JP2019110828A - Biotin-containing acidic composition with excellent stability of biotin - Google Patents

Abstract

To provide a biotin-containing acidic composition with the decomposition of biotin being reduced and/or the stability of biotin being excellent.SOLUTION: A biotin-containing acidic composition has a reduced content of ethanol.SELECTED DRAWING: None

Description

  The present invention relates to a biotin-containing acidic composition in which the degradation rate of biotin is reduced and / or the stability of biotin is excellent.

  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.

  In Patent Document 1, in order to solve the problem that biotin is easily decomposed under vitamin B2 coexistence conditions, the stability of biotin is improved by further blending vitamin C into a liquid preparation containing biotin and vitamin B2. Is described.

  Patent Document 2 describes that the stability of biotin is improved by further blending a Toshishi extract into a solution containing biotin and vitamin B2.

  Patent Document 3 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.

  According to Patent Document 4, when biotin is incorporated into an internal solution of pH 2 to 5 containing a sweetener such as sugar, the biotin is decomposed. Therefore, by adding a stevia extract as a sweetener, biotin can be stabilized. Have been described.

  Patent Document 5 describes stabilization of biotin by incorporating sucralose in an internal solution containing biotin.

  Patent Document 6 describes that biotin is stabilized by containing polyvinyl pyrrolidone in a biotin-containing aqueous internal solution.

JP, 2017-95372, A JP, 2006-89430, A Japanese Patent Application Laid-Open No. 10-265369 JP-A-9-104625 JP, 2001-10955, A Japanese Patent Application Laid-Open No. 7-76520

  Patent Documents 1 to 6 presuppose that other components are blended in the composition together with biotin for stabilization, and the use and form of the supplement and the beverage may be limited. There remains a need in the art for techniques to improve the stability of biotin in acidic compositions.

  An object of the present invention is to provide a biotin-containing acidic composition in which the degradation rate of biotin is reduced and / or the stability of biotin is excellent.

  As a result of intensive studies to solve the above problems, the inventors of the present invention have found that biotin in the acidic composition has an increased decomposition rate due to the presence of ethanol, and / or its stability is I found it to decline. It has also been found that by reducing the amount of ethanol present in the acidic composition, the degradation rate of biotin is reduced and / or its stability is improved.

The present invention is based on these findings and includes the following inventions.
[1] A composition comprising an acidic composition containing biotin, wherein the content of ethanol is less than 0.1% by weight.
[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 biotin, comprising blending the raw materials so that the amount of ethanol is less than 0.1% by weight.
[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 of improving the stability of biotin in an acidic composition, comprising: setting the amount of ethanol contained in the composition to less than 0.1% by weight.
[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.

  According to the present invention, a biotin-containing acidic composition can be provided in which the degradation rate of biotin is reduced and / or the stability of biotin is excellent. According to the present invention, it is possible to provide a biotin-containing acidic composition which is excellent in storage stability and capable of efficiently taking in biotin.

  The present invention relates to an acidic composition comprising biotin and having a reduced content of ethanol.

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。 In the present invention, "biotin" is one of the essential water-soluble vitamins, and is a compound represented by the following structural formula:

Alternatively, it means an acceptable derivative thereof or a salt thereof in medicines and foods and beverages.

  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.

  Biotin can be suitably included in the composition of the present invention 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. 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. “One oral intake” refers to the amount of the above composition taken orally at a time, or a plurality of times continuously at short time intervals (eg, 10 minutes or less, preferably 5 minutes or less). It means the total amount taken orally. 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. 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.

  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.

  As detailed in the examples below, ethanol has the effect of increasing the degradation rate of biotin in the acidic composition. Therefore, by reducing the amount of ethanol contained in the acidic composition, the degradation rate of biotin in the acidic composition can be reduced, and the storage stability of biotin in the acidic composition can be enhanced. Not only ethanol but also the protic organic solvents glycerin, methanol, acetic acid, formic acid and butylamine as well as ethanol also have the effect of increasing the degradation rate of biotin, preferably ethanol contained in the acidic composition By reducing the total amount of glycerin, methanol, acetic acid, formic acid and butylamine, the degradation rate of biotin in the acidic composition can be reduced, and the storage stability of biotin in the acidic composition can be enhanced. . Particularly preferably, the decomposition rate of biotin 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. It can be reduced and the storage stability of biotin 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 degradation rate of biotin and / or enhance storage stability, and the content of ethanol contained in the composition is The lower the amount, the more storage stability of biotin in the composition can be. For example, by reducing the amount of ethanol contained relative to conventional acidic compositions containing biotin, the rate of degradation of biotin is reduced and / or storage stability compared to conventional acidic compositions A high composition can be obtained. Therefore, the amount of ethanol contained in the composition of the present invention may be a small amount as compared to the amount of ethanol in the conventional acidic composition containing biotin, and is not particularly limited. May be in the range of less than 0.1 wt%, such as 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 reduces the degradation rate of biotin further and / or as much as possible to further enhance storage stability. Is preferred. 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 biotin, and is particularly limited. Although not specifically, it is specifically in the range of 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 be able to. 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, etc., further reduces the decomposition rate of biotin and / or further enhances storage stability. It is preferable to reduce as much as possible. 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 biotin, and is not particularly limited, but it is specifically Can 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.

  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. The ethanol content of can be increased and the degradation rate of biotin can be increased.

  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 (Kenji Isshiki, Food Safety. Vol. 26, No. 1, pp. 39-45, 1985).

  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.

  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 degradation of biotin 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.

  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.

  In the acidic composition of the present invention, in addition to biotin, pharmaceutically or food-acceptable excipients, disintegrants, lubricants, binders, antioxidants, colorants, anticoagulants, absorption enhancers , Other raw materials such as solvents, solubilizers, tonicity agents, stabilizers, flavoring agents, pH adjusters, flavor preparations, sweeteners, thickeners, preservatives, vitamins, agar, etc. It can be appropriately selected and blended according to the form desired for the product. 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.

  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 can be in the form of liquid compositions or semisolid compositions (gel-like, sol-like, etc.), etc. In addition to the above-mentioned biotin, the above-mentioned other raw materials can be suitably selected according to the dosage form. It can be formulated and prepared according to a conventional method.

  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 is, for example, 50 to 500 mL (typically 50 mL, 100 mL, 150 mL, 180 mL, 200 mL, 200 mL, 250 mL, 300 mL, 350 mL, 400 mL, 450 mL or 500 mL), preferably 100 to 200 mL be able to.

  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).

  The acidic composition of the present invention is mixed with biotin extracted or purified from food or chemically synthesized biotin, an acidulant, other raw materials as described above as needed, and water as the balance. The content of ethanol is small compared to the content of ethanol in the conventional acidic composition containing biotin, specifically less than 0.1% by weight, for example, less than 0.09% by weight, 0.08% by weight Less than, 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, 0.03% by weight or less, 0.02% by weight or less, Or it can manufacture so that it may become the range of 0.01 weight% or less. The acidic composition according to a more preferred embodiment of the present invention is biotin extracted or purified from food, or chemically synthesized biotin, acidulant, other raw materials as described above as needed, and the balance Water is mixed, and the total content of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine is less than the content of ethanol in the conventional acidic composition containing biotin, specifically 0.1 Less than 0.09% by weight, eg 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 less than 0.05% by weight, 0.04 It can manufacture so that it may become the range of weight% or less, 0.03 weight% or less, 0.02 weight% or less, or 0.01 weight% or less. The acidic composition according to a particularly preferred embodiment of the present invention is biotin extracted or purified from food, or chemically synthesized biotin, an acidulant, other raw materials as mentioned above as needed, and the balance Water is mixed as the total content of the protic organic solvent is small compared to the total content of the protic organic solvent in the conventional acidic composition containing biotin, specifically 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 not more than 0.05% by weight, 0.04% by weight Hereinafter, it can manufacture so that it may become 0.03 weight% or less, 0.02 weight% or less, or 0.01 weight% or less range. Means for containing the acidic composition of the present invention in a container and means for sterilization can be optionally selected.

  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.

<Example>
(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% 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 1)
The amount of biotin was measured according to a microbiological determination method according to a standard method for each solution of the composition shown in Table 1. 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 1 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 (D20 KP) made by LAUDA. Each solution after sterilization was stored at 50 ° C. using a thermostatic container (AGX-345) manufactured by ADVANTEC, and the measurement of biotin at day 0 and day 3 was performed similarly.

  The results are shown in Table 2. 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.

<Reference experiment>
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.). Next, after stirring for 10 minutes (magnetic stirrer (RSH-1AN) manufactured by AS ONE), 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.

The HPLC measurement was performed under the following conditions.
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. Reference test 1: Influence of ethanol addition (1)
A solution containing a base solution and ethanol or acetonitrile according to the composition shown in the following Table 3 and having a predetermined pH (Reference Examples 1 to 7, Reference Comparative Examples 1E to 7E (ethanol added), Reference Comparative Examples 1A to 7A (acetonitrile added) 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 storage (AGX-345)), and the amount of folate in each solution after storage was measured by HPLC.

  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".

  As shown in Table 4, in Reference 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.

  On the other hand, in Reference Comparative Examples 1A to 7A to which acetonitrile (SP value, ethanol: 12.7, acetonitrile: 11.9) having the same solubility parameter (SP value) as ethanol was added, the same level as in the reference example was obtained. The amount of folic acid was confirmed, and the addition of acetonitrile did not significantly increase the degradation rate of folic acid.

  These results indicate that the increase in the decomposition rate of folic acid observed in Reference 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. Show.

III. Reference test 2: Effect of ethanol addition (2)
According to the composition shown in Table 5 below, solutions (Reference Examples 8 and 9 and Reference 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 and stored in the same manner as Reference Test 1 above, and the amount of folate in each solution after storage was measured by HPLC.

  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".

  As shown in Table 6, a decrease in the amount of folic acid after storage was observed by the addition of ethanol (compare with Reference Example 4 in Table 4 above), but a reference example containing 0.03 wt% and 0.05 wt% of ethanol It was confirmed that the amount of folate after storage was significantly lower in Reference Comparative Example 8E containing 0.5% by weight of ethanol as compared to 8 and 9. On the other hand, no significant difference was observed in the amount of folate after storage between Reference Examples 8 and 9.

  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.

IV. Reference test 3: Effect of ethanol addition (3)
According to the compositions shown in Table 7 below, solutions containing folic acid (Reference Example 10, Reference Comparative Example 9E) were respectively 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.

  Each solution was sterilized and stored in the same manner as Reference Test 1 above, and the amount of folate in each solution after storage was measured by HPLC.

  The measurement results of the amount of folate in each solution after storage are shown in Table 8 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".

  As shown in Table 8, 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.

  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

Claims (12)

  An acidic composition containing biotin, characterized in that the content of ethanol is less than 0.1% by weight.   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.   The composition according to claim 2, wherein the content of the protic organic solvent is less than 0.1% by weight in total.   The composition according to any one of claims 1 to 3, which is a container-packed beverage or a container-packed jelly beverage.   A method of producing an acidic composition containing biotin, comprising blending the raw materials such that the amount of ethanol is less than 0.1% by weight.   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.   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.   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.   A method of improving the stability of biotin in an acidic composition, comprising making the amount of ethanol contained in said composition less than 0.1% by weight.   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. 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.   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.