Advanced Formulations and Therapies for Treating Hard-to-Heal Wounds

Abstract

A method for healing a hard-to-heal wound including the steps of: topically administering a wound healing composition to a wounded area, wherein the wound healing composition includes, at least one of: (a) a medicament characterized as a calcium channel blocker or pharmaceutically acceptable salts or solvates thereof; (b) a medicament characterized as an alpha-adrenergic antagonist or pharmaceutically acceptable salts or solvates thereof; (c) a medicament characterized as a direct vasodilator or pharmaceutically acceptable salts or solvates thereof; and (d) a medicament characterized as a phosphodiesterase type five inhibitor or pharmaceutically acceptable salts or solvates thereof; and (e) a hemorrheologic agent or pharmaceutically acceptable salts or solvates thereof; (f) a primary dermal penetrating agent or pharmaceutically acceptable salts or solvates thereof: and (g) a topical stimulating agent or pharmaceutically acceptable salts or solvates thereof.

What is claimed and desired to be secured by Letters Patent of the United States is: 
     
         1 . A method for healing a wound, comprising the steps of:
 topically administering a wound healing composition to a wounded area, wherein the wound healing composition comprises:
 a medicament characterized as a calcium channel blocker or pharmaceutically acceptable salts or solvates thereof; 
 a medicament characterized as a hemorrheologic agent or pharmaceutically acceptable salts or solvates thereof; 
 a dermal penetrating agent or pharmaceutically acceptable salts or solvates thereof; and 
 a topical stimulating agent or pharmaceutically acceptable salts or solvates thereof. 
   
     
     
         2 . The method for healing a wound according to  claim 1 , wherein the step of topically administering a wound healing composition comprises the step of topically administering an effective amount of a wound healing composition to the wounded area. 
     
     
         3 . The method for healing a wound according to  claim 1 , wherein the step of topically administering a wound healing composition comprises the step of topically administering a wound healing composition which comprises a medicament represented by the following chemical structure: 
       
         
           
           
               
               
           
         
         wherein R 1-11  are the same or different and comprise H, a hydroxy group, a primary, secondary, or tertiary amine, a halide, NO 2 , SO 3 H, CN, a straight or branched alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkenyl, alkynyl, or carbonyl group containing approximately 1 to approximately 50 carbon atom(s), a silyl or siloxyl group containing approximately 1 to approximately 50 silicon atom(s), and combinations thereof, wherein X 1-4  are the same or different and comprise oxygen, sulfur, or selenium; and wherein Y 1  comprises nitrogen or phosphorus. 
       
     
     
         4 . The method for healing a wound according to  claim 1 , wherein the step of topically administering a wound healing composition comprises the step of topically administering a wound healing composition which comprises a medicament represented by the following chemical structure: 
       
         
           
           
               
               
           
         
         wherein R 1-8  are the same or different and comprise H, a hydroxy group, a primary, secondary, or tertiary amine, a straight or branched alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkenyl, alkynyl, or carbonyl group containing approximately 1 to approximately 50 carbon atom(s), a silyl or siloxyl group containing approximately 1 to approximately 50 silicon atom(s), and combinations thereof. 
       
     
     
         5 . The method for healing a wound according to  claim 4 , wherein the step of topically administering a wound healing composition comprises the step of topically administering an effective amount of a wound healing composition to the wounded area. 
     
     
         6 . The method for healing a wound according to  claim 1 , wherein the step of topically administering a wound healing composition comprises the step of topically administering a wound healing composition which comprises a medicament represented by the following chemical structure: 
       
         
           
           
               
               
           
         
       
     
     
         7 . The method for healing a wound according to  claim 6 , wherein the step of topically administering a wound healing composition comprises the step of topically administering an effective amount of a wound healing composition to the wounded area. 
     
     
         8 . The method for healing a wound according to  claim 1 , wherein the step of topically administering a wound healing composition comprises the step of topically administering a wound healing composition which comprises a medicament represented by the following chemical structure: 
       
         
           
           
               
               
           
         
         wherein R 1-4  are the same or different and comprise H, a hydroxy group, a primary, secondary, or tertiary amine, a straight or branched alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkenyl, alkynyl, or carbonyl group containing approximately 1 to approximately 50 carbon atom(s), a silyl or siloxyl group containing approximately 1 to approximately 50 silicon atom(s), and combinations thereof; wherein X 1-2  are the same or different and comprise oxygen, sulfur, or selenium; and wherein Y 1-4  are the same or different and comprise nitrogen or phosphorus. 
       
     
     
         9 . The method for healing a wound according to  claim 1 , wherein the step of topically administering a wound healing composition comprises the step of topically administering a wound healing composition which comprises a medicament represented by the following chemical structure: 
       
         
           
           
               
               
           
         
         wherein R 1-5  are the same or different and comprise H, a hydroxy group, a primary, secondary, or tertiary amine, a straight or branched alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkenyl, alkynyl, or carbonyl group containing approximately 1 to approximately 50 carbon atom(s), a silyl or siloxyl group containing approximately 1 to approximately 50 silicon atom(s), and combinations thereof. 
       
     
     
         10 . The method for healing a wound according to  claim 9 , wherein the step of topically administering a wound healing composition comprises the step of topically administering an effective amount of a wound healing composition to the wounded area. 
     
     
         11 . The method for healing a wound according to  claim 1 , wherein the step of topically administering a wound healing composition comprises the step of topically administering a wound healing composition which comprises a medicament represented by the following chemical structure: 
       
         
           
           
               
               
           
         
       
     
     
         12 . The method for healing a wound according to  claim 11 , wherein the step of topically administering a wound healing composition comprises the step of topically administering an effective amount of a wound healing composition to the wounded area. 
     
     
         13 . The method for healing a wound according to  claim 1 , wherein the step of topically administering a wound healing composition comprises the step of topically administering a wound healing composition which comprises a dermal penetrating agent represented by the following chemical structure:
   R 1 —X 1 —R 2 —X 2 —R 3 —X 3 —R 4  
   wherein R 1-4  are the same or different and comprise H, a hydroxy group, a primary, secondary, or tertiary amine, a straight or branched alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkenyl, alkynyl, or carbonyl group containing approximately 1 to approximately 50 carbon atom(s), a silyl or siloxyl group containing approximately 1 to approximately 50 silicon atom(s), and combinations thereof; and wherein X 1-3  are the same or different and comprise oxygen, sulfur, or selenium.   
     
     
         14 . The method for healing a wound according to  claim 1 , wherein the step of topically administering a wound healing composition comprises the step of topically administering a wound healing composition which comprises a dermal penetrating agent represented by the following chemical structure: 
       
         
           
           
               
               
           
         
         wherein R 1-13  are the same or different and comprise H, a hydroxy group, a primary, secondary, or tertiary amine, a straight or branched alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkenyl, alkynyl, or carbonyl group containing approximately 1 to approximately 50 carbon atom(s), a silyl or siloxyl group containing approximately 1 to approximately 50 silicon atom(s), and combinations thereof. 
       
     
     
         15 . The method for healing a wound according to  claim 14 , wherein the step of topically administering a wound healing composition comprises the step of topically administering an effective amount of a wound healing composition to the wounded area. 
     
     
         16 . The method for healing a wound according to  claim 1 , wherein the step of topically administering a wound healing composition comprises the step of topically administering a wound healing composition which comprises a dermal penetrating agent represented by the following chemical structure: 
       
         
           
           
               
               
           
         
       
     
     
         17 . The method for healing a wound according to  claim 1 , wherein the step of topically administering a wound healing composition comprises the step of topically administering a wound healing composition which comprises a first medicament represented by the following chemical structure: 
       
         
           
           
               
               
           
         
         wherein R 1-11  are the same or different and comprise H, a hydroxy group, a primary, secondary, or tertiary amine, a halide, NO 2 , SO 3 H, CN, a straight or branched alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkenyl, alkynyl, or carbonyl group containing approximately 1 to approximately 50 carbon atom(s), a silyl or siloxyl group containing approximately 1 to approximately 50 silicon atom(s), and combinations thereof, wherein X 1-4  are the same or different and comprise oxygen, sulfur, or selenium; and wherein Y 1  comprises nitrogen or phosphorus; a second medicament represented by the following chemical structure: 
       
       
         
           
           
               
               
           
         
         wherein R 1-4  are the same or different and comprise H, a hydroxy group, a primary, secondary, or tertiary amine, a straight or branched alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkenyl, alkynyl, or carbonyl group containing approximately 1 to approximately 50 carbon atom(s), a silyl or siloxyl group containing approximately 1 to approximately 50 silicon atom(s), and combinations thereof; wherein X 1-2  are the same or different and comprise oxygen, sulfur, or selenium; and wherein Y 1-4  are the same or different and comprise nitrogen or phosphorus; and a dermal penetrating agent represented by the following chemical structure:
   R 1 —X 1 —R 2 —X 2 —R 3 —X 3 —R 4  
 
 
         wherein R 1-4  are the same or different and comprise H, a hydroxy group, a primary, secondary, or tertiary amine, a straight or branched alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkenyl, alkynyl, or carbonyl group containing approximately 1 to approximately 50 carbon atom(s), a silyl or siloxyl group containing approximately 1 to approximately 50 silicon atom(s), and combinations thereof; and wherein X 1-3  are the same or different and comprise oxygen, sulfur, or selenium. 
       
     
     
         18 . The method for healing a wound according to  claim 17 , wherein the step of topically administering a wound healing composition comprises the step of topically administering an effective amount of a wound healing composition to the wounded area. 
     
     
         19 . The method for healing a wound according to  claim 1 , wherein the step of topically administering a wound healing composition comprises the step of topically administering a wound healing composition which comprises a first medicament comprising 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-dimethyl ester and pharmaceutically acceptable salts or solvates thereof; a second medicament comprising 1-(5-oxohexyl)-3,7-dimethylxanthine and pharmaceutically acceptable salts or solvates thereof; and a dermal penetrating agent comprising 2-(2-ethoxy-ethoxy)-ethanol and pharmaceutically acceptable salts or solvates thereof. 
     
     
         20 . A method for healing a hard-to-heal wound of diabetic origin otherwise subject to amputation, comprising the steps of:
 topically administering a wound healing composition only to the outer periphery of the wounded area of diabetic origin, wherein the wound healing composition comprises at least one of: (a) a medicament characterized as a calcium channel blocker or pharmaceutically acceptable salts or solvates thereof; (b) a medicament characterized as an alpha-adrenergic antagonist or pharmaceutically acceptable salts or solvates thereof; (c) a medicament characterized as a direct vasodilator or pharmaceutically acceptable salts or solvates thereof; and (d) a medicament characterized as a phosphodiesterase type five inhibitor or pharmaceutically acceptable salts or solvates thereof; and (e) a hemorrheologic agent or pharmaceutically acceptable salts or solvates thereof; (f) a primary dermal penetrating agent or pharmaceutically acceptable salts or solvates thereof: and (g) a topical stimulating agent or pharmaceutically acceptable salts or solvates thereof.