CN102183608A - Traditional Chinese medicine pharmacokinetics-pharmacodynamics combined analysis method - Google Patents
Traditional Chinese medicine pharmacokinetics-pharmacodynamics combined analysis method Download PDFInfo
- Publication number
- CN102183608A CN102183608A CN2011100462581A CN201110046258A CN102183608A CN 102183608 A CN102183608 A CN 102183608A CN 2011100462581 A CN2011100462581 A CN 2011100462581A CN 201110046258 A CN201110046258 A CN 201110046258A CN 102183608 A CN102183608 A CN 102183608A
- Authority
- CN
- China
- Prior art keywords
- group
- chinese medicine
- model
- ginsenoside
- pharmacodynamics
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Abstract
The invention provides a traditional Chinese medicine pharmacokinetics-pharmacodynamics combined analysis method, which determines various endogenous metabolites in blood samples of a blank control group, a model group and a model treatment group by a GC-MS method, uses an abnormally-changed metabolite group of the model group as a biomarker group, uses an effect index with obvious callback of the abnormally-changed metabolite group after traditional Chinese medicine intervention as an efficacy marker group, determines the contents of various drugs in the blood samples of a model animal after single dose by a LC-MS method, draws a plasma concentration-time curve, calculates the pharmacokinetic parameters of each component; determines the amount of the endogenous efficacy marker group in the blood samples of the model animal single dose group by a GC-MS method, draws a time-effect curve, performs PK-PD combined analysis by combining with the plasma concentration-time curve and parameters. The invention reveals the efficacy substance base of traditional Chinese medicine in the treatment of cardiovascular diseases, and provides an effective method for traditional Chinese medicine pharmacokinetics-pharmacodynamics combined analysis.
Description
Technical field
The invention belongs to the science of Chinese materia medica research field, relate to Chinese medicine pharmacokinetics-pharmacodynamics (Pharmacokinetics-Pharacodynamics, PK-PD) Conjoint Analysis method, relate in particular to a kind of pharmacokinetics-pharmacodynamics Conjoint Analysis method for the treatment of angiocardiopathy Chinese medicine, can be used for the pharmacokinetics-pharmacodynamics joint study of complicated Chinese medicine.
Technical background
Pharmacokinetics-pharmacodynamics can be inquired into body to the effect to body of the effect (PK) of medicine and medicine simultaneously in conjunction with research, disclose the relation between drug concentration-time-effect three, thereby the experimental basis of science is provided for clinical safety, medication effectively and reasonably.
Current PK-PD has obtained certain progress in conjunction with research and application thereof, have to be solved yet PK-PD research still faces some problems, matter of utmost importance is how to seek and select suitable quantifiable pharmacodynamics index to estimate the curative effect of medicine, because the direct continuous and quantitative mensuration of the effect of many medicines; Next is multicomponent medicine (as a herbal mixture), has the characteristic of many target spots, many treatments approach, but because its complicated component, most effective substances and mechanism of action are very not clear and definite, and this has greatly limited research and the application of its PK-PD.Therefore be necessary to set up meet Chinese medicine multicomponent characteristic PK-PD in conjunction with the research new method, for the PK-PD of Chinese medicine provides technical support in conjunction with research.
Summary of the invention
The objective of the invention is deficiency, a kind of Chinese medicine pharmacokinetics-pharmacodynamics Conjoint Analysis method be provided, realize by following steps at above-mentioned prior art existence:
(1) myocardial ischemia disease biomarker group and drug effect label group's determines
Get rat, be divided into 3 groups at random, be respectively: blank group, model group and model administration group, the back all adopts intravenous injection isoprel or coronary artery left anterior descending branch desmurgia to make myocardial ischemia disease rat model for 2 groups, and model administration group again vein give the treatment by Chinese herbs intervention, gather 3 group blood samples, adopt gas-matter coupling method to measure blank group, model group, each endogenous metabolism thing in the model administration group blood sample, the blank group of contrast earlier, the variation of model group metabolite profile, find out the metabolin group of model group ANOMALOUS VARIATIONS, as myocardial ischemia disease biomarker group; The variation of contrast model group, model administration group metabolite profile again, find out the Chinese medicine intervention after ANOMALOUS VARIATIONS metabolin group adjust back tangible effect index as this herbal medicine efficacy label group;
(2) animal pattern Chinese medicine pharmacokinetic
The myocardial ischemia disease model rat of coring, the single vein gives the treatment by Chinese herbs intervention, in different time points: 10 min, 30 min, 1 h, 2 h, 4 h, 8 h, 24 h gather blood, adopt the LC-MS method to measure the concentration of each composition of Chinese medicine in each time point blood sample, draw pharmaceutical concentration-time curve, calculate each composition pharmacokinetic parameters;
(3) metabolin dynamics research behind the Chinese medicine therapeutic intervention
Get the same blood sample of step (2), adopt the gas chromatography mass spectrometry method to divide rating model administration group rat corresponding to endogenous drug effect label group in the pharmacokinetics time point blood sample, draw its each endogenous metabolism thing of herbal medicine efficacy label group of model administration group the time-the effect curve;
(4) Chinese medicine pharmacokinetics-pharmacodynamics Conjoint Analysis
Each composition pharmaceutical concentration-time curve of Chinese medicine that step (2) is obtained and step (3) acquisition the time-the effect curve carries out the Pearson correlation analysis, investigate of the influence of each composition to drug effect label group, if a certain component blood concentration is negative correlation to the regulating action of drug effect label, show that this composition has the readjustment effect to the drug effect label, belong to effective substance, negative correlation coefficient is big more, and effect is strong more.Disclose the effective substance of treatment angiocardiopathy Chinese medicine by the PK-PD Conjoint Analysis.
The invention provides a kind of PK-PD combination model research new method for the treatment of angiocardiopathy Chinese medicine.Usually Chinese medicine has the characteristic of many target spots, many treatments approach, and because its complicated component, most study on mechanism are still very not clear and definite, and result of treatment is difficult to directly quantize in the PK-PD model.Usefulness of the present invention: the adoption of innovation metabonomic technology, substitute index with the quantifiable endogenous metabolism thing group relevant as drug effect with curative effect, carry out PK-PD in conjunction with research, disclose the herbal medicine efficacy material base.The Chinese medicine preparation that is specially adapted to complicated component, curative effect and is the multicomponent combined action is carried out the PK-PD correlation research.
Description of drawings
Fig. 1 is the rat plasma metabolite profile that gas chromatography mass spectrometry is measured.
Fig. 2 is Chinese medicine XUESAITONG ZHUSHEYE principal ingredient ginsenoside Rd, Rb1, the Rb2 blood concentration-time curve in myocardial ischemia disease model rat body.
Fig. 3 is Chinese medicine XUESAITONG ZHUSHEYE principal ingredient notoginsenoside R, ginsenoside Rg1, Re, Rg2, Rh1,20(S)-Rg3,20(R)-blood concentration-time curve of Rg3 in myocardial ischemia disease model rat body.
Fig. 4 is the logical injection intervention group drug effect label group time of myocardial ischemia disease model thromboembolism-effect curve (n=5), and wherein ordinate is the ratio of metabolin peak area and interior mark peak area, and horizontal ordinate is each sampling time point.
Embodiment
The invention will be further described below in conjunction with embodiment and accompanying drawing.
(1) gets 15 of SD rats, be divided into 3 groups at random, be respectively: blank group, model group and model administration group.Model group and model administration group are to adopt coronary artery left anterior descending branch desmurgia to make the myocardial ischemia disease model, and model administration group is in modeling subcutaneous XUESAITONG ZHUSHEYE that gives of single dose side lower abdomen after 7 days, 18mg/kg.It is standby that blank group, model group and model administration group are all gathered blood plasma.Each endogenous metabolism thing spectrum is (referring to accompanying drawing 1 in the employing gas chromatography mass spectrometry method mensuration blood plasma, wherein a is blank group, b is a myocardial ischemia disease model group), the blank group of contrast earlier, the variation of model group metabolite profile, find out the significant metabolin group of model group ANOMALOUS VARIATIONS, find 24 of disease biomarkers, be respectively lactic acid, glycerol 3-phosphate, glyceric acid, succinic acid, malic acid, 2,4-dihydroxy butyric acid, phosphoric acid, amidomalonic acid, threonine, 2,4-dihydroxy butyric acid, glycocoll, 2,3, the 4-trihydroxy-butyraldehyde, the 5-Pidolic Acid, phenylalanine, proline, the D-sorbierite, palmitic acid, octadecanoid acid, 1-palmityl glycerine, 1-18 acyl glycerine, vitamin E, urea, cholesterol, cupreol; The variation of contrast model group, model administration group metabolite profile again, find out in the blood plasma of the logical treatment intervention of thromboembolism back and adjust back 7 of tangible effect indexes, be respectively lactic acid, phosphoric acid, glycerine, succinic acid, glyceric acid, malic acid, cholesterol, these 7 indexs be decided to be the drug effect label group of the logical treatment of thromboembolism angiocardiopathy.Described model is meant the myocardial ischemia disease model.Model group and model administration group also can adopt the intravenous injection isoprel to make the myocardial ischemia disease model.
(2) Chinese medicine Study on Pharmacokinetics of Xuesaitong Injection
The myocardial ischemia disease model rat of coring, the single vein gives XUESAITONG ZHUSHEYE 18 mg/kg therapeutic interventions, collect plasma sample in 10 min, 30 min, 1 h, 2 h, 4 h, 8 h, 24 h, adopt liquid-matter coupling method to measure 12 main saponin constituent (Panax Notoginseng saponin Rs of XUESAITONG ZHUSHEYE
1, ginsenoside Rb
1, Rc, Rb
2, Rb
3, Rd, Rg
1, Re, Rh
1, Rg
2, 20 (R)-Rg
3, 20 (S)-Rg
3) concentration in each time point plasma sample, draw blood concentration-time curve (referring to accompanying drawing 2, Fig. 3), calculate each composition pharmacokinetic parameters (table 1).
Liquid-matter coupling method is measured 12 main saponin constituent methods of XUESAITONG ZHUSHEYE:
1) instrument Agilent 1100 liquid chromatographs-Agilent 6410B triple quadrupole bar tandem mass spectrometer (U.S. Agilent company); Thermo Savant SPD121P centrifuge concentrator (U.S. Thermo company); Milli-Q ultrapure water system (U.S. Millipore company).
2) test sample preparation: precision is measured blood plasma 100 μ L to be measured in 1.5 mL centrifuge tubes, accurate 20 μ g/mL digoxin inner mark solution 10 μ L and the 300 μ L methyl alcohol of adding, and vortex mixing 2 min, it is standby to draw supernatant behind centrifugal 15 min of 13000 r/min.
3) chromatogram and mass spectrum condition
Chromatographic condition: chromatographic column is Zorbax SB-C
18Post (50 mm * 2.1 mm, 3.5m).Adopt 0.01% acetic acid water-0.01% acetate acetonitrile gradient elution (0-6 min, 80:20; 10 min, 72:28; 20 min, 60:40; 27 min, 41:59; 30 min 15:85), get back to start gradient balance 8 min.Flow velocity 0.25 mL/min, 30 ℃ of column temperatures, sample size: 5 μ L.
Mass spectrum condition: electric spray ion source; Adopt the multiple-reaction monitoring pattern to detect under the negative ion condition, m/z is: notoginsenoside R: 931 → 637; Ginsenoside Rg1: 799 → 475; Ginsenoside Re: 945 → 637; Ginsenoside Rb1: 1107 → 945; Ginsenoside Rc: 1077 → 945; Ginsenoside Rg2: 783 → 475; Ginsenoside Rh 1: 637 → 475; Ginsenoside Rb2: 1077 → 783; Ginsenoside Rb3:1077 → 915; Ginsenoside Rd: 945 → 783; Ginsenoside SRg3:783 → 459; Ginseng sapoglycoside Rg 3: 783 → 459; Interior mark digoxin: 779 → 475.
(3) metabolin dynamics research behind the Chinese medicine therapeutic intervention
Get it filled and adopt the amount of 7 drug effect labels in gas-each pharmacokinetics time point blood plasma of matter coupling method rating model administration group for the same sample of dynamics research, during drafting-effect curve (referring to accompanying drawing 4a-g).
Gas chromatography mass spectrometry method analysed for plasma metabolite profile method:
1) instrument and reagent A gilent 6890/5973 gas chromatograph-mass spectrometer (GCMS) (U.S. Agilent company) are furnished with Agilent7683 automatic sampler and Agilent ZB-5 MS capillary column (0.25mm * 30 m * 0.25 μ m); Thermo Savant SPD121P centrifuge concentrator (U.S. Thermo company); Milli-Q ultrapure water system (U.S. Millipore company).
Pyridine, N methyl N trimethylsilyl trifluoroacetamide (MSTFA) and tri-methyl-chlorosilane (TMCS), methoxamine hydrochloride (analyze pure, U.S. Sigma-Aldrich company); Acetone, normal heptane (analyze pure, Hangzhou chemical reagent work); Pentitol (Shanghai chemical reagents corporation of traditional Chinese medicines group)
2) sample derivatization treatment precision is measured blood plasma 100 μ L to be measured in 1.5 mL centrifuge tubes, accurate 1 mg/mL pentitol inner mark solution, 10 μ L and the 200 μ L acetone of adding, vortex 1 min, treat ice-bath ultrasonic 15 min behind the abundant mixing, draw supernatant 200 μ L behind centrifugal 10 min of 10000 r/min in the sample introduction bottle, volatilize solvent at 40 ℃ of centrifugal down 3 h that concentrate.Add 15 mg/mL methoxamine pyridine solutions, 50 μ L, 70 ℃ of following oximate 1 h add 100 μ L normal heptanes then behind the mixing, draw supernatant to micro-sampling pipe behind the mixing and supply gas chromatography-mass spectrometry analysis.
3) gas chromatograph-mass spectrometer (GC-MS) condition injector temperature: 270 ℃; The column temperature heating schedule: initial temperature keeps 5 min for 70 ℃, is warming up to 100 ℃ with 10 ℃/min and keeps 5 min, and 10 ℃/min is warming up to 200 ℃ and keeps 10 min, and 10 ℃/min is warming up to 300 ℃ and keeps 10 min; Sample size: 1 μ L, not split sampling; Carrier gas is high-purity helium, flow velocity: 0.8 mL/min; Ion source temperature: 230 ℃; Level Four bar temperature: 150 ℃; Ionization voltage: 70 eV; Scan pattern: full scan, 60 ~ 600 m/z; Sweep velocity: 2 times/s.
(4) XUESAITONG ZHUSHEYE composition ginsenoside Rg
1The PK-PD Conjoint Analysis
With the ginsenoside Rg
1When blood concentration-time curve and above-mentioned 7 drug effect labels-the effect curve carries out the Pearson correlation analysis.The result is as shown in table 2 for its related coefficient (r).Negative correlation coefficient explanation ginsenoside Rg
1Blood concentration is negative correlation to the regulating action of drug effect label, and promptly negative correlation coefficient is big more, the ginsenoside Rg
1Readjustment effect to the respective markers thing accounts for main effect more.Therefore, by ginsenoside Rg as can be known in the table
1Lactic acid, succinic acid, malic acid, cholesterol there are the readjustment effect, especially lactic acid are had stronger regulating action, hence one can see that Rg
1Be one of main pharmacodynamics composition, its therapeutic action mainly is to recover glycolysis, tricarboxylic acid cycle homenergic metabolic pathway.
Embodiment 2
According to the method for embodiment 1, difference is the PK-PD Conjoint Analysis to XUESAITONG ZHUSHEYE composition notoginsenoside R
During with notoginsenoside R blood concentration-time curve and above-mentioned 7 drug effect labels-the effect curve carries out the Pearson correlation analysis.The result is as shown in table 3 for its related coefficient (r).Negative correlation coefficient explanation notoginsenoside R blood concentration is negative correlation to the regulating action of drug effect label, and promptly negative correlation coefficient is big more, and notoginsenoside R accounts for main effect more to the readjustment effect of respective markers thing.Therefore, by in the table as can be known notoginsenoside R lactic acid, succinic acid, malic acid, cholesterol had a readjustment effect, especially lactic acid there is stronger regulating action, hence one can see that, and R1 is one of main pharmacodynamics composition, and its therapeutic action mainly is to recover glycolysis, tricarboxylic acid cycle homenergic metabolic pathway.
Embodiment 3
According to the method for embodiment 1, difference is the PK-PD Conjoint Analysis to XUESAITONG ZHUSHEYE composition ginsenoside Re
During with ginsenoside Re's blood concentration-time curve and above-mentioned 7 drug effect labels-the effect curve carries out the Pearson correlation analysis.The result is as shown in table 4 for its related coefficient (r).Negative correlation coefficient explanation ginsenoside Re blood concentration is negative correlation to the regulating action of drug effect label, and promptly negative correlation coefficient is big more, and the ginsenoside Re accounts for main effect more to the readjustment effect of respective markers thing.Therefore, by in the table as can be known the ginsenoside Re lactic acid, succinic acid, malic acid, cholesterol had a readjustment effect, especially lactic acid there is stronger regulating action, hence one can see that, and Re is one of main pharmacodynamics composition, and its effect mainly is to recover glycolysis, tricarboxylic acid cycle homenergic metabolic pathway normal level.
。
Embodiment 4
According to the method for embodiment 1, difference is the PK-PD Conjoint Analysis to XUESAITONG ZHUSHEYE composition ginsenoside Rb1
During with ginsenoside Rb1's blood concentration-time curve and above-mentioned 7 drug effect labels-the effect curve carries out the Pearson correlation analysis.The result is as shown in table 5 for its related coefficient (r).Negative correlation coefficient explanation ginsenoside Rb1 blood concentration is negative correlation to the regulating action of drug effect label, and promptly negative correlation coefficient is big more, and the ginsenoside Rb1 accounts for main effect more to the readjustment effect of respective markers thing.Therefore, by the table in as can be known the ginsenoside Rb1 phosphoric acid, glyceric acid, cholesterol are had the readjustment effect, show that Rb1 is one of main pharmacodynamics composition.
According to the method for embodiment 1, difference is the PK-PD Conjoint Analysis to XUESAITONG ZHUSHEYE composition ginsenoside Rd
With ginsenoside Rd's medicine dense-when time curve and above-mentioned 7 drug effect labels-the effect curve carries out the Pearson correlation analysis.The result is as shown in table 6 for its related coefficient (r).Negative correlation coefficient explanation ginsenoside Rd blood concentration is negative correlation to the regulating action of drug effect label, and promptly negative correlation coefficient is big more, and the ginsenoside Rd accounts for main effect more to the readjustment effect of respective markers thing.Therefore, by the table in as can be known the ginsenoside Rd phosphoric acid, glyceric acid, cholesterol are had the readjustment effect, show that Rd is one of main pharmacodynamics composition.
Claims (6)
1. Chinese medicine pharmacokinetics-pharmacodynamics Conjoint Analysis method is characterized in that, realizes by following steps:
(1) biomarker group and drug effect label group's determines
Get rat, be divided into 3 groups at random, be respectively: blank group, model group and model administration group, the back all adopts intravenous injection isoprel or coronary artery left anterior descending branch desmurgia to build up rat model for 2 groups, and model administration group be after the modeling again vein give the treatment by Chinese herbs intervention, gather 3 group blood samples, adopt gas-matter coupling method to measure blank group, model group, each endogenous metabolism thing in the model administration group blood sample, the blank group of contrast earlier, the variation of model group metabolite profile, find out the metabolin group of model group ANOMALOUS VARIATIONS, as myocardial ischemia disease biomarker group; The variation of contrast model group, model administration group metabolite profile again, find out the Chinese medicine intervention after ANOMALOUS VARIATIONS metabolin group adjust back tangible effect index as this herbal medicine efficacy label group;
(2) animal pattern Chinese medicine pharmacokinetic
The myocardial ischemia disease model rat of coring, the single vein gives the treatment by Chinese herbs intervention, respectively at 10 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours collection blood, adopt the LC-MS method to measure the concentration of each composition of Chinese medicine in each time point blood sample, draw pharmaceutical concentration-time curve, calculate each composition pharmacokinetic parameters;
(3) metabolin dynamics research behind the Chinese medicine therapeutic intervention
Get the identical blood sample of step (2), adopt the gas chromatography mass spectrometry method to divide rating model administration group rat corresponding to endogenous drug effect label group in the pharmacokinetics time point blood sample, draw its each endogenous metabolism thing of herbal medicine efficacy label group of model administration group the time-the effect curve;
(4) Chinese medicine pharmacokinetics-pharmacodynamics Conjoint Analysis
Each composition pharmaceutical concentration-time curve of Chinese medicine that step (2) is obtained and step (3) acquisition the time-the effect curve carries out the Pearson correlation analysis, if a certain component blood concentration is negative correlation to the regulating action of drug effect label, show that this composition has the readjustment effect to the drug effect label, belong to effective substance, negative correlation coefficient is big more, and effect is strong more.
2. a kind of Chinese medicine pharmacokinetics according to claim 1-pharmacodynamics Conjoint Analysis method is characterized in that the described rat model of step (1) is meant the myocardial ischemia disease model.
3. a kind of Chinese medicine pharmacokinetics according to claim 1-pharmacodynamics Conjoint Analysis method, it is characterized in that, the treatment by Chinese herbs intervention of the described model administration of step (1) group is in modeling subcutaneous XUESAITONG ZHUSHEYE that gives of single dose side lower abdomen after 7 days, 18mg/kg.
4. a kind of Chinese medicine pharmacokinetics according to claim 1-pharmacodynamics Conjoint Analysis method, it is characterized in that chromatographic condition is: chromatographic column is Zorbax SB-C
18Post, 50 mm * 2.1 mm, 3.5 m; Adopt 0.01% acetic acid water-0.01% acetate acetonitrile gradient elution: 0-6 min, 80:20,10 min, 72:28,20 min, 60:40,27 min, 41:59,30 min, 15:85; Get back to start gradient balance 8 min, flow velocity 0.25 mL/min, 30 ℃ of column temperatures, sample size: 5 μ L.
5. a kind of Chinese medicine pharmacokinetics according to claim 1-pharmacodynamics Conjoint Analysis method is characterized in that the mass spectrum condition is: electric spray ion source; Adopt the multiple-reaction monitoring pattern to detect under the negative ion condition, m/z is: notoginsenoside R: 931 → 637; Ginsenoside Rg1: 799 → 475; Ginsenoside Re: 945 → 637; Ginsenoside Rb1: 1107 → 945; Ginsenoside Rc: 1077 → 945; Ginsenoside Rg2: 783 → 475; Ginsenoside Rh 1: 637 → 475; Ginsenoside Rb2: 1077 → 783; Ginsenoside Rb3:1077 → 915; Ginsenoside Rd: 945 → 783; Ginsenoside SRg3:783 → 459; Ginseng sapoglycoside Rg 3: 783 → 459; Interior mark digoxin: 779 → 475.
6. a kind of Chinese medicine pharmacokinetics according to claim 1-pharmacodynamics Conjoint Analysis method, it is characterized in that the gas chromatography combined with mass spectrometry condition: injector temperature is 270 ℃; The column temperature heating schedule is that initial temperature keeps 5 min for 70 ℃, is warming up to 100 ℃ with 10 ℃/min and keeps 5 min, and 10 ℃/min is warming up to 200 ℃ and keeps 10 min, and 10 ℃/min is warming up to 300 ℃ and keeps 10 min; Sample size: 1 μ L, not split sampling; Carrier gas is high-purity helium, flow velocity: 0.8 mL/min; Ion source temperature: 230 ℃; Level Four bar temperature: 150 ℃; Ionization voltage: 70 eV; Scan pattern: full scan, 60 ~ 600 m/z; Sweep velocity: 2 times/s.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100462581A CN102183608A (en) | 2011-02-27 | 2011-02-27 | Traditional Chinese medicine pharmacokinetics-pharmacodynamics combined analysis method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100462581A CN102183608A (en) | 2011-02-27 | 2011-02-27 | Traditional Chinese medicine pharmacokinetics-pharmacodynamics combined analysis method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102183608A true CN102183608A (en) | 2011-09-14 |
Family
ID=44569820
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011100462581A Pending CN102183608A (en) | 2011-02-27 | 2011-02-27 | Traditional Chinese medicine pharmacokinetics-pharmacodynamics combined analysis method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102183608A (en) |
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103399098A (en) * | 2013-08-13 | 2013-11-20 | 曹洪欣 | Evaluation method for rat model of heart-Qi deficiency syndrome |
| CN103969346A (en) * | 2013-01-25 | 2014-08-06 | 天士力制药集团股份有限公司 | Panax notoginseng saponin component analysis method |
| CN104833748A (en) * | 2014-02-11 | 2015-08-12 | 沈阳药科大学 | Multi-component high-flux quantitative analytic technology used for traditional Chinese medicine pharmacokinetic evaluation |
| CN106568910A (en) * | 2015-10-10 | 2017-04-19 | 成都中医药大学 | Construction method of traditional Chinese medicine integrated pharmacokinetic model |
| CN106682396A (en) * | 2016-12-09 | 2017-05-17 | 贵州医科大学 | Method for establishing PK-PD combination model of four representative components in traditional Chinese medicine formula |
| CN107064480A (en) * | 2016-08-12 | 2017-08-18 | 株洲千金药业股份有限公司 | Chinese medicinal ingredients act on azithromycin baseline lifting evaluation method and evaluate the application of gynaecology's prescriptions worth thousand gold |
| CN107247867A (en) * | 2017-05-15 | 2017-10-13 | 浙江大学 | A kind of discrimination method of Chinese medicine effect chemical marker group |
| CN107391927A (en) * | 2017-07-20 | 2017-11-24 | 京东方科技集团股份有限公司 | A kind of method and electronic equipment for predicting medicine and disease corresponding relation |
| CN108281182A (en) * | 2017-12-30 | 2018-07-13 | 广州柏颐信息科技有限公司 | A kind of user health monitoring data alarm method and device |
| CN109115933A (en) * | 2018-08-31 | 2019-01-01 | 中国人民解放军第四军医大学 | A method of screening Protective effects of Sini decoction myocardial ischemia effective substance |
| CN110607344A (en) * | 2019-09-03 | 2019-12-24 | 华中农业大学 | Construction method and application of veterinary antibacterial drug cefquinome PK/PD model |
| CN110658298A (en) * | 2019-11-12 | 2020-01-07 | 北京和合医学诊断技术股份有限公司 | Method for detecting digoxin in blood |
| CN113393944A (en) * | 2021-06-17 | 2021-09-14 | 中国科学院长春应用化学研究所 | Pharmacokinetic-pharmacodynamic analysis method for treating chronic heart failure by astragalus-ginseng particles based on metabonomics |
| CN114646691A (en) * | 2020-12-18 | 2022-06-21 | 中国科学院上海药物研究所 | Analysis method for simultaneously quantifying 15 ginsenoside components of Danqi Tongmai tablets in rat plasma |
| CN115472236A (en) * | 2022-10-19 | 2022-12-13 | 湖南中医药大学 | Method for determining, characterizing and evaluating pharmacodynamic substances by utilizing imprinting template component cluster dynamics and thermodynamic equilibrium principle |
-
2011
- 2011-02-27 CN CN2011100462581A patent/CN102183608A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| DJ ANGIOLILLO ETAL: "Differential Effects of Omeprazole and Pantoprazole on the Pharmacodynamics and Pharmacokinetics of Clopidogrel in Healthy Subjects: Randomized, Placebo-Controlled，Crossover Comparison Studies", 《CLINICAL PHARMACOLOGY & THERAPEUTICS》 * |
| LEE JIA ETAL: "Pharmacodynamics and pharmacokinetics of SQ109, a new diamine-based antitubercular drug", 《BRITISH JOURNAL OF PHARMACOLOGY》 * |
| 苏如雄 等: "药动学一药效学结合模型的应用进展", 《中国药房》 * |
Cited By (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103969346A (en) * | 2013-01-25 | 2014-08-06 | 天士力制药集团股份有限公司 | Panax notoginseng saponin component analysis method |
| CN103399098A (en) * | 2013-08-13 | 2013-11-20 | 曹洪欣 | Evaluation method for rat model of heart-Qi deficiency syndrome |
| CN104833748A (en) * | 2014-02-11 | 2015-08-12 | 沈阳药科大学 | Multi-component high-flux quantitative analytic technology used for traditional Chinese medicine pharmacokinetic evaluation |
| CN106568910A (en) * | 2015-10-10 | 2017-04-19 | 成都中医药大学 | Construction method of traditional Chinese medicine integrated pharmacokinetic model |
| CN107064480B (en) * | 2016-08-12 | 2019-05-03 | 株洲千金药业股份有限公司 | Chinese medicinal ingredients promote evaluation method to azithromycin effect baseline and evaluate the application of gynaecology's prescriptions worth thousand gold |
| CN107064480A (en) * | 2016-08-12 | 2017-08-18 | 株洲千金药业股份有限公司 | Chinese medicinal ingredients act on azithromycin baseline lifting evaluation method and evaluate the application of gynaecology's prescriptions worth thousand gold |
| CN106682396A (en) * | 2016-12-09 | 2017-05-17 | 贵州医科大学 | Method for establishing PK-PD combination model of four representative components in traditional Chinese medicine formula |
| CN107247867A (en) * | 2017-05-15 | 2017-10-13 | 浙江大学 | A kind of discrimination method of Chinese medicine effect chemical marker group |
| CN107247867B (en) * | 2017-05-15 | 2019-10-25 | 浙江大学 | A kind of discrimination method of Chinese medicine effect chemical marker group |
| CN107391927B (en) * | 2017-07-20 | 2021-01-22 | 京东方科技集团股份有限公司 | Method and electronic equipment for predicting corresponding relation between medicine and disease |
| CN107391927A (en) * | 2017-07-20 | 2017-11-24 | 京东方科技集团股份有限公司 | A kind of method and electronic equipment for predicting medicine and disease corresponding relation |
| CN108281182A (en) * | 2017-12-30 | 2018-07-13 | 广州柏颐信息科技有限公司 | A kind of user health monitoring data alarm method and device |
| CN108281182B (en) * | 2017-12-30 | 2021-10-08 | 广州爱牵挂数字科技有限公司 | User health monitoring data alarming method and device |
| CN109115933A (en) * | 2018-08-31 | 2019-01-01 | 中国人民解放军第四军医大学 | A method of screening Protective effects of Sini decoction myocardial ischemia effective substance |
| CN109115933B (en) * | 2018-08-31 | 2020-10-23 | 中国人民解放军第四军医大学 | Method for screening substance basis of anti-myocardial ischemia drug effect of Sini decoction |
| CN110607344A (en) * | 2019-09-03 | 2019-12-24 | 华中农业大学 | Construction method and application of veterinary antibacterial drug cefquinome PK/PD model |
| CN110658298A (en) * | 2019-11-12 | 2020-01-07 | 北京和合医学诊断技术股份有限公司 | Method for detecting digoxin in blood |
| CN114646691A (en) * | 2020-12-18 | 2022-06-21 | 中国科学院上海药物研究所 | Analysis method for simultaneously quantifying 15 ginsenoside components of Danqi Tongmai tablets in rat plasma |
| CN113393944A (en) * | 2021-06-17 | 2021-09-14 | 中国科学院长春应用化学研究所 | Pharmacokinetic-pharmacodynamic analysis method for treating chronic heart failure by astragalus-ginseng particles based on metabonomics |
| CN115472236A (en) * | 2022-10-19 | 2022-12-13 | 湖南中医药大学 | Method for determining, characterizing and evaluating pharmacodynamic substances by utilizing imprinting template component cluster dynamics and thermodynamic equilibrium principle |
| CN115472236B (en) * | 2022-10-19 | 2024-04-30 | 湖南中医药大学 | Method for determining, characterizing and evaluating drug effect substance by utilizing principle of clustering dynamics and thermodynamic equilibrium of imprinting template |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102183608A (en) | Traditional Chinese medicine pharmacokinetics-pharmacodynamics combined analysis method | |
| Li et al. | Ultra-high-performance liquid chromatography–quadrupole/time of flight mass spectrometry based chemical profiling approach to rapidly reveal chemical transformation of sulfur-fumigated medicinal herbs, a case study on white ginseng | |
| Zhang et al. | Simultaneous quantification of 17 constituents from Yuanhu Zhitong tablet using rapid resolution liquid chromatography coupled with a triple quadrupole electrospray tandem mass spectrometry | |
| Lai et al. | Comparative pharmacokinetic and bioavailability studies of three salvianolic acids after the administration of Salviae miltiorrhizae alone or with synthetical borneol in rats | |
| Wu et al. | Pharmacokinetic study of four flavones of Glycyrrhiza in rat plasma using HPLC–MS | |
| Lv et al. | Characterization of the constituents in rat biological fluids after oral administration of Fufang Danshen tablets by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry | |
| CN104614456A (en) | Method for simultaneously detecting main components of Naoxintong capsule in plasma | |
| Cao et al. | Identification of metabolites of crude and processed Fructus Corni in rats by microdialysis sampling coupled with electrospray ionization linear quadrupole ion trap mass spectrometry | |
| Li et al. | Global analysis of chemical constituents in Shengmai injection using high performance liquid chromatography coupled with tandem mass spectrometry | |
| Sun et al. | Pharmacokinetic study of ginsenoside Rc and simultaneous determination of its metabolites in rats using RRLC-Q-TOF-MS | |
| CN104914199A (en) | Determining method for contents of twelve components in traditional Chinese medicine composition preparation | |
| Chang et al. | Simultaneous determination of four phenolic acids and seven alkaloids in rat plasma after oral administration of traditional Chinese medicinal preparation Jinqi Jiangtang Tablet by LC-ESI–MS/MS | |
| Zheng et al. | Isolated perfused lung extraction and HPLC–ESI–MSn analysis for predicting bioactive components of Saposhnikoviae Radix | |
| Wen et al. | Analysis of Panax notoginseng metabolites in rat bile by liquid chromatography–quadrupole time-of-flight mass spectrometry with microdialysis sampling | |
| Hou et al. | Studies on the interactions between ginsenosides and liposome by equilibrium dialysis combined with ultrahigh performance liquid chromatography-tandem mass spectrometry | |
| Li et al. | Rapid characterization of the constituents in Jigucao capsule using ultra high performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry | |
| Li et al. | Simultaneous determination of three saponins in human plasma after oral administration of compound danshen dripping pills by LC-MS/MS and its application in a pharmacokinetic study | |
| CN104914173A (en) | Method for determining multiple components content in traditional Chinese medicine composition preparation | |
| Wang et al. | Recent advances in separation and analysis of saponins in natural products | |
| He et al. | Using 3D-UPLC-DAD and a new method-verification by adding mixture standard compounds to determine the fingerprint and eight active components of Naoluoxintong decoction | |
| Gao et al. | Simultaneous determination of nineteen major active compounds in Qiangshen tablet by UPLC-ESI-MS/MS | |
| CN104849369A (en) | Quality detection method of ephedra sinica-aconitum napellus-liquorice medicine | |
| Zhu et al. | Analysis of the chemical constituents and rats metabolites after oral administration of Nauclea officinalis by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry | |
| Wang et al. | Preclinical pharmacokinetics, tissue distribution and excretion studies of a potential analgesics–corydaline using an ultra performance liquid chromatography–tandem mass spectrometry | |
| Ren et al. | Qualitative and quantitative analysis of multi-components in Xing-Su-Ning Capsules for quality improvement |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20110914 |
|
| WD01 | Invention patent application deemed withdrawn after publication |