Water-soluble pressure-sensitive mucoadhesive and devices provided therewith for emplacement in a mucosa-lined body cavity

• US 5,700,478 A
• Filed: 08/03/1995
• Issued: 12/23/1997
• Est. Priority Date: 08/19/1993
• Status: Expired due to Term

• Current Assignee: Ortho-McNeil Pharmaceutical Incorporated (Johnson & Johnson)
• Original Assignee: Cygnus, Inc. (Johnson & Johnson)
• Inventors: Biegajski, James E., Scott, Ann M., Venkatraman, Subbu S.
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US08/505,185
• Time in Patent Office: 873 Days
• Field of Search: 424/430, 424/434, 424/435, 424/436, 424/437, 424/443, 514/772.3, 514/777, 514/778, 514/786, 514/781, 514/782
• US Class Current: 424/434
• CPC Class Codes: A61F 13/023 wound covering film layers without a fluid retention layer
• CPC Class Codes: A61F 13/0253 characterized by the adhesive material
• CPC Class Codes: A61F 2013/00642 soluble, e.g. in water
• CPC Class Codes: A61F 2013/00685 soluble in liquid, e.g. of particular pH
• CPC Class Codes: A61F 2013/0071 containing active agent
• CPC Class Codes: A61F 2013/00714 adhesives for mucosae
• CPC Class Codes: A61F 2013/00906 for transcutaneous or transdermal drugs application
• CPC Class Codes: A61F 2013/0091 with disinfecting or anaesthetics means, e.g. anti-mycrobic
• CPC Class Codes: A61F 2013/00914 with deodorising or perfuming means
• CPC Class Codes: A61F 6/06 for use by females A61F6/20 takes precedence
• CPC Class Codes: A61K 6/35 Preparations for stabilising dentures in the mouth
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: C08K 5/10 Esters; Ether-esters
• CPC Class Codes: C08L 1/284 with hydroxylated hydrocarbon radicals
• CPC Class Codes: C08L 1/286 substituted with acid radicals, e.g. carboxymethyl cellulose [CMC] C08L1/282 takes precedence
• CPC Class Codes: C08L 2666/28 Non-macromolecular organic substances
• CPC Class Codes: C08L 2666/34 Oxygen-containing compounds, including ammonium and metal salts
• CPC Class Codes: C08L 29/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: C08L 33/08 Homopolymers or copolymers of acrylic acid esters
• CPC Class Codes: C08L 39/06 Homopolymers or copolymers of N-vinyl-pyrrolidones
• CPC Class Codes: C08L 71/02 : Polyalkylene oxides
• CPC Class Codes: C09J 139/06 : Homopolymers or copolymers of N-vinyl-pyrrolidones
• CPC Class Codes: C09J 201/00 : Adhesives based on unspecified macromolecular compounds
• CPC Class Codes: C09J 2301/302 : the adhesive being pressure-sensitive, i.e. tacky at temperatures inferior to 30°C

Abstract

Water-soluble pressure-sensitive adhesives include a water-soluble polymer that is made tacky at room temperature by addition of a water-soluble plasticizer that is miscible with the polymer. Suitable polymers are solid at room temperature; and have a hydrophilicity as measured by water uptake greater than about 25%; they are liquid at room temperature and have a boiling point higher than about 80° C. The adhesives according to the invention may conveniently be provided in dry film form. Preferred water-soluble pressure-sensitive adhesives of the invention adhere both to mucosal surfaces and to a variety of materials that may constitute a part of a device or prosthesis to be held in a body cavity that has a mucosal lining. Also, a laminated device for the controlled release of a substance within a mucosa-lined body cavity includes the substance dissolved or dispersed in either or both of a water-soluble pressure-sensitive adhesive layer and optionally one or more water-soluble polymer layers. Also, devices for administering a substance over an extended time for relief of sore throat or cough, or for administering a breath freshening agent, particularly a mint odorant, include a water soluble polymer film layer containing the active ingredient, and a water soluble pressure sensitive mucoadhesive layer.

Claims

1. A water-soluble pressure-sensitive adhesive comprising a water-soluble polymer and a water-soluble plasticizer, said polymer having a T(g) or a T(m) greater than about 25°

C. and having a hydrophilicity greater than about 25%, said plasticizer being miscible with said polymer at room temperature and being liquid at room temperature and having a boiling point higher than 80°

C.

2. The water-soluble pressure sensitive adhesive of claim 1 wherein said polymer has a T(g) or a T(m) greater than about 30°

C.

3. The water-soluble pressure-sensitive adhesive of claim 1, said polymer comprising poly(vinyl pyrrolidone) and said plasticizer comprising glycerol.

4. The water-soluble pressure-sensitive adhesive of claim 3, said polymer further comprising hydroxy propyl cellulose.

5. The water-soluble pressure-sensitive adhesive of claim 3, comprising 95-40 weight % poly(vinyl pyrrolidone), 0-50 weight % hydroxy propyl cellulose, and 11-60 weight % glycerol.

6. The water-soluble pressure-sensitive adhesive of claim 5, said glycerol being present in the range 30-50 weight %.

7. The water-soluble pressure-sensitive adhesive of claim 1, in film form.

8. A dental prosthesis adhesive, comprising the water-soluble pressure-sensitive adhesive film of claim 7, shaped to conform to a portion of the mucosal surface-contacting surface of the dental prosthesis.

9. A laminated device for the controlled release of a substance within a mucosa-lined body cavity, said device comprising:

the water-soluble adhesive layer comprised of the water-soluble adhesive of claim 1; and

a water-soluble polymer layer;

wherein the substance is dissolved or dispersed in either or both of said adhesive or polymer layers.

10. The device of claim 9 wherein the device provides delayed-onset delivery of the substance.

11. The device of claim 10 wherein the polymer layer is substantially impermeable to the substance and does not contain the substance.

12. The laminated device of claim 11, said polymer layer being insoluble in water that is below 40°

C.

13. The laminated device of claim 12, said polymer layer comprising hydroxypropyl cellulose and sorbitan monostearate.

14. The device of claim 13 wherein the substance is a breath reodorant.

15. The device of claim 9 comprising one or more polymer layers and two or more substances to be delivered.

16. The device of claim 15 wherein the substances are delivered sequentially.

17. A laminated device for the controlled release of a substance within a mucosa-lined body cavity, said device comprising:

a water-soluble adhesive layer comprised of the water-soluble pressure-sensitive adhesive of claim 1;

a first water-soluble polymer layer; and

a second water-soluble polymer layer;

wherein the substance is dissolved or dispersed in any or all of said adhesive or polymer layers.

18. The device of claim 17 wherein the adhesive layer and the second polymer layer contain the substance and wherein the first polymer layer is disposed between the adhesive layer and the second polymer layer, and wherein the device provides for pulsatile delivery of the substance.

19. The device of claim 18 wherein the pulsatile delivery includes periods of no delivery of the substance.

20. The device of claim 17 further comprising a third polymer layer wherein the first and the third polymer layers contain the substance and wherein the first polymer layer is disposed between the adhesive layer and the second polymer layer and the second polymer layer is disposed between the first polymer layer and the third polymer layer and wherein the device provides for pulsatile delivery of the substance.

21. The device of claim 20 wherein the pulsatile delivery includes periods of no delivery of the substance.

22. A laminated device for the controlled release of a substance within a mucosa-lined body cavity comprising the substance dissolved or dispersed in a water-soluble pressure-sensitive adhesive layer comprising the water-soluble adhesive of claim 1.

23. A laminated composite device for delivering a substance into the oral cavity for relief of sore throat or cough, comprising a water soluble polymer film layer containing the active ingredient, and the water soluble pressure sensitive mucoadhesive layer of claim 1.

24. The laminated composite of claim 23 wherein the active ingredient is a medicament for the relief of sore throat pain.

25. The laminated composite of claim 24 wherein the active ingredient is selected from the group consisting of benzocaine, lidocaine and dyclonine.

26. The laminated composite of claim 23 wherein the active ingredient is a medicament for the relief of cough.

27. The laminated composite of claim 26 wherein the active ingredient is selected from the group consisting of dextromethorphan HBR, nospine, codeine phosphate, menthol.

28. The laminated composite of claim 24 additionally comprising a medicament for the relief of cough.

29. The laminated composite of claim 23 wherein the active-containing water soluble layer comprises a hydrophobic material that will not dissolve in water below 40°

C. and is hot water dispersible.

30. The laminated composite of claim 29 wherein the active-containing water soluble layer is selected from the group of materials consisting of monoglycerides, triglycerides, waxes, fatty acids, fatty alcohols and mixtures thereof.

31. The laminated composite of claim 23 wherein the polymer is selected from the group consisting of poly(vinyl pyrrolidone), poly(vinyl alcohol), hydroxy propyl cellulose, poly(ethylene oxide), poly(acrylic acid), polyacrylates, starch and starch derivatives, polysaccharides, sodium carboxymethyl cellulose, xanthan gum, karaya gum, and gelatin or mixtures thereof.

32. The laminated composite of claim 23 wherein the plasticizer is selected from the group consisting of glycerin, sorbitol, glycol, polysorbate 80, triethyl citrate, acetyl triethyl citrate and tributyl citrate.

33. The laminated composite of claim 23 further including a third polymer layer interposed between the adhesive layer and the active-containing layer.

34. A method for administering a substance over an extended time period for relief of sore throat or cough, comprising dissolving or dispersing the substance in a laminated water soluble device having the water soluble pressure sensitive adhesive layer of claim 1, and affixing the device onto a mucosal surface of the oral cavity.

35. The method of claim 34 wherein the substance is a medicament for the relief of sore throat pain.

36. The method of claim 35 wherein the medicament is selected from the group consisting of benzocaine, lidocaine and dyclonine.

37. The method of claim 34 wherein the substance is a medicament for the relief of cough.

38. The method of claim 37 wherein the medicament is selected from the group consisting of dextromethorphan HBR, noscpine, codeine phosphate.

39. The method of claim 38 additionally comprising a medicament for the relief of cough.

40. A method for administering a substance over an extended time period for relief of sore throat or cough, comprising dissolving or dispersing the substance in a laminated water soluble device having the water soluble pressure sensitive adhesive layer of claim 1, and affixing the device onto a mucosal surface of the oral cavity.

41. The device of claim 40, being a device for delivery of a substance to the subject.

42. The delivery device of claim 41, said device being constructed to deliver a substance into the body cavity in which the device is emplaced.

43. The delivery device of claim 41, said device being constructed to deliver a substance across a mucosal surface to which the basal pressure-sensitive adhesive surface of the device is affixed.

44. The device of claim 40, being a laminated device structure, wherein the water-soluble pressure sensitive portion comprises a basal layer of the device.

45. A laminated device for administering a mint aroma into the oral cavity over an extended time, said device including a basal layer comprising the water soluble pressure sensitive mucoadhesive polymer composition of claim 1, and an upper layer comprising a water soluble polymer composition and a mint flavoring.