CN102276742A - Method for cleanly producing MMW (medium molecular weight) hydroxyethyl starches - Google Patents
Method for cleanly producing MMW (medium molecular weight) hydroxyethyl starches Download PDFInfo
- Publication number
- CN102276742A CN102276742A CN2011102267850A CN201110226785A CN102276742A CN 102276742 A CN102276742 A CN 102276742A CN 2011102267850 A CN2011102267850 A CN 2011102267850A CN 201110226785 A CN201110226785 A CN 201110226785A CN 102276742 A CN102276742 A CN 102276742A
- Authority
- CN
- China
- Prior art keywords
- molecular weight
- hydroxyethyl starch
- weight hydroxyethyl
- hydroxyethylamyle
- production method
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
The invention provides a method for cleanly producing MMW (medium molecular weight) hydroxyethyl starches and in particular relates to a clean production method for a refine technology of chemical raw materials such as hydroxyethyl starches 200/0.5 and hydroxyethyl starches 130/04 for blood plasma expanders. Bacterial endotoxins are the key poisonous substances causing the clinical transfusion pyrogen reaction. Bacterial endotoxins of hydroxyethyl starch BPCs (bulk pharmaceutical chemicals) exceed the limitation, thus the bacterial endotoxins in final hydroxyethyl starch injecta exceed the limitation easily and the failure rate is increased. In the method, by the controls of necessary technological conditions such as clean wind spray drying under the clean condition, microorganism control under the high-temperature condition, online washing and disinfection of equipment and the like, the index quality of the bacterial endotoxins of the final product is superior to that in existing state drug quality standards obviously. Meanwhile, the necessary conditions of a method that the BPCs are used to prepare drugs directly without microfiltration are provided, thus being beneficial to qualifying the indexes of insoluble particles of the drugs, shortening processes of the final preparation technology, and reducing the probability of pollutions.
Description
Technical field
The invention belongs to field of medicine and chemical technology, the production method of molecular weight hydroxyethyl starch in being specifically related to.
Background technology
The major physiological function of plasma expander is to keep normal plasma colloid osmotic pressure and expand plasma volume, improves Hemodynamics, microcirculation blood flow, hemorheology and oxygen and supplies and organ dysfunction.Be used to give treatment to because of the shock of bleeding profusely, burning or other wound causing.The ideal plasma expander, can replenish the Q volume of blood of losing fast, recover hemodynamic balance, recover normal microcirculation blood flow, improve hemorheology, improve oxygen supply and organ dysfunction, the residence time and good tolerability in the sufficiently long blood vessel are arranged, and in vivo easily by metabolism and discharge.
At present, plasma expander commonly used clinically both at home and abroad has medicines such as hydroxyethylamyle (HES), dextran, glucose, fructose, sodium salt, plasma proteins, albumin.1887, salts solution was used to give treatment to hemorrhagic shock first, and subsequently, various salts solutions are widely used in clinical, but excessive input can reduce plasma colloid osmotic pressure and cause tissue edema; 1915, gelatin solution was used to clinical for the first time, but a little less than discovering that its dilatation, untoward reaction is comparatively serious; 1945, dextran began to be used for clinical, and is though dilatation is stronger, influential to thrombin and renal function; The albumin clinical efficacy is better, yet it is limited to originate; Hydroxyethylamyle (HES) from introduced in 1962 clinical since, go through 30 surplus year owing to constantly regenerate and upgrade, become the most popular plasma expander of American-European countries gradually.
The high branch of the raw material of this series products amylopectin is made behind acid hydrolysis, hydroxyethylation by high branch amylopectin from waxy corn, molecular weight low degree of substitution hydroxyethylamyle in the genus.Chemical name is: poly-(oxygen-2-hydroxyethyl) starch, its general hydroxyethylamyle 200/0.5 by name (Mw is 180,000 to 290,000, MS be 0.43 to 0.55); Hydroxyethylamyle 130/0.4 (Mw is 110,000 to 150,000, MS be 0.38 to 0.45).Chemical structural formula is as scheming:
R2, R3=H or CH
2CH
2OH, R2, R3 can be identical or inequality
R6=H or CH
2CH
2OH or be the tapping point of 1,6 glycosidic link
The repeating structure number of n=glucose unit or hydroxyethyl glucose unit is 80 to 3000 as the concentrated scope of the n value of hydroxyethylamyle 130/0.4, and the concentrated scope of the n value of hydroxyethylamyle 200/0.5 is 80 to 5000.
Bacterial endotoxin is the crucial toxicant that causes the clinical transfusion pyrogen reaction.Bacterial endotoxin and hydroxyethylamyle belong to polysaccharide together, molecular weight is approaching, the characteristics that physico-chemical property height unanimity is arranged, in case the bulk drug bacterial endotoxin occurring transfinites, be difficult in the preparation process remove by traditional Medicinal Charcoal processing mode, to be easy to cause that bacterial endotoxin transfinites in the preparation the finished product hydroxyethyl starch injection liquid, disqualification rate raises.Simultaneously in American-European countries's injection liquid processing, use the Medicinal Charcoal processing mode rare, therefore to the bacterial endotoxin in the bulk drug in addition strict limit very necessary.As the bacterial endotoxin limit 2.5EU/ml～5.0EU/ml of hydroxyethyl starch injection liquid, corresponding solid material limit should be 4EU/g～8EU/g.In fact, the qualified suitable condition of being prepared of hydroxyethyl starch injection liquid bacterial endotoxin 5.0EU/ml is to use the bulk drug bacterial endotoxin to be lower than 5EU/g, the qualified suitable condition of being prepared of hydroxyethyl starch injection liquid bacterial endotoxin 2.5EU/ml is to use the bulk drug bacterial endotoxin to be lower than 1.25EU/g, and above-mentioned raw material bacterial endotoxin limit requires more existing national standard limit 5.0EU/g～10EU/g more strict.
Itself has trophicity hydroxyethylamyle, very easily makes to cause bacterial reproduction, bacterial reproduction occurs and will cause bacterial endotoxin to become hundred times increasing rapidly.Therefore should strict control cleaning condition in the production technique of hydroxyethylamyle.
In a single day bacterial endotoxin enters medicine, usually the method for removing is heat-flash, highly basic, strong acid treatment, hydroxyethylamyle can't tolerate such exacting terms in process for refining, the production of these ways and inapplicable hydroxyethylamyle bulk drug, to effectively remove intracellular toxin above 170 ℃ of ability as heat-flash, hydroxyethylamyle will produce charing under this condition; Strong acid or highly basic processing can cause production of by-products.
Summary of the invention
Task of the present invention provides a kind of clean production method of middle molecular weight hydroxyethyl starch, and described middle molecular weight hydroxyethyl starch comprises hydroxyethylamyle 200/0.5 and hydroxyethylamyle 130/0.4, for being used for the medicinal chemicals of plasma expander.
Realize that technical scheme of the present invention is:
Molecular weight hydroxyethyl starch clean production method in provided by the invention may further comprise the steps:
A: the equipment on-line cleaning is sterilized;
B: the middle molecular weight hydroxyethyl starch crude product aqueous solution is carried out the Medicinal Charcoal decolouring;
C: the middle molecular weight hydroxyethyl starch crude product aqueous solution is carried out millipore filtration;
D: the middle molecular weight hydroxyethyl starch crude product aqueous solution is carried out the ultra micro membrane sepn;
E: the middle molecular weight hydroxyethyl starch aqueous solution after the above-mentioned steps is carried out clean wind spraying drying, molecular weight hydroxyethyl starch in getting.
The above steps order can be
A → B → C → D → E or
A → D → B → C → E or
A → B → C → DC → E, wherein DC represents that ultra micro membrane sepn and millipore filtration carry out simultaneously.
The molecular weight hydroxyethyl starch crude product aqueous solution is meant that the millipore filtration of all or part of process, Medicinal Charcoal decolouring, ultra micro membrane sepn purified do not contain the intermediate above drug standard limit impurity in described.
Molecular weight hydroxyethyl starch clean production method in provided by the invention, concrete order and method can be:
(a) the equipment on-line cleaning is sterilized;
(b) the ultra micro membrane sepn process that to be 5%～15% the middle molecular weight hydroxyethyl starch crude product aqueous solution with hydroxyethylamyle content form through 304 types or other stainless steel pipes valve of higher level;
(c) the hydroxyethylamyle content behind the ultra micro membrane sepn is that 5%～15% the part of damming is decoloured through Medicinal Charcoal, the Medicinal Charcoal destainer;
(d) the Medicinal Charcoal destainer is again through the millipore filtration of 0.15--0.8 micron;
(e) millipore filtration liquid is 15%～40% o'clock through being concentrated into hydroxyethylamyle content, again through clean wind spraying drying, and molecular weight hydroxyethyl starch in getting.
Molecular weight hydroxyethyl starch clean production method in provided by the invention, concrete order and method can also be:
(1) the equipment on-line cleaning is sterilized;
(2) be that 5%～15% the middle molecular weight hydroxyethyl starch crude product aqueous solution decolours through Medicinal Charcoal with hydroxyethylamyle content, the Medicinal Charcoal destainer;
(3) the Medicinal Charcoal destainer keeps 60 ℃-100 ℃, after the millipore filtration of 0.15--0.8 micron, hydroxyethylamyle content is 5%～15% millipore filtration liquid;
(4) with hydroxyethylamyle content be the ultra micro membrane sepn that 5%～15% millipore filtration liquid is formed through 304 types or other stainless steel pipes valve of higher level again, the part of damming of ultra micro membrane sepn;
(5) the ultra micro membrane sepn dam part after concentrating hydroxyethylamyle content is 15%～40% concentrated solution, again through clean wind spraying drying, in molecular weight hydroxyethyl starch.
Molecular weight hydroxyethyl starch clean production method in provided by the invention, concrete order and method can also be:
1. the equipment on-line cleaning is sterilized;
2. be that 5%～15% the middle molecular weight hydroxyethyl starch crude product aqueous solution decolours through Medicinal Charcoal with hydroxyethylamyle content, the Medicinal Charcoal destainer;
3. hydroxyethylamyle content is that 5%～15% Medicinal Charcoal destainer keeps 60 ℃-100 ℃, and the micropore filter element filtration through the 0.15--0.8 micron gets millipore filtration liquid;
4. millipore filtration liquid is again through the ultra micro membrane sepn of 304 types or other stainless steel pipes valve composition of higher level, and ultra-filtration membrane is isolating to carry out the micropore filter element filtration to ultra micro membrane sepn trapped fluid simultaneously;
5. the ultra micro membrane sepn dam part after concentrating hydroxyethylamyle content be 15%～40% concentrated solution, clean wind spraying drying, in molecular weight hydroxyethyl starch.
The weight-average molecular weight of molecular weight hydroxyethyl starch is 100,000 to 500,000 in of the present invention.
Molecular weight hydroxyethyl starch specifically can be hydroxyethylamyle 130/0.4 or hydroxyethylamyle 200/0.5 in of the present invention, and the weight-average molecular weight of hydroxyethylamyle 130/0.4 is 110,000 to 150,000; The weight-average molecular weight of hydroxyethylamyle 200/0.5 is 150,000 to 300,000.
In above-mentioned middle molecular weight hydroxyethyl starch clean production method, middle molecular weight hydroxyethyl starch crude product solution keeps 60 ℃-100 ℃ when millipore filtration separates with ultra-filtration membrane, preferred 70 ℃-90 ℃.
In above-mentioned middle molecular weight hydroxyethyl starch clean production method, the solvent that production process adds is the water for injection of purified water or intracellular toxin limit 1.25EU/ml.
The invention has the advantages that polishing product bacterial endotoxin limit value is lower than 1.25EU/g～2.5EU/g, be adapted to the actual needs that hydroxyethyl starch injection liquid is produced, far above existing domestic medicine registered standard limit 5EU/g～10EU/g.
Bibliographical information hydroxyethylamyle process for refining comprises ultra micro membrane sepn, millipore filtration, dry serial process [referring to US5,218,108, Jun.8,1993.], and above-mentioned report there is no the key index bacterial endotoxin in the medicinal chemicals product and touches upon.
The invention provides a kind of clean production method in process for refining, hydroxyethylamyle crude reaction process the following step: hyperfiltration, Medicinal Charcoal decolouring, millipore filtration, drying, make the finished product hydroxyethylamyle 200/0.5 and hydroxyethylamyle 130/0.4, the solvent that uses in the technology should be finished in 6h as purified water or water for injection, the treating process except that drying.In the above-mentioned treating process, the material solution fluid can be smooth production process should keep clean state by equipment, isolate with exogenous biological pollution or avoid microbial reproduction, all carry out the on-line cleaning sterilization after every batch of production.Drying process adopts the spray-drying process under the purifying treatment air conditions.
Select to have the ABS of health grade standard or tubular fibre or the ceramic super-filtering film and the corresponding pipe fitting valve of stainless steel pipes main body in the ultra filtration method that the present invention adopts, fluid can smoothness pass through equipment, easily flushing regeneration is used, preferred pipeline, valve, the housing of stainless steel grade more than 304 types that use, so selection can be avoided because of medicine microbiological contamination and the drug residue located such as pipeline dead angle in process of production.
The micro-filtration process adopts the micropore filter element or the filter membrane of 0.15～0.8 micron pore size among the present invention, preferred 0.22～0.65 micron pore size, the prerequisite of bulk drug without the direct formulated method of micro-filtration is provided, guarantee the qualified of preparation particulate matter index, such way has shortened final preparation process flow process, reduce the probability of polluting, be convenient to preparation production.
All adopting purified water or water for injection among the present invention in subsequent steps such as hyperfiltration and micro-filtration is solvent, and the preferred bacterium intracellular toxin is lower than the water for injection of 1.25EU/g, has reduced the possibility of introducing bacterial endotoxin because of solvent to greatest extent.
In the operation time limit of finishing in the required 6h of the treating process except that drying of the present invention, purpose is by shortening the treatment time of material fluid state in pipeline, having reduced the generation possibility that causes bacterial endotoxin because of the biological load increase;
Proposed among the present invention that hydroxyethyl starch solution remains on 60-100 ℃ in the treating process, preferred 70-90 ℃, this is based on hydroxyethylamyle and has thermostability under this temperature, has reduced simultaneously because of biological load and has increased the generation possibility that causes bacterial endotoxin;
Proposed hydroxyethyl starch solution among the present invention when carrying out ultra-filtration process, serial or parallel carries out the millipore filtration process, preferred parallel procedure, and the mode of this ultrafiltration and micro-filtration combination has significantly reduced the inoculating microbe that system itself may bring.
Embodiment
Embodiment 1
100Kg contains 15% crude product solution of hydroxyethylamyle 130/0.4 to be handled through the tubular fibre ultra micro film of 304 type pipeline valves composition, and the part of damming is filtered through 0.45 micron micropore filter element after the Medicinal Charcoal decolouring is handled, so far, treatment time 5.5h, clean wind spraying drying, final product 70Kg.
Products therefrom is lower than bacterial endotoxin limit value 1.25EU/g, product solution (5%) clear, colorless, reach 2010 editions No. 1 turbidity liquid standards of Chinese Pharmacopoeia, 400nm place absorbancy 0.012, be better than national drug quality standard (bacterial endotoxin limit value 5EU/g, No. 1 turbidity liquid, 400nm place absorbancy 0.05).Other index all meets medicinal standard.
Embodiment 2
20% crude product solution that contains 100Kg hydroxyethylamyle 200/0.5 is after the Medicinal Charcoal decolouring is handled, keep 80 ℃, after 0.8 micron micropore filter element filters, the ceramic membrane ultrafitration film of forming through 304 type stainless steel pipes valves is handled again, it is purified water (intracellular toxin limit 2.5EU/ml) that treating processes adds solvent, so far, and treatment time 4.5h, clean wind spraying drying, final product 73Kg.Above-mentioned technological process repeats to implement secondary, all to the sterilization of equipment on-line cleaning, gets final product 85Kg and 66Kg respectively before each the enforcement.
Three batches of final products of gained are lower than bacterial endotoxin limit value 2.5EU/g, product solution (5%) transparent color is shallow, reach 2010 editions No. 2 turbidity liquid standards of Chinese Pharmacopoeia, 400nm place absorbancy 0.034,0.028,0.022, reach national drug quality standard (bacterial endotoxin limit value 8EU/g, No. 2 turbidity liquid, 400nm place absorbancy 0.058).Other index all meets medicinal standard.
Embodiment 3
20% crude product solution that contains 100Kg hydroxyethylamyle 200/0.5 is after the Medicinal Charcoal decolouring is handled, keep 80 ℃, after 0.8 micron micropore filter element filters, the ceramic super-filtering film of forming through 304 type stainless steel pipes valves is handled again, the parallel simultaneously micropore filter element filtering system that is connected to 0.45 micron, and it is water for injection (intracellular toxin limit 1.25EU/ml) that process adds solvent, so far, treatment time 4.5h, clean wind spraying drying, final product 73Kg.
Final product is lower than bacterial endotoxin limit value 1.25EU/g, product solution (5%) transparent color is shallow, reach 2010 editions No. 1 turbidity liquid standards of Chinese Pharmacopoeia, 400nm place absorbancy 0.010, reach national drug quality standard (bacterial endotoxin limit value 8EU/g, No. 2 turbidity liquid, 400nm place absorbancy 0.058).Other index all meets medicinal standard.
Claims (10)
1. molecular weight hydroxyethyl starch clean production method in a kind is characterized in that, may further comprise the steps:
A: the equipment on-line cleaning is sterilized;
B: the middle molecular weight hydroxyethyl starch crude product aqueous solution is carried out the Medicinal Charcoal decolouring;
C: the middle molecular weight hydroxyethyl starch crude product aqueous solution is carried out millipore filtration;
D: the middle molecular weight hydroxyethyl starch crude product aqueous solution is carried out the ultra micro membrane sepn;
E: the middle molecular weight hydroxyethyl starch aqueous solution after the above-mentioned steps is carried out clean wind spraying drying, molecular weight hydroxyethyl starch in getting;
The above steps order can be:
A→B→C→D→E
Or
A→D→B→C→E
Or
A → B → C → DC → E, wherein DC represents that ultra micro membrane sepn and millipore filtration carry out simultaneously.
2. molecular weight hydroxyethyl starch clean production method in a kind is characterized in that, order is as follows:
(a) the equipment on-line cleaning is sterilized;
(b) the ultra micro membrane sepn process that to be 5%～15% the middle molecular weight hydroxyethyl starch crude product aqueous solution with hydroxyethylamyle content form through 304 types or other stainless steel pipes valve of higher level;
(c) the hydroxyethylamyle content behind the ultra micro membrane sepn is that 5%～15% the part of damming is decoloured through Medicinal Charcoal, the Medicinal Charcoal destainer;
(d) the Medicinal Charcoal destainer is again through the millipore filtration of 0.15-0.8 micron;
(e) millipore filtration liquid is 15%～40% o'clock through being concentrated into hydroxyethylamyle content, again through clean wind spraying drying, and molecular weight hydroxyethyl starch in getting.
3. molecular weight hydroxyethyl starch clean production method in a kind is characterized in that, order is as follows:
(1) the equipment on-line cleaning is sterilized;
(2) be that 5%～15% the middle molecular weight hydroxyethyl starch crude product aqueous solution decolours through Medicinal Charcoal with hydroxyethylamyle content, the Medicinal Charcoal destainer;
(3) the Medicinal Charcoal destainer keeps 60 ℃-100 ℃, after the millipore filtration of 0.15--0.8 micron, hydroxyethylamyle content is 5%～15% millipore filtration liquid;
(4) with hydroxyethylamyle content be the ultra micro membrane sepn that 5%～15% millipore filtration liquid is formed through 304 types or other stainless steel pipes valve of higher level again, the part of damming of ultra micro membrane sepn;
(5) the ultra micro membrane sepn dam part after concentrating hydroxyethylamyle content is 15%～40% concentrated solution, again through clean wind spraying drying, in molecular weight hydroxyethyl starch.
4. molecular weight hydroxyethyl starch clean production method in a kind is characterized in that, order is as follows:
1. the equipment on-line cleaning is sterilized;
2. be that 5%～15% the middle molecular weight hydroxyethyl starch crude product aqueous solution decolours through Medicinal Charcoal with hydroxyethylamyle content, the Medicinal Charcoal destainer;
3. hydroxyethylamyle content is that 5%～15% Medicinal Charcoal destainer keeps 60 ℃-100 ℃, and the micropore filter element filtration through the 0.15--0.8 micron gets millipore filtration liquid;
4. millipore filtration liquid is again through the ultra micro membrane sepn of 304 types or other stainless steel pipes valve composition of higher level, and ultra-filtration membrane is isolating to carry out the micropore filter element filtration to ultra micro membrane sepn trapped fluid simultaneously;
5. the ultra micro membrane sepn dam part after concentrating hydroxyethylamyle content be 15%～40% concentrated solution, clean wind spraying drying, in molecular weight hydroxyethyl starch.
5. according to each described middle molecular weight hydroxyethyl starch clean production method in the claim 1 to 4, it is characterized in that the weight-average molecular weight of described middle molecular weight hydroxyethyl starch is 100,000 to 500,000.
6. according to each described middle molecular weight hydroxyethyl starch clean production method in the claim 1 to 4, it is characterized in that described middle molecular weight hydroxyethyl starch is hydroxyethylamyle 130/0.4 or hydroxyethylamyle 200/0.5.
7. molecular weight hydroxyethyl starch clean production method in according to claim 5 is characterized in that, the weight-average molecular weight of described middle molecular weight hydroxyethyl starch is 110,000 to 150,000 or 150,000 to 300,000.
8. according to each described middle molecular weight hydroxyethyl starch clean production method in the claim 1 to 4, it is characterized in that the solvent that production process adds is the water for injection of purified water or intracellular toxin limit 1.25EU/ml.
9. according to each described middle molecular weight hydroxyethyl starch clean production method in the claim 1 to 4, it is characterized in that middle molecular weight hydroxyethyl starch crude product solution keeps 60 ℃-100 ℃ when millipore filtration separates with ultra-filtration membrane.
10. molecular weight hydroxyethyl starch clean production method in according to claim 9 is characterized in that, middle molecular weight hydroxyethyl starch crude product solution when millipore filtration separates with ultra-filtration membrane 70 ℃-90 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102267850A CN102276742A (en) | 2011-08-09 | 2011-08-09 | Method for cleanly producing MMW (medium molecular weight) hydroxyethyl starches |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102267850A CN102276742A (en) | 2011-08-09 | 2011-08-09 | Method for cleanly producing MMW (medium molecular weight) hydroxyethyl starches |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102276742A true CN102276742A (en) | 2011-12-14 |
Family
ID=45102517
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011102267850A Pending CN102276742A (en) | 2011-08-09 | 2011-08-09 | Method for cleanly producing MMW (medium molecular weight) hydroxyethyl starches |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102276742A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102631842A (en) * | 2012-04-12 | 2012-08-15 | 江苏久吾高科技股份有限公司 | Method for removing endotoxin in biological pharmaceutical preparations |
| CN102675477A (en) * | 2012-05-24 | 2012-09-19 | 河北科技大学 | Preparation method capable of improving yield of medium-molecular-weight hydroxyethyl starch |
| CN104277126A (en) * | 2013-07-11 | 2015-01-14 | 北大方正集团有限公司 | Method for purifying hydroxyethyl starch |
| CN111215017A (en) * | 2019-12-10 | 2020-06-02 | 山东省鲁洲食品集团有限公司 | Device and method for preventing liquid dextrin from aging in storage process |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1840547A (en) * | 2005-12-29 | 2006-10-04 | 天津协和生物科技发展有限公司 | Method for preparing hydroxyethyl starch with different molecular weight and different substitution degree |
| CN101402690A (en) * | 2008-09-27 | 2009-04-08 | 杭州民生药业集团有限公司 | Method for preparation of hydroxyethyl starch |
| CN101450075A (en) * | 2007-11-30 | 2009-06-10 | 成都正康药业有限公司 | Hydroxyethyl starch 130/0.4 sodium chloride injection and preparation method and use thereof |
| CN101775076A (en) * | 2010-02-25 | 2010-07-14 | 成都青山利康药业有限公司 | Method for preparing hydroxyethyl starch |
| CN102086234A (en) * | 2009-12-07 | 2011-06-08 | 重庆大新药业股份有限公司 | Preparation method for improving quality of medium molecular weight hydroxyethyl starch |
-
2011
- 2011-08-09 CN CN2011102267850A patent/CN102276742A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1840547A (en) * | 2005-12-29 | 2006-10-04 | 天津协和生物科技发展有限公司 | Method for preparing hydroxyethyl starch with different molecular weight and different substitution degree |
| CN101450075A (en) * | 2007-11-30 | 2009-06-10 | 成都正康药业有限公司 | Hydroxyethyl starch 130/0.4 sodium chloride injection and preparation method and use thereof |
| CN101402690A (en) * | 2008-09-27 | 2009-04-08 | 杭州民生药业集团有限公司 | Method for preparation of hydroxyethyl starch |
| CN102086234A (en) * | 2009-12-07 | 2011-06-08 | 重庆大新药业股份有限公司 | Preparation method for improving quality of medium molecular weight hydroxyethyl starch |
| CN101775076A (en) * | 2010-02-25 | 2010-07-14 | 成都青山利康药业有限公司 | Method for preparing hydroxyethyl starch |
Non-Patent Citations (1)
| Title |
|---|
| 崔良峰: "羟乙基淀粉系列产品生产常见问题及控制", 《齐鲁药事》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102631842A (en) * | 2012-04-12 | 2012-08-15 | 江苏久吾高科技股份有限公司 | Method for removing endotoxin in biological pharmaceutical preparations |
| CN102675477A (en) * | 2012-05-24 | 2012-09-19 | 河北科技大学 | Preparation method capable of improving yield of medium-molecular-weight hydroxyethyl starch |
| CN102675477B (en) * | 2012-05-24 | 2013-10-09 | 河北科技大学 | Preparation method capable of improving yield of medium-molecular-weight hydroxyethyl starch |
| CN104277126A (en) * | 2013-07-11 | 2015-01-14 | 北大方正集团有限公司 | Method for purifying hydroxyethyl starch |
| CN104277126B (en) * | 2013-07-11 | 2016-08-10 | 北大方正集团有限公司 | The method of purification of hetastarch |
| CN111215017A (en) * | 2019-12-10 | 2020-06-02 | 山东省鲁洲食品集团有限公司 | Device and method for preventing liquid dextrin from aging in storage process |
| CN111215017B (en) * | 2019-12-10 | 2021-06-25 | 山东省鲁洲食品集团有限公司 | Device and method for preventing liquid dextrin from aging in storage process |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103468766B (en) | Preparation method of high-purity mannan oligosaccharide | |
| CN100526335C (en) | Chitin oligose preparing process | |
| CN101735340B (en) | Method for preparing heparin sodium by combining enzymolysis and salt decomposition | |
| FI86141C (en) | Process for the preparation of peritoneal dialysis solution | |
| CN101663327A (en) | Produce the purification process of the shortening of streptococcus pneumoniae (STREPTOCOCCUS PNEUMONIAE) capsular polysaccharide | |
| CN101487034B (en) | Preparation of beta-poly malic acid and salt thereof | |
| CN103060295B (en) | Preparation method for chymotrypsin | |
| CN103232558B (en) | Preparation method of high-quality low-molecular weight dalteparin sodium | |
| CN102276742A (en) | Method for cleanly producing MMW (medium molecular weight) hydroxyethyl starches | |
| CN101434553B (en) | Method for all-film extraction of valine | |
| CN102070727A (en) | Extraction method of sodium heparin | |
| CN101538593A (en) | Method for coupling production of Gamma-polyglutamic acid by technologies of microbial fermentation and membrane separation | |
| JP5713995B2 (en) | Method for purifying hyaluronic acid and / or salt thereof | |
| CN100372859C (en) | Method for preparing medicinal grade cane sugar | |
| CN102167750B (en) | Preparation method of 130ethoxyl starch | |
| CN101215338B (en) | Iron isomaltum oligosaccharide and preparing method thereof | |
| CN101942039A (en) | Parnaparin production method | |
| CN112646055A (en) | Preparation method of low-molecular-weight hyaluronic acid | |
| KR101615267B1 (en) | A process for the ultrapurification of alginates | |
| CN109021095B (en) | A kind of high-purity is without fishy smell algae blue pigment and the preparation method and application thereof | |
| CN106367451A (en) | Preparation method of group A/C meningococcal polysaccharide | |
| CN102276751B (en) | Method for extracting glycosaminoglycan from bullacta exarata | |
| CN103145880B (en) | Method for removing free sulphur in enoxaparin sodium raw material | |
| CN104069019A (en) | Shampoo containing hyaluronic acid | |
| CN112321751A (en) | Refining method of high-quality enoxaparin sodium |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20111214 |