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WO1998006277A1 - Formules nutritionnelles completees en nucleotides, et procedes correspondants - Google Patents

Formules nutritionnelles completees en nucleotides, et procedes correspondants Download PDF

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Publication number
WO1998006277A1
WO1998006277A1 PCT/US1997/014111 US9714111W WO9806277A1 WO 1998006277 A1 WO1998006277 A1 WO 1998006277A1 US 9714111 W US9714111 W US 9714111W WO 9806277 A1 WO9806277 A1 WO 9806277A1
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WO
WIPO (PCT)
Prior art keywords
formula
nucleotides
infant
bioavailable
free
Prior art date
Application number
PCT/US1997/014111
Other languages
English (en)
Inventor
H. Lee Leary
Robert A. Burns
Original Assignee
Bristol-Myers Squibb Company
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 Bristol-Myers Squibb Company filed Critical Bristol-Myers Squibb Company
Priority to AU39769/97A priority Critical patent/AU3976997A/en
Publication of WO1998006277A1 publication Critical patent/WO1998006277A1/fr

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Classifications

    • 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 OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/152—Milk preparations; Milk powder or milk powder preparations containing additives
    • A23C9/1526—Amino acids; Peptides; Protein hydrolysates; Nucleic acids; Derivatives thereof
    • 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
    • A23L33/13—Nucleic acids or derivatives thereof

Definitions

  • the present invention relates to nutritional formulas containing nucleotides and/or nucleosides. Specifically, the present invention relates to milk-based and non-milk-based nutritional formulas which are supplemented with nucleotides and/or nucleosides and to processes for making such formulas. The present invention also relates to a method of reducing the incidence of constipation in infant-formula fed infants and to a method for softening stools of infant-formula fed babies.
  • Nucleotides are low molecular-weight compounds consisting of a nitrogenous base, a sugar moiety and one to three phosphate groups. They are essential in energy metabolism and enzymatic reactions and are the monomeric units of polymeric RNA and DNA. Nucleotides are an integral part of carbohydrate, lipid, protein and nucleic acid metabolism. Nucleosides are similar to nucleotides except that they do not include a phosphate group or groups. As used herein the term "nucleotide equivalents" shall mean either or both nucleotides and nucleosides.
  • Human milk contains a number of nucleotides and nucleosides.
  • a number of studies identified nucleotides and nucleosides present in human milk and their levels. Nucleosides are believed to be present primarily in free bioavailable form. Nucleotides can be present in free bioavailable forms or in bound forms that have to be broken down in order to be metabolized.
  • a number of studies have been carried out to determine nucleotides and nucleosides present in human milk and their levels in human milk. Examples of published results of such studies include the following: Janas, L.M. and Picciano, M.F., (1982), "The Nucleotide Profile of Human Milk," Pediatr. Res., 16:659- 62; Gil, A.
  • Cow's milk and nutritional formulas based on milk or non-milk ingredients generally also contain nucleotides and nucleosides.
  • the types and/or levels of nucleotides and nucleosides present in human milk are different from those present in cow's milk and in nutritional formulas made from animal milk or made from non-milk ingredients.
  • Prior art discloses supplementing cow's milk, milk products and nutritional formulas with various nucleotides to make cow's milk, milk products or nutritional formulas similar to human milk.
  • prior art is in disagreement as to what nucleotides should be added and at what concentrations to make the non-human milk, milk-based or non-milk based formulas similar to human milk.
  • U.S. Pat. No. 3,231,385 discloses that there is a difference between nucleotides and nucleotide levels between human milk and cow's milk. The Ziro et al.
  • nucleotide content of cow's milk or other cow milk products similar to human milk nucleotides which are present in human milk but substantially absent in cow's milk may be added.
  • the Ziro et al. patent discloses that "GMP, UMP, CMP and other nucleotide fractions may be added to cow's milk so as to make their content similar to that of human milk.”
  • the nucleotide fractions can be added "as such” or in the form of an alkali salt. See column 4, lines 17-22.
  • the Ziro patent discloses specific levels of added nucleotides per liter of cow's milk without regard to background levels of these nucleotides.
  • U.S. Pat. No. 5,066,500 discloses adding nucleotides and/or nucleosides to nutritional products and to formulas and processes for their preparation. The purpose of this addition is to provide formulas having enhanced physiological properties and also closely resemble human milk.
  • the '500 patent recognizes that "it would be desirable that infant milk formulas have most of the substances present in human milk so as to produce the same physiological effects as human milk.”
  • Column 2, lines 2-5 Adenosine, guanosine, cytidine, inosine, uridine are the specific nucleosides disclosed in the '500 patent.
  • Mono, di, and/or tri phosphates of these nucleosides or their sugar derivatives are the nucleotides disclosed in the '500 patent.
  • the '500 patent discloses adding at least one of these nucleotides or nucleosides.
  • the '500 patent discloses adding from 1 to 300 mg of the nucleotides and/or nucleosides per 100 g of a diet formulation, preferably about 50 to about 250 mg and optionally 150 mg per 100 g of the formulation.
  • the concentrations of these nucleotides in a liquid formulation from about 20 to about 600 mg per liter of the formulation, preferably about 100 to about 500 mg per liter.
  • the optimum concentration is 300 mg per liter of the formulation.
  • the disclosed amounts of nucleotides added per lOOg of a non-milk infant formula are in the following ranges:
  • concentrations of free bioavailable nucleotides used to supplement infant formulas as disclosed in the Masor et al. patents are higher than the corresponding concentrations found in human milk. Since the roles and functions of nucleotides are not fully understood, these high levels of nucleotides present a risk of adverse effects on the babies fed with the supplemented formulas made in accordance with the Masor et al. patents.
  • Uridine 5' - monophosphate 1.75 mg/100 kcal
  • Adenosine 5' - monophosphate 1.50 mg/100 kcal
  • Guanosine 5' - monophosphate .50 mg/100 kcal
  • nucleotides In addition to adding nucleotides for nutritional purposes, nucleotides have also been added for therapeutic purposes. Therapeutic uses of nucleotides are disclosed in several patents. For example, U.S. Pat. No. 4,544,559 discloses the addition of several specific nucleotides to cow's milk in a specific molar ratio in order to enhance the growth of the bifido bacteria B. bifidum Ti. The '559 patent discloses that all five specified nucleotides needed to be present and in specified molar ratios to achieve the desired results.
  • the five nucleotides include: uridine monophosphate (UMP), guanosine monophosphate (GMP), adenosine monophosphate (AMP), cytidine monophosphate (CMP) and inosine nucleotides (IMP).
  • UMP uridine monophosphate
  • GMP guanosine monophosphate
  • AMP adenosine monophosphate
  • CMP cytidine monophosphate
  • IMP inosine nucleotides
  • the specified ratios for AMP, CMP, GMP, UMP and IMP were 1:1:1:3:0.5, respectively.
  • U.S. Pat. No. 4,994,442 discloses adding of a "therapeutically effective amount" of the ingredients, including nucleotides or nucleosides to a formula.
  • the formula containing nucleotides or nucleosides is intended for patients in need of enhanced immune response of T-cells and for the stimulation or repair and regeneration of intestinal gut cells.
  • milk-based or non-milk- based nutritional formulas are supplemented with free bioavailable nucleotide equivalents so that the resulting levels of free bioavailable nucleotide equivalents in the formulas substantially match the general levels of the corresponding nucleotides present in human milk.
  • the levels of total free bioavailable nucleotides in the nutritional formulas of the present invention are generally in the following approximate ranges:
  • the levels of total free bioavailable nucleotides in the formulas of the present invention are in the following ranges:
  • a dry powder nutritional formula contains the following nucleotides per gram of the powder formula: ( 1 ) from about 0.039 mg to about 0.086 mg UMP; (2) from about 0.016 mg to about 0.047 mg GMP;
  • the nucleotides at levels that match the levels found in human milk are added to a liquid formula after the heat treatment but before homogenization.
  • a method of reducing incidence of constipation in formula fed infants comprises feeding infants the above-described infant formulas with free bioavailable nucleotides at levels substantively matching the levels of free bioavailable nucleotides in human milk.
  • a process for preparing a supplemented infant nutritional formula comprises the steps of measuring the amount, if any, of free bioavailable nucleotides present in the formula and adding free bioavailable nucleotides to the formula such that nucleotides present in the resulting supplemented formula substantially match the mean value of free bioavailable nucleotides present in human milk (the mean value of human milk as defined in J.L. Leach, et al. (1995) "Total Potentially Available Nucleosides in Human Milk by Stage of Lactation," Am. J. Clin. Nutri., 61:1224-30, hereby incorporated by reference).
  • nucleotides present in human milk can best be achieved in nutritional formulas by matching the total levels of free bioavailable nucleotides in the formula to those of the corresponding free nucleotides present in human milk. Since standard ingredients of nutritional formulas generally contain small amounts of free bioavailable nucleotides (background levels), the amounts of free bioavailable nucleotides that are added must be adjusted to account for these background levels.
  • the levels of free bioavailable nucleotide equivalents present in the nutritional formulas should be generally in the following ranges:
  • nucleotides are in the following ranges:
  • the term “free bioavailable nucleotide equivalent” means and encompasses any and all of monomeric nucleotides, nucleosides and their salts. This term does not encompass polymeric forms of nucleotides or nucleosides and specifically it does not encompass nucleotide adducts or nucleotides present in DNA or RNA.
  • non-human protein means animal proteins (such as, cow-, bovine- or sheep-milk proteins) or vegetable proteins (such as, soy rice or the like proteins) or proteins derived from animal or vegetable proteins.
  • CMP CMP, AMP, GMP and UMP are not limited to monophosphate forms of nucleotides. Instead, these terms include the corresponding nucleosides and related free bioavailable nucleotide equivalents, including diphosphates (CDP, ADP, GDP, UDP) and triphosphates (CTP, ATP, GTP, UTP).
  • CDP diphosphates
  • ADP ADP
  • GDP GDP
  • UDP triphosphates
  • CTP triphosphates
  • ATP ATP
  • GTP GTP
  • UTP triphosphates
  • CMP encompasses not only cytidine monophosphate but all monomeric cytidine nucleotides, nucleosides and salts of these nucleotides and nucleosides.
  • the nutritional formula supplemented with the nucleotides in accordance with the present invention be nutritionally complete.
  • the term "nutritionally complete” means that the composition contains adequate nutrients to sustain healthy human life for extended periods.
  • the nutritionally complete formula that can be supplemented with nucleotides in accordance with the present invention contains ingredients which are designed to meet the nutritional needs of the human infant namely, a protein, carbohydrate and lipid source and other nutrients such as vitamins and minerals.
  • the amount of protein per 100 Cal. of total formula is typically about 1.8 g to about 4.5 g; the amount of lipid source per 100 Cal. of total formula is typically about 3.3 g to about 6 g; and the amount of carbohydrate source per 100 Cal.
  • the protein source can be non-fat milk solids, a combination of non-fat milk solids and whey protein, a hydrolysate of non-fat milk and/or why solids, soy protein isolates, or hydrolyzed soy protein isolates.
  • the infant formula can be casein predominant or whey predominant.
  • the carbohydrate source in the infant formula (other than starch) can be any carbohydrate known in the art to be suitable for use in infant formulas. Typical carbohydrate sources include sucrose, fructose, glucose, maltodextrin, lactose, corn syrup, corn syrup solids, and the like.
  • the formula may optionally contain starch, such as, nutritionally complete waxy corn, waxy rice and potato starch preferably in an amount effective to ameloriate regurgitation. Such an amount is typically about 1.8 to about 5 g of starch per 100 Cal. of formula; preferred is about 2 to about 4.7 g of starch per 100 Cal. of formula; more preferred is about 2 to about 3 g of starch per 100 Calories of formula.
  • the lipid source in the infant formula can be any lipid or fat known in the art to be suitable for use in infant formulas.
  • Typical lipid sources include milk fat, safflower oil, egg yolk lipid, olive oil, coconut oil, palm oil, palm kernel oil, soybean oil, sunflower oil, fish oil and fractions derived thereof such as palm olein, medium chain triglycerides (MCT), and esters of fatty acids wherein the fatty acids are, for example, arachidonic acid, linoleic acid, palmitic acid, stearic acid, docosahexaenoic acid, eicosapentaenoic acid, linolenic acid, oleic acid, lauric acid, capric acid, caprylic acid, caproic acid, and the like.
  • MCT medium chain triglycerides
  • High oleic forms of various oils are also contemplated to be useful herein such as high oleic sunflower oil and high oleic safflower oil.
  • Medium chain triglycerides contain higher concentrations of caprylic and capric acid than typically found in conventional oils, e.g. approximately three-fourths of the total fatty acid content is caprylic acid and one-fourth is capric acid.
  • Nutritionally complete formulas contain all vitamins and minerals understood to be essential in the daily diet and these should be present in nutritionally significant amounts. Those skilled in the art appreciate that minimum requirements have been established for certain vitamins and minerals that are known to be necessary for normal physiological function. Those skilled in the art also understand that appropriate additional amounts (overages) of vitamin and mineral ingredients need to be provided to compensate for some loss during processing and storage of such compositions. To select a specific vitamin or mineral compound to be used in the infant formula of the invention requires consideration of that compound's chemical nature regarding compatibility with the particular processing conditions used and shelf storage.
  • Examples of minerals, vitamins and other nutrients optionally present in the composition of the invention include vitamin A, vitamin B 6 vitamin Bj 2 , vitamin E, vitamin K, vitamin C, folic acid, thiamine, inositol, riboflavin, niacin, biotin, pantothenic acid, choline, calcium phosphorus, iodine, iron, magnesium, copper, zinc, manganese, chloride, potassium, sodium, selenium, chromium, molybdenum, taurine, and L-carnitine. Minerals are usually added in salt form. In addition to compatibility and stability considerations, the presence and amounts of specific minerals and other vitamins will vary somewhat depending on the intended infant population.
  • the complete nutritional formulas also typically contain emulsifiers and stabilizers such as soy lecithin, carrageenan, and the like. They may also optionally contain other substances which may have a beneficial effect such as lactoferrin, immunoglobulins, and the like.
  • the complete nutritional formula can be in concentrate liquid form, liquid ready to consume form, or powder form. Of course, if in powder form, the formula is diluted to normal strength with water to be in a form ready to consume.
  • the osmolality of the liquid nutritionally complete formula (when ready to consume) is typically about 100 to 500 mOsm/kg H 2 O more typically about 200 to 400 mOsm/kg H 2 O.
  • the nucleotides in the formula for purposes of matching the nucleotides in the formula to the levels of the corresponding nucleotides present in human milk, only free bioavailable nucleotides are considered.
  • the reason for following this approach is that it is believed that potentially available nucleotides which are present, for example, in polymeric forms in human milk are not broken down in time to be utilized. Additionally, it is important to match the total levels of each free bioavailable nucleotide to the level of the corresponding free bioavailable nucleotide present in human milk.
  • the total levels of free nucleotides in the formula include the levels in the standard ingredients, such as, in the whey protein and the added nucleotides that are not destroyed during processing.
  • the nucleotides are preferably added in form of monophosphates or salts of monophosphates.
  • the added AMP nucleotide is intended to match the combined levels of free AMP, ADP, ATP and adenosine detected in human milk.
  • the added GMP nucleotide is intended to match the combined levels of free GMP, GDP, GTP and guanosine detected in human milk.
  • the added CMP nucleotide is intended to match the combined levels of free CMP, CDP, CTP and cytidine.
  • the added UMP nucleotide is intended to match the combined levels of UMP, UDP, UTP and uridine. Because recent studies indicate that free inosine nucleotides are not present in human milk, they are not currently added to the formulas.
  • the amount of nucleotide equivalents that are added during the process should be adjusted to maintain the free nucleotide equivalent levels at the preferred target concentrations such as: AMP 5.0 mg/L ; GMP 4.0 mg L; CMP 11.0 mg/L and UMP 6.0 mg L.
  • the total amounts of the added and the background nucleotide equivalents is generally slightly higher than the preferred target concentrations to account for losses of nucleotide equivalents during processing.
  • infant formulas typically include (without limitation) proteins in form of reduced minerals whey, casein, non-fat milk, vegetable proteins and casein hydrolysates. They also include vegetable oil (preferably in form of palm olein, soy, coconut and high oleic sunflower), carbohydrates (preferably in form of lactose, glucose, sucrose, starch or hydrolyzed starch), vitamins, minerals, taurine, carnitine, inositol and choline.
  • a typical liquid infant formula has 20 Cal per fluid ounce of the formula.
  • processes for making nutritional formulas includes a step of heating the formula to temperature of about 200°F to 300°F, preferably 260°F to 280°F. Such processes also generally include a step of homogenizing the ingredients in the formula.
  • the nucleotides are preferably added to a liquid formula after the heat treatment, but before the homogenization of the formula.
  • the nucleotides are preferably added in a pre-mixed liquid ("a premix").
  • a premix generally includes the amounts of nucleotides needed to produce the required concentrations in the final product and a carrier liquid.
  • the premix can also include trace elements, such as zinc, copper and manganese.
  • a common concern in monitoring the well-being of infants is whether the infant is constipated. Frequency in stools is desirable without reaching the point of diarrhea.
  • the invention therefore, provides a method of reducing incidence of constipation in infants fed the infant formulas described herein.
  • a method of softening stools of infant formula fed infants wherein said infants are fed a nutritional formula as described herein.
  • nucleotides are dry blended with the remaining ingredients at the end of the manufacturing process.
  • EXAMPLE 2 The background levels of nucleotides in a standard commercial nutritional milk- based liquid formula were determined and the formula was then supplemented with the following nucleotides (in mg/L of the formula):
  • nucleotides in a standard commercial nutritional milk- based formula were measured and the formula was then supplemented with the following amounts of nucleotides to produce the following levels in the supplemented formula (in mg/L of formula):
  • a standard 20 cal/fl. oz. milk-based liquid formula was supplemented with 0.696 kg of nucleotide premix per 10,000 liters of the liquid formula.
  • the premix contained the following amounts of nucleotides per gram of premix:
  • a standard milk-based nutritional liquid concentrate was supplemented with 1.391 kg of the premix having the composition specified in Example 4 per 10,000 L of the concentrate.
  • a standard milk-based liquid concentrate with Iron was supplemented with 1.391 kg of the premix specified in Example 4 per 10,000 L of the concentrate.
  • a standard commercial nutritional powder formula with iron was supplemented with a nucleotide premix by dry blending the nucleotides with other ingredients of the powder formula as the last step of the process.
  • the premix contained the following amounts of nucleotides per 100 kg of the supplemented formula: Cytidine Monophosphate 6.510 g

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Abstract

Des formules nutritionnelles lactées ou non lactées sont complétées en nucléotides de façon que les niveaux totaux des nucléotides biodisponibles libres contenus dans les formules complétées soient conformes aux niveaux correspondants des nucléotides biodisponibles libres présents dans le lait maternel humain. Les quantités des nucléotides sont ajustées en fonction des niveaux de base de nucléotides biodisponibles libres présent dans d'autres ingrédients des formules. Les nucléotides sont ajoutés après traitement thermique, mais avant homogénéisation. L'adjonction de nucléotides à de tels niveaux dans les formules infantiles pour atteindre sensiblement les niveaux de nucléotides biodisponibles libres correspondant aux niveaux trouvés dans le lait maternel humain permet d'obtenir, chez le bébé nourri avec la formule, une consistance des matières fécales proche de celle des bébés nourri au lait maternel humain.
PCT/US1997/014111 1996-08-13 1997-08-12 Formules nutritionnelles completees en nucleotides, et procedes correspondants WO1998006277A1 (fr)

Priority Applications (1)

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AU39769/97A AU3976997A (en) 1996-08-13 1997-08-12 Nutritional formulas supplemented with nucleotides, and processes thereof

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US2387696P 1996-08-13 1996-08-13
US60/023,876 1996-08-13

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004032651A1 (fr) * 2002-10-10 2004-04-22 Wyeth Preparation pour nourrisson contenant des nucleotides
WO2005018343A1 (fr) * 2003-08-18 2005-03-03 Abbott Laboratories Preparations nutritionnelles pour nourrissons a base de soja, enrichies en calcium
US8168611B1 (en) 2011-09-29 2012-05-01 Chemo S.A. France Compositions, kits and methods for nutrition supplementation
US8183227B1 (en) 2011-07-07 2012-05-22 Chemo S. A. France Compositions, kits and methods for nutrition supplementation
WO2015084160A1 (fr) * 2013-12-06 2015-06-11 N.V. Nutricia Dérivé de pyrimidine et source d'acides gras destinés à être utilisés dans le traitement de la constipation
WO2016053096A1 (fr) * 2014-09-30 2016-04-07 N.V. Nutricia Nouvelle composition destinée à la prévention de troubles gastro-intestinaux
EP2356914B1 (fr) 2005-12-23 2020-12-09 N.V. Nutricia Composition pour améliorer la composition de la membrane et le fonctionnement de cellules

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WO1995018618A2 (fr) * 1994-01-10 1995-07-13 Abbott Lab Formule enterale a base de ribonucleotides
US5488039A (en) * 1994-01-10 1996-01-30 Abbott Laboratories Method for the production of an enteral formula containing ribo-nucleotides

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WO1995018618A2 (fr) * 1994-01-10 1995-07-13 Abbott Lab Formule enterale a base de ribonucleotides
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LEACH J.L.; ET AL: "TOTAL POTENTIALLY AVAILABLE NUCLEOSIDES OF HUMAN MILK BY STAGE OF LACTATION", AMERICAN JOURNAL OF CLINICAL NUTRITION, vol. 61, no. 6, 1995, USA, pages 1224 - 1230, XP002048455 *

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004032651A1 (fr) * 2002-10-10 2004-04-22 Wyeth Preparation pour nourrisson contenant des nucleotides
CN1310601C (zh) * 2002-10-10 2007-04-18 惠氏公司 含核苷酸的婴儿配方
EP2050345A1 (fr) * 2002-10-10 2009-04-22 Wyeth Formule infantile contenant des nucléotides
SG165994A1 (en) * 2002-10-10 2010-11-29 Wyeth Corp Infant formula containing nucleotides
AU2010203123B2 (en) * 2002-10-10 2012-03-29 Nestec S.A. Infant formula containing nucleotides
WO2005018343A1 (fr) * 2003-08-18 2005-03-03 Abbott Laboratories Preparations nutritionnelles pour nourrissons a base de soja, enrichies en calcium
EP2356914B1 (fr) 2005-12-23 2020-12-09 N.V. Nutricia Composition pour améliorer la composition de la membrane et le fonctionnement de cellules
US8183227B1 (en) 2011-07-07 2012-05-22 Chemo S. A. France Compositions, kits and methods for nutrition supplementation
US8545896B2 (en) 2011-09-29 2013-10-01 Chemo S. A. France Compositions, kits and methods for nutrition supplementation
US8168611B1 (en) 2011-09-29 2012-05-01 Chemo S.A. France Compositions, kits and methods for nutrition supplementation
WO2015084160A1 (fr) * 2013-12-06 2015-06-11 N.V. Nutricia Dérivé de pyrimidine et source d'acides gras destinés à être utilisés dans le traitement de la constipation
WO2015084158A1 (fr) * 2013-12-06 2015-06-11 N.V. Nutricia Dérivé de pyrimidine et source d'acides gras destinés à être utilisés pour traiter la constipation
CN105979939A (zh) * 2013-12-06 2016-09-28 N.V.努特里西阿公司 用于治疗便秘的嘧啶衍生物和脂肪酸源
US10517885B2 (en) 2013-12-06 2019-12-31 N. V. Nutricia Pyrimidine derivative and a fatty acid source for use in the treatment of constipation
WO2016053096A1 (fr) * 2014-09-30 2016-04-07 N.V. Nutricia Nouvelle composition destinée à la prévention de troubles gastro-intestinaux
WO2016053085A1 (fr) * 2014-09-30 2016-04-07 N.V. Nutricia Composition comprenant une source d'uridine et des fibres produisant du butyrate, utilisable en vue de la prévention de troubles gastro-intestinaux
EP3939580A1 (fr) * 2014-09-30 2022-01-19 N.V. Nutricia Nouvelle composition pour la prévention de troubles gastro-intestinaux

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