JP7036504B2 - Biotin-containing acidic composition with excellent biotin stability - Google Patents

Description

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

Biotin is a member of the B vitamins and is also referred to as vitamin H or coenzyme E. Biotin catalyzes a carboxylation reaction as a coenzyme of carboxylase in vivo. Carboxylation reactions are involved in gluconeogenesis, branched chain amino acids, fatty acid synthesis, energy metabolism and the like. A composition containing biotin is on the market.

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

Patent Document 2 describes that the stability of biotin is improved by further adding Toshishi extract to a liquid preparation containing biotin and vitamin B2.

Patent Document 3 describes that since biotin is unstable in the presence of reducing sugar (for example, sugar) in an internal liquid preparation, it may be preferable to add sugar alcohol as a sweetening agent.

According to Patent Document 4, biotin is decomposed when biotin is added to an oral solution containing a sweetener such as sugar at pH 2 to 5, and therefore biotin can be stabilized by adding a stevia extract as a sweetener. Are listed.

Patent Document 5 describes that biotin is stabilized by containing sucralose in an oral solution containing biotin.

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

Japanese Unexamined Patent Publication No. 2017-95372 Japanese Unexamined Patent Publication No. 2006-89430 Japanese Unexamined Patent Publication No. 10-265369 Japanese Unexamined Patent Publication No. 9-10425 Japanese Unexamined Patent Publication No. 2001-10955 Japanese Unexamined Patent Publication No. 7-76520

Patent Documents 1 to 6 presuppose that biotin and other components are blended in the composition for stabilization, and the uses and forms of supplements and beverages may be limited. In the art, techniques for improving the stability of biotin in acidic compositions are still eagerly desired.

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

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

The present invention is based on these findings and includes the following inventions.
[1] 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.
[3] The composition according to [2], wherein the content of the protonic 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 packaged beverage or a packaged jelly beverage.
[5] A method for producing an acidic composition containing biotin, which comprises blending 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 the protonic 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 packaged beverage or a packaged jelly beverage.
[9] A method for improving the stability of biotin in an acidic composition, which comprises reducing the amount of ethanol contained in the composition to less than 0.1% by weight.
[10] The method according to [9], wherein the total amount of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine contained in the composition is less than 0.1% by weight.
[11] The method according to [10], wherein the total amount of the protonic 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 packaged beverage or a packaged jelly beverage.

According to the present invention, it is possible to provide a biotin-containing acidic composition in which the decomposition 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 having excellent storage stability and capable of efficiently ingesting biotin.

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

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 the compound represented by the following structural formula:

Alternatively, it means a derivative thereof or a salt thereof that is acceptable in medicines and foods and drinks.

Biotin may be extracted or purified from food or chemically synthesized. The food containing biotin is not particularly limited, and examples thereof include bean and cereals such as bovine liver, egg yolk, and soybean.

The composition of the present invention may appropriately contain 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. 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, 70 μg per oral ingestion. As described above, it can be appropriately included in the range of 100 μg or more. For example, the range including the biotin intake (day) recommended by the "Japanese Dietary Intake Standards (2015 Edition)" published by the Ministry of Health, Labor and Welfare is preferable. The "single oral intake" is an amount in which the above composition is orally ingested at one time, or a plurality of consecutive times with a short time interval (for example, 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 semi-solid (gel, 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, etc.) 400 mL, 450 mL or 500 mL) is the amount. The upper limit of the amount of biotin contained in one oral intake is not particularly limited, and can be appropriately determined from the range of, for example, 1000 μg or less, 500 μg or less, 400 μg or less, 300 μg or less, 200 μg or less, and 150 μg or less.

In the present invention, the "protonic organic solvent" means an organic solvent that dissociates by itself to generate protons, and has an atom having a large electronegativity, that is, a hydrogen atom bonded to a nitrogen atom or an oxygen atom. Means. Examples of such a protonic organic solvent 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 rate of biotin degradation in acidic compositions. Therefore, by reducing the amount of ethanol contained in the acidic composition, the decomposition 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 glycerin, methanol, acetic acid, formic acid and butylamine, which are protonic organic solvents like ethanol, have the effect of increasing the decomposition rate of biotin, and therefore ethanol contained in the acidic composition is preferable. By reducing the total amount of glycerin, methanol, acetic acid, formic acid and butylamine, the rate of decomposition 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 the protic and aprotic organic solvents (including ethanol, glycerin, methanol, acetic acid, formic acid, butylamine, etc.) contained in the acidic composition. It can be reduced and the storage stability of biotin in an 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 biotin and / or enhance the storage stability, and the content of ethanol contained in the composition is preferable. The smaller the amount, the higher the storage stability of biotin in the composition. For example, by reducing the amount of ethanol contained in the conventional acidic composition containing biotin, the decomposition rate of biotin is reduced and / or the storage stability is reduced as compared with the conventional acidic composition. A high composition can be obtained. Therefore, the amount of ethanol contained in the composition of the present invention may be smaller than the amount of ethanol in the conventional acidic composition containing biotin, and is not particularly limited, but specifically. Can be 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. Particularly preferably, it can be in the range of 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 0.01% by weight or less.

The total amount of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine in the composition of the present invention is reduced as much as possible in order to further reduce the decomposition rate of biotin and / or further enhance storage stability. Is preferable. The total amount of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine in the composition of the present invention may be smaller than the total amount in the conventional acidic composition containing biotin, and is particularly limited. Although not, specifically, it is 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% by weight or less, 0.04% by weight or less, 0.03% by weight or less, 0.02% by weight or less, or 0.01% by weight or less.

The total amount of the protonic organic solvent containing ethanol, glycerin, methanol, acetic acid, formic acid, butylamine, etc. in the composition of the present invention is for further reducing the decomposition rate of biotin and / or further enhancing the storage stability. In addition, it is preferable to reduce it as much as possible. The total amount of the protic and aprotic organic solvent in the composition of the present invention may be smaller than the total amount in the conventional acidic composition containing biotin, and is not particularly limited, but is specific. Can be 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. Particularly preferably, it can be in the range of 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 0.01% by weight or less.

The terms "ethanol", "ethanol, glycerin, methanol, acetic acid, formic acid and butylamine" and "protic and aprotic organic solvent" in the present invention are not only compounded in the process of producing the acidic composition of the present invention, respectively. Also includes those that are blended / mixed in the process of manufacturing the raw materials used in the manufacture of the composition. For example, today, almost all types of perfume formulations contain ethanol (Uematsu et al., Sanitation Magazine, Vol.38, No.6, pp.452-459, December, 1997). However, for commercially available fragrance preparations, the diluent blended in the final product may be displayed, but it may not be displayed in the case of the solvent used for extracting the fragrance, and there are many types when formulating the fragrance preparation. Since the fragrance of the above is mixed, the solvent contained in the fragrance before mixing may not be displayed. Therefore, even if there is no indication that ethanol is contained in the fragrance preparation, it may actually be contained, and when such a fragrance preparation is blended in the composition of the present invention, it is contained in the composition. It can increase the ethanol content of the biotin and increase the rate of biotin degradation.

The amounts of "ethanol", "ethanol, glycerin, methanol, acetic acid, formic acid and butylamine" and "protic and aprotic organic solvent" in the composition of the present invention shall be measured by a conventionally known general method. Is possible. For example, the content of each solvent component in the composition is determined by gas chromatography using a solution obtained by mixing the composition with anhydrous sodium sulfate and acetonitrile, filtering the mixture, and dissolving the obtained filtrate in acetonitrile as an analysis sample. It can be obtained by attaching to (Kenji Isshiki, Shokuei Magazine. 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, pH less than 4.5, pH less than 4.4, pH less than 4.3, pH less than 4.2, pH4. It can be 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 depending on the form of the acidic composition. For example, pH 2.5 or higher, pH 2.6 or higher, pH 2.7 or higher, pH 2.8 or higher, pH 2 It can be 9.9 or higher, pH 3.0 or higher, pH 3.1 or higher, or pH 3.2 or higher.

When the acidic composition of the present invention is in the form of soft drink, the pH value is preferably less than pH 4.0. According to the Food Sanitation Law's food-specific standards, the methods for sterilizing and sterilizing soft drinks differ greatly from pH 4.0, and for sterilization of those with a pH of less than 4.0, the central temperature is set to 65 ° C. It is required to heat for 10 minutes, whereas for sterilization of those having a pH of 4.0 or higher, it is required to heat the central 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 in the sterilization step can be reduced and the decomposition of biotin in the sterilization step can be reduced, which is preferable. In the present specification, the pH value refers to a value measured at a product temperature of 20 ° C.

The pH value of the acidic composition of the present invention can be adjusted by appropriately adjusting the amount of the acidulant added. Examples of the acidulant include those commonly used in the production 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. One or a mixture of two or more of the above can be added.

In addition to biotin, the acidic composition of the present invention includes excipients, disintegrants, lubricants, binders, antioxidants, colorants, antioxidants, and absorption promoters that are acceptable as pharmaceuticals or foods and drinks. , Solvents, solubilizers, tonicity agents, stabilizers, flavoring agents, pH regulators, fragrance preparations, sweeteners, thickeners, preservatives, vitamins, agar and other raw materials such as the composition. It can be appropriately selected and blended according to the desired form of the product. However, it is preferable to use those components that do not contain ethanol or have a low ethanol content, and do not contain ethanol, glycerin, methanol, acetic acid, formic acid and butylamine, or have a low total content thereof. It is more preferable to use one that does not contain a protonic organic solvent (including ethanol, glycerin, methanol, acetic acid, formic acid, butylamine, etc.) or has a low total content of the protonic organic solvent. For example, as mentioned above, ethanol is contained as a solvent in almost all kinds of fragrance preparations today. In the present invention, instead of such a fragrance preparation, a fragrance preparation using one or more selected from medium-chain fatty acids and / or emulsifiers can be included instead of ethanol as a solvent. Here, although not particularly limited, C8, C10, C12 triglyceride and the like can be used as the medium chain fatty acid, and glycerin fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester and the like can be used as the emulsifier. Sucrose fatty acid esters and the like can be used.

The acidic composition of the present invention can be provided in the form of a pharmaceutical product (including quasi-drugs) or a food or drink. These forms can be in the form of a liquid composition or a semi-solid composition (gel-like, sol-like, etc.), and in addition to the above-mentioned biotin, the above-mentioned other raw materials may be appropriately added according to the dosage form. It can be blended and prepared according to a conventional method.

For example, the acidic composition of the present invention can be a packaged beverage. As the container for accommodating the acidic composition (liquid composition) of the present invention, a container used as a beverage container can be appropriately used, and the container is not limited, but is a polyethylene terephthalate (PET) container, a so-called PET bottle or the like. , Metal can containers and the like. The form of the container is not particularly limited. The capacity 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, 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 packaged jelly beverage. As the container for accommodating the acidic composition (semi-solid (gel-like, sol-like, etc.) composition of the present invention), a container used as a container for jelly beverages can be appropriately used, and the container is not limited, but is a resin. Examples include a film and / or a container made of a metal film, a pouch container, and the like. The capacity 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 if necessary, and water as a balance. The content of ethanol is less than the content of ethanol in conventional acidic compositions 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, Alternatively, it can be manufactured in the range of 0.01% by weight or less. The acidic composition according to a more preferred embodiment of the present invention comprises biotin extracted or purified from food, or chemically synthesized biotin, an acidulant, and optionally other raw materials as described above, as well as the balance. The total content of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine is less than the content of ethanol in conventional acidic compositions containing biotin, specifically 0.1. Less than% 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 be manufactured in the range of% by weight or less, 0.03% by weight or less, 0.02% by weight or less, or 0.01% by weight or less. The acidic composition according to a particularly preferred embodiment of the present invention includes biotin extracted or purified from food, or chemically synthesized biotin, an acidulant, and optionally other raw materials as described above, as well as the rest. The total content of the protonic organic solvent is smaller than the total content of the protonic organic solvent in the conventional acidic composition containing biotin, specifically 0.1% by weight. Less than, 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 less than 0.05% by weight, 0.04% by weight. Hereinafter, it can be manufactured in the range of 0.03% by weight or less, 0.02% by weight or less, or 0.01% by weight or less. The means for accommodating the acidic composition of the present invention in a container and sterilizing it can be arbitrarily selected.

Examples and test examples are shown below, and the present invention will be described in more detail, but the present invention is not limited to these examples.

<Example>
(Measuring method)
By the method (microbiological quantitative method) according to the official method shown in "Analysis method of nutritional components, etc. attached to food labeling standards" (Notice of Deputy Director of Consumer Affairs Agency, March 30, 2015) Biotin was measured.

(Base liquid adjustment method)
Add 2.5% granule sugar, 1.2% fructose, 0.8% L-ascorbic acid, 0.2% citric acid, 0.2% trisodium citrate, and 0.3 ppm biotin in ion-exchanged water. The mixture was added and adjusted to a target pH using 1.0N hydrochloric acid (Wako Pure Chemical Industries, Ltd.) and 1.0N sodium hydroxide (Wako Pure Chemical Industries, Ltd.) to prepare a base solution.

(Test Example 1)
The amount of biotin was measured for each solution having the composition shown in Table 1 according to a microbiological quantification method according to an official method. The measured value of the amount of biotin for each solution was set to the value on the 0th day, and this was set to 100%. Each solution having the composition shown in Table 1 was filled in a light-shielded retort pouch at room temperature at about 100 mL, and then sterilized with hot water at 80 ° C. for 10 minutes using a constant temperature water tank (D20KP) manufactured by LAUDA. Each solution after sterilization was stored at 50 ° C. using a constant temperature chamber (AGX-345) manufactured by ADVANTEC, and biotin was measured on the 0th and 3rd days in the same manner.

The results are shown in Table 2. From this, only Comparative Example 1E to which ethanol, which is a proton-donating organic solvent, was added promoted the decomposition of biotin in each pH range. Comparative Example 1A to which acetonitrile having substantially the same dissolution parameters (SP value, ethanol: 12.7, acetonitrile: 11.9) was added had a decomposition rate almost the same as that of the example. From this, the solubility of biotin had almost no effect, and the promotion of biotin decomposition was a phenomenon peculiar to ethanol, and it was inferred from the biotin decomposition mechanism that the proton donating property was the cause.

<Reference experiment>
I. Material / Measurement method 1. Standard stock solution 100 mg of folic acid was precisely weighed in a 200 mL brown beaker, and 5 mL of 0.1N sodium hydroxide solution (Wako Pure Chemical Industries, Ltd.) was added and dissolved. Next, 10 mL of special grade ethanol (Wako Pure Chemical Industries, Ltd.) was added and mixed, and then the pH of the solution was adjusted to 7.0 to 8.0 with 100 mL of ion-exchanged water and 0.1N hydrochloric acid (Wako Pure Chemical Industries, Ltd.). A 200 mL brown volumetric flask and ion-exchanged water were used to adjust the volume to a predetermined amount, and this was used as a standard stock solution for preparing a calibration curve in HPLC measurement.

2. 2. HPLC measurement The solution sample containing folic acid was weighed and then adjusted to pH 12.0 (HORIBA pH meter (F-72)) using 1.0N 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 1.0N hydrochloric acid (Wako Pure Chemical Industries, Ltd.) and filtered (AS ONE 0.45 μm filter (SY25TF). )), The obtained filtrate was subjected to HPLC measurement.

The HPLC measurement was carried out under the following conditions.
Equipment: Waters ACQUITY H-Class system Column: Waters XBridge C18 5 μm 6 × 250 mm
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% Na octasulfonic acid solution (Wako Pure Chemical Industries, Ltd.)

3. 3. Base solution In ion-exchanged water, granulated sugar 2.5% by weight, fructose 1.2% by weight, L-ascorbic acid 0.8% by weight, citric acid 0.2% by weight, trisodium citrate 0.2% by weight, and 0.0003% by weight of folic acid was added, and the pH was adjusted to a predetermined pH using 1.0N hydrochloric acid (Wako Pure Drug) and 1.0N sodium hydroxide (Wako Pure Drug) to prepare a base solution.

II. Reference test 1: Effect of addition of ethanol (1)
According to the composition shown in Table 3 below, a solution containing a base solution and ethanol or acetonitrile and having a predetermined pH (Reference Examples 1 to 7, Reference Comparative Examples 1E to 7E (with ethanol added), Reference Comparative Examples 1A to 1A to 5). 7A (added with acetonitrile)) were prepared respectively (day 0).

Each solution was filled in a light-shielded retort pouch at room temperature at 100 mL, and then sterilized with hot water at 80 ° C. for 10 minutes (LAUDA constant temperature water tank (D20KP)). Then, each solution was stored at 50 ° C. for a predetermined period (ADVANTEC constant temperature chamber (AGX-345)), and the amount of folic acid in each solution after storage was measured by HPLC.

The measurement results of the amount of folic acid in each solution after storage are shown in Table 4 below. The numerical value of the amount of folic acid in the table is shown as a relative value with the amount of folic acid in the solution on the 0th day as "100".

As shown in Table 4, it was confirmed that the decomposition rate of folic acid was remarkably increased in Reference Comparative Examples 1E to 7E to which ethanol, which is a proton-donating organic solvent, was added.

On the other hand, in Reference Comparative Examples 1A to 7A to which acetonitrile (SP value, ethanol: 12.7, acetonitrile: 11.9) having a dissolution parameter (SP value) similar to that of ethanol was added, the same degree as that of the reference example. The amount of folic acid was confirmed, and it was not observed that the rate of decomposition of folic acid was significantly increased by the addition of acetonitrile.

These results indicate that the increase in the rate of decomposition of folic acid observed in Reference Comparative Examples 1E to 7E is not due to the solubility of folic acid in the solvent, but to the presence of ethanol based on the addition of ethanol. show.

III. Reference test 2: Effect of addition of ethanol (2)
According to the composition shown in Table 5 below, a solution containing a base solution and ethanol and having a pH of 3.5 (Reference Examples 8 and 9, Reference Comparative Example 8E) was prepared (day 0).

Each solution was filled in a retort pouch, sterilized and stored in the same manner as in Reference Test 1, and the amount of folic acid in each solution after storage was measured by HPLC.

The measurement results of the amount of folic acid in each solution after storage are shown in Table 6 below. The numerical value of the amount of folic acid in the table is shown as a relative value with the amount of folic acid in the solution on the 0th day as "100".

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

From this result, it is confirmed that the higher the ethanol content, the higher the folic acid decomposition rate, but when the ethanol content is 0.05% by weight or less, it is suggested that the folic acid decomposition rate does not change much. Will be done.

IV. Reference test 3: Effect of addition of ethanol (3)
Solutions containing folic acid (Reference Example 10, Reference Comparative Example 9E) were prepared according to the compositions shown in Table 7 below (day 0). The fragrance 1 is a fragrance that is liquefied by using a medium-chain fatty acid and a glycerin fatty acid ester as a solvent without containing ethanol, and the fragrance 2 contains 50% by weight of ethanol (final product concentration 0.1% by weight) as a solvent. It is a fragrance.

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

The measurement results of the amount of folic acid in each solution after storage are shown in Table 8 below. The numerical value of the amount of folic acid in the table is shown as a relative value with the amount of folic acid in the solution on the 0th day as "100".

As shown in Table 8, it was confirmed that the rate of decomposition of folic acid in the solution was increased by adding ethanol even if it was contained in the fragrance.

Generally, in beverages and water-based foods, ethanol-containing preparations are used as flavors in order to enhance dispersibility. However, from the above results, it is shown that it is advantageous to use an ethanol-free fragrance, that is, to use an ethanol-free raw material in order to reduce the decomposition rate of folic acid and stabilize it. rice field.

Claims (12)

An acidic composition containing biotin and a fragrance preparation , wherein the fragrance preparation contains one or more selected from medium-chain fatty acids and / or emulsifiers as a solvent, and the content of ethanol is 0.1% by weight. A composition, characterized in that it is less than%. 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. The composition according to claim 2, wherein the content of the protonic 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 packaged beverage or a packaged jelly beverage. A method for producing an acidic composition containing biotin and a fragrance preparation , wherein the fragrance preparation contains one or more selected from medium-chain fatty acids and / or emulsifiers as a solvent, and the amount of ethanol is 0. A method comprising blending raw materials to be less than 1% by weight. The method according to claim 5, wherein the raw materials are blended 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, wherein the raw materials are blended so that the total amount of the protonic 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 packaged beverage or a packaged jelly beverage. A method for improving the stability of biotin in an acidic composition containing biotin and a fragrance preparation , wherein the fragrance preparation contains one or more selected from medium-chain fatty acids and / or emulsifiers as a solvent. The method used, which comprises making the amount of ethanol contained in the composition less than 0.1% by weight. The method according to claim 9, wherein the total amount of ethanol, glycerin, methanol, acetic acid, formic acid and butylamine contained in the composition is less than 0.1% by weight. The method according to claim 10, wherein the total amount of the protonic organic solvent contained in the composition is less than 0.1% by weight. The method according to any one of claims 9 to 11, wherein the composition is a packaged beverage or a packaged jelly beverage.