WO2024091014A1 - 암모늄 락테이트를 유효성분으로 포함하는 난청 예방 또는 치료용 약학 조성물 - Google Patents
암모늄 락테이트를 유효성분으로 포함하는 난청 예방 또는 치료용 약학 조성물 Download PDFInfo
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- WO2024091014A1 WO2024091014A1 PCT/KR2023/016730 KR2023016730W WO2024091014A1 WO 2024091014 A1 WO2024091014 A1 WO 2024091014A1 KR 2023016730 W KR2023016730 W KR 2023016730W WO 2024091014 A1 WO2024091014 A1 WO 2024091014A1
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- WIPO (PCT)
- Prior art keywords
- hearing loss
- ammonium lactate
- pharmaceutical composition
- active ingredient
- preventing
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/30—Other Organic compounds
Definitions
- the present invention provides a pharmaceutical composition for preventing or treating hearing loss containing ammonium lactate as an active ingredient.
- Gentamycin has been widely used as an excellent antibiotic for a long time and is a drug approved by the U.S. Food and Drug Administration. It is an amino glucoside antibiotic produced by micromonospora purprea and micromonospora echinospora and is a mixture of gentamicins C1, C2, and C1a. It is effective against Staphylococcus aureus among gram-positive bacteria, E. coli, Salmonella, and Pseudomonas aeruginosa among gram-negative bacteria. Gentamicin is also used in the treatment of enterococcal endocarditis along with penicillin or ampicillin. It is administered parenterally or is often used as an external agent.
- gentamicin can completely block the progression of Duchenne muscular dystrophy, which can benefit from antibiotic administration.
- permanent hearing loss and kidney damage are known to be typical side effects.
- Ototoxic hearing loss is a side effect that occurs due to the use of ototoxic drugs, and aminoglycoside antibiotics and some anticancer drugs are known to cause ototoxicity.
- Aminoglycoside antibiotics exhibit antibacterial activity by binding to the bacterial 30s ribosomal subunit and inhibiting protein synthesis. When these aminoglycoside antibiotics are continuously exposed to cochlear cells, they cause damage to the outer hair cells of the organ of Corti. hair cells and sensory hair cells die (apoptosis). The death mechanism is known to be caused by reactive oxygen species (ROS) formed by aminoglycoside antibiotics and Ca++ complexes.
- ROS reactive oxygen species
- the purpose of the present invention is to provide a pharmaceutical composition for preventing or treating hearing loss containing ammonium lactate as an active ingredient.
- Another object of the present invention is to provide a health functional food composition for preventing or improving hearing loss containing ammonium lactate as an active ingredient.
- the present invention provides a pharmaceutical composition for preventing or treating hearing loss containing ammonium lactate as an active ingredient.
- the present invention provides a health functional food composition for preventing or improving hearing loss containing ammonium lactate as an active ingredient.
- compositions containing active ingredients can be used to prevent or treat hearing loss, a side effect caused by using the antibiotic ammonium lactate.
- Figure 1 shows the molecular structure of ammonium lactate.
- Figure 2 shows the results of confirming the number of hair cells in zebrafish according to administration of ammonium lactate.
- Figure 3 shows the results of confirming the survival rate of zebrafish hair cells according to ammonium lactate administration.
- the present invention provides a pharmaceutical composition for preventing or treating hearing loss containing ammonium lactate as an active ingredient.
- the hearing loss may be one or more of the group consisting of ototoxic hearing loss, sudden hearing loss, noise-induced hearing loss, and age-related hearing loss.
- the ototoxic hearing loss may be hearing loss caused by anticancer drugs or aminoglucoside antibiotics.
- the anticancer agent may be cisplatin or carboplatin.
- the aminoglucoside antibiotics include amikacin, arbekacin, kanamycin, gentamicin, neomycin, netilmicin, and dibekacin. , sisomycin, streptomycin, tobramycin, ribodomycin, and paromomycin.
- the pharmaceutical composition may contain suitable carriers, excipients, disintegrants, sweeteners, coating agents, bulking agents, lubricants, lubricants, flavoring agents, antioxidants, buffers, bacteriostatic agents, etc. commonly used in the preparation of pharmaceutical compositions. It may further include one or more additives selected from the group consisting of diluents, dispersants, surfactants, binders, and lubricants.
- carriers, excipients, and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, and microcrystalline.
- Cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil can be used.
- Solid preparations for oral administration include tablets, pills, powders, granules, and capsules.
- Such solid preparations can be prepared by mixing the composition with at least one or more excipients, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc.
- excipients such as starch, calcium carbonate, sucrose or lactose, gelatin, etc.
- lubricants such as magnesium styrate and talc can also be used.
- Liquid preparations for oral use include suspensions, oral solutions, emulsions, and syrups.
- various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included.
- Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, etc.
- Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate.
- injectable ester such as ethyl oleate.
- As a base for suppositories witepsol, macrogol, tween 61, cacao, laurin, glycerogeratin, etc. can be used.
- the pharmaceutical composition is intravenous, intraarterial, intraperitoneal, intramuscular, intraarterial, intraperitoneal, intrasternal, transdermal, intranasal, inhalational, topical, rectal, oral, intraocular or It can be administered to a subject in a conventional manner via the intradermal route.
- the dosage of the active ingredient according to the present invention may vary depending on the subject's condition and weight, type and degree of disease, drug form, administration route and period, and may be appropriately selected by a person skilled in the art, and the daily dosage is 0.01 mg. /kg to 200 mg/kg, preferably 0.1 mg/kg to 200 mg/kg, more preferably 0.1 mg/kg to 100 mg/kg.
- Administration may be administered once a day or divided into several administrations, and the scope of the present invention is not limited thereby.
- the present invention provides a health functional food composition for preventing or improving hearing loss containing ammonium lactate as an active ingredient.
- the health functional food includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavors, colorants and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, It may contain organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. Additionally, it may contain pulp for the production of natural fruit juice, synthetic fruit juice, and vegetable drinks. These ingredients can be used independently or in combination.
- the health functional food composition may be in the form of any one of meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, gum, ice cream, soup, beverages, tea, functional water, drink, alcohol, and vitamin complex. It can be.
- the above-mentioned health functional food may additionally contain food additives, and its suitability as a “food additive” is determined according to the general provisions and general test methods of the Food Additive Code approved by the Food and Drug Administration, unless otherwise specified. Determination is made according to relevant standards and standards.
- Items listed in the "Food Additives Code” include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid, natural additives such as subchromic pigment, licorice extract, crystalline cellulose, cold pigment, and guar gum, L - Examples include mixed preparations such as sodium glutamate preparations, noodle-added alkaline preparations, preservative preparations, and tar color preparations.
- the content of the active ingredients added to the food can be appropriately adjusted as needed, and is preferably added in an amount of 1 to 90 parts by weight per 100 parts by weight of the food. .
- Zebrafish larvae (Wild type, Brn3c:EGFP, etc.) were cultured in the breeding room of our research institute. Each larva was cultured in embryo medium (15mM NaCl, 0.5mM KCl, 1mM CaCl 2 , 1mM MgSO 4 , 0.15mM KH 2 PO 4 , 0.05mM NH 2 PO 4 and 0.7mM NaHCO 3 ).
- LC 50 Concentration (LC 50) and time of cisplatin that causes approximately 50% damage to hair cells in the lateral line of zebrafish by administering gentamicin, an ototoxic substance, to zebrafish about 5 days after fertilization. was calculated. Research results showed that 50% of hair cells were damaged when 50 ⁇ M gentamicin was administered for 1 hour, so this was selected. Accordingly, the effect was confirmed when 10 ⁇ M, 100 ⁇ M, 500 ⁇ M, and 1000 ⁇ M of ammonium lactate were simultaneously administered to 50 ⁇ M of gentamicin for 1 hour.
- the locations of hair cells in zebrafish are four locations: the orbit (SO1 and SO2), the ear (O1), and the larynx (OC1), and the number of hair cells was analyzed through a microscope (fluorescence microscope, confocal microscope, etc.).
- Candidate substances that can inhibit hair cell damage caused by gentamicin were administered to zebrafish larvae at different concentrations and their effects were compared and analyzed.
- ammonium lactate and gentamicin were administered together to zebrafish and the survival rates of hair cells were compared with the control group.
- the number of hair cells in the untreated control group was 53, and in the control group where only 50 ⁇ M gentamicin was administered without ammonium lactate, the number of hair cells was 26, and the survival rate was 50. % decreased, but it was confirmed that the survival rate of hair cells increased in a concentration-dependent manner in the group administered ammonium lactate at 10 ⁇ M, 100 ⁇ M, 500 ⁇ M, and 1000 ⁇ M together with gentamicin 50 ⁇ M.
- the survival rate increased by about 10% to 28 and 29 hair cells, while in the case of ammonium lactate 1000 ⁇ M, the survival rate increased by more than 60% with a total of 42 hair cells.
- ammonium lactate has a protective effect on hair cells.
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- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
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- General Chemical & Material Sciences (AREA)
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- Nutrition Science (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract
본 발명은 암모늄 락테이트를 유효성분으로 포함하는 난청 예방 또는 치료용 약학 조성물에 관한 것으로서, 젠타마이신에 의해 손상된 유모세포에 암모늄 락테이트를 처리하여 정상 유모세포의 개수가 증가함을 확인하여, 암모늄 락테이트를 유효성분으로 포함하는 약학조성물은 항생제인 암모늄 락테이트를 사용함에 따른 부작용 난청을 예방 또는 치료하는데 활용될 수 있다.
Description
본 발명은 암모늄 락테이트를 유효성분으로 포함하는 난청 예방 또는 치료용 약학 조성물을 제공한다.
젠타마이신(gentamycin)은 오랫동안 우수한 항생제로 널리 사용되며 미국식품의약청(Food and Drug Administration)으로부터 허가를 받은 약물이다. 미크로모노스포라 푸르프레아(micromonospora purprea) 및 미크로모노스포라 에키노스포라(micromonospora echinospora)가 생산하는 아미노 글루코시드 계열의 항생물질로, 젠타마이신 C1, C2, C1a의 혼합물이다. 그람양성균 중 포도상구균과 그람음성균 중 대장균 살모넬라균 및 변형균 녹농균 등에 효과가 있다. 젠타마이신은 페니실린이나 앰피실린(ampicillin)과 함께 장내구균성 심내막염의 치료에도 사용된다. 비경구적인 방법으로 투여하거나 외용제로 많이 사용된다.
최근 연구 발표에 의하면 젠타마이신은 항생제 투여를 통하여 약효를 볼 수 있는 뒤센형 근위축증의 진전을 완전히 차단할 수 있다고 한다. 다만, 부작용으로 영구적인 청각 상실과 신장 손상 등이 대표적인 것으로 알려져 있다.
이독성 난청은 이독성 약물의 사용으로 인해 발생하는 부작용으로서, 아미노글리코사이드(aminoglycoside) 항생제 및 일부 항암제 등이 이독성을 유발하는 것으로 알려져 있다. 아미노글리코사이드 항생제는 박테리아 30s 리보솜 서브유닛에 결합하여 단백 합성을 억제함으로써 항균작용을 나타내며, 이러한 아미노글리코사이드 항생제가 와우각 세포(cochlear cell)에 지속적으로 노출되면 코르티(corti) 기관의 외유모세포(outer hair cell)와 유모세포(sensory hair cell)가 사멸(apoptosis)하게 된다. 사멸 기전은 아미노글리코사이드 항생제와 Ca++ 복합체가 형성하는 반응성 활성 산소종(ROS)에 의한 것으로 알려져 있다.
현재까지 개발되어 임상시험이 진행 중인 이독성 난청 보호 약물 대부분은 활성산소 차단을 기전으로 하고 있다. 활성산소 차단 기전의 약물은 강력한 친핵체를 가지고 있어 항생제와 착화합물을 형성하여 활성산소의 생성을 억제하는 효능을 가지고 있으나 항생제 효과 또한 이로 인하여 저하되며, 비특이적 기작으로 인하여 그 효과가 미미하다는 근본적 한계를 가지고 있다.
따라서, 항생제의 효과가 저해되지 않고 이독성 난청에 대한 치료 효과가 있는 치료제의 개발이 필요한 실정이다.
본 발명의 목적은 암모늄 락테이트(ammonium lactate)를 유효성분으로 포함하는 난청 예방 또는 치료용 약학 조성물을 제공하는 데에 있다.
본 발명의 또 다른 목적은 암모늄 락테이트(ammonium lactate)를 유효성분으로 포함하는 난청 예방 또는 개선용 건강기능식품 조성물을 제공하는 데에 있다.
상기 목적을 달성하기 위하여, 본 발명은 암모늄 락테이트(ammonium lactate)를 유효성분으로 포함하는 난청 예방 또는 치료용 약학 조성물을 제공한다.
또한, 본 발명은 암모늄 락테이트(ammonium lactate)를 유효성분으로 포함하는 난청 예방 또는 개선용 건강기능식품 조성물을 제공한다.
암모늄 락테이트를 유효성분으로 포함하는 난청 예방 또는 치료용 약학 조성물에 관한 것으로서, 젠타마이신에 의해 손상된 유모세포에 암모늄 락테이트를 처리하여 정상 유모세포의 개수가 증가함을 확인하여, 암모늄 락테이트를 유효성분으로 포함하는 약학조성물은 항생제인 암모늄 락테이트를 사용함에 따른 부작용 난청을 예방 또는 치료하는데 활용될 수 있다.
도 1은 암모늄 락테이트(ammonium lactate)의 분자구조를 나타낸 것이다.
도 2는 암모늄 락테이트(ammonium lactate) 투여에 따른 제브라피쉬의 유모세포의 개수를 확인한 결과이다.
도 3은 암모늄 락테이트(ammonium lactate) 투여에 따른 제브라피쉬의 유모세포의 생존율을 확인할 결과이다.
이하, 본 발명을 보다 상세하게 설명한다.
본 발명은 암모늄 락테이트(ammonium lactate)를 유효성분으로 포함하는 난청 예방 또는 치료용 약학 조성물을 제공한다.
상기 난청은 이독성 난청, 돌발성 난청, 소음성 난청 및 노화성 난청으로 이루어진 군에서 하나 이상일 수 있다.
상기 이독성 난청은 항암제 또는 아미노글루코시드계 항생제에 의한 난청일 수 있다.
상기 항암제는 시스플라틴(cisplatin) 또는 카르보플라틴(carboplatin)일 수 있다.
상기 아미노글루코시드계 항생제는 아미카신(amikacin), 아르베카신(arbekacin), 카나마이신(kanamycin), 젠타마이신(gentamicin), 네오마이신(neomycin), 네틸마이신(netilmicin), 디베카신(dibekacin), 시소마이신(sisomycin), 스트렙토마이신(streptomycin), 토브라마이신(tobramycin), 리보도마이신(livodomycin) 및 파로모마이신(paromomycin)으로 이루어진 군에서 선택될 수 있다.
본 발명의 다른 구체예에서, 약학 조성물은 약학 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제, 붕해제, 감미제, 피복제, 팽창제, 윤활제, 활택제, 향미제, 항산화제, 완충액, 정균제, 희석제, 분산제, 계면활성제, 결합제 및 윤활제로 이루어진 군에서 선택되는 하나 이상의 첨가제를 추가로 포함할 수 있다. 구체적으로 담체, 부형제 및 희석제는 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 광물유를 사용할 수 있으며, 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 조성물에 적어도 하나 이상의 부형제, 예를 들면, 전분, 칼슘카보네이트, 수크로스 또는 락토오스, 젤라틴 등을 섞어 조제할 수 있다. 또한 단순한 부형제 이외에 마그네슘 스티레이트, 탈크 같은 윤활제들도 사용할 수 있다. 경구를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 있으며 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제 등이 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기재로는 위텝솔 (witepsol), 마크로골, 트윈 (tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. 본 발명의 일실시예에 따르면, 상기 약학 조성물은 정맥내, 동맥내, 복강내, 근육내, 동맥내, 복강내, 흉골내, 경피, 비측내, 흡입, 국소, 직장, 경구, 안구내 또는 피내 경로를 통해 통상적인 방식으로 대상체로 투여할 수 있다. 본 발명에 따른 유효성분의 투여량은 대상체의 상태 및 체중, 질환의 종류 및 정도, 약물 형태, 투여경로 및 기간에 따라 달라질 수 있으며 당업자에 의해 적절하게 선택될 수 있고, 1일 투여량이 0.01 mg/kg 내지 200 mg/kg, 바람직하게는 0.1 mg/kg 내지 200 mg/kg, 보다 바람직하게는 0.1 mg/kg 내지 100 mg/kg 일 수 있다. 투여는 하루에 한번 투여할 수도 있고 수회로 나누어 투여할 수도 있으며, 이에 의해 본 발명의 범위가 제한되는 것은 아니다.
또한, 본 발명은 암모늄 락테이트(ammonium lactate)를 유효성분으로 포함하는 난청 예방 또는 개선용 건강기능식품 조성물을 제공한다.
상기 건강기능식품은 여러 가지 영양제, 비타민, 광물 (전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제 (치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 천연 과일 주스, 합성 과일 주스 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 또한, 건강기능식품 조성물은 육류, 소세지, 빵, 초콜릿, 캔디류, 스넥류, 과자류, 피자, 라면, 껌류, 아이스크림류, 스프, 음료수, 차, 기능수, 드링크제, 알코올 및 비타민 복합제 중 어느 하나의 형태일 수 있다. 또한, 상기 건강기능식품은 식품첨가물을 추가로 포함할 수 있으며, "식품첨가물"로서의 적합 여부는 다른 규정이 없는 한 식품의약품안전청에 승인된 식품첨가물공전의 총칙 및 일반 시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다. 상기 "식품첨가물공전"에 수재된 품목으로 예를 들어, 케톤류, 글리신, 구연산칼륨, 니코틴산, 계피산 등의 화학적 합성품, 감색소, 감초추출물, 결정셀룰로오스, 고랭색소, 구아검 등의 천연첨가물, L-글루타민산나트륨 제제, 면류 첨가 알칼리제, 보존료제제, 타르색소 제제 등의 혼합 제제류 등을 들 수 있다. 이때, 건강기능식품을 제조하는 과정에서 식품에 첨가되는 유효성분은 필요에 따라 그 함량을 적절히 가감할 수 있으며, 바람직하게는 식품 100 중량부에 1 중량부 내지 90 중량부 포함되도록 첨가될 수 있다.
이하, 본 발명의 이해를 돕기 위하여 실시예 등을 들어 상세하게 설명하기로 한다. 다만 하기의 실시예 등은 본 발명의 내용을 예시하는 것일 뿐 본 발명의 범위가 하기 실시예 등에 한정되는 것은 아니다. 본 발명의 실시예 등은 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.
<실험 예 1> 제브라피쉬 사육
제브라피쉬 유생(Wild type, Brn3c:EGFP 등)을 본 연구기관의 사육실에서 배양하였다. 각각의 유생은 embryo 배지에서 배양(15mM NaCl, 0.5mM KCl, 1mM CaCl2, 1mM MgSO4, 0.15mM KH2PO4, 0.05mM NH2PO4 및 0.7mM NaHCO3)하였다.
<실험 예 2> 제브라피쉬의 유모세포(hair cell) 분석
수정 후 5일경 된 제브라피쉬에 이독성 유발물질인 젠타마이신을 투여하여 제브라피쉬의 측선(lateral line)의 유모세포(hair cell)의 손상을 50% 정도 유발하는 시스플라틴의 농도(LC 50)와 시간을 산정하였다. 연구 결과에서 젠타마이신 50μM, 1시간 투여시에 유모세포의 50% 정도가 손상되어 이를 선택하였다. 이에 암모늄 락테이트을 10μM, 100μM, 500μM 및 1000μM을 젠타마이신 50μM에 1시간 동시에 투여하였을시에 그 효과를 확인할 수 있었다.
제브라피쉬의 유모세포의 위치는 안와(SO1 and SO2), 귀(O1) 및 후두(OC1)의 4곳으로, 유모세포의 개수를 현미경(형광현미경, Confocal 현미경 등)을 통하여 분석하였다. 젠타마이신에 의한 유모세포의 손상을 억제할 수 있는 후보물질을 농도를 달리하여 제브라피쉬 유생에 투여하여 그 효과를 비교 분석하였다.
<실시 예 1> 암모늄 락테이트의 제브라피쉬 유모세포 보호 효과 검증
암모늄 락테이트의 제브라피쉬 유모세포 보호 효과를 검증하기 위해 제브라피쉬에 암모늄 락테이트와 젠타마이신을 함께 투여하여 대조군과 유모세포의 생존율을 비교하였다.
그 결과, 도 2 및 도 3에 따르면, 아무것도 처리하지 않은 대조군의 유모세포의 수는 53개였으며, 암모늄 락테이트를 투여하지 않고 젠타마이신만 50μM 투여한 대조군의 경우 유모세포가 26개로 생존율이 50% 감소하였으나, 이후 암모늄 락테이트를 10μM, 100μM, 500μM 및 1000μM을 젠타마이신 50μM과 함께 투여한 군에서는 농도의존적으로 유모세포의 생존율이 증가함을 확인할 수 있었다. 특히, 암모늄 락테이트 100μM 및 500μM의 경우 유모세포가 28개 및 29개로 생존율이 약 10% 증가한 반면, 암모늄 락테이트 1000μM의 경우 유모세포가 총 42개로 생존율이 60% 이상 증가함을 확인하였다.
따라서, 암모늄 락테이트가 유모세포의 보호 효과가 있음을 확인할 수 있었다.
전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술 분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다.
본 발명의 범위는 후술하는 청구범위에 의하여 나타내어지며, 청구범위의 의미 및 범위 그리고 그 균등 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.
Claims (6)
- 암모늄 락테이트(ammonium lactate)를 유효성분으로 포함하는 난청 예방 또는 치료용 약학 조성물.
- 청구항 1에 있어서,상기 난청은 이독성 난청, 돌발성 난청, 소음성 난청 및 노화성 난청으로 이루어진 군에서 하나 이상인 것을 특징으로 하는 약학 조성물.
- 청구항 2에 있어서,상기 이독성 난청은 항암제 또는 아미노글루코시드계 항생제에 의한 난청인 것을 특징으로 하는 약학 조성물.
- 청구항 3에 있어서,상기 항암제는 시스플라틴(cisplatin) 또는 카르보플라틴(carboplatin)인 것을 특징으로 하는 약학 조성물.
- 청구항 3에 있어서,상기 아미노글루코시드계 항생제는 아미카신(amikacin), 아르베카신(arbekacin), 카나마이신(kanamycin), 젠타마이신(gentamicin), 네오마이신(neomycin), 네틸마이신(netilmicin), 디베카신(dibekacin), 시소마이신(sisomycin), 스트렙토마이신(streptomycin), 토브라마이신(tobramycin), 리보도마이신(livodomycin) 및 파로모마이신(paromomycin)으로 이루어진 군에서 선택되는 하나 이상인 것을 특징으로 하는 약학조성물.
- 암모늄 락테이트(ammonium lactate)를 유효성분으로 포함하는 난청 예방 또는 개선용 건강기능식품 조성물.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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KR10-2022-0140306 | 2022-10-27 | ||
KR1020220140306A KR20240059256A (ko) | 2022-10-27 | 2022-10-27 | 암모늄 락테이트를 유효성분으로 포함하는 난청 예방 또는 치료용 약학 조성물 |
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6012112B2 (ja) * | 2011-02-18 | 2016-10-25 | オトノミ—,インク. | 薬物により誘発される耳毒性の予防又は回復 |
KR20180003530A (ko) * | 2015-02-06 | 2018-01-09 | 유니버시티 오브 워싱톤 | 감각 유모 세포 사멸을 예방 또는 치료하기 위한 화합물 및 방법 |
KR102003609B1 (ko) * | 2017-11-14 | 2019-07-24 | 연세대학교 원주산학협력단 | 난청 진단을 위한 miR-205 및 이의 용도 |
KR20200018041A (ko) * | 2018-08-10 | 2020-02-19 | 아주대학교산학협력단 | 포스콜린 및 레티노산을 유효성분으로 포함하는 감각신경성 난청의 예방 또는 치료용 약학 조성물 |
KR102441661B1 (ko) * | 2020-07-27 | 2022-09-13 | 연세대학교 원주산학협력단 | 중간엽줄기세포 유래 엑소좀을 유효성분으로 포함하는 난청 예방용 조성물 |
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2022
- 2022-10-27 KR KR1020220140306A patent/KR20240059256A/ko unknown
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2023
- 2023-10-26 WO PCT/KR2023/016730 patent/WO2024091014A1/ko unknown
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6012112B2 (ja) * | 2011-02-18 | 2016-10-25 | オトノミ—,インク. | 薬物により誘発される耳毒性の予防又は回復 |
KR20180003530A (ko) * | 2015-02-06 | 2018-01-09 | 유니버시티 오브 워싱톤 | 감각 유모 세포 사멸을 예방 또는 치료하기 위한 화합물 및 방법 |
KR102003609B1 (ko) * | 2017-11-14 | 2019-07-24 | 연세대학교 원주산학협력단 | 난청 진단을 위한 miR-205 및 이의 용도 |
KR20200018041A (ko) * | 2018-08-10 | 2020-02-19 | 아주대학교산학협력단 | 포스콜린 및 레티노산을 유효성분으로 포함하는 감각신경성 난청의 예방 또는 치료용 약학 조성물 |
KR102441661B1 (ko) * | 2020-07-27 | 2022-09-13 | 연세대학교 원주산학협력단 | 중간엽줄기세포 유래 엑소좀을 유효성분으로 포함하는 난청 예방용 조성물 |
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