Monoglyceride/lactate ester permeation enhancer for codelivery of steroids

• US 5,686,097 A
• Filed: 03/09/1995
• Issued: 11/11/1997
• Est. Priority Date: 09/29/1993
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Taskovich, Lina Tormen, Crisologo, Nieves Marzan, Yum, Su Il
• Primary Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US08/401,593
• Time in Patent Office: 978 Days
• Field of Search: 424/447, 424/448, 424/449, 514/946
• US Class Current: 424/448
• 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 31/215 of carboxylic acids
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• 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 9/7053 obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system

Abstract

A composition of matter for application to a body surface or membrane to coadminister an estrogen and progesterone by permeation through the body surface or membrane, the composition comprising, in combination, the estrogen and progesterone to be administered, in a therapeutically effective amount; and a permeation-enhancing mixture comprising a monoglyceride or a mixture of monoglycerides, and a lactate ester or a mixture of lactate esters at specific concentrations. The composition of matter is used to provide hormone replacement therapy to a woman.

Claims

1. A composition of matter for application to a body surface or membrane to coadminister an estrogen and progestogen by permeation through the body surface or membrane, the composition comprising, in combination:

(a) the estrogen and progestogen to be administered, in a therapeutically effective amount; and

(b) a permeation-enhancing mixture comprising;

(i) 20% by weight of a monoglyceride or a mixture of monoglycerides, and

(ii) 12% by weight of a lactate ester or a mixture of lactate esters.

2. A composition according to claim 1 wherein the lactate ester is lauryl lactate.

3. A composition according to claim 2, wherein the monoglyceride is glycerol monolaurate.

4. A composition according to claim 1 wherein the estrogen is estradiol.

5. A composition according to claim 4 wherein the estradiol comprises from about 0.6 to about 5% by weight of the composition.

6. A composition according to claim 4 or 5 wherein the progestogen is progesterone and comprises from about 10 to about 15% by weight of the composition.

7. A device for the transdermal coadministration, at a therapeutically effective rate, of an estrogen and progestogen, which device comprises:

(a) a reservoir comprising a therapeutically effective amount of an estrogen and progestogen and a skin permeation-enhancing amount of a permeation mixture comprising;

(i) 20% by weight of a monoglyceride or a mixture of monoglycerides, and

(ii) 12% by weight of a lactate ester or a mixture of lactate esters;

(b) a backing on the skin-distal surface of the reservoir; and

(c) means for maintaining the reservoir in drug- and permeation enhancing mixture-transmitting relation with the skin.

9. A device according to claim 7 or 8 wherein the monoglyceride is glycerol monolaurate.

10. A device according to claim 7 or 8 wherein the lactate ester is lauryl lactate.

11. A device according to claim 7 or 8 wherein the estrogen is estradiol.

12. A device according to claim 11 wherein the estradiol comprises about 0.6 to about 5% by weight of the drug containing reservoir.

13. A device according to claim 12 wherein the progestogen is progesterone and comprises about 10 to about 15% by weight of the drug containing reservoir.

14. A device according to claim 7 wherein the means for maintaining the reservoir in relation with the skin comprises an in-line adhesive layer on the skin-proximal surface of the reservoir.

17. A device according to claim 10, wherein the monoglyceride is glycerol monolaurate.

27. A device according to claim 13 wherein the monoglyceride is glycerol monolaurate and the lactate ester is lauryl lactate.

8. A device for the transdermal coadministration, at a therapeutically effective rate, of an estrogen and progestogen which device comprises:

(a) a first reservoir comprising a therapeutically effective amount of an estrogen and progestogen, and a skin permeation-enhancing amount of a permeation mixture comprising;

(i) 20% by weight of a monoglyceride or a mixture of monoglycerides, and

(ii) 12% by weight of a lactate ester or a mixture of lactate esters;

(b) a second reservoir comprising an excess of the permeation enhancing mixture and the estrogen and progestogen at or below saturation;

(c) a rate-controlling membrane between the first reservoir and the second reservoir;

(d) a backing on the skin-distal surface of the second reservoir; and

(e) means for maintaining the first and second reservoirs in drug- and permeation enhancing mixture-transmitting relation with the skin.

15. A device according to claim 8 wherein the means for maintaining the reservoirs in relation with the skin comprises an in-line adhesive layer on the skin-proximal surface of the first reservoir.

16. A device according to claim 8 wherein the first reservoir also is an adhesive layer which functions as the means for maintaining the reservoirs in relation with the skin.

18. A method for the transdermal coadministration of an estrogen and progestogen, which method comprises:

(a) administering the estrogen and progestogen at a therapeutically effective rate to an area of skin; and

(b) simultaneously administering a permeation enhancing mixture comprising;

(i) 20% by weight based on the drug and permeation enhancer mixture of a monoglyceride or a mixture of monoglycerides, and

(ii) 12% by weight based on the drug and permeation enhancer mixture of a lactate ester or a mixture of lactate esters, to the area of skin at a rate which is sufficient to substantially increase the permeability of the area to the drug.

19. A method according to claim 18, wherein the monoglyceride is glycerol monolaurate.

20. A method according to claim 18, wherein the lactate ester is lauryl lactate.

21. A method according to claim 18, wherein the estrogen is estradiol.

25. A method according to claim 18 wherein the monoglyceride is glycerol monolaurate and the lactate ester is lauryl lactate.

28. A method according to claim 18 wherein the progestogen is progesterone.

22. A method for providing hormone replacement therapy to a woman, the method comprising the steps of:

(a) administering each component of a drug formulation comprised of an estrogen and progestogen at a therapeutically effective rate to an area of the woman'"'"'s skin;

(b) simultaneously administering a skin permeation enhancing amount of a permeation enhancing mixture comprising;

(i) 20% by weight of a monoglyceride or a mixture of monoglycerides, and

(ii) 12% by weight of a lactate ester or a mixture of lactate esters.

23. A method according to claim 22 wherein the monoglyceride is glycerol monolaurate and wherein the lactate ester is lauryl lactate.

24. A method according to claim 22 or 23 wherein the estrogen is estradiol.

26. A method according to claim 22 wherein the monoglyceride is glycerol monolaurate and the lactate ester is lauryl lactate.

29. A method according to claim 22 wherein the progestogen is progesterone.

30. A method according to claim 22 wherein the monoglyceride is glycerol monolaurate.

31. A method according to claim 22 wherein the lactate ester is lauryl lactate.