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Angiogenesis regulating composition and method for regulating angiogenesis

angiogenesis and composition technology, applied in the field of angiogenesis regulating composition and method for regulating angiogenesis, can solve the problems of reducing peripheral vision loss and night vision difficulties, affecting the normal affecting the function of the body, so as to and reduce the risk of angiogenic diseases.

Inactive Publication Date: 2012-05-10
AIR WATER INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0031]The present invention can thus provide a composition effective in treating and preventing angiogenic diseases, that can medically control angiogenic diseases, and medically regulate angiogenesis in ophthalmologic diseases in particular, and allows treatment without inhibiting physiological neovascularization, with a limited side effect and significantly safely, and an angiogenesis regulation method using the same.

Problems solved by technology

Although a laser photocoagulation is generally used as a representative surgical treatment, this treatment is compensatory tissue destruction applied reluctantly in a pathologically advanced stage, which may cause reducing peripheral vision loss and night vision difficulties, and a change of color vision.
While these inhibitors are effective in inhibiting pathologic neovascularization of retinopathy and in diabetic macular edema, it has been reported that the anti-VEGF antibody inhibits physiological neovascularization and causes systemic wound-healing retardation, cerebral hemorrhage, cerebrovascular accidents, myocardial infarction, angina pectoris, and other serious side effects.
Furthermore, because VEGF inhibitor and other similar ophthalmovascular therapeutic agents are administered to a patient through intravitreous injection to alleviate a systemic side effect, this treatment imposes a large burden on the patients, and the intravitreous injection not only injures the patients' ocular tissues but will also constantly expose their lenses and retinal tissues to a risk of bacterial infection.

Method used

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  • Angiogenesis regulating composition and method for regulating angiogenesis
  • Angiogenesis regulating composition and method for regulating angiogenesis
  • Angiogenesis regulating composition and method for regulating angiogenesis

Examples

Experimental program
Comparison scheme
Effect test

exemplary experiment 1

[0057] Evaluation of Effect for Reducing Retinal Avascular Area by Nitrate and Nitrite

[0058]The effect of sodium nitrate and sodium nitrite for reducing retinal avascular area was evaluated by the model mice of oxygen-induced retinal angiogenesis which were generally used for in vivo pathologic neovascularization model in a retinal angiogenic disease.

[0059]Preparation of Test Compound Injection

[0060]Sodium nitrate or sodium nitrite as a test compound was dissolved in physiological saline for injection to prepare a test compound injection of 3-15 μmol / L.

[0061]Experimental Procedure

[0062]C57BL / 6J mouse (SLC) was used as an experimental animal. The model mice of oxygen-induced retinal angiogenesis were provided according to Smith et al. (e.g., Lois E. H. Smith et al., “Oxygen-Induced Retinopathy in the Mouse”, Invest Ophthalmol Vis Sci., Vol. 35, pp. 101-11 1 (1994) (NPL 8)). Neonatal mice were bred from the 7th day (P7) to the 12th day (P12) after birth together with a parent mouse in...

exemplary experiment 3

[0078] Evaluating Effect of Nitrate and Nitrite in Regulating Retinal Angiogenesis

[0079]For the model mice of oxygen-induced retinal angiogenesis, retinal angiogenesis is induced by providing 75% oxygen followed by breeding in room air during P12-P17. Therefore the effect of angiogenesis regulation of the invention was clearly examined by administration of sodium nitrate or sodium nitrite from the beginning of retinal angiogenesis (or from P12).

[0080]Preparation of Test Compound Injection

[0081]Sodium nitrate or sodium nitrite as a test compound was dissolved in physiological saline for injection to prepare a test compound injection of 3 μmol / L.

[0082]Experimental Procedure

[0083]Preparation of the model mice of oxygen-induced retinal angiogenesis, fluorescent imaging of retinal vessels and a retinal flat-mount were operated according to exemplary experiment 1. However sodium nitrate or sodium nitrite was injected to a cervical region hypodermically once per day in amount of 15 μmol / kg...

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Abstract

An angiogenesis regulating composition used to treat / prevent an angiogenic disease in a subject, that contains in an effective amount at least one of nitrate, nitrite, and a compound convertible into nitrate or nitrite after the compound is absorbed into the subject, and an angiogenesis regulation method administering to a subject a composition containing as an active ingredient at least one of nitrate. nitrite, and a compound convertible into nitrate or nitrite after the compound is absorbed into the subject, provide a composition effective in treating and preventing angiogenic diseases, that can medically control angiogenic diseases, and medically regulate angiogenesis in ophthalmologic diseases in particular, and allows treatment without inhibiting physiological neovascularization, with a limited side effect and significantly safely, and an angiogenesis regulation method using the same.

Description

TECHNICAL FIELD[0001]The present invention relates to a composition used to regulate angiogenesis to treat and prevent angiogenic diseases, and a method for regulating angiogenesis.BACKGROUND ART[0002]Angiogenesis refers to formation of a new blood vessel branch by endothelial cell proliferation and migration and remodeling from a pre-existing blood vessel of a tissue. In recent years, the mechanism of angiogenesis has drastically been revealed by cell biological approaches. Angiogenesis is started by induced expression of VEGF (vascular endothelial growth factor) mRNA which occurs by activation of a transcription factor HIF (hypoxia-inducible factor) responding to ischemia-based hypoxia. The produced VEGF binds to a VEGF receptor (VEGFR) localized in a vascular endothelial cell, and activates an intracellular signaling pathway. This results in decomposed extracellular basement membrane, followed stepwise by vascular endothelial cell migration / proliferation, lumen formation of vascu...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K33/00A61P27/02C01B21/20A61P27/06
CPCA61K31/21A61K33/00A61K33/26A61K2300/00A61P9/00A61P27/02A61P27/06
Inventor FUJIMORI, JUNYABABA, HIDEKAZUMURATA, TOSHINORI
Owner AIR WATER INC
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