Composition containing 2'-fucosyl galactose and method for producing same

Abstract

A method for producing a composition containing 2'-fucosyllactose and 2'-fucosyl galactose by heating a composition, which comprises 2'-fucosyllactose and which is a liquid composition containing water and exhibiting a pH of 5.5-10.0 or a solid composition forming an aqueous solution exhibiting a pH of 5.5-10.0 when dissolved in water, to produce 2'-fucosyl galactose in the composition.

Description

Composition containing 2'-fucosylgalactose and method for producing the same

[0001] The present disclosure relates to compositions comprising 2'-fucosylgalactose and methods for producing the same.

[0002] It has been reported that 2'-fucosylgalactose (2-O-α-L-fucopyranosyl-D-galactose, CAS: 24656-24-4) (hereinafter also referred to as "FucGal" or "fucosylgalactose") has the effect of promoting the proliferation of nerve cells and may therefore be used as a therapeutic agent for neurological diseases such as Alzheimer's disease and Parkinson's disease (Patent Document 1).

[0003] It has been reported that FucGal is produced by reacting 2'-fucosyllactose (2'-O-fucosyllactose, CAS: 41263-94-9) (hereinafter also referred to as "2'FL") with an alkaline solution (pH approximately 11.2) (Non-Patent Document 1), and that it is produced in small amounts by heating a solution containing 2'FL at a pH of less than 5 (Non-Patent Document 2).

[0004] International Publication No. 2019 / 098706

[0005] Richard Kuhn et al., “2-α-L-Fucopyranosyl-D-Galaktose Und 2-α-L-Fucopyranosyl-D-Talose Zur Einwirkung von Alkali auf Oligosaccharide” Justus Liebigs Annalen der Chemie 611 (1), 242-249, 1958GRAS 815 2'-fucosyllactose and difucosyllactose(https: / / www.fda.gov / media / 134910 / download)

[0006] The present disclosure relates to a novel method for easily producing a composition containing 2'-fucosylgalactose, and to a composition that can be easily produced by the method.

[0007] The present disclosure includes the following. [1] A liquid composition containing water and exhibiting a pH of 5.5 to 10.0, or a solid composition that forms an aqueous solution exhibiting a pH of 5.5 to 10.0 when dissolved in water, comprising 2'-fucosyllactose and 2'-fucosylgalactose. [2] The composition according to [1], wherein the concentration of the 2'-fucosylgalactose is 0.01 mg / ml or more based on the volume of the composition. [3] The composition according to [1] or [2], wherein the concentration of the 2'-fucosyllactose is 0.1 mg / ml or more based on the volume of the composition. [4] The composition according to any of [1] to [3], wherein the concentration of 2'-fucosylgalactose is 0.5% or more relative to the concentration of 2'-fucosyllactose. [5] The composition according to any of [1] to [4], wherein the composition further comprises a compound containing a phosphorus atom, and the phosphorus concentration in the composition is 0.05 mg / ml or more based on the volume of the composition. [6] The composition according to any one of [1] to [5], further comprising at least one compound selected from the group consisting of citric acid, citrate salts, acetic acid, acetate salts, phosphoric acid, and phosphate salts. [7] The composition according to any one of [1] to [6], which is a beverage. [8] The composition according to [7], wherein the beverage is a milk beverage or a lactic acid bacteria beverage. [9] The composition according to any one of [1] to [6], which is an infant food or a breast milk fortifier.

[10] A method for producing a composition containing 2'-fucosyllactose and 2'-fucosylgalactose, the method comprising heating a liquid composition containing water and having a pH of 5.5 to 10.0, or a solid composition which, when dissolved in water, forms an aqueous solution having a pH of 5.5 to 10.0, the composition containing 2'-fucosyllactose, to produce 2'-fucosylgalactose in the composition.

[11] The method according to

[10] , wherein the composition is heated so that the concentration (mg / ml) of 2'-fucosylgalactose in the composition after heating is 1% or more of the concentration (mg / ml) of 2'-fucosyllactose in the composition before heating.

[12] The method according to

[10] or

[11] , wherein the composition is heated at 60°C or higher for 10 minutes or more to generate 2'-fucosylgalactose in the composition.

[13] The method according to any one of

[10] to

[12] , wherein the concentration of 2'-fucosyllactose in the composition before heating is 0.1 mg / ml or more.

[14] The method according to any one of

[10] to

[13] , wherein the composition further comprises a compound containing a phosphorus atom, and the phosphorus concentration in the composition before heating is 0.05 mg / ml or more.

[15] A method for increasing the concentration of 2'-fucosylgalactose in a composition containing 2'-fucosyllactose, comprising heating a liquid composition containing water and having a pH of 5.5 to 10.0, or a solid composition that forms an aqueous solution having a pH of 5.5 to 10.0 when dissolved in water, and comprising 2'-fucosyllactose.

[16] The method according to

[15] , wherein the composition is heated so that the concentration of 2'-fucosylgalactose (mg / ml) in the composition after heating is 1% or more of the concentration of 2'-fucosyllactose (mg / ml) in the composition before heating.

[17] The method according to

[15] or

[16] , wherein the composition is heated at 60°C or higher for 10 minutes or more.

[18] The method according to any one of

[15] to

[17] , wherein the concentration of 2'-fucosyllactose in the composition before heating is 0.1 mg / ml or more.

[19] The method according to any one of

[15] to

[18] , wherein the composition further contains a compound containing a phosphorus atom, and the phosphorus concentration in the composition before heating is 0.05 mg / ml or more.

[0008] The present invention also includes the following: [2-1] A method for preventing or treating Alzheimer's disease and / or Parkinson's disease, comprising administering the composition according to any one of [1] to [9] to a subject in need thereof. [2-2] Use of the composition according to any one of [1] to [9] for producing a prophylactic or therapeutic agent for Alzheimer's disease and / or Parkinson's disease. [2-3] The composition according to any one of [1] to [6] for use in the prevention or treatment of Alzheimer's disease and / or Parkinson's disease. [2-4] A method for preventing or treating inflammatory bowel disease, hyperimmune disorders, and / or infectious diseases, comprising administering the composition according to any one of [1] to [9] to a subject in need thereof. [2-5] Use of the composition according to any one of [1] to [9] for producing a prophylactic or therapeutic agent for inflammatory bowel disease, hyperimmune disorders, and / or infectious diseases. [2-6] The composition according to any one of [1] to [9] for use in the prevention or treatment of inflammatory bowel disease, hyperimmune disorders, and / or infectious diseases.

[0009] A novel method for easily producing a composition containing 2'-fucosylgalactose, and a composition that can be easily produced by this method, can be provided.

[0010] The present invention is not limited to the following examples.

[0011] The composition of the present disclosure comprises 2'-fucosyllactose (2'FL) and 2'-fucosylgalactose (FucGal). Examples of such compositions include a liquid composition that further contains water and exhibits a pH of 5.5 to 10.0, or a solid composition that forms an aqueous solution exhibiting a pH of 5.5 to 10.0 when dissolved in water. A liquid composition refers to a composition that is liquid under an environment of 25°C and 1 atmosphere. A solid composition refers to a composition that is solid under an environment of 25°C and 1 atmosphere. The liquid composition of the present disclosure may contain water, and may also contain a solvent other than water. The liquid composition of the present disclosure may also contain a solute other than 2'FL and FucGal. The liquid composition of the present disclosure may also be a colloidal solution. The solid composition of the present disclosure includes compositions in the state of a solid, semi-solid, or viscoelastic material.

[0012] When the composition of the present disclosure is a liquid composition, the liquid composition may have a pH of 5.5 to 10.0 at 25°C and 1 atmospheric pressure, and the pH may be 5.5 to 9.0, preferably 5.3 to 8.0, more preferably 5.5 to 8.0, even more preferably 6.0 to 8.0, particularly preferably 6.5 to 8.0, and most preferably 6.5 to 7.8. When the composition of the present disclosure is a solid composition, the solid composition may, when dissolved in water, form an aqueous solution exhibiting a pH of 5.5 to 10.0 at 25°C and 1 atmospheric pressure, and the pH may be 5.5 to 9.0, preferably 5.3 to 8.0, more preferably 5.5 to 8.0, even more preferably 6.0 to 8.0, particularly preferably 6.5 to 8.0, and most preferably 6.5 to 7.8. When the composition of the present disclosure is a solid composition, for example, the pH of an aqueous solution prepared by mixing water and the solid composition of the present disclosure in a weight ratio of 1:1 to 1:10 may be within the above range.

[0013] 2'FL is a type of human milk oligosaccharide (HMO) and is the most abundant HMO found in breast milk. 2'FL is a neutral trisaccharide consisting of L-fucose, D-galactose, and D-glucose, with the 2'-position of lactose fucosylated. Publicly available 2'FL can be used as the 2'FL contained in the composition of the present disclosure. 2'FL can also be produced by purification from milk or whey, chemical synthesis, enzymatic methods, microbial fermentation, or the like, and can be produced based on the descriptions in, for example, JP 2003-047402 A, WO 2015 / 188834 A, WO 2022 / 176994 A, WO 2012 / 112777 A, WO 2010 / 115935 A, and the like.

[0014] The concentration of 2'FL in the composition of the present disclosure is not particularly limited. When the composition of the present disclosure is a liquid composition, for example, the concentration may be 0.1 mg / ml or more, preferably 0.2 mg / ml or more, more preferably 1 mg / ml or more, and even more preferably 3 mg / ml or more, based on the volume of the composition. When the composition of the present disclosure is a solid composition, the concentration of 2'FL may be 1 mg / ml or more, preferably 2 mg / ml or more, more preferably 10 mg / ml or more, and even more preferably 30 mg / ml or more, based on the volume of the composition. When the composition of the present disclosure is a liquid composition, the concentration of 2'FL may be 100 mg / ml or less, 50 mg / ml or less, 30 mg / ml or less, 10 mg / ml or less, 5 mg / ml or less, 3 mg / ml or less, or 1 mg / ml or less, and preferably 31 mg / ml or less, based on the volume of the composition. When the composition of the present disclosure is a solid composition, the concentration of 2'FL may be, for example, 500 mg / ml or less, 300 mg / ml or less, 100 mg / ml or less, 50 mg / ml or less, 30 mg / ml or less, or 10 mg / ml or less, preferably 310 mg / ml or less.

[0015] When the composition of the present disclosure is a liquid composition, the concentration of 2'FL in the composition of the present disclosure may be, for example, 0.1 mg / ml to 100 mg / ml, 0.2 mg / ml to 100 mg / ml, 0.1 mg / ml to 50 mg / ml, 0.2 mg / ml to 50 mg / ml, 0.1 mg / ml to 31 mg / ml, or 0.2 mg / ml to 31 mg / ml, based on the volume of the composition.

[0016] When the composition of the present disclosure is a solid composition, the concentration of 2'FL in the composition of the present disclosure may be, for example, 1 mg / ml or more and 500 mg / ml or less, 2 mg / ml or more and 500 mg / ml or less, 1 mg / ml or more and 310 mg / ml or less, or 2 mg / ml or more and 310 mg / ml or less, based on the volume of the composition.

[0017] The concentration of 2'FL in the composition of the present disclosure can be measured by the method described in the Examples below. Specific examples of methods for measuring the concentration of 2'FL include ion chromatography (IC) and liquid chromatography / mass spectrometry (LC / MSMS).

[0018] FucGal is a disaccharide consisting of L-fucose and D-galactose, in which the 2'-position of the galactose is fucosylated.

[0019] The concentration of FucGal in the composition of the present disclosure is not particularly limited, but when the composition of the present disclosure is a liquid composition, it may be, for example, 0.01 mg / ml or more, preferably 0.02 mg / ml or more, more preferably 0.05 mg / ml or more, even more preferably 0.1 mg / ml or more, and particularly preferably 1 mg / ml or more, based on the volume of the composition. When the composition of the present disclosure is a solid composition, the concentration of FucGal in the composition of the present disclosure may be, for example, 0.1 mg / ml or more, preferably 0.2 mg / ml or more, more preferably 0.5 mg / ml or more, even more preferably 1 mg / ml or more, and particularly preferably 10 mg / ml or more, based on the volume of the composition. When the composition of the present disclosure is a liquid composition, the concentration of FucGal in the composition of the present disclosure may be, for example, 50 mg / ml or less, 40 mg / ml or less, 25 mg / ml or less, 10 mg / ml or less, 5 mg / ml or less, 3 mg / ml or less, or 1 mg / ml or less, based on the volume of the composition. When the composition of the present disclosure is a solid composition, the concentration of FucGal in the composition of the present disclosure may be, for example, 500 mg / ml or less, 400 mg / ml or less, 250 mg / ml or less, 100 mg / ml or less, 50 mg / ml or less, 30 mg / ml or less, or 10 mg / ml or less, based on the volume of the composition.

[0020] When the composition of the present disclosure is a liquid composition, the concentration of FucGal in the composition of the present disclosure may be, for example, based on the volume of the composition, 0.01 mg / ml to 50 mg / ml, 0.02 mg / ml to 50 mg / ml, 0.01 mg / ml to 40 mg / ml, 0.02 mg / ml to 40 mg / ml, 0.1 mg / ml to 40 mg / ml, 0.01 mg / ml to 25 mg / ml, or 0.02 mg / ml to 25 mg / ml.

[0021] When the composition of the present disclosure is a solid composition, the concentration of FucGal in the composition of the present disclosure may be, for example, 0.1 mg / ml to 500 mg / ml, 0.2 mg / ml to 500 mg / ml, 0.1 mg / ml to 400 mg / ml, 0.2 mg / ml to 400 mg / ml, 0.1 mg / ml to 250 mg / ml, or 0.2 mg / ml to 250 mg / ml, based on the volume of the composition.

[0022] The concentration of FucGal in the composition of the present disclosure can be measured by the method described in the Examples below. Specific examples of methods for measuring the concentration of FucGal include ion chromatography (IC) and liquid chromatography-mass spectrometry (LC / MSMS). Generally available FucGal can be used as a standard substance when measuring the concentration of FucGal in the composition of the present disclosure.

[0023] When the composition of the present disclosure is a liquid composition containing water, the total concentration of 2′FL and FucGal in the liquid composition may be 0.01 mg / ml or more and 50 mg / ml or less.When the composition of the present disclosure is a solid composition, the total concentration of 2′FL and FucGal in the solid composition may be 0.1 mg / ml or more and 500 mg / ml or less.

[0024] The composition of the present disclosure may further contain a compound containing a phosphorus atom. Examples of the compound containing a phosphorus atom include phosphorus chloride, phosphorus oxide, phosphoric acid, and phosphates. The compound containing a phosphorus atom may be phosphoric acid, phosphates, or a combination thereof. The composition containing a compound containing a phosphorus atom may be prepared by adding the compound containing a phosphorus atom itself as a food additive or the like, or by adding a raw material containing a compound containing a phosphorus atom, such as milk, lactic acid bacteria, soy milk, vegetables, fruits, barley, tea leaves, or black tea leaves.

[0025] The phosphorus concentration in the composition of the present disclosure is not particularly limited, and may be, for example, 0.05 mg / ml or more, preferably 0.065 mg / ml or more, more preferably 0.1 mg / ml or more, even more preferably 0.25 mg / ml or more, 0.55 mg / ml or more, particularly preferably 1 mg / ml or more, and most preferably 15 mg / ml or more, based on the volume of the composition. The phosphorus concentration in the composition of the present disclosure may be, for example, 200 mg / ml or less, 150 mg / ml or less, 100 mg / ml or less, 50 mg / ml or less, 30 mg / ml or less, 15.5 mg / ml or less, or 10 mg / ml or less, based on the volume of the composition. Here, in the present disclosure, "phosphorus concentration" refers to the concentration of phosphorus atoms contained in the composition of the present disclosure.

[0026] The phosphorus concentration contained in the composition of the present disclosure may be, for example, based on the volume of the composition, from 0.05 mg / ml to 200 mg / ml, from 0.065 mg / ml to 200 mg / ml, from 0.1 mg / ml to 200 mg / ml, from 0.25 mg / ml to 200 mg / ml, from 0.55 mg / ml to 200 mg / ml, from 1 mg / ml to 200 mg / ml, from 0.05 mg / ml to 150 mg / ml, from 0.065 mg / ml to 150 mg / ml, from 0.1 mg / ml to 150 mg / ml, or from 0 mg / ml to 200 mg / ml. .. 25mg / ml to 150mg / ml, 0.55mg / ml to 150mg / ml, 1mg / ml to 150mg / ml, 0.05mg / ml to 100mg / ml, 0.065mg / ml to 100mg / ml, 0.1mg / ml or more 100mg / ml or less, 0.25mg / ml or more and 100mg / ml or less, 0.55mg / ml or more and 100mg / ml or less, 1mg / ml or more and 100mg / ml or less, 0.05mg / ml or more and 50mg / ml or less, 0.065mg / ml or more and 50mg / ml or less, 0.1 mg / ml to 50 mg / ml, 0.25 mg / ml to 50 mg / ml, 0.55 mg / ml to 50 mg / ml, 1 mg / ml to 50 mg / ml, 0.05 mg / ml to 30 mg / ml, 0.065 mg / ml to 30 mg / ml or less, 0.1 mg / ml to 30 mg / ml, 0.25 mg / ml to 30 mg / ml, 0.55 mg / ml to 30 mg / ml, 1 mg / ml to 30 mg / ml, 0.05 mg / ml to 15.5 mg / ml, 0.065 mg / ml The concentration may be from 0.05 mg / ml to 10 mg / ml, from 0.065 mg / ml to 10 mg / ml, from 0.1 mg / ml to 10 mg / ml, from 0.25 mg / ml to 15.5 mg / ml, from 0.55 mg / ml to 15.5 mg / ml, from 1 mg / ml to 15.5 mg / ml, from 0.05 mg / ml to 10 mg / ml, from 0.065 mg / ml to 10 mg / ml, from 0.1 mg / ml to 10 mg / ml, from 0.25 mg / ml to 10 mg / ml, from 0.55 mg / ml to 10 mg / ml, or from 1 mg / ml to 10 mg / ml.

[0027] The phosphorus concentration in the composition of the present disclosure can be measured, for example, by ion chromatography (IC), the method described in Section 11. Phosphorus 11-1. Inductively coupled plasma atomic emission spectrometry in the Analysis Manual for the 2020 Edition (8th revision) of the Standard Tables of Food Composition in Japan (February 2022), or the method described in Section 21. Phosphorus (1) vanadomolybdic acid absorptiometry, or (2) molybdenum blue absorptiometry in the Appendix to the Food Labeling Standards (November 7, 2023) of the Food Labeling Standards (No. 580).

[0028] The composition of the present disclosure may further contain at least one compound selected from the group consisting of citric acid, citrate salts, acetic acid, acetate salts, phosphoric acid, and phosphate salts, and preferably contains phosphoric acid or a phosphate salt. These can function as a component that forms a buffer to adjust the pH of the composition within a predetermined range. Phosphoric acid and phosphate salts can correspond to the above-mentioned compounds containing a phosphorus atom.

[0029] Subjects to which the compositions of the present disclosure can be administered or ingested include humans and non-human mammals, preferably humans, including, for example, mice, rats, guinea pigs, hamsters, rabbits, cats, dogs, sheep, pigs, cows, horses, goats, and monkeys.

[0030] The human subject to which the composition of the present disclosure is administered or ingested is not limited by gender, age, race, country, region, etc., and may be any of adults, elderly people, children, infants, and newborns, preferably infants or newborns. In another embodiment, the human subject to which the composition of the present disclosure is administered or ingested may be an adult or elderly person.

[0031] The compositions of the present disclosure can be administered or ingested orally or parenterally, but are preferably administered or ingested orally.

[0032] The composition of the present disclosure may be an oral composition, examples of which include foods, food additives, pharmaceuticals, etc. The composition of the present disclosure is preferably a food for special dietary uses, a health functional food, or a general food, and particularly preferably an infant food or general beverage. The composition of the present disclosure may also be a breast milk fortifier. A breast milk fortifier is a pharmaceutical or food intended to be added to breast milk and ingested by an infant for the purpose of increasing the nutritional value of the breast milk. The general beverage is preferably a beverage other than alcoholic beverages or a concentrate thereof, more preferably a milk beverage, a soft drink, or a lactic acid bacteria beverage. The soft drink is preferably a tea beverage, black tea beverage, coffee beverage, cocoa beverage, carbonated beverage, fruit juice beverage, vegetable beverage, sports drink, etc. From the viewpoint of containing a larger amount of compounds containing a phosphorus atom, the beverage is more preferably a milk beverage or a lactic acid bacteria beverage. The infant food may preferably be infant formula. The infant formula may be an infant formula, a baby formula, a follow-up milk, a follow-on milk, or a follow-up formula. The infant formula may be liquid milk or powdered milk.

[0033] When the composition of the present disclosure is a food or food additive, the food or food additive may contain, in addition to the above-mentioned 2'FL and FucGal, ingredients that are typically used in foods or food additives. The food or food additive of the present disclosure may contain bases, carriers, additives, etc. that are typically used in foods or food additives. Examples of additives include excipients, oils, powders, buffers, solubilizers, antioxidants, surfactants, thickeners, preservatives, chelating agents, stabilizers, irritation reducers, antiseptics, colorants, flavorings, alcohols, water-soluble polymers, film-forming agents, resins, etc. The bases, carriers, and various additives described above may be used alone or in combination as needed.

[0034] When the composition of the present disclosure is a liquid composition, the water contained in the composition may be water itself, or may be water contained in an aqueous solution such as a buffer solution (e.g., acetate buffer, citrate buffer, phosphate buffer, etc.) or a beverage (e.g., milk beverage, lactic acid bacteria beverage, etc.).

[0035] When the composition of the present disclosure is a solid composition, there are no particular limitations on the form, and it may be, for example, powder, granules, or the like.

[0036] One example of a method for producing a composition containing 2'-fucosyllactose and 2'-fucosylgalactose of the present disclosure (hereinafter also referred to as the "production method of the present disclosure") is a liquid composition containing water and exhibiting a pH of 5.5 to 10.0 (hereinafter also simply referred to as the "liquid composition"), or a solid composition that forms an aqueous solution exhibiting a pH of 5.5 to 10.0 when dissolved in water (hereinafter also simply referred to as the "solid composition"), and includes heating a composition containing 2'-fucosyllactose to produce 2'-fucosylgalactose in the composition. The substances and forms that can be contained in the liquid composition and solid composition are as described above. The heating may be performed for the purpose of sterilizing microorganisms in the composition, providing a warm beverage (hot beverage), etc. Hereinafter, the liquid composition and the solid composition will be collectively referred to as the "composition."

[0037] The liquid composition may have a pH of 5.5 to 10.0 under an environment of 25°C and 1 atmosphere, and the pH may be 5.5 to 9.0, preferably 5.5 to 8.0, more preferably 6.0 to 7.5, even more preferably 6.5 to 7.5, and even more preferably 6.5 to 7.0. In another embodiment, the pH is preferably 5.5 to 8.0, more preferably 6.5 to 8.0, and even more preferably 7.5 to 8.0. In another embodiment, the pH is preferably 5.5 to 7.5, more preferably 6.0 to 7.0, and even more preferably 6.5 to 7.0. The solid composition may have a pH similar to that of the liquid composition.

[0038] The 2'FL concentration in the composition may be, for example, 0.05 mg / ml or more or 0.1 mg / ml or more, preferably 0.5 mg / ml or more, more preferably 0.9 mg / ml or more, even more preferably 5 mg / ml or more, even more preferably 10 mg / ml or more, and most preferably 25 mg / ml or more, based on the volume of the aqueous solution. The 2'FL concentration in the aqueous solution may be, for example, 500 mg / ml or less, 300 mg / ml or less, 100 mg / ml or less, 85 mg / ml or less, 50 mg / ml or less, 30 mg / ml or less, or 10 mg / ml or less, based on the volume of the aqueous solution.

[0039] The 2'FL concentration in the composition may be, for example, based on the volume of the aqueous solution, from 0.05 mg / ml to 500 mg / ml, from 0.1 mg / ml to 500 mg / ml, from 0.5 mg / ml to 500 mg / ml, from 0.9 mg / ml to 500 mg / ml, from 0.05 mg / ml to 300 mg / ml, from 0.1 mg / ml to 300 mg / ml, from 0.5 mg / ml to 300 mg / ml, from 0.9 mg / ml to 300 mg / ml, from 0.05 mg / ml to 100 mg / ml, from 0.1 mg / ml to 100 mg / ml, from 0.5 mg / ml to 100 mg / ml, . It may be from 0.9 mg / ml to 100 mg / ml, from 0.05 mg / ml to 85 mg / ml, from 0.1 mg / ml to 85 mg / ml, from 0.5 mg / ml to 85 mg / ml, from 0.9 mg / ml to 85 mg / ml, from 0.05 mg / ml to 50 mg / ml, from 0.1 mg / ml to 50 mg / ml, from 0.5 mg / ml to 50 mg / ml, from 0.9 mg / ml to 50 mg / ml, from 0.05 mg / ml to 30 mg / ml, from 0.1 mg / ml to 30 mg / ml, from 0.5 mg / ml to 30 mg / ml, or from 0.9 mg / ml to 30 mg / ml.

[0040] The concentration of 2'-fucosylgalactose relative to the concentration of 2'-fucosyllactose in the composition of the present disclosure may be 0.5% or more, preferably 1% or more, more preferably 5% or more, and even more preferably 10% or more.

[0041] The heating temperature when the composition is heated is not particularly limited, and may be, for example, 60° C. or higher, 70° C. or higher, 80° C. or higher, 90° C. or higher, 96° C. or higher, 97° C. or higher, or 100° C. or higher, or may be 130° C. or lower, 125° C. or lower, 120° C. or lower, 110° C. or lower, 105° C. or lower, or 100° C. or lower. The higher the heating temperature when the composition is heated, the more efficiently FucGal is produced. The heating temperature when heating the composition may be, for example, 60°C or higher and 130°C or lower, 70°C or higher and 130°C or lower, 80°C or higher and 130°C or lower, 90°C or higher and 130°C or lower, 96°C or higher and 130°C or lower, 97°C or higher and 130°C or lower, 100°C or higher and 130°C or lower, 60°C or higher and 125°C or lower, 70°C or higher and 125°C or lower, 80°C or higher and 125°C or lower, 90°C or higher and 125°C or lower, 96°C or higher and 125°C or lower, 97°C or higher and 125°C or lower, 100°C or higher and 125°C or lower, 60°C or higher and 120°C or lower, 70°C or higher and 120°C or lower, 80°C or higher and 120°C or lower, 90°C or higher and 120°C or lower, 96°C or higher and 120°C or lower, 97°C or higher and 120°C or lower, The temperature may be 100°C or higher and 120°C or lower, 60°C or higher and 110°C or lower, 70°C or higher and 110°C or lower, 80°C or higher and 110°C or lower, 90°C or higher and 110°C or lower, 96°C or higher and 110°C or lower, 97°C or higher and 110°C or lower, 100°C or higher and 110°C or lower, 60°C or higher and 105°C or lower, 70°C or higher and 105°C or lower, 80°C or higher and 105°C or lower, 90°C or higher and 105°C or lower, 96°C or higher and 105°C or lower, 97°C or higher and 105°C or lower, 100°C or higher and 105°C or lower, 60°C or higher and 100°C or lower, 70°C or higher and 100°C or lower, 80°C or higher and 100°C or lower, 90°C or higher and 100°C or lower, 96°C or higher and 100°C or lower, or 97°C or higher and 100°C or lower.

[0042] The heating time for heating the composition may be appropriately set depending on the volume of the composition, the heating temperature, etc., and may be, for example, 0.1 second or more, 1 second or more, 30 seconds or more, 1 minute or more, 4 minutes or more, 6 minutes or more, 8 minutes or more, 10 minutes or more, 15 minutes or more, 20 minutes or more, 25 minutes or more, 30 minutes or more, 35 minutes or more, or 40 minutes or more, or may be 150 minutes or less, 140 minutes or less, 130 minutes or less, 120 minutes or less, 110 minutes or less, 100 minutes or less, 90 minutes or less, 80 minutes or less, 70 minutes or less, 60 minutes or less, or 50 minutes or less. The longer the heating time for heating the composition, the more efficiently FucGal is produced. The heating time when heating the composition may be, for example, 30 seconds or more and 90 minutes or less, 1 minute or more and 90 minutes or less, 4 minutes or more and 90 minutes or less, 10 minutes or more and 90 minutes or less, 15 minutes or more and 90 minutes or less, 20 minutes or more and 90 minutes or less, 30 minutes or more and 90 minutes or less, 30 seconds or more and 80 minutes or less, 1 minute or more and 80 minutes or less, 4 minutes or more and 80 minutes or less, 10 minutes or more and 80 minutes or less, 15 minutes or more and 80 minutes or less, 20 minutes or more and 80 minutes or less, 30 minutes or more and 80 minutes or less, 30 seconds or more and 70 minutes or less, 1 minute or more and 70 minutes or less, 4 minutes or more and 70 minutes or less, The time may be 10 minutes or more and 70 minutes or less, 15 minutes or more and 70 minutes or less, 20 minutes or more and 70 minutes or less, 30 minutes or more and 70 minutes or less, 30 seconds or more and 60 minutes or less, 1 minute or more and 60 minutes or less, 4 minutes or more and 60 minutes or less, 10 minutes or more and 60 minutes or less, 15 minutes or more and 60 minutes or less, 20 minutes or more and 60 minutes or less, 30 minutes or more and 60 minutes or less, 30 seconds or more and 50 minutes or less, 1 minute or more and 50 minutes or less, 4 minutes or more and 50 minutes or less, 10 minutes or more and 50 minutes or less, 15 minutes or more and 50 minutes or less, 20 minutes or more and 50 minutes or less, or 30 minutes or more and 50 minutes or less.

[0043] The heating conditions for heating the composition are not limited, but may be, for example, 60°C for 10 minutes or more, preferably 100°C or 105°C for 40 minutes or more, and more preferably 120°C for 4 minutes or more, 10 minutes or more, 20 minutes or more, or 30 minutes or more.

[0044] In the manufacturing method of the present disclosure, the composition may be heated so that the concentration of 2'-fucosylgalactose (mg / ml) in the composition after heating is 1% or more, 3% or more, 5% or more, 10% or more, 15% or more, 20% or more, 23% or more, 30% or more, 35% or more, or 40% or more of the concentration of 2'-fucosyllactose (mg / ml) in the composition before heating. Also, in the manufacturing method of the present disclosure, the composition may be heated so that the concentration of 2'-fucosylgalactose (mg / ml) in the composition after heating is 100% or less, 98% or less, 90% or less, 80% or less, 70% or less, 60% or less, or 50% or less of the concentration of 2'-fucosyllactose (mg / ml) in the composition before heating.

[0045] In the manufacturing method of the present disclosure, the heating of the composition is carried out such that the concentration (mg / ml) of 2'-fucosylgalactose in the composition after heating is, for example, 1% to 100%, 3% to 100%, 5% to 100%, 10% to 100%, 15% to 100%, or 20% to 100% of the concentration (mg / ml) of 2'-fucosyllactose in the composition before heating. , 23% to 100%, 30% to 100%, 35% to 100%, 40% to 100%, 1% to 98%, 3% to 98%, 5% to 98%, 10% to 98% , 15% to 98%, 20% to 98%, 23% to 98%, 30% to 98%, 35% to 98%, 1% to 90%, 3% to 90%, 5% to 90%, 10% or more Upper 90%, 15% to 90%, 20% to 90%, 23% to 90%, 30% to 90%, 35% to 90%, 1% to 80%, 3% to 80%, 5% to 80% Below, 10% to 80%, 15% to 80%, 20% to 80%, 23% to 80%, 30% to 80%, 1% to 70%, 3% to 70%, 5% to 70%, 10 The composition may be heated to a pH of from 1 to 70%, from 15 to 70%, from 20 to 70%, from 23 to 70%, from 1 to 60%, from 3 to 60%, from 5 to 60%, from 10 to 60%, from 15 to 60%, from 20 to 60%, from 1 to 50%, from 3 to 50%, from 5 to 50%, from 10 to 50%, or from 15 to 50%.

[0046] The composition may further contain a compound containing a phosphorus atom. Specific examples of the compound containing a phosphorus atom are as described above. When the composition further contains a compound containing a phosphorus atom, the phosphorus concentration in the composition before heating may be 0.05 mg / ml or more, preferably 0.065 mg / ml or more, more preferably 0.1 mg / ml or more, even more preferably 0.25 mg / ml or more, 0.55 mg / ml or more, particularly preferably 1 mg / ml or more, and most preferably 15 mg / ml or more, based on the volume of the composition. The phosphorus concentration in the composition may be, for example, 200 mg / ml or less, 150 mg / ml or less, 100 mg / ml or less, 50 mg / ml or less, 30 mg / ml or less, 15.5 mg / ml or less, or 10 mg / ml or less, based on the volume of the composition.

[0047] When the composition further contains a compound containing a phosphorus atom, the phosphorus concentration in the composition before heating may be, for example, based on the volume of the composition, 0.05 mg / ml to 200 mg / ml, 0.065 mg / ml to 200 mg / ml, 0.1 mg / ml to 200 mg / ml, 0.25 mg / ml to 200 mg / ml, 0.55 mg / ml to 200 mg / ml, 1 mg / ml to 200 mg / ml, 0.05 mg / ml to 150 mg / ml, 0.065 mg / ml to 150 mg / ml, or mg / ml or less, 0.1 mg / ml or more and 150 mg / ml or less, 0.25 mg / ml or more and 150 mg / ml or less, 0.55 mg / ml or more and 150 mg / ml or less, 1 mg / ml or more and 150 mg / ml or less, 0.05 mg / ml or more and 100 mg / ml or less, 0. 065mg / ml to 100mg / ml, 0.1mg / ml to 100mg / ml, 0.25mg / ml to 100mg / ml, 0.55mg / ml to 100mg / ml, 1mg / ml to 100mg / ml, 0.05mg / ml or more 50mg / ml or less, 0.065mg / ml or more and 50mg / ml or less, 0.1mg / ml or more and 50mg / ml or less, 0.25mg / ml or more and 50mg / ml or less, 0.55mg / ml or more and 50mg / ml or less, 1mg / ml or more and 50mg / ml or less, 0.05 mg / ml to 30 mg / ml, 0.065 mg / ml to 30 mg / ml, 0.1 mg / ml to 30 mg / ml, 0.25 mg / ml to 30 mg / ml, 0.55 mg / ml to 30 mg / ml, 1 mg / ml to 30 mg / ml or less, 0.05 mg / ml to 15.5 mg / ml, 0.065 mg / ml to 15.5 mg / ml, 0.1 mg / ml to 15.5 mg / ml, 0.25 mg / ml to 15.5 mg / ml, 0.55 mg / ml to 15.5 mg / ml, 0.05 mg / ml to 10 mg / ml, 0.065 mg / ml to 10 mg / ml, 0.1 mg / ml to 10 mg / ml, 0.25 mg / ml to 10 mg / ml, or 0.55 mg / ml to 10 mg / ml.

[0048] When the liquid composition is heated, the production method of the present disclosure may further include drying the heated composition to obtain a solid composition. Examples of methods for drying the heated composition include freeze-drying, spray-drying, and heat drying. When dissolved in water, the obtained solid composition forms an aqueous solution exhibiting a pH of 5.5 to 10.0 at 25°C and 1 atmosphere.

[0049] An example of a method for increasing the concentration of 2'-fucosylgalactose in a composition containing 2'-fucosyllactose of the present disclosure (hereinafter also referred to as the "method of the present disclosure") includes heating a composition containing 2'-fucosyllactose, which is a liquid composition containing water and having a pH of 5.5 to 10.0, or a solid composition that forms an aqueous solution having a pH of 5.5 to 10.0 when dissolved in water.

[0050] The increase in the concentration of 2'-fucosyllactose in the composition containing 2'-fucosyllactose of the present disclosure can be confirmed by measuring the concentration of FucGal using the method described in the Examples below. Specifically, the FucGal concentration measured for the composition containing 2'-fucosyllactose before heating is compared with the FucGal concentration measured for the composition containing 2'-fucosyllactose after heating, and if the latter is greater, it can be confirmed that the concentration of the composition containing 2'-fucosyllactose has increased.

[0051] The liquid composition of the present disclosure, which contains water and has a pH of 5.5 to 10.0, or the solid composition that forms an aqueous solution having a pH of 5.5 to 10.0 when dissolved in water, and which contains 2'-fucosyllactose, can be applied without limitation to the above-mentioned composition in the manufacturing method of the present disclosure. The heating of the composition in the method of the present disclosure can also be applied without limitation to the heating of the composition in the manufacturing method of the present disclosure.

[0052] The present invention is not limited to the following examples.

[0053] 1. Preparation of various solutions Infant milk Commercially available powdered infant milk and follow-up powdered milk were dissolved in hot water according to the prescribed preparation method to prepare infant milk and follow-up milk in liquid volumes equivalent to 0.9 times the specified volume.

[0054] Phosphate buffer: 0.5 M aqueous solution of disodium hydrogen phosphate and 0.5 M aqueous solution of monosodium dihydrogen phosphate were mixed to a predetermined pH to prepare 0.5 M phosphate buffer. 0.1, 0.005, and 0.003 M phosphate buffers were also prepared in the same manner.

[0055] 1 / 10 Concentration Mcllvaine Buffer A 0.02 M aqueous solution of disodium hydrogen phosphate and a 0.01 M aqueous solution of citric acid were mixed to a predetermined pH to prepare a 1 / 10 concentration Mcllvaine buffer.

[0056] 0.1 M Citrate Buffer A 0.1 M aqueous solution of citric acid and a 0.1 M aqueous solution of trisodium citrate were mixed to a predetermined pH to prepare a 0.1 M citrate buffer.

[0057] 0.1 M Acetic Acid Buffer A 0.1 M aqueous solution of acetic acid and a 0.1 M aqueous solution of sodium acetate were mixed to a predetermined pH to prepare a 0.1 M acetate buffer.

[0058] 2'FL Aqueous Solution 2'FL (Kyowa Hakko Bio Co., Ltd.) was dissolved in Milli-Q water to prepare 2'FL aqueous solutions with concentrations of 1 mg / ml or 30 mg / ml.

[0059] 2. Method for Quantifying 2'FL and FucGal Concentrations (1) Ion Chromatography (IC) Method For samples in tests using infant formula, the sample was dissolved and diluted in Milli-Q water, and the resulting aqueous solution was passed through an Amicon Ultra 10 kDa filter (Merck) to obtain a sample solution for analysis. For samples in tests other than those using infant formula, the sample was dissolved and diluted in Milli-Q water, and the resulting aqueous solution was passed through a 0.2 μm membrane filter (Advantec) to obtain a sample solution for analysis. The appropriately diluted sample solution was analyzed by ion chromatography under the following conditions. The concentrations were converted using the calibration curve method. 2'FL manufactured by Kyowa Hakko Bio Co., Ltd. and 2'FL manufactured by Dextra Laboratories, Ltd. were used as standard reagents. FucGal (Blood group H disaccharide, 2-O-α-L-Fucopyranosyl-D-galactose) manufactured by Sigma-Aldrich Co., Ltd. was used.

[0060] Ion chromatography conditions: Instrument: ICS-6000DC DIONEX (Thermo Fisher Scientific) Detector: Pulsed amperometry detector Column: Dionex CarboPac PA1 IC Standard Bore Analytical Column, inner diameter 4 mm, length 250 mm, particle size 10 m, Cat# 035391 (Thermo Fisher Scientific) Guard column: Dionex CarboPac PA1 IC Standard Bore Analytical Column, inner diameter 4 mm, length 50 mm, particle size 10 m, Cat# 043096 (Thermo Fisher (manufactured by Scientific) Column temperature: 30°C Flow rate: 1.0 ml / min Injection volume: 25 μl Mobile phase A: Milli-Q water Mobile phase C: 0.3 M aqueous sodium acetate solution Mobile phase D: 0.5 M aqueous sodium hydroxide solution Gradient conditions: Table 1

[0061]

[0062] (2) Liquid Chromatography Mass Spectrometry (LC / MSMS) Method For samples in tests using infant formula, the sample was dissolved and diluted in Milli-Q water, and the resulting aqueous solution was passed through an Amicon Ultra 10 kDa filter (Merck) to obtain a sample solution for analysis. For samples in tests other than those using infant formula, the sample was dissolved and diluted in Milli-Q water, and the resulting aqueous solution was passed through a 0.2 μm membrane filter (Advantec) to obtain a sample solution for analysis. The appropriately diluted sample solution was analyzed by LC / MSMS under the following conditions. The concentration was converted using the calibration curve method. Standard reagents used were 2'FL (Kyowa Hakko Bio Co., Ltd.) and 2'FL (Dextra Laboratories, Ltd.). FucGal (Blood group H disaccharide, (2-O-α-L-Fucopyranosyl-D-galactose)) manufactured by Sigma-Aldrich Co., Ltd. was used.

[0063] LC / MSMS conditions Mass spectrometer: 4500QTRAP (manufactured by AB Sciex) LC device: Agilent 1260 infinity (manufactured by Agilent Technologies) Column: Shodex HILICpak VN-50 4D, φ4.6 × 150 mm (manufactured by Resonaq Co., Ltd.) Column: Shodex HILICpak VN-50G 4D, φ4.6 × 10 mm (manufactured by Resonaq Co., Ltd.) Column temperature: 40°C Flow rate: 1.0 ml / min Injection volume: 5 μl Mobile phase A: 25 mM ammonium formate aqueous solution Mobile phase B: acetonitrile Gradient conditions: Table 2

[0064]

[0065] Ionization method: ESI (negative ion detection mode) Polarity: Negative CUR: 30.00 IS: -4500.00 TEM: 600.00 GS1: 60.00 GS2: 60.00 CAD: 9.00 Set mass number (m / z): See Table 3 below

[0066]

[0067] DP is an abbreviation for declustering potential, EP is an entrance potential, CE is a collision energy, and CXP is a cell exit potential.

[0068] Example 1: pH Comparison Mcllvaine buffers at 1 / 10 concentration were prepared at pH 3.0, 4.0, 4.5, 5.0, 6.0, 7.0, or 7.8, and 2'FL aqueous solutions were added to them to a final 2'FL concentration of 1 mg / ml. The resulting solutions were heated at 120°C for 30 minutes. The 2'FL and FucGal concentrations in the solutions before and after heating were analyzed using IC. The ratio (%) of the 2'FL or FucGal concentration in each heated solution to the 2'FL concentration in each solution before heating (hereinafter also referred to as "ratio of concentration before heating") was calculated. The ratio (%) of the FucGal concentration in each heated solution to the 2'FL concentration in each heated solution (hereinafter also referred to as "ratio of 2'FL concentration after heating") was also calculated.

[0069] The analytical results of the 2'FL concentration and FucGal concentration are shown in Table 4. In Table 4, the values ​​in parentheses in the buffer column indicate the phosphorus concentration in the solution. It was confirmed that heating a solution containing 2'FL produced FucGal in each of the solutions at pH 6.0, 7.0, and 7.8, and that the higher the pH of the solution, the higher the FucGal concentration after heating.

[0070]

[0071] Example 2: Comparison of Heating Temperatures 2'FL solution was added to a 1 / 10 concentration Mcllvaine buffer (phosphorus concentration 0.443 mg / ml) at pH 7.0 so that the final concentration of 2'FL was 10 mg / ml. The resulting solution was heated at 120°C for 4 minutes or 120°C for 30 minutes. The 2'FL and FucGal concentrations in each solution before and after heating were analyzed by IC method. The concentration ratio of 2'FL or FucGal to 2'FL before heating was calculated. The concentration ratio of FucGal to 2'FL after heating was calculated.

[0072] The analytical results of 2'FL concentration and FucGal concentration are shown in Table 5. It was confirmed that FucGal was produced under all heating conditions, and that the shorter the heating time, the higher the FucGal concentration after heating.

[0073]

[0074] Example 3: Comparison of Buffer Types A 1 / 10 concentration Mcllvaine buffer (phosphate concentration 0.443 mg / ml) at pH 7.0, a 0.1 M (3.1 mg / ml) phosphate buffer at pH 7.0, a 0.1 M citrate buffer at pH 7.0, or a 0.1 M acetate buffer at pH 7.0 was prepared, and a 2'FL solution was added to each buffer to a final 2'FL concentration of 10 mg / ml. The resulting solutions were heated at 120°C for 30 minutes. The 2'FL and FucGal concentrations in each solution before and after heating were analyzed using the IC method. The concentration ratios of 2'FL or FucGal to 2'FL before heating were calculated. The concentration ratios of FucGal to 2'FL after heating were calculated.

[0075] The analytical results of 2'FL concentration and FucGal concentration are shown in Table 6. It was confirmed that FucGal was produced in all buffers by heating a pH 7.0 buffer containing 2'FL, and that the FucGal concentration was particularly high after heating a 0.1 M phosphate buffer containing 2'FL at pH 7.0.

[0076]

[0077] Example 4: Comparison of Phosphorus Concentrations 0.003 M (0.093 mg / ml), 0.005 M (0.155 mg / ml), 0.1 M (3.1 mg / ml), or 0.5 M (15.5 mg / ml) phosphate buffers at pH 7.0 were prepared, and 2'FL solution was added to these to a final 2'FL concentration of 30 mg / ml. The resulting solutions were heated at 120°C for 30 minutes. For comparison, a solution obtained using phosphate-free Milli-Q water instead of the buffer was similarly heated. The pH of the Milli-Q water used was 7.4. The 2'FL and FucGal concentrations in each solution before and after heating were analyzed by LC / MSMS. The concentration ratios of 2'FL or FucGal to those before heating were calculated. The concentration ratios of FucGal to 2'FL after heating were calculated.

[0078] The analytical results of the 2'FL concentration and FucGal concentration are shown in Table 7. In Table 7, the values ​​in parentheses in the buffer column indicate the phosphorus concentration in the solution. It was confirmed that heating phosphate buffer containing 2'FL produced FucGal in phosphate buffers of all phosphorus concentrations, and that the higher the phosphorus concentration in the phosphate buffer, the higher the FucGal concentration after heating.

[0079]

[0080] Example 5: Comparison of 2'FL Concentration A 2'FL solution was added to a 0.5 M (15.5 mg / ml) phosphate buffer at pH 7.0 so that the final concentration of 2'FL was 1 mg / ml, 30 mg / ml, or 100 mg / ml. The resulting solution was heated at 120°C for 30 minutes. The 2'FL and FucGal concentrations in the solution before and after heating were analyzed by LC / MSMS. The concentration ratios of 2'FL or FucGal to 2'FL before heating were calculated. The concentration ratios of FucGal to 2'FL after heating were calculated.

[0081] The analytical results of the 2'FL concentration and FucGal concentration are shown in Table 8. It was confirmed that heating a solution containing 2'FL produced FucGal at any 2'FL concentration, and that the higher the 2'FL concentration in the solution, the higher the FucGal concentration after heating.

[0082]

[0083] Example 6: Comparison of phosphorus origins Infant milk, follow-up milk, or 0.005 M phosphate buffer at pH 7.0 was prepared, and a 2'FL solution was added to each to a final 2'FL concentration of 30 mg / ml. The resulting solutions were heated at 120°C for 30 minutes. The 2'FL and FucGal concentrations in each solution before and after heating were analyzed by LC / MSMS. The concentration ratios of 2'FL or FucGal to 2'FL before heating were calculated. The concentration ratios of FucGal to 2'FL after heating were calculated.

[0084] Table 9 shows the analytical results for 2'FL and FucGal concentrations. The phosphorus concentrations in the infant formulas were calculated from the nutritional information of each product. It was confirmed that heating solutions containing 2'FL produced FucGal in all solutions. The phosphorus contained in infant formulas is thought to be derived from the raw milk. It has been reported that compounds containing phosphorus atoms exist in cow's milk as calcium phosphate or phosphoproteins (Milk Science Vol. 54, No. 1 2005). Phosphorus-containing compounds also exist as phospholipids. This suggests that phosphorus contributes to the production of FucGal regardless of its origin or form.

[0085]

[0086] Example 7: Phosphate Buffer Addition Test for Infant Milk The amount of FucGal produced when phosphate buffer was added to infant milk to achieve a phosphorus concentration equivalent to that of follow-up milk was evaluated. Specifically, 0.009M phosphate buffer was added to infant milk with a phosphorus concentration of 0.009M to prepare infant milk with a phosphorus concentration equivalent to that of 0.018M follow-up milk. A 2'FL solution was then added to the infant milk to a final 2'FL concentration of 30 mg / ml. The resulting solution was heated at 120°C for 30 minutes. For comparison, infant milk or follow-up milk was heated in the same manner. The 2'FL and FucGal concentrations in each solution before and after heating were analyzed using LC / MSMS. The concentration ratios of 2'FL or FucGal to those before heating were calculated. The concentration ratios of FucGal to 2'FL after heating were calculated.

[0087] Table 10 shows the analytical results for 2'FL and FucGal concentrations. The FucGal concentrations in the heated solutions were similar between the infant formula with 0.009M phosphate buffer and the follow-up milk. These results suggest that the amount of FucGal produced by heating in infant formula containing 2'FL also depends on the phosphorus concentration. Furthermore, the results for the infant formula with phosphate buffer reproduced the FucGal production by heating in infant formula.

[0088]

[0089] Example 8: Comparison of heating times using infant formula 2'FL solution was added to infant formula or follow-up formula so that the final concentration of 2'FL was 1 mg / ml or 30 mg / ml. The resulting solution was heated at 120°C for 4 minutes or 30 minutes. The 2'FL and FucGal concentrations in each solution before and after heating were analyzed by LC / MSMS. The concentration ratios of 2'FL or FucGal to those before heating were calculated. The concentration ratios of FucGal to 2'FL after heating were calculated.

[0090] The analytical results of 2'FL concentration and FucGal concentration are shown in Table 11. It was confirmed that heating infant formula containing 2'FL produced FucGal in all infant formulas, and that the longer the heating time in infant formula, the higher the FucGal concentration.

[0091]

[0092] Example 9: Comparison of heating conditions using phosphate buffer A 2'FL solution was added to a 0.5 M (15.5 mg / ml) phosphate buffer at pH 7.0 so that the final concentration of 2'FL was 30 mg / ml. The resulting solution was heated at 120°C for 4 minutes, 120°C for 30 minutes, or 105°C for 40 minutes. The 2'FL and FucGal concentrations in each solution before and after heating were analyzed by LC / MSMS. The concentration ratios of 2'FL or FucGal to 2'FL before heating were calculated. The concentration ratios of FucGal to 2'FL after heating were calculated.

[0093] The analytical results of the 2'FL concentration and FucGal concentration are shown in Table 12. Heating a pH 7.0 phosphate buffer containing 2'FL produced FucGal in all solutions, and it was shown that the higher the heating temperature and time, the higher the FucGal concentration after heating, even when a pH 7.0 phosphate buffer was used.

[0094]

[0095] Example 10: FucGal production test using a commercially available green tea beverage A 2'FL solution was added to Milli-Q water or a commercially available green tea beverage so that the final concentration of 2'FL was 30 mg / ml. The resulting solution was heated at 120°C for 30 minutes. The 2'FL and FucGal concentrations in the solution before and after heating were analyzed by LC / MSMS. The concentration ratio of 2'FL or FucGal to the concentration before heating was calculated. The concentration ratio of FucGal to 2'FL after heating was calculated. Note that Milli-Q water contains almost no phosphorus, and commercially available green tea beverages contain only about 0.01 mg / ml.

[0096] Table 13 shows the analytical results of 2'FL concentration and FucGal concentration. Heating of solutions containing 2'FL produced FucGal in all solutions. However, the amount of FucGal produced in Milli-Q water and commercial green tea beverages was lower than in solutions containing higher amounts of phosphorus (0.05 mg / ml or higher) as shown in Examples 4 to 9. This indicates that solutions with phosphorus concentrations of 0.05 mg / ml or higher produce more FucGal upon heating than solutions with phosphorus concentrations less than 0.05 mg / ml.

[0097]

[0098] Example 11: Comparison of Heating Temperatures 2'FL solution was added to a 1 / 10 concentration Mcllvaine buffer (phosphorus concentration 0.443 mg / ml) at pH 7.0 so that the final 2'FL concentration was 8.67 mg / ml. The resulting solution was either not heated or heated at 125°C for 20 minutes. The 2'FL and FucGal concentrations in each solution before and after heating were analyzed by IC method. The FucGal concentration ratio to 2'FL after heating was calculated.

[0099] Table 14 shows the analytical results of 2'FL concentration and FucGal concentration. It was confirmed that FucGal was produced even under heating conditions of 125°C for 20 minutes, and that the higher the heating temperature, the higher the FucGal concentration after heating. When the solution obtained in Example 11 was heated at 125°C for 20 minutes, the FucGal concentration was the same (0.8 mg / ml) compared to when the solution obtained in Example 1 at pH 7.0 was heated at 120°C for 30 minutes, despite the solution obtained in Example 11 having a lower pre-heating 2'FL concentration. Furthermore, when the solution obtained in Example 11 was heated at 125°C for 20 minutes, the FucGal to 2'FL concentration ratio after heating was higher than when the solution obtained in Example 1 at pH 7.0 was heated at 120°C for 30 minutes, and FucGal was produced more efficiently.

[0100]

Claims

1. A liquid composition containing water and exhibiting a pH of 5.5 to 10.0, or a solid composition which forms an aqueous solution exhibiting a pH of 5.5 to 10.0 when dissolved in water, comprising 2'-fucosyllactose and 2'-fucosylgalactose.

2. The composition of claim 1, wherein the concentration of the 2'-fucosylgalactose is 0.01 mg / ml or more based on the volume of the composition.

3. The composition of claim 1, wherein the concentration of the 2'-fucosyllactose is 0.1 mg / ml or more based on the volume of the composition.

4. The composition according to claim 1, wherein the concentration of 2'-fucosylgalactose is 0.5% or more relative to the concentration of 2'-fucosyllactose.

5. The composition of claim 1, wherein the composition further comprises a compound containing a phosphorus atom, and the concentration of phosphorus in the composition is 0.05 mg / ml or more based on the volume of the composition.

6. The composition of claim 1, further comprising at least one compound selected from the group consisting of citric acid, citrate salts, acetic acid, acetate salts, phosphoric acid, and phosphate salts.

7. The composition according to any one of claims 1 to 6, which is a beverage.

8. The composition according to claim 7, wherein the beverage is a milk beverage or a lactic acid bacteria beverage.

9. A composition according to any one of claims 1 to 6, which is an infant food or a breast milk fortifier.

10. A method for producing a composition containing 2'-fucosyllactose and 2'-fucosylgalactose, which comprises heating a liquid composition containing water and exhibiting a pH of 5.5 to 10.0, or a solid composition which forms an aqueous solution exhibiting a pH of 5.5 to 10.0 when dissolved in water, the composition containing 2'-fucosyllactose, to produce 2'-fucosylgalactose in the composition.

11. The method according to claim 10, wherein the composition is heated so that the concentration (mg / ml) of 2'-fucosylgalactose in the composition after heating is 1% or more of the concentration (mg / ml) of 2'-fucosyllactose in the composition before heating.

12. The method according to claim 10 or 11, wherein 2'-fucosylgalactose is produced in the composition by heating the composition at 60°C or higher for 10 minutes or longer.

13. The method of claim 10 or 11, wherein the concentration of 2'-fucosyllactose in the composition before heating is 0.1 mg / ml or more.

14. The method of claim 10 or 11, wherein the composition further comprises a compound containing a phosphorus atom, and the phosphorus concentration in the composition before heating is 0.05 mg / ml or more.

15. A method for increasing the concentration of 2'-fucosylgalactose in a composition containing 2'-fucosyllactose, the method comprising heating the composition, which is a liquid composition containing water and exhibiting a pH of 5.5 to 10.0, or a solid composition which, when dissolved in water, forms an aqueous solution exhibiting a pH of 5.5 to 10.0, and which contains 2'-fucosyllactose.

16. The method of claim 15, wherein the composition is heated so that the concentration (mg / ml) of 2'-fucosylgalactose in the composition after heating is 1% or more of the concentration (mg / ml) of 2'-fucosyllactose in the composition before heating.

17. The method of claim 15 or 16, wherein the composition is heated to 60°C or higher for 10 minutes or more.

18. The method of claim 15 or 16, wherein the concentration of the 2'-fucosyllactose in the composition before heating is 0.1 mg / ml or more.

19. The method of claim 15 or 16, wherein the composition further comprises a compound containing a phosphorus atom, and the phosphorus concentration in the composition before heating is 0.05 mg / ml or more.

Images