WO2018070707A1 - Composition for preventing or treating muscle disease comprising decanal or pharmaceutically acceptable salt thereof as active ingredient - Google Patents
Composition for preventing or treating muscle disease comprising decanal or pharmaceutically acceptable salt thereof as active ingredient Download PDFInfo
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- WO2018070707A1 WO2018070707A1 PCT/KR2017/010751 KR2017010751W WO2018070707A1 WO 2018070707 A1 WO2018070707 A1 WO 2018070707A1 KR 2017010751 W KR2017010751 W KR 2017010751W WO 2018070707 A1 WO2018070707 A1 WO 2018070707A1
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- Prior art keywords
- muscle
- decanal
- composition
- preventing
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Abstract
The present invention relates to a composition for preventing or treating a muscle disease or improving myofunction comprising decanal or a pharmaceutically acceptable salt thereof as an active ingredient and, more specifically, to a pharmaceutical composition for preventing or treating a muscle disease, a health functional food composition for preventing or improving a muscle disease, a pharmaceutical composition for promoting muscle differentiation or for regenerating or strengthening muscle, a health functional food composition for promoting muscle differentiation or for regenerating or strengthening muscle, a cosmetic composition for improving myofunction, and a livestock feed composition for preventing or treating a muscle disease, which comprise decanal or a pharmaceutically acceptable salt thereof as an active ingredient.
Description
본 출원은 2016년 10월 13일 출원된 대한민국 특허출원 제10-2016-0132845호를 우선권으로 주장하고, 상기 명세서 전체는 본 출원의 참고문헌이다.This application claims the priority of Korean Patent Application No. 10-2016-0132845, filed October 13, 2016, the entirety of which is a reference of the present application.
본 발명은 데칸알 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 질환 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing or treating muscle diseases comprising decanal or a pharmaceutically acceptable salt thereof as an active ingredient.
대한민국은 2000년 노인인구가 전체인구의 7.2%를 차지하여 고령화 사회에 진입하였으며, 2050년에는 초고령화사회(20% 이상)에 진입할 것으로 예측된다(2013년 고령자 통계, 통계청). 사람의 근육양은 나이가 들면서 감소하고(50~70세에 10~15% 정도, 70세~80세에서 30% 이상 감소), 이에 따라 근력과 근기능도 약화되는데, 이를 노인성 근감소증(sarcopenia)이라 한다. 노인성 근감소증은 활동장애와 보행장애를 유발하여 노인들의 독립적인 생활을 제한하는 주요 원인이 된다. 또한, 근감소증은 기초 대사율을 저하시켜 인슐린 저항성을 높이고 2형 당뇨병 발생을 촉진하며, 고혈압 및 심혈관계 질환 발생위험을 3-5배 증가시킨다. 현재 근감소증 치료용도로 승인된 의약품은 전무한 실정이며, myostatin 억제물질 또는 기존 FDA 승인을 받은 타질환 치료제를 근감소증에 적용하는 약물재배치(drug repositioning) 기술이 개발 중에 있다.In Korea, the elderly population accounted for 7.2% of the total population in 2000 and entered an aging society. In 2050, the aged population is expected to enter an aging society (more than 20%). Muscle mass in humans decreases with age (10-15% at 50-70 years, and more than 30% at 70-80 years), thereby weakening muscle strength and muscle function, which is called sarcopenia. do. Geriatric muscular dystrophy is a major cause of limiting the independent living of the elderly by inducing activity disorder and gait disorder. In addition, myopathy decreases basal metabolic rate, increases insulin resistance, promotes type 2 diabetes, and increases the risk of hypertension and cardiovascular disease by 3-5 times. Currently, no drug has been approved for the treatment of myopathy, and drug repositioning technology is being developed to apply myostatin inhibitor or other FDA-approved drugs to myopathy.
한편, 근육은 크게 골격근(skeletal muscle), 심장근(cardiac muscle), 평활근(visceral muscle)으로 구분되고, 이 중 골격근은 인체에서 가장 많은 양으로 존재하는 조직으로, 체중의 40-45%를 차지한다. 골격근은 건(tendon)을 통해 뼈(bone)에 붙어서 뼈의 움직임 또는 힘을 만들어 내는 역할을 한다. 하나의 근육은 수많은 근섬유로 구성되어 있으며, 다시 근섬유는 액틴과 미오신으로 구성된 수많은 근원섬유로 만들어진다. 액틴과 미오신이 서로 겹쳐서 움직이면 근육의 길이가 짧아지거나 길어지면서 전체적인 근육의 수축과 이완을 유발하게 된다. 근원섬유 크기의 증가는 근섬유 두께의 증가를 의미하고, 그 결과 근육의 증가가 일어나게 된다.Meanwhile, muscle is divided into skeletal muscle, cardiac muscle, and smooth muscle, and skeletal muscle is the most abundant tissue in the human body, and occupies 40-45% of body weight. . Skeletal muscles attach to bones through the tendons, creating bone movement or force. One muscle is made up of numerous myofibers, which in turn are made up of numerous myofibers composed of actin and myosin. When actin and myosin overlap each other, they shorten or lengthen the muscles, causing the entire muscle to contract and relax. An increase in myofibril size means an increase in myofiber thickness, resulting in an increase in muscle.
근육을 구성하는 근섬유의 유형은 ATP를 발생시키는 대사과정과 수축속도에 의해 주로 Type, Type ⅡA 그리고 Type B로 구분된다. '타입 근섬유'는 수축속도가 느리고 많은 수의 미오글로빈과 미토콘드리아를 함유하고 있어 지속적이면서 낮은 강도의 유산소활동을 하는데 적절하다. 타입 근섬유는 적색을 띄고 있어서 적색근이라고도 일컬어지며 대표적으로 가자미근(soleus)이 이에 속한다. 반면, '타입 B 근섬유'는 수축속도가 빨라 매우 짧지만 높은 강도의 무산소 운동을 하는데 쓰이며, 미오글로빈의 함량이 적어 백색을 띄고 있다. '타입 A 근섬유'는 앞서 언급한 두 가지 근섬유의 중간적인 특성을 띈다. 나이가 듦에 따라 근육의 부위별 타입, Ⅱ 근섬유의 조성이 달라질 뿐 아니라 모든 타입의 근섬유가 감소하게 된다.The types of muscle fibers that make up muscle are classified into Type, Type IIA and Type B mainly by the metabolic process and contraction rate that produce ATP. 'Type muscle fiber' has a slow contraction rate and contains a large number of myoglobin and mitochondria, which is suitable for continuous and low-intensity aerobic activity. Type muscle fibers have a red color and are also referred to as red muscles, and soleus is typical. On the other hand, 'Type B muscle fiber' is very short due to its fast shrinkage rate, but is used for high intensity anaerobic exercise, and has a low content of myoglobin, resulting in white color. Type A muscle fibers follow the intermediate characteristics of the two muscle fibers mentioned above. As you get older, the type of muscle and type II muscle fibers change, as well as all types of muscle fibers.
골격근은 환경에 따라 재생되어 유지되는 특징을 가지고 있으나, 이러한 특징은 나이가 듦에 따라 소실되고 결과적으로 노화가 진행되면서 근육양이 감소될 뿐 아니라 근력 역시 상실된다. 근육의 성장 및 재생에 관여하는 신호전달체계로는 insulin like growth factor 1(IGF-1)/AKT에 의해 매개되어 단백질 합성을 조절하는 신호전달이 있다. 근육세포막에 존재하는 IGF-1 receptor(IGF-1R)가 활성화되면 IRS1 및 PI3K 인산화를 통해 AKT 인산화가 증가되고 후자는 mTORC 인산화를 활성화시킨다. mTORC의 활성화는 ribosomal protein S6 kinase beta-1(P70S6K1)의 인산화를 증가시켜 mRNA 번역(translation)을 증가시키는 동시에 eukaryotic translation initiation factor 4 G(eIF4G)의 활성을 증가시키고, eukaryotic translation initiation factor 4E binding protein 1(4E-BP1) 단백질을 인산화시킨다. eIF4G와 4E-BP1은 eIF4F 복합체를 형성하는데 관여하는데 즉, eIF4G는 eIF4A 그리고 eIF4E와 결합하여 eIF4F 복합체를 형성하는 한편, 4E-BP1은 인산화되면 eIF4E와의 결합능이 저해되어 유리상태의 eIF4E를 증가시키게 된다. 후자는 다른 translation initiation factor들(eIF4G 및 eIF4A)와 결합하여 eIF4F 복합체를 형성하고, 이렇게 형성된 eIF4F 복합체는 리보솜 구조를 안정화시킴으로써 번역개시(translation initiation)를 촉진하여 궁극적으로 단백질 합성을 증가시키게 된다.Skeletal muscles have the characteristics of being regenerated and maintained according to the environment, but these characteristics are lost with age, and consequently, as aging progresses, muscle mass is reduced and muscle strength is also lost. Signaling systems involved in the growth and regeneration of muscle include signaling mediated by insulin like growth factor 1 (IGF-1) / AKT to regulate protein synthesis. The activation of IGF-1 receptor (IGF-1R) in the muscle cell membrane increases AKT phosphorylation through IRS1 and PI3K phosphorylation, and the latter activates mTORC phosphorylation. Activation of mTORC increases the phosphorylation of ribosomal protein S6 kinase beta-1 (P70S6K1), increases mRNA translation, increases eukaryotic translation initiation factor 4 G (eIF4G) activity, and eukaryotic translation initiation factor 4E binding protein Phosphorylate 1 (4E-BP1) protein. eIF4G and 4E-BP1 are involved in the formation of the eIF4F complex, that is, eIF4G binds to eIF4A and eIF4E to form an eIF4F complex, while phosphorylation of 4E-BP1 inhibits its binding to eIF4E, leading to an increase in free eIF4E. . The latter combines with other translation initiation factors (eIF4G and eIF4A) to form an eIF4F complex, which in turn promotes translation initiation by stabilizing ribosomal structures, ultimately increasing protein synthesis.
또한 AKT 인산화는 glycogen synthase kinase 3 (GSK3)를 통해 eIF2B발현을 증가시켜 근섬유 성장을 촉진시키는 한편 단백질 분해 관련 전사인자인 forkhead box O(FOXO)의 발현을 억제함으로써 근손실을 억제하기도 한다. 근손실은 myostatin, transforming growth factor beta(TGF-β), 그리고 activin을 포함하는 TGF-β family의 receptor에 의해 매개되는 신호전달에 의해 조절된다. TGF-β type II receptor에 리간드가 결합하면 type I receptor를 인산화시키고, 후자는 smad 2/3 complex를 인산화시켜 결국 FOXO를 활성화시킨다. 후자는 muscle-specific ubiquitin-ligase인 muscle RING-finger protein-1(MuRF1), Muscle Atrophy F-Box(MaFbx)/atrogin-1의 유전자 발현을 증가시키고, 이는 ubiquitin을 표적단백질의 lysine 부위에 부착시켜 단백질 분해를 촉진시키고, 결국 근육의 감소를 유도한다. In addition, AKT phosphorylation stimulates muscle fiber growth by increasing eIF2B expression through glycogen synthase kinase 3 (GSK3) and also inhibits muscle loss by inhibiting the expression of forkhead box O (FOXO), a protein-related transcription factor. Muscle loss is regulated by signaling mediated by receptors of the TGF-β family, including myostatin, transforming growth factor beta (TGF-β), and activin. Binding of the ligand to the TGF-β type II receptor phosphorylates the type I receptor, the latter phosphorylates the smad 2/3 complex and eventually activates FOXO. The latter increases the gene expression of muscle-specific ubiquitin-ligase, muscle RING-finger protein-1 (MuRF1) and Muscle Atrophy F-Box (MaFbx) / atrogin-1, which attach ubiquitin to the lysine site of the target protein. Promote proteolysis, eventually leading to muscle loss.
따라서 본 발명자들은 부작용이 적은 천연물에서 근육 단백질의 분해작용을 억제하고 합성을 촉진시킴으로써 근육의 증강 및 근손실 개선에 효과가 있는 식품 소재를 개발하고자 하였다.Therefore, the present inventors have attempted to develop a food material that is effective in improving muscles and improving muscle loss by inhibiting the degradation of muscle proteins and promoting synthesis in natural products with few side effects.
이에 본 발명자들은 부작용 없이 근육 질환을 예방 또는 치료할 수 있는 천연 유래 화합물을 밝혀내고자 노력하였다. 그 결과, 데칸알의 근육 증강 및 근 손실 작용 기작을 규명하였다.The present inventors have tried to find a naturally derived compound that can prevent or treat muscle diseases without side effects. As a result, the mechanism of muscle enhancement and muscle loss action of decanal was identified.
따라서, 본 발명의 목적은 상기와 같은 문제점을 해결하기 위해 안출된 것으로, 하기 화학식 1로 표시되는 데칸알(Decanal) 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 질환 예방 또는 치료용 약학적 조성물을 제공하는 것이다.Accordingly, an object of the present invention is to solve the above problems, prevent or treat muscle diseases comprising a decanal compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient It is to provide a pharmaceutical composition.
[화학식 1][Formula 1]
본 발명의 또 다른 목적은 데칸알(Decanal) 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 질환 예방 또는 개선용 건강기능성 식품 조성물을 제공하는 것이다.Still another object of the present invention is to provide a health functional food composition for preventing or improving muscle diseases including a decanal compound or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명의 또 다른 목적은 데칸알(Decanal) 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 분화 촉진, 근육 재생 또는 근육 강화용 약학적 조성물을 제공하는 것이다.Still another object of the present invention is to provide a pharmaceutical composition for promoting muscle differentiation, muscle regeneration, or muscle strengthening, including a decanal compound or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명의 또 다른 목적은 데칸알(Decanal) 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 분화 촉진, 근육 재생 또는 근육 강화용 건강기능성 식품 조성물을 제공하는 것이다. Still another object of the present invention is to provide a health functional food composition for promoting muscle differentiation, muscle regeneration or muscle enhancement, including a decanal compound or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명의 또 다른 목적은 데칸알(Decanal) 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근기능 개선용 화장료 조성물을 제공하는 것이다.Still another object of the present invention is to provide a decanal compound or a pharmaceutical composition for improving muscle function, including a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명의 또 다른 목적은 데칸알(Decanal) 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 질환 예방 또는 치료용 가축사료용 조성물을 제공하는 것이다. Still another object of the present invention is to provide a composition for animal feed for preventing or treating muscle diseases, including a decanal compound or a pharmaceutically acceptable salt thereof as an active ingredient.
또한, 본 발명은 데칸알 또는 이의 약제학적으로 허용 가능한 염을 유효성분으로 포함하는 조성물을 투여하는 것을 포함한 근육 질환 예방 또는 치료 위한 방법을 제공하고자 한다.In addition, the present invention is to provide a method for preventing or treating muscle diseases, including administering a composition comprising decanal or a pharmaceutically acceptable salt thereof as an active ingredient.
더 나아가, 본 발명은 근육 질환 예방 또는 치료제의 제조를 위한 데칸알 또는 이의 약제학적으로 허용 가능한 염을 유효성분으로 포함하는 조성물의 용도를 제공하고자 한다. Furthermore, the present invention is to provide a use of a composition comprising decanal or a pharmaceutically acceptable salt thereof as an active ingredient for the preparation of a preventive or therapeutic agent for muscle diseases.
그러나, 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당업자에게 명확하게 이해될 수 있을 것이다.However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problem, another task that is not mentioned will be clearly understood by those skilled in the art from the following description.
따라서, 본 발명은 하기 화학식 1로 표시되는 데칸알(Decanal) 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 질환 예방 또는 치료용 약학적 조성물을 제공한다.Accordingly, the present invention provides a pharmaceutical composition for preventing or treating muscle diseases comprising a decanal compound represented by the following Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
[화학식 1][Formula 1]
본 발명의 바람직한 일실시예에 따르면, 상기 조성물은 p-4E-BP1 또는 p-p70S6K1 단백질의 발현을 증가시키는 것일 수 있다.According to a preferred embodiment of the present invention, the composition may be to increase the expression of p-4E-BP1 or p-p70S6K1 protein.
본 발명의 바람직한 다른 일실시예에 따르면, 상기 조성물은 MuRF1(Muscle Ring-Finger Protein) 또는 MaFbx(Muscle atrophy F-box)의 발현을 감소시키는 것일 수 있다. According to another preferred embodiment of the present invention, the composition may be to reduce the expression of MuRF1 (Muscle Ring-Finger Protein) or MaFbx (Muscle atrophy F-box).
본 발명의 바람직한 또 다른 일실시예에 따르면, 상기 화합물은 0.1 내지 1000μM의 농도로 조성물에 포함되는 것일 수 있다. According to another preferred embodiment of the present invention, the compound may be included in the composition at a concentration of 0.1 to 1000μM.
본 발명의 바람직한 또 다른 일실시예에 따르면, 상기 근육 질환은 근 기능 저하, 근육 감소, 근육 소모 또는 근육 퇴화로 인한 근육 질환인 것일 수 있다.According to another preferred embodiment of the present invention, the muscle disease may be a muscle disease due to muscle function degradation, muscle reduction, muscle wasting or muscle degeneration.
본 발명의 바람직한 또 다른 일실시예에 따르면, 상기 근육 질환은 긴장감퇴증(atony), 근위축증(muscular atrophy), 근이영양증(muscular dystrophy), 근무력증, 악액질(cachexia), 경직성 척추 증후군(rigid spinesyndrome), 근위축성 측삭경화증(루게릭병, amyotrophic lateral sclerosis), 경직성 척추 증후군(rigid spinsesyndrome), 샤르코-마리-투스병(Charcot-Marie-Tooth disease) 및 근육 감소증(sarcopenia)으로 이루어진 군으로부터 선택되는 어느 하나 이상인 것일 수 있다. According to another preferred embodiment of the present invention, the muscle disease is atony, muscular atrophy, muscular dystrophy, ataxia, cachexia, rigid spinesyndrome, At least one selected from the group consisting of amyotrophic lateral sclerosis, rigid spinse syndrome, Charcot-Marie-Tooth disease and sarcopenia It may be.
또한, 본 발명은 데칸알(Decanal) 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 질환 예방 또는 개선용 건강기능성 식품 조성물을 제공한다.In addition, the present invention provides a decanal compound or a health functional food composition for preventing or improving muscle diseases, including a pharmaceutically acceptable salt thereof as an active ingredient.
또한, 본 발명은 데칸알(Decanal) 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 분화 촉진, 근육 재생 또는 근육 강화용 약학적 조성물을 제공한다. In addition, the present invention provides a pharmaceutical composition for promoting muscle differentiation, muscle regeneration or muscle enhancement, including a decanal compound or a pharmaceutically acceptable salt thereof as an active ingredient.
또한, 본 발명은 데칸알(Decanal) 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 분화 촉진, 근육 재생 또는 근육 강화용 건강기능성 식품 조성물을 제공한다. The present invention also provides a health functional food composition for promoting muscle differentiation, muscle regeneration, or muscle strengthening, including a decanal compound or a pharmaceutically acceptable salt thereof as an active ingredient.
또한, 본 발명은 데칸알(Decanal) 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근기능 개선용 화장료 조성물을 제공한다.The present invention also provides a decanal compound (Decanal) or a pharmaceutically acceptable salt thereof as an active ingredient provides a cosmetic composition for improving muscle function.
또한, 본 발명은 데칸알(Decanal) 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 질환 예방 또는 치료용 가축사료용 조성물을 제공한다.In addition, the present invention provides a composition for animal feed for the prevention or treatment of muscle diseases comprising a decanal compound (Decanal) or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명의 바람직한 일실시예에 따르면, 상기 가축은 소, 돼지, 닭, 오리, 염소, 양 및 말로 이루어진 군 중에서 선택된 1종의 가축인 것일 수 있다. According to a preferred embodiment of the present invention, the livestock may be one livestock selected from the group consisting of cattle, pigs, chickens, ducks, goats, sheep and horses.
본 발명은 데칸알(Decanal) 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 질환 예방 또는 치료용, 또는 근 기능 개선용 조성물에 관한 것으로, 상기 데칸알은 근육 세포에서 근단백질 합성 및 근육량 증가와 관련된 단백질의 발현을 증가시킬 수 있으며, 근 단백질 분해에 관여하는 효소의 발현은 mRNA 수준에서부터 억제할 수 있으므로 근기능 저하, 근육 소모 또는 근육 퇴화로 인한 근육 질환에 있어서 근육 분화, 근육 재생, 근육량 증가를 통해 근력 강화 효과를 나타낼 수 있으며, 근육 감소를 억제할 수 있다. 또한, 고지방식이 섭취에 따른 근 손실 및 근력 약화를 개선시킬 수 있다. The present invention relates to a composition for preventing or treating muscle diseases, or improving muscle function, comprising decanal or a pharmaceutically acceptable salt thereof as an active ingredient, wherein the decanal is used to synthesize muscle protein in muscle cells and It is possible to increase the expression of proteins associated with increased muscle mass, and the expression of enzymes involved in muscle protein degradation can be suppressed from the mRNA level, so muscle differentiation, muscle regeneration, Increasing muscle mass can increase muscle strength and inhibit muscle loss. In addition, high fat diets may improve muscle loss and muscle weakness associated with ingestion.
따라서, 본 발명의 조성물은 근육 질환 예방 또는 치료용, 근육 분화, 근육 재생 및 근육량 증가용 또는 근 기능 개선에 이용될 수 있다.Therefore, the composition of the present invention can be used for preventing or treating muscle diseases, muscle differentiation, muscle regeneration and muscle mass increase or muscle function improvement.
도 1은 마우스근아세포에서 근관세포의 두께 변화를 나타낸 것이다. 도 1a는 giemsa-wright 염색한 근관세포를 현미경으로 촬영하여 시각화한 것이고, 도 1b는 근관세포의 직경을 측정한 결과이며 각 값들은 세 개의 독립된 well에서 세 번의 결정 값의 평균±표준오차이다. P <0.05는 통계적 유의성을 나타낸다Figure 1 shows the change in the thickness of myotubes in mouse myoblasts. FIG. 1A is a microscopic image of giemsa-wright stained root canal cells, and FIG. 1B is a result of measuring the diameter of the root canal cells, and each value is the mean ± standard error of three crystals in three independent wells. P <0.05 indicates statistical significance
도 2는 데칸알을 처리한 마우스근아세포에서 단백질 분해 및 합성 관련 분자들의 발현 변화를 나타낸 것이다. 도 2a는 p-4E-BP1, Total 4E-BP1, p-p70S6K1, 및 Total p70S6K1의 단백질 수준을 나타낸 것이고, 도 2b는 MaFbx 및 MuRF1의 유전자 발현 수준을 나타낸 것이다. 각 값들은 세 개의 독립된 well에서 세 번의 결정 값의 평균±표준오차이다. P <0.05는 통계적 유의성을 나타낸다.Figure 2 shows the expression changes of molecules related to protein degradation and synthesis in mouse myoblasts treated with decanal. 2A shows the protein levels of p-4E-BP1, Total 4E-BP1, p-p70S6K1, and Total p70S6K1, and FIG. 2B shows the gene expression levels of MaFbx and MuRF1. Each value is the mean ± standard error of three determinations in three independent wells. P <0.05 indicates statistical significance.
도 3은 데칸알 섭취에 의한 마우스 사지근력 증가 결과를 나타낸 그래프이다.Figure 3 is a graph showing the results of the increase in the muscle extremities muscle intake by decanal.
도 4는 데칸알 섭취에 의한 마우스 근육조직의 근섬유 직경 변화를 나타낸 그래프이다. 도 4a는 rectus femoris, 4b는 soleus, 4c는 gastrocnemius muscle tissues를 나타낸다. Figure 4 is a graph showing the change in muscle fiber diameter of mouse muscle tissue by decanal intake. 4a shows rectus femoris, 4b soleus, and 4c gastrocnemius muscle tissues.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
상술한 바와 같이, 우수한 근 기능 조절 활성을 가지며 안전하게 적용될 수 있는 물질의 탐색이 계속 요구되고 있으나, 데칸알이 근육 질환 및 근 기능 개선에 대하여 나타내는 효과에 관한 연구는 아직까지 보고된 바 없다. As described above, the search for a substance that has excellent muscle function regulating activity and can be applied safely is still required, but studies on the effects of decanal on muscle disease and muscle function improvement have not been reported until now.
본 발명에 따른 데칸알은 근육 세포에서 근 단백질 합성 및 근육량 증가와 관련된 단백질의 발현을 증가시킬 수 있으므로, 근 기능 저하, 근육 소모 또는 근육 퇴화로 인한 근육 질환에 있어서 근육량 증가 효과를 나타낼 수 있어 근육 질환 예방 또는 치료용 조성물의 유효성분으로 효과적이다.Deccanal according to the present invention can increase the expression of proteins related to muscle protein synthesis and muscle mass increase in muscle cells, can exhibit an effect of increasing muscle mass in muscle diseases caused by muscle function degradation, muscle wasting or muscle degeneration It is effective as an active ingredient of a composition for preventing or treating diseases.
따라서, 본 발명은 하기 화학식 1로 표시되는 데칸알(Decanal)화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 질환 예방 또는 치료용 약학적 조성물을 제공한다.Accordingly, the present invention provides a pharmaceutical composition for preventing or treating muscle diseases comprising a decanal compound represented by Formula 1 below or a pharmaceutically acceptable salt thereof as an active ingredient.
[화학식 1][Formula 1]
본 발명의 용어 "데칸알(Decanal)"은 알데히드(aldehyde)계 화합물로서, 화학물질고유번호(CAS No.) 112-31-2로서 표시될 수 있으며, aldehyde C-10, caprinaldehyde, decyl aldehyde, decanaldehyde 등의 이명으로도 명명된다.The term "decanal" of the present invention is an aldehyde-based compound, which may be represented as chemical identification number (CAS No.) 112-31-2, aldehyde C-10, caprinaldehyde, decyl aldehyde, Also known as tinnitus such as decanaldehyde.
데칸알은 착항제와 항료로 많이 사용되고 있으며, 그동안 보고된 데칸알의 생리활성으로는 데칸알을 성게와 요각류(검물벼룩 등의 수생(水生) 동물)의 embryos cell에 처리한 결과, apoptosis를 유발함으로써 reproductive failure를 유도한다고 보고되고(Romano et al. A marine diatom-derived aldehyde induces apoptosis in copepod and sea urchin embryos. Journal of Experimental Biology 206: 3487-3494, 2003), 데칸알과 N-amino-N’-1-octylguanidine (AOG)을 혼합시켜서 종양세포인 HeLa cell과 bacteria에 처리한 결과, synergistic activity 효과를 내며 성장을 저해시킨다는 것이 보고되었으며(Rideout et al. Self-assembling cytotoxins. Science 233: 561-563, 1986), 데칸알의 강력한 살선충 활성(nematicidal activity)으로 인해 식물의 뿌리에 기생하는 선충을 번식을 차단하고 억제하는 효과가 있음이 보고되었다(Kim et al. Nematicidal activity of plant essential oils and components from coriander (Coriandrum sativum), oriental sweetgum (Liquidambar orientalis), and valerian (Valeriana wallichii) essential oils against pine wood nematode (Bursaphelenchus xylophilus). Journal of Agricultural and Food Chemistry 56: 7316-7320, 2008). Deccanal is widely used as an anti-drug agent and as a medicine. The biological activity of decanal reported so far is that decanal is treated in embryos cells of sea urchins and copepods (aquatic animals such as black fleas), causing apoptosis. By inducing reproductive failure (Romano et al. A marine diatom-derived aldehyde induces apoptosis in copepod and sea urchin embryos.Journal of Experimental Biology 206: 3487-3494, 2003), decanal and N-amino-N ' The treatment of -1-octylguanidine (AOG) with tumor cells, HeLa cells and bacteria, has been reported to produce synergistic activity and inhibit growth (Rideout et al. Self-assembling cytotoxins.Science 233: 561-563 , 1986) It has been reported that decanal's potent nematicidal activity blocks and inhibits the reproduction of parasitic nematodes in the roots of plants (Kim et al. Nematicidal activity of plant es). sential oils and components from coriander (Coriandrum sativum), oriental sweetgum (Liquidambar orientalis), and valerian (Valeriana wallichii) essential oils against pine wood nematode (Bursaphelenchus xylophilus) .Journal of Agricultural and Food Chemistry 56: 7316-7320, 2008.
그러나, 본 발명에서는 데칸알이 근관세포(myotube)의 두께를 증가시키고, 근 단백질 합성 및 근육량 증가와 관련된 단백질의 발현을 증가시키며 근 단백질의 분해를 촉진시키는 유전자의 발현을 감소시킴으로써 근육 관련 질환의 예방 또는 치료 효과가 있음을 확인할 수 있었다. However, in the present invention, decanal increases the thickness of myotubes, increases the expression of proteins associated with muscle protein synthesis and muscle mass, and reduces the expression of genes that promote the degradation of muscle proteins. It was confirmed that there is a prophylactic or therapeutic effect.
본 발명의 조성물은 p-4E-BP1 또는 p-p70S6K1 단백질의 발현을 증가시키는 것을 특징으로 할 수 있다.The composition of the present invention may be characterized by increasing the expression of p-4E-BP1 or p-p70S6K1 protein.
또한, 본 발명의 조성물은 MuRF1(Muscle Ring-Finger Protein) 또는 MaFbx(Muscle atrophy F-box)의 발현을 감소시키는 것을 특징으로 할 수 있다.In addition, the composition of the present invention may be characterized by reducing the expression of the MuRF1 (Muscle Ring-Finger Protein) or MaFbx (Muscle atrophy F-box).
구체적으로, 단백질 합성과 관련이 있는 대표적인 분자로는 p70S6K1, 4E-BP1 및 eIF members가 있고, 이 세 가지 분자들은 상위의 mTORC에 의해 활성이 조절된다. mTORc의 활성화는 p70S6K1를 인산화시키고, 활성화된 p70S6K1은 40S 리보솜단백질(ribosomal protein) S6를 인산화시켜서 mRNA 번역(translation)을 증가시키게 된다. 또한 mTORC의 활성화는 eIF4G의 활성을 증가시키는 동시에 4E-BP1을 인산화시키는데, 이 두 분자는 eIF4F 복합체를 형성하는데 관여한다. 즉, eIF4G는 eIF4A 그리고 eIF4E와 결합하여 eIF4F 복합체를 형성하는 한편, 4E-BP1은 인산화되면 eIF4E와의 결합능이 저해되어 유리상태의 eIF4E를 증가시키게 된다. 후자는 다른 translation initiation factor들(eIF4G 및 eIF4A)와 결합하여 eIF4F 복합체를 형성하고, 이렇게 형성된 eIF4F 복합체는 리보솜 구조를 안정화시킴으로써 번역개시(translation initiation)를 촉진하여 궁극적으로 단백질 합성을 증가시키게 된다. MAFbx/Atrogin-1과 MuRF1은 muscle-specific ubiquitin-ligase로, ubiquitin을 표적단백질의 lysine 부위에 부착시켜 단백질 분해를 촉진시키고, 결국 근육의 감소를 유도하는 대표적인 단백질이다. Specifically, representative molecules related to protein synthesis include p70S6K1, 4E-BP1, and eIF members, and these three molecules are regulated by higher mTORCs. Activation of mTORc phosphorylates p70S6K1 and activated p70S6K1 phosphorylates 40S ribosomal protein S6 to increase mRNA translation. Activation of mTORC also increases the activity of eIF4G and simultaneously phosphorylates 4E-BP1, both molecules involved in forming the eIF4F complex. That is, eIF4G binds to eIF4A and eIF4E to form an eIF4F complex, while when 4E-BP1 is phosphorylated, its binding ability with eIF4E is inhibited to increase the free eIF4E. The latter combines with other translation initiation factors (eIF4G and eIF4A) to form an eIF4F complex, which in turn promotes translation initiation by stabilizing ribosomal structures, ultimately increasing protein synthesis. MAFbx / Atrogin-1 and MuRF1 are muscle-specific ubiquitin-ligases, which are representative proteins that attach ubiquitin to the lysine site of the target protein to promote protein degradation and ultimately muscle loss.
본 발명의 실시예 2에서 나타난 바와 같이, 본 발명의 조성물은 단백질 합성 및 분해 관련 분자들의 발현을 변화시킴을 확인할 수 있었다. 구체적으로, 데칸알을 처리한 마우스근아세포에서 dexamethasone처리에 의해 감소된 단백질 합성에 관여하는 p-4E-BP1 및 p-p70S6K1 단백질의 발현이 유의적으로 증가하는 것을 확인할 수 있었다. 반면, 근 단백질의 분해를 촉진시킴으로써 근육의 감소를 유도하는 MaFbx 및 MuRF1의 mRTA 발현량은 유의적으로 감소하는 것을 확인할 수 있었다. 이를 통해, 본 발명의 조성물은 p-4E-BP1 및 p-p70S6K1 단백질 인산화를 증가시키고, MuRF1 및 MaFbx 유전자 발현을 억제함으로써 근 손실을 감소하고 근육의 양을 증가시킬 수 있음을 확인할 수 있었다. As shown in Example 2 of the present invention, the composition of the present invention was confirmed to change the expression of molecules related to protein synthesis and degradation. Specifically, it was confirmed that the expression of p-4E-BP1 and p-p70S6K1 proteins involved in protein synthesis decreased by dexamethasone treatment in mouse myoblasts treated with decanal was significantly increased. On the other hand, it was confirmed that the expression of mRTA of MaFbx and MuRF1 significantly reduced muscle induction by promoting muscle protein degradation. Through this, the composition of the present invention was confirmed that by increasing the p-4E-BP1 and p-p70S6K1 protein phosphorylation, by inhibiting MuRF1 and MaFbx gene expression can reduce muscle loss and increase the amount of muscle.
더불어, 상기 근육 질환 예방 또는 치료용 약학적 조성물은 데칸알 또는 이의 약학적으로 허용 가능한 염을 포함하는 것이라면 그 함량을 특별히 제한하지는 않으나, 바람직하게는 0.1 내지 1000μM의 농도로 포함할 수 있고, 보다 바람직하게는 0.1 내지 500μM의 농도를 포함할 수 있으며, 더욱 바람직하게는 1 내지 100μM의 농도를 포함할 수 있다. 구체적으로, 본 발명의 실시예 1에서 나타난 바와 같이, 데칸알 100μM을 처리한 마우스근아세포에서 dexamethoasone 처리에 의해 감소한 근관세포의 두께가 74% 증가하는 것을 확인할 수 있었다. In addition, the pharmaceutical composition for preventing or treating muscle diseases does not specifically limit the content as long as it contains decanal or a pharmaceutically acceptable salt thereof, and preferably may be included in a concentration of 0.1 to 1000 μM, more Preferably it may comprise a concentration of 0.1 to 500μM, more preferably may comprise a concentration of 1 to 100μM. Specifically, as shown in Example 1 of the present invention, it was confirmed that the myofiocytes treated with decanal 100μM increased 74% in thickness of myotubes reduced by dexamethoasone treatment.
또한, 본 발명의 근육질환은 근 기능 저하, 근육 감소, 근육 소모 또는 근육 퇴화로 인한 근육 질환으로 당업계에 보고된 질병인 것이 바람직하며, 구체적으로 긴장감퇴증(atony), 근위축증(muscular atrophy), 근이영양증(muscular dystrophy), 근무력증, 악액질(cachexia), 경직성 척추 증후군(rigid spinesyndrome), 근위축성 측삭경화증(루게릭병, amyotrophic lateral sclerosis), 경직성 척추 증후군(rigid spinsesyndrome), 샤르코-마리-투스병(Charcot-Marie-Tooth disease) 및 근육 감소증(sarcopenia)으로 이루어진 군으로부터 선택되는 어느 하나 이상인 것이 더욱 바람직하나, 이에 제한되는 것은 아니다. In addition, the muscle disease of the present invention is preferably a disease reported in the art as a muscle disease caused by muscle function decline, muscle loss, muscle wasting or muscle degeneration, and specifically, atony, muscular atrophy , Muscular dystrophy, muscular dystrophy, cachexia, rigid spinesyndrome, amyotrophic lateral sclerosis, rigid spinse syndrome, Sharco-Marie-Tus disease ( Charcot-Marie-Tooth disease) and sarcopenia is more preferably any one or more selected from the group consisting of, but is not limited thereto.
또한, 본 발명은 하기 화학식 1로 표시되는 데칸알(Decanal) 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 분화 촉진, 근육 재생 또는 근육 강화용 약학적 조성물을 제공한다. 상기 데칸알의 구체적인 내용은 전술한 바와 같다. In addition, the present invention provides a pharmaceutical composition for promoting muscle differentiation, muscle regeneration or muscle strengthening comprising a decanal compound represented by the following Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. Details of the decanal are as described above.
[화학식 1][Formula 1]
상기 근육 소모 또는 퇴화는 전적 요인, 후천적 요인, 노화 등을 원인으로 발생하며, 근육 소모는 근육량의 점진적 손실, 근육, 특히 골격근 또는 수의근 및 심장근육의 약화 및 퇴행을 특징으로 한다.The muscle wasting or degeneration is caused by a total factor, acquired factors, aging, etc., muscle wasting is characterized by a gradual loss of muscle mass, muscle weakness, especially skeletal muscle or veterinary muscle and heart muscle.
보다 구체적으로, 상기 근육은 심줄, 근육, 건을 포괄적으로 지칭하고, 근 기능 또는 근육 기능은 근육의 수축에 의해 힘을 발휘할 수 있는 능력을 의미하며, 근육이 저항을 이겨내기 위하여 최대한의 수축력을 발휘할 수 있는 근력; 근육이 주어진 중량에 얼마나 오랫동안 또는 얼마나 여러 번 수축과 이완을 반복할 수 있는지 나타내는 능력인 근 지구력; 및 단시간 내에 강한 힘을 발휘하는 능력인 순발력을 포함한다. 상기 근 기능은 간이 주관하며, 근육량에 비례한다. 본 발명의 용어 "근기능 개선"은 근 기능을 보다 긍정적인 방향으로 향상시키는 것을 의미한다.More specifically, the muscle refers to tendons, muscles, and tendons collectively, muscle function or muscle function refers to the ability to exert a force by the contraction of the muscle, the muscle to the maximum contraction force to overcome the resistance Muscle strength that can be exerted; Muscle endurance, the ability to indicate how long or how many times a muscle can repeat contraction and relaxation at a given weight; And quickness, which is the ability to exert a strong force in a short time. The muscle function is dominated by the liver and is proportional to muscle mass. The term "improving muscle function" of the present invention means improving muscle function in a more positive direction.
본 발명의 근육 질환 예방 및 치료용 또는 근 기능 개선용 조성물은 데칸알을 단독으로 함유하거나 또는 데칸알과 그의 유사한 기능을 나타내는 유효성분을 1종 이상 함유할 수 있다. 추가적인 성분을 포함하게 되면 본 발명의 조성물의 근 기능 개선 효과가 더욱 증진될 수 있을 것이다. 상기 성분 추가 시에는 복합 사용에 따른 피부 안전성, 제형화의 용이성, 유효성분들의 안정성을 고려할 수 있다.The composition for preventing and treating muscle diseases or improving muscle function of the present invention may contain decanal alone or one or more active ingredients exhibiting similar functions with decanal. Inclusion of additional components may further enhance the muscle function improving effect of the composition of the present invention. When the ingredient is added, skin safety, ease of formulation, and stability of the active ingredients may be considered.
본 발명의 약학 조성물은 데칸알을 약제학적으로 허용 가능한 염을 포함할 수 있다. 본 발명의 용어“약학적으로 허용 가능한”이란 생리학적으로 허용되고 인간에게 투여될 때, 통상적으로 알레르기 반응 또는 이와 유사한 반응을 일으키지 않는 것을 말하며, 상기 염으로는 약제학적으로 허용 가능한 유리산(free acid)에 의하여 형성된 산 부가염이 바람직하다.The pharmaceutical composition of the present invention may comprise a pharmaceutically acceptable salt of decanal. As used herein, the term “pharmaceutically acceptable” refers to a physiologically acceptable and normally does not cause an allergic or similar reaction when administered to a human, wherein the salt is a pharmaceutically acceptable free acid. Acid addition salts formed by acid) are preferred.
상기 데칸알의 약학적으로 허용 가능한 염은 유기산 또는 무기산을 이용하여 형성된 산 부가염일 수 있으며, 상기 유기산은 예를 들면 포름산, 아세트산, 프로피온산, 락트산, 부티르산, 이소부티르산, 트리플루오로아세트산, 말산, 말레산, 말론산, 푸마르산, 숙신산, 숙신산 모노아미드, 글루탐산, 타르타르산, 옥살산, 시트르산, 글리콜산, 글루쿠론산, 아스코르브산, 벤조산, 프탈산, 살리실산, 안트라닐산, 디클로로아세트산, 아미노옥시 아세트산, 벤젠술폰산, p-톨루엔술폰산 또는 메탄술폰산을 포함한다. 무기산은 예를 들면 염산, 브롬산, 황산, 인산, 질산, 탄산 또는 붕산을 포함한다. 산 부가염은 바람직하게는 염산염 또는 아세트산염 형태일 수 있으며, 보다 바람직하게는 염산염 형태일 수 있다.The pharmaceutically acceptable salt of the decanal may be an acid addition salt formed using an organic acid or an inorganic acid, and the organic acid may be, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid, malic acid, Maleic acid, malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid, glycolic acid, glucuronic acid, ascorbic acid, benzoic acid, phthalic acid, salicylic acid, anthranilic acid, dichloroacetic acid, aminooxyacetic acid, benzenesulfonic acid , p-toluenesulfonic acid or methanesulfonic acid. Inorganic acids include, for example, hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid or boric acid. The acid addition salt may preferably be in the form of hydrochloride or acetate, more preferably in the form of hydrochloride.
상기 언급된 산 부가염은 a) 데칸알 및 산을 직접 혼합하거나, b) 이를 용매 또는 함수 용매 중에 용해시키고 혼합시키거나, 또는 c) 데칸알을 용매 또는 수하 용매 중의 산에 위치시키고 이들을 혼합하는 일반적인 염 제조방법으로 제조된다.The above-mentioned acid addition salts may be prepared by either a) mixing the decanal and acid directly, b) dissolving and mixing it in a solvent or hydrous solvent, or c) placing the decanal in an acid in a solvent or submerged solvent and mixing them. It is prepared by a general salt preparation method.
위와는 별도로 추가적으로 염이 가능한 형태는 가바염, 가바펜틴염, 프레가발린염, 니코틴산염, 아디페이트염, 헤미말론산염, 시스테인염, 아세틸시스테인염, 메티오닌염, 아르기닌염, 라이신염, 오르니틴염 또는 아스파르트산염 등이 있다.In addition to the above, salts that can be additionally salted are gabar salt, gabapentin salt, pregabalin salt, nicotinate, adipate salt, hemimalonate, cysteine salt, acetylcysteine salt, methionine salt, arginine salt, lysine salt, ornithine salt Aspartate.
또한, 본 발명의 근육 질환 예방 및 치료용 약학 조성물은 약학적으로 허용 가능한 담체를 더 포함할 수 있다.In addition, the pharmaceutical composition for preventing and treating muscle diseases of the present invention may further include a pharmaceutically acceptable carrier.
약학적으로 허용되는 담체로는 예컨대, 경구 투여용 담체 또는 비경구 투여용 담체를 추가로 포함할 수 있다. 경구 투여용 담체는 락토스, 전분, 셀룰로스 유도체, 마그네슘 스테아레이트, 스테아르산 등을 포함할 수 있다. 또한 비경구 투여용 담체는 물, 적합한 오일, 식염수, 수성 글루코스 및 글리콜 등을 포함할 수 있다. 또한, 안정화제 및 보존제를 추가로 포함할 수 있다. 적합한 안정화제로는 아황산수소나트륨, 아황산나트륨 또는 아스코르브산과 같은 항산화제가 있다. 적합한 보존제로는 벤즈알코늄 클로라이드, 메틸- 또는 프로필-파라벤 및 클로로부탄올이 있다. 그 밖의 약학적으로 허용되는 담체로는 다음의 문헌에 기재되어 있는 것을 참고로 할 수 있다(Remington's Pharmaceutical Sciences, 19th ed., Mack Publishing Company, Easton, PA, 1995).Pharmaceutically acceptable carriers may further include, for example, carriers for oral administration or carriers for parenteral administration. Carriers for oral administration may include lactose, starch, cellulose derivatives, magnesium stearate, stearic acid and the like. Carriers for parenteral administration may also include water, suitable oils, saline, aqueous glucose, glycols, and the like. In addition, stabilizers and preservatives may be further included. Suitable stabilizers include antioxidants such as sodium hydrogen sulfite, sodium sulfite or ascorbic acid. Suitable preservatives include benzalkonium chloride, methyl- or propyl-paraben and chlorobutanol. Other pharmaceutically acceptable carriers may be referred to those described in the following documents (Remington's Pharmaceutical Sciences, 19th ed., Mack Publishing Company, Easton, PA, 1995).
본 발명의 약학 조성물은 인간을 비롯한 포유동물에 어떠한 방법으로도 투여할 수 있다. 예를 들어, 경구 또는 비경구로 투여할 수 있으며, 비경구적인 투여방법으로는 이에 제한되는 것은 아니나, 정맥내, 근육내, 동맥내, 골수내, 경막내, 심장내, 경피, 피하, 복강내, 비강내, 장관, 국소, 설하 또는 직장내 투여일 수 있다.The pharmaceutical composition of the present invention can be administered to any mammal, including humans. For example, it can be administered orally or parenterally, parenteral administration methods include, but are not limited to, intravenous, intramuscular, intraarterial, intramedullary, intradural, intracardiac, transdermal, subcutaneous, intraperitoneal , Intranasal, intestinal, topical, sublingual or rectal administration.
발명의 약학 조성물은 상술한 바와 같은 투여 경로에 따라 경구투여용 또는 비경구 투여용 제제로 제형화 할 수 있다. 제형화할 경우에는 하나 이상의 완충제(예를 들어, 식염수 또는 PBS), 항산화제, 정균제, 킬레이트화제(예를 들어, EDTA 또는 글루타치온), 충진제, 증량제, 결합제, 아쥬반트(예를 들어, 알루미늄 하이드록사이드), 현탁제, 농후제 습윤제, 붕해제 또는 계면활성제, 희석제 또는 부형제를 사용하여 조제될 수 있다.The pharmaceutical composition of the invention may be formulated into a formulation for oral administration or parenteral administration according to the route of administration as described above. When formulated, one or more buffers (e.g. saline or PBS), antioxidants, bacteriostatic agents, chelating agents (e.g. EDTA or glutathione), fillers, extenders, binders, adjuvants (e.g. aluminum hydroxide) Side), suspending agents, thickening humectants, disintegrants or surfactants, diluents or excipients.
경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 액제, 겔제, 시럽제, 슬러리제, 현탁액 또는 캡슐제 등이 포함되며, 이러한 고형제제는 본 발명의 약학 조성물에 적어도 하나 이상의 부형제 예를 들면, 전분(옥수수 전분, 밀 전분, 쌀 전분, 감자 전분 등 포함), 칼슘카보네이트(calcium carbonate), 수크로스(sucrose), 락토오스(lactose), 덱스트로오스, 솔비톨, 만니톨, 자일리톨, 에리스리톨 말티톨, 셀룰로즈, 메틸 셀룰로즈, 나트륨 카르복시메틸셀룰로오즈 및 하이드록시프로필메틸-셀룰로즈 또는 젤라틴 등을 섞어 조제될 수 있다. 예컨대, 활성성분을 고체 부형제와 배합한 다음 이를 분쇄하고 적합한 보조제를 첨가한 후 과립 혼합물로 가공함으로써 정제 또는 당의 정제를 수득할 수 있다.Solid form preparations for oral administration include tablets, pills, powders, granules, solutions, gels, syrups, slurries, suspensions or capsules, and the like, and the solid form may include at least one excipient in the pharmaceutical composition of the present invention, for example , Starch (including corn starch, wheat starch, rice starch, potato starch, etc.), calcium carbonate, sucrose, lactose, dextrose, sorbitol, mannitol, xylitol, erythritol maltitol, cellulose , Methyl cellulose, sodium carboxymethylcellulose and hydroxypropylmethyl-cellulose or gelatin may be prepared by mixing. For example, tablets or sugar tablets can be obtained by combining the active ingredient with a solid excipient and then grinding it, adding suitable auxiliaries and then processing the granule mixture.
단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제 또는 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물 또는 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제 또는 보존제 등이 포함될 수 있다.In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Liquid preparations for oral use include suspensions, solutions, emulsions, or syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, or preservatives, in addition to water or liquid paraffin, which are commonly used simple diluents. .
또한, 경우에 따라 가교결합 폴리비닐피롤리돈, 한천, 알긴산 또는 나트륨 알기네이트 등을 붕해제로 첨가할 수 있으며, 항응집제, 윤활제, 습윤제, 향료, 유화제 및 방부제 등을 추가로 포함할 수 있다.In addition, in some cases, crosslinked polyvinylpyrrolidone, agar, alginic acid or sodium alginate may be added as a disintegrant, and may further include an anticoagulant, a lubricant, a humectant, a perfume, an emulsifier, a preservative, and the like. .
비경구적으로 투여하는 경우 본 발명의 약학 조성물은 적합한 비경구용 담체와 함께 주사제, 경피 투여제 및 비강 흡입제의 형태로 당 업계에 공지된 방법에 따라 제형화될 수 있다. 상기 주사제의 경우에는 반드시 멸균되어야 하며 박테리아 및 진균과 같은 미생물의 오염으로부터 보호되어야 한다. 주사제의 경우 적합한 담체의 예로는 이에 한정되지는 않으나, 물, 에탄올, 폴리올(예를 들어, 글리세롤, 프로필렌 글리콜 및 액체 폴리에틸렌 글리콜 등), 이들의 혼합물 및/또는 식물유를 포함하는 용매 또는 분산매질일 수 있다. 보다 바람직하게는, 적합한 담체로는 행크스 용액, 링거 용액, 트리에탄올 아민이 함유된 PBS (phosphate buffered saline) 또는 주사용 멸균수, 10% 에탄올, 40% 프로필렌 글리콜 및 5% 덱스트로즈와 같은 등장 용액 등을 사용할 수 있다. 상기 주사제를 미생물 오염으로부터 보호하기 위해서는 파라벤, 클로로부탄올, 페놀, 소르빈산, 티메로살 등과 같은 다양한 항균제 및 항진균제를 추가로 포함할 수 있다. 또한, 상기 주사제는 대부분의 경우 당 또는 나트륨 클로라이드와 같은 등장화제를 추가로 포함할 수 있다.When administered parenterally, the pharmaceutical compositions of the present invention may be formulated according to methods known in the art in the form of injections, transdermal and nasal inhalants with suitable parenteral carriers. Such injections must be sterile and protected from contamination of microorganisms such as bacteria and fungi. Examples of suitable carriers for injections include, but are not limited to, solvents or dispersion media comprising water, ethanol, polyols (e.g., glycerol, propylene glycol and liquid polyethylene glycols, etc.), mixtures thereof and / or vegetable oils Can be. More preferably, suitable carriers include Hanks solution, Ringer's solution, phosphate buffered saline (PBS) containing triethanol amine or sterile water for injection, 10% ethanol, 40% propylene glycol and 5% dextrose Etc. can be used. In order to protect the injection from microbial contamination, various antibacterial and antifungal agents such as parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like may be further included. In addition, the injection may in most cases further comprise an isotonic agent such as sugar or sodium chloride.
경피 투여제의 경우 연고제, 크림제, 로션제, 겔제, 외용액제, 파스타제, 리니멘트제, 에어롤제 등의 형태가 포함된다. 상기에서 ‘경피 투여’는 약학 조성물을 국소적으로 피부에 투여하여 약학 조성물에 함유된 유효한 양의 활성 성분이 피부 내로 전달되는 것을 의미한다.In the case of transdermal administrations, ointments, creams, lotions, gels, external preparations, pasta preparations, linen preparations, air rolls and the like are included. As used herein, "transdermal administration" refers to the topical administration of the pharmaceutical composition to the skin to deliver an effective amount of the active ingredient contained in the pharmaceutical composition into the skin.
흡입 투여제의 경우, 본 발명에 따라 사용되는 화합물은 적합한 추진제, 예를 들면, 디클로로플루오로메탄, 트리클로로플루오로메탄, 디클로로테트라플루오로에탄, 이산화탄소 또는 다른 적합한 기체를 사용하여, 가압 팩 또는 연무기로부터 에어로졸 스프레이 형태로 편리하게 전달 할 수 있다. 가압 에어로졸의 경우, 투약 단위는 계량된 양을 전달하는 밸브를 제공하여 결정할 수 있다. 예를들면, 흡입기 또는 취입기에 사용되는 젤라틴 캡슐 및 카트리지는 화합물, 및 락토즈 또는 전분과 같은 적합한 분말 기제의 분말 혼합물을 함유하도록 제형화할 수 있다. 비경구 투여용 제형은 모든 제약 화학에 일반적으로 공지된 처방서인 문헌(Remington's Pharmaceutical Science, 15th Edition, 1975. Mack Publishing Company, Easton, Pennsylvania 18042, Chapter 87: Blaug, Seymour)에 기재되어 있다.In the case of inhaled dosages, the compounds used according to the invention may be pressurized packs or by means of suitable propellants, for example dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. It can be delivered conveniently from the nebulizer in the form of an aerosol spray. In the case of a pressurized aerosol, the dosage unit can be determined by providing a valve to deliver a metered amount. For example, gelatin capsules and cartridges for use in an inhaler or insufflator can be formulated to contain a mixture of the compound and a suitable powder base such as lactose or starch. Formulations for parenteral administration are described in Remington's Pharmaceutical Science, 15th Edition, 1975. Mack Publishing Company, Easton, Pennsylvania 18042, Chapter 87: Blaug, Seymour, a prescription generally known in all pharmaceutical chemistries.
본 발명의 근육 질환 예방 및 치료용 약학 조성물은 데칸알을 유효량으로 포함 할 때 바람직한 근육 질환 예방 및 치료 효과를 제공할 수 있다. 본 발명에서, "유효량"이라 함은 음성 대조군에 비해 그 이상의 반응을 나타내는 양을 말하며 바람직하게는 근 기능을 향상시키기에 충분한 양을 말한다. 본 발명의 약학 조성물에 데칸알이 0.01 내지 99.99% 포함될 수 있으며, 잔량은 약학적으로 허용 가능한 담체가 차지할 수 있다. 본 발명의 약학 조성물에 포함되는 데칸알의 유효량은 조성물이 제품화되는 형태 등에 따라 달라질 것이다.The pharmaceutical composition for preventing and treating muscle diseases of the present invention can provide a desirable muscle disease prevention and treatment effect when it contains an effective amount of decanal. In the present invention, the "effective amount" refers to an amount that exhibits a higher response than the negative control, and preferably an amount sufficient to improve muscle function. Deccanal may be included in the pharmaceutical composition of the present invention from 0.01 to 99.99%, the balance may be occupied by a pharmaceutically acceptable carrier. The effective amount of decanal included in the pharmaceutical composition of the present invention will vary depending on the form in which the composition is commercialized and the like.
본 발명의 약학 조성물의 총 유효량은 단일 투여량(single dose)으로 환자에게 투여될 수 있으며, 다중 투여량(multiple dose)으로 장기간 투여되는 분할 치료 방법(fractionated treatment protocol)에 의해 투여될 수 있다. 상술한 요소들은 모두 교려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다.The total effective amount of the pharmaceutical composition of the present invention may be administered to a patient in a single dose, and may be administered by a fractionated treatment protocol that is administered in multiple doses for a long time. It is important to administer all of the above factors in such a way that the maximum effect can be obtained in a minimum amount without side effects, which can be easily determined by those skilled in the art.
본 발명의 약학 조성물은 질환의 정도에 따라 유효성분의 함량을 달리할 수 있다. 비경구 투여시는 상기 데칸알을 기준으로 하루에 체중 1 kg당 바람직하게 0.01 내지 50 mg, 더 바람직하게는 0.1 내지 30 mg의 양으로 투여되도록, 그리고 경구 투여시는 데칸알을 기준으로 하루에 체중 1 kg당 바람직하게 0.01 내지 100 mg, 더 바람직하게는 0.01 내지 10 mg의 양으로 투여되도록 1 내지 수회에 나누어 투여할 수 있다. 그러나 상기 데칸알의 용량은 약학 조성물의 투여 경로 및 치료 횟수뿐만 아니라 환자의 연령, 체중, 건강 상태, 성별, 질환의 중증도, 식이 및 배설율 등 다양한 요인들을 고려하여 환자에 대한 유효 투여량이 결정되는 것이므로, 이러한 점을 고려할 때 당 분야의 통상적인 지식을 가진 자라면 상기 데칸알을 근육 질환 예방 및 치료를 위한 특정한 용도에 따른 적절한 유효 투여량을 결정할 수 있을 것이다. 본 발명에 따른 약학 조성물은 본 발명의 효과를 보이는 한 그 제형, 투여 경로 및 투여 방법에 특별히 제한되지 아니한다.The pharmaceutical composition of the present invention may vary the content of the active ingredient depending on the extent of the disease. Parenteral administration is preferably to be administered in an amount of preferably 0.01 to 50 mg, more preferably 0.1 to 30 mg per kg of body weight per day based on the decanal, and oral administration per day based on decanal It can be administered in one to several times to be administered in an amount of preferably 0.01 to 100 mg, more preferably 0.01 to 10 mg per kg body weight. However, the dose of decanal is determined in consideration of various factors such as the age, weight, health condition, sex, severity of the disease, diet and excretion rate, as well as the route and frequency of treatment of the pharmaceutical composition. In view of this, one of ordinary skill in the art will be able to determine the appropriate effective dosage of the decanal for a particular use for the prevention and treatment of muscle disease. The pharmaceutical composition according to the present invention is not particularly limited to its formulation, route of administration and method of administration as long as the effect of the present invention is shown.
본 발명의 근육 질환 예방 또는 치료용 약학 조성물은 단독으로, 또는 수술, 방사선 치료, 호르몬 치료, 화학 치료 또는 생물학적 반응조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The pharmaceutical composition for preventing or treating muscle diseases of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy or biological response modifiers.
본 발명의 근육 질환 예방 또는 치료용 약학 조성물은 또한 데칸알을 유효성분으로 포함하는 외용제의 제형으로 제공할 수 있다.The pharmaceutical composition for preventing or treating muscle diseases of the present invention may also be provided in the formulation of an external preparation containing decanal as an active ingredient.
본 발명의 근육 질환 예방 또는 치료용 약학 조성물을 피부외용제로 사용하는 경우, 추가로 지방 물질, 유기 용매, 용해제, 농축제 및 겔화제, 연화제, 항산화제, 현탁화제, 안정화제, 발포제(foaming agent), 방향제, 계면활성제, 물, 이온형 유화제, 비이온형 유화제, 충전제, 금속이온봉쇄제, 킬레이트화제, 보존제, 비타민, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 활성제, 친유성 활성제 또는 지질 소낭 등 피부 외용제에 통상적으로 사용되는 임의의 다른 성분과 같은 피부 과학 분야에서 통상적으로 사용되는 보조제를 함유할 수 있다. 또한 상기 성분들은 피부 과학 분야에서 일반적으로 사용되는 양으로 도입될 수 있다.When the pharmaceutical composition for preventing or treating muscle diseases of the present invention is used as an external preparation for skin, it is additionally used as a fatty substance, an organic solvent, a dissolving agent, a thickening agent and a gelling agent, an emollient, an antioxidant, a suspending agent, a stabilizer, and a foaming agent. ), Fragrance, surfactant, water, ionic emulsifier, nonionic emulsifier, filler, metal ion sequestrant, chelating agent, preservative, vitamin, blocking agent, wetting agent, essential oil, dye, pigment, hydrophilic active agent, lipophilic active agent Or any other ingredient commonly used in external preparations for skin, such as lipid vesicles. The ingredients may also be introduced in amounts generally used in the field of dermatology.
본 발명의 근육 질환 예방 또는 치료용 약학 조성물이 피부 외용제로 제공될 경우, 이에 제한되는 것은 아니나, 연고, 패취, 겔, 크림 또는 분무제 등의 제형일 수 있다.When the pharmaceutical composition for preventing or treating muscle diseases of the present invention is provided as an external preparation for skin, it may be a formulation such as, but not limited to, ointment, patch, gel, cream or spray.
또한, 본 발명은 하기 화학식 1로 표시되는 데칸알(Decanal) 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 질환 예방 또는 개선용 건강기능성 식품 조성물을 제공한다. 상기 데칸알의 구체적인 내용은 전술한 바와 같다. In addition, the present invention provides a decanal compound represented by the following formula (Decanal) compound or a pharmaceutically acceptable salt thereof as an active ingredient provides a health functional food composition for preventing or improving muscle diseases. Details of the decanal are as described above.
[화학식 1][Formula 1]
또한, 본 발명은 하기 화학식 1로 표시되는 데칸알(Decanal) 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 분화 촉진, 근육 재생 또는 근육 강화용 건강기능성 식품 조성물을 제공한다. 상기 데칸알의 구체적인 내용은 전술한 바와 같다. In addition, the present invention provides a health functional food composition for promoting muscle differentiation, muscle regeneration or muscle strengthening comprising a decanal compound represented by Formula 1 below or a pharmaceutically acceptable salt thereof as an active ingredient. Details of the decanal are as described above.
[화학식 1][Formula 1]
구체적으로, 본 발명의 일 실시예에 따르면, 데칸알을 첨가한 고지방식이를 섭취시킨 마우스에서, 사지근력이 유의적으로 증가하였으며, 상기 마우스의 근 섬유 직경이 유의적으로 증가하였음을 확인할 수 있었다. 즉, 본 발명의 데칸알은 근육을 강화시킴으로써, 마우스의 사지근력을 증가시키며, 고지방식이 섭취에 따른 근 손실 및 근력 약화를 개선할 수 있다. Specifically, according to an embodiment of the present invention, in the mice fed high fat diet containing decanal, the extremity muscle strength was significantly increased, it can be seen that the muscle fiber diameter of the mouse significantly increased. there was. That is, the decanal of the present invention can increase the extremity muscle strength of the mouse by strengthening the muscle, and can improve the muscle loss and muscle weakness according to the high fat diet.
본 발명의 식품 조성물은 기능성 식품(functional food), 영양 보조제(nutritional supplement), 건강식품(health food), 식품 첨가제(food additives) 및 사료 등의 모든 형태를 포함하며, 인간 또는 가축을 비롯한 동물을 취식대상으로 한다. 상기 유형의 식품 조성물은 당 업계에 공지된 통상적인 방법에 따라 다양한 형태로 제조할 수 있다.The food composition of the present invention includes all forms such as functional food, nutritional supplement, health food, food additives and feed, and includes animals such as humans or livestock. It is for eating. Food compositions of this type can be prepared in various forms according to conventional methods known in the art.
본 발명에 따른 식품 조성물은 당업계에 공지된 통상적인 방법에 따라 다양한 형태로 제조할 수 있다. 일반 식품으로는 이에 한정되지 않지만 음료(알콜성 음료 포함), 과실 및 그의 가공식품(예: 과일통조림, 병조림, 잼, 마아말레이드 등), 어류, 육류 및 그 가공식품(예: 햄, 소시지 콘비이프 등), 빵류 및 면류(예: 우동, 메밀국수, 라면, 스파게이트, 마카로니 등), 과즙, 각종 드링크, 쿠키, 엿, 유제품(예: 버터, 치이즈 등), 식용식물 유지, 마아가린, 식물성 단백질, 레토르트 식품, 냉동식품, 각종 조미료(예: 된장, 간장, 소스 등) 등에 본 발명의 데칸알을 첨가하여 제조할 수 있다. 또한, 영양보조제로는 이에 한정되지 않지만 캡슐, 타블렛, 환 등에 본 발명의 데칸알을 첨가하여 제조할 수 있다. 또한, 건강 기능식품으로는 이에 한정되지 않지만 예를 들면, 본 발명의 데칸알 자체를 차, 쥬스 및 드링크의 형태로 제조하여 음용(건강음료)할 수 있도록 액상화, 과립화, 캡슐화 및 분말화하여 섭취할 수 있다. 또한, 본 발명의 데칸알을 식품 첨가제의 형태로 사용하기 위해서는 분말 또는 농축액 형태로 제조하여 사용할 수 있다. 또한, 본 발명의 데칸알과 근육 질환 예방 및 근 기능 개선 효과가 있다고 알려진 공지의 활성 성분과 함께 혼합하여 조성물의 형태로 제조할 수 있다.The food composition according to the present invention can be prepared in various forms according to conventional methods known in the art. General foods include, but are not limited to, beverages (including alcoholic beverages), fruits and processed foods (e.g. canned fruit, canned foods, jams, marmalade, etc.), fish, meat and processed foods (e.g. hams, sausages) Cornbread, etc.), breads and noodles (e.g. udon, soba noodles, ramen, spagate, macaroni, etc.), fruit juices, various drinks, cookies, malts, dairy products (e.g. butter, cheese), edible vegetable oils, margarine It can be prepared by adding the decanal of the present invention to vegetable protein, retort food, frozen food, various seasonings (eg, miso, soy sauce, sauce, etc.). In addition, as a nutritional supplement is not limited to this can be prepared by adding the decanal of the present invention to capsules, tablets, pills, and the like. In addition, as a health functional food, but not limited to, for example, by making the decanal itself of the present invention in the form of tea, juice and drinks to be liquefied, granulated, encapsulated and powdered to drink (healthy drink) It can be ingested. In addition, in order to use the decanal of the present invention in the form of a food additive, it can be prepared in powder or concentrate form. In addition, it can be prepared in the form of a composition by mixing with the decanal of the present invention and known active ingredients known to be effective in preventing muscle diseases and improving muscle function.
본 발명의 데칸알을 건강음료로 이용하는 경우, 상기 건강음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드; 말토스, 슈크로스와 같은 디사카라이드; 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드; 자일리톨, 소르비톨, 에리트리톨 등의 당알콜일 수 있다. 감미제는 타우마틴, 스테비아 추출물과 같은 천연 감미제; 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 mL 당 일반적으로 약 0.01 ~ 0.04 g, 바람직하게는 약 0.02 ~ 0.03 g 이다.When the decanal of the present invention is used as a health beverage, the health beverage composition may contain various flavors or natural carbohydrates as additional components, as in general beverages. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Polysaccharides such as dextrin, cyclodextrin; Sugar alcohols such as xylitol, sorbitol, and erythritol. Sweeteners include natural sweeteners such as taumartin, stevia extract; Synthetic sweeteners such as saccharin and aspartame; The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the composition of the present invention.
또한, 본 발명의 데칸알은 근육 질환 예방 및 근 기능 개선용 식품 조성물의 유효성분으로 함유될 수 있는데, 그 양은 근육 질환 예방 및 근 기능 개선용 작용을 달성하기에 유효한 양으로 특별히 한정되는 것은 아니나, 전체 조성 물 총 중량에 대하여 0.01 내지 100 중량%인 것이 바람직하다. 본 발명의 식품 조성물은 데칸알과 함께 근육 질환 예방 및 근 기능 개선용 조성물에 효과가 있는 것으로 알려진 다른 활성 성분과 함께 혼합하여 제조될 수 있다.In addition, the decanal of the present invention may be contained as an active ingredient of the food composition for preventing muscle diseases and improving muscle function, the amount is not particularly limited to an amount effective to achieve the action for preventing muscle diseases and improving muscle function. It is preferably from 0.01 to 100% by weight relative to the total weight of the total composition. The food composition of the present invention may be prepared by mixing with decanal together with other active ingredients known to be effective in the composition for preventing muscle diseases and improving muscle function.
상기 외에 본 발명의 건강식품은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산, 펙트산의 염, 알긴산, 알긴산의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올 또는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 건강식품은 천연 과일주스, 과일주스 음료, 또는 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 혼합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부당 0.01 ~ 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the health food of the present invention is various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, Glycerin, alcohol or carbonation agent, and the like. In addition, the health food of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage, or vegetable beverage. These components can be used independently or in combination. The proportion of such additives is not critical but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
또한, 본 발명은 하기 화학식 1로 표시되는 데칸알(Decanal) 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근기능 개선용 화장료 조성물을 제공한다. 상기 데칸알의 구체적인 내용은 전술한 바와 같다. In addition, the present invention provides a cosmetic composition for improving muscle function comprising a decanal compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient. Details of the decanal are as described above.
[화학식 1][Formula 1]
상기 화장료 조성물은 특히 제한되는 것은 아니나, 피부 외용으로 사용하거나, 경구 섭취할 수 있다.The cosmetic composition is not particularly limited, but may be used externally or ingested orally.
본 발명의 화장료 조성물은 데칸알을 유효성분으로 함유하며 피부학적으로 허용 가능한 부형제와 함께 기초 화장품 조성물(화장수, 크림, 에센스, 클렌징 폼 및 클렌징 워터와 같은 세안제, 팩, 보디오일), 색조 화장품 조성물(화운데이션, 립스틱, 마스카라, 메이크업 베이스), 두발 제품 조성물(샴푸, 린스, 헤어컨디셔너, 헤어젤) 및 비누 등의 형태로 제조될 수 있다.The cosmetic composition of the present invention contains a decanal as an active ingredient and, together with a dermatologically acceptable excipient, a basic cosmetic composition (cleanser such as cosmetic water, cream, essence, cleansing foam and cleansing water, pack, body oil), color cosmetic composition (Foundation, lipstick, mascara, makeup base), hair product composition (shampoo, rinse, hair conditioner, hair gel) and soap and the like.
상기 부형제로는 이에 한정되지는 않으나 예를 들어, 피부연화제, 피부 침투 증강제, 착색제, 방향제, 유화제, 농화제 및 용매를 포함할 수 있다. 또한, 향료, 색소, 살균제, 산화방지제, 방부제 및 보습제 등을 추가로 포함할 수 있으며, 물성개선을 목적으로 점증제, 무기염류, 합성 고분자 물질 등을 포함할 수 있다. 예를 들면, 본 발명의 화장료 조성물로 세안제 및 비누를 제조하는 경우에는 통상의 세안제 및 비누 베이스에 상기 데칸알을 첨가하여 용이하게 제조할 수 있다. 크림을 제조하는 경우에는 일반적인 수중유적형(O/W)의 크림베이스에 데칸알 또는 이의 염을 첨가하여 제조할 수 있다. 여기에 향료, 킬레이트제, 색소, 산화방지제, 방부제 등과 물성개선을 목적으로 한 단백질, 미네랄, 비타민 등 합성 또는 천연소재를 추가로 첨가할 수 있다.The excipients include, but are not limited to, emollients, skin penetration enhancers, colorants, fragrances, emulsifiers, thickeners and solvents. In addition, fragrances, pigments, fungicides, antioxidants, preservatives and moisturizing agents may be further included, and may include thickeners, inorganic salts, synthetic polymer materials and the like for the purpose of improving the properties. For example, when the face wash and the soap are manufactured with the cosmetic composition of the present invention, the decanal may be easily added to the face wash and the soap base. In the case of preparing the cream, it may be prepared by adding decanal or a salt thereof to a cream base of a general oil-in-water type (O / W). To this, synthetic or natural materials, such as proteins, minerals, vitamins, etc., for the purpose of improving physical properties, such as flavors, chelating agents, pigments, antioxidants, and preservatives, may be added.
본 발명의 화장료 조성물에 함유되는 데칸알의 함량은 이에 한정되지 않지만 전체 조성물 총중량에 대하여 0.001 내지 10 중량%인 것이 바람직하고, 0.01 내지 5중량%인 것이 더욱 바람직하다. 상기 함량이 0.001중량% 미만에서는 목적하는 항노화 또는 주름개선 효과를 기대할 수 없고, 10중량% 초과에서는 안전성 또는 제형상의 제조에 어려움이 있을 수 있다.The content of decanal contained in the cosmetic composition of the present invention is not limited thereto, but is preferably 0.001 to 10% by weight, more preferably 0.01 to 5% by weight based on the total weight of the composition. If the content is less than 0.001% by weight, the desired anti-aging or anti-wrinkle effect may not be expected, and when the content is more than 10% by weight, there may be difficulty in preparing a safety or formulation.
또한, 본 발명은 하기 화학식 1로 표시되는 데칸알(Decanal)화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 질환 예방 또는 치료용 가축사료용 조성물을 제공한다. 상기 데칸알의 구체적인 내용은 전술한 바와 같다. In addition, the present invention provides a composition for animal feed for preventing or treating muscle diseases, comprising a decanal compound represented by Formula 1 below or a pharmaceutically acceptable salt thereof as an active ingredient. Details of the decanal are as described above.
[화학식 1][Formula 1]
상기 사료용 조성물은 사료 첨가제를 포함할 수 있다. 본 발명의 사료첨가제는 사료관리법상의 보조사료에 해당한다.The feed composition may include a feed additive. The feed additive of the present invention corresponds to a feed supplement in the Feed Control Act.
본 발명에서 용어, "사료"는 동물이 먹고, 섭취하며, 소화시키기 위한 또는 이에 적당한 임의의 천연 또는 인공 규정식, 한끼식 등 또는 상기 한끼식의 성분을 의미할 수 있다.As used herein, the term "feed" may refer to any natural or artificial diet, one meal, or the like, or a component of the one meal, for the animal to eat, ingest, and digest.
상기 사료의 종류는 특별히 제한되지 아니하며, 당해 기술 분야에서 통상적으로 사용되는 사료를 사용할 수 있다. 상기 사료의 비제한적인 예로는, 곡물류, 근과류, 식품 가공 부산물류, 조류, 섬유질류, 제약 부산물류, 유지류, 전분류, 박류 또는 곡물 부산물류 등과 같은 식물성 사료; 단백질류, 무기물류, 유지류, 광물성류, 유지류, 단세포 단백질류, 동물성 플랑크톤류 또는 음식물 등과 같은 동물성 사료를 들 수 있다. 이들은 단독으로 사용되거나 2 종 이상을 혼합하여 사용될 수 있다.The kind of the feed is not particularly limited, and may be used a feed commonly used in the art. Non-limiting examples of the feed may include plant feeds such as cereals, fruits, food processing by-products, algae, fibres, pharmaceutical by-products, oils, starches, gourds or grain by-products; And animal feeds such as proteins, minerals, fats and oils, minerals, fats and oils, single cell proteins, zooplankton or foods. These may be used alone or in combination of two or more thereof.
또한 상기 사료첨가제는 추가적으로 단위동물에 허용되는 담체를 함유할 수 있다. 본 발명에 있어서는 상기 사료첨가제를 그대로 또는 공지의 담체, 안정제 등을 가할 수 있으며, 필요에 따라 비타민, 아미노산류, 미네랄 등의 각종 양분, 항산화제 및 기타의 첨가제 등을 가할 수도 있으며, 그 형상으로서는 분체, 과립, 펠릿, 현탁액 등의 적당한 상태일 수 있다. 본 발명의 사료첨가제를 공급하는 경우는 단위동물에 대하여 단독으로 또는 사료에 혼합하여 공급할 수 있다.In addition, the feed additive may additionally contain a carrier that is acceptable to the unit animal. In the present invention, the feed additive may be added as it is, or a known carrier, stabilizer, or the like. If necessary, various nutrients such as vitamins, amino acids, minerals, antioxidants, and other additives may be added. Powders, granules, pellets, suspensions and the like may be in a suitable state. In the case of supplying the feed additive of the present invention, the unit animal may be supplied alone or mixed with feed.
이하, 본 발명을 실시예에 의해 상세히 설명하기로 한다. 그러나 이들 실시예는 본 발명을 보다 구체적으로 설명하기 위한 것으로서, 본 발명의 범위가 이들 실시예에 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail by way of examples. However, these examples are intended to illustrate the present invention in more detail, and the scope of the present invention is not limited to these examples.
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실시예Example
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실시예Example
1. One.
마우스근아세포를Mouse myoblasts
이용한 Used
데칸알의Decanal
근손실억제Muscle loss suppression
효능 efficacy
1-1. 1-1.
MyotubeMyotube
두께 변화 확인 Check thickness change
(1) 세포배양(1) Cell culture
마우스근아세포(mouse myoblast cell line, C2C12 cell)를 ATCC사(Manassas, VA, USA)로부터 구매하여 사용하였다. 구입한 세포를 10% feta bovine serum(FBS) media를 이용하여 37, 5% CO2 인큐베이터에서 배양하여 실험에 사용하였다. 세포가 80% confluent해지면 2% Horse serum(HS) media를 이용하여 myotube로 분화시켰다. 분화 4일 째 되는 날부터 이틀 간 dexamethasone (50 μM)과 데칸알(100 μM)을 함께 처리하였다.Mouse myoblast cell lines (C2C12 cells) were purchased from ATCC (Manassas, VA, USA) and used. The purchased cells were incubated in 37, 5% CO 2 incubator using 10% feta bovine serum (FBS) media and used in the experiment. When the cells became 80% confluent, they were differentiated into myotubes using 2% Horse serum (HS) media. Two days from the 4 th day of differentiation, dexamethasone (50 μM) and decanal (100 μM) were treated together.
(2) Giemsa-wright staining(2) Giemsa-wright staining
Phosphate buffered saline(PBS)으로 세포를 2회 세척한 후 100% methanol으로 10분동안 고정하였다. 고정이 완료되면 상온에서 10분간 자연건조시킨 후 myotube를 특이적으로 염색시키는 Giemsa-wright staining solution(서울, 아산제약)을 떨어뜨려 30분간 염색하였다.The cells were washed twice with Phosphate buffered saline (PBS) and fixed for 10 minutes with 100% methanol. When the fixation was completed, the resultant was dried for 10 minutes at room temperature, and then stained for 30 minutes by dropping Giemsa-wright staining solution (Seoul, Asan Pharmaceutical) that specifically stained myotubes.
(3) Myotube 두께 측정(3) Myotube thickness measurement
염색된 myotube는 형광현미경(IX 71, Olympus)을 이용하여 X20 배율로 촬영 후 image J software(USA)를 이용하여 분석되었다. 각 well에서 6 부분을 무작위로 선택하여 현미경 촬영하였으며, 각 well로부터 최소 100개의 myotube 두께를 분석하였다(3회 반복/Group). Stained myotubes were photographed at X20 magnification using a fluorescence microscope (IX 71, Olympus) and analyzed using image J software (USA). Six sections of each well were randomly selected and micrographed, and at least 100 myotube thicknesses were analyzed from each well (3 replicates / Group).
그 결과, 대조세포(Dexa)에서는 정상세포(Basal)에 비해 myotube의 두께가 현저히 감소하였으며, 데칸알 처리는 dexamethasone에 의해 감소한 myotube 두께를 다시 증가시키는 것을 시각적으로 확인할 수 있었다(도 1a). 이를 image J software를 이용하여 수치화한 결과에서도 데칸알 처리는 dexamethasone에 의해 유의적으로 감소한 myotube 두께를 다시 74% 증가시켰다(도 1b). 따라서 데칸알은 마우스근아세포에서 myotube의 두께를 증가시켜 근손실을 억제하고, 근성장을 촉진시키는 것을 알 수 있다.As a result, the thickness of myotube was significantly reduced in control cells (Dexa) compared to normal cells (Basal), and decanal treatment was visually confirmed to increase the thickness of myotube reduced by dexamethasone again (FIG. 1A). Deccanal treatment also increased 74% of myotube thickness, which was significantly reduced by dexamethasone, even after quantification using image J software (FIG. 1B). Therefore, decanal increases the thickness of myotube in mouse myoblasts, inhibits muscle loss and promotes muscle growth.
실시예Example
2. 작용기작 규명 2. Identify the mechanism of action
2-1. 2-1.
TrizolTrizol
method를 이용한 RNA 분리 및 RT- RNA separation and RT- using method
PCRPCR
(reverse transcription-polymerase chain reaction) (reverse transcription-polymerase chain reaction)
마우스근아세포 1*107 cells 당 Trizol 용액 334 ㎕을 첨가하여 갈아준 후, 4, 12,000 xg에서 10분간 원심분리하였다. 상층액을 새 튜브로 옮긴 후 chloroform 67 ㎕을 첨가하고, 세게 흔들어주었다. 다시 상층액을 새 튜브로 옮기고 상층액과 isopropanol의 비율이 1:1이 되도록 isopropanol을 첨가하였다. 10회 세게 흔든 다음 실온에서 15분 동안 방치하고, 12,000 xg, 4에서 10분간 원심분리 시킨 후 상층액을 제거하고, 남은 침전물에 70% ethanol 1 ml을 가한 후 7,500 xg, 4에서 5분 동안 원심분리 하였다. 에탄올을 제거한 후 RNA 침전물이 담긴 튜브를 실온에서 15분 동안 건조시키고, nuclease free water를 사용하여 RNA pellet을 용해시켰다. UV/VIS spectrophotometer(Beckman coulter, DU730)를 이용하여 260 nm 및 280 nm 파장에서 추출된 RNA 시료의 농도를 측정하고, agarose gel electrophoresis를 실시하여 RNA 시료의 integrity를 확인하였다.334 μl of Trizol solution was added per 1 * 107 cells of mouse myoblasts, and then centrifuged at 4, 12,000 xg for 10 minutes. After transferring the supernatant to a new tube, 67 μl of chloroform was added and shaken vigorously. Again, the supernatant was transferred to a new tube and isopropanol was added so that the ratio of the supernatant to isopropanol was 1: 1. Shake vigorously 10 times and leave at room temperature for 15 minutes, centrifuge at 12,000 xg, 4 minutes for 10 minutes, remove supernatant, add 1 ml of 70% ethanol to the remaining precipitate, and centrifuge at 7,500 xg, 4 minutes for 5 minutes. Separated. After removing ethanol, the tube containing the RNA precipitate was dried at room temperature for 15 minutes, and the RNA pellet was dissolved using nuclease free water. Using a UV / VIS spectrophotometer (Beckman coulter, DU730) was measured the concentration of RNA samples extracted at 260 nm and 280 nm wavelength, and the integrity of the RNA samples were confirmed by agarose gel electrophoresis.
마우스근아세포에서 추출된 RNA시료를 대상으로 oligo dT primer와 superscript reverse transcriptase (GIBCO BRL, Gaithersburg, MD, USA)을 이용하여 reverse transcription을 수행함으로써 cDNA를 합성하였다. Reverse transcription을 통해 얻은 cDNA를 template로 하고 증폭하고자 하는 유전자 cDNA의 5'과 3' flanking sequence를 primer로 사용하여 PCR을 수행하였으며, 이때 사용된 primer sequence를 [표 1]에 나타냈다. 증폭된 PCR 산물 1 ㎕를 1% agarose gel에 전기영동하여 DNA band를 확인하였다.RNA samples extracted from mouse myoblasts were synthesized by reverse transcription using oligo dT primer and superscript reverse transcriptase (GIBCO BRL, Gaithersburg, MD, USA). PCR was performed using 5 'and 3' flanking sequences of the gene cDNA to be amplified as a template and cDNA obtained through reverse transcription. The primer sequences used are shown in [Table 1]. 1 μl of the amplified PCR product was electrophoresed on 1% agarose gel to confirm DNA bands.
유전자gene | 프라이머primer | 염기서열 (5’→3')Sequence (5 '→ 3') | 어닐링Annealing 온도(℃) Temperature (℃) | PCRPCR 산물 (bp) Product (bp) |
MaFbx(synonym: atrogin-1)MaFbx (synonym: atrogin-1) | FF | GTCCAGAGAGTCGGCAAGTCGTCCAGAGAGTCGGCAAGTC | 6363 | 141141 |
RR | GTCGGTGATCGTGAGACCTTGTCGGTGATCGTGAGACCTT | |||
MuRF1(synonym: TRAM63)MuRF1 (synonym: TRAM63) | FF | ACATCTACTGTCTCACGTGT ACATCTACTGTCTCACGTGT | 5858 | 106106 |
RR | TGTCCTTGGAAGATGCTTTGTGTCCTTGGAAGATGCTTTG | |||
Glyceraldehyde 3-phosphate dehydrogenase (GAPDH)Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) | FF | GTGATGGCATGGACTGTGGTGTGATGGCATGGACTGTGGT | 5555 | 163163 |
RR | GGAGCCAAAAGGGTCATCATGGAGCCAAAAGGGTCATCAT |
2-2. Western blotting2-2. Western blotting
세포에서 western blotting을 수행하기 위해 media를 제거한 각 well에 500 μL의 100 mM Tris-HCl, pH 7.4, 5 mM EDTA, 50 mM sodium pyrophosphate, 50 mM NaF, 100 mM orthovanadate, 1% Triton X-100, 1 mM phenylmethanesulfonyl fluoride, 2 ㎍/mL aprotinin, 1 ㎍/mL pepstatin A, and 1 ㎍/mL leupeptin을 포함하는 lysis buffer를 넣고 harvest한 후 1,300 x g, 4에서 20분간 원심분리한 후 가운데 층을 취하고 Bradford 법에 따라 단백질을 정량하였다(Bio-Rad). 단백질 40 ㎍을 SDS polyacrylamide gel에 전기영동시킨 후 nitrocellulose membranes (Amersham, Buckinghamshire, UK)으로 이동시켰다. Membrane을 tris-buffered saline과 tween 20 용액(TBS-T)을 이용하여 10분 동안 3회 반복하여 세척한 후 10% skim milk를 이용하여 60분간 차단하였다. Membrane을 1:1,000의 비율로 희석한 1차 항체에 넣어 4°C에서 부드럽게 흔들어 12시간 동안 배양한 후 TBS-T를 이용하여 세척하였고, membrane을 다시 1:2,000의 비율로 희석한 2차 항체와 함께 60분 동안 배양하고 세척하였다. 이 때, 1차 항체는 Foxo, phospho-foxo(p-foxo), S6K1, phopho-S6K1(p-S6K1), 4EB-P1, phospho-4EBP-1 그리고 GAPDH (Cell Signaling Technology, Beverly, MA, USA)를 사용하였다. 최종적으로 단백질을 X-ray 필름에 ECL Western blot detection kit (RPN2106, Amersham, Arlington Heights, IL, USA)를 사용하여 시각화하였다. X-ray 필름에 시각화된 밴드를 스캔 후 Quantity One analysis software (Bio-Rad)를 이용하여 정량화하였다.500 μL of 100 mM Tris-HCl, pH 7.4, 5 mM EDTA, 50 mM sodium pyrophosphate, 50 mM NaF, 100 mM orthovanadate, 1% Triton X-100, in each well from which media was removed to perform western blotting in cells Add and harvest lysis buffer containing 1 mM phenylmethanesulfonyl fluoride, 2 μg / mL aprotinin, 1 μg / mL pepstatin A, and 1 μg / mL leupeptin, harvest, centrifuge at 1,300 xg, 4 min for 20 min Proteins were quantified according to the method (Bio-Rad). 40 μg of protein was electrophoresed on SDS polyacrylamide gel and then transferred to nitrocellulose membranes (Amersham, Buckinghamshire, UK). Membrane was washed three times for 10 minutes using tris-buffered saline and tween 20 solution (TBS-T) and then blocked for 60 minutes using 10% skim milk. Membrane was added to the primary antibody diluted at a ratio of 1: 1,000, shaked gently at 4 ° C, incubated for 12 hours, washed with TBS-T, and the membrane was again diluted at a ratio of 1: 2,000. Incubated for 60 minutes and washed. At this time, the primary antibody is Foxo, phospho-foxo (p-foxo), S6K1, phopho-S6K1 (p-S6K1), 4EB-P1, phospho-4EBP-1 and GAPDH (Cell Signaling Technology, Beverly, MA, USA ) Was used. Finally, the proteins were visualized on an X-ray film using an ECL Western blot detection kit (RPN2106, Amersham, Arlington Heights, IL, USA). Bands visualized on the X-ray film were scanned and quantified using Quantity One analysis software (Bio-Rad).
그 결과, 대조세포(Dexa)에서는 정상세포(Basal)에 비해 단백질 합성과 관련이 있는 p-4EBP1 및 p-p70S6K1 단백질 양이 유의적으로 감소한 반면, 단백질 분해 유전자인 MaFbx/atrogin1과 MuRF1 발현은 유의적으로 증가하였다. 데칸알 처리는 dexamethasone에 의해 감소한 p-4EBP1 및 p-p70S6K 단백질 양을 다시 유의적으로 증가시키는 한편, MuRF1 및 MaFbx/atrogin1의 발현은 유의하게 감소시켰다[그림 2]. 따라서 데칸알은 마우스근아세포에서 4E-BP1 및 p70S6K1 단백질 인산화를 증가시키고, MuRF1 및 MaFbx/atrogin1 유전자 발현을 억제함으로써 궁극적으로 근육의 양을 증가시키는데 관여하였을 것으로 사료된다.As a result, the amount of p-4EBP1 and p-p70S6K1 proteins related to protein synthesis was significantly decreased in control cells (Dexa), whereas the expression of MaFbx / atrogin1 and MuRF1, which are proteolytic genes, were significantly decreased. Increased by. Deccanal treatment significantly increased the amount of p-4EBP1 and p-p70S6K proteins reduced by dexamethasone, while significantly reducing the expression of MuRF1 and MaFbx / atrogin1 [Figure 2]. Therefore, decanal may be involved in ultimately increasing muscle mass by increasing 4E-BP1 and p70S6K1 protein phosphorylation in mouse myoblasts and suppressing MuRF1 and MaFbx / atrogin1 gene expression.
실시예Example
3. 마우스 근력테스트 3. Mouse strength test
3-1. 실험식이 제조 및 실험동물의 사육3-1. Experimental diet preparation and breeding of laboratory animals
5주령의 수컷 C57BL/6N 마우스 24마리(mating, 한국)를 상업적인 정상식이(rodant chow)로 1주일 간 실험실환경에 적응시킨 후, 난괴법에 따라 세 개의 군(Chow군, HFD군, Decanal군)으로 임의 배치하여 10주간 사육하였다. 본 실험에서 사용한 비만유도식이는 고지방대조식이(high fat diet, HFD: 40% fat calorie, 17 g lard + 3% corn oil/ 100 g diet)이며, 데칸알이 보충된 식이(decanal-supplemented high fat diet, Decanal)는 HFD와 조성이 동일하되 데칸알이 0.2% 수준으로 포함되도록 제조하였다. 정상식이군(Chow)은 상업적인 rodent chow를 섭취시켰다. 데칸알은 씨그마-알드리치 사에서 구입하였다. 실험식이 조성표는 하기 표 2에 나타낸 바와 같다. Twenty five-week-old male C57BL / 6N mice (mating, Korea) were adapted to a laboratory environment for one week as a commercial rodant chow, and then three groups (Chow, HFD, and Decanal) according to the ingot method. ) Were randomly placed and bred for 10 weeks. The obesity induction diet used in this study was a high fat diet (HFD: 40% fat calorie, 17 g lard + 3% corn oil / 100 g diet) and was supplemented with decanal supplement (decanal-supplemented high). fat diet, Decanal) was prepared to have the same composition as HFD but contained 0.2% decanal. Chow fed a commercial rodent chow. Deccanal was purchased from Sigma-Aldrich. The experimental dietary table is shown in Table 2 below.
성분ingredient | 고지방대조식이High fat control diet (( HFDHFD )) (g/kg diet)(g / kg diet) | 데칸알Decanal 보충식이Supplementary diet (( DecanalDecanal )) (g/kg diet)(g / kg diet) |
카제인 |
200200 | 200200 |
DL-메티오닌DL- |
33 | 33 |
옥수수 전분Corn starch | 111111 | 107107 |
수크로오스Sucrose | 370370 | 370370 |
셀룰로오스cellulose | 5050 | 5050 |
옥수수유Corn oil | 3030 | 3030 |
라아드 |
170170 | 170170 |
비타민 복합물Vitamin complex | 1212 | 1212 |
미네랄 복합물Mineral complex | 4242 | 4242 |
콜린 비타르트레이트Choline Bitartrate | 22 | 22 |
콜레스테롤 |
1010 | 1010 |
tert-부티하이드로퀴논tert-butyhydroquinone | 0.040.04 | 0.040.04 |
데칸알Decanal | -- | 22 |
총합(g)Total (g) | 1,0001,000 | 1,0001,000 |
지방(% 칼로리)Fat (% calories) | 39.039.0 | 39.039.0 |
총 열량, kJ/kg dietTotal calories, kJ / kg diet | 19,31519,315 | 19,31519,315 |
3-2) 3-2)
데칸알Decanal
섭취에 의한 마우스의 Of mouse by ingestion
사지근력Limb strength
증가 increase
데칸알 섭취에 의한 마우스 사지근력 변화를 확인하기 위하여 회전케이지 뚜껑에 마우스가 매달리는 시간을 측정하였다. In order to confirm the change in the extremity muscle of the mouse caused by the decanal intake, the time of hanging the mouse on the rotation cage cap was measured.
그 결과, 도 3에 나타난 바와 같이, 고지방식이를 10주간 섭취시킨 결과 Chow군에 비해 매달리는 시간(latency to fall)(도 3a) 및 매달리는 시간을 체중으로 보정해 준 값(holding impulse)(도 3b)이 모두 유의적으로 증가하였음을 확인할 수 있었다. 한편, 데칸알을 섭취시킨 군의 경우 매달리는 시간(latency to fall)(도 3a) 및 매달리는 시간을 체중으로 보정해 준 값(holding impulse)(도 3b)이 모두 고지방식이 대조군에 비해 각기 157% 및 159% 유의적으로 증가하였음을 확인할 수 있었다. As a result, as shown in Figure 3, the result of ingesting the high-fat diet for 10 weeks, compared to the Chow group, the hanging time (latency to fall) (holding impulse) (weight 3) All of 3b) was significantly increased. On the other hand, in the case of decanal intake group (latency to fall) (holding impulse) (latency to fall) (FIG. And 159% significantly increased.
3-3) 근육조직의 면역조직화학적 염색3-3) Immunohistochemical staining of muscle tissue
마우스의 근육 조직을 적출하고 10% 포르말린에 고정한 다음, hematoxylin and eosin(H&E) 염색을 한 후 광학현미경 (IX71, Olympus, JPN)을 이용하여 관찰하였다. 디지털 카메라 (DP71, Olympus, JPN)를 이용하여 사진을 촬영하고 이미지 제이 프로그램을 이용하여 근섬유 직경을 측정하였다.Muscle tissues of the mice were extracted and fixed in 10% formalin, and then stained with hematoxylin and eosin (H & E) and observed using an optical microscope (IX71, Olympus, JPN). Photos were taken using a digital camera (DP71, Olympus, JPN) and muscle fiber diameters were measured using an image Jay program.
그 결과, 도 4에 나타난 바와 같이, Rectus femoris(도 4a), soleus(도 4b), gastrocnemius(도 4c) 근육 모두에서 고지방식이 섭취에 의해 Chow 섭취 시보다 근섬유 직경이 유의하게 감소하였으며, 데칸알을 섭취시킨 마우스의 경우 고지방식이 대조군에 비해 근섬유 직경이 유의적으로 증가한 것을 확인할 수 있었다. 즉, 데칸알은 고지방식이를 섭취하는 마우스의 근 손실 및 근력 약화를 개선하는 효과가 매우 탁월함을 알 수 있다. As a result, as shown in Figure 4, the muscle fiber diameter of the Rectus femoris (FIG. 4A), soleus (FIG. 4B), gastrocnemius (FIG. 4C) muscle significantly reduced the intake of Chow than the intake of Chow, decane In the case of mice fed the eggs, the high fat diet was significantly increased compared to the control group. In other words, decanal can be seen that the effect of improving the muscle loss and muscle weakness of mice fed a high-fat diet is very excellent.
3-4) 통계분석3-4) Statistical Analysis
모든 자료의 통계분석은 statistical package for the social sciences(SPSS version 21.0, IBM, Armonk, NY, USA) PC package를 사용하여 실시하였고, 분석수치는 mean±SEM으로 나타내었다. 군간 유의적인 차이는 ANOVA를 실시하여 검증하였다. Statistical analysis of all data was performed using the statistical package for the social sciences (SPSS version 21.0, IBM, Armonk, NY, USA) PC package. Significant differences between groups were verified by ANOVA.
하기에 본 발명의 추출물을 함유하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, a preparation example of a composition containing an extract of the present invention will be described, but the present invention is not intended to be limited thereto but only to be described in detail.
제제예 1: 산제의 제조Formulation Example 1 Preparation of Powder
데칸알 20 ㎎Decanal 20 mg
유당수화물 100 ㎎ Lactose Carb 100 mg
탈크 10 ㎎ Talc 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조하였다.The above ingredients were mixed and filled in an airtight cloth to prepare a powder.
제제예 2: 정제의 제조Formulation Example 2: Preparation of Tablet
데칸알 10 ㎎Decanal 10 mg
옥수수전분 100 ㎎ Corn starch 100 mg
유당수화물 100 ㎎ Lactose Carb 100 mg
스테아르산마그네슘 2 ㎎Magnesium stearate 2mg
상기의 성분을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.
제제예 3: 캅셀제의 제조Formulation Example 3: Preparation of Capsule
데칸알 10 ㎎Decanal 10 mg
미결정셀룰로오스 3 ㎎ 3 mg of microcrystalline cellulose
유당수화물 14.8 ㎎Lactose carb 14.8 mg
스테아르산마그네슘 0.2 ㎎Magnesium Stearate 0.2 mg
상기의 성분을 혼합한 후, 통상의 캅셀제의 제조방법에 다라서 젤라틴캡슐에 충전하여 캅셀제를 제조하였다.After mixing the above components, it was filled in gelatin capsules according to the conventional method for producing a capsule to prepare a capsule.
제제예 4: 주사제의 제조Formulation Example 4 Preparation of Injection
데칸알 10 ㎎Decanal 10 mg
만니톨 180 ㎎ Mannitol 180 mg
주사용 멸균 증류수 2974 ㎎Sterile distilled water for injection 2974 mg
인산일수소나트퓸 26 ㎎Monohydrogen phosphate 26 mg
상기의 성분을 혼합한 후, 통상의 주사제의 제조방법에 따라 1앰플당(2mL) 상기의 성분 함량으로 제조하였다.After mixing the above components, it was prepared in the above ingredient content per ampoules (2 mL) according to the conventional method for preparing injections.
제제예 5: 액제의 제조Formulation Example 5 Preparation of Liquid
데칸알 10 ㎎Decanal 10 mg
이성화당 10 ㎎ Isomerized sugar 10 mg
만니톨 5 ㎎Mannitol 5 mg
정제수 적량Purified water
레몬향 적량Lemon flavor
상기의 성분을 통상의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 정제수를 가하여 전체 100mL로 조절한 후 멸균시켜 갈색병에 충진하여 액제를 제조한다. The above components are dissolved in purified water according to a conventional preparation method, dissolved in purified water, and then lemon juice is added in an appropriate amount. After adjusting to 100 mL in total, sterilized and filled in a brown bottle to prepare a liquid formulation.
제제예 6: 건강기능식품의 제조Formulation Example 6 Preparation of Health Functional Food
데칸알 10 ㎎Decanal 10 mg
비타민 혼합물 적량Vitamin mixture proper amount
비타민 A 아세테이드 70 ㎍70 μg of Vitamin A Acetate
비타민 E 1.0 ㎎Vitamin E 1.0 mg
비타민 B1 0.13 ㎎Vitamin B 1 0.13 mg
비타민 B2 0.15 ㎎Vitamin B 2 0.15 mg
비타민 B6 0.5 ㎎Vitamin B 6 0.5 mg
비타민 B12 0.2 ㎍0.2 μg of vitamin B 12
비타민 C 10 ㎎ Vitamin C 10 mg
비오틴 10 ㎍10 μg biotin
니코틴산아미드 1.7 ㎎Nicotinic Acid 1.7 mg
엽산 50 ㎍Folate 50 ㎍
판토텐산 칼슘 0.5 ㎎Calcium Pantothenate 0.5mg
무기질 혼합물 적량Mineral mixture
황산제1철 1.75 ㎎Ferrous Sulfate 1.75 mg
산화아연 0.82 ㎎Zinc Oxide 0.82 mg
탄산마그네슘 25.3 ㎎Magnesium carbonate 25.3 mg
제1인산칼륨 15 ㎎Potassium monophosphate 15 mg
제2인산칼슘 55 ㎎Dibasic calcium phosphate 55 mg
구연산칼륨 30 ㎎Potassium citrate 30 mg
탄산칼슘 100 ㎎ Calcium Carbonate 100 mg
염화마그네슘 24.8 ㎎Magnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method. The granules may be prepared and used for preparing a health food composition according to a conventional method.
제제예 7: 건강음료의 제조Formulation Example 7 Preparation of Health Beverage
데칸알 10 mgDecanal 10 mg
비타민 C 15 g15 g of vitamin C
비타민 E(분말) 100 g100 g of vitamin E (powder)
젖산철 19.75 gIron lactate 19.75 g
산화아연 3.5 g3.5 g of zinc oxide
니코틴산아미드 3.5 gNicotinamide 3.5 g
비타민 A 0.2 g0.2 g of vitamin A
비타민 B1 0.25 g0.25 g of vitamin B 1
비타민 B2 0.3 g0.3 g of vitamin B 2
정제수 정량Purified Water Quantification
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1 시간 동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2ℓ 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다.After mixing the above components according to a conventional healthy beverage production method, and then stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container sealed sterilization and then refrigerated and stored in the present invention For the preparation of healthy beverage compositions.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만 수요계층이나, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is mixed with a component suitable for a favorite beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
하기에 본 발명의 추출물을 함유하는 화장료 조성물의 제조예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, an example of preparation of a cosmetic composition containing an extract of the present invention will be described, but the present invention is not intended to be limited thereto, but is intended to be described in detail.
제조예 1: 영양화장수(밀크로션)Preparation Example 1: Nutrients (Milk Lotion)
데칸알 2.0 중량%Deccanal 2.0 wt%
스쿠알란 5.0 중량%Squalane 5.0 wt%
밀납 4.0 중량%Beeswax 4.0 wt%
폴리솔베이트60 1.5 중량%Polysorbate60 1.5 wt%
솔비탄세스퀴올레이트 1.5 중량%Sorbanthesquioleate 1.5 wt%
유동파라핀 0.5 중량%0.5% by weight of liquid paraffin
카프릴릭/카프릭트리글리세라이드 5.0 중량%Caprylic / Capric Triglycerides 5.0 wt%
글리세린 3.0 중량%Glycerin 3.0 wt%
부틸렌글리콜 3.0 중량%Butylene Glycol 3.0 wt%
프로필렌글리콜 3.0 중량%Propylene Glycol 3.0 wt%
카르복시비닐폴리머 0.1 중량%Carboxy vinyl polymer 0.1 wt%
트리에탄올아민 0.2 중량%0.2% by weight of triethanolamine
방부제, 색소, 향료 적량Preservatives, colorings, flavors
정제수 to 100 중량%Purified water to 100% by weight
상기의 배합비는 비교적 영양화장수에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상적인 화장품 분야에서의 제조방법에 따라 제조할 수 있다. Although the above-mentioned compounding ratio is mixed with a component suitable for nutritional longevity in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
제조예 2: 유연화장수(스킨로션)Preparation Example 2: Softener (Skin Lotion)
데칸알 2.0 중량 %Deccanal 2.0 wt%
글리세린 3.0 중량 %Glycerin 3.0 wt%
부틸렌글리콜 2.0 중량 %Butylene glycol 2.0% by weight
프로필렌글리콜 2.0 중량 %Propylene Glycol 2.0 wt%
카르복시비닐폴리머 0.1 중량 %Carboxy vinyl polymer 0.1 wt%
PEG 12 노닐페닐에테르 0.2 중량 % PEG 12 nonylphenylether 0.2% by weight
폴리솔베이트80 0.4 중량 %Polysorbate 80 0.4% by weight
에탄올 10.0 중량 %Ethanol 10.0 wt%
트리에탄올아민 0.1 중량 %Triethanolamine 0.1% by weight
방부제, 색소, 향료 적량Preservatives, colorings, flavors
정제수 to 100 중량 %Purified water to 100% by weight
상기의 배합비는 비교적 유연화장수에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상적인 화장품 분야에서의 제조방법에 따라 제조할 수 있다. Although the above-mentioned compounding ratio is mixed and formulated in a preferred embodiment with a component suitable for a relatively softening longevity, the compounding ratio may be arbitrarily modified, and can be prepared according to the manufacturing method in the general cosmetic field.
제조예 3: 영양크림Preparation Example 3 Nutrition Cream
데칸알 2.0 중량 % Deccanal 2.0 wt%
폴리솔베이트60 1.5 중량 %Polysorbate 60 1.5% by weight
솔비탄세스퀴올레이트 0.5 중량 %Sorbitan sesquioleate 0.5% by weight
PEG60 경화피마자유 2.0 중량 %PEG60 Cured Castor Oil 2.0% by weight
유동파라핀 10 중량 %10% by weight of liquid paraffin
스쿠알란 5.0 중량 %Squalane 5.0 wt%
카프릴릭/카프릭트리글리세라이드 5.0 중량 %Caprylic / Capric Triglycerides 5.0 wt%
글리세린 5.0 중량 %Glycerin 5.0 wt%
부틸렌글리콜 3.0 중량 %Butylene glycol 3.0% by weight
프로필렌글리콜 3.0 중량 %Propylene Glycol 3.0 Weight%
트리에탄올아민 0.2 중량 %Triethanolamine 0.2% by weight
방부제 적량Preservative
색소 적량Pigment amount
향료 적량Spices
정제수 to 100 중량 %Purified water to 100% by weight
상기의 배합비는 비교적 영양크림에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상적인 화장품 분야에서의 제조방법에 따라 제조할 수 있다. Although the above-mentioned compounding ratio is mixed with a component suitable for nourishing cream in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
제조예 4: 마사지크림Preparation Example 4 Massage Cream
데칸알 1.0 중량 %Deccanal 1.0 wt%
밀납 10.0 중량 %Beeswax 10.0 weight%
폴리솔베이트60 1.5 중량 %Polysorbate 60 1.5% by weight
PEG 60 경화피마자유 2.0 중량 %PEG 60 Cured Castor Oil 2.0% by weight
솔비탄세스퀴올레이트 0.8 중량 %Sorbanthesquioleate 0.8 wt%
유동파라핀 40.0 중량 %40.0% by weight of liquid paraffin
스쿠알란 5.0 중량 %Squalane 5.0 wt%
카프릴릭/카프릭트리글리세라이드 4.0 중량 %Caprylic / Capric Triglyceride 4.0 wt%
글리세린 5.0 중량 %Glycerin 5.0 wt%
부틸렌글리콜 3.0 중량 %Butylene glycol 3.0% by weight
프로필렌글리콜 3.0 중량 %Propylene Glycol 3.0 Weight%
트리에탄올아민 0.2 중량 %Triethanolamine 0.2% by weight
방부제, 색소, 향료 적량Preservatives, colorings, flavors
정제수 to 100 중량 %Purified water to 100% by weight
상기의 배합비는 비교적 마사지크림에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상적인 화장품 분야에서의 제조방법에 따라 제조할 수 있다. Although the above-mentioned compounding ratio is mixed with a component suitable for a massage cream in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a manufacturing method in the general cosmetic field.
제조예 4: 팩Preparation Example 4 Pack
데칸알 1.0 중량 %Deccanal 1.0 wt%
폴리비닐알콜 13.0 중량 %Polyvinyl alcohol 13.0 wt%
소듐카르복시메틸셀룰로오스 0.2 중량 %Sodium Carboxymethylcellulose 0.2% by weight
글리세린 5.0 중량 %Glycerin 5.0 wt%
알란토인 0.1 중량 %Allantoin 0.1 wt%
에탄올 6.0 중량 %Ethanol 6.0 wt%
PEG 12 노닐페닐에테르 0.3 중량 % PEG 12 nonylphenyl ether 0.3% by weight
폴리솔베이트60 0.3 중량 %Polysorbate60 0.3 wt%
방부제, 색소, 향료 적량Preservatives, colorings, flavors
정제수 to 100 중량 %Purified water to 100% by weight
상기의 배합비는 비교적 팩에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상적인 화장품 분야에서의 제조방법에 따라 제조할 수 있다. Although the above-mentioned compounding ratio is mixed with a component suitable for a pack in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a manufacturing method in the general cosmetic field.
제조예 6: 젤Preparation Example 6 Gel
데칸알 0.5 중량 %Deccanal 0.5 wt%
에틸렌디아민초산나트륨 0.05 중량 %0.05% by weight of ethylenediamine sodium acetate
글리세린 5.0 중량 %Glycerin 5.0 wt%
카르복시비닐폴리머 0.3 중량 %Carboxy vinyl polymer 0.3 wt%
에탄올 5.0 중량 %Ethanol 5.0 wt%
PEG 60 경화피마자유 0.5 중량 %PEG 60 Cured Castor Oil 0.5% by weight
트리에탄올아민 0.3 중량 %0.3% by weight of triethanolamine
방부제, 색소, 향료 적량Preservatives, colorings, flavors
정제수 to 100 중량 %Purified water to 100% by weight
상기의 배합비는 비교적 젤에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상적인 화장품 분야에서의 제조방법에 따라 제조할 수 있다. Although the above-mentioned compounding ratio is mixed with a component suitable for a gel in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
상기 배합비는 비교적 화장료 조성물에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그외의 색채 화장품을 포함하는 다양한 용도의 화장품에 적용될 수 있는 것이고, 그 효능에 따라 인체에 얇게 도포하여 바를 수 있는 약제 즉, 연고로 제조에 이용될 수 있으며 수요계층이나, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.The blending ratio is a relatively suitable composition for the cosmetic composition in a preferred embodiment, but can be applied to cosmetics of various uses, including other color cosmetics, according to the efficacy that can be applied to a thin coating on the human body, that is, It can be used for manufacturing as an ointment, and the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 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.The foregoing description of the present invention is intended for illustration, and it will be understood by those skilled in the art that the present invention may be easily modified in other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are exemplary in all respects and not restrictive.
Claims (12)
- 하기 화학식 1로 표시되는 데칸알(Decanal) 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 질환 예방 또는 치료용 약학적 조성물.A pharmaceutical composition for preventing or treating muscle diseases comprising a decanal compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.[화학식 1][Formula 1]
- 제1항에 있어서, The method of claim 1,상기 조성물은 p-4E-BP1 또는 p-p70S6K1 단백질의 발현을 증가시키는 것을 특징으로 하는 The composition is characterized in that to increase the expression of p-4E-BP1 or p-p70S6K1 protein근육 질환 예방 또는 치료용 약학적 조성물. Pharmaceutical composition for preventing or treating muscle diseases.
- 제1항에 있어서, The method of claim 1,상기 조성물은 MuRF1(Muscle Ring-Finger Protein) 또는 MaFbx(Muscle atrophy F-box)의 발현을 감소시키는 것을 특징으로 하는 The composition is characterized by reducing the expression of the mucle ring-finger protein (MuRF1) or muscle atrophy F-box (MaFbx)근육 질환 예방 또는 치료용 약학적 조성물. Pharmaceutical composition for preventing or treating muscle diseases.
- 제1항에 있어서, The method of claim 1,상기 화합물은 0.1 내지 1000μM의 농도로 조성물에 포함되는 것을 특징으로 하는 The compound is characterized in that it is included in the composition at a concentration of 0.1 to 1000μM근육 질환 예방 또는 치료용 약학적 조성물.Pharmaceutical composition for preventing or treating muscle diseases.
- 제1항에 있어서, The method of claim 1,상기 근육 질환은 근 기능 저하, 근육 감소, 근육 소모 또는 근육 퇴화로 인한 근육 질환인 것을 특징으로 하는 The muscle disease is characterized in that the muscle disease due to muscle function decline, muscle reduction, muscle wasting or muscle degeneration근육 질환 예방 또는 치료용 약학적 조성물.Pharmaceutical composition for preventing or treating muscle diseases.
- 제1항 내지 제5항 중 어느 한 항에 있어서, The method according to any one of claims 1 to 5,상기 근육 질환은 긴장감퇴증(atony), 근위축증(muscular atrophy), 근이영양증(muscular dystrophy), 근무력증, 악액질(cachexia), 경직성 척추 증후군(rigid spinesyndrome), 근위축성 측삭경화증(루게릭병, amyotrophic lateral sclerosis), 경직성 척추 증후군(rigid spinsesyndrome), 샤르코-마리-투스병(Charcot-Marie-Tooth disease) 및 근육 감소증(sarcopenia)으로 이루어진 군으로부터 선택되는 어느 하나 이상인 것을 특징으로 하는 The muscle diseases include atony, muscular atrophy, muscular dystrophy, myasthenia, cachexia, rigid spinesyndrome, amyotrophic lateral sclerosis , At least one selected from the group consisting of rigid spinse syndrome, Charcot-Marie-Tooth disease, and sarcopenia.근육 질환 예방 또는 치료용 약학적 조성물.Pharmaceutical composition for preventing or treating muscle diseases.
- 하기 화학식 1로 표시되는 데칸알(Decanal) 화합물 또는 이의 식품학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 질환 예방 또는 개선용 건강기능성 식품 조성물.Decanal compound represented by the formula (1) or a health functional food composition for preventing or improving muscle diseases comprising a food acceptable salt thereof as an active ingredient.[화학식 1][Formula 1]
- 하기 화학식 1로 표시되는 데칸알(Decanal) 화합물 또는 이의 식품학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 분화 촉진, 근육 재생 또는 근육 강화용 약학적 조성물.A pharmaceutical composition for promoting muscle differentiation, muscle regeneration, or muscle strengthening, comprising a decanal compound represented by Formula 1 or a food acceptable salt thereof as an active ingredient.[화학식 1][Formula 1]
- 하기 화학식 1로 표시되는 데칸알(Decanal) 화합물 또는 이의 식품학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 분화 촉진, 근육 재생 또는 근육 강화용 건강기능성 식품 조성물.A health functional food composition for promoting muscle differentiation, muscle regeneration, or muscle enhancement, comprising a decanal compound represented by Formula 1 or a food acceptable salt thereof as an active ingredient.[화학식 1][Formula 1]
- 제11항에 있어서, The method of claim 11,상기 가축은 소, 돼지, 닭, 오리, 염소, 양 및 말로 이루어진 군 중에서 선택된 1종의 가축인 것을 특징으로 하는 The livestock is a cattle, pigs, chickens, ducks, goats, sheep and horses, characterized in that one of the cattle selected from the group consisting of근육 질환 예방 또는 치료용 가축 사료용 조성물Livestock feed compositions for the prevention or treatment of muscle diseases
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US20140302023A1 (en) * | 2011-11-07 | 2014-10-09 | UNIVERSITé LAVAL | Use of rank/rankl antagonists for treating neuromuscular disorders, genetic myopathies and/or non genetic myopathies and/or for regulating skeletal and cardiac muscle disuse, diseases and aging |
KR20150024586A (en) * | 2013-08-27 | 2015-03-09 | (주)네오팜 | A composition and external application for acceleration of muscle differentiation and improving of muscle mass |
KR20150142536A (en) * | 2014-06-12 | 2015-12-22 | 한국생명공학연구원 | Pharmaceutical composition for preventing or treating muscle weakness diseases comprising Butylpyridinium or derivatives thereof |
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WO2013168021A1 (en) * | 2012-05-07 | 2013-11-14 | Mahesh Kandula | Compositions and methods for treatment of neuromuscular disorders and neurodegenerative disorders |
KR20140042759A (en) * | 2012-09-28 | 2014-04-07 | 한국생명공학연구원 | Pharmaceutical composition for preventing or treating muscle weakness diseases comprising acecainide or derivatives thereof |
KR20150024586A (en) * | 2013-08-27 | 2015-03-09 | (주)네오팜 | A composition and external application for acceleration of muscle differentiation and improving of muscle mass |
KR20150142536A (en) * | 2014-06-12 | 2015-12-22 | 한국생명공학연구원 | Pharmaceutical composition for preventing or treating muscle weakness diseases comprising Butylpyridinium or derivatives thereof |
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