KR20230032526A - Composition for inhibiting eye damage - Google Patents
Composition for inhibiting eye damage Download PDFInfo
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- KR20230032526A KR20230032526A KR1020210115467A KR20210115467A KR20230032526A KR 20230032526 A KR20230032526 A KR 20230032526A KR 1020210115467 A KR1020210115467 A KR 1020210115467A KR 20210115467 A KR20210115467 A KR 20210115467A KR 20230032526 A KR20230032526 A KR 20230032526A
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- primary cilia
- eye
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Abstract
Description
본 명세서는 눈 손상 억제용 조성물에 관한 것이다.The present specification relates to a composition for inhibiting eye damage.
눈은 빛에 반응하여 시각 정보를 만드는 감각 기관이다. 눈은 둥근 공 모양으로 세 개의 막으로 둘러싸인 내부 공간으로 이루어진다. 가장 바깥에 있는 막은 투명한 각막(cornea)과 불투명한 공막(sclera)이다. 중간에 있는 맥락막(choroid)은 양분을 공급하는 혈관이 지나간다. 가장 안쪽에 있는 막은 망막(retina)이다. 섬모체(ciliary body)와 홍채(iris)는 망막과 이어져있는 섬모 상피와 홍채 상피로 덮여있다.The eye is a sensory organ that produces visual information in response to light. The eye is a round ball with an interior space surrounded by three membranes. The outermost membrane is the transparent cornea and the opaque sclera. The choroid, in the middle, carries blood vessels that supply nutrients. The innermost membrane is the retina. The ciliary body and the iris are covered with the ciliary epithelium and the iris epithelium, which are connected to the retina.
자외선, 미세먼지와 같은 자극으로 눈, 특히, 망막세포에 손상이 가해질 경우 망막색소변성증, 노인성 황반변성, 당뇨망막병증 등의 질병이 유발되는 것으로 알려져 있으나, 이를 조절할 수 있는 해결책은 거의 없는 실정이다.It is known that diseases such as retinitis pigmentosa, age-related macular degeneration, and diabetic retinopathy are induced when damage to the eyes, especially retinal cells, is caused by stimuli such as ultraviolet rays and fine dust, but there are few solutions to control them. .
일차 섬모(primary cilia)는 바이오 안테나로써 세포가 주변 환경의 변화에 맞게 행동하는데 중요한 역할을 하는 세포 구조체이다. 망막세포에서 이러한 일차 섬모가 활성화 되면 망막의 발달을 활발히 하고, 간상세포와 원추세포를 보호하는 등 눈에 바람직한 효과를 나타내는 것으로 알려져 있다.Primary cilia are cell structures that play an important role in helping cells behave in response to changes in the surrounding environment as bioantennas. When these primary cilia are activated in retinal cells, it is known to have desirable effects on the eyes, such as activating retinal development and protecting rod cells and cone cells.
본 발명자들은 2-이소프로필말산이 일차 섬모를 활성화하여 눈 손상을 억제하는 효과가 있음을 확인하고 본 발명을 완성하였다.The present inventors confirmed that 2-isopropylmalic acid has an effect of inhibiting eye damage by activating primary cilia and completed the present invention.
일 측면에서, 본 개시는 눈 손상 억제용 조성물을 제공하고자 한다.In one aspect, the present disclosure seeks to provide a composition for inhibiting eye damage.
일 측면에서, 본 개시는 2-이소프로필말산(2-isopropylmalic acid), 이의 염, 수화물 또는 용매화물을 유효성분으로 포함하는 눈 손상 억제용 조성물을 제공한다.In one aspect, the present disclosure provides a composition for inhibiting eye damage comprising 2-isopropylmalic acid, a salt, hydrate or solvate thereof as an active ingredient.
예시적인 일 구현예에서, 상기 2-이소프로필말산(2-isopropylmalic acid), 이의 염, 수화물 또는 용매화물 조성물은 1.7 내지 90 mg/kg/일의 투여량으로 투여될 수 있다.In an exemplary embodiment, the composition of 2-isopropylmalic acid, a salt, hydrate or solvate thereof may be administered at a dosage of 1.7 to 90 mg/kg/day.
예시적인 일 구현예에서, 상기 눈 손상은 망막세포의 손상일 수 있다.In one exemplary embodiment, the eye damage may be damage to retinal cells.
예시적인 일 구현예에서, 상기 망막세포는 망막색소상피세포를 포함할 수 있다.In an exemplary embodiment, the retinal cells may include retinal pigment epithelial cells.
예시적인 일 구현예에서, 상기 눈 손상은 미세먼지에 의한 것일 수 있다.In one exemplary embodiment, the eye damage may be caused by fine dust.
예시적인 일 구현예에서, 상기 조성물은 식품, 약학 또는 화장료 조성물일 수 있다.In an exemplary embodiment, the composition may be a food, pharmaceutical or cosmetic composition.
일 측면에서, 본 개시는 2-이소프로필말산(2-isopropylmalic acid), 이의 염, 수화물 또는 용매화물을 유효성분으로 포함하는 눈의 일차 섬모 활성화용 조성물을 제공한다. In one aspect, the present disclosure provides a composition for activating primary cilia of the eye comprising 2-isopropylmalic acid, a salt, hydrate or solvate thereof as an active ingredient.
예시적인 일 구현예에서, 상기 눈의 일차 섬모 활성화는 미세먼지에 의해 억제된 일차 섬모의 활성화일 수 있다. In an exemplary embodiment, the activation of primary cilia of the eye may be activation of primary cilia suppressed by fine dust.
예시적인 일 구현예에서, 상기 일차 섬모는 망막세포의 일차 섬모일 수 있다.In an exemplary embodiment, the primary cilia may be primary cilia of retinal cells.
예시적인 일 구현예에서, 상기 조성물은 식품 조성물, 화장료 조성물 또는 약학 조성물일 수 있다.In an exemplary embodiment, the composition may be a food composition, a cosmetic composition or a pharmaceutical composition.
일 측면에서, 본 개시에 의한 조성물은 부작용이 없으면서도 눈 손상을 억제하는 효과가 뛰어나다.In one aspect, the composition according to the present disclosure has an excellent effect of inhibiting eye damage without side effects.
일 측면에서, 본 개시에 의한 조성물은 눈의 염증을 완화하는 효과가 뛰어나다.In one aspect, the composition according to the present disclosure is excellent in relieving eye inflammation.
일 측면에서, 본 개시에 의한 조성물은 눈의 일차 섬모를 활성화할 수 있다.In one aspect, a composition according to the present disclosure is capable of activating the primary cilia of the eye.
도 1은 본 개시의 일 구현예에 따른 2-이소프로필말산의 세포 독성을 측정한 결과이다.
도 2는 본 개시의 일 구현예에 따른 2-이소프로필말산을 망막색소상피세포에 처리하고 현광현미경으로 관찰한 결과이다.
도 3은 본 개시의 일 구현예에 따른 2-이소프로필말산을 망막색소상피세포에 처리하고 일차 섬모의 생성 비율 및 일차 섬모의 길이를 측정하여 그 결과를 나타낸 그래프이다.
도 4는 본 개시의 일 구현예에 따른 2-이소프로필말산을 미세먼지에 노출된 망막색소상피세포에 처리하고 현광현미경으로 관찰한 결과이다.
도 5는 본 개시의 일 구현예에 따른 2-이소프로필말산을 미세먼지에 노출된 망막색소상피세포에 처리하고 일차 섬모의 생성 비율 및 일차 섬모의 길이를 측정하여 그 결과를 나타낸 그래프이다.
도 6은 본 개시의 일 구현예에 따른 2-이소프로필말산의 c-Jun 인산화 억제 효과를 측정한 결과이다.
도 7 및 8은 본 개시의 일 구현예에 따른 2-이소프로필말산의 세포내 활성산소종 억제 효과를 측정한 결과이다.
도 9은 본 개시의 일 구현예에 따른 2-이소프로필말산의 염증성 사이토카인 억제 효과를 측정한 결과이다.1 is a result of measuring the cytotoxicity of 2-isopropylmalic acid according to an embodiment of the present disclosure.
2 is a result of treating retinal pigment epithelial cells with 2-isopropylmalic acid according to an embodiment of the present disclosure and observing them under a flashlight microscope.
3 is a graph showing the results obtained by treating retinal pigment epithelial cells with 2-isopropylmalic acid according to an embodiment of the present disclosure and measuring the primary cilia generation rate and primary cilia length.
4 is a result of treating retinal pigment epithelial cells exposed to fine dust with 2-isopropylmalic acid according to an embodiment of the present disclosure and observing them under a flashlight microscope.
5 is a graph showing the results obtained by treating retinal pigment epithelial cells exposed to fine dust with 2-isopropylmalic acid according to an embodiment of the present disclosure, and measuring the primary cilia generation rate and primary cilia length.
6 is a result of measuring the c-Jun phosphorylation inhibitory effect of 2-isopropylmalic acid according to an embodiment of the present disclosure.
7 and 8 are results of measuring the intracellular reactive oxygen species inhibitory effect of 2-isopropylmalic acid according to one embodiment of the present disclosure.
9 is a result of measuring the inflammatory cytokine inhibitory effect of 2-isopropylmalic acid according to one embodiment of the present disclosure.
이하 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
일 측면에서, 본 개시는 2-이소프로필말산(2-isopropylmalic acid), 이의 염, 수화물 또는 용매화물을 유효성분으로 포함하는 눈 손상 억제용 조성물을 제공한다.In one aspect, the present disclosure provides a composition for inhibiting eye damage comprising 2-isopropylmalic acid, a salt, hydrate or solvate thereof as an active ingredient.
본 명세서에서, 2-이소프로필말산(2-isopropylmalic acid)은 하기의 화학식 1로 표현될 수 있다.In the present specification, 2-isopropylmalic acid may be represented by
[화학식 1][Formula 1]
본 명세서에서 "염"은 의약, 화장품 및 식품에서 허용 가능하고 모 화합물(parent compound)의 바람직한 활성을 갖는 본 발명의 일 측면에 따른 염을 의미한다. 상기 염은 (1) 염산, 브롬화수소산, 황산, 질산, 인산 등과 같은 무기산으로 형성되거나; 또는 아세트산, 프로파이온산, 헥사노산, 시클로펜테인프로피온산, 글라이콜산, 피루브산, 락트산, 말론산, 숙신산, 말산, 말레산, 푸마르산, 타르타르산, 시트르산, 벤조산, 3-(4-히드록시벤조일) 벤조산, 신남산, 만델산, 메테인설폰산, 에테인설폰산, 1,2-에테인-디설폰산, 2-히드록시에테인설폰산, 벤젠설폰산, 4-클로로벤젠설폰산, 2-나프탈렌설폰산, 4-톨루엔설폰산, 캄퍼설폰산, 4-메틸바이시클로 [2,2,2]-oct-2-엔-1-카르복실산, 글루코헵톤산, 3-페닐프로파이온산, 트리메틸아세트산, tert-부틸아세트산, 라우릴 황산, 글루콘산, 글루탐산, 히드록시나프토산, 살리실산, 스테아르산, 뮤콘산과 같은 유기산으로 형성되는 산 부가염(acid addition salt); 또는 (2) 모 화합물에 존재하는 산성 프로톤이 치환될 때 형성되는 염을 포함할 수 있다. 또한, 상기 염은 약학적으로 허용 가능한 염일 수 있다.As used herein, "salt" means a salt according to one aspect of the present invention that is acceptable in medicine, cosmetics, and food and has the desired activity of the parent compound. These salts are (1) formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like; or acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl) Benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-Toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo[2,2,2]-oct-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert - acid addition salts formed with organic acids such as butylacetic acid, laurylsulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, and muconic acid; or (2) a salt formed when an acidic proton present in the parent compound is substituted. In addition, the salt may be a pharmaceutically acceptable salt.
본 명세서에서 "약학적으로 허용 가능"이란 통상의 의약적 복용량(medicinal dosage)으로 이용할 때 상당한 독성 효과를 피함으로써, 동물, 더 구체적으로는 인간에게 사용할 수 있다는 정부 또는 이에 준하는 규제 기구의 승인을 받을 수 있거나 승인 받거나, 또는 약전에 열거되거나 기타 일반적인 약전으로 인지되는 것을 의미한다.As used herein, “pharmaceutically acceptable” means approval by the government or a regulatory body equivalent thereto that can be used in animals, more specifically in humans, by avoiding significant toxic effects when used in normal medical dosages. Received or approved, or listed in a pharmacopeia or otherwise recognized in a general pharmacopeia.
본 명세서에서 "수화물(hydrate)"은 물이 결합되어 있는 화합물을 의미하며, 물과 화합물 사이에 화학적인 결합력이 없는 내포 화합물을 포함하는 광범위한 개념이다.In the present specification, "hydrate" means a compound in which water is bound, and is a broad concept including an inclusion compound having no chemical bonding force between water and the compound.
본 명세서에서 "용매화물"은 용질의 분자나 이온과 용매의 분자나 이온 사이에 생긴 고차의 화합물을 의미한다.As used herein, "solvate" refers to a higher order compound formed between solute molecules or ions and solvent molecules or ions.
본 명세서에서 "유효성분"은 단독으로 목적하는 활성을 나타내거나 또는 그 자체 활성이 없는 담체와 함께 활성을 나타낼 수 있는 성분을 의미한다.In the present specification, "active ingredient" means a component that exhibits the desired activity alone or that can exhibit activity together with a carrier that has no activity by itself.
일 구현예에 있어서, 상기 조성물의 투여에 의한 2-이소프로필말산, 이의 염, 수화물 또는 용매화물은 1.7 내지 90 mg/kg/일의 투여량으로 투여될 수 있다. 상기 조성물의 투여에 의한 2-이소프로필말산, 이의 염, 수화물 또는 용매화물의 투여량이 1.7 mg/kg/일 미만인 경우 눈 손상을 억제하는 효과를 나타내기 힘들 수 있으며, 90 mg/kg/일 초과인 경우 자극을 줄 수 있다. 구체적으로, 상기 조성물의 투여에 의한 2-이소프로필말산, 이의 염, 수화물 또는 용매화물의 투여량은 1.7 mg/kg/일 이상, 2 mg/kg/일 이상, 2.5 mg/kg/일 이상, 3 mg/kg/일 이상, 3.5 mg/kg/일 이상, 4 mg/kg/일 이상, 4.5 mg/kg/일 이상, 5 mg/kg/일 이상, 5.5 mg/kg/일 이상, 6 mg/kg/일 이상, 6.5 mg/kg/일 이상, 7 mg/kg/일 이상, 7.5 mg/kg/일 이상, 8 mg/kg/일 이상, 8.5 mg/kg/일 이상, 9 mg/kg/일 이상, 9.5 mg/kg/일 이상, 10 mg/kg/일 이상, 10.5 mg/kg/일 이상, 11 mg/kg/일 이상, 11.5 mg/kg/일 이상, 12 mg/kg/일 이상, 12.5 mg/kg/일 이상, 13 mg/kg/일 이상, 14 mg/kg/일 이상, 15 mg/kg/일 이상, 16 mg/kg/일 이상, 17 mg/kg/일 이상, 18 mg/kg/일 이상, 19 mg/kg/일 이상, 20 mg/kg/일 이상, 21 mg/kg/일 이상, 22 mg/kg/일 이상, 23 mg/kg/일 이상, 24 mg/kg/일 이상 또는 25 mg/kg/일 이상이면서, 90 mg/kg/일 이하, 89 mg/kg/일 이하, 88 mg/kg/일 이하, 87 mg/kg/일 이하, 86 mg/kg/일 이하, 85 mg/kg/일 이하, 84 mg/kg/일 이하, 83 mg/kg/일 이하, 82 mg/kg/일 이하, 81 mg/kg/일 이하, 80 mg/kg/일 이하, 79 mg/kg/일 이하, 78 mg/kg/일 이하, 77 mg/kg/일 이하, 76 mg/kg/일 이하, 75 mg/kg/일 이하, 74 mg/kg/일 이하, 73 mg/kg/일 이하, 72 mg/kg/일 이하, 71 mg/kg/일 이하, 70 mg/kg/일 이하, 69 mg/kg/일 이하, 68 mg/kg/일 이하, 67 mg/kg/일 이하, 66 mg/kg/일 이하 또는 65 mg/kg/일 이하일 수 있다.In one embodiment, 2-isopropylmalic acid, a salt, hydrate or solvate thereof by administration of the composition may be administered at a dosage of 1.7 to 90 mg/kg/day. When the dosage of 2-isopropylmalic acid, its salt, hydrate or solvate by administration of the composition is less than 1.7 mg/kg/day, it may be difficult to show the effect of inhibiting eye damage, and it is more than 90 mg/kg/day If it is, it can stimulate. Specifically, the dosage of 2-isopropylmalic acid, its salt, hydrate or solvate by administration of the composition is 1.7 mg/kg/day or more, 2 mg/kg/day or more, 2.5 mg/kg/day or more, 3 mg/kg/day or more, 3.5 mg/kg/day or more, 4 mg/kg/day or more, 4.5 mg/kg/day or more, 5 mg/kg/day or more, 5.5 mg/kg/day or more, 6 mg /kg/day or more, 6.5 mg/kg/day or more, 7 mg/kg/day or more, 7.5 mg/kg/day or more, 8 mg/kg/day or more, 8.5 mg/kg/day or more, 9 mg/kg /day or more, 9.5 mg/kg/day or more, 10 mg/kg/day or more, 10.5 mg/kg/day or more, 11 mg/kg/day or more, 11.5 mg/kg/day or more, 12 mg/kg/day 12.5 mg/kg/day or more, 13 mg/kg/day or more, 14 mg/kg/day or more, 15 mg/kg/day or more, 16 mg/kg/day or more, 17 mg/kg/day or more; 18 mg/kg/day or more, 19 mg/kg/day or more, 20 mg/kg/day or more, 21 mg/kg/day or more, 22 mg/kg/day or more, 23 mg/kg/day or more, 24 mg /kg/day or more or 25 mg/kg/day or more, but less than or equal to 90 mg/kg/day, less than or equal to 89 mg/kg/day, less than or equal to 88 mg/kg/day, less than or equal to 87 mg/kg/day, or less than or equal to 86 mg/kg/day kg/day or less, 85 mg/kg/day or less, 84 mg/kg/day or less, 83 mg/kg/day or less, 82 mg/kg/day or less, 81 mg/kg/day or less, 80 mg/kg/day or less days or less, 79 mg/kg/day or less, 78 mg/kg/day or less, 77 mg/kg/day or less, 76 mg/kg/day or less, 75 mg/kg/day or less, 74 mg/kg/day or less , 73 mg/kg/day or less, 72 mg/kg/day or less, 71 mg/kg/day or less, 70 mg/kg/day or less, 69 mg/kg/day or less, 68 mg/kg/day or less, 67 Not more than mg/kg/day, not more than 66 mg/kg/day or not more than 65 mg/kg/day can
일 구현예에 있어서, 상기 눈 손상은 망막세포의 손상일 수 있다. 상기 망막세포는 망막색소상피세포를 포함할 수 있다.In one embodiment, the eye damage may be damage to retinal cells. The retinal cells may include retinal pigment epithelial cells.
일 구현예에 있어서, 상기 눈 손상은 미세먼지에 의한 것일 수 있다.In one embodiment, the eye damage may be caused by fine dust.
일 구현예에 있어서, 상기 눈 손상 억제는 눈 염증 완화를 포함할 수 있다.In one embodiment, inhibiting eye damage may include relieving eye inflammation.
일 구현예에 있어서, 상기 조성물은 일차 섬모를 활성화할 수 있다. 본 명세서에서 일차 섬모를 활성화한다는 것은 세포에서 일차 섬모의 생성을 촉진하거나 일차 섬모의 길이를 증진시키는 것을 의미할 수 있다.In one embodiment, the composition is capable of activating primary cilia. In the present specification, activating primary cilia may mean promoting the production of primary cilia in a cell or increasing the length of primary cilia.
본 명세서에서 "일차 섬모"는, 세포체에서 돌출된 소기관으로서, 화학적 자극, 물리적 자극, 빛, 삼투압, 유체 흐름, 및 중력 신호 등을 포함하는 다양한 외부자극을 감지하는 세포 소기관을 말한다. 눈의 일차 섬모의 활성이 억제되면 망막색소변성증, 노인성 황반변성, 당뇨망막병증, 염증성 안질환 등이 유발될 수 있다. In the present specification, "primary cilia" are organelles protruding from the cell body, which sense various external stimuli including chemical stimuli, physical stimuli, light, osmotic pressure, fluid flow, and gravitational signals. When the activity of primary cilia of the eye is inhibited, retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, inflammatory eye diseases, and the like can be induced.
일 구현예에 있어서, 상기 조성물은 미세먼지에 의해 억제된 눈의 일차 섬모의 생성을 증가시킬 수 있다.In one embodiment, the composition can increase the production of primary cilia of the eye, which is suppressed by fine dust.
본 명세서에서 "미세먼지"라 함은, 우리 눈에 보이지 않는 아주 작은 물질로 대기 중에 오랫동안 떠다니거나 흩날리는 입자상의 물질을 의미한다. 구체적으로, 상기 미세먼지의 입자 크기는 입경이 10μm 이하 (PM 10), 보다 구체적으로, 2.5μm 이하 (PM 2.5)일 수 있다. 특히 입경이 2.5μm 이하 (PM 2.5)인 입자상의 물질은 "초미세먼지"라 하는데, 본 명세서에서 "미세먼지"는 "초미세먼지"도 포함하는 것으로 의도된다.In this specification, "fine dust" refers to particulate matter that floats or scatters in the air for a long time as a very small substance invisible to our eyes. Specifically, the particle size of the fine dust may have a particle diameter of 10 μm or less (PM 10), more specifically, 2.5 μm or less (PM 2.5). In particular, particulate matter having a particle diameter of 2.5 μm or less (PM 2.5) is referred to as “ultrafine dust”, and in this specification, “fine dust” is intended to include “ultrafine dust”.
일 구현예에 있어서, 상기 조성물은 화장료 조성물일 수 있다. 상기 화장료 조성물은, 예를 들어, 유연화장수, 수렴화장수, 영양화장수, 영양크림, 마사지크림, 아이크림, 아이에센스, 에센스, 클렌징크림, 클렌징로션, 클렌징폼, 클렌징워터, 팩, 파우더, 보디로션, 보디크림, 보디에센스, 보디세정제, 염모제, 샴푸, 린스, 정발제, 양모제, 연고, 젤, 크림, 패취, 분무제, 분말제 및 피부 접착타입 등의 제형을 가질 수 있으나 이에 한정되지는 않는다.In one embodiment, the composition may be a cosmetic composition. The cosmetic composition, for example, softening lotion, astringent lotion, nutrient lotion, nutrient cream, massage cream, eye cream, eye essence, essence, cleansing cream, cleansing lotion, cleansing foam, cleansing water, pack, powder, body lotion , Body cream, body essence, body cleanser, hair dye, shampoo, rinse, hair styling agent, hair growth agent, ointment, gel, cream, patch, spray, powder, and skin adhesive type, but may have formulations such as, but are not limited thereto.
또한, 각각의 제형에 있어서 상기한 필수성분 이외에 다른 성분들은 기타 외용제의 종류 또는 사용목적 등에 따라 당업자가 어려움 없이 적합하게 선정하여 배합할 수 있다.In addition, other ingredients in addition to the essential ingredients described above in each formulation can be appropriately selected and blended without difficulty by those skilled in the art according to the type or purpose of use of other external preparations.
상기 화장료 조성물은 국소 적용에 적합한 모든 제형으로 제공될 수 있다. 예를 들면, 용액, 수상에 유상을 분산시켜 얻은 에멀젼, 유상에 수상을 분산시켜 얻은 에멀젼, 현탁액, 고체, 겔, 분말, 페이스트, 마이크로 니들, 포말(foam) 또는 에어로졸 조성물의 제형으로 제공될 수 있다. 이러한 제형의 조성물은 당해 분야의 통상적인 방법에 따라 제조될 수 있다.The cosmetic composition may be provided in any formulation suitable for topical application. For example, it may be provided in the form of a solution, an emulsion obtained by dispersing an oil phase in an aqueous phase, an emulsion obtained by dispersing an aqueous phase in an oil phase, a suspension, a solid, a gel, a powder, a paste, a microneedle, a foam, or an aerosol composition. there is. Compositions of such formulations may be prepared according to conventional methods in the art.
본 명세서에 따른 화장료 조성물에는 본 명세서의 화합물 이외에 기능성 첨가물 및 일반적인 화장료 조성물에 포함되는 성분이 추가로 포함될 수 있다. 상기 기능성 첨가물로는 수용성 비타민, 유용성 비타민, 고분자 펩티드, 고분자 다당, 스핑고 지질 및 해초 엑기스로 이루어진 군에서 선택된 성분을 포함할 수 있다. 본 명세서에 따른 화장료 조성물은 주 효과를 손상시키지 않는 범위 내에서, 바람직하게는 주 효과에 상승 효과를 줄 수 있는 다른 성분들을 포함할 수 있다. 또한 본 명세서에 따른 화장료 조성물은 보습제, 에몰리언트제, 계면 활성제, 자외선 흡수제, 방부제, 살균제, 산화 방지제, pH 조정제, 유기 및 무기안료, 향료, 냉감제 또는 제한제를 더 포함할 수 있다. 상기 성분의 배합량은 본 명세서의 목적 및 효과를 손상시키지 않는 범위내에서 당업자가 용이하게 선정 가능하며, 그 배합량은 조성물 전체 중량을 기준으로 0.001 내지 10 중량%, 구체적으로 0.01 내지 3 중량%일 수 있다.The cosmetic composition according to the present specification may further include functional additives and components included in general cosmetic compositions in addition to the compounds of the present specification. The functional additive may include a component selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high-molecular peptides, high-molecular polysaccharides, sphingolipids, and seaweed extracts. The cosmetic composition according to the present specification may include other components capable of giving a synergistic effect to the main effect within a range that does not impair the main effect. In addition, the cosmetic composition according to the present specification may further include a moisturizer, an emollient agent, a surfactant, a UV absorber, a preservative, a bactericide, an antioxidant, a pH adjuster, an organic and inorganic pigment, a fragrance, a cooling agent or an antiperspirant. The blending amount of the components can be easily selected by those skilled in the art within a range that does not impair the purpose and effect of the present specification, and the blending amount may be 0.001 to 10% by weight, specifically 0.01 to 3% by weight based on the total weight of the composition. there is.
일 구현예에 있어서, 상기 조성물은 식품 조성물일 수 있다. 상기 식품 조성물의 제형은 특별히 한정되지 않으나, 예를 들어, 정제, 과립제, 환제, 분말제, 드링크제와 같은 액제, 캐러멜, 겔, 바, 티백 등으로 제형화 될 수 있다. 각 제형의 식품 조성물은 유효 성분 이외에 해당 분야에서 통상적으로 사용되는 성분들을 제형 또는 사용 목적에 따라 당업자가 어려움 없이 적의 선정하여 배합할 수 있으며, 다른 원료와 동시에 적용할 경우 상승 효과가 일어날 수 있다.In one embodiment, the composition may be a food composition. The formulation of the food composition is not particularly limited, but may be formulated into, for example, tablets, granules, pills, powders, liquids such as drinks, caramels, gels, bars, tea bags, and the like. The food composition of each formulation can be selected and blended without difficulty by those skilled in the art according to the formulation or purpose of use other than the active ingredient, and synergistic effects can occur when applied simultaneously with other ingredients.
일 구현예에 따른 식품 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 증진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 포함할 수 있다. 또한, 일 구현예에 따른 식품 조성물들은 천연 과일 쥬스 및 과일 주스 음료 및 야채 음료의 제조를 위한 과육을 포함할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않으나 일 구현예에 따른 조성물 100 중량부 당 0 내지 약 50 중량부의 범위에서 포함되는 것이 일반적이다.The food composition according to one embodiment includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like. In addition, the food compositions according to one embodiment may include natural fruit juice, fruit juice beverages, and fruit flesh for preparing vegetable beverages. These components may be used independently or in combination. The ratio of these additives is not so critical, but is generally included in the range of 0 to about 50 parts by weight per 100 parts by weight of the composition according to one embodiment.
일 구현예에 있어서, 상기 조성물은 약학 조성물일 수 있다. 상기 약학 조성물은 망막색소변성증, 노인성 황반변성, 당뇨망막병증 또는 염증성 안질환의 예방 또는 치료용 조성물일 수 있다. 상기 약학 조성물은 경구, 비경구, 직장, 국소, 경피, 정맥 내, 근육 내, 복강 내, 피하 등으로 투여될 수 있다. 경구 투여를 위한 제형은 정제(錠劑), 환제(丸劑), 연질 및 경질 캅셀제, 과립제(顆粒劑), 산제, 세립제, 액제, 유탁제(乳濁濟) 또는 펠렛제일 수 있으나, 이에 제한되는 것은 아니다. 비경구 투여를 위한 제형은 용액제, 현탁제, 유액제, 겔, 주사제, 점적제, 좌제(坐劑), 패취 또는 분무제일 수 있으나, 이에 제한되는 것은 아니다. 상기 제형은 당해 분야의 통상적인 방법에 따라 용이하게 제조될 수 있으며, 계면활성제, 부형제, 수화제, 유화 촉진제, 현탁제, 삼투압 조절을 위한 염 또는 완충제, 착색제, 향신료, 안정화제, 방부제, 보존제 또는 기타 상용하는 보조제를 추가로 포함할 수 있다.In one embodiment, the composition may be a pharmaceutical composition. The pharmaceutical composition may be a composition for preventing or treating retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy or inflammatory eye disease. The pharmaceutical composition may be administered orally, parenterally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, or subcutaneously. Formulations for oral administration may be tablets, pills, soft and hard capsules, granules, powders, fine granules, solutions, emulsions, or pellets, but are limited thereto. It is not. Formulations for parenteral administration may be solutions, suspensions, emulsions, gels, injections, drops, suppositories, patches or sprays, but are not limited thereto. The formulation can be easily prepared according to a conventional method in the art, and includes surfactants, excipients, wetting agents, emulsification accelerators, suspending agents, salts or buffers for osmotic pressure control, coloring agents, spices, stabilizers, preservatives, preservatives, or Other commonly used adjuvants may be further included.
다른 측면에서, 본 개시는 2-이소프로필말산(2-isopropylmalic acid), 이의 염, 수화물 또는 용매화물을 유효성분으로 포함하는 눈의 일차 섬모 활성화용 조성물을 제공한다.In another aspect, the present disclosure provides a composition for activating primary cilia of the eye comprising 2-isopropylmalic acid, a salt, hydrate or solvate thereof as an active ingredient.
일 구현예에 있어서, 상기 눈의 일차 섬모 활성화는 미세먼지에 의해 억제된 일차 섬모의 활성화일 수 있다. 눈이 미세먼지에 노출되면 눈의 일차 섬모의 생성이 억제되고 길이가 감소하게 된다. 본 개시에 따른 조성물은 이와 같이 미세먼지에 의해 일차 섬모의 생성이 억제되는 것을 막아 눈의 일차 섬모의 생성을 증진시키고, 미세먼지에 노출된 눈의 일차 섬모의 길이를 증가시킨다.In one embodiment, the activation of primary cilia of the eye may be activation of primary cilia suppressed by fine dust. When the eye is exposed to fine dust, the production of primary cilia in the eye is suppressed and the length is reduced. The composition according to the present disclosure prevents the suppression of primary cilia by fine dust, enhances the production of primary cilia in the eye, and increases the length of primary cilia in the eye exposed to fine dust.
일 구현예에 있어서, 상기 눈의 일차 섬모는 망막세포의 일차 섬모일 수 있다.In one embodiment, the primary cilia of the eye may be primary cilia of retinal cells.
이하, 실시예 등을 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 예시하기 위한 것으로, 본 발명의 범위가 이들 실시예에 의해 제한되는 것으로 해석되지 않는 것은 당업계에서 통상의 지식을 가진 자에게 있어 자명할 것이다.Hereinafter, the present invention will be described in more detail through examples and the like. These examples are only for illustrating the present invention, and it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as being limited by these examples.
[실험예 1] 세포 독성 측정[Experimental Example 1] Measurement of cytotoxicity
FBS(fetal bovine serum)이 10% 들어간 DMEM(Dulbecco's Modified Eagle's medium)에 인간 망막색소상피세포(retinal pigmented epithelial (RPE) cell)를 넣고 37℃, 5% CO2 조건 하에서 배양하였다. 상기 배양된 망막색소상피세포에 2-이소프로필말산(2-isopropylmalic acid)을 농도별로 24시간 동안 처리하였다. CCK8 시약(Donjindo社, CK04)을 DMEM 배지에 1/10로 희석하여 3시간 동안 처리한 후 450nm에서 흡광도를 측정하고, 그 결과를 도 1에 나타내었다.Human retinal pigmented epithelial (RPE) cells were placed in Dulbecco's Modified Eagle's medium (DMEM) containing 10% fetal bovine serum (FBS) and cultured at 37°C under 5% CO 2 conditions. The cultured retinal pigment epithelial cells were treated with 2-isopropylmalic acid at each concentration for 24 hours. CCK8 reagent (Donjindo Co., CK04) was diluted 1/10 in DMEM medium, treated for 3 hours, and then absorbance was measured at 450 nm, and the results are shown in FIG. 1 .
[실험예 2] 일차 섬모 활성화 평가[Experimental Example 2] Primary cilia activation evaluation
2-이소프로필말산의 일차 섬모 활성화 효과를 확인하기 위해, 인간 텔로머레이즈-불멸화된(Human telomerase-immortalized) 망막색소상피세포(retinal pigmented epithelial (RPE) cell, ATCC 社)에 Smo-GFP plasmid (Addgene 社)를 형질전환하여 RPE/Smo-GFP를 준비하였다. RPE/Smo-GFP에 2-이소프로필말산(Sigma Aldrich 社)을 농도별로(20 μM, 100 μM) 24시간 처리한 후 공초점현미경 (LSM510; Carl Zeiss Microimaging Inc., Thornwood, NY)으로 일차 섬모 생성 비율과 일차 섬모의 길이를 측정하여 그 결과를 도 2 및 3에 나타내었다. 일차 섬모의 생성 비율은 전체 세포 수에서 일차 섬모를 가진 세포 수의 비율을 %로 나타냈으며, 일차 섬모의 길이는 현미경 상에서 관찰되는 모든 섬모의 실체 길이를 측정한 것이다. 양성 대조군으로는 일차 섬모 생성 촉진 물질인 SAG(SMO agonist, Calbiochem 社)를 사용하였다.To confirm the primary cilia activation effect of 2-isopropylmalic acid, human telomerase-immortalized retinal pigmented epithelial (RPE) cells (ATCC) were inoculated with Smo-GFP plasmid ( Addgene Co.) to prepare RPE/Smo-GFP. RPE/Smo-GFP was treated with 2-isopropylmalic acid (Sigma Aldrich) at different concentrations (20 μM, 100 μM) for 24 hours, and then primary cilia were observed under a confocal microscope (LSM510; Carl Zeiss Microimaging Inc., Thornwood, NY). The production rate and length of primary cilia were measured and the results are shown in FIGS. 2 and 3 . The production rate of primary cilia was expressed as a percentage of the number of cells having primary cilia in the total number of cells, and the length of primary cilia was a measure of the actual length of all cilia observed under a microscope. As a positive control, SAG (SMO agonist, Calbiochem Co.), a primary cilia production promoting substance, was used.
도 2의 흰색 화살표는 일차 섬모를 나타내는 것으로, 도 2 및 3에서 확인할 수 있듯이, 2-이소프로필말산(2-IMPA)이 처리되는 경우 대조군에 비해 통계적으로 유의미하게 일차 섬모를 가진 세포의 비율이 증가하고 섬모의 길이도 길어지는 것을 확인할 수 있었다.White arrows in FIG. 2 indicate primary cilia, and as can be seen in FIGS. 2 and 3, when 2-isopropylmalic acid (2-IMPA) was treated, the percentage of cells with primary cilia was statistically significant compared to the control group. It was confirmed that the length of the cilia was also increased.
[실험예 3] 미세먼지에 의해 억제된 일차 섬모의 활성화 평가[Experimental Example 3] Evaluation of activation of primary cilia suppressed by fine dust
실험예 2의 RPE/Smo-GFP에 미세먼지(PM2.5)를 처리하였다. 구체적으로, 미세먼지는 테프론 필터(Teflon filter, Zefluor, Pall Life Science, Ann Arbor, MI, USA)를 사용하여 공기 중(37.34°N, 127.27°E, 167 m above sea level)에 있는 것을 직접 포집하고 이것을 세포 배양 배지에 50 ug/ml 농도로 처리하였다. 그 후, 2-이소프로필말산 100 μM을 24시간 처리한 후 Smo-GFP의 형광을 형광현미경을 이용해 육안으로 관찰한 후 일차 섬모 생성 비율과 일차 섬모의 길이를 측정하여 그 결과를 도 4 및 5에 나타내었다. 일차 섬모의 생성 비율은 전체 세포 수에서 일차 섬모를 가진 세포 수의 비율을 %로 나타냈으며, 일차 섬모의 길이는 현미경 상에서 관찰되는 모든 섬모의 실체 길이를 측정한 것이다. 양성 대조군으로는 일차 섬모 생성 촉진 물질인 SAG(SMO agonist, Calbiochem 社)를 사용하였다.RPE/Smo-GFP of Experimental Example 2 was treated with fine dust (PM2.5). Specifically, fine dust is directly collected from the air (37.34°N, 127.27°E, 167 m above sea level) using a Teflon filter (Zefluor, Pall Life Science, Ann Arbor, MI, USA) And this was treated with a concentration of 50 ug / ml in the cell culture medium. Then, after treatment with 100 μM of 2-isopropylmalic acid for 24 hours, the fluorescence of Smo-GFP was observed with the naked eye using a fluorescence microscope, and then the primary cilia generation rate and the length of primary cilia were measured, and the results are shown in FIGS. 4 and 5 shown in The production rate of primary cilia was expressed as a percentage of the number of cells having primary cilia in the total number of cells, and the length of primary cilia was a measure of the actual length of all cilia observed under a microscope. As a positive control, SAG (SMO agonist, Calbiochem Co.), a primary cilia production promoting substance, was used.
도 4 및 5에서 확인할 수 있듯이, 미세먼지를 처리하게 되면 망막색소상피세포의 일차 섬모 생성이 억제되나, 2-이소프로필말산이 처리되는 경우 미세먼지에 의해 억제된 일차 섬모의 생성이 회복되고 일차 섬모의 길이도 길어지는 것을 확인할 수 있었다.As can be seen in FIGS. 4 and 5, when fine dust is treated, primary cilia production of retinal pigment epithelial cells is suppressed, but when 2-isopropylmalic acid is treated, the production of primary cilia suppressed by fine dust is restored and the primary cilia are suppressed. It was confirmed that the length of the cilia was also increased.
[실험예 4] 바이오 마커의 발현 변화 평가 [Experimental Example 4] Evaluation of biomarker expression change
c-Jun 인산화 평가Evaluation of c-Jun phosphorylation
실험예 2의 RPE/Smo-GFP에 미세먼지 (PM2.5)를 처리하였다. 그 후, 2-이소프로필말산 100 μM을 24시간 처리한 후 cell lysate를 만들고 단백질 정량을 하여 동량의 단백질을 전기영동으로 분리한 후 western blotting으로 c-Jun, p-c-Jun(인산화된 c-Jun)에 특이적인 항체를 사용하여 항원-항체 반응으로 각 단백질들의 발현을 측정하여 그 결과를 도 6에 나타내었다. RPE/Smo-GFP of Experimental Example 2 was treated with fine dust (PM2.5). Then, after treatment with 100 μM of 2-isopropylmalic acid for 24 hours, cell lysate was made, protein was quantified, and the same amount of protein was separated by electrophoresis, and then c-Jun, p-c-Jun (phosphorylated c-Jun ) The expression of each protein was measured by an antigen-antibody reaction using an antibody specific for ), and the results are shown in FIG. 6 .
도 6에서 확인할 수 있듯이, 미세먼지를 처리하게 되면 c-Jun의 인산화가 촉진되어 p-c-Jun의 양이 증가되지만, 2-이소프로필말산이 처리되는 경우 미세먼지에 의한 c-Jun의 인산화가 억제되는 것을 확인할 수 있었다. 이와 같은 효과는 c-Jun의 인산화를 억제한다고 알려진 물질인 SP600125(sigma aldrich 社)와 유사하였다. c-Jun의 인산화가 촉진되면 일차 섬모 생성이 억제되는데 2-이소프로필말산은 c-Jun의 인산화를 억제하여 일차 섬모를 활성화시키는 것을 알 수 있었다. As can be seen in FIG. 6, when fine dust is treated, phosphorylation of c-Jun is promoted and the amount of p-c-Jun is increased, but when 2-isopropylmalic acid is treated, phosphorylation of c-Jun by fine dust is inhibited. was able to confirm that This effect was similar to SP600125 (Sigma Aldrich), a substance known to inhibit c-Jun phosphorylation. When the phosphorylation of c-Jun is promoted, the production of primary cilia is inhibited. It was found that 2-isopropylmalic acid inhibits phosphorylation of c-Jun to activate primary cilia.
세포 내 활성산소종(ROS) 수준 평가Assessment of intracellular reactive oxygen species (ROS) levels
형광 염료인 2',7'-dichlorofluorescein diacetate (H2DCF-DA) (Invitrogen社)를 이용하여 세포 내 활성산소종(ROS) 수준을 측정하였다. H2DCF-DA는 활성산소에 의해 2',7'-dichlorofluorescein (DCF)로 산화되어 형광을 띄게 되는 물질이다. 실험예 2의 RPE/Smo-GFP에 미세먼지 (PM2.5)를 처리한 후, 2-이소프로필말산 100 μM을 24시간 처리하였다. 그 후, 무혈청 배지에서 H2DCF-DA(20 M)와 함께 40분동안 배양하여 형광 변화를 도 7에 나타내었으며, 대조군과 비교한 상대적인 비율을 도 8에 나타내었다. 비교군으로는 항산화제인 NAC(N-acetyl-cysteine)를 사용하였다.Intracellular reactive oxygen species (ROS) levels were measured using a fluorescent dye, 2',7'-dichlorofluorescein diacetate (H2DCF-DA) (Invitrogen). H2DCF-DA is a substance that becomes fluorescent by being oxidized to 2',7'-dichlorofluorescein (DCF) by active oxygen. After fine dust (PM2.5) was treated with RPE/Smo-GFP of Experimental Example 2, 100 μM of 2-isopropylmalic acid was treated for 24 hours. Thereafter, incubation with H2DCF-DA (20 M) for 40 minutes in a serum-free medium is shown in FIG. 7 for fluorescence change, and the relative ratio compared to the control group is shown in FIG. As a comparison group, the antioxidant N-acetyl-cysteine (NAC) was used.
도 7 및 8에서 확인할 수 있듯이, 미세먼지를 처리하면 망막색소상피세포 내에 활성산소종 생성이 증가하지만, 2-이소프로필말산이 처리되는 경우 활성산소종의 생성이 억제되는 것을 확인할 수 있었다.As can be seen in Figures 7 and 8, it was confirmed that the generation of reactive oxygen species in the retinal pigment epithelial cells increased when fine dust was treated, but the generation of reactive oxygen species was suppressed when 2-isopropylmalic acid was treated.
사이토카인 발현 평가Assessment of cytokine expression
실험예 2의 RPE/Smo-GFP에 미세먼지 (PM2.5)를 처리한 후, 2-이소프로필말산 100 μM을 24시간 처리하였다. 그 후, 세포 배양 상청액의 IL-6 및 TNF-α 수준을 ELISA kit(BD biosciences社)를 사용하여 측정하고, 그 결과를 도 9에 나타내었다. 비교군은 일차 섬모의 구조체를 형성하고 있는 주요 구성 단백질인 IFT88의 siRNA를 처리하였다.After fine dust (PM2.5) was treated with RPE/Smo-GFP of Experimental Example 2, 100 μM of 2-isopropylmalic acid was treated for 24 hours. Thereafter, the levels of IL-6 and TNF-α in the cell culture supernatant were measured using an ELISA kit (BD biosciences), and the results are shown in FIG. 9 . The control group was treated with siRNA of IFT88, a major constituent protein forming the structure of primary cilia.
도 9에서 확인할 수 있듯이, 미세먼지를 처리하면 염증 인자인 IL-6과 TNF-α이 증가하지만, 2-이소프로필말산이 처리되는 경우 IL-6과 TNF-α의 발현이 억제되는 것을 확인할 수 있었다.As can be seen in Figure 9, when fine dust is treated, the inflammatory factors IL-6 and TNF-α are increased, but when 2-isopropylmalic acid is treated, it can be seen that the expression of IL-6 and TNF-α is suppressed. there was.
[제형예 1] 액상 앰플제[Formulation Example 1] Liquid Ampoule
하기 표 1에 기재된 조성에 따라 통상적인 방법으로 액상 앰플제를 제조하였다.According to the composition shown in Table 1 below, liquid ampoules were prepared by a conventional method.
[제형예 2] 비누[Formulation Example 2] Soap
하기 표 2에 기재된 조성에 따라 통상적인 방법으로 비누를 제조하였다.Soap was prepared by a conventional method according to the composition shown in Table 2 below.
[제형예 3] 로션[Formulation Example 3] Lotion
하기 표 3에 기재된 조성에 따라 통상적인 방법으로 로션을 제조하였다.A lotion was prepared by a conventional method according to the composition shown in Table 3 below.
[제형예 4] 크림[Formulation Example 4] Cream
하기 표 4에 기재된 조성에 따라 통상적인 방법으로 크림을 제조하였다.Cream was prepared in a conventional manner according to the composition shown in Table 4 below.
[제형예 5] 팩[Formulation Example 5] Pack
하기 표 5에 기재된 조성에 따라 통상적인 방법으로 팩을 제조하였다.A pack was prepared in a conventional manner according to the composition shown in Table 5 below.
[제형예 6] 미용액형 제제[Formulation Example 6] Beauty liquid formulation
하기 표 6에 기재된 조성에 따라 통상적인 방법으로 미용액형 제제룰 제조하였다.According to the composition shown in Table 6 below, a cosmetic liquid formulation was prepared by a conventional method.
[제형예 7] 연질캅셀제[Formulation Example 7] Soft capsule preparation
2-이소프로필말산 100mg, L-카르니틴 160mg, 대두유 320mg, 팜유 2mg, 식물성 경화유 8mg, 황납 4mg 및 레시틴 6mg을 혼합하고, 통상의 방법에 따라 1캡슐에 충진하여 연질캅셀제를 제조하였다.100 mg of 2-isopropylmalic acid, 160 mg of L-carnitine, 320 mg of soybean oil, 2 mg of palm oil, 8 mg of hydrogenated vegetable oil, 4 mg of yellow wax, and 6 mg of lecithin were mixed and filled into 1 capsule according to a conventional method to prepare a soft capsule.
[제형예 8] 정제[Formulation Example 8] Tablets
2-이소프로필말산 100mg, 갈락토올리고당 500mg, 유당 80mg 및 맥아당 220mg을 혼합하고 유동층 건조기를 이용하여 과립한 후 당 에스테르(sugar ester)를 6mg을 첨가하여 타정기로 타정하여 정제를 제조하였다.100 mg of 2-isopropylmalic acid, 500 mg of galacto-oligosaccharide, 80 mg of lactose, and 220 mg of maltose were mixed and granulated using a fluidized bed dryer, and then 6 mg of sugar ester was added and tableted with a tableting machine to prepare tablets.
[제형예 9] 과립제[Formulation Example 9] Granules
2-이소프로필말산 100mg, 무수결정 포도당 250mg 및 전분 550mg을 혼합하고, 유동층 과립기를 사용하여 과립으로 성형한 후 포에 충진하여 과립제를 제조하였다.100 mg of 2-isopropylmalic acid, 250 mg of anhydrous crystalline glucose, and 550 mg of starch were mixed, molded into granules using a fluid bed granulator, and filled into bags to prepare granules.
[제형예 10] 드링크제[Formulation Example 10] Drinking agent
2-이소프로필말산 80mg, 포도당 10g, 구연산 0.6g, 및 액상 올리고당 25g을 혼합한 후 정제수 500ml를 가하여 각 병에 200ml씩 충진한다. 병에 충진한 후 130℃에서 4~5 초간 살균하여 드링크제 음료를 제조하였다.After mixing 80 mg of 2-isopropylmalic acid, 10 g of glucose, 0.6 g of citric acid, and 25 g of liquid oligosaccharide, 500 ml of purified water was added and each bottle was filled with 200 ml. After filling the bottle, it was sterilized at 130 ° C. for 4 to 5 seconds to prepare a drink beverage.
Claims (15)
상기 2-이소프로필말산(2-isopropylmalic acid), 이의 염, 수화물 또는 용매화물은 1.7 내지 90 mg/kg/일의 투여량으로 투여되는, 조성물.According to claim 1,
Wherein the 2-isopropylmalic acid (2-isopropylmalic acid), a salt, hydrate or solvate thereof is administered at a dosage of 1.7 to 90 mg/kg/day.
상기 눈 손상은 망막세포의 손상인 것인 조성물.According to claim 1,
Wherein the eye damage is damage to retinal cells.
상기 망막세포는 망막색소상피세포를 포함하는, 조성물.According to claim 3,
The retinal cells are composed of retinal pigment epithelial cells.
상기 눈 손상은 미세먼지에 의한 것인 조성물.According to claim 1,
The eye damage is a composition that is caused by fine dust.
상기 조성물은 식품 조성물인 조성물.According to any one of claims 1 to 5,
The composition is a food composition composition.
상기 조성물은 약학 조성물인 조성물.According to any one of claims 1 to 5,
Wherein the composition is a pharmaceutical composition.
상기 조성물은 화장료 조성물인 조성물.According to any one of claims 1 to 5,
The composition is a cosmetic composition composition.
상기 눈의 일차 섬모 활성화는 미세먼지에 의해 억제된 일차 섬모의 활성화인 조성물.According to claim 9,
The primary cilia activation of the eye is a composition in which the activation of primary cilia suppressed by fine dust.
상기 일차 섬모는 망막세포의 일차 섬모인 조성물.According to claim 9,
Wherein the primary cilia are primary cilia of retinal cells.
상기 2-이소프로필말산(2-isopropylmalic acid), 이의 염, 수화물 또는 용매화물은 1.7 내지 90 mg/kg/일의 투여량으로 투여되는 조성물.According to claim 9,
Wherein the 2-isopropylmalic acid (2-isopropylmalic acid), a salt, hydrate or solvate thereof is administered at a dosage of 1.7 to 90 mg/kg/day.
상기 조성물은 식품 조성물인 조성물.According to any one of claims 9 to 12,
The composition is a food composition composition.
상기 조성물은 약학 조성물인 조성물.According to any one of claims 9 to 12,
Wherein the composition is a pharmaceutical composition.
상기 조성물은 화장료 조성물인 조성물.According to any one of claims 9 to 12,
The composition is a cosmetic composition composition.
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