Method for suppressing or preventing fibrous adhesion formation using a multicomponent aqueous oxychlorine composition prepared on-site

Abstract

A composition and method are described for suppressing or preventing fibrous adhesion formation using a multicomponent aqueous oxychlorine composition. Fibrous adhesions typically form during healing of tissue, for example following a surgical procedure. A multicomponent oxychlorine composition is provided for irrigating the tissue which minimizes post-surgical adhesion formation, the composition containing both chlorine dioxide and chlorite ion, and a complex ion thereof. The chlorine dioxide level generally is in an effective range of ClO 2 concentration from about 10 ppm to a maximum of about 110 ppm. In a preferred embodiment, a physiological composition is provided in a thickened form to increase retention in the area being treated. The composition is preferably based on a standard saline solution converted to the oxychlorine composition just prior to use by sequential addition of aqueous concentrates of a chlorite salt, a hypochlorite salt combined with a physiological buffer-producing salt of a multibasic acid, and an acidifying agent, optionally including a thickening agent.

1 . A method for suppressing or reducing the likelihood of the development of fibrous adhesions in tissue of a mammal after surgical intervention comprising treating the tissue with an effective amount of a composition prepared on site of said surgical intervention comprising a multiple oxychlorine species-containing a buffered, isotonic composition. 
     
     
         2 . The method of  claim 1  wherein the composition is based on a standard saline solution, and the multiple oxychlorine species comprise at least chlorine dioxide and a chlorite ion, with the exception of hypochlorite. 
     
     
         3 . The method of  claim 1  wherein the multiple oxychlorine species com p rise at least chlorine dioxide and hypochlorous acid and/or hypochlorite ion, with the exception of chlorite. 
     
     
         4 . The method of  claim 1  further comprising, immediately before treating the tissue, preparing the composition by controllably combining an initial alkali- or alkaline-metal chlorite salt and alkali- or alkaline-metal hypochlorite salt reactants in a molar ratio of the initial alkali- or alkaline-metal chlorite salt to the alkali- or alkaline-metal hypochlorite salt reactants such that residual chlorite ion remains in solution after a portion has been oxidized to form chlorine dioxide. 
     
     
         5 - 11 . (canceled) 
     
     
         12 . The method of  claim 4  wherein a molar ratio of formed chlorine dioxide to residual chlorite ion is equal to or less than about 3.5 to 1. 
     
     
         13 . The method of  claim 2  wherein the composition has a level of chlorine dioxide in the range from about 10 parts per million (ppm) to about 110 ppm. 
     
     
         14 . The method of  claim 4  wherein the initial alkaline chlorite salt and alkaline hypochlorite salt reactants are sodium chlorite and sodium hypochlorite. 
     
     
         15 . The method of  claim 4  wherein the initial alkaline chlorite salt has a chlorite anion concentration in the range from about 20 mg per liter to about 200 mg per liter. 
     
     
         16 . The method of  claim 15  further comprising providing the initial sodium hypochlorite salt at a concentration in the range of from about 6 mg per liter to about 60 mg per liter, the concentration being proportionate to a concentration of the chlorite which is less than an amount of hypochorite required to effect complete oxidation to chlorine dioxide. 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 3  further comprising providing a molar ratio such that residual hypochlorite and/or hypochlorous acid remain in solution after the chlorite salt has been fully consumed. 
     
     
         19 . The method of  claim 18  wherein the molar ratio of initial alkali- or alkaline-earth hypochlorite salt with respect to the initial alkali- or alkaline-earth chlorite salt provides about a 10% to about a 50% molar excess with respect to an amount required for oxidation of the chlorite to chlorine dioxide. 
     
     
         20 . The method of  claim 19  wherein the about 10% to about 50% molar excess corresponds to about 18 mg per liter to about 25 mg per liter, for systems that create about 10 ppm of chlorine dioxide, to about 200 to about 270 mg per liter for systems that create about 110 ppm of chlorine dioxide. 
     
     
         21 . The method of  claim 1  wherein the composition is in the form of a viscous liquid. 
     
     
         22 . The method of  claim 21  wherein the viscous liquid has viscosity in a range of from about 50 cps to about 2,500 cps. 
     
     
         23 . The method of  claim 21  wherein the composition contains a thickening agent selected from the group consisting of xanthan gum, methylcellulose, hydroxyethylcellulose, methylhydroxypropylcellulose, methylhydroxyethylcellulose and combinations thereof. 
     
     
         24 - 26 . (canceled) 
     
     
         27 . The method of  claim 1  wherein the treating of the tissue comprises perfusing a surface wound to suppress scar and keloid formation. 
     
     
         28 . The method of  claim 1  wherein the treating of the tissue comprises bathing ocular surfaces. 
     
     
         29 . The method of  claim 1  wherein the treating of the tissue comprises applying the composition to suppress or prevent symblepharon, the adhesions between palpebral conjunctivae of the eyelid and bulbar conjunctivae of the eye ball or following a pneumothorax to suppress pleural adhesion formation, or to suppress intrauterine synechiae produced by a myomectomy or mechanical abortion. 
     
     
         30 . The method of  claim 1  wherein the treating of the tissue comprises applying the composition during optic surgery. 
     
     
         31 . A method for suppressing or preventing development of fibrous adhesions resulting from a surgical procedure performed on a surgical site comprising treating the surgical site with an effective amount of a composition comprising a multiple oxychlorine species-containing buffered, isotonic composition. 
     
     
         32 . The method of  claim 31  wherein the surgical procedure involves an incision of the peritoneal cavity for correction of pathological conditions including, but not limited, to corrective surgery, puncture and tear wounds, burst appendices, for suppressing or eliminating formation of post-surgical internal fibrous adhesions. 
     
     
         33 . The method of  claim 31  wherein the surgical procedure is undertaken to correct pre-existing adhesions, by severing the adhesion to create a surgical site and treating the surgical site to suppress reformation. 
     
     
         34 . The method of  claim 31  wherein the surgical procedure is a laminectomy. 
     
     
         35 . (canceled) 
     
     
         36 . The method of  claim 31  further comprising adding a thickening agent to provide the composition with a viscosity of from about 50 cps to about 2,500 cps to prolong retention at the surgical site. 
     
     
         37 . The method of  claim 31  wherein the surgical site is a topical site and treating the surgical site comprises perfusing the topical site. 
     
     
         38 - 48 . (canceled)