Deepithelialized skin diffusion cell system

Abstract

A deepithelialized skin cell diffusion system which can be used to select topical and cream formulations containing wound healing promoters such as plasma fibronectin. The formulations provide slow release and increased contact time of fibronectin or other wound healing promoters to the wound site leading to its effective absorption.

I claim:  
     
         1 . A formulation for topical wound healing having an Abs value greater than 7.8, the Abs value being the percentage of a labeled wound healing promoter absorbed after 12 hours in a diffusion cell system, wherein the diffusion cell system comprises: 
 a donor compartment;    a receptor compartment; and    a deepithelialized skin sample having a deepithelialized side and a dermal side, wherein the skin sample is placed so that the deepithelialized side faces into the donor compartment and the dermal side faces into the receptor compartment.    
     
     
         2 . The formulation according to  claim 1 , wherein the deepithelialized skin sample is a human sample from which an eight-micrometer section of the epidermal surface has been removed.  
     
     
         3 . A formulation for topical wound healing having an Abs value greater than 7.8, the Abs value being the percentage of a labeled wound healing promoter absorbed after 12 hours in a diffusion cell system, wherein the diffusion cell system comprises: 
 a donor compartment;    a receptor compartment; and    a deepithelialized skin sample having a deepithelialized side and a dermal side, wherein the skin sample is placed so that the deepithelialized side faces into the donor compartment and the dermal side faces into the receptor compartment, and    wherein the wound healing promoter comprises at least one extracellular matrix protein selected from the group consisting of fibronectin, thrombospondin, laminin, vitronectin and fibrinogen.    
     
     
         4 . The formulation according to  claim 1 , wherein the wound healing promoter comprises at least one growth factor.  
     
     
         5 . The formulation according to  claim 1 , wherein the receptor compartment is connected to a circulating buffer circuit containing a buffer solution.  
     
     
         6 . The formulation according to  claim 5 , wherein the buffer solution is maintained at 37° C. and the deepithelialized skin side is maintained at 32° C.  
     
     
         7 . The formulation according to  claim 1 , wherein the deepithelialized skin sample is obtained from a species which serves as an animal model for human skin.  
     
     
         8 . The formulation according to  claim 7 , wherein the species is selected from the group consisting of human being, domestic pig, laboratory rabbit, laboratory guinea pig, and laboratory rodents.  
     
     
         9 . The formulation according to  claim 1 , wherein the deepithelialized skin sample is obtained from a domestic, laboratory, or companion animal.  
     
     
         10 . A method for promoting healing of a skin wound, comprising the steps of applying the formulation of  claim 1  to a wound.  
     
     
         11 . An aqueous gel formulation for topical wound healing having an Abs value of at least 13.4, the Abs value being the percentage of labeled wound healing promoter absorbed after 12 hours in a diffusion cell system, wherein the diffusion cell system comprises: 
 a donor compartment;    a receptor compartment; and    a deepithelialized skin sample having a deepithelialized side and a dermal side, wherein the skin sample is placed so that the deepithelialized side faces into the donor compartment and the dermal side faces into the receptor compartment.    
     
     
         12 . The method according to  claim 11 , wherein the deepithelialized skin sample is a human sample from which an eight-micrometer section of the epidermal surface has been removed.  
     
     
         13 . An aqueous gel formulation for topical wound healing having an Abs value of at least 13.4, the Abs value being the percentage of labeled wound healing promoter absorbed after 12 hours in a diffusion cell system, wherein the diffusion cell sytem comprises: 
 a donor compartment;    a receptor compartment; and    a deepithelialized skin sample having a deepithelialized side and a dermal side, wherein the skin sample is placed so that the deepithelialized side faces into the donor compartment and the dermal side faces into the receptor compartment,    wherein the wound healing promoter comprises at least one extracellular matrix protein selected from the group consisting of fibronectin, thrombospondin, laminin, vitronectin and fibrinogen.    
     
     
         14 . The aqueous gel formulation according to  claim 11 , wherein the wound healing promoter comprises at least one growth factor.  
     
     
         15 . The aqueous gel formulation according to  claim 11 , wherein the receptor compartment is connected to a circulating buffer circuit containing a buffer solution. wherein the buffer solution is maintained at 37° C. and the deepithelialized skin side is maintained at 32° C.  
     
     
         16 . The aqueous gel formulation according to  claim 15 , wherein the buffer solution is maintained at 37° C. and the deepithelialized skin side is maintained at 32° C.  
     
     
         17 . The aqueous gel formulation according to  claim 11 , wherein the deepithelialized skin sample is obtained from a species which serves as an animal model for human skin.  
     
     
         18 . The aqueous gel formulation according to  claim 17 , wherein the species is selected from the group consisting of human being, domestic pig, laboratory rabbit, laboratory guinea pig, and laboratory rodents.  
     
     
         19 . The formulation according to  claim 11 , wherein the deepithelialized skin sample is obtained from a domestic, laboratory, or companion animal.  
     
     
         20 . A method for promoting healing of a skin wound, comprising the steps of applying the formulation of  claim 11  to a wound.  
     
     
         21 . A method of measuring the absorption by deepithelialized skin of a premeasured amount of an active ingredient contained in a topical formulation comprising the steps of: 
 a) applying the topical formulation containing premeasured amount of an active ingredient to the deepithelialized skin sample in the diffusion cell system comprising: 
 a donor compartment;  
 a receptor compartment; and  
 a deepithelialized skin sample having a deepithelialized side and a dermal side, wherein the skin sample is placed so that the deepithelialized side faces into the donor compartment and the dermal side faces in the receptor compartment;  
   b) measuring the amount of active ingredient measured in the deepithelialized skin sample and in the receptor compartment after a period of time; and    c) dividing the amount of active ingredient measured in step b) by the amount applied in the deepithelialized skin sample of step a).    
     
     
         22 . The method of measuring the absorption according to  claim 21 , wherein the receptor compartment is connected to a circulating buffer circuit containing a buffer solution.  
     
     
         23 . The method of measuring the absorption according to  claim 22 , wherein the buffer solution is maintained at 37° C. and the deepithelialized skin side is maintained at 32° C.  
     
     
         24 . The method of measuring the absorption according to  claim 21 , wherein the deepithelialized skin sample is obtained from a species which serves as an animal model for human skin.  
     
     
         25 . The method of measuring the absorption according to  claim 24 , wherein the species is selected from the group consisting of human being, domestic pig, laboratory rabbit, laboratory guinea pig, and laboratory rodents.  
     
     
         26 . The method according to  claim 21 , wherein the deepithelialized skin sample is obtained from a domestic, laboratory, or companion animal.  
     
     
         27 . The method according to  claim 21 , wherein the active ingredient is prepared in a salt-free solution.