Process Optimization And Process Control About Hydroxyethyl Starch 130/0.4

Hydroxyethyl Starch (HES) is a fine plasma substitutes that are mainly used for the clinical for haemorrhagic shock, traumatic, infectious and toxic shock treatment. The first series of hydroxyethyl starch that is 40,20 series, are firstly developed in our country.We usually name them "706 plasma substitute", due to its low molecular weight and volume expansion effect of plasma.Recently, they are gradually replaced by hydroxyethyl starch 130/0.4. Hydorxyethyl Starch 130/0.4 is the third generation HES product which is developed in the United States.successfully. Owing to the medium molecular weight and low degree of substitution, the effectiveness and security are improved significantly and they are usually used as main blood substitute in great demand. Currently, the products depend on imports in our contry, resulting in a substantial burden on people's drug use. Therefore, our team cooperated with enterprises, researched the production engineering and the qualitu control of hydroxyethyl starch 130/0.4 to achieve a mature production technology.Firstly, We built the quality control method using HPGPC to determine the molecular weight and distribution of its molecular weight. The chromatographic conditions:the mobile phase was 0.6% sodium sulfate; column temperature was 35℃; the flow rate was 0.5 ml-min-1; The mobile phase refractive index was 1.334; dn/dc was 0.135 ml/g; The second virial coefficient A2 was 10-4 moL·ml/g. The results showed that the method was efficient, simple, specific, and had a good sensitivity, recovery and reproducibility. We determined the molar degree of substitution of hydroxyethyl starch 130/0.4 using GC. The chromatographic conditions:the chromatographic column was CP-Si15CB (100% polydimethylsiloxane; 25m×0.25 mm, DF= 0.4μm); the detector was FID; the carrer gas wass helium; the flow rate is 1 ml-min-1; the injection volume is 1μl; the injector temperature was 290℃; the detector temperature was 290℃and the split ratio was 1:20. This method were provided with high separation, efficiency and specificity, so it could be used as the method to determine the molar degree of substitution. Meanwhile, this paper used GC-MS to confirm the structure of the product and the ratio of C2/C6 was 9.6,which meet the requirements.Secondly, we studied the preparation technology. By controlling the process of hydroxyethyl key process parameters, a mature production process route was developed. We made a comparison between IR spectra on the molecular weight, the molecular weight distribution, the molar degree of substitution, the substitution position and other indicators with the imported products of Germany. The results revealed that the product and the German Fresenius(Wan-Leste) product had no significant difference in the preparation process to further validate the reliability and feasibility.