KR20240051744A - Composition for preventing or treating of feline infectious peritonitis comprising Schizonepeta tenuifolia extract as an active ingredient - Google Patents

Abstract

The present invention relates to a composition for the prevention or treatment of feline infectious peritonitis, comprising a feline infectious peritonitis extract as an active ingredient. More specifically, the present invention relates to a composition for the prevention or treatment of feline infectious peritonitis, which contains an extract of the feline coronavirus, which is excellent in the ability to inhibit the growth of feline coronavirus and inhibit cell death caused by feline coronavirus, as an active ingredient. It relates to a veterinary composition, feed additive, health food composition for preventing or treating feline infectious peritonitis, and a method of treating feline infectious peritonitis by administering the same.
The composition of the present invention containing the extract of the cat as an active ingredient has excellent activity in suppressing the expression of feline coronavirus protein and inhibiting cell death caused by feline coronavirus, so it is useful in the prevention or development of treatment for feline infectious peritonitis. It can be.

Description

Composition for preventing or treating feline infectious peritonitis comprising Schizonepeta tenuifolia extract as an active ingredient}

The present invention relates to a composition for the prevention or treatment of feline infectious peritonitis, comprising a feline infectious peritonitis extract as an active ingredient. More specifically, the present invention relates to a composition for the prevention or treatment of feline infectious peritonitis, which contains an extract of the feline coronavirus, which is excellent in the ability to inhibit the growth of feline coronavirus and inhibit cell death caused by feline coronavirus, as an active ingredient. It relates to a veterinary composition, feed additive, health food composition for preventing or treating feline infectious peritonitis, and a method of treating feline infectious peritonitis by administering the same.

Feline infectious peritonitis mainly occurs in young felines before the age of one year, and the incidence rate is about 17%, but the mortality rate is almost 100%, making it the most fatal and difficult to treat cat disease. At the onset, clinical symptoms such as loss of appetite, fever, jaundice, diarrhea, weight loss, neurological symptoms, and uveitis appear, and gradually ascites builds up and difficulty breathing occurs. However, the disease progresses slowly and symptoms appear very slowly, making early detection difficult. it's tough. Additionally, once it develops, it is a very fatal disease with no known appropriate treatment method and a very high mortality rate.

Feline Infectious Peritonitis (FIP) is caused by Feline Infectious Peritonitis Virus (FIPV), a type of coronavirus. FIPV binds strongly to cells and tissues, causing lesions in the collecting ducts of the kidneys and intestinal wall, and causing contamination. It is characterized by being transmitted through food, bedding, urine or feces. Infected individuals are initially asymptomatic for a considerable period of time and act as disease carriers, raising the risk of transmission that can spread the virus for a long period of time.

FIPV is another feline coronavirus (FCoV). Feline enteric coronavirus (FECV) infects and replicates only in enterocytes and causes diarrhea in host cats. After infection in cats, it spontaneously mutates and becomes a macrophage. It is known to be a virus that has been modified to enable infection (Licitra, Beth N et al. "Mutation in spike protein cleavage site and pathogenesis of feline coronavirus." Emerging infectious diseases vol.19,7 (2013): 1066-73). Therefore, FIPV is a virus that is almost similar to FECV, and the formation of FIPV and feline infectious peritonitis can be prevented by eliminating the causative FECV.

Currently, there are no approved vaccines or effective antiviral therapies for the treatment of FIP. Therefore, there is a significant need for the development of compounds to treat FIP in cats, or to treat FIPV or FECV, which cause the disease.

Meanwhile, Schizonepeta tenuifolia is an annual herb of the Lamiaceae family. Its main components are essential oils, including d-menthone, dl-menthone, and a small amount of d-limonene. In addition, heperidine, ursolic acid, luteolin, and daucesterol have been reported (Zhang YH, et al., Zhongguo Zhong Yao Za Zhi., 31(15) , pp1247-57, 2006). Hyeonggae extract has been reported to have antihistamine and antipruritic effects (Tohda C, et al., Biol Pharm Bull., 23(5), pp599-601, 2000), and essential fat, the main ingredient, has antifungal and antifungal effects. It has been reported (Park IK. et al., J Econ Entomol., 99(5), pp1717-21, 2006).

Accordingly, the present inventors tried to search for a substance that can treat feline infectious peritonitis, and as a result, it was confirmed that the extract of the snail is similar to FIPV, inhibits the expression of the FECV protein from which FIPV is derived, and reduces host cell death caused by FECV. The present invention has been completed.

Accordingly, the purpose of the present invention is to provide a veterinary composition, animal feed additive, or health food composition for preventing or treating feline infectious peritonitis (FIP), which contains a cat extract as an active ingredient.

Another object of the present invention is to provide a method for treating feline infectious peritonitis, comprising administering a composition containing a cypress extract as an active ingredient to a mammal other than a human.

Another object of the present invention is to provide an antiviral composition against feline infectious peritonitis virus containing a cat extract as an active ingredient.

In order to achieve the above object, the present invention provides a veterinary composition, animal feed additive, or health food composition for preventing or treating feline infectious peritonitis (FIP), which contains a cat extract as an active ingredient.

In order to achieve another object of the present invention, the present invention provides a method of treating infectious feline peritonitis, comprising administering a composition containing a snail extract as an active ingredient to a mammal other than a human.

In order to achieve another object of the present invention, the present invention provides an antiviral composition against feline infectious mucinitis virus containing an extract of the cat as an active ingredient.

Hereinafter, the present invention will be described in detail.

According to one embodiment of the present invention, it was confirmed that the extract of the cat inhibits the expression of coronavirus proteins, inhibits the proliferation of feline enteric coronavirus (FEPV), and inhibits apoptosis of FECV-infected cells.

Accordingly, the present invention provides a veterinary composition for preventing or treating feline infectious peritonitis, comprising an extract of the cat as an active ingredient.

In the present invention, the "hyeonggae" ( Schizonepeta tenuifolia ) is a flower ear of the Lamiaceae family ( Labiatae ), has the shape of a thin and long barley ear, is about 5 to 10 cm long, and is a purple-greenish-brown plant. It has small lipped flowers and sometimes fruit-bearing calyx tubes, and the entire plant has milky white short hairs. This plant has a unique smell and has the characteristic of giving a slightly cool feeling when put in the mouth. Hyeonggae extract has been reported to have antihistamine and antipruritic effects, and its main ingredient, essential fat, has been reported to have antiparasitic and antifungal effects.

In the present invention, the "mold extract" is preferably extracted using an ultrasonic extraction method. In particular, in the ultrasonic extraction method, the solvent is alcohol having 1 to 6 carbon atoms, acetone, ether, and benzene ( It is preferable to use any one selected from the group consisting of benzene, chloroform, ethyl acetate, methylene chloride, hexane, cyclohexane, and petroleum ether. And most preferably, it is extracted by ultrasonic extraction using ethanol.

The extract of the present invention can be used in liquid form by filtering and/or concentrating, or can be solidified through a conventional drying process such as spray drying or freeze drying. In the drying process, dextrin, etc. may be mixed and dried before spray drying or freeze drying.

As used in the present invention, the term "treatment" or "treating" refers to the application or administration of a therapeutic agent, i.e., this extract (alone or in combination with other veterinary preparations) to a mammal, or the treatment of feline infectious peritonitis, feline infectious disease, etc. Treatment, cure, alleviation, alleviation, alteration, resolution, amelioration, enhancement or treatment of feline infectious peritonitis, feline infectious peritonitis, or treatment of symptoms of peritonitis or in mammals likely to develop feline infectious peritonitis (e.g., diagnostic or disembodied applications). It is defined as the application or administration of a therapeutic agent to a mammal, isolated tissue or cell line with the purpose of affecting the symptoms or likelihood of developing feline infectious peritonitis. Such treatments can be tailored and modified based on knowledge gained, especially from the field of genomic medicine.

As used in the present invention, the term "prevent" or "prevention" means no disorder or disease progression if nothing has occurred, or no further disorder or disease progression if there has already been a disorder or disease progression. Also considered is one's ability to prevent some or all of the symptoms associated with a disorder or disease.

As used in the present invention, the terms “mammal,” “individual,” or “subject” refer to mammals other than humans. For example, mammals other than humans include domestic animals and pets, such as mammals of the sheep, bovine, swine, canine, feline, and rat families. Preferably the mammal, subject or individual may be a cat.

As used herein, the terms “effective amount,” “veterinary effective amount,” and “therapeutically effective amount” refer to a non-toxic sufficient amount of an agent to provide a desired biological result. The result may be a reduction and/or attenuation of the signs, symptoms or cause of the disease, or any other desired change in the biological system. The appropriate treatment amount for any subject can be determined by one of ordinary skill in the art using routine experimentation.

As used herein, the term "composition" or "veterinary composition" refers within the present invention to the mold extract itself or a mixture of the mold extract and a veterinary acceptable carrier. The veterinary composition facilitates administration of the canine extract to a mammal or subject. A variety of techniques exist in the art for administering compounds, including but not limited to intravenous, oral, aerosol, parenteral, ocular, pulmonary, and topical administration.

As used herein, the term "veterinary acceptable" refers to any component of a compound that does not inhibit the biological activity or properties of the compound and is relatively non-toxic, i.e., does not cause undesirable biological effects of the substance or of the composition it contains. It refers to a substance, such as a carrier or diluent, that can be administered to a subject without interacting in a detrimental way with the ingredient.

As used herein, the term "veterinary acceptable carrier" means, within the present invention, a liquid or solid filler involved in transporting or transporting the mold extract to enable it to perform its intended function in or to a mammal; means a veterinary acceptable substance, composition or carrier such as a stabilizer, dispersant, suspending agent, diluent, additive, thickening agent, solvent or encapsulating material. Typically, these components are transported or transported from one organ or part of the body to another organ or part of the body. Each carrier must be “acceptable” in the sense of being compatible with other ingredients of the formula containing the compounds useful within the invention and not causing harm to mammals. Some examples of substances that can serve as veterinary acceptable carriers include: sugars such as lactose, glucose and sucrose used in veterinary formulations; Starches such as corn starch and potato starch; Cellulose and its derivatives such as sodium carboxymethyl cellulose, ethylcellulose and cellulose acetate; tragacanth powder; malt; gelatin; talc; Additives such as cocoa butter and suppository wax; Oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; Glycols such as propylene glycol; polyols such as glycerin, sorbitol, mannitol, and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; Buffering agents such as magnesium hydroxide and aluminum hydroxide; Surfactants; alginic acid; pyrogen removal water; isotonic solution; Ringer's solution; ethyl alcohol; Phosphate buffer solution; and other non-toxic combinable substances. In addition, as used in the present invention, a "veterinary acceptable carrier" is a coating agent, antiviral agent, antibacterial agent, and absorption delaying agent that is capable of combining the activity of the useful compound in the present invention and is physiologically acceptable to mammals in part or in whole. Including my back. Additionally, supplementary active compounds may be incorporated into the composition. Other additional ingredients that may be included in the veterinary compositions used in the practice of the present invention are known in the art and are described, for example, in Remington's Pharmaceutical Sciences, Genaro, Ed., Mack Publishing Co., incorporated herein by reference. , 1985, Easton, PA).

The veterinary composition according to the present invention may further include appropriate excipients and diluents commonly used in the preparation of veterinary compositions.

Excipients and diluents that may be included in the veterinary composition according to the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium. Silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, cetanol, stearyl alcohol, liquid paraffin, sorbitan mono. Examples include stearate, polysorbate 60, methylparaben, propylparaben, and mineral oil.

The veterinary composition according to the present invention may further include fillers, anti-aggregants, lubricants, wetting agents, spices, emulsifiers, preservatives, etc. The veterinary composition according to the present invention provides rapid and sustained release of the active ingredients after administration to animals. or may be formulated using methods well known in the art to provide sustained release, the dosage form being powders, granules, tablets, capsules, suspensions, emulsions, solutions, syrups, aerosols, soft or hard gelatin capsules, It may be in the form of a suppository, sterile injectable solution, or sterile topical medication.

The veterinary composition according to the present invention may vary depending on the age, sex, and weight of the animal, but may be administered in an amount of 0.1 to 100 mg/kg once or several times a day. Additionally, the dosage of Hyeonggae extract may be increased or decreased depending on the route of administration, severity of disease, gender, weight, age, etc. Accordingly, the above dosage does not limit the scope of the present invention in any way.

Furthermore, the veterinary composition of the present invention can be administered in combination with known compounds that have preventive and therapeutic effects on feline infectious peritonitis.

The present invention also provides a food composition for preventing or ameliorating feline infectious peritonitis, comprising an extract of the antler as an active ingredient.

In addition, the present invention provides an animal feed additive useful for preventing and ameliorating feline infectious peritonitis, which contains the extract of the cat as an active ingredient, and a feed containing the same.

The composition for animal feed additives may be a highly concentrated solution of 20 to 90% or may be in the form of powder or granules.

The animal feed additive of the present invention contains organic acids such as citric acid, humalic acid, adipic acid, lactic acid, and malic acid, phosphates such as sodium phosphate, potassium phosphate, acid pyrophosphate, and polyphosphate (polymerized phosphate), polyphenols, catechin, It may additionally contain one or more of natural antioxidants such as alpha-tocopherol, rosemary extract, vitamin C, green tea extract, licorice extract, chitosan, tannic acid, and phytic acid.

The animal feed additive of the present invention and the feed containing it contain various auxiliaries such as amino acids, inorganic salts, vitamins, antibiotics, antibacterial substances, antioxidants, anti-fungal enzymes, live microbial agents, etc. as auxiliary ingredients, such as grains, for example, crushed or crushed. wheat, oats, barley, corn and rice; Vegetable protein feeds, such as those based on rapeseed, soybean and sunflower; Animal protein feeds such as blood meal, meat meal, bone meal and fish meal; After mixing all dry ingredients and dry additives made of sugar and dairy products, such as various powdered milk and whey powder, liquid ingredients and ingredients that become liquid after heating, that is, lipids, such as animal fat optionally liquefied by heating. In addition to the main ingredients such as and vegetable fat, it can be used with substances such as nutritional supplements, digestion and absorption enhancers, growth promoters, and disease prevention agents.

The animal feed additive may be administered to animals alone or in combination with other feed additives in an edible carrier.

In addition, the animal feed additives can be easily administered as a top dressing, by mixing them directly into animal feed, or separately from the feed, in a separate oral formulation, by injection or transderm, or in combination with other ingredients. Typically, single daily doses or divided daily doses may be used, as is well known in the art.

When the animal feed additive is administered separately from animal feed, the dosage form of the extract can be prepared as an immediate-release or sustained-release formulation by combining them with a non-toxic pharmaceutically acceptable edible carrier, as is well known in the art. These edible carriers can be solid or liquid, such as corn starch, lactose, sucrose, soy flakes, peanut oil, olive oil, sesame oil and propylene glycol. If a solid carrier is used, the dosage form of the extract may be tablets, capsules, powders, turmeric or sugar-containing tablets or a top dressing in microdisperse form. If a liquid carrier is used, the dosage form may be a soft gelatin capsule, or a syrup or liquid suspension, emulsion or solution. Additionally, the dosage forms may contain adjuvants such as preservatives, stabilizers, wetting or emulsifying agents, solution accelerators, etc. Additionally, they may contain other substances useful for improving and preventing diseases caused by viruses.

Additionally, the animal feed included as the animal feed additive according to the present invention may be any protein-containing organic grain flour commonly used to meet the dietary needs of animals. These protein-containing flours typically consist primarily of corn, soybean flour, or corn/soybean flour mixes.

The above animal feed additives can be used by adding them to the animal feed by dipping, spraying, or mixing.

In the method of mixing animal feed containing the extract according to the present invention, the animal feed additive is incorporated into the animal feed in an amount of about 1 g to 100 g per 1 kg of feed based on dry weight.

Additionally, after the feed mixture is thoroughly mixed, a lightly viscous granular or granular material is obtained depending on the degree of pulverization of the ingredients. This is supplied as a mash or formed into the desired discrete shape for further processing and packaging. At this time, in order to prevent separation during storage, it is desirable to add water to the animal feed and then subject it to conventional pelleting, expansion, or extrusion processes. Excess water can be removed by drying.

The present invention also provides a mammalian health food composition for preventing or ameliorating feline infectious peritonitis, comprising an extract of the cat as an active ingredient.

The health food composition of the present invention is for mammals and may be a tablet, capsule, pill, powder or liquid, and can be consumed on its own or added to various foods or beverages at a ratio of 0.01 to 100% by weight.

The present invention also provides an antiviral composition against feline infectious peritonitis virus containing an extract of the cat as an active ingredient.

The antiviral composition according to the present invention may be a quasi-drug composition.

The quasi-drug composition of the present invention is not limited thereto, but is preferably used as a disinfectant cleaner, shower foam, gargle, wet tissue, detergent soap, hand wash, humidifier filler, toilet pad, disinfectant spray, mask, ointment, patch, or filter filler. It can be used for the purpose of removing and disinfecting the feline infectious peritonitis virus, preventing mammals from being infected with the feline infectious peritonitis virus, and for the purpose of topology.

The composition of the present invention, which contains the extract of the cat as an active ingredient, has an excellent ability to inhibit the proliferation of FECV and cell death caused by FECV by inhibiting the protein expression of FECV, which is derived from FIPV, and is therefore useful for the prevention or development of a treatment for feline infectious peritonitis. It can be utilized effectively.

Figure 1 shows that the expression of feline coronavirus (FECV) protein is suppressed by extract of Hyeonggae.
Figure 2 shows that cell death caused by feline coronavirus (FECV) is inhibited by Hyeonggae extract.

Hereinafter, the present invention will be described in detail. However, the following examples only illustrate the present invention, and the content of the present invention is not limited to the following examples.

Example 1. Preparation of mold extract

To prepare Hyeonggae extract, Hyeonggae flower spikes were purchased from Seohyeon Herbal Medicine Farming Association. After drying the flower spikes, they were made into powder, 40 ml of ethanol was added to 4 g of the flower spikes, and extracted using an ultrasonic extraction method twice for 3 hours at 40°C. The extracted filtrate was evaporated to dryness to obtain 190.8 mg of ethanol extract.

Example 2. Confirmation of the coronavirus proliferation inhibition effect of Hyeonggae extract

After infecting the cat cell line CRFK with feline coronavirus (FECV), the feline extract prepared in Example 1 was treated at concentrations of 2.5, 5, 10, and 20 μg/ml, respectively, and after 72 hours, the cells and Cell culture fluid was obtained and the expression of viral proteins was confirmed through Western blot.

As a result, as can be seen in Figure 1, it was confirmed that the expression of coronavirus protein was significantly reduced in a concentration-dependent manner when the cells were treated with the extract of Hyeonggae compared to the untreated control group.

Example 3. Confirmation of the effect of Hyeonggae extract on inhibiting cell death caused by coronavirus

After infecting the feline cell line CRFK with feline coronavirus (FECV), the feline extract prepared in Example 1 was treated at concentrations of 2.5, 5, 10, and 20 μg/ml, respectively, and cell viability after 72 hours was calculated using the MTT method.

As a result, as can be seen in Figure 2, when nothing was treated, cell viability decreased by more than 40% due to coronavirus infection, but in the group treated with Hyeonggae extract, cell viability increased in a concentration-dependent manner. Confirmed. From this, it was confirmed that Hyeonggae extract inhibits cell death caused by coronavirus.

The composition of the present invention containing the extract of the cat as an active ingredient has excellent activity in suppressing the expression of feline coronavirus protein and inhibiting cell death caused by feline coronavirus, so it is useful in the prevention or development of treatment for feline infectious peritonitis. It has high industrial applicability.

Claims (13)

A veterinary composition for the prevention or treatment of feline infectious peritonitis (FIP), containing extract of the cat as an active ingredient.
The veterinary composition according to claim 1, wherein the veterinary subject is a cat.
The veterinary composition of claim 1, wherein the veterinary composition is for oral, intravenous, intraperitoneal, intramuscular or subcutaneous administration.
An animal feed additive for the prevention or treatment of feline infectious peritonitis containing extract of the snail as an active ingredient.
Animal feed, characterized in that it contains the animal feed additive according to paragraph 4.
The food according to claim 5, wherein the food is for cats.
A mammalian health food composition for preventing or improving feline infectious peritonitis, comprising extract of the snail as an active ingredient.
The health food composition according to claim 7, wherein the mammal is a cat.
A method of treating feline infectious peritonitis, comprising the step of administering a composition containing a cat extract as an active ingredient to a mammal other than a human.
The method of claim 9, wherein the mammal is a cat.
An antiviral composition against feline infectious peritonitis virus comprising extract of the cat as an active ingredient.
The antiviral composition according to claim 11, wherein the antiviral composition is a quasi-drug composition.
The antiviral composition according to claim 12, wherein the quasi-drug is selected from the group consisting of disinfectant cleaners, shower foams, wet tissues, detergent soaps, humidifier fillers, toilet pads, and disinfectant sprays.