JP7470412B2 - Coronavirus killer - Google Patents

Description

The present invention relates to a coronavirus killing agent.

The possible antiviral effects of propolis against influenza viruses and coronaviruses have been reported (e.g., Non-Patent Document 1).

Berretta et al., Biomedicine & Pharmacotherapy, 131, 2020, 110622

However, the virucidal effect of propolis against coronaviruses has not been confirmed so far.

The present invention aims to provide a novel coronavirus killing agent.

The coronavirus killing agent of the present invention contains propolis as an active ingredient.

In the above-mentioned coronavirus killing agent, the target coronavirus may be a porcine coronavirus.

The present invention provides a novel coronavirus killing agent.

The following describes in detail preferred embodiments of the present invention. However, the present invention is not limited to the following embodiments.

The coronavirus killing agent of the present invention contains propolis as an active ingredient. The coronavirus killing agent according to this embodiment contains propolis, and therefore has a coronavirus killing effect.

As used herein, the term "coronavirus killing" refers to killing the coronavirus by directly acting on the coronavirus itself. Specifically, the term "coronavirus killing" may refer to, for example, inactivating or decomposing the target coronavirus.
The term "viricidal" as used herein is different from "antiviral," which is the action of suppressing the proliferation of a virus after it has invaded the body.

The virus reduction rate by the coronavirusicide of this embodiment may be, for example, 90% or more, 95% or more, 98% or more, or 99% or more.

Since the coronavirusicidal agent according to this embodiment has a coronavirusicidal effect, it can also be used, for example, to prevent coronavirus infection and the spread of coronavirus.

The coronavirus that is the target of the coronavirusicidal agent of this embodiment may be, for example, porcine infectious coronavirus (PEDV), human coronavirus (e.g., 229E, NL63, HKU1, OC43), SARS coronavirus, MERS coronavirus, or SARS coronavirus 2.

(Propolis)
Propolis can be obtained, for example, as a beekeeping product according to a conventional method. Propolis may be derived from any plant, such as Alecrin, Eucalyptus, Poplar, Clusia, etc. From the viewpoint of high physiological activity, Alecrin-derived propolis is preferred. Alecrin is Baccharis dura unclifolia, which belongs to the Baccharis genus of the Asteraceae family.

Propolis may be, for example, from Japan, Brazil, China, European countries, Oceania, America, etc. Brazilian propolis is mainly derived from alecrin.

Propolis may be of any rank, such as brown, red, yellow, green, super green, or ultra green, and among these, propolis of the green, super green, or ultra green rank is preferred. These ranks are determined by the amount of artepillin C in the propolis. Propolis containing 3% or more by mass of artepillin C is called green propolis. The amount of artepillin C in the propolis is preferably 5% or more by mass, and more preferably 8% or more by mass.

Propolis is preferably derived from bees belonging to the genus Apis of the family Apidae, and among the genus Apis, it is preferable to use propolis derived from the Western honeybee. There are said to be 24 to 28 subspecies of the Western honeybee, and propolis derived from any subspecies may be used. In particular, it is preferable to use propolis derived from the African honeybee (A. mellifera scutellata), which is a subspecies of the Western honeybee, and the African honeybee, which is a hybrid between another European subspecies of the Western honeybee.

Propolis may be, for example, raw propolis mass, or may be a processed propolis product obtained by subjecting raw propolis mass to some kind of processing. The processed propolis product may be, for example, raw propolis mass that has been subjected to processing such as pulverization, extraction, extract concentration or powderization, powder granulation, or may be the extraction residue remaining after extraction. That is, the processed propolis product may be, for example, a pulverized propolis mass, an extract, a concentrated extract, an extract powder, an extract granule, an extraction residue, or the like. The extraction may be, for example, water extraction, hydrophilic organic solvent extraction, supercritical extraction, or the like. Examples of hydrophilic organic solvents include ethanol, glycerin, and 1,3-butylene glycol. The propolis extract may be obtained by extraction from raw propolis mass, or may be obtained by further extraction from the residue after extraction. The processing method may be one, or two or more may be combined. As the processed propolis product, a hydrophilic organic solvent extract of propolis is preferable because the active ingredients of propolis are extracted efficiently and in a balanced manner in a short time. The processed propolis is preferably a propolis ethanol extract, a propolis water extract, or a propolis hot water extract. The processed propolis may also be a combination of a propolis ethanol extract, a propolis water extract, and a propolis hot water extract.

As propolis, commercially available products may be used. Examples of commercially available products containing propolis include Yamada Bee Farm's Propolis 300, Propolis Liquid 30 (made in Brazil), propolis granules, propolis granules APC, propolis mild, and propolis drink, Morikawa Kenkodo's Neo Propolis Granules, Propolis Granules, Propolis Liquid, Propolis Mild Liquid, Eucalyptus Polis, Labeille's Labeille Propolis (liquid type), Labeille Propolis (capsule type), and Labeille Propolis Honey.

The above-mentioned coronavirus killer can be used at a dose of 1 mg or more, 3 mg or more, 5 mg or more, 10 mg or more, or 20 mg or more per day for an adult weighing 60 kg, as the solid content of propolis, and may also be used at a dose of 1000 mg or less, 800 mg or less, 500 mg or less, 300 mg or less, 100 mg or less, 80 mg or less, or 50 mg or less.

The content of propolis in the coronavirus killing agent is, as a solid content, for example, 0.000000001% by mass or more, 0.00000001% by mass or more, 0.0000001% by mass or more, 0.000001% by mass or more, 0.00001% by mass or more, 0.00001% by mass or more, 0.0001% by mass or more, 0.001% by mass or more, 0.01% by mass or more, 0.1% by mass or more, 1% by mass or more, 3% by mass or more, 3.5% by mass or more, 5% by mass or more relative to the total amount of the agent. , 7% by weight or more, 10% by weight or more, 15% by weight or more, 20% by weight or more, 25% by weight or more, 30% by weight or more, 35% by weight or more, 40% by weight or more, 45% by weight or more, 50% by weight or more, 55% by weight or more, 60% by weight or more, 65% by weight or more, 70% by weight or more, 75% by weight or more, 80% by weight or more, 85% by weight or more, 90% by weight or more, 93% by weight or more, 95% by weight or more, 98% by weight or more, 99% by weight or more, or 100% by weight. The content of propolis in the coronavirus killing agent, as a solid content, based on the total amount of the agent, may be, for example, 100% by mass or less, 99% by mass or less, 98% by mass or less, 95% by mass or less, 93% by mass or less, 90% by mass or less, 85% by mass or less, 80% by mass or less, 75% by mass or less, 70% by mass or less, 65% by mass or less, 60% by mass or less, 55% by mass or less, 50% by mass or less, 45% by mass or less, 40% by mass or less, 35% by mass or less, 30% by mass or less, 25% by mass or less, 20% by mass or less, 15% by mass or less, 10% by mass or less, 8% by mass or less, 5% by mass or less, 3% by mass or less, or 1% by mass or less.

The recipient of the coronavirusicidal agent of this embodiment may be, for example, a healthy individual.

The coronavirus killing agent according to this embodiment may further contain other ingredients in addition to propolis as an active ingredient. Examples of other ingredients include pharma- ceutically acceptable ingredients (e.g., excipients, binders, lubricants, disintegrants, emulsifiers, surfactants, bases, solubilizers, and suspending agents) and food acceptable ingredients (e.g., minerals, vitamins, flavonoids, quinones, polyphenols, amino acids, nucleic acids, essential fatty acids, cooling agents, binders, sweeteners, disintegrants, lubricants, colorants, flavorings, stabilizers, preservatives, sustained-release regulators, surfactants, dissolving agents, and wetting agents).

The coronavirus killing agent according to this embodiment may be in any form, such as a solid, liquid, or paste, and may be in the form of a tablet (including plain tablets, sugar-coated tablets, effervescent tablets, film-coated tablets, chewable tablets, troches, etc.), capsule, pill, powder (dispersed agent), fine granules, granules, liquid, suspension, emulsion, syrup, paste, injection (including the case where it is mixed with distilled water or an infusion such as an amino acid infusion or an electrolyte infusion at the time of use to prepare it as a liquid), etc. These various preparations can be prepared, for example, by mixing propolis with other components as necessary and forming the mixture into the above-mentioned dosage form.

The above-mentioned coronavirus killer can be used as a medicine, quasi-drug, food composition, or cosmetic itself, or as an ingredient in these products. A medicine, quasi-drug, food composition, or cosmetic containing a coronavirus killer as an ingredient can be produced, for example, by adding the above-mentioned coronavirus killer to an intermediate product in the production process of these products.

A medicine, quasi-drug, food composition, or cosmetic comprising the coronavirus killing agent according to this embodiment, or a medicine, quasi-drug, food composition, or cosmetic containing the coronavirus killing agent, may be for killing coronaviruses. These products may be labeled, for example, to inactivate coronaviruses, decompose coronaviruses, destroy coronaviruses, kill coronaviruses, remove coronaviruses, suppress coronaviruses, etc.

The coronavirusicidal agent according to this embodiment may be administered orally or parenterally. The coronavirusicidal agent according to this embodiment may also be an external preparation for skin. The coronavirusicidal agent may be applied directly to the skin site where it is needed, for example, by treatment such as dripping, spraying, or painting. The mode of administration may be oral or parenteral. The coronavirusicidal agent according to this embodiment may be administered once a day, or in multiple divided doses, such as twice or three times a day.

Cosmetics include any cosmetic product that can be applied to the skin, mucous membranes, body hair, head hair, scalp, nails, teeth, facial skin, lips, etc. of animals (including humans).

The formulation of the cosmetic product may be, for example, a solubilized system, an emulsion system, a powder system, an oil liquid system, a gel system, an ointment system, an aerosol system, a water-oil two-layer system, a water-oil-powder three-layer system, etc. The above-mentioned cosmetic product may be, for example, a face wash, a lotion, a milky lotion, a cream, a gel, an essence, a beauty serum, a pack, a mask, a mist, a basic cosmetic product such as a UV protection cosmetic product, a make-up cosmetic product such as a foundation, a lipstick, a blusher, an eye shadow, an eyeliner, a mascara, etc., a face wash, a massage agent, a cleansing agent, an aftershave lotion, a preshave lotion, a shaving cream, a body soap, a soap, a shampoo, a rinse, a hair treatment, a hair styling product, a hair tonic agent, a hair mist, a hair foam, a hair liquid, a hair gel, a hair spray, a hair growth agent, an antiperspirant, a bath agent, a mouth rinse, an oral cosmetic product, a dentifrice, a hand cream, a hand soap, etc.

In addition to propolis as an active ingredient, cosmetics can contain other ingredients commonly used in cosmetics, such as whitening agents, moisturizers, antioxidants, oily ingredients, UV absorbers, surfactants, thickeners, alcohols, powdered ingredients, coloring materials, aqueous ingredients, water, various skin nutrients, etc., as needed.

Examples of formulations for cosmetics containing the coronavirus killer according to this embodiment may include, in addition to the above-mentioned active ingredients, rose damask flower water, honey, royal jelly extract, rosemary leaf extract, yuzu fruit extract, melissa extract, pomegranate extract, eucalyptus extract, olive leaf extract, etc., and may further include ethanol, pentylene glycol, butylene glycol, glycerin, water, etc.

When the coronavirusicide is used as a food composition or as one component of a food composition, it is preferable that the food composition emphasizes the tertiary function of food, i.e., the function of regulating physical condition. Examples of products that emphasize the tertiary function of food include health foods, functional foods, foods with nutritional functions, nutritional supplements, supplements, and foods for specified health uses.

Examples of food compositions include beverages such as soft drinks, such as coffee, juice, and tea drinks, milk drinks, lactic acid bacteria drinks, yogurt drinks, carbonated drinks, and alcoholic beverages, such as sake, Western liquor, fruit wine, and honey wine; spreads, such as custard cream; pastes, such as fruit paste; Western confectioneries, such as chocolate, donuts, pies, cream puffs, gum, jelly, candy, cookies, cakes, and puddings; Japanese confectioneries, such as daifuku, mochi, manju, castella, anmitsu, and yokan; frozen desserts, such as ice cream, popsicles, and sorbet; cooked foods, such as curry, beef bowl, porridge, miso soup, soup, meat sauce, pasta, pickles, and jam; and seasonings, such as dressings, furikake, umami seasonings, and soup bases.

The present invention will be described in more detail below with reference to examples. However, the present invention is not limited to the following examples.

<First liquid: Preparation of propolis ethanol extract>
The ethanol extract of Brazilian green propolis (solid content 55%) was mixed with 10 times the amount of water, and the supernatant water was removed. Then, 95% ethanol was further added to redissolve the propolis, and the solid content of the propolis was adjusted to 0.67%, to prepare the first liquid.

<Preparation of second liquid>
The propolis residue after the ethanol extraction was mixed with 6 times the amount of water and heated at 90°C for 1 hour. It was then frozen at -20°C, thawed, and filtered, and the solid content was adjusted with water to 3.0%, to prepare a second liquid.

<Sample preparation>
The first liquid, the second liquid, and the 1,3-butylene glycol, pentylene glycol, and water were mixed in a mass ratio of 1.8:10:9:3:36.2 to prepare a sample. The solid content of the first liquid was 0.02% and the solid content of the second liquid was 0.5% relative to the total weight of the sample.

<Virucidal test>
0.1 mL of Porcine epidemic diarrhea virus P-5V strain (porcine infectious coronavirus) was added to 1 mL of a 10-fold diluted solution of the above sample, and the sample was sensitized at room temperature (25°C) for 2 hours. The viral genes in the test solution were extracted, and a viral gene test was performed by real-time PCR, and the _Ct (Threshold Cycle) value was calculated. As a result, the _Ct value was 20.6, and the virus reduction rate was estimated to be 98.24%.

As a control experiment, 0.1 mL of Porcine epidemic diarrhea virus P-5V strain (porcine infectious coronavirus) was added to 1 mL of purified water, and after 2 hours, the viral genes in the test solution were extracted and subjected to a viral gene test by real-time PCR to calculate the _Ct (Threshold Cycle) value. As a result, the _Ct value was 15.0, and the virus reduction rate was estimated to be 13.51%.

Claims (2)

A coronavirus killer containing Brazilian green propolis as an active ingredient. The coronavirusicide according to claim 1, wherein the target coronavirus is a porcine coronavirus.