CN101607999A - A kind of preparation method of propylene glycol alginate sodium sulfate - Google Patents
A kind of preparation method of propylene glycol alginate sodium sulfate Download PDFInfo
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- CN101607999A CN101607999A CNA2009100172577A CN200910017257A CN101607999A CN 101607999 A CN101607999 A CN 101607999A CN A2009100172577 A CNA2009100172577 A CN A2009100172577A CN 200910017257 A CN200910017257 A CN 200910017257A CN 101607999 A CN101607999 A CN 101607999A
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- propylene glycol
- glycol alginate
- lalgine
- sodium sulfate
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Abstract
The present invention relates to a kind of preparation method of propylene glycol alginate sodium sulfate, with the Lalgine is raw material, finish through Over emulsfication, acidifying, esterification, sulfonation and salify processing step, belong to pharmaceutical chemicals feedstock production technical field, emulsifying raw material is that Lalgine is dissolved in the polyglycol solution after with water-wet, places colloidal mill to grind to form even oil phase repeatedly again; Change over to oil phase in the retort again and add purified water and be stirred to the formation raw emulsion; The acidifying chain rupture is that raw emulsion is added the hydrochloric acid post-heating, behind the synthesis under normal pressure feed liquid is filtered, and gets oligomeric Lalgine with the washing with alcohol after drying; Esterification is that oligomeric Lalgine is stirred after with water-wet, heat up after adding sodium hydroxide again, synthesis under normal pressure, elimination solution, solid materials with washing with alcohol three times, dry behind the suction filtration again propylene glycol alginate; Get propylene glycol alginate sodium sulfate through sulfonation and salify again, it reacts completely, the yield height, and production toxicity is little, safety and environmental protection.
Description
Technical field:
The present invention relates to a kind of preparation method of propylene glycol alginate sodium sulfate, is raw material with the Lalgine, finishes through Over emulsfication, acidifying, esterification, sulfonation and salify processing step, belongs to pharmaceutical chemicals feedstock production technical field.
Background technology:
Propylene glycol alginate sodium sulfate has heparitin sample physiologically active, can reduce the viscosity of blood, have blood coagulation resisting function and antithrombotic, reducing blood viscosity and peripheral vascular dilating effect, be mainly used in the control of transient ischemic attack such as ischemic cerebrovascular disease such as cerebral thrombosis, cerebral embolism, cerebral arteriosclerosis, apoplexy, hyperlipidemia, coronary heart disease, high blood viscosity syndrome and coronary heart disease and angina pectoris, also can be used for treating disseminated intravascular coagulation, chronic glomerulonephritis treatment.At present, the traditional processing technology method of propylene glycol alginate sodium sulfate is to be the raw material direct hydrolysis with the sodium alginate, preparation method as the disclosed a kind of propylene glycol alginate sodium sulfate of patent No.1059679C, this method can not overcome the viscosity difficult problem of starting raw material, production process is complicated and be difficult to control, product yield is low, and agents useful for same toxicity is unfavorable for operator ' s health greatly when producing, and is unfavorable for environmental protection.
Summary of the invention:
The objective of the invention is to overcome the shortcoming that exists in the prior art, seek to provide a kind of solution propylene glycol alginate sodium sulfate starting raw material viscosity height, production process is simple and easy to control, the product yield height, and also the good solvent of safety in utilization has reduced the toxic propylene glycol alginate sodium sulfate preparation method of production.
To achieve these goals, main process step of the present invention comprises emulsifying raw material processing, acidifying chain rupture processing, esterification treatment, sulfonation processing and five processes of salify, emulsifying raw material is that Lalgine is dissolved in the polyglycol solution after with water-wet, by 2: 4 part by weight slowly add polysorbas20, the tween 80 compound emulsifying agent places colloidal mill to grind to form even oil phase repeatedly again; Change over to oil phase in the retort again and add purified water and be stirred to the formation raw emulsion; The acidifying chain rupture is raw emulsion to be put into the reactor whipping process add hydrochloric acid post-heating to 100 ℃, after synthesis under normal pressure 3-5 hour feed liquid is filtered, discard the upper strata acid solution, again the beds of precipitation are filtered after do, with washing with alcohol 3-5 time, the gained material gets the oligomeric Lalgine of dry type material 55 ℃ of condition vacuum-dryings; Esterification is that propylene oxide is placed in the reactor, again oligomeric Lalgine of dry type material and water were added reactor by weight 3: 1 in the whipping process of wetting back, be warming up to 30～50 ℃ of synthesis under normal pressure 2-4 hours after adding sodium hydroxide again, emit feed liquid and remove by filter solution, solid materials with washing with alcohol three times, dry behind the suction filtration material again propylene glycol alginate; Sulfonation is propylene glycol alginate to be put into to add behind the reactor drip chlorsulfonic acid post-heating to 80～86 ℃ reaction 3-5 hour when glycol ether stirs, and the cooling back adds ethanol sedimentation, with resolution of precipitate, uses ethanol sedimentation repeatedly three times, suction filtration dry solid materials; Salify be earlier with solid materials with dissolution of sodium hydroxide and to transfer pH value be 8 to make its salify; The centrifugal throw out that gets after washing three times with ethanol sedimentation then; Again throw out is tiled on the drip pan even 55 ℃ through oven dry in 2 hours and pulverized 60 mesh sieves, control moisture is below 8%, just the raw produce propylene glycol alginate sodium sulfate.
The present invention adopts emulsifying technology to solve the viscosity influence hydrolysis reaction degree of Lalgine, be beneficial to stable, controllably prepare propylene glycol alginate sodium sulfate; Compared with prior art one is the novel method of having started the propylene glycol alginate sodium sulfate preparation, utilizes emulsifying technology to solve the high difficult problem of starting raw material viscosity, reacts completely the yield height; The 2nd, be that solvent has replaced pyridine, methane amide with low toxicity and the better glycol ether of solvability, reduced production toxicity, be beneficial to production safety and environmental protection.
Embodiment:
Embodiment below in conjunction with the concrete preparation of propylene glycol alginate sodium sulfate is further described the present invention.
Embodiment:
Present embodiment main process step comprises emulsifying raw material processing, acidifying chain rupture processing, esterification treatment, sulfonation processing and five processes of salify:
1, emulsifying raw material is handled: get Lalgine 120g, with less water wetting after, be dissolved in the polyglycol solution, slowly add polysorbas20, tween 80 (2: 4) compound emulsifying agent 2%, insert and grind 15 minutes in the colloidal mill, grind three times repeatedly and make uniform oil phase, and be transferred in the retort, adding purified water gradually, the limit edged stirs, until final formation emulsion, generally stir and promptly got raw emulsion in 30 minutes.
2, the acidifying chain rupture is handled: raw emulsion is put into reactor, add 0.6mol/L hydrochloric acid 1000ml while stirring, be heated to 100 ℃, normal pressure reacted 5 hours down, emitted feed liquid after reaction is finished, and filtered, discard the upper strata acid solution, beds of precipitation suction filtration to doing, is used washing with alcohol 3 times, and the gained material carries out 55 ℃ of vacuum-dryings.
3, esterification treatment: propylene oxide 100ml is added in the reactor, get said hydrolyzed and obtain oligomeric Lalgine 30g 10g water-wet, and in whipping process, add in the reactor, add 0.1mol/L sodium hydroxide 100ml again, be warming up to 35 ℃, synthesis under normal pressure 3 hours, emit feed liquid, filter and remove solution, with washing with alcohol 3 times of gained solid materials, dry behind the suction filtration material, obtain propylene glycol alginate.
4, sulfonation is handled: get propylene glycol alginate 30g and put into reactor, add solvent glycol ether 300ml, open and stir, drip chlorsulfonic acid 90ml, dropwise post-heating to 81-86 ℃ of reaction 4h; Postcooling is finished in reaction, adds ethanol 1000ml precipitation, with resolution of precipitate, uses ethanol sedimentation again, three times so repeatedly, gained solid materials suction filtration is dried.
5, salify: the dissolving of gained solid materials is handled in sulfonation, and with 0.1mol/L sodium hydroxide 100ml, adjust pH to 8 makes it salify; With ethanol sedimentation washing three times, washing product is later carried out centrifugal, throw out; Throw out is tiled on the drip pan, and thickness is no more than 2cm, dries material 2 hours for 55 ℃, smashes with Universalpulverizer, crosses 60 mesh sieves, and control moisture is below 8%, and the product of gained is the propylene glycol alginate sodium sulfate bulk drug; Yield 80%; Measuring with surveying polysaccharide special gel post, is standard specimen with the serial dextran of known molecular amount (weight-average molecular weight is 2500～40000), and the weight-average molecular weight that records oligomeric Lalgine is about 10000～18000.
Claims (1)
1, a kind of preparation method of propylene glycol alginate sodium sulfate, the main process step comprises emulsifying raw material, acidifying chain rupture, esterification, sulfonation and five processes of salify, it is characterized in that emulsifying raw material is that Lalgine is dissolved in the polyglycol solution after with water-wet, by 2: 4 part by weight slowly add polysorbas20, the tween 80 compound emulsifying agent places colloidal mill to grind to form even oil phase repeatedly again; Change over to oil phase in the retort again and add purified water and be stirred to the formation raw emulsion; The acidifying chain rupture is raw emulsion to be put into the reactor whipping process add hydrochloric acid post-heating to 100 ℃, after synthesis under normal pressure 3-5 hour feed liquid is filtered, discard the upper strata acid solution, again the beds of precipitation are filtered after do, with washing with alcohol 3-5 time, the gained material gets the oligomeric Lalgine of dry type material 55 ℃ of condition vacuum-dryings; Esterification is that propylene oxide is placed in the reactor, again oligomeric Lalgine of dry type material and water were added reactor by weight 3: 1 in the whipping process of wetting back, be warming up to 30～50 ℃ of synthesis under normal pressure 2-4 hours after adding sodium hydroxide again, emit feed liquid and remove by filter solution, solid materials with washing with alcohol three times, dry behind the suction filtration material again propylene glycol alginate; Sulfonation is propylene glycol alginate to be put into to add behind the reactor drip chlorsulfonic acid post-heating to 80～86 ℃ reaction 3-5 hour when glycol ether stirs, and the cooling back adds ethanol sedimentation, with resolution of precipitate, uses ethanol sedimentation repeatedly three times, suction filtration dry solid materials; Salify be earlier with solid materials with dissolution of sodium hydroxide and to transfer pH value be 8 to make its salify; The centrifugal throw out that gets after washing three times with ethanol sedimentation then; Throw out evenly is tiled on the drip pan 55 ℃ through oven dry in 2 hours and pulverized 60 mesh sieves, control moisture is below 8% again, just the raw produce propylene glycol alginate sodium sulfate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910017257 CN101607999B (en) | 2009-07-23 | 2009-07-23 | Preparation method of polysaccharide sulphate |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200910017257 CN101607999B (en) | 2009-07-23 | 2009-07-23 | Preparation method of polysaccharide sulphate |
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| CN101607999A true CN101607999A (en) | 2009-12-23 |
| CN101607999B CN101607999B (en) | 2011-06-08 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103130912A (en) * | 2011-12-02 | 2013-06-05 | 江南大学 | One-step method of preparing covalence crosslinked and hydrophobic modified sodium alga acid hydrogel |
| CN104744607A (en) * | 2015-04-22 | 2015-07-01 | 青岛正大海尔制药有限公司 | Method for preparing polysaccharide sulfate through nanofiltration technology |
| CN104774278A (en) * | 2015-04-22 | 2015-07-15 | 青岛正大海尔制药有限公司 | Method for preparing polysaccharide sulfate by virtue of electrochemical reaction |
| CN105820268A (en) * | 2015-11-25 | 2016-08-03 | 天津中津药业股份有限公司 | Preparation method and application of oligomeric sodium alginate sulfate salt |
-
2009
- 2009-07-23 CN CN 200910017257 patent/CN101607999B/en active Active
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103130912A (en) * | 2011-12-02 | 2013-06-05 | 江南大学 | One-step method of preparing covalence crosslinked and hydrophobic modified sodium alga acid hydrogel |
| CN104744607A (en) * | 2015-04-22 | 2015-07-01 | 青岛正大海尔制药有限公司 | Method for preparing polysaccharide sulfate through nanofiltration technology |
| CN104774278A (en) * | 2015-04-22 | 2015-07-15 | 青岛正大海尔制药有限公司 | Method for preparing polysaccharide sulfate by virtue of electrochemical reaction |
| CN105820268A (en) * | 2015-11-25 | 2016-08-03 | 天津中津药业股份有限公司 | Preparation method and application of oligomeric sodium alginate sulfate salt |
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| Publication number | Publication date |
|---|---|
| CN101607999B (en) | 2011-06-08 |
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