CN102362866A - Medicinal composition for treating diabetes and obesity - Google Patents
Medicinal composition for treating diabetes and obesity Download PDFInfo
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- CN102362866A CN102362866A CN2011103700670A CN201110370067A CN102362866A CN 102362866 A CN102362866 A CN 102362866A CN 2011103700670 A CN2011103700670 A CN 2011103700670A CN 201110370067 A CN201110370067 A CN 201110370067A CN 102362866 A CN102362866 A CN 102362866A
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- sitagliptin
- simvastatin
- lovastatin
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- salt
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Abstract
The invention belongs to the technical field of medicinal preparations and particularly relates to a medicinal composition for treating diabetes and obesity and preparation and use thereof. The invention is characterized in that the active ingredient of a single dose of medicine comprises 10 to 90 milligrams of Sitagliptin or salt thereof based on Sitagliptin and 5 to 50 milligrams of Simvastatin or Lovastatin, preferably 25 to 50 milligrams of Sitagliptin or salt thereof and 5 to 25 milligrams of Simvastatin or Lovastatin. The medicinal composition can be prepared into any formulation acceptable in pharmaceutics, preferably oral solid preparation.
Description
Technical field
The invention belongs to technical field of pharmaceuticals, be specifically related to a kind of pharmaceutical composition of treating diabetes and obesity, its active component consists of sitagliptin and simvastatin/lovastatin.
Background technology
Sitagliptin (Sitagliptin), another name (3R)-3-amino-1-[3-(trifluoromethyl)-5,6,7,8-tetrahydrochysene-1,2,4-triazol [4,3-a] pyrazine-7-yl]-4-(2 ,-trifluorophenyl) fourth-1-ketone, the clinical type 2 diabetes mellitus that is used for.This medicine is dipeptidyl peptidase-4 (DPP-4) depressant, through protecting the endogenous incretin and strengthening its effect and glucose level control.Glucose dependency insulinotropic peptide (GIP) and glucagon-like-peptide-1 (GLP-1) are to take in and the incretin of release to meals.GLP-1 and GIP can increase the synthetic release that reaches from beta Cell of islet of insulin through signal pathway in the cell, and GLP-1 also can reduce islets of langerhans a emiocytosis glucagon, hepatic glucose is generated reduce.But GLP-1 and GIP cause its pancreotropic hormone effect forfeiture by the DPP-4 tachymetabolism.This medicine suppresses the degraded of incretin through DPP-4, so can strengthen the function of GLP-1 and GIP, increases insulin release and reduces glucagon level (this effect is the glucose dependency) in the circulation.This medicine selectivity suppresses DPP-4, and is active to DPP-8 or DPP-9 unrestraint.The clinical salt sitagliptin phosphate that also often uses sitagliptin.
Simvastatin and lovastatin suppress the synthetic of endogenous cholesterol, are blood ester regulator.Clinically be used to treat hypercholesterolemia, coronary heart disease.These article are methyl hydroxyl glutaryl coenzyme A (HMG-COA) reductase inhibitor, suppress the synthetic of endogenous cholesterol, are lipid regulating agent.Documents and materials show that the content that reduces cholesterol (TC) in hyperlipemia rabbit anteserum, liver, the aorta is arranged, and reduce C-VLDL (VLDL-C), the effect of low-density lipoprotein cholesterol (LDL-C) level.
Though prior art has the combination that in hypoglycemic drug, adds hypolipidemic at present, this combination mainly is a hyperlipidemia complication of considering that the hyperglycemia disease is brought.
Summary of the invention
The applicant is unexpected under study for action to be found; Sitagliptin or its salt and simvastatin or lovastatin combination used to produce the effect of Synergistic treatment diabetes; Compare with only using sitagliptin, the adding of simvastatin or lovastatin makes the therapeutic effect of compositions obtain unexpected significantly improving.
Also find simultaneously this good effect that also has when being combined in treatment of obesity.
The present invention relates to a kind of pharmaceutical composition of treating diabetes and obesity, it is characterized in that its active component composition is in sitagliptin sitagliptin or its salt 10-90mg, simvastatin or lovastatin 5-50mg.
Preferred sitagliptin or its salt 25-50mg, simvastatin 5-25mg.
Preferred sitagliptin or its salt 25-50mg, lovastatin 5-25mg.
Wherein sitagliptin or its salt can be hydrate forms.
Wherein sitagliptin salt can be phosphoric acid two Ta Lieting.
The application also relates to the purposes of aforementioned pharmaceutical compositions in the medicine of preparation treatment diabetes and obesity.
The application also relates to the preparation that aforementioned pharmaceutical compositions prepares.Its preparation formulation is an oral solid formulation.Its preparation formulation is conventional tablet, dispersible tablet, capsule or granule.
Above-mentioned sitagliptin also can substitute for other salt of sitagliptin.
Dosage form of the present invention can adopt the common process preparation of prior art.
Collaborative hypoglycemic activity experimentation
Supply the examination animal to be cleaning level Kunming mouse, male and female half and half, body weight 20-25g.
The preparation of diabetic mice: get Kunming mouse; Male and female half and half; Alloxan is mixed with 2% injection; According to alloxan 200mg/kg dosage the mice of fasting 12h is carried out lumbar injection, raises after 3 days, cut the tail blood sampling measure fasting glucose greater than 14mmol/L as diabetic mice.
Diabetic mice is divided into 10 groups, 6 every group, promptly tests medicine 1-4 group and contrast 1-5 group, model control group; Blank control group is set in addition.Model control group not administration behind the modeling type only gives distilled water; Blank control group is not then injected alloxan in modeling the time, only inject the equivalent normal saline.The drug regimen mediating recipe measuring that experiment medicine 1-4 group and contrast 1-4 group are used is following:
1 group of experiment medicine: drug regimen is: sitagliptin phosphate (in sitagliptin) 25mg, simvastatin 5mg;
2 groups of experiment medicines: drug regimen is: sitagliptin phosphate (in sitagliptin) 25mg, simvastatin 25mg
3 groups of experiment medicines: drug regimen is: sitagliptin phosphate (in sitagliptin) 50mg, simvastatin 5mg
4 groups of experiment medicines: drug regimen is: sitagliptin phosphate (in sitagliptin) 50mg, simvastatin 25mg
Contrast 1 group: sitagliptin phosphate (in sitagliptin) 25mg
Contrast 2 groups: sitagliptin phosphate (in sitagliptin) 50mg
Contrast 3 groups: sitagliptin phosphate (in sitagliptin) 100mg
Contrast 4 groups: simvastatin 5mg
Contrast 5 groups: simvastatin 25mg
The dosage unit that the sign consumption behaviour single of above-mentioned experiment medicine 1-4 group and contrast 1-5 group uses; During actual gastric infusion above-mentioned dosage being converted to corresponding mice dosage respectively by pharmacology's animal body surface area dose translation method carries out; Each organizes 2 weeks of gastric infusion, once a day.After treatment finished, each treated animal fasting was after 12 hours, and the tail blood sampling detects the FBG level before morning next day.
Blood sugar level compares (sitagliptin+simvastatin) before and after the administration of table 1 different experiments treated animal
*P＜0.05,
*Compare with model control group P＜0.01;
#Compare for 1 or 2 or 3 group with contrast P＜0.05
Experimental result shows that the present invention has hypoglycemic activity when contrasting list with sitagliptin; But the simvastatin list time spent does not have blood sugar decreasing effect; And four groups of administration group promptly when the combination of sitagliptin and simvastatin is used its hypoglycemic activity obviously strengthen; With single remarkable with the sitagliptin comparative effectiveness, because simvastatin itself does not have hypoglycemic activity basically, description the application's pharmaceutical composition has played collaborative hypoglycemic activity.
Based on above-mentioned experiment basis, the applicant selects to substitute the same experiment of simvastatin with lovastatin, and experimental technique is with the experiment of above-mentioned simvastatin, and the result shows that it also can play synergism, sees table 2.Wherein contrasting 1 group is: lovastatin 5mg; Contrast 2 groups: lovastatin 25mg;
1 group of experiment medicine: drug regimen is: sitagliptin phosphate (in sitagliptin) 25mg, lovastatin 5mg;
2 groups of experiment medicines: drug regimen is: sitagliptin phosphate (in sitagliptin) 25mg, lovastatin 25mg
3 groups of experiment medicines: drug regimen is: sitagliptin phosphate (in sitagliptin) 50mg, lovastatin 5mg
4 groups of experiment medicines: drug regimen is: sitagliptin phosphate (in sitagliptin) 50mg, lovastatin 25mg
Blood sugar level compares (sitagliptin+lovastatin) before and after the administration of table 2 different experiments treated animal
*The model control group data of P＜0.01 and table 1 relatively;
#Compare for 1 or 2 group with contrast P＜0.01.
Because lovastatin itself do not have blood sugar decreasing effect, and four groups of administration group promptly when sitagliptin uses with the lovastatin combination its hypoglycemic activity and list obviously strengthen with sitagliptin, explain that the application's pharmaceutical composition has played collaborative hypoglycemic activity.
Treatment of obesity effect research
Active component itself in the known above-mentioned composition of prior art is that not have treatment of obesity be the controlling body weight effect for sitagliptin and simvastatin, lovastatin; Just be used for the relevant diabetes of obesity or the control of blood fat, find that the application's drug regimen also has the effect of better controlling obesity and the applicant is also unexpected in to the research of above-mentioned composition.
The reference literature method is set up fat model:
Normal feedstuff: Fructus Hordei Vulgaris powder 20%, dehydration cabbage 10%, Semen Glycines powder 20%, Semen Maydis powder 16%, yeast 1%, wheat bran 16%, fish flour 10%, bone meal 5%, salt 2%.
High fat material: in normal feedstuff 100g, add 10 of milk powder 10g, Adeps Sus domestica 10g, 1 in egg, fresh bean sprout 250g, cleum jecoris piscis concentratum.
Under normal diet and the condition of freely drinking water, adaptability raising 3d is divided into normal control group (10) and high lipid food group according to body weight then at random with rat children mouse (initial body weight 40-50g).Each is organized rat and every day enough food is provided, and freely drinks water, and surveys the body constitution amount weekly 1 time, feeds for 4 weeks continuously.The high lipid food group (exceeding the normal group body weight more than 20%) of getting successfully modeling is divided into fat model group (10) and administration group (10 of every administration groups), feeds for 4 weeks continuously, and except that the normal control group was fed normal diet, other groups all gave high lipid food.The administration group obtains according to people's dosage and after converting.Experimental result is seen table 3.The drug regimen of wherein administration group is respectively:
1 group of experiment medicine: drug regimen is: sitagliptin phosphate (in sitagliptin) 25mg, simvastatin 5mg;
2 groups of experiment medicines: drug regimen is: sitagliptin phosphate (in sitagliptin) 25mg, simvastatin 25mg
3 groups of experiment medicines: drug regimen is: sitagliptin phosphate (in sitagliptin) 50mg, simvastatin 5mg
4 groups of experiment medicines: drug regimen is: sitagliptin phosphate (in sitagliptin) 50mg, simvastatin 25mg
5 groups of experiment medicines: drug regimen is: sitagliptin phosphate (in sitagliptin) 25mg, lovastatin 5mg;
6 groups of experiment medicines: drug regimen is: sitagliptin phosphate (in sitagliptin) 25mg, lovastatin 25mg
7 groups of experiment medicines: drug regimen is: sitagliptin phosphate (in sitagliptin) 50mg, lovastatin 5mg
8 groups of experiment medicines: drug regimen is: sitagliptin phosphate (in sitagliptin) 50mg, lovastatin 25mg
Body weight change before and after the administration of table 3 different experiments treated animal
Compare with model control group
*P＜0.01
Experimental result shows the relatively obviously body weight gain of controlling obesity rat of pharmaceutical composition administration group of the present invention and model control group; Help the treatment and the control of obesity; Because the active medicine of compositions itself is not direct controlling body weight medicine, explain the application the drug regimen deposits yields the unforeseen effect of prior art.
Preparation embodiment
The preparation of the application's pharmaceutical composition can prepare according to the prior art conventional method, and preparation embodiment is merely exemplary, and the dosage form that is fit to above-mentioned active component arbitrarily can be selected.
Embodiment 1
Sitagliptin phosphate (in sitagliptin) 25g, simvastatin 5g;
Method for preparing: be prepared into 1000 in tablet by conventional method with above-mentioned active component.
Embodiment 2
Sitagliptin phosphate 25g (in sitagliptin), simvastatin 25g;
Method for preparing: be prepared into 1000 of capsules with above-mentioned active component.
Embodiment 3
Sitagliptin phosphate 50g (in sitagliptin), simvastatin 5g;
Method for preparing: prepare 1000 of dispersible tablets by conventional method with above-mentioned active component.
Embodiment 4
Sitagliptin phosphate 50g (in sitagliptin), simvastatin 25g;
Method for preparing: will prepare granule with above-mentioned active component by the preparation conventional method.
Embodiment 5
Sitagliptin phosphate (in sitagliptin) 25g, lovastatin 5g;
Method for preparing: be prepared into 1000 in tablet by conventional method with above-mentioned active component.
Embodiment 6
Sitagliptin phosphate 25g (in sitagliptin), lovastatin 25g;
Method for preparing: be prepared into 1000 of capsules with above-mentioned active component.
Embodiment 7
Sitagliptin phosphate 50g (in sitagliptin), lovastatin 5g;
Method for preparing: prepare 1000 of dispersible tablets by conventional method with above-mentioned active component.
Embodiment 8
Sitagliptin phosphate 50g (in sitagliptin), lovastatin 25g;
Method for preparing: will prepare granule with above-mentioned active component by the preparation conventional method.
Claims (9)
1. a pharmaceutical composition of treating diabetes and obesity is characterized in that its active component composition is in sitagliptin sitagliptin or its salt 10-90mg, simvastatin or lovastatin 5-50mg.
2. according to the pharmaceutical composition of claim 1, it is characterized in that its active component consists of: sitagliptin or its salt 25-50mg, simvastatin 5-25mg.
3. according to the pharmaceutical composition of claim 1, it is characterized in that its active component consists of: sitagliptin or its salt 25-50mg, lovastatin 5-25mg.
4. according to each pharmaceutical composition of claim 1-3, it is characterized in that sitagliptin or its salt are hydrate forms.
5. according to each pharmaceutical composition of claim 1-3, it is characterized in that sitagliptin salt is the phosphate of sitagliptin.
6. each the purposes of pharmaceutical composition in the medicine of preparation treatment diabetes and obesity of claim 1-5.
7. the preparation that obtains of each preparation of pharmaceutical compositions of claim 1-5.
8. according to the pharmaceutical preparation of claim 7, its preparation formulation is an oral solid formulation.
9. according to Claim 8 pharmaceutical preparation, its preparation formulation is conventional tablet, dispersible tablet, capsule or granule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103700670A CN102362866A (en) | 2011-11-21 | 2011-11-21 | Medicinal composition for treating diabetes and obesity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103700670A CN102362866A (en) | 2011-11-21 | 2011-11-21 | Medicinal composition for treating diabetes and obesity |
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| CN102362866A true CN102362866A (en) | 2012-02-29 |
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| CN2011103700670A Pending CN102362866A (en) | 2011-11-21 | 2011-11-21 | Medicinal composition for treating diabetes and obesity |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107303390A (en) * | 2017-01-22 | 2017-10-31 | 复旦大学附属华山医院 | Purposes of the DPP4 inhibitor in treatment Hypoxic Pulmonary Hypertension in Rats medicine is prepared |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102125560A (en) * | 2006-05-04 | 2011-07-20 | 贝林格尔·英格海姆国际有限公司 | Uses of DPP-IV inhibitors |
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- 2011-11-21 CN CN2011103700670A patent/CN102362866A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102125560A (en) * | 2006-05-04 | 2011-07-20 | 贝林格尔·英格海姆国际有限公司 | Uses of DPP-IV inhibitors |
Non-Patent Citations (1)
| Title |
|---|
| 孙谊: "域外资讯", 《中国食品药品监管》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107303390A (en) * | 2017-01-22 | 2017-10-31 | 复旦大学附属华山医院 | Purposes of the DPP4 inhibitor in treatment Hypoxic Pulmonary Hypertension in Rats medicine is prepared |
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| DD01 | Delivery of document by public notice |
Addressee: Zheng Feixiong Document name: Notification of Passing Preliminary Examination of the Application for Invention |
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| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20120229 |