CN103520171B - Application of kadcoccitones A in preparing medicament for treating hemorrhagic fever with renal syndrome - Google Patents
Application of kadcoccitones A in preparing medicament for treating hemorrhagic fever with renal syndrome Download PDFInfo
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- CN103520171B CN103520171B CN201310496784.7A CN201310496784A CN103520171B CN 103520171 B CN103520171 B CN 103520171B CN 201310496784 A CN201310496784 A CN 201310496784A CN 103520171 B CN103520171 B CN 103520171B
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- kadcoccitones
- hemorrhagic fever
- renal syndrome
- virus
- treating hemorrhagic
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Abstract
The invention relates to a novel application of kadcoccitones A in preparing a medicament for treating hemorrhagic fever with renal syndrome. In vitro and in vivo inhibition experiment researches show that the kadcoccitones A has low toxic effects on cells, direct killing effects on hemorrhagic fever with renal syndrome viruses, can obviously inhibit virus proliferation, has obvious protective effects on shrew-mice infected with the viruses and ensures that the onset time is delayed, the disease course is prolonged and the death rate is reduced. Therefore, the kadcoccitones A is a safe and effective medicament for treating hemorrhagic fever with renal syndrome.
Description
Technical field
The present invention relates to the novelty teabag of compound K adcoccitones A, particularly relate to the application of Kadcoccitones A in preparation treatment hemorrhagic fever with renal syndrome medicine.
Background technology
Hemorrhagic fever with renal syndrome is caused by haemorrhagic fever with renal syndrome virus (or claiming Hantaan virus), take muroid as the disease of natural focus of major source of infection; By respiratory tract, digestive tract, contact transmission, mother-to-baby transmission and arthropod-borne; With the acute viral infectious disease that heating, bleeding tendency and kidney damage are main clinical characteristics, typical hemorrhagic fever generally has heating, hypotension, oliguria, polyuria and recovers five phase processes, as very high in dealt with case fatality rate improperly; Propagation almost each continent all over the world of HFRS virus.China have semicentennial popular time, since the eighties mid-term, China's primary disease year morbidity number exceedes 100,000, has become except viral hepatitis, has endangered maximum a kind of viral disease.
The compound K adcoccitones A that the present invention relates to is one and delivers (Cheng-Qin Liang in 2012, et al., Kadcoccitones A and B, Two New6/6/5/5-Fused Tetracyclic Triterpenoids from Kadsura coccinea.Organic Letters, 2012, 14 (24): 6362 – 6365.) noval chemical compound, this compound has brand-new framework types, current purposes only relates to inhibiting HIV, invalid to kinds of tumors, (Cheng-Qin Liang, et al., Kadcoccitones A and B, Two New6/6/5/5-Fused Tetracyclic Triterpenoids from Kadsura coccinea.Organic Letters, 2012, 14 (24): 6362 – 6365.), the purposes of the Kadcoccitones A that the present invention relates in preparation treatment hemorrhagic fever with renal syndrome medicine belongs to first public.
Summary of the invention
The object of the invention is in studying according to existing Kadcoccitones A, not find that it has the present situation of the report for the treatment of hemorrhagic fever with renal syndrome activity, provide the application of Kadcoccitones A in preparation treatment hemorrhagic fever with renal syndrome medicine.
Described compound K adcoccitones A structure is as shown in formula I:
The purposes of the Kadcoccitones A that the present invention relates in preparation treatment hemorrhagic fever with renal syndrome medicine belongs to first public, because framework types belongs to brand-new framework types, and it is active strong for treatment hemorrhagic fever with renal syndrome, possess outstanding substantive distinguishing features, be used for the treatment of hemorrhagic fever with renal syndrome simultaneously and obviously there is significant progress.
Detailed description of the invention
The preparation method of compound K adcoccitones A involved in the present invention is see document (Cheng-Qin Liang, et al., Kadcoccitones A and B, Two New6/6/5/5-Fused Tetracyclic Triterpenoids from Kadsura coccinea.Organic Letters, 2012,14 (24): 6362 – 6365.)
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 K adcoccitones A tablet involved in the present invention:
Get 5 g of compound Kadcoccitones A and add 195 grams, dextrin, mixing, Conventional compression makes 1000.
Embodiment 2: the preparation of compound K adcoccitones A capsule involved in the present invention:
Get 5 g of compound Kadcoccitones A and add starch 195 grams, mixing, encapsulatedly makes 1000.
Its pharmaceutically active is further illustrated below by pharmacodynamic experiment.
The experimentation of the anti-hemorrhagic fever with renal syndrome virus of experimental example 1:Kadcoccitones A
(1) to hemorrhagic fever with renal syndrome virus body outer suppressioning experiment
1 material
(1) Strain: international standard hemorrhagic fever with renal syndrome virus 76-118 strain, is preserved by China Preventive Medicial Science Institute's institute.Test the virus (100TCID50/ml) containing 100 virus infection titers with every milliliter.
(2) cell: the E6 clone system that African green monkey kidney Vero goes down to posterity, 139 ~ 141 generations.Wherein containing 3% calf serum maintenance medium.
(3) medicine: Kadcoccitones A, each dilution factor is all prepared by maintenance medium.Blank is set up in experimentation.
2 methods
(1) medicine is to the toxic action of Vero E6 cell.By the Vero E6 cell growing up to monolayer respectively with Kadcoccitones A 0.05,0.1,0.5,1.0,2.0,3.0,5.0,7.5, after the drug level process of 10.0ug/ml cultivates 2 weeks, observation of cell form.
(2) medicine invades the blocking effect of cell to hemorrhagic fever with renal syndrome virus.With 0.2,0.5,1.0,2.0,3.0, the drug level pretreatment cell of 5.0ug/ml after 12 hours, then attacks with hemorrhagic fever with renal syndrome virus, check by immunofluorescence after cultivating 2 weeks.
(3) to the direct killing action of hemorrhagic fever with renal syndrome virus.With 0.5,1.0,2.0,3.0,5.0, the drug level of 7.5ug/ml and the viral mixed in equal amounts of 100TCID50/0.1ml, after effect different time, then by its infection cell, check by immunofluorescence.
(4) to the inhibited proliferation of hemorrhagic fever with renal syndrome virus.Virus infected cell, after 24 hours, adds cell culture medium with different drug level, checks after cultivating 2 weeks by immunofluorescence.
3 observation index
With immuno-fluorescence assay Intracellular viral antigens, if infection cell has no fluorescent positive, represent that virus has been killed or has suppressed, calculate antiviral index simultaneously.
4 results
(1) after the drug level group of 10.0ug/ml cultivates 5 days, cell granulations increases, and refractivity is poor, and cellular morphology obviously changes, part cell detachment, and all the other each concentration have no the toxic action of medicine to Vero E6 cell.
(2) all there is specificity fluorescent at different time pretreated experimental group cell and the cellular control unit of non-medication process in each concentration, and virus infection titer is 105/0.1ml, antiviral index 1.Show that Kadcoccitones A can not invade cell by blocking virus.
(3) the Kadcoccitones A of 3.0ug/ml drug level has direct kill activity to virus, more than this concentration each group, its infection titer and matched group are than all there were significant differences (P<0.05), and drug level increases, and antivirus action strengthens (see table 1).
(4) the Kadcoccitones A of 0.5ug/ml drug level has inhibitory action to virus multiplication, more than this concentration each group, its infection titer and matched group are than all there were significant differences (P<0.05), and drug level increases, and antivirus action strengthens (see table 2).
Table 1Kadcoccitones A is to the direct killing action (X ± s) of hemorrhagic fever with renal syndrome virus
Compare with matched group, * p<0.05.
The inhibitory action (X ± s) that table 2Kadcoccitones A breeds hemorrhagic fever with renal syndrome virus
Compare with matched group, * p<0.05.
Sum up: the toxic action of Kadcoccitones A to cell is low; Direct killing action is had to hemorrhagic fever with renal syndrome virus; Have obvious inhibitory action to the propagation of hemorrhagic fever with renal syndrome virus, drug level increases, and antiviral efficacy increases.
Claims (1)
- The application of 1.Kadcoccitones A in preparation treatment hemorrhagic fever with renal syndrome medicine, described compound K adcoccitones A structure is as shown in formula I:Formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310496784.7A CN103520171B (en) | 2013-10-21 | 2013-10-21 | Application of kadcoccitones A in preparing medicament for treating hemorrhagic fever with renal syndrome |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201310496784.7A CN103520171B (en) | 2013-10-21 | 2013-10-21 | Application of kadcoccitones A in preparing medicament for treating hemorrhagic fever with renal syndrome |
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| Publication Number | Publication Date |
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| CN103520171A CN103520171A (en) | 2014-01-22 |
| CN103520171B true CN103520171B (en) | 2015-01-07 |
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| CN201310496784.7A Expired - Fee Related CN103520171B (en) | 2013-10-21 | 2013-10-21 | Application of kadcoccitones A in preparing medicament for treating hemorrhagic fever with renal syndrome |
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2013
- 2013-10-21 CN CN201310496784.7A patent/CN103520171B/en not_active Expired - Fee Related
Non-Patent Citations (2)
| Title |
|---|
| Kadcoccitones A and B, Two New 6/6/5/5-Fused Tetracyclic Triterpenoids from Kadsura coccinea;Cheng-Qin Liang et al;《ORGANIC LETTER》;20121231;第14卷(第24期);6362-6365 * |
| 五味子属植物降三萜成分研究进展;王薇丹等;《中成药》;20091231;第31卷(第12期);1912-1916 * |
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