CN102766225A - Preparation method of peritosan polysulfate sodium and xylooligosaccharide - Google Patents
Preparation method of peritosan polysulfate sodium and xylooligosaccharide Download PDFInfo
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Abstract
The invention discloses a preparation method of xylooligosaccharide, comprising the following steps of: (1) carrying out oxidative degradation reaction on xylan by the use of hydrogen peroxide in an alkaline aqueous solution; And (2) adjusting pH of the reaction solution to 4-7 after the reaction is finished in the step (1), adding C1-C4 fatty alcohol into the reaction solution, and precipitating a while solid, so as to prepare xylooligosaccharide with its weight average molecular weight being 2000-4000, wherein the alkaline aqueous solution is an aqueous solution of alkaline earth metal and/or hydroxides of alkali metal, and the concentration of alkali is 1mg/ml-40mg/ml; the mass ratio of alkali to xylan is 0.01-0.4; the mass ratio of hydrogen peroxide to xylan is 0.03:1-0.3:1; and the temperature for the oxidative degradation reaction is 80 DEG C to reflux temperature. Different from the prior art, the preparation method provided by the invention is simple to operate and is suitable for industrialization. By the adoption of the preparation method, it is easy to purify, and the content of sulfate radical will not be reduced.
Description
Technical field
A kind of piperylene that relates to that the present invention is concrete gathers Preparation of sodium method 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); It is a kind of medicine of treating kidney infection, interstitial cystitis and tumour; Produced by Ortho McNeil company, commodity
this product by name does not go on the market in the China's Mainland as yet.
Structural formula 2
It is a kind of semi-synthetic heparin class macromole glucide that piperylene gathers sodium sulfate, is the tasteless powder of a kind of white, and faint water absorbability is arranged, can be water-soluble.
It is to be raw material with xylan (can from bark, extract) that known piperylene gathers sodium sulfate, and through FOUR EASY STEPS: the first step becomes sulfuric ester, second to go on foot into sodium salt, the 3rd step depolymerization, the 4th step separation and purification to get.
Patent US2689848 mentions, and xylan is through following FOUR EASY STEPS: under the participation at pyridine of the first step and chlorsulfonic acid, make the xylan sulfuric ester; Second step and sodium hydroxide react under the methanol-water mixed solvent, make xylan and gather sodium sulfate; In the 3rd step, oxidation depolymerization in the acidity or the neutral aqueous solution makes depolymerization product; In the 4th step, depolymerization product is through the dialysis method desalination, and class settling filters the title product that obtains mentioning in the patent.Title 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 title product, but also has following shortcoming: 1, complex operation, and cost is high, and productive rate is low; 2, second go on foot into sodium salt after, the product thickness that obtains, inconvenient filter operation; 3, the 4th step was used dialysis membrane during purifying, can't adapt to suitability for industrialized production.
Patent WO2009/087581 optimizes said process: in the sulfation of the first step wood sugar, use skin Courlene (having used α, β, γ-picoline respectively) to substitute pyridine, improved yield; Go on foot in the process of sodium salt second, use pure methyl alcohol, reduce post-processing difficulty as solvent; In the 4th step separation and purification, use the nf membrane system to obtain the product of molecular weight as 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 be through more loaded down with trivial details purification means, and like the method for US2689848 employing class settling, WO2009/087581 adopts the nf membrane system.2, the operation of oxidation depolymerization all is to gather the sodium sulfate stage at piperylene to carry out, because sulfate radical is unstable, is prone to the engaging sulphate side reaction takes place the problem that causes degree to descend.Too much influence drug effect for avoiding degree to descend, the depolymerization time must strict control, and this causes the polysaccharide chains degraded incomplete, makes that molecular weight is that the title product productive rate of 4000-6000 is low excessively.(productive rate of US2689848 depolymerization step is all less than 50%, and the productive rate of WO2009/087581 depolymerization step is all less than 55%).
Summary of the invention
Technical problem to be solved by this invention is to gather in the Preparation of sodium method in order to overcome existing piperylene; Complex operation, cost is high, and productive rate is low; Defective such as sulfate radical content reduction during depolymerization, and provide a kind of piperylene to gather Preparation of sodium method and a kind of oligomeric xylose.The present invention directly carries out the oxidation depolymerization to xylan, owing to there is not side reaction such as engaging sulphate, can realize controlled and sufficient depolymerization; Thereby obtain high yield, even molecular weight distribution and the oligomeric xylose that meets the requirements; Then it is carried out sulfation, obtain title product.Therefore preparation method of the present invention is different fully with prior art, and simple to operate, purifies easily, is suitable for industriallization, and can not produce the problem that sulfate radical content reduces.
At 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 is carried out the oxidation depolymerization reaction with hydrogen peroxide;
(2) after the reaction of step (1) finished, conditioned reaction liquid pH was 4～7, in reaction solution, adds C
1～C
4Fatty Alcohol(C12-C14 and C12-C18), separate out white solid, promptly make 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 earth alkali metal and/or alkali-metal oxyhydroxide, and the concentration of alkali 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; The temperature of oxidation depolymerization reaction be 80 ℃ to reflux temperature.
In the step (1), in the aqueous solution of described alkali, that the concentration of alkali is preferable is 10mg/ml～20mg/ml.The temperature of described oxidation depolymerization reaction is preferable be 95 ℃ to reflux temperature.Described C
1～C
4Fatty Alcohol(C12-C14 and C12-C18) preferable be methyl alcohol or ethanol.What the mass ratio of hydrogen peroxide and xylan was preferable is 0.09: 1～0.18: 1.Described hydrogen peroxide is the pure hydrogen peroxide in the solution, and in general, hydrogen peroxide is participated in reaction with the form of the aqueous solution, and what its mass concentration was preferable is 20%～40%, and better is 30%.In the aqueous solution of described alkali, what described earth alkali metal and/or alkali-metal oxyhydroxide were preferable is sodium hydroxide and/or Pottasium Hydroxide.What the mass ratio of alkali and xylan was preferable is 0.1～0.25.Described xylan can be the conventional xylan in this area, and what its weight-average molecular weight was preferable is 10000～40000.It is stopped reaction that the oxidation depolymerization reaction is generally 20 minutes～2 hours, confirms product quality through this area ordinary method.
In the step (1), preferable, earlier 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% (preferred 30%), react to reflux temperature at 80 ℃, get final product.
In the step (2), preferable, adding C
1～C
4Fatty Alcohol(C12-C14 and C12-C18) before, cooling earlier, the pH of re-adjustment reaction solution is 4～7 (preferred 4～6, further preferred 5).The method of adjusting pH described in the step (2) can be the conventional accent pH method in this area, regulates as adding dilute acid solution.
In the step (2), described C
1～C
4The adding volume of Fatty Alcohol(C12-C14 and C12-C18) for till making white solid and no longer separating out, 3～8 times of preferable is reaction solution volume.
The invention further relates to the oligomeric xylose that makes by above-mentioned preparation method.
The invention still further relates to a kind of piperylene and gather the Preparation of sodium method, it comprises the following step: above-mentioned oligomeric xylose is carried out to the reaction of sulphonate, and salt-forming reaction, get final product.
Wherein, The method of the reaction of described one-tenth sulphonate and condition all can be ordinary method and the condition that this area prepares the piperylene polysulfonates; The preferred following method of the present invention: under the effect of alkali; Above-mentioned oligomeric xylose and chlorsulfonic acid and/or sulphur trioxide pyridine are carried out to the reaction of sulphonate, get final product.
Wherein, described alkali is preferable is in pyridine, α-Jia Jibiding, beta-picoline and the γ-picoline one or more.The consumption of alkali is preferable is 2～10 times of quality of oligomeric xylose, preferred 5～10 times.The consumption of described chlorsulfonic acid and/or sulphur trioxide pyridine is preferable is 3～6 times of quality of oligomeric xylose.What the temperature of the reaction of described one-tenth sulphonate was preferable is 60～80 ℃.The reaction of described one-tenth sulphonate can be generally preferred 3～10 hours 2～24 hours through finishing reaction after the conventional affirmation product quality in this area.
Among the present invention; The method of described salt-forming reaction and condition all can be this area and prepare piperylene and gather ordinary method and condition in the salt-forming reaction of sodium sulfate; The preferred following method of the present invention: will become product that sulphonate reaction makes to be carried out to reactant salt, and after dialysis method is removed inorganic salt, be concentrated into suitable volumes again with the water-mixed alkoxide solution of alkali; Splash in the alcohol crystallization and separate out, promptly obtain weight-average molecular weight and be 4000～6000 product.Wherein, the alkali in the described salt-forming reaction is preferable is in sodium hydroxide, Pottasium Hydroxide, yellow soda ash, salt of wormwood, sodium hydrogencarbonate and the saleratus etc. one or more, and better is sodium hydroxide and/or Pottasium Hydroxide.
On the basis that meets this area general knowledge, above-mentioned each optimum condition, but arbitrary combination promptly get each preferred embodiments of the present invention.
Agents useful for same of the present invention and raw material are all commercially available to be got.
Positive progressive effect of the present invention is: the present invention adopts elder generation's oxidation depolymerization under alkaline condition to become the method for sulphonate to make poly-pentose polysulfonates and salt thereof again, can obtain the title product that molecular weight is 4000-6000, has avoided complicated method of purification.And the problem that reduces of the sulfate radical content that produces when having avoided first sulfonated depolymerization again.And the present invention is easy and simple to handle, and is with low cost, can adapt to need of industrial production.
Embodiment
Mode through embodiment further specifies the present invention below, but does not therefore limit the present invention among the described scope of embodiments.The experimental technique of unreceipted actual conditions in the following example according to ordinary method and condition, or is selected according to catalogue.
Below among each embodiment:
The authentication method of oligomeric xylose; Be but that gel filters the method reference: " chemistry of herbal polysaccharide and pharmacology " Ji Yubin work, the People's Health Publisher, this method is summarized as follows: use the SephadexG-75 post; 0.2M NaCl aqueous solution wash-out, recording the oligomeric xylose molecular weight is 2000～4000.
The weight-average molecular weight of raw material xylan is 30000.
The piperylene that makes at last gathers sodium sulfate and passes through capillary electrophoresis method; The fingerprint spectrogram is consistent with standard substance; Gel filters the method determining molecular weight 4000～6000, and determination of elemental analysis sulphur content 15～17.5% proves that the product that obtains is consistent with the Elmiron standard substance.Detect the authentication method reference: Arch.Pharm.Pharm.Med.Chem.2001,334,27-29.
Embodiment 1
The 10g xylan adds in the aqueous sodium hydroxide solution of 100mL 1mg/mL, and 80 ℃ of stirrings become suspension liquid; Add 1.5mL 20% superoxol, 80 ℃ were reacted 2 hours; Ice-water bath cools off rapidly, regulates pH=4 with 1mol/L hydrochloric acid; Add 300mL methyl alcohol, the adularescent solid is separated out.Filter, vacuum-drying gets white solid 6.2g.Productive rate 62%, using gel filtration method to record the oligomeric xylose molecular weight is 2000～4000.
In above-mentioned 6.2g white solid, add the 25mL pyridine; After stirring and being heated to 60 ℃, 20g sulphur trioxide pyridine is slowly added reaction system, simultaneously vigorous stirring; After treating that the adding of sulphur trioxide pyridine finishes, keep 60 ℃ of reactions 2 hours; After reaction finishes, system is poured in the 125mL methyl alcohol, vigorous stirring obtains little yellow solid simultaneously; After the filtration, filter cake is dissolved in the 20mL water, after splash in the mixed solvent of 250mL methyl alcohol and 13mL 33% aqueous sodium hydroxide solution continuously stirring; After reaction finishes, in system, drip acetic acid, obtain white solid to pH=6; Filter, with methyl alcohol, acetone and ether difference washing leaching cake; After filter cake is soluble in water, handle through dialysis membrane, remove inorganic salt; Be concentrated into 50 milliliters, splash in 150 milliliters of ethanol, filter and collect white solid, vacuum-drying obtains title product 10.3g.Using gel filtration method to record piperylene, to gather the sodium sulfate molecular weight be 4000～6000, ultimate analysis S content 17.2%.
Embodiment 2
The 10g xylan adds in the aqueous sodium hydroxide solution of 135mL 15mg/mL, and 80 ℃ of stirrings become suspension liquid; Add 3.7mL 30% superoxol, back flow reaction 1.5 hours; Ice-water bath cools off rapidly, regulates pH=5 with 1mol/L hydrochloric acid; Add 600mL ethanol, the adularescent solid is separated out.Filter, vacuum-drying gets white solid 7.8g.Productive rate 78%, using gel filtration method to record the oligomeric xylose molecular weight is 2000～4000.
In above-mentioned 7.8g white solid, add 40mL γ-picoline; After stirring and being heated to 60 ℃, 40g sulphur trioxide pyridine is slowly added reaction system, simultaneously vigorous stirring; After treating that the adding of sulphur trioxide pyridine finishes, be warming up to 80 ℃ of reactions 4 hours; After reaction finishes, system is poured in the 200mL methyl alcohol, vigorous stirring obtains little yellow solid simultaneously; After the filtration, filter cake is dissolved in the 30mL water, after splash in the mixed solvent of 400mL methyl alcohol and 20mL 33% aqueous sodium hydroxide solution continuously stirring; After reaction finishes, in system, drip acetic acid, obtain white solid to pH=6; Filter, with methyl alcohol, acetone and ether difference washing leaching cake; After filter cake is soluble in water, handle through dialysis membrane, remove inorganic salt; Be concentrated into 270 milliliters, splash in 800 milliliters of ethanol, filter and collect white solid, vacuum-drying obtains title product 11.2g.Using gel filtration method to record piperylene, to gather the sodium sulfate molecular weight be 4000～6000, ultimate analysis S content 16.2%.
Embodiment 3
The 10g xylan adds in the aqueous sodium hydroxide solution of 50mL 40mg/mL, and 80 ℃ of stirrings become suspension liquid; Add 9mL 40% superoxol, 95 ℃ were reacted 1.5 hours; Ice-water bath cools off rapidly, regulates pH=5 with 1mol/L hydrochloric acid; Add the 400mL propyl alcohol, the adularescent solid is separated out.Filter, vacuum-drying gets white solid 5.3g.Productive rate 53%, using gel filtration method to record the oligomeric xylose molecular weight is 2000～4000.
In above-mentioned 5.3g white solid, add the 50mL α-Jia Jibiding; After stirring and being heated to 60 ℃, 32g sulphur trioxide pyridine is slowly added reaction system, simultaneously vigorous stirring; After treating that the adding of sulphur trioxide pyridine finishes, remain on 60 ℃ of reactions 6 hours; After reaction finishes, system is poured in the 270mL methyl alcohol, vigorous stirring obtains little yellow solid simultaneously; After the filtration, filter cake is dissolved in the 40mL water, after splash in the mixed solvent of 500mL methyl alcohol and 25mL 33% aqueous sodium hydroxide solution continuously stirring; After reaction finishes, in system, drip acetic acid, obtain white solid to pH=6; Filter, with methyl alcohol, acetone and ether difference washing leaching cake; After filter cake is soluble in water, handle through dialysis membrane, remove inorganic salt; Be concentrated into 270 milliliters, splash in 800 milliliters of ethanol, filter and collect white solid, vacuum-drying obtains title product 8.5g.Using gel filtration method to record piperylene, to gather the sodium sulfate molecular weight be 4000～6000, ultimate analysis S content 16.4%.
Embodiment 4
The 10g xylan adds in the aqueous sodium hydroxide solution of 100mL 40mg/mL, and 80 ℃ of stirrings become suspension liquid; Add 3mL 40% superoxol, keep 80 ℃ of reactions 20 minutes; Ice-water bath cools off rapidly, regulates pH=6 with 1mol/L hydrochloric acid; Add the 400mL butanols, the adularescent solid is separated out.Filter, vacuum-drying gets white solid 7g.Productive rate 70%, using gel filtration method to record the oligomeric xylose molecular weight is 2000～4000.
Measure the 21mL chlorsulfonic acid, slowly join in the 60mL pyridine, controlled temperature is below 40 ℃; After dropwising, system temperature is risen to 60 ℃, and add the above-mentioned 7g product that makes; Finish, be warming up to 80 ℃ of reactions 12 hours; After reaction finishes, system is poured in the 280mL methyl alcohol, vigorous stirring obtains little yellow solid simultaneously; After the filtration, filter cake is dissolved in the 45mL water, after splash in the mixed solvent of 560mL methyl alcohol and 30mL 33% aqueous sodium hydroxide solution continuously stirring; After reaction finishes, in system, drip acetic acid, obtain white solid to pH=6; Filter, with methyl alcohol, acetone and ether difference washing leaching cake; After filter cake is soluble in water, handle through dialysis membrane, remove inorganic salt; Be concentrated into 120 milliliters, splash in 360 milliliters of ethanol, filter and collect white solid, vacuum-drying obtains title product 9.3g.Using gel filtration method to record the oligomeric xylose molecular weight is 4000～6000, ultimate analysis S content 15.3%.
Embodiment 5
The 10g xylan adds in the potassium hydroxide aqueous solution of 135mL 15mg/mL, and 80 ℃ of stirrings become suspension liquid; Add 3.7mL 30% superoxol, back flow reaction 20 minutes; Ice-water bath cools off rapidly, regulates pH=4 with 1mol/L hydrochloric acid; Add 500mL methyl alcohol, the adularescent solid is separated out.Filter, vacuum-drying gets white solid 7.2g.Productive rate 72%, using gel filtration method to record the oligomeric xylose molecular weight is 2000～4000.
In above-mentioned 7.2g white solid, add the 15mL pyridine; After stirring and being heated to 60 ℃, 29g sulphur trioxide pyridine is slowly added reaction system, simultaneously vigorous stirring; After treating that the adding of sulphur trioxide pyridine finishes, be warming up to 80 ℃ of reactions 6 hours; After reaction finishes, system is poured in the 70mL methyl alcohol, vigorous stirring obtains little yellow solid simultaneously; After the filtration, filter cake is dissolved in the 12mL water, after splash in the mixed solvent of 140mL methyl alcohol and 8mL 33% aqueous sodium hydroxide solution continuously stirring; After reaction finishes, in system, drip acetic acid, obtain white solid to pH=6; Filter, with methyl alcohol, acetone and ether difference washing leaching cake; After filter cake is soluble in water, handle through dialysis membrane, remove inorganic salt; Be concentrated into 30 milliliters, splash in 100 milliliters of ethanol, filter and collect white solid, vacuum-drying obtains title product 11.3g.Using gel filtration method to record piperylene, to gather the sodium sulfate molecular weight be 4000～6000, ultimate analysis S content 17.1%.
Embodiment 6
The 10g xylan adds in the potassium hydroxide aqueous solution of 135mL 15mg/mL, and 80 ℃ of stirrings become suspension liquid; Add 11mL 30% superoxol, back flow reaction 20 minutes; Ice-water bath cools off rapidly, regulates pH=6 with 1mol/L hydrochloric acid; Add 600mL ethanol, the adularescent solid is separated out.Filter, vacuum-drying gets white solid 7.6g.Productive rate 76%, using gel filtration method to record the oligomeric xylose molecular weight is 2000～4000.
In above-mentioned 7.6g white solid, add 40mL γ-picoline; After stirring and being heated to 60 ℃, 38g sulphur trioxide pyridine is slowly added reaction system, simultaneously vigorous stirring; After treating that the adding of sulphur trioxide pyridine finishes, maintain 60 ℃ of reactions 12 hours; After reaction finishes, system is poured in the 190mL methyl alcohol, vigorous stirring obtains little yellow solid simultaneously; After the filtration, filter cake is dissolved in the 30mL water, after splash in the mixed solvent of 380mL methyl alcohol and 19mL 33% aqueous sodium hydroxide solution continuously stirring; After reaction finishes, in system, drip acetic acid, obtain white solid to pH=6; Filter, with methyl alcohol, acetone and ether difference washing leaching cake; After filter cake is soluble in water, handle through dialysis membrane, remove inorganic salt; Be concentrated into 80 milliliters, splash in 240 milliliters of ethanol, filter and collect white solid, vacuum-drying obtains title product 11.9g.Using gel filtration method to record piperylene, to gather the sodium sulfate molecular weight be 4000～6000, ultimate analysis S content 17.2%.
Embodiment 7
The 10g xylan adds in the potassium hydroxide aqueous solution of 100mL 40mg/mL, and 80 ℃ of stirrings become suspension liquid; Add 9mL 40% superoxol, back flow reaction 1.5 hours; Ice-water bath cools off rapidly, regulates pH=4 with 1mol/L hydrochloric acid; Add the 600mL propyl alcohol, the adularescent solid is separated out.Filter, vacuum-drying gets white solid 6.3g.Productive rate 63%, using gel filtration method to record the oligomeric xylose molecular weight is 2000～4000.
In above-mentioned 6.3g white solid, add the 60mL beta-picoline; After stirring and being heated to 60 ℃, 19g sulphur trioxide pyridine is slowly added reaction system, simultaneously vigorous stirring; After treating that the adding of sulphur trioxide pyridine finishes, be warming up to 80 ℃ of reactions 4 hours; After reaction finishes, system is poured in the 320mL methyl alcohol, vigorous stirring obtains little yellow solid simultaneously; After the filtration, filter cake is dissolved in the 50mL water, after splash in the mixed solvent of 630mL methyl alcohol and 32mL 33% aqueous sodium hydroxide solution continuously stirring; After reaction finishes, in system, drip acetic acid, obtain white solid to pH=6; Filter, with methyl alcohol, acetone and ether difference washing leaching cake; After filter cake is soluble in water, handle through dialysis membrane, remove inorganic salt; Be concentrated into 120 milliliters, splash in 360 milliliters of ethanol, filter and collect white solid, vacuum-drying obtains title product 9.5g.Using gel filtration method to record piperylene, to gather the sodium sulfate molecular weight be 4000～6000, ultimate analysis S content 16.5%.
Embodiment 8
The 10g xylan adds in the potassium hydroxide aqueous solution of 100mL 1mg/mL, and 80 ℃ of stirrings become suspension liquid; Add 5.3mL 20% superoxol, back flow reaction 2 hours; Ice-water bath cools off rapidly, regulates pH=5 with 1mol/L hydrochloric acid; Add the 600mL propyl alcohol, the adularescent solid is separated out.Filter, vacuum-drying gets white solid 6.2g.Productive rate 62%, using gel filtration method to record the oligomeric xylose molecular weight is 2000～4000.
Measure the 25mL chlorsulfonic acid, slowly join in the 65mL α-Jia Jibiding, controlled temperature is below 40 ℃; After dropwising, system temperature is risen to 60 ℃, and add the above-mentioned 6.2g product that makes; Finish, be warming up to 80 ℃ of reactions 6 hours; After reaction finishes, system is poured in the 320mL methyl alcohol, vigorous stirring obtains little yellow solid simultaneously; After the filtration, filter cake is dissolved in the 50mL water, after splash in the mixed solvent of 620mL methyl alcohol and 35mL 33% aqueous sodium hydroxide solution continuously stirring; After reaction finishes, in system, drip acetic acid, obtain white solid to pH=6; Filter, with methyl alcohol, acetone and ether difference washing leaching cake; After filter cake is soluble in water, handle through dialysis membrane, remove inorganic salt; Be concentrated into 120 milliliters, splash in 400 milliliters of ethanol, filter and collect white solid, vacuum-drying obtains title product 21g.Using gel filtration method to record the oligomeric xylose molecular weight is 4000～6000, ultimate analysis S content 15.3%.
Embodiment 9
The 10g xylan adds in the baryta water of 100mL 10mg/mL, and 80 ℃ of stirrings become suspension liquid; Add 9mL 30% superoxol, back flow reaction 1.5 hours; Ice-water bath cools off rapidly, regulates pH=5 with 1mol/L hydrochloric acid; Add 400mL ethanol, the adularescent solid is separated out.Filter, vacuum-drying gets white solid 6.4g.Productive rate 64%, using gel filtration method to record the oligomeric xylose molecular weight is 2000～4000.
In above-mentioned 6.4g white solid, add the 60mL α-Jia Jibiding; After stirring and being heated to 60 ℃, 20g sulphur trioxide pyridine is slowly added reaction system, simultaneously vigorous stirring; After treating that the adding of sulphur trioxide pyridine finishes, be warming up to 80 ℃ of reactions 4 hours; After reaction finishes, system is poured in the 320mL methyl alcohol, vigorous stirring obtains little yellow solid simultaneously; After the filtration, filter cake is dissolved in the 50mL water, after splash in the mixed solvent of 630mL methyl alcohol and 32mL 33% aqueous sodium hydroxide solution continuously stirring; After reaction finishes, in system, drip acetic acid, obtain white solid to pH=6; Filter, with methyl alcohol, acetone and ether difference washing leaching cake; After filter cake is soluble in water, handle through dialysis membrane, remove inorganic salt; Be concentrated into 120 milliliters, splash in 360 milliliters of ethanol, filter and collect white solid, vacuum-drying obtains title product 10.4g.Using gel filtration method to record piperylene, to gather the sodium sulfate molecular weight be 4000～6000, ultimate analysis S content 16.8%.
Claims (17)
1. the preparation method of an oligomeric xylose is characterized in that comprising the following step:
(1) in the aqueous solution of alkali, xylan is carried out the oxidation depolymerization reaction with hydrogen peroxide;
(2) after the reaction of step (1) finished, conditioned reaction liquid pH was 4～7, in reaction solution, adds C
1～C
4Fatty Alcohol(C12-C14 and C12-C18), separate out white solid, promptly make 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 earth alkali metal and/or alkali-metal oxyhydroxide, and the concentration of alkali 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; The temperature of oxidation depolymerization reaction be 80 ℃ to reflux temperature.
2. preparation method as claimed in claim 1 is characterized in that:
In the step (1), in the aqueous solution of described alkali, the concentration of alkali is 10mg/ml～20mg/ml.
3. preparation method as claimed in claim 1 is characterized in that: in the step (1), the temperature of described oxidation depolymerization reaction be 95 ℃ to reflux temperature.
4. preparation method as claimed in claim 1 is characterized in that: in the step (1), and described C
1～C
4Fatty Alcohol(C12-C14 and C12-C18) be methyl alcohol or ethanol.
5. preparation method as claimed in claim 1 is characterized in that: in the step (1), the mass ratio of described hydrogen peroxide and xylan is 0.09: 1～0.18: 1; Described hydrogen peroxide is participated in reaction with the form of the aqueous solution, and the mass concentration of described aqueous hydrogen peroxide solution is 20%～40%.
6. preparation method as claimed in claim 1 is characterized in that: in the step (1), in the aqueous solution of described alkali, described earth alkali metal and/or alkali-metal oxyhydroxide are sodium hydroxide and/or Pottasium Hydroxide.
7. preparation method as claimed in claim 1 is characterized in that: in the step (1), the mass ratio of described alkali and xylan is 0.1～0.25.
8. preparation method as claimed in claim 1 is characterized in that: in the step (1), the weight-average molecular weight of described xylan is 10000～40000.
9. preparation method as claimed in claim 1 is characterized in that: the described oxidation depolymerization reaction time is 20 minutes～2 hours.
10. preparation method as claimed in claim 1 is characterized in that: in the step (1), earlier 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%, to reflux temperature, react, get final product at 80 ℃.
11. preparation method as claimed in claim 1 is characterized in that: in the step (2), adding C
1～C
4Fatty Alcohol(C12-C14 and C12-C18) before, cooling earlier, the pH of re-adjustment reaction solution is 4～6.
12. preparation method as claimed in claim 1 is characterized in that: in the step (2), described C
1～C
4The adding volume of Fatty Alcohol(C12-C14 and C12-C18) be 3～8 times of reaction solution volume.
13. the oligomeric xylose that makes like each described preparation method of claim 1～12.
14. a piperylene gathers the Preparation of sodium method, it is characterized in that comprising the following step: the described oligomeric xylose of claim 13 is carried out to the reaction of sulphonate, and salt-forming reaction, get final product.
15. preparation method as claimed in claim 14; It is characterized in that: the reaction of described one-tenth sulphonate comprises the following step: under the effect of alkali; The described oligomeric xylose of claim 13 and chlorsulfonic acid and/or sulphur trioxide pyridine are carried out to the reaction of sulphonate, get final product.
16. preparation method as claimed in claim 15 is characterized in that: described alkali is one or more in pyridine, α-Jia Jibiding, beta-picoline and the γ-picoline; The consumption of alkali is 2～10 times of quality of oligomeric xylose; The consumption of described chlorsulfonic acid and/or sulphur trioxide pyridine is 3～6 times of quality of oligomeric xylose; The temperature of the reaction of described one-tenth sulphonate is 60～80 ℃; The time of the reaction of described one-tenth sulphonate is 2～24 hours.
17. preparation method as claimed in claim 14; It is characterized in that: described salt-forming reaction comprises the following step: will become product that sulphonate reaction makes to be carried out to reactant salt with the water-mixed alkoxide solution of alkali; Again after dialysis method is removed inorganic salt; Concentrate, splash in the alcohol crystallization and separate out, promptly obtain weight-average molecular weight and be 4000～6000 product.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110117390.7A CN102766225B (en) | 2011-05-06 | 2011-05-06 | A kind of piperylene gathers the preparation method of sodium sulfate and a kind of oligomeric xylose |
Applications Claiming Priority (1)
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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 |
| CN110678189A (en) * | 2017-05-31 | 2020-01-10 | 王子控股株式会社 | Moisture-retaining external preparation |
| US11274165B2 (en) * | 2017-02-28 | 2022-03-15 | Oji Holdings Corporation | Pentosan polysulfate, pharmaceutical composition, and anticoagulant |
| US11286272B2 (en) | 2016-08-31 | 2022-03-29 | Oji Holdings Corporation | Production method for acidic xylooligosaccharide, and acidic xylooligosaccharide |
| US11312790B2 (en) | 2016-08-31 | 2022-04-26 | Oji Holdings Corporation | Production method for pentosan polysulfate |
| US11344570B2 (en) | 2017-12-20 | 2022-05-31 | Oji Holdings Corporation | Pentosan polysulfate and medicine containing pentosan polysulfate |
| US11390693B2 (en) | 2017-09-12 | 2022-07-19 | Oji Holdings Corporation | Pentosan polysulfate and method for producing pentosan polysulfate |
| CN117624404A (en) * | 2024-01-25 | 2024-03-01 | 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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| 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 |
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| US11286272B2 (en) | 2016-08-31 | 2022-03-29 | Oji Holdings Corporation | Production method for acidic xylooligosaccharide, and acidic xylooligosaccharide |
| US11312790B2 (en) | 2016-08-31 | 2022-04-26 | Oji Holdings Corporation | Production method for pentosan polysulfate |
| US11274165B2 (en) * | 2017-02-28 | 2022-03-15 | Oji Holdings Corporation | Pentosan polysulfate, pharmaceutical composition, and anticoagulant |
| CN110678189A (en) * | 2017-05-31 | 2020-01-10 | 王子控股株式会社 | Moisture-retaining external preparation |
| US11278485B2 (en) | 2017-05-31 | 2022-03-22 | Oji Holdings Corporation | Moisturizing topical preparation |
| US11390693B2 (en) | 2017-09-12 | 2022-07-19 | Oji Holdings Corporation | Pentosan polysulfate and method for producing pentosan polysulfate |
| US11344570B2 (en) | 2017-12-20 | 2022-05-31 | Oji Holdings Corporation | Pentosan polysulfate and medicine containing pentosan polysulfate |
| CN117624404A (en) * | 2024-01-25 | 2024-03-01 | 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 |
| 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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