SG11201703298SA - Activated bifidobacteria and methods of use thereof - Google Patents
Activated bifidobacteria and methods of use thereofInfo
- Publication number
- SG11201703298SA SG11201703298SA SG11201703298SA SG11201703298SA SG11201703298SA SG 11201703298S A SG11201703298S A SG 11201703298SA SG 11201703298S A SG11201703298S A SG 11201703298SA SG 11201703298S A SG11201703298S A SG 11201703298SA SG 11201703298S A SG11201703298S A SG 11201703298SA
- Authority
- SG
- Singapore
- Prior art keywords
- methods
- activated bifidobacteria
- bifidobacteria
- activated
- Prior art date
Links
- 241000186000 Bifidobacterium Species 0.000 title 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
- A61K35/745—Bifidobacteria
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C9/00—Milk preparations; Milk powder or milk powder preparations
- A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/30—Foods or foodstuffs containing additives; Preparation or treatment thereof containing carbohydrate syrups; containing sugars; containing sugar alcohols, e.g. xylitol; containing starch hydrolysates, e.g. dextrin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
-
- 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
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/04—Preserving or maintaining viable microorganisms
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/51—Bifidobacterium
- A23V2400/529—Infantis
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201462068553P | 2014-10-24 | 2014-10-24 | |
US201562133243P | 2015-03-13 | 2015-03-13 | |
PCT/US2015/057226 WO2016065324A1 (en) | 2014-10-24 | 2015-10-23 | Activated bifidobacteria and methods of use thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
SG11201703298SA true SG11201703298SA (en) | 2017-05-30 |
Family
ID=55761664
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SG10202002593SA SG10202002593SA (en) | 2014-10-24 | 2015-10-23 | Activated bifidobacteria and methods of use thereof |
SG11201703298SA SG11201703298SA (en) | 2014-10-24 | 2015-10-23 | Activated bifidobacteria and methods of use thereof |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SG10202002593SA SG10202002593SA (en) | 2014-10-24 | 2015-10-23 | Activated bifidobacteria and methods of use thereof |
Country Status (10)
Country | Link |
---|---|
US (2) | US10716816B2 (en) |
EP (1) | EP3209308B1 (en) |
CN (2) | CN114376234A (en) |
AU (2) | AU2015335601A1 (en) |
BR (1) | BR112017008284A8 (en) |
CA (1) | CA2965663C (en) |
DK (1) | DK3209308T3 (en) |
MX (1) | MX2017005260A (en) |
SG (2) | SG10202002593SA (en) |
WO (1) | WO2016065324A1 (en) |
Families Citing this family (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB201112091D0 (en) | 2011-07-14 | 2011-08-31 | Gt Biolog Ltd | Bacterial strains isolated from pigs |
GB201117313D0 (en) | 2011-10-07 | 2011-11-16 | Gt Biolog Ltd | Bacterium for use in medicine |
GB201306536D0 (en) | 2013-04-10 | 2013-05-22 | Gt Biolog Ltd | Polypeptide and immune modulation |
CN114376234A (en) | 2014-10-24 | 2022-04-22 | 进化生物系统股份有限公司 | Activated bifidobacteria and methods of use thereof |
CN113730442A (en) | 2014-10-31 | 2021-12-03 | 潘德勒姆治疗公司 | Methods and compositions relating to microbial treatment and diagnosis of disorders |
EP3395351A1 (en) | 2014-12-23 | 2018-10-31 | 4D Pharma Research Limited | Immune modulation |
ME03077B (en) | 2014-12-23 | 2019-01-20 | 4D Pharma Res Ltd | Pirin polypeptide and immune modulation |
EP3264922A1 (en) * | 2015-03-05 | 2018-01-10 | Nestec S.A. | Compositions for use in improving stool consistency or frequency in infants or young children |
WO2016149149A1 (en) * | 2015-03-13 | 2016-09-22 | Evolve Biosystems Inc. | Compositions that metabolize or sequester free sugar monomers and uses thereof |
MA41010B1 (en) | 2015-06-15 | 2020-01-31 | 4D Pharma Res Ltd | Compositions comprising bacterial strains |
MD3240554T2 (en) | 2015-06-15 | 2020-01-31 | 4D Pharma Res Ltd | Blautia stercosis and wexlerae for use in treating inflammatory and autoimmune diseases |
MX2017016529A (en) | 2015-06-15 | 2018-03-12 | 4D Pharma Res Ltd | Compositions comprising bacterial strains. |
DK3206700T3 (en) | 2015-06-15 | 2019-08-05 | 4D Pharma Res Ltd | COMPOSITIONS COMPREHENSIVE BAKERY STUES |
MA41060B1 (en) | 2015-06-15 | 2019-11-29 | 4D Pharma Res Ltd | Compositions comprising bacterial strains |
GB201520497D0 (en) | 2015-11-20 | 2016-01-06 | 4D Pharma Res Ltd | Compositions comprising bacterial strains |
PE20181335A1 (en) | 2015-11-20 | 2018-08-21 | 4D Pharma Res Ltd | COMPOSITIONS INCLUDING BACTERIAL STRAINS |
GB201520638D0 (en) | 2015-11-23 | 2016-01-06 | 4D Pharma Res Ltd | Compositions comprising bacterial strains |
GB201520631D0 (en) | 2015-11-23 | 2016-01-06 | 4D Pharma Res Ltd | Compositions comprising bacterial strains |
CN108883139B (en) | 2016-03-04 | 2022-04-26 | 4D制药有限公司 | Compositions comprising bacterial strains |
GB201612191D0 (en) | 2016-07-13 | 2016-08-24 | 4D Pharma Plc | Compositions comprising bacterial strains |
CN109414464A (en) * | 2016-03-11 | 2019-03-01 | 进化生物系统股份有限公司 | For improving the of short duration symbiotic microorganism of intestinal health |
US11318175B2 (en) * | 2016-07-01 | 2022-05-03 | Evolve Biosystems, Inc. | Method for facilitating maturation of the mammalian immune system |
TWI802545B (en) | 2016-07-13 | 2023-05-21 | 英商4D製藥有限公司 | Compositions comprising bacterial strains |
GB201621123D0 (en) | 2016-12-12 | 2017-01-25 | 4D Pharma Plc | Compositions comprising bacterial strains |
RS61872B1 (en) | 2017-05-22 | 2021-06-30 | 4D Pharma Res Ltd | Compositions comprising bacterial strains |
JP6978514B2 (en) | 2017-05-24 | 2021-12-08 | フォーディー ファーマ リサーチ リミテッド4D Pharma Research Limited | Composition containing bacterial strain |
MA49373B1 (en) | 2017-06-14 | 2021-02-26 | 4D Pharma Res Ltd | Compositions comprising bacterial strains |
WO2018229216A1 (en) | 2017-06-14 | 2018-12-20 | 4D Pharma Research Limited | Compositions comprising a bacterial strain of the genus megasphera and uses thereof |
CN107365705B (en) * | 2017-07-14 | 2021-01-12 | 江苏微康生物科技有限公司 | Freeze-drying protective agent for oil-soluble probiotic freeze-dried powder and application thereof |
CA3073838A1 (en) | 2017-08-30 | 2019-03-07 | Pendulum Therapeutics, Inc. | Methods and compositions for treatment of microbiome-associated disorders |
WO2019055718A1 (en) * | 2017-09-13 | 2019-03-21 | Evolve Biosystems, Inc. | Metabolomic revision of mammalian infants |
WO2019143871A1 (en) | 2018-01-17 | 2019-07-25 | Evolve Biosystems, Inc. | Activation of conditionally-expressed oligosaccharide pathways during fermentation of probiotic strains |
CN113164532A (en) * | 2018-05-30 | 2021-07-23 | 进化生物系统股份有限公司 | H5 functional Bifidobacterium longum subspecies infantis compositions and methods of use |
CN113163836A (en) * | 2018-06-01 | 2021-07-23 | 进化生物系统股份有限公司 | Compositions and methods for promoting host defense and stimulating, expanding and/or resetting T cell banks |
WO2019246316A1 (en) * | 2018-06-19 | 2019-12-26 | Evolve Biosystems, Inc. | Novel oligosaccharides for use in prebiotic applications |
BR112022018578A2 (en) * | 2020-03-20 | 2022-11-08 | Glycom As | METHODS FOR DELIVERING A SOLID HMO PRODUCT AND SOLID HMO PRODUCTS OBTAINED THEREBY |
CN111826324A (en) * | 2020-08-05 | 2020-10-27 | 厦门惠盈动物科技有限公司 | Preparation method of lactobacillus rhamnosus powder |
CN114568520A (en) * | 2020-11-30 | 2022-06-03 | 内蒙古伊利实业集团股份有限公司 | Infant formula powder containing bifidobacterium longum subspecies infantis and application thereof |
CN114568516A (en) * | 2020-11-30 | 2022-06-03 | 内蒙古伊利实业集团股份有限公司 | Composition containing bifidobacterium longum subsp. infantis and breast milk oligosaccharide and application thereof |
EP4258901A1 (en) | 2020-12-11 | 2023-10-18 | DSM IP Assets B.V. | Improved prebiotic formulations |
IT202100024911A1 (en) * | 2021-09-29 | 2023-03-29 | Univ Degli Studi Di Napoli Federico Ii Dipartimento Di Fisica Ettore Pancini | PREBIOTIC BASED ON DELACTOSED "SCOTTA" FOR THE PREVENTION AND MANAGEMENT OF INTESTINAL DYSIBIOSIS |
Family Cites Families (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5716615A (en) | 1992-02-10 | 1998-02-10 | Renata Maria Anna Cavaliere Vesely | Dietary and pharmaceutical compositions containing lyophilized lactic bacteria, their preparation and use |
RU2180915C1 (en) | 2001-04-28 | 2002-03-27 | Московский научно-исследовательский институт эпидемиологии и микробиологии им. Г.Н. Габричевского | Consortium of bifidobacteria and lactobacilli used for preparing bacterial preparations, ferments for fermented-milk foodstuffs, fermented and nonfermented foodstuffs, biologically active supplements designated for correction of microflora in children in age below 3 years |
RU2543662C2 (en) * | 2003-10-24 | 2015-03-10 | Н.В. Нютрисиа | Synbiotic composition for children for prevention and treatment of diaper skin rash |
US20070082087A1 (en) * | 2005-10-06 | 2007-04-12 | Schweitzer Biotech Company Ltd. | Fermented milk products containing bifidobacterium longum and isomalto oligosaccharide and the process for producing the same |
EP1776877A1 (en) | 2005-10-21 | 2007-04-25 | N.V. Nutricia | Method for stimulating the intestinal flora |
WO2007140622A1 (en) | 2006-06-09 | 2007-12-13 | Nutravital Inc. | Dairy-derived probiotic compositions and uses thereof |
EP2069520A4 (en) * | 2006-09-15 | 2010-05-05 | Univ California | Bifidobacterial gene sequences and their use |
US8197872B2 (en) | 2007-05-17 | 2012-06-12 | The Regents Of The University Of California | Human milk oligosaccharides to promote growth of beneficial gut bacteria |
WO2008153377A1 (en) * | 2007-06-15 | 2008-12-18 | N.V. Nutricia | Nutrition with non-viable bifidobacterium and non-digestible oligosaccharide |
EP2072052A1 (en) * | 2007-12-17 | 2009-06-24 | Nestec S.A. | Prevention of opportunistic infections in immune-compromised subjects |
UA32462U (en) | 2008-02-14 | 2008-05-12 | Харьковский Национальный Медицинский Университет | Method for evaluation of effectiveness of correction of distortions of intestines microbiotsenosis in children of early age with atopic dermatitis |
CA2658440C (en) * | 2008-04-04 | 2016-08-23 | Kraft Foods Global Brands Llc | Dairy composition with probiotics and anti-microbial system |
EP2143341A1 (en) * | 2008-07-08 | 2010-01-13 | Nestec S.A. | Nutritional Composition Containing Oligosaccharide Mixture |
US20110064707A1 (en) * | 2008-05-27 | 2011-03-17 | Nestec S.A. | Probiotics to improve gut microbiota |
CN102984955B (en) | 2008-11-11 | 2015-01-07 | 营养健康有限公司 | Bifidobacterium longum |
JP2012510476A (en) | 2008-12-02 | 2012-05-10 | プロラクタ バイオサイエンス,インコーポレイテッド | Human milk permeation composition and methods of making and using |
US9649380B2 (en) | 2009-01-12 | 2017-05-16 | Pfizer Italia S.R.L. | Compositions comprising probiotic and prebiotic components and mineral salts, with lactoferrin |
US8198872B2 (en) | 2009-03-10 | 2012-06-12 | Honeywell International, Inc. | Starter-generator with improved excitation |
US7888062B1 (en) * | 2010-02-01 | 2011-02-15 | Microbios, Inc. | Process and composition for the manufacture of a microbial-based product |
EP2536736B1 (en) | 2010-02-19 | 2017-08-16 | Glycom A/S | Production of 6'-o-sialyllactose and intermediates |
ES2680920T3 (en) | 2010-07-12 | 2018-09-11 | The Regents Of The University Of California | Bovine milk oligosaccharides |
EP2465507A1 (en) * | 2010-11-23 | 2012-06-20 | Nestec S.A. | Oligosaccharide composition for treating skin diseases |
EP2454948A1 (en) * | 2010-11-23 | 2012-05-23 | Nestec S.A. | Oligosaccharide mixture and food product comprising this mixture, especially infant formula |
EP2658402A1 (en) * | 2010-12-31 | 2013-11-06 | Abbott Laboratories | Synbiotic combination of probiotic and human milk oligosaccharides to promote growth of beneficial microbiota |
CN104126749A (en) * | 2011-02-10 | 2014-11-05 | 雀巢产品技术援助有限公司 | Modulation of growth of bifidobacteria using a combination of oligosaccharides found in human milk |
US9579353B2 (en) | 2011-06-10 | 2017-02-28 | Prothera, Inc. | Pharmaceutical compositions containing pediococcus and methods for reducing the symptoms of gastroenterological syndromes |
WO2013123223A1 (en) * | 2012-02-14 | 2013-08-22 | The Regents Of The University Of California | Enzymes and methods for cleaving n-glycans from glycoproteins |
CN114376234A (en) | 2014-10-24 | 2022-04-22 | 进化生物系统股份有限公司 | Activated bifidobacteria and methods of use thereof |
EP3229595B1 (en) | 2014-12-12 | 2021-02-03 | The Regents of the University of California | Reduction of milk glycans and their degradation products in the neonate gut |
-
2015
- 2015-10-23 CN CN202111546347.2A patent/CN114376234A/en active Pending
- 2015-10-23 SG SG10202002593SA patent/SG10202002593SA/en unknown
- 2015-10-23 CA CA2965663A patent/CA2965663C/en active Active
- 2015-10-23 CN CN201580071135.XA patent/CN107249611A/en active Pending
- 2015-10-23 DK DK15853612.8T patent/DK3209308T3/en active
- 2015-10-23 SG SG11201703298SA patent/SG11201703298SA/en unknown
- 2015-10-23 US US15/521,502 patent/US10716816B2/en active Active
- 2015-10-23 BR BR112017008284A patent/BR112017008284A8/en not_active Application Discontinuation
- 2015-10-23 WO PCT/US2015/057226 patent/WO2016065324A1/en active Application Filing
- 2015-10-23 AU AU2015335601A patent/AU2015335601A1/en not_active Abandoned
- 2015-10-23 MX MX2017005260A patent/MX2017005260A/en unknown
- 2015-10-23 EP EP15853612.8A patent/EP3209308B1/en active Active
-
2020
- 2020-06-08 US US16/895,641 patent/US20200397837A1/en active Pending
-
2021
- 2021-07-09 AU AU2021204822A patent/AU2021204822A1/en active Pending
Also Published As
Publication number | Publication date |
---|---|
US10716816B2 (en) | 2020-07-21 |
SG10202002593SA (en) | 2020-05-28 |
CN107249611A (en) | 2017-10-13 |
WO2016065324A1 (en) | 2016-04-28 |
MX2017005260A (en) | 2018-01-30 |
BR112017008284A2 (en) | 2017-12-19 |
US20200397837A1 (en) | 2020-12-24 |
EP3209308A4 (en) | 2018-06-27 |
CA2965663C (en) | 2023-04-04 |
EP3209308B1 (en) | 2022-08-03 |
BR112017008284A8 (en) | 2023-04-11 |
CN114376234A (en) | 2022-04-22 |
AU2015335601A1 (en) | 2017-06-01 |
EP3209308A1 (en) | 2017-08-30 |
CA2965663A1 (en) | 2016-04-28 |
US20170304375A1 (en) | 2017-10-26 |
DK3209308T3 (en) | 2022-10-03 |
AU2021204822A1 (en) | 2021-08-05 |
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