CN108295038A - A kind of enteric-coated composition for animals and preparation method thereof - Google Patents
A kind of enteric-coated composition for animals and preparation method thereof Download PDFInfo
- Publication number
- CN108295038A CN108295038A CN201810201203.5A CN201810201203A CN108295038A CN 108295038 A CN108295038 A CN 108295038A CN 201810201203 A CN201810201203 A CN 201810201203A CN 108295038 A CN108295038 A CN 108295038A
- Authority
- CN
- China
- Prior art keywords
- enteric
- coated composition
- animals
- toltrazuril
- bioadhesion
- 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.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 43
- 241001465754 Metazoa Species 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 239000000463 material Substances 0.000 claims abstract description 74
- OCINXEZVIIVXFU-UHFFFAOYSA-N 1-methyl-3-[3-methyl-4-[4-(trifluoromethylthio)phenoxy]phenyl]-1,3,5-triazinane-2,4,6-trione Chemical compound CC1=CC(N2C(N(C)C(=O)NC2=O)=O)=CC=C1OC1=CC=C(SC(F)(F)F)C=C1 OCINXEZVIIVXFU-UHFFFAOYSA-N 0.000 claims abstract description 45
- 229960000898 toltrazuril Drugs 0.000 claims abstract description 45
- 230000035587 bioadhesion Effects 0.000 claims abstract description 25
- 239000002702 enteric coating Substances 0.000 claims abstract description 19
- 238000009505 enteric coating Methods 0.000 claims abstract description 19
- 235000001484 Trigonella foenum graecum Nutrition 0.000 claims description 18
- 244000250129 Trigonella foenum graecum Species 0.000 claims description 18
- 239000000843 powder Substances 0.000 claims description 18
- 235000001019 trigonella foenum-graecum Nutrition 0.000 claims description 18
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims description 14
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 claims description 13
- 238000002156 mixing Methods 0.000 claims description 9
- 239000008118 PEG 6000 Substances 0.000 claims description 8
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 claims description 8
- 239000006185 dispersion Substances 0.000 claims description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 5
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 4
- 210000000936 intestine Anatomy 0.000 claims description 4
- 235000019359 magnesium stearate Nutrition 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 4
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 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 description 2
- 229920001353 Dextrin Polymers 0.000 claims description 2
- 239000004375 Dextrin Substances 0.000 claims description 2
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 235000019425 dextrin Nutrition 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
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- 229960003943 hypromellose Drugs 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- 239000011347 resin Substances 0.000 claims description 2
- 229920005989 resin Polymers 0.000 claims description 2
- 239000000741 silica gel Substances 0.000 claims description 2
- 229910002027 silica gel Inorganic materials 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 238000007907 direct compression Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 24
- 244000144977 poultry Species 0.000 abstract description 24
- 229940079593 drug Drugs 0.000 abstract description 20
- 239000000227 bioadhesive Substances 0.000 abstract description 12
- 238000005516 engineering process Methods 0.000 abstract description 5
- 230000003902 lesion Effects 0.000 abstract description 5
- 230000009471 action Effects 0.000 abstract description 3
- 230000009977 dual effect Effects 0.000 abstract description 2
- 238000013268 sustained release Methods 0.000 abstract description 2
- 239000012730 sustained-release form Substances 0.000 abstract description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 11
- 230000006378 damage Effects 0.000 description 10
- 230000001165 anti-coccidial effect Effects 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 8
- 241000224483 Coccidia Species 0.000 description 6
- 238000012377 drug delivery Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 230000000968 intestinal effect Effects 0.000 description 6
- 210000004347 intestinal mucosa Anatomy 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 244000045947 parasite Species 0.000 description 5
- 210000000813 small intestine Anatomy 0.000 description 5
- 239000004925 Acrylic resin Substances 0.000 description 4
- 229920000178 Acrylic resin Polymers 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 241000522215 Dipteryx odorata Species 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 3
- 230000001070 adhesive effect Effects 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 244000144972 livestock Species 0.000 description 3
- 210000003097 mucus Anatomy 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 210000003250 oocyst Anatomy 0.000 description 3
- 231100000915 pathological change Toxicity 0.000 description 3
- 230000036285 pathological change Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 102000009123 Fibrin Human genes 0.000 description 2
- 108010073385 Fibrin Proteins 0.000 description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 208000030852 Parasitic disease Diseases 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 239000003364 biologic glue Substances 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 229950003499 fibrin Drugs 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 230000003071 parasitic effect Effects 0.000 description 2
- 238000009702 powder compression Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- QMNWYGTWTXOQTP-UHFFFAOYSA-N 1h-triazin-6-one Chemical class O=C1C=CN=NN1 QMNWYGTWTXOQTP-UHFFFAOYSA-N 0.000 description 1
- 206010000060 Abdominal distension Diseases 0.000 description 1
- 241000252983 Caecum Species 0.000 description 1
- 208000003495 Coccidiosis Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 206010022653 Intestinal haemorrhages Diseases 0.000 description 1
- 206010023076 Isosporiasis Diseases 0.000 description 1
- 206010024642 Listless Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000007227 biological adhesion Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000004534 cecum Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003224 coccidiostatic agent Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 235000021050 feed intake Nutrition 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 208000035861 hematochezia Diseases 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000384 rearing effect Effects 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 210000003660 reticulum Anatomy 0.000 description 1
- 210000001563 schizont Anatomy 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- 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
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/736—Glucomannans or galactomannans, e.g. locust bean gum, guar gum
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention provides a kind of enteric-coated composition for animals, including bioadhesion type inner core and enteric outer layer；The bioadhesion type inner core includes Toltrazuril and framework material, adhesion material, and the enteric outer layer includes enteric-coating material；The composition further includes pharmaceutically acceptable auxiliary material.The present invention also provides the preparation methods of the composition, are combined using bioadhesion technology and enteric slow release technology, are prepared for Toltrazuril enteric bioadhesive slow release piece.Enteric-coated composition for animals provided by the invention can go directly lesion, and take and can once rest on the long period in poultry body, there is enteron aisle positioning and bioadhesion dual property, provide enteral sustained release, long action time, stability high enteric-coated composition for animals, medicine frequency is reduced, medication is facilitated.
Description
Technical field
The present invention relates to field of veterinary, and in particular to a kind of enteric-coated composition for animals and preparation method thereof.
Background technology
Globidiosis is a kind of common poultry enteron aisle parasitic protozoa disease, main parasitic chicken, dove, rabbit, pig, dog intestines on
In chrotoplast, organ is digested and assimilated since enteron aisle is important, parasite is proliferated at double leads to the damage of poultry intestinal tissue, intestinal wall
It thickens, specific disease symptom is：Listless, abdominal distension diarrhea, is had blood in stool, spasm even death.Since globidiosis seriously affects fowl
Poultry digests and assimilates feed, and feeding efficiency is made to reduce, and reduces the price of deed, huge economic loss is caused to livestock culture.
And the harm of bigger is, globidiosis infection rate in different types of poultry is up to 60-100%, death rate 50-80%.Especially
It is the area poor in environmental sanitation, and the proliferation spread speed of coccidia is quite surprising, caused infection and death rate higher,
Even full group is annihilated.Globidiosis causes significant damage to animal husbandry, becomes livestock rearing industry and endangers one of maximum parasitic disease.
Toltrazuril category triazineon compounds have wide spectrum coccidiostat activity.It is widely used in globidiosis.Toltrazuril is to ball
The site of action of worm is very extensive, has effect to two asexual cycles of coccidia, such as inhibits schizont, the core point of microgametophyte
It splits and forms body with the wall of microgametophyte.Since this product interferes coccidia nuclear division and mitochondria, breathing and the generation of polypide are influenced
It thanks to function, endocytoplasmic reticulum can be made to expand again in addition, serious ghost occurs, thus with worm effect of killing.
Based on administration for oral administration, current common Toltrazuril oral preparation, active constituent cannot be arrived directly Toltrazuril
Up to lesion, in addition poultry alimentary canal is shorter, digest and assimilate insufficient, bioavilability substantially reduces, and cure rate reduces so that uses
Medicine time lengthening；On the other hand, Toltrazuril poorly water-soluble, is dissolved in unstable, easy precipitation when water, and pulvis with feed
It is not easy to be dispersed in feed in mixed process, and suffers from the poultry intestinal tract injury of globidiosis, food-intake substantially reduces；It is many-sided
Inconvenience, increase difficulty to medication.Therefore it needs one kind that can go directly lesion, and takes and once the long period can rest on fowl
In carcass, to prevent the drug of coccidiosis of livestock and poultry.
Bioadhesive drug delivery system（bioadhesive drug delivery systems,BDDS）It is to utilize material pair
The adhesion property on biological mucosa surface makes drug delivery system in the privileged site increased retention of biomembrane, reaches drug in spy
Determine the purpose of site absorption.This system can adhere to target area, extend drug in the retention time of lesions position, improve it
Treat the effect of topical disorders.But rarer bioadhesive drug delivery system is directed to the research of poultry.Due to the complexity of enteron aisle, make
The effect of bioadhesive drug delivery system and effect variation are very greatly.Poultry alimentary canal is shorter, after needing biological adhesive tablet to enter enteron aisle
Rapid adherency, and suffering from has damage in globidiosis poultry enteron aisle, biological adhesive tablet adhesion strength is too strong further to damage enteron aisle, another
Aspect suffers from globidiosis poultry enteron aisle and generates the even bleeding of more secreting mucus, and the mucus constantly secreted in environment easily shortens life
The adhesion time of object adhesion tablet brings more obstruction to bioadhesion.At present still not for treating being directed to for poultry globidiosis
Property strong bioadhesive drug delivery system research report.
Invention content
The present invention is in view of the above-mentioned problems, a kind of enteric-coated composition for animals of offer and preparation method thereof.
The first purpose of the invention is to provide a kind of enteric-coated composition for animals, the enteric-coated composition for animals includes biology
Adhesive type inner core and enteric outer layer；The bioadhesion type inner core includes Toltrazuril and framework material, adhesion material, the intestines
Molten outer layer includes enteric-coating material；The composition further includes pharmaceutically acceptable auxiliary material；The Toltrazuril, skeleton material
Expect, the mass ratio of adhesion material is（2.0-4.0）：（3.0-6.5）：（1.0-5.5）, the dosage by weight hundred of enteric-coating material
Divide the 2-6% than being calculated as bioadhesion type inner core.Toltrazuril, framework material and adhesion material under this ratio, adhesion property,
Water absorption rate, release are excellent.
Further, the framework material is the mixing of octadecyl alcolol and PEG6000, the matter of the octadecyl alcolol and PEG6000
Measuring ratio is（0.5-2）：（2-5）.Octadecyl alcolol and PEG6000 are melted in this ratio Hybrid Heating, have been merged with Toltrazuril well
Intersolubility, into after poultry enteron aisle, which can keep continuously stable release Toltrazuril, at 48 hours
Interior maintenance effective blood drug concentration.
Further, the adhesion material is one or more in carbopol934, fenugreek gum, hypromellose
Mixture.Fenugreek gum is applied in bioadhesive material by the present invention, and new selection is provided for bioadhesive material.Tonka-bean sheet
There is body analgesic, sterilization, detoxicating, insect-expelling function, gel strength of the fenugreek gum in the alkalescence environment of enteron aisle to stablize, be adhered to
Stablize release Toltrazuril in enteron aisle and also cooperates with expelling parasite with Toltrazuril in addition to adhesive attraction, on the other hand, fenugreek gum
Soluble complex compound can be formed after degradation in vivo with fibrin, the harmful substance accumulated in cleaning enteron aisle helps fowl
Poultry excretes coccidia while treating globidiosis, and treatment poultry globidiosis is with strong points.
Further, since carbopol934 has hydroxyl, amino isopolarity group, water Fast-swelling is met, it is micro- in enteron aisle
It interacts with Toltrazuril in alkaline environment, forms insoluble compound, make Toltrazuril slow release, be jointing material
Preferably selection.But carbopol934 adhesion strengths are strong, due to suffer from globidiosis poultry enteron aisle in have damage even bleeding, merely
Can be too strong because of adhesion strength by adhesion material of carbopol934, further damage intestinal mucosa wall surface.For the problem, this hair
It is bright to provide carbopol934 preferred mixed with fenugreek gum, other than adjusting the effect of adhesion strength, also cooperateed with Toltrazuril
Expelling parasite, while helping to clear up the harmful substance accumulated in enteron aisle.Adherency of the ratio to adhesion tablet of carbopol934, fenugreek gum
Have a significant impact with release, works as carbopol934：The mass ratio of fenugreek gum is（4-6）:（2-3）In range, in bioadhesion type
Core can be with the dissolving of enteric outer layer, and rapid expanding forms network gel structure in enteron aisle, makes moisture infiltration and drug release
Slow down, keeps the release of stablizing of Toltrazuril, meanwhile, for having more muciparous feelings in the poultry enteron aisle for suffering from globidiosis
Condition, remains to the adsorption capacity for having enough, is fully adhered on intestinal mucosa wall and discharges drug, and does not damage intestinal mucosa wall.
Further, the carbopol934：The mass ratio of fenugreek gum is 6:2.5.
Further, the enteric-coating material is acrylic resin soln or ethyl cellulose solution.
Further, the auxiliary material is in magnesium stearate, superfine silica gel powder, talcum powder, lactose, microcrystalline cellulose, dextrin
One or more of mixing.
Second object of the present invention is to provide a kind of preparation method of enteric-coated composition for animals, includes the following steps：
S1：Toltrazuril, framework material, adhesion material, enteric-coating material, auxiliary material are weighed in proportion；
S2：It takes framework material to be melted in 60-90 DEG C of Hybrid Heating, Toltrazuril fine powder is added, stir 1h, be uniformly mixed, it is cooling
It to being fully cured, is ground after being dried under vacuum to moisture 2-3%, crosses 80 mesh sieve and dispersion powders are made；
S3：Adhesion material, auxiliary material are taken, after mixing, is uniformly mixed with dispersion powders equivalent gradually-increased obtained by S2, crosses 40 mesh
Sieve, is added auxiliary material, and bioadhesion type inner core is made in direct powder compression；
S4：Enteric-coating material is prepared, the bioadhesion type core surface obtained by S3 sprays enteric-coating material, dries, and is made
Finished product.
Further, strength of pressed pieces described in S3 is 4-11kN.Preferred strength of pressed pieces is 8 kN.
Further, bioadhesion type inner core diameter 7mm described in S3.
Beneficial effects of the present invention are：
（1）Bioadhesion technology and enteric slow release technology are combined, and the Toltrazuril enteric bioadhesive slow release piece of preparation has
Enteron aisle positions and bioadhesion dual property.Poultry globidiosis diseased region mainly in enteron aisle, selects suitable enteric coat layer
So that adherency inner core is directly reached enteron aisle, active ingredient is made not to be destroyed in hydrochloric acid in gastric juice, can arrive safe and sound and is adhered to focal area
And therapeutic effect is played, and reaching the purpose of " target administration, sustained release ", long action time, stability are high, reduce medicine frequency,
Facilitate medication.
（2）In conjunction with illness poultry gastrointestinal tract feature, to framework material, adhesion material, slow-release material type and match into
Row improves, and obtains the excellent Toltrazuril bioadhesive slow release piece of adhesion property, water absorption rate, release.
（3）It is merged, is ensured after entering poultry enteron aisle, which can protect with Toltrazuril using compound skeleton material
It holds and continuously stablizes release Toltrazuril, maintain effective blood drug concentration for a long time.
（4）Fenugreek gum is applied in bioadhesive material by the present invention, and new selection is provided for bioadhesive material.Tonka-bean
Itself there is analgesic, sterilization, detoxicating, insect-expelling function, gel strength of the fenugreek gum in the alkalescence environment of enteron aisle to stablize, adherency
Stablize release Toltrazuril in enteron aisle and also cooperates with expelling parasite with Toltrazuril in addition to adhesive attraction, on the other hand, tonka-bean
Soluble complex compound can be formed after glue degradation in vivo with fibrin, the harmful substance accumulated in cleaning enteron aisle helps
Poultry excretes coccidia while treating globidiosis, is both adhesion material and medicine, makes this composition to controlling
It is with strong points to treat poultry globidiosis.
（5）The preferred of one compound adhesion material is provided, can be with the dissolving of enteric outer layer, the rapid expanding shape in enteron aisle
Gel structure is reticulated, makes that moisture penetrates into and drug release slows down, keeps the release of stablizing of Toltrazuril, meanwhile, for suffering from ball
There is the case where more secreting mucus in the poultry enteron aisle of parasitosis, remains to the adsorption capacity for having enough, be fully adhered to intestinal mucosa
Drug is discharged on wall, and does not damage intestinal mucosa wall.
Specific implementation mode
Embodiment 1
In mass ratio 2:6:5 ratio weighs Toltrazuril, framework material, adhesion material.Framework material is that mass ratio is 1:3
Octadecyl alcolol and PEG6000, adhesion material are that mass ratio is 5:2 carbopol934 and fenugreek gum, enteric-coating material are propylene
Acid resin solution；Octadecyl alcolol and PEG6000 mixings are taken, is melted in 85 DEG C of Hybrid Heatings, Toltrazuril fine powder is added, stirs 1h,
It is uniformly mixed, is cooled to and is fully cured, ground after being dried under vacuum to moisture 3%, cross 80 mesh sieve and dispersion powders are made；It takes
Carbopol934 and fenugreek gum powder after mixing, are uniformly mixed with dispersion powders equivalent gradually-increased, are crossed 40 mesh sieve, are added 2%
Microcrystalline cellulose and 1.5% magnesium stearate, 8 kN strength of pressed pieces, direct powder compression are made in diameter 7mm bioadhesion types
Core；Enteric-coating material acrylic resin soln is prepared, enteric-coating material, coatings are sprayed in bioadhesion type core surface
Make weightening 3%, dry, present invention enteric-coated composition for animals is made.
Embodiment 2
In mass ratio 3:5:4 ratio weighs Toltrazuril, framework material, adhesion material.Framework material is that mass ratio is 1.5:5
Octadecyl alcolol and PEG6000, adhesion material is fenugreek gum, and enteric-coating material is acrylic resin soln；Take octadecyl alcolol and
PEG6000 mixings are melted in 90 DEG C of Hybrid Heatings, and Toltrazuril fine powder is added, and stir 1h, are uniformly mixed, are cooled to completely solid
Change, ground after being dried under vacuum to moisture 2%, crosses 80 mesh sieve and dispersion powders are made；Fenugreek gum powder is taken, is passed with dispersion powders equivalent
Addition is uniformly mixed, and crosses 40 mesh sieve, 5% microcrystalline cellulose and 0.5% magnesium stearate, 11 kN strength of pressed pieces, powder is added directly to press
Diameter 7mm bioadhesion type inner cores are made in piece method；Enteric-coating material acrylic resin soln is prepared, in bioadhesion type inner core
Surface spraying enteric-coating material, coatings make weightening 2%, drying, and present invention enteric-coated composition for animals is made.
Enteric-coated composition external biological adhesion property for animals experiment prepared by 3 embodiment of the present invention of embodiment
Test method：
1, bioadhesion in vitro is tested：
It takes the rabbit of fasting for 24 hours one, auricular vein to inject air and put to death, takes small intestine, removed with the flushing of pH6.8 phosphate buffers
Content is removed, is cut into small pieces, is put in -20 DEG C of refrigerators and preserves, testing previous night is put in 4 DEG C of refrigerators and thaws, and is placed before testing
To room temperature.
Experiment is divided into 7 groups：1 control group（Toltrazuril ordinary preparation）With 6 experimental groups（Combination prepared by embodiment 1
3 groups of object, 3 groups of composition prepared by embodiment 2）.7 intestinal mucosa are taken to be individually fixed on the thin slice A of 7 setting hooks.Take 1
Toltrazuril ordinary preparation, 3 embodiments 1 prepare composition adherency inner core, and 3 embodiments 2 prepare composition adherency inner core, point
It is not fixed on the thin slice B of 7 setting hooks, thin slice B is hung on holder, adherency core surface 5min is soaked with simulated intestinal fluid
Afterwards, the small intestine on contact thin slice A, and 100g pressure is given, maintain pressure 2min.Certainly by one polybag of hook system on thin slice A
It so hangs down, water is added into polybag with 5ml/min speed, until being detached because pulling force is excessive, weighs thin slice A, polybag and bag
The weight of middle water, as bioadhesion size.The adherency inner core average adhesion that the embodiment of the present invention 1 provides reaches 152.21g/
cm2, embodiment 2 provide adherency inner core average adhesion reach 114.50g/cm2, and the attached power of ordinary tablet is 14.74g/cm2。
2, external adhesion time experiment：
Experiment is divided into 7 groups：1 control group（Toltrazuril ordinary preparation）With 6 experimental groups（Composition 3 prepared by embodiment 1
Group, 3 groups of composition prepared by embodiment 2）.1 Toltrazuril ordinary preparation, 3 embodiments 1 is taken to prepare in composition adherency
Core, 3 embodiments 2 prepare composition adherency inner core, contact, do not applied with mucous membrane of small intestine after soaking 10min with simulated intestinal fluid respectively
Reinforcing, is soaked in simulated intestinal fluid, at room temperature, the time that observation adherency inner core is detached from goldbeater's skin, as adhesion time.
The embodiment of the present invention 1 provide the adherency inner core average adhesion time reach 31h, embodiment 2 provide adherency inner core average adhesion when
Between reach 26h, and ordinary tablet is detached with goldbeater's skin and dispenser immediately.
Experimental result is administered in enteric-coated composition for animals prepared by 4 present invention of embodiment
Experiment is divided into 5 groups：It is real to infect control group, negative control group, Toltrazuril ordinary preparation control group and 1 composition of embodiment
Group, 2 composition experimental group of embodiment are tested, the rabbit that non-ball worm infects is taken to be grouped at random, every group 4.Record experiment precursor respectively
Weight, with the mixing coccidian oocyst peroral infection rabbit with infecting potential.After infection, the daily state of mind for observing each group rabbit,
Feed intake, amount of drinking water, excrement situation, from infecting the 5th day, infection control group, negative control group are not administered, embodiment 1 and implementation
Enteric-coated composition for animals administration 3 times on an empty stomach prepared by example 2（It infects the 5th day, the 7th day, the 9th day each 1 time）, Toltrazuril is common
Preparations. Control group is with 1:100 ratio mixes drug and feed thoroughly continuous use 6 days, the medication of Toltrazuril ordinary preparation last
It, that is, attack after poison the 10th day, each group of weighing rabbit, calculates rate of body weight gain, survival rate, and dissect is all to attack malicious rabbit, takes out enteron aisle, sees
It examines the changing condition of small intestine, caecum, carries out lesion score, pathological changes value is recorded according to score situation, then by small intestine and caecal content
Object is collected respectively, collects egg capsule therein, records the concrete condition of each group experimental rabbit respectively.
Each experimental group is as shown in table 1 to the therapeutic effect of coccidium infection rabbit.
Calculate anticoccidial index（ACI） =（Body weight increase rate+survival rate）×100-（Pathological changes value+oocyst value）.
Anticoccidial index ＞ is efficient anticoccidial drug；Anticoccidial index 160-180 person is middle effect anticoccidial
Medicine；Anticoccidial index 120-160 person is inefficient anticoccidial drug；Anticoccidial index ＜ is invalid anticoccidial drug.
Table 1：Therapeutic effect of each experimental group to coccidium infection rabbit
| Group | Survival rate（%） | Body weight increase rate（%） | Pathological changes value | Oocyst value | ACI |
| Toltrazuril ordinary preparation | 98 | 97.13 | 7.5 | 0 | 187.53 |
| 1 composition of embodiment | 100 | 99.27 | 6.0 | 0 | 193.27 |
| 2 composition of embodiment | 99 | 98.85 | 6.5 | 0 | 191.35 |
| Infection control | 75 | 39.23 | 37.5 | 1 | 75.73 |
| Negative control | 100 | 100 | 0.0 | 0 | 200 |
Experimental result shows, enteric-coated composition for animals prepared by Example 1 and Example 2 of the present invention method, it is only necessary to medicine feed 1 every other day
It is secondary, you can to keep higher blood concentration for a long time in rabbit body, survival rate up to 100%, body weight increase rate up to 99.27%,
ACI mixes the Toltrazuril ordinary preparation control group of daily continuous use thoroughly up to 193.27, higher than by drug and feed, and cuts open and test intestines
Behind road, the case where intestinal bleeding, intestinal wall thicken, is obviously lighter than Toltrazuril ordinary preparation control group, it was demonstrated that fenugreek gum is made except adherency
With outer, expelling parasite is also cooperateed with Toltrazuril, bioavilability is high, and feeding once effectively can prevent, treat globidiosis for a long time.
Claims (10)
1. a kind of enteric-coated composition for animals, which is characterized in that the enteric-coated composition for animals includes bioadhesion type inner core and intestines
Molten outer layer；The bioadhesion type inner core includes that mass ratio is（2.0-4.0）：（3.0-6.5）：（1.0-5.5）Toltrazuril,
Framework material, adhesion material；The enteric outer layer includes enteric-coating material, the dosage by weight hundred of the enteric-coating material
Divide the 2-6% than being calculated as bioadhesion type inner core；The composition further includes pharmaceutically acceptable auxiliary material.
2. a kind of enteric-coated composition for animals according to claim 1, which is characterized in that the framework material is that mass ratio is
（0.5-2）：（2-5）Octadecyl alcolol and PEG6000.
3. a kind of enteric-coated composition for animals according to claim 1, which is characterized in that the adhesion material is
One or more mixture in carbopol934, fenugreek gum, hypromellose.
4. a kind of enteric-coated composition for animals according to claim 3, which is characterized in that the adhesion material is mass ratio
（4-6）:（2-3）Carbopol934 and fenugreek gum.
5. a kind of enteric-coated composition for animals according to claim 3, which is characterized in that the adhesion material is mass ratio 6:
2.5 carbopol934 and fenugreek gum.
6. a kind of enteric-coated composition for animals according to claim 1, which is characterized in that the enteric-coating material is propylene
Acid resin solution or ethyl cellulose solution.
7. a kind of enteric-coated composition for animals according to claim 1, which is characterized in that the auxiliary material is magnesium stearate, micro-
The mixing of one or more of powder silica gel, talcum powder, lactose, microcrystalline cellulose, dextrin.
8. a kind of preparation method of enteric-coated composition for animals of claim 1 to 7 any one of them, which is characterized in that including with
Lower step：
S1：Toltrazuril, framework material, adhesion material, enteric-coating material, auxiliary material are weighed in proportion；
S2：It takes framework material to be melted in 60-90 DEG C of Hybrid Heating, Toltrazuril fine powder is added, stir 1h, be uniformly mixed, it is cooling
It to being fully cured, is ground after being dried under vacuum to moisture 2-3%, crosses 80 mesh sieve and dispersion powders are made；
S3：It takes adhesion material to be uniformly mixed with dispersion powders equivalent gradually-increased obtained by S2, crosses 40 mesh sieve, add auxiliary materials and mixing, powder
Bioadhesion type inner core is made in direct compression method；
S4：Enteric-coating material is prepared, the bioadhesion type core surface obtained by S3 sprays enteric-coating material, dries, and is made
Finished product.
9. preparation method according to claim 8, which is characterized in that strength of pressed pieces described in S3 is 4-11kN.
10. preparation method according to claim 8, which is characterized in that bioadhesion type inner core diameter 7mm described in S3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810201203.5A CN108295038B (en) | 2018-03-12 | 2018-03-12 | Veterinary enteric composition and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810201203.5A CN108295038B (en) | 2018-03-12 | 2018-03-12 | Veterinary enteric composition and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108295038A true CN108295038A (en) | 2018-07-20 |
| CN108295038B CN108295038B (en) | 2020-08-28 |
Family
ID=62849684
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810201203.5A Active CN108295038B (en) | 2018-03-12 | 2018-03-12 | Veterinary enteric composition and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108295038B (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6004585A (en) * | 1996-02-05 | 1999-12-21 | Bayer Aktiengesellschaft | Granular composition of a triazine compound |
| CN1331561A (en) * | 1998-10-08 | 2002-01-16 | 高新研究公司 | Novel compsns. and methods for prevention and treatment of protozoal disease |
| CN101491497A (en) * | 2008-12-26 | 2009-07-29 | 天津瑞普生物技术股份有限公司 | Toltrazuril suspension preparation capable of being effectively uniformly dispersed in water and preparation method thereof |
| BRPI0901058A2 (en) * | 2008-03-19 | 2009-11-03 | Adolfo Augusto Aubinel | oral bioadhesive formulation based on triazine-derived compounds and the procedure for obtaining it |
| CN103070844A (en) * | 2013-01-28 | 2013-05-01 | 万平 | Locating quick-release biological adhesive and application thereof |
| CN103083272A (en) * | 2013-01-22 | 2013-05-08 | 上海应用技术学院 | Levetiracetam bioadhesive sustained-release tablet and preparation method thereof |
-
2018
- 2018-03-12 CN CN201810201203.5A patent/CN108295038B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6004585A (en) * | 1996-02-05 | 1999-12-21 | Bayer Aktiengesellschaft | Granular composition of a triazine compound |
| CN1331561A (en) * | 1998-10-08 | 2002-01-16 | 高新研究公司 | Novel compsns. and methods for prevention and treatment of protozoal disease |
| BRPI0901058A2 (en) * | 2008-03-19 | 2009-11-03 | Adolfo Augusto Aubinel | oral bioadhesive formulation based on triazine-derived compounds and the procedure for obtaining it |
| CN101491497A (en) * | 2008-12-26 | 2009-07-29 | 天津瑞普生物技术股份有限公司 | Toltrazuril suspension preparation capable of being effectively uniformly dispersed in water and preparation method thereof |
| CN103083272A (en) * | 2013-01-22 | 2013-05-08 | 上海应用技术学院 | Levetiracetam bioadhesive sustained-release tablet and preparation method thereof |
| CN103070844A (en) * | 2013-01-28 | 2013-05-01 | 万平 | Locating quick-release biological adhesive and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 符华林等: "地克珠利肠溶微囊的制备及其特性的研究", 《中国兽医科学》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108295038B (en) | 2020-08-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20190328659A1 (en) | Elastic sheet with function of re-activating endometrial basal layer in uterine cavity and forming method thereof | |
| JP2002513418A (en) | Therapeutically active composition | |
| AU2014305430B2 (en) | Application of andrographolide in the preparation of a pharmaceutical for treatment of inflammatory bowel disease, andrographolide enteric targeting micropellet, and method for preparation thereof | |
| CN101690717A (en) | Valnemulin for livestock and saline premix and preparation method thereof | |
| CN201426856Y (en) | Tilmicosin enteric coated granule | |
| CN101099730A (en) | Oral solid preparation containing ambroxol hydrochloride and guaifenesin active components | |
| CN108295038A (en) | A kind of enteric-coated composition for animals and preparation method thereof | |
| CN114053251A (en) | Sulfated polysaccharide inhalation preparation and application thereof in preventing and treating new coronavirus related diseases | |
| CN103494792B (en) | Compound phloroglucinol freeze-dried orally-disintegrating tablet and preparation method | |
| US20110091536A1 (en) | Compositions comprising euphorbia prostrata and process of preparation thereof | |
| CN105169107A (en) | Anti-depression dispersible traditional Chinese medicine tablet | |
| CN109453192A (en) | A kind of compound hydrochloric acid terramycin alumen borneol effervescent tablet and preparation method thereof | |
| CN109432219A (en) | A kind of thiosugar aluminium porcelain enamelling | |
| CN102727420B (en) | D-glutamyl-D-tryptophan sodium colon targeting drug delivery agent and preparation method thereof | |
| CN100360120C (en) | Application of fenugreek total alkali extract in preparing medicine for ulcerative colitis and preparation method of colon targeted preparation | |
| CN105055700A (en) | Rheumatic arthritis plaster and preparation method thereof | |
| CN101966197A (en) | Composition for treating bovine severe compound parasitic infection and preparation method thereof | |
| CN112353774B (en) | Nascitide flavor chewable tablet, preparation method thereof and application thereof to clostridium welchii disease of dog | |
| CN105012348A (en) | Bioactive vaginal suppository containing growth factors | |
| CN104434992A (en) | Biological adhesive vaginal tablet of periplaneta americana extract and preparation method of biological adhesive vaginal tablet | |
| US20170354678A1 (en) | Use of the mixture of a salt and sugar in the manufacture of a medicament employed for treating Lax vagina syndrome or colpoxerosis disease in an mammal | |
| CN113041213B (en) | Rectal suppository containing hyaluronic acid and tetrahydropyrimidine and preparation method thereof | |
| Singh et al. | Lameness in cattle-A review | |
| CN105832896B (en) | A kind of Chinese medicine for treating cervicitis and preparation method thereof, application | |
| CN107050393A (en) | Numbness of relaxing dispersing paste and preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A veterinary enteric composition and its preparation method Granted publication date: 20200828 Pledgee: Bank of Nanjing Co.,Ltd. Changzhou Branch Pledgor: JIANGSU LINGYUN PHARMACEUTICAL CO.,LTD. Registration number: Y2024980019202 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right |