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中文题名:

 古代经典名方买朱尼努加制剂工艺及质量标准研究    

姓名:

 王楠    

学号:

 20202115017    

保密级别:

 内部1年后开放    

论文语种:

 chi    

学科代码:

 105500    

学科名称:

 医学 - 药学(可授医学、理学学位) - 药学    

学生类型:

 硕士    

学位:

 药学硕士    

学位类型:

 专业学位    

学位年度:

 2023    

学校:

 石河子大学    

院系:

 药学院    

专业:

 药学(专业学位)    

研究方向:

 药物制备及质量控制    

第一导师姓名:

 马芹    

第一导师单位:

 新疆华世丹药物研究有限责任公司    

第二导师姓名:

 陈伟    

完成日期:

 2023-05-10    

答辩日期:

 2023-05-14    

外文题名:

 Study on the technology and quality standard of "Maizhuninujia" preparation of ancient famous prescription    

中文关键词:

 经典名方 ; 蜜膏剂 ; 制剂工艺 ; 维药 ; 质量标准     

外文关键词:

 Classic famous formula ; Honey paste ; Preparation technology ; Uyghur medicine ; Quality standard     

中文摘要:

目的:买朱尼努加为我国维药经典名方遴选目录入选处方,该方出自明代晚期经典民族药物古籍《拜地依药书》,处方由西青果、余甘子、菟丝草、薰衣草及水龙骨等组成,具有清除机体异常脾液质,通阻益脑的作用,用于治疗异常脾液质引起的神经衰弱,健忘症和抑郁证(麻力胡利亚),具有明显特色与优势。本课题通过对所收集到的药材或饮片进行质量评价,筛选出合格批次;然后根据由维药古籍得来的两味药材炮制工艺建立10批次的质量研究;根据买朱尼努加处方中各药味粉碎特性及混合特性总结出中间体粉末工艺,根据传统维医炼蜜过程复现炼蜜工艺,设计单因素实验及正交试验将中间体粉末与炼蜜混合得到制剂工艺,开展买朱尼努加对慢性不可预知温和应激模型药效研究,为维药经典名方买朱尼努加临床上市提供科学依据。

方法:(1)依据2020年版《中国药典》四部通则与《新疆维吾尔自治区中药维吾尔药饮片炮制规范》及现有维药部颁标准,对买朱尼努加组方中收集到的所有批次药材进行鉴别、杂质、水分、总灰分、酸不溶性灰分、浸出物、含量测定等检查项进行质量检查,对照标准判定药材是否合格;(2)对余甘子西青果炮制工艺进行优化,并进行10批次质量研究,对药材性状、水分、总灰分、酸不溶性灰分、浸出物、含量测定等进行测定,同时对余甘子炮制用辅料牛奶进行10批次质量检查;(3)实验先进行单独粉碎确定买朱尼努加处方中各药味粉碎特性,后进行部分粉碎,全方粉碎,确定出最佳粉碎工艺,制定其药材前处理方法,后利用高效混合机比较不同混合时间下中间体粉末中没食子酸、金丝桃苷及迷迭香酸含量的RSD值,选择出最佳混合工艺。(4)参考维药传统工艺中关于炼蜜的文字描述,以产率、相对密度、5-羟甲基糠醛含量为指标,分别考察炼蜜温度、炼蜜时间等因素获得最佳工艺,经三批验证后确认炼蜜工艺;(5)设计单因素及正交实验进行制剂工艺研究,以没食子酸、5-羟甲基糠醛、金丝桃苷含量、相对密度及均一性为指标,依次考察A、B、C、D等因素,并进行验证确定最佳工艺。(6)开展买朱尼努加对慢性不可预知温和应激小鼠模型药效学研究,进行体重监测,行为学考察,细胞因子及HE染色测定及分析,初步建立药效评价。

结果:(1)药材质量检查:组方五味药材共收集到64批次,其中收集余甘子药材16批、西青果16批、菟丝草10批、水龙骨9批,薰衣草药材13批,经质量检查61批合格,余甘子1批次药材含量测定不符合要求,薰衣草有2批次酸不溶性灰分检查项不符合要求。(2)对实验室余甘子炮制工艺优化改变料液比,建立10批次炮制品质量检查研究并讨论,对炮制用辅料牛奶进行10批次质量检查,均合格;(3)根据买朱尼努加处方中各药味粉碎特性总结出粉碎工艺,制定其药材前处理方法,根据出粉率综合考虑选择全方粉碎;后比较不同混合时间中间体粉末中没食子酸、金丝桃苷及迷迭香酸含量的RSD值,选择使用高效混合机混合45 min为优,得到中间体粉末制备工艺;(4)炼蜜研究:最佳炼蜜工艺80℃加热,炼蜜时间30 min,炼蜜较生蜜颜色加深,5-羟甲基糠醛含量符合标准(<40 μg/g)。(5)买朱尼努加制剂工艺研究:最佳工艺为A 100,B 40,C 0.25,D 1:5冷却至室温即得。(6)药效学结果:买朱尼努加中、高剂量组对慢性不可预知温和应激小鼠模型具有一定抗抑郁治疗效果,可改善小鼠行为,其抗抑郁作用与上调单胺类神经递质 5-HT、DA和BDNF的含量有关。

结论:买朱尼努加组方药材合格率高;余甘子与西青果经炮制后毒性明显减弱,炮制工艺、中间体制备工艺、炼蜜工艺及制剂工艺稳定;买朱尼努加具有抗抑郁作用;可为买朱尼努加后续标准提供基础。

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外文摘要:

Object: Maizhuninujia as the selection list of Chinese classic prescription of uyghur medicine. This prescription comes from the classic ancient book of national medicine of the late Ming Dynasty, Baidiyi Medicinal Book. The prescription consists of Phyllanthus emblica , Terminalia chebula Retz, Cuscuta chinensis, Lavandula angustifolia Mill, Rhizoma Polypodiodis Nipponicae, which has the role of clearing abnormal splenic fluid quality, blocking and invigorating brain, and is used to treat neurasthenia caused by abnormal splenic fluid quality. The syndrome of amnesia and depression (Malihuria) has obvious characteristics and advantages. The subject through the quality evaluation of collected medicinal materials or decoction pieces, screened out qualified batches; Then, according to the processing technology of two kinds of medicinal materials obtained from ancient books of uyghur medicine, the quality study of 10 batches was established. The intermediate powder process was summarized according to the smashing characteristics and mixing characteristics of each medicine flavor in Maizhuninujia prescription, and the honey refining process was reperformed according to the traditional honey refining process of TCM. The single factor experiment and orthogonal experiment were designed to mix the intermediate powder and honey to obtain the preparation process, To study the effect of Maizhuninujia on chronic unpredictable mild stress mode, lwhich provided scientific basis for the classic famous prescription of Maizhuninujia prescription to buy the clinical market.

Method: (1) According to the four General rules of the 2020 edition of Chinese Pharmacopoeia, the Processing Standards of Xinjiang Uygur Autonomous Region for Chinese Herbal Medicine Decoction Pieces and the existing standards of the Department of Herbal Medicine, quality inspection was conducted on the identification, impurities, moisture, total ash, acid insoluble ash, extract, content determination and other inspection items of all batches of medicinal materials collected from Maizhuninujia a prescriptions. Check the standard to determine whether the medicine is qualified; (2) The processing technology of P. embalm was optimized, and the quality of 10 batches of P. embalm was studied, and the characters, moisture, total ash, acid insoluble ash, extract and content of the medicinal materials were determined. At the same time, the quality of 10 batches of auxiliary milk used for processing P. embalm was checked. (3) In the experiment, the grinding characteristics of each flavor in Maizhuninujia prescription were determined by individual crushing, followed by partial crushing and whole crushing to determine the optimal grinding process and formulate the pretreatment method of the medicinal materials. After that, the RSDS of the contents of gallic acid, hypericin and rosmarinic acid in the intermediate powder under different mixing times were compared by an efficient mixer to select the optimal mixing process. (4) According to the text description of honey refining in traditional process of uyghur medicine, the yield, relative density and 5-hydroxymethylfurfural content were used as indicators to investigate the honey refining temperature, honey refining time and other factors to obtain the best process, and the honey refining process was confirmed after three batches of verification; (5) Single factor and orthogonal experiments were designed to study the preparation technology. The content, relative density and uniformity of gallic acid, 5-hydroxymethylfurfural and hypericin were taken as indexes, followed by A, B, C, D and other factors, and the optimal process was verified. (6) To conduct pharmacodynamic study of Maizhuninujia on chronic unpredictable mild stress mice model, conduct weight monitoring, behavioral investigation, cytokine and HE staining determination and analysis, and preliminarily establish efficacy evaluation.

Results: (1) Quality inspection of medicinal materials: A total of 64 batches of five medicinal materials of the formulation were collected, including 16 batches of Radix embalmiae, 16 batches of Xanthophylla, 10 batches of tiger herb, 9 batches of aqua keel, and 13 batches of lavender medicinal materials. Sixty-one batches were qualified through quality inspection, the content determination of Radix embalmiae in one batch did not meet the requirements, and the inspection items of acid insoluble ash in two batches of lavender did not meet the requirements. (2) Optimize the processing technology of Camellia japonicum in the laboratory to change the ratio of material to liquid, establish and discuss the quality inspection of 10 batches of gun products, and carry out the quality inspection of 10 batches of auxiliary milk for processing, all qualified; (3) According to the grinding characteristics of each flavor in Maizhuninujia prescription, the grinding process was summarized, the pretreatment method of the medicinal materials was formulated, and the whole method of grinding was selected according to the powder yield. After comparing the RSDS of gallic acid, hypericin and rosmarinic acid in the intermediate powder with different mixing time, the optimal mixing time was 45 minutes in the high efficiency mixer. The preparation process of the intermediate powder was obtained. (4) Honey refining research: The best honey refining process was heated at 80℃ for 30 minutes. The color of honey was darker than that of raw honey. The content of 5-hydroxymethylfurfural met the standard (< 40 μg/g). (5) Study on the process of Maizhuninujia preparation: the best process is A 100, B 40, C 0.25, D 1:5 cooling to room temperature. (6) Pharmacodynamic results: Maizhuninujia medium and high dose groups have certain antidepressant treatment effect on the chronic unpredictable mild stress mouse model, and can improve the behavior of mice. The antidepressant effect is related to the upregulation of monoamine neurotransmitters 5-HT, DA and neurotrophic factors.

Conclusion: The qualified rate of Maizhuninujia formula is high. After processing, the toxicity of Phyllanthus emblica Land Terminalia chebula Retz was significantly reduced, and the processing technology, intermediate preparation technology, honey refining technology and preparation technology were stable, Maizhuninujia has antidepressant effects; Can provide the basis for the purchase of subsequent Maizhuninujia standards.

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中图分类号:

 R94    

开放日期:

 2024-06-06    

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