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Method for synthesizing high-purity polysorbate-80

A technology of polysorbate and synthesis method, applied in chemical instruments and methods, transportation and packaging, dissolution, etc., can solve the problem of poor color of polysorbate-80 (I), low purity of polysorbate-80, and product quality Difficult to control and other problems, to achieve the effect of perfect emulsification and solubilization performance, good clinical safety, and less harmful impurities

Active Publication Date: 2010-05-05
NANJING WELL BIOCHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0011] Fourth, the ester content formed by other fatty acids in the oleic acid used and sorbitan is high, which is 20%-30%, which has limitations in pharmaceutical application;
[0012] Fifth, the obtained polysorbate-80 (I) has poor color and does not meet the requirements of pharmaceutical applications (such as being used for injections);
[0013] Sixth, the plasticity of the production operation is poor, and the product quality is not easy to control
[0014] Some different traditional Chinese medicine injections had the same serious side effects in clinical use, most of which were caused by the low purity of polysorbate-80 in the excipients

Method used

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Examples

Experimental program
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Embodiment 1

[0044] The synthesis of embodiment 1 sorbitan

[0045] Example 1.1 Put 3500g of 70% sorbitol into the kettle, dehydrate at 100-120°C for 3h, when the temperature is lowered to 80°C, add 120ml of 20% sulfuric acid aqueous solution, and stir the reaction for 5 hours at 750mmHg vacuum and 105-110°C; The aqueous solution of sodium hydroxide was neutralized to neutral, decolorized with activated carbon, filtered, evaporated to dryness under reduced pressure, and dried in vacuo to obtain white solid sorbitan with a hydroxyl value of 1100 mgKOH / g.

[0046] Example 1.2 is basically the same as Example 1.1, but with the following changes, 120ml of 20% aqueous sulfuric acid is replaced with 24.5g of phosphorous acid, and the hydroxyl value of the obtained sorbitan is 1092mgKOH / g.

[0047] Example 1.3 is basically the same as Example 1.1, but with the following changes, 120ml of 20% aqueous sulfuric acid is replaced with 24.5g of p-toluenesulfonic acid, and the hydroxyl value of the obta...

Embodiment 2

[0051] The synthesis of embodiment 2 sorbitan polyoxyethylene ethers

[0052] Example 2.1 Add 102g of sorbitan and 1.0g of NaOH (or KOH) solid in a pressure-resistant reactor, replace it with nitrogen and raise the temperature to 90°C, slowly add 618g of ethylene oxide, and react at 110°C and 0.4MPa , until the pressure no longer decreases, the temperature is lowered and the material is discharged, neutralized with 10g 600NS, vacuum dehydrated, filtered to obtain polyoxyethylene sorbitan ether, the measured hydroxyl value is 151.5mgKOH / g, and the chromaticity APHA<30.

[0053] Embodiment 2.2 is substantially the same as embodiment 2.1, but has following changes, replaces 1.0g NaOH (or KOH) solid with the mineral oil solution of 3.3g30% KH (or NaH), obtains sorbitan polyoxyethylene ether, measures The hydroxyl value is 149.2mgKOH / g, and the chroma APHA<20.

[0054] Embodiment 2.3 is substantially the same as embodiment 2.1, but following changes are arranged: the addition of a...

Embodiment 3

[0058] The synthesis of embodiment 3 polysorbate-80

[0059] The main physicochemical data of the polysorbate-80 obtained by the following different methods are listed in Table 1.

[0060] Embodiment 3.1 adds the sorbitan polyoxyethylene ether that 412g embodiment 2 makes in reactor, 132g oleic acid (90.5%) and 5gNaH 2 PO 3 , stirred and reacted at 220° C. for 5 h under nitrogen blowing, cooled to room temperature, treated with bleaching earth and diatomaceous earth, and filtered to obtain high-purity polysorbate-80.

[0061] Example 3.2 is basically the same as Example 3.1, but with the following changes, replacing 5g NaH with 5g phosphorous acid 2 PO 3 .

[0062] Example 3.3 is basically the same as Example 3.1, but with the following changes, replacing 5g NaH with 5g p-toluenesulfonic acid monohydrate 2 PO 3 .

[0063] Embodiment 3.4 is substantially the same as embodiment 3.1, but with the following changes, the purity of oleic acid used is 95.6%.

[0064] Embodime...

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Abstract

The invention relates to a method for synthesizing high-purity polysorbate-80. The polysorbate-80 (I) is a partial esterified product of a sorbitan ethyoxyl compound and oleic acid. The method comprises the following steps of: (1) partially dehydrating sorbitol as a raw material under the action of an acid catalyst in a state of vacuum to obtain sorbitan (II); (2) carrying out addition polymerization on the sorbitan (II) and oxirane under the action of a base catalyst to obtain sorbitan polyethenoxy ether (III), wherein the addition number of the oxirane is 20; (3) reacting the sorbitan polyethenoxy ether (III) with the high-purity oleic acid under the action of an esterifying catalyst and refining to obtain the high-purity polysorbate-80. The invention leads the emulsifying and solubilizing performance of products to be more perfect and the quality of the products to easily meet the requirement of an injection class and has easily controlled quality and good stability; and the high-purity polysorbate-80 has lower blood dissolving rate in same concentration, and predictable and safer clinical use by being used as an auxiliary material for injection.

Description

technical field [0001] The invention relates to a chemical synthesis method, in particular to a synthesis method of high-purity polysorbate-80 (I). Background technique [0002] Polysorbate-80 (I), also known as polyoxyethylene (20) sorbitan monooleate, it is a kind of hydrophilic nonionic surfactant, because it has better solubilizing effect, in When preparing injections of poorly soluble drugs, it is often used as a cosolvent, emulsifier and stabilizer. [0003] The synthetic method of (I) reported in the literature usually has the following two kinds: [0004] Method 1: Sorbitol and oleic acid undergo simultaneous dehydration and esterification reactions under the action of a basic catalyst to obtain sorbitan monooleate, which is then condensed with 20 mole fractions of ethylene oxide to obtain polysorbate- 80(I). [0005] Method 2: Sorbitol is first dehydrated under the action of an acidic or alkaline catalyst to obtain sorbitan, then esterified with oleic acid to obt...

Claims

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Application Information

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IPC IPC(8): C08G65/28B01F17/42C09K23/42
Inventor 陈新国贾建国吴仰波吴仁荣高正松沈德渊李晓光费红
Owner NANJING WELL BIOCHEM
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