Claims for Patent: 5,509,932

Summary for Patent: 5,509,932

Title:	Fixed tissue medical devices comprising albumin-binding dyes
Abstract:	An implantable medical device is provided which comprises a fixed tissue incorporating an amount of an albumin-binding dye effective to form a coating of endogenous albumin on said device when the device is in contact with a physiological fluid containing albumin. These albumin-binding dyes have been found to significantly reduce calcification when incorporated in tissue heart valves. A method of increasing the albumin-binding ability of an implantable medical device is also provided.
Inventor(s):	Keogh; James R. (Maplewood, MN), Pearson; David A. (Brooklyn Park, MN), Eaton; John W. (Troy, NY)
Assignee:
Application Number:	08/044,846
Patent Claims:	1. An implantable medical device comprising fixed tissue incorporating an amount of an albumin-binding dye effective to form a coating of endogenous albumin on said device when said device is in contact with a physiological fluid containing albumin. 2. The medical device of claim 1 wherein said albumin-binding dye comprises an aromatic albumin-binding dye. 3. The medical device of claim 2 wherein said aromatic albumin-binding dye comprises a diazo dye, a sulfonic acid dye, or the physiologically-acceptable salts thereof. 4. The medical device of claim 3 wherein said aromatic albumin-binding dye is selected from the group consisting of 1-Amino-4((4-((4-chloro-6-((3(or 4)-sulfophenyl)amino)-1,3, 5-triazin-2-yl)amino)-3-sulfophenyl)amino)-9,10-dihydro-9,10-dioxo-2-anthr acenesulfonic acid, 6.6'-(3,3'-Diamethyl (1,1'-biphenyl)-4,4'diyl)bis(azo))bis(4-amino-5-hydroxy-1,3-naphthalene disulfonic acid) tetrasodium salt, 3,3'-(3,3'-Dimethyl(1,1'-biphenyl)-4,4'diyl)bis(-azo))bis(5-amino-4 hydroxy-2,7-naphthalenehydroxy disulfonic acid) tetrasodium salt, 4,4'-(3H-2,1-Benzoxathiol-3-ylidene) bis(2,6-dibromo-3-methylphenol)S,S-dioxide, 4,4'-(3H-2,1-benzoxathiol-3-ylidene)bis(2-bromo-6-methylphenol) S,S-dioxide, 4-(((4-dimethylamino) phenyl)azo)benzene-sulfonic acid sodium salt, 2-(4'-hydroxyazobenzene)benzoic acid, Procion red H-E 3B and mixtures thereof. 5. The medical device of claim 1 wherein said fixed tissue comprises a conjugate comprising said albumin-binding dye and a physiologically-acceptable water-soluble polysaccharide. 6. The medical device of claim 5 wherein said polysaccharide comprises dextran. 7. The medical device of claim 6 wherein said albumin-binding dye comprises an aromatic albumin-binding dye. 8. The medical device of claim 7 wherein said aromatic albumin-binding dye comprises a diazo dye, a sulfonic acid dye, or the physiologically acceptable salts thereof. 9. The medical device of claim 8 wherein said aromatic albumin-binding dye is selected from the group consisting of 1-Amino-4((4-((4-chloro-6-((3(or 4)-sulfophenyl)amino)-1,3,5-triazin-2-yl)amino)-3-sulfophenyl)amino)-9,10- dihydro-9,10-dioxo-2-anthracenesulfonic acid, 6,6'-(3,3'-Diamethyl (1,1'-biphenyl)-4,4'diyl)bis(azo))bis(4-amino-5-hydroxy-1,3-naphthalene disulfonic acid) tetrasodium salt, 3,3'-(3,3'-Dimethyl(1,1'-biphenyl)-4,4'diyl)bis(azo))bis(5-amino4 hydroxy-2,7-naphthalene disulfonic acid) tetrasodium salt, 4,4'-(3H-2,1-Benzoxathiol-3-ylidene)bis(2,6-dibromo-3-methylphenol)S,S-dio xide, 4,4'-(3H-2,1-benzoaxathiol-3-ylidene)bis(2-bromo-6-methylphenol) S,S-dioxide, 4-(((4-dimethylamino phenyl)azo)benzene-sulfonic acid sodium salt, 2-(4'-hydroxyazobenzene)benzoic acid, Procion red H-E 3B, and mixtures thereof. 10. The medical device of claim 1 wherein said fixed tissue comprises an animal tissue fixed with glutaraldehyde. 11. The medical device of claim 1 wherein said fixed tissue is treated with a reducing agent. 12. The medical device of claim 11 wherein said reducing agent is cyanoborohydride. 13. The medical device of claim 1 wherein the endogenous albumin is human serum albumin. 14. The medical device of claim 1 wherein said medical device is a replacement heart valve and wherein said fixed tissue is the fixed tissue of the replacement heart valve. 15. The medical device of claim 1 wherein said medical device is a replacement blood vessel and said fixed tissue is the fixed tissue of the replacement blood vessel. 16. An implantable medical device comprising: a surface of fixed tissue and on the fixed tissue surface an amount of a conjugate comprising: a. an albumin-binding dye and b. a physiologically-acceptable water-soluble polymer, wherein said amount of the conjugate is effective to bind albumin to the fixed tissue surface of said medical device. 17. The medical device of claim 16 wherein said physiologically-acceptable water-soluble polymer comprises a polysaccharide. 18. The medical device of claim 17 wherein said polysaccharide comprises dextran. 19. The medical device of claim 16 wherein said conjugate is a coating. 20. The medical device of claim 16 wherein said conjugate is cast or molded into the medical device. 21. The medical device of claim 16 wherein said medical device is a replacement heart valve and wherein said fixed tissue is the fixed tissue of the replacement heart valve. 22. The medical device of claim 16 wherein said medical device is a replacement blood vessel and said fixed tissue is the fixed tissue of the replacement blood vessel. 23. The medical device of claim 16 wherein said fixed tissue has been fixed by treatment with glutaraldehyde. 24. The medical device of claim 16 wherein said fixed tissue has been treated with a reducing agent. 25. The medical device of claim 24 wherein the reducing agent is cyanoborohydride. 26. The medical device of claim 16 wherein said albumin-binding dye comprises an aromatic albumin-binding dye. 27. The medical device of claim 26 wherein said aromatic albumin-binding dye comprises a diazo dye, a sulfonic acid dye, or the physiologically acceptable salts thereof. 28. The medical device of claim 27 wherein said aromatic albumin-binding dye is selected from the group consisting of 1-Amino4((4-((4-chloro-6-((3(or 4)-sulfophenyl)amino)-1,3,5-triazin-2-yl)amino)-3-sulfophenyl)amino)-9,10- dihydro-9,10-dioxo-2-anthracenesulfonic acid, 6,6'-(3,3'-Diamethyl (1,1'-biphenyl)-4,4'diyl)bis(azo))bis(4-amino-5-hydroxy-1,3-naphthalene disulfonic acid) tetrasodium salt, 3,3'-(3,3'-Dimethyl(1,1'-biphenyl)-4,4'diyl)bis(azo))bis(5-amino-4 hydroxy-2,7-naphthalene disulfonic acid) tetrasodium salt, 4,4'-(3H-2,1-Benzoaxathiol-3-ylidene)bis(2,6-dibromo-3-methylphenol)S,S-di oxide, 4,4'-(3H-2,1-benzoaxathiol-3-ylidene)bis(2-bromo-6-methylphenol) S,S-dioxide, 4-(((4-dimethylamino) phenyl)azo)benzene-sulfonic acid sodium salt, 2-(4'-hydroxyazobenzene)benzoic acid, Procion red H-E 3B and mixtures thereof. 29. A method of increasing the albumin-binding ability of a implantable medical device comprising fixed tissue, said method comprising the step of: a. incorporating into said fixed tissue an amount of an albumin-binding dye; wherein the amount of the albumin-binding dye is effective to form a coating of endogenous albumin on a surface of said fixed tissue when the surface is in contact with a physiological fluid containing albumin. 30. The method of claim 29 wherein the albumin-binding dye comprises an aromatic albumin-binding dye. 31. The method of claim 30 wherein the aromatic albumin-binding dye comprises a diazo dye, a sulfonic acid dye, or the physiologically acceptable salts thereof. 32. The method of claim 31 wherein the aromatic albumin-binding dye is selected from the group consisting of 1-Amino-4((4-((4-chloro-6-((3(or 4)-sulfophenyl) amino)-1,3,5-triazin-2-yl)amino)-3-sulfophenyl)amino)-9,10-dihydro-9,10-di oxo-2-anthracenesulfonic acid, 6,6'-(3,3'-Diamethyl (1,1'-biphenyl)-4,4'diyl)bis(azo))bis(4-amino-5-hydroxy-1,3-naphthalene disulfonic acid) tetrasodium salt, 3,3'-(3,3'-Dimethyl(1,1'-biphenyl)-4,4'diyl)bis(azo))bis(5-amino-4 hydroxy-2,7-naphthalene disulfonic acid) tetrasodium salt, 4,4'-(3H-2,1-Benzoxathiol-3-ylidene)bis(2,6-dibromo-3-methylphenol)S,S-dio xide, 4,4'-(3H-2,1benzoxathiol-3-ylidene)bis(2-bromo-6-methylphenol) S,S-dioxide, 4-(((4-dimethylamino) phenyl)azo)benzene-sulfonic acid sodium salt, 2-(4'-hydroxyazobenzene) benzoic acid, Procion red H-E 3B, and mixtures thereof.

Details for Patent 5,509,932

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Grifols Therapeutics Llc	ALBUKED, PLASBUMIN-20, PLASBUMIN-25, PLASBUMIN-5	albumin (human)	For Injection	101138	10/21/1942		2040-01-28
Baxalta Us Inc.	BUMINATE, FLEXBUMIN	albumin (human)	Injection	101452	03/03/1954		2040-01-28
Csl Behring Ag	ALBURX	albumin (human)	Injection	102366	07/23/1976		2040-01-28