Wound healing compositions

Abstract

Provided herein are biologically active solution compositions comprising one or more sacrificial proteolytic enzyme substrates, one or more preservatives, and one or more antimicrobial agents and methods of using the solution compositions to treat tissue sites, in particular chronic wounds. The compositions may be used in conjunction with negative pressure wound therapy to treat tissue sites.

We claim: 
     
         1 . A pharmaceutical composition for use in a method of wound healing, wherein the pharmaceutical composition is configured to be administered to a tissue site by fluid instillation therapy in the form of a solution, wherein the composition comprises:
 one or more matrix metalloprotease (MMP) substrates comprising gelatin or a hydrolysate thereof;   one or more preservatives selected from the group consisting of ethylenediaminetetraacetic acid (EDTA), diethylene triamine pentaacetic acid (DTPA), catechins, sodium benzoate, potassium sorbate, and sodium nitrate;   one or more antimicrobial agents; and   a pharmaceutically acceptable carrier.   
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the antimicrobial agent is selected from the group consisting of aloe vera components, ashitaba, bacteriophage, beta-defensin, quaternary ammonium compound, chlorhexidine, copper, dispersin B, essential oil, gentamicin, lactoferrin, lysostaphin N-halamines, nitric oxide, oleic acid, PLUNC protein, polyhexanide biguanide (PHIVIB), bacteriocin, selenium, silver compound, triclosan, zinc, and combinations thereof. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the quaternary ammonium compound is benzethonium chloride or benzalkonium chloride. 
     
     
         4 . The pharmaceutical composition of  claim 2 , wherein the beta-defensin is cathelicidin (LL-37). 
     
     
         5 . The pharmaceutical composition of  claim 2 , wherein the silver compound is colloidal silver, ionic silver, silver chloride, silver nanopartices, or silver sulfadiazine. 
     
     
         6 . The pharmaceutical composition of  claim 2 , wherein the essential oil is cinnamon oil, clove oil, eucalyptus oil, or tea tree oil. 
     
     
         7 . The pharmaceutical composition of  claim 2 , wherein the chlorhexidine is chlorhexidine gluconate. 
     
     
         8 . The pharmaceutical composition of  claim 1 , further comprising one or more growth factors. 
     
     
         9 . The pharmaceutical composition of  claim 1 , further comprising one or more proteinase inhibitors that are proteinase inhibitors of MMPs. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the gelatin comprises a molecular weight of between 2000 Da to 20,000 Da. 
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein the gelatin has a bloom value of less than 150. 
     
     
         12 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition comprises 0.1% to 25% w/w gelatin. 
     
     
         13 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition comprises 1% to 10% w/w gelatin. 
     
     
         14 . A kit comprising a container and a composition within the container, the composition comprising:
 one or more matrix metalloprotease (MMP) substrates, wherein the MMP substrates comprise gelatin or a hydrolysate thereof,   one or more preservatives comprising a chelating agent, wherein the chelating agent is ethylenediaminetetraacetic acid (EDTA), and   a pharmaceutically-acceptable carrier;   wherein the composition is provided in a dispensable liquid form for instillation to a tissue site.   
     
     
         15 . The kit of  claim 14 , further comprising a dressing having a first portion adapted for contact with the tissue site and a second portion in fluid communication with the container. 
     
     
         16 . The kit of  claim 15 , wherein the dressing comprises an open-cell reticulated polyurethane foam pad. 
     
     
         17 . The kit of  claim 16 , wherein the foam pad is treated with the composition prior to use. 
     
     
         18 . The kit of  claim 16 , wherein the foam pad is infused and coated on the surface with the composition. 
     
     
         19 . The kit of  claim 14 , wherein the composition further comprises one or more antimicrobial agents. 
     
     
         20 . The kit of  claim 14 , wherein the composition further comprises one or more growth factors.