KR20220091177A - Composition for preventing or treating hearing loss - Google Patents
Composition for preventing or treating hearing loss Download PDFInfo
- Publication number
- KR20220091177A KR20220091177A KR1020200182449A KR20200182449A KR20220091177A KR 20220091177 A KR20220091177 A KR 20220091177A KR 1020200182449 A KR1020200182449 A KR 1020200182449A KR 20200182449 A KR20200182449 A KR 20200182449A KR 20220091177 A KR20220091177 A KR 20220091177A
- Authority
- KR
- South Korea
- Prior art keywords
- hearing loss
- deafness
- methoxyphenylpropane
- dihydroxy
- diol
- Prior art date
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Abstract
본 발명은 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올을 유효성분으로 포함하는 난청의 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing or treating hearing loss comprising 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol as an active ingredient.
Description
본 발명은 난청의 예방 또는 치료용 조성물에 관한 것으로, 보다 바람직하게는 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올을 유효성분으로 포함하는 난청의 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing or treating hearing loss, more preferably for preventing or treating hearing loss comprising 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol as an active ingredient to the composition.
현재까지 귀와 연관된 질환들에 대한 연구 개발은 세균성 외이염, 악성 이염, 균성 외이염, 이진균증, 중이염, 또는 내이염와 같은 염증에 의해 유발되는 질환들에 대한 것이 대다수였으며, 이와 관련된 치료제들의 개발을 위주로 이루어지고 있다.Until now, most research and development on ear-related diseases have been on diseases caused by inflammation, such as bacterial otitis externa, malignant otitis, fungal otitis externa, otomycosis, otitis media, or otitis media. have.
귀와 연관된 질환을 구체적으로 살펴보면, 먼저, 외이염(외부 귀 감염)은 바깥 귀 및 외이도에서 발생하는 염증에 의한 것으로, 인간에서 귀앓이의 통상적인 원인이다. 상기 염증은 균성, 바이러스성 또는 세균성 유기체가 원인일 수 있다. 외이도 피부가 흔히 부풀어 오르고, 고통스러우며, 만지면 아플 수 있다. 다른 예로, 중이염(중간 귀 감염)은 고막과 유스타티오관을 포함하는 안쪽 귀 사이 부위에서 일어난다. 이는 어린이에게서 매우 흔하게 발병하는데, 평균적으로 유아는 매년 2 내지 3차례 경험하며, 통상 바이러스성 상기도 감염(URI) 및 대부분 감기와 수반된다. 중이염은 매우 흔한 감기 증상의 원인이 되는 리노바이러스(rhinoviruses) 및 아데노바이러스가 안쪽 귀안에 팽창과 충혈을 일으킬 수 있으며, 이외에도 다양한 세균 및 기타 바이러스에 의해 흔히 일어날 수 있다.Looking specifically at diseases related to the ear, first, otitis externa (external ear infection) is caused by inflammation occurring in the outer ear and the ear canal, and is a common cause of earache in humans. The inflammation may be due to a bacterial, viral or bacterial organism. The skin of the ear canal is often swollen, painful, and painful to the touch. In another example, otitis media (middle ear infection) occurs in the area between the eardrum and the inner ear, which includes the Eustatio tube. It is very common in children, and, on average, infants experience two to three times per year, usually accompanied by viral upper respiratory tract infections (URIs) and mostly colds. Otitis media can be caused by rhinoviruses and adenoviruses, which are the cause of very common cold symptoms, which can cause swelling and redness in the inner ear, and can also be caused by various bacteria and other viruses.
이와 같은 귀와 관련된 질환의 대부분은 염증을 수반하므로 그 치료는 약제로써 항생제, 항염증제 등을 이용하는 것들이었고, 현재까지도 대부분 치료제는 항생제 또는 항염증제를 기반으로 한다.Since most of these ear-related diseases accompany inflammation, the treatment has been to use antibiotics, anti-inflammatory agents, etc. as pharmaceuticals, and most treatments are still based on antibiotics or anti-inflammatory agents.
그러나, 현대 사회에서는 소음 노출의 증가 및 인구의 고령화 등으로 인하여 위와 같은 염증 기반의 귀 관련 질환보다는, 세포나 신경 손상에 의한 난청과 관련된 문제가 크게 대두되고 있다. 더욱이, 일반인들도 대부분 세균성 외이염, 악성 이염, 균성 외이염, 이진균증, 중이염, 또는 내이염 등의 염증이 원인이 되는 귀 관련 질환과 세포나 신경 손상에 의한 난청의 질환 차이를 구별할 수 있을 정도로, 난청은 현대 사회에 발병률이 높고 널리 알려진 질환 중 하나이다. 이러한 세포나 신경 손상에 의한 난청은 소음이나 노화 등의 원인 외에 이독성 약물, 신경계 독성 화학물질, 바이러스성, 유전 등이 있으며 원인 불명인 경우도 있다.However, in modern society, due to an increase in noise exposure and an aging population, problems related to hearing loss due to cell or nerve damage rather than the above inflammation-based ear-related diseases have emerged. Moreover, most of the general public can distinguish the difference between ear-related diseases caused by inflammation such as bacterial otitis externa, malignant otitis, fungal otitis externa, otomycosis, otitis media, or otitis media, and diseases of hearing loss due to cell or nerve damage. Hearing loss is one of the most common diseases with a high incidence in modern society. Hearing loss due to damage to cells or nerves can be caused by ototoxic drugs, neurotoxic chemicals, viruses, genetics, etc., in addition to causes such as noise or aging, and there are cases where the cause is unknown.
이러한 난청의 치료를 위해서 다수의 전문의 및 의약 업계 관련 종사자들은 여전히 기존의 항생제 또는 항염증제에 기반을 둔 치료제로써 상기 질환을 치료하고자 목적하고 있으나, 이는 난청과 관련하여 적합한 치료제로 이용될 수 없다. 한편, 이와 같이 난청의 치료에 항생제 또는 항염증제 기반의 기존 치료제를 이용하는 것은, 첫 번째로 난청과 관련된 치료제가 알려진 것이 없기 때문이며, 두 번째로 난청에 대한 치료법에 대해 다수의 전문의 및 의약 업계 관련 종사자들이 명확히 인지하지 못하기 때문이다. 이러한 문제점에 의해 난청의 치료를 적절히 수행하지 못하는 문제점이 지속적으로 발생하고 있다. For the treatment of hearing loss, a number of specialists and pharmaceutical industry-related workers still aim to treat the disease as a therapeutic agent based on an existing antibiotic or anti-inflammatory agent, but this cannot be used as a suitable therapeutic agent for hearing loss. On the other hand, the use of antibiotics or anti-inflammatory drug-based existing therapeutic agents for the treatment of hearing loss is because, firstly, there is no known therapeutic agent for hearing loss, and secondly, a number of specialists and pharmaceutical industry-related practitioners regarding the treatment for hearing loss. because they are not clearly aware of it. Due to these problems, the problem that the treatment of hearing loss cannot be properly performed is continuously occurring.
특히, 항생제의 사용은 이독성을 가져 큰 문제점을 나타낸다. 예컨대, 아미노글리코사이드 항생제는 내이에서 청력과 평형 기능장애를 유발하는 이독성과 신장독성의 부작용을 가지고 있는데, 이는 과다복용뿐만 아니라 치료용량으로 장기간 복용시 발생할 수 있으며 일부에서는 단기간 적정용량에도 이독성이 발생하는 경우도 있다. 아미노글리코사이드 항생제 이독성은 사용자의 약 15%에서 전정기능 장애, 10-30%에서 청력감소를 보이며 주로 4000Hz 이상의 고주파수에서 급격한 고도난청의 형태로 양측 귀 모두에 발생한다.In particular, the use of antibiotics presents a major problem due to its ototoxicity. For example, aminoglycoside antibiotics have side effects of ototoxicity and nephrotoxicity that cause hearing and balance dysfunction in the inner ear. Sometimes this happens. The ototoxicity of aminoglycoside antibiotics shows vestibular dysfunction in about 15% of users and hearing loss in 10-30% of users.
이에 따라, 난청의 예방 및 치료에 효과적인 물질을 찾기 위한 연구로서 다양한 약물들에 대한 전임상 연구가 보고되고 있으나, 임상실험으로 진행하기에는 한계가 있음이 확인되었다. 또한, 현재까지 난청의 예방 및 치료와 관련하여 승인된 약물은 없다. 더욱이, 인체에 독성 또는 위험성 없이 사용할 수 있는 천연물 내지 천연 소재를 이용한 난청 치료제에 대해서는 개발된 약물을 거의 찾아볼 수 없다. 즉, 염증에 의해 유발되는 귀 관련 질환과 달리 난청에 대해 적합한 치료제가 전혀 개발되지 않은 실정이다. 이에 안정성이 확보된 천연 식물 소재 치료제의 개발이 요구된다. Accordingly, preclinical studies on various drugs have been reported as studies to find substances effective for prevention and treatment of hearing loss, but it has been confirmed that there is a limit to proceeding with clinical trials. In addition, there is no drug approved for the prevention and treatment of hearing loss to date. Moreover, there are hardly any developed drugs for hearing loss treatment using natural products or natural materials that can be used without toxicity or risk to the human body. That is, unlike ear-related diseases caused by inflammation, a suitable therapeutic agent for hearing loss has not been developed at all. Accordingly, there is a need for the development of a therapeutic agent made from natural plants that has secured stability.
본 발명이 해결하고자 하는 과제는 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올(3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol)을 유효성분으로 포함하는 난청(hearing loss) 예방 또는 치료용 약학적 조성물을 제공하는 것이다.The problem to be solved by the present invention includes 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol (3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol) as an active ingredient To provide a pharmaceutical composition for preventing or treating hearing loss.
본 발명이 해결하고자 하는 다른 과제는 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올을 유효성분으로 포함하는 난청 예방 또는 개선용 식품 조성물을 제공하는 것이다.Another object to be solved by the present invention is to provide a food composition for preventing or improving hearing loss comprising 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol as an active ingredient.
본 발명이 해결하고자 하는 다른 과제는 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올을 유효성분으로 포함하는 난청 예방 또는 개선용 사료 조성물을 제공하는 것이다.Another object to be solved by the present invention is to provide a feed composition for preventing or improving hearing loss comprising 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol as an active ingredient.
상기한 과제를 해결하기 위하여, 본 발명은 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올 (3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol), 이의 약제학적으로 허용 가능한 염, 용매화물, 호변체(tautomer), 수화물 또는 N-산화물을 유효성분으로 포함하는 난청(hearing loss) 예방 또는 치료용 약학적 조성물을 제공한다. In order to solve the above problems, the present invention provides 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol (3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol), its It provides a pharmaceutical composition for preventing or treating hearing loss (hearing loss) comprising a pharmaceutically acceptable salt, solvate, tautomer, hydrate or N- oxide as an active ingredient.
본 발명에 의하면, 상기 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올은 하기 화학식 1로 표시되는 화합물일 수 있다. According to the present invention, the 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol may be a compound represented by the following formula (1).
[화학식 1][Formula 1]
본 발명의 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올을 포함하는 약학적 조성물은 난청으로 인한 청력 역치의 상승과 유모세포 손상을 효과적으로 억제시킴으로써 난청에 우수한 치료 효과를 가진다.The pharmaceutical composition comprising 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol of the present invention has an excellent therapeutic effect on hearing loss by effectively inhibiting the increase in the hearing threshold and hair cell damage due to hearing loss. have
본 발명에서 "난청(hearing loss)"이란 청각이 저하 또는 상실된 모든 상태를 의미한다. 난청은 전음성 난청(conductive hearing loss) 및 감각신경성 난청(sensorineural hearing loss)을 포함할 수 있으나, 이에 제한되지 않는다.In the present invention, "hearing loss" means any state in which hearing is reduced or lost. Hearing loss may include, but is not limited to, conductive hearing loss and sensorineural hearing loss.
상기 전음성 난청은 귀 질환에 의한 난청으로, 소리를 전달하는 기관인 고막과 이소골 등의 기관에 문제가 생겨 발생하는 난청이다. 상기 난청은 여러 원인, 예컨대 감염, 손상, 염증, 종양 및 약물이나 기타 화학제에 대한 좋지 않은 반응에 의한 것일 수 있다.The conductive hearing loss is a hearing loss caused by an ear disease, and is a hearing loss caused by problems in organs such as the eardrum and ossicles, which are organs that transmit sound. The hearing loss can be due to several causes, such as infection, injury, inflammation, tumors, and a poor response to drugs or other chemicals.
상기 감각신경성 난청은 소리를 감지하는 기관인 달팽이관과 전기적 에너지로 소리를 전달하는 청신경, 그리고 소리의 변별, 이해 등 종합적인 역할을 하는 청각을 담당하는 뇌에 문제가 생겨 발생하는 난청이다. 감각신경성 난청의 원인은 소음, 약물, 노화, 외상 등에 의해 발생하는 난청일 수 있고, 예컨대 이독성 난청일 수 있다. 상기 이독성 난청은 이독성 약물인 젠타마이신(gentamicin), 스트렙토마이신(streptomycin), 가나마이신(kanamycin), 네오마이신(neomycin), 아미카신(amikacin), 토브라마이신(tobramycin), 네틸마이신(netilmicin), 디베카신(dibekacin), 시소마이신(sisomycin), 리보도마이신(livodomycin), 시스플라틴(cisplatin), 카르보플라틴(carboplatin) 및 옥살리플라틴(oxaliplatin)으로 구성된 군으로부터 선택된 어느 하나 이상의 약물의 투여로 인한 난청일 수 있다.The sensorineural hearing loss is a hearing loss caused by a problem in the cochlea, an organ that senses sound, the auditory nerve that transmits sound as electrical energy, and the brain responsible for hearing, which plays a comprehensive role in sound discrimination and understanding. The cause of sensorineural hearing loss may be hearing loss caused by noise, drugs, aging, trauma, or the like, for example, ototoxic hearing loss. The ototoxic hearing loss is ototoxic drugs gentamicin, streptomycin, kanamycin, neomycin, amikacin, tobramycin, netilmycin ( Administration of any one or more drugs selected from the group consisting of netilmicin), dibekacin, sisomycin, ribodomycin, cisplatin, carboplatin and oxaliplatin may be due to hearing loss.
또한, 상기 난청은 소음성 난청, 노인성 난청, 돌발성 난청, 당뇨병으로 인한 청신경병증, 이독성 난청, 외상성 난청, 바이러스성 난청 등을 포함할 수 있다.In addition, the hearing loss may include noise-induced hearing loss, age-related hearing loss, sudden hearing loss, auditory neuropathy due to diabetes, ototoxic hearing loss, traumatic hearing loss, viral hearing loss, and the like.
그러나, 청각이 저하 또는 상실된 상태에 해당한다면 본 발명의 상기 난청의 범주에 제한되지 않고 질환 범위로 포함될 수 있다.However, if it corresponds to a state in which hearing is impaired or lost, the scope of the present invention is not limited to the scope of hearing loss and may be included as a disease range.
본 발명에 의하면, 상기 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올은 약학적으로 허용가능한 염의 형태로 존재할 수 있다. 염으로는 약학적으로 허용가능한 유리산에 의해 형성된 산 부가염이 유용하다. 본 명세서에 사용된 바와 같이 "약학적으로 허용 가능한 염"이란 환자에게 비교적 비독성이고 무해한 유효작용을 갖는 농도로서 이 염에 기인한 부작용이 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올의 이로운 효능을 저하시키지 않는 임의의 모든 유기 또는 무기 부가염을 의미한다.According to the present invention, the 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol may be present in the form of a pharmaceutically acceptable salt. As the salt, an acid addition salt formed with a pharmaceutically acceptable free acid is useful. As used herein, "pharmaceutically acceptable salt" refers to a concentration having an effective action that is relatively non-toxic and harmless to a patient, and the side effects caused by this salt are 3,7-dihydroxy-5-methoxyphenylpropane. means any and all organic or inorganic addition salts which do not diminish the beneficial efficacy of -8,9-diol.
이때, 부가염으로서 무기산으로는 염산, 인산, 황산, 질산, 주석산 등을 사용할 수 있고, 유기산으로는 메탄설폰산, p-톨루엔설폰산, 아세트산, 트라이플루오로아세트산, 말레인산, 석신산, 옥살산, 벤조산, 타르타르산, 푸마르산, 만데르산, 프로피온산, 구연산, 젖산, 글리콜산, 글루콘산, 갈락투론산, 글루탐산, 글루타르산, 글루쿠론산, 아스파르트산, 아스코르브산, 카본산, 바닐릭산, 요오드화수소산 등을 사용할 수 있으며, 이들에 제한되지 않는다.In this case, as the addition salt, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, etc. can be used as inorganic acids, and as organic acids, methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, Benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid and the like may be used, but are not limited thereto.
또한, 염기를 사용하여 약학적으로 허용가능한 금속염을 만들 수 있다. 알칼리 금속염 또는 알칼리 토금속염은, 예를 들어 화합물을 과량의 알칼리 금속 수산화물 또는 알칼리 토금속 수산화물 용액 중에 용해시키고, 비용해 화합물 염을 여과한 후 여액을 증발, 건조시켜 얻는다. 이때, 금속염으로는 특히 나트륨, 칼륨, 칼슘, 마그네슘염 또는 이들의 혼합 염을 제조하는 것이 제약상 적합하나 이들에 제한되는 것은 아니다. In addition, a pharmaceutically acceptable metal salt can be prepared using a base. The alkali metal salt or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and then evaporating and drying the filtrate. In this case, it is pharmaceutically suitable to prepare a sodium, potassium, calcium, magnesium salt or a mixed salt thereof as the metal salt, but is not limited thereto.
본 발명에서 사용되는 용어, "예방"이란 본 발명에 따른 약학적 조성물의 투여에 의해 난청을 억제시키거나 난청의 발병을 지연시키는 모든 행위를 의미한다.As used herein, the term “prevention” refers to any act of suppressing hearing loss or delaying the onset of hearing loss by administering the pharmaceutical composition according to the present invention.
본 발명에서 사용되는 용어, "치료"란 본 발명에 따른 약학적 조성물의 투여에 의해 난청의 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.As used herein, the term “treatment” refers to any action in which the symptoms of hearing loss are improved or beneficially changed by administration of the pharmaceutical composition according to the present invention.
본 발명의 약학 조성물은 약학적으로 허용가능한 담체를 포함할 수 있으며, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제제화될 수 있다.The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier, and each of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., according to conventional methods, oral dosage forms, external preparations, suppositories, and It may be formulated in the form of a sterile injectable solution.
상기 약제학적으로 허용가능한 담체는 당업계에서 통상적으로 사용되는 것들, 예컨대 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등을 포함하나 이에 국한되지 않는다. 또한, 본 발명의 약학 조성물은 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제, 기타 약제학적으로 허용가능한 첨가제를 포함할 수 있으나, 이에 국한되지 않는다.The pharmaceutically acceptable carriers include those commonly used in the art, such as lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In addition, the pharmaceutical composition of the present invention may include diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, and other pharmaceutically acceptable additives, but is not limited thereto.
본 발명의 약학 조성물이 경구용 고형 제제로 제제화된 경우 정제, 환제, 산제, 과립제, 캡슐제 등을 포함하며, 이러한 고형제제는 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토즈, 젤라틴 등을 포함할 수 있으며, 마그네슘 스테아레이트, 탈크 같은 윤활제 등을 포함하나 이에 국한되지 않는다. When the pharmaceutical composition of the present invention is formulated as a solid preparation for oral use, it includes tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one or more excipients, for example, starch, calcium carbonate, It may include sucrose or lactose, gelatin, and the like, and includes, but is not limited to, lubricants such as magnesium stearate and talc.
본 발명의 약학 조성물이 경구용 액상 제제화된 경우 현탁제, 내용액제, 유제, 시럽제 등을 포함하며, 물, 리퀴드 파라핀 등의 희석제, 습윤제, 감미제, 방향제, 보존제 등을 포함하나 이에 국한되지 않는다. When the pharmaceutical composition of the present invention is formulated as a liquid formulation for oral use, it includes suspensions, solutions, emulsions, syrups, and the like, and includes, but is not limited to, water, diluents such as liquid paraffin, wetting agents, sweeteners, fragrances, preservatives, and the like.
본 발명의 약학 조성물이 비경구용 제제화된 경우 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제를 포함하며, 비수성 용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르류 등을 포함하나 이에 국한되지 않는다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있으나 이에 국한되지 않는다.When the pharmaceutical composition of the present invention is formulated for parenteral use, it includes sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories, and non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, olive. vegetable oils such as oils, injectable esters such as ethyl oleate, and the like. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, etc. may be used, but are not limited thereto.
상기 조성물은 약학적으로 유효한 양으로 단일 또는 다중 투여될 수 있다. 본 발명의 용어 "약학적으로 유효한 양"이란 의학적 예방 또는 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 예방 또는 치료하기에 충분한 양을 의미하며, 유효 용량 수준은 질환의 중증도, 약물의 활성, 환자의 연령, 체중, 건강, 성별, 환자의 약물에 대한 민감도, 사용된 본 발명 조성물의 투여 시간, 투여 경로 및 배출 비율, 치료기간, 사용된 본 발명의 조성물과 배합 또는 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 예를 들면, 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올은 1일 0.0001 내지 100 mg/kg으로, 바람직하게는 0.001 내지 10 mg/kg의 용량으로 투여할 수 있으며, 상기 투여는 하루에 한번 또는 수회 나누어 투여할 수도 있다.The composition may be administered singly or multiple times in a pharmaceutically effective amount. As used herein, the term "pharmaceutically effective amount" means an amount sufficient to prevent or treat a disease at a reasonable benefit/risk ratio applicable to medical prevention or treatment, and the effective dose level depends on the severity of the disease, the activity of the drug, Patient's age, weight, health, sex, patient's sensitivity to drug, administration time of the composition of the present invention used, administration route and excretion rate, treatment period, including drugs used in combination with or concurrently with the composition of the present invention factors and other factors well known in the medical art. For example, 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol may be administered at a dose of 0.0001 to 100 mg/kg per day, preferably 0.001 to 10 mg/kg per day. In addition, the administration may be administered once or divided several times a day.
본 발명의 약학 조성물은 랫트, 마우스, 가축, 인간 등의 포유동물 및 제브라피시 등 어류에 다양한 경로로, 예를 들면, 경구, 복강 또는 정맥, 근육, 피하, 자궁 내 경막 또는 뇌혈관 내 주사에 의해 투여될 수 있다.The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, and fish such as zebrafish by various routes, for example, oral, intraperitoneal or intravenous, intramuscular, subcutaneous, intrauterine dura mater or intracerebrovascular injection. can be administered by
본 발명의 약학 조성물은 조성물 총 중량에 대하여 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올을 0.01 내지 95 중량%, 바람직하게는 1 내지 80 중량%로 포함할 수 있다.The pharmaceutical composition of the present invention may contain 0.01 to 95% by weight, preferably 1 to 80% by weight of 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol, based on the total weight of the composition. have.
본 발명의 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올을 포함하는 약학적 조성물은 난청으로 인한 이상 행동의 감소시킴으로써 난청에 우수한 치료 효과를 가진다.The pharmaceutical composition comprising 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol of the present invention has an excellent therapeutic effect on hearing loss by reducing abnormal behavior due to hearing loss.
본 발명은 또한, 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올을 포함하는 약학적 조성물을 개체에게 투여하는 단계를 난청의 예방 또는 치료 방법을 제공한다. The present invention also provides a method for preventing or treating hearing loss by administering to a subject a pharmaceutical composition comprising 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol.
본 발명에서 용어 "3,7-디히드록시-5-메톡시페닐프로판-8,9-디올" 및 "난청"은 전술한 바와 같다.In the present invention, the terms "3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol" and "hearing loss" are the same as described above.
본 발명의 용어 "개체"란 난청이 발병하였거나 발병할 수 있는 동물을 말하며, 전형적으로 본 발명의 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올을 이용한 치료로 유익한 효과를 나타낼 수 있는 포유동물일 수 있다. 이러한 대상체의 바람직한 예로 인간과 같은 영장류가 포함될 수 있다. 또한 이와 같은 대상체들에는 난청을 갖거나 이와 같은 증상을 가질 위험이 있는 대상체들이 모두 포함될 수 있다. 전술한 바와 같이, 본 발명의 약학 조성물을 개체에게 투여함으로써 상기 난청을 효과적으로 예방 또는 치료할 수 있다. 본 발명의 약학 조성물은 개별 치료제로 투여하거나, 기존의 난청 치료제와 병용하여 투여될 수 있고, 종래의 치료제와는 순차적 또는 동시에 투여될 수 있다. As used herein, the term "individual" refers to an animal that has or may develop hearing loss, which is typically beneficial to treatment with the 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol of the present invention. It may be a mammal capable of exhibiting an effect. Preferred examples of such subjects may include primates such as humans. Also, such subjects may include all subjects who have hearing loss or are at risk of having such symptoms. As described above, by administering the pharmaceutical composition of the present invention to an individual, the hearing loss can be effectively prevented or treated. The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent, may be administered in combination with a conventional therapeutic agent for hearing loss, and may be administered sequentially or simultaneously with the conventional therapeutic agent.
본 발명의 용어 "투여"란 적절한 방법으로 환자에게 소정의 물질을 도입하는 것을 의미하며 상기 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 어떠한 일반적인 경로를 통하여 투여될 수 있다. 또한, 본 발명의 약학 조성물은 활성 물질이 목적 조직으로 이동할 수 있는 임의의 장치에 의해 투여될 수도 있다. 예를 들면, 경구 투여, 복강내 투여, 정맥내 투여, 근육내 투여, 피하 투여, 피내 투여, 경구 투여, 국소 투여, 비내 투여, 폐내 투여, 직장내 투여될 수 있으나, 이에 제한되지는 않는다. 경구 투여를 위한 고형 제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다.The term "administration" of the present invention means introducing a predetermined substance to a patient by an appropriate method, and the administration route of the composition may be administered through any general route as long as it can reach a target tissue. In addition, the pharmaceutical composition of the present invention may be administered by any device capable of transporting the active substance to a target tissue. For example, oral administration, intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, topical administration, intranasal administration, intrapulmonary administration, may be administered intrarectally, but is not limited thereto. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories.
본 발명의 약학적 조성물의 투여는 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있다. 상기 요소를 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양으로 투여할 수 있으며, 이는 당업자에 의해 용이하게 결정될 수 있다.Administration of the pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or may be administered in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. Taking all of the above factors into consideration, it can be administered in an amount that can obtain the maximum effect with a minimum amount without side effects, which can be easily determined by those skilled in the art.
본 발명은 또한 난청의 예방 또는 치료를 위한 의약을 제조하기 위한 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올의 용도를 제공한다.The present invention also provides the use of 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol for the manufacture of a medicament for the prevention or treatment of hearing loss.
본 발명은 또한 난청의 예방 또는 치료에 사용하기 위한 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올을 포함하는 조성물을 제공한다.The present invention also provides a composition comprising 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol for use in the prevention or treatment of hearing loss.
본 발명은 또한 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올, 이의 약제학적으로 허용 가능한 염, 용매화물, 호변체(tautomer), 수화물 또는 N-산화물을 유효성분으로 포함하는 난청의 예방 또는 개선용 식품 조성물을 제공한다.The present invention also provides 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol, a pharmaceutically acceptable salt, solvate, tautomer, hydrate or N- oxide thereof as an active ingredient. It provides a food composition for preventing or improving hearing loss comprising a.
본 발명의 용어, “개선”이란, 본 발명의 조성물의 투여로 난청이 호전 또는 이롭게 변경되는 모든 행위를 의미한다.As used herein, the term “improvement” refers to any action in which hearing loss is improved or beneficially changed by administration of the composition of the present invention.
본 발명에서 용어 "3,7-디히드록시-5-메톡시페닐프로판-8,9-디올" 및 "난청"은 전술한 바와 같다.In the present invention, the terms "3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol" and "hearing loss" are the same as described above.
본 발명의 식품 조성물은 통상의 식품 첨가물을 포함할 수 있으며, 상기 "식품 첨가물"로서의 적합 여부는 다른 규정이 없는 한, 식품의약품안전처에 승인된 식품 첨가물 공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다. The food composition of the present invention may contain conventional food additives, and the suitability as the "food additive" is determined according to the general rules and general test methods of food additives approved by the Ministry of Food and Drug Safety, unless otherwise specified. It is judged according to the standards and standards related to the item.
상기 "식품 첨가물 공전"에 수재된 품목으로는 예를 들어, 케톤류, 글리신, 구연산칼륨, 니코틴산, 계피산 등의 화학적 합성물, 감색소, 감초추출물, 결정셀룰로오스, 고량색소, 구아검 등의 천연첨가물, L-글루타민산나트륨 제제, 면류첨가알칼리제, 보존료제제, 타르색소제제 등의 혼합제제류들을 들 수 있다.The items listed in the "Food Additives Code" include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid; Mixed preparations such as sodium L-glutamate preparation, noodle-added alkali agent, preservative agent, and tar color agent can be mentioned.
또한, 본 발명의 식품 조성물은 난청의 예방 및/또는 개선을 목적으로, 정제, 캡슐, 분말, 과립, 액상, 환 등의 형태로 제조 및 가공할 수 있다.In addition, the food composition of the present invention may be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. for the purpose of preventing and/or improving hearing loss.
본 발명의 식품 조성물은 건강기능식품으로서 사용될 수 있다. 상기 "건강기능식품"이라 함은 건강기능식품에 관한 법률에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 의미하며, "기능성"이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건 용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다.The food composition of the present invention can be used as a health functional food. The term "health functional food" means a food manufactured and processed using raw materials or ingredients useful for the human body in accordance with the Health Functional Food Act, and "functionality" refers to the structure and function of the human body. It refers to ingestion for the purpose of obtaining useful effects for health purposes such as regulating nutrients or physiological effects.
예를 들어, 상기 정제 형태의 건강기능식품은 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올, 부형제, 결합제, 붕해제, 및 다른 첨가제와의 혼합물을 통상의 방법으로 과립화한 다음, 활택제 등을 넣어 압축성형하거나, 상기 혼합물을 직접 압축성형할 수 있다. 또한, 상기 정제 형태의 건강기능식품은 필요에 따라 교미제 등을 함유할 수 있으며, 필요에 따라 적당한 제피제로 제피할 수도 있다.For example, the health functional food in tablet form is prepared by mixing 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol, excipients, binders, disintegrants, and other additives in a conventional manner. After granulation with a lubricating agent, etc., compression molding, or the mixture can be directly compression molded. In addition, the health functional food in the form of tablets may contain a mating agent, etc., if necessary, and may be coated with a suitable skinning agent if necessary.
캡슐 형태의 건강기능식품 중 경질캡슐제는 통상의 경질캡슐에 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올, 및 부형제 등의 첨가제와의 혼합물 또는 그의 입상물 또는 제피한 입상물을 충진하여 제조할 수 있으며, 연질캡슐제는 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올 부형제 등의 첨가제와의 혼합물을 젤라틴 등 캡슐기제에 충진하여 제조할 수 있다. 상기 연질캡슐제는 필요에 따라 글리세린 또는 소르비톨 등의 가소제, 착색제, 보존제 등을 함유할 수 있다.Among the health functional foods in the form of capsules, hard capsules are a mixture of 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol, and additives such as excipients, or granular materials thereof, or It can be prepared by filling the skinned granular material, and the soft capsule is filled with a mixture of additives such as 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol excipient in a capsule base such as gelatin. can be manufactured. The soft capsule formulation may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, if necessary.
환 형태의 건강기능식품은 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올, 부형제, 결합제, 붕해제 등의 혼합물을 적당한 방법으로 성형하여 조제할 수 있으며, 필요에 따라 백당이나 다른 적당한 제피제로 제피를, 또는 전분, 탈크 또는 적당한 물질로 환의를 입힐 수도 있다.A health functional food in the form of a ring can be prepared by molding a mixture of 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol, excipients, binders, disintegrants, etc. by an appropriate method, and if necessary Depending on the circumstances, the skin may be coated with sucrose or other suitable skinning agent, or may be coated with starch, talc or a suitable material.
과립 형태의 건강기능식품은 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올, 부형제, 결합제, 붕해제 등의 혼합물을 적당한 방법으로 입상으로 제조할 수 있으며, 필요에 따라 착향제, 교미제 등을 함유할 수 있다. 과립형태의 건강기능식품은 12호(1680 μm), 14호(1410 μm) 및 45호(350 μm) 체를 써서 다음 입도시험을 할 때에 12호체를 전량 통과하고 14호체에 남는 것이 전체량의 5.0 %이하이고 또 45호체를 통과하는 것은 전체량의 15.0 %이하일 수 있다.Health functional food in granular form can be prepared in granular form by a suitable method by mixing a mixture of 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol, excipients, binders, and disintegrants. It may contain flavoring agents, flavoring agents, and the like. For health functional foods in granular form, use No. 12 (1680 μm), No. 14 (1410 μm), and No. 45 (350 μm) sieves to pass the entire amount of sieve No. 12 and remain in No. 14 when the next particle size test is performed. 5.0% or less and passing through No. 45 may be less than 15.0% of the total amount.
상기 부형제, 결합제, 붕해제, 활택제, 교미제, 착향제 등에 대한 용어 정의는 당업계에 공지된 문헌에 기재된 것으로 그 기능 등이 동일 내지 유사한 것들을 포함한다(대한약전 해설편, 문성사, 한국약학대학협의회, 제 5 개정판, p33-48, 1989).The term definitions for the excipients, binders, disintegrants, lubricants, flavoring agents, flavoring agents, etc. are described in documents known in the art and include those having the same or similar functions (Explanation of the Korean Pharmacopoeia, Moonseongsa, Korea) Association of Colleges of Pharmacy, 5th ed., p33-48, 1989).
상기 식품의 종류에는 특별한 제한이 없으며, 본 발명의 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올을 첨가할 수 있는 식품의 예로는 음료, 껌, 비타민 복합제, 드링크제 등이 있으며, 통상적인 의미에서의 건강기능식품을 모두 포함한다.There is no particular limitation on the type of the food, and examples of the food to which the 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol of the present invention can be added include beverages, gums, vitamin complexes, and drinks. etc., and includes all health functional foods in the ordinary sense.
본 발명의 식품 조성물은 조성물 총 중량에 대하여 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올을 0.01 내지 95 중량%, 바람직하게는 1 내지 80 중량%로 포함할 수 있다. The food composition of the present invention may contain 0.01 to 95% by weight, preferably 1 to 80% by weight of 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol, based on the total weight of the composition. have.
본 발명의 또 하나의 양태는 상기 식품 조성물을 포함하는 건강기능식품을 제공한다. 상기 식품 조성물 및 건강기능식품은 전술한 바와 같다.Another aspect of the present invention provides a health functional food comprising the food composition. The food composition and health functional food are the same as described above.
또한, 본 발명은 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올, 이의 약제학적으로 허용 가능한 염, 용매화물, 호변체(tautomer), 수화물 또는 N-산화물을 포함하는 난청의 예방 또는 개선용 사료 조성물을 제공한다. The present invention also includes 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol, a pharmaceutically acceptable salt, solvate, tautomer, hydrate or N- oxide thereof. It provides a feed composition for preventing or improving hearing loss.
본 발명에 있어서 상기 사료는 어류, 조류 또는 포유류의 사료 일 수 있으며, 바람직하게, 축산법 제2조 제1호 및 동법 시행규칙 제2조 각호에서 정의하고 있는, 야생습성이 순화되어 사육하기에 적합하며 농가의 소득증대에 기여할 수 있는 가축 또는 수산생물의 사료일 수 있다. 상기 가축에는 소, 말, 노새, 당나귀, 염소, 산양, 면양, 사슴, 돼지, 토끼, 가금류 등일 수 있으며, 가금류에는 닭, 칠면조, 오리, 타조, 거위, 메추리 등, 바람직하게는 닭일 수 있으나, 사육하여 축산물을 얻기에 적합한 것이라면 이에 제한되는 것은 아니다. 상기 "축산물"은 축산법 제2조 3호의 정의인, 가축에서 생산된 고기, 젖, 알, 꿀과 이들의 가공품, 원피 (원모피를 포함한다), 원모, 기타 가축의 생산물로서 농림부령이 정하는 것을 의미한다. 또한 반려동물을 포함하여 개, 고양이 등일 수 있으나, 이에 제한되는 것은 아니다.In the present invention, the feed may be a feed for fish, birds or mammals, and preferably, it is suitable for breeding as its wild habits are acclimatized, as defined in Article 2 No. 1 of the Livestock Act and Article 2 of the Enforcement Rule of the same Act. and may be feed for livestock or aquatic organisms that can contribute to the increase of farm household income. The livestock may include cattle, horses, mules, donkeys, goats, goats, sheep, deer, pigs, rabbits, poultry, etc., and the poultry includes chickens, turkeys, ducks, ostriches, geese, quails, etc., preferably chickens, If it is suitable for breeding and obtaining livestock products, it is not limited thereto. The above "livestock products" are meat, milk, eggs, honey and their processed products, raw hides (including raw fur), raw wool, and other livestock products, which are defined by Article 2, 3 of the Livestock Act, as determined by the Ordinance of the Ministry of Agriculture and Forestry. means that In addition, it may be a dog, a cat, etc., including companion animals, but is not limited thereto.
발명의 용어 "사료"는 동물이 먹고, 섭취하며, 소화시키기 위한 또는 이에 적당한 임의의 천연 또는 인공 규정식, 한끼식 등 또는 상기 한끼식의 성분을 의미한다. 일 양태로, 본 발명의 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올을 함유하는 사료용 조성물에는 농후사료, 조사료 및/또는 특수사료가 포함될 수 있다.The term "feed" in the present invention means any natural or artificial diet, meal, etc., or a component of said meal, intended for or suitable for being eaten, consumed, and digested by an animal. In one aspect, the composition for feed containing 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol of the present invention may include a concentrated feed, roughage and/or special feed.
농후사료에는 밀, 귀리, 옥수수 등의 곡류를 포함하는 종자열매류, 곡물을 정제하고 얻는 부산물로서 쌀겨, 밀기울, 보릿겨 등을 포함하는 겨류, 콩, 유체, 깨, 아마인, 코코야자 등을 채유하고 얻는 부산물인 깻묵류와 고구마, 감자 등에서 녹말을 뺀 나머지인 녹말찌꺼기의 주성분인 잔존녹말질류 등의 찌꺼기류, 어분, 물고기찌꺼기, 어류에서 얻은 신선한 액상물을 농축시킨 것인 피시솔루블, 육분, 혈분, 우모분, 탈지분유, 우유에서 치즈, 탈지유에서 카제인을 제조할 때의 잔액인 훼이(whey)를 건조한 건조훼이 등의 동물질사료, 효모, 클로렐라, 해조류 등이 있다.In the enriched feed, seed fruits containing grains such as wheat, oats, and corn, bran containing rice bran, bran, barley bran, etc. Fish-soluble, meat powder, which is a concentrated product of fish meal, fish waste, and fresh liquids obtained from fish meal, fish waste, and residual starch, which is the main component of starch residue, which is the remainder of starch residue obtained by subtracting starch from sweet potatoes and potatoes. , animal feed such as dried whey, yeast, chlorella, seaweed, etc., which are dried whey, which is the remainder of the production of casein from milk, cheese, and casein from skim milk.
조사료에는 야초, 목초, 풋베기 등의 생초(生草)사료, 사료용 순무, 사료용 비트, 순무의 일종인 루터베어거 등의 뿌리채소류, 생초, 풋베기작물, 곡실(穀實)등을 사일로에 채워 놓고 젖산발효시킨 저장사료인 사일리지(silage), 야초, 목초를 베어 건조시킨 건초, 종축용(種畜用) 작물의 짚, 콩과 식물의 나뭇잎 등이 있다. 특수 사료에는 굴껍떼기, 암염 등의 미네랄 사료, 요소나 그 유도체인 디우레이드이소부탄 등의 요소사료, 천연사료 원료만을 배합했을 때 부족하기 쉬운 성분을 보충하거나, 사료의 저장성을 높이기 위해서 배합사료에 미량으로 첨가하는 물질인 사료첨가물 등이 있다.For roughage, raw grass feed such as wild grasses, grasses, and green cuttings, turnips for feed, beets for feed, root vegetables such as ruther beargers, a type of turnip, raw herbs, green crops, grains, etc. are placed in a silo. There are silage, which is stored feed fermented with lactic acid, wild grass, hay dried after cutting grass, straw for breeding crops, and leaves from legumes. Special feed includes mineral feed such as oyster shells and rock salt, urea feed such as urea or its derivative diureide isobutane, and supplementation of ingredients that are likely to be lacking when only natural feed ingredients are mixed, or added to formulated feed to increase feed storage. There are feed additives, which are substances added in trace amounts.
본 발명의 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올, 이의 약제학적으로 허용 가능한 염, 용매화물, 호변체(tautomer), 수화물 또는 N-산화물을 포함하는 조성물은 난청으로 인한 청력상승은 물론 항생제 사용에 의해 유발되는 유모세포의 손상을 효과적으로 억제할 수 있으므로, 난청 특히, 이독성 난청의 예방, 치료 또는 개선에 유용하므로 약학적 조성물 또는 건강기능식품으로 유용하게 사용될 수 있다.Composition comprising 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol of the present invention, a pharmaceutically acceptable salt, solvate, tautomer, hydrate or N- oxide thereof is useful for preventing, treating or improving hearing loss, especially ototoxic hearing loss, as it can effectively inhibit not only the increase in hearing caused by hearing loss but also the hair cell damage caused by the use of antibiotics, it is useful as a pharmaceutical composition or health functional food. can be used
도 1은 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올의 네오마이신 처리에 의한 유모세포 손상에 대한 억제 효과를 나타낸 도이다. NOR은 네오마이신 미처리 정상 대조군을, NM은 네오마이신만을 처리한 비교군을, DMP는 1 μg/mL 농도로 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올을 처리한 실험군을 나타낸다.1 is a diagram showing the inhibitory effect on hair cell damage by neomycin treatment of 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol. NOR is a normal control untreated with neomycin, NM is a control group treated with only neomycin, and DMP is treated with 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol at a concentration of 1 μg/mL. represents one experimental group.
본 발명자들은 안전성이 확보된, 천연 식물 소재 예컨대, 식품 또는 약제의 소재로 손쉽게 사용될 수 있는 소재로부터 난청 예방 또는 치료 효과를 갖는 물질을 발굴하기 위하여 예의 연구 노력한 결과, 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올(3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol)이 항생제에 의한 손상으로부터 유모세포를 보호하는 효과를 나타냄을 확인하고, 본 발명을 완성하였다. The present inventors have made intensive research efforts to discover a substance having a preventive or therapeutic effect for hearing loss from a natural plant material that has secured safety, such as a material that can be easily used as a material for food or pharmaceuticals. As a result, 3,7-dihydroxy- Confirming that 5-methoxyphenylpropane-8,9-diol (3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol) exhibits the effect of protecting hair cells from damage caused by antibiotics, the present invention completed.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 예시하기 위한 것으로서, 본 발명의 범위가 이들 실시예에 의해 제한되는 것으로 해석되지는 않는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not to be construed as being limited by these examples.
실시예Example
제조예 1. 이독성 난청 제브라피시 모델의 준비Preparation Example 1. Preparation of ototoxic deafness zebrafish model
수정 6일 후의 제브라피시 치어(larvae)를 24웰에 위치시킨 후, 네오마이신을 2 μM 농도로 처리하여 1시간 동안 노출시켜 이독성 난청 모델을 제조하였다. 이와 함께 네오마이신을 처리하지 않은 미처리 정상 대조군을 준비하였다.After 6 days of fertilization, zebrafish larvae were placed in 24 wells, treated with neomycin at a concentration of 2 μM and exposed for 1 hour to prepare an ototoxic hearing loss model. In addition, an untreated normal control group not treated with neomycin was prepared.
실시예 1: 이독성 난청 제브라피시 모델에 대한 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올의 효과Example 1: Effect of 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol on ototoxic deafness zebrafish model
상기 제조예 1에 따라 준비한 이독성 난청 제브라피시 모델에 상기 제조예 준비한 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올을 1 μg/mL 농도로 처리하여 6시간 동안 노출시켰다. 비교군으로는 0.03% 해수염용액(sea salt solution)을 사용하였다. 제조예 1에 따라 준비한 정상 대조군 및 제조예 1의 이독성 난청 모델에 각각 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올 및 해수염용액을 처리한 실험군과 비교군의 제브라피시 치어를 0.02% 트리카인으로 마취시키고, 유모세포를 0.1% YO-PRO로 30분 동안 염색하여, 형광현미경(Olympus 1×70, Olympus, Japan)을 사용하여 육안으로 직접 관찰하였다. 구체적으로, 육안으로 관찰되는 유모세포의 갯수를 세어 그래프로 작성하고, 형광 이미지를 사진으로 찍어 도 1에 나타내었다.The ototoxic deafness zebrafish model prepared according to Preparation Example 1 was treated with the 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol prepared in Preparation Example at a concentration of 1 μg/mL for 6 hours. exposed. As a comparison group, a 0.03% sea salt solution was used. The normal control group prepared according to Preparation Example 1 and the experimental group and control group treated with 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol and sea salt solution to the ototoxic hearing loss model of Preparation Example 1, respectively of zebrafish fry were anesthetized with 0.02% tricaine, and hair cells were stained with 0.1% YO-PRO for 30 minutes, and directly observed with the naked eye using a fluorescence microscope (Olympus 1×70, Olympus, Japan). Specifically, a graph was prepared by counting the number of hair cells observed with the naked eye, and the fluorescence image was taken as a photograph and shown in FIG. 1 .
도 1에 나타난 바와 같이, 정상 대조군에 비해 이독성 난청 유도 제브라피시 모델에 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올을 처리하지 않은 비교군에서는 유모세포의 갯수가 현저하게 감소한 반면, 상기 이독성 난청 유도 제프라피시에 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올을 처리한 실험군에서는 유모세포의 갯수가 유의적으로 증가하였다. 이를 통해 3,7-디히드록시-5-메톡시페닐프로판-8,9-디올의 처리가 이독성 난청에 의한 유모세포 손상을 감소시켜 난청의 예방 및 치료에 효과가 있음을 확인하였다.As shown in FIG. 1, the number of hair cells in the comparative group that was not treated with 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol in the ototoxic deafness-induced zebrafish model compared to the normal control group. was significantly decreased, whereas the number of hair cells was significantly increased in the experimental group treated with 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol in the ototoxic deafness-induced zeprafish. . Through this, it was confirmed that the treatment of 3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol was effective in preventing and treating hearing loss by reducing hair cell damage caused by ototoxic hearing loss.
제제예 1: 정제의 제조Formulation Example 1: Preparation of tablets
3,7-디히드록시-5-메톡시페닐프로판-8,9-디올 1000 mg3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol 1000 mg
유당 100 mglactose 100 mg
전분 100 mgstarch 100 mg
스테아린산 마그네슘 적량magnesium stearate appropriate amount
통상의 정제 제조방법에 따라 상기 조성으로 각 성분을 혼합하고 타정하여 정제를 제조하였다.According to a conventional tablet manufacturing method, each component was mixed with the above composition and tableted to prepare a tablet.
제제예 2: 액제의 제조Formulation Example 2: Preparation of liquid formulation
3,7-디히드록시-5-메톡시페닐프로판-8,9-디올 1000 mg3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol 1000 mg
CMC-Na 20 gCMC-Na 20 g
이성화당 20 gLee Seonghwadang 20 g
레몬향 적량lemon flavor appropriate amount
정제수 총 1000 mL까지Purified water up to 1000 mL total
통상의 액제 제조방법에 따라 상기 조성으로 각 성분을 혼합한 다음, 갈색병에 충전하고 멸균시켜 액제를 제조하였다.After mixing each component with the above composition according to a conventional liquid preparation method, it was filled in a brown bottle and sterilized to prepare a liquid preparation.
제제예 3: 캡슐제의 제조Formulation Example 3: Preparation of capsules
3,7-디히드록시-5-메톡시페닐프로판-8,9-디올 1000 mg3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol 1000 mg
결정성 셀룰로오스 3 mgcrystalline cellulose 3 mg
락토오스 14.8 mglactose 14.8 mg
마그네슘 스테아레이트 0.2 mgmagnesium stearate 0.2 mg
통상의 캡슐제 제조방법에 따라 상기 조성으로 각 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.According to a conventional capsule preparation method, each component was mixed with the above composition and filled in a gelatin capsule to prepare a capsule.
제제예 4: 주사제의 제조Formulation Example 4: Preparation of injection
3,7-디히드록시-5-메톡시페닐프로판-8,9-디올 1000 mg3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol 1000 mg
만니톨 180 mgmannitol 180 mg
주사용 멸균 증류수 2974 mgSterile distilled water for injection 2974 mg
Na2HPO412H2O 26 mgNa 2 HPO 4 12H 2 O 26 mg
통상의 주사제 제조방법에 따라 2 mL 용량의 앰플 당 상기 조성으로 각 성분을 함유하도록 주사제를 제조하였다.An injection was prepared to contain each component in the above composition per ampoule of 2 mL volume according to a conventional injection preparation method.
제제예 5: 건강기능성 음료의 제조Formulation Example 5: Preparation of health functional beverage
3,7-디히드록시-5-메톡시페닐프로판-8,9-디올 1000 mg3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol 1000 mg
구연산 1000 mgcitric acid 1000 mg
올리고당 100 goligosaccharide 100 g
매실농축액 2 gPlum Concentrate 2 g
정제수 총 900 mL까지Purified water up to 900 mL total
통상의 건강기능성 음료 제조방법에 따라 상기 조성으로 각 성분을 혼합하여 건강기능성 음료를 제조하였다.According to a conventional health functional beverage manufacturing method, each component was mixed with the above composition to prepare a health functional beverage.
Claims (11)
3,7-디히드록시-5-메톡시페닐프로판-8,9-디올은 하기 화학식 1의 구조를 갖는 것인, 약학적 조성물:
[화학식 1]
3,7-dihydroxy-5-methoxyphenylpropane-8,9-diol is a pharmaceutical composition having the structure of Formula 1 below:
[Formula 1]
상기 난청은 전음성 난청(conductive hearing loss) 또는 감각신경성 난청(sensorineural hearing loss)인, 약학적 조성물.According to claim 1,
Wherein the hearing loss is conductive hearing loss or sensorineural hearing loss.
상기 난청은 소음성 난청, 노인성 난청, 돌발성 난청, 당뇨병으로 인한 청신경병증, 이독성 난청, 외상성 난청 및 바이러스성 난청으로 이루어진 군으로부터 선택되는 어느 하나인, 약학적 조성물.According to claim 1,
The hearing loss is any one selected from the group consisting of noise-induced deafness, senile deafness, sudden deafness, auditory neuropathy due to diabetes, ototoxic deafness, traumatic deafness and viral deafness, a pharmaceutical composition.
상기 난청은 전음성 난청 또는 감각신경성 난청인, 식품 조성물.6. The method of claim 5,
The hearing loss is conductive hearing loss or sensorineural hearing loss, the food composition.
상기 난청은 소음성 난청, 노인성 난청, 돌발성 난청, 당뇨병으로 인한 청신경병증, 이독성 난청, 외상성 난청 및 바이러스성 난청으로 이루어진 군으로부터 선택되는 어느 하나인, 식품 조성물. 6. The method of claim 5,
The hearing loss is any one selected from the group consisting of noise-induced deafness, senile deafness, sudden deafness, auditory neuropathy due to diabetes, ototoxic deafness, traumatic deafness and viral deafness, the food composition.
상기 난청은 전음성 난청 또는 감각신경성 난청인, 사료 조성물. 10. The method of claim 9,
The hearing loss is conductive hearing loss or sensorineural hearing loss, feed composition.
상기 난청은 소음성 난청, 노인성 난청, 돌발성 난청, 당뇨병으로 인한 청신경병증, 이독성 난청, 외상성 난청 및 바이러스성 난청으로 이루어진 군으로부터 선택되는 어느 하나인, 사료 조성물. 10. The method of claim 9,
The hearing loss is any one selected from the group consisting of noise-induced deafness, senile deafness, sudden deafness, auditory neuropathy due to diabetes, ototoxic deafness, traumatic deafness and viral deafness, the feed composition.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2024154959A1 (en) * | 2023-01-17 | 2024-07-25 | 고려대학교 산학협력단 | Pharmaceutical composition containing dexpanthenol as active ingredient for preventing or treating hearing loss |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101367479B1 (en) | 2008-07-21 | 2014-03-14 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | Controlled release antimicrobial compositions and methods for the treatment of otic disorders |
| KR101777157B1 (en) | 2010-03-01 | 2017-09-26 | 라보라토리오스 살바트, 에스.에이. | Aqueous clear solutions of Fluocinolone Acetonide for treatment of otic inflammation |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR101367479B1 (en) | 2008-07-21 | 2014-03-14 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | Controlled release antimicrobial compositions and methods for the treatment of otic disorders |
| KR101777157B1 (en) | 2010-03-01 | 2017-09-26 | 라보라토리오스 살바트, 에스.에이. | Aqueous clear solutions of Fluocinolone Acetonide for treatment of otic inflammation |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024154959A1 (en) * | 2023-01-17 | 2024-07-25 | 고려대학교 산학협력단 | Pharmaceutical composition containing dexpanthenol as active ingredient for preventing or treating hearing loss |
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