FORMULATIONS OF VITAMIN K ANALOGS FOR TOPICAL USE
The present invention provides topical formulations containing a vitamin K analog, e.g., menadione, that deliver a uniform, therapeutically effective concentration of the vitamin K analog to the skin in a vehicle which is stable, non-irritating, non-drying and cosmetically acceptable. These topical formulations are useful for the treatment and prevention of dermatological conditions associated with inflammation, particularly, dermatological conditions resulting from anti-EGFR therapies.
1 . A method of treating a dermatological condition comprising topically administering to a patient a pharmaceutical formulation comprising a vitamin K analog, a lipophylic component, a gelling agent, and water.
2 . The method of claim 1 , wherein the dermatological condition is skin rash, psoriasis, eczema, dermatitis, hair loss, or acne.
3 . The method of claim 1 , wherein the dermatological condition is secondary to an anti-epidermal growth factor receptor (EGFR) therapy.
4 . The method of claim 3 , wherein the anti-EGFR therapy is treatment with an anti-EGFR antibody.
5 . The method of claim 3 , wherein the anti-EGFR therapy is treatment with an EGFR tyrosine kinase inhibitor.
6 . The method of claim 1 , wherein the vitamin K analog activates EGFR.
7 . The method of claim 1 , wherein the vitamin K analog is menadione.
8 . The method of claim 1 , wherein the vitamin K analog comprises from about 0.01 to 10% (w/w) of the pharmaceutical formulation.
9 . The method of claim 1 , wherein the lipophilic component is selected from the group consisting of isopropyl myristate, caprylic/capric triglyceride, diethyl sebacate, diisopropyl adipate, petrolatum, mineral oil, and cyclomethicone.
10 . The method of claim 1 , wherein the lipophilic component comprises from about 1 to 100% (w/w) of the pharmaceutical formulation.
11 . The method of claim 1 , wherein the gelling agent comprises from about 0.1 to 5% (w/w) of the pharmaceutical formulation.
12 . The method of claim 1 , wherein water comprises from about 30 to 95% (w/w) of the pharmaceutical formulation.
13 . The method of claim 1 , wherein the pharmaceutical formulation further comprises a preservative.
14 . The method of claim 13 , wherein the preservative comprises from about 0.01 to 50% (w/w) of the pharmaceutical formulation.
15 . The method of claim 1 , wherein the pharmaceutical formulation further comprises a neutralizing agent.
16 . The method of claim 15 , wherein the neutralizing agent maintains the pH of the formulation at about 4.0 to 8.0.
17 . The method of claim 1 wherein the pharmaceutical formulation is a cream or a lotion.
18 . The method of claim 17 , wherein the lotion has a viscosity of approximately 1,000 to 20,000 cps.
19 . A method of treating a dermatological condition comprising administering to a patient a topical pharmaceutical formulation comprising, a) from about 0.01 to 10% (w/w) of menadione; b) from about 1 to 50% (w/w) of a lipophilic component; c) from about 0.01 to 5% (w/w) each of one or more acrylic acid based polymers; e) from about 0.03 to 10% (w/w) of a preservative; f) a neutralizing agent sufficient to maintain a pH of about 4.0 to 7.0; and g) water.
20 . The method of claim 19 , wherein the dermatological condition is skin rash, psoriasis, eczema, dermatitis, hair loss, or acne.