Anti-thrombogenic PVP-heparin polymer

• US 4,239,664 A
• Filed: 10/31/1978
• Issued: 12/16/1980
• Est. Priority Date: 10/31/1978
• Status: Expired due to Term

• Current Assignee: Research Corporation
• Original Assignee: Research Corporation
• Inventors: Schmer, Gottfried, Teng, Lin-Nar
• Primary Examiner(s): Woodberry, Edward M.
• Application Number:
  US05/956,049
• Time in Patent Office: 777 Days
• Field of Search: 260/9, 260/17.4 R, 424/183
• US Class Current: 525/54.2
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 47/58 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
• CPC Class Codes: A61L 33/0029 using an intermediate layer of polymer
• CPC Class Codes: C08B 37/0075 Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof
• CPC Class Codes: C08G 81/02 at least one of the polymers being obtained by reactions involving only carbon-to-carbon unsaturated bonds
• CPC Class Codes: C08L 39/06 Homopolymers or copolymers of N-vinyl-pyrrolidones

Abstract

The present invention relates to a group of novel compounds defined as covalently bound poly-N-vinyl pyrrolidinone (PVP)-heparins. These compounds are synthesized on the basis of a novel concept that heparin molecules can be modified to have new desirable qualities by binding heparin covalently to an appropriate polymer carrier which has the desired characteristics.

Heparin is hydrophilic and thereby insoluble in organic solvent. It has a short half-life in vivo. PVP-heparins, on the other hand, not only retain the anticoagulant activities of heparin, but also have the solubility (in organic solvents) and longer half-life in vivo of PVP.

PVP-heparins are produced either in anhydrous or heterogeneous media wherein PVP is activated by thionyl chloride to produce an imidoyl ion which is subsequently bound to heparin. PVP-heparin produced in anhydrous media is chloroform soluble and has been found useful for coating plastics and similar substances. PVP-heparin produced in heterogeneous media has been found to have twice the half-life in sheep as the native, unmodified heparin.

Claims

1. An anti-thrombogenic chloroform soluble polymer compound where the PVP has a molecular weight of 10,000 to 360,000 and heparin has a normal molecular weight of 6,000 to 20,000 consisting essentially of a covalently bound poly-N-vinyl pyrrolidinone (PVP)-heparin formed by activating PVP with thionyl chloride to form an imidoyl ion and bonding heparin, said polymer compound being useful as a protracted i.v. therapeutic drug in humans.