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Combination product comprising limonoids and sulfonylurea

A technology of limonoids and combination products, applied in the field of medicine, can solve the problems of liver and kidney toxicity, easy emergence of drug resistance, hypoglycemia and the like

Active Publication Date: 2019-10-08
NATURAL MEDICINE INST OF ZHEJIANG YANGSHENGTANG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, oral hypoglycemic drugs mainly include: sulfonylureas, biguanides, α-glucosidase inhibitors, thiazolidinediones, DPP-4 inhibitors, etc., but the oral hypoglycemic drugs are prone to drug resistance Sexuality, hypoglycemia, liver and kidney toxicity and other serious side effects

Method used

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  • Combination product comprising limonoids and sulfonylurea
  • Combination product comprising limonoids and sulfonylurea
  • Combination product comprising limonoids and sulfonylurea

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] The effect of limonin compounds, glibenclamide or their combination on blood glucose in mouse pancreatic islet β cell injury model

[0035] In this example, ICR mice were modeled with streptozotocin (STZ) to obtain a mouse pancreatic islet β cell injury model (Li Nan et al. Protective effect of pine pollen on kidney injury in diabetic nephropathy mice, Science and Technology Review, 2014, 32 (4 / 5): 95-99), complete the animal hypoglycemic efficacy evaluation experiment (this model can simulate the state of pancreatic islet β cell damage in type I and type II diabetes). Limonin compounds are selected from limonin, isocitrolactone acid, limonin glycosides, and isocitrolactone acid glycosides, and a separate glibenclamide administration group, limonin administration group, and isocitrin The acid administration group, the limonin glycoside administration group, the isocitrolactone acid glycoside administration group and the combined administration group compounded with glibenc...

Embodiment 2

[0046] The effect of limonin compounds, gliclazide or their combination on blood glucose and leptin in type II diabetes mouse model

[0047] In this example, db / db mice (strain name BKS.Cg-Dock7 m+ / + Lepr db / Nju) Complete the animal hypoglycemic effect evaluation experiment (blood sugar level and leptin). Limonin compounds choose corkone, isoflavone acid and corkone glycosides, and set up separate gliclazide administration group, corkone administration group, isoflavone acid administration group, and corkone glycoside administration group respectively And the combined administration group with Gliclazide.

[0048] Experimental breeding conditions: As a type II diabetes model mouse, 6-week-old SPF-grade db / db mice were purchased from Nanjing Model Biology Institute, and the experimental breeding was carried out after 7 days of preliminary breeding. It should be noted that the breeding conditions for the mice are temperature 23±1°C, humidity 55±10%, light on between 7 am and 7 pm ...

Embodiment 3

[0059] The effect of limonin compounds, glipizide or their combination on blood glucose in mouse pancreatic islet β cell injury model

[0060] In this example, ICR mice were modeled with streptozotocin (STZ) to obtain a mouse pancreatic islet β cell injury model (Li Nan et al. Protective effect of pine pollen on kidney injury in diabetic nephropathy mice, Science and Technology Review, 2014, 32 (4 / 5): 95-99), complete the animal hypoglycemic efficacy evaluation experiment (this model can simulate the state of pancreatic islet β cell damage in type I and type II diabetes). Limonin compounds choose Yichang aurantine, Yichang aurantine, and Yichang aurantine glycosides, and set up separate glipizide administration group, Yichang aurantine administration group, Yichang aurantine administration group, Yichang aurantine administration group The glycoside administration group and the combined administration group combined with glipizide.

[0061] Experimental breeding conditions: ICR mic...

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Abstract

The invention relates to a combination product comprising limonoids (pharmacologically acceptable derivatives, esters, steric isomers, salt or prodrugs) and sulfonylurea (such as glibenclamide, gliclazide, glipizide, gliquidone and glimepiride). The invention further relates to an application of the combination product to treatment and / or prevention of diabetes-related diseases and the like.

Description

Technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to a compound containing limonin (and its pharmaceutically acceptable derivatives, esters, stereoisomers, salts or prodrugs) and a sulfonylurea drug (or its pharmaceutical Acceptable derivatives). The invention also relates to the use of the combination product in the treatment and / or prevention of diabetes and metabolic syndrome related diseases. Background technique [0002] According to IDF statistics, there were approximately 425 million people with diabetes worldwide in 2017, and 1 out of 11 people has diabetes. The number of diabetes patients in China is about 110 million, ranking first in the world. It is predicted that by 2040, there will be 642 million people with diabetes in the world, and 151 million people with diabetes in China will also. Diabetes requires lifelong monitoring and treatment. If it is not well controlled, it will lead to secondary cardiovascular...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/585A61K31/64A61P3/10A61P3/00
CPCA61K45/06A61K31/585A61K31/64A61P3/10A61P3/00A61K2300/00A61K31/7048A61K31/366A61K9/2054
Inventor 李栋韩铨胡柳薛莲
Owner NATURAL MEDICINE INST OF ZHEJIANG YANGSHENGTANG
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