CN102861031B - Application of Gypensapogenin B in medicine for resisting respiratory syncytial virus - Google Patents
Application of Gypensapogenin B in medicine for resisting respiratory syncytial virus Download PDFInfo
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- CN102861031B CN102861031B CN201210417920.4A CN201210417920A CN102861031B CN 102861031 B CN102861031 B CN 102861031B CN 201210417920 A CN201210417920 A CN 201210417920A CN 102861031 B CN102861031 B CN 102861031B
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- gypensapogenin
- respiratory syncytial
- rsv
- medicine
- syncytial virus
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- NNUMQZNZQGQGCN-AGHUFMIKSA-N gypensapogenin b Chemical compound O=C1C(=C(C)C)CC([C@@H]2[C@@H]3[C@@]([C@@]4(CCC5=C([C@H]6CC[C@H](O6)C5(C)C)[C@H]4CC3)C)(C)CC2)=C1 NNUMQZNZQGQGCN-AGHUFMIKSA-N 0.000 title claims abstract description 44
- 241000725643 Respiratory syncytial virus Species 0.000 title claims abstract description 40
- 239000003814 drug Substances 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims description 10
- 230000003097 anti-respiratory effect Effects 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 abstract description 6
- 238000002474 experimental method Methods 0.000 abstract description 5
- 208000035473 Communicable disease Diseases 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 17
- 150000001875 compounds Chemical class 0.000 description 14
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 241000700605 Viruses Species 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 240000006509 Gynostemma pentaphyllum Species 0.000 description 3
- 235000002956 Gynostemma pentaphyllum Nutrition 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- PGSADBUBUOPOJS-UHFFFAOYSA-N neutral red Chemical compound Cl.C1=C(C)C(N)=CC2=NC3=CC(N(C)C)=CC=C3N=C21 PGSADBUBUOPOJS-UHFFFAOYSA-N 0.000 description 3
- 229930182490 saponin Natural products 0.000 description 3
- 150000007949 saponins Chemical class 0.000 description 3
- 235000017709 saponins Nutrition 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 150000003648 triterpenes Chemical class 0.000 description 3
- 231100000645 Reed–Muench method Toxicity 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- INLFWQCRAJUDCR-IQVMEADQSA-N (1R,2S,4S,5'S,6R,7S,8R,9S,12S,13S)-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icosane-6,2'-oxane] Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CCCCC4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@H](C)CO1 INLFWQCRAJUDCR-IQVMEADQSA-N 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 235000003143 Panax notoginseng Nutrition 0.000 description 1
- 241000180649 Panax notoginseng Species 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 230000000120 cytopathologic effect Effects 0.000 description 1
- OORMXZNMRWBSTK-UHFFFAOYSA-N dammaran Natural products C1CCC(C)(C)C2CCC3(C)C4(C)CCC(C(C)CCCC(C)C)C4CCC3C21C OORMXZNMRWBSTK-UHFFFAOYSA-N 0.000 description 1
- 238000000280 densification Methods 0.000 description 1
- 239000012470 diluted sample Substances 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Steroid Compounds (AREA)
Abstract
The invention relates to application of Gypensapogenin B in preparing a medicine for resisting respiratory syncytial viruses. The experiments prove that Gypensapogenin B has outstanding inhibiting effect on respiratory syncytial viruses (RSV). The invention provides experiment basis for that Gypensapogenin B is used for clinically treating infectious diseases of respiratory syncytial viruses (RSV), and provides a certain guiding meaning for preparing the medicine for resisting respiratory syncytial viruses (RSV), as well as has an important reference value.
Description
Technical field
The present invention relates to the application of Gypensapogenin B in the medicine of preparation 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 human upper respiratory tract infection.
The chemical compound Gypensapogenin B that the present invention relates to is one and delivered (Li in 2012, N. et al., 2012. Triterpenes possessing an unprecedented skeleton isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum. European Journal of Medicinal Chemistry 50,173 – 178.) New skeleton compound, this chemical compound has brand-new framework types, present purposes only relates to the cytotoxic activity (Li of human tumor cell line, N. et al., 2012. Triterpenes possessing an unprecedented skeleton isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum. European Journal of Medicinal Chemistry 50,173 – 178.), belong to open first for the purposes in preparation treatment respiratory syncytial virus (RSV) medicine that the present invention relates to, because framework types belongs to brand-new framework types, and it suppresses active unexpectedly strong for respiratory syncytial virus (RSV), 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 respiratory syncytial virus (RSV) obviously has significant progress.
Summary of the invention
The invention provides the new purposes of Gypensapogenin B in pharmacy:
The application of Gypensapogenin B in the medicine of the anti-RSV of preparation.
Described chemical compound Gypensapogenin B structure is shown in formula I:
Formula I
The experiment proved that, Gypensapogenin B has significant inhibitory action to RSV: suppress RSV and CPE effect (Cytopathic Effect, CPE), IC occur at the HEK293 cell
50Be 2
-10.50, TI is 274.38.
The purposes of the Gypensapogenin B that the present invention relates in preparation treatment respiratory syncytial virus (RSV) medicine belongs to open first, because framework types belongs to brand-new framework types, and it suppresses active unexpectedly strong for respiratory syncytial virus (RSV), 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 respiratory syncytial virus (RSV) obviously has significant progress.
The specific embodiment
The preparation method of chemical compound Gypensapogenin B involved in the present invention is referring to document (Li, N. et al., 2012. Triterpenes possessing an unprecedented skeleton isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum. European Journal of Medicinal Chemistry 50,173 – 178. and Wei, J.X. et al., 1982. Two new dammaran sapogenins from leaves of Panax notoginseng. Planta Medica, 45 (3): 167-171.).
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 chemical compound Gypensapogenin B tablet involved in the present invention:
Get 20 and digest compound Gypensapogenin B, add conventional adjuvant 180 grams of preparation tablet, mixing, conventional tablet machine are made 1000.
Embodiment 2: the preparation of chemical compound Gypensapogenin B capsule involved in the present invention:
Get 20 and digest compound Gypensapogenin B, 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: chemical compound Gypensapogenin B is to the effect research of respiratory syncytial virus (RSV)
(1) configuration of chemical compound Gypensapogenin B: be dissolved in the cell maintenance medium (MEM that contains 2% new-born calf serum, GIBICO company product) chemical compound Gypensapogenin B for subsequent use.
(2) cell strain and Strain:
HEKC (HEK293, RSV virus sensitive cells) is available from U.S. Clontech company; Respiratory syncytial virus (RSV) Long strain is drawn from Chinese CDC virosis institute.
(3) cytotoxic assay:
(old superfine, the oral liquid for clearing away lung-heat Contained Serum is to the inhibiting experimentation of respiratory syncytial virus, Nanjing University of Traditional Chinese Medicine's journal, 2008 for Wang Shouchuan, Wang Lin for reference literature; 24(1): method 25 ~ 27), sample is done serial dilution (2 with 2 multiple proportions
0 ~-5), then be inoculated on the HEK293 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).
(4) toxin inhibitory test:
(old superfine, the oral liquid for clearing away lung-heat Contained Serum is to the inhibiting experimentation of respiratory syncytial virus, Nanjing University of Traditional Chinese Medicine's journal, 2008 for Wang Shouchuan, Wang Lin for reference literature; 24(1): method 25 ~ 27), sample is pressed dilution order (2
-2 ~-13) laterally be inoculated on the cell monolayer in 96 plate holes, 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).
(5) result:
1. sample TD
50Mensuration: the cellular control unit microscopically observes that adherent growth is fine and close, form is good.Chemical compound Gypensapogenin B is to the TD of HEK293
50Be 2
-2.53
2. press down the poison experiment: the adherent densification of cellular control unit, form are good.Microscopic observation discovery, RSV virus control group are at the CPE of 2d appearance more than 90%, and RSV strengthens, becomes and justify, come off, be broken for principal character with refractivity at HEK293 CPE.
And toxin inhibitory test is respectively organized cell, and according to the diluted sample gradient, CPE appears in the gradient rule:
RSV-HEK293 test group cell is before the 9th dilution factor, and cell is fully protected, CPE occurs afterwards, and CPE reduces with sample concentration and increases the weight of gradually.
With 1% neutral red staining, survey 450nmA value 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 with above-mentioned brassboard
50, IC
50With TD
50Compare and obtain TI: suppress RSV and at the HEK293 cell CPE, IC occur
50Be 2
-10.50, TI is 274.38.
Conclusion: Gypensapogenin B has the effect of the sticking coe virus respiratory syncytial virus RSV of significant anti-pair, can be used for preparing the sticking coe virus respiratory syncytial virus RSV medicine of anti-pair.
Claims (1)
1.Gypensapogenin B the preparation anti respiratory syncytial virus medicine in application, described chemical compound Gypensapogenin B structure as
Formula IShown in:
Formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210417920.4A CN102861031B (en) | 2012-10-26 | 2012-10-26 | Application of Gypensapogenin B in medicine for resisting respiratory syncytial virus |
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|---|---|---|---|
| CN201210417920.4A CN102861031B (en) | 2012-10-26 | 2012-10-26 | Application of Gypensapogenin B in medicine for resisting respiratory syncytial virus |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102861031A CN102861031A (en) | 2013-01-09 |
| CN102861031B true CN102861031B (en) | 2013-10-23 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210417920.4A Active CN102861031B (en) | 2012-10-26 | 2012-10-26 | Application of Gypensapogenin B in medicine for resisting respiratory syncytial virus |
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| Country | Link |
|---|---|
| CN (1) | CN102861031B (en) |
-
2012
- 2012-10-26 CN CN201210417920.4A patent/CN102861031B/en active Active
Non-Patent Citations (2)
| Title |
|---|
| Ning Li等.Triterpenes possessing an unprecedented skeleton isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum.《European Journal of Medicinal Chemistry》.2012,第50卷173-178. |
| Triterpenes possessing an unprecedented skeleton isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum;Ning Li等;《European Journal of Medicinal Chemistry》;20120203;第50卷;173-178 * |
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| CN102861031A (en) | 2013-01-09 |
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Effective date of registration: 20211221 Address after: Fengli town Xinjian West Road, Rudong County, Nantong City, Jiangsu Province 226400 Patentee after: Rudong Wenyuan investment and Development Co., Ltd Address before: 226400 No.10 Fandi South Road, juegang Town, Rudong County, Nantong City, Jiangsu Province Patentee before: Rudong industrial and commercial information consulting service center |
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