CN102988350A - Application of Aphanamixoid A in influenza A virus (Flu-A) resistant medicine - Google Patents
Application of Aphanamixoid A in influenza A virus (Flu-A) resistant medicine Download PDFInfo
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- CN102988350A CN102988350A CN2012104688755A CN201210468875A CN102988350A CN 102988350 A CN102988350 A CN 102988350A CN 2012104688755 A CN2012104688755 A CN 2012104688755A CN 201210468875 A CN201210468875 A CN 201210468875A CN 102988350 A CN102988350 A CN 102988350A
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Abstract
The invention discloses application of Aphanamixoid A in an influenza A virus (Flu-A) resistant medicine. Experiments prove that Aphanamixoid A has obvious inhibitory effect on Flu-A, which prompts that Aphanamixoid A has potential application value in the field of treating Flu-A infectious diseases. The application of Aphanamixoid A for preparing the medicine for treating influenza virus infection is disclosed for the first time; because the skeleton type belongs to a brand new skeleton type and the Flu-A inhibitory activity of Aphanamixoid A is strong unexpectedly, the possibility that other compounds give any inspiration does not exist; Aphanamixoid A has outstanding substantive characteristics; and simultaneously, Aphanamixoid A has obvious progress for preventing and treating influenza virus infection.
Description
Technical field
The present invention relates to the application of Aphanamixoid A in the medicine of preparation anti-influenza A virus (Influenza A virus, Flu-A).
Background technology
Flu A belongs to Orthomyxoviridae, at human and other biological among a small circle popular is arranged every year, causes the upper respiratory system infection.When being very popular, can cause serious respiratory system infection, very the person causes pneumonia, encephalitis even death.
The compd A phanamixoid A that the present invention relates to is one and delivered (Cai in 2012, J. Y. et al., 2012. Aphanamixoid A, a Potent Defensive Limonoid, with a New Carbon Skeleton from Aphanamixis polystachya. Organic Letters 14 (10), 2524 – 2527.) New skeleton compound, this chemical compound has brand-new framework types, present purposes only relates to insect antifeedant activity (Cai, J. Y. et al., 2012. Aphanamixoid A, a Potent Defensive Limonoid, with a New Carbon Skeleton from Aphanamixis polystachya. Organic Letters 14 (10), 2524 – 2527.), belong to open first for the purposes of the Aphanamixoid 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 chemical compounds, possess 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 Aphanamixoid A in pharmacy: the application of Aphanamixoid A in the medicine of the anti-Flu A of preparation.
The experiment proved that Aphanamixoid A all has significant inhibitory action to flu A: suppress Flu A and at MDCK CPE occurs, IC
50Be 2
-9.27, TI is 265.03.
Aphanamixoid 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 Aphanamixoid A provides experimental basis, has important reference value.
Described compd A phanamixoid A structure is shown in formula I:
Formula I
The purposes of the Aphanamixoid 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 chemical 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 A phanamixoid A involved in the present invention is referring to document (Cai, J. Y. et al., 2012. Aphanamixoid A, a Potent Defensive Limonoid, with a New Carbon Skeleton from Aphanamixis polystachya. Organic Letters 14 (10), 2524 – 2527.).
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 A phanamixoid A tablet involved in the present invention:
Get 20 and digest compound Aphanamixoid A, add conventional adjuvant 180 grams of preparation tablet, mixing, conventional tablet machine are made 1000.
Embodiment 2: the preparation of compd A phanamixoid A capsule involved in the present invention:
Get 20 and digest compound Aphanamixoid A, add conventional adjuvant such as starch 180 grams of preparation capsule, mixing is encapsulatedly made 1000.
Further specify its pharmaceutically active below by pharmacodynamic experiment.
Experimental example: Aphanamixoid A studies the effect of 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:
(old superfine, the oral liquid for clearing away lung-heat Contained Serum is to the experimentation of viral inhibition, Nanjing University of Traditional Chinese Medicine's journal, 2008 for Wang Shouchuan, Wang Lin for reference literature; 24(1): method 25 ~ 27), each sample is done serial dilution (2 with 2 multiple proportions
-1 ~-5), then be inoculated on the 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:
(old superfine, the oral liquid for clearing away lung-heat Contained Serum is to the experimentation of viral inhibition, Nanjing University of Traditional Chinese Medicine's journal, 2008 for Wang Shouchuan, Wang Lin for reference literature; 24(1): method 25 ~ 27), sample is inoculated on the 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 Aphanamixoid A
50Be respectively 2 at MDCK
-1.22
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 1% neutral red staining, survey the A value of 450 nm with microplate reader, after each was organized the A value and cuts virus control group A value, each experimental group A value was compared with cell control group A value and is obtained IC with above-mentioned brassboard
50, IC
50With TD
50Compare and obtain TI: suppress Flu A and at mdck cell CPE occurs, IC
50Be 2
-9.27, TI is 265.03.
Conclusion: Aphanamixoid A has very strong inhibitory action to influenza A virus, and safety, so Aphanamixoid A has widely application background in treatment influenza a virus infection disease.
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Citations (1)
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CN102266389A (en) * | 2011-08-30 | 2011-12-07 | 中国科学院长春应用化学研究所 | Application of cortex meliae in preparation of drug for inhibiting influenza A H1N1 virus |
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Publication number | Priority date | Publication date | Assignee | Title |
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CN102266389A (en) * | 2011-08-30 | 2011-12-07 | 中国科学院长春应用化学研究所 | Application of cortex meliae in preparation of drug for inhibiting influenza A H1N1 virus |
Non-Patent Citations (2)
Title |
---|
JIE-YUN CAIET AL.: "Aphanamixoid A, a Potent Defensive Limonoid, with a New Carbon Skeleton from Aphanamixis polystachya", 《ORGANIC LETTERS》, vol. 14, no. 10, 27 April 2012 (2012-04-27), pages 2524 - 2527 * |
高彦祥等: "吸附树脂在柑桔汁脱苦中的应用", 《饮料工业》, vol. 8, no. 3, 31 March 2005 (2005-03-31), pages 1 - 5 * |
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Application publication date: 20130327 |