KR20140086186A - Composition comprising s-allyl-l-cysteine for treating obesity-induced inflammation - Google Patents
Composition comprising s-allyl-l-cysteine for treating obesity-induced inflammation Download PDFInfo
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- KR20140086186A KR20140086186A KR1020120156374A KR20120156374A KR20140086186A KR 20140086186 A KR20140086186 A KR 20140086186A KR 1020120156374 A KR1020120156374 A KR 1020120156374A KR 20120156374 A KR20120156374 A KR 20120156374A KR 20140086186 A KR20140086186 A KR 20140086186A
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- South Korea
- Prior art keywords
- cysteine
- composition
- adiponectin
- allyl
- arylcysteine
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- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
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Abstract
Description
본 발명은 S-아릴 시스테인을 유효성분으로 함유하는 비만으로 유도된 염증 치료용 조성물에 관한 것이다.The present invention relates to a composition for treating inflammation induced by obesity containing S-arylcysteine as an active ingredient.
비만은 인슐린 저항성, 제 2형 당뇨, 동맥경화, 고지혈증, 비알콜성 지방간 질환의 발생에 직접적인 원인으로 작용하며, 허혈성 심질환, 치매, 암, 류마티스 관절염, 역류성 식도염, 고혈압 등 수많은 대사성 질환과 직간접적의 원인이 될 수 있다. 최근 비만이 경증 염증 상태를 유발하여 관련 대사성 질환을 유발한다는 증거가 크게 늘어나고 있다. 특히 지방 조직은 잉여의 에너지를 저장하는 역할 뿐만 아니라 여러 종류의 생리활성 물질 생성하는 내분비 기관으로 규명되었다. 비만도가 높거나 지방세포의 기능이상이 일어나면 지방조직에서 분비하는 생리활성 물질이 비정상적으로 발현하여 면역반응이 변화하게 되며 이는 많은 대사성질환의 발생과 진행에 영향을 준다.
Obesity is a direct cause of the development of insulin resistance,
지방 조직에서 분비되는 생리활성 성분은 주로 싸이토카인과 키모카인으로 크게 호염증성 (pro-inflammatory)과 항염증성 (anti-inflammatory) 성분, 그리고 대사 기능 조절 성분으로 나눌 수 있다. 대표적인 호염증성 성분으로는 종양괴사인자-알파 (tumor necrosis factor-α, TNF-α), 인터루킨-6 (interleukin-6, IL-6), 단핵세포 주화성 단백질 (Monocyte chemoattractant protein 1, MCP-1) 등이 있으며 항염증성 성분에는 아티포넥틴 (adiponectin)이 있으며 마지막으로 대사기능 조절 성분에는 렙틴 (leptin)과 아디포넥틴 등이 있다.
The physiologically active components secreted from adipose tissue are mainly cytokine and chymocaine, which can be classified into pro-inflammatory, anti-inflammatory and metabolic regulation components. Representative inflammatory components include tumor necrosis factor-alpha, TNF-a, interleukin-6, IL-6,
최근의 연구 결과, 지방조직에서 유래한 MCP-1은 지방조직내로 대식세포의 이주를 유도하였고 이에 따라 지방조직내 염증 반응을 증폭시켰다. 이에 반해, 아디포넥틴은 골격 근육내 인슐린 수용체 기질-1의 발현을 증가하여 인슐린 민감성을 향상시키고, 혈관 내피 세포내 부착성 분자의 발현을 억제하고, 혈관 내벽 단핵세포/대식세포-유래 거품세포의 축적을 방해하여 동맥경화 병변과정을 저해한다. Recent studies have shown that MCP-1 derived from adipose tissue induces migration of macrophages into adipose tissue, thereby amplifying the inflammatory response in adipose tissue. In contrast, adiponectin enhances insulin sensitivity by increasing the expression of insulin receptor substrate-1 in skeletal muscle, inhibits the expression of adherent molecules in vascular endothelial cells, accumulates vascular endothelial mononuclear cells / macrophage-derived foam cells Interferes with the atherosclerotic lesion process.
이 같은 발견은 지방 조직에서 분비되는 생리활성 성분의 분비 조절이상이 비만성 질환의 진행에 중요한 역할을 하고 따라서 이 같은 생리활성 성분의 조절은 비만-유도 염증뿐만 아니라 비만성 질환의 진행을 제어하는데 유용한 타켓임을 제시한다.
This finding suggests that the regulation of the secretion of physiologically active components secreted by adipose tissue plays an important role in the progression of obesity, and thus the regulation of such physiologically active components controls not only obesity-induced inflammation but also the progression of obesity Suggest a useful target.
이에 본 발명자들은 지방 조직에서 분비되는 생리활성 성분의 분비를 조절할 수 있는 물질을 발견하여 본 발명에 이르렀다.Accordingly, the present inventors have discovered a substance capable of regulating secretion of a physiologically active ingredient secreted from adipose tissue, and have reached the present invention.
본 발명은 S-아릴 시스테인을 유효성분으로 함유하는 비만으로 유도된 염증을 개선하는 조성물을 제공하는데 그 목적이 있다.It is an object of the present invention to provide a composition for improving obesity-induced inflammation containing S-arylcysteine as an active ingredient.
상기의 목적을 달성하기 위하여 본 발명의 일 구체예에서 S-아릴 시스테인(S-Allyl-L-Cysteine)을 유효성분으로 함유하는 염증 예방 및 치료용 약학조성물을 제공한다.In order to achieve the above object, there is provided a pharmaceutical composition for preventing and treating inflammation comprising S-Allyl-L-Cysteine as an active ingredient in one embodiment of the present invention.
다른 구체예에서 S-아릴 시스테인(S-Allyl-L-Cysteine)을 유효성분으로 함유하는 염증 예방 및 개선용 건강기능식품을 제공한다.In another embodiment, there is provided a health functional food for preventing and improving inflammation containing S-Allyl-L-Cysteine as an active ingredient.
또 다른 구체예에서 S-아릴 시스테인(S-Allyl-L-Cysteine)을 유효성분으로 함유하는 대사성 질환 예방 및 치료용 약학조성물을 제공한다.In another embodiment, there is provided a pharmaceutical composition for preventing and treating metabolic diseases containing S-Allyl-L-Cysteine as an active ingredient.
또 다른 구체예에서 S-아릴 시스테인(S-Allyl-L-Cysteine)을 유효성분으로 함유하는 대사성 질환 예방 및 개선용 건강기능식품을 제공한다.In another embodiment, there is provided a health functional food for preventing and improving metabolic diseases containing S-Allyl-L-Cysteine as an active ingredient.
본 발명에 있어서 상기 S-아릴 시스테인(S-Allyl-L-Cysteine)은 IL-6 및 MCP-1 발현을 억제하는 것을 특징으로 하고, 상기 테트란드린은 아디포넥틴의 분비를 증가시키는 것을 특징으로 하며, 상기 조성물은 캡슐, 정제, 과립, 분말 또는 음료 형태임을 특징으로 한다.In the present invention, the S-Allyl-L-Cysteine inhibits the expression of IL-6 and MCP-1, and the Tetrandrine is characterized in that the secretion of adiponectin is increased , Wherein the composition is in the form of a capsule, tablet, granule, powder or beverage.
본 발명에서 S-아릴 시스테인은 수용성 유황화합물로 항산화 작용, 간 장애 예방작용, 암의 예방작용, 암세포 증식 억제작용 등의 약리작용을 갖는 것이 보고 되어 있으며 하기 화학식 1과 같이 나타낸다.In the present invention, S-arylcysteine is a water-soluble sulfur compound and has been reported to have a pharmacological action such as an antioxidative action, a liver disorder prevention action, a cancer prevention action, a cancer cell proliferation inhibitory action, and the like.
[화학식 1][Chemical Formula 1]
본 발명에 있어서 아디포넥틴은 크기가 약 30 kDa인 호르몬 유사(hormone like) 성분으로 항염증, 항동맥경화, 인슐린저항성 개선 등의 역할을 한다. 비만인 사람의 혈중 아디포넥틴 농도가 체중이 정상인 사람에 비해 크게 낮은 것으로 보고된 이후, 많은 연구를 통해 혈중 아디포넥틴 농도는 체질량지수(body mass index, BMI)에 반비례 한다고 밝혀내었으며 당뇨와 심혈관 질환이 있는 비만환자의 혈중 아디포넥틴 농도가 감소하는 것으로 나타났다. 또한 최근 연구결과에 따르면 혈중 아디포넥틴 농도는 지방조직 중 대사성질환과 밀접한 관련이 있는 내장지방의 크기와 반비례하는 것으로 나타났다.In the present invention, adiponectin is a hormone-like component having a size of about 30 kDa and plays an anti-inflammatory, anti-arteriosclerosis and insulin resistance improvement. Since adiponectin levels in obese people have been reported to be significantly lower than those in normal people, many studies have shown that blood adiponectin levels are inversely proportional to body mass index (BMI), and diabetes and obesity with cardiovascular disease The patient's serum adiponectin levels were found to decrease. Recent studies also show that plasma adiponectin levels are inversely proportional to the size of visceral fat, which is closely related to metabolic disease in adipose tissue.
지방조직이 아디포넥틴의 대부분을 생산하면서도 아디포넥틴 농도가 비만도에 반비례하는 이유는 염증 인자가 아디포넥틴의 생성을 저해하기 때문이다. 대표적인 염증 인자인 종양괴사인자-알파와 대표적인 염증원인 지질다당체 (lipopolysaccharide, LPS)는 아디포넥틴 발현을 억제한다. 또한 아디포넥틴은 단핵구세포, 대식세포, 수지상세포와 같은 면역세포가 항염증 성분인 IL-10, IL-1 receptor antagonist (IL-1 RA)의 생성을 증가시킨다. 그 외에도 비만이거나 당뇨인 환자에 있어 대표적인 염증 인자인 C-reactive protein (CRP)의 혈중 농도는 아디포넥틴에 반비례하며, 정상 체중이거나 당뇨병에 걸리지 않은 경우라 해도 아디포넥틴 농도가 감소하는 경우 CRP 농도는 증가한다. 아디포넥틴이 부족한 생쥐의 경우, TNF-a의 mRNA 농도가 증가하며 이는 혈중 TNFa의 증가로 연결된다. 대표적인 비만 동물모델인 ob/ob 생쥐에 아디포넥틴의 과발현을 유도하는 경우, 비만은 발생하지만 당대사가 개선되며 지방조직에 침투한 대식세포의 농도가 감소하며 지방조직내 TNF 발현이 감소하는 등의 염증 개선 효과가 나타난다. 또한 ob/ob 생쥐에 재조합 아디포넥틴을 주입하는 경우에도 지방간의 개선과 TNF 생산이 감소한다. 따라서 아디포넥틴은 염증과 밀접한 관련이 있으며 아디포넥틴의 발현이 증가하는 경우 비만의 개선 없이 비만에 의해 매개되는 염증 반응 (비만염증) 또는 비만염증으로 인해 발생하는 동맥경화와 같은 대사성질환이 개선되는 효과가 있다.
The reason that adiponectin is inversely proportional to the obesity index while fat tissue produces most of adiponectin is because the inflammatory factor inhibits the production of adiponectin. Tumor necrosis factor-alpha, a typical inflammatory factor, and lipopolysaccharide (LPS), a typical inflammatory agent, inhibit adiponectin expression. In addition, adiponectin increases the production of IL-10, IL-1 receptor antagonist (IL-1 RA), an anti-inflammatory component, in immune cells such as monocytes, macrophages and dendritic cells. In addition, the plasma concentration of C-reactive protein (CRP), which is a typical inflammatory factor in obese or diabetic patients, is inversely proportional to adiponectin and increases with increasing adiponectin concentration even when normal weight or diabetes is not experienced. In mice lacking adiponectin, the mRNA level of TNF-a is increased, leading to an increase in TNFa in the blood. Induction of overexpression of adiponectin in a representative obesity animal model, ob / ob mice, leads to obesity but improves the metabolism, decreases the concentration of macrophages infiltrating adipose tissue, and decreases the expression of TNF in adipose tissue Effect appears. Injection of recombinant adiponectin into ob / ob mice also reduces fatty liver improvement and TNF production. Therefore, adiponectin is closely related to inflammation, and when the expression of adiponectin is increased, metabolic diseases such as arteriosclerosis caused by obesity-induced inflammatory reaction (obesity inflammation) or obesity inflammation are improved without improvement of obesity .
본 발명의 조성물은, 조성물 총 중량에 대하여 상기 S-아릴 시스테인을 0.1 내지 50 중량%로 포함한다. 본 발명의 S-아릴 시스테인을 포함하는 조성물은 통상의 방법에 따른 적절한 담체, 부형제 또는 희석제를 추가로 포함할 수 있다. 본 발명의 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 본 발명에 따른 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 또는 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 상세하게는, 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 S-아릴 시스테인에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트 (calcium carbonate), 수크로스 (sucrose), 락토오스 (lactose), 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용될 수 있다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는 데, 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제 및 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜 (propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔 (witepsol), 마크로골, 트윈 (tween) 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있다.The composition of the present invention comprises the above S-aryl cysteine relative to the total weight of the composition 0.1 to 50% by weight. The compositions comprising S-arylcysteine of the present invention may further comprise suitable carriers, excipients or diluents according to conventional methods. Examples of carriers, excipients and diluents that can be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. The composition according to the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols or the like, oral preparations, suppositories or sterilized injection solutions according to a conventional method have. More specifically, when formulating the composition, it can be prepared using a diluent or an excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, and the like. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, syrups and the like, and various excipients such as wetting agents, sweeteners, fragrances, preservatives, etc. in addition to commonly used diluents such as water and liquid paraffin . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.
본 발명은 환자의 나이, 성별, 체중에 따라 달라질 수 있으나, 일반적으로 0.01 내지 500 mg/㎏의 양, 바람직하게는 0.1 내지 100 mg/㎏의 양을 일일 1회 내지 수회로 나누어 투여할 수 있다. 또한 그 투여량은 투여경로, 질병의 정도, 성별, 체중, 나이 등에 따라서 증감될 수 있다. 따라서, 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. The present invention may be varied depending on the age, sex and body weight of the patient, but it is generally administered in an amount of 0.01 to 500 mg / kg, preferably 0.1 to 100 mg / kg, once to several times per day . The dosage may also be increased or decreased depending on the route of administration, degree of disease, sex, weight, age, and the like. Thus, the dosage amounts are not intended to limit the scope of the invention in any manner.
본 발명의 조성물은 랫트, 마우스, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식이 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌실내 (intracerebroventricular) 주사에 의해 투여될 수 있다. 본 발명의 S-아릴 시스테인은 독성 및 부작용은 거의 없으므로 예방 목적으로 장기간 복용시에도 안심하고 사용할 수 있다. The composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections. Since the S-aryl cysteine of the present invention has little toxicity and side effects, it can be safely used for prolonged use even for prophylactic purposes.
본 발명은 상기 S-아릴 시스테인 및 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 건강 기능 식품을 제공하는데, 각종 식품류, 예를 들어, 음료, 껌, 차, 비타민 복합제, 건강보조 식품류 등이 있으며, 환제, 분말, 과립, 침제, 정제, 캡슐 또는 음료인 형태로 사용할 수 있다. 이때, 식품 또는 음료 중의 상기 S-아릴 시스테인의 양은, 일반적으로 본 발명의 건강식품 조성물의 경우 전체 식품 중량의 0.01 내지 15 중량%로 가할 수 있으며, 건강 음료 조성물의 경우 100 ㎖를 기준으로 0.02 내지 10 g, 바람직하게는 0.3 내지 1 g의 비율로 가할 수 있다.The present invention provides a health functional food comprising the above-mentioned S-aryl cysteine and a pharmaceutically acceptable food supplementary additive, and it can be various foods such as beverage, gum, tea, vitamin complex, Pills, powders, granules, precipitates, tablets, capsules or beverages. In this case, the amount of the S-arylcysteine in the food or beverage may be generally 0.01 to 15% by weight of the total food weight of the health food composition of the present invention, and 0.02 to 100% 10 g, preferably 0.3 to 1 g.
본 명세서에서 정의되는 식품보조첨가제는 당업계에 통상적인 식품첨가제, 예를 들어 향미제, 풍미제, 착색제, 충진제, 안정화제 등을 포함한다. 본 발명에 따른 건강 음료 조성물은 지시된 비율로 필수 성분으로서, 상기 S-아릴 시스테인 외에 첨가되는 성분에 특별한 제한은 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상기 천연 탄수화물의 예로는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린; 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제 (타우마틴, 스테비아 추출물 (예를 들어 레바우디오시드 A, 글리시르히진 등)) 및 합성 향미제 (사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ㎖당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12g이다.Food supplementary additives as defined herein include food additives customary in the art, such as flavoring agents, flavoring agents, coloring agents, fillers, stabilizers, and the like. The health beverage composition according to the present invention is not particularly limited as to the ingredient to be added in addition to the S-aryl cysteine as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates as an additional ingredient have. Examples of the natural carbohydrate include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; Polysaccharides such as dextrin, cyclodextrins; And sugar alcohols such as xylitol, sorbitol, and erythritol. As natural flavors other than those described above, natural flavors (such as tau martin, stevia extract (e.g., rebaudioside A, glycyrrhizin)) and synthetic flavors (saccharin, aspartame, etc.) have. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 광물 (전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제 (치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 조성물들은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and intermediates (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
이상에서 설명한 바와 같이, 본 발명에 의한 조성물은 아디포넥틴의 발현을 유도하고 비만 매개 염증 반응에 관여하는 IL-6 및 MCP-1의 발현을 감소시켜 비만으로 유도된 염증을 예방 및 치료할 수 있다.As described above, the composition of the present invention can prevent and treat inflammation induced by obesity by inducing the expression of adiponectin and reducing the expression of IL-6 and MCP-1, which are involved in an obesity-mediated inflammatory reaction.
도 1은 S-아릴 시스테인을 농도별로 처리한 처리구의 아디포넥틴 농도를 나타낸 그래프이다.
도 2는 S-아릴 시스테인을 농도별로 처리한 처리구의 IL-6 농도를 나타낸 그래프이다.
도 3은 S-아릴 시스테인을 농도별로 처리한 처리구의 MCP-1 농도를 나타낸 그래프이다.
도 4는 S-아릴 시스테인의 독성실험결과 그래프이다.1 is a graph showing the concentration of adiponectin in the treatment group treated with S-arylcysteine at a concentration.
FIG. 2 is a graph showing the IL-6 concentration in the treatment group treated with S-arylcysteine at different concentrations.
FIG. 3 is a graph showing the MCP-1 concentration of the treatment group treated with S-arylcysteine at different concentrations.
Fig. 4 is a graph showing the toxicity test result of S-arylcysteine.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다.
Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .
실시예Example
실시예Example 1. 지방세포의 배양 1. Culture of adipocytes
지방 전구세포인 3T3-L1 세포(ATCC(American Tissue Culture Collection, USA)로부터 구입)에 호르몬 혼합물 (인슐린 10 μg/ml, 3-이소부틸-1-메틸잔틴 0.5 mM, 및 덱사메타손 1 μg/ml)을 배양배지에 혼합하여 처리한 뒤 이틀을 배양하고, 인슐린 10 μg/ml을 배양배지에 혼합하여 이틀을 배양한 뒤 마지막으로 배양배지를 이틀을 처리하여 지방세포분화를 유도하였다.
(
실시예Example 2. S-아릴 시스테인(S- 2. S-aryl cysteine (S- AllylAllyl -L--L- CysteineCysteine )에 따른 염증 인자 농도 측정) Of inflammatory factor concentration
상기 실시예 1의 지방세포를 혈청이 없는 배지상에서 밤새 (overnight) 기아배양 (starvation)을 한 뒤 종양괴사인자 알파 (TNF-alpha)를 20ng/ml의 농도로 처리하여 염증을 유도하였으며, 동시에 S-아릴 시스테인(S-Allyl-L-Cysteine)을 농도별로 처리한 뒤 24 시간을 배양하였다.The adipocytes of Example 1 were starvated overnight in serum-free medium and then treated with TNF-alpha at a concentration of 20 ng / ml to induce inflammation, while S - S-Allyl-L-Cysteine was cultured for 24 hours.
24시간 배양 후 배양액을 분리하여 ELISA의 방법으로 세포가 분비한 아디포넥틴, IL-6 및 MCP-1 함량을 측정였다. 그 결과, S-아릴 시스테인을 처리한 처리구에서 아디포넥틴의 발현이 유도되는 것을 확인할 수 있었고(도 1 참조), 지방 조직에 특이적이지 않지만 염증 반응에 관여하는 IL-6 및 MCP-1의 농도가 감소하는 것을 확인할 수 있었다(도 2 및 도 3 참조).
After culturing for 24 hours, the cultures were separated and the contents of adiponectin, IL-6 and MCP-1 secreted by ELISA were measured. As a result, it was confirmed that the expression of adiponectin was induced in S-arylcysteine-treated treatment (see FIG. 1), and the concentrations of IL-6 and MCP-1, which are not specific to adipose tissue, (See Figs. 2 and 3).
실시예Example 3. S-아릴 시스테인(S- 3. S-aryl cysteine (S- AllylAllyl -L--L- CysteineCysteine )의 혈관내피세포에 대한 독성 검사) To vascular endothelial cell toxicity test
S-아릴 시스테인에 의한 염증 억제력이 독성에 의한 것이 아님과 임상 및 식품에 이용하기 위해 독성검사를 실시하였다. 혈관내피세포에 0, 6.25, 12.5, 25 및 50μM S-아릴 시스테인을 혼합하여 16시간 배양 후, WST-1 키트 (Roche Applied Science, Indianapolis, IN, USA)를 이용하여 세포의 생존율을 측정하였다.The anti-inflammatory effects of S-arylcysteine were not due to toxicity and toxicity tests were performed for clinical use and food use. Vascular endothelial cells were mixed with 0, 6.25, 12.5, 25, and 50 μM S-arylcysteine for 16 hours, and cell viability was measured using a WST-1 kit (Roche Applied Science, Indianapolis, IN, USA).
실험결과, 도 4에서와 같이, 0, 6.25, 12.5, 25 및 50μM S-아릴 시스테인에서 혈관내피세포의 생존율이 변함이 없음을 확인할 수 있으며, 이에 의하면 도 1 및 3에서 사용된 1-50 μM S-아릴 시스테인에서의 실험결과는 독성에 의한 영향이 아님을 입증한다. 이로부터 본 발명에서의 활성성분인 에보디아민은 혈관내피세포에 독성을 주지 않고 염증을 억제시키는 것을 실시예 1 및 2에서 확인할 수 있었다.
As shown in FIG. 4, the survival rate of vascular endothelial cells was not changed in 0, 6.25, 12.5, 25, and 50 μM S-aryl cysteine. Experimental results with S-aryl cysteine demonstrate that this is not a toxic effect. From these results, it was confirmed in Examples 1 and 2 that the active ingredient ebola diamine in the present invention inhibits inflammation without giving toxicity to vascular endothelial cells.
하기에 본 발명의 조성물을 위한 제제예를 예시한다. 단, 하기 제제예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 제제예에 의해 한정되는 것은 아니다.
Examples of formulations for the composition of the present invention are illustrated below. However, the following formulation examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following formulation examples.
제제예Formulation example 1: One: 산제의Sanje 제조 Produce
S-아릴 시스테인 ------------------------------- 300 mgS-aryl cysteine ------------------------------- 300 mg
유당 ------------------------------------------100 mgLactose ------------------------------------------ 100 mg
탈크 -------------------------------------------10 mgTalc ------------------------------------------- 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.
The above components are mixed and filled in airtight bags to prepare powders.
제제예Formulation example 2: 정제의 제조 2: Preparation of tablets
S-아릴 시스테인 --------------------------------50 mgS-aryl cysteine -------------------------------- 50 mg
옥수수전분-------------------------------------100 mgCorn starch ------------------------------------- 100 mg
유당 ------------------------------------------100 mgLactose ------------------------------------------ 100 mg
스테아린산 마그네슘------------------------------2 mgMagnesium stearate ------------------------------ 2 mg
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.
After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.
제제예Formulation example 3: 캡슐제의 제조 3: Preparation of capsules
S-아릴 시스테인----------------------------------50 mgS-
옥수수전분 -------------------------------------100 mgCorn starch ------------------------------------- 100 mg
유당 -------------------------------------------100 mgLactose ------------------------------------------- 100 mg
스테아린산 마그네슘-------------------------------2 mgMagnesium stearate ------------------------------- 2 mg
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.
The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.
제제예Formulation example 4: 주사제의 제조 4: Preparation of injection
S-아릴 시스테인 -------------------------------50 mgS-aryl cysteine ------------------------------- 50 mg
주사용 멸균 증류수------------------------------적량Sterile sterilized distilled water for injection ------------------------------
pH 조절제---------------------------------------적량pH adjusting agent ---------------------------------------
통상의 주사제의 제조방법에 따라 1 앰플당 (2㎖) 상기의 성분 함량으로 제조한다.
(2 ml) per 1 ampoule according to the usual injection preparation method.
제제예Formulation example 5: 5: 액제의Liquid 제조 Produce
S-아릴 시스테인 ------------------------------100 mgS-aryl cysteine ------------------------------ 100 mg
이성화당-----------------------------------------10 gIsing Party ----------------------------------------- 10 g
만니톨--------------------------------------------5 gMannitol -------------------------------------------- 5 g
정제수-------------------------------------------적량Purified water -------------------------------------------
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100 ㎖로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.
Each component was added to purified water in accordance with the usual liquid preparation method and dissolved, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was adjusted to 100 ml with purified water, And sterilized to prepare a liquid preparation.
제제예Formulation example 6: 건강 식품의 제조 6: Manufacture of health food
S-아릴 시스테인 -------------------------------1000 ㎎S-arylcysteine ------------------------------- 1000 mg
비타민 혼합물-------------------------------------적량Vitamin mixture -------------------------------------
비타민 A 아세테이트------------------------------70 ㎍Vitamin A Acetate ------------------------------ 70 g
비타민 E-----------------------------------------1.0 ㎎Vitamin E ----------------------------------------- 1.0 mg
비타민 B1---------------------------------------0.13 ㎎Vitamin B1 --------------------------------------- 0.13 mg
비타민 B2---------------------------------------0.15 ㎎Vitamin B2 --------------------------------------- 0.15 mg
비타민 B6---------------------------------------0.5 ㎎Vitamin B6 --------------------------------------- 0.5 mg
비타민 B12 -------------------------------------0.2 ㎍Vitamin B12 ------------------------------------- 0.2 g
비타민 C-----------------------------------------10 ㎎Vitamin C ----------------------------------------- 10 mg
비오틴-------------------------------------------10 ㎍Biotin ------------------------------------------- 10 [mu] g
니코틴산아미드----------------------------------1.7 ㎎Nicotinic acid amide 1.7 mg
엽산-------------------------------------------- 50 ㎍Folic acid -------------------------------------------- 50 μg
판토텐산 칼슘-----------------------------------0.5 ㎎Calcium pantothenate ----------------------------------- 0.5 mg
무기질 혼합물-------------------------------------적량Inorganic 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 phosphate monohydrate 15 mg
제2인산칼슘 --------------------------------------55 ㎎Secondary calcium phosphate -------------------------------------- 55 mg
구연산칼륨---------------------------------------90 ㎎Potassium citrate --------------------------------------- 90 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 mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.
제제예Formulation example 7: 건강 음료의 제조 7: Manufacture of health drinks
S-아릴 시스테인 -------------------------- 1000 ㎎S-aryl cysteine 1000 mg
구연산---------------------------------------1000 ㎎Citric acid --------------------------------------- 1000 mg
올리고당---------------------------------------100 gOligosaccharides --------------------------------------- 100 g
매실농축액 ------------------------------------- 2 gPlum concentrate ------------------------------------- 2 g
타우린-------------------------------------------1 gTaurine ------------------------------------------- 1 g
정제수를 가하여 전체-------------------------- 900 ㎖Purified water was added to the whole to 900 ml
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간 동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2l용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다. The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The resulting solution was filtered and sterilized in a sterilized 2 liter container, ≪ / RTI >
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 compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.
Claims (18)
상기 S-아릴 시스테인은 IL-6 및 MCP-1 발현을 억제하는 것을 특징으로 하는 약학조성물.The method according to claim 1,
Wherein said S-aryl cysteine inhibits IL-6 and MCP-I expression.
상기 S-아릴 시스테인은 아디포넥틴의 분비를 증가시키는 것을 특징으로 하는 약학조성물.The method according to claim 1,
Wherein said S-arylcysteine increases the secretion of adiponectin.
상기 조성물은 캡슐, 정제, 과립, 분말 또는 음료 형태임을 특징으로 하는 약학조성물. The method according to claim 1,
Wherein said composition is in the form of a capsule, tablet, granule, powder or beverage.
상기 S-아릴 시스테인은 IL-6 및 MCP-1 발현을 억제하는 것을 특징으로 하는 건강기능식품.6. The method of claim 5,
Wherein said S-aryl cysteine inhibits IL-6 and MCP-1 expression.
상기 S-아릴 시스테인은 아디포넥틴의 분비를 증가시키는 것을 특징으로 하는 건강기능식품.6. The method of claim 5,
Wherein said S-arylcysteine increases the secretion of adiponectin.
상기 조성물은 캡슐, 정제, 과립, 분말 또는 음료 형태임을 특징으로 하는 건강기능식품. 6. The method of claim 5,
Wherein said composition is in the form of a capsule, tablet, granule, powder or beverage.
상기 S-아릴 시스테인은 IL-6 및 MCP-1 발현을 억제하는 것을 특징으로 하는 약학조성물.10. The method of claim 9,
Wherein said S-aryl cysteine inhibits IL-6 and MCP-I expression.
상기 S-아릴 시스테인은 아디포넥틴의 분비를 증가시키는 것을 특징으로 하는 약학조성물.10. The method of claim 9,
Wherein said S-arylcysteine increases the secretion of adiponectin.
상기 조성물은 캡슐, 정제, 과립, 분말 또는 음료 형태임을 특징으로 하는 약학조성물.10. The method of claim 9,
Wherein said composition is in the form of a capsule, tablet, granule, powder or beverage.
상기 대사성 질환은 당뇨, 고지혈증, 지방간, 동맥경화, 고혈압, 심혈관 질환 또는 상기 질환들이 동시다발적으로 발생하는 대사증후군으로 구성된 군으로부터 선택된 1 이상의 질환임을 특징으로 하는 약학조성물. 10. The method of claim 9,
Wherein the metabolic disease is one or more diseases selected from the group consisting of diabetes, hyperlipidemia, fatty liver, arteriosclerosis, hypertension, cardiovascular disease, or metabolic syndrome in which the diseases occur simultaneously.
상기 S-아릴 시스테인은 IL-6 및 MCP-1 발현을 억제하는 것을 특징으로 하는 건강기능식품.15. The method of claim 14,
Wherein said S-aryl cysteine inhibits IL-6 and MCP-1 expression.
상기 S-아릴 시스테인은 아디포넥틴의 분비를 증가시키는 것을 특징으로 하는 건강기능식품.15. The method of claim 14,
Wherein said S-arylcysteine increases the secretion of adiponectin.
상기 조성물은 캡슐, 정제, 과립, 분말 또는 음료 형태임을 특징으로 하는 건강기능식품.15. The method of claim 14,
Wherein said composition is in the form of a capsule, tablet, granule, powder or beverage.
상기 대사성 질환은 당뇨, 고지혈증, 지방간, 동맥경화, 고혈압, 심혈관 질환 또는 상기 질환들이 동시다발적으로 발생하는 대사증후군으로 구성된 군으로부터 선택된 1 이상의 질환임을 특징으로 하는 건강기능식품. 15. The method of claim 14,
Wherein the metabolic disease is one or more diseases selected from the group consisting of diabetes, hyperlipidemia, fatty liver, arteriosclerosis, hypertension, cardiovascular disease, or metabolic syndrome in which the diseases occur simultaneously.
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