CN108685900A - Applications of the atractylodes lactone III in anti-rotavirus - Google Patents

Applications of the atractylodes lactone III in anti-rotavirus Download PDF

Info

Publication number
CN108685900A
CN108685900A CN201810226597.XA CN201810226597A CN108685900A CN 108685900 A CN108685900 A CN 108685900A CN 201810226597 A CN201810226597 A CN 201810226597A CN 108685900 A CN108685900 A CN 108685900A
Authority
CN
China
Prior art keywords
rotavirus
drug
atractylodes lactone
lactone iii
cell
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201810226597.XA
Other languages
Chinese (zh)
Other versions
CN108685900B (en
Inventor
赵文昌
宋丽军
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Guangdong Medical University
Original Assignee
Guangdong Medical University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Guangdong Medical University filed Critical Guangdong Medical University
Priority to CN201810226597.XA priority Critical patent/CN108685900B/en
Publication of CN108685900A publication Critical patent/CN108685900A/en
Application granted granted Critical
Publication of CN108685900B publication Critical patent/CN108685900B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Virology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to atractylodes lactone III technical fields, and in particular to applications of the atractylodes lactone III in anti-rotavirus.Atractylodes lactone III anti-rotavirus application, specifically, applications of the atractylodes lactone III in the drug for preparing anti-rotavirus.Atractylodes lactone III the drug for preparing anti-rotavirus application, this be applicant study for the first time find atractylodes lactone III have the function of anti-rotavirus, filled up the blank of anti-rotavirus medicaments, had far-reaching significance and be worth.

Description

Applications of the atractylodes lactone III in anti-rotavirus
Technical field
The present invention relates to atractylodes lactone III technical fields, and in particular to applications of the atractylodes lactone III in anti-rotavirus.
Background technology
Rotavirus (Rotavirus, RV) is the main pathogens for leading to Acute Infantile Diarrhea, and there are about 600,000 every year Infant is dead because RV infects, and mainly in autumn and winter prevalence, happening and prevelence is not influenced by sanitary condition.Developed country's incidence It is not much different with developing country, but the death rate of developing country is significantly larger than developed country.RV generally passes through excrement-mouth way Diameter is propagated, 2~4 days incubation periods.Have previously been thought that RV mainly invades small intestine cells villus, the most important symptom of patient is diarrhea, is risen Sick anxious, day more than ten times to tens of times can occur specificity lgM, lgG antibody, enteron aisle office quickly with fever in blood after infection There is secreting type lgA in portion, virus can be neutralized, to homologous virus infected with effect.The course of disease 3~5 days or one week or so.Nearest grinds Study carefully and show that RV infection is not limited only to enteron aisle, can also invade other systems, cause many complication, such as shock, encephalopathy, heart damage Evil and extrahepatic bile ducts obstruction.
It there is no the specific medicament of prevention RV infection at present.And in terms of related RV vaccines, it is domestic to be still in conceptual phase, foreign countries It is expensive to list RV vaccine prices, the diversity of RV strains makes its prevention be limited in scope.Existing clinic mostly uses the oral benefit of WHO recommendations Liquid is to alleviate symptom.Thus, it is found that, exploitation safely and effectively medical treatment rotavirus infection it is extremely important.
Atractylodes lactone III, English name:Atractylenolide III (C15H20O3) are that (structural formula is such as white needles Under), it is the principle active component of composite family rhizoma atractylodis platymiscium Rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala Koidz.), has Effect that is anti-inflammatory, antitumor, improving dull-witted mouse model and adjusting gastrointestinal motility promote the functions such as absorption of nutrient ingredients, but have It is less to close the antiviral effect reports of atractylodes lactone III.
The structural formula of atractylodes lactone III.
Invention content
In view of the above-mentioned deficiencies in the prior art, it is an object of the present invention to provide applications of the atractylodes lactone III in anti-rotavirus.
To achieve the goals above, the present invention adopts the following technical scheme that:
Applications of the atractylodes lactone III in the drug for preparing anti-rotavirus is provided.
In the drug of the anti-rotavirus, the molar concentration of the atractylodes lactone III is 5umol/L~80umol/L.
In the drug of the anti-rotavirus, the atractylodes lactone III to cell generate toxicity molar concentration be more than 80umol/L。
The drug of the anti-rotavirus be tablet, granule, powder, capsule, pellet, liquid preparation, semisolid preparation, The preparation of nanometer, micro emulsion or liposome.
The drug of the anti-rotavirus includes the composition or compound preparation using atractylodes lactone III as component.
Compared with prior art, advantageous effect is the present invention:
The atractylodes lactone III of the present invention is in the application of anti-rotavirus, and atractylodes lactone III is in the medicine for preparing anti-rotavirus The application of object, be applicant study for the first time find atractylodes lactone III have the function of anti-rotavirus, filled up anti-rotavirus The blank of drug has far-reaching significance and is worth.
Description of the drawings
Fig. 1 is the cytotoxicity experiment result figure of atractylodes lactone III.
Fig. 2 is that the atractylodes lactone III of various concentration directly inactivates the experimental result picture of rotavirus.
Specific implementation mode
In order to make the technical problems, technical solutions and beneficial effects solved by the present invention be more clearly understood, below in conjunction with Drawings and examples, the present invention will be described in further detail.It should be appreciated that specific embodiment described herein is only used To explain the present invention, it is not intended to limit the present invention.
Embodiment 1.
Applications of the atractylodes lactone III of the present embodiment in the drug for preparing anti-rotavirus.Atractylodes lactone III is anti-in preparation The application of the drug of rotavirus, be applicant study for the first time find atractylodes lactone III have the function of anti-rotavirus, fill up The blank of anti-rotavirus medicaments, has far-reaching significance and is worth.
Embodiment 2.
Applications of the atractylodes lactone III of the present embodiment in the drug for preparing anti-rotavirus, wherein the medicine of anti-rotavirus In object, the molar concentration of atractylodes lactone III is 5umol/L~80umol/L.
Embodiment 3.
Applications of the atractylodes lactone III of the present embodiment in the drug for preparing anti-rotavirus, wherein the medicine of anti-rotavirus In object, the molar concentration that the atractylodes lactone III generates cell toxicity is more than 80umol/L.
Embodiment 4.
Applications of the atractylodes lactone III of the present embodiment in the drug for preparing anti-rotavirus.Wherein, the medicine of anti-rotavirus Object is the preparation of tablet, granule, powder, capsule, pellet, liquid preparation, semisolid preparation, nanometer, micro emulsion or liposome.
Embodiment 5.
Applications of the atractylodes lactone III of the present embodiment in the drug for preparing anti-rotavirus.Wherein, the medicine of anti-rotavirus Object includes the composition or compound preparation using atractylodes lactone III as component.
Experiment:
One, experiment material
Experimental drug:
Atractylodes lactone III (Chengdu Man Site Co., Ltds, purity 99.99%, lot number:MUST-17030203).Experiment examination Agent:
DMEM culture solutions, fetal calf serum are that GIBCO companies provide;
MTT (4,5, dimethylthiazole -2,5, diphenyltetrazolium bromide), M1124Amresco companies provide;
Pen .- Strep mixed solution, trypsase, PBS, dimethyl sulfoxide (DMSO) are that solarbio companies provide.
The preparation and packing of reagent:
(1) fetal calf serum is divided in the 50ml centrifuge tubes of sterilizing, -20 DEG C of preservations.
(2) trypsase is divided in the 10ml centrifuge tubes of sterilizing, -20 DEG C of preservations.
(3) mycin-streptomysin mixed solution is divided in the 10ml centrifuge tubes of sterilizing, -20 DEG C of preservations.
(4) MTT applications liquid:
MTT powder 50mg, PBS10ml, stirring and dissolving, 0.22 μm of filter membrane filtration sterilization, after packing -20 DEG C be kept in dark place it is standby With.
Experiment equipment:
96 porocyte culture plates, adjustable micro sample adding appliance, Tissue Culture Flask, filter, suction pipe, insulating box, sterilizing pan;
Clean operation console SIK-202 types, Bengbu cleaning equipment factory provide;
OLYMP Μ S inverted light microscopes CKX41;
Enzyme-linked immunosorbent assay instrument DG3022A;
Carbon dioxide incubator, Thermo companies of the U.S. provide;
Cell and virus;
Caco-2 cells (colon cancer cell), MA104 cells (rhesus embryonic nephrocyte), Wa plants of rotavirus.
Two, experimental method
(1) cell and virus:
Caco-2 cells and MA104 cells are containing 10% fetal calf serum, 100 μ/ml penicillin, 100 μ g/ml streptomysins It grows and passes in DMEM culture solutions.Virus infection is to adapt to Wa plants of rotavirus of people of cell culture proliferation.
(2) cytotoxicity experiment of drug:
Atractylodes lactone III solution is prepared:Atractylodes lactone III sample 2mg are weighed, after first using DMSO (dimethyl sulfoxide (DMSO)) dissolvings It is added with appropriate DMEM dissolvings, no more than 0.5% is standard with DMSO final concentrations, and solvent control group is set.Nothing in clean bench Bacterium operates disposable filter filtration sterilization.Calculate initial concentration.Various drug final concentration 5umol/L~640umol/L.
Cytotoxicity experiment:By Caco-2 cells with 6 × 104The cell density of a/ml is added in 96 porocyte culture plates Upper every 200 μ l of hole.37 DEG C of 5%CO2It is incubated to cell growth into single layer.Growth-promoting media is sucked out, first according to 1:1,1:10,1:100,1: 1000 ratio is diluted to obtain a series of liquid of concentration with the DMEM culture solutions without serum, and then 100 holes μ l/ are added Into 96 orifice plates, each concentration repeats 6 holes.Isometric DMEM maintaining liquids for being free of serum are only added in normal control.37 DEG C 5% CO2It is incubated, light microscope is observed continuously, if having cytotoxicity variation between the first, second concentration of drug within 72 hours Except its excess-three drug concentration cell it is normal.This shows effective concentration 1:1 and 1:Between 100.According to 1:1,1: 2,1:4,1:8,1:16,1:32,1:64,1:128 ratio obtains a series of concentration liquids, repeats aforesaid operations, optical microphotograph It is higher than 1 within being found 48 hours under mirror:There is cytotoxicity variation in 64 drug concentration.
37 DEG C of 5%CO2It is incubated, after 2d is observed continuously in light microscope, liquid is sucked out, is protected from light, is added 5mg/ml's The holes MTT25 μ l/ (are prepared, avoid light place) with the DMEM culture mediums without serum, 37 DEG C of 5%CO2Be incubated 4h after, 800r/ml from The heart abandons supernatant, and the holes DMSO50 μ l/ are added, vibrate about 10min at room temperature, after dissolving to be crystallized, mixing detects in microplate reader Optical density (optical density, OD) value under 490nm wavelength per hole.Cell survival rate is found out by following equation.
Cell survival rate %=medicine groups mean absorbance values/cell controls group mean absorbance values × 100%.
(3) virus multiplication and titer determination:
The proliferation and titer determination of Wa plants of RV carries out on MA104 cells.When cell grows to single layer in culture bottle It is inoculated with RV.Before virus inoculation, cell monolayer is first washed once with phosphate buffer (PBS, pH7), with serum-free DMEM culture solutions It washes twice.Before inoculation, protovirus liquid is taken out from -80 DEG C of refrigerators, 4 DEG C of dissolvings, 37 DEG C and 10 μ g/ml of pancreatin acts on 30min rinses the MA104 cells PBS for growing up to single layer twice.The virus liquid after being incubated with pancreatin, inoculation disease is then added Cell maintenance medium after poison is no fetal calf serum, contains the DMEM culture solutions of 1 μ g/ml pancreatin.Cell after virus inoculation puts 37 DEG C Carbon dioxide incubator is incubated in (containing 5% carbon dioxide), until virus infection MA104 cytopathies (CPE cytopathic Effect) reach +++ when, culture bottle is put into -20 DEG C and is frozen, then 4 DEG C melt, repeatedly freeze thawing three times, low-temperature and high-speed 12000r/min centrifuging and taking supernatants harvest virus liquid, then ibid method is repeated once virus passage assays in cell, harvest virus. Packing, -80 DEG C of preservations.
Virus infection titer is measured carries out (microtitrimetry) with MA104 cells in 96 well culture plates.With without The DMEM culture solutions of serum are by it according to 1:10 are diluted to 10-110-210-3…10-6Etc. series concentrations, single layer MA104 will be trained 96 orifice plates of cell are rinsed 2 times with PBS, then the virus of different dilutions are added in 96 porocyte culture plates, and 25 holes μ l/ are every A concentration repeats 8 holes.Normal control cells, 37 DEG C of 5%CO are set2Virus liquid is drawn out after being incubated 2h, is added without serum Cell culture fluid, 200 holes μ l/.37 DEG C of 5%CO2It is incubated, is observed continuously.When the minimum dilution of cytopathy CPE can occur Viral hole in when not continuing to occur CPE, count each dilution and the cell hole count of CPE occur, according to the sides nch Reed-M μ Method calculates the TCID of virus50(Tissue culture infective dose)。
(4) the anti-RV effects of drug:
In an experiment we select the concentration of drug TC90-95 to carry out following anti-RV experiments first, then will filter out After the drug for there are anti-RV effects, with DMEM culture solutions (being free of serum) doubling dilution, the anti-RV effects of various concentration are investigated.
(5) effect of the drug to virus absorption onto cell:
Liquid is added in 96 well culture plates of the Caco-2 cells for growing into single layer, each liquid repeats 6 holes, 100 μ l/ Hole.Normal cell controls group is set, and isometric DMEM culture solutions (being free of serum) are only added in virus control group.37 DEG C of 5%CO2 It is incubated 2h.
Liquid is sucked out, 100TCID is added in addition to Normal group50Virus (virus and the pancreatin of 10 μ g/ml concentration 37 DEG C of effect 30min) 100 holes μ l/, 37 DEG C of 5%CO2It is incubated 2h, virus is sucked out, 200 holes μ l/ of addition cell maintenance medium, 37 DEG C 5%CO2Incubation is observed continuously.
There is CPE when cell to exist ++-+++ when maintaining liquid is sucked out, the holes MTT50 μ l/ of 5mg/ml are added, after being incubated 2h Abandon supernatant.The holes DMSO25 μ l/ are added, shake mixing about 10min at room temperature.Enzyme-linked immunosorbent assay instrument, which is read, under subsequent 570nm inhales Shading value.
Drug is calculated according to the following formula to viral suppression and therapeutic index:
Drug is to viral suppression=(medicine group mean absorbance values-virus control group mean absorbance values)/(normal Cell controls group mean absorbance values-virus control group mean absorbance values) × 100%, repeat experiment three times.
Evaluation index is used as using therapeutic index (treatment index, TI), weighs inhibition effect of the drug to RV, TI=CC50/IC50.
Note:It observes under an optical microscope, no CPE is denoted as:—;There is CPE in 25% cell, is denoted as:+;25%- There is CPE in 50% cell, is denoted as:++;There is CPE in the cell of 50%-75%, is denoted as:+++;The cell of 75%-100% goes out Existing CPE, is denoted as:++++.
(6) direct deactivation of the drug to virus:
Drug is mixed in equal volume with the virus liquid (virus acts on 30min with the pancreatin of 10 μ g/ml concentration) of 100TCID50 Act on 2h.
It adds it in 96 well culture plates for growing into single layer Caco-2 cells, is before rinsed cell 2 times with PBS. Normal cell controls group is set, and isometric DMEM is only added in virus control group.37 DEG C of 5%CO2It is incubated 2h, then by mixed liquor It is sucked out, 200 holes μ l/ of cell maintenance medium, 37 DEG C of 5%CO is added2Incubation is observed continuously, and CPE occur when cell exists ++-+++ when Ibid method does MTT detections, and calculates inhibiting rate and therapeutic index of the drug to virus.
(7) effect that drug synthesizes viral organism:
(1) by 100TCID50Virus liquid (virus acts on 30min with the pancreatin of 10 μ g/ml concentration) be added to and grow into list 100 holes μ l/ in 96 well culture plate of Caco-2 cells of layer are before rinsed cell 2 times with PBS.If cell normal control, it is added Isometric DMEM culture solutions.37 DEG C of 5%CO2It is incubated 2h, then virus liquid is sucked out, 100 holes μ l/ of liquid are added, if virus is right According to isometric DMEM culture solutions are only added.
(2) 37 DEG C of 5%CO2It is incubated 2h, liquid is sucked out later, 200 μ of cell maintenance medium/hole, 37 DEG C of 5%CO are added2It incubates It educates and is observed continuously.
(3) i.e. cell CPE exists ++-+++ when according to upper method do MTT detections, and calculate drug to the inhibiting rate of virus and Therapeutic index.
(8) statistical analysis
Using SPSS13.0 softwares, One-Way ANOVA methods are selected, medication group OD values and model group OD values are subjected to mean Compare.The PROBIT Returns Law are selected, by drug concentration and cell survival rate, drug concentration carries out the inhibiting rate of virus with drug Regression analysis.Obtain the cell half survival concentration C C of drug50, inhibition concentration IC of the drug to virus infected cell half50, And according to therapeutic index TI=cell halves survival drug concentration/inhibition half virus drugs concentration, calculate therapeutic index.
Three, experimental result
(1) atractylodes lactone III cytotoxicity experiments result:
Atractylodes lactone III is shown in shown in attached drawing cytotoxic effect (n=3) experimental result of Caco-2, the results showed that white Art lactone II I does not occur cytotoxicity in 5~80umol/L of concentration, apparent cell occurs when concentration is more than 160umol/L Toxicity.
(2) atractylodes lactone III prevents the experimental result of rotavirus invasion cell:
MTT shows each drug concentration group OD values no significant difference compared with virus control group, P > 0.05 (n=3). The result shows that drug is without the effect for preventing rotavirus invasion cell.
(3) atractylodes lactone III directly inactivates the experimental result of rotavirus:
1 atractylodes lactone III of table is to the directly deactivation (n=3) of RV biologies
The result shows that with the raising (as shown in Figure 2) of atractylodes lactone III concentration within the scope of 40~70umol, it is straight The effect for meeting inactivation RV is bigger, show atractylodes lactone III directly inactivate the effect of RV with concentration increase and enhancing (in a certain range It is interior), but invade cytosis without rotavirus is prevented.
(4) effect that atractylodes lactone III synthesizes viral organism:
MTT shows each drug concentration group OD values no significant difference compared with virus control group, P > 0.05 (n=3). The result shows that drug to viral synthesis without positive effect.
The above results show that the effect of the anti-RV of atractylodes lactone III is to play to make by the direct killing approach to RV viruses With, the absorption and biosynthesis of RV are had no significant effect, the research for exploitation atractylodes lactone III provided as the new drug of anti-RV Experimental basis.
Finally it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention, rather than the present invention is protected The limitation of range is protected, although being explained in detail to the present invention with reference to preferred embodiment, those skilled in the art answer Work as understanding, technical scheme of the present invention can be modified or replaced equivalently, without departing from the reality of technical solution of the present invention Matter and range.

Claims (5)

1. atractylodes lactone III is in the application for the drug for preparing anti-rotavirus.
2. atractylodes lactone III according to claim 1 is in the application for the drug for preparing anti-rotavirus, it is characterised in that: In the drug of the anti-rotavirus, the molar concentration of the atractylodes lactone III is 5umol/L~80umol/L.
3. atractylodes lactone III according to claim 1 is in the application for the drug for preparing anti-rotavirus, it is characterised in that: In the drug of the anti-rotavirus, the molar concentration that the atractylodes lactone III generates cell toxicity is more than 80umol/L.
4. atractylodes lactone III according to claim 1 is in the application for the drug for preparing anti-rotavirus, it is characterised in that: The drug of the anti-rotavirus is tablet, granule, powder, capsule, pellet, liquid preparation, semisolid preparation, nanometer, micro- The preparation of breast or liposome.
5. atractylodes lactone III according to claim 1 is in the application for the drug for preparing anti-rotavirus, it is characterised in that: The drug of the anti-rotavirus includes the composition or compound preparation using atractylodes lactone III as component.
CN201810226597.XA 2018-03-19 2018-03-19 Application of atractylenolide III in resisting rotavirus Active CN108685900B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201810226597.XA CN108685900B (en) 2018-03-19 2018-03-19 Application of atractylenolide III in resisting rotavirus

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810226597.XA CN108685900B (en) 2018-03-19 2018-03-19 Application of atractylenolide III in resisting rotavirus

Publications (2)

Publication Number Publication Date
CN108685900A true CN108685900A (en) 2018-10-23
CN108685900B CN108685900B (en) 2020-08-04

Family

ID=63844311

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201810226597.XA Active CN108685900B (en) 2018-03-19 2018-03-19 Application of atractylenolide III in resisting rotavirus

Country Status (1)

Country Link
CN (1) CN108685900B (en)

Also Published As

Publication number Publication date
CN108685900B (en) 2020-08-04

Similar Documents

Publication Publication Date Title
CN102688332B (en) A kind of Chinese medicine composition for the treatment of flu and preparation method thereof
CN108371664A (en) Wogonoside is in the application for preparing anti-rotavirus medicaments
CN104586873B (en) Application of the oroxin A in treating cancer medicine is prepared
CN108836962A (en) Wogonin is in the application for preparing anti-rotavirus medicaments
CN108379280A (en) Scutelloside is in the application for preparing anti-rotavirus medicaments
CN108685900A (en) Applications of the atractylodes lactone III in anti-rotavirus
CN103070870B (en) Application of carbenoxolone in preparing anti-dengue virus medicine
CN106038536B (en) Application of the Columbianedin in pharmacy
WO2006104292A1 (en) Pharmaceutical composition comprising arsenic acid, meta-arsenite, and pharmaceutically acceptable salts
CN107041881A (en) Application of the calycosin in anti-rotavirus medicaments are prepared
CN102283838A (en) Application of ethoxysanguinarine to pharmacy
CN102920944A (en) Application of Shuqing granules in preparing medicine for resisting hand-foot-and-mouth disease pathogens
CN101104065A (en) Traditional Chinese medicine preparation for preventing respiratory viral infection disease and preparation method
CN105002144A (en) Bacteriophage capable of entering blood through oral administration and application of bacteriophage
CN102091091A (en) Application of lignosulfonate and pharmaceutical composition thereof
CN102440988A (en) Application of arbidol hydrochloride in preparation of anti-enterovirus medicines
CN105012201B (en) The oral care product with anti-helicobacter pylori of the alcohol extract containing Chinese hawthorn seed
Peries et al. Global eradication of Guinea worm
CN101843612B (en) Application of isoorientin in preparation of medicament for resisting respiratory syncytial virus
CN114452273B (en) Application of iodized hydrazide and iodized hydrazide polyacid derivative in preparation of CVB3 virus resistant drugs
CUTTING et al. The alleged efficiency of medicinal treatment of typhoid carriers
CN114796247B (en) Application of secoisolariciresinol diglucoside in preparation of rotavirus resistant medicine
CN111701003A (en) Application of Huoxiang Zhengqi compound in preparation of external washing and protecting product
CN101244050A (en) Application of combination with a plurality of components in medicaments for tuberculosis and white plague
CN105055504A (en) Feed additive compound essential oil for preventing diarrhea of pigeons as well as preparation method and application of essential oil

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant