CN107802651A - Inactivate application of the lactic acid bacteria in viral disease medicine is prevented and treated - Google Patents
Inactivate application of the lactic acid bacteria in viral disease medicine is prevented and treated Download PDFInfo
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- CN107802651A CN107802651A CN201610809345.0A CN201610809345A CN107802651A CN 107802651 A CN107802651 A CN 107802651A CN 201610809345 A CN201610809345 A CN 201610809345A CN 107802651 A CN107802651 A CN 107802651A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/745—Bifidobacteria
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
Abstract
The present invention relates to a kind of purposes for inactivating lactic acid bacteria in preventing and treating viral disease medicine is prepared, belong to biomedicine field.The main component of this medicine is inactivation lactic acid bacteria, can be by the way that lactic acid bacteria living is prepared by conventional method inactivation.Inactivation lactic acid bacteria intravenously administrable can be used for prevention, treatment or the auxiliary treatment of the various viral diseases of human or animal, have broad application prospects.
Description
Technical field
The invention belongs to biomedicine field, more particularly to new application of the inactivation lactic acid bacteria in viral disease is prevented and treated.
Background technology
Viral disease seriously threatens human and animal's health.In people doctor clinically, the viral disease kind of generation
Class is more, as AIDS, virus hepatitis, influenza, Japanese Type-B encephalitis, SARS, ebola disease viral disease,
Dengue fever, viral hemorrhagic fever, rotavirus diarrhea, herpes zoster, hand-foot-and-mouth disease, mumps etc..Once by A type stream
The deadly infectious disease of the initiations such as Influenza Virus, SARS virus and Ebola virus causes the massive loss of life.In addition some chronic biographies
Such as AIDS, hepatitis B of catching an illness remain difficult to cure at present.On veterinary clinic, equine infectious anemia, the Niu Kou of generation
The various virosis such as fever aphthous, sheep PPR, swine fever, bird flu cause significant damage to livestock and poultry breeding industry；Pet occurs
Canine distemper, parvovirus often cause dog dead.Reply viral disease is frequently with vaccine inoculation and medical treatment at present
Method.Because viral constantly variation, vaccine prevention and control also tend to fail, in addition, some new infectious diseases break out suddenly, vaccine there is no
It is controllable.
The antiviral drugs used at present have Ribavirin, amantadine, Oseltamivir, abitilguanide, Valaciclovir, Ah
Sugared adenosine, Lamivudine etc., virus can be also set to produce drug resistance using antiviral agent in large quantities for a long time, such as some influenza viruses pair
Amantadine generates drug resistance.Anti virus herb clinical practice is also relatively broad, as Shuanghuanglian oral liquid, Qingkailing granule,
Yinqiao San, Pudilan piece etc., though Chinese medicine is antiviral curative for effect, it also is difficult to reach ideal effect sometimes.It is other kinds of anti-
Viral medicine also has some antibody classes, such as antiserum, gamma immune globulin, Yolk antibody.In addition, some immunopotentiators
It is usually used in the auxiliary treatment of virosis, such as astragalus polyose, transfer factor, interferon.Although currently used for preventing and treating virosis medicine
The species of thing is many, but because some viral pathogenesis power are strong and easily make a variation and produce drug resistance, difficulty of prevention and cure is larger, therefore
It is extremely important to find new antiviral drugs.
Present invention discover that the lactic acid bacteria of inactivation is carried out into intravenously administrable, highly effective, future tool is prevented and treated viral disease
Have broad application prospects.The relevant report that will inactivate lactic acid bacteria intravenously administrable for preventing and treating viral disease is there is no at present.
The content of the invention
The invention provides a kind of brand-new inactivation lactic acid bacteria intravenous injection that can be used for viral disease preventing and treating, this
The main component of kind medicine is the lactic acid bacteria of inactivation, and the medical intravenous, which is administered, can effectively prevent and treat viral disease.
Inactivate lactic acid bacteria and preparing the purposes in preventing and treating viral disease medicine, it is blue that leather is carried out to described inactivation lactic acid bacteria
Albert'stain Albert, in oily Microscopic observation, inactivation lactic acid bacteria keeps complete thalli morphology, and the administering mode of medicine is drug administration by injection.It is described
The complete thalli morphology of holding refer to inactivate before viable bacteria thalline profile and form it is basically identical.Described basically identical essence
On refer to somatic cells wall in lactic acid bacteria inactivation process it is possible that slight change, such as the loss of part surface composition, but
It is this to change very little or seldom generation.
It is 10 that the complete thalline quantity of inactivation lactic acid bacteria is included in described per unit dose medicine5—1012It is individual.
Described drug administration by injection is administered for intravenous injection.Inactivated using HTHP, the inactivation of ultraviolet inactivation, chemical reagent
Or any of radiological inactivation ablation method obtains the inactivation lactic acid bacteria.
The kinds of lactobacillus of inactivation lactic acid bacteria intravenous injection is prepared for the present invention to be included：(1) lactobacillus：De Shi breasts
It is bacillus (L.delbrueckii), lactobacillus bulgaricus (L.bulgaricus), Lactobacillus helveticus (L.helviticus), thermophilic
Lactobacillus lactis (L.acidophlus), lactobacillus gasseri (L.gasseri), Lactobacillus salivarius (L.salivarius), plant breast
Bacillus (L.plantarum), lactobacillus reuteri (L.reuteri), Lactobacillus brevis (L.brevis), Lactobacillus casei
(L.casei), lactobacillus fermenti (L.fementi) etc.；(2) Pediococcus：Such as Pediococcus acidilactici (P.acidi1actic), penta
Sugar-tablet coccus (P.pentasiaceus), Pediococcus parvulus (P.parvulus) etc.；(3) Leuconostoc：The bright string coccus of goldbeater's skin
And its subsp. cremoris (L.cremoris) and dextranicum (Leuc.dextranicun), lactic acid (L.mesenteroides)
Bright string coccus (L.lactis), the bright string coccus (L.oenos) of wine etc.；(4) enterococcus spp：VREF (E.faecium), excrement intestines
Coccus (E.faecalis) etc.；(5) lactococcus：Lactococcus lactis subsp. lactis (L.lactis subsp.lactis), lactic acid
Lactis subsp. cremoris (L.lactis subsp.cremoris), Lactococcus lactis leafhopper subspecies (L.lactis
Subsp.hordniae) etc.；(6) streptococcus：Streptococcus lactis (S.lactis), diacetyl streptococcus lactis
(S.diacetilactis), streptococcus cremoris (S.creamoris), streptococcus thermophilus (S.thermophilus) etc.；(7)
Bifidobacterium：Bifidobacterium bifidum (B.bifidum), bifidobacterium longum (B.longum), bifidobacterium breve (B.breve),
Bifidobacterium infantis (B.infantis), bifidobacterium adolescentis (B.adolescentis), animal bifidobacteria
(B.animalis) etc.；(8) lactic acid bacteria of other kinds.
Preferably, lactic acid bacteria is selected from Lactococcus lactis subsp. lactis (latin name：Lactococcus lactis
Subsp.Lactis, deposit number：CICC 6246), Lactobacillus plantarum plant subspecies (latin name：Lactobacillus
Plantarum subsp.Plantarum, deposit number：CICC 6240), bifidobacterium longum (latin name：
Bifidobacterium longum, deposit number：CICC 6196), Lactobacillus brevis (latin name：Lactobacillus
Brevis, deposit number：CICC 6239), VREF (latin name：Enterococcus faecium, deposit number：
CICC 6049)。
Formulation for the preparation inactivation lactic acid bacteria intravenously administrable of the present invention includes：Powder-injection, mixed suspension injection etc. are various
Formulation.Administering mode for the inactivation lactic acid bacteria intravenous injection of the present invention includes：Intravenous injection and drip-feed etc..
The present invention has inactivated VREF using conventional method, finds the VREF of inactivation and still can carry out gram
The thalline profile and form that dyeing, the VREF of oily Microscopic observation inactivation and the VREF to live are consistent.Then to going out
VREF normal saline suspension living is centrifuged, and is abandoned supernatant and is stayed precipitation, extracts DNA, can still be amplified using round pcr
16S rDNA genetic fragments, kinds of lactobacillus discriminating can also be carried out by sequencing.Further study show that dung intestines ball will be inactivated
Mouse tail vein is administered bacterium, can be effectively reduced the death toll of influenza virus PR8 strain infecting mouses；It is quiet to inactivate VREF
The death toll that can also significantly reduce ewcastle disease infected chicken is administered in arteries and veins；Inactivating Lactobacillus plantarum plant subspecies intravenously administrables can be with
Effectively prevent and treat the generation of pig blue-ear disease.Inactivation lactic acid bacteria intravenously administrable described above can be used for the preventing and treating of viral disease.
The inactivation lactic acid bacteria intravenous injection of the present invention can be used for the preventing and treating of various viral diseases, bag through intravenously administrable
Include：(1) the various viral diseases of people, such as AIDS, virus hepatitis, influenza, Japanese Type-B encephalitis, atypia
Pneumonia, ebola disease viral disease, dengue fever, viral hemorrhagic fever, rotavirus diarrhea, herpes zoster, hand-foot-and-mouth disease, the popular cheek
Adenositis, measles, rubella, adenopathy viral disease etc.；(2) the various virosis of domestic animal, such as swine fever, porcine reproductive and respiratory syndrome, pig circle
Circovirus virus disease, porcine parvovirus, pseudorabies, transmissible gastroenteritis of swine, pig epidemic diarrhea, pig encephalitis B, pig blister
Venereal disease, swine flu, swine pox, aftosa, Bovine Respiratory Syncytial virosis, infectious bovine rhinotrachetis, bovine viral diarrhoea, ox
Parainfluenza, bovine rota disease, capripox virus disease, PPR, equine influenza, equine infectious anemia etc.；(3) poultry is each
Kind virosis, such as bird flu, newcastle disease, Bursal Disease, infectious bronchitis of chicken, chicken infectivity throat tracheae
Inflammation, chicken pox, chicken Marek's disease, duck plague, duck virus hepatitis, Duck Paramyxovirus disease disease, Duckling flavivirus disease, Duck parvovirus disease,
Gosling plague, goose paramyxovirus etc.；(4) the various virosis of pet, as canine distemper, canine parvovirus disease, canine infectious hepatitis,
Rabies, cat distemper heat etc..
The mechanism of intravenous injection inactivation lactic acid bacteria preventing and treating viral disease is not fully understood at present, thus it is speculated that possible mechanism
It is：Lactic acid bacteria intravenously administrable is inactivated, may be interacted with virus, blocking virus infected tissue organ；It may also inactivate
After lactic acid bacteria intravenously administrable antiviral substance is generated through organism metabolism；Or body can be activated after inactivation lactic acid bacteria intravenously administrable
Immune system, antivirus action etc. is played indirectly.
Embodiment
Embodiment 1
VREF (is purchased from Chinese industrial Microbiological Culture Collection administrative center, latin name：Enterococcus
Faecium, deposit number：CICC 6049) MRS culture mediums are inoculated in, in 37 DEG C of incubator cultures 24 hours, then 3000 leave
The heart 5 minutes, remove culture supernatants and retain precipitation, add sterile saline cleaning precipitation, centrifuge 5 minutes, repeated washing 3 times
Afterwards, sterile saline is added, is mixed with precipitation.A certain amount of VREF normal saline suspension is taken, in spectrophotometer
Its OD value is measured at 690nm, when the OD values of the ultimate density diluted with sterile saline are 0.38, by the diluted concentration
For VREF normal saline suspension as 1 times of (1 ×) concentration, carrying out bacteria count by THOMA bateria chambers should
Contain about 10 in every mL suspensions under concentration8Individual VREF thalline.The VREF physiological saline of 1 a small amount of × concentration is taken to mix
Suspension, Gram's staining is carried out, in the form of oily Microscopic observation viable bacteria.Hereafter the VREF of the 1 × concentration prepared is given birth to
Salt aqueous suspension is managed in 121 DEG C, pressure 0.12MPa, 15min is inactivated, obtains inactivating VREF suspension, take a small amount of suspension
Gram's staining is carried out, in the form of oily Microscopic observation inactivation thalline, it is found that inactivation lactic acid bacteria keeps complete thalli morphology, with it
Viable bacteria thalline profile is consistent with form before inactivation, and thalline quantity does not have significant change before and after count of bacteria finds inactivation.
Embodiment 2
VREF (is purchased from Chinese industrial Microbiological Culture Collection administrative center, latin name：Enterococcus
Faecium, deposit number：CICC 6049) MRS culture mediums are inoculated in, in 37 DEG C of incubator cultures 24 hours, then 3000 leave
The heart 5 minutes, remove culture supernatants and retain precipitation, add 0.9% sterile physiological salt cleaning precipitation, centrifuge 5 minutes, repeated washing
After 3 times, appropriate 0.9% sterile saline is added, is mixed with precipitation.A certain amount of lactic acid bacteria suspension is taken, in spectrophotometric
Count and its OD value is measured at 690nm, when the OD values of the ultimate density diluted with sterile saline are 0.38, will so dilute dense
The lactic acid bacteria suspension of degree is as 1 times of (1 ×) concentration.On this basis, to carrying out different multiples containing lactic acid bacteria physiological saline
Normal saline dilution, can with obtain 5 ×, 1 × and 0.2 × concentration lactic acid bacteria suspension.Hereafter 5 will prepared respectively
×, 1 × and 0.2 × concentration VREF suspension in 121 DEG C, pressure 0.12MPa, inactivate 15min, obtain 5 ×, 1 × and
The inactivation VREF suspension medicine of 0.2 × concentration.Detect the shadow of suspension infected by influenza PR8 strain infecting mouse death toll
Ring.Experiment is divided into Normal group, PR8 strains model group (i.e. influenza virus PR8 strains from 18-22g cleaning grade Kun Ming mices
Infecting mouse model group) and high, medium and low three dosage inactivation VREF administration group.Every group of 30 mouse, male and female half and half.
The inactivation lactic acid bacteria group of high, medium and low three dosage respectively tail vein injection 5 ×, 1 × and 0.2 × concentration inactivation VREF
Intravenous injection；Normal group and PR8 strain model group tail vein injection sterile salines, each group administered volume are
0.1mL/10g.Each group mouse is spaced 24 hours after being administered once, and in addition to Normal group, other each group mouse are slight in ether
In the chick embryo allantoic liquid of intranasal vaccination PR8 containing influenza virus strains under anesthesia, every 0.05mL, infect influenza virus PR8 strains
Mouse.Hereafter each group dead mouse number in 10 days is observed and recorded.The inspection of card side is carried out to experimental data using the softwares of SPSS 11.5
Test, the results are shown in Table 1.As shown in Table 1, high, the inactivation VREF administration group of middle dosage is compared with PR8 strain model groups, can be with
Pole significantly reduces dead mouse number, and low dosage administration group can significantly reduce dead mouse compared with PR8 strain model groups
Number.Inactivation VREF injection described above can be used for preventing and treating viral disease.
Table 1 inactivates the influence result of VREF intravenously administrable infected by influenza PR8 strain infecting mouses
Note：* represents often to organize with normal control poor with the notable P ＜ 0.01 of the poor heteropole of Normal group, * expressions
Different significantly P ＜ 0.05；△ △ represent to represent and PR8 strain model groups with the notable P ＜ 0.01 of the poor heteropole of PR8 strain model groups, △
The notable P ＜ 0.05 of comparing difference.
Embodiment 3
The inactivation VREF suspension of 10 × concentration is prepared according to the method for embodiment 2 and inactivation VREF used,
Preventive and therapeutic effect of the research inactivation VREF administration to newcastle disease.Ewcastle disease control is randomly divided into from 10 age in days white meat-type chickens
Group, inactivation VREF high dose group and inactivation VREF low dose group, every group 30.High dose and low dosage inactivation dung intestines
The dosage of coccus group be respectively intravenous injection 10 under wing × inactivation VREF normal saline suspension 0.05mL/ only and
0.1mL/ is only.Physiological saline is injected intravenously under ewcastle disease control group wing.Poison is attacked after 24 hours to intravenous injection administration under chicken wings, often
Allantoic fluid 0.2mL of the group chicken muscle injection containing NDV.Continuous Observation 5 days, record death toll.Using SPSS 11.5
Software carries out Chi-square Test to data, the results are shown in Table 2.As shown in Table 2, the inactivation VREF intravenously administrable of high dose can show
Writing reduces the death toll of chicken, illustrates that inactivating lactic acid bacteria can be used for preparing poultry viral disease medicine.
Table 2 inactivates preventing and treating result of the VREF intravenously administrable to newcastle disease
Note：* represents to represent compared with ewcastle disease control group with the notable P ＜ 0.01 of the poor heteropole of ewcastle disease control group, *
Significant difference P ＜ 0.05.
Embodiment 4
Lactobacillus plantarum plant subspecies (are purchased from Chinese industrial Microbiological Culture Collection administrative center, latin name：
Lactobacillus plantarum subsp.Plantarum, deposit number：CICC 6240) according to the method system of embodiment 2
The inactivation Lactobacillus plantarum plant subspecies suspension of standby 10 × concentration, detection inactivation Lactobacillus plantarum plant subspecies administration are blue to pig
The preventive and therapeutic effect of otopathy.16 health pigs of purchase are randomly divided into normal group, blue otopathy model group, prevention administration group and therapeutic administratp
Group, every group 4.Reproductive and respiratory syndrome virus liquid 2mL is injected using every pig posterior auricular muscle meat, prepares pig blue-ear disease model.Prevention administration group
Pig ear vein inject the inactivation Lactobacillus plantarum plant subspecies suspension 1mL of 10 × concentration, carry out within second day attacking poison prepare it is blue
Otopathy model；The inactivation that the pig of therapeutic administratp group ear vein on the day of after attacking poison and preparing blue otopathy model injects 10 × concentration is planted
Thing lactobacillus plant subspecies suspension 1mL, blue otopathy model group pig attack poison prepares after blue otopathy model on the day of ear vein note
Penetrate 1mL sterile salines.Normal group pig ear vein injects 1mL sterile salines.Hereafter the feed intake of 10 days pigs is observed
And cosmetic variation, it the results are shown in Table 3.4 pigs of blue otopathy model group fall ill, and show as fried hair and become thin, feed intake is decreased obviously；
4 pigs of therapeutic administratp group fall ill, and also show as fried hair and become thin, feed intake declines；And 4 pigs of prevention administration group are without morbidity
Symptom, i.e., become thin phenomenon without fried hair, appetite is slow compared with normal group, but feed intake does not decline.It is described above, inactivate Lactobacillus plantarum
Injection made of plant subspecies can effectively prevent and treat the generation of pig blue-ear disease.
Table 3 inactivates the influence that Lactobacillus plantarum plant subspecies intravenously administrable is fallen ill to blue otopathy
Claims (10)
1. inactivating lactic acid bacteria is preparing the purposes in preventing and treating viral disease medicine, it is characterised in that to described inactivation lactic acid
Bacterium carries out Gram's staining, and in oily Microscopic observation, inactivation lactic acid bacteria keeps complete thalli morphology, the formulation of medicine for suspension or
Powder-injection, administering mode are drug administration by injection.
2. purposes according to claim 1, it is characterised in that described lactic acid bacteria is selected from lactobacillus, enterococcus spp, galactococcus
Category, Bifidobacterium, Leuconostoc, streptococcus.
3. purposes according to claim 1, it is characterised in that the lactic acid bacteria is selected from Lactococcus lactis subsp. lactis and (drawn
Fourth title：Lactococcus lactis subsp.Lactis, deposit number：CICC 6246), Lactobacillus plantarum plant subspecies
(latin name：Lactobacillus plantarum subsp.Plantarum, deposit number：CICC 6240), long bifid
Bacillus (latin name：Bifidobacterium longum, deposit number：CICC 6196), Lactobacillus brevis (latin name：
Lactobacillus brevis, deposit number：CICC 6239), VREF (latin name：Enterococcus
Faecium, deposit number：CICC 6049).
4. purposes as claimed in claim 1, it is characterised in that inactivation lactic acid bacteria mixes for one or more kinds of inactivation lactic acid bacterias
Compound.
5. purposes according to claim 1, it is characterised in that inactivated using HTHP, the inactivation of ultraviolet inactivation, chemical reagent
Or any of radiological inactivation ablation method obtains the inactivation lactic acid bacteria.
6. purposes according to claim 1, it is characterised in that the drug administration by injection is administered for intravenous injection.
7. purposes according to claim 6, it is characterised in that during drug administration by injection, inactivation breast is included in every ml dose drugs
The sour complete thalline quantity of bacterium is 105—1012It is individual.
8. purposes according to claim 7, it is characterised in that described medicine is prepared as follows to obtain：By breast
After sour bacterium carries out conventional liq medium culture 12-36 hours, 3000-5000 leaves the heart and retains precipitation, then will precipitate fully clear
After washing, required concentration suspensions are configured to, in 120-122 DEG C, pressure 0.1-0.2MPa, inactivation 15-30min obtains inactivating lactic acid
Bacterium injection.
9. according to the purposes described in claim any one of 1-8, it is characterised in that described viral disease include AIDS,
Virus hepatitis, influenza, Japanese Type-B encephalitis, SARS, ebola disease viral disease, dengue fever, it is viral go out
Blood-head, rotavirus diarrhea, herpes zoster, hand-foot-and-mouth disease, mumps, measles, rubella, adenopathy viral disease, swine fever, pig are numerous
Grow and respiration syndrome, Porcine circovirus desease, porcine parvovirus, pseudorabies, transmissible gastroenteritis of swine, pig epidemic
Rush down, pig encephalitis B, pig blister venereal disease, swine flu, swine pox, aftosa, Bovine Respiratory Syncytial virosis, ox infectiousness nose gas
It is Guan Yan, bovine viral diarrhoea, bovine parainfluenza, bovine rota disease, capripox virus disease, PPR, equine influenza, equine infectious
Anemia.
10. according to the purposes described in claim any one of 1-8, it is characterised in that the viral disease includes bird flu, chicken
Ewcastle disease, Bursal Disease, infectious bronchitis of chicken, infectious laryngotracheitis of chicken, chicken pox, chicken Marek's disease,
Duck plague, duck virus hepatitis, Duck Paramyxovirus disease disease, Duckling flavivirus disease, Duck parvovirus disease, gosling plague, goose paramyxovirus, dog
Pest heat, canine parvovirus disease, canine infectious hepatitis, rabies, cat distemper heat.
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| CN108743624A (en) * | 2018-06-19 | 2018-11-06 | 华中农业大学 | Applications of the lactobacillus plantarum ZN-3 in preparing the drug for treating or preventing Porcine epidemic diarrhea virus infection |
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| CN114470187A (en) * | 2022-01-30 | 2022-05-13 | 山东农业大学 | Pharmaceutical composition for intravenous injection, preparation containing same, preparation method and application thereof |
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