CN104013613A - Application of vitamin E in puerarin injection - Google Patents
Application of vitamin E in puerarin injection Download PDFInfo
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- CN104013613A CN104013613A CN201410248191.3A CN201410248191A CN104013613A CN 104013613 A CN104013613 A CN 104013613A CN 201410248191 A CN201410248191 A CN 201410248191A CN 104013613 A CN104013613 A CN 104013613A
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Abstract
The invention relates to an application of vitamin E in a puerarin injection. The vitamin E and the puerarin are combined to prepare the injection containing the puerarin, or the vitamin E injection and the puerarin injection are combined to use, so that the poor reaction of adventitious hemolysis of the puerarin injection is effectively overcome, and the safety of the puerarin injection drug delivery is improved.
Description
Technical field
The present invention relates to the new medical use of vitamin E, be specifically related to the application in puerarin injection.
Background technology
Vitamin E has another name called tocopherol, Vitamin E.Vitamin E has tetra-kinds of a, b, r, g, active the strongest with a, accounts for tocopherol activity 90%.Vitamin E has anti-aging effects.Heavy dose of application vitamin E can be treated peptic ulcer.Promote wound healing, there is antiinflammatory action.Prevent and treat hemolytic anemia of newborn.Enhance hepatocyte function of detoxification (seeing the novel clinical use > > of the < < vitamin E that Jie newly writes, capital medicine, 2003,9:32 page).Vitamin E also has antitumaous effect (the novel clinical use > > of the < < vitamin E that the happiness of Jian Ren state, Guo Qiling, Yuan Yin, Li Ying, Guo Shaohua write, Chinese Rural medicine, 1995,5:228 page).In diabetes, vitamin E can improve the sensitivity of diabetics to insulin by removing free radical, reduces blood lipid level, suppresses blood and fastens plain generation, controls diabetes.Vitamin E can be treated coronary heart disease, suppresses LDL oxidation, atherosclerosis and hypertension.Treatment intractable epilepsy, thyroid adenoma, viral hepatitis (are shown in that Shen Weikang, king increase the novel clinical use > > that dissolves the < < vitamin E of writing, Shandong medicine, 1996,36 (1): 56-57 page).Vitamin E treatment unstable angina pectoris, treatment primary nephrotic syndrome high blood coagulation sexual orientation, hemolytic uremic syndrome, prevention, delay Parkinson's disease and (see the novel clinical use > > of the < < vitamin E that Wei Xulan, Liu Yuan silks are write, modern diagnosis and treatment, 1991,2 (1): 59-61 page).The clinical ancillary drug that can be used as of vitamin E is for neural, muscle illness, encephalitis, cerebral edema etc. is also contributed to improve symptom and shortens the course of disease and (see clinical practice and the points for attention > > of the < < vitamin E that Hu Yanshui, Sun Lijing, Bao Yanfen write, medicine Leader, 2005,24 (3): 252-253 page).Vitamin E can also treat alzheimer disease, amnesia, delay alzheimer disease, improves memory, muscle fatigue is ached, alleviated to treatment shoulder, eliminates stress.Prevention platelet aggregation, reduce hemopexis effect, can prevent thrombophlebitis, thrombosis, myocardial infarction, prevention apoplexy (is shown in the clinical application > > of the < < vitamin E that Wu Huping, Zhang Fangfang write, Chinese Rural medical magazine, 2003,10 (10): 45-46 page).
Puerarin is the monomer-isoflavone compounds extracting from the dry root of legume pueraria lobata, 4 ', and 7 one dihydroxy-8-β-D glucone isoflavone.Be widely used in clinically the treatment of cardiovascular disease.Being applied at present the clinical pharmaceutical preparation that contains puerarin is mainly injection.Along with being widely used of puerarin, the report of relevant puerarin untoward reaction is also more and more in recent years, causes the world of medicine's extensive concern.By analyzing nearly 20 years adverse reaction of tcm, puerarin injection ranks the 18th.The untoward reaction of puerarin injection had once been circulated a notice of at national drug adverse reaction monitoring center in phase < < adverse drug reaction communication > > January the 3rd in 2003.Most researchers is thought, puerarin injection be take 50% propylene glycol as solvent formulated, unavoidably because the difference generation purity of the aspects such as extraction process, technology is inadequate, introduce impurity and cause various reactions (to see that the analysis > > of untoward reaction appears in the < < that Xu Xianghui writes to clinical use puerarin injection, journal of shanghai Chinese medicine, 2006,40 (8): 71-72; The clinical practice of the < < puerarin that He Xu generation state writes and untoward reaction > >, time precious traditional Chinese medical science traditional Chinese medicines, 2005,16 (12): 1307-1308).After analyzing, 63 routine puerarin untoward reaction of the domestic main medical journals of Chinese report to 2000-2004 find male 40 examples, female's 23 examples; Year at age 34～81 (57.5 ± 23.5).All cases are intravenous drip administration.Dosage is 0.4～0.6g, and medicine diluent is 5% Glucose Liquid, normal saline, 5% glucose saline etc.The fastest person of reacting generating time is 3min, and the slowest person is 13d, all occurs in administration process.There are responder 47 examples in first administration, responder 16 examples appear in repeat administration.Statistics shows, common adverse reactions has allergy (generate heat, tremble etc., 24 examples), anaphylactic shock (4 example), hemolytic anemia (13 example), hepatic injury, renal damage (7 example), drug fever (10 example), dead (5 example).All cases are all without allergies, and after reaction occurs, drug withdrawal all recovers (except death) through anti symptom treatment.Dosage and used diluent are in package insert prompting range, and institute responds all certainly as due to puerarin.The generation of untoward reaction and suffer from disease independent, have nothing to do with age, sex, contacts without much with drug dilution liquid.Relevant with patient's body constitution difference, particularly elderly and infirm easily occurs.The length of reacting generating time is relevant with the slow degree of Chinese medicine preparation onset (sees the flourish routine document analysis > > of < < puerarin untoward reaction 63 writing whole-heartedly, modern combination of Chinese and Western medicine magazine, 2005,14 (1): 140).Quiet about 10min of puerarin of one patient, appear as acute renal insufficiency, hemolytic anemia (is shown in the < < Puerarin and hemolytic anemia > > that Guan Minghua writes, adverse effect magazine, 2003,5:291).Therefore the hemolytic anemia that, puerarin causes is due to puerarin itself.
Summary of the invention
The object of the present invention is to provide the new purposes of vitamin E medicine, i.e. the application of vitamin E in puerarin injection, vitamin E can effectively be prevented and treated the intravascular hemolysis untoward reaction that puerarin brings out.
In fact, the present invention relates to the application of vitamin E when preparing puerarin injection with compound preparation, also can with puerarin injection with injection and transfusion the interim fit applications of mode, or with injection and transfusion mode application vitamin E after then apply again puerarin injection.
For achieving the above object, the technical solution used in the present invention is: vitamin E is being prepared the new purposes of puerarin injection.Vitamin E and puerarin injection are with the interim fit applications of mode of injection and transfusion.After the mode application vitamin E with injection and transfusion, then apply again puerarin injection.
Related content in technique scheme is explained as follows:
1,, in such scheme, described injection, contains following weight portion medicine: vitamin e1～50 part, 1～5000 part of puerarin.
2,, in such scheme, described injection, also contains adjuvant 1～50 weight portion, water for injection 1～10000 weight portion.Described adjuvant is sodium bicarbonate solution, Glucose Liquid, propylene glycol liquid, glucose saline, sodium chloride injection or normal saline.
3,, in such scheme, described injection can be acceptable injection, powder pin or transfusion clinically.
4,, in such scheme, the preparation method of described injection is as described below:
Described powder pin, is made by vitamin E and puerarin mixing, sterilizing; Or by vitamin E, puerarin and sodium chloride, mixed, be dissolved in water for injection, then adjust pH value to 5.0-8.5 with hydrochloric acid or sodium bicarbonate solution, filter, after filtrate sterilizing, be potted in powdery ampoule sterilizing again and make;
Described injection.By vitamin E, puerarin and sodium chloride, mixed, be dissolved in water for injection, then adjust pH value 5.0-8.5 with hydrochloric acid or sodium bicarbonate solution, filter, filtrate is potted in sterilizing in ampoule and makes.Or vitamin E is by 5% Glucose Liquid, 5% glucose saline, propylene glycol liquid (is formed by propylene glycol and normal saline (1: 1) configuration by volume, include propylene glycol 0.5ml/ml), sodium chloride injection or physiological saline solution, mix with puerarin injection, filter, filtrate is potted in sterilizing in ampoule and makes.
Described transfusion, is mixed by vitamin E, puerarin and sodium chloride, is dissolved in water for injection, then adjusts pH value 5.0-8.5 with hydrochloric acid or sodium bicarbonate solution, dissolves, and filters, and filtrate is potted in sterilizing in saline vial and makes.Or vitamin E is by 5% Glucose Liquid, 5% glucose saline, propylene glycol liquid (is formed by propylene glycol and normal saline (1: 1) configuration by volume, include propylene glycol 0.5ml/ml), sodium chloride injection or physiological saline solution, mix with puerarin injection, filter, filtrate is potted in sterilizing in ampoule and makes.
5,, in such scheme, described interim fit applications refers in hospital, mixes together transfusion or injection in application puerarin injection with vitamin E.
6, in such scheme, described then applies puerarin injection after the mode application vitamin E with injection and transfusion again, refer in hospital, after the mode application vitamin E of injecting and infusing, then follow the mode application puerarin injection with injection and transfusion.
Puerarin has and has coronary artery dilator and cerebrovascular, reduction myocardial oxygen consumption, improves the effect of microcirculation and antiplatelet aggregation.Clinically for auxiliary treatment coronary heart diseases and angina pectoris, myocardial infarction, retina arteriovenous obstruction, sudden deafness and ischemic cerebrovascular, infantile viral myocarditis, diabetes etc.Puerarin can be made compound puerarin injection for preventing and treating various diseases with vitamin E compatibility, as for preventing and treating diabetic peripheral neuropathy, hypertension complicated with diabetes mellitus, diabetic nephropathy, acute cerebral infarction, stable angina pectoris, Lower extremity deep venous thrombosis and vertigo due to vertebrobasilar insufficiency etc.But, containing the puerarin in puerarin injection, very easily cause intravascular hemolysis.Vitamin E has biological effect widely, and present inventor, through studies confirm that vitamin E also has the intravascular hemolysis untoward reaction that antagonism is brought out by puerarin, improves the safety of puerarin injection administration.
Below in conjunction with the furthermore bright objects of the present invention of some tests and the effect that can reach.
Technological guidance's principle > > of this laboratory reference < < Chinese medicine, natural drug zest and hemolytic research carries out trial test to hemolytic test, find that 8mM puerarin can cause 1% sheep red blood cell (SRBC) haemolysis 10%, external hemolytic test probability of happening is 100%, hemolytic test result is all reappeared, and illustration method can repeat.The method can be used for finding the potential accidental haemolysis of injection, is to carry out the feasible test method that injection new drug development judges whether to exist sporadic haemolysis, is conducive to reduce the generation of untoward reaction, improves the safety of injection.
Effect and the effect of the injection haemolysis untoward reaction that, vitamin E antagonism contains puerarin
(1) puerarin injection hemolytic test
Research vitamin E and puerarin share the impact on sheep red blood cell (SRBC).Get the erythrocyte of the cold sheep of 10 little tails, the vitamin E and the puerarin that add respectively doses, after 10min, observe erythrocytic state and haemolysis incidence rate, with X2 inspection statistics, analyze experimental result, seek the antagonism of vitamin E to the sporadic haemolysis of puerarin injection.Now that report the test is as follows:
1 experiment material
1.1 tested medicines
Vitamin E injection 1., produced by Baiyunshan Pharmaceutical General Factory by vitamin E, specification 100mg/ grain.With normal saline solution, dissolve and dilute.With 10mL volumetric flask, be settled to 10mL, this be injection 1., concentration is 10mgmL
-1, with microporous filter membrane (0.22 μ m) filtration sterilization, 4 ℃ of preservations.
Injection is 2.: with sterile saline, 1. injection is diluted to 1mgmL
-1, 10mL, 4 ℃ save backup.
Injection is 3.: with sterile saline, 1. injection is diluted to 0.1mgmL
-1, 10mL, 4 ℃ save backup.
Puerarin injection is 4.: by Kang Enbei Zhejiang Pharmaceutical Co, provided, and 2mL, batch number 090501, every mL injection is containing puerarin 50mg.
Puerarin injection (250mM) is 5.: with electronic balance, accurately take puerarin powder (purchased from Jiangsu Tian Sheng medicine company limited) 1.041g, with 40% dimethyl sulfoxide (DMSO, DZ0231, AMRESCO) dissolve, ultrasonic dissolution assisting, normal saline solution is diluted to 9mL, and volumetric flask is settled to 10mL, and solution colour is colourless (configuration surroundings: carry out in superclean bench).Solvent is 40%DMSO solution.With microporous filter membrane (0.22 μ m) filtration sterilization, 4 ℃ of preservations.
Compound puerarin injection is 6.: get 1. 0.04mL of injection, injection is 0.27mL 4., mixes, and 6. 0.31mL, form injection altogether.Every mL injection is containing puerarin 43.55mg, vitamin E 1.29mg.
Compound puerarin injection is 7.: get 2. 0.04mL of injection, injection is 0.27mL 4., mixes, and 7. 0.31mL, form injection altogether.Every mL injection is containing puerarin 43.55mg, vitamin E 0.129mg.
Compound puerarin injection is 8.: get 3. 0.04mL of injection, injection is 0.27mL 4., mixes, and 8. 0.31mL, form injection altogether.Every mL injection is containing puerarin 43.55mg, vitamin E 0.0129mg.
Compound puerarin injection is 9.: get 1. 0.04mL of injection, injection is 0.13mL 5., mixes, and 9. 0.17mL, form injection altogether.Every mL injection is containing puerarin 79.61mg, vitamin E 2.35mg.
Compound puerarin injection is 10.: get 2. 0.04mL of injection, injection is 0.13mL 5., mixes, and 10. 0.17mL, form injection altogether.Every mL injection is containing puerarin 79.61mg, vitamin E 0.235mg.
Compound puerarin injection
: get 3. 0.04mL of injection, injection is 0.13mL 5., mixes, and 0.17mL, forms injection altogether
.Every mL injection is containing puerarin 79.61mg, vitamin E 0.0235mg.
1.2 laboratory animal
Little tail 10 of the sheep (20～30Kg) that tremble with fear, are provided by Xibei Univ. of Agricultural & Forest Science & Technology's zoopery center.15～25 ℃ of room temperatures, under relative humidity 50% condition, raise.
1.3 reagent, instrument
Chloride injection agent, lot number: 31213042402, Shiyao Yinhu Pharmaceutical Co., Ltd. produces; Water for injection, self-control; TGL-16B high speed centrifuge, Hunan Xingke Scientific Instrument Co., Ltd.; HPY-01B biochemical cultivation case, Huangshi Hengfeng Medical Devices Co., Ltd.; BIO-RAD680 microplate reader; Enzyme mark bar is purchased by Haimen, Jiangsu San Hexingya medical apparatus and instruments factory and is produced, purchased from Shaanxi Province Yang Ling Bao Xin equipment company limited.
2 methods
The preparation of 2.1 red blood cell suspensions
10 of the cold sheep of little tail, carry out respectively hemolytic experiment.Every sheep is adopted jugular vein blood 10mL, after heparin sodium (Jiangsu Wanbang Biological Pharmaceutical Co., Ltd.) 160IU anticoagulant, is placed in graduated centrifuge tube, centrifugal 10 minutes with 2000 revs/min, discard blood plasma, add appropriate chloride injection agent washing, centrifugal abandoning supernatant and leukocytic cream.Add again appropriate normal saline shake up, centrifugal, so cyclic washing is 3 times, till being water white transparency to centrifugal rear supernatant.Gained packed red cells is become to the red cell suspension of 11% (volume ratio) with normal saline dilution.So far, red cell suspension is ready.
The outer hemolytic experiment design of 2.2 puerarin solution bodies
If puerarin solution effects is 8mM (0.00333gmL in erythrocytic concentration
-1).If negative control group, solvent control group (replacing puerarin solution effects in erythrocyte with DMSO), drug treating group and positive controls.The pH value of measuring puerarin solution with the desk-top pH meter of METTLER TOLEDO is 7.16.
Shown in following table 1, in test tube, add corresponding composition respectively, note application of sample order.Often add after a kind of composition, all shake up gently.After all adding in system etc. all the components in system, light shaking mixes, and places the biochemical cultivation case incubation of 37 ℃.After 10min, observe haemolysis and aggregation.Aggregation decision method: if having rufous or brownish red flocculent deposit in solution, not disperseing after jolting, show to have red cell agglutination to occur, if can be uniformly dispersed again after condensation product jolting, is pseudoagglutination, is true coagulation if condensation product does not shake loose person.Then each pipe is centrifugal according to 5000rpm/min condition, perusal supernatant fluid color.Get supernatant, in 540nm wavelength place, detect absorbance value (OD value).Technological guidance's principle > > according to < < Chinese medicine, natural drug zest and hemolytic research in 2005, calculates the hemolysis rate (%) of respectively organizing each pipe by formula:
Hemolysis rate (%)=(drug treating group OD value-negative control group OD value)/(positive controls OD value-negative control group OD value)
With reference to evaluation criterion: hemolysis rate > 5%, show to have haemolysis to occur, and carry out statistical procedures.
The external hemolytic experiment packet design of table 1 puerarin solution and vitamin E
3 results
This test is investigated when puerarin 8mM concentration, and puerarin injection sporadic hemolytic experiment research 4., is 5. carried out in 100 μ g/mL, 10 μ g/mL, 1 impact of μ g/mL vitamin E on 10 sheep red blood cells simultaneously, and experimental result all has itemized record, uses X
2inspection statistics is analyzed, and the results are shown in Table 2.
10 sheep hemolytic test result statistical tables of table 2
Note: compare a P < 0.01 with the negative group of normal saline; With the comparison of puerarin injection group, b P < 0.01
Result shows: haemolysis does not appear in normal saline group, the whole haemolysis of water for injection group: with the comparison of normal saline group, puerarin injection 4., 5. group all occurs that haemolysis, haemolysis incidence rate and normal saline group exist utmost point significant difference (P < 0.01); Hemolytic test result is all reappeared, and illustrates that this hemolytic experiment method is reliable and stable, and result of the test can repeat.With puerarin injection 4., 5. group relatively, compound puerarin injection 6., 7., 8., 9., 10.,
all there is not haemolysis in each group, compound puerarin injection 6., 7., 8., 9., 10.,
each organize haemolysis incidence rate all with puerarin injection 4., there is utmost point significant difference (P < 0.01) in group 5.; With the comparison of normal saline group, compound puerarin injection 6., 7., 8., 9., 10.,
each organize haemolysis incidence rate all with normal saline group zero difference (P > 0.05); Compound puerarin injection 6., 7., 8., 9., 10.,
4., 5. to organize puerarin concentration identical with puerarin injection for each group, is 8mM, but compound puerarin injection 6. and 9., 7. and 10., 8. and
contain respectively 100 μ g/mL, 10 μ g/mL, 1 μ g/mL vitamin E, and 4., 5. puerarin injection is respectively organized and is not contained vitamin E.Above results suggest: the application of the vitamin E of variable concentrations and puerarin compatibility, the haemolysis untoward reaction of all can antagonism being brought out by puerarin, and can make incidence rate be reduced to normal saline level.
Above experimental result shows: puerarin can cause haemolysis, and the injection that contains puerarin all likely causes haemolysis, after adding vitamin E, all can eliminate the haemolysis untoward reaction containing puerarin injection.
Above-mentioned result of the test prompting: the injection that puerarin injection and puerarin and vitamin E compatibility are made has no the generation of hemolytic reaction.
Therefore, when preparation contains the injection of puerarin or while applying puerarin injection, add vitamin E, can eliminate the haemolysis untoward reaction that puerarin causes, improved the safety of puerarin injection administration.
Advantage of the present invention is: when preparation contains the injection of puerarin or while applying puerarin injection, adds vitamin E, there is the intravascular hemolysis untoward reaction that good antagonism is brought out by puerarin, and inexpensive, have no side effect, safety.
Below in conjunction with embodiment, the invention will be further described:
The specific embodiment:
The preparation of embodiment 1:(compound puerarin injection)
Get vitamin e1 g, puerarin 10g, adds sodium chloride 9g, adds water to 1000mL, with 1M hydrochloric acid or sodium bicarbonate solution, adjusts pH to 5.0-8.5, filter, filtrate be potted in 2,5 or the ampoule of 10mL in, 100 ℃ of sterilizing 30min, obtain injection.This product can be used for auxiliary treatment coronary heart diseases and angina pectoris, myocardial infarction, artery Venous blocks of retina, sudden deafness and ischemic cerebrovascular, infantile viral myocarditis, diabetes etc.This product can intravenous injection or intramuscular injection, each 1～500mL, and 1～3 time on the one 10～20 days is a course for the treatment of, can use continuously 2～3 courses for the treatment of.
The preparation of embodiment 2:(compound puerarin powder pin)
Get vitamin e1 00mg, puerarin 1g, is potted in the powder pin ampoule of 10mL, and 100 ℃ of sterilizing 30min, obtain powder pin.This product can be used for auxiliary treatment coronary heart diseases and angina pectoris, myocardial infarction, artery Venous blocks of retina, sudden deafness and ischemic cerebrovascular, infantile viral myocarditis, diabetes etc.During application, will make powder pin 1～5000mg and sodium chloride injection or normal saline solution and mix, can carry out intravenous injection or intramuscular injection, each 1～500mL, 1～3 time on the one 10～20 days is a course for the treatment of, can use continuously 2～3 courses for the treatment of.
The preparation of embodiment 3:(compound puerarin transfusion)
Get vitamin e1 0mg, puerarin 2g, sodium chloride 9g, adds water to 1000mL, with 1M hydrochloric acid or sodium bicarbonate solution, adjusts pH to 5.0-8.5, filters, and filtrate is potted in the saline vial of 250mL, and 100 ℃ of sterilizing 30min, are infused.This product can be used for auxiliary treatment coronary heart diseases and angina pectoris, myocardial infarction, artery Venous blocks of retina, sudden deafness and ischemic cerebrovascular, infantile viral myocarditis, diabetes etc.During application, can directly carry out intravenous injection or intramuscular injection, each 1～500mL, 1～3 time on the one 10～20 days is a course for the treatment of, can use continuously 2～3 courses for the treatment of.
Above-described embodiment is only explanation technical conceive of the present invention and feature, and its object is to allow person skilled in the art can understand content of the present invention and implement according to this, can not limit the scope of the invention with this.All equivalences that spirit is done according to the present invention change or modify, within all should being encompassed in protection scope of the present invention.
Claims (8)
1. the application of vitamin E in puerarin injection.
2. application according to claim 1, it is characterized in that: vitamin E can be made compound injection application with puerarin injection, also can with interim the cooperation simultaneously of mode of injection and transfusion, apply with puerarin injection, or then apply again puerarin injection after the mode application vitamin E with injection and transfusion.
3. application simultaneously according to claim 2, is characterized in that: puerarin injection and vitamin E injection mix before for patient's application, then applies in the mode of injection and transfusion.
4. after the mode application vitamin E with injection and transfusion according to claim 2, then apply again puerarin injection, it is characterized in that: first for after patient applies vitamin E injection and finish, more then apply puerarin injection.
5. according to the injection described in claim 1,2,3,4 and the application of injection, it is characterized in that: contain following weight portion medicine: vitamin e1～50 part, 1～5000 part of puerarin.
6. according to the injection described in claim 1,2,3,4,5 and the application of injection, it is characterized in that: can contain adjuvant 1～50 weight portion, water for injection 1～10000 weight portion.
7. according to the injection described in claim 1,2,3,4,5,6 and the application of injection, it is characterized in that: described adjuvant can be sodium bicarbonate solution, Glucose Liquid, glucose saline, propylene glycol liquid, sodium chloride injection or normal saline solution.
8. according to the injection described in claim 1,2,3,4,5,6 or 7 and the application of injection, it is characterized in that: described injection and the application of injection can be acceptable injection, powder pin or transfusion clinically.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101991533A (en) * | 2010-10-26 | 2011-03-30 | 西安力邦制药有限公司 | Puerarin liposome microsphere injection and preparation method thereof |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101991533A (en) * | 2010-10-26 | 2011-03-30 | 西安力邦制药有限公司 | Puerarin liposome microsphere injection and preparation method thereof |
Non-Patent Citations (4)
| Title |
|---|
| FANG WANG ET AL.: "Vitamin E inhibits hemolysis induced by hemin as a membrane stabilizer", 《BIOCHEMICAL PHARMACOLOGY》 * |
| NICHOLAS R. BROWNLEE ET AL.: "Role of vitamin E in glutathione-induced oxidant stress: methemoglobin, lipid peroxidation and hemolysis", 《JOURNAL OF LIPID RESEARCH》, vol. 18, 31 December 1977 (1977-12-31), pages 635 - 644 * |
| 侯少贞: "葛根素注射液致溶血反应的机制研究", 《《中国博士学位论文全文数据库 医药卫生科技辑》》 * |
| 王洪宝: "葛根素注射液溶血毒性机制研究", 《中国优秀硕士学位论文全文数据库》, no. 4, 15 April 2011 (2011-04-15) * |
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Application publication date: 20140903 |