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CN111067950A - Novel veterinary anthelmintic compound and preparation method and application thereof - Google Patents

Novel veterinary anthelmintic compound and preparation method and application thereof Download PDF

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CN111067950A
CN111067950A CN202010053288.4A CN202010053288A CN111067950A CN 111067950 A CN111067950 A CN 111067950A CN 202010053288 A CN202010053288 A CN 202010053288A CN 111067950 A CN111067950 A CN 111067950A
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species
extract
bud
reduced pressure
agrimony
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董小雪
董丽平
李玉斌
闫爱青
申姗姗
王安妮
邵欣欣
祁悦
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    • 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)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/5545—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having eight-membered rings not containing additional condensed or non-condensed nitrogen-containing 3-7 membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps

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Abstract

The invention relates to a novel veterinary anthelmintic compound and a preparation method and application thereof. The preparation method comprises reflux-extracting fresh or dried herba et Gemma Agrimoniae bud with water or ethanol, concentrating under reduced pressure to obtain soft extract, and drying. The prepared agrimony bud extract has good insect expelling activity.

Description

Novel veterinary anthelmintic compound and preparation method and application thereof
Technical Field
The invention relates to the field of medicine extraction, in particular to a novel veterinary anthelmintic compound and a preparation method and application thereof.
Background
Agrimonia pilosa bud (Gemma Agrimoniae), which is named as radix Euphorbiae Fischerianae, semen Euphorbiae Fischerianae, and herba et Gemma Agrimoniae root bud. Perennial herb of Rosaceae, dried winter bud (underground rhizome bud) with short rhizome. Perennial herbs with a height of 30-120 cm. Odd feathered compound leaves are alternate, the supporting leaves are sickle-shaped, thin egg-shaped, the tip is sharp or tapered, the edge is provided with sharp saw teeth or splinters, and the thin whole edge is provided; the leaflets are 2 in size, alternate on the leaf axis, 3-4 pairs of larger leaflets and 2 pairs of thinner leaflets are grown on the leaf axis, the number of the leaflets is reduced to 3 leaflets, the leaflets are almost without stems, the leaflets are in a shape of inverted oval to inverted oval and are needle-shaped, the length of the leaflets is 1.5-5 cm, the width of the leaflets is 1-2.5 cm, the tips of the leaflets are sharp to round and blunt, the leaflets are thin and tapered, the base parts of the leaflets are wedge-shaped, the edges of the leaflets are provided with sharp to round and blunt sawteeth, the upper parts of the leaflets are green, the leaflets are dredged and velveteen, the lower parts of the leaflets. The raceme is single or 2-3 in the stem top; bracts are usually 3 deep-split, strip-shaped, small bracts facing each other, oval; sepals 5, triangular ovoid; petal 5, long round, yellow; 5-15 parts of stamens; style 2, threadlike, head-like. The thin fruit is inverted oval-shaped, 10 ribs are arranged outside the thin fruit, the thin fruit is dredged and velvety, a plurality of layers of barbs are arranged at the front end of the thin fruit, the thin fruit is upright when young, and the thin fruit is close to the inside when mature. The flowering and fruit period is 5-12 months. Living under creeks, roadside, grasslands, shrubs, forest borders and sparse forests. The distribution is in every region of China. The conical shape is characterized in that the middle upper part is bent normally, the total length is 2-6 cm, the diameter is 0.5-1 cm, and the top is wrapped with a plurality of light brown membranous bud scales. The rootstock is shortened, cylindrical and 1-3 cm long. The surface is dark brown, and has compact annular nodes with dark degraded scale leaves, and few adventitious roots sometimes remain at the lower part of the rhizome. The root sprouts are brittle and fragile, and the broken section is flat and yellow-white. Slight smell, slightly bean-like smell, slightly sweet and bitter taste. It has effects in expelling parasites, removing toxic materials, and relieving swelling. Belongs to the category of blood-activating and stasis-resolving herbs. It mainly contains agrimophol, agrimonol, apigenin, catechol, tannin, etc. The agrimophol mainly acts on the cestode head segment, has the effects on the neck segment and the somite body segment, can inhibit glycogenolysis of the worm body, and has obvious inhibition effects on anaerobic and aerobic metabolism of cells of the worm body and generation of a metabolite succinic acid of the cells of the worm body; the agrimophol has the functions of promoting the transfer of schistosome, the atrophy and degeneration of the body of an animal and even killing imagoes; has long-lasting excitation effect on roundworm and also has inhibition and killing effect on trichomonas vaginalis, schistosome, plasmodium, cysticercus and the like.
The chemical components of the traditional Chinese medicine plant are very complex, and the traditional Chinese medicine plant not only contains various effective components, but also contains ineffective components and toxic components. Extracting the effective components of the effective monomers, and further separating and purifying the effective components to obtain the effective monomers is an important content in the research field of traditional Chinese medicines. The extraction of the traditional Chinese medicine is to extract the effective components in the traditional Chinese medicine to the maximum extent by utilizing certain technologies, so that the internal quality and the clinical treatment effect of the traditional Chinese medicine preparation are improved, and the effect of the traditional Chinese medicine is exerted to the maximum extent.
Disclosure of Invention
The invention discloses a preparation method and application of a hairyvein agrimonia herb bud extract. The preparation process is summarized through long-term scientific research, and is characterized by simple and economic process, environmental protection and large-scale production.
One of the purposes of the invention is to provide an agrimony bud extract.
Another object of the present invention is to provide a method for preparing said extract of Agrimonia pilosa bud.
It is another object of the present invention to provide an insect repellent compound.
It is still another object of the present invention to provide a composition comprising the above compound or extract.
It is also an object of the present invention to provide the use of the above compound or the composition.
It is another object of the present invention to provide a method for controlling insect-repellent using the above compound or composition.
In order to realize the purpose, the invention adopts the following technical scheme:
the agrimony bud extract is characterized by being prepared by the following method: crushing fresh or dried agrimony buds, mixing with water or ethanol with the mass of 5-15 times, performing reflux extraction for 1-3 times for 0.5-3 hours each time, combining filtrates, concentrating under reduced pressure, steaming to obtain thick paste with the relative density of 1.2-1.35 at 55 ℃, and drying under reduced pressure to obtain the agrimony bud.
Preferably, the relative density when concentrated to 55 ℃ is 1.25 to 1.30.
Preferably, the gemma agrimoninae is selected from leaves and roots.
More preferably, the agrimony bud extract is prepared by the following method:
(1) mixing a certain amount of agrimony buds with water or ethanol according to the mass ratio of 1: 5-1: 15, performing reflux extraction for 1-3 times, each time for 0.5-3 hours, and combining filtrates;
(2) concentrating the filtrate obtained in the step (1) to a relative density of 1.2-1.35 at 55 ℃, and drying under reduced pressure to obtain the extract.
Preferably, the reduced pressure drying condition is 0.02 Mpa-0.15 Mpa, and the drying is carried out for 24-48 h at the temperature of 40-60 ℃.
The invention also provides an insect-repellent compound, which is prepared by the following method: recrystallizing the extract to obtain the compound shown as the following formula:
Figure BDA0002371968530000031
preferably, the solvent for recrystallization is water and ethanol in a volume ratio of 1: 1.
The invention also provides a composition containing the extract or the compound and an auxiliary agent.
The compound can be used for preparing anthelmintic drugs.
The endoparasite control agent of the present invention exhibits an excellent antibody endoparasite effect and exerts a definite control effect on endoparasites. The animals to which the endoparasite-controlling agent of the present invention can be applied belong to mammals other than humans or birds. Examples of the non-human mammals include: domestic animals such as pig, horse, cattle, sheep, goat, rabbit, camel, buffalo, deer, mink, and hairline; pets such as dogs, cats, birds, monkeys, etc.; experimental animals such as rats, mice, golden hamsters, and guinea pigs, and the birds include: chicken, wild duck, hybrid duck, quail, duck, goose, turkey, etc.
Endoparasites which are effective as the endoparasite control agent of the present invention and which are parasitic on animals belonging to mammals other than humans or birds are roughly classified into protozoa and helminths. Examples of the protozoon include: eimeria species such as Adenophora, Isospora, Toxoplasma, neospora, Sarcocystis, Peniospore, Hammond, Cryptosporidium, Coccidium species, Haemophilus, Plasmodium species such as Plasmodium, Theileria, Bordetella, Hematodiae, Hemobacter (Heamotenella), Theleplasma species (Piroplasma) such as Allilus, Haemophilus as other Adenophora species, Haemophilus (Haemogergarina) etc., Trypanosoma (Encephalitozon) such as Microsporidium species (Microsporidium), Pediobolus (Nosememaria) etc., Trypanosoma (Trypanosoma) such as Endothioria), Trichophora (Trypanosoma) such as Leishmania (Leishia), Trypanosoma (Trypanosoma), Trichomonas (Trichomonas), Trichomonas (Giardia) etc., Hematodina) such as Trichomonas, Trichomonas (Giardia) and the like, Trichomonas (Giardia) such as Trichomonas, Trichophyta) and the like, Infusorian (Ballantium), Buxton ciliate (Buxtonella), Entodinium, and the like, which are ciliates (Ciliophora),
examples of the worms include: pig roundworm (Ascaris), dog roundworm and cat roundworm (Toxocara), dog Toxocara roundworm (Toxascaris), horse roundworm (Paraascaris), chicken roundworm (Ascaridia), chicken cecum (Heterakis), heteroleptic nematode (Anisakis), roundworm (Ascarida), pinworm (Oxyuris), pinworm (Passalurus), etc. (Oxyurida), strongylidae (Strongylous), Haemonchus contortus (Haemonchus), bovine gastrocnemidae (Ostertagia), Trichostrongylus tricholobus (Trichostrongylus), gulona (Cooperia), Microjugular nematode (Nematobius), red nematode (Hystrongylon), bovine tubercle (Oesophagostomum), Diesophagostomum, Trichostylum caninum), Ancylostomum, Trichostylum canis (Heterodera), Trichostylodes canis (Ostylenchus), Trichostylodes canis, Trichostylodes immaturus), Trichostylodes immaturus (Ostylodes caninum), Trichostyloides), Trichostylodes canis (Osteres (Ostylodes), Trichostylodes canis), Trichostylodes (Ostylodes canis), Ostylodes nervus (Ostylodes canis), Ostylodes (Osbeckia), Ostylodes (Ostylodes), Ostylodes (Ostylodes odorum), Ostylodes (Ostylodes), Ostylodes, Rod nematodes such as Strongyloides (Strongyloides), microteles (Micronema) (Rhabbida), sucking nematodes (Thelazia), neratia acuminata (Oxyspira), cerbroides (Spirocerca), angiostrodia elata (Gongylonema), Derashi nematodes (Draschia), Habrononis (Habronema), Arthropoda nematodes (Ascarops), Physalaria nematoda (Physalopa), Thalata nematodes (Gnathostoma) and other Strongyloides (Spirurida), Dirofilaria immitis (Dirofilaria), Dirofilaria equina (Setaria), Dipicria echinochinea (Dipylonema), Paraserina (Parafilria), Spirostria coccinella (Chorista), Trichosporoides (Trichosta), Trichosporoides (Trichosporoides), Trichosporoides (Trichosta), etc., Trichosporoides (Trichosporoides), Trichosporoides (Trichosta), Trichosta (Trichosporoides), etc.) Examples of the insect pests include dipteroides (Heterophaga), epididymides (Trichotrema), dipteroides (Dicrooelium) and the like (Dicrocoelata), urodes (Pharyngostoma), dipteroides (Alaria) and the like (Dipinostata), Echinostomides (Echinostoma), Echinochloa (Echinochastoma) and the like (Echinochastoma), paragonia (Paragonimus), Bradyma (Paragonimus), Bradygulis (Nanophytus) and the like (Zotrema), epididymides (Schizobium), paragonidia (Heterophaga) and the like (Schizobium), hypotrichomonas, paragonidia (Heterophaga) and the like (Heteroschistosoma), hypotrichomonoides and the like (Heterophagostomula), hypotrichoides, schistosomides (Hyphomyces), hypotrichoides, and the like (Zostera), hypotenus (Zona), hypotenus, and the like (Zona), hypotenus, taenia, hypotenus, and the like (Zona), and the like (Zona, the like (Zona), the like (Zona), the like (, Bean-shaped tapeworm, cestolochia (Tenia), cat tapeworm (Hydotigera), multiheaded tapeworm (Multiceps), single-package tapeworm (Echinococcus), multi-package tapeworm (Echinococcus), hooked tapeworm (Taenia), unhooked tapeworm (Taeniahrynchus), circumcissus (Hymenolepis), small-form tapeworm (Vampilis), square tapeworm (Raillitina), circular-leaf tapeworm (Cyclopellidia) such as wedge tapeworm (Amoebeoebae), etc., Canadian caninum (Macranthonchus) as a filarial species, Moniliforme candida (Moniliformis), etc., Caninium caninum (Linguatia) as a lingualis, etc., and various parasites, but not limited thereto.
Further, as the helminths, parasites belonging to the following species and various parasites belonging to the echinoderm and the lingual helminth are mentioned by other names, but not limited thereto, for example:
examples of the genus nematoda (Enoglida) include: the genus rhabdus (rhabditis) includes, for example, a species of whipworm (trichissp.), a species of telangiectasia (capillarispp.), a species of trichogramma (trichomonas), a species of strongyloides (strongyloides), and the like, and the genus strongyloides (strongyloides) includes, for example: circular nematode species (stronyusspp.), trilobious nematode species (trichontophorus pp.), similias hexadentalis species (gyalon phalyphylla sp.), colubrium nematoda species (cylophorophus fasciatus sp.), trichinella (scleroderma phalospp.), columella nematoda species (cyrophus xylophilus sp.), tuberosum nematoda species (Oesophagostomus sp.), columbium nematoda species (Bubertoth phalus sp.), Cyclocercux cuneatus sp.), calix nematoda (cyrosodella phalus trichinella (scleroderma), Buphalothyriasis japonica trichum nematoda (Buphalia trichum), Buckoo nematoda phylum nematoda species (Buckoo phylum nematoda), Buckoo nematoda phylum trichum, Buckoo nematoda phylum nematoda species (Buckoo phylum nematoda phylum sp.), Buckoo phylum nematoda species (Buckoo phylum nematoda), Buckoo phylum nematoda species (Bucko, Buckoo phylum nematoda phylum, Buckoo phylum nematoda, Buckoo species (Buckoo), Buckoo phylum nematoda, Strongopus (Strongopus), Strongrass (Strongopus, Strongrass species (Strongopus), Strongopus sp.), Buckoo species (Strongrass), Strongopus (Strongopus), Strongrass sp.), Strongopus species (Strongrass), Strongrass species (Strongrass), Strongopus sp.), Strongrass (Strongrass sp.), Strongrass (Strongras, Cyclo (Strongylostoma sp.), Pararenosoma sp, Haemonchus species (Angiostrongylusspp.), Strongylostoma catus (Aeurostrongylusspp.), Strongyloides similis (Filaroid spp.), Strongyloides paraphaeformis (Parafilarius spp.), Strongyloides trichogrammae (Trichostrongylus spp.), Strongyloides (Haemonchusspp.), Ostertaginella (Ostertagaspp.), Strongyloides (Marshallogiaspp.), Strongyloides rugosus sp.), Strongyloides ruguloides (Cooperiasepp.), Strongyloides tenuis (Nematodurus spp.), Strongyloides (Ostertagosspp.), Strongyloides (Marshalolongylusspp.), Strongyloides (Ostertagou. sp.), Strongyloides sp., Strongyloides (Ostertagou. sp.), Strongyloides (Ostertagou) (Ostertagou. sp.), Strongyloides spp.),
examples of the enterobiasis (Oxyurida) include: the ascaridae (Ascaridia) include, for example: ascaris species (Ascarisspp.), toxocarpa species (toxocarspp.), toxocarpa species (toxocarpp.), toxocarpa crus, ascaris suum species (parascarispp.), anistreponema species (anisakispp.), anisakis species (anisakispp.), and chicken ascaris species (ascaris spp.), and the like, and examples of the genus helicobacter (Spiruride) include: species of Trichophyton sp (Gnathosmaspp.), Ostertagia species (Physalopetera pp.), Heterodera glecta species (Thelaziaspp.), Cylindrocarpon species (Gongylonemasp.), Nematoda species (Habronemasp), Paralexophaga seri species (Parabremamspp.), Desiraptera species (Draschipaspp.) and Longipexophaga species (Dracukusspp.), etc., and as the genus of filaria (Filarida), there are exemplified: crown filarial species (Stephanoferiaspp.), accessory filarial species (Parafiaspip.), bristlegrass filarial species (Setarispp.), Arctia filamentosa (Loaspp.), Dirofilariaspip, Photofilarial species (Litomosoidesp.), Brugiaspip (Brugiaspip.), Wuchereriasp, Wuchnereis species (Onchocercaspp.), etc.,
examples of the filarial (Acanthocephala) include: examples of the subclasses of the monogenus (Monogenea) of the flukes include the species filarial cervidae (filaiolisspp.), the species monilialrmisspp (Moniliformisspp), the species megakiss (macacanthus), and the species epididymitis (prosthenorchispp), and the like, and as the subclasses of the monogenus (Monogenea) of the flukes, there are: the third generation worm species (gyromactylusssp.), the dactylogyrusssp, and the pleomophaga species (Polystomaspp.) and the like, and as the subclasses of the second generation, for example: the two-hole fluke (dipostompp.), the stem-hole fluke (posthoprostommspp.), the blood fluke (schistosomasp.), the hair-blood fluke (tricholobutrasp.), the ornithiziaspora (leichholziaspp.), the Australian fluke (austria fluke), the giant fluke (giga), the cercaria fluke (giga fluke), the cercaria fluke (leichp.), the brachypodium fluke (xylophaga), the brachypodium fluke (echinoderma fluke), the echinodera fluke (hypotenus, the hypotenus fluke (hypotenus, hypotenus (hypotenus), the hypotenus (hypotenus fluke, hypotenus (hypotenus, hypot, Broad disc sucker species (Eurytemaspp.), cryptate sucker species (Troglotremaspp.), paralogous sucker species (Paragoniumusspp.), bean-shaped anal tumor sucker species (Collyclizumspp.), dwarf sucker species (Nanophytusspp.), epididymis sucker species, clonorchis sinensis species, sublithromyces lactis species, dysmorphism sucker species, metazoa sucker species and the like,
examples of the pseudofola of tapeworms include: the schizocephala species (diphylobothriumspp.), the tapeworm species, the schizocephala species, the lingualistic tapeworm species (Ligulaspp.), the trefoil tapeworm species (bothriumspp.) and the large-multiple-reproduction-hole tapeworm species (diplonoplophora spp.) are listed as the order of the orbicularia (cyclophyllea), for example: mesogenital-cestodes (Mesothecoidesspp.), anocephalic cestodes (Anoplocephala pp.), Paratopocehasolas (Avitelliaspp.), Meniere cestodes (Moniezippp.), Thysanosoma spp., Quzi uterine cestodes (Thysanieiziaspp.), vitellogona-free cestodes (Avitelinaspp.), Western-style cestodes (Stilesiaspp.), cestotidae (Cittaemiaspp.), Andy. cestodes (Andrew.) et.), Bioparasitic cestodes (Berteriopsis spp.), Echinococcus spp. (Echinococcus spp.), Ditaenigma-taenigma (Hyrteriopsis spp.), Echinococcus spp., Echinococcus spp (Hypodermata, Echinococcus spp.), Echinococcus spp., Echinococcus spp (Echinococcus spp.), Echinococcus spp., Echinococcus strains (Echinococcus spp.), and Echinococcus strains (Echinococcus spp.).
The endoparasite-controlling agent of the present invention exhibits an effect not only on parasites residing in intermediate and final hosts but also on parasites in the parasite-protecting host organism. In addition, the compounds of the general formula (I) according to the invention show an effect throughout the development stage of the parasite. For example, in protozoa, the protozoan include cysts, prepackages, vegetative or asexual mitogens, amoebae, gametocytes, gametes, fusions and cytosomes in sexual reproduction. Among the nematodes are eggs, larvae, and adults. Furthermore, the compounds of the invention are not only capable of repelling parasites within organisms, but also capable of preventively preventing infection by parasites by administration in the context of the route of infection. For example, it can prevent soil-borne infections from upland and park soils; percutaneous infection from river, lake, marsh, paddy field, etc.; oral infection of feces from animals such as dogs and cats; oral infection of raw meat from marine fish, freshwater fish, crustacean, shellfish, livestock, etc.; infections from mosquitoes, gadflies, flies, cockroaches, mites, fleas, lice, bug bugs, chiggers, etc. are equal to those in the past.
The endoparasite control agent of the present invention can be administered for the purpose of treating or preventing parasitic diseases as a drug for animals belonging to mammals other than humans or birds. The administration method may be either oral administration or non-oral administration. In the case of oral administration, it can be administered by mixing with, for example, a capsule, a tablet, a pill, a powder, a granule, a fine granule, a powder, a syrup, an enteric agent, a suspension, a paste, or a liquid beverage or feed for animals. In the case of non-oral administration, it is administered as a dosage form such as injection, drip, suppository, emulsion, suspension, drop, ointment, cream, liquid, lotion, spray, aerosol, cataplasm, tape, to maintain mucosal or transdermal absorption.
When the endoparasite-controlling agent of the present invention is used as a drug for animals belonging to mammals other than humans or birds, the optimum amount (effective amount) of the active ingredient varies depending on the treatment or prevention, the kind of the infected parasite, the type and degree of infection, the formulation and the like, and generally, in the case of oral administration, it is in the range of about 0.0001mg/kg body weight to 10000mg/kg body weight per day. In the case of non-oral administration, in the range of about 0.0001mg/kg body weight to 10000mg/kg body weight per day, single administration or divided administration.
In general, the concentration of the active ingredient in the endoparasitic control agent of the present invention is from about 0.001 to about 100% by mass, preferably from about 0.001 to about 99% by mass, and more preferably from about 0.005 to about 20% by mass. The endoparasite control agent of the present invention may be a composition to be administered directly or may be a high-concentration composition to be used after being diluted to an appropriate concentration at the time of use.
In addition, in order to enhance or supplement the effect of the endoparasite-controlling agent of the present invention, conventional endoparasite-controlling agents may be used in combination. In the case of combined use, two or more active ingredients may be mixed before administration to give a preparation, or two or more different preparations may be administered separately.
Examples
The invention is further illustrated by the following examples. It should be understood that the method described in the examples is only for illustrating the present invention and not for limiting the present invention, and that simple modifications of the preparation method of the present invention based on the concept of the present invention are within the scope of the claimed invention. All the starting materials and solvents used in the examples are, unless otherwise specified, commercially available analytical pure products.
Preparation example 1:
(1) pulverizing fresh herba Agrimoniae 5Kg, mixing with water at a mass ratio of 1:15, reflux-extracting for 3 times each for 3 hr, and mixing filtrates;
(2) concentrating the filtrate in step (1) to relative density of 1.25 at 55 deg.C, and drying under reduced pressure to obtain 0.5Kg (G-1) of extract.
The reduced pressure drying condition is about 0.15Mpa, and the drying is carried out for 24 hours at the temperature of 50 ℃.
Preparation example 2:
(1) pulverizing fresh herba Agrimoniae 5Kg, mixing with ethanol at a mass ratio of 1:10, reflux-extracting for 3 times (each for 3 hr), and mixing filtrates;
(2) concentrating the filtrate in step (1) to relative density of 1.35 at 55 deg.C, and drying under reduced pressure to obtain 0.6Kg (G-2) of extract.
The reduced pressure drying condition is about 0.15Mpa, and the drying is carried out for 24 hours at the temperature of 50 ℃.
Preparation example 3:
taking 5G of the agrimony bud extract with the number of G-1 in the preparation example 2, heating and dissolving the agrimony bud extract by 50mL of absolute ethyl alcohol, and slowly dripping 25-30mL of water; after obtaining pale yellow crystalline solid, it was again dissolved with 50mL of anhydrous ethanol, and 25-30mL of water was slowly added dropwise to give pale yellow needle-like solid compound.
Figure BDA0002371968530000111
1H NMR(400MHz,DMSO-d6)δ9.06(s,1H,phenol),7.22(d,2H,benzene),6.68(dd,2H,benzene),6.19(d,1H,CH),5.82(m,1H,CH),5.50(t,1H,CH),5.13(d,1H,CH),4.88(d,1H,CH),4.49(dd,1H,CH),3.27(s,3H,CH3),2.71(m,1H,CH),2.58(m,1H,CH),2.36(s,2H,CH2),2.29(s,2H,CH2),1.86(dd,2H,CH2),1.54(dd,2H,CH2),0.91(d,3H,CH3).
Biological activity example 1: in vivo Activity assay for Haemonchus
In 96-well plates, 20L 1-stage larvae per well (twirling cord of HaemophilusWorms) so that they can move freely, a solution of the extract of the invention and the compound dissolved in DMSO at a predetermined concentration (final concentration of DMSO is 0.78% (v/v)) was added to each well at 0.5 μ Ι/well. The plates were maintained at 27 ℃/95% RH for 4 days. Examining the locomotor ability of the larvae and determining the concentration (EC) required to inhibit 50% of the locomotor ability50). Based on EC50The values, activities against haemonchus were graded according to the criteria shown below and the results are shown in the table below.
Grading standard:
a: e C50 is less than 0.5 ppm.
B: EC50 values were above 0.5ppm but below 5 ppm.
C: the EC50 value is 5ppm or more.
Test specimen Grade EC50(ppm)
Preparation of example 1 B 0.61
Preparation of example 2 B 0.60
Preparation of example 3 A 0.02
Biological activity example 2: in vitro assay for determining activity of ascaris suum mitochondrial complex II
Ubiquinone-2 (UQ) as an electron acceptor was added to 50mM potassium phosphate pH 7.4-0.1% (w/v) sucrose monolaurate solution2) The resulting mixture was allowed to stand at 25 ℃ for 20 minutes at a final concentration of 60. mu.M. Potassium cyanide (final concentration 2mM) was added thereto, mitochondria prepared from the muscle of adult ascaris suum were added, well mixed, various concentrations of the extract of the present application and the compound were added thereto, and left to stand at 25 ℃ for 3 minutes. The enzyme reaction was started by adding potassium succinate (final concentration 10mM) and the UQ was measured at 278nm2Change in absorbance (e.g. 1.5X 10)4M-1cm-1) From this, the enzyme activity is calculated, and the IC is determined from the concentration of the test agent and the degree of inhibition50See table below.
Test specimen IC50(nm)
Preparation of example 1 6.61
Preparation of example 2 6.32
Preparation of example 3 1.22

Claims (9)

1. The agrimony bud extract is characterized by being prepared by the following method: crushing fresh or dried agrimony buds, mixing with water or ethanol with the mass of 5-15 times, performing reflux extraction for 1-3 times for 0.5-3 hours each time, combining filtrates, concentrating under reduced pressure, steaming to obtain thick paste with the relative density of 1.2-1.35 at 55 ℃, and drying under reduced pressure to obtain the agrimony bud.
2. The Agrimonia pilosa bud extract of claim 1, wherein: the relative density of the concentrate at 55 ℃ is 1.25-1.30.
3. The Agrimonia pilosa bud extract of claim 1, wherein: the bud of Agrimonia pilosa is selected from the group consisting of leaf and root.
4. The Agrimonia bud extract according to claim 1, prepared by the following method:
(1) mixing a certain amount of agrimony buds with water or ethanol according to the mass ratio of 1: 5-1: 15, performing reflux extraction for 1-3 times, each time for 0.5-3 hours, and combining filtrates;
(2) concentrating the filtrate obtained in the step (1) to a relative density of 1.2-1.35 at 55 ℃, and drying under reduced pressure to obtain the extract.
5. The Agrimonia bud extract as recited in claim 4, wherein: the reduced pressure drying condition is 0.02 Mpa-0.15 Mpa, and the drying is carried out for 24-48 h at the temperature of 40-60 ℃.
6. An insect repellent compound characterized by being prepared by the following method: recrystallizing the extract of any one of claims 1 to 5 to obtain the compound of formula:
Figure FDA0002371968520000011
7. an insect repellent compound according to claim 7, wherein: the solvent for recrystallization is water and ethanol, and the volume ratio of the water to the ethanol is 1: 1.
8. A composition comprising an extract according to any one of claims 1 to 5, or a compound according to any one of claims 6 to 7, and an adjuvant.
9. Use of a compound according to any one of claims 6 to 7 for the manufacture of an anthelmintic.
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Publication number Priority date Publication date Assignee Title
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106963760A (en) * 2012-08-30 2017-07-21 国立大学法人东京大学 Purposes of the endoparasite control agent in the medicine for preparing preventing and treating endoparasite

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