Methods and compositions using Substance P to promote wound healing

Abstract

Healing of wounds in mammalian tissue may be enhanced by the application of certain neuropeptides, optionally in combination with known growth promoting hormones. Exemplary neuropeptides include tachykinins, such as Substance P, Substance K, and the like, as well as calcitonin gene-related peptides. The compositions may further include a polymeric delivery carrier and are utilized by applying to the site of the wound. Wounds may be vascular or avascular wounds. The compositions promote elaboration of cellular matrices and development of cellular attachment mechanisms in addition to stimulating cellular proliferation.

1 . A method for promoting healing of a wound in a patient, said method comprising: 
 applying a composition to the wound in an amount sufficient to promote healing of the wound, wherein the composition comprises substance P or at least one analog thereof and a polymeric delivery vehicle; and    wherein the polymeric delivery vehicle present in the composition increases the dwell time of the substance P or at least one analog thereof such that the number of administrations of the composition required for promoting healing of the wound in the patient is reduced when compared to the number of administrations required for substance P or at least one analog thereof alone.    
     
     
         2 . The method of  claim 1 , wherein the polymeric delivery vehicle is selected from the group consisting of hyaluronic acid, chondroitin, hydroxymethyl cellulose, paraffin, cetyl alcohol, polyethylene glycol, gelatin, sodium alginate, methyl cellulose, carboxymethyl cellulose, plastibase hydrophilic gelatin, dextrin, stearyl alcohol, polyethylene glycol, polyvinyl alcohol, methoxyethylenemaleic anhydride, nanoparticles, liposomes, combinations thereof, modifications thereof and derivatives thereof.  
     
     
         3 . The method of  claim 2 , wherein the polymeric delivery vehicle is hyaluronic acid.  
     
     
         4 . The method of  claim 1 , wherein the composition further comprises at least one growth factor.  
     
     
         5 . The method of  claim 4 , wherein the at least one growth factor is selected from the group consisting of cytokines, lymphokines, interleukins, chemokines, epidermal growth factor, platelet-derived growth factor, insulin, insulin-like growth factor, transforming growth factor-β, nerve cell growth factor, fibroblast growth factor, platelet-derived growth factor, granulocyte-colony stimulating factor, granulocyte-macrophage colony stimulating factor, neurotropins, erythropoietin, thrombopoietin, myostatin, growth differentiating factor-9, hepatocyte growth factor, and combinations thereof.  
     
     
         6 . The method of  claim 5 , wherein the at least one growth factor is IGF-1.  
     
     
         7 . The method of  claim 1 , wherein the wound is further defined as a vascular wound.  
     
     
         8 . The method of  claim 7 , wherein the wound is selected from the group consisting of burns, decubitus ulcers, venous stasis ulcers, and diabetic ulcers.  
     
     
         9 . The method of  claim 1 , wherein the substance P or at least one analog thereof is present at a concentration in a range of from about 0.1 nM to about 10 mM.  
     
     
         10 . A composition, comprising: 
 Substance P or at least one analog thereof;    a polymeric delivery vehicle; and    wherein the substance P or at least one analog thereof and the polymeric delivery vehicle is present in a lotion, cream or ointment suitable for cutaneous application.    
     
     
         11 . The composition of  claim 10 , wherein the polymeric delivery vehicle is selected from the group consisting of hyaluronic acid, chondroitin, hydroxymethyl cellulose, paraffin, cetyl alcohol, polyethylene glycol, gelatin, sodium alginate, methyl cellulose, carboxymethyl cellulose, plastibase hydrophilic gelatin, dextrin, stearyl alcohol, polyethylene glycol, polyvinyl alcohol, methoxyethylenemaleic anhydride, nanoparticles, liposomes, combinations thereof, modifications thereof and derivatives thereof.  
     
     
         12 . The composition of  claim 11 , wherein the polymeric delivery vehicle is hyaluronic acid.  
     
     
         13 . The composition of  claim 10 , further comprising at least one growth factor.  
     
     
         14 . The composition of  claim 13 , wherein the at least one growth factor is selected from the group consisting of cytokines, lymphokines, interleukins, chemokines, epidermal growth factor, platelet-derived growth factor, insulin, insulin-like growth factor, transforming growth factor-β, nerve cell growth factor, fibroblast growth factor, platelet-derived growth factor, granulocyte-colony stimulating factor, granulocyte-macrophage colony stimulating factor, neurotropins, erythropoietin, thrombopoietin, myostatin, growth differentiating factor-9, hepatocyte growth factor, and combinations thereof.  
     
     
         15 . The composition of  claim 14 , wherein the at least one growth factor is IGF-1.  
     
     
         16 . A wound dressing, comprising: 
 a natural or synthetic bandage having a composition embedded or impregnated therein or coated thereon, wherein the composition comprises: 
 Substance P or at least one analog thereof; and  
 a polymeric delivery vehicle.  
   
     
     
         17 . The wound dressing of  claim 16 , wherein the polymeric delivery vehicle of the composition is selected from the group consisting of hyaluronic acid, chondroitin, hydroxymethyl cellulose, paraffin, cetyl alcohol, polyethylene glycol, gelatin, sodium alginate, methyl cellulose, carboxymethyl cellulose, plastibase hydrophilic gelatin, dextrin, stearyl alcohol, polyethylene glycol, polyvinyl alcohol, methoxyethylene-maleic anhydride, nanoparticles, liposomes, combinations thereof, modifications thereof and derivatives thereof.  
     
     
         18 . The wound dressing of  claim 17 , wherein the polymeric delivery vehicle is hyaluronic acid.  
     
     
         19 . The wound dressing of  claim 16 , wherein the composition further comprises at least one growth factor.  
     
     
         20 . The wound dressing of  claim 19 , wherein the at least one growth factor is selected from the group consisting of cytokines, lymphokines, interleukins, chemokines, epidermal growth factor, platelet-derived growth factor, insulin, insulin-like growth factor, transforming growth factor-β, nerve cell growth factor, fibroblast growth factor, platelet-derived growth factor, granulocyte-colony stimulating factor, granulocyte-macrophage colony stimulating factor, neurotropins, erythropoietin, thrombopoietin, myostatin, growth differentiating factor-9, hepatocyte growth factor, and combinations thereof.  
     
     
         21 . The wound dressing of  claim 20 , wherein the at least one growth factor is IGF-1.  
     
     
         22 . A method for promoting healing of a vascular wound in a patient, said method comprising applying a composition to the vascular wound in an amount sufficient to promote healing of the vascular wound, wherein the composition comprises substance P or at least one analog thereof.  
     
     
         23 . The method of  claim 22 , wherein the composition further comprises at least one growth factor.  
     
     
         24 . The method of  claim 23 , wherein the at least one growth factor is selected from the group consisting of cytokines, lymphokines, interleukins, chemokines, epidermal growth factor, platelet-derived growth factor, insulin, insulin-like growth factor, transforming growth factor-β, nerve cell growth factor, fibroblast growth factor, platelet-derived growth factor, granulocyte-colony stimulating factor, granulocyte-macrophage colony stimulating factor, neurotropins, erythropoietin, thrombopoietin, myostatin, growth differentiating factor-9, hepatocyte growth factor, and combinations thereof.  
     
     
         25 . The method of  claim 24 , wherein the at least one growth factor is IGF-1.  
     
     
         26 . The method of  claim 22 , wherein the wound is selected from the group consisting of burns, decubitus ulcers, venous stasis ulcers, and diabetic ulcers.  
     
     
         27 . The method of  claim 22 , wherein the substance P or at least one analog thereof is present at a concentration in a range of from about 0.1 nM to about 10 mM.