Methods and compositions for safe and effective treatment of erythema

• US 8,513,247 B2
• Filed: 03/25/2011
• Issued: 08/20/2013
• Est. Priority Date: 03/26/2010
• Status: Active Grant

• Current Assignee: Galderma Laboratories LP (Galderma Holding SA)
• Original Assignee: Galderma Laboratories LP (Galderma Holding SA)
• Inventors: Graeber, Michael, Loesche, Christian, Freidenreich, Philip, Liu, Yin-Sang, Leoni, Matthew J.
• Primary Examiner(s): Liu, Sue
• Assistant Examiner(s): Chui, Helen
• Application Number:
  US13/072,096
• Publication Number:
  US 20110286944A1
• Time in Patent Office: 879 Days
• Field of Search: 514/249, 514/230.5, 514/401, 514/649, 514/651, 514/861
• US Class Current: 514/249
• CPC Class Codes: A61K 31/194 having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• CPC Class Codes: A61K 31/498 Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders

Abstract

Improved methods and compositions for safe and effective treatment of erythema or a symptom associated with erythema in a subject are described. The methods involve topically applying to an affected skin area a topical composition comprising about 0.4% to about 0.6% by weight of brimonidine and a pharmaceutically acceptable carrier.

Claims

1. A method of treating erythema or a symptom associated therewith in a subject, comprising topically administering to a skin area affected by the erythema or the symptom a topical composition comprising, relative to the total weight of the composition, 0.4% to 0.6% by weight of brimonidine and a pharmaceutically acceptable carrier, wherein the topical administration results in more reduction of the erythema or the symptom compared to a vehicle control as measured by a 12 hour success profile evaluated on both Clinician'"'"'s Erythema Assessment scores and Patient'"'"'s Self Assessment scales without causing unacceptable drug related adverse events, and the 12 hour success profile comprises at least 1-grade improvement of the erythema or the symptom.

2. The method of claim 1, wherein the erythema is erythema of rosacea.

3. The method of claim 1, further comprising providing to the subject at least one additional treatment and medication for erythema or the symptom associated therewith.

4. The method of claim 1, wherein the topical composition is administered to the skin area once daily.

5. The method of claim 1, wherein the 12 hour success profile further comprises about 1 hour to about 8 hours of 2-grade improvement of the erythema or the symptom.

6. The method of claim 5, wherein the erythema or the symptom is facial erythema associated with rosacea, and the 12 hour success profile comprises an effect of 1-grade improvement of the facial erythema and about 3 hours to about 6 hours of 2-grade improvement of the facial erythema.

7. The method of claim 1, wherein the topical composition further comprises, relative to the total weight of the composition,

about 0.20% to about 4.0% by weight of gelling agent;

and

about 5.0% to about 15.0% by weight of at least one polyol.

8. The method of claim 7, wherein the brimonidine is brimonidine tartrate.

9. The method of claim 8, wherein the topical composition comprises, relative to the total weight of the composition, about 0.5% by weight of brimonidine tartrate.

10. The method of claim 7, wherein the topical composition comprises, relative to the total weight of the composition, about 0.50% to about 2.0% by weight of of the gelling agent, and the gelling agent comprises a carbomer.

11. The method of claim 10, wherein the carbomer is selected from the group consisting of carbomer 934P, carbomer 974P, and carbomer 980.

12. The method of claim 7, wherein the topical composition further comprises, relative to the total weight of the composition, about 0.04% to about 0.08% by weight of water dispersible form of titanium dioxide.

13. The method of claim 7, wherein the topical composition further comprises a preservative selected from the group consisting of sodium benzoate, phenoxyethanol, benzyl alcohol, methylparaben, imidazolidinyl urea and diazolidinyl urea.

14. The method of claim 7, wherein the at least one polyol comprises at least one of glycerin and propylene glycol.

21. The method of claim 1, wherein the erythema or the symptom associated therewith is facial erythema associated with rosacea, and the topical composition comprises about 0.5% by weight of brimonidine tartrate relative to the total weight of the composition.

15. A method of producing a packaged product for treating erythema or a symptom associated therewith in a subject, comprising:

(1) obtaining a topical composition comprising, relative to the total weight of the composition, 0.4% to 0.6% by weight of brimonidine and a pharmaceutically acceptable carrier;

(2) devising instructions for topically administering the topical composition to a skin area affected by the erythema or the symptom to obtain the treatment, and

(3) providing the topical composition and the instructions in a unified package for the subject,

wherein the topical administration results in more reduction of the erythema or the symptom compared to a vehicle control as measured by a 12 hour success profile evaluated on both Clinician'"'"'s Erythema Assessment scores and Patient'"'"'s Self Assessment scales without causing unacceptable drug related adverse events, and the 12 hour success profile comprises at least 1-grade improvement of the erythema or the symptom.

16. A topical composition for treating erythema or a symptom associated therewith in a subject, comprising, relative to the total weight of the composition:

0.4% to 0.6% by weight of brimonidine;

and a pharmaceutically acceptable carrier,

wherein the topical administration of the topical gel composition to a skin area affected by the erythema or the symptom results in more reduction of the erythema or the symptom compared to a vehicle control as measured by a 12 hour success profile evaluated on both Clinician'"'"'s Erythema Assessment scores and Patient'"'"'s Self Assessment scales without causing unacceptable drug related adverse events, and the 12 hour success profile comprises at least 1-grade improvement of the erythema or the symptom.

17. The topical gel composition of claim 16, wherein the brimonidine is brimonidine tartrate.

18. The topical gel composition of claim 17 comprising, relative to the total weight of the composition, about 0.5% by weight of brimonidine tartrate.

19. The topical gel composition of claim 16, further comprising, relative to the total weight of the composition, about 0.50% to about 2.0% by weight of a carbomer.

20. The topical gel composition of claim 16, further comprising at least one of glycerin and propylene glycol.

22. The topical composition of claim 16, wherein the 12 hour success profile further comprises about 1 hour to about 8 hours of 2-grade improvement of the erythema or the symptom.

23. The topical composition of claim 22, wherein the erythema or the symptom is facial erythema associated with rosacea, and the 12 hour success profile comprises an effect of 1-grade improvement of the facial erythema and about 3 hours to about 6 hours of 2-grade improvement of the facial erythema.