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WO2016043583A1 - Réduction de l'anxiété chez la progéniture - Google Patents

Réduction de l'anxiété chez la progéniture Download PDF

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Publication number
WO2016043583A1
WO2016043583A1 PCT/NL2015/050636 NL2015050636W WO2016043583A1 WO 2016043583 A1 WO2016043583 A1 WO 2016043583A1 NL 2015050636 W NL2015050636 W NL 2015050636W WO 2016043583 A1 WO2016043583 A1 WO 2016043583A1
Authority
WO
WIPO (PCT)
Prior art keywords
oligosaccharides
oligosaccharide
digestible oligosaccharide
use according
fructo
Prior art date
Application number
PCT/NL2015/050636
Other languages
English (en)
Inventor
Johan Garssen
Aletta Desiree Kraneveld
Original Assignee
N.V. Nutricia
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by N.V. Nutricia filed Critical N.V. Nutricia
Priority to CN201580061897.1A priority Critical patent/CN107106582A/zh
Priority to EP15794326.7A priority patent/EP3193886A1/fr
Publication of WO2016043583A1 publication Critical patent/WO2016043583A1/fr

Links

Classifications

    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
    • A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
    • 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
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • 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
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/733—Fructosans, e.g. inulin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin

Definitions

  • the present invention relates to the field of nutrition or nutritional supplements for lactating women, in particular nutrition that provides health benefits for the progeny of the pregnant women after birth thereof.
  • the start of life is a stressful phase and from the moment it is born, an infant can be exposed to all kinds of factors that can influence the infant's state of mind. It can be expected that the mother of a newborn does anything to positively influence the way her baby feels.
  • the present inventors In searching for factors that could be of help as a nutritional support for a breastfeeding or lactating mother to positively influence her baby, the present inventors now surprisingly found that by administering prebiotics to lactating mothers, their progeny displayed reduced anxiety. This was evidenced in a mouse model by a decrease in the vocalisations that were emitted by the progeny in the early stage of life when they were only breast-fed by their mothers, and where the mothers received a diet that was supplemented with prebiotics compared to progeny that were breast-fed by mothers that received a control diet without the prebiotics.
  • the present invention relates to a method for reducing anxiety in a breast-fed infant by administering a non-digestible oligosaccharide to the breastfeeding mother of the infant.
  • the method for reducing anxiety is a non-medical method.
  • the invention can also be worded as the use of a non-digestible oligosaccharide in the manufacture of a composition for reducing anxiety in a breast-fed infant wherein the composition comprising a non-digestible oligosaccharide is administered to the breastfeeding mother of the infant.
  • the invention can also be worded as a non-digestible oligosaccharide for use in reducing anxiety in a breast-fed infant by administering non-digestible oligosaccharide to the breastfeeding mother of the infant.
  • the present method or use involves the administration of a non-digestible oligosaccharide.
  • the non-digestible oligosaccharide in the method or use according to the present invention is preferably (i) not or only partially digested in the intestine by the action of acids or digestive enzymes present in the human upper digestive tract (small intestine and stomach) and (ii) fermented by the human intestinal flora, preferably fermentable into organic acids, preferably into lactic acid, butyrate, propionate and/or acetate.
  • sucrose, lactose, maltose and the maltodextrins are considered digestible.
  • the non-digestible oligosaccharide has a DP from 2 to 250, more preferably from 2 to 60.
  • the non- digestible oligosaccharide is at least one, preferably at least two selected from the group consisting of fructo-oligosaccharides, galacto-oligosaccharides, gluco- oligosaccharides, arabino-oligosaccharides, mannan-oligosaccharides, xylo- oligosaccharides, fuco-oligosaccharides, arabinogalacto-oligosaccharides, glucomanno- oligosaccharides, galactomanno-oligosaccharides sialic acid comprising oligosaccharides and uronic acid oligosaccharides.
  • the present composition comprises fructo-oligosaccharides, galacto-oligosaccharides and/or galacturonic acid oligosaccharides, more preferably galacto-oligosaccharides, most preferably beta- galacto-oligosaccharides.
  • the group of fructo-oligosaccharides includes inulin
  • the group of galacto-oligosaccharides includes transgalacto- oligosaccharides or beta- galacto-oligosaccharides
  • the group of gluco-oligosaccharides includes gentio-, nigero- and cyclodextrin-oligosaccharides and polydextrose
  • the group of arabinogalacto- oligosaccharides includes gum acacia
  • the group of galactomanno-oligosaccharides includes partially hydrolysed guar gum.
  • the non-digestible oligosaccharide comprises galacto-oligosaccharide.
  • the galacto-oligosaccharide is preferably selected from the group consisting of beta- galacto-oligosaccharides, lacto-N-tetraose (LNT), lacto-N-neotetraose (neo-LNT), fucosyl-lactose, fucosylated LNT and fucosylated neo-LNT.
  • the non-digestible oligosaccharide comprises beta-galacto- oligosaccharides.
  • Beta-galacto-oligosaccharides as used in the present invention refers to oligosaccharides composed of over 50%, preferably over 65% galactose units based on monomeric subunits, with a degree of polymerization (DP) of 2 to 20, in which at least 50%, more preferably at least 75%, even more preferably at least 90%, of the galactose units are linked together via a beta-glycosidic linkage, preferably a beta- 1,4 glycosidic linkage.
  • the average DP is preferably of 3 to 6.
  • a glucose unit may be present at the reducing end of the chain of galactose units.
  • Beta-galacto- oligosaccharides are sometimes also referred to as transgalacto-oligosacchariodes (TOS).
  • TOS transgalacto-oligosacchariodes
  • a suitable source of beta-galacto-ologosaccharides is Vivinal®GOS (commercially available from Domo Ingredients, Netherlands).
  • Other suitable sources are Oligomate® (Yakult), Cupoligo®, (Nissin) and Bimuno® (Classado).
  • the non-digestible oligosaccharide comprises fructo- oligosaccharide.
  • Fructo-oligosaccharide as used in the present invention refers to oligosaccharides composed of over 50%, preferably over 65 % fructose units based on monomeric subunits, in which at least 50%, more preferably at least 75%, even more preferably at least 90%, of the fructose units are linked together via a beta-glycosidic linkage, preferably a beta-2, 1 glycosidic linkage.
  • a glucose unit may be present at the reducing end of the chain of fructose units.
  • the fructo-oligosaccharide has a DP or average DP of 2 to 250, more preferably 2 to 100, even more preferably 10 to 60.
  • Fructo-oligosaccaride comprises levan, hydrolysed levan, inulin, hydrolysed inulin, and synthesised fructo-oligosaccharides.
  • the non-digestible oligosaccharide comprises short chain fructo-oligosaccharides with an average degree of polymerization (DP) of 3 to 6, more preferably hydrolysed inulin or synthetic fructo- oligosaccharide.
  • the non-digestible oligosaccharide comprises long chain fructo-oligosaccharides with an average DP above 20, such as Orafti HP® (Beneo, Belgium).
  • the composition comprises both short chain and long chain fructo-oligosaccharides.
  • Fructo-oligosaccharide suitable for use in the compositions is also readily commercially available, e.g. Orafti Synergy 1 ® (Beneo, Belgium).
  • the non-digestible oligosaccharide used according to the present invention preferably comprises uronic acid oligosaccharides, more preferably galacturonic acid oligosaccharides.
  • galacturonic acid oligosaccharide refers to an oligosaccharide wherein at least 50% of the monosaccharide units present in the oligosaccharide is galacturonic acid.
  • the galacturonic acid oligosaccharides used in the invention are preferably prepared from degradation of pectin, pectate, and/or polygalacturonic acid.
  • the degraded pectin is prepared by hydrolysis and/or beta-elimination of fruit and/or vegetable pectins, more preferably apple, citrus and/or sugar beet pectin, even more preferably apple, citrus and/or sugar beet pectin degraded by at least one lyase.
  • At least one of the terminal galacturonic acid units of the galacturonic acid oligosaccharide has a double bond.
  • the double bond effectively protects against attachment of pathogenic bacteria to intestinal epithelial cells.
  • one of the terminal galacturonic acid units comprises a C4-C5 double bond.
  • the galacturonic acid oligosaccharide can be derivatised.
  • the galacturonic acid oligosaccharide may be methoxylated and/or amidated.
  • the galacturonic acid oligosaccharides are characterised by a degree of methoxylation above 20%, preferably above 50% even more preferably above 70%.
  • the non-digestible oligosaccharide in the method or use according to the present invention comprises at least beta-galacto-oligosaccharides.
  • the non-digestible oligosaccharide in the method or use according to the present invention comprises at least short chain fructo-oligosaccharides and/or long chain fructo-oligosaccharides, preferably long chain fructo-oligosaccharides.
  • the non-digestible oligosaccharide in the method or use according to the present invention comprises at least uronic acid oligosaccharides.
  • the non-digestible oligosaccharide in the method or use according to the present invention comprises at least beta-galacto-oligosaccharides and at least short chain fructo-oligosaccharides or long chain fructo-oligosaccharides or both. In one embodiment the non-digestible oligosaccharide in the method or use according to the present invention comprises at least beta-galacto-oligosaccharides and at least uronic acid oligosaccharides.
  • the non-digestible oligosaccharide in the method or use according to the present invention comprises at least short chain fructo- oligosaccharides and uronic acid oligosaccharides or long chain fructo-oligosaccharides and uronic acid oligosaccharides. In one embodiment the non-digestible oligosaccharide in the method or use according to the present invention comprises at least beta-galacto-oligosaccharides and short chain fructo-oligosaccharides and uronic acid oligosaccharides or at least beta-galacto-oligosaccharides and long chain fructo- oligosaccharides and uronic acid oligosaccharides.
  • the non-digestible oligosaccharide in the method or use according to the present invention comprises a mixture of inulin and fructo- oligosaccharides.
  • the non-digestible oligosaccharide in the method or use according to the present invention comprises a mixture of galacto- oligosaccharides and fructo-oligosaccharides selected from the group consisting of short chain fructo-oligosaccharides and inulin, more preferably inulin.
  • the non-digestible oligosaccharide in the method or use according to the present invention comprises galacto-oligosaccharides with a DP of 2-10 and fructo-oligosaccharides with a DP of 2- 60.
  • the non-digestible oligosaccharide comprises beta-galacto- oligosaccharide, fructo-oligosaccharide and a pectin degradation product.
  • the weight ratio beta-galacto-oligosaccharide : fructo-oligosaccharide : pectin degradation product is preferably (20 to 2) : 1 : (1 to 20), more preferably (12 to 7) : 1 : (1 to 3).
  • the non-digestible oligosaccharide is administered to the lactating mother in a serving comprising from 0.05 to 50 grams non-digestible oligosaccharide, preferably from 0.1 to 25 grams, preferably from 0.5 to 15 grams, preferably from 1 to 10 grams, preferably from 1 to 5 grams.
  • the present method or use preferably comprises the administration of a serving comprising from 0.05 to 50 grams galacto-oligosaccharide plus fructo-oligosaccharide , preferably from 0.1 to 25 grams, preferably from 0.5 to 15 grams, preferably from 1 to 10 grams, preferably from 1 to 5 grams galacto- oligosaccharide plus fructo-oligosaccharide.
  • the present method or use preferably comprises the administration of a serving comprising from 0.05 to 50 grams galacto- oligosaccharide, preferably from 0.1 to 25 grams, preferably from 0.5 to 15 grams, preferably from 1 to 10 grams, preferably from 1 to 5 grams galacto-oligosaccharide.
  • the present method or use preferably comprises the administration of 0.05 to 50 grams non-digestible saccharide per day, preferably from 0.1 to 25 grams, preferably from 0.5 to 15 grams, preferably from 1 to 10 grams, preferably from 1 to 5 grams per day.
  • the present method or use preferably comprises the administration of 0.05 to 50 grams galacto-oligosaccharide plus fructo-oligosaccharide per day, preferably from 0.1 to 25 grams, preferably from 0.5 to 15 grams, preferably from 1 to 10 grams, preferably from 1 to 5 grams galacto-oligosaccharide plus fructo-oligosaccharide per day.
  • the present method or use preferably comprises the administration of 0.05 to 50 grams galacto- oligosaccharide per day, preferably from 0.1 to 25 grams, preferably from 0.5 to 15 grams, preferably from 1 to 10 gram, preferably from 1 to 5 grams galacto- oligosaccharide per day.
  • a breastfeeding mother includes a woman who taps breast milk and feeds the tapped breast milk via a bottle to the infant.
  • non-digestible oligosaccharide is administered to the breastfeeding mother of the infant.
  • non-digestible oligosaccharide is administered to the breastfeeding mother from the day the infant is born.
  • administration of non-digestible oligosaccharide to the breastfeeding mother is continued until the day the mother stops breastfeeding completely.
  • the present method or use is of benefit for healthy term born infants.
  • the present method or use is of benefit for infants that are prone to develop anxiety.
  • the non-digestible oligosaccharide may be administered to the lactating women in the form of a bar, a capsule, a tablet, a liquid, or a powder.
  • a powder can be mixed with any type of food or beverage prior to intake thereof.
  • non-digestible oligosaccharide is in the form of a nutritional supplement for the lactating women.
  • the non-digestible oligosaccharide is a powder, packed in sachet comprising 1 to 10 g, more preferably 1.5 to 7 g, most preferably 2 to 5 g non-digestible oligosaccharide.
  • the non-digestible oligosaccharide is administered to a lactating woman in an amount from 0.5 to 50 g per day, preferably from 0.1 to 25 g per day, preferably from 0.5 to 15 g per day, preferably from 1 to 10 g per day, preferably from 1 to 5 g per day, preferably from 3 to 25 g per day, preferably from 6 to 12 g per day.
  • this daily dose is administered in one portion per day.
  • this daily dose is divided over 2 or 3 or 4 portions, which are consumed 2, 3 or 4 times per day, respectively.
  • anxiety is reduced in an infant that receives breast milk from a mother that has ingested non-digestible oligosaccharide.
  • Balb/cByJ mice (Charles River Laboratories, Maastricht, The Netherlands) were housed solitary in plastic cages containing standard chip bedding and free access to food and water. Balb/c mice are known as anti-social mice that display increased anxiety-like behavior compared to other murine models.
  • a 12h light dark cycle was followed (7 AM - 7 PM).
  • the day of birth of the pups is postnatal day 0 (P0).
  • P0 postnatal day 0
  • Ultrasonic distress vocalization of male offspring was measured on P10 to determine anxiety-like behavior.
  • the aluminum bottom of the cylinder was connected to a Julabo F12-ED heating circulator (Sigma-Aldrich; Zwijndrecht, The Netherlands) to maintain the temperature at 19 °C.
  • a pup was separated from the dam and its littermates and placed in the cylinder for three minutes, during which the number of calls, average time of calls and average wavelength of calls were measured. Dam and littermates were housed in the same room during this test.
  • Table 1 Pups lactated by a dam fed with scGOS/lcFOS diet show a reduction in ultrasonic vocalizations
  • Control diet AIN93G

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Nutrition Science (AREA)
  • Mycology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

L'anxiété est réduite chez un nourrisson qui reçoit du lait maternel d'une mère ayant ingéré un oligosaccharide non digestible.
PCT/NL2015/050636 2014-09-15 2015-09-15 Réduction de l'anxiété chez la progéniture WO2016043583A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN201580061897.1A CN107106582A (zh) 2014-09-15 2015-09-15 降低后代焦虑
EP15794326.7A EP3193886A1 (fr) 2014-09-15 2015-09-15 Réduction de l'anxiété chez la progéniture

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP14184828.3 2014-09-15
EP14184828 2014-09-15

Publications (1)

Publication Number Publication Date
WO2016043583A1 true WO2016043583A1 (fr) 2016-03-24

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Application Number Title Priority Date Filing Date
PCT/NL2015/050636 WO2016043583A1 (fr) 2014-09-15 2015-09-15 Réduction de l'anxiété chez la progéniture

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EP (1) EP3193886A1 (fr)
CN (1) CN107106582A (fr)
WO (1) WO2016043583A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021105964A1 (fr) * 2019-11-29 2021-06-03 Glycom A/S Mélange de hmos pour améliorer le microbiote de femmes enceintes

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2127661A1 (fr) * 2008-05-27 2009-12-02 Nestec S.A. Probiotiques pour l'amélioration du microbiote intestinal
US20090305996A1 (en) * 2006-03-10 2009-12-10 N.V. Nutricia Use of non-digestable sacharides for giving an infant the best start after birth
WO2013117235A1 (fr) * 2012-02-10 2013-08-15 N.V. Nutricia Supplément pour mères visant à renforcer le système immunitaire d'un nourrisson
WO2013126015A1 (fr) * 2012-02-23 2013-08-29 N. V. Nutricia Composition comprenant des oligosaccharides non digestibles
WO2014070016A2 (fr) * 2012-11-02 2014-05-08 N.V. Nutricia Combinaison symbiotique pour l'amélioration du cerveau

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090305996A1 (en) * 2006-03-10 2009-12-10 N.V. Nutricia Use of non-digestable sacharides for giving an infant the best start after birth
EP2127661A1 (fr) * 2008-05-27 2009-12-02 Nestec S.A. Probiotiques pour l'amélioration du microbiote intestinal
WO2013117235A1 (fr) * 2012-02-10 2013-08-15 N.V. Nutricia Supplément pour mères visant à renforcer le système immunitaire d'un nourrisson
WO2013126015A1 (fr) * 2012-02-23 2013-08-29 N. V. Nutricia Composition comprenant des oligosaccharides non digestibles
WO2014070016A2 (fr) * 2012-11-02 2014-05-08 N.V. Nutricia Combinaison symbiotique pour l'amélioration du cerveau

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
P. BERCIK ET AL: "Microbes and the gut-brain axis", NEUROGASTROENTEROLOGY & MOTILITY, vol. 24, no. 5, 8 May 2012 (2012-05-08), pages 405 - 413, XP055149320, ISSN: 1350-1925, DOI: 10.1111/j.1365-2982.2012.01906.x *
SAVINO F ET AL: "Reduction of crying episodes owing to infantile colic: a randomized controlled study on the efficacy of a new infant formula", vol. 60, no. 11, 1 November 2006 (2006-11-01), pages 1304 - 1310, XP002729499, ISSN: 0954-3007, Retrieved from the Internet <URL:http://www.nature.com/ejcn/journal/v60/n11/pdf/1602457a.pdf> [retrieved on 20140908] *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021105964A1 (fr) * 2019-11-29 2021-06-03 Glycom A/S Mélange de hmos pour améliorer le microbiote de femmes enceintes

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CN107106582A (zh) 2017-08-29
EP3193886A1 (fr) 2017-07-26

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