KR20190073099A - Composition for preventing or treating hearing loss comprising Uncaria rhynchophylla extracts - Google Patents

Abstract

The present invention provides a composition for preventing, alleviating or treating hearing loss containing an extract of Uncaria rhynchophylla. The composition according to the present invention effectively inhibits the increase of a hearing threshold and hair cell damage due to hearing loss, thereby being able to inhibit hearing loss. Therefore, the composition is useful for preventing or treating hearing loss, thereby being able to be usefully used as a pharmaceutical composition or a health functional food.

Description

(Composition for preventing or treating hearing loss comprising Uncaria rhynchophylla extracts as an active ingredient)

The present invention relates to the use of < RTI ID = 0.0 > Uncaria & rhynchophylla ) extracts. The present invention also relates to a composition for preventing or treating hearing loss.

The research and development of diseases related to the ear was mostly related to diseases caused by inflammation such as bacterial otitis externa, malignant otitis, bacterial otitis externa, fungal infection, otitis media or otitis externa, and the technical development of related therapies was mainly performed .

Specifically, the disease (external ear infection) is inflammation of the external ear and external ear canal. Acute otitis is a common cause of ear infection in humans, and inflammation can be caused by bacterial, viral or bacterial organisms. The outer ear canal often swells, is painful, and it can hurt when touched. Otitis media (middle ear infection) occurs in the area between the inner ears, including the eardrum and the eustatic tube. Otitis media is very common in children, with an average of 2-3 children per year, usually with viral upper respiratory infection (URI), and most cases with cold. Rhinoviruses and adenoviruses, which cause very common cold symptoms, cause swelling and redness in the inner ear. Otitis media is also common with a variety of bacteria and other viruses.

Most of the above-mentioned ear-related diseases were treated with antibiotics, anti-inflammatory drugs and the like. Up to now, most therapeutic agents are based on antibiotics or anti-inflammatory drugs.

However, in the modern society, problems related to hearing loss due to cell or nerve damage are more serious than the above-mentioned inflammation-based ear related diseases due to increase of noise exposure and aging of the population. In addition, the general public can distinguish between ear related diseases caused by inflammation such as bacterial otitis externa, malignant otitis, bacterial otitis externa, fungus otitis, otitis media, and hearing loss caused by cellular or nerve injury, Hearing loss is one of the most prevalent diseases in the modern society. In addition to the causes of noise and aging, such as hearing loss caused by these cells or nerve damage, these toxic drugs, nervous system toxic chemicals, viral, genetic, etc., are sometimes unknown.

For the treatment of gastrointestinal disorders, many specialists and practitioners involved in the pharmaceutical industry are still seeking treatment of gastric diseases as a therapeutic agent based on conventional antibiotics or antiinflammatory agents, but this can not be used as a suitable therapeutic agent for deafness. The reason for this is that there are no known treatments for hearing loss, and secondly, many experts and practitioners in the medical industry do not clearly recognize the treatment for hearing loss. These problems cause the problem that the hearing loss can not be properly treated.

In particular, the use of antibiotics represents a major problem with this toxicity. For example, aminoglycoside antibiotics have side effects of toxicity and renal toxicity that cause hearing and equilibrium dysfunction in the inner ear, as well as overdosage, as well as long-term dosing with therapeutic doses, In some cases. Aminoglycoside antibiotics This toxicity occurs in both ears in the form of acute severe hearing loss, with vestibular dysfunction in approximately 15% of users and hearing loss in 10-30%, mainly at high frequencies above 4000 Hz.

Thus, although preclinical studies on various drugs have been reported as research for finding effective substances for the prevention and treatment of hearing loss, it has been confirmed that there is a limit to progress to clinical trials. In addition, to date, no drugs have been approved for the prevention and treatment of hearing loss. Furthermore, there is hardly any developed drug for hearing loss therapeutic agents using natural or natural materials that can be used without toxicity or risk to human body. In other words, unlike the ear related diseases caused by inflammation, no therapeutic agent suitable for deafness has been developed at all.

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 food or medicine material is urgently required.

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

The present invention relates to the use of < RTI ID = 0.0 > Uncaria & rhynchophylla ) as an active ingredient. The present invention also provides a pharmaceutical composition for prevention or treatment of deafness.

The present invention also provides a food composition for preventing or ameliorating hearing loss comprising an extract of Uncaria rhynchophylla .

The present inventors have aimed at the prevention of hearing loss, a natural plant material with excellent stability, improved and amenities to find substances that can cure sought results, surprisingly unka Ria rincho Pilar (Uncaria rhynchophylla ) extract effectively prevented, ameliorated, and treated the hearing loss, and completed the present invention.

The present invention relates to the use of < RTI ID = 0.0 > Uncaria & rhynchophylla ) as an active ingredient. The present invention also provides a pharmaceutical composition for prevention or treatment of deafness.

The pharmaceutical composition for preventing or treating hearing loss of the present invention has an effect of effectively increasing the hearing threshold value due to hearing loss and effectively inhibiting hair cell damage, and thus has an excellent therapeutic effect on hearing loss.

In the present invention, the term " hearing loss " means any condition in which the hearing loss or loss occurs.

The hearing loss includes both conductive hearing loss and sensorineural hearing loss. Herein, the former voice hearing loss is a hearing loss caused by an ear disease, which is caused by a problem in an organ such as a tympanic membrane and an ossicle, which is an organ that transmits sound. Sensory nerve impairment is a hearing loss caused by problems in the brain responsible for hearing, which plays a comprehensive role, such as the cochlea, which is the organ that senses sound, the auditory nerve that transmits sound by electric energy, and the discrimination and understanding of sound. The cause of sensory nerve impairment may be hearing loss caused by noise, drugs, aging, trauma, etc., and may be, for example, this toxic hearing loss. The toxic hearing loss is caused by the toxic drugs gentamicin, streptomycin, kanamycin, neomycin, amikacin, tobramycin, administration of one or more drugs selected from the group consisting of neilmicin, dibekacin, sisomycin, livodomycin, cisplatin, carboplatin and oxaliplatin. Lt; / RTI >

Preferably, the hearing loss may include noise-induced hearing loss, senile hearing loss, sudden hearing loss, auditory neuropathy caused by diabetes, poisonous hearing loss, traumatic hearing loss and viral hearing loss. However, The present invention is not limited to the category of hearing loss.

Uncaria rhynchophylla ) is a plant belonging to the family Rubiaceae. It is mainly a plant in Southeast Asia, such as Vietnam, Philippines and China. The above-mentioned Uncaria rhynchophylla ) can be extracted without being restricted to plant parts such as flowers, outposts, leaves, stems, seeds, fruits and roots.

The above-mentioned Uncaria rhynchophylla ) extracts were prepared according to the conventional method for preparing extracts from Uncaria rhynchophylla ). For example, Uncaria < RTI ID = 0.0 > preferably from about 1 to 20 times, preferably from about 3 to about 10 times, the weight of the rhynchophylla , preferably water, C ₁ to C ₄ lower alcohols (such as methanol, ethanol, propanol, isopropanol, Butanol, etc.) or a mixed solvent thereof. Extraction can be carried out by methods known in the art such as, for example, cold-pressing, hot water extraction, ultrasonic extraction, reflux-cooling extraction, and the like. The extraction temperature can be varied by a person skilled in the art in a variety of temperature ranges suitable for the extraction method, for example, but not limited to, from 20 캜 to 100 캜. Further, the extraction time differs depending on the extraction method, and a person skilled in the art can adopt an appropriate extraction time, but can be performed in a single or multiple cycles in a range of about 1 hour to 10 days, although not limited thereto. The extract obtained by performing the extraction with the primary extraction solvent may be obtained in the form of a liquid in which impurities are removed by filtration according to a conventional method, or the obtained liquid form extract may be concentrated under reduced pressure and / Can be obtained.

The extraction step may further include, if necessary, obtaining a fraction having a high active ingredient content. That is, the step of dispersing the extract obtained by extracting with the primary extraction solvent into water and then extracting with an appropriate secondary extraction solvent, for example, an alcohol of water saturated C ₁ -C ₄ is carried out to increase the content of the active ingredient .

According to one embodiment of the present invention, Uncaria < RTI ID = 0.0 > rhynchophylla (Miq.) Miq. ex Havil was extracted with methanol to prepare an aqueous solution of Uncaria rhynchophylla methanol aqueous solution. Specifically, Uncaria < RTI ID = 0.0 > rhynchophylla ) were extracted from 80% (v / v) methanol extract at 80 ℃ for 1 hour.

The inventive Uncaria < RTI ID = 0.0 > rhynchophylla ) extract as an active ingredient, but it is not limited thereto. The extract of Uncaria rhynchophylla may be contained in an amount of 0.1 to 95% by weight based on the total weight of the composition.

The pharmaceutical composition of the present invention may contain a pharmaceutically acceptable carrier and may be in the form of powders, granules, tablets, capsules, suspensions, emulsions, oral preparations such as syrups and aerosols, external preparations, Can be formulated in the form of sterile injectable solutions.

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

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

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

When the pharmaceutical composition of the present invention is formulated for parenteral use, it may contain a sterilized aqueous solution, a non-aqueous solvent, a suspending agent, an emulsion, a lyophilized preparation and a suppository. Examples of the non-aqueous solvent include propylene glycol, polyethylene glycol, Vegetable oils such as 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.

The dosage of Uncaria rhynchophylla extract contained in the pharmaceutical composition of the present invention varies depending on the condition and body weight of the patient, age, degree of disease, drug form, route of administration, and period of time, . For example, Uncaria < RTI ID = 0.0 > rhynchophylla ) extract may be administered at a dose of 0.0001 to 100 mg / kg per day, preferably 0.001 to 10 mg / kg per day, and the administration may be administered once a day or divided into several times.

The pharmaceutical composition of the present invention may be administered to mammals such as rats, mice, livestock, humans, and the like by various routes, for example, oral, intraperitoneal or intravenous, muscular, subcutaneous, intrauterine, .

The present invention also relates to the use of < RTI ID = 0.0 > Uncaria & rhynchophylla ) extract as an active ingredient.

The food composition of the present invention can be used as a health functional food. The term "functional food" as used herein means a food produced or processed by using raw materials or ingredients having functionality useful to the human body according to the Act on Health Functional Foods, and "functional" refers to the structure and functions of the human body Means taking nutrients for the purpose of obtaining a beneficial effect for health use such as controlling nutrients or physiological action.

The food composition of the present invention may contain conventional food additives, and the suitability of the term "food additives" as referred to above is to be determined by the Food and Drug Administration according to the General Rules and General Test Methods approved by the Food and Drug Administration It shall be judged according to standards and standards for items.

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

The food composition of the present invention may contain 0.01 to 95% by weight, preferably 1 to 80% by weight of Uncaria rhynchophylla extract, based on the total weight of the composition. The extract of Uncaria rhynchophylla contained in the food composition of the present invention can be obtained in the same manner as the extraction method mentioned in the production of the above pharmaceutical composition.

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

For example, the health functional food in the form of tablets may be prepared by granulating a mixture of Uncaria rhynchophylla extract, excipient, binder, disintegrant, and other additives in a conventional manner, and then adding a lubricant or the like Compression molding, or direct compression molding of the mixture. The health functional food of the tablet form may contain a mating agent and the like if necessary, and may be sieved to a suitable skin care agent if necessary.

The hard capsules of the health functional foods in the form of capsules are prepared by mixing Uncaria rhynchophylla extract, or an excipient, or a mixture thereof, or a granular material or a granular material, and the soft capsule may be prepared by mixing Uncaria rhynchophylla ) extract and an excipient, into a capsule base such as gelatin. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a coloring agent, a preservative and the like, if necessary.

The health functional food of the ring form is Uncaria ( Uncaria) rhynchophylla ) extract, excipient, binder, disintegrant and the like may be formulated by a suitable method. If necessary, the mixture may be converted into white sugar or other suitable skin care agent, or starch, talc or a suitable substance.

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

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

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

The present invention relates to the use of < RTI ID = 0.0 > Uncaria & rhynchophylla ) extract of the present invention to a subject.

The term " Uncaria " rhynchophylla ) extract "," hearing loss "and" administration "are the same as those described above.

The subject refers to an animal, and typically can be a mammal that may have beneficial effects in treatment with the Uncaria rhynchophylla extract of the present invention. A preferred example of such a subject may include primates such as humans. Such subjects may also include all subjects with or at risk of having symptoms of hearing loss.

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

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

The present invention also provides the use of the above Uncaria rhynchophylla extract for the treatment of hearing loss.

In accordance with the present invention, the < RTI ID = 0.0 > Uncaria & rhynchophylla ) extract effectively inhibits the increase of hearing threshold due to hearing loss and hair cell damage, thereby being useful for prevention or treatment of hearing loss and thus useful as a pharmaceutical composition or a health functional food.

Fig. 1 is a schematic diagram of the Uncaria < RTI ID = 0.0 > rhynchophylla ) treated with neomycin to treat the hair cells damaged by neomycin treatment to confirm the prevention, treatment and improvement effects thereof (NOR: neomycin untreated normal control, NM: neomycin induced untreated control, URE: Uncaria rhynchophylla ) 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. Uncaria Lincho pillar  ( Uncaria rhynchophylla ) Preparation of extract

Uncaria of origin of Vietnam rhynchophylla (Miq.) Miq. The ex Havil 80% (v / v) methanol extract was distributed at the Korea Biotechnology Center, Korea.

Above Uncaria rhynchophylla (Miq.) Miq. The ex Havil 80% (v / v) methanol extract was obtained from the above-mentioned Uncaria Linzipila (Miq.) Miq. ex Havil. ( Uncaria rhynchophylla (Miq.) Miq. ex Havil.) was extracted with 80% (v / v) methanol at 80 ℃ for 1 hour. This procedure was repeated once to prepare an extract. The extract was concentrated at a temperature of 55 캜 by a vacuum concentrator, and then lyophilized to obtain Uncaria rhynchophylla ) was finally prepared.

Example 2 In this toxic zebrafish model, uncaria rinchopila ( Uncaria rhynchophylla ) Effect of Extract on Hair Cell Protection

Example 1 Uncaria < RTI ID = 0.0 > rhynchophylla ) extracts were treated with neomycin - reduced hair cells and their hairy cell protective effect was confirmed.

Specifically, 6 day post fertilization zebrafish larvae were placed in 24 wells and exposed to 2 μM neomycin for 1 hour. Thereafter, the supernatant of Uncaria < RTI ID = 0.0 > rhynchophylla ) extract at 1 μg / mL for 6 h, and treated with 0.03% sea salt solution as a control. Fluorescence microscopy (Olympus 1 × 70, Olympus, Japan) was used for direct hair cell observation and stained with 0.1% YO-PRO for 30 min. Zebrafish fish were anesthetized with 0.02% tricine and the hair cells were observed under a fluorescence microscope. The data were analyzed by counting the number of hair cells obtained through fluorescence microscopy.

The results are shown in Fig.

As can be seen in Figure 1, Uncaria < RTI ID = 0.0 > rhynchophylla ) treated group, the number of hair follicle cells was significantly increased. Thus, it was confirmed that the number of hair follicle cells of Uncaria according to the present invention rhynchophylla ) extracts showed excellent effects in the prevention, improvement and treatment of hearing loss.

[Formulation Example]

The uncaria of Uncaria < RTI ID = 0.0 > rhynchophylla ), the following formulation was prepared. However, the following formulation examples are illustrative of the present invention, and the contents of the present invention are not limited thereto.

Preparation Example 1. Preparation of tablets

Uncaria rhynchophylla ) Extract ......... 1000 mg

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

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

Magnesium stearate ........................................ Amount

The above components were mixed and tableted according to a conventional tablet preparation method to prepare tablets.

Formulation Example 2. Preparation of a liquid preparation

Uncaria rhynchophylla ) Extract ......... 1000 mg

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

Isolation Party ................................................ .... 20 g

Lemon flavor ................................................ ......

Purified water was added to adjust the total volume to 1000 ml. The above components were mixed according to a conventional method for producing a liquid agent, and then filled in a brown bottle and sterilized to prepare a liquid agent.

Formulation Example 3. Preparation of capsules

Uncaria rhynchophylla ) 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

Uncaria rhynchophylla ) Extract ......... 1000 mg

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

Sterile sterilized distilled water for injection ....................................... 2974 mg

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

(2 ml) per ampoule according to the usual injection preparation method.

Formulation Example 5. Preparation of Health Functional Drink

Uncaria rhynchophylla ) extract ............. 100 mg

Citric acid ................................................. ..... 1000 mg

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

Plum concentrate ................................................ ..... 2 g

Add purified water to the whole ........................................ 900 mL

The health functional beverage was prepared by mixing the above components according to a conventional health functional drink manufacturing method.

Claims (10)

Uncaria rhynchophylla ) as an active ingredient. The pharmaceutical composition according to claim 1, wherein the hearing loss is a conductive hearing loss or a sensorineural hearing loss. The method according to claim 1, wherein the hearing loss is one or more selected from the group consisting of noise-induced hearing loss, senile hearing loss, sudden hearing loss, auditory neuropathy due to diabetes, toxic hearing loss, traumatic hearing loss and viral hearing loss A pharmaceutical composition. The method according to claim 1, wherein said Uncaria rhynchophylla ) extract is an extract of water, a lower alcohol of C ₁ to C ₄ or a mixed solvent thereof. 5. The method according to claim 4, wherein said Uncaria rhynchophylla ) extract was obtained from Uncaria rhynchophylla ) aqueous solution of methanol, which is a pharmaceutical composition for preventing or treating hearing loss. Uncaria rhynchophylla ) as an active ingredient. The food composition according to claim 6, wherein the hearing loss is a conductive hearing loss or a sensorineural hearing loss. The method according to claim 6, wherein the hearing loss is one or more selected from the group consisting of noise-induced hearing loss, senile hearing loss, sudden hearing loss, auditory neuropathy caused by diabetes, toxic hearing loss, traumatic hearing loss and viral hearing loss Food composition. 7. The method according to claim 6, wherein said Uncaria < RTI ID = 0.0 > rhynchophylla ) extract is an extract of water, a lower alcohol of C ₁ to C ₄ or a mixed solvent thereof. 10. The method according to claim 9, wherein said Uncaria < RTI ID = 0.0 > rhynchophylla ) extract was obtained from Uncaria rhynchophylla ) aqueous solution of methanol.

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