Application Research On Near Infrared Spectroscopy In Critical Quality Control Links Of Chondroitin Sulfate

Chondroitin sulfate (CS) is an anionic linear polysaccharide which is composed alternatively by D-glucuronic acid and differently sulfated residues of/V-acetyl-D-galactosamine linked by β(1-3) bonds and it mainly exists in extracellular matrix of articular cartilage.The diversity of chondroitin sulfate makes chondroitin sulfate have a lot of biological information, which could affect manybiochemical processes.Thus, chondroitin sulfate have a wide range of applications in clinical.The production of Chondroitin sulfate including the whole processesfrom raw materialto product storage.It generally refers to the evaluation of raw materials, chondroitin sulfate extraction, ultrafiltration, oxidation, ethanol precipitation, drying, grinding, packaging and a series of unit operations. Differences in the quality of raw materials and fluctuations of process parameters will lead to an unstable product quality and differences between batches. Therefore, development of an effective rapid test method is particularly critical.Under this consideration,this thesis selects chondroitin sulfate powder and unit operation of ethanol precipitation as research object.Chondroitin sulfate sources identification and content determination models were optimized.Water content and multivariate statistical process control model in ethanol precipitation process were established.The details are listed belows:Firstly, we optimized the model for identifying the sources of chondroitin sulfate, the predictive ability was improved.The rate of recognition and rejection was100%.Secondly, we used test sample and actual sample to configure a certain gradient of chondroitin sulfate content of solid powder. The diffuse reflectance spectra of samples were associated with chondroitin sulfate content using PLS method. Useful variables were selected using iPLS method, GA and CARS-PLS method.Thirdly, we use a method to configure a certain gradient of water content in chondroitin sulfate solid powder.The diffuse reflectance spectra of samples were associated with water content in chondroitin sulfate using PLS method. Useful variables were selected using correlation coefficent method, iPLS method and CARS-PLS method.The first part is to establish an in-line monitoring model to make a better understanding of the precipitation process.6batches of NIR spectra were collected, and the first, second and third batches were used to establisha model. The remaining batchese were used to validate the model. The fourth and fifth batches maked by unnormal operations were used to validate the model, and the sixth batch was a nomal batch. The second part is to establish a PLS model to predict the chondroitin sulfate content in the precipitation process.5batches of chondroitin sulfate mother liquor were collected under the same ethanol precipitation conditions, and the transmission spectra were associated with the chondroitin sulfate content which was determined by sulfuric acid carbazole method. A PLS model was established to predict the content in mother liquor.