US6015474A
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US
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Methods of using primer molecules for enhancing the mechanical performance of tissue adhesives and sealants
Assignee: Protein Polymer Technologies Inc
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Filing: 1997-06-20
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Granted: 2000-01-18
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Expires: 2017-06-20
Abstract
Abstract The present invention concerns novel methods for enhancing the mechanical performance of tissue adhesives and sealants which comprises employing a primer molecule in association with a tissue adhesive or sealant, wherein the primer molecule serves to enhance the strength of the interface between the tissue and the adhesive matrix. The primer molecules described herein function to interact with collagen present in the tissue, thereby altering its characteristics to make it more amenable to bonding with the adhesive matrix. Primer molecules may be applied to the tissue independently from the tissue adhesive or sealant or may be mixed with the tissue adhesive or sealant prior to application to the tissue.
Inventors
- 👤 Erwin R. Stedronsky
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 13:10
CPC Classifications
A; A61; A61L; A61L24/00; A61L24/001; A61L24/04; A61L24/10; A61L24/106; Y; Y10; Y10T; Y10T428/00; Y10T428/28; Y10T428/2852; Y10T428/2865; Y10T428/31504; Y10T428/31536; Y10T428/31725; Y10T428/3175; Y10T428/31754
Claims Analysis
Total Claims: 36
Claim 1
Independent Claim
105 words
A method of maintaining separated tissue in proximate relationship, said method comprising: applying to said separated tissue (a) a primer molecule, wherein said primer molecule is urea, a suiphonated aromatic compound, a protein or an oglioreptide and (b) a tissue adhesive comprising a natural or recombinantly-produced protein, said primer molecule being capable of physically interacting with collagen present in said separated tissue and thereby rendering said separated tissue capable of forming a bonded interface with said tissue adhesive, wherein (a) and (b) are applied in an amount effective to maintain said separated tissue in proximate relationship when said separated tissue is brought into proximate relationship.
Claim 2
Independent Claim
105 words
A method of maintaining separated tissue in proximate relationship, said method comprising: applying to said separated tissue (a) a primer molecule, wherein said primer molecule is urea, a suiphonated aromatic compound, a protein or an oglioreptide and (b) a tissue adhesive comprising a natural or recombinantly-produced protein, said primer molecule being capable of physically interacting with collagen present in said separated tissue and thereby rendering said separated tissue capable of forming a bonded interface with said tissue adhesive, wherein (a) and (b) are applied in an amount effective to maintain said separated tissue in proximate relationship when said separated tissue is brought into proximate relationship.
Claim 3
Dependent Claim
32 words
The method according to claim 1 which maintains said separated tissue in proximate relationship with greater bond strength than when said tissue adhesive is employed in the absence of said primer molecule.
Claim 4
Dependent Claim
26 words
The method according to claim 1, wherein said primer molecule is applied to said separated tissue before said tissue adhesive is applied to said separated tissue.
Claim 5
Dependent Claim
23 words
The method according to claim 1, wherein said tissue adhesive and said primer molecule are combined prior to application to said separated tissue.
Claim 6
Dependent Claim
19 words
The method according to claim 1, wherein said applying occurs prior to bringing said separated tissue into proximate relationship.
Claim 7
Dependent Claim
18 words
The method according to claim 1, wherein said applying occurs after bringing said separated tissue into proximate relationship.
Claim 8
Dependent Claim
12 words
The method according to claim 1, wherein said primer molecule is urea.
Claim 9
Dependent Claim
15 words
The method according to claim 1, wherein said primer molecule is a sulfonated aromatic compound.
Claim 10
Dependent Claim
83 words
The method according to claim 8, wherein said sulfonated aromatic compound is selected from the group consisting of Brilliant Blue G (Aldrich 23.464-8), Evan's Blue (Aldrich 20,633-4), Chicago Sky Blue 6B (Aldrich 20,138-3), Cibacron Blue 3GA (Sigma C9534), Cibacron Brilliant Yellow 3G-P (Aldrich 22,847-8), Brilliant Blue R (Aldrich 20,140-5), Lissamine Green B (Aldrich 19,958-3), Acid Blue 92 (Aldrich 21,042-0), Cibacron Brilliant Red 3B-A (Aldrich 22,845-1), Acid Red 97 (Aldrich 21,039-0), Trypan Blue (Aldrich 30,264-3), New Coccine (Aldrich 19,973-7) and Orange G (Aldrich 86,128-6).
Claim 11
Dependent Claim
17 words
The method according to claim 8, wherein said sulfonated aromatic compound is Brilliant Blue G (Aldrich 23.464-8).
Claim 12
Dependent Claim
13 words
The method according to claim 1, wherein said primer molecule is a protein.
Claim 13
Dependent Claim
20 words
The method according to claim 11, wherein said protein is selected from the group consisting of fibrinogen, SELP8K and SELP0K-CS1.
Claim 14
Dependent Claim
13 words
The method according to claim 1, wherein said primer molecule is an oligopeptide.
Claim 15
Independent Claim
91 words
A method of sealing a defect in tissue, said method comprising; applying to said defect (a) a primer molecule, wherein said primer molecule is urea, a sulphonated aromatic compound, a protein or an oligopeptide and (b) a tissue sealant comprising a natural or recombinantly-produced protein, said primer molecule being capable of physically interacting with collagen present in said tissue and thereby rendering said tissue capable of forming a bonded interface with said tissue sealant, wherein (a) and (b) are applied to said defect in an amount effective to seal said defect.
Claim 16
Independent Claim
91 words
A method of sealing a defect in tissue, said method comprising; applying to said defect (a) a primer molecule, wherein said primer molecule is urea, a sulphonated aromatic compound, a protein or an oligopeptide and (b) a tissue sealant comprising a natural or recombinantly-produced protein, said primer molecule being capable of physically interacting with collagen present in said tissue and thereby rendering said tissue capable of forming a bonded interface with said tissue sealant, wherein (a) and (b) are applied to said defect in an amount effective to seal said defect.
Claim 17
Dependent Claim
24 words
The method according to claim 14, wherein said primer molecule is applied to said defect before said tissue sealant is applied to said defect.
Claim 18
Dependent Claim
22 words
The method according to claim 14, wherein said tissue sealant and said primer molecule are combined prior to application to said defect.
Claim 19
Dependent Claim
16 words
The method according to claim 14, wherein said defect is a result of a surgical procedure.
Claim 20
Dependent Claim
90 words
A composition of matter usefull for forming a bonded interface with a tissue when said composition of matter is applied to said tissue, said composition of matter comprising: (a) a tissue adhesive or sealant which comprises a natural or recombinantly-produced protein; and (b) a primer molecule which is capable of physically interacting with collagen present in said tissue and thereby rendering said tissue capable of for a bonded interface with said tissue adhesive or sealant and wherein said primner molecules urea, a sulphonated aromatic compound, a protein or an oligopeptide.
Claim 21
Dependent Claim
90 words
A composition of matter usefull for forming a bonded interface with a tissue when said composition of matter is applied to said tissue, said composition of matter comprising: (a) a tissue adhesive or sealant which comprises a natural or recombinantly-produced protein; and (b) a primer molecule which is capable of physically interacting with collagen present in said tissue and thereby rendering said tissue capable of for a bonded interface with said tissue adhesive or sealant and wherein said primner molecules urea, a sulphonated aromatic compound, a protein or an oligopeptide.
Claim 22
Dependent Claim
11 words
A kit comprising the composition of matter according to claim 18.
Claim 23
Dependent Claim
12 words
The method according to claim 14, wherein said primer molecule is urea.
Claim 24
Dependent Claim
15 words
The method according to claim 14, wherein said primer molecule is a sulphonated aromatic compound.
Claim 25
Dependent Claim
83 words
The method according to claim 21, wherein said sulfonated aromatic compound is selected from the group consisting of Brilliant Blue G (Aldrich 23,464-8), Evan's Blue (Aldrich 20,633-4), Chicago Sky Blue 6B (Aldrich 20,138-3), Cibacron Blue 3GA (Sigma C9534), Cibacron Brilliant Yellow 3G-P (Aldrich 22,847-8), Brilliant Blue R (Aldrich 20,140-5), Lissamine Green B (Aldrich 19,958-3), Acid Blue 92 (Aldrich 21,042-0), Cibacron Brilliant Red 3B-A (Aldrich 22,845-1), Acid Red 97 (Aldrich 21,039-0), Trypan Blue (Aldrich 30,264-3), New Coccine (Aldrich 19,973-7) and Orange G (Aldrich 86,128-6).
Claim 26
Dependent Claim
17 words
The method according to claim 21, wherein said sulfonated aromatic compound is Brilliant Blue G (Aldrich 23,464-8).
Claim 27
Dependent Claim
13 words
The method according to claim 14, wherein said primer molecule is a protein.
Claim 28
Dependent Claim
20 words
The method according to claim 24, wherein said protein is selected from the group consisting of fibrinogen, SELP8K and SELP0K-CS1.
Claim 29
Dependent Claim
13 words
The method according to claim 14, wherein said primer molecule is an oligopeptide.
Claim 30
Independent Claim
190 words
A method of maintaining separated tissue in proximate relationship, said method comprising: applying to said separated tissue (a) a primer molecule and (b) a tissue adhesive, said primer molecule being capable of physically interacting with collagen present in said separated tissue and thereby rendering said separated tissue capable of forming a bonded interface with said tissue adhesive, wherein (a) and (b) are applied in an amount effective to maintain said separated tissue in proximate relationship when said separated tissue is brought into proximate relationship and wherein said primer molecule is selected from the group consisting of Brilliant Blue G (Aldrich 23,464-8), Evan's Blue (Aldrich 20,633-4), Chicago Sky Blue 6B (Aldrich 20,138-3), Cibacron Blue 3GA (Sigma C9534); Cibacron Brilliant Yellow 3G-P (Aldrich 22,847-8), Brilliant Blue R (Aldrich 20,140-5), Lissamine Green B (Aldrich 19,958-3), Acid Blue 92 (Aldrich 21,042-0), Cibacron Brilliant Red 3B-A (Aldrich 22,845-1), Acid Red 97 (Aldrich 21,039-0), Trypan Blue (Aldrich 30,264-3), New Coccine (Aldrich 19,973-7), Orange G (Aldrich 86,128-6), Hydroxy Napthol Blue di-sodium salt (Aldrich 21,991-6), Ponceau S (Aldrich 14,119-4), Bordeaux R (Aldrich 20,962-7), Aniline Blue (Aldrich 41,504-9), Reactive Black 5 (Aldrich 30,645-2), fibrinogen, fibronectin, albumin, SELP0K and SELP0K-CS1.
Claim 31
Independent Claim
190 words
A method of maintaining separated tissue in proximate relationship, said method comprising: applying to said separated tissue (a) a primer molecule and (b) a tissue adhesive, said primer molecule being capable of physically interacting with collagen present in said separated tissue and thereby rendering said separated tissue capable of forming a bonded interface with said tissue adhesive, wherein (a) and (b) are applied in an amount effective to maintain said separated tissue in proximate relationship when said separated tissue is brought into proximate relationship and wherein said primer molecule is selected from the group consisting of Brilliant Blue G (Aldrich 23,464-8), Evan's Blue (Aldrich 20,633-4), Chicago Sky Blue 6B (Aldrich 20,138-3), Cibacron Blue 3GA (Sigma C9534); Cibacron Brilliant Yellow 3G-P (Aldrich 22,847-8), Brilliant Blue R (Aldrich 20,140-5), Lissamine Green B (Aldrich 19,958-3), Acid Blue 92 (Aldrich 21,042-0), Cibacron Brilliant Red 3B-A (Aldrich 22,845-1), Acid Red 97 (Aldrich 21,039-0), Trypan Blue (Aldrich 30,264-3), New Coccine (Aldrich 19,973-7), Orange G (Aldrich 86,128-6), Hydroxy Napthol Blue di-sodium salt (Aldrich 21,991-6), Ponceau S (Aldrich 14,119-4), Bordeaux R (Aldrich 20,962-7), Aniline Blue (Aldrich 41,504-9), Reactive Black 5 (Aldrich 30,645-2), fibrinogen, fibronectin, albumin, SELP0K and SELP0K-CS1.
Claim 32
Independent Claim
176 words
A method of sealing a defect in tissue, said method comprising: applying to said defect (a) a primer molecule and (b) a tissue sealant, said primer molecule being capable of physically interacting with collagen present in said tissue and thereby rendering said tissue capable of forming a bonded interface with said tissue sealant, wherein (a) and (b) are applied to said defect in an amount effective to seal said defect and wherein said primer molecule is selected from the group consisting of Brilliant Blue G (Aldrich 23,464-8), Evan's Blue (Aldrich 20,633-4), Chicago Sky Blue 6B (Aldrich 20,138-3), Cibacron Blue 3GA (Sigma C9534), Cibacron Brilliant Yellow 3G-P (Aldrich 22,847-8), Brilliant Blue R (Aldrich 20,140-5), Lissamine Green B (Aldrich 19,958-3), Acid Blue 92 (Aldrich 21,042-0), Cibacron Brilliant Red 3B-A (Aldrich 22,845-1), Acid Red 97 (Aldrich 21,039-0), Trypan Blue (Aldrich 30,264-3), New Coccine (Aldrich 19,973-7), Orange G (Aldrich 86,128-6), Hydroxy Napthol Blue di-sodium salt (Aldrich 21,991-6), Ponceau S (Aldrich 14,119-4), Bordeaux R (Aldrich 20,962-7), Aniline Blue (Aldrich 41,504-9), Reactive Black 5 (Aldrich 30,645-2), fibrinogen, fibronectin, albumin, SELP0K and SELP0K-CS1.
Claim 33
Independent Claim
176 words
A method of sealing a defect in tissue, said method comprising: applying to said defect (a) a primer molecule and (b) a tissue sealant, said primer molecule being capable of physically interacting with collagen present in said tissue and thereby rendering said tissue capable of forming a bonded interface with said tissue sealant, wherein (a) and (b) are applied to said defect in an amount effective to seal said defect and wherein said primer molecule is selected from the group consisting of Brilliant Blue G (Aldrich 23,464-8), Evan's Blue (Aldrich 20,633-4), Chicago Sky Blue 6B (Aldrich 20,138-3), Cibacron Blue 3GA (Sigma C9534), Cibacron Brilliant Yellow 3G-P (Aldrich 22,847-8), Brilliant Blue R (Aldrich 20,140-5), Lissamine Green B (Aldrich 19,958-3), Acid Blue 92 (Aldrich 21,042-0), Cibacron Brilliant Red 3B-A (Aldrich 22,845-1), Acid Red 97 (Aldrich 21,039-0), Trypan Blue (Aldrich 30,264-3), New Coccine (Aldrich 19,973-7), Orange G (Aldrich 86,128-6), Hydroxy Napthol Blue di-sodium salt (Aldrich 21,991-6), Ponceau S (Aldrich 14,119-4), Bordeaux R (Aldrich 20,962-7), Aniline Blue (Aldrich 41,504-9), Reactive Black 5 (Aldrich 30,645-2), fibrinogen, fibronectin, albumin, SELP0K and SELP0K-CS1.
Claim 34
Dependent Claim
173 words
A composition of matter useful for forming a bonded interface with a tissue when said composition of matter is applied to said tissue, said composition of matter comprising: (a) a tissue adhesive or sealant; and (b) a primer molecule which is capable of physically interacting with collagen present in said tissue and thereby rendering said tissue capable of forming a bonded interface with said tissue adhesive or sealant, wherein said primer molecule is selected from the group consisting of Brilliant Blue G (Aldrich 23,464-8), Evan's Blue (Aldrich 20,633-4), Chicago Sky Blue 6B (Aldrich 20,138-3), Cibacron Blue 3GA (Sigma C9534), Cibacron Brilliant Yellow 3G-P (Aldrich 22,847-8), Brilliant Blue R (Aldrich 20,140-5), Lissamine Green B (Aldrich 19,958-3), Acid Blue 92 (Aldrich 21,042-0), Cibacron Brilliant Red 3B-A (Aldrich 22,845-1), Acid Red 97 (Aldrich 21,039-0), Trypan Blue (Aldrich 30,264-3), New Coccine (Aldrich 19,973-7), Orange G (Aldrich 86,128-6), Hydroxy Napthol Blue di-sodium salt (Aldrich 21,991-6), Ponceau S (Aldrich 14,119-4), Bordeaux R (Aldrich 20,962-7), Aniline Blue (Aldrich 41,504-9), Reactive Black 5 (Aldrich 30,645-2), fibrinogen, fibronectin, albumin, SELP0K and SELP0K-CS1.
Claim 35
Dependent Claim
173 words
A composition of matter useful for forming a bonded interface with a tissue when said composition of matter is applied to said tissue, said composition of matter comprising: (a) a tissue adhesive or sealant; and (b) a primer molecule which is capable of physically interacting with collagen present in said tissue and thereby rendering said tissue capable of forming a bonded interface with said tissue adhesive or sealant, wherein said primer molecule is selected from the group consisting of Brilliant Blue G (Aldrich 23,464-8), Evan's Blue (Aldrich 20,633-4), Chicago Sky Blue 6B (Aldrich 20,138-3), Cibacron Blue 3GA (Sigma C9534), Cibacron Brilliant Yellow 3G-P (Aldrich 22,847-8), Brilliant Blue R (Aldrich 20,140-5), Lissamine Green B (Aldrich 19,958-3), Acid Blue 92 (Aldrich 21,042-0), Cibacron Brilliant Red 3B-A (Aldrich 22,845-1), Acid Red 97 (Aldrich 21,039-0), Trypan Blue (Aldrich 30,264-3), New Coccine (Aldrich 19,973-7), Orange G (Aldrich 86,128-6), Hydroxy Napthol Blue di-sodium salt (Aldrich 21,991-6), Ponceau S (Aldrich 14,119-4), Bordeaux R (Aldrich 20,962-7), Aniline Blue (Aldrich 41,504-9), Reactive Black 5 (Aldrich 30,645-2), fibrinogen, fibronectin, albumin, SELP0K and SELP0K-CS1.
Claim 36
Dependent Claim
11 words
A kit comprising the composition of matter according to claim 29.
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