Abstract:
A method and composition for cleansing a wound comprising irrigating the wound with a surfactant, an antiseptic, and a preservative mixed in an aqueous solution having minimal cytotoxicity, and thereby cleansing the wound with minimal scarring.

Description:
FIELD OF THE INVENTION 
     The present invention relates to methods and compositions for cleansing wounds which promote optimal wound healing wherein the wound-cleansing compositions have minimal cytotoxicity. This application is a continuation-in-part of U.S. application Ser. No. 08/313,714 filed Sep. 27, 1994 now abandoned. 
    
    
     BACKGROUND OF THE INVENTION 
     Proper wound cleansing is an integral step in all wound treatment regimens. For treatment of minor cuts and abrasions, cleansing is most often effected with soap and water, hydrogen peroxide, or rubbing alcohol. While these cleansers may be effective in disinfecting the wound, they are biologically aggressive and result in destruction of tissue in the wound site. This destruction of tissue, referred to as cytotoxicity, hinders the wound healing process and often increases the degree of scarring which appears over the healed wound area. While it is essential to remove exogenous debris and potential pathogens from the wound site, the wound cleanser must be as non-cytotoxic as possible in order to promote the most favorable conditions for wound healing. 
     SUMMARY OF THE INVENTION 
     The present invention comprises methods and compositions for cleansing wounds with minimal scarring wherein said wound-cleansing compositions have minimal cytotoxicity and comprise a low-cytotoxic surfactant, a low-cytotoxic antiseptic, and a non-cytotoxic preservative, mixed in an aqueous solution. 
     In one embodiment of the present invention, the surfactant comprises a polyoxyethylene, polyoxypropylene block polymer. In another embodiment the antiseptic comprises benzalkonium chloride, benzethonium chloride, camphorated metacresol, camphorated phenol, hexylresorcinol, methylbenzethonium chloride, or phenol. In still another embodiment the preservative comprises sodium benzoate, glydant, (also referred to as DMDM hydantoin) potassium sorbate, chlorhexidine digluconate or a combination thereof. 
     DETAILED DESCRIPTION OF THE INVENTION 
     The present invention is directed to novel methods for cleansing wounds with minimal scarring and compositions for cleansing wounds with minimal scarring wherein the non-cytotoxic, wound-cleansing compositions comprise a surfactant, an antiseptic, and a preservative, and wherein said compositions are highly effective at promoting wound healing. The compositions of the present invention comprise topical solutions which are suitable for use in cleansing all types of wounds, particularly wounds associated with minor cuts and abrasions. The compositions are mixed in an aqueous solution to provide a minimally cytotoxic solution for cleansing wounds. 
     The non-cytotoxic surfactant used in the present invention removes exogenous debris such as dirt and grease from the wound via surface activity. The non-cytotoxic surface active agents tend to be nonionic surfactants, especially those that have high molecular weights such as the block copolymers. These surface active agents quickly migrate to the dirt or grease interface and lift the exogenous debris from the wound upon irrigation with the wound cleansing composition. The low-cytotoxic antiseptic destroys microbial and bacterial pathogens in the wound site, and the preservative agent prevents the growth of bacteria and fungi that might contaminate the unused portion of the product. A preservative must be present for a multiple use product container. 
     The surfactant used in the present invention may comprise a polyoxyethylene, polyoxypropylene block polymer which is commonly referred to as a &#34;Poloxamer&#34;. The preferred Poloxamer is polyoxyethylene or polyoxypropylene block polymer of ethylene diamine. The surfactant preferably comprises about 1 to about 20 weight percent of the total composition. 
     The antiseptic used in the present invention may comprise an aryl-substituted halide or aryl-substituted alcohol such as benzalkonium chloride, benzenethonium chloride, camphorated metacresol, camphorated phenol, hexylresorcinol, methylbenzethonium chloride, or phenol. The antiseptic preferably comprises about 0.05% to 0.5% by weight of the total composition, except for camphorated phenol and camphorated metacresol. For camphorated phenol, the preferred weight percentages are about 8% to 12% camphor and about 3% to 7% phenol. For camphorated metacresol, the preferred weight percentages are about 3% to 12% camphor and about 1% to 4% metacresol. 
     The preservative may comprise sodium benzoate, glydant, (also referred to as DMDM hydantoin) potassium sorbate, or chlorhexidine digluconate, or a combination thereof. The preservatives preferably comprise about 0.05% to 0.5% by weight of the total composition. 
     The surfactant, antiseptic, and preservative used in the present invention may be combined with a carrier system such as water, saline, buffer solution, or other aqueous solution suitable for topical application to wounds. The aqueous solution comprises the remainder of the total composition. 
    
    
     To further illustrate the present invention, but not by way of limitation, the following examples are provided. 
     EXAMPLE 1 
     In the development of a preferred embodiment, various combinations of preservatives and antiseptics were tested in order to develop a low toxicity wash. Those experiments were performed as follows. 
     A monolayer of L-929 mouse fibroblast cells was grown to confluency and overlaid with Minimum Essential Medium supplemented with serum, antibiotics, neutral red, and 2% agarose. The test article, a 0.5 cm×0.5 cm piece of 725871H as a positive control, a filter paper disc saturated with 0.1 ml of 0.9% SC as a filter disc control, and a 1.0 cm length piece of UP-1 as a negative control were placed on the solidified overlay surface. Following incubation for 24 hours, the culture was macroscopically examined for evidence of cell decolorization to determine the zone of cell lysis. Any decolorized zone present was examined microscopically to confirm cell lysis. 
     The greater the zone of lysis, the greater the cytotoxicity of the wound wash formulation. For six unique formulations using 4% Poloxamer 188 as a cleanser, the following zones of lysis were determined. Cytotoxicity was tested using the agarose overlay cytotoxicity test. 
     
         ______________________________________0.1% Hexylresorcinol             0.1% Benzalkonium Chloride______________________________________0.2%    0.2%     0.2%     0.2%   0.2%   0.2%chlor-  sodium   potassium                     chlor- sodium potassiumhexidine   benzoate sorbate  hexidine                            benzoate                                   sorbatediglu-                    diglu-conate                    conate7 mm    13 mm    14 mm    entire entire 12 mm                     flask  flask______________________________________ 
    
     From this testing, chlorhexidine gluconate is the preservative that gives unexpected low toxicity, while hexylresorcinol is the antiseptic agent that provides unexpectedly low cytotoxicity. Other embodiments of the invention are listed in the formulations below. 
     EXAMPLE 2 
     Eight different 4 weight percent Pluronic® surfactants (BASF Corporation, Parsippany, N.J.) were tested in combination with 0.1% hexylresorcinol and 0.2% chlorhexidine gluconate. These formulations were tested with regard to physical appearance and if of the desired appearance (clear single phase solution over the ambient temperature range) then subsequently tested for cytotoxicity. Cytotoxicity was tested using the agarose overlay test described in Example 1. 
     
         ______________________________________Generic Name    BASF Tradename                Appearance   Zone of Lysis______________________________________Meroxapol 105    Pluronic 10R-5                Phase Separation                             --Meroxapol 174    Pluronic 17R-4                Phase Separation                             --Poloxamer 124    Pluronic L44                Phase Separation                             --Poloxamer 184    Pluronic L64                Phase Separation                             --Poloxamer 188    Pluronic L68                Clear Single Phase                             7 mmPoloxamer 237    Pluronic F87                Clear Single Phase                             10 mmPoloxamer 338    Pluronic F108                Clear Single Phase                             6 mmPoloxamer 407    Pluronic F127                Clear Single Phase                             7 mm______________________________________ 
    
     From this testing, Poloxamer 188, 338, and 407 give unexpectedly low toxicity while maintaining an acceptable appearance. 
     EXAMPLE 3 
     1-20% Poloxamer (polyoxyethylene, polyoxypropylene block polymer) nonionic surfactant with 0.1% Hexylresorcinol as an antiseptic and 0.2% chlorhexidine digluconate as the preservative. 
     EXAMPLE 4 
     1-20% Poloxamine (polyoxyethylene, polyoxypropylene block polymer of ethylene diamine) nonionic surfactant with 0.1% Hexylresorcinol as an antiseptic and 0.2% chlorhexidine digluconate as the preservative. 
     EXAMPLE 5 
     1-20% Poloxamer (polyoxyethylene, polyoxypropylene block polymer) nonionic surfactant with 0.1% Hexylresorcinol as an antiseptic and 0.2% potassium sorbate as the preservative. 
     EXAMPLE 6 
     1-20% Poloxamine (polyoxyethylene, polyoxypropylene block polymer of ethylene diamine) nonionic surfactant with 0.1% Hexylresorcinol as an antiseptic and 0.2% potassium sorbate as the preservative. 
     EXAMPLE 7 
     1-20% Poloxamer (polyoxyethylene, polyoxypropylene block polymer) nonionic surfactant with 0.1% Hexylresorcinol as an antiseptic and 0.2% sodium benzoate as the preservative. 
     EXAMPLE 8 
     1-20% Poloxamine (polyoxyethylene, polyoxypropylene block polymer of ethylene diamine) nonionic surfactant with 0.1% Hexylresorcinol as an antiseptic and 0.2% sodium benzoate as the preservative. 
     Those skilled in the art will recognize that, while specific embodiments have been illustrated and described, various modifications and changes may be made without departing from the spirit and scope of the invention.