Synthesis method of middle-molecular-weight hydroxyethyl starch

A technology of hydroxyethyl starch and synthesis method, which is applied in the field of medicine and chemical industry, can solve the problems of reduced reactivity, prolonged catabolism of hydroxyethyl starch, etc., and achieves the effect of easy separation

Active Publication Date: 2012-01-18
WUHAN HUST LIFE SCI & TECH
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  • Abstract
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Problems solved by technology

[0011] The hydroxyethyl reaction can usually be produced at the C2, C6, and C3 positions of the glucose unit in starch, and the reactivity decreases sequentially. The pharmacological properties of product

Method used

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  • Synthesis method of middle-molecular-weight hydroxyethyl starch

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Embodiment 1

[0024] Preparation of hydroxyethyl starch 130 / 0.4

[0025] Take the waxy cornstarch hydrolyzate 1800g that weight average molecular weight is 110,000-150,000 and 80% product is distributed in 15000 to 500000, add purified water and be made into 25% solution and be placed in 15L reactor, in purifying high-purity N 2 Under protection, the temperature of the jacketed water bath was controlled at about 30°C, and vigorously stirred, 804ml of 10N NaOH solution and 415g of chloroethanol were added respectively, and the stirring was continued for 8 hours, and then the reaction solution was neutralized with 10N hydrochloric acid until the pH value was close to 7. The reaction liquid is treated with a 15,000 molecular weight ultrafiltration cut-off membrane to remove sodium chloride and some low-molecular organic residual components contained in the reaction liquid. Decolorize the cut-off part of the above-mentioned membrane separation through activated carbon, filter, and spray-dry the...

Embodiment 2

[0027] Preparation of hydroxyethyl starch 200 / 0.5,

[0028] Take 20Kg of waxy corn starch hydrolyzate starch hydrolyzate with a weight average molecular weight of 180,000-290,000 and 80% product distribution in the range of 15,000 to 800,000, add purified water to form a 25% solution and place it in a 200L reactor, and pass through the purified high-purity N 2 For protection, the temperature of the jacketed water bath is controlled at about 30°C, and 10.5L of 10N sodium hydroxide solution and 5.2Kg of chloroethanol are respectively added under stirring, and the stirring is continued for 12 hours. The reaction solution was neutralized with 10N hydrochloric acid until the pH was close to 7. After the reaction solution is treated with a 30,000 molecular weight hollow fiber cut-off membrane, decolorize the membrane separation cut-off part with activated carbon, filter, and spray dry to obtain white powder hydroxyethyl starch 200 / 0.5. The product MS, C2:C6 was determined by GC met...

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Abstract

The invention provides a synthesis method of middle-molecular-weight hydroxyethyl starch. The synthesis method comprises the following steps: carrying out hydroxyethyl substitution reaction on waxy corn starch hydrolyzate and a hydroxyethyl substituting agent under the conditions that water is used as a solvent and sodium hydroxide is taken as a catalyst; and carrying out ultrafiltration interception membrane separation and activated carbon decoloration, filtering, and carrying out spray drying on filtrate so as to obtain the white powdery middle-molecular-weight hydroxyethyl starch product. According to the invention, an adopted aqueous phase synthesis method has the advantages that an ideal molar degree of substitution (MS) of hydroxyethyl and an ideal substitution position ratio (C2:C6) are conveniently controlled in the reaction, and the byproducts of the reaction are easy to separate; and under the condition of the aqueous phase synthesis method, the reaction is a room temperature reaction, reactants and the catalyst are completely dissolved in the reaction system, the substitution positions are uniformly distributed in the product, the reaction byproducts such as sodium chloride, chlorohydrin, cyclochloroethane, glycol and the like can be easily removed once through a membrane separation technology, the obtained product has proper MS and a ratio of C2:C6, and the obtained product quality can reach or be superior to the existing national drug standard.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, and relates to a production method of medium molecular weight hydroxyethyl starch, in particular to a synthesis method of hydroxyethyl starch 200 / 0.5 and hydroxyethyl starch 130 / 04. Background technique [0002] The main physiological functions of plasma volume expanders are to maintain normal plasma colloid osmotic pressure and expand plasma volume, improve hemodynamics, microcirculatory blood flow, hemorheology, oxygen supply and organ function. It is used for the treatment of shock caused by massive bleeding, burns or other trauma. An ideal plasma volume expander, which can quickly replenish lost blood volume, restore hemodynamic balance, restore normal microcirculatory blood flow, improve blood rheology, improve oxygen supply and organ function, and have a long enough residence time in blood vessels And good tolerance, and easy to be metabolized and excreted in the body. [000...

Claims

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Application Information

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IPC IPC(8): C08B35/04
Inventor 杨祥良阮健周小顺万江陵李进贺容丽王芳朱吉胜鲁珍娥岳蓉黄邦红
Owner WUHAN HUST LIFE SCI & TECH
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