Transdermal therapeutic composition

• US 5,362,497 A
• Filed: 01/13/1992
• Issued: 11/08/1994
• Est. Priority Date: 05/25/1989
• Status: Expired due to Fees

• Current Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Original Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Inventors: Nonomura, Muneo, Yamada, Masayuki, Nishikawa, Kohei
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Azpuru, Carlos
• Application Number:
  US07/820,020
• Time in Patent Office: 1,030 Days
• Field of Search: 424/443, 424/445, 424/447, 424/449, 424/484, 424/485, 424/487, 424/488, 514/777, 514/781, 514/944, 514/946, 514/953, 514/964
• US Class Current: 424/449
• 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 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• 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 9/7061 Polyacrylates

Abstract

When a transdermal therapeutic composition which contains a pharmaceutically effective ingredient, a water-soluble absorption enhancer, a fat-soluble absorption enhancer and a super water-absorbent resin is applied to the skin of mammals, release of the pharmaceutically effective ingredient and the absorption enhancers is controlled and the pharmacological action lasts for a long period of time.

Claims

1. A transdermal therapeutic composition which comprises:

(i) 0.1 to 20% of a pharmaceutically effective ingredient;

(ii) 1 to 50% (w/w) water-soluble substance which enhances transdermal absorption of the pharmaceutically effective ingredient;

(iii) 0.1 to 80% (w/w) fat-soluble substance which enhances transdermal absorption of the pharmaceutically effective ingredient; and

(iv) 0.1 to 10% (w/w) vinyl acetate-acrylic acid ester copolymer hydrolyzate capable of absorbing about 50 to 2000 times its own weight of water, whereby upon contact with said water swells to form a hydrogel.

2. A transdermal therapeutic composition according to claim 1, wherein the transdermal absorption-enhancing water-soluble substance is an alkanediol containing 2 to 5 carbon atoms or an alkanetriol containing 2 to 5 carbon atoms.

3. A transdermal therapeutic composition according to claim 1, wherein the transdermal absorption-enhancing water-soluble substance is propylene glycol or 1,3-butanediol.

4. A transdermal therapeutic composition according to claim 1, wherein the transdermal absorption-enhancing fat-soluble substance is an aliphatic carboxylic acid containing 6 to 20 carbon atoms, an ester of an aliphatic carboxylic acid containing 6 to 20 carbon atoms with an alcohol containing 1 to 5 carbon atoms, or an aliphatic alcohol containing 6 to 20 carbon atoms.

5. A transdermal therapeutic composition according to claim 1, wherein the transdermal absorption-enhancing fat-soluble substance is an ester of an aliphatic monocarboxylic acid with an alcohol containing 1 to 5 carbon atoms.

6. A transdermal therapeutic composition according to claim 1, wherein the pharmaceutically effective ingredient is an angiotensin converting enzyme inhibitor, an adrenaline β

-receptor blocker, an adrenaline α

₂ -receptor agonist, a calcium antagonist, a coronary vasodilator, a cardiotonic glycoside, a peripheral vasodilator, a cerebral vasoactive agent, a neurotropic drug, a drug for autonomic nerve system, a anti-vertigo drug, an antipyretic, an analgesic, a bronchodilator, a digestive canal antispasmodic, an antarthritic, a vitamin, a polypeptide hormone, an androgen, an estrogen, an adrenal cortical steroid, or an anti-tumor drug.

7. A transdermal therapeutic composition according to claim 1, wherein the pharmaceutically effective ingredient is an angiotensin converting enzyme inhibitor.

8. A transdermal therapeutic composition according to claim 1, wherein the pharmaceutically effective ingredient is (R)-3-[(S)-1-carboxy-5-(4-piperidyl)pentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid.

9. A transdermal therapeutic composition according to claim 1, which is in the form of patch, cataplasma, hard ointment or tape.

10. A transdermal therapeutic composition according to claim 1, which contains (i) (R)-3-[(S)-1-carboxy-5-(4piperidyl)pentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid, (ii) propylene glycol, (iii) isopropyl myristate, (iv) a vinyl acetate-acrylic acid ester copolymer hydrolyzate, (v) an inorganic base and water.

11. A transdermal therapeutic composition according to claim 10, wherein the inorganic base is sodium hydroxide.

12. A transdermal therapeutic composition according to claim 1, further comprising a nonionic surfactant present at 0.5 to 20% (w/w).

13. A transdermal therapuetic composition according to claim 1, which is in a form of tape.