Biodegradable in situ forming film dressing

• US 5,792,469 A
• Filed: 06/07/1995
• Issued: 08/11/1998
• Est. Priority Date: 03/12/1992
• Status: Expired due to Term

• Current Assignee: Tolmar Therapeutics, Inc. (TOLMAR Holding, Inc.)
• Original Assignee: Atrix Laboratories, Inc. (TOLMAR Holding, Inc.)
• Inventors: Dunn, Richard L., Tipton, Arthur J., Fujita, Shawn M.
• Primary Examiner(s): Bawa, Raj
• Application Number:
  US08/482,851
• Time in Patent Office: 1,161 Days
• Field of Search: 424/78.06, 424/45, 424/422, 424/426, 523/113, 604/218
• US Class Current: 424/422
• CPC Class Codes: A61K 9/7015 Drug-containing film-forming compositions, e.g. spray-on
• CPC Class Codes: A61L 15/44 Medicaments
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 24/0042 Materials resorbable by the body
• CPC Class Codes: A61L 26/00 Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
• CPC Class Codes: A61L 26/0066 Medicaments; Biocides
• CPC Class Codes: A61L 26/0076 Sprayable compositions
• CPC Class Codes: A61L 26/0085 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 26/009 Materials resorbable by the body

Abstract

The invention is directed to a biodegradable film dressing with or without additional therapeutic agents, an apparatus for spray delivery and a method for formation of the film dressing-on a human or animal tissue. The film dressing is formed from a liquid composition of at least one biodegradable/bioerodible thermoplastic polymer in a pharmaceutically acceptable solvent. The spray apparatus includes a vessel containing the liquid composition with a dispensing means. The film is formed by dispensing, preferably by spraying, the liquid composition onto a tissue site and contacting the liquid composition with an aqueous based fluid to coagulate or solidify the film onto the human or animal tissue. The biodegradable film can be used to protect and to promote healing of injured tissue and/or to deliver biologically active agents.

Claims

1. A liquid composition suitable for forming an in situ biodegradable film dressing on a human or animal tissue, comprising:

a liquid formulation of a biodegradable thermoplastic polymer that is insoluble in aqueous or body fluids and an organic solvent that is soluble in aqueous or body fluids;

wherein the composition comprises about 0.01-2 g polymer per ml solvent, and has a viscosity of about 0.1-2000 cps which effectively allows for aerosolization, and wherein the amount and molecular weight of said polymer is such that the composition is capable of coagulating or solidifying to form a film dressing upon contact with an aqueous or based fluid.

2. The composition of claim 1, wherein the solvent is a liquid aerosol propellant.

3. The composition of claim 2, wherein the aerosol propellant is a liquid selected from the group consisting of trichloromonofluoromethane, dichlorodifluoromethane, dichloromonofluoromethane, 2-tetrafluoroethane, 1,1-dichloro-1,2,2-tetrafluoroethane, 1-chloro-1,1-difluoroethane, 1,1-difluoroethane, octofluorocyclobutane, propane, isobutane, N-butane, and mixtures thereof.

4. The composition according to claim 1, wherein the biodegradable thermoplastic polymer is selected from the group consisting of polylactides, polyglycolides, polycaprolactones, polyethylene glycols, polyanhydrides, polyamides, polyurethanes, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates, polyalkylene succinates, poly(amino acids), poly(methyl vinyl ether), and copolymers, terpolymers, and combinations thereof.

5. The composition according to claim 1, wherein the organic solvent is selected from the group consisting of N-methyl-2-pyrrolidone, 2-pyrrolidone, acetone, acetic acid, ethyl acetate, ethyl lactate, methyl acetate, methyl ethyl ketone, dimethylforamide, dimethyl sulfoxide, dimethyl sulfone, tetrahydrofuran, caprolactam, decylmethysulfoxide, oleic acid, propylene carbonate, N,N-diethyl-m-toluamide, and 1-dodecylazacycloheptan-2-one, and combinations thereof.

6. The composition of claim 1, wherein the film is a flexible, mechanical and microbial barrier dressing on the tissue.

7. The composition of claim 1, further comprising an agent selected from the group consisting of a biologically-active agent, plasticizer, pore-forming agent, colorant, and combinations thereof.

8. The composition of claim 1, further comprising a biologically-active agent and a modifying agent to alter release of the biologically-active agent from the film dressing.

9. The composition of claim 1, comprising a biologically-active agent and an agent to alter percutaneous absorption of the biologically-active agent.

10. The composition of claim 8, wherein the modifying agent is selected from the group consisting of phthalic esters, benzylphthalates, glycol benzoates, trimellitates, adipates, azelates, sebacates, esters of aliphatic and aromatic di- and tricarboxylic acids, organic phosphates, sesame oil, soybean oil, and combinations thereof.

11. The composition of claim 9, wherein the absorption altering agent is selected from the group consisting of propylene glycol, glycerol, urea, diethyl sebecate sodium, lauryl sulfate, sodium lauryl sulfate, sorbitan ethoxylates, oleic acid, pyrrolidone carboxylate esters, N-methylpyrrolidone, N,N-diethyl-m-tolumide, dimethyl sulfoxide, alkyl methyl sulfoxides, and combinations thereof.

12. The composition of claim 7, wherein the agent is a biologically-active agent.