CN104546704A - Ceftiofur hydrochloride breast injection for dairy cow in dry period and preparation method thereof - Google Patents
Ceftiofur hydrochloride breast injection for dairy cow in dry period and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a ceftiofur hydrochloride breast injection for dairy cow in dry period and a preparation method thereof. The injection is prepared from the following raw and auxiliary materials: 2.5-10g of ceftiofur hydrochloride, 0.5-5g of glyceryl monostearate, 0.5-5g of a suspending agent and the balance of vegetable oil which is added until the total amount is 100ml. The preparation method comprises the following steps: mixing a proper amount of vegetable oil and glyceryl monostearate, heating and melting; then adding the suspending agent and ceftiofur hydrochloride, and adding the vegetable oil until total amount; and uniformly grinding to prepare the ceftiofur hydrochloride breast injection. The breast injection has the advantages of low drug release speed, high bioavailability and small irritation to local tissues; each lactation region of each dairy cow is independently administrated, so that cross infection is avoided; the injection is injected through breast and is convenient to use, so that animal stress reaction caused by parenteral administration can be avoided, and convenience is brought to clinical administration; the injection has a remarkable curative effect and extremely high popularization 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-type antibiotics of animal specific.Has a broad antifungal spectrum, the antibacterial activity of ceftiofur are strong, all have extremely strong antibacterial activity to gram positive bacteria, gram negative bacteria and some anaerobe; And there is stable beta-lactam nucleus, also there is good killing effect for the various antibacterial that can produce beta-lactamase, not easily produce Resistant strain and cross resistance, be mainly used in the responsive microbial various infection of many animals clinically.Therefore, ceftiofur treatment livestock and poultry is applied significant.
Now the ceftiofur dosage form of research both at home and abroad has the dosage forms such as injection ceftiofur sodium injection, ceftiofur sodium lipidosome, and the shortcoming of these dosage forms is that action time is short, and its administrated method is injection every day once substantially, is used in conjunction 3 ~ 5 days.Therefore, develop that a kind of drug release is slow, bioavailability is high and be applicable to milch cow and do the ceftiofur formulation that the breast phase uses and have important practical significance.
Summary of the invention
The object of this invention is 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), is made up of following supplementary material: Ceftiofur Hydrochloride (crude drug) 2.5-10g, glyceryl monostearate 0.5-5g, suspending agent 0.5-5g, vegetable oil add to 100ml.
Described Ceftiofur Hydrochloride breast injection can be made up of following supplementary material further: Ceftiofur Hydrochloride (crude drug) 5g, glyceryl monostearate 0.5-5g, suspending agent 0.5-5g, vegetable oil add to 100ml.
Wherein, described vegetable oil specifically can be selected from following at least one: soybean oil, Oleum Camelliae, Semen Maydis oil, Oleum Arachidis hypogaeae semen and Oleum Gossypii semen.Described vegetable oil can be soybean oil further.
Described suspending agent specifically can be selected from following at least one: Tween 80, sorbester p17 and soybean phospholipid.Described suspending agent can be sorbester p17 further.
The particle diameter of described Ceftiofur Hydrochloride crude drug can be 5-10 μm.
The character of Ceftiofur Hydrochloride breast injection of the present invention is that off-white color is to yellow oil suspension.
The preparation method of above-mentioned Ceftiofur Hydrochloride breast injection, macromolecular compound dicyandiamide solution is made by vegetable oil, glyceryl monostearate and suspending agent, added by the aseptic micropowder of Ceftiofur Hydrochloride, Ceftiofur Hydrochloride breast injection is made in Keep agitation grinding again.
Concrete preparation method comprises the steps:
1) by after appropriate vegetable oil and glyceryl monostearate mixing, heat fused, obtains mixed system (i.e. macromolecular compound dicyandiamide solution);
2) in described mixed system, add suspending agent, Ceftiofur Hydrochloride, then add vegetable oil to full dose, grinding evenly, obtains described Ceftiofur Hydrochloride breast injection (dry breast phase).
Wherein, the condition heated described in step 1) is: heat 15 ~ 30 minutes for 60 ~ 80 DEG C.The 40%-60% that the consumption of the vegetable oil used in step 1) is under normal circumstances vegetable oil total amount.
Step 2) described in grind and can carry out in colloid mill.
Described vegetable oil also needs the pretreatment through filtration and heat sterilization before use.The condition of described heat sterilization is: 150-160 DEG C of sterilizing 2-3 hour.
Ceftiofur Hydrochloride breast injection provided by the present invention (dry breast phase) has significant curative effect to milch cow dry breast phase mastitis.
Compared with prior art, the present invention has following beneficial effect:
(1) convenient drug administration is quick, decreases a large amount of manpower and materials;
(2) Animal stress reaction is little, reduces the damage of animal body;
(3) production technology is simple, and the preparation obtained is even, dispersibility, good stability, is easy to extension and produces;
(4) every cattle independent medication in each newborn district, namely independently uses medical apparatus and instruments (preparation), avoids cross infection;
(5) this preparation is for injection, and drug release is slow, and bioavailability is high, to local tissue stimulation
Property low, clinical efficacy is remarkable, has high promotional value.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is further illustrated, but the present invention is not limited thereto.
Experimental technique described in following embodiment, if no special instructions, is conventional method; Described reagent and material, if no special instructions, all obtain by commercial sources.
Ceftiofur Hydrochloride breast injection provided by the invention is a kind of preparation be evenly distributed, and concrete preparation method comprises the following steps:
A. vegetable oil (as neutral soybean oil) is let cool after filtration with after heat sterilization;
B. get appropriate pretreated vegetable oil, add the glyceryl monostearate of 0.5 ~ 5g;
C.60 heat 15 ~ 30 minutes for ~ 80 DEG C, treat that glyceryl monostearate melts, after stirring, be cooled to about 40 DEG C, add the Ceftiofur Hydrochloride (particle diameter 5-10 μm) of the suspending agent (as sorbester p17) of 0.5 ~ 5g, 2.5 ~ 10g, then to add vegetable oil to total amount be 100ml;
D. grinding evenly, obtained Ceftiofur Hydrochloride breast injection;
E. being loaded by medicine injects in pipe, sealing, sterilizing, lamp inspection, packaging.
In following embodiment to the detection method of the sedimentation granularity of breast injection be: test sample 50ml got by apparatus plug graduated cylinder, close plug, firmly jolting 1 minute, write down the beginning height H 0 of suspension, leave standstill 3 hours, write down the final height H of suspended matter, be calculated as follows, result is as follows: settling ratio volume F=H/H0, and it is 0.90 that is qualified to be not less than.
The method of steriling test is: get this product 10, often prop up 10ml(with front shaking up), after mixing, get 25ml, add aseptic 1% tween 80 and 0.1% peptone solution 250ml, shake well makes dispersion, add penicillinase solution (every 1mg Ceftiofur Hydrochloride adds penicillinase about 14400 unit), shake well 30 minutes, mixing, get mixed liquor 10ml, add in 100ml THIOGLYCOLLIC ACID salt broth and improvement Martin culture medium respectively, under corresponding conditions, shaking table cultivates 14, getting culture fluid is inoculated on slant medium, antibacterial culturing 2 days, fungal culture 3 days, check (annex 137 pages) in accordance with the law, result should conform with the regulations.
Embodiment 1, prepare Ceftiofur Hydrochloride breast injection (dry breast phase)
Preparation method is as follows:
1) Ceftiofur Hydrochloride aseptic powder is obtained the aseptic micropowder of particle diameter 5-10 μm Ceftiofur Hydrochloride through micronizing;
2) by soybean oil after filtration with heat sterilization (160 DEG C sterilizing 2 hours) after, for subsequent use under being placed in room temperature;
3) get appropriate pretreated soybean oil (40%-60% for the total consumption of soybean oil), add glyceryl monostearate; Heat and stir (heating 15 minutes for 60 DEG C), treating that glyceryl monostearate melts, after stirring, be cooled to 40 DEG C, then add sorbester p17, Ceftiofur Hydrochloride, then with soybean oil to full dose;
4) in aseptic colloid mill, grinding evenly, obtains Ceftiofur Hydrochloride breast injection.
The character of gained Ceftiofur Hydrochloride breast injection (dry breast phase) is that off-white color is to yellow oil suspension.
Carry out sedimentation granularity and Sterility testing to the said goods, it all 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 is obtained the aseptic micropowder of particle diameter 5-10 μm Ceftiofur Hydrochloride through micronizing;
2) by soybean oil after filtration with heat sterilization (150 DEG C sterilizing 3 hours) after, for subsequent use under being placed in room temperature;
3) get appropriate pretreated soybean oil (40%-60% for the total consumption of soybean oil), add glyceryl monostearate; Heat and stir (heating 30 minutes for 80 DEG C), treating that glyceryl monostearate melts, after stirring, be cooled to 40 DEG C, then add sorbester p17, Ceftiofur Hydrochloride, then with soybean oil to full dose;
4) in aseptic colloid mill, grinding evenly, obtains Ceftiofur Hydrochloride breast injection.
The character of gained Ceftiofur Hydrochloride breast injection (dry breast phase) is that off-white color is to yellow oil suspension.
Carry out sedimentation granularity and Sterility testing to the said goods, it all meets the quality standard of breast injection.
Embodiment 3, prepare Ceftiofur Hydrochloride breast injection
Preparation method is with embodiment 2.
The character of gained Ceftiofur Hydrochloride breast injection is that off-white color is to yellow oil suspension.
Carry out sedimentation granularity and Sterility testing to the said goods, it all meets the quality standard of breast injection.
Embodiment 4, prepare Ceftiofur Hydrochloride breast injection
Preparation method is with embodiment 2.
The character of gained Ceftiofur Hydrochloride breast injection is that off-white color is to yellow oil suspension.
Carry out sedimentation granularity and Sterility testing to the said goods, it all meets the quality standard of breast injection.
Embodiment 5, prepare Ceftiofur Hydrochloride breast injection
Preparation method is with embodiment 2.
The character of gained Ceftiofur Hydrochloride breast injection is that off-white color is to yellow oil suspension.
Carry out sedimentation granularity and Sterility testing to the said goods, it all meets the quality standard of breast injection.
Embodiment 6, prepare Ceftiofur Hydrochloride breast injection
Preparation method is with embodiment 2.
The character of gained Ceftiofur Hydrochloride breast injection is that off-white color is to yellow oil suspension.
Carry out sedimentation granularity and Sterility testing to the said goods, it all meets the quality standard of breast injection.
Embodiment 7, Ceftiofur Hydrochloride breast injection (dry breast phase) are to effect test in the body of milch cow
1) Ceftiofur Hydrochloride breast injection (the dry breast phase) safety testing to milch cow
Healthy milk cow in lactation period primiparity and each 6 of multiparity are selected in test at random, and four Ge Ru districts respectively single give Ceftiofur Hydrochloride breast injection (dry breast phase) 1 (specification: 500mg of embodiment 2 preparation; 10ml).
1 day and (before administration) on the 0th gather each 1 time of milk sample before administration; Within after administration 12 hours, 3 days, 5,7 and 10 days, respectively adopt milk sample 1 time, sampling Shi Sigeru district all needs sampling, and discards first three milk.
Data collection: whole duration of test carries out Continuous Observation to administration milch cow, record milch cow mark, observing time, date of test and time, the often parameter such as cow head daily yielding and body temperature.Milk sample that each time point gathers detects Ruzhong somatic number (SCC), is observed the clinical symptoms such as milch cow red and swollen heat pain by palpation.
Bacteria distribution: respectively respectively gather milk sample 1 time (20mL) on the 10th after 0 day and administration before administration and carry out bacteriology checking.First breast is rinsed with clear water during sampling, with 0.1% bromo geramine or 75% ethanol, nipple and surrounding are carried out disinfection, after ethanol volatilization, manual milking, after discarding first three milk, gather milk sample in sterilizing test tubes with sterilizing test tubes, post label, low temperature (4 DEG C) is preserved and in 6h, is sent laboratory separation detection.
With multiple choices culture medium culturing bacterial isolate bacterium.Each milk sample is seeded to selective medium and is separated various pathogen.After the purified cultivation of isolated strains, identify its kind according to colonial morphology, dyeing characteristic, Biochemical Characteristics.Main SEPARATION OF GOLD Staphylococcus aureus, streptococcus (streptococcus dysgalactiae, streptococcus uberis), escherichia coli.
Result shows, at whole duration of test, in Lac Bovis seu Bubali after somatic number administration compared with before administration without significant change, after administration, bacteria distribution number reduces, and milk production of cow has no significant change, and the clinical symptoms such as red, swollen, hot, pain do not appear in the newborn district of administration.Show based on the above results, milch cow gives Ceftiofur Hydrochloride breast injection (dry breast phase) according to recommended dose single, and to milch cow without any untoward reaction, said preparation has higher safety.
2) Ceftiofur Hydrochloride breast injection (dry breast phase) is at the residue test of Lac Bovis seu Bubali
Choose 10 health to be about to enter dry cow, after milking for the last time before entering the dry breast phase, every each newborn district of cattle gives Ceftiofur Hydrochloride breast injection (dry breast phase) 1 (specification: 500mg of embodiment 2 preparation; 10ml).12h, 24h, 36h, 48h, 60h, 72h after milch cow calving gather composite sample and with going the Ultra Performance Liquid Chromatography of furanylcarbonyl ceftiofur acetamide (DCA, ceftiofur and metabolite derivatization product thereof) triple level Four bar mass spectrography (UPLC-MS/MS) of connecting to detect the concentration of DCA in milk in the milk set up.Concrete detection method: take 1mL milk in 10mL centrifuge tube with cover; Add 3mL acetonitrile, after whirling motion 1min, 10000r/min, 4 DEG C of centrifugal 10min; Get supernatant in 50ml polypropylene centrifuge tube, under 40 DEG C of water-baths, be concentrated into residue about 1mL with Nitrogen evaporator; Add 5mL DTE extracting solution, 50 DEG C of water-baths are vibrated 20 minutes, add 2mL iodoacetamide extracting solution subsequently, after abundant mixing, lucifuge leaves standstill 30 minutes, and (HLB activates through 3mL methanol in advance then to inject HLB solid phase extraction column, 3mL water balance), again with 3mL5% methanol-water washing HLB solid phase extraction column, finally use 3mL acetonitrile, collect eluent in 10mL teat glass.Eluent nitrogen under 40 DEG C of water-baths blows and is concentrated into dry, and residue 1mL acetonitrile-0.1% aqueous formic acid (5:95, V/V) redissolves, whirling motion 1min, make after residue all dissolves on centrifugal tube wall, cross 0.22 μm of filter membrane in sample introduction bottle, detect with UPLC-MS/MS liquid matter instrument.
Turn to acetyl take off furanylcarbonyl ceftiofur acetamide (DCA) by derivative to Ceftiofur Hydrochloride and metabolite thereof in residue detection test, establish Ultra Performance Liquid Chromatography tandem mass spectrum (UPLC-MS/MS) assay method of DCA in milk.Dried up by acetonitrile extraction, derivatization, Solid-Phase Extraction, nitrogen, the step such as redissolution carries out sample pre-treatments, then measure the concentration of DCA in milk with UPLC-MS/MS.Standard curve correlation coefficient (r) that this method is set up is 0.9991.Select three concentration levels to carry out interpolation recovery test, the response rate is between 82.52%-105.86%, and variation within batch coefficient is 2.95% ~ 9.82%, and interassay coefficient of variation is 6.41% ~ 7.43%.The detection of DCA in milk is limited to 0.05 μ g/L, is quantitatively limited to 0.1 μ g/L.
Result shows: Ceftiofur Hydrochloride breast injection (dry breast phase) is by recommended dose administration, after the dry breast phase terminates, can't detect ceftiofur in Lac Bovis seu Bubali and remain marker-remove furoyl ceftiofur DFC, is 100 μ g/kg lower than the MRL of ceftiofur in the milk of European Union and China's States Pharmacopoeia specifications.Therefore Ceftiofur Hydrochloride breast injection (dry breast phase) is zero day for the off-drug period of dry milk phase mammitis of cow Prevention and Curation.
3) Ceftiofur Hydrochloride breast injection (the dry breast phase) pharmacodynamics test to mammitis of cow
From 6000 Fresians of 4 test cattle farms, close on the milch cow of dry breast phase select 60, be divided into 5 groups at random, often organize 12.Be divided into 3 test medicine groups (I, II, III group), give respectively height (2), in (1), low (1/2) dosage Ceftiofur Hydrochloride breast injection (dry breast phase); 1 drug control group (IV group), gives benzathine cloxacillin injection 1; 1 non-administration blank group (V group).Above-mentioned Ceftiofur Hydrochloride breast injection is sample prepared by embodiment 2, and specification is 500mg; 10ml.
After test milch cow is milked for the last time before entering the dry breast phase, four Ge Ru district sterilization nipple perfusion administrations, after administration, massaging breasts makes medicaments uniformity distribute.The clinical condition of observed and recorded medication milch cow and breast condition; When milking for the last time before the dry breast phase respectively and milk for the first time after calving, aseptic collection milk sample carries out bacteriology checking; There are pathogenic bacterium to detect in milk sample before adding up the administration of each test group milch cow and after calving, do not detect newborn district number and the milch cow number (see table 1) of pathogenic bacterium, calculating the success rate of each group of mammitis of cow treatment of infection and prevention; Detect newborn district number and the milch cow number (see table 2) of pathogenic bacterium before adding up the administration of each test group milch cow in milk sample without pathogenic bacterium detect after calving, calculate the new infection rate of each test group milch cow pathogen.Overall merit medicine is to the treatment of dry cow breast infection and preventive effect.
Compare with calving rear udder attachment infection rate before milch cow medication tested by table 1
Note: 1) detect infectious bacteria milch cow number/detection milch cow number in head infection rate=breast, newborn district infection rate=detect infectious bacteria breast district number/detect newborn district number
Table 2 is tested milch cow calving breast infection on the 5th and is removed and new infections situation
Note: detect infectious bacteria milch cow number in 1) head clearance rate=(detect in medication fore udder in infectious bacteria milch cow number-calving rear udder attachment and detect infectious bacteria milch cow number)/medication fore udder; 2) infectious bacteria breast district number is detected before newborn district clearance rate=(detecting infectious bacteria breast district number after detecting the district's number-calving of infectious bacteria breast before medication)/medication; 3) new infeetioa cattle is do not detect breast infection bacterium before medication and detect breast infection bacterium after calving; 4) new infeetioa breast district does not detect infectious bacteria before medication and detects infectious bacteria after calving; 5) between same column numerical value, compared with blank group, tool * * subscript represents that difference extremely significantly (P<0.01).
Result of the test shows:
1) Ceftiofur Hydrochloride breast injection (dry breast phase) has good scavenging action to pathogenic bacterium in dry cow breast.Wherein the head clearance rate of high, middle dosage to infectious bacteria in cow breast reaches 83.3%-85.7%, breast district clearance rate reaches 93.3%-95.0%, the action effect of the Ceftiofur Hydrochloride breast injection (dry breast phase) of high, middle dosage is without significant difference (P > 0.05), all be better than control drug benzathine cloxacillin injection (head clearance rate 42.9%, newborn district clearance rate 50.0%); The head clearance rate of low dose group to pathogenic bacterium in cow breast also can reach 50.0%, and newborn district clearance rate can reach 61.5%, and action effect is suitable with control drug.
2) dry cow perfusion Ceftiofur Hydrochloride breast injection (dry breast phase) and benzathine cloxacillin injection control drug all obviously can reduce the infection rate of various pathogenic bacterium in cow breast.With the prevention of benzathine cloxacillin injection compared with therapeutic effect, the Ceftiofur Hydrochloride breast injection (dry breast phase) of high, middle dosage is more remarkable to the improvement result of dry cow head infection rate and newborn district infection rate; Low dosage Ceftiofur Hydrochloride breast injection is suitable with control drug with the improvement of newborn district infection rate to the head infection rate of dry breast phase mastitis; Blank group milch cow does the head infection rate of newborn after date mastitis and newborn district and infects and slightly rise.
3) dry cow uses Ceftiofur Hydrochloride breast injection (dry breast phase) obviously can reduce the new infections rate of various antibacterial in breast.Dry cow perfusion Ceftiofur Hydrochloride breast injection (dry breast phase) and control drug benzathine cloxacillin injection all have scavenging action to pathogenic bacterium various in cow breast and prevent to suffer from puerperal the effect of mastitis.Wherein the Ceftiofur Hydrochloride breast injection (dry breast phase) of high, the middle dosage action effect of suffering from mastitis puerperal to streptococcus uberis, streptococcus dysgalactiae, S. aureus L-forms and colibacillary scavenging action in breast and prevention is better; The Ceftiofur Hydrochloride breast injection of control drug and low dosage (dry breast phase) suffers from mastitis to the scavenging action of mastitis pathogenic bacterium and prevention puerperal also has certain curative effect.
4) milch cow dry breast phase perfusion Ceftiofur Hydrochloride breast injection (dry breast phase), has mastitis pathogenic bacterium streptococcus, S. aureus L-forms, escherichia coli etc. and well controls scavenging action.High (2), in the Ceftiofur Hydrochloride breast injection (dry breast phase) of (1) dosage to the treatment of pathogenic bacterium in dry cow breast and preventive effect there was no significant difference, therefore advise that the dosage of Clinical practice Ceftiofur Hydrochloride breast injection (dry breast phase) treatment and prevention mammitis of cow is: when milch cow enters the dry milk phase, each newborn district gives 1 Ceftiofur Hydrochloride breast injection (dry breast phase) (specification: 500mg; 10ml).
Carry out identical test according to the method for effect test in the body of embodiment 7 to the product of embodiment 1,3-6, the effect of its result and embodiment 2 is suitable.Show Ceftiofur Hydrochloride breast injection provided by the invention (dry breast phase) safety, noresidue, little, evident in efficacy to local tissue stimulation to there is high promotional value.
Claims (10)
1. a Ceftiofur Hydrochloride breast injection, is made up of following supplementary material: Ceftiofur Hydrochloride 2.5-10g, glyceryl monostearate 0.5-5g, suspending agent 0.5-5g, vegetable oil add to 100ml.
2. breast injection according to claim 1, is characterized in that: described Ceftiofur Hydrochloride breast injection is made up of following supplementary material: Ceftiofur Hydrochloride 5g, glyceryl monostearate 0.5-5g, suspending agent 0.5-5g, vegetable oil add to 100ml.
3. breast injection according to claim 1 and 2, is characterized in that: described vegetable oil is selected from following at least one: soybean oil, Oleum Camelliae, Semen Maydis oil, Oleum Arachidis hypogaeae semen and Oleum Gossypii semen; Be preferably soybean oil.
4. the breast injection according to any one of claim 1-3, is characterized in that: described suspending agent is selected from following at least one: Tween 80, sorbester p17 and soybean phospholipid; Be preferably sorbester p17.
5. the breast injection according to any one of claim 1-4, is characterized in that: the particle diameter of described Ceftiofur Hydrochloride is 5-10 μm.
6. the breast injection according to any one of claim 1-5, is characterized in that: described Ceftiofur Hydrochloride breast injection is used for milch cow and does preventing and/or treating of breast phase mastitis.
7. prepare a method for arbitrary described Ceftiofur Hydrochloride breast injection in claim 1-6, comprise the steps:
1) by after appropriate described vegetable oil and the mixing of described glyceryl monostearate, heat fused, obtains mixed system;
2) in described mixed system, add described suspending agent, described Ceftiofur Hydrochloride, then add vegetable oil to full dose, grinding evenly, obtains described Ceftiofur Hydrochloride breast injection.
8. method according to claim 7, is characterized in that: the condition heated described in step 1) is: heat 15 ~ 30 minutes for 60 ~ 80 DEG C; Step 2) described in grind and carry out in colloid mill; The consumption of vegetable oil described in step 1) is the 40%-60% of vegetable oil total amount.
9. the method according to claim 7 or 8, is characterized in that: described vegetable oil also needs the pretreatment through filtration and heat sterilization before use; The condition of described heat sterilization is: 150-160 DEG C of sterilizing 2-3 hour.
10. the Ceftiofur Hydrochloride breast injection according to any one of claim 1-5 preparation prevent and/or treat milch cow do breast phase mastitis medicine in application.
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| CN109394679A (en) * | 2018-12-07 | 2019-03-01 | 中国农业科学院饲料研究所 | A kind of Rifaximin ointment for animal hoof disease |
| CN110063991A (en) * | 2019-05-19 | 2019-07-30 | 浙江海正动物保健品有限公司 | Compound Ceftiofur Hydrochloride breast injection |
| CN112924633A (en) * | 2021-05-10 | 2021-06-08 | 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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| CN109394679A (en) * | 2018-12-07 | 2019-03-01 | 中国农业科学院饲料研究所 | A kind of Rifaximin ointment for animal hoof disease |
| 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 |
| CN110063991A (en) * | 2019-05-19 | 2019-07-30 | 浙江海正动物保健品有限公司 | Compound Ceftiofur Hydrochloride breast injection |
| CN112924633A (en) * | 2021-05-10 | 2021-06-08 | 天津瑞普生物技术股份有限公司 | Sterility detection method for ceftiofur oil suspension 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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