Alkylsulfonated polyaminosaccharides

• US 20050283004A1
• Filed: 06/18/2004
• Published: 12/22/2005
• Est. Priority Date: 06/18/2004
• Status: Abandoned Application

• Current Assignee: Taiwan Hopax Chemicals Manufacturing Company Limited
• Original Assignee: Taiwan Hopax Chemicals Manufacturing Company Limited
• Inventors: Lee, Kung-Hsing, Hung, Hsien-Ming, Wei, I-Chien
• Application Number:
  US10/871,890
• Publication Number:
  US 20050283004A1
• Time in Patent Office: Days
• US Class Current: 536/20
• CPC Class Codes: A61K 2800/75 Anti-irritant
• CPC Class Codes: A61K 8/736 Chitin; Chitosan; Derivatives thereof
• CPC Class Codes: A61L 15/28 Polysaccharides or their derivatives A61L15/225 takes precedence
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 17/16 Emollients or protectives, e.g. against radiation
• CPC Class Codes: A61P 31/02 Local antiseptics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61Q 17/04 Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: A61Q 19/007 Preparations for dry skin
• CPC Class Codes: C08B 37/003 Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

Alkylsulfonated polyaminosaccharides, such as alkylsulfonated chitosan, having a sultone substituent covalently bonded to the amino group and a known size and degree of substitution may be produced by methods of the invention. Such methods may include heating of the polyaminosaccharide in a polar solvent, such as alcohol, ether, or alcoholether to reflux, then adding an alkyl sultone. Alkylsulfonated polyaminosaccharides of the present invention may be used in a wide variety of applications. Alkylsulfonated chitosan is particularly useful in wound healing.

Claims

1. A method of making an alkylsulfonated polyaminosaccharide comprising:

adding a polyaminosaccharide to an organic solvent to form a mixture;

heating the mixture to a reflux temperature;

reacting an alkyl sultone with the polyaminosaccharide in the mixture to form a covalent bond between the alkyl sultone and an amino group of the polyaminosaccharide resulting in an alkylsulfonated polyaminosaccharide.

2. The method of claim 1, wherein the polyaminosaccharide further comprises a deacetylated polyaminosaccharide.

3. The method of claim 1, wherein the polyaminosaccharide has a molecular weight of between 300 and 200,000.

4. The method of claim 3, wherein the polyaminosaccharide has a molecular weight of between 3,000 and 140,000.

5. The method of claim 1, wherein the polyaminosaccharide comprises chitosan.

6. The method of claim 1, wherein the organic solvent comprises an alcohol, ether, or etheralcohol.

7. The method of claim 6, further comprising the alcohol, ether, or etheralcohol selected from the group consisting of:

methanol, ethanol, isopropanol, butanol, methoxypropanol and any combination thereof.

8. The method of claim 1, further comprising the reflux temperature between 50 and 150°

C.

9. The method of claim 1, further comprising the alkyl sultone having a formula of:

wherein R₁ is CH₂, CH or C₂H₄;

R₂ is CH or CH₂; and

R₃ is H or CH₃.

10. The method of claim 9, wherein R₁ is CH₂, R₂ is CH₂, and R₃ is H.

11. The method of claim 9, wherein R₁ is CH, R₂ is CH, and R₃ is H.

12. The method of claim 9, wherein R₁ is CH₂, R₂ is CH₂, and R₃ is CH₃.

13. The method of claim 9, wherein R₁ is C₂H₄, R₂ is CH₂, and R₃ is H.

14. The method of claim 1, further comprising the alkyl sultone selected from the group consisting of:

1,3-propane sultone, 1,3-propene sultone, 1,4-butane sultone, 2,4-butane sultone and any combination thereof.

15. The method of claim 1, further comprising the alkylsulfonated polyaminosaccharide having a known degree of substitution with the alkyl sultone.

16. The method of claim 15, further comprising a degree of substitution between 10% and 80%.

17. The method of claim 15, further comprising a degree of substitution between 5% and 60%.

18. The method of claim 15, further comprising a degree of substitution between 30% and 40%.

19. The method of claim 1, further comprising the mixture having a mole ratio of polyaminosaccharide to alkyl sultone of between 1:

4 and 4;

1.

20. The method of claim 1, further comprising the mixture having a mole ratio of polyaminosaccharide to alkyl sultone of between 1:

2 and 2;

1.

21. The method of claim 1, further comprising precipitating the alkylsulfonated polyaminosaccharide.

22. The method of claim 21, further comprising collecting the precipitated alkylsulfonated polyaminosaccharide by filtration.

23. The method of claim 21, further comprising crystallizing the alkylsulfonated polyaminosaccharide.

24. The method of claim 1, further comprising obtaining a reaction yield of at least 50%.

25. The method of claim 1, further comprising obtaining a reaction yield of at least 80%.

26. The method of claim 1, further comprising obtaining a reaction yield of at least 99%.

27. A method of making an alkylsulfonated chitosan comprising:

adding a chitosan to an organic solvent to form a mixture;

heating the mixture to a reflux temperature;

reacting an alkyl sultone with the chitosan in the mixture to form a covalent bond between an alkyl sultone and an amino group of the chitosan resulting in an alkylsulfonated chitosan.

28. The method of claim 27, wherein the chitosan is selected from the group consisting of:

α

chitosan, β

chitosan, linear chitosan, branched chitosan and any combination thereof.

29. The method of claim 27, further comprising the organic solvent selected from the group consisting of:

methanol, ethanol, isopropanol, butanol, methoxypropanol and any combination thereof.

30. The method of claim 27, further comprising the reflux temperature between 60 and 140°

C.

31. The method of claim 27, wherein the alkyl sultone comprises 1,3-propane sultone or 1,4-butane sultone.

32. The method of claim 27, further comprising the alkylsulfonated chitosan having a known degree of substitution with the alkyl sultone.

33. A alkylsulfonated chitosan made by the process of:

adding a chitosan to an organic solvent to form a mixture;

heating the mixture to a reflux temperature;

reacting an alkyl sultone with the chitosan in the mixture to form a covalent bond between an alkyl sultone and an amino group of the chitosan resulting in an alkylsulfonated chitosan.

34. A formulation comprising an alkylsulfonated chitosan having a known size and degree of substitution and at least 50% of alkyl sultones attached to amino groups of the chitosan attached through a covalent bond.

35. The formulation of claim 34, further comprising the alkylsulfonated chitosan in an aqueous solution.

36. The formulation of claim 34, further comprising the alkylsulfonated chitosan in a film.

37. The formulation of claim 34, further comprising the alkylsulfonated chitosan in a powder form.

38. The formulation of claim 34, further comprising the formulation operable to promote wound healing in a wounded mammal.

39. The formulation of claim 34, further comprising the formulation operable to inhibit the growth of a micro-organism.

40. The formulation of claim 39, further comprising the micro-organism selected from the group consisting of:

streptomycin-resistant Staphylococcus aureus, E. coli CCRC 10675, Pseudomonas aeruginosa CCRC 12450 and Candida albicans CCRC 20511, and any combination thereof.

41. The formulation of claim 34, further comprising the formulation having no toxic effects in mammals.

42. The formulation of claim 34, further comprising the formulation having no inflammatory effects in mammals.

43. The formulation of claim 34, wherein the formulation is suitable for use in an application that uses chitosan.

44. The formulation of claim 34, wherein the formulation is suitable for use in a personal care product.

45. The formulation of claim 44, wherein the personal care product is selected from the group consisting of:

a hair care product, a nail polish, an oral care product, an odor control composition and a contact lens solution, and any combination thereof.

46. The formulation of claim 34, wherein the formulation is suitable for use in a food product.

47. The formulation of claim 46, wherein the food product is selected from the group consisting of:

a preserving agent, a film-like product, a health food, a dietary food, a food coating, a gelled emulsion, a weight-loss agent, a food additive and any combination thereof.

48. The formulation of claim 34, wherein the formulation is suitable for use in cleaning products.

49. The formulation of claim 34, wherein the formulation is suitable for use in an agricultural product.

50. The formulation of claim 49, wherein the agricultural product is selected from the group consisting of:

a feed additive, an animal food additive, a plant care product, a fertilizer, a grass cultivator, a disease inhibitor, an anti-fungal agent and any combination thereof.

51. The formulation of claim 34, wherein the formulation is suitable for use in a cosmetic.

52. The formulation of claim 51, wherein the cosmetic is selected from the group consisting of:

a beauty pack, an anti-aging cream, an acne cream, a make-up, a facial cleansing product and a maintenance product and any combination thereof.

53. The formulation of claim 51, wherein the cosmetic is selected from the group consisting of:

a gel, a cream, a grease, a spray, a bubble, a non-woven, a liquid, a powder and any combination thereof.

54. The formulation of claim 34, wherein the formulation is suitable for use as a medicine.

55. The formulation of claim 54, wherein the medicine is selected from the group consisting of:

an antibacterial agent, an anti-fungal agent, an anti-inflammatory agent, an anti-tumor agent, an anti-cholesterol agent, an anti-viral agent, a drug carrier, a vaccine, a microcapsule, a hydrogel, a fibrin adhesive, a fibrin sealant and any combination thereof.

56. The formulation of claim 34, wherein the formulation is suitable for use in medical devices.

57. The formulation of claim 56, wherein the medical device is a radiation therapy device or a leukocyte removal device.

58. The formulation of claim 34, wherein the formulation is suitable for use in weaves of nano-fibers.

59. The formulation of claim 34, wherein the formulation is suitable for use in a textile.

60. The formulation of claim 59, wherein the textile is selected from the group consisting of:

a natural fiber, a synthetic fiber and any combination thereof.

61. The formulation of claim 34, wherein the formulation is suitable for use in a water-treatment application.

62. The formulation of claim 61, wherein the water treatment application is selected from the group consisting of:

a heavy metal absorber, a lipid absorber, a protein absorber and any combination thereof.

63. The formulation of claim 34, wherein the formulation is suitable for use in a biochemistry product.

64. The formulation of claim 63, wherein the biochemistry product is selected from the groups consisting of:

an enzyme purifier, a enzyme holder, an exchangeable resin, a TLC material and any combination thereof.

65. An alkylsulfonated chitosan having a known size and degree of substitution and at least 50% of alkyl sultone attached to amino groups of the chitosan attached through a covalent bond.

66. A method of promoting wound healing in a wounded mammal comprising applying an alkylsulfonated chitosan to the wound.

67. The method of claim 66, wherein the wound is selected from the group consisting of:

an open wound, a bleeding wound, an open ulcer, a vascular graft, a vascular patch, a bleeding sutured area, a bleeding cardiac valve area and any combination thereof.

68. The method of claim 66, further comprising inhibiting fibroplasia.

69. The method of claim 66, further comprising promoting tissue regeneration in vascular grafts.

70. The method of claim 66, further comprising the alkylsulfonated chitosan in the form of a film.

71. The method of claim 66, further comprising the alkylsulfonated chitosan in a form selected from the group consisting of:

a fiber, a sponge, a gel, a cream, a grease, a spray, a bubble, a non-woven, a liquid, a powder and any combination thereof.

72. The method of claim 66, wherein the alkylsulfonated chitosan is applied for at least 14 days.

73. The method of claim 66, wherein the alkylsulfonated chitosan is applied for at least 21 days.