WO2016197799A1 - 一种类肝素的制备方法 - Google Patents
一种类肝素的制备方法 Download PDFInfo
- Publication number
- WO2016197799A1 WO2016197799A1 PCT/CN2016/082482 CN2016082482W WO2016197799A1 WO 2016197799 A1 WO2016197799 A1 WO 2016197799A1 CN 2016082482 W CN2016082482 W CN 2016082482W WO 2016197799 A1 WO2016197799 A1 WO 2016197799A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- heparinoid
- preparing
- exchange resin
- organic solvent
- reaction
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 25
- 229920001499 Heparinoid Polymers 0.000 title claims abstract 14
- 239000002554 heparinoid Substances 0.000 title claims abstract 14
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 16
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229920001287 Chondroitin sulfate Polymers 0.000 claims abstract description 15
- 229940059329 chondroitin sulfate Drugs 0.000 claims abstract description 15
- 238000006277 sulfonation reaction Methods 0.000 claims abstract description 13
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 claims abstract description 10
- FBPINGSGHKXIQA-UHFFFAOYSA-N 2-amino-3-(2-carboxyethylsulfanyl)propanoic acid Chemical compound OC(=O)C(N)CSCCC(O)=O FBPINGSGHKXIQA-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 6
- HIFJUMGIHIZEPX-UHFFFAOYSA-N sulfuric acid;sulfur trioxide Chemical compound O=S(=O)=O.OS(O)(=O)=O HIFJUMGIHIZEPX-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000002994 raw material Substances 0.000 claims abstract description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 22
- 239000000047 product Substances 0.000 claims description 19
- 239000003960 organic solvent Substances 0.000 claims description 16
- 239000002244 precipitate Substances 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 14
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 12
- 230000002378 acidificating effect Effects 0.000 claims description 12
- 239000003957 anion exchange resin Substances 0.000 claims description 12
- 239000007864 aqueous solution Substances 0.000 claims description 12
- 239000003729 cation exchange resin Substances 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 11
- 239000007788 liquid Substances 0.000 claims description 10
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 230000035484 reaction time Effects 0.000 claims description 8
- 239000012141 concentrate Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 238000001556 precipitation Methods 0.000 claims description 4
- 239000013049 sediment Substances 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 238000005342 ion exchange Methods 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 241000283690 Bos taurus Species 0.000 claims description 2
- 241000282887 Suidae Species 0.000 claims description 2
- 210000000845 cartilage Anatomy 0.000 claims description 2
- 159000000000 sodium salts Chemical class 0.000 claims description 2
- 238000010612 desalination reaction Methods 0.000 claims 1
- 238000012805 post-processing Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 8
- 238000009776 industrial production Methods 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 9
- 229920000669 heparin Polymers 0.000 description 9
- 229960002897 heparin Drugs 0.000 description 9
- 239000000126 substance Substances 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 4
- 238000004108 freeze drying Methods 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 229960000074 biopharmaceutical Drugs 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 238000004042 decolorization Methods 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- KGIGUEBEKRSTEW-UHFFFAOYSA-N 2-vinylpyridine Chemical compound C=CC1=CC=CC=N1 KGIGUEBEKRSTEW-UHFFFAOYSA-N 0.000 description 2
- 239000004593 Epoxy Substances 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 229920001807 Urea-formaldehyde Polymers 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- 238000011033 desalting Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 239000003456 ion exchange resin Substances 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- ODGAOXROABLFNM-UHFFFAOYSA-N polynoxylin Chemical compound O=C.NC(N)=O ODGAOXROABLFNM-UHFFFAOYSA-N 0.000 description 2
- 229920002567 Chondroitin Polymers 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 206010046996 Varicose vein Diseases 0.000 description 1
- FWJVFCJSTCCCKQ-UHFFFAOYSA-N [Sb].N1=CC=CC=C1 Chemical group [Sb].N1=CC=CC=C1 FWJVFCJSTCCCKQ-UHFFFAOYSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- ADCOVFLJGNWWNZ-UHFFFAOYSA-N antimony trioxide Inorganic materials O=[Sb]O[Sb]=O ADCOVFLJGNWWNZ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229940023913 cation exchange resins Drugs 0.000 description 1
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 description 1
- 238000005202 decontamination Methods 0.000 description 1
- 230000003588 decontaminative effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000002242 deionisation method Methods 0.000 description 1
- 238000005115 demineralization Methods 0.000 description 1
- 230000002328 demineralizing effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- -1 heated to At 50 ° C Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 201000003265 lymphadenitis Diseases 0.000 description 1
- 208000004396 mastitis Diseases 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000014508 negative regulation of coagulation Effects 0.000 description 1
- 150000004028 organic sulfates Chemical class 0.000 description 1
- 208000001297 phlebitis Diseases 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 208000027185 varicose disease Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B45/00—Formation or introduction of functional groups containing sulfur
- C07B45/02—Formation or introduction of functional groups containing sulfur of sulfo or sulfonyldioxy groups
-
- 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
Definitions
- the invention belongs to the technical field of medicine, and in particular relates to a preparation method of a biochemical drug heparin.
- Heparin-like substances which are heparin-like substances, are acidic mucopolysaccharides which have a certain degree of chemical structure similar to heparin and have anticoagulant activity. It has antithrombotic, anti-inflammatory, analgesic, improve blood circulation in the affected area, absorb exudate, cure edema and edema, and promote tissue repair. Clinically applicable to vascular embolism, varicose veins, superficial phlebitis, lymphadenitis, mastitis and softening scars.
- JP Japanese Patent Literature
- JP uses concentrated sulfuric acid as a sulfonating agent to react with chondroitin sulfate in pyridine to prepare heparin
- This patent document uses a mixed acid of concentrated sulfuric acid and chlorosulfonic acid as a sulfonating agent to prepare a structural modification of chondroitin sulfate.
- the European patent document (EP1634893) reports a method for preparing heparin by reacting chlorosulfonic acid as a sulfonating agent in a formamide solvent, although most of the physical and chemical indexes of heparin prepared by the method are easy to control, but “total nitrogen” "The index is difficult to control within the standard range, and chlorosulfonic acid is a dangerous product. It explodes when exposed to water, which is not conducive to transportation and storage. During the reaction process, it generates heat and generates a large amount of smoke. There are great safety hazards in production operations. Further, the applicant repeats the method of the above document, the yield of the product is low, and the production cost is high, which is not suitable for large-scale industrial production.
- the object of the present invention is to improve the defects of the prior art and to provide a method for preparing heparin-like, which is environmentally friendly and has high product yield.
- a preparation method of heparin-like comprising: treating chondroitin by using sulfonation reaction as chondroitin sulfate; the solvent used in the sulfonation reaction is formamide, and the sulfonating agent used is free trioxide.
- Sulfur gaseous or liquid
- fuming sulfuric acid or pyridine trisulfide.
- the post-treatment process generally includes precipitation decontamination, desalting of ion exchange resin, concentration of amines under reduced pressure, decolorization of hydrogen peroxide, and freeze-drying to obtain heparan.
- the above preparation method includes the following steps:
- Precipitation removal The precipitate obtained in the step (1) is formulated into an aqueous solution of 10 to 20% W/V concentration, the pH of the aqueous solution is adjusted to 6 to 8, and 2 to 3 times the volume is added. The organic solvent is allowed to precipitate; the precipitate is further formulated into an aqueous solution having a concentration of 20 to 40% W/V, and a 2 to 3 volume amount of an organic solvent is added to precipitate, and the precipitate is collected;
- step (3) concentration under reduced pressure to remove the amine: the liquid obtained in step (3) is heated to 35 ⁇ 45 ° C, concentrated under reduced pressure to remove organic solvent, and then adjust the pH to 10.5 ⁇ 12, heated to 45 ⁇ At 55 ° C, concentrated to remove some water under reduced pressure and bring out residual organic solvent to obtain a concentrated liquid;
- step (4) hydrogen peroxide decolorization and freeze-drying: the pH of the concentrate obtained in step (4) is adjusted to 10 ⁇ 12, after decolorization by hydrogen peroxide, adjust the pH of the system to 6 ⁇ 7, freeze-drying Get heparin.
- the raw material chondroitin sulfate used is derived from the cartilage tissue of pigs and cattle, and the product exists in the form of a sodium salt.
- Purchasing manufacturers include Jiaxing Hengjie Bio-Pharmaceutical Co., Ltd., Zhejiang Aoxing Biotechnology Co., Ltd., Sichuan Beiao Bio-Pharmaceutical Co., Ltd., Shandong Yibao Biological Products Co., Ltd., Jinan Shenglin Bio-engineering Co., Ltd. and other companies.
- the reaction temperature is preferably 0 to 60 ° C, and the reaction time is preferably 3 to 6 hours.
- the sulfonating agent is pyridine antimony trioxide
- the sulfonation reaction temperature is 45 to 55. °C
- the reaction time is 3.5 ⁇ 4.5 hours.
- the sulfonating agent is fuming barium sulfate
- the sulfonation reaction temperature is 20 to 30 ° C
- the reaction time is 5 to 6 hours.
- the sulfonating agent is free sulfur trioxide (gaseous or liquid)
- the sulfonation reaction temperature is 0 to 10 ° C, and the reaction time is 2.5 to 3.5 hours.
- the sulfonating agent is pyridine sulfur trioxide, and the technical solution is used, the yield is better, up to 95% or more, and the operation is simple, and the post-treatment is convenient.
- the organic solvent that terminates the reaction is at least one of methanol, ethanol, and acetone.
- the precipitation removal by the step (2) is mainly used for removing excess sulfuric acid in the aqueous solution, and further removing the residual formamide.
- the organic solvent described in the step (2) is at least one of methanol, ethanol, and acetone.
- the organic solvent is the same, and both are acetone.
- the volume ratio of the strongly acidic cation exchange resin, the strongly basic anion exchange resin and the chondroitin sulfate is 2 to 6 ml/g.
- the strongly acidic cation exchange resin can be selected to be strongly acidic
- styrene-based, acrylic-based, phenolic-based, epoxy-based, vinylpyridine-based, or urea-formaldehyde-based cation exchange resins wherein the strongly basic anion exchange resin can be strongly alkaline (styrene-based, acrylic-based, phenolic-based, An epoxy-based, vinylpyridine-based, urea-formaldehyde-based anion exchange resin.
- the volume ratio of the strongly acidic cation exchange resin, the strongly basic anion exchange resin to the chondroitin sulfate is 3 to 4 ml/g.
- the strongly acidic cation exchange resin is preferably a strongly acidic styrene-based cation exchange resin
- the strongly basic anion exchange resin is preferably a strongly basic styrene-based anion exchange resin.
- step (3) the pH of the collected liquid is adjusted to 7 ⁇ 0.2.
- This step mainly removes impurities from the product and reduces the chlorine content.
- step (4) the organic solvent is distilled off under reduced pressure, and then the pH is adjusted to 11.5 ⁇ 0 with a base.
- the hydrazine is concentrated and concentrated to a volume of 2/3 to 3/4 of the volume before concentration. This step is mainly to remove organic solvents.
- the pH of the concentrate obtained in the step (4) is adjusted to 11.0 ⁇ 0.5.
- the base for adjusting the pH is a 20 to 30% aqueous sodium hydroxide solution.
- the acid may be sulfuric acid or the like.
- the preparation method of the heparin-like product of the invention has simple synthesis process, easy control of production operation, no special requirements for production equipment, stable molecular weight range, controlled physical and chemical indexes within the scope of quality standards, and high yield of the same product. Suitable for large-scale industrial production.
- Embodiment 1 is a diagrammatic representation of Embodiment 1:
- chondroitin sulfate was dissolved in 900 ml of formamide, and 160 ml of fuming sulfuric acid having a mass percentage of 60% was slowly added dropwise, and the temperature was controlled at 20 to 30 ° C. The reaction was stirred for 6 hours, and then the reaction was terminated by adding 1800 ml of acetone. Allow to settle and collect sediment;
- Example 1 For the post-treatment, see Example 1, and finally freeze-dried to obtain 95 g of the heparan-like product, with a total yield of 95%.
- Example 1 For the post-treatment, see Example 1, and finally freeze-dried to obtain 95 g of the heparan-like product, with a total yield of 95%.
- D-glucuronic acid 19 ⁇ 3 ⁇ 4 ⁇ 24 ⁇ 3 ⁇ 4
- Step (3) in Example 1 is omitted, and the remaining steps are the same as in Example 1. Finally, the heparin-producing product is 100 g, but the chlorine content exceeds 0.178%, which cannot meet the physical and chemical index requirements of the product.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Dermatology (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020177032344A KR101966435B1 (ko) | 2015-06-10 | 2016-05-18 | 헤파리노이드의 제조방법 |
| DE112016001603.4T DE112016001603T5 (de) | 2015-06-10 | 2016-05-18 | Herstellungsverfahren von Heparinoid |
| JP2018507767A JP6486554B2 (ja) | 2015-06-10 | 2016-05-18 | ヘパリノイドの製造方法 |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510316035.0A CN104877042B (zh) | 2015-06-10 | 2015-06-10 | 一种类肝素的制备方法 |
| CN201510316035.0 | 2015-06-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2016197799A1 true WO2016197799A1 (zh) | 2016-12-15 |
Family
ID=53944744
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2016/082482 WO2016197799A1 (zh) | 2015-06-10 | 2016-05-18 | 一种类肝素的制备方法 |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JP6486554B2 (de) |
| KR (1) | KR101966435B1 (de) |
| CN (1) | CN104877042B (de) |
| DE (1) | DE112016001603T5 (de) |
| WO (1) | WO2016197799A1 (de) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104877042B (zh) * | 2015-06-10 | 2017-08-29 | 浙江三门恒康制药有限公司 | 一种类肝素的制备方法 |
| CN107987184A (zh) * | 2017-12-04 | 2018-05-04 | 唐财坤 | 一种类肝素的制备方法 |
| IT202000004564A1 (it) * | 2020-03-04 | 2021-09-04 | Lesaffre & Cie | Processo per la solfatazione diretta di polisaccaridi in solvente ecologicamente accettabile |
| CN111825777B (zh) * | 2020-07-13 | 2022-05-27 | 山东众山生物科技有限公司 | 一种由软骨素制备类肝素的方法 |
| CN112279936B (zh) * | 2020-11-12 | 2023-06-30 | 上海辉文生物技术股份有限公司 | 一种类肝素的制备方法 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6147701A (ja) * | 1984-08-14 | 1986-03-08 | Seikagaku Kogyo Co Ltd | 合成コンドロイチン多硫酸の製造法 |
| EP1634893A1 (de) * | 2004-09-13 | 2006-03-15 | Laboratori Derivati Organici S.P.A. | Verfahren zur Sulfierung von Chondroitin |
| CN1789287A (zh) * | 2005-12-20 | 2006-06-21 | 山东大学 | 一种多硫酸化硫酸软骨素及其制备方法 |
| CN103635491A (zh) * | 2011-05-20 | 2014-03-12 | 灵知股份公司 | 类鲨鱼硫酸软骨素及其制备方法 |
| CN104877042A (zh) * | 2015-06-10 | 2015-09-02 | 浙江三门恒康制药有限公司 | 一种类肝素的制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB796737A (en) * | 1954-09-10 | 1958-06-18 | Hoffmann La Roche | A process for the production of glycan poly-(sulphuric acid esters) |
| US6388060B1 (en) * | 1998-11-06 | 2002-05-14 | Vascular Therapeutics Inc. | Process for the sulfation of uronic acid-containing polysaccharides |
| CN101717455B (zh) * | 2009-12-15 | 2011-08-24 | 武汉大学 | 一种类肝素多糖的制备方法 |
| GB201001203D0 (en) * | 2010-01-25 | 2010-03-10 | Anamar Medical Ab | Use of pharmaceutically active compounds |
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2015
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2016
- 2016-05-18 JP JP2018507767A patent/JP6486554B2/ja active Active
- 2016-05-18 DE DE112016001603.4T patent/DE112016001603T5/de not_active Ceased
- 2016-05-18 WO PCT/CN2016/082482 patent/WO2016197799A1/zh active Application Filing
- 2016-05-18 KR KR1020177032344A patent/KR101966435B1/ko active IP Right Grant
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| JPS6147701A (ja) * | 1984-08-14 | 1986-03-08 | Seikagaku Kogyo Co Ltd | 合成コンドロイチン多硫酸の製造法 |
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| CN1789287A (zh) * | 2005-12-20 | 2006-06-21 | 山东大学 | 一种多硫酸化硫酸软骨素及其制备方法 |
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| CN104877042A (zh) * | 2015-06-10 | 2015-09-02 | 浙江三门恒康制药有限公司 | 一种类肝素的制备方法 |
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Also Published As
| Publication number | Publication date |
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| KR20170136584A (ko) | 2017-12-11 |
| DE112016001603T5 (de) | 2018-01-04 |
| JP6486554B2 (ja) | 2019-03-20 |
| CN104877042A (zh) | 2015-09-02 |
| CN104877042B (zh) | 2017-08-29 |
| KR101966435B1 (ko) | 2019-04-05 |
| JP2018514641A (ja) | 2018-06-07 |
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