CN103417526A - Application of salvianolate in preparation of kidney protective agent drugs - Google Patents
Application of salvianolate in preparation of kidney protective agent drugs Download PDFInfo
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Abstract
The invention provides application of salvianolate in preparation of kidney protective agent drugs. A study on effects of injection-use salvianolate on acute myocardial perfusion in acute myocardial infarction direct PCI (percutaneous coronary intervention) and prognosis founds that: subjects using the injection-use salvianolate, compared with other group subjects, after use of a contrast agent, may not have severe kidney injuries, and the injection-use salvianolate has a kidney protective effect. The invention also provides the application of magnesium lithospermate B in preparation of the kidney protective agent drugs. Effects of the magnesium lithospermate B on kidney microcirculation and overall hemorheology are studied through use of spontaneously hypertensive rats. Experiments prove that the magnesium lithospermate B in physiological and pathological states both can dose-dependently improve kidney cortex microcirculation, and show that the kidney protective effect of the magnesium lithospermate B is realized through direct improvement of the kidney microcirculation, so that the salvianolate and the magnesium lithospermate B can be used for preparation of the drugs for the prevention and treatment of the kidney injures caused by the contrast agent. The application of the salvianolate in preparation of the kidney protective agent drugs has great clinical application value.
Description
Technical field
The present invention relates to medicine, be specifically related to the application in preparing kidney protective agent medicine of salvianolate and Radix Salviae Miltiorrhizae acetate magnesium.
Background technology
" Radix Salviae Miltiorrhizae for injection polyphenol hydrochlorate " is Chinese medicine two kind new medicines that Shanghai Pharmaceutical Inst., Chinese Academy of Sciences goes through research and development in 13 years, obtained the New Drug Certificate of raw material and preparation in May, 2005, by Shanghai Lvgu Pharmaceutical Co., Ltd, produced.Product was gone into operation and is gone on the market in 2006.Radix Salviae Miltiorrhizae for injection polyphenol hydrochlorate, for the patient of the direct PCI art of acute myocardial infarction, can reduce without flowing again, improves Myocardial Microcirculation.Improve recurrent angina pectoris, heart failure, death etc." Radix Salviae Miltiorrhizae for injection polyphenol hydrochlorate " research takes the lead in illustrating take the salvianolate that Radix Salviae Miltiorrhizae acetate magnesium is main component, is most important effective active composition in Radix Salviae Miltiorrhizae.This product effective ingredient is clear and definite, and content is high, and the total polyphenols acid content is nearly 100%, and Radix Salviae Miltiorrhizae acetate magnesium content reaches more than 80%, and other 20% components also all have clear and definite chemical constitution.As follows:
Rosmarinic acid sodium:
Alkannic acid magnesium:
The alkannic acid dipotassium:
Danshensu potassium:
Radix Salviae Miltiorrhizae acetic acid dipotassium:
Different Radix Salviae Miltiorrhizae acetic acid dipotassium:
Salvianolic acid G magnesium:
This product is usingd Radix Salviae Miltiorrhizae acetate magnesium in process of production as quality control standard, has used fingerprint pattern technology to carry out comprehensive control to the quality of medical material, crude drug and preparation.Simultaneously, preparation adopts the lyophilized powder technology, has avoided the unstability of this compounds, has guaranteed that the quality standard of product is significantly higher than same quasi-tradition red sage formulation.Result of study according to red sage root water soluble ingredient, the water solublity effective site Polyphenol Acids salt compounds of Radix Salviae Miltiorrhizae, wherein Radix Salviae Miltiorrhizae acetate magnesium is its most effective active component, this compounds all is present in raw medicinal herbs with the form of salt, wherein inorganic metal ion, especially magnesium ion are the important substance bases of its drug action.The demonstration of pharmacology activity research result, the pharmacologically active of salt is better than acid, and pharmacology's contribution of inorganic ions can not be ignored, so we are by product called after Radix Salviae Miltiorrhizae for injection polyphenol hydrochlorate, and quality control index is Radix Salviae Miltiorrhizae acetate magnesium.
The raw material of Radix Salviae Miltiorrhizae for injection polyphenol hydrochlorate is salvianolate, its main component is the Radix Salviae Miltiorrhizae acetate, its content has reached more than 80%, also contains in addition the homologue of the Radix Salviae Miltiorrhizae acetates such as Radix Arnebiae (Radix Lithospermi) hydrochlorate, Herba Rosmarini Officinalis hydrochlorate, and they are the Polyphenol Acids salt compounds.
China Patent No.: ZL98111076.2 has reported the preparation method of Radix Salviae Miltiorrhizae for injection polyphenol hydrochlorate: pulverize red rooted salvia, hot water extraction three times (4 times, 2 times of red rooted salvias and 2 times of weight), each 2 hours.Extracting solution merges, cooling, filters.Filtrate is adsorbed in the 1300-I macroporous adsorbent resin of 3 times of volumes, wash away sugar, protein and inorganic salt with 6 times of water gagings, remove again the poly phenolic acid of Radix Salviae Miltiorrhizae salt compounds of non-Radix Salviae Miltiorrhizae acetate with 6 times of amount 20% ethanol, finally with 3 times of amount 50% ethanol, wash out salvianolate.50% ethanol eluate of Radix Salviae Miltiorrhizae acetate is rich in collection, and after being evaporated to 1/10 crude drug amount, 90% ethanol precipitation, filter, filtrate decompression is concentrated into 1/20 crude drug amount, and 95% precipitation, filter, and filtrate decompression is concentrated, vacuum drying, pulverize, and packing, can obtain finished product.
Relevant Radix Salviae Miltiorrhizae acetate magnesium improves renal function, improves the existing research of effect of experimental renal failure.Current research shows, Radix Salviae Miltiorrhizae acetate magnesium is mainly by activating kallikrein, and the generation that improves PGE2, remove free radical to improve kidney recurrent state and renal function.But there is no so far the impact of report research Radix Salviae Miltiorrhizae acetate magnesium on renal microcirculation.Yet kidney is brought into play the effect at center in body water salt balance, microcirculation and an interior environment highly regulated and controled is most important for maintaining of best renal function.The inventor tests after deliberation and finds that Radix Salviae Miltiorrhizae acetate magnesium can improve renal microcirculation.The inventor uses spontaneous hypertensive rat to study Radix Salviae Miltiorrhizae acetate magnesium to renal microcirculation and the rheol impact of whole blood.Experimental result finds that Radix Salviae Miltiorrhizae acetate magnesium can promote the renal cortex Micro-perfusion in Graft After and whole recurrent state is not made significant difference first.In addition, recent research prompting oxygen-derived free radicals (as hypertension and diabetic nephropathy) in normal condition and Pathophysiology situation all participates in the regulation and control of renal cortex and medullary substance microvascular function.In the kidney blood capillary, oxygen-derived free radicals can cause vasoconstriction, mediates the vasoconstriction of other factors, regulates the effect of vasodilator drug (as NO).The concept that oxidative stress phenomenon in nephropathy has caused antioxidant to be applied to treatment as the kidney protective agent produces.(2011, Biochemical and Biophysical ResearchCommunications, The protective effect of magnesium lithospermate Bagainst glucose-induced intracellular oxidative damage), therefore, Radix Salviae Miltiorrhizae acetate magnesium is as a powerful antioxidant, can remove oxygen-derived free radicals, blocking-up O
2 --ONOO
---OH
--Cascade reaction, improve the amount usable of NO and improve renal microcirculation.This experiment confirms the raising renal cortex microcirculation of Radix Salviae Miltiorrhizae acetate magnesium equal dose dependent under physiology and pathological state, and the kidney protective effect of prompting Radix Salviae Miltiorrhizae acetate magnesium also directly improves renal microcirculation by it and realizes.Therefore, Radix Salviae Miltiorrhizae acetate magnesium can be used for preparing kidney protective agent medicine.
In addition; the inventor is in the clinical research of " impact of Radix Salviae Miltiorrhizae for injection Polyphenol Acids salt pair acute myocardial infarction direct PCI art heart muscle perfusion and prognosis "; be surprised to find that the experimenter who has used Radix Salviae Miltiorrhizae for injection polyphenol hydrochlorate does not cause the severe renal damage compared to other two groups of experimenters after having used contrast agent, and there is the kidney protective effect.Therefore Radix Salviae Miltiorrhizae for injection polyphenol hydrochlorate can be used for preparing kidney protective agent medicine.
Summary of the invention
Technical problem to be solved by this invention is to study Radix Salviae Miltiorrhizae for injection polyphenol hydrochlorate and Radix Salviae Miltiorrhizae acetate magnesium to the protective effect of kidney, designs new kidney protective agent medicine.
The invention provides the application of salvianolate in preparing kidney protective agent medicine.
The inventor carries out the clinical research of " impact of Radix Salviae Miltiorrhizae for injection Polyphenol Acids salt pair acute myocardial infarction direct PCI art heart muscle perfusion and prognosis ".Test lasts 4 years, 5 research centers, selected patient's 303 examples, the in test unexpected prevention and treatment of having found the injury of kidney that Radix Salviae Miltiorrhizae for injection Polyphenol Acids salt pair causes because of contrast agent.Before test comprises the serum creatinine treatment and after treatment (postoperative 7 days) become a full member (different); Serum creatinine judgement in postoperative 7 days turns exceptional value extremely; Serum creatinine judgement in postoperative 7 days normally turns exceptional value etc.Result shows, has used the experimenter of Radix Salviae Miltiorrhizae for injection polyphenol hydrochlorate to be compared to other group experimenters, after having used contrast agent, does not cause the severe renal damage, and has the kidney protective effect.Therefore, salvianolate can be used for preparing the prevention of the injury of kidney caused because of contrast agent and the medicine for the treatment of.
Another object of the present invention has been to provide the application of Radix Salviae Miltiorrhizae acetate magnesium in preparing kidney protective agent medicine.
In salvianolate, Radix Salviae Miltiorrhizae acetate magnesium is its most effective active component.The inventor uses spontaneous hypertensive rat to study Radix Salviae Miltiorrhizae acetate magnesium to renal microcirculation and the rheol impact of whole blood.Quiet notes gave the 60mg/kg salvianolic acid B magnesium after 15 minutes, and SHR rat renal artery blood flow is changed to 0.68 ± 2.21%; Renal vascular resistance is changed to 5.89 ± 2.12%, all only is slight variation; And the renal cortex Micro-perfusion in Graft After is changed to 65.85 ± 12.87%(P<0.001), be significantly increased.Experimental result finds that Radix Salviae Miltiorrhizae acetate magnesium can promote the renal cortex Micro-perfusion in Graft After and whole recurrent state is not made significant difference first.In addition, Radix Salviae Miltiorrhizae acetate magnesium, as a powerful antioxidant, can be removed oxygen-derived free radicals, blocking-up O
2 --ONOO-OH
-Cascade reaction, improve the amount usable of NO and improve renal microcirculation.This experiment confirms the raising renal cortex microcirculation of Radix Salviae Miltiorrhizae acetate magnesium equal dose dependent under physiology and pathological state, and the kidney protective effect of prompting Radix Salviae Miltiorrhizae acetate magnesium directly improves renal microcirculation by it and realizes.Therefore, Radix Salviae Miltiorrhizae acetate magnesium can be used for preparing the prevention of the injury of kidney caused because of contrast agent and the medicine for the treatment of.
The present invention is the new drug that prepared kidney protective agent drug provision, and larger clinical value is arranged.
The accompanying drawing explanation
Fig. 1 Radix Salviae Miltiorrhizae acetate magnesium is on the dynamic (dynamical) impact of spontaneous hypertensive rat renal blood flow.Three dosage groups of solvent control group and Radix Salviae Miltiorrhizae acetate magnesium were at every 45 minutes drug administration by injection.Numerical value means with mean ± standard error, n=9.(A) renal cortex microcirculatory perfusion; (B) renal blood flow; (C) renal vascular resistance.(zero) solvent control group; (■) Radix Salviae Miltiorrhizae acetate magnesium 10mg/kg group; (▲) Radix Salviae Miltiorrhizae acetate magnesium 30mg/kg group;
Radix Salviae Miltiorrhizae acetate magnesium 60mg/kg group.
AP ﹤ 0.05,
BP ﹤ 0.01 compares with the solvent control group;
aP<0.05,
bCompare with radix P<0.01.
Fig. 2 Radix Salviae Miltiorrhizae acetate magnesium is on the hemodynamic impact of spontaneous hypertensive rat system.Three dosage groups of solvent control group and Radix Salviae Miltiorrhizae acetate magnesium were at every 45 minutes drug administration by injection.Numerical value means with mean ± standard error, n=9.(A) heart rate; (B) mean arterial pressure; (C) left ventricular systolic pressure; (D) ventricular end diastolic pressure; (E) maximal ascending rate of internal pressure of left ventricle; (F) maximal descending rate of internal.(zero) solvent control group; (■) Radix Salviae Miltiorrhizae acetate magnesium 10mg/kg group; (▲) Radix Salviae Miltiorrhizae acetate magnesium 30mg/kg group;
Radix Salviae Miltiorrhizae acetate magnesium 60mg/kg group.
AP ﹤ 0.05,
BP ﹤ 0.01 compares (one-way ANOVA check) with the solvent control group;
aP<0.05,
b(paired t-test) compared with radix in P<0.01.
Fig. 3 Radix Salviae Miltiorrhizae acetate magnesium is on the rheol impact of whole blood
Fig. 4: the impact of Radix Salviae Miltiorrhizae acetate magnesium on the spontaneous hypertensive rat heart rate.Three dosage groups of solvent control group and Radix Salviae Miltiorrhizae acetate magnesium were at every 45 minutes drug administration by injection.Numerical value means with mean ± standard error, n=9.(zero) solvent control group; (■) Radix Salviae Miltiorrhizae acetate magnesium 10mg/kg group; (▲) Radix Salviae Miltiorrhizae acetate magnesium 30mg/kg group;
Radix Salviae Miltiorrhizae acetate magnesium 60mg/kg group.
AP ﹤ 0.05,
BP ﹤ 0.01 compares (one-way ANOVA check) with the solvent control group;
aP<0.05,
b(paired t-test) compared with radix in P<0.01.
Fig. 5: the impact of Radix Salviae Miltiorrhizae acetate magnesium on the spontaneous hypertensive rat mean arterial pressure.Three dosage groups of solvent control group and Radix Salviae Miltiorrhizae acetate magnesium were at every 45 minutes drug administration by injection.Numerical value means with mean ± standard error, n=9.(zero) solvent control group; (■) Radix Salviae Miltiorrhizae acetate magnesium 10mg/kg group; (▲) Radix Salviae Miltiorrhizae acetate magnesium 30mg/kg group;
Radix Salviae Miltiorrhizae acetate magnesium 60mg/kg group.
AP ﹤ 0.05,
BP ﹤ 0.01 compares (oneway ANOVA check) with the solvent control group;
aP<0.05,
b(paired t-test) compared with radix in P<0.01.
Fig. 6: the impact of Radix Salviae Miltiorrhizae acetate magnesium on the spontaneous hypertensive rat left ventricular systolic pressure.Three dosage groups of solvent control group and Radix Salviae Miltiorrhizae acetate magnesium were at every 45 minutes drug administration by injection.Numerical value means with mean ± standard error, n=9.(zero) solvent control group; (■) Radix Salviae Miltiorrhizae acetate magnesium 10mg/kg group; (▲) Radix Salviae Miltiorrhizae acetate magnesium 30mg/kg group;
Radix Salviae Miltiorrhizae acetate magnesium 60mg/kg group.
AP ﹤ 0.05,
BP ﹤ 0.01 compares (one-wayANOVA check) with the solvent control group;
aP<0.05,
b(paired t-test) compared with radix in P<0.01.
Fig. 7: the impact of Radix Salviae Miltiorrhizae acetate magnesium on the spontaneous hypertensive rat ventricular end diastolic pressure.Three dosage groups of solvent control group and Radix Salviae Miltiorrhizae acetate magnesium were at every 45 minutes drug administration by injection.Numerical value means with mean ± standard error, n=9.(zero) solvent control group; (■) Radix Salviae Miltiorrhizae acetate magnesium 10mg/kg group; (▲) Radix Salviae Miltiorrhizae acetate magnesium 30mg/kg group;
Radix Salviae Miltiorrhizae acetate magnesium 60mg/kg group.
AP ﹤ 0.05,
BP ﹤ 0.01 compares (one-way ANOVA check) with the solvent control group;
aP<0.05,
b(paired t-test) compared with radix in P<0.01.
Fig. 8: the impact of Radix Salviae Miltiorrhizae acetate magnesium on the spontaneous hypertensive rat maximal ascending rate of internal pressure of left ventricle.Three dosage groups of solvent control group and Radix Salviae Miltiorrhizae acetate magnesium were at every 45 minutes drug administration by injection.Numerical value means with mean ± standard error, n=9.(zero) solvent control group; (■) Radix Salviae Miltiorrhizae acetate magnesium 10mg/kg group; (▲) Radix Salviae Miltiorrhizae acetate magnesium 30mg/kg group;
Radix Salviae Miltiorrhizae acetate magnesium 60mg/kg group.
AP ﹤ 0.05,
BP ﹤ 0.01 compares (one-way ANOVA check) with the solvent control group;
aP<0.05,
b(paired t-test) compared with radix in P<0.01.
The specific embodiment
Embodiment 1
Radix Salviae Miltiorrhizae acetate magnesium is on the microcirculatory impact of SHR renal cortex of rats
Kidney plays a decisive role in maintaining body water salt balance.Microcirculation and an interior environment highly regulated and controled is most important for maintaining of best renal function.The dynamic response ability that renal microcirculation needs an inherence is to maintain environment in suitable kidney.This experimentation salvianolic acid B magnesium is on Hypertensive Rats renal microcirculation and hemorheological impact.
1. materials and methods
1.1 reagent and medicine
Radix Salviae Miltiorrhizae acetate magnesium (Magnesiumlithospermate B, MLB; Purity is 95%) by Shanghai Lvgu Pharmaceutical Co., Ltd, produced, be light brown.With the normal saline preparation, the 5ml normal saline is injected to sucking-off after dilution in cillin bottle before use, then the liquid after diluting injects the 250ml normal saline.Reagent is commercially available analytical pure product.
Transonic T 206 ultrasonic dopplers are purchased from U.S. Transonic Systems Inc. (Transpac, North Chicago, Illinois, USA), and supporting each model is popped one's head in and DATA TAQ data analysis system.Polygragh System eight lead systems are purchased from Nihon Kohden(Japan), MacLab/8S is purchased from AnalogDigital Instruments, Pty Ltd(CastleHill, NSW, Australia).The MLD-1 laser Doppler system is purchased from Nankai University, data analysis software (MATLAB, U.S. MathWorks company produces).
1.2 laboratory animal
Test with male spontaneous hypertensive rat (SHR, body weight 401.4 ± 4.7g).Rat is fed with normal feedstuff and water.
1.3 operation technique and drug treating
Pentobarbital sodium anesthesia (60mg/kg for SHR, ip), rat anesthesia is placed on hot plate to maintain body temperature, separate the parallel arterial cannulation of femoral artery, arterial cannulation (PE30) be connected in pressure transducer (Transpac of Transonic system, North Chicago, Illinois, USA) be connected and measure arterial pressure with real-time continuous.Carry out the left ventricular cannulation art to detect whole loop condition, pressure transducer (P23XL, Statham, Nihon Kohden, Japan) be connected to Polygraph System(polygraph system) (NihonKohden, Japan) and be connected to that computer data acquiring processing system (MacLab/8S, Analog DigitalInstruments, Australia) is analyzed, record.Open abdominal cavity, expose left kidney, ultrasonic Doppler probe (1RB, Transonic Systems Inc.) is hooked around the renal artery blood vessel and measures renal artery blood flow with real-time continuous.DOPPLER ULTRASOUND SIGNAL reaches ultrasonic Doppler blood flowmeter (T206, Transonic SystemsInc.) system log (SYSLOG), preservation, and is analyzed with DATAQ software (WinDaq/Lite/Pro/Pro+ U.S. DATAQ company).This ultrasonic Doppler blood flowmeter is measured absolute vascular flow (ml/min), and precision is ± 5%.With micromanipulator (Narishige scientific instrument Lab., Japan) the fixed laser doppler transducer is in the renal cortex surface, and adjust probe orientation and with the relative position on renal cortex surface, make the laser Doppler signal continous-stable.These laser Doppler signals are by reaching another computer system analysis, record after laser Doppler flowmetry (LDM, NankaiUniversity, China) processing and amplifying.
Each parameter is all got the meansigma methods in half a minute to one minute.Renal vascular resistance measures divided by corresponding renal artery blood flow with mean arterial pressure.
At least stablize after operation 30 minutes, start administration after parameters be stable: successively every 45 minutes respectively intravenous injection give normal saline and salvianolic acid B magnesium 10,30,60mg/kg.
1.4 statistical analysis
Data mean with means ± SEM standard error, and its significance,statistical is with student t test check analysis.Think that significant difference is arranged when P<0.05.
2. result
2.1 Radix Salviae Miltiorrhizae acetate magnesium is on renal microcirculation and the hemorheological impact of kidney
Renal cortex microcirculation and hemorheology parameters basic value zero difference (Fig. 1) when experiment starts.Intravenous injection Radix Salviae Miltiorrhizae acetate magnesium or normal saline (blank) are on renal artery blood flow all without impact, but quiet notes 30,60mg/kg Radix Salviae Miltiorrhizae acetate magnesium slightly improve the renal vascular resistance (Fig. 2) of spontaneous hypertensive rat (SHR).With these slight changes, form distinct contrast, each dosage Radix Salviae Miltiorrhizae acetate magnesium of quiet notes renal cortex microcirculatory perfusion that is significantly increased, and be dosage correlation (Fig. 1, table 1,2).The renal cortex Micro-perfusion in Graft After raises fast after quiet notes give Radix Salviae Miltiorrhizae acetate magnesium, at 15 minutes internal effects, reaches maximum, in 45 minutes, gets back to baseline.
Quiet notes gave the 60mg/kg Radix Salviae Miltiorrhizae acetate magnesium after 15 minutes, and SHR rat renal artery blood flow is changed to 0.68 ± 2.21%; Renal vascular resistance is changed to 5.89 ± 2.12%, all only is slight variation; And the renal cortex Micro-perfusion in Graft After is changed to 65.85 ± 12.87%(P<0.001), be significantly increased.The impact of table 1 salvianolic acid B magnesium on the renal vascular resistance of spontaneous hypertensive rat, unit: BPU. (n=9).
Result means with standard error. with baseline, compares
*P<0.05,
*P<0.01; With the blank group, compare
Table 2 is used Radix Salviae Miltiorrhizae acetate magnesium kidney of rats artery blood flow variation (n=9) after 15 minutes.
Result means with standard error; N>=8. compare with baseline
*P<0.05, and the blank group is relatively
*P<0.01;
2.2 Radix Salviae Miltiorrhizae acetate magnesium is on the rheol impact of whole blood
The whole blood equal zero difference of each parameter of rheology (Fig. 3) when experiment starts.Quiet notes normal saline on each parameter all without the impact; And quiet notes Radix Salviae Miltiorrhizae acetate magnesium affects some parameters to some extent at some time points, but not free dependency or dose dependent.After the quiet notes of SHR 60mg/kg Radix Salviae Miltiorrhizae acetate magnesium, mean arterial pressure is changed to 6.4 ± 1.5%(P<0.01, vs baseline), changes in heart rate is 0.8 ± 1.5%, LVSP is changed to 7.1 ± 2.8%(P<0.05, vs baseline), LVEDP is changed to 33.3 ± 14.7%(P>0.05, vs baseline) ,+dP/d
TmaxBe changed to 8.7 ± 2.2%(P<0.05, vs baseline), and-dP/d
TmaxBe changed to 9.4 ± 3.5%(P<0.01, vs baseline) slight rising arranged.
3. discuss
Kidney is brought into play the effect at center in body water salt balance, and microcirculation and an interior environment highly regulated and controled is most important for maintaining of best renal function.The effect that Radix Salviae Miltiorrhizae acetate magnesium improves renal function, improve experimental renal failure is studied widely.Research in the past shows, Radix Salviae Miltiorrhizae acetate magnesium is mainly by activating kallikrein, and the generation that improves PGE2, remove free radical to improve kidney recurrent state and renal function.But there is no so far the impact of report research Radix Salviae Miltiorrhizae acetate magnesium on renal microcirculation.We use spontaneous hypertensive rat to study Radix Salviae Miltiorrhizae acetate magnesium to renal microcirculation and the rheol impact of whole blood.Experimental result finds that Radix Salviae Miltiorrhizae acetate magnesium can promote the renal cortex Micro-perfusion in Graft After and whole recurrent state is not made significant difference first.
Nearest research prompting oxygen-derived free radicals (as hypertension and diabetic nephropathy) in normal condition and Pathophysiology situation all participates in the regulation and control of renal cortex and medullary substance microvascular function.In the kidney blood capillary, oxygen-derived free radicals can cause vasoconstriction, mediates the vasoconstriction of other factors, regulates the effect of vasodilator drug (as NO).The concept that oxidative stress phenomenon in nephropathy has caused antioxidant to be applied to treatment as the kidney protective agent produces.The inventor thinks, Radix Salviae Miltiorrhizae acetate magnesium, as a powerful antioxidant, can be removed oxygen-derived free radicals, blocking-up O
2 --ONOO
---OH
--Cascade reaction, improve the amount usable of NO and improve renal microcirculation.This experiment confirms the raising renal cortex microcirculation of Radix Salviae Miltiorrhizae acetate magnesium equal dose dependent under physiology and pathological state, and the kidney protective effect of prompting Radix Salviae Miltiorrhizae acetate magnesium also may partly directly improve renal microcirculation by it and realize.
Embodiment 4
The prevention and treatment of the injury of kidney that Radix Salviae Miltiorrhizae for injection Polyphenol Acids salt pair contrast agent causes
Radix Salviae Miltiorrhizae for injection polyphenol hydrochlorate is to be produced by Shanghai Lvgu Pharmaceutical Co., Ltd, and its specification is respectively every bottled 50mg(containing Radix Salviae Miltiorrhizae acetate magnesium 40mg), every bottled 100mg(is containing Radix Salviae Miltiorrhizae acetate magnesium 80mg), every bottled 200mg(is containing Radix Salviae Miltiorrhizae acetate magnesium 160mg).Operative norm is the standard YBZ09012005-2010Z of State Food and Drug Administration.
Result data is as follows:
Before table 3 serum creatinine treatment with treatment after (postoperative 7 days) (different) list of becoming a full member
Table 4 serum creatinine judgement in postoperative 7 days turns exceptional value (μ mol/L) list extremely
Annotate: " abnormal-" for extremely without clinical meaning; " abnormal+" is for extremely there being clinical meaning
Table three 5 serum creatinine judgement in postoperative 7 days normally turns exceptional value (μ mol/L) list
Annotate: " abnormal-" for extremely without clinical meaning; " abnormal+" is for extremely there being clinical meaning
According to table 4,5 results show, A group (Radix Salviae Miltiorrhizae for injection polyphenol hydrochlorate group) experimenter gets involved accepting the PCI(percutaneous coronary) after the treatment operation, abnormal from normally becoming without 1 routine experimenter's serum creatinine value, there are 3 routine experimenter's serum creatinine values to take a turn for the better to some extent on original abnormal basis, there are 2 routine experimenter's serum creatinine values to increase the weight of to some extent on original abnormal basis, wherein only have 1 routine amplification to surpass 10%; B group (tirofiban group) experimenter is after accepting the PCI operation, there are 3 routine experimenter's serum creatinine values abnormal from normally becoming, there is 1 routine experimenter's serum creatinine value to take a turn for the better to some extent on original abnormal basis, have 2 routine experimenter's serum creatinine values to increase the weight of to some extent on original abnormal basis, wherein 2 routine amplification have all surpassed 10%; C group (blank group) experimenter is after accepting the PCI operation, there are 3 routine experimenter's serum creatinine values abnormal from normally becoming, there are 3 routine experimenter's serum creatinine values to take a turn for the better to some extent on original abnormal basis, have 3 routine experimenter's serum creatinine values to increase the weight of to some extent on original abnormal basis, wherein 2 routine amplification have surpassed 25%.Comprehensive above-mentioned data can be found out, have used the experimenter of Radix Salviae Miltiorrhizae for injection polyphenol hydrochlorate not cause the severe renal damage compared to other two groups of experimenters after having used contrast agent, and have had the kidney protective effect.
Claims (5)
1. the application of salvianolate in preparing kidney protective agent medicine.
2. application according to claim 1, is characterized in that, the described medicine that is applied as salvianolate preparation prevention and treats the injury of kidney caused because of contrast agent.
3. application according to claim 1 and 2, it is characterized in that, Radix Salviae Miltiorrhizae acetate magnesium content in described salvianolate reaches more than 80%, and other 20% components are that rosmarinic acid sodium, alkannic acid magnesium, alkannic acid dipotassium, danshensu potassium, Radix Salviae Miltiorrhizae acetic acid dipotassium, different Radix Salviae Miltiorrhizae acetic acid dipotassium, salvianolic acid G magnesium are as follows:
Radix Salviae Miltiorrhizae acetate magnesium:
Rosmarinic acid sodium:
Alkannic acid magnesium:
The alkannic acid dipotassium:
Danshensu potassium:
Radix Salviae Miltiorrhizae acetic acid dipotassium:
Different Radix Salviae Miltiorrhizae acetic acid dipotassium:
Salvianolic acid G magnesium:
4. the application of Radix Salviae Miltiorrhizae acetate magnesium in preparing kidney protective agent medicine.
5. application according to claim 4, is characterized in that, the described medicine that is applied as Radix Salviae Miltiorrhizae acetate magnesium preparation prevention and treats the injury of kidney caused because of contrast agent.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104974119A (en) * | 2014-04-01 | 2015-10-14 | 中国科学院上海药物研究所 | High-purity magnesium salvianolate B and preparation method thereof |
| CN106309414A (en) * | 2016-08-23 | 2017-01-11 | 安徽医科大学 | Application of protocatechuic aldehyde in drug for treating acute kidney injury and prepared drug for treating acute kidney injury |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104974119A (en) * | 2014-04-01 | 2015-10-14 | 中国科学院上海药物研究所 | High-purity magnesium salvianolate B and preparation method thereof |
| CN104974119B (en) * | 2014-04-01 | 2018-10-19 | 中国科学院上海药物研究所 | A kind of high-purity danshinolic acid B magnesium and preparation method thereof |
| CN106309414A (en) * | 2016-08-23 | 2017-01-11 | 安徽医科大学 | Application of protocatechuic aldehyde in drug for treating acute kidney injury and prepared drug for treating acute kidney injury |
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