WO2020039443A1 - Compositions and methods for controlling mammalian pathogens - Google Patents
Compositions and methods for controlling mammalian pathogens Download PDFInfo
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- WO2020039443A1 WO2020039443A1 PCT/IL2019/050942 IL2019050942W WO2020039443A1 WO 2020039443 A1 WO2020039443 A1 WO 2020039443A1 IL 2019050942 W IL2019050942 W IL 2019050942W WO 2020039443 A1 WO2020039443 A1 WO 2020039443A1
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- HELXLJCILKEWJH-UHFFFAOYSA-N entered according to Sigma 01432 Natural products C1CC2C3(C)CCCC(C)(C(=O)OC4C(C(O)C(O)C(CO)O4)O)C3CCC2(C2)CC(=C)C21OC(C1OC2C(C(O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O HELXLJCILKEWJH-UHFFFAOYSA-N 0.000 description 1
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- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 238000011160 research Methods 0.000 description 1
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- 239000011780 sodium chloride Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- QFVOYBUQQBFCRH-VQSWZGCSSA-N steviol Chemical compound C([C@@]1(O)C(=C)C[C@@]2(C1)CC1)C[C@H]2[C@@]2(C)[C@H]1[C@](C)(C(O)=O)CCC2 QFVOYBUQQBFCRH-VQSWZGCSSA-N 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/105—Aliphatic or alicyclic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/142—Amino acids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/30—Feeding-stuffs specially adapted for particular animals for swines
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/60—Feeding-stuffs specially adapted for particular animals for weanlings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- 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
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- the present disclosure relates to compositions and methods for controlling pathogens in mammalian subjects. More particularly, the current invention pertains to a composition and method for reduction of pathogenic bacteria by oral administration of a non- antibiotic isotonic drink.
- Pigs coexist with a diverse and dense commensal microbiota in their gastrointestinal tract. Most of these microbes are beneficial, providing necessary nutrients or protection against harmful pathogens for the host.
- the microbial colonization of the porcine intestine begins at birth and follows a rapid succession during the neonatal and weaning period.
- the intestinal immune system of the newborn piglet is poorly developed at birth and undergoes a rapid period of expansion and specialization that is not achieved before early (commercial-) weaning.
- the animal agriculture sector is a major user of antibiotic drugs for disease treatment, disease control, disease prevention, and“production purposes” (such as growth promotion).
- FIG.l depicting a graphical presentation of a preferred embodiment of the current invention.
- FIG.2 depicting yet another graphical presentation of a preferred embodiment of the current invention.
- composition useful for an antibiotic- free composition for control of pathogens in a mammalian subject characterized by at least three members of a group consisting of steviol glycoside, citric acid monohydrate, monosodium glutamate, glycine, mixtures and derivatives thereof.
- compositions as defined in any of the above wherein said composition is an oral isotonic composition characterized by no residual chlorine taste.
- composition as defined in any of the above, wherein said control is reduction in counts of said pathogens in said mammalian subject compared to control mammalian subject.
- composition as defined in any of the above, wherein said control is elimination of said pathogens in said mammalian subject compared to control mammalian subject.
- compositions as defined in any of the above wherein said animal is selected from a group consisting at least one of human, cattle, pigs, sheep, goats, horses, mules, asses, buffalo, camels, chickens, turkeys, ducks, geese, guinea fowl, squabs, dogs, or cats of any age.
- Astrovirus Bacillus anthracis, Bacillus cereus, Bacillus subtilis, Bacteriodes fragilis, Bartonella quintana, Blastocystis hominis, Bordetella pertussis, Borrelia burgdorferi, Borrelia duttoni, Borrelia recurrentis, Brevundimonas diminuta, Brevundimonas vesicularisBrucella spp., Burkholderia cepacia (incl.
- Corynebacterium diphtheria Corynebacterium pseudotuberculosis, Corynebacterium spp., Corynebacterium ulcerans, Coxiella burnetii, Coxsackievirus, Crimean-Congo haemorrhagic fever virus, Cryptococcus neof ormans, Cryptosporidium hominis, Cryptosporidium parvum e, Cyclospora cayetanensisCytomegalovirus
- EHEC EHEC
- EPEC ETEC
- EIEC EAEC
- ESBL/MRGN DAEC
- Filarial worms Foot-and-mouth disease virus (FMDV)
- Francisella tularensis Giardia lamblia, Haemophilus influenza, Hantavirus, Helicobacter pylori, Helminths (Worms), Hepatitis A virus
- HAV Hepatitis B virus - HBV
- Hepatitis C virus - HCV Hepatitis D virus
- Hepatitis E virus Herpes simplex virus - HSV, Histoplasma capsulatum
- Human enterovirus 71 Human herpesvirus 6 (HHV-6), Human herpesvirus 7 (HHV-7), Human herpesvirus 8 (HHV-8), Human immunodeficiency virus - HIV, Human metapneumovirus, Human papillomavirus, Hymenolepsis nana, Influenza virus, Klebsiella granulomatis, Klebsiella oxytoca (incl. ESBL/MRGN), Klebsiella pneumoniae MDR (incl.
- ESBL/MRGN ESBL/MRGN
- Lassa virus Leclercia adecarboxylata, Legionella pneumophila, Leishmania spp., Leptospira interrogans, Leuconostoc pseudomesenteroides, Listeria monocytogenes, Marburg virus, Measles virus, Micrococcus luteus, Microsporum spp., Molluscipoxvirus, Morganella spp., Mumps virus, Mycobacterium chimaera Myco, Mycobacterium leprae Myco, Mycobacterium tuberculosis (incl.
- MDR Tuberculocidal, Mycoplasma genitalium, Mycoplasma pneumoniae, Neisseria meningitides, Neisseria gonorrhoeae, Norovirus, Opisthorchis viverrini, Orientia tsutsugamushi, Pantoea agglomerans, Paracoccus yeei, Parainfluenza virus, Parvovirus, Pediculus humanus capitis, Pediculus humanus corporis, Plasmodium spp., Pneumocystis jiroveci, Poliovirus, Polyomavirus, Prevotella spp., Propionibacterium species, Proteus mirabilis (incl.
- Proteus vulgaris Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa, Pseudomonas spp., Rabies virus, Ralstonia spp., Respiratory syncytial virus - RSV, Rhinovirus, Rickettsia prowazekii, Rickettsia typhi, Roseomonas gilardii, Rotavirus, Rubella virus, Schistosoma mansoni, Salmonella enteritidis, Salmonella paratyphi, Salmonella spp., Salmonella typhimurium, Sarcoptes scabiei (Itch mite), Sapovirus, Serratia marcescens (incl.
- ESBL/MRGN Shigella sonnei, Sphingomonas species, Spirochaetaceae (inc. Brachyspira hyodysenteriae), Staphylococcus aureus (incl. MRSA, VRSA), Staphylococcus capitis, Staphylococcus epidermidis (incl.
- MRSE Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus lugdunensis, Staphylococcus pasteuri, Staphylococcus saprophyticus, Stenotrophomonas maltophilia, Streptococcus pneumoniae, Streptococcus pyogenes (incl.
- PRSP Streptococcus spp.
- Strongyloides stercoralis Taenia solium, TBE virus, Toxoplasma gondii, Treponema pallidum, Trichinella spiralis, Trichomonas vaginalis, Trichophyton spp., Trichosporon spp., Trichuris trichiura, Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Vaccinia virus, Varicella zoster virus, Variola virus, Vibrio cholerae, West Nile virus (WNV), Yellow fever virus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudotuberculosis, Zika virus and any combination thereof.
- WNV West Nile virus
- Yellow fever virus Yersinia enterocolitica
- Yersinia pestis Yersinia pseudo
- pathogens are pathogenic bacteria, selected from a group consisting of bacteria families Actinomyces, Bacillus, Bartonella, Bordetella, Borrelia, Brucella, Campylobacter, Chlamydia, Clostridium, Corynebacterium, Enterococcus, Escherichia, Escherichia coli, Francisell, Haemophilus, Helicobacter, Helicobacter pylori, Legionella, Leptospira, Listeria, Mycobacterium, Mycoplasma, Neisseria, Prevotellaceae, Pseudomonas, Rickettsia, Salmonella, Shigella, Spirochaetaceae, Staphylococcus, Streptococcus, Treponema, Ureaplasma, Vibrio, Yersinia, and any combination thereof. It is another object of the present invention to
- compositions as defined in any of the above, wherein the composition is in the form selected from the group consisting of a tablet, a capsule, a pill, lyophilized, powder, emulsion, powder, cream, ointment, paste, lotion, gel, liquid, a solution, a patch, suspension, granulated powder, liquid, syrup, cream, foam, capsule, suppository, enema, infusion, enteric-coated pill, enteric-coated capsule, mouth wash, toothpaste, and any combination thereof.
- the composition is in the form selected from the group consisting of a tablet, a capsule, a pill, lyophilized, powder, emulsion, powder, cream, ointment, paste, lotion, gel, liquid, a solution, a patch, suspension, granulated powder, liquid, syrup, cream, foam, capsule, suppository, enema, infusion, enteric-coated pill, enteric-coated capsule, mouth wash, toothpaste, and any combination thereof.
- compositions as defined in any of the above, wherein said composition is configured to be administrable in a manner selected from a group consisting of fast release, slow release, sustained release, controlled release and any combination thereof.
- composition is an oral isotonic composition characterized by no residual chlorine taste.
- Astrovirus Bacillus anthracis, Bacillus cereus, Bacillus subtilis, Bacteriodes fragilis, Bartonella quintana, Blastocystis hominis, Bordetella pertussis, Borrelia burgdorferi, Borrelia duttoni, Borrelia recurrentis, Brevundimonas diminuta, Brevundimonas vesicularisBrucella spp., Burkholderia cepacia (incl.
- Corynebacterium diphtheria Corynebacterium pseudotuberculosis, Corynebacterium spp., Corynebacterium ulcerans, Coxiella burnetii, Coxsackievirus, Crimean-Congo haemorrhagic fever virus, Cryptococcus neof ormans, Cryptosporidium hominis, Cryptosporidium parvum e, Cyclospora cayetanensisCytomegalovirus
- EHEC EHEC
- EPEC ETEC
- EIEC EAEC
- ESBL/MRGN DAEC
- Filarial worms Foot-and-mouth disease virus (FMDV)
- Francisella tularensis Giardia lamblia, Haemophilus influenza, Hantavirus, Helicobacter pylori, Helminths (Worms), Hepatitis A virus
- HAV Hepatitis B virus - HBV
- Hepatitis C virus - HCV Hepatitis D virus
- Hepatitis E virus Herpes simplex virus - HSV, Histoplasma capsulatum
- Human enterovirus 71 Human herpesvirus 6 (HHV-6), Human herpesvirus 7 (HHV-7), Human herpesvirus 8 (HHV-8), Human immunodeficiency virus - HIV, Human metapneumovirus, Human papillomavirus, Hymenolepsis nana, Influenza virus, Klebsiella granulomatis, Klebsiella oxytoca (incl. ESBL/MRGN), Klebsiella pneumoniae MDR (incl.
- ESBL/MRGN ESBL/MRGN
- Lassa virus Leclercia adecarboxylata, Legionella pneumophila, Leishmania spp., Leptospira interrogans, Leuconostoc pseudomesenteroides, Listeria monocytogenes, Marburg virus, Measles virus, Micrococcus luteus, Microsporum spp., Molluscipoxvirus, Morganella spp., Mumps virus, Mycobacterium chimaera Myco, Mycobacterium leprae Myco, Mycobacterium tuberculosis (incl.
- MDR Tuberculocidal, Mycoplasma genitalium, Mycoplasma pneumoniae, Neisseria meningitides, Neisseria gonorrhoeae, Norovirus, Opisthorchis viverrini, Orientia tsutsugamushi, Pantoea agglomerans, Paracoccus yeei, Parainfluenza virus, Parvovirus, Pediculus humanus capitis, Pediculus humanus corporis, Plasmodium spp., Pneumocystis jiroveci, Poliovirus, Polyomavirus, Prevotella spp., Propionibacterium species, Proteus mirabilis (incl.
- Proteus vulgaris Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa, Pseudomonas spp., Rabies virus, Ralstonia spp., Respiratory syncytial virus - RSV, Rhinovirus, Rickettsia prowazekii, Rickettsia typhi, Roseomonas gilardii, Rotavirus, Rubella virus, Schistosoma mansoni, Salmonella enteritidis, Salmonella paratyphi, Salmonella spp., Salmonella typhimurium, Sarcoptes scabiei ( Itch mite), Sapovirus, Serratia marcescens (incl.
- ESBL/MRGN Shigella sonnei, Sphingomonas species, Spirochaetaceae (inc. Brachyspira hyodysenteriae ), Staphylococcus aureus (incl. MRSA, VRSA), Staphylococcus capitis, Staphylococcus epidermidis (incl.
- MRSE Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus lugdunensis, Staphylococcus pasteuri, Staphylococcus saprophyticus, Stenotrophomonas maltophilia, Streptococcus pneumoniae, Streptococcus pyogenes (incl.
- PRSP Streptococcus spp.
- Strongyloides stercoralis Taenia solium, TBE virus, Toxoplasma gondii, Treponema pallidum, Trichinella spiralis, Trichomonas vaginalis, Trichophyton spp., Trichosporon spp., Trichuris trichiura, Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Vaccinia virus, Varicella zoster virus, Variola virus, Vibrio cholerae, West Nile virus (WNV), Yellow fever virus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudotuberculosis, Zika virus and any combination thereof.
- WNV West Nile virus
- Yellow fever virus Yersinia enterocolitica
- Yersinia pestis Yersinia pseudo
- pathogens are pathogenic bacteria, selected from a group consisting of bacteria families Actinomyces, Bacillus, Bartonella, Bordetella, Borrelia, Brucella, Campylobacter, Chlamydia, Clostridium, Corynebacterium, Enterococcus, Escherichia, Escherichia coli, Francis ell, Haemophilus, Helicobacter, Helicobacter pylori, Legionella, Leptospira, Listeria, Mycobacterium, Mycoplasma, Neisseria, Prevotellaceae, Pseudomonas, Rickettsia, Salmonella, Shigella, Spirochaetaceae , Staphylococcus, Streptococcus, Treponema, Ureaplasma, Vibrio, Yersinia and any combination thereof.
- composition is in the form selected from the group consisting of a tablet, a capsule, a pill, lyophilized, powder, emulsion, powder, cream, ointment, paste, lotion, gel, liquid, a solution, a patch, suspension, granulated powder, liquid, syrup, cream, foam, capsule, suppository, enema, infusion, enteric-coated pill, enteric-coated capsule, mouth wash, toothpaste, and any combination thereof.
- composition is configured to be administrable in a manner selected from a group consisting of fast release, slow release, sustained release, controlled release and any combination thereof.
- livestock refers to domesticated animals raised in an agricultural setting to produce labor and commodities such as meat, eggs, milk, fur, leather, and wool. Livestock includes beef and dairy cattle, pigs, sheep, goats, horses, mules, asses, buffalo, alpaca and camels; as well as the raising of birds commercially for meat or eggs, i.e., chickens, turkeys, ducks, geese, guinea fowl, and squabs.
- pathogen generally refers hereinafter to biological agent or micro organism (microbe) capable of producing disease in the host; i.e. a pathogen or infectious agent is a biological agent that causes disease or illness to its host.
- Pathogen is a micro-organism that may be inter alia bacteria, viruses, fungi, prions, parasites, or protozoan.
- Pathogens comprise the following: Acinetobacter baumannii, Acinetobacter Iwoffii, Acinetobacter spp. (incl. MDR), Actinomycetes, Adenovirus, Aeromonas spp., Alcaligenes faecalis, Alcaligenes spp./Achromobacter spp. Alcaligenes xylosoxidans (incl. ESBL/MRGN), Arbovirus Virucidal, Ascaris lumbricoides, Aspergillus spp.
- Astrovirus Bacillus anthracis, Bacillus cereus, Bacillus subtilis, Bacteriodes fragilis, Bartonella quintana, Blastocystis hominis, Bordetella pertussis, Borrelia burgdorferi, Borrelia duttoni, Borrelia recurrentis, Brevundimonas diminuta, Brevundimonas vesicularisBrucella spp., Burkholderia cepacia (incl.
- Corynebacterium diphtheria Corynebacterium pseudotuberculosis, Corynebacterium spp.
- Corynebacterium ulcerans Coxiella burnetii, Coxsackievirus, Crimean-Congo haemorrhagic fever virus, Cryptococcus neoformans, Cryptosporidium hominis, Cryptosporidium parvum e, Cyclospora cayetanensisCytomegalovirus - CMV, Dengue virus, Dientamoeba fragilis, Ebola virus, Echinococcus spp,.
- Echovirus Entamoeba dispar, Entamoeba histolytica, Enterobacter aero genes, Enterobacter cloacae (incl. ESBL/MRGN), Enterobius vermicularis, Enterococcus faecalis (incl. VRE), Enterococcus faecium (incl. VRE), Enterococcus hirae, Epidermophyton spp. Epstein-Barr virus EBV, Escherichia coli (incl.
- EHEC EHEC
- EPEC ETEC
- EIEC EAEC
- ESBL/MRGN DAEC
- Filarial worms Foot-and-mouth disease virus
- FMDV Francisella tularensis
- Giardia lamblia Haemophilus influenza
- Hantavirus Helicobacter pylori
- Helminths Helminths (Worms)
- Hepatitis A virus - HAV Hepatitis B virus - HBV
- Hepatitis C virus - HCV Hepatitis D virus
- Hepatitis E virus Herpes simplex virus - HSV, Histoplasma capsulatum
- Human enterovirus 71 Human herpesvirus 6 (HHV-6), Human herpesvirus 7 (HHV-7), Human herpesvirus 8 (HHV-8), Human immunodeficiency virus - HIV, Human metapneumovirus, Human papillomavirus, Hymenolepsis nana, Influenza
- ESBL/MRGN Klebsiella pneumoniae MDR
- ESBL/MRGN Klebsiella pneumoniae MDR
- Lassa virus Leclercia adecarboxylata, Legionella pneumophila, Leishmania spp., Leptospira interrogans, Leuconostoc pseudomesenteroides, Listeria monocytogenes, Marburg virus, Measles virus, Micrococcus luteus, Microsporum spp., Molluscipoxvirus, Morganella spp., Mumps virus, Mycobacterium chimaera Myco, Mycobacterium leprae Myco, Mycobacterium tuberculosis (incl.
- MDR Tuberculocidal, Mycoplasma genitalium, Mycoplasma pneumoniae, Neisseria meningitides, Neisseria gonorrhoeae, Norovirus, Opisthorchis viverrini, Orientia tsutsugamushi, Pantoea agglomerans, Paracoccus yeei, Parainfluenza virus, Parvovirus, Pediculus humanus capitis, Pediculus humanus corporis, Plasmodium spp., Pneumocystis jiroveci, Poliovirus, Polyomavirus, Prevotella spp., Propionibacterium species, Proteus mirabilis (incl.
- Proteus vulgaris Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa, Pseudomonas spp., Rabies virus, Ralstonia spp., Respiratory syncytial virus - RSV, Rhinovirus, Rickettsia prowazekii, Rickettsia typhi, Roseomonas gilardii, Rotavirus, Rubella virus, Schistosoma mansoni, Salmonella enteritidis, Salmonella paratyphi, Salmonella spp., Salmonella typhimurium, Sarcoptes scabiei ( Itch mite), Sapovirus, Serratia marcescens (incl.
- ESBL/MRGN Shigella sonnei, Sphingomonas species, Spirochaetaceae (inc. Brachyspira hyodysenteriae ), Staphylococcus aureus (incl. MRSA, VRSA), Staphylococcus capitis, Staphylococcus epidermidis (incl.
- MRSE Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus lugdunensis, Staphylococcus pasteuri, Staphylococcus saprophyticus, Stenotrophomonas maltophilia, Streptococcus pneumoniae, Streptococcus pyogenes (incl.
- PRSP Streptococcus spp.
- Strongyloides stercoralis Taenia solium, TBE virus, Toxoplasma gondii, Treponema pallidum, Trichinella spiralis, Trichomonas vaginalis, Trichophyton spp., Trichosporon spp., Trichuris trichiura, Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Vaccinia virus, Varicella zoster virus, Variola virus, Vibrio cholerae, West Nile virus (WNV), Yellow fever virus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudotuberculosis, Zika virus.
- WNV West Nile virus
- Yellow fever virus Yersinia enterocolitica
- Yersinia pestis Yersinia pseudotuberculo
- pathogenic bacteria generally refers hereinafter to bacteria that can cause disease.
- a pathogenic bacterium comprises the following bacteria families: Actinomyces, Bacillus, Bartonella, Bordetella, Borrelia, Brucella, Campylobacter, Chlamydia, Clostridium, Corynebacterium, Enterococcus, Escherichia, Escherichia coli, Francis ell, Haemophilus, Helicobacter, Legionella, Leptospira, Listeria, Mycobacterium, Mycoplasma, Neisseria, Prevotellaceae, Pseudomonas, Rickettsia, Salmonella, Shigella, Spirochaetaceae, Staphylococcus, Streptococcus, Treponema, Ureaplasma, Vibrio, Yersinia.
- gut pathogens refers hereinafter to gastrointestinal pathogenic bacteria, viruses, fungi, prions, parasites, or protozoan, comprising inter alia bacteria of the following types: Escherichia Coli, Salmonella, Campylobacter, Virio cholera, Shigella, Clostridium pertingens, Bacillus cereus, and Yersnia entercolitica while pathogen viruses comprise inter alia rotavirus and small round viruses.
- steviol refers hereinafter to steviol glycoside, Rebaudioside A extract.
- the current invention discloses compositions and methods for controlling pathogens; eradicating, eliminating or reducing counts of pathogens in mammalian subjects.
- the current invention refers to the enterotrophic effect of an isotonic composition, Px, when administered to piglets during the first week of life and Px-gruel when administered in the immediate pre-and post- weaning period, resulting in significant reductions in intestinal E. coli load in the Px- administered piglets.
- compositions, products and formulations comprise or based on commercially available Px (trade mark) by Tonisity International Ltd, namely, a composition, e.g., defined below:
- Table 1 Ingredients of Px formulation.
- the composition consists of at least two members of a group consisting of steviol glycoside, citric acid monohydrate, monosodium glutamate and glycine, this composition characterized by that that the composition consists of at least three members of a group consisting of steviol glycoside, citric acid monohydrate, monosodium glutamate and glycine. Additionally or alternatively, this composition is characterized by that said composition consisting of steviol glycoside, citric acid monohydrate, monosodium glutamate and glycine.
- a total of 56 piglets were randomly selected from each litter for euthanasia at 9 and 17 days of age and a further 20 piglets were randomly selected from each treatment group at 30 days of age.
- Samples of small intestine and ingesta from each piglet were evaluated for differences in intestinal histomorphometry, thickness of intestinal mucus layer, semi-quantitative aerobic bacterial culture, and rotaviruses PCR at the University of Minnesota Veterinary Diagnostic Laboratory.
- Samples taken from the ileal mucosa of each piglet were also submitted for semiquantitative aerobic bacterial culture (E. coli). Table 3. Test Products
- Test product was given to the litters as follows:
- pans of Px was placed in each farrowing pen and filled once daily with 500 mL of solution per day.
- Px litters were given 2 lb/litter ( ⁇ 65 g/pig) of Px-gruel (made with a 3% solution) in an open pan, in the farrowing pen.
- Group A control pigs had 14/26 (54%) subjects positive for E. coli, with 4 pigs having positive results for beta-hemolytic E. coli.
- Group B pigs had 7/30 (23%) subjects positive for E. coli, with 1 pig having positive results for beta-hemolytic E. coli.
- Overall (preweaning and postweaning combined) pigs from Group B tended to have fewer pigs positive for E.
- ETEC Enterotoxigenic E. coli
- Example 2 fecal samples were collected from each pig for pathogen detection and analysis.
- the analysis included 16S rRNA gene sequencing.
- 16S rRNA gene sequencing was performed using the MiSeq (Illumina) platform after PCR amplification of the 16S v4 region. Data was normalized to the lowest number of reads per pig (3157), as the rarefaction curves revealed a plateau after this point.
- Prevotella have been previously associated with intestinal disturbances due to weaning stress in pigs and are known intestinal mucus degraders, See Gresse R, Chaucheyras- Durand F, Fleury MA et al. Gut microbiota dysbiosis in postweaning piglets: understanding the keys to health. Trends Microbiol Elsevier Current Trends, 2017;25:851-873, and Arumugam M, Raes J, Pelletier E et al. Enterotypes of the human gut microbiome. Nature Nature Publishing Group, 2011;473: 174-180.
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Abstract
The present disclosure concerns an antibiotic-free composition for control of pathogens in a mammalian subject, characterized by at least three members of a group consisting of steviol glycoside, citric acid monohydrate, monosodium glutamate, glycine, mixtures and derivatives thereof. The present disclosure concerns more particularly an antibiotic-free oral-administered isotonic composition for control of gut pathogens in mammals.
Description
COMPOSITIONS AND METHODS FOR CONTROLLING MAMMALIAN PATHOGENS
Field of the invention
The present disclosure relates to compositions and methods for controlling pathogens in mammalian subjects. More particularly, the current invention pertains to a composition and method for reduction of pathogenic bacteria by oral administration of a non- antibiotic isotonic drink.
Background of the invention
Early-life and weaning are associated with major shifts in the microbial community of the gut in both humans and other mammals. Of particular interest is the study of the gut microbiome, its evolution beginning in utero and across the lifespan, its effect on promotion of health, and its role in the development of disease; see Gritz, E. C., & Bhandari, V. (2015). The human neonatal gut microbiome: a brief review. Frontiers in pediatrics, 3, 17.
A large number of microbes are known to colonize the infant’s gut in the first days of life. The initial microbiota establishment represents a crucial stage for gut maturation and metabolic and immunologic programming and has important consequences for short- and long-term health, see Jost, T., Lacroix, C., Braegger, C., & Chassard, C. (2015). Impact of human milk bacteria and oligosaccharides on neonatal gut microbiota establishment and gut health. Nutrition reviews, 73(7), 426-437.
Pigs coexist with a diverse and dense commensal microbiota in their gastrointestinal tract. Most of these microbes are beneficial, providing necessary nutrients or protection against harmful pathogens for the host. The microbial colonization of the porcine intestine begins at birth and follows a rapid succession during the neonatal and weaning period. The intestinal immune system of the newborn piglet is poorly developed at birth and undergoes a rapid period of expansion and specialization that is not achieved before early (commercial-) weaning.
Early weaning of piglets is often accompanied by a severe growth check and diarrhea. This process is multi-factorial and it is clear that post- weaning anorexia and undernutrition are major
etiological factors. Gastrointestinal disturbances include alterations in small intestine architecture and enzyme activities. See Lalles, Jean-Paul, et al. "Nutritional management of gut health in pigs around weaning." Proceedings of the Nutrition Society 66.2 (2007): 260-268. Furthermore, the pig shares many common features of gastrointestinal physiology, microbiology, genetics and diet with humans. Pigs are particularly useful when assessing host microbe interactions because the gut microbiota is substantially more stable over time in both pigs and humans compared with rodent models.
Use of antibiotics for reducing or eradicating gut bacterial pathogens in human or in livestock such as pigs, exerts unwanted side effects, as well as antibiotic resistance on both the treated mammal, and the human consumers.
The animal agriculture sector is a major user of antibiotic drugs for disease treatment, disease control, disease prevention, and“production purposes” (such as growth promotion).
Routine use of antibiotics— in humans or animals— can encourage antimicrobial resistance, which can lead to significant human and animal health risks. Furthermore, in 2013, the U.S. Food and Drug Administration (FDA) issued final guidance on voluntarily phasing out the use of medically important antibiotics (those important for therapeutic use in humans) for livestock production purposes; see Sneeringer, S., MacDonald, J. M., Key, N., McBride, W. D., & Mathews, K. (2017). Economics of antibiotic use in US livestock production.
There is therefore an unmet need to overcome and control microbial diseases, caused by pathogens, without the use of antibiotics.
BRIEF DESCRIPTION OF THE FIGURES
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the principles of the invention.
Fig.l depicting a graphical presentation of a preferred embodiment of the current invention; and
Fig.2 depicting yet another graphical presentation of a preferred embodiment of the current invention.
SUMMARY OF THE INVENTION:
It is thus one object of the present invention to disclose a composition useful for an antibiotic- free composition for control of pathogens in a mammalian subject, characterized by at least three members of a group consisting of steviol glycoside, citric acid monohydrate, monosodium glutamate, glycine, mixtures and derivatives thereof.
It is another object of the present invention to disclose the composition as defined in any of the above, wherein said composition is an oral isotonic composition characterized by no residual chlorine taste.
It is another object of the present invention to disclose the composition as defined in any of the above, wherein said control is reduction in counts of said pathogens in said mammalian subject compared to control mammalian subject.
It is another object of the present invention to disclose the composition as defined in any of the above, wherein said control is elimination of said pathogens in said mammalian subject compared to control mammalian subject.
It is another object of the present invention to disclose the composition as defined in any of the above, wherein said animal is selected from a group consisting at least one of human, cattle, pigs, sheep, goats, horses, mules, asses, buffalo, camels, chickens, turkeys, ducks, geese, guinea fowl, squabs, dogs, or cats of any age.
It is another object of the present invention to disclose the composition as defined in any of the above, wherein said pathogens are selected from a group consisting of Acinetobacter baumannii, Acinetobacter Iwoffii, Acinetobacter spp. (incl. MDR), Actinomycetes, Adenovirus, Aeromonas spp., Alcaligenes faecalis, Alcaligenes spp./Achromobacter spp. Alcaligenes xylosoxidans (incl. ESBL/MRGN), Arbovirus Virucidal, Ascaris lumbricoides, Aspergillus spp. Astrovirus, Bacillus anthracis, Bacillus cereus, Bacillus subtilis, Bacteriodes fragilis, Bartonella quintana, Blastocystis hominis, Bordetella pertussis, Borrelia burgdorferi, Borrelia duttoni, Borrelia recurrentis, Brevundimonas diminuta, Brevundimonas vesicularisBrucella spp., Burkholderia cepacia (incl. MDR), Burkholderia mallei, Burkholderia pseudomalle, Campylobacter jejuni / coliCandida albicans, Candida krusei, Candida parapsilosis, Chikungunya virus (CHIKV), Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Citrobacter spp., Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani,
Coronavirus (incl. SARS- and MERS-CoV), Corynebacterium diphtheria, Corynebacterium pseudotuberculosis, Corynebacterium spp., Corynebacterium ulcerans, Coxiella burnetii, Coxsackievirus, Crimean-Congo haemorrhagic fever virus, Cryptococcus neof ormans, Cryptosporidium hominis, Cryptosporidium parvum e, Cyclospora cayetanensisCytomegalovirus
- CMV, Dengue virus, Dientamoeba fragilis, Ebola virus, Echinococcus spp,. Echovirus, Entamoeba dispar, Entamoeba histolytica, Enterobacter aero genes, Enterobacter cloacae ( incl. ESBL/MRGN), Enterobius vermicularis, Enterococcus faecalis (incl. VRE), Enterococcus faecium (incl. VRE), Enterococcus hirae, Epidermophyton spp. Epstein-Barr virus EBV, Escherichia coli (incl. EHEC, EPEC, ETEC, EIEC, EAEC, ESBL/MRGN, DAEC), Filarial worms, Foot-and-mouth disease virus (FMDV), Francisella tularensis, Giardia lamblia, Haemophilus influenza, Hantavirus, Helicobacter pylori, Helminths (Worms), Hepatitis A virus
- HAV, Hepatitis B virus - HBV, Hepatitis C virus - HCV, Hepatitis D virus, Hepatitis E virus, Herpes simplex virus - HSV, Histoplasma capsulatum, Human enterovirus 71, Human herpesvirus 6 (HHV-6), Human herpesvirus 7 (HHV-7), Human herpesvirus 8 (HHV-8), Human immunodeficiency virus - HIV, Human metapneumovirus, Human papillomavirus, Hymenolepsis nana, Influenza virus, Klebsiella granulomatis, Klebsiella oxytoca (incl. ESBL/MRGN), Klebsiella pneumoniae MDR (incl. ESBL/MRGN), Lassa virus, Leclercia adecarboxylata, Legionella pneumophila, Leishmania spp., Leptospira interrogans, Leuconostoc pseudomesenteroides, Listeria monocytogenes, Marburg virus, Measles virus, Micrococcus luteus, Microsporum spp., Molluscipoxvirus, Morganella spp., Mumps virus, Mycobacterium chimaera Myco, Mycobacterium leprae Myco, Mycobacterium tuberculosis (incl. MDR) Tuberculocidal, Mycoplasma genitalium, Mycoplasma pneumoniae, Neisseria meningitides, Neisseria gonorrhoeae, Norovirus, Opisthorchis viverrini, Orientia tsutsugamushi, Pantoea agglomerans, Paracoccus yeei, Parainfluenza virus, Parvovirus, Pediculus humanus capitis, Pediculus humanus corporis, Plasmodium spp., Pneumocystis jiroveci, Poliovirus, Polyomavirus, Prevotella spp., Propionibacterium species, Proteus mirabilis (incl. ESBL/MRGN), Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa, Pseudomonas spp., Rabies virus, Ralstonia spp., Respiratory syncytial virus - RSV, Rhinovirus, Rickettsia prowazekii, Rickettsia typhi, Roseomonas gilardii, Rotavirus, Rubella virus, Schistosoma mansoni, Salmonella enteritidis, Salmonella paratyphi, Salmonella spp., Salmonella typhimurium, Sarcoptes scabiei (Itch mite), Sapovirus, Serratia marcescens (incl. ESBL/MRGN),
Shigella sonnei, Sphingomonas species, Spirochaetaceae (inc. Brachyspira hyodysenteriae), Staphylococcus aureus (incl. MRSA, VRSA), Staphylococcus capitis, Staphylococcus epidermidis (incl. MRSE), Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus lugdunensis, Staphylococcus pasteuri, Staphylococcus saprophyticus, Stenotrophomonas maltophilia, Streptococcus pneumoniae, Streptococcus pyogenes (incl. PRSP), Streptococcus spp., Strongyloides stercoralis, Taenia solium, TBE virus, Toxoplasma gondii, Treponema pallidum, Trichinella spiralis, Trichomonas vaginalis, Trichophyton spp., Trichosporon spp., Trichuris trichiura, Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Vaccinia virus, Varicella zoster virus, Variola virus, Vibrio cholerae, West Nile virus (WNV), Yellow fever virus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudotuberculosis, Zika virus and any combination thereof.
It is another object of the present invention to disclose the composition as defined in any of the above, wherein said pathogens are gut pathogens.
It is another object of the present invention to disclose the composition as defined in any of the above, wherein said gut pathogen is Escherichia coli.
It is another object of the present invention to disclose the composition as defined in any of the above, wherein said gut pathogen is Brachyspira hyodysenteriae.
It is another object of the present invention to disclose the composition as defined in any of the above, wherein said gut pathogen is Helicobacter pylori.
It is another object of the present invention to disclose the composition as defined in any of the above, wherein said gut pathogen is a member of the Prevotellaceae family.
It is another object of the present invention to disclose the composition as defined in any of the above, wherein said pathogens are pathogenic bacteria, selected from a group consisting of bacteria families Actinomyces, Bacillus, Bartonella, Bordetella, Borrelia, Brucella, Campylobacter, Chlamydia, Clostridium, Corynebacterium, Enterococcus, Escherichia, Escherichia coli, Francisell, Haemophilus, Helicobacter, Helicobacter pylori, Legionella, Leptospira, Listeria, Mycobacterium, Mycoplasma, Neisseria, Prevotellaceae, Pseudomonas, Rickettsia, Salmonella, Shigella, Spirochaetaceae, Staphylococcus, Streptococcus, Treponema, Ureaplasma, Vibrio, Yersinia, and any combination thereof.
It is another object of the present invention to disclose the composition as defined in any of the above wherein said pathogens are gut pathogens selected from the group consisting of bacteria, viruses, fungi, prions, parasites, or protozoan and any combination thereof.
It is another object of the present invention to disclose the composition as defined in any of the above, wherein the composition is in the form selected from the group consisting of a tablet, a capsule, a pill, lyophilized, powder, emulsion, powder, cream, ointment, paste, lotion, gel, liquid, a solution, a patch, suspension, granulated powder, liquid, syrup, cream, foam, capsule, suppository, enema, infusion, enteric-coated pill, enteric-coated capsule, mouth wash, toothpaste, and any combination thereof.
It is another object of the present invention to disclose the composition as defined in any of the above, wherein said composition is configured to be administrable in a manner selected from a group consisting of fast release, slow release, sustained release, controlled release and any combination thereof.
It is thus one object of the present invention to disclose a method of controlling pathogens in a mammalian subject, comprising steps of providing an antibiotic-free composition characterized by at least three members of a group consisting of steviol glycoside, citric acid monohydrate, monosodium glutamate, glycine, mixtures and derivatives thereof.
It is another object of the present invention to disclose the method as defined in any of the above, wherein said composition is an oral isotonic composition characterized by no residual chlorine taste.
It is another object of the present invention to disclose the method as defined in any of the above, wherein said step of controlling is reducing the counts of said pathogens in said mammalian subject, compared to control mammalian subject.
It is another object of the present invention to disclose the method as defined in any of the above, wherein said step of controlling is eliminating said pathogens in said mammalian subject compared to control mammalian subject.
It is another object of the present invention to disclose the method as defined in any of the above, wherein said animal is selected from a group consisting at least one of humans, cattle, pigs, sheep,
goats, horses, mules, asses, buffalo, camels, chickens, turkeys, ducks, geese, guinea fowl, squabs, dogs, or cats of any age.
It is another object of the present invention to disclose the method as defined in any of the above, wherein said pathogens are selected from a group consisting Acinetobacter baumannii, Acinetobacter Iwoffii, Acinetobacter spp. (incl. MDR), Actinomycetes, Adenovirus, Aeromonas spp., Alcaligenes faecalis, Alcaligenes spp./Achromobacter spp. Alcaligenes xylosoxidans (incl. ESBL/MRGN), Arbovirus Virucidal, Ascaris lumbricoides, Aspergillus spp. Astrovirus, Bacillus anthracis, Bacillus cereus, Bacillus subtilis, Bacteriodes fragilis, Bartonella quintana, Blastocystis hominis, Bordetella pertussis, Borrelia burgdorferi, Borrelia duttoni, Borrelia recurrentis, Brevundimonas diminuta, Brevundimonas vesicularisBrucella spp., Burkholderia cepacia (incl. MDR), Burkholderia mallei, Burkholderia pseudomalle, Campylobacter jejuni / coliCandida albicans, Candida krusei, Candida parapsilosis, Chikungunya virus (CHIKV), Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Citrobacter spp., Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Coronavirus (incl. SARS- and MERS-CoV), Corynebacterium diphtheria, Corynebacterium pseudotuberculosis, Corynebacterium spp., Corynebacterium ulcerans, Coxiella burnetii, Coxsackievirus, Crimean-Congo haemorrhagic fever virus, Cryptococcus neof ormans, Cryptosporidium hominis, Cryptosporidium parvum e, Cyclospora cayetanensisCytomegalovirus
- CMV, Dengue virus, Dientamoeba fragilis, Ebola virus, Echinococcus spp,. Echovirus, Entamoeba dispar, Entamoeba histolytica, Enterobacter aero genes, Enterobacter cloacae ( incl. ESBL/MRGN), Enterobius vermicularis, Enterococcus faecalis (incl. VRE), Enterococcus faecium (incl. VRE), Enterococcus hirae, Epidermophyton spp. Epstein-Barr virus EBV, Escherichia coli (incl. EHEC, EPEC, ETEC, EIEC, EAEC, ESBL/MRGN, DAEC), Filarial worms, Foot-and-mouth disease virus (FMDV), Francisella tularensis, Giardia lamblia, Haemophilus influenza, Hantavirus, Helicobacter pylori, Helminths (Worms), Hepatitis A virus
- HAV, Hepatitis B virus - HBV, Hepatitis C virus - HCV, Hepatitis D virus, Hepatitis E virus, Herpes simplex virus - HSV, Histoplasma capsulatum, Human enterovirus 71, Human herpesvirus 6 (HHV-6), Human herpesvirus 7 (HHV-7), Human herpesvirus 8 (HHV-8), Human immunodeficiency virus - HIV, Human metapneumovirus, Human papillomavirus, Hymenolepsis nana, Influenza virus, Klebsiella granulomatis, Klebsiella oxytoca (incl. ESBL/MRGN), Klebsiella pneumoniae MDR (incl. ESBL/MRGN), Lassa virus, Leclercia adecarboxylata,
Legionella pneumophila, Leishmania spp., Leptospira interrogans, Leuconostoc pseudomesenteroides, Listeria monocytogenes, Marburg virus, Measles virus, Micrococcus luteus, Microsporum spp., Molluscipoxvirus, Morganella spp., Mumps virus, Mycobacterium chimaera Myco, Mycobacterium leprae Myco, Mycobacterium tuberculosis (incl. MDR) Tuberculocidal, Mycoplasma genitalium, Mycoplasma pneumoniae, Neisseria meningitides, Neisseria gonorrhoeae, Norovirus, Opisthorchis viverrini, Orientia tsutsugamushi, Pantoea agglomerans, Paracoccus yeei, Parainfluenza virus, Parvovirus, Pediculus humanus capitis, Pediculus humanus corporis, Plasmodium spp., Pneumocystis jiroveci, Poliovirus, Polyomavirus, Prevotella spp., Propionibacterium species, Proteus mirabilis (incl. ESBL/MRGN), Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa, Pseudomonas spp., Rabies virus, Ralstonia spp., Respiratory syncytial virus - RSV, Rhinovirus, Rickettsia prowazekii, Rickettsia typhi, Roseomonas gilardii, Rotavirus, Rubella virus, Schistosoma mansoni, Salmonella enteritidis, Salmonella paratyphi, Salmonella spp., Salmonella typhimurium, Sarcoptes scabiei ( Itch mite), Sapovirus, Serratia marcescens (incl. ESBL/MRGN), Shigella sonnei, Sphingomonas species, Spirochaetaceae (inc. Brachyspira hyodysenteriae ), Staphylococcus aureus (incl. MRSA, VRSA), Staphylococcus capitis, Staphylococcus epidermidis (incl. MRSE), Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus lugdunensis, Staphylococcus pasteuri, Staphylococcus saprophyticus, Stenotrophomonas maltophilia, Streptococcus pneumoniae, Streptococcus pyogenes (incl. PRSP), Streptococcus spp., Strongyloides stercoralis, Taenia solium, TBE virus, Toxoplasma gondii, Treponema pallidum, Trichinella spiralis, Trichomonas vaginalis, Trichophyton spp., Trichosporon spp., Trichuris trichiura, Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Vaccinia virus, Varicella zoster virus, Variola virus, Vibrio cholerae, West Nile virus (WNV), Yellow fever virus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudotuberculosis, Zika virus and any combination thereof.
It is another object of the present invention to disclose the method as defined in any of the above, wherein said pathogens are gut pathogens.
It is another object of the present invention to disclose the method as defined in any of the above, wherein said gut pathogen is Escherichia coli.
It is another object of the present invention to disclose the method as defined in any of the above, wherein said gut pathogen is Brachyspira hyodysenteriae.
It is another object of the present invention to disclose the method as defined in any of the above, wherein said gut pathogen is Helicobacter pylori.
It is another object of the present invention to disclose the method as defined in any of the above, wherein said gut pathogen is a member of the Prevotellaceae family.
It is another object of the present invention to disclose the method as defined in any of the above, wherein said pathogens are pathogenic bacteria, selected from a group consisting of bacteria families Actinomyces, Bacillus, Bartonella, Bordetella, Borrelia, Brucella, Campylobacter, Chlamydia, Clostridium, Corynebacterium, Enterococcus, Escherichia, Escherichia coli, Francis ell, Haemophilus, Helicobacter, Helicobacter pylori, Legionella, Leptospira, Listeria, Mycobacterium, Mycoplasma, Neisseria, Prevotellaceae, Pseudomonas, Rickettsia, Salmonella, Shigella, Spirochaetaceae , Staphylococcus, Streptococcus, Treponema, Ureaplasma, Vibrio, Yersinia and any combination thereof.
It is another object of the present invention to disclose the method as defined in any of the above, wherein said pathogens are gut pathogens selected from the group consisting of bacteria, viruses, fungi, prions, parasites, or protozoan and any combination thereof.
It is another object of the present invention to disclose the method as defined in any of the above, wherein the composition is in the form selected from the group consisting of a tablet, a capsule, a pill, lyophilized, powder, emulsion, powder, cream, ointment, paste, lotion, gel, liquid, a solution, a patch, suspension, granulated powder, liquid, syrup, cream, foam, capsule, suppository, enema, infusion, enteric-coated pill, enteric-coated capsule, mouth wash, toothpaste, and any combination thereof.
It is another object of the present invention to disclose the method as defined in any of the above, wherein the composition is configured to be administrable in a manner selected from a group consisting of fast release, slow release, sustained release, controlled release and any combination thereof.
It is one object of the present invention to disclose a medical device useful for control of pathogens in a mammalian subject; comprising a delivery mechanism, a container in a fluid connection with
said delivery mechanism, wherein said container accommodates an antibiotic-free composition, characterized by at least three members of a group consisting of steviol glycoside, citric acid monohydrate, monosodium glutamate, glycine, mixtures and derivatives thereof.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The following description is provided, alongside all chapters of the present invention, so as to enable any person skilled in the art to make use of the invention and sets forth the best modes contemplated by the inventor of carrying out this invention. Various modifications, however, are adapted to remain apparent to those skilled in the art, since the generic principles of the present invention have been defined specifically to provide compositions and methods for controlling pathogens in mammalian subjects.
The term“livestock” as used herein refers to domesticated animals raised in an agricultural setting to produce labor and commodities such as meat, eggs, milk, fur, leather, and wool. Livestock includes beef and dairy cattle, pigs, sheep, goats, horses, mules, asses, buffalo, alpaca and camels; as well as the raising of birds commercially for meat or eggs, i.e., chickens, turkeys, ducks, geese, guinea fowl, and squabs.
As used herein after, the term pathogen generally refers hereinafter to biological agent or micro organism (microbe) capable of producing disease in the host; i.e. a pathogen or infectious agent is a biological agent that causes disease or illness to its host. Pathogen is a micro-organism that may be inter alia bacteria, viruses, fungi, prions, parasites, or protozoan.
Pathogens comprise the following: Acinetobacter baumannii, Acinetobacter Iwoffii, Acinetobacter spp. (incl. MDR), Actinomycetes, Adenovirus, Aeromonas spp., Alcaligenes faecalis, Alcaligenes spp./Achromobacter spp. Alcaligenes xylosoxidans (incl. ESBL/MRGN), Arbovirus Virucidal, Ascaris lumbricoides, Aspergillus spp. Astrovirus, Bacillus anthracis, Bacillus cereus, Bacillus subtilis, Bacteriodes fragilis, Bartonella quintana, Blastocystis hominis, Bordetella pertussis, Borrelia burgdorferi, Borrelia duttoni, Borrelia recurrentis, Brevundimonas diminuta, Brevundimonas vesicularisBrucella spp., Burkholderia cepacia (incl. MDR), Burkholderia mallei, Burkholderia pseudomalle, Campylobacter jejuni / coliCandida albicans, Candida krusei,
Candida parapsilosis, Chikungunya virus (CHIKV), Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Citrobacter spp., Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Coronavirus (incl. SARS- and MERS-CoV), Corynebacterium diphtheria, Corynebacterium pseudotuberculosis, Corynebacterium spp., Corynebacterium ulcerans, Coxiella burnetii, Coxsackievirus, Crimean-Congo haemorrhagic fever virus, Cryptococcus neoformans, Cryptosporidium hominis, Cryptosporidium parvum e, Cyclospora cayetanensisCytomegalovirus - CMV, Dengue virus, Dientamoeba fragilis, Ebola virus, Echinococcus spp,. Echovirus, Entamoeba dispar, Entamoeba histolytica, Enterobacter aero genes, Enterobacter cloacae (incl. ESBL/MRGN), Enterobius vermicularis, Enterococcus faecalis (incl. VRE), Enterococcus faecium (incl. VRE), Enterococcus hirae, Epidermophyton spp. Epstein-Barr virus EBV, Escherichia coli (incl. EHEC, EPEC, ETEC, EIEC, EAEC, ESBL/MRGN, DAEC), Filarial worms, Foot-and-mouth disease virus (FMDV), Francisella tularensis, Giardia lamblia, Haemophilus influenza, Hantavirus, Helicobacter pylori, Helminths (Worms), Hepatitis A virus - HAV, Hepatitis B virus - HBV, Hepatitis C virus - HCV, Hepatitis D virus, Hepatitis E virus, Herpes simplex virus - HSV, Histoplasma capsulatum, Human enterovirus 71, Human herpesvirus 6 (HHV-6), Human herpesvirus 7 (HHV-7), Human herpesvirus 8 (HHV-8), Human immunodeficiency virus - HIV, Human metapneumovirus, Human papillomavirus, Hymenolepsis nana, Influenza virus, Klebsiella granulomatis, Klebsiella oxytoca (incl. ESBL/MRGN), Klebsiella pneumoniae MDR (incl. ESBL/MRGN), Lassa virus, Leclercia adecarboxylata, Legionella pneumophila, Leishmania spp., Leptospira interrogans, Leuconostoc pseudomesenteroides, Listeria monocytogenes, Marburg virus, Measles virus, Micrococcus luteus, Microsporum spp., Molluscipoxvirus, Morganella spp., Mumps virus, Mycobacterium chimaera Myco, Mycobacterium leprae Myco, Mycobacterium tuberculosis (incl. MDR) Tuberculocidal, Mycoplasma genitalium, Mycoplasma pneumoniae, Neisseria meningitides, Neisseria gonorrhoeae, Norovirus, Opisthorchis viverrini, Orientia tsutsugamushi, Pantoea agglomerans, Paracoccus yeei, Parainfluenza virus, Parvovirus, Pediculus humanus capitis, Pediculus humanus corporis, Plasmodium spp., Pneumocystis jiroveci, Poliovirus, Polyomavirus, Prevotella spp., Propionibacterium species, Proteus mirabilis (incl. ESBL/MRGN), Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa, Pseudomonas spp., Rabies virus, Ralstonia spp., Respiratory syncytial virus - RSV, Rhinovirus, Rickettsia prowazekii, Rickettsia typhi, Roseomonas gilardii, Rotavirus, Rubella virus, Schistosoma mansoni, Salmonella
enteritidis, Salmonella paratyphi, Salmonella spp., Salmonella typhimurium, Sarcoptes scabiei ( Itch mite), Sapovirus, Serratia marcescens (incl. ESBL/MRGN), Shigella sonnei, Sphingomonas species, Spirochaetaceae (inc. Brachyspira hyodysenteriae ), Staphylococcus aureus (incl. MRSA, VRSA), Staphylococcus capitis, Staphylococcus epidermidis (incl. MRSE), Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus lugdunensis, Staphylococcus pasteuri, Staphylococcus saprophyticus, Stenotrophomonas maltophilia, Streptococcus pneumoniae, Streptococcus pyogenes (incl. PRSP), Streptococcus spp., Strongyloides stercoralis, Taenia solium, TBE virus, Toxoplasma gondii, Treponema pallidum, Trichinella spiralis, Trichomonas vaginalis, Trichophyton spp., Trichosporon spp., Trichuris trichiura, Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Vaccinia virus, Varicella zoster virus, Variola virus, Vibrio cholerae, West Nile virus (WNV), Yellow fever virus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudotuberculosis, Zika virus.
As used herein after, the term pathogenic bacteria generally refers hereinafter to bacteria that can cause disease. A pathogenic bacterium comprises the following bacteria families: Actinomyces, Bacillus, Bartonella, Bordetella, Borrelia, Brucella, Campylobacter, Chlamydia, Clostridium, Corynebacterium, Enterococcus, Escherichia, Escherichia coli, Francis ell, Haemophilus, Helicobacter, Legionella, Leptospira, Listeria, Mycobacterium, Mycoplasma, Neisseria, Prevotellaceae, Pseudomonas, Rickettsia, Salmonella, Shigella, Spirochaetaceae, Staphylococcus, Streptococcus, Treponema, Ureaplasma, Vibrio, Yersinia.
As used herein after, the term gut pathogens refers hereinafter to gastrointestinal pathogenic bacteria, viruses, fungi, prions, parasites, or protozoan, comprising inter alia bacteria of the following types: Escherichia Coli, Salmonella, Campylobacter, Virio cholera, Shigella, Clostridium pertingens, Bacillus cereus, and Yersnia entercolitica while pathogen viruses comprise inter alia rotavirus and small round viruses.
The term“steviol” refers hereinafter to steviol glycoside, Rebaudioside A extract.
The current invention discloses compositions and methods for controlling pathogens; eradicating, eliminating or reducing counts of pathogens in mammalian subjects. Specifically, the current invention refers to the enterotrophic effect of an isotonic composition, Px, when administered to piglets during the first week of life and Px-gruel when administered in the immediate pre-and post-
weaning period, resulting in significant reductions in intestinal E. coli load in the Px- administered piglets.
It is in the scope of the invention wherein aforesaid non-genetically-modified compositions, products and formulations comprise or based on commercially available Px (trade mark) by Tonisity International Ltd, namely, a composition, e.g., defined below:
Table 1: Ingredients of Px formulation.
Ingredients (%)
glucose anhydrous 1.5540
monosodium glutamate 0.3900
sodium chloride, vacuum dried 0.2201
citric acid anhydrous 0.1860
potassium chloride 0.1500
glycine 0.1500
hydrolyzed whey protein isolate 0.1500
monosodium dihydrogen phosphate 0.1000
xanthan gum 0.0500
l-glutamic acid 0.0400
stevia (min. 85 % steviol glycoside extract) 0.0100 demineralized water 97.000
The sum of all solutes in the Px solution is 3%. The composition consists of at least two members of a group consisting of steviol glycoside, citric acid monohydrate, monosodium glutamate and glycine, this composition characterized by that that the composition consists of at least three members of a group consisting of steviol glycoside, citric acid monohydrate, monosodium glutamate and glycine. Additionally or alternatively, this composition is characterized by that said composition consisting of steviol glycoside, citric acid monohydrate, monosodium glutamate and glycine.
EXAMPLE 1
Two basic morphometric histopathology studies were done to investigate the effects of Tonisity Px when administered to piglets from days 2 to 8 of age and when given for 3 days before and after weaning. These studies showed a significant increase in villi height in the Px group. The effect related to whether or not Px had been given from days 2 to 8.
Introduction The rapid development of the intestinal environment in the neonatal pig sets the stage for production performance as well as nutrient absorption in the intestine. The aim of this study was to assess the effect of an isotonic protein drink on intestinal morphology and microbial population in the first 30 days of the pig’s life.
Materials and Methods Fifteen (15) gilts (Yorkshire x Landrace x Duroc) and their litters (161 piglets) were enrolled in the study which was performed in a dedicated high-health research facility. Litters were allocated to one of two study groups, control (Group A) or supplementation with an isotonic protein solution (Group B). Group A litters received no supplementation during the suckling or pre-weaning phase, and were given creep feed from weaning up until two days after weaning in addition to having feeder access. From days 2-8 of age, group B litters were given 500 mL of a 3% isotonic protein solution once daily in an open pan. Group B litters also received the 3% solution three and two days before weaning followed by a gruel mixture from one day before weaning up until two days after weaning. Weaning was at 21 days.
Table 2: Treatment Groups
A total of 56 piglets were randomly selected from each litter for euthanasia at 9 and 17 days of age and a further 20 piglets were randomly selected from each treatment group at 30 days of age. (Samples of small intestine and ingesta from each piglet were evaluated for differences in intestinal histomorphometry, thickness of intestinal mucus layer, semi-quantitative aerobic bacterial culture, and rotaviruses PCR at the University of Minnesota Veterinary Diagnostic Laboratory.) Samples taken from the ileal mucosa of each piglet were also submitted for semiquantitative aerobic bacterial culture (E. coli).
Table 3. Test Products
Feeding and Treatment Administration Plan All sows were fed while in the farrowing room according to farm management practices and were fed a standard farm lactation diet. Sows had ad lib access to fresh water through the watering system. Piglets did not have access to creep feed before weaning except as indicated in the feeding schedule. Piglets had access to an automatic drinker while in the farrowing pen.
Test product was given to the litters as follows:
a. Day 2-8, pans of Px was placed in each farrowing pen and filled once daily with 500 mL of solution per day.
b. Three (3) days before weaning, Px litters were given 500 mL of 3% Px solution in an open pan, in the farrowing pen.
c. Two (2) days before weaning, Px litters were given 500 mL of 3% Px solution in an open pan, in the farrowing pen.
d. One day before weaning, Px litters were given 2 lb/litter (~ 65 g/pig) of Px-gruel (made with a 3% solution) in an open pan, in the farrowing pen.
e. On weaning day, all pigs were weighed individually and allotted to pens based on body weight and treatment group. Once in the weaning pens, Px pigs received 15 lb* per 30 pigs of Px-gruel (made with the concentration of Px solution and the creep feed as specified in Table 3) in a separate feeder. The 15 lbs of gruel was split into 2 portions, a.m. (¼ lb per pig) and p.m. (¼ lb per pig). Dry feed and fresh water were made available. Control pigs received no gruel.
f. The Px-gruel administration was continued for the next 3 days after weaning
* 6 lb of dry feed + 1 gallon of Px solution
Table 4. Feeding Schedule for Treatment Groups
Results Days 9 and 17 microbiology and viral PCR showed that Group B pigs had significantly fewer numbers of subjects with E. coli (P = 0.01). Group A control pigs had 14/26 (54%) subjects positive for E. coli, with 4 pigs having positive results for beta-hemolytic E. coli. Group B pigs had 7/30 (23%) subjects positive for E. coli, with 1 pig having positive results for beta-hemolytic E. coli. There was an even distribution of E. coli cases between day 9 (12 cases total, 8 in Group A and 4 in Group B) and day 17 (9 cases total, 6 in Group A and 3 in Group B).
Overall (preweaning and postweaning combined) pigs from Group B tended to have fewer pigs positive for E. coli (10/40, 25%) compared to Control pigs (15/36, 42%) (P = 0.06), representing a 40% reduction from birth until day 30 of age. See Figure 1, where the percentage of positive results for E. coli cultures is graphically represented for Group A (control group) and Group B (Px-administered pigs) on days 9 and 17 of the pigs’ life, as well as the preweaning average.
Conclusion Enterotoxigenic E. coli (ETEC) is an important pathogen in neonatal and post weaning pigs as it can negatively impact production performance. The administration of an isotonic protein drink in the first week of life was associated with significant reductions in intestinal E. coli load in this study.
EXAMPLE 2
Experiment was conducted as described in example 1. In example 2, fecal samples were collected from each pig for pathogen detection and analysis. The analysis included 16S rRNA gene sequencing. 16S rRNA gene sequencing was performed using the MiSeq (Illumina) platform after PCR amplification of the 16S v4 region. Data was normalized to the lowest number of reads per pig (3157), as the rarefaction curves revealed a plateau after this point.
PCR and genetic sequencing were preformed to detect the presence of members of the Prevotellaceae family. Some Prevotella have been previously associated with intestinal disturbances due to weaning stress in pigs and are known intestinal mucus degraders, See Gresse R, Chaucheyras- Durand F, Fleury MA et al. Gut microbiota dysbiosis in postweaning piglets: understanding the keys to health. Trends Microbiol Elsevier Current Trends, 2017;25:851-873, and Arumugam M, Raes J, Pelletier E et al. Enterotypes of the human gut microbiome. Nature Nature Publishing Group, 2011;473: 174-180.
The results indicate that the presence of Prevotellaceae was significantly lower in Group B (Px- administered pigs) compared to Group A (control) at days 9 and 17 (20.5% and 27.6% vs 29.0% and 37.0%, respectively; P < 0.01). These differences represent a 29% reduction at day 9 and a 25% reduction at day 17. No differences were observed at day 30 of life. See Figure 2, where the percentage of positive results for Prevotellaceae cultures is graphically represented for Group A (control group) and Group B (Px-administered pigs) on days 9, 17 and 30 of the pigs’ life.
EXAMPLE 3
Experiment was conducted as described in example 2. PCR and genetic sequencing were preformed to detect the presence of the Spirochaetaceae family which includes the known porcine pathogen Brachyspira hyodysenteriae. This bacterium induces mucohemorrhagic diarrhea in pigs, with mortality and morbidity approaching 30% and 90%, respectively, see Schweer W.P, Gabler N.K, et al. Impact of Brachyspira hyodysenteriae on intestinal amino acid digestibility and endogenous amino acid losses in pigs.Journal of Animal Science, October, 2018;97: 1-12.
The results of the experiment show that Group B (Px-administered pigs) had lower amounts of Spirochaetaceae compared to Group A (control group) at day 9 (0.04% vs 0.15%; P < 0.05).
EXAMPLE 4
Experiment was conducted as described in example 2. PCR and genetic sequencing were preformed to detect the presence of Helicobacter pylori. Previous publications have linked the presence of this bacterium to several types of cancers, including gastric cancer, low-grade mucosa- associated lymphoid tissue (MALT) lymphoma and pancreatic ductal adenocarcinoma, see Mentis A., Papavassiliou A. G., et al. Helicobacter pylori infection and gastric cancer biology: tempering a double-edged sword. Cellular and molecular life science, July 20l9;76 (13): 2477-2486 and Wei M.Y, Yu X. G., et al. The microbiota and microbiome in pancreatic cancer: more influential than expected. Molecular Cancer, 2019;18: 1-15.
The results obtained from this experiment demonstrate that the odds of detecting Helicobacter in Group A (control group) at day 9 were 4.3 times higher than in Group B (Px-administered pigs) (P=0.08).
Claims
1. An antibiotic-free composition for control of pathogens in a mammalian subject, characterized by at least three members of a group consisting of steviol glycoside, citric acid monohydrate, monosodium glutamate, glycine, mixtures and derivatives thereof.
2. The composition of claim 1, wherein said composition is an oral isotonic composition characterized by no residual chlorine taste.
3. The composition of claim 1, wherein said control is reduction in counts of said pathogens in said mammalian subject compared to control mammalian subject.
4. The composition of claim 1, wherein said control is elimination of said pathogens in said mammalian subject compared to control mammalian subject.
5. The composition of claim 4, wherein said animal is selected from a group consisting of at least one of human, cattle, pigs, sheep, goats, horses, mules, asses, buffalo, camels, chickens, turkeys, ducks, geese, guinea fowl, squabs, dogs, or cats of any age.
6. The composition of claim 1 , wherein said pathogens are selected from a group consisting of Acinetobacter baumannii, Acinetobacter Iwoffii, Acinetobacter spp. (incl. MDR), Actinomycetes, Adenovirus, Aeromonas spp., Alcaligenes faecalis, Alcaligenes spp./Achromobacter spp. Alcaligenes xylosoxidans (incl. ESBL/MRGN), Arbovirus Virucidal, Ascaris lumbricoides, Aspergillus spp. Astrovirus, Bacillus anthracis, Bacillus cereus, Bacillus subtilis, Bacteriodes fragilis, Bartonella quintana, Blastocystis hominis, Bordetella pertussis, Borrelia burgdorferi, Borrelia duttoni, Borrelia recurrentis, Brevundimonas diminuta, Brevundimonas vesicularisBrucella spp., Burkholderia cepacia (incl. MDR), Burkholderia mallei, Burkholderia pseudomalle, Campylobacter jejuni / coliCandida albicans, Candida krusei, Candida parapsilosis, Chikungunya virus ( CHIKV), Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Citrobacter spp., Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Coronavirus (incl. SARS- and MERS-CoV), Corynebacterium diphtheria, Corynebacterium pseudotuberculosis, Corynebacterium spp., Corynebacterium ulcerans, Coxiella burnetii, Coxsackievirus, Crimean-Congo haemorrhagic fever virus, Cryptococcus neoformans, Cryptosporidium hominis, Cryptosporidium parvum e, Cyclospora cayetanensisCytomegalovirus - CMV, Dengue virus, Dientamoeba fragilis, Ebola virus, Echinococcus spp,. Echovirus, Entamoeba dispar, Entamoeba histolytica, Enterobacter
aero genes, Enterobacter cloacae (incl. ESBL/MRGN), Enterobius vermicularis, Enterococcus faecalis (incl. VRE), Enterococcus faecium (incl. VRE), Enterococcus hirae, Epidermophyton spp. Epstein-Barr virus EBV, Escherichia coli (incl. EHEC, EPEC, ETEC, EIEC, EAEC, ESBL/MRGN, DAEC), Filarial worms, Foot-and-mouth disease virus (FMDV), Francisella tularensis, Giardia lamblia, Haemophilus influenza, Hantavirus, Helicobacter pylori, Helminths (Worms), Hepatitis A virus - HAV, Hepatitis B virus - HBV, Hepatitis C virus - HCV, Hepatitis D virus, Hepatitis E virus, Herpes simplex virus - HSV, Histoplasma capsulatum, Human enterovirus 71, Human herpesvirus 6 (HHV-6), Human herpesvirus 7 (HHV-7), Human herpesvirus 8 (HHV-8), Human immunodeficiency virus - HIV, Human metapneumovirus, Human papillomavirus, Hymenolepsis nana, Influenza virus, Klebsiella granulomatis, Klebsiella oxytoca (incl. ESBL/MRGN), Klebsiella pneumoniae MDR (incl. ESBL/MRGN), Lassa virus, Leclercia adecarboxylata, Legionella pneumophila, Leishmania spp., Leptospira interrogans, Leuconostoc pseudomesenteroides, Listeria monocytogenes, Marburg virus, Measles virus, Micrococcus luteus, Microsporum spp., Molluscipoxvirus, Morganella spp., Mumps virus, Mycobacterium chimaera Myco, Mycobacterium leprae Myco, Mycobacterium tuberculosis (incl. MDR) Tuberculocidal, Mycoplasma genitalium, Mycoplasma pneumoniae, Neisseria meningitides, Neisseria gonorrhoeae, Norovirus, Opisthorchis viverrini, Orientia tsutsugamushi, Pantoea agglomerans, Paracoccus yeei, Parainfluenza virus, Parvovirus, Pediculus humanus capitis, Pediculus humanus corporis, Plasmodium spp., Pneumocystis jiroveci, Poliovirus, Polyomavirus, Prevotella spp., Propionibacterium species, Proteus mirabilis (incl. ESBL/MRGN), Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa, Pseudomonas spp., Rabies virus, Ralstonia spp., Respiratory syncytial virus - RSV, Rhinovirus, Rickettsia prowazekii, Rickettsia typhi, Roseomonas gilardii, Rotavirus, Rubella virus, Schistosoma mansoni, Salmonella enteritidis, Salmonella paratyphi, Salmonella spp., Salmonella typhimurium, Sarcoptes scabiei (Itch mite), Sapovirus, Serratia marcescens (incl. ESBL/MRGN), Shigella sonnei, Sphingomonas species, Spirochaetaceae (inc. Brachyspira hyodysenteriae ), Staphylococcus aureus (incl. MRSA, VRSA), Staphylococcus capitis, Staphylococcus epidermidis (incl. MRSE), Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus lugdunensis, Staphylococcus pasteuri, Staphylococcus saprophyticus, Stenotrophomonas maltophilia, Streptococcus
pneumoniae, Streptococcus pyogenes (incl. PRSP), Streptococcus spp., Strongyloides stercoralis, Taenia solium, TBE virus, Toxoplasma gondii, Treponema pallidum, Trichinella spiralis, Trichomonas vaginalis, Trichophyton spp., Trichosporon spp., Trichuris trichiura, Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Vaccinia virus, Varicella zoster virus, Variola virus, Vibrio cholerae, West Nile virus (WNV), Yellow fever virus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudotuberculosis, Zika virus and any combination thereof.
7. The composition of claim 1, wherein said pathogens are gut pathogens.
8. The composition of claim7, wherein said gut pathogen is Escherichia coli.
9. The composition of claim7, wherein said gut pathogen is Brachyspira hyodysenteriae.
10. The composition of claim7, wherein said gut pathogen is Helicobacter pylori.
11. The composition of claim7, wherein said gut pathogen is a member of the Prevotellaceae family.
12. The composition of claim 1 wherein said pathogens are pathogenic bacteria, selected from a group consisting of bacteria families Actinomyces, Bacillus, Bartonella, Bordetella, Borrelia, Brucella, Campylobacter, Chlamydia, Clostridium, Corynebacterium, Enterococcus, Escherichia, Escherichia coli, Francisell, Haemophilus, Helicobacter, Helicobacter pylori, Legionella, Leptospira, Listeria, Mycobacterium, Mycoplasma, Neisseria, Prevotellaceae, Pseudomonas, Rickettsia, Salmonella, Shigella, Spirochaetaceae , Staphylococcus, Streptococcus, Treponema, Ureaplasma, Vibrio cholera, Yersinia, and any combination thereof.
13. The composition of claim 1, wherein said pathogens are gut pathogens selected from the group consisting of bacteria, viruses, fungi, prions, parasites, or protozoan and any combination thereof.
14. The composition of claim 1, wherein the composition is in the form selected from the group consisting of a tablet, a capsule, a pill, lyophilized, powder, emulsion, powder, cream, ointment, paste, lotion, gel, liquid, a solution, a patch, suspension, granulated powder, liquid, syrup, cream, foam, capsule, suppository, enema, infusion, enteric-coated pill, enteric- coated capsule, mouth wash, toothpaste and any combination thereof.
15. The composition of claim 1, wherein said composition is configured to be administrable in a manner selected from a group consisting of fast release, slow release, sustained release, controlled release and any combination thereof.
16. A method for controlling pathogens in a mammalian subject, comprising steps of providing an antibiotic-free composition characterized by at least three members of a group consisting of steviol glycoside, citric acid monohydrate, monosodium glutamate, glycine, mixtures and derivatives thereof.
17. The method of claim 16, wherein said composition is an oral isotonic composition characterized by no residual chlorine taste.
18. The method of claim 16, wherein said step of controlling is reducing the counts of said pathogens in said mammalian subject, compared to control mammalian subject.
19. The method of claim 16, wherein said step of controlling is eliminating said pathogens in said mammalian subject compared to control mammalian subject.
20. The method of claim 16, wherein said animal is selected from a group consisting of at least one of humans, cattle, pigs, sheep, goats, horses, mules, asses, buffalo, camels, chickens, turkeys, ducks, geese, guinea fowl, squabs, dogs, or cats of any age.
21. The method of claim 16, wherein said pathogens are selected from a group consisting of Acinetobacter baumannii, Acinetobacter Iwoffii, Acinetobacter spp. (incl. MDR), Actinomycetes, Adenovirus, Aeromonas spp., Alcaligenes faecalis, Alcaligenes spp./Achromobacter spp. Alcaligenes xylosoxidans (incl. ESBL/MRGN), Arbovirus Virucidal, Ascaris lumbricoides, Aspergillus spp. Astrovirus, Bacillus anthracis, Bacillus cereus, Bacillus subtilis, Bacteriodes fragilis, Bartonella quintana, Blastocystis hominis, Bordetella pertussis, Borrelia burgdorferi, Borrelia duttoni, Borrelia recurrentis, Brevundimonas diminuta, Brevundimonas vesicularisBrucella spp., Burkholderia cepacia (incl. MDR), Burkholderia mallei, Burkholderia pseudomalle, Campylobacter jejuni / coliCandida albicans, Candida krusei, Candida parapsilosis, Chikungunya virus ( CHIKV), Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Citrobacter spp., Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Coronavirus (incl. SARS- and MERS-CoV), Corynebacterium diphtheria, Corynebacterium pseudotuberculosis, Corynebacterium spp., Corynebacterium ulcerans, Coxiella burnetii, Coxsackievirus, Crimean-Congo haemorrhagic fever virus, Cryptococcus neoformans,
Cryptosporidium hominis, Cryptosporidium parvum e, Cyclospora cayetanensisCytomegalovirus - CMV, Dengue virus, Dientamoeba fragilis, Ebola virus, Echinococcus spp,. Echovirus, Entamoeba dispar, Entamoeba histolytica, Enterobacter aero genes, Enterobacter cloacae (incl. ESBL/MRGN), Enterobius vermicularis, Enterococcus faecalis (incl. VRE), Enterococcus faecium (incl. VRE), Enterococcus hirae, Epidermophyton spp. Epstein-Barr virus EBV, Escherichia coli (incl. EHEC, EPEC, ETEC, EIEC, EAEC, ESBL/MRGN, DAEC), Filarial worms, Foot-and-mouth disease virus (FMDV), Francisella tularensis, Giardia lamblia, Haemophilus influenza, Hantavirus, Helicobacter pylori, Helminths (Worms), Hepatitis A virus - HAV, Hepatitis B virus - HBV, Hepatitis C virus - HCV, Hepatitis D virus, Hepatitis E virus, Herpes simplex virus - HSV, Histoplasma capsulatum, Human enterovirus 71, Human herpesvirus 6 (HHV-6), Human herpesvirus 7 (HHV-7), Human herpesvirus 8 (HHV-8), Human immunodeficiency virus - HIV, Human metapneumovirus, Human papillomavirus, Hymenolepsis nana, Influenza virus, Klebsiella granulomatis, Klebsiella oxytoca (incl. ESBL/MRGN), Klebsiella pneumoniae MDR (incl. ESBL/MRGN), Lassa virus, Leclercia adecarboxylata, Legionella pneumophila, Leishmania spp., Leptospira interrogans, Leuconostoc pseudomesenteroides, Listeria monocytogenes, Marburg virus, Measles virus, Micrococcus luteus, Microsporum spp., Molluscipoxvirus, Morganella spp., Mumps virus, Mycobacterium chimaera Myco, Mycobacterium leprae Myco, Mycobacterium tuberculosis (incl. MDR) Tuberculocidal, Mycoplasma genitalium, Mycoplasma pneumoniae, Neisseria meningitides, Neisseria gonorrhoeae, Norovirus, Opisthorchis viverrini, Orientia tsutsugamushi, Pantoea agglomerans, Paracoccus yeei, Parainfluenza virus, Parvovirus, Pediculus humanus capitis, Pediculus humanus corporis, Plasmodium spp., Pneumocystis jiroveci, Poliovirus, Polyomavirus, Prevotella spp., Propionibacterium species, Proteus mirabilis (incl. ESBL/MRGN), Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa, Pseudomonas spp., Rabies virus, Ralstonia spp., Respiratory syncytial virus - RSV, Rhinovirus, Rickettsia prowazekii, Rickettsia typhi, Roseomonas gilardii, Rotavirus, Rubella virus, Schistosoma mansoni, Salmonella enteritidis, Salmonella paratyphi, Salmonella spp., Salmonella typhimurium, Sarcoptes scabiei (Itch mite), Sapovirus, Serratia marcescens (incl. ESBL/MRGN), Shigella sonnei, Sphingomonas species, Spirochaetaceae (inc. Brachyspira hyodysenteriae ), Staphylococcus aureus (incl. MRSA, VRSA),
Staphylococcus capitis, Staphylococcus epidermidis (incl. MRSE), Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus lugdunensis, Staphylococcus pasteuri, Staphylococcus saprophyticus, Stenotrophomonas maltophilia, Streptococcus pneumoniae, Streptococcus pyogenes (incl. PRSP), Streptococcus spp., Strongyloides stercoralis, Taenia solium, TBE virus, Toxoplasma gondii, Treponema pallidum, Trichinella spiralis, Trichomonas vaginalis, Trichophyton spp., Trichosporon spp., Trichuris trichiura, Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Vaccinia virus, Varicella zoster virus, Variola virus, Vibrio cholerae, West Nile virus (WNV), Yellow fever virus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudotuberculosis, Zika virus and any combination thereof.
22. The method of claim 16, wherein said pathogens are gut pathogens.
23. The method of claim 22, wherein said gut pathogen is Escherichia coli.
24. The method of claim 22, wherein said gut pathogen is Brachyspira hyodysenteriae.
25. The method of claim 22, wherein said gut pathogen is Helicobacter pylori.
26. The method of claim 22, wherein said gut pathogen is a member of the Prevotellaceae family.
27. The method of claim 16, wherein said pathogens are pathogenic bacteria, selected from a group consisting of bacteria families Actinomyces, Bacillus, Bartonella, Bordetella, Borrelia, Brucella, Campylobacter, Chlamydia, Clostridium, Corynebacterium, Enterococcus, Escherichia, Escherichia coli, Francis ell, Haemophilus, Helicobacter, Helicobacter pylori, Legionella, Leptospira, Listeria, Mycobacterium, Mycoplasma, Neisseria, Prevotellaceae, Pseudomonas, Rickettsia, Salmonella, Shigella, Spirochaetaceae , Staphylococcus, Streptococcus, Treponema, Ureaplasma, Vibrio, Yersinia and any combination thereof.
28. The method of claim 16, wherein said pathogens are gut pathogens selected from the group consisting of bacteria, viruses, fungi, prions, parasites, or protozoan and any combination thereof.
29. The method of claim 16, wherein the composition is in the form selected from the group consisting of a tablet, a capsule, a pill, lyophilized, powder, emulsion, powder, cream, ointment, paste, lotion, gel, liquid, a solution, a patch, suspension, granulated powder, liquid,
syrup, cream, foam, capsule, suppository, enema, infusion, enteric-coated pill, enteric- coated capsule, mouth wash, toothpaste , and any combination thereof.
30. The method of claim 16, wherein the composition is configured to be administrable in a manner selected from a group consisting of fast release, slow release, sustained release, controlled release and any combination thereof.
31. A medical device useful for control of pathogens in a mammalian subject; comprising a delivery mechanism, a container in a fluid connection with said delivery mechanism, wherein said container accommodates an antibiotic-free composition, characterized by at least three members of a group consisting of steviol glycoside, citric acid monohydrate, monosodium glutamate, glycine, mixtures and derivatives thereof.
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EP1629724A1 (en) * | 2004-08-27 | 2006-03-01 | PURAC Biochem BV | The use of glycine and/or a glycine derivative as antibacterial agent in foods and/or drinks |
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US20170339997A1 (en) * | 2014-11-19 | 2017-11-30 | Kalmarna Limited | Oral rehydration composition and methods thereof |
US20180153841A1 (en) * | 2014-11-19 | 2018-06-07 | Kalmarna Limited | Compositions and methods for induction of remission of inflammatory bowel diseases |
US20180214404A1 (en) * | 2014-11-19 | 2018-08-02 | Kalmarna Limited | Oral nourishing composition and methods thereof |
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EP1629724A1 (en) * | 2004-08-27 | 2006-03-01 | PURAC Biochem BV | The use of glycine and/or a glycine derivative as antibacterial agent in foods and/or drinks |
US20170339997A1 (en) * | 2014-11-19 | 2017-11-30 | Kalmarna Limited | Oral rehydration composition and methods thereof |
US20180153841A1 (en) * | 2014-11-19 | 2018-06-07 | Kalmarna Limited | Compositions and methods for induction of remission of inflammatory bowel diseases |
US20180214404A1 (en) * | 2014-11-19 | 2018-08-02 | Kalmarna Limited | Oral nourishing composition and methods thereof |
CN106265810A (en) * | 2016-08-29 | 2017-01-04 | 晨光生物科技集团股份有限公司 | A kind of stevia rebaudiana phenol extract and the application in preparing antibacterial goods thereof |
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