KR102075694B1 - Composition for preventing or treating hearing loss comprising Syzygium cumini extracts - Google Patents

Abstract

The present invention provides a composition for the prevention, improvement or treatment of deafness, including Syzygium cumini extract.
The composition according to the present invention can suppress hearing loss by effectively suppressing the increase of hearing threshold and hair cell damage due to hearing loss, and thus useful for the prevention or treatment of hearing loss, and can be useful as a pharmaceutical composition or health functional food.

Description

Composition for preventing or treating hearing loss containing Sygigum mini extract as an active ingredient {Composition for preventing or treating hearing loss Syzygium cumini extracts}

The present invention relates to a composition for the prevention or treatment of hearing loss, comprising Syzygium cumini extract.

The research and development of diseases related to the ear were mostly for diseases caused by inflammation such as bacterial otitis media, malignant otitis, fungal otitis, binary fungal infection, otitis media, or otitis media, and the development of technologies related to the treatments were mainly made. .

Looking specifically at the disease, otitis externa (external ear infection) is inflammation of the outer ear and ear canal. Otitis is a common cause of earaches in humans, and inflammation may be caused by a fungal, viral or bacterial organism. The external auditory meatus is often swollen, painful, and painful if touched. Otitis media (middle ear infection) occurs at the site between the tympanic membrane and the inner ear, which contains the eustachian tube. Otitis media is very common in children, on average infants experience 2-3 times a year, usually accompanied by viral upper respiratory tract infection (URI), and mostly colds. Rhinoviruses and adenoviruses, the most common cause of cold symptoms, cause swelling and hyperemia in the inner ear. Otitis media is also commonly caused by various bacteria and other viruses.

Most of the treatment of the ear-related diseases, such as those using antibiotics, anti-inflammatory drugs, etc., and to date, most of the therapeutic drugs are based on antibiotics or anti-inflammatory drugs.

However, due to the increase in noise exposure and the aging of the population, the problems related to hearing loss due to cellular or nerve damage are emerging, rather than the above-described inflammatory-based ear-related diseases. Moreover, most people can distinguish ear-related diseases caused by inflammation such as bacterial otitis, malignant otitis, fungal otitis, binary fungal infection, otitis media, or otitis and hearing loss caused by cellular or nerve damage. Hearing loss is one of the most prevalent and widely known diseases in modern society. Hearing loss caused by damage to cells or nerves may be caused by noise, aging, etc., as well as by toxic drugs, toxic chemicals in the nervous system, viral diseases, and genetics.

For the treatment of gastric deafness, a number of specialists and workers in the pharmaceutical industry are still aiming to treat the above diseases with antimicrobial or anti-inflammatory drugs based on existing antibiotics, but they cannot be used as a suitable treatment for hearing loss. The use of such a conventional treatment is because, firstly, there are no known treatments related to hearing loss, and secondly, a large number of specialists and medicine industry workers are not clearly aware of the treatment for hearing loss. Due to these problems, the problem of inadequately performing treatment for hearing loss continues to arise.

In particular, the use of antibiotics presents a major problem due to its toxicity. For example, aminoglycoside antibiotics have the side effects of toxic and nephrotoxicity that cause hearing and equilibrium dysfunction in the inner ear, which can occur not only in overdose but also in long-term doses as therapeutic doses, and in some cases even in short-term titration doses. This may occur. Aminoglycoside antibiotic toxicity is seen in both ears, with vestibular dysfunction in about 15% of users and hearing loss in 10-30%, mainly in the form of acute high hearing loss at high frequencies above 4000Hz.

Accordingly, preclinical studies on various drugs have been reported as studies to find an effective substance for the prevention and treatment of hearing loss, but it has been confirmed that there is a limit to proceeding to clinical trials. In addition, there are no approved drugs to date for the prevention and treatment of hearing loss. Moreover, few drugs have been developed for the treatment of deafness using natural materials or natural materials that can be used without toxicity or danger to the human body. In other words, unlike ear-related diseases caused by inflammation, no suitable treatment for hearing loss has been developed.

Under these circumstances, the research and development of a composition for preventing or treating hearing loss using a material that can be easily used as a material of food or drugs is urgently needed.

Korean Patent Application No. 10-1367479 Korean Patent Application No. 10-1777157

The present invention is Sijigum Cumini ( Syzygium cumini ) Provides a pharmaceutical composition for the prevention or treatment of hearing loss comprising the extract as an active ingredient.

In addition, the present invention is Sijigum Cumini ( Syzygium cumini ) provides a food composition for preventing or improving hearing loss comprising the extract.

The present inventors have made diligent efforts to find substances that can prevent, improve and treat hearing loss in natural plant materials with excellent safety. Surprisingly, Syzygium cumini extract effectively prevents, improves and treats hearing loss. It confirmed and completed this invention.

The present invention is Sijigum Cumini ( Syzygium cumini ) Provides a pharmaceutical composition for the prevention or treatment of hearing loss comprising the extract as an active ingredient.

The pharmaceutical composition for preventing or treating hearing loss of the present invention has an excellent therapeutic effect on hearing loss by having an effect of effectively suppressing the increase of hearing threshold and hair cell damage caused by hearing loss.

In the present invention, "hearing loss" means any state in which hearing is degraded or lost.

Hearing loss includes conductive hearing loss and sensorineural hearing loss. The pre-negative hearing loss is a hearing loss caused by the ear disease, the hearing loss caused by problems in the organs, such as the eardrum and bone bones that are organs that transmit sound. Sensorineural hearing loss is a 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, which plays a comprehensive role in the discrimination and understanding of sound. The cause of sensorineural hearing loss may be deafness caused by noise, drugs, aging, trauma, etc., for example, it may be toxic hearing loss. The toxic hearing loss is a toxic drug gentamicin (gentamicin), streptomycin (streptomycin), kanamycin (kanamycin), neomycin (neomycin), amikacin (amikacin), tobramycin, netylmycin ( Administration of any one or more drugs selected from the group consisting of netilmicin, dibekacin, sibeomycin, sisomycin, ribodomycin, cisplatin, carboplatin and oxaliplatin May be due to hearing loss.

In addition, the deafness may include noise deafness, senile deafness, sudden deafness, toxic deafness, traumatic deafness, viral deafness, and the like, but if the hearing is deteriorated or lost in the scope of the present invention deafness It is not limited and may be included in the disease range.

Clear Message Queue Mini (Syzygium cumini ), commonly known as zambolan , Java plum, black plum, etc., is a plant belonging to the family Myrtaceae. Mainly, it is a plant which lives in Southeast Asia, such as Vietnam, Philippines, and India. The extraction site of the Syzygium cumini may be extracted without being limited to plant parts such as flowers, outposts, leaves, stems, seeds, fruits and roots.

Sijigum Cumini ( Syzygium) cumini ) extract is Syzygium according to the conventional extract preparation method cumini ) can be extracted and prepared. For example, about 1 to 20 times, preferably about 3 to 10 times, the primary extractant, preferably water, C ₁ to C ₄ lower alcohols based on the weight of Syzygium cumini ( For example, methanol, ethanol, propanol, isopropanol, butanol and the like) or a mixed solvent thereof may be used for extraction. Extraction may be performed by an extraction method known in the art, such as cold soaking, hot water extraction, ultrasonic extraction, reflux cooling extraction, and the like, 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 ℃ and the like, 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, it can be performed in a single or multiple times in the range of about 1 hour to 10 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 a powder form 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. That is, the extract obtained by extracting with the primary extraction solvent is dispersed in water, followed by extraction with an appropriate secondary extraction solvent, for example, saturated C ₁ -C ₄ alcohol to enhance the content of the active ingredient. Can be.

According to one embodiment of the invention, Syzygium of Vietnamese origin cumini (L.) Syzygium by Extracting Skeels with Methanol cumini ) Methanol aqueous solution extract was prepared. Specifically, the outpost of Syzygium cumini was prepared by extracting at 80 ° C. for 1 hour in an 80% (v / v) methanol extract.

Syzygium of the present invention cumini ) It is preferable to include the Syzygium cumini ( Sizygium cumini ) extract in an amount of 0.1 to 95% by weight based on the total weight of the composition containing the extract as an active ingredient, but is not limited thereto.

The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier, and oral formulations, external preparations, suppositories, such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., respectively, according to conventional methods. 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 lactose, 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 sterile aqueous solution, non-aqueous solvent, suspending agent, emulsion, lyophilized preparation, suppository, and the non-aqueous solvent, suspending agent is propylene glycol, polyethylene glycol, olive Vegetable oils such as oils, injectable esters such as ethyloleate, and the like. Bases of suppositories may include, but are not limited to, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

Syzygium contained in the pharmaceutical composition of the present invention The dosage of cumini ) extract depends on the patient's condition and weight, age, extent of disease, drug form, route of administration and duration, but may be appropriately selected by those skilled in the art. For example, Syzygium cumini extract may be administered at a dose of 0.0001 to 100 mg / kg, preferably 0.001 to 10 mg / kg, and the administration may be divided once or several times a day. It may also be administered.

The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, etc. by various routes, for example, by oral, intraperitoneal or intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injections. .

The present invention is also referred to as Syzygium cumini ) includes a food composition for the prevention or improvement of hearing loss comprising the extract as an active ingredient.

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 the law on health functional foods, and "functionality" refers to the structure and function of the human body. It means the ingestion for the purpose of obtaining a useful effect for health use such as nutrient control or physiological action.

The food composition of the present invention may include a conventional food additive, and the suitability as the "food additive" is applicable according to the General Regulations and General Test Method of the Food Additives approved by the Ministry of Food and Drug Safety unless otherwise specified. It is judged by the standard and the standard about the item.

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 dark blue, licorice extract, crystalline cellulose, high pigment, guar gum, Mixed preparations, such as a sodium L- glutamate preparation, an alkali addition additive, a preservative preparation, and a tar pigment preparation, are mentioned.

The food composition of the present invention may comprise 0.01 to 95% by weight of Syzygium cumini extract, preferably 1 to 80% by weight, based on the total weight of the composition. Syzygium cumini 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.

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

For example, the dietary supplement in the form of tablets is a mixture of Syzygium cumini extract, excipients, binders, disintegrants, and other additives in a conventional manner, and then added with a lubricant, etc. Compression molding or the mixture may be compression molding directly. 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.

Capsules of hard capsules of the dietary food queue mini (Syzygium Clear message to a conventional hard capsules cumini ) extract, and a mixture with additives such as excipients or granules or granulated products thereof may be filled, and soft capsules are mixed with additives such as Syzygium cumini extract and excipients. It can be prepared by filling in a capsule base such as gelatin. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, as necessary.

The dietary supplement in cyclic form is Syzygium cumini ) Mixtures of extracts, excipients, binders, disintegrants, etc. may be prepared by molding in a suitable manner, and may be coated with sucrose or other suitable coating agent, or may be starved with starch, talc or a suitable substance.

The health functional food in the form of granules is Syzygium cumini ) Mixtures of extracts, excipients, binders, disintegrants and the like can be prepared into granules in a suitable manner, and may contain flavoring agents, copulating agents 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 body 45 may be less than 15.0% of the total amount.

The term definitions of the excipients, binders, disintegrants, glidants, copulation agents, flavoring agents and the like 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, pp. 33-48, 1989).

There is no particular limitation on the kind of food. Examples of foods to which the extract of the present invention may be added include beverages, gums, vitamin complexes, drinks, and the like, and include all health functional foods in a conventional sense.

The present invention is Sijigum Cumini ( Syzygium cumini ) provides a method for the treatment of hearing loss, comprising administering an extract to a subject.

In the present invention, "sijigum cumini ( Syzygium) cumini ) extract "," hearing loss "and" administration "and the like are the same as described above.

The subject refers to an animal, and may be a mammal, which may typically have a beneficial effect with treatment with Syzygium cumini extract of the present invention. Preferred examples of such subjects may include primates, such as humans. In addition, such subjects may include all subjects having symptoms of or at risk of having such symptoms.

The present invention also provides the use of said Syzygium cumini extract in the manufacture of a medicament for the treatment of hearing loss.

The present invention also provides a composition comprising said Syzygium cumini extract for use in the treatment of hearing loss.

The present invention also provides the use of said Syzygium cumini extract for the treatment of hearing loss.

Sijigum cumini ( Syzygium) according to the present invention cumini ) extract can suppress hearing loss by effectively suppressing hearing loss and hair cell damage caused by hearing loss, which can be useful for the prevention or treatment of hearing loss, and can be useful as a pharmaceutical composition or health food.

FIG. 1 shows the results of treatment of syzygium cumini extract on hair cells damaged by neomycin treatment to confirm its prevention, treatment and improvement (NOR: neomycin untreated normal control, NM: neomycin induction). Untreated control, SCE: Syzygium cumini extract 1 μg / mL treated group).

Hereinafter, the present invention will be described in more detail with reference to 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  One. Sijium Cumini  ( Syzygium cumini ) Preparation of Extract

Syzygium of Vietnamese origin cumini (L.) Skeels 80% (v / v) Methanol extract was distributed at the Korea Institute of Bioscience and Biotechnology, Overseas Biomaterials Center.

Stomach Syzygium cumini (L.) Skeels 80% (v / v) Methanol extracts are used for the cizium cumin (L.) Skeels ( Syzygium cumini (L.) Skeels) were extracted from 80% (v / v) methanol at 80 ° C for 1 hour. This process was repeated once to prepare an extract, and then concentrated in a vacuum condenser at 55 ℃ temperature, and then lyophilized to obtain a methanol extract of Syzygium cumini (final).

Example  2. Toxicity Zebrafish  In the model Sijium Cumini  ( Syzygium cumini Effect of Extracts on Hair Cells

Example 1 Syzygium cumini ) extract was treated with hair cells reduced by neomycin to confirm its hair cell protective effect.

Specifically, zebrafish larvae 6 days post fertilization (6 day post fertilization) were placed in 24 wells for 1 hour exposure to 2 μM neomycin. Thereafter, it was exposed for 6 hours by replacing 1 μg / mL of Syzygium cumini extract of Example 1, and treated with 0.03% sea salt solution as a control. Fluorescence microscopy (Olympus 1 × 70, Olympus, Japan) was used for direct observation of hair cells, and stained with 0.1% YO-PRO for 30 minutes. Zebrafish cheers were anesthetized with 0.02% tricaine and hair cells were observed by fluorescence microscopy. The data was analyzed by counting the number of hair cells obtained through a fluorescence microscope.

The results are shown in FIG.

As confirmed in FIG. 1, Syzygium cimini cumini ) It was confirmed that the number of hair cells significantly increased in the experimental group treated with extract, through which the Syzygium cumini extract according to the present invention has an excellent effect on the prevention, improvement and treatment of hearing loss. Confirmed.

[ Formulation example ]

Syzygium of Example 1 cumini ) to prepare the following formulation using the extract. 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 Tablets

Clear Message Queue Mini (Syzygium cumini ) extract .................. 1000 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

Clear Message Queue Mini (Syzygium cumini ) extract .................. 1000 mg

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

Isomerized sugar ... .... 20 g

Lemon flavor ...... suitable

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 Capsule

Clear Message Queue Mini (Syzygium cumini ) extract .................. 1000 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 Injectables

Clear Message Queue Mini (Syzygium cumini ) extract .................. 1000 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).

Formulation example  5. Preparation of Health Functional Beverages

Clear Message Queue Mini (Syzygium cumini ) Extract ..................... 100 mg

Citric Acid ... ..... 1000 mg

oligosaccharide ................................................. ... 100 g

Plum Concentrate ... ..... 2 g

Purified water is added to the total ..................... 900 mL

According to the conventional method for preparing a health functional beverage, the above components were mixed to prepare a health functional beverage.

Claims (10)

Syzygium cumini A pharmaceutical composition for the prevention or treatment of hearing loss comprising methanol extract as an active ingredient. The pharmaceutical composition for preventing or treating hearing loss according to claim 1, wherein the hearing loss is conductive hearing loss or sensorineural hearing loss. The pharmaceutical composition for preventing or treating hearing loss according to claim 1, wherein the hearing loss is any one selected from the group consisting of noise-induced hearing loss, senile hearing loss, sudden hearing loss, toxic hearing loss, traumatic hearing loss, and viral hearing loss. delete delete Syzygium cumini A food composition for preventing or improving hearing loss comprising methanol extract as an active ingredient. The food composition for preventing or improving hearing loss of claim 6, wherein the hearing loss is conductive hearing loss or sensorineural hearing loss. The food composition for preventing or improving hearing loss of claim 6, wherein the hearing loss is any one selected from the group consisting of noise-induced hearing loss, senile hearing loss, sudden hearing loss, toxic hearing loss, traumatic hearing loss, and viral hearing loss. delete delete

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