KR102007096B1 - Composition for preventing or treating hearing loss comprising Viscum ovalifolium extracts - Google Patents

Abstract

Biscum Obaliforium ( Viscum ovalifolium ) provides a composition for the prevention, improvement or treatment of hearing loss.
The composition according to the present invention can suppress hearing loss by effectively suppressing the increase of hearing threshold due to the hearing loss and hair cell damage, 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, comprising Viscum ovaliporium extract as an active ingredient {Composition for preventing or treating hearing loss comprising Viscum ovalifolium extracts}

Biscum Obaliforium ( Viscum ovalifolium ) relates to a composition for the prevention or treatment of hearing loss.

The research and development of diseases related to the ear has been 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 has been mainly performed. .

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 ear pain 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 eardrum and the inner ear, which contains the eustachian tube. Otitis media is very common in children, on average infants experience 2-3 times each 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 that use 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, to the extent that the general population can distinguish between ear-related diseases caused by inflammation such as bacterial otitis, malignant otitis, fungal otitis, binary fungus, 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 and nerves may include noise, aging, and other toxic drugs, neurotoxic chemicals, viruses, 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 the above-mentioned conventional treatments 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 the treatment of 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, there are few drugs developed for the treatment of hearing loss using natural materials or natural materials which 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, 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 pharmaceuticals is urgently needed.

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

Biscum Obaliforium ( Viscum ovalifolium ) 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 a biscum obaliporium ( Viscum ovalifolium ) Provides a food composition for the prevention or improvement of hearing loss.

As a result of our diligent efforts to find substances capable of preventing, improving and treating hearing loss in natural plant materials having excellent safety, the inventors surprisingly have a biscum obaliporium. ( Viscum ovalifolium ) extract was confirmed that effectively prevent, improve and treat hearing loss and completed the present invention.

Biscum Obaliforium ( Viscum ovalifolium ) 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 due to 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, a hearing loss caused by problems in the organs such as the eardrum and iso bone, which 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 such as 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 deafness is gentamicin (gentamicin), streptomycin (streptomycin), kanamycin (kanamycin), neomycin (neomycin), amykacin (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 hearing loss may include noise-induced hearing loss, senile hearing loss, sudden hearing loss, diabetic neuropathy, toxic hearing loss, traumatic hearing loss, viral hearing loss, and the like. It is not limited to the scope of hearing loss above, but may be included in the scope of the disease.

Viscum Obaliforium ( Viscum ovalifolium ) is a plant in the Viscaceae family. Mainly, it is a plant inhabiting Southeast Asia, such as Vietnam, Philippines, Malaysia. The Biscum Ovaliorium ( Viscum ovalifolium ) can be extracted without being restricted to plant parts such as flowers, outposts, leaves, stems, seeds, fruits, roots.

The Biscum Ovaliorium ( Viscum ovalifolium ) extract is biscum obaliporium according to the conventional extract preparation method ( Viscum ovalifolium ) can be prepared. For example, Viscum Obaliforium ( Viscum ovalifolium ) about 1 to 20 times, preferably about 3 to 10 times the primary extraction solvent, preferably water, C ₁ to C ₄ lower alcohols (eg methanol, ethanol, propanol, isopropanol, Butanol and the like) or a mixed solvent thereof. 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. 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 the obtained liquid form of the extract in a powder form by concentrating under reduced pressure and / or drying according to a conventional method 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, Viscum of Vietnamese origin ovalifolium Biscum Obaliforium Extracted with Methanol from DC. ( Viscum ovalifolium ) Methanol aqueous solution extract was prepared. Specifically, Viscum Obaliforium ( Viscum ovalifolium ) outpost was prepared by extracting at 80 ° C. for 1 hour in 80% (v / v) methanol extract.

Biscum Obaliforium of the Invention ( Viscum bislifolium ) biscum obaliforium at 0.1 to 95% by weight relative to the total weight of the composition containing the extract as an active ingredient ( Viscum ovalifolium ) It is preferably included, but not limited to.

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 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 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 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, sweeteners, fragrances and preservatives.

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. Examples of suppositories include, but are not limited to, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

Biscum obaliporium contained in the pharmaceutical composition of the present invention The dosage of Viscum ovalifolium extract depends on the patient's condition and weight, age, extent of disease, drug form, route of administration and duration, and may be appropriately selected by those skilled in the art. For example, Viscum Obaliforium ( Viscum ovalifolium ) 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 administered once or several times a day.

The pharmaceutical compositions 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 a biscum obaliporium ( Viscum ovalifolium ) includes a food composition for the prevention or improvement of hearing loss containing 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 Law of the Food Additives approved by the Ministry of Food and Drug Safety unless otherwise specified. Judge according to the standards and standards for 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 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.

Food composition of the present invention is based on the total weight of the composition ( Viscum ovalifolium ) extract may comprise 0.01 to 95% by weight, preferably 1 to 80% by weight. Biscum obaliporium contained in the food composition of the present invention ( Viscum ovalifolium ) extract 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 is biscum obaliporium (Viscum ovalif o lium) may extract, excipient, binder, disintegrating agent and a granulating a mixture of the other additives in the usual way, and then, the lubricant to put the like compression molding or direct compression molding the mixture. 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 dietary supplements in the form of capsules are biscum obaliporium in conventional hard capsules (Viscum ovalif o lium) extract, and can be prepared by filling a mixture or a particulate material or a particulate of the skin and water with additives such as excipients, soft capsules are bis glutamicum misfire lipoic Solarium ( Viscum ovalifolium ) extract and a mixture with additives such as excipients can be prepared by filling the 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.

Biscum Obaliforium ( Viscum ovalifolium ) extracts, excipients, binders, disintegrants and the like can be prepared by molding in a suitable manner, and may be coated with sucrose or other suitable coating agent, or may be favored with starch, talc or a suitable substance.

Granular health food is biscum obaliporium ( Viscum ovalifolium ) extracts, excipients, binders, disintegrants, and the like mixture can be prepared in a granular manner, and may contain a flavoring agent, a coagulant 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).

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.

Biscum Obaliforium ( Viscum ovalifolium ) provides a method of treating deafness comprising administering to the subject.

In the present invention "Biscum Obaliforium ( Viscum ovalifolium ) extract "," hearing loss "and" administration "and the like are the same as described above.

The subject refers to an animal, and typically the biscum obaliporium of the present invention ( Viscum ovalifolium ) may be a mammal that can have a beneficial effect by treatment with an extract. 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 invention also relates to the biscum obaliporium in the manufacture of a medicament for the treatment of hearing loss ( Viscum ovalifolium ) provides the use of extracts.

The present invention is also the biscum obaliporium for use in the treatment of hearing loss It provides a composition comprising the extract ( Viscum ovalifolium ).

The present invention is also the biscum obaliporium for the treatment of hearing loss ( Viscum ovalifolium ) provides the use of extracts.

Biscum Obaliporium according to the present invention ( Viscum ovalifolium ) extract can inhibit hearing loss by effectively suppressing the increase of hearing threshold and hair cell damage caused by hearing loss, and thus can be useful for the prevention or treatment of hearing loss, and as a pharmaceutical composition or health functional food.

1 is a biscum obaliporium ( Viscum ovalifolium ) extracts were treated to the damaged hair cells by neomycin treatment to confirm their prevention, treatment and improvement (NOR: neomycin untreated normal control, NM: neomycin induced untreated control, VOE: biscum oval Liporium ( Viscum ovalifolium ) extract 1 μg / mL treatment 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 1.Biscum Obaliforium ( Viscum ovalifolium ) Preparation of extract

Viscum ovalifolium DC of Vietnamese origin. The 80% (v / v) methanol extract was distributed at the Korea Institute of Bioscience and Biotechnology, Overseas Biomaterials Center.

Gastric Viscum ovalifolium DC. 80% (v / v) methanol extract was obtained from the biscum obaliforium DC. The outpost of Viscum ovalifolium DC. Was extracted in 80% (v / v) methanol at 80 ° C for 1 hour. This process was repeated once to prepare an extract, concentrated in a vacuum condenser at 55 ° C., and then lyophilized to form biscum obaliforium. Methanol extract of Viscum ovalifolium was finally prepared.

Example 2 Biscum Obaliforium in a Toxicity Zebrafish Model ( Viscum ovalifolium Effect of Extracts on Hair Cells

Example 1 Viscum Obaliforium ( Viscum ovalifolium ) extracts were treated with the hair cells reduced by neomycin to confirm their hair cell protective effect.

Specifically, zebrafish larvae 6 days post fertilization (6 days post fertilization) were placed in 24 wells and exposed to 2 μM neomycin for 1 hour. Afterwards, the Viscum Obaliforium of Example 1 ( Viscum ovalifolium ) extract was replaced with 1 μg / mL for 6 hours, and 0.03% sea salt solution was treated 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, the Viscum Ovaliorium ( Viscum ovalifolium ) extract was treated in the experimental group was confirmed that the number of hair cells significantly increased, through which the biscum obaliporium according to the present invention ( Viscum ovalifolium ) extract was found to have an excellent effect on the prevention, improvement and treatment of hearing loss.

[Example]

Biscum Obaliforium of Example 1 ( Viscum ovalifolium ) extract was used to prepare the following formulation. 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

Viscum Obaliforium ( Viscum ovalifolium ) 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 Preparation of Liquid

Viscum Obaliforium ( Viscum ovalifolium ) 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 capsules

Viscum Obaliforium ( Viscum ovalifolium ) Extract .............. 1000 mg

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

Lactose ... 14.8 mg

Magnesium Stearate ... 0.2 mg

The above components were mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

Formulation Example 4. Preparation of injection

Viscum Obaliforium ( Viscum ovalifolium ) 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 Drink

Viscum Obaliforium ( Viscum ovalifolium ) 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 functional ingredients were mixed to prepare a health functional beverage.

Claims (10)

Pharmaceutical composition for the prevention or treatment of toxic hearing loss by neomycin (neomycin) comprising an extract of Viscum ovalifolium as an active ingredient. delete delete The pharmaceutical composition of claim 1, wherein the biscum obaliforium extract is an extract of water, a lower alcohol of C1 to C4, or a mixed solvent thereof. The pharmaceutical composition of claim 4, wherein the biscum obaliforium extract is an aqueous biscum obaliforium methanol extract. Food composition for the prevention or improvement of detoxifying hearing loss by neomycin comprising biscum obaliporium extract as an active ingredient. delete delete The food composition of claim 6, wherein the biscum obaliforium extract is an extract of water, C1 to C4 lower alcohol, or a mixed solvent thereof. The food composition of claim 9, wherein the biscum obaliforium extract is an aqueous biscum obaliforium methanol extract.

Images