CN103083336A - Synergistic sulfamethoxypyridazine injection for livestock - Google Patents
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Abstract
The invention relates to a compound sulfamethoxypyridazine injection and a preparation method thereof. The synergistic sulfamethoxypyridazine injection has enduring drug effect and obvious curative effect. The injection comprises the following components in parts by weight: 10-20 parts of sulfamethoxypyridazine, 2-4 parts of indometacin, 2-4 parts of trimethoprim, 5-10 parts of polyethyleneglycol 8000, 30-40 parts of propanediol, 0.1-0.2 part of antioxidant, 30-55 parts of water for injection, and sufficient amount of pH regulator for regulating the pH value of the system to 9.5-10.5. The preparation method comprises the following steps: adding the antioxidant into the water for injection to prepare a solution A, adding the polyethyleneglycol 8000, sulfamethoxypyridazine, indometacin and trimethoprim into the propanediol, and completely dissolving by stirring to prepare a solution B; and merging, filtering, packaging and sterilizing to obtain the finished product. The injection provided by the invention is a new drug preparation with triple effects, and has the advantages of long drug effect, low consumption, low application frequency, small irritation, quick drug effect taking and wide curative range.
Description
Technical field
The present invention relates to a kind of veterinary drug, be specifically related to animal compound sulfamethoxypyridazine injection and preparation method thereof.
Background technology
The sulfa drugs clinical practice has the history of decades, sulfamethoxypyridazine (Sulfamethoxypyridazine, write a Chinese character in simplified form SMP) be one of principal item of sulfa drugs, effective to most of gram positive bacterias and part gram negative bacteria, particularly the sensitive organisms such as streptococcus, Fructus Vitis viniferae ball, streptococcus pneumoniae, escherichia coli, Listeria monocytogenes infect, chlamydia and some protozoon are also effective, belong to broad-spectrum antibacterial agent.Hold time Babalus bubalis L. 24 hours of effective blood drug concentration, pig 5.8 hours, goat 7 hours, sheep 2 hours.This product is applicable to the systemic infection due to various animal sensitive organisms, and determined curative effect, stable in properties, easy to use, low price are convenient to again long preservation.To be used for the treatment of the choice drug that the brain antibacterial infects in sulphonamides.Share with suitable dynamical Trimethoprim, more can make the clinical practice of sulfamethoxypyridazine that new wide future is arranged.
Trimethoprim (Trimethoprim, have another name called TMP) be artificial synthetic antibacterial drug, can strengthen the effect of sulfonamides, antimicrobial spectrum is similar and active to sulfonamides stronger, multiple gram positive bacteria and negative bacterium are all had antibacterial action, and its mechanism of action is to suppress dihydrofolate reductase, makes dihydrofoilic acid can not be reduced into tetrahydrofolic acid, thereby hinder sensitive organism folic acid metabolism and utilization, thereby overslaugh thalline nucleic acid is synthetic.When this class medicine and sulfonamides share, but double blocking folic acid metabolism effect, make antibacterial action strengthen several times to nearly a hundred times, even make bacteriostasis become bactericidal action, and can reduce the generation of Resistant strain, TMP mainly discharges from urine, discharges 40%～60% of total amount in 24 hours, also can be from excrement, milk, bile excretion.
In prior art, " Chinese veterinary pharmacopoeia " version, " Chinese veterinary drug standard " version in 1978 in 2010 recorded raw material: sulfamethoxypyridazine, trimethoprim; Preparation: compound sulfonamide methoxy pyridazine injection.The compound sulfonamide methoxy pyridazine injection of veterinary drug allusion quotation is comprised of sulfamethoxypyridazine and trimethoprim, and antibacterial is infected certain control effect.But antibacterial, protozoan infection now is the height Combination more.As high heat due to Eperythrozoon, toxoplasma, chlamydia and with streptococcus, immunosuppressant virus mixed infection.These diseases infect clinical manifestation infectiousness, Gao Re and inflammation, and are undesirable with the compound sulfonamide methoxy pyridazine injection for treating effect that pharmacopeia is recorded, injection in common a day 2 times, and zest is strong and dosage is large.Its main cause may be mainly that the blood time of staying of sulfamethoxypyridazine itself is shorter, causes drug effect short, and consumption is large.
Summary of the invention
The invention provides a kind of veterinary synergic sulfamethoxypyridazine injection and preparation method thereof, this compound sulfamethoxazole methoxy pyridazine injection lasting medicine, evident in efficacy.
The technical scheme that the present invention takes is: a kind of veterinary synergic sulfamethoxypyridazine injection is characterized in that: comprise following weight portion:
PH adjusting agent, consumption are enough to the regulation system pH value between 9.5-10.5.
Preferably, described antioxidant is sodium thiosulfate or sodium sulfite.This is the preferred embodiment of empirical tests.Certainly, other antioxidants that are suitable for component compatibility of the present invention also are fine.
Preferably, described pH adjusting agent is sodium hydroxide solution or hydrochloric acid, is used for regulating the pH value of injection of the present invention between 9.5-10.5.During actual preparation, according to circumstances regulate, pH value is high to go beyond the scope, and available hydrochloric acid is regulated, and pH value is lower than this scope, and the available hydrogen sodium hydroxide solution is regulated.For the ease of controlling the addition of pH adjusting agent, sodium hydroxide or hydrochloric acid normally drip with the form of solution.
Preferably, in described injection:
Preferably, in described injection:
Certainly, the usage and dosage of pH adjusting agent still is as the criterion with the pH value of system, not concrete the restriction.
The preparation method of veterinary synergic sulfamethoxypyridazine injection of the present invention comprises the steps:
1): get water for injection and be heated to 50-60 ℃, add antioxidant, stir and make its whole dissolvings, regulate pH value to 9-11 with pH adjusting agent, be prepared into A liquid, standby;
2): got propylene glycol and be heated to 60-70 ℃, added PEG 8000, sulfamethoxypyridazine, indomethacin, trimethoprim, stirred and make its whole dissolvings, be prepared into B liquid;
3): above-mentioned A liquid is added in B liquid stir, continue to stir 30 minutes, medicinal liquid is clear and bright adjusts pH value between 9.5-10.5 afterwards with pH adjusting agent, obtains filtrate after organic membrane filtration;
4): with above-mentioned filtrate with filling and sealing machine respectively fill in bottle, through 115 ℃, pressure 0.2MPa sterilization 30 minutes, can obtain faint yellow compound sulfamethoxazole methoxy pyridazine injection to yellow clear liquid.
During fill, can fill in cillin bottle, ampoule bottle, vial, loading amount comprises 5ml, 10ml etc.First can avoid soda acid to depart from product requirement with the pH adjusting agent adjustment during preparation too large, cause substance reaction or variation.
The invention has the advantages that above-mentioned injection can provide effective treatment for secondary infection and the mixed infection of the diseases such as streptococcicosis, toxoplasmosis, eperythrozoonosis, colibacillosis, asthma.And have following remarkable advantage:
1. the experiment of above-mentioned injection shows: its in vivo valid density hold time for 71.11h ± 9.40h, and common compound sulfonamide methoxy pyridazine injection is only 47.99h ± 10.21h, long-acting successful is better than common compound sulfonamide methoxy pyridazine injection, therefore can think that but this injection 3-4 days medication once, has significantly reduced dosage.
2. when sulfamethoxypyridazine and traditional trimethoprim potentiation compatibility, infect effective in cure to solving common protozoon or antibacterial, only pathogenic microorganism is had inhibitory action at clinical treatment antibacterial, protozoon height mixed infection, do not have killing action, antibacterial easily produces drug resistance.All medicines are united use after our compatibility indomethacin, PEG 8000, and drug effect strengthens several times to tens times, present antibacterial is produced killing action, also are difficult for producing drug resistance.
3. the indomethacin major function is antiinflammatory, analgesic and analgesia, usually disease is in generating process,, hyperpyrexia depressed with spirit, inflammatory pain etc., the present invention has specially good effect to this type of symptom, usually have the multiple effects such as anti-inflammation, antipyretic-antalgic, have simultaneously symptomatic treatment and etiological treatment for disease.
4. the present invention is the new medicinal preparation of triple effect unification, and use amount is little, the medication number of times is few, zest is little, the drug effect performance is fast, have the characteristics for the treatment of both the principal and secondary aspects of a disease.
5. this injection with the several drugs use that is mixed, has been saved production cost, has improved added value of product.The toxic and side effects that has occurred due to the medicine mismate when having reduced simultaneously treatment.
Theoretical foundation of the present invention may be: better brought into play the effect of indomethacin and PEG 8000.Indomethacin (Indomethacin) indomethacin has obvious potent effect to some antibiotic or antimicrobial drug.Different from the mechanism of action of trimethoprim, mainly because lung tissue is tissue basophil, when pulmonary is inflamed, the sulfa drugs of some antibiotic of indomethacin portability such as high dose preferentially arrives infection site, and high concentration is gathered in around inflammatory, indomethacin can make sulfa drugs concentration in infected tissue improve 4-8 doubly, and after coupling, the anti-infectives use amount can reduce by half and even can only be 1/4 of positive usual amounts.Indomethacin also has significant antiinflammatory, analgesic and analgesic activity.Its antiinflammation is powerhouse in anti-inflammation drugs.It is to the high febrile illness antipyretic and anti-inflammatory of pig, the chicken colibacillosis thoracic cavity infection, and infectious serositis in duck and poultry pneumonia, hydrothorax and Combination pneumonia have significant adjuvant treatment effect, and this may have obviously potent relevant with antiinflammation with indomethacin.
Polyethylene Glycol has another name called α-hydrogen-ω-hydroxyl (oxygen-1,2-second two bases) polymer, PEG 8000 is that molecular weight is the polymer of 7500-8500, it is the flexible macromolecule compound, sulfanilamide sulfamethoxypyridazine, trimethoprim, indomethacin can be adsorbed on macromolecular chain with drug regimen, increase liquid medicine stability; Contact the biofilm structure that can change various types of cells with bacterial body, make the lipid molecule of two cells contacting point place plasma membranes occur to evacuate and restructuring, increase antibacterial effect.Polymer substance can also improve the denseness of injection, the prolong drug time of staying in animal body, forms class controlled release process, thereby is conducive to drug absorption and extends drug effect.
The specific embodiment
One, the preferred embodiments of the present invention
Embodiment 1
1, formula
Sulfamethoxypyridazine: 10g, trimethoprim: 2g, indomethacin: 2g, sodium thiosulfate: 0.1g, PEG 8000: 5g, propylene glycol 30ml, 10ml concentration is that sodium hydroxide solution and each portion of 0.5mol/L hydrochloric acid of 1mol/L is standby, water for injection 55ml.
2: preparation method
The first step is got water for injection and is heated to 50-60 ℃, adds respectively sodium thiosulfate, PEG 8000, stirs to make its whole dissolvings, regulates pH value in 10 left and right with sodium hydroxide solution, is prepared into A liquid standby;
Second step is got propylene glycol, is heated to 60-70 ℃, adds respectively sulfamethoxypyridazine, trimethoprim, indomethacin, stirs and makes its whole dissolvings, is prepared into B liquid;
The 3rd step added A liquid in B liquid to stir, and continued to stir 30 minutes, and the adjusting pH value is 9.5-10.5; Be first 0.45 micron organic membrane filtration with diameter, then be 0.22 micron organic membrane filtration with diameter, obtain filtrate;
The 4th step, use the filling and sealing machine fill in bottle above-mentioned filtrate, through 115 ℃, pressure 0.2MPa sterilized 30 minutes, can obtain the compound sulfonamide methoxy pyridazine injection of faint yellow or yellow clear liquid.
Embodiment 2
1, formula
Sulfamethoxypyridazine: 15g, trimethoprim: 3g, indomethacin: 3g, sodium thiosulfate: 0.15g, PEG 8000: 7.5g, propylene glycol 35ml, 10ml concentration is that sodium hydroxide solution and each portion of 0.5mol/L hydrochloric acid of 1mol/L is standby, water for injection 50ml.
2: preparation method
The first step is got water for injection and is heated to 50-60 ℃, adds respectively sodium thiosulfate, PEG 8000, stirs to make its whole dissolvings, regulates pH value in 10 left and right with sodium hydroxide solution, is prepared into A liquid standby;
Second step is got propylene glycol, is heated to 60-70 ℃, adds respectively sulfamethoxypyridazine, trimethoprim, indomethacin, stirs and makes its whole dissolvings, is prepared into B liquid;
The 3rd step added A liquid in B liquid to stir, and continued to stir 30 minutes, and the adjusting pH value is 9.5-10.5.Be first 0.45 micron organic membrane filtration with diameter, then be 0.22 micron organic membrane filtration with diameter, obtain filtrate;
The 4th step, use the filling and sealing machine fill in bottle above-mentioned filtrate, through 115 ℃, pressure 0.2MPa sterilized 30 minutes, can obtain the compound sulfonamide methoxy pyridazine injection of faint yellow or yellow clear liquid.
Embodiment 3
1, formula
Sulfamethoxypyridazine: 15g, trimethoprim: 3g, indomethacin: 3g, sodium sulfite: 0.15g, PEG 8000: 7.5g, propylene glycol 30ml, 10ml concentration is that sodium hydroxide solution and each portion of 0.5mol/L hydrochloric acid of 1mol/L is standby, water for injection 55ml.
2: preparation method
The first step is got water for injection and is heated to 50-60 ℃, adds respectively sodium sulfite, PEG 8000, stirs to make its whole dissolvings, regulates pH value 9.5, is prepared into A liquid standby;
Second step is got propylene glycol, is heated to 60-70 ℃, adds respectively sulfamethoxypyridazine, trimethoprim, indomethacin, stirs and makes its whole dissolvings, is prepared into B liquid;
The 3rd step added A liquid in B liquid to stir, and continued to stir 30 minutes, and the adjusting pH value is 9.5-10.5.Be first 0.45 micron organic membrane filtration with diameter, then be 0.22 micron organic membrane filtration with diameter, obtain filtrate;
The 4th step, use the filling and sealing machine fill in bottle above-mentioned filtrate, through 115 ℃, pressure 0.2MPa sterilized 30 minutes, can obtain the compound sulfonamide methoxy pyridazine injection of faint yellow or yellow clear liquid.
Embodiment 4
1, formula
Sulfamethoxypyridazine: 20g, trimethoprim: 4g, indomethacin: 4g, sodium thiosulfate: 0.2g, PEG 8000: 10g, propylene glycol 40ml, 10ml concentration is that sodium hydroxide solution and each portion of 0.5mol/L hydrochloric acid of 1mol/L is standby, water for injection 40ml.
2: preparation method
The first step is got water for injection and is heated to 50-60 ℃, adds respectively sodium thiosulfate, PEG 8000, stirs to make its whole dissolvings, regulates pH value 10, is prepared into A liquid standby;
Second step is got propylene glycol, is heated to 60-70 ℃, adds respectively sulfamethoxypyridazine, trimethoprim, indomethacin, stirs and makes its whole dissolvings, is prepared into B liquid;
The 3rd step added A liquid in B liquid to stir, and continued to stir 30 minutes, and the adjusting pH value is 9.5-10.5.Be first 0.45 micron organic membrane filtration with diameter, then be 0.22 micron organic membrane filtration with diameter, obtain filtrate;
The 4th step, use the filling and sealing machine fill in bottle above-mentioned filtrate, through 115 ℃, pressure 0.2MPa sterilized 30 minutes, can obtain the compound sulfonamide methoxy pyridazine injection of faint yellow or yellow clear liquid.
Embodiment 5
1, formula
Sulfamethoxypyridazine: 20g, trimethoprim: 4g, indomethacin: 4g, sodium sulfite: 0.2g, PEG 8000: 10g, propylene glycol 30ml, 10ml concentration is that sodium hydroxide solution and each portion of 0.5mol/L hydrochloric acid of 1mol/L is standby, water for injection 50ml.
2: preparation method
The first step is got water for injection and is heated to 50-60 ℃, adds respectively sodium sulfite, PEG 8000, stirs to make its whole dissolvings, regulates pH value 10, is prepared into A liquid standby;
Second step is got propylene glycol, is heated to 60-70 ℃, adds respectively sulfamethoxypyridazine, trimethoprim, indomethacin, stirs and makes its whole dissolvings, is prepared into B liquid;
The 3rd step added A liquid in B liquid to stir, and continued to stir 30 minutes, and the adjusting pH value is 9.5-10.5.Be first 0.45 micron organic membrane filtration with diameter, then be 0.22 micron organic membrane filtration with diameter, obtain filtrate;
The 4th step, use the filling and sealing machine fill in bottle above-mentioned filtrate, through 115 ℃, pressure 0.2MPa sterilized 30 minutes, can obtain the compound sulfonamide methoxy pyridazine injection of faint yellow or yellow clear liquid.
Two, the pharmacokinetics research of compound sulfamethoxazole methoxy pyridazine injection in the pig body
1, materials and methods
1.1 medicine
Compound sulfamethoxazole methoxy pyridazine injection A1: adopt the present invention's preparation of embodiment 2 preparations.
Compound sulfonamide methoxy pyridazine injection A2: Chongqing animal pharmaceutical factory produces.
The sulfamethoxypyridazine standard substance: be 99.3% without water content, lot number is 1110027, is provided by China Veterinery Drug Inspection Office.
The sulfamethoxypyridazine crude drug: be 98.2% without water content, lot number is 111107, and Huangyan, Zhejiang animal pharmaceutical factory produces.
1.2 test solution method
The HPLC method.Mobile phase: glacial acetic acid-acetonitrile-methanol solution.
1.3 experimental animal
24 of health pig, body weight 30.25kg ± 4.15kg is available from Yunmen kind pig farm, Hechuan, Chongqing.
1.4 administration and blood specimen collection
24 pigs are divided into 2 groups at random, use the A1 injection for the 1st group, inject with the A2 injection, carry out intramuscular injection by 0.3mL/kg dosage respectively for the 2nd group.
Adopt the primary blank blood sample before administration, after administration respectively at the 0.25th, 0.50,0.75,1.00,2.00,3.00,5.00,9.00,12.00,24.00,36.00,48.00,72.00,96.00,108.00,120.00h is from the vena cava anterior 5mL that takes a blood sample, be placed in heparin centrifuge tube mixing, the centrifugal 8min of 3500r/min, separated plasma carries out HPLC and measures.
1.5 date processing
Adopt " MCPKP " pharmacokinetics calculation procedure that data are processed.
Result shows: the elimination half-life of A1 injection and A2 injection, (t1/2 β) was respectively 19.74h ± 4.52h and 9.27h ± 1.56h; The time (tmax) be respectively 1.23h ± 0.19h and 2.23h ± 0.32h; Peak concentration (Cmax) is respectively 21.20 μ g/mL ± 2.11 μ g/mL and 15.89 μ g/mL ± 2.40 μ g/mL;
Area under curve (AUC) is respectively 529.32 μ g/ (mLh) ± 28.22 μ g/ (mLh) and 192.25 μ g/ (mLh) ± 10.89 μ g/ (mLh); The valid density tcp (ther) that holds time is respectively 71.11h ± 9.40h and 47.99h ± 10.21h, and in blood, minimum active drug concentration is 0.5 μ g/mL.
2, discuss
This result of the test shows, the compound sulfamethoxazole methoxy pyridazine injection that adopts the present invention's preparation with the 0.3mL/kg intramuscular injection after, the elimination half-life is 19.74h ± 4.52h, significantly is longer than normal injection agent 9.27h ± 1.56h.
The pharmacokinetics analysis result shows, compound sulfamethoxazole methoxy pyridazine injection and the pharmacokinetics of compound sulfonamide methoxy pyridazine injection in the pig body meet two-compartment model.When eliminating half-life, peak, peak concentration, area under curve and valid density are held time etc. on parameter, and there were significant differences (P＜0.05).
The blood drug level testing result shows, the valid density of compound sulfamethoxazole methoxy pyridazine injection of the present invention is held time for 71.11h ± 9.40h, and compound sulfonamide methoxy pyridazine injection is only 47.99h ± 10.21h; The former half-life is 2 times of the latter.This explanation compound sulfamethoxazole methoxy pyridazine injection of the present invention is eliminated slow than common compound sulfonamide methoxy pyridazine injection, the time of keeping in vivo blood drug level is long, and long-acting successful is better than common compound sulfonamide methoxy pyridazine injection.
Three, the extracorporeal bacteria inhibitor test of the compound sulfamethoxazole methoxy pyridazine injection of the present invention's preparation
Compound sulfamethoxazole methoxy pyridazine injection B1, the product of the homemade embodiment 3 of laboratory;
Compound sulfonamide methoxy pyridazine injection B2: Chongqing animal pharmaceutical factory produces;
Escherichia coli (standard), Salmonella (standard), staphylococcus aureus (standard) are purchased from China Veterinary Drugs Supervisory Inst..
1, method: picking escherichia coli (standard), Salmonella (standard), staphylococcus aureus (standard) culture, streak inoculation is on agar plate, circular rustless steel tubule (internal diameter 6nm with sterilization, external diameter 8nm, high 10nm) be positioned on flat board, pressurization gently, make itself and the dull and stereotyped tight that contacts, 6 steel pipes of each dull and stereotyped placement, drip in the steel pipe for reagent liquid respectively: with B1 liquid and B2 liquid respectively water for injection be diluted to 20mg/ml (sulfamethoxypyridazine), 10mg/ml (sulfamethoxypyridazine), 5mg/ml (sulfamethoxypyridazine).To add for the flat board after reagent liquid and cultivate 10-20 hour at 37 ℃, measure inhibition zone size and statistical result.
2, result: see Table 1.As can be seen from Table 1, compound sulfamethoxazole methoxy pyridazine injection of the present invention is significantly higher than compound sulfonamide methoxy pyridazine injection.
Table 1: In Vitro Bacteriostasis experimental result
Four, compound sulfamethoxazole methoxy pyridazine injection is at the veterinary clinic effect
1. materials and methods
1.1 medicine
Compound sulfamethoxazole methoxy pyridazine injection, the sample of the employing embodiment of the present invention 2.
1.2 case source: the technical staff in the Hechuan, the areas such as Wusheng, Yuechi gather clinical natural occurrence case, are respectively pig streptococcicosis 337 examples, porcine nameless high-fever 142 examples, infectious serositis in duck 3250 examples, rabbit coccidiosis 284 examples, sick 235 examples of yellow and white dysentery of piglet, chicken whitecomb 2780 examples, baby swine paratyphoid 332 examples, Mammitis of cattle 101 examples.
1.3 case diagnosis: with natural cases according to epidemiology, clinical symptoms, pathological change, Laboratory Diagnosed.Analysis-by-synthesis is made a definite diagnosis.
1.4 implementation process: carry out case by the technical staff of this seminar by test requirements document and select and implement treatment, and log.
1.5 result is judged
With natural cases according to dosage with the administration course for the treatment of, observe in the week, pay a return visit and record the state of an illness.The case criterion:
Cure: 3-4 future trouble poultry disease of medication disappears fully, and spirit, body temperature, appetite recover normal, and urine feces is normal.
Effectively: 3-4 future trouble poultry disease of medication disappears substantially, and spirit, body temperature, appetite make moderate progress, and urine feces is normal.
Invalid: 4 future troubles of medication poultry diseases do not disappear, and sb.'s illness took a turn for the worse or dead, and urine stool colour, character are undesired.
2. result: see Table 2.Compound sulfamethoxazole methoxy pyridazine injection has good therapeutic effect as can be seen from Table 2, the effective percentage such as pig streptococcicosis, porcine nameless high-fever, infectious serositis in duck, rabbit coccidiosis, yellow and white dysentery of piglet disease, chicken whitecomb, baby swine paratyphoid, Mammitis of cattle are reached more than 96.0%, cure rate is all more than 91%, and infectious serositis in duck, chicken whitecomb are had specially good effect.
Table 2: compound sulfamethoxazole methoxy pyridazine injection clinical therapeutic efficacy statistical table
Claims (5)
1. veterinary synergic sulfamethoxypyridazine injection is characterized in that: comprise following weight portion:
PH adjusting agent, consumption are enough to the regulation system pH value between 9.5-10.5.
2. a kind of veterinary synergic sulfamethoxypyridazine injection according to claim 1, it is characterized in that: described antioxidant is sodium thiosulfate or sodium sulfite.
3. a kind of veterinary synergic sulfamethoxypyridazine injection according to claim 1, it is characterized in that: described pH adjusting agent is sodium hydroxide solution or hydrochloric acid.
4. according to claim 1 and 2 or 3 described a kind of veterinary synergic sulfamethoxypyridazine injection is characterized in that: in described injection:
5. a kind of veterinary synergic sulfamethoxypyridazine injection according to claim 4 is characterized in that: in described injection:
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| CN101773474A (en) * | 2010-02-26 | 2010-07-14 | 湖北龙翔药业有限公司 | Preparation method of toltrazuril soluble powder |
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| CN113304158A (en) * | 2021-06-10 | 2021-08-27 | 山东省农业科学院畜牧兽医研究所 | Application of sulfamethoxypyrazine in preparation of product for preventing and/or treating bovine parainfluenza virus |
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Application publication date: 20130508 |