Method of inducing angiogenesis

Details Method of inducing angiogenesis Method of inducing angiogenesis

1999-11-08

2001-12-11

Nguyen, Dave T. (Department: 1632)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

C514S002600, C435S320100, C435S455000, C435S456000, C530S350000, C530S399000

Reexamination Certificate

active

06329348

ABSTRACT:

TECHNICAL FIELD OF THE INVENTION
The present invention relates to a method for enhancing the level of perfusion of blood to a target tissue, a method for treating a target tissue suffering from or at risk of suffering from ischemic damage, and a method of inducing angiogenesis in a target tissue.
BACKGROUND OF THE INVENTION
Angiogenesis, the growth of new blood vessels, is a complex process involving the disruption of vascular basement membranes, migration and proliferation of endothelial cells, and subsequent blood vessel formation and maturation. Several mediators are known to elicit angiogenic responses, and administration of these mediators promotes revascularization of ischemic tissues. Vascular endothelial growth factor (VEGF protein) is one of the most specific of the known angiogenic mediators due to localization of its receptors almost exclusively on endothelial cells. Receptors for VEGF are upregulated under ischemic conditions, and the administration of recombinant VEGF augments the development of collateral vessels and improves function in peripheral and myocardial ischemic tissue.
The delivery of VEGF protein remains a significant challenge. The half-life of VEGF protein is very short; the administration of high doses of VEGF protein is associated with hypotension, and systemic administration of VEGF protein can cause promiscuous induction of angiogenesis in tissues other than that which has been targeted. Promiscuous induction of angiogenesis can cause blindness, increase the aggressiveness of tumor cells, and lead to a multitude of other negative side-effects. Furthermore, the quantity of VEGF protein delivered is important. If too little VEGF protein is delivered, angiogenesis will not be induced, and a significant therapeutic benefit will not be achieved. If too much VEGF protein is delivered, the formation of disorganized vasculature beds, loss of function in the affected tissue, and promiscuous angiogenesis can result.
Attempts to address these problems have utilized methods wherein multiple applications of an angiogenic mediator were made to a target tissue. For example, International Patent Application WO 98/32859 discloses methods of inducing angiogenesis comprising multiple applications of a pharmaceutical composition comprising (a) a pharmaceutically acceptable carrier and (b) an adenoviral vector comprising a DNA encoding an angiogenic peptide, such that the level of perfusion of blood to the target tissue is enhanced.
There remains a need, however, for improved methods of inducing angiogenesis in a target tissue. The present invention provides such a method. These and other advantages of the present invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.
BRIEF SUMMARY OF THE INVENTION
The present invention provides a method for enhancing the level of perfusion of blood to a target location in a host. The method comprises establishing a gradient of an angiogenic mediator of increasing concentration from a source location in the host to a target location in the host, such that the level of perfusion of blood to the target location in the host is enhanced.


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