Biocompatible viscoelastic gel slurries, their preparation and use

• US 5,246,698 A
• Filed: 12/20/1991
• Issued: 09/21/1993
• Est. Priority Date: 07/09/1990
• Status: Expired due to Term

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Biomatrix, Inc. (Sanofi )
• Inventors: Leshchiner, Adelya, Larsen, Nancy E., Leshchiner, Edward, Balazs, Endre A.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): KISHORE, GOLLAMUDI S
• Application Number:
  US07/811,139
• Time in Patent Office: 641 Days
• Field of Search: 252/315.01, 252/315.1, 252/315.3, 424/78.08, 424/78.02-78.04, 424/78.06, 424/78.14, 424/426, 424/428, 424/78.24, 424/78.31, 516/54, 516/944, 530/813, 530/402, 530/411, 524/27, 536/55.1-55.3
• US Class Current: 424/78.08
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/042 Polysaccharides
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: C08L 2666/02 Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: H04B 10/50 Transmitters
• CPC Class Codes: Y10S 530/813 Carrier is a saccharide

Abstract

Disclosed are biocompatible viscoelastic gel slurries formed from a polymeric gel, preferably a hyaluronan or a derivative thereof such as hylan swollen in an aqueous medium and a fluid phase which is an aqueous solution of a polymer which may also but not necessarily be a hyaluronan or derivative thereof. Also disclosed are methods of making such slurries, controlling their rheological properties and the uses thereof.

Claims

1. A method of controlling the rheological and diffusion properties of a biocompatible viscoelastic gel slurry comprising a two phase mixture, a first phase being a particulate biocompatible gel phase, said gel phase comprising a chemically cross-linked glycosaminoglycan, or said glycosaminoglycan chemically co-cross-linked with at least one other polymer selected from the group consisting of polysaccharides and proteins, said gel phase being swollen in a physiologically acceptable aqueous medium and being uniformly distributed in the second phase, said second phase comprising a polymer solution of a water-soluble biocompatible polymer selected from the group consisting of polysaccharides, polyvinylpyrrolidone and polyethylenloxide in said physiologically acceptable aqueous medium, said method comprising changing the polymer concentration in the gel phase by partial removal of the physiologically acceptable aqueous medium from the equilibrated swollen gel before combining said two phases;

said partial removal being effected by subjecting the gel phase to compression, such that there results a 1.05 to 1000 fold increase in the polymer concentration in the gel phase.

2. A method according to claim 1 wherein the increase in the polymer concentration is 1.1 to 500 fold.

3. A method according to claim 2 wherein the increase is 1.2 to 100 fold.