CN108853019A - Water-soluble Tilmicosin Florfenicol compound injection and preparation method and application - Google Patents

Water-soluble Tilmicosin Florfenicol compound injection and preparation method and application Download PDF

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Publication number
CN108853019A
CN108853019A CN201810982159.6A CN201810982159A CN108853019A CN 108853019 A CN108853019 A CN 108853019A CN 201810982159 A CN201810982159 A CN 201810982159A CN 108853019 A CN108853019 A CN 108853019A
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CN
China
Prior art keywords
tilmicosin
water
florfenicol
compound injection
soluble
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Pending
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CN201810982159.6A
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Chinese (zh)
Inventor
郑闳升
张友春
王丙云
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Foshan Tai Li Mei Biotechnology Co Ltd
Guangdong Sanshui Zhengda Animal Husbandry Development Co Ltd
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Foshan Tai Li Mei Biotechnology Co Ltd
Guangdong Sanshui Zhengda Animal Husbandry Development Co Ltd
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Priority to CN201810982159.6A priority Critical patent/CN108853019A/en
Publication of CN108853019A publication Critical patent/CN108853019A/en
Pending legal-status Critical Current

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/10Dispersions; Emulsions
    • A61K9/107Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/16Amides, e.g. hydroxamic acids
    • A61K31/165Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02Inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents

Abstract

The present invention provides a kind of water-soluble Tilmicosin Florfenicol compound injections, by mass percentage include following component:Tilmicosin, Florfenicol, Rou Dou guan isopropyl propionate, surfactant, cosurfactant, solvent, phosphoric acid and surplus water.Water-soluble Tilmicosin Florfenicol compound injection of the invention is water-soluble by force, bioavilability is high, stability is good, antibacterial activity is strong.

Description

Water-soluble Tilmicosin Florfenicol compound injection and preparation method and application
Technical field
The invention belongs to field of veterinary, in particular to a kind of water-soluble Tilmicosin Florfenicol compound injection and its system Preparation Method and application.
Background technique
Tilmicosin (Tilmicosin, TMS) is the dedicated antibiotic of livestock and poultry of tylosin synthesis, and it is new to belong to national three classes Veterinary drug.Tilmicosin is derivative of the tylosin after sour water solution, belongs to semi-synthetic macrolide antibiotics, molecule Formula is C46H80N2O13, molecular weight 869.15.Tilmicosin has antibacterial activity similar with Macrocyclolactone lactone kind medicine, blue to leather Family name's positive bacteria and some Gram-negative bacterias and mycoplasma are effective, especially to Actinobacillus pleuropneumoniae, pasteurella, golden yellow Color staphylococcus, streptococcus pyogenes, streptococcus pneumonia, corynebacterium pyogenes and livestock and poultry mycoplasma activity more than tylosin By force.With clinical common antibiotics without drug resistance of reporting to the leadship after accomplishing a task.Due to its special antibacterial activity and characteristics of pharmacokinetics, it is mainly used for treating The mazoitis of animal respiratory disease and lactating mammal.Tilmicosin is atomic to be dissolved in water, though phosphate is dissolved in water, exists steady It is qualitative it is poor, absorb after easily by the disadvantages such as gastric acid destroys, bioavilability is low.
Florfenicol (Florfenicol Powder) is amphenicols animal specific antibiotic, and molecular formula is C12H14CL2FNO4S, molecular weight 358.22.Florfenicol to a variety of Gram-positives, Gram-negative bacteria and mycoplasma etc. have compared with Strong antibacterial activity, haemolysis Pasteurella, to kill star Pasteurella, pig pleuropneumonia actinomyces highly sensitive to this product more, to chain Coccus, shigella dysenteriae, salmonella typhi, Klebsiella, Escherichia coli and resistance to ampicillin haemophilus influenzae are equal Sensitivity is clinically mainly used for bacterial infection bovine respiratory as caused by Pasteurella, haemophilus of ox, pig, chicken and fish Disease, actinomyces suis chest and abdomen pneumonia, fish dothienesis and mastadenitis of cow etc..But Florfenicol is not soluble in water, and utilization rate is low, must Large dosage (for oral administration reach of every 1kg weight need to need to reach 15~20mg to 20~30mg, injection) must be used, and needs every 24 hours weights Multiple administration, and large dosage of use has the shortcomings that the skin infections of newborn infants, immunosupress and anorexia.
To overcome disadvantage mentioned above, clinically Florfenicol and Tilmicosin are used in combination to be mutually reinforcing antibacterial effect, Dosage is reduced, shortens the course for the treatment of, reduce side effect, cardiac toxic, the pain etc. when especially reduction Tilmicosin is injected are answered Swash inhibitive ability of immunity, the skin infections of newborn infants etc. of reaction and Florfenicol.
Nano-emulsion (Nanoemulsion) is also referred to as micro emulsion (Microemlsion), and partial size is generally 1~100nm, is by oil The emulsion of a kind of stable transparent, low-viscosity that phase, water phase, surfactant and cosurfactant are formed by proper proportion.Only It wants the composition of four phases appropriate, homogeneous transparent can be formed or shows slightly the liquid of opalescence, be thermodynamic stable system.Nano-emulsion has Following advantages:Physical stability is good, can largely improve the dissolubility of the stability and insoluble drug of drug in water;Grain Diameter is small and uniform, and the dispersion degree of drug can be improved, and promotes the absorption of drug in vivo;The bioavilability of drug can be improved; Preparation process is easy, is easy to save.
Summary of the invention
It is an object of the invention to aiming at the above technical problems to be solved, provide a kind of water-soluble strong, biological utilisation The water-soluble Tilmicosin Florfenicol compound injection that degree is high, stability is good, antibacterial activity is strong.
It is a further object to provide the preparation sides of the water-soluble Tilmicosin Florfenicol compound injection Method.
A further object of the present invention is to provide the application of the water-soluble Tilmicosin Florfenicol compound injection.
In order to achieve the above object, the present invention provides following technical schemes:
A kind of water solubility Tilmicosin Florfenicol compound injection, includes following component by mass percentage:For rice It examines star 6%, Florfenicol 2%, Rou Dou guan isopropyl propionate (isopropyl myristate, IPM) 4.7%, surfactant 25.2%, help Surfactant 16.8%, solvent 1.6%, phosphatase 11 .5% and surplus water.
Water solubility Tilmicosin Florfenicol compound injection according to the present invention, wherein surfactant include but unlimited In tween, especially Tween 80.
Water solubility Tilmicosin Florfenicol compound injection according to the present invention, wherein cosurfactant include but not It is limited to dehydrated alcohol, 1,2- propylene glycol.
Water solubility Tilmicosin Florfenicol compound injection according to the present invention, wherein solvent includes but is not limited to formyl Amine solvent, especially dimethylformamide.
Water solubility Tilmicosin Florfenicol compound injection according to the present invention, wherein water is preferably injection distillation Water.
The present invention also provides the preparation methods of the water-soluble Tilmicosin Florfenicol compound injection comprising with Lower step:
Under the conditions of 25 DEG C, surfactant, cosurfactant and phosphoric acid are mixed, is then added while stirring and replaces rice Star is examined to make it completely dissolved.The florfenicol solution dissolved with solvent is added, is then mixed with Rou Dou guan isopropyl propionate It is even, water is added dropwise under vortex concussion, prepares nano-emulsion.
The present invention also provides the water-soluble Tilmicosin Florfenicol compound injection in preparation for treating animal Application in the drug of disease.
Preferably, the animal includes but is not limited to domestic animal, poultry, especially pig, ox.
A kind of water-soluble Tilmicosin Florfenicol compound injection provided by the invention is a kind of nano-emulsion preparation, is one Safe and efficient, the water-soluble strong nanometer Tilmicosin Florfenicol compound injection liquid formulation of kind.Said preparation, which has, absorbs fast, life Drug effective concentration in animal body and effective time can be improved in the features such as object availability is high, sustained release;In addition, the dosage is steady It is qualitative it is good, toxic side effect is small, antibacterial activity is strong, is suitble to the animals such as ruminant, pig, established base for clinical large-scale use Plinth.
The experimental results showed that water-soluble Tilmicosin Florfenicol compound injection of the invention can significantly reduce for rice The side effects such as the cardiac toxic of star and the skin infections of newborn infants of Florfenicol, inhibitive ability of immunity are examined, it is safer, convenient and efficient to use.
Detailed description of the invention
Fig. 1 shows the appearance of water-soluble Tilmicosin Florfenicol compound injection according to the present invention.
Fig. 2 is the type identification figure of water-soluble Tilmicosin Florfenicol compound injection according to the present invention.
Fig. 3 shows water-soluble Tilmicosin Florfenicol compound injection and distilled water mixing centrifuge results.
Fig. 4 shows water-soluble Tilmicosin Florfenicol compound injection long-time stability experimental result.
Specific embodiment
Combined with specific embodiments below, technical solution of the present invention is described in further detail, but the present invention is not limited to Following embodiment.
As unspecified, related reagent can be bought by commercial sources below.For simplicity, part operation The parameter, step and used instrument of operation are not described in detail, it should be understood that these are all well known to those skilled in the art and can Repetition.
Embodiment 1:The preparation of water-soluble Tilmicosin Florfenicol compound injection
According to the formula of following table 1, water-soluble Tilmicosin Florfenicol compound injection is prepared.
The formula table of the water-soluble Tilmicosin Florfenicol compound injection of table 1
Reagent Mass fraction % Density (20 DEG C) (g/ml)
Tilmicosin 6
Florfenicol 2
Rou Dou guan isopropyl propionate 4.7 0.850~0.860
Tween 80 (surfactant) 25.2 1.060~1.110
Dehydrated alcohol (cosurfactant) 11.2 0.789~0.791
1,2-PD (cosurfactant) 5.6 1.036~1.039
Dimethylformamide 1.6 0.94~
Phosphoric acid 1.5
Distilled water Surplus 1.000
Specific preparation process is as follows:
Under the conditions of 25 DEG C, Tween 80, dehydrated alcohol, 1,2-PD and phosphoric acid are mixed, are then added while stirring Tilmicosin makes it completely dissolved.The florfenicol solution dissolved with dimethylformamide is added, is stirred evenly, is added Rou Dou guan isopropyl propionate (IPM), which stirs evenly, is made oil phase liquid.Under vortex concussion, distilled water is added into oily phase dropwise, Prepare nano-emulsion.
It is observed that mixed surfactant (i.e. the synthesis of Tween 80, dehydrated alcohol and 1,2-PD) and Rou Dou guan acid Isopropyl ester (IPM) mass ratio can form homogeneous, transparent stable oily phase when being 9~10: 1, under whirlpool concussion, be slowly added to Distilled water forms the compound tilmicosin Florfenicol nanometer milk solution of light blue opalescence.
Water solubility Tilmicosin Florfenicol compound injection appearance clear, yellow made of the formula, viscosity compared with It is small, it is deeper that obvious color is compareed with blank newborn (not carrying Tilmicosin and Florfenicol), it may be possible to be equipped with Tilmicosin Reason, be specifically shown in Fig. 1.A is the control of blank cream in Fig. 1;B is water-soluble Tilmicosin Florfenicol compound injection.
The identification of water-soluble Tilmicosin Florfenicol compound injection type
The type of water-soluble Tilmicosin Florfenicol compound injection liquid formulation is identified using decoration method.
Decoration method is expanded in micro emulsion using oil-soluble dyes tonyred (red) and water-soluble dye serge blue (blue) Scattered speed judges the type of micro emulsion, if red diffusion is faster than blue is w/o type;It is on the contrary then be O/W type micro emulsion;The two one Sample is fast, then is bicontinuous.
Water solubility Tilmicosin Florfenicol compound injection made of embodiment 1 is made an addition in two test tubes of A, B, point Not Di Jia methylene blue (A) and tonyred (B), just add dyestuff the case where as shown in left figure I in Fig. 2, after 2h, it is seen that addition dye Spread condition after expecting 2h, as shown in right figure II in Fig. 2, diffusion velocity of the methylene blue in injection is significantly faster than that the Sudan It is red, it is possible to determine that nanometer Tilmicosin Florfenicol compound injection is O/W type nano-emulsion.
The stability of water-soluble Tilmicosin Florfenicol compound injection
Appearance:The appearance of nano-emulsion is visually observed, if clear, shows to have good stability;If it is muddy, cotton-shaped heavy to occur It forms sediment or is layered, then show unstable.As a result layering is had no, it is in stable condition still to be clear and bright, as shown in Figure 3.
Accelerated stability test:The water-soluble Tilmicosin Florfenicol compound injection liquid formulation and distilled water that will be prepared With 10:0,9:1,8:2,5:5,2:8,1:It is centrifuged after 9 volume ratio mixing, sets centrifuge, 10000r/min is centrifuged under room temperature 10min, whether there is or not layering or Precipitations for observation solution.
Long-term stable experiment:The water-soluble Tilmicosin Florfenicol compound injection of preparation is placed 6 under room temperature It a month, samples weekly, visually observing injection, whether there is or not layering or Precipitations.As shown in figure 4, by water-soluble Tilmicosin fluorobenzene Buddhist nun examines after compound injection stores 6 months at room temperature, in stable condition, keeps clear not stratified.
The bacteriostatic activity of water-soluble Tilmicosin Florfenicol compound injection
Using micro broth dilution method, test organisms is Actinobacillus, and concrete operations are as follows:
10 times diluted according to embodiments of the present invention 1 of Tilmicosin Florfenicol compound is added in the sterile column of 96 orifice plate the 1st Injection, the 2nd~11 column are respectively plus 20,40,80,160,320,640,1280,2560,5120,10240 times diluted are examined for rice Star Florfenicol compound injection, every 10 μ l of hole, the 12nd column are not added drug and make growth control.By 0.5 Maxwell putting than turbid standard Line bar bacteria suspension, after MH meat soup (caseinhydrolysate culture medium) is by the dilution of 1: 1000 volume ratio, to every 90 μ l of Kong Zhongjia, sealing In 35 DEG C of normal air incubators of postposition, it is incubated for judging result after 16~20h.
As a result judge, be MIC (minimal inhibitory concentration) to completely inhibit the lowest concentration of drug of bacterial growth in aperture. When the interior obvious growth test of bacterium of Positive control wells (being free of antibiotic) is just significant.It is single when occurring in micro broth dilution method When one jump hole, the highest drug concentration for inhibiting bacterial growth should be recorded.Such as there are many places and jump hole, then should not report as a result, needing It repeats to test.
Bacteriostatic activity test result shows that the MIC of Tilmicosin Florfenicol compound injection is 1.17mg/L+ 0.39mg/L, water-soluble Tilmicosin Florfenicol compound injection of the invention make Actinobacillus with stronger inhibition With.
The clinical use dosage of water-soluble Tilmicosin Florfenicol compound injection
After water-soluble Tilmicosin Florfenicol compound injection intramuscular injection of the invention, directly with nano-emulsion particle quilt Blood absorption, then by it is some become inflammatory phagocyte phagocytosis after take inflammatory loci to, make the medicine of inflammatory loci (such as alveolar tissue) Object concentration is much higher than blood concentration, thus plays certain targeting anti-inflammatory effect, improves sterilization antiphlogistic effects.In addition, big Drag residence is measured in inflammatory loci, is just substantially reduced by the speed of liver metabolism, thus extends the half-life period of drug, test is aobvious Show that the 48 hours repeat administrations in interval can steadily maintain effective dose.The clinical treatment dosage that test obtains is for every kg body Weight, 5~7.5mg of ox, pig 3~5mg energy perfection reach therapeutic effect, this is greatly lowered drug dosage.
The clinical safety of water-soluble Tilmicosin Florfenicol compound injection
Traditional Tilmicosin injection has cardiac toxic to many animals, and novel chiral synthon allusion quotation only lists the application method of ox, And water-soluble Tilmicosin Florfenicol compound injection of the invention subtracts the dosage of drug significantly because of technique and synergistic effect It is few, thus some side effects are avoided, improve safety.In clinical treatment experiment, pig 3~5mg of every 1kg weight, ox 5~ 7.5mg can reach ideal treatment, and safety, still pacify when every 36~48 hours duplicate injection one-time continuous are with 3 times Entirely.Still be resistant to when pig therapeutic dose is increased to every 1kg weight 10mg, but to some pigs of being critically ill, weak constitution pig exist than Biggish risk, the death rate (dead in 1 hour after injection) about 0.5~1.0% of this dosage of experiment statistics;When more than every The death rate obviously rises when the dosage of 1kg weight 12.5mg, increased risk, the death rate when dosage reaches every 1kg weight 15mg It can reach 25%, thus be forbidden to use this dosage.
Therefore, the present invention is recommended to use method and dosage is:Domestic animal intramuscular injection, every kg weight, 0.05~0.1ml of pig (3 ~6mg), 0.1~0.15ml of ox (6~9mg) is spaced duplicate injection in 36~48 hours, is used in conjunction 2~3 times.Forbid excess and it is long when Between use.
Water-soluble Tilmicosin Florfenicol compound injection of the invention has clinically done many therapeutic tests, test Proof such as coughs, breathes to pig bacterial respiratory tract disease or mixed infection class disease, having a fever and clinical symptoms are unconspicuous Subclinical case has certain therapeutic effect.In practical applications, several aspects under mainly having:
(1) in terms of porcine respiratory disease, this product antibacterial action is fast and lasting, is inhibiting inflammatory exudation and is promoting inflammatory Material absorbing etc. has wide application, and thorough treatment has special effect to intractable case and critical case, be Bronchopneumonia, The respiratory diseases such as contagious pleuropneumonia, disease of breathing, lung epidemic disease, Haemophilus parasuis and systemic mixed infection class disease It is preferred;
(2) it can be effectively controlled secondary infection for viral diseases such as pig annulus indigo plant ears, significantly reduce mortality, mention High curative rate;
(3) in terms of sows in perinatal period health care, anorexia, constipation, movement reduction, spirit are shown not to sow antenatal postpartum Peace, production inability, micromazia, lactation reduction, mammitis, hysteritis etc. have treatment and prevention effect, and have one Fixed crosses milk health-care effect;
(4) in the respiratory disease for treating pig and ox, dosage can be reduced compared with conventional formulation, and can be spaced Duplicate injection 2~3 times after 48 hours, are more advantageous to radical cure in this way.

Claims (9)

1. a kind of water solubility Tilmicosin Florfenicol compound injection, it is characterised in that include by mass percentage below at Point:Tilmicosin 6%, Florfenicol 2%, Rou Dou guan isopropyl propionate 4.7%, surfactant 25.2%, cosurfactant 16.8%, the water of solvent 1.6%, phosphatase 11 .5% and surplus.
2. water solubility Tilmicosin Florfenicol compound injection according to claim 1, which is characterized in that the surface Activating agent is tween.
3. water solubility Tilmicosin Florfenicol compound injection according to claim 1, which is characterized in that the surface Activating agent is Tween 80.
4. water solubility Tilmicosin Florfenicol compound injection according to claim 1, which is characterized in that described to help table Face activating agent is any one of dehydrated alcohol, 1,2- propylene glycol or two kinds.
5. water solubility Tilmicosin Florfenicol compound injection according to claim 1, which is characterized in that the solvent It is dimethylformamide.
6. water solubility Tilmicosin Florfenicol compound injection according to claim 1, which is characterized in that the water is Distilled water for injection.
7. the preparation method of water solubility Tilmicosin Florfenicol compound injection as claimed in any one of claims 1 to 6, packet Include following steps:
Under the conditions of 25 DEG C, surfactant, cosurfactant and phosphoric acid are mixed, Tilmicosin is then added while stirring It makes it completely dissolved, adds the florfenicol solution dissolved with solvent, be then uniformly mixed with Rou Dou guan isopropyl propionate, Water is added dropwise under vortex concussion, prepares nano-emulsion.
8. water solubility Tilmicosin Florfenicol compound injection as claimed in any one of claims 1 to 6 is in preparation for treating Application in the drug of Animal diseases.
9. application according to claim 8, which is characterized in that the animal is livestock or poultry.
CN201810982159.6A 2018-08-27 2018-08-27 Water-soluble Tilmicosin Florfenicol compound injection and preparation method and application Pending CN108853019A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112005980A (en) * 2020-09-11 2020-12-01 佛山泰立美生物科技有限公司 Carnivorous fish bait and preparation method and use method thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000513011A (en) * 1997-03-20 2000-10-03 ファルマシア・アンド・アップジョン・カンパニー Administration of antibiotics for injection to the ears of animals
CN101983632A (en) * 2010-10-11 2011-03-09 西北农林科技大学 Compound Tilmicosin nanoemulsion antibacterial agent and preparation method thereof
CN104161768A (en) * 2013-08-30 2014-11-26 郑州后羿制药有限公司 Veterinary compound tilmicosin injection and preparation method thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000513011A (en) * 1997-03-20 2000-10-03 ファルマシア・アンド・アップジョン・カンパニー Administration of antibiotics for injection to the ears of animals
CN101983632A (en) * 2010-10-11 2011-03-09 西北农林科技大学 Compound Tilmicosin nanoemulsion antibacterial agent and preparation method thereof
CN104161768A (en) * 2013-08-30 2014-11-26 郑州后羿制药有限公司 Veterinary compound tilmicosin injection and preparation method thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112005980A (en) * 2020-09-11 2020-12-01 佛山泰立美生物科技有限公司 Carnivorous fish bait and preparation method and use method thereof

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Application publication date: 20181123