Anti-coccidial composition comprising quinic acid and uses thereof

Abstract

The present application relates to a composition comprising quinic acid for preventing, alleviating, or treating coccidiosis, and an anti-protozoan composition against sporozoites of the genus Eimeria.

Description

Anticoccidial composition containing quinic acid and use thereof

[0001] Cross-citation with related application(s)

[0002] This application claims the benefit of priority from Republic of Korea Patent Application No. 10-2023-0103638, dated August 8, 2023, the entire contents of which are incorporated herein by reference.

[0003] The present application relates to the anticoccidial use of quinic acid and / or its salts.

[0004]

[0005] Coccidiosis is an intestinal disease caused by protozoan parasites belonging to the phylum apicomplexan, called Eimeria. Infection with coccidiosis causes symptoms such as indigestion, diarrhea, and weight loss, and can even lead to livestock death, and has a significant economic impact on farms worldwide (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).

[0006] Over the past several years, numerous research teams have developed anticoccidial agents, such as ionophores or chemically synthetic compounds, that can inhibit oocyst cell wall formation or the asexual and sexual reproduction of protozoa. However, long-term use of shuttle programs, which alternate between ionophores and chemically synthetic compounds, has resulted in adverse effects, such as the emergence of drug-resistant protozoa.

[0007] In particular, antibiotic overuse and misuse have led to the accumulation of antibiotics in animals, leading to human consumption of antibiotics through meat, posing a serious problem. Furthermore, countries around the world are banning antibiotic use due to the issue of antibiotic residues in livestock products. Therefore, there is an urgent need for research and development of alternatives to existing anticoccidial agents, which have side effects such as the emergence of drug-resistant strains and the potential for residual antibiotics in the body.

[0008]

[0009] [Prior Art Literature]

[0010] (Patent Document 1) U.S. Patent Publication No. US 2003-0091589 A1 (Published May 15, 2003)

[0011]

[0012] The purpose of the present application is to provide a use for quinic acid and / or its salts for preventing, ameliorating, and / or treating coccidiosis.

[0013] Another object of the present application is to provide a feed composition for preventing or improving coccidiosis, comprising quinic acid and / or a salt thereof.

[0014] Another object of the present application is to provide a pharmaceutical composition for preventing or treating coccidiosis comprising quinic acid and / or a salt thereof.

[0015] Another object of the present application is to provide a use of quinic acid and / or its salts for the preparation of a composition (feed composition, pharmaceutical composition) for preventing, treating and / or treating coccidiosis.

[0016] Another object of the present application is to provide a method for preventing, ameliorating, and / or treating coccidiosis, comprising administering quinic acid and / or a salt thereof to a subject in need of prevention, amelioration, and / or treatment of coccidiosis. The method may further comprise, prior to the administering step, a step of identifying a subject in need of prevention, amelioration, and / or treatment of coccidiosis.

[0017] Another object of the present application is to provide an antiprotozoal use of quinic acid and / or its salts against protozoa of the genus Eimeria.

[0018] Another object of the present application is to provide an antiprotozoal composition against protozoa of the genus Aemeria comprising quinic acid and / or a salt thereof.

[0019] Another object of the present application is to provide a use of quinic acid and / or its salts for the preparation of an antiprotozoal composition against protozoa of the genus Eimeria.

[0020] Another object of the present application is to provide a method for controlling protozoa of the genus Eimeria, comprising the step of administering quinic acid and / or a salt thereof to a subject in need of controlling protozoa of the genus Eimeria.

[0021]

[0022] This is specifically explained as follows. Meanwhile, each description and embodiment disclosed in this application can also be applied to each other description and embodiment. That is, all combinations of the various elements disclosed in this application fall within the scope of this application. Furthermore, the scope of this application is not limited by the specific descriptions described below. Furthermore, those skilled in the art will recognize or ascertain numerous equivalents to the specific embodiments of this application described in this application using only routine experimentation. Furthermore, such equivalents are intended to be encompassed by this application.

[0023]

[0024] The present application is described in more detail below.

[0025]

[0026] One aspect provides a composition for preventing, improving, and / or treating coccidiosis, comprising quinic acid and / or a salt thereof.

[0027] Another aspect provides the use of quinic acid and / or its salts in the manufacture of a composition for preventing, treating and / or treating coccidiosis.

[0028] Another aspect provides a method for preventing, ameliorating, and / or treating coccidiosis, comprising administering quinic acid and / or a salt thereof to a subject in need of such prevention, amelioration, and / or treatment. The method may further comprise, prior to the administering step, identifying a subject in need of coccidiosis prevention, amelioration, and / or treatment. In one example, the step of identifying the subject may comprise detecting oocysts of a protozoan capable of inducing coccidiosis in feces isolated from the subject.

[0029] The composition for preventing, improving, and / or treating coccidiosis may be a feed composition or a pharmaceutical composition.

[0030]

[0031] In the present application, quinic acid may be a compound having a structure of the following chemical formula 1 (C7H 12 O 6, Cas No. 77-95-2, PubChem CID NO. 6508).

[0032] [Chemical Formula 1]

[0033]

[0034] The above quinic acid or its salt can be purchased commercially, obtained by extraction and separation from a natural product or strain, or manufactured by a conventional organic synthesis method, but is not limited thereto.

[0035] In the present specification, the salt of quinic acid may refer to a physiologically acceptable salt among salts in which cations and anions are bonded by electrostatic attraction, and may refer to, for example, a salt acceptable for a feed composition, a pharmaceutically acceptable salt, and / or a salt acceptable for an anti-protozoal 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 example, 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, etc.; The salt with an organic base may be at least one selected from the group consisting of salts with triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine, N,N-dibenzylethylenediamine, etc.; The salt with an inorganic acid may be at least one selected from the group consisting of salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, etc.; 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.; 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.

[0036] In the present application, excellent anticoccidial efficacy (activity, effect) may mean one or more (e.g., one or more, two or more, three or more, or all four) selected from the group consisting of the following (1) to (4):

[0037] (1) Anticoccidial index (ACI) is higher than that of the control group;

[0038] (2) Administered to animals in which coccidiosis has been induced to reduce mortality, lesion score (e.g., cecal lesion score), and / or fecal oocyst excretion compared to the control group;

[0039] (3) Inhibition of weight loss caused by coccidiosis; and

[0040] (4) Higher insecticidal activity against protozoa that induce coccidiosis compared to the control group.

[0041] In the present application, the control group may mean a negative control group (a group treated with nothing or a group treated with water and / or buffer) and / or a positive control group including a known anticoccidial agent (e.g., diclazuril and / or salinomycin).

[0042] A composition according to an example may have one or more properties (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 (1) to (6), and the properties may be superior to those of a control group:

[0043] (1) Excellent anticoccidial activity;

[0044] (2) Excellent antiprotozoal effect against protozoa that cause coccidiosis;

[0045] (3) Excellent acid resistance;

[0046] (4) Excellent heat resistance;

[0047] (5) Excellent in vivo stability and / or safety; and

[0048] (6) Excellent effect on improving weight gain.

[0049] A composition according to an example can be administered into the body and maintain excellent anticoccidial activity for a long period of time, has excellent in vivo stability, can maintain excellent anticoccidial activity even in environments with various temperature and / or pH ranges, can be applied to various products (e.g., feed additives), and can have excellent storage stability.

[0050] A composition according to an example may have excellent in vivo safety because it is not absorbed into tissues and organs other than the intestine (e.g., blood, liver, kidney, and / or spleen, etc.) when administered in the body, and thus has a small residual amount in the body.

[0051] In one example, an excellent effect on improving body weight gain may mean that the effect of administering the compound to an individual is excellent in increasing the body weight of the individual, and in one example, the weight gain may mean daily weight gain, and the individual may be an individual in which coccidiosis is induced.

[0052] A composition according to an example exhibits anticoccidial activity equivalent to or greater than that of existing known anticoccidial agents, while not causing side effects or drug resistance, and thus can be safe for long-term use.

[0053] In the present application, "prevention" means any act of inhibiting or delaying the onset of a disease by administering a composition according to an example, "treatment" means any act of improving or beneficially changing the symptoms of a suspected or affected individual by administering a composition according to an example, and "improvement" may mean any act of at least reducing a parameter related to a state in which a disease is treated, for example, the severity of a symptom, by administering a composition according to an example. The disease may refer to coccidiosis.

[0054] In the present application, “coccidiosis” is a disease in which coccidian protozoa (protozoa that can induce coccidiosis, for example, coccidian protozoa of the genus Aemeria) parasitize in the cytoplasm of the submucosal tissue of the digestive tract epithelium, destroying the epithelium and causing enteritis, and is a protozoal disease that causes economic damage in broiler farms due to reduced weight gain and extended slaughter age due to loose stools, diarrhea, and bloody stools. Coccidiosis can occur not only in broiler chickens but also in birds and mammals, and specifically, coccidiosis can infect cattle, rabbits, goats, dogs, cats, laboratory animals such as mice and rats, and can cause fatal damage to poultry such as chickens in particular. In one example, coccidiosis can include acute coccidiosis, subacute coccidiosis, and chronic coccidiosis. The above acute coccidiosis shows bloody stool, lethargy, and anemia within 48 hours after infection, and the infected individual may die. The above subacute coccidiosis may show bloody diarrhea and / or anemia after infection, and the above chronic coccidiosis may show loose stool and / or weight loss after diarrhea for 1 to 2 days after infection.

[0055] When the oocysts (cysts, eggs) of the coccidium protozoan species mature into sporulated oocysts under high humidity and temperature, they become infectious. After going through a certain life cycle in the body of an organism, the oocysts are excreted in the feces, allowing easy transmission and repeating the oocyst life cycle. The oocysts (cysts) of the coccidium protozoan species are highly resistant to the external environment, and the cyst wall is known to be composed of two layers, inner and outer. The outer layer of the cyst wall is a gelatinous substance that strongly resists physical external pressure, and the inner layer is rich in nucleoproteins, making it highly resistant to chemical stimuli such as disinfectants. The oocyst of the Coccidia species may contain four sporocysts, each of which may contain two sporozoites. After infecting an animal in the form of an oocyst, the sporocysts and sporozoites are released to proliferate within the cell, and the sporozoites that have undergone sexual and / or asexual reproduction may form oocysts and be excreted in the feces. In one example, the sporozoites may be used in the same sense as the protozoan, and the sporozoites (protozoa) may cause a lesion.

[0056] In one example, the coccidiosis may be caused by a protozoan of the genus Eimeria (Eimeriasp.). In one example, the protozoa of the genus Eimeria are Eimeria acervulina (sand spore), Eimeria tenella (chicken cecal spore), Eimeria maxima (Eimeria maxima), Eimeria necatrix (Eimeria necatrix), Eimeria brunetti (Eimeria brunetti), Eimeria hagani (Eimeria hagani), Eimeria mitis (Eimeria mitis), Eimeria praecox (Eimeria praecox), Eimeria mivati ​​(Eimeria mivati), Eimeria aurati, Eimeria baueri, Eimeria Eimeria lepidosirenis, Eimeria 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 meleagrimitis, Eimeria phasiani, Eimeria procera, Eimeria purpureicephali, Eimeria ahsata, Eimeria alabamensis, Eimeria alijevi, Eimeria aspheronica, Eimeria arloingi, Eimeria arundeli, Eimeria bakuensis, Eimeria bovis, Eimeria cameli, Eimeria caprina, Eimeria caprovina (Eimeria caprovina), Eimeria christenseni, Eimeria clethrionomyis, Eimeria coecicola, Eimeria contorta, Eimeria couesii, Eimeria crandallis, Eimeria 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 larimerensis, Eimeria macusaniensis, Eimeria magna, Eimeria marconii, Eimeria media, Eimeria melanuri, Eimeria myoxi, Eimeria nagpurensis, Eimeria nieskulzi (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 procyonis, Eimeria punctate, Eimeria roobroucki,It may be at least one species selected from the group consisting of Eimeria saudiensis, Eimeria sealanderi, Eimeria separata, Eimeria stiedae, Eimeria ursini, Eimeria vermiformis, Eimeria weybridgensis, Eimeria wobati, and Eimeria zuernii.

[0057] A composition according to an example may be excellent in the prevention, improvement, and / or treatment of coccidiosis induced by one or more protozoa selected from the group consisting of protozoa of the genus Aemeria listed in Table 1 below, and each of the protozoa of the genus Aemeria listed in Table 1 below may induce coccidiosis in an animal listed in Table 1.

[0058] species host animal 1 Eimeria acervulina chicken (Gallus gallus domesticus) 2 Eimeria tenella chicken (Gallus gallus domesticus) 3 Eimeria maxima chicken (Gallus gallus domesticus) 4 Eimeria necatrix chicken (Gallus gallus domesticus) 5 Eimeria brunetti chicken (Gallus gallus domesticus) 6 Eimeria hagani chicken (Gallus gallus domesticus) 7 Eimeria mitis chicken (Gallus gallus domesticus) 8 Eimeria praecox chicken (Gallus gallus domesticus) 9 Eimeria mivati ​​chicken (Gallus gallus domesticus) 10 Eimeria Eimeria aurati, goldfish (Carassius auratus), 11 Eimeria baueri, crucian carp (Carassius carassius), 12 Eimeria lepidosirenis, South American lungfish (Lepidosiren paradoxa), 13 Eimeria leucisci, common barbel (Barbus barbus bocagei), 14 Eimeria rutile, European chub (Leuciscus cephalus cabeda), Iberian nase (Chondrostoma polylepis polylepis), 15 Eimeria vanasi, blue tilapia (bluetilapia (Oreochromis aureus))16 Eimeria amphisbaeniarum (Eimeria amphisbaeniarum)Mann's worm lizard (Amphisbaena manni))17 Eimeria witchery (Eimeria witchery)Worm lizard (Mann's worm lizard (A. manni))18 Eimeria yemenensae (Eimeria yemenensae)Rock agama (Agama yemenensis))19 Eimeria adenoeides (Eimeria adenoeides)Turkey (Meleagris gallopavo)20 Eimeria colchici (Eimeria colchici)Common pheasant (Phasianus colchicus)21 Eimeria curvata (Eimeria curvata)Ruddy ground dove (Columbina talpacoti)), scaled dove (Scardafella squammata)22Eimeria dispersaTurkey (M. gallopavo)), bobwhite quail (Colinus virginianus)23Eimeria duodenalisPheasant (Common pheasant (Phasianus colchicus)24Eimeria fraterculaeAtlantic puffin (Fratercula arctica)25Eimeria gallopavonisTurkey (M. gallopavo)26Eimeria innocuaTurkey (M. gallopavo)27Eimeria Eimeria meleagridis (turkey (M. gallopavo))28 Eimeria meleagrimitis (turkey)(turkey (M. gallopavo))29Eimeria phasianiPheasant (P. colchicus)30Eimeria proceraGrey partridges (Perdix perdix)31Eimeria purpureicephaliRed-capped parrot (Purpureicephalus spurius)32Eimeria ahsataGoat (Capra hircus)Sheep (Ovis aries)33Eimeria alabamensisCattle (Bos taurus)34Eimeria alijeviGoat (C. hircus)35Eimeria aspheronica)goat (C. hircus)36Eimeria arloingi)goat (C. hircus)37Eimeria arundeli)common wombat (Vombatus ursinus)38Eimeria bakuensis)sheep (O. aries)39Eimeria bovis)cattle (B. taurus)40Eimeria cameli)camels (Camelus bactrianus, Camelus dromedarius)41Eimeria caprina)goat (C. hircus)42Eimeria caprovina)goat (C. hircus))43 Eimeria christenseni goat (C. hircus))44 Eimeria clethrionomyis red-backed vole(Clethrionomys gapperi))45 Eimeria coecicola rabbit (Oryctolagus cuniculus))46 Eimeria contorta mouse (Mus musculus))47 Eimeria couesii rice rat (Oryzomys couesi))48 Eimeria crandallis sheep (O. aries))49 Eimeria dammahensis scimitar-homed oryx (Oryx dammah))50 Eimeria dowleri eastern red bat (Lasiurus borealis))51 Eimeria exigua rabbit (rabbit (O. cuniculus))52Eimeria falciformisMouse (M. musculus))53Eimeria farasaniiMountain gazelle (Gazella gazelle farasani))54Eimeria ferrisiMouse (M. musculus))55Eimeria flavescensRabbit (O. cuniculus))56Eimeria gallatiiRed-backed vole (Clethrionomys gapperi))57Eimeria granulosaGoat (C. hircus))58Eimeria hirciGoat (C. hircus))59Eimeria intestinalis rabbit (O. cuniculus))60Eimeria irresidua rabbit (rabbit(O. cuniculus))61 Eimeria intricata (Eimeria intricata) Goat (C. hircus))62 Eimeria jolchijevi (Eimeria jolchijevi) Goat (C. hircus))63 Eimeria krijgsmanni (Eimeria krijgsmanni) Mouse (M. musculus))64 Eimeria larimerensis (Eimeria larimerensis) Uinta ground squirrel (Spermophilus armatus))65 Eimeria macusaniensis (Eimeria macusaniensis) Llamas (Lama glama)), guanacos (Lama guanicoe)), alpacas (Vicugna pacos)), vicuñas (Vicugna vicugna))66 Eimeria Eimeria magna (rabbit (O. cuniculus)) 67 Eimeria marconii (red-backed vole (Clethrionomys gapperi)) 68 Eimeria media (rabbit (O. cuniculus)) 69 Eimeria melanuri (garden dormouse (Eliomys quercinus)) 70 Eimeria myoxi (garden dormouse (Eliomys quercinus)) 71 Eimeria nagpurensis (rabbit (O. cuniculus)) 72 Eimeria nieschulzi (brown rat (R. norvegicus)) 73 Eimeria Eimeria ninakohlyakimovae goat (C. hircus) 74 Eimeria ovinoidalis sheep (O.aries))75 Eimeria pallida Goat (C. hircus)76 Eimeria palustris Marsh rice rat (Oryzomys palustris)77 Eimeria papillata Mouse (M. musculus)78 Eimeria perforans Rabbit (O. cuniculus)79 Eimeria phocae Sable Island harbor seals (Phoca vitulina)80 Eimeria pileata Red-backed vole (Clethrionomys gapperi)81 Eimeria pipistrellus Cool's house bat (Kuhl's pipistrelle (Pipistrellus kuhlii))82 Eimeria piriformis (Eimeria piriformis)Rabbit (O. cuniculus))83 Eimeria prionotemni (Eimeria prionotemni)Bennett's wallaby (Macropus rufogriseus))84 Eimeria procyonis (Eimeria procyonis)Raccoon (Procyon lotor))85 Eimeria punctate (Eimeria punctate)Goat (C. hircus))86 Eimeria roobroucki (Eimeria roobroucki)Rabbit (O. cuniculus))87 Eimeria saudiensis (Eimeria saudiensis)Arabian oryx (Oryx leucoryx))88 Eimeria Eimeria sealanderi, eastern red bat (Lasiurus borealis), mouse (M.musculus), rat (Rattus rattus) 90 Eimeria stiedae rabbit (O. cuniculus) 91 Eimeria ursini southern hairy-nosed wombat (Lasiorhinus latifrons) 92 Eimeria vermiformis mouse (M. musculus) 93 Eimeria weybridgensis sheep (O. aries) 94 Eimeria wobati southern hairy-nosed wombat (L. latifrons) 95 Eimeria zuernii cattle (B. taurus)

[0059] A composition according to one example may be effective in preventing, ameliorating, and / or treating coccidiosis induced by Eimeria tenella.

[0060] In one example, the prevention or improvement of coccidiosis may mean one or more (e.g., one or more, two or more, three or more, or all four) selected from the group consisting of (1) to (4) below, and for example, one or more (e.g., one or more, two or more, or all three) selected from the group consisting of (1) to (3) below may be reduced, inhibited, and / or increased compared to a control group (negative control group and / or positive control group):

[0061] (1) A decrease in at least one selected from the group consisting of lesion score (e.g., cecal lesion score), fecal oocyst excretion, and mortality rate;

[0062] (2) Inhibition of weight loss caused by coccidiosis; and

[0063] (3) Increase in the anticoccidial index (ACI).

[0064] In one example, the lesion scoring method for determining the lesion score may be performed with reference to the literature (Joyce Johnson, W.Malcolm Reid, Anticoccidial drugs: Lesion scoring techniques in battery and floor-pen experiments with chickens, Experimental parasitology, 1970) by Johnson JK & Reid WM, and the lesion score may be graded from 0 to 4. In one example, the lesion score may refer to a lesion score measured in the cecum, duodenum, and / or jejunum, and may be calculated as the sum of each lesion score measured in each organ (cecum, duodenum, and / or jejunum).

[0065] In one example, the amount of fecal oocysts shed can be measured by collecting feces shed from an individual and using a microscope or a counting chamber (e.g., a McMaster chamber).

[0066] In one example, the mortality rate may refer to the mortality rate of animals in which coccidiosis was induced, and a post-mortem examination may be performed to exclude the number of animals that died from causes other than coccidiosis.

[0067] In one example, an individual with induced coccidiosis may lose weight compared to an individual without induced coccidiosis, and the composition according to one example may inhibit weight loss due to induced coccidiosis.

[0068] In one example, the anticoccidial composite index can be calculated using the following mathematical formula 1, and the lesion score in mathematical formula 1 can be calculated using the method described above.

[0069] (Equation 1)

[0070] Anticoccidial composite index (ACI) = (Survival rate after challenge vaccination (%)) + (Daily weight gain compared to the negative control group (%)) - (Lesion score × 10) - (Fecal oocyst excretion index)

[0071] The above challenge inoculation may refer to the administration of a protozoan capable of inducing coccidiosis (e.g., oral inoculation, etc.). In one example, the survival rate may be a 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, and the survival rate may be measured by excluding the number of individuals that died from causes other than coccidiosis by performing a postmortem.

[0072] In the above mathematical expression 1, the weight gain compared to the negative control group may be a value calculated as a percentage based on the value of the negative control group (e.g., a negative control group not infected with protozoa).

[0073] The lesion score in the above mathematical expression 1 is as described above.

[0074] In the above mathematical expression 1, the fecal oocyst excretion index may be a numerical value calculated as a percentage based on the value of a negative control group (e.g., a negative control group infected with protozoa), and if the calculated result is 0% or more but less than 1%, 5% or more but less than 26%, 10% or more but less than 51%, 20% or more but less than 76%, and 40% or more but less than 100%.

[0075]

[0076] In one example, the effective ingredient (quinic acid or its salt) is present in the feed composition at 2 w / w% or less, 1 w / w% or less, less than 1 w / w%, or 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 1 w / w%, 10 -7 10 inland -1 w / w%, 10 -7 5 × 10 -2 w / w%, 10 -7 10 inland -2 w / w%, 10 -7 5 × 10 -3 w / w%, 10 -7 4 × 10 -3 w / w%, 10 -7 10 inland -3 w / w%, 10 -7 5 × 10 -4 w / w%, 10 -7 10 inland -4 w / w%, 10 -7 10 inland -5 w / w%, 10 -6 1 w / w%, 10 -6 10 inland -1 w / w%, 10 -6 5 × 10 -2w / w%, 10 -6 10 inland -2 w / w%, 10 -6 5 × 10 -3 w / w%, 10 -6 4 × 10 -3 w / w%, 10 -6 10 inland -3 w / w%, 10 -6 5 × 10 -4 w / w%, 10 -6 10 inland -4 w / w%, 10 -6 10 inland -5 w / w%, 10 -5 1 w / w%, 10 -5 10 inland -1 w / w%, 10 -5 5 × 10 -2 w / w%, 10 -5 10 inland -2 w / w%, 10 -5 5 × 10 -3 w / w%, 10 -5 4 × 10 -3 w / w%, 10 -5 10 inland -3 w / w%, 10 -5 5 × 10 -4 w / w%, 10 -5 10 inland -4 w / w%, 10 -4 1 w / w%, 10 -4 10 inland -1 w / w%, 10 -4 5 × 10 -2 w / w%, 10 -4 10 inland -2 w / w%, 10 -4 5 × 10 -3 w / w%, 10 -4 4 × 10 -3 w / w%, 10 -4 10 inland -3 w / w%, 10 -4 5 × 10 -4 w / w%, 10 -3 1 w / w%, 10 -310 inland -1 w / w%, 10 -3 5 × 10 -2 w / w%, 10 -3 10 inland -2 w / w%, 10 -3 5 × 10 -3 w / w%, 10 -3 4 × 10 -3 w / w%, 10 -3 2 × 10 -3 w / w%, or 10 -3 1.5 × 10 -3 It may be included in w / w%. In one example, the feed composition may be a feed (e.g., compound feed and / or single feed ultimately consumed by an animal) that includes the effective ingredient in the above range based on the total weight.

[0077] In one example, the effective ingredient (quinic acid or a salt thereof) is present in the feed composition at 10,000 ppm or less, 5,000 ppm or less, 2,000 ppm or less, 1,000 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, 0.001 ppm or more, 0.01 ppm or more, 0.1 ppm or more, 1 ppm or more, 5 ppm or more, 10 ppm or more, 15 ppm or more, 20 ppm or more, 30 ppm or more, 40 ppm or more, 50 ppm or more, 0.001 to 2,000 ppm, 0.001 to 1500ppm, 0.001 to 1000ppm, 0.001 to 500ppm, 0.001 to 300ppm, 0.001 to 200ppm, 0.001 to 125ppm, 0.001 to 100ppm, 0.001 to 90ppm, 0.001 to 80ppm, 0.001 to 70ppm, 0.001 to 60ppm, 0.001 to 50ppm, 0.001 to 40ppm, 0.001 to 30ppm, 0.003 to 2000ppm, 0.003 to 1500ppm, 0.003 to 1000ppm, 0.003 to 500ppm, 0.003 to 300ppm, 0.003 to 200ppm, 0.003 to 125ppm, 0.003 to 100ppm, 0.003 to 90ppm, 0.003 to 80ppm, 0.003 to 70ppm, 0.003 to 60ppm, 0.003 to 50ppm, 0.003 to 40ppm, 0.003 to 30ppm, 0.01 to 2000ppm, 0.01 to 1500ppm, 0.01 to 1000ppm, 0.01 to 500ppm, 0.01 to 300ppm, 0.01 to 200ppm, 0.01 to 125ppm, 0.01 to 100ppm, 0.01 to 90ppm, 0.01 to 80ppm, 0.01 to 70ppm, 0.01 to 60ppm, 0.01 to 50ppm, 0.01 to 40ppm, 0.01 to 30ppm, 0.1 to 2000ppm, 0.1 to 1500ppm, 0.1 to 1000ppm, 0.1 to 500ppm, 0.1 to 300ppm, 0.1 to 200ppm, 0.1 to 125ppm, 0.1 to 100ppm, 0.1 to 90ppm, 0.1 to 80ppm, 0.1 to 70ppm, 0.1 to 60ppm, 0.1 to 50ppm, 0.1 to 40ppm, 0.1 to 30ppm, 1 to 2000ppm, 1 to 1500ppm, 1 to 1000ppm, 1 to 500ppm, 1 to 300ppm, 1 to 200ppm, 1 to 125ppm, 1 to 100ppm, 1 to 90ppm, 1 to 80ppm, 1 to 70ppm, 1 to 60ppm, 1 to 50ppm, 1 to 40ppm, 1 to 30ppm, 3 to 2000ppm, 3 to 1500ppm, 3 to 1000ppm, 3 to 500ppm, 3 to 300ppm, 3 to 200ppm, 3 to 125ppm, 3 to 100ppm, 3 to 90ppm, 3 to 80ppm, 3 to 70ppm, 3 to 60ppm, 3 to 50ppm, 3 to 40ppm, 3 to 30ppm, 5 to 2000ppm, 5 to 1500ppm, 5 to 1000ppm, 5 to 500ppm, 5 to 300ppm, 5 to 200ppm, 5 to 125ppm, 5 to 100ppm, 5 to 90ppm, 5 to 80ppm, 5 to 70ppm, 5 to 60ppm, 5 to 50ppm, 5 to 40ppm, 5 to 30ppm, 10 to 2000ppm, 10 to 1500ppm, 10 to 1000ppm, 10 to It may be included in a concentration of 500 ppm, 10 to 300 ppm, 10 to 200 ppm, 10 to 125 ppm, 10 to 100 ppm, 10 to 90 ppm, 10 to 80 ppm, 10 to 70 ppm, 10 to 60 ppm, 10 to 50 ppm, 10 to 40 ppm or 10 to 30 ppm.

[0078] In one example, the anticoccidial activity may be more excellent when the effective ingredient is included in the above range.

[0079]

[0080] In this application, "feed" may mean any natural or artificial diet, meal, etc., or components of such meal, intended for or suitable for eating, ingesting, and digesting by an animal. A feed composition according to an example may additionally include a concentrate feed and / or a special feed. The above-mentioned concentrated feed may be animal feed such as dried seeds and fruits including grains such as wheat, oats, and corn, bran including rice bran, wheat bran, and barley bran as by-products obtained by refining grains, sesame seeds, flax seeds, and coconut oil, sesame cakes as by-products obtained by extracting soybeans, sesame seeds, linseeds, and coconut oil, residual starch which is the main component of starch residue remaining after removing starch from sweet potatoes, potatoes, etc., fish meal, fish waste, fish soluble which is concentrated fresh liquid obtained from fish, meat meal, blood meal, feather meal, skim milk powder, dried whey which is the residue when manufacturing cheese from milk or casein from skim milk, yeast, chlorella, and / or seaweed.

[0081] A feed composition according to an example may refer to feed in a form that is ultimately consumed by an animal, a dietary supplement that can be mixed into the feed, and / or a feed additive. The dietary supplement may refer to a composition containing a preparation that provides a therapeutic agent or a digestive agent to an animal, and although it is not usually a source of calorie intake for the body, i.e., an energy source, it may refer to a composition that is consumed in addition to a normal animal feed. The feed additive may refer to a substance added to feed for various purposes, such as supplementing nutrients and preventing weight loss, increasing the digestibility and availability of fiber in feed, improving milk quality, preventing reproductive disorders and improving conception rates, and preventing summer heat stress. In one example, it may refer to a substance added for the purpose of preventing, improving, or treating coccidiosis.

[0082] In one example, the feed composition may be a feed additive, and when the feed additive according to one example is mixed into feed (e.g., compound feed and / or single feed to be finally consumed by an animal), the feed additive may be present in an amount of 0.001% (w / w) or more, 0.005% (w / w) or more, 0.01% (w / w) or more, 0.05% (w / w) or more, 0.1% (w / w) or more, 0.5% (w / w) or more, 1% (w / w) or less, 0.5% (w / w) or less, 0.1% (w / w) or less, 0.05% (w / w) or less, 0.01% (w / w) or less, 0.005% (w / w) or less, 0.001 to 1% (w / w), 0.001 to 0.5% (w / w), based on the total feed weight. 0.001 to 0.1% (w / w), 0.001 to 0.05% (w / w), 0.001 to 0.01% (w / w), 0.001 to 0.005% (w / w), 0.005 to 1% (w / w), 0.005 to 0.5% (w / w), 0.005 to 0.1% (w / w), 0.005 to 0.05% (w / w), 0.005 to 0.01% (w / w), 0.01 to 1% (w / w), 0.01 to 0.5% (w / w), 0.01 to 0.1% (w / w), 0.01 to 0.05% (w / w), 0.05 to 1% (w / w), 0.05 to It may be added at a weight of 0.5% (w / w), 0.05 to 0.1% (w / w), 0.1 to 1% (w / w), 0.1 to 0.5% (w / w), or 0.5 to 1% (w / w) and mixed with feed raw materials, supplementary feed, supplements, and / or other types of additives other than the effective ingredient according to one example.

[0083] The above feed composition may additionally include any suitable excipient or solvent such as water commonly used in feed compositions, and such excipient may be, for example, a preservative, a wetting agent, a dispersing agent, a suspending agent, a buffer, a stabilizer, or an isotonic agent, but is not limited thereto.

[0084]

[0085] A pharmaceutical composition according to an example may be used as a single agent, or may be manufactured and used as a combined preparation by additionally including a pharmaceutical composition known to have an approved coccidiosis prevention or treatment effect. The pharmaceutical composition may be formulated into a pharmaceutical unit dosage form by adding a pharmaceutically acceptable carrier, excipient, or diluent.

[0086] In the present application, "pharmaceutically acceptable" means not significantly irritating to a living organism and not inhibiting the biological activity and properties of the administered active substance. In one example, the pharmaceutical composition comprising a pharmaceutically acceptable carrier may have any one dosage form selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, oral solutions, emulsions, syrups, sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories.

[0087] The above pharmaceutical composition may be administered orally or parenterally in various dosage forms. When formulated, it may be prepared using commonly used fillers, bulking agents, binders, wetting agents, disintegrants, surfactants, and other diluents or excipients.

[0088] Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations can be prepared by mixing one or more compounds with at least one excipient, such as starch, calcium carbonate, sucrose, lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc can also be used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, syrups, etc., and in addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives can be included.

[0089] Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solutions and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases may include witepsol, macrogol, Tween 61, cocoa butter, laurin butter, and glycerogelatin.

[0090] In one example, the pharmaceutical composition may be formulated and used in various forms, such as oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, and injections of sterile injectable solutions, according to conventional methods according to each intended use, and may be administered orally or through various routes, including intravenous, intraperitoneal, subcutaneous, rectal, and topical administration.

[0091] In one example, the pharmaceutical composition may further include a carrier, excipient, or diluent, and examples of suitable carriers, excipients, or diluents that may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, amorphous cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil. In addition, the pharmaceutical composition may further include a filler, an anticoagulant, a lubricant, a wetting agent, a fragrance, an emulsifier, a preservative, and the like.

[0092] According to one example, the effective amount of the active ingredient (quinic acid or its salt) in the pharmaceutical composition may vary depending on the age, sex, and weight of the patient (subject), and is generally 0.0001 to 1 mg / kg, 0.0001 to 0.1 mg / kg, 0.0001 to 0.01 mg / kg, 0.0001 to 0.001 mg / kg, 0.001 to 1 mg / kg, 0.001 to 0.1 mg / kg, 0.001 to 0.01 mg / kg, 0.01 to 1 mg / kg, 0.01 to 0.1 mg / kg, 0.1 to 1 mg / kg, administered daily or every other day, or divided into 1 to 3 times a day. However, the dosage may vary depending on the route of administration, severity of the disease, gender, body weight, age, etc., and thus does not limit the scope of the present invention in any way. In one example, when the composition is administered intraperitoneally, it may be administered at a concentration of 0.001 to 1 mg / kg.

[0093] In one example, the dosage of the pharmaceutical composition may vary depending on the patient's weight, age, sex, health condition, diet, administration time, administration method, excretion rate, and severity of the disease.

[0094] In one example, the quinic acid or a pharmaceutically acceptable salt thereof is present in the pharmaceutical composition in an amount of 2 w / w% or less, 1 w / w% or less, less than 1 w / w%, or 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 1 w / w%, 10 -7 10 inland -1 w / w%, 10 -7 5 × 10 -2 w / w%, 10 -7 10 inland -2 w / w%, 10 -7 5 × 10 -3 w / w%, 10 -7 4 × 10 -3 w / w%, 10 -7 10 inland -3 w / w%, 10 -7 5 × 10 -4 w / w%, 10 -7 10 inland -4 w / w%, 10 -7 10 inland -5 w / w%, 10 -6 1 w / w%, 10 -6 10 inland -1 w / w%, 10 -6 5 × 10 -2 w / w%, 10 -6 10 inland -2 w / w%, 10 -6 5 × 10 -3 w / w%, 10 -6 4 × 10 -3 w / w%, 10 -6 10 inland -3 w / w%, 10 -6 5 × 10-4 w / w%, 10 -6 10 inland -4 w / w%, 10 -6 10 inland -5 w / w%, 10 -5 1 w / w%, 10 -5 10 inland -1 w / w%, 10 -5 5 × 10 -2 w / w%, 10 -5 10 inland -2 w / w%, 10 -5 5 × 10 -3 w / w%, 10 -5 4 × 10 -3 w / w%, 10 -5 10 inland -3 w / w%, 10 -5 5 × 10 -4 w / w%, 10 -5 10 inland -4 w / w%, 10 -4 1 w / w%, 10 -4 10 inland -1 w / w%, 10 -4 5 × 10 -2 w / w%, 10 -4 10 inland -2 w / w%, 10 -4 5 × 10 -3 w / w%, 10 -4 4 × 10 -3 w / w%, 10 -4 10 inland -3 w / w%, 10 -4 5 × 10 -4 w / w%, 10 -3 1 w / w%, 10 -3 10 inland -1 w / w%, 10 -3 5 × 10 -2 w / w%, 10 -3 10 inland -2 w / w%, 10 -3 5 × 10 -3 w / w%, 10 -3 4 × 10 -3 w / w%, 10-3 2 × 10 -3 w / w%, or 10 -3 1.5 × 10 -3 It can be included as w / w%.

[0095] In one example, the composition may be administered in a pharmaceutically effective amount. In the present application, the term "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment, and the effective dosage level may be determined based on the type and severity of the patient's disease, the activity and sensitivity of the drug to the drug, the time of administration, the route of administration and the excretion rate, the duration of treatment, concomitant drugs, and other factors well known in the medical field. In one example, the composition may be administered as an individual treatment or in combination with other anticoccidial agents, and may be administered simultaneously, separately, or sequentially with conventional treatments, and may be administered singly or in multiple doses. It is important to administer an amount that can achieve the maximum effect with the minimum amount without causing side effects by taking all of the above factors into consideration, and this can be easily determined by those skilled in the art.

[0096] In one example, the quinic acid or a pharmaceutically acceptable salt thereof is present in the pharmaceutical composition at 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, 0.001 ppm or more, 0.01 ppm or more, 0.1 ppm or more, 1 ppm or more, 5 ppm or more, 10 ppm or more, 15 ppm or more, 20 ppm or more, 30 ppm or more, 40 ppm or more, 50 ppm or more, 0.001 to 2000ppm, 0.001 to 1500ppm, 0.001 to 1000ppm, 0.001 to 500ppm, 0.001 to 300ppm, 0.001 to 200ppm, 0.001 to 125ppm, 0.001 to 100ppm, 0.001 to 90ppm, 0.001 to 80ppm, 0.001 to 70ppm, 0.001 to 60ppm, 0.001 to 50ppm, 0.001 to 40ppm, 0.001 to 30ppm, 0.003 to 2000ppm, 0.003 to 1500ppm, 0.003 to 1000ppm, 0.003 to 500ppm, 0.003 to 300ppm, 0.003 to 200ppm, 0.003 to 125ppm, 0.003 to 100ppm, 0.003 to 90ppm, 0.003 to 80ppm, 0.003 to 70ppm, 0.003 to 60ppm, 0.003 to 50ppm, 0.003 to 40ppm, 0.003 to 30ppm, 0.01 to 2000ppm, 0.01 to 1500ppm, 0.01 to 1000ppm, 0.01 to 500ppm, 0.01 to 300ppm, 0.01 to 200ppm, 0.01 to 125 ppm, 0.01 to 100 ppm, 0.01 to 90 ppm, 0.01 to 80 ppm, 0.01 to 70ppm, 0.01 to 60ppm, 0.01 to 50ppm, 0.01 to 40ppm, 0.01 to 30ppm, 0.1 to 2000ppm, 0.1 to 1500ppm, 0.1 to 1000ppm, 0.1 to 500ppm, 0.1 to 300ppm, 0.1 to 200ppm, 0.1 to 125ppm, 0.1 to 100ppm, 0.1 to 90ppm, 0.1 to 80ppm, 0.1 to 70ppm, 0.1 to 60ppm, 0.1 to 50ppm, 0.1 to 40ppm, 0.1 to 30ppm, 1 to 2000ppm, 1 to 1500ppm, 1 to 1000ppm, 1 to 500ppm, 1 to 300ppm, 1 to 200ppm, 1 to 125ppm, 1 to 100ppm, 1 to 90ppm, 1 to 80ppm, 1 to 70ppm, 1 to 60ppm, 1 to 50ppm, 1 to 40ppm, 1 to 30ppm, 3 to 2000ppm, 3 to 1500ppm, 3 to 1000ppm, 3 to 500ppm, 3 to 300ppm, 3 to 200ppm, 3 to 125ppm, 3 to 100ppm, 3 to 90ppm, 3 to 80ppm, 3 to 70ppm, 3 to 60ppm, 3 to 50ppm, 3 to 40ppm, 3 to 30ppm, 5 to 2000ppm, 5 to 1500ppm, 5 to 1000ppm, 5 to 500ppm, 5 to 300ppm, 5 to 200ppm, 5 to 125ppm, 5 to 100ppm, 5 to 90ppm, 5 to 80ppm, 5 to 70ppm, 5 to 60ppm, 5 to 50ppm, 5 to 40ppm, 5 to 30ppm, 10 to 2000ppm, 10 to 1500ppm, 10 to 1000ppm, 10 to It may be included in a concentration of 500 ppm, 10 to 300 ppm, 10 to 200 ppm, 10 to 125 ppm, 10 to 100 ppm, 10 to 90 ppm, 10 to 80 ppm, 10 to 70 ppm, 10 to 60 ppm, 10 to 50 ppm, 10 to 40 ppm or 10 to 30 ppm.

[0097] In one example, the pharmaceutical composition may be administered to a subject via various routes. Administration may refer to providing a given substance to a subject (patient) by any suitable method, and the route of administration of the pharmaceutical composition may be oral and / or parenteral, as long as it can reach the target tissue. Parenteral administration may include topical application to the skin, intraperitoneal injection, intrarectal injection, subcutaneous injection, intravenous injection, intramuscular injection, and / or intrathoracic injection. Furthermore, the composition according to one example may be administered using any device capable of delivering the active ingredient to target cells.

[0098] In one example, the subject to which the composition or method is applied means an animal that has developed or can develop coccidiosis, and the animal may be a mammal including a human, a horse, a cow, a mouse, a rat, a dog, a cat, etc., a bird including a poultry (e.g., a breeding chicken, a broiler, and / or a laying hens), a fish, an amphibian, and / or a reptile.

[0099] In one example, the animal to which the composition or method is applied may be at least one selected from the group consisting of animals described in Table 1, and may be, for example, at least one selected from the group consisting of humans, chickens, ducks, geese, turkeys, quails, pheasants, pigeons, parrots, cattle, pigs, goats, sheep, horses, antelopes, oryxes, monkeys, cats, dogs, mice, rats, rabbits, raccoons, squirrels, bats, guinea pigs, camels, lizards, alpacas, wombats, lizards, goldfish, carp, tilapia, barbels, lungfish, and European chub. In one example, the animal may be an animal other than a human.

[0100]

[0101] Another aspect provides an antiprotozoal composition for protozoa of the genus Aemeria comprising quinic acid and / or a salt thereof.

[0102] Another aspect provides the use of quinic acid and / or its salts for the preparation of an antiprotozoal composition against protozoa of the genus Eimeria.

[0103] Another aspect provides a method for controlling protozoa of the genus Eimeria, comprising administering quinic acid and / or a salt thereof to a subject in need of control of protozoa of the genus Eimeria.

[0104] As for the protozoa of the genus Quinos and Aemeria, the same is as described above.

[0105] The above-mentioned antigen-containing composition may additionally include any suitable excipient or solvent such as water commonly used in antigen-containing compositions, and such excipient may be, for example, a preservative, a wetting agent, a dispersing agent, a suspending agent, a buffer, a stabilizer, or an isotonic agent, but is not limited thereto.

[0106]

[0107] In one example, superior antiprotozoal activity (effect, efficacy) against the protozoan of the genus Aemeria may mean the following characteristics (1) and / or (2), and for example, may mean exhibiting the following characteristics (1) and / or (2) compared to a control group (negative control group and / or positive control group):

[0108] (1) Excellent effect in killing protozoa of the genus Aimeria; and / or

[0109] (2) Inhibition of the cell penetration effect of the protozoan of the genus Aemeria and / or the proliferation effect of the protozoan within the cell.

[0110] In one example, the quinic acid or its salt may be included in the antiprotozoal composition in the concentration range described above in the feed composition and / or pharmaceutical composition.

[0111]

[0112] Another aspect provides a feed additive comprising an antigenic composition for the protozoa of the genus Aemeria.

[0113] Another aspect provides a feed comprising the above feed additive.

[0114] The above feed can be manufactured by separately manufacturing the above antigen-containing composition in the form of a feed additive and mixing it into the feed, or by directly adding it during the manufacture of the feed.

[0115] The anti-protozoal composition in the feed may be in a liquid or dry state, for example, may be in the form of a dried powder. The anti-protozoal composition may be included in an amount of 0.005 to 10 wt%, 0.05 to 10 wt%, 0.1 to 10 wt%, 0.005 to 5 wt%, 0.05 to 5 wt%, 0.1 to 5 wt%, 0.005 to 2 wt%, 0.05 to 2 wt%, or 0.1 to 2 wt% of the total feed weight, but is not limited thereto. In addition, the feed may further include conventional additives that can increase the preservative properties of the feed in addition to the anti-protozoal composition.

[0116] In the present specification, the feed to which the anti-protozoal composition can be added may be selected from the group consisting of commercially available feed, grains, roots, fruits, food processing by-products, algae, fibers, pharmaceutical by-products, oils, starches, meal, grain by-products, proteins, inorganic substances, oils, minerals, single-cell proteins, animal plankton, leftover food, etc., but is not limited thereto.

[0117] Another example provides a food additive or drinking water additive containing the above-described antiprotozoal composition as an active ingredient. By mixing the above-described antiprotozoal composition into drinking water and supplying it, the number of protozoa of the genus Aemeria in the drinking water can be reduced. The protozoa of the genus Aemeria are as described above.

[0118]

[0119] Another aspect provides a disinfectant comprising the above-described anti-protozoal composition.

[0120] Another aspect provides a disinfection method, comprising the step of applying the above-mentioned anti-protozoal composition to an object requiring disinfection. The disinfectant is a general term for agents capable of controlling protozoa of the genus Aemeria, and can be used as a general household disinfectant, a disinfectant for food and cooking facilities and equipment, and the disinfection of various livestock products such as buildings, livestock bodies, drinking water, bedding, egg trays, transport vehicles, and tableware.

[0121] Another aspect provides a detergent comprising the above-described antigen composition.

[0122] Another aspect provides a washing method comprising the step of applying the above-mentioned anti-protozoal composition to a subject requiring washing of protozoa of the genus Eimeria.

[0123] Since the above-mentioned anti-protozoal composition has a killing effect on protozoa of the genus Aemeria, it can be applied for the purpose of washing (cleaning) the skin surface or various parts of the body of an individual exposed or likely to be exposed to protozoa of the genus Aemeria.

[0124]

[0125] The present application relates to a composition for preventing, improving or treating coccidiosis containing quinic acid and an antiprotozoal composition against protozoa of the genus Eimeria, which has an excellent killing effect against protozoa of the genus Eimeria.

[0126]

[0127] Figure 1 is a graph showing the results of treating Eimeria tenella parasites with various concentrations of quinic acid and measuring the mortality rate of the parasites.

[0128]

[0129] The present invention will be described in more detail below with reference to the following examples. However, these examples are provided solely to illustrate the present invention, and the scope of the present invention is not limited by these examples.

[0130]

[0131] Example 1. Direct killing effect on Eimeria parasites

[0132] A certain amount of oocysts (parasite eggs) of Eimeria tenella and Eimeria maxima (Veterinary Medicine College, Gyeongsang National University, Republic of Korea) were placed in a tube containing glass beads and crushed. To remove the crushed oocyst cell walls and other debris, the internal sporocysts were purified using the Percoll density gradient and washed with phosphate buffered saline (PBS). To excyst the internal sporozoites, the sporocysts of Eimeria tenella and Eimeria maxima were treated with a reagent containing sodium taurocholic acid (Sigma Aldirich, USA) and trypsin (Ginco, USA), respectively, and incubated. After washing once with phosphate-buffered saline (PBS), the protozoa were obtained.

[0133]

[0134] Example 1-1. Direct parasite killing effect of quinic acid at different concentrations

[0135] Quinic acid (Sigma, Cas No. 77-95-2) was reacted with Eimeria tenella larvae at concentrations of 0 to 1000 ppm at 40°C for 3 hours, and only live protozoa (sporozoites) were counted through microscopic observation. At this time, the mortality rate (%) of protozoa was measured for each material treatment compared to the negative control group treated with PBS. The results are shown in Fig. 1 and Table 2, and the anticoccidial efficacy of quinic acid was confirmed depending on the concentration.

[0136]

[0137]

[0138] Quinic acid content (ppm) 1000 500 250 100 50 25 12.5 6.2 5 3.1 2 5 1.5 6 0.7 8 Larval mortality rate 100.0% 97.9% 91.5% 59.6% 55.3% 35.1% 31.9% 25.5% 20.2% 14.9% 7.4%

[0139] Example 1-2. Comparison of efficacy among chlorogenic acid components

[0140] The killing effects of quinic acid (sigma, Cas No. 77-95-2), chlorogenic acid (sigma, Cas No. 327-97-9), m-coumaric acid (sigma, Cas No. 14755-02-3), caffeic acid (sigma, Cas No. 331-39-5), and ferulic acid (sigma, Cas No. 1135-24-6) on protozoa of the genus Eimeria were confirmed.

[0141]

[0142] The larvae of Eimeria tenella and Eimeria maxima were reacted with 10 ppm concentrations of 0.1% (v / v) DMSO, quinic acid, chlorogenic acid, m-coumaric acid, caffeic acid, and ferulic acid, respectively, at 40°C for 3 hours, and only the live protozoa (sporozoites) were counted through microscopic observation. At this time, the mortality rate (%) of the larvae was measured for each material treatment compared to the negative control group treated with PBS, and the results are shown in Table 3 below.

[0143] sampleDose (ppm)Eimeria tenellasporozites mortality rate [Killed sporozoites %]Eimeria maximasporozites mortality rate [Killed sporozoites %]Cell only (PBS treatment, negative control)-000.1% DMSO-00Quinic acid103234Chlorogenic acid1000m-coumaric acid1010.76.4Caffeic acid1000Ferulic acid1000

[0144] As shown in Table 3 above, at the same concentration (10 ppm), quinic acid showed a superior direct killing effect on Eimeria tenella and Eimeria maxima parasites than chlorogenic acid, m-coumaric acid, caffeic acid, and ferulic acid.

[0145]

[0146] In addition, each material was treated at a concentration of up to 1000 ppm to kill the Eimeria tenella parasite, and the minimum treatment concentration for each material that showed a kill rate of 50% or more against the Eimeria tenella parasite is shown in Table 4 below.

[0147] sampleMinimum Dose for killed 50% sporozoite (ppm)Quinic acid50Chlorogenic acid500m-coumaric acid500Caffeic acidxFerulic acidx

[0148] As shown in Table 4 above, the minimum concentration that showed a 50% or higher killing rate against the Eimeria tenella parasite was lower for quinic acid than for chlorogenic acid, m-coumaric acid, caffeic acid, and ferulic acid, confirming that quinic acid has a significantly superior killing effect against the Eimeria tenella parasite.

[0149]

[0150] Example 1-3. Comparison of efficacy among chlorogenic acid families

[0151] The killing effect of Quinic acid (Sigma, Cas No. 77-95-2), Chlorogenic acid (Sigma, Cas No. 327-97-9), Theogallin (3-galloylquinic acid, Sigma, Cas No. 17365-11-6), and Cryptochlorogenic acid (Sigma, Cas No. 905-99-7) on protozoa of the genus Eimeria was confirmed.

[0152]

[0153] 0.1% (v / v) DMSO, quinic acid, chlorogenic acid, theogallin, and cryptochlorogenic acid were each reacted with Eimeria tenella parasites at a concentration of 10 ppm at 40°C for 3 hours, and only live parasites (sporozoites) were counted through microscopic observation. At this time, the mortality rate (%) of parasites treated with each material was measured compared to the negative control group treated with PBS, and the results are shown in Table 5 below.

[0154] sampleDose (ppm)Eimeria tenellasporozites mortality rate [Killed sporozoites %]Cell only (PBS treatment, negative control)-00.1% DMSO-0Quinic acid1032Chlorogenic acid100Theogallin100Cryptochlorogenic acid100

[0155] As shown in Table 5 above, at the same concentration (10 ppm), quinic acid showed a superior direct killing effect on Eimeria tenella parasites than chlorogenic acid, theogallin, and cryptochlorogenic acid.

[0156]

[0157] Example 1-4. Comparison of efficacy with sugarcane extract

[0158] The killing effects of quinic acid and sugarcane extracts against Eimeria parasites were investigated. Sugarcane from China, Vietnam, and Brazil was used, and sugarcane extracts extracted using water, methanol, and an organic solvent (a 3:1:1 volume mixture of methanol: water: chloroform) were used.

[0159]

[0160] Treatment with quinic acid or sugarcane extract at concentrations up to 1000 ppm kills Eimeria tenella parasites, and the minimum treatment concentration that causes a 50% or greater mortality rate against Eimeria tenella parasites is shown in Table 6 below.

[0161] sampleCountry of originExtraction methodMinimum Dose for killed 50% sporozoites(ppm)Quinic acid--50Sugar cane extractChinawaterXSugar cane extractChinamethanolXSugar cane extractChina3:1:1 mixture of methanol / water / CHCl3 (by volume)XSugar cane extractVietnamwaterXSugar cane extractVietnammethanolXSugar cane extractVietnam3:1:1 mixture of methanol / water / CHCl3 (by volume)XSugar cane extractBrazilwaterXSugar cane extractBrazilmethanolXSugar cane extractBrazil3:1:1 mixture of methanol / water / CHCl3 (by volume)X

[0162] As shown in Table 6 above, sugarcane extracts obtained from various origins and extraction methods did not show any killing effect against the Eimeria tenella parasite even at concentrations up to 1000 ppm, confirming that quinic acid has a significantly superior killing effect against the Eimeria tenella parasite.

[0163]

[0164] From the above description, those skilled in the art will understand that the present invention can be implemented in other specific forms without altering its technical spirit or essential characteristics. In this regard, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. The scope of the present invention should be interpreted as encompassing all changes or modifications derived from the meaning and scope of the following claims and their equivalent concepts, rather than the detailed description above.

Claims

1. A feed composition for preventing or improving coccidiosis, comprising quinic acid or a salt thereof as an active ingredient.

2. A feed composition according to claim 1, wherein the coccidiosis is induced by a protozoan of the genus Eimeria (Eimeriasp.).

3. A feed composition in the second paragraph, wherein the protozoan of the genus Eimeria is Eimeria tenella or Eimeria maxima.

4. In the first paragraph, the feed composition is a feed composition containing the effective ingredient at a concentration of 1% (w / w) or less based on the total weight.

5. A feed composition according to any one of claims 1 to 4, wherein the feed composition is a feed additive.

6. A pharmaceutical composition for preventing or treating coccidiosis, comprising quinic acid or a salt thereof as an active ingredient.

7. A pharmaceutical composition according to claim 6, wherein the coccidiosis is induced by a protozoan of the genus Eimeria (Eimeriasp.).

8. A pharmaceutical composition according to claim 7, wherein the protozoan of the genus Eimeria is Eimeria tenella or Eimeria maxima.

9. An antiprotozoal composition against protozoa of the genus Aemeria, comprising quinic acid or a salt thereof as an active ingredient.

10. An anti-protozoal composition according to claim 9, wherein the protozoan of the genus Eimeria is Eimeria tenella or Eimeria maxima.

11. A feed additive comprising the antigen-containing composition of claim 9 or 10.

12. A disinfectant comprising the anti-protozoal composition of claim 9 or 10.

13. A detergent comprising the anti-protozoal composition of claim 9 or 10.

14. A method for preventing, improving, or treating coccidiosis, comprising administering to an animal other than a human a composition selected from the group consisting of a feed composition according to any one of claims 1 to 4, a pharmaceutical composition according to any one of claims 6 to 8, and an antiprotozoal composition according to claim 9 or 10.

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