Method for improving the stability of 3-(4-hydroxy-3-methoxyphenyl)propionic acid and stability improver

Abstract

To provide a method for improving stability of a compound represented by a structural formula (1), which can improve stability of the compound represented by the structural formula (1) over time and stability against heat treatment, and to provide a stability improver.SOLUTION: There is provided a method for improving stability of a compound represented by a structural formula (1), which comprises coexisting a compound represented by a structural formula (A) with a compound represented by the structural formula (1), and there is also provided a stability improver which is used to improve the stability of the compound represented by the structural formula (1), wherein the stability improver contains the compound represented by the structural formula (A).SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for improving the stability of 3-(4-hydroxy-3-methoxyphenyl)propionic acid and a stability improver. [Background technology]

[0002] The name of the compound represented by the following structural formula (1) is 3-(4-hydroxy-3-methoxyphenyl)propionic acid. It is known that the compound represented by the following structural formula (1) can be detected when a certain type of lactic acid bacteria is cultured in a medium containing specific components (see, for example, Patent Document 1). [ka]

[0003] The compound represented by the structural formula (1) is an active ingredient of a dipeptidyl peptidase IV activity inhibitor, etc., and is a very useful ingredient known to be able to be incorporated into foods and beverages for inhibiting dipeptidyl peptidase IV activity (see, for example, Patent Document 2).

[0004] As described above, the compound represented by the structural formula (1) is a very useful component, but its stability over time and against heat treatment is not sufficient, and there is currently a strong demand for the prompt development of a technology that can improve its stability. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Laid-Open No. 2014-003929 [Patent Document 2] Japanese Patent Publication No. 2020-055887 Summary of the Invention [Problem to be solved by the invention]

[0006] The present invention aims to solve the above-mentioned conventional problems and achieve the following object: That is, the present invention aims to provide a method for improving the stability of a compound represented by structural formula (1) and a stability improver that can improve the stability of the compound represented by structural formula (1) over time and against heat treatment. [Means for solving the problem]

[0007] As a result of intensive research conducted by the present inventors to solve the above problems, it was found that when a compound represented by the following structural formula (1) and a compound represented by the following structural formula (A) are allowed to coexist, the stability of the compound represented by the following structural formula (1) over time, particularly the stability over time under light irradiation or at high temperatures, and the stability against heat treatment can be improved, and the present invention has been completed based on this finding. [ka] [ka]

[0008] The present invention is based on the above findings of the present inventors, and the means for solving the above problems are as follows: <1> A method for improving the stability of a compound represented by the following structural formula (1), comprising allowing a compound represented by the following structural formula (A) to coexist with a compound represented by the following structural formula (1): [ka] [ka] <2> The compound represented by the structural formula (1) is coexistent with 0.001 parts by mass or more of the compound represented by the structural formula (A). <1> This is a method for improving stability described in <3> The method for improving the stability of the compound represented by the structural formula (1) contained in food and drink. <1> from <2> The method is any one of the above. <4> A stability improver used to improve the stability of a compound represented by the following structural formula (1): The stability improver is characterized by containing a compound represented by the following structural formula (A). [ka] [ka] <5> The compound represented by the structural formula (A) is used in an amount of 0.001 part by mass or more relative to 1 part by mass of the compound represented by the structural formula (1). <4> It is a stability improver described in <6> The method for improving the stability of the compound represented by the structural formula (1) contained in food and drink. <4> from <5> The stability improver according to any one of the above items. [Effects of the Invention]

[0009] According to the present invention, the above-mentioned problems in the prior art can be solved, the above-mentioned objects can be achieved, and a method for improving the stability of a compound represented by structural formula (1) and a stability improver can be provided, which can improve the stability of the compound represented by structural formula (1) over time and against heat treatment. DETAILED DESCRIPTION OF THE INVENTION

[0010] (Method for improving the stability of a compound represented by structural formula (1)) The method of the present invention for improving the stability of a compound represented by structural formula (1) (hereinafter, sometimes referred to as the "stability improvement method") includes at least a coexistence step, and may further include other steps as necessary. In this specification, improving the stability of the compound represented by structural formula (1) means suppressing a decrease in the content of the compound represented by structural formula (1) over time or suppressing a decrease in the content of the compound represented by structural formula (1) due to heat treatment.

[0011] <Coexistence process> The coexistence step is a step in which the compound represented by structural formula (A) is allowed to coexist with the compound represented by structural formula (1). In the coexistence step, components other than the compound represented by the structural formula (A) and the compound represented by the structural formula (1) may be present.

[0012] -Compound represented by structural formula (1)- The name of the compound represented by the following structural formula (1) is 3-(4-hydroxy-3-methoxyphenyl)propionic acid (hereinafter sometimes referred to as "HMPA"). [ka]

[0013] The compound represented by the structural formula (1) is a known compound, and a commercially available product may be used, or one produced by a known method may be used.

[0014] -Compound represented by structural formula (A)- The name of the compound represented by the structural formula (A) is 4-hydroxy-3-methoxycinnamic acid (hereinafter, sometimes referred to as "HMCA"). [ka]

[0015] The compound represented by the structural formula (A) is a known compound, and a commercially available product may be used, or one produced by a known method may be used.

[0016] The amount of the compound represented by structural formula (A) used (amount to be coexisted) is not particularly limited and can be selected appropriately depending on the purpose, but it is preferable to use 0.001 parts by mass or more of the compound represented by structural formula (A) per 1 part by mass of the compound represented by structural formula (1), and more preferably 0.01 parts by mass or more. Being within this preferred range is advantageous in that the stability of the compound represented by structural formula (1) over time and its stability against heat treatment can be further improved. The upper limit of the amount of the compound represented by structural formula (A) used is not particularly limited as long as it does not impair the effects of the present invention, and can be selected appropriately depending on the purpose.

[0017] -Other ingredients- The other components are not particularly limited as long as they do not impair the effects of the present invention and can be appropriately selected depending on the application of the compound represented by structural formula (1), and examples thereof include excipients, moisture-proofing agents, preservatives, strengthening agents, thickeners, emulsifiers, antioxidants, sweeteners, acidulants, seasonings, coloring agents, fragrances, whitening agents, moisturizers, oily components, UV absorbers, surfactants, thickeners, alcohols, powder components, coloring agents, aqueous components, water, skin nutrients, components used in foods and beverages, etc. These may be used alone or in combination of two or more. The amounts of the other components used are not particularly limited and can be appropriately selected depending on the purpose.

[0018] -Coexistence- The coexistence method is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include a method of adding the compound represented by structural formula (A) to a system containing the compound represented by structural formula (1), a method of adding the compound represented by structural formula (1) to a system containing the compound represented by structural formula (A), a method of simultaneously adding the compound represented by structural formula (1) and the compound represented by structural formula (A) to the same system, etc. Any of these methods may be used alone, or two or more of them may be combined.

[0019] <Other processes> The other steps are not particularly limited as long as they do not impair the effects of the present invention, and can be appropriately selected depending on the purpose.

[0020] <Aspect> The form of the compound represented by the structural formula (1) is not particularly limited and can be appropriately selected depending on the purpose. Examples include forms in which the compound is contained in foods and beverages, and forms in which the compound is contained in various preparations such as dipeptidyl peptidase IV activity inhibitors. Furthermore, the inclusion containing the compound represented by the structural formula (1) may be liquid, solid, or semi-solid. The content of the compound represented by the structural formula (1) in the inclusion containing the compound represented by the structural formula (1) is not particularly limited and can be appropriately selected depending on the purpose.

[0021] The food and drink products are not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include beverages such as tea drinks, soft drinks, carbonated drinks, nutritional drinks, fruit drinks, and lactic acid drinks; frozen desserts such as ice cream, ice sherbet, and shaved ice; noodles such as soba, udon, vermicelli, gyoza wrappers, shumai wrappers, Chinese noodles, and instant noodles; sweets such as candy, candy, gum, chocolate, candy tablets, snacks, biscuits, jelly, jam, cream, baked goods, and bread; seafood such as crab, salmon, clams, tuna, sardines, shrimp, bonito, mackerel, whale, oysters, saury, squid, ark shells, scallops, abalone, sea urchin, salmon roe, and tokobushi; kamaboko, ham, These include processed seafood and livestock foods such as sausages; dairy products such as processed milk and fermented milk; oils and fats and processed oil foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressings; condiments such as sauces and dressings; retort pouch foods such as curry, stew, oyakodon (chicken and egg rice bowl), porridge, rice porridge, Chinese rice bowl, katsudon (pork cutlet bowl), tempura bowl, eel bowl, hayashi rice, oden, mapo dolphin, beef bowl, meat sauce, egg soup, omelet rice, gyoza (dumplings), shumai (steamed dumplings), hamburger steak, and meatballs; side dishes such as salads and pickles; health, beauty, and nutritional supplements in various forms; pharmaceuticals and quasi-drugs such as tablets, granules, capsules, drinks, and lozenges. The foods and beverages are not limited to those listed above.

[0022] The dosage form of the preparation is not particularly limited and can be appropriately selected depending on the purpose. Examples include oral administration preparations such as tablets, powders, capsules, granules, extracts, and syrups; parenteral administration preparations such as injections, drip infusions, and suppositories; and external preparations such as lotions, emulsions, creams, ointments, beauty serums, lotions, packs, jellies, lip balms, lipsticks, foundations, bath additives, soaps, body soaps, astringents, hair tonics, hair lotions, hair creams, hair liquids, pomades, shampoos, rinses, and conditioners.

[0023] According to the stability improving method of the present invention, the stability over time of the compound represented by structural formula (1), particularly the stability over time under light irradiation or at high temperatures, and the stability against heat treatment can be improved.

[0024] (Stability improver for compounds represented by structural formula (1)) The stability improver for the compound represented by structural formula (1) of the present invention (hereinafter, may be referred to as "stability improver") is a stability improver used to improve the stability of the compound represented by structural formula (1), and contains at least a compound represented by structural formula (A), and further contains other components as necessary.

[0025] <Compound represented by structural formula (A)> The compound represented by the structural formula (A) is the same as the compound represented by the structural formula (A) in the stability improving method of the present invention described above.

[0026] The content of the compound represented by structural formula (A) in the stability improver is not particularly limited and can be appropriately selected depending on the amount used, etc. The stability improver may consist solely of the compound represented by structural formula (A).

[0027] The amount of the compound represented by structural formula (A) used is not particularly limited and can be selected appropriately depending on the purpose, but it is preferable to use 0.001 parts by mass or more of the compound represented by structural formula (A) per 1 part by mass of the compound represented by structural formula (1), and more preferably 0.01 parts by mass or more. Being within this preferred range is advantageous in that the stability of the compound represented by structural formula (1) over time and its stability against heat treatment can be further improved. The upper limit of the amount of the compound represented by structural formula (A) used is not particularly limited as long as it does not impair the effects of the present invention, and can be selected appropriately depending on the purpose.

[0028] <Other ingredients> The other components are not particularly limited as long as they do not impair the effects of the present invention, and can be selected appropriately depending on the purpose. Examples include those described in the section on other components in the stability improvement method of the present invention above. The content of the other components in the stability improver is not particularly limited and can be appropriately selected according to the purpose.

[0029] According to the stability improver of the present invention, it is possible to improve the stability of the compound represented by the structural formula (1) over time, particularly the stability over time under light irradiation or high temperature, and the stability against heat treatment.

[0030] The compound represented by the structural formula (1) is the same as the compound represented by the structural formula (1) in the stability improvement method of the present invention described above. Also, the aspect of the compound represented by the structural formula (1) is the same as that described in the <Aspect> item in the stability improvement method of the present invention described above.

Examples

[0031] Hereinafter, test examples will be described, but the present invention is not limited to these test examples. In the following test examples, HMPA manufactured by Tokyo Chemical Industry Co., Ltd. was used, and HMCA and ascorbic acid manufactured by Fujifilm Wako Pure Chemical Corporation were used.

[0032] (Test Example 1: Light Irradiation) The HMPA standard product and the HMCA standard product were dissolved in water to a concentration of 0.1 mg / mL, and NaOH was added to adjust the pH to 3 or pH ⑥. Also, ascorbic acid was dissolved in water to a concentration of 10 mg / mL, and NaOH was added to adjust the pH to 3 or pH ⑥. Using these solutions, they were diluted to 500 mL so that the concentrations of HMPA, HMCA, and ascorbic acid were those shown in Tables 1-1 to 1-4 to obtain samples.

[0033] The samples were stored under light irradiation (14,000 lux, 25 °C) to confirm the stability of HMPA when HMCA was blended. The stability of HMPA was confirmed by measuring the amount of HMPA in the samples before and after storage under the following high performance liquid chromatography (HPLC) conditions and calculating the residual ratio of HMPA. The results are shown in Tables 1-1 to 1-4. <HPLC Conditions> Column: Wakosil-II 5C18 HG 4.6mm x 250mm (Fujifilm Wako Pure Chemical Industries, Ltd.) Mobile phase: Water (0.1% THF):Acetonitrile = 80:20 Flow rate: 1 mL / min · Temperature: 40℃ · Injection volume: 10μL · Wavelength: 280nm Autosampler: 15℃

[0034] [Table 1-1]

[0035] [Table 1-2]

[0036] [Table 1-3]

[0037] [Table 1-4]

[0038] (Test example 2: Stored at 40°C) HMPA and HMCA standards were dissolved in water to a concentration of 0.1 mg / mL, and NaOH was added to adjust the pH to 3 or 6. This solution was used to dilute HMPA and HMCA to 500 mL so that the concentrations shown in Tables 2-1 and 2-2 were obtained as samples. The stability of HMPA when blended with HMCA was confirmed in the same manner as in Test Example 1, except that the sample was stored at 40° C. The results are shown in Tables 2-1 to 2-2.

[0039] [Table 2-1]

[0040] [Table 2-2]

[0041] (Test Example 3: Sterilization) HMPA standard, HMCA standard, and ascorbic acid were dissolved in water to a concentration of 1 mg / mL, and NaOH was added to adjust the pH to 6. Using these solutions, HMPA, HMCA, and ascorbic acid were adjusted to the concentrations listed in Tables 3-1 and 3-2 to prepare samples. The sample was heated at 95°C for 1 hour. The stability of HMPA was confirmed by measuring the amount of HMPA before and after the heating in the same manner as in Test Example 1. The results are shown in Tables 3-1 and 3-2.

[0042] [Table 3-1]

[0043] [Table 3-2]

[0044] These results demonstrate that the coexistence of HMPA with HMCA improves the stability of HMPA, and that this stability improvement effect is greater than that achieved when HMPA is coexisted with ascorbic acid.

Claims

1. A method for improving the stability of a compound represented by the following structural formula (1), comprising causing a compound represented by the following structural formula (A) to coexist with a compound represented by the following structural formula (1): 【Chemical 1】 【Chemistry 2】

2. 2. The method for improving stability according to claim 1, wherein 0.001 parts by mass or more of the compound represented by structural formula (A) is coexistent with 1 part by mass of the compound represented by structural formula (1).

3. 3. The method according to claim 1, wherein the stability of the compound represented by the structural formula (1) contained in a food or drink is improved.

4. A stability improver used to improve the stability of a compound represented by the following structural formula (1): A stability improver comprising a compound represented by the following structural formula (A): 【Chemistry 3】 【Chemistry 4】

5. The stability improver according to claim 4, wherein the compound represented by structural formula (A) is used in an amount of 0.001 part by mass or more per part by mass of the compound represented by structural formula (1).

6. The stability improver according to claim 4 or 5, which improves the stability of a compound represented by the structural formula (1) contained in a food or drink.

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