| Objective:To research the preparation process, quality standard of Fufang Jinlingsinisiwushixiao Granules and lay the foundation for the quality control. The acute toxicity of the medicine was investigated to evaluate the safety of clinical applications. Under the guidance of the theory "Prevention before Disease Onset", the pharmacodynamics was studied.Methods:1. In the study of the preparation process, the single factor test and orthogonal approach of L9 (34) was applied, and multi-index comprehensive evaluation method was used, the best extraction technology by ethanol and water were determined, the optimum extraction conditions and the optimum preparation conditions of voliate oil were discussed. In addition, the best molding process was selected.2. The thin chromatography identification of Radix Paeoniae Alba, Rhizoma Corydalls and Radx angelica and the determination of content of paeoniflorin was stabled in quality standard.3. On the pharmacodynamics experimental study, the maximum tolerated dose (MTD) was determined on mice by oral gavage. Rats dysmenorrheal model was induced, using the method of pre-medication, the contents of β-EP in the blood and PGF2α, PGE2,6-Keto-PGF1α and TXB2 in uterine tissue were observed simultaneously by the medicine, so that clear the mechanism of the medicine.Results:1. The optimum preparation process is confirmed as follows:Extract Radix Paeoniae Alba, Rhizoma Corydalls and Melia Toosendan for 3 times under reflux with 8 times the amount of 70% ethanol for 1 hour, the ethanol extraction solution is concentrated under reduced pressure to dense extractum. Extract volatile oil from Radix angelica, Bupleurum, Fructus Aurantii and Ligusticum chaunxiong for 8 hours after the material shattered into 20 meshes with 8 times the amount of water. The volatile oil was included with HP-β-CD, the proportion of 1:6 (volatile oil and HP-β-CD), inclusion temperature of 30℃ and grinding time of 1 hour. Remaining crude materials are extracted for 3 times under 10 times the amount of water for 1 hour, water extraction solution which is concentrated into l:1.3(crude material to volume),then add 70% ethanol to purify to obtain the total polysaccharides extraction. At this moment,we commix the ethanol extraction dense extractum, the total polysaccharides extraction with volatile oil extraction solution, drying them into dry extract powder under vacuum. The dry extract powder is mixed with starch and microcrystalline cellulose (the proportion of 2:1:1), using 85% ethanol as wetting agent to preparate granules, then sieving and 60℃ drying that mixed with volatile oil inclusion.2. We have established the thin chromatography identification of Radix Paeoniae Alba, Rhizoma Corydalls and Radix angelica and the determination method of content of paeoniflorin was stabled in the quality standard.3. Pharmacodynamics experimental study manifest that Fufang Jinlingsinisiwushixiao Granules is of low acute toxicity to mice, and the maximum tolerated dose is 192 g·kg-1 on mice, which is equivalent to 217.4 times of the clinical dose. The medicine has a significantly analgesic effects on dysmenorrheal rats with dose-dependent relation that through evidently increasing β-EP in the blood and PGE2、6-Keto-PGF1α in uterine tissue, decreasing PGF2α、 TXB2 in uterine tissue obtain the cure effect.Conclusion:The quality of the preparation is better and stable with the optimized technology that is feasible. The determination methods in quality standard is accurate and high specific that can control the quality effectively. Pharmacodynamics experiment show that the clinical prescribed dose of the medicine is in a high safety and has obvious effect of invigorating the circulation of blood, dispersing blood stasis and relieve pain. |
PDF Full Text Request