CN111180007A - Safe, effective and high-quality traditional Chinese medicine development platform system and implementation method - Google Patents
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Abstract
The invention relates to a safe, effective and high-quality traditional Chinese medicine development platform system and an implementation method thereof, wherein the platform system comprises: the system comprises a medicine quality monitoring unit for monitoring the quality of the plant medicine from a planting source, a multidimensional pharmacology unit for acquiring or discovering the active action data of the medicine, and a clinical curative effect unit for acquiring the clinical curative effect data. The system biology technology platform can establish a quality control system from a medicine source, and provides overall process quality management for the safety and the effectiveness of the botanical medicine; the effectiveness of the complex components of the botanical drug can be proved, and scientific basis is provided for the clinical application of the botanical drug; can determine the metabolite markers of the disease symptoms, and provide scientific diagnostic means for dialectical treatment of the plant medicine; the regulation and control relationship between the metabolite and different formulas can be proved, and basis is provided for the optimization of the plant medicine formula on the molecular level.
Description
Technical Field
The invention relates to the technical field of production and development of plant medicines, in particular to a safe, effective and high-quality traditional Chinese medicine development platform system and an implementation method.
Background
The botanical drug is a medicine for medical purposes which is a part or the whole of the plant and is divided into a traditional botanical drug and a modern botanical drug, and the plant extract produced by applying the modern scientific technology is the modern botanical drug; botanical drugs can be divided into: the whole (crude) extract-effective part-effective component (active combination) -effective component is divided into four layers, each layer has the possibility of developing into medicine; western medicine is used to refer to botanical drugs as natural drugs, and the botanical drug PRODUCTS defined by the European Union are not only single medicinal plants, but also various botanical drug combinations (herb medicine PRODUCTS), which contain specific plant active ingredients or plant extracts, and are used as MEDICAL PRODUCTS for MEDICAL purposes.
Current botanical drug production and development does not have a systematic platform to enable the association of botanical drug effectiveness, safety and quality control.
Disclosure of Invention
The technical problem to be solved by the present invention is to provide a safe, effective and high-quality platform system for developing traditional Chinese medicine and a method for implementing the same.
The technical scheme adopted by the invention for solving the technical problems is as follows:
a safe, effective and high-quality traditional Chinese medicine development platform system is constructed, wherein the system comprises a medicine quality monitoring unit for monitoring the quality of the plant medicine from a planting source, a multi-dimensional pharmacology unit for acquiring or discovering the active action data of the medicine, and a clinical curative effect unit for acquiring the clinical curative effect data.
The safe, effective and high-quality traditional Chinese medicine development platform system comprises a medicine quality monitoring unit and a plant variety database. The plant variety database is used for identifying and identifying each plant component for preparing the botanical drug.
The safe, effective and high-quality traditional Chinese medicine development platform system comprises a medicine quality monitoring unit and a medicine quality monitoring unit, wherein the medicine quality monitoring unit comprises an extract and mixture database, and the extract and mixture database is used for identifying and identifying extracts of plant components and mixtures of the extracts for manufacturing the plant medicines.
The safe, effective and high-quality traditional Chinese medicine development platform system comprises a medicine quality monitoring unit, wherein the quality analysis method of the plant medicine by the medicine quality monitoring unit comprises fingerprint spectrum and/or statistics.
The safe, effective and high-quality traditional Chinese medicine development platform system comprises a multi-dimensional pharmacological unit and a multi-element analysis unit, wherein the multi-element analysis unit is used for determining the influence of a multi-component plant medicine mixture on the biological characteristics of diseases in a group of life systems.
The safe, effective and high-quality traditional Chinese medicine development platform system comprises a multivariate analysis unit, wherein the multivariate analysis unit adopts the following method in measurement:
(a) comparing the biological characteristics of a group of living systems having disease symptoms with the biological characteristics of a group of control or healthy living systems to determine the biological characteristics of the disease;
(b) determining the effect of a series of samples of the multi-component mixture on a biological characteristic of the disease using multivariate analysis, wherein the samples differ in the concentration of one or more natural components or one or more groups of natural components;
(c) determining the expected effect of the composition of the multi-component mixture sample shown in step (b) on the biological characteristics of the disease using multivariate analysis;
(d) using multivariate analysis to determine in step (c) the effective natural components or groups of natural components and their respective concentrations required to produce the desired effect on the biological characteristics of the disease.
The safe, effective and high-quality traditional Chinese medicine development platform system further comprises a method for measuring by the multivariate analysis unit, wherein the method comprises the following steps:
(e) preparing one or more sets of natural product mixtures based on the information obtained in step (d), predicting the expected effect these mixtures will have on the biological characteristics of the disease;
(f) determining the effect of the multicomponent mixture prepared in step (e) on the biological properties of the disease.
The safe, effective and high-quality traditional Chinese medicine development platform system comprises a multi-dimensional pharmacological unit and a biomarker tracking unit, wherein the biomarker tracking unit is used for continuously tracking the metabolite markers of symptoms and feeding back the marker states.
The safe, effective and high-quality traditional Chinese medicine development platform system is characterized in that the clinical curative effect unit is communicated with an external clinical test mechanism to obtain clinical test data of the clinical test mechanism aiming at the botanical medicine.
A safe, effective and high-quality traditional Chinese medicine development platform system implementation method comprises the following steps:
quality supervision is carried out on the characteristics of the plant components, the plant component extracts and the mixture of the extracts in the preparation of the plant medicine;
performing multiplex analysis on the medicinal activity of the prepared botanical drug, and continuously tracking the metabolite markers of the disease symptoms;
clinical trials of botanical drugs were followed.
The invention has the beneficial effects that: the system biology technology platform can establish a quality control system from a medicine source, and provides overall process quality control for the safety and the effectiveness of the botanical medicine; the effectiveness of the complex components of the botanical drug can be proved, and scientific basis is provided for the botanical drug; can determine the metabolite markers of the disease symptoms, and provide scientific diagnostic means for dialectical treatment of the plant medicine; the regulation and control relationship between the metabolite and different formulas can be proved, and basis is provided for the optimization of the plant medicine formula on the molecular level.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions based on the prior art, the present invention will be further described with reference to the accompanying drawings and embodiments. The following figures are only some embodiments of the invention, from which a person skilled in the art will appreciate that further gains can be obtained.
FIG. 1 is a schematic block diagram of a safe, effective, high-quality Chinese medicine development platform system according to an embodiment of the present invention;
FIG. 2. finding multi-factor intervention programs by systemic drug response fingerprinting (left) and comparing (right) and correlating with disease system biomarkers to find new biomarkers and therapeutic targets;
FIG. 3 is a systemic response map of a drug in an animal model of chronic disease;
FIG. 4. disease biomarker associated network measured by systemic biology experiments: the basis of the intervention design of the combined medicament.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the embodiments of the present invention will be described in detail and fully hereinafter with reference to the accompanying drawings. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without any inventive work belong to the protection scope of the present invention.
The safe, effective and high-quality traditional Chinese medicine development platform system of the embodiment of the invention is shown in figure 1 and comprises a medicine quality monitoring unit 1 for monitoring the quality of the plant medicine from a planting source, a multi-dimensional pharmacology unit 2 for acquiring or discovering the active action data of the medicine and a clinical curative effect unit 3 for acquiring the clinical curative effect data. The system biology technology platform can establish a quality control system managed from a medicine source, and provides process quality control for the safety and the effectiveness of the botanical medicine; the effectiveness of the complex components of the botanical drug can be proved, and scientific basis is provided for the botanical drug; can determine the metabolite markers of the disease symptoms, and provide scientific diagnostic means for dialectical treatment of the plant medicine; the regulation and control relationship between the metabolite and different formulas can be proved, and basis is provided for the optimization of the plant medicine formula on the molecular level.
By adopting the technical scheme of the invention, the development and quality control of the plant-based medicine can be realized.
Preferably, the drug quality monitoring unit comprises a plant species database. The plant variety database is used for identifying and identifying each plant component for preparing the botanical drug;
the plant components can be acquired offline and uploaded according to the shapes, the smells, the colors and the like of the plant components, and the attributes of the plant components such as the authenticity, the quality grade and the like are verified by comparing the plant variety database data of the platform so as to ensure the reliable quality of the plant components.
Preferably, the drug quality monitoring unit comprises an extract and mixture database, and the extract and mixture database is used for identifying and identifying each plant component extract and each mixture of extracts for preparing the plant drug.
The method can acquire data such as color, transparency, sedimentation state and the like of the extracts of single plant components or the mixtures of multi-component extracts on line and upload the data, and performs data comparison by depending on the extracts of the platform and the mixture database so as to ensure the reliable quality of the extracts of the plant components and the mixtures of the extracts.
Preferably, the quality analysis method of the plant medicine by the medicine quality monitoring unit comprises fingerprint spectrum and/or statistics.
Preferably, the multi-dimensional pharmacological unit comprises a multivariate analysis unit. The multivariate analysis unit is used to determine the effect of a multi-component botanical drug mixture on the biological characteristics of a disease within a group of living systems.
Preferably, the method used for the measurement by the multivariate analysis unit is as follows:
(a) comparing the biological characteristics of a group of living systems with disease symptoms to the biological characteristics of a reference or healthy group of living systems to determine the biological characteristics of the disease;
(b) determining the effect of a series of samples of the multi-component mixture on a biological characteristic of the disease using multivariate analysis, wherein the samples differ in the concentration of one or more natural components or one or more groups of natural components;
(c) determining the expected effect of the composition of the multi-component mixture sample shown in step (b) on the biological characteristics of the disease using multivariate analysis;
(d) using multivariate analysis to determine in step (c) the effective natural components or groups of natural components and their respective concentrations required to produce the desired effect on the biological characteristics of the disease.
Preferably, the method for measuring by the multivariate analysis unit further comprises:
(e) preparing one or more sets of natural product mixtures based on the information obtained in step (d), predicting the expected effect these mixtures will have on the biological characteristics of the disease;
(f) determining the effect of the multicomponent mixture prepared in step (e) on the biological properties of the disease.
By adopting the technical scheme of the invention, the multi-component plant medicine mixture can be developed within a specified quality range. The quality of individual natural components or groups of natural components may differ locally due to different culture conditions. If one or more of the natural components or one or more of the groups of natural components do not have the desired quality, the multi-component mixture can be adjusted to one or more of the natural components or groups of natural components to achieve the desired effect on the biological characteristics of the disease.
For example, it may be determined by adjusting the amount of the corresponding natural component or components or groups of natural components to obtain the desired concentration of the natural component or components or groups of natural components to ensure that the multicomponent mixture will have the desired effect on the biological characteristics of the disease.
A multi-component botanical drug mixture is a botanical drug component or mixture of botanical drug components that is not produced by chemical synthesis but by a natural process. For example, a multi-component herbal mixture will contain two or more herbs, which may contain many different ingredients.
The method can measure the intervention effect of multiple targets in a unique way, and perform the intervention in an optimal way to reveal the biological characteristics of the effective components. In addition to the effects of simple disturbances such as single drugs, complex disturbances using multicomponent mixtures can be revealed. Such as herbal products and functional foods. This unique approach, known as multidimensional pharmacology (MDP), uses systems biology to study biological systems by measuring and integrating metabolic data and other aspects of the data (e.g., genetic and/or proteomic data).
The above methods are not limited to merely measuring biological and synergistic effects in mammalian systems, but can also address all possible forms of biological systems, including complex compounds from the same life combination.
In health and disease studies, the fluid body characteristics of plasma samples from a control group (reference group) and a patient group (disease symptom group with biological characteristics) can be used to measure as many components as possible and to assess the differences in single components or component patterns between the two groups in order to better understand the underlying biological mechanisms, detect new biomarkers/surrogate markers, predict toxicological or pharmacological responses or develop new intervention pathways.
The biological characteristics to be determined in step (a) preferably include one or more metabolic, gene expression and/or protein characteristics, although combinations of these characteristics may also be used.
In step (a), the biological characteristics of at least one body fluid or at least one tissue are preferentially determined.
Determining in step (a) a biological characteristic using one or more of the following biomarkers: genes, transcripts, proteins, metabolites and (trace) elements.
In step (b), the influence of a series of samples of the multi-component mixture on the biological characteristics of the disease is preferentially determined using at least one spectrometric technique, at least one electronic transition-based technique or at least one chromatographic technique.
In step (c), the composition of the sample is preferably determined using at least one spectrometric technique, at least one electron-based transition technique or at least one chromatographic technique.
In step (d), preferably at least one spectrometric technique, at least one electron transition based technique or at least one chromatographic technique is used to identify the active component or group of components and their respective concentrations required to exert an effect on the organism.
In step (f), preferably at least one spectrometric technique, at least one electron transition-based technique or at least one chromatographic technique is used to identify the active component or group of components and their respective concentrations required to exert an effect on the organism.
The multi-component mixture used in the present invention may be any multi-component mixture having (potential) influence on the biological characteristics of the disease. The multicomponent mixture may be any botanical drug.
Preferably, in each of steps (a) - (d) and (f) (e), at least one spectrometric technique is used. Nuclear magnetic resonance ("NMR") or mass spectrometry ("MS") techniques can be suitably used, 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.
Preferably at least nuclear magnetic resonance and/or mass spectrometry techniques are used in each of steps (a) - (d) and (f) (e), mass spectrometry techniques being preferred in the field of protein analysis (proteomics).
In the case of small molecules, sample preparation for nmr can usually be very simple to use freeze drying and reconstitution in D2O, since the emphasis is on high concentrations of the components, i.e. 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.
In each of steps (a) - (d) and (f) (e), spectroscopic data obtained from one or more platforms can be used, including, but not limited to, mass spectrometry techniques, nuclear magnetic resonance techniques, liquid chromatography ("LC"), gas chromatography ("GC"), high performance liquid chromatography ("HPLC"), capillary electrophoresis ("CE"), and any known form of coupled mass spectrometry in low or high resolution mode, such as LC-MS, GC-MS, CE-MS, LC-UV, MS-MS, MSn, and the like. Typical data can also be obtained by using more component specific detectors, such as laser induced fluorescence and electrochemical detection.
As used herein, the term "spectroscopic data" includes data from any spectrometric or chromatographic technique. Spectroscopic techniques include, but are not limited to, nuclear magnetic resonance spectroscopy, infrared spectroscopy, raman spectroscopy, and ultraviolet spectroscopy, among others mass spectroscopy. Chromatographic techniques include, but are not limited to, liquid chromatography, gas chromatography, and electrophoresis.
Preferably, the multidimensional pharmacological unit comprises a biomarker tracking unit for continuously tracking the metabolite markers of the condition and feeding back the marker status;
in the context of the present application, biomarkers are defined as features that are objectively measured and evaluated: normal biological processes, pathogenic processes, or pharmacological responses to therapeutic intervention.
The biomarker may be a gene, transcript, protein, metabolite (trace element) or any combination of these components.
Preferably, the clinical curative effect unit is in contact with an external clinical test mechanism, and clinical test data of the clinical test mechanism aiming at the botanical drug are acquired.
A plant-to-patient system biology method is realized according to the safe, effective and high-quality traditional Chinese medicine development platform system, and comprises the following steps:
quality supervision is carried out on the characteristics of the plant components, the plant component extracts and the mixture of the extracts in the preparation of the plant medicine;
performing multiplex analysis on the medicinal activity of the prepared botanical drug, and continuously tracking the metabolite markers of the disease symptoms;
tracking clinical experiments of the botanical drug;
the system biology technology platform can establish a quality control system from a medicine source, and provides whole-process quality management for the safety and the effectiveness of the botanical medicine; the effectiveness of the complex components of the botanical drug can be proved, and scientific basis is provided for the botanical drug; can determine the metabolite markers of the disease symptoms, and provide scientific diagnostic means for dialectical treatment of the plant medicine; the regulation and control relationship between the metabolite and different formulas can be proved, and basis is provided for the optimization of the plant medicine formula on the molecular level.
It will be understood that modifications and variations can be made by persons skilled in the art in light of the above teachings and all such modifications and variations are intended to fall within the scope of the appended claims.
Claims (10)
1. A safe, effective and high-quality traditional Chinese medicine development platform system is characterized by comprising: the system comprises a medicine quality monitoring unit for monitoring the quality of the plant medicine from a planting source, a multidimensional pharmacology unit for acquiring or discovering the active action data of the medicine, and a clinical curative effect unit for acquiring the clinical curative effect data.
2. The safe, effective and high quality platform system for development of chinese traditional medicine according to claim 1, wherein said drug quality monitoring unit comprises: and the plant variety database is used for identifying and identifying each plant component for preparing the botanical drug.
3. The safe, effective and high quality platform system for development of chinese traditional medicine according to claim 1, wherein said drug quality monitoring unit comprises: and the extract and mixture database is used for identifying and identifying the extracts of the plant components and the mixtures of the extracts for preparing the plant medicines.
4. The platform system for safe, efficient and high quality herbal medicine development according to any one of claims 1 to 3, wherein the quality monitoring unit performs quality analysis of the herbal medicine by fingerprint and/or statistics.
5. The safe, effective, high quality chinese medicine development platform system of claim 1 wherein the multi-dimensional pharmacology unit comprises: a multivariate analysis unit for determining the effect of a multi-component botanical drug mixture on the biological characteristics of a disease within a group of living systems.
6. The safe, effective and high-quality platform system for developing Chinese traditional medicine according to claim 5, wherein the multivariate analysis unit adopts the following method for determination:
(a) comparing the biological characteristics of a group of living systems having disease symptoms with the biological characteristics of a group of control or healthy living systems to determine the biological characteristics of the disease;
(b) determining the effect of a series of samples of the multi-component mixture on a biological characteristic of the disease using multivariate analysis, wherein the samples differ in the concentration of one or more natural components or one or more groups of natural components;
(c) determining the expected effect of the composition of the multi-component mixture sample shown in step (b) on the biological characteristics of the disease using multivariate analysis;
(d) using multivariate analysis to determine in step (c) the effective natural components or groups of natural components and their respective concentrations required to produce the desired effect on the biological characteristics of the disease.
7. The safe, effective and high-quality platform system for developing chinese traditional medicine according to claim 6, wherein the multivariate analysis unit further comprises, when performing the determination, the method of:
(e) preparing one or more sets of natural product mixtures based on the information obtained in step (d), predicting the expected effect these mixtures will have on the biological characteristics of the disease;
(f) determining the effect of the multicomponent mixture prepared in step (e) on the biological properties of the disease.
8. A safe, effective, high quality platform system for development of chinese traditional medicines according to claim 1, wherein the multi-dimensional pharmacology unit comprises a biomarker tracking unit for continuous tracking of metabolic markers of disorders and feedback of marker status.
9. The safe, effective and high-quality platform system for developing Chinese herbal medicines according to claim 1, wherein the clinical efficacy unit is in communication with an external clinical trial institution, and clinical trial data for the botanical drugs are acquired by the clinical trial institution.
10. A method for implementing a safe, efficient and high-quality platform system for developing chinese traditional medicine, according to any one of claims 1 to 9, characterized in that the method comprises:
quality supervision is carried out on the characteristics of the plant components, the plant component extracts and the mixture of the extracts in the preparation of the plant medicine;
performing multiplex analysis on the medicinal activity of the prepared botanical drug, and continuously tracking the metabolite markers of the disease symptoms;
clinical trials of botanical drugs were followed.
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| WO2021109923A1 (en) * | 2019-12-03 | 2021-06-10 | 深圳市开物成务中医药科技有限公司 | Safe, effective and high-quality chinese medicine development platform system and realization method |
Citations (6)
| 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 effect of multicomponent natural product mixtures on the bioprofiling of diseases in a panel of living systems and for the development and quality control of natural product-based pharmaceuticals |
| 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 |
| CN109270187A (en) * | 2018-11-02 | 2019-01-25 | 江苏省中医院 | A kind of Chinese materia medica preparation quality evaluating method based on metabolism group Yu full ingredient semi-quantitative analysis |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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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Patent Citations (6)
| 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 effect of multicomponent natural product mixtures on the bioprofiling of diseases in a panel of living systems and for the development and quality control of natural product-based pharmaceuticals |
| 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 |
| CN109270187A (en) * | 2018-11-02 | 2019-01-25 | 江苏省中医院 | A kind of Chinese materia medica preparation quality evaluating method based on metabolism group Yu full ingredient semi-quantitative analysis |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021109923A1 (en) * | 2019-12-03 | 2021-06-10 | 深圳市开物成务中医药科技有限公司 | Safe, effective and high-quality chinese medicine development platform system and realization method |
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