| Objective:Bronchial Asthma is a kind of common ailment and frequently encountered disease. According to the epidemiological survey, in recent years, with the influence of environmental pollution problems, asthma has an obvious rising trend of morbidity and mortality, and gradually become a dangerous "killer" to human health. Anti-asthma dripping pills of compound earthworm is made up of three Chinese medicine called ephedra, liquorice and lumbricus, and usually used in the treatment of allergic asthma. In this paper, we investigated the preparation technics of anti-asthma dripping pills of compound earthworm. Firstly, we completed the optimization of the traditional extraction technology of ephedra and liquorice; then, we study on the preparation of anti-asthma dripping pills of compound earthworm, investigating the quality evaluation indices such as the difference of weight, the time-limit of dissolution, and etc., and finally, a preliminary pharmacodynamics experiment was conducted so as to provide the theoretical basis for the further in-depth development of anti-asthma dripping pills of compound earthworm.Methods:1.Study on the extraction technology of ephedra, liquoriceIn order to completely extract the effective substances in ephedra, liquorice, the current extraction methods were improved. By using L9(34) orthogonal design method, we investigated the effects of water added in extraction, extraction time and times of extraction on the refined extraction, and in doing so, to determine the optimal extraction technics of ephedra and liquorice.2.Study on the preparation technology of anti-asthma dripping pillsThe solid dispersion technology was employed in the preparation of the dripping pills. Single-factor experiments were done to determine the effects of the dripping matrix, the class of condensate, the optimal temperature of condensate, the dripping speed and the dripping distance on the formation of dripping pills. By using L9(34) orthogonal design method, we optimized the preparation technics of dripping pills based on the evaluation on the effects of the factors as the ratio of matrix, the ratio of drugs and matrix, and the dripping distance on the evaluation indices as the appearance quality of the dripping pills, the timelimit of dissolution and the variation coefficient.3. The preliminary study on the quality standards of anti-asthma dripping pillsThin layer chromatography(TLC) method was employed to qualitatively identify ephedra, liquorice and earthworm in the anti-asthma dripping pills. High performance liquid chromatography(HPLC) technique was adopted to establish the content determination method for ephedrine hydrochloride, glycyrrhizic acid and hypoxanthine in the pills. The weight variation and the time-limit of dissolution of the anti-asthma dripping pills were examined in accordance with the regulations in the appendix of "Chinese pharmacopoeia" 2010 edition.4.Study on the pharmacodynamics of anti-asthma dripping pillsTo investigate the effect of anti-asthma dripping pills on the acute asthma model of guinea pig established by using histamine, acetylcholine chloride and ovalbum(OVA).Results:1. Study on the extraction technology of ephedra, liquoriceEphedra 100 g, added 15 times amount of distilled water and soaked for 30 mins, and then extracted by heat. 20 mins later, added 50 g of liquorice and 750 ml of distilled water, and continued heat extracting for 90 mins. Then, poured liquid to filter, the remaining residue was filled 15 times distilled water and continued the second extraction. So after three times, the filtrate was merged. In the next step, firstly by using the vacuum suction on the filtrate, the bulky residue was filtered, then using the negative pressure rotary evaporation instrument to enrich the filtrate to 150 ml of liquids, with concentration of 1g/ml. Based on this method, three times of extraction experiments were done respectively, and the extratum got a quantity of around 23.4 g, extraction yield of around 59.8%.2. Study on the preparation technology of anti-asthma dripping pillsThe final optimal technics of preparation of the dripping pills is as follows: Condenser pipe of a total length of 100cm; Liquid temperature of 60 ℃; Using simethicone as condensate; Temperature at the bottom of the condensate was 4(±2)℃, 20(±2) ℃ at the top; PEG4000:PEG6000 was 1:3 and Drug:substrate was 1:4; The dripping distance was 5cm and the speed was 15 drops/min. Based on these optimum conditions, 3 batches of dripping pill samples were prepared. The anti-asthma dripping pills had smooth faces and uniform colour of yellow brown. The pill weight variation coefficient was 3.85%~4.62%, with the time-limit of dissolution within the range of 5.3 ~ 9.7 min, and the appearance quality was good.3. The preliminary study on the quality standards of anti-asthma dripping pillsIn ephedra, liquorice and lumbricus TLC identification experiments, the sample’s chromatography showed the same color spots in the corresponding position with the control chromatography. These TLC spots were clear and the negative control had no interference. The anti-asthma dripping pills weight difference and time-limit of dissolution conforms to the quality requirements for dripping pills in Chinese Pharmacopoeia 2010. In the content determination experiment, ephedrine hydrochloride had a good linear relation in the concentration range of 7.8~78mg/l, with R2=0.9998(n=5), the average sample recovery rate of 100.09%, and RSD of 0.30%. Glycyrrhizic acid had a good linear relation in the concentration range of 21.6~216mg/l, with R2= 0.9997(n=5), the average sample recovery rate of 100.10%, and RSD of 0.46%. Hypoxanthine had a good linear relation in the concentration range of 1.75~21.5mg/l, with R2= 0.9997(n=5), the average sample recovery rate of 98.71%, and RSD of 1.57%.4. Study on the pharmacodynamics of anti-asthma dripping pillsLow and high content of dripping pills could notably prolong the incubation period of asthma(p<0.05) and reduce the number of fall of the histamine – induced model guinea pigs within 6 minutes, and also extend the incubation period of asthma guinea pigs by using OVA sensitization and reduce the asthma mortality rate.Conclusion:The technology of solid dispersion was employed for the preparation of anti-asthma dripping pills. The extraction process of ephedra, liquorice was optimized to effectively increase the extraction yields. The developed preparation technics could produce dripping pills with stable quality and reproducibility. The quality standard method for dripping pills was set up with high sensitivity, good accuracy and specificity and good reproducibility. Pharmacodynamics research on the dripping pills of compound earthworm also proved the anti-asthma effect. |
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