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Preparation process for reducing disubstitution proportion of hydroxyethyl starch with middle molecular weight

A technology of hydroxyethyl starch and preparation process, which is applied in the field of medicine and chemical industry, and can solve problems such as imbalance, influence on metabolism, and chemical structure change of glucose residues, and achieve the effect of improving drug safety and reducing production

Active Publication Date: 2012-11-07
SHANDONG QIDU PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Double or multiple substitutions at the above positions will cause changes and imbalances in the chemical structure of glucose residues, which will affect the decomposition and recognition of hydroxyethyl starch by amylase in the human body, thereby affecting metabolism

Method used

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  • Preparation process for reducing disubstitution proportion of hydroxyethyl starch with middle molecular weight
  • Preparation process for reducing disubstitution proportion of hydroxyethyl starch with middle molecular weight

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Take 300 kg of amylopectin with a weight average molecular weight of 89 500, put it into 1 300 L of purified water, stir well, and slowly add 15 kg of dissolved sodium hydroxide (the molar ratio to amylopectin is 0.20) at a flow rate of 7.0 L / min Pumped into the pipeline reactor. At the same time, 50kg of ethylene oxide (with a molar ratio of 0.60 to amylopectin) was pumped into the pipeline reactor at a flow rate of 0.3L / min. The tube reactor was kept at 25°C. Feed liquid was reacted for 5 hours with the flow velocity of 7.0L / min in the pipeline reactor.

[0024] Pump the reaction feed liquid into the storage tank, add 36% hydrochloric acid (W / V), neutralize the sodium hydroxide in it to near neutrality, add 3‰ activated carbon for needles, stir and raise the temperature to 90°C, and keep it warm for 1 hour, Filtrate through a decarburization filter while hot.

[0025] The filtrate was cooled to 35°C and ultrafiltered through a plate-type ultrafiltration membrane w...

Embodiment 2

[0028] Take 450 kg of amylopectin with a weight average molecular weight of 10 200, put it into 1 300 L of purified water, stir well, and slowly add 50 kg of dissolved sodium hydroxide (the molar ratio to amylopectin is 0.40) at a flow rate of 8.2 L / min Pumped into the pipeline reactor. At the same time, 90 kg of ethylene oxide (with a molar ratio of 0.73 to amylopectin) was pumped into the pipeline reactor at a flow rate of 0.35 L / min. The tube reactor was kept at 35°C. Feed liquid was reacted for 7 hours at a flow rate of 8.0 L / min in the pipeline reactor.

[0029] Pump the reaction feed liquid into the storage tank, add 36% hydrochloric acid (W / V), neutralize the sodium hydroxide in it to near neutrality, add 3‰ activated carbon for needles, stir and raise the temperature to 90°C, and keep it warm for 1 hour, Filtrate through a decarburization filter while hot.

[0030] The filtrate was cooled to 30°C and ultrafiltered through a plate ultrafiltration membrane with a mole...

Embodiment 3

[0033] Take 500 kg of amylopectin with a weight average molecular weight of 87 500, put it into 1 300 L of purified water, stir well, and slowly add 37 kg of dissolved sodium hydroxide (the molar ratio to amylopectin is 0.33) at a flow rate of 9.0 L / min Pumped into the pipeline reactor. At the same time, 110 kg of ethylene oxide (with a molar ratio of 0.80 to amylopectin) was pumped into the pipeline reactor at a flow rate of 0.40 L / min. The tube reactor was kept at 40°C. The feed liquid was reacted in the pipeline reactor for 8 hours at a flow rate of 9.0 L / min.

[0034] Pump the reaction feed liquid into the storage tank, add 36% hydrochloric acid (W / V), neutralize the sodium hydroxide in it to near neutrality, add 3‰ activated carbon for needles, stir and raise the temperature to 90°C, and keep it warm for 1 hour, Filtrate through a decarburization filter while hot.

[0035] The filtrate was cooled to 30°C and ultrafiltered through a plate ultrafiltration membrane with a...

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Abstract

The present invention relates to the fields of medicine and chemical industry, and in particular relates to a preparation process for reducing disubstitution proportion of hydroxyethyl starch with middle molecular weight. The preparation process comprises steps of: dispersing amylopectin of suitable molecular weight with purified water; adding a catalyst of sodium hydroxide; respectively carrying out a flow mixing reaction and a flow insulation reaction with an alkylating agent; carrying out decarbonization filtration, ultrafiltration and spray drying on a feed liquid to obtain the hydroxyethyl starch raw material with middle molecular weight. The method can avoid further reaction of the alkylating agent and the generated hydroxyethyl starch, and reduce generation of disubstituted hydroxyethyl starch.

Description

technical field [0001] The invention relates to the technical field of medicine and chemical industry, and relates to a preparation process for reducing the double substitution ratio of medium molecular weight hydroxyethyl starch. Background technique [0002] Hydroxyethyl starch (HES) is a type of colloidal blood volume expander that has attracted the most attention in recent years. To expand blood volume and improve microcirculation. [0003] In 1962, Thompson used hydroxyethyl starch for the first time in clinical practice. After more than 40 years of process improvement, hydroxyethyl starch has gradually become the most popular plasma substitute in European and American countries. In order to reduce the side effects of its clinical application, people continue to optimize its physical and chemical properties. It is found that the weight average molecular weight and molecular weight distribution, molar substitution degree and C2 / C6 ratio are the key factors to ensure the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08B31/12
Inventor 任传杰郑家晴袁洪雨于鹏宋彦会张健
Owner SHANDONG QIDU PHARMA
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