CN101234105A - Pharmaceutical composition containing diabetosan and vildagliptin and preparation thereof - Google Patents
Pharmaceutical composition containing diabetosan and vildagliptin and preparation thereof Download PDFInfo
- Publication number
- CN101234105A CN101234105A CNA2008100558154A CN200810055815A CN101234105A CN 101234105 A CN101234105 A CN 101234105A CN A2008100558154 A CNA2008100558154 A CN A2008100558154A CN 200810055815 A CN200810055815 A CN 200810055815A CN 101234105 A CN101234105 A CN 101234105A
- Authority
- CN
- China
- Prior art keywords
- vildagliptin
- pharmaceutical composition
- metformin
- metformin hydrochloride
- tablet
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 title claims abstract description 34
- 229960001254 vildagliptin Drugs 0.000 title claims abstract description 34
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 title claims description 26
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 17
- 238000002360 preparation method Methods 0.000 title abstract description 12
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims abstract description 43
- 239000000203 mixture Substances 0.000 claims abstract description 28
- 239000008187 granular material Substances 0.000 claims abstract description 13
- 239000002775 capsule Substances 0.000 claims abstract description 7
- 239000003826 tablet Substances 0.000 claims abstract description 7
- 239000007910 chewable tablet Substances 0.000 claims abstract description 4
- 239000007919 dispersible tablet Substances 0.000 claims abstract description 4
- 239000007938 effervescent tablet Substances 0.000 claims abstract description 4
- 239000006189 buccal tablet Substances 0.000 claims abstract description 3
- 238000002156 mixing Methods 0.000 claims abstract description 3
- 229960004329 metformin hydrochloride Drugs 0.000 claims description 26
- 150000001875 compounds Chemical class 0.000 claims description 14
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 9
- 238000009472 formulation Methods 0.000 claims description 8
- 229940068682 chewable tablet Drugs 0.000 claims description 3
- 235000005911 diet Nutrition 0.000 claims description 3
- 230000037213 diet Effects 0.000 claims description 3
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- 229960003105 metformin Drugs 0.000 abstract description 16
- 238000000034 method Methods 0.000 abstract description 6
- 239000000463 material Substances 0.000 abstract description 5
- 229940035752 metformin and vildagliptin Drugs 0.000 abstract description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 abstract 3
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- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 16
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 11
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Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to medical composition containing metformin and Vildagliptin and a preparation method thereof. The medical composition is formed by taking metformin chloride and Vildagliptin as medical active components and blending with pharmaceutically acceptable auxiliary materials; the invention adopts the metformin chloride and Vildagliptin as materials and adds auxiliary materials with some special kinds and proportions to prepare and develop diversified oral preparations such as tablets, capsules, granules, dispersible tablets, chewable tablets, buccal tablets, effervescent tablets, effervescent granules according to the technical method of the invention. The medical composition of the invention can be used for treating diabetes type II that can not be properly cured by alimentary control and sports and also for diabetes type II that can not be controlled by simply using metformin chloride or Vildagliptin.
Description
Technical field
The present invention relates to a kind of is Pharmaceutical composition of active component and preparation method thereof, purposes with metformin hydrochloride and vildagliptin, belongs to medical technical field.
Background technology
Diabetes (Diabetes mellitus) be since a kind of syndrome of the caused glucose of cellular metabolism effect defective, protein and the lipid metabolic disorder of insufficient insulin or insulin along with the fall ill prolongation of time of diabetes, the intravital metabolism disorder of body is controlled well as can not get, the chronic complicating diseases that can cause tissues such as eye, kidney, nerve, blood vessel and heart, organ, so that final take place blind, lower limb are gangrenous, uremia, apoplexy or myocardial infarction, even threat to life.Diabetes are a kind of commonly encountered diseases, and along with growth in the living standard, the sickness rate of diabetes increases year by year.The prevalence of developed country's diabetes is up to 5%～10%, and the prevalence of China has reached 3%.
Type 2 diabetes mellitus also is adult's morbidity type diabetes, how to fall ill after 35～40 years old, accounts for diabetics more than 90%.The ability that produces insulin in the type 2 diabetes mellitus patient body is not to completely lose, insulin even generation are too much in the patient's body that has, but because the insulin resistant effect of body enhancing, and make the action effect of insulin not obvious, so the intravital insulin deficit of patient is a kind of relative shortage.
Compound recipe of the present invention is to be made up of two kinds of hypoglycemic medicines, and two kinds of drug mechanism differences can play complementary effect.Be used for the treatment of diet control and the type 2 diabetes mellitus that still can not suitably control of motion, also can be used for taking separately metformin hydrochloride or the out of contior type 2 diabetes mellitus of vildagliptin.
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.
Vildagliptin (vildagliptin) is a kind of DPP IV (DPP-IV) inhibitor, also claim the incretin reinforcing agent, by suppressing the activity of DPP-IV, reduce the degradation speed of pancreas hyperglycemia sample peptide I GLP-1, and then under hyperglycemia concentration, stimulate secretion of insulin, and can discharge, promote beta Cell of islet propagation and approach such as differentiation and enhancing satietion to bring into play anti-type 2 diabetes mellitus function by delay gastric emptying, glucagon suppression.This product chemistry 1-[[(3-hydroxyl by name-1-adamantyl) amino] acetyl group]-2-cyano group-(S)-tetrahydro pyrrolidine, molecular formula is C
17H
25N
30
2, relative molecular mass is 303.4.Its chemical constitution is as follows:
By retrieval, do not see the pertinent literature and the patent report of relevant compound metformin hydrochloride and vildagliptin.
Summary of the invention
Having the purpose of this invention is to provide a kind of is the Pharmaceutical composition of active component with metformin hydrochloride and vildagliptin, and it is the active component that forms with metformin hydrochloride and vildagliptin, with the Pharmaceutical composition of mixing acceptable accessories formation.
This Pharmaceutical composition can be made into oral formulations.Its oral formulations includes but are not limited to any one solid dosage forms in tablet, capsule, granule, dispersible tablet, chewable tablet, buccal tablet, effervescent tablet, the effervescent granule.In described Pharmaceutical composition, the unit formulation content of its metformin hydrochloride is 125mg～2000mg.Be preferably 500mg～1000mg.The unit formulation content of vildagliptin is 25mg～200mg.Be preferably 50mg～100mg.Draw by analysis, the compound of described metformin hydrochloride and vildagliptin, special preferred compositions is 500mg+50mg in its per unit dosage, 1000mg+50mg, 500mg+100mg, 500mg+100mg.
Pharmaceutical composition of the present invention can be used for the treatment of diet control and the type 2 diabetes mellitus that still can not suitably control of motion, also can be used for taking separately metformin hydrochloride or the out of contior type 2 diabetes mellitus of vildagliptin.
The present invention also provides following pharmacological evaluation, further specifies the suitability of Pharmaceutical composition of the present invention.Experimental technique: the foundation of diabetes rat model: select adult Wistar rats for use, male, body weight 230～260g freely drinks water in the experimentation.Use pH4.5, (concentration is 10mgmL to 0.1mmolL citrate buffer preparation streptozotocin for Streptozotocin, STZ) solution
-1Behind the rat fasting 16h, streptozotocin solution 55mgkg
-1Inferior property lumbar injection.After 7 days, the socket of the eye vein is got blood and is surveyed blood glucose, with fasting glucose 〉=11.11mmolL
-1The person elects diabetic mice as.Selected diabetes rat is divided into 5 groups at random by body weight and blood glucose value.First group is diabetic model group, presses 10mLkg
-1Irritate stomach and give distilled water; Second group is compound metformin group (metformin and vildagliptin proportioning 500: 50), presses 200mgkg
-1Irritate stomach and give compound metformin solution; The 3rd group is the metformin group, presses 200mgkg
-1Irritate stomach and give metformin solution; The 4th group is the vildagliptin group, presses 200mgkg and irritates stomach to vildagliptin solution; And organize in contrast with the normal rat that body weight, Mus are complementary age, irritate stomach by 10mLkg and give ordinary water.Each is organized rat and weighed 1 time in per 3 days, and adjusts the administration volume according to the weight of animals.1 blood glucose of per 4 week mensuration, saccharifying serum albumin (GSP).
2. statistical disposition: statistical data all adopts the mean earthwork, and poor (x ± s) represent, each is organized between the group of data and relatively uses the t inspection statistics.
3 results:
3.1 compound metformin is to the influence (seeing Table 1) of diabetes rat body weight.
Table 1 compound metformin to the influence of diabetes rat body weight (mg) (x ± s, n=15)
By table 1 as seen, after giving the streptozotocin moulding, the diabetes rat body weight significantly is lower than the normal control group, prolongation along with the course of disease, the model group rat body weight presents lasting downward trend (P＜0.01), after giving the compound metformin treatment, the diabetes rat weight recovery is very fast, but still significantly is lower than normal control group (P＜0.01).
3.2 compound metformin is to the influence (seeing Table 2) of blood glucose in diabetic rats.
Table 2 compound metformin is to the influence of blood glucose in diabetic rats (x ± s.n=15)
By table 3 as seen, the normal matched group fasting blood sugar of diabetes rat significantly raises (P＜0.01), and after the compound metformin treatment, the diabetes rat fasting glucose significantly reduces, and blood sugar reducing function is steady, and is lasting.
3.3 compound metformin is to the influence (seeing Table 3) of diabetes rat saccharifying serum albumin (GSP).
Table 3 compound metformin is to the influence of diabetes rat saccharifying serum albumin (GSP) (x ± s)
By table 3 as seen, the normal matched group saccharifying serum albumin of diabetes rat significantly raise (P＜0.01), after the compound metformin treatment, diabetes rat saccharifying serum albumin content obviously reduces (P＜0.01), the prompting compound metformin can be good at the fluctuation of blood sugar control, and can be good at suppressing the nonenzymatic glycosylation reaction of serum albumin.
The specific embodiment
Come metformin hydrochloride of the present invention and vildagliptin preparation done further specifying by following example, but be not limited in following example.
Embodiment 1 metformin hydrochloride and vildagliptin tablet
Prescription:
Preparation method:
Vildagliptin, microcrystalline Cellulose are crossed 80 mesh sieves respectively, and mix homogeneously is adopting the equivalent method of progressively increasing to mix with metformin hydrochloride, fully stirs to make evenly, and is standby; 50% alcoholic solution is joined in the mixed powder, the system soft material, 24 mesh sieves are granulated, drying, 20 mesh sieve granulate add micropowder silica gel, CMS-Na, adopt suitable punch die compressed tablets behind the mix homogeneously, promptly.
If carry out coating for above-mentioned tablet, then obtain coated tablet, can be Film coated tablets, enteric coatel tablets etc.
Embodiment 2: metformin hydrochloride and vildagliptin capsule
Prescription:
Preparation method:
Vildagliptin, metformin hydrochloride are all crossed 80 mesh sieves, progressively increase behind the method mix homogeneously, add magnesium stearate according to equivalent, mix homogeneously, packing, promptly.
Used capsule shells can be conventional capsule, also can be enteric coated capsule.
Embodiment 3: metformin hydrochloride and vildagliptin chewable tablet
Prescription:
Preparation method:
Supplementary materials such as vildagliptin, metformin, xylitol, mannitol are crossed 80 mesh sieves respectively, adopt equivalent incremental method mix homogeneously, add the 2%PVP-k30 alcoholic solution, the system soft material, 16 mesh sieves are granulated, drying, 20 mesh sieve granulate, the correctives, sweeting agent, the fluidizer mix homogeneously that add other, tabletting, promptly.
Embodiment 4: metformin hydrochloride and vildagliptin dispersible tablet
Prescription
Preparation method:
Supplementary materials such as vildagliptin, metformin hydrochloride, microcrystalline Cellulose are crossed 80 mesh sieves respectively, adopt equivalent incremental method mix homogeneously, standby; Add 75% alcoholic solution, the system soft material, 16 mesh sieves are granulated, drying, 20 mesh sieve granulate add other correctives orange flavor, sweeting agent stevioside, fluidizer micropowder silica gel, mix homogeneously such as disintegrating agent PPVP, L-HPC, tabletting, promptly.
Embodiment 5: metformin hydrochloride and vildagliptin effervescent tablet
Prescription
Preparation method:
Metformin hydrochloride and vildagliptin are crossed 80 mesh sieves, mix homogeneously; Get half mixed powder amount, with the citric acid mix homogeneously, with 50% alcoholic solution system soft material, 18 orders are granulated, drying, 16 order granulate; Get the surplus mixed powder again, mix with sodium carbonate, sodium bicarbonate, the same method is granulated; Two kinds of granules of gained mix, and add other adjuvant, and as mix homogeneously such as PEG6000, orange flavor, acesulfame potassium, sodium chloride, tabletting promptly.
Embodiment 5: metformin hydrochloride and vildagliptin granule
Prescription
Preparation method:
Metformin hydrochloride, vildagliptin, mannitol, sorbitol were waited 80 mesh sieves, mix homogeneously; With the 75% alcoholic solution system soft material of 5%PVPk-30,16 orders are granulated, drying, and 12 order granulate add other adjuvant, and as mix homogeneously such as orange flavor, acesulfame potassiums, packing is promptly.
Claims (7)
- The present invention for a kind of be the Pharmaceutical composition of active component with metformin hydrochloride and vildagliptin, it is characterized in that it is the active component that is formed by metformin hydrochloride and vildagliptin, with the Pharmaceutical composition of mixing acceptable accessories formation.
- 2. Pharmaceutical composition as claimed in claim 1 is characterized in that, can be made into oral formulations.
- 3. Pharmaceutical composition as claimed in claim 2 is characterized in that, its oral formulations is any one solid dosage formss such as tablet, capsule, granule, dispersible tablet, chewable tablet, buccal tablet, effervescent tablet, effervescent granule.
- 4. as the described Pharmaceutical composition of claim 1～3, it is characterized in that the unit formulation content of described metformin hydrochloride is 125mg～2000mg.Be preferably 500mg～1000mg.
- 5. as the described Pharmaceutical composition of claim 1～3, it is characterized in that the unit formulation content of described vildagliptin is 25mg～200mg.Be preferably 50mg～100mg.
- 6. as the described Pharmaceutical composition of claim 1～5, it is characterized in that the compound of described metformin hydrochloride and vildagliptin, special preferred compositions is 500mg+50mg in its unit dose, 1000mg+50mg, 500mg+100mg, 500mg+100mg.
- 7. the described Pharmaceutical composition of claim 1～6 can be used for the treatment of the type 2 diabetes mellitus that diet control and motion still can not suitably control, and also can be used for taking separately metformin hydrochloride or the out of contior type 2 diabetes mellitus of vildagliptin.
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| CNA2008100558154A CN101234105A (en) | 2008-01-09 | 2008-01-09 | Pharmaceutical composition containing diabetosan and vildagliptin and preparation thereof |
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| CNA2008100558154A CN101234105A (en) | 2008-01-09 | 2008-01-09 | Pharmaceutical composition containing diabetosan and vildagliptin and preparation thereof |
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