Bioadhesive compositions and methods of treatment therewith

• US 4,615,697 A
• Filed: 12/20/1984
• Issued: 10/07/1986
• Est. Priority Date: 11/14/1983
• Status: Expired due to Term

• Current Assignee: Columbia Laboratories, Inc. (Catalent, Inc.)
• Original Assignee: Bio-Mimetics, Inc.
• Inventors: Robinson, Joseph R.
• Primary Examiner(s): Kight, John
• Assistant Examiner(s): Draper, Garnette D.
• Application Number:
  US06/690,483
• Time in Patent Office: 656 Days
• Field of Search: 424/19, 424/22, 424/21, 604/890, 604/894, 604/897
• US Class Current: 424/428
• 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 9/7061 Polyacrylates
• CPC Class Codes: Y10T 428/28 Web or sheet containing structurally defined element or component and having an adhesive outermost layer
• CPC Class Codes: Y10T 428/2848 Three or more layers

Abstract

A controlled release treatment composition and 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 treatment composition including a bioadhesive and an effective amount of a treating agent, said bioadhesive comprising a water-swellable, but water-insoluble, fibrous, cross-linked carboxy-functional polymer, said 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, said percentages being based upon the weights of unpolymerized repeating unit and cross-linking agent, respectively.

2. The controlled release composition according to claim 1 wherein said bioadhesive and said treating agent are intimately admixed substantially uniformly.

3. The controlled release composition according to claim 2 wherein said bioadhesive is in the form of comminuted particles capable of passing through the screen of a sieve having a 100 mesh size, U.S. Standard Sieve Series, and said treating agent is present as a saturated solute in a physiologically acceptable aqueous carrier.

4. The controlled release compositon according to claim 1 wherein said treating agent is contained in a medicinally inert matrix in the form of a three-dimensional structure having at least one surface portion, and said bioadhesive is disposed on at least said one surface portion.

5. The controlled release composition according to claim 4 wherein said three-dimensional structure is capsular in form, and has a largest dimension of about 1 nanometer to about 5000 microns.

6. The controlled release composition according to claim 5 wherein a plurality of said capsules are adhered together by said bioadhesive and are in the form of a capsule aggregate.

7. The controlled release composition according to claim 4 wherein said three-dimensional structure is a film.

8. The controlled release composition according to claim 4 wherein said three-dimensional structure is a laminate defining at least one surface portion on which said bioadhesive is disposed and containing a plurality of medicinally inert matrices in layers, each of said layers defining a first surface and a second surface, and said layer surfaces being in stacked relation with adjacent surfaces being adhered together, at least one of said layers containing said treating agent in a first medicinally inert matrix, and a surface of one of said layers defining said at least one laminate surface portion on which said bioadhesive is disposed.

9. The controlled release composition according to claim 8 wherein said laminate has (a) said first medicinally inert matrix containing said treating agent as a first layer that defines at least one surface and (b) a second layer defining a first surface and a second surface, and comprising a second medicinally inert matrix, the second surface of said second layer adhered to said at least one surface of said first layer, the first surface of said second layer defining said at least one surface of said laminate on which said bioadhesive is disposed.

10. The controlled release composition according to claim 8 wherein said laminate has (a) said first medicinally inert matrix containing said treating agent as a first layer that defines a first surface and a second surface, (b) a second layer defining a first surface and a second surface, and comprising a second medicinally inert matrix, the second surface of said second layer adhered to said first surface of said first layer, the first surface of said second layer defining said at least one surface portion of said laminate on which said bioadhesive is disposed, and (c) a third layer defining a first surface and a second surface, and comprising a third medicinally inert matrix, the first surface of said third layer adhered to said second surface of said first layer.

11. The controlled release composition according to claim 10 wherein the second surface of said third layer defines a second surface portion of said three-dimensional structure.

12. The controlled release composition according to claim 11 wherein said bioadhesive is additionally disposed on said second surface portion of said three-dimensional structure.

13. The controlled release composition according to claim 10 wherein said first, second and third matrices are different materials.

14. The controlled release composition according to claim 8 wherein said treating agent is within capsules having a largest dimension of about 1 nanometer to about 5000 microns and said capsules are contained in said first medicinally inert matrix.

15. The controlled release composition according to claim 14 wherein said laminate has (a) said first medicinally inert matrix containing said treating agent within said capsules as a first layer that defines at least one surface, and (b) a second layer defining a first surface and a second surface, and comprising a second medicinally inert matrix, the second surface of said second layer adhered to said at least one surface of said first layer, the first surface of said second layer defining said at least one surface portion of said three-dimensional structure on which said bioadhesive is disposed.

16. The controlled release composition according to claim 15 wherein said first matrix and said second matrix are different materials.

17. The controlled release composition according to claim 14 wherein said laminate has (a) said first medicinally inert matrix containing said treating agent within said capsules as a first layer that defines a first surface and a second surface, (b) a second layer defining a first surface and a second surface, and comprising a second medicinally inert matrix, the second surface of said second layer adhered to said first surface of said first layer, the first surface of said second layer defining said at least one surface portion of said three-dimensional structure on which said bioadhesive is disposed, and (c) a third layer defining a first surface and a second surface, and comprising a third medicinally inert matrix, the first surface of said third layer adhered to said second surface of said first layer.

18. The controlled release composition according to claim 1 wherein said treating agent constitutes a sun screen.

19. The controlled release composition according to claim 1 wherein said treating agent constitutes an agent for treating cardiovascular conditions.

20. The controlled release composition according to claim 1 wherein said treating agent constitutes an agent for treating internal conditions.

21. The controlled release composition according to claim 1 wherein said treating agent constitutes an anti-inflammatory agent.

22. The controlled release composition according to claim 1 wherein said treating agent constitutes an anti-bacterial agent.

23. The controlled release composition according to claim 1 wherein at least about 90 percent of said polymer repeating units contain at least one carboxyl functionality.

24. The controlled release composition according to claim 1 wherein at least about 95 percent of said polymer repeating units contain at least one carboxyl functionality.

25. The controlled release composition according to claim 1 wherein said polymer contains about 0.1 to about 1 percent by weight of polymerized cross-linking agent.

26. The controlled release composition according to claim 1 wherein said carboxyl functionality is provided by polymerized acrylic acid.

27. The controlled release composition according to claim 1 wherein the ratio by weight of said bioadhesive to said treating agent being about 200,000:

1 to about 1;

100.

28. A method of controlled release treatment comprising the steps of:

(a) providing a controlled release treating composition including a bioadhesive and an effective amount of a treating agent, said bioadhesive comprising a water-swellable, but water-insoluble, fibrous, cross-linked carboxy-functional polymer, said 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, said percentages being based upon the weights of the unpolymerized repeating unit and cross-linking agent, respectively; and

(b) contacting an area of skin or mucus membrane to be treated with said composition, said contact being carried out in the presence of sufficient water to swell said bioadhesive.

29. The method according to claim 28 wherein said composition comprises an intimate mixture of said bioadhesive and said treating agent.

30. The method according to claim 28 wherein said bioadhesive is in the form of comminuted particles capable of passing through the screen of a sieve having a 100 mesh size, U.S. Standard Sieve Series, and said treating agent is present as a saturated salute in a physiologically acceptable aqueous carrier.

31. The method according to claim 30 wherein said composition is contacted with a mucus membrane of the eye.

32. The method according to claim 28 wherein said treating agent is contained in a first medicinally inert matrix in the form of a three-dimensional structure having at least one surface portion, and said bioadhesive is disposed on at least said one surface portion.

33. The method according to claim 32 wherein said structure further includes a second medicinally inert matrix as a layer adhered to said first medicinally inert matrix and defining said at least one surface portion on which said bioadhesive is disposed.

34. The method according to claim 28 wherein said composition is contacted with a mucus membrane of the gastro-intestinal tract.

35. The method according to claim 28 wherein said treating agent constitutes an agent for treating cardiovascular conditions.

36. A laminate defining at least one surface portion on which a bioadhesive is disposed and containing medicinally inert matrices in layers, each of said layers defining a first surface and a second surface, said layer surfaces being in stacked relation with surfaces of adjacent layers being adhered together, at least one of said medicinally inert matrix layers containing an effective amount of a treating agent, and a surface of one of said layers defining said at least one surface portion on which a bioadhesive is disposed, said bioadhesive comprising a water- swellable, but water-insoluble, fibrous, cross-linked carboxy-functional polymer, said 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, said percentages being based upon the weights of unpolymerized repeating unit and cross-linking agent, respectively.

37. The laminate according to claim 36 comprising three layers, said three layers being (a) a first medicinally inert matrix containing said treating agent as a first layer that defines a first surface and a second surface, (b) a second layer comprising a second medicinally inert matrix, the first surface of said second layer being adhered to the first surface of said first layer, and the second face of said second layer defining said at least one surface of said laminate on which said bioadhesive is disposed, and (c) a third layer comprising a third medicinally inert matrix, the first surface of said third layer being adhered to the second surface of said first layer.

38. The laminate according to claim 37 wherein said second surface of said third layer additionally defines a second surface portion of said laminate.

39. The laminate according to claim 38 containing additional bioadhesive disposed on said second surface portion of said laminate.