Biomaterials modified with superoxide dismutase mimics

• US 7,445,641 B1
• Filed: 05/26/2000
• Issued: 11/04/2008
• Est. Priority Date: 05/27/1999
• Status: Expired due to Fees

• Current Assignee: Pharmacia Corporation (Pfizer Inc.)
• Original Assignee: Pharmacia Corporation (Pfizer Inc.)
• Inventors: Brethauer, Kerry, Udipi, Kishore, Thurmond, Bruce, Riley, Dennis, Forster, Denis, Henke, Susan, Ornberg, Richard
• Primary Examiner(s): Isabella; David J
• Application Number:
  US09/580,007
• Time in Patent Office: 3,084 Days
• Field of Search: 514/185, 514/184, 514/492, 514/393, 514/397, 514/6, 514/54, 514/55, 514/57, 623/11.11, 623/13.11, 623/16.11, 623/18.11, 623/23.56, 623/23.57, 623/23.58, 623/23.59, 623/23.6, 623/23.64, 623/23.72, 623/23.75, 623/23.76, 623/66.1, 623/1.1, 623/23.71, 530/400, 536/20, 536/31, 536/58
• US Class Current: 623/23.57
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 31/042 Polysaccharides
• CPC Class Codes: C07F 13/005 Compounds without a metal-carbon linkage
• CPC Class Codes: C07F 15/025 without a metal-carbon linkage
• CPC Class Codes: C08B 15/00 Preparation of other cellulose derivatives or modified cellulose , e.g. complexes
• CPC Class Codes: C08B 15/05 Derivatives containing elements other than carbon, hydrogen, oxygen, halogens or sulfur esters or phosphorous acids C08B5/00
• 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: C08B 37/003 Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
• CPC Class Codes: C08B 37/0072 Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
• CPC Class Codes: C08G 18/10 Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step
• CPC Class Codes: C08G 18/3228 acyclic
• CPC Class Codes: C08G 18/4854 Polyethers containing oxyalkylene groups having four carbon atoms in the alkylene group
• CPC Class Codes: C08G 18/6685 with compounds of group C08G18/3225 or polyamines of C08G18/38
• CPC Class Codes: C08G 18/718 containing silicon
• CPC Class Codes: C08G 18/73 acyclic
• CPC Class Codes: C08H 1/06 derived from horn, hoofs, hair, skin or leather
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

The present invention relates to biomaterials modified with non-proteinaceous catalysts for the dismutation of superoxide, and processes for making such materials. This modification may be by covalent conjugation, copolymerization, or admixture of the non-proteinaceous catalysts with the biomaterial. The resulting modified biomaterials exhibit a marked decrease in inflammatory response and subsequent degradation when placed in contact with vertebrate biological systems.

Claims

1. A modified biomaterial useful for the dismutation of superoxide comprising biomaterial substantially compatible with a biological system and at least one non-proteinaceous catalyst for the dismutation of superoxide covalently bound to the surface of the biomaterial, wherein the non-proteinaceous catalyst for the dismutation of superoxide comprises a pentaazamacrocycle.

2. A modified biomaterial of claim 1, wherein the non-proteinaceous catalysts consists of manganese(II)dichloro-[(4R,9R,14R,19R)-3,10,13,20,26-pentaazatricyclo[20.3.1.0^4,9.0^14,19]hexacosa 1(26), 22(23), 24(25)-triene].

3. A modified biomaterial of claim 1, wherein the non-proteinaceous catalysts consists of manganese(II)dichloro-[(4R,9R,14R,19R)-3,10,13,20,26-pentaazatricyclo[20.3.1.0^4,9.0^14,19]-24-chloro-hexacosa-1(26), 22(23), 24(25)-triene].

4. A modified biomaterial of claim 1, wherein the non-proteinaceous catalysts consists of manganese(II)dichloro-[(4R,9R,14R,19R)-3,10,13,20,26-pentaazatricyclo[20.3.1.0^4,9.0^14,19]-24-thioethylamine-hexacosa-1(26), 22(23), 24(25)-triene].

9. The modified biomaterial of claim 1, wherein the biomaterial substantially compatible with a biological system is selected from the group consisting of a metal, a ceramic, a polymer, and a composite thereof.

10. The modified biomaterial of claim 9, wherein the biomaterial substantially compatible with a biological system is selected from the group consisting of stainless steel, tantalum, titanium, nitinol, gold, platinum, inconel, iridium, silver, tungsten, nickel, chromium, vanadium, and alloys comprising any of the foregoing metals and alloys.

11. The modified biomaterial of claim 9, wherein the biomaterial substantially compatible with a biological system is selected from the group consisting of a metal, a ceramic, a polymer, and a composite thereof.

12. The modified biomaterial of claim 9, wherein the biomaterial substantially compatible with a biological system is a polymer selected from the group consisting of:

polyurethane, polyureaurethane, polyalkylene glycols, polyethylene teraphthalate, ultra high molecular weight polyethylene, polypropylene, polyesters, polyamides, polycarbonates, polyorthoesters, polyesteramides, polysiloxane, polyolefins, polytetrafluoroethylene, polysulfones, polyanhydrides, polyalkylene oxides, polyvinyl halides, polyvinyledene halides, acrylic, methacrylic, polyacrylonitrile, polyvinyl, polyphosphazene, polyethylene-co-acrylic acid, silicone, block copolymer of any of the foregoing polymers, random copolymers of any of the foregoing polymers, graft copolymers of any of the foregoing polymers, crosslinked polymers of any of the foregoing polymers, hydrogels, and mixtures of any of the foregoing polymers.

5. A modified biomaterial useful for the dismutation of superoxide comprising of biomaterial substantially compatible with a biological system and at least one non-proteinaceous catalyst for the dismutation of superoxide covalently bound to the surface of the biomaterial, wherein the non-proteinaceous catalyst for the dismutation of superoxide comprises a compound of structure:

6. The modified biomaterial of claim 5, wherein the non-proteinaceous catalyst consists of a compound of structure:

7. The modified biomaterial of claim 5, wherein the non-proteinaceous catalyst consists of a compound of structure:

8. The modified biomaterial of claim 5, wherein the non-proteinaceous catalyst consists of a compound of structure:

13. The modified biomaterial of claim 5, wherein the biomaterial substantially compatible with a biological system is selected from the group consisting of a metal, a ceramic, a polymer, and a composite thereof.

14. The modified biomaterial of claim 13, wherein the biomaterial substantially compatible with a biological system is a metal selected from the group consisting of stainless steel, tantalum, titanium, nitinol, gold, platinum, inconel, iridium, silver, tungsten, nickel, chromium, vanadium, and alloys comprising any of the foregoing metals and alloys.

15. The modified biomaterial of claim 13, wherein the biomaterial substantially compatible with a biological system is selected from the group consisting of a metal, a ceramic, a polymer, and a composite thereof.

16. The modified biomaterial of claim 13, wherein the biomaterial substantially compatible with a biological system is a polymer selected from the group consisting of:

polyurethane, polyureaurethane, polyalkylene glycols, polyethylene teraphthalate, ultra high molecular weight polyethylene, polypropylene, polyesters, polyamides, polycarbonates, polyorthoesters, polyesteramides, polysiloxane, polyolefins, polytetrafluoroethylene, polysulfones, polyanhydrides, polyalkylene oxides, polyvinyl halides, polyvinyledene halides, acrylic, methacrylic, polyacrylonitrile, polyvinyl, polyphosphazene, polyethylene-co-acrylic acid, silicone, block copolymer of any of the foregoing polymers, random copolymers of any of the foregoing polymers, graft copolymers of any of the foregoing polymers, crosslinked polymers of any of the foregoing polymers, hydrogels, and mixtures of any of the foregoing polymers.