Use of CPT-1 Modulators and Compositions Thereof
The present invention describes methods for improving the appearance of skin, particularly, treating, ameliorating, preventing, delaying, and/or improving one or more signs of excess accumulation and/or production of subcutaneous fat, such as cellulite, and conditions related thereto, by topically applying compositions comprising Carnitine Palmitoyl Transferase-1 (CPT-1) modulators, optionally with other anti-lipid agents; and also describes compositions and methods for treating, preventing and improving the appearance of skin, particularly, treating, preventing, ameliorating, reducing and/or eliminating loss of subcutaneous fat in the skin, wherein the compositions include natural plant constituents that stimulate lipid synthesis.
1 . A method for treating a skin condition characterized by excess lipids, comprising topically applying to skin in need thereof an effective amount of at least one Carnitine Palmitoyl Transferase-1 (CPT-1) stimulator in a cosmetically acceptable vehicle for a time sufficient to improve the appearance of said skin.
2 . The method according to claim 1 , wherein said at least one CPT-1 stimulator is selected from the group consisting of bezafibrate, fenofibrate, capsaicin, curcumin, docosahexaenoic acid, (−)-epigallocatechin-3-gallate, caffeine, auraptene, R-alpha-lipoic acid, acetyl-L-carnitine, trans-10, cis-12 conjugated linoleic acid, soy isoflavones, L-carnitine, bitter melon, peroxisome proliferator-activated receptor beta/delta agonist GW501516, rexinoids, thiazolidinediones, alpha-linolenic acid, tetrahydro-4-methylene-2R-octyl-5-oxo-3S-furancarboxylic acid (C75), biguanide (buformin), genestein, inhibitors of BHLHB2 proteins, 3,5-dihydroxybenzoic acid derivatives, hydroxamic acid derivatives, and combinations thereof
3 . The method according to claim 1 , wherein the skin condition is cellulite.
4 . The method according to claim 1 , wherein the skin condition is acne.
5 . The method according to claim 1 , wherein the skin condition is oily skin.
6 . The method according to claim 1 , wherein said at least one CPT-1 stimulator in a cosmetically acceptable vehicle further comprises at least one other anti-lipid agent.
7 . The method according to claim 6 , wherein said at least one other anti-lipid agent comprises at least one agent selected from the group consisting of a phosphodiesterase inhibitor, an adenylate cyclase activator, a lipolysis stimulator, a beta-adrenergic receptor agonist, an alpha-2-adrenergic receptor antagonist, a xanthine analog, forskolin, a Coleus forskohlii extract, a hawthorne extract, a cola extract, isoproterenol, yohimbine, Ginkgo biloba extract, perilla oil, and combinations thereof
8 . The method according to claim 1 , wherein said at least one CPT-1 stimulator in a cosmetically acceptable vehicle further comprises at least one collagen and/or elastin stimulator.
9 . A method for reducing the re-occurrence of cellulite in an area previously affected by cellulite, comprising topically applying thereto an effective amount of at least one CPT-1 stimulator in a cosmetically acceptable vehicle, for a time sufficient to improve the appearance of said skin.
10 . A personal care or cosmetic composition for treating a skin condition characterized by excess lipids, comprising an effective amount of at least one CPT-1 stimulator in a cosmetically acceptable vehicle.
11 . The composition according to claim 10 , wherein said composition further comprises at least one other anti-lipid agent selected from the group consisting of a xanthine analog, forskolin, a Coleus forskohlii extract, a hawthorne extract, a cola extract, isoproterenol, yohimbine, Ginkgo biloba extract, perilla oil, a phosphodiesterase inhibitor, an adenylate cyclase activator, a lipolysis stimulator, a beta-adrenergic receptor agonist, an alpha-2-adrenergic receptor antagonist, and combinations thereof.
12 . The composition according to claim 10 , wherein said composition further comprises at least one collagen and/or elastin stimulator.
13 . A method for identifying CPT-1 modulators, comprising:
contacting cultured adipocytes with a candidate compound;
measuring CPT-1 expression mRNA from said adipocytes; and
comparing the CPT-1 mRNA expression levels from adipocytes treated with the compound of interest to CPT-1 mRNA levels from untreated control adipoctyes,
wherein a candiate compound which decreases CPT-1 mRNA expression levels is determined to be a CPT-1 inhibitor and a candiate compound which increases CPT-1 mRNA expression levels is determined to be a CPT-1 stimulator.
14 . A cosmetic composition comprising a CPT-1 modulator identified by the method of claim 13 .
15 . The method according to claim 13 , wherein said method further comprises:
(i) culturing adipocytes;
(ii) treating one portion of said adipocytes with a compound of interest, and treating another portion of said adipocytes identically but without a compound of interest as an adipocyte negative control, for a time and under conditions sufficient to provide synthesis of triglycerides in said adipocytes;
(iii) lysing said adipocytes and releasing said triglycerides;
(iv) measuring the released triglyceride levels; and
(v) comparing the released triglyceride levels from adipocytes treated with the compound of interest with the released triglyceride levels from control, wherein a suitable active ingredient is identified as a compound of interest which increases or decreases triglyceride levels from lysed adipocytes compared to the control.
16 . A cosmetic composition, comprising an active ingredient for the treatment of cellulite identified according to the method of claim 17 .
17 . A method for treating a skin condition characterized by insufficient subcutaneous lipids, comprising topically applying to skin in need thereof an effective amount of at least one Carnitine Palmitoyl Transferase-1 (CPT-1) inhibitor in a cosmetically acceptable vehicle for a time sufficient to improve the aesthetic appearance of said skin.
18 . A method for improving the aesthetic appearance of skin comprising topically applying to skin in need thereof an effective amount of at least one substance capable of modulating Carnitine Palmitoyl Transferase-1 (CPT-1) in human preadipocyte cells in a cosmetically acceptable vehicle for a time sufficient to improve the aesthetic appearance of said skin.
19 . A method for imparting an anti-aging benefit to skin comprising topically applying to skin in need thereof an effective amount of at least one substance capable of modulating Carnitine Palmitoyl Transferase-1 (CPT-1) in human preadipocyte cells in a cosmetically acceptable vehicle for a time sufficient to prevent, ameliorate, inhibit and/or reduce signs of dermatological aging of said skin.
20 . The method of claim 18 , where the improvement in aesthetic appearance is characterized by increased production of procollagen.