女贞子炮制工艺及质量标准的研究
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摘要
女贞子系木樨科植物(Ligustum lucidum Ait)女贞的干燥成熟果实,收载于《中国药典》2005版一部。味甘、苦,性凉,具有滋补肝肾,明目乌发的功效。用于治疗眩晕耳鸣,腰膝酸软,目暗不明,须发早白。
本课题是国家重大科技专项“创新药物和中药现代化”研究的一部分,在原国家中医药管理局青年基金项目“女贞子酒制工艺实验研究”基础上进行的深入研究。具体内容如下:
采用溶剂和色谱方法对女贞子果实的80%乙醇提取物进行了化学成分的分离和纯化研究,从中分离得到特征性水溶性成分—特女贞苷约900mg,其中纯度98%以上的约100mg,依据化学和波谱分析方法进行了结构鉴定。
女贞子临床应用多以炮制品入药,且以酒制法为多。从1963年至2005年版《中国药典》均记载女贞子为加黄酒拌匀炖法或蒸法。关于女贞子的酒制,全国各地在加酒量和时间上,差异很大。为此,采用正交实验方法,以齐墩果酸为含测指标,加酒量(A)、蒸制时间(B)和烘干温度(C)为考察因素,对女贞子的炮制工艺进行优选。结果显示:A因素和C因素有统计意义,B因素无统计意义。影响酒制关键因素是加酒量,其次是烘干温度,结合外观色泽以及各地区传统炮制经验,确立了其炮制工艺:黄酒加入量为20%,蒸制时间为4h,烘干温度为70℃。将实验室工艺中试放大,进行质量标准研究,建立饮片质量标准,为规范饮片炮制和有效市场监控提供科学的依据。
建立了女贞子药材及中试饮片中齐墩果酸和熊果酸的HPLC测定方法,方法学考察表明:方法稳定可靠,重现性好,齐墩果酸、熊果酸的回收率分别为98.64%和98.25%,RSD分别为0.46%和1.05%。含量测定表明:14个产地女贞子药材齐墩果酸含量范围在0.719%～1.579%,熊果酸含量范围在0.176%～0.519%,齐墩果酸和熊果酸总量范围在0.907%～2.086%。中试饮片齐墩果酸含量范围在0.914%～1.640%,熊果酸含量范围在0.285%～0.484%,齐墩果酸和熊果酸总量范围在1.199%～2.114%。齐墩果酸、熊果酸无论在化学结构、色谱鉴别、分离条件和药理作用上都比较相近。建议药典在女贞子药材标准项下增加齐墩果酸和熊果酸总含量,规定总含量应不得少于1.0%,饮片含量应不得少于1.1%。
同时以特征性有效成分特女贞苷为指标,建立女贞子药材及中试饮片的HPLC测定方法,并进行了方法学考察,特女贞苷的回收率为101.97%,RSD为1.37%。12个产地女贞子药材中特女贞苷的含量范围在0.241%～4.451%之间,地区差异较大,这可能与样品产地、采集时间、样品初加工、样品储藏时间以及市售药材产地混乱等因素有关。中试饮片中特女贞苷的含量范围在0.260%～0.775%,与炮制药材相比,特女贞苷的含量有所下降,这可能与炮制前水洗、蒸制时间过长、烘干温度以及特女贞苷(环烯醚萜结构)本身性质等因素有关,建议(1)女贞子酒制,净选后,黄酒伴匀,低温干燥或直接
Fructus Ligustri lucidi is from the dried fruit of Ligustrum lucidum Ait.,family Oleaceae, which is accepted in 2005 edition of Chinese Pharmacopoeia, sweet or bitter in flavor, cold in nature, It has the effect of nourishing liver and invigorating the kidney , and promoting the eyesight and blackening the hair.Use for dizziness and tinnitus,soreness and weakness of waist and kness, manifestations of blurred vision and weakness of eyesight, premature whitening of hair,This subject coming from the item of innovative medicine and TCM modernization of national important science And technology, which is much deeper research of Fructus Ligustri lucidi on the base of wine processing technique experiment of young fund of administration of traditional Chinese medicine. Specific content as follow.IN my phytochemical research of the fruit of Fructus Ligustri lucidi growing in HeNan .characteristic water solubility ingredient — specnuezhenide(about 900mg) is extracted and separated from extractive of 80% ethanol by using different isolating technique, above 98 percent of purity in which is about 100mg,95 percent of purity about 800mg, On the basis of chemical properties and spectroscopic analysis, the compound were identified.Fructus Ligustri lucidi was used in the from of its processed product in the clinic, wine processing technique is also mainly method, the procedure of braizing or steaming with yellow wine are known in the china pharmacopoeia (from 1963 edition to 2005 edition).At present, wine processing about Fructus Ligustri Lucidi countrywide are much diffenence in the quantity of wine and processing time. For this reasion, using orthogonal design,I optimized theprocessing procedure by the index of Oleanolic acid and the factors of adding wine quantity(A), steaming time(B) and torrefying temperature (C). The results demonstrate: A factor and C factor ,having statistical significance;B factor , no notable statistical significance. Principal factor of influencing quality of Fructus Ligustri lucidi processing with wine is adding wine quantity, the lesser is torrefying temperature, steaming time is unessential. Allowing for external, colour and traditional processing experiences of individual areas, definitive processing technique is 20percent yellow wine,4hour steaming, 70 °C torrefaction. The techniques of laboratory are validated by medium-scale production,quality specification are done.The.chosen techniques will provide scientific foundation for processing products standard and market monitoring in force.
The developed HPLC method were used quantitative analysis of Fructus Ligustri lucidi and its processing products by the index of Oleanolic acid and Ursolic acid. The recovery of Oleanolic acid is 98.64%,RSD is 0.46%;The recovery of Ursolic acid is 98. 25%, RSD is 1. 05%. Assayings of 14 habits show: contents range of Oleanolic acid are 0.719%'— 1.579%, Ursolic acid contents range of 14 habits are 0. 176%~0. 519%, total amount range of Oleanolic acid and Ursolic acid are 0. 907%~2. 086%;Assayings of Processing products show: contents range of Oleanolic acid are 0. 914%~1.640%, contents range of Ursolic acid are 0. 285%~ 0. 484%, total amount range of Oleanolic acid and Ursolic acid are 1. 199%~2. 114%. Regardless of chemical const i tut ion> colour spectrum identification -. separating condition and pharmacological action, Oleanolic acid and Ursolic acid are rather similar. Advising adding the total amount of Oleanolic acid and Ursolic acid in Pharmacopoeia, The total amount of Oleanolic acid and Ursolic acid in Medicinal substances can not less 1.0%, The total amount of Oleanolic acid and Ursolic acid in processing product can not less 1.1% .The developed HPLC method were used quantitative analysis and a series of technology investigation of Fructus Ligustri lucidi and its processing products by the index of Specnuezhenide. The recovery of Specnuezhenide islOl. 97%,RSD is 1.37%. Specnuezhenide content range of 13 habits are 0. 241%-— 4. 451% .region difference is comparatively large, possible reasons relate sample habit, collecting time ■. sample pretreating > sample reserving and marketing herbs confusion. Specnuezhenide content range of processing products are 0. 260%~ 0. 775%, contrasting processing herbs , The contents of Specnuezhenide degrade, possible reasons relate water washing pre-processing , steaming time long, torrefying temperature and Specnuezhenide quality. Advising: (1) Wine processing of Fructus Ligustri lucidi, met a-clean ing select ion, yellow wine mixing thoroughly, cryodrying or direct drying. (2) Adding the content of Specnuezhenide in Pharmacopoeia, according to value of Specnuezhenide in the herb of HeNan,the content can not less 0.40%;The content in processing product cannot less 0. 25%.The developed spectrophotometric method were used quantitative analysis and stable investigation of semi-works production processing products by the index of polysaccharose and mannitol. Assayings show:The content of processing drugs circa are not changing.In addition, carrying out determination of TLC> Moisture , Ash content >Indissolvable acid ash content ,alcohol-soluble extractive^
heavy metaK farming leftover. Advising : Improving Oleanolic acid TLC of Fructus Ligustri lucidi in pharmacopoeia, Establishing TLC of Specnuezhenide, (1) Medicinal substances:The total content of Oleanolic acid and Ursolic acid are not less than 1.00%, moisture content not less than 8.0%, alcohol-soluble extractive not less than 22. 00%(2) Processing products: The total content of Oleanolic acid and Ursolic acid not less than 1. 00%, moisture content less than 5. 5% , ash content less than 5. 5%, indissolvable acid ash content less than 0. 75%, alcohol-soluble extractive not less than 20.00%.The quality standard (protocol) and draft directions of the quality standard are Instituted.The stability studies of processing products in six months showed they were stable in natural condition.To bring new idea,1. On the base of traditional processing techniques and producing practice, the key technical parameters (adding winequantity, steaming time and torrefying temperature)of Fructus Ligustri lucidi are established , providing scientific groundwork for large scale controling production.2. Characteristic water solubility ingredient —specnuezhenide(about 900mg) is extracted and separated by using different isolating technique, above 98 percent of purity in which is about lOOmg, 95 percent of purity about 800mg. (3)The developed methods of content determinatiomand a seris of technology investigation are for Oleanolic acid, Ursolic acid, Specnuezhenide, Polysaccharose and Mannitol 4.Revising and supplementing many contents of Fructus Ligustri Lucidi item in the china pharmacopoeia(2005 edition). (1). Revising the Oleanolic acid TLC condition of Fructus Ligustri lucidi. (2).Adding the specnuezhenide TLC condition of Fructus Ligustri Lucidi. (3). Revising Oleanolic acid determination of thin layer scaning.(4).Supplementing specnuezhenide determination of HPLC.(5).Adding detection items of moisture content,ash content, indissolvable acid ash content. (6). Adding detection items of alcohol-soluble extractive.5.The quality standard(protocol) and draft directions of the quality standard are established.
本课题是国家重大科技专项“创新药物和中药现代化”研究的一部分,在原国家中医药管理局青年基金项目“女贞子酒制工艺实验研究”基础上进行的深入研究。具体内容如下:
采用溶剂和色谱方法对女贞子果实的80%乙醇提取物进行了化学成分的分离和纯化研究,从中分离得到特征性水溶性成分—特女贞苷约900mg,其中纯度98%以上的约100mg,依据化学和波谱分析方法进行了结构鉴定。
女贞子临床应用多以炮制品入药,且以酒制法为多。从1963年至2005年版《中国药典》均记载女贞子为加黄酒拌匀炖法或蒸法。关于女贞子的酒制,全国各地在加酒量和时间上,差异很大。为此,采用正交实验方法,以齐墩果酸为含测指标,加酒量(A)、蒸制时间(B)和烘干温度(C)为考察因素,对女贞子的炮制工艺进行优选。结果显示:A因素和C因素有统计意义,B因素无统计意义。影响酒制关键因素是加酒量,其次是烘干温度,结合外观色泽以及各地区传统炮制经验,确立了其炮制工艺:黄酒加入量为20%,蒸制时间为4h,烘干温度为70℃。将实验室工艺中试放大,进行质量标准研究,建立饮片质量标准,为规范饮片炮制和有效市场监控提供科学的依据。
建立了女贞子药材及中试饮片中齐墩果酸和熊果酸的HPLC测定方法,方法学考察表明:方法稳定可靠,重现性好,齐墩果酸、熊果酸的回收率分别为98.64%和98.25%,RSD分别为0.46%和1.05%。含量测定表明:14个产地女贞子药材齐墩果酸含量范围在0.719%～1.579%,熊果酸含量范围在0.176%～0.519%,齐墩果酸和熊果酸总量范围在0.907%～2.086%。中试饮片齐墩果酸含量范围在0.914%～1.640%,熊果酸含量范围在0.285%～0.484%,齐墩果酸和熊果酸总量范围在1.199%～2.114%。齐墩果酸、熊果酸无论在化学结构、色谱鉴别、分离条件和药理作用上都比较相近。建议药典在女贞子药材标准项下增加齐墩果酸和熊果酸总含量,规定总含量应不得少于1.0%,饮片含量应不得少于1.1%。
同时以特征性有效成分特女贞苷为指标,建立女贞子药材及中试饮片的HPLC测定方法,并进行了方法学考察,特女贞苷的回收率为101.97%,RSD为1.37%。12个产地女贞子药材中特女贞苷的含量范围在0.241%～4.451%之间,地区差异较大,这可能与样品产地、采集时间、样品初加工、样品储藏时间以及市售药材产地混乱等因素有关。中试饮片中特女贞苷的含量范围在0.260%～0.775%,与炮制药材相比,特女贞苷的含量有所下降,这可能与炮制前水洗、蒸制时间过长、烘干温度以及特女贞苷(环烯醚萜结构)本身性质等因素有关,建议(1)女贞子酒制,净选后,黄酒伴匀,低温干燥或直接
Fructus Ligustri lucidi is from the dried fruit of Ligustrum lucidum Ait.,family Oleaceae, which is accepted in 2005 edition of Chinese Pharmacopoeia, sweet or bitter in flavor, cold in nature, It has the effect of nourishing liver and invigorating the kidney , and promoting the eyesight and blackening the hair.Use for dizziness and tinnitus,soreness and weakness of waist and kness, manifestations of blurred vision and weakness of eyesight, premature whitening of hair,This subject coming from the item of innovative medicine and TCM modernization of national important science And technology, which is much deeper research of Fructus Ligustri lucidi on the base of wine processing technique experiment of young fund of administration of traditional Chinese medicine. Specific content as follow.IN my phytochemical research of the fruit of Fructus Ligustri lucidi growing in HeNan .characteristic water solubility ingredient — specnuezhenide(about 900mg) is extracted and separated from extractive of 80% ethanol by using different isolating technique, above 98 percent of purity in which is about 100mg,95 percent of purity about 800mg, On the basis of chemical properties and spectroscopic analysis, the compound were identified.Fructus Ligustri lucidi was used in the from of its processed product in the clinic, wine processing technique is also mainly method, the procedure of braizing or steaming with yellow wine are known in the china pharmacopoeia (from 1963 edition to 2005 edition).At present, wine processing about Fructus Ligustri Lucidi countrywide are much diffenence in the quantity of wine and processing time. For this reasion, using orthogonal design,I optimized theprocessing procedure by the index of Oleanolic acid and the factors of adding wine quantity(A), steaming time(B) and torrefying temperature (C). The results demonstrate: A factor and C factor ,having statistical significance;B factor , no notable statistical significance. Principal factor of influencing quality of Fructus Ligustri lucidi processing with wine is adding wine quantity, the lesser is torrefying temperature, steaming time is unessential. Allowing for external, colour and traditional processing experiences of individual areas, definitive processing technique is 20percent yellow wine,4hour steaming, 70 °C torrefaction. The techniques of laboratory are validated by medium-scale production,quality specification are done.The.chosen techniques will provide scientific foundation for processing products standard and market monitoring in force.
The developed HPLC method were used quantitative analysis of Fructus Ligustri lucidi and its processing products by the index of Oleanolic acid and Ursolic acid. The recovery of Oleanolic acid is 98.64%,RSD is 0.46%;The recovery of Ursolic acid is 98. 25%, RSD is 1. 05%. Assayings of 14 habits show: contents range of Oleanolic acid are 0.719%'— 1.579%, Ursolic acid contents range of 14 habits are 0. 176%~0. 519%, total amount range of Oleanolic acid and Ursolic acid are 0. 907%~2. 086%;Assayings of Processing products show: contents range of Oleanolic acid are 0. 914%~1.640%, contents range of Ursolic acid are 0. 285%~ 0. 484%, total amount range of Oleanolic acid and Ursolic acid are 1. 199%~2. 114%. Regardless of chemical const i tut ion> colour spectrum identification -. separating condition and pharmacological action, Oleanolic acid and Ursolic acid are rather similar. Advising adding the total amount of Oleanolic acid and Ursolic acid in Pharmacopoeia, The total amount of Oleanolic acid and Ursolic acid in Medicinal substances can not less 1.0%, The total amount of Oleanolic acid and Ursolic acid in processing product can not less 1.1% .The developed HPLC method were used quantitative analysis and a series of technology investigation of Fructus Ligustri lucidi and its processing products by the index of Specnuezhenide. The recovery of Specnuezhenide islOl. 97%,RSD is 1.37%. Specnuezhenide content range of 13 habits are 0. 241%-— 4. 451% .region difference is comparatively large, possible reasons relate sample habit, collecting time ■. sample pretreating > sample reserving and marketing herbs confusion. Specnuezhenide content range of processing products are 0. 260%~ 0. 775%, contrasting processing herbs , The contents of Specnuezhenide degrade, possible reasons relate water washing pre-processing , steaming time long, torrefying temperature and Specnuezhenide quality. Advising: (1) Wine processing of Fructus Ligustri lucidi, met a-clean ing select ion, yellow wine mixing thoroughly, cryodrying or direct drying. (2) Adding the content of Specnuezhenide in Pharmacopoeia, according to value of Specnuezhenide in the herb of HeNan,the content can not less 0.40%;The content in processing product cannot less 0. 25%.The developed spectrophotometric method were used quantitative analysis and stable investigation of semi-works production processing products by the index of polysaccharose and mannitol. Assayings show:The content of processing drugs circa are not changing.In addition, carrying out determination of TLC> Moisture , Ash content >Indissolvable acid ash content ,alcohol-soluble extractive^
heavy metaK farming leftover. Advising : Improving Oleanolic acid TLC of Fructus Ligustri lucidi in pharmacopoeia, Establishing TLC of Specnuezhenide, (1) Medicinal substances:The total content of Oleanolic acid and Ursolic acid are not less than 1.00%, moisture content not less than 8.0%, alcohol-soluble extractive not less than 22. 00%(2) Processing products: The total content of Oleanolic acid and Ursolic acid not less than 1. 00%, moisture content less than 5. 5% , ash content less than 5. 5%, indissolvable acid ash content less than 0. 75%, alcohol-soluble extractive not less than 20.00%.The quality standard (protocol) and draft directions of the quality standard are Instituted.The stability studies of processing products in six months showed they were stable in natural condition.To bring new idea,1. On the base of traditional processing techniques and producing practice, the key technical parameters (adding winequantity, steaming time and torrefying temperature)of Fructus Ligustri lucidi are established , providing scientific groundwork for large scale controling production.2. Characteristic water solubility ingredient —specnuezhenide(about 900mg) is extracted and separated by using different isolating technique, above 98 percent of purity in which is about lOOmg, 95 percent of purity about 800mg. (3)The developed methods of content determinatiomand a seris of technology investigation are for Oleanolic acid, Ursolic acid, Specnuezhenide, Polysaccharose and Mannitol 4.Revising and supplementing many contents of Fructus Ligustri Lucidi item in the china pharmacopoeia(2005 edition). (1). Revising the Oleanolic acid TLC condition of Fructus Ligustri lucidi. (2).Adding the specnuezhenide TLC condition of Fructus Ligustri Lucidi. (3). Revising Oleanolic acid determination of thin layer scaning.(4).Supplementing specnuezhenide determination of HPLC.(5).Adding detection items of moisture content,ash content, indissolvable acid ash content. (6). Adding detection items of alcohol-soluble extractive.5.The quality standard(protocol) and draft directions of the quality standard are established.
引文
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