CN104337847A - Compound medicine containing bracken and fosfomycin for livestock - Google Patents

Compound medicine containing bracken and fosfomycin for livestock Download PDF

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Publication number
CN104337847A
CN104337847A CN201410641161.9A CN201410641161A CN104337847A CN 104337847 A CN104337847 A CN 104337847A CN 201410641161 A CN201410641161 A CN 201410641161A CN 104337847 A CN104337847 A CN 104337847A
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fosfomycin
medicine
compound medicine
group
bracken
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CN201410641161.9A
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CN104337847B (en
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刘思国
王秀梅
张万江
李兆利
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Harbin Veterinary Research Institute of CAAS
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Harbin Veterinary Research Institute of CAAS
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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
    • A61K31/66Phosphorus compounds
    • A61K31/665Phosphorus compounds having oxygen as a ring hetero atom, e.g. fosfomycin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/08Solutions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods

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

Abstract

The invention relates to a compound medicine containing bracken in pteridaceae and fosfomycin for livestock. The compound medicine is composed of the following raw materials in parts by weight: 3 to 30 parts of fosfomycin and 5 to 200 parts of bracken. According to the compound medicine, the bracken is added in the fosfomycin, so that the medicine resistance of bacteria to the fosfomycin can be reversed, thereby increasing the treatment effect of the fosfomycin. The compound medicine is prepared into powder, tablets, oral liquid or granules by using a conventional method, and is added in livestock feed according to the adding amount of 0.1 to 7 g of main medicine per kilogram of feed, so that the medicine cost and medicine residues can be greatly reduced, higher economic benefits can be created for farmers, and additionally, food safety is guaranteed.

Description

A kind of poultry compound medicine containing Herba Pteridis Multifidae and fosfomycin
Technical field
The invention belongs to poultry escherichia coli and Salmonella infection treatment technology field, particularly relate to the poultry compound medicine of a kind of Pteridaceae plant Herba Pteridis Multifidae and fosfomycin.
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 fosfomycin, 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 fosfomycin, is made up of the raw material of following weight portion: fosfomycin 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 Chinese Trsditional Medicine of Pteris Multifida Poir 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 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 1:
Table 1 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
Prepare embodiment 1-embodiment 4 according to table 2 formula and following methods: after Herba Pteridis Multifidae being pulverized 60 mesh sieves, based on raw material, then with pulverous antimicrobial drug by weight ratio put into blender and mix, compound medicine is prepared into formulation products.
The formula of table 2 embodiment 1-4 and preparation dosage form
Numbering Antimicrobial drug Herba Pteridis Multifidae Dosage form
Embodiment 1 Fosfomycin 18g 130g Powder
Embodiment 2 Fosfomycin 3g 50g Tablet
Embodiment 3 Fosfomycin 9g 10g Oral liquid
Embodiment 4 Fosfomycin 30g 170g Granule
1, the meat-type duck diarrhoea of compound medicine product to Suihua duck field 26 age in days of embodiment 1-4 gained carries out efficacy experiment.
Clinical symptoms: 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 six groups of administrations, first group with the addition administration of embodiment 1 according to 0.8g/kg feedstuff, second group with the addition administration of embodiment 2 according to 1.8g/kg feedstuff, 3rd group with the addition administration of embodiment 3 according to 0.2g/kg feedstuff, the 4th group with the addition administration of embodiment 4 according to 0.65g/kg feedstuff; 5th group with the addition administration of fosfomycin powder according to 0.1g/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.
Result of use is fed back: first group to the 4th 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; 5th 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, raiser uses the compound medicine of embodiment 1 gained instead, continue use 3 days, feces all transfers to normally; 6th 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.
2, embodiment 1-4 gained compound medicine product is to the efficacy experiment of Salmonella gallinarum disease.
Clinical symptoms: Harbin chicken house, 13 age in days laying hens, 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 1 according to 0.8g/kg feedstuff, second group with the addition administration of embodiment 2 according to 1.8g/kg feedstuff, 3rd group with the addition administration of embodiment 3 according to 0.2g/kg feedstuff, the 4th group with the addition administration of embodiment 4 according to 0.65g/kg feedstuff; 5th group with the addition administration of fosfomycin powder according to 0.1g/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 fosfomycin, it is characterized in that, be made up of the raw material of following weight portion: fosfomycin 3-30 part, Herba Pteridis Multifidae 5-200 part.
2. the poultry compound medicine containing Pteridaceae Herba Pteridis Multifidae and fosfomycin according to claim 1, it is characterized in that, described compound medicine is prepared into powder, tablet, oral liquid or granule.
CN201410641161.9A 2014-11-12 2014-11-12 A kind of livestock and poultry compound medicine containing phoenix-tail fern and phosphonomycin Expired - Fee Related CN104337847B (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106109547A (en) * 2016-08-22 2016-11-16 广西大学 A kind of poultry compound medicine containing Herba Euphorbiae Humifusae and fosfomycin
CN106166176A (en) * 2016-08-22 2016-11-30 广西大学 A kind of poultry compound medicine containing Cortex Cinnamomi and fosfomycin
CN106176910A (en) * 2016-08-22 2016-12-07 广西大学 A kind of poultry compound medicine containing Radix Glycyrrhizae and fosfomycin

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103690952A (en) * 2013-11-27 2014-04-02 广西大学 Compound drug for treating livestock and poultry escherichia coli infected diseases
CN103948656A (en) * 2014-04-25 2014-07-30 广西大学 Creat/fosfomycin-containing compound medicine for livestock and fowl
CN103989726A (en) * 2014-05-28 2014-08-20 广西大学 Acalypha australis L. and fosfomycin containing compound medicine for livestock and poultry

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103690952A (en) * 2013-11-27 2014-04-02 广西大学 Compound drug for treating livestock and poultry escherichia coli infected diseases
CN103948656A (en) * 2014-04-25 2014-07-30 广西大学 Creat/fosfomycin-containing compound medicine for livestock and fowl
CN103989726A (en) * 2014-05-28 2014-08-20 广西大学 Acalypha australis L. and fosfomycin containing compound medicine for livestock and poultry

Non-Patent Citations (1)

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Title
付声淦: "单喂"凤尾草"可防治雏鸡白痢病", 《浙江畜牧兽医》 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106109547A (en) * 2016-08-22 2016-11-16 广西大学 A kind of poultry compound medicine containing Herba Euphorbiae Humifusae and fosfomycin
CN106166176A (en) * 2016-08-22 2016-11-30 广西大学 A kind of poultry compound medicine containing Cortex Cinnamomi and fosfomycin
CN106176910A (en) * 2016-08-22 2016-12-07 广西大学 A kind of poultry compound medicine containing Radix Glycyrrhizae and fosfomycin

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