CN103077322A - Cardiovascular toxicity evaluation predicting system and method of traditional medicine - Google Patents
Cardiovascular toxicity evaluation predicting system and method of traditional medicine Download PDFInfo
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Abstract
The invention provides a cardiovascular toxicity evaluation predicting system and a cardiovascular toxicity evaluation predicting method of traditional medicine. The system comprises a literature data evaluation sub-system, a chemical component toxicity evaluation sub-system, an animal experiment evaluation sub-system and a comprehensive evaluation module, wherein the comprehensive evaluation module is related to each sub-system. The method comprises the following steps of: searching cardiovascular toxicity literatures of the to-be measured traditional medicine, performing cardiovascular toxicity evaluation on the chemical components, performing cardiovascular toxicity evaluation on the to-be measured traditional medicine through an animal experiment, and combining the results to give a cardiovascular toxicity evaluation predicting result of the traditional medicine. By the method and the system, the toxicity of the traditional medicine can be rapidly and accurately evaluated, the toxicity risk of the traditional medicine can be exactly predicted in time, the large amount of funds and time are saved, and the toxic and side effect of the traditional medicine can be evaluated and improved.
Description
Technical field
The present invention relates to a kind of method of evaluation and forecast and system thereof of area of computer aided medicine, particularly be a kind of Cardiovascular Toxicity method of evaluation and forecast and system thereof of conventional medicament.
Background technology
Cardiovascular Toxicity is the important indicator that drug safety is estimated.Conventional medicament, such as Chinese medicine, Tibetan medicine etc., come from the materials such as natural animals and plants, mineral matter, often appear in the medicinal application with the compound form again, its chemical substance basis and the mechanism of action are very complicated, thereby the difficulty of its drug safety evaluation is very large, usually need to carry out comprehensive evaluation by a large amount of literature queries, zoopery, clinical trial etc.
The toxicity research of conventional medicament and evaluation and test at home and abroad all are weak links, to the toxicity assessment of conventional medicament, usually adopt a large amount of artificial and laboratory means, consume substantial contribution and time, become and hinder conventional medicament modernization and international important bottleneck.
The blocking effect and the effect of QT interval prolongation that studies show that hERG (the human ether-à-go-go related gene) potassium-channel of chemicals have close correlativity, easily cause torsades de pointes chamber speed and arrhythmia cordis.Therefore, early stage at drug development, generally by observing the arrhythogenic potential danger of lead compound is assessed in the impact of hEGR potassium channel, to evade the risk of medicine Cardiovascular Toxicity.The non-experimental Forecasting Methodology of existing compound hERG blocking effect, generally complicated such as neural network, support vector machine etc., and need to use specific business software, promotion and application are all relatively more difficult, can not satisfy the needs of medicament research and development.
The means of detection of drugs Cardiovascular Toxicity mainly are by zoopery at present, and such as mouse, rabbit, dog, monkey, zebra fish etc., but expensive, general survival dose is larger, can not realize that high pass quantizes; The cellular level experiment also can be used for the medicine Cardiovascular Toxicity and detects, and for example by the impact of patch clamp technique detection of drugs on hERG, but cellular level and clinical test results difference are larger, and accuracy leaves a question open.
Summary of the invention
The present invention is directed to the problems referred to above, provide a kind of rapidly to method and the system thereof of the Cardiovascular Toxicity evaluation of conventional medicament prediction, can be fast, accurately, economically the Cardiovascular Toxicity of conventional medicament is estimated prediction.
In order to realize above-mentioned task, the present invention takes following technical solution:
A first aspect of the present invention, provide a kind of conventional medicament Cardiovascular Toxicity to estimate prognoses system, described system comprises three sub-systems and comprehensive evaluation module: the data in literature Evaluation subsystem: described subsystem carries out the literature search analysis to conventional medicament to be measured and active drug composition thereof, filters out conventional medicament or effective constituent with Cardiovascular Toxicity report; Chemical constitution toxicity assessment subsystem: described subsystem, convert conventional medicament to be measured to the chemical composition data collection, the chemical constitution of medicine to be predicted is carried out the evaluation prediction of Cardiovascular Toxicity; The zoopery Evaluation subsystem: described zoopery Evaluation subsystem carries out zoopery to medicine to be predicted, draw the animal used as test data of conventional medicament Cardiovascular Toxicity prediction, set up the dose-effect relationship model, extrapolation obtains people's minimum safe metering, estimates accordingly the Cardiovascular Toxicity of medicine; The comprehensive evaluation module: by the comprehensive evaluation module result of described data in literature Evaluation subsystem, chemical constitution Evaluation subsystem, zoopery Evaluation subsystem is carried out comprehensive evaluation, the Cardiovascular Toxicity that draws described conventional medicament is estimated prediction conclusion; Described comprehensive evaluation module is associated with described each subsystem.
A second aspect of the present invention, a kind of Cardiovascular Toxicity method of evaluation and forecast of conventional medicament is provided, the step of described method comprises: step 1, conventional medicament to be measured and active drug composition thereof are carried out the literature search analysis, filter out the report that conventional medicament and effective chemical constitution thereof have Cardiovascular Toxicity; Step 2 converts conventional medicament to be measured to the chemical constitution set, for the chemical constitution of conventional medicament to be predicted, carries out one by one the evaluation prediction based on the Cardiovascular Toxicity of Chemoinformatics method; Step 3 is carried out zoopery to medicine to be predicted, draws the animal experimental data of conventional medicament Cardiovascular Toxicity prediction, sets up the dose-effect relationship model, and extrapolation obtains people's minimum safe metering, estimates accordingly the Cardiovascular Toxicity of medicine; Step 4, comprehensive above-mentioned steps predicts the outcome and carries out comprehensive evaluation, judges the Cardiovascular Toxicity of the described conventional medicament of prediction; Described step 1, step 2, step 3 are in no particular order.
A third aspect of the present invention, provide a kind of evaluation prognoses system of conventional medicament Cardiovascular Toxicity of utilizing to carry out the method that the conventional medicament Cardiovascular Toxicity is predicted, the concrete steps of described method comprise: (1) starts the conventional medicament Cardiovascular Toxicity and estimates prognoses system, newly-built system's runnable interface; (2) in input window, input a traditional medicine name, perhaps consist of a series of traditional medicine names of a prescription; (3) system judges according to backstage conventional medicament noun list whether the traditional medicine name of input is correct, if correctly then continue, otherwise returns step (2), revises the traditional medicine name of inputting; (4) the data in literature Evaluation subsystem carries out literature search according to the traditional medicine name of input, and produces the retrieval appraisal report; (5) chemical constitution toxicity assessment subsystem obtains the chemical constitution set of described conventional medicament according to the traditional medicine name of input, and to the analyzing cardiovascular toxicity one by one of the chemical constitution in this set, generates at last chemical constitution Cardiovascular Toxicity appraisal report; (6) the zoopery Evaluation subsystem is introduced experiment porch with medicine to be predicted, by in two or more zooperies, forms the Report on Animal of medicine to be predicted; (7) the comprehensive evaluation module gathers above-mentioned three parts of appraisal reports, forms the final evaluation prediction address to medicine to be predicted.
A fourth aspect of the present invention, a kind of method that the conventional medicament prescription is improved with the evaluation method of conventional medicament Cardiovascular Toxicity is provided, the step of described method is: step 1 draws the appraisal report for the treatment of improved conventional medicament prescription according to the evaluation method of conventional medicament Cardiovascular Toxicity; Step 2, result according to described appraisal report, for the larger chemical constitution of Cardiovascular Toxicity, find conventional medicament composition corresponding in the conventional medicament, adopt the similar conventional medicament composition of therapeutic action to replace the larger composition of described conventional medicament prescription central vessel toxicity.
Conventional medicament Cardiovascular Toxicity of the present invention is estimated prognoses system and method thereof, can predict in time, exactly grinding the Cardiovascular Toxicity risk of medicine in the early stage of drug development, saves a large amount of fund and time.Evaluation by method and system of the present invention, draw the definite result of the Cardiovascular Toxicity that this conventional medicament product exists, can be used as the bad reaction that has of this medicine of judgement and the reference of taboo, also can improve the impulse that plays for the conventional medicament prescription, improve by the prescription of method of the present invention to the conventional medicament product, reach the purpose that keeps drug effect when reducing cardiovascular toxic and side effect.The framework of system of the present invention has good dirigibility and extensibility, can be applied to easily in the prediction to chemicals other biological activity.
Description of drawings
Fig. 1 is framework and the principle schematic that a kind of conventional medicament Cardiovascular Toxicity of the present invention is estimated prognoses system.
Fig. 2 is that a kind of conventional medicament Cardiovascular Toxicity of the present invention is estimated in the prognoses system framework and the workflow synoptic diagram of preferred conventional medicament bibliographic data base Evaluation subsystem.
Fig. 3 is that a kind of conventional medicament Cardiovascular Toxicity of the present invention is estimated in the prognoses system framework and the workflow synoptic diagram of preferred chemical constitution Evaluation subsystem.
Fig. 4 is that a kind of conventional medicament Cardiovascular Toxicity of the present invention is estimated in the prognoses system framework and the workflow synoptic diagram of preferred zoopery Evaluation subsystem.
Fig. 5 is a kind of conventional medicament Cardiovascular Toxicity method of evaluation and forecast and system according to the present invention, " the internationalization of tcm Cardiovascular Toxicity is estimated integrated information system " surface chart of foundation.
Description of reference numerals
10 conventional medicaments to be predicted
110 data in literature Evaluation subsystems
111 load modules, 112 data processing modules, 113 conventional medicament natural products databases, 114 scientific and technological literature database 115FDA drug data bases, 116 world's conventional medicament patent databases
117 pharmaceutical control and administration rules databases, 118 literature search analysis reports
120 chemical constitution toxicity assessment subsystems
121 pharmaceutical chemistry compositions, 122 compound Cardiovascular Toxicity prediction module, 123 compound hERG blocking effect prediction module 124 predict the outcome and gather submodule 125 pharmaceutical chemistry composition Cardiovascular Toxicity prediction addresses
130 zoopery Evaluation subsystems
131 zoopery platforms, 1311 guinea pig models, 1312 New Zealand white rabbit models, 1312 beasle dog models
135 dose-effect relationship modules, 136 animal experimental data storehouses, 137 Report on Animals
140 comprehensive evaluation modules
20 medicine Cardiovascular Toxicity predict the outcome
30 computer platforms
Embodiment
Below cooperate accompanying drawing, describe the embodiment of the present invention's a kind of conventional medicament Cardiovascular Toxicity method of evaluation and forecast and system in detail.
Embodiment one
Embodiment one provides a kind of evaluating system and method thereof of conventional medicament Cardiovascular Toxicity.
Specifically describe for System and method for of the present invention below in conjunction with accompanying drawing 1-4
Fig. 1 is framework and the principle schematic that a kind of conventional medicament Cardiovascular Toxicity of the present invention is estimated prognoses system.1 give following explanation for system of the present invention by reference to the accompanying drawings.
A kind of conventional medicament Cardiovascular Toxicity of the present invention is estimated prognoses system, be comprised of three sub-systems and comprehensive evaluation module 140, described three sub-systems are: data in literature Evaluation subsystem 110, pharmaceutical chemistry composition toxicity assessment subsystem 120, zoopery Evaluation subsystem 130.Described comprehensive evaluation module 140 is associated with described each subsystem.
Particularly, described conventional medicament data in literature Evaluation subsystem 110 is used for conventional medicament to be measured and active drug composition thereof are carried out the literature search analysis, filters out conventional medicament and effective constituent with Cardiovascular Toxicity report; Described chemical constitution toxicity assessment subsystem 120 is used for converting conventional medicament to be measured to the chemical composition data set, the chemical constitution of medicine to be predicted is carried out the evaluation prediction of Cardiovascular Toxicity; Described zoopery Evaluation subsystem 130 is used for medicine to be predicted is carried out zoopery, draw the animal used as test data of conventional medicament Cardiovascular Toxicity prediction, set up the dose-effect relationship model, extrapolation obtains people's minimum safe metering, estimates accordingly the Cardiovascular Toxicity of medicine; Described comprehensive evaluation module 140 is used for the evaluation result of described conventional medicament data in literature Evaluation subsystem 110, chemicals composition Evaluation subsystem 120 and described zoopery Evaluation subsystem 130 is comprehensively judged that the Cardiovascular Toxicity that draws described conventional medicament is estimated prediction conclusion.
Conventional medicament to be measured is through the respectively evaluation of data in literature Evaluation subsystem 110, chemical constitution toxicity assessment subsystem 120, zoopery Evaluation subsystem 130 3 sub-systems, by the comprehensive evaluation module 140 that is associated with described each subsystem, the evaluation result that draws respectively for each subsystem gives comprehensive evaluation, provides comprehensive conventional medicament Cardiovascular Toxicity evaluation result.
As shown in Figure 2, be that a kind of conventional medicament Cardiovascular Toxicity of the present invention is estimated in the prognoses system framework of a preferred bibliographic data base Evaluation subsystem and workflow synoptic diagram.Be further described in more detail for conventional medicament data in literature Evaluation subsystem 110 below in conjunction with accompanying drawing 2.
As shown in Figure 2, the framework of data in literature Evaluation subsystem 110 of the present invention comprises: load module 111, data processing module 112, and conventional medicament database.Described conventional medicament database comprises a plurality of data word banks: conventional medicament natural products database 113, scientific and technological literature database 114, FDA drug data base 115, world's conventional medicament patent database 116, more than 117 data word bank of pharmaceutical control and administration rules database.
Wherein, data processing module 112 is set up active data and is connected between load module 111 and each data word bank, be the corn module of system.By the synergy of load module 111, data processing module 112 and conventional medicament database, finish the work such as typing, data retrieval, information processing, evaluation result output of conventional medicament information.Described load module 111 is used for finishing input and the analysis of conventional medicament to be predicted and conventional medicament prescription, and response user's various operations, described load module 111 also comprises: conventional medicament noun list, be used for storing rectification of name, another name and the database login number of every kind of conventional medicament, data to input are carried out real-time analysis, the traditional medicine name of user's input is converted into the accession number sequence, is used for the retrieval in later stage; Traditional medicine name prompting submodule is used for the data according to above-mentioned conventional medicament noun list, provides real-time prompting in the user inputs the process of traditional medicine name, to raise the efficiency, to reduce mistake, preferably, provides real-time prompting with the form of drop-down list.
In the described conventional medicament database, described conventional medicament natural products database 113 is for structure and the biologically active data of store and management conventional medicament natural products; Described scientific and technological literature database 114 is used for the store and management Chinese and English scientific and technical literature data relevant with drug toxicity; Described FDA drug data base 115 is used for all drug study data that store and management FDA reports; Described pharmaceutical control and administration rules database 117 is used for the store and management countries in the world pharmaceutical control and administration rules relevant with drug toxicity; Described world conventional medicament patent database 116 is used for store and management and worldwide conventional medicament patent; Described data processing module 112 is used for finishing the analysis of conventional medicament to be predicted and conventional medicament prescription, and response user's various operations.
Fig. 3 is that a kind of conventional medicament Cardiovascular Toxicity of the present invention is estimated in the prognoses system framework of a preferred chemicals composition Evaluation subsystem and workflow synoptic diagram.Be further described in more detail for chemicals composition Evaluation subsystem below in conjunction with accompanying drawing 3.
In the preferred embodiment as shown in Figure 3, described chemical constitution toxicity assessment subsystem 120 comprises: compound Cardiovascular Toxicity prediction module 122, compound hEGR blocking effect prediction module 123 predicts the outcome and gathers submodule 124.Preferably, conventional medicament 10 to be predicted is by the chemical constitution 121 of conventional medicament natural products database 113 these conventional medicaments of generation on backstage, and generally, described chemical constitution enters prediction flow process afterwards with the form of chemical composition data set.
Comprise the Cardiovascular Toxicity compound library in the described compound Cardiovascular Toxicity prediction module 122, described Cardiovascular Toxicity compound library has been collected all known Cardiovascular Toxicity compound data, is used for realizing the compound Cardiovascular Toxicity evaluation of conventional medicament chemical constitution.Preferably, the evaluation of the compound Cardiovascular Toxicity test and appraisal module in the described chemical toxicity composition Evaluation subsystem 120 is to estimate by the algorithm of molecular structure similarity.
Studies show that, if the chemical constitution of conventional medicament blocking-up hERG (human ether-à-go-go related gene) potassium-channel then causes torsades de pointes chamber speed and arrhythmia cordis easily, produce Cardiovascular Toxicity.Therefore, by estimating prediction for chemical constitution hERG potassium-channel blocking effect, can realize the evaluation for the Cardiovascular Toxicity of conventional medicament.
In chemical constitution toxicity assessment subsystem of the present invention, comprise Cardiovascular Toxicity molecular characterization storehouse in the described compound hEGR blocking effect prediction module 123, be used for the molecular structure fragment relevant with hERG potassium-channel blocking effect that storage has been reported, be used for realizing the evaluation of compound hERG blocking effect.Preferably, the evaluation of described compound hERG blocking effect prediction module is to estimate by chemical feature Structure Identification algorithm.Its theoretical foundation is that the bioactive dominance structure of compound is theoretical, and the compound that namely has some certain structural features can produce specific biologically active usually.
A preferred scheme is that described molecular characterization storehouse comprises: the property estimated feature database, low activity feature database and high activity feature database.
The described property estimated feature database, be used for the storage known molecular architectural feature relevant with the property estimated, cause the chemicals of evaluation result high error rate to be got rid of to meeting, if the molecular structure of compound to be tested and assessed comprises the architectural feature in this storehouse, judge that then this molecule is not suitable for using native system to test and assess, system will stop follow-up test and appraisal work.The known chemical molecular architectural feature that should get rid of comprises: macrocyclic antibiotic, polypeptide, bridged ring micromolecular, mineral compound and molecular weight are greater than 800 medicine.
Described low activity feature database is used for the storage molecular characterization relevant with low activity.Described low activity feature, refer to the molecular characterization of the known reduction hERG blocking effect that has, if the molecular structure of compound to be tested and assessed comprises one or more architectural features in this storehouse, judge that then this molecule has the hERG of reduction blocking-up activity, system will stop follow-up test and appraisal work, provide evaluating result.Low hERG blocking-up active structure feature includes but not limited to following several: carboxyl, azido, alkynyl.
Described high activity feature database is used for the storage known molecular architectural feature relevant with high activity.Described high activity feature, refer to the known molecular characterization with hERG blocking effect, if the molecular structure of compound to be tested and assessed comprises one or more architectural features in this storehouse, judge that then this molecule has high hERG blocking-up activity, system provides evaluating result.High hERG blocking-up active structure feature includes but not limited to: phenyl ethylamine, amphetamine etc. also comprise following characterization of molecules structure:
Above-mentioned feature structure is a minor structure, is present in the organic molecule; Link to each other by 5 chemical bonds between phenyl ring and the terminal N atom, wherein chemical bond can be singly-bound, two key, triple bond, aromatic gp; Wherein said feature structure can not form a closed-loop construct by other atoms or chemical bond connection.
By the molecular characterization storehouse that the property estimated feature database, low activity feature database and high activity feature database form, be used for the molecular structure fragment that respectively storage has above-mentioned certain sense, especially have the architectural feature of above-mentioned particular biological meaning.The physical store form in described molecular characterization storehouse comprises: data file, database; The logical storage mode of molecular characterization in the storehouse includes but not limited to following several: each molecular characterization is stored as separately a file, a plurality of molecular characterization is stored as a file, passes through the database storage administration; Each molecular characterization is stored with the chemical code form, and coded format includes but not limited to following several: mol file, mol2 file, sdf file, smiles code, inchi code.The molecular characterization that store in the molecular characterization storehouse can be the molecular structure fragment of determining, also can be simple family's property structure.
The chemistry core algorithm of the employing in the described compound Cardiovascular Toxicity prediction module 122 is preferably chemical molecular structural similarity algorithm, can estimate for the Cardiovascular Toxicity quantitative of conventional medicament; The core algorithm of the chemistry that adopts in the described compound hEGR blocking effect prediction module 123 is preferably chemical feature Structure Identification algorithm, can provide qualitative evaluation for the Cardiovascular Toxicity of conventional medicament.These two modules are treated the Cardiovascular Toxicity evaluation result that predictive compound provides multi-angle based on different theoretical, have guaranteed the accuracy of evaluation result.Can select above-mentioned two prediction module simultaneously conventional medicament 10 to be measured to be carried out the chemical constitution toxicity assessment, also can select separately one of above-mentioned two prediction module that conventional medicament 10 to be measured is carried out the chemical constitution toxicity assessment.
By inputting conventional medicament information to be measured, convert conventional medicament to be predicted to chemical constitution 121, be generally the chemical composition data set, by described compound Cardiovascular Toxicity prediction module 122 and/or compound hEGR blocking effect prediction module 123 generation forecast results, gather the chemical constitution Cardiovascular Toxicity appraisal report that submodule 124 provides conventional medicament by described predicting the outcome at last afterwards.
Preferably, described predicting the outcome gathered submodule 124 and also comprised: the molecular structure of compounds display sub-module is used for providing at prediction address and the navigation process that predicts the outcome the molecular structure Presentation Function of compound.
Fig. 4 is that a kind of conventional medicament Cardiovascular Toxicity of the present invention is estimated in the prognoses system framework of a preferred zoopery Evaluation subsystem and workflow synoptic diagram.Be further described in more detail for zoopery Evaluation subsystem 130 below in conjunction with accompanying drawing 4.
As shown in Figure 4, described zoopery Evaluation subsystem 130 comprises: zoopery platform 131, dose-effect relationship module 135, animal experimental data storehouse 136.Described zoopery platform comprises a plurality of animal models, as shown in Figure 4 be preferred animal model: guinea pig model 1311, New Zealand white rabbit model 1312,1,313 three kinds of animal models of beasle dog model.Conventional medicament to be predicted is with extract or medicinal extract form, test at zoopery platform 131, on the animal used as test more than two kinds, all obtain the experimental data of QT interval prolongation, in this data storage and the animal experimental data storehouse, set up the various amount effect relation curve of many animals by described dose-effect relationship module, calculate comparable maximum safe dose, obtain people's maximum safe dose by this dosage extrapolation, gather above data, described conventional medicament is activated thing QT interval prolongation carry out risk assessment, form Report on Animal 137.
The comprehensive evaluation module: by the comprehensive evaluation module result of described conventional medicament data in literature Evaluation subsystem, chemicals composition Evaluation subsystem and described zoopery Evaluation subsystem is carried out comprehensive evaluation, the Cardiovascular Toxicity that draws described conventional medicament is estimated prediction conclusion.
As shown in Figure 1, described comprehensive evaluation data module 140, the evaluation of described literature search evaluation result, chemicals composition Evaluation subsystem predicted the outcome compare with predicting the outcome of described zoopery Evaluation subsystem, judge the described conventional medicament of prediction Cardiovascular Toxicity carry out analysis-by-synthesis, provide final evaluation and predict the outcome, and response user's various operations.
Preferably, described comprehensive evaluation module comprises at least: load module, for the evaluation result of input data in literature Evaluation subsystem, chemical constitution toxicity assessment subsystem, zoopery Evaluation subsystem; The comprehensive evaluation data processing module, for the qualitative analysis of the Cardiovascular Toxicity of finishing conventional medicament to be predicted, and response user's various operations.
Preferably, described each subsystem is related with computer platform with the comprehensive evaluation module, described data in literature Evaluation subsystem, chemical constitution toxicity assessment subsystem, zoopery Evaluation subsystem are mutually independent, in native system, can be according to user's needs, select neatly one or more Evaluation subsystems to estimate for conventional medicament Cardiovascular Toxicity to be predicted, draw corresponding evaluation conclusion.
Embodiment two
The evaluating method of a kind of conventional medicament Cardiovascular Toxicity provided by the invention, below in conjunction with accompanying drawing 1-4, shown system and principle are described the evaluating method of a kind of conventional medicament Cardiovascular Toxicity of the present invention.
The evaluating method of conventional medicament Cardiovascular Toxicity of the present invention comprises the steps:
Step 1 is carried out the literature search analysis to conventional medicament to be measured and active drug composition thereof, filter out conventional medicament and effectively chemical constitution have a Cardiovascular Toxicity report; Step 2 converts conventional medicament to be measured to the chemical constitution set, for the chemical constitution of medicine to be predicted, carries out the evaluation prediction of Cardiovascular Toxicity; Step 3 is carried out zoopery to medicine to be predicted, draws the animal used as test data of conventional medicament Cardiovascular Toxicity prediction, sets up the dose-effect relationship model, and extrapolation obtains people's minimum safe metering, estimates accordingly the Cardiovascular Toxicity of medicine; Step 4, the result of comprehensive above-mentioned steps carries out comprehensive evaluation, provides the Cardiovascular Toxicity evaluation result of stating conventional medicament; Wherein said step 1, step 2, step 3 are in no particular order.
In the method for the invention, preferably, step 1, step 2, step 3 are separate, can independent assortment, for example, step 1, step 2 combination can be estimated prediction, and also can with step 2, step 3 combination, estimate prediction.
In the method for the invention, preferably, the evaluation of the described Cardiovascular Toxicity of step 2 prediction is quantitative, the qualitative evaluation prediction for the Cardiovascular Toxicity of conventional medicament to be measured.Preferably described evaluation prediction adopts the method for Chemoinformatics to carry out.A preferred scheme is, by conventional medicament to be measured is changed into the chemical constitution collection, the chemical constitution of conventional medicament to be predicted and the known chemical constitution with Cardiovascular Toxicity are carried out the chemical molecular structural similarity relatively and the chemical feature Structure Identification, accordingly chemicals is carried out the evaluation prediction of Cardiovascular Toxicity.
A preferred scheme is, by conventional medicament to be measured is changed into the chemical constitution collection, one by one the molecular structure of its chemical constitution and the known chemical constitution molecular structure with Cardiovascular Toxicity are carried out similarity relatively, judge the similarity of its molecular structure, draw the probability that described conventional medicament to be measured has Cardiovascular Toxicity, provide evaluation and predict the outcome.Described structural similarity comparative optimization adopts chemical molecular structural similarity algorithm.
Preferably, carry out the feature structure of hERG potassium-channel blocking effect by the compound for the treatment of test and appraisal and carry out identification, judge whether the compound that conventional medicament comprises has the hERG blocking effect, thereby realize compound hERG potassium-channel blocking effect is estimated prediction.Particularly, be to judge by the identification whether the chemical feature structure for the chemical constitution of conventional medicament to be measured has a known blocking-up hERG potassium-channel molecular characterization, qualitatively judge compound and whether have the Cardiovascular Toxicity effect.Chemical feature Structure Identification algorithm is preferably adopted in described architectural feature identification.
In step 4 of the present invention, combine step 1 of the present invention, step 2, step 3 adopt respectively that the distinct methods step draws the evaluation result for the Cardiovascular Toxicity of conventional medicament to be measured, comprehensive multiple angles evaluation predicts the outcome, draw final conclusion, therefore, described conventional medicament Cardiovascular Toxicity evaluation method of the present invention has good accuracy and comprehensive.By method of the present invention, can be easy, quickly and accurately the Cardiovascular Toxicity of conventional medicament is estimated prediction, it is a large amount of in time and fund aspect safety of medicine to be that the research and development of conventional medicament are saved.Simultaneously, use method of the present invention to improve for the conventional medicament prescription that has in usefulness, improve its drug safety.
According to said method of the present invention, the conventional medicament prescription is carried out Cardiovascular Toxicity evaluation prediction, drawing the Cardiovascular Toxicity evaluation predicts the outcome, according to described result, for the larger chemical constitution of toxicity, find component corresponding in the conventional medicament, adopt the similar component of therapeutic action to replace the larger component of described conventional medicament prescription Poisoning, provide the improvement of conventional medicament is guided, the conventional medicament prescription is improved, keep the purpose of drug effect when reducing toxic and side effect.
Embodiment three
In order to specify further the performance of method of evaluation and forecast of the present invention and system, select conventional medicament " yncaria stem with hooks " to be illustrated in present embodiment three, the below describes in detail and uses method of the present invention and prognoses system how the Cardiovascular Toxicity of " yncaria stem with hooks " to be estimated.
A specific embodiment of method of the present invention and prognoses system as shown in Figure 5.This embodiment is the concrete conventional medicament Cardiovascular Toxicity evaluation system of setting up according to previous embodiment of the present invention---" the internationalization of tcm Cardiovascular Toxicity is estimated integrated information system ", in the present embodiment, the concrete introduction uses described " the Chinese Native Medicine InternationalizationStrategy Cardiovascular Toxicity is estimated integrated information system " that yncaria stem with hooks is carried out the situation that Cardiovascular Toxicity is estimated.
In order to specify further the performance of evaluation method of the present invention and system, in present embodiment three, select conventional medicament--Chinese medicine " yncaria stem with hooks " is illustrated, and the below describes in detail and uses method of the present invention and prognoses system how the toxicity of " yncaria stem with hooks " to be estimated.
Yncaria stem with hooks has another name called hook fourth, ramulus uncariae rhynchophyllae, and for madder wort yncaria stem with hooks or Uncaria sinensis and belong to the buckle branch of various plants together, all on the books in multi-section conventional medicament ancient books and records, traditional effect is: the flat liver of heat-clearing; Relieving convulsion and spasm.Cure mainly child convulsion; The morbid night crying of babies; Heat is contained moving wind; Eclampsia; Dizziness due to hyperactivity of liver-YANG; Irascibility distending pain in the head etc.
1, data in literature Evaluation subsystem
With " yncaria stem with hooks " input data in literature Evaluation subsystem, obtain prediction address and be:
From bibliographic data base, retrieve and contain the compound of having reported in the yncaria stem with hooks and have 113 kinds.
Retrieve the toxicity of conventional medicament yncaria stem with hooks from bibliographic data base: the median lethal dose of 1 lumbar injection of mouse: the yncaria stem with hooks decoction is 29.0 native 0.8g/kg; Rhomotoxine is l44.2 soil 3.1mg/kg; Rhynchophyllin is 162.3mg/kg; Total alkali is oral to be 514.6 native 29.1mg/kg.Yncaria stem with hooks have reduce blood pressure, the possibility of the Cardiovascular such as proarrhythmia is very high, even gets rid of the effect with aspects such as carcinogenic teratogenesis.
2, chemical constitution toxicity assessment subsystem
With " yncaria stem with hooks " input chemical constitution toxicity assessment subsystem, obtain prediction address and be:
Compound Cardiovascular Toxicity prediction module prediction address shows: be made as in the structural similarity threshold value under 70% the condition, contained 23 compounds and known drug molecule with Cardiovascular Toxicity have similarity in the yncaria stem with hooks.Specifically comprise following several situation: result for retrieval shows that the catechol that contains in the yncaria stem with hooks has multiple danger: the rising blood pressure, cause tachycardia, haemolysis; Some compounds in the yncaria stem with hooks may have complicated Cardiovascular System; A compound in the yncaria stem with hooks may have carcinogenic teratogenesis toxicity; Yncaria stem with hooks contains multiple types like the cardiac glycoside structural compounds; A compound in the yncaria stem with hooks may cause low blood pressure, bradycardia; A kind of compound in the yncaria stem with hooks may cause heart QT interval to prolong.
Compound hERG blocking effect prediction module prediction address shows: the compound of having reported in the yncaria stem with hooks has 113 kinds, and wherein 32 compounds have hERG potassium-channel blocking-up feature structure.
The final appraisal report of chemical constitution toxicity assessment subsystem is: the multiple compounds that contains in the yncaria stem with hooks has analog structure with the medicine with cardiac vascular activity.Therefore, yncaria stem with hooks have reduce blood pressure, the possibility of the Cardiovascular such as proarrhythmia is very high, even gets rid of the effect with aspects such as carcinogenic teratogenesis.Contain 32 natural productss with hERG potassium-channel blocking-up feature structure in the yncaria stem with hooks, therefore, the possibility with QT prolongation effect is very high, and the risk of Cardiovascular Toxicity is also corresponding higher.
3, zoopery Evaluation subsystem
Animal experimental model is an important link in " the Chinese Native Medicine InternationalizationStrategy Cardiovascular Toxicity is estimated integrated information system ", builds together in the native system and has found cavy, beasle dog and three kinds of animal used as test platforms of New Zealand white rabbit.The below is the toxicological experiment result of yncaria stem with hooks on three kinds of animals.
The toxicological experiment result of yncaria stem with hooks on three kinds of animals
Experimental data is stored in the animal experimental data storehouse, the processing of throughput effect relationship module:
A. set up matched curve according to yncaria stem with hooks cavy, beasle dog, white rabbit experimental result, the conventional medicament dosage that obtains QTc prolongation 7.5% by curvilinear equation is respectively 10.1mg/kg, 2.8mg/kg, 4.1mg/kg;
B. by animal model Data Extrapolation people's dose,equivalent
End user-mouse reduction formula obtains, and people's dose,equivalent is 209.1mg/kg.
End user-rabbit reduction formula obtains, and people's dose,equivalent is 45.5mg/kg.
End user-dog reduction formula obtains, and people's dose,equivalent is 16.2mg/kg.
More approaching by the result that dog, rabbit experimental data obtain, cavy experimental result and other two kinds of animal diversity ratios are larger, may be because cavy insensitive to active component in the yncaria stem with hooks due to.Get the final result who predicts of mean value conduct of the experimental result of beasle dog and white rabbit.Be yncaria stem with hooks to cause people's QT to prolong 7.5% dosage be 30.8mg/kg, by body weight for humans 60kg, oral administration calculates, the minimal security metering that the normal person once takes in yncaria stem with hooks for 7.4g(by conventional medicament standard extract granule measurement).
4, the comprehensive evaluation module produces appraisal report
The prediction address of comprehensive above-mentioned three subsystems, the Cardiovascular Toxicity evaluation result that finally obtains the conventional medicament yncaria stem with hooks by the comprehensive evaluation module is: this conventional medicament is a kind ofly to have than the vasoactive medicine of cardiac stimulant, the various active composition that it contains all can produce the effect of cardiovascular aspect, suggestion should be used this medicine cautiously for the patient that angiocardiopathy is arranged, and the every day of this medicine, maximum intake should be pressed conventional medicament standard extract granule measurement less than 7.4g().
Embodiment four
Present embodiment is 1-4 by reference to the accompanying drawings, and the concrete grammar that utilizes conventional medicament Cardiovascular Toxicity evaluation system of the present invention to carry out the prediction of conventional medicament Cardiovascular Toxicity is described.
Conventional medicament Cardiovascular Toxicity evaluation system of the present invention shown in the 1-4 is estimated for conventional medicament with reference to the accompanying drawings.
Concrete steps comprise: (1) starts conventional medicament Cardiovascular Toxicity evaluation system, newly-built system's runnable interface; (2) in input window, input a traditional medicine name, perhaps consist of a series of traditional medicine names of a prescription; (3) system judges according to backstage conventional medicament noun list whether the traditional medicine name of input is correct, if correctly then continue, otherwise returns step (2), revises the traditional medicine name of inputting; (4) the data in literature Evaluation subsystem carries out literature search according to the traditional medicine name of input, and produces the evaluation result of literature search; (5) chemical constitution toxicity assessment subsystem is gathered according to the chemical constitution that the traditional medicine name of inputting obtains described conventional medicament, and the chemical constitution in this set is analyzed toxicity one by one, generates at last chemical constitution Cardiovascular Toxicity appraisal report; (6) the zoopery Evaluation subsystem is introduced experiment porch with medicine to be predicted, obtains experimental data two or more animals used as test, and throughput effect relationship resume module forms the Report on Animal of medicine to be predicted; (7) the comprehensive evaluation module gathers above-mentioned three parts of appraisal reports, forms the final appraisal report to medicine to be predicted.
Preferably, each stage and final appraisal results can perhaps form destination file by the display device output of computer platform, are stored on the memory device of computer platform; Subsystems is mutually independent, but user's combination in any is estimated the generation evaluation result.
Above-mentioned embodiment only is illustrative description, be not be intended to be exhaustive or the restriction the present invention, to those skilled in the art, it is apparent carrying out within the spirit and scope of the present invention many modifications, variation or replacement.Carrying out that embodiment is described in detail only is in order to explain better principle of the present invention.
Claims (18)
1. a conventional medicament Cardiovascular Toxicity is estimated prognoses system, and it is characterized in that: described system comprises:
The data in literature Evaluation subsystem is used for conventional medicament to be measured and active drug composition thereof are carried out the literature search analysis, filter out conventional medicament and effectively chemical constitution have a Cardiovascular Toxicity report;
Chemical constitution toxicity assessment subsystem is used for converting conventional medicament to be measured to the chemical constitution set, for the chemical constitution of medicine to be predicted, carries out the evaluation prediction of Cardiovascular Toxicity;
Described zoopery Evaluation subsystem, be used for medicine to be predicted is carried out zoopery, draw the animal used as test data of conventional medicament Cardiovascular Toxicity prediction, set up the dose-effect relationship model, extrapolation obtains people's minimum safe metering, estimates accordingly the Cardiovascular Toxicity of medicine;
Described comprehensive evaluation module is used for the evaluation result of described each subsystem is carried out analysis-by-synthesis, judges the Cardiovascular Toxicity of estimating described conventional medicament, and response user's various operations;
Described comprehensive evaluation module is connected with each described subsystem.
2. the system as claimed in claim 1 is characterized in that, described data in literature Evaluation subsystem comprises:
Load module is used for input and analysis conventional medicine and conventional medicament prescription information, and response user's various operations;
Conventional medicament database: be used for store and management conventional medicament related data;
Data processing module is used for finishing the analysis of conventional medicament to be predicted and conventional medicament prescription, and response user's various operations.
3. system as claimed in claim 2 is characterized in that, described load module also comprises:
Conventional medicament noun list is used for storing rectification of name, another name and the database login number of every kind of conventional medicament, and the data of input are carried out real-time analysis, and the traditional medicine name of user's input is converted into the accession number sequence, is used for the retrieval in later stage;
Traditional medicine name prompting submodule is used for the data according to above-mentioned conventional medicament noun list, inputs the user that the form with drop-down list provides real-time prompting in the process of traditional medicine name, to raise the efficiency, to reduce mistake;
Described conventional medicament database comprises following word bank:
The conventional medicament natural products database is for molecular structure and the biologically active data of store and management conventional medicament natural products; Scientific and technological literature database is used for the store and management Chinese and English scientific and technical literature data relevant with the medicine Cardiovascular Toxicity;
The FDA drug data base is used for all drug study data that store and management FDA reports;
Pharmaceutical control and administration rules database is used for the store and management countries in the world pharmaceutical control and administration rules relevant with the medicine Cardiovascular Toxicity;
World's conventional medicament patent database is used for store and management and worldwide conventional medicament patent.
4. the system as claimed in claim 1 is characterized in that, described chemical constitution Evaluation subsystem comprises at least:
All known toxicity of compound data have been collected in toxicity of compound storehouse, described toxicity of compound storehouse;
Chemical constitution Cardiovascular Toxicity evaluation module, described chemical constitution Cardiovascular Toxicity evaluation module carry out the evaluation prediction of toxicity of compound by the method for Chemoinformatics.
5. prognoses system as claimed in claim 1 is characterized in that, described chemical constitution Evaluation subsystem comprises at least:
Compound Cardiovascular Toxicity prediction module by adopting chemical molecular structural similarity algorithm, realizes the quantitative evaluation prediction of chemical constitution Cardiovascular Toxicity;
Compound hERG blocking effect prediction module by adopting chemical feature Structure Identification algorithm, realizes chemical constitution Cardiovascular Toxicity qualitative evaluation;
Predict the outcome and gather submodule, be used for gathering result of calculation, form prediction conclusion.
6. system as claimed in claim 5 is characterized in that:
Described compound Cardiovascular Toxicity prediction module comprises compound Cardiovascular Toxicity storehouse, has collected all known compound data messages with Cardiovascular Toxicity in the described compound Cardiovascular Toxicity storehouse;
Described compound hEGR blocking effect prediction module comprises Cardiovascular Toxicity molecular characterization storehouse, and described Cardiovascular Toxicity molecular characterization storehouse has the molecular characterization related data information of known Cardiovascular Toxicity.
7. prognoses system as claimed in claim 6 is characterized in that:
Described Cardiovascular Toxicity molecular characterization storehouse comprises:
The property estimated feature database: be used for the storage known molecular architectural feature relevant with the property estimated, described molecular characterization comprises: macrocyclic antibiotic, polypeptide, bridged ring micromolecular, mineral compound and molecular weight are greater than the chemical molecular architectural feature of 800 medicine;
The low activity feature database: be used for storing relevant known low hERG blocking-up bioactive molecule architectural feature, described low hERG blocking-up living features comprises: carboxyl, azido, alkynyl;
The high activity feature database: be used for storing relevant known high hERG blocking-up bioactive molecule architectural feature, described high hERG blocking-up living features comprises: phenyl ethylamine, amphetamine.
8. prognoses system as claimed in claim 7 is characterized in that: described high hERG blocking-up active structure feature also comprises the characterization of molecules structure:
Wherein A1 can be C, N or O atom independently of one another, and
A wherein
2Can be C, N or O atom independently of one another;
Described feature structure is a minor structure, is present in the organic molecule; Link to each other by 5 chemical bonds between phenyl ring and the terminal N atom, wherein chemical bond can be singly-bound, two key, triple bond, aromatic gp; Wherein said feature structure can not form a closed-loop construct by other atoms or chemical bond connection.
9. prognoses system as claimed in claim 1 is characterized in that, described zoopery Evaluation subsystem comprises at least:
The zoopery platform of conventional medicament is used for the animal experimental data collection, and animal used as test comprises: cavy, New Zealand white rabbit, beasle dog;
The animal model experiment database is used for storage animal model experiment data;
The dose-effect relationship module is used for zooperal data analysis, sets up dose-effect relationship.
10. the system as claimed in claim 1 is characterized in that, the comprehensive evaluation module comprises at least:
Load module is used for input data in literature Evaluation subsystem, the evaluation result of Chemical Evaluation subsystem, the evaluation result of zoopery Evaluation subsystem;
The comprehensive evaluation data processing module, for the qualitative analysis of the Cardiovascular Toxicity of finishing conventional medicament to be predicted, and response user's various operations.
11. such as the described evaluation system of one of claim 1-10, it is characterized in that, described each subsystem is related with computer platform with the comprehensive evaluation module, described data in literature Evaluation subsystem, chemical constitution toxicity assessment subsystem, zoopery Evaluation subsystem are mutually independent, the user is Selection and Constitute arbitrarily, produces required predicting the outcome.
12. the method for evaluation and forecast of a conventional medicament Cardiovascular Toxicity comprises the steps:
Step 1 is carried out the literature search analysis to conventional medicament to be measured and active drug composition thereof, filters out the related cardiovascular toxicity report of this conventional medicament and effective chemical constitution thereof;
Step 2 converts conventional medicament to be measured to the chemical composition data set, for the chemical constitution of medicine to be predicted, carries out one by one the evaluation prediction of Cardiovascular Toxicity;
Step 3 is carried out zoopery to medicine to be predicted, draws the animal used as test data of conventional medicament Cardiovascular Toxicity prediction, sets up the dose-effect relationship model, and extrapolation obtains people's minimum safe metering, estimates accordingly the Cardiovascular Toxicity of medicine;
Step 4, the result of comprehensive above-mentioned steps carries out comprehensive evaluation, judges the Cardiovascular Toxicity of the described conventional medicament of prediction;
Wherein, the order of step 1, step 2, step 3 in no particular order.
13. method as claimed in claim 12 is characterized in that:
Described step 1, step 2, step 3 are separate, can independent assortment;
In step 2, adopt the Chemoinformatics method to carry out the evaluation prediction of Cardiovascular Toxicity, for the chemical constitution Cardiovascular Toxicity of conventional medicament to be measured quantitatively, the qualitative evaluation prediction.
14. such as claim 11 or 12 described methods, it is characterized in that:
In step 2, by for the molecular structure similarity comparison of chemical constitution and/or the identification of chemical feature structure, carry out the evaluation prediction of conventional medicament toxicity.
15. method as claimed in claim 14 is characterized in that:
In the step 2, described molecular structure similarity relatively, to adopt chemical molecular structural similarity algorithm, molecular structure and known molecular structure of compounds with Cardiovascular Toxicity to conventional medicament chemical constitution to be measured carry out similarity relatively, draw the probability that conventional medicament to be measured has Cardiovascular Toxicity; The identification of described chemical feature structure is to adopt chemical feature Structure Identification algorithm, and the compound for the treatment of test and appraisal carries out the feature structure of hERG potassium-channel blocking effect and carries out identification, qualitatively judges accordingly compound and whether has Cardiovascular Toxicity.
16. a method of utilizing conventional medicament Cardiovascular Toxicity evaluation method that the conventional medicament prescription is improved is characterized in that:
Step 1 utilizes the conventional medicament evaluation method that the conventional medicament prescription is carried out Cardiovascular Toxicity evaluation prediction, draws to predict the outcome;
Step 2 predicts the outcome according to described evaluation, for the larger chemical constitution of toxicity, finds component corresponding in the conventional medicament,
Adopt the similar component of therapeutic action to replace the larger component of described conventional medicament prescription Poisoning, the conventional medicament prescription is improved.
17. one kind is utilized the conventional medicament Cardiovascular Toxicity to estimate the method that prognoses system is carried out the prediction of conventional medicament Cardiovascular Toxicity, it is characterized in that:
The concrete steps of described method comprise:
(1) starts the conventional medicament Cardiovascular Toxicity and estimate prognoses system, newly-built system's runnable interface;
(2) in input window, input a traditional medicine name, perhaps consist of a series of traditional medicine names of a prescription;
(3) system judges according to backstage conventional medicament noun list whether the traditional medicine name of input is correct, if correctly then continue, otherwise returns step (2), revises the traditional medicine name of inputting;
(4) the data in literature Evaluation subsystem carries out literature search according to the traditional medicine name of input, and produces the literature review prediction address of the Cardiovascular Toxicity of described conventional medicament;
(5) chemical constitution toxicity assessment subsystem is gathered according to the chemical constitution that the traditional medicine name of inputting obtains described conventional medicament, and described chemical constitution is carried out the Cardiovascular Toxicity evaluation one by one, generates at last chemical constitution Cardiovascular Toxicity appraisal report;
(6) the zoopery Evaluation subsystem is introduced experiment porch with medicine to be predicted, obtains experimental data by many animals is carried out animal used as test, forms the zoopery appraisal report of medicine to be predicted;
(7) the comprehensive evaluation module gathers above-mentioned three parts of appraisal reports, forms the final appraisal report to medicine to be predicted.
18. method as claimed in claim 17 is characterized in that:
Each stage reaches and finally predicts the outcome, and can perhaps form destination file by the display device output of computer platform, is stored on the memory device of computer platform;
Described data in literature Evaluation subsystem, chemical constitution toxicity assessment subsystem, zoopery Evaluation subsystem are mutually independent, but user's combination in any, and generation predicts the outcome.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106108846A (en) * | 2016-06-20 | 2016-11-16 | 中山大学 | A kind of intelligent drug risk monitoring method and system |
| CN110956625A (en) * | 2019-12-02 | 2020-04-03 | 中山大学 | Method for evaluating vascular toxicity of aryl phosphate flame retardant based on high content imaging system |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101201847A (en) * | 2007-12-26 | 2008-06-18 | 北京东方灵盾科技有限公司 | System and method for searching conventional medicament patent information |
| US20090068687A1 (en) * | 2004-01-14 | 2009-03-12 | The Hong Kong Polytechnic University | Screening platform for discovery of immunomodulatory activities in traditional medicine |
| WO2009036387A1 (en) * | 2007-09-14 | 2009-03-19 | Leung Albert Y | System and method for assessing traditional medicines |
| CN101443771A (en) * | 2004-12-16 | 2009-05-27 | 新星筛生物科技公司 | Method for identification and functional characterization of agents which modulate ion channel activity |
| CN101615222A (en) * | 2008-06-23 | 2009-12-30 | 中国医学科学院放射医学研究所 | A kind of Chinese prescription designing technique based on the Chinese medicine effective component group |
| CN101751479A (en) * | 2010-01-27 | 2010-06-23 | 北京东方灵盾科技有限公司 | Similarity matching system for prescription information of traditional medicine patents and matching method thereof |
| CN102609586A (en) * | 2012-02-10 | 2012-07-25 | 王世范 | New drug creating method |
-
2013
- 2013-01-26 CN CN2013100312032A patent/CN103077322A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090068687A1 (en) * | 2004-01-14 | 2009-03-12 | The Hong Kong Polytechnic University | Screening platform for discovery of immunomodulatory activities in traditional medicine |
| CN101443771A (en) * | 2004-12-16 | 2009-05-27 | 新星筛生物科技公司 | Method for identification and functional characterization of agents which modulate ion channel activity |
| WO2009036387A1 (en) * | 2007-09-14 | 2009-03-19 | Leung Albert Y | System and method for assessing traditional medicines |
| CN101201847A (en) * | 2007-12-26 | 2008-06-18 | 北京东方灵盾科技有限公司 | System and method for searching conventional medicament patent information |
| CN101615222A (en) * | 2008-06-23 | 2009-12-30 | 中国医学科学院放射医学研究所 | A kind of Chinese prescription designing technique based on the Chinese medicine effective component group |
| CN101751479A (en) * | 2010-01-27 | 2010-06-23 | 北京东方灵盾科技有限公司 | Similarity matching system for prescription information of traditional medicine patents and matching method thereof |
| CN102609586A (en) * | 2012-02-10 | 2012-07-25 | 王世范 | New drug creating method |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106108846A (en) * | 2016-06-20 | 2016-11-16 | 中山大学 | A kind of intelligent drug risk monitoring method and system |
| CN110956625A (en) * | 2019-12-02 | 2020-04-03 | 中山大学 | Method for evaluating vascular toxicity of aryl phosphate flame retardant based on high content imaging system |
| CN110956625B (en) * | 2019-12-02 | 2021-10-19 | 中山大学 | Method for evaluating vascular toxicity of aryl phosphate flame retardant based on high content imaging system |
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