KR20230025253A - Composition for preventing or treating atopic dermatitis comprising loliolide - Google Patents
Composition for preventing or treating atopic dermatitis comprising loliolide Download PDFInfo
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- KR20230025253A KR20230025253A KR1020210107552A KR20210107552A KR20230025253A KR 20230025253 A KR20230025253 A KR 20230025253A KR 1020210107552 A KR1020210107552 A KR 1020210107552A KR 20210107552 A KR20210107552 A KR 20210107552A KR 20230025253 A KR20230025253 A KR 20230025253A
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- KR
- South Korea
- Prior art keywords
- atopic dermatitis
- skin
- loliolide
- preventing
- present
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- 201000008937 atopic dermatitis Diseases 0.000 title claims abstract description 62
- 206010012438 Dermatitis atopic Diseases 0.000 title claims abstract description 61
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Images
Classifications
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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
- A61K31/365—Lactones
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/02—Algae
- A61K36/03—Phaeophycota or phaeophyta (brown algae), e.g. Fucus
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
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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
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A—HUMAN NECESSITIES
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- A23V2250/00—Food ingredients
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Abstract
Description
본 발명은 롤리올라이드(loliolide)를 포함하는 조성물에 관한 것이다.The present invention relates to compositions comprising loliolide.
인체의 피부는 외부환경으로부터 생체를 보호하는 보호막의 기능을 하는 기관으로서, 인체 내의 물, 전해질 등의 생체 성분의 손실을 방지하며, 동시에 외부로부터 유해물질의 침입을 막는 역할을 한다. 피부의 구조는 크게 표피층, 피층 및 피하지방으로 구분된다. 표피층은 각질세포와 멜라닌 세포로 구성되는데, 피부 최외각의 각질 세포층은 외부 환경과 직접 접촉하기 때문에 물리적, 화학적 혹은 물질의 투과에 대한 1차 방어막으로 작용한다. 또한 피부 외부로 수분 손실을 막음과 동시에 자체적으로 세포 간지질을 라멜라층으로 형성하여 자체수분을 보유함으로써 유연성의 유지 또한 요구된다. 각질층의 중요성이 강조됨에 따라 이에 대한 연구가 활발하게 이루어지고 있으며, 특히 각질층 내에 존재하는 각질세포간 지질의 구조와 기능 등에 대한 연구가 활발하게 이루어지고 있다. 각질 세포간 지질은 라멜라 구조로 명명되는 여러 층의 지질막 형태를 나타내며, 특히 세라마이드 성분이 각질세포간 지질의 기능에 중요한 역할을 하는 것으로 알려지면서 이를 활용한 다양한 보습제 등이 개발되고 있다.The skin of the human body is an organ that functions as a protective film that protects the living body from the external environment, and prevents the loss of biological components such as water and electrolytes in the human body, and at the same time prevents the intrusion of harmful substances from the outside. The structure of the skin is largely divided into the epidermal layer, cortical layer, and subcutaneous fat. The epidermal layer is composed of keratinocytes and melanocytes. The outermost keratinocyte layer of the skin directly contacts the external environment and acts as a primary barrier against permeation of physical, chemical or substances. In addition, it is also required to maintain flexibility by preventing water loss to the outside of the skin and at the same time forming intercellular lipid into a lamellar layer to retain its own water. As the importance of the stratum corneum is emphasized, research on this has been actively conducted, and in particular, studies on the structure and function of lipids between keratinocytes present in the stratum corneum have been actively conducted. Keratinocyte intercellular lipids represent the form of several layers of lipid membranes called lamellar structures, and in particular, as ceramide components are known to play an important role in the function of interkeratinocyte lipids, various moisturizers using them are being developed.
한편, 아토피 피부염(atopic dermatitis)의 기전을 이해하는 데에는 면역학적 이상, 특히 Th2 면역 반응이 관여하는 염증에 기인한다는 의견이 우세하였으나, 최근에는 아토피 피부염을 표피 투과 및 항균 장벽 기능의 손상에 의한 일차적인 피부 장벽의 이상에 의한 것이라는 의견이 제시되고 있다. 즉, 아토피 피부염 환자의 피부는 유전적인 이상 및 피부 장벽을 구성하는 세라마이드 등의 지질 이상으로 표피의 수분 함유량 감소 및 피부 장벽이 기능 이상이 유발된다. 이로 인해 항원의 피부 침투가 증가하게 되고, 면역반응이 증가하며, 세정제의 사용 등에 의한 피부 pH 변화 등의 다양한 악화 요인이 피부 장벽의 악화를 심화시키게 된다.On the other hand, in understanding the mechanism of atopic dermatitis, the prevailing view is that it is due to immunological abnormalities, especially inflammation involving the Th2 immune response, but recently, atopic dermatitis has been identified as primary due to epidermal permeation and damage to the antibacterial barrier function. Opinions have been suggested that it is caused by abnormalities in the bast barrier. That is, in the skin of patients with atopic dermatitis, a decrease in the moisture content of the epidermis and a functional abnormality of the skin barrier are caused by genetic abnormalities and lipid abnormalities such as ceramide constituting the skin barrier. As a result, skin penetration of antigens increases, immune responses increase, and various deteriorating factors such as skin pH change due to the use of detergents intensify deterioration of the skin barrier.
아토피 피부염은 가려움증, 피부 건조증, 습진 등을 동반하는 염증성 질환 또는 유전적, 환경적, 면역학적 원인으로 인하여 피부의 가장 바깥에 위치한 피부 보호벽인 각질층에 이상이 생겨서 발생하는 질환으로 건조한 기후에서는 더욱 심해지는 경향이 있다. 이러한 아토피 피부염은 다양한 원인이 복합하게 뒤엉켜 발생하고 완화와 재발을 반복한다. 아토피 소인에 의한 알레르기 질환으로 알레르기성 피부염, 알레르기성 비염, 천식, 알레르기성 결막염, 아토피성 두드러기 등이 있으며, 이들 질환은 단독으로 또는 다른 질환과 동시에 나타날 수 있다. 아토피 피부염은 상당히 많은 사람들이 앓고 있는데, 전 인구의 0.5~1%, 어린이의 경우 5~10%가 아토피 피부염으로 고통받고 있다. 환자의 50%는 두 돌 이내에 치유되나 25%는 청소년기까지 이어지며, 나머지 25%는 성인이 되어도 아토피 피부염이 없어지지 않고 계속된다.Atopic dermatitis is an inflammatory disease accompanied by itching, skin dryness, eczema, etc., or a disease caused by abnormalities in the stratum corneum, the outermost layer of the skin, due to genetic, environmental, or immunological causes. It is more severe in dry climates. tends to Such atopic dermatitis is caused by a complex entanglement of various causes, and remission and recurrence are repeated. Allergic diseases caused by atopic predisposition include allergic dermatitis, allergic rhinitis, asthma, allergic conjunctivitis, and atopic urticaria, and these diseases may appear alone or simultaneously with other diseases. Atopic dermatitis is suffering from a significant number of people, 0.5 to 1% of the entire population, and 5 to 10% of children suffer from atopic dermatitis. 50% of patients are cured within two years, but 25% continue into adolescence, and the remaining 25% continue to have atopic dermatitis even into adulthood.
아토피 체질은 근본적으로 치료하기 매우 어려우므로 아토피 피부염은 완치를 목표로 하기 보다는 유발 인자를 피하고 적절한 치료를 통해 조절해 나가고 있다. 현재 사용되고 있는 일반적인 아토피 피부염 증산 완화제로는 보습제, 소양증(가려움증)을 감소시켜주는 항히스타민제, 항염증, 혈관수축, 면역 억제 작용을 통해 치료 효과를 보는 국소 스테로이드제 등이 있으며, 아토피 피부염에 대한 처방은 이러한 스테로이드제, 항히스타민제, 항생제 등과 같은 약물요법이 주로 이루어지고 있다. 스테로이드 계열의 글루코코르티코이드(Glucocorticoid), 사이클로스포린(Cyclospoline) 등의 약물은 당뇨병, 고혈압을 유발시킬 수 있으며 쿠싱 증후군, 안과질환(백내장, 녹내장), 신장, 간 독성이 생기는 등 심각한 부작용을 초래한다. 특히, 스테로이드제(부신피질호르몬제)는 크게 소염작용과 면역억제 작용이 있으며 효과가 우수하지만, 장기간 바르면 피부약화, 전신 호르몬 증상, 중독성 등의 부작용이 나타날 수 있다. 항히스타민제는 비만세포에서 히스타민이 유리되지 못하도록 하여 가려운 증상을 경감시키지만, 임시방편으로 이용되는 것으로서, 장기간 복용 시에는 불면, 불안, 식욕감퇴 등의 부작용이 있을 수 있다.Since atopic constitution is fundamentally very difficult to treat, atopic dermatitis is being controlled through appropriate treatment by avoiding triggers rather than aiming for complete cure. Common atopic dermatitis transpiration agents that are currently used include moisturizers, antihistamines that reduce pruritus (itching), topical steroids that have therapeutic effects through anti-inflammatory, vasoconstrictor, and immunosuppressive actions, and are prescribed for atopic dermatitis. Drug therapy such as steroids, antihistamines, and antibiotics is mainly used. Steroid drugs such as glucocorticoid and cyclosporine can cause diabetes and high blood pressure, and cause serious side effects such as Cushing's syndrome, eye disease (cataract, glaucoma), kidney and liver toxicity. In particular, steroids (adrenocortical hormones) have anti-inflammatory and immunosuppressive effects and are highly effective, but when applied for a long time, side effects such as skin weakening, systemic hormone symptoms, and addiction may appear. Antihistamines reduce the itching symptoms by preventing histamine from being released from mast cells, but are used as a temporary measure, and may have side effects such as insomnia, anxiety, and loss of appetite when taken for a long time.
이에, 아토피 피부염에 효과가 있으면서도 부작용이 없는 새로운 개념의 아토피 피부염 치료제가 요구되고 있다.Accordingly, there is a demand for a new concept of atopic dermatitis treatment that is effective for atopic dermatitis and has no side effects.
롤리올라이드에 대하여는 아세틸콜린에스테라아제(acetylcholinesterase)의 활성을 억제(Fang, Z. et al., Chem Pharm Bull(Tokyo)., 58(9), 1236-1239, 2010)하고, 인간 대장암세포주인 Caco-2에서의 항증식 활성(Machado, F. B. et al., Molecules, 17(2), 1852-1859, 2012)에 대해 보고된 바 있으나, 아토피 피부염과 관련한 약리효능에 대하여는 알려진 바가 없다.Roliolide inhibits the activity of acetylcholinesterase (Fang, Z. et al., Chem Pharm Bull (Tokyo)., 58(9), 1236-1239, 2010), and human colorectal cancer cell line Caco Antiproliferative activity in -2 (Machado, F. B. et al., Molecules, 17(2), 1852-1859, 2012) has been reported, but pharmacological effects related to atopic dermatitis are not known.
일 구체예에 따르면 롤리올라이드를 유효성분으로 포함하는 아토피 피부염 예방 또는 치료용 약학적 조성물을 제공한다.According to one embodiment, a pharmaceutical composition for preventing or treating atopic dermatitis containing roliolide as an active ingredient is provided.
다른 구체예에 따르면 롤리올라이드를 포함하는 아토피 피부염의 예방 또는 개선용 식품 조성물을 제공한다.According to another embodiment, a food composition for preventing or improving atopic dermatitis containing roliolide is provided.
또 다른 구체예에 따르면 롤리올라이드를 포함하는 아토피 피부염의 예방 또는 개선용 화장품 조성물을 제공한다. According to another embodiment, a cosmetic composition for preventing or improving atopic dermatitis containing roliolide is provided.
상기 목적을 달성하기 위하여, 본 발명의 일 양상은 롤리올라이드를 유효성분으로 포함하는 아토피 피부염의 예방 또는 치료용 약학적 조성물을 제공한다. In order to achieve the above object, one aspect of the present invention provides a pharmaceutical composition for preventing or treating atopic dermatitis comprising roliolide as an active ingredient.
본 명세서에서 사용된 용어, “예방”은 본 발명에 따른 약학 조성물의 투여에 의해 아토피 피부염을 억제시키거나 발병을 지연시키는 모든 행위를 의미한다.As used herein, the term "prevention" refers to any action that suppresses or delays the onset of atopic dermatitis by administration of the pharmaceutical composition according to the present invention.
본 명세서에서 사용된 용어, “치료”는 본 발명에 따른 약학 조성물의 투여에 의해 아토피 피부염에 대한 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.As used herein, the term "treatment" refers to all activities that improve or beneficially change the symptoms of atopic dermatitis by administration of the pharmaceutical composition according to the present invention.
상기 조성물에 의한 예방 또는 치료 대상 질병인 “아토피 피부염(atopic dermatitis)”은 유전적, 환경적, 면역학적인 원인에 의해 발생하고, 피부 가장 바깥에서 보호벽 역할을 하는 각질층에 이상이 생긴 것으로 건조한 기후에서 더욱 심해지는 알레르기 질환 중 하나이다. 아토피 피부염의 주요 증상은 심한 가려움증, 피부건조, 발진, 진물, 부스럼딱지, 비늘 같은 껍질이 있는 피부(인비늘) 등으로 주로 만성 피부염증이 동반된다. 이러한 아토피 피부염의 원인은 잘 알려져 있지 않으나 주로 유전적인 요소가 많고 면역 반응과 관련되어 있는 것으로 밝혀져 있으며, 그 외에 건조한 피부, 정상인에 비해 쉽게 피부 가려움증을 느끼는 특성, 세균, 바이러스 및 곰팡이 등에 의한 감염, 정서적 요인 및 환경적 요인 등이 서로 복합적으로 작용하여 일어나는 것으로 보인다. "Atopic dermatitis", a disease to be prevented or treated by the composition, is caused by genetic, environmental, and immunological causes, and is caused by an abnormality in the stratum corneum, which serves as a protective barrier on the outermost layer of the skin, and is treated in a dry climate. It is one of the more severe allergic diseases. The main symptoms of atopic dermatitis are severe itching, skin dryness, rash, ooze, scab, and scaly skin (scaly skin), which are mainly accompanied by chronic skin inflammation. The cause of atopic dermatitis is not well known, but it has been found that there are many genetic factors and it is related to the immune response. Emotional factors and environmental factors seem to be caused by a complex interaction with each other.
본 발명의 일 구체예에 따르면, 상기 “롤리올라이드”는 하기 화학식 1로 표시되는 화합물일 수 있다.According to one embodiment of the present invention, the “roliolide” may be a compound represented by Formula 1 below.
[화학식 1][Formula 1]
일 구체예에 따르면 상기 조성물은 괭생이모자반 추출물로부터 분리된 것일 수 있다. According to one embodiment, the composition may be separated from the extract of thoracotalis capitis.
상기 괭생이모자반 (Sargassum horneri)은 모자반목 모자반과에 속하는 갈조류로 한국 남해안 및 일본의 전 연안에서 서식하고 있으며 주로 사료로 사용되고 있다. Sargassum horneri is a brown algae belonging to the family Sargassum horneri, which lives in the southern coast of Korea and all the coasts of Japan, and is mainly used as feed.
일 구체예에 따르면, 상기 괭생이모자반 추출물은 당업계에 공지된 통상의 방법에 따라, 예컨대, 통상적인 온도와 압력의 조건 하에서, 통상적인 용매를 이용한 용매 추출법을 이용하여 얻을 수 있다. 상기 추출공정은 패 무게에 대하여 약 2 내지 20 배, 바람직하게는 약 5 내지 10 배의 상기 1차 추출용매로 추출함으로써 수행할 수 있다. 추출은 당 분야에 알려진 추출방법, 예컨대, 냉침, 열수추출, 초음파 추출, 환류 냉각 추출 등의 방법으로 수행될 수 있으나, 이에 국한되지 않는다. 추출온도는 당업자가 추출 방법에 적절한 다양한 온도 범위를 채택할 수 있으며, 예를 들어, 20 ℃ 내지 100 ℃ 등에서 수행될 수 있으나, 이에 국한되지 않는다. 또한, 추출시간은 추출방법에 따라 상이하며, 당업자가 적절한 추출시간을 채택할 수 있으며, 이에 국한되지 않으나, 약 1 시간 내지 수일의 범위에서 단회 또는 복수회로 수행될 수 있다. 상기 1차 추출용매로 추출을 수행하여 얻어진 추출물은 통상의 방법에 따라 여과하여 불순물을 제거한 액상 형태로 얻거나, 얻어진 액상 형태의 추출물을 통상의 방법에 따라 감압농축 및/또는 건조하여 분말 형태로 얻을 수 있다.According to one embodiment, the extract of the thorax capsicum can be obtained according to a conventional method known in the art, for example, by using a solvent extraction method using a conventional solvent under normal conditions of temperature and pressure. The extraction step may be performed by extracting with the primary extraction solvent about 2 to 20 times, preferably about 5 to 10 times the shell weight. Extraction may be performed by extraction methods known in the art, such as cold brewing, hot water extraction, ultrasonic extraction, reflux cooling extraction, and the like, but is not limited thereto. The extraction temperature may be selected by those skilled in the art in various temperature ranges suitable for the extraction method, and may be performed at, for example, 20 °C to 100 °C, but is not limited thereto. In addition, the extraction time differs depending on the extraction method, and a person skilled in the art may select an appropriate extraction time, but is not limited thereto, and may be performed single or multiple times in the range of about 1 hour to several days. The extract obtained by performing the extraction with the primary extraction solvent is obtained in liquid form from which impurities are removed by filtering according to a conventional method, or the obtained liquid extract is concentrated under reduced pressure and / or dried according to a conventional method to obtain a powder form. You can get it.
본 발명에서 바람직한 추출 용매로는 에탄올, 바람직하게는 30% 내지 100% 에탄올을 이용할 수 있다. 더욱 바람직하게는 70% 에탄올을 이용할 수 있다.Ethanol, preferably 30% to 100% ethanol may be used as a preferred extraction solvent in the present invention. More preferably, 70% ethanol can be used.
본 명세서에서 "유효성분"이란 단독으로 목적하는 활성을 나타내거나 또는 그 자체는 활성이 없는 담체와 함께 활성을 나타낼 수 있는 성분을 의미한다.In the present specification, "active ingredient" means a component that exhibits the desired activity alone or can exhibit activity in combination with a carrier having no activity itself.
상기 약학적 조성물은 투여를 위해서 상기 기재한 롤리올라이드 이외에 추가로 약학적으로 허용 가능한 담체를 1종 이상 포함하여 약학적 조성물로 바람직하게 제제화할 수 있다.For administration, the pharmaceutical composition may be preferably formulated as a pharmaceutical composition by including at least one pharmaceutically acceptable carrier in addition to the above-described rolyolide.
상기 약학적 조성물의 제제 형태는 과립제, 산제, 정제, 피복정, 캡슐제, 좌제, 액제, 시럽, 즙, 현탁제, 유제, 점적제 또는 주사 가능한 액제 등이 될 수 있다. 예를 들어, 정제 또는 캡슐제의 형태로의 제제화를 위해, 유효 성분은 에탄올, 글리세롤, 물 등과 같은 경구, 무독성의 약학적으로 허용 가능한 불활성 담체와 결합될 수 있다. 또한, 원하거나 필요한 경우, 적합한 결합제, 윤활제, 붕해제 및 발색제 또한 혼합물로 포함될 수 있다. 적합한 결합제는 이에 제한되는 것은 아니나, 녹말, 젤라틴, 글루코스 또는 베타-락토오스와 같은 천연 당, 옥수수 감미제, 아카시아, 트래커캔스 또는 소듐올레이트와 같은 천연 및 합성 검, 소듐 스테아레이트, 마그네슘 스테아레이트, 소듐 벤조에이트, 소듐 아세테이트, 소듐 클로라이드 등을 포함한다. 붕해제는 이에 제한되는 것은 아니나, 녹말, 메틸 셀룰로스, 아가, 벤토니트, 잔탄 검 등을 포함한다. Formulations of the pharmaceutical composition may be granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops, or injectable solutions. For example, for formulation in the form of tablets or capsules, the active ingredient may be combined with an oral, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. In addition, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included in the mixture. Suitable binders include, but are not limited to, starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tracacanth or sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.
액상 용액으로 제제화되는 조성물에 있어서 허용 가능한 약학적 담체로는, 멸균 및 생체에 적합한 것으로서, 식염수, 멸균수, 링거액, 완충 식염수, 알부민 주사용액, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한, 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다.In compositions formulated as liquid solutions, acceptable pharmaceutical carriers are sterile and biocompatible, and include saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostatic agents may be added if necessary. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to prepare formulations for injections such as aqueous solutions, suspensions, and emulsions, pills, capsules, granules, or tablets.
본 발명의 약학적 조성물은 경구 또는 비경구로 투여할 수 있고, 비경구 투여인 경우에는 정맥 내 주입, 피하 주입, 근육 주입, 복강 주입, 경피 투여 등으로 투여할 수 있다.The pharmaceutical composition of the present invention can be administered orally or parenterally, and in the case of parenteral administration, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc. can be administered.
본 발명의 약학적 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 결정될 수 있다. A suitable dosage of the pharmaceutical composition of the present invention may be determined by factors such as formulation method, administration method, patient's age, weight, sex, morbid condition, food, administration time, administration route, excretion rate and reaction sensitivity. .
본 발명의 약학적 조성물은 당해 발명이 속하는 기술 분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있는 방법에 따라, 약학적으로 허용되는 담체 및/또는 부형제를 이용하여 제제화 함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다.The pharmaceutical composition of the present invention is prepared in unit dosage form by formulation using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily performed by those skilled in the art. or it may be prepared by incorporating into a multi-dose container.
본 발명의 다른 양상은 롤리올라이드를 포함하는 아토피 피부염의 예방 또는 개선용 식품 조성물을 제공한다.Another aspect of the present invention provides a food composition for preventing or improving atopic dermatitis containing roliolide.
본 발명에서 사용되는 용어, “개선”이란, 치료되는 상태와 관련된 파라미터, 예를 들면 증상의 정도를 적어도 감소시키는 모든 행위를 의미한다. 이때 상기 건강기능성 식품 조성물은 아토피피부염의 예방 또는 개선을 위하여 해당 질환의 발병 단계 이전 또는 발병 후, 치료를 위한 약제와 동시에 또는 별개로서 사용될 수 있다.As used herein, the term "improvement" refers to all actions that at least reduce the parameters related to the condition to be treated, for example, the severity of symptoms. In this case, the health functional food composition may be used simultaneously with or separately from a drug for treatment before or after the onset of the disease in order to prevent or improve atopic dermatitis.
본 발명에 따른 식품 조성물은 상기 약학적 조성물과 동일한 방식으로 제제화하여 기능성 식품으로 이용하거나, 각종 식품에 첨가할 수 있다. 본 발명의 조성물을 첨가할 수 있는 식품으로는 예를 들어, 음료류, 과자류, 다이어트바, 유제품, 육류, 초코렛, 피자, 라면, 기타 면류, 껌류, 아이스크림류, 비타민 복합제, 건강보조식품류 등이 있다.The food composition according to the present invention can be formulated in the same way as the pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, confectionery, diet bars, dairy products, meat, chocolate, pizza, ramen, other noodles, chewing gum, ice cream, vitamin complexes, and health supplements. .
본 발명의 식품 조성물은 롤리올라이드를 포함하는 이외에 식품 제조 시에 통상적으로 첨가되는 성분을 포함할 수 있으며, 예를 들어, 단백질, 탄수화물, 지방, 영양소, 조미제 및 향미제를 포함한다. 상술한 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스, 올리고당 등; 및 폴리사카라이드, 예를 들어 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 향미제로서 천연 향미제 [타우마틴, 스테비아 추출물 (예를 들어 레바우디오시드 A, 글리시르히진 등)] 및 합성 향미제(사카린, 아스파르탐 등)를 사용할 수 있다. 예를 들어, 본 발명의 식품 조성물이 드링크제와 음료류로 제조되는 경우에는 본 발명의 롤리올라이드 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 및 각종 식물 추출액 등을 추가로 포함시킬 수 있다. The food composition of the present invention may include ingredients commonly added during food preparation in addition to containing rolyolide, and include, for example, proteins, carbohydrates, fats, nutrients, seasonings and flavors. Examples of the aforementioned carbohydrates include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sucrose, oligosaccharides and the like; and polysaccharides such as conventional sugars such as dextrins and cyclodextrins and sugar alcohols such as xylitol, sorbitol and erythritol. As flavoring agents, natural flavoring agents [thaumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.)] and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is prepared as a drink or beverage, citric acid, high fructose corn syrup, sugar, glucose, acetic acid, malic acid, fruit juice, and various plant extracts may be further included in addition to the rolliolide of the present invention. can
본 발명의 다른 양상은 롤리올라이드를 포함하는 아토피 피부염의 예방 또는 개선용 화장품 조성물을 제공한다.Another aspect of the present invention provides a cosmetic composition for preventing or improving atopic dermatitis, which includes roliolide.
본 발명의 화장품 조성물을 첨가할 수 있는 제품으로는, 예를 들어, 각종 스킨로션, 스킨소프너, 스킨토너, 아스트린젠트, 로션, 밀크로션, 영양로션, 마사지크림, 영양크림, 핸드크림, 파운데이션, 메이크업베이스, 트윈케익, 마스카라, 에센스, 영양에센스, 팩, 비누, 클렌징폼, 클렌징로션, 클렌징크림, 바디로션 또는 바디클렌저일 수 있다. Products to which the cosmetic composition of the present invention can be added include, for example, various skin lotions, skin softeners, skin toners, astringents, lotions, milk lotions, nutrient lotions, massage creams, nutrient creams, hand creams, foundations, and makeup. It may be a base, twin cake, mascara, essence, nutritional essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion, or body cleanser.
본 발명의 화장품 조성물이 상술한 형태의 제형으로 제조될 때, 그 제형의 제제화에 필요하고 적절한 각종의 기제와 첨가물을 함유할 수 있다. 또한, 이들 성분의 종류와 양은 당업자에 의해 용이하게 선정될 수 있다.When the cosmetic composition of the present invention is prepared in the above-described formulation, it may contain various bases and additives necessary and suitable for formulating the formulation. In addition, the types and amounts of these components can be easily selected by those skilled in the art.
예를 들어, 본 발명의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물성유, 식물성유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있다.For example, when the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide as a carrier component etc. can be used.
또 다른 예로, 본 발명의 제형이 용액 또는 유탁액인 경우에는 담체 성분으로서 용매, 용해화제 또는 유탁화제가 이용되고, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 사용될 수 있다.As another example, when the formulation of the present invention is a solution or emulsion, a solvent, solubilizing agent or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, Propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic esters, polyethylene glycol or fatty acid esters of sorbitan may be used.
또 다른 예로, 본 발명의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상의 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소 결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 이용될 수 있다.As another example, when the formulation of the present invention is a suspension, a liquid diluent such as water, ethanol or propylene glycol, an ethoxylated isostearyl alcohol, a suspension such as polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester as a carrier component agent, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tracanth, and the like may be used.
또 다른 예로, 본 발명의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로 플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다.As another example, when the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and in particular, in the case of a spray, chlorofluoro propellants such as hydrocarbons, propane/butane or dimethyl ether.
또 다른 예로, 본 발명의 제형이 계면활성제 함유 클렌징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성 유, 라놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.As another example, when the formulation of the present invention is surfactant-containing cleansing, as carrier components, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, and sarcosinate , fatty acid amide ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, or ethoxylated glycerol fatty acid esters.
또한, 본 발명의 화장품 조성물은 단독 또는 중복하여 사용하거나, 본 발명 이외의 다른 화장품 조성물과 중복하여 사용할 수 있다. 또한 본 발명에 따른 화장품 조성물은 통상적인 사용방법에 따라 사용될 수 있으며, 사용자의 피부 상태 또는 취향에 따라 그 사용횟수를 달리할 수 있다.In addition, the cosmetic composition of the present invention can be used alone or overlapping, or overlapping with other cosmetic compositions other than the present invention. In addition, the cosmetic composition according to the present invention can be used according to a conventional method of use, and the number of times of use can be varied according to the user's skin condition or taste.
일 구체예에 따른 롤리올라이드를 유효성분으로 포함하는 약학적 조성물은 수분 손실, 가려움증, 부종 등의 아토피 피부염의 임상증상을 개선하여 아토피 피부염의 예방 또는 치료 용도로 유용하게 사용될 수 있다. A pharmaceutical composition containing roliolide according to one embodiment as an active ingredient can be usefully used for preventing or treating atopic dermatitis by improving clinical symptoms of atopic dermatitis, such as water loss, itching, and edema.
도 1은 DNCB로 아토피 피부염을 유도한 마우스에 롤리올라이드 또는 CJLP133을 경구 투여한 후 아토피 피부염의 임상 증상을 점수화한 결과를 나타낸 것이다.
도 2는 DNCB로 아토피 피부염을 유도한 마우스에 롤리올라이드 또는 CJLP133을 경구 투여한 후 경피 수분 손실 정도를 측정한 결과를 나타낸 것이다.
도 3은 DNCB로 아토피 피부염을 유도한 마우스에 롤리올라이드 또는 CJLP133을 경구 투여한 후 피부 가려움 정도를 긁는 횟수로 측정한 결과를 나타낸 것이다.
도 4는 DNCB로 아토피 피부염을 유도한 마우스에 롤리올라이드 또는 CJLP133을 경구 투여한 후 마우스의 양쪽 귀의 두께를 측정한 결과를 나타낸 것이다.Figure 1 shows the results of scoring clinical symptoms of atopic dermatitis after oral administration of loliolide or CJLP133 to mice induced atopic dermatitis with DNCB.
Figure 2 shows the results of measuring the degree of transepidermal water loss after oral administration of loliolide or CJLP133 to mice induced atopic dermatitis with DNCB.
Figure 3 shows the results of measuring the degree of skin itching by the number of scratches after oral administration of loliolide or CJLP133 to mice induced atopic dermatitis with DNCB.
Figure 4 shows the results of measuring the thickness of both ears of mice after oral administration of loliolide or CJLP133 to mice induced atopic dermatitis with DNCB.
이하 하나 이상의 구체예를 실시예를 통해 보다 상세하게 설명한다. 그러나, 이들 실시예는 하나 이상의 구체예를 예시적으로 설명하기 위한 것으로 본 발명의 범위가 이들 실시예에 한정되는 것은 아니다.Hereinafter, one or more specific examples will be described in more detail through examples. However, these examples are intended to illustrate one or more specific examples, and the scope of the present invention is not limited to these examples.
실시예 1: 재료준비 - 롤리올라이드 준비Example 1: Material Preparation - Roliolide Preparation
1-1.1-1. 괭생이모자반 추출물 제조Manufacture of hoesaeng hatban extract
본 실험에 사용된 괭생이모자반(Sargassum horneri)은 물로 3회 세척하여 염과 모래를 제거하였다. 그리고 -70℃에서 2시간 동안 냉동시킨 뒤 3일간 동결건조하였다. 건조한 각 모자반은 사용 전까지 냉장실에 보관하였다. 실험에 사용된 DMEM은 Hyclone사 제품을 사용하였으며, fetal bovine serum(FBS)과 페니실린, NE-PER nuclear and cytoplasmic extraction kit는 Thermo Fisher Scientific 제품을 사용하였다. 그 외 모든 분석시약은 특급 또는 HPLC급 시약을 사용하였다. The hoesaeng cap ( Sargassum horneri ) used in this experiment was washed three times with water to remove salt and sand. And after freezing at -70 ℃ for 2 hours, it was lyophilized for 3 days. Each dried hat half was stored in a refrigerator until use. DMEM used in the experiment was a product of Hyclone, and fetal bovine serum (FBS), penicillin, and NE-PER nuclear and cytoplasmic extraction kit were a product of Thermo Fisher Scientific. For all other analytical reagents, special grade or HPLC grade reagents were used.
괭생이모자반 파우더를 70% 에탄올과 1:50 비율로 70℃에서 24시간 추출하고 원심분리(4000rpm, 20min)한 뒤, 여과지(Whatman No.6)로 여과하였다. 제조된 70% 에탄올 추출물을 감압농축 및 동결건조하여 실험에 사용하였다. The hoesaeng hatban powder was extracted with 70% ethanol at a ratio of 1:50 at 70 ° C for 24 hours, centrifuged (4000 rpm, 20 min), and filtered with filter paper (Whatman No. 6). The prepared 70% ethanol extract was concentrated under reduced pressure and lyophilized and used in the experiment.
1-2.1-2. 롤리올라이드 분리Isolation of loliolide
괭생이모자반 에탄올 추출물로부터 유용성분인 롤리올라이드를 분리 및 정제하여 실험에 사용하였다. 롤리올라이드의 구조식은 하기 화학식 1과 같다.Roliolide, a useful ingredient, was isolated and purified from the ethanol extract of the oyster cap and was used in the experiment. The structural formula of roliolide is the following
[화학식 1] [Formula 1]
실시예 2: 아토피 피부염의 증상 개선 효과 평가 방법Example 2: Method for evaluating the symptom improvement effect of atopic dermatitis
2-1. 실험 동물 및 실험 방법2-1. Experimental animals and experimental methods
롤리올라이드의 아토피 피부염 증상 개선 효과를 실험적으로 확인하기 위해 당업계에 공지된 동물모델인 Balb/C마우스를 사용하였다.Balb/C mice, an animal model known in the art, were used to experimentally confirm the effect of improving atopic dermatitis symptoms of Roliolide.
아토피 피부염 동물모델에서 롤리올라이드의 아토피 피부염 개선 및 면역조절 효능을 평가하기 위해, 마우스를 무처리군(naive)과 아토피 피부염 유발군으로 나누고, 아토피 피부염 유발군은 다시 DNCB(dinitrochlorobenzene) 처리군(음성 대조군), DNCB 및 롤리올라이드(10 mg/kg) 처리군(롤리올라이드), 그리고 DNCB 및 CJLP133(CJ Cheiljedang Co. Seoul, Korea, 800 mg/kg) 처리군(양성 대조군)으로 나누었다.In order to evaluate the atopic dermatitis improvement and immunomodulatory efficacy of rolliolide in an atopic dermatitis animal model, mice were divided into a naive group and an atopic dermatitis-induced group, and the atopic dermatitis-induced group was treated with DNCB (dinitrochlorobenzene) ( negative control group), DNCB and loliolide (10 mg/kg) treatment group (roliolide), and DNCB and CJLP133 (CJ Cheiljedang Co. Seoul, Korea, 800 mg/kg) treatment group (positive control group).
즉, 등 부위를 제모한 Balb/C 마우스에 1% DNCB 를 도포하여 1차적으로 아토피성 피부염증을 유도하고, 일주일 뒤 0.5% DNCB를 제모한 부위에 도포하여 2차적으로 유도하였다. 이 후 3주간 0.5% DNCB를 2일에 한번씩 도포하여 3차적으로 아토피성 피부염을 유도하여 지속시키는 동시에, 매일 롤리올라이드 (10 mg/kg) 및 양성 대조군에 CJLP133을 3주 동안 경구투여 하였다. That is, atopic dermatitis was induced primarily by applying 1% DNCB to Balb/C mice depilated on the back, and secondarily induced by applying 0.5% DNCB to the depilated area one week later. Thereafter, 0.5% DNCB was applied once every 2 days for 3 weeks to induce and sustain atopic dermatitis in a third way, and at the same time, loliolide (10 mg/kg) and CJLP133 were orally administered to the positive control group for 3 weeks.
마우스의 체중, 임상 분석, 가려움 (scratching), 경피 수분 손실 (transepidermal water loss, TEWL)은 매주 측정하였으며, 실험 종료 후 동물을 희생시켜 귀 두께를 측정하였다.The body weight, clinical analysis, scratching, and transepidermal water loss (TEWL) of the mice were measured weekly, and after the experiment, the animals were sacrificed and the ear thickness was measured.
2-2. 롤리올라이드의 임상증상 변화에 미치는 영향 평가2-2. Evaluation of the effect of roliolide on changes in clinical symptoms
아토피성 피부염 동물모델에서 롤리올라이드의 아토피 개선 및 면역조절 효능을 평가하기 위하여 동물 실험기간 동안 매주 피부 임상 증상 변화를 가려움증, 홍반 및 출혈, 부종, 귀 부위의 상처 및 건조로 나누어 하기의 표 1과 같이 점수화하여 평가하였다.In order to evaluate the atopic improvement and immunomodulatory efficacy of lolliolide in atopic dermatitis animal models, weekly changes in skin clinical symptoms during the animal experiment were divided into itching, erythema and bleeding, edema, wounds and dryness in the ear area, Table 1 below It was evaluated by scoring as follows.
2-3. 롤리올라이드의 피부 수분 손실 억제 효과 평가2-3. Evaluation of skin moisture loss inhibitory effect of lolliolide
아토피성 피부염의 대표적 임상증상인 피부 건조도를 평가하기 위하여 주 1회 각 마우스의 경피 수분 손실도를 측정하였다. 동물을 마취시킨 후, 아토피가 유도된 마우스의 등 부위에 경피 수분 손실 측정 장비(AquaFlux, Biox)를 이용하여 30초 동안 측정하였다.In order to evaluate skin dryness, which is a representative clinical symptom of atopic dermatitis, transdermal water loss of each mouse was measured once a week. After the animal was anesthetized, the back of the atopy-induced mouse was measured for 30 seconds using a transdermal water loss measuring device (AquaFlux, Biox).
2-4. 롤리올라이드의 피부 가려움증 증상 개선 효과 평가2-4. Evaluation of skin itching symptom improvement effect of lolliolide
아토피 피부염의 대표적인 임상증상인 피부 가려움 증상 변화를 평가하였다. 아토피를 유도하기 전과 후, 양성 대조군에는 CJLP133을, 실험군에는 롤리올라이드를 투여한 후의 가려움 증상을 비교 관찰하기 위해 매주 암 조건에서 10분 동안 마우스의 행동을 촬영하고, 이를 관찰하여 긁는 횟수를 측정하였다.Changes in skin itching, a typical clinical symptom of atopic dermatitis, were evaluated. Before and after inducing atopy, in order to compare and observe the itching symptoms after administering CJLP133 to the positive control group and loliolide to the experimental group, the behavior of the mouse was photographed for 10 minutes in the dark condition every week, and the number of scratches was measured by observing it. did
2-5. 롤리올라이드의 부종 개선 효과 평가2-5. Evaluation of the edema improvement effect of lolliolide
아토피 피부염에 의해 유발된 귀 부종에 대한 롤리올라이드의 영향을 확인하기 위해 6주차에 각 그룹의 귀 두께를 측정하였다. 동물을 마취시킨 후, caliper (Hornady, GI, USA)를 이용하여 마우스 오른쪽 귀와 왼쪽 귀를 각각 세 부분으로 나누어 두께를 측정하였으며, 이들의 평균값으로 귀 부종 정도를 나타내었다.Ear thickness of each group was measured at 6 weeks to confirm the effect of loliolide on ear edema induced by atopic dermatitis. After the animal was anesthetized, the right and left ears of the mouse were divided into three parts using a caliper (Hornady, GI, USA), and the thickness was measured.
2-6. 통계 처리 2-6. statistical processing
상기 실험 결과는 PASW Statistics 19.0 software (SPSS, Chicago, IL, USA)를 사용하여 통계적 유의성에 대해 평가하였으며, 각 실험군 간의 평균치의 유의성을 p<0.01 수준에서 Duncan's test를 사용하여 비교하였다.The experimental results were evaluated for statistical significance using PASW Statistics 19.0 software (SPSS, Chicago, IL, USA), and the significance of the average value between each experimental group was compared using Duncan's test at the p<0.01 level.
3. 아토피 피부염의 증상 개선 효과 평가 결과3. Results of evaluation of symptom improvement effect of atopic dermatitis
3-1. 롤리올라이드의 임상 증상 변화에 미치는 영향 평가 3-1. Evaluation of the effect of roliolide on changes in clinical symptoms
1% DNCB를 처리한 1주차에는 무처리군을 제외한 나머지 군에서 평균 1.7 ± 0.2점의 다소 약한 임상증상 점수를 보였으나, 0.5% DNCB를 도포하여 2차적으로 아토피 피부염을 유도한 3주차에서는 무처리군을 제외한 모든 동물 군에서 평균 6.05 ± 0.17점으로 마우스 피부에 각질과 상처 등 아토피 피부염이 유발된 것을 확인할 수 있었다 (도 1). 롤리올라이드와 CJLP133을 투여하기 시작한 3주차에서는 DNCB만 처리한 음성 대조군이 8.03 ± 0.18점으로 3주차보다 높은 점수를 보였으며, 롤리올라이드와 CJLP133을 투여한 군에서는 각각 5.70 ± 0.16점 및 5.28 ± 0.17점으로 음성 대조군보다 감소된 것을 확인할 수 있었다. 특히, 실험 6주차에서는 롤리올라이드를 처리한 마우스 군에서 1.80 ± 0.13점으로 아토피 피부염의 증상이 현저하게 완화된 것을 확인할 수 있었다.In the first week of treatment with 1% DNCB, the remaining groups except for the untreated group showed an average of 1.7 ± 0.2 points for slightly weaker clinical symptoms, but in the third week when atopic dermatitis was secondarily induced by applying 0.5% DNCB, there was no In all animal groups except the treatment group, it was confirmed that atopic dermatitis, such as keratin and wounds, was induced in the mouse skin with an average score of 6.05 ± 0.17 (FIG. 1). At the 3rd week of administration of lolliolide and CJLP133, the negative control group treated with only DNCB scored 8.03 ± 0.18 points, which was higher than that of the 3rd week. It was confirmed that it was reduced than the negative control by ± 0.17 points. In particular, in the 6th week of the experiment, it was confirmed that the symptoms of atopic dermatitis were remarkably alleviated with a score of 1.80 ± 0.13 in the mouse group treated with loliolide.
3-2. 롤리올라이드가 피부 수분 손실에 미치는 영향 평가3-2. Evaluation of the effect of roliolide on skin water loss
1% DNCB를 처리한 1 주차에는 모든 그룹의 경피 수분 손실도가 15.72 ± 0.34 g/m2/hr으로 아무것도 처리하지 않은 0주차(6.62 ± 0.41 g/m2/hr) 보다 다소 증가되었으며, 0.5% DNCB를 도포하여 2차적으로 아토피 피부염을 유도한 2주차에서는 무처리군을 제외한 나머지 그룹에서 평균 61.30 ± 0.46 g/m2/hr으로 피부로부터 수분손실이 증가된 것을 확인할 수 있었다. 이는 DNCB처리에 의해 피부장벽이 손상되었다는 것을 의미한다. 그러나, 4주차에서는 롤리올라이드를 투여한 마우스 그룹의 경우 각각 59.0 ± 1.6 g/m2/hr로 수분 손실 정도가 감소된 것을 확인할 수 있었으며, 특히, 6주차에서는 롤리올라이드를 투여한 마우스 그룹이 23.8 ± 1.1 g/m2/hr로 DNCB만 처리한 군보다 유의적으로 피부 수분 손실정도가 억제된 것을 확인할 수 있었다 (도 2). 이러한 결과는, 롤리올라이드가 DNCB에 의해 손상된 피부장벽기능을 강화했음을 제시한다.At
3-3. 롤리올라이드가 피부 가려움 증상에 미치는 영향 평가3-3. Evaluation of the effect of roliolide on skin itching symptoms
1% DNCB를 처리한 1주차에는 모든 그룹이 평균 7.4 ± 1.3번으로 아무것도 처리하지 않은 0주차 (평균 0.00 ± 0.00번)보다 다소 긁는 횟수가 증가한 것을 확인할 수 있었으며, 0.5% DNCB를 도포하여 2차적으로 아토피 피부염을 유도한 2주차에서는 무처리군을 제외한 나머지 그룹에서 평균 12.1 ± 1.11번으로 긁는 횟수가 유의적으로 증가된 것을 확인할 수 있었다. 이는 피부장벽손상에 의한 건조에 의해 발생된 것으로, DNCB를 처리 시 피부장벽손상과 더불어 수분함량 저하에도 영향을 주는 것으로 확인하였다. 그러나, 롤리올라이드 투여를 시작한 4주차에서는 10.2 ± 0.8번으로, DNCB만 처리한 군의 15.9 ± 1.2번보다 긁는 횟수가 감소된 것을 확인할 수 있었으며, 특히, 6주차에서는 롤리올라이드 투여군은 4.5 ± 0.2번으로 유의적으로 DNCB만 처리한 그룹보다 긁는 횟수가 감소된 것을 확인할 수 있었다 (도 3). 이러한 결과는, 롤리올라이드가 DNCB에 의해 손상된 피부장벽기능을 강화함으로써 피부건조를 개선했음을 제시한다.In the first week of treatment with 1% DNCB, all groups showed an average of 7.4 ± 1.3 scratches, slightly increasing the number of scratches compared to week 0 (average of 0.00 ± 0.00 times) when nothing was treated. In the 2nd week after atopic dermatitis was induced, it was confirmed that the number of scratches significantly increased with an average of 12.1 ± 1.11 times in the remaining groups except for the untreated group. This was caused by drying due to damage to the skin barrier, and it was confirmed that the treatment of DNCB affected the decrease in moisture content as well as damage to the skin barrier. However, it was confirmed that the number of scratches was reduced to 10.2 ± 0.8 at the 4th week after administration of rolliolide, compared to 15.9 ± 1.2 times in the DNCB-only treated group. It was confirmed that the number of scratches was significantly reduced by 0.2 times compared to the group treated only with DNCB (FIG. 3). These results suggest that roliolide improved skin dryness by enhancing the skin barrier function damaged by DNCB.
3-4. 롤리올라이드가 귀 부종에 미치는 영향 평가3-4. Evaluation of the effect of lolliolide on ear edema
무처리군의 귀 두께는 0.14 ± 0.01 mm로 측정되었으나, DNCB만 처리한 마우스 군의 귀 두께는 0.66 ± 0.03 mm로 나타나 아토피성 피부염에 의해 귀 부종이 유도된 것을 확인할 수 있었다. 반면, 롤리올라이드를 처리한 마우스의 귀 두께의 경우 각각 0.23 ± 0.02 mm로 나타나 아토피성 피부염 군과 비교하였을 때, 유의적으로 귀 부종이 감소된 것을 확인할 수 있었다 (도 4).The ear thickness of the non-treated group was measured as 0.14 ± 0.01 mm, but the ear thickness of the mouse group treated only with DNCB was 0.66 ± 0.03 mm, indicating that ear edema was induced by atopic dermatitis. On the other hand, in the case of the ear thickness of the mice treated with roliolide, each was 0.23 ± 0.02 mm, and it was confirmed that ear swelling was significantly reduced when compared to the atopic dermatitis group (FIG. 4).
이제까지 본 발명에 대하여 그 바람직한 실시예들을 중심으로 살펴보았다. 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자는 본 발명이 본 발명의 본질적인 특성에서 벗어나지 않는 범위에서 변형된 형태로 구현될 수 있음을 이해할 수 있을 것이다. 그러므로 개시된 실시예들은 한정적인 관점이 아니라 설명적인 관점에서 고려되어야 한다. 본 발명의 범위는 전술한 설명이 아니라 특허청구범위에 나타나 있으며, 그와 동등한 범위 내에 있는 모든 차이점은 본 발명에 포함된 것으로 해석되어야 할 것이다.So far, the present invention has been looked at with respect to its preferred embodiments. Those skilled in the art to which the present invention pertains will be able to understand that the present invention can be implemented in a modified form without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments should be considered from an illustrative rather than a limiting point of view. The scope of the present invention is shown in the claims rather than the foregoing description, and all differences within the equivalent scope will be construed as being included in the present invention.
Claims (5)
아토피 피부염 예방 또는 치료용 약학적 조성물
[화학식 1]
Containing as an active ingredient a loliolide represented by Formula 1 below,
Pharmaceutical composition for preventing or treating atopic dermatitis
[Formula 1]
상기 조성물은 괭생이모자반 추출물로부터 분리된 것인,
아토피 피부염 예방 또는 치료용 약학적 조성물.
The method of claim 1,
The composition is isolated from the extract of the black thrips,
A pharmaceutical composition for preventing or treating atopic dermatitis.
상기 괭생이모자반 추출물은 70% 에탄올 추출물인 것인,
아토피 피부염 예방 또는 치료용 약학적 조성물.
The method of claim 1,
The hoesaeng hatban extract is a 70% ethanol extract,
A pharmaceutical composition for preventing or treating atopic dermatitis.
[화학식 1]
A food composition for preventing or improving atopic dermatitis comprising a roliolide represented by Formula 1 below.
[Formula 1]
[화학식 1]
A cosmetic composition for preventing or improving atopic dermatitis, comprising a roliolide represented by Formula 1 below.
[Formula 1]
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