CN107802652A - 灭活乳酸菌在防治细菌性疾病药物中的应用 - Google Patents
灭活乳酸菌在防治细菌性疾病药物中的应用 Download PDFInfo
- Publication number
- CN107802652A CN107802652A CN201610809582.7A CN201610809582A CN107802652A CN 107802652 A CN107802652 A CN 107802652A CN 201610809582 A CN201610809582 A CN 201610809582A CN 107802652 A CN107802652 A CN 107802652A
- Authority
- CN
- China
- Prior art keywords
- lactic acid
- acid bacteria
- inactivated
- inactivation
- injection
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 title claims abstract description 88
- 241000894006 Bacteria Species 0.000 title claims abstract description 69
- 235000014655 lactic acid Nutrition 0.000 title claims abstract description 25
- 239000004310 lactic acid Substances 0.000 title claims abstract description 25
- 239000003814 drug Substances 0.000 title claims abstract description 19
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 22
- 230000000415 inactivating effect Effects 0.000 claims abstract 2
- 241000194031 Enterococcus faecium Species 0.000 claims description 41
- 239000000725 suspension Substances 0.000 claims description 26
- 230000002779 inactivation Effects 0.000 claims description 18
- 238000002347 injection Methods 0.000 claims description 14
- 239000007924 injection Substances 0.000 claims description 14
- 240000001929 Lactobacillus brevis Species 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 9
- 241001608472 Bifidobacterium longum Species 0.000 claims description 8
- 235000013957 Lactobacillus brevis Nutrition 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 8
- 241000194017 Streptococcus Species 0.000 claims description 7
- 229940009291 bifidobacterium longum Drugs 0.000 claims description 7
- 241000194041 Lactococcus lactis subsp. lactis Species 0.000 claims description 6
- 241000186660 Lactobacillus Species 0.000 claims description 5
- 240000006024 Lactobacillus plantarum Species 0.000 claims description 5
- 244000164595 Lactobacillus plantarum subsp plantarum Species 0.000 claims description 5
- 235000012523 Lactobacillus plantarum subsp plantarum Nutrition 0.000 claims description 5
- 235000014969 Streptococcus diacetilactis Nutrition 0.000 claims description 5
- 229940039696 lactobacillus Drugs 0.000 claims description 5
- 238000010253 intravenous injection Methods 0.000 claims description 4
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 3
- 241000186000 Bifidobacterium Species 0.000 claims description 3
- 235000013965 Lactobacillus plantarum Nutrition 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 238000001647 drug administration Methods 0.000 claims description 3
- 229940072205 lactobacillus plantarum Drugs 0.000 claims description 3
- 230000001717 pathogenic effect Effects 0.000 claims description 3
- 231100000255 pathogenic effect Toxicity 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 241000196324 Embryophyta Species 0.000 claims description 2
- 241000194033 Enterococcus Species 0.000 claims description 2
- 241000192125 Firmicutes Species 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 238000001556 precipitation Methods 0.000 claims 2
- FRXSZNDVFUDTIR-UHFFFAOYSA-N 6-methoxy-1,2,3,4-tetrahydroquinoline Chemical compound N1CCCC2=CC(OC)=CC=C21 FRXSZNDVFUDTIR-UHFFFAOYSA-N 0.000 claims 1
- 241000192132 Leuconostoc Species 0.000 claims 1
- 241001052560 Thallis Species 0.000 claims 1
- 238000002679 ablation Methods 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- 238000010186 staining Methods 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 abstract description 18
- 230000002265 prevention Effects 0.000 abstract description 7
- 241001465754 Metazoa Species 0.000 abstract description 5
- 238000007796 conventional method Methods 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 29
- 241000607142 Salmonella Species 0.000 description 24
- 241000283690 Bos taurus Species 0.000 description 15
- 208000015181 infectious disease Diseases 0.000 description 12
- 244000052616 bacterial pathogen Species 0.000 description 10
- 241001354013 Salmonella enterica subsp. enterica serovar Enteritidis Species 0.000 description 8
- 238000004321 preservation Methods 0.000 description 8
- 210000003462 vein Anatomy 0.000 description 8
- 241000282465 Canis Species 0.000 description 7
- 241000194035 Lactococcus lactis Species 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 230000034994 death Effects 0.000 description 7
- 231100000517 death Toxicity 0.000 description 7
- 241001494479 Pecora Species 0.000 description 6
- 230000001580 bacterial effect Effects 0.000 description 6
- 235000013365 dairy product Nutrition 0.000 description 6
- 230000002458 infectious effect Effects 0.000 description 6
- 208000004396 mastitis Diseases 0.000 description 6
- 241000287828 Gallus gallus Species 0.000 description 5
- 241000204031 Mycoplasma Species 0.000 description 5
- 235000014897 Streptococcus lactis Nutrition 0.000 description 5
- 230000001665 lethal effect Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 241000283073 Equus caballus Species 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 244000005700 microbiome Species 0.000 description 4
- 239000002504 physiological saline solution Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 230000003449 preventive effect Effects 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 206010006500 Brucellosis Diseases 0.000 description 3
- 241000193403 Clostridium Species 0.000 description 3
- 208000004145 Endometritis Diseases 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 238000003794 Gram staining Methods 0.000 description 3
- 238000012449 Kunming mouse Methods 0.000 description 3
- 206010034107 Pasteurella infections Diseases 0.000 description 3
- 241000192001 Pediococcus Species 0.000 description 3
- 206010035664 Pneumonia Diseases 0.000 description 3
- 241000282898 Sus scrofa Species 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 229940124350 antibacterial drug Drugs 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000000546 chi-square test Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 239000008267 milk Substances 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
- 201000005115 pasteurellosis Diseases 0.000 description 3
- 201000006509 pleuropneumonia Diseases 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 241000193738 Bacillus anthracis Species 0.000 description 2
- 208000007198 Bovine Brucellosis Diseases 0.000 description 2
- 241000193155 Clostridium botulinum Species 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- 208000004232 Enteritis Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 244000199885 Lactobacillus bulgaricus Species 0.000 description 2
- 241000186673 Lactobacillus delbrueckii Species 0.000 description 2
- 241000186606 Lactobacillus gasseri Species 0.000 description 2
- 241000186604 Lactobacillus reuteri Species 0.000 description 2
- 241000186869 Lactobacillus salivarius Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 241000588769 Proteus <enterobacteria> Species 0.000 description 2
- 206010039438 Salmonella Infections Diseases 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 241000186064 Trueperella pyogenes Species 0.000 description 2
- 206010013023 diphtheria Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000002949 hemolytic effect Effects 0.000 description 2
- 244000000010 microbial pathogen Species 0.000 description 2
- 238000009629 microbiological culture Methods 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 244000144977 poultry Species 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 206010039447 salmonellosis Diseases 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 201000008827 tuberculosis Diseases 0.000 description 2
- 108020004465 16S ribosomal RNA Proteins 0.000 description 1
- 241000589291 Acinetobacter Species 0.000 description 1
- 241000186361 Actinobacteria <class> Species 0.000 description 1
- 241000272525 Anas platyrhynchos Species 0.000 description 1
- 244000118350 Andrographis paniculata Species 0.000 description 1
- 241000272814 Anser sp. Species 0.000 description 1
- 201000008283 Atrophic Rhinitis Diseases 0.000 description 1
- 241000193755 Bacillus cereus Species 0.000 description 1
- 108010001478 Bacitracin Proteins 0.000 description 1
- 201000001178 Bacterial Pneumonia Diseases 0.000 description 1
- 206010004016 Bacterial diarrhoea Diseases 0.000 description 1
- 241000606125 Bacteroides Species 0.000 description 1
- 241000186018 Bifidobacterium adolescentis Species 0.000 description 1
- 241001134770 Bifidobacterium animalis Species 0.000 description 1
- 241000186016 Bifidobacterium bifidum Species 0.000 description 1
- 241000186015 Bifidobacterium longum subsp. infantis Species 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- 101000782236 Bothrops leucurus Thrombin-like enzyme leucurobin Proteins 0.000 description 1
- 206010006049 Bovine Tuberculosis Diseases 0.000 description 1
- 241000589562 Brucella Species 0.000 description 1
- 241000589876 Campylobacter Species 0.000 description 1
- 206010051226 Campylobacter infection Diseases 0.000 description 1
- 241000606161 Chlamydia Species 0.000 description 1
- 206010008631 Cholera Diseases 0.000 description 1
- 208000014085 Chronic respiratory disease Diseases 0.000 description 1
- 241000064585 Clostridioides Species 0.000 description 1
- 241000193163 Clostridioides difficile Species 0.000 description 1
- 241000193468 Clostridium perfringens Species 0.000 description 1
- 241000193449 Clostridium tetani Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 102000000541 Defensins Human genes 0.000 description 1
- 108010002069 Defensins Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 241000194032 Enterococcus faecalis Species 0.000 description 1
- 201000000297 Erysipelas Diseases 0.000 description 1
- 241000605909 Fusobacterium Species 0.000 description 1
- 206010017711 Gangrene Diseases 0.000 description 1
- 241000606790 Haemophilus Species 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 208000032969 Hemorrhagic Septicemia Diseases 0.000 description 1
- 240000000691 Houttuynia cordata Species 0.000 description 1
- 235000013719 Houttuynia cordata Nutrition 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010022678 Intestinal infections Diseases 0.000 description 1
- 240000001046 Lactobacillus acidophilus Species 0.000 description 1
- 235000013956 Lactobacillus acidophilus Nutrition 0.000 description 1
- 235000013960 Lactobacillus bulgaricus Nutrition 0.000 description 1
- 244000199866 Lactobacillus casei Species 0.000 description 1
- 241000186840 Lactobacillus fermentum Species 0.000 description 1
- 240000002605 Lactobacillus helveticus Species 0.000 description 1
- 235000013967 Lactobacillus helveticus Nutrition 0.000 description 1
- 241000194036 Lactococcus Species 0.000 description 1
- 241001183079 Lactococcus lactis subsp. hordniae Species 0.000 description 1
- 206010024238 Leptospirosis Diseases 0.000 description 1
- 244000172809 Leuconostoc cremoris Species 0.000 description 1
- 241000192130 Leuconostoc mesenteroides Species 0.000 description 1
- 241000186779 Listeria monocytogenes Species 0.000 description 1
- 206010024641 Listeriosis Diseases 0.000 description 1
- 206010027249 Meningitis meningococcal Diseases 0.000 description 1
- 201000010924 Meningococcal meningitis Diseases 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 241000186362 Mycobacterium leprae Species 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 208000001572 Mycoplasma Pneumonia Diseases 0.000 description 1
- 201000008235 Mycoplasma pneumoniae pneumonia Diseases 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000192134 Oenococcus oeni Species 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 206010033971 Paratyphoid fever Diseases 0.000 description 1
- 208000014645 Pasteurella hemorrhagic septicemia Diseases 0.000 description 1
- 241000529920 Pediococcus parvulus Species 0.000 description 1
- 241000191996 Pediococcus pentosaceus Species 0.000 description 1
- 201000005702 Pertussis Diseases 0.000 description 1
- 206010035148 Plague Diseases 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 241000206469 Pulsatilla Species 0.000 description 1
- 206010039088 Rhinitis atrophic Diseases 0.000 description 1
- 241000606701 Rickettsia Species 0.000 description 1
- 206010039587 Scarlet Fever Diseases 0.000 description 1
- 241001552596 Scorzoneroides helvetica Species 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 206010058556 Serositis Diseases 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- 241000589970 Spirochaetales Species 0.000 description 1
- 241000194020 Streptococcus thermophilus Species 0.000 description 1
- 208000033809 Suppuration Diseases 0.000 description 1
- 208000024949 Swine Erysipelas Diseases 0.000 description 1
- 206010043376 Tetanus Diseases 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 208000037386 Typhoid Diseases 0.000 description 1
- 206010046793 Uterine inflammation Diseases 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 201000007691 actinomycosis Diseases 0.000 description 1
- 229940126575 aminoglycoside Drugs 0.000 description 1
- -1 aminoglycosides Chemical class 0.000 description 1
- 229960003071 bacitracin Drugs 0.000 description 1
- 229930184125 bacitracin Natural products 0.000 description 1
- CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- YBHILYKTIRIUTE-UHFFFAOYSA-N berberine Chemical compound C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 YBHILYKTIRIUTE-UHFFFAOYSA-N 0.000 description 1
- 229940093265 berberine Drugs 0.000 description 1
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 201000004927 campylobacteriosis Diseases 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 208000001848 dysentery Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 229940039695 lactobacillus acidophilus Drugs 0.000 description 1
- 229940004208 lactobacillus bulgaricus Drugs 0.000 description 1
- 229940012969 lactobacillus fermentum Drugs 0.000 description 1
- 229940054346 lactobacillus helveticus Drugs 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 229940041028 lincosamides Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 229940041033 macrolides Drugs 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 235000021243 milk fat Nutrition 0.000 description 1
- 239000006872 mrs medium Substances 0.000 description 1
- 230000021597 necroptosis Effects 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 210000003200 peritoneal cavity Anatomy 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
- 235000018291 probiotics Nutrition 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 150000007660 quinolones Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940040944 tetracyclines Drugs 0.000 description 1
- 201000008297 typhoid fever Diseases 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 239000000273 veterinary drug Substances 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
Classifications
-
- 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
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
本发明涉及一种灭活乳酸菌在防治细菌性疾病中的新用途，属于生物医药领域。这种药物的主要成分是灭活乳酸菌，可以通过将活的乳酸菌经过常规方法灭活制备。灭活乳酸菌静脉给药可以用于人或动物的各种细菌性疾病的预防、治疗或辅助治疗，具有广阔的应用前景。
Description
技术领域
本发明属于生物医药领域，尤其涉及灭活乳酸菌在防治细菌性疾病中的新用途。
背景技术
细菌性疾病对人和动物危害巨大。在临床上各种病原微生物常引起人和动物的呼吸道、消化道、内脏器官和皮肤等感染，使机体出现炎症反应、出血、化脓和组织坏死等病理损伤，严重时发生败血症、脓毒症、感染性休克和死亡。人医临床上发生的细菌性疾病包括：伤寒、霍乱、痢疾、肺结核、猩红热、百日咳、布鲁氏菌病、流行性脑脊髓膜炎、白喉、鼠疫、炭疽等。兽医临床上发生的细菌性疾病有：马接触传染性子宫炎、马鼻疽、马腺疫、马破伤风、牛生殖器弯曲杆菌病、牛大肠杆菌病、牛结核病、牛布氏杆菌病、牛出血性败血病、奶牛乳房炎、奶牛子宫内膜炎、牛传染性胸膜肺炎、牛放线菌病、羊梭菌病、羊快疫、羊猝狙、羊布氏杆菌病、羊接触染性胸膜肺炎、羊巴氏杆菌病、羊沙门氏菌病、猪水肿病、仔猪黄痢、仔猪白痢、猪副伤寒、猪巴氏杆菌病、猪丹毒、猪传染性萎缩性鼻炎、猪链球菌病、猪李氏杆菌病、猪传染性胸膜肺炎、猪梭菌性肠炎、猪增生性肠炎、猪副嗜血杆菌病、猪支原体肺炎、禽巴氏杆菌病、鹅霍乱、鸭传染性浆膜炎、鸭传染性窦炎、鸡大肠杆菌病、鸡沙门氏菌病、鸡传染性鼻炎、鸡慢性呼吸道病、犬钩端螺旋体病、犬布氏杆菌病、犬副伤寒、犬弯杆菌病、犬肉毒梭菌病、犬细菌性腹泻、犬细菌性肺炎等。以上可以看出细菌性疾病种类繁多，而且一些细菌病发病率也较高。
目前针对细菌性疾病主要通过抗菌药治疗，如β-内酰胺类、氨基糖苷类、四环素类、氯霉素类、大环内脂类、林可胺类、多肽类、喹诺酮类等。另外，中药及其提取物在细菌性疾病治疗中也经常使用，如黄连素片、鱼腥草注射液、穿心莲注射液、四黄止泻颗粒、白头翁散、杨树花口服液等用于人和畜禽细菌性疾病防治。此外，发现一些生物制剂也具有一定的抗菌作用，如杆菌肽、溶菌酶、防御素、噬菌体等。针对肠道感染的一些细菌性疾病，还可以通过口服益生菌(如乳酸菌)或乳酸菌提取物(如乳酸菌素)进行防治。虽然目前临床上抗菌类药物种类较多，但细菌耐药性问题仍面临严重挑战。一些细菌性疾病由于细菌耐药性问题而治愈难度大，如人结核病、奶牛乳房炎、鸡大肠杆菌病等。全球范围内超级耐药菌不断产生，给临床治疗带来极大困难。
因此，寻找新的应对细菌性疾病的药物非常重要。本发明发现将灭活乳酸菌进行静脉给药可以达到有效防治细菌性疾病的目的。这是一种全新的可用于细菌性疾病防治的药物，未来具有广阔的应用前景。这种药物未来可能用于耐药性致病菌的防治。
发明内容
本发明提供了一种全新的可以用于细菌性疾病防治的灭活乳酸菌混悬液，这种药物的主要成分为灭活的乳酸菌。该药物通过静脉给药可以有效防治细菌性疾病。
灭活乳酸菌在制备防治细菌性疾病药物中的用途，其特征在于，对所述的灭活乳酸菌进行革兰氏染色，在油镜下观察，灭活乳酸菌保持完整菌体形态，药物的给药方式为注射给药。此处所述的保持完整菌体形态是指与灭活前活菌菌体的轮廓和形态基本一致。所说的基本一致实质上是指乳酸菌灭活过程中菌体细胞壁可能会出现轻微变化，比如部分表面成分的流失，但这种变化微乎其微或很少发生。
灭活乳酸菌为一种或两种以上灭活乳酸菌混合物。所述的每单位剂量药物中包含灭活乳酸菌完整菌体数量为105—1012个。所述的注射给药为静脉注射给药。
所述乳酸菌包括：(1)乳杆菌属：德氏乳杆菌(L.delbrueckii)、保加利亚乳杆菌(L.bulgaricus)、瑞士乳杆菌(L.helviticus)、嗜酸乳杆菌(L.acidophlus)、格氏乳杆菌(L.gasseri)、唾液乳杆菌(L.salivarius)、植物乳杆菌(L.plantarum)、罗伊氏乳杆菌(L.reuteri)、短乳杆菌(L.brevis)、干酪乳杆菌(L.casei)、发酵乳杆菌(L.fementi)等；(2)片球菌属：如乳酸片球菌(P.acidi1actic)、戊糖片球菌(P.pentasiaceus)、小片球菌(P.parvulus)等；(3)明串球菌属：肠膜明串球菌(L.mesenteroides)及其乳脂亚种(L.cremoris)和葡聚糖亚种(Leuc.dextranicun)、乳酸明串球菌(L.lactis)、酒明串球菌(L.oenos)等；(4)肠球菌属：屎肠球菌(E.faecium)、粪肠球菌(E.faecalis)等；(5)乳球菌属：乳酸乳球菌乳酸亚种(L.lactis subsp.lactis)、乳酸乳球菌乳脂亚种(L.lactissubsp.cremoris)、乳酸乳球菌叶蝉亚种(L.lactis subsp.hordniae)等；(6)链球菌属：乳酸链球菌(S.lactis)、丁二酮乳酸链球菌(S.diacetilactis)、乳酪链球菌(S.creamoris)、嗜热乳链球菌(S.thermophilus)等；(7)双歧杆菌属：两歧双歧杆菌(B.bifidum)、长双歧杆菌(B.longum)、短双歧杆菌(B.breve)、婴儿双歧杆菌(B.infantis)、青春双歧杆菌(B.adolescentis)、动物双歧杆菌(B.animalis)等；(8)其他种属的乳酸菌。
优选的，乳酸菌选自乳酸乳球菌乳酸亚种(拉丁名称：Lactococcus lactissubsp.Lactis，保藏编号：CICC 6246)、植物乳杆菌植物亚种(拉丁名称：Lactobacillusplantarum subsp.Plantarum，保藏编号：CICC 6240)、长双歧杆菌(拉丁名称：Bifidobacterium longum，保藏编号：CICC 6196)、短乳杆菌(拉丁名称：Lactobacillusbrevis，保藏编号：CICC 6239)、屎肠球菌(拉丁名称：Enterococcus faecium，保藏编号：CICC 6049)。
用于本发明的制备灭活乳酸菌混悬液的方法包括：包括高温高压灭活、紫外线灭活、化学试剂灭活、辐射灭活等。
用于本发明的制备灭活乳酸菌静脉给药的剂型包括：粉针剂、混悬注射剂等各种剂型。用于本发明的灭活乳酸菌混悬液的给药方式包括：静脉推注和静脉滴注等。
本发明从中国工业微生物菌种保藏管理中心(CICC)购买了3种乳酸菌，分别是：乳酸乳球菌乳酸亚种(拉丁名称：Lactococcus lactis subsp.Lactis，保藏编号：CICC6246)、植物乳杆菌植物亚种(拉丁名称：Lactobacillus plantarum subsp.Plantarum，保藏编号：CICC 6240)、长双歧杆菌(拉丁名称：Bifidobacterium longum，保藏编号：CICC6196)，又自行分离鉴定得到了2种乳酸菌，分别是：短乳杆菌和屎肠球菌。分别对以上5种乳酸菌进行常规方法灭活，然后对小鼠尾静脉给药，发现以上5种灭活乳酸菌及混合物经静脉给药均可有效地降低致病菌对小鼠的致死率。此后，选择了分离得到的屎肠球菌又进行了详细研究，发现灭活的屎肠球菌仍然可以进行革兰氏染色，油镜下观察灭活的屎肠球菌与活的屎肠球菌保持一致的菌体轮廓和形态。然后对灭活屎肠球菌生理盐水混悬液进行离心，弃上清留沉淀，提取DNA，采用PCR技术仍可以扩增出16S rDNA基因片段，通过测序还可以进行乳酸菌种类鉴别。进一步开展了灭活屎肠球菌对小鼠尾静脉给药对致病菌感染的预防性和治疗性实验，发现无论预防性给药和还是治疗性给药，均可有效降低小鼠死亡数。另外，还发现灭活乳酸菌静脉给药对奶牛的乳房炎和子宫内膜炎也有效。以上说明，灭活乳酸菌混悬液对致病菌感染具有良好的防治作用。
本发明的灭活乳酸菌混悬液可以用于各种病原微生物引起的感染性疾病的防治，包括：(1)所有具有致病作用的革兰氏阳性菌，如金黄色葡萄球菌、溶血链球菌、肺炎球菌、炭疽杆菌、蜡样杆菌、破伤风杆菌、产气荚膜杆菌、肉毒杆菌、难辨梭菌、李斯特杆菌、魏氏梭菌、丹毒杆菌、化脓棒状杆菌等；(2)所有具有致病作用的革兰氏阴性菌，如脑膜炎球菌、淋球菌、不动杆菌、绿脓杆菌、百日咳杆菌、布氏杆菌、大肠杆菌、沙门氏菌、志贺氏菌、变形杆菌、白喉杆菌、结核杆菌、麻风杆菌等；(3)其他致病菌还包括螺旋体、支原体、立克次氏体、衣原体和放线菌等。
静脉注射灭活乳酸菌防治细菌性疾病的机制目前尚不完全清楚，推测可能的机制是：灭活乳酸菌静脉给药，可能与致病菌发生相互作用，阻断致病菌感染组织器官；也可能灭活乳酸菌静脉给药后经机体代谢产生了抗菌物质；或者灭活乳酸菌静脉给药后可激活机体免疫系统，间接发挥抗菌作用等。
附图说明
图1奶牛患乳房炎照片
图2灭活乳酸菌静脉给药后症状明显减轻照片
具体实施方式
实施例1
将屎肠球菌(购于中国工业微生物菌种保藏管理中心，拉丁名称：Enterococcusfaecium，保藏编号：CICC 6049)接种于MRS培养基，于37℃温箱培养24小时，然后3000转离心5分钟，去除上层培养液保留沉淀，加入无菌生理盐水清洗沉淀，离心5分钟，重复清洗3次后，加入无菌生理盐水，与沉淀混匀。取一定量的屎肠球菌生理盐水混悬液，于分光光度计690nm处测量其OD值，当用无菌生理盐水稀释的最终浓度的OD值为0.38时，将这样稀释浓度的屎肠球菌生理盐水混悬液作为1倍(1×)浓度，经过THOMA细菌计数板进行细菌计数测定该浓度下每mL混悬液中含有约108个屎肠球菌菌体。取少量的1×浓度的屎肠球菌生理盐水混悬液，进行革兰氏染色，在油镜下观察活菌的形态。此后将配制好的1×浓度的屎肠球菌生理盐水混悬液于121℃、压力0.12MPa，灭活15min，得到灭活屎肠球菌混悬液，取少量灭活屎肠球菌混悬液进行革兰氏染色，在油镜下观察灭活菌体的形态，发现灭活乳酸菌保持完整菌体形态，与其灭活前活菌菌体轮廓和形态一致，细菌计数发现灭活前后菌体数量没有明显变化。
实施例2
使用实施例1制备的1×浓度的灭活屎肠球菌混悬液，检测灭活屎肠球菌混悬液预防给药对沙门氏菌感染小鼠致死作用的影响。将体重为18-22g的清洁级昆明种小白鼠分为3组，即正常对照组、沙门氏菌组和灭活屎肠球菌组，每组30只小鼠，雌雄各半。正常对照组和沙门氏菌组的小鼠尾静脉注射无菌生理盐水，灭活屎肠球菌组尾静脉注射1×浓度的灭活屎肠球菌混悬液，给药体积均为0.1mL/10g。给药1次后间隔24小时，沙门氏菌组和灭活屎肠球菌组的小鼠分别尾静脉注射肠炎沙门氏菌(购于中国兽医微生物菌种保藏管理中心，拉丁名称：Salmonella enteritidis,保藏编号CVCC 3377)。连续观察7天，记录小鼠每天的死亡数。采用SPSS 11.5软件对实验数据进行卡方检验，结果见表1。由表1可知，与沙门氏菌对照组比较，灭活屎肠球菌组极显著地降低了小鼠的死亡数。说明灭活屎肠球菌静脉给药对沙门氏菌感染小鼠具有预防作用。
表1灭活屎肠球菌静脉给药预防沙门氏菌对小鼠致死作用的结果
注：**表示与正常对照组比较差异极显著P＜0.01，*表示与正常对照常组比较差异显著P＜0.05；△△表示与沙门氏菌组比较差异极显著P＜0.01，△表示与沙门氏菌组比较差异显著P＜0.05。
实施例3
使用实施例1制备1×浓度的灭活屎肠球菌混悬液，开展灭活屎肠球菌静脉给药治疗沙门氏菌感染小鼠作用的研究。将体重为18-22g的清洁级昆明种小白鼠分为3组，即正常对照组、沙门氏菌组和灭活屎肠球菌组，每组30只小鼠，雌雄各半。沙门氏菌组和灭活屎肠球菌组的小鼠腹腔注射肠炎沙门氏菌(购于中国兽医微生物菌种保藏管理中心，拉丁名称：Salmonella enteritidis，保藏编号CVCC 3377)。灭活屎肠球菌组在小鼠腹腔接种肠炎沙门氏菌后，立即尾静脉注射1×浓度的灭活屎肠球菌混悬液；正常对照组和沙门氏菌组的小鼠立即尾静脉注射无菌生理盐水，各组给药体积均为0.1mL/10g。第一次给药后间隔6小时，再进行第二次给药。此后连续观察7天，记录各组小鼠每天的死亡数。采用SPSS 11.5软件对实验数据进行卡方检验，结果见表2。由表2可知，与沙门氏菌组相比较，灭活屎肠球菌组极显著地降低了小鼠死亡数。以上说明，灭活屎肠球菌静脉给药对沙门氏菌感染的小鼠具有治疗作用。
表2灭活屎肠球菌静脉给药治疗沙门氏菌对小鼠致死作用的结果
注：**表示与正常对照组比较差异极显著P＜0.01，*表示与正常对照常组比较差异显著P＜0.05；△△表示与沙门氏菌组比较差异极显著P＜0.01，△表示与沙门氏菌比较差异显著P＜0.05。
实施例4
本发明从中国工业微生物菌种保藏管理中心(CICC)购买了5种乳酸菌，分别是：乳酸乳球菌乳酸亚种(拉丁名称：Lactococcus lactis subsp.Lactis，保藏编号：CICC6246)、植物乳杆菌植物亚种(拉丁名称：Lactobacillus plantarum subsp.Plantarum，保藏编号：CICC 6240)、长双歧杆菌(拉丁名称：Bifidobacterium longum，保藏编号：CICC6196)、短乳杆菌(拉丁名称：Lactobacillus brevis，保藏编号：CICC 6239)、屎肠球菌(拉丁名称：Enterococcus faecium，保藏编号：CICC 6049)。根据实施例1的方法分别制备上述5种乳酸菌的1×浓度的灭活乳酸菌混悬液，检测这5种灭活乳酸菌及混合物静脉给药对沙门氏菌感染小鼠致死作用的影响。将体重为18-22g的清洁级昆明种小白鼠分为正常对照组、沙门氏菌组、灭活乳酸乳球菌乳酸亚种组、灭活植物乳杆菌植物亚种组、灭活长双歧杆菌组、灭活短乳杆菌组、灭活屎肠球菌组、2种灭活乳酸菌混合组(即灭活屎肠球菌和灭活短乳杆菌等比例混合组)，每组30只小鼠，雌雄各半。正常对照组和沙门氏菌组的小鼠尾静脉注射无菌生理盐水，5种灭活乳酸菌组和2种灭活乳酸菌混合组分别尾静脉注射1×浓度的相应灭活乳酸菌混悬液和1×浓度的2种灭活乳酸菌混合的混悬液，给药体积均为0.1mL/10g。以上各组小鼠给药一次后间隔24小时，除正常对照组外，其他各组小鼠分别尾静脉注射肠炎沙门氏菌(购于中国兽医微生物菌种保藏管理中心，拉丁名称：Salmonellaenteritidis,保藏编号CVCC 3377)。连续观察7天，记录各组小鼠每天的死亡数。采用SPSS11.5软件对实验数据进行卡方检验，结果见表3。由表3可知，与沙门氏菌组相比较，5种灭活乳酸菌组和2种灭活乳酸菌混合组均显著或极显著地降低了小鼠死亡率。说明灭活乳酸菌静脉给药对肠炎沙门氏菌感染的小鼠具有保护作用。
表3五种灭活乳酸菌及混合物静脉给药对沙门氏菌致死小鼠的保护作用结果
注：**表示与正常对照组比较差异极显著P＜0.01，*表示与正常对照常组比较差异显著P＜0.05；△△表示与沙门氏菌组比较差异极显著P＜0.01，△表示与沙门氏菌组比较差异显著P＜0.05。
实施例5
某奶牛场，奶牛患乳房炎，主要由金黄色葡萄球菌、链球菌、大肠杆菌、支原体等致病菌感染引起。该患病奶牛的奶乳汁有絮状物质(参见附图1)，已用过几个兽药厂的抗菌药治疗无明显效果。按照实施例1方法和使用的屎肠球菌制备20×浓度的灭活屎肠球菌混悬液，给该患病奶牛静脉推注了22毫升，第二天又推注了20毫升。发现用药两天后乳腺炎症状明显减轻，牛奶絮状物消失，手摸肿块变软，肿区变小(参见附图2)。
实施例6
某奶牛场，奶牛患子宫内膜炎，主要由化脓性放线菌、坏死梭杆菌、拟杆菌、大肠杆菌、溶血性链球菌、变形杆菌、假单胞菌、梭状芽孢杆菌等致病菌感染引起，该患病奶牛子宫内充满炎性分泌物且自动流出。使用与实施例1相同的方法制备20×浓度的灭活植物乳杆菌植物亚种混悬液，给奶牛颈静脉推注25毫升，第二天又推注了25毫升。发现用药3天后不见炎性分泌物流出，经手掏才有一些炎性分泌物，已经大大减少，由此可见效果明显。
Claims (10)
1.灭活乳酸菌在制备防治细菌性疾病药物中的用途，其特征在于，对所述的灭活乳酸菌进行革兰氏染色，在油镜下观察，灭活乳酸菌保持完整菌体形态，药物可制成混悬液或粉针剂，给药方式为注射给药。
2.根据权利要求1的用途，其特征在于，所述的乳酸菌选自乳杆菌属、肠球菌属、乳球菌属、双歧杆菌属、明串球菌属、链球菌属。
3.根据权利要求1所述的用途，其特征在于，所述乳酸菌选自乳酸乳球菌乳酸亚种(拉丁名称：Lactococcus lactis subsp.Lactis，保藏编号：CICC 6246)、植物乳杆菌植物亚种(拉丁名称：Lactobacillus plantarum subsp.Plantarum，保藏编号：CICC 6240)、长双歧杆菌(拉丁名称：Bifidobacterium longum，保藏编号：CICC 6196)、短乳杆菌(拉丁名称：Lactobacillus brevis，保藏编号：CICC 6239)、屎肠球菌(拉丁名称：Enterococcusfaecium，保藏编号：CICC 6049)。
4.如权利要求1所述的用途，其特征在于，灭活乳酸菌为一种或两种以上灭活乳酸菌混合物。
5.根据权利要求1所述的用途，其特征在于，利用高温高压灭活、紫外线灭活、化学试剂灭活或辐射灭活中的任一种灭活方法得到所述灭活乳酸菌。
6.根据权利要求1-5任一项所述的用途，其特征在于，所述的注射给药为静脉注射给药。
7.根据权利要求6所述的用途，其特征在于，注射时，每ml剂量药物中包含灭活乳酸菌完整菌体数量为105—1012个。
8.根据权利要求1-7任一项所述的用途，其特征在于，所述防治细菌性疾病药物可以制成粉针剂或混悬注射剂。
9.根据权利要求8所述的注射剂，其特征在于，所述的注射剂按照如下方法制备而成：将乳酸菌进行常规液体培养基培养12-36小时后，3000-5000转离心保留沉淀，再将沉淀充分清洗后，配制成所需浓度混悬液，于120-122℃、压力0.1-0.2MPa，灭活15-30min得到灭活乳酸菌注射剂。
10.根据权利要求1-7任一项所述的用途，其特征在于，所述的细菌性疾病包括：革兰氏阳性菌和具有致病作用的革兰氏阴性菌感染导致的疾病。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610809582.7A CN107802652B (zh) | 2016-09-08 | 2016-09-08 | 灭活乳酸菌在防治细菌性疾病药物中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610809582.7A CN107802652B (zh) | 2016-09-08 | 2016-09-08 | 灭活乳酸菌在防治细菌性疾病药物中的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107802652A true CN107802652A (zh) | 2018-03-16 |
| CN107802652B CN107802652B (zh) | 2020-08-25 |
Family
ID=61576075
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610809582.7A Active CN107802652B (zh) | 2016-09-08 | 2016-09-08 | 灭活乳酸菌在防治细菌性疾病药物中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107802652B (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112704153A (zh) * | 2020-12-22 | 2021-04-27 | 江苏省协同医药生物工程有限责任公司 | 一种免疫缺陷鼠饲料及其制备方法 |
| CN113230283A (zh) * | 2021-04-01 | 2021-08-10 | 石河子大学 | 一种鸡大肠杆菌治疗性微生态制剂及其制备与应用 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101612169A (zh) * | 2008-06-27 | 2009-12-30 | 生物源生物技术（深圳）有限公司 | 灭活的乳酸菌微生态制剂及其制备方法 |
| CN102725397A (zh) * | 2010-11-04 | 2012-10-10 | 细胞生物技术公司 | 用于抗菌的死乳酸菌菌体及其制备方法 |
| CN104906143A (zh) * | 2015-05-19 | 2015-09-16 | 清远海贝生物技术有限公司 | 一种灭活的乳酸菌液体制剂及其制备方法 |
| CN106307549A (zh) * | 2016-08-17 | 2017-01-11 | 江苏微康生物科技有限公司 | 灭活型乳酸菌微生态制剂及其制备方法和应用 |
-
2016
- 2016-09-08 CN CN201610809582.7A patent/CN107802652B/zh active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101612169A (zh) * | 2008-06-27 | 2009-12-30 | 生物源生物技术（深圳）有限公司 | 灭活的乳酸菌微生态制剂及其制备方法 |
| CN102725397A (zh) * | 2010-11-04 | 2012-10-10 | 细胞生物技术公司 | 用于抗菌的死乳酸菌菌体及其制备方法 |
| CN104906143A (zh) * | 2015-05-19 | 2015-09-16 | 清远海贝生物技术有限公司 | 一种灭活的乳酸菌液体制剂及其制备方法 |
| CN106307549A (zh) * | 2016-08-17 | 2017-01-11 | 江苏微康生物科技有限公司 | 灭活型乳酸菌微生态制剂及其制备方法和应用 |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112704153A (zh) * | 2020-12-22 | 2021-04-27 | 江苏省协同医药生物工程有限责任公司 | 一种免疫缺陷鼠饲料及其制备方法 |
| CN112704153B (zh) * | 2020-12-22 | 2023-06-06 | 江苏省协同医药生物工程有限责任公司 | 一种免疫缺陷鼠饲料及其制备方法 |
| CN113230283A (zh) * | 2021-04-01 | 2021-08-10 | 石河子大学 | 一种鸡大肠杆菌治疗性微生态制剂及其制备与应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107802652B (zh) | 2020-08-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Jiménez et al. | Oral administration of Lactobacillus strains isolated from breast milk as an alternative for the treatment of infectious mastitis during lactation | |
| WO2017020784A1 (zh) | 一种脆弱拟杆菌及其应用 | |
| Zhang et al. | Screening and evaluation of lactic acid bacteria with probiotic potential from local Holstein raw milk | |
| CN112877233B (zh) | 一种瑞士乳杆菌菌株及其应用 | |
| CN1272791A (zh) | 包含鼠李糖乳杆菌的药物制剂 | |
| WO2017071346A1 (zh) | 脆弱拟杆菌在抗水产病原菌中的应用 | |
| ES2331650T3 (es) | Utilizacion de bacterias probioticas en el tratamiento de una infeccion. | |
| CN117143785B (zh) | 一株片球菌及其应用 | |
| Gao et al. | A new Lactobacillus gasseri strain HMV18 inhibits the growth of pathogenic bacteria | |
| Enany et al. | In vitro antagonistic activity of Lactobacillus casei against Helicobacter pylori | |
| CN116426406B (zh) | 一种唾液联合乳杆菌dy802及其应用 | |
| CN112353822A (zh) | 一种乳酸乳球菌粒子与益生菌在制备抗幽门螺旋杆菌感染药物中的应用 | |
| CN116790402A (zh) | 一株具有抗炎特性的单形拟杆菌菌株、培养方法及应用 | |
| CN107802652B (zh) | 灭活乳酸菌在防治细菌性疾病药物中的应用 | |
| MX2012012372A (es) | Prevencion y tratamiento de infeccion gastrointestinal en mamiferos. | |
| CN101492650B (zh) | 一种抗猪链球菌细菌素及其生产方法与专用菌株 | |
| CN118006506A (zh) | 一种犬源罗伊氏乳杆菌、菌剂及其应用 | |
| WO2017020783A1 (zh) | 脆弱拟杆菌在预防和/或治疗脑膜炎中的应用 | |
| CN114874952B (zh) | 干酪乳杆菌hjd及其应用 | |
| JP6005041B2 (ja) | プレバイオティック組成物の製造のための大豆発酵抽出物の使用 | |
| CN107802657A (zh) | 灭活乳酸菌在防治猪病毒性疾病药物中的应用 | |
| Gu et al. | Effects of TCMs and Lactobacillus strains on immunosuppressed mice and bacteriostatic effect on Escherichia coli K88 after fermentation | |
| Yang et al. | The probiotic attributes and anti-pseudorabies virus evaluation of Lactobacillus isolates | |
| CN107802654A (zh) | 灭活乳酸菌在防治牛细菌性疾病药物中的应用 | |
| Li et al. | Probiotic properties of E nterococcus strains isolated from the silage |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |