CN103040946A - Application of lotus nut total alkaloids in preparation of medicament for treating vital myocarditis - Google Patents
Application of lotus nut total alkaloids in preparation of medicament for treating vital myocarditis Download PDFInfo
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- CN103040946A CN103040946A CN2013100355184A CN201310035518A CN103040946A CN 103040946 A CN103040946 A CN 103040946A CN 2013100355184 A CN2013100355184 A CN 2013100355184A CN 201310035518 A CN201310035518 A CN 201310035518A CN 103040946 A CN103040946 A CN 103040946A
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- total alkaloids
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- plumula nelumbinis
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Landscapes
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention provides application of lotus nut total alkaloids in preparation of a medicament for treating vital myocarditis. The medicament for treating the vital myocarditis provided by the invention has good efficacy on an acute stage and a chronic stage, and a traditional Chinese medicine is consolidated and lasting in efficacy, low in toxic and side effects and cheap in price.
Description
Technical field
The present invention relates to the new purposes of Plumula Nelumbinis total alkaloids.Belong to drug world.
Background technology
Viral myocarditis refer to by Coxsackie virus, dust can (ECHO), poliomyelitis, the influenza infection myocardium limitation or the diffuse acute or chronic inflammatory disease pathological changes that cause, belong to infectious cardiomyopathy.Account for 40% by the Coxsackie virus infection causer.Other virus has: dust can (ECHO), poliomyelitis, influenza, parainfluenza virus, measles, parotitis, encephalitis B, hepatitis virus, varicella zoster virus, cytomegalovirus, HIV (human immunodeficiency virus), infectious monocytosis etc.Virus function is directly to invade little blood vessel injury in cardiac muscle and the cardiac muscle in the mode of cardiac muscle.Producing cardiac damage by immunologic mechanism plays an important role in myocarditic morbidity.The direct infringement of virus and immunoreation mediation cause the myocardial cell infringement, make heart systolic and diastolic function obstacle; If pathological changes is involved pace-making or the conducting systems such as sinuatrial node, atrioventricular node, bundle branch, then can cause various types of arrhythmia.Clinical main manifestations often has first the symptoms such as heating, systemic pain, pharyngalgia, asthenia, nausea,vomiting,diarrhea for patient, cardiopalmus, uncomfortable in chest, chest pain or pareordia dull pain, dizziness, dyspnea, edema then occur, even the Adams-Stokes syndrome; Heart failure or cardiogenic shock appear in only a few patient.
The Plumula Nelumbinis source is dry spire and radicle in the mature seed of nymphaeaceae plant lotus (Nelumbo nucifera Gaertn.).Fujian, main product ground, Hunan etc.The Plumula Nelumbinis chemical constituent mainly contains: outside liensinine, isoliensinine, the (-)-Neferine, also contain nuciferine, pronuciferine (+)-Pronuciferine and water-soluble alkaloid C19H23NO3, S-N-methyl coclaurine (S-N-methyIisococlaurine) and dl-armepavine (dl-armepavine).Except containing alkaloid, also contain flavones ingredient in the Plumula Nelumbinis: the chemical compounds such as rutin, hyperin, luteolin; Separate from the puny polar components of Plumula Nelumbinis again in recent years and obtain 7 chemical compounds such as Palmic acid, cupreol, cupreol-3-o-β-D-Glucose glycoside, cupreol normal octane acid esters and cupreol Palmic acid.Wherein cupreol normal octane acid esters and cupreol Palmic acid system gets in this plant first.From the Plumula Nelumbinis plumule, separate and obtain multiple volatile oil component: hyaluronic acid, pentadecanoic acid, palmitic acid, heptadecanoic acid, linoleic acid, stearic acid, arachidic acid, heneicosanoic acid, behenic acid, lignoceric acid, Squalene etc.Also contain in addition the trace element such as chlorophyll, water soluble polysaccharide and zinc, copper, ferrum, calcium, magnesium sodium, potassium, nickel, manganese, cadmium in the Plumula Nelumbinis.The Plumula Nelumbinis total alkaloids document of report is more at present, as: Liu Wei, Deng, the preparation technology of Plumula nelumbinis Alkaloid drop pill and assay, CHINA JOURNAL OF CHINESE MATERIA MEDICA, the 7th phase of the 32nd volume April in 2007, reported that the Plumula nelumbinis Alkaloid main component is 3 kinds of bisbenzylisoquinoline alkaloids such as (-)-Neferine, isoliensinine and liensinine, can be used for treating the arrhythmia symptom that is caused by the multiple heart disease such as myocardial ischemia, coronary heart disease.Li Juan, etc., processes of alkaloids from Lotus plumule health care progress, grain and oils and fats, have reported that processes of alkaloids from Lotus plumule has the multiple medicinal and health cares such as blood pressure lowering, antioxidation, protection cardiac muscle at the 1st phase in 2010.
Summary of the invention
Technical scheme of the present invention has provided the total biological new purposes of Plumula Nelumbinis.
The invention provides the purposes of Plumula Nelumbinis total alkaloids in the medicine of preparation treatment viral myocarditis.
The present invention also provides the purposes of Plumula Nelumbinis total alkaloids in the medicine of the anti-Coxsackie virus of preparation.Wherein, described Coxsackie virus is Coxsackie B virus.Further preferably, described Coxsackie virus is Coxsackie B virus 3m.
Wherein, described Plumula Nelumbinis total alkaloids derives from dry spire and radicle in the mature seed of nymphaeaceae plant lotus (Nelumbo nucifera Gaertn.).
Wherein, in the described Plumula Nelumbinis total alkaloids weight percentage of total alkaloids more than 70%.
Wherein, described medicine is take the Plumula Nelumbinis total alkaloids as active component, adds the preparation that pharmaceutically acceptable adjuvant or complementary composition are prepared from.
Wherein, described preparation is tablet, capsule, granule, drop pill.
Wherein, the weight percentage of (-)-Neferine is not less than 40% in the described drop pill, and the weight percentage of isoliensinine is not less than 12%, and the weight percentage of liensinine is for being lower than 12%.
Medicine of the present invention is used for the treatment of viral myocarditis, no matter be acute stage or chronic phase preferably curative effect to be arranged all, and the effective in cure consolidation of Chinese medicine, lasting, less, the low price of toxic and side effects.
The specific embodiment
The extraction process of embodiment 1 Plumula Nelumbinis total alkaloids of the present invention
Plumula Nelumbinis 2kg with 80% ethanol (8 times of amounts) merceration 12h, stirs extraction 3 times with electric blender after pulverizing, each 2h.Merge ethanol, decompression and solvent recovery is to proper volume, sucking filtration.Filtrate is transferred pH to 2-3 with 1% hydrochloric acid, filters, and filtrate is transferred pH to 9-10 with ammonia again, chloroform extraction for several times, combined chloroform liquid boils off solvent, drying under reduced pressure 24h gets yellow solid total alkali 20g to constant weight.Get the Plumula Nelumbinis total alkaloids.
The extraction of embodiment 2 Plumula Nelumbinis total alkaloidss of the present invention
The Plumula Nelumbinis medical material is pulverized, and adding 0.2%HCL/30% ethanol is solvent, and 6 times of quantity of solvent are extracted 3 times, each 1h.Select D101-A purification with macroreticular resin Plumula nelumbinis Alkaloid, with behind distilled water, 4 times of resin volumes removals of the 15% ethanol elution water-solubility impurity, with 4 times of resin volumes of 70% ethanol elution enrichment total alkaloids, the pressure reducing and steaming solvent is dried to constant weight first.The total alkali extracting solution of Plumula Nelumbinis is after purification by macroporous resin is processed, and refined yield is the highest, and total alkaloid content gets the Plumula Nelumbinis total alkaloids more than 70%.
The preparation of embodiment 3 Plumula Nelumbinis total alkaloids drop pill of the present invention
Plumula Nelumbinis total alkaloids extract (embodiment 1 or embodiment 2 preparations) is 1:5 with containing 70%PEG4000 substrate ratio, and 85 ℃ of fluid temperature, liquid coolant are dimethicone, 10 ℃ of chilling temperatures, and the cooling column length is 80cm, drips apart from 3.5cm, drips 25/min of speed.Use high effective liquid chromatography for measuring, the (-)-Neferine average content must not be and is lower than 40%, and the isoliensinine average content must not be and is lower than 12%, and the liensinine average content must not be lower than 12%.
This preparation can be tablet, capsule, and soft capsule (soft gelatin capsule), the pharmacy such as pill can be for the form of administration.
Except the Plumula Nelumbinis total alkaloids of embodiment 1 and embodiment 2 preparations, also comprise the Plumula Nelumbinis total alkaloids of the method preparation of adopting present bibliographical information.
Below prove beneficial effect of the present invention by concrete clinical trial and pharmacodynamics test.
Test example 1 medicine therapeutic virus myocarditis clinical observation on the therapeutic effect of the present invention
1 data and method
1.1 clinical data is chosen in the attached the People's Hospital of Fujian university of TCM viral myocarditis (VMC) patient 60 examples of being in hospital, male 27 examples, women 33 examples, year at age 8～39 (21.3 ± 3.5), 1 month～2.5a of the course of disease, average 0.55a.All meet the VMC diagnostic criteria of national myocarditis cardiomyopathy symposium in 1999 revision, sick have the acute viral infection history in front 1～3 week, and main clinical manifestation is heating, cardiopalmus, pain uncomfortable in chest, breathe hard, weak and arrhythmia; Electrocardio diagram sinus tachycardia, non-specific multipole and intraventricular block; Ultrasonic cardiography diagram cardiac dilatation and myocardium shrinkage function are incomplete; Myocardial enzymes increases, and cardiac muscle biopsy has the characteristic inflammation to change.Be VMC with reference to " new Chinese medicine treatment viral myocarditis guideline of clinical investigations " standard diagnostics, and the heresy that meets differential diagnosis in tcm feel frustrated the moon, deficiency of both QI and YIN, deficiency of both YIN and YANG syndrome.Get rid of hyperthyroidism, beta receptor hyperfunctioning and other heart diseases, gestation and women breast-feeding their children have drug allergy history or allergic constitution person.The patient is divided into treatment group, each 30 example of matched group at random, and two groups of clinical datas have comparability.
1.2 quiet polarized solution of Therapeutic Method matched group (10% Glucose Liquid 500ml+ insulin 8U+10% potassium chloride 10m1), 1 time/d; Oral ubiquinone
1010mg, vitamin C 0.2g, 3 times/d; Take the circumstances into consideration to use general anti-arrhythmic, be 4 weeks the course for the treatment of.Treatment group oral drugs group (embodiment 3) 4 tablets/times, 4 times/d; Take the circumstances into consideration to use general anti-arrhythmic, be 4 weeks the course for the treatment of.During the treatment, observe two groups of clinical manifestations, 24h ambulatory electrocardiogram, Myocardial Enzymologic and changes of cardiac function.Criterion of therapeutical effect with reference to " new Chinese medicine treatment viral myocarditis guideline of clinical investigations " is judged curative effect.
1.3 detection method is the 24h dynamic ecg recordings examination 1.: adopt Holter to detect two groups of 24h ambulatory electrocardiograms.2. Myocardial Enzymologic detects: adopt automatic clinical chemistry analyzer to detect two groups of lactic acid dehydrogenases (LDH) and creatine kinase isozyme (CK.MB).3. antiviral antibody detects: adopt ELISA method, IgM enzyme-linked immunologic detecting kit to detect two groups of Coxsackie B virus antibody.4. cardiac function detects: adopt color doppler ultrasonography two groups of left cardiac ejection fractions of detection aroused in interest (LVEF) and cardiac index (CI).
1.4 statistical method adopts the SPSS11.0 statistical software, data are used
Expression, measurement data are relatively with the t check, and enumeration data is relatively with check.There is statistical significance P≤0.05 for difference.
2 results
28 examples 2.1 the clinical efficacy treatment group is clearly better or takes a turn for the better, invalid 2 examples, effective percentage 93.3%; Matched group is respectively 20,10 examples, effective percentage 66.7%.The treatment group effective percentage obviously is better than matched group (P＜0.05).
2.224h the premature beat of ambulatory electrocardiogram performance treatment group takes a turn for the better or recovers 14 examples, ST-T changes recovery 11 examples, and atrioventricular block improves 8 examples; Matched group is respectively 7,4,5 examples.Two groups more all have significant difference (P＜0.05 or＜0.01).
The situation 2.3 lab testing is turned out cloudy, coxsackie B antibody positive 23 examples before the treatment group treatment, 19 examples of turning out cloudy after the treatment; Matched group is respectively 21, the l0 example.Two groups relatively have significant difference (P＜0.05).The myocardium enzyme variation sees Table 1 before and after two groups of treatments.
Myocardium enzyme variation before and after the table 1 liang group treatment (U/L,
)
Annotate: with comparison after the treatment of control group, * P＜0.05, * * P＜0.01.
2.4 LVEF, CI are respectively (43.97 ± 6.95) %, 2.5 ± 0.8, (57.98 ± 6.81) %, 3.5 ± 0.7 before and after the treatment of changes of cardiac function treatment group; Matched group is respectively (44.15 ± 5.84) %, 2.6 ± 0.8, (53.11 ± 8.15) %, 3.2 ± 0.5.More equal no difference of science of statistics before two groups of treatments (P is equal〉0.05), significant difference (P＜0.05) is more all arranged after the treatment.
Test example 2 medicines of the present invention infect Balb/c mouse core myositis therapeutical effect to Coxsackie B virus 3m
Material
1. the male Balb/c mice of animal cleaning level is 240,4-6 age in week, weight (14 ± 2) g.
2. viral CVB3m(Nancy strain), introduced by U.S. ATCC.
3. instrument computer image analysis instrument (three-hypers CMISA series is developed jointly by Beijing Aviation university picture centre and Beijing Zhong Shan Bioisystech Co., Ltd); CO2 incubator (U.S. Nuaire-4950E); Microplate reader (Bio-RAD, Bench mark); Inverted microscope (German LECIA); Ultra cold storage freezer (MDF382E, Japanese SONY).
4. reagent D MEM(Dulbecco ' s Modified Eagle Media) available from U.S. Gibco company; Hyclone (TBD0032HYP) is available from U.S. Gibco company.
Method
1. medicine prepares above-mentioned Plumula Nelumbinis total alkaloids (embodiment 2).
2. grouping is divided into 6 groups with modeling at random with 288 Balb/c mices, and namely the high, normal, basic Three doses group of medicine group, the positive are organized the model group of viral myocarditis and Normal group.Every group is 48.The CVB3m virus liquid of the equal lumbar injection 0.1mL of model group and medication therapy groups 50tissue infection dose (tissue culture infective dose, TCID50), normal group give the culture fluid lumbar injection that equivalent does not contain virus.
The administration modeling simultaneously treatment group by (in primary crude drug 10g Plumula Nelumbinis medical material/kg) give the medicine gavage, positive group dosage is the 50mg/kg(virazole); Model group and normal group give respectively equivalent distilled water gavage, continuously gavage 14d.
4. experimental index
4.1 observe fur, stool, the mental status that mice is respectively organized in general state observation every day, the periodic measurement weight.
4.2 calculate survival rate mice 14d survival rate=respectively organize survival mice number/respectively organize total mice * 100%.
Every group of the modeling the 3rd, 5,7,10 4.3 draw materials, 14d are got 6 at random, weigh; It is dirty to core, and sucks residual blood and the tissue fluid of heart tissue with filter paper, carries out precise weighing, calculates heart/weight (%)=cardiac mass (g)/weight (g) * 100%.Vertically cut along the left ventricle axle, the heart right-hand part is put into the EP pipe, places rapidly curling stone to save backup; Remainder is fixed for histopathology with 4% paraformaldehyde and detects.
4.4 the CVB3m of cardiac muscular tissue virus titer is measured the dirty right half part of coring and shredded with eye scissors, grinds, 4 ℃ of centrifugal 10min of 2000r/min get supernatant, with protein-nucleic acid analysis-e/or determining protein concentration, get 0.2mL from 10
-1To 10
-8Doubling dilution is inoculated on the Microtitration plates that grows up to monolayer Hela cell, cultivates 48h for 37 ℃, and the observation of cell pathological changes adopts the Reed-Muench method to measure the TCID50 of virus in the cardiac muscular tissue, the virus titer of calculating myocardium homogenate.
4.5 myocardium pathology histology is made pathological section with cardiac muscular tissue, puts microscopically and observes.Adopt image analysis system, the thought-read flesh gross area and the pathological changes gross area and focus sum calculates the pathology integration=pathological changes gross area/institute thought-read flesh gross area * 100 respectively.
5 serum cardiac enzymatic determinations
Each is organized mice and plucks eyeball and get blood, shake up gently, in 4 ℃, the centrifugal 10min of 3000r/min, separated plasma, content with aspartate transaminase (AST), lactic acid dehydrogenase (LDH), creatine kinase (CK), creatine kinase isozyme (CK-MB) etc. in the microplate reader mensuration serum operates according to the test kit description.
6. statistical method adopts SPSS11.5 medical statistics software to analyze, measurement data with
Expression, 3 groups measurement data adopts monofactorial variance analysis, relatively adopts in twos the LSD analytical method.
χ is adopted in the rate analysis of enumeration data
2Check.
The result
1. the model group 3d mice activity that affects of mice general state reduced, appetite reduces, and fur is filthy, and suffering from diarrhoea appears in the part mice.5-7d mice lethargy moves curling oneself up less, and weight obviously alleviates, and dead mouse is counted showed increased.10-14d survival mice state takes a turn for the better gradually, and goodbye does not have dead mouse.Each administration group mice fur, activity, diet situation obviously are better than model group.
2. the impact of Mice Body quality seen Table 2.Before the modeling, each organizes Mice Body quality there was no significant difference.Weight presents downward trend after the model group mouse infection virus; Descending in various degree also appears after infection in each treatment group weight, but fall is lower than model group (P＜0.05), but low dose group is compared without significance with model group.The weight difference of each time point is not remarkable between 3 groups.
Table 2 respectively organize Mice Body mass change situation (
N=6, g)
Annotate: compare * P＜0.05, * * P＜0.01 with model group.
3. the impact of mouse survival rate seen Table 3.The mouse survival number of 3 various dose administration groups is obviously more than model group.The survival rate of 14d model group is 68.75%, and high dose group is 87.5%, and middle dosage group is 89.58%, and low dose group is that the percentage survival of 79.17%, 3 treatment group all is higher than model group, has significant difference (P＜0.05=; Survival rate difference between 3 groups is not remarkable.
Table 3 is respectively organized survival rate (n=48, %) in the mice 14d
Annotate: compare * P＜0.05, * * P＜0.01 with model group.
4. the impact of mouse cardiac muscle inner virus titre seen Table 4.3 dosage group medicines obviously all are lower than virus group (P＜0.05, P＜0.01) in various degree at metainfective virus titer.
Each 3 groups of mouse cardiac muscle inner virus titres comparison (LogTCID50) of table 4 (
N=6)
Annotate: compare * P＜0.05, * * P＜0.01 with model group;
5. the impact of mouse heart quality seen Table 5.The cardiac mass of model group/weight ratio and normal group significantly increase (P＜0.01).The ratio of the cardiac mass/weight of 3 treatment groups is compared with model group, extremely significantly reduces (P＜0.01), and the ratio difference of the cardiac mass/weight between 3 treatment groups is significantly (P＞0.05) not
Table 5 respectively organize the mouse heart quality (
N=30)
Annotate: compare * P＜0.05, * * P＜0.01 with model group.
6. the impact of mouse cardiac muscle pathological change seen Table 6.Normal group myocardial cell marshalling is without inflammatory cell infiltration.The visible myocardial cell swelling of virus model group, inflammatory cell infiltration, serious visible extent of disease increases, or is the distribution of many kitchen ranges property, myocardium cell necrosis occurs, very then can involve visceral pericardium.The myocardium pathology integration of 3 treatment groups significantly is lower than model group (P＜0.05, P＜0.01).Middle dosage group and high dose group pathological changes ratio significantly are lower than low dose group (P＜0.05).
Table 6 respectively organize mouse cardiac muscle pathology integral contrast (
N=30)
Annotate: compare * P＜0.05, * * P＜0.01 with model group;
7. after serum cardiac enzymatic determination result infected virus, AST, CK, LDH, CK-MB content all raise in the mice serum.Compare with the M group, the These parameters of each administration group is active obviously to descend.The order of curative effect from excellent to inferior that shows various medicines from twice testing result is: SM〉SH〉the SL group, wherein SM, SH group reduces LDH, CK, the CK-MB level is evident in efficacy, seeing Table 7 with the more variant P＜0.05(of M group) table 7 Plumula Nelumbinis extract is on the impact (n=10 of myocarditis serum cardiac enzyme, U/L
)
Annotate: compare * P＜0.05, * * P＜0.01 with normal group.
In sum, prove by clinical trial that medicine of the present invention is used for the treatment of viral myocarditis (VMC), drug effect is obvious, and effective percentage reaches 93.3%; Prove that by animal experiment medicine of the present invention can improve the mouse survival rate, cardiac mass, it is remarkable that Coxsackie B virus 3m is infected Balb/c mouse core myositis therapeutic effect, provides a kind of new medication to select for clinical.
Claims (9)
1. the purposes of Plumula Nelumbinis total alkaloids in the medicine of preparation treatment viral myocarditis.
The Plumula Nelumbinis total alkaloids the preparation anti-Coxsackie virus medicine in purposes.
3. purposes according to claim 2, it is characterized in that: described Coxsackie virus is Coxsackie B virus.
4. purposes according to claim 3, it is characterized in that: described Coxsackie virus is Coxsackie B virus 3m.
5. the described purposes of any one according to claim 1-3 is characterized in that: described Plumula Nelumbinis total alkaloids derives from dry spire and radicle in the mature seed of nymphaeaceae plant lotus Nelumbo nucifera Gaertn..
6. purposes according to claim 5, it is characterized in that: the weight percentage of total alkaloids is more than 70% in the described Plumula Nelumbinis total alkaloids.
7. the described purposes of any one according to claim 1-6, it is characterized in that: described medicine is take the Plumula Nelumbinis total alkaloids as active component, adds the preparation that pharmaceutically acceptable adjuvant or complementary composition are prepared from.
8. purposes according to claim 7, it is characterized in that: described preparation is tablet, capsule, granule, drop pill.
9. purposes according to claim 8, it is characterized in that: the weight percentage of (-)-Neferine is not less than 40% in the described drop pill, and the weight percentage of isoliensinine is not less than 12%, and the weight percentage of liensinine is for being lower than 12%.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104306455A (en) * | 2014-11-07 | 2015-01-28 | 中南民族大学 | Lotus plumule chloroform extract and preparation method and use thereof |
| CN111329859A (en) * | 2020-03-02 | 2020-06-26 | 复旦大学 | Application of sodium copper chlorophyllin in preparation of anti-enterovirus drugs |
| CN112691105A (en) * | 2020-07-02 | 2021-04-23 | 中国人民解放军军事科学院军事医学研究院 | New use of neferine in inhibiting SARS-CoV and SARS-CoV-2 infection |
| CN117599055A (en) * | 2023-11-17 | 2024-02-27 | 北京中医药大学 | Application of isoliensinine in preparation of antiviral drugs |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1444981A (en) * | 2003-04-30 | 2003-10-01 | 吴梅春 | Medicine for treating cardiovascular diseases and its preparing method |
| CN1593598A (en) * | 2004-07-14 | 2005-03-16 | 江苏中康药物科技有限公司 | Effective site extract of lotus plumule and its usage |
-
2013
- 2013-01-30 CN CN2013100355184A patent/CN103040946B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1444981A (en) * | 2003-04-30 | 2003-10-01 | 吴梅春 | Medicine for treating cardiovascular diseases and its preparing method |
| CN1593598A (en) * | 2004-07-14 | 2005-03-16 | 江苏中康药物科技有限公司 | Effective site extract of lotus plumule and its usage |
Non-Patent Citations (5)
| Title |
|---|
| 张京梅，等: "莲子心总生物碱的提取分离及药效学初步研究", 《中国实验方剂学杂志》 * |
| 曾淘，等: "病毒性心肌炎并发心律失常的药物治疗策略", 《临床心血管病杂志》 * |
| 王瑞芳，等: "莲子心提取物抗心律失常作用及其急性毒性研究", 《中草药》 * |
| 申元英，等: "空心莲子草抗柯萨奇病毒B_3的实验研究", 《湖北中医杂志》 * |
| 马志杰，等: "中西医结合治疗病毒性心肌炎临床研究", 《河南中医学院学报》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104306455A (en) * | 2014-11-07 | 2015-01-28 | 中南民族大学 | Lotus plumule chloroform extract and preparation method and use thereof |
| CN104306455B (en) * | 2014-11-07 | 2016-06-22 | 中南民族大学 | A kind of Plumula Nelumbinis chloroform extract and its production and use |
| CN111329859A (en) * | 2020-03-02 | 2020-06-26 | 复旦大学 | Application of sodium copper chlorophyllin in preparation of anti-enterovirus drugs |
| CN112691105A (en) * | 2020-07-02 | 2021-04-23 | 中国人民解放军军事科学院军事医学研究院 | New use of neferine in inhibiting SARS-CoV and SARS-CoV-2 infection |
| CN117599055A (en) * | 2023-11-17 | 2024-02-27 | 北京中医药大学 | Application of isoliensinine in preparation of antiviral drugs |
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