Study On Preparation Technology And Quality Evaluation

Resina Draconis is liliaceae dracaena flag leaf dracaena Dracaena cochinchinensis( Lour.) S.C.Chen extraction of resin. With promoting blood circulation to remove blood stasis、anti-inflammatory analgesic、hemostatic effect and so on, the production is mainly used in trauma hemorrhage、injuries、ulcer is not folding of the disease in a wide range of clinical application. Due to Resina Draconis low solubility in water, not easily dispersed in the body after oral dissolution, is limited in clinical use, so it made clathrate, increase its solubility and thus improve the bioavailability, and save the drug resources.After the formation of inclusion, the appropriate method should be adopted, the system of evaluation about the quality of the inclusion compound, to test the rationality of the inclusion process. Inclusion efficiency is an important index to evaluate the quality of the inclusion compound, so should establish complete inclusion efficiency determination method, to make effective evaluation of inclusion. But by direct determination of drug content in inclusion compound, to determine the inclusion efficiency are not folded, adsorption on the surface of inclusion free drug interference, and has yet to see the Resina Draconis inclusion efficiency detection method of inclusion, So this topic first screen separation clathrate and free drugs solvent system, establish the Resina Draconis and measuring method of the inclusion efficiency of inclusion. And for the first time through the qualitative and quantitative indicators, Resina Draconis inclusion quality system is studied. On this basis, the current research to improve the inclusion efficiency more about preparation of inclusion of screening, to add the hydrophilic polymer to improve the method of traditional Chinese medicine the inclusion efficiency of inclusion research is shallow, Therefore, this topic first attempt in Resina Draconis inclusion adding hydrophilic polymers, increase the rate of its inclusion, and optimize the prescription craft.ObjectiveTo establish an method for determination of inclusion efficiency of Resina Draconis inclusion; The index was comprehensive score of inclusion efficiency and yield, use the orthogonal experiment method to optimize preparation process; Through the phase identification, solubility and inclusion constants to evaluate quality of inclusion;Finally, by adding hydrophilic polymer, optimize prescription process of inclusion compound, to explore the feasibility and strategy of the secondary development of products.Method and Result1.Test method for compound inclusion efficiency of Resina Draconis inclusion.Determining Loureirin A content to screening the solvent extraction system of inclusion by HPLC.And Use the method of dosage, polarity and extraction to verify the reliability of the detection method for Resina Draconis incluson inclusion rate. A chromatographic conditions for determining Loureirin A is C18 chromatographic column. The flow rate was 1.0 m L/min amnd the column temperature was 30℃. The mobile phase is 1% glacial acetic acid –acetonitrile(63:37) with sample quantity for 10 μL. The best elution method was 25 m L at a time and eluting 5 times by using ethyl acetate solution. The best extraction method was using 25 m L of methanol solution to ultrasound 30 min in order to validation inclusion rate.2. The screening of preparation technology for inclusionThrough the single factor investigation of inclusion reaction to determine the level range of factors influencing; And Use the orthogonal experiment method to the process factors for saturated water solution to preparate inclusion compound. Select the dosing raio of β-cyclodextrin and Resina Draconis, closure time, inclusion temperature as examine factors.The index was comprehensive score of inclusion efficiency and yield.Then, It got the best preparation process of Resina Draconis inclusion compound. The orthogonal experiment shows that the main factors influencing Resina Draconis inclusion compound is the dosing raio of β-cyclodextrin and Resina Draconis and there was significant differences. The dosing raio of β-cyclodextrin and Resina Draconis for 4:1, closure time for 2 h, inclusion temperature for 60 ℃ is the optimum process conditions of inclusion reaction.3. Phase identification of inclusion compoundBy using scanning electron microscopy, infrared spectroscopy, X-ray diffraction method, UV spectrophotometry and comparing a variety of properties of Resina Draconis, β-cyclodextrin, Resina Draconis inclusion compoundratio and its corresponding physical mixture.It has proved that Resina Draconis and β-cyclodextrin has formed a stable clathrate and verified that inclusion process is a physical function and the elution process of inclusion is reliable.4. The determination of solubility, dissolution rate and constants of inclusionA research on the influence of the solubility for different concentrations of β-cyclodextrin to Resina Draconis, the determination of the solubility of inclusion and the contrast test of dissolution rate before and after closure. The results show that Resina Draconis in ultraviolet spectral absorbance increased with the increasing of the concentration of β-cyclodextrin, the solubility of inclusion is significantly higher than. Resina Draconis.And the dissolution rate and the accumulated dissolution of inclusion is obviously improved.Use phase solubility method to make curve with the molar concentration of Loureirin change with the molar concentration of β-cyclodextrin,to determine the inclusion ratio of the Resina Draconis.Thus, the equilibrium constant of inclusion compound is calculated.The phase solubility diagram shows the inclusion ratio of β-cyclodextrin and Resina Draconis was 1:1, calculating the equilibrium constant K was 506 L/mol.5. Research on optimizing prescription process of inclusion compoundStudy on the effect of CMC-Na and PVP to clathration, and add the PVP clathrate to scan electron microscopy and X-ray diffraction method to identify whether the inclusion is formed.The result shows that the inclusion efficiency decreases with the increase of CMC- Na percentage; inclusion efficiency increased with the increase of the percentage of PVP.It indicates that CMC- Na is not conducive to the formation of inclusion compound, and PVP is helpful for forming inclusion compound. Scanning electron microscopymethod and X-ray diffraction method identify that the PVP clathrate form the stable clathrate.ConclusionThis topic is to establish an HPLC method for determination of inclusion efficiency of Resina Draconis inclusion; Use the orthogonal experiment method to select the best preparation technology of inclusion compound; Through the inclusion efficiency, phase identification, solubilization phenomena,dissolution rate, and inclusion equilibrium constant to evaluate quality of inclusion, it suggests that the solubility in water made a significant increase and effectively proves that the rationality of the inclusion process; By study on optimizing prescription process of inclusion compound, it find that PVP has a effect on improving inclusion efficiency which lay foundation for further optimization of prescription process in Resina Draconis inclusion.