CA2450668A1 - Wound dressing and method for controlling severe, life-threatening bleeding - Google Patents

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

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Publication number
CA2450668A1
CA2450668A1 CA002450668A CA2450668A CA2450668A1 CA 2450668 A1 CA2450668 A1 CA 2450668A1 CA 002450668 A CA002450668 A CA 002450668A CA 2450668 A CA2450668 A CA 2450668A CA 2450668 A1 CA2450668 A1 CA 2450668A1
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Prior art keywords
wound
wound dressing
chitosan
severe
biomaterial
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Granted
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CA002450668A
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French (fr)
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CA2450668C (en
Inventor
Simon Mccarthy
Kenton W. Gregory
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Providence Health System Oregon
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Individual
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/425—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/32—Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/00987—Apparatus or processes for manufacturing non-adhesive dressings or bandages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/00987—Apparatus or processes for manufacturing non-adhesive dressings or bandages
    • A61F13/00991—Apparatus or processes for manufacturing non-adhesive dressings or bandages for treating webs, e.g. for moisturising, coating, impregnating or applying powder
    • A61F13/00995—Apparatus or processes for manufacturing non-adhesive dressings or bandages for treating webs, e.g. for moisturising, coating, impregnating or applying powder for mechanical treatments
    • A61F13/01012—
    • A61F13/01034—
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/15—Absorbent pads, e.g. sanitary towels, swabs or tampons for external or internal application to the body; Supporting or fastening means therefor; Tampon applicators
    • A61F13/15203—Properties of the article, e.g. stiffness or absorbency
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/28—Polysaccharides or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F2013/00089—Wound bandages
    • A61F2013/00106—Wound bandages emergency bandages, e.g. for first aid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F2013/00361—Plasters
    • A61F2013/00365—Plasters use
    • A61F2013/00463—Plasters use haemostatic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F2013/00361—Plasters
    • A61F2013/00365—Plasters use
    • A61F2013/00463—Plasters use haemostatic
    • A61F2013/00468—Plasters use haemostatic applying local pressure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F2013/00361—Plasters
    • A61F2013/00365—Plasters use
    • A61F2013/00463—Plasters use haemostatic
    • A61F2013/00472—Plasters use haemostatic with chemical means
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F2013/00361—Plasters
    • A61F2013/00365—Plasters use
    • A61F2013/00536—Plasters use for draining or irrigating wounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F2013/00361—Plasters
    • A61F2013/00365—Plasters use
    • A61F2013/0054—Plasters use for deep wounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F2013/00361—Plasters
    • A61F2013/00902—Plasters containing means
    • A61F2013/00927—Plasters containing means with biological activity, e.g. enzymes for debriding wounds or others, collagen or growth factors
    • A61F2013/00931—Plasters containing means with biological activity, e.g. enzymes for debriding wounds or others, collagen or growth factors chitin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/04—Materials for stopping bleeding

Abstract

This invention is directed to advanced hemorrhage control wound dressings, a nd methods of using a producing same. The subject wound dressing is constructed from a non-mammalian material for control of severe bleeding. The wound dressing is formed of a biomaterial comprising chitosan for controlling seve re bleeding. 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 t he subject wound. The wound dressing being capable of substantially stanching t he flow of the severe life-threatening bleeding from the wound by adhering to t he wound site, to seal the wound, to accelerate blood clot formation at the wou nd site, to reinforce clot information 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 (60)

1. A wound dressing which is formed of a biomaterial comprising chitosan, for controlling severe, life-threatening bleeding from a wound at a wound site of a person, said wound dressing being capable of substantially stanching the flow of said severe life-threatening bleeding from said wound by adhering to said wound site, to seal said wound, to accelerate blood clot formation at said wound site, to reinforce clot formation at said wound site and prevent bleed out from said wound site, and to substantially prohibit the flow of blood out of the said wound site.
2. The wound dressing of claim 1, wherein said severe, life-threatening bleeding is not capable of being stanched when a conventional gauze wound dressing is applied with conventional pressure to wound.
3. The wound dressing of claim 1, wherein said severe, life-threatening bleeding is not capable of being stanched when a conventional gauze wound dressing is applied with conventional pressure to wound and, if not controlled by other means, would result in the person lapsing into a state of hypotension.
4. The wound dressing of claim 1, wherein said severe, life-threatening bleeding is not capable of being stanched when a conventional gauze wound dressing is applied with conventional pressure to wound and, if not controlled by other means, would result in the systolic blood pressure of the person dropping to a level of less than about 90 mm Hg.
5. The wound dressing of claim 1, wherein said biomaterial comprises a non-mammalian material.
6. The wound dressing of claim 1, wherein said severe bleeding is a steady high flow of blood of more than about 90 ml of blood loss per minute, such that in about 20 minutes of bleeding a volume of more than about 40% of total blood from a 70 kg human male would be lost, said blood volume loss greatly reducing the likelihood of survival of the wounded person.
7. The wound dressing of claim 1, which is capable of stanching said severe bleeding which is caused by a substantial arterial wound or a substantial venous wound having a blood flow rate of at least about 90 ml/minute.
8. The wound dressing of claim 1, which is sterilized by gamma irradiation
9. The wound dressing of claim 1, which has antiseptic properties.
10. The wound dressing of claim 1, which prohibits the flow of blood And other fluids into said wound site.
11. The wound dressing of claim 1, which has an ultimate tensil breaking load of not less than about 1 kg.
12. The wound dressing of claim 1, which has an ultimate elongation of at least about 70%.
13. The wound dressing of claim 1, which has Young's modulus which Is less than about 5 MPa.
14. The wound dressing of claim 1, wherein said severe bleeding is caused by a ballistic projectile injury or a sharp perforation injury or a blunt traumatic injury.
15. The wound dressing of claim 1, wherein said biomaterial is formed by a freeze drying, non-woven spinning, conventional spinning, electro-spinning, freeze substitution, phase inversion solvent process, solution coating or a combination thereof.
16. The wound dressing of claim 1, which is capable of adhering to said wound site by the application of direct pressure to the wound dressing for a period of time of not more than about five minutes.
17. The wound dressing of claim 1, which facilitates substantial clotting and agglutinating of the severe bleeding from the wound site and stanches said severe bleeding which includes the temporary application of direct pressure to the wound dressing.
18. The wound dressing of claim 1, wherein said biomaterial comprises interconnected open porous structure, and/or an oriented open lamella structure, and/or an open tubular structure, and/or an open honeycomb structure, and/or a filamentous structure.
19. The wound dressing of claim 1, which has an available blood contacting surface area per base surface of said wound dressing of at least about 100 cm2 per cm2.
20. The wound dressing of claim 1, which has a mean rate of dissolution per base surface area of said wound dressing when adhered to said wound site, at a temperature of about 37°C, of not more than about 0.008 grams per min per cm2.
21. The wound dressing of claim 1, which has a density of at least about 0.05 g/cm3.
22. The wound dressing of claim 1, which has a number average molecular weight of at least about 50 kda, and a weight average molecular weight of at least about 100 kda.
23. The wound dressing of claim 1, which has a Brookfield LV DV-II+
viscosity of not less than about 100 cps.
24. The wound dressing of claim 1, which has an open pore diameter of at least about 15 microns up to about 150 microns.
25. The wound dressing of claim 1, which has a backing support layer attached thereto.
26. The wound dressing of claim 25, wherein the backing support layer is substantially blood insoluble and non-sticking to hands or gloves.
27. The wound dressing of claim 25, wherein the backing support layer is substantially blood impermeable.
28. The wound dressing of claim 1, wherein the degree of adhesion of the wound dressing to the wound site is at least about 40 kPa.
29. The wound dressing of claim 1, which comprises cationic chitosan salts for promoting tissue adhesion and tissue sealing.
30. The wound dressing of claim 1, which has an available mass of chitosan biomaterial per wound surface area which is at least about 0.02g/cm2.
31. The wound dressing of claim 29, wherein said cationic chitosan salts are selected from a group consisting of chitosan formate, chitosan acetate, chitosan lactate, chitosan ascorbate, chitosan chloride and chitosan citrate.
32. The wound dressing of claim 1, wherein the chitosan has a degree of deacetylation of at least about 70%.
33. The wound dressing of claim 1, wherein the thickness of the biomaterial is not less than about 3.0 mm and not more than about 8.0 mm.
34. The wound dressing of claim 1, wherein said severe bleeding is caused by coagulopathy or internal trauma or surgical trauma.
35. The wound dressing of claim 1, which further includes a supplemental traction surface.
36. The wound dressing of claim 35, wherein said supplemental traction surface is in the form of a tread design.
37. The wound dressing of claim 1, which is capable of forming an adhesive material in combination with blood flowing from said wound at the wound dressing-blood interface, said adhesive material having a pH of not more than about 5 when the wound is sealed.
38. The wound dressing of claim 37, wherein the acid employed to adjust the pH of the adhesive material is selected from a group consisting of acetic acid, formic acid, lactic acid, ascorbic acid, hydrochloric acid, and citric acid.
39. The wound dressing of claim 37, wherein the mole ratio of acid anion to glucosamine functional groups in the chitosan cation/anion pair required to adjust the pH to the level described above is preferably about 0.9.
40. The wound dressing of claim 1, which is capable of being conformed to the configuration of the wound for engagingly contacting said wound and facilitating stanching of the flow of said severe life-threatening bleeding.
41. The wound dressing of claim 40, which is capable of being conformed into a tubular configuration and inserted into said wound.
42. A method for controlling severe, life-threatening bleeding from a wound at a wound site of a person, which comprises providing a wound dressing formed of a biomaterial comprising chitosan, adhering said wound dressing to said wound site and substantially stanching the flow of said severe life-threatening bleeding from said wound, sealing said wound and preventing bleed out from said wound site, and preventing bleeding and the flow of other fluids into and/or out of the said wound site, said bleeding not capable of being stanched when a conventional gauze bandage is used for purposes of stanching said severe, life-threatening bleeding.
43. A method for producing a wound dressing capable of controlling severe, life-threatening bleeding from a wound at a wound site of a person, comprising providing a chitosan biomaterial;
degassing said chitosan biomaterial; and freezing said chitosan biomaterial; and forming a wound dressing from said frozen chitosan biomaterial, said wound dressing being capable of substantially stanching the flow of said severe life-threatening bleeding from said wound by adhering to said wound site, to seal said wound and prevent bleed out from said wound site, and to prevent the flow of bleeding and other fluids into and/or out of the said wound site, said severe, life-threatening bleeding not capable of being stanched when a conventional gauze bandage is applied to the wound site.
44. The method of claim 43, which further includes the step of freeze-drying said frozen chitosan biomaterial.
45. The method of claim 43, which further includes the step of heating said frozen biomaterial.
46. The method of claim 43, which further includes the step of compressing said wound dressing to reduce the thickness and increase the density of said wound dressing thereby increasing the adhesion strength and dissolution resistance of said wound dressing.
47. The method of claim 43, which further includes the step of irradiating said wound dressing to sterilize and improve mechanical, wetting and adhesion properties thereof.
48. The method of claim 43, wherein said degassing step comprises removing sufficient residual gas from the chitosan biomaterial so that, on undergoing a subsequent freezing operation, the gas does not escape and form unwanted voids or trapped gas bubbles in the subject wound dressing product.
49. The method of claim 43, wherein said degassing step comprises heating said chitosan biomaterial, and then applying a vacuum thereto.
50. The method of claim 43, wherein the freezing step is carried out by cooling the chitosan biomaterial and lowering the temperature thereof from room temperature to a final temperature below the freezing point.
51. The method of claim 43, wherein freezing step is carried out by cooling the chitosan biomaterial and lowering the temperature thereof from room temperature to a final temperature of not more than about -10°C.
52. The method of claim 43, wherein freezing step is carried out by cooling the chitosan biomaterial so that the temperature is gradually lowered over a predetermined time period.
53. The method of claim 43, which further includes the step of removing water from within the interstices of the frozen chitosan biomaterial.
54. The method of claim 53, wherein the step of removing water from within the interstices of the frozen chitosan biomaterial is achieved without damaging the structural integrity of the frozen chitosan biomaterial.
55. The method of claim 53, wherein during the step of removing water from within the interstices of the frozen chitosan biomaterial the water passes from a solid frozen phase into a gas phase without the substantial formation of an intermediate liquid phase.
56. The method of claim 53, wherein the step of removing water from within the interstices of the frozen chitosan biomaterial comprises freeze drying, or freeze substitution or a combination thereof.
57. The method of claim 46, wherein the compression temperature in not less than about 60°C.
58. The method of claim 46, wherein the compressed chitosan biomaterial is preconditioned by heating same to a temperature of preferably up to about 75°C.
59. The method of claim 46, wherein said preconditioning step is typically conducted for a period of time up to about 0.25 hours.
60. The method of claim 46, which further includes the step of irradiating the wound dressing at a level of at least about 5 kGy.
CA2450668A 2001-06-14 2002-06-14 Wound dressing and method for controlling severe, life-threatening bleeding Expired - Fee Related CA2450668C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US29877301P 2001-06-14 2001-06-14
US60/298,773 2001-06-14
PCT/US2002/018757 WO2002102276A2 (en) 2001-06-14 2002-06-14 Wound dressing and method for controlling severe, life-threatening bleeding

Publications (2)

Publication Number Publication Date
CA2450668A1 true CA2450668A1 (en) 2002-12-27
CA2450668C CA2450668C (en) 2010-05-04

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US (3) US7482503B2 (en)
EP (1) EP1401352B1 (en)
JP (1) JP4332030B2 (en)
KR (2) KR100953466B1 (en)
AT (1) ATE549996T1 (en)
AU (1) AU2002312493B2 (en)
BR (1) BR0210406A (en)
CA (1) CA2450668C (en)
DK (1) DK1401352T3 (en)
IL (2) IL159339A0 (en)
NO (1) NO325688B1 (en)
NZ (1) NZ530399A (en)
WO (1) WO2002102276A2 (en)
ZA (1) ZA200309861B (en)

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US7482503B2 (en) 2009-01-27

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