Traditional Chinese Medicine Preparation Process Of Any Substantive Changes In The Early And Rapid Detection (i),

Whether there are qualitative changes in the processes of Chinese drug preparation or not is a key technical indicatio that widely puzzled drug evaluation and R&D personnels for several years. In all the processes of Chinese drug preparation, the quality of products would be influenced by the change of preparation. The different extractive solvents and technical lines are usually regarded existing qualitative changes, while the processes of concentration, drying and shaping are usually regarded no impact to the quality and drug action of products, or ignored for the lack of sensitive and volant detection methods.In this paper, we selected Radix isatidis as a mould, a traditional Chinese medicine whose therapeutic effects are approved, but the active substances are not so clear that there are difficulties in its quality control. Drying processes were the researching object. The conventional physico-chemical properties of products were determined as well as the thermal analysis graph, the contents of chemical index constituents, the similarity of fingerprint (FP) and the biothermodynamic indexes through some special kinds of methods in sequence. Then the results were analysed statistically, by which the similarities and variabilities of different products could be described qualitatively and quantitatively. Therefore the extent and quality of the change of drying process could be evaluated, the drying condition could be optimized, the quality and drug action of products could be guaranteed. Rapid detective methods and evaluative mode for the qualitive change of Chinese drug preparation were preliminarily established. Results as following:1. Four different kinds of drying products(about 40 batches in total), such as spray drying, freeze drying, vacuum drying and drying under normal pressure, were prepared before analysis. The conventional physico-chemical properties (CPCP) of products such as colour, trait, diffluence, moisture, critical relative humidity(CRH) and value of pH were determined preliminarily and compared between groups. There existed great differences in different samples. These methods were convenient but greatly impacted by subjective factors.2. Thermal analyses (TA) such as TGA (thermo-gravimetric analysis), DTA (differential thermal analysis) and DSC (differential scanning calorimetry) were carried out. The TGA curves were similar as they were all typical slowly breakdown process curves. There were three characteristic periods in which the weight loss of the four kinds of products had evident differences(RSD>20%)(n=4), especially in the first period(135℃～165℃)(RSD=78.41 %)(n=4). So DTA would be a useful method to detect the objectivity of different drying process. This method had the characters of objective, direct-viewing, fast and good entirety, but had difficulties to describe the changes of chemical compositions concretely.3. The contents of chemical index constituents such as benzoic acid, salicylic acid, adenosine were determined by HPLC, while the contents of polysaccharides by UV-VIS. The results were compared by the single factor K level (K≥3) multivariate analysis. There were significant differences (P<0.01) between every two groups. And the similarities of FP were also determined. All the samples had high similarities of more than 0.92. It also showed significant differences (P<0.01) between every two groups by single factor K level (K≥3) analysis of variance. So FP combining with content determination (CD) would be a useful method to detect the objectivity of different drying processes. The method had the characters of direct-viewing, precise, and could partly reflect the changes of material foundation, but had the limit of correlation with activity when the active substances were not clear.4. The biothermodynamics (BTD) graphs were detected by microcalorimetry (MC) when samples were added into the culture medium where the Escherichia coli lived. Then the BTD parameters such as k\ (the 1st growth rate constant), k₂ (the 2nd growth rate constant), P_m² (the 2nd maximum power) and T_m² (the 2nd maximum power time) could be calculated. There were significant differences(P<0.01) between every two groups except spray drying and freeze drying by the single factor K level (K≥3) multivariate analysis according to the BTD parameters. So BTD would be a useful method to detect the objectivity of different drying process. The BTD method had the merits of rapid, accurate, sensitive, convenient and could be correlated with activity, but the selectivity and specificity of the method were not so good.5. Early, rapid detection methods system of qualitive change of Chinese drug preparation based on CPCP-TA-CD-FP-BTD in sequence were proposed and preliminarily established for the first time. We evaluated the different drying process of the decoction of Radix isatidis by these methods. The rudimental conclusion was that spray drying had little difference with freeze drying while there were large differences between other drying processes. This conclusion needs to be confirmed by further pharmacologic and clinical therapeutic experiments. 6. According to the researches above, the best drying condition and parameters of Radix isatidis decoction to be prelimilarily sured was spray drying with a relative density of material of 1.15, an inlet air temperature of 180℃, an outlet air temperature of 90℃.