WO2008059869A1 - Procédé de dégradation d'un polysaccharide - Google Patents

Procédé de dégradation d'un polysaccharide Download PDF

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Publication number
WO2008059869A1
WO2008059869A1 PCT/JP2007/072085 JP2007072085W WO2008059869A1 WO 2008059869 A1 WO2008059869 A1 WO 2008059869A1 JP 2007072085 W JP2007072085 W JP 2007072085W WO 2008059869 A1 WO2008059869 A1 WO 2008059869A1
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Prior art keywords
polysaccharide
molecular weight
compound
heparin
light
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PCT/JP2007/072085
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English (en)
Japanese (ja)
Inventor
Toshihiko Toida
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National University Corporation Chiba University
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Priority to JP2008544170A priority Critical patent/JP5354578B2/ja
Publication of WO2008059869A1 publication Critical patent/WO2008059869A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/727—Heparin; Heparan
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728—Hyaluronic acid
    • 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
    • A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • 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
    • 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
    • C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
    • C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
    • C08B37/0069—Chondroitin-4-sulfate, i.e. chondroitin sulfate A; Dermatan sulfate, i.e. chondroitin sulfate B or beta-heparin; Chondroitin-6-sulfate, i.e. chondroitin sulfate C; Derivatives thereof
    • 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
    • C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
    • C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
    • C08B37/0072—Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
    • 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
    • C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
    • C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
    • C08B37/0075—Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/28—Treatment by wave energy or particle radiation
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
    • C08L5/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
    • C08L5/10—Heparin; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
    • C08J2305/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
    • C08J2305/10—Heparin; Derivatives thereof

Definitions

  • the present invention relates to a method for reducing the molecular weight of a polysaccharide.
  • Polysaccharides such as hyaluronic acid, heparin, and chondroitin sulfate have effects such as moisturizing, blood coagulation inhibition, cell growth control, and immune activity regulation. It has been.
  • heparin binds to antithrombin, which is a serine protease inhibitor, and exhibits anticoagulant activity, and is therefore widely used as an anticoagulant in clinical settings.
  • chondroitin sulfate and hyaluronic acid are widely used as health foods because they are expected to have an anti-inflammatory effect on osteoarthritis and an anti-aging effect on skin.
  • the polysaccharide is generally a polymer having a large molecular weight, and when used as a pharmaceutical or health food, it needs to be water-soluble in order to exhibit its pharmacological activity and physiological activity. Therefore, it is important to make a polysaccharide having a lower molecular weight. Furthermore, in the case of heline, it is important to reduce the molecular weight from the viewpoint of suppressing the onset of palin-induced thrombocytopenia (HIT) due to side effects that may be caused by being a polymer. It is also important to reduce the molecular weight of chondroitin sulfate in order to enhance the absorbability from the intestinal tract.
  • HIT palin-induced thrombocytopenia
  • Patent Documents 1 and 2 listed below describe techniques for reducing the molecular weight of heparin by using nitrous acid.
  • Patent Documents 3 and 4 listed below describe techniques for reducing the molecular weight of heparin using a divalent metal and hydrogen peroxide.
  • Patent Document 5 listed below describes a technique for reducing the molecular weight of heparin using the enzyme herintinase.
  • Patent Document 6 below describes a technique for reducing the molecular weight of sodium hyaluronate using a titanium dioxide catalyst by light irradiation of a high-pressure mercury lamp.
  • Non-patent document 1 below describes the base.
  • a technique for reducing the molecular weight of heparin using the beta elimination reaction used is described.
  • Non-Patent Document 2 describes a technique for reducing the molecular weight of heparin by a radical reaction using a peroxide.
  • Patent Document 1 International Publication WO 2006/011179
  • Patent Document 2 International Publication WO 1998/014481
  • Patent Document 3 International Publication WO 1982/003627
  • Patent Document 4 JP-A-11 130801
  • Patent Document 5 JP-A-10-219002
  • Patent Document 6 Japanese Unexamined Patent Publication No. 2000-296174
  • Non-Patent Document 2 Anal Biochem., (2005), 344 (2): 193-203
  • the Feton reaction (reaction between hydrogen peroxide and a metal ion such as the same ion or iron ion) generated by ultraviolet rays included in light irradiation from a high-pressure mercury lamp is used. It is a very violent method for decomposing macromolecules by generating hydroxy radicals. For this purpose, covalent bonds other than glycosidic bonds in polysaccharides are cleaved, decarboxylated, desulfated and deaminated. As a result, the resulting low molecular weight product has a structure different from that of the original hyaluronic acid. It is no longer a substance that can be called “hyaluronic acid oligosaccharide”.
  • the present invention has many functions while maintaining the action of the polysaccharide.
  • An object is to provide a novel method capable of reducing the molecular weight of saccharides.
  • the present invention relates to the following aspects as a means for solving the above-described problems.
  • a method of reducing the molecular weight of polysaccharides by irradiating them with visible light in the presence of titanium dioxide is a method of reducing the molecular weight of polysaccharides by irradiating them with visible light in the presence of titanium dioxide.
  • the polysaccharide is heparin
  • the polysaccharide is chondroitin sulfate
  • polysaccharide refers to a monosaccharide found in nature, that is, a polymer in which neutral, acidic and basic aldoses and ketoses are constituent sugars and these are polymerized by glycosidic bonds.
  • examples of this polysaccharide include, but are not limited to, chondroitin sulfate, heparin, hyaluronic acid and the like.
  • visible region light refers to light having a wavelength in the range of 350 nm to 750 nm. Such light in the visible region can be easily obtained by using any means known to those skilled in the art, for example, using a high-pressure mercury lamp as a light source, and cutting ultraviolet rays with a Neurex glass filter.
  • the polysaccharide preferably contains at least one of chondroitin sulfate, heparin, and hyaluronic acid, although not limited thereto.
  • the amount of energy of the irradiated light in the visible region is preferably 1MJ or more and 20MJ or less. If the polysaccharide is heparin, 5MJ It is preferable that it is 12 MJ or less.
  • titanium dioxide is preferably used in an amount in the range of 0.1 lg to 10 g with respect to the polysaccharide lg.
  • FIG. 1 is a diagram showing the results of performing HPLC on Compound 1.
  • FIG. 2 is an NMR spectrum of Compound 1 and heparin without molecular weight reduction.
  • FIG. 3 is a graph showing the results of measuring anticoagulant activity for compound 1.
  • FIG. 4 is a diagram showing the results of HPLC for compound 2.
  • FIG. 5 shows the results of measuring anticoagulant activity for compound 2.
  • FIG. 6 is a diagram showing the results of performing HPLC on compound 3.
  • FIG. 7 shows the results of measuring anticoagulant activity for compound 3.
  • FIG. 8 is a diagram showing the results of HPLC on compound 4.
  • FIG. 9 shows the results of measuring anticoagulant activity for compound 4.
  • FIG. 10 is a diagram showing the results of HPLC for compound 5.
  • FIG. 11 is a graph showing the results of measuring anticoagulant activity for compound 5.
  • FIG. 12 is a diagram showing the results of HPLC for compound 6.
  • FIG. 13 is an NMR spectrum of compound 6 and chondroitin sulfate without molecular weight reduction.
  • FIG. 14 shows the results of measuring T cell differentiation-inducing action for compound 6.
  • One feature of the low molecular weight polysaccharide according to this embodiment is that the polysaccharide is irradiated with light in the visible region in the presence of titanium dioxide.
  • the polysaccharides are limited as long as they are monosaccharides found in nature, that is, neutral, acidic, basic aldoses, and ketoses as constituent sugars, which are polymers polymerized by glycosidic bonds.
  • chondroitin sulfate, heparin, hyaluronic acid and the like can be mentioned.
  • the molecular weight of the polysaccharide before being reduced in molecular weight is not limited as long as it is derived from natural products, but it is preferably 5,000 or more and 1,000,000 or less, more preferably 10 , 000 to 200,000.
  • lower molecular weight in the present invention based on the type and molecular weight of the original polysaccharide, the purpose of lower molecular weight, and the like. For example, it means that the molecular weight decreases until the molecular weight is about 40 to 85% of the molecular weight of the original polysaccharide.
  • the polysaccharide in the present embodiment is preferably dissolved in a solvent from the viewpoint of the reaction efficiency and the recovery rate that can be used as they are.
  • the solvent is not limited as long as the polysaccharide can be dissolved, but water, dimethyl sulfoxide, dimethylformamide and the like are preferable from the viewpoint of safety and solubility.
  • the concentration of the polysaccharide dissolved in the solvent is not limited as long as the decomposition reaction can proceed, but it is preferably in the range of 0.1 mol / 1 to 10 mol / l, for example. More preferably, it is in the range of 0.5 mol / l or more and 5 mol / l or less.
  • titanium dioxide receives light in the visible region and acts as a catalyst.
  • the amount of titanium dioxide is not limited, but for example, the polysaccharide to be reduced in molecular weight lg On the other hand, it is preferably in the range of not less than 0.1 lg and not more than 10 g, more preferably not less than 0.5 g and not more than 2 g.
  • the light in the visible region used in the present embodiment is not limited as long as the degradation reaction of the polysaccharide proceeds, but the wavelength range is preferably 350 nm or more and 500 nm or less, for example, and more Preferably they are 360 nm or more and 400 nm or less.
  • the amount of light energy is not limited as long as the degradation reaction of the polysaccharide proceeds, but the effect of lowering the molecular weight can be sufficiently obtained, while the action as a polysaccharide is sufficiently maintained. From this viewpoint, it is preferably in the range of 1 MJ to 20 MJ, more preferably in the range of 5 MJ to 10 MJ.
  • the polysaccharide when it is heparin, it prevents side effects caused by being a polymer, while maintaining the anticoagulant activity, within the range of 5 MJ or more and 12 MJ or less. It is preferable that when the polysaccharide is chondroitin sulfate, it is preferable to be within the range of 1 MJ or more and 20 MJ or less from the viewpoint of maintaining the immunostimulatory effect while preventing side effects caused by being a polymer. In the case where the polysaccharide is hyaluronic acid, it is preferable that it is in the range of 1 MJ or more and 20 MJ or less from the viewpoint of maintaining the water retention action while preventing side effects caused by being a polymer.
  • the molecular weight reduction according to this embodiment is not limited, but is weakly acidic (pH 4 to
  • reaction is carried out in an atmosphere of 7) to weakly alkaline (pH 7 to 10), and more preferably pH 7.
  • the method according to this embodiment does not use light harmful to the human body such as gamma rays and ultraviolet rays by irradiating light in the visible region, and is approved as a highly safe food additive. Because titanium dioxide (TiO), which is widely used, is used as a photocatalyst,
  • the reaction can be performed under mild conditions, for example, room temperature and neutral conditions. Furthermore, in order to irradiate light in the visible region, low molecular weight generation occurs under mild conditions. For this reason, the generation of unsaturated bonds in the structure of the low molecular weight polysaccharides causes cleavage other than glycosidic bonds. Is extremely rare. In addition, the structure of the sugar chain and the elimination of the sulfate group hardly occur, and the original effects of the polysaccharide can be kept high. In other words, the problems such as the introduction of unsaturated bonds and the decrease in activity due to the structural change of the sugar chain that occur in the conventional method can be minimized.
  • the structure and action of polysaccharides' The ability to provide a method for safely reducing the molecular weight of polysaccharides while maintaining its effects.
  • heparin having an average molecular weight of 20,000 manufactured by Celsus, Inc., Onio, USA
  • lg was dissolved in 20 ml of water (solvent) to obtain a sample solution.
  • titanium dioxide manufactured by the Japanese Pharmacopoeia “Exclusively manufactured”, Wako Co., Ltd.
  • lg was added and irradiated with light having a wavelength of 370 nm and intensity of 500 W for 180 minutes.
  • the sample solution after irradiation was subjected to removal of titanium dioxide by centrifugation and lyophilization to obtain white compound 1.
  • the light in the visible region used in the examples of the present invention is obtained by using a high-pressure mercury lamp manufactured by Senkou Kogyo Co., Ltd. (Osaka, Japan) and cutting ultraviolet rays with a glass filter manufactured by Pyrex.
  • anti-coagulant activity was measured for Compound 1 obtained above.
  • the anticoagulant activity was measured using human serum with chromozyme T as a chromogenic substrate.
  • Figure 3 shows the result.
  • the value of the anticoagulant activity was 162 USP units / mg, confirming that heparin's original anticoagulant action was not significantly reduced.
  • This compound has almost the same force S as compound 1, and the irradiation time of light in the visible region is different. That is, Compound 1 was irradiated with light having a wavelength of 370 nm and an intensity of 500 W for 180 minutes, whereas Compound 2 was different only in that it was irradiated for 60 minutes. As a result, white compound 2 could be obtained in this example.
  • the value of anticoagulant activity was 17 1 USP units / mg, and the original anticoagulant effect of henoline was not significantly reduced. Was confirmed.
  • This compound has almost the same force S as compound 1, and the irradiation time of light in the visible region is different. Immediately That is, Compound 1 was irradiated with light having a wavelength of 370 nm and intensity of 500 W for 180 minutes, whereas Compound 3 was different only in that it was irradiated for 120 minutes. As a result, white compound 3 could be obtained in this example.
  • the value of anticoagulant activity is 16 as a result.
  • the amount was 8 USP units / mg, and it was confirmed that the anticoagulant effect inherent in henoline was not greatly reduced.
  • This compound has almost the same force S as compound 1, and the irradiation time of light in the visible region is different. That is, Compound 1 was irradiated with light having a wavelength of 370 nm and an intensity of 500 W for 180 minutes, whereas Compound 4 was different only in that it was irradiated for 240 minutes. As a result, white compound 4 could be obtained in this example.
  • the value of anticoagulant activity was 150 USP units / mg, and the original anticoagulant effect of henoline was not greatly reduced. Was confirmed.
  • This compound has almost the same force S as compound 1, and the irradiation time of light in the visible region is different. That is, Compound 1 was irradiated with light having a wavelength of 370 nm and intensity of 500 W for 180 minutes, whereas Compound 5 was different only in that it was irradiated for 360 minutes. As a result, white compound 5 could be obtained in this example.
  • the value of anticoagulant activity is 14 as a result.
  • chondroitin sulfate (derived from shark cartilage, manufactured by Seikagaku Corporation, Tokyo) lg having an average molecular weight of 50,000 was dissolved in 20 ml of water (solvent) to obtain a sample solution.
  • titanium dioxide lg was added and irradiated with light having a wavelength of 370 nm and an intensity of 500 W for 360 minutes.
  • the sample solution after irradiation was subjected to removal of titanium dioxide by centrifugation and lyophilization to obtain white compound 6.
  • the compound 6 obtained above was measured for the mouse thymus-derived T cell differentiation-inducing action exhibited by chondroitin sulfate.
  • Measurement of mouse thymus-derived T cell differentiation-inducing activity was carried out using 10-week-old female Balb / c mice that were intravenously injected with adjuvant and ovalbumin twice every two weeks to activate spleen cells.
  • chondroitin sulfate or Compound 6 was added to the spleen cell culture medium.
  • Investigate the activity of inducing type 1 and type 2 helper T cells by quantifying the amount of site force-ins released into the medium after culturing for 1 week using a measurement kit did. The results are shown in FIG. As a result, it was confirmed that the action of controlling chondroitin sulfate original T cell differentiation was greatly reduced.
  • the method of the present invention can be applied to products containing polysaccharides such as pharmaceuticals, cosmetics, health foods, and food additives, and has industrial applicability in related fields.

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Abstract

L'invention concerne un procédé selon lequel un polysaccharide peut être dégradé tout en conservant l'effet du polysaccharide, ainsi qu'un polysaccharide dégradé. Le procédé selon l'invention de dégradation d'un polysaccharide comprend l'irradiation du polysaccharide avec une lumière dans la plage visible en présence de dioxyde de titane. Selon ce procédé, il est préférable que le polysaccharide contienne au moins un élément parmi le sulfate de chondroitine, l'héparine et l'acide hyaluronique. Il est également préférable que l'énergie de la lumière dans la plage visible pour l'irradiation soit supérieure ou égale à 1 MJ, mais inférieure ou égale à 20 MJ. Il est également préférable que le dioxyde de titane soit utilisé en une quantité supérieure ou égale à 0,1 g, mais inférieure ou égale à 10 g par gramme de polysaccharide tel que décrit précédemment.
PCT/JP2007/072085 2006-11-16 2007-11-14 Procédé de dégradation d'un polysaccharide WO2008059869A1 (fr)

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009297007A (ja) * 2008-06-16 2009-12-24 Makoto Yafuji 低分子コンドロイチン硫酸の製造方法
JP2010077256A (ja) * 2008-09-25 2010-04-08 Tottori Univ コンドロイチン硫酸の低分子化物の製造方法
JP2013199639A (ja) * 2012-02-21 2013-10-03 Hokkaido Research Organization コンドロイチン硫酸オリゴ糖を製造する方法
JP2015117198A (ja) * 2013-12-18 2015-06-25 日本薬品株式会社 コンドロイチン硫酸オリゴ糖を含む免疫賦活剤及びその製造方法
JP2015529679A (ja) * 2012-09-14 2015-10-08 イーエルシー マネージメント エルエルシー ケラチン表面の細胞での選択的分解代謝を改善するための方法および組成物
JP2016164179A (ja) * 2016-04-11 2016-09-08 日本薬品株式会社 コンドロイチン硫酸オリゴ糖を含む免疫賦活剤及びその製造方法
US10383815B2 (en) 2012-09-14 2019-08-20 Elc Management Llc Method and compositions for improving selective catabolysis in cells of keratin surfaces
CN115583998A (zh) * 2022-09-23 2023-01-10 江苏蓝果临床营养科技有限公司 一种低分子量硫酸软骨素-铁的制备方法

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JP2009297007A (ja) * 2008-06-16 2009-12-24 Makoto Yafuji 低分子コンドロイチン硫酸の製造方法
JP2010077256A (ja) * 2008-09-25 2010-04-08 Tottori Univ コンドロイチン硫酸の低分子化物の製造方法
JP2013199639A (ja) * 2012-02-21 2013-10-03 Hokkaido Research Organization コンドロイチン硫酸オリゴ糖を製造する方法
JP2015529679A (ja) * 2012-09-14 2015-10-08 イーエルシー マネージメント エルエルシー ケラチン表面の細胞での選択的分解代謝を改善するための方法および組成物
US10383815B2 (en) 2012-09-14 2019-08-20 Elc Management Llc Method and compositions for improving selective catabolysis in cells of keratin surfaces
JP2015117198A (ja) * 2013-12-18 2015-06-25 日本薬品株式会社 コンドロイチン硫酸オリゴ糖を含む免疫賦活剤及びその製造方法
JP2016164179A (ja) * 2016-04-11 2016-09-08 日本薬品株式会社 コンドロイチン硫酸オリゴ糖を含む免疫賦活剤及びその製造方法
CN115583998A (zh) * 2022-09-23 2023-01-10 江苏蓝果临床营养科技有限公司 一种低分子量硫酸软骨素-铁的制备方法
WO2024060946A1 (fr) * 2022-09-23 2024-03-28 江苏蓝果临床营养科技有限公司 Procédé de préparation de sulfate de chondroïtine-fer de faible poids moléculaire

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