Visfatin therapeutic agents for the treatment of acne and other conditions

Abstract

The present disclosure relates to compositions and methods for treating acne and other conditions. In particular, the compositions and methods are useful for the treatment of sebum associated conditions.

1 . A pharmaceutical composition comprising a visfatin active agent and a pharmaceutically acceptable carrier. 
     
     
         2 . The pharmaceutical composition of  claim 1  further comprising a delivery peptide. 
     
     
         3 . The pharmaceutical composition of  claim 1  wherein the visfatin active agent is a visfatin agonist. 
     
     
         4 . The pharmaceutical composition of  claim 3  comprising from about 0.001 to about 10% by weight of the visfatin agonist. 
     
     
         5 . The pharmaceutical composition of  claim 4  comprising about 1% by weight of the visfatin agonist, about 95% by weight water, about 0.2% by weight montan wax, about 0.2% by weight bee wax, about 0.2% by weight sorbitol, about 0.2% by weight shea butter, about 1% by weight borage oil, about 1% by weight  calendula  oil, about 0.2% by weight  Hamamelis  extract and about 0.1% by weight castor oil. 
     
     
         6 . The pharmaceutical composition of  claim 5  wherein the visfatin agonist comprises at least one amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6 and SEQ ID NO: 8. 
     
     
         7 . The pharmaceutical composition of  claim 6  wherein the visfatin agonist comprises the amino acid sequence of SEQ ID NO: 2. 
     
     
         8 . The pharmaceutical composition of  claim 7  which is a cream. 
     
     
         9 . The pharmaceutical composition of  claim 2  wherein the visfatin active agent is a visfatin antagonist and the delivery peptide is an amino terminally myristoylated peptide having the amino acid sequence shown in SEQ ID NO: 27. 
     
     
         10 . The pharmaceutical composition of  claim 9  wherein the visfatin antagonist is at least one siRNA targeting a nucleic acid encoding a protein comprising a sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6 and SEQ ID NO: 8. 
     
     
         11 . The pharmaceutical composition of  claim 10  comprising at least one siRNA selected from the group consisting of a first siRNA, a second siRNA, a third siRNA and a fourth siRNA; wherein the first siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 19 and SEQ ID NO: 20, the second siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 21 and SEQ ID NO: 22, the third siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 23 and SEQ ID NO: 24, and the fourth siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 25 and SEQ ID NO: 26. 
     
     
         12 . The pharmaceutical composition of  claim 10  comprising at least one siRNA selected from the group consisting of a first siRNA, a second siRNA, a third siRNA and a fourth siRNA; wherein the first siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 19 and SEQ ID NO: 20, the second siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 21 and SEQ ID NO: 22, the third siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 23 and SEQ ID NO: 24, and the fourth siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 25 and SEQ ID NO: 26. 
     
     
         13 . The pharmaceutical composition of  claim 9  comprising at least one siRNA selected from the group consisting of a first siRNA, a second siRNA and a third siRNA; wherein the first siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 9 and SEQ ID NO: 10, the second siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 13 and SEQ ID NO: 14, and the third siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 17 and SEQ ID NO: 18. 
     
     
         13 . The pharmaceutical composition of one of  claims 9 - 12  further comprising an aqueous carrier and DMSO. 
     
     
         14 . A method of treating a sebum over-production condition in a subject comprising administering a therapeutically effective amount of a visfatin antagonist, or a pharmaceutical composition containing a visfatin antagonist, to a subject with a sebum over-production condition; whereby the sebum over-production condition is treated. 
     
     
         15 . The method of  claim 14  wherein the sebum over-production condition is selected from the group consisting of acne, seborrhea, seborrhoeic dermatitis, a sebaceous cyst and sebaceous hyperplasia. 
     
     
         16 . The method of  claim 15  wherein the visfatin antagonist comprises at least one siRNA targeting a nucleic acid encoding a protein comprising a sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6 and SEQ ID NO: 8. 
     
     
         17 . The method of  claim 16  wherein the siRNA is at least one selected from the group consisting of a first siRNA, a second siRNA, a third siRNA and a fourth siRNA; wherein the first siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 19 and SEQ ID NO: 20, the second siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 21 and SEQ ID NO: 22, the third siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 23 and SEQ ID NO: 24, and the fourth siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 25 and SEQ ID NO: 26. 
     
     
         18 . The method of  claim 16  wherein the siRNA is at least one selected from the group consisting of a first siRNA, a second siRNA and a third siRNA; wherein the first siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 9 and SEQ ID NO: 10, the second siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 13 and SEQ ID NO: 14, and the third siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 17 and SEQ ID NO: 18. 
     
     
         19 . The method of  claim 15  wherein the visfatin antagonist comprises at least one compound selected from the group consisting of FK-866 and APO866. 
     
     
         20 . A method of treating acne vulgaris in a subject comprising administering a therapeutically effective amount of a visfatin antagonist, or a pharmaceutical composition containing a visfatin antagonist, to a subject with acne vulgaris; whereby the acne vulgaris is treated. 
     
     
         21 . The method of  claim 20  wherein the visfatin antagonist comprises at least one siRNA targeting a nucleic acid encoding a protein comprising a sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6 and SEQ ID NO: 8. 
     
     
         22 . The method of  claim 21  wherein the siRNA is at least one selected from the group consisting of a first siRNA, a second siRNA, a third siRNA and a fourth siRNA; wherein the first siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 19 and SEQ ID NO: 20, the second siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 21 and SEQ ID NO: 22, the third siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 23 and SEQ ID NO: 24, and the fourth siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 25 and SEQ ID NO: 26. 
     
     
         23 . The method of  claim 21  wherein the siRNA is at least one selected from the group consisting of a first siRNA, a second siRNA and a third siRNA; wherein the first siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 9 and SEQ ID NO: 10, the second siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 13 and SEQ ID NO: 14, and the third siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 17 and SEQ ID NO: 18. 
     
     
         24 . The method of  claim 20  wherein the pharmaceutical composition containing a visfatin antagonist is the pharmaceutical composition of one of  claims 9 - 12 . 
     
     
         25 . A method of treating a sebum production deficiency condition in a subject comprising administering a therapeutically effective amount of a visfatin agonist, or a pharmaceutical composition containing a visfatin agonist, to a subject with a sebum production deficiency condition; whereby the sebum production deficiency condition is treated. 
     
     
         26 . The method of  claim 25  wherein the sebum production deficiency condition is a xerosis condition associated with at least one selected from the group consisting of chapping, dermatitis, psoriasis, diabetes, renal failure, renal transplantation, hemodialysis, vitamin A deficiency and angular cheilitis. 
     
     
         27 . The method of  claim 25  wherein the visfatin agonist comprises at least one amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6 and SEQ ID NO: 8. 
     
     
         28 . The method of  claim 27  wherein the visfatin agonist composition comprises the amino acid sequence shown in SEQ ID NO: 2. 
     
     
         29 . The method of  claim 25  wherein the pharmaceutical composition containing a visfatin agonist is the pharmaceutical composition of one of  claims 3 - 8 . 
     
     
         30 . A method of increasing the sebum production of a subject comprising administering a therapeutically effective amount of a visfatin agonist, or a pharmaceutical composition containing a visfatin agonist, to the skin of a subject; whereby the sebum production of the subject is increased. 
     
     
         31 . The method of  claim 30  wherein the visfatin agonist is administered topically or intradermally. 
     
     
         32 . The method of  claim 31  wherein the visfatin agonist comprises at least one amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6 and SEQ ID NO: 8. 
     
     
         33 . The method of  claim 32  wherein the visfatin agonist comprises the amino acid sequences of SEQ ID NO: 2. 
     
     
         34 . The method of  claim 30  wherein the pharmaceutical composition containing a visfatin agonist is the pharmaceutical composition of  claims 3 - 8 . 
     
     
         35 . A method of decreasing the sebum production of a subject comprising administering a therapeutically effective amount of a visfatin antagonist, or a pharmaceutical composition containing a visfatin antagonist, to the skin of the subject, whereby the sebum production of the subject is decreased. 
     
     
         36 . The method of  claim 35  wherein the visfatin antagonist is administered topically or intradermally. 
     
     
         37 . The method of  claim 36  wherein the visfatin antagonist comprises at least one siRNA targeting a nucleic acid encoding a protein comprising a sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6 and SEQ ID NO: 8. 
     
     
         38 . The method of  claim 37  wherein the siRNA is at least one selected from the group consisting of a first siRNA, a second siRNA, a third siRNA and a fourth siRNA; wherein the first siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 19 and SEQ ID NO: 20, the second siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 21 and SEQ ID NO: 22, the third siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 23 and SEQ ID NO: 24, and the fourth siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 25 and SEQ ID NO: 26. 
     
     
         39 . The method of  claim 37  wherein the siRNA is at least one selected from the group consisting of a first siRNA, a second siRNA and a third siRNA; wherein the first siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 9 and SEQ ID NO: 10, the second siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 13 and SEQ ID NO: 14, and the third siRNA is a double stranded nucleic acid comprising the sequences shown in SEQ ID NO: 17 and SEQ ID NO: 18. 
     
     
         40 . The method of  claim 36  wherein the visfatin antagonist comprises at least one compound selected from the group consisting of FK-866 and APO866. 
     
     
         41 . The method of  claim 35  wherein the pharmaceutical composition containing a visfatin antagonist is the pharmaceutical composition of  claims 9 - 12 . 
     
     
         42 . A pharmaceutical composition adapted for treating a sebum over-production condition in a subject comprising administering a therapeutically effective amount of a visfatin antagonist to a subject with a sebum over-production condition; whereby the sebum over-production condition is treated. 
     
     
         43 . A pharmaceutical composition adapted for treating acne vulgaris in a subject comprising administering a therapeutically effective amount of a visfatin antagonist to a subject with acne vulgaris; whereby the acne vulgaris is treated. 
     
     
         44 . A pharmaceutical composition adapted for treating a sebum production deficiency condition in a subject comprising administering a therapeutically effective amount of a visfatin agonist to a subject with a sebum production deficiency condition; whereby the sebum production deficiency condition is treated. 
     
     
         45 . A pharmaceutical composition adapted for increasing the sebum production of a subject comprising administering a therapeutically effective amount of a visfatin agonist to the skin of a subject; whereby the sebum production of the subject is increased. 
     
     
         46 . A pharmaceutical composition adapted for decreasing the sebum production of a subject comprising administering a therapeutically effective amount of a visfatin antagonist to the skin of the subject, whereby the sebum production of the subject is decreased.