CN104546703B - A kind of Lactation of Dairy Cow phase is with Cefquinome sulfate breast injection and preparation method thereof - Google Patents
A kind of Lactation of Dairy Cow phase is with Cefquinome sulfate breast injection and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a kind of Cefquinome sulfate breast injection（Lactation period）And preparation method thereof.The Cefquinome sulfate breast injection is made up of following supplementary materials：The 0.15g of Cefquinome sulfate 0.05（In terms of Cefquinome）, the 0.08g of glycerin monostearate 0.008, the 0.08g of suspending agent 0.008, vegetable oil add to 8.0g.Preparation technology is as follows：Appropriate pretreated vegetable oil is taken, glycerin monostearate heating fusing is added, suspending agent, Cefquinome sulfate is subsequently adding, then adds vegetable oil to full dose, grinding is uniform, obtains final product.The breast injection has the following advantages that：Insoluble drug release is slow, and bioavilability is high, small 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, for clinical application provides facility；It is evident in efficacy, with high promotional value.
Description
Technical field
The present invention relates to a kind of Cefquinome sulfate breast injection（Lactation period）And preparation method thereof.
Background technology
Recently as the continuous adjustment of cultivation structure, the milk cow production of China has obtained tremendous development in scale,
But the mastitis for milk cows incidence of disease aborning is very high, it is by based on staphylococcus aureus, streptococcus, Escherichia coli etc.
A kind of microbial frequently-occurring disease of cause of disease and stubborn disease are wanted, sees that infected cattle spirit is depressed, body temperature is raised, appetite is useless exhausted in clinic；
Lactation reduction, milk are thin, touch breast heating and red and swollen sense, and milk includes floccule or curdling block etc., causes the output of milk
With milk-quality reduction, the sound development of dairy is had a strong impact on, this disease not only causes great economic loss to aquaculture, and
And the also health of the serious harm mankind.Therefore, the preventing and treating to mastitis for milk cows is particularly important.
Cefquinome (Cefquinome), is also called HOE 111 or Cefquinome, is the forth generation cephalo of animal specific
Bacteriums antibiotic.Synthesis of the Cefquinome by suppressing cell membrane reaches bactericidal effect, and its has a broad antifungal spectrum, antibacterial activity are strong,
Good antibacterial activity is shown to most of G+ bacterium and G- bacterium, especially to staphylococcus aureus, streptococcus, Pseudomonas aeruginosa
There is relatively low Mlc with the member of Colibacter, the staphylococcus and enterococcus to penicillin resistant also have work in addition
Property.Cefquinome is highly stable to beta-lactamase.Cefquinome is registered in China, is mainly used in treatment killing property Pasteur's bars more
The porcine respiratory disease that bacterium or Actinobacillus pleuropneumoniae cause.
Existing Cefquinome sulfate injection, powder-injection mainly by administered intramuscular, are extremely difficult to internal mammary,
Be not as good as breast local application effect.Therefore, a kind of Cefquinome preparation used suitable for the Lactation of Dairy Cow phase is developed with weight
The realistic meaning wanted.
The content of the invention
It is an object of the invention to provide a kind of Cefquinome sulfate breast injection（Lactation period）And preparation method thereof.
Cefquinome sulfate breast injection provided by the present invention（Lactation period）, it is made up of following supplementary materials：Sulfuric acid head
Spore quinoline oxime（Bulk drug）0.05-0.15g（In terms of Cefquinome）, glycerin monostearate 0.008-0.08g, suspending agent 0.008-
0.08g, vegetable oil add to 8.0g.
The Cefquinome sulfate breast injection（Lactation period）Further can be made up of following supplementary materials：Sulfuric acid cephalo quinoline
Oxime（Bulk drug）0.075-0.15g（In terms of Cefquinome）, glycerin monostearate 0.008-0.08g, suspending agent 0.008-
0.08g, vegetable oil add to 8.0g.
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 cefquinome sulfate raw material medicine can be 5-10 μm.
The proterties of Cefquinome sulfate breast injection of the present invention is off-white color to faint yellow oleagenous suspension.
The preparation method of above-mentioned Cefquinome sulfate breast injection, by vegetable oil, glycerin monostearate and suspending agent
Macromolecular compound dicyandiamide solution is made, then the aseptic micro mist of Cefquinome sulfate is added, continued agitation grinding and be made sulfuric acid
Cefquinome breast injection.
Specific preparation method comprises the following steps：
1）After appropriate vegetable oil and glycerin monostearate are mixed, heating fusing obtains mixed system（That is producing high-molecular
Compound dicyandiamide solution）；
2）To addition suspending agent, Cefquinome sulfate in the mixed system, then add vegetable oil to full dose, grinding is uniform,
Obtain final product the Cefquinome sulfate breast injection（Lactation period）.
Wherein, step 1）Described in heat condition 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 be carried out in colloid mill.
The vegetable oil is using the preceding pretreatment also needed by filtering and heat sterilization.The condition of the heat sterilization
For：150-160 DEG C sterilizes 2-3 hours.
Cefquinome sulfate breast injection provided by the present invention has significant curative effect to Lactation of Dairy Cow phase mammitis.Sulphur
Sour Cefquinome breast injection (lactation period) be clinically used for treat mastitis for milk cows consumption be：1 (8g:75mg)/breast
Area time, is spaced 12 hours/time, is used in conjunction 3 times.
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 small, 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, and bioavilability is high, to tissue irritation for this preparation
Low, clinical efficacy is notable, 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, unless otherwise specified, is conventional method；The reagent and material, such as
Without specified otherwise, can be obtained by commercial sources.
The Cefquinome sulfate breast injection that the present invention is provided is a kind of preparation being evenly distributed, specific preparation method bag
Include following steps：
A. by vegetable oil（Such as neutral soybean oil）Through being let cool after filtering and heat sterilization；
B takes appropriate pretreated vegetable oil, adds the glycerin monostearate of 0008-008g；
C.60~80 DEG C heating 15~30 minutes, treat that tristerin melts, and after stirring, are cooled to 40 DEG C of left sides
The right side, adds the suspending agent of 0.008-0.08g（Such as sorbester p17）、0.05-0.15g（In terms of Cefquinome）Cefquinome sulfate
（5-10 μm of particle diameter）, then it is 8.0g to add vegetable oil to total amount；
D. grind uniform, Cefquinome sulfate breast injection is obtained；
F. medicine is fitted into injecting pipe, sealing, sterilizing, lamp inspection, packaging.
To the detection method of the sedimentation granularity of breast injection in following embodiments：Apparatus plug graduated cylinder takes test sample 50ml,
Close plug, firmly shakes 1 minute, writes down the beginning height H0 of suspension, stands 3 hours, writes down the final height H of suspended matter, presses
Following formula is calculated, 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：
This product 11 is taken, peptone buffering sterile solutions of the 400ml containing 6% Tween-80 is added to（0.1%）In, it is fully mixed
It is even, add penicillase（No less than 66,000,000 units）, it is well mixed, put 37 DEG C and be incubated 4 hours；Need testing solution is taken, in accordance with the law
Check（Annex page 137, direct inoculation）, regulation should be met.
The prescription screening of embodiment 1, Cefquinome sulfate breast injection
1st, in prescription glycerin monostearate content screening（Note：Glycerin monostearate abbreviation glyceride in table）
Table 1
Preparation method is as follows：
1）Cefquinome sulfate aseptic powder is obtained into the aseptic micro mist of Cefquinome sulfate through ultramicro grinding（5-10 μm of particle diameter）；
2）By soybean oil through filtering and heat sterilization（150 DEG C sterilize 3 hours）Afterwards, it is placed in standby at room temperature；
3）Appropriate pretreated soybean oil is taken, tristerin and suspending agent sorbester p17 is added；Heat and stir
（80 DEG C heat 15 minutes）, after treating that tristerin melts, add Cefquinome sulfate；
5）Grind uniform in aseptic colloid mill, Cefquinome sulfate breast injection is obtained.
As seen from the results in Table 1, when the content of glycerin monostearate is 0.05% (w/w), the sedimentation index of product is not up to
To the requirement of quality standard；When the content of glycerin monostearate is 0.1~1.0% (w/w), the indices of product have reached
The full requirement for meeting quality standard, it is thus determined that the content of glycerin monostearate is 0.1~1% (w/w) in prescription.
2nd, in prescription Arlacel-80 content screening
Table 2
Preparation method is ibid.
As seen from the results in Table 2, when the content of Arlacel-80 is 0.05% (w/w), the sedimentation index of product does not reach quality
The requirement of standard；When the mass content of Arlacel-80 is 0.1~1% (w/w), the indices of product reach and comply fully with quality mark
Accurate requirement, it is thus determined that Arlacel-80 content is 0.1~1% (w/w) in prescription.
Embodiment 2, prepare Cefquinome sulfate breast injection（Lactation period）
Preparation method is as follows：
1）Cefquinome sulfate aseptic powder is obtained into the particle diameter aseptic micro mist of 5-10 μm of Cefquinome sulfate through ultramicro grinding；
2）By soybean oil through filtering and heat sterilization（150 DEG C sterilize 3 hours）Afterwards, it is placed in standby at room temperature；
3）Take appropriate pretreated soybean oil（It is the 40%-60% of the total consumption of soybean oil）, add glycerin monostearate；
Heat and stir（80 DEG C heat 15 minutes）, treat that glycerin monostearate melts, after stirring, it is cooled to 40 DEG C, addition department
Disk 80, Cefquinome sulfate, then increase soya-bean oil to full dose；
4）Grind uniform in aseptic colloid mill, Cefquinome sulfate breast injection is obtained.
Gained Cefquinome sulfate breast injection（Lactation period）Proterties be off-white color to faint yellow oleagenous suspension.
The said goods are carried out to settle granularity and Sterility testing, its quality standard for meeting breast injection.
Embodiment 3, prepare Cefquinome sulfate breast injection（Lactation period）
Preparation method is as follows：
1）Cefquinome sulfate aseptic powder is obtained into the particle diameter aseptic micro mist of 5-10 μm of Cefquinome sulfate through ultramicro grinding；
2）By soybean oil through filtering and heat sterilization（150 DEG C sterilize 3 hours）Afterwards, it is placed in standby at room temperature；
3）Take appropriate pretreated soybean oil（It is the 40%-60% of the total consumption of soybean oil）, add glycerin monostearate；
Heat and stir（80 DEG C heat 15 minutes）, treat that glycerin monostearate melts, after stirring, it is cooled to 40 DEG C, addition department
Disk 80, Cefquinome sulfate, then increase soya-bean oil to full dose；
4）Grind uniform in aseptic colloid mill, Cefquinome sulfate breast injection is obtained.
The proterties of gained Cefquinome sulfate breast injection is off-white color to faint yellow oleagenous suspension.
The said goods are carried out to settle granularity and Sterility testing, its quality standard for meeting breast injection.
Embodiment 4, prepare Cefquinome sulfate breast injection（Lactation period）
Preparation method is as follows：
1）Cefquinome sulfate aseptic powder is obtained into the particle diameter aseptic micro mist of 5-10 μm of Cefquinome sulfate through ultramicro grinding；
2）By tea oil through filtering and heat sterilization（160 DEG C sterilize 2 hours）Afterwards, it is placed in standby at room temperature；
3）Take appropriate pretreated tea oil（It is the 40%-60% of the total consumption of tea oil）, add glycerin monostearate；Heating
And stir（60 DEG C heat 30 minutes）, treat that glycerin monostearate melts, after stirring, be cooled to 40 DEG C, add sorbester p17,
Cefquinome sulfate, then increase soya-bean oil to full dose；
4）Grind uniform in aseptic colloid mill, Cefquinome sulfate breast injection is obtained.
The proterties of gained Cefquinome sulfate breast injection is off-white color to faint yellow oleagenous suspension.
The said goods are carried out to settle granularity and Sterility testing, its quality standard for meeting breast injection.
Embodiment 5, prepare Cefquinome sulfate breast injection（Lactation period）
Preparation method is as follows：
1）Cefquinome sulfate aseptic powder is obtained into the particle diameter aseptic micro mist of 5-10 μm of Cefquinome sulfate through ultramicro grinding；
2）By corn oil through filtering and heat sterilization（150 DEG C sterilize 2 hours）Afterwards, it is placed in standby at room temperature；
3）Take appropriate pretreated corn oil（It is the 40%-60% of the total consumption of corn oil）, add glycerin monostearate；
Heat and stir（80 DEG C heat 30 minutes）, treat that glycerin monostearate melts, after stirring, 40 DEG C are cooled to, addition is told
Temperature -80, Cefquinome sulfate, then increase soya-bean oil to full dose；
4）Grind uniform in aseptic colloid mill, Cefquinome sulfate breast injection is obtained.
The proterties of gained Cefquinome sulfate breast injection is off-white color to faint yellow oleagenous suspension.
The said goods are carried out to settle granularity and Sterility testing, its quality standard for meeting breast injection.
Embodiment 6, prepare Cefquinome sulfate breast injection（Lactation period）
Preparation method is as follows：
1）Cefquinome sulfate aseptic powder is obtained into the particle diameter aseptic micro mist of 5-10 μm of Cefquinome sulfate through ultramicro grinding；
2）By cottonseed oil through filtering and heat sterilization（150 DEG C sterilize 2 hours）Afterwards, it is placed in standby at room temperature；
3）Take appropriate pretreated cottonseed oil（It is the 40%-60% of the total consumption of cottonseed oil）, add glycerin monostearate；
Heat and stir（80 DEG C heat 15 minutes）, treat that glycerin monostearate melts, after stirring, 40 DEG C are cooled to, add big
Fabaceous Lecithin, Cefquinome sulfate, then increase soya-bean oil to full dose；
5）Grind uniform in aseptic colloid mill, Cefquinome sulfate breast injection is obtained.
The proterties of gained Cefquinome sulfate breast injection is off-white color to faint yellow oleagenous suspension.
The said goods are carried out to settle granularity and Sterility testing, its quality standard for meeting breast injection.
Embodiment 7, Cefquinome sulfate breast injection（Lactation period）Vivo efficacy experiment
1）Cefquinome sulfate breast injection（Lactation period）To the safety testing of milk cow
Experiment randomly selects 12 healthy lactating cows（6 primiparity, 6 through producing）, four Ge Ru areas are injected separately into embodiment 3
The Cefquinome sulfate breast injection of preparation（Lactation period）One（Specification 75mg：8g）, it is spaced and is administered once for 12 hours, continuously
Administration 3 times.
Before administration 24h and administration before 0h；After 1st administration and after the 3rd administration；After drug withdrawal the 2nd day and be discontinued after the 3rd
My god；After drug withdrawal the 6th day and be discontinued after the 7th day collection milk sample, every Niu Sigeru area individually gathers, after squeezing out first three milk
Collection about 30mL milk samples carry out SCC detections and bacteria distribution identification in 50mL sterilizing polypropylene centrifuge tubes.During sampling, observation
The clinical symptoms change, statistics such as the breast local symptom of recording medicine milk cow, milking capacity and milk proterties, spiritual appetite state
Milk cow daily yielding.Compare the significance of difference of the front and rear above index of administration, peace of the overall merit said preparation to milk cow in lactation period
Quan Xing.
Result shows, test medicine Cefquinome sulfate breast injection（Lactation period）In the administration with drug withdrawal after with administration
All without conspicuousness on the separation qualification result of somatic number and bacterium in clinical manifestation scoring, daily yielding, the milk of preceding milk cow
Difference.Illustrate that milk cow in lactation period gives Cefquinome sulfate breast injection by recommended dose（Lactation period）It is to milk cow in lactation period
Safety.
2）Cefquinome sulfate breast injection（Lactation period）Tested in the pharmacokinetics of cow's milk
6 healthy lactating cows are chosen, after squeezed milk in the morning, every Niu Sigeru area selects one, bolus injection reality at random
Apply example 3 and prepare Cefquinome sulfate breast injection（Lactation period）One（Specification 75mg：8g）.Mined out white milk sample before administration,
The newborn area of 0.25h, 0.5h, 0.75h, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h administration upon administration
Collection milk sample 40-50ml；Non-administration breast area 2h, 6h, 12h, 24h collection milk sample 40- respectively after the newborn area's administration of administration
50ml（Notice that first three milk can not be given up）, it is placed in polypropylene special plastic bottle, sealing, -20 DEG C of freezen protectives are to be measured.Respectively
Head experiment milk cow is adopted respectively at 2h, 6h, 12h, 24h after 0h, administration, jugular vein blood collection 10-15ml, injection EDTAK2 vacuum anti-freezings
In blood vessel.Centrifugation, separated plasma is to be measured in -20 DEG C of freezen protectives.
Using the UPLC-MS/MS detection sides of Cefquinome sulfate in Cefquinome sulfate in the cow's milk set up and blood plasma
Method detects the medicament contg in gathered milk sample and plasma sample respectively.Specifically detection method is：Milk sample 1g is weighed,
It is placed in 15ml polypropylene centrifuge tubes.Acetonitrile 3ml vortexs 1min, 8000rpm centrifugation 10min is added, supernatant to 10ml is pipetted
In teat glass, residual residue addition 2ml acetonitriles carry out second extraction, and vortex 1min, 8000rpm centrifugation 10min merges two
Secondary extract solution, nitrogen blows and is concentrated to dryness under 40 DEG C of water-baths.Residue 3ml water redissolves, and redissolves liquid and crosses HLB solid phase extraction columns（HLB
Activated through 3mL methyl alcohol in advance, 3mL water balances）, then with 3mL5% methyl alcohol water washing HLB solid phase extraction columns, finally use 1.5mL first
Alcohol is eluted, and collection eluent is in 10mL teat glasses.Eluent nitrogen under 40 DEG C of water-baths blows and is concentrated to dryness, residue mobile phase
The aqueous formic acid of 1mL acetonitriles -0.1%（5:95, V/V）Redissolve, whirling motion 1min, make on centrifugation tube wall after the dissolving of residue whole, mistake
0.2 μm of filter membrane is detected in sample introduction bottle using LC-MS instrument.
Result shows that medicine only has detection in the newborn area of administration, and non-administration breast area detects without pharmaceutical compositions, also only examined in blood plasma
Go out trace drug ingedient, and the 24th hour blood plasma drug concentration has been less than method detection limit upon administration.Illustrate medicine almost
Blood circulation system cannot be entered through blood breast barrier, only antibacterial action is played in the newborn area of administration.Software is processed using pharmacokinetics
The non-compartment models of WinNonLin6.1 are processed and calculate relevant pharmacokinetic parameter.Result display medicine eliminates fast in breast
Speed, elimination half-life period T1/2 is 5.91 ± 0.83h, and TG-AUC AUC is 309997.54 ± 34553.82hng/mL, is disappeared
Removal rates constant Cl is 0.61 ± 0.07ml/h/kg.With reference to the MIC data reported, the drug concentration as 12h can be whole
Higher than Cefquinome sulfate to the MIC numerical value of mammitis Main Pathogenic Bacteria, be during 24h part higher than Cefquinome sulfate to breast
The MIC numerical value of room inflammation Main Pathogenic Bacteria, therefore, it is suggested that dosing interval was administered once for 12 hours.
3）Cefquinome sulfate breast injection（Lactation period）In the residue test of cow's milk
Randomly select 18 healthy lactating cows（High, medium and low product is each 6）, after having squeezed milk, every Niu Sigeru area, point
Not Zhu Ru embodiment 3 prepare Cefquinome sulfate breast injection（Lactation period）One（Specification 75mg：8g）, interval 12h administrations
Once, successive administration 3 times.
Mined out white milk sample before administration, 12h after the administration is complete, 18h, 24h, 36h, 42h, 48h, 60h, 66h, 72h,
84h, 90h, 96h, 108h, 114h, 120h gather milk sample.Each time point every Niu Sigeru area, collection composite sample 40-50ml
（First three milk can not be given up when noting milking）, it is placed in polypropylene special plastic bottle, -20 DEG C of preservations.Milk sample is through acetonitrile twice
Nitrogen drying after extraction, crosses the purification of HLB solid phase extraction columns after redissolution, dense using medicine in UPLC-MS/MS methods detection cow's milk
Degree.Cefquinome eliminates rapid in cow's milk after result display administration, and 60 hours newborn drug concentrations have been less than EMEA institutes after administration
MRL in regulation breast（MRL）20ug/kg, after being processed through off-drug period software for calculation WT1.4, this preparation is in cow's milk
Off-drug period is 93.41 hours.
4）Cefquinome sulfate breast injection（Lactation period）To the pharmacodynamics test of mastitis for milk cows
The milk cow of mammitis is suffered from this experimental animal selection only one of which breast area, altogether 80 cases（80 ill breast districts）,
It is randomly divided into 4 groups, every group of 20 ill breast districts.3 test medicine groups（I, II, III), respectively Cefquinome sulfate breast
Injectant high dose（Group I, 2/breast area）Group, middle dosage（Group II, 1/breast area）Group；Low dosage（Group III, 1/2/breast area）
Group；1 control drug group（IV groups）, it is ampicillin sodium, Cloxacillin Sodium breast injection (lactation period)（Organize IV, 1/breast
Area）Group.Above-mentioned Cefquinome sulfate breast injection is sample prepared by embodiment 3, and specification is 75mg：8g.
Test medicine high dose group injects 2 Cefquinome sulfate breast injections to the newborn area of each infection；Middle dose group to
1 Cefquinome sulfate breast injection is injected in each newborn area of infection；Low dose group injects 1/2 sulfuric acid cephalo to the newborn area of each infection
Quinoline oxime breast injection；Control drug group injects 1 ampicillin sodium, Cloxacillin Sodium breast injection to the newborn area of each infection
(lactation period).All test group animals are administered daily 2 times（Interval 12 hours）, it is used in conjunction 3 times.Give before administration and for the last time
The 7th day after medicine, the milk sample 20mL that each newborn area of test group administration is gathered respectively carries out bacteriology checking and milk somatic cell measure.Examine
Examine spiritual appetite state before and after milk cow medication, breast local clinical symptom, milking capacity and milk proterties, overall merit sulfuric acid
Curative effect of the Cefquinome breast injection to mastitis for milk cows.
Through statistical analysis after experiment, can be drawn a conclusion：
（1）Detection of pathogens result shows（It is shown in Table 1）, infection breast area's perfusion Cefquinome sulfate breast of mammitis milk cow
Injectant (lactation period), early daily, evening is each 1 time, high after continuous use 3 times（2 times of recommended doses）, in（Recommended dose）Dosage
Bacterium respectively from before administration 23 plants and 26 plants are reduced to administration in Cefquinome sulfate breast injection (lactation period) group cow's milk
3 plants afterwards and 6 plants；It is low（1/2 recommended dose）Dosage Cefquinome sulfate breast injection (lactation period) is organized and control drug ammonia
Bacterium 25 plants and 25 plants reductions respectively from before administration in benzyl XiLin sodium, Cloxacillin Sodium breast injection (lactation period) group cow's milk
15 plants after to administration and 18 plants.Illustrate Cefquinome sulfate breast injection (lactation period) high dose group and middle dose group to milk
Garget Main Pathogenic Bacteria has good scavenging action, better than Cefquinome sulfate breast injection (lactation period) low dose group
With control drug ampicillin sodium, Cloxacillin Sodium breast injection (lactation period) group to the clear of main pathogen of bovine mastitis
Except effect.
The separation qualification result statistics of the main pathogenic fungi before and after table 1, each test group milk cow's milk area's medication
（2）Cefquinome sulfate breast injection (lactation period) and control drug ampicillin sodium, Cloxacillin Sodium breast
Injectant (lactation period) is to milk somatic cell number（It is shown in Table 2）Reduction have obvious therapeutic effect, each group somatic number is substantially reduced
（P ＜ 0.05), indifference conspicuousness between each group（P ＞ 0.05）.It is significantly excellent after each test group symptom scores numerical value administration
In before administration（P ＜ 0.05）, middle high dose group is significantly better than low dose group and control group（P ＜ 0.05）.It is high（2 times of recommendation agent
Amount）, in（Recommended dose）The spiritual appetite of milk cow, breast office after dosage Cefquinome sulfate breast injection (lactation period) treatment
The mammitis clinical symptoms such as portion's symptom and milk proterties are obtained for and significantly improve（It is shown in Table 3）, effect is significant is better than ampicillin
Sodium, Cloxacillin Sodium breast injection (lactation period) group and low dosage Cefquinome sulfate breast injection (lactation period) group（P ＜
0.05）.High, medium and low dosage respectively reaches 90%, 80%, 65% to the effective percentage of mastitis for milk cows, cure rate respectively reaches 80%,
75%、35%（It is shown in Table 4）, ampicillin sodium, Cloxacillin Sodium breast injection (lactation period)（IV groups）Have to mastitis for milk cows
Efficiency is 55%, and cure rate is 50%.Wherein low dosage（1/2 times of recommended dose）To mastitis for milk cows effective percentage and cure rate with
Ampicillin sodium, Cloxacillin Sodium breast injection (lactation period) are without significant difference（P ＞ 0.05）, high, middle dosage is to milk cow's milk
The scorching effective percentage in room and the cure rate difference compared with control group ampicillin sodium, Cloxacillin Sodium breast injection (lactation period) show
Write（P ＜ 0.05）, and the high, curative effect of middle dosage is without significant difference（P ＞ 0.05）.
Respectively the newborn area's milk sample for the treatment of is administered front and rear Somatic Cell Count (SCC) statistics to table 2
The newborn area's symptom score result of the mastitis for milk cows of table 3 administration
Note：Each data are the average in Zu Neigeru areas in table
* represent each group medication before with after medication scoring compared with significant difference（P ＜ 0.05）
a、b：Represent that difference is not notable between same letter（P ＞ 0.05）, significant difference is represented between difference is alphabetical（P ＜ 0.05）
The cure rate and effective percentage of the test medicine of table 4 and control drug to mastitis for milk cows
Note：a、b、c：There is same letter to represent that difference is not notable（P ＞ 0.05）, there is no same letter to represent significant difference（P
＜ 0.05）.
（3）In view of height（2 times of recommended doses）, in（Recommended dose）Dosage Cefquinome sulfate breast injection (lactation
Phase) to the curative effect of mastitis for milk cows（Pathogen elimination effect, clinical symptoms recovery situation）Difference is not notable, is superior to low dosage
（1/2 times of recommended dose）Group, therefore recommend Cefquinome sulfate breast injection (lactation period) to be clinically used for preventing and treating cow breast
Scorching therapeutic regimen is：1 (8g:75mg)/newborn area time, is spaced 12 hours/time, is used in conjunction 3 times.
The method that vivo efficacy according to embodiment 7 is tested carries out identical test to the product of embodiment 2,4,5,6, its
Result is suitable with the effect of embodiment 3.The Cefquinome sulfate breast injection of present invention offer is provided（Lactation period）Safety has
Effect, bioavilability are high, small to local tissue stimulation, evident in efficacy, with high promotional value.
Claims (8)
1. a kind of Cefquinome sulfate breast injection, is made up of following supplementary materials：Cefquinome sulfate 0.05-0.15g, list are hard
Glycerol 0.008-0.08g, suspending agent 0.008-0.08g, vegetable oil add to 8.0g；The quality of the Cefquinome sulfate
In terms of Cefquinome；
The particle diameter of the Cefquinome sulfate is 5-10 μm；
The suspending agent is selected from following at least one：Tween 80, sorbester p17 and soybean lecithin；
The Cefquinome sulfate breast injection is used for the prevention and/or treatment of Lactation of Dairy Cow phase mammitis；
The Cefquinome sulfate breast injection is prepared according to the method for comprising the steps：
1) after mixing the appropriate vegetable oil and the glycerin monostearate, heating fusing obtains mixed system；
The consumption of the vegetable oil is the 40%-60% of vegetable oil total amount；
2) to adding the suspending agent, the Cefquinome sulfate in the mixed system, then vegetable oil to full dose is added, grinding is equal
It is even, obtain final product the Cefquinome sulfate breast injection；
2. breast injection according to claim 1, it is characterised in that：The Cefquinome sulfate breast injection is under
Supplementary material is stated to be made：Cefquinome sulfate 0.075-0.15g, glycerin monostearate 0.008-0.08g, suspending agent 0.008-
0.08g, vegetable oil add to 8.0g；The quality of the Cefquinome sulfate is in terms of Cefquinome.
3. breast injection according to claim 1 and 2, it is characterised in that：The vegetable oil is selected from following at least one：
Soybean oil, tea oil, corn oil, peanut oil and cottonseed oil.
4. breast injection according to claim 3, it is characterised in that：The vegetable oil is soybean oil.
5. breast injection according to claim 4, it is characterised in that：The suspending agent is sorbester p17.
6. breast injection according to claim 5, it is characterised in that：Step 1) described in heat condition be：60~
80 DEG C heat 15~30 minutes；Step 2) described in grind and carried out in colloid mill.
7. breast injection according to claim 6, it is characterised in that：The vegetable oil is also needed by filtering using preceding
And the pretreatment of heat sterilization；The condition of the heat sterilization is：150-160 DEG C sterilizes 2-3 hours.
8. Cefquinome sulfate breast injection any one of claim 1-7 is secreted in preparation prevention and/or treatment milk cow
Application in newborn phase mammitis medicine.
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| CN201310664982.XA CN104546703B (en) | 2013-12-10 | 2013-12-10 | A kind of Lactation of Dairy Cow phase is with Cefquinome sulfate breast injection and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105079000B (en) * | 2015-09-22 | 2018-07-06 | 佛山市南海东方澳龙制药有限公司 | A kind of composition and its application, preparation |
| CN105287374A (en) * | 2015-12-07 | 2016-02-03 | 中牧南京动物药业有限公司 | Preparation method of cefquinome sulfate breast injectant and obtained preparation |
| CN105796491A (en) * | 2016-03-30 | 2016-07-27 | 佛山市南海东方澳龙制药有限公司 | Composition, application of composition, and preparation comprising composition |
| CN107789357A (en) * | 2016-08-31 | 2018-03-13 | 瑞普（天津）生物药业有限公司 | A kind of animal compound Cefquinome sulfate breast injection and preparation method thereof |
| CN107157927A (en) * | 2017-05-31 | 2017-09-15 | 合肥中龙神力动物药业有限公司 | Animal cefquinome sulfate injection and preparation method thereof |
| CN114869850B (en) * | 2022-06-20 | 2023-04-28 | 山东晟阳生物工程有限公司 | Cefquinome sulfate injection |
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