CN103479629B - The application of Lycojaponicumin A in the medicine preparing anti respiratory syncytial virus - Google Patents
The application of Lycojaponicumin A in the medicine preparing anti respiratory syncytial virus Download PDFInfo
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- CN103479629B CN103479629B CN201310441788.5A CN201310441788A CN103479629B CN 103479629 B CN103479629 B CN 103479629B CN 201310441788 A CN201310441788 A CN 201310441788A CN 103479629 B CN103479629 B CN 103479629B
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- respiratory syncytial
- syncytial virus
- lycojaponicumin
- rsv
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Abstract
The invention discloses Lycojaponicumin A and prepare the application in anti respiratory syncytial virus medicine.The experiment proved that, Lycojaponicumin A has significant inhibitory action to respiratory syncytial virus RSV, the present invention is used for the treatment of respiratory syncytial virus rsv infection disease for Lycojaponicumin A is clinical provide experimental basis, certain directive significance is provided to the medicine of development anti respiratory syncytial virus RSV, there is important reference value.
Description
Technical field
The present invention relates to the application of Lycojaponicumin A in the medicine preparing anti respiratory syncytial virus (Respiratory Syncytial Virus, RSV).
Background technology
RSV mainly causes respiratory system infection, causes serious pneumonia infant, old age and immunodeficiency crowd, is one of important pathogen of infecting of human upper respiratory tract.
The compound L ycojaponicumin A that the present invention relates to is one and delivers (Wang in 2012, X.J.et al., 2012.Lycojaponicumins A-C, Three Alkaloids with an Unprecedented Skeleton from Lycopodium japonicum.Organic Letters 14 (10), New skeleton compound 2614-2617.), this compound has brand-new framework types, the purposes in preparation treatment respiratory syncytial virus (RSV) medicine that the present invention relates to is belonged to first public, because framework types belongs to brand-new framework types, and it is unexpectedly strong for respiratory syncytial virus (RSV) inhibit activities, there is not the possibility being provided any enlightenment by other compounds, possesses outstanding substantive distinguishing features, control simultaneously for respiratory syncytial virus (RSV) obviously has significant progress.
Summary of the invention
The invention provides the novelty teabag of Lycojaponicumin A in pharmacy:
The application of Lycojaponicumin A in the medicine of the anti-RSV of preparation.
Described compound L ycojaponicumin A structure is as shown in formula I:
The experiment proved that, Lycojaponicumin A has significant inhibitory action to RSV: suppress RSV to occur CPE effect (Cytopathic Effect, CPE) at HEK293 cell, IC
50be 2
-11.23, TI is 982.3.
The purposes of the Lycojaponicumin A that the present invention relates in preparation treatment respiratory syncytial virus (RSV) medicine belongs to first public, because framework types belongs to brand-new framework types, and it is unexpectedly strong for respiratory syncytial virus (RSV) inhibit activities, there is not the possibility being provided any enlightenment by other compounds, possess outstanding substantive distinguishing features, the control simultaneously for respiratory syncytial virus (RSV) obviously has significant progress.
Detailed description of the invention
The preparation method of compound L ycojaponicumin A involved in the present invention is see document (Wang, X.J.et al., 2012.Lycojaponicumins A-C, Three Alkaloids with an Unprecedented Skeleton from Lycopodium japonicum.Organic Letters 14 (10), 2614-2617.).
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not by any restriction of specific embodiment, but be limited by claim.
Embodiment 1: the preparation of compound L ycojaponicumin A tablet involved in the present invention:
Get 20 g of compound Lycojaponicumin A, add the customary adjuvant 180 grams preparing tablet, mixing, conventional tablet presses makes 1000.
Embodiment 2: the preparation of compound L ycojaponicumin A capsule involved in the present invention:
Get 20 g of compound Lycojaponicumin A, add prepare capsule customary adjuvant as starch 180 grams, mixing, encapsulatedly makes 1000.
Its pharmaceutically active is further illustrated below by pharmacodynamic experiment.
Experimental example: compound L ycojaponicumin A is to the Effect study of respiratory syncytial virus (RSV)
(1) configuration of compound L ycojaponicumin A: compound L ycojaponicumin A is dissolved in cell maintenance medium (containing the MEM of 2% new-born calf serum, GIBICO Products) for subsequent use.
(2) cell strain and Strain:
HEKC (HEK293, RSV virus sensitive cells) purchased from American Clontech company; Respiratory syncytial virus (RSV) Long strain is drawn from Chinese CDC virosis institute.
(3) cytotoxic assay:
Reference literature (Wang Shouchuan, Wang Lin, old superfine, oral liquid for clearing away lung-heat Contained Serum to the inhibiting experimentation of respiratory syncytial virus, Nanjing University of Traditional Chinese Medicine's journal, 2008; 24 (1): 25 ~ 27) method, does serial dilution (2 by sample with 2 multiple proportions
0 ~-5), then be inoculated on the HEK293 in 96 plate holes by dilution sequential lateral, every hole 100uL, every dilution factor longitudinally repeats 3 holes (A, B, C are capable), parallel 1 ~ 6 hole of microwell plate D of setting is as cell controls, 7 ~ 12 holes not inoculating cell are blank, microscope observes CPE lower every day, Continuous Observation 7d, neutral red staining, measure OD value at 540nm wavelength, by experimental group calculating cell survival rate compared with cell controls group OD value, calculate medicine half cytotoxic concentration (TD by Reed-Muench method
50).
(4) toxin inhibitory test:
Reference literature (Wang Shouchuan, Wang Lin, old superfine, oral liquid for clearing away lung-heat Contained Serum to the inhibiting experimentation of respiratory syncytial virus, Nanjing University of Traditional Chinese Medicine's journal, 2008; 24 (1): 25 ~ 27) method, by sample by dilution order (2
-2 ~-13) be laterally inoculated in 96 plate holes cell monolayer on, every hole 100uL, every dilution factor longitudinally repeats 4 holes, and A, B, C of microwell plate are capable to be added containing 100 TCID
50viral 100uL as test group, capable the supplementing of D waits capacity cell maintenance medium to be variable concentrations drug control, and the parallel F that establishes is capable of virus control, E capable 1 ~ 12 as cell controls.37 DEG C, 5%CO
2cultivate, every day observes CPE, Continuous Observation 4d.When there is more than 90% CPE in virus control, add 1% neutral red staining, A value is read at wavelength 540nm wavelength by microplate reader, each group of A value removes virus control group A value, by each test group compared with cell controls group A value, obtain cell survival rate, calculate half by Reed-Muench method and press down malicious concentration (IC
50), TD the most at last
50and IC
50compare to obtain and press down malicious index (TI).
(5) result:
1. sample TD
50mensuration: cellular control unit basis of microscopic observation adherent growth is fine and close, form is good.Compound L ycojaponicumin A is to the TD of HEK293
50be 2
-1.29.
2. poison experiment is pressed down: the adherent densification of cellular control unit, form are good.Microscopic observation finds, RSV virus control group occurs the CPE of more than 90% at 2d, and RSV strengthens with refractivity at HEK293CPE, change is justified, comes off, is broken for principal character.
And toxin inhibitory test respectively organizes cell, according to diluted sample gradient, there is CPE in gradient rule:
RSV-HEK293 test group cell is before the 9th dilution factor, and cell is completely protected, occurs CPE afterwards, and CPE reduces with sample concentration and increases the weight of gradually.
By above-mentioned brassboard 1% neutral red staining, survey 450nmA value by microplate reader, after each group A value cuts virus control group A value, each experimental group A value obtains IC compared with cell controls group A value
50, IC
50with TD
50compare and obtain TI: suppress RSV, at HEK293 cell, CPE, IC occur
50be 2
-11.23, TI is 982.3.
Conclusion: Lycojaponicumin A has the effect that significant anti-pair glues coe virus respiratory syncytial virus RSV, can be used for preparing anti-pair and glue coe virus respiratory syncytial virus RSV medicine.
Claims (1)
- The application of 1.Lycojaponicumin A in the medicine preparing anti respiratory syncytial virus, described compound L ycojaponicumin A structure as formula Ishown in:formula I.
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| CN201310441788.5A CN103479629B (en) | 2013-09-23 | 2013-09-23 | The application of Lycojaponicumin A in the medicine preparing anti respiratory syncytial virus |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103059043A (en) * | 2011-10-24 | 2013-04-24 | 中国医学科学院药物研究所 | Clavatine A-C and preparation method as well as pharmaceutical composition and application thereof |
-
2013
- 2013-09-23 CN CN201310441788.5A patent/CN103479629B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103059043A (en) * | 2011-10-24 | 2013-04-24 | 中国医学科学院药物研究所 | Clavatine A-C and preparation method as well as pharmaceutical composition and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| Lycojaponicumins A-C,Three Alkaloids with an Unprecedented Skeleton from Lycopodium japonicum;Xiao-Jing Wang, et al;《Organic Letters》;20121231;第14卷(第10期);2614-2617 * |
| 呼吸道合胞病毒感染巨噬细胞诱导炎性基因表达的部分机制研究;黄升海等;《中国人兽共患病学报》;20091231;第25卷(第10期);948-952 * |
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Address after: Tiefu iron rich street Pizhou city 221331 Jiangsu city of Xuzhou Province Patentee after: Nanjing Guangkangxie Biomedical Technology Co., Ltd. Address before: Metro Technology Building No. 69 Olympic Avenue in Jianye District of Nanjing city in Jiangsu province 210019 01 5 storey buildings Patentee before: Nanjing Guangkangxie Biomedical Technology Co., Ltd. |
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Inventor after: Duan Chunmei Inventor before: Jiang Chunping Inventor before: Wang Hui |
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Effective date of registration: 20171221 Address after: The 404600 Chongqing city Fengjie County Zhenping on Village 7 Patentee after: FENGJIE DONGYANG BUILDING MATERIALS CO., LTD. Address before: Tiefu iron rich street Pizhou city 221331 Jiangsu city of Xuzhou Province Patentee before: Nanjing Guangkangxie Biomedical Technology Co., Ltd. |