CN100438867C - Application of flavone monomer in antivirus drug preparing process - Google Patents
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Abstract
The present invention discloses an application of a flavone monomer to prepare antiviral medicine; the flavone monomer has the following chemical structural formula and belongs to the field of medicine. The present invention has the advantages that the present invention provides an antiviral monomre comound; a series of antiviral monomer experiments demonstrate that the monomer has the function of inhibiting the death caused by the monomer, and viral protein in a translation process of viruses and prompts that the monomer is used as broad-spectrum antiviral medicine. The monomer has an obvious antiviral function for picornaviruses using coxsackie viruses as a representation; thereby, the monomer provides a new selective scheme for curing viral myocarditis.
Description
Technical field
The present invention relates to the application of a kind of flavone monomer in the preparation antiviral drugs, the application of a kind of flavone monomer in the medicine of anti-picornavirus of preparation such as Coxsackie virus of more specifically saying so belongs to field of medicaments.
Background technology
Global popular in view of viral disease such as SARS, bird flu, bovine spongiform encephalopathy etc. in recent years, the exploitation antiviral drugs becomes the focus of people's extensive concern.At present, the main policies of antiviral drugs research comprises in the world: the combining, suppress reverse transcriptase, suppress the virus protein translation of blocking virus and target cell, Profilin matter is modified or sprouting of virion disengaged and cut off viral genome etc.Structure of modification, Computer Design guide's molecule, antisense oligonucleotide structure transformation and combinatorial chemistry are synthetic by known curative effect chemical compound is carried out, the development of immune function controlling agents and from plant and microorganism screening natural anti-virus lead compound etc., research and develop new antiviral drugs.
In numerous viral diseases, viral myocarditis is the commonly encountered diseases and the frequently-occurring disease of cardiovascular system, the serious threat human beings'health.At present, no matter in developed country still in developing country, myocarditic sickness rate increases than all having significantly before 10 years, its main cause is due to the sickness rate of viral myocarditis increases in the infectious myocarditis.Show according to The World Health Organization (WHO) whole world virus monitor research report: in neonate, child's sudden death case, 20% is due to the viral myocarditis; The sickness rate of viral myocarditis in neonate, child is 3,60/,100,000, and mortality rate is 8%; The sickness rate of viral myocarditis be the same period cardiovascular disease inpatient 8.69～20.8%; Viral infection is invaded after the cardiac muscle, can cause focal or diffusivity myocardium between matter ooze out and myofibrosis cordis, necrosis.Serious arrhythmia, heart failure, cardiogenic shock even sudden death can appear in serious symptom diffusivity myocarditis; Also but protracted course of disease causes cardiac hypertrophy, and develops into dilated cardiomyopathy gradually.
Drug research at viral myocarditis mainly concentrates on following several aspect both at home and abroad: the exploration of the exploitation of Coxsackie virus attenuated live vaccine, the development of immunomodulator and antiviral drugs, and also in the ascendant at the gene therapy of viral myocarditis; But aspect the research and development of anti-Coxsackie virus medicine, never major progress, this just causes all treatment measures all to be difficult to viral myocarditis is controlled at incubation period and acute stage.In view of above situation, carry out at the new drug development research of viral myocarditis significant to clinical treatment.
Zhunger Basin does not have YEDOU (Eremosparton.songoricum (Litv) Vass.) and originates in the Xinjiang Junggar Basin, is born in to flow or semifixed sand ground, and rhizome prolongs the elongation of sand ground shallow-layer, reaches 20 meters; On rhizome, sprout new strain, be good pioneer sand-fixation plant.Chrysoeriol (Chrysoeriol), for Zhunger Basin does not have a kind of flavonoid monomeric compound that extraction obtains in the YEDOU, the present research direction at home and abroad of this chemical compound mainly concentrates on the phytochemistry aspect, aspect medical science, does not also have relevant argumentation.But because it belongs to flavone compound, so in some documents, think that it may participate in following physiological regulatory action: effect such as antioxidation, free radical resisting, antibiotic, blood pressure lowering still, does not also have document to mention between itself and the antiviral drugs and has any relation.Aspect non-medical usage, still there is not the correlational study report at present.
Summary of the invention
The purpose of this invention is to provide the application of a kind of flavone monomer in the preparation antiviral drugs.
For achieving the above object, the present invention is by the following technical solutions:
The application of a kind of flavone monomer in the preparation antiviral drugs, this flavone monomer has following chemical structural formula:
Described virus is Picornaviridae virus, comprises Coxsackie virus, enterovirus, rhinovirus, poliovirus and hepatitis A virus.
Described Coxsackie virus is the 3 type Nancy strains of CVB virus.
This laboratory is by finding that to multiple natural plants monomer Selection above-mentioned monomer is inhibited to apoptosis and the virus protease in the viral translation process that virus causes.Because virus finish duplicate with translation process after, must pack, virus can become complete virion, and the protease that virus translation produces has high homology in Picornaviridae (comprising: Coxsackie virus, enterovirus, rhinovirus, poliovirus, hepatitis A virus), and with eukaryotic protease obvious difference.So can conclude this monomer to Picornaviridae after invading cell, all have the effect that suppresses virus maturation, thereby performance suppresses the effect of viral disease progress.
This laboratory has successfully been set up the cell and the animal model of Coxsackie virus infection at present, knows by a series of cytologys and zoopery, and above-mentioned monomer component can obviously suppress the pathological changes that Coxsackie virus causes.
The present invention confirms, this monomer can be used for preparing the especially medicine of micro ribonucleic acid viroid of antiviral, promptly with the effective ingredient of this monomer, make crude drug separately or be aided with the pharmaceutics acceptable auxiliary or carrier is made the preparation that can be applied to organism as medicine.Its preparation can be digestive tract drug-delivery preparation such as tablet, pill, capsule etc.; Also can be injection, as injection, powder pin etc.; Can also be Transdermal absorption drug-delivery preparation, mucosa delivery preparation and respiratory tract administration preparation, as nasal spray etc.The organism here is not limited to the people, also comprises every biology that can be infected by virus especially micro ribonucleic acid viroid such as birds and other mammals.Because the selection of pharmaceutical dosage form is belonged to techniques well known, therefore anyly the dosage form selection that this monomeric this medicinal usage carried out is all belonged to protection scope of the present invention according to guidance of the present invention.
The invention has the beneficial effects as follows: the invention provides a kind of antiviral monomeric compound, through a series of antiviral experiment, prove that this monomer is inhibited to apoptosis and the virus protease in the viral translation process that virus causes, pointing out this monomer is a broad-spectrum antiviral medicament; This monomer is that the picornavirus of representative has tangible antivirus action to Coxsackie virus, for people's Cure Viruses myocarditis provides new selection scheme.
Description of drawings
Fig. 1 is the drug toxicity measurement result figure of SGL-1.
Fig. 2 suppresses the MTT coloration result figure of experiment for CPE.
Observed result figure when the inverted microscope that Fig. 3 suppresses to test for CPE pursues down.
Fig. 4 is the figure as a result of virus breeding inhibition test.
Fig. 5 observes the apoptotic cell figure that engrain takes place down for optical microscope.
Fig. 6 observes the inhibitory action figure of SGL-1 to apoptosis for fluidic cell.
Fig. 7 is for infecting CVB
3The Hela cell after AnnexinV-FITC/PI dyeing, can be observed early apoptosis and late period apoptosis phenomenon figure.
The action diagram that Fig. 8 expresses at the main surface receptor CAR of myocardial cell for RT-PCR method checking SGL-1 downward modulation Coxsackie virus.
Fig. 9 reaches synthetic situation figure as a result for the fracture that detects myocardial cell dystrophin with Western blot method.
The specific embodiment
1, instrument and material
Fusing point is measured with the Boetius micro melting point apparatus; IR utilizes the KBr pressed disc method to go up test at IFS-120H type infrared spectrometer (Germany); FABMS tests on Autospec 3000 mass spectrographs; Nuclear magnetic resonance, NMR INOVA-400 type (Varian company), TMS is interior mark; Column chromatography silica gel (200-300 order), tlc silica gel H are Haiyang Chemical Plant, Qingdao and produce.
Zhunger Basin does not have YEDOU (Eremosparton.songoricum (Litv) Vass.) and picks up from Fuxin, Xinjiang Uygur Autonomous Regions county in JIUYUE, 2002, and being accredited as Zhunger Basin by the Xinjiang desert soil institute Zhang Liyun researcher of the Chinese Academy of Sciences does not have YEDOU (Eremosparton.Songoricum (Litv) Vass.).
2, extract and separate
Zhunger Basin does not have YEDOU (Eremosparton.songoricum (Litv) Vass.) herb dry powder 7.0kg, industrial alcohol merceration three times, each 7 days.Cooling bath gets extractum 555g through concentrating under reduced pressure, and extractum is scattered in the suitable quantity of water, extracts with petroleum ether, ethyl acetate and n-butyl alcohol respectively, gets ethyl acetate part 120g, mixes with 160-200 order silica gel, natural airing, porphyrize.With 200-300 order (1500g) silica gel wet method upper prop, carry out gradient elution for eluent with chloroform-acetone (100: 1～1: 1).TLC monitors, and same composition merges, and gets chrysoeriol 500mg.
3, structure is identified
Chrysoeriol: C
16H
12O
6Yellow powder (methanol); M.p.:320 ℃-322 ℃; FAB-MS m/z:301 (M
+); IRvmar cm
-1: 3420,3164,2996,2972,2843,1624,1572,1509,1471,1380,1314,1283,1243,1132,1099,1024,952,854;
1H-NMR (DMSO-d6) δ: 12.98 (
1H, s, 5-OH), 10.8 (1H, s, 7-OH), 9.98 (1H, s, 4 '-OH), 7.56 (2H, d, J=8.8Hz, H-2 ', H-6 '), 6.92 (2H, m, H-5 ', H-3), 6.51 (1H, d, J=2.4Hz, H-8), 6.36 (1H, d, J=2.0Hz, H-6), 3.89 (3H, s, 1 * CH3); 13C-NMR (DMSO-d6) δ: 164.13 (C-2), 103.21 (C-3), 181.82 (C-4), 161.44 (C-5), 98.84 (C-6), 163.67 (C-7), 94.07 (C-8), 157.33 (C-9), 103.71 (C-10), (120.36 C-1 '), 110.16 (C-2 '), 150.772 (C-3 '), (148.03 C-4 '), (115.74 C-5 '), 121.50 (C-6 '), 56.03 (1 * OMe).And with document contrast, compound identification is 5,7,4 '-trihydroxy-3 '-methoxy flavone (chrysoeriol, Chrysoeriol).
In following examples, replace its title, purity＞99.99% at this breadboard numbering SGL-1 with this compound monomer.
Embodiment 2, drug toxicity are measured
(1), the drug toxicity measurement result of SGL-1:
1, experimental technique: in 96 well culture plates, inoculate myocardial cell; With DMEM doubling dilution medicine, form 6-10 gradient; Every hole adds DMEM doubling dilution medicine 0.1mL, and each dilution factor is provided with 5 multiple holes; Cellular control unit comprises: virus infected cell contrast and space management contrast (if any solvent, then need only add solvent in contrast); Put 37 ℃, 5%CO
2Cultivate 1 week, observation of cell pathological changes (CPE) day by day in the incubator; Calculate half toxic dose (TD in conjunction with MTT dyeing
50), statistical method adopts the Bliss statistical software to analyze.
2, experimental result:
As shown in Figure 1, after three repeated experiments, use the Bliss statistical analysis software, the drug toxicity result who calculates SGL-1 is as follows: TD
50=1.35mg/ml.
(2), the drug toxicity measurement result of ribavirin:
Experimental technique is the same.Experimental result is: TD
50=2.34 μ g/ml.
By the drug toxicity of contrast SGL-1 and ribavirin, the median toxic dose of finding SGL-1 is 577 times of ribavirin, and the toxicity that SGL-1 is described is well below ribavirin.
Embodiment 3, cytopathy (CPE) suppress experiment
(1) CPE of SGL-1 suppresses experiment:
1, experimental technique: with 2 * 10
5The Vero cell inoculation of/ml concentration is in 96 orifice plates, the 0.1ml/ hole; Cultivate formed cell monolayer in 1-2 days after, infect Coxsackie virus (this virus is provided by Concord Hospital of medical university Viral Laboratory, Wuhan, is the 3 type Nancy strains of CVB virus) 10-100TCID
50Medicine to be measured is begun to dilute 8 dilution factors from maximal non-toxic concentration; Infect the back different time, medicine is added cell; Observe CPE progress in microscopically every day, and the record result; When the cell of virus control group approaches all to destroy, stop cell culture; This experiment grouping and the arrangement in 96 orifice plates are as table.
Table 2 suppresses experimental design at the CPE that 96 orifice plates carry out
2, interpretation of result and statistical disposition:
Observe continuously and respectively organize cell CPE in 96 orifice plates and situation occurs, when the most serious experimental group of pathological changes or matched group CPE no longer make progress, begin to do MTT dyeing; Is 10% concentration with serum-free medium with the MTT dilution; Former culture medium is gone in suction, and adds 100ul 10%MTT dye liquor in every hole; Hatched 4 hours for 37 ℃; The MTT dye liquor is removed in suction, washes 1-2 time with PBS, adds DMSO then and reacts with color development stopping; Microplate reader is measured the OD value; Data analysis adopts the Reed-Muench method.
3, experimental result;
(1), calculate medicine SGL-1 by the Reed-Muench method and CVB3 is caused CPE produce 50% concentration that suppresses, below be testing result statistics (table 3) under the inverted microscope;
A situation arises for testing result statistics CPE under table 3 inverted microscope
According to computing formula; (only being higher than 50% infection percentage rate-50)/(only be higher than 50% infection percentage rate-only be lower than 50% infection percentage rate)=(71.4-50)/(71.4-12.5)=0.66; Be added to the drug level dilution index (being 1ug/ml in this experiment) that only is higher than 50% infection rate with 0.66; At last, drawing this viral IC50 is 1.66 μ g/ml.
(2) the MTT coloration result is seen Fig. 2.
Observed result when (3) inverted microscope pursues is down seen Fig. 3.
(2), ribavirin CPE suppresses experimental result:
Experimental technique is the same, IC
50Be 0.24 μ g/ml.
(3), the comparison of SGL-1 and ribavirin Drug therapy index (TI):
1, presses TI=TD
50/ IC
50Calculate, the TI value of SGL-1 is: 1350/1.66=813.25
2, same, the TI value of ribavirin is 2.34/0.24=9.75
By above comparison, can clear and definite SGL-1 median effective dose will be lower than ribavirin, but the safety of SGL-1 will be apparently higher than ribavirin.
1, experimental technique: the prerequisite of this experiment is that CPE suppresses the effect that experiment demonstration medicine has inhibition CVB3 propagation; Collect the cell and the culture fluid of experimental group and matched group; Through multigelation, make the abundant cracking of cell, discharge intracytoplasmic virion; Get supernatant after centrifugal, do 10 times of dilutions of series, establish 8 gradients altogether; Viral liquid after the dilution is inoculated in and has cultivated on Vero cell 96 orifice plates; Contrast infection group and viral infection group and virus+medicine group TCID
50Difference.
2, interpretation of result: calculate infection group and viral infection group culture fluid supernatant inoculation back TCID with the Reed-Muench method
50Calculate virus+medicine group group culture fluid supernatant inoculation back TCID with the Reed-Muench method
50With the dosing group than virus control group TCID
50Reducing by 1 is judged to be more than the logarithm effectively.
3, experimental result: use the calculating of Reed-Muench method and respectively organize TCID
50Value, result as shown in Figure 4, two groups TCID as can be seen
50Drop-out value is all greater than 1.The virus breeding inhibitory action that SGL-1 is described is obvious.
Embodiment 5, relatively at body animal model mortality rate
1, experiment grouping and dosage are determined:
(1), laboratory animal adopts around the Balb/C male mice in age, animal is for the cleaning level, available from animal institute of the Chinese Academy of Medical Sciences.
(2), laboratory animal adopts the randomization group forming criterion to carry out, three drug study groups of the present invention are established in this experiment, establish three matched groups in addition, be respectively: blank group, false matched group and the ribavirin matched group handled, wherein false processing matched group is the viral liquid of lumbar injection isodose, oral medicine lyase of the present invention.(according to the preliminary experiment result, every treated animal number is defined as 18) decided in every treated animal number arrangement according to the statistical result after the trial test.
(2), dosage is determined: medicine high dose group dosage of the present invention is 1250mg/kg; Middle dosage group is according to the 380mg/kg administration.Low dose group: be 126mg/kg, the ribavirin matched group is: 75mg/kg.The false matched group of handling: lumbar injection is irritated the stomach normal saline with the viral suspension of isoconcentration.
2, experimental result: see Table 4.
Table 4 different grouping animal dead rate statistical table
Separation of serum detected index after blood was got in embodiment 6, each grouping of different time
1, virus is at the TCID of Vero cellular level
50Value:
(1), experimental technique: measure TCID
50The method of value suppresses to test identical with virus breeding.
(2), experimental result: each organizes TCID
50The measurement result such as the table 5 of value:
Table 5 is respectively organized TCID
50The measurement result of value
In this testing index, if the TCID50 value can promptly can be thought effective using medicine to descend 1 later on more than the logarithm value.Can judge that from the result of last table SGL-1 has antiviral effect.
2, myocardium enzyme assay in the serum:
(1) test material: instrument is: SABA18 type biochemistry analyzer, reagent are bought from clinical medicine Science ﹠ Technology Center of capital medical university;
(2) test method: test according to biochemistry analyzer and test kit description.
(3) result of the test: myocardium enzyme CK-MB and LDH content all had increase at 3～7 days, but the amplification difference, concrete statistical data such as following table (table 6 and table 7):
Table 6CK-MB statistical data
Table 7LDH statistical data
Result by experiment can find CK-MB and the LDH content in serum along with the increase of infecting natural law, and the meansigma methods electricity rises gradually, but and all there is significant statistical significance in its increasing degree all less than false processed group between 3--7 days.
There are inhibitory action in embodiment 7, SGL-1 to the apoptosis that virus causes
(1), a situation arises for situ end labeling (Tunnel) detection apoptosis:
1, experimental technique: take out six orifice plates and observe down in mirror, notable difference appears in form between each group; PBS gives a baby a bath on the third day after its birth inferior, to remove dead cell and culture medium serum; 4% paraformaldehyde fixed cell 30min with ice-cold new preparation; PBS gives a baby a bath on the third day after its birth inferior; (can be stored in-20 ℃) with 70,75,80,90,95,100% gradient alcohol dehydration; Add the 0.3%H20 methanol solution, room temperature is placed 30min, with the blocking-up endogenous peroxydase; PBS gives a baby a bath on the third day after its birth inferior, adds 0.1%TRITON x-100, ice bath 2min; PBS gives a baby a bath on the third day after its birth inferior, adds 40ul TUNNEL reaction mixture on each coverslip; Incubate for 37 ℃ and bathe 60min; Add 50ul reagent 3 (transformant POD), incubate for 37 ℃ and bathe 30min; PBS gives a baby a bath on the third day after its birth time and to add 50-100ul DAB developer solution, room temperature placement＜30min; PBS gives a baby a bath on the third day after its birth inferior, and is empty dried, mounting.
2, experimental result (Fig. 5): observe apoptotic cell A:(4 * 10 that engrain takes place under the optical microscope), B:(10 * 10); After C:SGL-1 intervened, a situation arises obviously reduces for apoptosis; D: normal cell contrast.Arrow is depicted as the obvious apoptosis cell among the figure.
From Tunnel result, can obviously observe SGL-1 CVB is caused that apoptosis has obvious inhibitory action.
(2), fluidic cell is observed the inhibitory action (Fig. 6, table 8) of SGL-1 to apoptosis:
As shown in Figure 6, A:100TCID50 virus infected cell contrast; B:100TCID50 virus+SGL-1; The contrast of C:SGL-1 medicine; D: normal cell contrast.
The ratio that the influence of table 8 variable concentrations virus cell cycle and apoptosis take place
(3), observe the inhibitory action of SGL-1 by AnnexinV-FITC/PI dyeing to apoptosis:
1, experimental technique: in 6 orifice plates, the cell number of adjusting on the coverslip is 5 * 10 with the Hela cell inoculation
5Be grouped into after 24 hours: viral infection matched group and medicine+viral experimental group; After 12-18 hour, abandon supernatant, it is inferior to give a baby a bath on the third day after its birth with cold PBS; Add Binding Buffer 200 μ l respectively; The Annexin-V (Annexin-V-FITC) that adds 10 μ l Fluorescein isothiocyanate (FITC) labellings, gently behind the mixing, lucifuge room temperature reaction 15 minutes; Add BindingBuffer 300ul again, in 1 hour, use laser scanning co-focusing microscope (LSCM) and detect; Detect preceding 5 minutes and add 2.5 μ l PI dyestuffs; During detection coverslip is taken out, cell places downwards on the microscope slide, finishes a sample during detection and makes the next one again, in order to avoid the influence of smear desiccation is observed.
2, experimental result: as shown in Figure 7, the Hela cell that infects CVB3 after AnnexinV-FITC/PI dyeing, can be observed early apoptosis and late period the apoptosis phenomenon.Apoptotic cells for taking place in the cell that the cell membrane fluorescence green dyes and the nucleus fluorescein is dyed among the figure, and normal cell is without any fluorescence.Figure F is and is subjected to SGL-1 protection and apoptotic cells does not take place.
The influence that embodiment 8, SGL-1 express the myocardial cell surface receptor
1, experimental technique:
(1), extract cell total rna with TRIZOL: supernatant in the Tissue Culture Flask that inclines, and absorb clean as far as possible; Add TRIZOL1.5ml, pressure-vaccum is dissolved among the TRIZOL cell; Get the 0.5ml aforesaid liquid in the 1.5ml centrifuge tube; Add 0.125m l chloroform, concussion mixing 15min, room temperature is placed 3min; Centrifugal: 4 ℃, 12000rpm, 15min; Get supernatant, and be transferred to other centrifuge tube; Add the 0.25ml isopropyl alcohol, room temperature is placed 10min; Centrifugal: 4 ℃, 12000rpm, 5min; Remove supernatant, add 1ml75% ethanol; Centrifugal: 4 ℃, 7500rpm, 5min.Abandon supernatant, drying at room temperature 10min.Add DEPC water dissolution RNA.Electrophoresis is identified the RNA band.
(2), table 9, reaction system:
(3) table 10, loop parameter:
2, experimental result: see Fig. 8.
Coxsackie virus mainly is CAR at the surface receptor of myocardial cell, and this receptor under normal circumstances expression is very low.After CVB3 viral infection myocardial cell, the expression of CAR obviously rises, and has promoted sticking between virus and the myocardial cell.If medicine can be reduced the expression of CAR, the invasion of virus will be reduced.This experiment proves absolutely that by the RT-PCR method SGL-1 has the effect that downward modulation CAR expresses, and then proof SGL-1 can play a role in the stage that penetrates of virus.
Embodiment 9, SGL-1 are to the active influence of virus protease
1, experimental technique:
(1), employing Western blot method detects fracture and the synthetic situation of myocardial cell dystrophin, thereby determines the activity of viral protease 2A and protease 3C.
Western blot method adopts the normal experiment operational approach: myocardial cell cracking → proteinic electrotransfer → sealing → target protein and first antibody react → with second antibody reaction → colour developing.
(2), directly detect virus protease protease 2A activity:
Cultivate former generation neonatal rat myocardial cell, be grouped into: viral infection matched group, normal cell matched group and virus+drug study group.When observing when morphological change occurring between virus control group and the normal cell matched group, stop cell culture, get and infect cellular control unit and virus+drug study group cell, carry out the active detection of virus protease protease 2A, experimental technique and operating procedure are finished by collaboration laboratory.
2, experimental result:
(1), Western blot experimental result, see Fig. 9.
The dystrophin albumen of myocardial cell has a protease cutting site similar to viral capsid proteins, after viral infection enters myocardial cell, dystrophin albumen can be cut into the protein fragments of 220kDa.Find by above experiment, add after the medicine, the phenomenon that dystrophin does not have discovery to be cut, thus confirm that SGL-1 is inhibited to the protease of virus.
(2), virus protease protease 2A activity analysis:
Table 11 assays for protease enzyme activity
By enzyme activity assay, can obviously observe after SGL-1 intervenes, the E.C. 3.4.21.64 CAT/Km index of virus obviously reduces, and illustrates that SGL-1 is inhibited to the protease of virus.The CVB3Nancy strain that experiment is selected for use has universality, and is the main strain that causes a disease of viral myocarditis.The protease that its translation produces has very high homology in Picornaviridae, so study as representative with Coxsackie virus in this research.
The invention provides a kind of antiviral monomeric compound, it originates sufficient, and extraction process is simple.Through a series of antiviral experiment, prove that this monomer is to CVB
3Virus has tangible antivirus action.Virus finish duplicate with translation process after, must pack, can become complete virion, and the protease that virus translation produces has high homology in Picornaviridae (comprising: enterovirus, rhinovirus, poliovirus, hepatitis A virus), and with eukaryotic protease obvious difference.So monomer of the present invention after invading cell, all has the effect that suppresses virus maturation to Picornaviridae, thereby performance suppresses the effect of viral disease progress.
Claims (5)
1. the application of flavone monomer in the preparation antiviral drugs, it is characterized in that: this flavone monomer has following chemical structural formula:
Described virus is Coxsackie virus.
2. the application of a kind of flavone monomer according to claim 1 in the preparation antiviral drugs, it is characterized in that: described application is meant that this flavone monomer is used to prepare antiviral crude drug.
3. the application of a kind of flavone monomer according to claim 1 in the preparation antiviral drugs is characterized in that: described application is meant that this flavone monomer adds pharmaceutics acceptable auxiliary or carrier, is used to prepare antiviral preparation.
4. the application of a kind of flavone monomer according to claim 3 in the preparation antiviral drugs, it is characterized in that: described preparation is digestive tract drug-delivery preparation, injection, Transdermal absorption drug-delivery preparation, mucosa delivery preparation or respiratory tract administration preparation.
5. the application of a kind of flavone monomer according to claim 1 in the preparation antiviral drugs is characterized in that: described Coxsackie virus is the 3 type Nancy strains of CVB virus.
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| CN106377537B (en) * | 2016-08-19 | 2020-07-24 | 江苏康缘药业股份有限公司 | Application of acetyl astragaloside |
| CN113024501B (en) * | 2021-03-30 | 2022-04-22 | 沈阳药科大学 | Polymethoxyflavone derivative with anti-hepatitis A virus activity and preparation method and application thereof |
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| JP2003246792A (en) * | 2002-02-22 | 2003-09-02 | Meiji Milk Prod Co Ltd | Anti-influenza-viral compound |
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2004
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| JPH07277969A (en) * | 1994-04-08 | 1995-10-24 | Souyaku Gijutsu Kenkyusho:Kk | Anti-rs virus agent containing flavone derivative as active component |
| US6217875B1 (en) * | 1997-04-23 | 2001-04-17 | Oryza Oil & Fat Chemical Co., Ltd. | Inhibitors of lipoxygenase |
| JP2000086510A (en) * | 1998-09-16 | 2000-03-28 | Oriza Yuka Kk | Histamine release inhibitor |
| JP2003246792A (en) * | 2002-02-22 | 2003-09-02 | Meiji Milk Prod Co Ltd | Anti-influenza-viral compound |
| CN1389212A (en) * | 2002-07-11 | 2003-01-08 | 江苏正大天晴药业股份有限公司 | Bupleurum flavone composition for resisiting influenza virus and its prepn. |
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| 半枝莲化学成分的研究Ⅱ. 许凤鸣等.中国现代应用药学，第14卷第6期. 1997 * |
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