Estradiol penetration enhancers

• US 6,090,404 A
• Filed: 10/11/1996
• Issued: 07/18/2000
• Est. Priority Date: 01/13/1994
• Status: Expired due to Fees

• Current Assignee: LTS Lohmann Therapie-Systeme GmbH
• Original Assignee: LTS Lohmann Therapie-Systeme GmbH
• Inventors: Seibertz, Frank, Meconi, Reinhold
• Primary Examiner(s): Dees, Jose' G.
• Assistant Examiner(s): Shelborne, Kathryne E.
• Application Number:
  US08/682,511
• Time in Patent Office: 1,376 Days
• Field of Search: 42/448, 42/449, 604/896, 604/897
• 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 31/565 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 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 9/7069 obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide

Abstract

An active substance-containing patch for the controlled release of estradiol or its pharmaceutically acceptable derivatives alone or in combination with gestagens from a backing layer, an active substance-containing reservoir connected thereto and produced by using pressure sensitive adhesives and at least one penetration enhancer, and a removable protective layer is characterized by the fact that the penetration enhancer is selected from substances based on carboxylic acids.

Claims

1. An active substance-containing patch for the controlled release of estradiol or a pharmaceutically acceptable derivative thereof, alone or in combination with a gestagen, said patch comprising (1) a backing layer, (2) an active substance-containing reservoir connected thereto and which is produced using pressure sensitive adhesives and at least one penetration enhancer, and (3) a removable protective layer, wherein the penetration enhancer is based on polyfunctional carboxylic acids, and is selected from the group consisting of glycollic acid, mandelic acid, 2-hydroxy-cinnamic acid, 3-hydro xycinnamic acid, trans-4-methoxycinnamic acid, 2-hydroxyoctanoic acid, tropic acid, gallic acid, shikimic acid, benzylic acid, benzene-1,2,4-tricarboxylic acid, dimethyl-3-oxoglutarate, 3-methyl-2-oxo-valerianic acid, 4-methyl-2-oxo-valerianic acid, 2-oxoglutaric acid, pyruvic acid, 4-aminobutyric acid, 6-amino-hexanoic acid, 11-aminoundecanoic acid, asparaginic acid, 2-aminobenzoic acid, 3-aminobenzoic acid, 4-aminobenzoic acid, 4-amino-2-salicylic acid, 3-phenylpropionic acid, 2-phenylbutyric acid, 4-phenylbutyric acid, trans-2-dodecanedioic acid, tridecanedioic acid, tetradecanedioic acid, pentadecanedioic acid, diglycollic acid, piperidine-4-carboxylic acid, pyrazine-2-carboxylic acid, pyrazine-2,3-dicarboxylic acid, pyridine-2-carboxylic acid, nicotinic acid, pimelic acid monomethyl ester, malonic acid diamide, adipic acid diamide, pyrazine-2-carboxamide and succinic acid diamide.

2. The active substance patch according to claim 1, wherein the reservoir comprises the penetration enhancer in a concentration of 0.01-20%-wt.

3. The active substance patch according to claim 1, wherein the pressure sensitive adhesive comprises polymers in a concentration of at least 6%-wt.

4. The active substance patch according to claim 1, wherein the pressure sensitive adhesive comprises tackifying resins in the concentration of 5-94%-wt.

5. The active substance patch according to claim 1, wherein the reservoir comprises the active substance in concentration totaling 2-15%-wt.

6. The active substance patch according to claim 1, wherein the administration is in combination with a gestagen and the molar ratio of estradiol or a pharmaceutically acceptable derivative thereof to gestagen is 1:

1 to 1;

10.

7. The active substance patch according to claim 1, wherein the reservoir comprises up to 5%-wt. of inactive ingredients of the group consisting of dyes, fillers, antiageing agents and plasticizers with antioxidants.

8. The active substance patch according to claim 1, wherein the reservoir is formed of several layers.

9. The active substance patch according to claim 1, wherein the thickness of the reservoir is in the range of 0.02-1.0 mm.

10. The active substance patch according to claim 1, wherein the reservoir is provided with an additional pressure sensitive adhesive layer or with a pressure sensitive adhesive edge.

11. A method for the administration of estradiol or a pharmaceutically acceptable derivative thereof to a human or an animal in need of such treatment which comprises applying to the skin of such human or animal an active substance-containing patch as defined in claim 1.