Wound dressing and method for controlling severe, life-threatening bleeding

• US 20040243043A1
• Filed: 12/23/2003
• Published: 12/02/2004
• Est. Priority Date: 06/14/2002
• Status: Active Grant

• Current Assignee: Providence Health System - Oregon
• Original Assignee: Providence Health System - Oregon
• Inventors: McCarthy, Simon J,, Campbell, Todd D., Wiesmann, William P., Gregory, Kenton W.
• Granted Patent: US 7,371,403 B2
• Time in Patent Office: Days
• US Class Current: 602/46
• CPC Class Codes: A61F 13/00063 comprising medicaments or additives, e.g. odor control, PH control, debriding, antimicrobic drug delivery dressings A61K9/70; chemical aspect of the additives A61L15/00
• CPC Class Codes: A61F 13/0203 with fluid retention members
• CPC Class Codes: A61F 13/0253 characterized by the adhesive material
• CPC Class Codes: A61F 13/0256 characterized by the parametric properties of the adhesive
• CPC Class Codes: A61F 13/0276 Apparatus or processes for manufacturing adhesive dressings or bandages
• CPC Class Codes: A61F 13/0289 manufacturing of adhesive dressings
• CPC Class Codes: A61F 13/36 Surgical swabs, e.g. for absorbency or packing body cavities during surgery A61F13/38 takes precedence
• CPC Class Codes: A61F 17/00 First-aid kits
• CPC Class Codes: A61F 2013/00106 emergency bandages, e.g. for first aid
• CPC Class Codes: A61F 2013/00221 biodegradable, non-irritating
• CPC Class Codes: A61F 2013/00463 haemostatic
• CPC Class Codes: A61F 2013/00468 applying local pressure
• CPC Class Codes: A61F 2013/00472 with chemical means
• CPC Class Codes: A61F 2013/0054 for deep wounds
• CPC Class Codes: A61F 2013/00659 polymeric base
• CPC Class Codes: A61F 2013/00676 hydrogel
• CPC Class Codes: A61F 2013/0071 containing active agent
• CPC Class Codes: A61F 2013/00719 adhesives for use on wounds
• CPC Class Codes: A61F 2013/00931 chitin
• CPC Class Codes: A61F 5/40 Suspensory bandages
• CPC Class Codes: A61L 15/28 : Polysaccharides or their derivatives A61L15/225 takes precedence
• CPC Class Codes: A61L 15/425 : Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 2400/04 : Materials for stopping bleeding
• CPC Class Codes: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: C08L 1/00 : Compositions of cellulose, modified cellulose or cellulose derivatives
• CPC Class Codes: C08L 5/08 : Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

This invention is directed to advanced hemorrhage control wound dressings, and methods of using and producing same. The subject wound dressing is constructed from a non-mammalian material for control of severe bleeding. The wound dressing for controlling severe bleeding is formed of a biomaterial comprising chitosan, a hydrophilic polymer, a polyacrylic polymer or a combination thereof. The kind of severe, life-threatening bleeding contemplated by this invention is typically of the type not capable of being stanched when a conventional gauze wound dressing is applied with conventional pressure to the subject wound. The wound dressing being capable of substantially stanching the flow of the severe life-threatening bleeding from the wound by adhering to the wound site, to seal the wound, to accelerate blood clot formation at the wound site, to reinforce clot formation at the wound site and prevent bleed out from the wound site, and to substantially prohibit the flow of blood out of the wound site.

Claims

1. A compressed sponge for hemorrhage control comprising a hydrophilic polymer, wherein the compressed sponge has a compressed sponge density of about 0.6 to 0.15 g/cm³.

2. The compressed sponge of claim 1, wherein the hydrophilic polymer is an alginate, chitosan, a hydrophilic polyamine, a chitosan derivative, polylysine, polyethylene imine, xanthan, carrageenan, quaternary ammonium polymer, chondroitin sulfate, a starch, a modified cellulosic polymer, a dextran, hyaluronan or a combination thereof.

3. The compressed sponge of claim 2, wherein the starch is selected from the group consisting of amylase, amylopectin and a combination of amylopectin and amylase.

4. The compressed sponge of claim 1, wherein the hydrophilic polymer is chitosan.

5. The compressed sponge of claim 4, wherein the chitosan has a weight average molecular weight of at least about 100 kDa.

6. The compressed sponge of claim 4, wherein the chitosan has a weight average molecular weight of at least about 150 kDa.

7. The compressed sponge of claim 4, wherein the chitosan has a weight average molecular weight of at least about 300 kDa.

8. The compressed sponge of claim 4, wherein the chitosan has a viscosity at 25°

C. in a 1% solution of acetic acid (AA) which is about 100 centipoise to about 2000 centipoise.

9. The compressed sponge of claim 4, wherein the chitosan has viscosity at 25°

C. in a 1% solution of acetic acid (AA) which is about 125 centipoise to about 1000 centipoise.

10. The compressed sponge of claim 4, wherein the chitosan has viscosity at 25°

C. in a 1% solution of acetic acid (AA) which is about 150 centipoise to about 500 centipoise.

11. The compressed sponge of claim 1, wherein the compressed sponge further comprises an active ingredient.

12. The compressed sponge of claim 11, wherein the active ingredient is selected from the group consisting of calcium, thrombin, factor VIIa, factor XIII, thromboxane A2, prostaglandin-2a, epidermal growth factor, platelet derived growth factor, Von Willebrand factor, tumor necrosis factor (TNF), TNF-alpha, transforming growth factor (TGF), TGF-alpha, TGF-beta, insulin like growth factor, fibroblast growth factor, keratinocyte growth factor, nerve growth factor, penicillin, ampicillin, methicillin, amoxycillin, clavamox, clavulanic acid, amoxicillin, aztreonam, imipenem, streptomycin, Kanamycin, Tobramycin, gentamicin, vancomycin, clindamycin, erythromycin, polymyxin, bacitracin, amphotericin, nystatin, rifampicin, tetracycline, doxycycline, chloramphenicol and a combination thereof.

66. A process for preparing a compressed sponge of claim 1 for hemorrhage control comprising:

(a) freezing/freeze drying a low density sponge; and

(b) compressing the low density sponge at a preferred rate of 10 mm per minute and at a preferred controlled temperature of 80°

C. thereby obtaining a compressed sponge with a density of about 0.1 to about 0.2 g/cm³.

67. A process for preparing a compressed sponge for hemorrhage control of claim 1 comprising:

(a) compressing the subsequent low density sponge at a rate of about 10 mm per minute, at a controlled temperature of 80°

C. to obtain a compressed sponge with a density of about 0.1 to about 0.2 g/cm³, and wherein said low density sponge has not been frozen or freeze dried prior to compressing.

68. The process of claim 67, wherein the low density sponge has a density of about 0.010 g/cm³ to about 0.035 g/cm³.

69. The process of claim 67, wherein the compressed sponge has a density of about 0.1 g/cm³ to about 0.15 g/cm³.

79. A method of preventing severe bleeding in a subject comprising administering a compressed sponge of claim 1 or a compressed composite sponge of claim 13 to said subject in need thereof.

80. The method of claim 79, wherein the subject is a mammal.

81. The method of claim 79, wherein the mammal is human.

82. The method of claim 79, wherein the subject is suffering from severe bleeding such that about 30-40% total blood loss would result within 20 to 30 minutes if the bleeding was left uncontrolled.

83. The method of claim 79, wherein the compressed sponge or compressed composite sponge is applied with about 60 to 80 kPa pressure directly over the bleeding injury and held in place for 3 to 5 minutes before releasing, packing and wrapping.

84. A bandage kit for treating severe bleeding comprising compressed sponges of claim 1 or a composite compressed sponge of claim 13, gauze rolls for packing, and an Ace bandage for wrapping a wound.

85. A process for mechanical mating and meshing of the sponges of claims 1 and 13 comprising pressing tissue contacting sides of the sponge against a microtextured surface.

86. The process of claim 85, wherein the microtextured surface is selected from the group consisting of surfaces prepared by chemical etching, surfaces prepared by ion beam surface ablation, surfaces prepared by mechanical cutting, and surfaces prepared by laser ablation.

87. A process for improving the mechanical traction of the sponges of claims 1 and 13 comprising pressing tissue contacting sides of the sponge against a microtextured surface.

88. The process of claim 87, wherein the microtextured surface is selected from the group consisting of surfaces prepared by chemical etching, and surfaces prepared by particle blasting techniques.

89. A process for limiting or stopping the formation of coarse crust on the surface of the sponges of claims 1 and 13 comprising covering the surface of the sponge with a polymer film, a polymer plate, an elevated plastic plate or a moisture impermeable, breathable membrane film.

92. The compressed sponge and compressed composite sponge of claims 1 and 13, wherein the sponges further comprise at least one additional hydrophilic polymer.

93. The compressed sponge and compressed composite sponge of claim 92, wherein the hydrophilic polymer is selected from the group consisting of alginate, chitosan, a hydrophilic polyamine, a chitosan derivative, polylysine, polyethylene imine, xanthan, carrageenan, quaternary ammonium polymer, chondroitin sulfate, a starch, a modified cellulosic polymer, a dextran, hyaluronan and a combination thereof.

94. The compressed sponge of claim 93, wherein the starch is selected from the group consisting of amylase, amylopectin, and a combination of amylopectin and amylase.

95. The compressed sponge of claim 92, wherein the hydrophilic polymer is chitosan.

13. A compressed composite sponge for hemorrhage control comprising a hydrophilic polymer sponge and a wettable polymer matrix or wettable polymer matrices inside the sponge and/or at the sponge surface.

14. The compressed composite sponge of claim 13, wherein the hydrophilic polymer is selected from the group consisting ofalginate, a hydrophilic polyamine, a chitosan derivative, polylysine, polyethylene imine, xanthan, carrageenan, quaternary ammonium polymer, chondroitin sulfate, a starch, a modified cellulosic polymer, a dextran, hyaluronan and a combination thereof.

15. The compressed composite sponge of claim 14, wherein the starch is selected from the group consisting of amylase, amylopectin and a combination of both amylopectin and amylase.

16. The compressed composite sponge of claim 13, wherein the wettable polymer is selected from the group consisting of non-woven mats, woven mats, molded polymer mesh and lowdensity sponges.

17. The compressed composite sponge of claim 16, wherein the wettable polymer matrix is selected from the group consisting of a chitin, an alginate, a neutralized chitosan, a re-acetylated chitosan, a poly(glycolic acid), a poly(lactic acid), a poly(e-caprolactone), a poly(β

-hydroxybutyric acid), a poly(β

-hydroxyvaleric acid), a polydioxanone, a poly(ethylene oxide), a poly(malic acid), a poly(tartronic acid), a polyphosphazene, a polyethylene, a polypropylene, a metallocene polymer, a polyurethane, a polyvinylchloride polymer, a polyester, a polyamide and a combination thereof.

18. The compressed composite sponge of claim 13, wherein the hydrophilic polymer is chitosan.

19. The compressed composite sponge of claim 18, wherein the chitosan has a weight average molecular weight of at least about 100 kDa.

20. The compressed composite sponge of claim 18, wherein the chitosan has a weight average molecular weight of at least about 150 kDa.

21. The compressed composite sponge of claim 18, wherein the chitosan has a weight average molecular weight of at least about 300 kDa.

22. The compressed composite sponge of claim 18, wherein the chitosan has a viscosity at 25°

C. in a 1% solution of acetic acid (AA) which is about 100 centipoise to about 2000 centipoise.

23. The compressed composite sponge of claim 18, wherein the chitosan has viscosity at 25°

C. in a 1% solution of acetic acid (AA) which is about 125 centipoise to about 1000 centipoise.

24. The compressed composite sponge of claim 18, wherein the chitosan has viscosity at 25°

C. in a 1% solution of acetic acid (AA) which is about 150 centipoise to about 500 centipoise.

25. The compressed composite sponge of claim 13, wherein the sponge comprises a textile thread impregnated with a hydrophilic polymer.

26. The compressed composite sponge of claim 25, wherein the textile thread is impregnated with a hydrophilic polymer.

27. The compressed composite sponge of claim 26, wherein the hydrophilic polymer is chitosan.

28. The compressed composite sponge of claim 26, wherein the hydrophilic polymer is alginate, a hydrophilic polyamine, a chitosan derivative, polylysine, polyethylene imine, xanthan, carrageenan, quaternary ammonium polymer, chondroitin sulfate, a starch, a modified cellulosic polymer, a dextran, hyaluronan or acombination thereof.

29. The compressed composite sponge of claim 28, wherein the starch is selected from the group consisting of amylase, amylopectin and a combination of both amylopectin and amylase.

30. The compressed composite sponge of claim 13, wherein the wettable mesh is a non-woven mesh.

31. The compressed composite sponge of claim 13, wherein the sponge contains pores with pore diameters of about 15 microns to about 300 microns.

32. The compressed composite sponge of claim 13, wherein the sponge contains pores with pore diameters of about 30 microns to about 250 microns.

33. The compressed composite sponge of claim 13, wherein the sponge contains pores with pore diameters of about 100 microns to about 225 microns.

34. The compressed composite sponge of claim 13, wherein the sponge contains pores with pore diameters of about 125 microns to about 200 microns.

35. The compressed composite sponge of claim 13, wherein the sponge contains pores with pore diameters of about 150 microns to about 175 microns.

36. The compressed composite sponge of claim 13, wherein the sponge has an available blood contacting surface area per base surface of the sponge of about 100 cm² per cm² to about 1000 cm² per cm².

37. The compressed composite sponge of claim 13, wherein the sponge has an available blood contacting surface area per base surface of the sponge of about 200 cm² per cm² to about 800 cm² per cm².

38. The compressed composite sponge of claim 13, wherein the sponge has an available blood contacting surface area per base surface of the sponge of about 300 cm² per cm² to about 500 cm² per cm².

39. The compressed composite sponge of claim 18, wherein the available mass of chitosan biomaterial per wound surface area is about 0.02 g/cm² to about 1.0 g/cm².

40. The compressed composite sponge of claim 18, wherein the available mass of chitosan biomaterial per wound surface area is about 0.04 g/cm² about 0.5 g/cm².

41. The compressed composite sponge of claim 18, wherein the available mass of chitosan biomaterial per wound surface area is about 0.06 g/cm² about 0.1 g/cm².

42. The compressed composite sponge of claim 13, wherein the compressed composite sponge further comprises a backing support layer.

43. The compressed composite sponge of claim 42, wherein the backing support layer is a layer of polymeric material.

44. The compressed composite sponge of claim 43, wherein the polymeric material is a synthetic non-biodegradable material or a naturally occurring biodegradable polymer.

45. The compressed composite sponge of claim 44, wherein the synthetic biodegradable material is selected from the group consisting of poly(glycolic acid), poly(lactic acid), poly(e-caprolactone), poly(β

-hydroxybutyric acid), poly(β

-hydroxyvaleric acid), polydioxanone, poly(ethylene oxide), poly(malic acid), poly(tartronic acid), polyphosphazene, the copolymers of the monomers used to synthesize said polymers and combinations thereof.

46. The compressed composite sponge of claim 43, wherein the naturally occurring polymer is selected from the group consisting of chitin, algin, a starch, dextran, collagen, albumen, and a combination thereof.

47. The compressed composite sponge of claim 44, wherein the synthetic non-biodegradable material is selected from the group consisting of polyethylene, polypropylene, a metallocene polymer, a polyurethane, a polyvinylchloride polymer, a polyester and a polyamide.

48. The compressed composite sponge of claim 13, wherein the compressed composite sponge has a degree of adhesion to the wound site of about 40 kPa to about 500 kPa.

49. The compressed composite sponge of claim 13, wherein the compressed composite sponge has a degree of adhesion to the wound site of about 60 kPa to about 250 kPa.

50. The compressed composite sponge of claim 13, wherein the compressed composite sponge has a degree of adhesion to the wound site of about 100 kPa to about 200 kPa.

51. The compressed composite sponge of claim 13, wherein the compressed composite sponge is capable of forming an adhesive material in combination with blood flowing from said wound at a wound dressing-blood interface.

52. The compressed composite sponge of claim 51, wherein the adhesive material is a chitosan adhesive material.

53. The compressed composite sponge of claim 52, wherein the chitosan adhesive material preferably has a pH of not more than about 5.5 when the wound is sealed.

54. The compressed composite sponge of claim 52, wherein the chitosan adhesive material preferably has a pH of not more than about 4.5 when the wound is sealed.

55. The compressed composite sponge of claim 52, wherein the chitosan adhesive material preferably has a pH of not more than about 4.0 when the wound is sealed.

56. The compressed chitosan composite sponge of claim 52, wherein the adhesive material comprises an acid selected from the group consisting of acetic acid, formic acid, lactic acid, ascorbic acid, hydrochloric acid, and citric acid.

57. The compressed composite sponge of claim 13, wherein the compressed composite sponge has a thickness of not less than about 3.0 mm and not more than about 8 mm.

58. The compressed composite sponge of claim 13, wherein the compressed composite sponge has a thickness of not less than about 3.5 mm and not more than about 7 mm.

59. The compressed composite sponge of claim 13, wherein the compressed composite sponge has a thickness of not less than about 4.0 mm and not more than about 6 mm.

60. The compressed composite sponge of claim 13, wherein the compressed composite sponge has an ultimate tensile stress about 0.1 MPa to about 1.0 MPa.

61. The compressed composite sponge of claim 13, wherein the compressed composite sponge has an ultimate tensile stress of about 0.15 MPa to about 0.8 MPa.

62. The compressed composite sponge of claim 13, wherein the compressed composite sponge has an ultimate tensile stress of about 0.25 MPa to about 0.5 Mpa.

63. The compressed composite sponge of claim 13, wherein the compressed composite sponge has an ultimate elongation of about 5%.

64. The compressed composite sponge of claim 13, wherein the compressed composite sponge has an ultimate elongation of about 10%.

65. The compressed composite sponge of claim 13, wherein the compressed composite sponge has an ultimate elongation of about 15%.

70. A process for preparing a compressed composite sponge for hemorrhage control of claim 13 comprising:

a) degassing a chitosan biomaterial solution by heating the chitosan biomaterial solution and applying a vacuum thereto;

b) freezing the chitosan biomaterial solution;

c) removing water from within frozen chitosan biomaterial without damaging the structural integrity of the frozen chitosan biomaterial so that the water in the chitosan biomaterial passes from a solid phase into a gas phase;

d) compressing the chitosan biomaterial at a preferred rate of about 10 mm per minute thereby obtaining a compressed sponge with a density of about 0.1 to about 0.2 g/cm³; and

e) baking of the compressed chitosan sponge at about 80°

C. for about 30 minutes.

71. The process of claim 70, wherein the temperature is gradually lowered over a predetermined period of time during the freezing of the chitosan biomaterial of step (b).

72. The process of claim 70, wherein the temperature of step (b) is a final freezing temperature of not more than about −

25°

C.

73. The process of claim 70, wherein the temperature of step (b) is a final freezing temperature of not more than about −

35°

C.

74. The process of claim 70, wherein the temperature of step (b) is a final freezing temperature of not more than about −

45°

C.

75. The process of claim 70, wherein the water removal is performed by freeze-drying the frozen chitosan biomaterial.

76. The process of claim 70, further comprising the step of adding gases selected from the group consisting of argon, nitrogen and helium back into the degassed chitosan solution before the freezing.

77. The process of claim 70, wherein the compressed sponge is sterilized.

78. The process of claim 70, wherein the compressed sponge is sterilized by gamma irradiation.

90. A low density sponge, wherein the sponge is formed by compressing a sponge with a density of about less than 0.05 g/cm³ until said sponge reaches a density of about less than 0.08 g/cm³, and wherein the sponge is formed by a process other than freezing or freeze drying.

91. The low density sponge of claim 90, wherein the sponge is formed using a method selected from the group consisting of a phase inversion process, sponges prepared by covalent binding of active components to preformed matrices and by foaming techniques.