CN103120661A - Application of Eryngiolide A in medicine for resisting influenza A virus - Google Patents
Application of Eryngiolide A in medicine for resisting influenza A virus Download PDFInfo
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- CN103120661A CN103120661A CN 201210412009 CN201210412009A CN103120661A CN 103120661 A CN103120661 A CN 103120661A CN 201210412009 CN201210412009 CN 201210412009 CN 201210412009 A CN201210412009 A CN 201210412009A CN 103120661 A CN103120661 A CN 103120661A
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- eryngiolide
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Abstract
The invention discloses an application of Eryngiolide A in preparation of a medicine for resisting influenza A virus. Experiments prove that the influenza A virus has outstanding inhibiting effect on an influenza A virus fluA, so that the potential application value of the Eryngiolide A in the field of treatment of influenza A virus infectious diseases is prompted. The application of the Eryngiolide A in preparation of the medicine for treating influenza virus infection is firstly disclosed because a skeleton type belongs to a fire-new skeleton type and the inhibitory activity of the Eryngiolide A on an influenza virus is inconceivably high; and the Eryngiolide A has outstanding substantiality characteristic without possibility of any inspiration given by other compounds and obviously achieves the outstanding progress by being used for preventing and treating influenza virus infection.
Description
Technical field
The present invention relates to the application of Eryngiolide A in the medicine of preparation anti-influenza A virus (Influenza A virus, Flu-A).
Background technology
Flu A belongs to Orthomyxoviridae, at the mankind and other biological, among a small circle popular is arranged every year, causes that upper respiratory system infects.When being very popular, can cause serious respiratory system infection, very the person causes that pneumonia, encephalitis are even dead.
the compd E ryngiolide A that the present invention relates to is one and delivered (Wang in 2012, S. J. et al., 2012. Eryngiolide A, a Cytotoxic Macrocyclic Diterpenoid with an Unusual Cyclododecane Core Skeleton Produced by the Edible Mushroom Pleurotus eryngii. Organic Letters 14 (14), 3672 – 3675.) New skeleton compound, this compound has brand-new framework types, present purposes only relates to the cytotoxic activity (Wang of cancerous cell, S. J. et al., 2012. Eryngiolide A, a Cytotoxic Macrocyclic Diterpenoid with an Unusual Cyclododecane Core Skeleton Produced by the Edible Mushroom Pleurotus eryngii. Organic Letters 14 (14), 3672 – 3675.), belong to open first for the purposes of the Eryngiolide A that the present invention relates in preparation treatment influenza infection medicine, because framework types belongs to brand-new framework types, and it suppresses active unexpectedly strong for influenza virus, there is not the possibility that is provided any enlightenment by other compounds, possesses outstanding substantive distinguishing features, the control that is used for simultaneously influenza infection obviously has significant progress.
Summary of the invention
For above-mentioned prior art, the invention provides the new purposes of Eryngiolide A in pharmacy: the application of Eryngiolide A in the medicine of the anti-Flu A of preparation.
The experiment proved that, Eryngiolide A all has significant inhibitory action to flu A: suppress Flu A and at MDCK, CPE occurs, IC
50Be 2
-10.58, TI is 588.16.
Eryngiolide A has significant inhibitory action to influenza A virus, and the clinical influenza a virus infection disease that is used for the treatment of of this prompting Eryngiolide A provides experimental basis, has important reference value.
Described compd E ryngiolide A structure is as shown in formula I:
Formula I
The purposes of the Eryngiolide A that the present invention relates in preparation treatment influenza infection medicine belongs to open first, because framework types belongs to brand-new framework types, and it suppresses active unexpectedly strong for influenza virus, there is not the possibility that is provided any enlightenment by other compounds, possess outstanding substantive distinguishing features, the control that is used for simultaneously influenza infection obviously has significant progress.
In order to understand better essence of the present invention, the present invention is further illustrated below in conjunction with embodiment.
The specific embodiment
The preparation method of compd E ryngiolide A involved in the present invention is referring to document (Wang, S. J. et al., 2012. Eryngiolide A, a Cytotoxic Macrocyclic Diterpenoid with an Unusual Cyclododecane Core Skeleton Produced by the Edible Mushroom Pleurotus eryngii. Organic Letters 14 (14), 3672 – 3675.).
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not subjected to any restriction of specific embodiment, but limited by claim.
Embodiment 1: the preparation of compd E ryngiolide A tablet involved in the present invention:
Get 20 and digest compound Eryngiolide A, add conventional adjuvant 180 grams that prepare tablet, mixing, conventional tablet machine are made 1000.
Embodiment 2: the preparation of compd E ryngiolide A capsule involved in the present invention:
Get 20 and digest compound Eryngiolide A, add the conventional adjuvant such as starch 180 grams that prepare capsule, mixing is encapsulatedly made 1000.
Further illustrate its pharmaceutically active below by pharmacodynamic experiment.
Experimental example: the effect research of Eryngiolide A to influenza A virus:
(1) cell strain and Strain: Madin-Darby canine kidney(cell line) (MDCK) (MDCK, influenza virus sensitive cells) is drawn from Chinese CDC virosis institute; Influenza virus A type (Flu A) 1995.AII:32094 strains draws from Chinese CDC virosis institute.
(2) cytotoxic assay:
Reference literature (Wang Shouchuan, Wang Lin, old superfine, the experimentation of oral liquid for clearing away lung-heat Contained Serum to viral inhibition, Nanjing University of Traditional Chinese Medicine's journal, 2008; 24(1): method 25 ~ 27), each sample is done serial dilution (2 with 2 multiple proportions
-1 ~-5), then be inoculated on MDCK in 96 plate holes by the dilution sequential lateral, every hole 100uL, every dilution factor vertically repeat 3 holes (A, B, C capable), parallel 1 ~ 6 hole of establishing microwell plate D is the cell contrast, 7 ~ 12 holes not inoculating cell are blank, and microscopically is observed CPE, Continuous Observation 7d every day, neutral red staining, measure the OD value at the 540nm wavelength, experimental group is compared the calculating cell survival rate with cell matched group OD value, calculate medicine half cytotoxic concentration (TD with the Reed-Muench method
50).
(3) toxin inhibitory test:
Reference literature (Wang Shouchuan, Wang Lin, old superfine, the experimentation of oral liquid for clearing away lung-heat Contained Serum to viral inhibition, Nanjing University of Traditional Chinese Medicine's journal, 2008; 24(1): method 25 ~ 27), sample is inoculated on cell monolayer in 96 plate holes by the dilution sequential lateral, every hole 100uL, every dilution factor vertically repeat 4 holes, and the A of microwell plate, B, C capable adding, contain 100 TCID
50Viral 100uL as test group, D is capable, and the capacity cell maintenance medium that replenish to wait is the contrast of variable concentrations medicine, the parallel F that establishes is capable of virus control, what E was capable 1 ~ 12 contrasts as cell.37 ℃, 5%CO
2Cultivate, observe CPE every day, Continuous Observation 4d.When 90% above CPE appears in virus control, add 1% neutral red staining, read the A value with microplate reader at wavelength 540nm wavelength, each is organized the A value and removes virus control group A value, each test group is compared with cell control group A value, obtained cell survival rate, calculate half with the Reed-Muench method and press down malicious concentration (IC
50), TD the most at last
50And IC
50Compare and obtain to press down malicious index (TI).
(4) result:
1. sample TD
50Mensuration: the cellular control unit microscopically observes that adherent growth is fine and close, form is good.The TD of Eryngiolide A
50Be respectively 2 at MDCK
-1.38
2. press down the poison experiment: the adherent densification of cellular control unit, form are good.Microscopic observation finds, Flu A MDCK CPE with refractivity strengthen, downright bad, be broken for principal character.
And toxin inhibitory test is respectively organized cell, and according to the diluted sample gradient, it is fully protected that CPE:FluA-MDCK group cell cell before the 8th dilution factor appears in the gradient rule, CPE occurs afterwards, and CPE reduces with sample concentration and increases the weight of gradually.
With above-mentioned brassboard with 1% neutral red staining, survey the A value of 450nm with microplate reader, after each was organized the A value and cuts virus control group A value, each experimental group A value was compared acquisition IC with cell control group A value
50, IC
50With TD
50Compare and obtain TI: suppress Flu A and at mdck cell, CPE occurs, IC
50Be 2
-10.58, TI is 588.16.
Conclusion:Eryngiolide A has very strong inhibitory action to influenza A virus, and safety, so Eryngiolide A has application background widely in treatment influenza a virus infection disease.
Claims (1)
1.Eryngiolide the application of A in the medicine of anti-influenza A virus, described compd E ryngiolide A structure as
Formula IShown in:
Formula I.
Priority Applications (1)
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CN 201210412009 CN103120661A (en) | 2012-10-25 | 2012-10-25 | Application of Eryngiolide A in medicine for resisting influenza A virus |
Applications Claiming Priority (1)
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CN 201210412009 CN103120661A (en) | 2012-10-25 | 2012-10-25 | Application of Eryngiolide A in medicine for resisting influenza A virus |
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CN103120661A true CN103120661A (en) | 2013-05-29 |
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Application publication date: 20130529 |