CN103948930A - Red paeonia/beta-lactam-antibacterial-agent-containing compound medicine for livestock and fowl - Google Patents
Red paeonia/beta-lactam-antibacterial-agent-containing compound medicine for livestock and fowl Download PDFInfo
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
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Abstract
The invention relates to a red paeonia/beta-lactam-antibacterial-agent-containing compound medicine for livestock and fowl, which is prepared from the following raw materials in parts by weight: 3-30 parts of beta-lactam antibacterial agent and 5-200 parts of red paeonia. The beta-lactam antibacterial agent is amoxicillin, ceftriaxone sodium or ceftiofur sodium. The drug resistance of bacteria to the antibacterial agent can be reversed, thereby enhancing the treatment effect of the antibacterial agent. The compound medicine can be prepared into powder, tablets, oral liquids or granules by a conventional method, and 0.1-7g of the main medicine is added to every kilo of feed for livestock and fowl for feeding; and the feed with the compound medicine can greatly lower the medicine cost and medicine residue, create higher economic benefit for farmers and ensure the food safety.
Description
Technical field
The invention belongs to poultry escherichia coli and Salmonella infection treatment technology field, relate in particular to a kind of poultry compound medicine that contains Radix Paeoniae Rubra and beta-lactam antimicrobial drug.
Background technology
Fowl salmonellosis (Avian salmonellosis) is the general name by the caused poultry disease of one or more Salmonellas in Salmonella.Can be divided into 3 classes according to the difference of pathogen antigen structure: Pullorum Disease, avian typhoid and avian paratyphoid.Wherein Pullorum Disease and avian typhoid Salmonella have host specificity, mainly cause chicken and turkey morbidity; Avian paratyphoid Salmonella can extensively infect many animals and people, and being subject to poultry of its pollution and products thereof is one of main source of mankind's Salmonella infection and alimentary toxicosis.The propagation circulation that the normal formation of fowl salmonellosis is quite complicated.Sick fowl and the fowl that carries disease germs are the main sources of infection, can pass through digestive tract, respiratory tract or eye conjunctiva horizontal transmission, after ovum vertical transmission, can infect poult, cause most of death, poultry carries disease germs for a long time, the ovum that then output is carried disease germs, if hatch as hatching egg using this, that can go round and begin again is handed down from age to age, and causes fowl salmonellosis in chicken group, to be difficult to purify, and causes serious economic loss.Because Salmonella pollution face in chicken group is large, and easily produce drug resistance, immune effect of vaccine is in the market all undesirable.Therefore, breeder flock quarantine, medicine control, environment disinfected purification, reinforcement feeding and management and health and epidemic prevention are still to be controlled and prevents that Salmonella from entering the essential measure of food chain.Chickling goes out to drink 0.01% potassium permanganate solution after shell or other drug carries out chemoprophylaxis for 1～2 day.This bacterium produces drug resistance to common drug, forces in production, to have to carry out various medicines and be used alternatingly, in the hope of better controlling fastbacteria.This bacterium produces stronger drug resistance to aminoglycoside medicaments at present, and aminoglycoside inactive enzyme is that the necessary group of some protection antibacterial activity in these antibacterials molecules is modified, and itself and the ribosomal affinity of target site are greatly reduced.These inactive enzymes comprise aminoglycoside acyltransferase (AAC), aminoglycoside adenylyl transferase (AAD), aminoglycoside phosphotransferase (APH), gland nucleotidyltransferase (ANT) etc.In the fastbacteria of many aminoglycosides, find at present the inactive enzyme of different qualities.
Escherichia coli are common conditioned pathogens, also be normal a kind of disease of sending out, its multiple location severe infections such as chicken acute sepsis, peritonitis, hepatitis, pneumonia, enteritis of can formerly having carried out the coffin upon burial, also can secondary or mixed sending out in virosis, causes huge economic loss to aquaculture.The beta-lactam lopps antibiotic such as amoxicillin, ampicillin, ceftiofur, ceftriaxone, amoxicillin/clavulanate, ampicillin/sulbactam are the conventional important drugs of this disease of control, along with cultivation scale intensive degree is more and more large, medication is more and more spread unchecked, its Resistant strain is more and more many, also more about the report of Drug Resistance of E. coli.Studies confirm that, one of main mechanism of drug resistance is to produce beta-lactamase, especially extended spectrumβ-lactamase (Extended-Spectrum β-lactamase, ESBLs), this enzyme can be hydrolyzed beta-lactam nucleus more by force and rapidly, makes this class 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 aminoglycoside, quinolones and sulfonamides are to crossing drug resistant, only to carbapenems, a mould alkene class medicaments insensitive.Many documents reported colibacillary multi-drug resistant with produce ESBLs have substantial connection, both at home and abroad to comparatively pay close attention to.The detection, extraction, enzyme that inventor has carried out food animal source pathogenic bacterium ESBLs recently presses down the researchs such as enzyme protection effect to antibiotic percent hydrolysis and sulbactam, Tazobactam Sodium and Chinese medicine; to part ESBLs, colibacillary drug sensitive test shows, its multidrug resistant rate is apparently higher than non-ESBLs bacterial strain.In addition, result also shows to produce ESBLs bacterial strain not only to the serious drug resistance of the third generation cephalosporins such as ceftiofur, and also to multiple antimicrobial drug drug resistance such as fluoroquinolones, aminoglycoside and sulfonamides, fosfomycin etc., is serious multidrug resistant.Inventor, producing the escherichia coli that are separated to tolerate P-levels mycin product fosA3 drug resistant gene in ESBLs bacterial strain, has more strengthened 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 mortality of livestock increases, and brings larger economic loss to production, and increase poultry drug residue risk.Therefore, in actual production, need a kind of to no matter whether, the Salmonella of drug resistance and escherichia coli can have the medicine of better therapeutical effect badly, and can shorten and treat the course for the treatment of, reduce mortality rate, reduce economic loss and reduce drug residue, for raiser creates higher economic benefit, also ensure that the mankind's is healthy and safe.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of poultry compound medicine that contains Radix Paeoniae Rubra and beta-lactam antimicrobial drug, it can kill antibacterial quickly, overcome antimicrobial drug treatment due to large, the residual height of weak curative effect, consumption and the high defect of cost that drug resistance problem causes, avoided that simple Chinese medicine sterilizing spectrum is narrow, slow problem sterilizes.
For solving above technical problem, the present invention by the following technical solutions: a kind of poultry compound medicine that contains Radix Paeoniae Rubra and beta-lactam antimicrobial drug, 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 part, or ceftiofur sodium 3-25 part and Radix Paeoniae Rubra 30-190 part.
Described compound medicine is prepared into powder, tablet, oral liquid or granule.
The preparation method of described compound medicine is: Radix Paeoniae Rubra was pulverized to 60 mesh sieves, then mix with pulverous antimicrobial drug, and be prepared into according to a conventional method powder, tablet, oral liquid or granule.
For the drug resistance problem of current poultry escherichia coli and Salmonella infection existence, inventor utilizes Lactiflora and antimicrobial drug composition compound medicine.Studies have shown that, in antimicrobial drug, add after Radix Paeoniae Rubra, can reverse the drug resistance of bacteria medicine, thereby improve the therapeutic effect of antimicrobial drug.According to a conventional method this compound medicine is made to powder, tablet, oral liquid or granule, add in animal and fowl fodder and feed according to the addition of 0.1-7g principal agent/kg feedstuff, can significantly reduce drug cost and drug residue, for raiser creates higher economic benefit, also guarantee food safety simultaneously.
Detailed description of the invention
One, the drug resistance inversion effect research of Radix Paeoniae Rubra to antimicrobial drug
Antimicrobial drug itself has the effect for the treatment of escherichia coli and Salmonella, but because escherichia coli and the Salmonella of producing drug resistant gene have stronger drug resistance, causes antimicrobial drug not show good therapeutic effect in normal using dosage situation.
1, Radix Paeoniae Rubra mix with antimicrobial drug after to colibacillary drug resistance inhibition test
On 96 orifice plates, adopt microtest tube doubling dilution, first measure minimal inhibitory concentration and the subinhibitory concentration of Radix Paeoniae Rubra to product ESBLs and fosA3 drug resistant gene e. coli strains of the e. coli strains of antimicrobial drug to product ESBLs and fosA3 drug resistant gene, then in culture medium, added the Radix Paeoniae Rubra of subinhibitory concentration to reuse the minimal inhibitory concentration of microtest tube doubling dilution cultivation mensuration antimicrobial drug; Utilize continuous passage method in the culture medium that is added with same subinhibitory concentration Radix Paeoniae Rubra and same concentration antimicrobial drug to producing the cultivation of going down to posterity of ESBLs and fosA3 drug resistant gene e. coli strains, until the antimicrobial drug minimal inhibitory concentration observing diminishes more than 4 times compared with before going down to posterity, can be judged as Radix Paeoniae Rubra has drug resistance inversion effect to antibacterial medical instrument.Result of the test statistics is as shown in table 1:
Table 1 subinhibitory concentration (0.5g/mL) Radix Paeoniae Rubra goes down to posterity and causes the variation (μ g/mL) of producing ESBLs and fosA3 escherichia coli Western medicine MIC.
As seen from the above table, antimicrobial drug all reduces more than 4 times the colibacillary minimal inhibitory concentration of drug resistance, can judge that Radix Paeoniae Rubra has drug resistance inversion effect to producing ESBLs and fosA3 drug resistant gene escherichia coli.
2, Radix Paeoniae Rubra mix with antimicrobial drug after drug resistance inhibition test to Salmonella
On 96 orifice plates, adopt microtest tube doubling dilution, first measure minimal inhibitory concentration and the Radix Paeoniae Rubra subinhibitory concentration to drug resistance salmonella strain of antimicrobial drug to drug resistance salmonella strain, then in culture medium, added the Radix Paeoniae Rubra of subinhibitory concentration to reuse the minimal inhibitory concentration of microtest tube doubling dilution cultivation mensuration antimicrobial drug; Utilize continuous passage method in the culture medium that is added with same subinhibitory concentration Radix Paeoniae Rubra and same concentration antimicrobial drug to the cultivation of going down to posterity of Salmonella persister, until the antimicrobial drug minimal inhibitory concentration observing diminishes more than 4 times compared with before going down to posterity, can be judged as Radix Paeoniae Rubra has drug resistance inversion effect to antibacterial medical instrument.Result of the test statistics is as shown in table 2:
Table 2 subinhibitory concentration (0.5g/mL) Radix Paeoniae Rubra goes down to posterity and causes the variation (μ g/mL) of drug resistance Salmonella Western medicine MIC.
As seen from the above table, antimicrobial drug all reduces more than 4 times the minimal inhibitory concentration of drug resistance Salmonella, can judge that Radix Paeoniae Rubra has drug resistance inversion effect to drug resistance Salmonella.
Two, the application example of compound medicine of the present invention
Fill a prescription and following methods Preparation Example 1-embodiment 8 according to table 3: Radix Paeoniae Rubra was pulverized after 60 mesh sieves, as basic material, again with pulverous antimicrobial drug by weight ratio put into blender and mix, according to a conventional method, compound medicine is prepared into 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 |
Inventor obtains compound medicine product by above-described embodiment and has carried out following experiment:
1, the efficacy experiment of the compound medicine product of embodiment 1-4 gained 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 occur the pathological change of bag pericardium liver, typical bacillus coli feature.
Laboratory diagnosis: get pathologic liver and dye sheet, Gram’s staining, micro-Microscopic observation, the gram negative bacilli of red color visible; Tentatively be judged as bacillus coli.Cultivate by escherichia coli, biochemical test is differentiated, judges that chicken infects for bacillus coli, and pcr amplification, proves to produce the ESBLs drug resistant gene that has TEM type.
Test therapeutic regimen: morbidity chicken group is divided into 6 groups of administrations, use embodiment 1 according to the addition administration of 7g/kg feedstuff for first group, use embodiment 2 according to the addition administration of 2g/kg feedstuff for second group, use embodiment 3 according to the addition administration of 0.8g/kg feedstuff for the 3rd group, use embodiment 4 according to the addition administration of 2g/kg feedstuff for the 4th group; The 5th group with amoxicillin powder according to the addition administration of 0.2g/kg feedstuff, the 6th group with the thick powder of Radix Paeoniae Rubra according to the addition administration of 4g/kg feedstuff; Above six groups of therapeutic regimens all continue to use 5 days.
Effect feedback: after the chicken group medication of first group to the 4th group, sick chicken feed intake rises, and no longer occurs dead chicken, continues to use 3 days, and chicken group be almost recovered; The chicken group medication of the 5th group is after 2 days, and chicken group majority is still unhealthy, still has indivedual chicken deaths, continues to use 3 days, and chicken death phenomenon is not still effectively controlled; The chicken group medication of the 6th group is after 2 days, and chicken group does not have too large remarkable improvement, continues to use 3 days, and chicken death phenomenon is not still effectively controlled.Visible, the compound medicine curative effect that contains Radix Paeoniae Rubra is better than folk prescription.
2, the efficacy experiment of the meat-type duck diarrhoea of the compound medicine product of embodiment 5-8 gained to 20 ages in days
Clinical symptoms: duck field, Nanning, 20 age in days meat-type duck, duck group draws watery stools, has obvious indigested feedstuff in feces.A duck group material feeding is not but long, and the serious duck appearance foot gradually of suffering from diarrhoea is individually soft slowly dead.
Cut open inspection pathological changes: the duck that dies of illness dehydration is more serious, indivedual ducks are still very large, duck liver enlargement, hyperemia, and adularescent film on the liver of part duck, air bag muddiness, tentative diagnosis is escherichia coli or duck oromeningitis.
Test therapeutic regimen: morbidity duck group divides six groups of administrations, use embodiment 5 according to the addition administration of 3g/kg feedstuff for first group, use embodiment 6 according to the addition administration of 1.3g/kg feedstuff for second group, use embodiment 7 according to the addition administration of 0.5g/kg feedstuff for the 3rd group, use embodiment 8 according to the addition administration of 0.45g/kg feedstuff for the 4th group; The 5th group with ceftiofur sodium powder according to the addition administration of 0.2g/kg feedstuff, the 6th group with the thick powder of Radix Paeoniae Rubra according to the addition administration of 5g/kg feedstuff; Above six groups of therapeutic regimens all continue to use 5 days.
Result of use feedback: first group to the 4th group medication is after 2 days, and sick duck is no longer drawn watery stools, feces is shaped, and no longer occurs dead duck, continues to use 3 days, and duck group be almost recovered; The 5th group of medication is after 2 days, and duck group DeGrain, much still draws watery stools, contain indigested feedstuff, continue to use 3 days, some takes a turn for the better a little, but well not thoroughly, rare watery stools still occurs, use the compound medicine of embodiment 6 gained instead, continue to use 2 days, be just almost recovered, re-use 1 day, feces all transfers to normally; The 6th group of medication is after 2 days, and duck does not have too large remarkable improvement, continues to use 3 days, and the duck phenomena of mortality are not still effectively controlled.Visible, the compound medicine that contains Radix Paeoniae Rubra is better than folk prescription to the curative effect of duck diarrhoea.
3, embodiment 1-4 obtains the efficacy experiment of compound medicine product to Salmonella gallinarum disease
Clinical symptoms: Liuzhou chicken house, 13 age in days laying hens, there is dysentery in chicken group, row white, pasty state loose stool, perianal tomentum fecal pollution, has Calx sample lump, and what have sends painful shriek, has the phenomena of mortality.Cut open the indivedual Hepar Gallus domesticus enlargements of inspection and be kermesinus to darkviolet, or khaki slightly, matter is crisp easily broken, and surface is dispersed in or greyish white, the downright bad point of lark that gathers, and be red petechia sometimes, typically Salmonella genius morbi.
Laboratory diagnosis: get pathologic liver and dye sheet, Gram’s staining, micro-Microscopic observation, the gram negative bacilli of red color visible; Tentatively be judged as Salmonella disease.Cultivate by Salmonella, biochemical test is differentiated, judges that chicken infects for Salmonella disease, and 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, use embodiment 1 according to the addition administration of 7g/kg feedstuff for first group, use embodiment 2 according to the addition administration of 2g/kg feedstuff for second group, use embodiment 3 according to the addition administration of 0.8g/kg feedstuff for the 3rd group, use embodiment 4 according to the addition administration of 2g/kg feedstuff for the 4th group; The 5th group with amoxicillin powder according to the addition administration of 0.2g/kg feedstuff, the 6th group with the thick powder of Radix Paeoniae Rubra according to the addition administration of 4g/kg feedstuff; Above six groups of therapeutic regimens all continue to use 5 days.
Effect feedback: after the chicken group medication of first group to the 4th group, sick chicken feed intake rises, and no longer occurs dead chicken, continues to use 3 days, and chicken group be almost recovered; The chicken group medication of the 5th group is after 2 days, and chicken group majority is still unhealthy, still has indivedual chicken deaths, continues to use 3 days, and chicken death phenomenon is not still effectively controlled; The chicken group medication of the 6th group is after 2 days, and chicken group does not have too large remarkable improvement, continues to use 3 days, and chicken death phenomenon is not still effectively controlled.Visible, the compound medicine curative effect that contains Radix Paeoniae Rubra is better than folk prescription.
Claims (4)
1. a poultry compound medicine that contains Radix Paeoniae Rubra and beta-lactam antimicrobial drug, is characterized in that, is made up of the raw material of following weight portion: beta-lactam antimicrobial drug 3-30 part, Radix Paeoniae Rubra 5-200 part.
2. the poultry compound medicine that contains Radix Paeoniae Rubra and beta-lactam antimicrobial drug according to claim 1, is characterized in that, described beta-lactam antimicrobial drug is amoxicillin, ceftriaxone sodium or ceftiofur sodium.
3. the poultry compound medicine that contains Radix Paeoniae Rubra and beta-lactam antimicrobial drug according to claim 1, it is characterized in that, 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 ceftiofur sodium 3-25 part and Radix Paeoniae Rubra 30-190 part.
4. according to the poultry compound medicine that contains Radix Paeoniae Rubra and beta-lactam antimicrobial drug described in any one in claim 1-3, it is characterized in that, described compound medicine is prepared into powder, tablet, oral liquid or granule.
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| CN106176895A (en) * | 2016-08-22 | 2016-12-07 | 广西大学 | A kind of poultry compound medicine containing Herba Euphorbiae Humifusae and amoxicillin |
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| CN106309555A (en) * | 2016-09-21 | 2017-01-11 | 广西大学 | Composite medicine containing liquorice roots, cinnamon and ceftiofur sodium for beasts and birds |
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| CN106265880A (en) * | 2016-08-22 | 2017-01-04 | 广西大学 | A kind of poultry compound medicine containing Radix Glycyrrhizae and ceftiofur sodium |
| CN106421791A (en) * | 2016-08-29 | 2017-02-22 | 广西大学 | Compound pharmaceutical product containing desmodium triquetrum and beta-lactam antibiotics drugs for beasts and birds |
| CN106309555A (en) * | 2016-09-21 | 2017-01-11 | 广西大学 | Composite medicine containing liquorice roots, cinnamon and ceftiofur sodium for beasts and birds |
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