristics. Type ii diabetes is also known as adult onset diabetes, which is frequently encountered in the elderly population. Accounts for more than 90 percent of the patients with diabetes at present. Type ii diabetes is a complex metabolic disorder known in part to the pathogenesis today. It is clinically manifested by impaired insulin function and abnormal hepatic glycogen metabolism. Type ii diabetes can be properly controlled in its early stages by dietary control and exercise, but over time, its glycemic control tends to worsen. Therefore, when diet control and exercise can not be controlled, related hypoglycemic drugs are used for control.
Metformin hydrochloride is a biguanide hypoglycemic drug, is an oral antihyperglycemic drug widely used in various countries in the world at present, can improve the tolerance of type II diabetes patients to sugar, and reduce the basic and postprandial plasma glucose concentration. Metformin hydrochloride does not promote insulin secretion, and the hypoglycemic effect of metformin hydrochloride mainly aims at promoting glucose uptake by adipose tissues, increasing anaerobic glycolysis of muscle tissues, increasing the utilization of glucose and reducing the absorption of glucose through the digestive tract.
Dipeptidyl peptidase IV (DPP-IV) inhibitors, also known as incretin enhancers, reduce the degradation rate of glucagon-like peptide I GLP-1 by inhibiting the activity of DPP-IV, further stimulate the secretion of insulin at high blood glucose concentration, and exert the function of resisting type II diabetes by delaying gastric emptying, inhibiting glucagon release, promoting the proliferation and differentiation of islet beta cells, enhancing satiety and the like. And has no obvious influence on the body weight.
Numerous DPP-IV inhibitors are disclosed in the literature and patents, and the DPP-IV inhibitors sitagliptin (MK-0431) and vildagliptin (LAF-237) are currently marketed in the United states and Europe for the treatment of type II diabetes, respectively. However, the inhibitory activity of these DPP-IV inhibitors on dipeptidyl peptidase in the prior art is not satisfactory, and the activity is not as strong as metformin [ Medicinal Research Review,2009,29(1),125-195 ].
Because the insulin effect in the body of the type II diabetes mellitus shows the trend of worsening along with the increase of time, the hypoglycemic medicine with higher activity is correspondingly needed to be adopted for controlling the blood sugar.
Augliptin (Augliptin) is a novel dipeptidyl peptidase (DPP-IV) inhibitor, and has the following chemical structural formula:
the chemical name is: (R) -3-amino-1- ((3aS,6aS) -5- (2-fluoro-2-methylpropanoyl) -hexahydropyrrolo [3,4-b ] pyrrol-1 (2H) -yl) -4- (2,4, 5-trifluorophenyl) -1-butanone. The glucose-dependent mechanism of action of augmentin is different from that of sulfonylurea drugs. Auogliptin is a potent and highly selective DPP-4 enzyme inhibitor that does not inhibit DPP-8, DPP-9 or FAP closely related to DPP-4 at therapeutic concentrations.
In the prior art, no research report on the combination of the Australian gliptin and other hypoglycemic drugs exists.
Disclosure of Invention
The invention aims to provide a medicinal composition for treating type II diabetes, which takes metformin or pharmaceutically acceptable salts thereof and augustine or pharmaceutically acceptable salts thereof as active ingredients, and further can comprise pharmaceutically acceptable auxiliary materials.
The pharmaceutically acceptable salts of metformin and augmentin are acid salts including acetate, adipate, aspartate, benzoate, benzenesulfonate, bisulfate/sulfate, borate, camphorsulfonate, citrate, cyclamate, edisylate, ethanesulfonate, formate, fumarate, gluconate, glucuronate, hexafluorophosphate, oxybenzoyl benzoate, hydrochloride/chloride, hydrobromide/bromide, hydroiodide/iodide, isethionate, lactate, malate, maleate, malonate, methanesulfonate, methylsulfate, naphthenate, 2-naphthalenesulfonate, nicotinate, nitrate, orotate, oxalate, palmitate, pamoate, phosphate/biphosphate/dihydrogenphosphate, pyroglutamate, glutamate, dihydrogenphosphate, dihydrogensulfate, dihydrogensulfonate, Saccharic acid salt, stearic acid salt, succinic acid salt, tannic acid salt, tartaric acid salt, toluenesulfonic acid salt, trifluoroacetic acid salt, xinafoate salt and the like, and preferably metformin hydrochloride and augmentin hydrochloride.
The main form of the pharmaceutical composition of the present invention is an oral preparation. The oral preparation comprises any one solid oral dosage form of tablets, capsules, granules, dispersible tablets, chewable tablets, effervescent tablets and effervescent granules. Among them, tablets and capsules are preferable.
The content of active ingredients in the medicinal composition is 520mg-1050 mg/unit dose of the medicinal composition, wherein the unit preparation content of the metformin hydrochloride is 500mg-1000mg, and the unit preparation content of the alogliptin hydrochloride is 20mg-50 mg. For the medicinal composition of metformin hydrochloride and augustine hydrochloride, the mass ratio of metformin hydrochloride to augustine hydrochloride is preferably 20-50: 1. a particularly preferred combination of unit doses for oral formulations is metformin hydrochloride + augustine hydrochloride: 500mg +25mg, 850mg +25mg, 1000mg +25 mg.
The pharmaceutical compositions of the present invention are suitable for:
(1) treatment of type II diabetes where blood glucose cannot be controlled by diet and exercise.
(2) The metformin hydrochloride or DPP-IV inhibitor drugs are taken alone, and the treatment effect is not ideal or the type II diabetes mellitus which cannot be controlled is treated.
Detailed Description
The metformin hydrochloride and alogliptin hydrochloride preparations of the present invention are further specifically illustrated by the following examples, but are not limited to the following examples.
Example 1 metformin hydrochloride and Alogliptin hydrochloride tablets
The preparation method comprises the following steps:
respectively sieving metformin hydrochloride and alogliptin hydrochloride with a 60-mesh sieve, uniformly mixing metformin hydrochloride, hydroxypropyl cellulose and alogliptin hydrochloride, granulating and drying by using a fluidized bed, sieving with a 30-mesh sieve, granulating, adding magnesium stearate, uniformly mixing, and pressing into tablets by using a proper die.
Selecting appropriate coating material for the tablet obtained by above compression to obtain coated tablet, which can be film coated tablet, enteric coated tablet, etc.
Example 2 metformin hydrochloride and Alogliptin hydrochloride capsules
The preparation method comprises the following steps:
respectively sieving metformin hydrochloride and alogliptin hydrochloride with a 60-mesh sieve, uniformly mixing metformin hydrochloride, hydroxypropyl cellulose and alogliptin hydrochloride, granulating and drying by using a fluidized bed, sieving with a 30-mesh sieve, granulating, adding magnesium stearate, uniformly mixing, and filling to obtain the compound preparation.
The capsule shell for filling is a common capsule shell.
EXAMPLE 3 dispersible tablets of metformin hydrochloride and Alogliptin hydrochloride
The preparation method comprises the following steps:
respectively sieving metformin hydrochloride, alogliptin hydrochloride and microcrystalline cellulose with a 80-mesh sieve, uniformly mixing, adding 75% ethanol solution to prepare soft materials, sieving with a 20-mesh sieve, granulating, drying, and sieving with a 20-mesh sieve for size stabilization. Adding the rest adjuvants, mixing, and making into tablet by using a suitable punch die.
Example 4 pharmacological experimental studies of the invention demonstrate the applicability and advantages of the pharmaceutical compositions of the invention.
1. In vitro enzyme inhibitory Activity test
Reference is made to the methods disclosed in J.Med.chem.2006,49, 3520-: the recombinant proteins of DPP-4, DPP-7, DPP-8, DPP-9 and FAP are obtained by expression by using an insect expression system. The inhibitory effect of the 5 enzymes described above was evaluated by means of fluorogenic substrate detection on the inhibition of metformin hydrochloride and of a pharmaceutical composition with a unit dose of augmentin hydrochloride of 850mg +25 mg. The positive reference medicament adopted simultaneously is a medicinal composition with the unit dosage of the metformin hydrochloride and the vildagliptin (LAF237) of 850mg +25 mg.
TABLE 1 pharmaceutical IC on 5 dipeptidases50Value (μ M)
In vitro test results show that IC of metformin hydrochloride and Alogliptin on DPP-450The value was 0.024. + -. 0.002. mu.M. The selectivity of the inhibition intensity to the inhibition activity of other dipeptidases is more than 250 times, and the selectivity to DPP-4 is obviously better than that of other dipeptidase family members.
2. The experimental method comprises the following steps: establishing a diabetic rat model: adult Wistar rats were selected and used to prepare Streptozotocin (STZ) solution with a concentration of 10mg/ml in an experiment using 0.01 mmol.L citrate buffer solution with a pH of 4.5. After fasting the rats for 16h, the rats were weighed and injected intraperitoneally once with the streptozotocin solution described above at a rate of 55mg per kg. After 7 days, blood was taken from orbital veins of rats to measure blood glucose values. Selecting diabetic mice with fasting blood glucose of more than or equal to 11.11 mmol/L. Selecting a compound tablet of metformin hydrochloride and augmentin prepared by the method (the ratio of metformin hydrochloride to augmentin is 850 mg: 25mg) according to the weight, wherein the compound tablet is a model group of the augmentin which the weight is 10.5mg/kg, 35mg/kg and 105mg/kg, the augmentin which the weight is 3mg/kg, the augmentin which the weight is 102mg/kg, the augmentin group of the metformin hydrochloride, and weighing the weight of each 3 days for an empty control group (normal rat), a model control group (diabetic rat), the model group, the metformin group and the augmentin group, measuring the blood sugar every 4 weeks and observing the change of pancreatic islets timely. And observing the oral glucose tolerance of normal rats simultaneously, the following results were obtained:
(1) metformin hydrochloride and alogliptin compound tablets (metformin hydrochloride and alogliptin ratio is 850 mg:
25mg) can effectively reduce the blood sugar level of diabetes model animals, improve the glucose tolerance, and the blood sugar reduction effect shows dose correlation. Single gavage administration also significantly reduced the area under the oral glucose tolerance curve AUC (p <0.01-0.001) in normal rats, and there was a dose correlation. Compared with a control group, the compound tablet with the dosage of 105mg/kg can obtain the treatment effect with statistical difference, and shows strong hypoglycemic activity; 105mg/kg was regarded as the optimum pharmacodynamic dose.
(2) For diabetes model animals, multiple administrations of the compound tablet of metformin hydrochloride and augmentin at each dose can improve the islet morphology of the experimental animals, increase the islet volume and clear the boundary. The effect is probably effective in reducing blood sugar with the augmentin and reducing the damage of a high-sugar environment to beta cells; simultaneously, the activity of DPP-4 enzyme is inhibited, the degradation of GLP-1 is inhibited, and the functions of GLP-1 stimulating the proliferation and differentiation of beta cells and inhibiting the apoptosis of the beta cells are exerted.
(3) The metformin hydrochloride and the augustine have quick hypoglycemic effect and low risk of hypoglycemia.
For normal rats, the metformin hydrochloride and the compound tablet of the augmentin have no effect of reducing fasting blood glucose 15min, 30min, 2h and 4h after intragastric administration, and have no statistical difference compared with the administration before and after the administration. Under the stimulation of glucose, the activity of DPP-4 in plasma can be obviously reduced after a compound tablet of metformin hydrochloride and augmentin is subjected to single intragastric administration for 15min, so that the area AUC (p is less than 0.01-0.001) under the oral glucose tolerance curve of normal rats is obviously reduced. The compound tablet of metformin hydrochloride and augustine has no hypoglycemic effect on normal rats under the condition of no glucose stimulation.
(4) The comparison of the compound metformin hydrochloride and the alogliptin hydrochloride to the blood sugar of the diabetic rats is shown in the following table:
TABLE 2 Effect of the Compound preparation on blood glucose in diabetic rats (n 15)
As can be seen from Table 2, after the compound metformin hydrochloride and Auogliptin hydrochloride are used for treatment, the fasting blood sugar of the diabetic rats is remarkably reduced, and the blood sugar reducing effect is rapid, stable and lasting.
(5) The compound metformin hydrochloride and alogliptin can inhibit the body weight reduction trend of diabetes mellitus after being used for a plurality of times and for a long time, and adverse reactions of weight increase can not occur.
TABLE 3 weight effect of the combination preparation on diabetic rats (n 15)
The streptozotocin induced diabetes model rats are administrated by gavage for 1 time every day and are continuously administrated for 2 months, the weight of the diabetes model rats is obviously lower than that of the diabetes model rats, and the weight of the diabetes model rats is in a descending trend along with the prolonging of the disease course (P is less than 0.01). The weight of the diabetic rats can be recovered after the compound preparation is administered. The results of the pharmacokinetic studies accompanied with the long-term toxicity test of the rat gavage drug administration show that: the compound preparation is administrated to rats by intragastric administration for 1 time every day for 1 month continuously, and the in vivo exposure amount of the medicine is not obviously different from that of the first administration, which shows that the compound metformin hydrochloride and the alogliptin do not generate obvious accumulation in vivo, the influence on the body weight is neutral, and no adverse reaction of weight gain is caused.
Claims (9)
1. A pharmaceutical composition for treating type II diabetes mellitus, which comprises metformin or a pharmaceutically acceptable salt thereof and alogliptin or a pharmaceutically acceptable salt thereof as active ingredients.
2. The pharmaceutical composition of claim 1, further comprising a pharmaceutically acceptable excipient.
3. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable salt of metformin is metformin hydrochloride, the pharmaceutically acceptable salt of alogliptin is alogliptin hydrochloride, and the active ingredient content of the pharmaceutical composition is 520mg to 1050mg per unit dose.
4. The pharmaceutical composition according to claim 3, wherein the metformin hydrochloride is present in a unit dose of 500mg to 1000 mg.
5. The pharmaceutical composition of claim 3, wherein the amount of the alogliptin hydrochloride is from 20mg to 50mg per unit dose of the pharmaceutical composition.
6. The pharmaceutical composition according to claim 3, wherein the mass ratio of metformin hydrochloride to alogliptin hydrochloride is 20-50: 1.
7. the pharmaceutical composition of claim 1, wherein the pharmaceutical composition is an oral formulation.
8. The pharmaceutical composition of claim 7, wherein the oral formulation is selected from the group consisting of tablets, capsules, and granules.
9. Use of a pharmaceutical composition according to any one of claims 1 to 8 in the manufacture of a medicament for the treatment of type ii diabetes, including type ii diabetes where blood glucose cannot be controlled by diet or exercise and type ii diabetes where the monotherapy with metformin or a pharmaceutically acceptable salt thereof or augmentin or a pharmaceutically acceptable salt thereof is not effective.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114349665A (en) * | 2021-11-30 | 2022-04-15 | 青岛博创生物科学研究院 | Metformin pyroglutamic acid crystal and preparation method and application thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101181264A (en) * | 2007-11-27 | 2008-05-21 | 北京润德康医药技术有限公司 | Pharmaceutical composition taking metformin hydrochloride and vigelegting as active component as well as preparing method and uses thereof |
| CN101234105A (en) * | 2008-01-09 | 2008-08-06 | 北京润德康医药技术有限公司 | Pharmaceutical composition containing diabetosan and vildagliptin and preparation thereof |
| CN102266325A (en) * | 2011-07-28 | 2011-12-07 | 海南锦瑞制药股份有限公司 | Melbine crystal and medicinal composition of melbine and saxagliptin and preparation method thereof |
| CN103655570A (en) * | 2013-12-11 | 2014-03-26 | 深圳翰宇药业股份有限公司 | Sitagliptin and melbine compound sustained-release preparation and preparation method thereof |
| WO2014187343A1 (en) * | 2013-05-22 | 2014-11-27 | 四川海思科制药有限公司 | Benzofuran derivative, preparation method therefor, and medical application thereof |
| CN104884051A (en) * | 2012-10-08 | 2015-09-02 | 株式会社Lg生命科学 | Combination drug comprising gemigliptin and metformin, and method for the preparation thereof |
-
2019
- 2019-10-12 CN CN201910970183.2A patent/CN112641776A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101181264A (en) * | 2007-11-27 | 2008-05-21 | 北京润德康医药技术有限公司 | Pharmaceutical composition taking metformin hydrochloride and vigelegting as active component as well as preparing method and uses thereof |
| CN101234105A (en) * | 2008-01-09 | 2008-08-06 | 北京润德康医药技术有限公司 | Pharmaceutical composition containing diabetosan and vildagliptin and preparation thereof |
| CN102266325A (en) * | 2011-07-28 | 2011-12-07 | 海南锦瑞制药股份有限公司 | Melbine crystal and medicinal composition of melbine and saxagliptin and preparation method thereof |
| CN104884051A (en) * | 2012-10-08 | 2015-09-02 | 株式会社Lg生命科学 | Combination drug comprising gemigliptin and metformin, and method for the preparation thereof |
| WO2014187343A1 (en) * | 2013-05-22 | 2014-11-27 | 四川海思科制药有限公司 | Benzofuran derivative, preparation method therefor, and medical application thereof |
| CN103655570A (en) * | 2013-12-11 | 2014-03-26 | 深圳翰宇药业股份有限公司 | Sitagliptin and melbine compound sustained-release preparation and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| R. RAVI SHANKAR ET AL.: "A randomized clinical trial evaluating the efficacy and safety of the once-weekly dipeptidyl peptidase-4 inhibitor omarigliptin in patients with type 2 diabetes inadequately controlled on metformin monotherapy", 《 CURRENT MEDICAL RESEARCH AND OPINION》 * |
| 母义明等: "DPP-4抑制剂利格列汀的疗效与安全性评价", 《药品评价》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114349665A (en) * | 2021-11-30 | 2022-04-15 | 青岛博创生物科学研究院 | Metformin pyroglutamic acid crystal and preparation method and application thereof |
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