FORMULATIONS FOR NONSURGICAL EXOGENOUS CROSSLINK THERAPY
First Claim
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1. A method of inducing methylglyoxal (MG)-mediated cross-linking in a native tissue having naturally-occurring collagen crosslinks within a living human body comprising contacting said tissue with MG at 5-50 mM and any combination of the following in a composition of about pH 8.0-9.5:
- (a) 4-(2-Hydroxyethyl)-1-piperazinepropanesulfonic acid (EPPS) buffer at 50-250 mM;
(b) 50-500 mM phosphate ions;
(c) sodium borohydride at about 1-5 mM; and
/or(d) a surfactant.
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Abstract
Improved methods and compositions for the treatment of native tissues with crosslinkers are provided. The methods and compositions will find particular use in increasing resistance to tearing, fissuring, rupturing, and/or delamination.
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Citations
40 Claims
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1. A method of inducing methylglyoxal (MG)-mediated cross-linking in a native tissue having naturally-occurring collagen crosslinks within a living human body comprising contacting said tissue with MG at 5-50 mM and any combination of the following in a composition of about pH 8.0-9.5:
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(a) 4-(2-Hydroxyethyl)-1-piperazinepropanesulfonic acid (EPPS) buffer at 50-250 mM; (b) 50-500 mM phosphate ions; (c) sodium borohydride at about 1-5 mM; and
/or(d) a surfactant. - View Dependent Claims (2, 3, 4)
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5-8. -8. (canceled)
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9. A method of inducing proanthrocyanidin (PA)-mediated cross-linking in a native tissue having naturally-occurring collagen crosslinks within a living human body comprising contacting said tissue with about 0.025-0.5% w/v PA and any combination of the following in a composition of about pH 5-9.5:
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(a) 50-25 mM Tris buffer; and
/or(b) a surfactant. - View Dependent Claims (10, 11, 12)
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13. A method of inducing transglutaminase (TG)-mediated cross-linking in a native tissue having naturally-occurring collagen crosslinks within a living human body comprising contacting said tissue with a composition comprising about 0.5-5 U/ml TG and any combination of the following at about pH 7-8:
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(a) 50-250 mM tris buffer; and
/or(b) a surfactant. - View Dependent Claims (14, 15, 16)
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17. A method of inducing 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide (EDC)-mediated cross-linking in a native tissue having naturally-occurring collagen cross-links within a living human body comprising contacting said tissue with about 2-10 mM EDC and any combination of the following in a composition of about pH 6.0:
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(a) 50-150 mM; and
/or(b) a surfactant. - View Dependent Claims (18, 19, 20, 21)
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22-25. -25. (canceled)
- 26. A method of inducing cross-linking in a native tissue having naturally-occurring collagen crosslinks within a living human body comprising contacting said tissue with a cross-linking agent and an anionic surfactant.
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31. A composition of matter comprising about 5-50 mM methylglyoxal (MG) and about 50-250 mM EPPS at about pH 8.0-9.5 and 50-500 mM phosphate ions.
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32. (canceled)
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33. A composition of matter comprising about 0.025-0.5% w/v of proanthrocyanidin (PA) and about 50-250 mM Tris at about pH 8.0-9.5.
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34. A composition of matter comprising about 20-100 mM L- or D-threose (LT or DT) and about 50-250 mM EPPS at about pH 8.0-9.5 and phosphate ions at about 50-500 mM.
- 35. A method of inducing cross-linking in a native tissue having naturally-occurring collagen crosslinks within a living human body comprising contacting said tissue with any combination of methylglyoxal at 5-50 mM, genipin at about 20 mM or less, about 0.025-0.5% w/v proanthrocyanidin, about 0.5-5 U/ml transglutaminase, 2-10 mM 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide (EDC), 20-100 mM L- or D-threose.
Specification