CN103463002B - Application of racemosins A in preparation of medicine treating hemorrhagic fever with renal syndrome - Google Patents
Application of racemosins A in preparation of medicine treating hemorrhagic fever with renal syndrome Download PDFInfo
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- CN103463002B CN103463002B CN201310468818.1A CN201310468818A CN103463002B CN 103463002 B CN103463002 B CN 103463002B CN 201310468818 A CN201310468818 A CN 201310468818A CN 103463002 B CN103463002 B CN 103463002B
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- Prior art keywords
- racemosins
- hemorrhagic fever
- renal syndrome
- preparation
- medicine treating
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- 208000032982 Hemorrhagic Fever with Renal Syndrome Diseases 0.000 title claims abstract description 24
- 239000003814 drug Substances 0.000 title claims abstract description 24
- QZUNAFWZEXJWGD-UHFFFAOYSA-N racemosin Natural products C1=CC(=O)OC2=C1C(OC)=C1C=CC(C)(C)OC1=C2OC QZUNAFWZEXJWGD-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 11
- 241000700605 Viruses Species 0.000 abstract description 21
- 206010061192 Haemorrhagic fever Diseases 0.000 abstract description 4
- 230000002147 killing effect Effects 0.000 abstract description 4
- 231100000331 toxic Toxicity 0.000 abstract description 4
- 230000002588 toxic effect Effects 0.000 abstract description 4
- 238000002474 experimental method Methods 0.000 abstract description 3
- 208000011580 syndromic disease Diseases 0.000 abstract description 3
- 238000000338 in vitro Methods 0.000 abstract 1
- 238000001727 in vivo Methods 0.000 abstract 1
- 230000005764 inhibitory process Effects 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 11
- 208000015181 infectious disease Diseases 0.000 description 6
- 238000010166 immunofluorescence Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000003612 virological effect Effects 0.000 description 4
- 241001290352 Caulerpa racemosa Species 0.000 description 3
- 229930013930 alkaloid Natural products 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000002155 anti-virotic effect Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 206010062713 Haemorrhagic diathesis Diseases 0.000 description 1
- 241000150562 Hantaan orthohantavirus Species 0.000 description 1
- 208000021727 Hantavirus hemorrhagic fever with renal syndrome Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 206010030302 Oliguria Diseases 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000002364 anti-haemorrhagic effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 230000009351 contact transmission Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 208000031169 hemorrhagic disease Diseases 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 208000037920 primary disease Diseases 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses the new application of racemosins A in preparation of the medicine treating the hemorrhagic fever with the renal syndrome. Inhibition experiment research in vitro and in vivo shows that the racemosins A is low in toxic effect on cells, has direct killing effect on viruses of the hemorrhagic fever with renal syndrome and can inhibit reproduction of the viruses remarkably. Thus, the racemosins A is the effective and safe medicine treating the hemorrhagic fever with the renal syndrome.
Description
Technical field
The present invention relates to the novelty teabag of compound R acemosins A, particularly relate to the application of Racemosins 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 R acemosins A that the present invention relates to is one and delivers (Ding-Quan Liu in 2013, et al., Racemosins A and B, two novel bisindole alkaloids from the green alga Caulerpa racemosa.Fitoterapia, 91 (2013): 15 – 20.) noval chemical compound, this compound has brand-new framework types, and current purposes finds that it can weaken beta-amyloyd peptide
25-35(A β
25 – 35) human neuroblastoma cells SH-SY5Y cell injury (the Ding-Quan Liu that causes, et al., Racemosins A and B, two novel bisindole alkaloids from the green alga Caulerpa racemosa.Fitoterapia, 91 (2013): 15 – 20.), the purposes of the Racemosins 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 Racemosins 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 Racemosins A in preparation treatment hemorrhagic fever with renal syndrome medicine.
Described compound R acemosins A structure is as shown in formula I:
The purposes of the Racemosins 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 R acemosins A involved in the present invention is see document (Ding-Quan Liu, et al., Racemosins A and B, two novel bisindole alkaloids from the green alga Caulerpa racemosa.Fitoterapia, 91 (2013): 15 – 20.)
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 R acemosins A tablet involved in the present invention:
Get 5 g of compound Racemosins A and add 195 grams, dextrin, mixing, Conventional compression makes 1000.
Embodiment 2: the preparation of compound R acemosins A capsule involved in the present invention:
Get 5 g of compound Racemosins 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:Racemosins 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: Racemosins 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 Racemosins 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, use
Immunofluorescence checks.
(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 Racemosins A can not invade cell by blocking virus.
(3) the Racemosins 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 Racemosins 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 1Racemosins 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 2Racemosins A breeds hemorrhagic fever with renal syndrome virus
Compare with matched group, * p<0.05.
Sum up: the toxic action of Racemosins 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.Racemosins A in preparation treatment hemorrhagic fever with renal syndrome medicine, described compound R acemosins A structure is as shown in formula I:Formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310468818.1A CN103463002B (en) | 2013-10-10 | 2013-10-10 | Application of racemosins A in preparation of medicine treating hemorrhagic fever with renal syndrome |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310468818.1A CN103463002B (en) | 2013-10-10 | 2013-10-10 | Application of racemosins A in preparation of medicine treating hemorrhagic fever with renal syndrome |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103463002A CN103463002A (en) | 2013-12-25 |
| CN103463002B true CN103463002B (en) | 2015-06-17 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310468818.1A Expired - Fee Related CN103463002B (en) | 2013-10-10 | 2013-10-10 | Application of racemosins A in preparation of medicine treating hemorrhagic fever with renal syndrome |
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| Country | Link |
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| CN (1) | CN103463002B (en) |
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2013
- 2013-10-10 CN CN201310468818.1A patent/CN103463002B/en not_active Expired - Fee Related
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| CN103463002A (en) | 2013-12-25 |
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