CN102766225B - A kind of piperylene gathers the preparation method of sodium sulfate and a kind of oligomeric xylose - Google Patents
A kind of piperylene gathers the preparation method of sodium sulfate and a kind of oligomeric xylose Download PDFInfo
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Abstract
The invention discloses a kind of preparation method of oligomeric xylose, it comprises the following step: xylan hydrogen peroxide, in the aqueous solution of alkali, is carried out oxidative degradation reaction by (1); (2), after the reaction of step (1) terminates, regulate reaction solution pH to be 4 ~ 7, in reaction solution, add C
1~ C
4fatty alcohol, separate out white solid, i.e. obtained oligomeric xylose; The weight-average molecular weight of described oligomeric xylose is 2000 ~ 4000; Wherein, the aqueous solution of alkali is the aqueous solution of alkaline-earth metal and/or alkali-metal oxyhydroxide, and paper mill wastewater is 1mg/ml ~ 40mg/ml; The mass ratio of alkali and xylan is 0.01 ~ 0.4; The mass ratio of hydrogen peroxide and xylan is 0.03: 1 ~ 0.3: 1; Oxidative degradation reaction temperature be 80 DEG C to reflux temperature.Preparation method of the present invention is unlike the prior art, and simple to operate, purifies easily, is suitable for industrialization, can not produce the problem that sulfate radical content reduces.
Description
Technical field
The present invention is specifically related to a kind of piperylene and gathers the preparation method of sodium sulfate and a kind of oligomeric xylose.
Background technology
The molecular weight ranges that piperylene gathers sodium sulfate [37319-17-8] is 4000-6000 (structural formula 2), is a kind ofly to treat that kidney infects, the medicine of interstitial cystitis and tumour, and produced by Ortho McNeil company, commodity are called
this product not yet goes on the market in China's Mainland.
Structural formula 2
It is a kind of semi-synthetic heparin class macromolecular carbohydrate that piperylene gathers sodium sulfate, is the tasteless powder of a kind of white, has faint water absorbability, can be water-soluble.
It is with xylan (can extract from bark) for raw material that known piperylene gathers sodium sulfate, through FOUR EASY STEPS: the first step becomes sulfuric ester, second step becomes sodium salt, the 3rd step depolymerization, the 4th step separation and purification obtain.
Patent US2689848 mentions, and xylan is through following FOUR EASY STEPS: the first step and chlorsulfonic acid, in the presence of pyridine, obtain xylan sulfuric ester; Second step and sodium hydroxide react under methanol-water mixed solvent, and obtained xylan gathers sodium sulfate; 3rd step, oxidative degradation in the acid or neutral aqueous solution, obtained depolymerization product; 4th step, depolymerization product is through dialysis method desalination, and class settling, filters the target product obtaining mentioning in patent.Target product Z
ηvalue is between 0.0030 to 0.015, and sulphur content is 13.5 to 17%.
But the content of this patent does not relate to the concrete molecular weight of its target product, but also has following shortcoming: 1, complex operation, and cost is high, and productive rate is low; 2, after second step becomes sodium salt, the product thickness obtained, inconvenient filter operation; 3, use dialysis membrane during the 4th step purifying, cannot suitability for industrialized production be adapted to.
Patent WO2009/087581 is optimized said process: in the sulfation of the first step wood sugar, uses skin Courlene (employing α, β, γ-picoline respectively) to instead of pyridine, improves yield; Become in the process of sodium salt at second step, use pure methyl alcohol as solvent, reduce post-processing difficulty; In the 4th step separation and purification, nanofiltration membrane system is used to obtain the product that molecular weight is 4000-6000.
Also there is following problem in prior art: 1, in order to obtain the product that target molecular weight is 4000-6000, must by more loaded down with trivial details purification means, and as US2689848 adopts the method for class settling, WO2009/087581 adopts nanofiltration membrane system.2, the operation of oxidative degradation is all gather the sodium sulfate stage at piperylene to carry out, and because sulfate radical is unstable, easily engaging sulphate side reaction occurs, causes the problem that degree declines.Affect drug effect for avoiding degree to decline too much, the depolymerization time must strictly control, and this causes polysaccharide chains to degrade not exclusively, makes molecular weight be that the target product productive rate of 4000-6000 is too low.(productive rate that the productive rate of US2689848 depolymehzation step is all less than 50%, WO2009/087581 depolymehzation step is all less than 55%).
Summary of the invention
Technical problem to be solved by this invention is gathered in the preparation method of sodium sulfate to overcome existing piperylene, complex operation, cost is high, and productive rate is low, the defect such as sulfate radical content reduction during depolymerization, and provide a kind of piperylene and gather the preparation method of sodium sulfate and a kind of oligomeric xylose.The present invention directly carries out oxidative degradation to xylan, owing to not having the side reactions such as engaging sulphate, can realize controlled and sufficient depolymerization; Thus obtain high yield, even molecular weight distribution and the oligomeric xylose meeted the requirements; Then sulfation is carried out to it, obtain target product.Therefore preparation method of the present invention and prior art are completely different, and simple to operate, purify easily, are suitable for industrialization, and can not produce the problem of sulfate radical content reduction.
First, the present invention relates to a kind of preparation method of oligomeric xylose, it comprises the following step:
(1) in the aqueous solution of alkali, xylan hydrogen peroxide is carried out oxidative degradation reaction;
(2), after the reaction of step (1) terminates, regulate reaction solution pH to be 4 ~ 7, in reaction solution, add C
1~ C
4fatty alcohol, separate out white solid, i.e. obtained oligomeric xylose; The weight-average molecular weight of described oligomeric xylose is 2000 ~ 4000;
Wherein, the aqueous solution of alkali is the aqueous solution of alkaline-earth metal and/or alkali-metal oxyhydroxide, and paper mill wastewater is 1mg/ml ~ 40mg/ml; The mass ratio of alkali and xylan is 0.01 ~ 0.4; The mass ratio of hydrogen peroxide and xylan is 0.03: 1 ~ 0.3: 1; Oxidative degradation reaction temperature be 80 DEG C to reflux temperature.
In step (1), in the aqueous solution of described alkali, paper mill wastewater is preferably 10mg/ml ~ 20mg/ml.The temperature of described oxidative degradation reaction be preferably 95 DEG C to reflux temperature.Described C
1~ C
4fatty alcohol be preferably methyl alcohol or ethanol.The mass ratio of hydrogen peroxide and xylan is preferably 0.09: 1 ~ 0.18: 1.Described hydrogen peroxide is the pure hydrogen peroxide in solution, and in general, hydrogen peroxide participates in reaction in form of an aqueous solutions, and its mass concentration is preferably 20% ~ 40%, and better is 30%.In the aqueous solution of described alkali, described alkaline-earth metal and/or alkali-metal oxyhydroxide are preferably sodium hydroxide and/or potassium hydroxide.The mass ratio of alkali and xylan is preferably 0.1 ~ 0.25.Described xylan can be the xylan of this area routine, and its weight-average molecular weight is preferably 10000 ~ 40000.It is stopped reaction that oxidative degradation reaction is generally 20 minutes ~ 2 hours, confirms product quality by this area ordinary method.
In step (1), preferably, first xylan is added in the aqueous solution of alkali, become partly soluble suspension liquid, add the aqueous hydrogen peroxide solution of mass concentration 20% ~ 40% (preferably 30%), react under 80 DEG C to reflux temperature.
In step (2), preferably, C is being added
1~ C
4fatty alcohol before, first cool, then regulate the pH of reaction solution to be 4 ~ 7 (preferably 4 ~ 6, further preferably 5).The method of the adjustment pH described in step (2) can be the tune pH method of this area routine, regulates as added dilute acid solution.
In step (2), described C
1~ C
4fatty alcohol add volume for till making white solid no longer separate out, be preferably 3 ~ 8 times of reaction solution volume.
The invention further relates to the oligomeric xylose obtained by above-mentioned preparation method.
The invention still further relates to the preparation method that a kind of piperylene gathers sodium sulfate, it comprises the following step: the reaction above-mentioned oligomeric xylose being carried out into sulphonate, and salt-forming reaction.
Wherein, the method of the reaction of described one-tenth sulphonate and condition all can be ordinary method and the condition that piperylene polysulfonates is prepared in this area, the preferred following method of the present invention: under the effect of alkali, above-mentioned oligomeric xylose and chlorsulfonic acid and/or sulfur trioxide pyridine are carried out into the reaction of sulphonate.
Wherein, described alkali is preferably one or more in pyridine, α-methylpyridine, beta-picoline and γ-picoline.The consumption of alkali is preferably 2 ~ 10 times of the quality of oligomeric xylose, preferably 5 ~ 10 times.Described chlorsulfonic acid and/or the consumption of sulfur trioxide pyridine are preferably 3 ~ 6 times of the quality of oligomeric xylose.The temperature of the reaction of described one-tenth sulphonate is preferably 60 ~ 80 DEG C.The reaction of described one-tenth sulphonate, by terminating reaction after the confirmation product quality of this area routine, is generally 2 ~ 24 hours, preferably 3 ~ 10 hours.
In the present invention, the method of described salt-forming reaction and condition all can be this area and prepare piperylene and gather ordinary method in the salt-forming reaction of sodium sulfate and condition, the preferred following method of the present invention: carry out salt-forming reaction by becoming the water-ol mixing solutions of the obtained product alkali of sulphonate reaction, again after dialysis method removing inorganic salt, be concentrated into suitable volumes, crystallization in instillation alcohol, namely obtains the product that weight-average molecular weight is 4000 ~ 6000.Wherein, the alkali in described salt-forming reaction is preferably one or more in sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium bicarbonate and saleratus etc., and better is sodium hydroxide and/or potassium hydroxide.
On the basis meeting this area general knowledge, above-mentioned each optimum condition, can arbitrary combination, obtains the preferred embodiments of the invention.
Agents useful for same of the present invention and raw material are all commercially.
Positive progressive effect of the present invention is: the present invention adopts first oxidative degradation in the basic conditions to become the method for sulfonate to obtain poly-pentose polysulfonates and salt thereof again, can obtain the target product that molecular weight is 4000-6000, avoid complicated method of purification.And the problem that the sulfate radical content produced when it also avoid first sulfonated depolymerization again reduces.And the present invention is easy and simple to handle, with low cost, the needs of suitability for industrialized production can be adapted to.
Embodiment
Mode below by embodiment further illustrates the present invention, but does not therefore limit the present invention among described scope of embodiments.The experimental technique of unreceipted actual conditions in the following example, conventionally and condition, or selects according to catalogue.
In following embodiment:
The authentication method of oligomeric xylose, namely gel filter method can reference: " chemistry of herbal polysaccharide and pharmacology " Ji Yubin work, People's Health Publisher, the method is summarized as follows: use SephadexG-75 post, 0.2M NaCl aqueous solution wash-out, recording oligomeric xylose molecular weight is 2000 ~ 4000.
The weight-average molecular weight of raw material xylan is 30000.
Finally obtained piperylene gathers sodium sulfate and passes through capillary electrophoresis method, fingerprint chromatogram is consistent with standard substance, gel filters method determining molecular weight 4000 ~ 6000, and determination of elemental analysis sulphur content 15 ~ 17.5%, proves that the product obtained is consistent with Elmiron standard substance.Testing and appraisal method reference: Arch.Pharm.Pharm.Med.Chem.2001,334,27-29.
Embodiment 1
10g xylan adds in the aqueous sodium hydroxide solution of 100mL 1mg/mL, and 80 DEG C of stirrings, become suspension liquid; Add 1.5mL 20% superoxol, 80 DEG C are reacted 2 hours; Ice-water bath cools rapidly, regulates pH=4 with 1mol/L hydrochloric acid; Add 300mL methyl alcohol, adularescent solid is separated out.Filter, vacuum-drying, obtains white solid 6.2g.Productive rate 62%, recording oligomeric xylose molecular weight by gel filtration method is 2000 ~ 4000.
25mL pyridine is added in above-mentioned 6.2g white solid; Stir and after being heated to 60 DEG C, 20g sulfur trioxide pyridine slowly added reaction system, simultaneously vigorous stirring; After treating that sulfur trioxide pyridine adds, 60 DEG C are kept to react 2 hours; After completion of the reaction, system poured in 125mL methyl alcohol, vigorous stirring, obtains micro-yellow solid simultaneously; After filtration, filter cake is dissolved in 20mL water, in the mixed solvent of rear instillation 250mL methyl alcohol and 13mL 33% aqueous sodium hydroxide solution, continuously stirring; After completion of the reaction, in system, drip acetic acid to pH=6, obtain white solid; Filter, with methyl alcohol, acetone and ether washing leaching cake respectively; After filter cake is soluble in water, through dialysis membrane process, removing inorganic salt; Be concentrated into 50 milliliters, instill in 150 milliliters of ethanol, collecting by filtration white solid, vacuum-drying, obtains target product 10.3g.Filter method with gel to record piperylene to gather sodium sulfate molecular weight be 4000 ~ 6000, ultimate analysis S content 17.2%.
Embodiment 2
10g xylan adds in the aqueous sodium hydroxide solution of 135mL 15mg/mL, and 80 DEG C of stirrings, become suspension liquid; Add 3.7mL 30% superoxol, back flow reaction 1.5 hours; Ice-water bath cools rapidly, regulates pH=5 with 1mol/L hydrochloric acid; Add 600mL ethanol, adularescent solid is separated out.Filter, vacuum-drying, obtains white solid 7.8g.Productive rate 78%, recording oligomeric xylose molecular weight by gel filtration method is 2000 ~ 4000.
40mL γ-picoline is added in above-mentioned 7.8g white solid; Stir and after being heated to 60 DEG C, 40g sulfur trioxide pyridine slowly added reaction system, simultaneously vigorous stirring; After treating that sulfur trioxide pyridine adds, be warming up to 80 DEG C of reactions 4 hours; After completion of the reaction, system poured in 200mL methyl alcohol, vigorous stirring, obtains micro-yellow solid simultaneously; After filtration, filter cake is dissolved in 30mL water, in the mixed solvent of rear instillation 400mL methyl alcohol and 20mL 33% aqueous sodium hydroxide solution, continuously stirring; After completion of the reaction, in system, drip acetic acid to pH=6, obtain white solid; Filter, with methyl alcohol, acetone and ether washing leaching cake respectively; After filter cake is soluble in water, through dialysis membrane process, removing inorganic salt; Be concentrated into 270 milliliters, instill in 800 milliliters of ethanol, collecting by filtration white solid, vacuum-drying, obtains target product 11.2g.Filter method with gel to record piperylene to gather sodium sulfate molecular weight be 4000 ~ 6000, ultimate analysis S content 16.2%.
Embodiment 3
10g xylan adds in the aqueous sodium hydroxide solution of 50mL 40mg/mL, and 80 DEG C of stirrings, become suspension liquid; Add 9mL 40% superoxol, 95 DEG C are reacted 1.5 hours; Ice-water bath cools rapidly, regulates pH=5 with 1mol/L hydrochloric acid; Add 400mL propyl alcohol, adularescent solid is separated out.Filter, vacuum-drying, obtains white solid 5.3g.Productive rate 53%, recording oligomeric xylose molecular weight by gel filtration method is 2000 ~ 4000.
50mL α-methylpyridine is added in above-mentioned 5.3g white solid; Stir and after being heated to 60 DEG C, 32g sulfur trioxide pyridine slowly added reaction system, simultaneously vigorous stirring; After treating that sulfur trioxide pyridine adds, remain on 60 DEG C of reactions 6 hours; After completion of the reaction, system poured in 270mL methyl alcohol, vigorous stirring, obtains micro-yellow solid simultaneously; After filtration, filter cake is dissolved in 40mL water, in the mixed solvent of rear instillation 500mL methyl alcohol and 25mL 33% aqueous sodium hydroxide solution, continuously stirring; After completion of the reaction, in system, drip acetic acid to pH=6, obtain white solid; Filter, with methyl alcohol, acetone and ether washing leaching cake respectively; After filter cake is soluble in water, through dialysis membrane process, removing inorganic salt; Be concentrated into 270 milliliters, instill in 800 milliliters of ethanol, collecting by filtration white solid, vacuum-drying, obtains target product 8.5g.Filter method with gel to record piperylene to gather sodium sulfate molecular weight be 4000 ~ 6000, ultimate analysis S content 16.4%.
Embodiment 4
10g xylan adds in the aqueous sodium hydroxide solution of 100mL 40mg/mL, and 80 DEG C of stirrings, become suspension liquid; Add 3mL 40% superoxol, keep 80 DEG C to react 20 minutes; Ice-water bath cools rapidly, regulates pH=6 with 1mol/L hydrochloric acid; Add 400mL butanols, adularescent solid is separated out.Filter, vacuum-drying, obtains white solid 7g.Productive rate 70%, recording oligomeric xylose molecular weight by gel filtration method is 2000 ~ 4000.
Measure 21mL chlorsulfonic acid, slowly join in 60mL pyridine, control temperature is below 40 DEG C; After dropwising, system temperature is risen to 60 DEG C, and add above-mentioned obtained 7g product; Finish, be warming up to 80 DEG C of reactions 12 hours; After completion of the reaction, system poured in 280mL methyl alcohol, vigorous stirring, obtains micro-yellow solid simultaneously; After filtration, filter cake is dissolved in 45mL water, in the mixed solvent of rear instillation 560mL methyl alcohol and 30mL 33% aqueous sodium hydroxide solution, continuously stirring; After completion of the reaction, in system, drip acetic acid to pH=6, obtain white solid; Filter, with methyl alcohol, acetone and ether washing leaching cake respectively; After filter cake is soluble in water, through dialysis membrane process, removing inorganic salt; Be concentrated into 120 milliliters, instill in 360 milliliters of ethanol, collecting by filtration white solid, vacuum-drying, obtains target product 9.3g.Recording oligomeric xylose molecular weight by gel filtration method is 4000 ~ 6000, ultimate analysis S content 15.3%.
Embodiment 5
10g xylan adds in the potassium hydroxide aqueous solution of 135mL 15mg/mL, and 80 DEG C of stirrings, become suspension liquid; Add 3.7mL 30% superoxol, back flow reaction 20 minutes; Ice-water bath cools rapidly, regulates pH=4 with 1mol/L hydrochloric acid; Add 500mL methyl alcohol, adularescent solid is separated out.Filter, vacuum-drying, obtains white solid 7.2g.Productive rate 72%, recording oligomeric xylose molecular weight by gel filtration method is 2000 ~ 4000.
15mL pyridine is added in above-mentioned 7.2g white solid; Stir and after being heated to 60 DEG C, 29g sulfur trioxide pyridine slowly added reaction system, simultaneously vigorous stirring; After treating that sulfur trioxide pyridine adds, be warming up to 80 DEG C of reactions 6 hours; After completion of the reaction, system poured in 70mL methyl alcohol, vigorous stirring, obtains micro-yellow solid simultaneously; After filtration, filter cake is dissolved in 12mL water, in the mixed solvent of rear instillation 140mL methyl alcohol and 8mL 33% aqueous sodium hydroxide solution, continuously stirring; After completion of the reaction, in system, drip acetic acid to pH=6, obtain white solid; Filter, with methyl alcohol, acetone and ether washing leaching cake respectively; After filter cake is soluble in water, through dialysis membrane process, removing inorganic salt; Be concentrated into 30 milliliters, instill in 100 milliliters of ethanol, collecting by filtration white solid, vacuum-drying, obtains target product 11.3g.Filter method with gel to record piperylene to gather sodium sulfate molecular weight be 4000 ~ 6000, ultimate analysis S content 17.1%.
Embodiment 6
10g xylan adds in the potassium hydroxide aqueous solution of 135mL 15mg/mL, and 80 DEG C of stirrings, become suspension liquid; Add 11mL 30% superoxol, back flow reaction 20 minutes; Ice-water bath cools rapidly, regulates pH=6 with 1mol/L hydrochloric acid; Add 600mL ethanol, adularescent solid is separated out.Filter, vacuum-drying, obtains white solid 7.6g.Productive rate 76%, recording oligomeric xylose molecular weight by gel filtration method is 2000 ~ 4000.
40mL γ-picoline is added in above-mentioned 7.6g white solid; Stir and after being heated to 60 DEG C, 38g sulfur trioxide pyridine slowly added reaction system, simultaneously vigorous stirring; After treating that sulfur trioxide pyridine adds, maintain 60 DEG C of reactions 12 hours; After completion of the reaction, system poured in 190mL methyl alcohol, vigorous stirring, obtains micro-yellow solid simultaneously; After filtration, filter cake is dissolved in 30mL water, in the mixed solvent of rear instillation 380mL methyl alcohol and 19mL 33% aqueous sodium hydroxide solution, continuously stirring; After completion of the reaction, in system, drip acetic acid to pH=6, obtain white solid; Filter, with methyl alcohol, acetone and ether washing leaching cake respectively; After filter cake is soluble in water, through dialysis membrane process, removing inorganic salt; Be concentrated into 80 milliliters, instill in 240 milliliters of ethanol, collecting by filtration white solid, vacuum-drying, obtains target product 11.9g.Filter method with gel to record piperylene to gather sodium sulfate molecular weight be 4000 ~ 6000, ultimate analysis S content 17.2%.
Embodiment 7
10g xylan adds in the potassium hydroxide aqueous solution of 100mL 40mg/mL, and 80 DEG C of stirrings, become suspension liquid; Add 9mL 40% superoxol, back flow reaction 1.5 hours; Ice-water bath cools rapidly, regulates pH=4 with 1mol/L hydrochloric acid; Add 600mL propyl alcohol, adularescent solid is separated out.Filter, vacuum-drying, obtains white solid 6.3g.Productive rate 63%, recording oligomeric xylose molecular weight by gel filtration method is 2000 ~ 4000.
60mL beta-picoline is added in above-mentioned 6.3g white solid; Stir and after being heated to 60 DEG C, 19g sulfur trioxide pyridine slowly added reaction system, simultaneously vigorous stirring; After treating that sulfur trioxide pyridine adds, be warming up to 80 DEG C of reactions 4 hours; After completion of the reaction, system poured in 320mL methyl alcohol, vigorous stirring, obtains micro-yellow solid simultaneously; After filtration, filter cake is dissolved in 50mL water, in the mixed solvent of rear instillation 630mL methyl alcohol and 32mL 33% aqueous sodium hydroxide solution, continuously stirring; After completion of the reaction, in system, drip acetic acid to pH=6, obtain white solid; Filter, with methyl alcohol, acetone and ether washing leaching cake respectively; After filter cake is soluble in water, through dialysis membrane process, removing inorganic salt; Be concentrated into 120 milliliters, instill in 360 milliliters of ethanol, collecting by filtration white solid, vacuum-drying, obtains target product 9.5g.Filter method with gel to record piperylene to gather sodium sulfate molecular weight be 4000 ~ 6000, ultimate analysis S content 16.5%.
Embodiment 8
10g xylan adds in the potassium hydroxide aqueous solution of 100mL 1mg/mL, and 80 DEG C of stirrings, become suspension liquid; Add 5.3mL 20% superoxol, back flow reaction 2 hours; Ice-water bath cools rapidly, regulates pH=5 with 1mol/L hydrochloric acid; Add 600mL propyl alcohol, adularescent solid is separated out.Filter, vacuum-drying, obtains white solid 6.2g.Productive rate 62%, recording oligomeric xylose molecular weight by gel filtration method is 2000 ~ 4000.
Measure 25mL chlorsulfonic acid, slowly join in 65mL α-methylpyridine, control temperature is below 40 DEG C; After dropwising, system temperature is risen to 60 DEG C, and add above-mentioned obtained 6.2g product; Finish, be warming up to 80 DEG C of reactions 6 hours; After completion of the reaction, system poured in 320mL methyl alcohol, vigorous stirring, obtains micro-yellow solid simultaneously; After filtration, filter cake is dissolved in 50mL water, in the mixed solvent of rear instillation 620mL methyl alcohol and 35mL 33% aqueous sodium hydroxide solution, continuously stirring; After completion of the reaction, in system, drip acetic acid to pH=6, obtain white solid; Filter, with methyl alcohol, acetone and ether washing leaching cake respectively; After filter cake is soluble in water, through dialysis membrane process, removing inorganic salt; Be concentrated into 120 milliliters, instill in 400 milliliters of ethanol, collecting by filtration white solid, vacuum-drying, obtains target product 21g.Recording oligomeric xylose molecular weight by gel filtration method is 4000 ~ 6000, ultimate analysis S content 15.3%.
Embodiment 9
10g xylan adds in the baryta water of 100mL 10mg/mL, and 80 DEG C of stirrings, become suspension liquid; Add 9mL 30% superoxol, back flow reaction 1.5 hours; Ice-water bath cools rapidly, regulates pH=5 with 1mol/L hydrochloric acid; Add 400mL ethanol, adularescent solid is separated out.Filter, vacuum-drying, obtains white solid 6.4g.Productive rate 64%, recording oligomeric xylose molecular weight by gel filtration method is 2000 ~ 4000.
60mL α-methylpyridine is added in above-mentioned 6.4g white solid; Stir and after being heated to 60 DEG C, 20g sulfur trioxide pyridine slowly added reaction system, simultaneously vigorous stirring; After treating that sulfur trioxide pyridine adds, be warming up to 80 DEG C of reactions 4 hours; After completion of the reaction, system poured in 320mL methyl alcohol, vigorous stirring, obtains micro-yellow solid simultaneously; After filtration, filter cake is dissolved in 50mL water, in the mixed solvent of rear instillation 630mL methyl alcohol and 32mL 33% aqueous sodium hydroxide solution, continuously stirring; After completion of the reaction, in system, drip acetic acid to pH=6, obtain white solid; Filter, with methyl alcohol, acetone and ether washing leaching cake respectively; After filter cake is soluble in water, through dialysis membrane process, removing inorganic salt; Be concentrated into 120 milliliters, instill in 360 milliliters of ethanol, collecting by filtration white solid, vacuum-drying, obtains target product 10.4g.Filter method with gel to record piperylene to gather sodium sulfate molecular weight be 4000 ~ 6000, ultimate analysis S content 16.8%.
Claims (14)
1. a preparation method for oligomeric xylose, is characterized in that comprising the following step:
(1) in the aqueous solution of alkali, xylan hydrogen peroxide is carried out oxidative degradation reaction;
(2), after the reaction of step (1) terminates, regulate reaction solution pH to be 4 ~ 7, in reaction solution, add C
1~ C
4fatty alcohol, separate out white solid, i.e. obtained oligomeric xylose; The weight-average molecular weight of described oligomeric xylose is 2000 ~ 4000;
Wherein, the aqueous solution of alkali is the aqueous solution of alkaline-earth metal and/or alkali-metal oxyhydroxide, and paper mill wastewater is 1mg/ml ~ 40mg/ml; The mass ratio of alkali and xylan is 0.01 ~ 0.4; The mass ratio of hydrogen peroxide and xylan is 0.03:1 ~ 0.3:1; Oxidative degradation reaction temperature be 80 DEG C to reflux temperature;
In step (1), first xylan is added in the aqueous solution of alkali, becomes partly soluble suspension liquid, add the aqueous hydrogen peroxide solution of mass concentration 20% ~ 40%, react under 80 DEG C to reflux temperature; In step (1), the described oxidative degradation reaction times is 20 minutes ~ 2 hours; In step (2), described C
1~ C
4fatty alcohol be methyl alcohol or ethanol.
2. preparation method as claimed in claim 1, is characterized in that:
In step (1), in the aqueous solution of described alkali, paper mill wastewater is 10mg/ml ~ 20mg/ml.
3. preparation method as claimed in claim 1, is characterized in that: in step (1), the temperature of described oxidative degradation reaction be 95 DEG C to reflux temperature.
4. preparation method as claimed in claim 1, it is characterized in that: in step (1), described hydrogen peroxide and the mass ratio of xylan are 0.09:1 ~ 0.18:1; Described hydrogen peroxide participates in reaction in form of an aqueous solutions, and the mass concentration of described aqueous hydrogen peroxide solution is 20% ~ 40%.
5. preparation method as claimed in claim 1, it is characterized in that: in step (1), in the aqueous solution of described alkali, described alkaline-earth metal and/or alkali-metal oxyhydroxide are sodium hydroxide and/or potassium hydroxide.
6. preparation method as claimed in claim 1, it is characterized in that: in step (1), described alkali and the mass ratio of xylan are 0.1 ~ 0.25.
7. preparation method as claimed in claim 1, it is characterized in that: in step (1), the weight-average molecular weight of described xylan is 10000 ~ 40000.
8. preparation method as claimed in claim 1, is characterized in that: in step (2), adding C
1~ C
4fatty alcohol before, first cool, then regulate the pH of reaction solution to be 4 ~ 6.
9. preparation method as claimed in claim 1, is characterized in that: in step (2), described C
1~ C
4fatty alcohol add 3 ~ 8 times that volume is reaction solution volume.
10. the oligomeric xylose that the preparation method as described in any one of claim 1 ~ 9 obtains.
11. 1 kinds of piperylenes gather the preparation method of sodium sulfate, it is characterized in that comprising the following step: reaction oligomeric xylose according to claim 10 being carried out into sulphonate, and salt-forming reaction.
12. preparation methods as claimed in claim 11, it is characterized in that: the reaction of described one-tenth sulphonate comprises the following step: under the effect of alkali, oligomeric xylose according to claim 13 and chlorsulfonic acid and/or sulfur trioxide pyridine are carried out into the reaction of sulphonate.
13. preparation methods as claimed in claim 12, is characterized in that: described alkali is one or more in pyridine, α-methylpyridine, beta-picoline and γ-picoline; The consumption of alkali is 2 ~ 10 times of the quality of oligomeric xylose; Described chlorsulfonic acid and/or the consumption of sulfur trioxide pyridine are 3 ~ 6 times of the quality of oligomeric xylose; The temperature of the reaction of described one-tenth sulphonate is 60 ~ 80 DEG C; The time of the reaction of described one-tenth sulphonate is 2 ~ 24 hours.
14. preparation methods as claimed in claim 11, it is characterized in that: described salt-forming reaction comprises the following step: carry out salt-forming reaction by becoming the water-ol mixing solutions of the obtained product alkali of sulphonate reaction, again after dialysis method removing inorganic salt, concentrated, crystallization in instillation alcohol, namely obtains the product that weight-average molecular weight is 4000 ~ 6000.
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| CN103130917A (en) * | 2013-03-21 | 2013-06-05 | 苏州鸿洋医药科技有限公司 | Preparation method of pentosan polysulfuric acid and salt thereof |
| CN105037586A (en) * | 2015-06-08 | 2015-11-11 | 同济大学 | Anticoagulant medical material and preparation method thereof |
| MX2020002288A (en) | 2016-08-31 | 2020-07-14 | Oji Holdings Corp | Production method for acidic xylooligosaccharide, and acidic xylooligosaccharide. |
| JP6225321B1 (en) | 2016-08-31 | 2017-11-08 | 王子ホールディングス株式会社 | Method for producing polysulfate pentosan |
| JP6281659B1 (en) * | 2017-02-28 | 2018-02-21 | 王子ホールディングス株式会社 | Polysulfate pentosan, pharmaceutical composition and anticoagulant |
| JP6555431B2 (en) * | 2017-05-31 | 2019-08-07 | 王子ホールディングス株式会社 | Moisturizing topical agent |
| WO2019054344A1 (en) | 2017-09-12 | 2019-03-21 | 王子ホールディングス株式会社 | Pentosan polysulfate and method for producing pentosan polysulfate |
| PT3730521T (en) | 2017-12-20 | 2023-06-19 | Oji Holdings Corp | Pentosan polysulfate and medicine containing pentosan polysulfate |
| CN117624404B (en) * | 2024-01-25 | 2024-03-29 | 默普生物科技(山东)有限公司 | Synthetic process for improving chemical stability and biological activity of dextran sodium sulfate |
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| CN1431231A (en) * | 2003-01-29 | 2003-07-23 | 广西壮族自治区中国科学院广西植物研究所 | Method for extracting xylan from woody fiber material |
| CN1847254B (en) * | 2005-08-30 | 2010-05-05 | 南京林业大学 | Preparation and separation process of components for xylose oligomer of polymerization degree 2-8 |
| WO2009087581A1 (en) * | 2008-01-04 | 2009-07-16 | Alembic Limited | An improved process for the preparation of pentosan polysulfate or salts thereof |
| CN101736057A (en) * | 2008-11-06 | 2010-06-16 | 上海市农业科学院 | Method for preparing lower polyxylose with bamboo wood scrap material |
| WO2012101544A1 (en) * | 2011-01-29 | 2012-08-02 | Alembic Pharmaceuticals Limited | An improved process for the preparation of pentosan polysulfate or salts thereof |
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