US2020237651A1PendingUtilityA1

Topical montelukast for treatment of atopic dermatitis

61
Assignee: TARO PHARMA INDPriority: May 4, 2016Filed: Jan 9, 2020Published: Jul 30, 2020
Est. expiryMay 4, 2036(~9.8 yrs left)· nominal 20-yr term from priority
A61K 9/0014A61K 31/495A61K 31/47A61K 31/00A61K 9/06A61K 45/06A61K 47/42A61K 47/20A61K 9/1075
61
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Claims

Abstract

A topical formulation comprising Montelukast or a pharmaceutically acceptable salt thereof, a gelling agent and water for the treatment of atopic dermatitis.

Claims

exact text as granted — not AI-modified
1 . A topical formulation comprising Montelukast or a pharmaceutically acceptable salt thereof, a gelling agent and water for the treatment of atopic dermatitis. 
     
     
         2 . The topical formulation of  claim 1 , wherein the concentration of Montelukast tor its pharmaceutically acceptable salt is between about 0.5% w/w to about 5% w/w or between about 5% w/w to about 10% w/w. 
     
     
         3 . The topical formulation of  claim 1 , wherein the concentration of montelukast or a pharmaceutically acceptable salt is 5% w/w. 
     
     
         4 . The topical formulation of  claim 1 , wherein between about 0.5% to about 1% of Montelukast is deposited within the skin following topical application. 
     
     
         5 . The topical formulation of  claim 1 , wherein the pH of the formulation is less than 6 
     
     
         6 . The topical formulation of  claim 1 , wherein the pH is in the range 5 to 6. 
     
     
         7 . The topical formulation of  claim 1 , wherein the formulation further comprises a water miscible organic solvent. 
     
     
         8 . The topical formulation of  claim 1 , wherein the formulation further comprises a penetration enhancer. 
     
     
         9 . The topical formulation of  claim 1 , wherein the formulation further comprises an antioxidant. 
     
     
         10 . The topical formulation of  claim 1 , wherein the formulation further comprises a preservative. 
     
     
         11 . The topical formulation of  claim 1  comprising:
 a) 
 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Category 
                   Ingredient 
                 
                     
                     
                 
                     
                   Active 
                   Montelukast sodium 
                 
                     
                   Water miscible 
                   Alcohol 96% 
                 
                     
                   organic solvent 
                 
                     
                   Penetration 
                   DMSO 
                 
                     
                   enhancer 
                 
                     
                   Antioxidant 
                   BHT 
                 
                     
                   Chelating Agent 
                   EDTA 
                 
                     
                   Water 
                   Purified water 
                 
                     
                   Preservative 
                   Methyl paraben 
                 
                     
                   Preservative 
                   Propyl paraben 
                 
                     
                   Gelling agent 
                   Hydroxyethylcellulose 
                 
                     
                     
                   (M w 90,000 to 1,300,000) 
                 
                     
                   pH adjusting 
                   HCl (10% solution) 
                 
                     
                   agent 
                 
                     
                     
                 
             
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         b) 
       
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Category of ingredient 
                   Example of Ingredient 
                 
                     
                     
                 
                     
                   Occlusive ingredient 
                   Dimethicone 
                 
                     
                   Occlusive ingredient 
                   Cyclomethicone 
                 
                     
                   Active 
                   Montelukast sodium 
                 
                     
                   Emulsifier 
                   Silicone Glycerol emulsifier 
                 
                     
                   Occlusive ingredient 
                   Cetearyl Ethylhexanoate 
                 
                     
                   Water miscible 
                   Glycerin 
                 
                     
                   organic solvent 
                 
                     
                   Solvent 
                   Water 
                 
                     
                   Gelling agent 
                   Sodium Carbomer 
                 
                     
                   Lubricant 
                   Sodium Hyaluronate 
                 
                     
                     
                 
             
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         c) 
       
       
         
           
                 
                 
               
                     
                 
                   Category of ingredient 
                   Example of Ingredient 
                 
                     
                 
                   Active 
                   Montelukast sodium 
                 
                   Water miscible 
                   Alcohol 
                 
                   organic solvent 
                 
                   Antioxidant 
                   BHT 
                 
                   Water 
                   Purified water 
                 
                   Penetration 
                   DMSO 
                 
                   enhancer 
                 
                   Preservative 
                   Methyl paraben 
                 
                   Preservative 
                   Propyl paraben 
                 
                   Gelling agent 
                   Carbopol 947P(polymers of acrylic acid) 
                 
                   Chelating agent 
                   EDTA 
                 
                   Emulsifier/ 
                   Sepineo 600(Acrylamide/Sodium 
                 
                   Thickener/Stabilizer 
                   Acryloyldimethyl Taurate copolymer/ 
                 
                     
                   isohexadecane and Polysorbate 80) 
                 
                     
                 
             
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         d) 
       
       
         
           
                 
                 
               
                     
                 
                   Category of ingredient 
                   Example of Ingredient 
                 
                     
                 
                   Active 
                   Montelukast sodium 
                 
                   Water miscible 
                   Alcohol 
                 
                   organic solvent 
                 
                   Antioxidant 
                   BHT 
                 
                   Water 
                   Purified water 
                 
                   Penetration 
                   DMSO 
                 
                   enhancer 
                 
                   Preservative 
                   Methyl paraben 
                 
                   Preservative 
                   Propyl paraben 
                 
                   Gelling agent 
                   Carbopol 947P(polymers of acrylic acid) 
                 
                   Chelating agent 
                   EDTA 
                 
                   Emulsifier/ 
                   Sepineo 600(Acrylamide/Sodium 
                 
                   Thickener/Stabilizer 
                   Acryloyldimethyl Taurate copolymer/ 
                 
                     
                   isohexadecane and Polysorbate 80) 
                 
                   pH adjusting 
                   Phosphate or citric acid Buffer 
                 
                   agent 
                 
                     
                 
             
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         12 . A topical formulation as in  claim 11  selected from any one of the following
 a) 
 
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                   Category 
                   Ingredient 
                   % W/W 
                 
                     
                     
                 
                     
                 
                 
                 
                 
                 
               
                     
                   Active 
                   Montelukast sodium 
                   5.00 
                 
                     
                   Water miscible 
                   Alcohol 96% 
                   25.00 
                 
                     
                   organic solvent 
                 
                     
                   Penetration 
                   DMSO 
                   10.00 
                 
                     
                   enhancer 
                 
                     
                   Antioxidant 
                   BHT 
                   0.10 
                 
                     
                   Chelating Agent 
                   EDTA 
                   0.10 
                 
                     
                   Water 
                   Purified water 
                   57.90 
                 
                     
                   Preservative 
                   Methyl paraben 
                   0.30 
                 
                     
                   Preservative 
                   Propyl paraben 
                   0.10 
                 
                     
                   Gelling agent 
                   Hydroxyethylcellulose 
                   1.50 
                 
                     
                     
                   (M w  90,000 to 1,300,000) 
                 
                     
                   pH adjusting 
                   HCl (10% solution) 
                   q.s. 
                 
                     
                   agent 
                 
                     
                     
                 
             
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         b) 
       
       
         
           
                 
                 
                 
               
                     
                 
                   Category of ingredient 
                   Ingredient 
                   % W/W 
                 
                     
                 
                     
                 
                 
                 
                 
               
                   Occlusive ingredient 
                   Dimethicone 
                   1 
                 
                   Occlusive ingredient 
                   Cyclomethicone 
                   4 
                 
                   Active 
                   Montelukast sodium 
                   3 
                 
                   Emulsifier 
                   Silicone Glycerol emulsifier 
                   1.5 
                 
                   Occlusive ingredient 
                   Cetearyl Ethylhexanoate 
                   2.5 
                 
                   Water miscible 
                   Glycerin 
                   3.0 
                 
                   organic solvent 
                 
                   Solvent 
                   Water 
                   Up to 100 
                 
                   Gelling agent 
                   Sodium Carbomer 
                   2.5 
                 
                   Lubricant 
                   Sodium Hyaluronate 
                   1.0 
                 
                     
                 
             
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         c) 
       
       
         
           
                 
                 
                 
               
                     
                 
                   Category of ingredient 
                   Ingredient 
                   % W/W 
                 
                     
                 
                   Active 
                   Montelukast sodium 
                     1% 
                 
                   Water miscible 
                   Alcohol 
                       25% 
                 
                   organic solvent 
                 
                   Antioxidant 
                   BHT 
                   0.10% 
                 
                   Water 
                   Purified water 
                   60.00 
                 
                   Penetration 
                   DMSO 
                   10.00%  
                 
                   enhancer 
                 
                   Preservative 
                   Methyl paraben 
                   0.30% 
                 
                   Preservative 
                   Propyl paraben 
                   0.10% 
                 
                   Gelling agent 
                   Carbopol 947P (polymers of acrylic 
                   0.40% 
                 
                     
                   acid) 
                 
                   Chelating agent 
                   EDTA 
                   0.10% 
                 
                   Emulsifier/ 
                   Sepineo 600(Acrylamide/Sodium 
                     3% 
                 
                   Thickener/Stabilizer 
                   Acryloyldimethyl Taurate copolymer/ 
                 
                     
                   isohexadecane and Polysorbate 80 
                 
                     
                 
             
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         d) 
       
       
         
           
                 
                 
                 
               
                     
                 
                   Category of ingredient 
                   Ingredient 
                   % W/W 
                 
                     
                 
                   Active 
                   Montelukast sodium 
                     1% 
                 
                   Water miscible organic solvent 
                   Alcohol 
                       25% 
                 
                   Antioxidant 
                   BHT 
                   0.10% 
                 
                   Water 
                   Purified water 
                   60.00 
                 
                   Penetration enhancer 
                   DMSO 
                   10.00%  
                 
                   Preservative 
                   Methyl paraben 
                   0.30% 
                 
                   Preservative 
                   Propyl paraben 
                   0.10% 
                 
                   Gelling agent 
                   Carbopol 947P 
                   0.40% 
                 
                     
                   (polymers of acrylic 
                 
                     
                   acid) 
                 
                   Chelating agent 
                   EDTA 
                   0.10% 
                 
                   Emulsifier/Thickener/Stabilizer 
                   Sepineo 600 
                     3% 
                 
                     
                   (Acrylamide/Sodium 
                 
                     
                   Acryloyldimethyl 
                 
                     
                   Taurate copolymer/ 
                 
                     
                   isohexadecane and 
                 
                     
                   Polysorbate 80 
                 
                   pH adjusting agent 
                   Phosphate Buffer 
                   pH 5.6 
                 
                     
                 
             
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         13 . The topical formulation of  claim 1 , wherein the montelukast is homogeneously suspended in the formulation or wherein montelukast crystals are present in the formulation. 
     
     
         14 . A topical formulation comprising Montelukast or a pharmaceutically acceptable salt thereof and at least one oil for the treatment of atopic dermatitis wherein the formulation is waterless. 
     
     
         15 . A topical formulation as in  claim 14  wherein the formulation further comprises a topically acceptable solvent, and an amphiphilic compound and further an occlusive ingredient 
     
     
         16 . A topical formulation as in  claim 15  selected from any of the following:
 a solution comprising 
 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Category of ingredient 
                   Example 
                 
                     
                     
                 
                     
                   Topically acceptable solvent 
                   Alcohol (Dehydrated) 
                 
                     
                   Amphiphilic compound 
                   Poloxylhydrogenated Castor oil 
                 
                     
                   Active 
                   Montelukast sodium 
                 
                     
                   Oil 
                   Fractionated Coconut oil 
                 
                     
                     
                 
             
                
                
                
               
               
                
                
                
                
                
               
            
           
         
         or a gel formulation comprising 
       
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Category of ingredient 
                   Example of ingredient 
                 
                     
                     
                 
                     
                   Topically acceptable solvent 
                   Alcohol (Dehydrated) 
                 
                     
                   Amphiphilic compound 
                   Poloxylhydrogenated Castor oil 
                 
                     
                   Active 
                   Montelukast sodium 
                 
                     
                   Oil 
                   Fractionated Coconut oil 
                 
                     
                   Gelling agent 
                   Hydroxypropylcellulose 
                 
                     
                     
                 
             
                
                
                
               
               
                
                
                
                
                
                
               
            
           
         
         or an ointment comprising 
       
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Category of ingredient 
                   Example of Ingredient 
                 
                     
                     
                 
                     
                   Active 
                   Montelukast sodium 
                 
                     
                   Occlusive ingredient 
                   Petroleum jelly/white petrolatum 
                 
                     
                   Oil 
                   Trihydroxystearin 
                 
                     
                   Oil 
                   Olive oil 
                 
                     
                     
                 
             
                
                
                
               
               
                
                
                
                
                
               
            
           
         
         or an ointment comprising 
       
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Category of ingredient 
                   Example of Ingredient 
                 
                     
                     
                 
                     
                   Active 
                   Montelukast sodium 
                 
                     
                   Water miscible organic solvent 
                   Glycerine 
                 
                     
                   Oil 
                   Medium chain triglycerides 
                 
                     
                   Antioxidant 
                   Antioxidant 
                 
                     
                     
                 
             
                
                
                
               
               
                
                
                
                
                
               
            
           
         
         or an ointment comprising 
       
       
         
           
                 
                 
               
                     
                 
                   Category of ingredient 
                   Example of Ingredient 
                 
                     
                 
                   Active 
                   Montelukast Sodium 
                 
                   Antioxidant 
                   BHT 
                 
                   Occlusive ingredient 
                   Cyclomethicone 5, NF 
                 
                   Occlusive ingredient 
                   Cyclomethicone and Dimethicone 5225C 
                 
                     
                 
             
                
                
                
               
               
                
                
                
                
                
               
            
           
         
         or an ointment comprising 
       
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Category of ingredient 
                   Example of Ingredient 
                 
                     
                     
                 
                     
                   Active 
                   Montelukast Sodium 
                 
                     
                   Antioxidant 
                   BHT 
                 
                     
                   Occlusive ingredient 
                   Petrolatum White USP 
                 
                     
                   Amphiphilic compound 
                   Propylene Glycol-15 Stearyl Ether 
                 
                     
                   Oil 
                   Medium Chain Triglycerides 
                 
                     
                   Amphiphilic compound 
                   Monosteol(propylene glycol 
                 
                     
                     
                   monostearate) 
                 
                     
                     
                 
             
                
                
                
               
               
                
                
                
                
                
                
                
                
               
            
           
         
         or an ointment comprising 
       
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Category of ingredient 
                   Example of Ingredient 
                 
                     
                     
                 
                     
                   Active 
                   Montelukast Sodium 
                 
                     
                   Antioxidant 
                   BHT 
                 
                     
                   Occlusive ingredient/ 
                   Petrolatum White USP 
                 
                     
                   Oil 
                   Mineral Oil 
                 
                     
                     
                 
             
                
                
                
               
               
                
                
                
                
                
               
            
           
         
       
     
     
         17 . A topical formulation as in  claim 16  selected from any one of the following:
 a solution comprising 
 
       
         
           
                 
                 
                 
               
                     
                 
                   Category of Ingredient 
                   Ingredient 
                   % W/W 
                 
                     
                 
                     
                 
                 
                 
                 
               
                   Topically acceptable 
                   Alcohol (Dehydrated) 
                   34.5 
                 
                   Amphiphilic compound 
                   Poloxylhydrogenated Castor 
                   2.5 
                 
                   Active 
                   Montelukast sodium 
                   3 
                 
                   oil 
                   Fractionated Coconut oil 
                   60 
                 
                     
                 
             
                
                
                
               
               
                
               
            
             
                
                
                
                
                
               
            
           
         
       
       or a gel formulation comprising 
       
         
           
                 
                 
                 
               
                     
                 
                   Category of ingredient 
                   Ingredient 
                   % W/W 
                 
                     
                 
                     
                 
                 
                 
                 
               
                   Topically acceptable solvent 
                   Alcohol (Dehydrated) 
                   31 
                 
                   Amphiphilic compound 
                   Poloxylhydrogenated Castor 
                   2.5 
                 
                   Active 
                   Montelukast sodium 
                   3 
                 
                   oil 
                   Fractionated Coconut oil 
                   60 
                 
                   Gelling agent 
                   Hydroxy propyl cellulose 
                   3.5 
                 
                     
                 
             
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
               
            
           
         
       
       or an ointment comprising 
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                   Category of 
                     
                     
                 
                     
                   ingredient 
                   Ingredient 
                   % W/W 
                 
                     
                     
                 
                     
                   Active 
                   Montelukast sodium 
                   0.5-5     
                 
                     
                   Occlusive 
                   Petroleum jelly/white 
                   80 
                 
                     
                   ingredient 
                   petrolatum 
                 
                     
                   Oil 
                   Trihydroxystcarin 
                   1-3 
                 
                     
                   oil 
                   Olive oil 
                       12-18.5 
                 
                     
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
               
            
           
         
       
       or an ointment comprising 
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                   Category of 
                     
                     
                 
                     
                   ingredient 
                   Ingredient 
                   % W/W{grave over ( )} 
                 
                     
                     
                 
                     
                   Active 
                   Montelukast sodium 
                   0.5-5     
                 
                     
                   Water miscible 
                   Glycerine 
                   65-75 
                 
                     
                   organic solvent 
                 
                     
                   Oil 
                   Medium chain 
                   20 
                 
                     
                     
                   triglycerides 
                 
                     
                   Antioxidant 
                   Antioxidant 
                       0-0.5 
                 
                     
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
                
               
            
           
         
       
       or an ointment comprising 
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                   Category of 
                     
                     
                 
                     
                   ingredient 
                   Ingredient 
                   % W/W{grave over ( )} 
                 
                     
                     
                 
                     
                 
                 
                 
                 
                 
               
                     
                   Active 
                   Montelukast Sodium 
                   5 
                 
                     
                   Antioxidant 
                   BHT 
                   0.08 
                 
                     
                   Occlusive 
                   Cyclomethicone 
                   94.52 
                 
                     
                   ingredient 
                 
                     
                   Amphiphilic 
                   Cyclomethicone and 
                   0.40 
                 
                     
                   compound 
                   Dimethicone 
                 
                     
                     
                 
             
                
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
               
            
           
         
       
       or an ointment comprising 
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                   Category of 
                     
                     
                 
                     
                   ingredient 
                   Ingredient 
                   % W/W{grave over ( )} 
                 
                     
                     
                 
                     
                 
                 
                 
                 
                 
               
                     
                   Active 
                   Montelukast Sodium 
                   5 
                 
                     
                   Antioxidant 
                   BHT 
                   0.08 
                 
                     
                   Occlusive 
                   Petrolatum White 
                   55.92 
                 
                     
                   ingredient 
                 
                     
                   Amphiphilic 
                   PPG-15 Stearyl Ether 
                   16 
                 
                     
                   compound 
                 
                     
                   Oil 
                   Medium Chain Triglycerides 
                   20 
                 
                     
                   Amphiphilic 
                   Monosteol 
                   3 
                 
                     
                   compound 
                 
                     
                     
                 
             
                
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       or an ointment comprising 
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                   Category of 
                     
                     
                 
                     
                   ingredient 
                   Ingredient 
                   % W/W{grave over ( )} 
                 
                     
                     
                 
                     
                 
                 
                 
                 
                 
               
                     
                   Active 
                   Montelukast Sodium 
                   5 
                 
                     
                   Antioxidant 
                   BHT 
                   0.08 
                 
                     
                   Occlusive 
                   Petrolatum White 
                   49.92 
                 
                     
                   ingredient/ 
                 
                     
                   Oil 
                   Mineral Oil 
                   45

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