Compositions and methods for treating rosacea and acne
Provided are compositions and methods for treating rosacea and acne. Specifically, a gel or foam composition having a tetracycline antibiotic and uses thereof for treating rosacea and acne are provided.
1. A method for treating acne vulgaris in a subject in need thereof, comprising topically administering to the subject a therapeutically effective amount of a breakable foam obtained from a foamable composition once daily for at least seven consecutive days, wherein the foamable composition comprises:
(a) a hydrophobic vehicle comprising:
(i) about 70% to about 90% by weight of the vehicle of a hydrophobic solvent comprising:
about 35% w/w to about 65% w/w of soybean oil;
about 16.5% w/w to about 30.7% w/w of coconut oil;
about 3.5% w/w to about 6.5% w/w of cyclomethicone; and
mineral oil; and
(ii) about 10% to about 22% by weight of the vehicle of a foamer complex comprising:
about 2.5% w/w to about 4.6% w/w of cetostearyl alcohol;
stearic acid;
about 1.8% w/w to about 3.3% w/w of myristyl alcohol;
about 1% w/w to about 3% w/w of hydrogenated castor oil;
about 1% w/w to about 3% w/w of beeswax;
stearyl alcohol; and
behenyl alcohol;
(iii) a minocycline or a salt thereof in an amount ranging from about 1% w/w to about 4% by weight of the vehicle; and
(b) a propellant in an amount ranging from about 3% to about 25% based on the weight of the total composition; and
wherein the subject is between 15 years old and 16 years and 11 months old;
wherein the foamable composition does not comprise silicon dioxide (SiO 2 ), and
wherein the foamable composition has antibacterial activity against one or more P. acnes strains; and
wherein the foamable composition has a low propensity to induce resistance in the one or more strains after topical administration.
2. The method of claim 1 , wherein the minocycline or salt thereof is in an amount of about 4% by weight of the vehicle.
3. The method of claim 1 , wherein the minocycline salt is minocycline hydrochloride.
4. The method of claim 1 , wherein the minocycline is present in plasma from the subject at a concentration of at most 1.9 ng/mL before applying the seventh day of treatment with the therapeutically effective amount of the breakable foam.
5. The method of claim 1 , wherein the minocycline is present in plasma from the subject at a concentration of about 1.8 ng/mL 3 hours after applying the seventh day of treatment with the therapeutically effective amount of the foam.
6. The method of claim 1 , wherein the minocycline is present in plasma from the subject at a concentration of about 1.8 ng/mL 12 hours after applying the seventh day of treatment with the therapeutically effective amount of the foam.
7. The method of claim 1 , wherein the minocycline is present in plasma from the subject at a concentration of about 1.6 ng/mL 16 hours after applying the seventh day of treatment with the therapeutically effective amount of the foam.
8. The method of claim 1 , wherein the minocycline is present in plasma from the subject at a concentration of about 1.5 ng/mL 24 hours after applying the seventh day of treatment with the therapeutically effective amount of the foam.
9. The method of claim 1 , wherein a maximum measured plasma concentration in the subject is reached about 6 hours after a daily topical administration.
10. The method of claim 1 , wherein the concentration of minocycline present in plasma from the subject at day 8 is about the same or less than the concentration before applying the seventh day of treatment.
11. A method of treating acne vulgaris in a subject in need thereof, comprising topically administering to the subject a therapeutically effective amount of a breakable foam obtained from a foamable composition once daily for at least seven consecutive days, wherein the foamable composition comprises:
(a) a hydrophobic vehicle comprising:
(i) about 70% to about 90% by weight of the vehicle of a hydrophobic solvent comprising:
about 35% w/w to about 65% w/w of soybean oil;
about 16.5% w/w to about 30.7% w/w of coconut oil;
about 3.5% w/w to about 6.5% w/w of cyclomethicone; and
mineral oil; and
(ii) about 10% to about 22% by weight of the vehicle of a foamer complex comprising:
about 2.5% w/w to about 4.6% w/w of cetostearyl alcohol;
stearic acid;
about 1.8% w/w to about 3.3% w/w of myristyl alcohol;
about 1% w/w to about 3% w/w of hydrogenated castor oil;
about 1% w/w to about 3% w/w of beeswax;
stearyl alcohol; and
behenyl alcohol;
(iii) minocycline or a salt thereof in an amount ranging from about 1% w/w to about 4% by weight of the vehicle; and
(b) a propellant in an amount ranging from about 3% to about 25% w/w based on the weight of the total composition;
wherein the subject is between 15 years old and 16 years and 11 months old,
wherein the minocycline is present in plasma from the subject, and wherein an area under a concentration-time curve of the amount of minocycline in the plasma from the subject is 40.8 (ng/mL)*hour or less, as determined during a 24 hour period following a topical administration of the therapeutically effective amount of the breakable foam,
wherein the foamable composition has antibacterial activity against one or more P. acnes strains, and
wherein the foamable composition has a low propensity to induce resistance in the one or more strains after topical administration.
12. The method of claim 11 , wherein the minocycline or salt thereof is in an amount of about 4% by weight of the vehicle.
13. The method of claim 11 , wherein the minocycline salt is minocycline hydrochloride.
14. A method of treating acne vulgaris in a subject in need thereof, comprising topically administering to the subject a therapeutically effective amount of a breakable foam obtained from a foamable composition once daily for at least seven consecutive days, wherein the foamable composition comprises:
(a) a hydrophobic vehicle comprising:
(i) about 70% to about 90% by weight of the vehicle of a hydrophobic solvent comprising:
about 35% w/w to about 65% w/w of soybean oil;
about 16.5% w/w to about 30.7% w/w of coconut oil;
about 3.5% w/w to about 6.5% w/w of cyclomethicone; and
mineral oil; and
(ii) about 10% to about 22% by weight of the vehicle of a foamer complex comprising:
about 2.5% w/w to about 4.6% w/w of cetostearyl alcohol;
stearic acid;
about 1.8% w/w to about 3.3% w/w of myristyl alcohol;
about 1% w/w to about 3% w/w of hydrogenated castor oil;
about 1% w/w to about 3% w/w of beeswax;
stearyl alcohol; and
behenyl alcohol;
(iii) minocycline or a salt thereof in an amount ranging from about 1% w/w to about 4% by weight of the vehicle; and
(b) a propellant in an amount ranging from about 3% to about 25% based on the weight of the total composition; and
wherein the foamable composition does not comprise silicon dioxide (SiO 2 ),
wherein seven days of topical treatment with the breakable foam at the therapeutically effective amount results in a maximum concentration of minocycline in plasma from the subject of about 2 ng/mL, as measured during a 24 hour period following the last topical administration, and
wherein the subject is between 15 years old and 16 years and 11 months old, and
wherein the foamable composition has antibacterial activity against one or more P. acnes strains, and
wherein the foamable composition has a low propensity to induce resistance in the one or more strains after topical administration.
15. The method of claim 14 , wherein the seven days of topical treatment with the therapeutically effective amount results in a concentration of minocycline in plasma from the subjects of about 1.4 ng/mL, as measured 24 hours after the last topical administration.
16. The method of claim 14 , wherein the area under a concentration-time curve of the amount of the minocycline in the plasma of the subjects is determined during a 24 hour period following the last topical administration.
17. The method of claim 14 , wherein the minocycline or salt thereof is in an amount of about 4% by weight of the vehicle.
18. The method of claim 14 , wherein the minocycline salt is minocycline hydrochloride.
19. A method of treating acne vulgaris in a subject in need thereof, comprising topically administering to the subject a therapeutically effective amount of a breakable foam obtained from a foamable composition once daily for at least seven consecutive days, wherein the foamable composition comprises:
(a) a hydrophobic vehicle comprising:
(i) about 70% to about 90% by weight of the vehicle of at least one hydrophobic solvent, wherein the hydrophobic solvent comprises soybean oil, coconut oil, cyclomethicone, and/or mineral oil; and
(ii) about 10% to about 22% by weight of the vehicle of a foamer complex comprising:
about 0.5% to about 16% of a fatty alcohol comprising cetostearyl alcohol, myristyl alcohol, stearyl alcohol, and behenyl alcohol;
about 0.8% to about 12% of a wax comprising hydrogenated castor oil and beeswax;
about 1% to about 10% of a fatty acid comprising stearic acid;
(iii) minocycline or a salt thereof in an amount ranging from about 1% w/w to about 4% by weight of the vehicle; and
(b) a propellant in an amount ranging from about 3% to about 25% based on the weight of the total composition; and
wherein the foamable composition does not comprise silicon dioxide (SiO 2 ),
wherein seven days of topical treatment with the breakable foam at the therapeutically effective amount results in a maximum concentration of minocycline in plasma from the subject of about 2 ng/mL, as measured during a 24 hour period following the last topical administration, and
wherein the subject is between 15 years old and 16 years and 11 months old, and
wherein the foamable composition has antibacterial activity against one or more P. acnes strains, and
wherein the foamable composition has a low propensity to induce resistance in the one or more strains after topical administration.
20. The method of claim 1 , wherein the mineral oil is in an amount of about 0.1% w/w to about 15% w/w, wherein the stearic acid is in an amount of about 0.5% w/w to about 5% w/w, wherein the stearyl alcohol is in an amount of about 0.5% w/w to about 7% w/w, and wherein the behenyl alcohol is in an amount of about 0.2% w/w to about 2% w/w.
21. The method of claim 1 , wherein the mineral oil is a light mineral oil which is in an amount of about 2% w/w to about 3.7% w/w, wherein the stearic acid is in an amount of about 2% w/w to about 4% w/w, wherein the stearyl alcohol is in an amount of about 1% w/w to about 2% w/w, and wherein the behenyl alcohol is in an amount of about 0.5% w/w to about 1.5% w/w.
22. The method of claim 11 , wherein the mineral oil is in an amount of about 0.1% w/w to about 15% w/w, wherein the stearic acid is in an amount of about 0.5% w/w to about 5% w/w, wherein the stearyl alcohol is in an amount of about 0.5% w/w to about 7% w/w, and wherein the behenyl alcohol is in an amount of about 0.2% w/w to about 2% w/w.
23. The method of claim 11 , wherein the mineral oil is a light mineral oil which is in an amount of about 2% w/w to about 3.7% w/w, wherein the stearic acid is in an amount of about 2% w/w to about 4% w/w, wherein the stearyl alcohol is in an amount of about 1% w/w to about 2% w/w, and wherein the behenyl alcohol is in an amount of about 0.5% w/w to about 1.5% w/w.
24. The method of claim 14 , wherein the mineral oil is in an amount of about 0.1% w/w to about 15% w/w, wherein the stearic acid is in an amount of about 0.5% w/w to about 5% w/w, wherein the stearyl alcohol is in an amount of about 0.5% w/w to about 7% w/w, and wherein the behenyl alcohol is in an amount of about 0.2% w/w to about 2% w/w.
25. The method of claim 14 , wherein the mineral oil is a light mineral oil which is in an amount of about 2% w/w to about 3.7% w/w, wherein the stearic acid is in an amount of about 2% w/w to about 4% w/w, wherein the stearyl alcohol is in an amount of about 1% w/w to about 2% w/w, and wherein the behenyl alcohol is in an amount of about 0.5% w/w to about 1.5% w/w.
26. The method of claim 19 , wherein the minocycline or salt thereof is in an amount of about 4% by weight of the vehicle.