Studies On The Quality Standardization And Preparation Of Rhizoma Corydalis

Rhizoma Corydalis is the dry stem tuber of Corydalis yanhusuo W. T. Wang,which can be traced back to Supplement to the Herbal of the Tang Dynasty. As a traditional Chinese drug,it has been used for the treatment of stagnation of Qi and blood and pains of epigastrium,abdomen and extremity for about two thousand years,because of its acrid flavor and warm nature. As a result of its particular effect, Corydalis DC has been an important subject of the analgesic research.This study is composed of the following six parts:Part 1 Study on the Chemical Composition: From Rhizoma Corydalis,seven compounds were isolated by silica gel chromatography. On the basis of their physical and chemical properties as well as the various spectra data of 1H-NMR,13C-NMR,ESI-MS et al,the structures of the seven constituents were determined,they are d-corydaline(I),tetrahydrocoptisine(II),tetrahydropalmatine(III),tetrahydrocolumbamine(IV),tetraydroberineper(V),protopine(VI) and dehydroglaucine(VII). The purities of compounds I,III,IV and VI can be up to 99%,and they can be used as the reference substance in quality control.Part 2 Research of HPLC Fingerprint: The HPLC fingerprint of Rhizoma Corydalis was established using the gradient elution method,and the results of system suitability test indicated that it had a good precision,reproducibility and stability. Twelve common peaks of the HPLC fingerprint were marked,and eight peaks were identified exactly. 25 batches of samples were determined by HPLC,the results of similarity evaluation indicated that most Rhizoma Corydalis in the market were equal to the reference herb in quality,and they can meet the basic requirements of clinical use. The study revealed that chemical compositions of Rhizoma Corydalis and their relative amount were the key points of quality control. Part 3 Studies on the Technology and Quality of Effective Parts: The effective part of Rhizoma Corydalis was obtained by extracting with 70% ethanol,processing of acidification,alkalization and solvent extraction. The content of total alkaloids in effective part was 63.5% by titration,and the contents of four typical alkaloids (corydaline,tetrahydropalmatine,protopine and tetrahydrocolumbamine) were 13.0%,5.80%,3.63% and 3.85% by HPLC. The quality standard draft of Rhizoma Corydalis effective part was formulated according to the Chinese Pharmacopoeia (2005 edition).Part 4 Fingerprint-efficacy of Rhizoma Corydalis: The result of mice acetic acid writhing indicated that the analgesic activity of Rhizoma Corydalis effective part was quite fair with the medicinal materials. The maximum tolerance dose (MTD) of effective part was about 85mg·kg^-1 and its LD50 was close to 125mg·kg^-1 by mice ig. In the range of 1.6⁴0mg·kg^-1,there was a positive correlation between dosage and effect,and 65mg one day was suggested as the clinical dosage. Analysis of the spectrum-effect relationship shown that Rhizoma Corydalis effective part was composed of the tertiary ammonium alkaloids,which peaks appeared in the region of 30⁷5 minutes on the chromatograph,and the fingerprint of effective part was a good expression of its analgesic activity.Part 5 Study on the Blending of TCM: Under the guidance of fingerprint similarity and on the basis of relationships of Rhizoma Corydalis Fingerprint-efficacy, the optimal and reasonable blending of TCM was proposed, its procedure was as follows:(1)determining the HPLC fingerprints of different medicinal materials;(2)establishing the targets and objects of blending;(3)calculating the optimal prescription/ratio of blending by computer-aided optimization;(4)verifying test. The study indicated that the optimal and reasonable blending basing on the HPLC fingerprint was a scientific and effective way to guarantee the quality of TCM,and met the needs of modernization of traditional Chinese medicine. Part 6 Preparation Research: Modern preparation techniques had been used for preparation research of Rhizoma Corydalis effective part. (1)The solid dispersion of effective part-Poloxamer188(1:4) was prepared in solvent method. (2)The pellets were prepared in a centrifugal granulator by using 5% PVPK30 solution as adhesive agent. The dissolution of pellets was 85% at 10min and was close to 100% in 30min. The pellets had a good performance of immediate release.