Compositions of polyacids and methods for their use in reducing adhesions

• US 20050074495A1
• Filed: 11/23/2004
• Published: 04/07/2005
• Est. Priority Date: 06/17/1997
• Status: Abandoned Application

• Current Assignee: Fziomed, Inc.
• Original Assignee: Fziomed, Inc.
• Inventors: Schwartz, Herbert E., Oppelt, William G., Cortese, Stephanie M., Blackmore, John M.
• Application Number:
  US10/995,448
• Publication Number:
  US 20050074495A1
• Time in Patent Office: Days
• US Class Current: 424/484
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• 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 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/042 Polysaccharides
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 33/062 Mixtures of macromolecular compounds
• CPC Class Codes: C08B 11/20 Post-etherification treatments of chemical or physical type, e.g. mixed etherification in two steps, including purification
• CPC Class Codes: C08B 15/00 Preparation of other cellulose derivatives or modified cellulose , e.g. complexes
• CPC Class Codes: C08B 37/00 Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof cellulose D21; microbiological processes C12P
• CPC Class Codes: C08L 1/26 Cellulose ethers
• CPC Class Codes: C08L 1/286 substituted with acid radicals, e.g. carboxymethyl cellulose [CMC] C08L1/282 takes precedence
• CPC Class Codes: C08L 2666/02 Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 2666/26 Natural polymers, natural resins or derivatives thereof according to C08L1/00 - C08L5/00, C08L89/00, C08L93/00, C08L97/00 or C08L99/00
• CPC Class Codes: C08L 5/00 Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
• CPC Class Codes: C08L 71/02 Polyalkylene oxides

Abstract

The present invention relates to improved methods for making and using bioadhesive, bioresorbable, anti-adhesion compositions made of inter-macromolecular complexes of carboxyl-containing polysaccharides, polyethers, polyacids, polyalkylene oxides, multivalent cations and/or polycations. The polymers are associated with each other and are then either dried into membranes or sponges or are used as fluids or microspheres. Bioresorbable, bioadhesive, antiadhesion compositions are useful in surgery to prevent the formation and reformation of post-surgical adhesions. The compositions are designed to breakdown in vivo, and thus be removed from the body. Membranes are inserted during surgery either dry or optionally after conditioning in aqueous solutions. The antiadhesion, bioadhesive, bioresorptive, antithrombogenic and physical properties of such membranes and gels can be varied as needed by carefully adjusting the pH and/or cation content of the polymer casting solutions, polyacid composition, the polyalkylene oxide composition, or by conditioning the membranes prior to surgical use. Multi-layered membranes can be made and used to provide further control over the physical and biological properties of antiadhesion membranes. Membranes and gels can be used concurrently. Antiadhesion compositions may also be used to lubricate tissues and/or medical instruments, and/or deliver drugs to the surgical site and release them locally.

Claims

1. An ionically cross-linked gel comprising:

a polyacid (PA);

a polyalkylene oxide (PO); and

a water soluble, monoatomic multivalent cation, wherein said polyacid has a degree of substitution of about 0.3 to about 2.

2. The gel of claim 1, wherein said polyacid has a degree of substitution of about 0.81 to about 1.12.

3. The gel of claim 1, wherein said polyacid has a degree of substitution of about 0.81 to about 1.17.

4. The gel of claim 1, wherein said polyacid has a degree of substitution of about 0.81 to about 1.19.

5. The gel of claim 1, wherein said polyacid has a degree of substitution of about 0.5 to about 1.7.

6. The gel of claim 1, wherein said polyacid has a degree of substitution of about 0.65 to about 1.45.

7. The gel of claim 1, wherein said polyacid has a degree of substitution of about 0.81 to about 0.82.

8. The gel of claim 1, wherein said gel comprises at least two different polyacids.

9. The gel of claim 8, wherein each of said at least two different polyacids has a different degree of substitution from the degrees of substitution of the other polyacids.

10. The gel of claim 1, wherein an average degree of substitution of said polyacids in said gel is determined by the relative proportions of at least two different polyacids, each of said polyacids having a degree of substitution.

11. The gel of claim 8, comprising a first polyacid having a first degree of substitution and a second polyacid having a second degree of substitution.

12. The gel of claim 1, wherein said polyacid is selected from the group consisting of a carboxypolysaccharide, polyacrylic acid, polyamino acid, polylactic acid, polyglycolic acid, polymethacrylic acid, polyterephthalic acid, polyhydroxybutyric acid, polyphosphoric acid, polystyrenesulfonic acid, and copolymers of said polyacids.

13. The gel of claim 1, wherein said polyacid is a carboxypolysaccharide selected from the group consisting of carboxymethyl cellulose (CMC), carboxyethyl cellulose, chitin, carboxymethyl chitin, hyaluronic acid, alginate, propylene glycol alginate, pectin, carboxymethyl dextran, carboxymethyl chitosan, heparin, heparin sulfate, chondroitin sulfate and polyuronic acids.

14. The gel of claim 13, wherein said polyuronic acid is selected from the group consisting of polymannuronic acid, polyglucuronic acid and polyguluronic acid.

15. The gel of claim 1, dried to form a membrane.

16. The gel of claim 1, further comprising a drug.

17. The gel of claim 16, wherein said drug is selected from the group consisting of antibacterial agents, antiinflammatory agents, antiparasitics, antivirals, anesthetics, antifungals, analgesics, diagnostics, antidepressants, decongestants, antiarthritics, antiasthmatics, anticoagulants, anticonvulsants, antidiabetics, antihypertensives, anti-adhesion agents, anticancer agents, gene replacement or modification agents, and tissue replacement drugs.

18. The gel of claim 1, wherein said cation is selected from the group consisting of Ca⁺³, Al⁺³, Fe⁺², Fe⁺³, Cr⁺³, Mg⁺², Zn⁺², Mn⁺².

19. The gel of claim 1, wherein said polyalkylene oxide is selected from the group consisting of polyethylene oxide (PEO), polyethylene glycol, polypropylene oxide (PPO), and PEO/PPO block copolymers.

20. A method for decreasing post surgical adhesions, comprising placing a gel of claim 1 between tissues that would form an adhesion in the absence of said gel.