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Blood dialysate detection method, and application thereof in pharmacokinetics-pharmacodynamics of pulse activating injection

A technology of Shengmai injection and hemodialysis, applied in the field of medicine

Active Publication Date: 2018-08-03
JIAXING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, looking at the literature, there are still some obvious technical limitations in the application of microdialysis sampling technology to pharmacokinetic-pharmacodynamic studies.

Method used

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  • Blood dialysate detection method, and application thereof in pharmacokinetics-pharmacodynamics of pulse activating injection
  • Blood dialysate detection method, and application thereof in pharmacokinetics-pharmacodynamics of pulse activating injection
  • Blood dialysate detection method, and application thereof in pharmacokinetics-pharmacodynamics of pulse activating injection

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] 1. Reagents and instruments

[0052] 1. Drugs and reagents

[0053] The reference substances ginsenoside Rg1, ginsenoside Rg2, ginsenoside Re, ginsenoside Rf, ginsenoside Rb1, ginsenoside Rd and ginsenoside Rc were purchased from Shanghai Ronghe Pharmaceutical Technology Development Co., Ltd. Shengmai injection (concentrations of ginsenosides Rg1, Rg2, Re, Rf, Rb1, Rd and Rc were determined to be 140.8, 22.5, 79.8, 38.3, 140.0, 25.4 and 79.4 μg / mL, respectively) was produced by Changshu Leiyunshang Pharmaceutical Co., Ltd. Limited offer. Isoproterenol (Isoproterenol, ISO) was purchased from Sigma. The internal standard digoxin (digoxin) was purchased from China National Institutes for Food and Drug Control. Normal saline for injection was purchased from the Affiliated Hospital of Zhejiang University. Methanol and acetonitrile were chromatographically pure (Merck), acetic acid was chromatographically pure (Tedia), and deionized water was prepared by a Milli-Q ultrapu...

Embodiment 2

[0082] Embodiment 2 pharmacokinetic research results and discussion

[0083] 1. Methodological validation

[0084] 1. Optimization of mass spectrometry conditions

[0085] Optimization of mass spectrometry parameters: Prepare mixed standard solutions of ginsenosides Rg1, Rg2, Re, Rf, Rb1, Rd, Rc and internal standard (IS) with physiological saline, and perform mass spectrometry parameters declustering voltage (DP), entrance voltage (EP) respectively. ), collision energy (CE), and exit voltage (CXP), the optimal parameters are mainly selected according to the mass spectrum response size (intensity), and the optimization results are as follows: image 3 , Figure 4 , Figure 5 and Figure 6 shown.

[0086] According to the optimization results in the figure above, the DPs of ginsenosides Rg1, Rg2, Re, Rf, Rb1, Rd, Rc and internal standard (IS) were finally determined to be 120, 140, 140, 120, 140, 140, 140 and 60V, respectively, and EP 15, 15, 9, 15, 9, 9, 13, and 7V respe...

Embodiment 3

[0136] Embodiment 3 Pharmacodynamic research results and discussion

[0137] 1. Methodological validation

[0138] 1. Linear

[0139] Accurately absorb a certain amount of NO 3 － Standard stock solution, diluted with normal saline to a series of NO concentrations of 0, 2.5, 5.0, 10.0, 15.0, 20.0, 25.0, 30.0 and 40.0 μM 3 － The standard solution was subjected to HPLC-FLU analysis after being processed according to the method under item 2 of the fourth part of the above-mentioned embodiment 1. Will NO 3 － The peak area (y) of each standard solution concentration (x) and each reaction product NAT is carried out linear regression, obtains standard curve and is: y=240377.82x+123099.47, R 2 =0.9981, NO 3 － The physiological saline solution has a good linear relationship in the concentration range of 0-40.0μM.

[0140] 2. Precision and sample recovery

[0141] Accurately weigh 10 μL of the dialysate sample and treat it according to the method under item 2 of Part IV of Exa...

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Abstract

The invention relates to the technical field of medicines, and concretely relates to a blood dialysate detection method, and an application thereof in the pharmacokinetics-pharmacodynamics of a pulseactivating injection. The method comprises the following steps: preparing a conscious rat in-vivo microdialysis sampling device collected blood dialysate, analyzing the drug concentration of active ingredients in the blood dialysate by high performance liquid chromatography-triple quadrupole mass spectrography, and detecting the drug effect index NO in the blood dialysate by high performance liquid chromatography-fluorescence detection technique. A conscious rat in vivo microdialysis technique adopted in the invention overcomes the influences of animal anesthesia and blood loss on the pharmacokinetic and pharmacodynamic behaviors, is successfully used in the studying of the plasma concentration-time and drug effect-time relationships of the pulse activating injection against rat myocardialischemia, and can be used to establish a pharmacokinetic-pharmacodynamic combination model. A study result shows that when an appropriate blood endogenous biomarker is selected as a drug effect index, the conscious animal in vivo microdialysis sampling technique becomes an ideal tool for pharmacokinetic-pharmacodynamic combination studying.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular, it is an in vivo microdialysis sampling technique combined with a dialysate detection method for conscious rats, which is used to study isoproterenol (ISO)-induced myocardial ischemia. Pharmacokinetic-pharmacodynamic correlation after injection. Background technique [0002] Shengmai Injection is a compound preparation composed of red ginseng, Ophiopogon japonicus and Schisandra chinensis. It is widely used clinically to treat myocardial infarction, cardiogenic shock, septic shock and other diseases. It is a traditional Chinese medicine injection with effective curative effect. . Pharmacological studies have shown that Shengmai Injection has anti-oxidative protective activity against myocardial oxidative damage, increases coronary blood flow, reduces myocardial oxygen consumption, improves myocardial energy metabolism, increases myocardial contractility, reduces peripheral resist...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/88G01N30/06G01N30/74
CPCG01N30/06G01N30/74G01N30/88
Inventor 詹淑玉邵青丁宝月阮钰尔黄嬛黄雄刘国强吕晓庆姜宁华
Owner JIAXING UNIV
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