Patent Publication Number: US-2009234305-A1

Title: Temporary skin substitute comprised of biological compounds of plant and animal origins

Description:
RELATED APPLICATIONS 
     This application is a Continuation-in-Part of application Ser. No. 12/049,321 which is currently copending. 
    
    
     FIELD OF THE INVENTION 
     This invention relates to the fields of artificial skin substitutes and therapeutic delivery of wound healing agents. 
     BACKGROUND OF THE INVENTION 
     The present invention is a device and methods of incorporating wound healing agents, comprised of biological compounds of plant and animal origin, into the three dimensional structure of the precision, porous silicone/nylon membrane described in U.S. patent application Ser. No. 12/049,321 and U.S. patent application Ser. No. 12/326,373, to the current inventor. The present invention performs this function without cross-linking agents in a manner that does not compromise the physical properties of the skin substitute, comprised of stretchability, flexibility, conformability, and other features, nor the aesthetics of the skin substitute. 
     This new skin substitute can be sterilized using E Beam irradiation without changing its aesthetic, biological or physical properties. 
     Previously, in the above-referenced applications, methods were described for incorporation of porcine type 1 pharmaceutical grade gelatin (collagen peptides) into the three dimensional structure of the precision porous silicone/nylon membrane. Previous patents to this inventor (Biobrane patent) identified collagen peptide as the best agent for initiating acute adherence of a skin substitute to the wound surface. This is a direct result of interacting with fibrin present in the wound. 
     The present invention provides similar methods for incorporating the following biological compounds; Vitamin E, Vitamin C, Chondroitin 4 Sulfate, Chondroitin 6 Sulfate and Immuno-10 (a highly purified fraction of Aloe Vera) in addition to porcine collagen peptide into the three dimensional structure of the precision porous silicone/nylon membrane of the referenced applications. Each of these compounds impart a unique biological activity that enhances wound healing. 
     The Immuno-10 material, U.S. Pat. Nos. 6,436,679, 6,271,214 and 6,133,440, is known for its immunostimulating and immunomodulating properties. Chondroitin Sulfate (4 and 6) is known for its antiflammatory properties. Vitamin E and C are known for their antioxidant properties. Each biological compound has excellent stability at room temperature and is not damaged by exposure to E Beam irradiation. 
     The ability to directly contact the acute wound surface with these six biological components enables wound healing to occur at a faster rate than normal. The desirable attributes of the skin substitute characterized in the referenced patent applications to this inventor are further enhanced by the addition of five active biological compounds. None of these capabilities are taught in the prior art. 
     SUMMARY OF THE INVENTION 
     The present invention is a method of applying a plurality of biological substances to the surface of a wound by means of a specified, proprietary temporary skin substitute wound dressing. The apparatus is the dressing, comprised of a nylon mesh with proprietary three-dimensional shape and a porous silicone membrane bound to the mesh. 
     In addition to the substance delivery properties of the invention, the nylon weave in the invention serves to implement three important functions in wound healing, namely fluid transfer, clot support, and skin cell growth. The nylon weave possesses a three-dimensional structure, as in  FIG. 4  and  FIG. 5 , that provides physical and structural support for clots as the skin begins to heal. The porosity of the skin substitute is maintained by the weave at the pore holes, permitting transmission of fluids and preventing transmission of small foreign bodies. The three-dimensional structure of the weave also allows new skin cells to grow in a protected environment. 
     The substance delivery methods revolve around the application of a plurality of biological and other non-biological substances on and into the apparatus&#39;s nylon mesh for the purposes of treating surface injuries of the skin. 
    
    
     
       BRIEF OVERVIEW OF THE DRAWINGS AND TABLES 
         FIG. 1 . Vacuum popped hole, standard nylon 
         FIG. 2 . Vacuum-popped hole, low adhesion nylon 
         FIG. 3 . Punctured hole 
         FIG. 4 . Top view of hole showing weave 
         FIG. 5 . Cross-section of vacuum-popped hole showing mesh 
     
    
    
     Table 1. Biologicals per square cm 
     DETAILED DESCRIPTION OF THE INVENTION 
     As in  FIG. 4  and  FIG. 5 , the apparatus  100  of the invention is comprised of a silicone membrane  101  with a plurality of holes  102  created in it for porosity. As in  FIG. 4  and  FIG. 5 , physically connected to the membranes  101  by a weave attachment means is a nylon weave  103  comprised of a plurality of interwoven fibers  110  that prevents the passage of gross physical objects larger than 0.001″ through the holes  102 . 
     The range of hole diameters preferred in the present invention is 0.75 mm to 1.05 mm and at holes centered at ¼″-⅓″, providing minimal fluid accumulation beneath the apparatus  100 , which will reduce infection complications and maximize wound healing. This is shown in  FIGS. 2 and 3 . 
       FIG. 1  represents a prior art skin substitute, Biobrane™, which is produced by means of puncturing holes through a similar silicone/nylon weave apparatus. Note that the fibers in the holes are disturbed or destroyed where the fibers  110  in the holes of  FIG. 2  and  FIG. 3  are relatively undamaged. 
     The top surface  105  of the apparatus is represented by the silicone membranes  101 , the lower surface  106  represented by the nylon weave  103 . The two surfaces  105 ,  106  comprise the two locations for biological and non-biological substances to be applied to the apparatus  100 . 
     The method of use for the apparatus  100  is as a wound dressing or covering. A surface wound of an area determined by the available area of the apparatus  100  can be covered such that fluids can drain from wound through the membrane holes  102 , through the weave  13 . Similarly, fluids containing drugs or therapeutic agents can pass through the pore holes  102  for the purpose of treating the wound. 
     As shown in  FIG. 4  and  FIG. 5 , the three-dimensional nature of the weave  103  is designed to provide clot support and cell growth support by means of the structure of the weave  103  itself. The weave  103  is in two qualities, Denier 15/2 and 12/1. Each provides sufficient three-dimensional presence to perform the above functions. 
     The three-dimensional structure of the weave  103  in combination with use of collagen peptides in the apparatus also provides improved wound adherence for the apparatus; wound adherence is a key property for any skin substitute. 
     To properly implement the three-dimensional structure of the weave  103  at the pore holes  102 , the apparatus  100  is manufactured by means of using vacuum technology instead of puncturing the pore holes  102  into apparatus  100 .  FIG. 1  shows a typical result at the pore hole as a consequence of puncturing, with disturbed or destroyed weave fibers.  FIG. 2  and  FIG. 3  show the pore holes  102  produced by the vacuum technology, with an essentially undisturbed weave  103 , it&#39;s three-dimensional structure intact. 
     Another method of use of the invention is for therapeutic agents, biological or non-biological, to be applied to the lower surface  106  of the apparatus for direct contact with the wound and surrounding skin. 
     A third method, and the preferred embodiment of the invention, is the impregnation of the apparatus  100  material itself with substances taken from the list of Vitamin E, Vitamin C, Chondroitin 4 Sulfate, Chondroitin 6 Sulfate and a highly purified fraction of aloe vera (Immuno-10™), and porcine collagen peptide. These substances will be released slowly over time to the covered skin as it comes in contact with the apparatus. Table 1 shows a typical proportion by weight of therapeutic agent applied to the invention. 
     The Immuno-10™ aloe vera extract is selected for its purity, but the effect provided by aloe vera to the skin is claimed for any fraction of aloe vera used with the invention. 
     The technology to create the apparatus above and the method listed as the preferred embodiment of this invention, and other methods, are possible and are within the contemplation of this patent. 
     
       
         
           
               
             
               
                 TABLE 1 
               
               
                   
               
               
                 Biologicals per Square Centimeter 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 Biologicals 
                   
                   
               
               
                   
                 Gelatin 
                 2.50000 g 
                 20.62% 
               
               
                   
                 Aloe 
                 7.50000 g 
                 61.86% 
               
               
                   
                 Chondroitin Sul. 
                 0.12500 g 
                 1.03% 
               
               
                   
                 Vitamin E 
                 1.00000 g 
                 8.25% 
               
               
                   
                 Vitamin C 
                 1.00000 g 
                 8.25% 
               
               
                   
                 Total Biologicals 
                 12.12500 g  
               
               
                   
                 Pre-Biological wt. 
                 2.56000 g 
                 85.62% 
               
               
                   
                 Post-Biological wt. 
                 2.99000 g 
                 100.00% 
               
               
                   
                 Qnty per 15.24 × 30.48 
                 0.43000 g 
                 14.38% 
               
               
                   
                 Qnty of Material/cm = 
                 0.00093 g 
               
               
                   
                 Biologicals 
                 0.00093 g 
               
               
                   
                 Qnty per cm 2   
               
               
                   
                 Gellatin (g) 
                 0.00019 g 
               
               
                   
                 Aloe (g) 
                 0.00057 g 
               
               
                   
                 Chondroitin Sul. (g) 
                 0.00001 g 
               
               
                   
                 Vitamin E (g) 
                 0.00008 g 
               
               
                   
                 Vitamin C (g) 
                 0.00008 g 
               
               
                   
                 Total Biologicals (g) 
                 0.00093 g