CN101721466B - Quality control method for salvianolic acid injection - Google Patents
Quality control method for salvianolic acid injection Download PDFInfo
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- CN101721466B CN101721466B CN 200810152399 CN200810152399A CN101721466B CN 101721466 B CN101721466 B CN 101721466B CN 200810152399 CN200810152399 CN 200810152399 CN 200810152399 A CN200810152399 A CN 200810152399A CN 101721466 B CN101721466 B CN 101721466B
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Abstract
The invention discloses a quality control method for salvianolic acid injection, which uses the medicinal effect result of an observed sample as an index, and specifically uses the influence of the observed sample on the aggregation function of platelets in a tested animal as an index. The method of the invention conveniently and effectively realizes quality control on the salvianolic acid injection, integrally characterizes the quality of the salvianolic acid injection, is simple and feasible, and has accurate and reliable results.
Description
Technical field
The present invention relates to the traditional Chinese medicine quality control field, be specifically related to a kind of method of quality control of salvianolic acid injection.
Background technology
The red sage root is the dry rhizome of labiate red sage root Salvia miltiorrhiza Bunge, to use in China's traditional medicine the earliest and one of medicine the most widely, clinical practice and modern medicine study through long-term have had comprehensive understanding to its clinical effectiveness, pharmacological action.Traditional Chinese medicine theory thinks that the red sage root can promoting blood circulation; Menstruction regulating and pain relieving; Nourishing blood and tranquilization; The cool blood carbuncle that disappears cures mainly menoxenia; Dysmenorrhoea; Through closing; The stasis of blood stagnated and suffered from abdominal pain postpartum; Trusted subordinate's pain; Lumps in the chest and abdomen; Hot numbness swells and ache; Traumatic injury; Heat enters ying blood; Have the fidgets; Vexed insomnia; The carbuncle pyogenic infections from tumour or sore.Modern pharmacology studies show that; the effect such as the red sage root has Cerebral ischemia protection, improves coronary flow and microcirculation, promotion organization restoration, platelet aggregation-against, antitumor, anti-inflammatory is antibacterial is mainly used in the diseases such as coronary heart disease coronary heart disease, acute myocardial infarction, cerebral infarction, chronic hepatitis clinically.Recent study also finds, the red sage root also has certain curative effect to illnesss such as insomnia, chronic hepatitis, tumour and digestive tract ulcers.(Chinese patent, application number 200710111232.4, applying date 2007.6.18).
Effective constituent in the red sage root comprises liposoluble constituent and water soluble ingredient.Liposoluble constituent is the quinones take tanshinone as representative, has good antiinflammatory action; Water-soluble components mainly contains danshensu, protocatechualdehyde, Rosmarinic acid, alkannic acid, caffeic acid, danshinolic acid (A, B), is generically and collectively referred to as total phenolic acid, also has report to be called polydanshinolate or salvia root polyphenol acid.Salvianolic acid has the effects such as obvious antithrombotic formation, molten fibre and anti peroxidation of lipid, is the effective constituent of the angiocardiopathies such as treatment myocardial ischemia, angina pectoris, myocardial infarction, and wherein the content of tanshin polyphenolic acid B is the highest, and is its main active component.(separation purifying technique of total phenolic acid research in the red sage root, Yang Xiaoning etc., Chinese herbal medicine, 2007,38 (6): 843-846).
Salvianolic acid injection comprises parenteral solution, powder-injection and the transfusion etc. of salvianolic acid, and [function cures mainly] is: promoting blood circulation and removing obstruction in channels.Be used for apoplexy apoplex involving the channels and collaterals obstruction of collaterals by blood stasis disease and fall ill 1 week to 6 month, disease is seen hemiplegia, and dispute is crooked, and tongue says by force stuttering or in silence, Atherosclerosis and thrombosis and cerebral infarction is seen above-mentioned disease person.Be widely used in clinically treatment and the prevention of the cardiovascular and cerebrovascular diseases such as angina pectoris, myocardial infarction.Index in the salvianolic acid injection quality standard mostly is the Biological indicators of physical and chemical inspection index and Partial security (thermal source etc.).Salvianolic acid injection effective constituent (salvianolic acid) is carried out the important content that quantitative test is its quality standard, safe and effective special significance arranged to what guarantee clinical application.But the salvianolic acid injection complicated component, not only difficulty is large to measure each single component, and is not enough to reflect the inherent quality of salvianolic acid injection comprehensively.
Summary of the invention
In order to address the above problem, the present invention realizes the salvianolic acid injection quality control easily and effectively by the Biological indicators (namely observing the drug effect result of sample) of check sample validity.
Method of quality control of the present invention realizes for index platelet aggregation impact in the experimental animal body by observing sample, preferably take comparative sample with contrast L-Arginine in the experimental animal body as index.
Method of quality control of the present invention is achieved through the following technical solutions:
(1) take physiological saline or glucose injection or water for injection as contrast;
(2) drug administration by injection is all adopted in sample and contrast;
(3) working sample and the blood platelet MA of contrast to animal used as test;
(4) calculate L-Arginine according to each group blood platelet MA;
(5) result judges: compare (t check) between sample sets and control group blood platelet MA are organized, significant difference should be arranged.
Described step (3) adopts platelet aggregation instrument working sample and the blood platelet MA of contrast to animal used as test by turbidimetry.Preferred steps is tested and the control-animal blood sample for getting respectively, and anti-freezing is centrifugal, makes respectively platelet rich plasma (PRP) and platelet poor plasma (PPP), and incubation adds the aggregation inducing agent among the PRP, record blood platelet MA.
More preferably comprise the steps: to get respectively test and control-animal blood sample, put in the silication centrifuge tube, with 3.8% sodium citrate solution 9:1 anti-freezing, centrifugal 5 minutes of 1000rpm, make platelet rich plasma (PRP), with 2000rpm centrifugal 10 minutes, make platelet poor plasma (PPP), by turbidimetry, adopt platelet aggregation instrument to measure hematoblastic MA.Put in the mensuration pipe with 0.2mlPRP, 0.2mlPPP puts opposite side and measures (control tube) correction 100% transmitance value in the pipe.Incubation 5 minutes is put 0.2mlPRP and is measured aggregation inducing agent (ADP disodium salt) the 10 μ l that add 200 μ mol in the pipe, records immediately blood platelet MA in 5 minutes.
In the described step (4), the L-Arginine computing method are: L-Arginine (%)=(control group aggregation rate-administration group aggregation rate)/control group aggregation rate.
At present having separated the salvianolic acid compound that obtains has 18 kinds, also has danshinolic acid F, G, H, I, J and the isophenol acid C of salviandic acid A, B, C, D, E, alkannic acid, Rosmarinic acid, methyl rosmarinate and the new depside of genus of depside except more common protocatechualdehyde, protocatechuic acid, caffeic acid and danshensu.This shows danshinolic acid constituents complex.The complicated component of Chinese medicine, because the difference of technological reason and the medicinal material place of production, quality, stable and each component ratio of chemical composition composition stablizes between very difficult each batch of assurance.The basis of curative effect of medication is its chemical composition, the unstable product curative effect that directly has influence on of chemical composition.Traditional traditional Chinese medicine quality standard is simple a kind of (minority is measured several) component content of measuring wherein just, compositions all in the Chinese medicine can not be measured, moreover because the restriction of prior art, the composition of assay not necessarily plays the principal ingredient of curative effect.By above reason, assay can not effectively be controlled the drug effect of Chinese medicine.The present invention is by the Biological indicators (namely observing the drug effect result of sample) of check sample validity, biologically active by working sample is examined the quality of the production, realized easily and effectively the salvianolic acid injection quality control, characterized on the whole the quality of salvianolic acid injection, simple, the result accurately and reliably.
Salvianolic acid is the general name of this area, also has the names such as salvia root polyphenol acid, polydanshinolate in the prior art, and essence is identical with salvianolic acid.
Embodiment
Below by concrete embodiment method of quality control of the present invention is further specified, but not as limitation of the present invention.
Embodiment 1
1 test sample and reagent
1.1 total salvianolic acid injection Tianjin TianShiLi ZhiJiao Medicine Co., Ltd 20060601,20060801,20061101 batches.
1.2 aggregation inducing agent: 5 adenosine diphosphate disodium salts (ADP): specification: 0.1g: bottle, lot number: A2754, U.S. SIGMA company produces.
1.3 adrenalin hydrochloride: specification: 1mg/ml/ props up, lot number: 0608181, and Tianjin gold credit amino acid company limited.
1.4 collagen: specification 1g/ bottle, lot number: 124H7060, U.S. SIGMA company produces.
1.50.9% sodium chloride injection specification: the 500ml/ bottle, lot number: 6180C is produced by Otsuka Pharmaceutical (China) Co., Ltd..
2 instruments
BS-634 platelet aggregation instrument, biochemical instrument factory in Beijing produces.
3 animals
3.1 mouse, strain: CD-1 (ICR), body weight 26-28 gram, male, the SPF level.Dimension tonneau China experimental animal technology company limited provides credit number by Beijing: SCXK (capital)-2002-0003.
3.2 rat: strain: SD, body weight 220-240 grams, male, the SPF level.Dimension tonneau China experimental animal technology company limited provides credit number by Beijing: SCXK (capital)-2002-0003.
Test method and result:
Get 40 of SD rats, male, be divided into 4 groups, establish control group, give equivalent physiological saline, test group gives total salvianolic acid injection 20060601,20060801, the 20061101 crowdes of 39.9mg/ml (be equivalent to day for human beings quantity 30 times).Administration volume 10ml/kg, injection speed are 2ml/min, and each organizes rat all from tail vein injection successive administration 3 days, measures fasting the previous day, after the last administration 20 minutes, and rats by intraperitoneal injection 20% urethane 1g/5ml/kg anesthesia.Dorsal position is fixed.Take a blood sample from the rat abdominal aorta with the silication syringe, put in the silication centrifuge tube, with 3.8% sodium citrate solution 9:1 anti-freezing, centrifugal 5 minutes of 1000rpm, make platelet rich plasma (PRP), with 2000rpm centrifugal 10 minutes, make platelet poor plasma (PPP), by turbidimetry, adopt BS-634 type platelet aggregation instrument to measure the blood platelet MA, every rat is got PRP0.2ml and places the mensuration pipe, places another to measure pipe (control tube) 0.2mlPPP and proofreaies and correct 100% transmitance value.Incubation 5 minutes is put 0.2mlPRP and is measured adding 200 μ molADP solution 10 μ l in the pipe, records immediately blood platelet MA in 5 minutes.Between organizing with the blood platelet MA of each group relatively (t check), and calculate L-Arginine.The results are shown in following table:
L-Arginine (%)=(control group aggregation rate-administration group aggregation rate)/control group aggregation rate
The result: compare with control group, sample sets has significant difference.Up to specification.
Those skilled in the art can be applied to said method other forms of salvianolic acid injection in conjunction with the general knowledge of this area, such as powder-injection, transfusion etc., and need not creatively work of cost.
Method of quality control of the present invention can expand to all blood platelet inhibiting rates in the body and be medicine and the formulation of pharmacodynamics index, such as the granule of salvianolic acid, tablet, capsule etc., all drops within protection scope of the present invention.
The preparation of embodiment 2 salvianolic acid parenteral solutions
One, raw material preparation
Salvia piece 1000 grams, the 6000ml water boil extracts three times, each 0.5 hour.Merge extract, filter, filtrate restrains the AB-8 macroporous resin column, the flushing of 10000ml water, 50% ethanol 10000ml wash-out by 1000 after transferring ph value 3.5 with 10% hydrochloric acid, eluent is concentrated to without alcohol, concentrate is by 500 gram polyamide, 12000ml30% alcohol flushing, 12000ml95% ethanol elution, concentrated ethanol eluate, spray drying.Get extract 28 grams, content of danshinolic acid B 59%, salvianolic acid 83.1%.
Two, preparation prescription forms and preparation
Salvianolic acid 100g
Sweet mellow wine 100g
Water for injection adds to 2500ml
Get salvianolic acid, inject water 1000ml and make in right amount dissolving, stir evenly; Other gets sweet mellow wine, injects water 500ml and makes dissolving, adds in the mentioned solution, stirs evenly 0.5 gram activated charcoal insulated and stirred 20 minutes, filter, it is 4.5～5.0 that filtrate is regulated the pH value, injects water to 2500ml, aseptic filtration, packing, freeze drying is made 1000, and be get final product.
Claims (3)
1. the detection method of a salvianolic acid injection L-Arginine is characterized in that may further comprise the steps:
(1) take physiological saline or glucose injection or water for injection as contrast;
(2) drug administration by injection is all adopted in sample and contrast;
(3) get respectively test and control-animal blood sample, put in the silication centrifuge tube, with the anti-freezing in 9: 1 of 3.8% sodium citrate solution, centrifugal 5 minutes of 1000rpm, make platelet rich plasma, with 2000rpm centrifugal 10 minutes, make platelet poor plasma, by turbidimetry, adopt platelet aggregation instrument to measure hematoblastic MA, put with the 0.2ml platelet rich plasma and measure in the pipe, 0.2ml platelet poor plasma is put opposite side and is measured correction 100% transmitance value in the pipe, incubation 5 minutes is put the 0.2ml platelet rich plasma and is measured the aggregation inducing agent 10 μ l that add 200 μ mol in the pipe, records immediately blood platelet MA in 5 minutes;
(4) calculate L-Arginine according to each group blood platelet MA, computing method are: L-Arginine (%)=(control group aggregation rate-administration group aggregation rate)/control group aggregation rate;
(5) result judges: relatively, significant difference should be arranged between sample sets and control group blood platelet MA are organized;
Described sample prepares by following method:
Raw material preparation: salvia piece 1000 grams, the 6000ml water boil extracts three times, each 0.5 hour, merge extract, filter, filtrate restrains the AB-8 macroporous resin column, the flushing of 10000ml water, 50% ethanol 10000ml wash-out by 1000 after transferring ph value 3.5 with 10% hydrochloric acid, eluent is concentrated to without alcohol, concentrate is by 500 gram polyamide, 12000ml30% alcohol flushing, 12000ml95% ethanol elution, concentrated ethanol eluate, spray drying gets extract 28 grams, content of danshinolic acid B 59%, salvianolic acid 83.1%; Preparation prescription forms and preparation: salvianolic acid 100g, sweet mellow wine 100g, water for injection add to 2500ml, get salvianolic acid, inject water 1000ml and make in right amount dissolving, stir evenly; Other gets sweet mellow wine, injects water 500ml and makes dissolving, adds in the mentioned solution, stirs evenly 0.5 gram activated charcoal insulated and stirred 20 minutes, filter, it is 4.5～5.0 that filtrate is regulated the pH value, injects water to 2500ml, aseptic filtration, packing, freeze drying is made 1000, and be get final product.
2. detection method claimed in claim 1 is characterized in that the middle sample dosage of described step (2) is equivalent to 30 times of day for human beings quantity.
3. detection method claimed in claim 1 is characterized in that described step (2) is successive administration 3 days.
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| CN103919759B (en) * | 2014-04-06 | 2016-03-16 | 吴静 | A kind of containing danshensu sodium, the pharmaceutical composition of salvia miltiorrhiza tanshinoate F and preparation thereof |
| CN105588885B (en) * | 2014-10-24 | 2019-12-31 | 天津天士力之骄药业有限公司 | Salvianolic acid extract fingerprint spectrum and content determination method of related components |
| CN105548509B (en) * | 2016-01-26 | 2018-04-24 | 中国人民解放军新疆军区联勤部药品仪器检验所 | The detection method of drug quality |
| CN106093223B (en) * | 2016-05-31 | 2018-06-15 | 天津中医药大学 | A kind of research method of Danshen injection polyphenol absolute acid stability and its analysis method of degradation pathway |
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| CN101264270A (en) * | 2008-04-25 | 2008-09-17 | 北京和润创新医药科技发展有限公司 | Chinese medicinal composition for treating endometriosis symptoms and preparation thereof |
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