CN107929243A - A kind of thiabendazolum dry suspensoid agent and preparation method thereof - Google Patents
A kind of thiabendazolum dry suspensoid agent and preparation method thereof Download PDFInfo
- Publication number
- CN107929243A CN107929243A CN201711305918.7A CN201711305918A CN107929243A CN 107929243 A CN107929243 A CN 107929243A CN 201711305918 A CN201711305918 A CN 201711305918A CN 107929243 A CN107929243 A CN 107929243A
- Authority
- CN
- China
- Prior art keywords
- thiabendazolum
- weight
- parts
- dry suspensoid
- agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- WJCNZQLZVWNLKY-UHFFFAOYSA-N thiabendazole Chemical compound S1C=NC(C=2NC3=CC=CC=C3N=2)=C1 WJCNZQLZVWNLKY-UHFFFAOYSA-N 0.000 title claims abstract description 60
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 58
- 238000002156 mixing Methods 0.000 claims abstract description 22
- 238000012856 packing Methods 0.000 claims abstract description 11
- 238000000227 grinding Methods 0.000 claims abstract description 10
- 238000009736 wetting Methods 0.000 claims abstract description 5
- 239000000375 suspending agent Substances 0.000 claims abstract description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 6
- 229930006000 Sucrose Natural products 0.000 claims description 6
- 239000005720 sucrose Substances 0.000 claims description 6
- 229920002472 Starch Polymers 0.000 claims description 5
- 239000008107 starch Substances 0.000 claims description 5
- 235000019698 starch Nutrition 0.000 claims description 5
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 4
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 claims description 4
- 229920002125 Sokalan® Polymers 0.000 claims description 4
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 4
- 229960001631 carbomer Drugs 0.000 claims description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
- 239000008103 glucose Substances 0.000 claims description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 4
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 4
- 235000019359 magnesium stearate Nutrition 0.000 claims description 4
- 229920000609 methyl cellulose Polymers 0.000 claims description 4
- 239000001923 methylcellulose Substances 0.000 claims description 4
- 235000010981 methylcellulose Nutrition 0.000 claims description 4
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 4
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 4
- -1 sorbierite Chemical compound 0.000 claims description 4
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- 235000010413 sodium alginate Nutrition 0.000 claims description 3
- 239000000661 sodium alginate Substances 0.000 claims description 3
- 229940005550 sodium alginate Drugs 0.000 claims description 3
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- 239000004925 Acrylic resin Substances 0.000 claims description 2
- 108010011485 Aspartame Proteins 0.000 claims description 2
- 241000416162 Astragalus gummifer Species 0.000 claims description 2
- 229920002101 Chitin Polymers 0.000 claims description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims description 2
- 229920001615 Tragacanth Polymers 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- 235000010489 acacia gum Nutrition 0.000 claims description 2
- 239000001785 acacia senegal l. willd gum Substances 0.000 claims description 2
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- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 2
- 229960003438 aspartame Drugs 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 2
- 229920002301 cellulose acetate Polymers 0.000 claims description 2
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 claims description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 2
- 229960001545 hydrotalcite Drugs 0.000 claims description 2
- 229910001701 hydrotalcite Inorganic materials 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 229960003511 macrogol Drugs 0.000 claims description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 2
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 2
- 239000000347 magnesium hydroxide Substances 0.000 claims description 2
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 229940085605 saccharin sodium Drugs 0.000 claims description 2
- 235000010487 tragacanth Nutrition 0.000 claims description 2
- 239000000196 tragacanth Substances 0.000 claims description 2
- 229940116362 tragacanth Drugs 0.000 claims description 2
- 229920001285 xanthan gum Polymers 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 150000001336 alkenes Chemical class 0.000 claims 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 239000003292 glue Substances 0.000 claims 1
- 239000008101 lactose Substances 0.000 claims 1
- 239000003595 mist Substances 0.000 claims 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims 1
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- 239000010703 silicon Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 34
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- 238000004062 sedimentation Methods 0.000 description 9
- 239000000725 suspension Substances 0.000 description 8
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
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- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 102000002322 Egg Proteins Human genes 0.000 description 3
- 108010000912 Egg Proteins Proteins 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
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- 210000004681 ovum Anatomy 0.000 description 3
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- 229960004546 thiabendazole Drugs 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000005374 Poisoning Diseases 0.000 description 2
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- SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 2
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- 238000005550 wet granulation Methods 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical group CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- 229930195730 Aflatoxin Natural products 0.000 description 1
- XWIYFDMXXLINPU-UHFFFAOYSA-N Aflatoxin G Chemical compound O=C1OCCC2=C1C(=O)OC1=C2C(OC)=CC2=C1C1C=COC1O2 XWIYFDMXXLINPU-UHFFFAOYSA-N 0.000 description 1
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
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- YRWLZFXJFBZBEY-UHFFFAOYSA-N N-(6-butyl-1H-benzimidazol-2-yl)carbamic acid methyl ester Chemical compound CCCCC1=CC=C2N=C(NC(=O)OC)NC2=C1 YRWLZFXJFBZBEY-UHFFFAOYSA-N 0.000 description 1
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- 230000004888 barrier function Effects 0.000 description 1
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- FFLJZFAEPPHUCU-UHFFFAOYSA-N benzene;thiophene Chemical compound C=1C=CSC=1.C1=CC=CC=C1 FFLJZFAEPPHUCU-UHFFFAOYSA-N 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- 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
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Abstract
A kind of thiabendazolum dry suspensoid agent and preparation method thereof, is prepared from the following parts by weight of the components：0.1~20 parts by weight of thiabendazolum, 0.1~10 parts by weight of suspending agent, 0.1~20 parts by weight of wetting glidant, 50~99.7 parts by weight of flavouring.Using superfine communication technique, main ingredient thiabendazolum and auxiliary material are subjected to ultramicro grinding respectively, then mixing packing is carried out, the drawbacks of so both having avoided the powder flowbility difference that occurs in common preparation method and easily layering, while the problems such as the pelletization that turn avoid the appearance of granular pattern dry suspensoid agent is easily lumpd, the particle drying time is longer, particle easy friability.The present invention is uniformly dispersed, and because mixing is uneven when overcoming pre-mixing agent or the use of pulvis spice, or feeding decline causes drug effect undesirable after livestock and poultry morbidity, it also avoid taking the phenomenon that the high feed of local drug concentration causes to be poisoned；Dry suspensoid agent is big compared with the specific surface area of pre-mixing agent at the same time absorbs rapid, bioavilability height, cure rate higher.
Description
Technical field
The invention belongs to pharmaceutic preparation for livestock technical field, and in particular to a kind of thiabendazolum dry suspensoid agent for animals, also
It is related to the preparation method of the medicament.
Background technology
Thiabendazolum,（Thiabendazole, Tiabendazole, Mintezol）, it is benzimidazole anthelmintic, extensively
Anthelmintic is composed, has expeling effect to a variety of gastrointestinal nematode parasites of animal, it is good to adult effect, also there is one to be set for prematurity polypide
With.Thiabendazolum is a kind of inhibitor of polypide fumaric reductase.The catalytic reaction of fumaric reductase is glycolysis
During an essential part, many parasitic worms are all to obtain energy source by this process, if this mistake
Journey is obstructed, then obstacle occurs for polypide metabolism.Since parasite utilizes glycolytic cycle and the anaerobic metabolism host's aerobic with it
Fundamental metabolic pathway is different.Therefore thiabendazolum is harmless to host.Confirm that thiabendazolum is to pass through parasite according to another in vitro test
The lipoids barrier of cuticula and absorbed.At present it is believed that benzimidazole anthelmintic is all cellular tubulin suppression
Agent, while be also energetic supersession inhibitor, i.e. medicine can absorb nourishment necessary structural proteins-micro- with parasite cell one kind
Tubulin combines, particularly dimer tubulin binding, so as to hamper the polymerization of the tubulin in micro-pipe assembling process.
In addition, the high selectivity of polypide is acted on, and plays anti parasitic effect efficiently, less toxic.Thiabendazolum gives birth to dermatitis bud
Bacterium, Candida albicans, Penicillium notatum and trichophyte etc. have inhibitory action, can also reduce the formation of aflatoxin in feed.Thiophene
Parbendazole can be absorbed rapidly by animal alimentary canal, and be distributed widely in body most tissues, thus to migratory stage children in tissue
Worm and the adult parasitized in enteric cavity and intestinal wall kill effect.2-7h blood concentration peakings after pig, sheep, ox administration.
Thiabendazolum is white or off-white powder, and slightly soluble, almost insoluble in chloroform or benzene in water, in dilute hydrochloric acid
Dissolving, mildly bitter flavor are odorless.At present, that circulates on domestic and international market has thiabendazolum piece, thiophene benzene with the relevant formulation of thiabendazolum
Up to azoles oral suspensions and thiabendazolum emulsion, these medicines are only used for people's medicine；Only have bulk pharmaceutical chemicals on veterinary drug, there is no relevant dose
Type.
Powder or shot-like particle is made for insoluble solid medicine and proper auxiliary materials in dry suspensoid agent, faces the used time and adds water shaking i.e.
Suspension is dispersed into for oral liquid preparation.After dry suspensoid agent adds moisture to dissipate, the quality requirement of supensoid agent should be met, be suspended
Particulate in liquid should be dispersed, should not sink rapidly, and cake block should not be formed after sedimentation, rapid scattered again after shaking.It is dry
Supensoid agent is the novel form to grow up on the basis of supensoid agent, has physically better stability than supensoid agent, existing solid
The characteristics of body preparation, be such as convenient for carrying, convenient transportation, and stability is good etc., and has the advantage of liquid preparation, such as conveniently takes, and inhales
Receive rapid.Compared with pre-mixing agent or pulvis, when its use, adds water to become solution, and is uniformly dispersed, and overcomes pre-mixing agent
Or because mixing is uneven during the use of pulvis spice, or feeding decline causes drug effect undesirable after livestock and poultry morbidity, it also avoid taking
The high feed of local drug concentration causes the phenomenon of poisoning；Dry suspensoid agent is big compared with the specific surface area of pre-mixing agent at the same time absorbs rapidly,
Bioavilability is high, cure rate higher.
The preparation method of prior art dry suspensoid agent mainly has two kinds：One kind is to divide medicine after mixing with auxiliary material
Dress, this method are prepared simply, but powder flowbility difference and easily layering；Another kind is wet granulation process, what the current country disclosed
The preparation method of dry suspensoid agent is mostly wet granulation process, and this method granulation presence is easily lumpd, the particle drying time is longer, particle
The problems such as easy friability and more powder.
The content of the invention
The technical problem to be solved in the present invention is poor and easy point of the powder flowbility that dry suspensoid agent occurs in common preparation method
The technical problem of layer, to solve the above problems, providing a kind of thiabendazolum dry suspensoid agent and preparation method thereof.
The purpose of the present invention is what is realized in the following manner：
A kind of thiabendazolum dry suspensoid agent, is prepared from the following parts by weight of the components：0.1~20 parts by weight of thiabendazolum, help
0.1~10 parts by weight of suspension, 0.1~20 parts by weight of wetting glidant, 50~99.7 parts by weight of flavouring.
Above-mentioned thiabendazolum dry suspensoid agent, the suspending agent is methylcellulose, sodium carboxymethylcellulose, hydroxypropyl first
Base cellulose, cellulose acetate, hydroxypropyl cellulose, hydroxyethyl cellulose, polyvinylpyrrolidone, Arabic gum, xanthans,
Tragacanth, carbomer, sodium alginate, hydroxypropyl methylcellulose phthalate, hydroxypropyl methyl cellulose acetate,
One kind in polyacrylic resin, polyvinyl alcohol, polyethylene glycol or chitin or at least two.
Above-mentioned thiabendazolum dry suspensoid agent, the wetting glidant is superfine silica gel powder, lauryl sodium sulfate, dodecane
Base sodium sulfonate, Macrogol 6000, talcum powder, calcium carbonate, magnesium chloride, magnesium hydroxide, Hydrotalcite, magnesium stearate, hydroxide
Aluminium, starch, one kind in pre-paying starch or at least two.
Above-mentioned thiabendazolum dry suspensoid agent, the flavouring is sucrose, glucose, xylitol, sorbierite, mannitol, breast
One kind in sugar, glycyrrhetate, Steviosin, saccharin sodium, aspartame or at least two.
The preparation method of above-mentioned thiabendazolum dry suspensoid agent, it is characterised in that：After each component is separately dried, Ultramicro-powder
It is broken, 200 mesh sieves are crossed, are weighed after mixing according to prescription, packing, you can.
The present invention uses superfine communication technique, and main ingredient thiabendazolum and auxiliary material are carried out ultramicro grinding respectively, then carried out
Mixing packing, the drawbacks of so both having avoided the powder flowbility difference occurred in common preparation method and be easily layered, turn avoid at the same time
The problems such as pelletization that granular pattern dry suspensoid agent occurs easily is lumpd, the particle drying time is longer, particle easy friability.The present invention point
Dissipate uniformly, decline of searching for food because mixing is uneven when overcoming pre-mixing agent or the use of pulvis spice, or after livestock and poultry morbidity causes drug effect
It is undesirable, it also avoid taking the phenomenon that the high feed of local drug concentration causes to be poisoned；Dry suspensoid agent is compared with pre-mixing agent at the same time
Specific surface area is big to absorb rapid, bioavilability height, cure rate higher.
Embodiment
For ease of those skilled in the art's the understanding of the present invention, there is provided following embodiments do furtherly the present invention
It is bright, but embodiment is not as limitation of the present invention.
Example 1：A kind of preparation method of thiabendazolum dry suspensoid agent, weighs 5 parts by weight of medicine thiabendazolum, then weigh with
Lower auxiliary material：5 parts by weight of methylcellulose, 20 parts by weight of lauryl sodium sulfate, 70 parts by weight of sucrose.Medicine and auxiliary material are distinguished
After drying, ultramicro grinding, crosses 200 mesh sieves, is weighed after mixing according to prescription, packing, you can.
Example 2：A kind of preparation method of thiabendazolum dry suspensoid agent, weighs 5 parts by weight of medicine thiabendazolum, then weigh with
Lower auxiliary material：5 parts by weight of sodium carboxymethylcellulose, 15 parts by weight of superfine silica gel powder, 75 parts by weight of glucose.By medicine and auxiliary material point
Not Gan Zao after, ultramicro grinding, cross 200 mesh sieves, according to prescription weigh after mixing, packing, you can.
Example 3：A kind of preparation method of thiabendazolum dry suspensoid agent, weighs 10 parts by weight of medicine thiabendazolum, then weigh
Following auxiliary material：10 parts by weight of carbomer, 20 parts by weight of magnesium stearate, 60 parts by weight of sucrose.Medicine and auxiliary material are separately dried
Afterwards, ultramicro grinding, crosses 200 mesh sieves, is weighed after mixing according to prescription, packing, you can.
Example 4：A kind of preparation method of thiabendazolum dry suspensoid agent, weighs 10 parts by weight of medicine thiabendazolum, then weigh
Following auxiliary material：10 parts by weight of sodium alginate, 20 parts by weight of starch, 60 parts by weight of mannitol.After medicine and auxiliary material are separately dried,
Ultramicro grinding, crosses 200 mesh sieves, is weighed after mixing according to prescription, packing, you can.
Example 5：A kind of preparation method of thiabendazolum dry suspensoid agent, weighs 15 parts by weight of medicine thiabendazolum, then weigh
Following auxiliary material：10 parts by weight of methylcellulose, 20 parts by weight of lauryl sodium sulfate, 55 parts by weight of sucrose.By medicine and auxiliary material
After being separately dried, ultramicro grinding, crosses 200 mesh sieves, is weighed after mixing according to prescription, packing, you can.
Example 6：A kind of preparation method of thiabendazolum dry suspensoid agent, weighs 15 parts by weight of medicine thiabendazolum, then weigh
Following auxiliary material：5 parts by weight of sodium carboxymethylcellulose, 15 parts by weight of superfine silica gel powder, 65 parts by weight of glucose.By medicine and auxiliary material point
Not Gan Zao after, ultramicro grinding, cross 200 mesh sieves, according to prescription weigh after mixing, packing, you can.
Example 7：A kind of preparation method of thiabendazolum dry suspensoid agent, weighs 20 parts by weight of medicine thiabendazolum, then weigh
Following auxiliary material：10 parts by weight of carbomer, 20 parts by weight of magnesium stearate, 50 parts by weight of sucrose.Medicine and auxiliary material are separately dried
Afterwards, ultramicro grinding, crosses 200 mesh sieves, is weighed after mixing according to prescription, packing, you can.
In order to ensure the therapeutic effect of the thiabendazolum dry suspensoid agent of the present invention, quality is carried out to medicine of the present invention and has been ground
Study carefully, the experiment such as safety research, lanqin oral solutions, tests below example can ensure that drug quality of the present invention is reliable, security
It is good, it is curative for effect.
Experiment one：The quality controling research experiment of medicine of the present invention
Dry suspensoid agent belongs to supensoid agent, after adding moisture to dissipate, should meet the quality requirement of supensoid agent, and the medicine in suspension should be uniform
It is scattered, it should not rapidly call in the following text, cake block should not be formed after sedimentation, rapid redisperse is answered after shaking.Preferable supensoid agent, which removes, to be had
There are validity and chemical stability（Depend primarily upon the property of main ingredient）Outside, should also（1）Sedimentation is slow, and energy is gently shaken after sedimentation
Redisperse；（2）The size of suspended particles should remain unchanged in long-term storage；（3）Easily topple over.Therefore, for of the invention real
Thiabendazolum dry suspensoid agent made from example 1~7 is applied, has carried out following quality controling research, including：Character, sedimentation volumn ratio, again
Dispersiveness, medicament contg, heat endurance etc..
（1）Character
Thiabendazolum dry suspensoid agent made from the embodiment of the present invention 1~7 is white or off-white powder, and it is in sticky shape to add after water,
It is layered after standing, supernatant is colourless or micro- Huang, and lower floor is milky white precipitate thing, recovers suspension after vibration.
（2）Medicament contg
Using the content of thiabendazolum in high effective liquid chromatography for measuring thiabendazolum dry suspensoid agent, the results showed that embodiment 1~7
Obtained thiabendazolum dry suspensoid agent content meets the related request in quality standard between the 90%~110% of labelled amount.
（3）Sedimentation volumn ratio
According to《Republic of China Veterinary Pharmacopoeia》Defined method under 2015 editions supensoid agent items, takes thiabendazolum dry-mixed outstanding
Agent 10g purified waters, which mix, to be placed in tool plug graduated cylinder, and record elemental height is H0, is stood after shaking after a certain period of time, observation
The height of lower floor's milky white precipitate thing is H when sedimentation face no longer changes, and sedimentation solvent ratio is calculated by formula F=H/H0.As a result table
Bright, the sedimentation volumn of embodiment 1~7 meets regulation than F.
（4）Weight dispersiveness
After thiabendazolum dry suspensoid agent purified water is disperseed made from embodiment 1~7, after placing 7d in graduated cylinder respectively, survey
Fixed weight dispersiveness, supensoid agent made from embodiment 1~7 after rolling of shaking several times, graduated cylinder bottom sediment can redisperse into uniform
Suspending system, and bottom of bottle thing drug precipitation, shaking, it is fewer to shake number, illustrate that weight is dispersed better.
（5）Study on the stability
After thiabendazolum dry suspensoid agent made from embodiment 1~7 is placed 90d at 40 DEG C, thiabendazolum content is detected, is existed
Between the 90%~110% of labelled amount, and changes of contents is respectively less than 0.03%, shows that the stability of sample is preferable.
Usage and dosage：20 mg/kg weight of dosage, once a day, is used in conjunction 3 days.
Experiment two, Drug safety development test of the present invention
（1）Subjects
Kunming mice 20,18 ~ 22 g of weight.
（2）Test method
Mouse is randomly divided into two groups, every group 10, every group of half male and half female.Fasting（It can't help water）18h.3 prescription of embodiment is added
Water is made 1%（In terms of thiabendazolum）Suspension.Suspension made from test group gavage, dosage are 0.3 mg/g weight, are filled
Stomach is once；Control group gavage equivalent drinking water.By 7 d of mouse conventinal breeding after administration, and observed and recorded day by day.
（3）Result of the test
The results show mouse is of short duration except having after the 1st d perfusions in 7 d after oral liquid made from the gavage embodiment of the present invention 3
Uncomfortable, activity is reduced, and has no that poisoning symptom and death occur for animal.Show thiabendazolum dry suspensoid agent safety prepared by the present invention
Property is good.
Experiment three：The test of pesticide effectiveness of medicine of the present invention
（1）Subjects
It is diagnosed as length × white × big pig 45 of affected pig hoose, 63.4 kg of average weight.Clinical symptoms are become thin for affected pig,
Hair is thick disorderly unglazed, coughs, and expiratory dyspnea, body temperature slightly raises, anorexia.Worm's ovum is detected in excrement.
（2）Test method
Affected pig is randomly divided into 3 groups, every group 15.Suspension made from test group intramuscular injection embodiment 1,10 mg/ of dosage
Kg weight, once a day, is used in conjunction 3 days；Drug control group routinely gives thiabendazolum piece（Thiabendazolum piece is crushed, spice）, give
20 mg/kg weight of dose, once a day, is used in conjunction 3 days；Blank control group is without any processing.Before administration and after administration
The symptom of affected pig is observed, detects the worm's ovum situation in excrement.
（3）Result of the test
The clinical symptoms of the affected pig of the results show test group and drug control group disappear or decline, and appetite rise, temperature recovery is just
Often, hair gloss, weight rise；Worm's ovum in excrement is drastically reduced, or even is disappeared.The affected pig clinical symptoms of blank control group do not have
There is disappearance, the sign for having exacerbation.The experiment illustrates that medicine of the present invention has good anthelminthic effect.
Above-described is only the preferred embodiment of the present invention, it is noted that for those skilled in the art,
Under the premise of general idea of the present invention is not departed from, some changes and improvements can also be made, these should also be considered as the present invention's
Protection domain.
Claims (5)
- A kind of 1. thiabendazolum dry suspensoid agent, it is characterised in that：It is prepared from the following parts by weight of the components：Thiabendazolum 0.1 ~20 parts by weight, 0.1~10 parts by weight of suspending agent, 0.1~20 parts by weight of wetting glidant, 50~99.7 parts by weight of flavouring.
- 2. thiabendazolum dry suspensoid agent according to claim 1, it is characterised in that：The suspending agent is Methyl cellulose Element, sodium carboxymethylcellulose, hydroxypropyl methyl cellulose, cellulose acetate, hydroxypropyl cellulose, hydroxyethyl cellulose, poly- second Alkene pyrrolidone, Arabic gum, xanthans, tragacanth, carbomer, sodium alginate, hydroxypropyl methyl cellulose O-phthalic One kind in acid esters, hydroxypropyl methyl cellulose acetate, polyacrylic resin, polyvinyl alcohol, polyethylene glycol or chitin or At least two.
- 3. thiabendazolum dry suspensoid agent according to claim 1, it is characterised in that：The wetting glidant is micro mist silicon Glue, lauryl sodium sulfate, dodecyl sodium sulfate, Macrogol 6000, talcum powder, calcium carbonate, magnesium chloride, magnesium hydroxide, Hydrotalcite, magnesium stearate, aluminium hydroxide, starch, one kind in pre-paying starch or at least two.
- 4. thiabendazolum dry suspensoid agent according to claim 1, it is characterised in that：The flavouring for sucrose, glucose, One kind in xylitol, sorbierite, mannitol, lactose, glycyrrhetate, Steviosin, saccharin sodium, aspartame or at least two.
- A kind of 5. preparation method of thiabendazolum dry suspensoid agent according to any one of claims 1 to 4, it is characterised in that：Will After each component is separately dried, ultramicro grinding, crosses 200 mesh sieves, is weighed after mixing according to prescription, packing, you can.
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