Penetration enhancing and irritation reducing systems

• US 6,319,913 B1
• Filed: 11/09/1998
• Issued: 11/20/2001
• Est. Priority Date: 11/10/1997
• Status: Expired due to Term

• Current Assignee: Strakan International SA RL (Kirin Holdings Company Limited)
• Original Assignee: Cellegy Pharmaceuticals, Inc.
• Inventors: Mak, Vivien H. W., Grayson, Stephen
• Primary Examiner(s): Jarvis, William R. A.
• Assistant Examiner(s): KIM, VICKIE Y
• Application Number:
  US09/189,090
• Time in Patent Office: 1,107 Days
• Field of Search: 514/784, 514/947, 514/946, 424/448, 424/449
• US Class Current: 514/179
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/047 having two or more hydroxy groups, e.g. sorbitol
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/568 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• 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

Abstract

This invention lies in the technology of transdermal and topical drug delivery. In particular, the present invention relates to enhancement of the penetration of transdermally or topically applied drugs and with the reduction of skin irritation that often accompanies transdermal and topical drug delivery.

Claims

1. A method for administering a topically or systemically active agent with increased penetration, said method comprising:

topically administering to a mammal a composition comprising;

a) an active agent having a concentration of about 0.1% to about 2%, wherein said active agent is a member selected from the group consisting of testosterone, estradiol, derivatives thereof and the mixture thereof;

b) a penetration-enhancing system consisting essentially of (i) a membrane fluidizer comprising oleic acid;

(ii) a C₁-C₄ alcohol; and

(iii) a glycol said composition having a pH value of between about 4 to about 8, thereby administering a topically or systemically active agent with increased penetration.

2. A method in accordance with claim 1, wherein said penetration-enhancing system further comprises (iv) a gelling agent.

3. A method in accordance with claim 1, wherein said active agent is testosterone.

4. A method in accordance with claim 1, wherein said active agent is testosterone propionate.

9. A method in accordance with claim 1, wherein said pH value is between about 4.5 to about 6.5.

10. A method in accordance with claim 1, wherein said active agent is present in a concentration selected from the group consisting of 0.5%, 1.00%, 1.25%, 1.50% and 2.00% weight to weight of said composition.

11. A method in accordance with claim 1, wherein said C₁-C₄ alcohol is isopropanol.

12. A method in accordance with claim 1, wherein said glycol is propylene glycol.

13. A method in accordance with claim 1, wherein said gelling agent is Carbopol 1342.

14. A method in accordance with claim 1, wherein said penetration enhancing system fmal urther comprises an irritation reducing agent.

15. A method in accordance with claim 1, wherein said active agent is a mixture of testosterone and estradiol.

5. A method for reducing inflammation associated with topical application of a topically or systemically active agent, said method comprising:

topically administering to a mammal a composition comprising;

a) an active agent having a concentration of about 0.1% to about 2%, wherein said active agent is a member selected from the group consisting of testosterone, estradiol, derivatives thereof and the mixture thereof;

b) a penetration-enhancing system consisting essentially;

(i) a membrane fluidizer comprising oleic acid;

(ii) a C₁-C₄ alcohol; and

(iii) a glycol said composition having a pH value of between about 4 to about 8, thereby reducing inflammation associated with a topical application of a topically or systemically active agent.

6. A method in accordance with claim 5, wherein said penetration-enhancing system further comprises (iv) a gelling agent.

7. A method in accordance with claim 6, wherein said active agent is a member selected from the group consisting of testosterone, testosterone propionate and mixtures thereof.

8. A method in accordance with claim 7, wherein said active agent is testosterone propionate.

16. A method in accordance with claim 5, wherein said active agent is testosterone.

17. A method in accordance with claim 5, wherein said active agent is a mixture of testosterone and estradiol.

18. A method in accordance with claim 5, wherein said penetration enhancing system further comprises an iritation reducing agent.

19. A method for administering a topically or systemically active agent with increased penetration, said method comprising:

topically administering to a mammal a composition comprising;

a) testosterone or a derivative thereof having a concentration of about 0.1% to about 2%;

b) a penetration-enhancing system comprising;

(i) oleic acid;

(ii) a C₃ alcohol; and

(iii) propylene glycol thereby administering a topically or systemically active agent with increased penetration.

20. A method in accordance with claim 19, wherein testosterone or a derivative thereof is present in a concentration selected from the group consisting of 0.5%, 1.00%, 1.25%, 1.50% and 2.00% weight to weight of said composition.

21. A method in accordance with claim 19, wherein said penetration-enhancing system further comprises (iv) a gelling agent.

22. A method for administering a topically or systemically active agent with increased penetration, said method comprising:

topically administering to a mammal a composition comprising;

a) estradiol or a derivative thereof having a concentration of about 0.1% to about 10%;

b) a penetration-enhancing system comprising;

(i) oleic acid;

(ii) a C₃ alcohol; and

(iii) propylene glycol, thereby administering a topically or systemically active agent with increased penetration.

23. A method in accordance with claim 22, wherein estradiol or a derivative thereof is present from about 0.1% to about 5% weight to weight of said composition.

24. A method in accordance with claim 22, wherein estradiol or a derivative thereof is present from about 1% to about 2% weight to weight of said composition.

25. A method in accordance with claim 22, wherein estradiol or a derivative thereof is present in a concentration selected from the group consisting of 0.5%, 1.00%, 1.25%, 1.50% and 2.00% weight to weight of said composition.

26. A method in accordance with claim 22, wherein said penetration-enhancing system further comprises (iv) a gelling agent.