CN104546704B - A kind of milk cow dry breast phase Ceftiofur Hydrochloride breast injection and preparation method thereof - Google Patents
A kind of milk cow dry breast phase Ceftiofur Hydrochloride breast injection and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a kind of Ceftiofur Hydrochloride breast injection（Dry breast phase）And preparation method thereof.The Ceftiofur Hydrochloride breast injection, is made up of following supplementary materials：2.5 10g of Ceftiofur Hydrochloride, 0.5 5g of glycerin monostearate, 0.5 5g of suspending agent, vegetable oil add to 100ml.Its preparation technology is as follows：After appropriate vegetable oil and glycerin monostearate mixing, then heating fusing is added thereto to suspending agent, Ceftiofur Hydrochloride, then plus vegetable oil to full dose, grinding is uniform, and Ceftiofur Hydrochloride breast injection is obtained.The breast injection has the advantage that：Insoluble drug release is slow, and bioavilability is high, little to local tissue stimulation；Every ox each newborn area's independent medication, it is to avoid cross-infection；Injected by breast, it is easy to use, it is to avoid the animal stress reaction that drug administration by injection causes, provide facility for clinical application；It is evident in efficacy, with high promotional value.
Description
Technical field
The present invention relates to a kind of Ceftiofur Hydrochloride breast injection（Dry breast phase）And preparation method thereof.
Background technology
Ceftiofur (Ceftiofur, CEF) is the third generation cephalo antibiotics of animal specific.The antibacterial of Ceftiofur
Spectrum is wide, antibacterial activity is strong, has extremely strong antibacterial activity to gram-positive bacteria, Gram-negative bacteria and some anaerobic bacterias；
And with stable beta-lactam nucleus, for the various bacteriums that can produce beta-lactamase also have good killing effect, be difficult
Antibody-resistant bacterium and cross resistance are produced, is clinically mainly used in the sensitive microbial various infection of many animals.Therefore, apply
Ceftiofur treatment livestock and poultry is significant.
Now the Ceftiofur formulation of research has injection Ceftiofur sodium injection, Ceftiofur sodium lipidosome etc. both at home and abroad
Formulation, the shortcoming of these formulations is that action time is short, and its administrated method is substantially injection daily and once, is used in conjunction 3～5 days.Cause
This, a kind of insoluble drug release of exploitation is slow, bioavilability is high and ceftiofur formulation that is using suitable for milk cow dry breast phase has
Important realistic meaning.
The content of the invention
It is an object of the invention to provide a kind of Ceftiofur Hydrochloride breast injection（Dry breast phase）And preparation method thereof.
Ceftiofur Hydrochloride breast injection provided by the present invention（Dry breast phase）, it is made up of following supplementary materials：Hydrochloric acid head
Spore thiophene furan（Bulk drug）2.5-10g, glycerin monostearate 0.5-5g, suspending agent 0.5-5g, vegetable oil add to 100ml.
The Ceftiofur Hydrochloride breast injection further can be made up of following supplementary materials：Ceftiofur Hydrochloride（Raw material
Medicine）5g, glycerin monostearate 0.5-5g, suspending agent 0.5-5g, vegetable oil add to 100ml.
Wherein, the vegetable oil specifically may be selected from following at least one：Soybean oil, tea oil, corn oil, peanut oil and cottonseed
Oil.The vegetable oil can be further soybean oil.
The suspending agent specifically may be selected from following at least one：Tween 80, sorbester p17 and soybean lecithin.The suspending agent enters
One step can be sorbester p17.
The particle diameter of the Ceftiofur Hydrochloride bulk drug can be 5-10 μm.
Oil suspension of the proterties of Ceftiofur Hydrochloride breast injection of the present invention for off-white color to yellow.
The preparation method of above-mentioned Ceftiofur Hydrochloride breast injection, by vegetable oil, glycerin monostearate and suspending agent
Macromolecular compound dicyandiamide solution is made, then the aseptic micro mist of Ceftiofur Hydrochloride is added, continued agitation grinding and make hydrochloric acid
Ceftiofur breast injection.
Concrete preparation method comprises the steps：
1）After appropriate vegetable oil and glycerin monostearate mixing, heating fusing obtains mixed system（That is producing high-molecular
Compound dicyandiamide solution）；
2）Add suspending agent, Ceftiofur Hydrochloride in the mixed system, then plus vegetable oil to full dose, grinding is uniform,
Obtain final product the Ceftiofur Hydrochloride breast injection（Dry breast phase）.
Wherein, step 1）Described in the condition that heats be：60～80 DEG C heat 15～30 minutes.Step 1 under normal circumstances）
Used in vegetable oil consumption for vegetable oil total amount 40%-60%.
Step 2）Described in grind and can carry out in colloid mill.
The vegetable oil is using the front pretreatment also needed through filtration and heat sterilization.The condition of the heat sterilization
For：150-160 DEG C of sterilizing 2-3 hour.
Ceftiofur Hydrochloride breast injection provided by the present invention（Dry breast phase）Milk cow dry breast phase mammitis is had aobvious
Write curative effect.
Compared with prior art, the present invention has the advantages that：
（1）Convenient drug administration is quick, reduces substantial amounts of manpower and materials；
（2）Animal stress reaction is little, reduces the damage of animal body；
（3）Simple production process, the preparation for obtaining is uniform, dispersiveness, good stability, it is easy to extension production；
（4）Every ox each newborn area's independent medication, i.e., independently use medicine equipment（Preparation）, it is to avoid cross-infection；
（5）, for parenteral solution, insoluble drug release is slow for this preparation, and bioavilability is high, to local tissue stimulation
Property it is low, clinical efficacy significantly, with high promotional value.
Specific embodiment
With reference to specific embodiment, the present invention is further illustrated, but the invention is not limited in this.
Experimental technique described in following embodiments, if no special instructions, is conventional method；The reagent and material, such as
Without specified otherwise, can be obtained by commercial sources.
The Ceftiofur Hydrochloride breast injection that the present invention is provided is a kind of preparation being evenly distributed, concrete preparation method bag
Include following steps：
A. by vegetable oil（Such as neutral soybean oil）Jing is filtered and is let cool after heat sterilization；
B. appropriate pretreated vegetable oil is taken, the glycerin monostearate of 0.5～5g is added；
C.60～80 DEG C heat 15～30 minutes, treat glycerin monostearate melt, after stirring, be cooled to 40 DEG C it is left
The right side, adds the suspending agent of 0.5～5g（Such as sorbester p17）, 2.5～10g Ceftiofur Hydrochloride（5-10 μm of particle diameter）, then add plant
Thing oil to total amount is 100ml；
D. grind uniform, Ceftiofur Hydrochloride breast injection is obtained；
E. medicine is loaded and is injected in pipe, sealed, sterilizing, lamp inspection, packaging.
In following embodiments to the detection method of the sedimentation granularity of breast injection it is：Apparatus plug graduated cylinder takes test sample
50ml, close plug firmly shake 1 minute, write down the beginning height H0 of suspension, stand 3 hours, write down the final height of suspended matter
H, is calculated as follows, as a result as follows：Sedimentation specific volume F=H/H0, is not less than 0.90 i.e. qualified.
The method of steriling test is：Take this product 10, every 10ml（With front shaking up）, after mixing, 25ml is taken, is added aseptic
1% Tween-80 and 0.1% peptone solution 250ml, shake well make dispersion, add penicillase solution（Per 1mg hydrochloric acid cephalos
Thiophene furan adds about 14400 unit of penicillase）, shake well 30 minutes, mixing take mixed liquor 10ml, are separately added into 100ml sulphur second
In alcohol hydrochlorate broth and improvement Martin's culture medium, shaking table culture 14 days under corresponding conditionses take nutrient solution and are inoculated in tiltedly
On the culture medium of face, Bacteria Culture 2 days, fungal culture 3 days are checked in accordance with the law（Annex page 137）, as a result should meet regulation.
Embodiment 1, prepare Ceftiofur Hydrochloride breast injection（Dry breast phase）
Preparation method is as follows：
1）Ceftiofur Hydrochloride aseptic powder Jing ultramicro grinding is obtained into the aseptic micro mist of 5-10 μm of Ceftiofur Hydrochloride of particle diameter；
2）Soybean oil Jing is filtered and heat sterilization（160 DEG C sterilize 2 hours）Afterwards, put standby at room temperature；
3）Take appropriate pretreated soybean oil（For the 40%-60% of the total consumption of soybean oil）, add glycerin monostearate；
Heat and stir（60 DEG C heat 15 minutes）, treat that glycerin monostearate melts, after stirring, be cooled to 40 DEG C, add
Sorbester p17, Ceftiofur Hydrochloride, then soya-bean oil is increased to full dose；
4）Grind uniform in aseptic colloid mill, Ceftiofur Hydrochloride breast injection is obtained.
Gained Ceftiofur Hydrochloride breast injection（Dry breast phase）Proterties for off-white color to yellow oil suspension.
The said goods are carried out settling granularity and Sterility testing, which meets the quality standard of breast injection.
Embodiment 2, prepare Ceftiofur Hydrochloride breast injection（Dry breast phase）
Preparation method is as follows：
1）Ceftiofur Hydrochloride aseptic powder Jing ultramicro grinding is obtained into the aseptic micro mist of 5-10 μm of Ceftiofur Hydrochloride of particle diameter；
2）Soybean oil Jing is filtered and heat sterilization（150 DEG C sterilize 3 hours）Afterwards, put standby at room temperature；
3）Take appropriate pretreated soybean oil（For the 40%-60% of the total consumption of soybean oil）, add glycerin monostearate；
Heat and stir（80 DEG C heat 30 minutes）, treat that glycerin monostearate melts, after stirring, be cooled to 40 DEG C, add
Sorbester p17, Ceftiofur Hydrochloride, then soya-bean oil is increased to full dose；
4）Grind uniform in aseptic colloid mill, Ceftiofur Hydrochloride breast injection is obtained.
Gained Ceftiofur Hydrochloride breast injection（Dry breast phase）Proterties for off-white color to yellow oil suspension.
The said goods are carried out settling granularity and Sterility testing, which meets the quality standard of breast injection.
Embodiment 3, prepare Ceftiofur Hydrochloride breast injection
Preparation method is with embodiment 2.
Oil suspension of the proterties of gained Ceftiofur Hydrochloride breast injection for off-white color to yellow.
The said goods are carried out settling granularity and Sterility testing, which meets the quality standard of breast injection.
Embodiment 4, prepare Ceftiofur Hydrochloride breast injection
Preparation method is with embodiment 2.
Oil suspension of the proterties of gained Ceftiofur Hydrochloride breast injection for off-white color to yellow.
The said goods are carried out settling granularity and Sterility testing, which meets the quality standard of breast injection.
Embodiment 5, prepare Ceftiofur Hydrochloride breast injection
Preparation method is with embodiment 2.
Oil suspension of the proterties of gained Ceftiofur Hydrochloride breast injection for off-white color to yellow.
The said goods are carried out settling granularity and Sterility testing, which meets the quality standard of breast injection.
Embodiment 6, prepare Ceftiofur Hydrochloride breast injection
Preparation method is with embodiment 2.
Oil suspension of the proterties of gained Ceftiofur Hydrochloride breast injection for off-white color to yellow.
The said goods are carried out settling granularity and Sterility testing, which meets the quality standard of breast injection.
Embodiment 7, Ceftiofur Hydrochloride breast injection（Dry breast phase）The vivo efficacy of milk cow is tested
1）Ceftiofur Hydrochloride breast injection（Dry breast phase）Safety testing to milk cow
Test is random each 6 from healthy milk cow in lactation period primiparity and Jing products, and single gives embodiment 2 respectively in four Ge Ru areas
The Ceftiofur Hydrochloride breast injection of preparation（Dry breast phase）1（Specification：500mg；10ml）.
1 day and 0 day before administration（Before administration）Collection milk sample is each 1 time；12 hours, 3 days, 5 days, 7 days and 10 days after administration
Milk sample 1 time is adopted respectively, sampling Shi Sigeru areas are required to sampling, and discard first three milk.
Data Collection：Continuous Observation, record milk cow mark, observing time, examination are carried out to milk cow is administered during whole test
Test date and time, every parameter such as cow head daily yielding and body temperature.Somatic number in the gathered milk sample detection breast of each time point
（SCC）, the clinical symptoms such as milk cow red and swollen heat pain are observed by palpation.
Bacteria distribution：Respectively each collection milk sample on the 10th 1 time after 0 day and administration before administration（20mL）Carry out bacteriology inspection
Look into.First breast is rinsed with clear water during sampling, nipple and surrounding are carried out disinfection with 0.1% bromogeramine or 75% ethanol, treat wine
After essence volatilization, manual milking, after discarding first three milk, gathers milk sample in sterilizing test tubes with sterilizing test tubes, posts label, low temperature
（4℃）Preserve and laboratory separation detection is sent in 6h.
Pathogen is separated with multiple choices medium culture.Each milk sample is seeded to into selective medium and separates various diseases
Opportunistic pathogen.After the purified culture of isolated strains, its species is identified according to colonial morphology, dyeing characteristic, Biochemical Characteristics.It is main to separate gold
Staphylococcus aureus, streptococcus (streptococcus dysgalactiae, streptococcus uberis), Escherichia coli.
As a result show, during whole test, give without significant change compared with before administration after somatic number is administered in cow's milk
After medicine, bacteria distribution number is reduced, and milk production of cow has no significant changes, and the clinical conditions such as red, swollen, hot, pain does not occur in the newborn area of administration
Shape.Show based on the above results, milk cow gives Ceftiofur Hydrochloride breast injection according to recommended dose single（Dry breast phase）, it is right
Milk cow has higher security without any bad reaction, said preparation.
2）Ceftiofur Hydrochloride breast injection（Dry breast phase）In the residue test of cow's milk
Choose 10 health and will enter dry cow, milked before into dry breast phase for the last time after finishing, per head
Each newborn area of ox gives the Ceftiofur Hydrochloride breast injection of the preparation of embodiment 2（Dry breast phase）1（Specification：500mg；
10ml）.Furan is removed in 12h, 24h, 36h, 48h, 60h, 72h collection composite sample after milk cow calving and with the milk set up
Mutter formoxyl Ceftiofur acetamide（DCA, Ceftiofur and its metabolin derivatization product）Ultra Performance Liquid Chromatography series connection
Triple level Four bar mass spectrographies（UPLC-MS/MS）The concentration of DCA in detection milk.Concrete detection method：Weigh 1mL milk in
In 10mL centrifuge tube with cover；3mL acetonitriles are added, after whirling motion 1min, 10000r/min, 4 DEG C of centrifugation 10min；Take supernatant in
In 50ml polypropylene centrifuge tubes, remaining 1mL or so is concentrated into Nitrogen evaporator under 40 DEG C of water-baths；Addition 5mL DTE extracts, 50
DEG C water-bath is vibrated 20 minutes, is subsequently added 2mL iodoacetamide extracts, and after being sufficiently mixed, lucifuge stands 30 minutes, is then injected into
HLB solid phase extraction columns（The advance Jing 3mL methyl alcohol activation of HLB, 3mL water balances）, then extracted with 3mL5% methyl alcohol water washings HLB solid phase
Pillar is taken, is finally eluted with 3mL acetonitriles, collection eluent is in 10mL teat glasses.Eluent nitrogen under 40 DEG C of water-baths blows dense
It is reduced to dry, residue -0.1% aqueous formic acid of 1mL acetonitriles（5:95, V/V）Redissolve, whirling motion 1min makes residue on centrifugation tube wall
After all dissolving, 0.22 μm of filter membrane is crossed in sample introduction bottle, detected with UPLC-MS/MS liquid matter instrument.
The de- furanylcarbonyl cephalo thiophene of acetyl is turned to by Ceftiofur Hydrochloride and its metabolin derivative in residue detection test
Furan acetamide（DCA）, establish the Ultra Performance Liquid Chromatography tandem mass spectrum of DCA in milk（UPLC-MS/MS）Assay method.It is logical
Crossing acetonitrile extraction, derivatization, SPE, nitrogen and the step such as drying up, redissolve carries out sample pre-treatments, then uses UPLC-MS/MS
Determine the concentration of DCA in milk.The calibration curve coefficient correlation that this method is set up（r）For 0.9991.Select three concentration levels
Recovery test is added, between 82.52%-105.86%, variation within batch coefficient is 2.95%～9.82% to the rate of recovery, batch anaplasia
Different coefficient is 6.41%～7.43%.Detections of the DCA in milk is limited to 0.05 μ g/L, is quantitatively limited to 0.1 μ g/L.
As a result show：Ceftiofur Hydrochloride breast injection（Dry breast phase）It is administered by recommended dose, after dry breast phase terminates, ox
Ceftiofur residual marker-remove furoyl Ceftiofur DFC is can't detect in breast, less than European Union and China's States Pharmacopoeia specifications
In milk, the MRL of Ceftiofur is 100 μ g/kg.Therefore Ceftiofur Hydrochloride breast injection（Dry breast phase）For
Dry milk phase mastitis for milk cows prevents and the off-drug period for the treatment of is zero day.
3）Ceftiofur Hydrochloride breast injection（Dry breast phase）Pharmacodynamics test to mastitis for milk cows
The milk cow that dry breast phase is closed on from 6000 Fresians of 4 test cattle farms selects 60, is randomly divided into 5
Group, 12 per group.It is divided into 3 test medicine groups（I, II, III group）, height is given respectively（2）, in（1）, it is low（1/2）Agent
The Ceftiofur Hydrochloride breast injection (dry breast phase) of amount；1 drug control group（IV groups）, give benzathine cloxacillin injection
Liquid 1；1 non-administration blank control group（V groups）.Above-mentioned Ceftiofur Hydrochloride breast injection is sample prepared by embodiment 2,
Specification is 500mg；10ml.
Test milk cow is milked after finishing before into dry breast phase for the last time, four Ge Ru areas sterilization nipple perfusion administration, gives
After medicine, massaging breasts are distributed medicaments uniformity.The clinical condition and breast condition of observed and recorded medication milk cow；Respectively in dry breast phase
When front last time is milked with being milked after calving for the first time, aseptic collection milk sample carries out bacteriology checking；Count each test group milk
There is pathogenic bacteria detection before ox administration in milk sample and after calving, do not detect newborn area's number and milk cow number of pathogenic bacteria（It is shown in Table 1）, calculate each
Group mastitis for milk cows treatment of infection and the success rate of prevention；Detect without pathogenic bacteria in milk sample before counting the administration of each test group milk cow and
Newborn area's number and milk cow number of pathogenic bacteria are detected after calving（It is shown in Table 2）, calculate the new infection rate of each test group milk cow pathogen.It is comprehensive
Evaluate treatment and preventive effect of the medicine to dry cow breast infection.
Compare with calving rear udder attachment infection rate before the test milk cow medication of table 1
Note：1）Detection infectious bacteria milk cow number/detection milk cow number, newborn area's infection rate=detection infectious bacteria in head infection rate=breast
Newborn area's number/detection breast area number
The test milk cow of table 2 calving breast infection on the 5th is removed and new infections situation
Note：1）Head clearance rate=（Detection infectious bacteria milk in detection infectious bacteria milk cow number-calving rear udder attachment in medication fore udder
Ox number）Detection infectious bacteria milk cow number in/medication fore udder；2）Newborn area's clearance rate=（Infectious bacteria breast area number-calving is detected before medication
Infectious bacteria breast area number is detected afterwards）Infectious bacteria breast area number is detected before/medication；3）New infeetioa ox be medication before do not detect breast infection bacterium
And after calving, detect breast infection bacterium；4）New infeetioa breast area detects infectious bacteria not detect infectious bacteria before medication after calving；5）
Between same column numerical value, compared with blank control group, tool * * subscripts represent difference extremely significantly (P<0.01).
Result of the test shows：
1）Ceftiofur Hydrochloride breast injection（Dry breast phase）Pathogenic bacteria in dry cow breast are had good clear
Except effect.Wherein high, middle dosage reaches 83.3%-85.7% to the head clearance rate of infectious bacteria in cow breast, and newborn area's clearance rate reaches
93.3%-95.0%, high, the Ceftiofur Hydrochloride breast injection of middle dosage（Dry breast phase）Action effect without significant difference（P ＞
0.05）, (head clearance rate 42.9%, newborn area's clearance rate is 50.0%) to be superior to control drug benzathine cloxacillin parenteral solution；Low dose
Amount group to the head clearance rate of pathogenic bacteria in cow breast also up to 50.0%, newborn area's clearance rate up to 61.5%, action effect with it is right
It is suitable according to medicine.
2）Dry cow irrigates Ceftiofur Hydrochloride breast injection（Dry breast phase）With benzathine cloxacillin parenteral solution
Control drug can significantly reduce the infection rate of various pathogenic bacteria in cow breast.With the prevention of benzathine cloxacillin parenteral solution
Compared with therapeutic effect, high, the Ceftiofur Hydrochloride breast injection of middle dosage（Dry breast phase）To dry cow head infection rate
It is more notable with the improvement result of newborn area's infection rate；Head sense of the low dosage Ceftiofur Hydrochloride breast injection to dry breast phase mammitis
The improvement of Ran Shuaiheru areas infection rate is suitable with control drug；The scorching head infection rate of blank control group milk cow dry breast phase rear udder attachment and
Newborn area's infection slightly rises.
3）Dry cow uses Ceftiofur Hydrochloride breast injection（Dry breast phase）Can obviously reduce various thin in breast
The new infections rate of bacterium.Dry cow irrigates Ceftiofur Hydrochloride breast injection（Dry breast phase）With control drug benzyl star neighbour's chlorine
Penicillin injection liquid is respectively provided with the effect that scavenging action and prevention postpartum suffer from mammitis to various pathogenic bacteria in cow breast.Wherein
High, the Ceftiofur Hydrochloride breast injection of middle dosage（Dry breast phase）To streptococcus uberis, streptococcus dysgalactiae, S. aureus L-forms in breast
And colibacillary scavenging action and prevention postpartum suffer from mammitis action effect it is preferable；The hydrochloric acid head of control drug and low dosage
Spore thiophene furan breast injection（Dry breast phase）Scavenging action and prevention postpartum to mammitis pathogenic bacteria is suffered from mammitis and also has a constant current modulation
Effect.
4）Milk cow dry breast phase irrigates Ceftiofur Hydrochloride breast injection（Dry breast phase）, to mammitis pathogenic bacteria streptococcus,
S. aureus L-forms, Escherichia coli etc. has well control scavenging action.It is high（2）, in（1）The Ceftiofur Hydrochloride breast injection of dosage
（Dry breast phase）To the treatment of pathogenic bacteria in dry cow breast, there was no significant difference with preventive effect, it is therefore proposed that Clinical practice
Ceftiofur Hydrochloride breast injection（Dry breast phase）Treat and prevent mastitis for milk cows dosage be：When milk cow enters the dry milk phase,
Each newborn area gives 1 Ceftiofur Hydrochloride breast injection（Dry breast phase）（Specification：500mg；10ml）.
The method that vivo efficacy according to embodiment 7 is tested carries out identical test to the product of embodiment 1,3-6, its knot
Fruit is suitable with the effect of embodiment 2.The Ceftiofur Hydrochloride breast injection of present invention offer is provided（Dry breast phase）Safely, without residual
Stay, it is little to local tissue stimulation, evident in efficacy, with high promotional value.
Claims (4)
1. a kind of Ceftiofur Hydrochloride breast injection, is made up of following supplementary materials：Ceftiofur Hydrochloride 5g, monostearate are sweet
Grease 0.5-5g, suspending agent 0.5-5 g, vegetable oil add to 100ml；
The vegetable oil is soybean oil；The suspending agent is sorbester p17；
The particle diameter of the Ceftiofur Hydrochloride is 5-10 μm；
The Ceftiofur Hydrochloride breast injection is used for the prevention and/or treatment of milk cow dry breast phase mammitis；
The Ceftiofur Hydrochloride breast injection is prepared according to the method for comprising the steps：
1）After the appropriate vegetable oil and glycerin monostearate mixing, heating fusing obtains mixed system；
2）Add the suspending agent, the Ceftiofur Hydrochloride in the mixed system, then plus vegetable oil to full dose, grinding is equal
It is even, obtain final product the Ceftiofur Hydrochloride breast injection.
2. Ceftiofur Hydrochloride breast injection according to claim 1, it is characterised in that：Step 1）Described in heat
Condition is：60 ~ 80 DEG C heat 15 ~ 30 minutes；Step 2）Described in grind and carry out in colloid mill；Step 1）Described in vegetable oil
Consumption for vegetable oil total amount 40%-60%.
3. Ceftiofur Hydrochloride breast injection according to claim 1 and 2, it is characterised in that：The vegetable oil makes
With the front pretreatment also needed through filtration and heat sterilization；The condition of the heat sterilization is：150-160 DEG C of sterilizing 2-3 is little
When.
4. the Ceftiofur Hydrochloride breast injection any one of claim 1-3 is preparing prevention and/or is treating milk cow
Application in dry breast phase mammitis medicine.
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| CN105726461B (en) * | 2014-12-10 | 2021-02-09 | 瑞普（天津）生物药业有限公司 | Ceftiofur hydrochloride breast injection in dry period |
| CN109394679B (en) * | 2018-12-07 | 2020-06-09 | 中国农业科学院饲料研究所 | Rifaximin ointment for animal hoof diseases |
| CN110063991B (en) * | 2019-05-19 | 2022-04-26 | 浙江海正动物保健品有限公司 | Compound ceftiofur hydrochloride breast injection |
| CN112924633B (en) * | 2021-05-10 | 2021-08-10 | 天津瑞普生物技术股份有限公司 | Sterility detection method for ceftiofur oil suspension injection |
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| CN101721366A (en) * | 2010-01-13 | 2010-06-09 | 洛阳惠中兽药有限公司 | Components and preparation method of beta-lactam injection |
| CN102488694A (en) * | 2011-12-21 | 2012-06-13 | 齐鲁动物保健品有限公司 | Perfusion medicament for treating milk cow mastitis and preparation method thereof |
| CN103006672A (en) * | 2012-12-26 | 2013-04-03 | 齐鲁动物保健品有限公司 | Vitamin-D3-contained filling agent for preventing dairy cow mastitis and preparation method of filling agent |
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