Alkylsulfonated polyaminosaccharides

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.

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 R 1  is CH 2 , CH or C 2 H 4 ; R 2  is CH or CH 2 ; and R 3  is H or CH 3 .  
   
   
       10 . The method of  claim 9 , wherein R 1  is CH 2 , R 2  is CH 2 , and R 3  is H.  
   
   
       11 . The method of  claim 9 , wherein R 1  is CH, R 2  is CH, and R 3  is H.  
   
   
       12 . The method of  claim 9 , wherein R 1  is CH 2 , R 2  is CH 2 , and R 3  is CH 3 .  
   
   
       13 . The method of  claim 9 , wherein R 1  is C 2 H 4 , R 2  is CH 2 , and R 3  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.