CN104877042A - Preparation method of heparinoid - Google Patents
Preparation method of heparinoid Download PDFInfo
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- CN104877042A CN104877042A CN201510316035.0A CN201510316035A CN104877042A CN 104877042 A CN104877042 A CN 104877042A CN 201510316035 A CN201510316035 A CN 201510316035A CN 104877042 A CN104877042 A CN 104877042A
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- 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
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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
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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
- 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
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Abstract
The invention discloses a preparation method of heparinoid. The preparation method comprises the following steps : adopting chondroitin sulfate as a raw material, and treating to obtain heparinoid after sulfonation reaction. In the sulfonation reaction, the adopted solvent is formamide and the adopted sulfonating agent is free sulfur trioxide, fuming sulfuric acid or pyridine sulfur trioxide. The preparation method of heparinoid, disclosed by the invention, has the advantages that the synthesis process is simple, the production and the operation are easily controlled, no special requirement exists for production equipment, the molecular weight range of a product is stable, the physicochemical indexes of the product are controlled in the quality standard range, and simultaneously the product is high in yield and the method is suitable for large-scale industrial production.
Description
Technical field
The invention belongs to medical art, particularly relate to a kind of preparation method of biochemical drug heparitin.
Background technology
The material of heparitin and similar heparin is similar, the acidic mucopolysaccharide class material with anticoagulant active that have with heparin in chemical structure to a certain degree.There is antithrombus formation, anti-inflammatory, pain relieving, improve affected part blood circulation, absorb exudate, cure oedema and the effect such as edema, promotion tissue repair.Clinically be applicable to blood vessel embolism, varix, Superficial veins inflammation, lymphadenitis, mazoitis and softening scar.
Patent of invention document at present about heparitin has been reported, such as Japanese documentation (JP, S47-30167) vitriol oil is adopted to make sulphonating agent, react in pyridine with chondroitin sulfate under low temperature and prepare heparitin, Japanese documentation (JP, S59-133201) then adopt and make sulphonating agent with the nitration mixture of the vitriol oil and chlorsulfonic acid, chondroitin sulfate is carried out to the preparation method of structural modification.These methods all employ the vitriol oil excessive very greatly, and acid consumption is large, to production unit seriously corroded; liquid waste disposal difficulty, is unfavorable for environment protection, and production technique key point is difficult to control; the molecular weight ranges of products therefrom is unstable, and thus the performance index such as activity of product are also difficult to control.
It is sulphonating agent that European patent document (EP1634893) reports with chlorsulfonic acid, in formamide solvent, the method for heparitin is prepared in reaction, although heparitin major part physical and chemical index prepared by the method is easy to control, but " total nitrogen " index is restive in standard range, and chlorsulfonic acid is hazardous substance, meets water and namely explode, be unfavorable for transport and store, heat release in reaction process also produces a large amount of smog, there is very large potential safety hazard in production operation.In addition, when applicant repeats the method for above-mentioned document, the yield of product is lower, and production cost is higher, is thus not suitable for large-scale industrial production.
Summary of the invention
For the deficiencies in the prior art, the object of the invention is to improve defect that prior art exists and provide a kind of preparation method of heparitin, the method environmental protection, and product yield is high.
In order to realize object of the present invention, the main technical schemes provided is as follows, and concrete steps comprise:
A preparation method for heparitin, comprising: take chondroitin sulfate as raw material, obtains heparitin through sulfonation reaction aftertreatment; The solvent that described sulfonation reaction adopts is methane amide, and the sulphonating agent of employing is free sulphur trioxide (gaseous state or liquid state), oleum or pyridine. sulfur trioxide.
Described last handling process generally comprises removing impurity by means of precipitation, ion exchange resin desalination, concentrating under reduced pressure removes amine, hydrogen peroxide decolours and freezing dry process obtains heparitin.
Further, above-mentioned preparation method comprises the following steps:
(1) sulfonation reaction: chondroitin sulfate is dissolved in the methane amide of 5 ~ 10 times of volumes, adds sulphonating agent, at 0 ~ 80 DEG C of temperature, stirring reaction 3 ~ 12 hours, then adds organic solvent termination reaction, standing sedimentation, collecting precipitation thing;
(2) removing impurity by means of precipitation: the aqueous solution throw out that step (1) obtains being made into 10 ~ 20%W/V concentration, regulates pH value to 6 ~ 8 of the aqueous solution, and the organic solvent adding 2 ~ 3 times of volumes makes it precipitation; Throw out is made into the aqueous solution of 20 ~ 40%W/V concentration, the organic solvent adding 2 ~ 3 times of volumes makes it precipitation, collecting precipitation thing again;
(3) ion exchange resin desalination: the aqueous solution throw out that step (2) finally obtains being made into 10 ~ 30%W/V concentration, successively through storng-acid cation exchange resin, strongly basic anion exchange resin, carry out ion-exchange demineralization, collect the part that pH value is less than 4, then the pH value of collecting liquid is adjusted to 6.5 ~ 7.5;
(4) concentrating under reduced pressure is except amine: the collection liquid that step (3) obtains is heated to 35 ~ 45 DEG C, concentrating under reduced pressure boils off organic solvent, then adjust ph to 10.5 ~ 12, is heated to 45 ~ 55 DEG C, concentrating under reduced pressure remove portion water also takes residual organic solvent out of, obtains concentrated solution;
(5) hydrogen peroxide decolouring and lyophilize: the pH value of concentrated solution step (4) obtained is adjusted to 10 ~ 12, after hydrogen peroxide decolouring, pH value to 6 ~ 7 of regulation system, lyophilize obtains heparitin.
In the preparation method of above-mentioned heparitin, in the cartilaginous tissue of raw materials used chondroitin sulfate from pig, ox, product exists with the form of sodium salt.Buying producer comprises the company such as Jiaxing Hengjie Bio-Pharmaceutical Co., Ltd., ZHEJIANG AOXING BIOTECHNOLOGY CO., LTD, four tendril-leaved fritillary bulb Biology Pharmacy Co., Ltd, Shandong Yi Bao biological products company limited, Jinan Sheng Lin biotechnology company limited difficult to understand.
In above-mentioned steps (1), temperature of reaction is preferably 0 ~ 60 DEG C, and the reaction times is preferably 3 ~ 6 hours.As preferably, in step (1), when described sulphonating agent is pyridine. sulfur trioxide, sulfonation reaction temperature is 45 ~ 55 DEG C, and the reaction times is 3.5 ~ 4.5 hours.When described sulphonating agent is oleum, sulfonation reaction temperature is 20 ~ 30 DEG C, and the reaction times is 5 ~ 6 hours.When described sulphonating agent is for free sulphur trioxide (gaseous state or liquid state), sulfonation reaction temperature is 0 ~ 10 DEG C, and the reaction times is 2.5 ~ 3.5 hours.When adopting technique scheme, avoid using a large amount of sulfuric acid, while environmental protection pressure is little, improve the ultimate yield of product, relative to prior art, the yield of more than 10% can be improved.As preferred further, described sulphonating agent is pyridine. sulfur trioxide, and when adopting this technical scheme, yield is better, up to more than 95%, and simple to operate, convenient post-treatment.As preferably, in step (1), the organic solvent of termination reaction is at least one in methyl alcohol, ethanol, acetone.
In the present invention, adopt the removing impurity by means of precipitation of step (2), be mainly used in removing unnecessary sulfuric acid in the aqueous solution, remove residual methane amide further simultaneously.Organic solvent described in step (2) is at least one in methyl alcohol, ethanol, acetone.
As further preferably, in step (1) and step (2), described organic solvent is identical, is acetone.
In above-mentioned steps (3), described storng-acid cation exchange resin, strongly basic anion exchange resin are 2 ~ 6ml/g with the volume mass ratio of chondroitin sulfate.Described storng-acid cation exchange resin can select strongly-acid (polystyrene, acrylic acid series, phenolic aldehyde system, epoxy, vinylpyridine system, urea aldehyde system) Zeo-karb, and described strongly basic anion exchange resin can select strong basicity (polystyrene, acrylic acid series, phenolic aldehyde system, epoxy, vinylpyridine system, urea aldehyde system) anionite-exchange resin.
As preferably, described storng-acid cation exchange resin, strongly basic anion exchange resin are 3 ~ 4ml/g with the volume mass ratio of chondroitin sulfate.The preferred strongly acidic styrene type cation exchange resin of described storng-acid cation exchange resin, the preferred strong-basicity styrene series anion exchange resin of described strongly basic anion exchange resin
As preferably, in step (3), the pH value of collecting liquid is adjusted to 7 ± 0.2.This step mainly removes the salt be mingled with in product, reduces cl content.
As preferably, in step (4), concentrating under reduced pressure boils off organic solvent, then regulates pH to 11.5 ± 0.2 with alkali.In this step, time concentrated, be concentrated into 2/3 ~ 3/4 volume that condensate precursor is long-pending.This step mainly removes organic solvent.
As preferably, in step (5), the pH value of concentrated solution step (4) obtained is adjusted to 11.0 ± 0.5.
In the present invention, the alkali being used for regulating pH is 20 ~ 30% aqueous sodium hydroxide solutions.Acid can adopt sulfuric acid etc.
The preparation method of heparitin of the present invention, synthesis technique is simple, and production operation is easy to control, production unit is without particular requirement, molecular weight product range stabilises, physical and chemical index control within the scope of quality standard, and product yield is high simultaneously, are applicable to large-scale industrial production.
Embodiment
Further illustrate the present invention below in conjunction with specific embodiment how to realize, following examples contribute to understanding the present invention, but do not limit the present invention.
Embodiment 1:
(1) by 100g chondroitin sulfate (Jiaxing Hengjie Bio-Pharmaceutical Co., Ltd., EP7.0 standard) be dissolved in the methane amide of 1000ml, add 150g pyridine. sulfur trioxide solid, be heated to 50 DEG C, stirring reaction 4 hours, then 2000ml acetone termination reaction is added, standing sedimentation, collecting precipitation thing;
(2) above-mentioned throw out 800ml purified water being dissolved, is aqueous solution regulation system pH value to 7 ± 0.5 of the NaOH of 30% with mass percent concentration, and the acetone adding 2 times of volumes makes it precipitation; Throw out 400ml purified water dissolved, the acetone adding 2 times of volumes makes it precipitation, collecting precipitation thing again;
(3) above-mentioned throw out 800ml purified water is dissolved, successively through 400ml storng-acid cation exchange resin (Shanghai Kai Ping resin company limited, 001 × 7), 400ml strongly basic anion exchange resin (Shanghai Kai Ping resin company limited model:, model: 201 × 7), carry out ion-exchange demineralization, collecting the part that pH value is less than 4, is then that the pH value of collecting liquid is adjusted to 7 ± 0.2 by the aqueous solution of the NaOH of 30% with mass percent concentration;
(4) above-mentioned collection liquid is heated to 40 DEG C, concentrating under reduced pressure boils off residual acetone, then be pH value to 11.5 ± 0.2 of the aqueous solution adjustment remaining liq of the NaOH of 30% with mass percent concentration, be heated to 50 DEG C, be evaporated to about surplus 400ml concentrated solution;
(5) aqueous solution 20ml that mass percent concentration is the hydrogen peroxide of 30% is added in the concentrated solution obtained to step (4), NaOH with 30% adjusts system pH to 11.0 ± 0.5,30 DEG C are stirred decolouring 1 ~ 2 hour, system pH to 6.5 ± 0.5 is adjusted with sulfuric acid, lyophilize obtains heparitin 98g, calculate according to mass yield, total recovery is 98%.
Embodiment 2:
100g chondroitin sulfate is dissolved in the methane amide of 900ml, is slowly added dropwise to the oleum 160ml that mass percent concentration is 60%, temperature control 20 ~ 30 DEG C, stirring reaction 6 hours, then adds 1800ml acetone termination reaction, standing sedimentation, collecting precipitation thing;
Embodiment 1 is shown in aftertreatment, and last lyophilize obtains heparitin product 95g, and total recovery is 95%.
Embodiment 3:
100g chondroitin sulfate is dissolved in the methane amide of 950ml, under stirring, slowly passes into sulfur trioxide gas, temperature control 0 ~ 10 DEG C, insulation reaction 3 hours, then add 1900ml acetone termination reaction, standing sedimentation, collecting precipitation thing;
Embodiment 1 is shown in aftertreatment, and last lyophilize obtains heparitin product 95g, and total recovery is 95%.
The main physical and chemical index of the heparitin product that embodiment of the present invention 1-3 prepares is as follows:
Outward appearance: white or yellowish white powder
pH：6.0～7.5
Specific optical rotation :-11.7 ° ~-14.7 °
Weight loss on drying :≤6%
Residue on ignition: 38% ~ 48%
Electrophoresis: 1.07 ~ 1.16
Total nitrogen: 1.6% ~ 2.0%
Limiting viscosity: 0.09 ~ 0.18
Organosulfur acid group: 25.8% ~ 37.3%
Free sulphur :≤13%
D-Glucose aldehydic acid: 19% ~ 24%
Hyaluronidase: 14% ~ 29%
Total chlorine: < 0.178%
Comparative example 1:
Utilize the pyridine. sulfur trioxide that the chlorsulfonic acid with molar weight replaces in embodiment 1, carry out subsequent reactions according to identical step, last lyophilize obtains heparitin product 83g, and productive rate is 83% well below the yield of the embodiment of the present invention 1.
Comparative example 2
Utilize with the pyridine. sulfur trioxide in the sulphur trioxide replacement embodiment 1 of molar weight, isopyknic pyridine is utilized to replace methane amide as solvent, carry out subsequent reactions according to identical step, last lyophilize obtains heparitin product 73g, and productive rate is 73% well below the yield of the embodiment of the present invention 1.
Comparative example 3:
Omit the step (3) in embodiment 1, all the other steps are with embodiment 1, and last lyophilize obtains heparitin product 100g, but cl content is more than 0.178%, cannot meet the requirement of product physical and chemical index.
The above; be only the specific embodiment of the present invention, protection scope of the present invention is not limited thereto, and is anyly familiar with those skilled in the art in the technical scope that the present invention discloses; the change that can expect easily or replacement, all should be encompassed within protection scope of the present invention.Therefore, the protection domain that protection scope of the present invention should define with claim is as the criterion.
Claims (10)
1. a preparation method for heparitin, comprising: take chondroitin sulfate as raw material, obtain heparitin through sulfonation reaction aftertreatment; The solvent that described sulfonation reaction adopts is methane amide, and the sulphonating agent of employing is free sulphur trioxide, oleum or pyridine. sulfur trioxide.
2. the preparation method of heparitin according to claim 1, is characterized in that, specifically comprises the following steps:
(1) be dissolved in by chondroitin sulfate in the methane amide of 5 ~ 10 times of volumes, add sulphonating agent, at 0 ~ 80 DEG C of temperature, stirring reaction 3 ~ 12 hours, then adds organic solvent termination reaction, standing sedimentation, collecting precipitation thing;
(2) throw out that step (1) obtains is made into the aqueous solution of 10 ~ 20%W/V concentration, regulates pH value to 6 ~ 8 of the aqueous solution, add the organic solvent of 2 ~ 3 times of volumes, sediment separate out; Again throw out is made into the aqueous solution of 20 ~ 40%W/V concentration, adds the organic solvent of 2 ~ 3 times of volumes, collecting precipitation thing;
(3) throw out that step (2) finally obtains is made into the aqueous solution of 10 ~ 30%W/V concentration, successively through storng-acid cation exchange resin, strongly basic anion exchange resin, carry out ion-exchange demineralization, collect the part that pH value is less than 4, then the pH value of collecting liquid is adjusted to 6.5 ~ 7.5;
(4) the collection liquid that step (3) obtains is heated to 35 ~ 45 DEG C, concentrating under reduced pressure boils off organic solvent, then adjust ph to 10.5 ~ 12, is heated to 45 ~ 55 DEG C, concentrating under reduced pressure remove portion water also takes residual organic solvent out of, obtains concentrated solution;
(5) pH value of concentrated solution step (4) obtained is adjusted to 10 ~ 12, and after hydrogen peroxide decolouring, pH value to 6 ~ 7 of regulation system, lyophilize obtains heparitin.
3. the preparation method of heparitin according to claim 2, is characterized in that, in the cartilaginous tissue of raw materials used chondroitin sulfate from pig, ox, product exists with the form of sodium salt.
4. the preparation method of heparitin according to claim 2, is characterized in that, in step (1), temperature of reaction is 0 ~ 60 DEG C, and the reaction times is 3 ~ 6 hours.
5. the preparation method of heparitin according to claim 4, is characterized in that, when described sulphonating agent is pyridine. sulfur trioxide, sulfonation reaction temperature is 45 ~ 55 DEG C, and the reaction times is 3.5 ~ 4.5 hours; When described sulphonating agent is oleum, sulfonation reaction temperature is 20 ~ 30 DEG C, and the reaction times is 5 ~ 6 hours; When described sulphonating agent is for free sulphur trioxide, sulfonation reaction temperature is 0 ~ 10 DEG C, and the reaction times is 2.5 ~ 3.5 hours.
6. the preparation method of heparitin according to claim 5, is characterized in that, described sulphonating agent is pyridine. sulfur trioxide.
7. the preparation method of heparitin according to claim 2, is characterized in that, in step (1), the organic solvent of termination reaction is at least one in methyl alcohol, ethanol, acetone.
8. the preparation method of heparitin according to claim 2, is characterized in that, in step (2), the organic solvent of precipitation is at least one in methyl alcohol, ethanol, acetone.
9. the preparation method of heparitin according to claim 2, is characterized in that, described storng-acid cation exchange resin, strongly basic anion exchange resin are 2 ~ 6ml/g with the volume mass ratio of chondroitin sulfate.
10. the preparation method of heparitin according to claim 9, is characterized in that, described storng-acid cation exchange resin is strongly acidic styrene type cation exchange resin; Described strongly basic anion exchange resin is strong-basicity styrene series anion exchange resin.
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510316035.0A CN104877042B (en) | 2015-06-10 | 2015-06-10 | A kind of preparation method of heparan |
| DE112016001603.4T DE112016001603T5 (en) | 2015-06-10 | 2016-05-18 | Production process of heparinoid |
| PCT/CN2016/082482 WO2016197799A1 (en) | 2015-06-10 | 2016-05-18 | Method for preparing heparinoid |
| KR1020177032344A KR101966435B1 (en) | 2015-06-10 | 2016-05-18 | Process for the preparation of helianidides |
| JP2018507767A JP6486554B2 (en) | 2015-06-10 | 2016-05-18 | Method for producing heparinoid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510316035.0A CN104877042B (en) | 2015-06-10 | 2015-06-10 | A kind of preparation method of heparan |
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| Publication Number | Publication Date |
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| CN104877042A true CN104877042A (en) | 2015-09-02 |
| CN104877042B CN104877042B (en) | 2017-08-29 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201510316035.0A Active CN104877042B (en) | 2015-06-10 | 2015-06-10 | A kind of preparation method of heparan |
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| Country | Link |
|---|---|
| JP (1) | JP6486554B2 (en) |
| KR (1) | KR101966435B1 (en) |
| CN (1) | CN104877042B (en) |
| DE (1) | DE112016001603T5 (en) |
| WO (1) | WO2016197799A1 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016197799A1 (en) * | 2015-06-10 | 2016-12-15 | 浙江三门恒康制药有限公司 | Method for preparing heparinoid |
| CN107987184A (en) * | 2017-12-04 | 2018-05-04 | 唐财坤 | A kind of preparation method of heparan |
| CN111825777A (en) * | 2020-07-13 | 2020-10-27 | 山东众山生物科技有限公司 | Method for preparing heparinoids from chondroitin |
| CN112279936A (en) * | 2020-11-12 | 2021-01-29 | 上海辉文生物技术股份有限公司 | Preparation method of heparinoid |
| CN115210266A (en) * | 2020-03-04 | 2022-10-18 | 乐斯福公司 | Process for the direct sulphation of polysaccharides in ecologically acceptable solvents |
Citations (3)
| 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) |
| EP1634893A1 (en) * | 2004-09-13 | 2006-03-15 | Laboratori Derivati Organici S.P.A. | Process for the sulfation of chondroitin |
| CN101717455A (en) * | 2009-12-15 | 2010-06-02 | 武汉大学 | Method for preparing heparinoid polysaccharide |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0699485B2 (en) * | 1984-08-14 | 1994-12-07 | 生化学工業株式会社 | Method for producing synthetic chondroitin polysulfate |
| US6388060B1 (en) * | 1998-11-06 | 2002-05-14 | Vascular Therapeutics Inc. | Process for the sulfation of uronic acid-containing polysaccharides |
| CN1789287A (en) * | 2005-12-20 | 2006-06-21 | 山东大学 | Poly-sulfated chondroitin sulfate and preparation method thereof |
| GB201001203D0 (en) * | 2010-01-25 | 2010-03-10 | Anamar Medical Ab | Use of pharmaceutically active compounds |
| HUE030096T2 (en) * | 2011-05-20 | 2017-04-28 | Gnosis Spa | Shark-like chondroitin sulphate and process for the preparation thereof |
| CN104877042B (en) * | 2015-06-10 | 2017-08-29 | 浙江三门恒康制药有限公司 | A kind of preparation method of heparan |
-
2015
- 2015-06-10 CN CN201510316035.0A patent/CN104877042B/en active Active
-
2016
- 2016-05-18 DE DE112016001603.4T patent/DE112016001603T5/en not_active Ceased
- 2016-05-18 JP JP2018507767A patent/JP6486554B2/en active Active
- 2016-05-18 WO PCT/CN2016/082482 patent/WO2016197799A1/en active Application Filing
- 2016-05-18 KR KR1020177032344A patent/KR101966435B1/en active IP Right Grant
Patent Citations (3)
| 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) |
| EP1634893A1 (en) * | 2004-09-13 | 2006-03-15 | Laboratori Derivati Organici S.P.A. | Process for the sulfation of chondroitin |
| CN101717455A (en) * | 2009-12-15 | 2010-06-02 | 武汉大学 | Method for preparing heparinoid polysaccharide |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016197799A1 (en) * | 2015-06-10 | 2016-12-15 | 浙江三门恒康制药有限公司 | Method for preparing heparinoid |
| CN107987184A (en) * | 2017-12-04 | 2018-05-04 | 唐财坤 | A kind of preparation method of heparan |
| CN115210266A (en) * | 2020-03-04 | 2022-10-18 | 乐斯福公司 | Process for the direct sulphation of polysaccharides in ecologically acceptable solvents |
| CN111825777A (en) * | 2020-07-13 | 2020-10-27 | 山东众山生物科技有限公司 | Method for preparing heparinoids from chondroitin |
| CN111825777B (en) * | 2020-07-13 | 2022-05-27 | 山东众山生物科技有限公司 | Method for preparing heparinoids from chondroitin |
| CN112279936A (en) * | 2020-11-12 | 2021-01-29 | 上海辉文生物技术股份有限公司 | Preparation method of heparinoid |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104877042B (en) | 2017-08-29 |
| DE112016001603T5 (en) | 2018-01-04 |
| JP2018514641A (en) | 2018-06-07 |
| KR101966435B1 (en) | 2019-04-05 |
| JP6486554B2 (en) | 2019-03-20 |
| WO2016197799A1 (en) | 2016-12-15 |
| KR20170136584A (en) | 2017-12-11 |
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