Patent GB1277107A successfully refreshed from Google Patents.
Patent US20040063613A1 successfully refreshed from Google Patents.
US20040063613A1
Expired / Lapsed
US
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Methods and compositions for sealing tissue leaks
Assignee: Individual
•
Filing: 2003-09-30
•
Granted: —
•
Expires: 2023-09-30
Abstract
Abstract The invention provides methods and compositions that are useful for adhering biological and/or synthetic tissues, sealing fluid and/or gaseous leaks in biological and/or synthetic tissues, and preparing implants useful for delivery of a bioactive molecule such as a drug, for bulking applications, or for tissue prostheses. The present invention also relates to bio-erodable adhesive or occluding compositions and methods of using the same.
Inventors
- 👤 James Rolke
- 👤 Luis Burzio
- 👤 Eugene Pashkovski
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 04:09
CPC Classifications
A; A61; A61L; A61L24/00; A61L24/04; A61L24/10; A61L24/108; A61L24/001; A61L24/043
Claims Analysis
Total Claims: 182
Claim 1
Independent Claim
86 words
1 . A method for bonding tissue or sealing a fluid or gas leak in tissue comprising the steps of: (a) providing a protein, a surfactant, and a lipid in a liquid carrier; (b) providing a crosslinker capable of crosslinking the protein; (c) preparing a sealant by mixing the protein with the crosslinker under conditions which permit crosslinking of the protein; and (d) applying the sealant of (c) to a tissue, thereby to bond the tissue or seal a fluid or gas leak in the tissue.
Claim 2
Dependent Claim
86 words
1 . A method for bonding tissue or sealing a fluid or gas leak in tissue comprising the steps of: (a) providing a protein, a surfactant, and a lipid in a liquid carrier; (b) providing a crosslinker capable of crosslinking the protein; (c) preparing a sealant by mixing the protein with the crosslinker under conditions which permit crosslinking of the protein; and (d) applying the sealant of (c) to a tissue, thereby to bond the tissue or seal a fluid or gas leak in the tissue.
Claim 3
Dependent Claim
77 words
2 . A method for bonding tissue or sealing a fluid or gas leak in tissue comprising the steps of: (a) applying to a tissue locus: i. a protein preparation; ii. at least one preparation selected from the group consisting of a surfactant preparation and a lipid preparation; and iii. a crosslinker preparation; and (b) permitting the preparations to form crosslinks, thereby to bond said tissue or to seal a fluid or gas leak in said tissue.
Claim 4
Dependent Claim
77 words
2 . A method for bonding tissue or sealing a fluid or gas leak in tissue comprising the steps of: (a) applying to a tissue locus: i. a protein preparation; ii. at least one preparation selected from the group consisting of a surfactant preparation and a lipid preparation; and iii. a crosslinker preparation; and (b) permitting the preparations to form crosslinks, thereby to bond said tissue or to seal a fluid or gas leak in said tissue.
Claim 5
Dependent Claim
28 words
3 . The method of claim 1 or 2 , wherein the protein is selected from the group consisting of albumin, collagen, gelatin, globulin, elastin, protamine, and histone.
Claim 6
Dependent Claim
23 words
4 . The method of claim 3 , wherein the concentration of the protein is between about 3% (w/w) and about 50% (w/w).
Claim 7
Dependent Claim
28 words
5 . The method of claim 4 , wherein the protein is albumin and wherein the concentration of albumin is between about 20% (w/w) and about 50% (w/w).
Claim 8
Dependent Claim
28 words
6 . The method of claim 4 , wherein the protein is collagen and wherein the concentration of collagen is between about 3% (w/w) and about 12% (w/w).
Claim 9
Dependent Claim
30 words
7 . The method of claim 4 , wherein the protein is a globulin and wherein the concentration of the globulin is between about 15% (w/w) and about 30% (w/w).
Claim 10
Dependent Claim
24 words
8 . The method of claim 1 or 2 , wherein the concentration of surfactant is between about 0.05% (w/w) and about 10% (w/w).
Claim 11
Dependent Claim
15 words
9 . The method of claim 8 , wherein the surfactant is an ionic surfactant.
Claim 12
Dependent Claim
30 words
10 . The method of claim 9 , wherein the ionic surfactant is selected from the group consisting of alkanoic acids, alkylsulfonic acids, alkyl amines, perfluoroalkanoic acids, and perfluoroalkylsulfonic acids.
Claim 13
Dependent Claim
38 words
11 . The method of claim 10 , wherein the ionic surfactant comprises an alkyl group with a chemical formula CH 3 (CH 2 ) n , wherein n is an integer from about 6 to about 18.
Claim 14
Dependent Claim
26 words
12 . The method of claim 10 , wherein the alkanoic acid is selected from the group consisting of octanoic acid, dodecanoic acid and palmitic acid.
Claim 15
Dependent Claim
16 words
13 . The method of claim 10 , wherein the alkylsulfonic acid is sodium lauryl sulfate.
Claim 16
Dependent Claim
44 words
14 . The method of claim 10 , wherein the perfluoroalkanoic acid has a structure selected from the group consisting of CF 3 (CF 2 ) n —COO—, and —OOC(CF 2 ) n —COO—, wherein n is an integer from one to about sixteen.
Claim 17
Dependent Claim
15 words
15 . The method of claim 10 , wherein the perfluoroalkanoic acid is perfluorooctanoic acid.
Claim 18
Dependent Claim
17 words
16 . The method of claim 1 or 2 , wherein the surfactant is a nonionic surfactant.
Claim 19
Dependent Claim
36 words
17 . The method of claim 16 , wherein the nonionic surfactant is selected from the group consisting of an alkyl or perfluoroalkyl-polyoxyethylene ether, a polyoxyethylene ester, a polyoxyethylene sorbitan, and an alkyl aryl polyether alcohol.
Claim 20
Dependent Claim
16 words
18 . The method of claim 17 , wherein the alkyl aryl polyether alcohol is tyloxapol.
Claim 21
Dependent Claim
25 words
19 . The method of claim 1 or 2 , wherein the concentration of the lipid is from about 0.1% (w/v) to about 10% (w/v).
Claim 22
Dependent Claim
17 words
20 . The method of claim 1 or 2 , wherein the lipid is a naturally-occurring lipid.
Claim 23
Dependent Claim
17 words
21 . The method of claim 1 or 2 , wherein the lipid is a synthetic lipid.
Claim 24
Dependent Claim
40 words
22 . The method of claim 1 or 2 , wherein the lipid is a hydrophobically-modified glycerol derivative of a molecule selected from the group consisting of phosphocholines, phosphatidic acid, phosphatidylethanolamine, phosphatidyl inositol, glycerol, bile acids, and long chain alcohols.
Claim 25
Dependent Claim
56 words
23 . The method of claim 22 , wherein the hydrophobically-modified glycerol derivative of a phosphocholine has the structure R 1 —C(O)—O—CH 2 —(R 2 —C(O)—O)CH 2 —CH 2 —OPO 2 O(CH 2 ) 2 —N(CH 3 ) 3 , wherein R 1 and R 2 are chemical groups that do not react with a carbodiimide.
Claim 26
Dependent Claim
49 words
24 . The method of claim 22 , wherein the hydrophobically-modified glycerol derivative of a phosphatidic acid has the structure R 1 —C(O)—O—CH 2 —(R 2 —C(O)—O)CH 2 —CH 2 —OPO 2 H, wherein R 1 and R 2 are chemical groups that do not react with a carbodiimide.
Claim 27
Dependent Claim
54 words
25 . The method of claim 22 , wherein the hydrophobically-modified glycerol derivative of a phosphatidylethanolamine has the structure R 1 —C(O)—O—CH 2 —(R 2 —C(O)—O)CH 2 —CH 2 —OPO 2 O(CH 2 ) 2 —NH 2 , wherein R 1 and R 2 are chemical groups that do not react with a carbodiimide.
Claim 28
Dependent Claim
59 words
26 . The method of claim 22 , wherein the hydrophobically modified glycerol derivative of a phosphatidyl inositol has the structure of R 1 —C(O)—O—CH 2 —(R 2 —C(O)—O)CH 2 —CH 2 —OPO 2 O(C 6 ) 2 H 11 O 5 , wherein R 1 and R 2 are chemical groups that do not react with a carbodiimide.
Claim 29
Dependent Claim
61 words
27 . The method of claim 23 - 26 , wherein the structure of R 1 is CH 3 (CH 2 ) n —, wherein the structure of R 2 is CH 3 (CH 2 ) m —, wherein n is an integer from about 4 to about 22, and wherein m is an integer from about 4 to about 22.
Claim 30
Dependent Claim
19 words
28 . The method of claim 23 , wherein the hydrophobically-modified glycerol derivative of a phosphocholine is dipalmitoylphosphatidyl choline.
Claim 31
Dependent Claim
34 words
29 . The method of claim 22 , wherein the bile acid is selected from the group consisting of cholic acid, chenodeoxycholic acid, cholic acid methyl ester, dehydrocholic acid, deoxycholic acid, and lithocholic acid.
Claim 32
Dependent Claim
34 words
30 . The method of claim 22 , wherein the long chain alcohol has the structure CH 3 (CH 2 ) n —OH, wherein n is an integer from about six to about twenty-two.
Claim 33
Dependent Claim
21 words
31 . The method of claim 1 or 2 , wherein the crosslinker is a zero-length, homobifunctional, heterobifunctional, or multifunctional crosslinker.
Claim 34
Dependent Claim
24 words
32 . The method of claim 31 , wherein the zero-length crosslinker is selected from the group consisting of carbodiimides, isoxazolium salts, and carbonyldiimidazole
Claim 35
Dependent Claim
16 words
33 . The method of claim 31 , wherein the carbodiimide is 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)
Claim 36
Dependent Claim
21 words
34 . The method of claim 32 , wherein the concentration of EDC is from about 5 to about 500 mg/mL.
Claim 37
Dependent Claim
27 words
35 . The method of claim 31 , wherein the zerolength crosslinker is selected from the group consisting of a carbodiimide mediated reactive ester and a carbamate.
Claim 38
Dependent Claim
18 words
36 . The method of claim 35 , wherein the reactive ester is formed from N-hydroxysuccinimide or N-hydroxysulfosuccinimide.
Claim 39
Dependent Claim
19 words
37 . The method of claim 1 or 2 , wherein the surfactant is covalently attached to the protein.
Claim 40
Dependent Claim
20 words
38 . The method of claim 1 or 2 , wherein the surfactant is not covalently attached to the protein.
Claim 41
Dependent Claim
19 words
39 . The method of claim 1 or 2 , wherein the lipid is covalently attached to the protein.
Claim 42
Dependent Claim
20 words
40 . The method of claim 1 or 2 , wherein the lipid is not covalently attached to the protein.
Claim 43
Dependent Claim
26 words
41 . A kit for producing a protein-based tissue adhesive or sealant comprising: (a) a protein preparation; (b) a protein-degrading preparation; and (c) a crosslinker preparation.
Claim 44
Dependent Claim
26 words
41 . A kit for producing a protein-based tissue adhesive or sealant comprising: (a) a protein preparation; (b) a protein-degrading preparation; and (c) a crosslinker preparation.
Claim 45
Dependent Claim
40 words
42 . A kit for producing a protein-based tissue adhesive or sealant comprising: (a) a protein preparation; (b) a crosslinker preparation; and (c) at least one preparation selected from the group consisting of a surfactant preparation and a lipid preparation.
Claim 46
Dependent Claim
40 words
42 . A kit for producing a protein-based tissue adhesive or sealant comprising: (a) a protein preparation; (b) a crosslinker preparation; and (c) at least one preparation selected from the group consisting of a surfactant preparation and a lipid preparation.
Claim 47
Dependent Claim
27 words
43 . The kit of claim 42 further comprising at least one preparation selected from the group consisting of a tissue primer preparation and a protein-degrading preparation.
Claim 48
Dependent Claim
28 words
44 . The kit of claim 41 or 42 , wherein the protein is selected from the group consisting of albumin, collagen, gelatin, globulin, elastin, protamine, and histone.
Claim 49
Dependent Claim
23 words
45 . The kit of claim 44 , wherein the concentration of the protein is between about 3% (w/w) and about 50% (w/w).
Claim 50
Dependent Claim
28 words
46 . The kit of claim 45 , wherein the protein is albumin and wherein the concentration of albumin is between about 25% (w/w) and about 50% (w/w)
Claim 51
Dependent Claim
28 words
47 . The kit of claim 45 , wherein the protein is collagen and wherein the concentration of collagen is between about 3% (w/w) and about 12% (w/w).
Claim 52
Dependent Claim
30 words
48 . The kit of claim 45 , wherein the protein is a globulin and wherein the concentration of the globulin is between about 15% (w/w) and about 30% (w/w).
Claim 53
Dependent Claim
22 words
49 . The kit of claim 42 , wherein the concentration of surfactant is between about 0.05% (w/w) and about 10% (w/w).
Claim 54
Dependent Claim
15 words
50 . The kit of claim 42 , wherein the surfactant is an ionic surfactant.
Claim 55
Dependent Claim
30 words
51 . The kit of claim 50 , wherein the ionic surfactant is selected from the group consisting of alkanoic acids, alkylsulfonic acids, alkyl amines, perfluoroalkanoic acids, and perfluoroalkylsulfonic acids.
Claim 56
Dependent Claim
38 words
52 . The kit of claim 50 , wherein the ionic surfactant comprises an alkyl group with a chemical formula CH 3 (CH 2 ) n , wherein n is an integer from about 6 to about 18.
Claim 57
Dependent Claim
26 words
53 . The kit of claim 51 , wherein the alkanoic acid is selected from the group consisting of octanoic acid, dodecanoic acid and palmitic acid.
Claim 58
Dependent Claim
16 words
54 . The kit of claim 51 , wherein the alkylsulfonic acid is sodium lauryl sulfate.
Claim 59
Dependent Claim
43 words
55 . The kit of claim 51 , wherein the perfluoroalkanoic acid has a structure-selected from the group consisting of CF 3 (CF 2 ) n —COO—, and —OOC(CF 2 ) n —COO—, wherein n is an integer from one to about sixteen.
Claim 60
Dependent Claim
15 words
56 . The kit of claim 51 , wherein the perfluoroalkanoic acid is perfluorooctanoic acid.
Claim 61
Dependent Claim
15 words
57 . The kit of claim 42 , wherein the surfactant is a nonionic surfactant.
Claim 62
Dependent Claim
36 words
58 . The kit of claim 57 , wherein the nonionic surfactant is selected from the group consisting of an alkyl or perfluoroalkyl-polyoxyethylene ether, a polyoxyethylene ester, a polyoxyethylene sorbitan, and an alkyl aryl polyether alcohol.
Claim 63
Dependent Claim
16 words
59 . The kit of claim 57 , wherein the alkyl aryl polyether alcohol is tyloxapol.
Claim 64
Dependent Claim
23 words
60 . The kit of claim 42 , wherein the concentration of the lipid is from about 0.1% (w/v) to about 10% (w/v).
Claim 65
Dependent Claim
15 words
61 . The kit of claim 42 , wherein the lipid is a naturally-occurring lipid.
Claim 66
Dependent Claim
15 words
62 . The kit of claim 42 , wherein the lipid is a synthetic lipid.
Claim 67
Dependent Claim
38 words
63 . The kit of claim 42 , wherein the lipid is a hydrophobically-modified glycerol derivative of a molecule selected from the group consisting of phosphocholines, phosphatidic acid, phosphatidylethanolamine, phosphatidyl inositol, glycerol, bile acids, and long chain alcohols.
Claim 68
Dependent Claim
56 words
64 . The kit of claim 63 , wherein the hydrophobically-modified glycerol derivative of a phosphocholine has the structure R 1 —C(O)—O—CH 2 —(R 2 C(O)—O)CH 2 —CH 2 —OPO 2 O(CH 2 ) 2 —N(CH 3 ) 3 , wherein R 1 and R 2 are chemical groups that do not react with a carbodiimide.
Claim 69
Dependent Claim
49 words
65 . The kit of claim 63 , wherein the hydrophobically-modified glycerol derivative of a phosphatidic acid has the structure R 1 —C(O)—O—CH 2 —(R 2 —C(O)—O)CH 2 —CH 2 —OPO 2 H, wherein R 1 and R 2 are chemical groups that do not react with a carbodiimide.
Claim 70
Dependent Claim
54 words
66 . The kit of claim 63 , wherein the hydrophobically-modified glycerol derivative of a phosphatidylethanolamine has the structure R 1 —C(O)—O—CH 2 (R 2 C(O)—O)CH 2 —CH 2 —OPO 2 O(CH 2 ) 2 —NH 2 , wherein R 1 and R 2 are chemical groups that do not react with a carbodiimide.
Claim 71
Dependent Claim
59 words
67 . The kit of claim 63 , wherein the hydrophobically modified glycerol derivative of a phosphatidyl inositol has the structure of R 1 —C(O)—O—CH 2 —(R 2 —C(O)—O)CH 2 —CH 2 —OPO 2 O(C 6 ) 2 H 11 O 5 , wherein R 1 and R 2 are chemical groups that do not react with a carbodiimide.
Claim 72
Dependent Claim
61 words
68 . The kit of claim 64 - 67 , wherein the structure of R 1 is CH 3 (CH 2 ) n —, wherein the structure of R 2 is CH 3 (CH 2 ) m —, wherein n is an integer from about 4 to about 22, and wherein m is an integer from about 4 to about 22.
Claim 73
Dependent Claim
19 words
69 . The kit of claim 64 , wherein the hydrophobically-modified glycerol derivative of a phosphocholine is dipalmitoylphosphatidyl choline.
Claim 74
Dependent Claim
34 words
70 . The kit of claim 63 , wherein the bile acid is selected from the group consisting of cholic acid, chenodeoxycholic acid, cholic acid methyl ester, dehydrocholic acid, deoxycholic acid, and lithocholic acid.
Claim 75
Dependent Claim
34 words
71 . The kit of claim 63 , wherein the long chain alcohol has the structure CH 3 (CH 2 ) n —OH, wherein n is an integer from about six to about twenty-two.
Claim 76
Dependent Claim
21 words
72 . The kit of claim 41 or 42 , wherein the crosslinker is a zero-length, homobifunctional, heterobifunctional, or multifunctional crosslinker.
Claim 77
Dependent Claim
24 words
73 . The kit of claim 72 , wherein the zero-length crosslinker is selected from the group consisting of carbodiimides, isoxazolium salts, and carbonyldiimidazole.
Claim 78
Dependent Claim
16 words
74 . The kit of claim 73 , wherein the carbodiimide is 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC).
Claim 79
Dependent Claim
21 words
75 . The kit of claim 74 , wherein the concentration of EDC is from about 5 to about 500 mg/mL.
Claim 80
Dependent Claim
27 words
76 . The kit of claim 72 , wherein the zero-length crosslinker is selected from the group consisting of a carbodiimide mediated reactive ester and a carbamate.
Claim 81
Dependent Claim
18 words
77 . The kit of claim 76 , wherein the reactive ester is formed from N-hydroxysuccinimide or N-hydroxysulfosuccinimide.
Claim 82
Dependent Claim
17 words
78 . The kit of claim 42 , wherein the surfactant is covalently attached to the protein.
Claim 83
Dependent Claim
18 words
79 . The kit of claim 42 , wherein the surfactant is not covalently attached to the protein.
Claim 84
Dependent Claim
17 words
80 . The kit of claim 42 , wherein the lipid is covalently attached to the protein.
Claim 85
Dependent Claim
18 words
81 . The kit of claim 42 , wherein the lipid is not covalently attached to the protein.
Claim 86
Dependent Claim
35 words
82 . A platelet-free composition for use as a tissue sealant or adhesive comprising a protein solution and at least one preparation selected from the group consisting of a surfactant preparation and a lipid preparation.
Claim 87
Dependent Claim
35 words
82 . A platelet-free composition for use as a tissue sealant or adhesive comprising a protein solution and at least one preparation selected from the group consisting of a surfactant preparation and a lipid preparation.
Claim 88
Dependent Claim
18 words
83 . The composition of claim 82 comprising a protein solution, a surfactant preparation and a lipid preparation.
Claim 89
Dependent Claim
26 words
84 . The composition of claim 82 , wherein the protein is selected from the group consisting of albumin, collagen, gelatin, globulin, elastin, protamine, and histone.
Claim 90
Dependent Claim
22 words
85 . The composition of claim 84 , wherein the concentration of the protein is between about 3% (w/w) and 50% (w/w).
Claim 91
Dependent Claim
28 words
86 . The composition of claim 85 , wherein the protein is albumin and wherein the concentration of albumin is between about 25% (w/w) and about 50% (w/w)
Claim 92
Dependent Claim
28 words
87 . The composition of claim 85 , wherein the protein is collagen and wherein the concentration of collagen is between about 3% (w/w) and about 12% (w/w).
Claim 93
Dependent Claim
30 words
88 . The composition of claim 85 , wherein the protein is a globulin and wherein the concentration of the globulin is between about 15% (w/w) and about 30% (w/w).
Claim 94
Dependent Claim
22 words
89 . The composition of claim 82 , wherein the concentration of surfactant is between about 0.05% (w/w) and about 10% (w/w).
Claim 95
Dependent Claim
15 words
90 . The composition of claim 82 , wherein the surfactant is an ionic surfactant.
Claim 96
Dependent Claim
30 words
91 . The composition of claim 90 , wherein the ionic surfactant is selected from the group consisting of alkanoic acids, alkylsulfonic acids, alkyl amines, perfluoroalkanoic acids, and perfluoroalkylsulfonic acids.
Claim 97
Dependent Claim
37 words
92 . The composition of claim 91 , wherein the ionic surfactant comprises an alkyl group with a chemical formula CH 3 (CH 2 ) n, wherein n is an integer from about 6 to about 18.
Claim 98
Dependent Claim
26 words
93 . The composition of claim 91 , wherein the alkanoic acid is selected from the group consisting of octanoic acid, dodecanoic acid and palmitic acid.
Claim 99
Dependent Claim
16 words
94 . The composition of claim 91 , wherein the alkylsulfonic acid is sodium lauryl sulfate.
Claim 100
Dependent Claim
44 words
95 . The composition of claim 91 , wherein the perfluoroalkanoic acid has a structure selected from the group consisting of CF 3 (CF 2 ) n —COO—, and —OOC(CF 2 ) n —COO—, wherein n is an integer from one to about sixteen.
Claim 101
Dependent Claim
15 words
96 . The composition of claim 91 , wherein the perfluoroalkanoic acid is perfluorooctanoic acid.
Claim 102
Dependent Claim
15 words
97 . The composition of claim 82 , wherein the surfactant is a nonionic surfactant.
Claim 103
Dependent Claim
36 words
98 . The composition of claim 97 , wherein the nonionic surfactant is selected from the group consisting of an alkyl or perfluoroalkyl-polyoxyethylene ether, a polyoxyethylene ester, a polyoxyethylene sorbitan, and an alkyl aryl polyether alcohol.
Claim 104
Dependent Claim
16 words
99 . The composition of claim 98 , wherein the alkyl aryl polyether alcohol is tyloxapol.
Claim 105
Dependent Claim
23 words
100 . The composition of claim 82 , wherein the concentration of the lipid is from about 0.1% (w/v) to about 10% (w/v).
Claim 106
Dependent Claim
15 words
101 . The composition of claim 82 , wherein the lipid is a naturally-occurring lipid.
Claim 107
Dependent Claim
15 words
102 . The composition of claim 82 , wherein the lipid is a synthetic lipid.
Claim 108
Dependent Claim
38 words
103 . The composition of claim 82 , wherein the lipid is a hydrophobically-modified glycerol derivative of a molecule selected from the group consisting of phosphocholines, phosphatidic acid, phosphatidylethanolamine, phosphatidyl inositol, glycerol, bile acids, and long chain alcohols.
Claim 109
Dependent Claim
56 words
104 . The composition of claim 103 , wherein the hydrophobically-modified glycerol derivative of a phosphocholine has the structure R 1 —C(O)—O—CH 2 —(R 2 —C(O)—O)CH 2 —CH 2 —OPO 2 O(CH 2 ) 2 —N(CH 3 ) 3 , wherein R 1 and R 2 are chemical groups that do not react with a carbodiimide.
Claim 110
Dependent Claim
49 words
105 . The composition of claim 103 , wherein the hydrophobically-modified glycerol derivativ of a phosphatidic acid has the structur R 1 —C(O)—O—CH 2 —(R 2 —C(O)—O)CH 2 —CH 2 —OPO 2 H, wherein R 1 and R 2 are chemical groups that do not react with a carbodiimide.
Claim 111
Dependent Claim
54 words
106 . The composition of claim 103 , wherein the hydrophobically-modified glycerol derivative of a phosphatidylethanolamine has the structure R 1 —C(O)—O—CH 2 —(R 2 —C(O)—O)CH 2 —CH 2 —OPO 2 O(CH 2 ) 2 —NH 2 , wherein R 1 and R 2 are chemical groups that do not react with a carbodiimide.
Claim 112
Dependent Claim
59 words
107 . The composition of claim 103 , wherein the hydrophobically modified glycerol derivative of a phosphatidyl inositol has the structure of R 1 —C(O)—O—CH 2 —(R 2 —C(O)—O)CH 2 —CH 2 —OPO 2 O(C 6 ) 2 H 11 O 5 , wherein R 1 and R 2 are chemical groups that do not react with a carbodiimide.
Claim 113
Dependent Claim
61 words
108 . The composition of claim 104 - 107 , wherein the structure of R 1 is CH 3 (CH 2 ) n —, wherein the structure of R 2 is CH 3 (CH 2 ) m —, wherein n is an integer from about 4 to about 22, and wherein m is an integer from about 4 to about 22.
Claim 114
Dependent Claim
19 words
109 . The composition of claim 104 , wherein the hydrophobically-modified glycerol derivative of a phosphocholine is dipalmitoylphosphatidyl choline.
Claim 115
Dependent Claim
34 words
110 . The composition of claim 103 , wherein the bile acid is selected from the group consisting of cholic acid, chenodeoxycholic acid, cholic acid methyl ester, dehydrocholic acid, deoxycholic acid, and lithocholic acid.
Claim 116
Dependent Claim
34 words
111 . The composition of claim 103 , wherein the long chain alcohol has the structure CH 3 (CH 2 ) n —OH, wherein n is an integer from about six to about twenty-two.
Claim 117
Dependent Claim
17 words
112 . The composition of claim 82 , wherein the surfactant is covalently attached to the protein.
Claim 118
Dependent Claim
18 words
113 . The composition of claim 82 , wherein the surfactant is not covalently attached to the protein.
Claim 119
Dependent Claim
17 words
114 . The composition of claim 82 , wherein the lipid is covalently attached to the protein.
Claim 120
Dependent Claim
18 words
115 . The composition of claim 82 , wherein the lipid is not covalently attached to the protein.
Claim 121
Dependent Claim
37 words
116 . A method for preparing a tissue to react with a protein-based tissue sealant or adhesive comprising the step of: applying a primer solution at a pH of about 3.0 to 9.0 to a tissue locus.
Claim 122
Dependent Claim
37 words
116 . A method for preparing a tissue to react with a protein-based tissue sealant or adhesive comprising the step of: applying a primer solution at a pH of about 3.0 to 9.0 to a tissue locus.
Claim 123
Dependent Claim
15 words
117 . The method of claim 116 , wherein the primer solution comprises a buffer.
Claim 124
Dependent Claim
14 words
118 . The method of claim 117 , wherein the buffer is morpholinoethanesulfonic acid.
Claim 125
Dependent Claim
14 words
119 . The method of claim 118 , wherein the pH is about 5.
Claim 126
Dependent Claim
17 words
120 . The method of claim 118 , wherein the concentration of the buffer is about 0.5M.
Claim 127
Dependent Claim
33 words
121 . A method for preparing a tissue to react with a protein-based tissue sealant or adhesive comprising the step of: applying a primer solution containing a protein crosslinker to a tissue locus.
Claim 128
Dependent Claim
33 words
121 . A method for preparing a tissue to react with a protein-based tissue sealant or adhesive comprising the step of: applying a primer solution containing a protein crosslinker to a tissue locus.
Claim 129
Dependent Claim
13 words
122 . The method of claim 121 , wherein the crosslinker is carbodiimide.
Claim 130
Dependent Claim
13 words
123 . The method of claim 122 , wherein the carbodiimide is EDC-HCl.
Claim 131
Dependent Claim
18 words
124 . The method of claim 121 , wherein the primer is a solution of carbodiimide and hydroxysuccinimide.
Claim 132
Dependent Claim
18 words
125 . The method of claim 124 , wherein the carbodiimide is EDC-HCl and the hydroxysuccinimide is N-hydroxysulfosuccinimide.
Claim 133
Dependent Claim
20 words
126 . The method of claim 121 , wherein the primer is a solution of a dialdehyde or a polyaldehyde.
Claim 134
Dependent Claim
17 words
127 . The method of claim 126 , wherein the primer comprises glutaraldehyde or a derivative thereof.
Claim 135
Dependent Claim
51 words
128 . A method for preparing a tissue to react with a protein-based tissue sealant or adhesive comprising the step of: applying a primer solution comprising a molecule that promotes contact between the sealant and a tissue, thereby promoting an increase in reactive surface area between the sealant and the tissue.
Claim 136
Dependent Claim
51 words
128 . A method for preparing a tissue to react with a protein-based tissue sealant or adhesive comprising the step of: applying a primer solution comprising a molecule that promotes contact between the sealant and a tissue, thereby promoting an increase in reactive surface area between the sealant and the tissue.
Claim 137
Dependent Claim
16 words
129 . The method of claim 128 , wherein the molecule interacts preferentially with fluorophilic surfaces.
Claim 138
Dependent Claim
15 words
130 . The method of claim 128 , wherein the molecule comprises a fluorophilic moiety.
Claim 139
Dependent Claim
16 words
131 . The method of claim 130 , wherein the fluorophilic moiety is a perfluoroalkanoic acid.
Claim 140
Dependent Claim
15 words
132 . The method of claim 131 , wherein the perfluoroalkanoic acid is perfluorooctanoic acid.
Claim 141
Dependent Claim
43 words
133 . A method for increasing the degradation rate, or reducing the persistence of a polymer-based tissue sealant or adhesive, comprising the step of: mixing a polymer degrading agent with a sealant or adhesive before applying the sealant or adhesive to a tissue.
Claim 142
Dependent Claim
43 words
133 . A method for increasing the degradation rate, or reducing the persistence of a polymer-based tissue sealant or adhesive, comprising the step of: mixing a polymer degrading agent with a sealant or adhesive before applying the sealant or adhesive to a tissue.
Claim 143
Dependent Claim
51 words
134 . A method for increasing the degradation rate, or reducing the persistence of a polymer-based tissue sealant or adhesive, comprising the step of: applying a polymer degrading agent to a sealant or adhesive at a tissue locus, thereby increasing the degradation rate of the sealant or adhesive at the tissue.
Claim 144
Dependent Claim
51 words
134 . A method for increasing the degradation rate, or reducing the persistence of a polymer-based tissue sealant or adhesive, comprising the step of: applying a polymer degrading agent to a sealant or adhesive at a tissue locus, thereby increasing the degradation rate of the sealant or adhesive at the tissue.
Claim 145
Dependent Claim
36 words
135 . The method of claim 133 or 134 , wherein the sealant or adhesive is selected from the group consisting of protein-based, carbohydrate-based, nucleotide-based, and synthetic polymer-based tissue sealants or adhesives or any combination thereof.
Claim 146
Dependent Claim
16 words
136 . The method of claim 133 , wherein said tissue sealant or adhesive is protein-based.
Claim 147
Dependent Claim
22 words
137 . The method of claim 136 , wherein the protein is selected from the group consisting of albumin, collagen, and globulin.
Claim 148
Dependent Claim
17 words
138 . The method of claim 133 or 134 , wherein the sealant or adhesive is carbohydrate-based.
Claim 149
Dependent Claim
24 words
139 . The method of claim 138 , wherein the carbohydrate is selected from the group consisting of natural and synthetic poly- and oligo-saccharides.
Claim 150
Dependent Claim
30 words
140 . The method of claim 139 , wherein the carbohydrate is selected from the group consisting of amylose, amylopectin, alginate, agarose, cellulose, carboxymethylcellulose, carboxymethylamylose, chitin, chitosan, pectin, and dextran.
Claim 151
Dependent Claim
17 words
141 . The method of claim 133 or 134 , wherein the degradation agent is an enzyme.
Claim 152
Dependent Claim
21 words
142 . The method of claim 141 , wherein the enzyme is selected from the group consisting of proteases and glucanases.
Claim 153
Dependent Claim
30 words
143 . The method of claim 142 , wherein the protease is selected from the group consisting of bromelain, trypsin, chymotrypsin, clostripain, collagenase, elastase, papain, proteinase K, pepsin, and subtilisin.
Claim 154
Dependent Claim
13 words
144 . The method of claim 143 , wherein the protease is trypsin.
Claim 155
Dependent Claim
27 words
145 . The method of claim 142 , wherein the glucanase is selected from the group consisting of agarases, amylases, cellulases, chitinases, dextranases, hyaluranidases, lysozymes, and pectinases.
Claim 156
Dependent Claim
13 words
146 . The method of claim 145 , wherein the glucanase is cellulase.
Claim 157
Dependent Claim
32 words
147 . The method of claim 133 or 134 , wherein the degradation agent is provided in an amount sufficient to promote degradation of the tissue sealant or adhesive within forty days.
Claim 158
Dependent Claim
35 words
148 . The method of claim 133 or 134 , wherein the degradation agent is provided in an inactive form, and wherein the degradation agent is activated after its application to the sealant or adhesive.
Claim 159
Dependent Claim
42 words
149 . The method of claim 133 or 134 , wherein the tissue is selected from the group consisting of connective tissue, vascular tissue, pulmonary tissue, neural tissue, lymphatic tissue, dural tissue, spleen tissue, hepatic tissue, renal tissue, gastrointestinal tissue, and skin.
Claim 160
Dependent Claim
92 words
150 . A method for bonding tissue or sealing a fluid or gas leak in tissue comprising the steps of: (a) providing a solution comprising about 35% BSA, 5% DPPC, and 5% Tyloxapol; (b) providing a solution of about 200 mg/ml EDC; (c) preparing a sealant by mixing the solution of step (a) with the solution of step (b) in a ratio of about 10/1 (v/v); and (d) applying the sealant of step (c) to a tissue, thereby to bond the tissue or seal a fluid or gas leak in the tissue.
Claim 161
Dependent Claim
92 words
150 . A method for bonding tissue or sealing a fluid or gas leak in tissue comprising the steps of: (a) providing a solution comprising about 35% BSA, 5% DPPC, and 5% Tyloxapol; (b) providing a solution of about 200 mg/ml EDC; (c) preparing a sealant by mixing the solution of step (a) with the solution of step (b) in a ratio of about 10/1 (v/v); and (d) applying the sealant of step (c) to a tissue, thereby to bond the tissue or seal a fluid or gas leak in the tissue.
Claim 162
Dependent Claim
50 words
151 . A kit for producing a protein-based tissue adhesive or sealant comprising: (a) a solution comprising about 35% BSA; (b) a crosslinker preparation comprising about 20% EDC; and (c) at least one preparation selected from the group consisting of about 5% DPPC, about 5% Tyloxapol, and a combination thereof.
Claim 163
Dependent Claim
50 words
151 . A kit for producing a protein-based tissue adhesive or sealant comprising: (a) a solution comprising about 35% BSA; (b) a crosslinker preparation comprising about 20% EDC; and (c) at least one preparation selected from the group consisting of about 5% DPPC, about 5% Tyloxapol, and a combination thereof.
Claim 164
Dependent Claim
30 words
152 . A two-component kit for producing a protein-based tissue adhesive or sealant comprising: (a) a first protein preparation; and, (b) a second protein preparation mixed with a cross-linker preparation.
Claim 165
Dependent Claim
30 words
152 . A two-component kit for producing a protein-based tissue adhesive or sealant comprising: (a) a first protein preparation; and, (b) a second protein preparation mixed with a cross-linker preparation.
Claim 166
Dependent Claim
28 words
153 . The kit of claim 152 , wherein said first protein preparation is at an acid pH and said second protein preparation is at a basic pH.
Claim 167
Dependent Claim
55 words
154 . A two-component kit for producing a tissue adhesive or sealant comprising: (a) a first sealant component at an acid pH; (b) a second sealant component at a basic pH; and, (c) a cross-linker preparation that is active at an intermediate pH, wherein the cross-linker is activated upon mixing of (a), (b), and (c).
Claim 168
Dependent Claim
55 words
154 . A two-component kit for producing a tissue adhesive or sealant comprising: (a) a first sealant component at an acid pH; (b) a second sealant component at a basic pH; and, (c) a cross-linker preparation that is active at an intermediate pH, wherein the cross-linker is activated upon mixing of (a), (b), and (c).
Claim 169
Dependent Claim
22 words
155 . The kit of claim 153 , wherein the pH of said first protein preparation is between about 3.0 and 6.0.
Claim 170
Dependent Claim
22 words
156 . The kit of claim 153 , wherein the pH of said second protein preparation is between about 6.5 and 10.0.
Claim 171
Dependent Claim
32 words
157 . The kit of claim 152 , wherein said first protein preparation and said second protein preparation are selected from the group consisting of albumin, collagen, gelatin, globulins, protamine, and histones.
Claim 172
Dependent Claim
28 words
158 . The kit of claim 157 , wherein said first protein preparation and said second protein preparation comprise between about 3% (w/w) and about 50%(w/w) of protein.
Claim 173
Dependent Claim
29 words
159 . The kit of claim 157 , wherein said first protein preparation and said second protein preparation comprise albumin at between about 15% (w/w) and about 50% (w/w).
Claim 174
Dependent Claim
31 words
160 . A kit for producing a protein-based tissue adhesive or sealant comprising: (a) a preparation comprising a protein and a carbohydrate; (b) a degradation agent; and, (c) a cross-linker preparation.
Claim 175
Dependent Claim
31 words
160 . A kit for producing a protein-based tissue adhesive or sealant comprising: (a) a preparation comprising a protein and a carbohydrate; (b) a degradation agent; and, (c) a cross-linker preparation.
Claim 176
Dependent Claim
26 words
161 . The kit of claim 160 , wherein said protein is selected from the the group consisting of albumin, collagen, gelatin, globulins, protamine, and histones.
Claim 177
Dependent Claim
22 words
162 . The kit of claim 160 , wherein said protein is at a concentration of between about 15% and about 40%.
Claim 178
Dependent Claim
24 words
163 . The kit of claim 160 , wherein said carbohydrate is selected from the group consisting of natural and synthetic poly- and oligo-saccharides.
Claim 179
Dependent Claim
31 words
164 . The kit of claim 160 , wherein said carbohydrate is selected from the group consisting of of amylose, amylopectin, alginate, agarose, cellulose, carboxymethylcellulose, carboxymethylamylose, chitin, chitosan, pectin, and dextran.
Claim 180
Dependent Claim
25 words
165 . The kit of claim 160 , wherein said carbohydrate is at a concentration of between about about 0.1% (w/w) and about 10% (w/w).
Claim 181
Dependent Claim
22 words
166 . The kit of claim 160 , wherein said degradation agent is selected from the group consisting of proteases and glucanases.
Claim 182
Dependent Claim
14 words
167 . The kit of claim 166 , wherein said glucanases is an alginase.
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