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

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.