KR20130023880A - Composition for preventing or treating hearing loss comprising an extract of curculigo orchioides - Google Patents

Composition for preventing or treating hearing loss comprising an extract of curculigo orchioides Download PDF

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KR20130023880A
KR20130023880A KR1020110086956A KR20110086956A KR20130023880A KR 20130023880 A KR20130023880 A KR 20130023880A KR 1020110086956 A KR1020110086956 A KR 1020110086956A KR 20110086956 A KR20110086956 A KR 20110086956A KR 20130023880 A KR20130023880 A KR 20130023880A
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hearing loss
noise
extract
hearing
hair
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KR1020110086956A
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Korean (ko)
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강동호
홍빛나
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경희대학교 산학협력단
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/896Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH

Abstract

The present invention provides a pharmaceutical composition for the prevention or treatment of hearing loss comprising a hair extract. The present invention also provides a food composition for the prevention or improvement of hearing loss comprising a hair extract.
The composition according to the present invention can effectively suppress the increase in hearing thresholds due to noise and the like, thereby suppressing hearing loss, in particular acoustic trauma, transient or permanent noise-induced hearing loss. Therefore, the composition according to the present invention is effective for the prevention or treatment of hearing loss. In addition, oral administration is possible to increase patient compliance.

Description

Composition for preventing or treating hearing loss comprising an extract of Curculigo orchioides}

The present invention relates to a composition for preventing or treating hearing loss.

The ear is classified as the outer ear, the ear canal and the ear canal, and the eardrum and the osseous bone are classified as the middle ear, and the cochlea and auditory nerve as the inner ear. Sound is acoustic energy that is transmitted through the ear canal and ear canal to vibrate the eardrum. The vibrations of the tympanic membrane are mechanical energy that is transmitted to the osseous bone, which consists of three small bones attached to the eardrum. The spine, the last bone of the iso bone, is connected to the cochlea, which transfers energy to lymphatic fluid in the cochlea. The energy delivered causes waves in the lymph, which stimulate the hair cells in the cochlea. As the movement of the hair cells causes ion changes, neurotransmitters are delivered to the auditory nerves attached to the hair cells, and sound energy is transmitted from the auditory nerves to the brain in the form of electrical energy. The outer and middle ear are sound-carrying organs that can be recovered by treatment or surgery when they are infected with diseases such as inflammation, and their hearing loss can also be improved after treatment. This deafness is called conductive hearing loss. Hearing loss caused by problems in the cochlea, the organ that senses sound, the auditory nerve that delivers sound through electrical energy, and the brain that plays a comprehensive role, such as discrimination and understanding of sound, is called sensorineural hearing loss. do.

Among the sensory organs of the body, the auditory organ is one of the most important senses in language acquisition, knowledge acquisition, social life, and human life. Most hearing loss is sensory nerve deafness that has no treatment other than prevention until now. Once hearing loss occurs, it is helped by hearing aids such as hearing aids or by implanting mechanical devices into the body. Sensorineural hearing loss can be classified according to the cause and period of the onset, and depending on the time, it is classified as congenital hearing loss and acquired hearing loss. Congenital deafness was damaged before birth and can be caused by heredity, problems in the fetus, or problems in the birth process. Congenital deafness is most severe and even language acquisition is impossible without additional training and education. Most people with congenital hearing loss have a high-powered hearing aid or cochlear implant (a method of stimulating the auditory nerve with electrical stimulation to implant the device in their body and listen while wearing a separate external device). However, hearing aids and cochlear implants, such as hearing loss is more severe, the effect is less effective, and the difference between normal listening ability is still a lot of inconvenience in everyday life. In the case of acquired hearing loss, it is caused by disease, noise, drugs or accidents after birth, and there are noise, drugs, aging, trauma, and viruses. One of the most notable factors in recent years is hearing loss due to noise and aging. Advances in science and technology have prolonged the lifespan of humans and, accordingly, the elderly population is rapidly increasing worldwide. Geriatric hearing loss is also mostly sensorineural hearing loss, so there are no drugs or methods for treatment or improvement other than prevention and management. Recently, as the society industrialized, the hearing loss caused by noise has also increased rapidly. In addition to occupational noise-induced hearing loss such as workers and soldiers working in the noise environment, noise-induced hearing loss due to cultural and leisure life is increasing. According to Korea's Industrial Accident Law, exposure to environmental noise above 90 dBA can damage hearing. The Occupational Safety and Health Administration (OSHA) conducts noise management for noise environments above 85 dBA. Studies have shown that human hearing organs are affected by noise above 75 dBA. The noise of 75 dBA is that of cars along the road, so in the industrial society, everyone can live in a level of noise harmful to hearing organs. In addition to the environmental noise that is inevitably heard, adolescents are often exposed to loud sounds in their leisure life, including the use of MP3s. The noise-induced hearing loss caused by the use of MP3 in younger days impairs hearing enough to be able to communicate only when hearing aids are used in the 40's, and the degree of hearing loss becomes more severe when physical aging is combined. Aids such as hearing aids are also less effective as the degree of hearing loss worsens, so hearing loss of high severity will cause serious problems in communication. In other words, when the young generation experiencing the current noise-induced hearing loss becomes elderly, the degree of hearing loss becomes more severe, and deafness has an important influence in determining the quality of life of various generations from the old to the young.

Recently, as a research to find an effective substance for the prevention and treatment of hearing loss, preclinical studies on antioxidants, N-methyl-D-aspartate (NMDA) antagonists, apoptosis inhibitors, growth factors, etc. Has been reported, but there is a limit to progression to clinical trials (Prasher D., Lancet , 352 , pp 1240-1242, 1998). In the early stages of research, the use of antioxidants to neutralize reactive oxygen species (ROS) and reactive nitrogen species (RNS) inhibited cell damage in cochlea, but animal studies have not shown them. Did not. N-acetylcysteine (NAC) and methionine (methionine, MET) have been reported to be useful for the prevention of hearing loss, and NAC is a prodrug of GSH that enhances GSH production (Meister A., Pharmacol Ther ., 51 , pp 155-194, 1991). High-dose NAC is a mucopolysaccharide hydrolyzable enzyme for respiratory-related diseases, which has the effect of preventing noise-induced hearing loss, and MET is converted to cysteine as a pure amino acid. Other researchers have been interested in studying apoptosis and have reported that the GPx mimic function in relation to antioxidants plays a preventive role in noise-induced external hair cell damage. Among these studies, Mg, NAC and Ebselen have been shown to be effective until the clinical stage. A daily dose of 4 g of Mg granules in 300 young soldiers was reported to be less permanently impaired as compared to a placebo-effect control group after a week of noise exposure (Attias J. et al., Am . J.). Otolaryngol ., 15 , pp 26-32, 1994). For soldiers exposed to low-intensity noise, administration of Mg reduced transient hearing damage, indicating that permanent hearing damage was reduced in the 600 US Navy group administered NAC during two weeks of weapon training. In animal models, high doses of NAC have been shown to have a protective effect on noise-induced hearing loss, but have been reported to have limited hearing loss (Kopke RD et al., Hear . Res ., 149 , pp138-146, 2000; Kramer S. et al., American Academy of Audiology Annual Convention and Expo , Washington DC, USA , Poster Presentation , pp 502, 2005).

It has been reported that the use of Epsellen in 60 US soldiers during two weeks of weapon training has been shown to be effective for temporary and permanent hearing damage (Yamasoba T. et al., Neurosci . Lett ., 380 , pp234-238, 2005).

To date, no drugs have been approved for the prevention and treatment of noise-induced hearing loss. Only pre-clinical studies and clinical studies of Mg, NAC and espelen have been reported to the academic community.

On the other hand, Astragalus is a rhizome of Curculigo orchioides Gaertner belonging to the family Amarylidaceae. It contains liposide, lycoline, aliphatic hydroxyketones and mukorage, and it is known that methanol extract of hairy hair improves the phagocytosis of macrophages and is effective in glucoside fractionation. Pharmacology, Book Publishing Company, Ilil, February 2005, p.680).

An object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of hearing loss.

It is another object of the present invention to provide a food composition for preventing or improving hearing loss.

In order to achieve the above object, the present inventors have searched for a variety of active substances that can prevent or treat hearing loss in natural products with excellent safety, surprisingly found that the hair extract extract effectively suppresses the increase of hearing threshold due to noise. The present invention was completed.

Accordingly, the present invention provides a pharmaceutical composition for the prevention or treatment of hearing loss, including sun hair extract.

The present invention provides a food composition for the prevention or improvement of hearing loss comprising a hair extract.

The composition of the present invention may be applied to the prevention or treatment of hearing loss caused by various causes, in particular, noise-induced hearing loss.

Said hair extract is an extracting solvent selected from the group consisting of water, C 1 ~ C 4 alcohol, and a mixed solvent of water and C 1 ~ C 4 alcohol, preferably with an aqueous solution of ethanol, It can be obtained by performing an extraction process comprising.

Said hairs may be selected from one or more from the group consisting of paramunsam, dokkyak hairs, and seoksan.

The composition according to the present invention can effectively suppress the increase in hearing thresholds due to noise and the like, thereby suppressing hearing loss, in particular acoustic trauma, transient or permanent noise-induced hearing loss. Thus, the compositions according to the invention are useful for the prevention or treatment of hearing loss.

In addition, oral administration is possible to increase patient compliance.

Figure 1 shows the result of measuring the effect of the hair extract in the measurement of the noise after noise exposure (control: untreated control, COR300: experimental group treated with hair extract).
Figure 2 shows the result of measuring the effect of the hair extract in the hearing threshold measurement using the hearing oil development in the click stimulus sound after noise exposure (control: untreated control, COR300: experimental hair treatment group).
Figure 3 shows the result of measuring the effect of the hair extract in the hearing threshold measurement using the auditory oil generator in 3 kHz TB stimulation sound after noise exposure (control: untreated control, COR300: experimental group treated with hair extract).
Figure 4 shows the results of measuring the effect of the hair extract in the hearing threshold measurement using the hearing oil development level at 4 kHz TB stimulation sound after noise exposure (control: untreated control, COR300: experimental group treated with hair extract).
Figure 5 shows the result of measuring the effect of the hair extract in the hearing threshold measurement using the hearing oil development in the 6 kHz TB stimulation sound after noise exposure (control: untreated control, COR300: experimental treatment group).
Figure 6 shows the results of measuring the effect of the hair extract in the hearing threshold measurement using the auditory oil generator in 8 kHz TB stimulation sound after noise exposure (control: untreated control, COR300: experimental group treated with hair extract).
Figure 7 shows the result of measuring the effect of the hair extract in the Pa latency period measurement using the mid-term reaction after noise exposure (control: untreated control, COR300: experimental hair treatment group).
Figure 8 shows the results of measuring the effect of the hair extract in the Na-Pa amplitude measurement using the medium-term reaction after noise exposure (control: untreated control, COR300: experimental hair treatment group).

The term "hearing loss" as used herein includes both conductive hearing loss and sensorineural hearing loss. Preferably, it includes prenegative hearing loss caused by various causes such as noise, drugs, aging, trauma, viruses and the like. In particular, sensorineural hearing loss includes noise induced hearing loss (NIHL), which is a symptom of damage to the cochlea and auditory nerve by various noises. The noise deafness includes both acoustic trauma hearing loss, temporary threshold shift due to short time noise, and permanent threshold shift due to long time noise. .

The present invention provides a pharmaceutical composition for the prevention or treatment of deafness, including curculigo orchioides extract.

In the present invention, the hairline may be selected from one or more selected from the group consisting of paramunsam, dokkyak hairline, and seoksan.

The hair extract in the present invention is an extract comprising extracting with an extraction solvent (primary extraction solvent) selected from the group consisting of water, C 1 ~ C 4 alcohol, and a mixed solvent of water and C 1 ~ C 4 alcohol It can be obtained by carrying out the process. The primary extraction solvent is preferably an aqueous ethanol solution.

The extraction process may be carried out by extracting with the primary 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 hair. The mixed solvent may preferably use about 70% aqueous ethanol solution. Extraction may be performed by an extraction method known in the art, such as cold soaking, hot water extraction, ultrasonic extraction, reflux cooling extraction, but is not limited thereto. The extraction temperature may be employed by those skilled in the art in various temperature ranges suitable for the extraction method, for example, may be carried out at 20 ℃ to 100 ℃, etc., but is not limited thereto. In addition, the extraction time is different depending on the extraction method, a person skilled in the art can adopt an appropriate extraction time, but is not limited to this, can be performed in a single or multiple times in the range of about 1 hour to 10 days. Preferably, the extraction may be carried out by extraction with the above-mentioned primary extraction solvent 2 to 3 times at room temperature for about 2 days. Extract obtained by performing extraction with the primary extraction solvent is obtained in a liquid form by removing impurities by filtration in accordance with a conventional method, or concentrated liquid extract and concentrated in a reduced pressure and / or dried in accordance with a conventional method in the form of a powder You can get it.

In addition, the extraction process may further comprise the step of obtaining a fraction having a high content of the active ingredient, if necessary. For example, after dispersing the extract obtained by extraction with the primary extraction solvent in water, and then extracting with an appropriate secondary extraction solvent, such as alcohol of saturated C 4, the active ingredient content in the resulting extract Can be further increased.

The pharmaceutical composition of the present invention may comprise 0.01 to 95% by weight, preferably 1 to 80% by weight of the hairy extract relative to the total weight of the composition.

The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier, and oral dosage forms, external preparations, suppositories, and the like, powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc. according to conventional methods, respectively. It may be formulated in the form of sterile injectable solutions.

Such pharmaceutically acceptable carriers are those commonly used in the art, such as lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, Calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like. In addition, the pharmaceutical compositions of the present invention include diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, and other pharmaceutically acceptable additives.

When the pharmaceutical composition of the present invention is formulated as an oral solid preparation, it includes tablets, pills, powders, granules, capsules and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate, sucrose or rock. Toze, gelatin, and the like, and include but are not limited to lubricants such as magnesium stearate, talc, and the like.

When the pharmaceutical composition of the present invention is formulated for oral liquid preparation, it includes a suspending agent, a liquid solution, an emulsion, a syrup, and the like, and includes, but is not limited to, diluents such as water and liquid paraffin, wetting agents, sweeteners, fragrances, preservatives, and the like.

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

The dosage of the hair extract contained in the pharmaceutical composition of the present invention depends on the condition and weight of the patient, age, extent of disease, drug form, route of administration, and duration, and may be appropriately selected by those skilled in the art. For example, the hair extract may be administered at a dose of 1 to 2000 mg / kg, preferably 10 to 2000 mg / kg, and the administration may be administered once or several times a day.

The pharmaceutical composition of the present invention can be applied to mammals such as rats, mice, livestock, humans, etc. in various routes, for example orally, or intraperitoneally or intravenously, intramuscularly, subcutaneously, intrauterine dural or intracerebroventricular (Intracerebroventricular) injections. May be administered.

The pharmaceutical composition according to the present invention is effective for the prevention or treatment of deafness including all-neural hearing loss and sensory-neural hearing loss, in particular, acoustic traumatic hearing loss, temporary threshold increase due to short-term noise and permanent increase due to long-term noise. It is effective in preventing or treating noise-induced hearing loss.

The present invention also provides a food composition for the prevention or improvement of hearing loss, preferably noise-induced hearing loss, comprising a hair extract as an active substance.

Regarding sun hair extract which is an active ingredient contained in the food composition of the present invention, the above-mentioned content may be applied as it is.

The food composition of the present invention can be used as a dietary supplement. The term "health functional food" means a food manufactured and processed using raw materials or ingredients having functional properties useful for the human body according to Act No. 6767 of the Health Functional Food Act, and "functionality" refers to the structure of the human body. And ingestion for the purpose of obtaining nutrients for function or for obtaining useful effects in health uses such as physiological actions.

The food composition of the present invention may include a conventional food additives, and the suitability as the "food additives", unless otherwise specified, corresponding items according to the General Regulations and General Test Methods of the Food Additives approved by the Food and Drug Administration It is determined by the standard and the standard.

Examples of the items listed in the "Food Additive Revolution" include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamon acid, natural additives such as color pigments, licorice extracts, crystalline cellulose, high color pigments, guar gum, Mixed preparations, such as a sodium L- glutamate preparation, an addition of an alkali, a preservative preparation, and a tar pigment preparation, are mentioned.

The food composition of the present invention may contain 0.01 to 95% by weight, preferably 1 to 80% by weight of the hairy hair extract, based on the total weight of the composition, for the purpose of preventing and / or improving hearing loss, in particular, noise-induced hearing loss. The hair extract contained in the food composition of the present invention can be obtained by the same method as the extraction method mentioned in the preparation of the pharmaceutical composition.

The food composition of the present invention may be prepared and processed in the form of tablets, capsules, powders, granules, liquids, pills, beverages and the like for the purpose of preventing and / or improving hearing loss.

For example, the health functional food in the form of tablets may be granulated with conventional hair extracts, excipients, binders, disintegrants, and other additives in a conventional manner, and then compression-molded with a lubricant or the like. Direct compression can be performed. In addition, the health functional food in the form of tablets may contain a mating agent and the like, if necessary, may be coated with a suitable coating agent.

Hard capsules among the health functional foods in the form of capsules may be prepared by filling a conventional hard capsule with a mixture of an extract such as hairy hair extract, an excipient, and the like, or granular or peeled granules thereof. And a mixture with additives such as excipients in a capsule base such as gelatin. The soft capsule agent may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, as necessary.

Ring-shaped dietary supplements can be prepared by molding mixtures of sun hair extracts, excipients, binders, disintegrating agents, etc. in a suitable manner. You may be greeted.

The health functional food in the form of granules may be prepared by granulating a mixture of a hair extract, an excipient, a binder, a disintegrating agent and the like in an appropriate manner, and may contain a flavoring agent, a copper, and the like as necessary. For the health functional food in the form of granules, No. 12 (1680 μm), No. 14 (1410 μm) and No. 45 (350 μm) were used for the next particle size test. Less than 5.0% and passing through the 45 can be less than 15.0% of the total amount.

The term definitions of the excipients, binders, disintegrants, glidants, copulation agents, flavoring agents, etc. are described in the literature known in the art and include those having the same or similar functions (Korean Pharmacopoeia, Munseongsa, Korea Pharmacy University Council, 5th edition, p33-48, 1989).

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 sun hair extract

500 g of hairs were put in 10 L of 70% ethanol, and extracted at 80 ° C. in an extraction container. This process was repeated three times, and the supernatant was collected, concentrated at 45 ° C. under reduced pressure condenser (EYELA, NN), and then freeze-dried at -40 ° C. for 12 hours using an ILSHIN lyophilizer. Obtained.

[Test Example]

Test Example 1. Confirmation of hair cell protective effect of hair extract after noise exposure-Measurement of transient evoked otoacoustic emission (TEOAE)

To determine the effect of sun hair extract on hair cell (cochlea) damage in the cochlea after noise exposure, a two-acoustic radiation measurement experiment was performed.

Transient evoked otoacoustic emission (TEOAE) measurement is a method of measuring the sound generated from the hair cells in the cochlea from outside, and healthy hair cells generate sound in response to sound stimulation. In damaged hair cells, on the other hand, the response is reduced or disappeared. Since noisy stimulation severely damages hair cells in the cochlea, two-sided acoustic measurements were performed to confirm the effect of the hair extract on noise-induced hearing loss.

Mice to be administered 300 mg / kg of the hair extract prepared in Example 1 and control mice treated with nothing (untreated) were divided into two groups of 8 mice each. Noise was exposed for 2 hours with 120 dB wideband noise, and hair extract was fed 30 min before noise exposure and orally administered at the same time each day. Biacoustic emission measurements were assessed at 1, 5 and 7 days after noise exposure. Mice were anesthetized by administering ketamine (4.57 mg / kg) and silazine (0.43 mg / kg), and the stimulation sound was evaluated as 90 dB while maintaining body temperature of 37 ± 0.5 ° C.

As shown in FIG. 1, the TEAAE showed higher TOEAE response than the control group in the hairy extract (COR300) administration group, which showed a greater difference as the administration period increased. In the control group, TEOAE response intensity did not increase over time, indicating that the hair cells were damaged due to noise, whereas the hair line extract (COR300) group showed improvement in hair cells after noise exposure.

Test Example 2. Confirmation of hearing improvement effect of sun hair extract after noise exposure-Use of click stimulus sound

After hearing the noise, the hearing threshold was measured. In order to confirm the effect of the hair extract, a hearing threshold measurement experiment was performed using the QAS.

Auditory brainstem response (ABR) measurement is a method of evaluating the response to sound by measuring the electrical energy when the sound stimulus is transmitted as an electrical signal from the auditory nerve. When sound reaches the auditory nerve through the outer ear, middle ear, and cochlea, it reflects the state of the outer ear, middle ear, and cochlea, which reflects the actual sound energy that reaches the brain. Hearing threshold refers to the minimum sensory point of audible sound. On the average mouse, the response is observed even at a low sound level of 20 dB.

The parent hair extract prepared in Example 1 was evaluated by dividing into two groups of 8 mice each to be administered 300 mg / kg and untreated control mice. Noise was exposed for 2 hours with 120 dB 4 KHz pure sound, and hair extract was fed 30 minutes before noise exposure and orally administered at the same time every day. Hearing thresholds were assessed 1, 5 and 7 days after noise exposure. For the audit, the ketamine (4.57 mg / kg) and silazine (0.43 mg / kg) were anesthetized by intramuscular injection and then maintained at 37 ± 0.5 ° C. The stimulus sound was evaluated as a wide-band stimulus click sound, which was gradually lowered from 90 dB to 5 dB, and the threshold value was the smallest sound.

As shown in FIG. 2, the increased hearing threshold measured 24 hours after noise exposure was similar in both groups, and the control group showed similar thresholds for 7 days indicating permanent hearing impairment. Hearing threshold decreased significantly after 5 days of administration in the group treated with sun hair extract (COR300). These results confirm that sun hair extract (COR300) is effective in preventing and treating noise-induced hearing loss.

Test Example 3 Confirmation of the hearing improvement effect of sun hair extract after noise exposure-Use of 3 kHz TB stimulus

After the noise exposure, the hearing threshold was measured using a 3 kHz stimulus sound.

The test was conducted in the same manner as in Test Example 2, except that the stimulus sound was evaluated by gradually lowering the sound by 70 dB from 3 dB to a burst of 3 kHz tone. The results are shown in Fig.

As shown in FIG. 3, the control group had a hearing threshold of about 18 dB increased after exposure to noise, and showed a similar or rather increased hearing threshold increase for 7 days, indicating permanent hearing loss. In the group treated with sunscreen extract (COR300), the threshold was significantly decreased from the 5th day compared with the control group, and on the 7th day, the threshold was lowered to the same level as before the noise exposure. Similar to the results of the test using the click stimulus, the group treated with linear hair extract (COR300) showed a significant improvement in hearing threshold, indicating that the hairline extract (COR300) was effective in preventing and treating noise-induced hearing loss. Confirmed.

Test Example 4. Confirmation of the hearing improvement effect of sun hair extract after noise exposure-using 4 kHz TB stimulus

After the noise exposure, the hearing threshold was measured using a 4 kHz stimulus, and the hearing threshold measurement experiment was performed using the auditory oil generator to confirm the hearing improvement effect of the hair extract.

The test was conducted in the same manner as in Test Example 2, except that the stimulus sound was evaluated by gradually lowering the sound by 4 dB from 70 dB to 4 kHz TB as the noise exposure stimulus test. The results are shown in FIG.

As shown in FIG. 4, the control group had a 21 dB increase in hearing threshold measured after noise exposure, and showed a similar or rather increased hearing threshold increase over 7 days, indicating permanent hearing loss. In the group of sunscreen extract (COR300), the threshold was significantly decreased from the 5th day compared to the control group, and on the 7th day, the threshold was decreased by 10 dB compared to the control group, which showed a significant hearing improvement effect compared to the control group. Similar to the results of the test using the click stimulus and 3 kHz TB stimulus, the group treated with sun hair extract (COR300) showed a high improvement in hearing threshold, so the sun hair extract (COR300) was used for the prevention and treatment of noise It was confirmed to show the effect.

Test Example 5 Confirmation of the hearing improvement effect of sun hair extract after noise exposure-Use of 6 kHz TB stimulation sound

After the noise exposure, the hearing threshold was measured using a 6 kHz stimulus sound, and the hearing threshold measurement experiment was performed using the auditory oil generator to confirm the hearing improvement effect of the hair extract.

The test was conducted in the same manner as in Test Example 2, except that the stimulus sound was evaluated at 6 kHz TB, which is a frequency close to the noise exposure stimulus, and gradually decreased from 70 dB to 5 dB. The results are shown in Fig.

As can be seen in FIG. 5, the control group had a 30 dB increase in hearing threshold measured after noise exposure and showed a similar or rather increased hearing threshold increase over 7 days, resulting in permanent hearing loss. In the group treated with sunscreen extract (COR300), the threshold was significantly decreased from the 5th day compared to the control group, and on the 7th day, the threshold was decreased by 21 dB compared to the control group. Similar to the results of the test using the click stimulus and 3 and 4 kHz TB stimulus, the group treated with sun hair extract (COR300) had a significant improvement in hearing threshold. It has been shown to be effective in the treatment.

Test Example  6. Confirmation of the hearing improvement effect of sun hair extract after noise exposure-8 kHz TB Stimulation  use

After the noise exposure, the hearing threshold was measured using 8 kHz stimulus to determine the hearing improvement of the hair extract.

The test was carried out in the same manner as in Test Example 2 except that the stimulus sound was gradually lowered by 5 dB from 70 dB to 8 kHz TB.

The results are shown in FIG.

As shown in FIG. 6, the control group had a 34 dB increase in hearing threshold measured after noise exposure, and showed a permanent hearing loss due to a slight decrease or a similar increase in hearing threshold for 7 days. In the group treated with the parent extract (COR300), the threshold was significantly decreased from the 5th day compared to the control group, and on the 7th day, the threshold was decreased by 25 dB compared to the control group, and the hearing improvement effect was shown. Similar to the results of the test using the click stimulus and 3, 4 and 6 kHz TB stimulus, the group treated with the corticosteroid extract (COR300) showed a significant improvement in the hearing threshold. It has been shown to be effective in prevention and treatment.

Test Example 7 Confirmation of hearing improvement effect of sun hair extract through analysis of latent mid-term reaction after noise exposure

This study was conducted to determine the effectiveness of treatment of noise-induced deafness in the hair extract by measuring the absolute latency of Pa in the mid-term response test during electrophysiological evaluation after noise exposure.

The Auditor Middle Latency Response (AMLR) test is a response that occurs between 20 and 30 ms after sound stimulation. The vertex of the positive response is called Pa, and the negative point before the reaction is called Na. Hearing impairment tends to increase the latency of Pa response and decrease the amplitude between Na-Pa. The mid-term response is a method of assessing the central function of hearing as it is near the middle brain of the auditory area.

The parent hair extract prepared in Example 1 was evaluated by dividing into two groups of 8 mice each to be administered 300 mg / kg and untreated control mice. Noise was exposed for 2 hours with 120 dB 4 KHz pure sound, and hair extract was fed 30 minutes before noise exposure and orally administered at the same time every day. Mid-term tests were assessed on day 1, day 5, and day 7 after noise exposure. For the mid-term test, ketamine (4.57 mg / kg) and silazine (0.43 mg / kg) were anesthetized by intramuscular injection of mice, and evaluated at 37 ± 0.5 ° C. In the mid-term test, the stimulus sound was evaluated for Pa latency and Na-Pa amplitude at 90 dB by click.

As shown in FIG. 7, the control (control) was found that the latent period after the noise exposure is later than before the noise exposure, there is damage due to noise, and the group of administration of sunscreen extract (COR300) appeared shorter than the control group. On day 5, the incubation period of the sunscreen extract (COR300) group was similar to that of the normal group, which improved the incubation period due to hearing impairment. The incubation period reflects the time the electrical energy is transferred to the auditory nerve. The incubation period is extended when hearing loss or hearing nerve damage occurs. This test result shows that the hair loss extract (COR300) has a therapeutic effect on noise-induced hearing loss when the change of incubation period is observed for 7 days after noise exposure.

Experimental Example 8. Confirmation of hearing improvement effect of sun hair extract through analysis of medium-term reaction amplitude after noise exposure

This study was conducted to compare the effect of treatment of noise-induced deafness on sunscreen by measuring the amplitude of Na-Pa in the mid-term response test during electrophysiological evaluation after noise exposure.

The test was carried out in the same manner as in Test Example 7, except that the amplitude of Na-Pa was analyzed during the audit mid-reaction test. The results are shown in FIG.

As shown in Figure 8, the control (control) was confirmed that there is damage due to noise by lowering the amplitude after noise exposure, the hairline extract (COR300) administration group showed a lower amplitude reduction than the control and maintained for 7 days thereafter It was. This test result shows that the hair extract (COR300) has a therapeutic effect on noise-induced hearing loss when the amplitude change is observed for 7 days after noise exposure.

As described above, sun hair extract is useful for the prevention and treatment of hearing loss by protecting hair cells from damage caused by deafness such as noise-induced hearing loss and reducing hearing threshold measured by the hearing nerve. Thus, the hair extract may be used for the prevention and treatment of sensorineural hearing loss.

[Example]

The following formulation was prepared using the hair extract obtained in Example 1. However, the following formulation examples are merely illustrative of the present invention, whereby the content of the present invention is not limited.

Formulation Example 1 Preparation of Tablet

Sun Hair Extract ............... 200 mg

Lactose ......................................... 100 mg

Starch ........................................ 100 mg

Magnesium Stearate ...............

Tablets were prepared by mixing and tableting the above components according to a conventional tablet production method.

Formulation example  2. Liquid  Produce

Sesame extract .................................... 1000 mg

CMC-Na ........................................................... .20 g

Heterosaccharides ......................................................... 20 g

Lemon scent ... Quantity

Purified water was added to adjust the total volume to 1000 ml. According to the conventional method for preparing a liquid, the above components were mixed, and then filled into a brown bottle and sterilized to prepare a liquid.

Formulation Example 3. Preparation of capsules

Sun hair extract ......................................... 300 mg

Crystalline Cellulose ......................................... 3 mg

Lactose ............... 14.8 mg

Magnesium Stearate ......... 0.2 mg

According to a conventional capsule preparation method, the above ingredients were mixed and filled into gelatin capsules to prepare capsules.

Formulation Example 4. Preparation of injection

Sun Hair Extract ......................................... 300 mg

Mannitol ......................................... 180 mg

Sterile Distilled Water for Injection ............... 2974 mg

Na 2 HPO 4 12H 2 O ........................................ 26 mg

According to the conventional method for preparing an injection, the amount of the above ingredient was prepared per ampoule (2 ml).

Claims (8)

A pharmaceutical composition for the prevention or treatment of hearing loss, comprising an extract of Curculigo orchioides . The pharmaceutical composition of claim 1, wherein the hearing loss is noise-induced hearing loss. The method of claim 1 wherein glandulour hairs extract extraction comprises extraction with an extraction solvent selected from the group consisting of a glandulour hairs with water, C 1 ~ C 4 alcohol, and water and mixed solvent of a C 1 ~ C 4 alcohol Pharmaceutical compositions obtained by carrying out the process. The pharmaceutical composition according to any one of claims 1 to 3, wherein the hairline is at least one member selected from the group consisting of paramunsam, dokkyak hair, and oxane. Food composition for the prevention or improvement of hearing loss containing sun hair extract. 6. The food composition of claim 5, wherein the hearing loss is noise-induced hearing loss. 6. The method of claim 5, glandulour hairs extract extraction comprises extraction with an extraction solvent selected from the group consisting of a glandulour hairs with water, C 1 ~ C 4 alcohol, and water and mixed solvent of a C 1 ~ C 4 alcohol A food composition obtained by carrying out the process. The food composition according to any one of claims 5 to 7, wherein the hairline is at least one member selected from the group consisting of paramunsam, dokkyak hairpin, and oxan.
KR1020110086956A 2011-08-30 2011-08-30 Composition for preventing or treating hearing loss comprising an extract of curculigo orchioides KR20130023880A (en)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101432939B1 (en) * 2013-06-05 2014-08-22 대구한의대학교산학협력단 Pharmaceutical composition having extract of curculigo orchioides for prevention or treatment of reflux esophagitis
WO2019004775A3 (en) * 2017-06-29 2019-02-28 동국제약 주식회사 Pharmaceutical composition for preventing or treating hearing loss comprising avocado oil as active ingredient
KR20190073112A (en) * 2017-12-18 2019-06-26 경희대학교 산학협력단 Composition for preventing or treating hearing loss comprising Viscum ovalifolium extracts
KR102028383B1 (en) * 2018-11-12 2019-10-04 (주)운트바이오 Composition for preventing or treating hearing loss
KR102030123B1 (en) * 2018-05-31 2019-10-08 경희대학교 산학협력단 Composition for preventing or treating hearing loss

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101432939B1 (en) * 2013-06-05 2014-08-22 대구한의대학교산학협력단 Pharmaceutical composition having extract of curculigo orchioides for prevention or treatment of reflux esophagitis
WO2019004775A3 (en) * 2017-06-29 2019-02-28 동국제약 주식회사 Pharmaceutical composition for preventing or treating hearing loss comprising avocado oil as active ingredient
KR20190073112A (en) * 2017-12-18 2019-06-26 경희대학교 산학협력단 Composition for preventing or treating hearing loss comprising Viscum ovalifolium extracts
KR102030123B1 (en) * 2018-05-31 2019-10-08 경희대학교 산학협력단 Composition for preventing or treating hearing loss
KR102028383B1 (en) * 2018-11-12 2019-10-04 (주)운트바이오 Composition for preventing or treating hearing loss

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