KR20180027190A - Composition for Preventing or Treating Allergic Disease Comprising Phlorofucofuroeckol A - Google Patents
Composition for Preventing or Treating Allergic Disease Comprising Phlorofucofuroeckol A Download PDFInfo
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- KR20180027190A KR20180027190A KR1020160114482A KR20160114482A KR20180027190A KR 20180027190 A KR20180027190 A KR 20180027190A KR 1020160114482 A KR1020160114482 A KR 1020160114482A KR 20160114482 A KR20160114482 A KR 20160114482A KR 20180027190 A KR20180027190 A KR 20180027190A
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- allergic
- dermatitis
- disease
- present
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/304—Foods, ingredients or supplements having a functional effect on health having a modulation effect on allergy and risk of allergy
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Dermatology (AREA)
- Birds (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
본 발명은 플로로퓨코퓨로에콜 A 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 함유하는, 알러지성 질환의 치료 내지 개선에 효과적인 약학적 조성물, 화장료 조성물 또는 건강기능식품 조성물에 관한 것이다.The present invention relates to a pharmaceutical composition, a cosmetic composition or a health functional food composition which is effective for treating or ameliorating an allergic disease, comprising as an active ingredient flurocupurocouroecol A or a pharmaceutically acceptable salt thereof.
최근 산업발달에 따른 신규 환경오염 물질은 물론 인조섬유 등의 대량 보급에 따른 실내 생활화학 물질의 증가로 피부질환의 발병률이 크게 증가하고 있다. 특히 최근 도시인들은 생활환경이 변화함에 따라 집안의 카펫에 서식하는 진드기, 습도 저하에 따라 증가하는 먼지, 애완견의 털, 꽃가루, 새로운 과일 및 음식, 식품첨가물 등 면역 과민반응(hypersensitivity)을 유발하는 다양한 알레르겐(allergens)에 노출될 기회가 점차 커지고 있다. 이중 아토피 피부염, 천식, 알러지성 비염, 알러지성 결막염, 알러지성 피부염, 담마진 및 식품 알레르기와 같은 알러지성 질환의 발병률이 증가함에 따라 사회적인 문제로 대두되어, 이에 대한 관심이 집중되고 있다.Recently, the incidence of skin diseases has been greatly increased due to the increase of indoor living chemicals due to massive supply of artificial fibers as well as new environmental pollutants due to industrial development. In recent years, urban people have been experiencing a variety of diseases that cause immune hypersensitivity, such as ticks in the carpet of the house, dust that increases as the humidity decreases, pet hair, pollen, new fruits and food, The chance of exposure to allergens is increasing. As the incidence of allergic diseases such as atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, allergic dermatitis, chlamydia, and food allergy has increased, attention has been focused on it.
일반적으로 알러지성 질환은 면역 과민반응에 의해 발생하는 질환을 의미하는 것으로, 아토피 피부염, 천식, 알러지성 비염, 알러지성 결막염, 알러지성 피부염, 담마진 및 식품 알레르기가 포함된다.In general, allergic diseases refers to diseases caused by immune hypersensitivity reactions, including atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, dermatitis, and food allergy.
알러지성 비염은 가장 흔한 알러지성 질환으로, 발병률이 점차 증가하고 있어 생활의 질에 영향을 주고 생산능력을 감소시키며 치료비 부담을 가중시켜 사회 경제적으로 문제가 되고 있으나, 뚜렷한 치료법은 아직 없는 실정이다. 현재 사용되고 있는 치료법에는 약물요법 및 면역요법이 있는데, 약물요법은 알러지성 비염의 기본적인 치료방법이지만 약제사용 중단 시 재발이 흔하고 심각한 부작용을 일으킨다는 문제점이 있고, 면역요법은 변형된 면역체계를 원상회복 시키는 근본적인 치료를 할 수는 있지만 비용이 너무 많이 든다는 문제점이 있다.Allergic rhinitis is the most common allergic disease. Its incidence is gradually increasing, affecting the quality of life, decreasing the production capacity and increasing the burden of the treatment cost, which is a socioeconomic problem, but there is no clear treatment yet. Currently, there are drug therapy and immunotherapy. Drug therapy is the basic treatment method of allergic rhinitis. However, there is a problem that recurrence is common and serious side effects are caused when the drug is discontinued, and immunotherapy is used to restore the modified immune system to the original state However, there is a problem that the cost is too high.
한편, 천식은 알러지성 비염과 같이 대표적인 알러지성 질환으로, 기도의 만성염증으로 인해서 기도가 과민해지고 간헐적인 기도 수축이 발생하여 호흡곤란 증상을 유발하는 만성질병이다. 천식은 외부환경에 존재하는 집 먼지 진드기나 꽃가루 등의 알레르기 유발물질(알레르겐)이 원인이 되어 과도한 면역반응(알레르기반응)이 일어나 기도 점막조직에 염증이 발생하고, 이에 따라 기침, 호흡곤란 등의 천식 증상이 발생하게 된다(Lemanske RF Jr. JAMA 1997, 278, 1855-1873). 최근 면역학 및 분자유전학의 발전에 따라 천식의 병태생리에 대한 이해와 이에 따른 새로운 치료제가 개발되고 있지만, 여전히 천식 유병률은 증가하고 있는 실정이다. 특히, 기존의 치료약제로 사용되는 스테로이드제 또는 기관지 확장제는 질병의 근본적인 치유가 아닌 증상의 조절 및 예방을 위한 약제로서 이를 평생 사용해야 하기 때문에 개인 및 사회의 경제적 부담이 큰 문제가 있다. On the other hand, asthma is a typical allergic disease such as allergic rhinitis. It is a chronic disease that induces respiratory distress symptoms due to intermittent airway constriction caused by chronic inflammation of airway. Asthma is caused by allergens (allergens) such as house dust mites and pollen that are present in the external environment, resulting in an excessive immune reaction (allergic reaction) resulting in irritation of the mucosal tissues, resulting in coughing, dyspnea (Lemanske RF Jr. JAMA 1997, 278, 1855-1873). Recent developments in immunology and molecular genetics have led to the understanding of the pathophysiology of asthma and the development of new therapies, but the prevalence of asthma is still increasing. In particular, a steroid or bronchodilator used as a conventional therapeutic agent is a medicament for the control and prevention of symptoms rather than the fundamental healing of diseases, which requires a lifetime of use, resulting in a great economic burden on individuals and society.
또한, 문명병 혹은 선진국형 난치병이라고도 불리는 아토피 피부염은 어느 연령대나 발생할 수 있는 세계적으로 흔한 질병으로 70% 내지 95%는 5세 이하의 유아시기에 발병한다. 국내에서도 이미 아토피 피부염의 발병 문제가 사회적 및 의료적으로 심각한 수준에 이르고 있다. 다양한 보고에 따르면 국내 전체 국민의 약 15%가 아토피 피부염 환자이며, 이중 0 내지 4세 유아 100명당 18 내지 22명이 아토피 환자이다. 이뿐만 아니라, 아토피 피부염 환자의 50% 이상에서 알러지성 비염과 천식까지 발병하는 '아토피 행진(atopic march)' 현상도 나타나고 있다.In addition, atopic dermatitis, also called "civilized disease" or "advanced country type incurable disease," is a common worldwide disease that can occur in any age group. 70% to 95% In Korea, the onset of atopic dermatitis has already reached serious social and medical problems. According to various reports, about 15% of the total population in Korea are atopic dermatitis patients, of which 18-22 per 100 children aged 0-4 years are atopic. In addition, over 50% of patients with atopic dermatitis also develop 'atopic march' symptoms that can lead to allergic rhinitis and asthma.
상기와 같은 아토피 피부염을 비롯한 알러지성 질환의 정확한 병태생리는 아직까지 완전히 이해되고 있지 않으나, 유전적 소인과 함께 면역학적, 환경적 요인이 관여하리라고 생각되고 있으며, 특히 천식, 알러지성 비염, 아토피 피부염과 같은 알러지성 질환 환자에게서 공통적으로 면역 불균형 현상이 나타나고 있어 면역학적 관점에서 많은 연구가 이루어지고 있다.Although the exact pathophysiology of allergic diseases including atopic dermatitis as described above has not yet been fully understood, it is thought that immunological and environmental factors will be involved with genetic predisposition. In particular, asthma, allergic rhinitis, atopic dermatitis And immunologic imbalances have been common in patients with allergic diseases such as Alzheimer's disease.
한편, 알러지성 질환의 근본적인 원인은 면역 불균형으로 알려져 있는데, 이는 다양한 생물학적 신호 전달의 결과물이다. 이러한 비정상적 신호전달의 최상위 단백질이 바로 흉선 간질 림포 포이에틴(Thymic stromal lymphopoietin, TSLP) 사이토카인이다. 알레르겐이 몸에 침투되면 TSLP등의 물질이 수지상 세포를 자극하여 반응을 하는데, 이 과정에서 아토피 피부염, 천식과 같은 알러지성 질환의 증상이 나타나는 것이다.On the other hand, the underlying cause of allergic diseases is known as immune imbalance, which is the result of various biological signal transduction. Thymic stromal lymphopoietin (TSLP) cytokine is the highest protein of this abnormal signal transduction. When allergens penetrate the body, substances such as TSLP stimulate the dendritic cells to react and in this process symptoms of allergic diseases such as atopic dermatitis and asthma appear.
이러한 TSLP는 IL-7 유사 사이토카인으로 흉선 기질 세포의 배양액에서 처음 발견되었다. TSLP는 신체와 환경의 경계면(피부, 호흡기, 소화기, 안구 등)에서 면역 반응을 조절하는 중요 인자로써 피부 표피 세포, 피부 상피 세포에서 주로 분비된다. 최근 연구에 따르면, 상피 세포와 표피 각질 세포 외에도 비만세포(mast cells), 기도평활근(airway smooth muscle), 섬유아세포(fibroblasts), 수지상 세포(dendritic cells) 등에서도 TSLP가 분비되어 면역 반응을 조절하고 과발현될 경우 면역 불균형을 일으킨다고 알려졌다.These TSLPs were first found in cultures of thymus stromal cells as IL-7-like cytokines. TSLP is mainly secreted from skin epidermal cells and skin epithelial cells as an important factor controlling the immune response at the interface between the body and the environment (skin, respiratory, digestive, eye, etc.). Recent studies have shown that TSLP is secreted in mast cells, airway smooth muscle, fibroblasts, and dendritic cells in addition to epithelial and epidermal keratinocytes to regulate the immune response Overexpression is known to cause immune imbalance.
공지된 문헌에 의하면, TSLP 단백질 및 mRNA가 아토피 피부염 환자의 병소에서 증가 되어 있는 것이 발견되었으며, 피부에서 TSLP 발현을 증가시킨 인간과 동물모델(마우스)에서 심각한 알러지성 질환을 나타내었다(Steven F. Ziegler et al., J Allergy Clin Immunol, 2012; 130: 845-52). 또한 천식환자 기관지 세척액에서 TSLP가 검출되었으며, 질병의 감각성과 기도 표피세포에서 TSLP 발현 증가의 상관관계가 있음이 보고되었고 피부세포에서 분비된 TSLP 때문에 항원 노출 시 알러지성 염증반응이 심화되고 천식 발병이 촉진되는 것이 밝혀졌다(Juan et al., Journal of Investigative Dermatology, 2012).According to the known literature, TSLP protein and mRNA have been found to be increased in lesions of atopic dermatitis patients and have shown severe allergic diseases in human and animal models (mice) that have increased TSLP expression in skin (Steven F. Ziegler et al., J Allergy Clin Immunol, 2012; 130: 845-52). In addition, TSLP was detected in asthmatic patients bronchial washing solution, and there was a correlation between disease sensation and TSLP expression in airway epithelial cells. TSLP secreted from skin cells caused sensitization of allergic inflammatory reaction, (Juan et al., Journal of Investigative Dermatology, 2012).
TSLP 분비를 촉진시키는 원인으로는 바이러스(virus), 박테리아 및 박테리아 부산물(bacteria and bacterial products), 단백질 분해 효소 활성 항원(protease allergen), 염증성 사이토카인, 화학물질, 물리적 자극(긁는 행위) 등이 있으며, 과발현될 경우 면역 불균형을 일으키게 된다. 면역 불균형을 일으키는 기전은 하기 서술하는 바와 같다.Causes that promote TSLP secretion include viruses, bacteria and bacterial products, protease allergens, inflammatory cytokines, chemicals, and physical stimuli (scratching). , Overexpression causes immunological imbalance. The mechanisms causing immune imbalance are described below.
TSLP 수용체(TLSPR)는 주로 조혈세포에 발현되어 있으며, 수지상 세포(dendritic cells, DC)에 가장 많이 발현되어 있다. 수지상 세포의 생존 시간은 TSLP 때문에 증가하게 되고, 이로 인해 제II급 주조직 적합 복합체 분자(major histocompatibility complex II) 및 공자극 분자인 CD86과 CD40의 발현이 증가하며, Th2 CD4+T 세포와 나이브(naive) CD4+T 세포 유입을 각각 증가시키는 CCL17과 CCL22 분비 또한 증가하게 된다. 더욱이 Th2 분화를 증가시키는 OX40L 발현이 증가하고, Th1 분화에 관여하는 IL-12 발현이 감소하게 되어, TSLP는 결과적으로 수지상 세포가 Th2 반응을 유도하는 과정을 촉진한다. 더불어 TSLP는 호산구, 비만세포, 자연살해 T 세포의 유입 및 IL-13과 같은 사이토카인 분비를 촉진시켜 면역 불균형을 심화시킨다.The TSLP receptor (TLSPR) is mainly expressed in hematopoietic cells and is most expressed in dendritic cells (DC). The survival time of dendritic cells is increased by TSLP, leading to an increase in the expression of major histocompatibility complex II (II) and co-stimulatory molecules CD86 and CD40, and the expression of Th2 CD4 + T cells and naive and CCL17 and CCL22 secretion, which increase the number of naive CD4 + T cell inflow, respectively. Furthermore, the expression of OX40L that increases Th2 differentiation is increased, and the expression of IL-12 involved in Th1 differentiation is reduced, and TSLP consequently promotes the process of inducing Th2 response by dendritic cells. In addition, TSLP promotes the release of eosinophils, mast cells, natural killer T cells and secretion of cytokines such as IL-13, thereby exacerbating immune imbalance.
따라서 특히 TSLP와 같은 면역 불균형을 일으키는 사이토카인을 억제하여 알러지성 질환을 예방 내지 치료할 수 있는 약학 조성물 등의 개발이 시급한 실정이다.Therefore, there is an urgent need to develop a pharmaceutical composition capable of preventing or treating allergic diseases by inhibiting cytokines that cause immune imbalance such as TSLP.
본 발명의 목적은 TSLP 분비 저해능을 가짐으로써 알러지성 질환을 예방 또는 치료할 수 있는 약학적 조성물을 제공하는 것이다.It is an object of the present invention to provide a pharmaceutical composition capable of preventing or treating an allergic disease by having TSLP secretion inhibiting ability.
본 발명의 다른 목적은 TSLP 분비 저해능을 가짐으로써 알러지성 질환을 예방 또는 개선할 수 있는 화장료 조성물을 제공하는 것이다.Another object of the present invention is to provide a cosmetic composition capable of preventing or ameliorating an allergic disease by having TSLP secretion inhibiting ability.
본 발명의 또 다른 목적은 TSLP 분비 저해능을 가짐으로써 알러지성 질환을 예방 또는 개선할 수 있는 건강기능식품 조성물을 제공하는 것이다.Yet another object of the present invention is to provide a health functional food composition capable of preventing or ameliorating an allergic disease by having a TSLP secretion inhibiting ability.
본 발명은 상기 목적을 달성하기 위하여, 하기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가능한 염을 유효 성분으로 함유하는 알러지성 질환의 예방 또는 치료용 약학적 조성물을 제공한다.In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating an allergic disease, comprising a compound represented by the following general formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[화학식 1][Chemical Formula 1]
본 발명은 상기 다른 목적을 달성하기 위하여, 상기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가능한 염을 유효 성분으로 함유하는 알러지성 질환의 예방 또는 개선용 화장료 조성물을 제공한다.The present invention provides a cosmetic composition for preventing or ameliorating allergic diseases, which comprises the compound represented by the general formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명은 상기 또 다른 목적을 달성하기 위하여, 상기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가능한 염을 유효 성분으로 함유하는 알러지성 질환의 예방 또는 개선용 건강기능식품 조성물을 제공한다.The present invention provides a health functional food composition for preventing or ameliorating an allergic disease, which comprises the compound represented by the general formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명에 따르면, 플로로퓨코퓨로에콜 A 또는 이의 약학적으로 허용 가능한 염은 면역 반응 인자인 TSLP 분비를 저해하는 효과가 우수하기 때문에, 본 발명에 따른 조성물은 아토피 피부염, 천식, 알러지성 비염, 알러지성 결막염, 알러지성 피부염, 담마진 및 식품 알레르기를 포함하는 알러지성 질환의 치료제로 유용하게 적용할 수 있다.According to the present invention, since the effect of inhibiting the secretion of TSLP which is an immune response factor is excellent, the composition according to the present invention can be used for the treatment of atopic dermatitis, asthma, allergic rhinitis , Allergic conjunctivitis, allergic dermatitis, chlamydia, and food allergy.
도 1은 본 발명의 일 실시예에 따른 마우스의 귀에서 TSLP 특이적 유도제인 MC903을 이용하여 화학식 1로 표시되는 화합물의 TSLP 분비 저해 효과를 나타낸 막대그래프이다.
도 2는 본 발명의 일 실시예에 따른 IgE 유도제인 DNCB를 이용하여 화학식 1로 표시되는 화합물의 IgE 저해 효과를 나타낸 막대그래프이다.FIG. 1 is a bar graph showing the TSLP secretion inhibitory effect of a compound represented by Chemical Formula 1 using MC903, which is a TSLP-specific inducer in the ear of a mouse according to an embodiment of the present invention.
FIG. 2 is a bar graph showing the IgE inhibitory effect of the compound represented by the formula (1) using DNCB as an IgE inducer according to an embodiment of the present invention.
본 발명의 발명자들은 알러지성 질환의 효과적인 치료를 위하여, 이의 근본적인 원인인 면역 불균형을 개선할 수 있는 물질을 연구하던 중 화학식 1로 표시되는 화합물이 면역 반응을 조절하는 TSLP 분비의 과발현을 저해함으로써 면역 불균형을 해소하여 아토피 피부염, 천식, 알러지성 비염, 알러지성 결막염, 알러지성 피부염, 담마진 및 식품 알레르기와 같은 알러지성 질환을 효과적으로 완화시키는 것을 확인함으로써 본 발명을 완성하였다.The inventors of the present invention have been studying a substance capable of improving immune imbalance, which is the root cause thereof, for the effective treatment of an allergic disease, wherein the compound represented by Chemical Formula 1 inhibits overexpression of TSLP secretion controlling the immune response, The inventors have completed the present invention by confirming that the imbalance is relieved to effectively alleviate allergic diseases such as atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, chlamydia and food allergy.
따라서 본 발명은 하기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가능한 염을 유효 성분으로 함유하는 알러지성 질환의 예방 또는 치료용 약학적 조성물을 제공한다.Accordingly, the present invention provides a pharmaceutical composition for the prevention or treatment of an allergic disease comprising a compound represented by the following general formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[화학식 1][Chemical Formula 1]
상기 화학식 1로 표시되며 플로로퓨코퓨로에콜 A(phlorofurofucoeckol A)라고도 불리는 화합물은 해조류, 예컨대 곰피, 쇠미역등의 갈조류에 많이 함유되어 있어, 이로부터 추출 또는 분리하여 수득할 수 있으나, 이에 제한되지 않고 당업계에 공지된 방법에 의하여 화학적으로 합성하거나, 또는 시중에 판매되는 것을 사용할 수 있다. The compound represented by the above formula (1), which is also referred to as phlorofurofucoeckol A, is contained in seaweeds such as brown algae such as moxa and dandelion, and can be obtained by extraction or separation thereof. However, Or chemically synthesized by methods known in the art, or commercially available products can be used.
상기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가능한 염은 전체 조성물 100 중량부에 대하여 0.0001 중량부 내지 10 중량부로 포함될 수 있는 바, 상기 범위를 넘어서서 0.0001 중량부 미만으로 포함되는 경우에는 상기 화합물의 TSLP 및 IgE 분비 저해 효과가 너무 미약하게 나타나며, 10 중량부 초과로 포함되는 경우에는 함량 증가에 따른 대비 치료 효과 증가량이 적고 제형 상의 안정성이 확보되지 않는 문제점이 발생하므로 바람직하지 않다.The compound represented by Formula 1 or a pharmaceutically acceptable salt thereof may be contained in an amount of 0.0001 to 10 parts by weight based on 100 parts by weight of the total composition. When the amount of the compound is more than 0.0001 parts by weight, The TSLP and IgE secretion inhibitory effect of the composition is too weak. If the amount of the ingredient is more than 10 parts by weight, the increase of the contrast treatment effect is small and the stability of the formulation is not ensured.
이때, 본 발명에서 사용되는 용어 "TSLP(thymic stromal lymphopoietin)"는, IL-7 유사 조혈성 사이토카인으로, 상피세포, 기질세포 및 비만세포에서 생성되며 인체의 면역 반응을 조절하는 중요한 인자이다. 따라서 TSLP가 피부 세포를 포함하여 인체 내에서 과발현(과분비)될 경우 면역 불균형을 초래하고, 이에 따라 알러지성 질환의 발병 개시 및 심화를 유발한다. As used herein, the term " thymic stromal lymphopoietin "(TSLP) is an IL-7-like hematopoietic cytokine, which is produced in epithelial cells, stromal cells and mast cells and is an important factor controlling the immune response of the human body. Thus, overexpression (hypersecretion) of TSLP, including skin cells, in the human body leads to immune imbalance, thereby causing initiation and intensification of the onset of allergic diseases.
본 발명의 일 실시예에 따르면, TSLP 특이적 유도제인 MC903를 처리한 마우스 귀에 상기 화학식 1로 표시되는 화합물을 처리한 결과 상기 화학식 1로 표시되는 화합물이 TSLP 분비를 저해하는 것을 확인하였고, 2,4-디니트로클로로벤젠(2,4-dinitrochlorobenzene, DNCB)를 처리한 마우스에서는 상기 화학식 1로 표시되는 화합물이 IgE를 저해하는 것을 확인할 수 있었다.According to one embodiment of the present invention, the compound represented by Formula 1 was treated with the compound of
즉, 상기 조성물은 TSLP 및 IgE 분비 저해 효과를 보이므로, 면역 불균형에 의해 유발되는 알러지성 질환의 예방 또는 치료능을 가질 수 있다.That is, since the composition exhibits TSLP and IgE secretion inhibiting effects, it can have the ability to prevent or treat allergic diseases caused by immune imbalance.
또한, 본 발명에서 사용되는 용어 "알러지성 질환(Allergic disease)"은, 알러지성 소인, 즉, 알러지 반응(면역과민반응)에 의해서 발증하는 질환을 의미한다. 아직까지 정확한 발병원인이 밝혀지진 않았으나, 대부분의 알러지성질환 환자에게서 면역 불균형이 관찰되고 있어 면역 불균형 조절을 통한 치료제 또는 치료방법이 활발히 연구되고 있다.The term "Allergic disease " used in the present invention means a disease caused by an allergic disease, that is, an allergic reaction (immunosuppressive reaction). Although the precise cause of the disease has not yet been elucidated, immune imbalance has been observed in most allergic diseases, and therapeutic agents or methods for treatment of immune imbalance have been actively studied.
본 발명에서, 이러한 알러지성 질환은 아토피 피부염(atopic dermatitis), 천식(asthma), 알러지성 비염(allergic rhinitis), 알러지성 결막염(allergic conjunctivitis), 알러지성 피부염(allergic dermatitis), 담마진(두드러기, hives) 및 식품 알레르기(food allergy)로 이루어진 군에서 선택되는 하나 이상일 수 있으나, 이에 제한되는 것은 아니다.In the present invention, such allergic diseases include atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, urticaria, hives ) And food allergy, but the present invention is not limited thereto.
구체적으로, 본 발명의 상기 아토피 피부염은, 주로 유아기 혹은 소아기에 시작되는 만성적 재발성의 염증성 피부질환으로 소양증(가려움증)과 피부건조증, 특징적인 습진을 동반하는 질환이다.Specifically, the atopic dermatitis of the present invention is a chronic recurrent inflammatory skin disease which is mainly in infancy or childhood, and is a disease accompanied by pruritus (itching), dry skin and characteristic eczema.
본 발명의 상기 천식은, 폐 속에 있는 기관지가 아주 예민해진 상태, 즉 때때로 기관지가 좁아져서 숨이 차고 가랑가랑하는 숨소리가 들리면서 기침을 심하게 하는 증상을 나타내는 질환으로, 기관지의 알레르기 염증 때문에 발생하는 알러지성 질환이다.The asthma of the present invention is a condition in which the bronchus in the lung is very sensitive, that is, the bronchus is narrowed, and the breathing and cramping breath sounds are heard and the cough is severe. It is an allergic disease.
본 발명의 상기 알러지성 비염은, 코 점막이 특정 물질에 대하여 과민반응을 나타내는 것으로 알레르기를 일으키는 원인 물질(항원)이 코 점막에 노출된 후 자극 부위로 비만세포, 호산구를 비롯한 여러 종류의 IgE 항체를 매개로 하는 염증세포가 몰려들어 이들이 분비하는 다양한 매개물질에 의하여 염증반응이 발생하는 질환을 의미한다.The above-mentioned allergic rhinitis of the present invention indicates that the nasal mucosa exhibits an hypersensitivity reaction to a specific substance. After the causative substance (antigen) causing the allergy is exposed to the nasal mucosa, various kinds of IgE antibodies including mast cells, eosinophils Inflammatory cells mediate the inflammatory reaction caused by various mediators secreted by these means.
본 발명의 상기 알러지성 결막염은, 국소 감각에 의해 생기는 결막염을 의미하는 것으로, 결막의 가벼운 충혈만 있는 것에서부터 안검종창, 결막부종을 수반하는 것까지 있으며, 특히 유전성 소인에 관련이 있고 즉시형 알러지를 나타내는 것을 알러지성 결막염이라고 한다.The allergic conjunctivitis of the present invention refers to a conjunctivitis caused by a local sensation, including conjunctival mild conjunctivitis, accompanied by swollen eyelid swelling and conjunctival swelling, particularly related to genetic susceptibility, Is referred to as allergic conjunctivitis.
본 발명의 상기 알러지성 피부염은, 알러지를 일으키는 물질에 대한 면역과민 반응으로 피부에 염증이 생기는 증상을 나타내는 질환을 의미한다.The allergic dermatitis of the present invention refers to a disease that manifests symptoms of inflammation of the skin due to immunological hypersensitivity to allergen-causing substances.
본 발명의 상기 담마진(두드러기)은, 피부나 점막에 존재하는 혈관의 투과성이 증가하면서 일시적으로 혈장 성분이 조직 내에 축적되어 피부가 붉거나 흰색으로 부풀어 오르고 심한 가려움증이 동반되는 피부 질환을 의미한다.The urticaria (urticaria) of the present invention refers to a skin disease in which permeability of blood vessels existing in the skin or mucous membranes is increased, and plasma components are temporarily accumulated in the tissues to swell the skin red or white, accompanied by severe itching.
본 발명의 상기 식품 알레르기는, 음식물에 의해 일어나는 알레르기 반응으로, 대부분 알레르기 반응을 일으키는 식품(가성 알레르겐)을 섭취한 후 바로 증세가 나타나거나, 수 시간 경과 후에 나타나는 경우도 있다.The food allergy of the present invention is an allergic reaction caused by food or food, and the symptoms may appear immediately after ingesting a food (a pseudo-allergen) that causes most of the allergic reaction, or may appear after a lapse of several hours.
본 발명에서 사용되는 용어 "예방"은, 상기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가능한 염을 함유하는 조성물의 투여로 질환을 억제 또는 지연시키는 모든 행위를 의미한다. 또한, 본 발명에서 사용되는 용어 "치료"는, 상기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가능한 염을 함유하는 조성물의 투여로 질환의 증세가 호전되거나 완치되는 모든 행위를 의미한다.The term "prophylactic " as used in the present invention means any action which inhibits or delays disease by the administration of a composition containing the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof. The term "treatment" used in the present invention means all the actions of improving or ameliorating symptoms of a disease by administration of a composition containing the compound represented by the above-mentioned formula (1) or a pharmaceutically acceptable salt thereof.
본 발명의 화학식 1로 표시되는 화합물은 약학적으로 허용되는 염의 형태로 사용될 수 있으며, 이러한 염으로는 약학적으로 허용되는 유리산(free acid)에 의해 형성되는 산부가염 또는 염기에 의해 형성되는 금속염이 있다. 상기 유리산으로는 무기산과 유기산이 사용될 수 있으며, 무기산으로는 염산, 황산, 브롬산, 아황산 또는 인산 등이 사용될 수 있다. 상기 금속염으로는 알칼리 금속염 또는 알칼리 토금속염이 있으며, 나트륨, 칼륨 또는 칼슘염이 유용하다.The compound represented by formula (1) of the present invention can be used in the form of a pharmaceutically acceptable salt. Examples of such salts include acid addition salts formed by pharmaceutically acceptable free acids or metal salts formed by a base . As the free acid, an inorganic acid and an organic acid may be used. As the inorganic acid, hydrochloric acid, sulfuric acid, bromic acid, sulfurous acid, phosphoric acid or the like may be used. The metal salts include alkali metal salts or alkaline earth metal salts, and sodium, potassium or calcium salts are useful.
본 발명의 조성물은 투여를 위하여, 상기 기재한 유효성분 이외에 약학적으로 허용 가능한 담체, 부형제 또는 희석제를 포함할 수 있다. 상기 담체, 부형제 및 희석제로는 락토오스, 덱스트로오스, 수크로오스, 소르비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로오스, 미정질 셀룰로오스, 폴리비닐피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다.The composition of the present invention may contain, for administration, a pharmaceutically acceptable carrier, excipient or diluent in addition to the above-described effective ingredients. Examples of the carrier, excipient and diluent 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.
본 발명의 약학적 조성물은 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 또는 멸균 주사용액의 형태로 제형화하여 사용할 수 있다. 상세하게는 제형화할 경우 통상 사용하는 충진제, 중량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 경구투여를 위한 고형 제제로는 정제, 환제, 산제, 과립제, 캡슐제 등을 포함하나, 이에 한정되는 것은 아니다. 이러한 고형 제제는 상기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가능한 염에 적어도 하나 이상의 부형제, 예를 들면, 전분, 칼슘 카보네이트, 수크로오스, 락토오스, 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용될 수 있다. 경구를 위한 액상물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등을 첨가하여 조제될 수 있다. 비경구 투여를 위한 제제는 멸균된 수용액, 비수성 용제, 현탁제, 유제, 동결건조 제제 및 과제를 포함한다. 비수성 용제 및 현탁제로는 프로필렌글리콜, 폴리에틸렌글리콜, 올리브 오일과 같은 식물성 오일, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔, 마크로솔, 트윈 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있다.The pharmaceutical compositions of 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. In detail, when formulating, it can be prepared using diluents or excipients such as fillers, weights, binders, humectants, disintegrants, surfactants and the like which are usually used. Solid form preparations for oral administration include, but are not limited to, tablets, pills, powders, granules, capsules and the like. Such a solid preparation can be prepared by mixing at least one or more excipients such as starch, calcium carbonate, sucrose, lactose, gelatin and the like in the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration, liquid paraffin, and various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and tasks. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like. As a base for suppositories, it is possible to use witepsol, macrosole, tween 61, cacao paper, laurin, glycerogelatin and the like.
본 발명의 조성물의 적합한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 시간에 따라 다르지만, 당 업자에 의해 적절하게 선택될 수 있는 바, 상기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가능한 염의 일일 투여량은 바람직하게는 1 mg/kg 내지 500 mg/kg이며, 필요에 따라 일일 1회 내지 수회로 나누어 투여할 수 있다.A suitable dose of the composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, and the time, but can be appropriately selected by the skilled person. Is preferably 1 mg / kg to 500 mg / kg, and may be administered once or several times a day, if necessary.
본 발명은 또한, 하기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 함유하는 알러지성 질환의 예방 또는 개선용 화장료 조성물을 제공한다.The present invention also provides a cosmetic composition for preventing or ameliorating an allergic disease comprising a compound represented by the following general formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[화학식 1][Chemical Formula 1]
종래 알려진 바에 의하면, TSLP가 인간 및 동물의 피부에 과발현될 경우 심각한 알러지성 질환(아토피 피부염, 천식, 알러지성 비염, 알러지성 결막염, 알러지성 피부염 또는 담마진 등)을 유발할 수 있으며, 알러지성 피부 염증(아토피 피부염 등)의 개시 및 진행에 영향을 줄 수 있다(Steven F. Ziegler et al., J Allergy Clin Immunol, 2012; 130: 845-52). 또한 피부 세포에서 분비된 TSLP에 의하여 항원 노출시 알러지성 염증반응이 심화되고 천식 발병이 촉진된다(Juan et al., Journal of Investigative Dermatology, 2012). It has been known that when TSLP is over-expressed in human and animal skin, it can cause severe allergic diseases (atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis or dermatitis) (Steven F. Ziegler et al., J Allergy Clin Immunol, 2012; 130: 845-52). In addition, TSLP secreted from skin cells induces an allergic inflammatory response and accelerates the onset of asthma when exposed to antigens (Juan et al., Journal of Investigative Dermatology, 2012).
따라서, 본 발명의 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 함유하는 화장료 조성물은, 피부에서의 TSLP의 과발현을 저해할 수 있는 바, 이때 상기 알러지성 질환은 아토피 피부염, 천식, 알러지성 비염, 알러지성 결막염, 알러지성 피부염, 담마진 및 식품 알레르기로 이루어진 군에서 선택되는 하나 이상일 수 있다.Therefore, the cosmetic composition containing the compound represented by the formula (I) of the present invention or a pharmaceutically acceptable salt thereof as an active ingredient can inhibit overexpression of TSLP in the skin, wherein the allergic disease is atopic dermatitis , Asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, dermatitis, and food allergy.
본 발명의 화장료 조성물은 상기 유효성분 이외에 통상적으로 허용되는 성분들을 포함할 수 있으며, 예컨대 항산화제, 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제, 그리고 담체를 포함할 수 있다.The cosmetic composition of the present invention may contain ingredients generally accepted in addition to the above-mentioned effective ingredients, and may include conventional additives such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavors, and carriers.
본 발명의 화장료 조성물은 당업계에서 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있으며, 예를 들어, 용액, 현탁액, 유탁액, 페이스트, 겔, 크림, 로션, 파우더, 비누, 계면활성제-함유 클렌징, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션 및 스프레이 등으로 제형화될 수 있으나, 이에 제한되는 것은 아니다. 보다 상세하게는, 유연 화장수(스킨), 영양 화장수(밀크로션), 영양크림, 마사지크림, 에센스, 아이크림, 클렌징 크림, 클렌징 폼, 클렌징 워터, 팩, 스프레이 또는 파우더의 제형으로 제조될 수 있다.The cosmetic composition of the present invention can be prepared into any of the formulations conventionally produced in the art and can be used in the form of solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, , Oil, powdered foundation, emulsion foundation, wax foundation and spray, but is not limited thereto. More specifically, it can be manufactured in the form of a flexible lotion (skin), a nutritional lotion (milk lotion), a nutritional cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray or a powder .
본 발명의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물성 오일, 식물성 오일, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연등이 이용될 수 있다.When the formulation of the present invention is a paste, cream or gel, an animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier component .
본 발명의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴라아미드 파우더가 이용될 수 있으며, 특히 스프레이인 경우에는 추가적으로 클로로 플루오로 히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다.When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or a polyamide powder may be used as a carrier component. In the case of a spray, in particular, chlorofluorohydrocarbons, propane / Propane or dimethyl ether.
본 발명의 제형이 용액 또는 유탁액인 경우에는 담체 성분으로서 용매, 용해화제 또는 유탁화제가 이용되고, 예로서 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌글리콜, 1,3-부틸글리콜 오일, 글리세롤지방족에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르를 들 수 있다.When the formulation of the present invention is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or fatty acid esters of sorbitan.
본 발명의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌글리콜과 같은 액상의 희석제, 에톡실화이소스테아릴 알코올, 폴리옥시에틸렌소르비톨에스테르 및 폴리옥시에틸렌소르비탄에스테르와 같은 현탁제, 미소 결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 이용될 수 있다.In the case where the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.
본 발명의 제형이 계면-활성제 함유 클렌징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시테이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성 오일, 라놀린 유도체 또는 에톡실화글리세롤 지방산 에스테르 등이 이용될 수 있다.When the formulation of the present invention is an interface-active agent-containing cleansing, the carrier component is selected from the group consisting of aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters.
또한, 본 발명은 하기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가능한 염을 유효 성분으로 함유하는 알러지성 질환의 예방 또는 개선용 건강기능식품 조성물을 제공한다.The present invention also provides a health functional food composition for preventing or ameliorating an allergic disease, comprising a compound represented by the following general formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[화학식 1][Chemical Formula 1]
이때 상기 알러지성 질환은 아토피 피부염, 천식, 알러지성 비염, 알러지성 결막염, 알러지성 피부염, 담마진 및 식품 알레르기로 이루어진 군에서 선택되는 하나 이상일 수 있다.At this time, the allergic disease may be at least one selected from the group consisting of atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, dermatitis, and food allergy.
상기 건강기능식품 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, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 천연 과일 주스, 합성 과일 주스 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 또한, 건강기능식품 조성물은 육류, 소세지, 빵, 초콜릿, 캔디류, 스넥류, 과자류, 피자, 라면, 껌류, 아이스크림류, 스프, 음료수, 차, 기능수, 드링크제, 알코올 및 비타민 복합제 중 어느 하나의 형태일 수 있다.The health functional food composition may contain various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and heavies (cheese, chocolate etc.), pectic acid and its salts, alginic acid and its salts , Organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. It may also contain flesh for the production of natural fruit juices, synthetic fruit juices and vegetable drinks. These components may be used independently or in combination. The health functional food composition may be in the form of any one of meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, gum, ice cream, soup, beverage, tea, functional water, drink, alcohol and vitamin complex Lt; / RTI >
또한, 상기 건강기능식품 조성물은 식품첨가물을 추가로 포함할 수 있으며, "식품첨가물"로서의 적합 여부는 다른 규정이 없는 한 식품의약품 안정청에 승인된 식품첨가물공전의 총칙 및 일반 시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다.In addition, the health functional food composition may further include a food additive, and the suitability of the food functional additive as a "food additive" Of the present invention.
상기 "식품첨가물공전"에 수재된 품목으로 예를 들어, 케톤류, 글리신, 구연산 칼륨, 니코틴산, 계피산 등의 화학적 합성품, 감색소, 감초추출물, 결정셀룰로오스, 고랭색소, 구아검 등의 천연첨가물, L-글루타민산나트륨 제제, 면류 첨가 알칼리제, 보존 료제제, 타르색소 제제 등의 혼합 제제류 등을 들 수 있다.Examples of the products that have been used in the above-mentioned "food additives" include natural products such as ketones, chemical products such as glycine, potassium citrate, nicotinic acid and cinnamic acid, sensory coloring matter, licorice extract, crystalline cellulose, high- - Mixed preparations such as a sodium glutamate preparation, a noodle-added alkaline agent, a preservative preparation, and a tar coloring agent.
이때, 건강기능식품 조성물을 제조하는 과정에서 식품에 첨가되는 본 발명에 따른 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가능한 염은 필요에 따라 그 함량을 적절히 가감할 수 있으며, 바람직하게는 식품 100 중량부에 1 중량부 내지 15 중량부 포함되도록 첨가하는 것이 바람직하다.Herein, the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof according to the present invention, which is added to the food during the production of the health functional food composition, can be appropriately added or decreased as needed, 1 part by weight to 15 parts by weight to 100 parts by weight.
이하, 본 발명의 이해를 돕기 위하여 실시예를 들어 상세하게 설명하기로 한다. 다만 하기의 실시예는 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이며, 본 발명의 내용을 예시하는 것일 뿐이므로 본 발명의 범위가 하기 실시예에 한정되는 것은 아니다.BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. It is to be understood, however, that these examples are provided for the purpose of providing a more complete understanding of the present invention to those skilled in the art, and that the scope of the present invention is limited only by the following examples It is not.
<< 실시예Example 1> 화학식 1로 표시되는 화합물인 1 > The compound represented by formula 플로로퓨코퓨로엑콜≪ RTI ID = 0.0 > A(phlororofucofuroeckol A)의 동물실험 효과 Effects of A (phlororofucofuroeckol A)
먼저 본 발명의 화학식 1로 표시되는 화합물 플로로퓨코퓨로엑콜 A(phlororofucofuroeckol A)는 한밭대학교 이봉호 교수님에게서 받아 사용하였다. 이후, 플로로퓨코퓨로엑콜 A(phlororofucofuroeckol A)의 동물실험 효과를 분석하기 위하여, TSLP 유도제인 MC903 4 nmole 과 플로로퓨코퓨로엑콜 A(phlororofucofuroeckol A) 1%를 생쥐 귀에 3일 동안 도포한 후, 귀 조직을 RIPA 완충 용액을 이용하여 파쇄하여 균질 현탁액을 취하여 ELISA 방법으로 TSLP 농도를 측정하였다. 구체적인 ELISA 방법은 R&D systems(Minneapolis, MN, USA)의 제공된 프로토콜을 따랐다. 또한 MC903 및 플로로퓨코퓨로엑콜 A를 처리하지 않은 대조군과 MC903만을 처리한 대조군의 TSLP 농도를 동일한 방법으로 측정하였다.First, the compound of formula (1) of the present invention, phlororofucofuroeckol A, was obtained from Professor Lee Bongho of Hanbat National University. To analyze the effect of phlororofucofuroeckol A in animals, 4 nmole of the TSLP inducer MC903 and 1% of phlororofucofuroeckol A were applied to the mouse ear for 3 days After that, ear tissues were disrupted using RIPA buffer, and the homogenous suspension was taken and TSLP concentration was measured by ELISA method. The specific ELISA method followed the protocol provided by R & D systems (Minneapolis, MN, USA). In addition, the concentration of TSLP in the control group treated with MC903 and the control group treated with MC903 alone was measured by the same method.
그 결과, 도 1에 나타난 바와 같이, 본 발명의 화학식 1로 표시되는 화합물인 플로로퓨코퓨로엑콜 A(phlororofucofuroeckol A)가 동물실험에서 TSLP 분비 저해능을 나타내었다. 이는, 상기 플로로퓨코퓨로엑콜 A(phlororofucofuroeckol A)가 동물이나 사람에서도 TSLP 분비를 효과적으로 저해함으로써 면역 조절 효과를 가져 면역 불균형을 해소할 수 있음을 의미한다.As a result, as shown in FIG. 1, phlororofucofuroeckol A, which is a compound represented by
<< 실시예Example 2> 2> balbbalb /c 마우스의 / c of the mouse DNCB에On DNCB 의해 유도된 염증 세포의 침윤 및 Infiltration of inflammatory cells induced by IgEIgE 유리에 대한 플로로퓨코퓨로엑콜 A(phlororofucofuroeckol A)의 효과 Effect of phlororofucofuroeckol A on glass
비만 세포(Mast cells)는 IgE 매개 알러지성 질환의 중요한 작용기로 알려져 있으며, 혈청 내 IgE 레벨의 증가는 아토피성 피부염의 중요한 특징이다. 이에, 화학식 1로 표시되는 플로로퓨코퓨로에콜 A의 아토피성 피부염의 치료 효능을 알아보기 위해, 1% 2,4-디니트로클로로벤젠(2,4-dinitroochlorobenzene, DNCB) 및 실시예 1에서 준비한 플로로퓨코퓨로에콜 A 1%를 balb/c 마우스에 귀에 50 ㎕만큼 1주일 동안 격일로 3회 처리한 후, 귀 조직을 RIPA 완충 용액을 이용해 파쇄하였다. 이때 얻은 균질 현탁액의 IgE 농도를 eBIO Science(San Diego, CA, USA)에서 구입한 IgE ELISA kit을 이용하여 eBIO Science에서 제공한 방법을 따라 측정하였다. 또한, DNCB 및 플로로퓨코퓨로에콜 A를 처리하지 않은 대조군과 DNCB만을 처리한 대조군의 IgE 농도를 동일한 방법으로 측정하였다.Mast cells are known to be an important functional group of IgE mediated allergic diseases, and the increase in serum IgE levels is an important feature of atopic dermatitis. In order to examine the therapeutic effect of atropic dermatitis of the fluorophosphoric acid A represented by the formula (1), 1% 2,4-dinitrochlorobenzene (DNCB) and 1% 1% of the prepared flurocoupuropaecol A was treated with balb / c mice three times a day for one week as much as 50 μl in the ear, and then the ear tissue was disrupted using RIPA buffer solution. The IgE concentration of the obtained homogeneous suspension was measured using the IgE ELISA kit purchased from eBIO Science (San Diego, Calif., USA) according to the method provided by eBIO Science. In addition, the IgE concentrations of the control group not treated with DNCB and fluorophosphoroechoic A and the control group treated with DNCB alone were measured by the same method.
그 결과, 도 2에 나타난 바와 같이, 화학식 1로 표시되는 화합물을 처리하지 않은 대조군들에서 DNCB의 처리는 정상 마우스에 비교하였을 때 혈청 내 IgE 레벨을 상당히 증가시킨 반면, 플로로퓨코퓨로엑콜 A(phlororofucofuroeckol A)를 처리한 군은 IgE 레벨이 상당히 감소된 것을 확인하였다.As a result, as shown in Fig. 2, the treatment of DNCB in the control groups not treated with the compound represented by the formula (1) significantly increased the IgE level in the serum when compared to the normal mouse, while the concentration of the fluorophosphoric acid A (phlororofucofuroeckol A) treated group significantly decreased the IgE level.
이상으로 본 발명의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적 기술은 단지 바람직한 실시예일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백할 것이다. 따라서, 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의하여 정의된다고 할 것이다.While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that such detail is solved by the person skilled in the art without departing from the scope of the invention. will be. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.
Claims (8)
[화학식 1]
[Chemical Formula 1]
[화학식 1]
[Chemical Formula 1]
[화학식 1]
[Chemical Formula 1]
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