CN102462686A - Pharmaceutical composition used for preventing and treating colibacillosis in livestock and poultry - Google Patents
Pharmaceutical composition used for preventing and treating colibacillosis in livestock and poultry Download PDFInfo
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- CN102462686A CN102462686A CN2010105332876A CN201010533287A CN102462686A CN 102462686 A CN102462686 A CN 102462686A CN 2010105332876 A CN2010105332876 A CN 2010105332876A CN 201010533287 A CN201010533287 A CN 201010533287A CN 102462686 A CN102462686 A CN 102462686A
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- ceftiofur
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Abstract
The invention relates to a pharmaceutical composition used for preventing and treating colibacillosis in livestock and poultry. Every 100 g of the pharmaceutical composition comprises 2 to 10 g of ceftiofur hydrochloride, 0.25 to 10 g of tazobactam sodium, 5 to 10 g of probenecid sodium, 0.1 to 0.5 g of dexamethasone sodium phosphate and 2 to 15 g of beta-cyclodextrin, with the balance being pharmaceutically acceptable accessories. The pharmaceutical composition has the advantages of reasonable composition, low cost, a remarkable curative effect on clinical pathogenic escherichia coli, especially on drug-resistant intractable escherichia coli, a simple preparation method, stable properties and convenience in large scale intensive production.
Description
Technical field
The invention belongs to the veterinary drug field, relate in particular to a kind of pharmaceutical composition that is used to prevent and treat the poultry bacillus coli.
Background technology
Colibacillosis is the general name of one type of livestock and poultry causing of some pathogenic strains by ETEC.Escherichia coli are conditionality pathogenic bacterium, and parasitism is almost all arranged in all animal bodies, form a kind of balance in most of the time and body, when the physiological function disequilibrium of body, have pathogenic escherichia coli and the breeding advantage can occur, and cause morbidity.This disease all can take place throughout the year, and more be prone to take place season higher relatively with the Winter-Spring air humidity or climate variability, mainly causes the morbidity of poultry childhood; Mainly cause yellow scours, Hakuri, edema etc. pig; Mainly with peritonitis, perihepatitis, airsacculitis and diarrhoea are main fowl.In recent years, along with the development of poultry intensive culture industry, many important livestock and poultry pestilences are effectively controlled, and colibacillosis has the trend of obvious rising.Because e. coli serotype is more and the popular bacterial strain in various places is different, brings very big inconvenience for this sick vaccine prevention, the control to this disease is main with medicine still at present, and wherein ceftiofur has significant curative effect to primary disease.
Ceftiofur (ceftiofur) has another name called Sai Defu; It is the cephalosporins of first animal specific of the general strong company of U.S.'s Pharmacia development; Its has a broad antifungal spectrum, antibacterial activity is strong, and toxic and side effects is little; Noresidue and good pharmacokinetics process is arranged in vivo has the effect of highly significant to the control of clinical colibacillosis.But because it is water insoluble, and poor stability, often be made into ceftiofur sodium salt and ceftiofur hydrochloride to improve its stability and molten aqueous.Along with ceftiofur extensive use clinically; Escherichia coli have also produced serious drug resistance gradually to ceftiofur; It is owing to produced extended spectrum (ESBLs) that antibacterial produces chemical sproof main cause to ceftiofur; These produce the colibacillary drug resistance of ESBLs and often show as multidrug resistant; Promptly not only to the beta-lactam antibiotic drug resistance, and to non-beta-lactam antibiotic also drug resistance, the infectious disease that causes to clinical treatment product ESBLs escherichia coli causes great threat.To the at present serious drug resistance of Escherichia coli and the physicochemical property and the pharmacology characteristics of ceftiofur clinically; It is carried out reasonable combination; Produce reasonable recipe, method for preparing is simple, with low cost and is convenient to the pharmaceutical composition of clinical use, have very important production practices property.
Summary of the invention
The object of the invention is that according to present clinical Escherichia coli antibiotic being produced general serious drug resistance causes curative effect decline even invalid; The characteristics that the poultry colibacillosis is difficult to effect a radical cure; And what adopt is principal agent with the Ceftiofur Hydrochloride, cooperates other effective ingredient to carry out reasonable formula according to the physics and chemistry and the pharmacology characteristics of this medicine, thereby reaches enhancing and prolong its curative effect; Improve its stability, finally clinical drug-resistant Escherichia coli disease is reached a better prevention effect.
The technical scheme that is adopted for the present invention of realization above-mentioned purpose is following:
A kind of pharmaceutical composition that is used for preventing and treating the poultry colibacillosis: every 100g compositions contains
Ceftiofur Hydrochloride 2-10g
Sodium-tazobactam 0.25-10g
Sodium benemid 5-10g
Dexamethasone sodium phosphate 0.1-0.5g
Beta-schardinger dextrin-2-15g
Surplus is an acceptable accessories.
Said acceptable accessories comprises sucrose, oral glucose, anhydrous sodium sulfate, maltodextrin, a kind of in the soluble starch.
The antibiotic mechanism of Ceftiofur Hydrochloride is to combine with the receptor binding protein of antibacterial in the present composition; Destroy bacteria cell wall synthetic and reach efficient sterilizing idiophase effect; Its has a broad antifungal spectrum; Antibacterial activity is strong, and especially to escherichia coli, Salmonella etc. have stronger antibacterial activity; Sodium-tazobactam is another beta-lactamase inhibitor after clavulanic acid, sulbactam sodium; It presses down the enzyme effect and is superior to clavulanic acid and sulbactam sodium; Itself and ceftiofur share forms the antibacterial activity that compound preparation can strengthen ceftiofur; Can enlarge antimicrobial spectrum again, reduce untoward reaction, the caused intractable colibacillosis of clinical pathogenic product enzyme escherichia coli is had extraordinary curative effect; Sodium benemid has another name called ethamide; Be mainly used in the treatment of gout and hyperuricemia; Itself and cephalosporin share and can suppress cephalosporins and from renal tubules, drain; Thereby increase cephalosporins medicine blood drug level in vivo, delay the half-life of ceftiofur, reach strong effect and long lasting dual function; Dexamethasone sodium phosphate, not only have antitoxin, antiinflammatory, Antishock function can also be eliminated by the caused anaphylaxis of cephalosporins; Beta-schardinger dextrin-is a kind of solubilizing agent commonly used in recent years; It has hydrophobic cavity and hydrophilic outer wall; Therefore can be used as main body and Ceftiofur Hydrochloride and form clathrate, change the original physical property of medicine, playing increases its stability and deliquescent effect.Various drug synergisms; Antibacterial activity is strong; Especially the chemical sproof Escherichia coli bacterial strain of many generations is still had stronger antibacterial activity, and blood drug level is high in the poultry body, drains slowly; The blood drug level length of holding time had both reduced the curative effect that the consumption of Ceftiofur Hydrochloride has also prolonged medicine simultaneously.
A kind of pharmaceutical composition that is used to prevent and treat the poultry colibacillosis according to the invention, its preparation method are that contained each component is sieved by weight the employing conventional method, mix, and soluble powder is processed in packing.Its preparation method is simple, and character is stable, is convenient to extensive intensification and produces.
A kind of pharmaceutical composition that is used to prevent and treat the poultry colibacillosis according to the invention, its clinical application mode and usage and dosage are drinking-water administration, every 1L water use medicine 20-100mg of the present invention, logotype three days.Usage is simple, and medication is convenient, is convenient to clinical extensive intensive culture field and uses.
The invention has the beneficial effects as follows: a kind of pharmaceutical composition that is mainly used in the poultry colibacillosis that control causes by escherichia coli is provided; This medicament composing prescription is reasonable, and antibacterial activity is strong, especially the chemical sproof pathogenic drug resistance coli strain of many generations is still had very strong antibacterial activity; And blood drug level is high in the poultry body; Drain slowly, the blood drug level length of holding time had both reduced the curative effect that the drug dose of Ceftiofur Hydrochloride has also prolonged medicine simultaneously.Its preparation method is simple, and character is stable, is convenient to extensive intensification and produces.
The specific embodiment
Below in conjunction with specific embodiment technical scheme according to the invention is done further explanation.
Embodiment one
Will be through the Ceftiofur Hydrochloride 2g behind pulverizing and sieve (80 order), sodium-tazobactam 0.25g, sodium benemid 5g; Dexamethasone sodium phosphate 0.1g, beta-schardinger dextrin-2g, with sucrose to 100g; Mix homogeneously is promptly processed a kind of medicine that is mainly used in control poultry bacillus coli.
Embodiment two
Will be through the Ceftiofur Hydrochloride 5g behind pulverizing and sieve (80 order), sodium-tazobactam 1g, sodium benemid 6g; Dexamethasone sodium phosphate 0.2g, beta-schardinger dextrin-5g adds oral glucose to 100g; Mix homogeneously is promptly processed a kind of medicine that is mainly used in control poultry bacillus coli.
Embodiment three
Will be through the Ceftiofur Hydrochloride 8g behind pulverizing and sieve (80 order), sodium-tazobactam 2g, sodium benemid 8g; Dexamethasone sodium phosphate 0.3g, beta-schardinger dextrin-10g adds anhydrous sodium sulfate to 100g; Mix homogeneously is promptly processed a kind of medicine that is mainly used in control poultry bacillus coli.
Embodiment four
Will be through the Ceftiofur Hydrochloride 10g behind pulverizing and sieve (80 order), sodium-tazobactam 10g, sodium benemid 10g; Dexamethasone sodium phosphate 0.5g, beta-schardinger dextrin-15g, with soluble starch to 100g; Mix homogeneously is promptly processed a kind of medicine that is mainly used in control poultry bacillus coli.
Embodiment five: the extracorporeal bacteria inhibitor test of medicine of the present invention
1 test material
(1) clinical strains selected for use of the preparation of bacterium liquid comes from the Baoding respectively for through collaborative method of the scraps of paper and the bacterium producing multi enzyme preparation that the pcr amplification method filters out, Hengshui, and it is separating obtained that pathological material of disease is inspected in Shijiazhuang by ready samples; Reference culture is chicken source escherichia coli C
83845, pig source escherichia coli C
83907, the bacterium liquid streak inoculation that separation and purification is cultivated was cultivated 24 hours for 37 ℃ in agar plate, the single bacterium colony of picking places 10mL meat soup to cultivate 16 hours, face with before, be diluted to 10 with sterilization meat soup
5CFU/mL.
(2) preparation of medicinal liquid takes by weighing the embodiment of the invention one respectively, and embodiment two, and embodiment three; Medicine among the embodiment four and ceftiofur sodium list medicine in ceftiofur content, dilute medicine with aquesterilisa; Obtain in ceftiofur; Mass concentration finally is the medicinal liquid of 1280 μ g/mL, and all medicinal liquids are joined existing usefulness at present, prepares to be placed in 4 ℃ of refrigerators to preserve.
2 test methods
Adopt the test tube doubling dilution, measure the embodiment of the invention one respectively, embodiment two, and embodiment three, the antibacterial intensity of four pairs of escherichia coli reference cultures of embodiment and clinical product ESBLS bacterial strain.Under superclean bench, on the 96 aseptic orifice plates, the first step adds the bacterium liquid of 100 μ L from 12 holes, the 1st hole to the, and second step added the medicinal liquid of 100 μ L in the 1st hole; Mix the 1st hole with liquid-transfering gun, draw 100 μ L mixed liquors to the, 2 holes then, mix once more, pipette 100 μ L; The rest may be inferred to the 11st hole, pipettes 50 μ L, and discarding need not; Contrast is done as the contrast of bacterium liquid in the 12 hole, after mixing 1min on the micro-oscillator; Place in 37 ℃ of water isolation type electro-heating standing-temperature cultivators and cultivated 16-18 hour, take out and observe, do not see that with naked eyes the least concentration of bacterial growth is a minimum inhibitory concentration.
3 result of the tests
Ceftiofur sodium list medicine reaches and the minimal inhibitory concentration of medicine of the present invention to escherichia coli reference culture and clinical strains
Conclusion: can find out that by the extracorporeal bacteria inhibitor test result for Ji Yuan and pig source escherichia coli, the ceftiofur bacteriostatic activity is strong; Less dosage (0.2-0.4ug/mL) just can reach fungistatic effect, and for clinical separation bacterium producing multi enzyme preparation, the ceftiofur bacteriostatic activity descends; Compare with ceftiofur sodium folk prescription medicine; The present invention implements the minimal inhibitory concentration that medicine has reduced ceftiofur, has improved the antibacterial activity of ceftiofur greatly, and its antibacterial activity is 2-6 a times of folk prescription ceftiofur.
Embodiment six: the clinical efficacy test of medicine of the present invention
1 test material
(1) experimental animal is 1 age in days Luo Man egg chick, in identical temperature, and humidity, the illumination condition interior isolation of house was down raised in cages 7 days, and feeding does not contain antibiotic complete feed fully, freely drinks water, need not any medicine or vaccine immunity.
(2) test strain is that the enzyme escherichia coli are produced in the clinical separation of the sick chicken of area, Shijiazhuang censorship, faces with before getting cryopreserved chicken colibacillosis bacterium liquid, is inoculated in nutrient broth and cultivates 16～18 hours; On the Mai Kangkai flat board streak culture 24 hours, the single colony inoculation of picking aubergine was cultivated 18 hours in nutrient broth, was inoculated in 1 Japanese instar chickling through lumbar injection 1mL; It is depressed that spirit appears in back to the sick chicken that spends the night, and has loose bowels clinical symptoms such as death; Cut open the sick chicken of inspection separating Escherichia coli from liver and be inoculated in Mai Kangkai culture medium cultivation 24 hours; The single bacterium colony of picking was cultivated 12～16 hours in 10mL sterilization meat soup, preserved subsequent use in 4 ℃ of refrigerators.
(3) trial drug is selected medicine and the commercially available ceftiofur sodium powder pin that the embodiment of the invention one is prepared, and (10%) three kind of medicine of commercially available amoxicillin soluble powder is treated respectively.Three kinds of drug administration dosage are all in effective ingredient, every 1L water administration 25mg, logotype three days.
2 test methods
With 120 7 age in days Luo Man egg chicks, be divided into 4 groups at random, 30 every group before the test; Infect the matched group chickling and infect not administration, all the other respectively organize chickling lumbar injection 0.4mL bacterium liquid, and the artificial challenge is after 8 hours; It is thus clear that it is depressed that spirit appears in chickling, draws the yellow-white loose stool, degradation clinical symptoms under the appetite; To the administration of drinking water of each treatment group, every day 2 times, continuous use 3 days.Duration of test is raised by normal mode, the mental status of observing chickling every day, and the appetite situation, the feces situation writes down the death toll of disease chicken, cuts open inspection and observes pathological changes, can do the antibacterial separation and Culture in case of necessity and identify.From the on-test to the off-test, observed 7 days continuously.After experiment finishes, all at duration of test, after the medication treatment, spirit, appetite, situation such as feces recover to be judged as normally healing, and the ratio that accounts for this group test chicken number according to the quantity of curing chicken is calculated cure rate; All at duration of test, escherichia coli classical symptom and pathological change appear, and separation and Culture goes out colibacillary confirming as and infects and dead, accounts for the ratio calculating mortality rate of this group test chicken number according to each quantity of organizing dead chicken.
3 result of the tests
The a pair of artificial challenge chickling of the embodiment of the invention produces the colibacillary clinical trial result of enzyme
Conclusion: can know by experimental result; Pharmaceutical composition of the present invention has tangible prevention and therapeutic effect to clinical escherichia coli; Especially amoxicillin etc. has been produced chemical sproof clinical product enzymic characteristic of disease escherichia coli curative effect has preferably been arranged; Compare with single ceftiofur sodium, improved the antibacterial activity of ceftiofur greatly.
Claims (3)
1. pharmaceutical composition that is used to prevent and treat the poultry colibacillosis, it is characterized in that: said pharmaceutical composition comprises Ceftiofur Hydrochloride, sodium-tazobactam, sodium benemid, dexamethasone sodium phosphate, beta-schardinger dextrin-and acceptable accessories.
2. a kind of pharmaceutical composition that is used to prevent and treat the poultry colibacillosis according to claim 1; It is characterized in that hydrochloric ceftiofur 2-10g in every 100g pharmaceutical composition of the present invention; Sodium-tazobactam 0.25-10g, sodium benemid 5-10g, dexamethasone sodium phosphate 0.1-0.5g; Beta-schardinger dextrin-2-15g, surplus is an acceptable accessories.
3. a kind of pharmaceutical composition that is used to prevent and treat the poultry colibacillosis according to claim 1 and 2, it is characterized in that: said acceptable accessories is selected from sucrose, oral glucose, anhydrous sodium sulfate, maltodextrin, a kind of in the soluble starch.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105332876A CN102462686A (en) | 2010-11-05 | 2010-11-05 | Pharmaceutical composition used for preventing and treating colibacillosis in livestock and poultry |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105332876A CN102462686A (en) | 2010-11-05 | 2010-11-05 | Pharmaceutical composition used for preventing and treating colibacillosis in livestock and poultry |
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| CN102462686A true CN102462686A (en) | 2012-05-23 |
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| CN2010105332876A Pending CN102462686A (en) | 2010-11-05 | 2010-11-05 | Pharmaceutical composition used for preventing and treating colibacillosis in livestock and poultry |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103230364A (en) * | 2013-05-13 | 2013-08-07 | 青岛农业大学 | Preparation method of ceftiofur acid long-acting injection |
| CN103751196A (en) * | 2014-01-08 | 2014-04-30 | 中国农业科学院兰州畜牧与兽药研究所 | Ceftiofur hydroxypropyl-beta-cyclodextrin inclusion compound and preparation method thereof |
-
2010
- 2010-11-05 CN CN2010105332876A patent/CN102462686A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103230364A (en) * | 2013-05-13 | 2013-08-07 | 青岛农业大学 | Preparation method of ceftiofur acid long-acting injection |
| CN103751196A (en) * | 2014-01-08 | 2014-04-30 | 中国农业科学院兰州畜牧与兽药研究所 | Ceftiofur hydroxypropyl-beta-cyclodextrin inclusion compound and preparation method thereof |
| CN103751196B (en) * | 2014-01-08 | 2016-08-17 | 中国农业科学院兰州畜牧与兽药研究所 | Ceftiofur hydroxypropyl-beta-cyclodextrin inclusion and preparation method thereof |
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Application publication date: 20120523 |