| Chinese Medicine formula granules are made using high quality Chinese medicine through modern pharmaceutical technology. These granules provide the same effects as Chinese traditional herbal medicine (without having to boil the medicine). Additionally, the granules are easy to adjust, simple to use and can be effortlessly controlled. With an annual output value of billions of Renminbi, Chinese Medicine formula granules are widely used in more than2,000hospitals and are exported internationally. The advance in technology has created good social and economic benefits.Owing to the changes in the environment where herbs are planted, imperfect quality control standards in Chinese Medicine, deteriorating quality of Chinese Herbal Medicine, the subjective description of quality control for Chuanwu in the Pharmacopoeia; lack of on-line control of industrial production; formula granules does not have the original appearance. Traditional detection method is over complicated and restricted by modern industrial ized production.This subject started from dealing with standardized concoct and examines the variation of each process system. Chuanwu ingredients, combined with high performance liquid chromatography (HPLC) and near-infrared spectroscopy (NIR), established NIR models aid to analyse the content to control the process. Then, particles of the Chuanwu recipe are linked in the production process and are monitored and optimized. Particle production process parameters are combined with pharmacological and toxicological experiments. Chuanwu concocted recipe particles are the best technology to date, and to develop relevant standards, provide trustworthy experimental basis for standardized production. The main conclusions are as follows:1. Use NIR to collect the data of119Aconiti Radix Cocta samples, use partial least squares regression(PLS) method to establish quantitative analysis model of monoester alkaloids, diester alkaloids and moisture between the information of NIR and HPLC. The spectral ranges of monoester alkaloids, diester alkaloids and moisture models of Aconiti Radix Cocta are;8431.26-4075.93,5086.76-4088.64/7725.44～5924.25and7934.87～4088.64cm-1. The root mean square errors of calibration (RMSEC) and correlation coefficient (r) of the calibration models are; RMSECmonoester alkaloids=0.098, r monoester alkaloids=0.9559, RMSECdiester alkaloidS=0.034, r diester alkaloid=0.9694and RMSEC moisture=0.002, r moisture=0.9767. The root-mean-square error of prediction (RMSEP) and r of the validation models are; RMSEPmonoester alkaloids-0.168, r monoester alkaloids=0.9266, RMSEP diester alkaloids=0.039, r diester alkaloids=0.9826and RMSEP moisture=0.004, r moisture=0.8363. According to the results of statistical tests, r between the predicted value and the reference value of the three types of ingredients are;0.970,0.993and0.918, P<0.001. This means that to analyze these compositions the method of NIR is as good as HPLC and the dehydration method (for testing the value of moisture) of the pharmacopoeia requirements.2. Using NIR to collect the data of103samples and using PLS method to establish the quantitative analysis model of monoester alkaloid in the information between NIR and monoester alkaloid. The spectral range of monoester alkaloids model is9264.35～7274.11cm-1. The root mean square error of cross validation RMSECV=1.171and r calibration model=0.9994. Through the external validation, RMSEP=1.321and r validation model=0.9921. According to the results of statistical analysis, r of the predicted value and the reference value of monoester alkaloids is0.999, P<0.001. This revealed that the NIR and HPLC methods have a good correlation in determining monoester alkaloids and accurately predict the amount of monoester alkaloids in the covered range.3. Use content of6Alkaloids compositions of Aconiti Radix as the evaluation index to do single factor experiments to examine factors of soaking, steaming and drying conditions. The result of the best processing technology is; soak Aconiti Radix in40℃water for25±1h, high pressure steam(111℃) for1h, dry at60℃to obtain diester and monoester alkaloid content of the pharmacopoeia requirements. After concocting15～150min in111℃(0.05MPa), the content of diester alkaloid in Aconiti Radix Cocta in the relation curve fitting regression equation was C(mg/g)=0.273+0.236X In t (min)(R2=0.753, F=48.818, P<0.01), monoester alkaloid was C(mg/g)=0.115×t-0.005(min)(R2=0.850, F=90.660, P<0.01).4. According to single factor tests and the Orthogonal Test Design, Aconiti Radix Cocta formula granule’s best process in extraction is; add10times amount of water, extract three times, each time for2hours. The best process in concentration is; concentrate under reduced pressure by75℃. To achieve the best drying process; materials’relative density of1.10(60℃), inlet air temperature of165℃and air-out temperature70℃by spray drying. To achieve a solid form; put extract powder (moisture3-4%, spray little amount of95%medicinal alcohol in granulation process) into dry type granulator, control roller pressure as0.3-0.35Mpa, side sealing pressure as0.05-0.06Mpa, grade with12mesh sieve, take No.1-4sieve as qualified granule.5. The finishing point of the concocting process is when the content of monoester alkaloids is around1.400mg/g, and diester alkaloid is around0.100mg/g. According to the statistical correlation analysis by SPSS15.0, rbetween predicted value and reference value of monoester alkaloid is r monoesler alkaloid=0.991, diester alkaloid is r diester alkaloid=0.998, moisture is rmoisture=0.958, P <0.001. The finishing point of extracting process is when the content of monoester alkaloids is first time of102～105μg/L, second time by37μg/L, third time around16μg/L. During the extracting process, r monoester alkaloids=0.999, P<.0.001. The finishing point of concentration is when the content of monoester alkaloids is156～159μg/L. During concentration process, rmonoester alkaloids=0.999, P<0.001. During the drying process, r monlester alkaloid=0.901, r moisture=0.880, P <0.001. During the forming process, r monlester alkaloid=0.957,rmoisture=0.961, P <0.001. The data above shows that the correlation between predicted value and reference value is good, and NIR can be used for rapid detection of the preparation of Aconiti Radix Cocta formula granule.6. The toxicity studies on Aconiti Radix Cocta formula granule shows that Aconiti Radix Cocta formula granule is safe under the highest concentration (150.00g medicine/kg). During the dimethyl acetic acid body turning text, the turning frequency between traditional form group and formula granule group is similar-both are less than model group. While latent time in traditional form group and formula granule group are longer than model group. The formula granule group got closer to Fenbidand better than the traditional form. During the auricular inflammation test, when the mice ear swelling rejection rate was between22.51～38.65%, the effect of1/2,1,2times of the clinical equivalent dose (195,390,780mg/kg) are equal to0.07,0.20,0.46times of Aconiti Radix Cocta formula granule (27.36,77.67,178.29mg/kg), DEEformula granule (mg/kg)=-22.950+0.258×DEEtraditional from(mg/kg)(R2=0.958, r=0.979, P<0.01), b0=-22.950,95%confidence interval is (4.549,41.351)(P<0.05), b1=0.258,95%confidence interval is (-0.218,0.299)(P<0.05). Hence, the dose of equivalent effects of Aconiti Radix Cocta formula granule is less than the traditional form. When the clinical equivalent dose of1/8～1times, EED formula granule(%)=2.963+1.573×EEDtraditional form(%)(R2=0.923, r=0.961, P<0.01),b0=2.963,95%confidence interval is (-5.373,11.300)(P<0.05), b1=1.573,95%confidence interval is (1.230,1.915)(P<0.05). Thus, the effects of the equivalent dose of Aconiti Radix Cocta formula granule is stronger than the traditional form. |
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