CN101897696A - Sugar-lowering drug composition and application thereof - Google Patents
Sugar-lowering drug composition and application thereof Download PDFInfo
- Publication number
- CN101897696A CN101897696A CN200910086277XA CN200910086277A CN101897696A CN 101897696 A CN101897696 A CN 101897696A CN 200910086277X A CN200910086277X A CN 200910086277XA CN 200910086277 A CN200910086277 A CN 200910086277A CN 101897696 A CN101897696 A CN 101897696A
- Authority
- CN
- China
- Prior art keywords
- vildagliptin
- medicine composition
- hypoglycemic medicine
- vitamin
- folic acid
- 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.)
- Granted
Links
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- 239000000203 mixture Substances 0.000 title claims abstract description 158
- 229940079593 drug Drugs 0.000 title claims abstract description 21
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- 229960001254 vildagliptin Drugs 0.000 claims abstract description 156
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 28
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 208000002249 Diabetes Complications Diseases 0.000 claims abstract description 14
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- 235000019156 vitamin B Nutrition 0.000 claims abstract description 13
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- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 285
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- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 claims description 143
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Abstract
The invention relates to a sugar-lowering drug composition and application thereof. The composition comprises 1) medicinal dosage of vildagliptin, 2) medicinal dosage of any one or combination of thiazolidinedione sugar-lowering drugs or medicinal salt thereof, sulfonylurea sugar-lowering drugs or medicinal salt thereof or biguanide sugar-lowering drugs or medicinal salt thereof and 3) B vitamins. The invention relates to application of the sugar-lowering drug composition to preparing the drugs for treating and/or controlling diabetes or diabetic complications. The composition can effectively overcome the defect that type 2 diabetes can not be controlled by singly taking the commonly used sugar-lowering drugs or vildagliptin in the prior art and simultaneously addition of the B vitamins is conductive to enhancing the treatment effect of the drug, effectively controlling the blood sugar, protecting the endothelial cell functions in a synergic manner, slowing rising of plasma homocysteine of the diabetes patients, especially the diabetes patients associated with chronic complications and reducing the diabetic complications.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition, particularly relating to a kind of is hypoglycemic medicine composition of main active and uses thereof with vildagliptin, other hypoglycemic medicines and vitamin B group.
Background technology
Diabetes (Diabetes Inellitus) are a kind of metabolic diseases of multi-pathogenesis, are characterized in chronic hyperglycemia, follow because of insulin secretion and/or effect the defective sugar, fat and the protein metabolism disorder that cause.Diabetes can betide any age, along with the course of disease prolongs, the infringement of histopathologies such as easy concurrent whole body nerve, blood capillary and macroangiopathy, and can cause histoorgans such as the heart, brain, kidney, nerve and eye chronic, carry out sexually transmitted disease (STD) and become, so that final take place blind, lower limb are gangrenous, uremia, apoplexy or myocardial infarction, even threat to life.Along with growth in the living standard, diabetes have become a kind of commonly encountered diseases, and its sickness rate is also increasing year by year.At present, the prevalence of developed country's diabetes is up to 5%-10%, and also oneself reaches 3% to the prevalence of China.It in the diabetic type 2 diabetes mellitus, 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 strengthens, and make the action effect of insulin not obvious, so the intravital insulin deficit of patient is a kind of relative shortage.Patient at type 2 diabetes mellitus their early stage 70%～85% needs oral hypoglycemic drug therapy, and clinical oral antidiabetic thing commonly used comprises sulfonylurea, biguanides, thiazolidinediones (glitazone) etc. at present, and these medicines have following shortcoming:
Sulphanylureas mainly is by closing adenosine triphosphate sensitive potassium (K on the beta Cell of islet film
ATP) passage increases endogenous insulin secretion.Shortcoming is: for 1 type that does not have the insulin secretion ability, type 2 diabetes mellitus patient, this medicine does not almost have effect; Side effect such as the hypoglycemia of initiation, weight increase, skin allergy, digestive tract reaction are arranged simultaneously.
Thiazolidinediones is the part of nucleus peroxisome multiplicaiton factor activated receptor (PPAR-γ), can increase the ability that peripheral tissues removes glucose, reduce glycogen output, the glycogen picked-up when increasing glucose load, thereby effectively blood sugar lowering improves insulin sensitivity.Shortcoming is: be only applicable to the type 2 diabetes mellitus patient that pancreas has certain insulin secretion ability; Can cause liver dysfunction and edema, increase the patients with heart failure water-sodium retention, thereby increase the weight of the heart burden.
The biguanides blood sugar reducing function mainly is to promote the fatty tissue ingestion of glucose, and muscular tissue anerobic glycolysis is increased, and increases the utilization of glucose, and inhibition or delay glucose there is no hypoglycemic activity in gastrointestinal absorption to the normal person.Biguanide antidiabetic medicament is unsuitable for the lighter patient of body weight and takes, and its topmost side effect is to cause lactic acidosis.
Vildagliptin (vildagliptin) is a kind of DPP IV (DPP-IV) inhibitor, also claim the incretin reinforcing agent, this medicine is 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.Vildagliptin does not have obvious influence to body weight, and its side effect only limits to hypoglycemia and edema, and is very nearly the same with the effectiveness of placebo, takes the situation that vildagliptin can not be controlled type 2 diabetes mellitus separately but exist yet.
Vitamin B group comprises folic acid, vitamin B12 (cobalamin), vitamin B6 (pyridoxol), all is the indispensable micronutrient of health.For the research of vitamin B group, what receive much attention at present is folic acid, vitamin B12 and vitamin B6.
Summary of the invention
The purpose of this invention is to provide a kind of hypoglycemic medicine composition and uses thereof; effectively solve prior art and take the defective that hypoglycemic medicine commonly used or vildagliptin can not be controlled type 2 diabetes mellitus separately, add vitamin B group simultaneously and have effective blood sugar control, coordinating protection inner skin cell function, reduce effect such as diabetic complication.
For achieving the above object, the invention provides a kind of hypoglycemic medicine composition, comprising:
1) vildagliptin of pharmaceutical dosage;
2) biguanides of the sulphanylureas of the thiazolidinediones of pharmaceutical dosage or its officinal salt, pharmaceutical dosage or its officinal salt or pharmaceutical dosage or any one or combination in any in its officinal salt;
3) vitamin B group.
Described hypoglycemic medicine composition also comprises pharmaceutically suitable carrier or excipient.
On the basis of technique scheme, described hypoglycemic medicine composition also comprises the vitamin B group of pharmaceutical dosage.Described vitamin B group is specially any one or the combination in any in folic acid, vitamin B12 or the vitamin B6.The pharmaceutical dosage of described folic acid is 0.1-7.5mg; The pharmaceutical dosage of described vitamin B12 is 0.005-2mg; The pharmaceutical dosage of described vitamin B6 is 2-75mg.
The pharmaceutical dosage of described vildagliptin is 25-200mg.Further, the pharmaceutical dosage of described vildagliptin is 50-100mg.
In technique scheme, described thiazolidinediones antidiabetic drug or its officinal salt are any one or the combination in any in rosiglitazone, rosiglitazone maleate, pioglitazone, pioglitazone hydrochloride, troglitazone, englitazone or the ciglitazone.Further, described thiazolidinediones antidiabetic drug is specially at least a in rosiglitazone and the pioglitazone.The pharmaceutical dosage of described rosiglitazone is 1-8mg; The pharmaceutical dosage of described pioglitazone is 7.5-45mg.
In technique scheme, described sulfonylureas drugs for diabetes is any one or the combination in any in glibenclamide, glibornuride, glycyclamide, glyhexamide, glimepiride, glypinamide, glisamuride, Glisentide, glisolamide, glyoctamide, gliclazide, glipizide or the gliquidone.Further, described sulfonylureas drugs for diabetes is specially any one or the combination in any in glibenclamide, glimepiride, gliclazide, glipizide or the gliquidone.The pharmaceutical dosage of described glibenclamide is 1-15mg; The pharmaceutical dosage of described glimepiride is 1-4mg; The pharmaceutical dosage of described gliclazide is 20-160mg; The pharmaceutical dosage of described glipizide is 1-15mg; The pharmaceutical dosage of described gliquidone is 15-60mg.
In technique scheme, described biguanides antidiabetic drug is any one or the combination in any in metformin, phenformin or the buformin.Further, described biguanides antidiabetic drug is specially metformin.The pharmaceutical dosage of described metformin is 125-2000mg.Preferably, the pharmaceutical dosage of described metformin is 500-1000mg.
For achieving the above object, the present invention also provides a kind of pharmacy dosage form that comprises described hypoglycemic medicine composition, comprise conventional tablet, bilayer tablet, multilayer tablet, slow releasing tablet, single chamber controlled release tablet, two chambers controlled release tablet, pore type controlled release tablet, sublingual lozenge, oral cavity quick disintegrating slice, dispersible tablet, enteric coatel tablets, granule, pill, enteric coated capsule, delayed-release tablet, regularly/position releasing piece, conventional capsule, slow releasing capsule, controlled release capsule, contain micropill or small pieces capsule, contain pH dependent form capsule, oral liquid, membrane or the patch of micropill or small pieces.
For achieving the above object, the present invention also provides a kind of described hypoglycemic medicine composition to treat and/or prevent purposes in diabetes or the diabetes complicated disease drug in preparation.Wherein, diabetic complication comprises chronic complicating diseases and acute complications, refers to chronic complicating diseases especially; Described chronic complicating diseases comprises diabetes cardiovascular complication, diabetic nephropathy, diabetic neuropathy, diabetic renal papillary necrosis, diabetic foot, diabetic dermopathy etc.
The invention provides a kind of hypoglycemic medicine composition and uses thereof, this hypoglycemic medicine composition comprises (1) vildagliptin; (2) any one in thiazolidinediones antidiabetic drug or its officinal salt, sulfonylureas drugs for diabetes or its officinal salt or biguanides antidiabetic drug or its officinal salt or combination in any, 3) vitamin B group.This hypoglycemic medicine composition is blood sugar control effectively; the coordinating protection inner skin cell function; alleviate diabetics and particularly be associated with the diabetics homocysteine in plasma rising of chronic complicating diseases, and can reduce the generation of diabetic complication, have synergy.Pharmaceutical composition provided by the invention is on the effective therapeutic effect of diabetes, beneficial effect with tangible prevent diabetes complication, therefore be antidiabetic medicine preferably, provide a kind of feasible, safe therapeutic scheme for treating and/or preventing diabetes or diabetic complication.
Below by embodiment, technical scheme of the present invention is described in further detail.
The specific embodiment
In the present invention, the pharmaceutical dosage of folic acid is 0.1-7.5mg, and the pharmaceutical dosage of vitamin B12 is 0.005-2mg, and the pharmaceutical dosage of vitamin B6 is 2-75mg.
A kind of hypoglycemic medicine composition first embodiment of the present invention
Hypoglycemic medicine composition comprises 25mg vildagliptin, 2000mg metformin and 0.1mg folic acid.
Compound metformin and vildagliptin folic acid tablet (1000 amounts) preparation method:
Prescription: metformin 400g
Vildagliptin 5g
Folic acid 800mg
Starch 100g
Microcrystalline Cellulose 100g
Carboxymethyl starch sodium 75g
Low-substituted hydroxypropyl cellulose 75g
The polyvidone alcoholic solution is an amount of
Magnesium stearate 0.5%
Preparation method: the adjuvant in the above-mentioned prescription was pulverized 80 mesh sieves, drying for standby.Get the 400g metformin, the 5g vildagliptin, 800mg folic acid is according to equivalent incremental method mix homogeneously, add starch respectively according to formula ratio, microcrystalline Cellulose, carboxymethyl starch sodium and low-substituted hydroxypropyl cellulose, by equivalent incremental method uniform mixing, make soft material with 5% 30 POVIDONE K 30 BP/USP 29/30-95% alcoholic solution, 20 mesh sieves are granulated, 40 ℃ of following dry 2h of temperature, 18 mesh sieve granulate, making particulate water content is 2-3%, dried granule and magnesium stearate mix homogeneously are made semi-finished product, semi-finished product are detected, measure content, be pressed into tablet (1000) with tablet machine.The tablet of making need be used aluminium-plastic bubble plate packing, keeps in Dark Place.
During use according to five parts of tablets.
In the present embodiment, metformin can also be any one or the combination in any between four in metformin hydrochloride, phenformin or the buformin; Folic acid can also be any one or the triangular combination in any in vitamin B12 or the vitamin B6.
A kind of hypoglycemic medicine composition second embodiment of the present invention
Hypoglycemic medicine composition comprises 50mg vildagliptin, 1000mg metformin and 0.4mg folic acid.
In the present embodiment among compound metformin and vildagliptin folic acid tablet (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 17 embodiment of the present invention compound metformin identical with vildagliptin folic acid tablet (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, metformin can also be any one or the combination in any between four in metformin hydrochloride, phenformin or the buformin; Folic acid can also be any one or the triangular combination in any in vitamin B12 or the vitamin B6.
A kind of hypoglycemic medicine composition the 3rd embodiment of the present invention
Hypoglycemic medicine composition comprises 100mg vildagliptin, 500mg metformin and 7.5mg folic acid.
In the present embodiment among compound metformin and vildagliptin folic acid tablet (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 17 embodiment of the present invention compound metformin identical with vildagliptin folic acid tablet (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, metformin can also be any one or the combination in any between four in metformin hydrochloride, phenformin or the buformin; Folic acid can also be any one or the triangular combination in any in vitamin B12 or the vitamin B6.
A kind of hypoglycemic medicine composition the 4th embodiment of the present invention
Hypoglycemic medicine composition comprises 200mg vildagliptin, 125mg metformin and 2mg vitamin B12.
In the present embodiment among compound metformin and vildagliptin vitamin B12 tablet (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 17 embodiment of the present invention compound metformin identical with vildagliptin folic acid tablet (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, metformin can also be any one or the combination in any between four in metformin hydrochloride, phenformin or the buformin; Vitamin B12 can also be any one or the triangular combination in any in folic acid or the vitamin B6.
A kind of hypoglycemic medicine composition the 5th embodiment of the present invention
Hypoglycemic medicine composition comprises 50mg vildagliptin, 500mg metformin and 10mg vitamin B6.
In the present embodiment among compound metformin and vildagliptin vitamin B6 tablet (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 17 embodiment of the present invention compound metformin identical with vildagliptin folic acid tablet (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, metformin can also be any one or the combination in any between four in metformin hydrochloride, phenformin or the buformin; Vitamin B6 can also be any one or the triangular combination in any in vitamin B12 or the folic acid.
A kind of hypoglycemic medicine composition the 6th embodiment of the present invention
Hypoglycemic medicine composition comprises 25mg vildagliptin, 8mg rosiglitazone and 0.4mg folic acid.
In the present embodiment among compound recipe rosiglitazone and vildagliptin folic acid tablet (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 17 embodiment of the present invention compound metformin identical with vildagliptin folic acid tablet (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 8mg rosiglitazone can also be the 7.5-45mg pioglitazone, or rosiglitazone and the combination of pyrroles's row ketone; Folic acid can also be any one or the triangular combination in any in vitamin B12 or the vitamin B6.
A kind of hypoglycemic medicine composition the 7th embodiment of the present invention
Hypoglycemic medicine composition comprises 50mg vildagliptin, 4mg rosiglitazone and 2mg vitamin B12.
In the present embodiment among compound recipe rosiglitazone and vildagliptin vitamin B12 tablet (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 17 embodiment of the present invention compound metformin identical with vildagliptin folic acid tablet (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 4mg rosiglitazone can also be the 7.5-45mg pioglitazone, or rosiglitazone and the combination of pyrroles's row ketone; Vitamin B12 can also be any one or the triangular combination in any in folic acid or the vitamin B6.
A kind of hypoglycemic medicine composition the 8th embodiment of the present invention
Hypoglycemic medicine composition comprises 100mg vildagliptin, 1mg rosiglitazone and 10mg vitamin B6.
In the present embodiment among compound recipe rosiglitazone and vildagliptin vitamin B6 tablet (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 17 embodiment of the present invention compound metformin identical with vildagliptin folic acid tablet (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 1mg rosiglitazone can also be the 7.5-45mg pioglitazone, or rosiglitazone and the combination of pyrroles's row ketone; Vitamin B6 can also be any one or the triangular combination in any in vitamin B12 or the folic acid.
A kind of hypoglycemic medicine composition the 9th embodiment of the present invention
Hypoglycemic medicine composition comprises 50mg vildagliptin, 7.5mg pioglitazone and 0.4mg folic acid.
In the present embodiment among compound recipe pioglitazone and vildagliptin folic acid tablet (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 17 embodiment of the present invention compound metformin identical with vildagliptin folic acid tablet (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 7.5mg pioglitazone can also be the 1-8mg rosiglitazone, or rosiglitazone and the combination of pyrroles's row ketone; Folic acid can also be any one or the triangular combination in any in vitamin B12 or the vitamin B6.
A kind of hypoglycemic medicine composition the tenth embodiment of the present invention
Hypoglycemic medicine composition comprises 100mg vildagliptin, 15mg pioglitazone and 10mg vitamin B6.
In the present embodiment among compound recipe pioglitazone and vildagliptin vitamin B6 tablet (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 17 embodiment of the present invention compound metformin identical with vildagliptin folic acid tablet (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 15mg pioglitazone can also be the 1-8mg rosiglitazone, or rosiglitazone and the combination of pyrroles's row ketone; Vitamin B6 can also be any one or the triangular combination in any in vitamin B12 or the folic acid.
A kind of hypoglycemic medicine composition the 11 embodiment of the present invention
Hypoglycemic medicine composition comprises 200mg vildagliptin, 45mg pioglitazone and 2mg vitamin B12.
In the present embodiment among compound recipe pioglitazone and vildagliptin vitamin B12 tablet (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 17 embodiment of the present invention compound metformin identical with vildagliptin folic acid tablet (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 45mg pioglitazone can also be the 1-8mg rosiglitazone, or rosiglitazone and the combination of pyrroles's row ketone; Vitamin B12 can also be any one or the triangular combination in any in folic acid or the vitamin B6.
A kind of hypoglycemic medicine composition the 12 embodiment of the present invention
Hypoglycemic medicine composition comprises 25mg vildagliptin, 2.5mg glibenclamide and 0.1mg folic acid.
In the present embodiment among compound recipe glibenclamide and vildagliptin folic acid tablet (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 17 embodiment of the present invention compound metformin identical with vildagliptin folic acid tablet (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 2.5mg glibenclamide can also be any one or the combination in any between five in 1-4mg glimepiride, 20-160mg gliclazide, 1-15mg glipizide or the 15-60mg gliquidone; Folic acid can also be any one or the triangular combination in any in vitamin B12 or the vitamin B6.
A kind of hypoglycemic medicine composition the 13 embodiment of the present invention
Hypoglycemic medicine composition comprises 50mg vildagliptin, 4mg glimepiride and 0.4mg folic acid.
In the present embodiment among compound recipe glimepiride and vildagliptin folic acid tablet (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 17 embodiment of the present invention compound metformin identical with vildagliptin folic acid tablet (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 4mg glimepiride can also be any one or the combination in any between five in 1-15mg glibenclamide, 20-160mg gliclazide, 1-15mg glipizide or the 15-60mg gliquidone; Folic acid can also be any one or the triangular combination in any in vitamin B12 or the vitamin B6.
A kind of hypoglycemic medicine composition the 14 embodiment of the present invention
Hypoglycemic medicine composition comprises 75mg vildagliptin, 50mg gliclazide and 7.5mg folic acid.
In the present embodiment among compound recipe gliclazide and vildagliptin folic acid tablet (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 17 embodiment of the present invention compound metformin identical with vildagliptin folic acid tablet (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 50mg gliclazide can also be any one or the combination in any between five in 1-15mg glibenclamide, 1-4mg glimepiride, 1-15mg glipizide or the 15-60mg gliquidone; Folic acid can also be any one or the triangular combination in any in vitamin B12 or the vitamin B6.
A kind of hypoglycemic medicine composition the 15 embodiment of the present invention
Hypoglycemic medicine composition comprises 100mg vildagliptin, 5mg glipizide and 10mg vitamin B6.
In the present embodiment among compound recipe glipizide and vildagliptin vitamin B6 tablet (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 17 embodiment of the present invention compound metformin identical with vildagliptin folic acid tablet (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 5mg glipizide can also be any one or the combination in any between five in 1-15mg glibenclamide, 1-4mg glimepiride, 20-160mg gliclazide or the 15-60mg gliquidone; Vitamin B6 can also be any one or the triangular combination in any in vitamin B12 or the folic acid.
A kind of hypoglycemic medicine composition the 16 embodiment of the present invention
Hypoglycemic medicine composition comprises 200mg vildagliptin, 30mg gliquidone and 2mg vitamin B12.
In the present embodiment among compound recipe gliquidone and vildagliptin vitamin B12 tablet (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 17 embodiment of the present invention compound metformin identical with vildagliptin folic acid tablet (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 30mg gliquidone can also be any one or the combination in any between five in 1-15mg glibenclamide, 1-4mg glimepiride, 20-160mg gliclazide or the 1-15mg glipizide; Vitamin B12 can also be any one or the triangular combination in any in folic acid or the vitamin B6.
A kind of hypoglycemic medicine composition the 17 embodiment of the present invention
Hypoglycemic medicine composition comprises 25mg vildagliptin, 2000mg metformin and 0.1mg folic acid.
Compound metformin and vildagliptin folic acid capsule (1000 amounts) preparation method:
Prescription: metformin 400g
Vildagliptin 5g
Folic acid 800mg
Microcrystalline Cellulose 5g
Carboxymethyl starch sodium 2.5g
Low-substituted hydroxypropyl cellulose 2.5g
The polyvidone alcoholic solution is an amount of
Micropowder silica gel 1%
Magnesium stearate 1%
Preparation method: the adjuvant in the above-mentioned prescription was pulverized 80 mesh sieves, drying for standby.Get 5g vildagliptin, 800mg folic acid, microcrystalline Cellulose, carboxymethyl starch sodium and low-substituted hydroxypropyl cellulose according to equivalent incremental method mix homogeneously, make soft material with 5% polyvidone alcoholic solution, 30 mesh sieves are granulated, 18 mesh sieve granulate, and making particulate water content is 2-3%; With granule and the 400g first biguanide mix homogeneously that makes, add micropowder silica gel and the abundant mix homogeneously of magnesium stearate, measure content, the Capsules of packing into promptly gets (1000).The capsule of making need be used aluminium-plastic bubble plate packing, keeps in Dark Place.
Take according to five deals during use.
In the present embodiment, metformin can also be any one or the combination in any between four in metformin hydrochloride, phenformin or the buformin; Folic acid can also be any one or the triangular combination in any in vitamin B12 or the vitamin B6.
A kind of hypoglycemic medicine composition the 18 embodiment of the present invention
Hypoglycemic medicine composition comprises 50mg vildagliptin, 1000mg metformin and 0.4mg folic acid.
In the present embodiment among compound metformin and vildagliptin folic acid capsule (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 49 embodiment of the present invention compound metformin identical with vildagliptin folic acid capsule (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, metformin can also be any one or the combination in any between four in metformin hydrochloride, phenformin or the buformin; Folic acid can also be any one or the triangular combination in any in vitamin B12 or the vitamin B6.
A kind of hypoglycemic medicine composition the 19 embodiment of the present invention
Hypoglycemic medicine composition comprises 100mg vildagliptin, 500mg metformin and 7.5mg folic acid.
In the present embodiment among compound metformin and vildagliptin folic acid capsule (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 49 embodiment of the present invention compound metformin identical with vildagliptin folic acid capsule (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, metformin can also be any one or the combination in any between four in metformin hydrochloride, phenformin or the buformin; Folic acid can also be any one or the triangular combination in any in vitamin B12 or the vitamin B6.
A kind of hypoglycemic medicine composition the 20 embodiment of the present invention
Hypoglycemic medicine composition comprises 200mg vildagliptin, 125mg metformin and 2mg vitamin B12.
In the present embodiment among compound metformin and vildagliptin vitamin B12 capsule (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 49 embodiment of the present invention compound metformin identical with vildagliptin folic acid capsule (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, metformin can also be any one or the combination in any between four in metformin hydrochloride, phenformin or the buformin; Vitamin B12 can also be any one or the triangular combination in any in folic acid or the vitamin B6.
A kind of hypoglycemic medicine composition the 21 embodiment of the present invention
Hypoglycemic medicine composition comprises 50mg vildagliptin, 500mg metformin and 10mg vitamin B6.
In the present embodiment among compound metformin and vildagliptin vitamin B6 capsule (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 33 embodiment of the present invention compound metformin identical with vildagliptin folic acid capsule (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, metformin can also be any one or the combination in any between four in metformin hydrochloride, phenformin or the buformin; Vitamin B6 can also be any one or the triangular combination in any in vitamin B12 or the folic acid.
A kind of hypoglycemic medicine composition the 22 embodiment of the present invention
Hypoglycemic medicine composition comprises 25mg vildagliptin, 8mg rosiglitazone and 0.4mg folic acid.
In the present embodiment among compound recipe rosiglitazone and vildagliptin folic acid capsule (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 49 embodiment of the present invention compound metformin identical with vildagliptin folic acid capsule (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 8mg rosiglitazone can also be the 7.5-45mg pioglitazone, or rosiglitazone and the combination of pyrroles's row ketone; Folic acid can also be any one or the triangular combination in any in vitamin B12 or the vitamin B6.
A kind of hypoglycemic medicine composition the 23 embodiment of the present invention
Hypoglycemic medicine composition comprises 50mg vildagliptin, 4mg rosiglitazone and 2mg vitamin B12.
In the present embodiment among compound recipe rosiglitazone and vildagliptin vitamin B12 capsule (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 49 embodiment of the present invention compound metformin identical with vildagliptin folic acid capsule (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 4mg rosiglitazone can also be the 7.5-45mg pioglitazone, or rosiglitazone and the combination of pyrroles's row ketone; Vitamin B12 can also be any one or the triangular combination in any in folic acid or the vitamin B6.
A kind of hypoglycemic medicine composition the 24 embodiment of the present invention
Hypoglycemic medicine composition comprises 100mg vildagliptin, 1mg rosiglitazone and 10mg vitamin B6.
In the present embodiment among compound recipe rosiglitazone and vildagliptin vitamin B6 capsule (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 49 embodiment of the present invention compound metformin identical with vildagliptin folic acid capsule (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 1mg rosiglitazone can also be the 7.5-45mg pioglitazone, or rosiglitazone and the combination of pyrroles's row ketone; Vitamin B6 can also be any one or the triangular combination in any in vitamin B12 or the folic acid.
A kind of hypoglycemic medicine composition the 25 embodiment of the present invention
Hypoglycemic medicine composition comprises 50mg vildagliptin, 7.5mg pioglitazone and 0.4mg folic acid.
In the present embodiment among compound recipe pioglitazone and vildagliptin folic acid capsule (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 49 embodiment of the present invention compound metformin identical with vildagliptin folic acid capsule (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 7.5mg pioglitazone can also be the 1-8mg rosiglitazone, or rosiglitazone and the combination of pyrroles's row ketone; Folic acid can also be any one or the triangular combination in any in vitamin B12 or the vitamin B6.
A kind of hypoglycemic medicine composition the 26 embodiment of the present invention
Hypoglycemic medicine composition comprises 100mg vildagliptin, 15mg pioglitazone and 10mg vitamin B6.
In the present embodiment among compound recipe pioglitazone and vildagliptin vitamin B6 capsule (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 49 embodiment of the present invention compound metformin identical with vildagliptin folic acid capsule (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 15mg pioglitazone can also be the 1-8mg rosiglitazone, or rosiglitazone and the combination of pyrroles's row ketone; Vitamin B6 can also be any one or the triangular combination in any in vitamin B12 or the folic acid.
A kind of hypoglycemic medicine composition the 27 embodiment of the present invention
Hypoglycemic medicine composition comprises 200mg vildagliptin, 45mg pioglitazone and 2mg vitamin B12.
In the present embodiment among compound recipe pioglitazone and vildagliptin vitamin B12 capsule (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 49 embodiment of the present invention compound metformin identical with vildagliptin folic acid capsule (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 45mg pioglitazone can also be the 1-8mg rosiglitazone, or rosiglitazone and the combination of pyrroles's row ketone; Vitamin B12 can also be any one or the triangular combination in any in folic acid or the vitamin B6.
A kind of hypoglycemic medicine composition the 28 embodiment of the present invention
Hypoglycemic medicine composition comprises 25mg vildagliptin, 2.5mg glibenclamide and 0.1mg folic acid.
In the present embodiment among compound recipe glibenclamide and vildagliptin folic acid capsule (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 49 embodiment of the present invention compound metformin identical with vildagliptin folic acid capsule (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 2.5mg glibenclamide can also be any one or the combination in any between five in 1-4mg glimepiride, 20-160mg gliclazide, 1-15mg glipizide or the 15-60mg gliquidone; Folic acid can also be any one or the triangular combination in any in vitamin B12 or the vitamin B6.
A kind of hypoglycemic medicine composition the 29 embodiment of the present invention
Hypoglycemic medicine composition comprises 50mg vildagliptin, 4mg glimepiride and 0.4mg folic acid.
In the present embodiment among compound recipe glimepiride and vildagliptin folic acid capsule (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 49 embodiment of the present invention compound metformin identical with vildagliptin folic acid capsule (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 4mg glimepiride can also be any one or the combination in any between five in 1-15mg glibenclamide, 20-160mg gliclazide, 1-15mg glipizide or the 15-60mg gliquidone; Folic acid can also be any one or the triangular combination in any in vitamin B12 or the vitamin B6.
A kind of hypoglycemic medicine composition the 30 embodiment of the present invention
Hypoglycemic medicine composition comprises 75mg vildagliptin, 50mg gliclazide and 7.5mg folic acid.
In the present embodiment among compound recipe gliclazide and vildagliptin folic acid capsule (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 49 embodiment of the present invention compound metformin identical with vildagliptin folic acid capsule (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 50mg gliclazide can also be any one or the combination in any between five in 1-15mg glibenclamide, 1-4mg glimepiride, 1-15mg glipizide or the 15-60mg gliquidone; Folic acid can also be any one or the triangular combination in any in vitamin B12 or the vitamin B6.
A kind of hypoglycemic medicine composition of the present invention hentriaconta-embodiment
Hypoglycemic medicine composition comprises 100mg vildagliptin, 5mg glipizide and 10mg vitamin B6.
In the present embodiment among compound recipe glipizide and vildagliptin vitamin B6 capsule (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 49 embodiment of the present invention compound metformin identical with vildagliptin folic acid capsule (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 5mg glipizide can also be any one or the combination in any between five in 1-15mg glibenclamide, 1-4mg glimepiride, 20-160mg gliclazide or the 15-60mg gliquidone; Vitamin B6 can also be any one or the triangular combination in any in vitamin B12 or the folic acid.
A kind of hypoglycemic medicine composition the 32 embodiment of the present invention
Hypoglycemic medicine composition comprises 200mg vildagliptin, 30mg gliquidone and 2mg vitamin B12.
In the present embodiment among compound recipe gliquidone and vildagliptin vitamin B12 capsule (1000 amounts) preparation method and a kind of hypoglycemic medicine composition the 49 embodiment of the present invention compound metformin identical with vildagliptin folic acid capsule (1000 amounts) preparation method, can select the selection of carrier or excipient or adjust carrier or the dosage of excipient for the common technology means that realize this pharmaceutical composition of preparation according to this area.
In the present embodiment, the 30mg gliquidone can also be any one or the combination in any between five in 1-15mg glibenclamide, 1-4mg glimepiride, 20-160mg gliclazide or the 1-15mg glipizide; Vitamin B12 can also be any one or the triangular combination in any in folic acid or the vitamin B6.
Further specify the prevention and the therapeutic effect of hypoglycemic medicine composition of the present invention below by concrete pharmacological evaluation.
Test the influence of 1 vildagliptin, metformin and folate composition to blood glucose in diabetic rats, inner skin cell function and nephropathy
Purpose: observe the influence of vildagliptin, metformin and folate composition to diabetes (type 2 diabetes mellitus) rat blood sugar, blood plasma NO and urine protein.
Experiment material:
1. reagent: streptozotocin (STZ), citric acid, sodium hydroxide, glucose, thiamazole.
2. laboratory animal: the Wistar rat, male, body weight 200-250g.
3. instrument: semi-automatic biochemical analyzer
4, experimental technique:
The preparation of high heat feedstuff (composition of every 5kg): cholesterol 50g, Adeps Sus domestica 250g, Oleum Arachidis hypogaeae semen 250g, yolk powder 250g, thiamazole 1g, sucrose 100g, normal diet 4.1kg, other gets 500g starch and is washed into pasty state with boiling water, mixing.
The type 2 diabetes mellitus Preparation of model: 8 Wistar rats of picked at random are as normal control, and all the other rat tail vein injection STZ (30mg/kg) are aided with normal feedstuff and feed.
Method and approach
The rat that filters out impaired glucose tolerance is divided into 8 groups, be respectively model control group, vildagliptin group (5mg/kg), metformin group (50mg/kg), folic acid group (0.08mg/kg), vildagliptin+metformin group (5mg/kg+50mg/kg), vildagliptin+folic acid group (5mg/kg+0.08mg/kg), metformin+folic acid group (50mg/kg+0.08mg/kg), vildagliptin+metformin+folic acid group (5mg/kg+50mg/kg+0.08mg/kg) and normal control group, 8 every group.Each is organized and all gives relative medicine 1 time by 1ml/100g administration volume filling stomach every day, and normal control group and model control group give the equal-volume normal saline.Except that the normal control group was fed normal diet, all the other each groups were all fed with the high heat feedstuff simultaneously.Experimental session animal drinking-water and feedstuff do not add restriction.Successive administration is after 10 weeks, and tail vein blood is surveyed blood glucose and NO content; The metabolic cage method accesses the 24h urine, measures the 24h urine albumen amount.
5, statistical method: data mean ± standard deviation
Expression, the t that relatively goes between group checks.
6, experimental result
(1) vildagliptin, metformin and folate composition are to the influence of blood glucose
Experimental result is as shown in table 1, and model group blood glucose significantly raises, and vildagliptin, metformin list are used all significantly blood sugar lowering, and the folic acid list is used does not have obvious effect to blood glucose; Vildagliptin and metformin share significantly blood sugar lowering, share to be better than arbitrary medicine list usefulness; Vildagliptin, metformin and folate composition have remarkable blood sugar reducing function, are better than arbitrary single medicine, but not remarkable to the advantageous effect of vildagliptin and metformin compound recipe.Above-mentioned experimental result explanation vildagliptin, metformin and folate composition be blood sugar control better.
Table 1 vildagliptin, metformin and folate composition are to the influence of type 2 diabetes mellitus rat blood sugar
Annotate: * P＜0.05, compare with model control group * * P＜0.01; Compare with vildagliptin with single #P＜0.05; Compare with metformin with single $P＜0.05; ﹠amp; Compare with the folic acid group P＜0.05.
(2) vildagliptin, metformin and folate composition are to the influence of 24h urine protein and blood plasma NO
Experimental result is as shown in table 2, and the model group urine protein significantly raises, and single medicine group all has a declining tendency, but all not remarkable; Vildagliptin+folic acid group, metformin+folic acid group can significantly reduce urine protein, this shows, folic acid has certain effect at tool aspect the protection kidney; Metformin+vildagliptin group also can significantly reduce urine protein; and vildagliptin, metformin and folate composition effect are the most obvious; significantly be better than model group, vildagliptin+folic acid group, metformin+folic acid group and metformin+vildagliptin group, the effect that has collaborative renal function protecting between three medicines is described.
Model group blood plasma NO significantly reduces, and single medicine group all has trend of rising, but all not remarkable; Vildagliptin+folic acid group, metformin+folic acid group be elevation of NO significantly; this shows; folic acid has protective effect aspect the protection endotheliocyte; metformin+vildagliptin group is remarkable elevation of NO also; and vildagliptin, metformin and folate composition effect are the most obvious; significantly be better than model group, vildagliptin+folic acid group, metformin+folic acid group and metformin+vildagliptin group, the effect that also has collaborative protection endotheliocyte between three medicines is described.
Table 2 vildagliptin, metformin and folate composition are to the influence of 24h urine protein and blood plasma NO
Annotate: * P＜0.05, compare with model control group * * P＜0.01; Compare with vildagliptin+folic acid group #P＜0.05; Compare with metformin+folic acid group $P＜0.05; ﹠amp; Compare with metformin+vildagliptin group P＜0.05.
Test 2 vildagliptins, rosiglitazone, folic acid and add of the influence of VB12 compositions blood glucose in diabetic rats, inner skin cell function and nephropathy
Purpose: observation vildagliptin, rosiglitazone, folic acid add the influence of VB12 compositions to diabetes (type 2 diabetes mellitus) rat blood sugar, blood plasma NO and urine protein.
Experiment material:
1, reagent, laboratory animal, instrument are all with experiment 1.
2, experimental technique:
(1) preparation of high heat feedstuff (composition of every 5kg), type 2 diabetes mellitus Preparation of model are all with experiment 1.
(2) method and approach
The rat that filters out impaired glucose tolerance is divided into 8 groups, be respectively model control group, vildagliptin group (5mg/kg), rosiglitazone group (1.5mg/kg), folic acid VB12 group (0.08+0.2mg/kg), vildagliptin+rosiglitazone group (5mg/kg+1.5mg/kg), rosiglitazone+folic acid VB12 group (1.5mg/kg+0.08mg/kg+0.2mg/kg), vildagliptin+folic acid VB12 group (5mg/kg+0.08mg/kg+0.2mg/kg), vildagliptin+rosiglitazone+folic acid VB12 organizes (5mg/kg+1.5mg/kg+0.08mg/kg+0.2mg/kg) and normal control group, 8 every group.Each is organized and all gives relative medicine 1 time by 1ml/100g administration volume filling stomach every day, and normal control group and model control group give the equal-volume normal saline.Except that the normal control group was fed normal diet, all the other each groups were all fed with the high heat feedstuff simultaneously.Experimental session animal drinking-water and feedstuff do not add restriction.Successive administration is after 10 weeks, and tail vein blood is surveyed blood glucose and NO content; The metabolic cage method accesses the 24h urine, measures the 24h urine albumen amount.
5, statistical method: data mean ± standard deviation
Expression, the t that relatively goes between group checks.
6, experimental result
(1) vildagliptin, rosiglitazone, folic acid VB12 compositions are to the influence of blood glucose
Table 3 vildagliptin, rosiglitazone, folic acid VB12 compositions are to the influence of type 2 diabetes mellitus rat blood sugar
Annotate: * P＜0.05, compare with model control group * * P＜0.01; Compare with rosiglitazone with single #P＜0.05; Compare with vildagliptin with single $P＜0.05; ﹠amp; Compare with folic acid VB12 group P＜0.05.
Experimental result is as shown in table 3, and model group blood glucose significantly raises, and vildagliptin, rosiglitazone list are used all significantly blood sugar lowering, and folic acid VB12 uses does not have obvious effect to blood glucose; Vildagliptin and rosiglitazone share significantly blood sugar lowering, share to be better than arbitrary medicine list usefulness; Vildagliptin, rosiglitazone, folic acid VB12 compositions have remarkable blood sugar reducing function, are better than arbitrary single medicine, and be not remarkable to the advantageous effect of vildagliptin and rosiglitazone compound recipe.Above-mentioned experimental result explanation vildagliptin, rosiglitazone, folic acid VB12 compositions be blood sugar control better.
(2) vildagliptin, rosiglitazone, folic acid VB12 compositions are to the influence of 24h urine protein and blood plasma NO
Table 4 vildagliptin, rosiglitazone, folic acid VB12 compositions are to the influence of 24h urine protein and blood plasma NO
Annotate: * P＜0.05, compare with model control group * * P＜0.01; #P＜0.05 is organized relatively with rosiglitazone+folic acid VB12; $P＜0.05 is organized relatively with vildagliptin+folic acid VB12; ﹠amp; Compare with vildagliptin+rosiglitazone group P＜0.05.
Experimental result is as shown in table 4, and the model group urine protein significantly raises, and single medicine group all has a declining tendency, but all not remarkable; Rosiglitazone+folic acid VB12 group, vildagliptin+folic acid VB12 group can significantly reduce urine protein, this shows, folic acid VB12 has certain effect at tool aspect the protection kidney; Vildagliptin+rosiglitazone group also can significantly reduce urine protein; and vildagliptin, rosiglitazone, the effect of folic acid VB12 compositions are the most obvious; significantly be better than model group, rosiglitazone+folic acid VB12 group, vildagliptin+folic acid VB12 group and vildagliptin+rosiglitazone group, the effect that has collaborative renal function protecting between vildagliptin, rosiglitazone, three components of folic acid VB12 compositions is described.
Model group blood plasma NO significantly reduces, and single medicine group all has trend of rising, but all not remarkable; Rosiglitazone+folic acid VB12 group, vildagliptin+folic acid VB12 group be elevation of NO significantly; this shows; folic acid VB12 has protective effect aspect the protection endotheliocyte; vildagliptin+rosiglitazone group is remarkable elevation of NO also; and vildagliptin, rosiglitazone, the effect of folic acid VB12 compositions are the most obvious; significantly be better than model group, rosiglitazone+folic acid VB12 group, vildagliptin+folic acid VB12 group and vildagliptin+rosiglitazone group, the effect that has collaborative protection endotheliocyte between vildagliptin, rosiglitazone, three components of folic acid VB12 compositions is described.
The invention provides a kind of hypoglycemic medicine composition and uses thereof, this hypoglycemic medicine composition comprises (1) vildagliptin; (2) any one in thiazolidinediones antidiabetic drug or its officinal salt, sulfonylureas drugs for diabetes or its officinal salt or biguanides antidiabetic drug or its officinal salt or combination in any; 3) vitamin B group.This hypoglycemic medicine composition is blood sugar control effectively; the coordinating protection inner skin cell function; alleviate diabetics and particularly be associated with the diabetics homocysteine in plasma rising of chronic complicating diseases, and can reduce the generation of diabetic complication, have synergy.Pharmaceutical composition provided by the invention is on the effective therapeutic effect of diabetes, beneficial effect with tangible prevent diabetes complication, therefore be antidiabetic medicine preferably, provide a kind of feasible, safe therapeutic scheme for treating and/or preventing diabetes or diabetic complication.
It should be noted last that, above embodiment is only unrestricted in order to technical scheme of the present invention to be described, although the present invention is had been described in detail with reference to preferred embodiment, those of ordinary skill in the art is to be understood that, can make amendment or be equal to replacement technical scheme of the present invention, and not break away from the spirit and scope of technical solution of the present invention.
Claims (16)
1. a hypoglycemic medicine composition is characterized in that, comprising:
1) vildagliptin of pharmaceutical dosage;
2) biguanides of the sulphanylureas of the thiazolidinediones of pharmaceutical dosage or its officinal salt, pharmaceutical dosage or its officinal salt or pharmaceutical dosage or any one or combination in any in its officinal salt;
3) vitamin B group.
2. hypoglycemic medicine composition according to claim 1 is characterized in that, also comprises pharmaceutically suitable carrier or excipient.
3. hypoglycemic medicine composition according to claim 1 is characterized in that, described vitamin B group is any one or the combination in any in folic acid, vitamin B12, the vitamin B6.
4. hypoglycemic medicine composition according to claim 3 is characterized in that, the pharmaceutical dosage of described folic acid is 0.1-7.5mg; The pharmaceutical dosage of described vitamin B12 is 0.005-2mg; The pharmaceutical dosage of described vitamin B6 is 2-75mg.
5. hypoglycemic medicine composition according to claim 1 is characterized in that, the pharmaceutical dosage of described vildagliptin is 25-200mg.
6. hypoglycemic medicine composition according to claim 5 is characterized in that, the pharmaceutical dosage of described vildagliptin is 50-100mg.
7. hypoglycemic medicine composition according to claim 1, it is characterized in that described thiazolidinediones antidiabetic drug or its officinal salt are any one or the combination in any in rosiglitazone, rosiglitazone maleate, pioglitazone, pioglitazone hydrochloride, troglitazone, englitazone or the ciglitazone.
8. hypoglycemic medicine composition according to claim 7 is characterized in that, described thiazolidinediones antidiabetic drug is specially at least a in rosiglitazone and the pioglitazone, and the pharmaceutical dosage of described rosiglitazone is 1-8mg; The pharmaceutical dosage of described pioglitazone is 7.5-45mg.
9. hypoglycemic medicine composition according to claim 1, it is characterized in that described sulfonylureas drugs for diabetes is any one or the combination in any in glibenclamide, glibornuride, glycyclamide, glyhexamide, glimepiride, glypinamide, glisamuride, Glisentide, glisolamide, glyoctamide, gliclazide, glipizide or the gliquidone.
10. hypoglycemic medicine composition according to claim 9 is characterized in that, described sulfonylureas drugs for diabetes is specially any one or the combination in any in glibenclamide, glimepiride, gliclazide, glipizide or the gliquidone; The pharmaceutical dosage of described glibenclamide is 1-15mg; The pharmaceutical dosage of described glimepiride is 1-4mg; The pharmaceutical dosage of described gliclazide is 20-160mg; The pharmaceutical dosage of described glipizide is 1-15mg; The pharmaceutical dosage of described gliquidone is 15-60mg.
11. hypoglycemic medicine composition according to claim 1 is characterized in that, described biguanides antidiabetic drug is any one or the combination in any in metformin, phenformin or the buformin.
12. hypoglycemic medicine composition according to claim 11 is characterized in that, described biguanides antidiabetic drug is specially metformin, and the pharmaceutical dosage of metformin is 125-2000mg.
13. hypoglycemic medicine composition according to claim 12 is characterized in that, the pharmaceutical dosage of described metformin is 500-100mg.
14. pharmacy dosage form that comprises each described hypoglycemic medicine composition of claim 1 to 12, it is characterized in that, comprise conventional tablet, bilayer tablet, multilayer tablet, slow releasing tablet, the single chamber controlled release tablet, two chambers controlled release tablet, the pore type controlled release tablet, sublingual lozenge, oral cavity quick disintegrating slice, dispersible tablet, enteric coatel tablets, granule, pill, enteric coated capsule, delayed-release tablet, regularly/the position releasing piece, conventional capsule, slow releasing capsule, controlled release capsule, the capsule that contains micropill or small pieces, the pH dependent form capsule that contains micropill or small pieces, oral liquid, membrane or patch.
15. each described hypoglycemic medicine composition of claim 1 to 12 treats and/or prevents purposes in diabetes or the diabetes complicated disease drug in preparation.
16. purposes according to claim 15, it is characterized in that, described diabetic complication comprises chronic complicating diseases and acute complications, and wherein chronic complicating diseases comprises diabetes cardiovascular complication, diabetic nephropathy, diabetic neuropathy, diabetic renal papillary necrosis, diabetic foot, diabetic dermopathy etc.
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| CN105287551A (en) * | 2015-09-23 | 2016-02-03 | 成都艾比科生物科技有限公司 | Compound preparation for lowering blood glucose |
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