TOPICAL EMULSION OF AN ANTICHOLINERGIC COMPOUND

Abstract

The present invention relates to a topical emulsion comprising at least one anticholinergic compound, an oil phase, a water phase and an emulsifier for use in treating patients suffering from hyperhidrosis rated as 1 or 2, preferably as 2, in the Hyperhidrosis Disease Severity Scale (HDSS). In addition the present invention relates to the non-therapeutic use of such a topical emulsion for reducing sweating in subjects who experience ordinary sweating and/or excessive sweating, wherein the subjects suffer from sweating rated as or 2, preferably as 2, in the Hyperhidrosis Disease Severity Scale (HDSS).

Claims

1. A topical emulsion comprising: at least one anticholinergic compound, an oil phase, a water phase, and an emulsifier, for use in treating patients suffering from hyperhidrosis rated as 1 or 2 in the Hyperhidrosis Disease Severity Scale (HDSS).

2. The topical emulsion according to claim 1 in the form of an oil-in-water emulsion comprising: a) a disperse/inner oil phase; b) a continuous/outer water phase containing the anticholinergic compound; and c) the emulsifier.

3. The topical emulsion according to claim 1, wherein the anticholinergic compound is selected from the group of glycopyrronium (GP) salts, umeclidinium salts, and sofpironium salts.

4. The topical emulsion according to claim 3, wherein the GP salt is a racemic mixture of (3R)-3-[(2S)-(2-cyclopentyl-2-hydroxy-2-phenylacetyl)oxy]-1,1-dimethylpyrrolidinium bromide and (3S)-3-[(2R)-(2-cyclopentyl-2-hydroxy-2-phenylacetyl)oxy]-1,1-dimethylpyrrolidinium bromide; or a racemic mixture of (3R)-3-[(2S)-(2-cyclopentyl-2-hydroxy-2-phenylacetyl)oxy]-1,1-dimethylpyrrolidinium tosylate and (3S)-3-[(2R)-(2-cyclopentyl-2-hydroxy-2-phenylacetyl)oxy]-1,1-dimethylpyrrolidinium tosylate.

5. The topical emulsion according to claim 3, wherein the GP salt is present in an amount of 0.05 to 5 wt. %, based on the weight of the total emulsion.

6. The topical emulsion according to claim 1, wherein the emulsifier is an emulsifier system comprising: at least one macrogol glycerol fatty acid ester, at least one glycerol fatty acid ester, and at least one fatty alcohol.

7. The topical emulsion according to claim 6 comprising as the emulsifier system a combination of: macrogol glycerol monostearate, glycerol monostearate, and a mixture of cetyl and stearyl alcohol.

8. The topical emulsion for use according to claim 6 comprising as the emulsifier system a combination of: macrogol 20 glycerol monostearate, glycerol monostearate 40-55, and cetostearyl alcohol.

9. The topical emulsion according to claim 6 comprising, an amount of 4.0 to 10.0 wt. % of the macrogol glycerol fatty acid ester, an amount of 1.5 to 7.5 wt. % of glycerol fatty acid ester, and an amount of 5.0 to 11.0 wt. % of fatty alcohol, based on the weight of the total emulsion, respectively.

10. The topical emulsion according to claim 6, wherein the emulsifier system comprises: an amount of 21 to 51 wt. % of macrogol glycerol fatty acid ester, an amount of 8 to 38 wt. % of glycerol fatty acid ester, and an amount of 26 to 56 wt. % of fatty alcohol, based on the weight of the emulsifier system.

11. The topical emulsion according to claim 1, wherein the hyperhidrosis to be treated is selected from the group consisting of primary and secondary hyperhidrosis, gustatory sweating associated with Frey's syndrome, gustatory sweating associated with diabetic autonomic neuropathy, and excessive sweating.

12. The topical emulsion according to claim 1, wherein the emulsion is topically applied onto the skin of a mammal 1-4 times a day.

13. The topical emulsion according to claim 12, wherein the emulsion is topically applied 1 time per day within an induction period of four weeks and subsequently 2-3 times per week.

14. A pharmaceutical composition comprising the topical emulsion according to claim 1 and one or more pharmaceutically acceptable excipients.

15. A non-therapeutic use of a topical emulsion comprising: at least one anticholinergic compound, an oil phase, a water phase, and an emulsifier, for reducing sweating in subjects who experience ordinary sweating and/or excessive sweating, wherein the subjects suffer from sweating rated as 1 or 2 in the Hyperhidrosis Disease Severity Scale (HDSS).

16. The topical emulsion according to claim 3, wherein the anticholinergic compound is selected from the group consisting of the bromide, the acetate, and the tosylate salts of glycopyrronium (GP), umeclidinium, and sofpironium, respectively.

17. The topical emulsion according to claim 5, wherein the GP salt is present in an amount of 0.5 to 1.5 wt. %, based on the weight of the total emulsion.

18. The topical emulsion according to claim 6 comprising: an amount of 6.5 to 7.5 wt. % of the macrogol glycerol fatty acid ester, an amount of 4.0 to 5.0 wt. % of glycerol fatty acid ester, and an amount of 7.5 to 8.5 wt. % of fatty alcohol, based on the weight of the total emulsion, respectively.

19. The topical emulsion according to claim 6, wherein the emulsifier system comprises: an amount of 33 to 38 wt. % of macrogol glycerol fatty acid ester, an amount of 21 to 26 wt. % of glycerol fatty acid ester, and an amount of 38 to 44 wt. % of fatty alcohol, based on the weight of the emulsifier system

20. The topical emulsion according to claim 1, wherein the emulsion is topically applied onto the skin of a mammal 2-3 times per week.

Description

[0039] FIG. 1 shows the Percentage Sweat Reduction from baseline to Day 2-Day 21; pooled Placebo vs. pooled GPB, Cohort 1-3 (only patients starting with a HDSS of 2).

[0040] FIG. 2 shows the Percentage of Patients with 1-point improvement in HDSS from baseline to Day 2-Day 21, pooled Placebo vs. pooled GPB, Cohort 1-3 (only patients starting with a HDSS of 2).

[0041] The above Preparation Examples 1 to 3 containing 0.5 to 2.0 wt. % GPB were assessed for their efficacy in treating hyperhidrosis in patients suffering from hyperhidrosis rated as 2 in the Hyperhidrosis Disease Severity Scale (HDSS). They were topically applied once daily for 14 days on the skin of patients suffering from hyperhidrosis.

[0042] Results of Preparation Examples 1 to 3 are as follows: The sweat production after one application was reduced up to 75%, and reduction of sweat production after 13 days of treatment on day 14 was up to >90% (FIG. 1). In the four point HDSS (hyperhidrosis disease severity scale) a one-point improvement was observed for 40% of patients after one application and for 60% of patients on day 14 following 13 days of treatment (FIG. 2).

[0043] The above-mentioned results clearly show that the topical emulsion according to the present invention is highly effective in the treatment of hyperhidrosis even in patients suffering from hyperhidrosis rated as only 1 or 2, in particular as 2, in the HDSS. Thus, the topical emulsion according to the present invention is highly effective in the treatment of even mild or moderate hyperhidrosis.

[0044] Apart from the efficacy the emulsion of the present invention showed local excellent tolerability and mainly a local effect. In addition, the cosmetic acceptance of the O/W emulsion was high. The emulsion provides improved skin care characteristics including smoothening and moisturizing effects.