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Combination product containing limonin compound and DPP-4 inhibitors

A technology of limonoids and DPP-4, applied in the field of medicine, can solve problems such as drug resistance, hypoglycemia, liver and kidney toxicity, etc.

Active Publication Date: 2019-10-11
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 , hypoglycemia, liver and kidney toxicity and other serious side effects

Method used

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  • Combination product containing limonin compound and DPP-4 inhibitors
  • Combination product containing limonin compound and DPP-4 inhibitors
  • Combination product containing limonin compound and DPP-4 inhibitors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Effects of limonoids, sitagliptin or their combination on blood glucose in mouse islet β-cell injury model

[0036] In this example, ICR mice were modeled with streptozotocin (STZ) to obtain a mouse islet β-cell injury model (Li Nan et al., The protective effect of pine pollen on kidney damage in mice with diabetic nephropathy, Science and Technology Herald, 2014, 32 (4 / 5): 95-99), completed the animal hypoglycemic efficacy evaluation experiment (this model can simulate type I and type II diabetes islet β cell damage state). Limonoid compounds select limonin, isocitrin acid, limonin glycoside, and isocitrolactone glycoside, and set up a separate sitagliptin administration group, limonin administration group, and isocitrolactone administration group. acid administration group, limonin glycoside administration group, isocitrolactin acid glycoside administration group and combined administration group compounded with sitagliptin.

[0037] Experimental feeding conditions: ...

Embodiment 2

[0047] Effects of limonoids, saxagliptin or their combination on blood glucose and leptin in a mouse model of type II diabetes

[0048] In this embodiment, db / db mice (strain name BKS.Cg-Dock7 m+ / + Lepr db / Nju) completed the animal hypoglycemic efficacy evaluation experiment (blood sugar level and leptin). For the limonoid compounds, choose phellodendron, isofordone acid, and phellodendron glucoside, and set up separate saxagliptin administration groups, phellodendron administration groups, isofordone acid administration groups, and phellodendron glucoside administration groups. And the combined administration group with saxagliptin respectively.

[0049] Experimental feeding conditions: as type II diabetes model mice, 6-week-old SPF-grade db / db mice were purchased from the Nanjing Institute of Model Organisms, and the experimental feeding was carried out after 7 days of preparatory feeding. It should be noted that the feeding conditions of the mice were temperature of 23±...

Embodiment 3

[0060] Effects of limonoids, vildagliptin or their combination on blood glucose in mouse islet β-cell injury model

[0061] In this example, ICR mice were modeled with streptozotocin (STZ) to obtain a mouse islet β-cell injury model (Li Nan et al., The protective effect of pine pollen on kidney damage in mice with diabetic nephropathy, Science and Technology Herald, 2014, 32 (4 / 5): 95-99), completed the animal hypoglycemic efficacy evaluation experiment (this model can simulate type I and type II diabetes islet β cell damage state). Limonoid compounds choose Yichang Hesin, Yichang Genxin, and Yichang Hesin Glycoside, and set up separate Vildagliptin administration group, Yichang Hesin administration group, Yichang Genxin administration group, Yichang Hesin Veldagliptin administration group and combination administration group compounded with vildagliptin.

[0062] Experimental feeding conditions: ICR mice (20±2g), 6 weeks old, were purchased from Zhejiang Academy of Medical S...

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Abstract

The invention relates to a combination product of a limonin compound, pharmaceutically-acceptable derivatives, esters, stereoisomers, salts or prodrugs thereof and dipeptidyl peptidase-4(DPP-4) inhibitors such as sitagliptin, saxagliptin, vildagliptin, linagliptin, alogliptin, trelagliptin and omarigliptin. The invention further relates to application of the combination product in treating and / orpreventing diseases related to diabetes.

Description

technical field [0001] The invention belongs to the technical field of medicine, in particular to a limonoid compound (and pharmaceutically acceptable derivatives, esters, stereoisomers, salts or prodrugs thereof) and a DPP-4 inhibitor (or its pharmaceutical Combination products of acceptable derivatives above). The present invention also relates to the use of the combined product in treating and / or preventing diabetes and diseases related to metabolic syndrome. Background technique [0002] According to IDF statistics, there were about 425 million people with diabetes worldwide in 2017, and 1 in every 11 people has diabetes. The number of diabetic 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 worldwide, and 151 million people with diabetes in China. Diabetes requires lifelong monitoring and treatment. If it is not well controlled, it will lead to secondary cardiovascular di...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/585A61K31/513A61P3/10A61P3/00
CPCA61K45/06A61K31/585A61K31/513A61P3/10A61P3/00A61K2300/00A61K31/4985A61K31/366A61K31/7048A61K31/522A61K31/40A61K31/403A61K31/4162A61K9/2013A61K9/2095A61K9/2054A61K31/506
Inventor 李栋王威胡柳薛莲
Owner NATURAL MEDICINE INST OF ZHEJIANG YANGSHENGTANG
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