CN106166151A - Indolal application in the medicine of resisiting influenza virus and the diseases associated with inflammation of preparation treatment influenza virus mediation - Google Patents
Indolal application in the medicine of resisiting influenza virus and the diseases associated with inflammation of preparation treatment influenza virus mediation Download PDFInfo
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- CN106166151A CN106166151A CN201610675142.7A CN201610675142A CN106166151A CN 106166151 A CN106166151 A CN 106166151A CN 201610675142 A CN201610675142 A CN 201610675142A CN 106166151 A CN106166151 A CN 106166151A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
- A61K36/315—Isatis, e.g. Dyer's woad
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Abstract
The present invention provides indolal application in the medicine of diseases associated with inflammation that resisiting influenza virus and treatment are mediated by influenza virus, provides a kind of new way for clinical treatment influenza virus property disease.Described indolal has the effect that the inflammatory factor that progeny virus replicates and suppression influenza virus mediates of suppression influenza virus produces.The feature that indolal of the present invention has safely and effectively in terms for the treatment of influenza virus property disease, toxic and side effects is little.
Description
Technical field
The invention belongs to biomedicine technical field, particularly relate to a kind of Radix Isatidis indolal in resisiting influenza virus and system
Application in the medicine of the diseases associated with inflammation of standby influenza virus mediation.
Background technology
Influenza is a kind of Acute respiratory infectious disease caused by influenza infection, has rapid onset, infectiousness strong etc.
Feature, the most repeatedly causes worldwide being very popular, serious harm human and animal's life and health.The influenza infection initial stage,
Virus induction natural immune system generation a large amount of proinflammatory reaction cytokines participation immune response, but the inflammatory factor of excess
May result in the inflammation chain reactions such as a large amount of apoptosis, capillary permeability raising, leukocyte infiltration, pulmonary edema and airway obstruction
(i.e. " cytokine storm "), cytokine storm can increase the weight of lung injury, and acute respiratory distress can be caused time serious comprehensive
Disease (ARDS).
Many results of study show, highly pathogenic influenza infection causes the reason of death to be more because virus sense
The pathology damage that the immunoreation that dye induces host excessive causes, rather than the direct cell injury caused by virus replication.Therefore, exist
During virus Infective, if the inflammatory and immune response of host can be regulated in time, reduce immunity to greatest extent and excessively cause
Lung damage, then can significantly slow virus and infect the symptom that causes, reduce the death of human or animal.Approval is used for the most clinically
Anti-influenza virus medicament two class medicine (M2 inhibitors of ion channels and neuraminidase inhibitor) all important with influenza virus
Albumen is action target spot, to host without regulation effect, and the most directly effect of the inflammation of suppression influenza virus induction.And face
On bed, Chinese medicine has the action character of multicomponent, too many levels, not only has direct antivirus action, moreover it is possible to regulation virus causes
The complex process of immunopathogenesis damage, has the advantage of uniqueness in the treatment of influenza.Indolal is the principal monomer of Radix Isatidis
One of composition, previously clinical experience and lot of experiments prove that Radix Isatidis has good result in treatment of influenza, and, plate
The effective ingredient of Lan Genzhong has the function of regulation host immune.
Therefore, from Radix Isatidis, separate preparation filter out effective suppression influenza virus and the inflammation of resisiting influenza virus mediation
The effective ingredient of disease reaction, probes into the mechanism of action of its uniqueness, sends out for anti-influenza virus medicament research and development and China's Chinese medicine
Exhibition is significant.
The structural formula separating and purifying the indolal obtained at present from Radix Isatidis is:
About indolal in suppression influenza virus and the aborning application of the inflammatory factor of suppression influenza virus mediation
Have no report.
Summary of the invention
It is an object of the invention to provide the new opplication of indolal, i.e. indolal at resisiting influenza virus or to prepare by influenza
The virus-mediated application in diseases associated with inflammation medicine, provides new approach for the influenza disease of clinical treatment.
Further, the propagation of described indolal infected by influenza is inhibited, the most such as suppresses human influenza virus
H1N1 (PR8 type strain), also has the effect that the inflammatory factor of suppression influenza virus mediation produces, concrete as susceptible in suppression artificial abortion
Poison H1N1 (PR8 type strain) infects the expression of human airway epithelial cells (16HBE) inflammatory factor afterwards, and the present invention also further provides for
Indolal application in preparing above-mentioned drugs with function.Inflammatory factor includes but not limited to IL-6, IP-10, RENTES.
Described influenza virus is including, but not limited to first, Influenza B virus and bird flu virus；Described first, influenza B
Virus and bird flu virus are including, but not limited to human influenza H1N1 hypotype (PR8 type strain), novel H1N1 hypotype, H3N2
Hypotype and IFN Type B, and Avian Influenza Virus H9N2.
Further, described indolal can be to extract from natural plants Radix Isatidis.
Further, described medicine can be made into any dosage form pharmaceutically allowed, its dosage form for example, tablet, capsule etc..
The present invention also provides for a kind of for treating influenza or the medicine of inflammation mediated by influenza virus, described medicine its live
Property composition includes previously described indolal.
The medicine that the present invention is a kind of safely and effectively for the offer of clinical treatment influenza virus property disease, toxic and side effects is little.
The present invention uses plaque to reduce test method(s) and verifies that the indolal convection current extracting from Radix Isatidis is susceptible in the therapeutic mode
The inhibitory action that poison replicates, with oseltamivir phosphate as positive control drug.Observe indolal to the toxicity of mdck cell and right
The inhibitory action that influenza virus is replicated, utilizes mtt assay to record the half poisonous concentration (TC of the indolal extracting from Radix Isatidis50) it is
335.57μg/mL.Plaque reduces result of the test display indolal and significantly inhibits influenza A in the range of 25-100 μ g/mL
H1N1 breeds.
The effect of the inflammatory factor generation that the present invention acts on host cell suppression influenza virus mediation to indolal is carried out
Inquire into, use the technique study Drug inhibition influenza virus of ELISA to stimulate human airway epithelial cells (16HBE) inflammatory factor afterwards
Expression.Result display indolal significantly reduces influenza virus H1N1 (PR8) at 100 μ g/mL stimulates 16HBE cell 24 little
Inflammatory factor level time after.Indolal both can suppress influenza virus answering in mdck cell when concentration is 100 μ g/mL
System, it is also possible to the expression of the inflammatory factor of suppression influenza virus mediation；When concentration is 50 μ g/mL and 25 μ g/mL to inflammation because of
The expression of son does not has inhibitory action, but can effectively suppress the duplication of influenza virus.
Accompanying drawing explanation
Fig. 1 is shown that the indolal inhibitory action replicating H1N1 (PR8) influenza virus on mdck cell；
Fig. 2 A-2D be shown that medicine to human airway epithelial cells (16HBE) drug toxicity and medicine effect 24 hours after
The protein expression of the inflammatory factor of suppression influenza virus mediation.
Detailed description of the invention
For being best understood from the present invention, below in conjunction with specific embodiment, present invention is described further, but the present invention
Protection content be not limited to following instance.
Embodiment 1 indolal monomer component is isolated and purified, Structural Identification
Indolal separation process:
Ethyl acetate portion 30g, mixes sample with silica gel (200-300 mesh), carry out after volatilizing silica gel column chromatography (200-300 mesh,
10 × 20cm), make eluent gradient eluting (1:1-0:1, v/v) with petroleum ether-ethyl acetate, finally use methanol-eluted fractions.Often
500ml connects a component, each eluent decompression and solvent recovery respectively, detects with TLC, merges the eluent that composition is similar, altogether
Obtain 8 parts Fr.A-Fr.H.
Each component is again with analytical HPLC combining data detection Fr.B～Fr.D.Fr.B～Fr.D sepia paste, about 7.8g,
Mix sample with silica gel (200-300 mesh), carry out silica gel column chromatography (200-300 mesh) after volatilizing, flow with petroleum ether-ethyl acetate
Phase gradient eluting (10:1-8:1-3:1-3:2-0:1, v/v).Every 100ml connects a component, and each eluent recovered under reduced pressure respectively is molten
Agent, detects with TLC, merges the eluent that composition is similar, obtains 7 components, Fr.1～Fr.7.
Fr.3 methanol dissolves mixes silica gel (200～300 mesh), upper silicagel column (200～300 mesh) after volatilizing, with petroleum ether-
Ethyl acetate does eluent gradient eluting (3:1-3:2-3:2, v/v), finally rushes post, petroleum ether-ethyl acetate (3:1) with methanol
Elution fraction preparative high-pressure liquid phase separates, and does eluent gradient eluting with methanol-water, obtains 28 components, with analytical type
High-pressure liquid phase checks, obtains pale yellow crystals from 15～17 components, obtain after recrystallizing methanol compound B-11 4 (3-indolal,
4.3mg)
Indolal structure determination:
Pale yellow crystals (methanol), mp113～115 DEG C.Nucleus magnetic hydrogen spectrum shows 6 proton signals, is in low field.1(2H m) is phenyl ring AA ' BB ' coupling system for H-NMR δ: 8.18 (1H, d, J=1.6Hz), 7.50 (1H, d, J=1.6Hz), 7.30
The proton signal of system.δ 9.90 (1H, s) is the sharp-pointed unimodal aldehyde radical proton signal chemical shift numerical value that meets, and δ 8.12 (1H, s)
Proton signal on corresponding indole ring.It is accredited as 3-indolal according to list of references [1].([1] is left beautiful, Li Jianbei, Xu Jing etc.
The chemical constitution study of Radix Isatidis. CHINA JOURNAL OF CHINESE MATERIA MEDICA, 2007,32 (8): 688-691.)
New effect that indolal is had by the test example provided below is confirmed, is used for being further elucidated with the present invention,
And be not meant to limit the scope of the invention.
Test example 1 indolal In Vitro Anti influenza activity
1.1. material
1.1.1 drug-positive comparison medicine: oseltamivir phosphate: purchased from GIBCO company of the U.S., article No. Y0001337；Experiment
Medicine--indolal: Radix Isatidis raw medicinal herbs is provided by Guangzhou Baiyunshan Heji Huangpu Chinese Medicine Co., Ltd., picks up from Heilungkiang grand celebration
And isatis root GAP base, Fuyang, Chinese Academy of Sciences south China plant Yuan Yehua state researcher it is accredited as Isatis indigotica Fort. Isatis
The root of infigotica Fort., i.e. Radix Isatidis.Carry out extracting according to embodiment 1 by it, purification, qualification, it is thus achieved that indolal carries
Take thing.
1.1.2 cell Madin-Darby canine kidney(cell line) (MDCK) (MDCK) is quoted from American Type Culture Collection committee of Chinese Academy of Sciences cell bank；This bacterium
Plant and be saved in China typical culture collection center, deposit number: CCTCC NO:C201561；Taxonomy is named: Madin-Darby canine kidney(cell line) (MDCK)
(MDCK NS1)；Preservation address: Wuhan University of Wuhan, China city；Postcode: 430072, preservation date: 2015 05 month 21
Day.
People's laryngeal cancer cell is quoted from American Type Culture Collection committee of Chinese Academy of Sciences cell bank；This fungi preservation is trained at Chinese Typical Representative
Support thing preservation center, deposit number: CCTCC NO:C201562；Taxonomy is named: people's laryngeal cancer cell (Hep-2NS2)；Preservation ground
Location: Wuhan University of Wuhan, China city；Postcode: 430072, preservation date: on 05 21st, 2015.
1.1.3 strains of influenza viruses influenza A H1N1 influenza virus PR8 strain (A/PR/8/34, H1N1), A type H3N2 influenza virus
Aichi strain (A/Aichi/2/68, H3N2) is purchased from American classic culture collecting center (ATCC)；New influenza A H1N1 is sick
Strain (A/Guangzhou/GIRD07/09, H1N1, Genebank No.HM014332.1), Influenza B virus (B/
Guangzhou/GIRD08/09) it is this room clinical separation strain, influenza A virus H7N3 (A/Duck/Guangdong/1994,
H7N3), H9N2 (A/Chicken/Guangdong/1996, H9N2) is taught favour by College of Veterinary Medicine, South China Agricultural University Chen Jianxin
Give.Above-mentioned strain influenza virus, by being inoculated in the chick embryo allantoic cavity of 9 ages in days amplification, hatches 2d for 35 DEG C, gathers in the crops allantoic fluid.With
Mdck cell titration virus, judges the median infective dose (TCID of these strains with cytopathic-effect inhibition assay (CPE)50/ 100 μ L) make
For virus original titer.
1.1.4 reagent D MSO (SIGMA company of the U.S.)；MEM (GIBCO company of the U.S.) lot number: 8114414；Hyclone
(GIBCO company of the U.S.) lot number: 10099；PBS (GIBCO company of the U.S.) lot number: 20150122；1mg/ml TPCK lot number:
20140220 purchased from this bio tech ltd, prompt times of Guangzhou.MTT (3-(4,5-dimethylthiazole-2)-2) is purchased from
Genebase。
1.2. experimental technique
1.2.1 medicine dissolution indolal, dissolve with DMSO and be configured to working stocks (concentration 500mg/mL), put 4 DEG C of preservations；
Positive drug oseltamivir phosphate DMEM culture fluid dissolves, and filters rearmounted 4 DEG C of preservations.
1.2.2. Drug toxicity trails (mtt assay)
By every hole about 2.5 × 104Mdck cell is inoculated into 96 orifice plates, after 24h after cell grows up to monolayer, discards cultivation
Liquid, adds different dilution medicine 100 μ L/ hole, and blank and normal cell controls hole add 100 μ L/ hole MEM, 37 DEG C,
5%CO2Continuing to cultivate 36-48 hour, every hole adds MTT solution (5mg/mL) 20 μ L, puts 37 DEG C, 5%CO2Incubator continues hatch 4
Hour.Culture supernatant is abandoned in suction, and every hole adds 100 μ L dimethyl sulfoxide (DMSO), low-speed oscillation 10 minutes, makes crystal fully melt
Solve.Select 490nm wavelength, enzyme linked immunological monitor measures each hole absorbance value.
Calculate suppression ratio according to the following formula, and to calculate 50% toxic concentration by Reed-Muench method be that medicine half has
Poison concentration (TC50)。
Suppression ratio=[(normal group mean OD value-blank group mean OD value)-(administration group mean OD value-blank group is flat
All OD values)]/(normal group mean OD value-blank group mean OD value) × 100%.
1.2.3. vitro Drug anti-influenza virus activity is tested
As it is shown in figure 1, reduce the test method(s) research indolal suppression to influenza A H1N1 influenza virus (PR8) with cell plaque
Effect.Cover with mdck cell viral adsorption in 96 porocyte culture plates of monolayer 2 hours, concurrently set positive drug and cell
Comparison.After cell viral adsorption 2h, by drug dilution in 2X MEM (in addition to virus and cell controls), mix 1.6% agar,
Make its room temperature be cooled to 40 DEG C, add the TPCK pancreatin of final concentration of 1.5 μ g/mL, then mixed liquor is added in cell plates,
37 DEG C of 5%CO2It is inverted under environment and cultivates, cultivate 2-3 days, after white dot occurs, add the neutral blue dyestuff 37 diluted
DEG C effect 4 hours or overnight, calculates plaque number, and calculates the IC of medicine infected by influenza after dye extraction50。
1.2.4 the indolal In-vitro Inhibitory Effect to different subtype influenza virus
With cytopathic-effect inhibition assay (Cytopathic Effect Reduction Method) research indolal to difference
The inhibitory action of subtype influenza virus.Cover with mdck cell viral adsorption in 96 porocyte culture plates of monolayer 2 hours, simultaneously
Set positive drug and cell controls.Cell viral adsorption 2h, adds variable concentrations medicine (in addition to virus and cell controls) and exists
37 DEG C of 5%CO2Cultivate under environment.
There is lesion degree by following 6 grade standard records in cell :-normal for cell growth, occur without pathological changes；± for cell
Pathological changes is less than the 10% of whole cell monolayer；+ the 25% of whole cell monolayer is accounted for for cytopathy；++ account for for cytopathy
The 50% of whole cell monolayer；+++ accounting for the 75%:++++ of whole cell monolayer for cytopathy, to be that cytopathy accounts for whole
More than the 75% of cell monolayer.With Reed-Muench method calculation of half inhibitory concentration (IC50), and to select index SI to represent (SI
=TC50/IC50), SI > 2 represents that low toxicity is efficient；SI:1～2 represents high poison poor efficiency；SI < 1 represents invalid.
1.3. experimental result
1.3.1 cytotoxicity
Mtt assay is utilized to record the half poisonous concentration (TC of test medicine50) it is 335.57 μ g/mL；It is shown in Table 1.
1.3.2 the indolal In-vitro Inhibitory Effect to different subtype influenza virus
Plaque reduces result of the test and shows: indolal has inhibitory action to Influenza virus H1N1 (PR8), and medicine is 25
μ g/mL-100 μ g/mL significantly reduces the formation of influenza virus plaque.As shown in Figure 1.
1.3.3 vitro Drug suppression influenza virus drug effect
Cell phenotype conversion test result indicate that: indolal to multiple subtype influenza virus, wraps under treatment model
Including A type, Influenza B virus, influenza A virus includes that human influenza virus and bird flu virus all have inhibitory action, refers to table
1。
Table 1 indolal is external to different subtype influenza virus drug action
Note: select index (SI), SI > 2 represents that low toxicity is efficient；SI:1～2 represents high poison poor efficiency；SI < 1 represents invalid.
Test example 2 indolal suppresses the inflammatory reaction experiment that influenza virus mediates in human airway epithelial cells
2.1 experiment material
2.1.1 medicine given the test agent: indolal.
2.1.2 cell human airway epithelial cells (16HBE) is purchased from Chinese Academy of Sciences's Shanghai cell bank.
2.1.3 the common influenza A H1N1 influenza virus of Strain (A/PR/8/34, H1N1) is purchased from ATCC, with Reed-Muench
Method measures its infection multiplicity (M.O.I), using M.O.I=1 as virus titer infection cell.
2.1.4 reagent D MEM culture medium (lot number: 8114176)；PBS (lot number: 20150122), hyclone (lot number:
10099) GIBCO company it is purchased from；TPCK (lot number: 20140220) is purchased from this company of prompt times of Guangzhou.ELISA kit is bought certainly
RayBio company, Cat ELH-IP-10；ELH-CCL-5.
2.2 experimental technique
2.2.1 16HBE cell is cultivated
Normal person's human airway epithelial cells (16HBE) is inoculated in 100mm culture dish, uses 10%DMEM high glucose medium,
In 37 DEG C, 5%CO2, cultivate in cell incubation case under the conditions of saturated humidity, treat that cell grows into the logarithmic proliferation phase
Time, collect cell.After the cell collected is counted, with every hole 2 × 105The density of individual/mL is inoculated in diameter 15.6mm's
In 24 orifice plate Tissue Culture Dishs, basis of microscopic observation cell attachment, well-grown after 24 hours.Change 1%DMEM high glucose medium
Carry out next step virus after cell hunger being cultivated 24 hours and medicine irritation is tested, when adding stimulus object, cell culture medium is changed
Become the culture medium without hyclone.
2.2.2 virus and medicine irritation
After cell attachment 24 hours, PBS rinses 2 times, with the DMEM without serum by dilute for Influenza virus H1N1 (PR8)
Releasing to M.O.I=1, every hole adds 0.5mL virus liquid, and 37 DEG C adherent 2 hours.With without hyclone but containing 0.4ug/mL
The DMED of TPCR enzyme dilutes medicine, and every hole adds 1mL, collects cell supernatant after acting on 24 hours.
2.2.3 detection medicine is to 16HBE cell toxicity test (mtt assay)
16HBE cell is with every hole 2 × 105The density of individual/mL is inoculated in the 96 orifice plate Tissue Culture Dishs of diameter 6.94mm,
Basis of microscopic observation cell attachment, well-grown after 24 hours.The DMEM2 times of gradient dilution medicine without serum, effect 48 is little
Shi Hou, mtt assay (with above-mentioned) detection drug toxicity.
2.2.4 inflammatory factor protein ELISA method detection in cell culture medium
Operate according to ELISA kit product description:
1) reagent takes out and balances to room temperature, adds sample, and incubated at room 2.5 hours or 4 DEG C is overnight；
2) Washing buffer rinses 4 times；
3) the biotinylated antibdy100 μ L room temperature effect that addition has diluted 1 hour；
4) Washing buffer rinses 5 times, adds the Streptavidin solution100 μ L diluted, and room temperature is made
With 45 minutes；
5) TMB nitrite ion, room temperature reaction 30 minutes are added；The Stop Solution adding 500 μ L terminates reaction, all-wave
Long microplate reader reading (450nm), calculates the content of inflammatory factor albumen in sample according to standard curve.
2.3Experimental result
2.3.1 medicine is to 16HBE cell drug toxicity
After mtt assay detection medicine acts on 16HBE cell 48 hours, 400 μ g/mL concentration versus cell toxicity are big, 100 μ g/
ML to cell slightly toxicity, but to 16HBE cytotoxic below 50 μ g/mL concentration.As shown in Fig. 2 A.
2.3.2 the expression of the inflammatory factor of influenza virus mediation is suppressed after medicine effect 24 hours
Indolal is at the product that concentration is that 100 μ g/mL suppress inflammatory factor (such as IL-6, IP-10, RENTES etc.) significantly
Raw, when drug level is 100 μ g/mL, IL-6 albumen can be lowered the expression of about 70%, the expression to IP-10 albumen
Also having the attenuating of about 65%, the indolal of 200 μ g/mL reduces the expression of RENTES albumen 50% (comparing with virus group)
(as shown in Fig. 2 B, Fig. 2 C, Fig. 2 D).Result shows: medicine--indolal can effectively suppress the inflammation that influenza virus mediates in detection
The generation of inflammation factor.
The above, be only presently preferred embodiments of the present invention, and the present invention not does any pro forma restriction, therefore
All contents without departing from technical solution of the present invention, any simply repair made for any of the above embodiments according to the technical spirit of the present invention
Change, equivalent variations and modification, all still fall within the range of technical solution of the present invention.
Claims (10)
1. indolal application in the medicine of resisiting influenza virus and the diseases associated with inflammation of preparation treatment influenza virus mediation.
Application the most according to claim 1, it is characterised in that: described indolal has the son of suppression influenza virus in preparation
For the application in the medicine of the effect of virus replication and/or the inflammatory factor generation effect with suppression influenza virus mediation.
Application the most according to claim 1, it is characterised in that: described influenza virus is influenza A virus, influenza B
Virus or bird flu virus.
Application the most according to claim 3, it is characterised in that: described influenza virus be human influenza virus's H1N1 hypotype or
H3N2 hypotype or INF Type B；Described human influenza virus's H1N1 hypotype includes new influenza A H1N1 influenza virus；Or described influenza virus
For Avian Influenza Virus H9N2.
Application the most according to claim 1, it is characterised in that: described indolal is to extract from natural plants Radix Isatidis
's.
Application the most according to claim 1, it is characterised in that: the dosage form pharmaceutically allowed made by described medicine, described dose
Type is tablet or capsule.
Application the most according to claim 1, it is characterised in that: the influenza virus of inducing inflammatory reaction includes common A type
H1N1 influenza virus A/PR/8/34.
Application the most according to claim 2, it is characterised in that: described inflammatory factor includes IL-6, IP-10, RENTES.
9. one kind for treating influenza or the medicine of diseases associated with inflammation mediated by influenza virus, it is characterised in that: described medicine
Its active component includes the indolal as described in any one of claim 1～8.
Medicine the most according to claim 9, it is characterised in that: its active component of described medicine comprises 3-indolal.
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| CN110522749A (en) * | 2018-05-25 | 2019-12-03 | 中药质量研究国家重点实验室（澳门科技大学） | Application of the Radix Isatidis indolal in preparation antiviral drugs |
| CN110101720A (en) * | 2019-03-19 | 2019-08-09 | 雷允上集团药业有限公司 | Liushen Pills is preparing the application in the drug for preventing and treating influenza inflammation disease |
| CN110101720B (en) * | 2019-03-19 | 2023-08-01 | 雷允上药业集团有限公司 | Application of liushen pills in preparation of medicines for preventing and treating influenza inflammatory diseases |
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