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题名:

 经典名方买朱尼努加的物质基准研究    

作者:

 李秀宇    

学号:

 20182115001    

语种:

 chi    

学科代码:

 1055    

学科:

 药学(专硕)    

学生类型:

 硕士    

学位类型:

 专业学位    

学位年度:

 2022    

学校:

 石河子大学    

院系:

 药学院    

研究方向:

 药物制备及质量控制    

导师姓名:

 马芹    

导师单位:

 新疆华世丹药物研究有限责任公司    

完成日期:

 2022-05-21    

答辩日期:

 2022-05-21    

外文题名:

 Study on the Substance Benchmark of the Classical Prescription "Maizhuninujia"    

关键词:

 经典名方 ; 蜜膏剂 ; 物质基准 ; 维药 ; 炮制     

外文关键词:

 Classical prescription ; Refining honey ; Substance benchmark ; Uighur medicine ; Processing     

摘要:

目的:买朱尼努加出自 1368 年用波斯文编写的维吾尔药专著《依合提亚拉提·拜地依》(拜地依药

书),该方由余甘子、西青果、薰衣草、菟丝草及水龙骨组成,主要用于郁证,如失眠、抑郁症、痴

呆等精神障碍性疾病。通过对所收集到的药材或饮片进行质量评价,筛选出合格的批次;然后根据

维药古籍描述对有炮制要求的药材进行炮制工艺研究,并验证工艺确认工艺参数;在选用传统粉碎

与过筛工具对合格批次的药材或饮片前处理成中间体粉末;最后复现维药传统炼蜜过程,将中间体

粉末与炼蜜混合制备物质基准,为维药经典名方买朱尼努加物质基准的研究提供科学依据。

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,对买朱尼努加组方药材进行性状鉴别、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评价,筛选出合格与最优的药材批次和产地;(2)文献调研总

结出余甘子用牛奶浸渍、西青果用巴旦仁油炒制的过程,分别以没食子酸、总鞣质含量为考察指标,

设计单因素实验优选最佳炮制条件,经三批工艺验证稳定后采用 MTT 法,比较余甘子和西青果在炮

制前后对 293T 肾细胞的 IC 50 值,明确炮制作用;(3)从维药传统粉碎工具石磨、铁船、铜臼与过

筛工具箩、丝绸筛中筛选最接近维药传统用的粉碎与过筛工具;采用单因素试验确认每味药材按处

方量粉碎所需的粉碎时间,判定粉碎难易顺序;然后根据单因素结果设计正交试验,以出粉率、均

一性为考察指标对组方药材与饮片进行粉碎、过筛、混合制得中间体药粉;(4)参考维药炮制规范

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,分别考察炼蜜容器、炼蜜

温度、是否加盖等因素获得最佳工艺,经三批验证后确认炼蜜条件;(5)设计单因素试验将中间体

粉末与炼蜜混合制备物质基准,以 5-羟甲基糠醛、相对密度为指标,依次考察混合方式(药粉加入

炼蜜/炼蜜加入药粉)与搅拌速度(慢速和快速)、药粉与炼蜜的质量比及混合时间等因素,验证工

艺条件后制备 15 批买朱尼努加物质基准。

结果:(1)药材质量检查:组方五味药材共收集到 34 批次,经质量检查 32 批合格,有 2 批薰衣草

的酸不溶性灰分检查项不符合要求。(2)维药特色药材炮制研究:奶制余甘子最佳炮制工艺,以成

品牛奶为炮制辅料,牛奶的用量为药材质量的 20 倍,45℃水浴浸泡 12 h,淋水洗净,干燥即得,炮

制产率约 50%,炮制品中没食子酸含量不到生品的一半;油炒西青果最佳炮制工艺,取药材质量 0.6

倍的巴旦仁油,油温控制在 100~120℃,翻炒 30min,取出晾凉,干燥即得,炮制产率>100%;细

胞毒性试验,余甘子生品 IC 50 值 2.1 mg/mL,余甘子炮制品 IC 50 值>20.6 mg/mL,西青果生品 IC 50

值 1.9 mg/mL,西青果炮制品 IC 50 值>20.7 mg/mL,炮制品细胞毒性较生品降低至少 10 倍。(3)中

间体制备:以铁船为粉碎工具,过筛率最高,药粉均一;用丝绸过筛,丝绸筛药粉细度与蜜膏剂中

药粉细度的要求相当;五味药材粉碎难易顺序为水龙骨/菟丝草→薰衣草→余甘子/西青果;取 1/8 处

方量的药材,一次性投料,粉碎 20 min 即为中间体制备工艺,在中间体药粉中可清晰鉴别出没食子

酸、迷迭香酸、咖啡酸、金丝桃苷及 β-谷甾醇等活性成分。(4)炼蜜研究:最佳炼蜜工艺为广口陶

瓷容器,80℃水浴加热,用木铲连续除去 3 次泡沫,炼蜜较生蜜颜色加深,5-羟甲基糠醛含量符合

标准(<40 μg/g),相对密度约 1.34。(5)买朱尼努加物质基准研究:最佳制备工艺,药粉与炼蜜质

量比为 1:5,炼蜜趁热(70℃)加入到药粉中,快速搅拌 30 min,冷却至室温即得蜜膏。

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、炼蜜工艺及物质基准制备工艺稳定,为买朱尼努加物质基准研究提供基础。

﹀
外摘要要:

Object: “Maizhuninujia” from 1368 written in Persian Uighur medicine aboriginal “Ikhtiarati· Baidiya”

also known as “Medicine Book of Baidiya”, the prescription by Phyllanthus emblica, Chebulae fructus

immaturus, Lavandulae herba, Cuscutae herba and Polypodii rhizoma, mainly used for depression, such as

insomnia, depression, dementia and other mental disorders. Through the quality evaluation of the collected

medicinal materials or decoction pieces, the qualified batches were screened. Then, the processing

technology of medicinal materials with processing requirements was studied according to the description of

ancient Uygur medicine books, and the process parameters were verified. Traditional smashing and sieving

tools were used to process qualified batches of medicinal materials into intermediate powder; reproducing

the traditional honey refining process of Uygur medicine, mixing the intermediate powder with the honey

to prepare the honey ointment, which providing scientific basis for the study of the substance benchmark of

the classic Uygur medicine prescription of “Maizhuninujia”.

Methods: (1) According to the 2020 edition of “Chinese Pharmacopoeia” general principles and

“Processing specification of Uyghur medicinal slices in Xinjiang Uygur Autonomous Region” and the

existing standards issued by the Ministry of Uyghur Medicine, the quality inspection of all batches of

medicinal materials collected in “Maizhuninujia” prescription was carried out, including identification,

impurity, moisture, total ash, acid insoluble ash, extract, content determination and other inspection items.

Compare with the existing standards to determine whether the medicinal materials were qualified, screen

qualified and optimal materials batch and origins. (2) According to the literature research, the process of

soaking Phyllanthus emblica with milk and frying Chebulae fructus immaturus with amygdali dulcis oil

was summarized. Taking gallic acid and total tannin content as indexes, the single factor experiment was

designed to optimize the optimum process conditions. After three batches of process verification, the MTT

method was used to carry out 293 T renal cell toxicity test, and the IC 50 values of Phyllanthus emblica and

Chebulae fructus immaturus before and after processing were compared, and the processing conclusions

were obtained. (3) Screen grinding tools stone mill, iron boat and copper mortar, sieve tools bamboo basket

and silk sieve from ancient Uygur medicine books; single factor test was used to confirm the crushing time

of each herb according to the prescription amount, and the order of difficulty was determined. Then, the

orthogonal test was designed according to the results of single factor, and the intermediate powder was

prepared by crushing, screening and mixing the medicinal materials and decoction pieces with the powder

yield and homogeneity as the indexes. (4) Referring to the written description of honey refining in Uygur

medicine processing specifications, taking the yield, relative density and 5-hydroxymethylfurfural content

as indexes, the optimum process was obtained by investigating the container, temperature and whether to

cover it, and the refined honey conditions were confirmed after three batches of verification; (5) A single

factor experiment was designed to prepare the substance benchmark by mixing powder with refined honey.

With 5-hydroxymethylfurfural and relative density as indexes, the factors such as mixing method

(medicinal powder added to refined honey or refined honey added to powder), stirring speed (slow and fast),

mass ratio of powder to honey and mixing time were investigated in turn. After verification of the process

conditions, 15 batches of substance benchmark for “Maizhuninujia” were prepared.

Results: (1) Quality inspection of medicinal materials: a total of 34 batches of five medicinal materials

were collected, 32 batches were qualified through quality inspection, and the acid insoluble ash of 2

batches of Lavandulae herba did not meet the requirements. (2) Study on the processing of Uygur medicine

characteristic medicinal materials: the best processing technology of milk preparation of Phyllanthus

emblica is as follows: the finished milk is used as the processing auxiliary material, the amount of milk is

20 times of the quality of medicinal materials, soaking in water at 45 °C for 12 h, washing with water,

drying immediately, the average processing yield is about 50%, and the gallic acid content in the processed

products is less than half of the raw products ; the optimal processing technology of fried broccoli was to

extract amygdali dulcis oil 0.6 times the weight of medicinal materials, and the oil temperature was

controlled at 100-120℃, stir frying 30 min, take out cool, dry, the processing yield > 100%; the

cytotoxicity test showed that the IC 50 value of Phyllanthus emblica was 2.1 mg / mL, the IC 50 value of

Phyllanthus emblica processed products was > 20.6 mg/mL, the IC 50 value of Chebulae fructus immaturus

raw products was 1.9 mg/mL, and the IC 50 value of Chebulae fructus immaturus processed products was >

20.7 mg/mL. The cytotoxicity of processed products was at least 10 times lower than that of raw products.

(3) Pretreatment of medicinal materials to prepare intermediates: iron boat as a crushing tool, the highest

powder yield, uniform powder; screened with silk, the fineness of silk powder is equivalent to that of honey

paste. The order of comminution difficulty is Phyllanthus emblica / Chebulae fructus immaturus -

Lavandulae herba - Polypodii rhizoma / Cuscutae herba; taking 1/8 prescription amounts of medicinal

materials, all of them were fed once and crushed for 20 min as the intermediate preparation process. Gallic

acid, rosmarinic acid, caffeic acid, hyperoside and β-sitosterol were clearly identified in the intermediate. (4)

Study on honey refining: the best honey refining process is that the ceramic container with the largest

capacity is heated in 80 °C water bath, and the foam is removed by wood shovel for three consecutive times.

The color of refined honey is deeper than that of honey, and the content of 5-hydroxymethylfurfural meets

the standard (<40 μg/g), and the relative density was about 1.34. (5) Study on the Substance Benchmark of

“Maizhuninujia”: the optimum preparation process is as follows: the mass ratio of powder to refined honey

is 1:5, the refined honey is added to the powder in the heat (70℃), quickly stirred for 30 min, and cooled to

room temperature.

Conclusion: The qualified rate of “Maizhuninujia” prescription is high; the toxicity of Phyllanthus emblica

and Chebulae fructus immaturus was significantly reduced after processing, and the processing technology,

intermediate preparation technology, honey refining technology and substance benchmark preparation

technology were stable, which provides the basis for the reference study of “Maizhuninujia”.

﹀
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开放日期:

 2042-08-31    

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