Composition and method for treating skin conditions

Abstract

Compositions and methods for treatment of conditions affecting skin and/or mucosal surfaces of a subject that make use of an imidazoquinoline compound and a retinoid agent are described.

1 . A composition, comprising:
 an imidazoquinoline compound; and   a retinoid agent.   
     
     
         2 . The composition of  claim 1 , wherein the imidazoquinoline compound is selected from the group consisting of: imiquimod, resiquimod, and sotirimod. 
     
     
         3 . The composition of  claim 1 , wherein the imidazoquinoline compound is imiquimod. 
     
     
         4 . The composition of  claim 3 , wherein the retinoid agent is selected from the group consisting of: retinol, retinal, retinyl acetate, retinaldehyde, retinyl palmitate, retinoic acid, retinyl propionate, retinyl linoleate, dehydroretinol, eretinate, eretrin, motretinide, tazarotene, isotretinoin, tretinoin, adapalene, bexarotene, fenretinide, and alitretinoin. 
     
     
         5 . The composition of  claim 1 , wherein the retinoid agent is selected from the group consisting of: retinol, retinal, retinyl acetate, retinaldehyde, retinyl palmitate, retinoic acid, retinyl propionate, retinyl linoleate, dehydroretinol, eretinate, eretrin, motretinide, tazarotene, isotretinoin, tretinoin, adapalene, bexarotene, fenretinide, and alitretinoin. 
     
     
         6 . The composition of  claim 1 , wherein the retinoid agent is tazarotene. 
     
     
         7 . The composition of  claim 1 , wherein the imidazoquinoline compound is selected from the group consisting of: imiquimod, resiquimod, and sotirimod; and the retinoid agent is selected from the group consisting of: retinol, retinal, retinyl acetate, retinaldehyde, retinyl palmitate, retinoic acid, retinyl propionate, retinyl linoleate, dehydroretinol, eretinate, eretrin, motretinide, tazarotene, isotretinoin, tretinoin, adapalene, bexarotene, fenretinide, and alitretinoin. 
     
     
         8 . The composition of  claim 1 , wherein the imidazoquinoline compound is imiquimod and the retinoid agent is tazarotene. 
     
     
         9 . The composition of  claim 8 , and further comprising one or more ingredient selected from the group consisting of: salicylic acid, urea, an alpha hydroxyl acid, and a beta hydroxyl acid. 
     
     
         10 . The composition of  claim 8 , and further comprising salicylic acid. 
     
     
         11 . The composition of  claim 1 , and further comprising one or more ingredient selected from the group consisting of: salicylic acid, urea, an alpha hydroxyl acid, and a beta hydroxyl acid. 
     
     
         12 . The composition of  claim 1 , and further comprising salicylic acid. 
     
     
         13 . The composition of  claim 1 , wherein the composition is provided for the treatment of a condition affecting the skin and/or mucosal surfaces of a subject. 
     
     
         14 . The composition of  claim 13 , wherein the condition is selected from a wart,  molluscum contagiosum,  a keloid, and a skin cancer. 
     
     
         15 . The composition of  claim 13 , wherein the condition is a wart. 
     
     
         16 . The composition of  claim 15 , wherein the wart is caused by a papillomavirus. 
     
     
         17 . The composition of  claim 15 , wherein the wart is caused by a human papollomaviruses (HPV). 
     
     
         18 . The composition of  claim 15 , wherein the wart is selected from:  verruca vulgaris  (common wart),  verruca plana  (flat wart)  condyloma acuminatum  or  verruca acuminate  (genital wart), and  verruca pedis  (plantar wart). 
     
     
         19 . The composition of  claim 13 , wherein the condition is  Molluscum contagiosum.    
     
     
         20 . The composition of  claim 13 , wherein the condition is a keloid scar. 
     
     
         21 . The composition of  claim 13 , wherein the condition is a hypertrophic scar. 
     
     
         22 . The composition of  claim 13 , wherein the condition is a skin cancer. 
     
     
         23 . The composition of  claim 22 , wherein the skin cancer is a premalignant skin cancer. 
     
     
         24 . The composition of  claim 22 , wherein the skin cancer is a malignant skin cancer. 
     
     
         25 . The composition of  claim 22 , wherein the skin cancer is selected from melanoma and non-melanoma skin cancers, actinic keratoses, basal cell carcinomas, squamous cell carcinoma-in-situ or Bowen's disease, melanoma in-situ, and other unresectable carcinomas. 
     
     
         26 . The composition of  claim 22 , wherein the skin cancer is actinic keratoses. 
     
     
         27 . The composition of  claim 22 , wherein the skin cancer is a primary skin cancer. 
     
     
         28 . The composition of  claim 22 , wherein the skin cancer is a secondary skin cancer. 
     
     
         29 . The composition of  claim 22 , wherein the skin cancer is selected from: cutaneous T-cell lymphoma, extramammary Paget's disease, lentigo maligna, cutaneous melanoma metastases, and cutaneous leishmaniasis. 
     
     
         30 . The composition of  claim 13 , wherein the condition is affecting a mucosal surface of the subject. 
     
     
         31 . The composition of  claim 13 , wherein the subject is a human. 
     
     
         32 . The composition of  claim 13 , wherein the subject is a transplant patient. 
     
     
         33 . The composition of  claim 13 , wherein the subject is receiving antirejection therapy following a transplant. 
     
     
         34 . The composition of  claim 1 , wherein the retinoid agent is provided in the composition at a final concentration between about 1% (wt/wt) and about 0.001% (wt/wt). 
     
     
         35 . The composition of  claim 1 , wherein the retinoid agent is provided in the composition at a final concentration between about 1% (wt/wt) and about 0.001% (wt/wt). 
     
     
         36 . The composition of  claim 1 , wherein the retinoid agent is provided in the composition at a final concentration between about 1% (wt/wt) and about 0.025% (wt/wt). 
     
     
         37 . The composition of  claim 1 , wherein the retinoid agent is provided in the composition at a final concentration between about 0.5% (wt/wt) and about 0.01% (wt/wt). 
     
     
         38 . The composition of  claim 1 , wherein the retinoid agent is tazarotene provided in the composition at a final concentration between about 1% (wt/wt) and about 0.001% (wt/wt). 
     
     
         39 . The composition of  claim 38 , wherein the tazarotene is provided in the composition at a final concentration between about 1% (wt/wt) and about 0.001% (wt/wt). I 
     
     
         40 . The composition of  claim 38 , wherein the tazarotene is provided in the composition at a final concentration between about 1% (wt/wt) and about 0.025% (wt/wt). 
     
     
         41 . The composition of  claim 38 , wherein the tazarotene is provided in the composition at a final concentration between about 0.5% (wt/wt) and about 0.01% (wt/wt). 
     
     
         42 . The composition of  claim 38 , wherein the tazarotene is provided at a concentration of about 1% (wt/wt). 
     
     
         43 . The composition of  claim 38 , wherein the tazarotene is provided at a concentration of about 0.5% (wt/wt). 
     
     
         44 . The composition of  claim 38 , wherein the tazarotene is provided at a concentration of about 0.1% (wt/wt). 
     
     
         45 . The composition of  claim 38 , wherein the tazarotene is provided at a concentration of about 0.05% (wt/wt). 
     
     
         46 . The composition of  claim 38 , wherein the tazarotene is provided at a concentration of about 0.01% (wt/wt). 
     
     
         47 . The composition of  claim 38 , wherein the tazarotene is provided at a concentration of about 0.005% (wt/wt). 
     
     
         48 . The composition of  claim 38 , wherein the tazarotene is provided at a concentration of about 0.001% (wt/wt). 
     
     
         49 . The composition of  claim 1 , wherein the imidazoquinoline compound is provided in the composition at a final concentration between about 10% (wt/wt) and about 0.1% (wt/wt). 
     
     
         50 . The composition of  claim 1 , wherein the imidazoquinoline compound is provided in the composition at a final concentration between about 7% (wt/wt) and about 3% (wt/wt). 
     
     
         51 . The composition of  claim 1 , wherein the imidazoquinoline compound is imiquimod provided in the composition at a final concentration between about 10% (wt/wt) and about 0.1% (wt/wt). 
     
     
         52 . The composition of  claim 51 , wherein the imiquimod is provided in the composition at a final concentration between about 7% (wt/wt) and about 3% (wt/wt). 
     
     
         53 . The composition of  claim 51 , wherein the imiquimod is provided at a concentration of about 10% (wt/wt). 
     
     
         54 . The composition of  claim 51 , wherein the imiquimod is provided at a concentration of about 5% (wt/wt). 
     
     
         55 . The composition of  claim 51 , wherein the imiquimod is provided at a concentration of about 3.75% (wt/wt). 
     
     
         56 . The composition of  claim 51 , wherein the imiquimod is provided at a concentration of about 1% (wt/wt). 
     
     
         57 . The composition of  claim 51 , wherein the imiquimod is provided at a concentration of about 0.5% (wt/wt). 
     
     
         58 . The composition of  claim 51 , wherein the imiquimod is provided at a concentration of about 0.1% (wt/wt). 
     
     
         59 . The composition of  claim 1 , wherein composition allows for increased penetration of the imidazoquinoline compound. 
     
     
         60 . The composition of  claim 1 , wherein the composition including a combination of the imidazoquinoline compound and the retinoid agent has a synergistic effect. 
     
     
         61 . The composition of  claim 1 , wherein the imidazoquinoline compound and the retinoid agent are provided in formulation that includes a solvent. 
     
     
         62 . The composition of  claim 61 , wherein the imidazoquinoline compound is imiquimod and the retinoid agent is tazarotene. 
     
     
         63 . The composition of  claim 62 , wherein the solvent includes isostearic acid. 
     
     
         64 . The composition of  claim 63 , wherein the solvent further includes alcohol, diethyl sebacate, or mineral oil. 
     
     
         65 . The composition of  claim 1 , wherein the composition is substantially stable at a temperature of 50° C. for a period of four (4) weeks. 
     
     
         66 . The composition of  claim 1 , wherein the composition is substantially stable at a temperature of 40° C. for a period of four (4) weeks. 
     
     
         67 . The composition of  claim 1 , wherein the composition is substantially stable at a temperature of 25° C. for a period of four (4) weeks. 
     
     
         68 . The composition of  claim 1 , wherein the composition is substantially stable following up to three freeze/warm cycles from −20° C. to 40° C. 
     
     
         69 . The composition of  claim 1 , wherein the composition is formulated for topical delivery. 
     
     
         70 . The composition of  claim 1 , wherein the imidazoquinoline compound is imiquimod provided in the composition at a final concentration between about 10% (wt/wt) and about 0.1% (wt/wt); the retinoid agent is tazarotene provided in the composition at a final concentration between about 1% (wt/wt) and about 0.001% (wt/wt); and the composition is substantially stable at a temperature of 25° C. for a period of four (4) weeks. 
     
     
         71 . The composition of  claim 66 , wherein the composition is substantially stable at a temperature of 50° C. for a period of four (4) weeks. 
     
     
         72 . A pharmaceutical composition of  claim 1 . 
     
     
         73 . A kit, comprising: a composition of  claim 1 , and a device useful for administration of the composition. 
     
     
         74 . The kit of  claim 68 , wherein the device is selected from the group consisting of: a stick, tape, an occlusive applicator, and an occlusive bandage. 
     
     
         75 . A method for the treatment of a condition affecting skin and/or a mucosal surface of a subject, comprising: administering an effective amount of a composition comprising an imidazoquinoline compound and a retinoid agent to the subject. 
     
     
         76 . The method of  claim 75 , wherein the composition is administered to an affected site on the skin and/or mucosal surface of the subject. 
     
     
         77 . The method of  claim 75 , wherein the composition is administered topically. 
     
     
         78 . The method of  claim 75 , wherein the composition is administered by intralegional injection. 
     
     
         79 . The method of  claim 75 , wherein the imidazoquinoline compound is selected from the group consisting of: imiquimod, resiquimod, and sotirimod; and the retinoid agent is selected from the group consisting of: retinol, retinal, retinyl acetate, retinaldehyde, retinyl palmitate, retinoic acid, retinyl propionate, retinyl linoleate, dehydroretinol, eretinate, eretrin, motretinide, tazarotene, isotretinoin, tretinoin, adapalene, bexarotene, fenretinide, and alitretinoin. 
     
     
         80 . The method of  claim 75 , wherein the retinoid agent is tazarotene. 
     
     
         81 . The method of  claim 75 , wherein the imidazoquinoline compound is imiquimod. 
     
     
         82 . The method of  claim 75 , wherein the imidazoquinoline compound is imiquimod and the retinoid agent is tazarotene. 
     
     
         83 . The method of  claim 75 , wherein the condition is selected from a wart,  molluscum contagiosum,  a keloid, and a skin cancer. 
     
     
         84 . The method of  claim 75 , wherein the condition is a wart. 
     
     
         85 . The method of  claim 75 , wherein the condition is  Molluscum contagiosum.    
     
     
         86 . The method of  claim 75 , wherein the condition is a keloid scar or a hypertrophic scar. 
     
     
         87 . The method of  claim 75 , wherein the condition is a skin cancer. 
     
     
         88 . The method of  claim 87 , wherein the skin cancer is selected from melanoma and non-melanoma skin cancers, actinic keratoses, basal cell carcinomas, squamous cell carcinoma-in-situ or Bowen's disease, melanoma in-situ, and other unresectable carcinomas. 
     
     
         89 . The method of  claim 87 , wherein the skin cancer is actinic keratoses. 
     
     
         90 . The method of  claim 87 , wherein the skin cancer is selected from: cutaneous T-cell lymphoma, extramammary Paget's disease, lentigo maligna, cutaneous melanoma metastases, and cutaneous leishmaniasis. 
     
     
         91 . The method of  claim 75 , wherein the composition is administered to a mucosal surface of the subject. 
     
     
         92 . The method of  claim 75 , wherein the subject is receiving antirejection therapy following a transplant. 
     
     
         93 . The method of  claim 75 , wherein the retinoid agent is provided in the composition at a final concentration between about 1% (wt/wt) and about 0.001% (wt/wt). 
     
     
         94 . The method of  claim 75 , wherein the imidazoquinoline compound is provided in the composition at a final concentration between about 10% (wt/wt) and about 0.1% (wt/wt). 
     
     
         95 . The method of  claim 75 , wherein the composition is substantially stable at a temperature of 50° C. for a period of four (4) weeks.