Preparation And Quality Study Of Polysaccharide Peritoneal Dialysis Solution

Peritoneal dialysis(PD)is a new type of renal replacement therapy after the hemodialysis,which is as an effective way of treating end-stage renal disease(ESRD)after kidney transplant,and also be used in the treatment of heart failure(HF)and acute hemorrhagic necrotic pancreatitis(AHNP),etc.The treatment mechanism of PD is to remove toxic metabolites in the blood by peritoneal ultrafiltration,such as creatinine,urea nitrogen,tumor necrosis factor,interleukin,over loaded fluid and salt ions,etc.To remove toxic substances and over loaded water and salt,toxic metabolites are permeated into the peritoneal cavity from the blood in the aid of osmotic pressure.Water can also be transported into the peritoneal cavity by the activation of the water channel protein in the surface of the mesothelium cell or under the action of colloid osmotic pressure.The waste materials are poured out through the drainage system and reperfused in a certain period of time,and the cycle repeats.Currently,there are two types of peritoneal dialysis solution being used clinically.The first one is a small molecule osmotic solute peritoneal dialysis solution,such as glucose lactate and amino acid peritoneal dialysis solution.Glucose lactate peritoneal dialysis solution has been marked in China with a generic drug standard;Amino acid peritoneal dialysis solution was not registered in CFDA.The advantage of amino acid dialysis solution is to supplement human nutrition and adjust negative nitrogen balance into a positive nitrogen balance at long-term peritoneal dialysis.The second type is macromolecular peritoneal dialysis solution.For example,Icodextrin can solve the problem of ultrafiltration failure,which was unlisted in domestic market.This thesis is mainly to study the preparation of polysaccharide active ingredient and pHarmaceutics and the quality.Icodextrin is prepared with the hydrolysis of starch,according to icodextrin specification.Starch raw material is commonly waxy corn starch with high branched degree.In order to meet the demand of colloid osmotic pressure,the hydrolysis condition of temperature,acidity and time were studied,which was monitored with polysaccharide molecular weight by the gel permeation chromatograpHy(GPC).Insoluble polysaccharide in the hydrolysis solution was removed through filtration and then refined by ultrafiltration with membrane with a cut-off=3000 Da to obtain purified polysaccharide with homogeneous distribution of Molecular weight.Freeze drying was used to obtain the final product.In the early-stage study of the preparation,there was chlorine residual in the process of starch hydrolysis with hydrochloric acid.Dialysis,ion exchange and ultrafiltration were used to remove chloride and lowered the chloride level under 50 ppm.In the study of the quality of polysaccharides,quantitative nuclear magnetic method and optical rotation were used to determine the amount of polysaccharide and then the feasibility of methodology is validated;the traditional titration method and atomic absorption spectral spectrum method is used to receive the peritoneal dialysis fluid content of metal ions.Single standard calibration and wide standard calibration was used to study the polysaccharide molecular weight distribution with gel permeation chromatograpHy.