Benzodiazepine compositions for treating epidermal hyperplasia and related disorders
View Patent ↗The present invention provides, for example, pharmaceutical compositions comprising a benzodiazepine compound and an agent selected from the group consisting of a topical steroid, a keratolytic agent, a topical retinoid, a coal tar, and a vitamin D-3 analog. The pharmaceutical compositions are useful for treating medical disorders, such as epidermal hyperplasia.
1. A method of regulating hyperproliferating epithelium cells in a subject, comprising administering an effective amount of a benzodiazepine compound of Formula I or II to the subject to regulate the hyperproliferating epithelium cells, wherein Formula I is represented by:
including pharmaceutically acceptable salts and both R and S enantiomeric forms and racemic mixtures thereof; wherein
R 1 is hydrogen or alkyl;
R 2 is halogen;
R 3 and R 4 each represent independently hydrogen or alkyl;
R 5 is one of the following:
and
n is 0-5; and
Formula II is represented by:
including pharmaceutically acceptable salts thereof; wherein
R 1 is one of the following: napthalalanine,
2. The method of claim 1 , wherein said method decreases Erk1/2 activation in said epithelium cells.
3. The method of claim 1 , wherein said method inhibits keratinocyte proliferation in said subject.
4. The method of claim 1 , further comprising administering a topical corticosteroid to the subject.
5. The method of claim 4 , wherein said topical corticosteroid is selected from the group consisting of triamcinolone acetonide 0.1% cream and betamethasone dipropionate 0.05% cream.
6. The method of claim 1 , further comprising administering coal tar 2-10% to the subject.
7. The method of claim 1 , further comprising administering a vitamin D-3 analog to the subject.
8. The method of claim 7 , wherein said vitamin D-3 analog is calcipotriene.
9. The method of claim 1 , further comprising administering a keratolytic agent to the subject.
10. The method of claim 9 , wherein said keratolytic agent is anthralin 0.1-1%.
11. The method of claim 1 , further comprising administering a topical retinoid to the subject.
12. The method of claim 11 , wherein said topical retinoid is selected from the group consisting of tretinoin and tazarotene.
13. The method of claim 1 , wherein said subject is a human being suffering from epidermal hyperplasia.
14. The method of claim 13 , wherein said subject has psoriasis.
15. The method of claim 1 , wherein said benzodiazepine compound is Bz-423.
16. The method of claim 1 , wherein the method decreases the proliferation of epithelium cells.
17. The method of claim 16 , wherein the benzodiazepine compound is a compound of Formula I.
18. The method of claim 17 , wherein R 1 is alkyl, and R 3 and R 4 are hydrogen.
19. The method of claim 18 , wherein R 5 is
20. The method of claim 19 , wherein the alkyl groups specified in the definition of variable R 5 are methyl groups.
21. A method of decreasing the proliferation of hyperproliferating epithelium cells in a subject, comprising administering an effective amount of a benzodiazepine compound of Formula I-A or II-A to the subject to decrease the proliferation of hyperproliferating epithelium cells, wherein Formula I-A is represented by:
including pharmaceutically acceptable salts and both R and S enantiomeric forms and racemic mixtures thereof; wherein
R 1 is hydrogen or alkyl;
R 2 is halogen;
R 3 and R 4 each represent independently hydrogen or alkyl;
R 5 is one of the following:
and
n is 0-5; and
Formula II-A is represented by:
including pharmaceutically acceptable salts thereof; wherein
R 1 is one of the following: napthalalanine,
22. A method of regulating hyperproliferating epithelium cells in a subject, comprising administering an effective amount of a benzodiazepine compound of Formula I-B to the subject to regulate the hyperproliferating epithelium cells, wherein Formula I-B is represented by:
including pharmaceutically acceptable salts and both R and S enantiomeric forms and racemic mixtures thereof; wherein
R 1 is alkyl;
R 2 is halogen;
R 3 and R 4 each represent independently hydrogen; and
R 5 is