CN106420622A - Tilmicosin submicron powder water soluble preparation and preparing method thereof - Google Patents
Tilmicosin submicron powder water soluble preparation and preparing method thereof Download PDFInfo
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- CN106420622A CN106420622A CN201610947110.8A CN201610947110A CN106420622A CN 106420622 A CN106420622 A CN 106420622A CN 201610947110 A CN201610947110 A CN 201610947110A CN 106420622 A CN106420622 A CN 106420622A
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- Prior art keywords
- tilmicosin
- preparation
- water
- superfine powder
- soluble preparation
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- 238000002360 preparation method Methods 0.000 title claims abstract description 95
- 229960000223 tilmicosin Drugs 0.000 title claims abstract description 90
- JTSDBFGMPLKDCD-XVFHVFLVSA-N tilmicosin Chemical compound O([C@@H]1[C@@H](C)[C@H](O)CC(=O)O[C@@H]([C@H](/C=C(\C)/C=C/C(=O)[C@H](C)C[C@@H]1CCN1C[C@H](C)C[C@H](C)C1)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@@H]1O[C@H](C)[C@@H](O)[C@H](N(C)C)[C@H]1O JTSDBFGMPLKDCD-XVFHVFLVSA-N 0.000 title claims abstract description 90
- 239000000843 powder Substances 0.000 title claims abstract description 62
- 238000000034 method Methods 0.000 title abstract description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title abstract description 11
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims abstract description 27
- 229920000053 polysorbate 80 Polymers 0.000 claims abstract description 27
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims abstract description 25
- 229930064664 L-arginine Natural products 0.000 claims abstract description 25
- 235000014852 L-arginine Nutrition 0.000 claims abstract description 25
- 239000000463 material Substances 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 13
- 239000002699 waste material Substances 0.000 claims description 8
- NTNWOCRCBQPEKQ-YFKPBYRVSA-N N(omega)-methyl-L-arginine Chemical compound CN=C(N)NCCC[C@H](N)C(O)=O NTNWOCRCBQPEKQ-YFKPBYRVSA-N 0.000 claims description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 abstract description 17
- 239000008118 PEG 6000 Substances 0.000 abstract description 14
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 abstract description 14
- 239000003814 drug Substances 0.000 abstract description 8
- 239000012535 impurity Substances 0.000 abstract description 8
- 230000007774 longterm Effects 0.000 abstract description 4
- 230000001225 therapeutic effect Effects 0.000 abstract description 4
- 230000001133 acceleration Effects 0.000 abstract description 3
- 238000004090 dissolution Methods 0.000 abstract description 2
- 208000023504 respiratory system disease Diseases 0.000 abstract description 2
- 238000007689 inspection Methods 0.000 abstract 1
- 230000003285 pharmacodynamic effect Effects 0.000 abstract 1
- 239000004552 water soluble powder Substances 0.000 abstract 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 12
- 241000287828 Gallus gallus Species 0.000 description 10
- 241000209094 Oryza Species 0.000 description 7
- 235000007164 Oryza sativa Nutrition 0.000 description 7
- 239000003094 microcapsule Substances 0.000 description 7
- 235000009566 rice Nutrition 0.000 description 7
- -1 PVPK30 Chemical compound 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 230000000844 anti-bacterial effect Effects 0.000 description 5
- 230000036528 appetite Effects 0.000 description 4
- 235000019789 appetite Nutrition 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 241000204031 Mycoplasma Species 0.000 description 3
- 241000193830 Bacillus <bacterium> Species 0.000 description 2
- 206010034107 Pasteurella infections Diseases 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 208000018569 Respiratory Tract disease Diseases 0.000 description 2
- 229930194936 Tylosin Natural products 0.000 description 2
- 239000004182 Tylosin Substances 0.000 description 2
- 239000005030 aluminium foil Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 201000005115 pasteurellosis Diseases 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 229960004059 tylosin Drugs 0.000 description 2
- WBPYTXDJUQJLPQ-VMXQISHHSA-N tylosin Chemical compound O([C@@H]1[C@@H](C)O[C@H]([C@@H]([C@H]1N(C)C)O)O[C@@H]1[C@@H](C)[C@H](O)CC(=O)O[C@@H]([C@H](/C=C(\C)/C=C/C(=O)[C@H](C)C[C@@H]1CC=O)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@H]1C[C@@](C)(O)[C@@H](O)[C@H](C)O1 WBPYTXDJUQJLPQ-VMXQISHHSA-N 0.000 description 2
- 235000019375 tylosin Nutrition 0.000 description 2
- 239000000273 veterinary drug Substances 0.000 description 2
- NESIVXZOSKKUDP-ARVJLQODSA-N (4r,5s,6s,7r,9r,11e,13e,15r,16r)-6-[(2r,3r,4s,5s,6r)-4-(dimethylamino)-3,5-dihydroxy-6-methyloxan-2-yl]oxy-7-[2-[(3s,5r)-3,5-dimethylpiperidin-1-yl]ethyl]-16-ethyl-4-hydroxy-15-[[(2r,3r,4r,5r,6r)-5-hydroxy-3,4-dimethoxy-6-methyloxan-2-yl]oxymethyl]-5,9,13 Chemical compound OP(O)(O)=O.O([C@@H]1[C@@H](C)[C@H](O)CC(=O)O[C@@H]([C@H](/C=C(\C)/C=C/C(=O)[C@H](C)C[C@@H]1CCN1C[C@H](C)C[C@H](C)C1)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@@H]1O[C@H](C)[C@@H](O)[C@H](N(C)C)[C@H]1O NESIVXZOSKKUDP-ARVJLQODSA-N 0.000 description 1
- IDWRJRPUIXRFRX-UHFFFAOYSA-N 3,5-dimethylpiperidine Chemical compound CC1CNCC(C)C1 IDWRJRPUIXRFRX-UHFFFAOYSA-N 0.000 description 1
- 241000606750 Actinobacillus Species 0.000 description 1
- 241000186046 Actinomyces Species 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001430197 Mollicutes Species 0.000 description 1
- 206010028470 Mycoplasma infections Diseases 0.000 description 1
- 241000202934 Mycoplasma pneumoniae Species 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 208000007893 Salpingitis Diseases 0.000 description 1
- 241000605008 Spirillum Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 238000009360 aquaculture Methods 0.000 description 1
- 244000144974 aquaculture Species 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 239000003640 drug residue Substances 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 208000004396 mastitis Diseases 0.000 description 1
- 238000004137 mechanical activation Methods 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 201000006509 pleuropneumonia Diseases 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 235000015096 spirit Nutrition 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 229960000757 tilmicosin phosphate Drugs 0.000 description 1
- 238000011179 visual inspection Methods 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K9/145—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 compounds
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a tilmicosin submicron powder water soluble preparation and a preparing method thereof, and belongs to the technical field of veterinary medicine preparing. The tilmicosin submicron powder water soluble preparation is soluble powder. The tilmicosin submicron powder water soluble preparation is prepared from, by mass, 15%-35% tilmicosin, 15%-35% PVPK30, 15-35% of PEG6000, 5%-20% L-arginine and 1%-5% Tween-80. The tilmicosin submicron powder water soluble preparation does not degrade, specific surface area is increased, the preparation can be well dispersed and easier to be absorbed, the dissolution rate of the tilmicosin is greatly increased, and the preparation has low moisture and few impurities. An acceleration test and long-term test inspection show that the preparation has good stability. A pharmacodynamic test is conducted on the prepared tilmicosin submicron powder water soluble preparation and finds that therapeutic effect for respiratory disease of the preparation is significantly higher than that of ordinary tilmicosin water soluble powder, the cure rate reaches up to 89.6%, and the effective rate reaches up to 94.6%.
Description
Technical field
The invention belongs to veterinary drug technical field is and in particular to a kind of formula of the water-soluble preparation of tilmicosin superfine powder and its system
Preparation Method.
Background technology
In recent years, abuse of antibiotics phenomenon is very universal, and bacterial resistance problem is on the rise, in order to treatment of animals, resist
Raw element generally will add several times amount and can be only achieved certain curative effect, the use of the antibiotic of heavy dose, lead to medicine in animal body no
Method metabolism is just excreted completely, causes to water source, second pollution of the environment such as soil.In order to prevent and treat Animal diseases, promote
Enter aquaculture to develop in a healthy way, safeguard health, reduce the excretion of drug residue as far as possible.Clinically it is badly in need of dosage few, medicine
Thing metabolism is fast and determined curative effect, and the antibacterials of safety are supplementing or to substitute.
Tilmicosin is the special antibiotic of semi-synthetic Macrolide poultry of the exploitation eighties in 20th century, is by tylosin
Plain reaction with 3,5- lupetidine generates tilmicosin alkali, then the acid that phosphorates forms tilmicosin phosphate with water, and it is along instead
The mixture of isomer.All there is inhibitory action to gram positive bacteria, some gram negative bacterias, mycoplasma, spirillum etc., right
Pleuropneumonia actinomyces, pasteurellosis bacilluss have the antibacterial activity more higher than tylosin.It is mainly used in preventing and treating domestic animal pneumonia (by breast
Film Actinobacillus, pasteurellosis bacilluss, mycoplasma etc. infection cause), avian mycoplasmas disease and lactating mammal mastitis.
But, the tilmicosin veterinary drug preparation dissolubility that prior art produces is poor, and poisonous side effect of medicine is big, and stability is poor,
Drug dose is big, and slow grade of metabolism easily causes second pollution to environment.
Content of the invention
In order to overcome defect present in above-mentioned prior art, it is an object of the invention to provide a kind of tilmicosin ultra micro
Water-soluble preparation of powder and preparation method thereof, the method adopts low-temperature airflow to process, simple to operate, low for equipment requirements；Through the method
The water-soluble better stability of preparation of prepared tilmicosin superfine powder, dissolubility is good, and moisture is low, and impurity is few, and dosage is few, metabolism
Hurry up.
The present invention is to be achieved through the following technical solutions：
The invention discloses a kind of water-soluble preparation of tilmicosin superfine powder, by percentage to the quality, including：15%～35%
Tilmicosin, 15%～35% PVPK30,15%～35% PEG6000,5%～20% L-Arginine, 1%～
5% tween 80.
Preferably, the water-soluble preparation of tilmicosin superfine powder of the present invention, by percentage to the quality, including：20%～30%
Tilmicosin, 20%～30% PVPK30,20%～30% PEG6000,8%～17% L-Arginine, 2%～
4% tween 80.
Preferably, the water-soluble preparation of tilmicosin superfine powder of the present invention, by percentage to the quality, including：25% for rice
Examine star, 30% PVPK30,30% PEG6000,12% L-Arginine, 3% tween 80.
The invention also discloses a kind of preparation method of the water-soluble preparation of tilmicosin superfine powder, comprise the following steps：
1) by percentage to the quality, take supplementary material：15%～35% tilmicosin, 15%～35% PVPK30,
15%～35% PEG6000,5%～20% L-Arginine, 1%～5% tween 80, standby；
2) by step 1) described in supplementary material adopt mixer, be sufficiently mixed uniformly；
3) material of mix homogeneously is entered grader by drawing-in device to be processed, be that the material particular diameter after processing is
0.2～25 μm, the water-soluble preparation of prepared tilmicosin superfine powder.
Preferably, step 2) in, the uniformly time used that is sufficiently mixed is 30～60min.
Preferably, step 3) in, the intake air temperature of grader controls at -15～20 DEG C, Stress control 0.5～
1.0MPa, FREQUENCY CONTROL is in 15～45Hz.
The air-flow entering grader will be through moisture solution and oily waste treatment.
Compared with prior art, the present invention has following beneficial technique effect：
The water-soluble preparation of tilmicosin superfine powder disclosed by the invention, the every kind of component in formula is all screened meticulously through overtesting
, PVPK30 can play stably dispersing control particle diameter effect, animal for animals in the last few years respiratory tract disease generation except
Antibacterial, also much virus causes, and usually from mixed infection therefore adds a certain proportion of L-Arginine in this formula, makes
Obtain the effect that this product also has antiviral except having antibacterial action, PEG6000 is mainly to increase the dissolubility of tilmicosin,
Several composition advantageous combination also can increase the antivirus action of tilmicosin micro-capsule preparation except the dissolubility that meeting increases tilmicosin.Should
The water-soluble preparation of superfine powder adopts low temperature process to be obtained, and particle diameter is 0.2～25 μm；The water-soluble preparation of this superfine powder is non-degradable, specific surface area
Increase, can preferably disperse to be substantially increased dissolubility and the dissolution rate of tilmicosin it is easier to absorb, its moisture is low, miscellaneous
Matter is few, dosage few (less than 2/3rds of general preparation), and drug metabolism is fast.Accelerated test and long term test are investigated, and show
Show that it possesses good stability.The water-soluble preparation of tilmicosin superfine powder that the present invention is obtained carries out the test of pesticide effectiveness, finds it
To the therapeutic effect of respiratory tract disease apparently higher than common tilmicosin soluble powder, cure rate reaches 89.6%, and effective percentage reaches
94.6%.
The water-soluble formulation preparation method of tilmicosin superfine powder disclosed by the invention, rationally, preparation technology adopts formula composition
Low-temperature airflow is processed, simple to operate, low for equipment requirements, the solid dispersion made compared to existing process, and it is coated technique
And mechanical activation comminution is simpler, stable, easily operates, be more suitable for producing greatly, the anti-degraded than the average airflow mach preparation of pulverizing
Performance is higher.
Specific embodiment
With reference to specific embodiment, the present invention is described in further detail, described be explanation of the invention and
It is not to limit.
Embodiment 1
A kind of low-temperature airflow processes the water-soluble preparation of tilmicosin superfine powder, by percentage to the quality, including 25% for rice
Examine star, 30% PVPK30,30% PEG6000,12% L-Arginine, 3% tween 80.
The preparation method of this water-soluble preparation of tilmicosin superfine powder is as follows：
Step 1：Account for superfine powder water-soluble quality of the pharmaceutical preparations percentage ratio 25% according to tilmicosin, PVPK30 accounts for this water-soluble preparation matter
The 30% of amount percentage ratio, PEG6000 accounts for the 30% of this water-soluble quality of the pharmaceutical preparations percentage ratio, L-Arginine and accounts for the percent mass of said preparation
The 12% of ratio, tween 80 account for the standard of the 3% of the mass percent of said preparation come to weigh tilmicosin, PVPK30, PEG6000,
L-Arginine, Tween 80 are as standby.
Step 2：The supplementary material weighing is placed in mixer, mixes 30～60 minutes.
Step 3：The material of mix homogeneously is entered grader by drawing-in device process.Grader intake air temperature controls
At -15～20 degree, Stress control 0.5～1.0, is classified unit frequency and is adjusted to 15～45HZ.The air-flow entering grader will pass through
Moisture solution and oily waste treatment.The tilmicosin micro-capsule preparation fine work moisture that material is made after staged care is low, and impurity contains
Amount is low, and stability is high.Material particular diameter is：0.2～25um.
Embodiment 2
A kind of low-temperature airflow processes the water-soluble preparation of tilmicosin superfine powder, by percentage to the quality, including 30% for rice
Examine star, 25% PVPK30,30% PEG6000,14% L-Arginine, 1% Tween 80.
The preparation method of this water-soluble preparation of tilmicosin superfine powder is as follows：
Step 1：Account for superfine powder water-soluble quality of the pharmaceutical preparations percentage ratio 30% according to tilmicosin, PVPK30 accounts for this water-soluble preparation matter
The 25% of amount percentage ratio, PEG6000 accounts for the 30% of this water-soluble quality of the pharmaceutical preparations percentage ratio, L-Arginine and accounts for the percent mass of said preparation
The 14% of ratio, tween 80 account for the standard of the 1% of the mass percent of said preparation come to weigh tilmicosin, PVPK30, PEG6000,
L-Arginine, Tween 80 are as standby.
Step 2：The supplementary material weighing is placed in mixer, mixes 30～60 minutes.
Step 3：The material of mix homogeneously is entered grader by drawing-in device process.Grader intake air temperature controls
At -15～20 degree, Stress control 0.5～1.0, is classified unit frequency and is adjusted to 15～45HZ.The air-flow entering grader will pass through
Moisture solution and oily waste treatment.The tilmicosin micro-capsule preparation moisture that material is made after staged care is low, and impurity content is low,
Stability is high.Material particular diameter is：0.2～25um.
Embodiment 3
A kind of low-temperature airflow processes the water-soluble preparation of tilmicosin superfine powder, by percentage to the quality, including 29% for rice
Examine star, 26% PVPK30,30% PEG6000,13% L-Arginine, 2% Tween 80.
The preparation method of this water-soluble preparation of tilmicosin superfine powder is as follows：
Step 1：Account for superfine powder water-soluble quality of the pharmaceutical preparations percentage ratio 29% according to tilmicosin, PVPK30 accounts for this water-soluble preparation matter
The 26% of amount percentage ratio, PEG6000 accounts for the 30% of this water-soluble quality of the pharmaceutical preparations percentage ratio, L-Arginine and accounts for the percent mass of said preparation
The 13% of ratio, tween 80 account for the standard of the 2% of the mass percent of said preparation come to weigh tilmicosin, PVPK30, PEG6000,
L-Arginine, Tween 80 are as standby.
Step 2：The supplementary material weighing is placed in mixer, mixes 30～60 minutes.
Step 3：The material of mix homogeneously is entered grader by drawing-in device process.Grader intake air temperature controls
At -15～20 degree, Stress control 0.5～1.0, is classified unit frequency and is adjusted to 15～45HZ.The air-flow entering grader will pass through
Moisture solution and oily waste treatment.The tilmicosin micro-capsule preparation moisture that material is made after staged care is low, and impurity content is low,
Stability is high.Material particular diameter is：0.2～25um.
Embodiment 4
A kind of low-temperature airflow processes the water-soluble preparation of tilmicosin superfine powder, by percentage to the quality, including 30% for rice
Examine star, 25% PVPK30,25% PEG6000,15% L-Arginine, 5% Tween 80.
The preparation method of this water-soluble preparation of tilmicosin superfine powder is as follows：
Step 1：Account for superfine powder water-soluble quality of the pharmaceutical preparations percentage ratio 30% according to tilmicosin, PVPK30 accounts for this water-soluble preparation matter
The 25% of amount percentage ratio, PEG6000 accounts for the 25% of this water-soluble quality of the pharmaceutical preparations percentage ratio, L-Arginine and accounts for the percent mass of said preparation
The 15% of ratio, tween 80 account for the standard of the 5% of the mass percent of said preparation come to weigh tilmicosin, PVPK30, PEG6000,
L-Arginine, Tween 80 are as standby.
Step 2：The supplementary material weighing is placed in mixer, mixes 30～60 minutes.
Step 3：The material of mix homogeneously is entered grader by drawing-in device process.Grader intake air temperature controls
At -15～20 degree, Stress control 0.5～1.0, is classified unit frequency and is adjusted to 15～45HZ.The air-flow entering grader will pass through
Moisture solution and oily waste treatment.The tilmicosin micro-capsule preparation moisture that material is made after staged care is low, and impurity content is low,
Stability is high.Material particular diameter is：0.2～25um.
Embodiment 5
A kind of low-temperature airflow processes the water-soluble preparation of tilmicosin superfine powder, by percentage to the quality, including 20% for rice
Examine star, 30% PVPK30,35% PEG6000,12% L-Arginine, 3% Tween 80.
The preparation method of this water-soluble preparation of tilmicosin superfine powder is as follows：
Step 1：Account for superfine powder water-soluble quality of the pharmaceutical preparations percentage ratio 20% according to tilmicosin, PVPK30 accounts for this water-soluble preparation matter
The 30% of amount percentage ratio, PEG6000 accounts for the 35% of this water-soluble quality of the pharmaceutical preparations percentage ratio, L-Arginine and accounts for the percent mass of said preparation
The 12% of ratio, tween 80 account for the standard of the 3% of the mass percent of said preparation come to weigh tilmicosin, PVPK30, PEG6000,
L-Arginine, Tween 80 are as standby.
Step 2：The supplementary material weighing is placed in mixer, mixes 30～60 minutes.
Step 3：The material of mix homogeneously is entered grader by drawing-in device process.Grader intake air temperature controls
At -15～20 degree, Stress control 0.5～1.0, is classified unit frequency and is adjusted to 15～45HZ.The air-flow entering grader will pass through
Moisture solution and oily waste treatment.The tilmicosin micro-capsule preparation moisture that material is made after staged care is low, and impurity content is low,
Stability is high.Material particular diameter is：0.2～25um.
Embodiment 6
A kind of low-temperature airflow processes the water-soluble preparation of tilmicosin superfine powder, by percentage to the quality, including 30% for rice
Examine star, 30% PVPK30,20% PEG6000,17% L-Arginine, 3% Tween 80.
The preparation method of this water-soluble preparation of tilmicosin superfine powder is as follows：
Step 1：Account for superfine powder water-soluble quality of the pharmaceutical preparations percentage ratio 30% according to tilmicosin, PVPK30 accounts for this water-soluble preparation matter
The 30% of amount percentage ratio, PEG6000 accounts for the 20% of this water-soluble quality of the pharmaceutical preparations percentage ratio, L-Arginine and accounts for the percent mass of said preparation
The 17% of ratio, tween 80 account for the standard of the 3% of the mass percent of said preparation come to weigh tilmicosin, PVPK30, PEG6000,
L-Arginine, Tween 80 are as standby.
Step 2：The supplementary material weighing is placed in mixer, mixes 30～60 minutes.
Step 3：The material of mix homogeneously is entered grader by drawing-in device process.Grader intake air temperature controls
At -15～20 degree, Stress control 0.5～1.0, is classified unit frequency and is adjusted to 15～45HZ.The air-flow entering grader will pass through
Moisture solution and oily waste treatment.The tilmicosin micro-capsule preparation moisture that material is made after staged care is low, and impurity content is low,
Stability is high.Material particular diameter is：0.2～25um.
The tilmicosin superfine powder that embodiments of the invention 1 arrive obtained in embodiment 6 is white or off-white powder.
Stablizing of the tilmicosin superfine powder that embodiment 1 obtains in embodiment 6 is investigated using accelerated test, long term test
Property.Test finds that it has good stability, specific as follows：
(1) accelerated test：The tilmicosin superfine powder that 3 crowdes of present invention are obtained is sealed in aluminium foil bag, in (40 ± 2)
DEG C, place 6 months under the conditions of relative humidity (75 ± 5) %, sample when 1,2,3,6 the end of month, by study on the stability item
Visual inspection is surveyed, and checks character, measures the content of tilmicosin.It is found that under acceleration environment, the character of tilmicosin is unchanged, content
Stable.
(2) long term test：The tilmicosin superfine powder that 3 crowdes of present invention are obtained is sealed in aluminium foil bag, in (30 ± 2)
DEG C, place 12 months under the conditions of relative humidity (65 ± 5) %, sample when 0,3,6,9,12 the end of month, examine by stability
Examine item detection, check character, measure the content of tilmicosin.It is found that under acceleration environment, the property of tilmicosin superfine powder
Shape is unchanged, stable content.
The water-soluble preparation of tilmicosin superfine powder that the present invention is obtained is mainly used in the treatment of bacterial disease, real producing
It is used for the treatment of mycoplasma pneumoniae in border.Usage：In terms of this product.For oral administration：One secondary amounts, every 1kg body weight, chicken 0.05～0.1g, one
Day 2 times, it is used in conjunction 5；Mixed drink：Every 1L water, chicken 0.17g, it is used in conjunction 3～5.
The water-soluble preparation of tilmicosin superfine powder that the present invention is obtained carries out the test of pesticide effectiveness, as follows：
The chicken of respiratory tract antibacterial and mycoplasma infection 1000, is randomly divided into 2 groups, every group 500, and wherein A group is ultralow
The tilmicosin superfine powder water-soluble preparation group of temperature preparation, in drinking-water, addition is every 1L water, and chicken 0.17g is used in conjunction 3～5.B group
For common tilmicosin soluble powder group, mix drink：Every 1L water, chicken 0.17g, it is used in conjunction 3～5.
The therapeutic effect to Chicken salpingitis for the water-soluble preparation of tilmicosin superfine powder
During test, the clinical symptoms such as the spirit of main detection chicken, respiratory symptom, appetite, feces.Spiritual after medication,
Appetite, observe situations such as lay eggs.Medication clinical symptom disappearance is recovery from illness；Food increases and is intended to, in high spirits switchs to effectively；Produce after medication
Egg, appetite, spirit do not improve in addition increase or dead for invalid.Calculate cure rate, effective percentage and mortality rate：
After the water-soluble preparation for treating of tilmicosin superfine powder, the ill chicken mental status is clearly better, and respiratory tract sounds disappear,
Appetite increase, continuous use after 7 days chicken group's respiratory symptom substantially mitigate, tilmicosin superfine powder water-soluble preparation group cure rate
89.6%, effective percentage 94.6%, mortality rate 1.6%, with matched group significant difference (P<0.05) (table 1).
The therapeutic effect to respiratory disease of chicken for the water-soluble preparation of table 1 tilmicosin superfine powder
Claims (7)
1. a kind of water-soluble preparation of tilmicosin superfine powder is it is characterised in that by percentage to the quality, including：15%～35%
Tilmicosin, 15%～35% PVPK30,15%～35% PEG6000,5%～20% L-Arginine, 1%～5%
Tween 80.
2. the water-soluble preparation of tilmicosin superfine powder according to claim 1 it is characterised in that by percentage to the quality, bag
Include：20%～30% tilmicosin, 20%～30% PVPK30,20%～30% PEG6000,8%～17% L-
Arginine, 2%～4% tween 80.
3. the water-soluble preparation of tilmicosin superfine powder according to claim 1 it is characterised in that by percentage to the quality, bag
Include：25% tilmicosin, 30% PVPK30,30% PEG6000,12% L-Arginine, 3% tween 80.
4. a kind of preparation method of the water-soluble preparation of tilmicosin superfine powder is it is characterised in that comprise the following steps：
1) by percentage to the quality, take supplementary material：15%～35% tilmicosin, 15%～35% PVPK30,15%～
35% PEG6000,5%～20% L-Arginine, 1%～5% tween 80, standby；
2) by step 1) described in supplementary material adopt mixer, be sufficiently mixed uniformly；
3) material of mix homogeneously is entered grader by drawing-in device to be processed, be that the material particular diameter after processing is 0.2
～25 μm, the water-soluble preparation of prepared tilmicosin superfine powder.
5. the preparation method of the water-soluble preparation of tilmicosin superfine powder according to claim 4 is it is characterised in that step 2)
In, the uniformly time used that is sufficiently mixed is 30～60min.
6. the preparation method of the water-soluble preparation of tilmicosin superfine powder according to claim 4 is it is characterised in that step 3)
In, the intake air temperature of grader controls at -15～20 DEG C, and, in 0.5～1.0MPa, FREQUENCY CONTROL is in 15～45Hz for Stress control.
7. the preparation method of the water-soluble preparation of tilmicosin superfine powder according to claim 6 is it is characterised in that enter classification
The air-flow of machine will be through moisture solution and oily waste treatment.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107853465A (en) * | 2017-11-06 | 2018-03-30 | 四川恒通动保生物科技有限公司 | A kind of pellet pre-mixing agent and preparation method thereof |
| CN110478321A (en) * | 2019-09-16 | 2019-11-22 | 四川恒通动物制药有限公司 | A kind of veterinary drug soluble powder that can be mixed thoroughly with pellet |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670516A (en) * | 2012-05-29 | 2012-09-19 | 广东大华农动物保健品股份有限公司 | Tilmicosin soluble powder and preparation method thereof |
| CN104473876A (en) * | 2014-11-26 | 2015-04-01 | 上海同仁药业有限公司 | Tilmicosin soluble powder and preparation method thereof |
| CN104721826A (en) * | 2015-04-14 | 2015-06-24 | 四川美嘉龙生物科技有限公司 | Tilmicosin preparation and preparation method thereof |
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2016
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670516A (en) * | 2012-05-29 | 2012-09-19 | 广东大华农动物保健品股份有限公司 | Tilmicosin soluble powder and preparation method thereof |
| CN104473876A (en) * | 2014-11-26 | 2015-04-01 | 上海同仁药业有限公司 | Tilmicosin soluble powder and preparation method thereof |
| CN104721826A (en) * | 2015-04-14 | 2015-06-24 | 四川美嘉龙生物科技有限公司 | Tilmicosin preparation and preparation method thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107853465A (en) * | 2017-11-06 | 2018-03-30 | 四川恒通动保生物科技有限公司 | A kind of pellet pre-mixing agent and preparation method thereof |
| CN110478321A (en) * | 2019-09-16 | 2019-11-22 | 四川恒通动物制药有限公司 | A kind of veterinary drug soluble powder that can be mixed thoroughly with pellet |
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