Application of butylphthalide or derivatives thereof in preparation of medicaments for promoting angiogenesis

A technology of butylphthalide and angiogenesis, which is applied in the direction of drug combination, cardiovascular system diseases, active ingredients of heterocyclic compounds, etc., can solve the problems of not teaching butylphthalide, etc., and achieve the improvement of antioxidant enzyme activity and definite curative effect , quick effect

Inactive Publication Date: 2012-05-16
SHIJIAZHUANG PHARMA GRP NBP PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] However, the prior art does not teach that butylphth

Method used

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  • Application of butylphthalide or derivatives thereof in preparation of medicaments for promoting angiogenesis
  • Application of butylphthalide or derivatives thereof in preparation of medicaments for promoting angiogenesis
  • Application of butylphthalide or derivatives thereof in preparation of medicaments for promoting angiogenesis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Example 1 Pro-angiogenic effect of butylphthalide on transgenic zebrafish

[0046] (1) Materials and methods

[0047] 1. Drug: Butylphthalide, colorless to pale yellow oily liquid. Soluble in DMSO, the storage concentration is 80mmol / L, and stored at -20°C for later use.

[0048] 2. Fli 1-EGFP Transgenic Zebrafish Rearing and Embryo Collection

[0049] Sexually mature transgenic zebrafish are about 3 months old. Fully automated temperature control, light control, water treatment, and circulating zebrafish breeding system are used for daily maintenance of adult fish. The water temperature is 28.5°C, pH is about 7.0, and the day and night time is alternated for 12 hours. The hatched brine shrimp and tropical fish feed are cross-fed. Prepare injection plates with 2% agarose. One female and one male transgenic zebrafish were placed in a plastic tank, and the transparent barrier separated the male and female fish to prevent them from mating and laying eggs. Let each pai...

Embodiment 2

[0061] Example 2 The angiogenesis-promoting effect of butylphthalide on human umbilical vein endothelial cells

[0062] (1) Materials and methods

[0063] 1. Drug: Butylphthalide, colorless to pale yellow oily liquid. Soluble in DMSO, the storage concentration is 80mmol / L, and stored at -20°C for later use.

[0064] 2. Culture and experimental grouping of human umbilical vein endothelial cells

[0065] Human umbilical vein endothelial cells (HUVEC) were cultured in F-12K at 37°C in 5% CO 2 cultured in an incubator. The cell culture flask and the 24-well plate used in the experiment were covered with a layer of 0.1% gelatin before use, and 2-5 passages were used in the experiment. The experiment was divided into positive control group (VEGF), butylphthalide group and control group. The positive control group contained 20ng / ml VEGF and 0.1 volume% DMSO, the butylphthalide group was set as 10, 50, 100, 150, 200uM / ml 5 dosage groups, and the control group only added 0.5 volum...

Embodiment 3

[0082] Example 3 Study on Mechanism of Butylphthalide Promoting Angiogenesis

[0083] (1) Materials and methods

[0084] 1. Drug: Butylphthalide, colorless to pale yellow oily liquid. Soluble in DMSO, the storage concentration is 80mmol / L, and stored at -20°C for later use.

[0085] 2. The raising of fli 1-EGFP transgenic zebrafish and the collection of embryos: the same as in Example 1.

[0086] 3. Drug handling and grouping

[0087] The experiment was divided into fish water group, 0.2 volume% DMSO group, 10uM / L SU5402 group, 10uM / L SU5416 group, 100uM / L butylphthalide+10uM / L SU5402 group, 100uM / L butylphthalide+10uM / L SU5416 group, 100uM / L butylphthalide group. When the embryos split to the 16-256 cell stage, fish eggs were randomly placed in 96-well culture plates (U bottom). Load 3 embryos and 200ul of fish water (40g of instant sea salt plus 1000ml of distilled water) into each well, and add the sample at 6hpf (hourpostfertilized, hours after fertilization). Cultur...

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Abstract

The invention discloses application of butylphthalide or derivatives thereof in preparation of medicaments for promoting angiogenesis. According to the invention, butylphthalide and derivatives thereof have significant actions of promoting angiogenesis to a transgenic zebra fish model of which green fluorescent protein is expressed by blood vessel endotheliocyte surface and an in-vitro cultured human umbilical vein endotheliocyte model, thus can be used for preparing the medicaments for promoting angiogenesis and has potential value in application to other ischemic related diseases.

Description

technical field [0001] The invention relates to the field of medicine application, in particular to the application of butylphthalide or its derivatives in the preparation of medicines for promoting angiogenesis. Background technique [0002] Angiogenesis is a complex process of generating new blood vessels by stimulating the budding of endothelial cells to form small blood vessel growth and collateral circulation in the surrounding tissue on the basis of the original vascular network. This process involves multiple steps such as the degradation of vascular endothelial extracellular matrix, migration of endothelial cells to the degraded matrix, proliferation, stretching, formation of tubular structures, and production of endothelial extracellular matrix membrane. It mainly includes: degradation of vascular basement membrane in the activation phase; Activation, proliferation, migration; reconstruction of new blood vessels and vascular network is a complex process involving a ...

Claims

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Application Information

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IPC IPC(8): A61K31/365A61K31/5375A61K31/445A61K31/235A61K31/192A61P9/00A61P9/10
Inventor 黄如训裴中卢锡林曾进胜王冠蕾区景松郭海波
Owner SHIJIAZHUANG PHARMA GRP NBP PHARMA CO LTD
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