Study On The Key Influencing Factors Of The Synthesis Process Of Iron Sucrose Complex

Iron is involved in many biochemical reactions,including oxygen transport and storage,DNA synthesis,adenosine triphosphate production and electron transfer,and it is one of the most important minerals in the human body.If the body is deficient in iron,it can not meet the needs of normal red blood cell production,it will directly lead to iron-deficiency anemia（IDA）.IDA,caused by nutritional deficiencies and blood loss,remains the most common and treatable form of anemia in the world.Traditional drugs for the treatment of iron deficiency anemia are mainly inorganic iron supplements and soluble small molecule organic iron salt iron supplements,which are generally used for oral administration,however,they have side effects on the gastrointestinal tract irritation and a series of adverse reactions and poor digestion and absorption of iron.Macromolecular iron sucrose complex can be prepared into an injection preparation for intravenous administration to overcome the above disadvantages.It can overcome the shortcomings of low intestinal absorption and the long course of oral iron treatment and most of the gastrointestinal reactions,which can meet the needs of rapid iron supplementation and alternative blood transfusion.It is mainly used for patients whose oral iron is not easily absorbed and cannot be tolerated.The purpose of this paper is to study the preparation process of iron sucrose complex（ISC）.It is mainly divided into three steps:the first step is the synthesis of ferric hydroxide colloidal slurry by chemical reaction of ferric salt（FeCl₃·6H₂O）under the conditions;The second step is to chelating the inorganic ferric ion in the synthesized iron hydroxide colloid slurry with sucrose to obtain a macromolecular iron sucrose complex;The third step is to separate and purify by organic solvent precipitation.Because the preparation process of ISC is more complicated and has many influencing factors,the preparation process is optimized by single factor method and response surface method respectively.The yield and weight-average molecular weight（Mw）were weighted to identify the most influential factors and screen out the best process conditions.In the first part,through single factor method,the yield of ISC is taken as an indicator to find out the factors that have a great influence on the yield.secondly,gel permeation chromatography（GPC）was used to establish a standard curve of the retention time and molecular weight of dextran standard solutions of different molecular weight.The calibration curve was used to calculate weight-average molecular weight of ISC.through single factor method,the weight-average molecular weight of ISC was taken as an indicator to investigate the influence factors and placement time of the ferric hydroxide in the first step on the molecular weight of the final product.Thirdly,based on the single factor experiment,the reaction temperature,reaction time,amount of alkali,and amount of sucrose of ISC were selected as the investigation factors in the second step.The weight average molecular weight of ISC was determined by GPC.As an indicator of the evaluation,the synthesis process of ISC was optimized by the response surface method（RSM）of the Box-Behnker central composite design.Secondly,the reaction temperature,amount of the first base（30%Na₂CO₃solution）,pH of termination were taken as the factors in the first step to optimize the synthesis process of ferric hydroxide by the same method.Finally,it mainly clarifies the state of ISC and other characterization,such as scanning electron microscopy（SEM）,powder X-ray diffractometry（PXRD）,atomic absorption spectrometry（AAS）,etc.It proves that the ISC solution is a brown-black colloidal solution,the solid form is an amorphous,brown powder,and it is tasteless and soluble in water.ISC has an iron content of 26.7%,which is consistent with the morphology reported in the literature.Based on the above results,we can conclude that neither the first step nor the second step temperature and pH have a significant effect on the ISC weight-average molecular weight,which should be strictly controlled during the experiment.Temperature and pH are the key factors for the catalytic reaction.