抗病毒滴丸的研制

【作者】 金京龙；

【导师】 崔东滨；

【作者基本信息】 延边大学 ， 药物化学， 2007， 硕士

【摘要】 抗病毒胶囊由板蓝根、石膏、生地黄、广藿香、连翘、芦根、郁金、石菖蒲、知母9味组成，收载于部颁标准新药转正标准第7册，具有清热祛湿、凉血解毒之功效，对治疗流感、风热感冒、上呼吸道感染等病毒性疾病具有很好的疗效，但胶囊剂存在服用量大且药效发挥较慢的不足，我们在药理实验的基础上，将抗病毒胶囊的粗提物进行精制，减少服用量，制成具有起效快、生物利用度高的滴丸剂。本论文对其制备工艺、质量评价、生物学评价、初步稳定性进行了深入研究，具体方法及结果如下：首先根据处方中各种药材所含有效成分的理化性质和药理作用，确定了合理的工艺路线。采用单因素试验和正交试验法优选确定了处方中广藿香、石菖蒲、郁金的挥发油提取工艺，连翘、知母的醇提工艺及板蓝根、石膏、生地黄、芦根的水煎醇沉工艺，确定了药味粗提物的制备方法并将其制成干浸膏粉。以药效实验为考察指标，对处方中药味粗提物进行精制，制得抗病毒有效部位。以圆整度为考察指标，采用单因素考察和正交设计试验，筛选出合理的滴丸成型工艺条件。结果采用90％乙醇温浸对粗提物进行精制，制得的有效部位药效明显优于原胶囊。以PEG4000∶PEG6000(1∶1)混合作为基质，二甲硅油为冷却剂，药物与基质以1∶3配比，料温为80℃，冷却温度为5℃，滴口内外径为2.0／2.4(mm／mm)，滴口距冷却液面为4cm，滴速30d／min为最佳滴丸成型工艺。在抗病毒滴丸的质量评价研究中，采用薄层色谱法对制剂中板蓝根、知母、连翘、广藿香进行了定性鉴别，采用高效液相色谱法测定了制剂中连翘所含的特征性成分连翘苷的含量，更具专属性。同时对抗病毒滴丸进行了外观性状及其它有关滴丸剂的常规检查，结果表明，由本工艺制得的抗病毒滴丸，外观性状好、崩解度较好、丸重差异小，符合滴丸剂的质量标准。初步稳定生试验表明各项指标均符合规定。生物学评价表明，抗病毒滴丸相比抗病毒胶囊在体外更少的浓度下对病毒的抑制作用明显强于抗病毒胶囊，在体内更少的剂量下可更有效抑制病毒性肺炎，能明显抑制体温升高，具有明显的解热作用、镇痛作用和抗炎作用。综上，与抗病毒胶囊比较，抗病毒滴丸用量小，起效快，作用持续时间长，而未见明显毒副作用，长期连续给药安全可靠。抗病毒滴丸的研制成功，为将大复方中药研制成滴丸剂提供了崭新思路。更多还原

【Abstract】 The anti-viral capsule is composed by the Radix isatidis, gypsum, Radix Rehmanniae, Pogostemon cablin, Fructus Forsythiae, Rhizoma Phragmitis, Radix Curcumae, Acorus tatarinowii Scllott and Anemarrhena asphodeloides Bge, admitted in departmental standard. Its clinical applications have proved the great beneficial effect in the treatment of patients with viral diseases such as the flu, cold due to wind-heat, upper respiratory tract infection. But the anti-viral capsule also has exhibited some disadvantages that the administration dosage is big and the effects is slow, so based on the pharmacology experiment foundation, we purifies the crude extract of anti-viral capsule, reduce the administration dosage, made Drop Pills into a better bioavialability and quicker onset of action. The present paper studies deeply its preparation, quality standard, biological evaluation and preliminary stability. Several studies are included in the thesis:At first according to the physicochemical properties and pharmacological action of the active ingredients of every kind of chinese herbal medicine in Prescriptions, a rational process route has been determined. the volatile oil extraction processes of Pogostemon cablin、Radix Curcumae、Acorus tatarinowii Scllott was established with orthogonal test and single factor experiments. the ethanol extracting technology of Fructus Forsythiae、Anemarrhena asphodeloides Bge, and the water extracting and ethanol precipitating technology of the Radix isatidis、gypsum、Radix Rehmanniae、Fructus Forsythiae, have been determined. then crude extract process was established. On the basis of the pharmacological experiment, the Antiviral effective parts was prepared by purifying the crude extract. The process conditions to make preparation of antiviral Dropping Pills were optimized in terms of spherical degree by studying single factor and orthogonal design test. The the results showed that the drug effect of effective parts purified with 90% ethanol, is superior to the capsule dosage form. The optimized process was as follow: the matrix contained PEG4000: PEG6000(1:1); the refrigerant was methyl-silicon oil; the ratio of limonene to matrix was 1:3 and the temperature of limonene was 80℃; the intemal and extemsl diameter of burette was 2.0mm and 2.4mm, respectively; the burette was 4cm above the surface of refrigerant; drug was dropped into refrigerant of 5℃at 30 drops per minute. In the studie of the antiviral drop pills quality evaluation, a thin layer chromatography method for qualitative distinguishing Radix isatidis、Anemarrhena asphodeloides Bge、Fructus Forsythiae and Pogostemon cablin in prescription medicine were developed, and the contents of forsythin in Fructus Forsythia was determined by HPLC, the Method has good specificity. At the same time, other regular check related to drop pill have been done, the result indicated that Antiviral Droping pills made in this process has good appearance and disintegrate rate, with low weight coefficient of variation, this process is suitable for quality control. The bioevaluation indicate that, Compared with the anti-viral capsule, the anti-viral drop pill has strongly inhibitory action in vitro behind less densities to virus’s, under in vivo less dosage, it may has the more effective suppress virus pneumonia, be able obviously to reduce body temperature, has obvious antithermic action, the analgesia function and the anti-inflammation function. Anti-viral drop pill has less dotage, plays the effect quickly, has longterm of effect time, but has not obvious poisonous side effect, continuously, gives the medicine safely to be reliable for a long time.The investigation of the anti-viral drop pill will provide a novel idea for developing traditional Chinese medicine (TCM) compound by using the proposed dosage form.更多还原