CN109453158A - Application of the baicalein in the drug of preparation prevention and treatment zika virus infection - Google Patents
Application of the baicalein in the drug of preparation prevention and treatment zika virus infection Download PDFInfo
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- CN109453158A CN109453158A CN201811328473.9A CN201811328473A CN109453158A CN 109453158 A CN109453158 A CN 109453158A CN 201811328473 A CN201811328473 A CN 201811328473A CN 109453158 A CN109453158 A CN 109453158A
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- baicalein
- drug
- zika virus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
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Abstract
The present invention relates to application of the baicalein in the drug of preparation prevention and treatment zika virus infection, drug described in the application is made of baicalein and medically acceptable auxiliary material, and it is 0.1%~95% that wherein baicalein, which is used in the mass percentage in drug,.Drug of the present invention is used to prevent and treat the significant effect of zika virus infection.
Description
Technical field
The present invention relates to the pharmaceutical products containing organic effective component, and in particular to the drug containing flavone compound.
Background technique
Zika virus (Zika virus, ZIKV) is a kind of mosquito matchmaker flavivirus, mainly bites propagation by Aedes aegypti,
It by mother and baby, blood and can spread through sex intercourse, crowd is generally susceptible.It can cause the light symptoms of similar dengue fever, can not also at present
It is prevented and treated by drug or vaccine.So far, existing more than the 30 countries report zika virus in the whole world infects and causes multiple countries
Introduced cases.The World Health Organization (WHO) thinks that newborn's microcephalus, actue infectious polyradiculoneuritis may be with zika virus
There is association in infection.Fetus is infected via pregnant woman, and then leads to the microcephalus of ewborn infant；The general table of Adult infections' virus
It is now fever (rare high fever, usually low-heat), maculopapule, arthralgia, the conjunctivitis of apyetous, it is serious to can lead to paralysis
And death.For the first time in Western Pacific Mi Keluoni subgroup island eruption and prevalence, 2013-2014 was in Oceanian method in 2007 for the virus
Belong to Polynesia and broken out more massive primary prevalence, arises from Central and South America within 2015 and quickly spread, 2016, the world defended
Raw tissue (WHO) holds an emergency meeting, and announces zika virus being classified as global emergency public health event, and appeal international community
Coordination.Present Global You Jin30Ge research institution is carrying out zika virus vaccine research and development, but the people not ratified still uses
Vaccine, the drug for finding a kind of effectively treatment zika virus disease is extremely urgent, and research zika virus is the current research of virology
Hot spot.
Baicalein, category flavone compound, yellow crystal, 264 DEG C -265 DEG C of fusing point.It is dissolved in methanol, ethyl alcohol, acetone, vinegar
Acetoacetic ester and hot glacial acetic acid, are slightly soluble in chloroform, and being dissolved in dilute sodium hydroxide is in green brown, but unstable, oxidizable at green.
Shown in the chemical structure of baicalein such as following formula (I):
Baicalein is rich in the root plant radix scutellariae (Scutellaria baicalensis Georgi), and baicalein is radix scutellariae
One of middle highest flavone compound of content.Since baicalein is primarily present in radix scutellariae, and gain the name.Baicalein has drop
Low cerebral vascular resistance, the effect for improving brain blood circulation, increasing cerebral blood flow (CBF) and anti-platelet aggregation, after being clinically used for cerebrovascular disease
The treatment of paralysis.But there are no baicalein occur with the active report of anti-zika virus in document report at present.
Summary of the invention
The technical problem to be solved in the present invention is to provide the new applications of baicalein, i.e., the new opplication in pharmacy.
The above-mentioned new opplication in pharmacy is application of the baicalein in the drug of preparation prevention and treatment zika virus infection.
In above-mentioned application, the baicalein can be using conventional method from extracted form natural plant, can also be by synthesizing
Or other methods are made.
In above-mentioned application, the drug is made of baicalein and medically acceptable auxiliary material, wherein baicalein is in medicine
Mass percentage in object is 0.1%~95%.
In above-mentioned application, the drug can be clinically acceptable high-capacity injection, injection, capsule,
Granule or tablet.
The present invention, to the inhibiting effect of zika virus, observes baicalein pair using virus plaque titre method measurement baicalein
The toxic effect of Vero cell and inhibiting effect to zika virus, the half of test medicine is measured using CCK-8 detection reagent
Toxic concentration (CC50) it is 43.3 μM, to the ceiling effect concentration (EC of half zika virus50) it is 0.1 μM, select index SI
It is 433 respectively, illustrates that baicalein has the advantages that low toxicity is efficient for preventing and treating zika virus infection.
Said effect is verified below by way of zoopery.
1. experimental material
1.1 cell strain
African green monkey kidney cell (Vero) is purchased from the American Type Culture Collection committee, Chinese Academy of Sciences cell bank, this experiment
Room saves.
1.2 experimental groups and its corresponding test medicine
Given the test agent: the baicalein for being purchased from Baoji time Biotechnology Co., Ltd (Lot:0151024) is taken, PBS is used
The stock solution that concentration is 5mM is made.
1.3 Strain
Zika Vrius(GenBank accession KU963796)
From Guangdong Prov. Disease Prevention-control Center, ZV plants expand in C6/36 cell, and supernatant passes through 0.45 μm of micropore
- 80 DEG C are stored in after membrane filtration.Virus titer is by plaque assay in Vero raji cell assay Raji.
1.4 reagents and instrument newborn calf serum and DMEM culture medium (Gibco company)；DMSO (Sigma company)；Pancreas egg
White enzyme (DIFCO company, the U.S.).Olympus PM-6 inverted microscope (Japanese OLYMPUS company).
2. method
The measurement of 2.1 baicaleins toxic concentration on Vero cell
The Vero grown in flakes in cell bottle is digested with EDTA- pancreatin and is counted, with 2 × 104/ 100 hole μ l/ inoculating cells
In 96 orifice plates (white flat bottom), 37 DEG C of 5%CO2It is incubated overnight.Drug is pressed with cell grown cultures liquid (containing 10% serum)
100,50,25,10,5,1,0.1,0.01 μM of final concentration dilutions.Culture medium is sucked, 10 μ l of drug solution is added in every hole, if normally
90 μ l cell grown cultures liquid are added in cell controls, every hole.Then volume fraction is added to every hole is 10%CCK8 cell activity
Detection reagent (wherein the ratio of DMEM and CCK8 reagent be 9:1) 100 μ L, tissue culture plate set 37 DEG C, volume fraction be 5%
Continue to be incubated for 20min in CO2 incubator.Each hole absorbance value, Detection wavelength 450nm are measured in microplate reader.Cell survival rate
Calculation formula:
Cell survival rate (%)=(medicine group-blank control)/(normal cell group-blank control) × 100%
Calculating 50% toxic concentration is the toxic concentration (CC of drug half50)
The measurement of 2.2 antiviral effect in vitro
50mM mother liquid medicine is configured to sterile PBS.The same 1.3.1 of cytotoxicity experiment.By Vero, Hela, Huh7, BHK-
21 cells are equably seeded in 96 porocyte culture plates, grow to 4 × 10 to cell4Serum-free is replaced with when a/hole
Final concentration of 25.0,17.5,10.0,5.0,1.0,0.1,0.01 μM of DMEM culture medium gradient dilutions are added in DMEM culture medium
Drug to be measured, 37 DEG C of cell incubators are incubated for 1h.Infection multiplicity (multiplicity of is added in every hole after incubation
Infection) the zika virus of MOI=0.5,37 DEG C of cell incubators adsorb 1h.Virus liquid is discarded, it is primary with PBS rinse, add
Enter pastille culture medium, 37 DEG C of cell incubator culture 48h.It collects cell supernatant and measures virus titer.Calculate 50% virus suppression
Concentration processed is drug medium effective concentration (EC50)
Select index SI=CC50/EC50
The measurement of 2.3 virus titers
The Vero grown in flakes in cell bottle is digested with EDTA- pancreatin and is counted, with 2 × 105/ 500 hole μ l/ inoculating cells
In 24 orifice plates.37 DEG C of 5%CO2It is incubated overnight.Virus Sample is diluted with the culture medium without serum, two dilutions times are set
Two multiple holes, extension rate: 10 is arranged in number, each extension rate-2-10-7.Culture medium is sucked, every hole adds 200 μ l virus liquids, in
37 DEG C of 5%CO2 cultivate 1h.Inoculum is removed, every hole adds 0.8%CMC, 37 DEG C 5%COs of the 500 μ l containing 2% serum2Cultivate 5-
9 days.It is fixed with 3.7% paraformaldehyde, 0.5% violet staining, counts plaque.Pfu/ml=plaque number × 1000/200 × dilute
Release the inverse of the factor.
3. result
3.1 drug toxicity results see the table below 1.
1 baicalein of table is to Vero cytotoxicity
It is drawn using software GraphPad Prism5.0 as shown in Figure 1.
As seen from Figure 1, CC of the baicalein in the drug toxicity of Vero cell50It is=43.4 μM, is low cytotoxicity drug.
The measurement result of 3.2 Antiviral Effects effect see the table below 2 and Fig. 2.
Inhibiting effect of 2 baicalein of table to zika virus
Baicalein is measured in the antivirus action of Vero cell through virus titer, the EC that is calculated50It is 0.1 μM, table
Bright baicalein has the selection index SI=433 of anti-zika virus, there is preferable antivirus action and safety.
Detailed description of the invention
Fig. 1 is contamination Vero cell survival rate and baicalein concentration relationship curve.
Fig. 2 is curve graph of the baicalein to zika virus inhibiting effect.
Specific embodiment
Example 1:(injection)
Baicalein 1000mg is taken, citric acid 1000mg, sodium citrate 500mg are added, sodium chloride 1800mg adds the note of 1000ml
It penetrates and uses water, be stirred to dissolve, the note of every 2mg/2ml is made through 100 DEG C of 15 minutes flowing steam sterilizations in degerming filtration, encapsulating
Liquid is penetrated to use for injection.
Example 2:(capsule)
Baicalein 5000mg is taken, dry granulation is carried out using roll-in method, is packed into 3# Capsules, specification, which is made, is
100mg/ capsules are for being administered orally.
Example 3:(tablet)
It takes baicalein 5000mg to be uniformly mixed with 4000mg starch, 200mg cross-linked pvp, 300mg sodium carboxymethyl starch, uses
75% ethanol solution of 5%PVP is pelletized as adhesive, softwood processed with 18 meshes, 1h after 60 DEG C of dryings, is added after 20 mesh whole grains
Enter appropriate talcum powder, mix, tabletting, the tablet that specification is 100mg/ piece is made and supplies to be administered orally
Example 4:(granule)
It takes baicalein 5000mg to be uniformly mixed with 4000mg starch, 200mg cross-linked pvp, 300mg sodium carboxymethyl starch, uses
75% ethanol solution of 5%PVP is as adhesive, and softwood processed, with the granulation of 18 meshes, 1h after 60 DEG C of dryings, specification, which is made, is
The particle of 100mg/ piece is for being administered orally.
Example 5:(high-capacity injection)
Baicalein 100mg, sodium chloride 900mg is taken to add the water for injection of 1000ml, be stirred to dissolve, degerming filtration fills
Envelope, through 100 DEG C of 15 minutes flowing steam sterilizations, the injection that every 0.1mg/1ml is made is used for injection.
Claims (3)
1. application of the baicalein in the drug of preparation prevention and treatment zika virus infection.
2. application according to claim 1, it is characterised in that: the drug is by baicalein and medically acceptable auxiliary
Material composition, it is 0.1%~95% that wherein baicalein, which is used in the mass percentage in drug,.
3. according to application described in right 2, which is characterized in that the drug be high-capacity injection, injection, capsule,
Granule or tablet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811328473.9A CN109453158A (en) | 2018-11-09 | 2018-11-09 | Application of the baicalein in the drug of preparation prevention and treatment zika virus infection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811328473.9A CN109453158A (en) | 2018-11-09 | 2018-11-09 | Application of the baicalein in the drug of preparation prevention and treatment zika virus infection |
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| Publication Number | Publication Date |
|---|---|
| CN109453158A true CN109453158A (en) | 2019-03-12 |
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ID=65609806
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811328473.9A Pending CN109453158A (en) | 2018-11-09 | 2018-11-09 | Application of the baicalein in the drug of preparation prevention and treatment zika virus infection |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107823215A (en) * | 2017-12-16 | 2018-03-23 | 广州中医药大学 | Application of the scutelloside in the medicine for preparing preventing and treating zika virus infection |
-
2018
- 2018-11-09 CN CN201811328473.9A patent/CN109453158A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107823215A (en) * | 2017-12-16 | 2018-03-23 | 广州中医药大学 | Application of the scutelloside in the medicine for preparing preventing and treating zika virus infection |
Non-Patent Citations (3)
| Title |
|---|
| HASSANDARVISH POUYA等: "In silico study on baicalein and baicalin as inhibitors of dengue virus replication", 《RSC ADVANCES》 * |
| JIAN LEI等: "Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor", 《SCIENCE》 * |
| SONAM BHARGAVA 等: "Identification of structural requirements and prediction of inhibitory activity of natural flavonoids against Zika virus through molecular docking and Monte Carlo based QSAR Simulation", 《NATURAL PRODUCT RESEARCH》 * |
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Application publication date: 20190312 |
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