Composition for preventing or improving aging-related hearing loss

Abstract

The present disclosure addresses the problem of providing technology for preventing or improving aging-related hearing loss. This problem is solved by a composition for preventing or improving aging-related hearing loss, the composition comprising, as an active ingredient, at least one selected from the group consisting of spirulina, phycocyanin, and phycocyanobilin.

Description

Composition for preventing or improving presbycusis

[0001] The present disclosure relates to a composition for preventing or improving presbycusis.

[0002] Presbycusis is a sensorineural hearing loss, and it is known that the decline of the function of peripheral sensory organs, the decline of the function of the auditory center, and the decline of overall cognitive function are involved (Non-Patent Document 1). As an active ingredient of a composition for preventing or improving presbycusis, for example, nicotinamide mononucleotide (NMN) (Patent Document 1), a prescription containing all of Atractylodes macrocephala (Biyakujutsu), Poria cocos (Bukuryo), Cinnamon (Keihi), and Licorice (Kanzou), or extracts thereof (Patent Document 2), etc. are known.

[0003] On the other hand, an alga called Spirulina is known (Patent Document 3). As an application of Spirulina, for example, prevention or treatment of non-alcoholic steatohepatitis is known (Patent Document 4).

[0004] Also, a pigment protein called phycocyanin contained in Spirulina is known. As an application of phycocyanin, for example, increase and suppression of decrease in muscle mass, increase in muscle mass and suppression of muscle atrophy are known (Patent Document 3).

[0005] Further, phycocyanin contained in Spirulina is known to have phycocyanobilin as a chromophore. As an application of phycocyanobilin, for example, anti-inflammation and antioxidant effects are known (Non-Patent Document 2).

[0006] JP-A-2023-154540 JP-A-2023-031386 WO2022 / 158503 JP-A-2009-256230

[0007] Yumi Ohta, "Clinical pathology and management of presbyacusis," Japanese Journal of Geriatrics, 2020; 57: 397-404. "Successful development of a high-speed extraction method for the natural blue chromophore phycocyanobilin," Toyohashi University of Technology Press Release, [online], January 6, 2021, [Retrieved April 12, 2024], Internet <URL: https: / / www.tut.ac.jp / docs / PR210106.pdf>

[0008] The issue addressed in this disclosure is to provide technologies for preventing or improving age-related hearing loss.

[0009] The present inventors have diligently studied to solve the above problems and have found that at least one selected from the group consisting of spirulina, phycocyanin, and phycocyanobilin can solve the above problems. This disclosure can provide the following.

[0010] <1> A composition for preventing or improving age-related hearing loss, comprising at least one selected from the group consisting of spirulina, phycocyanin, and phycocyanobilin as an active ingredient. <2> The composition according to <1>, wherein the age-related hearing loss is hearing loss in the frequency range of 12 kHz to 36 kHz. <3> The composition according to <2>, wherein the age-related hearing loss is age-related hearing loss in a subject aged 20 weeks or older, equivalent to the age of an aging-accelerated model mouse. <4> The composition according to <1>, comprising spirulina as an active ingredient, wherein the age-related hearing loss is hearing loss in the frequency range of 4 kHz to 12 kHz. <5> The composition according to <4>, wherein the age-related hearing loss is age-related hearing loss in a subject aged 28 weeks or older, equivalent to the age of an aging-accelerated model mouse. <6> The composition according to <1>, wherein the subject is male and the age-related hearing loss is hearing loss in the frequency range of 4 kHz to 12 kHz. <7> The composition according to <6>, wherein the age-related hearing loss is age-related hearing loss in a subject that is between 36 weeks of age and 48 weeks of age in C57BL / 6J mice. <8> The composition according to <1>, wherein the subject is male and the age-related hearing loss is hearing loss in the frequency range of 12 kHz to 36 kHz. <9> The composition according to <8>, wherein the age-related hearing loss is age-related hearing loss in a subject that is 38 weeks of age or older in C57BL / 6J mice. <10> The composition according to any one of <1> to <9>, which is a food or beverage composition. <11> The composition according to any one of <1> to <9>, which is a pharmaceutical composition. <12> A feed composition, which is one of the compositions described in <1> to <9>.

[0011] This disclosure provides a technology for preventing or improving age-related hearing loss.

[0012] In this disclosure, the technical features described may be combined as appropriate.

[0013] In this disclosure, "X to Y" indicating a range means "X or greater and Y or less". Furthermore, when numerical ranges expressed as "X to Y" or "X or greater and Y or less" are listed in steps (for example, in preferred order), the upper and lower limits of each numerical range can be any combination. In this disclosure, a statement such as "one or more selected from the group consisting of X, Y, and Z" means any of X, Y, Z, a combination of X and Y, a combination of X and Z, a combination of Y and Z, or a combination of X, Y, and Z. In this disclosure, a statement such as "X such as x1, x2, and x3" is given as an example of X, and does not mean that X is limited to x1, x2, and x3.

[0014] In this disclosure, terms such as "ingestion," "ingestion," and "ingested" may be replaced with terms such as "administration," "being administered," and "administered," respectively. Terms such as "administration," "being administered," and "administered" may be used, for example, in reference to feed compositions and pharmaceutical compositions.

[0015] One aspect of this disclosure is a composition for preventing or improving age-related hearing loss, comprising at least one selected from the group consisting of spirulina, phycocyanin, and phycocyanobilin as an active ingredient.

[0016] In this embodiment, Spirulina refers to an alga of the genus Arthrospira in the order Oscillarianes of the class Cyanobacteria, and contains abundant proteins, sugars, various vitamins, minerals, and plant pigments. Although Spirulina belongs to the genus Arthrospira, it is common to refer to the genus Arthrospira as Spirulina, so in this disclosure, it may be referred to as the genus Spirulina. Therefore, Spirulina may be read as Arthrospira.

[0017] Examples of spirulina in this embodiment include Spirulina platensis, Spirulina maxima, Spirulina geitleri, Spirulina siamese, Spirulina major, Spirulina subsalasa, Spirulina princeps, Spirulina laxissima, Spirulina curta, and Spirulina spirulinoides. Among these, Spirulina platensis, Spirulina geitleri, and Spirulina siamese are particularly desirable because they can be easily obtained and cultured artificially.

[0018] Examples of phycocyanin in this embodiment include phycocyanin derived from algae. Specifically, examples include phycocyanin derived from cyanobacteria, phycocyanin derived from red algae, phycocyanin derived from cryptophytes, and one or more of these may be used. Among these, phycocyanin derived from cyanobacteria is preferred because it can be collected in large quantities.

[0019] Examples of cyanobacteria include those belonging to the genera Arthrospira (Spirulina), Aphanizomenon, Fisherella, Anabaena, Nostoc, Synechocystis, Synechococcus, Tolypothrix, Aphanothece, Mastigoclaus, and Pleurocapsa, and one or more of these may be used. Among these, cyanobacteria of the genus Spirulina are preferred, as are cyanobacteria of the genus Arthrospira, which are produced on an industrial scale and whose safety has been confirmed. Furthermore, cyanobacteria of the genus Spirulina are more preferred. In addition, fresh algal bodies may be used, dried algal bodies may be used, one or the other may be used, or both may be used. As for the dried algal bodies, dried fresh algal bodies prepared by conventional methods may be used, commercially available dried products may be used, one or the other may be used, or both may be used.

[0020] Examples of phycocyanins include C-phycocyanin, R-phycocyanin, and allophycocyanin, and one or more of these may be used. From the viewpoint of quality, safety, and availability, C-phycocyanin is preferred. Furthermore, an embodiment containing both C-phycocyanin and allophycocyanin is also preferred.

[0021] Any known and conventional method can be used for extracting phycocyanin without particular restrictions. For example, phycocyanin can be extracted after its cell walls have been broken down by drying, or after its cell walls have been broken down by freezing and thawing, and then extracted with a solvent in which phycocyanin dissolves, such as water, buffer solution, or alcohol. Alternatively, methods for extracting phycocyanin described in International Publication No. 2013 / 105430 (International Application No.: PCT / JP2012 / 083471) or Japanese Patent Publication No. 2022-513061 may be used.

[0022] Furthermore, in order to extract high-purity phycocyanin, it is preferable to remove impurities from spirulina. Specifically, the extraction method described in extraction method (i) below is an example. High-purity phycocyanin with a vivid color can be obtained by extraction method (i) below.

[0023] <<Method for extracting phycocyanin (i)>> The extraction method (i) includes: a first step of obtaining an extract by extracting phycocyanin from cyanobacteria into an aqueous suspension; a second step of reacting a calcium salt and a phosphate in the extract to produce calcium phosphate and adsorbing impurities of phycocyanin onto the calcium phosphate to obtain adsorbent material; and a third step of removing cyanobacteria residue and adsorbent material from the extract.

[0024] Furthermore, it is more preferable that the above extraction method (i) is the following extraction method (ii). <<Extraction method for phycocyanin (ii)>> Extraction method (ii) includes: a first step of obtaining an extract by extracting phycocyanin from cyanobacteria into an aqueous suspension; a second step of reacting a calcium salt and a phosphate in the extract to produce calcium phosphate and adsorbing impurities of phycocyanin onto the calcium phosphate to obtain adsorbent material; a third step of removing cyanobacteria residue and adsorbent material from the extract; and a step of adding a chelating agent to the extract before the third step.

[0025] By using the above phycocyanin extraction method (i) or (ii), high-quality phycocyanin can be extracted from cyanobacteria. In particular, by using the above extraction method (i) or (ii) for cyanobacteria of the genus Spirulina, high-quality phycocyanin with a good mixing ratio of C-phycocyanin to allophycocyanin can be extracted. In the above extraction method, it is preferable to adjust the mixing ratio of C-phycocyanin to allophycocyanin to a desired range by appropriately selecting the extraction conditions.

[0026] The type of phycocyanin may be entirely C-phycocyanin. Alternatively, allophycocyanin may be included, or a mixture of C-phycocyanin and allophycocyanin may be included in the composition. The mixing ratio of C-phycocyanin to allophycocyanin is preferably 3 to 9.5:0.5 to 7 by mass ratio, more preferably 6 to 9.5:0.5 to 4, and even more preferably 7 to 8:2 to 3.

[0027] The phycocyanobilin used in this embodiment is a natural blue chromophore found in cyanobacteria. The phycocyanobilin used in this embodiment may be obtained by conventional methods. For example, phycocyanin powder may be suspended in an ethanol solution, heat-extracted, the ethanol removed from the extract, and dried by freeze-drying or the like. More specific examples include the preparation examples described in the examples below.

[0028] The composition of this embodiment may contain the active ingredient alone, or it may contain other ingredients that, when in compositional form, exert an effect of preventing or improving age-related hearing loss. If the composition of this embodiment contains such other ingredients, the composition of this embodiment may be a mixture of the active ingredient and the other ingredients, and these ingredients may be uniform or heterogeneous.

[0029] Mammals are examples of animals that may ingest the composition of this embodiment. Mammals include humans and non-human mammals. Examples of non-human mammals include pets and livestock, and more specifically, cattle, horses, goats, sheep, pigs, monkeys, dogs, cats, rats, mice (e.g., aging-accelerated model mice (e.g., SAMP8 aging-accelerated model mice), C57BL / 6J mice, etc.), hamsters, guinea pigs, etc. The sex may be male (male in the case of humans) or female (female in the case of humans). In this disclosure, the word "person" is sometimes used, for example, "healthy person," assuming the subject is human, but if the subject is not human, it may be read as equivalent to "person".

[0030] The composition of this embodiment has the effect of preventing or improving age-related hearing loss. Therefore, the composition of this embodiment can be used to prevent or improve age-related hearing loss. "Improvement of age-related hearing loss" may mean an improvement in age-related hearing loss, or it may mean preventing or delaying the worsening (or progression) of age-related hearing loss. When the composition of this embodiment is used for therapeutic purposes, "improvement" may mean "treatment".

[0031] The composition of this embodiment may be used for non-therapeutic purposes or for therapeutic purposes. "Non-therapeutic purposes" refers to purposes that do not involve medical procedures. In other words, purposes that do not involve treatment of the subject. Examples include uses for maintaining or promoting health.

[0032] When the composition of this embodiment is used for non-therapeutic purposes, it may be intended for healthy individuals. A "healthy individual" is defined as a person who does not have age-related hearing loss (not a patient with age-related hearing loss) at the time of ingesting the composition of this embodiment, and may include individuals who are concerned about age-related hearing loss, or who are prone to age-related hearing loss. When the composition of this embodiment is used for non-therapeutic purposes, it may be used to prevent or improve age-related hearing loss in healthy individuals.

[0033] When the composition of this embodiment is used for therapeutic purposes, it may be used in non-healthy individuals. "Non-healthy individuals" may refer to individuals who, at the time of ingesting the composition of this embodiment, are diagnosed with age-related hearing loss (patients with age-related hearing loss), etc. When the composition of this embodiment is used for therapeutic purposes, improvement (treatment) of age-related hearing loss may be achieved in non-healthy individuals.

[0034] Furthermore, symptoms that appear with age-related hearing loss may be divided into "symptoms caused by age-related hearing loss" and "symptoms caused by factors other than age-related hearing loss." For example, in the case of food and beverage compositions or health foods, they may be for "symptoms caused by factors other than age-related hearing loss" and may be targeted at healthy individuals.

[0035] Furthermore, the effect on "age-related hearing loss" in health foods and beverages may be described as "helping to maintain hearing at a healthy level," or "helping to maintain hearing at a level comparable to that of a healthy person."

[0036] This disclosure can provide the use of at least one selected from the group consisting of spirulina, phycocyanin, and phycocyanobilin for the production of a composition (which may be a food or beverage composition, for example, a health food or beverage) for preventing or improving the symptoms of age-related hearing loss in healthy individuals. Furthermore, this disclosure can provide the use of a composition containing at least one selected from the group consisting of spirulina, phycocyanin, and phycocyanobilin for the production of a composition (which may be a food or beverage composition, for example, a health food or beverage) for preventing or improving the symptoms of age-related hearing loss in healthy individuals.

[0037] In this embodiment, age-related hearing loss includes, for example, hearing loss in the frequency range of 4 kHz or higher, hearing loss in the frequency range of 6 kHz or higher, hearing loss in the frequency range of 8 kHz or higher, hearing loss in the frequency range of 12 kHz or higher, hearing loss in the frequency range of 14 kHz or higher, hearing loss in the frequency range of 16 kHz or higher, hearing loss in the frequency range of 20 kHz or higher, hearing loss in the frequency range of 24 kHz or higher, hearing loss in the frequency range of 28 kHz or higher, hearing loss in the frequency range of 32 kHz or higher, etc. These include hearing loss in the frequency range of 36 kHz or below, 34 kHz or below, 32 kHz or below, 28 kHz or below, 24 kHz or below, 20 kHz or below, 18 kHz or below, 16 kHz or below, 12 kHz or below, and 8 kHz or below. A non-contradictory combination of these is also acceptable. For example, hearing loss can occur in the following frequency ranges: 4kHz to 8kHz, 6kHz to 12kHz, 8kHz to 16kHz, 12kHz to 20kHz, 14kHz to 18kHz, 16kHz to 24kHz, 20kHz to 28kHz, 24kHz to 32kHz, 28kHz to 34kHz, and 32kHz to 36kHz. Furthermore, hearing loss can occur in the 8kHz to 32kHz range, the 16kHz to 32kHz range, and the 12kHz to 36kHz range.

[0038] Furthermore, age-related hearing loss in this embodiment is defined using the age of, for example, an aging-accelerated model mouse (e.g., SAMP8 aging-accelerated model mouse), and includes age-related hearing loss in mice aged 16 weeks or older, age-related hearing loss in mice aged 20 weeks or older, age-related hearing loss in mice aged 24 weeks or older, age-related hearing loss in mice aged 28 weeks or older, age-related hearing loss in mice aged 32 weeks or older, and age-related hearing loss in mice aged 36 weeks or older. Examples include age-related hearing loss in subjects of a certain age or older, while other examples include age-related hearing loss in subjects up to death, age-related hearing loss in subjects under the age equivalent to 40 weeks of age in mice, age-related hearing loss in subjects under the age equivalent to 36 weeks of age in mice, age-related hearing loss in subjects under the age equivalent to 32 weeks of age in mice, age-related hearing loss in subjects under the age equivalent to 28 weeks of age in mice, age-related hearing loss in subjects under the age equivalent to 24 weeks of age in mice, and age-related hearing loss in subjects under the age equivalent to 20 weeks of age in mice. Any non-contradictory combination of these is also acceptable. For example, using the age of aging-accelerated model mice (e.g., SAMP8 aging-accelerated model mice), examples include age-related hearing loss in subjects corresponding to 16 weeks of age to 20 weeks of age in mice, age-related hearing loss in subjects corresponding to 20 weeks of age to 24 weeks of age in mice, age-related hearing loss in subjects corresponding to 24 weeks of age to 28 weeks of age in mice, age-related hearing loss in subjects corresponding to 28 weeks of age to 32 weeks of age in mice, age-related hearing loss in subjects corresponding to 32 weeks of age to 36 weeks of age in mice, age-related hearing loss in subjects corresponding to 36 weeks of age to 40 weeks of age in mice, and age-related hearing loss in subjects corresponding to 36 weeks of age to death in mice. Also, age-related hearing loss in subjects corresponding to 24 weeks of age to 36 weeks of age in mice can be mentioned.

[0039] The start date for the ingestion of the composition of this embodiment by the subject is not particularly limited as long as the subject subsequently exhibits an effect of preventing or improving age-related hearing loss, but it is before the time when such effect is exhibited by the ingestion. Furthermore, ingestion may continue even after the effect begins to be exhibited. Examples of the start date for the ingestion of the composition of this embodiment by the subject include, for example, using the age of an aging-accelerated model mouse (e.g., SAMP8 aging-accelerated model mouse), ages corresponding to 12 weeks of age, 16 weeks of age, 20 weeks of age, 24 weeks of age, 28 weeks of age, 32 weeks of age, 36 weeks of age, etc.

[0040] The end of the period at which the composition of this embodiment is ingested by the subject is not particularly limited, but for example, using the age of an aging-accelerated model mouse (e.g., SAMP8 aging-accelerated model mouse, etc.), examples include the age at death, an age equivalent to 40 weeks of age in a mouse, an age equivalent to 36 weeks of age in a mouse, an age equivalent to 32 weeks of age in a mouse, an age equivalent to 28 weeks of age in a mouse, an age equivalent to 24 weeks of age in a mouse, an age equivalent to 20 weeks of age in a mouse, etc. Furthermore, examples include when the subject no longer desires the effect of preventing or improving age-related hearing loss after ingestion, or when ingestion becomes detrimental to the subject.

[0041] The timing at which the composition of this embodiment is ingested by the subject may be a non-contradictory combination of these timings. For example, using the age of an aging-accelerated model mouse (e.g., SAMP8 aging-accelerated model mouse), examples include ages equivalent to 12 weeks of age in a mouse to 20 weeks of age in a mouse, ages equivalent to 16 weeks of age in a mouse to 24 weeks of age in a mouse, ages equivalent to 20 weeks of age in a mouse to 28 weeks of age in a mouse, ages equivalent to 24 weeks of age in a mouse to 32 weeks of age in a mouse, ages equivalent to 28 weeks of age in a mouse to 36 weeks of age in a mouse, ages equivalent to 32 weeks of age in a mouse to 40 weeks of age in a mouse, ages equivalent to 36 weeks of age in a mouse to death, etc. Also, ages equivalent to 12 weeks of age in a mouse and above may be included. Also, ages equivalent to 12 weeks of age in a mouse to death may be included.

[0042] Furthermore, age-related hearing loss in this embodiment includes, for example, age-related hearing loss in mice aged 36 weeks or older, age-related hearing loss in mice aged 38 weeks or older, age-related hearing loss in mice aged 42 weeks or older, age-related hearing loss in mice aged 46 weeks or older, age-related hearing loss in mice aged 48 weeks or older, age-related hearing loss in mice aged 50 weeks or older, age-related hearing loss in mice aged 52 weeks or older, and so on. Examples include age-related hearing loss in subjects before death, age-related hearing loss in subjects under the age equivalent to 58 weeks of age in mice, age-related hearing loss in subjects under the age equivalent to 56 weeks of age in mice, age-related hearing loss in subjects under the age equivalent to 52 weeks of age in mice, age-related hearing loss in subjects under the age equivalent to 50 weeks of age in mice, age-related hearing loss in subjects under the age equivalent to 48 weeks of age in mice, age-related hearing loss in subjects under the age equivalent to 46 weeks of age in mice, age-related hearing loss in subjects under the age equivalent to 42 weeks of age in mice, and age-related hearing loss in subjects under the age equivalent to 38 weeks of age in mice. Any non-contradictory combination of these may also be acceptable.For example, using the age of C57BL / 6J mice, for example, age-related hearing loss in mice from 36 weeks of age to 38 weeks of age, age-related hearing loss in mice from 38 weeks of age to 42 weeks of age, age-related hearing loss in mice from 42 weeks of age to 46 weeks of age, age-related hearing loss in mice from 46 weeks of age to 50 weeks of age, and age-related hearing loss in mice from 48 weeks of age to 52 weeks of age Age-related hearing loss in mice of an age equivalent to or younger than a certain age; age-related hearing loss in mice of an age equivalent to 38 weeks of age or younger than a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age; age-related hearing loss in mice of an equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain age equivalent to a certain

[0043] The start date for the ingestion of the composition of this embodiment by the subject is not particularly limited as long as the subject subsequently exhibits an effect of preventing or improving age-related hearing loss, but it is before the time when such effect is exhibited by the ingestion. Furthermore, ingestion may continue even after the effect begins to be exhibited. Examples of the start date for the ingestion of the composition of this embodiment by the subject include, using the age of C57BL / 6J mice, ages corresponding to 30 weeks of age, 36 weeks of age, 38 weeks of age, 42 weeks of age, 46 weeks of age, 48 weeks of age, 50 weeks of age, 52 weeks of age, etc.

[0044] The end time when the composition of this aspect is ingested by the subject is not particularly limited. For example, using the age of C57BL / 6J mice, for example, at the time of death, the age corresponding to 58 weeks old in mice, the age corresponding to 56 weeks old in mice, the age corresponding to 52 weeks old in mice, the age corresponding to 50 weeks old in mice, the age corresponding to 48 weeks old in mice, the age corresponding to 46 weeks old in mice, the age corresponding to 42 weeks old in mice, the age corresponding to 38 weeks old in mice, etc. can be mentioned. Also, cases where the effect of preventing or improving presbycusis is no longer desired in the ingested subject, or cases where ingestion becomes disadvantageous to the subject, etc. can be mentioned.

[0045] The time when the composition of this aspect is ingested by the subject may be any non - conflicting combination. For example, using the age of C57BL / 6J mice, for example, the age corresponding to 30 weeks old in mice to the age corresponding to 38 weeks old in mice, the age corresponding to 36 weeks old in mice to the age corresponding to 42 weeks old in mice, the age corresponding to 38 weeks old in mice to the age corresponding to 46 weeks old in mice, the age corresponding to 42 weeks old in mice to the age corresponding to 50 weeks old in mice, the age corresponding to 46 weeks old in mice to the age corresponding to 52 weeks old in mice, the age corresponding to 48 weeks old in mice to the age corresponding to 52 weeks old in mice, the age corresponding to 38 weeks old in mice to the age corresponding to 48 weeks old in mice, the age corresponding to 50 weeks old in mice to the age corresponding to 56 weeks old in mice, the age corresponding to 50 weeks old in mice to the age corresponding to 58 weeks old in mice, the age corresponding to 52 weeks old in mice to the time of death, etc. can be mentioned. Also, the age after the age corresponding to 30 weeks old in mice can be mentioned. Also, the age corresponding to 30 weeks old in mice to the time of death can be mentioned.

[0046] The age equivalent to 30 weeks of age in the C57BL / 6J mouse varies depending on the subject, but can be converted for each subject according to the standard method. For example, if the subject is human, you can refer to, for example, the literature "Life Sciences 242 (2020) 117242" (the same applies below), and it is 31.4 years. The age equivalent to 36 weeks of age in the C57BL / 6J mouse varies depending on the subject, but can be converted for each subject according to the standard method. For example, if the subject is human, it is 34.8 years. The age equivalent to 38 weeks of age in the C57BL / 6J mouse varies depending on the subject, but can be converted for each subject according to the standard method. For example, if the subject is human, it is 36.0 years. The age equivalent to 42 weeks of age in the C57BL / 6J mouse varies depending on the subject, but can be converted for each subject according to the standard method. For example, if the subject is human, it is 38.3 years. The age equivalent to 46 weeks of age in the C57BL / 6J mouse varies depending on the subject, but can be converted for each subject according to the standard method. For example, if the subject is human, it is 40.6 years. The age equivalent to 48 weeks of age in the C57BL / 6J mouse varies depending on the subject, but can be converted for each subject according to the standard method. For example, if the subject is human, it is 41.7 years. The age equivalent to 50 weeks of age in the C57BL / 6J mouse varies depending on the subject, but can be converted for each subject according to the standard method. For example, if the subject is human, it is 42.8 years. The age equivalent to 52 weeks of age in the C57BL / 6J mouse varies depending on the subject, but can be converted for each subject according to the standard method. For example, if the subject is human, it is 44.0 years. The age equivalent to 56 weeks of age in the C57BL / 6J mouse varies depending on the subject, but can be converted for each subject according to the standard method. For example, if the subject is human, it is 46.3 years. The age equivalent to 58 weeks in the aforementioned C57BL / 6J mouse varies depending on the subject, but it can be converted for each subject according to the standard method. For example, if the subject is human, it is 47.4 years old.

[0047] The content of the active ingredient in the composition of this aspect is appropriately set according to the aspect of the composition. In terms of dry mass conversion, in total, for example, it is 10% by mass or more, 20% by mass or more, 50% by mass or more, etc. On the other hand, for example, it is 100% by mass or less, 99% by mass or less, 80% by mass or less, etc. Combinations that are not contradictory may also be used. For example, it is 10% by mass to 100% by mass, 20% by mass to 99% by mass, 50% by mass to 80% by mass, etc.

[0048] The intake amount (effective amount) of the composition of this aspect is appropriately set according to the form, usage, target, age, gender, and other conditions of the composition. However, as long as the effect of preventing or improving presbycusis is exhibited in the subject who has ingested it, there is no particular limitation. In terms of dry mass conversion of the active ingredient, in total, per day and per 60 kg of body weight, for example, it is 0.1 mg or more, 1 mg or more, 10 mg or more, etc. On the other hand, for example, it is 50 g or less, 10 g or less, 5 g or less, etc. Combinations that are not contradictory may also be used. For example, it is 0.1 mg to 50 g, 1 mg to 10 g, 10 mg to 5 g, etc.

[0049] The composition of this aspect can be ingested once a day or divided into multiple times. Also, it may be ingested once every few days or weeks, but it is preferably ingested daily.

[0050] The composition of this aspect can be ingested orally. Also, it can be ingested nasally. Also, it can be ingested through gastrostomy or enterostomy.

[0051] The composition of this embodiment can be used, for example, as a food and beverage composition, a feed composition, a pharmaceutical composition, etc. For example, it can be provided as "a food and beverage composition for preventing or improving age-related hearing loss, containing at least one selected from the group consisting of spirulina, phycocyanin, and phycocyanobilin as an active ingredient." Hereinafter, this may be referred to as "the food and beverage composition of this embodiment." "The food and beverage composition of this embodiment" includes supplements. It can also be provided as "a feed composition for preventing or improving age-related hearing loss, containing at least one selected from the group consisting of spirulina, phycocyanin, and phycocyanobilin as an active ingredient." Hereinafter, this may be referred to as "the feed composition of this embodiment." It can also be provided as "a pharmaceutical composition for preventing or improving age-related hearing loss, containing at least one selected from the group consisting of spirulina, phycocyanin, and phycocyanobilin as an active ingredient." Hereinafter, this may be referred to as "the pharmaceutical composition of this embodiment."

[0052] When the above-mentioned active ingredient is used as a material for the food and beverage composition of this embodiment, it can be used not only as a general food and beverage composition, but also as a food for specified health uses, nutritional supplement, functional food, food for the sick, food additive, etc. (including beverages). As for the form of the food and beverage composition, for example, after adding an appropriate auxiliary agent, it may be molded into a form suitable for consumption, such as granules, tablets, capsules, paste, etc., using conventional means, and then made into food. Alternatively, it may be used as an additive to various foods, such as processed meat products such as ham and sausage, processed seafood products such as kamaboko and chikuwa, bread, confectionery, butter, powdered milk, and fermented dairy products, or as an additive to beverages such as water, fruit juice, milk, and soft drinks.

[0053] The food and beverage composition of this embodiment can be used for any subject, including healthy and unhealthy individuals. However, if it is a food or beverage with a specific use (especially a health use) or function indicated, it may be used for the non-therapeutic purposes described above.

[0054] The food and beverage composition of this embodiment may mainly consist of water, protein, carbohydrates, lipids, vitamins, minerals, organic acids, organic bases, fruit juice, flavors, etc. Examples of proteins include whole milk powder, skim milk powder, partially skim milk powder, casein, soy protein, chicken egg protein, meat protein, and other animal and plant proteins, their hydrolysates, butter, etc. Examples of carbohydrates include sugars, modified starch (dextrin, as well as soluble starch, British starch, oxidized starch, starch esters, starch ethers, etc.), dietary fiber, etc. Examples of lipids include vegetable oils such as lard, safflower oil, corn oil, rapeseed oil, coconut oil, fractionated oils thereof, hydrogenated oil, and transesterified oil. Examples of vitamins include vitamin A, carotenes, B vitamins, vitamin C, vitamin D, vitamin E, vitamin K, vitamin P, vitamin Q, niacin, nicotinic acid, pantothenic acid, biotin, inositol, choline, and folic acid. Examples of minerals include calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc, selenium, and whey minerals. Examples of organic acids include malic acid, citric acid, lactic acid, and tartaric acid.

[0055] The food and beverage composition of this embodiment can be manufactured according to conventional methods. For example, it can be manufactured by adding the active ingredient to the usual raw materials of a food and beverage composition. Except for the addition of the active ingredient, it can be manufactured in the same manner as a normal food and beverage composition. The amount, method, and timing of the addition of the active ingredient can be selected as appropriate. Furthermore, the food and beverage composition of this embodiment can be sealed in appropriate containers such as bottles, bags, cans, boxes, or packs, as needed.

[0056] The content of the active ingredient in the food and beverage composition of this embodiment is set appropriately depending on the embodiment of the food and beverage composition, but on a dry mass basis, in total amount, it is, for example, 10% by mass or more, 20% by mass or more, 50% by mass or more, etc., on the other hand, it is, for example, 100% by mass or less, 99% by mass or less, 80% by mass or less, etc. A non-contradictory combination of these is also acceptable. For example, 10% by mass to 100% by mass, 20% by mass to 99% by mass, 50% by mass to 80% by mass, etc.

[0057] The intake amount (effective amount) of the food and beverage composition in this embodiment is set appropriately depending on the form of the food and beverage composition, method of use, target, target age, sex, and other conditions, but is not particularly limited as long as it exhibits an effect of preventing or improving age-related hearing loss in the target who ingests it. The total amount per day and per 60 kg body weight, calculated on a dry mass basis of the active ingredient, is, for example, 0.1 mg or more, 1 mg or more, 10 mg or more, etc., while on the other hand, it is, for example, 50 g or less, 10 g or less, 5 g or less, etc. Non-contradictory combinations of these are also acceptable. For example, 0.1 mg to 50 g, 1 mg to 10 g, 10 mg to 5 g, etc.

[0058] The food and beverage composition of this embodiment can be consumed once or multiple times a day. It may also be consumed once every few days or weeks, but daily consumption is preferable.

[0059] When the target is a mammal other than a human, the active ingredient can be used as a material for the feed composition of this embodiment. In this case, the feed ingredients and the active ingredient may be appropriately blended according to the breeding environment, such as the type of mammal, developmental stage, and region. Examples of feed ingredients include grains or processed grains (corn, milo, barley, etc.), bran products (wheat bran, rice bran, corn gluten feed, etc.), vegetable oil cakes (soybean oil cake, sesame oil cake, cottonseed oil cake, etc.), animal raw materials (skim milk powder, fish meal, meat and bone meal, etc.), minerals (calcium carbonate, calcium phosphate, sodium chloride, anhydrous silicic acid, etc.), vitamins, amino acids, yeasts such as brewer's yeast, and fine powders of inorganic substances (crystalline cellulose, talc, silica, etc.).

[0060] The feed composition of this embodiment can be used for any subject, including healthy and unhealthy mammals. However, if the feed is labeled with a specific use or function, it may be used for the non-therapeutic purposes described above.

[0061] The feed composition of this embodiment may contain, in addition to the feed ingredients, feed additives such as excipients, bulking agents, binders, thickeners, emulsifiers, colorants, flavorings, food additives, and seasonings commonly used in compound feeds, as well as other components (antibiotics, bactericides, anthelmintics, preservatives, etc.) as desired.

[0062] The form of the feed composition in this embodiment is not particularly limited and may be, for example, powder, granules, paste, pellets, capsules (hard capsules, soft capsules), tablets, etc., and may be used as pet food for companion animals or feed for laboratory animals.

[0063] The content of the active ingredient in the feed composition of this embodiment is set appropriately depending on the form of the feed composition, but on a dry mass basis, in total amount, it may be, for example, 10% by mass or more, 20% by mass or more, 50% by mass or more, on the other hand, it may be, for example, 100% by mass or less, 99% by mass or less, 80% by mass or less, etc. A non-contradictory combination of these may also be used. For example, 10% by mass to 100% by mass, 20% by mass to 99% by mass, 50% by mass to 80% by mass, etc.

[0064] The dosage (effective amount) of the feed composition in this embodiment is set appropriately depending on the form of the feed composition, method of use, target, age, sex of the target, and other conditions, but is not particularly limited as long as it exhibits an effect of preventing or improving age-related hearing loss in the target to which it is administered. The total amount per day and per 60 kg of body weight, calculated on a dry mass basis of the active ingredient, is, for example, 0.1 mg or more, 1 mg or more, 10 mg or more, etc., while on the other hand, it is, for example, 50 g or less, 10 g or less, 5 g or less, etc. Non-contradictory combinations of these are also acceptable. For example, 0.1 mg to 50 g, 1 mg to 10 g, 10 mg to 5 g, etc.

[0065] The feed composition of this embodiment can be administered once a day or in divided doses. It may also be administered once every few days or weeks, but daily administration is preferred.

[0066] When the above-mentioned active ingredient is used as a material for the pharmaceutical composition of this embodiment, the pharmaceutical composition can be administered either orally or parenterally. For administration, the active ingredient can be mixed with a solid or liquid non-toxic pharmaceutical carrier suitable for administration methods such as oral administration, rectal administration, or injection, and administered in the form of a conventional pharmaceutical preparation. Examples of such preparations include solid preparations such as tablets, granules, powders, and capsules, liquid preparations such as solutions, suspensions, and emulsions, and lyophilized preparations, and these preparations can be prepared by conventional pharmaceutical methods. Examples of the above-mentioned non-toxic pharmaceutical carriers include glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glycerides, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid esters, amino acids, gelatin, albumin, water, and physiological saline. In addition, conventional additives such as stabilizers, wetting agents, emulsifiers, binders, and isotonic agents can be added as needed.

[0067] The pharmaceutical composition of this embodiment may be administered to non-healthy individuals for the therapeutic purpose of improving (treating) age-related hearing loss. Furthermore, the pharmaceutical composition of this embodiment may be administered to healthy individuals for the non-therapeutic purpose of preventing age-related hearing loss.

[0068] The content of the active ingredient in the pharmaceutical composition of this embodiment is set appropriately depending on the embodiment of the pharmaceutical composition, but on a dry mass basis, in total amount, it may be, for example, 10% by mass or more, 20% by mass or more, 50% by mass or more, on the other hand, it may be, for example, 100% by mass or less, 99% by mass or less, 80% by mass or less, etc. A non-contradictory combination of these may also be used. For example, 10% by mass to 100% by mass, 20% by mass to 99% by mass, 50% by mass to 80% by mass, etc.

[0069] The dosage (effective dose) of the pharmaceutical composition in this embodiment is set appropriately depending on the form of the pharmaceutical composition, method of use, target, age, sex, and other conditions of the target, but is not particularly limited as long as it exhibits an effect of preventing or improving age-related hearing loss in the target to whom it is administered. The total amount per day and per 60 kg body weight, calculated on a dry weight basis of the active ingredient, is, for example, 0.1 mg or more, 1 mg or more, 10 mg or more, etc., while on the other hand, it is, for example, 50 g or less, 10 g or less, 5 g or less, etc. Non-contradictory combinations of these are also acceptable. For example, 0.1 mg to 50 g, 1 mg to 10 g, 10 mg to 5 g, etc.

[0070] The pharmaceutical composition of this embodiment can be administered once a day or in divided doses. It may also be administered once every few days or weeks, but daily administration is preferred.

[0071] In addition to the embodiments described herein, this disclosure may also provide, for example, the following embodiments: Use of the active ingredient for manufacturing a composition for preventing or improving age-related hearing loss. Use of the active ingredient for preventing or improving age-related hearing loss. Use of a composition containing the active ingredient for preventing or improving age-related hearing loss. Non-therapeutic use of the active ingredient for preventing or improving age-related hearing loss. Non-therapeutic use of a composition containing the active ingredient for preventing or improving age-related hearing loss. The active ingredient for use in preventing or improving age-related hearing loss. A composition containing the active ingredient for use in preventing or improving age-related hearing loss. A non-therapeutic use of the active ingredient, wherein the active ingredient is used for preventing or improving age-related hearing loss. A non-therapeutic use of a composition containing the active ingredient, wherein the composition is used for preventing or improving age-related hearing loss. A method for preventing or improving age-related hearing loss, comprising administering a prophylactic or ameliorative effective amount of the active ingredient to a subject in need of prevention or improvement. A method for preventing or improving age-related hearing loss, comprising administering a prophylactic or ameliorative effective amount of a composition containing the active ingredient to a subject in need of prevention or improvement.

[0072] In addition to the embodiments described herein, this disclosure may also provide, for example, the following embodiments: <1-1> A composition for preventing or improving age-related hearing loss, comprising spirulina as an active ingredient. <1-2> The composition according to <1-1>, wherein the age-related hearing loss is hearing loss in the frequency range of 4 kHz to 12 kHz. <1-3> The composition according to <1-1> or <1-2>, wherein the age-related hearing loss is hearing loss in the frequency range of 6 kHz to 10 kHz. <1-4> The composition according to any one of <1-1> to <1-3>, wherein the age-related hearing loss is age-related hearing loss in a subject aged 28 weeks or older, equivalent to 28 weeks of age in an aging-accelerated model mouse. <1-5> The composition according to any one of <1-1> to <1-4>, wherein the age-related hearing loss is age-related hearing loss in a subject aged 28 weeks or older, equivalent to 40 weeks of age in an aging-accelerated model mouse. <1-6> The composition according to any one of <1-1> to <1-5>, wherein the age-related hearing loss is age-related hearing loss in a mouse model that is between 32 weeks of age and 40 weeks of age.

[0073] <1-7> The composition according to <1-1>, wherein the age-related hearing loss is hearing loss in the frequency range of 12 kHz to 36 kHz. <1-8> The composition according to <1-7>, wherein the age-related hearing loss is hearing loss in the frequency range of 16 kHz to 32 kHz. <1-9> The composition according to <1-7> or <1-8>, wherein the age-related hearing loss is hearing loss in the frequency range of 16 kHz to 24 kHz. <1-10> The composition according to <1-7> or <1-8>, wherein the age-related hearing loss is hearing loss in the frequency range of 24 kHz to 32 kHz. <1-11> The composition according to <1-7>, wherein the age-related hearing loss is hearing loss in the frequency range of 12 kHz to 20 kHz. <1-12> The composition according to <1-7>, wherein the age-related hearing loss is hearing loss in the frequency range of 20 kHz to 28 kHz. <1-13> The composition according to <1-7>, wherein the age-related hearing loss is hearing loss in the frequency range of 28 kHz to 36 kHz. <1-14> The composition according to any one of <1-7> to <1-13>, wherein the age-related hearing loss is age-related hearing loss in an animal of an age equivalent to 20 weeks of age or older in an aging-accelerated model mouse. <1-15> The composition according to any one of <1-7> to <1-14>, wherein the age-related hearing loss is age-related hearing loss in an animal of an age equivalent to 20 weeks of age or older in an aging-accelerated model mouse, up to 40 weeks of age. <1-16> The composition according to any one of <1-7> to <1-15>, wherein the age-related hearing loss is age-related hearing loss in mice aged between 24 weeks and 36 weeks in age-accelerated model mice. <1-17> The composition according to any one of <1-7> to <1-15>, wherein the age-related hearing loss is age-related hearing loss in mice aged between 20 weeks and 28 weeks in age-accelerated model mice. <1-18> The composition according to any one of <1-7> to <1-15>, wherein the age-related hearing loss is age-related hearing loss in mice aged between 32 weeks and 40 weeks in age-accelerated model mice.

[0074] <1-19> The composition according to any one of <1-1> to <1-18>, wherein the period of ingestion by the subject is at or above the age equivalent to 12 weeks of age in an aging-accelerated model mouse. <1-20> The composition according to any one of <1-1> to <1-19>, wherein the period of ingestion by the subject is at or above the age equivalent to 12 weeks of age in an aging-accelerated model mouse until death. <1-21> The composition according to any one of <1-1> to <1-20>, wherein the period of ingestion by the subject is at or above the age equivalent to 12 weeks of age in an aging-accelerated model mouse until 36 weeks of age. <1-22> The composition according to any one of <1-1> to <1-21>, wherein the period of ingestion by the subject is at or above the age equivalent to 12 weeks of age in an aging-accelerated model mouse until 24 weeks of age.

[0075] <2-1> A composition for preventing or improving age-related hearing loss, comprising phycocyanin as an active ingredient. <2-2> The composition according to <2-1>, wherein the age-related hearing loss is hearing loss in the frequency range of 12 kHz to 36 kHz. <2-3> The composition according to <2-1> or <2-2>, wherein the age-related hearing loss is hearing loss in the frequency range of 16 kHz to 32 kHz. <2-4> The composition according to any one of <2-1> to <2-3>, wherein the age-related hearing loss is hearing loss in the frequency range of 16 kHz to 24 kHz. <2-5> The composition according to any one of <2-1> to <2-3>, wherein the age-related hearing loss is hearing loss in the frequency range of 24 kHz to 32 kHz. <2-6> The composition according to <2-1> or <2-2>, wherein the age-related hearing loss is hearing loss in the frequency range of 12 kHz to 20 kHz. <2-7> The composition according to <2-1> or <2-2>, wherein the age-related hearing loss is hearing loss in the frequency range of 20 kHz to 28 kHz. <2-8> The composition according to <2-1> or <2-2>, wherein the age-related hearing loss is hearing loss in the frequency range of 28 kHz to 36 kHz. <2-9> The composition according to any one of <2-1> to <2-8>, wherein the age-related hearing loss is age-related hearing loss in a subject aged 20 weeks or older, equivalent to 20 weeks of age in an aging-accelerated model mouse. <2-10> The composition according to any one of <2-1> to <2-9>, wherein the age-related hearing loss is age-related hearing loss in a subject aged 20 weeks or older, equivalent to 40 weeks of age in an aging-accelerated model mouse. <2-11> The composition according to any one of <2-1> to <2-10>, wherein the age-related hearing loss is age-related hearing loss in mice aged between 24 weeks and 36 weeks in age-accelerated model mice. <2-12> The composition according to any one of <2-1> to <2-10>, wherein the age-related hearing loss is age-related hearing loss in mice aged between 20 weeks and 28 weeks in age-accelerated model mice. <2-13> The composition according to any one of <2-1> to <2-10>, wherein the age-related hearing loss is age-related hearing loss in mice aged between 32 weeks and 40 weeks in age-accelerated model mice.<2-14> The composition according to any one of <2-1> to <2-13>, wherein the period of ingestion by the subject is at or above the age equivalent to 12 weeks of age in an aging-accelerated model mouse. <2-15> The composition according to any one of <2-1> to <2-14>, wherein the period of ingestion by the subject is at or above the age equivalent to 12 weeks of age in an aging-accelerated model mouse until death. <2-16> The composition according to any one of <2-1> to <2-15>, wherein the period of ingestion by the subject is at or above the age equivalent to 12 weeks of age in an aging-accelerated model mouse until 36 weeks of age. <2-17> The composition according to any one of <2-1> to <2-16>, wherein the period of ingestion by the subject is at or above the age equivalent to 12 weeks of age in an aging-accelerated model mouse until 24 weeks of age.

[0076] <2-18> The composition according to <2-1>, wherein the subject is male and the age-related hearing loss is hearing loss in the frequency range of 4 kHz to 12 kHz. <2-19> The composition according to <2-18>, wherein the age-related hearing loss is hearing loss in the frequency range of 6 kHz to 10 kHz. <2-20> The composition according to <2-18> or <2-19>, wherein the age-related hearing loss is age-related hearing loss in a subject aged between 36 weeks and 48 weeks of age in C57BL / 6J mice. <2-21> The composition according to any one of <2-18> to <2-20>, wherein the age-related hearing loss is age-related hearing loss in a subject aged between 38 weeks and 46 weeks of age in C57BL / 6J mice.

[0077] <2-22> The composition according to <2-1>, wherein the subject is male and the age-related hearing loss is hearing loss in the frequency range of 12 kHz to 36 kHz. <2-23> The composition according to <2-22>, wherein the age-related hearing loss is hearing loss in the frequency range of 16 kHz to 32 kHz. <2-24> The composition according to <2-22> or <2-23>, wherein the age-related hearing loss is hearing loss in the frequency range of 16 kHz to 24 kHz. <2-25> The composition according to <2-22> or <2-23>, wherein the age-related hearing loss is hearing loss in the frequency range of 24 kHz to 32 kHz. <2-26> The composition according to <2-22>, wherein the age-related hearing loss is hearing loss in the frequency range of 12 kHz to 20 kHz. <2-27> The composition according to <2-22>, wherein the age-related hearing loss is hearing loss in the frequency range of 20 kHz to 28 kHz. <2-28> The composition according to <2-22>, wherein the age-related hearing loss is hearing loss in the frequency range of 28 kHz to 36 kHz. <2-29> The composition according to any one of <2-22> to <2-28>, wherein the age-related hearing loss is age-related hearing loss in an animal aged 38 weeks or older, equivalent to a C57BL / 6J mouse. <2-30> The composition according to any one of <2-22> to <2-29>, wherein the age-related hearing loss is age-related hearing loss in an animal aged 38 weeks or older, equivalent to a C57BL / 6J mouse, or aged 56 weeks or younger. <2-31> The composition according to any one of <2-22> to <2-30>, wherein the age-related hearing loss is age-related hearing loss in a C57BL / 6J mouse aged between 42 weeks of age and 52 weeks of age. <2-32> The composition according to any one of <2-22> to <2-30>, wherein the age-related hearing loss is age-related hearing loss in a C57BL / 6J mouse aged between 38 weeks of age and 46 weeks of age. <2-33> The composition according to any one of <2-22> to <2-30>, wherein the age-related hearing loss is age-related hearing loss in a C57BL / 6J mouse aged between 48 weeks of age and 56 weeks of age.

[0078] <2-34> The composition according to <2-1>, wherein the subject is male and the age-related hearing loss is hearing loss in the frequency range of 12 kHz to 20 kHz. <2-35> The composition according to <2-34>, wherein the age-related hearing loss is hearing loss in the frequency range of 14 kHz to 18 kHz. <2-36> The composition according to <2-34> or <2-35>, wherein the age-related hearing loss is age-related hearing loss in a subject aged between 36 weeks and 48 weeks of age in C57BL / 6J mice. <2-37> The composition according to any one of <2-34> to <2-36>, wherein the age-related hearing loss is age-related hearing loss in a subject aged between 38 weeks and 46 weeks of age in C57BL / 6J mice.

[0079] <2-38> The composition according to any one of <2-1> to <2-37>, wherein the period of ingestion by the subject is at an age equivalent to 30 weeks of age or older in C57BL / 6J mice. <2-39> The composition according to any one of <2-1> to <2-38>, wherein the period of ingestion by the subject is at an age equivalent to 30 weeks of age or older in C57BL / 6J mice until death. <2-40> The composition according to any one of <2-1> to <2-39>, wherein the period of ingestion by the subject is at an age equivalent to 30 weeks of age or older and up to 52 weeks of age in C57BL / 6J mice. <2-41> The composition according to any one of <2-1> to <2-40>, wherein the period of ingestion by the subject is at an age equivalent to 30 weeks of age or older and up to 42 weeks of age in C57BL / 6J mice.

[0080] <3-1> A composition for preventing or improving age-related hearing loss, comprising phycocyanobilin as an active ingredient. <3-2> The composition according to <3-1>, wherein the age-related hearing loss is hearing loss in the frequency range of 12 kHz to 36 kHz. <3-3> The composition according to <3-1> or <3-2>, wherein the age-related hearing loss is hearing loss in the frequency range of 16 kHz to 32 kHz. <3-4> The composition according to any one of <3-1> to <3-3>, wherein the age-related hearing loss is hearing loss in the frequency range of 16 kHz to 24 kHz. <3-5> The composition according to any one of <3-1> to <3-3>, wherein the age-related hearing loss is hearing loss in the frequency range of 24 kHz to 32 kHz. <3-6> The composition according to <3-1> or <3-2>, wherein the age-related hearing loss is hearing loss in the frequency range of 12 kHz to 20 kHz. <3-7> The composition according to <3-1> or <3-2>, wherein the age-related hearing loss is hearing loss in the frequency range of 20 kHz to 28 kHz. <3-8> The composition according to <3-1> or <3-2>, wherein the age-related hearing loss is hearing loss in the frequency range of 28 kHz to 36 kHz. <3-9> The composition according to any one of <3-1> to <3-8>, wherein the age-related hearing loss is age-related hearing loss in a subject aged 20 weeks or older, equivalent to 20 weeks of age in an aging-accelerated model mouse. <3-10> The composition according to any one of <3-1> to <3-9>, wherein the age-related hearing loss is age-related hearing loss in a subject aged 20 weeks or older, equivalent to 40 weeks of age in an aging-accelerated model mouse. <3-11> The composition according to any one of <3-1> to <3-10>, wherein the age-related hearing loss is age-related hearing loss in mice aged between 24 weeks and 36 weeks in age-accelerated model mice. <3-12> The composition according to any one of <3-1> to <3-10>, wherein the age-related hearing loss is age-related hearing loss in mice aged between 20 weeks and 28 weeks in age-accelerated model mice. <3-13> The composition according to any one of <3-1> to <3-10>, wherein the age-related hearing loss is age-related hearing loss in mice aged between 32 weeks and 40 weeks in age-accelerated model mice.<3-14> The composition according to any one of <3-1> to <3-13>, wherein the period of ingestion by the subject is at or above the age equivalent to 12 weeks of age in an aging-accelerated model mouse. <3-15> The composition according to any one of <3-1> to <3-14>, wherein the period of ingestion by the subject is at or above the age equivalent to 12 weeks of age in an aging-accelerated model mouse until death. <3-16> The composition according to any one of <3-1> to <3-15>, wherein the period of ingestion by the subject is at or above the age equivalent to 12 weeks of age in an aging-accelerated model mouse until 36 weeks of age. <3-17> The composition according to any one of <3-1> to <3-16>, wherein the period of ingestion by the subject is at or above the age equivalent to 12 weeks of age in an aging-accelerated model mouse until 24 weeks of age.

[0081] The present disclosure will be specifically described below with reference to examples, but the present disclosure is not limited to these examples.

[0082] [Test Example 1] (Test Substance) Spirulina, phycocyanin, or phycocyanobilin were used as the test substance.

[0083] Spirulina was prepared using a conventional method as follows: Spirulina platensis was propagated in an outdoor culture pond under basic conditions (pH 11). Next, the propagated Spirulina platensis was washed with water and spray-dried to obtain an algal powder.

[0084] Phycocyanin was prepared by a conventional method as follows: 65 kg of dried spirulina algae (spray-dried) produced in an outdoor culture tank was added to 1,300 L of a 1% calcium chloride (anhydrous) solution and stirred for 15 minutes to form a homogeneous suspension. The phycocyanin from the dried spirulina algae was then extracted into the solution under static conditions at 20°C for 15 hours to obtain an extract. 32 kg of sodium dihydrogen phosphate was added to this extract and stirred for 0.5 hours. The reaction was then carried out at 20°C for 2.5 hours under static conditions to produce calcium phosphate, and impurities from the phycocyanin were adsorbed onto the calcium phosphate. The extract after this adsorption treatment was led to a centrifuge and centrifuged at a gravitational acceleration of 10,000 G for 15 minutes to remove the residue of dried spirulina algae and adsorbed substances from the extract. The obtained phycocyanin extract was subjected to ultrafiltration using a separation membrane with a molecular weight cutoff of 10,000 to remove low molecular weight components and salts, and then freeze-dried to obtain phycocyanin. The phycocyanin content was approximately 70% by mass (approximately 22% by mass of C-phycocyanin and approximately 19% by mass of allophycocyanin) per 100% by mass of the phycocyanin pigment powder.

[0085] Phycocyanobilin was prepared by a conventional method as follows: The phycocyanin powder prepared by the above method was suspended in a 99.5% by mass ethanol solution 100 times its weight, and thermal extraction was performed at 100°C and 0.13–0.16 MPa for 1 hour. The resulting solution was separated into solid and liquid by suction filtration using filter paper No. 5A to separate the phycocyanin powder residue from the extract. The ethanol was thoroughly distilled using a rotary evaporator, frozen at -45°C, and then dried by freeze-drying to obtain phycocyanobilin powder (containing 29.9% phycocyanobilin by weight).

[0086] (Study) SAMP8 senescence-accelerated model mice (female) were used as test animals. The SAMP8 senescence-accelerated model mice used in this study have been reported to develop age-related hearing loss from 37 days of age (9 weeks of age) (A. Marie et al., “Senescence-accelerated mouse prone 8 (SAMP8) as a model of age-related hearing loss”, Neuroscience Letters 656 (2017) 138-143), and are widely used as an evaluation model for age-related hearing loss. The mice were divided into the following groups. The samples administered to each group were as follows. - Control group (7 mice): Standard purified mouse feed - Test group 1 (7 mice): Standard purified mouse feed supplemented with spirulina (spirulina content in feed: 10% by mass) - Test group 2 (7 mice): Standard purified mouse feed supplemented with phycocyanin (phycocyanin content in feed: 1.3% by mass) - Test group 3 (7 mice): Standard purified mouse feed supplemented with phycocyanobilin (phycocyanobilin content in feed: 0.15% by mass)

[0087] The above-mentioned samples were administered to mice at 12 weeks of age. Auditory brainstem response (ABR) tests were performed immediately before administration (11 weeks of age), 12 weeks after administration (24 weeks of age), and 24 weeks after administration (36 weeks of age) to assess the degree of age-related hearing loss. Specifically, needle electrodes were inserted into the skin of various parts of the anesthetized mice (top of the head and cheeks) to measure the auditory brainstem response to auditory stimuli. During the measurements, the mice were placed on a warming mat to maintain their body temperature. Pure tones below 100 dB (8, 16, 24, 32 kHz) were used as auditory stimuli, and thresholds were determined at 5 dB intervals.

[0088] (Results) The results are shown in Tables 1 to 4. The values ​​in the tables are mean ± standard error (n=7), and a lower mean indicates better results. Also, a lower mean compared to the control group indicates that an effect was confirmed. The results in parentheses show the t-test results for the control group. Note that for the 11-week-old results, the mice were randomly divided into groups, so although there are differences in values ​​between groups, there is no statistically significant difference.

[0089]

[0090]

[0091]

[0092]

[0093] [Test Example 2] (Test Substance) Phycocyanin was used as the test substance. The phycocyanin used was prepared in the same manner as in Test Example 1.

[0094] (Experiment) C57BL / 6J mice (29 weeks old, 18 males) were prepared as test animals. Each cage was filled with sawdust bedding and a paper dome. Body weight, food intake, and water intake were measured weekly. After one week of acclimatization, hearing was measured using the Auditory Brainstem Response (ABR) test and a grip strength test (described below) was performed. The mice were divided into the following groups to avoid differences in hearing. The samples administered to each group were as follows: ・Control group (9 males): Standard purified mouse feed (AIN93M standard purified; Oriental Yeast Co., Ltd.) ・Test group 4 (9 males): Standard purified mouse feed (AIN93M standard purified; Oriental Yeast Co., Ltd.) supplemented with phycocyanin (phycocyanin content in the feed was 1.3% by mass)

[0095] The above samples were administered to mice at 30 weeks of age. Auditory brainstem response (ABR) tests were performed before administration of the above samples (30 weeks of age), 12 weeks after administration (42 weeks of age), and 22 weeks after administration (52 weeks of age) to assess the degree of age-related hearing loss. Specifically, a triple anesthetic mixture (medetomidine hydrochloride, midazolam, and butorphanol tartrate) was administered intraperitoneally, and needle electrodes were inserted into the skin of the crown, cheek, and back to measure the auditory brainstem response (evoked electroencephalogram) to auditory stimuli. During anesthesia and while awake, the mice were placed on a warming mat to maintain their body temperature. Pure tones below 100 dB (8, 16, 24, 32 kHz) were used as auditory stimuli, and thresholds were determined at 5 dB intervals.

[0096] (Results) The results are shown in Tables 5 to 8. The values ​​in the tables are mean ± standard error (male n=9), and a lower mean indicates better results. Also, a lower mean compared to the control group indicates that the effect was confirmed. The t-test results are for the control group. Note that for the 30-week-old results, the mice were randomly divided into groups, so although there are differences in values ​​between groups, there is no statistically significant difference.

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Claims

1. A composition for preventing or improving age-related hearing loss, comprising at least one selected from the group consisting of spirulina, phycocyanin, and phycocyanobilin as an active ingredient.

2. The composition according to claim 1, wherein the age-related hearing loss is a decrease in hearing in the frequency range of 12 kHz to 36 kHz.

3. The composition according to claim 2, wherein the age-related hearing loss is age-related hearing loss in a subject that is 20 weeks old or older, corresponding to an age-accelerated model mouse.

4. The composition according to claim 1, comprising spirulina as an active ingredient, wherein the age-related hearing loss is a decrease in hearing in the frequency range of 4 kHz to 12 kHz.

5. The composition according to claim 4, wherein the age-related hearing loss is age-related hearing loss in subjects of an age equivalent to 28 weeks or older in an aging-accelerated model mouse.

6. The composition according to claim 1, comprising phycocyanin as an active ingredient, wherein the target is male, and the age-related hearing loss is a hearing loss in the frequency range of 4 kHz to 12 kHz.

7. The composition according to claim 6, wherein the age-related hearing loss is age-related hearing loss in C57BL / 6J mice aged between 36 weeks of age and 48 weeks of age.

8. The composition according to claim 1, comprising phycocyanin as an active ingredient, wherein the target is male, and the age-related hearing loss is a hearing loss in the frequency range of 12 kHz to 36 kHz.

9. The composition according to claim 8, wherein the age-related hearing loss is age-related hearing loss in a subject that is 38 weeks old or older, corresponding to the age of a C57BL / 6J mouse.

10. A food or beverage composition according to any one of claims 1 to 9.

11. A pharmaceutical composition, as described in any one of claims 1 to 9.

12. A feed composition according to any one of claims 1 to 9.

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