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Use of sulfated oligosaccharides as inhibitors of cardiovascular disease

A technology of sulfated oligosaccharides, sulfated, applied in the direction of cardiovascular system diseases, medical preparations containing active ingredients, oligosaccharides, etc., can solve the problems of little understanding of the factors of ECM degradation

Inactive Publication Date: 2000-11-01
AUSTRALIEN NAT UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although it has been suggested that heparanase produced by leukocytes infiltrating developing atherosclerotic plaques may cause loss of ECM heparan sulfate, the factors that cause ECM degradation are poorly understood 4

Method used

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  • Use of sulfated oligosaccharides as inhibitors of cardiovascular disease
  • Use of sulfated oligosaccharides as inhibitors of cardiovascular disease
  • Use of sulfated oligosaccharides as inhibitors of cardiovascular disease

Examples

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Embodiment 1

[0037] The preparation of embodiment 1 sulfated oligosaccharide

[0038] Two sources of oligosaccharides can be used for the following sulfation. The first source is oligosaccharides from naturally occurring polysaccharides. Common preparation methods include enzymatic or chemical partial depolymerization of polysaccharides and size fractionation of the resulting oligosaccharides. Examples of polysaccharides from which oligosaccharides are prepared are mannan and phosphomannan exogenous polysaccharides from the yeast Pichia holstii. The second source is fully synthetic oligosaccharides containing hexoses prepared by chemical polymerization of hexose monomers. A method of making these fully synthetic oligosaccharides is disclosed in the previous International Patent Application PCT / AU96 / 00238. This international patent application also describes an exogenous polysaccharide from yeast Pichia holstii with the structure P-6-Man-α-(1→3)-Man-α-(1→3)-Man-α-...

Embodiment 2

[0040] Use of Sulfated Oligosaccharides to Inhibit Hyperplasia of Vascular Smooth Muscle Materials and Methods Sulfated Oligosaccharides

[0041] Mannopentaose phosphate was isolated from exogenous polysaccharides of yeast Pichia holstii and sulfated as disclosed in International Patent Application PCT / AU96 / 00238. Angiogenesis model

[0042] Two approaches can be used to induce vascular proliferation. In the first method, an approximately 1 cm long carotid artery was dissected from male Fisher 344 rats (18-30 weeks old) after anesthesia. Clamp both ends of the 1 cm long arterial segment with padded arterial forceps. Inject a small amount of saponin solution (0.5 mg / ml PBS solution) into the arterial segment with a needle numbered 30, keep it for 2 minutes, and then absorb the solution. Ligate (5 / 0 silk) a 1 cm long arterial segment at each end of the pinhole, remove the arterial clamp, put the artery back, and suture the wound. The next day the rats were divided...

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Abstract

A method for the inhibition of vascular smooth muscle cell hyperplasia in a human or other warm-blooded animal patient in need of such treatment, comprises administration to the patient of an effective amount of at least one sulfated oligosaccharide, wherein the oligosaccharide has the general formula (I): R1-(Rx)n-R2 wherein R1 and R2 and each Rx represents a monosaccharide unit, all of which may be the same or different, adjacent monosaccharide units being linked by 1}2, 1}3, 1}4 and / or 1}6 glycosidic bonds and n is an integer of from 1 to 6.

Description

field of invention [0001] The present invention relates to sulfated oligosaccharides, and more particularly to the use of certain sulfated oligosaccharides as inhibitors of vascular smooth muscle cell proliferation in the treatment of atherosclerosis and restenosis after coronary angioplasty. Background of the invention [0002] The normal arterial wall consists of a luminal surface covered by a monocellular layer of endothelial cells and a subluminal multicellular layer of smooth muscle cells embedded in a complex extracellular matrix (ECM). The main components of the ECM are glycosaminoglycans and heparan sulfate, which is generally believed to inhibit the proliferation of smooth muscle cells 1-3 . Instead, the mechanism of atherogenesis is associated with loss of ECM heparan sulfate, accompanied by smooth muscle cell migration and proliferation 1-3 . Although it has been suggested that heparanase produced by leukocytes infiltrating developing atherosclerotic plaques ma...

Claims

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Application Information

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IPC IPC(8): A61K31/702A61K31/737A61P9/00C07H3/06A61P9/10A61P43/00C08B37/00
CPCA61K31/737A61K31/7024A61P43/00A61P9/00A61P9/10
Inventor W·B·科登D·J·弗朗西斯C·R·帕里施
Owner AUSTRALIEN NAT UNIV