JPWO2006115123A1 - Virus inactivating agent - Google Patents

Abstract

The present invention relates to a virus inactivating agent comprising a proanthocyanidin-based polyphenol having an inactivating (preventing infection) effect against a virus such as influenza virus, particularly preferably a polyphenol obtained from unripe apple or hop cake. According to the virus inactivating agent of the present invention, the effect of inactivating (preventing infection) influenza virus is effectively exhibited by the action of polyphenols derived from or contained in apples or polyphenols derived from or contained in hops.

Description

The present invention relates to a virus inactivating agent which is a proanthocyanidin-based polyphenol having an inactivating effect on a virus such as influenza virus, particularly preferably a polyphenol derived from apple immature fruit or hop koji.
This application claims priority based on Japanese Patent Application No. 2005-121343 for which it applied to Japan on April 19, 2005, and uses the content here.

Until now, natural substances having antiviral activity have been studied. As such substances, there is a proanthocyanidin polymer (see Patent Document 1). The polymer is a proanthocyanidin polymer having 2 to 30 flavonoid units obtained from a plant called Croton recleri, and is said to be effective for treating respiratory virus infections such as influenza. Specifically, this document describes the therapeutic effect of proanthocyanidin polymer A (having a degree of polymerization of 2 to 11 flavonoid units and an average of about 7) against influenza virus A virus.
Moreover, there exists an influenza virus infection prevention agent which uses tea polyphenol as an active ingredient (refer patent document 2). In this document, tea catechins such as epigallocatechin gallate are listed as tea polyphenols.

Japanese Patent No. 3448052 JP-A-3-101623

The proanthocyanidin polymer described in Patent Document 1 described above is effective for the treatment of respiratory viral infections. However, since the raw material is a croton-type tree that grows in a specific environment such as Amazon, simple and mass production is possible. It was inappropriate. In recent years, such tree takeout tends to be severely restricted for the purpose of protecting genetic resources. In addition, easy take-off and breeding of tree species outside their original habitat can disrupt the ecosystem.
That is, if it is possible to provide a polyphenol having antiviral activity that is more effective than before using raw materials that are easier and cheaper than croton species, it is expected to be used as industrially valuable. The

As a result of intensive studies on the above problems, the present inventors have found that proanthocyanidin-based polyphenols derived from or contained in hop koji or apple immature fruits have an effect on influenza viruses. Furthermore, it was confirmed that these active substances have a stronger activity than tea catechin, and the present invention has been completed.
The polyphenol here is a general term for compounds having a plurality of phenolic hydroxyl groups in the molecule mainly contained in the plant body, and the “proanthocyanidin-based polyphenol” is an anthocyanidin (which is a red pigment by hydrolysis) Cyanidin, delphinidin or pelargonidin).

That is, the first of the present invention is to provide a virus inactivating agent containing a proanthocyanidin-based polyphenol as an active ingredient for inactivating a virus. The second of the present invention is to provide a virus inactivating agent in which the proanthocyanidin-based polyphenol is a polyphenol obtained from apples, particularly apple immature fruits. According to a third aspect of the present invention, there is provided a virus inactivating agent, wherein the proanthocyanidin-based polyphenol is a polyphenol obtained from hops, particularly hop koji.
Here, in the virus inactivating agent of the present invention, the proanthocyanidin-based polyphenol is preferably contained in an amount of 5 to 95% by weight, more preferably 20 to 95% by weight. In particular, when the proanthocyanidin-based polyphenol is a polyphenol obtained from an apple (derived from or contained in an apple), the virus inactivating agent is preferably 20 to 80% by weight, more preferably 50 to 70% by weight. Containing. When the proanthocyanidin-based polyphenol is a polyphenol obtained from hops (derived from or contained in hops), the virus inactivating agent is preferably 20 to 70% by weight, more preferably 25 to 55% by weight. Containing.

In the present invention, the proanthocyanidin-based polyphenol is preferably a proanthocyanidin that does not permeate the membrane when treated with an ultrafiltration membrane having a fractional molecular weight of 1,000 or more.
Furthermore, the present invention provides a beverage or food product containing the above-mentioned virus inactivating agent, preferably in a final concentration range of 1 to 10,000 ppm.
In addition, the present invention also provides a therapeutic method in which the drug is administered to a patient in a total daily dose range of 2 mg to 1000 mg as an oral or parenteral drug, together with the drug containing the virus inactivating agent. It is.
The polyphenol provided by the present invention is stronger than the tea catechin described in JP-A-3-101623 in strength of virus growth inhibitory activity, and is applied to beverages and foods. It is also excellent in taste.

  Since the virus inactivating agent of the present invention has anti-influenza virus activity, it is effective against influenza virus. Moreover, since the component which inactivates influenza virus is a polyphenol derived from or containing hops, particularly hop koji, or apples, particularly apple immature fruits, there is an advantage that raw materials can be easily obtained.

It is the figure which evaluated the degree of proliferation of Sindbis virus in Example 10 by the survival rate of Vero cells. The higher the value on the vertical axis, the more cells survive. It is the figure which evaluated the degree of proliferation of influenza virus in Example 11 by the hemagglutination activity of chorioallantoic fluid. The vertical axis represents the maximum dilution factor showing hemagglutination activity, and the higher this value, the more influenza virus is growing. It is the figure which evaluated the hemagglutination activity of the chicken which the influenza virus in Example 12 has. The vertical axis is a score of the degree of erythrocyte aggregation, and the higher this value, the stronger the infectivity.

The unripe apple fruit used as the raw material of the present invention refers to a fruit that has been artificially picked before the fruit of the apple has matured, or that has fallen from the apple fruit tree naturally by dropping or the like.
Moreover, the hop koji used as the raw material of the present invention is obtained by removing the lupulin portion from the hop koji, and in general, the hop koji is obtained by pulverizing the hop koji and then removing the lupulin portion by sieving. However, in recent beer brewing, in order to save the trouble of sieving and removing hop koji, the hop koji is formed into pellets without removing hop koji that is not useful for beer brewing, and then brewed as hop pellets. It tends to be used. Therefore, the raw material of the present invention is not particularly limited as long as it contains hop straw, and there is no problem even if hop fruit and hop pellets containing hop straw are used as the raw material.

These raw materials are extracted by squeezing with a juice or an aqueous alcohol solution. The extracted liquid is an extract containing a virus inactivating component. If necessary, the virus inactivating component can be purified using a column packed with a granular resin having affinity for polyphenol, etc., and the degree of purification can be increased. However, this process is merely a process for increasing the purity of the virus inactivating agent, and can be omitted if not necessary.
The process of purifying a virus inactivating component using a column (hereinafter referred to as “column”) filled with a granular resin having affinity for polyphenol (hereinafter referred to as “resin”) is performed by using an extract containing the virus inactivating component. After passing through the column and thoroughly washing the column, the virus inactivating agent adsorbed on the column may be eluted, or the granular resin is immersed in an extract containing the virus inactivating component, and batch It can also be processed.

When adsorbing the virus inactivating agent on the resin, if necessary, the extract containing the virus inactivating component is cooled to about 5 to 30 ° C. and extracted in advance by vacuum concentration or the like, if necessary. It is desirable to reduce the organic solvent concentration of the liquid. As the resin material, hydroxypropylated dextran, hydrophilic vinyl polymer, styrene-divinylbenzene polymer, or the like can be used.
The resin can then be washed to increase the purity of the virus inactivating agent. As a solvent used for washing, water or an aqueous ethanol solution of 1 to 10 w / w% (weight / weight%) is preferable, and it is desirable to wash using a solvent amount of about 1 to 10 times the amount of resin.

Subsequently, the virus inactivating agent is desorbed and eluted from the resin adsorbed with polyphenols. As the solvent used for elution, water-containing alcohol, water-containing acetone, water-containing acetonitrile, or the like can be used, and particularly preferable examples include an ethanol aqueous solution or ethanol of 10 w / w% or more. The flow rate of the elution solvent is preferably about 2 to 6 times the resin amount.
The virus inactivating agent can be obtained as a powder by removing the solvent from the obtained eluate by conventional methods such as concentration, freeze drying, spray drying and the like. Further, alcohol, acetone, acetonitrile and the like can be recovered and reused during concentration under reduced pressure. The used synthetic resin can be repeatedly used after being washed with an alcohol aqueous solution of 80 v / v% (volume / volume%) or more, a sodium hydroxide aqueous solution of about 0.05 N, and the like.
The virus inactivating agent thus obtained can be put to practical use as it is, but the degree of purification can be further increased by a method using an ultrafiltration membrane as described below. However, this process is merely a process for increasing the purity of the virus inactivating agent, and can be omitted if not necessary.

In the step of purifying the virus inactivating component using an ultrafiltration membrane, the solution containing the virus inactivating agent obtained by the above method is treated with an ultrafiltration membrane having a fractional molecular weight of 1,000 or more. The solution is preferably water or a solution of an organic solvent miscible with water. A preferred example is an aqueous ethanol solution of 5 to 50%. As a material of the membrane, any material that is usually used as a material for an ultrafiltration membrane such as cellulose, cellulose acetate, polysulfone, polypropylene, polyester, polyethersulfone, PVDF, etc. can be used without particular limitation. In addition, if the molecular weight cut off is 1,000 or more, it can be used without any problem. However, if a membrane having a very high molecular weight cut off is used, the yield is drastically reduced, and if the molecular weight cut off is small, processing is required. Since the time becomes longer, an ultrafiltration membrane having a fractional molecular weight of about 3,000 to 50,000 is preferable. Further, the treatment is preferably carried out until the amount of the remaining liquid becomes about 1/10 to 1/100 at the start of the treatment, although it depends on the kind of the extraction solvent and the ratio of the extraction solvent and hops or hops. The pressure at that time is preferably about 0.1 to 10.0 kg / cm ² , although it depends on the ultrafiltration membrane and the filtration device. If necessary, the remaining liquid once treated can be diluted again with an appropriate solvent such as water and retreated in the same manner to increase the degree of purification.

The virus-inactivating agent can be obtained as a powder by removing the solvent of the obtained residual liquid by a conventional method such as concentration, freeze-drying or spray-drying. Further, alcohol, acetone, acetonitrile and the like can be recovered and reused during concentration under reduced pressure.
The virus inactivating agent thus obtained is an odorless skin-colored, brown or light yellow powder with a faint bitter taste, adsorbed on a synthetic resin having an affinity for polyphenol, and a molecular weight cut-off of 1, Proanthocyanidins that do not permeate the membrane when treated with an ultrafiltration membrane of 000 or more.
When the raw material is hop koji, the yield is 0.5 to 20.0 w / w% in terms of hop koji weight and 0.5 to 15.0 w / w% in terms of hop koji weight. When it is set as an immature apple, it is 0.5-15.0 w / w% in conversion of apple immature fruit weight.

The content (rate) of the active ingredient and proanthocyanidin-based polyphenol in the obtained virus inactivating agent varies depending on the difference in the purification process described above. Depending on the above, a sufficient effect can be expected, and it is not limited at all. More specifically, if the proanthocyanidin-based polyphenol is contained in the virus inactivating agent in an amount of 2% by weight or more, the effect is exhibited as an active ingredient, but in practice, the processing time and labor of the purification process are reduced. Considering this, it is preferable to contain in the range of 5 to 95% by weight, more preferably 20 to 95% by weight.
In particular, when the proanthocyanidin-based polyphenol is a polyphenol obtained from an apple, the virus inactivating agent preferably contains 20 to 80% by weight, more preferably 50 to 70% by weight. When the proanthocyanidin-based polyphenol is a polyphenol obtained from hops, the virus inactivating agent preferably contains 20 to 70% by weight, more preferably 25 to 55% by weight, the polyphenol.

The proanthocyanidin polyphenol content (% by weight) in the virus inactivating agent is generally determined by the method of Porter et al. (Porter et al., Phytochemistry 25, 223-230 ( 1986)) and can be measured relatively easily. This method is a method in which a proanthinidine-based polyphenol-specific interflavan bond is hydrolyzed in the presence of alcohol, and the resulting red pigments such as pelargonidin, cyanidin and delphinidin are quantified at an absorbance of 550 nm. Since various substances exist in proanthocyanidin-based polyphenols, the obtained absorbance is usually converted to the absorbance of proanthocyanidin-based polyphenols having a relatively simple structure, such as procyanidin B1, and expressed as procyanidin B1 content. Can do.
Therefore, the content of proanthocyanidin-based polyphenols in the virus inactivating agent can be determined by using the method of Porter et al.

The thus obtained virus inactivating agent can be formulated with commonly used carriers, auxiliaries, additives, etc., and can be used as a pharmaceutical as an oral or parenteral product according to a conventional method. It can be mixed with foods and drinks.
Pharmaceutical products include tablets, capsules, powders, granules, and syrups as oral preparations, and external preparations such as ointments, creams, and liquids as parenteral preparations, and injections such as sterile solutions and suspensions . It can also be made into mouth preparations such as mouthwash. When these products are treated as drugs by administration to the human body, 2 mg to 500 mg is administered once or several times a day, that is, in a total daily dose of 2 mg to 1000 mg. By executing this treatment method, it is possible to sufficiently inactivate (prevent infection) against viruses such as influenza virus.

The pharmaceutical product containing the virus inactivating agent of the present invention can take the required unit volume form together with physiologically recognized vehicles, carriers, excipients, integrating agents, stabilizers, flavoring agents and the like. The adjuncts mixed in tablets and capsules are as follows. Binders such as tragacanth, gum arabic, corn starch, gelatin, excipients such as microcrystalline cellulose, corn starch, whole gelatinized starch, swelling agents such as alginic acid, lubricants such as magnesium stearate, Sweeteners such as sugar, lactose, saccharin, flavoring agents such as peppermint, red mono oil, and cherry. In the case of capsules, the above-mentioned materials can further contain a liquid carrier such as fats and oils, and other materials can be used as coating agents or the physical form of the preparation can be changed by other methods. it can. For example, tablets can be coated with shellac, sugar. A syrup or elixir may contain sucrose as a sweetening agent, methyl or propylparabens as preservatives, a dye and flavoring such as cherry or orange flavor.
When the pharmaceutical form is an oral preparation such as a tablet, capsule, powder or granule, the content of the virus inactivating agent is preferably in the range of 3 to 50% by weight, more preferably in the range of 5 to 30% by weight. It is.

Sterile compositions for injections dissolve or suspend active substances in vehicles such as water for injection, naturally occurring vegetable oils such as sesame oil, coconut oil, peanut oil, cottonseed oil, or synthetic fat vehicles such as ethyl oleate. It can be formulated by the usual method of turbidity. Moreover, a buffering agent, antiseptic | preservative, antioxidant, etc. can be mix | blended as needed. As an external preparation, vaseline, paraffin, fats and oils, lanolin, macrogol or the like is used as a base material, and an ointment, cream or the like can be obtained by a usual method.
When the pharmaceutical form is an injection, oral preparation, etc., the content of the virus inactivating agent is preferably 0.2 to 10% by weight, more preferably 0.5 to 5% by weight.

Beverages or foodstuffs containing viral inactivating agent of the present invention may be in the form of the formulation, but in addition rain, crackers, cookies, the required amount to each of the product ingredients in the form of such a beverage production general It can also be processed and manufactured by the method. Ingestion as a health food or functional food is used for disease prevention and health maintenance, so it is taken as a processed product containing 5 mg to 500 mg as a total daily dose, divided into several times a day for oral intake.
When the virus inactivating agent is added to these beverages or food products, the virus inactivating agent may be added as a powder, but preferably the virus inactivating agent is added in an aqueous solution or alcohol of 1 to 2% by weight. It is desirable to add an aqueous solution or an alcohol solution so that the final concentration is usually 1 to 10,000 ppm, preferably 100 to 5000 ppm, with respect to the beverage or food product.
Hereinafter, although an Example is shown, this invention is not limited to this.

(Preparation of virus inactivating agent from immature apples)
400 g of apple immature fruit (average weight 5.03 g) was homogenized with 1% hydrochloric acid methanol and extracted with heating under reflux (3 times). The extract was concentrated under reduced pressure to distill off the methanol, and then chloroform was added for distribution. (Twice), the aqueous layer was recovered, filtered, and diluted to 200 ml with distilled water. Furthermore, it was purified by a solid phase extraction method using Sep-pak C18 and freeze-dried to obtain 8.9 g of a virus inactivating agent. The yield from unripe apples was 2.2%.
The virus inactivating agent was measured using size exclusion chromatography (Kurumatani et al., J. Liq. Chromatogr. Realt. Technol. 28, 1971-1983, (2005)). The average molecular weight was calculated to be about 1,500. This corresponds to about a pentamer in terms of catechin.
In addition, when this virus inactivating agent was quantified by proanthocyanidins using the Porter method, it was 63% in terms of procyanidin B1.

(Preparation of virus inactivating agent from hop cake)
50 g of hop koji was extracted with 1,000 ml of 40% ethanol aqueous solution with stirring at 50 ° C. for 60 minutes. After filtration, the solution was concentrated under reduced pressure until the volume reached 500 ml, and the concentrated solution was passed through a column packed with 150 ml of styrene-divinylbenzene resin (Separbeads 70 manufactured by Mitsubishi Chemical Corporation), and then washed with 500 ml of water. Further, 600 ml of 50% ethanol aqueous solution was passed through the same column, and the same eluate was collected and freeze-dried to obtain 1.7 g of a virus inactivating component as a light yellow powder having an odorless faint bitter taste. The yield from hop cake was 3.4%.
Further, proanthocyanidins were quantitatively determined using the Porter method for this virus inactivating agent and found to be 36% in terms of procyanidin B1.

(Further purification of virus inactivating agent using ultrafiltration membrane)
5 g of the virus inactivating component obtained in the same manner as in Example 2 was dissolved in 500 ml of a 20% aqueous ethanol solution and treated with an ultrafiltration membrane (YM10 manufactured by Millipore) having a molecular weight cut-off of 10,000. The remaining liquid that did not pass through this membrane was concentrated and lyophilized to obtain 2.2 g of a further purified virus inactivating agent as a yellow to brown powder. As in Example 1, when measured using size exclusion chromatography, the average molecular weight of the virus inactivating agent was calculated to be about 6,300. This corresponds to approximately 22-mer in terms of catechin.
When this powder was analyzed by HPLC, it became a characteristic chromatogram, and when catechin determination (method described in the official food analysis method), which is one of the general methods for determining polyphenols, was performed, it was converted to catechin content of 40.6. % Values were obtained. (HPLC conditions) Apparatus: Shimadzu LC-10A system, column: ODS-80TM (Tosoh, 4.6 mm ID × 25 cm), mobile phase: (A liquid: B liquid) = (100: 0) to (50:50) Linear gradient for 30 minutes, liquid A: 5% acetonitrile (containing 0.1% HCl), liquid B: acetonitrile, flow rate: 1.0 ml / min, sample injection amount: 20 μg, detection: multi-wavelength detection at 200-300 nm.
The official food analysis method (HPLC method) in the determination of catechin can be measured, for example, according to the method described in the Ministry of Agriculture, Forestry and Fisheries Vegetable and Tea Experiment Station “Analysis Method of Tea” Tea Industry Research Report No. 71 (1990).
This powder (virus inactivating agent) was quantitatively analyzed for proanthocyanidins using the Porter method, and as a result, it was 53% in terms of procyanidin B1.

(Tablets and capsules)
10.0 g of material obtained according to Example 3
Lactose 75.0g
Magnesium stearate 15.0g
Total 100.0g
The above respective parts by weight were uniformly mixed, and tablets and capsules were prepared according to a conventional method. In addition, instead of the substance obtained according to Example 3, tablets and capsules to which the substances obtained according to Examples 1 and 2 were added were obtained in the same manner.

(Powder, granule)
20.0 g of the material obtained according to Example 3
Starch 30.0g
Lactose 50.0g
Total 100.0g
Each said weight part was mixed uniformly, and it was set as the powder and the granule according to the conventional method. In addition, the powder and granule which added the substance obtained according to Example 1, 2, respectively instead of the substance obtained according to Example 3 were obtained similarly.

(Injection)
1.0 g of material obtained according to Example 3
Surfactant 9.0g
Saline 90.0g
Total 100.0g
Each of the above weight parts was mixed by heating and sterilized to obtain an injection. In addition, the powder and granule which added the substance obtained according to Example 1, 2, respectively instead of the substance obtained according to Example 3 were obtained similarly.

(candy)
Sucrose 20.0g
Chickenpox (75% solids) 70.0g
9.5g of water
Coloring material 0.45g
Perfume 0.045g
0.005 g of material obtained according to Example 3
Total 100.0g
Using each component of each of the above parts by weight, it was made into a candy according to a conventional method. In addition, instead of the substance obtained according to Example 3, soot containing the substances obtained according to Examples 1 and 2, respectively, was also obtained.

(juice)
Concentrated tangerine juice 15.0 g
Fructose 5.0g
Citric acid 0.2g
Fragrance 0.1g
0.15 g of color
Sodium ascorbate 0.048g
0.002 g of material obtained according to Example 3
79.5g of water
Total 100.0g
Using each component of the above-mentioned parts by weight, juice was prepared according to a conventional method. In addition, the juice which added the substance obtained according to Example 1, 2 instead of the substance obtained according to Example 3 was obtained similarly.

(cookie)
Soft flour 32.0g
Whole egg 16.0g
16.0g butter
Sand sugar 25.0g
10.8 g of water
Baking powder 0.198g
0.002 g of material obtained according to Example 3
Total 100.0g
Using each component of the above-mentioned parts by weight, a cookie was prepared according to a conventional method. In addition, the cookie which added the substance obtained according to Example 1, 2 instead of the substance obtained according to Example 3 was obtained similarly.

Comparative Example 1
(Taste comparison)
Eleven panelists were allowed to evaluate the taste (astringency) of a 100 ppm aqueous solution of the virus inactivating agent or epigallocatechin gallate (commercial product: Kurita Chemical) obtained in Example 1 or Example 3 by sensory evaluation, Aggregated. The panelists evaluated each aqueous solution with 1-5 points for astringency. (The astringent one was 5 points and the weak one was 1 point.) The results are shown in Table 1. It was confirmed that the virus inactivating agent obtained in Example 1 and Example 3 was superior in taste compared to tea catechin.

  Vero cells obtained by culturing a mixture of each of the virus inactivating agent and epigallocatechin gallate (Kurita Kogyo) obtained in various concentrations of Example 1 and Example 3 and Sindbis virus in a 96-well plate In addition, it was incubated for 1 hour, washed, and cultured at 37 ° C. for 2 days. The concentration of the virus inactivating agent obtained in Example 1 and Example 3 was calculated with molecular weights of 1500 and 6300 from the results of the average molecular weight of size exclusion chromatography. After the culture, the cell viability was evaluated based on the cell activity (Cell Vability) measured with a cell counting kit (manufactured by Doujin Chemical Laboratory Co., Ltd.). As a control, cells not added with polyphenol and virus were used, and the cell activity exhibited by the control was defined as 100%. The result is shown in FIG. The virus inactivating agent obtained in Example 3 showed a stronger virus inactivating effect than epigallocatechin gallate, which is the main component of tea catechin.

  Chorioallantoic cavity of developing chicken eggs obtained by incubating the virus inactivating agent obtained in Example 3 at various concentrations with influenza A virus (influenza A / Beijin / 352/89 (H3N2)) at 4 ° C. for 30 minutes And incubate at 35 ° C. for 48 hours. The concentration of the virus inactivating agent of Example 3 was calculated based on the result of size exclusion chromatography with a molecular weight of 6300. After incubation, chorioallantoic fluid was collected and the amount of influenza virus was evaluated by hemagglutination activity. The result is shown in FIG. The virus inactivating agent of Example 3 suppressed the growth of influenza virus in a concentration-dependent manner.

  Various concentrations of the virus inactivating agent obtained in Example 1 and Example 3 and influenza A virus (influenza A / Beijin / 352/89 (H3N2)) were mixed and incubated at 4 ° C. for 30 minutes. In addition to erythrocytes, the infectivity of the virus was evaluated by its agglutinating activity. The concentration of the virus inactivating agent obtained in Example 1 and Example 3 was calculated with molecular weights of 1500 and 6300 from the results of the average molecular weight of size exclusion chromatography. The result is shown in FIG. The virus inactivating agent obtained in Example 1 and Example 3 inhibited the hemagglutination activity of influenza A virus in a concentration-dependent manner and attenuated the infectivity of the virus.

  Since the virus inactivating agent of the present invention has an effect of suppressing virus growth, it is effective as a medicine, quasi-drug, or beverage or food product having an effect of inhibiting infection of the virus to the host. Can be used.

Claims (11)

  A virus inactivating agent containing a proanthocyanidin-based polyphenol as an active ingredient for inactivating viruses.   The virus inactivating agent according to claim 1, wherein the proanthocyanidin-based polyphenol is a polyphenol obtained from apple.   The virus inactivating agent according to claim 2, wherein the apple is an unripe fruit.   The virus inactivating agent according to claim 1, wherein the proanthocyanidin-based polyphenol is a polyphenol obtained from hops.   The virus inactivating agent according to claim 4, wherein the hop is a hop cocoon.   The virus inactivating agent according to claim 1, comprising 5 to 95% by weight of the proanthocyanidin-based polyphenol.   The virus inactivating agent according to claim 1, wherein the proanthocyanidin-based polyphenol is proanthocyanidin that does not permeate the membrane when treated with an ultrafiltration membrane having a molecular weight cut-off of 1,000 or more.   A beverage product comprising the virus inactivating agent according to any one of claims 1 to 5 in a final concentration range of 1 to 10,000 ppm.   A food product comprising the virus inactivating agent according to any one of claims 1 to 5 in a final concentration range of 1 to 10,000 ppm.   A pharmaceutical comprising the virus inactivating agent according to any one of claims 1 to 5.   The therapeutic method which administers the pharmaceutical of Claim 10 to a patient in the range of 2 mg-1000 mg in a total daily dose as an oral agent or a parenteral agent.

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