Claims for Patent: 7,129,210

Summary for Patent: 7,129,210

Title:	Tissue adhesive sealant
Abstract:	A tissue adhesive sealant includes a cross-linkable protein in a solution that when combined with a cross-linking agent solution including an aldehyde and amino acid containing species reactive with the aldehyde cross-links to form a seal. The sealant is well suited for bonding tissue alone or in combination with a patch. The ratio between the aldehyde and the amino acid containing species is between 20:1 and 1:1 on an aldehyde moiety:amino acid or peptide subunit molar basis. Particularly strong seals are formed when the protein and cross-linking agent are present in a molar ratio of between 15:1 and 1:1.
Inventor(s):	Lowinger; Johan (Dexter, MI), Lowinger; Bruno (Saline, MI), DeLustro; Frank (North Charleston, SC), Cox; David (Woodbury, MN), Browdie; David A. (Scranton, PA)
Assignee:	Covalent Medical, Inc. (Ann Arbor, MI)
Application Number:	10/894,609
Patent Claims:	1. A tissue adhesive kit consisting: a cross-linkable albumin protein consisting of albumin dissolved or suspended directly in aqueous solvent to form a protein solution; and a cross-linking agent solution comprising an aldehyde and an amino acid containing species reactive with said aldehyde, said aldehyde and said amino acid containing species being present in a ratio between 20:1 and 1:1 applied with said protein solution to form a tissue adhesive sealant. 2. The kit of claim 1 wherein said cross-linkable protein is a recombinant protein. 3. The kit of claim 1 wherein said protein is selected from the group consisting of: serum albumin and ovalbumin. 4. The kit of claim 3 wherein said serum albumin is human serum albumin. 5. The kit of claim 3 wherein said serum albumin is bovine serum albumin. 6. The kit of claim 1 wherein said protein is water soluble and present from 10 to 55 total weight percent of said solution. 7. The kit of claim 1 wherein said protein solution further comprises a suspension of collagen fibers present from 0.3 to 9 total percent of said protein solution. 8. The kit of claim 1 wherein said cross-linking agent solution has a pH of between 1.5 and 9. 9. The kit of claim 1 wherein said aldehyde has a plurality of aldehyde moieties therein. 10. The of claim 9 wherein said aldehyde has two aldehyde moieties. 11. The kit of claim 10 further comprising a lesser amount of a second aldehyde having at least three aldehyde moieties therein. 12. The kit of claim 1 wherein said aldehyde is selected from the group consisting of: (CH.sub.2).sub.n(CHO).sub.2 where n is an integer between 0 and 8, and C.sub.5 C.sub.8 cycloalkane dione. 13. The kit of claim 1 wherein said aldehyde is glutaraldehyde. 14. The kit of claim 1 wherein said amino acid containing species is selected from the group consisting of an amino acid, a dipeptide, a tripeptide, a polypeptide, a protein, and a glycoprotein. 15. The kit of claim 1 wherein said amino acid containing species is an amino acid having a residue selected from the group consisting of acidic, aliphatic, and amide. 16. The kit of claim 14 wherein said amino acid containing species has the formula: ##STR00002## where Q is CH.sub.2 or a nullity; R.sup.1 is independently in each occurrence H, Na, K, C.sub.2 C.sub.6 alkyl; R.sup.2 is independently H, C.sub.1 C.sub.20 alkyl group, a C.sub.0 C.sub.4 alkyl group having a substituent selected sulfonate, carboxylate, hydroxyl, quaternary amines, a radioisotopic ion, a magnetically detectable ion, an antibiotic moiety and an antibody; and n is an integer between 1 and 6 inclusive; hydrohalide salts thereof; and combinations thereof. 17. The kit of claim 12 wherein said amino acid is selected from the group consisting of: L-glutamic acid and L-aspartic acid. 18. The kit of claim 1 wherein said aldehyde:amino acid containing species molar ratio is between 10:1 and 4:1. 19. The kit of claim 1 wherein said aldehyde:amino acid containing species molar ratio is between 8:1 and 6:1. 20. The kit of claim 1 further comprising a pharmaceutical agent. 21. The kit of claim 1 further comprising a patch material suspension. 22. The kit of claim 21 wherein said suspension is collagen. 23. The of claim 21 wherein said suspension is admixed with said cross-linkable protein. 24. The kit of claim 21 further comprising a foaming agent. 25. The kit of claim 24 further comprising a propellant. 26. The kit of claim 1 further comprising a patch, the patch including a first and a second rupturable capsule, the first capsule containing the cross-linkable protein and the second capsule containing the cross-linking agent solution. 27. A tissue adhesive kit consisting: a cross-linkable protein selected from the group of casein, globulin, or gelatin consisting of said cross-linkable protein dissolved or suspended directly in aqueous solvent to form a protein solution or suspension; a cross-linking agent solution comprising an aldehyde and an amino acid containing species reactive with said aldehyde, said aldehyde and said amino acid containing species being present in a ratio between 20:1 and 1:1. 28. The kit of claim 27 wherein said cross-linkable protein is a recombinant protein. 29. The kit of claim 27 wherein said protein suspension further comprises collagen fibers present from 0.3 to 9 total percent of said suspension. 30. The kit of claim 27 wherein said solution containing said cross-linking agent solution has a pH of between 1.5 and 9. 31. The kit of claim 27 wherein said aldehyde has a plurality of aldehyde moieties therein. 32. The kit of claim 31 wherein said aldehyde has two aldehyde moieties. 33. The kit of claim 32 further comprising a lesser amount of a second aldehyde having at least three aldehyde moieties therein. 34. The kit of claim 27 wherein said aldehyde is selected from the group consisting of: (CH.sub.2).sub.n(CHO).sub.2 where n is an integer between 0 and 8, and C.sub.5 C.sub.8 cycloalkane dione. 35. The kit of claim 27 wherein said aldehyde is glutaraldehyde. 36. The kit of claim 27 wherein said amino acid containing species is selected from the group consisting of an amino acid, a dipeptide, a tripeptide, a polypeptide, a protein, and a glycoprotein. 37. The kit of claim 27 wherein said amino acid containing species is an amino acid having a residue selected from the group consisting of acidic, aliphatic, and amide. 38. The kit of claim 36 wherein said amino acid containing species has the formula: ##STR00003## where Q is CH.sub.2 or a nullity; R.sup.1 is independently in each occurrence H, Na, K, C.sub.2 C.sub.6 alkyl; R.sup.2 is independently H, C.sub.1 C.sub.20 alkyl group, a C.sub.0 C.sub.4 alkyl group having a substituent selected sulfonate, carboxylate, hydroxyl, quaternary amines, radioisotopic ion, a magnetically detectable ion, an antibiotic moiety and an antibody; and n is an integer between 1 and 3 inclusive; hydrohalide salts thereof; and combinations thereof. 39. The kit of claim 35 wherein said amino acid is selected from the group consisting of: L-glutamic acid and L-aspartic acid. 40. The kit of claim 27 wherein said aldehyde:amino acid containing species molar ratio is between 10:1 and 4:1. 41. The kit of claim 27 wherein said aldehyde:amino acid containing species molar ratio is between 8:1 and 6:1. 42. The kit of claim 27 further comprising a pharmaceutical agent. 43. The kit of claim 27 further comprising a patch material suspension. 44. The kit of claim 43 wherein said suspension is collagen. 45. The kit of claim 43 wherein said suspension is admixed with cross-linkable protein. 46. The kit of claim 43 further comprising a foaming agent. 47. The kit of claim 43 further comprising a propellant. 48. The kit of claim 27 further comprising a patch, the patch including a first and a second rupturable capsule, the first capsule containing said cross-linkable protein and the second capsule containing the cross-linking agent solution. 49. A tissue adhesive kit consisting: a cross-linkable suspension of collagen fiber protein consisting of collagen fiber protein suspended directly in aqueous solvent at 0.3 to 9 total weight percent to form a protein suspension; and a cross-linking agent solution comprising an aldehyde and an amino acid containing species reactive with said aldehyde, said aldehyde and said amino acid containing species being present in a ratio between 20:1 and 1:1. 50. The kit of claim 49 wherein said cross-linkable protein is a recombinant protein. 51. The kit of claim 49 wherein said solution containing said cross-linking agent solution has a pH of between 1.5 and 9. 52. The kit of claim 49 wherein said aldehyde has a plurality of aldehyde moieties therein. 53. The kit of claim 52 wherein said aldehyde has two aldehyde moieties. 54. The kit of claim 53 further comprising a lesser amount of a second aldehyde having at least three aldehyde moieties therein. 55. The kit of claim 49 wherein said aldehyde is selected from the group consisting of: (CH.sub.2).sub.n(CHO).sub.2 where n is an integer between 0 and 8, and C.sub.5 C.sub.8 cycloalkane dione. 56. The kit of claim 49 wherein said aldehyde is glutaraldehyde. 57. The kit of claim 49 wherein said amino acid containing species is selected from the group consisting of an amino acid, a dipeptide, a tripeptide, a polypeptide, a protein, and a glycoprotein. 58. The kit of claim 49 wherein said amino acid containing species is an amino acid having a residue selected from the group consisting of acidic, aliphatic, and amide. 59. The kit of claim 57 wherein said amino acid containing species has the formula: ##STR00004## where Q is CH.sub.2 or a nullity; R.sup.1 is independently in each occurrence H, Na, K, C.sub.2 C.sub.6 alkyl; R.sup.2 is independently H, C.sub.1 C.sub.20 alkyl group, a C.sub.0 C.sub.4 alkyl group having a substituent selected sulfonate, carboxylate, hydroxyl, quaternary amines, a radioisotopic ion, a magnetically detectable ion, an antibiotic moiety and an antibody; and n is an integer between 1 and 6 inclusive; hydrohalide salts thereof; and combinations thereof. 60. The kit of claim 56 wherein said amino acid is selected from the group consisting of: L-glutamic acid and L-aspartic acid. 61. The kit of claim 49 wherein said aldehyde:amino acid containing species molar ratio is between 10:1 and 4:1. 62. The kit of claim 49 further comprising a pharmaceutical agent. 63. The kit of claim 49 further comprising a patch material suspension. 64. The kit of claim 63 wherein said suspension is collagen. 65. The kit of claim 63 wherein said suspension is admixed with cross-linkable protein. 66. The kit of claim 63 further comprising a foaming agent. 67. The kit of claim 66 further comprising a propellant. 68. The kit of claim 49 further comprising a patch, the patch including a first and a second rupturable capsule, the first capsule containing the cross-linkable protein and the second capsule containing the cross-linking agent solution.

Details for Patent 7,129,210

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		2023-07-23
Baxalta Us Inc.	BUMINATE, FLEXBUMIN	albumin (human)	Injection	101452	03/03/1954		2023-07-23
Csl Behring Ag	ALBURX	albumin (human)	Injection	102366	07/23/1976		2023-07-23
Grifols Biologicals Llc	ALBUTEIN	albumin (human)	Injection	102478	08/15/1978		2023-07-23
Instituto Grifols, S.a.	HUMAN ALBUMIN GRIFOLS	albumin (human)	Injection	103352	02/17/1995		2023-07-23
Instituto Grifols, S.a.	HUMAN ALBUMIN GRIFOLS	albumin (human)	Injection	103352	06/11/2003		2023-07-23