CN103948930B - A kind of poultry compound medicine containing Radix Paeoniae Rubra and beta-lactam antimicrobial drug - Google Patents
A kind of poultry compound medicine containing Radix Paeoniae Rubra and beta-lactam antimicrobial drug Download PDFInfo
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- CN103948930B CN103948930B CN201410202810.5A CN201410202810A CN103948930B CN 103948930 B CN103948930 B CN 103948930B CN 201410202810 A CN201410202810 A CN 201410202810A CN 103948930 B CN103948930 B CN 103948930B
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- radix paeoniae
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- paeoniae rubra
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Fodder In General (AREA)
Abstract
The present invention relates to a kind of containing Radix Paeoniae Rubra with the poultry compound medicine of beta-lactam class antimicrobial drug, be made up of the raw material of following weight portion: beta-lactam class antimicrobial drug 3 30 parts, Radix Paeoniae Rubra 5 200 parts;Described beta-lactam class antimicrobial drug is amoxicillin, ceftriaxone sodium or ceftiofur sodium.The present invention can the reverse bacterial drug resistance to antimicrobial drug, thus improve the therapeutic effect of antimicrobial drug.According to a conventional method this compound medicine is made powder, tablet, oral liquid or granule, add in animal and fowl fodder according to the addition of 0.1 7g principal agent/kg feedstuff and feed, drug cost and drug residue can be greatly reduced, create higher economic benefit for raiser, also ensure that food safety simultaneously.
Description
Technical field
The invention belongs to poultry escherichia coli and Salmonella infection treatment technology field, particularly relate to a kind of containing Radix Paeoniae Rubra
Poultry compound medicine with beta-lactam antimicrobial drug.
Background technology
Fowl salmonellosis (Avian salmonellosis) is by one or more Salmonellas in Salmonella
The general name of caused poultry disease.Difference according to pathogen antigen structure can be divided into 3 classes: Pullorum Disease, avian typhoid and fowl are secondary
Typhoid fever.Wherein Pullorum Disease and avian typhoid Salmonella have host specificity, mainly cause chicken and turkey morbidity;And avian paratyphoid is husky
Door Salmonella then can extensively infect many animals and people, is mankind's Salmonella infection and food by its poultry polluted and products thereof
One of main source of poisoning.Fowl salmonellosis is commonly formed considerably complicated propagation circulation.Sick fowl and the fowl that carries disease germs are main
The source of infection, can pass through digestive tract, respiratory tract or eye conjunctiva horizontal transmission, can infect poult, cause big portion after ovum vertical transmission
Dividing death, poultry carries disease germs for a long time, the ovum that then output is carried disease germs, if hatching in this, as hatching egg, then and the generation can gone round and begun again
In generation, passes on from one to another, and causes fowl salmonellosis to be difficult to purify in chicken group, causes serious economic loss.Owing to Salmonella is chicken group
Middle pollution face is big, and is easily generated drug resistance, and immune effect of vaccine in the market is the most undesirable.Therefore, breeder flock quarantine, medicine
Thing controls, environment disinfected purifies, strengthen feeding and management and health and epidemic prevention is still and controls and prevent Salmonella from entering food chain
Essential measure.Chickling is drunk 0.01% potassium permanganate solution or other drug 1~carries out chemoprophylaxis in 2 days after going out shell.This bacterium pair
Common drug produces drug resistance, forces and has to carry out various medicine in production and be used alternatingly, in the hope of preferably controlling fastbacteria.
This bacterium produces stronger drug resistance to aminoglycoside medicaments at present, and aminoglycoside inactive enzyme is to these antibacterials molecules
In some protection antibacterial activity necessary to group modify so that it is affinity ribosomal with target site is greatly lowered.
These inactive enzymes include aminoglycoside acyltransferase (AAC), aminoglycoside adenylyl transferase (AAD), aminoglycoside phosphorus
Acid transferring enzyme (APH), gland nucleotidyltransferase (ANT) etc..The most it is found that not in the fastbacteria of many aminoglycosides
Inactive enzyme with characteristic.
Escherichia coli are common conditioned pathogens, are also a kind of diseases often sent out, and it primary can cause the acute deteriorated blood of chicken
The multiple location severe infections such as disease, peritonitis, hepatitis, pneumonia, enteritis, also can secondary or mixed send out in virosis, cause to aquaculture
Huge economic loss.Amoxicillin, ampicillin, ceftiofur, ceftriaxone, amoxicillin/clavulanate, ammonia benzyl west
The beta-lactam nucleus class antibiotic such as woods/sulbactam are the conventional important drugs preventing and treating this disease, along with the cultivation intensive journey of scale
Degree is more and more big, and medication is more and more spread unchecked, and its Resistant strain is the most, and the report about Drug Resistance of E. coli is the most more.
Research confirms, one of main mechanism of drug resistance is to produce beta-lactamase, especially extended spectrumβ-lactamase (Extended-
Spectrum β-lactamase, ESBLs), this enzyme can hydrolyze beta-lactam nucleus more by force and rapidly, makes this kind of antibiotic lose
Antibacterial activity.ESBLs is the main enzyme type of beta-lactamase, and it is not only to cephalo three generations and aztreonam drug resistance, and to ammonia
Base glucosides class, quinolones and sulfonamides are crossing drug resistant, only to carbapenems, a mould alkenes medicaments insensitive.Many documents
It has been reported that colibacillary multi-drug resistant with produce ESBLs have substantial connection, both at home and abroad to more pay close attention to.Inventor is
The detection of food animal source pathogenic bacterium ESBLs, extraction, enzyme are closely carried out to the percent hydrolysis of antibiotic and sulbactam, Tazobactam Sodium
And the research such as the enzyme protection effect that presses down of Chinese medicine, drug sensitive test colibacillary to part ESBLs shows, its multidrug resistant rate is bright
Aobvious higher than non-ESBLs bacterial strain.It addition, result also shows that product ESBLs bacterial strain is not only tight to third generation cephalosporins such as ceftiofurs
Weight drug resistance, and also antimicrobial drug drug resistance multiple to fluoroquinolones, aminoglycoside and sulfonamides, fosfomycin etc., in serious
Multidrug resistant.Inventor is separated to resistance to fosfomycin in producing ESBLs bacterial strain and produces the escherichia coli of fosA3 drug resistant gene, more strengthens
The drug resistance of antibacterial.
Salmonella and colibacillary drug resistance cause raiser's drug cost to increase, and treatment extends the course for the treatment of, and poultry are dead
Rate of dying increases, and brings bigger economic loss to production, and increases poultry drug residue risk.Therefore, actual production is needed badly
A kind of to regardless of whether the Salmonella of drug resistance and escherichia coli can have a medicine of preferable therapeutical effect, and treatment can be shortened treat
Journey, reduces mortality rate, reduces economic loss and reduces drug residue, creating higher economic benefit for raiser, also ensure people
Class healthy and safe.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of poultry containing Radix Paeoniae Rubra and beta-lactam antimicrobial drug with multiple
Side's medicine, it can kill antibacterial quickly, overcome weak curative effect that antimicrobial drug treatment causes due to drug resistance problems, consumption big,
The defect that residual is high and cost is high, it is to avoid simple Chinese medicine sterilizing spectrum is narrow, sterilize slow problem.
For solving above technical problem, the present invention by the following technical solutions: a kind of resist containing Radix Paeoniae Rubra and beta-lactam
The poultry compound medicine of bacterium medicine, is made up of the raw material of following weight portion: beta-lactam antimicrobial drug 3-30 part, Radix Paeoniae Rubra 5-200
Part.
Described beta-lactam antimicrobial drug is amoxicillin, ceftriaxone sodium or ceftiofur sodium.
Further, described compound medicine is made up of the raw material of following weight portion: amoxicillin 3-20 part and Radix Paeoniae Rubra 40-
180 parts, or ceftiofur sodium 3-25 part and Radix Paeoniae Rubra 30-190 part.
Described compound medicine is prepared as powder, tablet, oral liquid or granule.
The preparation method of described compound medicine is: Radix Paeoniae Rubra pulverized 60 mesh sieves, then mixes with the antimicrobial drug of powder,
It is prepared as powder, tablet, oral liquid or granule according to a conventional method.
The drug resistance problems existed for current poultry escherichia coli and Salmonella infection, inventor utilizes Lactiflora
Compound medicine is formed with antimicrobial drug.Research proves, after adding Radix Paeoniae Rubra in antimicrobial drug, it is possible to the reverse bacterial drug resistance to antimicrobial drug
Property, thus improve the therapeutic effect of antimicrobial drug.According to a conventional method this compound medicine is made powder, tablet, oral liquid or granule
Agent, adds in animal and fowl fodder according to the addition of 0.1-7g principal agent/kg feedstuff and feeds, can be greatly reduced drug cost and
Drug residue, creates higher economic benefit for raiser, also ensure that food safety simultaneously.
Detailed description of the invention
One, the Radix Paeoniae Rubra drug resistance inversion Effect study to antimicrobial drug
Antimicrobial drug itself has treatment escherichia coli and the effect of Salmonella, but owing to producing the escherichia coli of drug resistant gene
With Salmonella, there is stronger drug resistance, cause antimicrobial drug not show in the case of normal using dosage and preferably control
Therapeutic effect.
1, to colibacillary drug resistance inhibition test after Radix Paeoniae Rubra mixes with antimicrobial drug
96 orifice plates use microtest tube doubling dilution, first determines antimicrobial drug to producing ESBLs and fosA3 drug resistance base
Minimal inhibitory concentration and the Radix Paeoniae Rubra of the e. coli strains of cause are antibacterial to the Asia producing ESBLs and fosA3 drug resistant gene e. coli strains
Concentration, add the most in the medium the Radix Paeoniae Rubra of subinhibitory concentration reuse microtest tube doubling dilution cultivate measure antibacterial
The minimal inhibitory concentration of medicine;Utilize continuous passage method added with same subinhibitory concentration Radix Paeoniae Rubra and the cultivation of same concentration antimicrobial drug
Base carries out Secondary Culture, until the antimicrobial drug minimum observed is antibacterial to product ESBLs and fosA3 drug resistant gene e. coli strains
Concentration with pass on before compared with diminish more than 4 times, can be judged as that Radix Paeoniae Rubra has drug resistance inversion effect to antibacterial medical instrument.Result of the test is united
Meter is as shown in table 1:
Table 1 subinhibitory concentration (0.5g/mL) Radix Paeoniae Rubra passes on and causes the change producing ESBLs and fosA3 escherichia coli Western medicine MIC
(μg/mL)。
As seen from the above table, antimicrobial drug all reduces more than 4 times to the minimal inhibitory concentration of antibiotic-resistance E. coli, i.e. can determine whether be
Radix Paeoniae Rubra has drug resistance inversion effect to producing ESBLs and fosA3 drug resistant gene escherichia coli.
2, drug resistance inhibition test to Salmonella after Radix Paeoniae Rubra mixes with antimicrobial drug
96 orifice plates use microtest tube doubling dilution, first determines the antimicrobial drug minimum to drug resistance salmonella strain
Mlc and the Radix Paeoniae Rubra subinhibitory concentration to drug resistance salmonella strain, add the Radix Paeoniae Rubra of subinhibitory concentration the most in the medium
Reuse microtest tube doubling dilution and cultivate the minimal inhibitory concentration measuring antimicrobial drug;Utilize continuous passage method added with same
The culture medium of sample subinhibitory concentration Radix Paeoniae Rubra and same concentration antimicrobial drug carries out Secondary Culture to Salmonella persister, until seeing
The antimicrobial drug minimal inhibitory concentration measured with pass on before compared with diminish more than 4 times, can be judged as that antibacterial medical instrument is had resistance to by Radix Paeoniae Rubra
Medicine reverse effect.Result of the test statistics is as shown in table 2:
Table 2 subinhibitory concentration (0.5g/mL) Radix Paeoniae Rubra passes on the change (μ g/mL) causing drug resistance Salmonella Western medicine MIC.
As seen from the above table, antimicrobial drug all reduces more than 4 times to the minimal inhibitory concentration of drug resistance Salmonella, i.e. can determine whether be
Radix Paeoniae Rubra has drug resistance inversion effect to drug resistance Salmonella.
Two, the application example of compound medicine of the present invention
Embodiment 1-embodiment 8 is prepared: after Radix Paeoniae Rubra was pulverized 60 mesh sieves, as base according to table 3 formula and following methods
Plinth raw material, then mix, according to a conventional method, by compound medicine system during ratio puts into blender by weight with the antimicrobial drug of powder
Standby one-tenth formulation products.
The formula of table 3 embodiment 1-8 and preparation dosage form
Numbering | Antimicrobial drug | Radix Paeoniae Rubra | Dosage form |
Embodiment 1 | Amoxicillin 3g | 120g | Tablet |
Embodiment 2 | Amoxicillin 10g | 90g | Powder |
Embodiment 3 | Amoxicillin 14g | 40g | Oral liquid |
Embodiment 4 | Amoxicillin 20g | 180g | Granule |
Embodiment 5 | Ceftiofur sodium 13g | 190g | Tablet |
Embodiment 6 | Ceftiofur sodium 15g | 85g | Powder |
Embodiment 7 | Ceftiofur sodium 3g | 5g | Oral liquid |
Embodiment 8 | Ceftiofur sodium 25g | 30g | Granule |
Above-described embodiment is obtained compound medicine product and has carried out following experiment by inventor:
1, the compound medicine product of the embodiment 1-4 gained efficacy experiment to chicken escherichia coil disease
Clinical symptoms: Guigang, Guangxi chicken house, 25 Day-old Broiler Chickens, there is fragmentary death in chicken group, cuts open the indivedual chickens of inspection and bag occurs
Pericardium liver pathological change, typical bacillus coli feature.
Laboratory diagnosis: take pathologic liver dye sheet, Gram’s staining, basis of microscopic observation, it is seen that red gram-negative
Property bacillus;Tentatively it is judged as bacillus coli.Being cultivated by escherichia coli, biochemical test differentiates, it is judged that it is big that chicken infects
Enterobacteria disease, PCR expands, it was demonstrated that produce the ESBLs drug resistant gene having TEM type.
Test therapeutic regimen: morbidity chicken group is divided into 6 groups of administrations, first group by embodiment 1 according to the interpolation of 7g/kg feedstuff
Amount is administered, and second group is administered according to the addition of 2g/kg feedstuff by embodiment 2, raises according to 0.8g/kg by embodiment 3 for the 3rd group
The addition of material is administered, and the 4th group is administered according to the addition of 2g/kg feedstuff by embodiment 4;Use amoxicillin powder for 5th group
Being administered according to the addition of 0.2g/kg feedstuff, the 6th group is administered according to the addition of 4g/kg feedstuff with the thick powder of Radix Paeoniae Rubra;Above
Six groups of therapeutic regimens the most persistently use 5 days.
Staining effect: after chicken group's medication of first group to the 4th group, sick chicken feed intake rises, and dead chicken no longer occurs, continues
Using 3 days, chicken group be almost recovered;After chicken group's medication of the 5th group 2 days, chicken group's majority is the most unhealthy, still has indivedual chicken death, continues
Continuous use 3 days, chicken death phenomenon is still without being effectively controlled;After chicken group's medication of the 6th group 2 days, the not biggest bright of chicken group
Aobvious change, is continuing with 3 days, and chicken death phenomenon is still without being effectively controlled.Visible, the compound medicine curative effect containing Radix Paeoniae Rubra is excellent
In folk prescription.
2, the efficacy experiment that the meat-type duck of 20 ages in days is suffered from diarrhoea by the compound medicine product of embodiment 5-8 gained
Clinical symptoms: duck field, Nanning, 20 age in days meat-type duck, duck group draws watery stools, has and significantly do not disappear in feces
The feedstuff changed.Duck group material feeding but the longest, indivedual serious ducks of suffering from diarrhoea gradually occur that foot is soft slowly dead.
Cuing open inspection pathological changes: the duck that dies of illness dehydration ratio is more serious, indivedual ducks are the biggest, duck liver enlargement, hyperemia, the liver of part duck
Having white films on dirty, air bag is muddy, and tentative diagnosis is escherichia coli or duck oromeningitis.
Test therapeutic regimen: morbidity duck group divides six groups of administrations, first group by embodiment 5 according to the addition of 3g/kg feedstuff
Being administered, second group is administered according to the addition of 1.3g/kg feedstuff by embodiment 6, raises according to 0.5g/kg by embodiment 7 for the 3rd group
The addition of material is administered, and the 4th group is administered according to the addition of 0.45g/kg feedstuff by embodiment 8;Use ceftiofur sodium for 5th group
Powder is administered according to the addition of 0.2g/kg feedstuff, and the 6th group is administered according to the addition of 5g/kg feedstuff with the thick powder of Radix Paeoniae Rubra;
Above six groups of therapeutic regimens the most persistently use 5 days.
Using effect is fed back: after first group to the 4th group medication 2 days, and sick duck no longer draws watery stools, formed stools, no longer
Dead duck occur, be continuing with 3 days, duck group be almost recovered;After 5th group of medication 2 days, duck group's DeGrain, the most still draws water
Sample feces, containing indigested feedstuff, is continuing with 3 days, somewhat takes a turn for the better, but the best thorough, and dilute watery stools is still
Occurring, using the compound medicine of embodiment 6 gained instead, be continuing with 2 days, be just almost recovered, re-use 1 day, feces all transfers to
Normally;After 6th group of medication 2 days, duck does not has the biggest remarkable improvement, is continuing with 3 days, and the duck phenomena of mortality are still without being had
Effect controls.Visible, the curative effect that duck is suffered from diarrhoea by compound medicine containing Radix Paeoniae Rubra is better than folk prescription.
3, embodiment 1-4 obtains the compound medicine product efficacy experiment to Salmonella gallinarum disease
Clinical symptoms: Liuzhou chicken house, 13 age in days laying hens, there is dysentery, row's white, pasty state loose stool, anus in chicken group
Tomentum fecal pollution around, has Calx sample lump, the shriek sending misery having, and has the phenomena of mortality.Cut open the indivedual chickens of inspection
Hepatomegaly be kermesinus to darkviolet, or slightly khaki, matter is crisp fragile, and surface is dispersed in or gathers greyish white, the downright bad point of lark,
Sometimes it is red petechia, typical Salmonella genius morbi.
Laboratory diagnosis: take pathologic liver dye sheet, Gram’s staining, basis of microscopic observation, it is seen that red gram-negative
Property bacillus;Tentatively it is judged as Salmonella disease.Being cultivated by Salmonella, biochemical test differentiates, it is judged that chicken infects for sand
Door Salmonella disease, drug sensitive test result is judged as persister Salmonella according to NCCLS standard.
Test therapeutic regimen: morbidity chicken group is divided into 6 groups of administrations, first group by embodiment 1 according to the interpolation of 7g/kg feedstuff
Amount is administered, and second group is administered according to the addition of 2g/kg feedstuff by embodiment 2, raises according to 0.8g/kg by embodiment 3 for the 3rd group
The addition of material is administered, and the 4th group is administered according to the addition of 2g/kg feedstuff by embodiment 4;Use amoxicillin powder for 5th group
Being administered according to the addition of 0.2g/kg feedstuff, the 6th group is administered according to the addition of 4g/kg feedstuff with the thick powder of Radix Paeoniae Rubra;Above
Six groups of therapeutic regimens the most persistently use 5 days.
Staining effect: after chicken group's medication of first group to the 4th group, sick chicken feed intake rises, and dead chicken no longer occurs, continues
Using 3 days, chicken group be almost recovered;After chicken group's medication of the 5th group 2 days, chicken group's majority is the most unhealthy, still has indivedual chicken death, continues
Continuous use 3 days, chicken death phenomenon is still without being effectively controlled;After chicken group's medication of the 6th group 2 days, the not biggest bright of chicken group
Aobvious change, is continuing with 3 days, and chicken death phenomenon is still without being effectively controlled.Visible, the compound medicine curative effect containing Radix Paeoniae Rubra is excellent
In folk prescription.
Claims (3)
1. one kind contains Radix Paeoniae Rubra and the poultry compound medicine of beta-lactam antimicrobial drug, it is characterised in that by following weight portion
Raw material composition: beta-lactam antimicrobial drug 3-30 part, Radix Paeoniae Rubra 5-200 part;Described beta-lactam antimicrobial drug is A Moxi
Woods or ceftiofur sodium.
Poultry compound medicine containing Radix Paeoniae Rubra and beta-lactam antimicrobial drug the most according to claim 1, its feature exists
In, described compound medicine is made up of the raw material of following weight portion: amoxicillin 3-20 part and Radix Paeoniae Rubra 40-180 part, or cephalo thiophene
Furan sodium 3-25 part and Radix Paeoniae Rubra 30-190 part.
3. according to the poultry compound medicines containing Radix Paeoniae Rubra and beta-lactam antimicrobial drug according to any one of claim 1-2
Thing, it is characterised in that described compound medicine is prepared as powder, tablet, oral liquid or granule.
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CN104306881A (en) * | 2014-10-10 | 2015-01-28 | 天津瑞贝特科技发展有限公司 | Injection for preventing and treating poultry escherichia coli diseases and preparation method of injection |
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