Composition for treatment and / or prevention of hearing disorders

Abstract

The present invention provides a composition for the treatment and / or prevention of hearing disorders comprising an asparagus extract, or a composition for the maintenance and / or improvement of hearing function comprising an asparagus extract.

Description

TECHNICAL FIELD

[0001] This patent application is a patent application claiming priority from Japanese Patent Application No. 2023-104149, which is hereby incorporated by reference in its entirety into the present specification.

[0002] The present application relates to a composition for treating and / or preventing a hearing disorder, or a composition for maintaining and / or improving a hearing function. BACKGROUND

[0003] The World Health Organization (WHO) has reported that more than 1 billion young people are at risk of noise-induced hearing loss due to exposure to environments with very large volumes for the purpose of music appreciation and the like. Presbycusis is considered a major risk factor for dementia, and countermeasures against hearing loss are also important as countermeasures against dementia. Presbycusis and noise-induced hearing loss are considered to occur due to the gradual suppression of auditory hair cells in the inner ear due to noise and aging. Since auditory hair cells are difficult to regenerate, treatment of hearing loss is difficult, and prevention in daily life is required. Tinnitus is a sensory abnormality in which sound is perceived despite the absence of sound stimuli, and tinnitus and its associated symptoms cause a large psychological burden. Hearing loss is considered to be one of the causes of tinnitus.

[0004] Asparagus officinalis is a vegetable that is produced and consumed in many countries, and has been found to have various physiological activities. For example, it is known that Asparagus officinalis stem extract has a preventive and restorative effect on various fatigue (physical fatigue, fatigue due to mental stress, etc.), a brain function improving effect, and Asparagus Cladophylls extract has an autonomic nerve regulation effect. Patent Literature 1 describes that a hydroxymethylfurfural derivative from Asparagus officinalis hot water heating treatment product has excellent HSP inducing activity, stress resistance effect, and autonomic nerve regulation effect. However, the effect of Asparagus officinalis extract on hearing disorders or hearing function is unknown.

[0005] PRIOR ART DOCUMENT

[0006] PATENT LITERATURE

[0007] Patent Literature 1: International Publication No. 2013 / 094676 pamphlet SUMMARY

[0008] PROBLEMS TO BE SOLVED BY THE INVENTION

[0009] An object of the present disclosure is to provide a method for treating and / or preventing a hearing disorder, or a method for maintaining and / or improving a hearing function.

[0010] SOLUTION TO PROBLEM

[0011] The present inventors have found that asparagus officinalis extract is effective for improving hearing loss and tinnitus.

[0012] Therefore, in one aspect, the present disclosure provides a composition for treating and / or preventing a hearing disorder, comprising asparagus officinalis extract.

[0013] In another aspect, the present disclosure provides a composition for maintaining and / or improving hearing function, comprising asparagus officinalis extract.

[0014] Effects of the Invention

[0015] According to the present disclosure, a new means for treating and / or preventing a hearing disorder, or for maintaining and / or improving hearing function is provided. BRIEF DESCRIPTION OF DRAWINGS

[0016] FIG. 1 Results of administering a 32 kHz sound stimulus and performing ABR examination on an aged hearing loss mouse model administered with a control feed or a test feed containing asparagus officinalis extract are shown.

[0017] FIG. 2 THI total scores of the asparagus officinalis extract group and the placebo group in a clinical trial investigating the effects of intake of asparagus officinalis extract on tinnitus in healthy persons are shown. DETAILED DESCRIPTION

[0018] Unless otherwise indicated, the terms used in this specification have the meanings commonly understood by those of ordinary skill in the art in the fields of organic chemistry, medicine, pharmacology, molecular biology, microbiology, and the like. The following definitions are intended to apply uniformly throughout the specification and claims unless otherwise indicated.

[0019] In this specification, where a term is followed by “about,” the term is intended to include the range of values ±10% of the value. For example, “about 20” includes “18-22”. Numerical ranges include all values from and including the lower and the upper values, in increments of one unit. In the range “about x to y,” “about” is used before x and y to indicate that x and y are also about the actual values. Thus, for example, “about 20 to 30” includes “about 20 to about 30” and includes the end points, 20 and 30.

[0020] The asparagus extract of the present disclosure is a mixture of components from asparagus contained in a liquid obtained by subjecting asparagus to hot water extraction treatment and removing the residue. The raw material of the asparagus extract is preferably the stem portion (asparagus stem) of asparagus (Asparagus officinalis), including the tender stem and the leaf. The asparagus stem can also use a cut-off portion that is discarded for the efficiency of harvesting, transportation, or sale of asparagus for consumption, and the like. In addition, the raw material of the asparagus extract can be, for example, raw asparagus, a raw material obtained by drying asparagus, or a raw material obtained by powdering dried asparagus. Examples of asparagus include green asparagus, white asparagus, and purple asparagus, and green asparagus is preferred. The origin of the asparagus is not particularly limited.

[0021] The production method of the asparagus extract of the present disclosure includes a step of subjecting asparagus to hot water extraction treatment. "Subjecting to hot water extraction treatment" means extracting components contained in the raw material into water by heating the raw material in hot water. The step of subjecting asparagus to hot water extraction treatment is performed, for example, by adding 1 to 50 times the amount of water to asparagus and heating in hot water for 20 to 180 minutes. The temperature at this time is preferably, for example, 50 to 300°C. In the case of performing hot water extraction treatment under atmospheric pressure, a temperature of 90°C or higher is preferred. Note that hot water extraction treatment can also be performed under pressure, and a pressure of 0.1 to 0.2 MPa (0.12 MPa, for example, in the case of using an autoclave) is preferred.

[0022] In order to improve the efficiency of the hot water extraction treatment step, the production method of the asparagus extract of the present disclosure can further include the following exemplary additional steps.

[0023] As an additional step, for example, a step of chopping asparagus before hot water extraction treatment can be cited. Asparagus can be chopped to a size of, for example, about 0.1 to 10 cm. In the chopping, manual work can be performed using a knife, a cutter, or the like, or a machine such as a chopper or a mill can be used.

[0024] As an additional step, for example, a step of pressing asparagus before hot water extraction treatment can be cited. Asparagus can be pressed, for example, using a press.

[0025] As an additional process, for example, a process of performing enzyme treatment before or after the process of hot water extraction treatment for the purpose of disintegrating the plant tissue or the like can be mentioned. By performing enzyme treatment, the efficiency of the process of hot water extraction treatment can be further improved. For example, in order to effectively decompose fibers, pectin or the like in asparagus, it is appropriate to use enzymes such as cellulase, hemicellulase, pectinase, amylase, pullulanase or the like, or a combination of two or more kinds of these enzymes. In the process of enzyme treatment, the most appropriate amount of addition, temperature and reaction time with respect to the used enzyme can be selected. In the case of using cellulase, for example, enzyme treatment can be performed at a cellulase addition amount of 0.1 to 5% (w / w) at a temperature of 30 to 60°C for 1 to 72 hours. In the case of using pectinase, for example, enzyme treatment can be performed at a pectinase addition amount of 0.1 to 10% (w / w) at a temperature of 30 to 60°C for 1 to 72 hours. The process of enzyme treatment can be performed before the process of hot water extraction treatment, or can be performed after the process of hot water extraction treatment. It is preferable to perform enzyme treatment using cellulase and / or pectinase after the process of hot water extraction treatment.

[0026] As an additional process, for example, a process of mechanically pulverizing the residue after the hot water extraction treatment can be mentioned. In the pulverization, for example, a mill, a mixer or the like can be used.

[0027] As an additional process, for example, a process of centrifugal separation or filtration after the hot water extraction treatment can be mentioned. By further including these processes, the residue can be effectively removed to obtain a heat-treated liquid. The centrifugal separation can be performed at a rotation speed of 3,000 to 7,000 rpm at 4 to 50°C, for example. In the filtration, for example, a commercially available filter paper, filter cloth or the like can be used.

[0028] As an additional process, for example, a process of concentrating the obtained heat-treated liquid under reduced pressure after the hot water extraction treatment can be mentioned. The concentration can be performed using an evaporator or the like, for example.

[0029] As an additional process, for example, a process of spray drying or freeze drying the heat-treated liquid after the hot water extraction treatment can be mentioned. The spray drying can be performed at an exhaust temperature of 70 to 90°C and a chamber temperature of 80 to 100°C, for example. Before the spray drying or freeze drying, an excipient can be added to the heat-treated liquid. Examples of the excipient include starch, starch decomposed product, dextrin, malt dextrin, malt oligosaccharide, lactose, sorbitol, mannitol, white sugar. After the spray drying or freeze drying, the product can be sieved.

[0030] In one embodiment, the method for producing an asparagus extract includes the following processes.

[0031] (1) a process of performing hot water extraction treatment on asparagus to obtain a hot water extraction treatment product,

[0032] (2) a step of performing enzyme treatment on the hot water extraction-treated product to obtain an enzyme-treated product,

[0033] (3) a step of removing residues from the enzyme-treated product to obtain an enzyme-treated liquid,

[0034] (4) a step of concentrating the enzyme-treated liquid and performing spray drying and / or freeze drying to obtain an asparagus extract.

[0035] In one embodiment, the method for producing an asparagus extract includes the following steps.

[0036] (1) a step of performing enzyme treatment on asparagus to obtain an enzyme-treated product,

[0037] (2) a step of performing hot water extraction treatment on the enzyme-treated product to obtain a hot water extraction-treated product,

[0038] (3) a step of removing residues from the hot water extraction-treated product to obtain a heat-treated liquid,

[0039] (4) a step of concentrating the heat-treated liquid and performing spray drying and / or freeze drying to obtain an asparagus extract.

[0040] The following illustrates a method for producing an asparagus extract.

[0041] Method Example 1: Asparagus stems are cut into pieces of about 0.1 to 10 cm, and 1 to 50 times the amount of water is added. Hot water extraction treatment is performed at 50 to 100°C, or under pressure at 121°C for 20 to 180 minutes. After cooling, 0.1 to 5% (w / w) of cellulase is added, and enzyme treatment is performed at 30 to 60°C for 1 to 72 hours. The residues are mechanically pulverized, and centrifugation is performed at 3,000 to 7,000 rpm and 4 to 50°C, whereby a supernatant is obtained. The supernatant is subjected to spray drying at an exhaust temperature of 70 to 90°C and a chamber temperature of 80 to 100°C.

[0042] Method Example 2: Asparagus stems are cut into pieces of about 0.1 to 10 cm, and 1 to 50 times the amount of water is added. Hot water extraction treatment is performed at 50 to 100°C, or under pressure at 121°C for 20 to 180 minutes. After cooling, 0.1 to 5% (w / w) of cellulase is added, and enzyme treatment is performed at 30 to 60°C for 1 to 72 hours. 0.1 to 10% (w / w) of pectinase is added, and enzyme treatment is performed at 30 to 60°C for 1 to 72 hours. The enzymes are inactivated by heat treatment. Centrifugation is performed at 3,000 to 7,000 rpm and 4 to 50°C, whereby a supernatant is obtained. The supernatant is concentrated, an excipient is added, and sterilization is performed under pressure. Spray drying or freeze drying is performed at an exhaust temperature of 70 to 90°C and a chamber temperature of 80 to 100°C.

[0043] Method Example 3: The dried material of the asparagus stem is powdered, and 1 to 50 times the amount of water is added. Hot water extraction treatment is performed at 50 to 100°C, or under pressure at 121°C for 20 to 180 minutes. After cooling, 0.1 to 5% (w / w) of cellulase and 0.1 to 10% (w / w) of pectinase are added, and enzyme treatment is performed at 30 to 60°C for 1 to 72 hours. The enzyme is inactivated by heat treatment. Centrifugal separation is performed at 3,000 to 7,000 rpm, 4 to 50°C, and thus a supernatant is obtained. The supernatant is concentrated, an excipient is added, and sterilization is performed under pressure. Spray drying or freeze drying is performed at an exhaust temperature of 70 to 90°C, and a chamber temperature of 80 to 100°C.

[0044] Typically, the aspartic acid contained in the asparagus extract is 10% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1% or less, 0.5% or less, 0.3% or less, or 0.25% or less.

[0045] As shown in the examples described later, the composition of the present disclosure is capable of treating and / or preventing a hearing disorder. In the present disclosure, a hearing disorder includes hearing loss and tinnitus. In some embodiments, the hearing disorder is not accompanied by other diseases, such as Meniere's disease.

[0046] Hearing loss is one of the most common sensory organ disorders, and is characterized by a decrease in hearing. Hearing loss includes presbycusis, noise-induced hearing loss, and drug-induced hearing loss, and particularly presbycusis. Examples of noise-induced hearing loss include noise-induced hearing loss and occupational hearing loss. Hearing loss can be diagnosed by a pure-tone audiometry, a speech audiometry, a speech recognition score, a tympanometry, a stapedius reflex, and the like.

[0047] Tinnitus is the perception of sound in the absence of a sound stimulus. Tinnitus can be evaluated, for example, by a Tinnitus Handicap Inventory (THI). The THI questionnaire contains 25 items, and the subject selects an answer from "often" (4 points), "sometimes" (2 points), and "none" (0 points) for each item, and the degree of handicap of tinnitus is determined based on the total score. The original version of the THI is in English, and has been translated into multiple languages including Japanese, and the appropriateness and reliability have been verified. The higher the THI score, the higher the degree of handicap of tinnitus, and the degree of handicap is determined as mild at 18 to 36 points, moderate at 38 to 56 points, and severe at 58 to 100 points. In some embodiments, the tinnitus is tinnitus determined as mild or moderate in the THI.

[0048] As used in the present specification, "treatment" or "treating" means delaying or stopping the progression of a hearing disorder, and / or alleviating, relieving, ameliorating, or eliminating a hearing disorder, in a subject having a hearing disorder.

[0049] In the present disclosure, "prevention" or "preventing" means preventing the occurrence of hearing impairment or reducing the possibility of occurrence of hearing impairment for a subject, particularly a subject who is likely to have hearing impairment but has not yet had it. The subject who is likely to have hearing impairment but has not yet had it includes a subject who has a risk factor for hearing impairment. The risk factor for hearing impairment includes, for example, advanced age (e.g., 50 years of age or older, 55 years of age or older, 60 years of age or older, 65 years of age or older, 70 years of age or older, or 75 years of age or older), exposure to noise or loud sound, change in air pressure, stress, accumulation of earwax, blood flow disorder in the inner ear, viral infection, pharmaceutical agent (antibacterial agent, anticancer agent, salicylate-based agent, etc.), acoustic neuroma, otitis media (chronic otitis media, otitis media with effusion, etc.), head trauma, autoimmune disease, and genetics.

[0050] The subject of treatment and / or prevention of hearing impairment is an animal, typically a mammal, such as a human, a non-human primate (e.g., a monkey, a gibbon, a chimpanzee, an orangutan, or a macaque), a pet (e.g., a dog or a cat), a livestock (e.g., a horse, a cow, a goat, a sheep, or a pig), or a laboratory animal (e.g., a mouse, a rat, a rabbit, or a guinea pig), preferably a human. The age of the human subject is not limited, and can be, for example, middle-aged or older, specifically 50 years of age or older, 55 years of age or older, 60 years of age or older, 65 years of age or older, 70 years of age or older, or 75 years of age or older. In some embodiments, the subject does not have Meniere's disease.

[0051] As shown in the examples described later, the composition of the present application can maintain and / or improve hearing function. In the present disclosure, the maintenance of hearing function includes the maintenance of hearing and the suppression of the decrease in hearing. The improvement of hearing function includes the improvement of hearing, the maintenance of the improved state of hearing, and the suppression of the decrease in hearing from the improved state. Hearing can be measured by pure tone audiometry.

[0052] The subject of maintenance and / or improvement of hearing function is an animal, typically a mammal, such as a human, a non-human primate (e.g., a monkey, a gibbon, a chimpanzee, an orangutan, or a macaque), a pet (e.g., a dog or a cat), a livestock (e.g., a horse, a cow, a goat, a sheep, or a pig), or a laboratory animal (e.g., a mouse, a rat, a rabbit, or a guinea pig), preferably a human. The age of the human subject is not limited, and can be, for example, middle-aged or older, specifically 50 years of age or older, 55 years of age or older, 60 years of age or older, 65 years of age or older, 70 years of age or older, or 75 years of age or older. The subject can or can not have hearing impairment. In some embodiments, the subject does not have Meniere's disease.

[0053] The composition of the present disclosure can be a pharmaceutical composition or a quasi-pharmaceutical composition. The asparagus extract can be prepared into a dosage form such as a tablet, a granule, a powder, a capsule, a syrup, an injection, etc. by a conventional method. In addition, an excipient, a binder, a lubricant, a colorant, a disintegrant, a thickening agent, a preservative, a stabilizer, a pH adjustor, etc. commonly used in pharmaceutical products can be added. The administration method of the pharmaceutical composition or the quasi-pharmaceutical composition is not particularly limited, for example, oral administration, intravenous administration, intraperitoneal administration, intradermal administration, or sublingual administration, and is preferably oral administration.

[0054] In addition, the composition of the present disclosure can be a food composition. The food composition can be in the form of a general processed food, for example, can be a food or beverage in a solid form, a beverage agent, a powdered beverage, a soup, etc. to be consumed in a liquid form. The food composition can be consumed as, for example, a juice, a snack, a jelly, a tablet, a dressing, a seasoning, etc. The food composition can be manufactured by processing the asparagus extract into a form suitable for consumption such as a granular form, a particulate form, a tablet, a capsule, a gel form, a cream form, a paste form, a suspension form, an aqueous solution form, an emulsion form, a powder form, etc. by a conventional method. In addition, an excipient, a binder, a lubricant, a colorant, a disintegrant, a thickening agent, a preservative, a stabilizer, a pH adjustor, etc. commonly used in foods can be added. Further, in order to improve the taste, a saccharide, a sugar alcohol, a salt, an oil, an amino acid, an organic acid, glycerin, etc. can be added. The existing food can be made to contain the asparagus extract, and the base food is not particularly limited.

[0055] In addition, such a food can be provided as a health functional food or a dietary supplement. The health functional food includes, for example, a specific health food, a nutrition functional food, and a functionally labeled food. For the health functional food, a mark for a use such as maintaining and / or improving auditory function, etc. can be marked. The mark can be directly marked on a package, a container, a label, a tag, an accessory, etc. accompanying the product, or can be indirectly marked through an advertising campaign. The dietary supplement includes, for example, a nutrition aid food and a health aid food.

[0056] The amount of administration or ingestion of the composition of the present disclosure is not particularly limited. It can be set in consideration of the subject's sex, age, body weight, general health condition, disease condition, and the like. For example, the amount of administration or ingestion of the composition of the present disclosure can be set to an amount of about 50 mg to 2000 mg, about 50 mg to 1350 mg, about 100 mg to 1000 mg, about 100 mg to 500 mg, about 100 mg to 300 mg, about 100 mg to 200 mg, about 110 to 190 mg, about 120 to 180 mg, about 130 to 170 mg, about 140 to 160 mg, or about 145 to 155 mg, for example, about 150 mg, of asparagus extract per day. The amount of administration or ingestion of asparagus extract per day can be contained in one composition, or can be dispersedly contained in a plurality of compositions administered or ingested per day.

[0057] The composition of the present disclosure can be administered or ingested once or a plurality of times. In the case of administration or ingestion a plurality of times, it can be administered or ingested, for example, 1 to several times a day, for example, 1, 2, or 3 times a day, every day or every several days, for example, every 1, 2, 3, or 7 days. The period of administration or ingestion is not limited, and, for example, it can be administered or ingested for 1 week or more, preferably 4 weeks or more, more preferably 8 weeks or more. There can also be a period of discontinuation of administration or ingestion. In certain embodiments, the composition of the present disclosure is administered or ingested for at least 8 weeks. In certain embodiments, the composition of the present disclosure is administered or ingested every day.

[0058] The composition of the present disclosure can be used alone, or can also be used in combination with one or more other ingredients. The "combination use" of ingredients means not only the use of a dosage form containing all the ingredients and the combination of dosage forms containing each ingredient separately, but also means the simultaneous administration or ingestion of each ingredient, or the delayed administration or ingestion of any ingredient, as long as they are used for the same purpose. Two or more other ingredients can also be used in combination. For example, a composition containing one or more other ingredients in addition to asparagus extract can also be used. Ingredients suitable for combination use include diuretics, vasodilators, vitamin agents, steroid agents, anti-dizziness agents, ginkgo biloba extract, bee larva extract, Chinese medicine.

[0059] In addition to the administration or ingestion of asparagus extract, a medical practice other than drug therapy, such as tinnitus retraining therapy, the use of a hearing aid, cochlear implant surgery, and the like, can also be performed.

[0060] In certain embodiments, a method for the treatment and / or prevention of a hearing disorder is provided, comprising administering an effective amount of asparagus extract to a subject in need of treatment and / or prevention of a hearing disorder.

[0061] In some aspects, an asparagus extract is provided for use in the treatment and / or prevention of a hearing disorder.

[0062] In some aspects, an asparagus extract is provided for use in the treatment and / or prevention of a hearing disorder.

[0063] In some aspects, an asparagus extract is provided for use in the preparation of a composition for the treatment and / or prevention of a hearing disorder.

[0064] In some aspects, a method for maintaining and / or improving hearing function is provided, comprising administering an asparagus extract to a subject in need of maintaining and / or improving hearing function.

[0065] In some aspects, an asparagus extract is provided for use in the preparation of a composition for the treatment and / or prevention of a hearing disorder.

[0066] In some aspects, an asparagus extract is provided for use in the preparation of a composition for the treatment and / or prevention of a hearing disorder.

[0067] In some aspects, an asparagus extract is provided for use in the preparation of a composition for the treatment and / or prevention of a hearing disorder.

[0068] For example, the following embodiments are provided.

[0069] [1] A composition for the treatment and / or prevention of a hearing disorder, comprising an asparagus extract.

[0070] [2] The composition according to item 1, wherein the hearing disorder is hearing loss or tinnitus.

[0071] [3] The composition according to item 1, wherein the hearing disorder is presbycusis, noise-induced hearing loss, or tinnitus.

[0072] [4] The composition according to any one of items 1 to 3, wherein the hearing disorder is presbycusis.

[0073] [5] The composition according to any one of items 1 to 3, wherein the hearing disorder is tinnitus.

[0074] [6] The composition according to item 5, wherein the tinnitus is tinnitus classified as mild or moderate in the Tinnitus Handicap Inventory (THI).

[0075] [7] A composition for the maintenance and / or improvement of hearing function, comprising an asparagus extract.

[0076] [8] The composition according to any one of items 1 to 7, which is a pharmaceutical composition, a quasi-pharmaceutical composition, or a food composition.

[0077] [9] The composition according to any one of items 1 to 8, wherein 50 mg to 2000 mg of the asparagus extract is ingested per day.

[0078]

[10] The composition according to any one of items 1 to 9, which is ingested daily for at least 8 weeks.

[0079]

[11] The composition according to any one of items 1 to 10, wherein the asparagus extract is produced by a production method comprising a hot water extraction process on asparagus.

[0080]

[12] The composition according to item 11, wherein the production method further comprises an enzyme treatment on the product of the hot water extraction process.

[0081]

[13] The composition according to any one of items 1 to 12, wherein the asparagus extract is an asparagus stem extract.

[0082] Example

[0083] Manufacture of asparagus officinalis extract

[0084] An asparagus extract was produced by the following method: 1430 L of water was added to chopped green asparagus stems (fresh weight 1100 kg), and pressure sterilization (121°C, 45 minutes) was performed for a hot water extraction process. After cooling to 55°C, 16.5 kg of cellulase (Sucrase C, Mitsubishi Chemical Corporation) was added, and enzyme treatment was performed at 58°C for 1 hour. After further cooling to 45°C, 11 kg of pectinase (Mascelo Team A, Yakult Pharmaceutical Industry Co., Ltd.) was added, and enzyme treatment was performed at 48°C for 24 hours. Then, the enzymes were inactivated by heat treatment (100°C, 20 minutes), and after centrifugal separation using a centrifugal separator, concentration was performed using a concentration machine, and 320 kg of concentrated liquid was recovered. To this concentrated liquid, 50 kg of excipient (Pindex, Matsutani Chemical Industry Co., Ltd.) was added, and pressure sterilization (121°C, 45 minutes) was performed. Then, by spray drying, 125 kg of asparagus extract was obtained.

[0085] Study on hearing improvement effect using a mouse model of presbycusis

[0086] Ten-week-old male C57BL / 6J mice (SPF) (Charles River Laboratories Japan, Inc.) were used (12 mice per course). A 5-day pre-feeding period was set for the first course, a 6-day pre-feeding period was set for the second course, and a 7-day pre-feeding period was set for the third course. During this period, three body weight measurements, one ABR examination, and one observation of general state per day were performed, and animals with no abnormalities in body weight change, auditory brainstem response (ABR) examination, and general state were used for grouping.

[0087] After excluding the two cases with the highest sum of sound pressure thresholds at 16, 24, and 32 kHz in the ABR examination on the last day of the pre-feeding period of each course (in the case of three or more, excluded in order from the highest sound pressure threshold at 32 kHz), grouping was performed by random selection in such a manner that the average and variance of the body weight of each group were approximately equal.

[0088] From the day of animal acquisition until grouping, feed (CRF-1, Oriental Yeast Co., ltd.) was placed in a feeder, and the animals were allowed to freely ingest it. After grouping, control feed (Group 1: CRF-1) and test feed (Group 2: CRF-1 containing 0.26% asparagus extract) were placed in the feeder, and the animals were allowed to freely ingest it. Asparagus is known to contain aspartic acid, which functions as a neurotransmitter, but CRF-1 contains 1.93 g / 100 g of aspartic acid, and the asparagus extract of the present application contains only a trace amount of aspartic acid, so even if 0.26% asparagus extract is added to CRF-1, the amount of aspartic acid hardly changes. The feed in the feeder was replaced with new feed at a frequency of once a week or more. The administration period was 12 weeks (85 days). The general state was observed once a day in the morning.

[0089] Auditory brainstem response (ABR) examination

[0090] ABR examination was performed before administration (at 12 weeks of age), at 8 and 12 weeks after administration (at 20 and 24 weeks of age). Using a disposable syringe made of polypropylene (Terumo Corporation.) equipped with a 25G injection needle (Terumo Corporation.), a mixed anesthetic [ketamine hydrochloride (75 mg / kg) and xylazine hydrochloride (10 mg / kg)] was subcutaneously administered on the back (administration liquid amount: 2 mL / kg). After anesthesia, an active electrode was installed near the external ear of the test ear (right ear), a reference electrode was installed subcutaneously on the top of the head, and a ground electrode was installed subcutaneously on the back of the neck. The potential of ABR was guided from the electrodes to a biological potential amplifier (model: ER-1, Cygnus Technology Inc.), and recorded in a data collection and analysis system (Powerlab, Sampling Soft: Labchart ver. 8, Adinstruments) (recording conditions: sampling time: 10 ms, sampling frequency: 40 kHz, band pass filter: 1-3000 Hz, number of superimpositions 500 times). Regarding the sound stimulus, a coupler type speaker (model: ES1spc, Bio Research Center Co., Ltd) was inserted into the right external auditory canal, and a TDT sound system (ZBus for system3, Tucker-Davis Technologies Inc.) was used to generate (sound pressure range: 10-90 dB, sound types: short tone bursts of 16, 24, and 32 kHz). First, 90 dB of sound stimulus was applied, and ABR was recorded. Thereafter, the sound pressure was appropriately changed, and the maximum sound pressure at which the waveform of ABR disappeared and the minimum sound pressure at which the waveform of ABR was detected were confirmed at 5 dB intervals. The minimum sound pressure at which the waveform of ABR was detected was taken as the sound pressure threshold (ABR thresholds; dB SPL). Note that, in the case where the waveform of ABR was not detected by 90 dB of sound stimulus, the sound pressure threshold was set to 95 dB SPL.

[0091] Statistical methods

[0092] The average and standard error were calculated for the sound pressure threshold at each time point for each group. Regarding the significant difference test for the sound pressure threshold, the Wilcoxon Signed-Rank Test was performed between before administration (Pre) and 6 weeks and 12 weeks after administration in the control group, and it was confirmed that presbycusis occurred. Further, the Wilcoxon Signed-Rank Test was performed at each time point between the control group and the test food group. The significance level was set to 5%. The significant difference test was performed using a commercially available statistical program (SAS System, SAS Institute Japan Corporation) : p < 0.01).

[0093] The results of the ABR test are shown in Table 1. FIG. 1 In the control group, hearing decreased with age when a sound stimulus of 32 kHz was applied, but maintenance of hearing was confirmed in the test food group. This result indicates that the asparagus extract is effective for the prevention and treatment of presbycusis.

[0094] Effect of asparagus officinalis extract intake on tinnitus generation in healthy subjects

[0095] The effect of intake of asparagus extract on tinnitus in healthy adult men and women was investigated by a randomized placebo-controlled double-blind parallel group comparison test.

[0096] Healthy Japanese men and women aged 20 years or older who had a self-perceived symptom of tinnitus and scored 18 or more and 56 or less (mild or moderate tinnitus) on the Japanese version of THI (Tinnitus Handicap Inventory; THI-J, Wakabayashi S, Oishi N, Shinden S, et al. Factor analysis and evaluation of each item of the tinnitus handicap inventory. Head Face Med. 2020; 16(1): 1-9) were enrolled in this test.

[0097] The test food group (asparagus extract food group) was a granular food 1.84 g containing 150 mg of asparagus extract, and the placebo group was a granular food 1.84 g obtained by replacing the asparagus extract with corn starch, caramel pigment, and dextrin. The intake was once a day for 8 weeks. Note that these foods were foods containing a sweetener, an acidifier, a spice, and silicon oxide in addition to the above.

[0098] THI-J was performed before the intake of the test food, 4 weeks after the start of the intake, and 8 weeks after the start of the intake, and the state of tinnitus was evaluated based on the total score. The results are shown in Table 2. FIG. 2 .FIG. 2 The average ± SEM of the total score of THI-J in the test food group and the placebo group is shown. Analysis was performed with a generalized linear mixed model (fixed values: group, time point, interaction of group and time point, covariate: baseline value) : p < 0.01).

[0099] The observed value of the total score of THI-J at the examination after 8 weeks of intake showed a significantly lower value in the test food group than in the placebo group. THI is a questionnaire used in the world to examine the burden caused by tinnitus, and the Japanese translation version was verified for appropriateness and reliability (Wakabayashi S, et al., 2020, supra). The higher the THI score, the higher the disability grade of tinnitus, and it is judged as mild at 18 to 36 points, moderate at 38 to 56 points, and severe at 58 to 100 points. It is known that the minimum change of 6 to 7 points is determined as clinically improved in the total score of THI (Japan Audiology Society, Tinnitus Diagnosis and Treatment Guidelines 2019 Edition, Kinobunko, pp. 7-61; Zeman F, Koller M, Figueiredo R, et al. Tinnitus Handicap Inventory for Evaluating Treatment Effects. Otolaryngol Neck Surg. 2011; 145(2): 282-7). The observed value of the total score of THI-J after 8 weeks of intake was -10.9 points (95% CI [-17.7, -4.2) between groups, and the amount of change before and after the intervention was -14.8 ± 12.8 points in the test food group and -3.9 ± 10.5 points in the placebo group, and the difference between groups was -10.9 points (95% CI [-17.7, -4.2). The amount of change in the total score of THI-J before and after the intervention exceeded 7 points only in the test food group, and the difference between groups after 8 weeks of intake exceeded 7 points, so the significant difference between groups was a clinically meaningful difference. This result indicates that asparagus extract is effective for the prevention and treatment of tinnitus.

[0100] Industrial applicability

[0101] The present application relates to the treatment and / or prevention of hearing disorders, or the maintenance and / or improvement of hearing function, which can be utilized in the medical or food fields.

Claims

1. A composition for treating and / or preventing a hearing disorder, comprising an extract of Asparagus officinalis.

2. The composition of claim 1, wherein, The hearing disorder is hearing loss or tinnitus.

3. The composition of claim 1, wherein, The hearing disorder is presbycusis, noise-induced hearing loss, or tinnitus.

4. The composition of claim 1, wherein, The hearing disorder is presbycusis.

5. The composition of claim 1, wherein, The hearing disorder is tinnitus.

6. The composition of claim 5, wherein, The tinnitus is tinnitus classified as mild or moderate in the Tinnitus Handicap Inventory (THI).

7. A composition for maintaining and / or improving auditory function, comprising an extract of Asparagus officinalis.

8. The composition according to any one of claims 1 to 7, which is a pharmaceutical composition, quasi-pharmaceutical composition, or food composition.

9. The composition according to any one of claims 1 to 8, wherein, 50 mg to 2000 mg of the extract of Asparagus officinalis is ingested per day.

10. The composition according to any one of claims 1 to 9, which is ingested daily for at least 8 weeks.

11. The composition according to any one of claims 1 to 10, wherein, The extract of Asparagus officinalis is manufactured by a manufacturing method comprising a hot water extraction process on Asparagus officinalis.

12. The composition of claim 11, wherein, The manufacturing method further comprises an enzyme treatment on the product of the hot water extraction process.

13. The composition according to any one of claims 1 to 12, wherein, The extract of Asparagus officinalis is an extract of Asparagus officinalis stem.

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