Combination therapy for treatment of skin diseases

Abstract

Described herein are pharmaceutical compositions comprising one or more modulators of a cytochrome 450 enzyme (CYP450) and substituted or unsubstituted diindolylmethane. Also described herein are methods for treating one or more skin conditions by administering a combination therapy comprising substituted or unsubstituted diindolylmethane and one or more modulators of CYP450. In particular, methods are disclosed for improving bioavailability and pharmacokinetic parameters of substituted or unsubstituted diindolylmethane following the combination therapy.

1 . A pharmaceutical composition comprising a first component comprising a modulator of a CYP450 enzyme and a second component comprising a substituted or unsubstituted diindolylmethane, wherein said composition is for treating a skin condition, wherein the modulator of the CYP450 enzyme comprises quercetin, wherein the first and second components are in separate dosage forms, and wherein the second component is formulated for sublingual administration. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the first component comprises about 100 mg to about 1000 mg of the modulator. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the second component comprises about 15 mg to about 100 mg of the substituted or unsubstituted diindolylmethane. 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . The pharmaceutical composition of  claim 1 , wherein the first component comprises about 100 mg to about 1000 mg of the quercetin. 
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein the first component comprises about 400 mg to about 600 mg of the quercetin. 
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein the first component comprises about 400 mg to about 500 mg of the quercetin. 
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the second component comprises about 45 mg to about 55 mg or about 85 mg to about 100 mg of the substituted or unsubstituted diindolylmethane. 
     
     
         16 . The pharmaceutical composition of  claim 15 , wherein the second component comprises about 30 mg to about 100 mg of the substituted or unsubstituted diindolylmethane. 
     
     
         17 . The pharmaceutical composition of  claim 16 , wherein the second component comprises about 45 mg of the substituted or unsubstituted diindolylmethane. 
     
     
         18 . The pharmaceutical composition of  claim 17 , further comprising a third component comprising a substituted or unsubstituted retinoic acid based compound. 
     
     
         19 . The pharmaceutical combination of  claim 18 , wherein the third component comprises about 100 μg to about 1000 μg of the substituted or unsubstituted retinoic acid based compound. 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . The pharmaceutical composition of  claim 1 , wherein the daily dosage of the second component further comprises about 200 μg to about 3000 μg of a vitamin A compound. 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . (canceled) 
     
     
         38 . (canceled) 
     
     
         39 . (canceled) 
     
     
         40 . The pharmaceutical composition of  claim 1 , wherein percentage of the substituted or unsubstituted diindolylmethane metabolized by the CYP450 enzyme is reduced by about 0.1% to about 10% compared to a control composition that does not comprise the first component. 
     
     
         41 . The pharmaceutical composition of  claim 9 , wherein the metabolism of the substituted or unsubstituted diindolylmethane by the CYP1A2 is reduced by about 0.1% to about 10% compared to a control composition that does not comprise the quercetin. 
     
     
         42 . The pharmaceutical composition of  claim 9 , wherein bioavailability of the substituted or unsubstituted diindolylmethane is increased by about 1-fold to about 100-folds compared to a control composition that does not comprise the quercetin. 
     
     
         43 . The pharmaceutical composition of  claim 1 , wherein the first component is formulated for administering via an oral route. 
     
     
         44 . (canceled) 
     
     
         45 . (canceled) 
     
     
         46 . (canceled) 
     
     
         47 . The pharmaceutical composition of  claim 9 , wherein a ratio between the quercetin and the substituted or unsubstituted diindolylmethane (quercetin:DIM in mg:mg) is between about 15:1 and 10:1. 
     
     
         48 . The pharmaceutical composition of  claim 9 , wherein a ratio between the quercetin and the substituted or unsubstituted diindolylmethane (quercetin:DIM in mg:mg) is about 11:1. 
     
     
         49 . (canceled) 
     
     
         50 . The pharmaceutical composition of  claim 49 , wherein the vitamin A compound comprises retinyl palmitate. 
     
     
         51 . (canceled) 
     
     
         52 . The pharmaceutical composition of  claim 1 , wherein the second component further comprises about 400 retinol equivalents of a vitamin A compound. 
     
     
         53 . (canceled)