Polymer compositions comprising antifibrotic agents, and methods of treatment, pharmaceutical compositions, and methods of preparation therefor

US6517824B1 · kind B1 · utility

Assignees

• University of Medicine & Denistry of New Jersey · US
• Rutgers University · US

Inventors

• Joachim B. Kohn · South Plainfield, US
• John E. Kemnitzer · Plainsboro, US
• George J. Poiani · Jamesburg, US
• David J. Riley · New Brunswick, US

Key dates

• Filing date: May 20, 1996
• Grant date: Feb 11, 2003
• Expiry date: May 20, 2016

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C08G81/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A method for treating pulmonary hypertension and other diseases involving a defect in collagen metabolism, by administration of an effective amount of a liposome encapsulated copolymer conjugate antifibrotic composition, is disclosed. The antifibrotic agent is preferably a proline analog, such as cis-4-hydroxy-L-proline (cHyp). Consistent, high loadings (>98%) of the antifibrotic agent are achieved by first forming a dipeptide with L-lysine, after which the dipeptide is copolymerized with the polymer component to form the copolymer conjugate. The polymer is preferably poly(ethylene glycol) having a weight average molecular weight of from about 500 to about 15,000. There is thus provided the efficient delivery and rateable release of the antifibrotic agent to inhibit collagen accumulation and thereby treat the diseases involved. Accordingly, there is a substantial reduction in the quantity of antifibrotic agent necessary, and thus a corresponding reduction in the potential for toxicity that would otherwise result from its prolonged administration.