Bioadhesive compositions and methods of treatment therewith

• US 5,225,196 A
• Filed: 01/07/1991
• Issued: 07/06/1993
• Est. Priority Date: 11/14/1983
• Status: Expired due to Fees

• Current Assignee: Columbia Laboratories, Inc. (Catalent, Inc.)
• Original Assignee: Columbia Laboratories, Inc. (Catalent, Inc.)
• Inventors: Robinson, Joseph R.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): HORNE, LEON
• Application Number:
  US07/638,184
• Time in Patent Office: 911 Days
• Field of Search: 424/427, 424/428, 424/434, 514/177
• US Class Current: 424/427
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• 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 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006

Abstract

A controlled release treatment composition method of use are disclosed. The composition includes a bioadhesive and an effective amount of a treating agent. The bioadhesive is a water-swellable, but water-insoluble, fibrous, cross-linked carboxy-functional polymer containing (a) a plurality of repeating units of which at least about 80 percent contain at least one carboxyl functionality, and (b) about 0.05 to about 1.5 percent cross-linking agent substantially free from polyalkenyl polyether.

Claims

1. A controlled release ophthalmic treatment composition comprising a bioadhesive and an effective amount of an ophthalmic treating agent, said bioadhesive comprising a water-swellable, but water-insoluble, particulate cross-linked carboxyl-functional polymer said polymer derived from monomers selected from the group consisting of acrylic acid, methacrylic acid, fumaric acid, maleic acid, maleic anhydride, itaconic acid, crotonic acid and mixtures thereof having particles sized so that visual impairment is substantially minimized when said composition is contacted with a mucous membrane of the eye, said polymer containing (a) a plurality of repeating units of which at least about 80 percent contain at least one carboxyl functionality, and (b) a cross-linked agent substantially free from polyalkenyl polyether said agent selected from the group consisting of divinyl benzend, N,N-dialkylacrylamide, 3,4-dihydroxy-1,5-hexadiene and 2,5-dimethyl-1,5-hexadiene, said agent being from about 0.05 to 2.0 weight.

2. A controlled release ophthalmic treatment composition as recited in claim 1 wherein said bioadhesive and said treating agent are intimately admixed substantially uniform.

3. A controlled release ophthalmic treatment composition as recited in claim 1 wherein at least about 90 percent of said polymer repeating units contain at least one carboxyl functionality.

4. A controlled release ophthalmic treatment composition as recited in claim 1 wherein at least about 95 percent of said polymer repeating units contain at least one carboxyl funtionality.

5. A controlled release ophthalmic treatment composition as recited in claim 1 wherein said polymer contains about 0.01 to about 2 percent by weight of polymerized cross-linking agent.

6. A controlled release ophthalmic treatment composition as recited in claim 1 wherein said carboxyl functionality is provided by polymerized acrylic acid.

7. A controlled release ophthalmic treatment composition as recited in claim 1 wherein at least about 95 percent of said polymer repeating units contain at least one carboxyl functionality provided by acrylic acid, and said polymer contains about 0.01 to about 2 percent by weight of polymerized cross-linking agent.

8. A controlled release ophthalmic treatment composition as recited in claim 7 wherein said cross-linking agent is 3,4-dihydroxy-1,5-hexadiene.

9. A controlled release ophthalmic treatment composition as recited in claim 7 wherein said cross-linking agent is divinyl benzene.

10. A controlled release ophthalmic treatment composition as recited in claim 7 wherein said cross-linking agent is 1,5-dimethyl-1,5-hexadiene.

11. A controlled release ophthalmic treatment composition as recited in any one of claims 1-10, inclusive, wherein said ophthalmic treating agent constitutes an anti-inflammatory agent.

12. A controlled release ophthalmic treatment composition as recited in claim 11 wherein said anti-inflammatory agent is fluorometholone.

13. A method of controlled release ophthalmic treatment comprising the steps of:

(A) providing a controlled release ophthalmic treatment composition comprising a bioadhesive and an effective amount of ophthalmic treating agent, said bioadhesive comprising a water-swellable, but water-insoluble , particulate cross-linked carboxyl-functional polymer derived from monomers selected from the group consisting of acrylic acid, methacrylic acid, fumaric acid, maleic acid, maleic anhydride, itaconic acid, crotonic acid, and mixtures thereof having particles sized so that visual impairment is minimized when said composition is contacted with a mucous membrane of the eye, said polymer containing (a) a plurality of repeating units of which at least about 80 percent contain at least one carboxyl functionality, and (b) a cross-linking agent substantially free from polyalkenyl polyether said agent selected from the group consisting of divinyl benzene, N,N-dialkylacrylamide, 3,4-dihydroxy-1,5-hexadiene and 2,5-dimethyl-1,5-hexadiene, said agent being from about 0.05 to 2.0 weight percent.

14. A method as recited in claim 13 wherein said bioadhesive and said treating agent are intimately admixed substantially uniformly.

15. A method as recited in claim 13 wherein at least about 90 percent of said polymer repeating units contain at least one carboxyl functionality.

16. A method as recited in claim 13 wherein said polymer contains about 0.01 to about 2 percent by weight of polymerized cross-linking agent.

17. A method as recited in claim 13 wherein said carboxyl functionality is provided by polymerized acrylic acid.

18. A method as recited in claim 13 wherein said anti-inflammatory agent is fluorometholone.

19. A method as recited in claim 18 wherein said anti-inflammatory agent is fluorometholone.