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o EUROPEANMEDICINES AGENCY SCIENCE MEDICINES HEALTH 16 September2010 EMA/HMPC/186645/2008 Patient Health Protection Committee on Herbal MedicinalProducts (HMPC) Reflection paper on the level of purification ofextracts to be considered as herbal preparations
被认为是草药加工品的提取物纯化水平的思考
Draft agreed by HMPC drafting group on quality | | | | | | Adoption by HMPC for release for consultation | | End of consultation (deadline for comments) | | Second draft agreed by HMPC drafting group on quality | | | 16 September 2010 |
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Reflection paper on thelevel of purification of extracts to be considered as herbal preparations Table of contents 4.1. Level of refinement...................................................................................... 5 4.2. Presence of concomitant constituents............................................................ 5 4.3. Methods of extraction/refining....................................................................... 5 4.4. Examples of categories of preparation of herbalorigin................................... 5 Examplesconsidered as herbal preparations....................................................... 10 Examplesnot considered as herbal preparations ................................................ 11 Examplesfor borderline cases........................................................................... 11 1. EXECUTIVE SUMMARY 执行摘要 This reflection paper applies to extractsused as active substances in herbal medicinal products (HMPs) both for humanand veterinary use and in traditional herbal medicinal products (THMPs) forhuman use. 这篇思考文章适用于作为活性物质的提取物，这些提取物用于人用和兽用草药药品（HMPs）以及人用传统草药药品(THMPs)。 The purpose of this reflection paper is toconsider aspects related to the different levels of purification of extractsand to provide criteria to distinguish between those extracts that may beconsidered as herbal preparations and those that might be, more correctly,classified as isolated herbal constituent or purified mixtures of herbalconstituents, taking into account that the final decision has to be taken on acase by case evaluation。 这篇思考文章的目的在于考虑不同提取物的纯化水平，并且提供标准来区分那些可能被认为是草药加工品和那些可被划分为独立的草药成分或草药成分纯化混合物。当然最终应如何界定需要根据不同情况具体评估。 The aim is toprovide clarification on which existing guidance documents should be used fordifferent herbal refined extracts in order to assist applicants in identifyingthe most appropriate authorisation/registration procedure. 其目的在于对不同草药提取物应使用何种指南文件提供明确方案，帮助申请者来去识别最为适合的注册程序。 2. INTRODUCTION (Background) 介绍（背景） The Directive 2001/83/EC asamended provides definitions for HMPs, herbal substances and herbalpreparations. The same basic legislation applies to both HMPs and othermedicinal products [1].An additional simplified registration procedure has been established for THMPs. 修订的2001/83/EC法令提供了HMPs、药材和草药加工品的定义。同样，该法令也适用于其他产品。另外为THMPs建立了额外的简易注册程序。 According to these definitions a herbalmedicinal product is any medicinal product, exclusively containing as activeingredients one or more herbal substances or one or more herbal preparations,or one or more such herbal substances in combination with one or more suchherbal preparations. 根据这些定义，所谓草药药品即为一种药品，它专门包含作为活性成分的一种或几种药材、或者一种或几种草药加工品、或者一种或几种药材与一种或几种草药加工品的复合物。 THMPs may contain also vitamins and minerals, provided that theaction of the vitamins or minerals is ancillary to that of the herbal activeingredients. THMPs 也许会包含维他命和矿物质，前提是维他命和矿物质随着草药活性成分发挥其作用。 Many chemical moieties are obtained byextraction and purification from plant material and it has been clarified [2]that products containing isolated chemically defined constituents (irrespectiveof whether they are of natural or synthetic origin) or a mixture thereof arenot HMPs. 在植物提取和纯化过程中会获得很多的化学基团，现在已经澄清这样一个事实，即当产品中包含单独的化学确定成分（不管是否为自然成分还是合成来源）或包含有化学确定成分的混合物都不属于草药药品（HMPs）。 HMPs have anumber of characteristics that differentiate them from medicinal productscontaining isolated chemically defined active substances and therefore specificguidelines have been established, which cover particular aspects that generalguidelines do not address. It should be noted that herbal substances and herbalpreparations are complex mixtures of natural constituents which altogether formthe “active substance”. This includes those constituents that may arise fromnatural transformations. HMPs有许多特征，这些特征不同于那些包含单独化学确定活性物质的药品。因此已建立了针对HMPs的特定指南，这些指南涵盖了一般指南未强调的特殊方面。应注意的是药材和草药加工品作为自然成分混合物共同构成了所谓的“活性物质”。这包含了那些可能经过自然转变的成分。 3. PROBLEM STATEMENT 问题陈述 The definition forherbal preparations covers not only simply processed preparations obtained byone step extraction but also purified and concentrated preparations such asrefined extracts. Extraction with a given solvent leads to typical proportionsof constituents in the extractable matter. Unwanted matter may be removed afterextraction for safety reasons and/or to improve the pharmacological activity ofextracts and also for quality reasons. 草药加工品，其不仅包含通过一步提取获得简单加工品，同时也包含纯化和浓缩物诸如精制提取物。当使用溶剂提取时会使最终萃取物中包含一些典型的成分组成。为安全考虑和（或）提高提取物的药理活性和质量那些不需要的物质会在提取过程中去除。 In the case of standardised and quantified extracts,purification procedures may be applied with the aim of increasing the contentof constituents with known therapeutic activity or active markers. Suchextracts are referred to as “refined” in the European Pharmacopoeia. 对于标准化和量化型提取物，纯化步骤的目的是为了提高已知治疗活性成分或活性标记物的含量。这类提取物在欧洲药典中被称为精制加工品。 In some cases the purification of a herbal extract isso substantial that it is questionable whether the resulting preparation maystill be considered as a highly purified herbal preparation or whether itshould be regarded as an isolated herbal constituent or a mixture of closelyrelated herbal constituents. 在一些情况下提取纯化到了极致，以至于会产生这样的疑问：这类加工品还会被认为是高度纯化的草药加工品么？或者是否应被看做一个独立的草药成分或与之密切相关的成分混合物？ In other circumstances the extract may have beenpreviously fractionated and/or refined and then mixed again to form the finalpreparation。 在其它情况下，提取物也许已经过了分馏和（或）精制，之后混合形成最终加工品。 There is a broad range of possibilities for refiningof extracts, including blending and mixing different fractions. In most casesthe classification is clear and the purification does not change the status ofthe extract as a “herbal preparation” even for substantially refined andconcentrated herbal preparations. 精制提取物有广泛的可能性，包含不同分馏物的混合。在许多情况下，分类是明确的，其纯化往往不会改变提取物作为“草药加工品”这一身份，即便精制和浓缩到极致，它们仍是草药加工品。 However, a grey area remains both for highly refined,concentrated extracts and for extracts consisting predominantly of mixtures ofrelated constituents which do not comply with the general quality guidelines [3] on substances for pharmaceutical use. 然而，一个灰色地带仍存在，既对于高度精制浓缩的提取物，同样也对于主要包含相关成分混合的提取物（相关成分指不符合药用物质一般质量指导原则）。 Therefore a careful evaluation of the borderline isneeded to ensure the correct category is assigned in order to establish theappropriate specifications and regulatory status. 因此，应对临界点进行谨慎的评估以确保分类准确，便于建立合适的质量标准和规范管理。 The purpose of this reflection paper is to considercriteria to discriminate between highly purified extracts which can still beconsidered as herbal preparations and other preparations which should beconsidered as isolated herbal constituents or mixtures of related herbalconstituents. 这篇思考文章的目的在于考虑标准以区分可被认为草药加工品的高纯化提取物和那些应被认为是一个独立的草药成分或相关草药成分混合物的其它加工品。 4. DISCUSSION 讨论 The quality of a medicinal product is independent ofits use and therefore all general principles of quality and quality guidancedocuments also apply to HMPs. 每种药品的质量都独立于其使用目的，因此所有关于质量的一般原则和指南都适用于草药药品。 Due to their complex nature, specific herbalguidelines provide further information on how the quality issues should beaddressed in the case of herbal substances/herbal preparations/HMPs. 由于其复杂的自然属性，一些特定的草药指南提供了针对药材/草药加工品/草药药品应如何强调其质量问题的更多信息。 For single, isolated constituents from herbal origin(e.g. morphine) adherence to the general quality guidelines for chemicallydefined active substances is required. 对于植物来源中的单一独立成分（如吗啡）应遵守化学确定活性物质一般指导原则是必须的。 Active substances in HMPs consist of complex mixturesof phytochemical constituents. For many herbal substances and herbalpreparations, the constituents responsible for the therapeutic activity are notknown. In addition, there are herbal preparations where neither constituentswith known therapeutic activity nor active markers are known. These herbalpreparations are characterised by their production process and theirspecifications. They are described as “other” extracts in the EuropeanPharmacopoeia. 草药药品中的活性物质包含含植物化学成分的复杂混合物。对许多药材和草药加工品，具有治疗效果的活性成分是未知的。另外，一些草药加工品既不知道其治疗活性物质也不知道其活性标记物。这类草药加工品特征在于其生产过程和其质量标准。它们在欧洲药典中被描述为“其它”提取物。 Refining extracts may aim to reduce problematicalconstituents or to increase the content of active constituents (standardisedextracts and quantified extracts with reference to the European Pharmacopoeia).During the refining process the composition of the final preparation may varyto a greater or lesser extent but in general the refined extracts no longerhave the total spectrum of constituents present in the original extract。 精制提取物的目的在于降低问题成分或提高活性成分（标准提取物和具有欧洲药典参考标准的量化提取物）的含量。在精制过程中最终加工品的构成或多或少发生改变，但通常来讲精制提取物不再含有提纯前提取物中总的光谱成分。 The different purification steps lead from “totalextracts”（natural multi-component mixtures) via “refined extracts”（includingmixtures of closely related constituents) finally to “isolated singleconstituents”. Increasing the purification of total extracts converges theactive substances more and more towards isolated chemically defined substances.Sometimes the herbal matrix of natural concomitants is completely removed, eventhough the level of purification achieved is not the same as a single chemicalentity. 不同的纯化步骤使得“总提取物”（自然多组分混合物）通过精制提取（包括密切相关成分混合物）最终成为“独立的单一成分”。不断提高总提取物的纯化水平将使活性成分越来越趋向于独立的化学确定物质。即便纯化水平不同于一个单一的化学实体，有时候自然伴随的草药基质也会完全去除。 Although the final evaluation has to be made on acase by case basis, the following aspects which characterise the differentextracts should be taken into account for the assessment: level of refinement,purification level with regard to the presence of residual concomitants, methodof purification. 尽管最终的评估是基于每个具体的情况，但应考虑到以下在特征化不同提取物时应评估的方面：精制水平，纯化水平（关于残留物），纯化方法。 4.1. Level of refinement 精制水平 DER native and level of refinement are important factors to define thepreparation, but they do not determine per se the classification as a herbalpreparation. Methods used in refining and purification may be more relevant forthis purpose. 自身的药物提取比例和精制水平是定义加工品的重要因素，但它们不是确定其作为草药加工品本身的分类。精制和纯化中使用的方法也许更多会与其目的相关。 It is worth noting that even for some chemicallydefined active ingredients, especially of natural/biological origin, thestandard degree of purity NLT 95% is not applied, wherejustified (e.g. antibiotics). 应值得注意的是即使对于一些化学确定活性物质而言，尤其是自然/生物来源的，不低于95%的纯度标准并不适用，除非有合理的理由（如抗生素）。 Concerning refined extracts, the critical thresholdfor the case by case evaluation is generally considered to be above 70% of active constituent(s). 关于精制提取物，根据每个具体情况评估的临界点通常认为是要高于活性成分的70%。 4.2. Presence of concomitant constituents 附随成分 With HMPs, the whole herbal preparation is consideredto be the “active substance” and all constituents originating from the plantmaterial (concomitant constituents) are considered to be part of the activesubstance and not impurities. However, if the active substance is classified asan isolated chemically defined compound, all other constituents originatingfrom the herbal substance would be considered as impurities. 对于草药药品，其总加工品被认为是“活性物质”，而所有来源于植物体成分（附随成分）被认为是活性物质的一部分并非杂质。然而，如果活性物质被界定为独立的化学确定成分，那么所有附随成分应被认为是杂质。 4.3. Methods of extraction/refining 提取/精制的方法 Chemical modifications of original constituents mayoccur during the extraction process or following refining and it is notinfrequent that artefacts are present in the extract, e.g. as a consequence offermentation, heating, hydrolysis, etc. 在提取过程或之后的精制过程也许会发生原始成分的化学修饰。提取中呈现有人工制品形式的物质不是罕见的，例如由于发酵、加热、水解作用等。 Naturally occurring changes in the originalcomposition of the plant material during the manufacturing process areacceptable, provided that they are consistently controlled. 在生产过程中植物物料的原始成分自然发生变化是可以接受的，前提是它们处于持续控制中。 Several refining processes exist. Appropriatejustifications are needed for the methods employed. 一些精制过程是存在的。对于所采取的方法需要提供合适的理由。 4.4. Examples of categories of preparation of herbalorigin 草药加工品分类举例 In relation to the composition of the preparation of herbal origin,the following different categories can be identified: 关于草药加工品的构成，以下内容可用于识别不同的分类： a) Isolated constituent (e.g. morphine) for which a characteristicimpurity profile may be established and the purity has to be proven within theusual margins of acceptance for chemical substances. 单独的成分（例如吗啡），这类物质的特征杂质分布也许需要建立，而且其纯度应被证实在化学物质通常可接受边缘范围内。 b) Mixtures of purified constituents obtained by specific processingmethods (e.g. precipitation of sennosides as calcium salts). Concomitantconstituents have been removed or are present at insignificant levels. 通过特殊的处理过程得到的纯化成分混合物（例如作为钙盐的番泻苷析出物）。附随成分已被去除或其含量并不显著。 c) Mixtures of chemically defined substances with related chemicalstructures extracted from herbal material. These may be difficult to separate(e.g. alkaloid fraction not containing N- oxides or quaternary alkaloids,saponin fraction containing only monodesmosides saponins). Concomitantconstituents have been removed or are present at insignificant levels. 从草药中提取的具有化学结构的化学确定物质混合物。它们也许很难分离（例如不包含N-氧化物或第四级生物碱的生物碱片段、只包含皂苷的皂苷片段）。附随成分已被去除或其含量并不显著。 d) Chemically defined compounds extracted from herbal material andpartially purified, e.g. 85%, but where the remaining part is represented by concomitantconstituents. 从草药中提取的化学确定成分经部分纯化，例如85%，其余部分为附随成分。 e) Isolated class of constituents (e.g. total alkaloids, total saponinsfraction) maintaining the natural variability for whichidentification of the main constituents in the mixture is possible. 独立的一类成分（例如总生物碱，总皂苷片段），这类成分具有其本身的可变特征，在混合物中对这类成分进行鉴别是可能的。 f) Standardised extracts adjusted to a specified content ofconstituents with known therapeutic activities (e.g. sennosides). Naturalconcomitants are present. 标准提取物，具有一定含量的已知治疗活性成分（例如番泻苷）。伴有附随产物。 g) Quantified extracts with a specified content of constituentsconsidered as active markers (e.g. quantified Hypericum extracts). Naturalconcomitants are present. 具有一定含量的作为活性标记物的量化提取物（例如量化贯叶连翘提取物）。伴有附随产物。 h) Purified extracts neither standardised nor quantified for which thepattern of active constituents has to be determined. 既非标准提取物，也非量化提取物，其活性成分需进行确定的提取物。 A preparation of herbal origin may fall into morethan one of the above mentioned categories. Specific examples are reported inAnnex 1. 植物来源提取物也有可能是以上提及的分类中的多种类型。在附录1中有具体的例子。 5. CONCLUSIONS 结论 The definition of herbal preparations includes notonly extracts made by simple processes where the full spectrum of extractableplant constituents is present but also purified/refined extracts which mayconsist solely of mixtures of related herbal constituents. In the latter case,the full spectrum of plant constituents may no longer be present as certainconcomitant constituents have been removed in the purification processes. 草药加工品的定义不仅包含经简单加工的提取物（所有植物提取成分的图谱均可呈现），同样也包含纯化/精制提取物（这类提取物也许会只含有相关草药成分混合物）。对于后者，所有植物成分的图谱也许将不再呈现，因为在纯化过程中特定的附随成分已经被去除。 In some cases the purification of the herbal extract is sosubstantial that it is questionable whether the resulting preparation may stillbe considered as a highly purified herbal preparation or whether it should beregarded as an isolated herbal constituent or a mixture of closely relatedherbal constituents. The following aspects should be considered in designating theextract as a ‘herbal preparation': 在一些情况下提取纯化到了极致，以至于会产生这样的疑问：这类加工品还会被认为是高度纯化的草药加工品么？或者是否应被看做一个独立的草药成分或与之密切相关的成分混合物？ 在定义提取物为“草药加工品”时应考虑以下方面： 1. Definition is in accordance with Directive 2001/83/EC as amended andPh. Eur. 定义应满足修订的2001/83/EC法令和欧洲药典。 2. Complex mixture of constituents extracted from plant material ispresent in the preparation. 从植物中提取的复杂混合成分呈现在加工品中。 3. Proportional content of constituents in the preparation may varyfrom batch to batch due to the natural intrinsic variability. 加工品中各成分的含量比也许会由于其本身固有的变化性而导致每个批次间不同。 4. The preparation is a mixture of related constituents reflecting thenatural variability during the extraction process, but the mixture may bestandardised or quantified. 加工品是相关成分的混合物，在其加工过程中会呈现其本身的变化性，但最终的混合物也许是标准化的或定量化的。 At least one of the following criteria would excludethe material being designated as a ‘herbal preparation': 至少下列标准之一可排除物料被定义为“草药加工品”。 1. Extracts subjected to chemical processes where the chemicalmodifications may be comparable to a partial synthesis. These preparationsshould be assessed case by case. 提取物处于化学处理过程中，其化学修饰也许相当于局部合成。这类加工品应具体评估。 2. Extracts enriched with isolatedcompounds. 提取物含有大量的单独成分。 Some refined extracts can only be evaluated takinginto account additional information such as the manufacturing process. 考虑到其它情况下（如生产过程），一些精制提取物只能进行评估。
ANNEX 1 附录1 Examples consideredas herbal preparations 被认为草药加工品的例子 Example 1 例1 A highly concentrated ethyl acetate extract of milkthistle fruits (Silybummarianum) specified to contain 65% of silymarin according toPh. Eur., which is variable in its composition and contains between 20-45% ofsilycristin and silidianin, 40-65% silibinin A and B and 10-20% isosilibinin Aand B. The extract is standardised and assayed by: Silymarin, calculated as silibinin, related to the dried extract30-65% Sum of contents of silibinin A and silibinin B, calculated assilibinin with reference to total silymarin 40-60% Sum of contents of silicristin and silidianin, calculated assilibinin with reference to total silymarin 20-45% Isosilibin A and isosilibin B, calculated assilibinin with reference to total silymarin 10-20% 。 如，水飞蓟果实高浓度乙酸乙酯提取物（水飞蓟），根据欧洲药典其特定包含65%的水飞蓟素，水飞蓟素的成分是可变的，可包含20%-45%的水飞蓟丁和水飞蓟宁，40%-65%的水飞蓟宾A和B以及10%-20%的异水飞蓟宾A和B。提取物已被标准化，通过以下进行含量检测： 水飞蓟素，用水飞蓟宾计算，其干浸膏中为30-65% 水飞蓟宾A和B的总含量，用水飞蓟宾计算应为总水飞蓟素的40-60% 水飞蓟丁和水飞蓟宁的总含量，用水飞蓟宾计算应为总水飞蓟素的10-20% Example 2 例2 Extract of Serenoa repens. The herbal preparation is characterizedby: Free unsaturated and saturated fatty acids and respective methyl-and ethylesters, triglycerides, determined after methanolysis and calculated asthe sum of the derivatised fatty acids:85.0--95.0% Sterols: 0.2-0.4% Long chain alcohols: 0.15-0.30% 锯棕榈提取物。这类加工品的特征有： 甲醇分解后含有自由不饱和脂肪酸和饱和脂肪酸，以及各自的甲基乙酯、甲基甘油三酯，其用总衍生脂肪酸计算为含85%-95% 固醇类：0.2-0.4% 长链醇类：0.15-0.30% Example 3 例3 Ethanolic extract of soya beans. The extraction is followed bypurification steps (removal of lipids, filtration, preparative column). Theextract is characterised by isoflavones content of 36-44% with respect to driedextract. 大豆醇提取物。提取后进行纯化处理（去除脂类，过滤，制备柱）。这类提取物中（干浸膏）的异黄酮含量为36-44%， Example 4 例4 Deoiled, enriched phospholipids from soya beans. The phospholipidsare manufactured by hexane extraction of soya beans, purified (e.g. filtration,degumming, bleaching, hydration), enriched by ethanolic extraction andadsorption on a silica gel column. The obtained herbal preparation ischaracterised by phosphatidylcholine content of 73-79%. Other phospholipidspresent in preparation: phosphatidylethanolamine (max. 7%),phosphatidylinositol (max. 0.5%) and phosphatidic acid. 大豆去油后富含的磷脂质，这类物质为大豆进行己烷提取，纯化（例如过滤，脱胶，退色，水合），再通过乙醇充分提取和硅胶柱吸附。最终得到的提取物用卵磷脂含量表现为73-79%。加工品中的其它磷脂质：胆胺磷脂（最多为7%），肌醇磷脂（最多为0.5%）以及磷脂酸。 Example 5 例5 A mixture of isolated flavones manufactured by water extraction ofScullcap Baical (Scutellariabaicalensis) and purificated (filtration,acidification, ethanolic extraction). The extract is characterised by baicalincontent min. 75%. Other flavones present in the extract: baicalein and wogonin. 黄芩经过水提后进行纯化（过滤，酸化，醇提）得到的黄酮类混合物提取物。这类提取物用黄芩苷含量表现应不少于75%。提取物中其它黄酮类有：黄芩素和次黄芩素。 Example 6 例6 Aescin is a mixture of over 30 related saponins, manufactured bymethanolic extraction of horse chestnut seeds with subsequent purification (acidification,activated charcoal, crystallisation, dissolution in ethanol and drying).Purity: 96-103%. 七叶皂苷是超过30种相关皂苷的混合物，其是马栗种子经甲醇提取并纯化（酸化，活性炭，结晶，乙醇中分解及干燥）。纯度为96-103%。 Examples not considered as herbal preparations 不被认为草药加工品的例子 Example 7 Mixtures of active constituents derived by chemical treatment ofnatural compounds with methanesulfonic acid such as e.g. ergoloid mesylates. 通过使用甲磺酸对天然化合物进行化学处理得到的活性成分混合物，例如甲磺酸二氢麦角碱。 Justification: This preparation is not a herbal preparation because the chemicaltreatment is comparable to a partial synthesis (criterion of exclusion 1) andhas to be treated as a chemically defined mixture of active constituents. 理由：这不属于草药加工品，原因是其化学处理相当于部分合成过程，因此应认定为化学确定活性成分混合物。 Example 8 Calcium sennosides from senna leaves and/or pods. The plant material is extracted andthe extract is evaporated and concentrated. The dry extract is subjected tochromatographic or other appropriate purification methods to separate therefined extract containing the hydroxyanthracenic glycosides (sennosides). Thesennosides are precipitated as calcium sennosides by using a calcium saltsolution. The precipitate is dried to obtain the final calcium sennosidesmixture (NLT calcium sennosides 80% calculated as a content of sennosides NLT60%). 从番泻叶中得到的番泻苷钙。这类植物经过提取，其提取物经过蒸发和浓缩。干浸膏经过色谱分离或其它适当的纯化方法来分离得到精制后的提取物，这类提取物即包含番泻苷。番泻苷经过钙盐溶解沉淀，并经干燥最终得到番泻苷钙混合物（番泻苷钙不低于80%，即用番泻苷含量计算应不低于60%） Justification: This preparation is not a herbal preparation, because the finalcalcium sennosides mixture no longer contains the matrix of naturalconcomitants and therefore meets the criterion of exclusion 1. 理由：这类加工品并不属于草药加工品，因为最终的番泻苷钙混合物不再具有附随产物，因此符合exclusion1中的标准。 Examples for borderline cases 非典型个案 The following example can a priorineither be allocated to herbal preparations or pure substances using generalinclusion/exclusion criteria without additional information on themanufacturing process。 以下例子用通用的标准既不属于草药加工品也不属于纯物质，对生产过程也无更多的信息。 Example 10 例10 Curcuminoidsextracted and purified from turmeric: the active substance is not a singlechemically defined constituent but a mixture of 3 related constituents in aratio which can vary within a certain range. Purity 95.0-100.0% curcuminoidscalculated as sum of: Desmethoxycurcumin:15-25% Bidesmethoxycurcumin: 2.5-6.5% Curcumin:70-80% 从姜黄中提取和纯化得到的姜黄素：其活性物质不是单一的化学确定成分，而是3种成分的混合物，这3种成分的比例在一定范围内变化。纯度为95.0-100.0%的姜黄素用脱甲氧基姜黄素、双去甲氧基姜黄素和姜黄色素计算： 脱甲氧基姜黄素：15-25% 双去甲氧基姜黄素：2.5-6.5% 姜黄色素：70-80%
[1] Directive 2001/83/EC as amended
[2] CPMP/QWP/2819/00 Rev 1 Guideline on Quality ofHerbal Medicinal Products/Traditional Herbal Medicinal Products; “Productscontaining chemically defined isolated constituents or a mixture thereof arenot herbal medicinal products.”
[3] CHMP/QWP/297/97 Rev 1 Summary of Requirementsfor Active Substances in the Quality Part of the Dossier CPMP/QWP/130/96 Rev. 1Chemistry of New Active Substances. CPMP/ICH/2737/99-ICH Q3A (R2)Impurities Testing: Impurities in New Drug Substances (ICH Q3A) CPMP/ICH/367/96-ICH Q6ASpecifications: Test Procedures and Acceptance Criteria for New Drug Substancesand New Drug Products: Chemical Substances (ICH Q6A) EuropeanPharmacopoeia General Monograph “Substances for pharmaceutical use”01/2008:2034 EuropeanPharmacopoeia General Chapter “Control of impurities in substances forpharmaceutical use” (5.10) 01/2008:51000
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发表于 2016-5-29 10:28:27
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