Hydrogel Compositions

• US 20090258060A1
• Filed: 06/24/2009
• Published: 10/15/2009
• Est. Priority Date: 05/01/2001
• Status: Active Grant

• Current Assignee: Corium Pharma Solutions, Inc.
• Original Assignee: Anatoly E. Chalykh, Gary W. Cleary, Mikhail M. Feldstein, Nicolai A. Plate, Shoreh Parandoosh, Valery G. Kulichikhin
• Inventors: Parandoosh, Shoreh, Plate, Nicolai A., Cleary, Gary W., Feldstein, Mikhail M., Chalykh, Anatoly E., Kulichikhin, Valery G.
• Granted Patent: US 8,481,059 B2
• Time in Patent Office: Days
• US Class Current: 424/448
• CPC Class Codes: A61K 2800/262 Transparent; Translucent
• CPC Class Codes: A61K 2800/54 Polymers characterized by specific structures/properties
• CPC Class Codes: A61K 2800/5422 nonionic
• CPC Class Codes: A61K 2800/5424 anionic
• CPC Class Codes: A61K 8/0208 Tissues; Wipes; Patches
• CPC Class Codes: A61K 8/042 Gels
• CPC Class Codes: A61K 8/22 Peroxides; Oxygen; Ozone
• CPC Class Codes: A61K 8/73 Polysaccharides
• CPC Class Codes: A61K 8/731 Cellulose; Quaternized cellulose derivatives
• CPC Class Codes: A61K 8/8152 Homopolymers or copolymers of esters, e.g. (meth)acrylic acid esters; Compositions of derivatives of such polymers
• CPC Class Codes: A61K 8/817 Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen; Compositions or derivatives of such polymers, e.g. vinylimidazol, vinylcaprolactame, allylamines (Polyquaternium 6)
• CPC Class Codes: A61K 8/8176 Homopolymers of N-vinyl-pyrrolidones. Compositions of derivatives of such polymers
• CPC Class Codes: A61K 8/86 Polyethers
• CPC Class Codes: A61L 15/24 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof A61L15/225 takes precedence
• CPC Class Codes: A61L 15/26 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof A61L15/225 takes precedence
• CPC Class Codes: A61L 15/28 Polysaccharides or their derivatives A61L15/225 takes precedence
• CPC Class Codes: A61L 15/44 Medicaments
• CPC Class Codes: A61L 15/58 Adhesives
• CPC Class Codes: A61L 15/60 Liquid-swellable gel-forming materials, e.g. super-absorbents
• CPC Class Codes: A61L 26/0052 Mixtures of macromolecular compounds
• CPC Class Codes: A61Q 11/00 : Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
• CPC Class Codes: B05D 5/00 : Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures
• CPC Class Codes: C08L 53/00 : Compositions of block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers

Abstract

Hydrogel compositions are provided (a) that have a continuous hydrophobic phase and a discontinuous hydrophilic phase, (b) that have a discontinuous hydrophilic phase and a continuous hydrophilic phase, or (c) that are entirely composed of a continuous hydrophilic phase. The hydrophobic phase, if present, is composed of a hydrophobic polymer, particularly a hydrophobic pressure-sensitive adhesive (PSA), a plasticizing elastomer, a tackifying resin, and an optional antioxidant. The discontinuous hydrophilic phase, if present, is composed of a crosslinked hydrophilic polymer, particularly a crosslinked cellulosic polymer such as crosslinked sodium carboxymethylcellulose. For those hydrogel compositions containing a continuous hydrophilic phase, the components of the phase include a cellulose ester composition or an acrylate polymer or copolymer, and a blend of a hydrophilic polymer and a complementary oligomer capable of hydrogen bonding thereto. Films prepared from hydrogel compositions containing or entirely composed of the aforementioned continuous hydrophilic phase can be made translucent, and may be prepared using either melt extrusion or solution casting. A preferred use of the hydrogel compositions is in wound dressings, although numerous other uses are possible as well.

Claims

1. A hydrogel composition comprised of a discontinuous hydrophobic phase and a hydrophilic phase, wherein:

(a) the discontinuous hydrophobic phase comprises (i) a hydrophobic polymer, (ii) a plasticizer, (iii) a tackifying resin, and (iv) an optional antioxidant; and

(b) the hydrophilic phase is either discontinuous or continuous, wherein when the hydrophilic phase is continuous, the hydrophilic phase comprises a water-swellable cellulosic ester polymer composition that is insoluble in water at a pH of less than 8.5, or a water-swellable copolymer formed from two or more of acrylic acid, methacrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate, and ethyl methacrylate that is insoluble in water at a pH of less than 5.5.

2. The hydrogel composition of claim 1, wherein the hydrophilic phase is discontinuous.

3. The hydrogel composition of claim 2, wherein the hydrophilic phase is comprised of a crosslinked hydrophilic polymer that is insoluble in water.

4. The hydrogel composition of claim 3, wherein the water-swellable polymer is a crosslinked cellulosic polymer.

5. The hydrogel composition of claim 4, wherein the water-swellable polymer is crosslinked sodium carboxymethylcellulose.

6. The hydrogel composition of claim 1, wherein the hydrophilic phase is continuous.

7. The hydrogel composition of claim 6, wherein the hydrophilic phase further comprises:

(a) a blend of a hydrophilic polymer and a complementary oligomer capable of hydrogen bonding thereto; and

(b) an optionally added low molecular weight plasticizer.

12. The hydrogel composition of claim 7, wherein the water-swellable polymer is selected from polymers and copolymers of acrylic acid, methacrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate, and/or ethyl methacrylate.

13. The hydrogel composition of claim 12, wherein the water-swellable polymer is a copolymer of methacrylic acid and methyl methacrylate.

14. The hydrogel composition of claim 13, wherein the copolymer has a ratio of free carboxyl groups to ester groups in the range of about 1:

1 to 1;

2.

15. The hydrogel composition of claim 7, wherein the hydrophilic polymer is selected from the group consisting of poly(N-vinyl lactams), poly(N-vinyl amides), poly(N-alkylacrylamides), polyacrylic acid, polymethacrylic acid, polyvinyl alcohol, polyvinylamine, and copolymers and blends thereof.

22. The hydrogel composition of claim 7, wherein the hydrophilic polymer has a number average molecular weight in the range of approximately 100,000 to 2,000,000.

23. The hydrogel composition of claim 22, wherein the hydrophilic polymer has a number average molecular weight in the range of approximately 500,000 to 1,500,000.

24. The hydrogel composition of claim 7, wherein the complementary oligomer has a molecular weight in the range of about 45 to 800.

25. The hydrogel composition of claim 24, wherein the complementary oligomer has a molecular weight in the range of about 45 to 600.

26. The hydrogel composition of claim 24, wherein the complementary oligomer has a molecular weight in the range of about 300 to 600.

27. The hydrogel composition of claim 24, wherein the complementary oligomer is selected from the group consisting of polyalcohols, monomeric and oligomeric alkylene glycols, polyalkylene glycols, carboxyl-teminated polyalkylene glycols, amino-terminated polyalkylene glycols, ether alcohols, alkane diols and carbonic diacids.

28. The hydrogel composition of claim 27, wherein the complementary oligomer is selected from the group consisting of polyalkylene glycols and carboxyl-terminated polyalkylene glycols.

29. The hydrogel composition of claim 28, wherein the complementary oligomer is selected from the group consisting of polyethylene glycol and carboxyl-terminated polyethylene glycol.

30. The hydrogel composition of claim 28, wherein the complementary oligomer is polyethylene glycol.

31. The hydrogel composition of claim 30, wherein the complementary oligomer is polyethylene glycol 400.

32. The hydrogel composition of claim 7, wherein the low molecular weight plasticizer is selected from the group consisting of dialkyl phthalates, dicycloalkyl phthalates, diaryl phthalates, mixed alkyl-aryl phthalates, alkyl phosphates, aryl phosphates, alkyl citrates, citrate esters, alkyl adipates, dialkyl tartrates, dialkyl sebacates, dialkyl succinates, alkyl glycolates, alkyl glycerolates, glycol esters, glycerol esters, and mixtures thereof.

33. The hydrogel composition of claim 32, wherein the low molecular weight plasticizer is selected from the group consisting of dimethyl phthalate, diethyl phthalate, dipropyl phthalate, di(2-ethylhexyl)phthalate, di-isopropyl phthalate, diamyl phthalate, dicapryl phthalate, tributyl phosphate, trioctyl phosphate, tricresyl phosphate, triphenyl phosphate, trimethyl citrate, triethyl citrate, tributyl citrate, acetyl triethyl citrate, trihexyl citrate, dioctyl adipate, diethyl adipate, di(2-methylethyl)adipate, dihexyl adipate, diethyl tartrate, dibutyl tartrate, diethyl sebacate, dipropyl sebacate, dinonyl sebacate, diethyl succinate, dibutyl succinate, glycerol diacetate, glycerol triacetate, glycerol monolactate diacetate, methyl phthalyl ethyl glycolate, butyl phthalyl butyl glycolate, ethylene glycol diacetate, ethylene glycol dibutyrate, triethylene glycol diacetate, triethylene glycol dibutyrate, triethylene glycol dipropionate, and mixtures thereof.

34. The hydrogel composition of claim 33, wherein the low molecular weight plasticizer is dioctyl adipate.

35. The hydrogel composition of claim 1, wherein the optional antioxidant is present.

36. The hydrogel composition of claim 35, wherein the antioxidant is a sterically hindered phenol.

37. The hydrogel composition of claim 1, wherein the hydrophobic polymer is a hydrophobic pressure-sensitive adhesive.

38. The hydrogel composition of claim 37, wherein the hydrophobic polymer is selected from the group consisting of crosslinked butyl rubbers, natural rubber adhesives, vinyl ether polymers, polysiloxanes, polyisoprene, isobutylene-isoprene copolymers, butadiene acrylonitrile rubber, polychloroprene, atactic polypropylene, ethylene-propylene-diene terpolymers, and combinations thereof.

39. The hydrogel composition of claim 38, wherein the hydrophobic polymer is a crosslinked butyl rubber.

40. The hydrogel composition of claim 1, wherein the plasticizer is an elastomeric polymer.

41. The hydrogel composition of claim 40, wherein the elastomeric polymer is a styrene-based plasticizer selected from the group consisting of styrene-isoprene block copolymers, styrene-butadiene block copolymers, styrene-isoprene-styrene block copolymers, styrene-butadiene-styrene block copolymers, and combinations thereof.

42. The hydrogel composition of claim 7, wherein the hydrophilic polymer is crosslinked.

43. The hydrogel composition of claim 1, further including an active agent.

44. The hydrogel composition of claim 1, further including at least one additive selected from the group consisting of fillers, preservatives, pH regulators, softeners, thickeners, pigments, dyes, refractive particles, stabilizers, toughening agents and detackifiers.

45. The hydrogel composition of claim 7, wherein the relative quantities of the water-swellable polymer, the low molecular weight plasticizer, the hydrophilic polymer, and the complementary oligomer are selected so as to render the hydrogel composition translucent.

46. The hydrogel composition of claim 45, wherein the water-swellable polymer represents approximately 2 wt. % to approximately 15 wt. % of the hydrogel composition, the hydrophilic polymer and the complementary oligomer together represent approximately 17.5 wt. % to approximately 45 wt. % of the hydrogel composition, the low molecular weight plasticizer represents approximately 2.5 wt. % to approximately 5.0 wt. % of the hydrogel composition, and the weight ratio of the hydrophilic polymer to the complementary oligomer is in the range of about 70:

30 to about 40;

60.

47. The hydrogel composition of claim 1, further including an amount of an ionically conductive electrolyte effective to render the composition electrically conductive.

48. A wound dressing comprising a laminated composite of a body facing layer having a body-contacting surface, and an outwardly facing backing layer, wherein at least a portion of the body-contacting surface is comprised of the hydrogel composition of claim 1.

49. The wound dressing of claim 48, wherein the entire body-contacting surface is comprised of the hydrogel composition.

50. The wound dressing of claim 48, wherein the body-facing layer has a perimeter comprised of a skin-contact adhesive and an inner region containing the hydrogel composition.

51. The wound dressing of claim 50, wherein a central, wound-contacting portion of the inner region is comprised of the hydrogel composition.

52. The wound dressing of claim 48, wherein the backing layer is nonocclusive.

53. The wound dressing of claim 48, wherein the backing layer is occlusive.

54. The wound dressing of claim 48, further including a pressure-sensitive adhesive layer between the body-facing layer and the backing layer.

55. The wound dressing of claim 48, further including a removable release liner covering and co-extensive with the body-facing surface.

56. The wound dressing of claim 48, further including an active agent suitable for application to a wound.

57. The wound dressing of claim 56, wherein the active agent is selected from the group consisting of bacteriostatic and bactericidal compounds, antibiotic agents, pain relieving agents, topical vasodilators, tissue-healing enhancing agents, amino acids, proteins, proteolytic enzymes, cytokines, and polypeptide growth factors.

60. In a transdermal drug delivery device comprised of a drug reservoir, an outwardly facing backing layer, and a means for affixing the device to a body surface, the improvement which comprises employing the hydrogel of claim 1 as the drug reservoir, the affixing means, or both.

61. The transdermal drug delivery device of claim 60, wherein the drug reservoir serves as the affixing means.

62. In a pressure-relieving cushion for application to the body surface wherein the cushion is comprised of an outwardly facing backing layer and a body-facing layer of a crosslinked pressure-sensitive adhesive, the improvement comprising employing the hydrogel composition of claim 43 as the crosslinked pressure-sensitive adhesive.

8. The hydrogel composition of claim 8, wherein the cellulosic polymer composition is comprised of at least one cellulosic polymer containing unesterified cellulose units, cellulose acetate units, and either cellulose butyrate units or cellulose propionate units.

9. The hydrogel composition of claim 8, wherein the cellulosic polymer is cellulose acetate butyrate.

10. The hydrogel composition of claim 8, wherein the cellulosic polymer is cellulose acetate propionate.

11. The hydrogel composition of claim 8, wherein the cellulose ester composition comprises a mixture of cellulose acetate butyrate and cellulose acetate propionate.

16. The hydrogel composition of claim 16, wherein the hydrophilic polymer is selected from the group consisting of poly(N-vinyl lactams), poly(N-vinyl amides), poly(N-alkylacrylamides), and copolymers and blends thereof.

17. The hydrogel composition of claim 16, wherein the hydrophilic polymer is a poly(N-vinyl lactam).

18. The hydrogel composition of claim 17, wherein the hydrophilic polymer is a poly(N-vinyl lactam) homopolymer.

19. The hydrogel composition of claim 17, wherein the poly(N-vinyl lactam) is selected from the group consisting of polyvinyl pyrrolidone, polyvinyl caprolactam, and blends thereof.

20. The hydrogel composition of claim 19, wherein the poly(N-vinyl lactam) is polyvinyl pyrrolidone.

21. The hydrogel composition of claim 19, wherein the poly(N-vinyl lactam) is polyvinyl caprolactam.

58. A wound dressing having a translucent inner region for viewing a covered wound, comprising a substrate having:

a body facing surface;

an outwardly facing surface;

a peripheral skin contact adhesive on the body facing-surface providing means for affixing the wound dressing to a body surface in the region of a wound;

a translucent inner region; and

,

contained within the translucent inner region and on the body-facing surface of the wound dressing, a translucent hydrogel composition for absorbing wound exudate located within a central wound-contacting portion of the wound dressing.

59. The wound dressing of claim 58, wherein the translucent hydrogel comprises:

(a) a water-swellable polymer that is insoluble in water at a pH of less than 8.5; and

(b) a blend of a hydrophilic polymer and a complementary oligomer capable of hydrogen bonding to the hydrophilic polymer,

wherein the relative quantities of the water-swellable polymer, the hydrophilic polymer, and the complementary oligomer are selected so as to render the hydrogel translucent.

63. A method of forming a hydrogel film having a discontinuous hydrophobic phase comprising a hydrophobic polymer, a plasticizing elastomer, a tackifying resin, and an optional antioxidant, and a hydrophilic phase that is either discontinuous or continuous, wherein the method comprises:

melt processing the components of the hydrophobic and hydrophilic phases through an extruder to form an extruded hydrogel composition;

placing the extruded hydrogel composition on a substrate; and

applying pressure to the hydrogel layer to form a hydrogel film on the substrate.

64. The method of claim 63, wherein the components of the hydrophilic phase are added to the extruder prior to the components of the hydrophobic phase.

65. The method of claim 64, further comprising removing the hydrogel film from the substrate.