US2016250377A1PendingUtilityA1

Light activated composite tissue adhesives

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Individually held — no corporate assignee on recordPriority: Nov 10, 2009Filed: Mar 13, 2015Published: Sep 1, 2016
Est. expiryNov 10, 2029(~3.3 yrs left)· nominal 20-yr term from priority
Inventors:Barbara A. SoltzRobert Soltz
A61P 43/00A61L 24/102A61K 47/42A61K 9/7007A61B 2017/00951A61K 38/39A61P 17/02A61B 2017/00004A61B 2017/00517A61L 2300/428A61K 31/525A61B 17/00491A61B 2017/005A61L 31/14A61L 24/0015A61L 31/044A61B 2017/00884
38
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Claims

Abstract

A light activated collagen-flavin composite layer incorporating riboflavin is applied as treatment for infected lesions. These composites have also been found to be strong tissue adhesives that are effective in closing and sealing wounds, fixation of grafts/ implants and anastomoses. Advantages include speed of closure, reduced infection due to the elimination of foreign matter, evidence of accelerated wound healing and the ease of use in complex surgery, especially when watertight seals, limited access or small repair size are important factors. The riboflavin in the collagen layer is exposed to light (e.g., light having a wavelength between 360-375 nm or 440-480 nm), decomposing the riboflavin to form reactive oxygen species (ROS). Strong crosslinks between the collagen composite and tissue results. In addition, similar exposures eradicate pathogens in the wound.

Claims

exact text as granted — not AI-modified
1 - 43 . (canceled) 
     
     
         44 . A composition, comprising:
 collagen, wherein the concentration of the collagen in the composition is from 300 mg/ml up to and including 800 mg/ml, and wherein the collagen being derivatized with a COO −  functional group; and riboflavin, wherein a concentration of the riboflavin is 0.1% (w/v) to a concentration substantially equal to 1.0% (w/v).   
     
     
         45 . A composition in accordance with  claim 44 , wherein the concentration of the riboflavin in the composition is substantially equal to 1.0% (w/v). 
     
     
         46 . A composition comprising;
 collagen, wherein the concentration of the collagen in the composition is from 300 mg/ml up to and including 800 mg/ml; and   a chromophore that produces a reactive oxygen species upon exposure to electromagnetic radiation, wherein the concentration of the chromophore is 0.1% (w/v) to a concentration substantially equal to 1.0% (w/v), and wherein the chromophore is selected from the group consisting of: riboflavin, luminflavin, and lumichrome.   
     
     
         47 . A composition in accordance with  claim 46 , wherein the chromophore includes riboflavin. 
     
     
         48 . A composition in accordance with  claim 46 , wherein the concentration of the riboflavin in the composition is substantially equal to 1.0% (w/v). 
     
     
         49 . A composition in accordance with  claim 46 , wherein the chromophore is luminflavin. 
     
     
         50 . A composition in accordance with  claim 46 , wherein the chromophore is lumichrome. 
     
     
         51 . A composition in accordance with  claim 46 , wherein the collagen is gelatinized. 
     
     
         52 . A composition in accordance with  claim 46 , wherein at least a portion of the collagen is derivatized with a COO −  functional group. 
     
     
         53 . A composition in accordance with  claim 46 , wherein the electromagnetic radiation has a wavelength in a range of 360 nm to 375 nm. 
     
     
         54 . A composition in accordance with  claim 46 , wherein the electromagnetic radiation has a wave length in a range of 440 nm to 480 nm. 
     
     
         55 . A composition in accordance with  claim 54 , wherein the wavelength is substantially equal to 450 nm. 
     
     
         56 . A method, comprising:
 applying a composition in accordance with  claim 46  to a tissue, and exposing the composition to optical energy having a wavelength in a range of 440-480 nm.   
     
     
         57 . A method in accordance with  claim 56 , wherein the chromophore is riboflavin. 
     
     
         58 . A method in accordance with  claim 56 , wherein the concentration of the riboflavin in the composition is substantially equal to 1.0% (w/v). 
     
     
         59 . A method in accordance with  claim 56 , wherein the chromophore is lumiflavin. 
     
     
         60 . A method in accordance with  claim 56 , wherein the chromophore is lumichrome. 
     
     
         61 . A method in accordance with  claim 56 , wherein the collagen is gelatinized. 
     
     
         62 . A method in accordance with  claim 56 , wherein at least a portion of the collagen is derivatized with a COO −  functional group. 
     
     
         63 . A method in accordance with  claim 56 , wherein the wavelength is substantially equal to 450 nm. 
     
     
         64 . A method in accordance with  claim 56 , wherein an intensity of the optical energy in the collagen layer is in a range of 0.1 W/cm 2 -2.0 W/cm 2 . 
     
     
         65 . A method in accordance with  claim 56 , wherein the tissue includes a human tissue lesion or wound. 
     
     
         66 . A method in accordance with  claim 56 , wherein said exposure is for a duration of 5 min-30 min. 
     
     
         67 . A composition, comprising:
 a first layer including:   a first collagen, wherein the concentration of the first collagen in the first layer is from 300 mg/ml up to and including 800 mg/ml, and   a first chromophore that produces a reactive oxygen species upon exposure to electromagnetic radiation, the first layer having been exposed to electromagnetic radiation having a wavelength in a range of 360-375 nm or 440-480 nm, wherein the concentration of the first chromophore is 0.1% (w/v) to a concentration substantially equal to 1.0% (w/v), and wherein the first chromophore is selected from the group consisting of: riboflavin, luminflavin, and lumichrome; and   a second layer including:   a second collagen, wherein the concentration of the second collagen in the second layer is from 300 mg/ml up to and including 800 mg/ml, and   a second chromophore that produces a reactive oxygen species upon exposure to electromagnetic radiation.   
     
     
         68 . A composition in accordance with  claim 67 , wherein the first and second chromophore is riboflavin. 
     
     
         69 . A composition in accordance with  claim 67 , wherein the first and second chromophore is lumiflavin. 
     
     
         70 . A composition in accordance with  claim 67 , wherein the first and second chromophore is lumichrome. 
     
     
         71 . A composition in accordance with  claim 67 , wherein the first and second collagen is derivatized with a COO −  functional group. 
     
     
         72 . A composition in accordance with  claim 44 , wherein the concentration of the collagen in the composition is from 300 mg/ml up to and including 600 mg/ml, the collagen being derivatized with a COO −  functional group. 
     
     
         73 . A composition in accordance with  claim 46 , wherein the concentration of the collagen in the composition is from 300 mg/ml up to and including 600 mg/ml, the collagen being derivatized with a COO −  functional group.

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