【作者】 赵小燕；

【导师】 田景振；

【作者基本信息】 山东中医药大学 ， 中药学， 2008， 硕士

【摘要】 独一味为唇形科独一味属植物,是我国藏、蒙、纳西等民族习用药材,具有活血止痛,化瘀止血等功能。近年来,藏药备受人们关注,独一味由于其疗效好且迄今未发现毒副作用而广泛应用于临床。独一味总黄酮是独一味镇痛的有效部位,临床可用于治疗骨科骨折引起的疼痛、风湿痛等,还可作为癌痛第一阶梯的止痛药。目前,独一味上市的制剂有胶囊剂、片剂两种。由于崩解缓慢,药物溶出速度慢,且胶囊囊壳容易吸收脱水,导致崩解延长,内容物容易结块,已不能满足临床对药物速效高效的要求。分散片是近年来研究应用较多的一种新的速释固体剂型,具有崩解时间短、分散状态佳、药物溶出迅速、吸收快、生物利用度高;服用方便,既可吞服,又可放入水中冲服,还可咀嚼或含吮,兼具颗粒剂、普通片、含片、咀嚼片的优点,尤其适合老人和吞咽困难患者。本文旨在将独一味胶囊改为分散片,不但可以减少服用剂量,提高药物的疗效,还能丰富临床给药剂型。研究步骤如下:1.本文以独一味总黄酮为指标采用紫外-可见分光光度法进行含量测定,用正交实验优选出了独一味总黄酮的最佳水提工艺。2.研究了大孔吸附树脂富集、纯化独一味总黄酮的工艺条件及参数。以静态饱和吸附量、静态洗脱率为考察指标,对4种大孔树脂吸附和解吸性能进行了比较,结果确定AB-8树脂为研究独一味总黄酮分离纯化工艺最佳树脂。又以总黄酮收率和纯度为指标,对上样液的pH值、上样浓度、吸附速率、水洗用量、洗脱液浓度、洗脱速率、洗脱终点依次进行了考察,确定了最佳吸附和洗脱条件。3.通过平行实验对分散片的辅料进行了选择,筛选出独一味分散片的最佳处方,并确定制备工艺。并通过三批中试对制备工艺进行了验证,结果证明制备工艺简单,适合工业大生产,重复性较好。4.对其质量进行全面考察,初步建立了独一味分散片的质量标准。并分别以正丁醇提取物,独一味总黄酮,木犀草素为指标,对三批中试样品进行含量测定,结果证明该产品质量标准简单可控。5.通过加速稳定性试验及长期稳定性试验证明该样品稳定性良好。6.应用小鼠热板法、醋酸扭体法、小鼠二甲苯耳肿胀法、小鼠断尾出血法对独一味分散片进行初步药效学研究,试验表明独一味分散片具有较好的镇痛、抗炎、止血作用,而且,毒性甚微,安全性高。总之,本研究表明,独一味分散片制备工艺简单,质量标准简单可控,适合工业大生产,临床药效确切,服用量低,生物利用度高,服用方便,具有广泛的开发应用前景。更多还原

【Abstract】 Lamiophlomis rotata Kudo belongs to Lamiophlomis rotata Kudo genus is a popular national folk herbal medicine in China’s Tibetan,Mongolian,Naxi and other nations.It can be used to promot blood flow, relieve pain , remove blood stasis , hemostasis and so on .In recent years, it has more people’s attention.Now it is widely used in clinical because of it has many good effects and have no toxic side effects. Duyiwei total flavonoids is the effective analgesia site of Lamiophlomis rotata Kudo, can be used for clinical treatment of orthopedics fractures caused by pain, rheumatism pain,the first step pain medicine for cancer and so on.At present,Lamiophlomis rotata Kudo has only capsule and tablet on the market.Now they have can’t meet the clinical requirement for immediate effects and high performances,for the collapse and dissolution is slow, capsule shell is easily dehydrates for absorption extend the rate of collapse.In recent years,dispersible tablet is a new fast-release solid dosage form,has many good qualities,better decentralized state,shorter collapse time,rapider dissolution,faster absorption,bioavilability and it is easy to take ,can be swallow ,drink with water and chew,so it is popular with elderly patients and patients with dysphagia. The research to change Duyiwei capsule to dispersible tablet can reduce dosage,increase drug action and rich dosage form.The procedure will be describe as follows.1.Determine the content of Duyiwei total flavonoids by ultraviolet- spectrophotometer.The optimize water extract processing were selected by orthogonal experiment. 2.Use macroporous resin to rich and pure Duyiwei total flavonoids,and get the process condition and parameters.Through study the absorption and desorption properties of the four kinds of macroporous adsorptive resin with static absorption capacity,static indicators washout rate,the AB-8 determined as the best resin to separation and purity the total flavonoids.Through study the sample pH value,sample concentration,adsorption rate,washed dosage,elution concentration,eluate rate and the end of elution ,the optimize absoption and desorption condition were determined.3.Flit the Duyiwei dispersible tablet optimize prescription and determine the prodution technology by choose the accessories with parallel experiment. Verify the prodution technology is easy,suitable for industrial production and have good repeatability by three batches experiment.4.Establish the Duyiwei dispersible tablet quality standard by inspect the quality.The production quality standard is proved easy to be controlled by determine the content of Duyiwei total flavonoids and luteolin by three batches experiment.5.The quality standard were proved Duyiwei dispersible tablet have good stability through determine content of sample by accelation stability and long-term stability experiment.6.The pharmacodynamics study of Duyiwei dispersible tablet showed it has good analgesic and anti-inflammatory roles and hemostasis and have minimal toxicity through mouse hot plate,acetic acid writhing law and xylene mouse ear swelling and mouse tail bleeding experiment.On the whole, Duyiwei dispersible tablet has a good development and application perspect for it is suitable for industrial production, controllable in quality standard and have precise drug action,low dosage,high bioavilability.更多还原