# US 2014/0178459 A1 · Compositions and methods for transdermal delivery of hormones and other medicinal agents

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- Number: US 2014/0178459 A1
- Document ID: US20140178459A1
- Status: Published application
- Kind: A1
- Application number: 14/135,770
- Filed: 2013-12-20
- Published: 2014-06-26
- Earliest claimed: 2012-12-21
- Assignees: Teikoku Pharma USA, Inc.
- Applicants: Teikoku Pharma USA, Inc.
- Inventors: Edward Kisak; Nadir Buyuktimkin; Servet Buyuktimkin; John Newsam; Jianye Wen; Jutaro Shudo; Amit Jain
- Web page: https://patentgrep.com/patent/US20140178459A1

## CPC

- A61K 9/7061: {Polyacrylates}
- A61K 31/565: not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K 31/567: substituted in position 17 alpha, e.g. mestranol, norethandrolone
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- A61P 15/18: Feminine contraceptives
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention provides transdermal delivery systems, medical kits, and methods for using the transdermal delivery systems and kits for medical applications, such as delivery of contraceptive agents to control fertility.

## Claims

### Claim 1

A transdermal delivery system, comprising a backing layer affixed to an adhesive polymer matrix, wherein the adhesive polymer matrix comprises:
a. about 0.5% (w/w) to about 10% (w/w) of a first penetration enhancer selected from the group consisting of levulinic acid and a pharmaceutically acceptable salt thereof;
b. about 0.5% (w/w) to about 10% (w/w) of a second penetration enhancer selected from the group consisting of glyceryl monooleate and lauryl lactate;
c. an adhesive polymer;
d. a humectant;
e. levonorgestrel; and
f. ethinyl estradiol.

### Claim 2 (depends on 1)

The transdermal delivery system of claim 1, wherein the first penetration enhancer is levulinic acid.

### Claim 3 (depends on 1)

The transdermal delivery system of claim 1, wherein the second penetration enhancer is glyceryl monooleate.

### Claim 4 (depends on 1)

The transdermal delivery system of claim 1, wherein the second penetration enhancer is lauryl lactate.

### Claim 5 (depends on 1)

The transdermal delivery system of claim 1, wherein the adhesive polymer matrix comprises from about 3% (w/w) to about 5% (w/w) of the first penetration enhancer.

### Claim 6 (depends on 1)

The transdermal delivery system of claim 1, wherein the adhesive polymer matrix comprises from about 3.5% (w/w) to about 4.0% (w/w) of the first penetration enhancer.

### Claim 7 (depends on 1)

The transdermal delivery system of claim 1, wherein the adhesive polymer matrix comprises from about 2.0% (w/w) to about 3.0% (w/w) of the second penetration enhancer.

### Claim 8 (depends on 1)

The transdermal delivery system of claim 1, wherein the adhesive polymer matrix comprises from about 2.25% (w/w) to about 2.75% (w/w) of the second penetration enhancer.

### Claim 9 (depends on 1)

The transdermal delivery system of claim 1, wherein the adhesive polymer matrix comprises from about 7.0% (w/w) to about 8.0% (w/w) of the second penetration enhancer.

### Claim 10 (depends on 1)

The transdermal delivery system of claim 1, wherein the ratio of weight percent of first penetration enhancer to second penetration enhancer in the adhesive polymer matrix is in the range of about 1:1 to 2:1.

### Claim 11

(canceled)

### Claim 12

(canceled)

### Claim 13

(canceled)

### Claim 14

(canceled)

### Claim 15 (depends on 1)

The transdermal delivery system of claim 1, wherein the adhesive polymer is a polyacrylate copolymer.

### Claim 16 (depends on 1)

The transdermal delivery system of claim 1, wherein the adhesive polymer is a polyacrylate copolymer comprising a 2-ethylhexyl acrylate monomer.

### Claim 17

(canceled)

### Claim 18 (depends on 1)

The transdermal delivery system of claim 1, wherein the adhesive polymer is a random copolymer of 2-ethylhexyl acrylate and vinyl acetate.

### Claim 19

(canceled)

### Claim 20 (depends on 1)

The transdermal delivery system of claim 1, wherein the adhesive polymer matrix comprises from about 80% (w/w) to about 92% (w/w) adhesive polymer.

### Claim 21 (depends on 1)

The transdermal delivery system of claim 1, wherein the adhesive polymer matrix comprises from about 88% (w/w) to about 90% (w/w) adhesive polymer.

### Claim 22 (depends on 1)

The transdermal delivery system of claim 1, wherein the humectant comprises a polyvinylpyrrolidone copolymer.

### Claim 23 (depends on 1)

The transdermal delivery system of claim 1, wherein the humectant comprises a copolymer of vinylpyrrolidone and vinyl acetate.

### Claim 24 (depends on 1)

The transdermal delivery system of claim 1, wherein the humectant is a copolymer of vinylpyrrolidone and vinyl acetate, said copolymer having a weight average molecular weight of about 30,000 g/mol to about 50,000 g/mol.

### Claim 25 (depends on 1)

The transdermal delivery system of claim 1, wherein the humectant is a copolymer of vinylpyrrolidone and vinyl acetate, said copolymer having a weight average molecular weight of about 40,000 g/mol.

### Claim 26 (depends on 25)

The transdermal delivery system of claim 25, wherein the copolymer of vinylpyrrolidone and vinyl acetate comprises (i) from about 55% (w/w) to about 65% (w/w) vinylpyrrolidone and (ii) from about 35% (w/w) to about 45% (w/w) vinyl acetate.

### Claim 27

(canceled)

### Claim 28 (depends on 1)

The transdermal delivery system of claim 1, wherein the adhesive polymer matrix comprises from about 2.75% (w/w) to about 3.75% (w/w) humectant.

### Claim 29 (depends on 1)

The transdermal delivery system of claim 1, wherein the adhesive polymer matrix comprises from about 0.6% (w/w) to about 1.0% (w/w) levonorgestrel.

### Claim 30 (depends on 1)

The transdermal delivery system of claim 1, wherein the adhesive polymer matrix comprises from about 0.6% (w/w) to about 1.0% (w/w) ethinyl estradiol.

### Claim 31

A transdermal delivery system, comprising a backing layer affixed to an adhesive polymer matrix, wherein the adhesive polymer matrix comprises:
a. about 3.5% (w/w) to about 4% (w/w) of a first penetration enhancer selected from the group consisting of levulinic acid and a pharmaceutically acceptable salt thereof;
b. about 2.2% (w/w) to about 2.8% (w/w) of a second penetration enhancer that is glyceryl monooleate;
c. about 86% (w/w) to about 90% (w/w) of an adhesive polymer that is a random copolymer of 2-ethylhexyl acrylate and vinyl acetate;
d. about 2% (w/w) to about 4% (w/w) of a humectant that is a copolymer of vinylpyrrolidone and vinyl acetate;
e. about 0.7% (w/w) to about 0.9% (w/w) levonorgestrel; and
f. about 0.7% (w/w) to about 0.9% (w/w) ethinyl estradiol.

### Claim 32

(canceled)

### Claim 33

A transdermal delivery system, comprising a backing layer affixed to an adhesive polymer matrix, wherein the adhesive polymer matrix comprises:
a. about 3.5% (w/w) to about 4% (w/w) levulinic acid;
b. about 6% (w/w) to about 9% (w/w) lauryl lactate;
c. about 80% (w/w) to about 88% (w/w) of an adhesive polymer that is an acrylate-vinylacetate copolymer;
d. about 2% (w/w) to about 4% (w/w) of a humectant that is a copolymer of vinylpyrrolidone and vinyl acetate;
e. about 0.7% (w/w) to about 0.9% (w/w) levonorgestrel; and
f. about 0.7% (w/w) to about 0.9% (w/w) ethinyl estradiol.

### Claim 34

(canceled)

### Claim 35

(canceled)

### Claim 36 (depends on 1)

The transdermal delivery system of claim 1, formulated for delivery of ethinyl estradiol and levonorgestrel, wherein the ethinyl estradiol is transdermally delivered at a rate of from about 5 μg to about 25 μg per day for a term of about seven days, and the levonorgestrel is transdermally delivered at a rate of about 25 μg to about 35 μg per day for a term of about seven days.

### Claim 37 (depends on 1)

The transdermal delivery system of claim 1, formulated for delivery of ethinyl estradiol and levonorgestrel, wherein the ethinyl estradiol is transdermally delivered at a rate of from about 10 μg to about 20 μg per day for a term of about seven days, and the levonorgestrel is transdermally delivered at a rate of about 30 μg per day for a term of about seven days.

### Claim 38 (depends on 1)

The transdermal delivery system of claim 1, wherein the levonorgestrel is transdermally delivered in an amount sufficient to produce a serum concentration of at least 1,000 pg/mL in a human.

### Claim 39 (depends on 1)

The transdermal delivery system of claim 1, wherein the adhesive polymer matrix has a thickness of about 50 μm to about 150 μm.

### Claim 40 (depends on 1)

The transdermal delivery system of claim 1, wherein the adhesive polymer matrix has a thickness of about 100 μm.

### Claim at position 41

41-47. (canceled)

### Claim 48 (depends on 1)

A method of transdermally administering levonorgestrel and ethinyl estradiol to a subject, comprising applying a transdermal delivery system of claim 1 to the skin of the subject.

### Claim 49 (depends on 1)

A method of controlling fertility in a female subject, comprising applying a transdermal delivery system of claim 1 to the skin of the female subject.

### Claim 50 (depends on 49)

The method of claim 49, wherein the transdermal delivery system is replaced once each week for at least three successive weeks.