CN104971124B - A kind of new application of pharmaceutical composition - Google Patents
A kind of new application of pharmaceutical composition Download PDFInfo
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- CN104971124B CN104971124B CN201410142650.XA CN201410142650A CN104971124B CN 104971124 B CN104971124 B CN 104971124B CN 201410142650 A CN201410142650 A CN 201410142650A CN 104971124 B CN104971124 B CN 104971124B
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The present invention provides the purposes of pharmaceutical composition as described below in the drug of preparation prevention or treatment birds salmonellosis；Described pharmaceutical composition is the preparation being prepared by the bulk pharmaceutical chemicals of following weight proportion: 150-200 parts of radix scutellariae, 150-200 parts of Fructus Forsythiae, 150-200 parts of radix paeoniae rubra, 50-100 parts of the coptis, 250-350 parts of Cortex Phellodendri, 50-100 parts of Radix Glycyrrhizae.The research of the invention finds that, after the 6 taste medicine compatibility such as radix scutellariae, it can effectively prevent or treat the effect of birds salmonellosis, especially for Salmonella pullorum disease significant effect, it is suitable with positive drug effects of antibiotics, use of the alternative antibiotic in such disease provides possibility to avoid generating drug-fast bacteria.
Description
Technical field
The present invention relates to a kind of new applications of pharmaceutical composition.
Background technique
Salmonella is an important Pseudomonas in enterobacteriaceae, is widely present in nature, is in direct rod shape, no bud
Spore, Gram-negative.Salmonella in 1885 etc. is separated to Salmonella choleraesuls in Cholera Epidemic, therefore names as salmonella
Belong to.Salmonella has 2500 kinds or more of serotype, other than the serotype rare less than 10 belongs to Bang Geer salmonella,
Remaining serotype belongs to Salmonella enteritidis.Mainly there are Bacterium enteritidis, salmonella typhimurium, hog cholera Salmonella
Bacterium, S. pullonum, avian infectious bronchitis nephritis virus etc..It can cause a plurality of types of diseases, and and people to humans and animals
Class health, animal husbandry and the development relationship of international trade are close.
Salmonella pullon (Salmonella pullorum) is that Rettger divided from dysentery characterized by white mucous stool diseased chicken in 1899
From arriving.The white diarrhea as caused by it (Pullorum disease) is one of the poultry diease being found earliest.And the disease is confirmed to be
It is egg matchmaker's property disease.White diarrhea disease disease incidence is high, and chick is in break out more, and case fatality rate is high；Adult Chicken is in subclinical infection or chronic more
Infection, though without obvious clinical symptoms, caused by economic loss it is still very big.Therefore, anti-this disease of system is especially supported to intensive
The control of the chicken house disease is always the hot issue studied at present.Wherein drug controls the disease and is most effective and most common arranges
One of apply.However, the long-time service of single variety can induce Salmonella bar due to antibiotic and the irrational use of antimicrobial
Bacterium generates drug resistance, and the effect of common drug is more and more undesirable.Therefore effective preparation is researched and developed to control the disease and seem special
It is unimportant.
Summary of the invention
The purpose of the present invention is to provide a kind of new applications of pharmaceutical composition.
The present invention provides pharmaceutical compositions as described below in preparation prevention or the drug for the treatment of birds salmonellosis
In purposes；Described pharmaceutical composition is the preparation being prepared by the bulk pharmaceutical chemicals of following weight proportion:
150-200 parts of radix scutellariae, 150-200 parts of Fructus Forsythiae, 150-200 parts of radix paeoniae rubra, 50-100 parts of the coptis, 250-350 parts of Cortex Phellodendri,
50-100 parts of Radix Glycyrrhizae.
Further, the birds are chicken, duck or goose.
Further, the drug is the drug of prevention or treatment Salmonella pullorum disease.
Further, the drug is the drug of prevention or treatment Salmonella pullorum disease.
Further, it is the veterinary drug preparation being prepared by the bulk pharmaceutical chemicals of following weight proportion:
185 parts of radix scutellariae, 185 parts of Fructus Forsythiae, 185 parts of radix paeoniae rubra, 74 parts of the coptis, 297 parts of Cortex Phellodendri, 74 parts of Radix Glycyrrhizae.
Wherein, the drug is with the extraction of the water or organic solvent of the medicinal powder of the weight proportion bulk pharmaceutical chemicals or bulk pharmaceutical chemicals
Object is active constituent, in addition the preparation that pharmaceutically common auxiliary material or complementary ingredient are prepared.
By verification experimental verification, the powder that the medicinal powder of the present composition is directly prepared can effectively prevent or treat chicken
Salmonella pullorum disease can extract medicinal material to adapt to different requirements or reduce product dose, is pure
Change, has veterinary drug preparation of different nature in order to reduce dose or be made.
The veterinary drug preparation may be, but not limited to, injection, solution, decoction, preserved material, mixture, emulsion, aqua, leaching
Paste, eclegm, pulvis, pre-mixing agent, tablet, pill, capsule, microcapsules, granule, oral solution etc..
The research of the invention finds that have the function of preventing and treating birds salmonellosis after the 6 taste medicine compatibility such as radix scutellariae,
Suitable with positive drug effects of antibiotics especially for Salmonella pullorum disease significant effect, alternative antibiotic is at this
Use in class disease provides possibility to avoid generating drug-fast bacteria.
Detailed description of the invention
Result (HE was observed by the histopathologic slide after dissect in Fig. 1 healthy control group chick the 6th day；200 ×/400 ×):
A: cardiac muscle fibre arrangement is close, and core occupies center, the internal membrane of heart and external membrane of heart structural integrity.
B: liver lobuli hepatis structure is clear, and for central vein without extravasated blood, liver plate is radial, and sinus hepaticus is without expansion and oedema.
C: splenic capsule is complete, spleen trabeculae as it can be seen that acini lienalis negligible amounts, central artery sheath without hyperemia, in red pulp snius lienis without
Expansion, desmacyte is without hyperplasia.
D: for bronchuses at different levels as it can be seen that peribronchial only has individually a little cell infiltration, alveolar size is similar, interstitial without
Bleeding extravasated blood and fibrosis.
E: caecum wall construction is complete, it is seen that villus and crypts have no cell infiltration under mucosal erosion, mucous membrane.
F: caecum fluff structures are complete, it is seen that structural integrity crypts has no that obvious mucous epithelium falls off, and length is normal.
Fig. 2 infects the histopathologic slide observation result (HE after control group death chick dissect；200 ×/400 ×):
A: cardiac muscle fibre is disorganized, and core, which occupies, to disappear, Myocardial fibroklasts cavity.Show myocardium cell necrosis.And the visible heart
Extravasated blood.
B: liver lobuli hepatis structure is unintelligible, portal area cell infiltration, the radial disappearance of liver plate.
C: splenic capsule falls off, envelope necrosis.Cell infiltration.
D: brochial mucosa bleeding, cell infiltration.
E: caecum wall falls off with mucous membrane, and villus shortens, and crypts becomes smaller, and placenta percreta falls off necrosis.
F: caecum villus shortens, and crypts is reduced, it is seen that obvious mucous epithelium falls off.
Fig. 3 middle dosage intestines bacterium dissipates clearly group and dies of illness the observation result (HE of the histopathologic slide after chick dissect；200×/400
×):
A: cardiac muscle fibre arrangement is more neat, and part cavity occurs in endomyocardial side fibrocyte.Show myocardium cell necrosis.But
It is light compared with infection control group.
B: liver envelope structural integrity.Hepatic region cell is clear.
C: acini lienalis structure is substantially complete, has no obvious lesion tissue.
D: it is relatively cleaned in lung tissue bronchus, it is seen that lung tissue interstitial hemorrhage, cell infiltration.But it is bright compared with infection control group
It is aobvious slight.
E: caecum wall and envelope structural integrity, but see that caecum villus shortens compared with healthy control group, crypts becomes smaller, placenta percreta group
It knits and sees a small amount of slough tissue.It is obviously slight compared with infection control group.
Fig. 4 high dose intestines bacterium dissipates clearly group and dies of illness the observation result (HE of the histopathologic slide after chick dissect；200×/400
×):
A: cardiac muscle fibre arrangement is more neat, there is cell infiltration between cardiac muscle cell.But relatively infection control group is light.
B: liver envelope structural integrity.Hepatic region cell is clear.But central vein extravasated blood.
C: diagram liver plate is radial substantially complete, but sees liver cell nonresident portion steatosis.
D: acini lienalis structure is substantially complete, has no obvious lesion tissue.
E: cleaning in lung tissue bronchus, but visible bronchial tissue part consolidation.There is inflammation mistake suspected of preinfection
Repairing phase after journey.
F: caecum wall and envelope structural integrity, but see that caecum villus shortens compared with healthy control group, crypts becomes smaller, placenta percreta group
It knits and sees a small amount of slough tissue.It is obviously slight compared with infection control group.
Fig. 5 positive drug control group prevention group is died of illness the observation result (HE of the histopathologic slide after chick dissect；200×/
400 ×):
A: myocardium Non Apparent Abnormality.
B: liver cell structural integrity, portal area cell infiltration.
C: diagram liver plate is radial substantially complete, but sees that sinus hepaticus is expanded.
D: acini lienalis structure is substantially complete, has no obvious lesion tissue.
E: cleaning in lung tissue bronchus, but visible terminal bronchial tissue inner part bleeding and cell infiltration.Suspected of
There is the repairing phase after inflammatory process in infection.
F: caecum wall and envelope structural integrity, but see that caecum villus is elongated compared with healthy control group.Crypt depth deepens.
Fig. 6 diagram positive drug control group treatment group dies of illness the observation result (HE of the histopathologic slide after chick dissect；
200 ×/400 ×):
A: the obvious cell infiltration of cardiac muscular tissue.
B: part hepatic tissue hydropic degeneration.
C: bleeding around diagram lung tissue blood vessel.
D: lung tissue structure is substantially complete, and cleaning, without obvious bleeding and rheuminess object, has no obvious group in bronchial lumen
Knit lesion.
E: caecum envelope structural integrity, but see that caecum villus is elongated compared with healthy control group.Crypt depth deepens.
Specific embodiment
The preparation of the pharmaceutical composition of the present invention of embodiment 1
Radix scutellariae 185g, Fructus Forsythiae 185g, radix paeoniae rubra 185g, coptis 74g, Cortex Phellodendri 297g, Radix Glycyrrhizae 74g are taken, after crushing, mixes, does
It is dry to get powder.
The preparation of the pharmaceutical composition of the present invention of embodiment 2
Radix scutellariae 200g, Fructus Forsythiae 150g, radix paeoniae rubra 160g, coptis 50g, Cortex Phellodendri 250g, Radix Glycyrrhizae 50g are taken, after crushing, is mixed, then
Appropriate suspending agent is added, prepares suspension.
The preparation of the pharmaceutical composition of the present invention of embodiment 3
Radix scutellariae 150g, Fructus Forsythiae 200g, radix paeoniae rubra 200g, coptis 100g, Cortex Phellodendri 350g, Radix Glycyrrhizae 100g are taken, is added water to cook 3 times,
After concentration, appropriate filler is added, prepares granule.
The preparation of the pharmaceutical composition of the present invention of embodiment 4
Radix scutellariae 160g, Fructus Forsythiae 160g, radix paeoniae rubra 160g, coptis 90g, Cortex Phellodendri 330g, Radix Glycyrrhizae 90g are taken, 95% ethyl alcohol is added to extract 2
It is secondary, merge alcohol extract, the dregs of a decoction add water to cook 2 times, merge decocting liquid；After alcohol extract is recycled ethyl alcohol, merge with decocting liquid, it is spraying
It is dry, appropriate suspending agent is added, prepares suspension.
The preparation of the pharmaceutical composition of the present invention of embodiment 5
Radix scutellariae 190g, Fructus Forsythiae 190g, radix paeoniae rubra 190g, coptis 60g, Cortex Phellodendri 280g, Radix Glycyrrhizae 60g are taken, 60-65% ethyl alcohol is added to mention
It takes 3 times, merges alcohol extract, after recycling ethyl alcohol, spray drying is added appropriate amount of auxiliary materials, prepares granule.
The preparation of the pharmaceutical composition of the present invention of embodiment 6
Radix scutellariae 185g, Fructus Forsythiae 185g, radix paeoniae rubra 185g, coptis 74g, Cortex Phellodendri 297g, Radix Glycyrrhizae 74g are taken, is added water to cook 3 times, is closed
And decocting liquid, it is concentrated, stands, appropriate corrigent and bacteriostatic agent is added in filtration, filtrate, is prepared into oral solution.
Beneficial effects of the present invention are illustrated below by way of test example.
The therapeutic effect of 1 salmonellosis of test example
1 material and method
1.1 drugs and reagent
Pharmaceutical composition (also known as intestines bacterium dissipates clearly) of the present invention: by radix scutellariae, Fructus Forsythiae, the coptis, Cortex Phellodendri, radix paeoniae rubra and Radix Glycyrrhizae prescription
At
Radix scutellariae 213g Fructus Forsythiae 213g coptis 85g
Cortex Phellodendri 340g radix paeoniae rubra 213g Radix Glycyrrhizae 85g
12.2 preparation methods
Above 6 taste crushes, and is sieved, and mixes, it is dry to get.
According to above-mentioned medicinal material formula and preparation method, animal pharmaceutical estate Co., Ltd, Tongwei Co., Ltd. produces and provides
Three different batches inspection qualified products: lot number 20111031；20111032；20111033.The product is yellow powder.
It is provisional to be used by design dosage with dispensing is raised.
Ciprofloxacin；The sensible animal health Science and Technology Ltd. in Sichuan, specification: 50g:1g, lot number: 20120101.With feeding
Dispensing.
Salmonella pullon (Salmonella pullorum), strain CVCC519, C79-3, S.pu.2；Serum
Type are as follows: 9,121,123 :-:-, it is purchased from China Veterinery Drug Inspection Office；
Buffered peptone water (BP): it is voluntarily prepared by 4.12 regulations in GB4789.28；
Rappaport vassiliadis mdeium (MM) culture medium, Beijing overpass Technology Co., Ltd. lot number 120213；
Mai Kangkai culture medium, Beijing overpass Technology Co., Ltd. lot number 120213；
SS culture medium, Beijing overpass Technology Co., Ltd. lot number 120213；
XLD culture medium, Beijing overpass Technology Co., Ltd. lot number 120213；
Lysine decarboxylase test broth, Beijing overpass Technology Co., Ltd. lot number 120213；
Triple sugariron culture medium, Beijing overpass Technology Co., Ltd. lot number 120213；
A-F polyvalent serum, Lanzhou Institute of Biological Products
1.2 test apparatus
Electronic balance, Chengdu Puruixun Electronics Co., Ltd；
755B ultraviolet-uisible spectrophotometer, Shanghai essence tech equipment Co., Ltd；
Superclean bench, SuZhou Antai Air Tech Co., Ltd.；
VITEK-2 full automatic microorganism analysis system, France bioMerieux；
Genex liquid-transfering gun, Shanghai Wo Yuan Science and Technology Ltd..
Other routine experiment instruments.
1.3 experimental animal
Luo Man layer of 1 age in days after MD vaccine immunity 500, it is limited purchased from Chongqing City great Zu Qu Mingji poultry farming
Chicken house is planted by company.Freely drink the tap water let cool through scalding, and with the full price chicken feed for being free of any antibacterials
Raising selects the chick of 450 clinical examination health as subjects to 3 ages in days.By there is duplicate random district's groups
Animal is divided into 10 groups and tested by design, and weight and grouping situation are shown in Table 1.
1.4 feeds are free of the complete feed of any antibacterials.Purchased from the honest Co., Ltd in Zhengda Group Chongqing.
The grouping of 1 test chicken of table and disposition *
| Number | Group | Number of animals | Weight | Processing |
| 1 | Healthy control group | 45 | 34.9±8.3 | Do not infect not medication, isolated rearing. |
| 2 | Infect control group | 45 | 37.1±6.7 | Infect not medication, isolated rearing. |
| 3 | C low dosage prevention group | 45 | 38.7±7.0 | 10mg·kg-1Weight, with raising, twice daily. |
| 4 | C middle dosage prevention group | 45 | 37.5±6.2 | 20mg·kg-1Weight, with raising, twice daily. |
| 5 | C high dose prevention group | 45 | 37.3±6.25 | 40mg·kg-1Weight, with raising, twice daily. |
| 6 | C low dose therapy group | 45 | 37.2±8.6 | 10mg·kg-1Weight, with raising, twice daily. |
| 7 | C middle dosage treatment group | 45 | 37.8±7.2 | 20mg·kg-1Weight, with raising, twice daily. |
| 8 | C high-dose therapy group | 45 | 37.3±6.45 | 40mg·kg-1Weight, with raising, twice daily. |
| 9 | CX positive drug prevention group | 45 | 37.4±6.6 | 20mg·kg-1Weight, with feeding, prevention administration. |
| 10 | CX positive drug treatment group | 45 | 37.8±6.2 | 40mg·kg-1Weight, with feeding, prevention administration. |
* 1, prevention group is 12h dispensing in advance, treats and is administered simultaneously for infection；
2, C represents intestines bacterium group scattered clearly；CX represents Ciprofloxacin group.
1.5 contamination bacterium solution preparations
Salmonella pullon (C79-13) be China Veterinary Drugs Supervisory Inst. reference culture.Egg is first inoculated in using preceding
36 ± 1 DEG C of culture 18h of white peptone buffer, then for 24 hours with 37 DEG C of scribing line cultures of ordinary flat, picking colonies typical is inoculated in common meat
37 DEG C of culture 18h, turbidimetric assay bacterial growth turbidity determine bacteria containing amount in soup.It is 6.75 × 10 by bacteria containing amount9The meat soup of a/L
Culture 0.25ml oral vaccination is non-to exempt from chicken rejuvenation, makes after the purifying agaric culture of the sterile separation rejuvenation of infection morbidity chicken liver
At contamination bacterium solution, and measuring quantitative bacterial concentration with Maxwell colorimetric method is 6.75 × 109A/L sets 4 DEG C of refrigerators and saves backup.
1.6 trial tests and the determination for attacking toxic dose
Before formal test, the 3 age in days healthy chicks for raising with field and raising under the same conditions are chosen, are connect by document is oral
Kind pathogenic strain, determines the minimal lethal dose MLD(10 of pathogenic strain9CFU/ is only).
Salmonella virulence prerun, takes a small amount of bacterium solution, makees 10 times of bacterium solutions for being diluted to various concentration with physiological saline, respectively
It is the 10 of stoste and stoste-1、10-2、10-3Concentration takes the close chicken of weight 50, is divided into 5 groups, every group 10, take orally respectively with
On not same amount or the bacterium solution of various concentration, observe chicken morbidity and death condition in 5d and record；The minimum lethal agent of 5 days animals
(MLD) is measured as this test and attacks toxic dose.
1.7 inoculum concentrations and bacterial population
Every chicken oral vaccination 1 × MLD salmonella bacterium solution.
1.7 dosages, the course for the treatment of and method
Each prevention group 12h before inoculation carries out preventive administration；When there is first morbidity chicken after inoculation in treatment group
Start to offer medicine；Infection control group fed does not add the basal diet of any drug；Healthy control group isolated rearing, does not appoint
Where reason.Freely drink cooling sterilizing ordinary water after boiling；The equal successive administration of each group 5 days, observation period are 8 days after inoculation.It gives
Pharmaceutical quantities, method are shown in Table 1.
1.7 index of assessment of curative effect
1.7.1 clinical observation
After animal inoculation pvaccination, in 1~8 day, clinical symptoms are observed day by day, and the state of mind, breath state, excrement, hind leg are closed
Section, amount of drinking water, feed intake etc. are observed, and carry out pathology dissect, bacterium separation identification to the chicken that dies of illness, and acquire chicken reality of dying of illness
Matter organ carries out the items contents such as pathological tissue observation and is tested, and observes and records test result.
1.7.2 the death rate
All to be prevented within experimental period or treatment is invalid, there is salmonellosis classical symptom and death in clinic, through cuing open
Cubing typical case's salmonellosis lesion characteristics, bacteriology separation, are accredited as positive, and it is dead to be determined as infection.According to death toll
Calculate each group death rate.
1.7.3 efficient
After the test, the percentage of test group is accounted in each group surviving animals as effective percentage.
1.7.4 cure rate
After medication, animal is without exception or restores normal, and no clinical symptoms person is to cure.It is controlled according to number calculating each group is cured
More rate.
1.7.5 feed intake
Each group feed intake is calculated with the difference of filling amount and surplus doses, and each test group is counted, it is average to obtain each group chicken
Feeding grain.Calculation formula is as follows: each group average daily gain (g)=(filling amount-remains doses)/number of animals
1.7.6 body weight increase rate
With the calculating of the ratio between the average weight gain of infection experiment group and the average weight gain of healthy control group, calculation formula is as follows:
1.7.7 the separation and identification of bacterium
Separation identification is carried out to bacterium by following check problem:
Sampling → Zengjing Granule → identification culture → biochemical investigation → serological test → result report.
1.7.7.1 acquisition and the Zengjing Granule of sample
The tested dead chicken of dissect, sterile separation simultaneously acquire liver blood, painstaking effort or ascites.Select broth medium and chlorine
Change magnesium malachite green bouillon (MM) culture based on Zengjing Granule 18 at 37 DEG C~for 24 hours, bacterium solution set 4 DEG C of refrigerators save it is to be checked.
1.7.7.2 identify the biochemical test of culture with bacterium
A small amount of Zengjing Granule bacterium solution is dipped with oese, streak inoculation is on XLD agar plate, Mai Kangkai culture medium.In
37 DEG C of culture 18h~for 24 hours, observation colony characteristics (it is recommended that morphological feature of description bacterium colony).Then, divide from XLD agar plate
Other picking meets 2 of salmonella cultural characteristic or more suspicious bacterium colonies, is seeded on triple sugar-iron-agar medium, first on inclined-plane
Scribing line is punctured then at bottom；Then it in the case where unsterilised after transfer needle inoculation, continues directly to be inoculated in lysine decarboxylase
Inoculated and cultured on test medium, 37 DEG C of culture 18h~for 24 hours, observe the growth characteristics of bacterium colony.It records and reports result.
Doubtful positive strain culture solution is carried out to biochemical identification, record in VITEK-2 full automatic microorganism analysis system
As a result.
1.8 data analysis and process
Selecting statistical software is that SPSS15.1 is for statistical analysis to data.The death rate, efficient chi-square criterion, weight gain are used
F is examined.
2. result
2.1 clinical effectiveness
Gradually appear different degrees of typical white scour of chicken clinical symptoms after Chickens Infected after 4h~8h, after 8h, chicken
Occur dead.Clinical disease one's own judgment: spirit is depressed or tired, and individual chicken pains pipe, and drinks loss of appetite, and loose random is exhaled
It inhales speedup, wheeze, both wings are sagging, and eye closing lethargic sleep, chilly gathers, and are reluctant to walk about, and draw white or green slurry shape loose stool, anus attached
Close or periphery faecal contamination, or stick white excrement blocking chick anus, chick group are often accompanied by sad and shrill shriek, in cage tool
Moist filthy, packing paper humidity has obvious loose stool.
Dead chicken pathology dissect major pathologic features are: liver hyperemia enlargement, being dispersed in property necrosis point, congestive heart,
There is intoxicated junket sample tubercle in hydropericardium, empsyxis or hyperemia, enteric hemorrhage, seroperitoneum, later period individual chick hearts, and hind leg closes
Save enlargement.Yolk malabsorption includes cheesy object, and intestinal mucosa falls off, and has a large amount of mucus shape whites to stagnate object in cloaca,
There are a large amount of mucus in oral cavity.From separation of bacterial such as liver, abdominal cavity, hearts, it is possible to identify infected for Salmonella.
Healthy control group chicken is during test without relevant clinical syndrome.
2.2 preliminary result
Preliminary result see the table below:
Table 2 attacks 5 days animal dead situations after malicious Salmonella pullorum
Table 2 the result shows that: the MLD of malicious chick is attacked through gastrointestinal tract as 0.25ml × 6.75 × 10 with the bacterial strain9A/L.
The disease incidence of 2.3 each test groups, the death rate, effective percentage, cure rate, weight gain, feed-weight ratio statistical result table.
The curative effect situation * of each test group of table 3
Note: data shoulder marking-up mother is identical in table, indicates that there was no significant difference (p > 0.05)；Conversely, significant difference (p <
0.05/0.01)
As shown in Table 3, intestines bacterium dissipates clearly the prevention for the white scour of chicken, middle dosage and high dose and the positive group of infection and low
Significant difference (p < 0.05/0.01) is deposited between dosage group；Its prevention morbidity effect is suitable compared with positive drug control group, morbidity
Rate is without significant difference (p > 0.05).The death rate also shows similar result.I.e. high middle dose group, the chick of positive drug group are dead
Rate is died, it is lower compared with low dose group and infection control group, have significant difference (p < 0.05/0.01)；Prevention administration obtains healing
Rate table 3 is shown: prevent the chick of high dose group in dissipating clearly to intestines bacterium, cure rate relatively infection positive controls when off-test and
Low dose group is high, has significant difference (p < 0.05), but lower compared with positive drug control.
Table 3 is also shown: intestines bacterium dissipates clearly for treating the white scour of chicken, the death of high middle dose group, positive drug control group
Rate is lower, has significant difference (p < 0.05) compared with low dose group, infection positive controls.Cure rate on the 5th is also higher, with sense
Dye control group and low dose group are compared, and are had significant difference (p < 0.05).But it is lower than positive drug group (p < 0.05).
To sum up experimental result prompts, the prevention and treatment that can be used for the white scour of chicken scattered clearly of intestines bacterium, under high, middle dosage
Activity is suitable with positive Antibiotics drug, shows in the prevention and treatment for the white scour of chicken, intestines bacterium clears can replace entirely clearly
For antibiotic usage.
2.4 death separation of bacterial identification results
By dead diseased chicken dissect, sterile coring blood, liver blood or abdominal cavity ascites culture and identification culture, result are as follows:
4 dead animal bacterium of table is separately cultured and identification result
As the result is shown: it is significantly high that salmonella death chicken separates positive rate infected group, low dosage intestines bacterium medication group scattered clearly
In middle dosage, high dose medication group and positive drug control group.It is further noted that: either intestines bacterium dissipates medication group also clearly
It is to there is different animals to divide in the painstaking effort of dead chicken, liver, lung or abdominal cavity in the dead chicken of positive drug control group
Bacterium is separated out, through Preliminary Identification in addition to the salmonella for thering is infection to attack poison, there are also Some Animals ehec infection, lethal original
Because that may have certain relationship with the secondary infection of Escherichia coli except having outside the Pass with salmonella infection.
2.5 death histopathologic slides analyze result (see Fig. 1~6)
To all groups die of illness chick acquire the heart, liver, spleen, lung, caecum carry out pathology section examination.Control group chick exists
It cuts open within 6th day and above-mentioned tissue is taken to carry out sections observation after killing.
As the result is shown: morbidity chick shows the pathologic processes such as inflammation, bleeding, extravasated blood, denaturation, the necrosis of each tissue.Its
In it is the most serious to infect control group chick pathological change of dying of illness.And intestines bacterium dissipates clearly middle dosage, the high dose control group of control group
Die of illness chick, overall pathology section examination, and basic pathology change procedure and the infected group chick that dies of illness are similar.But it can see
Out, relatively slight in the degree of pathological change, and individual tissues have rehabilitation after apparent inflammatory process to show.Certainly, therein
The lesion tissue of positive drug control group prevention group is the slightest.Thus as the result is shown: although dissipating prevention clearly using intestines bacterium and controlling
Treat the death that the white scour of chicken is still likely to occur chick.But there is basic pathology process caused by pathogenic bacteria lighter.In fact from when death
Between and the death rate also obtained corresponding evidence.Intestines bacterium, which dissipates clearly, has certain suppression to pathologic process caused by mitigation salmonellosis
Production is used.And preferable preventive and therapeutic effect thus can be played to the prevention and treatment white scour of chicken.
3. discussion and conclusion
3.1 Salmonella pullorum diseases (pullorum disease), abbreviation white diarrhea is by Salmonella pullon
The infectious disease that caused various age chickens often send out.This disease not only brings serious harm to poultry husbandry, results in significant economic losses,
And S. pullonum can be colonized in poultry intestinal tract, polluted egg or when processing poultry ketoboidies, polluted chicken, after
And enter human foods chain, become the potential source of mankind's salmonella infection.So pass of the prevention and treatment of white diarrhea by people
Note.
In recent years, some chicken disease experts think that white diarrhea should be listed in the first place of chicken disease.Studies have found that 1~4 day in recent years
Age day old chick disease incidence increased significantly, and the chicken morbidity and mortality within 2 week old are all very high.It is brought sternly to poultry husbandry
The harm of weight.Although antibiotic, antibacterials, such as clinically common cephalosporins semisynthetic antibiotics, aminoglycoside
Antibiotic, tetracycline antibiotics, fluoroquinolones antimicrobial DP finish, disulfonamide etc. have certain effect to the disease is prevented and treated
Fruit can effectively reduce the morbidity and mortality of white diarrhea.But as treatment be not thorough and long-term Irrational Use of Drugs caused by
The increase of antibody-resistant bacterium increases the difficulty for preventing and treating the disease.In addition drug resistance salmonella and salmonella and Escherichia coli it
Between drug resistance transmitting and diffusion, the infection of drug resistance salmonella has become the difficult point for preventing and treating the disease at present.And drug resistance
The wide-scale distribution of salmonella has become potential public health harm problem.Therefore carry out the prevention and treatment of white scour of chicken salmonellosis
Drug research has great importance.Wherein, Chinese medicine, especially Chinese medicine compound prescription are because its adverse reaction is small, be not easy to remain, do not pollute
Environment is not likely to produce unique advantage possessed by drug resistance, is expected to obtain increasingly important role in terms of preventing and treating the disease.
3.2 this test press 0.25ml × 6.75 × 10 to 3 ages in days test chick9A/L(1 × MLD) take orally C79-13It is husky
Men Shi bacillus liquid suspension replicates artificial DISEASE IN FLOCKS pathological model and obtains success.Infection morbidity chick is after oral vaccination
Phase secondary disease after 4h~8h.It is fallen ill, and chick Major Clinical symptoms include spirit are depressed, are short of breath, have difficulty in breathing, piping, arranging white
Serosity excrement, anus are blocked by serosity excrement, are dehydrated, is thin, and are occurred in succession after 8h~12h in turn dead.After death
Dissect is visible: serious dehydration, enteron aisle hyperemia, bleeding, and gassy in enteron aisle, mucous membrane changes in acute inflammation, and liver extravasated blood goes out
Blood, the canescence spotty necrosis point on the visible liver surface of individual chick, empsyxis, yolk bag absorb not congruent disease.Pathological section
It observes the major lesions such as the visible heart, lung, liver, spleen, caecum organ and the disease substantially such as different degrees of bleeding, denaturation, necrosis occurs
Reason process.It acquires morbidity chicken anus swab (excrement) separation of bacterial and dies of illness chicken gizzard, the heart, abdominal cavity separation of bacterial through bacteriology checking
Prove that morbidity chick and dead chick are mainly caused by attacking toadstool in relation to (see Table 4 for details；Fig. 1~6).This result explanation uses this examination
Artificial challenge's pathological model of proved recipe method duplication can guarantee being normally carried out for this test completely.
3.3 test results of the present invention show: intestines bacterium dissipates clearly middle and high dose application in the white scour of chicken case of artificial challenge,
Premix addition, is used in conjunction 5d, can effectively reduce Chickens Infected disease incidence, and infection chick morbidity case fatality rate is effectively reduced.With infection
Control group and low dose group, which are compared, has significant difference.And the protective effect, with positive control medicine Ciprofloxacin pre-mixing agent
Protecting effect is quite (see Table 2 for details).In addition test result is also shown: even if the dead chick after medication, also shows using height
After middle dosage intestines bacterium dissipates clearly, the morbidity death time can be slowed down, the pathology for mitigating metainfective intestines, liver, lung, spleen and caecum etc. becomes
Change (being detailed in Fig. 1~6).This result shows that: intestines bacterium clearly dissipate with prevention and treatment salmonella infection chick cause DISEASE IN FLOCKS compared with
Remarkable result.Test result affirmative intestines bacterium dissipates clearly the clinical effect for preventing and treating the white scour of chicken.
Claims (4)
1. the purposes of pharmaceutical composition as described below in the drug of preparation prevention or treatment Salmonella pullorum disease；It is described
Pharmaceutical composition is the preparation being prepared by the bulk pharmaceutical chemicals of following weight proportion:
185 parts of radix scutellariae, 185 parts of Fructus Forsythiae, 185 parts of radix paeoniae rubra, 74 parts of the coptis, 297 parts of Cortex Phellodendri, 74 parts of Radix Glycyrrhizae.
2. purposes according to claim 1, it is characterised in that: the drug is prevention or treatment Salmonella pullorum
The drug of disease.
3. purposes according to claim 1 or 2, it is characterised in that: the drug is with the weight proportion bulk pharmaceutical chemicals
The water or/and extractive with organic solvent of medicinal powder or bulk pharmaceutical chemicals be active constituent, in addition pharmaceutically common auxiliary material or it is complementary at
Divide the preparation being prepared.
4. purposes according to claim 3, it is characterised in that: the organic solvent is ethyl alcohol or hydrous ethanol.
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