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Therapeutic or prophylactic agent for diabetes

A technology of preventive medicine and diabetes, which is applied in the fields of medical formula, metabolic diseases, drug delivery, etc., can solve the problems of different diseases and unrecorded treatment effects of diabetes, and achieve the effect of high effectiveness

Inactive Publication Date: 2013-11-13
TORAY IND INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, it has been found that beraprost sodium is effective for diabetic complications such as arteriosclerosis, diabetic nephropathy, diabetic small vessel disorder, diabetic neuropathy, diabetic retinopathy, and diabetic macrovascular disorder (Patent Document 8) , or by combining beraprost sodium with a diabetes treatment drug, nerve conduction velocity can be improved for motor nerve and sensory nerve dysfunction that cannot be sufficiently treated with existing diabetes treatment drugs, and it is disclosed that the combination of the above drugs is used to treat Method for treating diabetic neuropathy (Patent Document 9)
However, the target diseases of the above-mentioned reports are different, and there is no description about the therapeutic effect of diabetes by the combination of beraprost sodium and diabetes therapeutic drugs
On the other hand, it has been disclosed that beraprost sodium and pioglitazone hydrochloride are effective for treating or preventing diabetes (patent document 3), but in this document, beraprost sodium and pioglitazone hydrochloride are only used as IP Agonists and PPAR- gamma Listed as one of several drug combinations of agonists, with no specific documentation of the effect or confirmation of the effect of the combination of the two at all
[0009] However, regarding the IP agonist as a role in attenuating the PPAR- gamma Therapeutic or preventive drugs for diabetes that have excellent blood sugar lowering effects in addition to the side effects of agonists, that is, weight gain, have not been known so far

Method used

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  • Therapeutic or prophylactic agent for diabetes
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  • Therapeutic or prophylactic agent for diabetes

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Experimental program
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preparation example Construction

[0081] The preparation method of pioglitazone or its pharmacologically acceptable salt is well-known, for example, it can prepare by the method described in JP Sho 55-22636 or JP Sho 61-267580. In addition, commercially available products can also be preferably used. It is usually used together with pharmacologically acceptable carriers or excipients in the form of ordinary pharmaceutical preparations such as tablets, capsules, powders, granules, liquid preparations, etc. that can be taken orally, but it is not particularly limited to these.

[0082] In the present invention, among the IP agonists, the compound represented by the general formula (I), especially beraprost sodium and PPAR- γ Among the agonists is the combination of pioglitazone hydrochloride.

[0083] In the present invention, "therapeutic or preventive drugs for diabetes" also include drugs that are both therapeutic and preventive drugs for diabetes.

[0084] The dosage of the therapeutic or preventive drug of the pr...

Embodiment 1

[0105] The combined effect of beraprost sodium (BPS) and pioglitazone hydrochloride on blood glucose level and body weight of KKAy mice

[0106] Male KKAy mice (Kura Corporation, Japan) were used in the experiment. KKAy mice show obesity and hyperglycemia from 7 to 8 weeks old, and are widely used as type 2 diabetes model mice. KKAy mice were purchased at 5 weeks of age, and were fed with CMF feed (Oriental Yeast Industry Co., Ltd.) for 3 weeks in an environment of free food and water intake from the time of purchase, and then supplied to the experiment. For continuous subcutaneous administration of solvents (normal saline, 6 μ L / day) or BPS (1mg / kg / day, commercially available from Toray Company), indwelling sustained-release micropumps (Alzet micro-osmotic pump 1002 type, Alzet osmotic pumps company) under the skin of KKAy mice . It should be noted that the administration of saline or BPS was continued until the end of the experiment. Three days after the indwelling treatme...

Embodiment 2

[0127] The effect of beraprost sodium (BPS) and pioglitazone hydrochloride on the sugar tolerance of KKAy mice

[0128] Male KKAy mice (Kura Corporation, Japan) were used in the experiment. KKAy mice were purchased at 5 or 7 weeks of age, and were fed CMF feed (Oriental Yeast Industry Co., Ltd.) in an environment of free food and water intake for 2 to 4 weeks from the time of purchase. After grouping, the oral administration of solvent (0.5% methyl cellulose (MC) solution, 10 mL / kg) or pioglitazone hydrochloride (Toray's internal synthetic product) was started. Pioglitazone hydrochloride is administered as a 0.5% MC suspension solution. The administration period of MC solution and pioglitazone hydrochloride were both 20 days, and the administration was performed once a day in the evening. Six days after the start of administration of MC solution and pioglitazone hydrochloride, in order to continue subcutaneous administration of solvents (physiological saline, 6 μ L / day) or BP...

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Abstract

A therapeutic or prophylactic agent for diabetes comprising a thiazolidine derivative as a PPAR-³ agonist as an effective component, which agent shows a reduced side effect of the PPAR-³ agonist, is disclosed. The therapeutic or prophylactic agent for diabetes comprises a particular IP agonist such as beraprost sodium (BPS), and a thiazolidine derivative such as pioglitazone or a pharmaceutically acceptable salt thereof. Since the therapeutic or prophylactic agent of the present invention shows a sufficiently effective hypoglycemic action without being accompanied by side effects characteristic to PPAR-³ agonists (e.g., body weight gain), the agent is useful as a highly safe and effective therapeutic or prophylactic agent for diabetes.

Description

Technical field [0001] The present invention relates to a medicine for treating or preventing diabetes with reduced side effects. Background technique [0002] Diabetes is a group of diseases characterized by chronic hyperglycemia accompanied by insufficient insulin action and accompanied by various characteristic metabolic abnormalities. The number of patients in the world has shown an increasing trend, especially with lifestyle changes such as high-fat diet and insufficient exercise, combined with obesity, hypertriglyceridemia, low HDL-cholesterolemia, abnormal glucose metabolism, and hypertension Diabetes patients with metabolic syndrome type 2 and other risk factors are increasing. In this context, it is known that insulin resistance (insufficient insulin action) is strongly intervening, and therefore, there is a strong desire to develop a type 2 diabetes treatment agent showing an effect of improving insulin resistance. [0003] Peroxisome proliferator-responsive receptor as...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/4439A61K31/343A61P3/04A61P3/10A61P43/00
CPCA61K31/343A61K31/5575A61K31/4439A61P3/04A61P3/10A61P31/10A61P43/00A61K2300/00A61K9/0053
Inventor 高桥雄大熊谷洋纪门胁孝洼田直人洼田哲也
Owner TORAY IND INC