Retinoid compositions containing a water soluble antioxidant and a chelator

Abstract

Skin care compositions comprising a water-in-oil emulsion base containing retinoids and possessing good physical and chemical stability.

1. A skin care composition comprising a water-in-oil emulsion and a retinoid selected from the group consisting of Vitamin A alcohol, Vitamin A aldehyde, retinyl acetate, retinyl palmitate and mixtures thereof, said composition further comprising a stabilizing system comprising a chelating agent and at least one water-soluble antioxidant said composition retaining at least about 60% by weight of said retinoid after 13 weeks storage at 40° C. 
     
     
       2. The skin care composition of  claim 1  wherein the retinoid is Vitamin A alcohol. 
     
     
       3. The skin care composition of  claim 1  wherein the water-soluble antioxidant is selected from the group consisting of ascorbic acid, sodium sulfite, sodium metabisulfite, sodium bisulfite, sodium thiosulfite, sodium formaldehyde sulfoxylate, isoascorbic acid, thioglycerol, thiosorbitol, thiourea, thioglycolic acid, cysteine hydrochloride, 1,4-diazobicyclo-(2,2,2)-octane and mixtures thereof. 
     
     
       4. The skin care composition of  claim 3  wherein the water-soluble antioxidant is selected from the group consisting of ascorbic acid, sodium bisulfite, sodium metabisulfite, thioglycerol, sodium formaldehyde sulfoxylate and 1,4-diazobicycle-(2,2,2,)-octane and mixtures thereof. 
     
     
       5. The skin care composition of  claim 4  wherein the water-soluble antioxidant is ascorbic acid. 
     
     
       6. The skin care composition of  claim 1  wherein the chelating agent is selected from the group consisting of ethylenediamine tetracetic acid (EDTA) and derivatives and salts thereof, dihydroxyethyl glycine, citric acid, tartaric acid, and mixtures thereof. 
     
     
       7. The skin care composition of  claim 6  wherein the chelating agent is selected from the group consisting of ethylenediamine tetracetic acid and derivatives and salts thereof. 
     
     
       8. A skin care composition comprising a water-in-oil emulsion and a retinoid selected from the group consisting of retinol, retinal, retinyl acetate, retinyl palmitate and mixtures thereof, said composition further comprising a stabilizing system comprising a chelating agent and at least one water-soluble antioxidant, said composition retaining at least about 60% of said retinoid after 13 weeks storage at 40° C. 
     
     
       9. The skin care composition of  claim 8  wherein the retinoid is Vitamin A alcohol. 
     
     
       10. The skin care composition of  claim 8  wherein the water-soluble antioxidant is selected from the group consisting of ascorbic acid, sodium sulfite, sodium metabisulfite, sodium bisulfite, sodium thiosulfite, sodium formaldehyde sulfoxylate, isoascorbic acid, thioglycerol, thiosorbitol, thiourea, thioglycolic acid, cysteine hydrochloride, 1,4-diazobicyclo-(2,2,2)-octane and mixtures thereof. 
     
     
       11. The skin care composition of  claim 10  wherein the water-soluble antioxidant is selected from the group consisting of ascorbic acid, sodium bisulfite, sodium metabisulfite, thioglycerol, sodium formaldehyde sulfoxylate and 1,4-diazobicyclo-(2,2,2,)-octane and mixtures thereof. 
     
     
       12. The skin care composition of  claim 11  wherein the water-soluble antioxidant is ascorbic acid. 
     
     
       13. The skin care composition of  claim 10  wherein the chelating agent is selected from the group consisting of ethylenediamine tetracetic acid (EDTA) and derivatives and salts thereof, dihydroxyethyl glycine, citric acid, tartaric acid, and mixtures thereof. 
     
     
       14. The skin care composition of  claim 13  wherein the chelating agent is selected from the group consisting of ethylenediamine tetracetic acid and derivatives and salts thereof. 
     
     
       15. The skin care composition of  claim 10  wherein said stabilizing system comprises a chelating agent and antioxidant present in each of the oil and water phases of said emulsion. 
     
     
       16. A method for manufacturing an emulsion skin care composition that comprises a water phase, an oil phase, a retinoid selected from the group consisting of Vitamin A alcohol, Vitamin A aldehyde, retinyl acetate, retinyl palmitate and mixtures thereof, and a stabilizing system selected from the group consisting of:
 ( i )  a stabilizing system comprising a chelating agent and at least one water - soluble antioxidant,      ( ii )  a stabilizing system comprising a chelating agent and at least one oil - soluble antioxidant, and      ( iii )  a stabilizing system comprising at least one water - soluble antioxidant and at least one oil - soluble antioxidant, said method, comprising the steps of:  
 (   1   )  preparing the oil phase including oil - soluble components of the stabilizing system;    
 (   2   )  preparing the water phase including water - soluble components of the stabilizing system;    
 (   3   )  combining the oil phase and the water phase to form an emulsion; and    
 (   4   )  adding said retinoid to said emulsion in the presence of an oxygen depleted atmosphere to produce an emulsion skin care composition that comprises an oil phase, a water phase, a retinoid and a stabilizing system.    
   
     
     
       17. The method of  claim 16 , wherein one or more of steps (   1   ) ,  (   2   )  and  (   3   )  are performed in an oxygen depleted atmosphere.    
     
     
       18. The method of  claim 16 , wherein each of steps (   1   ) ,  (   2   )  and  (   3   )  are performed in an oxygen depleted atmosphere.    
     
     
       19. The method of  claim 16 , wherein the retinoid is retinol.  
     
     
       20. The method of  claim 16 , wherein the oxygen depleted atmosphere is obtained by operating under vacuum conditions.  
     
     
       21. The method of  claim 16 , wherein the oxygen depleted atmosphere comprises argon or nitrogen.  
     
     
       22. The method of  claim 16 , wherein the oxygen depleted atmosphere comprises argon.  
     
     
       23. The method of  claim 16 , wherein the retinoid is added to the emulsion in the absence of ultraviolet light.  
     
     
       24. The method of  claim 16 , wherein said composition retaining at least about  60 %  of said retinoid after  13  weeks storage at  40 ° C.    
     
     
       25. The method of  claim 16 , wherein the pH of said composition is between about  4  to about  7 .  
     
     
       26. The method of  claim 16 , wherein said oil phase and said water phase are each heated until all of the ingredients of said phases are substantially liquefied.  
     
     
       27. A method of  claim 16 , wherein:
 ( a )  the preparation of the oil phase comprises heating oil phase to above about  40 ° C.;      ( b )  the preparation of the water phase comprises heating the water phase to above about  40 ° C.; and      ( c )  the emulsion formed by combining the oil phase and the water phase is allowed to cool prior to the addition of the retinoid.      
     
     
       28. The method of  claim 27 , wherein said water phase is heated to above  75 ° C., said oil phase is heated to above about  80 ° C., and said retinoid is added after the emulsion has cooled to below about  53 ° C.  
     
     
       29. The method of  claim 16 , further comprising the step of inserting said emulsion into containers in the presence of argon.  
     
     
       30. The method of  claim 29 , wherein said container is a capped tube.  
     
     
       31. The method of  claim 16 , wherein said emulsion is a water- in - oil emulsion.    
     
     
       32. The method of  claim 16 , wherein the stabilizing system comprises a chelating agent and at least one water- soluble antioxidant.    
     
     
       33. The method of  claim 32 , wherein said water- soluble antioxidant is selected from the group consisting of ascorbic acid, sodium sulfite, sodium metabisulfite, sodium bisulfate, sodium thiosulfite, sodium formaldehyde sulfoxylate, isoascorbic acid, thioglycerol, thiosorbitol, thiourea, thioglycolic acid, cysteine hydrochloride,  1 , 4   - diazobicyclo -(   2 , 2 , 2   )- octane and mixtures thereof.    
     
     
       34. The method of  claim 32 , wherein said chelating agent is selected from the group consisting of ethylenediamine tetracetic acid and derivatives and salts thereof, dihydroxyethyl glycine, citric acid, tartaric acid, and mixtures thereof.  
     
     
       35. The method of  claim 16 , wherein the stabilizing system comprises a chelating agent and at least one oil- soluble antioxidant.    
     
     
       36. The method of  claim 35 , wherein said oil- soluble antioxidant is selected from the group consisting of butylated hydroxytoluene, ascorbyl palmitate, butylated hydroxyanisole, alpha - tocopherol, phenyl - alpha - naphthylamine, hydroquinone, propyl gallate, nordihydroguiaretic acid, and mixtures thereof.    
     
     
       37. The method of  claim 35 , wherein said chelating agent is selected from the group consisting of ethylenediamine tetracetic acid and derivatives and salts thereof, dihydroxyethyl glycine, citric acid, tartaric acid, and mixtures thereof.  
     
     
       38. The method of  claim 35 , wherein the stabilizing system further comprises at least one water- soluble antioxidant.    
     
     
       39. The method of  claim 38 , wherein said water- soluble antioxidant is selected from the group consisting of ascorbic acid, sodium sulfite, sodium metabisulfite, sodium bisulfate, sodium thiosulfite, sodium formaldehyde sulfoxylate, isoascorbic acid, thioglycerol, thiosorbitol, thiourea, thioglycolic acid, cysteine hydrochloride,  1 , 4   - diazobicyclo -(   2 , 2 , 2   )- octane and mixtures thereof.    
     
     
       40. The method of  claim 35 , wherein one or more of steps (   1   ) ,  (   2   )  and  (   3   )  are performed in an oxygen depleted atmosphere.    
     
     
       41. The method of  claim 35 , wherein each of steps (   1   ) ,  (   2   )  and  (   3   )  are performed in an oxygen depleted atmosphere.    
     
     
       42. The method of  claim 35 , wherein the retinoid is retinol.  
     
     
       43. The method of  claim 35 , wherein the oxygen depleted atmosphere is obtained by operating under vacuum conditions.  
     
     
       44. The method of  claim 35 , wherein the oxygen depleted atmosphere comprises argon or nitrogen.  
     
     
       45. The method of  claim 35 , wherein the oxygen depleted atmosphere comprises argon.  
     
     
       46. The method of  claim 35 , wherein the retinoid is added to the emulsion in the absence of ultraviolet light.  
     
     
       47. The method of  claim 35 , wherein said composition retaining at least about  60 %  of said retinoid after  13  weeks storage at  40 ° C.    
     
     
       48. The method of  claim 35 , wherein the pH of said composition is between about  4  to  7 .  
     
     
       49. The method of  claim 35 , wherein said oil phase and said water phase are each heated until all of the ingredients of said phases are substantially liquefied.  
     
     
       50. A method of  claim 35 , wherein:
 ( a )  the preparation of the oil phase comprises heating it to above about  40 ° C.;      ( b )  the preparation of the water phase comprises heating it to above about  40 ° C.; and      ( c )  the emulsion formed by combining the oil phase and the water phase is allowed to cool prior to the addition of the retinoid.      
     
     
       51. The method of  claim 50 , wherein said water phase is heated to above  75 ° C., said oil phase is heated to above about  80 ° C., and said retinoid is added after the emulsion has cooled to below about  53 ° C.  
     
     
       52. The method of  claim 35 , further comprising the step of inserting said emulsion into containers in the presence of argon.  
     
     
       53. The method of  claim 52 , wherein said container is a capped tube.  
     
     
       54. The method of  claim 35 , wherein said emulsion is a water- in - oil emulsion.    
     
     
       55. The method of  claim 16 , wherein the stabilizing system comprises at least one water- soluble antioxidant and at least one oil - soluble antioxidant.    
     
     
       56. The method of  claim 55 , wherein said water- soluble antioxidant is selected from the group consisting of ascorbic acid, sodium sulfite, sodium metabisulfite, sodium bisulfate, sodium thiosulfite, sodium formaldehyde sulfoxylate, isoascorbic acid, thioglycerol, thiosorbitol, thiourea, thioglycolic acid, cysteine hydrochloride,  1 , 4   - diazobicyclo -(   2 , 2 , 2   )- octane and mixtures thereof.    
     
     
       57. The method of  claim 55 , wherein said oil- soluble antioxidant is selected from the group consisting of butylated hydroxytoluene, ascorbyl palmitate, butylated hydroxyanisole, alpha - tocopherol, phenyl - alpha - naphthylamine, hydroquinone, propyl gallate, nordihydroguiaretic acid, and mixtures thereof.    
     
     
       58. A method for manufacturing an emulsion skin care composition comprising a water phase, an oil phase, a retinoid selected from the group consisting of Vitamin A alcohol, Vitamin A aldehyde, retinyl acetate, retinyl palmitate and mixtures thereof, and a stabilizing system selected from the group consisting of:
 ( i )  a stabilizing system comprising a chelating agent and at least one water - soluble antioxidant;      ( ii )  a stabilizing system comprising a chelating agent and at least one oil - soluble antioxidant; and      ( iii )  a stabilizing system comprising at least one water - soluble antioxidant and at least one oil - soluble antioxidant;      
       
         said method comprising the steps of:  
         (   1   )  preparing the oil phase including the retinoid and oil - soluble components of the stabilizing system in the presence of an oxygen depleted atmosphere;    
         (   2   )  preparing the water phase including water - soluble components of the stabilizing system; and    
         (   3   )  combining the oil phase and the water phase in the presence of an oxygen depleted atmosphere to form an emulsion skin care composition that comprises an oil phase, a water phase, a retinoid and a stabilizing system.    
       
     
     
       59. The method of  claim 58 , wherein step (   2   )  is performed in an oxygen depleted atmosphere.    
     
     
       60. The method of  claim 58 , wherein the retinoid is retinol.  
     
     
       61. The method of  claim 58 , wherein the oxygen depleted atmosphere is obtained by operating under vacuum conditions.  
     
     
       62. The method of  claim 58 , wherein the oxygen depleted atmosphere comprises argon or nitrogen.  
     
     
       63. The method of  claim 58 , wherein the oxygen depleted atmosphere comprises argon.  
     
     
       64. The method of  claim 58 , wherein the retinoid is added to the oil phase in the absence of ultraviolet light.  
     
     
       65. The method of  claim 58 , wherein said composition retaining at least about  60 %  of said retinoid after  13  weeks storage at  40 ° C.    
     
     
       66. The method of  claim 58 , wherein the pH of said composition is between about  4  to about  7 .  
     
     
       67. The method of  claim 58 , wherein said oil phase and said water phase are each heated until all of the ingredients of said phases are substantially liquefied.  
     
     
       68. A method of  claim 58 , wherein:
 ( a )  the preparation of the oil phase comprises heating it to above about  40 ° C.; and      ( b )  the preparation of the water phase comprises heating it to above about  40 ° C.      
     
     
       69. The method of  claim 58 , further comprising the step of inserting said emulsion into containers in the presence of argon.  
     
     
       70. The method of  claim 69 , wherein said container is a capped tube.  
     
     
       71. The method of  claim 58 , wherein said emulsion is a water- in - oil emulsion.    
     
     
       72. The method of  claim 58 , wherein the stabilizing system comprises a chelating agent and at least one water- soluble antioxidant.    
     
     
       73. The method of  claim 72 , wherein said water- soluble antioxidant is selected from the group consisting of ascorbic acid, sodium sulfite, sodium metabisulfite, sodium bisulfate, sodium thiosulfite, sodium formaldehyde sulfoxylate, isoascorbic acid, thioglycerol, thiosorbitol, thiourea, thioglycolic acid, cysteine hydrochloride,  1 , 4   - diazobicyclo -(   2 , 2 , 2   )- octane and mixtures thereof.    
     
     
       74. The method of  claim 72 , wherein said chelating agent is selected from the group consisting of ethylenediamine tetracetic acid and derivatives and salts thereof, dihydroxyethyl glycine, citric acid, tartaric acid, and mixtures thereof.  
     
     
       75. The method of  claim 58 , wherein the stabilizing system comprises a chelating agent and at least one oil- soluble antioxidant.    
     
     
       76. The method of  claim 75 , wherein said oil- soluble antioxidant is selected from the group consisting of butylated hydroxytoluene, ascorbyl palmitate, butylated hydroxyanisole, alpha - tocopherol, phenyl - alpha - naphthylamine, hydroquinone, propyl gallate, nordihydroguiaretic acid; and mixtures thereof.    
     
     
       77. The method of  claim 75 , wherein said chelating agent is selected from the group consisting of ethylenediamine tetracetic acid and derivatives and salts thereof, dihydroxyethyl glycine, citric acid, tartaric acid, and mixtures thereof.  
     
     
       78. The method of  claim 75 , wherein the stabilizing system further comprises at least one water- soluble antioxidant.    
     
     
       79. The method of  claim 78 , wherein said water- soluble antioxidant is selected from the group consisting of ascorbic acid, sodium sulfite, sodium metabisulfite, sodium bisulfate, sodium thiosulfite, sodium formaldehyde sulfoxylate, isoascorbic acid, thioglycerol, thiosorbitol, thiourea, thioglycolic acid, cysteine hydrochloride,  1 , 4   - diazobicyclo -(   2 , 2 , 2   )- octane and mixtures thereof.    
     
     
       80. The method of  claim 75 , wherein step (   2   )  is performed in an oxygen depleted atmosphere.    
     
     
       81. The method of  claim 75 , wherein the retinoid is retinol.  
     
     
       82. The method of  claim 75 , wherein the oxygen depleted atmosphere is obtained by operating under vacuum conditions.  
     
     
       83. The method of  claim 75 , wherein the oxygen depleted atmosphere comprises argon or nitrogen.  
     
     
       84. The method of  claim 75 , wherein the oxygen depleted atmosphere comprises argon.  
     
     
       85. The method of  claim 75 , wherein the retinoid is added to the emulsion in the absence of ultraviolet light.  
     
     
       86. The method of  claim 75 , wherein said composition retaining at least about  60 %  of said retinoid after  13  weeks storage at  40 ° C.    
     
     
       87. The method of  claim 75 , wherein the pH of said composition is between about  4  to about  7 .  
     
     
       88. The method of  claim 75 , wherein said oil phase and said water phase are each heated until all of the ingredients of said phases are substantially liquefied.  
     
     
       89. A method of  claim 75 , wherein:
 ( a )  the preparation of the oil phase comprises heating it to above about  40 ° C.; and      ( b )  the preparation of the water phase comprises heating it to above about  40 ° C.      
     
     
       90. The method of  claim 75 , further comprising the step of inserting said emulsion into containers in the presence of argon.  
     
     
       91. The method of  claim 90 , wherein said container is a capped tube.  
     
     
       92. The method of  claim 75 , wherein said emulsion is a water- in - oil emulsion.    
     
     
       93. The method of  claim 58 , wherein the stabilizing system comprises at least one water- soluble antioxidant and at least one oil - soluble antioxidant.    
     
     
       94. The method of  claim 93 , wherein said water- soluble antioxidant is selected from the group consisting of ascorbic acid, sodium sulfite, sodium metabisulfite, sodium bisulfate, sodium thiosulfite, sodium formaldehyde sulfoxylate, isoascorbic acid, thioglycerol, thiosorbitol, thiourea, thioglycolic acid, cysteine hydrochloride,  1 , 4   - diazobicyclo -(   2 , 2 , 2   )- octane and mixtures thereof.    
     
     
       95. The method of  claim 93 , wherein said oil- soluble antioxidant is selected from the group consisting of butylated hydroxytoluene, ascorbyl palmitate, butylated hydroxyanisole, alpha - tocopherol, phenyl - alpha - naphthylamine, hydroquinone, propyl gallate, nordihydroguiaretic acid, and mixtures thereof.