Reduction of adverse inflammation

• US 20050025804A1
• Filed: 07/19/2004
• Published: 02/03/2005
• Est. Priority Date: 07/28/2003
• Status: Abandoned Application

• Current Assignee: Adam Heller
• Original Assignee: Adam Heller
• Inventors: Heller, Adam
• Application Number:
  US10/894,573
• Publication Number:
  US 20050025804A1
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/41 having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
• CPC Class Codes: A61K 31/555 containing heavy metals, e.g. hemin, hematin, melarsoprol
• CPC Class Codes: A61L 15/18 containing inorganic materials
• CPC Class Codes: A61L 15/44 Medicaments
• CPC Class Codes: A61L 2300/102 Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
• CPC Class Codes: A61L 2300/224 containing metals, e.g. porphyrins, vitamin B12
• CPC Class Codes: A61L 2300/254 Enzymes, proenzymes
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 27/047 Other specific metals or alloys not covered by A61L27/042 - A61L27/045 or A61L27/06
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/022 Metals or alloys
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 39/06 : Free radical scavengers or antioxidants
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Reduction of the likelihood of adverse inflammatory reaction to an implant or a transplant is achieved through several mechanisms including the catalysis of isomerization of peroxynitrite by a hydrogel-bound peroxynitrite isomerization catalysts. A second mechanism controls acceptable and unacceptable dimensions of surface features of implants, such as vascular stents. A third mechanism fabricates implants from materials which are substantially free from alloys transition metals which produce ions of which catalyze cell killing radical formation.

Claims

1. An implant or transplant which has been fabricated or modified to promote the isomerization of peroxynitrite anion to nitrate anion.

2. An implant or transplant as in claim 1, wherein at least a portion of a surface is coated with a catalyst which promotes said isomerization.

3. An implant or transplant as in claim 2, wherein said catalyst is a protein, an enzyme and/or contains a metal complex.

4. An implant as in claim 3, wherein the catalyst is a permeable hydrogel containing a porphyrin and/or phthalocyanine of a transition metal.

5. An implant as in claim 4, wherein the transition metal comprises iron and/or manganese.

6. A method for inhibiting inflammation associated with implantation or transplantation in a patient, said method comprising:

coating at least a portion of an implant device or transplantation structure with a material which catalyzes the isomerization of peroxynitrite anion to nitrate anion.

7. A method as in claim 6, wherein said material comprises a catalyst which promotes said isomerization.

8. A method as in claim 7, wherein said catalyst is a protein, an enzyme and/or contains a metal complex.

9. A method as in claim 8, wherein the catalyst is a permeable hydrogel containing a porphyrin and/or phthalocyanine of a transition metal.

10. A method as in claim 9, wherein the transition metal comprises iron and/or manganese.

11. A hydrogel for coating a medical implant or transplant, said hydrogel comprising a catalyst which promotes the isomerization of peroxynitrite anion to nitrate anion.

12. A hydrogel as in claim 11, wherein said catalyst is a protein, an enzyme and/or contains a metal complex.

13. A hydrogel as in claim 12, wherein the catalyst is a permeable hydrogel containing a porphyrin and/or phthalocyanine of a transition metal.

14. A hydrogel as in claim 13, wherein the transition metal comprises iron and/or manganese.

15. A hydrogel as in claim 14, comprising a co-polymer of acrylamide.

16. A medical implant having an exterior surface, said exterior surface having features with dimensions which are in a size range characteristic of pathogenic bacteria present at a surface density below a threshold value which promotes phagocytosis.

17. An implant as in claim 16, wherein the feature size range is from 0.1 μ

m to 100 μ

m.

18. An implant as in claim 17, wherein the threshold surface density is 1000 features per mm².

19. A method for fabricating a medical implant, said method comprising fabricating, treating, or coating at least an exterior surface of the implant so that said surface has features with dimensions which are in a size range characteristic of phagocytosis bacteria present at a surface density below a threshold value which promotes phagocytosis.

20. A method as in claim 19, wherein the feature size range is from 0.1 μ

m to 100 μ

m.

21. A method as in claim 20, wherein the threshold surface density is 1000 features per mm².

22. A medical implant having a surface which is substantially free from transition metals which form dissolved ions which catalyze the formation of cell killing radicals.

23. A medical implant as in claim 22, wherein said transition metals are present at or near the surface at an atomic percent below 1%.

24. A medical implant as in claim 23, wherein said transition metals include cooper, iron, cobalt, and nickel.

25. A medical implant as in claim 24, wherein said surface is at least partly composed of a metal selected from the group consisting of yttrium, zirconium, hafnium, magnesium, calcium, aluminum, lithium, and scandium or any of their alloys, or their oxides.

26. A medical implant as in any of claims 22 to 25, wherein the implant is composed of a metal or alloy having a 20% or great elongation failure at room temperature.

27. A medical implant as in claim 22, wherein the implant is a stent composed of at least 95 atomic percent zirconium with from 0 to 5 atomic percent hafnium.

28. A method for fabricating a medical implant, said method comprising forming at least a surface portion of the implant from a material which is substantially free from transition metals which form dissolved ions which catalyze the formation of cell killing radicals.

29. A method as in claim 28, wherein said transition metals are present at or near the surface at an atomic percent below 1%.

30. A method as in claim 29, wherein said transition metals include cooper, iron, cobalt, and nickel.

31. A method as in claim 30, wherein said surface is at least partly composed of a metal selected from the group consisting of yttrium, zirconium, hafnium, magnesium, calcium, aluminum, lithium, and scandium or any of their alloys, or their oxides.

32. A method as in any of claims 28 to 31, wherein the implant is composed of a metal or alloy having a 20% or great elongation failure at room temperature.

33. A method as in claim 28, wherein the implant is a stent composed of at least 95 atomic percent zirconium with from 0 to 5 atomic percent hafnium.