CN104435013A - Pteris multifida and amikacin-containing compound drug for livestock and poultry - Google Patents

Pteris multifida and amikacin-containing compound drug for livestock and poultry Download PDF

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Publication number
CN104435013A
CN104435013A CN201410636215.2A CN201410636215A CN104435013A CN 104435013 A CN104435013 A CN 104435013A CN 201410636215 A CN201410636215 A CN 201410636215A CN 104435013 A CN104435013 A CN 104435013A
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amikacin
drug
group
poultry
herba pteridis
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孙坚
崔泽华
单体江
司红彬
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South China Agricultural University
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South China Agricultural University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/11Pteridophyta or Filicophyta (ferns)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/7036Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Medical Informatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

The invention relates to a pteris multifida and amikacin-containing compound drug for livestock and poultry. The pteris multifida and amikacin-containing compound drug is composed of the following raw materials in parts by weight: 3-30 parts of amikacin and 5-200 parts of pteris multifida. After the pteris multifida is added into the amikacin, the drug resistance of bacteria to the amikacin can be reversed, so that the treatment effect of the amikacin is improved. The compound drug is prepared into powder, tablets, an oral solution or granules according to a conventional method and is fed to livestock and poultry after being added into a feed for livestock and poultry according to the dosage that 0.1-7g of a main drug is added in every kilogram of the feed, so that the medication cost and drug residues can be greatly reduced, a higher economic benefit is created for a farmer, and meanwhile, the food safety is ensured.

Description

A kind of poultry compound medicine containing Herba Pteridis Multifidae and amikacin
Technical field
The invention belongs to poultry escherichia coli and Salmonella infection treatment technology field, particularly relate to a kind of poultry compound medicine containing Pteridaceae plant Herba Pteridis Multifidae and amikacin.
Background technology
Fowl salmonellosis (Avian salmonellosis) is the general name of the poultry disease caused by one or more Salmonellas in Salmonella.Difference according to pathogen antigen structure can be divided into 3 classes: 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 then can extensively infect many animals and people, is one of main source of mankind's Salmonella infection and alimentary toxicosis by poultry that it pollutes and products thereof.Fowl salmonellosis often forms quite complicated propagation circulation.Sick fowl and the fowl that carries disease germs are the main sources of infection, by digestive tract, respiratory tract or eye conjunctiva horizontal transmission, poult can be infected after ovum vertical transmission, cause major part dead, poultry carries disease germs for a long time, then the ovum that carries disease germs of output, if hatch in this, as hatching egg, that then can go round and begin again is handed down from age to age, and causes fowl salmonellosis to be difficult to purification in chicken group, causes serious economic loss.Because Salmonella pollutes face greatly in chicken group, and easily produce drug resistance, immune effect of vaccine is in the market all undesirable.Therefore, breeder flock quarantine, medicine control, environment disinfected purifies, strengthen feeding and management and health and epidemic prevention is still control and prevents Salmonella from entering the essential measure of food chain.Chickling drinks 0.01% potassium permanganate solution after going out shell or other drug carries out chemoprophylaxis in 1 ~ 2 day.This bacterium produces drug resistance to common drug, forces in production to have to carry out various medicine 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 modifies the necessary group of some protection antibacterial activity in these antibacterials molecules, 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 the inactive enzyme of different qualities at present.
Escherichia coli are common conditioned pathogens, also be the normal a kind of disease sent out, it can formerly have been carried out the coffin upon burial the multiple location severe infections such as chicken acute sepsis, peritonitis, hepatitis, pneumonia, enteritis, also can secondary or mixedly to send 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, and the report about Drug Resistance of E. coli is also more.Research confirms, one of main mechanism of drug resistance produces 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 kind of antibiotic lose antibacterial activity.ESBLs is the main enzyme type of beta-lactamase, and it not only to cephalo three generations and aztreonam drug resistance, and is crossing drug resistant to aminoglycoside, quinolones and sulfonamides, 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.Inventor has carried out the detection of food animal source pathogenic bacterium ESBLs recently, extraction, enzyme press down the researchs such as enzyme protection effect to antibiotic percent hydrolysis and sulbactam, Tazobactam Sodium and Chinese medicine; show the colibacillary drug sensitive test of part ESBLs, 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., in serious multidrug resistant.Inventor is separated to the escherichia coli of resistance to fosfomycin product fosA3 drug resistant gene producing in ESBLs bacterial strain, more strengthen 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, and increase poultry drug residue risk to production.Therefore, the medicine that a kind of Salmonella of the drug resistance to no matter whether and escherichia coli can have better therapeutical effect is needed badly in actual production, and can shorten treatment 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 containing Pteridaceae Herba Pteridis Multifidae and amikacin, it can kill antibacterial quickly, overcome large, the residual high and defect that cost is high of weak curative effect that antimicrobial drug treatment causes due to drug resistance problems, consumption, avoid that 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 poultry compound medicine containing Pteridaceae Herba Pteridis Multifidae and amikacin, is made up of the raw material of following weight portion: amikacin 3-30 part, Herba Pteridis Multifidae 5-200 part.
Described compound medicine is prepared into powder, tablet, oral liquid or granule.
The preparation method of described compound medicine is: Herba Pteridis Multifidae was pulverized 60 mesh sieves, then mixes with pulverous antimicrobial drug, is prepared into powder, tablet, oral liquid or granule according to a conventional method.
For the drug resistance problems that current poultry escherichia coli and Salmonella infection exist, inventor utilizes Herba Pteridis Multifidae and antimicrobial drug to form compound medicine.Research proves, after adding Herba Pteridis Multifidae in antimicrobial drug, can reverse bacterial to the drug resistance of 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 0.1-7g principal agent/addition of kg feedstuff and feed, can significantly reduce drug cost and drug residue, for raiser creates higher economic benefit, also ensure that food safety simultaneously.
Detailed description of the invention
One, Herba Pteridis Multifidae is to the drug resistance inversion Effect study of antimicrobial drug
Antimicrobial drug itself has treatment escherichia coli and the effect of Salmonella, but has stronger drug resistance due to the escherichia coli and Salmonella producing drug resistant gene, causes antimicrobial drug not show good therapeutic effect in normal using dosage situation.
1, Herba Pteridis Multifidae mix with antimicrobial drug after to colibacillary drug resistance inhibition test
96 orifice plates adopt microtest tube doubling dilution, first determine antimicrobial drug to producing the minimal inhibitory concentration of e. coli strains of ESBLs and fosA3 drug resistant gene and Herba Pteridis Multifidae to the subinhibitory concentration producing ESBLs and fosA3 drug resistant gene e. coli strains, the Herba Pteridis Multifidae then adding subinhibitory concentration in the medium reuses microtest tube doubling dilution and cultivates the minimal inhibitory concentration measuring antimicrobial drug; Continuous passage method is utilized to carry out Secondary Culture to product ESBLs and fosA3 drug resistant gene e. coli strains in the culture medium being added with same subinhibitory concentration Herba Pteridis Multifidae and same concentration antimicrobial drug, until the antimicrobial drug minimal inhibitory concentration observed diminishes more than 4 times compared with before going down to posterity, can be judged as that Herba Pteridis Multifidae 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) Herba Pteridis Multifidae is gone down to posterity and causes the change (μ g/mL) of product ESBLs and fosA3 escherichia coli Western medicine MIC.
As seen from the above table, antimicrobial drug all reduces more than 4 times to the minimal inhibitory concentration of antibiotic-resistance E. coli, can judge that Herba Pteridis Multifidae has drug resistance inversion effect to product ESBLs and fosA3 drug resistant gene escherichia coli.
2, Herba Pteridis Multifidae mix with antimicrobial drug after drug resistance inhibition test to Salmonella
96 orifice plates adopt microtest tube doubling dilution, first determine antimicrobial drug to the minimal inhibitory concentration of drug resistance salmonella strain and Herba Pteridis Multifidae to the subinhibitory concentration of drug resistance salmonella strain, the Herba Pteridis Multifidae then adding subinhibitory concentration in the medium reuses microtest tube doubling dilution and cultivates the minimal inhibitory concentration measuring antimicrobial drug; Continuous passage method is utilized to carry out Secondary Culture to Salmonella persister in the culture medium being added with same subinhibitory concentration Herba Pteridis Multifidae and same concentration antimicrobial drug, until the antimicrobial drug minimal inhibitory concentration observed diminishes more than 4 times compared with before going down to posterity, can be judged as that Herba Pteridis Multifidae 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) Herba Pteridis Multifidae is gone down to posterity 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, can judge that Herba Pteridis Multifidae has drug resistance inversion effect to drug resistance Salmonella.
Two, the application example of compound medicine of the present invention
Embodiment 1-embodiment 10 is prepared: after Herba Pteridis Multifidae being pulverized 60 mesh sieves according to table 3 formula and following methods, based on raw 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 1-10 and preparation dosage form
Numbering Antimicrobial drug Herba Pteridis Multifidae Dosage form
Embodiment 1 Amikacin 20g 80g Powder
Embodiment 2 Amikacin 13g 10g Tablet
Embodiment 3 Amikacin 7g 160g Oral liquid
Embodiment 4 Amikacin 30g 110g Granule
Embodiment 5 Amikacin 15g 120g Powder
Embodiment 6 Amikacin 25g 50g Tablet
Embodiment 7 Amikacin 10g 80g Oral liquid
Embodiment 8 Amikacin 30g 160g Granule
Embodiment 9 Amikacin 3g 5g Powder
Embodiment 10 Amikacin 30g 200g Tablet
Above-described embodiment is obtained compound medicine product and has carried out following experiment by inventor:
1, the compound medicine product of embodiment 1-4 gained is to the efficacy experiment of the piglet diarrhea of 38 ages in days
Clinical symptoms: pig farm, Guangzhou, 38 age in days piglets, this swinery, after wean is turn-taked, starts to occur diarrhoea, draws watery stools, feces contains indigested feedstuff, pig material feeding but be exactly not long, diarrhea of pigs dehydration serious is individually dead, does not occur symptoms of emesis, raiser uses multi-medicament, and treatment does not all occur ideal effect.
Cut open inspection pathological changes: after cuing open inspection, Intestinum Sus domestica wall is belittled, especially small intestinal rear end and colon site, and intestinal mucosa comes off, and intestinal wall is congested, hemorrhage.
Laboratory diagnosis: get pathologic liver dye sheet, Gram’s staining, basis of microscopic observation, the gram negative bacilli of red color visible; Tentatively be judged as bacillus coli.Cultivated by escherichia coli, biochemical test is differentiated, judges that Infection in Piglets is bacillus coli, pcr amplification, proves to produce the ESBLs drug resistant gene and the fosA3 drug resistant gene that there are CTX-M type.
Test therapeutic regimen: morbidity swinery divides 6 groups of administrations, first group with the addition administration of embodiment 1 according to 1.5g/kg feedstuff, second group with the addition administration of embodiment 2 according to 0.5g/kg feedstuff, 3rd group with the addition administration of embodiment 3 according to 7g/kg feedstuff, the 4th group with the addition administration of embodiment 4 according to 1.3g/kg feedstuff; 5th group with the addition administration of amikacin powder according to 0.3g/kg feedstuff, the 6th group with the addition administration of the thick powder of Herba Pteridis Multifidae according to 7g/kg feedstuff; Above six groups of therapeutic regimens all continue use 5 days.
Result of use is fed back: first group to the 4th group medication is after 2 days, and swinery no longer draws watery stools, formed stools, and no longer containing feedstuff in feces, continue use 3 days, swinery is fully recovered; 5th group of medication is after 2 days, and swinery is still unhealthy, continues use 3 days, substantially get well, but still draw pasty state feces individually, but drug withdrawal is after 3 days, and recurrence appears in swinery; 6th group of medication is after 2 days, and swinery is without remarkable improvement, and continue use 3 days, swinery continues to have loose bowels, and all the other are also more serious individually.Visible, the compound medicine containing Herba Pteridis Multifidae is better than folk prescription amikacin and folk prescription Herba Pteridis Multifidae to swinery curative effect.
2, the compound medicine product of embodiment 5-10 gained efficacy experiment that the meat-type duck of 28 ages in days is suffered from diarrhoea
Clinical symptoms: duck field, Guangzhou, 28 age in days meat-type duck, duck group draws watery stools, has obvious indigested feedstuff in feces.The duck appearance foot gradually that indivedual diarrhoea is serious is soft slowly dead.
Cut open inspection pathological changes: the duck that dies of illness dehydration is relatively more serious, indivedual duck is still very large, duck liver enlargement, hyperemia, and adularescent film on the liver of part duck, air bag is muddy, and tentative diagnosis is escherichia coli or duck oromeningitis.
Test therapeutic regimen: morbidity duck group divides 8 groups of administrations, first group with the addition administration of embodiment 5 according to 2.5g/kg feedstuff, second group with the addition administration of embodiment 6 according to 0.9g/kg feedstuff, 3rd group with the addition administration of embodiment 7 according to 2.5g/kg feedstuff, the 4th group with the addition administration of embodiment 8 according to 1.7g/kg feedstuff; 5th group with the addition administration of embodiment 9 according to 0.8g/kg feedstuff, the 6th group with the addition administration of embodiment 10 according to 2.3g/kg feedstuff; 7th group with the addition administration of amikacin powder according to 0.3g/kg feedstuff, the 8th group with the addition administration of the thick powder of Herba Pteridis Multifidae according to 4g/kg feedstuff; Above eight groups of therapeutic regimens all continue use 5 days.
Result of use is fed back: first group to the 6th group medication is after 3 days, and sick duck no longer draws watery stools, formed stools, no longer occurs dead duck, and continue use 2 days, duck group be almost recovered; 7th group of medication is after 3 days, duck group DeGrain, much still draw watery stools, containing indigested feedstuff, continue use 2 days, some takes a turn for the better a little, but not good thorough, rare watery stools still occurs, uses the compound medicine of embodiment 5 gained instead, continue use 3 days, feces all transfers to normally; 8th group of medication is after 3 days, and duck does not have too large remarkable improvement, and continue use 2 days, the duck phenomena of mortality are not still effectively controlled.Visible, the compound medicine containing Herba Pteridis Multifidae is better than folk prescription to the curative effect that duck is suffered from diarrhoea.
3, embodiment 5-8 gained compound medicine product is to the efficacy experiment of Salmonella gallinarum disease
Clinical symptoms: Guangzhou chicken house, 13 Day-old Broiler Chickens, there is dysentery in chicken group, row's white, pasty state loose stool, and 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 enlargement of inspection be kermesinus to darkviolet, or slightly khaki, matter is crisp easily broken, and surface is dispersed in or greyish white, the downright bad point of lark that gathers, and is the petechia of redness sometimes, typical Salmonella genius morbi.
Laboratory diagnosis: get pathologic liver dye sheet, Gram’s staining, basis of microscopic observation, the gram negative bacilli of red color visible; Tentatively be judged as Salmonella disease.Cultivated by Salmonella, biochemical test is differentiated, judge that chicken infects as 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 with the addition administration of embodiment 5 according to 2.5g/kg feedstuff, second group with the addition administration of embodiment 6 according to 0.9g/kg feedstuff, 3rd group with the addition administration of embodiment 7 according to 2.5g/kg feedstuff, the 4th group with the addition administration of embodiment 8 according to 1.7g/kg feedstuff; 5th group with the addition administration of amikacin powder according to 0.3g/kg feedstuff, the 6th group with the addition administration of the thick powder of Herba Pteridis Multifidae according to 4g/kg feedstuff; Above six groups of therapeutic regimens all continue use 5 days.
Staining effect: after the chicken group medication of first group to the 4th group, sick chicken feed intake rises, and no longer occurs dead chicken, and continue use 3 days, 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 death, and continue use 3 days, 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, and continue use 3 days, chicken death phenomenon is not still effectively controlled.Visible, the compound medicine curative effect containing Herba Pteridis Multifidae is better than folk prescription.

Claims (2)

1. contain a poultry compound medicine for Pteridaceae Herba Pteridis Multifidae and amikacin, it is characterized in that, be made up of the raw material of following weight portion: amikacin 3-30 part, Herba Pteridis Multifidae 5-200 part.
2. the poultry compound medicine containing Pteridaceae Herba Pteridis Multifidae and amikacin according to claim 1, it is characterized in that, described compound medicine is prepared into powder, tablet, oral liquid or granule.
CN201410636215.2A 2014-11-12 2014-11-12 Pteris multifida and amikacin-containing compound drug for livestock and poultry Pending CN104435013A (en)

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Publication number Priority date Publication date Assignee Title
CN106176896A (en) * 2016-08-22 2016-12-07 广西大学 A kind of poultry compound medicine containing Herba Euphorbiae Humifusae and amikacin
CN106420893A (en) * 2016-08-29 2017-02-22 广西大学 Tadehagi triquetrum and amikacin containing compound medicine for livestock and poultry

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106176896A (en) * 2016-08-22 2016-12-07 广西大学 A kind of poultry compound medicine containing Herba Euphorbiae Humifusae and amikacin
CN106420893A (en) * 2016-08-29 2017-02-22 广西大学 Tadehagi triquetrum and amikacin containing compound medicine for livestock and poultry

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Application publication date: 20150325