Application of integrin blocker in preparation of medicaments for treating ocular neovascular diseases

An integrin blocker and new blood vessel technology, which can be used in cardiovascular system diseases, drug combinations, sensory diseases, etc., can solve problems such as deficiency, and achieve the effect of improving the formation of new blood vessels and reducing the effect of new blood vessel clusters

Active Publication Date: 2011-10-05
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Avastin has been successfully used in the treatment of eye diseases, but my country still lacks such drugs independently developed

Method used

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  • Application of integrin blocker in preparation of medicaments for treating ocular neovascular diseases
  • Application of integrin blocker in preparation of medicaments for treating ocular neovascular diseases
  • Application of integrin blocker in preparation of medicaments for treating ocular neovascular diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Inhibitory Effect of Integrin Blocker Peptides on the Proliferation of Human Retinal Vascular Endothelial Cells (HRCEC)

[0044] MTT assay was used to detect the inhibitory activity of integrin blocker polypeptide on the proliferation of human retinal vascular endothelial cells. HRCEC cells were incubated at 37°C, 5% CO 2 When cultured in an incubator with a density of more than 90%, it was digested with trypsin and collected, and the cells were resuspended in culture medium and counted under a microscope, and the cell concentration was adjusted to 3.0×10 4 cells / mL, seed the cell suspension into a 96-well plate, 100 μL per well, and inoculate at 37°C, 5% CO 2 Incubate overnight in the incubator. Dilute the polypeptide I, polypeptide II, polypeptide III, and Avastin to respective predetermined concentrations with culture medium. After the cells were completely attached to the wall, each dilution was added to a 96-well plate, 100 μL per well. The addition of integrin...

Embodiment 2

[0057] In vivo anti-angiogenic activity of peptides analyzed in chicken chorioallantoic membrane (CAM)

[0058] In this study, CAM assay was used to investigate the activity of integrin blocker polypeptides in inhibiting angiogenesis in vivo. Studies have shown that the biosynthesis rate of collagen reaches the maximum from the 8th day to the 11th day of chicken embryo development, which is the most vigorous stage of angiogenesis, and the body's immune system has not yet been fully established, so it is selected to develop to the 8th day The chick embryos began to be administered. Considering that the polypeptide on the drug-loaded paper sheet will have a certain diffusion range limitation on the allantoic membrane of chicken embryos, only the number of new blood vessels within a radius of 5 mm from the edge of the paper sheet was counted in the test. Take the following steps:

[0059] (1) Cultivate the Bailaihang chicken embryos on the 6th day in a 37° C. incubator with a h...

Embodiment 3

[0064] Effects of Integrin Blocker Peptide on Corneal Neovascularization in Mice

[0065] (1) Preparation of corneal neovascularization model induced by alkali burn in BALB / c mice:

[0066] Twenty healthy BALB / c mice, male, weighing 20-25 g, were examined under a slit-lamp microscope for the anterior segment and appendages of both eyes to exclude eye lesions. 0.3% ofloxacin eye drops were instilled 1 day before the preparation of the alkali burn model, twice a day. After mice were anesthetized by intraperitoneal injection of 1.8% Avertin, a single-layer filter paper sheet with a diameter of 2 mm was clamped with tweezers, immersed in 1mol / L sodium hydroxide solution to make it saturated, excess liquid was removed, and the filter paper sheet was placed in BALB / c mouse corneal central 40S, discard the filter paper, and immediately rinse the burn area and conjunctival sac with 15ml of PBS for 1min. Wipe off excess water with a cotton swab, and rotate the corneal spatula paralle...

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Abstract

The invention relates to the medical field, in particular to an integrin blocker with integrin affinity and combining capacity. The integrin blocker comprises three polypeptides which can be used for preventing and treating ocular neovascular diseases. The polypeptides of the integrin blocker particularly contain polypeptide I: Ile-Val-Arg-Arg-Ala-Asp-Arg-Ala-Ala-Val-Pro-Gly-Gly-Gly-Gly-Arg-Gly-Asp, polypeptide II: Ala-Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys-Gly-Gly-Gly-Gly-Ile-Val-Arg-Arg-Ala-Asp-Arg-Ala-Ala-Val-Pro, and polyethylene glycol modified polypeptide III: mPEG-SC20k-Ile-Val-Arg-Arg-Ala-Asp-Arg-Ala-Ala-Val-Pro-Gly-Gly-Gly-Gly-Arg-Gly-Asp. The integrin blocker can be used for treating ocular neovascular diseases including corneal ocular neovascular diseases, iridal ocular neovascular diseases, choroidal ocular neovascular diseases, retinal ocular neovascular diseases and the like.

Description

technical field [0001] The invention relates to the field of medicine, in particular to an integrin blocker polypeptide for preventing and treating neovascular eye diseases. Background technique [0002] Neovascularization, under normal physiological conditions, is highly regulated and is an essential process in reproduction, embryonic development, tissue repair and wound healing. [0003] Angiogenesis occurs in response to a variety of pro-angiogenic stimuli such as growth factors, cytokines and other physiological molecules, as well as other factors such as hypoxia and low pH. The angiogenic cascade of neovascular development requires the cooperation of multiple molecules that regulate essential cellular processes such as extracellular matrix (ECM) remodeling, invasion, migration, proliferation, differentiation, and tubule formation, among others. Provascular molecules such as VEGF, PDGF and others activate endothelial cells by stimulating their cell surface receptors. T...

Claims

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Application Information

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IPC IPC(8): A61P27/02A61P9/10A61K38/10A61K38/16A61P27/06
CPCY02A50/30
Inventor 徐寒梅李永兵
Owner CHINA PHARM UNIV
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