Composition for treating and / or preventing hearing impairment

Abstract

Provided is: a composition for treating and / or preventing hearing impairment, the composition containing an asparagus extract; or a composition for maintaining and / or improving hearing function, the composition containing an asparagus extract.

Description

Composition for the treatment and / or prevention of hearing impairment

[0001] This patent application claims priority to Japanese Patent Application No. 2023-104149, the entire contents of which are incorporated herein by reference. The present disclosure relates to compositions for treating and / or preventing hearing impairment, or compositions for maintaining and / or improving hearing function.

[0002] The World Health Organization (WHO) reports that over one billion young people are at risk of noise-induced hearing loss due to exposure to loud noise for purposes such as listening to music. Age-related hearing loss is considered a major risk factor for dementia, and hearing loss prevention is also important as a dementia prevention measure. Noise-induced and age-related hearing loss are thought to occur when hair cells in the inner ear are gradually damaged by noise and aging. Because 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 even in the absence of acoustic stimulation, and tinnitus and its associated symptoms cause a significant psychological burden. Hearing loss is thought to be one of the triggering factors for tinnitus.

[0003] Asparagus is a vegetable produced and consumed in many countries and has been found to have various physiological activities. For example, it is known that asparagus stem extracts have preventive and recovery effects against various types of fatigue (such as physical fatigue and fatigue due to mental stress) and brain function improving effects, and that asparagus pseudo-leaf extracts have autonomic nervous system regulating effects. Patent Document 1 describes that hydroxymethylfurfural derivatives derived from hot water-heat-treated asparagus have excellent HSP-inducing activity, anti-stress effects, and autonomic nervous system regulating effects. However, the effects of asparagus extracts on hearing impairment or hearing function are unknown.

[0004] International Publication No. 2013 / 094676

[0005] The present disclosure aims to provide methods for treating and / or preventing hearing impairment, or for maintaining and / or improving hearing function.

[0006] The present inventors have found that asparagus extract is effective in improving hearing loss and tinnitus. Thus, in one aspect, the present disclosure provides a composition for treating and / or preventing hearing impairment, comprising an asparagus extract. In another aspect, the present disclosure provides a composition for maintaining and / or improving hearing function, comprising an asparagus extract.

[0007] The present disclosure provides new means for treating and / or preventing hearing impairment, or for maintaining and / or improving hearing function.

[0008] Figure 1 shows the results of an ABR test in which a 32 kHz sound stimulus was applied to a mouse model of age-related hearing loss fed a control feed or a test feed containing asparagus extract. Figure 2 shows the total THI scores for the asparagus extract group and the placebo group in a clinical trial investigating the effect of asparagus extract intake on tinnitus in healthy subjects.

[0009] Unless otherwise specified, terms used herein have the meanings commonly understood by those skilled in the art of organic chemistry, medicine, pharmacology, molecular biology, microbiology, etc. Definitions of some terms used herein are provided below, but these definitions take precedence over common understandings in this specification.

[0010] As used herein, when a numerical value is accompanied by the term "about," it is intended to encompass a range of ±10% of that value. For example, "about 20" is intended to include "18 to 22." A range of numerical values ​​includes all values ​​between and at the endpoints. "About" in reference to a range applies to both endpoints of the range. Thus, for example, "about 20 to 30" is intended to include "18 to 33."

[0011] The asparagus extract of the present disclosure is a mixture of asparagus-derived components contained in a liquid obtained by hot water extraction of asparagus and removing the residue. The raw material for the asparagus extract is preferably the stem (asparagus stalk) of asparagus (Asparagus officinalis), including young stems and leaves. The undercut portion of asparagus stalks, which is discarded for reasons such as the efficiency of harvesting, transporting, or selling edible asparagus, may also be used. The raw material for the asparagus extract may be, for example, fresh asparagus, dried asparagus, or dried and powdered asparagus. Examples of asparagus include green asparagus, white asparagus, and purple asparagus, with green asparagus being preferred. The origin of the asparagus is not particularly limited.

[0012] The method for producing an asparagus extract of the present disclosure includes a step of subjecting asparagus to a hot water extraction treatment. "Hot water extraction treatment" means heating the raw material in hot water to extract components contained in the raw material into the water. The step of subjecting asparagus to a hot water extraction treatment is carried out, for example, by adding 1 to 50 times the amount of water to the asparagus and heating it in hot water for 20 to 180 minutes. The temperature at this time is preferably, for example, 50 to 300°C. When hot water extraction treatment is carried out under atmospheric pressure, a temperature of, for example, 90°C or higher is preferred. The hot water extraction treatment may also be carried out under pressure, preferably at a pressure of, for example, 0.1 to 0.2 MPa (for example, 0.12 MPa when using an autoclave).

[0013] The method for producing an asparagus extract of the present disclosure may further include the additional steps exemplified below for the purpose of increasing the efficiency of the hot water extraction step.

[0014] An additional step may be, for example, shredding the asparagus before the hot water extraction treatment. The asparagus can be shredded to a size of, for example, about 0.1 to 10 cm. The shredding may be done manually using, for example, a knife or cutter, or may be done using a machine such as a shredder or mill.

[0015] An additional step may include, for example, pressing the asparagus prior to the hot water extraction process. The asparagus may be pressed, for example, using a press.

[0016] An example of an additional step is an enzyme treatment step performed before or after the hot water extraction step, for example, to disrupt plant tissue. The enzyme treatment can further increase the efficiency of the hot water extraction step. For example, enzymes such as cellulase, hemicellulase, pectinase, amylase, and pullulanase, or a combination of two or more of these enzymes, are preferably used to efficiently decompose fibrous substances, pectin, and the like, in asparagus. In the enzyme treatment step, the most appropriate addition amount, temperature, and reaction time for the enzyme used can be selected. When cellulase is used, for example, the enzyme treatment can be performed at a temperature of 30 to 60°C for 1 to 72 hours, with an addition amount of cellulase of 0.1 to 5% (w / w). When pectinase is used, for example, the enzyme treatment can be performed at a temperature of 30 to 60°C for 1 to 72 hours, with an addition amount of pectinase of 0.1 to 10% (w / w). The enzymatic treatment step may be carried out before or after the hot water extraction step, and is preferably carried out after the hot water extraction step with cellulase and / or pectinase.

[0017] An example of an additional step is mechanically pulverizing the residue after the hot water extraction treatment. For pulverization, a machine such as a mill or a mixer may be used.

[0018] Additional steps include, for example, centrifugal separation or filtration after the hot water extraction treatment. By further including these steps, residues can be efficiently removed to obtain a heat-treated liquid. Centrifugation can be carried out, for example, at a rotation speed of 3,000 to 7,000 rpm and a temperature of 4 to 50°C. For filtration, for example, commercially available filter paper, filter cloth, etc. can be used.

[0019] An example of an additional step is concentrating the heat-treated liquid obtained after the hot water extraction treatment under reduced pressure. Concentration can be carried out using, for example, an evaporator.

[0020] An additional step may be, for example, spray-drying or freeze-drying the heat-treated liquid after the hot water extraction treatment. Spray-drying may be carried out, for example, at an exhaust air temperature of 70 to 90°C and a chamber temperature of 80 to 100°C. Prior to spray-drying or freeze-drying, an excipient may be added to the heat-treated liquid. Examples of excipients include starch, starch hydrolysates, dextrin, maltodextrin, maltooligosaccharides, lactose, sorbitol, mannitol, and sucrose. Following spray-drying or freeze-drying, the product may be sieved.

[0021] In one embodiment, the method for producing an asparagus extract comprises the following steps: (1) extracting asparagus with hot water to obtain a hot-water extract, (2) treating the hot-water extract with an enzyme to obtain an enzyme-treated product, (3) removing residue from the enzyme-treated product to obtain an enzyme-treated liquid, and (4) concentrating, spray-drying, and / or freeze-drying the enzyme-treated liquid to obtain an asparagus extract.

[0022] In one embodiment, the method for producing an asparagus extract comprises the following steps: (1) treating asparagus with an enzyme to obtain an enzyme-treated product, (2) extracting the enzyme-treated product with hot water to obtain a hot water-extracted product, (3) removing residue from the hot water-extracted product to obtain a heat-treated liquid, and (4) concentrating, spray-drying, and / or freeze-drying the heat-treated liquid to obtain an asparagus extract.

[0023] The following are examples of methods for producing asparagus extract. Production Example 1: Asparagus stalks are shredded to approximately 0.1 to 10 cm lengths, and 1 to 50 times the volume of water is added. Hot water extraction 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) cellulase is added, and enzymatic treatment is performed at 30 to 60°C for 1 to 72 hours. The residue is mechanically pulverized and centrifuged at 3,000 to 7,000 rpm and 4 to 50°C to obtain a supernatant. The supernatant is spray-dried at an exhaust air temperature of 70 to 90°C and a chamber temperature of 80 to 100°C.

[0024] Production Example 2: Asparagus stalks are shredded to approximately 0.1 to 10 cm lengths and 1 to 50 volumes of water are added. Hot water extraction is performed for 20 to 180 minutes at 50 to 100°C or under pressure at 121°C. After cooling, 0.1 to 5% (w / w) cellulase is added and enzyme treatment is performed for 1 to 72 hours at 30 to 60°C. 0.1 to 10% (w / w) pectinase is added and enzyme treatment is performed for 1 to 72 hours at 30 to 60°C. The enzyme is inactivated by heat treatment. The supernatant is obtained by centrifugation at 3,000 to 7,000 rpm and 4 to 50°C. The supernatant is concentrated, excipients are added, and the mixture is autoclaved. The mixture is then spray-dried or freeze-dried at an exhaust air temperature of 70 to 90°C and a chamber temperature of 80 to 100°C.

[0025] Manufacturing Method 3: Dried asparagus stalks are powdered and 1 to 50 times the volume of water is added. Hot water extraction is performed for 20 to 180 minutes at 50 to 100°C or under pressure at 121°C. After cooling, 0.1 to 5% (w / w) cellulase and 0.1 to 10% (w / w) pectinase are added, and enzyme treatment is performed for 1 to 72 hours at 30 to 60°C. The enzymes are inactivated by heat treatment. The supernatant is obtained by centrifugation at 3,000 to 7,000 rpm and 4 to 50°C. The supernatant is concentrated, excipients are added, and the mixture is autoclaved. The mixture is then spray-dried or freeze-dried at an exhaust air temperature of 70 to 90°C and a chamber temperature of 80 to 100°C.

[0026] Typically, the asparagus extract contains no more than 10%, no more than 5%, no more than 4%, no more than 3%, no more than 2%, no more than 1%, no more than 0.5%, no more than 0.3%, or no more than 0.25% aspartic acid.

[0027] As shown in the examples below, the compositions of the present disclosure can treat and / or prevent hearing impairment. In this disclosure, hearing impairment includes hearing loss and tinnitus. In some embodiments, the hearing impairment is not associated with other diseases, such as Meniere's disease.

[0028] Hearing loss is one of the most common sensory disorders and is characterized by a decrease in hearing ability. Hearing loss includes age-related hearing loss, noise-induced hearing loss, and drug-induced hearing loss, especially age-related hearing loss. Examples of noise-induced hearing loss include acoustic hearing loss and occupational hearing loss. Hearing loss can be diagnosed by tests such as pure tone audiometry, speech audiometry, word recognition score, tympanometry, and acoustic reflex.

[0029] Tinnitus is the perception of sound in the absence of a sound stimulus. Tinnitus can be assessed, for example, by the Tinnitus Distress Inventory (THI). The THI consists of 25 questions, and subjects select an answer from "often (4 points)," "sometimes (2 points)," or "never (0 points)" for each item, and the total score determines the degree of tinnitus distress. The original version of the THI is in English, but it has been translated into multiple languages, including Japanese, and its validity and reliability have been verified. The higher the THI score, the greater the degree of tinnitus distress, with 18-36 being considered mild, 38-56 being considered moderate, and 58-100 being considered severe. In some embodiments, the tinnitus is tinnitus that is considered mild or moderate on the THI.

[0030] As used herein, "treat" or "treatment" means slowing or halting the progression of hearing impairment and / or reducing, alleviating, ameliorating or eliminating hearing impairment in a subject with hearing impairment.

[0031] In the present disclosure, "preventing" or "prevention" refers to preventing the onset of hearing impairment or reducing the likelihood of developing hearing impairment in a subject, particularly in a subject who may develop hearing impairment but has not yet done so. Subjects who may develop hearing impairment but have not yet done so include subjects with risk factors for hearing impairment. Risk factors for hearing impairment include, for example, advanced age (e.g., age 50 or older, 55 or older, 60 or older, 65 or older, 70 or older, or 75 or older), exposure to noise or loud sounds, changes in air pressure, stress, earwax accumulation, impaired blood flow to the inner ear, viral infection, medications (e.g., antibiotics, anticancer drugs, salicylate-based drugs), acoustic neuroma, otitis media (e.g., chronic otitis media, otitis media with effusion), head trauma, autoimmune disease, and genetics.

[0032] The subject for treatment and / or prevention of hearing impairment is an animal, generally a mammal, such as a human, a non-human primate (e.g., a monkey, a gibbon, a chimpanzee, an orangutan, or a macaque), a companion animal (e.g., a dog or a cat), a livestock animal (e.g., a horse, a cow, a goat, a sheep, or a pig), or an experimental 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, but may be, for example, middle-aged or elderly, specifically, 50 years or older, 55 years or older, 60 years or older, 65 years or older, 70 years or older, or 75 years or older. In some embodiments, the subject does not suffer from Meniere's disease.

[0033] As shown in the examples below, the compositions of the present disclosure can maintain and / or improve hearing function. In the present disclosure, maintaining hearing function includes maintaining hearing acuity and preventing its decline. Improving hearing function includes improving hearing acuity, maintaining an improved state, and preventing its decline from an improved state. Hearing acuity can be measured by pure-tone audiometry.

[0034] The subject for maintaining and / or improving hearing function is an animal, generally a mammal, such as a human, a non-human primate (e.g., a monkey, a gibbon, a chimpanzee, an orangutan, or a macaque), a companion animal (e.g., a dog or a cat), a livestock animal (e.g., a horse, a cow, a goat, a sheep, or a pig), or an experimental 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, but may be, for example, middle-aged or elderly, specifically, 50 years or older, 55 years or older, 60 years or older, 65 years or older, 70 years or older, or 75 years or older. The subject may or may not have a hearing impairment. In some embodiments, the subject does not suffer from Meniere's disease.

[0035] The composition of the present disclosure may be a pharmaceutical composition or a quasi-drug composition. The asparagus extract can be prepared by conventional methods into dosage forms such as tablets, granules, powders, capsules, syrups, and injections. Furthermore, excipients, binders, lubricants, colorants, disintegrants, thickeners, preservatives, stabilizers, pH adjusters, and the like commonly used in pharmaceuticals can be added. The method of administration of the pharmaceutical composition or quasi-drug composition is not particularly limited, and may be, for example, oral administration, intravenous administration, intraperitoneal administration, intradermal administration, or sublingual administration, with oral administration being preferred.

[0036] The composition of the present disclosure may also be a food composition. The food composition may be in the form of a typical processed food, such as a solid food or a liquid food such as a beverage, a drinkable supplement, a powdered beverage, or a soup. The food composition may be consumed, for example, as juice, confectionery, jelly, tablet, dressing, or seasoning. The food composition may be produced by processing the asparagus extract using a conventional method into a form suitable for consumption, such as granules, particles, tablets, capsules, gels, creams, pastes, suspensions, aqueous solutions, emulsions, or powders. Additionally, excipients, binders, lubricants, colorants, disintegrants, thickeners, preservatives, stabilizers, pH adjusters, and the like commonly used in foods may be added. Furthermore, sugars, sugar alcohols, salts, oils and fats, amino acids, organic acids, glycerin, and the like may be added to improve the taste. The asparagus extract may also be incorporated into existing foods; the base food is not particularly limited.

[0037] Such foods may also be provided as health functional foods or dietary supplements. Health functional foods include, for example, foods for specified health uses, foods with nutrient functions, and foods with functional claims. Health functional foods can be labeled as being used for purposes such as maintaining and / or improving hearing function. The labeling may be directly displayed on the packaging, container, label, tag, attached documents, etc., accompanying the product, or indirectly displayed through advertising and promotional activities. Dietary supplements include, for example, nutritional supplements and health supplements.

[0038] The dosage and administration method, or the amount and administration method of the composition, are not particularly limited. These dosages can be determined taking into consideration the subject's gender, age, body weight, overall health condition, pathological condition, and the like. For example, the dosage or intake of the composition of the present disclosure can be 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 mg to 190 mg, about 120 mg to 180 mg, about 130 mg to 170 mg, about 140 mg to 160 mg, or about 145 mg to 155 mg of asparagus extract administered or ingested per day, for example, about 150 mg. The daily dosage or intake of asparagus extract may be contained in a single composition, or may be distributed across multiple compositions administered or ingested per day.

[0039] The compositions of the present disclosure may be administered or ingested once or multiple times. When administered or ingested multiple times, for example, they may be administered or ingested once to several times a day, for example, once, twice, or three times a day, daily or every few days, for example, every 1, 2, 3, or 7 days. The period of administration or ingestion is not limited, and for example, they may be administered or ingested continuously for one week or more, preferably four weeks or more, and more preferably eight weeks or more. There may be a period during which administration or ingestion is discontinued. In one embodiment, the compositions of the present disclosure are administered or ingested for at least eight weeks. In one embodiment, the compositions of the present disclosure are administered or ingested daily.

[0040] The compositions of the present disclosure may be used alone or in combination with one or more additional ingredients. "Combined use" of ingredients refers not only to the use of a dosage form containing all ingredients or the use of a combination of dosage forms containing each ingredient separately, but also to the simultaneous administration or ingestion of each ingredient or delayed administration of any of the ingredients, as long as they are used for the same purpose. Two or more additional ingredients may also be used in combination. For example, a composition containing one or more additional ingredients in addition to asparagus extract may be used. Ingredients suitable for combination use include diuretics, vasodilators, vitamins, steroids, antidizziness agents, ginkgo biloba extract, bee larvae extract, and herbal medicines.

[0041] In addition to administering or consuming asparagus extract, non-pharmacological medical interventions such as tinnitus retraining therapy, use of hearing aids, cochlear implant surgery, etc. may also be performed.

[0042] In one aspect, a method for treating and / or preventing hearing impairment is provided, comprising administering an effective amount of an asparagus extract to a subject in need thereof. In one aspect, an asparagus extract is provided for treating and / or preventing hearing impairment. In one aspect, a use of an asparagus extract for treating and / or preventing hearing impairment is provided. In one aspect, a use of an asparagus extract in the manufacture of a composition for treating and / or preventing hearing impairment is provided.

[0043] In one aspect, a method for maintaining and / or improving hearing function is provided, comprising administering an asparagus extract to a subject in need thereof. In one aspect, an asparagus extract for maintaining and / or improving hearing function is provided. In one aspect, a use of an asparagus extract for maintaining and / or improving hearing function is provided. In one aspect, a use of an asparagus extract for maintaining and / or improving hearing function is provided. In one aspect, a use of an asparagus extract in the manufacture of a composition for maintaining and / or improving hearing function is provided.

[0044] For example, the following embodiments are provided: [1] A composition for treating and / or preventing hearing impairment, comprising an asparagus extract. [2] The composition according to item 1, wherein the hearing impairment is hearing loss or tinnitus. [3] The composition according to item 1, wherein the hearing impairment is age-related hearing loss, noise-induced hearing loss, or tinnitus. [4] The composition according to any of items 1 to 3, wherein the hearing impairment is age-related hearing loss. [5] The composition according to any of items 1 to 3, wherein the hearing impairment is tinnitus. [6] The composition according to item 5, wherein the tinnitus is tinnitus classified as mild or moderate in the Tinnitus Distress Inventory (THI). [7] A composition for maintaining and / or improving hearing function, comprising an asparagus extract. [8] The composition according to any of items 1 to 7, which is a pharmaceutical composition, a quasi-drug composition, or a food composition. [9] The composition according to any of items 1 to 8, wherein 50 mg to 2,000 mg of the asparagus extract is ingested daily.

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

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

[12] The composition according to item 11, wherein the process further comprises enzymatically treating the product of the hot water extraction.

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

[0045] Preparation of Asparagus Extract: An asparagus extract prepared by the following method was used: 1,430 L of water was added to shredded green asparagus stalks (1,100 kg fresh weight), and the mixture was autoclaved (121°C, 45 minutes) for the purpose of hot water extraction. After cooling to 55°C, 16.5 kg of cellulase (sucrase C, Mitsubishi Chemical Corporation) was added, and enzyme treatment was carried out at 58°C for 1 hour. After further cooling to 45°C, 11 kg of pectinase (Maceroteam A, Yakult Pharmaceutical Industry Co., Ltd.) was added, and enzyme treatment was carried out at 48°C for 24 hours. The enzyme was then inactivated by heat treatment (100°C, 20 minutes), centrifuged, and concentrated using a concentrator to recover 320 kg of concentrate. 50 kg of excipient (Pinex, Matsutani Chemical Industry Co., Ltd.) was added to this concentrate, and the mixture was autoclaved (121°C, 45 minutes). 125 kg of asparagus extract was then obtained by spray drying.

[0046]

[0046] 10-week-old male C57BL / 6J mice (SPF) (Charles River Japan, Inc.) were used (12 mice per cycle). A preliminary breeding period of 5 days for the first cycle, 6 days for the second cycle, and 7 days for the third cycle was set. During this period, weight measurements were taken three times, general condition observations were made once a day, and an ABR test was performed once. Animals showing no abnormalities in weight change, auditory brainstem response (ABR) tests, or general condition were used for group allocation.

[0047] For each course, the two animals with the highest sum of sound pressure thresholds at 16, 24, and 32 kHz in the ABR test on the last day of the preliminary breeding period were excluded (if there were three or more, they were excluded in order of highest sound pressure threshold at 32 kHz), and then the animals were divided into groups using random sampling so that the mean and variance of body weight in each group were approximately equal.

[0048] From the day of animal acquisition until group assignment, the animals were provided with a feeder containing CRF-1 (Oriental Yeast Co., Ltd.) and allowed to consume the feed ad libitum. After group assignment, the animals were provided with a control feed (Group 1: CRF-1) and a test feed (Group 2: CRF-1 containing 0.26% asparagus extract) and allowed to consume the feeder ad libitum. Asparagus is known to contain aspartic acid, which acts as a neurotransmitter, CRF-1 contains 1.93 g / 100 g of aspartic acid. Since the amount of aspartic acid contained in the asparagus extract of the present invention is very small, adding 0.26% asparagus extract to CRF-1 did not significantly affect the amount of aspartic acid. The feeder was replaced with fresh feed at least once a week. The administration period was 12 weeks (85 days). The animals were observed for general condition once daily in the morning.

[0049] Auditory brainstem response (ABR) testing was performed before administration (12 weeks of age) and 8 and 12 weeks after administration (20 and 24 weeks of age). A mixed anesthetic [ketamine hydrochloride (75 mg / kg) and xylazine hydrochloride (10 mg / kg)] was administered subcutaneously to the back (volume: 2 mL / kg) using a disposable polypropylene syringe (Terumo Corporation) equipped with a 25G needle (Terumo Corporation). After anesthesia, a sensitive electrode was placed near the outer ear of the right ear, an indifferent electrode was placed subcutaneously on the vertex, and a ground electrode was placed subcutaneously on the back of the neck. The ABR potential was transferred from the electrodes to a biopotential amplifier (Model: ER-1, Cygnus Technology Inc.) and recorded on a data acquisition and analysis system (PowerLab, sampling software: LabChart ver. 8, ADInstruments) (recording conditions: sampling time: 10 ms, sampling rate: 40 kHz, bandpass filter: 1-3000 Hz, summation count: 500). Sound stimuli were delivered via a Coupler-type speaker (Model: ES1spc, BioResearch Center Co., Ltd.) inserted into the right ear canal using a TDT acoustic system (ZBus for system 3, Tucker-Davis Technologies Inc.) (sound pressure range: 10-90 dB, sound type: 16, 24, and 32 kHz tone burst). A 90 dB sound stimulus was first applied to record the ABR. The sound pressure was then adjusted appropriately, and the maximum sound pressure at which the ABR waveform disappeared and the minimum sound pressure at which the ABR waveform was detected were confirmed in 5 dB increments. The minimum sound pressure at which the ABR waveform was detected was defined as the sound pressure threshold (dB SPL). Note that when the ABR waveform was not detected with a 90 dB sound stimulus, the sound pressure threshold was set to 95 dB SPL.

[0050] Statistical methods: Mean values ​​and standard errors were calculated for sound pressure thresholds at each time point for each group. A Wilcoxon signed rank sum test was performed to test for significant differences in sound pressure thresholds between the control group at Pre and 6 and 12 weeks after administration, confirming the occurrence of age-related hearing loss. Furthermore, a Wilcoxon rank sum test was performed at each time point between the control group and the test feed group. The significance level was set at 5%. The significance test was performed using a commercially available statistical program (SAS system, SAS Institute Japan Co., Ltd.) ( ＊＊ : p<0.01).

[0051] The results of the ABR test are shown in Figure 1. When a 32 kHz sound stimulus was given, hearing ability declined with age in the control group, but hearing ability was maintained in the test diet group. This result suggests that asparagus extract is effective in preventing and treating age-related hearing loss.

[0052] Effect of asparagus extract intake on tinnitus in healthy individuals A randomized, placebo-controlled, double-blind, parallel-group comparative study was conducted to examine the effect of asparagus extract intake on tinnitus in healthy adult men and women.

[0053] Healthy Japanese men and women aged 20 years or older with subjective tinnitus symptoms and a score of 18 to 56 (mild or moderate tinnitus) on the Japanese version of the 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 study.

[0054] The test food group (asparagus extract group) ingested 1.84 g of a granular food containing 150 mg of asparagus extract, and the placebo group ingested 1.84 g of a granular food in which the asparagus extract was replaced with cornstarch, caramel coloring, and dextrin, once daily for eight weeks.In addition to the above, these foods also contained sweeteners, acidulants, flavorings, and silicon oxide.

[0055] THI-J was administered before ingestion of the test food, and 4 and 8 weeks after the start of ingestion, and the state of tinnitus was evaluated by the total score. The results are shown in Figure 2. Figure 2 shows the mean ± SEM of the total score in the test food group and the placebo group. Analysis was performed using a general linear mixed model (fixed values: group, time point, interaction between group and time point, covariate: baseline value) ( ＊＊ : p<0.01).

[0056] The THI-J total score measured after 8 weeks of intake was significantly lower in the test food group than in the placebo group. The THI is a questionnaire used worldwide to assess tinnitus burden, and the Japanese translation has been validated for validity and reliability (Wakabayashi S, et al., 2020, supra). Higher THI scores indicate greater tinnitus distress, with scores of 18-36 representing mild, 38-56 representing moderate, and 58-100 representing severe. The minimum change in THI total score required to be considered clinically improved is known to be 6-7 points (Japan Audiology Society, Tinnitus Management Guidelines 2019, Kanehara Publishing, 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 difference between the groups in the actual THI-J total score after 8 weeks of intake was -10.9 points (95% CI [-17.7, -4.2]), and the change from before to after intervention was -14.8 ± 12.8 points for the test food group and -3.9 ± 10.5 points for the placebo group, resulting in a difference between the groups of -10.9 points (95% CI [-17.7, -4.2]). The test food group was the only group whose THI-J total score changed by more than 7 points from before to after intervention, and the difference between the groups after 8 weeks of intake exceeded 7 points, making this significant difference clinically meaningful. These results suggest that asparagus extract is effective in preventing and treating tinnitus.

[0057] The present disclosure relates to the treatment and / or prevention of hearing impairment, or the maintenance and / or improvement of hearing function, and may be used in the fields of medicine or food.

Claims

1. A composition for the treatment and / or prevention of hearing impairment comprising an asparagus extract.

2. The composition according to claim 1, wherein the hearing impairment is hearing loss or tinnitus.

3. The composition according to claim 1, wherein the hearing impairment is age-related hearing loss, noise-induced hearing loss or tinnitus.

4. The composition according to claim 1, wherein the hearing impairment is age-related hearing loss.

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

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

7. A composition for maintaining and / or improving hearing function comprising an asparagus extract.

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

9. The composition according to any one of claims 1 to 8, wherein 50 mg to 2000 mg of asparagus extract is ingested daily.

10. The composition of any one of claims 1 to 9, wherein the composition is taken daily for at least 8 weeks.

11. The composition according to any one of claims 1 to 10, wherein the asparagus extract is produced by a process including subjecting asparagus to hot water extraction treatment.

12. The composition of claim 11, wherein the process further comprises enzymatically treating the product of the hot water extraction treatment.

13. The composition according to any one of claims 1 to 12, wherein the asparagus extract is an asparagus stalk extract.

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