Putrescine topical formulations

Abstract

The present invention describes complex topical aqueous compositions for the effective delivery of active ingredients such as putrescine and Vitamin C into the skin. These compositions may be used in a variety of cosmetic and therapeutic applications including for reducing or preventing skin's signs of aging, for promoting wound healing, for reducing or preventing the formation of hypertrophic scar tissue, for reducing or preventing skin irritation and/or inflammation.

1 . An aqueous topical composition comprising (i) a primary polyamine; (ii) at least one of Vitamin C, Vitamin E (alpha tocopherol), a jojoba ester or a peptide; and (iii) (a) at least one viscosity increasing agent/anticaking agent, (b) at least one a binder/stabilizer; (c) at least one skin conditioning agent; (d) at least one humectant, binder, emulsion stabilizer, surfactant and viscosity increasing agent; (e) at least one rheology modifier; or (f) any combination of at least two of any one of (a) to (e). 
     
     
         2 . The topical composition of  claim 1 , wherein said (i) primary polyamine is a primary aliphatic lower-alkyl (C1-5) monoamine; a primary aliphatic alkylamine; or a primary aliphatic lower-alkyl (C1-5) polyamine; (ii) comprises Vitamin C, wherein the Vitamin C consists of L-ascorbic acid, 3-O-ethyl ascorbic acid (ETVC), ascorbyl palmitate or any combination of at least two thereof, wherein the concentration of Vitamin C's is between about 0.05% w/w and about 20% w/w; and/or comprises Vitamin E, wherein the concentration of Vitamin E is between about 0.1% w/w and about 1% w/w; or about 0.3% w/w; and/or comprises at least on peptide; and/or comprises a jojoba ester, wherein the concentration of jojoba ester is between about 0.1% w/w and about 1.5% w/w; or about 1%; and/or (iii) comprises at least one viscosity increasing agent/anticaking agent, wherein the concentration of the at least one viscosity increasing agent/anticaking agent is between about 0.6% w/w and about 3% w/w; and/or comprises at least one binder/stabilizer, wherein the concentration of the at least one binder/stabilizer is between about 0.1% w/w and about 0.9% w/w; and/or comprises at least one skin conditioning agent, wherein the concentration of the at least one skin conditioning agent is between about 2% w/w and about 36% w/w; and/or comprises at least one at least one humectant, binder, emulsion stabilizer, surfactant and viscosity increasing agent, wherein the concentration of the at least one at least one humectant, binder, emulsion stabilizer, surfactant and viscosity increasing agent is between about 1% w/w and about 5% w/w; and/or comprises at least one at least one rheology modifier, wherein the concentration of the at least one rheology modifier is between about 1% w/w and 3% w/w. 
     
     
         3 . The topical composition of  claim 2 , wherein said primary aliphatic lower-alkyl (C1-5) monoamine is aminoacetonitrile, said primary aliphatic alkylamine is spermine or spermidine and said primary aliphatic lower-alkyl (C1-5) polyamine is putrescine or dansylcadaverine, and preferably putrescine. 
     
     
         4 . (canceled) 
     
     
         5 . The topical composition of  claim 3 , comprising between about 0.1% w/w and about 2% w/w of putrescine; or about 0.4% w/w of putrescine; or about 0.8% w/w or putrescine. 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . The topical composition of  claim 2 , wherein the at least one peptide is (i) tripeptide 1, (ii) tripeptide 5, (iii) tripeptide 10 citrulline, (iv) tetrapeptide 2, (v) acetylarginyltryptophyl diphenylglycine or any combination of at least two of (i) to (v). 
     
     
         18 . (canceled) 
     
     
         19 . The topical composition of  claim 2 , comprising at least one viscosity increasing agent/anticaking agent, wherein the at least one viscosity increasing agent/anticaking agent is magnesium aluminum silicate. 
     
     
         20 . (canceled) 
     
     
         21 . The topical composition of  claim 2 , comprising at least one binder/stabilizer, wherein the at least one binder/stabilizer is xanthan gum. 
     
     
         22 . (canceled) 
     
     
         23 . The topical composition of  claim 2 , comprising at least one skin conditioning agent, wherein the at least one skin conditioning agent is squalane. 
     
     
         24 . (canceled) 
     
     
         25 . The topical composition of  claim 2 , comprising at least one humectant, binder, emulsion stabilizer, surfactant and viscosity increasing agent, wherein the at least one at least one humectant, binder, emulsion stabilizer, surfactant and viscosity increasing agent is a blend of glyceryl stearate and PEG-100 stearate in a ratio of between about 4:6 and about 6:4 of glyceryl stearate: PEG-100 stearate. 
     
     
         26 . (canceled) 
     
     
         27 . The topical composition of  claim 2 , comprising at least one at least one rheology modifier, wherein the at least one rheology modifier is a blend of acrylates/acrylamide copolymer, mineral oil and polysorbate-85. 
     
     
         28 . The topical composition of  claim 1 , further comprising (a) at least one stabilizer which improves wet and dry compatibility and water resistance, wherein the concentration of the at least one stabilizer is between about 1% w/w and about 5% w/w; (b) hexamidine diisethionate as an antifoaming, skin conditioning, emollient and preservative agent; and/or (c) at least one antioxidant. 
     
     
         29 . The topical composition of  claim 28 , wherein the at least one stabilizer which improves wet and dry compatibility and water resistance is also a skin conditioning agent, emollient; moisturizer and solvent. 
     
     
         30 . The topical composition of  claim 29 , wherein the at least one stabilizer which improves wet and dry compatibility and water resistance is a blend of cyclopentasiloxane and dimethiconol. 
     
     
         31 . (canceled) 
     
     
         32 . The topical composition of  claim 28 , comprising about 0.1% w/w hexamidine diisethionate. 
     
     
         33 . (canceled) 
     
     
         34 . The topical composition of  claim 28 , wherein at least one antioxidant comprises a fruit extract, hydroquinone, a retinoid, resveratrol, tocopherol, tocopheryl acetate, retinol, retinyl palmitate, hydroquinone, proanthocyanidins, butylated hydroxytoluene, butylated hydroxyanisole, astaxanthin, alpha lipoic acid, tocotrienols, coenzyme Q10, α-hydroxy acid, kojic acid, kinetin, wine extract, vitamin K, a plant extract, resorcinol, lactic acid, salicylic acid or any combination of at least two thereof. 
     
     
         35 . The topical composition of  claim 1 , wherein the pH of the composition is between about 6.5 and about 7.5. 
     
     
         36 . The topical composition of  claim 1 , comprising at least 5 active ingredients; or at least 10 active ingredients; or at least 12 active ingredients. 
     
     
         37 . (canceled) 
     
     
         38 . (canceled) 
     
     
         39 . The topical composition of  claim 1 , comprising between about 55% and 65% w/w of water. 
     
     
         40 . A method of using the topical composition defined in  claim 1 , for (a) treating or preventing skin inflammation, skin irritation, and/or skin's signs of aging; (b) increasing skin thickness; (c) promoting wound healing; or (d) preventing or reducing the formation of hypertrophic scar tissue. 
     
     
         41 . (canceled) 
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . (canceled) 
     
     
         45 . (canceled) 
     
     
         46 . A process of preparing the composition defined in  claim 1 , comprising:
 (A)   
       (a) in a main tank:
 (ai) combining water and the at least one viscosity increasing agent/anticaking agent; 
 (aii) adding to the resulting mixture of (ai) the at least one binder/stabilizer; 
 (aiii) heating the resulting mixture of (aii) to about 65-70° C. and mixing until obtaining an homogenous mixture; 
 
       (b) in a separate tank, mixing
 (bi) the at least one humectant, binder, emulsion stabilizer, surfactant and viscosity increasing agent; 
 (bii) squalane; and 
 (biii) vitamin C, jojoba ester and/or vitamin E; and 
 heating to 65-70° C. and mixing until obtaining an homogenous mixture; 
 
       (c) adding the resulting mixture of (b) to (a) and mixing until homogenization; 
       (d) cooling the resulting mixture of (c) to about 50° C.; 
       (e) adding to (d) the rheology modifying agent and mixing until homogenization; 
       (f) cooling the resulting mixture of (e) to about 40° C.; 
       (g) in a separate tank, dissolving the primary polyamine (e.g., putrescine) in water (about 1-15% w/w, preferably about 5-15% w/w of water); and 
       (h) adding the resulting mixture of (g) to the resulting mixture of (f):
 (B) 
 
       (a) in a main tank:
 (ai) combining water and the at least one viscosity increasing agent/anticaking agent; 
 (aii) adding to the resulting mixture of (ai) the at least one binder/stabilizer; 
 (aiii) heating the resulting mixture of (aii) to about 65-70° C. and mixing until obtaining an homogenous mixture; 
 
       (b) in a separate tank, mixing (bi) the at least one humectant, binder, emulsion stabilizer, surfactant and viscosity increasing agent; and (bii) squalane; heating to 65ζ° C.; and mixing until obtaining an homogenous mixture; 
       (c) adding the resulting mixture of (b) to the resulting mixture of (a) and mixing until homogenization; 
       (d) cooling the resulting mixture of (c) to about 50° C.; 
       (e) adding the rheology modifying agent to the resulting mixture of (d) and mixing until homogenization; 
       (f) cooling the resulting mixture of (e) to about 40° C.; 
       (g) in a separate tank, dissolving putrescine in water (about 1-15% w/w, preferably about 5-15% w/w of water) and optionally adding a peptide; 
       (h) adding the resulting mixture of (g) to the resulting mixture of (f) and mixing until homogenization; and 
       (i) adding Vitamin C to the resulting mixture of (h) under mixing; or
 (C) 
 
       (a) in a main tank:
 (ai) combining water and the at least one viscosity increasing agent/anticaking agent; 
 (aii) adding to the resulting mixture of (ai) the at least one binder/stabilizer; 
 (aiii) heating the resulting mixture of (aii) to about 65-70° C. and mixing until obtaining a homogenous mixture; 
 
       (b) in a separate tank, mixing (bi) the at least one humectant, binder, emulsion stabilizer, surfactant and viscosity increasing agent; and (bii) squalane; heating to 65-70° C.; and mixing until obtaining an homogenous mixture; 
       (c) adding the resulting mixture of (b) to the resulting mixture of (a) and mixing until homogenization; 
       (d) cooling the resulting mixture of (c) to about 50° C.; 
       (e) in a separate tank, combining water with hexamidine diisethionate (about 1% w/w to about 3% w/w water), heating to about 75-80° C. and mixing until dissolved and clear; 
       (f) adding to the resulting mixture of (d) at least one further stabilizer (e.g., cyclopentasiloxane and dimethiconol) and the rheology modifier; 
       (g) in a separate container combining water (about 1% w/w to 5% w/w), Vitamin C, the primary polyamine (e.g., putrescine); heating to about 40° C. and mixing until homogenization; 
       (h) adding the resulting mixture of (g) to the resulting mixture of (f) under mixing at 40° C.; and
 combining the resulting mixture of (e) and the resulting mixture of (h) under mixing. 
 
     
     
         47 . (canceled) 
     
     
         48 . (canceled)