CN106916235A - A kind of high efficiency extraction technique of liquaemin - Google Patents
A kind of high efficiency extraction technique of liquaemin Download PDFInfo
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- CN106916235A CN106916235A CN201710161939.XA CN201710161939A CN106916235A CN 106916235 A CN106916235 A CN 106916235A CN 201710161939 A CN201710161939 A CN 201710161939A CN 106916235 A CN106916235 A CN 106916235A
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- high efficiency
- liquaemin
- extraction technique
- efficiency extraction
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- 229920000669 heparin Polymers 0.000 title claims abstract description 36
- 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 title claims abstract description 32
- 238000000034 method Methods 0.000 title claims abstract description 24
- 238000000605 extraction Methods 0.000 title claims abstract description 18
- 239000007788 liquid Substances 0.000 claims abstract description 23
- 239000006025 fining agent Substances 0.000 claims abstract description 22
- 210000000813 small intestine Anatomy 0.000 claims abstract description 20
- 238000002156 mixing Methods 0.000 claims abstract description 19
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims abstract description 14
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims abstract description 14
- 210000004400 mucous membrane Anatomy 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 235000021314 Palmitic acid Nutrition 0.000 claims abstract description 7
- 229940075507 glyceryl monostearate Drugs 0.000 claims abstract description 7
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims abstract description 7
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000000926 separation method Methods 0.000 claims abstract description 6
- 238000010521 absorption reaction Methods 0.000 claims abstract description 5
- 238000001035 drying Methods 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 239000011347 resin Substances 0.000 claims description 11
- 229920005989 resin Polymers 0.000 claims description 11
- 239000011780 sodium chloride Substances 0.000 claims description 11
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 7
- 239000002002 slurry Substances 0.000 claims description 7
- 230000003647 oxidation Effects 0.000 claims description 5
- 238000007254 oxidation reaction Methods 0.000 claims description 5
- 108091005804 Peptidases Proteins 0.000 claims description 4
- 239000004365 Protease Substances 0.000 claims description 4
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 4
- 239000003463 adsorbent Substances 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 4
- 230000001186 cumulative effect Effects 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 239000012467 final product Substances 0.000 claims description 4
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 claims description 4
- 229960001008 heparin sodium Drugs 0.000 claims description 4
- 239000000155 melt Substances 0.000 claims description 4
- 238000000108 ultra-filtration Methods 0.000 claims description 4
- 230000033228 biological regulation Effects 0.000 claims description 3
- 239000000356 contaminant Substances 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 4
- 239000002699 waste material Substances 0.000 abstract description 4
- 238000003912 environmental pollution Methods 0.000 abstract description 2
- 238000001556 precipitation Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 14
- 239000003814 drug Substances 0.000 description 8
- 239000012535 impurity Substances 0.000 description 8
- 229960002897 heparin Drugs 0.000 description 5
- 239000000284 extract Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000012266 salt solution Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000001631 haemodialysis Methods 0.000 description 2
- 230000000322 hemodialysis Effects 0.000 description 2
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- -1 with high income 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
- 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
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0003—General processes for their isolation or fractionation, e.g. purification or extraction from biomass
Abstract
The present invention relates to a kind of high efficiency extraction technique of liquaemin, raw material is mucous membrane of small intestine, by enzymolysis, the preparation of fining agent, absorption, standing separation, precipitation drying, liquaemin is obtained.Present invention employs new adsorbing contaminant method, used as fining agent using glyceryl monostearate and palmitic acid mixing, with very good effect.The present invention has the advantages that high income, waste liquid are few, environmental pollution is small, waste liquid is easily processed, and is adapted to industrialized production, with social and economic benefit.
Description
Technical field
The present invention relates to a kind of high efficiency extraction technique of liquaemin, belong to the production technical field of liquaemin.
Background technology
Liquaemin is the anticoagulation medicine of most effective in the world and quantity maximum at present, is mainly used in cardiovascular and cerebrovascular
Disease and hemodialysis, wherein being the only effective specific medicament in hemodialysis.Clinical practice and research are aobvious
Show, liquaemin in addition to blood coagulation resisting function, also with other multiple biological activities and clinical application, including effect for reducing blood fat,
The effect such as film smooth muscle cell (SMC) hyperplasia, promotion fibrinolysis in anti-.Additionally, LMWHs is by heparin raw material
The medicine of the major class antithrombotic that medicine is further processed into as raw material, with more extensive clinical medicine purposes, as controlling
Treat the choice drug of the disease such as Acute Venous thrombus and acute coronary artery syndrome (angina pectoris, miocardial infarction).Heparin is in the world
The most complicated compound of hitherto known molecular structure, cannot be synthesized by artificial chemistry in a short time, and pig is only derived from present
The liquaemin of mucous membrane of small intestine can be used in clinical treatment.
The raw material of heparin bulk drug is heparin crude product, and its extraction can only be derived from the mucous membrane of small intestine of healthy live pig, due to containing
A large amount of impurity protein, contaminant nucleic acid and contaminating microorganisms etc., need to orient and obtain day by physics and chemical extraction separation process
The complete heparin of right building stone, so as to be made liquaemin bulk drug.
The method of the invention description traditional mode of production liquaemin of CN101805764A typically has two kinds:Salt solution is extracted, enzymolysis
Method is extracted and digested and extracted with salt solution.Salt solution extract shortcoming be:Decompose incomplete, residual quantity is than larger.Enzymatic isolation method
Shortcoming is:Impurity after decomposition is relatively more, and purity is low, and many impurity also can cause resin abortive response with resin-bonded, while
Also increase consumption, reduce resin service life.
The content of the invention
The present invention is in view of the shortcomings of the prior art, there is provided a kind of process is simple, the new method of high income, the method have
Beneficial to industrialized production.
The high efficiency extraction technique of a kind of liquaemin, it is characterised in that comprise the following steps:
(1) digest
Mucous membrane of small intestine is taken as raw material, alkali protease is added, pH to 9.0-9.5 is adjusted, 50-60 DEG C of temperature carries out enzyme
Solution;Then, add hydrochloric acid solution to adjust pH to 5.5-6.0, be warmed up to 70-75 DEG C, obtain small intestine slurries;
(2) preparation of fining agent
It is 3 by weight ratio:7-7:3 glyceryl monostearate and palmitic acid mixing, is warmed up to 70-75 DEG C and melts and stir
Uniformly, fining agent is obtained standby;
(3) adsorb
To melt in fining agent addition small intestine slurries, carry out insulated and stirred;
(4) standing separation
The feed liquid that step (3) is obtained stands, and occurs substantially layering after a period of time;Upper strata is for after fining agent adsorbing contaminant
The semi-solid thing of formation, lower floor is clear light yellow solution, extracts lower floor's solution, filtering, regulation filtrate temperature to 55-65
DEG C, add 20kg sodium chloride fully to dissolve by every 1000L feed liquids, add resin, after the completion of absorption, dry adsorbent;With 60-65 DEG C
Water is rinsed twice, then adds 60-65 DEG C of 3mol/L sodium chloride solutions stirring to elute 2-3 times;Wherein, the addition of 20kg sodium chloride is suppression
The resin adsorption impurity that system is added below;
(5) drying is precipitated
Add ethanol to be precipitated, dehydrate, obtain final product crude heparin sodium.
The beneficial effect of this technique is used as fining agent by the use of glyceryl monostearate and palmitic acid, this method
From original before being, this fining agent can significantly adsorb the impurity such as grease, the protein in mucous membrane of small intestine, have
Effect separates liquaemin and protein impurities, and the effect than simple use glyceryl monostearate or palmitic acid is more preferable.Fining agent
The light yellow transparent solution that can be clarified of addition, compared to tree is directly added in traditional handicraft in mucous membrane of small intestine slurry
Fat is adsorbed.
Further, after being processed through step (4), to pure water ultrafiltration 3-5 times is added in feed liquid repeatedly, dioxygen water oxygen is added
Change, then carry out step (5), refined heparin sodium can be obtained.
Further, in step (1), the time of enzymolysis is 3-4h.
Further, in step (3), the ratio of small intestine enzymolysis liquid and fining agent is 1000L:10-15kg.
Further, in step (3), mixing speed is 40-60r/min, and mixing time is 0.5-1h.
Further, in step (3), mixing speed is 50r/min, and mixing time is 1h.
Further, in step (3), filtrate temperature is adjusted by addition water in filtrate.
Further, the concentration of ethanol is added to be not less than 88%, 0.9 times of volume more than effluent volume.
Further, the concentration of hydrogen peroxide is 27-30%, and volume is the 1.0-2.0% of cumulative volume.
To sum up, the present invention can greatly reduce using and polluting for resin, with high income, waste liquid be few, environmental pollution
The advantages of small, waste liquid is easily processed, is adapted to industrialized production, with social and economic benefit.
Specific embodiment
Principle of the invention and feature are described below, example is served only for explaining the present invention, is not intended to limit
Determine the scope of the present invention.
Embodiment 1
The high efficiency extraction technique of a kind of liquaemin, it is characterised in that comprise the following steps:
(1) digest
Mucous membrane of small intestine is taken as raw material, alkali protease is added, pH to 9.0 is adjusted, temperature 50 C digests 4h;Then, plus
Enter hydrochloric acid solution and adjust pH to 6.0, be warmed up to 70 DEG C, obtain small intestine slurries;
(2) preparation of fining agent
It is 3 by weight ratio:7 glyceryl monostearate and palmitic acid mixing, is warmed up to 70 DEG C and melts and stir, and obtains
It is standby to fining agent;
(3) adsorb
Ratio according to small intestine enzymolysis liquid and fining agent is 1000L:The ratio mixing of 10kg, insulated and stirred;Mixing speed
It is 40r/min, mixing time is 1h.
(4) standing separation
The feed liquid that step (3) is obtained stands, and occurs substantially layering after a period of time;Upper strata is for after fining agent adsorbing contaminant
The semi-solid thing of formation, lower floor is clear light yellow solution, extracts lower floor solution, filtering, add water adjust filtrate temperature to
55 DEG C, add 20kg sodium chloride fully to dissolve by every 1000L feed liquids, add resin, after the completion of absorption, dry adsorbent;With 60 DEG C
Water is rinsed twice, then adds 60 DEG C of 3mol/L sodium chloride solutions stirrings to elute 2-3 times;Wherein, the addition of 20kg sodium chloride is to suppress
The resin adsorption impurity for adding below;
(5) aoxidize
To pure water ultrafiltration 3-5 times is added in feed liquid repeatedly, it is 27% to add concentration, and volume is the 2.0% of cumulative volume
Hydrogen peroxide oxidation;
(6) drying is precipitated
To adding concentration to be 88% in the feed liquid after oxidation, volume is sunk for 0.97 times of effluent volume of ethanol
Form sediment, dehydrate, obtain final product liquaemin.
Embodiment 2
The high efficiency extraction technique of a kind of liquaemin, it is characterised in that comprise the following steps:
(1) digest
Mucous membrane of small intestine is taken as raw material, alkali protease is added, pH to 9.5 is adjusted, temperature 60 C digests 3h;Then, plus
Enter hydrochloric acid solution and adjust pH to 5.5, be warmed up to 75 DEG C, obtain small intestine slurries;
(2) preparation of fining agent
It is 7 by weight ratio:3 glyceryl monostearate and palmitic acid mixing, is warmed up to 75 DEG C and melts and stir, and obtains
It is standby to fining agent;
(3) adsorb
Ratio according to small intestine enzymolysis liquid and fining agent is 1000L:The ratio mixing of 15kg, insulated and stirred;Mixing speed
It is 60r/min, mixing time is 0.5h.
(4) standing separation
The feed liquid that step (3) is obtained stands, and occurs substantially layering after a period of time;Upper strata is for after fining agent adsorbing contaminant
The semi-solid thing of formation, lower floor is clear light yellow solution, extracts lower floor solution, filtering, add water adjust filtrate temperature to
65 DEG C, add 20kg sodium chloride fully to dissolve by every 1000L feed liquids, add resin, after the completion of absorption, dry adsorbent;With 65 DEG C
Water is rinsed twice, then adds 65 DEG C of 3mol/L sodium chloride solutions stirrings to elute 2-3 times;Wherein, the addition of 20kg sodium chloride is to suppress
The resin adsorption impurity for adding below;
(5) aoxidize
To pure water ultrafiltration 3-5 times is added in feed liquid repeatedly, it is 30% to add concentration, and volume is the 1.0% of cumulative volume
Hydrogen peroxide oxidation;
(6) drying is precipitated
To adding concentration to be 95% in the feed liquid after oxidation, volume is precipitated for 0.9 times of effluent volume of ethanol,
Dehydrate, obtain final product liquaemin.
Both examples above, every small intestine is reduced to 5g using the amount of resin by traditional 20g.Additionally, liquaemin is imitated
Valency reaches more than 160usp/mg.
The foregoing is only presently preferred embodiments of the present invention, be not intended to limit the invention, it is all it is of the invention spirit and
Within principle, any modification, equivalent substitution and improvements made etc. should be included within the scope of the present invention.
Claims (9)
1. the high efficiency extraction technique of a kind of liquaemin, it is characterised in that comprise the following steps:
(1) digest
Mucous membrane of small intestine is taken as raw material, alkali protease is added, pH to 9.0-9.5 is adjusted, 50-60 DEG C of temperature is digested;So
Afterwards, add hydrochloric acid solution to adjust pH to 5.5-6.0, be warmed up to 70-75 DEG C, obtain small intestine slurries;
(2) preparation of fining agent
It is 3 by weight ratio:7-7:3 glyceryl monostearate and palmitic acid mixing, is warmed up to 70-75 DEG C and melts and stir
It is even, obtain fining agent standby;
(3) adsorb
To melt in fining agent addition small intestine slurries, carry out insulated and stirred;
(4) standing separation
The feed liquid that step (3) is obtained stands, and occurs substantially layering after a period of time;Lower floor is clear light yellow solution, is extracted
Lower floor's solution, filtering, regulation filtrate temperature adds 20kg sodium chloride fully to dissolve to 55-65 DEG C by every 1000L feed liquids, adds
Resin, after the completion of absorption, dry adsorbent;Rinsed twice with 60-65 DEG C of water, then add 60-65 DEG C of 3mol/L sodium chloride solutions stirring
Wash-out 2-3 times;
(5) drying is precipitated
Add ethanol to be precipitated, dehydrate, obtain final product crude heparin sodium.
2. the high efficiency extraction technique of liquaemin according to claim 1, it is characterised in that after being processed through step (4), to
Add pure water ultrafiltration 3-5 times in feed liquid repeatedly, add hydrogen peroxide oxidation, then carry out step (5), refined heparin sodium can be obtained.
3. the high efficiency extraction technique of liquaemin according to claim 1, it is characterised in that in step (1), enzymolysis when
Between be 3-4h.
4. the high efficiency extraction technique of liquaemin according to claim 1, it is characterised in that in step (3), small intestine enzymolysis
The ratio of liquid and fining agent is 1000L:10-15kg.
5. the high efficiency extraction technique of liquaemin according to claim 1, it is characterised in that in step (3), mixing speed
It is 40-60r/min, mixing time is 0.5-1h.
6. the high efficiency extraction technique of liquaemin according to claim 5, it is characterised in that in step (3), mixing speed
It is 50r/min, mixing time is 1h.
7. the high efficiency extraction technique of liquaemin according to claim 1, it is characterised in that in step (3), by filter
Water regulation filtrate temperature is added in liquid.
8. the high efficiency extraction technique of liquaemin according to claim 1, it is characterised in that add the concentration of ethanol for not low
In 88%, 0.9 times of volume more than effluent volume.
9. the high efficiency extraction technique of liquaemin according to claim 2, it is characterised in that the concentration of hydrogen peroxide is 27-
30%, volume is the 1.0-2.0% of cumulative volume.
Priority Applications (1)
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CN201710161939.XA CN106916235B (en) | 2017-03-17 | 2017-03-17 | A kind of high efficiency extraction technique of heparin sodium |
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CN201710161939.XA CN106916235B (en) | 2017-03-17 | 2017-03-17 | A kind of high efficiency extraction technique of heparin sodium |
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CN106916235A true CN106916235A (en) | 2017-07-04 |
CN106916235B CN106916235B (en) | 2018-11-27 |
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Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1531436A (en) * | 2001-05-09 | 2004-09-22 | (株)美大富历寿 | Formulation of amphiphilic heparin derivatives for enhancing mucosal absorption |
CN1854282A (en) * | 2005-04-26 | 2006-11-01 | 张国志 | Sulfuric acid chondroitin wine |
CN101215339A (en) * | 2008-01-11 | 2008-07-09 | 张国志 | Method for purifying sodium chondroitin sulfate |
CN101805764A (en) * | 2010-04-02 | 2010-08-18 | 扬州大学 | High-efficiency extraction technology of heparin sodium |
CN102952204A (en) * | 2012-10-09 | 2013-03-06 | 江苏联众肠衣有限公司 | Novel production technique of heparin sodium |
CN204479047U (en) * | 2015-01-21 | 2015-07-15 | 奇瑞汽车股份有限公司 | A kind of positioning bogie fixture measures bracing or strutting arrangement |
CN107641164A (en) * | 2017-09-28 | 2018-01-30 | 东华大学 | A kind of non-homogeneous polymerization catalyst and its application in homopolymer and copolymer is prepared |
-
2017
- 2017-03-17 CN CN201710161939.XA patent/CN106916235B/en not_active Expired - Fee Related
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1531436A (en) * | 2001-05-09 | 2004-09-22 | (株)美大富历寿 | Formulation of amphiphilic heparin derivatives for enhancing mucosal absorption |
CN1854282A (en) * | 2005-04-26 | 2006-11-01 | 张国志 | Sulfuric acid chondroitin wine |
CN101215339A (en) * | 2008-01-11 | 2008-07-09 | 张国志 | Method for purifying sodium chondroitin sulfate |
CN101805764A (en) * | 2010-04-02 | 2010-08-18 | 扬州大学 | High-efficiency extraction technology of heparin sodium |
CN102952204A (en) * | 2012-10-09 | 2013-03-06 | 江苏联众肠衣有限公司 | Novel production technique of heparin sodium |
CN204479047U (en) * | 2015-01-21 | 2015-07-15 | 奇瑞汽车股份有限公司 | A kind of positioning bogie fixture measures bracing or strutting arrangement |
CN107641164A (en) * | 2017-09-28 | 2018-01-30 | 东华大学 | A kind of non-homogeneous polymerization catalyst and its application in homopolymer and copolymer is prepared |
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