JP3007665B2 - Preventive and therapeutic agent for coronavirus infection and disinfectant - Google Patents

Abstract

PURPOSE:To obtain the title preventive and therapeutic agent containing a specific galenical drug as active ingredient, without requiring labor, free from problem such as the induction of a virulent virus or the remain of a vaccine in animal when the vaccine is administered. CONSTITUTION:The preventive and therapeutic agent containing a galenical drug (especially preferably Caryophylli Flos, Perillae Herba or Rhei Rhizoma) selected from a group consisting of Caryophylli Flos, Schizonepetae Spica, moxa leaf, Perillae Herba, Rhei Rhizoma, Moutan Cortex, Paeoniae Radix, Houttuyniae Herba, Artemisia capillaris Thus b, Lonicerae Flos, Cinnamoni Cortex, Evodiae Fructus, Ginseng Radix, dindera strychnifolia (Sieb at Zucc.) F.Vill and Prunus mume Sieb at Zucc (Japanese apricot) as active ingredients. When said preventive and therapeutic agent is used to an animal, the form is raw galenical drug, cut material thereof, crush-powdered material or powdered grains or an extract of galenical drug active ingredients or the diluent or the concentrated liquid. The dose expressed in terms of dried galenical drug is 0.001-10g/kg of body weight in the case of oral administration and 0.001mg-1g/ kg in the case of parenteral administration, and the administration is preferably carried out over several days to several ten days.

Description

Description: TECHNICAL FIELD The present invention relates to an agent for preventing and treating coronavirus infection in livestock and a disinfectant. In particular, it is a prophylactic and therapeutic agent for coronavirus infection in livestock and a coronavirus disinfectant containing a specific crude drug.

[Conventional technology]

Coronavirus infection in livestock is a disease caused by coronavirus infection, specifically, infectious gastroenteritis (TGE) in swine, coronavirus infection in cattle, coronavirus infection in horses, and coronavirus infection in dogs. Symptoms. Both are severe diseases, characterized by severe diarrhea, highly contagious and, in the case of livestock, significantly reduced productivity.

As a method for preventing and treating such coronavirus infection, conventionally, animals infected with coronavirus infection and animals in contact therewith are promptly isolated and, in the case of livestock, in order to prevent transmission through livestock houses, vessels, feed, etc. In the case of TGE, vaccination has been mainly employed, although the necessary treatment such as disinfection has been adopted, but satisfactory results have not been obtained despite the laboriousness.

[Problems to be solved by the invention]

Therefore, there is a need for elucidation of a prophylactic and therapeutic agent and a disinfectant which have a high preventive and therapeutic effect and a disinfecting effect on such a coronavirus infectious disease and requires little effort.

[Means for solving the problem]

The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, have found that a specific one of a large number of crude drugs is extremely effective for the prevention and treatment and disinfection of such coronavirus infection. Completed the invention.

That is, the present invention relates to the following: Kobo, gold and silver flowers, cinnamon bark, eucalypt, loquat leaves, bamboo boiled, maoh, dajutsu,
Goshu The present invention relates to a preventive and therapeutic agent for coronavirus infectious diseases in livestock, comprising one or more crude drugs selected from the group consisting of ginseng, crow drug and crow plum.

In addition, the present invention provides a sword, a vine, Aiba, soba, rhubarb,
Licorice, Peony, Peony, Jujube, Yin Kobo, gold and silver flowers, cinnamon bark, eucalypt, loquat leaves, bamboo boiled, maoh, dajutsu,
Goshu The present invention relates to a coronavirus disinfectant for livestock breeding sites and breeding equipment, which contains one or more crude drugs selected from the group consisting of ginseng, crow drug and crow plum.

Chou-ji, Tangaku, Aiba, Soyo, Rhubarb, Licorice, Peony, Shakuyaku, Juyaku, Yin Kobo, gold and silver flowers, cinnamon bark, eucalypt, loquat leaves, bamboo boiled, mao, goshu , Ginseng, crow drug and crow plum are all conventionally known as crude drugs for human use, but it has never been shown that such crude drugs are effective in preventing and treating coronavirus infection in livestock. Not known, and thus the present invention is based entirely on unexpected discoveries from the known efficacy of such crude drugs.

Hereinafter, the crude drug used in the present invention will be briefly described.

Clove (Caryophylli Flos): A bud just before flowering, containing eugenol, acetyleugenol, etc.
It is used as an anthelmintic, spice, and cosmetics.

Squizonepetae (Schizonepetae Spica): A spike of scab, containing mentone, limonene, etc. as components and used as an analgesic for humans, an anti-inflammatory drug, and the like.

Artemisiae Folium: It is a leaf of mosaic or mugwort, and contains eucalyptol, sesquiterpene, and the like as components, and is used as a hemostatic, tonic, and blood-supplementing agent for humans.

Perillae Herba: Perillae Herba is a leaf of perillae, containing anthocyan dye, limonene and the like as components, and is used as a human sedative, antitussive and antibacterial agent.

Rhubarb (Rhei Rhizoma): Rhizoma of rhubarb and closely related plants, the outer layer of the rhizome is peeled off or cut vertically, and contains oxyanthraquinone derivatives such as chrysophonic acid, emodin, imodine monoethyl ether, etc. It has been used as a human stomach bitter medicine, laxative, anti-inflammatory drug and the like.

Licorice (Glycyrrhizse Radix): Glycyrrhizse Radix: It is the root of licorice and contains glycyrrhizin and the like as an ingredient, and is used as a human corrigent, an antitussive expectorant and the like.

Peony bark (Moutan Cortex): A root bark of a peony, which contains paeonol, benzoic acid, and the like as components and is used as a human analgesic, antispasmodic, and the like.

Paeoniae Radix: The root of a peony, containing benzoic acid and the like as an ingredient and used as a human analgesic.

Houttuyniae Herba (Houttuyniae Herba): The whole herb of Dokudami, quercitrin,
It contains methyl nonyl ketone, capric acid and the like, and is used as an anti-inflammatory drug for human wounds and urethritis.

Inn Kochin (Artemisiae Capillaris Spic)
a): In Koko is a spikelet of Japanese mugwort and contains capillarin, capraricin, and the like as components, and is used as an anti-inflammatory, antipyretic, and diuretic in humans.

Gold and silver flower (Lonicerae Flos): A bud of honeysuckle, containing luteolin as an ingredient and used as a human blood purification and antidote.

Cinnamoni Cortex (Cinnamoni Cortex): A bark of laurel, containing cinnamaldehyde, cinnamyl acetate, etc. as components, and used as antipyretic, analgesic, stomachic, and intestinal medicine for humans.

Eucommiae Cortex (Eucommiae Cortex): The bark of Eucommiae rubber, containing gutta percha as an ingredient and used as a tonic for humans.

Loquat leaf (Eriobotryae Folium): Loquat leaf, containing urthorn, amygdalin, etc. as components and used as a stomachic for humans.

Chikujo (Phyllostachysis Caulis in Taenia)
m): This is the inner layer of the culm of a bee and contains alundin as a component and is used at the time of human respiratory diseases and the like.

Ephedrae Herba: Ephedrae Herba is an above-ground stem of ephedra which contains ephedrine and the like as an ingredient and is used as an antitussive, sweating and diuretic in humans.

Jujube (Zizyphi Fructus): A fruit of jujube, containing oleanolic acid and the like as an ingredient, and used as a tonic and diuretic for humans.

Goshu (Goshiyu) (Evodiae Fructus): A fruit of Goshuyu, which contains evodiamine and the like as an ingredient and is used as a stomachic for humans.

Ginseng Radix: Ginseng Radix is a root of ginseng, containing ginsenoside and the like as an ingredient and used as a tonic for humans.

Oyaku (Yaku) It is the root of Yaku and contains Linderan as a component and is used as a stomachic and analgesic for humans.

Ume is a smoked plum fruit and contains succinic acid, citric acid, etc. as components, and is used as a refreshing astringent, antidiarrheal, acaricide, and antipyretic for humans.

The preventive and therapeutic agents of the present invention include livestock, that is, pigs,
It can be used as a prophylactic and therapeutic agent for coronavirus infection in domestic animals such as cattle, horses, goats and sheep, and in pet animals such as dogs, cats and rats, especially pigs, cows, horses, sheep,
When used for dogs, cats, etc., it has a great effect on livestock, especially on the pig raising industry and pet industry.

When the crude drug of the present invention is used for prevention of coronavirus infection, it is possible to prevent the infection of livestock to which the crude drug has been administered with coronavirus, and even if the infection occurs, the symptoms are often mild. In addition, when the crude drug of the present invention is used for treatment of livestock infected with coronavirus, the survival rate is improved.

Among the above crude drugs of the present invention, Toji, Soba and Rhubarb are highly effective as agents for preventing and treating coronavirus infection.

In administering the crude drug of the present invention to livestock,
The crude drug substance as it is, in the form of a cut, coarsely pulverized or granular material of the crude drug substance, in the form of an extract obtained by extracting the active ingredient of the crude drug with water or another solvent, or the extract Can be used in diluted or concentrated form. As the concentrated form, a liquid, semi-solid, or solid containing the active ingredient in a concentrated state (extract) by subjecting the extract containing the active ingredient to further concentration or separation means such as concentration, drying, extraction, and precipitation. There are shapes (lumps, powders, granules, molded preparations such as tablets, etc.), and any of them can be used.

When extracting the active ingredient in the crude drug with water or another solvent, the crude drug substance, its coarsely pulverized product or powder is placed in water, another solvent or a mixture thereof, and then immersed, decocted, etc. To extract the active ingredient into a liquid. The liquid temperature and extraction processing time at that time naturally depend on various kinds of requirements such as the type of crude drug, the type and amount of the liquid for extraction, ease of extraction of components, thermal stability, and the presence or absence of volatility. Is about 1 g of liquid for extraction per 1 g of dried crude drug substance
It is preferable to use 1000 ml at a temperature of about 4 to 100 ° C. for about 30 minutes to 10 days. The extraction treatment may be performed in any state of standing, stirring, and shaking.

Examples of other solvents other than water that can be used for extracting the active ingredient include methanol, ethanol, butanol, acetone, ethyl acetate, ether, methylene chloride, chloroform, benzene, carbon tetrachloride, petroleum ether, and the like. .

Among them, the extraction liquid is preferably water, methanol, ethanol or a mixture thereof, and particularly preferably water.

Further, as a method of further concentrating and recovering the active ingredient as an extract from the active ingredient-containing extract prepared as described above, a method of partially or completely removing the solvent of the extract under heating or without heating A method of separating the active ingredient by precipitation with a precipitant, etc., adding another solvent to the active ingredient-containing extract, transferring the active ingredient to the other solvent, concentrating the solution, and removing the other solvent as necessary. A method can be adopted.

Depending on the type of active ingredient contained in the crude drug, the type of extraction solvent used for the extraction of the active ingredient, etc., it is necessary to select the type of the other solvent for concentration, but usually lower aliphatic ethers , Lower halogen alkanes (chloroform,
Dichloroethane, dibromoethane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, etc.), and other petroleum solvents (petroleum ether, petroleum benzene, ligroin, etc.) can be used.

When the solvent used for the extraction and concentration of the active ingredient is a substance whose content is prohibited in veterinary medicine, the prophylactic and therapeutic agent of the present invention does not finally contain the solvent. It is necessary to purify sufficiently.

When administering the prophylactic and therapeutic agents of the present invention to livestock, both oral and parenteral administration can be employed. In the case of oral administration, the crude drug substance, a coarsely pulverized product or powder of the drug substance, an active ingredient-containing extract, a concentrated extract thereof, or the like may be directly fed to livestock or together with feed or drinking water. This is done by paying. In the case of parenteral administration, any of intramuscular administration by injection or application, intraperitoneal administration, subcutaneous administration, nasal administration, intravenous administration and the like can be adopted. For parenteral administration, it is convenient to use it in the form of an extract containing the active ingredient or a concentrate thereof.

The dose is determined by the type of crude drug, the form of the crude drug at the time of administration (for example, whether it is the crude drug substance or an active ingredient extract),
It depends on the type and age of the livestock, the form of administration (whether oral or parenteral) and the symptoms of the disease. In terms of powder, it is usually administered in the range of 0.001 to 10 g / kg of body weight / day for several days to several tens of days, and in the case of parenteral administration, a dried crude drug substance or a crushed product thereof Ordinarily, it is preferably administered in the range of 0.01 mg to 1 g / kg of body weight / day for several days to several tens of days in terms of powder or powder.

Furthermore, the crude drug of the present invention can be used not only for domestic animals but also as a disinfectant, in which case the extract of the crude drug is diluted to a breeding place such as a livestock barn or a container or a tool used for breeding. It is good to spray. As the diluent at that time, it is preferable to use a diluent having a concentration of 0.00001 to 1% w / v in terms of a crude drug substance.

Hereinafter, the present invention will be described specifically with reference to examples, but the present invention is not limited to the examples.

Example 1 Porcine infectious gastroenteritis (TG) was added to 0.05 ml of Dulbecco's modified MEM medium.
E) 0.05 ml of virus-containing solution (2 × 10 ³ PFU / ml solution) (PFU: plaque forming unit) was added, and this solution was inoculated into porcine kidney cells previously cultured in a microplate and incubated at a temperature of 37 ° C. for 1 hour. After sensitization, the mixed solution was removed, 1 ml of Dulbecco's modified MEM medium supplemented with 1.5% CMC was added, and the mixture was cultured at 37 ° C for 5 days. The number of plaques of the TGE virus at that time was counted (Control Example 1).

Separately, the dried crest was placed in distilled water at 5% w / v and slowly heated at a temperature of 100 ° C. for 30 minutes to prepare an extract. The extract was sterilized by filtration through a 0.45 μm filter to prepare 10-fold serial dilutions. To 0.05 ml of each of the 10-fold serial dilutions, 0.05 ml of the same TGE virus-containing solution as used in Control Example 1 was added, sensitized at 37 ° C. for 1 hour, and the solution was pre-cultured on a microplate. Pig kidney cells were inoculated and sensitized at 37 ° C. for 1 hour. The mixture was further removed, and 1 ml of Dulbecco's modified MEM containing 1.5% CMC was added. The mixture was cultured at 37 ° C for 5 days. At that time, the maximum dilution ratio of the diluent in which the number of plaques of the TGE virus was 50% or less of the control example 1 was determined (Example 1).

In place of the end of the letter, instead of the end of the sword, Ikuto, Aiba, Soba, Rhubarb, Licorice, Peony, Shakuyaku, Juyaku, Yin 5% w / for hako, gold and silver flowers, cinnamon bark, tochu and loquat leaves
v, Bamboo-boiled, Mao and crow drug, crow plum each, 2.5% w / v each for a total of 5% w / v. As for ginseng, dilution was performed in the same manner as in Example 1 above, except that the number of plaques of the TGE virus was 50% or less than that of Control Example 1 using powder so that the total would be 5.1% w / v by 1.7% w / v each. The maximum dilution of the solution was determined.

 The above results are shown in Table 1 below.

From the results in Table 1 above, it was found that Toji, Ikuto, Aiba, Sofu, Rhubarb, Licorice, Peony, Shakuyaku, Juyaku, Yin Kobo, gold and silver flowers, cinnamon bark, eucalypt, loquat leaves, bamboo boiled, maoh, dajutsu,
Goshu , Ginseng, crow medicament and crow plum, even when their extracts were diluted 10-fold, the growth of TGE virus was suppressed to 50% or less compared to control example 1 containing no crude drug. It can be understood that it can be done. Furthermore, from the results in Table 1, it can be seen that Toji, Soba and Ootake are the most effective.

Example 2 The T-shaped extract prepared in Example 1 was diluted 100-fold with water and sprayed on a barn. As a result, no cattle coronavirus infection was observed in this barn where the diluted T-shape extract was sprayed, despite the occurrence of diarrhea caused by cattle coronavirus infection in the nearby barn. .

Example 3 A feed containing 0.5% by weight of soybean powder and 0.2% by weight of T-shaped powder was fed to a sow (8 months old) during gestation and continuously after parturition. As a result, TGE
Despite this, piglets born from these piglets fed Soba and clove powder did not show any TGE outbreaks.

〔The invention's effect〕

In the present invention, cloves, thorns, Aiba leaves, So leaves, rhubarb, licorice,
Peony, Shakuyaku, Juyaku, Yin Kobo, gold and silver flowers, cinnamon bark, eucalypt, loquat leaves, bamboo boiled, maoh, dajutsu,
Goshu A vaccination that does not require much labor by providing a preventive and therapeutic agent for coronavirus infection in livestock containing one or more crude drugs selected from the group consisting of ginseng, crow drug and crow plum Can prevent and treat coronavirus infections very effectively without causing problems such as the formation of highly virulent virus and the residual vaccine in livestock animals. The prophylactic and therapeutic agents of the present invention are also useful as coronavirus disinfectants for livestock breeding sites and breeding equipment.

Claims (2)

(57) [Claims] [Claim 1] T-shape, twig, Aiba leaf, soba leaf, rhubarb, licorice, peony bark, peony, jujube, ink Kobo, gold and silver flowers, cinnamon bark, eucalypt, loquat leaves, bamboo boiled, maoh, dajutsu,
Goshu An agent for preventing and treating coronavirus infection in livestock, comprising one or two or more crude drugs selected from the group consisting of ginseng, crow drug and crow plum. (2) T-shape, twigs, Aiba leaves, soybean leaves, rhubarb, licorice, peony, peony, jujube, Kobo, gold and silver flowers, cinnamon bark, eucalypt, loquat leaves, bamboo boiled, maoh, dajutsu,
Goshu A coronavirus disinfectant for livestock breeding sites and breeding tools containing one or more crude drugs selected from the group consisting of ginseng, crow drug and crow plum.