US20050283004A1 - Alkylsulfonated polyaminosaccharides - Google Patents

Alkylsulfonated polyaminosaccharides Download PDF

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US20050283004A1
US20050283004A1 US10/871,890 US87189004A US2005283004A1 US 20050283004 A1 US20050283004 A1 US 20050283004A1 US 87189004 A US87189004 A US 87189004A US 2005283004 A1 US2005283004 A1 US 2005283004A1
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chitosan
formulation
alkylsulfonated
polyaminosaccharide
sultone
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I-Chien Wei
Kung-Hsing Lee
Hsien-Ming Hung
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Hopax Chemicals Manufacturing Co Ltd
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Hopax Chemicals Manufacturing Co Ltd
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Assigned to HOPAX CHEMICALS MANUFACTURING CO., LTD. reassignment HOPAX CHEMICALS MANUFACTURING CO., LTD. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: HUNG, HSIEN-MING, LEE, KUNG-HSING, WEI, I-CHIEN
Priority to CA2510020A priority patent/CA2510020C/en
Priority to JP2005176255A priority patent/JP5415663B2/ja
Priority to TW094119987A priority patent/TWI305535B/zh
Priority to KR1020050052062A priority patent/KR101155884B1/ko
Priority to AU2005202652A priority patent/AU2005202652B2/en
Priority to CNB2005100781581A priority patent/CN100509859C/zh
Priority to EP05291299A priority patent/EP1607406A1/en
Priority to US11/157,132 priority patent/US8263763B2/en
Publication of US20050283004A1 publication Critical patent/US20050283004A1/en
Priority to JP2013000194A priority patent/JP5797673B2/ja
Abandoned legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/736—Chitin; Chitosan; Derivatives thereof
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02—Local antiseptics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/007—Preparations for dry skin
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
    • C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
    • C08B37/003—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/75—Anti-irritant

Definitions

  • the present invention relates to alkylsulfonated polyaminosaccharides, methods of making such molecules, and their uses, particularly in wound healing. Specific aspects of the invention relate to alkylsulfonated chitosan.
  • Polyaminosaccharides are of considerable interest in a number of fields ranging from medicine and agriculture to water treatment and cleaning products. However, the use of such molecules is somewhat limited by difficulties in dissolving them in water. Thus, various approaches have been used to increase solubility of polyaminosaccharides in water.
  • Chitosan is a polyaminosaccharide of particular interest in a number of applications. Like many polyaminosaccharides, chitosan may be readily harvested from naturally occurring materials. The primary source of chitosan is presently discarded shells of lobsters and crayfish or shrimp, although it may also be obtained from the shells of crabs and other crustaceans as well as from insect shells and fungi. Chitosan is normally non-toxic and is compatible with a variety of living systems, including human tissues. However, like many other polyaminosaccharides, chitosan exhibits only limited solubility in water.
  • Acids have been added to chitosan to increase its water solubility. It has also been sulfonated, which results in a molecule with a chemical structure similar to that of heparin, a powerful anticoagulant.
  • chlorosulfonic acid as a sulfonating agent in a low-polar solvent such as pyrimidine.
  • An organic base is then added as an acid receptor for the sulfonation reaction.
  • chlorosulfonic acid is not easy to use and it sulfonates not only at the amino group of the polyaminosaccharide, but also at other sites, such as the hydroxy groups. Additionally, the need to supply an acid receptor complicates the reaction. Overall, the reaction is difficult to carry out and often results in low yield of poorly characterized and unpredictable product.
  • alkyl sultones which are considerably easier to use than chlorosulfonic acid.
  • these methods add the alkyl sultones to chitosan in an aqueous acetic acid solution.
  • H 2 O reacts readily with alkyl sultones in the aqueous solution and hydrolyzes them, resulting in substantial loss of this reactant.
  • the hydrolyzed alkyl sultones form highly acidic alkylsulfonic acid, which then degrades the chitosan.
  • large amounts of alkyl sultone and chitosan are required for this method and yield is very poor, making the reaction economically unviable for many applications.
  • the length of the resulting alkylsulfonated chitosan varies widely, even when a uniform starting reagent is used.
  • the degree of substitution of the amino group with an alkyl sultone also varies widely and cannot be reliably predicted from the outset.
  • the present invention relates to methods of producing sulfonated polyaminosaccharides by reaction of the polyaminosaccharides with an alkyl sultone in an organic solvent.
  • the reaction occurs at reflux temperature.
  • the alkylsulfonated polyaminosaccharides may become less soluble or insoluble in the solution and may thus be readily recovered.
  • the resulting alkylsulfonated polyaminosaccharides may be of substantially the same length as prior to reaction. In addition, they may be sulfonated almost exclusively on the amino group and the degree of substitution may substantially correspond to that predicted at the outset of the reaction.
  • Alkylsulfonated polyaminosaccharides of the present invention may be non-toxic and biocompatible. They may be formed into films or non-woven structures, supplied in solution, or supplied and used in any other manner suitable for a given application. Specifically, some alkylsulfonated polyaminosaccharides of the present invention may be used for medical devices, personal care products, cosmetics, oral care products, odor control products, agricultural agents, water treatment, cleaning products, biochemistry products, contact lens solutions, and other medical products.
  • the alkylsulfonated polyaminosaccharides may include an alkylsulfonated chitosan.
  • This alkylsulfonated chitosan may be structurally similar to heparin.
  • Various forms may be used in a variety of manners, such as medical applications, including wound healing, disinfectants, water treatment, enzyme immobilization, and cosmetics.
  • FIG. 1 illustrates the reaction of chitosan and an alkyl sultone to produce alkylsulfonated chitosan, according to an embodiment of the present invention.
  • FIG. 4 is a graph showing the inflammatory effects of alkylsulfonated chitosan according to an embodiment of the present invention as measured by PGE 2 production by fibroblasts.
  • the concentration of PGE 2 was measured 24 hours after fibroblasts were treated with alkylsulfonated chitosan.
  • FIG. 5 illustrates the effects of (a) alginate (Kaltostat®), (b) unmodified chitosan sponge, (c) unmodified chitosan fibers, and (d) 80% substituted alkylsulfonated chitosan, according to an embodiment of the present invention, on wound healing in rats.
  • the FIGURE shows conditions of panniculus carnosis on the 21st day after operation.
  • FIG. 6 illustrates the cellular morphology of a clone L929 mouse fibroblasts negative control. Cells were grown on a Millipore AP250 1000 filter.
  • FIG. 7 illustrates the cellular morphology of clone L929 mouse fibroblasts grown around Kaltostat®.
  • FIG. 8 illustrates the cellular morphology of clone L929 mouse fibroblast grown around chitosan sponge.
  • FIG. 9 illustrates the cellular morphology of clone L929 mouse fibroblasts grown around chitosan fiber.
  • FIG. 10 illustrates the cellular morphology of clone L929 mouse fibroblasts grown around alkylsulfonated chitosan dressing according to an embodiment of the present invention.
  • FIG. 11 illustrates a histological analysis to analyze the cytotoxicity to cells grown around Kaltostat® (crystal violet stain).
  • FIG. 12 illustrates a histological analysis to analyze the cytotoxicity to cells grown around chitosan sponge (crystal violet stain).
  • FIG. 13 illustrates a histological analysis to analyze the cytotoxicity to cells grown around chitosan fiber (crystal violet stain).
  • FIG. 14 illustrates a histological analysis to analyze the cytotoxicity to cells grown around alkylsulfonated chitosan dressing according to an embodiment of the present invention (crystal violet stain).
  • the present invention includes alkylsulfonated polyaminosaccharides and methods for their creation and use. In selected embodiments, it relates to alkylsulfonated chitosan.
  • the polyaminosaccharide is placed in an organic solvent.
  • the polyaminosaccharide may be pre-processed to influence results of the reaction. For example, it may be deacetylated to allow access to the amino groups. It may also have protective groups to limit the degree of substitution, although in many embodiments this is not necessary. Reactive groups may be provided to facilitate other desirable reactions with the alkyl sultones.
  • the polyaminosaccharide may be of any size, but in specific embodiments it may have a molecular weight of between 300 and 200,000, more specifically between 3,000 and 140,000.
  • the organic solvent may be a highly polar solvent.
  • alcohol, ether, etheralcohol and mixtures thereof may be used as a solvent.
  • the solvent may have less than 10% water.
  • the alcohol may be methanol, ethanol, isopropanol or butanol or the ether may be methoxypropanol.
  • the mixture of polyaminosaccharide and solvent is next heated to reflux temperature (this may correspond with the boiling temperature of the mixture).
  • the reflux temperature may be between 50-150° C.
  • Alkyl sultones are added to the solution. They may be added gradually or all at once. The alkyl sultones normally react almost exclusively with the amino groups of the polyaminosaccharide, with little to no reaction with the hydroxy groups. Further the alkyl sultones normally primarily form covalent bonds with the amino groups of the completed alkyl sulfonated polyaminosuccharide, which are far more resistant to changes in the chemical environment than ionic bonds. Ionic bonds are the most common type of bond formed in many previous methods.
  • the present invention may result in at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% of sultone-amino group bonds being covalent bonds.
  • the alkyl sultones have a general formula of: where R 1 may be CH 2 , CH or C 2 H 4 ; R 2 may be CH 2 or CH; and R 3 may be H or CH 3 .
  • R 1 is CH 2 , R 2 is CH 2 , and R 3 is H; R 1 is CH, R 2 is CH, and R 3 is H; R 1 is CH 2 , R 2 is CH 2 , and R 3 is CH 3 ; R 1 is C 2 H 4 , R 2 is CH 2 , and R 3 is H.
  • the alkyl sultone may be 1,3-propane sultone, 1,3-propene sultone, 1,4-butane sultone, or 2,4-butane sultone.
  • alkyl sultone Only one type of alkyl sultone may be added, or a combination of two or more alkyl sultones may be used. Selection of the alkyl sultone and any combinations may be based on the desired properties and uses of the alkylsulfonated polyaminosaccharides to be produced. For example, selection of the alkyl sultone may be based on the need to perform further chemistry on the polyaminosaccharides, which may be facilitated by the presence of a specific alkyl group or influenced by steric effects of large alkyl groups.
  • the relative amounts of polyaminosaccharide and alkyl sultone used in the reaction may be selected to give a desired degree of substitution of the polyaminosaccharides.
  • the degree of substitution of alkylsulfonated polyaminosaccharides in selected embodiments of the present invention may be between 10% and 80%, between 5% and 60%, or between 30% and 40%.
  • the degree of substitution of alkylsulfonated polyaminosaccharides in selected embodiments of the present invention may also be at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95%.
  • the degree of substitution obtained using methods of the present invention tends to be consistent in many embodiments and is thus predictable through routine experimentation with various polyaminosaccharides and alkyl sultones.
  • the degree of substitution may be influenced by the amount and nature of the alkyl sultone added, although in many embodiments substantially all of the sultone reacts with the polyaminosaccharide.
  • the general length of the polyaminosaccharides also influences the degree of substitution, as longer molecules will have a larger number of sultones for a given degree of substitution when compared to a shorter molecule. Length of polyaminosaccharides may be readily determined based on various measurements known to the art, such as molecular weight. Reflux temperature, gradual versus immediate addition of the alkyl sultone, and reaction time may additionally influence the degree of substitution of the polyaminosaccharide.
  • the mole ratio of polyaminosaccharides to alkyl sultone may be between approximately 1:4 and 4:1. In more specific embodiments it may be between 1:2 and 2:1.
  • the alkylsulfonated polyaminosaccharide may be removed by filtration and dissolved in water or another solvent or crystallized.
  • the yield of this reaction is quite high, such as at least 50%, at least 80%, at least 90%, at least 95% or even at least 99%.
  • the size of the alkylsulfonated polyaminosaccharide may be known to a specificity normally accepted in the relevant field of use.
  • the known size will generally correspond with the size of the original polyaminosaccharide because the reaction does not cause substantial degradation of the polyaminosaccharide.
  • Alkylsulfonated polyaminosaccharides of the present invention may be used for a variety of purposes such as those described elsewhere in the present application. In order to facilitate these uses, they may be solubilized in water or an aqueous solvent to form solutions of different viscosities. They may also be used to form films or three-dimensional structures. Although a variety of forms may be sufficient for long-term storage, powdered or lyophilized alkylsulfonated polyaminosaccharides may be particularly well suited to avoid degradation and other problems associated with storage.
  • Chitosan is a long polymer of the general formula:
  • Chitosan of any type including the ⁇ , ⁇ , linear or branched types may be used in the present invention. It may be sulfonated on the amino groups. This renders the molecule more hydrophilic, produces cationic groups, and may stabilize the molecule.
  • chitosan may be reacted with an alkyl sultone as depicted in FIG. 1 .
  • amounts of sultone indicated in Table 1 may be used to obtain the indicated degree of substitution.
  • Table 1 shows that the degree of substitution of 1,3-propane sultone on chitosan is an approximately linear relationship to the amount of 1,3 propane sultone reactant.
  • the relationship between degree of substitution of the chitosan and the amount of sultone added may be approximately linear, particularly for degrees of substitution between 10% and 80%.
  • Alkylsulfonated chitosan produced by the above methodologies may be dissolved in water. This process is aided by the application of heat and stirring. The resulting solution is a weak acid with a transparent, light yellow color. The viscosity of the solution may be influenced by the amount of alkylsulfonated chitosan added. Alkylsulfonated chitosan may also be formed into a transparent, elastic film. In certain exemplary embodiments of the present invention, the elastic film may be produced by the dissolving the alkylsulfonated chitosan in a solvent, such as water, then evaporating the solvent. Other exemplary embodiments may use an oven to evaporate the solvent.
  • a solvent such as water
  • the solution of alkylsulfonated chitosan is placed in an oven for one day.
  • the thickness of this film may be varied, for example by controlling the concentration of the solution.
  • Alkylsulfonated chitosan films may be used, inter alia, in medicine, medical devices, cosmetics and food. Alkylsulfonated chitosan may also be formed into weaves of nano-fibers similar to those formed from chitosan in U.S. Pat. No. 6,638,918. It may then be put to similar uses. Additionally, microcapsules of alkylsulfonated chitosan may be formed and used in a manner similar to that described for chitin in U.S. Pat. No. 6,242,099.
  • Hydrogels may be formed as described using chitosan as the cationic polysaccharide in U.S. Pat. No. 5,858,392.
  • the alkylsulfonated chitosan of the present invention may be used to coat natural fibers as described in U.S. 2003/0134120.
  • Alkylsulfonated chitosan has been shown to inhibit streptomycin-resistant Staphylococcus aureus, E. coli CCRC 10675, Pseudomonas aeruginosa CCRC 12450 and Candida albicans CCRC 20511 and may be able to inhibit or kill various other harmful microorganisms.
  • the minimum inhibiting concentration of alkylsulfonated chitosan streptomycin-resistant Staphylococcus aureus is 0.38 mg/ml; for E.
  • alkylsulfonated chitosan may be used in place of chitosan in applications where anti-microbial effects are desirable to obtain a better product. Antimicrobial effects are largely independent of the size of the alkylsulfonated chitosan, the degree of substitution, or the sultone substituents.
  • alkylsulfonated chitosan may be useful in personal care products, food products, cleaning agents, agricultural agents, cosmetics, medicines and medical devices.
  • alkylsulfonated chitosan of the present invention may be used in place of chitosan in combination with elecampane as an anti-bacterial and anti-inflammatory agent as described in U.S. Pat. No. 6,521,628.
  • Fibers similar to anti-bacterial rayon fibers such as described in U.S. Pat. No. 6,497,927 may be made using alkylsulfonated chitosan of the present invention.
  • Cleaning products such as the mold and mildew remover of U.S. 2003/0176306 may be made with the alkylsulfonated chitosan of the present invention.
  • Alkylsulfonated chitosan of the present invention may also be used to enhance resistance of plants to disease, as described in U.S. Pat. No. 6,413,910. It may also be used to control plant diseases as described in U.S. Pat. No. 6,060,429 and U.S. Pat. No. 5,374,627.
  • alkylsulfonated chitosan of the present invention is normally an anti-microbial agent, some organisms, such as those described in U.S. Pat. No. 5,208,159, may actually grow well in it. It may also be used to encapsulate cells not harmed by the anti-microbial effects as is described for chitosan in U.S. Pat. No. 4,647,536.
  • alkylsulfonated chitosan exhibits little to no toxicity to larger organisms, such as mammals.
  • the acute oral toxicity (LD 50 ) amount for alkylsulfonated chitosan in rats is at least 5 g/kg, which is sufficient for it to be considered non-toxic.
  • alkylsulfonated chitosan does not appear to have significant effects on the weight of rats when ingested regularly. Therefore, alkylsulfonated chitosan may be used as an additive in foods or medicines.
  • alkylsulfonated chitosan of the present invention may be used in drug carriers or vaccines as described for unmodified chitosan in U.S. Pat. No.
  • alkylsulfonated chitosan of the present invention may be used in the place of chitosan in oral care and odor control compositions such as those described in U.S. 2003/0104020. It may also be used in place of native chitosan in food coatings, preservatives, or gelled emulsions as described in U.S. 2003/0203084, U.S. Pat. No. 6,200,619, U.S. Pat. No. 4,223,023 and U.S. Pat. No. 6,238,720, or it may be used as a drug, weight loss agent, or food additive as described in U.S. Pat. No. 6,495,142, U.S. Pat. No. 5,098,733 and U.S. Pat. No. 5,976,550.
  • alkylsulfonated chitosan does not irritate dermal tissue in rats or induce irregular or unusual growth. Thus it is appropriate to use in personal care products, cleaning products, cosmetics and medical devices.
  • alkylsulfonated chitosan of the present invention may be used with collagen to form beauty packs, as is described for chitosan in JP 6,048,917 and JP 5,345,712. It may be used in place of chitosan in an anti-aging cream as described in U.S. 2003/0104020 or in acne creams as described in U.S. Pat. No. 6,451,773. Use in place of chitosan in agents to aid in removal of adhesives from the epidermis as described in U.S. Pat. No. 6,461,635 is also possible.
  • alkylsulfonated chitosan of the present invention may be used in place of the cation residue of chitosan in a leukoreduction filter as described in U.S. Pat. No. 6,497,927.
  • Other filtration media may also be made from chitosan as described in U.S. Pat. No. 5,618,622.
  • Alkylsulfonated chitosan of the present invention may also be used in place of the water-soluble salt of chitosan employed in the hair care products and methods of U.S. Pat. No. 4,202,881 and U.S. Pat. No. 4,134,412. It may also be used in place of differently modified chitosan to form nail polish as described in U.S. Pat. No. 4,954,619.
  • Use of chitosans, which may be replaced with the alkylsulfonated chitosan of the present invention, in contact lens solutions is described in U.S. 2002/0177577.
  • Chitosan has been previously explored as a potential wound dressing or anticoagulant.
  • Alkylsulfonated chitosan produced using a method of the present invention ( FIG. 5D ) has been shown to be more effective in promoting wound healing than presently marketed alginate wound dressings (Kaltostat®, ConvaTec, Ltd., UK) ( FIG. 5A ), chitosan sponges ( FIG. 5B ) and chitosan fibers (Chinatex, Co. Ltd., Taiwan)( FIG. 5C ).
  • FIG. 5 clearly shows, the 80% sultone-substituted chitosan of the present invention produced markedly superior wound healing in rats.
  • alkylsulfonated chitosan may be used in place of chitosan or other modified chitosan in a number of wound healing applications.
  • U.S. Pat. No. 3,911,116, U.S. Pat. No. 4,532,134 and U.S. Pat. No. 3,914,413 all discuss the use of chitin or modified chitin in the promotion of wound healing.
  • the alkylsulfonated chitosan of the present application if used in the same manner as chitin in any of these three patents, would be expected to provide superior results.
  • the artificial skin described in U.S. Pat. No. 5,166,187 may be made with the alkylsulfonated chitosan of the present invention with expected improvements in the final product.
  • An example method of the present invention includes a method of wound healing in a wounded mammal comprising applying an alkylsufonated chitosan to the wound.
  • the wound may include open wounds, bleeding wounds, open ulcers, vascular grafts, vascular patches, bleeding saturated areas, bleeding cardiac valve areas, and any combination thereof.
  • the method may further include inhibiting fibroplasia and/or promoting tissue regeneration in vascular grafts.
  • Other embodiments of the present method have the alkylsulfonated chitosan in the form of a film, a fiber, a sponge, a bubble, a non-woven, a liquid, a powder and any combination thereof.
  • One embodiment of the present method applies the alkylsulfonated chitosan to the wound for at least 14 days.
  • Another embodiment applies the alkylsulfonated chitosan to the wound for at least 21 days.
  • alkylsulfonated chitosan of the present invention may be used in place of the chitosan of U.S. 2002/0189022 to treat textiles after washing.
  • alkylsulfonated chitosan may be used in place of chitosan to achieve superior results.
  • Chitosan with a molecular weight of between 10,000 and 200,000 was used.
  • Chitosan in the following examples generally includes poly(D-glucosamine) with about 75% to about 85% deacetylation.
  • 1,3-propane sultone or 1,4-butane sultone was used as the alkyl sultone.
  • the solvent for reaction was methanol, n-butanol or methoxypropanol.
  • Example 3 To prove the water-soluble sulfonated chitosan produced according to methods of Example 3 was sulfonated primarily with covalent bonds, the same process as described above in Example 2 was performed. After adding ammonia solution, the alkylfonated chitosan was precipitated, filtered, washed, and dried. Then the sulfur content was analyzed. Because the sulfur content was only reduced from 8% to 5%, the alkylsulfonated chitosan produced according to the method of Example 3 was sulfonated primarily with covalent bonds.
  • a 48-well plate was used for the present experiment although only the first 24 wells were used. All wells had a total volume of 1 ml.
  • the first well received only 0.5 ml of sterilized water and 0.5 ml of luria broth (LB).
  • the second well received 0.5 ml of alkylsulfonated chitosan sulfonated with 1,3-propane sultone was dissolved to 0.3% wt in 2 wt % acetic acid solution as well as 0.5 ml of bacterial or yeast culture (1 ml overnight bacterial or yeast solution+100 ml LB medium).
  • the third well received 0.5 ml of alkylsulfonated chitosan dissolved to 0.3% wt in 2 wt % acetic acid solution and 0.5 ml of sterilized water. After mixing 0.5 ml was transferred from the third well to the fourth well. 0.5 ml of sterilized water was then added to the fourth well and after mixing, 0.5 ml was transferred to the fifth well. Such serial dilutions were repeated through the twenty-fourth well. 0.5 ml of bacterial or yeast culture was added to the third to twenty-fourth wells.
  • a separate 48-well plate was used for each microorganism to be tested. Streptomycin-resistant Staphylococcus aureus, E. coli CCRC 10675, Pseudomonas aeruginosa CCRC 12450 and Candida albicans CCRC 20511 were all tested. Because microorganism growth renders the solution more opaque, spectroscopy may be used to detect microorganism growth. Scanning of the plate to detect the highest dilution/lowest concentration of alkylsulfonated chitosan that prevents further growth of the microorganism revealed the minimum inhibitory concentration (MIC) for each microorganism.
  • MIC minimum inhibitory concentration
  • Table 3 and FIG. 3 present the results of this test.
  • the level of irritation as determined chromatographically was highest after the first day for both test samples and the control rat, likely indicating the residual effects of shaving or irritation produced by petroleum jelly. However, statistical analysis indicated no obvious change over any of the days (p>0.05). Additionally, no skin irritation was observed in any of the rats on any day, so the assigned irritation value for visible observation was consistently 0.
  • Dermal cells were cultured in vitro and the concentration of prostaglandin (PGE 2 ), an indicator of inflammation, was measured through optical density at 405 nm after addition of alkylsulfonated chitosan 1,3-propane sultone. Ethanol, which does not inflame fibroblasts and cause release of PGE 2 was used as a negative control. Phorbol myristate acetate (PMA), a powerful inflammatory agent, was used as a positive control. 0.001, 0.002, 0.003 or 0.004 w/w % alkylsulfonated chitosan was added to the culture in the experiment.
  • PMA Phorbol myristate acetate
  • L929 mouse fibroblast cells were cultured to confluence in 6 cm plates. A sterile sample of one of four dressings was added to each plate. The dressings included a control millipore filler ( FIG. 6 ) and four experimental dressings including Kaltostat® ( FIG. 7 ), chitosan sponge ( FIG. 8 ), chitosan fiber ( FIG. 9 ), and 4 milligrams (mg) film of alkylsulfonated chitosan sulfonated with 1,3-propane sultone ( FIG. 10 ). Samples were added to the center of the dish, which was then incubated for one day. Cellular morphology was inspected microscopically. The morphology of cells around the four experimental dressings were the same with the negative control, which shows the dressings are all biocompatible.
  • Chitosan sponges used in these experiments were prepared by Chinatex by dissolving 5 w/w % chitosan in 2 Wt % acetic acid (aq) then placing the mixture in a 20 cm ⁇ 20 cm ⁇ 0.3 cm container. The mixture was freeze dried, then neutralized with 5% NaOH (aq ). The sponge was then washed in deionized water until neutral then freeze dried again.
  • Chitosan fibers were prepared by Chinatex by preparing the same initial mixture, then filtering it with a metal filter. After degassing, 5% NaOH (aq) was added and the mixture was wet-spun. The resulting fibers were washed with deionized water until neutral then dried.
  • Sprague-Dawley rats weighting around 250-300 g were anesthetized and their backs were shaved and disinfected.
  • a wound of approximately 3 cm ⁇ 3 cm was made using a surgical knife, removing the skin down to the panniculus carnosus.
  • a dressing made of Kaltostat®, a chitosan sponge, chitosan fiber, or alkylsulfonated chitosan film was then applied to the wound and covered with gauze.
  • a 6 cm ⁇ 7 cm piece of Tegaderm (3M, Minnesota) was then applied and secured with an elastic bandage wound around the rat.
  • the rats were kept in isolation and provided with food and water ad libidum. Healing of the wound was assessed after 3, 7, 14 and 21 days. The bandages were not replaced during this period, although they were temporarily removed for inspection.

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JP2005176255A JP5415663B2 (ja) 2004-06-18 2005-06-16 ヒドロカルビルスルトン化合物（ａ ｈｙｄｒｏｃａｒｂｙｌ ｓｕｌｔｏｎｅ ｃｏｍｐｏｕｎｄ）による化学修飾ポリアミノ糖
TW094119987A TWI305535B (en) 2004-06-18 2005-06-16 Chemically modified polyaminosaccharide by a hydrocarbyl sultone compound
KR1020050052062A KR101155884B1 (ko) 2004-06-18 2005-06-16 하이드로카르빌 설톤 화합물에 의해 화학적으로 변형된폴리아미노사카라이드
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CNB2005100781581A CN100509859C (zh) 2004-06-18 2005-06-17 通过烃基磺内酯化合物化学修饰的聚氨基糖
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Citations (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2755275A (en) * 1952-08-29 1956-07-17 Abbott Lab Process for sulfating chitin
US3911116A (en) * 1970-04-13 1975-10-07 Leslie L Balassa Process for promoting wound healing with chitin derivatives
US3914413A (en) * 1971-02-10 1975-10-21 Leslie L Balassa Process for facilitating wound healing with N-acetylated partially depolymerized chitin materials
US4134412A (en) * 1976-06-18 1979-01-16 Wella Aktiengesellschaft Hair setting lotion containing a chitosan derivative
US4202881A (en) * 1976-06-18 1980-05-13 Wella Ag Hair shampoo and conditioning lotion
US4223023A (en) * 1978-10-12 1980-09-16 Ivan Furda Nonabsorbable lipid binder
US4394373A (en) * 1981-04-06 1983-07-19 Malette William Graham Method of achieving hemostasis
US4532134A (en) * 1981-04-06 1985-07-30 Malette William Graham Method of achieving hemostasis, inhibiting fibroplasia, and promoting tissue regeneration in a tissue wound
US4647536A (en) * 1982-03-08 1987-03-03 Klaus Mosbach Method of encapsulating biomaterial in bead polymers
US4954619A (en) * 1987-07-18 1990-09-04 Wella Aktiengesellschaft O-benzyl-N-hydroxyalkyl derivatives of chitosan and nail polish containing the same
US5098733A (en) * 1988-10-15 1992-03-24 Suntory Limited Novel gel-like food articles and process for producing the same
US5129877A (en) * 1988-04-29 1992-07-14 University Of Georgia Research Foundation, Inc. Receptor-mediated delivery system
US5166187A (en) * 1987-06-15 1992-11-24 Centre National De La Recherche Biomaterials with a base of mixtures of collagen, chitosan and glycosaminoglycans, process for preparing them and their application in human medicine
US5208159A (en) * 1989-05-16 1993-05-04 Toda Biosystem Laboratory Antibacterial, anti-nematode and/or plant-cell activating composition, and chitinolytic microorganisms for producing the same
US5229504A (en) * 1990-09-07 1993-07-20 Dic-Hercules Chemicals, Inc. Process for preparing a sulfonated chitosan
US5336415A (en) * 1993-02-10 1994-08-09 Vanson L.P. Removing polyvalent metals from aqueous waste streams with chitosan and halogenating agents
US5374627A (en) * 1990-09-21 1994-12-20 Nakano Vinegar Co., Ltd. Methods for protecting vegetables, turfgrass, rice and fruit trees from fungi and bacteria
US5454907A (en) * 1990-12-25 1995-10-03 Japan Pmc Corporation Method of refining woodchips or beating wood pulp with a selectively sulfonated chitosan
US5543056A (en) * 1994-06-29 1996-08-06 Massachusetts Institute Of Technology Method of drinking water treatment with natural cationic polymers
US5629011A (en) * 1992-02-05 1997-05-13 Danbiosyst Uk Limited Composition for nasal administration
US5708152A (en) * 1992-03-27 1998-01-13 Ciba Specialty Chemicals Corporation N-substituted chitosan derivatives in a process for their preparation
US5762903A (en) * 1995-03-10 1998-06-09 Korea Atomic Energy Research Institute Radioactive chitosan complex for radiation therapy
US5858392A (en) * 1994-03-22 1999-01-12 Yissum Research Development Company Of The Hebrew University Of Jerusalem Supported polyionic hydrogels
US5902798A (en) * 1994-07-19 1999-05-11 Medicarb Ab Method of promoting dermal wound healing with chitosan and heparin or heparin sulfate
US5976550A (en) * 1998-11-20 1999-11-02 Engel; Peter H. Dietary food supplement
US6060429A (en) * 1994-07-25 2000-05-09 State of Israel--Ministry of Agriculture Composition and method for controlling plant diseases caused by fungi
US6200619B1 (en) * 1996-06-17 2001-03-13 Fuji Oil Co., Ltd. Preserving agent and preserving method
US6238720B1 (en) * 1997-02-28 2001-05-29 Nestec S.A. Gelled emulsion products containing chitosan
US6242099B1 (en) * 1996-11-21 2001-06-05 Merck S.A. Microcapsules made of chitin or of chitin derivatives containing a hydrophobic substance, in particular a sunscreen, and process for the preparation of such microcapsules
US6391398B1 (en) * 2000-04-18 2002-05-21 Bath & Body Works, Inc. Fragrant artificial flower apparatus
US6413910B1 (en) * 1997-05-15 2002-07-02 Iskra Industry Co., Ltd. Composition comprising chitosan for enhancing resistance to plant diseases
US6451773B1 (en) * 2000-03-31 2002-09-17 Cognis Corporation Chitosan formulation with azelaic acid and other actives for the treatment of acne
US6461635B2 (en) * 1999-10-25 2002-10-08 Access Business Group International Llc Method of forming a barrier on an epidermal surface
US20020177577A1 (en) * 2000-04-21 2002-11-28 Hung William M. Water soluble, randomly substituted partial N-partial O-acetylated chitosan, preserving compositions containing chitosan, and processes for making thereof
US6495142B2 (en) * 2000-09-13 2002-12-17 Kazuo Sakai Methods for treatment of impulse control disorders
US20020189022A1 (en) * 2001-06-05 2002-12-19 Chang Wen Chung Method for the treatment of textiles after washing
US6497927B1 (en) * 1997-06-04 2002-12-24 Korea Institute Of Science And Technology Method for preparing a filter for removal of leucoclytes coated with chitosan
US6497904B2 (en) * 1998-09-16 2002-12-24 Saira Sayed Singh Treatment of oncologic tumors with an injectable formulation of a golgi apparatus disturbing agent
US6503527B1 (en) * 1997-11-17 2003-01-07 Haemacure Corporation Fibrin sealants or adhesives comprising a hyaluronic acid derivative material
US6521268B2 (en) * 2001-02-08 2003-02-18 Jakwang Co., Ltd. Antibacterial and anti-inflammatory compositions with Inula helenium L. extract and water soluble chitosan
US6562802B2 (en) * 1996-12-16 2003-05-13 Noviscens Ab Medical composition and uses thereof
US20030104020A1 (en) * 2001-11-09 2003-06-05 Davison Gordon Robert Chitosan compositions
US20030114881A1 (en) * 2001-12-18 2003-06-19 Jan Stalemark Method and device for applying external pressure in combination with coagulant treatment of puncture wounds
US20030134120A1 (en) * 2001-12-24 2003-07-17 Ibeks Technologies Co., Ltd. Natural fiber coated with chitosan and a method for producing the same
US20030176306A1 (en) * 2000-10-06 2003-09-18 Mckechnie Malcolm Tom Cleaning compositions containing chitosan
US20030203084A1 (en) * 1999-07-13 2003-10-30 Unaxis Deutschland Gmbh. Coating composition for food products

Family Cites Families (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB838709A (en) * 1955-09-22 1960-06-22 Upjohn Co Improvements in or relating to aminoalcohol-n-sulphonic acid compounds
DE3422227A1 (de) 1984-02-29 1985-09-12 Jank, Wilhelm, 6794 Brücken Sicherungsklammer fuer die diebstahlssicherung von textilgegenstaenden u.dgl.
DE3432227A1 (de) * 1984-09-01 1986-03-13 Wella Ag, 6100 Darmstadt Sulfopropylderivate des chitins und chitosans, verfahren zu ihrer herstellung sowie ihre verwendung
JPH0667481B2 (ja) 1987-05-07 1994-08-31 富士紡績株式会社 陽イオン交換基を有する粒状多孔質キトサン誘導体の製造方法
JPH0648917B2 (ja) 1987-12-23 1994-06-22 日本精密機械工作株式会社 ブラシレスモータ
US5129887A (en) 1988-12-07 1992-07-14 Scimed Life Systems, Inc. Adjustable manifold for dilatation catheter
JPH02240101A (ja) * 1989-03-14 1990-09-25 Lion Corp 硫酸化キトサン誘導体及びその製造方法
IT1229167B (it) * 1989-04-10 1991-07-22 Texcontor Ets Complessi del ferro o di altri metalli con derivati solfonati del chitosano
JP2917257B2 (ja) 1990-08-22 1999-07-12 ダイハツ工業株式会社 四輪駆動車の駆動力制御装置
JPH04103534A (ja) * 1990-08-23 1992-04-06 Lion Corp ヘルペスウィルス性疾患処置剤
JPH05345712A (ja) 1991-04-19 1993-12-27 Noevir Co Ltd パック化粧料
JPH0648917A (ja) 1992-07-28 1994-02-22 Momoki Nakagawa 美容パック
KR0163098B1 (ko) * 1995-03-06 1998-11-16 정남환 수용성 술폰산화 키토산 및 그 제조방법
US5618622A (en) 1995-06-30 1997-04-08 Kimberly-Clark Corporation Surface-modified fibrous material as a filtration medium
GB9525083D0 (en) 1995-12-07 1996-02-07 Danbiosyst Uk Vaccine compositions
US6521628B1 (en) 1999-01-29 2003-02-18 Basf Aktiengesellschaft Fungicidal mixtures
JP3405942B2 (ja) * 1999-11-04 2003-05-12 花王株式会社 汚れ放出剤
US20050283004A1 (en) * 2004-06-18 2005-12-22 Hopax Chemicals Manufacturing Co., Ltd. Alkylsulfonated polyaminosaccharides

Patent Citations (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2755275A (en) * 1952-08-29 1956-07-17 Abbott Lab Process for sulfating chitin
US3911116A (en) * 1970-04-13 1975-10-07 Leslie L Balassa Process for promoting wound healing with chitin derivatives
US3914413A (en) * 1971-02-10 1975-10-21 Leslie L Balassa Process for facilitating wound healing with N-acetylated partially depolymerized chitin materials
US4134412A (en) * 1976-06-18 1979-01-16 Wella Aktiengesellschaft Hair setting lotion containing a chitosan derivative
US4202881A (en) * 1976-06-18 1980-05-13 Wella Ag Hair shampoo and conditioning lotion
US4223023A (en) * 1978-10-12 1980-09-16 Ivan Furda Nonabsorbable lipid binder
US4394373A (en) * 1981-04-06 1983-07-19 Malette William Graham Method of achieving hemostasis
US4532134A (en) * 1981-04-06 1985-07-30 Malette William Graham Method of achieving hemostasis, inhibiting fibroplasia, and promoting tissue regeneration in a tissue wound
US4647536A (en) * 1982-03-08 1987-03-03 Klaus Mosbach Method of encapsulating biomaterial in bead polymers
US5166187A (en) * 1987-06-15 1992-11-24 Centre National De La Recherche Biomaterials with a base of mixtures of collagen, chitosan and glycosaminoglycans, process for preparing them and their application in human medicine
US4954619A (en) * 1987-07-18 1990-09-04 Wella Aktiengesellschaft O-benzyl-N-hydroxyalkyl derivatives of chitosan and nail polish containing the same
US5129877A (en) * 1988-04-29 1992-07-14 University Of Georgia Research Foundation, Inc. Receptor-mediated delivery system
US5098733A (en) * 1988-10-15 1992-03-24 Suntory Limited Novel gel-like food articles and process for producing the same
US5208159A (en) * 1989-05-16 1993-05-04 Toda Biosystem Laboratory Antibacterial, anti-nematode and/or plant-cell activating composition, and chitinolytic microorganisms for producing the same
US5229504A (en) * 1990-09-07 1993-07-20 Dic-Hercules Chemicals, Inc. Process for preparing a sulfonated chitosan
US5374627A (en) * 1990-09-21 1994-12-20 Nakano Vinegar Co., Ltd. Methods for protecting vegetables, turfgrass, rice and fruit trees from fungi and bacteria
US5454907A (en) * 1990-12-25 1995-10-03 Japan Pmc Corporation Method of refining woodchips or beating wood pulp with a selectively sulfonated chitosan
US5629011A (en) * 1992-02-05 1997-05-13 Danbiosyst Uk Limited Composition for nasal administration
US5708152A (en) * 1992-03-27 1998-01-13 Ciba Specialty Chemicals Corporation N-substituted chitosan derivatives in a process for their preparation
US5336415A (en) * 1993-02-10 1994-08-09 Vanson L.P. Removing polyvalent metals from aqueous waste streams with chitosan and halogenating agents
US5858392A (en) * 1994-03-22 1999-01-12 Yissum Research Development Company Of The Hebrew University Of Jerusalem Supported polyionic hydrogels
US5543056A (en) * 1994-06-29 1996-08-06 Massachusetts Institute Of Technology Method of drinking water treatment with natural cationic polymers
US5902798A (en) * 1994-07-19 1999-05-11 Medicarb Ab Method of promoting dermal wound healing with chitosan and heparin or heparin sulfate
US6060429A (en) * 1994-07-25 2000-05-09 State of Israel--Ministry of Agriculture Composition and method for controlling plant diseases caused by fungi
US5762903A (en) * 1995-03-10 1998-06-09 Korea Atomic Energy Research Institute Radioactive chitosan complex for radiation therapy
US6200619B1 (en) * 1996-06-17 2001-03-13 Fuji Oil Co., Ltd. Preserving agent and preserving method
US6242099B1 (en) * 1996-11-21 2001-06-05 Merck S.A. Microcapsules made of chitin or of chitin derivatives containing a hydrophobic substance, in particular a sunscreen, and process for the preparation of such microcapsules
US6562802B2 (en) * 1996-12-16 2003-05-13 Noviscens Ab Medical composition and uses thereof
US6238720B1 (en) * 1997-02-28 2001-05-29 Nestec S.A. Gelled emulsion products containing chitosan
US6413910B1 (en) * 1997-05-15 2002-07-02 Iskra Industry Co., Ltd. Composition comprising chitosan for enhancing resistance to plant diseases
US6497927B1 (en) * 1997-06-04 2002-12-24 Korea Institute Of Science And Technology Method for preparing a filter for removal of leucoclytes coated with chitosan
US6503527B1 (en) * 1997-11-17 2003-01-07 Haemacure Corporation Fibrin sealants or adhesives comprising a hyaluronic acid derivative material
US6497904B2 (en) * 1998-09-16 2002-12-24 Saira Sayed Singh Treatment of oncologic tumors with an injectable formulation of a golgi apparatus disturbing agent
US5976550A (en) * 1998-11-20 1999-11-02 Engel; Peter H. Dietary food supplement
US20030203084A1 (en) * 1999-07-13 2003-10-30 Unaxis Deutschland Gmbh. Coating composition for food products
US6461635B2 (en) * 1999-10-25 2002-10-08 Access Business Group International Llc Method of forming a barrier on an epidermal surface
US6451773B1 (en) * 2000-03-31 2002-09-17 Cognis Corporation Chitosan formulation with azelaic acid and other actives for the treatment of acne
US6391398B1 (en) * 2000-04-18 2002-05-21 Bath & Body Works, Inc. Fragrant artificial flower apparatus
US20020177577A1 (en) * 2000-04-21 2002-11-28 Hung William M. Water soluble, randomly substituted partial N-partial O-acetylated chitosan, preserving compositions containing chitosan, and processes for making thereof
US6495142B2 (en) * 2000-09-13 2002-12-17 Kazuo Sakai Methods for treatment of impulse control disorders
US20030176306A1 (en) * 2000-10-06 2003-09-18 Mckechnie Malcolm Tom Cleaning compositions containing chitosan
US6521268B2 (en) * 2001-02-08 2003-02-18 Jakwang Co., Ltd. Antibacterial and anti-inflammatory compositions with Inula helenium L. extract and water soluble chitosan
US20020189022A1 (en) * 2001-06-05 2002-12-19 Chang Wen Chung Method for the treatment of textiles after washing
US20030104020A1 (en) * 2001-11-09 2003-06-05 Davison Gordon Robert Chitosan compositions
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JP2013100523A (ja) 2013-05-23
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TW200602355A (en) 2006-01-16
KR20060048401A (ko) 2006-05-18
AU2005202652B2 (en) 2011-11-17
JP5797673B2 (ja) 2015-10-21
CN1880343A (zh) 2006-12-20
US8263763B2 (en) 2012-09-11
CA2510020A1 (en) 2005-12-18
CN100509859C (zh) 2009-07-08
AU2005202652A1 (en) 2006-01-12
TWI305535B (en) 2009-01-21
CA2510020C (en) 2014-08-05
KR101155884B1 (ko) 2012-07-02
EP1607406A1 (en) 2005-12-21

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