Anti-angiogenic compositions and methods of use

Abstract

The present invention provides compositions comprising an anti-angiogenic factor, and a polymeric carrier. Representative examples of anti-angiogenic factors include Anti-Invasive Factor, Retinoic acids and derivatives thereof, and taxol. Also provided are methods for embolizing blood vessels, and eliminating biliamy, urethral, esophageal, and tracheal / bronchial obstructions.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of co-pending PCT application CA94 / 00373, filed Jul. 19, 1994. In addition, this application is a continuation-in-part of pending U.S. patent application Ser. No. 08 / 094,536, filed Jul. 19, 1993. TECHNICAL FIELD [0002] The present invention relates generally to compositions and methods for treating cancer and other angiogenic-dependent diseases, and more specifically, to compositions comprising anti-angiogenic factors and polymeric carriers, stents which have been coated with such compositions, as well as method for utilizing these stents and compositions. BACKGROUND OF THE INVENTION [0003] Angiogenesis-dependent diseases (i.e., those diseases which require or induce vascular growth) represent a significant portion of all diseases for which medical treatment is sought. For example, cancer is the second leading cause of death in the United States, and accounts for over one-fifth of the total mortality....

AI Technical Summary

Benefits of technology

[0020] Within another aspect of the present invention, methods are provided for inhibiting angiogenesis in patients with non-tumorigenic, angiogenesis-dependent diseases, comprising administering to a patient a therapeutically effective amount of paclitaxel to a patient with a non-tumorigenic angiogenesis-dependent disease, such that the formation of new blood vessels is inhibited. Within other aspects, methods are provided for embolizing blood vessels in non-tumorigenic, angiogenesis-dependent diseases, comprising delivering to the vessel a therapeutically effective amount of a composition comprising paclitaxel, such that the blood vessel is effectively occluded.

Problems solved by technology

One difficulty with this approach, however, is that radiotherapeutic and chemotherapeutic agents are toxic to normal tissues, and often create life-threatening side effects.

In addition, these approaches often have extremely high failure / remission rates.

Such agents have generally been useful as adjuvants and as nonspecific stimulants in animal tumor models, but have not as of yet proved to be generally effective in humans.

However, one difficulty is that most monoclonal antibodies are of murine origin, and thus hypersensitivity against the murine antibody may limit its efficacy, particularly after repeated therapies.

One additional difficulty of present methods is that local recurrence and local disease control remains a major challenge in the treatment of malignancy.

Unfortunately, 202,000 (or 32% of all patients with localized disease) will relapse after the initial treatment.

Unfortunately, 39% of those treated with lumpectomy alone will develop a recurrence of the disease, and surprisingly, so will 25% of those in which the resection margin is found to be clear of tumor histologically.

However, despite evidence that such treatments can transiently decrease the size of the hepatic lesions (e.g., systemic chemotherapy and, hepatic arterial chemotherapy initially reduces lesions in 15-20%, and 80% of patients, respectively), the lesions invariably reoccur.

One method that has been attempted for the treatment of tumors with limited success is therapeutic embolization.

A related problem to tumor formation is the development of cancerous blockages which inhibit the flow of material through body passageways, such as the bile ducts, trachea, esophagus, vasculature and urethra.

The major problem with stents, however, is that they do not prevent the ingrowth of tumor or inflammatory material through the interstices of the stent.

If this material reaches the inside of a stent and compromises the stent lumen, it may result in blockage of the body passageway into which it has been inserted.

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