Formulations of vitamin K analogs for topical use
View Patent ↗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 topically applicable pharmaceutical formulation suitable for treatment of a dermatological condition comprising,
a) from about 0.01 to 2% (w/w) of menadione;
b) from about 1 to 50% (w/w) of a lipophilic component selected from the group consisting of isopropyl myristate, caprylic/capric triglyceride, diethyl sebacate, diisopropyl adipateand combinations thereof;
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;
wherein the formulation delivers a concentration of about 0.1 to 1.5 mM vitamin K3 to the epidermal skin layer when applied topically.
2. The pharmaceutical formulation of claim 1 comprising,
a) from about 0.05 to 2% (w/w) of menadione;
b) from about 3 to 20% (w/w) of the lipophilic component selected from the group consisting of isopropyl myristate, caprylic/capric triglyceride, diethyl sebacate, diisopropyl adipateand combinations thereof;
c) from about 0.1 to 1.0% (w/w) each of one or more acrylic acid based polymers;
e) from about 0.5 to 5% (w/w) of the preservative;
f) a neutralizing agent sufficient to maintain a pH of about 4.5 to 6.5; and
g) purified water;
wherein the formulation delivers a concentration of about 0.1 to 1.5 mM vitamin K3 to the epidermal skin layer when applied topically.
3. The pharmaceutical formulation of claim 1 , comprising
a) about 0.05 to 0.2% (w/w) menadione;
b) about 12% (w/w) isopropyl myristate;
c) about 0.3% (w/w) Acrylates/C10-30 Alkyl Acrylate Crosspolymer;
d) about 0.1% (w/w) prop-2-eonic acid carbomer;
e) about 1% (w/w) benzyl alcohol;
f) sodium hydroxide sufficient to maintain a pH of about 5.0 to 6.0; and
g) purified water.
4. The pharmaceutical formulation of claim 1 , comprising
a) about 0.05 to 0.2% (w/w) menadione;
b) about 3% (w/w) diethyl sebacate;
c) about 0.3% (w/w) Acrylates/C10-30 Alkyl Acrylate Crosspolymer;
d) about 0.1% (w/w) prop-2-eonic acid carbomer;
e) about 0.3% (w/w) each of methylparaben and propylparaben;
f) sodium hydroxide sufficient to maintain a pH of about 5.0 to 6.0; and
g) water.
5. The pharmaceutical formulation of claim 1 , comprising
a) about 0.05 to 0.2% (w/w) menadione;
b) about 6% (w/w) diisopropyl adipate;
c) about 0.3% (w/w) Acrylates/C10-30 Alkyl Acrylate Crosspolymer;
d) about 0.1% (w/w) prop-2-eonic acid carbomer;
e) about 0.3% (w/w) each of methylparaben and propylparaben;
f) sodium hydroxide sufficient to maintain a pH of about 5.0 to 6.0; and
g) water.
6. A packaged pharmaceutical formulation comprising the pharmaceutical formulation of -any one of claims 1 to 5 in a light impermeable container.
7. The pharmaceutical formulation of any one of claims 1 to 5 , wherein the formulation is ethyl alcohol free.
8. The pharmaceutical formulation of claim 1 , comprising about 0.05 to 2% (w/w) vitamin K3.
9. The pharmaceutical formulation of claim 1 or 2 , comprising about 0.01 to 0.5% (w/w) vitamin K3.
10. The pharmaceutical formulation of claims 1 or 2 , comprising about 0.01 to 0.2% vitamin K3.