Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
  • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K10/00—Animal feeding-stuffs
  • A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K20/00—Accessory food factors for animal feeding-stuffs
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K20/00—Accessory food factors for animal feeding-stuffs
  • A23K20/10—Organic substances
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K20/00—Accessory food factors for animal feeding-stuffs
  • A23K20/10—Organic substances
  • A23K20/163—Sugars; Polysaccharides
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K20/00—Accessory food factors for animal feeding-stuffs
  • A23K20/10—Organic substances
  • A23K20/195—Antibiotics
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K50/00—Feeding-stuffs specially adapted for particular animals
  • A23K50/70—Feeding-stuffs specially adapted for particular animals for birds
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K50/00—Feeding-stuffs specially adapted for particular animals
  • A23K50/70—Feeding-stuffs specially adapted for particular animals for birds
  • A23K50/75—Feeding-stuffs specially adapted for particular animals for birds for poultry
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K50/00—Feeding-stuffs specially adapted for particular animals
  • A23K50/80—Feeding-stuffs specially adapted for particular animals for aquatic animals, e.g. fish, crustaceans or molluscs
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
  • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
  • A61K31/7032—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P33/00—Antiparasitic agents
  • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
  • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
  • A23V2200/00—Function of food ingredients
  • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
  • A23V2200/32—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the digestive tract

Definitions

• the present Invention relates generally to prevention, inhibition and treatment of
• coccidiosis and more specifically to plants and phytochemicals for anii-coccidiosis.
• Coccidiosis may be a major parasitic disease of . poultry and causes a considerable economic loss in the poultry industry.
• the loss due to coccidiosis includes mortality, malabsorption, inefficient feed utilization, and impaired growth rate in broilers and. a temporary reduction of egg production in layers, it was estimated that coccidiosis in the poultry industry in Great Britain caused a yearly loss of 61 millio USD. By extrapolation, the global costs could be expected to be 2400 millio USD per annum.
• Eimeria a Coccidia subclass
• the genus Eimeria belongs to spore-forming, unicellular, and obligate protozoa. That is to say, they must live and reproduce within animal cells.
• Eimeria is an intestinal parasite arid can infect .fishes, reptiles, birds, mammals.
• chickens are susceptible to at least 1 1 species of Eimeria.
• E, te li , E, mcatrix, E. bnmetti and E. maxima are the more virulent species and E. ac rvulma, E. praecox and E, mi lis are less virulent species in chickens.
• Eimeria infection is usually asymptomatic and however, shows severe clinical symptoms such, as diarrhea, bloody droppings, dehydration, droopiness, listlessness, loss of appetite, paleness, ruffled feathers and huddling in young and immune-compromised animals.
• the life cycle of Eimeria comprises intracellular, extracellular, asexual, and sexual stages.
• the parasites develop in the chicken and give rise to a microscopic egg (called an oocyst) which is passed out in the droppings.
• an oocyst develops within one to two days to form a sporulated oocyst which is capable of infecting other chickens.
• the ooc st contains eight bodies (called porozoites), each of which is c apabl e of enter ing a cell in the chicken's intestine after th e oocyst is eaten.
• sporozoites When sporozoites enter the cells, they divide many times producing either a few or many offspring (merozoites). The numbers produced depend cm the species of coccidia involved . Each merozoite in turn may enter another intestinal cell. This cycle ma be repeated several times.
• microgametocyte Because of this cyclic multiplication, large numbers of intestinal cells are destroyed. Eventually, the cycle stops and sex cells (microgametocyte and macrogametocyte) are produced. Microgametocyte
• Vaccination and chemotherapeutie approach are currently used to prevent and treat coccidiosis.
• Live attenuated vaccines are used to prevent coccidiai infection.
• Its advantage is lack of residual antibiotics in the chicken meat.
• the cross-species protection in coccidian vaccines is unsatisfactory.
• the most widely used compounds are the ionophore antibiotics, monensin, narasin, salinoroyein, maduramicin, se duramicin and lasalocid, which prevent the development of first generation sehizonis of the Elmeria genus.
• antibiotic-resistant Eimeria strains ha ve recently been isolated. Moreo ver, the residual antibiotics in.
• the invention relates to a composition for prevention, inhibition and/or treatment of coccidiosis in an animal in need thereof.
• the composition comprises an effective amount of Bidem piJosc an active constituent thereof or an active compound isolated therefrom.
• the invention relates to a composition for use in preventing and/or treating coccidiosis, and/or enhancing growth in an animal, the composition comprising an. animal feed and an effective amount of a compound comprising a polyacetylenic compound having a chemical structure of
• R? is monosaccharide
• the invention relates to a compositio comprising: f a) an animal feed; and (b) Bid m piiosa, an active constituent thereof, or an isolated compound comprising a
• R2 is monosaccharide
• 0 1 or 2: and in an effective amount for preventing and/or treating coccidiosis, and/or enhancing growth i an animal in need thereof.
• This invention is based on the unexpected finding that a naturally occurring polyacetylenic compound was effective in preventing and or treating coccidiosis, and/or promoting growt in a animal in need thereof.
• the polyacetylenic compound may be a pure compound of formula (I):
• R ⁇ is H, O-Cio aikyi, C2-C 1 0 alkenyl, C 2 -C10 alkynyl, C3-C20 cycloalk l, Cr C2 cycioalkenyL C1-C20 heterocycloaikyl, Cj-C 2 o heterocycioa!kenyl, aryl, or heieroaryl;
• R 2 is a monosaccharide residue;
• R.3 ⁇ 4 is H or O-Cio alkyl; ra is 2, 3, or 4; n is 0, 1 , 2, or 3; o is 0, 1 , 2, 3, or 4 and p is 1, 2, 3, of 4.
• pure compound 5 refers to a compound that has a purity of at least 80% (e.g., 95% or 99%).
• a subset of the polyacetylenic compounds described abo v e are those in which R3 ⁇ 4 is O-Cw alkyl (e.g., methyl), 3 ⁇ 4 is glyco ranose; is H or Cj-C. «, alkyl; m is 4; n is 0; o is 2; and is I .
• alkyl refers to a saturated, linear or branched, non-aromatic hydrocarbon moiet such as Cl3 ⁇ 4, or branched ( €Hjh €l3 ⁇ 4-.
• alkenyi refers to a linear or branched, non-aromatic hydrocarbon moiety having at least one double bond, such as CMj-CH-, or -CH ⁇ CH ⁇
• alkyny refers to a linear or branched, non-aromatic hydrocarbon moiety having a least one triple bond, such as CfteC- or -Cs -.
• cyc ' loalkyl refers to a saturated non-aromatic cyclic hydrocarbon moiety, such as cyclohexyL
• cycloalkenyi refers to a non-aromatic.
• cyclic hydrocarbon moiety thai contains at least one double bond in the ring, such as cyclohexenyl.
• 'lieterocycloaikyP * refers to a.
• heterocycloalkenyl refers to a non-aromatic, cyclic moiety having at least one ring heteroatom and at least one double bond in the ring, such as pyranyl.
• aryl refers to a hydrocarbon moiety having at least one aromatic ring. Examples of aryl moieties include phenyl, phenylene, foiphenyl, naphthyl, naphtliylene, pyrenyl, anthryl, and phenanthryl.
• heteroaryr refers to a moiety having at least one aromatic ring which contains at least one heteroatom.
• heteroaryi moieties include ftiryl, furylene, fluoreny!, pyrrol l, thienyl, oxa olyl, imidazoiyl. thiazolyl, pyridyl, pyrimidinyi, qistnazolinyi, isoquinolyl, and indolyl.
• Alkyl, alkenyi, alkynyl, cycloaikyi, cycloalkenyl, heterocyeloai yi, heterocycloalken l, aryl and heteroaryi mentioned herein include both substituted and imsuhstitifted moieties.
• substituerits on cycloaikyi, cycloalkenyl, heterocyeloaikyi, heterocycloalkenyl, aryl, and heteroaryi include, but are not limited to, CJ-CJO alkyl, Cs-Cuv alkenyi, C 3 ⁇ 4 -Cu> alkynyl, Cj-Cio cycloaikyi, Qj- C20 cycloalkenyl, Cj-Cu> alkoxy, aryl, arytoxy, heteroaryi, heteroaryi oxy, amino, O-Cio alkylamrao, C1-C20 dialkylamino, arylamino, diarylamino, heteroarylamino, diheteroarylami.no, Cj- Cio alkyisulfony, aryisulfonyl, heteroarylsulfonyl, Cr o alkylsulfonamide, arylsulfonamide, heteroary
• substituenis on alkyl, alkenyl, and aikynyl include all of the above- recited substituents except Ci ⁇ Oo alfc i C2.-O0 alkenyl, and C Cso aikynyl Cycloalkyl, cycloalkenyi, heterocycloalkyl, heterocycloalkenyl, ary , and heteroaryl can also be fused with each other.
• a subset of the polyacetylenk compounds are those in which 3 ⁇ 4 is CrCio alkyl (e.g., methyl); 3 ⁇ 4 is a glucose, galactose, fucose, mannose, gulose residue, or H; 3 ⁇ 4 is li; m is 4, n is 0, o is 2, and p is I .
• a po ' lyacet ienic compound may be administered to the subject as a pure compound in a pharmaceutical, compositio or as a component in a Bidem piiosa extract.
• this invention features a method for preventing and/or treating
• Bidem pitosa preparation can he obtained by stirring pulverized Bidem pilosa plants in water at an elevated temperature (e.g.. at 50°C or 1O0°C) to form a suspension, and collecting a supernatant of the suspension. The supernatant can be further extracted with an alcohol (e.g., n-butanol) to provide an enriched preparation.
• the Bidem pilosa preparation contains one or more of the polyacetylenk compounds of the just-mentioned formula (I). For example, it contains cytopiloyne:
• the polyacetylenk compounds described above include the compounds themselves, as well as their salts, prodrugs, and solvates, if applicable.
• Such salts for example, can be formed by interaction between a negatively charged substituent (e.g., carboxylate) on a polyacetylenk
• Suitable cations include, but are not limited to, sodium ion, potassium ion, magnesium ion, calcium, ion, and an ammonium cation (e.g., teiramethylam.nioftiu.rn ion ⁇ ..
• a positively charged substituent e.g., amino
• Suitable counterfoils include, but are not limited to, chloride, bromide, iodide, sulfate, nitrate, phosphate, or acetate.
• prodrugs include esters and other pharmaceutically acceptable derivatives, which, upon administration to a subject, are capable of providing above compounds described above.
• a solvate refers to a complex formed between a polyacetylenk compound and a pharmaceutically acceptable solvent.
• pharmaceutically acceptable solvents include water, eihanof isopropanoL n-butanoL ethyl acetate, and acetic acid.
• the poiyacef lenic compounds may contain one or more asymmetric centers or a non- aromatic double bond. Thus, they can occur as racemates and racemic mixtures, single
• compositions including a idens pilosa extract, containing one or more of the polyacetylenic compounds described above for use in preventing and/or treating coccidiosis, and/or promoting growth in an animal in. need thereof, and the use of such a composition for the manufacture of a medicament for the just-mentioned use.
• FIG. 1. shows preparation of B. pilosa powder and diet formulation. The photo of A 1 , pilosa
• FIG. 2. shows the effect of BPP on growth and feed conversion in the chickens.
• A One-d- old chickens had free access to water and feed (control diet, 5%, 10%, 15% and 20% BPP diet).
• A The body weight, of the birds and consumption of different diets were measured.
• B Food
• conversion ratio is obtained by the ratio of weight gain to the consumed diet.
• the number of the birds is indicated in the parentheses.
• F!Gs. 2C-D show the appearances and feces of chickens fed with the different BPP levels feed, in which the left side was control and right side was 5% BPP supplement in feed
• FIG. 3 shows the effect of BPP on the survival rate (FIG. 3A), sick bird appearance (FIG. 38) and clinical symptoms (FIG. 3C) in the chickens.
• One-day-old chickens were fed with control diet for 1 days.On day 14, the birds were infected with vehicle (CTR.) or E. tenetia (ET) and fed with control diet (CTR and ET groups) and the diet containing 6 mg kg maduramicm (ET + Mad), or 5 %, or 1 %, or 0.5% of BPP (ET + BPP) for additional 7 days.
• CTR. vehicle
• ET groups control diet
• EPP E. tenetia
• FIG. 4. shows the effect of cytopiloyne on the sick bird appearance and clinical symptoms in the chickens.
• One-day-old chickens were fed with control diet for 14 days.On day 14, the birds were infected with vehicle (CT ) or E. ienelia (ET) and fed with control diet (CI and ET groups) and the die containing 45 fi kg cytopiloyne (ET + CP) for additional 7 days.
• CT vehicle
• ET E. ienelia
• CI and ET groups control diet
• E + CP control diet
• the seik bird appearance (FIG. 4 A), bloody stool (FIG. 4B) and cecal pathology in low magnification power (PIG, 4C) and (FIG. 4D) in high magnification power were measured.
• FIG. 5 shows the effect of cytopiloyne on mucosal pathology in the chickens.
• Ceea of the same chickens from FIG. 4 were fixed with 10% formalin and embedded with patafin.
• FIG. 5A The sections were stained with hematoxylin and eosin Y.
• FIG. 5B- C The images of cecal slides were photographed and mucosal severity (FIG. 5B) and inflammation (FIG. 5C) were determined.
• FIG. 5D shows the chemical structure of cytopiloyne.
• Coccidiosis Coccidian parasites infect the intestinal tracts of animals, infection with these parasites is known as coccidiosis.
• Coccidiosis is a usually acute invasion and destruction of intestinal mucosa by protozoa of the -genera Eimeria or Isospara, Infection is characterized, by diarrhea, fever, inappetence, weight loss, emaciation, and sometimes death.
• Coccidiosis is a serious disease in cattle, sheep, goats, pigs, poultry, and also rabbits, in which the liver as well as the intestine can be affected. In dogs, cats, and horses, it is less often diagnosed but can result i clinical i l lness.
• Eimeria is a genus of Apicomplexan parasites that includes various species responsible for the poultry disease coccidiosis.
• Flam constituents or active ingredients are elements that have a marked, medical action upon the body .
• An animal feed refers to food given to domestic livestock, and pet (companion animal) food.
• pure compound used herein refers to a compound that has a purity of at least S0% (e.g., 95% or 99%).
• treating refers to administration of an effective amount of Bidem pihsa or its phytoc-hemicais (e.g., pofyacety!enic compounds such as cytopiloyne) to a subject, who has coccidosis, or a symptom or predisposition toward such a disease, with the purpose to cure, alleviate, relieve, remedy, ameliorate, or prevent coccidosis, the symptoms of it, or the
• an effective amount refers to an amount that may be therapeutically effective to enhance growth, and/or inhibit, prevent, or treat a symptom of a particular disease, disorder, condition, or side effect described herein.
• an effective amount may refer to the amount that is required to confer a therapeutic or a destred effect on the treated subject. Effective doses will van', as recognized by those skilled in the art, depending on route of administration, excipient usage, and the possibility of co-usage with other therapeutic treatment.
• the invention relates to the discovery of novel and safe ami-eoecidial compounds from the nature.
• the invention relates to the discovery of the effects ⁇ . pilosa on the growth and Eimeria infection in poultry such as chickens.
• B. pilosa powder was prepared first. Then chicken diets were formulated by mixing with different percentages of B. pilosa powder. The advantage of B. pilosa on growth performance in. chickens was tested. It was found that 10% or less of BPP enhanced growth and feed conversion, in chickens. The therapeutic effect of B. pilosa on coccidiosis in chickens was evaluated by survival rate. excreted, oocysts and gut lesions of the chickens, it was discovered thai BPP effectively reduced mortality, clmical symptoms and excreted oocysts following the Eimeria challenge. Overall, #. pilosa was demonstrated to be beneficial for chicken growth and therapeutically effective against coccidiosis in chickens. The data also suggest the potential of /?, pilosa to treat Eimeria infection. Polyacetylenic Compounds
• Polyacetylenic compounds e.g., cytopiloyne
• cytopiloyne can be isolated, from Bidens pilosa.
• Bidens pilosa plants are first pulverized and then stirred in heated water. After removal of insoluble materials (e.g., by filtration, decantaticm, or centrtftigation), the resultant supernatant is subjected to liquid chromatography (e.g., high-pressure liquid chromatography) or other suitable methods to afford pure polyacetylenic compounds.
• liquid chromatography e.g., high-pressure liquid chromatography
• the pure compounds thus obtained can be further derivatized to provide a number of other polyacetylenic compounds of this invention (US Patent No. 7,763,285. and Kusano et al (JP 2004083463), all of which are incorporated herein by reference in their entireties).
• polyacetylenic compounds described above can also be prepared by conventional methods. Below are three reaction schemes illustrating synthetic routes to a polyacetylenic compound of this invention.
• Butane- 1 ,2,4-triol (i) is reacted with acetone to form a protected 1,2,4-triol compound (ii), which can be readily transformed to an iodo derivative (in).
• Compound (Hi) is then reacted with ethywyltrimethylsilane, under a basic condition (e.g., n-BuLi), to give (4-(2,2-dimethyl-t ,3- dioxoiaB-4-yI ⁇ biit-l-yn 1)trimeth isilane (iv).
• Compound (iv) is subsequently treated with an acid (e.g., acetic acid), followed by a coupling reaction with 2-bromoglucopyranose to afford an adduct (v).
• Compound (v) can be further treated with potassium fluoride to afford 2 ⁇ phenyl-4H-chromen- 4-one (vi).
• Scheme 3 demonstrates a coupling reaction between an acetylene derivative ( ⁇ ), obtained from Scheme 1, and 1 -iodohepia- J ,3,5 ⁇ triyne (x), obtained from Scheme 2, to a tetrayne compound (xi). Removal of protecting groups affords a poJyacetylenic compound, 2p-D ⁇ g!iicop ranosy!oxy ⁇ l-hydroxyirideca-5,7,9,1 1 -tetrayne, a compound of this invention.
• This invention features a method of administrating an effective amount of one of the above- described polyacetylenic compounds or a Bidem pilosa preparaiion containing such a compound, to a subject in need thereof.
• a composition for oral administration can be any orally acceptable dosage form including, capsules, tablets, emulsions, and aqueous suspensions, dispersions, and solutions, in the case of tablets, commonly used carriers include lactose and corn starch. Lubricating agents, such as magnesium siearaie, are also typically added.
• useful diluents include lactose and dried corn starch.
• tely 10 kg of cleaned and crushed, plants, in their en ti rety was refluxed in 40 L of water for two hours. After removal of aqueous phase, insoluble materials was again refluxed in 25 L of water for two hours.
• the combined aqueous solutions (approximately 65 L) were evaporated in vacuo to yield a residue, which was subsequently suspended in 1.0 L of water and extracted with .! .0 L of « ⁇ butanol for three times.
• the « ⁇ butanol fraction was first evaporated on a vacuum rotary evaporator under reduced pressure and then lyopliiii ed to provide a crude product of cytopiloyne (37.7 g).
• the invention relates to a composition for use in prevention, inhibition and/or treatment of coccidiosis in an animal in need thereof, the composition comprising a effective amount of Bidem piiosa, an active constitiiem thereof, or an active compound isolated theref om.
• the invention in another aspect, relates t a composition for use in preventing and/or treating coccidiosis., and/or enhancing growtii in an animal in need thereof, the composition comprising an animal feed and an effective amount of a compound comprising a poly acetyl en ic compound having a chemical structure of
• i is H or Cffi
• R 2 is monosaccharide
• R 3 is H or COCHzCOOH
• the composition may be prepared by adding the Bidem pilosu, the acti ve constituent thereof, or the active compound isolated therefrom into an animal feed prior to the use.
• the composition may be in a dosage form selected from the group consisting of a oral dosage form, capsule dosage form, a suppository dosage form and a parenteral dosage form.
• the composition may further comprise an animal feed such as a chicken feed.
• the composition comprises the animal feed and 0.0005 % ⁇ 15% (w/w) of Bidem ptiosa (e.g.. Biden ptiosa powder).
• Bidem ptiosa e.g.. Biden ptiosa powder
• the Bidem ptiosa maybe in a form of powder.
• the active constituent or the acti ve compound isolated thereirom comprises a polyaeetylenk compound having a chemical structure of
• Rj is monosaccharide
• Rj is H or COCHjCOOH
• the polyaeetylenk compound may be selected from the group consisting of OGlc
• the animal is adminisiered the poiyacetyariac compound at a dose of no less than 45 itg kg body weight.
• the animal may be a non-human animal .
• the animal may be selected from the group consisting offish, birds, reptiles, and non-human mammals.
• the invention relates to a composition
• a composition comprising: (a) a animal feed; and (b) Bidem pi sc an active constituent thereof, or an isolated compound comprising a poiyacetyienic compound having a chemical structure of
• R.2 is monosaccharide
• R. is H COC3 ⁇ 4COOH; mTM3 or 4;
• the animal feed is selected from the group consisting of poultry feed, fish food, reptile food, bird feed, and non-human mamm l food.
• the animal feed may be a chicken feed.
• the compound may be isolated from the Bkiem pihsa.
• the composition compri ses the animal feed and cytopiloyne a t the ratio of 0.01 mg - 3 g of cytopiloyne per kilogram of the animal feed.
• the composition may comprise the animal feed and no more than 15 % (w w) of Bkiem pihsa and/or no !ess than 0.0005 % (w/w) ⁇ idem pihsa.
• the invention in another aspect, relates to a composition for preventing and/or treating coccidiosis, and/or promoting growth in a non-human animal in need thereof, the composition comprising an animal feed and an effective amount of Bkiem pihsa and/or an active compound isolated therefrom.
• the animal may be a .non-human animal suc as a chicken.
• the composition is also for use in causing an increase in the body weight and feed conversion in the chicken.
• the coccidiosis comprises Eimeri infection.
• the active compound comprises a chemical structure of
• the composition comprises the animal feed and no more than 15 % (w w), or no more than 10% (w/w) of Bidens pihsa and/or no less than 0.0005 % (w/w) of Bkiem pihsa.
• the composition may comprise the animal feed and Bidens pilosa in the range of 0.0005 % ⁇ 15 % (w/w), or 0.0005 % ⁇ 10% (w/w), or 0.0005 % - 5 % (w/w), or 0.0005 % ⁇ - i % (w/w), or in the range of 0.5 % ⁇ - ⁇ 5 % (w/w), or 0.5 % - 1 % (w w), or no more than 1 % (w/w).
• the animal may be administered Bkiens pilosa at. a dose ranging from 0.5 mg to 15,000 ffig/kg of bod weight.
• 0.0005 % ⁇ 15 % (w/w) it meant that all ten-thousandth, thousandth, hundredth, tenth and integer unit amounts within the range are specifically disclosed as part of the invention.
• 0.01 %, 0,02 %, 0,03 %. . , 0, 1 %, 0.2 %, 0.3 %, 0.4 %, 0,5 %, 0.6 %, 0,7 %, 0.8 %, 0.9 % and 1 %, 2 %, 3 % 5 4 % . . . 13 %, 14 %, and 5 % unit amounts are included as embodiments of this invention.
• the composition comprises an animal feed and cytopiloyne, wherein the ratio of cytopiloyne to the animal feed is 0.01 mg -- 3g of cytopiloyne per kilogram of the animal feed.
• the animal may be administered 0.00.1 mg - ⁇ 3 mg of cytopiloyne per kilogram body weight.
• 0.01 mg ⁇ 3g it meant that all hundredth, tenth and integer unit amounts within the range are specifically disclosed as part of the invention.
• 0.01 mg, 0.02 mg, 0.03 mg. . . 0.1 mg, 0.2 mg, 0.3 mg 0.998 g, 0.999 g, 1 g. . . 1.98 g : . 1.99 g, 2 g. . . 2,8 g, 2.9 g and 3 g unit amounts are included as embodiments of this invention.
• the animal may comprise a chicken having Eimeria infection.
• the aforementioned composition may also be used for causing a reduction in mortality,, clinical symptoms and excreted oocysts i the chicken.
• the aforementioned compound may comprise cytopiloyne.
• the invention relates to a composition
• a composition comprising: a) an animal feed; and b) Bidem pilosa or an isolated compound comprising a chemical structure of
• Ri is monosaccharide
• i H or COCHsCOOH
• the isolated compound may be chemically synthesized or isolated from Bidem pi sa.
• the isolated compound comprises a chemical structure of
• B. pilosa powder whole plant of & pilosa was harvested and washed. The plant was shade-dried for 3 days and grounded into powder (FIG. 1). The B, pilosa powder (BPP) was sieved with mesh and used as the material for the formulation.
• BPP diet was formulated by mixing the normal chicken diet (control diet) with the indicated amount of BPP (5%, 10%, 15% and 20% of total weight (the amount of normal diet and BPP),
• Table 2 shows body weight of the birds with or without Eimeria infection, One-d-old chickens were fed with control diet for 14 days. On day 14, the birds were infected with vehicle (CTR) or E. te lla (ET) and fed with control diet (CTR and ET groups) and the diet containing 6 rag/kg maduramicin (ET + Mad) or 50g/kg BPP (ET 4 * BPP) for additional 7 days. Body weight was measured. The number of the birds in each group is indicated in the parentheses.
• BPP treatment increased the number of villi and the depth of crypts in the gut of the birds infected with Eimeria (FIG, 3E).
• BPP reduced gut inflammation to a greater extent than maduramicin (FIG. 3E).
• BPP in feed is beneficial for the growth of chickens. More importantly, BPP can prevent and treat coccidiosis in chickens as evidenced by th ⁇ ; survival rate, sick bird appears rnce and clinical signs such as bloody droppings. diarrhea and gut lesions.
• FIG. 4 shows the effect of cytopiloyne on the sick bird appearance and clinical symptoms in the chickens.
• One-day-old chickens were fed with control diet for 14 days.Qn. day 14, the birds were infected with vehicle (CTR) or E. tenetta (ET) and fed with control diet (CTR and ET groups) and the diet containing 45 pg kg cytopiloyne (ET 4 * CP) for additional 7 days.
• CTR vehicle
• ET groups control diet
• E 4 * CP 45 pg kg cytopiloyne
• FIG. 5 shows the Effect of cytopiloyne on mucosal, pathology in the chickens.
• Ceca of the same chickens from FIG. 4 were fixed with 10% formalin and embedded with parafin.
• FIG. 5 A The sections were stained with hematoxylin and eosm Y, (FlGs. 5B ⁇ C).
• the images of cecal slides were photographed and mucosal severity (FIG. B) and inflammation (FIG. 5C) were determined.
• FIG. 5D shows the chemical structure of cytopiloyne.
• animals are administered a composition comprising an effective amount of Bkiens piiosa, an active constituent thereof, or an active compound isolated therefrom, Bkiens piiosa, an active constituent thereof, or an active compound isolated therefrom may be added to the animal feed.
• the active constituent or active compound of Bkiens piiosa may be extracted from the plant Bidem piiosa.
• Bidens piiosa powder, an active constituent thereof, or an active compound isolated therefrom may be prepared in a form of a capsule.
• the composition may be prepared in a
• a pharmaceutically acceptable carrier may be added for preparing

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• 2012
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