Polyacid/polyalkylene oxide foams and gels and methods for their delivery

• US 6,566,345 B2
• Filed: 04/26/2001
• Issued: 05/20/2003
• Est. Priority Date: 04/28/2000
• Status: Expired due to Term

• Current Assignee: Fziomed, Inc.
• Original Assignee: Fziomed, Inc.
• Inventors: Schwartz, Herbert E., Miller, Mark E., Oppelt, William G., Cortese, Stephanie M.
• Primary Examiner(s): PRYOR, ALTON NATHANIEL
• Application Number:
  US09/843,194
• Publication Number:
  US 20020028181A1
• Time in Patent Office: 754 Days
• Field of Search: 514/54, 514/55, 514/58, 514/57, 424/78.18, 424/78.3
• US Class Current: 514/54
• 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 31/717 Celluloses
• CPC Class Codes: A61K 31/721 Dextrans
• CPC Class Codes: A61K 31/722 Chitin, chitosan
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 31/74 Synthetic polymeric materials
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• 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 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/122 Foams; Dry foams edible foams A61K9/0056
• 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 15/225 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 15/44 Medicaments
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• CPC Class Codes: A61L 2300/418 Agents promoting blood coagulation, blood-clotting agents, embolising agents
• CPC Class Codes: A61L 2400/04 Materials for stopping bleeding
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08L 1/28 Alkyl 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 2666/04 : Macromolecular compounds according to groups C08L7/00 - C08L49/00, or C08L55/00 - C08L57/00; Derivatives thereof
• CPC Class Codes: C08L 2666/18 : Polyesters or polycarbonates according to C08L67/00 - C08L69/00; Derivatives thereof
• CPC Class Codes: C08L 2666/20 : Macromolecular compounds having nitrogen in the main chain according to C08L75/00 - C08L79/00; Derivatives thereof
• CPC Class Codes: C08L 2666/22 : Macromolecular compounds not provided for in C08L2666/16 - C08L2666/20
• 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 67/00 : Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain of polyester-amides C08L77/12; of polyester-imides C08L79/08; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 71/02 : Polyalkylene oxides
• CPC Class Codes: C08L 77/00 : Compositions of polyamides obtained by reactions forming a carboxylic amide link in the main chain of polyhydrazides C08L79/06; of polyamideimides or polyamide acids C08L79/08; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 85/00 : Compositions of macromolecular compounds obtained by reactions forming a linkage in the main chain of the macromolecule containing atoms other than silicon, sulfur, nitrogen, oxygen and carbon; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 85/02 : containing phosphorus

Abstract

The present invention relates to improved methods for delivering bioadhesive, bioresorbable, anti-adhesion compositions. Antiadhesion compositions can be made of intermacromolecular complexes of carboxyl-containing polysaccharides, polyethers, polyacids, polyalkylene oxides, multivalent cations and/or polycations. The polymers are associated with each other, and are then used as fluids, gels or foams. By providing a product bag, the compositions can be delivered as gels or as sprays. By dissolving propellant gases in the compositions, the materials can be delivered as foams, which have decreased density, and therefore can adhere to surfaces that previously have been difficult to coat with antiadhesion gels. Delivery systems can also provide mechanisms for expelling more product, and for directing the flow of materials leaving the delivery system. Bioresorbable, bioadhesive, anti-adhesion, and/or hemostatic compositions are useful in surgery to prevent the formation and reformation of post-surgical adhesions. The biological and physical properties of such compositions 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 selecting the solids content of the composition. 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 antiadhesion material comprising:

an antiadhesion composition comprising a polyacid and a polyalkylene oxide; and

a foaming gas, said material being a foam.

2. The antiadhesion foam of claim 1, wherein the foaming gas is CO₂.

3. The antiadhesion foam of claim 1, wherein the foaming gas is N₂.

4. The antiadhesion foam of claim 1, wherein the polyacid is carboxymethyl cellulose and the polyalkylene oxide is polyethylene oxide.

5. The antiadhesion foam of claim 1, wherein the density of said foam is in the range of about 0.001 to about 1 times the density of the un-foamed antiadhesion composition.

6. The antiadhesion foam of claim 1, wherein said foam has a cell size of between about 0.001″

to about 1.0″

.

7. The antiadhesion foam of claim 1, further comprising a drug.

8. The antiadhesion foam of claim 1, further comprising a hemostatic agent.

9. The antiadhesion foam of claim 1, further comprising a multivalent cation.

10. The antiadhesion foam of claim 9, wherein said multivalent cation is selected from the group consisting of calcium, aluminum, and iron.

11. The antiadhesion foam of claim 9 having a pH of below about 7.5.

12. The antiadhesion foam of claim 9 having a pH below about 6.0.

13. The antiadhesion foam of claim 9 having a pH below about 5.0.

14. The antiadhesion foam of claim 9 having a pH below about 4.0.

15. The antiadhesion foam of claim 9 having a pH below about 3.0.

16. A product comprising:

an antiadhesion material comprising an antiadhesion composition comprising a polyacid and a polyalkylene oxide; and

a foaming gas, said material being a foam;

a canister containing said foam;

a valve adapted to permit flow of said foam therethrough; and

a pressure source.