Oral composition, food and beverage, cosmetic, supplement and pharmaceutical, and method for producing food and beverage

Abstract

To provide a novel oral composition including imidazole dipeptide, and an oral composition, fish meat, processed fish products, meat, processed meat products, food and beverages, and pharmaceuticals including the oral composition.SOLUTION: An oral composition of the present invention includes cyclic imidazole dipeptides and linear imidazole dipeptides. Additionally, in the oral composition, when the sum of a first molar number (mol / g) of the linear imidazole dipeptide per unit mass and a second molar number (mol / g) of the cyclic imidazole dipeptide per unit mass is defined as 1, the second molar number is more than 0.01.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to oral compositions, food and beverage products, cosmetics, supplements and formulations, and methods for producing foods and beverages that contain cyclic imidazole dipeptides. [Background technology]

[0002] Health enriches the lives of citizens and contributes to the creation of a vibrant society. Providing food, beverages, and preparations that can contribute to the maintenance or promotion of health is now an important issue in countries around the world. In recent years, imidazole dipeptides have been attracting attention as components that enhance human physiological functions, such as antioxidant and anti-fatigue effects (Non-Patent Document 1).

[0003] Imidazole dipeptides are known to be contained in chicken, pork, whale meat, and some seafood. There are mainly three types of substances classified as imidazole dipeptides (carnosine, anserine, and balenine). Among the imidazole dipeptides, anserine is found in large amounts in chicken, bonito, and tuna, for example. Recently, it has been found that the sunfish (also called "mandai") contains more balenine than the minke whale, a marine mammal (Patent Documents 1 to 5, Non-Patent Documents 2 and 3). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Patent No. 7471062 [Patent Document 2] Patent No. 7469007 [Patent Document 3] Patent No. 6587774 [Patent Document 4] Patent No. 6578465 [Patent Document 5] JP 2023-154520 A [Non-patent literature]

[0005] [Non-Patent Document 1] Nishitani, et al., "Review: New Anti-Fatigue Ingredients: Imidazole Dipeptides", Journal of the Japanese Society for Complementary and Alternative Medicine, Vol. 6, No. 3, October 2009, p123-129 [Non-Patent Document 2] Omura, et al., "Balenin content in muscle of the red sunfish Lampris guttatus", Abstracts of the 2018 Spring Meeting of the Japanese Society of Fisheries Science, March 26, 2018, p.92 [Non-Patent Document 3] Omura, et al., "Discovery of high content of balenine, which has fatigue suppression function, in sunfish," Research Movements (Collection of Major Results of the Central Fisheries Research Institute), September 2018, p. 11 Summary of the Invention [Problem to be solved by the invention]

[0006] As mentioned above, various studies have been conducted on the physiological or medical actions, efficacy and effects of imidazole dipeptides in animals (including humans; hereinafter, in this application, we will refer to them as "humans") that have ingested or retained imidazole dipeptides in their bodies. However, the inventors of this application are not aware of any prior applications, academic presentations or reports by others regarding the state of imidazole dipeptides in the wild or after various processing steps during the period from when they are subjected to primitive processing (e.g., fillets, sashimi, etc.) and become commercial products, to when they are ingested by humans, and regarding their cyclization. [Means for solving the problem]

[0007] The present invention greatly contributes to the realization of an oral composition containing a novel imidazole dipeptide that is different from conventionally known imidazole dipeptides, as well as processed products, food and beverages, supplements, preparations, and the like that contain the oral composition.

[0008] Taking the above circumstances into consideration, the present inventor analyzed the chemical structure and functionality of so-called natural imidazole dipeptides contained in processed products such as fillets and sashimi, as well as the chemical structure and functionality of imidazole dipeptides in processed products that have been subjected to treatments other than the above-mentioned primitive processing (heat treatment, freezing treatment, and / or drying treatment, etc.).

[0009] As a result of the inventor's repeated examination of the analytical results and further research, it was found that imidazole dipeptides having a cyclic chemical structure (hereinafter referred to as "cyclic imidazole dipeptides") different from the three known imidazole dipeptides (carnosine, anserine, and balenine) were identified in the processed products that were processed differently from the above-mentioned primitive processing. On the other hand, it is very interesting to note that the above-mentioned cyclic imidazole dipeptides were not identified in the analytical results of the above-mentioned primitive processed products.

[0010] Here, the above-mentioned "cyclic imidazole dipeptide" is an imidazole dipeptide that is considered to have three chemical structural formulas (A to C) shown in FIG. 1, in which a carboxyl group and an amino group at the end of a conventionally known imidazole dipeptide are cyclized by a peptide bond. In this application, (A) in FIG. 1 is called "cyclic carnosine", (B) is called "cyclic anserine", and (C) is called "cyclic balenine". Therefore, it can be said that a "cyclic imidazole dipeptide" is an imidazole dipeptide in which two peptide bonds are incorporated into the ring, in other words, an imidazole dipeptide having two peptide bonds in the ring. The term "cyclic" can be replaced with, for example, "cyclized", "cyclo", "cyclo", or "cyclic", but the term "cyclic" is adopted as a technical term in this application.

[0011] In addition, the three known imidazole dipeptides (carnosine, anserine, and balenine) shown in the chemical structural formulas (A' to C') in FIG. 2 can be expressed as "non-cyclic imidazole dipeptide", "linear imidazole dipeptide", or "linear imidazole dipeptide" to distinguish them from cyclic imidazole dipeptides. However, in the present application, "linear imidazole dipeptide" is typically adopted as the technical term. Therefore, the meaning of "linear imidazole dipeptide" in the present application includes "non-cyclic imidazole dipeptide" and "linear imidazole dipeptide". In addition, (A') in FIG. 2 is "linear carnosine", (B') is "linear anserine", and (C') is "linear balenine".

[0012] The present inventors further conducted research into the functionality, physiological or medical actions, efficacy and effects of the three new imidazole dipeptides that were discovered from the above-mentioned analytical results.

[0013] As a result, although there are still some unclear points, it was found that cyclic imidazole dipeptides or oral compositions containing cyclic imidazole dipeptides (hereinafter referred to as "cyclic imidazole dipeptides, etc." in this paragraph) may have different functionality and different effects on humans than linear imidazole dipeptides or oral compositions containing linear imidazole dipeptides (hereinafter referred to as "linear imidazole dipeptides, etc." in this paragraph. Specifically, it was found that cyclic imidazole dipeptides, etc. may have at least one or more characteristics selected from the following group (1) to (8) that are different from linear imidazole dipeptides, etc., or superior to linear imidazole dipeptides, etc. (1) Suppression of blood pressure rise in humans (2) Suppression of increases in neutral fat levels in human blood (3) Suppression of cognitive decline in humans (4) Improving human sleep quality (5) Reducing human stress (6) Suppression of increases in uric acid levels in humans (7) Improving human antioxidant capacity (8) Improve anti-fatigue ability in humans

[0014] In addition, according to the research and analysis of the present inventor, imidazole dipeptides are quickly absorbed into human blood vessels, but in order to make the above-mentioned characteristics or effects of imidazole dipeptides that can contribute to human health promotion last for a longer period of time, it is a preferable embodiment from the viewpoint of improving the durability of the characteristics or effects to have the imidazole dipeptides remain in the blood of a human for a longer period of time after ingestion by the human. Therefore, the present inventor conducted research focusing on the hydrophobicity (in other words, low hydrophilicity) of cyclic imidazole dipeptides having the three chemical structural formulas (A to C) shown in Figure 1, and obtained the following findings (a) to (c). (a) Cyclic imidazole dipeptides have stronger hydrophobicity (in other words, higher hydrophobicity) than known linear imidazole dipeptides. (b) Among the cyclic imidazole dipeptides, the hydrophobicity of cyclic balenine is the strongest, followed by that of cyclic anserine. Therefore, the hydrophobicity of cyclic carnosine is the weakest among the cyclic imidazole dipeptides. (c) The stronger the hydrophobicity, the longer it tends to remain in the blood after being absorbed into the blood. Therefore, for example, when an oral composition contains at least one cyclic imidazole dipeptide selected from the group consisting of cyclic balenine and cyclic anserine, it can be absorbed into the human body and remain in the blood for a longer period of time.

[0015] Furthermore, through repeated research and analysis into the effects on humans of the above-mentioned functionality, as well as physiological or medical actions, efficacy and effects, the inventors have come to gain new insight into the mixing ratio of cyclic imidazole dipeptides and known linear imidazole dipeptides when taken orally.

[0016] The present invention was created based on the above-mentioned various findings.

[0017] One oral composition of the present invention comprises a cyclic imidazole dipeptide and a linear imidazole dipeptide.

[0018] As described above, this oral composition contains, in addition to the linear imidazole dipeptide, a cyclic imidazole dipeptide having a higher hydrophobicity than the linear imidazole dipeptide, and therefore can promote effective absorption by humans of the imidazole dipeptide, which can exert physiological or medical effects, such as antioxidant and / or anti-fatigue effects, in the human body.

[0019] In the oral composition of the above-mentioned invention, when the sum of the first mole number of linear imidazole dipeptide per unit mass (mol (also referred to as "mole"; the same applies hereinafter) / g (also referred to as "gram"; the same applies hereinafter)) and the second mole number of cyclic imidazole dipeptide per unit mass (mol / g) is taken as 1, the second mole number being more than 0.01 (preferably more than 0.05, more preferably 0.1 or more, even more preferably 0.2 or more, and even more preferably 0.25 or more), the imidazole dipeptide can be present in human blood for a longer period of time, and therefore the effect on humans can last for a longer period of time.

[0020] Furthermore, one method for producing a food product of the present invention includes an injection step of injecting a solution or extract containing a cyclic imidazole dipeptide and a linear imidazole dipeptide into a food product, or an immersion step of immersing the food product in the solution or extract.

[0021] According to this food manufacturing method, at least the cyclic imidazole dipeptide is contained in the food through the above-mentioned injection step or soaking step, making it possible for humans to ingest more cyclic imidazole dipeptide than ever before.

[0022] Furthermore, one method for producing a beverage of the present invention includes a step of adding, mixing or dispersing a solution or extract containing a cyclic imidazole dipeptide and a linear imidazole dipeptide into a beverage.

[0023] According to this method for producing a beverage, at least the cyclic imidazole dipeptide is contained in the beverage through the above-mentioned adding, mixing or dispersing steps, making it possible for humans to ingest more cyclic imidazole dipeptide than ever before. Effect of the Invention

[0024] According to one oral composition of the present invention, in addition to a linear imidazole dipeptide, a cyclic imidazole dipeptide having a higher hydrophobicity than the linear imidazole dipeptide is contained, and therefore effective absorption by humans of the imidazole dipeptide, which can exert physiological or medical effects in the human body, such as antioxidant effects and / or anti-fatigue effects, can be promoted.

[0025] Furthermore, one of the food production methods or beverage production methods of the present invention enables humans to ingest more cyclic imidazole dipeptides than ever before. [Brief description of the drawings]

[0026] [Figure 1] 1 shows the chemical structural formulas of three types of cyclic imidazole dipeptides according to the first embodiment. (A: cyclic carnosine, B: cyclic anserine, C: cyclic balenine) [Diagram 2] These are the chemical structures of three known linear imidazole dipeptides. (A': linear carnosine, B': linear anserine, C': linear balenine) [Diagram 3] 1 is a table showing the contents of cyclic imidazole dipeptides and linear imidazole dipeptides detected in extracts of specific raw and processed products in the first embodiment. [Figure 4] 1 is a flow chart showing a production process of an oral composition according to a first embodiment, and various food and beverage products containing the oral composition. [Diagram 5] 4 is a flow chart showing the production process of another oral composition of the modified example (1) of the first embodiment, and various food and beverage products containing the oral composition. [Figure 6]1 shows the results of an analysis of the chemical structure of imidazole dipeptide in the meat of one individual of an ocean sunfish according to the modified example (1) of the first embodiment, using a liquid chromatography mass spectrometer. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0027] As an embodiment of the present invention, an oral composition containing a cyclic imidazole dipeptide and a linear imidazole dipeptide and a method for producing the same will be described in detail with reference to the accompanying drawings.

[0028] <First embodiment> Figure 1 shows the chemical structural formulas of three types of cyclic imidazole dipeptides of this embodiment. Note that A in Figure 1 is cyclic carnosine, B in Figure 1 is cyclic anserine, and C in Figure 1 is cyclic balenine.

[0029] <Analysis of imidazole dipeptides in unprocessed and processed foods> First, the inventor analyzed the chemical structures and functionality of imidazole dipeptides of processed products that have been subjected to only primitive processing such as fillets and sashimi (in this embodiment, for the sake of convenience, these will be referred to as "unprocessed products") and processed products that have been subjected to processing other than such primitive processing (heating, freezing, and / or drying, etc.) (in this embodiment, for the sake of convenience, these will be referred to as "processed products").

[0030] In this embodiment, the above-mentioned raw or processed pieces were dispersed in water at room temperature (about 25°C) and dissolved so that the dissolved material from the pieces was sufficiently contained in the water to prepare a solution, to which was added ethanol (purity 99.5 wt%) in an amount three times that of the solution at room temperature (about 25°C).Then, the supernatant of the solution was collected to prepare an extract as a sample for analysis.

[0031] The inventor then analyzed the chemical structures of the imidazole dipeptides in the samples prepared from the above-mentioned unprocessed products and the above-mentioned processed products using a liquid chromatograph mass spectrometer (manufactured by Shimadzu Corporation, model: LC-20, LCMS-2020).

[0032] FIG. 3 is a table showing the contents of cyclic imidazole dipeptides and / or linear imidazole dipeptides detected in the samples of the above-mentioned unprocessed products and processed products in this embodiment. In addition, "μmol" in the table is 10 -6 The "-" in the table indicates that neither linear imidazole dipeptide nor cyclic imidazole dipeptide was detected. Among the various samples shown in Figure 3, the unprocessed "raw chicken breast meat" and the processed "bonito flakes" and "chicken stock powder" were commercially available products.

[0033] As a result of analysis using the above-mentioned analytical device, it was confirmed that the chemical structural formulas of three types of cyclic imidazole dipeptides shown in Figure 1 could be identified from several samples, in addition to the known linear imidazole dipeptides shown in Figure 2. The inventor is not aware of any prior application, academic presentation or paper report by another person in which the detection of cyclic imidazole dipeptides has been announced. Therefore, it can be said that the above-mentioned analytical results open the way for research into the unique functionality and unique physiological or medical actions, efficacy and effects of new types of imidazole dipeptides.

[0034] Looking at the content of the newly discovered cyclic imidazole dipeptide, linear imidazole dipeptides were detected in the sample analyzed from the unprocessed product "raw chicken breast meat," but no cyclic imidazole dipeptides were detected at all, as shown in Figure 3. Also, trace amounts of cyclic imidazole dipeptides (cyclic anserine) were detected in the samples analyzed from "dried bonito flakes" and "chicken stock base."

[0035] Therefore, taking into account the analytical results of the sample analyzed from the unprocessed product "raw chicken breast meat" and the sample analyzed from "chicken stock base", since at least a thermal treatment, i.e., a heating or cooling treatment, is performed in the manufacturing process of "chicken stock base", the hypothesis is valid that cyclic imidazole dipeptides can be produced from linear imidazole dipeptides by the thermal treatment. This hypothesis was confirmed to be correct by the manufacturing method of the oral composition described below.

[0036] On the other hand, when a sample was analyzed that was freeze-dried powder (processed product) produced by freeze-drying whale muscle through a heat-induced freeze-drying process, a relatively large amount of cyclic imidazole dipeptides was detected along with linear imidazole dipeptides. More specifically, the types of cyclic imidazole dipeptides detected were cyclic balenine and cyclic carnosine.

[0037] A more specific method for producing the above-mentioned freeze-dried powder, which is an example of a step of performing a thermal operation, is as follows. First, the object to be freeze-dried is frozen by cooling to -40°C or less, more preferably -50°C or less. Then, while the object is in a frozen state, a decompression treatment is performed to reduce the pressure (for example, to 100 Pa or less, more preferably to 50 Pa or less). As a result, a freeze-dried powder of the object can be produced.

[0038] Upon further detailed investigation of the above-mentioned freeze-dried powder, it became very interesting to find that the detection ratios of linear carnosine and linear balenine in the linear imidazole dipeptide were completely different from the detection ratios of cyclic carnosine and cyclic balenine in the cyclic imidazole dipeptide.

[0039] Specifically, the proportion of linear carnosine when linear balenine is taken as 1 is about 5% to about 60%, while the proportion of cyclic carnosine when cyclic balenine is taken as 1 is a small value of less than 0.1%. Therefore, the inventors have found that, based on the results shown in FIG. 3, cyclic balenine tends to be more easily produced than cyclic carnosine when undergoing various processing steps in the production of dry powder, or that cyclic balenine tends to remain without being decomposed even during the production process of freeze-dried powder.

[0040] Furthermore, as already mentioned, taking into consideration the fact that cyclic imidazole dipeptides were detected by the freeze-drying process, it can be said that carrying out a drying process (which may include a vacuum / reduced pressure drying process and a concentration process by drying) together with or instead of the freezing process may contribute to the production of cyclic imidazole dipeptides, although the mechanism is not yet clear.

[0041] An example of a suitable processing condition for the above-mentioned freezing step is a freezing treatment for 30 minutes or more (more narrowly, 1 hour or more, even more narrowly, 2 hours or more, and even more narrowly, 4 hours or more) at -80° C. or more and -20° C. or less. An example of a suitable processing condition for the above-mentioned drying step is a treatment for a time sufficient for drying under conditions where the pressure in the drying chamber is 610 Pa or less (more preferably, 300 Pa or less, and even more preferably, 100 Pa or less).

[0042] Although not shown in Figure 3, the deep-sea fish Sunfish (also called "mandai") contains extremely abundant imidazole dipeptides, especially balenine. Heat-treated parts of the sunfish, including the ordinary muscle, at 90°C or higher, as well as their extracts (also heat-treated at 90°C or higher) and freeze-dried powders, contain cyclic imidazole dipeptides (especially cyclic balenine and cyclic carnosine), just like freeze-dried powder of whale meat.

[0043] <Method of producing oral composition> Next, a method for producing the oral composition of this embodiment will be described.

[0044] In this embodiment, a solution or extract produced through the same process as the sample extracted from the processed product shown in Fig. 3 is used, taking into account the analysis results shown in Fig. 3. Specifically, an oral composition is produced by carrying out a step of providing the extract containing cyclic imidazole dipeptides to the solution or extract containing no cyclic imidazole dipeptides or having a low content of cyclic imidazole dipeptides, or to an unprocessed product or a processed product.

[0045] FIG. 4 is a flow chart showing the production process of one oral composition of the present embodiment and various food and beverage products containing the oral composition.

[0046] In the method for producing an oral composition of this embodiment, each of the process steps shown in FIG. 4 and FIG. 5 described later may be all or a part of the process steps in the method for producing an oral composition. In addition, each of the process steps shown in the dotted line frame in FIG. 4 or FIG. 5 does not necessarily have to be performed. Therefore, the method for producing an oral composition of this embodiment does not necessarily have to include all of the process steps shown in FIG. 4 or FIG. 5.

[0047] An example of the oral composition in this embodiment is an extract containing cyclic imidazole dipeptide together with linear imidazole dipeptide. In this example, as described above, a solution (hereinafter also referred to as "first aqueous solution") in which the material dissolved from the processed product (containing cyclic imidazole dipeptide) is sufficiently contained in the water is prepared by dispersing the processed product pieces containing cyclic imidazole dipeptide in water, and then the supernatant of the solution obtained by adding ethanol is an extract, which is a primitive example of an oral composition.

[0048] For example, if raw chicken breast meat is used as the processing target, after receiving (including purchasing and receiving) the "raw chicken breast meat" from the supplier (Step S a1), an injection step of injecting the above-mentioned extract containing cyclic imidazole dipeptide or the above-mentioned first aqueous solution into the raw chicken breast meat using, for example, a plurality of injection needles (however, in this embodiment, a single injection needle may also be applied) disclosed in Japanese Patent No. 6360928, and / or an immersion step of immersing the raw chicken breast meat in the first aqueous solution or the extract (step S a By carrying out 2), the cyclic imidazole dipeptide can be contained in the raw chicken breast meat, in other words, the raw chicken breast meat can be fed.

[0049] As a result, meat or meat products containing cyclic imidazole dipeptides can be produced even if they are unprocessed products, without heat treatment. After that, the meat or meat products are packaged and shipped from the manufacturer of the meat or meat products to retailers, etc. (Step S a 3).

[0050] In this embodiment, the above-mentioned injection step and / or immersion step (step S a The raw chicken breast meat produced by the process of 2) itself has an aspect of being a "food" or "ingredient" and can also play a role as an "oral composition". That is, the "oral composition" in this embodiment does not simply mean a mixture of linear imidazole dipeptide and cyclic imidazole dipeptide as chemical substances.

[0051] In addition, the extract containing the above-mentioned cyclic imidazole dipeptide has been described as an example of an oral composition, but for example, the mixture shown in the following examples (p) and (q) is also another example of an oral composition of this embodiment. (p) A mixture of the first aqueous solution made from the above-mentioned "raw chicken breast meat" and an extract containing cyclic imidazole dipeptides made from a certain type of processed product (e.g., bonito flakes) (q) A mixture of an extract containing cyclic imidazole dipeptides derived from one type of processed product (e.g., dried bonito flakes) and an extract containing cyclic imidazole dipeptides derived from another type of processed product (e.g., freeze-dried powder of Bryde's whale muscle)

[0052] In addition, similarly to raw chicken breast meat, the above-mentioned injection step and / or soaking step (step S) may also be performed on processed products with a low content of cyclic imidazole dipeptides (e.g., dried bonito flakes, or dried bonito flakes that have not yet been smoked and have been boiled in hot water in the process of producing the dried bonito flakes). a By going through a process similar to that of 2), a processed product (e.g., dried bonito flakes) containing a larger amount of cyclic imidazole dipeptide can be produced.

[0053] In addition, in the same manner as with raw chicken breast meat, for example, unprocessed fish (sea bream, bonito, tuna, yellowtail, horse mackerel, pacific saury, salmon, sardine, mackerel, flounder, etc.) or seafood (shrimp, crab, scallop, shellfish, etc.) that have been landed can be subjected to the above-mentioned injection step and / or immersion step without being heat-treated, which is another aspect of this embodiment. By subjecting such fish or seafood to each step, humans can ingest more cyclic imidazole dipeptide than ever before, even in cooked products (fish meat, processed fish meat products) such as sashimi or carpaccio that do not require heat treatment.

[0054] As described above, by including an injection step of injecting the above-mentioned first aqueous solution containing a cyclic imidazole dipeptide and a linear imidazole dipeptide or the above-mentioned extract into various foods, or an immersion step of immersing the foods in the first aqueous solution or the extract, humans can ingest more cyclic imidazole dipeptide than ever before.

[0055] In addition, for example, a suitable embodiment that can be adopted is that the beverage contains the extract or the first aqueous solution of this embodiment by carrying out an addition step of adding the extract or the first aqueous solution described above to a known beverage (drinking water, functional beverage, sports beverage, tea (including green tea, black tea, oolong tea, and Chinese tea), fruit juice beverage, soft drink, carbonated beverage, milk, dairy beverage, soy milk, coffee, alcoholic beverage, etc.), a mixing step of mixing, or a dispersion step of dispersing, etc. The beverage described above that has been subjected to the addition step, mixing step, or dispersion step contains the extract (oral composition) or the first aqueous solution of this embodiment, making it possible for humans to ingest more cyclic imidazole dipeptide than ever before.

[0056] For example, in the oral composition of this embodiment, the above-mentioned step S a By carrying out a step similar to that of 2, an oral composition (e.g., a food or beverage) containing a cyclic imidazole dipeptide can be produced such that, when the sum of the first mole number (mol / g) of the linear imidazole dipeptide per unit mass and the second mole number (mol / g) of the cyclic imidazole dipeptide per unit mass is taken as 1, the second mole number is greater than 0.01 (preferably greater than 0.05, more preferably 0.1 or more, even more preferably 0.2 or more, even more preferably 0.25 or more, even more preferably 0.35 or more, and even more preferably 0.4 or more).

[0057] As described in this embodiment, even if the cyclic imidazole dipeptide is not detected by the above-mentioned analysis in a non-thermally manipulated composition (for oral use), foodstuff, or food or beverage, the composition, foodstuff, or food or beverage containing a cyclic imidazole dipeptide satisfying the following conditions is a preferred embodiment, since it enables humans to ingest more cyclic imidazole dipeptide than ever before. As a more specific example, from the above-mentioned viewpoint, the composition, foodstuff, or food or beverage containing a cyclic imidazole dipeptide satisfying the following conditions even when stored at room temperature, in other words, when not heated to 45°C or higher (more narrowly, 40°C or higher, and even more narrowly, 35°C or higher). [conditions] When the sum of the first mole number (mol / g) of the linear imidazole dipeptide per unit mass and the second mole number (mol / g) of the cyclic imidazole dipeptide per unit mass is taken as 1, the second mole number is greater than 0.01 (preferably greater than 0.05, more preferably 0.1 or more, even more preferably 0.2 or more, even more preferably 0.25 or more, even more preferably 0.35 or more, and even more preferably 0.4 or more).

[0058] In another preferred embodiment, the oral composition of this embodiment, and food and beverage products including meat, processed meat products, fish meat, processed fish meat products, and beverages contain linear imidazole dipeptides and cyclic imidazole dipeptides, and thus the oral composition and the food and beverage products can be used for one or more applications selected from the group consisting of the following (1) to (8): (1) Suppression of blood pressure rise in humans (2) Suppression of increases in neutral fat levels in human blood (3) Suppression of cognitive decline in humans (4) Improving human sleep quality (5) Reducing human stress (6) Suppression of increases in uric acid levels in humans (7) Improving human antioxidant capacity (8) Improve anti-fatigue ability in humans

[0059] In other words, the oral composition or food or beverage of this embodiment is an oral composition or food or beverage that contains a linear imidazole dipeptide and a cyclic imidazole dipeptide and has one or more actions or efficacies selected from the group consisting of (1) to (8) above, or that can exhibit one or more of the characteristics or actions. In other words, this embodiment is the use of an oral composition or food or beverage that contains a linear imidazole dipeptide and a cyclic imidazole dipeptide and is for one or more of the actions or efficacies selected from the group consisting of (1) to (8) above.

[0060] In addition to the above-mentioned examples, examples of food and beverage products according to this embodiment include various processed foods, health foods, sweets, and the like.

[0061] Meanwhile, the oral composition of the present embodiment has a water content of more than 0 wt% and 10 wt% or less, that is, an oral composition with a reduced water content is another preferred embodiment. Specifically, this is because a so-called dry oral composition is more advantageous than the liquid oral composition of the present embodiment in the following respects. (x) Cyclic imidazole dipeptides may be more susceptible to spontaneous decomposition when kept in liquid form than linear imidazole dipeptides. (y) Cyclic imidazole dipeptides may be more susceptible to chemical changes when kept in liquid form than linear imidazole dipeptides. (z) When kept in liquid form, the hydrophobicity of cyclic imidazole dipeptides may be more easily changed than that of linear imidazole dipeptides.

[0062] In the present embodiment, in one example of a method for producing an oral composition having a water content of more than 0 wt% and not more than 10 wt%, a concentration step and a powdering step by spray drying can be adopted. For example, the first aqueous solution or the extract described above can be concentrated by heating (e.g., heating at several tens of degrees Celsius) in a space under reduced pressure (e.g., 0.03 MPa), and then the first aqueous solution or the extract can be dried and powdered by a known spray drying method to produce a powder having the above water content.

[0063] The moisture content of the powder obtained by the above-mentioned spray drying method can be adjusted by a known means as appropriate. However, in addition to the above-mentioned viewpoints, in consideration of the viewpoint of ease of transportation and / or ease of handling, it is a preferred embodiment that the moisture content is more than 0 wt% and 10 wt% or less of the powder of this embodiment. In addition, from the viewpoints of (x) to (z) above or the viewpoint of ease of transportation and / or ease of handling, the moisture content is more preferably 5 wt% or less of the powder of this embodiment, and even more preferably 3 wt% or less of the powder of this embodiment.

[0064] <Modification (1) of the First Embodiment> Another example of the oral composition in this modification is an aqueous solution or extract containing cyclic imidazole dipeptides, which is produced by subjecting an extract containing linear imidazole dipeptides to a treatment involving heat manipulation (e.g., heat treatment). Except for the treatment involving heat manipulation, this modification is the same as the first embodiment. Therefore, the description overlapping with the first embodiment may be omitted.

[0065] FIG. 5 is a flow chart showing the production process of another oral composition of the present modified example (1) and various food and beverage products containing the oral composition.

[0066] In the method for producing the oral composition in this modified example, similarly to the first embodiment, pieces of an unprocessed or processed product containing at least linear imidazole dipeptide are dispersed in water, and a solution is prepared so that the dissolved material (containing linear imidazole dipeptide) from the pieces is sufficiently contained in the water. The solution is then subjected to a predetermined treatment involving heat (e.g., a heating treatment) to produce a cyclic imidazole dipeptide from the linear imidazole dipeptide. b 2)) is included.

[0067] Specifically, the present inventors have repeatedly conducted trial and error to realize a process for producing cyclic imidazole dipeptides from linear imidazole dipeptides, and as a result, have found that by subjecting the solution to a heat treatment for 30 minutes or more (more preferably 1 hour or more, more preferably 2 hours or more, and even more preferably 4 hours or more) under conditions in which the set temperature of a heat treatment device (manufactured by Hirayama Manufacturing Co., Ltd., model HICLAVE HVE-25) is 90°C or higher (more preferably 110°C or higher, even more preferably 120°C or higher) and 200°C or lower, it is possible to produce cyclic imidazole dipeptides (cyclic carnosine, cyclic anserine, cyclic balenine) shown in Figure 1 from linear imidazole dipeptides (linear carnosine, linear anserine, linear balenine) shown in Figure 2. As a result, a solution containing cyclic imidazole dipeptides (hereinafter also referred to as "second aqueous solution") is obtained after the above-mentioned heat treatment. The upper and lower limits of the treatment time for the heat treatment are not particularly limited as long as the treatment time is within a range in which cyclic imidazole dipeptides can be produced from linear imidazole dipeptides.

[0068] In this modified example, ethanol is then added to the second aqueous solution to obtain an extract (supernatant of the solution) containing the cyclic imidazole dipeptide. The second aqueous solution and the extract are suitable examples of an oral composition.

[0069] Therefore, it is worth noting that even if the above-mentioned solution, which is obtained by merely dissolving a part of an unprocessed or processed product in water, does not contain cyclic imidazole dipeptide, a second aqueous solution containing cyclic imidazole dipeptide and the extract thereof (supernatant of a mixture of the second aqueous solution and an aqueous ethanol solution) can be produced by subjecting the solution to a treatment involving a specific thermal operation (e.g., a heat treatment).

[0070] For reference, an example is shown in which the difference between the case where the treatment involving the above-mentioned thermal operation is performed and the case where the treatment involving the thermal operation is not performed is confirmed.

[0071] First, as an example of a treatment involving the above-mentioned heat operation, an extract extracted from the flesh of a sunfish using water at about 20°C was heated at about 95°C, vacuum-dried at room temperature to form a powder, and then dissolved in water (the subject of the measurement). The results are shown below. The results are shown in Fig. 6, which shows the results of an analysis of the chemical structure of imidazole dipeptides using a liquid chromatograph mass spectrometer for the flesh of a certain sunfish. Note that Fig. 6(a) shows cyclic and chain-like carnosine, Fig. 6(b) shows cyclic and chain-like anserine, and Fig. 6(c) shows cyclic and chain-like balenine. The "standard" is a cyclic imidazole dipeptide that is artificially produced from linear imidazole dipeptide by heating at 120°C for 3 hours, and then the cyclic imidazole dipeptide is analyzed; it is used as a comparison object for the measurement subject.

[0072] As shown in Figure 6, cyclic imidazoles (particularly cyclic carnosine and cyclic balenine) were detected in the extract of the fish meat of the sunfish that had been heat-treated at about 95°C. Therefore, as already mentioned, it was confirmed that an extract (aqueous solution) containing cyclic imidazole dipeptides can be produced by subjecting an extract (aqueous solution) that does not contain cyclic imidazole dipeptides to a treatment involving a specific heat operation (for example, a heat treatment).

[0073] Next, as a comparative example that did not undergo the above-mentioned thermal processing, the flesh of the sunfish was subjected to only basic processing without heat treatment (in this example, fillets), and similarly analyzed using the liquid chromatography mass spectrometer. As a result, linear imidazole dipeptides were detected, but cyclic imidazoles (cyclic carnosine, cyclic anserine, and cyclic balenine) were not detected.

[0074] More specifically, when an extract of the flesh of the sunfish that had not been subjected to a thermal treatment (e.g., extracted from the flesh of the sunfish using water at about 20°C) was analyzed using the above-mentioned liquid chromatography mass spectrometer, cyclic imidazoles (cyclic carnosine, cyclic anserine, and cyclic balenine) were not detected. Therefore, as already described, it was confirmed that an extract (aqueous solution) containing cyclic imidazole dipeptides is not produced unless a treatment involving a predetermined thermal treatment (e.g., heat treatment) is performed on an extract (aqueous solution) that does not contain cyclic imidazole dipeptides. According to the analysis by the present inventor, the production of cyclic imidazole dipeptides is highly reliably suppressed by performing a processing treatment (including a primitive processing treatment and extraction treatment) at room temperature (in this application, 0°C to 40°C, more preferably 10°C to 35°C) without performing a heating treatment and / or a cooling treatment.

[0075] Therefore, as a result of research and analysis by the present inventors, when producing a cyclic imidazole dipeptide from a linear imidazole dipeptide by heat treatment, it is preferable that the set temperature of the heat treatment device is 90°C or higher (more preferably 110°C or higher, and even more preferably 120°C or higher) and 200°C or lower.

[0076] Thereafter, in the same manner as in the production flow described in FIG. 4, the above-mentioned extract containing cyclic imidazole dipeptide or the above-mentioned second aqueous solution is injected into, for example, raw chicken breast meat using one or more injection needles, and / or the raw chicken breast meat is immersed in the extraction part (step S b By carrying out 3), the cyclic imidazole dipeptide can be contained in the raw chicken breast meat, in other words, the raw chicken breast meat can be fed.

[0077] Similarly to raw chicken breast meat, a processed product with a low content of cyclic imidazole dipeptides (e.g., dried bonito flakes, or dried bonito flakes immediately after boiling in hot water before being smoked in the process of producing the same) can be subjected to the above-mentioned step involving heat manipulation (e.g., a heating step) and an injection step and / or a soaking step to produce a processed product (e.g., dried bonito flakes) that contains a higher amount of cyclic imidazole dipeptides.

[0078] In another aspect of this embodiment, similarly to raw chicken breast meat, for example, landed fish (sea bream, bonito, tuna, yellowtail, horse mackerel, pacific saury, salmon, sardine, mackerel, flounder, etc.) or seafood (shrimp, crab, scallop, shellfish, etc.) are subjected to the above-mentioned heating step for preparing the second aqueous solution and the extract, and the injection step and / or immersion step without a treatment involving heat manipulation (for example, heat treatment). By subjecting such fish or seafood to the above-mentioned steps, humans can ingest more cyclic imidazole dipeptide than ever before, even in cooked products (fish meat, processed fish meat products) such as sashimi or carpaccio that do not require heat treatment.

[0079] As described above, by including the heating step for preparing the second aqueous solution and the extract, and the injection step of injecting the second aqueous solution and the extract into various foods, or the soaking step of soaking the foods in the second aqueous solution or the extract, humans can ingest more cyclic imidazole dipeptides than ever before.

[0080] In addition, for example, a suitable embodiment that can be adopted is that the beverage contains the extract or the second aqueous solution of this embodiment by carrying out an addition step of adding the second aqueous solution or the extract, a mixing step of mixing, or a dispersion step of dispersing in a known beverage (drinking water, functional beverage, sports beverage, tea (including green tea, black tea, oolong tea, and Chinese tea), fruit juice beverage, soft drink, carbonated beverage, milk, dairy beverage, soy milk, coffee, alcoholic beverage, etc.). When the beverage described above that has been subjected to the addition step, mixing step, or dispersion step contains the extract or the second aqueous solution of this embodiment, i.e., the oral composition of this embodiment, humans can ingest more cyclic imidazole dipeptide than ever before.

[0081] Instead of the above-mentioned solution example described in this modified example, the second aqueous solution may be prepared by dissolving a part of a processed product containing a cyclic imidazole dipeptide. b The fact that the solution before carrying out 2) contains the cyclic imidazole dipeptide means that the cyclic imidazole dipeptide can be contained in the second aqueous solution or the extract after the heating step with a higher degree of certainty. Therefore, after the imidazole dipeptide, which can exert physiological or medical effects in the human body, such as antioxidant and / or anti-fatigue effects, is absorbed into human blood, the presence of the imidazole dipeptide in the blood for a long period of time can be realized with a higher degree of certainty.

[0082] In addition, the heating step (step S b The heating means used in 2) is not particularly limited as long as it can provide an amount of heat equivalent to that supplied by the heating step of this modified example. Typical heating means include heating by direct flame, heating using electromagnetic waves such as far infrared rays, or heating using an electric heating device.

[0083] In addition, as mentioned above, among the cyclic imidazole dipeptides, cyclic balenine has the strongest hydrophobicity, and cyclic anserine has the second strongest hydrophobicity, so that the cyclic imidazole dipeptide is at least one selected from the group consisting of cyclic balenine and cyclic anserine, and thus it can be more reliably realized that the cyclic imidazole dipeptide will remain in the blood for a longer period of time after being absorbed into the blood of a human. Therefore, the oral composition of this modification, as well as food and beverage products including meat, processed meat products, fish meat, processed fish meat products, and beverages, can be more reliably realized that the imidazole dipeptide will remain in the blood for a longer period of time after being absorbed into the blood of a human by including, for example, the second aqueous solution or the extract obtained from the freeze-dried powder of whale meat shown in FIG. 3.

[0084] Therefore, it is a preferred aspect that the oral composition of this modified example, and food and beverage products including meat, processed meat products, fish meat, processed fish meat products, and beverages, contain linear imidazole dipeptides and cyclic imidazole dipeptides, and thus the oral composition and the food and beverage products can be used for one or more applications selected from the group consisting of (1) to (8) described in the first embodiment.

[0085] In addition, based on the analysis results shown in Figure 3, the oral composition of this modification, as well as food and beverage products including meat, processed meat products, fish meat, processed fish meat products, and beverages, can more reliably realize the long-term presence of the imidazole dipeptide in human blood after absorption into the blood, and as a result, the effect of the imidazole dipeptide on humans can last for a longer period of time. Specifically, when the sum of the first mole number (mol / g) of the linear imidazole dipeptide per unit mass and the second mole number (mol / g) of the cyclic imidazole dipeptide per unit mass is 1, the second mole number being more than 0.01 (preferably more than 0.05, more preferably 0.1 or more, even more preferably 0.2 or more, even more preferably 0.25 or more, even more preferably 0.35 or more, even more preferably 0.4 or more) can more reliably realize the long-term presence of the imidazole dipeptide in human blood after the imidazole dipeptide is absorbed into the blood. Note that the upper limit of the value of the ratio of the second mole number described above is not limited as long as the action or effect of the cyclic imidazole dipeptide in this embodiment is not impaired.

[0086] Furthermore, similar to the oral composition of the first embodiment, the moisture content of the oral composition of this modified example is more than 0 wt% and not more than 10 wt%, i.e., the oral composition has a reduced moisture content, which is another preferred embodiment.

[0087] <Modification (2) of the First Embodiment> This modification is the same as the first embodiment, except that the supplement or formulation contains the extract and / or oral composition in the first embodiment and its modification (1) (hereinafter, in this modification, typically referred to as "oral composition"). Therefore, the description overlapping with the first embodiment may be omitted.

[0088] In this modification, the oral composition described in the first embodiment and its modification (1), or a powder of the oral composition with reduced water content, can be used as various supplements or various formulations.

[0089] Specifically, one suitable embodiment that can be adopted is to produce a supplement using the above-mentioned oral composition or a powder of the oral composition as a raw material or a part thereof, using a known production method (e.g., a known granulation method, a known tableting method, a known dissolution and filtration method, etc.).

[0090] In addition, one suitable embodiment that can be adopted is to produce the following (a) and / or (b) using the above-mentioned oral composition or a powder of the oral composition as a raw material or a part thereof, using a known production method (e.g., a known granulation method, a known tabletting method, a known dissolution and filtration method, a known spreading method, etc.). (a) The oral composition described above, or a powder of the oral composition, which contains at least a portion of its components, such as tablets, capsules, powders (including granules), film preparations, pills, syrups (including dry syrups), liquids, drinks, lozenges, drops, starch syrups, etc. (hereinafter collectively referred to as "preparations"). (b) The preparation, which contains, as at least a part of its components, the oral composition described above, or a solution in which a powder of the oral composition is dissolved in a physiologically acceptable liquid medium, or a gel formed from the powder.

[0091] In addition, the above-mentioned supplement or the above-mentioned formulation may be formed by mixing a disintegrant or wetting agent, or honey, etc., as appropriate, in addition to a known excipient or binder, in order to improve moldability or ease of oral ingestion or administration.

[0092] Since the supplement or formulation of this variation contains an imidazole dipeptide, particularly a cyclic imidazole dipeptide, when ingested by a human, the supplement or formulation may have, for example, one or more effects selected from the group consisting of at least the following (1) to (8). (1) Suppression of blood pressure rise in humans (2) Suppression of increases in neutral fat levels in human blood (3) Suppression of cognitive decline in humans (4) Improving human sleep quality (5) Reducing human stress (6) Suppression of increases in uric acid levels in humans (7) Improving human antioxidant capacity (8) Improve anti-fatigue ability in humans

[0093] <Modification (3) of the First Embodiment> This modification is the same as the first embodiment, except that the cosmetic contains the extract and / or oral composition in the first embodiment and its modification (1) (hereinafter, in this modification, typically referred to as the "oral composition"). Therefore, the description overlapping with the first embodiment may be omitted.

[0094] In this modification, the oral composition described in the first embodiment and its modification (1), or a powder of the oral composition with a reduced water content, can be used as various types of cosmetics.

[0095] Specifically, one suitable embodiment that can be adopted is to produce various types of cosmetics using the above-mentioned oral composition or a powder of the oral composition as a raw material or a part thereof, using a known manufacturing method (e.g., a known granulation method, a known tableting method, a known dissolution and filtration method, etc.).

[0096] The various foods, beverages, cosmetics, supplements, and preparations described in the first embodiment and its modified examples (1) to (3) can also be described as follows, without using the term oral composition. (i) containing a cyclic imidazole dipeptide and a linear imidazole dipeptide; and A food or beverage product, in which when the sum of a first number of moles (mol / g) of the linear imidazole dipeptide per unit mass and a second number of moles (mol / g) of the cyclic imidazole dipeptide per unit mass is taken as 1, the second number of moles is greater than 0.01. (ii) containing a cyclic imidazole dipeptide and a linear imidazole dipeptide; and A cosmetic product, in which, when the sum of a first number of moles (mol / g) of the linear imidazole dipeptide per unit mass and a second number of moles (mol / g) of the cyclic imidazole dipeptide per unit mass is taken as 1, the second number of moles is more than 0.01. (iii) containing a cyclic imidazole dipeptide and a linear imidazole dipeptide; and A supplement in which, when the sum of a first number of moles (moles / g) of the linear imidazole dipeptide per unit mass and a second number of moles (moles / g) of the cyclic imidazole dipeptide per unit mass is taken as 1, the second number of moles is greater than 0.01. (iv) containing a cyclic imidazole dipeptide and a linear imidazole dipeptide; and A formulation, in which when the sum of a first number of moles (mol / g) of the linear imidazole dipeptide per unit mass and a second number of moles (mol / g) of the cyclic imidazole dipeptide per unit mass is taken as 1, the second number of moles is more than 0.01.

[0097] The disclosure of the above-mentioned embodiments and their modifications is provided for the purpose of explaining the embodiments and their modifications, and is not provided for the purpose of limiting the present invention. In addition, modifications within the scope of the present invention, including other combinations of the embodiments, are also included in the scope of the claims. [Industrial Applicability]

[0098] One oral composition of the present invention can contain a cyclic imidazole dipeptide that enhances human physiological functions, and is therefore extremely useful not only in the food and fisheries industries, but also in industries related to medicine, health, medical care, and beauty.

Claims

1. Contains a cyclic imidazole dipeptide and a linear imidazole dipeptide, and When the sum of a first mole number (mol / g) of the linear imidazole dipeptide per unit mass and a second mole number (mol / g) of the cyclic imidazole dipeptide per unit mass is taken as 1, the second mole number is more than 0.

01. Oral compositions.

2. the sum of the first mole number (mol / g) of the linear imidazole dipeptide per unit mass and the second mole number (mol / g) of the cyclic imidazole dipeptide per unit mass is 1, the second mole number is 0.2 or more; The oral composition of claim 1.

3. the sum of the first mole number (mol / g) of the linear imidazole dipeptide per unit mass and the second mole number (mol / g) of the cyclic imidazole dipeptide per unit mass is 1, the second mole number is 0.25 or more; The oral composition of claim 1.

4. The oral composition is not thermally engineered, When the sum of the first mole number (mol / g) of the linear imidazole dipeptide per unit mass and the second mole number (mol / g) of the cyclic imidazole dipeptide per unit mass is taken as 1, the second mole number is more than 0.

01. The oral composition of claim 1.

5. The cyclic imidazole dipeptide is at least one selected from the group consisting of cyclic balenine and cyclic anserine. The oral composition according to any one of claims 1 to 4.

6. The moisture content is more than 0 wt% and 10 wt% or less. The oral composition according to any one of claims 1 to 4.

7. The oral composition according to any one of claims 1 to 4, Food and beverages.

8. The oral composition according to any one of claims 1 to 4, cosmetics.

9. The oral composition according to any one of claims 1 to 4, supplement.

10. The oral composition according to any one of claims 1 to 4, formulation.

11. The method includes an injection step of injecting a solution or extract containing a cyclic imidazole dipeptide and a linear imidazole dipeptide into a food product, or an immersion step of immersing the food product in the solution or the extract. Food production methods.

12. The method includes adding, mixing or dispersing a solution or extract containing a cyclic imidazole dipeptide and a linear imidazole dipeptide into a beverage. A method for producing a beverage.

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