WO2019130499A1 - Vitamin-b-group-compound-containing acidic composition demonstrating excellent vitamin b group compound stability - Google Patents

Vitamin-b-group-compound-containing acidic composition demonstrating excellent vitamin b group compound stability Download PDF

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Publication number
WO2019130499A1
WO2019130499A1 PCT/JP2017/047020 JP2017047020W WO2019130499A1 WO 2019130499 A1 WO2019130499 A1 WO 2019130499A1 JP 2017047020 W JP2017047020 W JP 2017047020W WO 2019130499 A1 WO2019130499 A1 WO 2019130499A1
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Prior art keywords
vitamin
less
composition
ethanol
group
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PCT/JP2017/047020
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French (fr)
Japanese (ja)
Inventor
香織 喜田
朝武　宗明
亮介 石田
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ハウスウェルネスフーズ株式会社
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Priority claimed from JP2017247340A external-priority patent/JP7036504B2/en
Priority claimed from JP2017247336A external-priority patent/JP7036503B2/en
Application filed by ハウスウェルネスフーズ株式会社 filed Critical ハウスウェルネスフーズ株式会社
Priority to CN201780097697.0A priority Critical patent/CN111511220A/en
Publication of WO2019130499A1 publication Critical patent/WO2019130499A1/en

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation

Definitions

  • the decomposition rate of one or more vitamin B group compounds selected from the group consisting of folic acid, vitamin B 12 and biotin is reduced, and / or the stability of the vitamin B group compounds is excellent.
  • the present invention relates to an acidic composition containing the above-mentioned vitamin B group compound.
  • Folic acid is one of the vital vitamins, and folic acid functions as a coenzyme in vivo and is involved in protein biosynthesis and the like.
  • folate deficiency can result in a variety of diseases and disorders (eg, megaloblastic anemia, neuropathy, intestinal dysfunction, etc.).
  • diseases and disorders eg, megaloblastic anemia, neuropathy, intestinal dysfunction, etc.
  • fetal neural tube abnormalities that can be caused by maternal nutritional deficiency can be prevented by administering folic acid, and that folic acid has a protective effect against cancer, particularly epithelial cancer.
  • the recommended intake of folate is 240 ⁇ g / day for adults, 480 ⁇ g / day for pregnant women, and 340 ⁇ g / day for lactating women It is supposed to be the day.
  • folic acid is contained in various foods, almost half of folic acid in foods is eliminated by cooking and heating, so a large amount of food must be consumed to obtain the above recommended intake, which is not easy. Absent.
  • Patent Documents 1 and 2 disclose a method for improving the stability of folic acid in an acidic aqueous solution by complexing folic acid with lactoferrin.
  • Patent Document 2 discloses a beverage containing folic acid containing a benzoic acid which is a preservative, by blending an inorganic salt or an organic salt of one or more metals selected from the group consisting of calcium, copper, and zinc. Techniques are disclosed to improve the stability of folic acid.
  • ⁇ About vitamin B 12 > Vitamin B 12 is a kind of vitamins B.
  • Vitamin B 12 is closely related to nervous function, and is effective in improving neurological symptoms such as eye strain, muscle pain, joint pain (stiff shoulders, back pain, etc.), neuralgia, numbness of the hands and feet, etc.
  • a composition containing 12 is marketed.
  • Patent Document 3 discloses an internally-administered liquid preparation whose pH is adjusted to 5.8 to 7.5 in order to improve the stability of both vitamin B 1 and vitamin B 12 .
  • Patent Document 4 discloses a complex vitamin internal solution prepared by adding a sugar alcohol and adjusting the pH to 3.5 to 4.5 in order to improve the stability of both vitamin B 1 and vitamin B 12 There is.
  • Patent Document 5 discloses that one cyanocobalamin of vitamin B 12 is unstable in an aqueous solution having a pH of 7.0 to 7.5, but can be stabilized by incorporating taurine. There is.
  • Patent Document 6 describes the problem that vitamin B 12 is decomposed when it is blended with other vitamins such as vitamin B 1 , B 2 , B 6 , ascorbic acid, and the content is reduced. Then, as means for solving the problem in Patent Document 6, vitamin B 12 deposited on an inert support, vitamin B 12 containing composition is disclosed which is formed by covering the surrounding inert saccharide.
  • Patent Document 7 is characterized in that, as a stable vitamin B 12 preparation, a composition in which vitamin E particles containing vitamin B 12 are dispersed in starch is further dispersed in calcium silicate. Powdered compositions are described.
  • Biotin is a kind of vitamin B group and is also called vitamin H or coenzyme E. Biotin catalyzes the carboxylation reaction in vivo as a coenzyme of carboxylase. The carboxylation reaction is involved in gluconeogenesis, branched chain amino acids, fatty acid synthesis, energy metabolism and the like. Compositions incorporating biotin have been marketed.
  • Patent document 8 improves the stability of biotin by further blending vitamin C into a solution containing biotin and vitamin B2 in order to solve the problem that biotin is easily decomposed under vitamin B2 coexistence conditions. Is described.
  • Patent Document 9 describes that the stability of biotin is improved by further blending a toshishi extract into a solution containing biotin and vitamin B2.
  • Patent Document 10 describes that it may be preferable to incorporate a sugar alcohol as a sweetening agent because biotin is unstable in the presence of a reducing sugar (eg, sugar) in a liquid preparation for internal use.
  • a sugar alcohol e.g, sugar
  • Patent Document 11 when biotin is incorporated into an internal solution having a pH of 2 to 5 containing a sweetener such as sugar, the biotin is decomposed. Therefore, by adding the Stevia extract as a sweetener, biotin can be stabilized. Have been described.
  • Patent Document 12 describes that biotin is stabilized by containing sucralose in an internal solution containing biotin.
  • Patent Document 13 describes that biotin is stabilized by containing polyvinyl pyrrolidone in a biotin-containing aqueous internal solution.
  • Patent No. 4339979 JP 2011-55828 A JP 2001-72594 A JP 7-112933 A Japanese Examined Patent Publication No. 63-40168 JP, 2016-27007, A JP 2007-182386 A JP, 2017-95372, A JP, 2006-89430, A Japanese Patent Application Laid-Open No. 10-265369 JP-A-9-104625 JP 2001-10955 A JP-A-7-76520
  • Patent Documents 1 and 2 and Non-Patent Documents 1 to 3 are premised on blending lactoferrin and benzoic acids with folic acid in the composition, and applications and forms of supplements and beverages.
  • Patent Documents 1 and 2 and Non-Patent Documents 1 to 3 are premised on blending lactoferrin and benzoic acids with folic acid in the composition, and applications and forms of supplements and beverages.
  • Patent Documents 8 to 13 presuppose that other components are added to the composition together with biotin for stabilization, and the use and form of supplements and beverages are limited. There is a possibility that There remains a need in the art for techniques to improve the stability of biotin in acidic compositions.
  • the decomposition rate of one or more vitamin B group compounds selected from the group consisting of folic acid, vitamin B 12 and biotin is reduced, and / or the stability of the vitamin B group compounds is excellent. It aims at providing the acidic composition containing the said vitamin-B group compound.
  • one or more vitamin B group compounds selected from the group consisting of folic acid, vitamin B 12 and biotin in an acidic composition is ethanol Was found to increase its degradation rate and / or decrease its stability. Also, by reducing the amount of ethanol present in the acidic composition, the degradation rate of one or more vitamin B-group compounds selected from the group consisting of folic acid, vitamin B 12 and biotin is reduced, and / Or it discovered that the stability improved.
  • the present invention is based on these findings and includes the following inventions.
  • An acidic composition containing one or more selected from the group consisting of folic acid, vitamin B 12 and biotin, characterized in that the content of ethanol is less than 0.1% by weight object.
  • the composition according to [1] wherein the total content of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine is less than 0.1% by weight in total.
  • the composition according to [2] wherein the content of the protic organic solvent is less than 0.1% by weight in total.
  • [5] A method for producing an acidic composition containing one or more selected from the group consisting of folic acid, vitamin B 12 and biotin, which contains raw materials such that the amount of ethanol is less than 0.1% by weight How to do that.
  • the method according to [5] which comprises blending the raw materials so that the total amount of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine is less than 0.1% by weight.
  • the method according to [6] which comprises blending the raw materials so that the total amount of protic organic solvent is less than 0.1% by weight.
  • [8] The method according to any one of [5] to [7], wherein the composition is a container-packed beverage or a container-packed jelly beverage.
  • a method for improving the stability of one or more selected from the group consisting of folic acid, vitamin B 12 and biotin in an acidic composition comprising 0.1% of the amount of ethanol contained in the composition
  • a method comprising including less than weight percent.
  • the method according to [9] comprising bringing the amounts of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine in total into the composition below 0.1% by weight in total.
  • the method according to [10] wherein the total amount of the protic organic solvent contained in the composition is less than 0.1% by weight.
  • the method according to any one of [9] to [11], wherein the composition is a container-packed beverage or a container-packed jelly beverage.
  • the present specification includes the disclosure contents of Japanese Patent Application No. 2017-247336 and Japanese Patent Application No. 2017-247340 based on which the priority of the present application is based.
  • the decomposition rate of one or more vitamin B group compounds selected from the group consisting of folic acid, vitamin B 12 and biotin is reduced, and / or the stability of the vitamin B group compounds is excellent.
  • the acidic composition containing said vitamin-B group compound can be provided. According to the present invention, it is possible to provide an acidic composition containing the above-mentioned vitamin B group compound which is excellent in storage stability and capable of efficiently ingesting the above-mentioned vitamin B group compound.
  • the present invention relates to an acidic composition
  • an acidic composition comprising one or more vitamin B-group compounds selected from the group consisting of folic acid, vitamin B 12 and biotin, and having a reduced content of ethanol.
  • vitamin B compound or “the aforementioned vitamin B compound” is, unless otherwise specified, one or more vitamins selected from the group consisting of folic acid, vitamin B 12 and biotin. "Group B compound”.
  • the one or more vitamin B group compounds selected from the group consisting of folic acid, vitamin B 12 and biotin is folic acid.
  • folic acid, one or more vitamin B group compound is selected from the group consisting of vitamin B 12 and biotin is vitamin B 12.
  • folic acid, one or more vitamin B group compound is selected from the group consisting of vitamin B 12 and biotin is vitamin B 12.
  • composition of the present invention is an acidic composition characterized by containing folic acid and having a reduced content of ethanol.
  • compositions of the present invention is an acidic composition, characterized in that contain vitamin B 12, and the content of ethanol is reduced.
  • composition of the present invention is an acidic composition characterized by containing biotin and having a reduced content of ethanol.
  • folic acid is one of the water-soluble vitamins of the vitamin B complex, and is a compound represented by the following structural formula called pteroyl monoglutamic acid,
  • the derivative means a derivative thereof or a salt thereof which is acceptable in medicines, food and drink.
  • the derivative include, but are not limited to, a polyglutamic acid type in which a plurality of glutamic acids are bound, and the like.
  • Folic acid may be extracted or purified from food, or may be chemically synthesized.
  • the food containing folic acid is not particularly limited, but vegetables such as asparagus, broccoli, spinach, green soybeans, broad bean, corn, cabbage, kale, quill garlic, sun gins, etc., litchi, strawberry, mango, avocado, durian, etc. There can be mentioned fruits and meats such as avian, bovine and porcine liver.
  • the synthesis method of folic acid is to be carried out based on a known method (eighth edition food additive standard document, pages D-1655 to D-1660, Kamogawa Shoten Co., Ltd., published on December 10, 2007).
  • the composition of the present invention in one embodiment, comprises folic acid.
  • Folic acid can be suitably included in the composition of the embodiment containing folic acid in an amount selected from the range of 0.1 ppm to 10 ppm, preferably 1 ppm to 10 ppm, more preferably 1 ppm to 5 ppm.
  • the composition of the present embodiment has 100 ⁇ g or more, 150 ⁇ g or more, 200 ⁇ g or more, 240 ⁇ g or more, 250 ⁇ g or more, 300 ⁇ g or more, 350 ⁇ g or more, 400 ⁇ g or more, 450 ⁇ g or more, or 500 ⁇ g or more of folic acid per single oral intake. It can be suitably contained in the range of 550 ⁇ g or more.
  • a range including the intake (day) of folic acid recommended in "Japanese food intake criteria (2015 version)" published by MHLW is preferable.
  • the upper limit of the amount of folic acid contained per single oral intake is not particularly limited, and can be appropriately determined, for example, from the range of 1000 ⁇ g or less, 900 ⁇ g or less, 800 ⁇ g or less, 700 ⁇ g or less, 600 ⁇ g or less.
  • a single oral intake refers to an amount at which the composition is orally ingested at one time, or continuously at short time intervals (eg, a time of 10 minutes or less, preferably 5 minutes or less). It means the total amount taken orally in several times.
  • 50 mL to 500 mL typically 50 mL, 100 mL, 150 mL, 180 mL, 200 mL, 250 mL, 300 mL, 350 mL, 400 mL, 450 mL or 500 mL is the volume.
  • vitamin B 12 is one of the water-soluble vitamins of the vitamin B complex, and is a generic term for vitamins including cobalt.
  • Vitamin B 12 includes, hydroxocobalamin, adenosyl cobalamin, methylcobalamin, cyanocobalamin, sulfite cobalamin or its derivative or a salt thereof acceptable in the pharmaceutical and food products, as a specific compound.
  • Vitamin B 12 may be extracted or purified from food, may be produced by a microorganism, or may be chemically synthesized.
  • the food containing vitamin B 12 is not particularly limited, but fish such as oyster, shijimi, salmon roe, saury and lice, meat such as avian, bovine and porcine liver can be mentioned.
  • Cyanocobalamin of vitamin B 12 is Actinomycetes (Streptomyces) or bacteria (genus Agrobacterium, the genus Bacillus, Flavobacterium, the genus Propionibacterium, Rhizobium) may be separated from the culture medium, such as be able to.
  • compositions of the present invention in one embodiment, vitamin B 12.
  • the composition of the embodiment containing vitamin B 12 is selected from the range of 0.001 ppm to 5 ppm, preferably 0.005 ppm to 0.5 ppm, more preferably 0.01 ppm to 0.05 ppm of vitamin B 12 It can be included appropriately in the amount.
  • the composition of the present embodiment has 0.9 ⁇ g or more, 1.0 ⁇ g or more, 1.2 ⁇ g or more, 1.5 ⁇ g or more, 1.8 ⁇ g or more, 2.0 ⁇ g or more of vitamin B 12 per single oral intake.
  • a range including the intake amount (day) of vitamin B 12 recommended by the “Japanese food intake standard (2015 version)” published by MHLW is preferable.
  • the upper limit of the amount of vitamin B 12 contained in a single oral intake is not particularly limited. For example, it may be appropriately determined from the range of 10 ⁇ g or less, 9 ⁇ g or less, 8 ⁇ g or less, 7 ⁇ g or less, 5 ⁇ g or less, 4 ⁇ g or less it can.
  • biotin is one of the essential water-soluble vitamins, and is a compound represented by the following structural formula:
  • Biotin may be extracted or purified from food, or may be chemically synthesized.
  • the food containing biotin is not particularly limited, but can be bovine liver, egg yolk, beans such as soybeans and grains.
  • the composition of the present invention in one embodiment, comprises biotin.
  • the composition of the embodiment containing biotin suitably contains biotin in an amount selected from the range of 0.001 ppm to 10 ppm, preferably 0.01 ppm to 1 ppm, more preferably 0.2 ppm to 0.3 ppm.
  • the composition of the present invention contains 10 ⁇ g or more, 15 ⁇ g or more, 20 ⁇ g or more, 25 ⁇ g or more, 30 ⁇ g or more, 35 ⁇ g or more, 40 ⁇ g or more, 45 ⁇ g or more, 50 ⁇ g or more, 60 ⁇ g or more of 70 ⁇ g of biotin per single oral intake.
  • the range of 100 ⁇ g or more can be suitably included in the range of 100 ⁇ g or more.
  • a range that includes the intake amount (day) of biotin recommended in “Japanese food intake criteria (2015 version)” published by the Ministry of Health, Labor and Welfare is preferable.
  • the upper limit of the amount of biotin contained per single oral intake is not particularly limited, and can be appropriately determined, for example, from 1000 ⁇ g or less, 500 ⁇ g or less, 400 ⁇ g or less, 300 ⁇ g or less, 200 ⁇ g or less, 150 ⁇ g or less.
  • protic organic solvent means an organic solvent which dissociates by itself to generate a proton, and has an atom of high electronegativity, that is, a hydrogen atom bonded to a nitrogen atom or an oxygen atom
  • protic organic solvents include, but are not limited to, lower alcohols (ethanol, methanol), glycerin, acetic acid, formic acid, butylamine and the like.
  • ethanol has the effect of increasing the rate of degradation of the Group B vitamin compound in the acidic composition. Therefore, by reducing the amount of ethanol contained in the acidic composition, the degradation rate of the vitamin B group compound in the acidic composition can be reduced, and the preservation of the vitamin B group compound in the acidic composition It can improve stability.
  • ethanol not only ethanol, but also the protic organic solvents glycerin, methanol, acetic acid, formic acid and butylamine as well as ethanol have an effect of increasing the decomposition rate of the vitamin B group compound, so preferably in an acidic composition
  • reducing the total amount of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine contained therein it is possible to reduce the decomposition rate of the vitamin B group compound in the acidic composition, The storage stability of the group B compound can be enhanced.
  • the vitamin B group compound in the acidic composition is reduced by reducing the total amount of protic organic solvents (including ethanol, glycerin, methanol, acetic acid, formic acid, butylamine and the like) contained in the acidic composition.
  • the decomposition rate of the compound can be reduced, and the storage stability of the group B vitamin compound in the acidic composition can be enhanced.
  • the amount of ethanol contained in the composition of the present invention is preferably reduced as much as possible in order to reduce the decomposition rate of the vitamin B group compound and / or enhance storage stability, and is included in the composition.
  • the storage stability of the vitamin B group compound in the composition can be enhanced.
  • the amount of ethanol contained in the composition of the present invention may be small as compared to the amount of ethanol in the conventional acidic composition containing the vitamin B group compound, and is not particularly limited.
  • it may be in the range of less than 0.1 wt%, for example, less than 0.09 wt%, less than 0.08 wt%, less than 0.07 wt%, or less than 0.06 wt%. Particularly preferably, it can be in the range of 0.05 wt% or less, 0.04 wt% or less, 0.03 wt% or less, 0.02 wt% or less, or 0.01 wt% or less.
  • the total amount of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine in the composition of the present invention is possible to further reduce the decomposition rate of the group B compound and / or to further enhance the storage stability. It is preferable to reduce as much as possible.
  • the total amount of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine in the composition of the present invention may be a small amount as compared to the total amount in the conventional acidic composition containing the vitamin B group compound, although not particularly limited, specifically, it is less than 0.1 wt%, for example, less than 0.09 wt%, less than 0.08 wt%, less than 0.07 wt%, or less than 0.06 wt% It can be in the range of Particularly preferably, it can be in the range of 0.05 wt% or less, 0.04 wt% or less, 0.03 wt% or less, 0.02 wt% or less, or 0.01 wt% or less.
  • the total amount of the protic organic solvent in the composition of the present invention including ethanol, glycerin, methanol, acetic acid, formic acid, butylamine and the like further reduces the decomposition rate of the vitamin B group compound and / or storage stability It is preferable to reduce as much as possible to further enhance the
  • the total amount of the protic organic solvent in the composition of the present invention may be a small amount as compared to the total amount in the conventional acidic composition containing the vitamin B group compound, and is not particularly limited. In particular, it may be in the range of less than 0.1% by weight, such as less than 0.09% by weight, less than 0.08% by weight, less than 0.07% by weight, or less than 0.06% by weight. . Particularly preferably, it can be in the range of 0.05 wt% or less, 0.04 wt% or less, 0.03 wt% or less, 0.02 wt% or less, or 0.01 wt% or less.
  • ethanol is not only those which are compounded in the process of producing the acidic composition of the present invention, respectively. Also included are those which are incorporated / contaminated in the process of producing the raw materials used for producing the composition. For example, ethanol is contained in almost all types of perfume formulations today (Uematsu et al., Food Safety Journal, Vol. 38, No. 6, pp. 452-459, December, 1997).
  • the diluent blended in the final product is displayed but may not be displayed in the case of the solvent used for extracting the perfume, and there are also many types of compounds when formulating the perfume formulation.
  • the solvent contained in the fragrance before mixing may not be displayed because the fragrance is mixed. For this reason, even if there is no indication that ethanol is included in the perfume formulation, it may actually be included, and when such a perfume formulation is blended in the composition of the present invention, it may be in the composition. Can increase the ethanol content of to increase the degradation rate of the group B compound.
  • the amounts of “ethanol”, “ethanol, glycerin, methanol, acetic acid, formic acid and butylamine” and “protic organic solvent” in the composition of the present invention are each measured by a commonly known conventional method. Is possible.
  • the content of each solvent component in the composition is obtained by mixing the composition with anhydrous sodium sulfate and acetonitrile, filtering it, and using the solution obtained by dissolving the obtained filtrate in acetonitrile as an analysis sample, gas chromatography It can be determined by adding it to the index (Kenji Isshiki, Food Safety. Vol. 26, No. 1, pp. 39-45, 1985).
  • the "acidic composition” means a composition having a pH value of 4.5 or less, for example, less than 4.5, less than 4.4, less than 4.3, less than 4.2, pH 4 Less than 1, less than pH 4.0, less than pH 3.9, less than pH 3.8, less than pH 3.7, less than pH 3.6, less than pH 3.5, less than pH 3.4, or less than pH 3.3 .
  • the lower limit of the pH value is not particularly limited, and can be appropriately determined according to the form of the acidic composition. For example, pH 2.5 or more, pH 2.6 or more, pH 2.7 or more, pH 2.8 or more, pH 2 .9 or more, pH 3.0 or more, pH 3.1 or more, or pH 3.2 or more.
  • the pH value is preferably less than pH 4.0.
  • the methods for sterilization and sterilization of soft drinks are largely different at pH 4.0, and those below pH 4.0 have a core temperature of 65 ° C. While it is required to heat for 10 minutes, sterilization of pH 4.0 or more is required to heat the core temperature at 85 ° C. for 30 minutes. Therefore, by setting the upper limit of the pH value to less than pH 4.0, the load by the sterilization step can be reduced, and the decomposition of the vitamin B group compound in the sterilization step can be reduced, which is preferable.
  • pH value points out the value measured by 20 degreeC of substance temperature.
  • the pH value of the acidic composition of the present invention can be adjusted by appropriately adjusting the amount of acidulant added.
  • the acidulant include those generally used in the manufacture of medicines and foods and drinks, and examples thereof include citric acid, malic acid, gluconic acid, tartaric acid, lactic acid, succinic acid, and salts thereof. Or mixtures of two or more can be added.
  • a pharmaceutically or food-acceptable excipient in addition to the vitamin B group compound, a pharmaceutically or food-acceptable excipient, a disintegrant, a lubricant, a binder, an antioxidant, a coloring agent, an aggregation inhibitor Absorption accelerators, solvents, solubilizers, tonicity agents, stabilizers, flavoring agents, pH adjusters, flavor preparations, sweeteners, thickeners, preservatives, vitamins, other raw materials such as agar Can be appropriately selected and blended according to the form desired in the composition.
  • these components do not contain ethanol or that the content of ethanol is low, and do not contain ethanol, glycerin, methanol, acetic acid, formic acid and butylamine, or that their total content is low. It is more preferable to use, and it is particularly preferable to use one which does not contain a protic organic solvent (including ethanol, glycerin, methanol, acetic acid, formic acid, butylamine and the like) or has a low total content of protic organic solvents.
  • a protic organic solvent including ethanol, glycerin, methanol, acetic acid, formic acid, butylamine and the like
  • a perfume preparation that uses one or more selected from medium-chain fatty acids and / or emulsifiers can be included as a solvent instead of ethanol.
  • C8, C10, C12 triglyceride and the like can be used as the medium chain fatty acid, although not particularly limited, and as the emulsifier, glycerin fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, Sucrose fatty acid ester etc. can be utilized.
  • the acidic composition of the present invention can be provided in the form of a pharmaceutical (including quasi drugs) or food and drink. These forms may be in the form of liquid compositions or semisolid compositions (gel-like, sol-like, etc.), and the above-mentioned other raw materials may be added to the vitamin B-group compound according to the dosage form thereof. It can be appropriately blended and prepared according to a conventional method.
  • the acidic composition of the present invention can be a container-packed beverage.
  • a container for containing the acidic composition (liquid composition) of the present invention a container used as a container for beverages can be suitably used, and is not limited, but a container made of polyethylene terephthalate (PET), a so-called PET bottle, And metal can containers.
  • PET polyethylene terephthalate
  • the form of the container is not particularly limited.
  • the volume of the container is not particularly limited, but for example, 50 to 500 mL (typically, 50 to 100 mL, 150 to 180 mL, 200 to 250 mL, 300 to 350, 400 to 450 or 500 mL), preferably 100 to 200 be able to.
  • the acidic composition of the present invention can be a container-packed jelly beverage.
  • the container for containing the acidic composition (semi-solid (gel-like, sol-like, etc.) composition) of the present invention may be a container used as a container for jelly drinks, as appropriate, without limitation.
  • a film and / or a container made of a metal film, a pouch container, etc. may be mentioned.
  • the volume of the container is not particularly limited, but can be, for example, 50 mL to 200 mL (typically, 50 mL, 100 mL, 150 mL, 180 mL, 200 mL).
  • the acidic composition of the present invention is the vitamin B group compound extracted or purified from food, or the chemically synthesized vitamin B group compound, acidulant, and other raw materials as described above as needed, As well as mixing the remainder with water, the content of ethanol is small compared to the content of ethanol in the conventional acidic composition containing the vitamin B group compound, specifically less than 0.1% by weight, for example, Less than 0.09% by weight, less than 0.08% by weight, less than 0.07% by weight, or less than 0.06% by weight, preferably 0.05% by weight or less, 0.04% by weight or less, 0. It can manufacture so that it may become the range of 03 weight% or less, 0.02 weight% or less, or 0.01 weight% or less.
  • the acidic composition according to a more preferred embodiment of the present invention is the vitamin B group compound extracted or purified from food, or the chemically synthesized vitamin B group compound, acidulant, as described above, as needed. And other raw materials, and water as the balance, and the total content of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine is the content of ethanol in the conventional acidic composition containing the vitamin B group compound Smaller amounts, specifically less than 0.1% by weight, for example less than 0.09% by weight, less than 0.08% by weight, less than 0.07% by weight, or less than 0.06% by weight, preferably Is manufactured in a range of 0.05 wt% or less, 0.04 wt% or less, 0.03 wt% or less, 0.02 wt% or less, or 0.01 wt% or less Door can be.
  • the acidic composition according to a particularly preferred embodiment of the present invention is the vitamin B group compound extracted or purified from food, or the chemically synthesized vitamin B group compound, acidulant, as described above, as needed.
  • the total content of the protic organic solvent is compared with the total content of the protic organic solvent in the conventional acidic composition containing the vitamin B group compound Small amounts, specifically less than 0.1% by weight, for example less than 0.09% by weight, less than 0.08% by weight, less than 0.07% by weight, or less than 0.06% by weight, preferably It can be manufactured to have a range of 0.05 wt% or less, 0.04 wt% or less, 0.03 wt% or less, 0.02 wt% or less, or 0.01 wt% or less.
  • Means for containing the acidic composition of the present invention in a container and means for sterilization can be optionally selected.
  • HPLC Measurement After measuring the weight, a solution sample containing folic acid was adjusted to pH 12.0 (pH meter (F-72 manufactured by HORIBA)) using a 1.0 N sodium hydroxide solution (Wako Pure Chemical Industries, Ltd.).
  • the HPLC measurement was performed under the following conditions.
  • Base solution 2.5% by weight of granulated sugar, 1.2% by weight of fructose, 0.8% by weight of L-ascorbic acid, 0.2% by weight of citric acid, 0.2% by weight of trisodium citrate, and ion-exchanged water 0.0003% by weight of folic acid was added, and the pH was adjusted to a predetermined pH using 1.0 N hydrochloric acid (Wako Pure Chemical Industries, Ltd.) and 1.0 N sodium hydroxide (Wako Pure Chemical Industries, Ltd.) to prepare a base solution. II.
  • Test 1 Effect of ethanol addition (1) A solution containing a base solution and ethanol or acetonitrile according to the composition shown in the following Table 1 and having a predetermined pH (Examples 1 to 7, Comparative Examples 1E to 7E (ethanol added), Comparative Examples 1A to 7A (Acetonitrile addition) were each prepared (day 0).
  • Each solution was filled with 100 mL of the solution in a light-shielded retort pouch at room temperature, and then subjected to hot water sterilization (DAUDA thermostatic water tank (D20 KP)) at 80 ° C. for 10 minutes. Next, each solution was stored at 50 ° C. for a predetermined period (ADVANTEC thermostatic chamber (AGX-345)), and the amount of folate in each solution after storage was measured by HPLC.
  • DAUDA thermostatic water tank D20 KP
  • ADVANTEC thermostatic chamber AGX-345
  • Test 2 Effect of ethanol addition (2) According to the composition shown in Table 3 below, solutions (Examples 8 and 9, Comparative Example 8E) containing a base solution and ethanol and having a pH of 3.5 were prepared (Day 0).
  • Each solution was filled in a retort pouch, sterilized, stored as in the above-mentioned test 1, and the amount of folate in each solution after storage was measured by HPLC.
  • Test 3 Effect of ethanol addition (3)
  • solutions containing folic acid (Example 10, Comparative Example 9E) were prepared (Day 0).
  • the fragrance 1 is a solution made by using medium-chain fatty acid and glycerin fatty acid ester as a solvent without containing ethanol
  • the fragrance 2 contains 50% by weight of ethanol as a solvent (final product concentration 0.1% by weight) It is a perfume.
  • ethanol-containing preparations are used as flavoring agents to enhance dispersibility.
  • an ethanol-free perfume ie, to use ethanol-free raw materials, in order to reduce the rate of folic acid degradation and to achieve stabilization.
  • Solid phase column adsorbate was eluted using methanol in a 25 mL pear-shaped flask. After concentration to dryness using a rotary evaporator (Rotavapor (registered trademark) R-210) manufactured by Nippon Buchi, 1 mL of water was added to re-dissolve the residue. The lysate was filtered using a CA filter (MS CA Syringe Filter; diameter 13 mm, pore diameter 0.45 ⁇ m) to give a sample solution.
  • a rotary evaporator Rotavapor (registered trademark) R-210) manufactured by Nippon Buchi
  • Test 4 Each solution having the composition shown in Table 7 was pretreated by the method described in the HPLC measurement pretreatment method as a solution sample containing vitamin B 12 to prepare a sample solution, and the obtained sample solution was subjected to HPLC measurement according to HPLC measurement conditions.
  • the amount of vitamin B 12 was determined from the HPLC measurement value using a calibration curve prepared using a standard solution, and was taken as the value on day 0, and this was taken as 100%.
  • About 100 mL of each solution having the composition shown in Table 7 was filled into a light-shielded retort pouch at room temperature, and then sterilized with hot water at 80 ° C. for 10 minutes using a thermostatic water tank (D20KP) made by LAUDA.
  • Each solution after sterilization was stored at 50 ° C. using a thermostatic container (AGX-345) manufactured by ADVANTEC, and vitamin B 12 was measured on day 0 and day 3 in the same manner.
  • Base solution adjustment method Ion-exchange water to be 2.5% granulated sugar, 1.2% fructose, 1.2% L-ascorbic acid, 0.2% citric acid, 0.2% citric acid, 0.2% trisodium citrate, 0.3 ppm biotin
  • the solution was adjusted to a target pH using 1.0 N hydrochloric acid (Wako Pure Chemical Industries, Ltd.) and 1.0 N sodium hydroxide (Wako Pure Chemical Industries, Ltd.) to obtain a base solution.
  • Test Example 5 The amount of biotin was measured according to the microbiological determination method according to the official method for each solution of the composition shown in Table 9. The measured value of the amount of biotin for each solution was taken as the value on day 0, which was taken as 100%.
  • Comparative Example 1E in which ethanol, which is a proton donating organic solvent, was added promoted the decomposition of biotin in each pH range.
  • Comparative Example 1A in which acetonitrile having substantially the same solubility parameter (SP value, ethanol: 12.7, acetonitrile: 11.9) was added had almost the same decomposition rate as the example. From this, the influence of the solubility of biotin was almost nonexistent, and it was speculated that the acceleration of biotin degradation was caused by the proton donating property from the degradation mechanism of biotin, which is a phenomenon unique to ethanol.

Abstract

The purpose of the present invention is to provide an acidic composition that contains at least one type of vitamin-B-group compound selected from the group that consists of folic acid, vitamin B12, and biotin, the vitamin-B-group compound having excellent stability and/or exhibiting reduced decomposition. An acidic composition that contains the abovementioned vitamin-B-group compound and is characterized by having reduced ethanol content.

Description

ビタミンＢ群化合物の安定性が優れたビタミンＢ群化合物含有酸性組成物Vitamin B group compound-containing acidic composition having excellent stability of vitamin B group compounds
　本発明は、葉酸、ビタミンＢ１２及びビオチンからなる群から選択される１種以上のビタミンＢ群化合物の分解速度が低減されている、及び／又は前記ビタミンＢ群化合物の安定性が優れた、前記ビタミンＢ群化合物を含有する酸性組成物に関する。 In the present invention, the decomposition rate of one or more vitamin B group compounds selected from the group consisting of folic acid, vitamin B 12 and biotin is reduced, and / or the stability of the vitamin B group compounds is excellent. The present invention relates to an acidic composition containing the above-mentioned vitamin B group compound.
＜葉酸について＞
　葉酸は生体必須ビタミンの一つであり、また、葉酸は生体内で補酵素として機能し、タンパク質の生合成等に関与している。このため葉酸の欠乏は様々な疾患や障害（例えば、巨赤芽球性貧血、神経障害、腸機能不全等）を生じ得る。さらに、母体の妊娠時の栄養欠乏により生じ得る胎児の神経管異常は、葉酸を投与することにより予防できること、また葉酸が癌、特に上皮系の癌に対して防御作用を示すことが報告されている（非特許文献１，２）。このため、近年、葉酸の重要性が注目されている。 <About folic acid>
Folic acid is one of the vital vitamins, and folic acid functions as a coenzyme in vivo and is involved in protein biosynthesis and the like. Thus, folate deficiency can result in a variety of diseases and disorders (eg, megaloblastic anemia, neuropathy, intestinal dysfunction, etc.). Furthermore, it has been reported that fetal neural tube abnormalities that can be caused by maternal nutritional deficiency can be prevented by administering folic acid, and that folic acid has a protective effect against cancer, particularly epithelial cancer. (Non-Patent Documents 1 and 2). For this reason, in recent years, the importance of folic acid has been attracting attention.
　厚生労働省が公表する「日本人の食事摂取基準（２０１５年版）」（非特許文献３）によれば、葉酸の推奨摂取量は成人で２４０μｇ／日、妊婦で４８０μｇ／日、授乳婦で３４０μｇ／日とされている。葉酸は様々な食品中に含まれるものの、食品中の葉酸は調理・加熱により半分近くが消失してしまうため、上記推奨摂取量を得るためには大量の食品を摂取しなければならず容易ではない。 According to the Japanese Dietary Intake Standard (2015 version) published by the Ministry of Health, Labor and Welfare, the recommended intake of folate is 240 μg / day for adults, 480 μg / day for pregnant women, and 340 μg / day for lactating women It is supposed to be the day. Although folic acid is contained in various foods, almost half of folic acid in foods is eliminated by cooking and heating, so a large amount of food must be consumed to obtain the above recommended intake, which is not easy. Absent.
　そのため、高濃度の葉酸を含有するサプリメントや飲食品が開発・販売されており、食品を摂取するよりも効率的に上記推奨摂取量の葉酸を摂取できることから人気を博している。特に、その摂取容易性や嗜好品としての面から、高濃度の葉酸を含有する液体タイプのサプリメントや飲料は高い人気を得ている。 Therefore, supplements and food products containing high concentrations of folic acid have been developed and marketed, and have gained popularity because they can ingest the recommended intake amount of folate more efficiently than ingesting food. In particular, liquid-type supplements and beverages containing high concentrations of folate have gained high popularity due to their ease of consumption and as a favorite product.
　一方、葉酸は乾燥状態では安定であるが、水溶液中、特に飲料に適した酸性領域においてはその安定性が低下することが知られている（特許文献１、２）。特許文献１においては、葉酸をラクトフェリンと共に複合体とすることによって、酸性水溶液中における葉酸の安定性を向上させる手法が開示されている。特許文献２には、防腐剤である安息香酸類を配合した葉酸含有飲料に、カルシウム、銅、及び亜鉛からなる群から選ばれる一種以上の金属の無機塩又は有機塩を配合することによって、当該飲料中の葉酸の安定性を向上させる手法が開示されている。
＜ビタミンＢ１２について＞
　ビタミンＢ１２はビタミンＢ群の一種である。ビタミンＢ１２は、神経機能と密接な関係があり、眼精疲労、筋肉痛、関節痛（肩こり、腰痛など）、神経痛、手足のしびれ等の神経症状の改善に効果があることから、ビタミンＢ１２を配合した組成物が上市されている。 On the other hand, it is known that folic acid is stable in a dry state, but its stability decreases in an aqueous solution, particularly in an acidic region suitable for beverages (Patent Documents 1 and 2). Patent Document 1 discloses a method for improving the stability of folic acid in an acidic aqueous solution by complexing folic acid with lactoferrin. Patent Document 2 discloses a beverage containing folic acid containing a benzoic acid which is a preservative, by blending an inorganic salt or an organic salt of one or more metals selected from the group consisting of calcium, copper, and zinc. Techniques are disclosed to improve the stability of folic acid.
<About vitamin B 12 >
Vitamin B 12 is a kind of vitamins B. Vitamin B 12 is closely related to nervous function, and is effective in improving neurological symptoms such as eye strain, muscle pain, joint pain (stiff shoulders, back pain, etc.), neuralgia, numbness of the hands and feet, etc. A composition containing 12 is marketed.
　特許文献３には、ビタミンＢ１とビタミンＢ１２の両方を配合した液剤の保存安定性が悪いこと、その理由が、それぞれの安定ｐＨ領域が異なること、並びに、ビタミンＢ１の分解物がビタミンＢ１２の安定性を低下させること、ビタミンＢ１２がショ糖水溶液中で特に不安定であることが記載されている。そして、特許文献３では、ビタミンＢ１とビタミンＢ１２両方の安定性向上のため、ｐＨを５．８～７．５に調整した内服用液剤が開示されている。 According to Patent Document 3, the storage stability of a solution containing both vitamin B 1 and vitamin B 12 is poor, the reason is that each stable pH range is different, and the decomposition product of vitamin B 1 is a vitamin reducing the stability of the B 12, it has been described that the vitamin B 12 is particularly unstable in aqueous sucrose solution. Patent Document 3 discloses an internally-administered liquid preparation whose pH is adjusted to 5.8 to 7.5 in order to improve the stability of both vitamin B 1 and vitamin B 12 .
　特許文献４には、ビタミンＢ１とビタミンＢ１２の両方の安定性を向上させるため、糖アルコールを添加し、ｐＨを３．５～４．５に調整した、複合ビタミン内服液剤が開示されている。 Patent Document 4 discloses a complex vitamin internal solution prepared by adding a sugar alcohol and adjusting the pH to 3.5 to 4.5 in order to improve the stability of both vitamin B 1 and vitamin B 12 There is.
　特許文献５には、ビタミンＢ１２の１つのシアノコバラミンは、ｐＨ７．０～７．５の水溶液中で安定性が不安定であるが、タウリンを配合することにより安定化されることが開示されている。 Patent Document 5 discloses that one cyanocobalamin of vitamin B 12 is unstable in an aqueous solution having a pH of 7.0 to 7.5, but can be stabilized by incorporating taurine. There is.
　特許文献６には、ビタミンＢ１２は、ビタミンＢ１、Ｂ２、Ｂ６、アスコルビン酸等の他のビタミン類と配合すると分解されて含量が低下するという課題が記載されている。そして、特許文献６ではこの課題を解決するための手段として、ビタミンＢ１２を不活性担体に付着させ、その周囲を不活性糖類で被覆して成るビタミンＢ１２含有組成物が開示されている。 Patent Document 6 describes the problem that vitamin B 12 is decomposed when it is blended with other vitamins such as vitamin B 1 , B 2 , B 6 , ascorbic acid, and the content is reduced. Then, as means for solving the problem in Patent Document 6, vitamin B 12 deposited on an inert support, vitamin B 12 containing composition is disclosed which is formed by covering the surrounding inert saccharide.
　特許文献７には、安定なビタミンＢ１２製剤として、ビタミンＢ１２類を含有するビタミンＥ類粒子がデンプン類中に分散状態にある組成物を、さらにケイ酸カルシウム中に分散させることを特徴とする粉末状組成物が記載されている。
＜ビオチンについて＞
　ビオチンはビタミンＢ群の一種であり、ビタミンＨ又は補酵素Ｅとも称される。ビオチンは、生体内で、カルボキシラーゼの補酵素としてカルボキシル化反応を触媒している。カルボキシル化反応は、糖新生、分岐鎖アミノ酸、脂肪酸合成、エネルギー代謝等に関与する。ビオチンを配合した組成物が上市されている。 Patent Document 7 is characterized in that, as a stable vitamin B 12 preparation, a composition in which vitamin E particles containing vitamin B 12 are dispersed in starch is further dispersed in calcium silicate. Powdered compositions are described.
<About Biotin>
Biotin is a kind of vitamin B group and is also called vitamin H or coenzyme E. Biotin catalyzes the carboxylation reaction in vivo as a coenzyme of carboxylase. The carboxylation reaction is involved in gluconeogenesis, branched chain amino acids, fatty acid synthesis, energy metabolism and the like. Compositions incorporating biotin have been marketed.
　特許文献８には、ビオチンがビタミンＢ２共存条件で分解しやすいという課題を解決するために、ビオチンとビタミンＢ２とを含む液剤に更にビタミンＣを配合することで、ビオチンの安定性を向上させることが記載されている。 Patent document 8 improves the stability of biotin by further blending vitamin C into a solution containing biotin and vitamin B2 in order to solve the problem that biotin is easily decomposed under vitamin B2 coexistence conditions. Is described.
　特許文献９には、ビオチンとビタミンＢ２とを含む液剤に更にトシシ抽出物を配合することで、ビオチンの安定性を向上させることが記載されている。 Patent Document 9 describes that the stability of biotin is improved by further blending a toshishi extract into a solution containing biotin and vitamin B2.
　特許文献１０には、内用液剤においてビオチンが還元糖（例えば砂糖）の存在下では不安定であることから、糖アルコールを甘味剤として配合することが好ましい場合があることが記載されている。 Patent Document 10 describes that it may be preferable to incorporate a sugar alcohol as a sweetening agent because biotin is unstable in the presence of a reducing sugar (eg, sugar) in a liquid preparation for internal use.
　特許文献１１には、砂糖などの甘味料を配合したｐＨ２～５の内服液剤にビオチンを配合するとビオチンが分解することから、甘味料としてステビア抽出物を加えることで、ビオチンを安定化することが記載されている。 According to Patent Document 11, when biotin is incorporated into an internal solution having a pH of 2 to 5 containing a sweetener such as sugar, the biotin is decomposed. Therefore, by adding the Stevia extract as a sweetener, biotin can be stabilized. Have been described.
　特許文献１２には、ビオチンを含有する内服液剤にスクラロースを含有させることで、ビオチンを安定化することが記載されている。 Patent Document 12 describes that biotin is stabilized by containing sucralose in an internal solution containing biotin.
　特許文献１３には、ビオチン含有水性内用液剤にポリビニルピロリドンを含有させることで、ビオチンを安定化することが記載されている。 Patent Document 13 describes that biotin is stabilized by containing polyvinyl pyrrolidone in a biotin-containing aqueous internal solution.
特許第４３３９９７９号公報Patent No. 4339979 特開２０１１－５５８２８号公報JP 2011-55828 A 特開２００１－７２５９４号公報JP 2001-72594 A 特開平７－１１２９３３号公報JP 7-112933 A 特公昭６３－４０１６８号公報Japanese Examined Patent Publication No. 63-40168 特開２０１６－２７００７号公報JP, 2016-27007, A 特開２００７－１８２３８６号公報JP 2007-182386 A 特開２０１７－９５３７２号公報JP, 2017-95372, A 特開２００６－８９４３０号公報JP, 2006-89430, A 特開平１０－２６５３６９号公報Japanese Patent Application Laid-Open No. 10-265369 特開平９－１０４６２５号公報JP-A-9-104625 特開２００１－１０９５５号公報JP 2001-10955 A 特開平７－７６５２０号公報JP-A-7-76520
　特許文献１、２及び非特許文献１～３に記載の葉酸を安定化する手法は、組成物中に葉酸と共に、ラクトフェリンや安息香酸類を配合することを前提としており、サプリメントや飲料の用途・形態が限定されてしまう場合があることから、当該分野においては依然として、酸性水溶液中における葉酸の安定性を向上させることが可能な新たな手段が切望されている。 The methods for stabilizing folic acid described in Patent Documents 1 and 2 and Non-Patent Documents 1 to 3 are premised on blending lactoferrin and benzoic acids with folic acid in the composition, and applications and forms of supplements and beverages. However, there is still a need in the art for new means capable of improving the stability of folic acid in acidic aqueous solutions.
　特許文献３に記載のビタミンＢ１２を安定化する手法では、ビタミンＢ１２の安定化のために内服用液剤のｐＨを５．８～７．５の範囲に調節する必要がある。特許文献４～７に記載のビタミンＢ１２を安定化する手法では、組成物中にビタミンＢ１２と共に、安定化のために他の成分を配合することを前提としており、サプリメントや飲料の用途・形態が限定されてしまう場合がある。当該分野においては依然として、酸性組成物中でのビタミンＢ１２の安定性を向上させる技術が切望されている。 In the method for stabilizing vitamin B 12 described in Patent Document 3, it is necessary to adjust the pH of the liquid preparation to be in the range of 5.8 to 7.5 in order to stabilize vitamin B 12 . The methods for stabilizing vitamin B 12 described in Patent Documents 4 to 7 presuppose that other ingredients are incorporated for stabilization together with vitamin B 12 in the composition, and the use of a supplement or a beverage The form may be limited. There remains a need in the art for techniques to improve the stability of vitamin B 12 in acidic compositions.
　特許文献８～１３に記載のビオチンを安定化する手法では、組成物中にビオチンと共に、安定化のために他の成分を配合することを前提としており、サプリメントや飲料の用途・形態が限定されてしまう場合がある。当該分野においては依然として、酸性組成物中でのビオチンの安定性を向上させる技術が切望されている。 The methods for stabilizing biotin described in Patent Documents 8 to 13 presuppose that other components are added to the composition together with biotin for stabilization, and the use and form of supplements and beverages are limited. There is a possibility that There remains a need in the art for techniques to improve the stability of biotin in acidic compositions.
　そこで本発明は、葉酸、ビタミンＢ１２及びビオチンからなる群から選択される１種以上のビタミンＢ群化合物の分解速度が低減されている、及び／又は前記ビタミンＢ群化合物の安定性が優れた、前記ビタミンＢ群化合物を含有する酸性組成物を提供することを目的とする。 Therefore, according to the present invention, the decomposition rate of one or more vitamin B group compounds selected from the group consisting of folic acid, vitamin B 12 and biotin is reduced, and / or the stability of the vitamin B group compounds is excellent. It aims at providing the acidic composition containing the said vitamin-B group compound.
　本発明者らは、上記課題を解決するために鋭意検討を重ねた結果、酸性組成物中における葉酸、ビタミンＢ１２及びビオチンからなる群から選択される１種以上のビタミンＢ群化合物は、エタノールが存在することによって、その分解速度が増大すること、及び／又はその安定性が低下することを見出した。また、酸性組成物中に存在するエタノールの量を低減させることによって、葉酸、ビタミンＢ１２及びビオチンからなる群から選択される１種以上のビタミンＢ群化合物の分解速度が低減すること、及び／又はその安定性が向上することを見出した。 As a result of intensive studies to solve the above problems, the present inventors have found that one or more vitamin B group compounds selected from the group consisting of folic acid, vitamin B 12 and biotin in an acidic composition is ethanol Was found to increase its degradation rate and / or decrease its stability. Also, by reducing the amount of ethanol present in the acidic composition, the degradation rate of one or more vitamin B-group compounds selected from the group consisting of folic acid, vitamin B 12 and biotin is reduced, and / Or it discovered that the stability improved.
　本発明はこれらの知見に基づくものであり、以下の発明を包含する。
［１］葉酸、ビタミンＢ１２及びビオチンからなる群から選択される１種以上を含有する酸性組成物であって、エタノールの含有量が０．１重量％未満であることを特徴とする、組成物。
［２］エタノール、グリセリン、メタノール、酢酸、ギ酸及びブチルアミンの含有量が合計で０．１重量％未満である、［１］に記載の組成物。
［３］プロトン性有機溶媒の含有量が合計で０．１重量％未満である、［２］に記載の組成物。
［４］容器詰め飲料又は容器詰めゼリー飲料である、［１］～［３］のいずれかに記載の組成物。
［５］葉酸、ビタミンＢ１２及びビオチンからなる群から選択される１種以上を含有する酸性組成物の製造方法であって、エタノールの量が０．１重量％未満となるように原材料を配合することを含む、方法。
［６］エタノール、グリセリン、メタノール、酢酸、ギ酸及びブチルアミンの量が合計で０．１重量％未満となるように原材料を配合することを含む、［５］に記載の方法。
［７］プロトン性有機溶媒の量が合計で０．１重量％未満となるように原材料を配合することを含む、［６］に記載の方法。
［８］前記組成物が容器詰め飲料又は容器詰めゼリー飲料である、［５］～［７］のいずれかに記載の方法。
［９］酸性組成物中における葉酸、ビタミンＢ１２及びビオチンからなる群から選択される１種以上の安定性を向上させる方法であって、前記組成物中に含まれるエタノールの量を０．１重量％未満とすることを含む、方法。
［１０］前記組成物中に含まれるエタノール、グリセリン、メタノール、酢酸、ギ酸及びブチルアミンの量を合計で０．１重量％未満とすることを含む、［９］に記載の方法。
［１１］前記組成物中に含まれるプロトン性有機溶媒の量を合計で０．１重量％未満とすることを含む、［１０］に記載の方法。
［１２］前記組成物が容器詰め飲料又は容器詰めゼリー飲料である、［９］～［１１］のいずれかに記載の方法。 The present invention is based on these findings and includes the following inventions.
[1] An acidic composition containing one or more selected from the group consisting of folic acid, vitamin B 12 and biotin, characterized in that the content of ethanol is less than 0.1% by weight object.
[2] The composition according to [1], wherein the total content of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine is less than 0.1% by weight in total.
[3] The composition according to [2], wherein the content of the protic organic solvent is less than 0.1% by weight in total.
[4] The composition according to any one of [1] to [3], which is a container-packed beverage or a container-packed jelly beverage.
[5] A method for producing an acidic composition containing one or more selected from the group consisting of folic acid, vitamin B 12 and biotin, which contains raw materials such that the amount of ethanol is less than 0.1% by weight How to do that.
[6] The method according to [5], which comprises blending the raw materials so that the total amount of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine is less than 0.1% by weight.
[7] The method according to [6], which comprises blending the raw materials so that the total amount of protic organic solvent is less than 0.1% by weight.
[8] The method according to any one of [5] to [7], wherein the composition is a container-packed beverage or a container-packed jelly beverage.
[9] A method for improving the stability of one or more selected from the group consisting of folic acid, vitamin B 12 and biotin in an acidic composition, comprising 0.1% of the amount of ethanol contained in the composition A method comprising including less than weight percent.
[10] The method according to [9], comprising bringing the amounts of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine in total into the composition below 0.1% by weight in total.
[11] The method according to [10], wherein the total amount of the protic organic solvent contained in the composition is less than 0.1% by weight.
[12] The method according to any one of [9] to [11], wherein the composition is a container-packed beverage or a container-packed jelly beverage.
　本明細書は本願の優先権の基礎となる日本国特許出願番号２０１７-２４７３３６号及び日本国特許出願番号２０１７-２４７３４０号の開示内容を包含する。 The present specification includes the disclosure contents of Japanese Patent Application No. 2017-247336 and Japanese Patent Application No. 2017-247340 based on which the priority of the present application is based.
　本発明によれば、葉酸、ビタミンＢ１２及びビオチンからなる群から選択される１種以上のビタミンＢ群化合物の分解速度が低減されている、及び／又は前記ビタミンＢ群化合物の安定性が優れた、前記ビタミンＢ群化合物を含有する酸性組成物を提供することができる。本発明によれば、保存安定性に優れ、前記ビタミンＢ群化合物を効率的に摂取することが可能な、前記ビタミンＢ群化合物を含有する酸性組成物を提供することができる。 According to the present invention, the decomposition rate of one or more vitamin B group compounds selected from the group consisting of folic acid, vitamin B 12 and biotin is reduced, and / or the stability of the vitamin B group compounds is excellent. Moreover, the acidic composition containing said vitamin-B group compound can be provided. According to the present invention, it is possible to provide an acidic composition containing the above-mentioned vitamin B group compound which is excellent in storage stability and capable of efficiently ingesting the above-mentioned vitamin B group compound.
　本発明は、葉酸、ビタミンＢ１２及びビオチンからなる群から選択される１種以上のビタミンＢ群化合物を含有し、かつエタノールの含有量が低減されていることを特徴とする酸性組成物に関する。 The present invention relates to an acidic composition comprising one or more vitamin B-group compounds selected from the group consisting of folic acid, vitamin B 12 and biotin, and having a reduced content of ethanol.
　本明細書中では、「ビタミンＢ群化合物」又は「前記ビタミンＢ群化合物」という用語は、特に限定のない限り、「葉酸、ビタミンＢ１２及びビオチンからなる群から選択される１種以上のビタミンＢ群化合物」を指す。 In the present specification, the term "vitamin B compound" or "the aforementioned vitamin B compound" is, unless otherwise specified, one or more vitamins selected from the group consisting of folic acid, vitamin B 12 and biotin. "Group B compound".
　本発明の一実施形態では、葉酸、ビタミンＢ１２及びビオチンからなる群から選択される１種以上のビタミンＢ群化合物は、葉酸である。 In one embodiment of the present invention, the one or more vitamin B group compounds selected from the group consisting of folic acid, vitamin B 12 and biotin is folic acid.
　本発明の一実施形態では、葉酸、ビタミンＢ１２及びビオチンからなる群から選択される１種以上のビタミンＢ群化合物は、ビタミンＢ１２である。 In one embodiment of the present invention, folic acid, one or more vitamin B group compound is selected from the group consisting of vitamin B 12 and biotin is vitamin B 12.
　本発明の一実施形態では、葉酸、ビタミンＢ１２及びビオチンからなる群から選択される１種以上のビタミンＢ群化合物は、ビタミンＢ１２である。 In one embodiment of the present invention, folic acid, one or more vitamin B group compound is selected from the group consisting of vitamin B 12 and biotin is vitamin B 12.
　本発明の組成物の一実施形態は、葉酸を含有し、かつエタノールの含有量が低減されていることを特徴とする酸性組成物である。 One embodiment of the composition of the present invention is an acidic composition characterized by containing folic acid and having a reduced content of ethanol.
　本発明の組成物の一実施形態は、ビタミンＢ１２を含有し、かつエタノールの含有量が低減されていることを特徴とする酸性組成物である。 One embodiment of the compositions of the present invention is an acidic composition, characterized in that contain vitamin B 12, and the content of ethanol is reduced.
　本発明の組成物の一実施形態は、ビオチンを含有し、かつエタノールの含有量が低減されていることを特徴とする酸性組成物である。 One embodiment of the composition of the present invention is an acidic composition characterized by containing biotin and having a reduced content of ethanol.
　本発明において、「葉酸」とは、ビタミンＢ複合体の水溶性ビタミンの一つであり、プテロイルモノグルタミン酸と称される下記構造式で表される化合物、 In the present invention, “folic acid” is one of the water-soluble vitamins of the vitamin B complex, and is a compound represented by the following structural formula called pteroyl monoglutamic acid,
Figure JPOXMLDOC01-appb-C000001
Figure JPOXMLDOC01-appb-C000001
あるいはその誘導体又は医薬品や飲食品において許容可能なその塩を意味する。誘導体としては例えば、複数のグルタミン酸が結合したポリグルタミン酸型等が挙げられるが、これらに限定はされない。 Alternatively, it means a derivative thereof or a salt thereof which is acceptable in medicines, food and drink. Examples of the derivative include, but are not limited to, a polyglutamic acid type in which a plurality of glutamic acids are bound, and the like.
　葉酸は食物から抽出又は精製されたものであってもよいし、化学的に合成されたものであってもよい。葉酸を含有する食物としては、特に限定はされないが、アスパラガス、ブロッコリー、ホウレンソウ、エダマメ、ソラマメ、トウモロコシ、メキャベツ、ケール、クキニンニク、シュンギク等の野菜や、ライチ、イチゴ、マンゴー、アボガド、ドリアン等の果物や、トリ、ウシ、ブタのレバー等の肉類を挙げることができる。また、葉酸の合成方法は公知の手法（第８版食品添加物公定書解説書、Ｄ－１６５５～Ｄ－１６６０頁、株式会社廣川書店、平成１９年１２月１０日発行）に基づいて行うことができ、例えば、２，４，５－トリアミノ－６－ヒドロキシピリミジンとバラアミノベンゾイルグルタミン酸の等モル水溶液をｐＨ４に保ちながら、α，β－ジブロモプロピオンアルデヒドのエタノール溶液を加えて縮合させ、これをｐＨ９以上の水溶液に溶かした後、ｐＨ７に調整して不溶物を除去することによって精製された葉酸を得ることができる（本手法に限定はされない）。 Folic acid may be extracted or purified from food, or may be chemically synthesized. The food containing folic acid is not particularly limited, but vegetables such as asparagus, broccoli, spinach, green soybeans, broad bean, corn, cabbage, kale, quill garlic, sun gins, etc., litchi, strawberry, mango, avocado, durian, etc. There can be mentioned fruits and meats such as avian, bovine and porcine liver. In addition, the synthesis method of folic acid is to be carried out based on a known method (eighth edition food additive standard document, pages D-1655 to D-1660, Kamogawa Shoten Co., Ltd., published on December 10, 2007). For example, while maintaining an equimolar aqueous solution of 2,4,5-triamino-6-hydroxypyrimidine and roseaminobenzoyl glutamic acid at pH 4, an ethanol solution of .alpha.,. Beta.-dibromopropionaldehyde is added and condensed to give After dissolving in an aqueous solution of pH 9 or more, it is adjusted to pH 7 to remove insolubles, whereby purified folic acid can be obtained (the invention is not limited thereto).
　本発明の組成物は、一実施形態において、葉酸を含む。葉酸を含む実施形態の組成物には葉酸を、０．１ｐｐｍ～１０ｐｐｍ、好ましくは１ｐｐｍ～１０ｐｐｍ、より好ましくは、１ｐｐｍ～５ｐｐｍの範囲より選択される量にて適宜含めることができる。例えば、本実施形態の組成物には一回の経口摂取量当たり、葉酸を１００μｇ以上、１５０μｇ以上、２００μｇ以上、２４０μｇ以上、２５０μｇ以上、３００μｇ以上、３５０μｇ以上、４００μｇ以上、４５０μｇ以上、５００μｇ以上、５５０μｇ以上の範囲で適宜含めることができる。例えば、厚生労働省が公表する「日本人の食事摂取基準（２０１５年版）」にて推奨される葉酸の摂取量（日）が含まれる範囲が好ましい。一回の経口摂取量当たりに含まれる葉酸の量の上限は特に限定されず、例えば、１０００μｇ以下、９００μｇ以下、８００μｇ以下、７００μｇ以下、６００μｇ以下の範囲より適宜決定することができる。 The composition of the present invention, in one embodiment, comprises folic acid. Folic acid can be suitably included in the composition of the embodiment containing folic acid in an amount selected from the range of 0.1 ppm to 10 ppm, preferably 1 ppm to 10 ppm, more preferably 1 ppm to 5 ppm. For example, the composition of the present embodiment has 100 μg or more, 150 μg or more, 200 μg or more, 240 μg or more, 250 μg or more, 300 μg or more, 350 μg or more, 400 μg or more, 450 μg or more, or 500 μg or more of folic acid per single oral intake. It can be suitably contained in the range of 550 μg or more. For example, a range including the intake (day) of folic acid recommended in "Japanese food intake criteria (2015 version)" published by MHLW is preferable. The upper limit of the amount of folic acid contained per single oral intake is not particularly limited, and can be appropriately determined, for example, from the range of 1000 μg or less, 900 μg or less, 800 μg or less, 700 μg or less, 600 μg or less.
　本明細書において「一回の経口摂取量」とは、上記組成物が一度に経口摂取される量、あるいは短い時間間隔（例えば１０分以下、好ましくは５分以下の時間）をおいて連続的に複数回で経口摂取される総量を意味する。当該組成物が液状又は半固形状（ゲル状、ゾル状等）の形態である場合には、例えば５０ｍＬ～５００ｍＬ（典型的には５０ｍＬ、１００ｍＬ、１５０ｍＬ、１８０ｍＬ、２００ｍＬ、２５０ｍＬ、３００ｍＬ、３５０ｍＬ、４００ｍＬ、４５０ｍＬ又は５００ｍＬ）がその量である。 As used herein, “a single oral intake” refers to an amount at which the composition is orally ingested at one time, or continuously at short time intervals (eg, a time of 10 minutes or less, preferably 5 minutes or less). It means the total amount taken orally in several times. When the composition is in the form of liquid or semisolid (gel or sol, etc.), for example, 50 mL to 500 mL (typically 50 mL, 100 mL, 150 mL, 180 mL, 200 mL, 250 mL, 300 mL, 350 mL, 400 mL, 450 mL or 500 mL) is the volume.
　本発明において、「ビタミンＢ１２」とは、ビタミンＢ複合体の水溶性ビタミンの一つであり、コバルトを含むビタミンの総称である。ビタミンＢ１２は、ヒドロキソコバラミン、アデノシルコバラミン、メチルコバラミン、シアノコバラミン、スルフィトコバラミン、或いは、医薬品や飲食品において許容可能なその誘導体又はその塩を、具体的な化合物として包含する。 In the present invention, “vitamin B 12 ” is one of the water-soluble vitamins of the vitamin B complex, and is a generic term for vitamins including cobalt. Vitamin B 12 includes, hydroxocobalamin, adenosyl cobalamin, methylcobalamin, cyanocobalamin, sulfite cobalamin or its derivative or a salt thereof acceptable in the pharmaceutical and food products, as a specific compound.
　ビタミンＢ１２は食物から抽出又は精製されたものであってもよいし、微生物により生産されたものであってもよいし、化学的に合成されたものであってもよい。ビタミンＢ１２を含有する食物としては、特に限定はされないが、牡蠣、しじみ、イクラ、さんま、にしん等の魚介類や、トリ、ウシ、ブタのレバー等の肉類を挙げることができる。 Vitamin B 12 may be extracted or purified from food, may be produced by a microorganism, or may be chemically synthesized. The food containing vitamin B 12 is not particularly limited, but fish such as oyster, shijimi, salmon roe, saury and lice, meat such as avian, bovine and porcine liver can be mentioned.
　ビタミンＢ１２のうちシアノコバラミンは、放線菌（ストレプトマイセス属）又は細菌（アグロバクテリウム属、バシルス属、フラボバクテリウム属、プロピオニバクテリウム属、リゾビウム属）などの培養液より分離して得ることができる。 Cyanocobalamin of vitamin B 12 is Actinomycetes (Streptomyces) or bacteria (genus Agrobacterium, the genus Bacillus, Flavobacterium, the genus Propionibacterium, Rhizobium) may be separated from the culture medium, such as be able to.
　本発明の組成物は、一実施形態において、ビタミンＢ１２を含む。ビタミンＢ１２を含む実施形態の組成物にはビタミンＢ１２を、０．００１ｐｐｍ～５ｐｐｍ、好ましくは０．００５ｐｐｍ～０．５ｐｐｍ、より好ましくは、０．０１ｐｐｍ～０．０５ｐｐｍの範囲より選択される量にて適宜含めることができる。例えば、本実施形態の組成物には一回の経口摂取量当たり、ビタミンＢ１２を０．９μｇ以上、１．０μｇ以上、１．２μｇ以上、１．５μｇ以上、１．８μｇ以上、２．０μｇ以上、２．１μｇ以上、２．２μｇ以上、２．３μｇ以上、２．４μｇ以上、２．５μｇ以上、３．０μｇ以上、３．２μｇ以上の範囲で適宜含めることができる。例えば、厚生労働省が公表する「日本人の食事摂取基準（２０１５年版）」にて推奨されるビタミンＢ１２の摂取量（日）が含まれる範囲が好ましい。一回の経口摂取量当たりに含まれるビタミンＢ１２の量の上限は特に限定されず、例えば、１０μｇ以下、９μｇ以下、８μｇ以下、７μｇ以下、５μｇ以下、４μｇ以下の範囲より適宜決定することができる。 The compositions of the present invention, in one embodiment, vitamin B 12. The composition of the embodiment containing vitamin B 12 is selected from the range of 0.001 ppm to 5 ppm, preferably 0.005 ppm to 0.5 ppm, more preferably 0.01 ppm to 0.05 ppm of vitamin B 12 It can be included appropriately in the amount. For example, the composition of the present embodiment has 0.9 μg or more, 1.0 μg or more, 1.2 μg or more, 1.5 μg or more, 1.8 μg or more, 2.0 μg or more of vitamin B 12 per single oral intake. As mentioned above, it can be suitably included in the range of 2.1 μg or more, 2.2 μg or more, 2.3 μg or more, 2.4 μg or more, 2.5 μg or more, 3.0 μg or more, 3.2 μg or more. For example, a range including the intake amount (day) of vitamin B 12 recommended by the “Japanese food intake standard (2015 version)” published by MHLW is preferable. The upper limit of the amount of vitamin B 12 contained in a single oral intake is not particularly limited. For example, it may be appropriately determined from the range of 10 μg or less, 9 μg or less, 8 μg or less, 7 μg or less, 5 μg or less, 4 μg or less it can.
　本発明において、「ビオチン」は必須の水溶性ビタミンの一つであり、下記構造式で表される化合物： In the present invention, "biotin" is one of the essential water-soluble vitamins, and is a compound represented by the following structural formula:
Figure JPOXMLDOC01-appb-C000002
Figure JPOXMLDOC01-appb-C000002
或いは、医薬品や飲食品において許容可能なその誘導体又はその塩を意味する。 Alternatively, it means an acceptable derivative thereof or a salt thereof in medicines and foods and beverages.
　ビオチンは食物から抽出又は精製されたものであってもよいし、化学的に合成されたものであってもよい。ビオチンを含有する食物としては、特に限定はされないが、ウシのレバーや卵黄、大豆などの豆・穀類を挙げることができる。 Biotin may be extracted or purified from food, or may be chemically synthesized. The food containing biotin is not particularly limited, but can be bovine liver, egg yolk, beans such as soybeans and grains.
　本発明の組成物は、一実施形態において、ビオチンを含む。ビオチンを含む実施形態の組成物にはビオチンを、０．００１ｐｐｍ～１０ｐｐｍ、好ましくは０．０１ｐｐｍ～１ｐｐｍ、より好ましくは、０．２ｐｐｍ～０．３ｐｐｍの範囲より選択される量にて適宜含めることができる。例えば、本発明の組成物には一回の経口摂取量当たり、ビオチンを１０μｇ以上、１５μｇ以上、２０μｇ以上、２５μｇ以上、３０μｇ以上、３５μｇ以上、４０μｇ以上、４５μｇ以上、５０μｇ以上、６０μｇ以上、７０μｇ以上、１００μｇ以上の範囲で適宜含めることができる。例えば、厚生労働省が公表する「日本人の食事摂取基準（２０１５年版）」にて推奨されるビオチンの摂取量（日）が含まれる範囲が好ましい。一回の経口摂取量当たりに含まれるビオチンの量の上限は特に限定されず、例えば、１０００μｇ以下、５００μｇ以下、４００μｇ以下、３００μｇ以下、２００μｇ以下、１５０μｇ以下の範囲より適宜決定することができる。 The composition of the present invention, in one embodiment, comprises biotin. The composition of the embodiment containing biotin suitably contains biotin in an amount selected from the range of 0.001 ppm to 10 ppm, preferably 0.01 ppm to 1 ppm, more preferably 0.2 ppm to 0.3 ppm. Can. For example, the composition of the present invention contains 10 μg or more, 15 μg or more, 20 μg or more, 25 μg or more, 30 μg or more, 35 μg or more, 40 μg or more, 45 μg or more, 50 μg or more, 60 μg or more of 70 μg of biotin per single oral intake. As mentioned above, it can be suitably included in the range of 100 μg or more. For example, a range that includes the intake amount (day) of biotin recommended in “Japanese food intake criteria (2015 version)” published by the Ministry of Health, Labor and Welfare is preferable. The upper limit of the amount of biotin contained per single oral intake is not particularly limited, and can be appropriately determined, for example, from 1000 μg or less, 500 μg or less, 400 μg or less, 300 μg or less, 200 μg or less, 150 μg or less.
　本発明において、「プロトン性有機溶媒」とは、自分自身で解離してプロトンを生じる有機溶媒を意味し、電気陰性度の大きな原子、すなわち、窒素原子や酸素原子に結合した水素原子を有するものを意味する。このようなプロトン性有機溶媒としては、例えば、低級アルコール（エタノール、メタノール）、グリセリン、酢酸、ギ酸、ブチルアミン等が挙げられるが、これらに限定はされない。 In the present invention, "protonic organic solvent" means an organic solvent which dissociates by itself to generate a proton, and has an atom of high electronegativity, that is, a hydrogen atom bonded to a nitrogen atom or an oxygen atom Means Examples of such protic organic solvents include, but are not limited to, lower alcohols (ethanol, methanol), glycerin, acetic acid, formic acid, butylamine and the like.
　下記実施例にて詳述されるとおり、エタノールは、酸性組成物中にて前記ビタミンＢ群化合物の分解速度を増大させる効果を有する。したがって、酸性組成物中に含まれるエタノールの量を低減することによって、酸性組成物中における前記ビタミンＢ群化合物の分解速度を低減することができ、酸性組成物中における前記ビタミンＢ群化合物の保存安定性を高めることができる。エタノールだけでなく、エタノールと同様にプロトン性有機溶媒であるグリセリン、メタノール、酢酸、ギ酸及びブチルアミンもまた、前記ビタミンＢ群化合物の分解速度を増大させる効果を有するため、好ましくは、酸性組成物中に含まれるエタノール、グリセリン、メタノール、酢酸、ギ酸及びブチルアミンの合計量を低減することによって、酸性組成物中における前記ビタミンＢ群化合物の分解速度を低減することができ、酸性組成物中における前記ビタミンＢ群化合物の保存安定性を高めることができる。特に好ましくは、酸性組成物中に含まれるプロトン性有機溶媒（エタノール、グリセリン、メタノール、酢酸、ギ酸、ブチルアミン等を含む）の合計量を低減することによって、酸性組成物中における前記ビタミンＢ群化合物の分解速度を低減することができ、酸性組成物中における前記ビタミンＢ群化合物の保存安定性を高めることができる。 As detailed in the examples below, ethanol has the effect of increasing the rate of degradation of the Group B vitamin compound in the acidic composition. Therefore, by reducing the amount of ethanol contained in the acidic composition, the degradation rate of the vitamin B group compound in the acidic composition can be reduced, and the preservation of the vitamin B group compound in the acidic composition It can improve stability. Not only ethanol, but also the protic organic solvents glycerin, methanol, acetic acid, formic acid and butylamine as well as ethanol have an effect of increasing the decomposition rate of the vitamin B group compound, so preferably in an acidic composition By reducing the total amount of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine contained therein, it is possible to reduce the decomposition rate of the vitamin B group compound in the acidic composition, The storage stability of the group B compound can be enhanced. Particularly preferably, the vitamin B group compound in the acidic composition is reduced by reducing the total amount of protic organic solvents (including ethanol, glycerin, methanol, acetic acid, formic acid, butylamine and the like) contained in the acidic composition. The decomposition rate of the compound can be reduced, and the storage stability of the group B vitamin compound in the acidic composition can be enhanced.
　本発明の組成物に含まれるエタノールの量は、前記ビタミンＢ群化合物の分解速度を低減し、及び／又は、保存安定性を高めるために、可能な限り低減させることが好ましく、組成物に含まれるエタノールの含有量を低減させるほど、組成物における前記ビタミンＢ群化合物の保存安定性を高めることができる。例えば、前記ビタミンＢ群化合物を含有する従来の酸性組成物よりも、含まれるエタノールの量を低減することによって、従来の酸性組成物と比べて、前記ビタミンＢ群化合物の分解速度が低減し、及び／又は、保存安定性の高い組成物を得ることができる。したがって、本発明の組成物に含まれるエタノールの量は、前記ビタミンＢ群化合物を含有する従来の酸性組成物におけるエタノールの量と比べて少ない量であればよく、特に限定されるものではないが、具体的には０．１重量％未満、例えば、０．０９重量％未満、０．０８重量％未満、０．０７重量％未満、又は０．０６重量％未満の範囲とすることができる。特に好ましくは、０．０５重量％以下、０．０４重量％以下、０．０３重量％以下、０．０２重量％以下、又は０．０１重量％以下の範囲とすることができる。 The amount of ethanol contained in the composition of the present invention is preferably reduced as much as possible in order to reduce the decomposition rate of the vitamin B group compound and / or enhance storage stability, and is included in the composition. As the content of ethanol is reduced, the storage stability of the vitamin B group compound in the composition can be enhanced. For example, by reducing the amount of ethanol contained relative to the conventional acidic composition containing the vitamin B group compound, the decomposition rate of the vitamin B group compound is reduced as compared to the conventional acidic composition, And / or a composition having high storage stability can be obtained. Therefore, the amount of ethanol contained in the composition of the present invention may be small as compared to the amount of ethanol in the conventional acidic composition containing the vitamin B group compound, and is not particularly limited. Specifically, it may be in the range of less than 0.1 wt%, for example, less than 0.09 wt%, less than 0.08 wt%, less than 0.07 wt%, or less than 0.06 wt%. Particularly preferably, it can be in the range of 0.05 wt% or less, 0.04 wt% or less, 0.03 wt% or less, 0.02 wt% or less, or 0.01 wt% or less.
　本発明の組成物における、エタノール、グリセリン、メタノール、酢酸、ギ酸及びブチルアミンの合計量は、前記ビタミンＢ群化合物の分解速度を更に低減し、及び／又は、保存安定性を更に高めるために、可能な限り低減させることが好ましい。本発明の組成物中のエタノール、グリセリン、メタノール、酢酸、ギ酸及びブチルアミンの合計量は、前記ビタミンＢ群化合物を含有する従来の酸性組成物における前記合計量と比べて少ない量であればよく、特に限定されるものではないが、具体的には０．１重量％未満、例えば、０．０９重量％未満、０．０８重量％未満、０．０７重量％未満、又は０．０６重量％未満の範囲とすることができる。特に好ましくは、０．０５重量％以下、０．０４重量％以下、０．０３重量％以下、０．０２重量％以下、又は０．０１重量％以下の範囲とすることができる。 The total amount of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine in the composition of the present invention is possible to further reduce the decomposition rate of the group B compound and / or to further enhance the storage stability. It is preferable to reduce as much as possible. The total amount of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine in the composition of the present invention may be a small amount as compared to the total amount in the conventional acidic composition containing the vitamin B group compound, Although not particularly limited, specifically, it is less than 0.1 wt%, for example, less than 0.09 wt%, less than 0.08 wt%, less than 0.07 wt%, or less than 0.06 wt% It can be in the range of Particularly preferably, it can be in the range of 0.05 wt% or less, 0.04 wt% or less, 0.03 wt% or less, 0.02 wt% or less, or 0.01 wt% or less.
　本発明の組成物における、エタノール、グリセリン、メタノール、酢酸、ギ酸、ブチルアミン等を含むプロトン性有機溶媒の合計量は、前記ビタミンＢ群化合物の分解速度を更に低減し、及び／又は、保存安定性を更に高めるために、可能な限り低減させることが好ましい。本発明の組成物中のプロトン性有機溶媒の合計量は、前記ビタミンＢ群化合物を含有する従来の酸性組成物における前記合計量と比べて少ない量であればよく、特に限定されるものではないが、具体的には０．１重量％未満、例えば、０．０９重量％未満、０．０８重量％未満、０．０７重量％未満、又は０．０６重量％未満の範囲とすることができる。特に好ましくは、０．０５重量％以下、０．０４重量％以下、０．０３重量％以下、０．０２重量％以下、又は０．０１重量％以下の範囲とすることができる。 The total amount of the protic organic solvent in the composition of the present invention including ethanol, glycerin, methanol, acetic acid, formic acid, butylamine and the like further reduces the decomposition rate of the vitamin B group compound and / or storage stability It is preferable to reduce as much as possible to further enhance the The total amount of the protic organic solvent in the composition of the present invention may be a small amount as compared to the total amount in the conventional acidic composition containing the vitamin B group compound, and is not particularly limited. In particular, it may be in the range of less than 0.1% by weight, such as less than 0.09% by weight, less than 0.08% by weight, less than 0.07% by weight, or less than 0.06% by weight. . Particularly preferably, it can be in the range of 0.05 wt% or less, 0.04 wt% or less, 0.03 wt% or less, 0.02 wt% or less, or 0.01 wt% or less.
　本発明における「エタノール」、「エタノール、グリセリン、メタノール、酢酸、ギ酸及びブチルアミン」並びに「プロトン性有機溶媒」という用語は、それぞれ、本発明の酸性組成物の製造過程において配合されるものだけでなく、当該組成物の製造に用いられる原材料の製造過程において配合される／混入するものも包含する。例えば、今日、ほとんど全ての種類の香料製剤にはエタノールが含有される（植松ら、食衛誌、Vol.38,No.6,pp.452-459, December, 1997）。しかしながら、市販の香料製剤については、最終製品に配合した希釈剤は表示されるが、香料の抽出に用いた溶剤の場合には表示されない場合があり、また、香料製剤を調合する際に多種類の香料を混合することから、混合前の香料に含有されていた溶剤は表示されない場合がある。このため、香料製剤についてエタノールを含む旨の表示がない場合であっても、実際には含まれる場合があり、このような香料製剤を本発明の組成物に配合した場合には、組成物中のエタノールの含量を増大させ、前記ビタミンＢ群化合物の分解速度を増大させ得る。 The terms "ethanol", "ethanol, glycerin, methanol, acetic acid, formic acid and butylamine" and "protic organic solvent" in the present invention are not only those which are compounded in the process of producing the acidic composition of the present invention, respectively. Also included are those which are incorporated / contaminated in the process of producing the raw materials used for producing the composition. For example, ethanol is contained in almost all types of perfume formulations today (Uematsu et al., Food Safety Journal, Vol. 38, No. 6, pp. 452-459, December, 1997). However, for commercially available perfume formulations, the diluent blended in the final product is displayed but may not be displayed in the case of the solvent used for extracting the perfume, and there are also many types of compounds when formulating the perfume formulation. The solvent contained in the fragrance before mixing may not be displayed because the fragrance is mixed. For this reason, even if there is no indication that ethanol is included in the perfume formulation, it may actually be included, and when such a perfume formulation is blended in the composition of the present invention, it may be in the composition. Can increase the ethanol content of to increase the degradation rate of the group B compound.
　なお、本発明の組成物中の「エタノール」、「エタノール、グリセリン、メタノール、酢酸、ギ酸及びブチルアミン」並びに「プロトン性有機溶媒」の量は、それぞれ、従来公知の一般的な手法により測定することが可能である。例えば、組成物中の各溶媒成分の含有量は、当該組成物を無水硫酸ナトリウム及びアセトニトリルと混合し、これをろ過し、得られたろ液をアセトニトリルに溶解した液を分析サンプルとして、ガスクロマトグラフィーに付すことにより求めることができる（一色賢司、食衛誌．Ｖｏｌ．２６，Ｎｏ．１，ｐｐ.３９－４５，１９８５）。 The amounts of “ethanol”, “ethanol, glycerin, methanol, acetic acid, formic acid and butylamine” and “protic organic solvent” in the composition of the present invention are each measured by a commonly known conventional method. Is possible. For example, the content of each solvent component in the composition is obtained by mixing the composition with anhydrous sodium sulfate and acetonitrile, filtering it, and using the solution obtained by dissolving the obtained filtrate in acetonitrile as an analysis sample, gas chromatography It can be determined by adding it to the index (Kenji Isshiki, Food Safety. Vol. 26, No. 1, pp. 39-45, 1985).
　本発明において、「酸性組成物」とは、ｐＨ値が４．５以下である組成物を意味し、例えば、ｐＨ４．５未満、ｐＨ４．４未満、ｐＨ４．３未満、ｐＨ４．２未満、ｐＨ４．１未満、ｐＨ４．０未満、ｐＨ３．９未満、ｐＨ３．８未満、ｐＨ３．７未満、ｐＨ３．６未満、ｐＨ３．５未満、ｐＨ３．４未満、又は、ｐＨ３．３未満とすることができる。ｐＨ値の下限は特に限定されず、酸性組成物の形態に応じて適宜決定することが可能であり、例えば、ｐＨ２．５以上、ｐＨ２．６以上、ｐＨ２．７以上、ｐＨ２．８以上、ｐＨ２．９以上、ｐＨ３．０以上、ｐＨ３．１以上、又は、ｐＨ３．２以上とすることができる。 In the present invention, the "acidic composition" means a composition having a pH value of 4.5 or less, for example, less than 4.5, less than 4.4, less than 4.3, less than 4.2, pH 4 Less than 1, less than pH 4.0, less than pH 3.9, less than pH 3.8, less than pH 3.7, less than pH 3.6, less than pH 3.5, less than pH 3.4, or less than pH 3.3 . The lower limit of the pH value is not particularly limited, and can be appropriately determined according to the form of the acidic composition. For example, pH 2.5 or more, pH 2.6 or more, pH 2.7 or more, pH 2.8 or more, pH 2 .9 or more, pH 3.0 or more, pH 3.1 or more, or pH 3.2 or more.
　本発明の酸性組成物が清涼飲料水の形態である場合には、当該ｐＨ値はｐＨ４．０未満とすることが好ましい。食品衛生法の食品別規格基準によれば、清涼飲料水の殺菌・除菌の方法はｐＨ４．０を境に大きく異なっており、ｐＨ４．０未満のものの殺菌は、中心部温度を６５℃にて１０分間加熱することが求められるのに対して、ｐＨ４．０以上のものの殺菌は、中心部温度を８５℃にて３０分間加熱することが求められる。故に、ｐＨ値の上限をｐＨ４．０未満とすることによって、殺菌工程による負荷を小さくし、殺菌工程における前記ビタミンＢ群化合物の分解を小さくすることができ、好ましい。なお、本明細書において、ｐＨ値は品温２０℃で測定された値を指す。 When the acidic composition of the present invention is in the form of a soft drink, the pH value is preferably less than pH 4.0. According to the food-specific standards of the Food Sanitation Law, the methods for sterilization and sterilization of soft drinks are largely different at pH 4.0, and those below pH 4.0 have a core temperature of 65 ° C. While it is required to heat for 10 minutes, sterilization of pH 4.0 or more is required to heat the core temperature at 85 ° C. for 30 minutes. Therefore, by setting the upper limit of the pH value to less than pH 4.0, the load by the sterilization step can be reduced, and the decomposition of the vitamin B group compound in the sterilization step can be reduced, which is preferable. In addition, in this specification, pH value points out the value measured by 20 degreeC of substance temperature.
　本発明の酸性組成物のｐＨ値は、加えられる酸味料の量を適宜調節することによって調節することができる。酸味料としては医薬や飲食品の製造に一般的に利用されるものが挙げられ、例えばクエン酸、リンゴ酸、グルコン酸、酒石酸、乳酸、コハク酸、又はこれらの塩などがあり、これらのうちの１種又は２種以上の混合物を加えることができる。 The pH value of the acidic composition of the present invention can be adjusted by appropriately adjusting the amount of acidulant added. Examples of the acidulant include those generally used in the manufacture of medicines and foods and drinks, and examples thereof include citric acid, malic acid, gluconic acid, tartaric acid, lactic acid, succinic acid, and salts thereof. Or mixtures of two or more can be added.
　本発明の酸性組成物には、前記ビタミンＢ群化合物に加えて、医薬又は飲食品として許容可能な賦形剤、崩壊剤、滑沢剤、結合剤、酸化防止剤、着色剤、凝集防止剤、吸収促進剤、溶剤、溶解補助剤、等張化剤、安定化剤、矯味矯臭剤、ｐＨ調整剤、香料製剤、甘味料、増粘剤、防腐剤、ビタミン類、寒天等のその他の原材料を、当該組成物において所望される形態に応じて適宜選択、配合することができる。ただし、これらの成分は、エタノールを含まない、又はエタノールの含量が低いものを利用することが好ましく、エタノール、グリセリン、メタノール、酢酸、ギ酸及びブチルアミンを含まない、又はそれらの合計含量が低いものを利用することがより好ましく、プロトン性有機溶媒（エタノール、グリセリン、メタノール、酢酸、ギ酸、ブチルアミン等を含む）を含まない、又はプロトン性有機溶媒の合計含量が低いものを利用することが特に好ましい。例えば、上記のとおり、今日、ほとんど全ての種類の香料製剤にはエタノールが溶媒として含有される。本発明においては、このような香料製剤に代えて、溶媒としてエタノールではなく、中鎖脂肪酸及び／又は乳化剤から選択される一又は複数を利用する香料製剤を含めることができる。ここで特に限定されるものではないが、中鎖脂肪酸としては、Ｃ８，Ｃ１０，Ｃ１２トリグリセライド等を利用することが可能であり、乳化剤としては、グリセリン脂肪酸エステル、ソルビタン脂肪酸エステル、プロピレングリコール脂肪酸エステル、ショ糖脂肪酸エステル等を利用することができる。 In the acidic composition of the present invention, in addition to the vitamin B group compound, a pharmaceutically or food-acceptable excipient, a disintegrant, a lubricant, a binder, an antioxidant, a coloring agent, an aggregation inhibitor Absorption accelerators, solvents, solubilizers, tonicity agents, stabilizers, flavoring agents, pH adjusters, flavor preparations, sweeteners, thickeners, preservatives, vitamins, other raw materials such as agar Can be appropriately selected and blended according to the form desired in the composition. However, it is preferable that these components do not contain ethanol or that the content of ethanol is low, and do not contain ethanol, glycerin, methanol, acetic acid, formic acid and butylamine, or that their total content is low. It is more preferable to use, and it is particularly preferable to use one which does not contain a protic organic solvent (including ethanol, glycerin, methanol, acetic acid, formic acid, butylamine and the like) or has a low total content of protic organic solvents. For example, as noted above, today, almost all types of perfume formulations contain ethanol as a solvent. In the present invention, in place of such a perfume preparation, a perfume preparation that uses one or more selected from medium-chain fatty acids and / or emulsifiers can be included as a solvent instead of ethanol. Here, C8, C10, C12 triglyceride and the like can be used as the medium chain fatty acid, although not particularly limited, and as the emulsifier, glycerin fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, Sucrose fatty acid ester etc. can be utilized.
　本発明の酸性組成物は、医薬品（医薬部外品を含む）又は飲食品の形態で提供することができる。これらの形態は、液状組成物又は半固形状組成物（ゲル状、ゾル状等）等の形態とすることができ、前記ビタミンＢ群化合物に加えて、上記その他の原材料をその剤形に応じて、適宜配合し、常法に従って調製することができる。 The acidic composition of the present invention can be provided in the form of a pharmaceutical (including quasi drugs) or food and drink. These forms may be in the form of liquid compositions or semisolid compositions (gel-like, sol-like, etc.), and the above-mentioned other raw materials may be added to the vitamin B-group compound according to the dosage form thereof. It can be appropriately blended and prepared according to a conventional method.
　例えば、本発明の酸性組成物は、容器詰め飲料とすることができる。本発明の酸性組成物（液状組成物）を収容するための容器は、飲料用容器として使用される容器を適宜用いることができ、限定されないが、ポリエチレンテレフタレート（ＰＥＴ）製容器、所謂ＰＥＴボトルや、金属缶容器等が挙げられる。容器の形態は特に限定されない。また、容器の容量は特に限定されないが、例えば５０～５００ｍＬ（典型的には５０ｍＬ、１００ｍＬ、１５０ｍＬ、１８０ｍＬ、２００ｍＬ、２５０ｍＬ、３００ｍＬ、３５０ｍＬ、４００ｍＬ、４５０ｍＬ又は５００ｍＬ）、好ましくは１００～２００ｍＬとすることができる。 For example, the acidic composition of the present invention can be a container-packed beverage. As a container for containing the acidic composition (liquid composition) of the present invention, a container used as a container for beverages can be suitably used, and is not limited, but a container made of polyethylene terephthalate (PET), a so-called PET bottle, And metal can containers. The form of the container is not particularly limited. Also, the volume of the container is not particularly limited, but for example, 50 to 500 mL (typically, 50 to 100 mL, 150 to 180 mL, 200 to 250 mL, 300 to 350, 400 to 450 or 500 mL), preferably 100 to 200 be able to.
　あるいは、本発明の酸性組成物は、容器詰めゼリー飲料とすることができる。本発明の酸性組成物（半固形状（ゲル状、ゾル状等）組成物）を収容するための容器は、ゼリー飲料用容器として使用される容器を適宜用いることができ、限定されないが、樹脂フィルム、及び／又は、金属フィルム製容器、パウチ容器等が挙げられる。また、容器の容量は特に限定されないが、例えば５０ｍＬ～２００ｍＬ（典型的には５０ｍＬ、１００ｍＬ、１５０ｍＬ、１８０ｍＬ、２００ｍＬ）とすることができる。 Alternatively, the acidic composition of the present invention can be a container-packed jelly beverage. The container for containing the acidic composition (semi-solid (gel-like, sol-like, etc.) composition) of the present invention may be a container used as a container for jelly drinks, as appropriate, without limitation. A film and / or a container made of a metal film, a pouch container, etc. may be mentioned. Also, the volume of the container is not particularly limited, but can be, for example, 50 mL to 200 mL (typically, 50 mL, 100 mL, 150 mL, 180 mL, 200 mL).
　本発明の酸性組成物は、食物から抽出もしくは精製された前記ビタミンＢ群化合物、又は、化学的に合成された前記ビタミンＢ群化合物、酸味料、必要に応じて上述のようなその他の原材料、並びに残部として水を混合し、エタノールの含有量が前記ビタミンＢ群化合物を含有する従来の酸性組成物におけるエタノールの含有量と比べて少ない量、具体的には０．１重量％未満、例えば、０．０９重量％未満、０．０８重量％未満、０．０７重量％未満、又は０．０６重量％未満の範囲、好ましくは、０．０５重量％以下、０．０４重量％以下、０．０３重量％以下、０．０２重量％以下、又は０．０１重量％以下の範囲となるようにして製造することができる。本発明のより好ましい実施形態に係る酸性組成物は、食物から抽出もしくは精製された前記ビタミンＢ群化合物、又は、化学的に合成された前記ビタミンＢ群化合物、酸味料、必要に応じて上述のようなその他の原材料、並びに残部として水を混合し、エタノール、グリセリン、メタノール、酢酸、ギ酸及びブチルアミンの合計の含有量が前記ビタミンＢ群化合物を含有する従来の酸性組成物におけるエタノールの含有量と比べて少ない量、具体的には０．１重量％未満、例えば、０．０９重量％未満、０．０８重量％未満、０．０７重量％未満、又は０．０６重量％未満の範囲、好ましくは、０．０５重量％以下、０．０４重量％以下、０．０３重量％以下、０．０２重量％以下、又は０．０１重量％以下の範囲となるようにして製造することができる。本発明の特に好ましい実施形態に係る酸性組成物は、食物から抽出もしくは精製された前記ビタミンＢ群化合物、又は、化学的に合成された前記ビタミンＢ群化合物、酸味料、必要に応じて上述のようなその他の原材料、並びに残部として水を混合し、プロトン性有機溶媒の合計の含有量が前記ビタミンＢ群化合物を含有する従来の酸性組成物におけるプロトン性有機溶媒の合計の含有量と比べて少ない量、具体的には０．１重量％未満、例えば、０．０９重量％未満、０．０８重量％未満、０．０７重量％未満、又は０．０６重量％未満の範囲、好ましくは、０．０５重量％以下、０．０４重量％以下、０．０３重量％以下、０．０２重量％以下、又は０．０１重量％以下の範囲となるようにして製造することができる。本発明の酸性組成物の容器への収容、及び殺菌の手段は任意に選択することができる。 The acidic composition of the present invention is the vitamin B group compound extracted or purified from food, or the chemically synthesized vitamin B group compound, acidulant, and other raw materials as described above as needed, As well as mixing the remainder with water, the content of ethanol is small compared to the content of ethanol in the conventional acidic composition containing the vitamin B group compound, specifically less than 0.1% by weight, for example, Less than 0.09% by weight, less than 0.08% by weight, less than 0.07% by weight, or less than 0.06% by weight, preferably 0.05% by weight or less, 0.04% by weight or less, 0. It can manufacture so that it may become the range of 03 weight% or less, 0.02 weight% or less, or 0.01 weight% or less. The acidic composition according to a more preferred embodiment of the present invention is the vitamin B group compound extracted or purified from food, or the chemically synthesized vitamin B group compound, acidulant, as described above, as needed. And other raw materials, and water as the balance, and the total content of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine is the content of ethanol in the conventional acidic composition containing the vitamin B group compound Smaller amounts, specifically less than 0.1% by weight, for example less than 0.09% by weight, less than 0.08% by weight, less than 0.07% by weight, or less than 0.06% by weight, preferably Is manufactured in a range of 0.05 wt% or less, 0.04 wt% or less, 0.03 wt% or less, 0.02 wt% or less, or 0.01 wt% or less Door can be. The acidic composition according to a particularly preferred embodiment of the present invention is the vitamin B group compound extracted or purified from food, or the chemically synthesized vitamin B group compound, acidulant, as described above, as needed. Such other raw materials, as well as water as the balance, the total content of the protic organic solvent is compared with the total content of the protic organic solvent in the conventional acidic composition containing the vitamin B group compound Small amounts, specifically less than 0.1% by weight, for example less than 0.09% by weight, less than 0.08% by weight, less than 0.07% by weight, or less than 0.06% by weight, preferably It can be manufactured to have a range of 0.05 wt% or less, 0.04 wt% or less, 0.03 wt% or less, 0.02 wt% or less, or 0.01 wt% or less. Means for containing the acidic composition of the present invention in a container and means for sterilization can be optionally selected.
　以下に実施例及び試験例を示し、本発明をさらに詳しく説明するが、本発明はこれら実施例に制限されるものではない。 EXAMPLES The present invention will be described in more detail by way of the following Examples and Test Examples, but the present invention is not limited to these Examples.
＜葉酸の安定性の向上＞
Ｉ．材料・測定方法
１．標準原液
　葉酸１００ｍｇを２００ｍＬ褐色ビーカーに精秤し、０．１Ｎ水酸化ナトリウム溶液（和光純薬）を５ｍＬ添加して溶解した。次いで、特級エタノール（和光純薬）１０ｍＬを添加・混和後、イオン交換水１００ｍＬと０．１Ｎ塩酸（和光純薬）にて溶液のｐＨを７．０～８．０に調整した。２００ｍＬ褐色メスフラスコとイオン交換水を用いて所定量に定容し、ＨＰＬＣ測定における検量線作成のための標準原液とした。
２．ＨＰＬＣ測定
　葉酸を含む溶液サンプルは、重量を測定後、１．０Ｎ水酸化ナトリウム溶液（和光純薬）を用いてｐＨ１２．０（ＨＯＲＩＢＡ製ｐＨメーター（Ｆ－７２））に調整した。次いで、１０分間撹拌後（ＡＳ　ＯＮＥ製マグネティックスターラー（ＲＳＨ－１ＡＮ））、１．０Ｎ塩酸（和光純薬）を用いてｐＨ７．０に調整し、ろ過し（ＡＳ　ＯＮＥ製０．４５μｍフィルター（ＳＹ２５ＴＦ））、得られたろ液をＨＰＬＣ測定に付した。 <Improvement of stability of folic acid>
I. Materials and measuring methods Standard stock solution: 100 mg of folic acid was precisely weighed in a 200 mL brown beaker, and dissolved by adding 5 mL of 0.1 N sodium hydroxide solution (Wako Pure Chemical Industries, Ltd.). Next, 10 mL of special grade ethanol (Wako Pure Chemical Industries, Ltd.) was added and mixed, and the pH of the solution was adjusted to 7.0 to 8.0 with 100 mL of ion exchanged water and 0.1 N hydrochloric acid (Wako Pure Chemical Industries, Ltd.). The volume was adjusted to a predetermined amount using a 200 mL brown volumetric flask and ion exchange water, and used as a standard stock solution for preparing a calibration curve in HPLC measurement.
2. HPLC Measurement After measuring the weight, a solution sample containing folic acid was adjusted to pH 12.0 (pH meter (F-72 manufactured by HORIBA)) using a 1.0 N sodium hydroxide solution (Wako Pure Chemical Industries, Ltd.). Then, after stirring for 10 minutes (AS ONE magnetic stirrer (RSH-1AN)), the pH is adjusted to 7.0 using 1.0 N hydrochloric acid (Wako Pure Chemical Industries, Ltd.) and filtered (AS ONE 0.45 μm filter (SY 25 TF) )), The obtained filtrate was subjected to HPLC measurement.
　ＨＰＬＣ測定は、以下の条件にて実施した。 The HPLC measurement was performed under the following conditions.
　装置：Ｗａｔｅｒｓ　ＡＣＱＵＩＴＹ　Ｈ－Ｃｌａｓｓシステム
　カラム：Ｗａｔｅｒｓ　ＸＢｒｉｄｇｅ　Ｃ１８　５μｍ　６×２５０ｍｍ
　温度：５０℃
　流量：１．２ｍｌ／ｍｉｎ
　移動相：１２％メタノール（和光純薬）、０．３％酢酸（和光純薬）、１．０８％オクタスルホン酸Ｎａ溶液（和光純薬）
３．ベース液
　イオン交換水にグラニュー糖２．５重量％、果糖１．２重量％、Ｌ－アスコルビン酸０．８重量％、クエン酸０．２重量％、クエン酸三ナトリウム０．２重量％、及び葉酸０．０００３重量％を添加し、１．０Ｎ塩酸（和光純薬）、及び１．０Ｎ水酸化ナトリウム（和光純薬）を用いて、所定のｐＨに調整し、ベース液とした。
ＩＩ．試験１：エタノール添加の影響（１）
　下記表１に示す組成にしたがって、ベース液、ならびに、エタノール、又は、アセトニトリルを含み、所定のｐＨを有する溶液（実施例１～７、比較例１Ｅ～７Ｅ（エタノール添加）、比較例１Ａ～７Ａ（アセトニトリル添加））をそれぞれ調製した（０日目）。 Device: Waters ACQUITY H-Class System Column: Waters XBridge C18 5μm 6 × 250mm
Temperature: 50 ° C
Flow rate: 1.2 ml / min
Mobile phase: 12% methanol (Wako Pure Chemical Industries, Ltd.), 0.3% acetic acid (Wako Pure Chemical Industries, Ltd.), 1.08% sodium octasulfonate solution (Wako Pure Chemical Industries, Ltd.)
3. Base solution 2.5% by weight of granulated sugar, 1.2% by weight of fructose, 0.8% by weight of L-ascorbic acid, 0.2% by weight of citric acid, 0.2% by weight of trisodium citrate, and ion-exchanged water 0.0003% by weight of folic acid was added, and the pH was adjusted to a predetermined pH using 1.0 N hydrochloric acid (Wako Pure Chemical Industries, Ltd.) and 1.0 N sodium hydroxide (Wako Pure Chemical Industries, Ltd.) to prepare a base solution.
II. Test 1: Effect of ethanol addition (1)
A solution containing a base solution and ethanol or acetonitrile according to the composition shown in the following Table 1 and having a predetermined pH (Examples 1 to 7, Comparative Examples 1E to 7E (ethanol added), Comparative Examples 1A to 7A (Acetonitrile addition) were each prepared (day 0).
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
　各溶液を遮光されたレトルトパウチに１００ｍＬ室温充填し、その後８０℃にて１０分間湯殺菌（ＬＡＵＤＡ製恒温水槽（Ｄ２０ＫＰ））を行った。次いで、各溶液を５０℃で所定の期間保存し（ＡＤＶＡＮＴＥＣ社製恒温庫（ＡＧＸ－３４５））、保存後の各溶液中の葉酸量をＨＰＬＣにより測定した。 Each solution was filled with 100 mL of the solution in a light-shielded retort pouch at room temperature, and then subjected to hot water sterilization (DAUDA thermostatic water tank (D20 KP)) at 80 ° C. for 10 minutes. Next, each solution was stored at 50 ° C. for a predetermined period (ADVANTEC thermostatic chamber (AGX-345)), and the amount of folate in each solution after storage was measured by HPLC.
　保存後の各溶液中の葉酸量の測定結果を下記表２に示す。なお、表中の葉酸量の数値は、０日目の溶液中の葉酸量を「１００」とする相対値にて示す。 The measurement results of the amount of folate in each solution after storage are shown in Table 2 below. In addition, the numerical value of the amount of folic acid in a table | surface is shown by the relative value which makes the amount of folic acid in the solution of the 0th day "100".
　表２に示すとおり、プロトン供与性有機溶媒であるエタノールを添加した比較例１Ｅ～７Ｅにおいて、葉酸の分解速度が顕著に増大したことが確認された。 As shown in Table 2, in Comparative Examples 1E to 7E to which ethanol which is a proton donating organic solvent was added, it was confirmed that the decomposition rate of folic acid was significantly increased.
　一方、溶解パラメーター（ＳＰ値）がエタノールと同程度であるアセトニトリル（ＳＰ値、エタノール：１２．７、アセトニトリル：１１．９）を添加した比較例１Ａ～７Ａにおいては、実施例と同程度の葉酸量が確認され、アセトニトリルの添加により葉酸の分解速度が顕著に増大することは認められなかった。 On the other hand, in Comparative Examples 1A to 7A in which acetonitrile (SP value, ethanol: 12.7, acetonitrile: 11.9) having the same solubility parameter (SP value) as that of ethanol was added, folic acid was comparable to that of the example. The amount was confirmed, and no significant increase in the degradation rate of folic acid was observed with the addition of acetonitrile.
　これらの結果は、比較例１Ｅ～７Ｅにおいて認められる葉酸の分解速度の増大が、葉酸の溶媒に対する溶解度に由来するものではなく、エタノール添加に基づく、エタノールの存在に由来するものであることを示す。 These results indicate that the increase in the degradation rate of folic acid observed in Comparative Examples 1E to 7E is not derived from the solubility of folic acid in the solvent but is derived from the presence of ethanol based on the addition of ethanol. .
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
ＩＩＩ．試験２：エタノール添加の影響（２）
　下記表３に示す組成にしたがって、ベース液、及びエタノールを含み、ｐＨを３．５とする溶液（実施例８、９、比較例８Ｅ）をそれぞれ調製した（０日目）。 III. Test 2: Effect of ethanol addition (2)
According to the composition shown in Table 3 below, solutions (Examples 8 and 9, Comparative Example 8E) containing a base solution and ethanol and having a pH of 3.5 were prepared (Day 0).
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000005
　各溶液を上記試験１と同様に、レトルトパウチに充填、殺菌、保存し、保存後の各溶液中の葉酸量をＨＰＬＣにより測定した。 Each solution was filled in a retort pouch, sterilized, stored as in the above-mentioned test 1, and the amount of folate in each solution after storage was measured by HPLC.
　保存後の各溶液中の葉酸量の測定結果を下記表４に示す。なお、表中の葉酸量の数値は、０日目の溶液中の葉酸量を「１００」とする相対値にて示す。 The measurement results of the amount of folate in each solution after storage are shown in Table 4 below. In addition, the numerical value of the amount of folic acid in a table | surface is shown by the relative value which makes the amount of folic acid in the solution of the 0th day "100".
　表４に示すとおり、エタノールの添加によって保存後の葉酸量の低下が認められたが（上記表２の実施例４と比較）、エタノールを０．０３重量％及び０．０５重量％含む実施例８及び９と比べて、エタノールを０．５重量％含む比較例８Ｅにおいては、保存後の葉酸量が顕著に低いことが確認された。一方、実施例８及び９との間で、保存後の葉酸量に大きな差は認められなかった。 As shown in Table 4, a decrease in the amount of folic acid after storage was observed by the addition of ethanol (compared to Example 4 in Table 2 above), but an example containing 0.03% by weight and 0.05% by weight of ethanol In Comparative Example 8E containing 0.5% by weight of ethanol, it was confirmed that the amount of folate after storage was significantly lower than that of 8 and 9. On the other hand, no significant difference was observed in the amount of folic acid after storage between Examples 8 and 9.
　この結果より、エタノールの含量が多いほど葉酸の分解速度が大きいことが確認されるが、エタノールの含量が０．０５重量％以下となる場合には、葉酸の分解速度があまり変化しないことが示唆される。 From this result, it is confirmed that the decomposition rate of folic acid is higher as the content of ethanol is larger, but it is suggested that the decomposition rate of folic acid does not change much when the content of ethanol is 0.05 wt% or less Be done.
Figure JPOXMLDOC01-appb-T000006
Figure JPOXMLDOC01-appb-T000006
ＩＶ．試験３：エタノール添加の影響（３）
　下記表５に示す組成にしたがって、葉酸を含む溶液（実施例１０、比較例９Ｅ）をそれぞれ調製した（０日目）。なお、香料１はエタノールを含まず中鎖脂肪酸とグリセリン脂肪酸エステルを溶媒として用いて、溶液化した香料であり、香料２は溶媒としてエタノールを５０重量％（最終製品濃度０．１重量％）含む香料である。 IV. Test 3: Effect of ethanol addition (3)
According to the composition shown in Table 5 below, solutions containing folic acid (Example 10, Comparative Example 9E) were prepared (Day 0). In addition, the fragrance 1 is a solution made by using medium-chain fatty acid and glycerin fatty acid ester as a solvent without containing ethanol, and the fragrance 2 contains 50% by weight of ethanol as a solvent (final product concentration 0.1% by weight) It is a perfume.
Figure JPOXMLDOC01-appb-T000007
Figure JPOXMLDOC01-appb-T000007
　各溶液を上記試験１と同様に、殺菌、保存し、保存後の各溶液中の葉酸量をＨＰＬＣにより測定した。 Each solution was sterilized and stored as in Test 1 above, and the amount of folate in each solution after storage was measured by HPLC.
　保存後の各溶液中の葉酸量の測定結果を下記表６に示す。なお、表中の葉酸量の数値は、０日目の溶液中の葉酸量を「１００」とする相対値にて示す。 The measurement results of the amount of folate in each solution after storage are shown in Table 6 below. In addition, the numerical value of the amount of folic acid in a table | surface is shown by the relative value which makes the amount of folic acid in the solution of the 0th day "100".
　表６に示すとおり、香料に含まれるという形にしてもエタノールが添加されることによって、溶液中の葉酸の分解速度は増大することが確認された。 As shown in Table 6, it was confirmed that the decomposition rate of folic acid in the solution was increased by the addition of ethanol even in the form of being contained in a perfume.
　一般的に、飲料や水系食品においては、分散性を高めるために香料はエタノール含有製剤が用いられている。しかしながら、上記の結果より、葉酸の分解速度を低減し、安定化を図るためには、エタノールを含有しない香料を用いること、すなわち、エタノールを含有しない原材料を用いることが有利であることが示された。 Generally, in beverages and water-based foods, ethanol-containing preparations are used as flavoring agents to enhance dispersibility. However, the above results show that it is advantageous to use an ethanol-free perfume, ie, to use ethanol-free raw materials, in order to reduce the rate of folic acid degradation and to achieve stabilization. The
Figure JPOXMLDOC01-appb-T000008
Figure JPOXMLDOC01-appb-T000008
＜ビタミンＢ１２の安定性の向上＞
（標品作成方法）
　予め４００μｇ／ｍＬに調整したＢ１２標準溶液５ｍｇを褐色メスフラスコに精秤し、水で２００ｍＬに希釈定容した。さらに、希釈定容した溶液の４ｍＬを褐色メスフラスコに精秤し、水で１００ｍＬに希釈定容し、ＨＰＬＣ測定における検量線作成のための標準溶液とした。
（ＨＰＬＣ測定前処理方法）
　ビタミンＢ１２を含む溶液サンプル２５ｇを褐色メスフラスコに精秤した。下記に記載する調整済み試薬を添加後、沸騰水中で３０分間の加熱を行った。 <Improving the stability of vitamin B 12 >
(How to make standard product)
5 mg of B 12 standard solution previously adjusted to 400 μg / mL was precisely weighed in a brown measuring flask and diluted to 200 mL with water. Further, 4 mL of the diluted solution was precisely weighed in a brown measuring flask, diluted with water to 100 mL, and used as a standard solution for preparing a calibration curve in HPLC measurement.
(HPLC pretreatment method)
The solution samples 25g containing vitamin B 12 was precisely weighed into a brown flask. After adding the adjusted reagent described below, heating was performed for 30 minutes in boiling water.
　　水　　　　　　　　　　　　　　　　：８０ｍＬ
　　酢酸ナトリウム緩衝液（ｐＨ４．５）：２０ｍＬ
　　シアン化カリウム（０．０５％）　　：　２ｍＬ
　加熱終了後に水冷却を行い、水で２００ｍＬに定容後、ＰＶＤＦフィルター（Ｗｈａｔｍａｎ　ＧＤ／Ｘ　Ｓｙｒｉｎｇｅ　Ｆｉｌｔｅｒ；直径２５ｍｍ、孔径０．４５μｍ）を用いて溶液を濾過した。次に、コンディショニング済み固相カラム（アジレント・テクノロジー社製　Ｂｏｎｄ　Ｅｌｕｔｅ　ＭＥＧＡ　ＢＥ－Ｃ１８）に濾液を２５ｍＬ通液した。試料液通液後の固相カラムに洗浄液１００ｍＬを通液した。洗浄は、酢酸ナトリウム緩衝液（ｐＨ４．５）を水で１０倍に希釈した溶液を通液することで行った。２５ｍＬ容ナシ型フラスコ内に固相カラム吸着物を、メタノールを用いて溶出した。日本ビュッヒ社製ロータリーエバポレーター（Ｒｏｔａｖａｐｏｒ（登録商標）　Ｒ－２１０）を用いて濃縮乾固した後、水１ｍＬを添加して残留物を再溶解した。溶解物をＣＡフィルター（ＭＳ　ＣＡ　Ｓｙｒｉｎｇｅ　Ｆｉｌｔｅｒ；直径１３ｍｍ、孔径０．４５μｍ）を用いて濾過し、試料溶液とした。
（ＨＰＬＣ測定条件）
　装置：日立ハイテクサイエンス製　ＬａＣｈｒｏｍ　Ｅｌｉｔｅ
　カラム：ＣＡＰＣＥＬＬＰＡＫ　Ｃ１８　ＵＧ１２０　５μｍ（３．０ｍｍφ×１５０ｍｍ）（資生堂）
温度：５０℃
流量：１．０ｍｌ／ｍｉｎ
注入量：２００μＬ
検出：紫外可視分光検出器　５５０ｎｍ
移動相：
Ａ：０．０５ｍｏｌ／Ｌ　ＫＨ２ＰＯ４（和光純薬工業株式会社）（ｐＨ２．１）
Ｂ：アセトニトリル（和光純薬工業株式会社）
Ａ／Ｂ＝９３／７
（ベース液調整方法）
　イオン交換水にグラニュー糖２．５％、果糖１．２％、Ｌ－アスコルビン酸０．８％、クエン酸０．２％、クエン酸三ナトリウム０．２％、ビタミンＢ１２０．０３２ｐｐｍになるように添加し、１．０Ｎ塩酸（和光純薬工業株式会社）、１．０Ｎ水酸化ナトリウム（和光純薬工業株式会社）を用いて目標ｐＨに調整しベース液とした。
（試験４）
　表７に示す組成の各溶液を、ビタミンＢ１２を含む溶液サンプルとしてＨＰＬＣ測定前処理方法に記載の方法で前処理して試料溶液とし、得られた試料溶液をＨＰＬＣ測定条件に従いＨＰＬＣ測定した。標準溶液を用いて作成した検量線を用い、ＨＰＬＣ測定値からビタミンＢ１２量を求め、０日目の値とし、これを１００％とした。表７に示す組成の各溶液を遮光されたレトルトパウチに約１００ｍＬ室温充填後、ＬＡＵＤＡ製恒温水槽（Ｄ２０ＫＰ）を使用して８０℃１０分間の湯殺菌を行った。殺菌後の各溶液を、ＡＤＶＡＮＴＥＣ社製恒温庫（ＡＧＸ－３４５）を使用して５０℃で保存し同様に０日目、３日目のビタミンＢ１２の測定を行った。 Water: 80 mL
Sodium acetate buffer (pH 4.5): 20 mL
Potassium cyanide (0.05%): 2 mL
After completion of heating, water cooling was performed, and the volume was adjusted to 200 mL with water, and then the solution was filtered using a PVDF filter (Whatman GD / X Syringe Filter; diameter 25 mm, pore diameter 0.45 μm). Next, 25 mL of the filtrate was passed through a conditioned solid phase column (Agilent Technology's Bond Elute MEGA BE-C18). 100 mL of the washing solution was passed through the solid phase column after sample solution passing. Washing was carried out by passing a solution of sodium acetate buffer (pH 4.5) diluted 10-fold with water. Solid phase column adsorbate was eluted using methanol in a 25 mL pear-shaped flask. After concentration to dryness using a rotary evaporator (Rotavapor (registered trademark) R-210) manufactured by Nippon Buchi, 1 mL of water was added to re-dissolve the residue. The lysate was filtered using a CA filter (MS CA Syringe Filter; diameter 13 mm, pore diameter 0.45 μm) to give a sample solution.
(HPLC measurement conditions)
Device: Hitachi High-Tech Science LaChrom Elite
Column: CAPCELLPAK C18 UG120 5μm (3.0mmφ × 150mm) (Shiseido)
Temperature: 50 ° C
Flow rate: 1.0 ml / min
Injection volume: 200 μL
Detection: UV-visible spectral detector 550 nm
Mobile phase:
A: 0.05 mol / L KH 2 PO 4 (Wako Pure Chemical Industries, Ltd.) (pH 2.1)
B: Acetonitrile (Wako Pure Chemical Industries, Ltd.)
A / B = 93/7
(Base solution adjustment method)
Granulated sugar 2.5% in ion-exchanged water, 1.2% fructose, 0.8% L-ascorbic acid, 0.2% citric acid, trisodium citrate 0.2%, the vitamin B 12 0.032ppm Thus, the pH was adjusted to the target pH using 1.0 N hydrochloric acid (Wako Pure Chemical Industries, Ltd.) and 1.0 N sodium hydroxide (Wako Pure Chemical Industries, Ltd.) to prepare a base solution.
(Test 4)
Each solution having the composition shown in Table 7 was pretreated by the method described in the HPLC measurement pretreatment method as a solution sample containing vitamin B 12 to prepare a sample solution, and the obtained sample solution was subjected to HPLC measurement according to HPLC measurement conditions. The amount of vitamin B 12 was determined from the HPLC measurement value using a calibration curve prepared using a standard solution, and was taken as the value on day 0, and this was taken as 100%. About 100 mL of each solution having the composition shown in Table 7 was filled into a light-shielded retort pouch at room temperature, and then sterilized with hot water at 80 ° C. for 10 minutes using a thermostatic water tank (D20KP) made by LAUDA. Each solution after sterilization was stored at 50 ° C. using a thermostatic container (AGX-345) manufactured by ADVANTEC, and vitamin B 12 was measured on day 0 and day 3 in the same manner.
Figure JPOXMLDOC01-appb-T000009
Figure JPOXMLDOC01-appb-T000009
　結果を表８に示す。表８の結果より、プロトン供与性有機溶媒であるエタノールを添加した比較例１ＥのみがビタミンＢ１２の分解を促進した。溶解パラメーター（ＳＰ値、エタノール：１２．７、アセトニトリル：１１．９）がほぼ同等であるアセトニトリルを添加した比較例１Ａはほぼ実施例と同様の分解率となった。このことからビタミンＢ１２の溶解度の影響はほぼなく、ビタミンＢ１２の分解促進はエタノール特有の現象でビタミンＢ１２の分解機構からプロトン供与性が原因と推察された。 The results are shown in Table 8. From the results of Table 8, only Comparative Example 1E with the addition of ethanol as a proton-donating organic solvents promoted decomposition of vitamin B 12. Comparative Example 1A in which acetonitrile having substantially the same solubility parameter (SP value, ethanol: 12.7, acetonitrile: 11.9) was added had almost the same decomposition rate as the example. This almost no effect on the solubility of the vitamin B 12 from accelerated degradation of vitamin B 12 is a proton-donating from degradation mechanism of vitamin B 12 in ethanol peculiar phenomenon was presumed to cause.
Figure JPOXMLDOC01-appb-T000010
Figure JPOXMLDOC01-appb-T000010
＜ビオチンの安定性の向上＞
（測定方法）
「食品表示基準について別添　栄養成分等の分析方法等」（平成２７年３月３０日消食表第１３９号消費者庁次長通知）に示される公定法に準ずる方法（微生物学的定量法）でビオチンの測定を行った。
（ベース液調整方法）
　イオン交換水にグラニュー糖２．５％、果糖１．２％、Ｌ－アスコルビン酸０．８％、クエン酸０．２％、クエン酸三ナトリウム０．２％、ビオチン０．３ｐｐｍになるように添加し、１．０Ｎ塩酸（和光純薬工業株式会社）、１．０Ｎ水酸化ナトリウム（和光純薬工業株式会社）を用いて目標ｐＨに調整しベース液とした。
（試験例５）
　表９に示す組成の各溶液を公定法に準ずる微生物学的定量法に従いビオチン量を測定した。各溶液についてのビオチン量の測定値を０日目の値とし、これを１００％とした。表９に示す組成の各溶液を遮光されたレトルトパウチに約１００ｍＬ室温充填後、ＬＡＵＤＡ製恒温水槽（Ｄ２０ＫＰ）を使用して８０℃１０分間の湯殺菌を行った。殺菌後の各溶液を、ＡＤＶＡＮＴＥＣ社製恒温庫（ＡＧＸ－３４５）を使用して５０℃で保存し同様に０日目および３日目のビオチンの測定を行った。 <Improvement of stability of biotin>
(Measuring method)
By method (microbiological quantitative method) based on official method shown in "analytical method such as attachment attached nutrient ingredient about food indication standard" (notice of March 30, 2015 consumption chart No. 139 consumer agency deputy director) The measurement of biotin was performed.
(Base solution adjustment method)
Ion-exchange water to be 2.5% granulated sugar, 1.2% fructose, 1.2% L-ascorbic acid, 0.2% citric acid, 0.2% citric acid, 0.2% trisodium citrate, 0.3 ppm biotin The solution was adjusted to a target pH using 1.0 N hydrochloric acid (Wako Pure Chemical Industries, Ltd.) and 1.0 N sodium hydroxide (Wako Pure Chemical Industries, Ltd.) to obtain a base solution.
Test Example 5
The amount of biotin was measured according to the microbiological determination method according to the official method for each solution of the composition shown in Table 9. The measured value of the amount of biotin for each solution was taken as the value on day 0, which was taken as 100%. About 100 mL of each solution having the composition shown in Table 9 was filled into a light-shielded retort pouch at room temperature, and then sterilized with hot water at 80 ° C. for 10 minutes using a thermostatic water tank (D20KP) made by LAUDA. Each solution after sterilization was stored at 50 ° C. using a thermostatic container (AGX-345) manufactured by ADVANTEC Co., Ltd., and the measurement of biotin at day 0 and day 3 was performed similarly.
Figure JPOXMLDOC01-appb-T000011
Figure JPOXMLDOC01-appb-T000011
　結果を表１０に示す。これより、プロトン供与性有機溶媒であるエタノールを添加した比較例１Ｅのみが各ｐＨ域でビオチンの分解を促進した。溶解パラメーター（ＳＰ値、エタノール：１２．７、アセトニトリル：１１．９）がほぼ同等であるアセトニトリルを添加した比較例１Ａはほぼ実施例と同様の分解率となった。このことからビオチンの溶解度の影響はほぼなく、ビオチンの分解促進はエタノール特有の現象でビオチンの分解機構からプロトン供与性が原因と推察された。 The results are shown in Table 10. From this, only Comparative Example 1E in which ethanol, which is a proton donating organic solvent, was added promoted the decomposition of biotin in each pH range. Comparative Example 1A in which acetonitrile having substantially the same solubility parameter (SP value, ethanol: 12.7, acetonitrile: 11.9) was added had almost the same decomposition rate as the example. From this, the influence of the solubility of biotin was almost nonexistent, and it was speculated that the acceleration of biotin degradation was caused by the proton donating property from the degradation mechanism of biotin, which is a phenomenon unique to ethanol.
Figure JPOXMLDOC01-appb-T000012
Figure JPOXMLDOC01-appb-T000012
　本明細書で引用した全ての刊行物、特許及び特許出願はそのまま引用により本明細書に組み入れられるものとする。 All publications, patents and patent applications cited herein are incorporated herein by reference in their entirety.

Claims (12)

  1. 　葉酸、ビタミンＢ１２及びビオチンからなる群から選択される１種以上を含有する酸性組成物であって、エタノールの含有量が０．１重量％未満であることを特徴とする、組成物。 An acidic composition comprising one or more selected from the group consisting of folic acid, vitamin B 12 and biotin, wherein the content of ethanol is less than 0.1% by weight.
  2. 　エタノール、グリセリン、メタノール、酢酸、ギ酸及びブチルアミンの含有量が合計で０．１重量％未満である、請求項１に記載の組成物。 The composition according to claim 1, wherein the total content of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine is less than 0.1% by weight in total.
  3. 　プロトン性有機溶媒の含有量が合計で０．１重量％未満である、請求項２に記載の組成物。 The composition according to claim 2, wherein the content of the protic organic solvent is less than 0.1% by weight in total.
  4. 　容器詰め飲料又は容器詰めゼリー飲料である、請求項１～３のいずれか一項に記載の組成物。 The composition according to any one of claims 1 to 3, which is a container-packed beverage or a container-packed jelly beverage.
  5. 　葉酸、ビタミンＢ１２及びビオチンからなる群から選択される１種以上を含有する酸性組成物の製造方法であって、エタノールの量が０．１重量％未満となるように原材料を配合することを含む、方法。 A method for producing an acidic composition containing one or more selected from the group consisting of folic acid, vitamin B 12 and biotin, which comprises blending raw materials so that the amount of ethanol is less than 0.1% by weight. The way, including.
  6. 　エタノール、グリセリン、メタノール、酢酸、ギ酸及びブチルアミンの量が合計で０．１重量％未満となるように原材料を配合することを含む、請求項５に記載の方法。 The method according to claim 5, comprising blending the raw materials so that the total amount of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine is less than 0.1% by weight.
  7. 　プロトン性有機溶媒の量が合計で０．１重量％未満となるように原材料を配合することを含む、請求項６に記載の方法。 The method according to claim 6, comprising blending the raw materials such that the total amount of protic organic solvent is less than 0.1% by weight.
  8. 　前記組成物が容器詰め飲料又は容器詰めゼリー飲料である、請求項５～７のいずれか一項に記載の方法。 The method according to any one of claims 5 to 7, wherein the composition is a container-packed beverage or a container-packed jelly beverage.
  9. 　酸性組成物中における葉酸、ビタミンＢ１２及びビオチンからなる群から選択される１種以上の安定性を向上させる方法であって、前記組成物中に含まれるエタノールの量を０．１重量％未満とすることを含む、方法。 A method for improving the stability of one or more selected from the group consisting of folic acid, vitamin B 12 and biotin in an acidic composition, wherein the amount of ethanol contained in said composition is less than 0.1% by weight And how to do it.
  10. 　前記組成物中に含まれるエタノール、グリセリン、メタノール、酢酸、ギ酸及びブチルアミンの量を合計で０．１重量％未満とすることを含む、請求項９に記載の方法。 10. A method according to claim 9, comprising total less than 0.1 wt% of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine contained in the composition.
  11. 　前記組成物中に含まれるプロトン性有機溶媒の量を合計で０．１重量％未満とすることを含む、請求項１０に記載の方法。 11. A method according to claim 10, comprising bringing the total amount of protic organic solvents contained in the composition to less than 0.1% by weight.
  12. 　前記組成物が容器詰め飲料又は容器詰めゼリー飲料である、請求項９～１１のいずれか一項に記載の方法。 The method according to any one of claims 9 to 11, wherein the composition is a container-packed beverage or a container-packed jelly beverage.
PCT/JP2017/047020 2017-12-25 2017-12-27 Vitamin-b-group-compound-containing acidic composition demonstrating excellent vitamin b group compound stability WO2019130499A1 (en)

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JP2007215498A (en) * 2006-02-17 2007-08-30 Otsuka Pharmaceut Co Ltd Drink for pregnant woman
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JP2007215498A (en) * 2006-02-17 2007-08-30 Otsuka Pharmaceut Co Ltd Drink for pregnant woman
JP2017014287A (en) * 2010-05-07 2017-01-19 エイワイファーマ株式会社 Method for stabilizing nutrient infusion solution for intravenous administration after high pressure steam sterilization
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