Anticoccidial composition containing stilbene compounds and use thereof

Abstract

The present application relates to an anticoccidial composition comprising a stilbene compound and its use. According to one embodiment, the composition comprising the compound or its salt has the excellent effect of directly killing protozoa that can induce coccidiosis, inhibiting the cell invasion of the protozoa, and / or inhibiting the proliferation of the protozoa in cells, and has excellent effects on preventing, alleviating, and treating coccidiosis in vivo.

Description

Technical Field

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of priority based on Korean Patent Application No. 10-2020-0125242, filed on September 25, 2020, and all contents disclosed in the corresponding Korean patent application document are incorporated as a part of this specification.

[0003] The present application relates to an anticoccidial composition comprising a stilbene compound and uses thereof. Background Art

[0004] Coccidiosis is an intestinal disease caused by a protozoan parasite called Eimeria belonging to the phylum apicomplexan, and when infected with coccidiosis, symptoms such as digestive system disorders, diarrhea, and weight loss appear, and in addition, the disease can lead to the death of livestock. Therefore, coccidiosis has a significant economic impact on farms around the world (Williams RB. A compartmentalized model for the estimation of the cost of coccidiosis to the world's chicken production industry, Int J Parasitol, 1999; 29(8): 1209-1229).

[0005] Over the past few years, many researchers have developed anticoccidial agents as therapeutic agents for coccidiosis. These agents, such as ionophores or chemically synthesized compounds, can inhibit the formation of the oocyst cell wall and the asexual and sexual reproduction of protozoa. However, the long-term use of a shuttle program that alternates between ionophores and chemically synthesized compounds has led to side effects such as the emergence of drug-resistant protozoa.

[0006] In particular, the accumulation of antibiotics in animals due to misuse and abuse is a serious problem, as humans consume antibiotics through meat. Consequently, many countries around the world are banning the use of antibiotics due to the problem of antibiotic residues in livestock products. Therefore, there is an urgent need to develop and research alternatives to conventional coccidiostats, which exhibit side effects such as the emergence of drug-resistant strains and internal residues.

[0007] Therefore, the inventors of the present application have completed the present invention by confirming that stilbene compounds have excellent anticoccidial activity and antiprotozoal activity against protozoa that manifest coccidiosis.

[0008] Existing technology

[0009] Patent Literature

[0010] (Patent Document 1) U.S. Patent Publication No. 2008-0160000 Summary of the Invention

[0011] Technical issues

[0012] One embodiment of the present application provides a pharmaceutical composition for preventing or alleviating coccidiosis, comprising a compound of the following Chemical Formula 1 or a salt thereof as an active ingredient.

[0013] Another embodiment of the present application provides a pharmaceutical composition for preventing or treating coccidiosis, comprising a compound of the following Chemical Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0014] Another embodiment of the present invention provides an antiprotozoal composition for use against Eimeria sp. protozoa, comprising the compound of the following Chemical Formula 1 or a salt thereof as an active ingredient.

[0015] Other embodiments of the present application provide a method for preventing, alleviating or treating coccidiosis, comprising the step of administering the composition to an animal other than a human.

[0016] Other embodiments of the present application provide a use of a compound of the following Chemical Formula 1 or a salt thereof for preventing, alleviating or treating coccidiosis.

[0017] Other embodiments of the present application provide a use of a compound of the following Chemical Formula 1 or a salt thereof in preparing a pharmaceutical composition for preventing or alleviating coccidiosis.

[0018] Other embodiments of the present application provide a use of a compound of the following Chemical Formula 1 or a salt thereof in preparing a pharmaceutical composition for preventing or treating coccidiosis.

[0019] Other embodiments of the present application provide the use of a compound of the following Chemical Formula 1 or a salt thereof in preparing a composition (e.g., a pharmaceutical composition) for preventing, alleviating and / or treating coccidiosis or preparing an antiprotozoal composition; the use of a compound of the following Chemical Formula 1 or a salt thereof for preventing, alleviating and / or treating coccidiosis; and / or the use of a compound of the following Chemical Formula 1 or a salt thereof for antiprotozoal treatment of Eimeria protozoa (e.g., killing Eimeria protozoa; and / or inhibiting cell invasion and / or proliferation of Eimeria protozoa).

[0020] Technical Solution

[0021] The present application relates to a technology for providing a stilbene compound as an active ingredient that has the activity of preventing, alleviating or treating coccidiosis. In one embodiment, the stilbene compound can be a compound of the following Chemical Formula 1.

[0022] In one aspect, a pharmaceutical composition for preventing or alleviating coccidiosis may be provided, comprising a compound of the following Chemical Formula 1 or a salt thereof.

[0023] [Chemical Formula 1]

[0024]

[0025] In Chemical Formula 1,

[0026] R1 and R2 may each independently be OH or OCH3.

[0027] In one embodiment, R1 and R2 may each be OCH3.

[0028] In another embodiment, R1 and R2 can each be OH.

[0029] In another embodiment, R1 may be OH and R2 may be OCH3.

[0030] In one embodiment, the compound of Chemical Formula 1 may be a compound selected from the group consisting of:

[0031] 1) 3,5-dimethoxy-4'-hydroxystilbene;

[0032] 2) 3,4,5-trihydroxystilbene, and

[0033] 3) 3-Methoxy-4',5-dihydroxy-trans-stilbene.

[0034] 3,5-Dimethoxy-4'-hydroxystilbene has the chemical formula C 16 H 16 O3, which may be named pterostilbene, is a compound having a structure of the following Chemical Formula 2, and may be CAS No. 537-42-8.

[0035] [Chemical Formula 2]

[0036]

[0037] 3,4,5-Trihydroxystilbene has the chemical formula C 14 H 12 O3, which may be named resveratrol, is a compound having a structure of the following Chemical Formula 3, and may be CAS No. 503-36-0.

[0038] [Chemical Formula 3]

[0039]

[0040] 3-Methoxy-4',5-dihydroxy-trans-stilbene has the chemical formula C 15 H 14 O3, which may be named pinostilbene, is a compound having a structure of the following Chemical Formula 4, and may be CAS No. 42438-89-1.

[0041] [Chemical Formula 4]

[0042]

[0043] The compound of Chemical Formula 1 or a salt thereof can be purchased as a commercial product, or can be obtained by extraction and separation from natural products or strains and prepared by a common organic synthesis method, but is not limited thereto.

[0044] For example, it can be directly isolated from species belonging to the genus Escherichia, Saccharomyces, or Corynebacterium, or obtained from manufacturers in the art, but is not limited thereto.

[0045] Therefore, the inventors of the present application have confirmed that the stilbene compounds exhibit anticoccidial activity against protozoa and have excellent antiprotozoal activity against coccidiosis, thereby completing the present invention.

[0046] In the present application, the "salt of the compound of Chemical Formula 1" may refer to a physiologically acceptable salt in a salt of a substance in which a cation and an anion are bound by electrostatic attraction, for example, a salt acceptable to a feed composition, a pharmaceutically acceptable salt and / or an antiprotozoal composition. For example, the salt may be at least one selected from the group consisting of a metal salt, a salt with an organic base, a salt with an inorganic acid, a salt with an organic acid, a salt with a basic or acidic amino acid, and the like. In one embodiment, the metal salt may be at least one selected from the group consisting of an alkali metal salt (sodium salt, potassium salt, etc.), an alkaline earth metal salt (calcium salt, magnesium salt, barium salt, etc.), an aluminum salt, and the like; the salt with an organic base may be at least one selected from the group consisting of a salt with triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine, N,N-dibenzylethylenediamine, and the like; the salt with an inorganic acid may be at least one selected from the group consisting of a salt with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, and the like. The salt with an organic acid may be at least one selected from the group consisting of salts with formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, etc.; the salt with a basic amino acid may be at least one selected from the group consisting of salts with arginine, lysine, ornithine, etc.; and the salt with an acidic amino acid may be at least one selected from the group consisting of salts with aspartic acid, glutamic acid, etc.

[0047] In the present application, excellent anticoccidial efficacy (activity, effect) may refer to at least one (e.g., any one, two or more, three or more, or all) selected from the group consisting of the following (1) to (5):

[0048] (1) a higher anticoccidial index (ACI) compared with the control group;

[0049] (2) when administered to coccidiosis-induced animal subjects, reduced mortality, reduced lesion scores (e.g., appendiceal lesion scores), and / or reduced fecal oocyst excretion compared to a control group;

[0050] (3) inhibiting weight loss by inducing coccidiosis;

[0051] (4) higher insecticidal activity against coccidiosis-inducing protozoa compared to the control group; and

[0052] (5) The inhibitory effect on cell invasion of protozoa that induce coccidiosis is higher than that of the control group, and / or the inhibitory effect on the proliferation of the protozoa in cells is higher.

[0053] In the present application, the control group may refer to a negative control group (a group without any treatment or a group treated with water and / or buffer) and / or a positive control group comprising conventionally known anticoccidial agents (e.g., diclazuril, salinomycin and / or gallic acid).

[0054] The composition according to one embodiment may have at least one characteristic (e.g., one or more, two or more, three or more, four or more, five or more, or all six) selected from the group consisting of the following (1) to (6), and the characteristics thereof may be superior to those of the control group:

[0055] (1) Excellent anticoccidial activity;

[0056] (2) Excellent antiprotozoal effect against protozoa that cause coccidiosis;

[0057] (3) Excellent acid resistance;

[0058] (4) Excellent heat resistance;

[0059] (5) excellent in vivo stability and / or safety; and

[0060] (6) Excellent effect on improving weight gain.

[0061] The composition according to one embodiment has excellent acid resistance and / or heat resistance, thereby maintaining excellent anticoccidial activity for a long time when administered to the body, and has in vivo stability, thereby maintaining excellent anticoccidial activity even in environments of various temperatures and / or various pH ranges, and can be applied to various products, and storage stability can be excellent.

[0062] According to one embodiment, when administered in vivo, the composition is not absorbed by other tissues and organs (e.g., blood, liver, kidneys, and / or spleen, etc.) except the intestine, thereby having low residues in the body, and thus the composition can have excellent safety in the body.

[0063] In one embodiment, the excellent effect of improving weight gain may refer to an excellent effect of increasing the weight of a subject when administered to a subject in whom coccidiosis is induced, and in one embodiment, the weight gain may refer to daily weight gain.

[0064] The composition according to one embodiment exhibits anticoccidial activity equivalent to or higher than that of conventionally known anticoccidial agents (e.g., sulfonamides such as sulfaquinoxaline, sulfachloropyrazine, and sulfamethazine, polyether ionophore antibiotics such as salinomycin and monensin sodium, amprolium, diclazuril, gallic acid, and / or toltrazuril), but the composition does not cause side effects or drug resistance, and thus can be safe for long-term use.

[0065] In the present application, "prevention" refers to all actions that inhibit or delay the development of a disease by administering a composition according to one embodiment, "treatment" refers to all actions that alleviate or beneficially change the symptoms of a subject suspected of having developed the disease by administering a composition according to one embodiment, and "relief" refers to all actions that reduce parameters associated with the condition of the disease being treated, for example, at least the degree of symptoms, by administering a composition according to one embodiment. The disease may refer to coccidiosis.

[0066] In the present application, "coccidiosis" is a disease in which coccidia protozoa (protozoa that can induce coccidiosis, such as Eimeria sp. coccidia protozoa) parasitize in the cytoplasm of the submucosal tissue in the epithelium of the digestive tract and destroy the epithelium to cause enteritis, and is a protozoan disease that causes economic losses due to weight gain degradation caused by soft stools, diarrhea and bloody stools and prolongs the age of slaughter in broiler farms. Coccidiosis can occur not only in broilers, but also in birds and mammals. Specifically, coccidiosis can infect cattle, rabbits, goats, dogs, cats, mice and rats that are experimental animals, etc., and in particular, it can cause fatal damage to poultry such as chickens. In one embodiment, coccidiosis can include acute coccidiosis, subacute coccidiosis and chronic coccidiosis, etc. Acute coccidiosis can manifest as bloody stools, energy loss, and anemia within 48 hours of infection, and infected subjects may die. Subacute coccidiosis can manifest as bloody diarrhea and / or anemia symptoms after infection. Chronic coccidiosis can manifest as soft stools and / or weight loss after diarrhea within 1 to 2 days after infection.

[0067] When the oocyst (cyst, egg) of coccidia protozoan species matures into oocyst with sporulation under high humidity and high temperature, the oocyst has infectivity, and when the oocyst is discharged with feces after a certain life cycle in the body of the experimenter, the oocyst is easy to spread and the life cycle of the oocyst is constantly repeated. The oocyst (cyst) of known coccidia protozoan species is very high in resistance to the external environment, and the cyst wall is composed of two layers, an inner layer and an outer layer. The outer layer of the cyst wall is a gelatin material, which strongly resists external physical pressure, and the inner layer is rich in nucleoprotein, so it can strongly resist chemical stimulation, such as disinfectants. The oocyst of coccidia protozoan species can include 4 sporangia, and each sporangia can include 2 sporozoites. After they infect animals with the oocyst form, they are released with the form of sporocysts and sporozoites, proliferate in the cell, and the sporozoites through sexual reproduction and / or asexual reproduction can form oocysts and are extracted in feces. In one embodiment, the sporozoite may be used in the same sense as a protozoa, and sporozoites (protozoa) may cause pathology.

[0068] According to one embodiment, the coccidiosis may be caused by a protozoan of the genus Eimeria. In one embodiment, the protozoan of the genus Eimeria may be at least one selected from the group consisting of: Eimeria acervulina, Eimeria tenella, Eimeria maxima, Eimeria necatrix, Eimeria brunetti, Eimeria hagani, Eimeria mitis, Eimeria praecox, Eimeria mivati, Eimeria aurati, Eimeria baueri, Eimeria lepidosirenis, Eimeria leucotti, Eimeria truncatum ... leucisci), Eimeria rutile, Eimeria vanasi, Eimeria amphisbaeniarum, Eimeria witchery, Eimeria yemenensae, Eimeria adenoeides, Eimeria colchici, Eimeria curvata, Eimeria dispersa, Eimeria duodenalis, Eimeria fraterculae, Eimeria gallopavonis, Eimeria innocua, Eimeria meleagridis, Eimeria turkey mild meleagrimitis), Eimeria phasiani, Eimeria procera, Eimeria purpureicephali, Eimeria ahsata, Eimeria alabamensis, Eimeria ariyewialijevi), Eimeria aspheronica, Eimeria arloingi, Eimeria arundelii, Eimeria bakuensis, Eimeria bovis, Eimeria cameli, Eimeria caprina, Eimeria caprovina, Eimeria christenseni, Eimeria clethrionomyis, Eimeria coecicola, Eimeria contorta, Eimeria couesii, Eimeria crandallis, Eimeria damar dammahensis), Eimeria dowleri, Eimeria exigua, Eimeria falciformis, Eimeria farasanii, Eimeria ferrisi, Eimeria flavescens, Eimeria gallatii, Eimeria granulosa, Eimeria hirci, Eimeria intestinalis, Eimeria irresidua, Eimeria intricata, Eimeria jolchijevi, Eimeria krijgsmanni, Eimeria Larrimersoni, larimerensis), Eimeria macusaniensis, Eimeria magna, Eimeria marconii, Eimeria media, Eimeria melanuri, Eimeria missimyoxi), Eimeria nagpurensis, Eimeria nieschulzi, Eimeria ninakohlyakimovae, Eimeria ovinoidalis, Eimeria pallida, Eimeria palustris, Eimeria papillata, Eimeria perforans, Eimeria phocae, Eimeria pileata, Eimeria pipistrellus, Eimeria piriformis, Eimeria prionotemni, Eimeria procyoni, procyonis), Eimeria punctate, Eimeria roobroucki, Eimeria saudiensis, Eimeria sealanderi, Eimeria separateta, Eimeria stiedae, Eimeria ursini, Eimeria vermiformis, Eimeria weybridgensis, Eimeria wobati, and Eimeria zuernii.

[0069] The composition according to one embodiment can have an excellent effect of preventing, alleviating and / or treating coccidiosis caused by at least one protozoa selected from the group consisting of the Eimeria protozoa described in Table 1 below. The Eimeria protozoa described in Table 1 below can cause coccidiosis in the animals described in Table 1, respectively.

[0070] Table 1

[0071]

[0072]

[0073]

[0074]

[0075] The composition according to one embodiment may have excellent effects on preventing, alleviating and / or treating coccidiosis caused by Eimeria tenella, Eimeria acervulina and / or Eimeria maxima.

[0076] In one embodiment, the prevention or alleviation of coccidiosis may refer to at least one (e.g., any one, two or more, three or more, or all) selected from the group consisting of the following (1) to (4), and for example, compared to a control group (a negative control group and / or a positive control group), at least one selected from the group consisting of the following (1) to (4) may be reduced, inhibited, and / or increased:

[0077] (1) reducing at least one of the following: lesion score (e.g., appendectomy lesion score), fecal oocyst excretion, and mortality;

[0078] (2) Inhibit weight loss caused by coccidiosis;

[0079] (3) increase the anticoccidial index (ACI); and

[0080] (4) Reducing cell invasion by Eimeria protozoa, proliferation of protozoa in cells, or both.

[0081] In one embodiment, the lesion scoring method for determining the lesion score can be performed with reference to the literature of Johnson JK and Reid WM (1970) (Joyce Johnson and W. Malcolm Reid, Anticoccidial drugs: Lesion scoring techniques in battery and floor-pen experiments with chickens, Experimental parasitology, 1970), and the lesion score can be 0 to 4. In one embodiment, the lesion score can refer to the lesion score measured in the appendix, duodenum and / or jejunum, and can be calculated by summing the scores of each lesion measured in each organ (appendix, duodenum and / or jejunum).

[0082] In one embodiment, the amount of fecal oocysts extracted can be measured by collecting feces excreted by a subject and using a microscope or a counting chamber (eg, a McMaster chamber).

[0083] In one embodiment, the mortality rate may refer to the mortality rate of animal subjects in which coccidiosis is induced, and the number of subjects whose deaths can be excluded from causes other than coccidiosis by performing an autopsy.

[0084] In one embodiment, the weight of a subject in which coccidiosis is induced may be reduced compared to a subject in which coccidiosis is not induced. The composition according to one embodiment can inhibit the weight loss caused by inducing coccidiosis.

[0085] In one embodiment, the anticoccidial index can be calculated according to the following equation 1, and in equation 1, the lesion score can be calculated according to the aforementioned method.

[0086] (Equation 1)

[0087] Anticoccidial index (ACI) = (survival rate after challenge inoculation (%)) + (daily weight gain compared with negative control group (%)) - (lesion score × 10) - (fecal oocyst excretion index)

[0088] The challenge inoculation may refer to the administration (e.g., oral inoculation, etc.) of a protozoa capable of inducing coccidiosis. In one embodiment, the survival rate may be the survival rate measured on days 5 to 10, 7 to 10, 8 to 10, 7 to 9, 7 to 8, or 7 after the challenge inoculation. The survival rate may be measured by excluding the number of subjects who died of causes other than coccidiosis through autopsy.

[0089] The weight gain compared to the negative control group in the above-mentioned Equation 1 may be a value calculated by percentage calculated based on the value of the negative control group (eg, a negative control group not infected with protozoa).

[0090] The lesion score in equation 1 above is as described above.

[0091] In the above equation 1, by calculating the percentage based on the value of the negative control group (for example, the negative control group infected with protozoa), when the value of the calculated result is at a level of greater than 0% to less than 1%, the fecal oocyst excretion index may be a value of 0; when the value of the calculated result is at a level of greater than 1% to less than 26%, the fecal oocyst excretion index may be a value of 5; when the value of the calculated result is at a level of greater than 26% to less than 51%, the fecal oocyst excretion index may be a value of 10; when the value of the calculated result is at a level of greater than 51% to less than 76%, the fecal oocyst excretion index may be a value of 20; and when the value of the calculated result is at a level of greater than 76% to less than 100%, the fecal oocyst excretion index may be a value of 40.

[0092] In one embodiment, when the active ingredient (the compound of Chemical Formula 1 or a salt thereof) is included within the above range, its anticoccidial activity may be excellent compared to the case where the active ingredient is included outside the above range.

[0093] In the present application, "feed" may refer to any natural or artificial diet, meal, etc., or a component of a meal, for consumption, ingestion and digestion by animals or suitable therefor. In a feed composition according to one embodiment, concentrated feed and / or special feed may be further included. Concentrated feed is a by-product obtained by purifying seeds, fruits and grains, including grains such as wheat, oats, corn, etc., and may be bran, including rice bran, wheat bran, barley bran, etc.; sesame cake, which is a by-product obtained by squeezing oil from soybeans, fluids, sesame seeds, linseeds, coconut trees, etc.; and residues such as residual starch, which is the main component of starch residue and is the remaining part after removing starch from sweet potatoes and potatoes; fish solubles, which are obtained by concentrating fresh liquid obtained from fish meal, fish waste and fish; animal feed, such as dry whey, wherein whey is the remaining part after producing casein from meat meal, blood meal, feather meal, skimmed milk powder, cheese milk, skimmed milk, etc.; yeast, chlorella and / or seaweed, etc.

[0094] According to one embodiment, a feed composition may refer to a feed in a form that is ultimately ingested by an animal, a dietary supplement that can be mixed with a feed, and / or a feed additive. A dietary supplement is, for example, a composition containing a preparation that provides a therapeutic agent or digestive agent to an animal, and may refer to a composition that is not a common source of calories, i.e., a source of energy, taken in addition to normal animal feed. A feed additive refers to a substance added to the feed for the purpose of various effects, such as supplementing nutrition and preventing weight loss, improving the digestibility of fiber in the feed, alleviating the quality of the oil, preventing proliferation disorders and enhancing fertility, preventing high temperature stress in summer, etc. In one embodiment, a feed additive may refer to a substance added for the purpose of preventing, alleviating or treating coccidiosis.

[0095] In one aspect, a pharmaceutical composition for preventing or treating coccidiosis may be provided, comprising a compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. The compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof is as described above.

[0096] The pharmaceutical composition according to one embodiment can be used as a single preparation, and can be used by further comprising an approved pharmaceutical composition known to have a preventive or therapeutic effect on coccidiosis to prepare a mixed preparation. A unit dosage form of the drug can be prepared by adding a pharmaceutically acceptable carrier, excipient or diluent.

[0097] In this application, "pharmaceutically acceptable" means having no significant irritating effect on organisms and not inhibiting the biological activity and properties of the administered active substance. A pharmaceutical composition comprising a pharmaceutically acceptable carrier according to one embodiment may have any formulation selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, internal solutions, emulsions, syrups, sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried formulations, and suppositories.

[0098] The pharmaceutical composition may be a variety of oral or parenteral preparations. In the case of preparations, conventional fillers, extenders, binders, wetting agents, disintegrants, diluents such as surfactants or excipients may be used for preparation.

[0099] Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., which can be prepared by mixing at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. into one or more compounds. In addition, lubricants such as magnesium stearate, talc, etc. can be used in addition to simple excipients. Liquid preparations for oral administration can also include suspensions, internal solutions, emulsions, syrups, etc., and various excipients such as wetting agents, sweeteners, spices, preservatives, etc., in addition to the commonly used simple diluents water and liquid paraffin.

[0100] Preparations for parenteral administration can include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. As non-aqueous solutions and suspensions, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injection esters such as ethyl oleate can be used. As the matrix of suppositories, polyethylene glycol fatty acid esters, Tween 61, cocoa butter, laurel fat, glycerin gelatin, etc. can be used.

[0101] In one embodiment, the pharmaceutical composition can be formulated into various forms according to common methods for various purposes of use, such as oral preparations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, and injectable preparations such as sterile injection solutions, and can be administered orally or through various routes including intravenous administration, intraperitoneal administration, subcutaneous administration, rectal administration, and topical administration.

[0102] In one embodiment, the pharmaceutical composition may further comprise a carrier, excipient or diluent, and examples of suitable carriers, excipients or diluents may include lactose, glucose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, amorphous cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oil, etc. In addition, the pharmaceutical composition may further comprise a filler, an anticoagulant, a lubricant, a wetting agent, a flavoring agent, an emulsifier, a preservative, etc.

[0103] In one embodiment, the effective amount of the active ingredient (the compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof) in the pharmaceutical composition may vary according to the age, sex and weight of the patient (subject), and generally, 0.0001 mg / kg to 100 mg / kg, 0.0001 mg / kg to 50 mg / kg, 0.0001 mg / kg to 30 mg / kg, 0.0001 mg / kg to 20 mg / kg, 0.0001 mg / kg to 10 mg / kg, 0.0001 mg / kg to 1 mg / kg, 0.0001 mg / kg to 0.1 mg / kg, 0.0001 mg / kg to 0. 01mg / kg, 0.0001mg / kg~0.001mg / kg, 0.001mg / kg~100mg / kg, 0.001mg / kg~50mg / kg, 0.001mg / kg~30mg / kg, 0.001mg / kg~20mg / kg, 0.001 mg / kg~10mg / kg, 0.001mg / kg~1mg / kg, 0.001mg / kg~0.1mg / kg, 0.001mg / kg~0.01mg / kg, 0.01mg / kg~100mg / kg, 0.01mg / kg~50mg / kg, 0.01 mg / kg~30mg / kg, 0.01mg / kg~20mg / kg, 0.01mg / kg~10mg / kg, 0.01mg / kg~1mg / kg, 0.01mg / kg~0.1mg / kg, 0.1mg / kg~100mg / kg, 0.1mg / kg~ 50mg / kg, 0.1mg / kg~30mg / kg, 0.1mg / kg~20mg / kg, 0.1mg / kg~10mg / kg, 0.1mg / kg~1mg / kg, 1mg / kg~100mg / kg, 1mg / kg~50mg / kg, 1mg / kg~3 0mg / kg, 1mg / kg~20mg / kg, 1mg / kg~10mg / kg, 10mg / kg~100mg / kg, 10mg / kg~50mg / kg, 10mg / kg~30mg / kg, 10mg / kg~20mg / kg, 20mg / kg~100mg / kg, 20mg / kg~50mg / kg, 20mg / kg~30mg / kg, 30mg / kg~100mg / kg, 30mg / kg~50mg / kg or 50mg / kg~100mg / kg of every kg body weight can be administered every day or every other day, or divided into 1 to 3 administrations every day. However, because it can increase or decrease according to route of administration, severity of disease, sex, body weight, age etc., the dosage does not limit the scope of the application in any way.In one embodiment, when the composition is administered intraperitoneally, the composition may be administered at a concentration of 0.001 mg / kg to 30 mg / kg.

[0104] In one embodiment, the dosage of the pharmaceutical composition can be within various ranges depending on the patient's weight, age, sex, health condition, diet, administration time, administration method, excretion rate, severity of the disease, and the like.

[0105] In one embodiment, the compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof can be included in the pharmaceutical composition in the following amounts: 1 w / w% or less, less than 1 w / w%, 10 -1 w / w% or less, 5×10 -2 w / w% or less, 2.5×10 -2 w / w% or less, 2×10 -2 w / w% or less, 1.25×10 -2 w / w% or less, 10 -2 w / w% or less, 9×10 -3 w / w% or less, 8×10 -3 w / w% or less, 7×10 -3 w / w% or less, 6×10 -3 w / w% or less, 5×10 -3 w / w% or less, 4×10 -3 w / w% or less, 10 -7 w / w% or more, 10 -6 w / w% or more, 10 -5 w / w% or more, 10 -4 w / w% or more, 5×10 -4 w / w% or more, 10 -3 w / w% or more, 1.5×10 -3 w / w% or more, 2×10 -3 w / w% or more, 3×10 -3 w / w% or more, 4×10 -3 w / w% or more, 5×10 -3 w / w% or more, 10 -7 w / w%~1w / w%、10 -7 w / w%~10 -1 w / w%, 10 -7 w / w%~5×10 -2 w / w%, 10 -7 w / w%~10 -2 w / w%, 10 -7 w / w%~5×10 -3 w / w%, 10 -7 w / w%~4×10-3 in / in%、10 - 7 w / w%~10 -3 in / in%、10 -7 w / w%~5×10 -4 in / in%、10 -7 w / w%~10 -4 in / in%、10 -7 w / w%~10 -5 in / in%、10 -6 in / in%~1in / in%、10 -6 w / w%~10 -1 in / in%、10 -6 w / w%~5×10 -2 in / in%、10 -6 w / w%~10 - 2 in / in%、10 -6 w / w%~5×10 -3 in / in%、10 -6 w / w%~4×10 -3 in / in%、10 -6 w / w%~10 -3 in / in%、10 -6 w / w%~5×10 -4 in / in%、10 -6 w / w%~10 -4 in / in%、10 -6 w / w%~10 -5 in / in%、10 -5 in / in%~1in / in%、10 - 5 w / w%~10 -1 in / in%、10 -5 w / w%~5×10 -2 in / in%、10 -5 w / w%~10 -2 in / in%、10 -5 w / w%~5×10 - 3 in / in%、10 -5 w / w%~4×10 -3 in / in%、10 -5 w / w%~10 -3 in / in%、10 -5 w / w%~5×10 -4 in / in%、10 -5 w / w%~10 -4 in / in%、10 -4w / w% to 1 w / w%, 10 -4 w / w% to 10 -1 w / w%, 10 -4 w / w% to 5×10 -2 w / w%, 10 - 4 w / w% to 10 -2 w / w%, 10 -4 w / w% to 5×10 -3 w / w%, 10 -4 w / w% to 4×10 -3 w / w%, 10 -4 w / w% to 10 - 3 w / w%, 10 -4 w / w% to 5×10 -4 w / w%, 10 -3 w / w% to 1 w / w%, 10 -3 w / w% to 10 -1 w / w%, 10 -3 w / w% to 5×10 -2 w / w%, 10 -3 w / w% to 10 -2 w / w%, 10 -3 w / w% to 5×10 -3 w / w%, 10 -3 w / w% to 4×10 -3 w / w%, 10 -3 w / w% to 2×10 -3 w / w% or 10 -3 w / w% to 1.5×10 -3 w / w%.

[0106] In one embodiment, the compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof can be included in the pharmaceutical composition at a concentration of 10000 ppm or less, 5000 ppm or less, 2000 ppm or less, 1000 ppm or less, 500 ppm or less, 400 ppm or less, 300 ppm or less, 250 ppm or less, 200 ppm or less, 125 ppm or less, less than 125 ppm, 100 ppm or less, 90 ppm or less, 80 ppm or less, 70 ppm or less, 65 ppm or less, 60 ppm or less, 50 ppm or less, 40 ppm or less, 0.001 ppm or more, 0.01 ppm or more, 0.1 ppm or more, 1 ppm or more Above, above 5ppm, above 10ppm, above 15ppm, above 20ppm, above 30ppm, above 40ppm, above 50ppm, 0.001ppm~1000ppm, 0.001ppm~500ppm, 0.001ppm~300ppm, 0.001ppm~200ppm, 0.0 01ppm~125ppm, 0.001ppm~100ppm, 0.001ppm~90ppm, 0.001ppm~80ppm, 0.001ppm~70ppm, 0.001ppm~60ppm, 0.001ppm~50ppm, 0.001ppm~40ppm, 0.001p pm~30ppm, 0.003ppm~1000ppm, 0.003ppm~500ppm, 0.003ppm~300ppm, 0.003ppm~200ppm, 0.003ppm~125ppm, 0.003ppm~100ppm, 0.003ppm~90ppm, 0.00 3ppm~80ppm, 0.003ppm~70ppm, 0.003ppm~60ppm, 0.003ppm~50ppm, 0.003ppm~40ppm, 0.003ppm~30ppm, 0.01ppm~1000ppm, 0.01ppm~500ppm, 0.01ppm~ 300ppm, 0.01ppm~200ppm, 0.01ppm~125ppm, 0.01ppm~100ppm, 0.01ppm~90ppm, 0.01ppm~80ppm, 0.01ppm~70ppm, 0.01ppm~60ppm, 0.01ppm~50ppm, 0.0 1ppm~40ppm, 0.01ppm~30ppm, 0.1ppm~1000ppm, 0.1ppm~500ppm, 0.1ppm~300ppm, 0.1ppm~200ppm, 0.1ppm~125ppm, 0.1ppm~100ppm, 0.1ppm~90ppm, 0.1ppm~80ppm, 0.1ppm~70ppm, 0.1ppm~60ppm, 0.1ppm~50ppm, 0.1ppm~40ppm, 0.1ppm~30ppm, 1ppm~1000p pm, 1ppm~500ppm, 1ppm~300ppm, 1ppm~200ppm, 1ppm~125ppm, 1ppm~100ppm, 1ppm~90ppm, 1ppm~80ppm, 1 ppm~70ppm, 1ppm~60ppm, 1ppm~50ppm, 1ppm~40ppm, 1ppm~30ppm, 3ppm~1000ppm, 3ppm~500ppm, 3ppm~30 0ppm, 3ppm~200ppm, 3ppm~125ppm, 3ppm~100ppm, 3ppm~90ppm, 3ppm~80ppm, 3ppm~70ppm, 3ppm~60ppm, 3 ppm~50ppm, 3ppm~40ppm, 3ppm~30ppm, 5ppm~1000ppm, 5ppm~500ppm, 5ppm~300ppm, 5ppm~200ppm, 5ppm~ 125ppm, 5ppm~100ppm, 5ppm~90ppm, 5ppm~80ppm, 5ppm~70ppm, 5ppm~60ppm, 5ppm~50ppm, 5ppm~40ppm, 5 ppm~30ppm, 10ppm~1000ppm, 10ppm~500ppm, 10ppm~300ppm, 10ppm~200ppm, 10ppm~125ppm, 10ppm~100p pm, 10ppm~90ppm, 10ppm~80ppm, 10ppm~70ppm, 10ppm~60ppm, 10ppm~50ppm, 10ppm~40ppm or 10ppm~30ppm. .

[0107] In one embodiment, the pharmaceutical composition can be administered to a subject by a variety of routes. Administration can refer to providing a substance to a subject (patient) by any suitable method, and the route of administration of the pharmaceutical composition can be oral administration and / or parenteral administration, by all conventional routes, as long as the target tissue is reached. In the case of parenteral administration, external application to the skin, intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection and / or thoracic injection can be selected. In addition, the composition according to an embodiment can be administered using any device that can deliver the active ingredient to the target cell.

[0108] In one aspect, an antiprotozoal composition for use against Eimeria protozoa is provided, comprising at least one compound selected from the group consisting of compounds of Chemical Formula 1 and salts thereof. The compound of Chemical Formula 1, salts thereof, and / or Eimeria protozoa are as described above.

[0109] In one embodiment, the antiprotozoal activity (action, efficacy) against Eimeria protozoa is excellent, which may refer to the following characteristics (1) and / or (2), for example, compared with a control group (negative control group and / or positive control group), it may exhibit the following characteristics (1) and / or (2):

[0110] (1) having excellent killing effect on Eimeria protozoa; and / or

[0111] (2) Inhibit the cell invasion of Eimeria protozoa and / or inhibit the proliferation of protozoa in cells.

[0112] In one embodiment, in a pharmaceutical composition, the compound of Chemical Formula 1 or a salt thereof can be included in the antiprotozoal composition within the above-mentioned concentration range. In one embodiment, a composition including an active ingredient within the above-mentioned concentration range can have superior antiprotozoal activity compared to a composition including an active ingredient outside of the above-mentioned concentration range.

[0113] On the other hand, a method for preventing, alleviating or treating coccidiosis can be provided, comprising administering the composition (e.g., a pharmaceutical composition and / or an antiprotozoal composition) to an animal. In one embodiment, prior to administering the composition, the method may further comprise confirming (selecting) a subject (patient) in need of preventing, alleviating or treating coccidiosis. The composition and coccidiosis are as described above. According to one embodiment, confirming the subject may comprise detecting oocysts of a protozoan capable of inducing coccidia in feces isolated from the subject.

[0114] In the method for preventing, alleviating or treating coccidiosis according to one embodiment, the administration method, administration route and / or administration dosage of the composition are as described above.

[0115] According to one embodiment, the composition can be administered with a pharmaceutically effective dose. In the present application, " pharmaceutically effective dose " refers to the amount that is enough to treat the disease under the reasonable benefit / risk ratio that is applicable to medical treatment, and effective dose level can be determined according to the patient's disease type, severity, drug activity, sensitivity to the drug, administration time, route of administration and excretion ratio, treatment cycle, the element comprising the drug used simultaneously and other elements known to the medical field. According to one embodiment, the composition can be used as a single therapeutic agent administration or co-administered with other anticoccidial agents, and can be administered simultaneously with conventional therapeutic agents, separately administered or administered successively, and can be single or multiple administration. Taking all factors into consideration, it is important to give the amount that can obtain maximum effect with minimum amount when there is no side effect, and this can be simply determined by those skilled in the art.

[0116] In one embodiment, the subject to which the method for preventing, slowing down or treating coccidiosis is applied refers to an animal that has or may develop coccidiosis, and the animal can be a mammal, including humans, horses, cows, mice, rats, dogs, cats, etc., birds including poultry (such as breeders, broilers and / or laying hens, etc.), fish, amphibians and / or reptiles, etc.

[0117] In one embodiment, the animal used in the method for preventing, alleviating or treating coccidiosis can be at least one selected from the group consisting of the animals described in Table 1 above, for example, the animal can be at least one selected from the group consisting of humans, chickens, ducks, geese, turkeys, quails, pheasants, pigeons, parrots, cattle, pigs, goats, sheep, horses, antelopes, elands, monkeys, cats, dogs, mice, rats, rabbits, raccoons, squirrels, bats, guinea pigs, camels, llamas, alpacas, wombats, lizards, goldfish, crucian carp, tilapia, barbell fish, lungfish and whitefish. In one embodiment, the animal can be an animal other than humans.

[0118] In other aspects, there is provided a use of a compound of Chemical Formula 1 or a salt thereof in preparing a composition (e.g., a pharmaceutical composition) for preventing, alleviating, and / or treating coccidiosis or in preparing an antiprotozoal composition; the use of a compound of Chemical Formula 1 or a salt thereof for preventing, alleviating, and / or treating coccidiosis; and / or the use of a compound of Chemical Formula 1 or a salt thereof for antiprotozoal treatment of Eimeria protozoa (e.g., killing Eimeria protozoa; and / or inhibiting cell invasion and / or proliferation of Eimeria protozoa). In the above uses, the compound of Chemical Formula 1 or a salt thereof, coccidiosis, antiprotozoa, and Eimeria protozoa are as described above.

[0119] Beneficial effects

[0120] The composition comprising the compound or a salt thereof according to one embodiment has an excellent direct killing effect on protozoa capable of inducing coccidiosis, an inhibitory effect on cell invasion of protozoa and / or an inhibitory effect on proliferation of protozoa in cells, and has excellent preventive, alleviating and therapeutic effects on coccidiosis in vivo. DETAILED DESCRIPTION

[0121] Hereinafter, the present invention will be described in more detail by the following examples. However, the examples are only for illustrating the present invention, and the scope of the present invention is not limited by these examples.

[0122] The present application will be described in more detail through the following examples, but the scope is not intended to be limited by the following examples.

[0123] Example 1. In vivo anticoccidial activity of stilbenes

[0124] Example 1-1. Experimental facilities and study design

[0125] The in vivo anticoccidial efficacy evaluation test was conducted at an animal experimental facility in Gyeongsangnam-do, South Korea. One-day-old female Ross broilers were individually weighed and randomly divided into groups for the experiment. The experimental design and conditions are described in Table 2.

[0126] Table 2

[0127]

[0128]

[0129] The farm was managed according to the Korean Poultry Farming Management Guidelines. Before the start of the experiment, the cages and farm were cleaned and disinfected. The farm maintained a temperature of 40°C to 41°C and a humidity of 40% to 50% and was continuously monitored. Broilers were fed a general feed based on their nutritional requirements, with the mix ratios described in Table 3.

[0130] Table 3

[0131] raw material(%) content corn 69.01 soybean flour 23.99 soybean oil 2.75 Dicalcium phosphate 2 calcium carbonate 1.4 Salt 0.35 Poultry Vitamin Mix 0.2 Poultry Mineral Mix 0.15 DL-methionine 0.1 Choline chloride, 60% 0.05 Total 100 Calculated value (DM basis, %) CP, % 16 Ca, % 1.19 Available phosphorus (Avail.P), % 0.54 Lysine, % 1 Methionine, % 0.42 Cysteine ​​+ methionine, % 0.65 TMEn, kcal / kg 3585

[0132] Example 1-2. Experimental Design

[0133] To the general feed (Table 3), various materials (salinomycin (CAS No. 53003-10-4.), resveratrol (Sigma) or pterostilbene (Sigma)) were added at the concentrations described in Table 4 below and self-mixed.

[0134] The standard feed and mixed feeds were free of antibiotics and supplements, and no anticoccidial agents were added beyond the individual ingredients. Broilers were fed ad libitum throughout the experimental period. Six one-day-old broilers were randomly placed in cages for each control or experimental group and housed. After being fed a standard feed for 14 days, the mixed feed prepared above was then distributed to the control or experimental group.

[0135] Coccidiosis was induced by oral inoculation in oral casts (challenge inoculation) with 10,000 oocysts (eggs) of Eimeria tenella that were more than 90% mature (sporulated) per bird at 21 days of age.

[0136] Table 4

[0137] Group deal with Uninfected negative control group General feed Infected negative control group Eimeria tenella infection + general feed Positive control group Eimeria tenella infection + compound feed containing 60ppm salinomycin Resveratrol-treated group Eimeria tenella infection + compound feed containing 125ppm resveratrol Pterostilbene treatment group Eimeria tenella infection + compound feed containing pterostilbene 125ppm

[0138] Example 1-3. Determination of the anticoccidial activity of stilbenes

[0139] The anticoccidial effect of the test group designed in the above Examples 1-2 was expressed as an anticoccidial index (ACI), which was calculated by the following equation 2. The ACI score is a full score of 200 points, the higher the ACI score, the more excellent the anticoccidial ability, and when the ACI score is 120 points or more and less than 140 points, it is determined to be effective as an anticoccidial material, and when the ACI score is 140 points or more and less than 160 points, it is determined to be excellent as an anticoccidial material, and when the ACI score is 160 points or more, it is determined that the anticoccidial effect is very excellent (Luis Miguel De Pablos et al., Anticoccidial activity of maslinic acid against infection with Eimeria tenella in chickens, Parasitol Res, 2010).

[0140] (Equation 2)

[0141] Anticoccidial index (ACI) = (survival rate after challenge inoculation (%)) + (daily body weight gain (RWG, %) compared with the negative control group) - (lesion score × 10) - (fecal oocyst excretion index)

[0142] 1) Survival Rate: The number of individuals who died was recorded daily, and postmortems were performed to determine the cause of death. Individuals who died due to causes other than coccidiosis were excluded. The survival rate (%) from the 8th day after challenge inoculation was used to calculate the anticoccidial index. The measured survival rates are described in Table 5 below.

[0143] 2) Daily Weight Gain: The body weight of each cage was measured before and 7 days after the protozoan challenge inoculation, and the difference was divided by the number of days to calculate the daily weight gain (ADG, g / day). "Daily weight gain compared to the negative control group (RWG, %)" was calculated by dividing the daily weight gain (ADG, average daily gain; g / day) of each experimental group by the weight gain (ADG, g / day) of the uninfected negative control group and multiplying by 100. This was used for the calculation of the anticoccidial index. The daily weight gain (ADG, g / day) measured in each control group and the experimental group and the daily weight gain (RWG, %) compared to the negative control group are shown in Table 5 below.

[0144] 3) Lesion Scoring: On day 8 after challenge inoculation, 6 broiler chickens per cage were necropsied, their intestines cut open, and their intestines opened. Each coccidial lesion in the appendix region of the broiler chickens was scored. The lesion scoring method was based on the literature of Johnson JK & Reid WM (1970) (Joyce Johnson and W. Malcolm Reid, Anticoccidial drugs: Lesion scoring techniques in battery and floor-pen experiments with chickens, Experimental parasitology, 1970). The lesion score ranges from 0 to 4, with 0 corresponding to a normal appendix, 1 for mild infection symptoms, 2 for moderate infection symptoms, 3 for severe infection symptoms, and 4 for very severe infection symptoms or death. The measured appendix lesion score was multiplied by 10 to calculate the lesion index, which was used to calculate the anticoccidial index. The lesion scores and lesion indices measured in each control and test group are described in Table 5 below.

[0145] 4) Fecal Oocyst Excretion: All feces from day 6 to day 8 of challenge inoculation were collected using a cage, mixed, and randomly sampled three times, 1 gram each time. Oocysts were floated in saline, and oocyst excretion was measured using a McMaster chamber. The results are shown in Table 5 below. Data were statistically analyzed using a SAS mixed model (PROC MIXED). Data with a significant difference of p < 0.05 are indicated with a superscript. Oocyst excretion (%) compared to the infected negative control group was calculated by dividing the oocyst excretion of each group by the oocyst excretion of the infected negative control group and multiplying by 100. When the calculated oocyst excretion was at a level of 0% to less than 1% compared to the infected negative control group, the oocyst excretion index was calculated as 0; when it was at a level of more than 1% to less than 26%, the fecal oocyst excretion index was calculated as 5; when it was at a level of more than 26% to less than 51%, the fecal oocyst excretion index was calculated as 10; when it was at a level of more than 51% to less than 76%, the fecal oocyst excretion index was calculated as 20; and when it was at a level of more than 76% to less than 100%, the fecal oocyst excretion index was calculated as 40. The results are described in Table 5 below, which was used to calculate the anticoccidial index.

[0146] Table 5

[0147]

[0148]

[0149] As described above, the anticoccidial index of each test group measured by the above equation 2 is shown in Table 5 above.

[0150] As shown in Table 5, compared with the negative control group that was not infected, weight gain decreased in the negative control group infected with Eimeria tenella, and lesion index and feces oocyst excretion increased. Compared with the negative control group that was infected, the increase effect (p < 0.05) of weight gain and the reduction effect (p < 0.05) of lesion score and oocyst excretion were demonstrated in the salinomycin treated group used as the positive control group. Resveratrol or pterostilbene treated group demonstrated the effect that was equal to or better than that of the salinomycin treated group. Therefore, resveratrol or pterostilbene treated group demonstrated the significant improvement of weight gain and the significant reduction of lesion index and oocyst excretion. As the result of calculating and comparing the anticoccidial index, resveratrol (149 points) and pterostilbene (151 points) demonstrated the anticoccidial efficacy that was equal to or better than that of anticoccidial agent salinomycin (149 points).

[0151] Example 2. Direct killing effect of stilbenoid compounds against Eimeria protozoa

[0152] In this example, the direct protozoal (sporozoite) killing ability of a representative Eimeria species (Eimeria tenella) known to infect most farms was evaluated.

[0153] A certain amount of oocysts of each coccidian protozoan was placed in a test tube containing glass beads and crushed. The crushed oocyst cell walls and other debris were then removed and the internal sporocysts were purified using a Percoll density gradient and washed with a PBS solution. Sporocysts of Eimeria tenella were treated with reagents containing sodium taurocholate (Sigma Aldrich, USA) and trypsin (Gibco, USA) to excyst the internal sporozoites, incubated, and then washed once with a PBS solution to obtain protozoa.

[0154] Pterostilbene, pinostilbene, and the anticoccidial agents diclazuril and gallic acid (hereinafter, "Materials") were reacted with Eimeria tenella protozoa at various concentrations ranging from 16 ppm to 500 ppm. Only live protozoa (sporozoites) were counted under a microscope. Table 6 below shows the direct mortality rate (%) of the protozoa by material concentration.

[0155] Table 6

[0156]

[0157]

[0158] As shown in Table 6 above, the gallic acid and diclazuril treatment groups did not show a 50% or greater mortality rate against protozoa (sporozoites) capable of inducing coccidia at doses below 500 ppm. The pterostilbene treatment group showed a 50% or greater mortality rate against Eimeria tenella protozoa at doses above 32 ppm, confirming a very excellent protozoicide activity. Furthermore, pine stilbene showed a 50% or greater mortality rate against protozoa at doses above 250 ppm, thus confirming a remarkably excellent protozoicide activity.

[0159] Through the above description, it will be understood by those skilled in the art that the present application may be implemented in other specific forms without changing the technical spirit or essential features. In this regard, it should be understood that the embodiments described above are illustrative rather than restrictive in all respects. The scope of the present application should be interpreted as being included within the scope of the present application and all changes or modifications and equivalent concepts derived from the meaning and scope of the claims described below, rather than the detailed description above.

Claims

1. Use of a compound of the following chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient in the preparation of a pharmaceutical composition for preventing, alleviating or treating coccidiosis: [Chemical Formula 1] In Chemical Formula 1, R1 is OCH3 and R2 is OCH3; or R1 is OH and R2 is OCH3.

2. The use according to claim 1, wherein The coccidiosis is caused by protozoa of the genus Eimeria sp.

3. The use according to claim 1, wherein: The prevention, alleviation or treatment of coccidiosis is at least one selected from the group consisting of the following (1) to (4): (1) reducing at least one of the following: lesion score, fecal oocyst excretion, and mortality; (2) Inhibit weight loss caused by coccidiosis; (3) increase the anticoccidial index (ACI); and (4) Reducing cell invasion by Eimeria protozoa, proliferation of protozoa in cells, or both.

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