METHODS AND COMPOSITIONS FOR SAFE AND EFFECTIVE TREATMENT OF ERYTHEMA

• US 20110286944A1
• Filed: 03/25/2011
• Published: 11/24/2011
• Est. Priority Date: 03/26/2010
• Status: Active Grant

• Current Assignee: Galderma Laboratories LP (Galderma Holding SA)
• Original Assignee: Galderma, S.A. (Galderma Holding SA)
• Inventors: LEONI, Matthew J., LOESCHE, Christian, LIU, Yin-Sang, FREIDENREICH, Philip, GRAEBER, Michael
• Granted Patent: US 8,513,247 B2
• Time in Patent Office: Days
• US Class Current: 424/59
• 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 providing a safe and effective treatment of 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 about 0.4% to about 0.6% by weight brimonidine and a pharmaceutically acceptable carrier, wherein the topical administration effects a serum or plasma profile of brimonidine having a mean C_max of about 54±

28 pg/mL or less and a mean AUC_0-24hr of about 568±

277 pg·

hr/mL or less.

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

3. The method of claim 1, further comprising administering 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 topical administration of the topical composition to the skin area results in significantly more reduction of the erythema or the symptom compared to a vehicle control as measured by a 12 hour success profile evaluated on both CEA and PSA scales, wherein the 12 hour success profile comprises a noticeable effect of 1-grade improvement of the erythema or the symptom and 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 a noticeable 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

about 0.20% (w/w) to about 4.0% (w/w) gelling agent;

and

about 5.0% (w/w) to about 15.0% (w/w) at least one polyol.

8. The method of claim 7, wherein the topical composition comprises about 0.4% to about 0.6% by weight of brimonidine tartrate.

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

10. The method of claim 7, wherein the topical composition comprises about 0.50% (w/w) to about 2.0% (w/w) carbomer.

11. The method of claim 10, wherein the carbomer is selected from the group consisting of carbomer 934P, Carbopol®

974P, and Carbopol®

980.

12. The method of claim 7, wherein the topical composition further comprises about 0.04% to about 0.08% (w/w) 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 topical composition comprises at least one of glycerin and propylene glycol.

15. A method of producing a packaged product for providing a safe and effective treatment of erythema or a symptom associated therewith in a subject, comprising:

(1) obtaining a topical composition comprising about 0.4% to about 0.6% by weight 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 safe and effective treatment, and

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

wherein the topical administration effects a serum or plasma profile of brimonidine having a mean C_max of about 54±

28 pg/mL or less and a mean AUC_0-24hr of about 568±

277 pg·

hr/mL or less.

16. A topical gel composition for providing a safe and effective treatment of erythema or a symptom associated therewith in a subject, comprising:

about 0.4% (w/w) to about 0.6% (w/w) brimonidine;

about 0.20% (w/w) to about 4.0% (w/w) gelling agent; and

about 5.0% (w/w) to about 15.0% (w/w) at least one polyol,

wherein the topical administration of the topical gel composition to a skin area affected by the erythema or the symptom effects a serum or plasma profile of brimonidine having a mean C_max of about 54±

28 pg/mL or less and a mean AUC_0-24hr of about 568±

277 pg·

hr/mL or less.

17. The topical gel composition of claim 16, comprising about 0.4% to about 0.6% by weight of brimonidine.

18. The topical gel composition of claim 16, comprising about 0.5% by weight of brimonidine tartrate.

19. The topical gel composition of claim 16, comprising about 0.50% (w/w) to about 2.0% (w/w) carbomer.

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