CN105943529B - Application of the Cichoric acid in the drug of preparation prevention and treatment II type virus infection of dengue fever - Google Patents
Application of the Cichoric acid in the drug of preparation prevention and treatment II type virus infection of dengue fever Download PDFInfo
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- CN105943529B CN105943529B CN201610508441.1A CN201610508441A CN105943529B CN 105943529 B CN105943529 B CN 105943529B CN 201610508441 A CN201610508441 A CN 201610508441A CN 105943529 B CN105943529 B CN 105943529B
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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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
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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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Abstract
The present invention relates to application of the Cichoric acid in the drug of preparation prevention and treatment II type virus infection of dengue fever.Drug described in the application is made of Cichoric acid and medically acceptable auxiliary material, and it is 10%~60% that wherein Cichoric acid, which is used in the mass percentage in drug,.Drug of the present invention has the function of anti-II type dengue fever virus, can be used for preventing and treating dengue infection.
Description
Technical field
The present invention relates to the pharmaceutical products containing organic effective component, and in particular to the drug containing phenolic acid compound.
Background technique
Dengue virus belongs to flaviviridae, Flavivirus in classification.Including 4 different serotypes, i.e., I, II, III, IV type
Dengue virus.In more than 70 a members of flaviviridae, dengue virus is that epidemic regions are most wide, morbidity is most, harm is biggish
A kind of arboviruse, main communication media are Aedes aegypti and aedes albopictus, and dengue virus infection is mostly in the torrid zone and Asia heat
The popular outburst in band area.Dengue fever is caused by dengue virus (dengue virus, DV), not according to clinical manifestation severity
Together, it is divided into dengue fever (DF), dengue hemorrhagic fever (DHF), dengue shock syndrome (dengue shock syndrome, DSS) three
Kind Clinical types.According to the statistics of the World Health Organization, the whole world has 500,000 people to infect dengue fever every year, dead about 2.5 ten thousand people, about
Hundred million population of 25-30 is under the threat of dengue virus.Dengue fever is also one of the infectious disease of Guangzhou emphasis prevention and control, and 2014
Large-scale outbreak of epidemic occurs for Guangzhou province, and epidemic situation presentation generation is early, diffusion is fast, involves the features such as range is wide.Guangzhou according to statistics
City's annual report case load is 3 times of nearly 20 years accumulative case report cases, and Chaozhou Epidemic Situation of Dengue Fever in 2015 is also more tight
Weight.Dengue epidemic in Guangdong Province epidemic situation in 2014 adds up reported cases and is cured more than 40,000 people, and explosively demand height daily detects in disease control department
Up to thousands of parts.The disease has seriously affected the health and socio-economic development of the city the Liao Wo people.Due to there is no Dengue at present
Hot vaccine also lacks corresponding antiviral drugs, how to cope with this emerging infectious disease have become medicine sector need reply
Key subjects.
Cichoric acid is a kind of water-soluble phenolic compounds extracted from the dry herb of compositae plant witloof, and molecular formula is
C22H18O12, fusing point is 206 DEG C, and optical activity is+383.5 ° of [α] (MeOH, C:1.555mol/l), density: 1.641g/cm3.Easily
It is dissolved in ethyl alcohol, methanol, dioxanes and acetone, is slightly soluble in ethyl acetate and ether, does not dissolve in benzene and chloroform.It is readily soluble in the hot water, but
When temperature is 20 DEG C, only 0.5% is solvable.Have the function of anti-inflammatory, enhancing immune function and induce cell apoptosis, and can press down
Hyaluronidase processed protects the influence of free radical of the collagen from can lead to degradation, to diabetes, hyperlipidemia, artery congee
Sample sclerosis, hyperuricemia and fatty liver etc. have improvement result.As a kind of noncompetitive, reversible mutual with amino acid
The integrase inhibitor of effect, Cichoric acid has the effects that inhibit inhibition of HIV, anti-inflammatory, antiviral, anticancer, antimycotic, especially right
Virus has preferable selectivity.But there are no the active report of Cichoric acid anti-dengue virus occur in document report at present
Road.
Summary of the invention
The technical problem to be solved in the present invention is to provide the new applications of Cichoric acid, i.e., the new opplication in pharmacy.
The above-mentioned new opplication in pharmacy is Cichoric acid answering in the drug of preparation prevention and treatment II type virus infection of dengue fever
With, wherein shown in the chemical structure of the Cichoric acid such as following formula (I):
In above-mentioned application, the Cichoric acid 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 Cichoric acid and medically acceptable auxiliary material, wherein Cichoric acid is in medicine
Mass percentage in object is 10%~60%.
In above-mentioned application, the drug can be clinically acceptable injection, capsule or tablet.
Injection, capsule and tablet of the present invention have the function of anti-II type dengue fever virus, can be used for preventing and treating
Dengue infection.
The present invention is using cytopathic-effect inhibition assay measurement Cichoric acid to II type of dengue fever with Cichoric acid anti-dengue virus
The inhibiting effect of virus observes toxic effect of the Cichoric acid to BHK-21 cell and the inhibiting effect to dengue fever II type virus,
Toxic concentration (the CC of half for measuring test medicine using CCK-8 detection reagent50) it is 714.9, half maximal effect concentration
(EC50) it is 8.19, selecting index SI is 87.29, efficiently for low toxicity.It is described that specific experimental method is as follows.
1. experimental material
1.1 cell strain cream hamster kidney cells (BHK-21), quoted from Wuhan institute of viruses, T11 generation.This room freezes conservation.
1.2 experimental groups and its corresponding test medicine
Given the test agent: taking the Cichoric acid for being purchased from Shanghai Yuan Ye Biotechnology Co., Ltd (LOT:P29N3R1), and addition contains
The DMEM culture medium of 0.5%DMSO dissolves, and the medical fluid of every milliliter of 0.85mg containing Cichoric acid is made.
1.3 Strain Dengue, two type virus is quoted from Wuhan institute of viruses
1.3 reagents and instrument newborn calf serum and DMEM culture medium (Gibco company)；DMSO (Guangzhou Kang Yang chemical industry
Co., Ltd)；Trypsase (DIFCO company of the U.S.；Shanghai Sheng Gong bio-engineering corporation agency).Olympus PM-6 is inverted aobvious
Micro mirror (Japanese OLYMPUS company)；；E-52AA Rotary Evaporators (Shanghai Yarong Biochemical Instrument Plant)；BP221S electronic analysis day
Flat (Shanghai precision instrument table Co., Ltd).
2. method
The measurement of 2.1 Cichoric acids toxic concentration on BHK-21 cell
It is 0.5 × 10 by density5Cell/ml BHK-21 cell inoculation is in 96 porocyte culture plates, every 100 μ L of hole.It is raw
Long cell for 24 hours is adherent rear spare in flakes (80-90%).By drug with cell maintenance culture solution (contain 2% serum) from continuous 2 times of ladders
Degree 6 gradients of dilution, prepared 100 μ L of medical fluid is added in every hole, if normal cell controls, every hole is added 100 μ L cells and maintains
Culture solution.If solvent control group, in 37 DEG C of 5%CO2It is cultivated in incubator.It is added after dosing culture 48h and contains 100 μ L 10%
The culture medium of CCK-8 reagent, in 37 DEG C of incubation 1h.It is calculated according to following method:
Absorbance is detected with 450nm, drug indicates the toxicity of cell with the activity of cell, calculation formula:
Cell viability (%)=(medicine group-blank control)/(cell controls-blank control) × 100%.
The measurement of 2.2 viral suppressions
Selection grows vigorous, layered good cell, and pancreatin digestion is added in tipping growth-promoting media, makes cell with growth-promoting media dispersion
Suspension concentration is 105A/hole.Cell suspension is added in 96 orifice plates with pipettor, every hole 100uL.Culture plate is placed in culture
It is cultivated 12~18 hours in case, after cell grows up to single layer in 96 orifice plates, sucks culture solution, the difference of 100ul is added in every hole
The drug of diluted concentration and the 100TCID of 100uL50Virus liquid, 3 multiple holes are arranged in each drug concentration, while blank pair is arranged
It according to group, normal cell controls group, virus control group and positive controls, is placed in incubator and is incubated for 1h, suck drug containing culture solution
And virus liquid.Maintaining liquid is sucked in virus control group 75%-100% lesion, 100 μ L 10%CCK-8 is added, in microplate reader
450nm measures absorbance, calculates the viral suppression of drug.
Viral suppression=(test group mean OD value-virus control group mean OD value)/(cell controls group mean OD value-
Virus control group mean OD value) × 100%
3. result
3.1 drug toxicity results see the table below 1.
Table 1
3.2 drugs see the table below 2 to the measurement result of viral suppression.
Table 2
It is above-mentioned the experimental results showed that extract of the present invention has obvious inhibiting effect to two type virus of Dengue.Select index
Greater than 2, it can be used for preparing the treatment and prevention drug of dengue fever.
Specific embodiment
Example 1:(injection)
Cichoric acid 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)
Take Cichoric acid 5000mg and 4000mg microcrystalline cellulose, 500mg sodium carboxymethyl starch, 400mg dodecyl sulphate
The auxiliary materials such as sodium are sufficiently mixed, and are carried out dry granulation using roll-in method, then mix with appropriate magnesium stearate, are packed into the hollow glue of 3#
Capsule is made the capsule that specification is 100mg/ and supplies to be administered orally.
Example 3:(tablet)
It takes Cichoric acid 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.
Claims (3)
1. application of the Cichoric acid as sole active agent in the drug of preparation prevention and treatment II type virus infection of dengue fever, wherein
Shown in the chemical structure of the Cichoric acid such as following formula (I):
2. application according to claim 1, it is characterised in that: the drug is by Cichoric acid and medically acceptable auxiliary
Material composition, it is 10%~60% that wherein Cichoric acid, which is used in the mass percentage in drug,.
3. application according to claim 2, characterized in that the drug is injection, capsule or tablet.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610508441.1A CN105943529B (en) | 2016-06-29 | 2016-06-29 | Application of the Cichoric acid in the drug of preparation prevention and treatment II type virus infection of dengue fever |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610508441.1A CN105943529B (en) | 2016-06-29 | 2016-06-29 | Application of the Cichoric acid in the drug of preparation prevention and treatment II type virus infection of dengue fever |
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| CN105943529B true CN105943529B (en) | 2018-12-18 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103497192A (en) * | 2008-12-09 | 2014-01-08 | 吉里德科学公司 | Modulators of TOLL-like receptors |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103497192A (en) * | 2008-12-09 | 2014-01-08 | 吉里德科学公司 | Modulators of TOLL-like receptors |
Non-Patent Citations (2)
| Title |
|---|
| STRATEGIES IN THE DESIGN OF ANTIVIRAL DRUGS;Erik De Clercq;《REVIEWS》;20020131;第1卷;13-25 * |
| 菊苣的药理药效研究进展;孙博喻等;《中华中医药学刊》;20150731;第33卷(第7期);1577-1579 * |
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