WO2021109923A1 - Safe, effective and high-quality chinese medicine development platform system and realization method - Google Patents

Safe, effective and high-quality chinese medicine development platform system and realization method Download PDF

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WO2021109923A1
WO2021109923A1 PCT/CN2020/132027 CN2020132027W WO2021109923A1 WO 2021109923 A1 WO2021109923 A1 WO 2021109923A1 CN 2020132027 W CN2020132027 W CN 2020132027W WO 2021109923 A1 WO2021109923 A1 WO 2021109923A1
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quality
effective
platform system
safe
chinese medicine
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王梅
孙朋悦
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深圳市开物成务中医药科技有限公司
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    • G—PHYSICS
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    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B15/00—ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
    • G16B15/30—Drug targeting using structural data; Docking or binding prediction
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B40/00—ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B50/00—ICT programming tools or database systems specially adapted for bioinformatics
    • G16B50/30—Data warehousing; Computing architectures
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    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16C—COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE
    • G16C20/00—Chemoinformatics, i.e. ICT specially adapted for the handling of physicochemical or structural data of chemical particles, elements, compounds or mixtures
    • G16C20/50—Molecular design, e.g. of drugs
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16C—COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE
    • G16C20/00—Chemoinformatics, i.e. ICT specially adapted for the handling of physicochemical or structural data of chemical particles, elements, compounds or mixtures
    • G16C20/70—Machine learning, data mining or chemometrics
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16C—COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE
    • G16C20/00—Chemoinformatics, i.e. ICT specially adapted for the handling of physicochemical or structural data of chemical particles, elements, compounds or mixtures
    • G16C20/90—Programming languages; Computing architectures; Database systems; Data warehousing

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  • the invention relates to the technical field of plant medicine production and development, and more specifically, to a safe, effective, and high-quality Chinese medicine development platform system and an implementation method.
  • Botanicals are medicines used for medical purposes by part or all of plants. They are divided into traditional botanicals and modern botanicals. Plant extracts produced by modern science and technology are modern botanicals; botanicals can be divided into: whole (crude) Extracts-effective parts-effective components (active combination)-effective ingredients and other four levels, each level has the possibility of developing into medicines; the West is used to call botanicals natural medicines, the European Community
  • the defined botanical product is not just a single medicinal plant, it can be a combination of multiple herbal medicines (HERBAL MEDICAL PRODUCTS), containing specific plant active ingredients or plant extracts, and is used for medical purposes.
  • the technical problem to be solved by the present invention is to provide a safe, effective and high-quality Chinese medicine development platform system and an implementation method for the above-mentioned defects of the prior art.
  • a safe, effective, and high-quality Chinese medicine development platform system which includes a drug quality monitoring unit that monitors the quality of botanicals from the planting source, a multi-dimensional pharmacological unit that obtains or discovers drug activity data, and obtains clinical efficacy The clinical efficacy unit of the data.
  • the medicine quality monitoring unit includes a plant variety database.
  • the plant variety database is used to identify and identify each plant component for making botanicals.
  • the drug quality monitoring unit includes an extract and a mixture database
  • the extract and mixture database is used to extract various plant components for making botanicals Identification and identification of mixtures of substances and extracts.
  • the method for analyzing the quality of botanicals by the medicine quality monitoring unit includes fingerprint and/or statistics.
  • the multidimensional pharmacology unit includes a multivariate analysis unit, and the multivariate analysis unit is used to determine the effect of a multi-component botanical mixture on a set of living systems. The impact of the biological characteristics of the disease.
  • the method used when the multivariate analysis unit performs the determination is as follows:
  • step (c) Use multivariate analysis to determine the expected impact of the composition of the multi-component mixture sample shown in step (b) on the biological characteristics of the disease;
  • step (d) Use multivariate analysis in step (c) to determine the effective natural components or groups of natural components and their respective concentrations required to produce the expected effects on the biological characteristics of the disease.
  • the safe, effective and high-quality Chinese medicine development platform system of the present invention wherein the multi-analysis unit also includes a method when performing determination:
  • step (e) Prepare one or more natural product mixtures based on the information obtained in step (d), and predict the expected impact of these mixtures on the biological characteristics of the disease;
  • step (f) Determine the effect of the multi-component mixture prepared in step (e) on the biological characteristics of the disease.
  • the safe, effective and high-quality Chinese medicine development platform system of the present invention wherein the multi-dimensional pharmacology unit includes a biomarker tracking unit, and the biomarker tracking unit is used to continuously track the metabolite markers of the disease And feedback the status of the marker.
  • the clinical efficacy unit communicates with an external clinical trial institution to obtain clinical trial data for botanical drugs by the clinical trial institution.
  • a safe, effective and high-quality Chinese medicine development platform system implementation method is as follows:
  • the system biology technology platform of the present application can establish a quality control system starting from the source of the drug, and provide whole-process quality control for the safety and effectiveness of botanicals; it can prove the effectiveness of the complex components of botanicals, Drugs provide scientific basis; it can determine the metabolite markers of diseases, and provide scientific diagnostic methods for the dialectical treatment of botanicals; it can also detect the regulatory relationship between metabolites and different prescriptions, and provide a molecular level for the optimization of botanical formulas. in accordance with.
  • Figure 1 It is a schematic block diagram of a safe, effective and high-quality Chinese medicine development platform system for the implementation of the present invention
  • the safe, effective, and high-quality Chinese medicine development platform system of the implementation case of the present invention includes a drug quality monitoring unit 1 that monitors the quality of botanicals from the planting source, and obtains or discovers multi-dimensional pharmacology of drug activity data Unit 2, and clinical efficacy unit 3 for obtaining clinical efficacy data.
  • the system biology technology platform of this application can establish a quality control system that manages from the source of the drug, and provide process quality control for the safety and effectiveness of botanicals; it can prove the effectiveness of complex components of botanicals and provide scientific basis for botanicals; Determining the metabolite markers of the disease provides scientific diagnostic methods for the dialectical treatment of botanicals; it can also detect the regulatory relationship between metabolites and different prescriptions, and provide a basis for the optimization of botanical formulas at the molecular level.
  • the drug quality monitoring unit includes a plant variety database.
  • the plant variety database is used to identify and identify the plant components used to make botanicals;
  • the plant variety database data of the platform can be compared to verify the authenticity and quality level of plant components to ensure the quality of plant components. reliable.
  • the drug quality monitoring unit includes an extract and a mixture database, and the extract and mixture database is used to identify and identify the extracts of various plant components and the mixtures of the extracts used to make the botanical medicine.
  • the data of color, transparency, and sedimentation state can be collected and uploaded offline, and the data can be compared by the extract and mixture database of the platform. Ensure the reliable quality of the extracts of plant components and the mixture of extracts.
  • the method for analyzing the quality of the botanical by the drug quality monitoring unit includes fingerprint and/or statistics.
  • the multidimensional pharmacology unit includes a multivariate analysis unit.
  • the multivariate analysis unit is used to determine the effect of a multi-component botanical mixture on the biological characteristics of a group of diseases in a living system.
  • the method used in the multivariate analysis unit for determination is as follows:
  • step (c) Use multivariate analysis to determine the expected impact of the composition of the multi-component mixture sample shown in step (b) on the biological characteristics of the disease;
  • step (d) Use multivariate analysis in step (c) to determine the effective natural components or groups of natural components and their respective concentrations required to produce the expected impact on the biological characteristics of the disease.
  • the multivariate analysis unit also includes a method when performing the determination:
  • step (e) Prepare one or more natural product mixtures based on the information obtained in step (d), and predict the expected impact of these mixtures on the biological characteristics of the disease;
  • step (f) Determine the effect of the multi-component mixture prepared in step (e) on the biological characteristics of the disease.
  • a multi-component botanical medicine mixture can be developed within a prescribed quality range. Due to different culture conditions, the quality of each natural component or group of natural components may be locally different. If one or more natural components or one or more groups of natural components do not have the required quality, the multi-component mixture can be adjusted for one or more natural components or groups of natural components in order to achieve the desired pairing. The effect of the biological characteristics of the disease.
  • it can be determined by adjusting the amount of one or more natural components or one or more groups of natural components, so as to obtain the required amount of one or more natural components or one or more groups of natural components. Concentration to ensure that the multi-component mixture will have the expected impact on the biological characteristics of the disease.
  • a multi-component botanical mixture is a botanical component or a mixture of botanical components, which is produced not through chemical synthesis but through natural processes.
  • a multi-component herbal mixture will contain two or more herbs, and these herbs may contain many different ingredients.
  • MDP Multidimensional Pharmacology
  • the above method is not limited to only measuring the biological effects and synergistic effects in the mammalian system, and can also solve all possible biological system forms, including complex compounds from the same life combination.
  • the body fluid characteristics of plasma samples from the control group (reference group) and patient group (biometric disease symptom group) can be used to measure as many components as possible and to evaluate a single group between the two groups.
  • biomarkers/surrogate markers detect new biomarkers/surrogate markers, predict toxicological or pharmacological reactions, or develop new intervention pathways.
  • the biological characteristics to be determined in step (a) preferably include one or more of metabolism, gene expression and/or protein characteristics, and a combination of these characteristics can also be used.
  • step (a) priority is given to determining the biological characteristics of at least one body fluid or at least one tissue.
  • step (a) one or more of the following biomarkers are used to determine biological characteristics: genes, transcripts, proteins, metabolites, and (trace) elements.
  • step (b) at least one spectrometric technique, at least one based on electronic transition technique or at least one chromatographic technique is preferably used to determine the influence of a series of samples of the multi-component mixture on the biological characteristics of the disease.
  • step (c) at least one spectrometric technique, at least one based on electronic transition technique or at least one chromatographic technique is preferably used to determine the composition of the sample.
  • step (d) at least one spectrometric technique, at least one technique based on electronic transition or at least one chromatographic technique is preferably used to identify the effective components or component groups and their respective concentration.
  • step (f) at least one spectrometric technique, at least one technique based on electronic transition or at least one chromatographic technique is preferably used to identify the effective components or component groups required to affect the organism and their respective concentration.
  • the multi-component mixture used in the present invention can be any multi-component mixture that has a (potential) effect on the biological characteristics of the disease.
  • This multi-component mixture can be any botanical.
  • At least one spectrometry technique is preferably used.
  • the nuclear magnetic resonance technique (“NMR”) or mass spectrometry technique (“MS”) can be suitably used, with the latter technique focusing on a limited number of small molecule compounds.
  • Small molecule compounds include but are not limited to lipids, steroids, amino acids, organic acids, bile acids, eicosanoids, peptides, carbohydrates and trace elements.
  • At least nuclear magnetic resonance technology and/or mass spectrometry technology are preferably used, and mass spectrometry technology is preferred in the field of protein analysis (proteomics).
  • NMR sample preparation can usually be very simple to use freeze-drying and reconstruction in D2O, because the focus is on high-concentration components, that is, typical concentrations >100 ng/ml.
  • sample preparation methods can be used, for example, using polarity-based methods or derivatization methods for GC-MS and LC-MS.
  • spectral data obtained from one or more platforms can be used, including but not limited to mass spectrometry, nuclear magnetic resonance, liquid chromatography ( "LC"), gas chromatography (“GC”), high performance liquid chromatography (“HPLC”), capillary electrophoresis (“CE”), and any known form of coupling in low-resolution or high-resolution mode
  • mass spectrometry such as LC-MS, GC-MS, CE-MS, LC-UV, MS-MS, MSn, etc.
  • component-specific detectors such as laser-induced fluorescence and electrochemical detection, various typical data can also be obtained.
  • spectral data includes data from any spectrometric or chromatographic technique.
  • Spectrometry techniques include but are not limited to nuclear magnetic resonance spectroscopy, infrared spectroscopy, Raman spectroscopy and ultraviolet spectroscopy, and others also include mass spectroscopy.
  • Chromatography techniques include but are not limited to liquid chromatography, gas chromatography and electrophoresis.
  • the multi-dimensional pharmacology unit includes a biomarker tracking unit, and the biomarker tracking unit is used to continuously track the metabolite marker of the disease and feed back the status of the marker;
  • biomarkers are defined as features that are objectively measured and evaluated: normal biological processes, pathogenic processes, or pharmacological responses to therapeutic interventions.
  • Biomarkers can be genes, transcripts, proteins, metabolites (trace elements) or any combination of these components.
  • the clinical efficacy unit maintains contact with an external clinical trial institution to obtain clinical trial data for botanicals by the clinical trial institution.
  • a plant-to-patient system biology method according to the above-mentioned safe, effective and high-quality Chinese medicine development platform system, its realization method is as follows:
  • the system biology technology platform of this application can establish a quality control system starting from the source of the drug, and provide full quality management for the safety and effectiveness of botanicals; it can prove the effectiveness of the complex components of botanicals, and provide scientific basis for botanicals; it can determine the disease
  • the metabolite markers provide scientific diagnostic methods for the dialectical treatment of botanicals; it can also detect the regulatory relationship between metabolites and different prescriptions, and provide a basis for the optimization of botanical formulas at the molecular level.

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Abstract

A safe, effective and high-quality Chinese medicine development platform system and a realization method therefor. The platform system comprises: a medicine quality monitoring unit (1) for monitoring the quality of botanical medicine from a planting source, a multi-dimensional pharmacology unit (2) for acquiring or discovering medicine activity effect data, and a clinical curative effect unit (3) for acquiring clinical curative effect data. The platform system can establish a quality control system starting from a medicine source, thereby providing whole-process quality management for the safety and effectiveness of botanical medicine; can prove the effectiveness of complex components of the botanical medicine, thereby providing a scientific basis for the clinical application of the botanical medicine; can determine metabolite markers of diseases, thereby providing scientific diagnosis means for the dialectical treatment of the botanical medicine; and can also ascertain a regulation and control relationship between metabolites and different prescriptions, thereby providing a basis for the optimization of botanical medicine formulas at a molecular level.

Description

一种安全、有效、高质量中药开发平台系统及实现方法A safe, effective and high-quality traditional Chinese medicine development platform system and implementation method 技术领域Technical field
本发明涉及植物药生产开发技术领域，更具体地说，涉及一种安全、有效、高质量中药开发平台系统及实现方法。The invention relates to the technical field of plant medicine production and development, and more specifically, to a safe, effective, and high-quality Chinese medicine development platform system and an implementation method.
背景技术Background technique
植物药是以植物的部分或者全体用于医疗目的的医药品，分为传统植物药和现代植物药，运用现代科学技术生产的植物提取物为现代植物药；植物药可分成：全(粗)提物——有效部位——有效组分(活性组合)——有效成分等四个层次，每个层次都有开发成药物的可能；西方习惯于将植物药称为天然药物，欧共体所定义的植物药产品不只是单一药用植物，可以是多种植物药配伍(HERBAL MEDICAL PRODUCTS)，含有专一植物活性成分或是植物提取物，被运用于医疗目的的医药用品。Botanicals are medicines used for medical purposes by part or all of plants. They are divided into traditional botanicals and modern botanicals. Plant extracts produced by modern science and technology are modern botanicals; botanicals can be divided into: whole (crude) Extracts-effective parts-effective components (active combination)-effective ingredients and other four levels, each level has the possibility of developing into medicines; the West is used to call botanicals natural medicines, the European Community The defined botanical product is not just a single medicinal plant, it can be a combination of multiple herbal medicines (HERBAL MEDICAL PRODUCTS), containing specific plant active ingredients or plant extracts, and is used for medical purposes.
目前植物药的生产开发没有一个系统的平台，以能够将植物药的有效性、安全性和质量控制联系起来。At present, there is no systematic platform for the production and development of botanicals to link the effectiveness, safety and quality control of botanicals.
发明内容Summary of the invention
本发明要解决的技术问题在于，针对现有技术的上述缺陷，提供一种安全、有效、高质量中药开发平台系统及实现方法。The technical problem to be solved by the present invention is to provide a safe, effective and high-quality Chinese medicine development platform system and an implementation method for the above-mentioned defects of the prior art.
本发明解决其技术问题所采用的技术方案是：The technical solutions adopted by the present invention to solve its technical problems are:
构造一种安全、有效、高质量中药开发平台系统，其中，包括从种植源头对植物药的质量进行监控的药物质量监测单元、获取或发现药物活性作用数据的多维药理学单元，以及获取临床疗效数据的临床疗效单元。Construct a safe, effective, and high-quality Chinese medicine development platform system, which includes a drug quality monitoring unit that monitors the quality of botanicals from the planting source, a multi-dimensional pharmacological unit that obtains or discovers drug activity data, and obtains clinical efficacy The clinical efficacy unit of the data.
本发明所述的安全、有效、高质量中药开发平台系统，其中，所述药物质量监测单元包括植物品种数据库。所述植物品种数据库用于对制作植物药的各植物组分进行鉴定识别。In the safe, effective and high-quality Chinese medicine development platform system of the present invention, the medicine quality monitoring unit includes a plant variety database. The plant variety database is used to identify and identify each plant component for making botanicals.
本发明所述的安全、有效、高质量中药开发平台系统，其中，所述药物质量监测单元包括提取物及混合物数据库，所述提取物及混合物数据库用于对制作植物药的各植物组分提取物以及提取物的混合物进行鉴定识别。The safe, effective and high-quality traditional Chinese medicine development platform system of the present invention, wherein the drug quality monitoring unit includes an extract and a mixture database, and the extract and mixture database is used to extract various plant components for making botanicals Identification and identification of mixtures of substances and extracts.
本发明所述的安全、有效、高质量中药开发平台系统，其中，所述药物质量监测单元进行植物药的质量分析方法包括指纹图谱和/或统计学。In the safe, effective and high-quality Chinese medicine development platform system of the present invention, the method for analyzing the quality of botanicals by the medicine quality monitoring unit includes fingerprint and/or statistics.
本发明所述的安全、有效、高质量中药开发平台系统，其中，所述多维药理学单元包括多元分析单元，所述多元分析单元用于测定多组分植物药混合物对一组生命系统内的疾病的生物学特征的影响。The safe, effective and high-quality traditional Chinese medicine development platform system of the present invention, wherein the multidimensional pharmacology unit includes a multivariate analysis unit, and the multivariate analysis unit is used to determine the effect of a multi-component botanical mixture on a set of living systems. The impact of the biological characteristics of the disease.
本发明所述的安全、有效、高质量中药开发平台系统，其中，所述多元分析单元进行测定时采用方法如下：In the safe, effective, and high-quality Chinese medicine development platform system of the present invention, the method used when the multivariate analysis unit performs the determination is as follows:
(a)将一组有疾病症状的生命系统的生物学特征与对照的或健康的生命系统组的生物学特征进行比较，确定疾病的生物学特征；(a) Compare the biological characteristics of a group of life systems with disease symptoms with those of a control or healthy life system group to determine the biological characteristics of the disease;
(b)采用多元分析法测定多组分混合物的一系列样品对疾病生物学特征的影响，其中样品中一种或多种天然成分或一组或多组天然成分的浓度不同；(b) Using a multivariate analysis method to determine the effect of a series of samples of a multi-component mixture on the biological characteristics of the disease, in which the concentration of one or more natural ingredients or one or more groups of natural ingredients in the samples is different;
(c)使用多元分析确定步骤(b)中所示的多组分混合物样品的组成对疾病生物学特征的预期影响；(c) Use multivariate analysis to determine the expected impact of the composition of the multi-component mixture sample shown in step (b) on the biological characteristics of the disease;
(d)使用多元分析在步骤(c)中确定有效的自然组分或自然组分组及其 对疾病生物学特征产生预期影响所需的各自浓度。(d) Use multivariate analysis in step (c) to determine the effective natural components or groups of natural components and their respective concentrations required to produce the expected effects on the biological characteristics of the disease.
本发明所述的安全、有效、高质量中药开发平台系统，其中，所述多元分析单元进行测定时还包括方法：The safe, effective and high-quality Chinese medicine development platform system of the present invention, wherein the multi-analysis unit also includes a method when performing determination:
(e)根据步骤(d)中获得的信息制备一组或多组分天然产品混合物，预测这些混合物会对疾病的生物学特征产生的预期影响；(e) Prepare one or more natural product mixtures based on the information obtained in step (d), and predict the expected impact of these mixtures on the biological characteristics of the disease;
(f)测定步骤(e)中制备的多组分混合物对疾病生物学特性的影响。(f) Determine the effect of the multi-component mixture prepared in step (e) on the biological characteristics of the disease.
本发明所述的安全、有效、高质量中药开发平台系统，其中，所述多维药理学单元包括生物标志物追踪单元，所述生物标志物追踪单元用于对病症的代谢物标志物进行连续追踪并反馈标志物状态。The safe, effective and high-quality Chinese medicine development platform system of the present invention, wherein the multi-dimensional pharmacology unit includes a biomarker tracking unit, and the biomarker tracking unit is used to continuously track the metabolite markers of the disease And feedback the status of the marker.
本发明所述的安全、有效、高质量中药开发平台系统，其中，所述临床疗效单元与外部的临床试验机构进行通讯，获取临床试验机构针对植物药临床试验数据。According to the safe, effective and high-quality Chinese medicine development platform system of the present invention, the clinical efficacy unit communicates with an external clinical trial institution to obtain clinical trial data for botanical drugs by the clinical trial institution.
一种安全、有效、高质量中药开发平台系统实现方法，根据上述的安全、有效、高质量中药开发平台系统，实现方法如下：A safe, effective and high-quality Chinese medicine development platform system implementation method. According to the above-mentioned safe, effective and high-quality Chinese medicine development platform system, the implementation method is as follows:
对制作植物药中植物组分的特征、植物组分提取物以及各提取物的混合物进行质量监管；Supervise the quality of the characteristics of plant components, plant component extracts and mixtures of various extracts in the production of botanicals;
对制成后的植物药的药物活性作用进行多元化分析，并对病症的代谢物标志物进行连续追踪；Perform diversified analysis of the drug activity of the finished botanicals, and continuously track the metabolite markers of the disease;
对植物药的临床实验进行追踪。Follow up the clinical trials of botanicals.
本发明的有益效果在于：本申请的系统生物学技术平台可以建立从药物源头开始的质量控制体系，为植物药的安全有效提供全过程质量控制；能证明植物药复杂成分的有效性，为植物药提供科学依据；能确定病症的代谢物标志物，为植物药的辩证治疗提供科学的诊断手段；还可以探明代谢物与不同方剂的调 控关系，为植物药配方的优化在分子水平上提供依据。The beneficial effects of the present invention are: the system biology technology platform of the present application can establish a quality control system starting from the source of the drug, and provide whole-process quality control for the safety and effectiveness of botanicals; it can prove the effectiveness of the complex components of botanicals, Drugs provide scientific basis; it can determine the metabolite markers of diseases, and provide scientific diagnostic methods for the dialectical treatment of botanicals; it can also detect the regulatory relationship between metabolites and different prescriptions, and provide a molecular level for the optimization of botanical formulas. in accordance with.
附图说明Description of the drawings
为了更清楚地说明本发明实施案例或基于现有技术的技术方案，下面将结合附图及实施案例对本发明作进一步说明。下面的附图仅仅是本发明的部分实施案例，对于本领域技术人员来讲，根据这些附图可以获得更多的收获。In order to more clearly illustrate the implementation cases of the present invention or the technical solutions based on the prior art, the present invention will be further described below with reference to the accompanying drawings and implementation cases. The following drawings are only part of the implementation cases of the present invention. For those skilled in the art, more gains can be obtained from these drawings.
图1.是本发明实施案例的安全、有效、高质量中药开发平台系统原理框图；Figure 1. It is a schematic block diagram of a safe, effective and high-quality Chinese medicine development platform system for the implementation of the present invention;
图2.通过系统药物反应指纹图谱发现多因素干预方案(左)并与疾病系统生物标记物进行比较(右)和关联起来，寻找新的生物标记和治疗靶点；Figure 2. Discovery of multi-factor intervention programs (left) through systemic drug response fingerprints and compare them with disease system biomarkers (right) and correlate them to find new biomarkers and therapeutic targets;
图3.药物在慢性病动物模型的系统反应图谱；Figure 3. System response map of drugs in animal models of chronic diseases;
图4.系统生物学实验测量的疾病生物标志物相关网络：组合药物干预设计的基础。Figure 4. Disease biomarker-related networks measured by experiments in systems biology: the basis for the design of combinatorial drug interventions.
具体实施方式Detailed ways
为了使本发明实施案例的目的、技术方案和优点更加清楚，下面将结合本发明实施案例中的技术方案进行清楚、完整的描述，显然，所描述的实施案例是本发明的部分内容，而不是全部。基于本发明的实施案例，本领域普通技术人员在没有付出创造性劳动的前提下所获得的所有其他实施案例，都属于本发明的保护范围。In order to make the purpose, technical solutions and advantages of the implementation cases of the present invention clearer, a clear and complete description will be given below in conjunction with the technical solutions in the implementation cases of the present invention. Obviously, the described implementation cases are part of the content of the present invention, not All. Based on the implementation cases of the present invention, all other implementation cases obtained by those of ordinary skill in the art without creative work shall fall within the protection scope of the present invention.
本发明实施案例的安全、有效、高质量中药开发平台系统，如图1所示，包括从种植源头对植物药的质量进行监控的药物质量监测单元1，获取或发现药物活性作用数据的多维药理学单元2，以及获取临床疗效数据的临床疗效单 元3。本申请的系统生物学技术平台可以建立从药物源头开始管理的质量控制体系，为植物药的安全有效提供过程的质量控制；能证明植物药复杂成分的有效性，为植物药提供科学依据；能确定病症的代谢物标志物，为植物药的辩证治疗提供科学的诊断手段；还可以探明代谢物与不同方剂的调控关系，为植物药配方的优化在分子水平上提供依据。The safe, effective, and high-quality Chinese medicine development platform system of the implementation case of the present invention, as shown in Figure 1, includes a drug quality monitoring unit 1 that monitors the quality of botanicals from the planting source, and obtains or discovers multi-dimensional pharmacology of drug activity data Unit 2, and clinical efficacy unit 3 for obtaining clinical efficacy data. The system biology technology platform of this application can establish a quality control system that manages from the source of the drug, and provide process quality control for the safety and effectiveness of botanicals; it can prove the effectiveness of complex components of botanicals and provide scientific basis for botanicals; Determining the metabolite markers of the disease provides scientific diagnostic methods for the dialectical treatment of botanicals; it can also detect the regulatory relationship between metabolites and different prescriptions, and provide a basis for the optimization of botanical formulas at the molecular level.
采用本发明技术方案，可以实现基于植物为基础的药物的开发和质量控制。By adopting the technical scheme of the present invention, the development and quality control of plant-based medicines can be realized.
优选的，药物质量监测单元包括植物品种数据库。植物品种数据库用于对制作植物药的各植物组分进行鉴定识别；Preferably, the drug quality monitoring unit includes a plant variety database. The plant variety database is used to identify and identify the plant components used to make botanicals;
可根据植物组分的形状、气味、色泽等进行线下采集后上传，依靠平台的植物品种数据库数据进行比对，验证植物组分的真伪、质量等级等属性，以保障植物组分的质量可靠。According to the shape, smell, color, etc. of plant components, they can be collected offline and uploaded. The plant variety database data of the platform can be compared to verify the authenticity and quality level of plant components to ensure the quality of plant components. reliable.
优选的，药物质量监测单元包括提取物及混合物数据库，提取物及混合物数据库用于对制作植物药的各植物组分提取物以及各提取物的混合物进行鉴定识别。Preferably, the drug quality monitoring unit includes an extract and a mixture database, and the extract and mixture database is used to identify and identify the extracts of various plant components and the mixtures of the extracts used to make the botanical medicine.
可对单一植物组分的提取物，也可以对多组分提取物的混合物，在线下进行色泽、透明度、沉降状态等数据采集后上传，依靠平台的提取物及混合物数据库进行数据比对，以保障植物组分的提取物以及提取物的混合物的质量可靠。For the extract of a single plant component, or for the mixture of multi-component extracts, the data of color, transparency, and sedimentation state can be collected and uploaded offline, and the data can be compared by the extract and mixture database of the platform. Ensure the reliable quality of the extracts of plant components and the mixture of extracts.
优选的，药物质量监测单元进行植物药的质量分析方法包括指纹图谱和/或统计学。Preferably, the method for analyzing the quality of the botanical by the drug quality monitoring unit includes fingerprint and/or statistics.
优选的，多维药理学单元包括多元分析单元。多元分析单元用于测定多组分植物药混合物对一组生命系统内的疾病的生物学特征的影响。Preferably, the multidimensional pharmacology unit includes a multivariate analysis unit. The multivariate analysis unit is used to determine the effect of a multi-component botanical mixture on the biological characteristics of a group of diseases in a living system.
优选的，多元分析单元进行测定时采用方法如下：Preferably, the method used in the multivariate analysis unit for determination is as follows:
(a)将一组有疾病症状的生命系统的生物学特征与参考的或健康的生命系统组的生物学特征进行比较，确定疾病的生物学特征；(a) Compare the biological characteristics of a group of life systems with disease symptoms with those of a reference or healthy life system group to determine the biological characteristics of the disease;
(b)采用多元分析法测定多组分混合物的一系列样品对疾病生物学特征的影响，其中样品中一种或多种天然成分或一组或多组天然成分的浓度不同；(b) Using a multivariate analysis method to determine the effect of a series of samples of a multi-component mixture on the biological characteristics of the disease, in which the concentration of one or more natural ingredients or one or more groups of natural ingredients in the samples is different;
(c)使用多元分析确定步骤(b)中所示的多组分混合物样品的组成对疾病生物学特征的预期影响；(c) Use multivariate analysis to determine the expected impact of the composition of the multi-component mixture sample shown in step (b) on the biological characteristics of the disease;
(d)使用多元分析在步骤(c)中确定有效的自然组分或自然组分组及其对疾病生物学特征产生预期影响所需的各自浓度。(d) Use multivariate analysis in step (c) to determine the effective natural components or groups of natural components and their respective concentrations required to produce the expected impact on the biological characteristics of the disease.
优选的，多元分析单元进行测定时还包括方法：Preferably, the multivariate analysis unit also includes a method when performing the determination:
(e)根据步骤(d)中获得的信息制备一组或多组分天然产品混合物，预测这些混合物会对疾病的生物学特征产生的预期影响；(e) Prepare one or more natural product mixtures based on the information obtained in step (d), and predict the expected impact of these mixtures on the biological characteristics of the disease;
(f)测定步骤(e)中制备的多组分混合物对疾病生物学特性的影响。(f) Determine the effect of the multi-component mixture prepared in step (e) on the biological characteristics of the disease.
采用本发明的技术方案，可以在规定的质量范围内开发多组分植物药混合物。由于培养条件不同，各个天然组分或天然组分组的质量可能局部不同。如果一个或多个天然组分或一组或多组天然组分不具有所需的质量，则可以针对一个或多个天然组分或天然组分组调节多组分混合物，以便达到所需的对疾病的生物学特征的效果。By adopting the technical scheme of the present invention, a multi-component botanical medicine mixture can be developed within a prescribed quality range. Due to different culture conditions, the quality of each natural component or group of natural components may be locally different. If one or more natural components or one or more groups of natural components do not have the required quality, the multi-component mixture can be adjusted for one or more natural components or groups of natural components in order to achieve the desired pairing. The effect of the biological characteristics of the disease.
例如，可以通过调节相应的一个或多个天然组分或一组或多组天然组分的量来确定，以便获得一个或多个天然组分或一种或多种组天然组分的所需浓度，确保多组分混合物会对疾病的生物学特征产生预期的影响。For example, it can be determined by adjusting the amount of one or more natural components or one or more groups of natural components, so as to obtain the required amount of one or more natural components or one or more groups of natural components. Concentration to ensure that the multi-component mixture will have the expected impact on the biological characteristics of the disease.
多组分植物药混合物为植物药组分或各植物药组分的混合物，该组分不是通过化学合成而是通过自然过程产生的。例如，多组分草药混合物将包含两种 或两种以上的草药，这些草药可能包含许多不同的成分。A multi-component botanical mixture is a botanical component or a mixture of botanical components, which is produced not through chemical synthesis but through natural processes. For example, a multi-component herbal mixture will contain two or more herbs, and these herbs may contain many different ingredients.
采用上述方法能够通过独特的方式测量多个目标的干预效果，以最佳的方式执行这些干预，揭示有效成分的生物学特征。除了可以揭示单一药物等简单干扰的影响外，还可以揭示使用多组分混合物的复杂干扰。例如，草药产品和功能性食品。这种独特的方法被称为多维药理学(MDP)，使用系统生物学方法，通过测量和整合代谢数据和其它方面的数据(如遗传和/或蛋白质组数据)来研究生物系统。Using the above method can measure the intervention effects of multiple targets in a unique way, implement these interventions in the best way, and reveal the biological characteristics of the active ingredients. In addition to revealing the influence of simple interferences such as single drugs, it can also reveal complex interferences using multi-component mixtures. For example, herbal products and functional foods. This unique method is called Multidimensional Pharmacology (MDP), which uses systems biology methods to study biological systems by measuring and integrating metabolic data and other data (such as genetic and/or proteomic data).
上述方法不限于仅仅测定在哺乳动物系统中的生物影响和协同影响，还可以解决所有可能的生物系统形式，包括来自同一生命组合的复杂化合物。The above method is not limited to only measuring the biological effects and synergistic effects in the mammalian system, and can also solve all possible biological system forms, including complex compounds from the same life combination.
在健康和疾病研究中，可以使用来自对照组(参照组)和患者组(具有生物特征的疾病症状组)的血浆样本的体液特征来测量尽可能多的组分并且评估两组之间单一组分或组分模式的差异，以便更好地了解潜在的生物学机制，检测新的生物标记物/替代标记物，预测毒理学或药理学反应或开发新的干预途径。In health and disease research, the body fluid characteristics of plasma samples from the control group (reference group) and patient group (biometric disease symptom group) can be used to measure as many components as possible and to evaluate a single group between the two groups To better understand the underlying biological mechanisms, detect new biomarkers/surrogate markers, predict toxicological or pharmacological reactions, or develop new intervention pathways.
在步骤(a)中待测定的生物学特征最好包括一种或多种代谢、基因表达和/或蛋白质特征，也可以使用是这些特征的组合。The biological characteristics to be determined in step (a) preferably include one or more of metabolism, gene expression and/or protein characteristics, and a combination of these characteristics can also be used.
在步骤(a)中，优先确定至少一种体液或至少一种组织的生物学特征。In step (a), priority is given to determining the biological characteristics of at least one body fluid or at least one tissue.
在步骤(a)中使用以下一个或多个生物标志物确定生物特征：基因、转录物、蛋白质、代谢物和(微量)元素。In step (a), one or more of the following biomarkers are used to determine biological characteristics: genes, transcripts, proteins, metabolites, and (trace) elements.
在步骤(b)中，优先使用至少一种光谱测定技术，至少一种基于电子跃迁技术或至少一种色谱技术来确定多组分混合物的一系列样品对疾病的生物学特征的影响。In step (b), at least one spectrometric technique, at least one based on electronic transition technique or at least one chromatographic technique is preferably used to determine the influence of a series of samples of the multi-component mixture on the biological characteristics of the disease.
在步骤(c)中，优先使用至少一种光谱测定技术，至少一种基于电子跃 迁技术或至少一种色谱技术来确定样品的组成。In step (c), at least one spectrometric technique, at least one based on electronic transition technique or at least one chromatographic technique is preferably used to determine the composition of the sample.
在步骤(d)中，优先使用至少一种光谱测定技术，至少一种基于电子跃迁的技术或至少一种色谱技术来鉴定对生物体产生影响所需的有效组分或组分组及其各自的浓度。In step (d), at least one spectrometric technique, at least one technique based on electronic transition or at least one chromatographic technique is preferably used to identify the effective components or component groups and their respective concentration.
在步骤(f)中，优先使用至少一种光谱测定技术，至少一种基于电子跃迁的技术或至少一种色谱技术来鉴定对生物体产生影响所需的有效组分或组分组及其各自的浓度。In step (f), at least one spectrometric technique, at least one technique based on electronic transition or at least one chromatographic technique is preferably used to identify the effective components or component groups required to affect the organism and their respective concentration.
本发明使用的多组分混合物可以是对疾病的生物学特征具有(潜在)影响的任何多组分混合物。这种多组分混合物可以是任何植物药。The multi-component mixture used in the present invention can be any multi-component mixture that has a (potential) effect on the biological characteristics of the disease. This multi-component mixture can be any botanical.
在步骤(a)-(d)和(f)(e)的每一步中，优先使用至少一种光谱测定技术。可以适当地使用核磁共振技术(“NMR”)或质谱技术(“MS”)，其中后一种技术集中于有限数量的小分子化合物。小分子化合物包括但不限于脂质，类固醇，氨基酸，有机酸，胆汁酸，类二十烷酸，肽，碳水化合物和微量元素。In each of steps (a)-(d) and (f)(e), at least one spectrometry technique is preferably used. The nuclear magnetic resonance technique ("NMR") or mass spectrometry technique ("MS") can be suitably used, with the latter technique focusing on a limited number of small molecule compounds. Small molecule compounds include but are not limited to lipids, steroids, amino acids, organic acids, bile acids, eicosanoids, peptides, carbohydrates and trace elements.
在步骤(a)-(d)和(f)(e)的每一步中，优先至少使用核磁共振技术和/或质谱技术，在蛋白质分析(蛋白质组学)领域优选质谱技术。In each of steps (a)-(d) and (f)(e), at least nuclear magnetic resonance technology and/or mass spectrometry technology are preferably used, and mass spectrometry technology is preferred in the field of protein analysis (proteomics).
以小分子的情况为例，核磁共振的样品制备通常可以非常简单地使用冷冻干燥和在D2O中重建，因为重点是高浓度组分，即典型浓度>100毫微克/毫升。对于质谱技术，可以使用多种样品制备方法，例如，使用基于极性的方法或用于GC-MS以及LC-MS的衍生化方法。Taking the case of small molecules as an example, NMR sample preparation can usually be very simple to use freeze-drying and reconstruction in D2O, because the focus is on high-concentration components, that is, typical concentrations >100 ng/ml. For mass spectrometry techniques, a variety of sample preparation methods can be used, for example, using polarity-based methods or derivatization methods for GC-MS and LC-MS.
在步骤(a)-(d)和(f)(e)的每一步中，可以使用从一个或多个平台获得的光谱数据，包括但不限于质谱技术、核磁共振技术、液相色谱法(“LC”)、气相色谱法(“GC”)、高效液相色谱法(“HPLC”)、毛细管电泳法(“CE”)，以及低分辨率或高分辨率模式的任何已知形式的联用质谱，如LC-MS，GC-MS， CE-MS，LC-UV，MS-MS，MSn等。通过使用更多组分特异性检测器，例如激光诱导荧光和电化学检测，也可以获得典型的各种数据。In each of steps (a)-(d) and (f)(e), spectral data obtained from one or more platforms can be used, including but not limited to mass spectrometry, nuclear magnetic resonance, liquid chromatography ( "LC"), gas chromatography ("GC"), high performance liquid chromatography ("HPLC"), capillary electrophoresis ("CE"), and any known form of coupling in low-resolution or high-resolution mode Use mass spectrometry, such as LC-MS, GC-MS, CE-MS, LC-UV, MS-MS, MSn, etc. By using more component-specific detectors, such as laser-induced fluorescence and electrochemical detection, various typical data can also be obtained.
如本文所用，术语“光谱数据”包括来自任何光谱测定或色谱技术的数据。光谱测定技术包括但不限于核磁共振光谱、红外光谱、拉曼光谱和紫外光谱，其它还包括质谱学。色谱技术包括但不限于液相色谱，气相色谱和电泳。As used herein, the term "spectral data" includes data from any spectrometric or chromatographic technique. Spectrometry techniques include but are not limited to nuclear magnetic resonance spectroscopy, infrared spectroscopy, Raman spectroscopy and ultraviolet spectroscopy, and others also include mass spectroscopy. Chromatography techniques include but are not limited to liquid chromatography, gas chromatography and electrophoresis.
优选的，多维药理学单元包括生物标志物追踪单元，生物标志物追踪单元用于对病症的代谢物标志物进行连续追踪并反馈标志物状态；Preferably, the multi-dimensional pharmacology unit includes a biomarker tracking unit, and the biomarker tracking unit is used to continuously track the metabolite marker of the disease and feed back the status of the marker;
在本申请的内容中，生物标志物被定义为客观测量和评估的特征：正常的生物过程、致病过程或对治疗干预的药理学反应。In the content of this application, biomarkers are defined as features that are objectively measured and evaluated: normal biological processes, pathogenic processes, or pharmacological responses to therapeutic interventions.
生物标记物可以是基因、转录物、蛋白质、代谢物(微量元素)或这些成分的任何组合。Biomarkers can be genes, transcripts, proteins, metabolites (trace elements) or any combination of these components.
优选的，临床疗效单元与外部的临床试验机构保持联系，获取临床试验机构针对植物药临床试验数据。Preferably, the clinical efficacy unit maintains contact with an external clinical trial institution to obtain clinical trial data for botanicals by the clinical trial institution.
一种植物到患者系统生物学方法，根据上述的安全、有效、高质量中药开发平台系统，其实现方法如下：A plant-to-patient system biology method, according to the above-mentioned safe, effective and high-quality Chinese medicine development platform system, its realization method is as follows:
对制作植物药中植物组分的特征、植物组分提取物以及各提取物的混合物进行质量监管；Supervise the quality of the characteristics of plant components, plant component extracts and mixtures of various extracts in the production of botanicals;
对制成后的植物药的药物活性作用进行多元化分析，并对病症的代谢物标志物进行连续追踪；Perform diversified analysis of the drug activity of the finished botanicals, and continuously track the metabolite markers of the disease;
对植物药的临床实验进行追踪；Tracking clinical trials of botanicals;
本申请的系统生物学技术平台可以建立从药物源头开始的质量控制体系，为植物药的安全有效提供全程质量管理；能证明植物药复杂成分的有效性，为植物药提供科学依据；能确定病症的代谢物标志物，为植物药的辩证治疗提供 科学的诊断手段；还可以探明代谢物与不同方剂的调控关系，为植物药配方的优化在分子水平上提供依据。The system biology technology platform of this application can establish a quality control system starting from the source of the drug, and provide full quality management for the safety and effectiveness of botanicals; it can prove the effectiveness of the complex components of botanicals, and provide scientific basis for botanicals; it can determine the disease The metabolite markers provide scientific diagnostic methods for the dialectical treatment of botanicals; it can also detect the regulatory relationship between metabolites and different prescriptions, and provide a basis for the optimization of botanical formulas at the molecular level.
应当理解的是，对本领域科技人员来说，可以根据上述说明加以改进或变换，而所有这些改进和变换都应属于本发明所附权利要求的保护范围。It should be understood that those skilled in the art can make improvements or changes based on the above description, and all these improvements and changes should fall within the protection scope of the appended claims of the present invention.

Claims (10)

  1. 一种安全、有效、高质量中药开发平台系统，其特征在于，包括：从种植源头对植物药的质量进行监控的药物质量监测单元，获取或发现药物活性作用数据的多维药理学单元，以及获取临床疗效数据的临床疗效单元。A safe, effective and high-quality traditional Chinese medicine development platform system, which is characterized by including: a drug quality monitoring unit that monitors the quality of botanicals from the planting source, a multi-dimensional pharmacology unit that obtains or discovers drug activity data, and obtains Clinical efficacy unit of clinical efficacy data.
  2. 根据权利要求1所述的安全、有效、高质量中药开发平台系统，其特征在于，所述药物质量监测单元包括：植物品种数据库，用于对制作植物药的各植物组分进行鉴定识别。The safe, effective, and high-quality Chinese medicine development platform system according to claim 1, wherein the medicine quality monitoring unit comprises: a plant variety database, which is used to identify and identify various plant components for making botanical medicines.
  3. 根据权利要求1所述的安全、有效、高质量中药开发平台系统，其特征在于，所述药物质量监测单元包括：提取物及混合物数据库，用于对制作植物药的各植物组分提取物以及各提取物的混合物进行鉴定识别。The safe, effective, and high-quality traditional Chinese medicine development platform system according to claim 1, wherein the drug quality monitoring unit includes: an extract and a mixture database, which is used for making botanical extracts and extracts of various plant components. The mixture of each extract is identified.
  4. 根据权利要求1-3任一所述的安全、有效、高质量中药开发平台系统，其特征在于，所述药物质量监测单元进行植物药的质量分析方法包括指纹图谱和/或统计学。The safe, effective, and high-quality Chinese medicine development platform system according to any one of claims 1 to 3, wherein the method for analyzing the quality of botanicals by the medicine quality monitoring unit includes fingerprint and/or statistics.
  5. 根据权利要求1所述的安全、有效、高质量中药开发平台系统，其特征在于，所述多维药理学单元包括：多元分析单元，用于测定多组分植物药混合物对一组生命系统内的疾病的生物学特征的影响。The safe, effective, and high-quality Chinese medicine development platform system according to claim 1, wherein the multi-dimensional pharmacology unit comprises: a multi-analysis unit for determining the effect of a multi-component botanical mixture on a group of living systems The impact of the biological characteristics of the disease.
  6. 根据权利要求5所述的安全、有效、高质量中药开发平台系统，其特征在于，所述多元分析单元进行测定时采用方法如下：The safe, effective, and high-quality Chinese medicine development platform system according to claim 5, wherein the method used when the multivariate analysis unit performs the determination is as follows:
    (a)将一组有疾病症状的生命系统的生物学特征与对照的或健康的生命系统组的生物学特征进行比较，确定疾病的生物学特征；(a) Compare the biological characteristics of a group of life systems with disease symptoms with those of a control or healthy life system group to determine the biological characteristics of the disease;
    (b)采用多元分析法测定多组分混合物的一系列样品对疾病生物学特征的影响，其中样品中一种或多种天然成分或一组或多组天然成分的浓度不同；(b) Using a multivariate analysis method to determine the effect of a series of samples of a multi-component mixture on the biological characteristics of the disease, in which the concentration of one or more natural ingredients or one or more groups of natural ingredients in the samples is different;
    (c)使用多元分析确定步骤(b)中所示的多组分混合物样品的组成对疾病生物学特征的预期影响；(c) Use multivariate analysis to determine the expected impact of the composition of the multi-component mixture sample shown in step (b) on the biological characteristics of the disease;
    (d)使用多元分析在步骤(c)中确定有效的自然组分或自然组分组及其对疾病生物学特征产生预期影响所需的各自浓度。(d) Use multivariate analysis in step (c) to determine the effective natural components or groups of natural components and their respective concentrations required to produce the expected impact on the biological characteristics of the disease.
  7. 根据权利要求6所述的安全、有效、高质量中药开发平台系统，其特征在于，所述多元分析单元进行测定时还包括方法：The safe, effective, and high-quality traditional Chinese medicine development platform system according to claim 6, wherein the multivariate analysis unit further includes a method when performing the determination:
    (e)根据步骤(d)中获得的信息制备一组或多组分天然产品混合物，预测这些混合物会对疾病的生物学特征产生的预期影响；(e) Prepare one or more natural product mixtures based on the information obtained in step (d), and predict the expected impact of these mixtures on the biological characteristics of the disease;
    (f)测定步骤(e)中制备的多组分混合物对疾病生物学特性的影响。(f) Determine the effect of the multi-component mixture prepared in step (e) on the biological characteristics of the disease.
  8. 根据权利要求1所述的安全、有效、高质量中药开发平台系统，其特征在于，所述多维药理学单元包括生物标志物追踪单元，所述生物标志物追踪单元用于对病症的代谢物标志物进行连续追踪并反馈标志物状态。The safe, effective, and high-quality traditional Chinese medicine development platform system according to claim 1, wherein the multi-dimensional pharmacology unit includes a biomarker tracking unit, and the biomarker tracking unit is used to identify metabolites of diseases. Continuous tracking of the object and feedback of the status of the marker.
  9. 根据权利要求1所述的安全、有效、高质量中药开发平台系统，其特征在于，所述临床疗效单元与外部的临床试验机构保持联系，获取临床试验机构针对植物药临床试验数据。The safe, effective, and high-quality traditional Chinese medicine development platform system according to claim 1, wherein the clinical efficacy unit maintains contact with an external clinical trial institution to obtain clinical trial data for botanicals by the clinical trial institution.
  10. 一种安全、有效、高质量中药开发平台系统的实现方法，根据权利要求1-9任一所述的平台系统，其特征在于，实现方法如下：A method for implementing a safe, effective, and high-quality Chinese medicine development platform system. The platform system according to any one of claims 1-9, characterized in that the implementation method is as follows:
    对制作植物药中植物组分的特征、植物组分提取物以及各提取物的混合物进行质量监管；Quality supervision of the characteristics of plant components, plant component extracts and mixtures of various extracts in the production of botanicals;
    对制成后的植物药的药物活性作用进行多元化分析，并对病症的代谢物标志物进行连续追踪；Diversified analysis of the drug activity of the finished botanicals, and continuous tracking of the metabolite markers of the disease;
    对植物药的临床实验进行追踪。Follow up the clinical trials of botanicals.
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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020081750A1 (en) * 2000-12-22 2002-06-27 Michael Ernest Drug evaluation operating principles
CN1875274A (en) * 2003-09-05 2006-12-06 荷兰应用科学研究会(Tno) Method for determining the impact of a multicomponent natural product mixture on the biological profile of a disease within a group of living systems and the development and quality control of natural
CN101299022A (en) * 2008-06-20 2008-11-05 河南中医学院 Method for evaluating Chinese medicine comprehensive quality using near infrared spectra technique
CN108593863A (en) * 2018-05-08 2018-09-28 南通市第二人民医院 A kind of online test method in extraction of traditional Chinese medicine and device
CN111180007A (en) * 2019-12-03 2020-05-19 深圳市开物成务中医药科技有限公司 Safe, effective and high-quality traditional Chinese medicine development platform system and implementation method

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101051041A (en) * 2006-04-06 2007-10-10 辛宁 Establishing method for Chinese medicine quantitative finger print atlas
CN102100706A (en) * 2009-12-18 2011-06-22 中国科学院大连化学物理研究所 Method for evaluating quality of Chinese patent medicament by using metabonomics
CN108152390A (en) * 2017-12-04 2018-06-12 武夷学院 A kind of roxburgh anoectochilus terminal bud HPLC fingerprint analysis methods
CN109270187B (en) * 2018-11-02 2022-05-10 江苏省中医院 Chinese medicine preparation quality evaluation method based on metabonomics and full-ingredient semi-quantitative analysis

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020081750A1 (en) * 2000-12-22 2002-06-27 Michael Ernest Drug evaluation operating principles
CN1875274A (en) * 2003-09-05 2006-12-06 荷兰应用科学研究会(Tno) Method for determining the impact of a multicomponent natural product mixture on the biological profile of a disease within a group of living systems and the development and quality control of natural
CN101299022A (en) * 2008-06-20 2008-11-05 河南中医学院 Method for evaluating Chinese medicine comprehensive quality using near infrared spectra technique
CN108593863A (en) * 2018-05-08 2018-09-28 南通市第二人民医院 A kind of online test method in extraction of traditional Chinese medicine and device
CN111180007A (en) * 2019-12-03 2020-05-19 深圳市开物成务中医药科技有限公司 Safe, effective and high-quality traditional Chinese medicine development platform system and implementation method

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