| A herbal prescription composed of six Chinese herbs-Cortex Phellodendri, Rhizoma Coptidis, Olibanum, Myrrha, borneol and catechu-has been proved effective in treating columnar ectopy (cervical erosion) by years of clinical application. According to the prescription, patients are required to boil out the herbs and douche vagina by the decoction, the complexity of which, however, has a negative impact on treating effect due to decreased medical compliance. Using modern pharmaceutical technologies, this study carries out some preliminary researches, converting the herbal decoction to proper pharmaceutical preparations so as to both modernize chinese traditional medicine and facilitate administration for patients.Alkaloid substances are active ingredients in Cortex Phellodendri and Rhizoma Coptidis, while catechu contains tannins which will have chemical reactions and generate alkaloid deposit when combined with alkaloid substances, thus interfering in the extraction of effective ingredients from Cortex Phellodendri and Rhizoma Coptidis. This study aims, therefore, to separate catechu from the other five herbs. Catechu is prepared solely as a regular gel (CG), while the other five turn to a thermosensitive gel (TG). A comparative pharmaceutical evaluation of both TG and CG in the treatment of cervical erosion is conducted on the same time.Berberine hydrochloride is the major biologically active substance in Cortex Phellodendri and Rhizoma Coptidis both of which account for the effectiveness of the herbal prescription. In this study, the ultraviolet spectrum and HPLC methods for berberine hydrochloride were established first. The preformulation assay aims to analyze the extraction of berberine hydrochloride in an orthogonal experiment, where three parameters were observed-soaking time, volume of water per time, and boiling time. The research demonstrates that the optimum condition for the extraction were as follows:take Rhizoma Coptidis 20 g, Cortex Phellodendri 10 g, Olibanum 15 g and Myrrha 15 g, soak the herbs in water for 60 minutes, and boil them out for three times (15 min the first,30 min the second, and 2 hours the third with 14 times of water).TG was based on the decoction of the herbal prescription which turns to TG using poloxamer 407(P407) as a matrix. This study observed, first, the function of chitosan to the clarification of the flocculation in the herbal decoction; and, secondly, the impacts of chitosan, P407, PEG 2000 and P188 on the temperature and pH of TG, after a stable and clarified concoction of the herbal decoction was obtained. The results showed that the optimum condition for TG was as follows:pH value of the decoction: 4.6, flocculation temperature:70℃, flocculation time:15 min, concentration of CTS solution:2%, volume of CTS solution:10.0-40.0 ml. Hence, chitosan concoction, PEG2000, and P188 had an obvious impact on the properties of TG. Moreover, the temperature of TG rised with an increase in the amount of 2% chitosan, and the mass fraction of PEG2000 and P188-a positive correlation is hereby observable. The increasing amount of PEG 2000 and P188 did not lead to a significant change of pH in TG which shared the same mass fraction with that of PEG 2000 and P188. Yet the pH in P407-TG changed following an increase in the amount of chitosan. As noticed in further researches on the properties of P188/P407-TG and in vitro, the release rate of berberine hydrochloride in TG was influenced by the erosion rate of gel, both of which comply with zero-order kinetics equation. Hence the concentration of P407 and P188 were the major factors that influence such properties as the temperature of TG, the gel viscosity, the erosion rate, and the drug release rate, etc. Hence, an ideal prescription of TG was as follows:the herbal decoction 50ml, bernol 0.08g,2% chitosan solution 20.0ml, P407 18g, P188 3g, water to 100 ml, Gel temperature 24.0℃. TG could release drug sustainably in body temperature, and the cumulative release in vitro was not completed until about 10.5h later.Catechin and epicatechin are the main biologically active substances in catechu. The HPLC methods for the assay of catechin were established first, together with ultrasonic extraction method to extract effective ingredients in catechu, when concentration, solid-liquid ratio, and extraction temperature of alcohol, and ultrasonic time were used as dependable variables. As demonstrated in the orthogonal experiment, the optimum condition of extraction from catechu was as follows:the solid-liquid ratio 1:12, concentration of alcohol 50%, ultrasonic time 35 min, extraction temperature 60℃.CG was prepared by using carbomer-940 as the gel matrix. In the experiment, the appearance, pH value, and stability of CG was evaluated respectively; meanwhile, the drug release capacity of CG in vitro and the anti-inflammatory effect on big rats were researched on the same time. As shown by the results of the researches, the concentration of carbomer had little impact on the release rate of catechin and epicatechin in vitro. The prescription of CG thus consists of follows:carbomer-940 0.5 g, glycerol 5.0 g, the extracts of catechu 40.0 ml, triethanomine 0.5 ml and water to a total amount of 50 g. CG prepared in this way is fine and clean, semitransparent, sustainable, and quick in drug release in vitro. Hence CG had an obvious effect of suppression on paw edema of big rats caused by carrageenin. Generally, anti-inflammatory function and CG had a positive correlation.Finally, this study conducts further researches on the treating effects of both TG and CG in cervix and vagina of big rats. As shown by the results, a combined application of both TG and CG could effectively cure the experimental cervical erosion of big rats:after taking two units of the medication, pathological changes of vagina and cervix were less serious than those of the model control group, and the bulk of lesion began to recover, even approaching the normal. |
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