CN101002947B - Target medicine used for treating bacteriosis, and its preparing method - Google Patents
Target medicine used for treating bacteriosis, and its preparing method Download PDFInfo
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- CN101002947B CN101002947B CN2007100342672A CN200710034267A CN101002947B CN 101002947 B CN101002947 B CN 101002947B CN 2007100342672 A CN2007100342672 A CN 2007100342672A CN 200710034267 A CN200710034267 A CN 200710034267A CN 101002947 B CN101002947 B CN 101002947B
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Abstract
A target medicine for treating bacterial disease features that its active component is a conjugate of the antibacterial serum antibody and antibiotic, and the target medicine can move toward bacteria, resulting in high effect. Its preparing process is also disclosed.
Description
Technical field
The present invention relates to a kind of targeted drug that is used for treating bacteriosis and preparation method thereof.
Background technology
At present, conventional antibiotic when the treatment bacterial disease, no matter through which kind of administration, equal (except that minority positions such as brain) uniform distribution in animal body tissue and body fluid after medicine enters in the animal body, drug concentrations is called blood drug level.Along with the metabolism of liver to medicine, blood drug level is more and more lower.And antibacterial is not equally distributed in animal body, mainly is distributed in its target organ.Even in target organ, medicine also relies on random collision fully with combining of antibacterial, therefore, in order to guarantee curative effect, must be in the tissue of antibacterial place the long period keep higher drug level.Therefore, when using the antibiotic therapy bacterial disease, must a large amount of administrations in certain course of treatment, be not less than desired blood drug level with the drug level of keeping in the body tissue.So just bring a lot of sequela.1) long-term a large amount of medication, medicine especially deposits in the fatty tissue at body tissue, forms drug residue, threatens human health.2) a large amount of medicines are not only caused a large amount of wastes by metabolism, and in drug metabolism processes, also can the metabolism organ of medicine be caused damage; Epidemic prevention and control cost and cost are too high.3) how many medicines that enters in the bacterial cell differs, the free variation that produces at this medicine of the antibacterial that makes (entering cell dose antibacterial seldom), thus form Resistant strain.
In recent years, the antibody drug research and development of treatment tumor have obtained breakthrough progress, become the focus in biotech drug field.Be at present clinical before, in all kinds of biotech drugs of clinical I phase and clinical II phase, the kind number of bits of antibody drug is occupied the forefront.Antibody drug has two kinds of functions, and the one, combine with the target molecule specificity, the 2nd, killing tumor cell, its effect mainly is to realize by the cytotoxicity that relies on complement and the cell-mediated two kinds of immunologic mechanisms of cytotoxicity of antibody.In order to strengthen the tumor cell killing activity of antibody drug, amycin, daunorubicin, bleomycin, neocarzinostain NCS, mitomycin, Bleomycin A5, B1eomycin, card Ritchie mycin, Lidamycin LDM and geldanamycin etc. all once with antibody coupling, be used to prepare the anti-tumour antibody medicine.
Current, the research direction of exploitation treatment tumor and cancer has following four aspects:
1) antibody and the medicine commissure thing of development miniaturization: its reason is: antibody and conjugate thereof are macromolecular substances (with IgG type antibody are example, its molecular weight is about 150kDa, the molecular weight that is connected the chemo-immunity conjugate made from medicine is bigger), huge antibody drug molecule is difficult to arrive by capillary endothelial layer and ECS the tumor cell in solid tumor deep, thereby development miniaturization antibody drug is significant to improving curative effect; Reach the purpose of antibody miniaturization, general now development monoclonal antibody.In addition, utilize single-chain antibody or single domain antibody to prepare antibody drug and can further reduce its molecular weight, reaching new level aspect the antibody drug molecule miniaturization.
2) seek the medicine that tumor cell is had strong lethality: owing to inject the limited amount of the actual arrival of intravital antibody drug tumor cell, for obtaining good result, antibody drug needs high efficiency, realizes only having trace to arrive target site and gets final product killing tumor cell.
3) development chimeric antibody and humanized antibody: what early studies in man was used is the monoclonal antibody (monoclonal antibody of rat, hamster, mice) in rodent source, owing to itself be exactly heterologous protein, have immunogenicity, so, in human body, will soon produce human antimouse antibody.Host response can change the characteristics of pharmacokinetics of antibody drug significantly, monoclonal antibody medicine is removed rapidly, and be difficult to rechallenge.Though many hematologic malignancies patient immune system defectiveness, the human antimouse antibody reaction still can have a strong impact on the curative effect of monoclonal antibody medicine.The low immunogenicity monoclonal antibody of research and development, the technology of improving people's antibody response are that monoclonal antibody medicine really enters clinical key.These technology comprise chimera technology, humanization technology, Primates source technology and transgenic technology, people's antibody of promptly producing from transgenic mice or phage.Chimeric antibody is the antibody that variable region (variable domains) comprises other source antigen binding site, and the constant region of protein chain (constant domains) is the people source.Humanized antibody improves to some extent than chimeric antibody again.Humanized antibody is real chimeric antibody, and it has only the variable region part of heavy chain and light chain to comprise that a few amino acids is to be derived from immune animal in complement determining area (CDR) and the framework.The antibody remainder still is the people source.
4) modified antibodies makes it to tumor cell suitable affinity be arranged: antibody has determined the effectiveness and the economy of the clinical consumption of antibody drug to the affinity of target cell.Tradition monoclonal antibody dosage is very low to be limit by its nonspecific toxic reaction, and high-affinity antibody can increase cell toxicity medicament to the tumor tissues targeting.Yet affinity of antibody is too high, may influence the permeability of medicine to tumor on the contrary because lot of antibodies is gathered in the periphery of tumor tissues.
From pertinent literature and the research tendency of having published, the sole purpose of antibody and medicine commissure is treated tumor and cancer exactly both at home and abroad at present, and at the improved properties and the modified antibodies of tumor cell and select medicine.And how medicine is connected with antibody, and all research institutions all keep secret, as own technology, and becomes the wuwa of the new drug quality competition that different research institutions produce.
And the direction and the trend of the sick new drug research of directed toward bacteria are at present:
In recent years both at home and abroad mainly concentrate on the analyzing and testing of genetic breeding and biosynthesis, separation of antibiotics purification and product structure modification, antibiotic product of screening, antibiotics generated bacterium of antibiotics and quality monitoring, antibiotic pharmacology and clinical and farming animals with six aspects such as antibiotic at antibiotic research.
From the antibiotics research document of having published, can know, antibiotic research mainly be concentrated on seek the existing antibiotic of new antibacterial and Fungicidal substance, modification and improvement at present with the opposing drug resistance and to three broad aspect such as existing antibiotic raising output and uses rationally.To how improving existing antibiotic antibacterial and germicidal efficiency, how effectively to eliminate antibacterial to having antibiotic drug resistance without any substantial progress, and can expect that available research achievements only can be brought the consequence of " as virtue rises one foot, vice rises ten " at present.
Summary of the invention
Purpose of the present invention aims to provide a kind of can dividing a word with a hyphen at the end of a line to the antibacterial orientation, accelerated the speed that medicine enters bacterial cell greatly, total dosage is few, and drug effect rapidly and efficient, short treating period helps reducing the targeted drug that is used for treating bacteriosis of animal body Chinese medicine residual quantity.
Another purpose of the present invention aims to provide the above-mentioned preparation method that is used for the targeted drug of bacterize.
Targeted drug of the present invention, active component are the conjugate that antibacterium serum antibody and the crosslinked structure of antibiotic form.
Pass through the stable conjugate of Polyethylene Glycol (PEG) be combined between antibacterium serum antibody and the antibiotic.The preferred PEG6000 of described PEG.
Described antibacterium serum antibody can be the serum antibody for preparing behind the inactivated vaccine immunizing rabbit of pathogen preparation using, and also can be that pathogen institute zooparasite is used the serum antibody for preparing after the immunity of this kind inactivated vaccine.Described antibacterial comprises escherichia coli, Salmonella, pasteurellosis bacillus, clostridieum welchii, tubercule bacillus, brucella, Listeria monocytogenes, secondary haemophilus, Actinobacillus pleuropneumoniae, bacillus pyocyaneus, anthrax bacillus, clostridium tetani, staphylococcus, streptococcus etc.
Described antibiotic is that all directeds toward bacteria have the antibiotic of therapeutic effect and chemicals to comprise penicillin, penbritin, carboxylic Bian penicillin, amoxicillin, streptomycin, oxytetracycline, erythromycin, Roxithromycin, doxycycline, kanamycin, amikacin, gentamycin, lincomycin, clindamycin, cephalosporins, sulfonamides antibiotic, florfenicol etc.
Described targeted drug can be that anticolibacillary serum antibody and gentamycin sulfate are combined into conjugate by PEG.
Described targeted drug can be that serum antibody and the lincomycin hydrochloride of anti-Actinobacillus pleuropneumoniae is combined into conjugate by PEG.
Described targeted drug is that anti-salmonella serum antibody and kanamycin are combined into conjugate by PEG.
Described targeted drug can be that the serum antibody and the kanamycin of anti-salmonella is combined into conjugate by PEG.
Preparation method of the present invention is: the separation and Culture of different antibacterials is identified breeding species, enrichment culture then, be prepared into oil emulsion inactivated vaccine after the deactivation, immunizing rabbit is monitored the rabbit anteserum antibody titer then, after reaching requirement, kill the rabbit blood sampling, preparation antibacterial serum antibody; The antibacterial serum antibody is mixed with antibiotic solution, add PEG6000, shake spends the night under 4 ℃, and the antibacterial serum antibody is connected product formation and precipitates with antibiotic, abandon supernatant, collecting precipitation.
In cohesive process, there is certain difference in the ratio of different serum antibodys and different medicine best combination, and (indirect elisa method monitoring antibody titer is 2 to serum antibody solution
10) and the ratio of drug solution (drug level 4mg/ml) be 1: 2～1: 4.Joint efficiency: detect through indirect elisa method, the joint efficiency of antibody is between 50%-60%; Detect by extracorporeal bacteria inhibitor test, the joint efficiency of medicine is at 80%-100%.Through identifying, 2 hydroxyls of PEG molecular end and the alkamine material in the medicine and the amino in the serum antibody form stable conjugate with covalent bonds.Targeted drug of the present invention what adopted is that the antibacterial serum antibody is a polyclonal antibody, and can not be monoclonal antibody.Thereby can not be main alternative with monoclonal antibody to the targeted drug of tumor.
Targeted drug of the present invention then major part enters antibacterial, and waste seldom then be can't help its dosage and the course of treatment accretion rate decision of medicine, but is decided by the intravital amount of bacteria of animal.
Characteristics efficient, quick-acting, low-residual that medicine of the present invention has.Efficiently be: targeted drug of the present invention also has " navigation system " except the antibacterial activity part is arranged.The present invention with antibiotic with after the antibacterium serum antibody combines, under the effect of antibody chemotactic factor in animal body, move towards the position at antibacterial place is directed, and initiatively combine rapidly with antibacterial, enter in the bacterial cell, and the entrained medicine of antibody just begins to play effectiveness.Therefore, use targeted drug of the present invention and treat bacterial disease, targeted drug is not being evenly distributed of machinery in animal body, but initiatively seek antibacterial, in therapeutic process, few by the medication amount of animal organism metabolism before the medicine sterilization, avoided the waste of medicine.The treatment bacterial disease only needs medicine seldom.The drug effect of medicine of the present invention has raising largely, and the conventional new drug of exploitation is the same with conventional medicament at present, the medicine of new drug of exploitation contacts with antibacterial and medicine and antibacterial combination do not change, accretion rate decision by medicine, need the higher blood drug level and the long course of treatment, most of medicine can be fallen by metabolism in the medication process.Targeted drug then can major part enter antibacterial, is decided by the intravital amount of bacteria of animal its dosage and the course of treatment in the process of medication, thereby does not have the drug metabolism speed issue.Its drug effect of targeted drug of the present invention even the curative effect when just having used than this antibiotic are not bad, and will become the important means of eliminating present bacterial drug resistance.
Quick-acting being: because conjugate is initiatively divided a word with a hyphen at the end of a line to the antibacterial orientation, accelerated the speed that medicine enters bacterial cell greatly, and because antibody molecule is bigger, simultaneously in conjunction with a plurality of drug molecules, therefore after conjugate enters bacterial cell, because more drug molecule, killing bacteria are rapidly arranged.Therefore, therapeutic effect often gets instant result, and As the medicine took effect, the symptoms lessened.
Low-residual is: antibody carries medicine, directly enters bacterial cell, medicine can be in the animal body tissue stops for a long time, alleviated greatly medicine to the infringement of animal body histoorgan and eliminate substantially drug residue phenomenon.And because efficient, total dosage is few owing to quick-acting, short treating period, and these all help reducing animal body Chinese medicine residual quantity.
Antibacterium serum antibody of the present invention combines with PEG with antibiotic, can make combine with serum antibody and medicine stable; PEG can also make serum antibody concentrate and form precipitation in addition, thereby makes serum antibody and drug conjugates energy and solution separating; Because the dissolubility of PEG in water is very big, liquid PEG can be miscible with any ratio and water, even high molecular weight PEGs dissolubility in water can reach more than 50%.Simultaneously, PEG dissolves in the multiple organic solvents such as ethanol, acetaldehyde, alkanolamide, amide, amine, chlorinated hydrocabon, aromatic hydrocarbon, ester, glycol ester, glycol ether ester, ketone, organic acid, anhydride and phenol, therefore, PEG can be dissolved in the mixed liquor of serum antibody and medicine well, connect serum antibody and medicine,, can merge with bacterial cell membrane again with after drug conjugates contacts antibacterial at serum antibody, make serum antibody and drug conjugates can enter bacterial cell smoothly; And PEG has extremely low toxicity, can not have side effects to animal body.
Targeted drug of the present invention can be made into injection or oral formulations, as capsule, and tablet.
The specific embodiment
Embodiment 1
To select the sick pig of HUANGBAI(sic) dysentery symptom from the pig farm, the aseptic mesenteric lymph node of taking the disease pig, be inoculated on the maconkey agar with subregion setting-out method, put in 37 ℃ of calorstats and cultivated 24 hours, red bacterium colony on the picking maconkey agar then, cultivate in inoculation LB fluid medium mid-37 ℃ of calorstats that the biochemical test with identification of escherichia coli identifies escherichia coli after 24 hours, then with the escherichia coli that identify as strain, cultivate in a large number with the LB fluid medium, use the formalin-inactivated culture then.After testing, behind the complete inactivation, be water with deactivation liquid, with 7
#White oil is an oil phase, and the escherichia coli oil emulsion inactivated vaccine is made in emulsifying, reuse escherichia coli oil emulsion inactivated vaccine immunizing rabbit, every 7 days, to adopt Sanguis Leporis seu oryctolagi and monitor the rabbit anteserum antibody titer with indirect elisa method, the serum antibody indirect ELISA titer in Sanguis Leporis seu oryctolagi reaches 2
10After, kill the rabbit blood sampling, with adopting Sanguis Leporis seu oryctolagi put place 2 hours in 37 ℃ of calorstats after, draw the liquid of separating out, just made at colibacillary serum antibody.With serum antibody and gentamicin sulfate solution by a certain percentage (1: 2) mix, add the PEG6000 of mixed liquor cumulative volume 15% (W/V), shake, after PEG6000 is fully dissolved, spend the night under 4 ℃, antibody is connected product and forms precipitation with medicine, with 6000 rev/mins of speed after centrifugal 15 minutes, abandon supernatant, collecting precipitation adds a certain amount of sterile saline, dissolution precipitation, the injection that can be used for clinical practice is promptly made in packing.Measure conjugate MIC: the precipitation of gained is used and combined the preceding isopyknic normal saline of gentamicin sulfate solution that adds and dilute, undertaken doubling dilution to 10 with escherichia coli fluid medium LB culture medium by 10 times then
-10, compare with gentamicin sulfate solution simultaneously, carry out doubling dilution to 10 for same 10 times
-10, each dilution factor of conjugate diluent and gentamicin sulfate solution diluent is all inoculated the equivalent escherichia coli then.Cultivate observed result after 24 hours in 37 ℃ of calorstats.The result shows: gentamicin sulfate solution is diluted to 10
-3The time, lose bacteriostasis; Conjugate solution dilution to 10
-8The time, lose bacteriostasis.The MIC of the MIC of gentamicin sulfate solution and conjugate solution is widely different.
Embodiment 2
The animal disease model therapeutic test:
The conjugate of embodiment 1 (be targeted drug of the present invention, down with) precipitation is diluted to normal saline and combines preceding gentamicin sulfate solution equal-volume, standby.Buy 60 of white mice big or small about healthy 20g, be divided into 6 groups at random, use 5LD
50/ only all white mice of escherichia coli amount inoculation, begin treatment when treating that the symptom performance appears in white mice, first group as blank; Use the anticolibacillary serum Antybody therapy for second group;
Use the treatment of gentamycin sulfate by specification usage and dosage for the 3rd group; Use the identical conjugate treatment of gentamycin sulfate dosage for the 4th group; The 5th group with being equivalent to the identical conjugate treatment of 1/10 gentamycin sulfate dosage; The 6th group with being equivalent to the identical conjugate treatment of 1/100 gentamycin sulfate dosage.Observe therapeutic outcome.The result shows: first group, second group, the 3rd group white mice is all dead; The 4th group, the 5th group white mice all fully recovered; The 6th group has 8 white mice recoveries from illness, 2 death.
Embodiment 3
The clinical treatment test:
The conjugate of Application Example 1 respectively in Changsha, ground such as Ningxiang, Xiang Tan, Yongzhou, Chaling chooses 10 pig farms that have the yellow and white dysentery of piglet eqpidemic disease, successively there is the piglet of the symptom of having loose bowels to treat to 500, cure 490, new cases, cure the amount of conjugate in every used targeted drug of the present invention of pig, only be equivalent to the gentamycin sulfate of 8 kilounits; Cure the amount of conjugate in every used targeted drug of pig for disease time case more of a specified duration, only be equivalent to the gentamycin sulfate of 10,000 6 kilounits.10 pigs of curing have not been stopped yet and having had loose bowels, and also have the mixed infection of other eqpidemic diseases after diagnosing.
Embodiment 4
With porcine contagious pleuropneumonia Serum Antibody Detection test kit pig is carried out the porcine contagious pleuropneumonia Serum Antibody Detection, select the male sick pig of porcine contagious pleuropneumonia serum antibody from the pig farm, the aseptic lungs of taking the disease pig, be inoculated into pathological material of disease and gold-coloured staphylococci on the chocolate agar simultaneously with the setting-out method, put in 37 ℃ of calorstats and cultivated 72 hours, the one satellite colony of gold-coloured staphylococci on the picking chocolate agar then, cultivate after 24 hours in the mid-37 ℃ of calorstats of inoculation fluid medium and identify Actinobacillus pleuropneumoniae with the biochemical test of identifying Actinobacillus pleuropneumoniae, then with identify Actinobacillus pleuropneumoniae as strain, cultivate in a large number with fluid medium, use the formalin-inactivated culture then.After testing, behind the complete inactivation, be water with deactivation liquid, with 7
#White oil is an oil phase, and the Actinobacillus pleuropneumoniae oil emulsion inactivated vaccine is made in emulsifying, reuse Actinobacillus pleuropneumoniae oil emulsion inactivated vaccine immune health pig, every 7 days, adopt Sanguis sus domestica indirect elisa method monitoring pig serum antibody titer, the serum antibody indirect ELISA titer in Sanguis sus domestica reaches 2
10After, kill the pig blood sampling, with adopting Sanguis sus domestica put place 2 hours in 37 ℃ of calorstats after, draw the liquid of separating out, just made serum antibody at Actinobacillus pleuropneumoniae.With serum antibody and lincomycin hydrochloride solution (4mg/ml) by a certain percentage (1: 3) mix, add the PEG6000 of mixed liquor cumulative volume 20% (W/V), shake, after PEG6000 is fully dissolved, spend the night under 4 ℃, antibody is connected product and forms precipitation with medicine, with 6000 rev/mins of speed after centrifugal 15 minutes, abandon supernatant, collecting precipitation adds a certain amount of sterile saline, dissolution precipitation, the injection that can be used for clinical practice is promptly made in packing.
Respectively in Changsha, ground such as Ningxiang, Xiang Tan, Yongzhou, Chaling choose 10 male pig farms of porcine contagious pleuropneumonia serum antibody, successively the positive sick pigs of 400 porcine contagious pleuropneumonia serum antibodys are treated.After three months, with porcine contagious pleuropneumonia Serum Antibody Detection test kit treatment disease pig is carried out the porcine contagious pleuropneumonia Serum Antibody Detection once more, wherein the contagious pleuropneumonia serum antibody of 360 pigs transfers feminine gender to, and tiring of the pleuropneumonia serum antibody of other 40 sick pigs also greatly reduces.The result proves that porcine contagious pleuropneumonia serum antibody and lincomycin hydrochloride conjugate have good curative effect to porcine contagious pleuropneumonia.
Embodiment 5
To select the sick chicken of Pullorum Disease symptom from chicken house, the aseptic liver of taking the disease chicken, be inoculated on the maconkey agar with subregion setting-out method, put in 37 ℃ of calorstats and cultivated 24 hours, white colony on the picking maconkey agar then cultivates in the mid-37 ℃ of calorstats of inoculation LB fluid medium that the biochemical test with the evaluation Salmonella identifies Salmonella after 24 hours, then with the Salmonella that identifies as strain, cultivate in a large number with the LB fluid medium, use the formalin-inactivated culture then.After testing, behind the complete inactivation, be water with deactivation liquid, with 7
#White oil is an oil phase, and the Salmonella oil emulsion inactivated vaccine is made in emulsifying, reuse Salmonella oil emulsion inactivated vaccine immune health chicken, every 7 days, to adopt Sanguis Gallus domesticus and monitor the chicken serum antibody titer with indirect elisa method, the serum antibody indirect ELISA titer in Sanguis Gallus domesticus reaches 2
10After, kill the chicken blood sampling, with adopting Sanguis Gallus domesticus put place 2 hours in 37 ℃ of calorstats after, draw the liquid of separating out, just made serum antibody at anti-salmonella.With anti-salmonella serum antibody and kanamycin solution (4mg/ml) by a certain percentage (1: 4) mix, add the PEG6000 of mixed liquor cumulative volume 18% (W/V), shake, after PEG6000 is fully dissolved, spend the night under 4 ℃, antibody is connected product and forms precipitation with antibiotic, with 6000 rev/mins of speed after centrifugal 15 minutes, abandon supernatant, collecting precipitation adds a certain amount of sterile saline, dissolution precipitation, the injection that can be used for clinical practice is promptly made in packing.Measure conjugate MIC: the precipitation of gained is used and combined the preceding isopyknic normal saline of kanamycin solution that adds and dilute, undertaken doubling dilution to 10 with Salmonella fluid medium LB culture medium by 10 times then
-10, compare with kanamycin solution simultaneously, carry out doubling dilution to 10 for same 10 times
-10, each dilution factor of conjugate diluent and kanamycin solution dilution liquid is all inoculated the equivalent Salmonella then.Cultivate observed result after 24 hours in 37 ℃ of calorstats.The result shows: kanamycin solution dilution to 10
-2The time, lose bacteriostasis; Conjugate solution dilution to 10
-9The time, lose bacteriostasis.The MIC of the MIC of kanamycin solution and conjugate solution is widely different.
Claims (9)
1. targeted drug that is used for treating bacteriosis, it is characterized in that: active component is the conjugate that antibacterium serum antibody and the crosslinked structure of antibiotic form;
By the stable conjugate of Polyethylene Glycol be combined into, the antibacterial serum antibody that is adopted is a polyclonal antibody between antibacterium serum antibody and the antibiotic.
2. a kind of targeted drug that is used for treating bacteriosis according to claim 1 is characterized in that: described Polyethylene Glycol is a polyethylene glycol 6000.
3. a kind of targeted drug that is used for treating bacteriosis according to claim 1 and 2, it is characterized in that: described antibacterium serum antibody is the serum antibody for preparing behind the inactivated vaccine immunizing rabbit of pathogen preparation using, or pathogen institute zooparasite is used the serum antibody for preparing after the immunity of this kind inactivated vaccine.
4. a kind of targeted drug that is used for treating bacteriosis according to claim 1 is characterized in that: described antibacterial is escherichia coli, Salmonella, pasteurellosis bacillus, clostridieum welchii, tubercule bacillus, brucella, Listeria monocytogenes, secondary haemophilus, Actinobacillus pleuropneumoniae, bacillus pyocyaneus, anthrax bacillus, clostridium tetani, staphylococcus or streptococcus; Described antibiotic is penicillin, penbritin, carboxylic Bian penicillin, amoxicillin, streptomycin, oxytetracycline, erythromycin, Roxithromycin, doxycycline, kanamycin, amikacin, gentamycin, lincomycin, clindamycin, cephalosporins, sulfonamides antibiotic or florfenicol.
5. a kind of targeted drug that is used for treating bacteriosis according to claim 1 is characterized in that: described targeted drug is that anticolibacillary serum antibody and gentamycin sulfate are combined into conjugate by PEG.
6. a kind of targeted drug that is used for treating bacteriosis according to claim 1 is characterized in that: described targeted drug is that serum antibody and the lincomycin hydrochloride of anti-Actinobacillus pleuropneumoniae is combined into conjugate by PEG.
7. a kind of targeted drug that is used for treating bacteriosis according to claim 1 is characterized in that: described targeted drug is that anti-salmonella serum antibody and kanamycin are combined into conjugate by PEG.
8. the described a kind of preparation method that is used for the targeted drug for the treatment of bacteriosis of claim 1, it is characterized in that: the separation and Culture of different antibacterials is identified, breeding species, enrichment culture is prepared into oil emulsion inactivated vaccine, then immunizing rabbit after the deactivation then, monitoring rabbit anteserum antibody titer, after reaching requirement, kill the rabbit blood sampling, preparation antibacterial serum antibody; The antibacterial serum antibody is mixed with antibiotic solution, add PEG6000, shake spends the night under 4 ℃, and the antibacterial serum antibody is connected product formation and precipitates with antibiotic, abandon supernatant, collecting precipitation.
9. a kind of preparation method that is used for the targeted drug for the treatment of bacteriosis according to claim 8 is characterized in that: ratio is 1: 2～1: 4 between antibacterial serum antibody solution and the antibiotic solution; Described antibacterial serum antibody solution, its indirect elisa method monitoring antibody titer is 2
10Described antibiotic concentration 4mg/ml.
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| AU2009203426C1 (en) * | 2008-01-10 | 2012-05-31 | Shionogi & Co., Ltd. | Antibody directed against PcrV |
| CN106053805B (en) * | 2016-07-21 | 2018-09-21 | 新疆农垦科学院 | It is a kind of to be used to detect sensitizing type aptamer test strips of salmonella and preparation method thereof |
| CN112402381B (en) * | 2020-11-19 | 2023-02-28 | 广州一品红制药有限公司 | Clindamycin palmitate hydrochloride particle composition and preparation method thereof |
| CN114042152A (en) * | 2021-11-30 | 2022-02-15 | 山东滨州博莱威生物技术有限公司 | Duck enteritis salmonellosis inactivated vaccine and preparation method thereof |
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