Method and topical formulation for treating skin conditions associated with aging

Abstract

A composition and method are provided for alleviating the dermatological signs of intrinsic and extrinsic aging. A topical formulation containing a cosmeceutically active base, wherein the formulation has a pH in the range of about 7.5 to 13.0, is applied to the skin in order to prevent or treat aging-related skin conditions such as wrinkles, dry skin, age spots, sun damage (particularly UV radiation-induced oxidative stress), blemishes, hyperpigmented skin, age spots, increased skin thickness, loss of skin elasticity and collagen content, dry skin, lentigines and melasmas. The cosmeceutically active base is either a hydroxide-releasing agent, such as an inorganic hydroxide, an inorganic oxide, or a metal salt of a weak acid, or is an organic base, particularly a nitrogenous base.

We claim:  
     
         1 . A method of treating an aging-related skin condition comprising topically applying to the skin a formulation consisting essentially of a cosmeceutically acceptable base at a concentration sufficient to provide a formulation pH in the range of approximately 7.5 to 13.0, at least one cosmeceutically acceptable excipient, and at least one cosmeceutically acceptable carrier.  
     
     
         2 . The method of  claim 1 , wherein the pH is in the range of approximately 8.0 to 11.5.  
     
     
         3 . The method of  claim 2 , wherein the pH is in the range of approximately 8.5 to 11.  
     
     
         4 . The method of  claim 1 , wherein the formulation is aqueous.  
     
     
         5 . The method of  claim 4 , wherein the aqueous formulation is selected from the group consisting of a cream, a gel, a lotion, and a paste.  
     
     
         6 . The method of  claim 5 , wherein the aqueous formulation is a cream.  
     
     
         7 . The method of  claim 5 , wherein the aqueous formulation is a gel.  
     
     
         8 . The method of  claim 5 , wherein the aqueous formulation is a lotion.  
     
     
         9 . The method of  claim 5 , wherein the aqueous formulation is a paste.  
     
     
         10 . The method of  claim 1 , wherein the cosmeceutically acceptable base is a hydroxide-releasing agent.  
     
     
         11 . The method of  claim 10 , wherein the hydroxide-releasing agent is selected from the group consisting of inorganic hydroxides, inorganic oxides, metal salts of weak acids, and mixtures thereof.  
     
     
         12 . The method of  claim 11 , wherein the hydroxide-releasing agent is an inorganic hydroxide.  
     
     
         13 . The method of  claim 12 , wherein the inorganic hydroxide is selected from the group consisting of ammonium hydroxide, alkali metal hydroxides, alkaline earth metal hydroxides, and mixtures thereof.  
     
     
         14 . The method of  claim 13 , wherein the inorganic hydroxide is selected from the group consisting of ammonium hydroxide, sodium hydroxide, calcium hydroxide, potassium hydroxide, magnesium hydroxide, and mixtures thereof.  
     
     
         15 . The method of  claim 14 , wherein the inorganic hydroxide is sodium hydroxide.  
     
     
         16 . The method of  claim 11 , wherein the hydroxide-releasing agent is an inorganic oxide.  
     
     
         17 . The method of  claim 11 , wherein the hydroxide-releasing agent is a metal salt of a weak acid.  
     
     
         18 . The method of  claim 1 , wherein the cosmeceutically acceptable base is a nitrogenous base.  
     
     
         19 . The method of  claim 1 , wherein the cosmeceutically acceptable base is an organic base.  
     
     
         20 . The method of  claim 19 , wherein the organic base is selected from primary amines, secondary amines, tertiary amines, amides, oximes, nitrogen-containing heterocycles, and urea.  
     
     
         21 . The method of  claim 20 , wherein the organic base is a primary amine, a secondary amine, or a tertiary amine.  
     
     
         22 . The method of  claim 21 , wherein the organic base has the structure NR 1 R 2 R 3  wherein R 1 , R 2  and R 3  are selected from H, alkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, hydroxyalkenyl, alkoxyalkenyl, cycloalkyl, cycloalkyl-substituted alkyl, monocyclic aryl, and monocyclic aryl-substituted alkyl, with the proviso that at least one of R 1 , R 2  and R 3  is other than H.  
     
     
         23 . The method of  claim 21 , wherein the organic base is selected from the group consisting of diethanolamine, triethanolamine, isopropanolamine, triisopropanolamine, dibutanol amine, tributanol amine, N-dodecylethanolamine, N-(2-methoxyethyl) dodecylamine, N-(2,2-dimethoxyethyl)dodecylamine, N-ethyl-N(dodecyl)ethanolamine, N-ethyl-N-(2-methoxyethyl)dodecylamine, N-ethyl-N-(2,2-dimethoxyethyl) dodecylamine, dimethyldodecylamine-N-oxide, monolauroyl lysine, dipalmitoyl lysine, dodecylamine, stearylamine, phenylethylamine, triethylamine, PEG-2 oleamine, PEG-S oleamine, dodecyl 2-(N,N-dimethylamino)propionate, bis(2-hydroxyethyl)oleylamine, and combinations thereof.  
     
     
         24 . The method of  claim 20 , wherein the organic base is an amide.  
     
     
         25 . The method of  claim 24 , wherein the amide has the structure R 4 —(CO)—NR 5 R 6  where R 4 , R 5  and R 6  are independently selected from H, alkyl, cycloalkyl, cycloalkyl-substituted alkyl, monocyclic aryl, and monocyclic aryl-substituted alkyl.  
     
     
         26 . The method of  claim 25 , wherein the amide is selected from the group consisting of hexamethyleneacetamide, hexamethyleneoctamide, hexamethylene lauramide, hexamethylene palmitamide, N,N-dimethyl formamide, N,N-dimethyl acetamide, N,N-dimethyloctamide, N,N-dimethyldecamide, toluamide, dimethyl-m-toluamide, diethyl-m-toluamide, and combinations thereof.  
     
     
         27 . The method of  claim 20 , wherein the organic base is a nitrogen-containing heterocycle.  
     
     
         28 . The method of  claim 27 , wherein the nitrogen-containing heterocycle is selected from the group consisting of 2-pyrrolidone, 1-methyl-2-pyrrolidone, 5-methyl-2-pyrrolidone, 1,5-dimethyl-2-pyrrolidone, 1-ethyl-2-pyrrolidone, 1-propyl-3-dodecylpyrrolidine, 1-dodecyclazacycloheptan-2-one, ethylene thiourea, hydantoin, oxalylurea, imidazolidilyl urea, N-octadecyl morpholine, dodecylpyridinium, N-dodecylpyrrolidine, N-dodecylpiperidine, N-dodecylhomopiperidine, and combinations thereof.  
     
     
         29 . The method of  claim 1 , wherein the formulation is applied periodically over an extended time period.  
     
     
         30 . The method of  claim 1 , wherein the formulation is applied approximately twice weekly.  
     
     
         31 . The method of  claim 1 , wherein the formulation is applied once daily.  
     
     
         32 . The method of  claim 1 , wherein the formulation is applied twice daily.  
     
     
         33 . The method of  claim 1 , wherein the formulation is applied on an as-needed basis.  
     
     
         34 . The method of  claim 29 , wherein said extended time period is at least three months.  
     
     
         35 . The method of  claim 34 , wherein said extended time period is at least four months.  
     
     
         36 . The method of  claim 1 , wherein the formulation is applied to reduce the presence of age spots.  
     
     
         37 . The method of  claim 36 , wherein the age spots are pigmented.  
     
     
         38 . The method of  claim 1 , wherein the formulation is applied to effect a substantial increase in skin thickness.  
     
     
         39 . The method of  claim 1 , wherein the formulation is applied to effect a detectable decrease in wrinkles.  
     
     
         40 . The method of  claim 1 , wherein the formulation is applied to effect a detectable decrease in skin lines.  
     
     
         41 . The method of  claim 1 , wherein the formulation is applied to photoaged skin.  
     
     
         42 . The method of  claim 1 , wherein the formulation is applied to photodamaged skin.  
     
     
         43 . The method of  claim 1 , wherein the formulation is applied to intrinsically aged skin.  
     
     
         44 . The method of  claim 1 , wherein the formulation is applied to stimulate synthesis of a dermal component selected from the group consisting of glycosaminoglycans, proteoglycans, collagen and elastic fibers.  
     
     
         45 . A method of reducing the appearance of an irregularity present within a region of an individual's skin surface, comprising topically applying to the skin surface, at least within said region, a formulation consisting essentially of a cosmeceutically acceptable base at a concentration sufficient to provide a formulation pH in the range of approximately 8.0 to 13.0, at least one cosmeceutically acceptable excipient, and at least one cosmeceutically acceptable carrier.  
     
     
         46 . A topical formulation for treating an aging-related skin condition and/or reducing the appearance of a skin irregularity, consisting essentially of a cosmeceutically acceptable base at a concentration sufficient to provide a formulation pH in the range of approximately 8.0 to 13.0, at least one cosmeceutically acceptable excipient, and at least one cosmeceutically acceptable carrier.  
     
     
         47 . The formulation of  claim 46 , wherein the pH is in the range of approximately 8.0 to 11.5.  
     
     
         48 . The formulation of  claim 47 , wherein the pH is in the range of approximately 8.5 to 11.  
     
     
         49 . The formulation of  claim 46 , wherein the at least one carrier is aqueous.  
     
     
         50 . The formulation of  claim 49 , selected from the group consisting of a cream, a gel, a lotion, and a paste.  
     
     
         51 . The formulation of  claim 50 , in the form of a cream.  
     
     
         52 . The formulation of  claim 50 , in the form of a gel.  
     
     
         53 . The formulation of  claim 50 , in the form of a lotion.  
     
     
         54 . The formulation of  claim 50 , in the form of a paste.  
     
     
         55 . The formulation of  claim 46 , wherein the cosmeceutically acceptable base is a hydroxide-releasing agent.  
     
     
         56 . The formulation of  claim 55 , wherein the hydroxide-releasing agent is selected from the group consisting of inorganic hydroxides, inorganic oxides, metal salts of weak acids, and mixtures thereof.  
     
     
         57 . The formulation of  claim 56 , wherein the hydroxide-releasing agent is an inorganic hydroxide.  
     
     
         58 . The formulation of  claim 57 , wherein the inorganic hydroxide is selected from the group consisting of ammonium hydroxide, alkali metal hydroxides, alkaline earth metal hydroxides, and mixtures thereof.  
     
     
         59 . The formulation of  claim 58 , wherein the inorganic hydroxide is selected from the group consisting of ammonium hydroxide, sodium hydroxide, calcium hydroxide, potassium hydroxide, magnesium hydroxide, and mixtures thereof.  
     
     
         60 . The formulation of  claim 59 , wherein the inorganic hydroxide is sodium hydroxide.  
     
     
         61 . The formulation of  claim 56 , wherein the hydroxide-releasing agent is an inorganic oxide.  
     
     
         62 . The formulation of  claim 56 , wherein the hydroxide-releasing agent is a metal salt of a weak acid.  
     
     
         63 . The formulation of  claim 46 , wherein the cosmeceutically acceptable base is a nitrogenous base.  
     
     
         64 . The formulation of  claim 46 , wherein the cosmeceutically acceptable base is an organic base.  
     
     
         65 . The formulation of  claim 64 , wherein the organic base is selected from primary amines, secondary amines, tertiary amines, amides, oximes, nitrogen-containing heterocycles, and urea.  
     
     
         66 . The formulation of  claim 65 , wherein the organic base is a primary amine, a secondary amine, or a tertiary amine.  
     
     
         67 . The formulation of  claim 66 , wherein the organic base has the structure NR 1 R 2 R 3  wherein R 1 , R 2  and R 3  are selected from H, alkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, hydroxyalkenyl, alkoxyalkenyl, cycloalkyl, cycloalkyl-substituted alkyl, monocyclic aryl, and monocyclic aryl-substituted alkyl, with the proviso that at least one of R 1 , R 2  and R 3  is other than H.  
     
     
         68 . The formulation of  claim 67 , wherein the organic base is selected from the group consisting of diethanolamine, triethanolamine, isopropanolamine, triisopropanolamine, dibutanol amine, tributanol amine, N-dodecylethanolamine, N-(2-methoxyethyl) dodecylamine, N-(2,2-dimethoxyethyl)dodecylamine, N-ethyl-N-(dodecyl)ethanolamine, N-ethyl-N-(2-methoxyethyl)dodecylamine, N-ethyl-N-(2,2-dimethoxyethyl) dodecylamine, dimethyldodecylamine-N-oxide, monolauroyl lysine, dipalmitoyl lysine, dodecylamine, stearylamine, phenylethylamine, triethylamine, PEG-2 oleamine, PEG-5 oleamine, dodecyl 2-(N,N-dimethylamino)propionate, bis(2-hydroxyethyl)oleylamine, and combinations thereof.  
     
     
         69 . The formulation of  claim 65 , wherein the organic base is an amide.  
     
     
         70 . The formulation of  claim 69 , wherein the amide has the structure R 4 —(CO)—NR 5 R 6  where R 4 , R 5  and R 6  are independently selected from H, alkyl, cycloalkyl, cycloalkyl-substituted alkyl, monocyclic aryl, and monocyclic aryl-substituted alkyl.  
     
     
         71 . The formulation of  claim 70 , wherein the amide is selected from the group consisting of hexamethyleneacetamide, hexamethyleneoctamide, hexamethylene lauramide, hexamethylene palmitamide, N,N-dimethyl formamide, N,N-dimethyl acetamide, N,N-dimethyloctamide, N,N-dimethyldecamide, toluamide, dimethyl-m-toluamide, diethyl-m-toluamide, and combinations thereof.  
     
     
         72 . The formulation of  claim 65 , wherein the organic base is a nitrogen-containing heterocycle.  
     
     
         73 . The formulation of  claim 72 , wherein the nitrogen-containing heterocycle is selected from the group consisting of 2-pyrrolidone, 1-methyl-2-pyrrolidone, 5-methyl-2-pyrrolidone, 1,5-dimethyl-2-pyrrolidone, 1-ethyl-2-pyrrolidone, 1-propyl-3-dodecylpyrrolidine, 1-dodecyclazacycloheptan-2-one, ethylene thiourea, hydantoin, oxalylurea, imidazolidilyl urea, N-octadecyl morpholine, dodecylpyridinium, N-dodecylpyrrolidine, N-dodecylpiperidine, N-dodecylhomopiperidine, and combinations thereof.  
     
     
         74 . A topical formulation for treating an aging-related skin condition and/or reducing the appearance of a skin irregularity, consisting essentially of: 
 a cosmeceutically acceptable base at a concentration sufficient to provide a formulation pH in the range of approximately 8.0 to 13.0;    at least one pharmacologically active agent suitable for topical drug delivery and effective to treat the aging-related skin condition and/or reduce the appearance of a skin irregularity;    at least one cosmeceutically acceptable excipient; and    at least one cosmeceutically acceptable carrier.    
     
     
         75 . A sunscreen formulation for treating an aging-related skin condition and/or reducing the appearance of a skin irregularity, consisting essentially of: 
 a cosmeceutically acceptable base at a concentration sufficient to provide a formulation pH in the range of approximately 8.0 to 13.0;    at least one sunscreen;    at least one cosmeceutically acceptable excipient; and    at least one cosmeceutically acceptable carrier.    
     
     
         76 . A self-tanning formulation for treating an aging-related skin condition and/or reducing the appearance of a skin irregularity, consisting essentially of: 
 a cosmeceutically acceptable base at a concentration sufficient to provide a formulation pH in the range of approximately 8.0 to 13.0;    at least one agent that promotes the appearance of tanned skin without exposure to the sun;    at least one cosmeceutically acceptable excipient; and    at least one cosmeceutically acceptable carrier.