CN108929435B - Method for synthesizing polysorbate 80 with low-polysorbitol content - Google Patents
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Abstract
The method for synthesizing polysorbate 80 with low content of polysorbitol comprises the following steps: preparing dehydrated sorbitol: dehydrating sorbitol under the action of a catalyst in a vacuum state to prepare dehydrated sorbitol; separating the polysorbate from the sorbitan: mixing the sorbitan, the low carbon alcohol and the adsorbent, heating to dissolve, cooling to crystallize, and vacuum drying to obtain refined sorbitan; preparing sorbitan oleate: mixing refined sorbitan with oleic acid, and then carrying out esterification reaction under the action of a catalyst to prepare sorbitan oleate; synthesis of polysorbate 80: sorbitan oleate and about 20 mol of ethylene oxide are subjected to addition polymerization reaction under the action of a catalyst to prepare polysorbate 80. The invention removes the polysorbitol, controls the hydroxyl value of the refined sorbitan and ensures the relative stability of the components; and the content of the polysorbate 80 is reduced (less than 0.1%), and the biological safety of the polysorbate 80 product is improved.
Description
Technical Field
The invention relates to a method for synthesizing polysorbate 80 with low sorbitol oligomer content, and belongs to the technical field of chemical synthesis.
Technical Field
Polysorbate 80 (also called tween-80, polyoxyethylene (20) sorbitan monooleate) is widely used as a dispersant, a thickener, an antifogging agent, a penetrant and the like in the fields of medicine, biological products, food, cosmetics and chemical industry, and in recent years, the product is used in a large amount in biological products, particularly in the production of vaccines.
The synthesis routes of polysorbate 80 reported in the literature are summarized as follows:
route one: firstly, taking sorbitol as a raw material, directly carrying out esterification reaction with oleic acid under the action of acid, and simultaneously carrying out intramolecular dehydration reaction to prepare span 80; or sorbitan is prepared by dehydration reaction of sorbitol under base catalysis, and then span 80 is prepared by esterification reaction of sorbitan and oleic acid (see US 4297290). And then span 80 and ethylene oxide are subjected to addition polymerization reaction at a molar ratio of about 1:20 to prepare the polysorbate 80.
And a second route: firstly, performing dehydration reaction on sorbitol under the action of a catalyst to prepare sorbitan, and then separating and refining each component in the sorbitan to respectively prepare high-purity primary sorbitan and secondary sorbitan; then mixing high-purity sorbitol, mono-sorbitan and di-sorbitan according to a certain proportion and then carrying out addition polymerization reaction with ethylene oxide, or mixing the high-purity sorbitol, mono-sorbitan and di-sorbitan with ethylene oxide respectively according to a certain proportion after carrying out addition polymerization reaction to prepare polyoxyethylene sorbitan; the obtained polyoxyethylene sorbitan is subjected to esterification reaction with oleic acid under the action of a catalyst to prepare polysorbate 80 (see Chinese patents CN102352032B, CN102127217B, CN101983977B and CN 101701065B).
In the first route, sorbitol inevitably generates polysorbate which is usually over 5% during dehydration and esterification, and if the sorbitol is directly used for synthesizing polysorbate 80 without separation, ethylene oxide polymer and oleate of the polysorbate with larger molecules can be generated, and the safety of the polysorbate 80 is seriously affected by the existence of the macromolecular substances; in addition, in the method, due to the limitation of the hydroxyl value of span 80, after the esterification reaction of sorbitol and oleic acid is completed, the dehydration reaction of sorbitol hydroxyl is further carried out to control the hydroxyl value of span 80 within a certain range, so that the reaction time is prolonged.
The second route can solve the problem of residue of the polysorbate 80 by controlling the composition of the sorbitan with different degrees, but the sorbitol with different dehydration degrees needs to be respectively refined and purified, so that the process is complex, the steps are multiple, the large-scale production efficiency is low, and the cost is high.
Disclosure of Invention
In view of the above problems of the prior art, the present invention aims to provide a method for synthesizing polysorbate 80 with an oligo-sorbitol content.
The technical scheme adopted by the invention is as follows:
a method for synthesizing polysorbate 80 with low sorbitol content is characterized by comprising the following steps:
preparing dehydrated sorbitol: under the vacuum state, sorbitol generates intramolecular dehydration reaction under the action of a catalyst to prepare sorbitan;
separating the polysorbate from the sorbitan: mixing the sorbitan, the low-carbon alcohol and the adsorbent according to a certain proportion, heating to dissolve, cooling to crystallize, vacuum drying and the like to obtain refined sorbitan;
preparing sorbitan oleate: mixing the refined sorbitan obtained in the step II with oleic acid according to a certain proportion, and then carrying out esterification reaction under the action of a catalyst to prepare sorbitan oleate (namely span 80);
fourth, synthesis of polysorbate 80: and (5) performing addition polymerization reaction on the sorbitan oleate obtained in the step (a) and ethylene oxide under the action of a catalyst to prepare the polysorbate 80.
Wherein: preparing the dehydrated sorbitol:
the catalyst is a protonic acid such as sulfuric acid, phosphoric acid, phosphorous acid, hypophosphorous acid or a solid acid, of which phosphorous acid and hypophosphorous acid are preferred, and hypophosphorous acid is more preferred; the using amount of the catalyst is 0.1-0.6% of the mass of the sorbitol, and preferably 0.4-0.5%;
the dehydration reaction is carried out under the vacuum degree of less than or equal to-0.09 MPa (G), preferably less than or equal to-0.095 MPa (G), and more preferably less than or equal to-0.098 MPa (G); the temperature of the dehydration reaction is 100-160 ℃, and preferably 120-140 ℃; the dehydration reaction time is 1-8 h, preferably 4-5 h;
according to the preparation method, the water loss of the sorbitol is about 1 mol, the obtained sorbitan mainly comprises sorbitol, mono-sorbitan, di-sorbitan and polysorbitol, the hydroxyl value is about 1100-1400 mgKOH/g, and the content of the polysorbitol is less than or equal to 10%;
the separation of the sorbitan-modified sorbitan:
the low carbon alcohol is one or a mixture of methanol and ethanol, and the addition amount of the low carbon alcohol is 0.5-10 times, preferably 1-5 times, and more preferably 2-3 times of the mass of the sorbitan;
the adsorbent is one or a mixture of more of active carbon, silica gel and magnesium silicate, and the addition amount of the adsorbent is 0.01 times of the mass of the sorbitan.
The temperature for heating and dissolving is 60-80 ℃;
the crystallization temperature is-30 to 0 ℃, preferably-25 to 0 ℃, and more preferably-10 to-5 ℃ during the temperature reduction crystallization; the crystallization time is 1-10 hours, preferably 3-8 hours, and more preferably 4-5 hours;
the vacuum drying is carried out, wherein the vacuum degree is less than or equal to-0.080 MPa (G), preferably less than or equal to-0.095 MPa, and more preferably less than or equal to-0.098 MPa; the drying temperature is 30-80 ℃, and preferably 40-50 ℃; the drying time is 6-8 hours;
according to the refining method, the obtained refined sorbitan has a hydroxyl value of 1250-1350 mgKOH/g, the proportion of main components of sorbitol, sorbitan monolaurate and sorbitan monolaurate is 0-10: 40-80: 0-20, and the content of polysorbate is less than or equal to 0.1%, so that the refined sorbitan can be directly used for preparing sorbitan oleate;
step three, preparing the sorbitan oleate:
the catalyst is oxide, hydroxide or carbonate and bicarbonate of alkali metal and alkaline earth metal, such as calcium oxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate and calcium carbonate, wherein the preferred is potassium carbonate, sodium carbonate, potassium hydroxide and sodium hydroxide, and the more preferred is potassium carbonate, and the addition amount of the potassium carbonate is 0.2-1%, preferably 0.4-0.5% of the mass of the refined sorbitan;
the ratio of the sorbitan to the oleic acid is 1: 2.28-3.10, preferably 1: 2.6-3.0, more preferably 1: 2.8-2.9.
The esterification reaction temperature is 180-230 ℃, preferably 200-220 ℃, and the esterification reaction time is 5-6 hours.
The catalyst is sodium hydroxide, potassium hydroxide or sodium methoxide and potassium methoxide, and the addition amount of the catalyst is 0.006-0.0125 times of the mass of sorbitan oleate;
the invention provides a method for synthesizing polysorbates 80, which removes polysorbates in sorbitol through pre-dehydration and refining of sorbitol, controls the hydroxyl value of refined sorbitan and ensures the relative stability of the refined sorbitan components; and because of the pre-dehydration and refining of the sorbitol, compared with the esterification which takes the sorbitol as the raw material, the method shortens the reaction time, reduces the probability of polymer formation of sorbitol in the esterification reaction process, reduces the content of the polysorbitol in the polysorbate 80 (less than 0.1 percent), improves the biological safety of the polysorbate 80 product, and realizes the large-scale production of the polysorbate 80.
Detailed Description
In order to better illustrate the invention, we will cite the following examples, but the invention is not limited to the following examples.
Example 1 preparation of sorbitan:
example 1.1 in a 2L reaction kettle put into 1200g sorbitol, 5g sulfuric acid, vacuum dehydration reaction, vacuum degree less than or equal to-0.095 Mpa (G), dehydration temperature 120~140 degrees C, time 5 hours. The resulting sorbitan had a hydroxyl value of 1150 mgKOH/g.
Example 1.2 is essentially the same as example 1.1, with the following changes: phosphoric acid is used for replacing sulfuric acid, and the obtained sorbitan hydroxyl value is 1210 mgKOH/g;
example 1.3 is essentially the same as example 1.1, with the following changes: solid acid is used for replacing sulfuric acid, and the obtained sorbitan has a hydroxyl value of 1260 mgKOH/g;
example 1.4 is essentially the same as example 1.1, with the following changes: phosphorous acid is used for replacing sulfuric acid, and the obtained sorbitan hydroxyl value is 1300 mgKOH/g;
example 1.5 is essentially the same as example 1.1 with the following modifications: hypophosphorous acid was used instead of sulfuric acid, and the resulting sorbitan had a hydroxyl value of 1320 mgKOH/g.
Example 2 purification of sorbitan:
example 2.1 the preparation method comprises the steps of taking 500g of the sorbitan, adding 1250g of methanol and 5g of activated carbon, heating to 60-80 ℃, stirring until the sorbitan is completely dissolved, slowly cooling to-10 ℃, then preserving heat, crystallizing for 4 hours, and filtering. And drying the filter cake for 6 hours at 40-50 ℃ under reduced pressure, wherein the vacuum degree is less than or equal to-0.098 MPa. The obtained refined sorbitan has a hydroxyl value of 1300mgKOH/g, wherein the ratio of sorbitol to mono-and di-sorbitan is 10:75:15, and the content of polysorbitol is 0.04%.
Example 2.2 is essentially the same as example 2.1, with the following changes: slowly cooling to-30 deg.C, and crystallizing for 4 hr to obtain refined sorbitan with hydroxyl value of 1340mgKOH/g, wherein the ratio of sorbitol to mono-and di-sorbitan is 8:75:17, and the content of polysorbate is 0.10%.
Example 2.3 is essentially the same as example 2.1, with the following changes: slowly cooling to 0 deg.C, keeping the temperature, crystallizing for 4 hr to obtain refined sorbitan with hydroxyl value of 1250mgKOH/g, wherein the ratio of sorbitol to mono-and di-sorbitan is 0:80:20, and the content of polysorbate is 0.06%.
Example 2.4 substantially the same as example 2.1, ethanol was used instead of methanol, and the resulting refined sorbitan had a hydroxyl number of 1300mgKOH/g, wherein the ratio of sorbitol, mono-and di-sorbitan was 6:78:16, and the polysorbitol content was 0.09%.
Example 2.5 is essentially the same as example 2.1, with the following changes: the silica gel is used for replacing active carbon, and the obtained refined sorbitan has a hydroxyl value of 1300mgKOH/g, wherein the ratio of sorbitol to mono-sorbitan to di-sorbitan is 5:80:15, and the content of polysorbitol is 0.08%.
Example 2.6 is essentially the same as example 2.1, with the following changes: the magnesium silicate is used for replacing active carbon, and the obtained refined sorbitan has a hydroxyl value of 1300mgKOH/g, wherein the ratio of sorbitol to mono-sorbitan to di-sorbitan is 5:80:15, and the content of polysorbitol is 0.08%.
Example 3 preparation of sorbitan oleate:
example 3.1 in a 2L reaction vessel, 400g of the refined sorbitan prepared in example 2 (0.06% of polysorbate), 1145g of oleic acid, and 2g of sodium hydroxide as a catalyst were charged, and the esterification reaction was carried out at a temperature of 200 to 220 ℃ for 5 hours to obtain sorbitan oleate, wherein the polysorbate content was 0.08%.
Example 3.2 is essentially the same as example 3.1, with the following changes: potassium hydroxide is used for replacing sodium hydroxide, the reaction time is 5 hours, and the content of the polysorbitol in the obtained sorbitan oleate is 0.09%.
Example 3.3 is essentially the same as example 3.1, with the following changes: sodium carbonate is used for replacing sodium hydroxide, the reaction time is 7 hours, and the content of the polysorbitol in the obtained sorbitan oleate is 0.08%.
Example 3.4 is essentially the same as example 3.1, with the following changes: potassium carbonate is used for replacing sodium hydroxide, the reaction time is 6 hours, and the content of the polysorbitol in the obtained sorbitan oleate is 0.06 percent.
Example 4 preparation of polysorbate 80:
example 4.1A 2L autoclave was charged with 400g of sorbitan oleate prepared in example 3, 5g of sodium hydroxide, and then evacuated to a degree of vacuum of-0.1 MPa in the autoclave under a nitrogen atmosphere at 0.3MPa, and the nitrogen atmosphere and the vacuum operation were repeated three times. Heating to 90-120 ℃, and degassing for 1 hour in vacuum. And slowly introducing 800g of ethylene oxide, controlling the pressure of the reaction kettle to be less than or equal to 0.3MPa and the reaction temperature to be 100-160 ℃ until the introduction of the ethylene oxide is finished. After the feeding is finished, the temperature is preserved and the reaction kettle is aged until the pressure difference between the inside and the outside of the reaction kettle is reduced to 0, and the temperature is reduced and the discharging is carried out. The polysorbate 80 obtained contained 0.03% of polysorbate.
Example 4.2 is essentially the same as example 4.1, with the following changes: potassium hydroxide is adopted to replace sodium hydroxide, and the content of the polysorbate 80 is 0.03 percent
Example 4.3 is essentially the same as example 4.1, with the following changes: sodium methoxide is adopted to replace sodium hydroxide, and the content of the polysorbitol in the obtained polysorbate 80 is 0.03%.
Example 4.4 is essentially the same as example 4.1, with the following changes: potassium methoxide is adopted to replace sodium hydroxide, and the content of the polysorbitol in the obtained polysorbate 80 is 0.02 percent.
Example 5, including all the steps of examples 1-4, and substantially the same as examples 1-4, but wherein the catalyst of step was sulfuric acid; the adding amount is 0.4 percent of the mass of the sorbitol;
the dehydration reaction is carried out under the vacuum degree of less than or equal to-0.098 MPa (G); the temperature of the dehydration reaction is 100-120 ℃; the dehydration reaction time is 4 hours;
according to the preparation method, the water loss of the sorbitol is about 1 mol, the obtained sorbitan mainly comprises sorbitol, mono-sorbitan, di-sorbitan and polysorbitol, the hydroxyl value is about 1100-1400 mgKOH/g, and the content of the polysorbitol is less than or equal to 10%;
the separation of the sorbitan-modified sorbitan:
the low-carbon alcohol is isopropanol, and the addition amount of the low-carbon alcohol is 0.5 time of the mass of the sorbitan;
the temperature for heating and dissolving is 50 ℃;
the temperature is reduced for crystallization, and the crystallization temperature is-25-0 ℃; the crystallization time was 5 hours;
the vacuum drying is carried out, wherein the vacuum degree is less than or equal to-0.098 MPa; the drying temperature is 40-50 ℃; the drying time was 6 hours;
according to the refining method, the obtained refined sorbitan has a hydroxyl value of about 1250-1350 mgKOH/g, and the main components of sorbitol, sorbitan and di-sorbitan have a ratio of about 0: 40: 20, the content of the polysorbitol is less than or equal to 0.1 percent, and the polysorbitol can be directly used for synthesizing sorbitan oleate;
step three, preparing the sorbitan oleate: the catalyst is calcium oxide, and the addition amount of the catalyst is 0.4 percent of the mass of the refined sorbitan;
the esterification reaction temperature is 180-200 ℃.
Example 6, substantially the same as example 5, except that the step of preparing sorbitan is performed, the catalyst is a solid acid; the adding amount is 0.5 percent of the mass of the sorbitol;
the dehydration reaction is carried out under the vacuum degree of less than or equal to-0.09 MPa (G); the temperature of the dehydration reaction is 140-160 ℃; the dehydration reaction time is 8 h;
the separation of the sorbitan-modified sorbitan: the low-carbon alcohol is a mixture of methanol, ethanol and isopropanol in equal proportion, and the addition amount of the low-carbon alcohol is 10 times of the mass of the sorbitan;
the temperature for heating and dissolving is 90 ℃;
the temperature is reduced for crystallization, and the crystallization temperature is 10 ℃; the crystallization time was 1 hour;
the vacuum drying is carried out, and the vacuum degree is less than or equal to-0.095 MPa; the drying temperature was 30 ℃; the drying time was 8 hours;
according to the refining method, the obtained refined sorbitan has a hydroxyl value of about 1250-1350 mgKOH/g, and the main components of the refined sorbitan are sorbitol, sorbitan and di-sorbitan in a ratio of about 10: 80:0 percent, and the content of the polysorbitol is less than or equal to 0.1 percent, can be directly used for synthesizing the sorbitan oleate;
step three, preparing the sorbitan oleate: the catalyst is calcium hydroxide, and the addition amount of the catalyst is 0.2 percent of the mass of the refined sorbitan;
the esterification temperature was 230 ℃.
Example 7, which is substantially the same as example 5, except that in the step of preparing sorbitan, the amount of the catalyst added is 0.1% by mass of sorbitol;
the dehydration reaction temperature is 100 ℃; the dehydration reaction time is 1 h;
the separation of the sorbitan-modified sorbitan: the addition amount of the low carbon alcohol is 2 times of the mass of the sorbitan;
the temperature for heating and dissolving is 50 ℃;
the temperature is reduced for crystallization, and the crystallization time is 10 hours;
vacuum drying is carried out, wherein the vacuum degree is less than or equal to-0.080 MPa (G); the drying temperature is 80 ℃; the drying time was 6 hours;
step three, preparing the sorbitan oleate: the esterification reaction temperature is 200-220 ℃, and the esterification reaction time is 5-6 hours.
Example 8, which is substantially the same as example 5, except that in the preparation of sorbitan described in the step, the amount of the catalyst added is 0.1% by mass of sorbitol;
the dehydration reaction temperature is 100 ℃; the dehydration reaction time is 1 h;
the separation of the sorbitan-modified sorbitan: the addition amount of the low carbon alcohol is 5 times of the mass of the sorbitan;
the temperature is reduced for crystallization, and the crystallization time is 3 hours;
vacuum drying is carried out, wherein the vacuum degree is less than or equal to-0.080 MPa (G); the drying temperature is 30-80 ℃, and preferably 40-50 ℃; the drying time is 6-8 hours;
step three, preparing the sorbitan oleate: the catalyst is calcium carbonate, and the adding amount of the catalyst is 1% of the mass of the refined sorbitan.
Claims (4)
1. A method for synthesizing polysorbate 80 with low sorbitol content is characterized by comprising the following steps:
preparing dehydrated sorbitol: under the vacuum state, sorbitol generates dehydration reaction under the action of a catalyst to prepare the sorbitan;
separating the polysorbate from the sorbitan: mixing the sorbitan, the low-carbon alcohol and the adsorbent according to a certain proportion, heating for dissolving, cooling for crystallizing, and vacuum drying to obtain refined sorbitan;
preparing sorbitan oleate: mixing the refined sorbitan and oleic acid obtained in the step II according to a certain proportion, and then carrying out esterification reaction under the action of a catalyst to prepare sorbitan oleate;
synthesis of polysorbate 80: performing addition polymerization reaction on the sorbitan oleate obtained in the step three and 20 moles of ethylene oxide under the action of a catalyst to prepare polysorbate 80;
the preparation method comprises the steps of preparing the sorbitan, wherein the catalyst is protonic acid; the using amount of the protonic acid is 0.1-0.6% of the mass of the sorbitol;
the dehydration reaction is carried out under the vacuum degree of less than or equal to-0.09 MPa;
the temperature of the dehydration reaction is 100-160 ℃; the dehydration reaction time is 1-8 h;
according to the preparation method, the water loss of sorbitol is 1 mol, the obtained sorbitan mainly comprises sorbitol, mono-sorbitan, di-sorbitan and polysorbitol, the hydroxyl value is 1100-1400 mgKOH/g, and the content of polysorbitol is less than or equal to 10%;
separating the polysorbate from the sorbitan, wherein the low-carbon alcohol is one or a mixture of methanol, ethanol and isopropanol, and the addition amount of the low-carbon alcohol is 0.5-10 times of the mass of the sorbitan;
the adsorbent is active carbon, silica gel or magnesium polysilicate, and the using amount of the adsorbent is 0.01 to 0.1 time of the mass of the sorbitan;
the temperature for heating and dissolving is 50-90 ℃;
the temperature is reduced for crystallization, and the crystallization temperature is-30-10 ℃; the crystallization time is 1-10 hours;
the vacuum drying is carried out, and the vacuum degree is less than or equal to-0.080 MPa; the drying temperature is 30-80 ℃; the drying time is 6-8 hours;
according to the refining method, the obtained refined sorbitan has a hydroxyl value of 1250-1350 mgKOH/g, the mass ratio of main components of sorbitol to mono-and di-sorbitan is 0-10: 40-80: 0-20, and the content of polysorbitol is less than or equal to 0.1%, so that the refined sorbitan can be directly used for synthesizing sorbitan oleate;
step three, preparing the sorbitan oleate: the catalyst is oxides, hydroxides or carbonates and bicarbonates of alkali metals and alkaline earth metals, and the using amount of the catalyst is 0.2-1% of the mass of the refined sorbitan;
the mass ratio of the refined sorbitan to the oleic acid is 1: 2.28-3.10;
the esterification reaction temperature is 180-230 ℃, and the esterification reaction time is 5-6 hours.
2. The method for synthesizing polysorbate 80 having an oligo-sorbitol content according to claim 1,
the preparation method comprises the steps of preparing the sorbitan, wherein the catalyst is selected from sulfuric acid, phosphoric acid, phosphorous acid, hypophosphorous acid or solid acid; the using amount is 0.4-0.5% of the mass of the sorbitol;
the dehydration reaction is carried out under the vacuum degree of less than or equal to-0.095 MPa; the temperature of the dehydration reaction is 120-140 ℃; the dehydration reaction time is 4-5 h;
separating the polysorbate from the sorbitan, wherein the addition amount of the low carbon alcohol is 1-5 times of the mass of the sorbitan;
the temperature for heating and dissolving is 60-80 ℃;
the temperature is reduced for crystallization, and the crystallization temperature is-30-0 ℃; the crystallization time is 3-8 hours;
the vacuum drying is carried out, and the vacuum degree is less than or equal to-0.095 MPa; the drying temperature is 40-50 ℃;
step three, preparing the sorbitan oleate, wherein the catalyst is carbonate of alkali metal, and the using amount of the carbonate is 0.4-0.5% of the mass of the refined sorbitan oleate;
the esterification reaction temperature is 200-220 ℃.
3. The method for synthesizing polysorbate 80 having an oligo-sorbitol content according to claim 2,
the preparation method comprises the steps of preparing the sorbitan, wherein the catalyst is hypophosphorous acid;
the dehydration reaction is carried out under the vacuum degree of less than or equal to-0.098 MPa;
separating the polysorbate from the sorbitan, wherein the addition amount of the low-carbon alcohol is 2-3 times of the mass of the sorbitan;
the temperature is reduced and the crystallization temperature is-10 to-5 ℃; the crystallization time is 4-5 hours;
the vacuum drying is carried out, wherein the vacuum degree is less than or equal to-0.098 MPa;
step three, preparing the sorbitan oleate, wherein the catalyst is potassium carbonate.
4. The method for synthesizing polysorbate 80 having an oligosorbitan content according to any one of claims 1 to 3, wherein the polysorbate 80 prepared according to the above method has a polysorbitan content of < 0.1%.
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| CN101925632A (en) * | 2008-01-28 | 2010-12-22 | 日油株式会社 | Process for production of polyoxyethylene sorbitan fatty acid esters |
| CN101948451A (en) * | 2010-08-18 | 2011-01-19 | 南京威尔化工有限公司 | Preparation method of high-purity 1,4-sorbitan |
| CN102352031A (en) * | 2011-07-21 | 2012-02-15 | 南京威尔化工有限公司 | Method for preparing high purity polysorbate 80 through synthesizing three effective components and mixing |
| CN106749118A (en) * | 2016-11-23 | 2017-05-31 | 张家港格瑞特化学有限公司 | The smooth caprylate emulsifying agent of sorb |
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