KR101818395B1 - Composition for preventing or treating hearing loss - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for prevention or treatment of hearing loss or a food composition for preventing or ameliorating hearing loss comprising onion skin extract or quercetin.

Description

[Composition for preventing or treating hearing loss]

The present invention relates to a pharmaceutical composition for prevention or treatment of deafness, comprising an onion skin extract or quercetin, and a food composition for preventing or ameliorating deafness.

The ears classify the ear canal and the ear canal into the outer ear, the eardrum and ossicles in the middle ear, and the cochlea and the auditory nerve in the inner ear. Sound is acoustical energy transmitted through the auricle and external auditory canal to vibrate the eardrum. The vibration of the eardrum is transferred to the ossicles consisting of three small bones attached to the eardrum with mechanical energy. The last bone of the ossicle, the spine, connects to the cochlea, which transfers energy to the lymph fluid in the cochlea. The delivered energy causes the lymphatic fluid to oscillate, which causes the hair cells in the cochlea to be stimulated. As the hair cells move, the neurons are transferred to the auditory nerves attached to the hair cells, and the sound energy is transferred from the auditory nerve to the brain in the form of electrical energy. As an organ that delivers sounds to the outside, it can be recovered by treatment or surgery, and the resulting hearing loss can also be improved after treatment. This hearing loss is called conductive hearing loss. The sensorineural hearing loss, which is caused by a problem in the brain responsible for the hearing that plays a comprehensive role, such as the cochlea, which senses the sound, the auditory nerve transmitting the sound by electric energy, and the discrimination and understanding of sound, do.

Most of the hearing loss is related to sensory neural deafness, which has no treatment method other than prevention until now. Once the hearing loss occurs, it is assisted by using auxiliary means such as hearing aid or by implanting mechanical device into the body. The causes of sensory nerve impairment include noise, drugs, aging, trauma, metabolic diseases, and viruses. Of these, the most notable increase in recent years is hearing loss due to noise and aging. Aging society, a global trend, is increasing the number of senile hearing loss, as well as occupational noise-induced hearing loss, such as workers and soldiers working in noise environments, as well as noise and hearing loss due to cultural and leisure activities.

In recent years, research on pre-clinical studies on antioxidants, N-methyl-D-aspartate (NMDA) antagonists, apoptosis inhibitors, growth factors (Prasher D., Lancet , 352, pp. 1240-1242, 1998). However, there are limitations to proceed to clinical trials. To date, no approved drugs have been approved for the prevention and treatment of noise-induced hearing loss, and studies reported in the academia have shown that Mg, NAC (N-acetylcysteine, NAC) and Ebselen (Meister A., Pharmacol. Ther ., 51, pp 155-194, 1991; Attias J. et al., Am. J. Otolaryngol ., 15, pp26-32, 1994; Yamasoba T. et al. et al., Neurosci . Lett ., 380, pp234-238, 2005).

Under these circumstances, the present inventors have searched for various active substances capable of preventing or treating hearing loss in natural products having excellent safety, and surprisingly found that the onion skin extract and quercetin effectively inhibited the rise of the hearing threshold due to noise , Thereby completing the present invention.

The invention onion (Allium The present invention also provides a pharmaceutical composition for preventing or treating hearing loss comprising cepa peel extract or quercetin.

The present invention also relates to an onion skin ( Allium The present invention also provides a food composition for preventing or ameliorating hearing loss comprising cepa peel extract or quercetin.

To achieve the above object, the present invention provides an onion skin ( Allium The present invention provides a pharmaceutical composition for prevention or treatment of deafness including cepa peel extract or quercetin.

The pharmaceutical composition according to the present invention is effective for the prevention or treatment of hearing loss including all-tone deafness and sensory nerve impairment, and is particularly effective for the prevention of acute traumatic hearing loss, temporary threshold increase due to short- And is effective in preventing or treating the noise-induced hearing loss.

The terms used in the present invention, "onion" is the scientific name Allium quot; cepa " and "onion skin" means the skin of the onion.

For the purposes of the present invention, the onion skin, onion skin extract and quercetin are used for the prevention or treatment of hearing loss.

In the present invention, the onion or onion skin may be purchased commercially or used, or harvested or cultivated in nature, but is not limited thereto.

As used herein, the term "extract" means a substance obtained by separating from onion skin, and specifically includes water, a C _1-4 alcohol (e.g., methanol, ethanol, butanol, etc.) Means a substance obtained by separation using an extraction solvent such as a mixed solvent. Preferably, the onion skin extract of the present invention is an ethanol extract of onion skin.

Specifically, the onion skin extract according to the present invention is prepared by extracting with an extraction solvent, preferably a mixed solvent of water and ethanol, about 1 to 20 times, preferably about 3 to 10 times, the weight of the onion skin .

The mixed solvent may preferably be an aqueous solution of about 70% ethanol. Extraction can be carried out by methods known in the art such as, for example, cold-pressing, hot water extraction, ultrasonic extraction, reflux-cooling extraction, and the like. The extraction temperature can be varied by a person skilled in the art in a variety of temperature ranges suitable for the extraction method, for example, but not limited to, from 20 캜 to 100 캜. Further, the extraction time differs depending on the extraction method, and a person skilled in the art can adopt an appropriate extraction time, but can be performed in a single or multiple cycles in a range of about 1 hour to 10 days, although not limited thereto. Preferably, the extraction can be carried out by extracting with the above-mentioned extraction solvent 2 to 3 times at room temperature for about 2 days.

The term "quercetin" in the present invention means a compound represented by the formula:

The quercetin is a kind of flavonol and is known to be abundant in red wine, onion, especially onion skin, green tea, apple, berry, etc., and is known to have antioxidant and anticancer effects.

The quercetin may be isolated from a natural product (for example, onion skin), purchased commercially or used by a person skilled in the art in a known manner, but is not limited thereto.

As used herein, the term "hearing loss" refers to a condition in which hearing loss is reduced by abnormalities in any of the external, middle, and neurotransmitter pathways, including conductive hearing loss and sensorineural hearing loss. Preferably, in the present invention, the hearing loss is caused by noise induced hearing loss (NIHL), which is a symptom of damage to the cochlea and the auditory nerve due to various types of noise caused by various causes such as noise, drugs, aging, trauma, ). ≪ / RTI >

The noise-induced hearing loss includes both acoustic trauma hearing loss, temporary threshold shift (TTS) due to short-term noise, and permanent threshold shift (PTS) due to long noise .

The onion skin extract or quercetin of the present invention can effectively suppress hearing loss, in particular, acoustic trauma, temporary or permanent noise-induced hearing loss by effectively suppressing the rise of hearing threshold due to noise or the like.

In a specific example, the onion skin extract was administered to the mouse to measure the joint soundness. As a result, it was confirmed that the onion skin extract improved the damage of the cochlea in the cochlea exposed to noise (FIG. 1). In addition, in order to confirm the hearing improvement effect of the onion skin extract, cleavage induced potential measurement was performed on the mouse, and as a result, it was confirmed that the hearing threshold was significantly decreased in both the click sound and the tone burst stimulus sound 3). In addition, it was confirmed that the onion bark extract improves the auditory cortex damage (FIG. 4) as a result of the mid-term test with Na-Pa amplitude.

Further, in another specific experimental example, in order to confirm the hearing improvement effect of quercetin, cleavage evoked potential measurement was performed on a mouse, and as a result, it was confirmed that the hearing threshold was significantly decreased in both the click sound and the tone burst stimulus (Figs. 5 to 7). In addition, quercetin was treated with zebrafish to confirm the improvement effect on neomycin-induced hair cell damages, and as a result, it was confirmed that the number of neurons and hair cells decreased by damage remarkably increased (Fig. 9).

As described above, the onion skin extract or quercetin of the present invention greatly reduces the auditory threshold value and remarkably increases the number of injured neurons and hair cells, thereby alleviating the damage to the auditory pathway, and thus being useful for prevention or treatment of hearing loss .

Accordingly, in another aspect, the present invention provides a method for preventing or treating hearing loss by administering a pharmaceutical composition comprising an onion skin extract or quercetin to an individual including a human in need thereof.

As used herein, the term "individual" means all animals, including humans, who have already developed or are at risk of having deafness. By administering the composition of the present invention to an individual, the disease can be effectively prevented and treated.

The composition of the present invention is administered in a pharmaceutically effective amount. As used herein, the term "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment for medical treatment and the effective dosage level will vary depending on the species and severity, The sex, the activity of the drug, the sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And can be administered singly or multiply. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without adverse effect, and can be easily determined by those skilled in the art.

The pharmaceutical composition of the present invention may contain a pharmaceutically acceptable carrier and may be administered orally or parenterally in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups or aerosols, And sterile injectable solutions.

Such pharmaceutically acceptable carriers may be those conventionally used in the art such as lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, But are not limited to, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In addition, the pharmaceutical composition of the present invention includes diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants, and other pharmaceutically acceptable additives.

When the pharmaceutical composition of the present invention is formulated into a solid preparation for oral use, it includes tablets, pills, powders, granules, capsules and the like. Such solid preparations contain at least one excipient such as starch, calcium carbonate, Sucrose or lactose, gelatin, and the like, including, but not limited to, lubricants such as magnesium stearate, talc, and the like.

When the pharmaceutical composition of the present invention is formulated orally for oral use, it includes suspensions, solutions, emulsions, syrups and the like, and includes, but is not limited to, diluents such as water and liquid paraffin, wetting agents, sweetening agents, .

When the pharmaceutical composition of the present invention is formulated for parenteral use, it may contain a sterilized aqueous solution, a non-aqueous solvent, a suspending agent, an emulsion, a lyophilized preparation and a suppository. Examples of the non-aqueous solvent include propylene glycol, polyethylene glycol, Vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like. Examples of suppositories include, but are not limited to, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The pharmaceutical composition of the present invention may be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically) depending on the intended method, and the dose may vary depending on the condition and the weight of the patient, The mode of administration, the route of administration, and the time, but may be appropriately selected by those skilled in the art.

The dose of the onion skin extract or quercetin contained in the pharmaceutical composition of the present invention varies depending on the condition and body weight of the patient, the age, the degree of disease, the drug form, the administration route and the period, but can be appropriately selected by those skilled in the art . For example, the onion skin extract may be administered at a dose of 1 to 2000 mg / kg, preferably 10 to 2000 mg / kg per day, with quercetin at 1 to 2000 mg / kg per day, 10 to 2000 mg / kg, and the administration may be administered once a day or divided into several times.

In another aspect, the present invention provides a health functional food for preventing or ameliorating hearing loss, preferably noise-induced hearing loss comprising onion skin extract or quercetin.

The onion, onion skin extract, quercetin and deafness are as described above.

The food composition of the present invention can be used as a health functional food. The term "health functional food" in the present invention means a food prepared and processed by using a raw material or ingredient having a useful function in the human body according to Law No. 6727 on health functional foods, and " It means that the structure and function of the human body is ingested for the purpose of obtaining nutritional effect or useful effect for health use such as physiological action.

The food composition of the present invention may contain conventional food additives, and the suitability of the above-mentioned "food additives" is not limited by the general provisions of the Food Additives Ordinance approved by the Food and Drug Administration, It shall be judged according to standards and standards for items.

Examples of the substances found in the above-mentioned "food additives" include natural compounds such as ketones, chemical compounds such as glycine, potassium citrate, nicotinic acid and cinnamic acid, coloring pigments, licorice extracts, crystalline cellulose, high- L-glutamic acid sodium preparations, noodle-added alkalis, preservative preparations, tar pigment preparations and the like.

The food composition of the present invention may contain 0.01 to 95% by weight, preferably 1 to 80% by weight of onion skin extract, preferably 0.01 to 80% by weight, based on the total weight of the composition, of quercetin for the purpose of preventing and / 95% by weight, preferably 1 to 80% by weight.

In addition, the food composition of the present invention can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, and circles for the purpose of preventing and / or improving the deafness.

For example, the health functional food in tablet form may be prepared by granulating a mixture of onion skin extract or quercetin, an excipient, a binder, a disintegrant, and other additives by a conventional method, The mixture can be directly compression molded. The health functional food of the tablet form may contain a mating agent and the like if necessary, and may be sieved to a suitable skin care agent if necessary.

The hard capsule of the capsule type health functional food can be prepared by filling a normal hard capsule with a mixture of an onion skin extract or an additive such as quercetin and an excipient or a granular product thereof or a gelatinized granule. Shell extract or a mixture of quercetin and an excipient such as an excipient into a capsule base such as gelatin. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a coloring agent, a preservative and the like, if necessary.

The ring-shaped health functional food can be prepared by molding an onion skin extract or a mixture of quercetin, excipient, binder, disintegrant and the like in an appropriate manner. If necessary, the skin may be coated with white sugar or other suitable skin care agent, It may also be an objectionable substance.

The granular health functional food may be prepared by granulating an onion skin extract or a mixture of quercetin, excipient, binder, disintegrant and the like by a suitable method, and if necessary, a flavoring agent, a mating agent and the like. In the granular form of health functional foods, when the next granularity test was carried out using the No. 12 (1680 μm), No. 14 (1410 μm) and No. 45 (350 μm) sieve, the total amount of the 12- 5.0% or less and that passing through the 45-well body may be 15.0% or less of the total amount.

The definitions of the above excipients, binders, disintegrants, lubricants, mating agents, flavoring agents, and the like are described in documents known in the art and include the same or similar functions (Korean Pharmacopoeia, College of Pharmacy, 5th ed., P. 33-48, 1989).

The onion skin extract or quercetin according to the present invention can effectively be used as a preventive, therapeutic and ameliorating agent for hearing loss by protecting the damage of hair cells due to noise and the like and effectively reducing the hearing threshold value measured by the auditory nerve.

FIG. 1 is a graph showing the results of measurement of the effect of the onion skin extract on the measurement of the jointing direction after noise exposure (control: untreated control, OPE: onion skin extract treatment group).
FIG. 2 is a graph showing the results of measurement of the effect of onion skin extract on hearing threshold measurement using a clearing-induced potential in a click stimulus sound after noise exposure (control: untreated control, OPE: onion skin extract treatment group).
FIG. 3 is a graph showing the results of measurement of the effect of onion skin extract on hearing threshold measurement using a clearing-induced potential in an 8 kHz TB stimulus after noise exposure (control: untreated control, OPE: onion skin extract treatment group).
FIG. 4 is a graph showing the results of measurement of the effect of onion skin extract on Na-Pa amplitude measurement using a medium-term reaction after noise exposure (control: untreated control, OPE: onion skin extract treatment group).
FIG. 5 is a graph showing the results of measuring the effect of quercetin on hearing threshold measurement using a quenching-induced potential in a click stimulus sound after noise exposure (control: untreated control group, Quercetin: quercetin treatment group).
FIG. 6 is a graph showing the results of measuring the effect of quercetin on hearing threshold measurement using a clearing-induced potential in a 4 kHz TB stimulus after noise exposure (control: untreated control group, quercetin: quercetin treatment group).
FIG. 7 is a graph showing the results of measuring the effect of quercetin in auditory threshold measurement using a cognitive evoked potential in an 8 kHz TB stimulus after noise exposure (control: untreated control group, Quercetin: quercetin treatment group).
FIG. 8 is a graph showing an improvement effect on the number of neuromastes damaged after neomycin treatment and fluorescence images (nor: neomycin untreated control group, con: onion skin extract untreated control group, OPE: onion skin Extract treatment group).
FIG. 9 is a graph showing an improvement effect on the number of damaged neuromastes after neomycin treatment and fluorescent images (nor: neomycin untreated control group, con: quercetin untreated control group, Quercetin: quercetin treated group) .

Hereinafter, the present invention will be described in more detail through examples and test examples. However, these examples and test examples are for illustrating the present invention, and the scope of the present invention is not limited to these examples and test examples.

[Example]

Example 1: Preparation of onion skin extract

500 g of onion skin was added to 10 L of 70% ethanol and extracted at 80 DEG C in an extraction vessel. This process was repeated three times, and the supernatant was collected. The supernatant was concentrated to 45 ° C using a vacuum condenser (EYELA, NN) and lyophilized at -40 ° C or lower for 12 hours or longer to obtain 30.04 g of onion skin extract ≪ / RTI >

[Experimental Example]

Experimental Example 1:

1. Mouse

Six-week-old ICR male mice were purchased from Young Bio (Seongnam, Korea). The mice were allowed free access to food and water, and were maintained in a humid environment, 12 hours a day at a constant temperature, and 12 hours a night cycle. After a week of adaptation to the kennel, auditory evoked potentials (AEPs) of the experimental animals were performed before the noise exposure to confirm normal hearing. The ABR threshold level of normal hearing mice was 25 dB.

2. Zebra fish

The wild-type Zebra fish (Danio rerio) was maintained in zebra fish system S type (1500 (W) ㅧ 400 (D) ㅧ 2050 (H) mm, Daejeon, Korea). Three pairs of zebrafish were placed in a scattering box overnight, and the next day the zebrafish began to spawn after a 30-60 minute light cycle. Three hours after fertilization, zebrafish eggs were collected and incubated in Petri dishes in 0.03% sea salt solution. The embryos were maintained in an incubator at 28 ° C with a cycle of 14 hours light and 10 hours darkness. The zebrafish used in the experiment was used on the 5th day after the modification.

Experimental Example 2. Confirmation of Protective Effect of Onion Peel Extract on Hair Cells after Noise Exposure - Otoacoustic Emission (OAE) Measurement Method

To evaluate the effect of onion skin extract on damage of hair cell cochlea in cochlea after exposure to noise,

The transient evoked otoacoustic emission (TEOAE) method is a method of measuring the sound emitted from the hair cells in the cochlea, and produces sound as a response to the sound stimulation in healthy hair cells. On the other hand, in injured hair cells, this reaction becomes smaller or disappears. To evaluate the effect of the onion skin extract on the noise - induced hearing loss, we performed a dorsal - phonocardiogram measurement because the cortical stimulus severely damaged the hair cells in the cochlea.

A mouse to which 100 mg / kg of onion skin extract prepared in Example 1 was administered and a control mouse to which nothing was administered (untreated control) were each divided into two groups of eight mice each. Noise was exposed to 120 dB broadband noise for 2 hours, and oral administration was given at the same time every day from 24 hours after noise exposure. On the 21st day after onion skin extract administration, Mice were anesthetized with ketamine (4.57 mg / kg) and silazane (0.43 mg / kg) and maintained at a temperature of 37 ± 0.5 ° C. The stimulus sound was measured at 90 dB and the test frequency was 6 kHz.

As a result, as shown in Fig. 1, the onion skin extract (OPE) group showed significantly higher OAE response than the control group, and the administration of onion skin extract (OPE) improved the damage of hair cell after noise exposure .

Experimental Example 3: Evaluation of hearing improvement effect of onion skin extract after noise exposure - Use of click sound

In the sense of the presence or absence of sound by measuring the hearing threshold after noise exposure In order to confirm the effect of onion skin extract, hearing threshold measurement experiment was carried out using the sensory evoked potential.

The auditory brainstem response (ABR) measurement is a method of evaluating the response to sound by measuring the electrical energy when a sound stimulus is transmitted to an electrical signal in the auditory nerve. When the sound reaches the auditory nerves through the outer ear, middle ear, and cochlea, it reflects all of the states of the ear, middle ear, and cochlea, reflecting the actual sound energy to which the sound energy reaches the brain. Hearing threshold refers to the minimum sensory point of sound that can be heard. In normal mice, the response is observed even on the average of 20 dB.

The mice to be administered with 100 mg / kg of the onion skin extract prepared in Example 1 and the untreated control mice were each divided into two groups of 8 mice each. The noise was exposed for 2 hours at 120 dB 4 KHz pure tone, and the onion skin extract was orally administered at the same time from 24 hours after exposure to noise. Hearing thresholds were evaluated on the 21st day of onion skin administration. Ketamine (4.57 mg / kg) and silazane (0.43 mg / kg) were anesthetized with an intramuscular injection and evaluated at a temperature of 37 ± 0.5 ° C. In the auditory evoked potential test, the stimulus sound was evaluated by lowering the sound gradually from 90 dB to 5 dB with a click of a broadband stimulus sound.

As can be seen in FIG. 2, the hearing threshold of the group treated with onion skin extract (OPE) was significantly lower than that of the control group. These results indicate that onion peel extract (OPE) is effective in the prevention and treatment of noise-induced hearing loss.

Experimental Example 4: Evaluation of hearing improvement effect of onion skin extract after noise exposure - Using 8 kHz TB stimulation sound

Hearing threshold was measured by 8 kHz stimulus sound after noise exposure, and hearing threshold measurement experiment was performed using clarification evoked potential to confirm hearing improvement effect of onion skin extract.

In the auditory evoked potential test, the stimulus sound was tested in the same manner as in Experimental Example 3 except that the sound was gradually decreased from 70 dB to 5 dB in 8 kHz TB. The results are shown in Fig.

As shown in Fig. 3, the hearing threshold of the group treated with onion skin extract (OPE) was lower than that of the control group. As with the results of the test using the click stimulant, the hearing threshold value of the group treated with the onion skin extract (OPE) was improved, and the onion skin extract (OPE) was effective in preventing and treating the hearing loss .

Experimental Example 5: Evaluation of hearing improvement effect of onion skin extract by mid-term response amplitude analysis after noise exposure

This study was conducted to compare the effects of onion skin extracts on noise-induced hearing loss by measuring the amplitude of Na-Pa in the mid-term results of electrophysiological evaluation after noise exposure.

The Auditory Middle Latency Response (AMLR) test is a reaction that occurs between 20 and 30 ms after the stimulation of the sound. The apex of the positive reaction is denoted as Pa, and the negative point before the reaction is denoted as Na. When there is hearing damage, the amplitude between Na-Pa tends to decrease. The mid-term response is a method of evaluating the central function of the auditory area near the midbrain of the auditory region.

The mice to be administered with 100 mg / kg of the onion skin extract prepared in Example 1 and the untreated control mice were each divided into two groups of 8 mice each. The noise was exposed for 2 hours at 120 dB 4 KHz pure tone, and the onion skin extract was orally administered at the same time every day from 24 hours after exposure to noise. The mid-term test was evaluated on the 21st day after administration of the onion skin extract. For the mid-term test, ketamine (4.57 mg / kg) and silazane (0.43 mg / kg) were anesthetized with an intramuscular injection in the mouse and maintained at a temperature of 37 ± 0.5 ° C. During the mid-term test, the stimulus was evaluated at 90 dB with a click.

As can be seen in FIG. 4, the control group was found to be damaged due to noise due to low amplitude after the noise exposure, and the group of the onion skin extract (OPE) group had significantly higher amplitude than the control group. The results of this experiment show that the onion skin extract (OPE) has an improvement effect on auditory central damage due to noise.

Experimental Example 6: Verification of hearing improvement effect of quercetin after noise exposure - Use of a click stimulus sound

The mice to be treated with quercetin 10 mg / kg and the untreated control mice were each divided into two groups of 8 mice each. Noise was exposed for 2 hours at 120 dB 4 KHz pure tone, and quercetin was administered orally at the same time every day from 24 hours after exposure to noise. Hearing thresholds were evaluated on the 21st day of onion skin administration. Ketamine (4.57 mg / kg) and silazane (0.43 mg / kg) were anesthetized with an intramuscular injection and evaluated at a temperature of 37 ± 0.5 ° C. In the auditory evoked potential test, the stimulus sound was evaluated by lowering the sound gradually from 90 dB to 5 dB with a click of a broadband stimulus sound.

As a result, as shown in FIG. 5, the hearing threshold of the quercetin-treated group was significantly lower than that of the control group. These results demonstrate that quercetin is effective in the prevention and treatment of noise-induced hearing loss.

Experimental Example 7: Verification of hearing improvement effect of quercetin after noise exposure - Using a 4 kHz TB (tone burst) stimulus sound

The hearing threshold was measured with a 4 kHz stimulus sound after noise exposure, and a hearing threshold measurement experiment was performed using the celestial evoked potential to confirm the hearing improvement effect of quercetin.

Experiments were performed in the same manner as in Experimental Example 6, except that the stimulus sound during the auditory evoked potential test was evaluated by lowering the sound gradually from 70 dB to 4 kHz TB (tone burst) by 5 dB. The results are shown in Fig.

As shown in Fig. 6, the hearing threshold of the quercetin-treated group was lower than that of the control group. As in the results of the test using the click stimuli, the hearing threshold value of the group administered with quercetin was improved, indicating that quercetin was effective in preventing and treating noise-induced hearing loss.

Experimental Example 8: Verification of hearing improvement effect of quercetin after noise exposure - Using 8 kHz TB (tone burst) stimulation sound

Hearing threshold was measured by 8 kHz stimulus sound after noise exposure, and the hearing threshold measurement experiment was performed using the celestial evoked potential to confirm the hearing improvement effect of quercetin.

Experiments were performed in the same manner as in Experimental Example 6, except that the stimulus sound during the cognitive evoked potential test was evaluated by lowering the sound gradually from 70 dB to 8 kHz TB (tone burst) by 5 dB. The results are shown in Fig.

As can be seen in FIG. 7, the hearing threshold of the quercetin-treated group was lower than that of the control group. As in the results of the test using the click stimuli, the hearing threshold value of the group administered with quercetin was improved, indicating that quercetin was effective in preventing and treating noise-induced hearing loss.

Experimental Example 9: Effect of onion skin extract and quercetin on neomycin-induced hair cell damage improvement

Wild-type zebrafish larvae were placed in 96-well plates and treated with 50 [mu] M neomycin sulfate for 1 hour. After rinsing with 0.03% sea salt solution, the zebrafish was exposed to onion skin extract 10 and 20 ug / mL, quercetin 5 and 10 μM for 12 hours at 28 ° C. After 12 hours of onion skin extract and quercetin treatment, zebrafish hair cells were exposed to 0.1% YO-PRO1 and stained for 30 minutes. Zebrafish larvae were anesthetized with 0.02% tricine and placed in 96-well plates. The number of hair cells in the neurons of the posterior fascia and the damage of the ear hair cells were observed by fluorescence microscopy. All images were analyzed with Focus Lite and Image J software.

As a result, as shown in Figs. 8 and 9, the onion skin extract (OPE) and quercetin significantly increased the number of neurons-damaged neurons in hair cells compared with the control (con) without onion skin extract or quercetin treatment .

Claims (6)

Onion skin ( Allium The present invention relates to a pharmaceutical composition for preventing or treating hearing loss, which comprises a cepa peel extract. The pharmaceutical composition according to claim 1, wherein the hearing loss is a noise-induced hearing loss. According to claim 1, wherein the onion extract is an onion skin of water, C ₁ ~C ₄ in an alcohol, and water and C ₁ ~C is manufactured by extraction with a solvent selected from the group consisting of a mixed solvent of alcohol and ₄ A pharmaceutical composition. Onion skin ( Allium The present invention relates to a food composition for preventing or ameliorating hearing loss. 5. The food composition of claim 4, wherein the hearing loss is a noise-induced hearing loss. The method of claim 4, wherein the onion extract is an onion skin of water, C ₁ ~C ₄ in an alcohol, and water and C ₁ ~C is manufactured by extraction with a solvent selected from the group consisting of a mixed solvent of alcohol and ₄ Food composition.

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