Compositions and methods for topical administration of pharmaceutically active agents

• US 5,332,576 A
• Filed: 05/21/1993
• Issued: 07/26/1994
• Est. Priority Date: 02/27/1991
• Status: Expired due to Term

• Current Assignee: Noven Pharmaceuticals Inc (Hisamitsu Pharmaceutical Company Incorporated)
• Original Assignee: Noven Pharmaceuticals Inc (Hisamitsu Pharmaceutical Company Incorporated)
• Inventors: Mantelle, Juan A.
• Primary Examiner(s): Michl, Paul R.
• Assistant Examiner(s): AZPURU, CARLOS A
• Application Number:
  US08/064,587
• Time in Patent Office: 431 Days
• Field of Search: 424/435, 424/443, 424/447, 424/449, 424/450, 424/484, 424/485, 424/486, 424/487, 424/488, 514/781, 514/782, 514/818, 514/947, 514/772.6
• US Class Current: 424/443
• 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 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/215 of carboxylic acids
• CPC Class Codes: A61K 31/245 Amino benzoic acid types, e.g. procaine, novocaine salicylic acid esters A61K31/60
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4453 only substituted in position 1, e.g. propipocaine, diperodon
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• 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

A composition for topical application comprising a therapeutically effective amount of a pharmaceutical agent(s), a flexible, finite, pharmaceutically acceptable, bioadhesive carrier, and a solvent for the pharmaceutical agent(s) in the carrier and a method of administering the pharmaceutical agent to a mammal are disclosed.

Claims

1. A method for administering one or more local anesthetic agents to a subject comprising the steps of:

(a) providing a composition comprising a therapeutically effective amount of at least one local anesthetic;

a pharmaceutically acceptable solvent for the anesthetic, in an amount from about 5 to about 70 weight percent based on the weight of the whole composition;

and in admixture with the anesthetic agent in the solvent, a flexible, finite, pharmaceutically acceptable polysaccharide bioadhesive carrier in an amount from about 20 to about 50 weight percent based on the weight of the whole composition;

wherein said composition is substantially free of water is substantially water insoluble and is a bioadhesive; and

(b) contacting an area of skin or mucous membrane with the composition to administer the local anesthetics.

2. The method of claim 1, wherein the anesthetic agent is selected from the group consisting of procaine, dyclonine, lidocaine, prilocaine, mepivacaine, benzocaine, propoxycaine, chloroprocaine, tetracaine, bupivacaine, etidocaine, and dibucaine.

3. The method of claim 1, wherein the anesthetic agent is administered in the form of a free base.

4. The method of claim 1, wherein the anesthetic agent is administered in the form of an acid-addition salt.

5. The method of claim 1, wherein the solvent is at least one polyhydric alcohol.

6. The method of claim 5, wherein the polyhydric alcohol is a polyalkylene glycol.

7. The method of claim 6, wherein the glycol is selected from the group consisting of dipropylene glycol, propylene glycol, polyethylene glycol, glycerin, butylene glycol, hexylene glycol, polypropylene glycol, sorbitol, and ethylene glycol.

8. A method of administering one or more local anesthetic agents to a subject comprising the steps of:

(a) providing a composition comprising a therapeutically effective amount of a first local anesthetic agent in base form;

a therapeutically effective amount of a different, second local anesthetic agent in an acid-addition salt form;

a pharmaceutically acceptable solvent for the anesthetic in an amount which ranges from about 5 to about 70 weight percent based on the weight of the whole composition; and

in admixture with the anesthetic agent in the solvent, a flexible, finite, pharmaceutically acceptable bioadhesive carrier in an amount from about 20 to about 50 weight percent based on the weight of the whole composition;

wherein said composition is substantially free of water and is substantially water insoluble; and

(b) contacting an area of skin or mucous membrane with the composition to administer the local anesthetics.

9. The method of claim 8, wherein the first local anesthetic agent in base form is selected from the group consisting of procaine, dyclonine, lidocaine, prilocaine, mepivacaine, benzocaine, propoxycaine and chloroprocaine and the second local anesthetic agent in acid-addition salt form is selected from the group consisting of a dyclonine salt, a prilocaine salt, a tetracaine salt, a bupivacaine salt, a mepivacaine salt, a lidocaine salt, a procaine salt, an etidocaine salt, and a dibucaine salt.

10. The method of claim 9, wherein the acid-addition salt is hydrochloride.

11. The method of claim 8, wherein the bioadhesive is selected from the group consisting of polyacrylates, polyacrylic acids, gums and celluloses.

12. The method of claim 11, wherein the gum is selected from the group consisting of karaya gum, tragacanth gum, pectin gum, xanthan gum and guar gum.

13. The method of claim 12, wherein the solvent for the anesthetic agents is at least one polyhydric alcohol.

14. The method of claim 13, wherein the polyhydric alcohol is a polyalkylene glycols.

15. The method of claim 14, wherein the glycol is selected from the group consisting of dipropylene glycol, propylene glycol, ethylene glycol, polyethylene glycol, and sorbitol.