Anti-angiogenic compositions and methods of use

Inactive Publication Date: 2006-02-16
ANGIOTECH PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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

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 surprisingl

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Preparation of Anti-Invasive Factor

[0220] The shoulder girdle and skull from a dogfish is excised, then scraped with a scalpel in order to remove all muscle and associated connective tissue from the cartilage. The cartilage is then homogenized with a tissue grinder, and extracted by continuous stirring at room temperature for 2 to 5 days in a solution containing 2.0 M guanidium hydrochloride and 0.02 M MES at pH 6.0.

[0221] After 2 to 5 days, the cartilage extract is passed through gauze netting in order to remove the larger constituents. The filtrate is then passed through an Amicon ultrafiltration unit which utilizes spiral-wound cartridges, with a molecular weight cutoff of 100,000. The filtrate (containing proteins with a molecular weight of less than 100,000 daltons) is then dialyzed against 0.02 M MES buffer (pH 6) with an Amicon ultrafiltration unit which retains proteins with a molecular weight of greater than 3,000 daltons. Utilizing this method, low molecular weight prote...

example 2

Analysis of Various Agents for Anti-Angiogenic Activity

[0222] A. Chick Chorioallantoic Membrane (“Cam”) Assays

[0223] Fertilized, domestic chick embryos were incubated for 3 days prior to shell-less culturing. In this procedure, the egg contents were emptied by removing the shell located around the air space. The interior shell membrane was then severed and the opposite end of the shell was perforated to allow the contents of the egg to gently slide out from the blunted end. The egg contents were emptied into round-bottom sterilized glass bowls and covered with petri dish covers. These were then placed into an incubator at 90% relative humidity and 3% CO2 and incubated for 3 days.

[0224] Paclitaxel (Sigma, St. Louis, Mich.) was mixed at concentrations of 1, 5, 10, 30 μg per 10 ml aliquot of 0.5% aqueous methylcellulose. Since paclitaxel is insoluble in water, glass beads were used to produce fine particles. Ten microliter aliquots of this solution were dried on parafilm for 1 hour ...

example 3

Encapsulation of Suramin

[0237] One milliliter of 5% ELVAX (poly(ethylene-vinyl acetate) cross-linked with 5% vinyl acetate) in dichloromethane (“DCM”) is mixed with a fixed weight of sub-micron ground sodium suramin. This mixture is injected into 5 ml of 5% Polyvinyl Alcohol (“PVA”) in water in a 30 ml flat bottomed test tube. Tubes containing different weights of the drug are then suspended in a multi-sample water bath at 40° for 90 minutes with automated stirring. The mixtures are removed, and microsphere samples taken for size analysis. Tubes are centrifuged at 1000 g for 5 min. The PVA supernatant is removed and saved for analysis (nonencapsulated drug). The microspheres are then washed (vortexed) in 5 ml of water and recentrifuged. The 5 ml wash is saved for analysis (surface bound drug). Microspheres are then wetted in 50 ul of methanol, and vortexed in 1 ml of DCM to dissolve the ELVAX. The microspheres are then warmed to 40° C., and 5 ml of 50° C. water is slowly added with...

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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 biliary, 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. ...

Claims

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Application Information

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IPC IPC(8): A61K38/54A61K31/203A61K31/337A61K9/16A61K9/51A61K9/70A61K31/122A61K31/136A61K31/185A61K31/335A61K31/519A61K31/57A61K33/24A61K38/00A61K38/57A61K45/06A61K47/48A61L31/10A61L31/14A61L31/16C07K14/81C08L23/08C08L67/04
CPCA61K45/06Y10S514/825C08L2312/00C08L2203/02C08L67/04C08L23/0853C08L23/0815C07K14/811A61L2300/622A61L2300/606A61K9/0019A61K9/1635A61K9/1647A61K9/1658A61K9/167A61K9/5153A61K9/7007A61K31/122A61K31/136A61K31/185A61K31/203A61K31/335A61K31/337A61K31/519A61K31/57A61K33/24Y10S514/826A61K47/32A61K47/34A61K47/48A61K47/48869A61L31/10A61L31/145A61L31/16A61L2300/416A61K2300/00C08L23/08C08L2666/18C08L2666/06A61L2430/36A61K47/50A61K47/6925
Inventor HUNTER, WILLIAMMACHAN, LINDSAYARSENAULT, A.
Owner ANGIOTECH PHARMA INC
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