CN103501798A - Pandemic influenza antiviral agent - Google Patents
Pandemic influenza antiviral agent Download PDFInfo
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- CN103501798A CN103501798A CN201280020117.5A CN201280020117A CN103501798A CN 103501798 A CN103501798 A CN 103501798A CN 201280020117 A CN201280020117 A CN 201280020117A CN 103501798 A CN103501798 A CN 103501798A
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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)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
- A61K36/732—Chaenomeles, e.g. flowering quince
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- 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
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
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Abstract
A pandemic influenza antiviral agent, containing as an active ingredient an extract obtained by extracting Chinese quince using 50% ethanol-water and purifying the extract solution by column fractionation.
Description
Technical field
The anti-new type influenza viral agent that the inhibiting extract that derives from plant of infection that the present invention relates to have new type influenza virus is effective ingredient, new type influenza virus hemagglutination inhibitor, the new type influenza virus adsorption inhibitor to cell.
Background technology
Annual influenza virus that all can trigging an influenza pandemic is the tunicary RNA viruses of tool that diameter is ten thousand/millimeter.Be divided into A type, B-mode, this 3 type of the third type according to its antigenic difference, what Epidemic Scope was wider is A type, B-mode.The viral particle surface at these, these 2 kinds of glycoproteins of hemagglutinin (HA) and neuraminidase (NA) are furcella shape projection, and there is the gene RNA that merogenesis is 8 in inside.The HA and the NA that are positioned at virus surface undergo mutation continually in same hypotype, every year all occurs new antigenic mutation strain.
The influenza virus that discharges of the spittle by cough is from people's nose or mouthful invade, and is adsorbed in the mucomembranous epithelial cell of upper respiratory tract by the furcella shape glycoprotein h A on viral top layer, starts propagation after invading in cell.By research in recent years, known viral infection mechanism.The receptors bind that the sugar chain on the viral target cell top layer with being present in the people forms, endosome is ingested, fusion by viromembrane and endosome film invades in cell, through shelling, migration, start the expression of viral gene and copy, finally breeding by from sprouting of host cell membrane, forming the progeny virus particle.
The symptoms such as unexpected heating, headache, arthralgia, malaise, appear in a few days from the infection of influenza virus, and follow the respiratory apparatus symptoms such as appearance is coughed or had sore throat, nasal mucus, nasal obstruction.Different from so-called flu, it is characterized in that appeal is strong, cause in a short time the popular of explosion type.In addition, the structure of the HA albumen of influenza virus is all undergone mutation every year repeatedly, and the antibody that the infection in past produces is also the main cause that infects diffusion without too large effect.
In order to suppress the infection of influenza virus, can consider obstruction to epithelial absorption, to the obstruction of the inhibition of transcribing and copying of the obstruction of the intrusion of cell, gene, protein synthesis, from inhibition of the release of cell etc., all become respectively the target spot of antiviral agents.So far, developed the antiviral agents such as amantadine, rimantadine, zanamivir, but reported the side effect such as anaphylaxis, Spirit nerve symptoms of disease, digestive organs systemic symptom, autonomic nervous system symptom, must add to note for its application.
In addition, influenza virus infects, breeds in the respiratory mucosa epithelium, can't accurately estimate popular type then, so the inoculation by vaccine suppresses to infect, also is considered to very difficult.Gargle frequently, avoid the drying of throat, sufficient nutrition and rest etc. to be considered to the most effective preventive measure at present.Expect to develop infect that inhibition is good and safety is no problem, can Anti-influenza virus agent used in everyday.
In recent years, as the influenza raw material in natural goods source, report has the polyphenol component (non-patent literature 1 and 2) of tea or black tea, and human trial shows, the viral infection (non-patent literature 3) of with black tea, gargling and can suppress actual.In addition, reported that the flavonoid composition from Radix Scutellariae demonstrates influenza infection inhibition (non-patent literature 4) by viral sialidase inhibitory activities.In addition, also reported the antiviral effect of Guizhier Yuebiyi Decoction (patent documentation 1) as Chinese medicine preparation, black currant extract (patent documentation 2), Rhizoma Solani tuber osi anthocyanin (patent documentation 3), Folium Psidii Guajavae extract (patent documentation 4), Herba Apocyni veneti extract (patent documentation 5), Olive leaf P.E (patent documentation 7) etc.
In addition, for rosaceous plant, announcement has take the influenza agent (patent documentation 6) that the extract of its bud or flower lobe is effective ingredient, has reported resisiting influenza virus effect, the Fructus Chaenomelis separator based on the plaque test method(s) inhibition (non-patent literature 7) for the erythrocytic coagulation caused by influenza virus to the infection inhibition (non-patent literature 6) of new type influenza virus and Fructus Chaenomelis extract of column chromatography separator (patent documentation 9, non-patent literature 5) of extract (patent documentation 8), the Fructus Chaenomelis of Fructus Chaenomelis.
Fructus Chaenomelis (Chaenomeles sinensis) is to originate in Chinese deciduous tree, and fruit section makes papaya wine, preserve, syrup etc. and comes edible.Its fruit be called as papaw (Japanese: メ イ サ), be mixed with drug effect and be eliminate the phlegm, the Chinese medicine of antitussive, analgesia etc.People carry out the evaluation of the active ingredient in pawpaw fruit, reported the antibiotic property composition of the triterpeness such as oleanolic acid as the micrococcus scarlatinae (Streptococcus pyogenes) of the pathogen for as pharyngitis, reported that the high-molecular weight polyphenol class is as the anti-inflammatory composition.The inventor has reported red cell agglutination inhibition and the infection inhibition (patent documentation 9) of the high-molecular weight polyphenol class in the pawpaw fruit to the seasonal current Influenza Virus.
Yet, there is not yet the effect of the erythrocytic coagulation that the inhibition of the column chromatography separator of the Fructus Chaenomelis of disclosing in relevant patent of the present invention causes by new type influenza virus and the new type influenza virus report to the absorption inhibition of cell, this is taken the lead in illustrating by the present invention.Influenza is all popular repeatedly every year, causes sometimes worldwide being very popular that is called as flu outbreak (pandemic).In March, 2009, the influenza caused by the H1N1 new virus that Mexico is that the beginning occurs of take is also one of them.This time, for new type influenza virus A/Chiba/1001/2009 (H1N1) pdm, confirm that Fructus Chaenomelis extract has the red cell agglutination inhibition and infects inhibition.
The prior art document
Patent documentation
Patent documentation 1: Japanese patent laid-open 6-199680 communique
Patent documentation 2: Japanese Patent Laid-Open 2000-212092 communique
Patent documentation 3: Japanese Patent Laid-Open 2001-316399 communique
Patent documentation 4: Japanese Patent Laid-Open 2000-273048 communique
Patent documentation 5: Japanese patent laid-open 11-71296 communique
Patent documentation 6: Japanese Patent Laid-Open 2002-145790 communique
Patent documentation 7: the special table of Japan Patent 2002-020305 communique
Patent documentation 8: Japanese Patent Laid-Open 2005-343836 communique
Patent documentation 9:PCT/JP2010/005762 description
Non-patent literature
Non-patent literature 1: infect disease and learn magazine, 68 (7) 824-829 (1994)
Non-patent literature 2: infect disease and learn magazine, 70 (11) 1190-1192 (1996)
Non-patent literature 3: infect disease and learn magazine, 71 (6) 487-494 (1997)
Non-patent literature 4:Chem.Pharm.Bull.38 (5) 1329-1332 (1990)
Non-patent literature 5:Journal of Ethnopharmacology, 118,108-112 (2008)
Non-patent literature 6:Food news, 43 (1) 155-157 (2009)
Non-patent literature 7:J Agric.Food Chem.53,928-934 (2005)
Summary of the invention
Invent technical problem to be solved
The objective of the invention is with safe plant extract that can daily relieved use a kind of new type influenza inhibitors of viral infection is provided, the erythrocytic aggregation inhibitor that caused by new type influenza virus, new type influenza virus be to the adsorption inhibitor of cell.
The technical scheme that the technical solution problem adopts
In order to solve above-mentioned problem, the inventor is conceived to have no side effect, safe Fructus Chaenomelis, discovery is added with Fructus Chaenomelis extract in the mdck cell of new type influenza virus, the red cell agglutination inhibition to new type influenza virus that is the component that is rich in polyphenol (CSD3) in pawpaw fruit for the infectivity neutralization activity of new type influenza virus A/Chiba/1001/2009 (H1N1) pdm and Fructus Chaenomelis separator (CSD3), thereby completed the present invention.
; the present invention is hemagglutination inhibitor in new type influenza inhibitors of viral infection, new type influenza virus infected cell, the new type influenza virus adsorption inhibitor to cell; it is characterized in that; extract with Fructus Chaenomelis (Chaenomeles sinensis, Pseudocydonia sinensis) is effective ingredient.The present invention still contains the diet product of the anti-new type influenza virus function of having of Fructus Chaenomelis extract.
The effect of invention
The invention provides take safe Fructus Chaenomelis extract as effective ingredient, for new type influenza virus effect very strong influenza virus-infection inhibitor, hemagglutination inhibitor in the influenza infection cell, the new type influenza virus adsorption inhibitor to cell.In addition, safe as the Fructus Chaenomelis extract of effective ingredient of the present invention, thus can by absorption, soak containing, make an addition to mask, air conditioner filter screen, clothes, wet paper towel, spray liquid etc. and as the application in daily life widely of new type influenza Gene therapy articles for use.In addition, also can add in the diet product such as chewing gum, confection, pressed candy, beverage, as the diet product with anti-new type influenza virus function, carry out daily utilization, picked-up.The treatment of the disease that the present invention causes infection mitigation and the new type influenza virus of new type influenza virus is effective.
The accompanying drawing explanation
Fig. 1 means the figure of the red cell agglutination inhibition of Fructus Chaenomelis extract CSD3.
Fig. 2 means the figure of the infectious neutralization of A/Chiba/1001/2009 (H1N1) pdm of Fructus Chaenomelis extract CSD3 active (plaque method).
Fig. 3 means the active (TCID of the infectious neutralization of A/Chiba/1001/2009 (H1N1) pdm of Fructus Chaenomelis extract CSD3
50method) figure.
The specific embodiment
In Fructus Chaenomelis as raw material of the present invention, be better to use its fruit.
The method that obtains extract of the present invention for the ground product by above-mentioned plant is not particularly limited, add the one kind or two or more mixed solvent in the organic solvents such as the lower alcohols such as water, methanol, ethanol, normal propyl alcohol and n-butyl alcohol, ether, ethyl acetate, acetone, glycerol, propylene glycol, extract by the extracting method that adopted in the past.But, if consider by orally ingestible Anti-influenza virus agent of the present invention, from the angle of safety, be better to use ethanol or its mixed liquor to extract.
As extraction conditions, be not particularly limited, be better about 50～90 ℃, 1～5 hour.After can using and filtering extracting solution and heat up in a steamer and extract solvent, under reduced pressure concentrate or lyophilization and must goods.In addition, also can use by the goods that organic solvent distributes, column chromatography etc. obtains these extract separation and purification.
For the form of utilizing of the present invention, be not particularly limited, can make powder, tablet by adding solvent, dispersant, formulation carrier, emulsifying agent, diluent, stabilizing agent etc. in the plant extract to as the effective ingredient example, containing the preparation arbitrarily such as tablet, inhalant, collutory, gargarism, suppository, injection, but route of administration example oral administration, respiratory tract administration, intravenous administration, rectally, subcutaneous administration, intradermal administration etc.At this moment, be better 10～2000mg/ days to the dosage of being grown up for each extract, but be not limited in this value.Addition as from extract to various preparations, according to the form of said preparation and difference, preferably with more than 0.001 % by weight, better be that approximately the ratio more than 0.01 % by weight is added.
In addition, contain by the present invention being adsorbed, soaking, make an addition to mask, air conditioner filter screen, clothes, wet paper towel, spray liquid etc., can provide the infection that is beneficial to the influenza prevention and suppress articles for use.The absorption of the plant extract in these purposes, addition infect according to this form that suppresses articles for use and difference can't be lumped together, preferably with the ratio interpolation of 0.001～5 % by weight.
In addition, of the present invention safe, so can be incorporated in following diet product, utilize in daily life: snacks such as chewing gum, confection, pressed candy, soft sweet, chocolate, cookies, the cold drinks such as ice cream, popsicle, beverage, soup, the diet product such as fruit jam.As addition, utilize the taste of form and extract and difference according to it, preferably with respect to the diet product with 0.001～5 % by weight, better be that the ratio of approximately 0.01～1 % by weight is added.
Embodiment
Below, exemplify embodiment, test example is specifically described the present invention, but the present invention is not limited in these examples.
[embodiment 1]
Cell strain and viral preparation
Cell is used (MDCK) cell of beagle nephrocyte (Mardin-Darby canine kidney), with the eagle's minimal essential medium containing 10% hyclone (Eagle ' s minimum essential medium), (EMEM) cultivates.Influenza virus is used A/Udorn/307/72 (H3N2) and A/Chiba/1001/2009 (H1N1) pdm.A/Udorn/307/72 is seeded in growth egg (eggs of 11 days) allantocherion intracavity and makes its propagation, with Temperature-Sensitive Mutants of Influenza A/Udorn/72 (H3N2) Virus.Virology117, in 45-61 (1982), the method for record is carried out purification.A/Chiba/1001/2009 (H1N1) pdm strain is inoculated in mdck cell, at carbon dioxide culture machine (37 ℃, 5%CO
2) internal breeding 2 days.With 5000rpm centrifugal 5 minutes, using this supernatant as virus liquid.
[embodiment 2]
The purification of the active component in Fructus Chaenomelis
The dry fruit of Fructus Chaenomelis (C.sinensis Koehne) obtains from the market in Chinese Hubei Province.By 50% ethanol (700ml) reflux, extract, for dry fruit 100g 1 hour, after filtration, by extracting solution concentrating under reduced pressure and lyophilization, thereby 50% ethanol extraction (CSE50) that obtains Fructus Chaenomelis (23g).Water suspends CSE50, use Diaion HP-20 (Mitsubishi Chemical) column chromatography (post: 8 * 15cm), with aquiferous ethanol (0%, 20%, 40%, 60%, the 100% ethanol) eluting of 5 grades, obtain CSD1 (water elution component: 14.5g), CSD2 (20% ethanol elution component: 3.2g), CSD3 (40% ethanol elution component: 3.7g), CSD4 (60% ethanol elution component: 161mg), CSD5 (100% ethanol elution component: 161mg) 5 parts.Use (-)-epicatechin as standard, by vanillin-salt acid system, the condensed type polyphenol in various piece is carried out quantitatively.
[embodiment 3]
The mensuration that the polyphenol content of each Fructus Chaenomelis separator and infection neutralization are tired
The infection neutralization of each component is tired and is used A/Udorn/307/72 (H3N2) to measure by the plaque method.Add 10 times of gradient dilution liquid of separator of equivalent in the virus liquid (1000PFU/ml) of 0.1ml, at room temperature react 30 minutes, 100 μ l are inoculated in to mdck cell (6 orifice plate), at room temperature adsorb 60 minutes.After absorption, add Leibovitz ' sL-15 culture medium (biotechnology Japanese firm (Life Technologies Japan the Ltd.)) 1.6ml containing 0.6% agarose, 1.5% gelatin, 2.5 μ g/ml pancreatin, solidify.Under 34 ℃, cultivate after 3 days, the plaque number that instrumentation occurs, obtain in 50% infection and concentration (IC
50).That the dilution of virus and separator is used is TGS (25mMTris, 140mM sodium chloride, 5mM potassium chloride, 0.7mM sodium phosphate 12 hydrates, 5.6mM glucose, pH7.4).
As described in Example 2, use DiaionHP-20 by 50% ethanol extraction of Fructus Chaenomelis the aquiferous ethanol eluting with 5 grades, be separated into CSD1～5, the each several part of gained is in 50% infection of A/Udorn/307/72 (H3N2) and IC
50be shown in table 1 with polyphenol content.The CSD3 component has the highest infection inhibition (IC
50=0.8 μ g/ml).In addition, the polyphenol content of CSD3 is 53.8%, is the highest.
So, in subsequent experimental, with CSD3, estimate the antiviral effect to new type influenza virus A/Chiba/1001/2009 (H1N1) pdm.
[table 1]
The polyphenol content of Fructus Chaenomelis separator
A; During 50% of A/Udorn/307/72 is infected and concentration
B; Epicatechin conversion, n=3, meansigma methods ± standard deviation
[embodiment 4]
The red cell agglutination of new type influenza virus A/Chiba/1001/2009 (H1N1) pdm that CSD3 is processed reduces test
The tire mensuration of (HA tires) of red cell agglutination is carried out with 96 orifice plates.The CSD3 for preparing each concentration with phosphate buffer normal saline processes viral 2 times of gradient dilution liquid series (50 μ l), add 0.5% (v/v) chicken red blood cell, 50 μ l, under 4 ℃ after standing 1 hour, judge having or not of red cell agglutination, the inverse that will present the high dilution of coagulation is tired as the HA of each virus liquid.Fructus Chaenomelis CSD3 component is tired to reduce to test by HA to the red cell agglutination inhibition of new type influenza virus A/Chiba/1001/2009 (H1N1) pdm and is estimated.At the virus liquid of 0.1ml, (HA tires: add the CSD3 liquid (0: contrast, 0.1,2,10,50,500 μ g/ml) of equivalent 32), after at room temperature reacting 60 minutes, measure HA and tire.
According to the method described above, tire and reduce test and estimate CSD3 and process the red cell agglutination inhibition to A/Chiba/1001/2009 (H1N1) pdm by red cell agglutination.The hemagglutinin of hemagglutination test (HA test) based on virus surface reacts with erythrocytic receptors bind, is the test of estimating viral receptor binding capacity.Can observe the erythroagglutination of CSD3 itself with the CSD3 more than 50 μ g/ml, therefore the red cell agglutination of A/Chiba/1001/2009 (H1N1) pdm being tired, with 25 μ g/ml, following CSD3 carries out in the minimizing test.At 1 μ g/ml, when following, the HA of virus tires and is similarly 16 with non-processing virus, does not observe the minimizing that red cell agglutination is tired.Be 8 in the processing of 5 μ g/ml, be reduced to 1/2.While being 25 μ g/ml, be reduced to lower than detectability (2) (Fig. 1).According to above result, can confirm the Fructus Chaenomelis separator to the red cell agglutination inhibition of new type influenza, new type influenza virus the absorption inhibition to cell.
[embodiment 5]
CSD3 reduces test to the infectious titer of new type influenza virus A/Chiba/1001/2009 (H1N1) pdm
Fructus Chaenomelis CSD3 component reduces to test by infectious titer to the infectious neutralization of new type influenza virus A/Chiba/1001/2009 (H1N1) pdm to be estimated.Virus liquid (2 * 10 at 0.1ml
7pFU/ml, HA tire: the CSD3 liquid (0: contrast that adds equivalent 32), 0.1,2,10,50,500 μ g/ml), at room temperature react 60 minutes, by plaque method and tissue culture infective dose (Tissue Culture Infectious Dose50%) (TCID
50) method mensuration infectious titer.
I) adopt the mensuration of plaque method
The CSD3 for preparing each concentration processes 10 times of gradient dilution liquid series of virus, and 100 μ l are inoculated in to mdck cell (6 orifice plate), by said method, counts plaque.Infectious titer means with PFU (plaque forming unit (plaque forming units))/ml.
Ii) adopt TCID
50the mensuration of method
The CSD3 for preparing each concentration with the MEM containing 2.5 μ g/ml pancreatin processes 10 times of viral gradient dilution liquid series, and 200 μ l are inoculated in to mdck cell (24 orifice plate), in the carbon dioxide culture machine, in 37 ℃, cultivates 3 days.After cultivation, according to the hemagglutination activity in supernatant have or not to judge infection, obtain TCID
50amount.
According to the method described above, estimate the infection neutralization by the infectious titer minimizing test that adopts the plaque method active.The infectious titer of untreated virus is 1.0 * 10
7pFU/ml.Process by CSD3, in the mode of dose-dependent, confirm the infection inhibition, when when during 1 μ g/ml, infectious titer is reduced to approximately 2/3,25 μ g/ml, infectious titer is reduced to approximately 1/60,250 μ g/ml, infectious titer is reduced to approximately 1/10000 (Fig. 2).But, because minimum plaque is many, be difficult to accurate instrumentation, so by adopting TCID
50the infectious titer of method reduces test and is estimated.
TCID
50the measurement result of method is, during the CSD3 of 1 μ g/ml processes, infectious titer is suppressed to approximately 1/3, during 5 μ g/ml, when infectious titer is suppressed to approximately 1/10,25 μ g/ml, when infectious titer is suppressed to approximately 1/100,250 μ g/ml, infectious titer is suppressed to 1/3000 (Fig. 2).In addition, with TCID
50evaluation carry out TCID by the observation of the cytopathic effect under microscope (Cytopathic effect:CPE) simultaneously
50evaluation, result is in full accord.
During the CSD3 of 5 μ g/ml processes, the minimizing that red cell agglutination is tired is about 1/2, and the minimizing of infectious titer is about 1/10.The minimizing of infectious titer is 5 times of the red cell agglutination minimizing of tiring, and this is prompting just, and CSD3 mainly suppresses the later virus multiplication process of absorption of new type influenza virus A/Chiba/1001/2009 (H1N1) pdm.
From above result, red cell agglutination inhibition activity and the active result of infectious neutralization with the active component CSD3 in Fructus Chaenomelis, estimated new type influenza virus A/Chiba/1001/2009 (H1N1) pdm are, the red cell agglutination of the virus after processing with the CSD3 of 5 μ g/ml is tired and is reduced to approximately 1/2, and infectivity is reduced to approximately 1/10.In the processing of 250 μ g/ml, infectious titer is reduced to 1/3000.These results mean, the anti-influenza virus activity composition in Fructus Chaenomelis is also effective for H1N1 new type influenza virus.Also have, because on the minimizing that infective minimizing is tired in red cell agglutination, so there be the inhibitory action of viruses adsorption after the stage in prompting.
Use the Fructus Chaenomelis extract of making in embodiment 1 to prepare collutory, inhalant, contain tablet, spray liquid, chewing gum, confection, pressed candy, beverage, powder agent, tablet, gargarism, soft sweet, chocolate, cookies, ice cream, popsicle, soup, fruit jam, wet paper towel, mask.Below, as embodiment, its formula is shown.
[embodiment 6]
The formula of collutory
[embodiment 7]
The formula of inhalant
[embodiment 8]
Formula containing tablet
[embodiment 9]
The formula of spray liquid
[embodiment 10]
The formula of chewing gum
[embodiment 11]
The formula of confection
[embodiment 12]
The formula of pressed candy
[embodiment 13]
The formula of beverage
[embodiment 14]
The formula of powder agent
[embodiment 15]
The formula of tablet
[embodiment 16]
The formula of gargarism
[embodiment 17]
The formula of soft sweet
The probability of utilizing on industry
The present invention can by absorption, soak containing, make an addition to mask, air conditioner filter screen, clothes, wet paper towel, spray liquid etc. and as new type influenza Gene therapy articles for use widely in daily life the application.In addition, also can add in various diet product, as the diet product with anti-new type influenza virus function, carry out daily utilization, picked-up.The treatment of the disease that the present invention causes infection mitigation and the new type influenza virus of new type influenza virus is effective.That is,, as the infection mitigation raw material, can expect the raw-material application as new product development.
The application advocates the priority of No. 2011-098230th, the Japanese patent application that proposes on April 26th, 2011, quotes the part of its content as the application.
Claims (5)
1. anti-new type influenza viral agent, is characterized in that, with the extract of Fructus Chaenomelis (Chaenomeles sinensis, Pseudocydonia sinensis), is effective ingredient.
2. anti-new type influenza viral agent, is characterized in that, Fructus Chaenomelis is extracted with 50% ethanol water, and this extracting solution is carried out to the column chromatography separation and purification, and the extract of gained of take is effective ingredient.
3. the erythrocytic aggregation inhibitor caused by new type influenza virus, is characterized in that, Fructus Chaenomelis is extracted with 50% ethanol water, and this extracting solution is carried out to the column chromatography separation and purification, and the extract of gained of take is effective ingredient.
4. the adsorption inhibitor of new type influenza virus to cell, is characterized in that, Fructus Chaenomelis is extracted with 50% ethanol water, and this extracting solution is carried out to the column chromatography separation and purification, and the extract of gained of take is effective ingredient.
5. the diet product, is characterized in that, containing Fructus Chaenomelis extract, has anti-new type influenza virus function.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2011-098230 | 2011-04-26 | ||
| JP2011098230A JP2012229178A (en) | 2011-04-26 | 2011-04-26 | Pandemic influenza antiviral agent |
| PCT/JP2012/002772 WO2012147327A1 (en) | 2011-04-26 | 2012-04-23 | Pandemic influenza antiviral agent |
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| Publication Number | Publication Date |
|---|---|
| CN103501798A true CN103501798A (en) | 2014-01-08 |
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| CN201280020117.5A Pending CN103501798A (en) | 2011-04-26 | 2012-04-23 | Pandemic influenza antiviral agent |
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| JP (1) | JP2012229178A (en) |
| KR (1) | KR20140023357A (en) |
| CN (1) | CN103501798A (en) |
| TW (1) | TW201304797A (en) |
| WO (1) | WO2012147327A1 (en) |
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| WO2020050633A1 (en) * | 2018-09-04 | 2020-03-12 | 한국식품연구원 | Composition for improving respiratory disease including extract of paliurus ramosissimus (lour.) poir. |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005343836A (en) * | 2004-06-04 | 2005-12-15 | Lotte Co Ltd | Anti-influenza virus agent, and infection inhibiting article containing the same and food and drink |
| CN1931320A (en) * | 2006-10-13 | 2007-03-21 | 解会元 | Medicinal wine composition and its prepn process |
| WO2011036883A1 (en) * | 2009-09-24 | 2011-03-31 | 株式会社ロッテ | Anti-influenza virus agent |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5117644B2 (en) * | 2000-11-06 | 2013-01-16 | 丸善製薬株式会社 | Preventive agent against influenza virus infection |
-
2011
- 2011-04-26 JP JP2011098230A patent/JP2012229178A/en not_active Withdrawn
-
2012
- 2012-04-23 KR KR1020137030181A patent/KR20140023357A/en not_active Application Discontinuation
- 2012-04-23 CN CN201280020117.5A patent/CN103501798A/en active Pending
- 2012-04-23 WO PCT/JP2012/002772 patent/WO2012147327A1/en active Application Filing
- 2012-04-26 TW TW101114914A patent/TW201304797A/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005343836A (en) * | 2004-06-04 | 2005-12-15 | Lotte Co Ltd | Anti-influenza virus agent, and infection inhibiting article containing the same and food and drink |
| CN1931320A (en) * | 2006-10-13 | 2007-03-21 | 解会元 | Medicinal wine composition and its prepn process |
| WO2011036883A1 (en) * | 2009-09-24 | 2011-03-31 | 株式会社ロッテ | Anti-influenza virus agent |
Non-Patent Citations (1)
| Title |
|---|
| REIKO SAWAI, ET AL.: "Anti-influenza virus activity of Chaenomeles sinensis", 《JOURNAL OF ETHNOPHARMACOLOGY》 * |
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|---|---|
| TW201304797A (en) | 2013-02-01 |
| WO2012147327A1 (en) | 2012-11-01 |
| KR20140023357A (en) | 2014-02-26 |
| JP2012229178A (en) | 2012-11-22 |
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