KR101440780B1 - Composition for Improving Allergy Disease Using the Effective Compound Which Cay Be Isolated from an Extract of Wheat Bran - Google Patents
Composition for Improving Allergy Disease Using the Effective Compound Which Cay Be Isolated from an Extract of Wheat Bran Download PDFInfo
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- KR101440780B1 KR101440780B1 KR1020100138902A KR20100138902A KR101440780B1 KR 101440780 B1 KR101440780 B1 KR 101440780B1 KR 1020100138902 A KR1020100138902 A KR 1020100138902A KR 20100138902 A KR20100138902 A KR 20100138902A KR 101440780 B1 KR101440780 B1 KR 101440780B1
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Abstract
본 발명은 밀겨 추출물로부터 분리될 수 있는 유효물질인 5-n-노나데실레조시놀(5-n-nonadecylresorcinol) 또는 5-n-헤네코실레조시놀을 이용한 알러지성 질환의 개선제 조성물을 개시한다. 상기 유효물질은 탈과립 억제 활성, 사이토카인의 생성 억제 활성, p-AKT의 생성 억제 활성 등을 가지고 있다. The present invention discloses an ameliorative agent composition for allergic diseases using 5-n-nonadecylresorcinol or 5-n-henecyl silezocinol, which is an effective substance that can be separated from a pressed extract . The active substance has a degranulation inhibitory activity, a cytokine inhibitory activity, and a p-AKT inhibitory activity.
Description
본 발명은 밀겨(Wheat Bran) 추출물로부터 분리될 수 있는 유효물질을 이용한 알러지성 질환의 개선제 조성물에 관한 것이다.
The present invention relates to an agent composition for the amelioration of an allergic disease using an effective substance which can be isolated from Wheat Bran extract.
알러지(allergy)란 일반적으로 이물질인 알러지원(allergen)에 의해 면역학적 기전을 통해 야기되는 반응으로 신체에 해로운 손상을 유발하는 현상을 말한다.Allergies are allergens that cause harmful damage to the body, usually caused by an allergen, a reaction caused by an immunological mechanism.
비만세포(mast cell)는 알러지 반응을 매개하는 중요한 세포로, 피부, 호흡기, 위장관의 점막, 임파관 주위, 혈관 주위, 뇌 등 전신의 장기에 널리 분포하여 있으며, 세포질 내 풍부한 과립을 가지고 있다.Mast cells are important cells mediating the allergic reaction. They are widely distributed in the organs of the skin, the respiratory tract, the mucous membrane of the gastrointestinal tract, around the lymphatic vessels, around the blood vessels and the brain, and have abundant granules in the cytoplasm.
알러지 반응은 집먼지진드기, 꽃가루, 동물 비듬, 곰팡이, 난알부민, 우유단백질, 땅콩 등의 알러지원에 대항하기 위하여 생성된 IgE가 비만세포에 작용함으로써 야기된다(Wills-Karp M., et al., Science, 282, pp 2258-61, 1998; Grunig G., et al., Science, 282, pp 2261-2263, 1998). Allergic reactions are caused by the action of IgE produced against mite allergens such as house dust mite, pollen, animal dandruff, fungi, egg albumin, milk protein, and peanut on mast cells (Wills-Karp M., Science, 282, pp 2258-61, 1998; Grunig G., et al., Science, 282, pp 2261-2263, 1998).
알러지원이 생체에 침입하면 알러지원은 먼저 항원제시세포에 의해 인지되며, 이 항원제시세포는 IL-4 존재하에서 알러지원 제시를 통해 Th0를 Th2 세포로 분화시킨다. 이렇게 분화된 Th2 세포는 IL-4, IL-5, IL-13와 같은 사이토카인을 분비하는데, IL-4, IL-5 등이 B세포에 작용하여 IgE의 생성을 유도한다(Kato, Y. et al., J. Immuno. 1999, 162, 7470-7479; Toru, H. et al., J. Allergy. Clin. Immunol. 1998, 102, 491-502).When the allergen enters the living body, the allergen is first recognized by the antigen presenting cell, and this antigen-presenting cell differentiates Th0 into Th2 cells through the presentation of allergen in the presence of IL-4. These differentiated Th2 cells secrete cytokines such as IL-4, IL-5 and IL-13, and IL-4 and IL-5 act on B cells to induce IgE production (Kato, Y. et al. et al., J. Immuno 1999, 162, 7470-7479; Toru, H. et al., J. Allergy. Clin. Immunol 1998, 102, 491-502).
IgE는 비만세포의 고친화도 IgE 수용체인 FcεRⅠ에 결합하는데, 알러지원이 비만세포의 FcεRⅠ와 결합된 IgE에 결합하여 이들 수용체들의 교차결합을 일으키고, 이것이 신호로서 작용하여 일련의 신호전달 반응이 진행되게 된다(Marshall, J. S. Nat. Rev. Immunol. 2004, 4, 787-799).IgE binds to the IgE receptor, FcεR I, which binds to IgE bound to FcεR I of mast cells and causes cross-linking of these receptors, which acts as a signal and leads to a series of signal transduction (Marshall, JS Nat. Rev. Immunol., 2004, 4, 787-799).
이 신호전달 반응을 통해서 비만세포가 활성화되면 세포의 과립 내에 존재하던 화학매개체들인 히스타민(histamine), 프로테오글리칸(proteoglycan), TNF-α 등이 분비되며, 또 세포막 인지질에서 유리된 아라키돈산 대사를 통해 류코트리엔(leukotriens)과 프로스타글라딘(prostaglandins)와 같은 염증 매개물질을 생성한다(Nadler, M. J. et al., Adv. Immunol. 2004, 76, 325-355).이들 물질들은 혈관 확장이나 투과성의 항진, 신경종말의 자극, 점액 분비의 항진, 평활근의 수축 등 일련의 알러지 염증 반응을 매개한다고 알려져 있다(Meltzer, E. O. et al., Ann Allergy Asthma Immunnol. 2000, 84, 176-187).When the mast cells are activated through the signal transduction reaction, histamine, proteoglycan and TNF-α, which are the chemical mediators present in the cell granules, are secreted and arachidonic acid metabolism liberated from the cell membrane phospholipids causes leukotriene (Nadler, MJ et al., Adv. Immunol., 2004, 76, 325-355). These substances are involved in vasodilatation or hyperpermeability, (Meltzer, EO et al., 2000, 84, 176-187), which is known to mediate a series of allergic inflammatory responses such as stimulation of nerve endings, exacerbation of mucus secretion, and contraction of smooth muscle.
항히스타민제, 류코트리엔 길항제, 항-IgE 항체, IgE의 합성과 분비를 저해하는 물질(예컨대 미국 특허 제6,369,091호가 개시하는 디아실벤지미다졸 동족체 등) 등이 알러지성 증상을 개선할 수 있다는 사실이 상기 기작을 뒷받침한다.The fact that substances that inhibit the synthesis and secretion of IgE, such as antihistamines, leukotriene antagonists, anti-IgE antibodies, and the like (for example, diacylbenzimidazole analogues disclosed in U.S. Patent No. 6,369,091) It supports the mechanism.
본 발명은 밀겨 추출물로 분리될 수 있는 유효물질이 비만세포의 활성화 등을 억제함을 확인함으로써 완성된 것이다.
The present invention has been completed by confirming that the active substance which can be separated by the push-back extract inhibits the activation of mast cells and the like.
본 발명의 목적은 알러지성 질환의 개선제 조성물을 제공하는 데 있다.It is an object of the present invention to provide an ameliorative agent composition for allergic diseases.
본 발명의 다른 목적이나 구체적인 목적은 이하에서 제시될 것이다.
Other and further objects of the present invention will be described below.
본 발명자들은 아래의 실시예 및 실험예에서 확인되는 바와 같이, 밀겨(Wheat Bran) 추출물로부터 분리한 5-n-노나데실레조시놀(5-n-nonadecylresorcinol)과 5-n-헤네코실레조시놀(5-n-heneicosylresorcinol)이 IgE 및 항원(DNP-BSA)으로 활성화시킨 비만세포주 RBL-2H3(rat basophilic leukemia)에 처리한 결과, 베타-헥소사미니다아제(β-hexosaminidase)의 생성이 억제됨을 확인할 수 있었다. 상기 비만세포주인 RBL-2H3는 그 표면에 IgE 항체의 수용체(FcεRI)를 갖고 있어 IgE와 항원으로 활성화되면 탈과립 등에 의하여 히스타민 등의 알러지 반응의 매개물질을 분비하는 것으로 알려져 있는 세포이며, 베타-헥소사미니다아제는 탈과립의 지표 물질로 알려져 있는 물질이다(J. Korean Soc. Appl. Biol. Chem. 48(4), 315-321(2005)). 본 발명자들은 또한 밀겨 추출물로부터 분리한 5-n-노나데실레조시놀과 5-n-헤네코실레조시놀이 TNF-α, IL-4, IL-6, IL-10 등의 알러지 반응과 염증 반응에 관여하는 사이토카인의 생성을 억제함을 확인할 수 있었으며, 나아가 p-AKT의 생성을 억제함을 확인할 수 있었다. p-AKT는 phosphoinositol 3-kinase(PI3K)를 매개로 비만세포의 증식과 사이토카인의 생성에 관여하는 것으로 알려져 있다(Huang, F. et al., Int. Immunopharmacol. 2008, 8, 502-507).As shown in the following Examples and Experimental Examples, the present inventors have found that 5-n-nonadecylresorcinol isolated from Wheat Bran extract and 5-n-nonadecylresorcinol, Treatment of 5-n-heneicosylresorcinol with an IgE and antigen (DNP-BSA) -activated mast cell line RBL-2H3 (rat basophilic leukemia) inhibited the formation of β-hexosaminidase . The above-mentioned mast cell line, RBL-2H3, has a receptor of IgE antibody on its surface (FcεRI) and is known to secrete mediators of allergic reactions such as histamine by IgE and degranulation when it is activated as an antigen. Beta-hex Sasami is a substance known as an indicator substance of degranulation (J. Korean Soc. Appl. Biol. Chem. 48 (4), 315-321 (2005)). The present inventors also found that 5-n-nonadecylzocinol and 5-n-henecyl silezocinol isolated from the wheat extract inhibited allergic and inflammatory reactions such as TNF-α, IL-4, IL-6 and IL- , And inhibited the production of p-AKT. Furthermore, it was confirmed that the inhibition of the production of p-AKT was suppressed. p-AKT is known to be involved in the proliferation of mast cells and the production of cytokines via phosphoinositol 3-kinase (PI3K) (Huang, F. et al., Int. Immunopharmacol. 2008, 8, 502-507) .
본 발명은 전술한 바의 실험 결과에 기초하여 완성된 것으로서, 본 발명의 알러지성 질환의 개선제 조성물은 밀겨 추출물로부터 분리될 수 있는 5-n-노나데실레조시놀 또는 5-n-헤네코실레조시놀을 유효성분으로 포함함을 특징으로 한다.The present invention has been completed on the basis of the above-described experimental results. The inventive allergic disease remedy composition comprises 5-n-nonadecylresorcinol or 5-n-henecosyl And contains joshinol as an active ingredient.
상기 5-n-노나데실레조시놀 및 5-n-헤네코실레조시놀은 문헌(J Bacteriol . 1996 July; 178(14): 4027-4030; J. Agric . Food Chem. 2003, 51, 6683-6688; Chem. Pharm . Bull. 1989, 37, 2431-2434; Biosci . Biotech . Biochem . 1997, 61, 480-486) 등에서 보고된 바 있는 공지의 물질이며, 그것의 IUPAC 명칭 및 그것의 화학식은 아래의 [화학식 1] 및 [화학식 2]에서 각각 확인할 수 있다.The 5-n-nonadecylzosinol and 5-n-henecyl silezocinol are described in J. Bacteriol . 1996 July; 178 (14): 4027-4030; J. Agric . Food Chem . 2003, 51 , 6683-6688; Chem. Pharm . Bull . 1989, 37 , 2431-2434; Biosci . Biotech . Biochem . 1997, 61 , 480-486), and its IUPAC name and its chemical formula can be confirmed by the following formulas (1) and (2), respectively.
본 명세서에서, 상기 "밀겨"는 밀(wheat)을 도정하는 과정에서 얻어지는 부산물을 의미한다. 이러한 부산물은 통상 밀가루가 되는 배유를 제외하고 과피(종자의 껍질)와 배아로 구성되거나, 배아가 밀의 도정 과정에서 배유와 함께 분리될 경우에는 주로 과피로 구성되게 된다. 밀겨는 소량의 배유와 배아를 포함할 수 있다. 밀겨를 분쇄하여 얻은 밀겨 분말은 입자도에 따라 밀기울, 말분, 정강, 등외밀가루 등으로 다시 세분하기도 하는데, 본 명세서에서는 "밀겨"는 이러한 밀겨 분말로부터 유래한 상기 밀기울, 말분, 정강, 등외밀가루 등을 포함하는 의미이다. In this specification, the term "pushing" means a by-product obtained in the process of rolling wheat. These by-products usually consist of pericarp (shell of the seed) and embryo, except for the ending oil, or when the embryo is separated with the endive oil during the process of milling, it mainly consists of pericarp. Pushing may include small amounts of endosperm and embryo. The pressed powder obtained by grinding wheat bran can be subdivided into wheat bran, wheat flour, horse chestnut, cane flour, etc. according to the grain size. In the present specification, "wheat bran" refers to wheat flour, horse chunks, It is meant to include.
또한 본 명세서에서, 상기 "추출물"이란 물, 메탄올, 에탄올, 부탄올 등의 탄소수 1 내지 4의 저급 알콜, 에틸렌, 아세톤, n-헥산, 에테르, 클로로포름, 에틸아세테이트, 부틸아세테이트, 디클로로메탄, N, N-디메틸포름아미드(DMF), 디메틸설폭사이드(DMSO), 1,3-부틸렌글리콜, 프로필렌글리콜 또는 이들의 혼합 용매를 사용하여 얻어진 조추출물과 그 추출물을 상기 열거한 용매 중 하나 이상으로 분획하여 얻어진 분획물을 말한다. 추출 방법은 유효성분의 추출 정도, 보존 정도를 고려하여 냉침, 환류, 가온, 초음파 방사 등 임의의 방식을 적용될 수 있다. 분획된 추출물의 경우 상기 조추출물을 특정 용매에 현탁시킨 후 극성이 다른 용매와 혼합·정치시켜 얻은 분획물, 상기 조추출물을 실리카겔 등이 충진된 칼럼에 흡착시킨 후 소수성 용매, 친수성 용매 또는 이들의 혼합 용매를 이동상으로 하여 얻은 분획물을 포함하는 의미이다. 또한 상기 추출물의 의미에는 동결건조, 진공건조, 열풍건조, 분무건조 등의 방식으로 추출 용매가 제거된 농축된 액상의 추출물 또는 고형상의 추출물이 포함된다. 바람직하게는 상기 "추출물"은 에탄올을 추출 용매로 사용하여 얻은 추출물 또는 그 에탄올 추출물을 물과 n-헥산으로 용매 분획하여 얻어지는 n-헥산층의 분획물을 의미한다. In the present specification, the "extract" includes water, lower alcohol having 1 to 4 carbon atoms such as methanol, ethanol and butanol, ethylene, acetone, n-hexane, ether, chloroform, ethyl acetate, butyl acetate, dichloromethane, The crude extract obtained by using N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), 1,3-butylene glycol, propylene glycol or a mixed solvent thereof and the extract thereof are fractionated into one or more of the above- And the like. The extraction method can be applied by any method such as cold-rolling, refluxing, heating, ultrasonic irradiation or the like in consideration of the degree of extraction and the degree of preservation of the active ingredient. In the case of the fractionated extract, the crude extract is suspended in a specific solvent, and the fractions obtained by mixing and leaving with a solvent having a different polarity are adsorbed on a column packed with silica gel or the like, and a hydrophobic solvent, a hydrophilic solvent or a mixture thereof Quot; means a fraction obtained by using a solvent as a mobile phase. Also, the meaning of the extract includes a concentrated liquid extract or a solid extract in which the extraction solvent is removed by a method such as freeze drying, vacuum drying, hot air drying, spray drying and the like. Preferably, the "extract" means a fraction of an n-hexane layer obtained by solvent fractionation of an extract obtained by using ethanol as an extraction solvent or an ethanol extract thereof with water and n-hexane.
또 본 명세서에서, 상기 "유효성분"의 의미는 단독으로 목적하는 활성을 나타내거나 또는 그 자체는 활성이 없는 담체와 함께 활성을 나타낼 수 있는 성분을 의미한다.In the present specification, the above-mentioned "active ingredient" means an ingredient that exhibits the desired activity alone or can exhibit activity together with a carrier that is itself inactive.
또 본 명세서에서, 상기 "알러지성 질환"은 비만세포의 탈과립 등 비만세포의 활성화에 의하여 야기되는 알러지 반응으로 인하여 초래되는 임상적 증상을 의미하는데, 이러한 임상적 증상에는 접촉성 피부염, 아토피성 피부염, 습진, 소양(搔痒), 화분증, 천식, 기관지염, 두드러기, 혈관염, 비염, 위장증, 설사, 간질성 폐렴, 관절염, 안염, 결막염, 신경염, 중이염, 육아종증, 뇌척수염, 방광염, 후두염, 자반병(紫斑病), 음식물 알러지, 곤충 알러지, 약물 알러지, 금속 알러지, 아나필락시성 쇼크(anaphylactic shock) 등이 포함된다(Bierman CW, et al.(eds.) Allergy, asthma, and immunology from infancy to adulthood. page xvii, Saunders, Philadelphia, 1996).In the present specification, the "allergic disease" refers to a disease caused by activation of mast cells such as degranulation of mast cells Refers to a clinical symptom resulting from an allergic reaction which includes but is not limited to contact dermatitis, atopic dermatitis, eczema, pruritus, hay fever, asthma, bronchitis, urticaria, vasculitis, rhinitis, Anaphylactic shock, and the like, all of which may be caused by, for example, inflammatory bowel disease, interstitial pneumonia, arthritis, eye inflammation, conjunctivitis, neuritis, otitis media, granulomatosis, encephalomyelitis, cystitis, laryngitis, purpura, (Bierman CW, et al. (Eds.) Allergy, Asthma, and Immunology from infancy to adulthood, page xvii, Saunders, Philadelphia, 1996).
또 본 명세서에서, 상기 "개선"이란 병리적 증상의 예방, 치료, 발병 억제, 또는 지연을 의미한다.In the present specification, the "improvement" means prevention, treatment, suppression of onset or delay of pathological symptoms.
한편 본 발명의 조성물은 그 유효성분인 상기 [화학식 1] 또는 [화학식 2]의 화합물을 용도, 제형, 배합 목적 등에 따라 치료를 의도하는 알러지성 질환의 개선 활성을 나타낼 수 있는 한 임의의 양(유효량)으로 포함할 수 있는데, 통상적인 유효량은 조성물 전체 중량을 기준으로 할 때 0.001 중량 % 내지 15 중량 % 범위 내에서 결정될 것이다. 여기서 "유효량"이란 그 적용 대상인 포유동물 바람직하게는 사람에게서, 알러지성 질환의 개선, 치료, 또는 그러한 병리적 증상의 발병 억제/지연을 유도할 수 있는 유효성분의 양을 말한다. 이러한 유효량은 당업자의 통상의 능력 범위 내에서 실험적으로 결정될 수 있다.In addition, the composition of the present invention can be used as an active ingredient of the present invention, as long as it can exhibit the improving activity of an allergic disease intended to be treated according to the purpose of use, formulation, Effective amount will generally be determined within the range of from 0.001% to 15% by weight based on the total weight of the composition. The term "effective amount" as used herein refers to the amount of active ingredient capable of inducing the improvement, treatment, or inhibition / delay of onset of an allergic disease or the onset of such pathological condition in a mammal, preferably a human, to which it is applied. Such effective amounts can be determined experimentally within the ordinary skill of those skilled in the art.
다른 측면에 있어서, 본 발명은 상기 [화학식 1] 또는 [화학식 2]의 화합물을 유효성분으로 포함하는 염증성 질환의 개선제 조성물에 관한 것이다.In another aspect, the present invention relates to an agent composition for improving inflammatory diseases, which comprises the compound of the formula (1) or (2) as an active ingredient.
IgE 및 그것의 항원에 의하여 활성화된 비만세포는 탈과립에 의하여 알러지 반응을 일으키는 히스타민 등을 분비할 뿐만 아니라 프로스타글란딘, 류코트리엔, TNF-α, IL-1β, IL-4, IL-5, IL-6, IL-13 등의 사이토카인을 합성하고 분비한다. 프로스타글라딘, 류코트리엔은 COX나 리폭시게나제(lipooxygenase)에 의해 아라키돈산으로부터 생성되는 염증 매개 물질이고, TNF-α, IL-1β, IL-6 등은 대표적인 염증성 사이토카인이다(Thomas. R., Rev. Physiol. Biochem. Pharmacol., 100, 1984). 상기 프로스타글란딘 등은 염증 부위로의 백혈구의 이주를 촉진하며, 상기 염증성 사이토카인은 세포 독성과 각종 염증 반응을 일으키는 NO를 생성하는 iNOS의 발현과 염증과 통증에 관여하는 COX-2의 발현을 유도한다. 또한 IL-3, IL-5, IL-13 등은 만성 알러지성 염증을 매개하는 호산구의 침윤과 활성화를 일으키는 것으로 알려져 있다(Erb KJ., Immunol. Today, 20, pp 317-322, 1999; Rothenberg ME., Eosinophilia., N. Engl. Med. , 338, pp 1592-1600, 1998).IgE and its antigen-activated mast cells secrete histamine and the like, which cause allergic reactions by degranulation, as well as secretion of prostaglandins, leukotrienes, TNF-α, IL-1β, IL-4, IL- IL-13 and other cytokines. Prostaglandins and leukotrienes are inflammatory mediators produced from arachidonic acid by COX or lipooxygenase, and TNF-α, IL-1β, IL-6 and the like are representative inflammatory cytokines (Thomas R. et al. , Rev. Physiol. Biochem. Pharmacol., 100, 1984). The prostaglandin and the like promote migration of white blood cells to the inflammation site, and the inflammatory cytokine induces the expression of iNOS, which produces NO which causes cytotoxicity and various inflammatory responses, and the expression of COX-2, which is involved in inflammation and pain . In addition, IL-3, IL-5, and IL-13 are known to cause invasion and activation of eosinophils that mediate chronic allergic inflammation (Erb KJ, Immunol. Today, 20, pp 317-322, 1999; Rothenberg ME., Eosinophilia., N. Engl. Med., 338, pp 1592-1600, 1998).
아래의 실험예는 상기 [화학식 1] 또는 [화학식 2]의 화합물이 활성화된 비만세포의 염증성 사이토카인의 생성을 억제할 뿐만 아니라 COX-2의 발현을 억제함을 보여준다. 그리고 염증성 사이토카인의 전사인자인 NF-κB의 생성 억제 활성과 NF-κB의 활성화에 관여하는 MAPK(mitogen-activated protein kinase)(ERK, JNK 및 p-38)의 생성 억제 활성을 보여주며, 또 리폭시게나제의 활성도 억제함을 보여준다.The following experimental examples show that the compound of the above formula (1) or (2) inhibits the production of inflammatory cytokines and inhibits the expression of COX-2 in activated mast cells. (ERK, JNK, and p-38), which is involved in the activation of NF-κB and the activation of NF-κB, which is a transcription factor of inflammatory cytokines. Lt; / RTI > inhibits the activity of lipoxygenase.
이러한 실험 결과는 상기 [화학식 1] 또는 [화학식 2]의 화합물이 염증성 질환의 개선제로서도 유용하게 사용될 수 있음을 보여주는 것이라 할 수 있다.These experimental results show that the compound of formula (1) or (2) can be usefully used as an agent for improving inflammatory diseases.
본 명세서에서, 상기 "염증성 질환"이란 외부의 물리·화학적 자극 또는 박테리아, 곰팡이, 바이러스, 각종 알러지 유발 물질 등 외부 감염원의 감염에 대한 국부적 또는 전신적 생체 방어 반응으로 특정되는 어떠한 상태로서 정의될 있다. 이러한 반응은 각종 염증 매개 인자와 면역세포와 관련된 효소(예컨대 iNOS, COX-2 등) 활성화, 염증 매개 물질의 분비(예컨대, NO, TNF-α, IL-6, IL-1β, PGE2의 분비), 체액 침윤, 세포 이동, 조직 파괴 등의 일련의 복합적인 생리적 반응을 수반하며, 홍반, 통증, 부종, 발열, 신체의 특정 기능의 저하 또는 상실 등의 증상에 의해 외적으로 나타난다. 상기 염증성 질환은 급성, 만성, 궤양성, 알러지성 또는 괴사성을 띨 수 있으므로, 어떠한 질환이 상기와 같은 염증성 질환의 정의에 포함되는 한 그것이 급성이든지, 만성이든지, 궤양성이든지, 알러지성이든지 또는 괴사성이든지를 불문한다. 구체적으로 상기 염증성 질환에는 천식, 알러지성 및 비-알러지성 비염, 만성 및 급성 비염, 만성 및 급성 위염 또는 장염, 궤양성 위염, 급성 및 만성 신장염, 급성 및 만성 간염, 만성 폐쇄성 폐질환, 폐섬유증, 과민성 대장 증후군, 염증성 통증, 편두퐁, 두통, 허리 통증, 섬유 근육통, 근막 질환, 바이러스 감염(예컨대, C형 감염), 박테리아 감염, 곰팡이 감염, 화상, 외과적 또는 치과적 수술에 의한 상처, 프로스타글라딘 E 과다 증후군, 아테롬성 동맥 경화증, 통풍, 관절염, 류머티스성 관절염, 강직성 척추염, 호지킨병, 췌장염, 결막염, 홍채염, 공막염, 포도막염, 피부염(아토피성 피부염 포함), 습진, 다발성 경화증 등이 포함될 것이다. In the present specification, the above-mentioned "inflammatory disease" is defined as any state specified by a local or systemic bio-defense reaction against external physical or chemical stimuli or infections of external infectious agents such as bacteria, fungi, viruses and allergens. This reaction is enzyme secretion (e.g., iNOS, COX-2, etc.) activation, release of inflammatory mediators (e. G., NO, TNF-α, IL -6, IL-1β, PGE 2 related to various inflammatory mediators and the immune cells ), Bodily fluid infiltration, cell migration, and tissue destruction, and manifest externally by symptoms such as erythema, pain, edema, fever, deterioration or loss of specific function of the body. The inflammatory disease may be acute, chronic, ulcerative, allergic or necrotic, so that as long as any disease is included in the definition of inflammatory diseases as described above, it may be acute, chronic, ulcerative, Whether it is necrotic or not. Specifically, the inflammatory diseases include asthma, allergic and non-allergic rhinitis, chronic and acute rhinitis, chronic and acute gastritis or enteritis, ulcerative gastritis, acute and chronic nephritis, acute and chronic hepatitis, chronic obstructive pulmonary disease, Inflammatory bowel syndrome, inflammatory pain, migraine headache, headache, back pain, fibromyalgia, fascia disease, viral infection (e.g., C type infection), bacterial infection, fungal infection, burn, wound due to surgical or dental surgery, Rheumatoid arthritis, ankylosing spondylitis, Hodgkin's disease, pancreatitis, conjunctivitis, iritis, scleritis, uveitis, dermatitis (including atopic dermatitis), eczema, multiple sclerosis, etc. Will be included.
본 발명의 염증성 질환의 개선제 조성물에 있어서, 개선의 의미, 유효량 등과 관련하여서는 상기 본 발명의 알러지성 질환의 개선제 조성물과 관련하여 설명한 바가 그대로 유효하다. With regard to the meaning, effective amount, etc. of improvement in the composition for improving inflammatory diseases according to the present invention, as described in relation to the composition for improving an allergic disease of the present invention is effective as it is.
본 발명의 알러지성 질환의 개선제 조성물과 염증성 질환의 개선제 조성물(이하 "본 발명의 조성물")은 구체적인 양태에 있어서는 약제학적 조성물로 이용될 수 있다.The composition of the present invention for improving allergic diseases and the composition for improving inflammatory diseases (hereinafter referred to as "the composition of the present invention ") may be used as a pharmaceutical composition in a specific embodiment.
본 발명의 약제학적 조성물은 유효성분 이외에 약제학적으로 허용되는 담체, 부형제 등을 포함하여, 경구용 제형(정제, 현탁액, 과립, 에멀젼, 캡슐, 시럽 등), 비경구형 제형(멸균 주사용 수성 또는 유성 현탁액), 국소형 제형(용액, 크림, 연고, 겔, 로션, 패치) 등으로 제조될 수 있다.The pharmaceutical composition of the present invention may be in a form suitable for oral use (tablets, suspensions, granules, emulsions, capsules, syrups, etc.), parenteral formulations (sterile injectable aqueous or non- Ointments, ointments, solutions, creams, ointments, gels, lotions, patches, and the like).
상기에서 "약제학적으로 허용되는" 의미는 유효성분의 활성을 억제하지 않으면서 적용(처방) 대상이 적응가능한 이상의 독성(충분히 낮은 독성)을 지니지 않는다 의미이다.The term "pharmaceutically acceptable" as used herein means that the application (prescribing) subject does not have the above-mentioned toxicity (sufficiently low toxicity) without inhibiting the activity of the active ingredient.
약제학적으로 허용되는 담체의 예로서는 락토스, 글루코스, 슈크로스, 전분(예컨대 옥수수 전분, 감자 전분 등), 셀룰로오스, 그것의 유도체(예컨대 나트륨 카르복시메틸 셀룰로오스, 에틸셀룰로오스, 등) 맥아, 젤라틴, 탈크, 고체 윤활제(예컨대 스테아르산, 스테아르산 마그네슘 등), 황산 칼슘, 식물성 기름(예컨대 땅콩 기름, 면실유, 참기름, 올리브유 등), 폴리올(예컨대 프로필렌 글리콜, 글리세린 등), 알긴산, 유화제(예컨대 TWEENS), 습윤제(예컨대 라우릴 황산 나트륨), 착색제, 풍미제, 정제화제, 안정화제, 항산화제, 보존제, 물, 식염수, 인산염 완충 용액 등을 들 수 있다. 이러한 담체는 본 발명의 약제학적 조성물의 제형에 따라 적당한 것을 하나 이상 선택하여 사용할 수 있다.Examples of pharmaceutically acceptable carriers include lactose, glucose, sucrose, starch (e.g. corn starch, potato starch, etc.), cellulose, derivatives thereof (e.g. sodium carboxymethylcellulose, ethylcellulose, etc.) malt, gelatin, talc, (E.g., peanut oil, cottonseed oil, sesame oil, olive oil, etc.), polyol (e.g., propylene glycol, glycerin and the like), alginic acid, emulsifiers (e.g., TWEENS), humectants Such as sodium lauryl sulfate, a coloring agent, a flavoring agent, a tableting agent, a stabilizer, an antioxidant, a preservative, water, a saline solution, and a phosphate buffer solution. The carrier may be selected from one or more of suitable pharmaceutical formulations according to the formulation of the pharmaceutical composition of the present invention.
부형제도 본 발명의 약제학적 조성물의 제형에 따라 적합한 것을 선택하여 사용할 수 있는데, 예컨대 본 발명의 약제학적 조성물이 수성 현탁제로 제조될 경우에 적합한 부형제로서는 나트륨 카르복시메틸 셀룰로오스, 메틸 셀룰로오스, 히드로프로필메틸셀룰로오스, 알긴산 나트륨, 폴리비닐피롤리돈 등의 현탁제나 분산제 등을 들 수 있다. 주사액으로 제조되는 경우 적합한 부형제로서는 링거액, 등장 염화나트륨 등을 들 수 있다.The excipient may be selected according to the formulation of the pharmaceutical composition of the present invention. For example, when the pharmaceutical composition of the present invention is prepared by an aqueous suspension, suitable excipients include sodium carboxymethylcellulose, methylcellulose, hydropropylmethylcellulose , Sodium alginate, polyvinylpyrrolidone, and the like. Suitable excipients when prepared from injection solutions include Ringer's solution, isotonic sodium chloride, and the like.
본 발명의 약제학적 조성물은 경구 또는 비경구로 투여될 수 있고, 경우에 따라서는 국소적으로 투여될 수 있다.The pharmaceutical composition of the present invention can be administered orally or parenterally, and in some cases, can be administered topically.
본 발명의 약제학적 조성물은 그 1일 투여량이 통상 0.001 ~ 150 mg/kg 체중 범위이고, 1회 또는 수회로 나누어 투여할 수 있다. 그러나, 본 발명의 약제학적 조성물의 투여량은 투여 경로, 환자의 연령, 성별, 체중, 환자의 중증도 등의 여러 관련 인자에 비추어 결정되는 것이므로 상기 투여량은 어떠한 측면으로든 본 발명의 범위를 제한하는 것으로 이해되어서는 아니 된다. The daily dose of the pharmaceutical composition of the present invention is usually 0.001 to 150 mg / kg body weight, and may be administered once or several times. However, since the dosage of the pharmaceutical composition of the present invention is determined in view of various related factors such as route of administration, age, sex, weight, and patient's severity of the patient, the dose is limited in any aspect to the scope of the present invention Should not be understood to be.
본 발명의 조성물은 다른 구체적인 양태에 있어서, 식품 조성물로서 파악할 수 있다.In another specific embodiment, the composition of the present invention can be identified as a food composition.
본 발명의 식품 조성물은 건강 보조식품, 특수 영양 보충용 식품, 기능성 음료 등으로 제조될 수 있다.The food composition of the present invention can be produced as a health supplement food, a special nutrition supplement food, a functional beverage and the like.
본 발명의 식품 조성물에는 그 유효성분 이외에 감미제, 풍미제, 생리활성 성분, 미네랄 등이 포함될 수 있다.The food composition of the present invention may contain sweetening agents, flavoring agents, physiologically active ingredients, minerals and the like in addition to the active ingredients thereof.
감미제는 식품이 적당한 단맛을 나게 하는 양으로 사용될 수 있으며, 천연의 것이거나 합성된 것일 수 있다. 바람직하게는 천연 감미제를 사용하는 경우인데, 천연 감미제로서는 옥수수 시럽 고형물, 꿀, 수크로오스, 프룩토오스, 락토오스, 말토오스 등의 당 감미제를 들 수 있다. Sweetening agents may be used in an amount that sweetens the food in a suitable manner, and may be natural or synthetic. Preferably, natural sweeteners are used. Examples of natural sweeteners include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose and maltose.
풍미제는 맛이나 향을 좋게 하기 위하여 사용될 수 있는데, 천연의 것과 합성된 것 모두 사용될 수 있다. 바람직하게는 천연의 것을 사용하는 경우이다. 천연의 것을 사용할 경우에 풍미 이외에 영양 강화의 목적도 병행할 수 있다. 천연 풍미제로서는 사과, 레몬, 감귤, 포도, 딸기, 복숭아 등에서 얻어진 것이거나 녹차잎, 둥굴레, 대잎, 계피, 국화 잎, 자스민 등에서 얻어진 것일 수 있다. 또 인삼(홍삼), 죽순, 알로에 베라, 은행 등에서 얻어진 것을 사용할 수 있다. 천연 풍미제는 액상의 농축액이나 고형상의 추출물일 수 있다. 경우에 따라서 합성 풍미제가 사용될 수 있는데, 합성 풍미제는 에스테르, 알콜, 알데하이드, 테르펜 등이 이용될 수 있다. Flavors may be used to enhance taste or flavor, both natural and synthetic. Preferably, a natural one is used. When using natural ones, the purpose of nutritional fortification can be performed in addition to the flavor. Examples of natural flavoring agents include those obtained from apples, lemons, citrus fruits, grapes, strawberries, peaches, and the like, or those obtained from green tea leaves, Asiatica, Daegu, Cinnamon, Chrysanthemum leaves and Jasmine. Also, those obtained from ginseng (red ginseng), bamboo shoots, aloe vera, banks and the like can be used. The natural flavoring agent may be a liquid concentrate or a solid form of extract. Synthetic flavors may be used depending on the case, and synthetic flavors such as esters, alcohols, aldehydes, terpenes and the like may be used.
생리 활성 물질로서는 카테킨, 에피카테킨, 갈로가테킨, 에피갈로카테킨 등의 카테킨류나, 레티놀, 아스코르브산, 토코페롤, 칼시페롤, 티아민, 리보플라빈 등의 비타민류 등이 사용될 수 있다.Examples of the physiologically active substance include catechins such as catechin, epicatechin, gallocatechin and epigallocatechin, and vitamins such as retinol, ascorbic acid, tocopherol, calciferol, thiamine and riboflavin.
미네랄로서는 칼슘, 마그네슘, 크롬, 코발트, 구리, 불소화물, 게르마늄, 요오드, 철, 리튬, 마그네슘, 망간, 몰리브덴, 인, 칼륨, 셀레늄, 규소, 나트륨, 황, 바나듐, 아연 등이 사용될 수 있다.As the mineral, calcium, magnesium, chromium, cobalt, copper, fluoride, germanium, iodine, iron, lithium, magnesium, manganese, molybdenum, phosphorus, potassium, selenium, silicon, sodium, sulfur, vanadium and zinc can be used.
또한 본 발명의 식품 조성물은 상기 감미제 등 이외에도 필요에 따라 보존제, 유화제, 산미료, 점증제 등을 포함할 수 있다. In addition, the food composition of the present invention may contain preservatives, emulsifiers, acidifiers, thickeners and the like as needed in addition to the above sweeteners.
이러한 보존제, 유화제 등은 그것이 첨가되는 용도를 달성할 수 있는 한 극미량으로 첨가되어 사용되는 것이 바람직하다. 극미량이란 수치적으로 표현할 때 식품 조성물 전체 중량을 기준으로 할 때 0.0005중량% 내지 약 0.5중량% 범위를 의미한다.Such preservatives, emulsifiers and the like are preferably added in a very small amount as long as they can attain an application to which they are added. The term " trace amount " means, when expressed numerically, in the range of 0.0005% by weight to about 0.5% by weight based on the total weight of the food composition.
사용될 수 있는 보존제로서는 소듐 소르브산칼슘, 소르브산나트륨, 소르브산칼륨, 벤조산칼슘, 벤조산나트륨, 벤조산칼륨, EDTA(에틸렌디아민테트라아세트산) 등을 들 수 있다. Examples of the preservative which can be used include calcium sodium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate and EDTA (ethylenediaminetetraacetic acid).
사용될 수 있는 유화제로서는 아카시아검, 카르복시메틸셀룰로스, 잔탄검, 펙틴 등을 들 수 있다.Examples of the emulsifier which can be used include acacia gum, carboxymethyl cellulose, xanthan gum, pectin and the like.
사용될 수 있는 산미료로서는 연산, 말산, 푸마르산, 아디프산, 인산, 글루콘산, 타르타르산, 아스코르브산, 아세트산, 인산 등을 들 수 있다. 이러한 산미료는 맛을 증진시키는 목적 이외에 미생물의 증식을 억제할 목적으로 식품 조성물이 적정 산도로 되도록 첨가될 수 있다.Examples of the acidulant that can be used include acid, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, and phosphoric acid. Such an acidulant may be added so that the food composition has a proper acidity for the purpose of inhibiting the growth of microorganisms other than the purpose of enhancing the taste.
사용될 수 있는 점증제로서는 현탁화 구현제, 침강제, 겔형성제, 팽화제 등을 들 수 있다. Agents that may be used include suspending agents, sedimentation agents, gel formers, bulking agents and the like.
본 발명의 조성물은 구체적인 양태에 있어서 화장품 조성물로 파악할 수 있다. The composition of the present invention can be identified as a cosmetic composition in a specific embodiment.
본 발명의 조성물이 화장품 조성물로서 파악될 경우, 그 화장품 조성물은 다양한 형태로 제조될 수 있는데, 예컨대, 에멀젼, 로션, 크림(수중유적형, 유중수적형, 다중상), 용액, 현탁액(무수 및 수계), 무수 생성물(오일 및 글리콜계), 젤, 마스크, 팩, 분말 등의 제형으로 제조될 수 있다.When the composition of the present invention is recognized as a cosmetic composition, the cosmetic composition may be prepared in various forms, for example, emulsion, lotion, cream (oil-in-water type, oil water type, multiphase), solution, suspension (Water and water), anhydrous products (oil and glycol), gel, mask, pack, powder and the like.
본 발명의 조성물은 그 유효성분을 포함하는 이외에 화장품 제제에 있어서 수용가능한 담체를 포함할 수 있다. The composition of the present invention may contain an acceptable carrier in cosmetic preparations other than those containing the active ingredient.
여기서 "화장품 제제에 있어서 수용가능한 담체"란 화장품 제제에 포함될 수 있는 이미 공지되어 사용되고 있는 화합물 또는 조성물이거나 앞으로 개발될 화합물 또는 조성물로서 피부와의 접촉시 인체가 적응 가능한 이상의 독성을 지니지 않는 것을 말한다.As used herein, the term " acceptable carrier for cosmetic preparation "refers to a compound or composition which is already known and used in cosmetics, or which is a compound or composition to be developed in the future, and which has no toxicity that the human body can adapt to when contacted with skin.
상기 담체는 본 발명의 조성물에 그것의 전체 중량에 대하여 약 1 중량 % 내지 약 99.99 중량 %, 바람직하게는 조성물의 중량의 약 50 중량% 내지 약 99 중량 %로 포함될 수 있다. The carrier may be included in the composition of the present invention in an amount of from about 1% by weight to about 99.99% by weight, preferably from about 50% by weight to about 99% by weight of the composition, based on the total weight thereof.
그러나 상기 비율은 화장품의 전술한 바의 제형에 따라 또 그것의 구체적인 적용 부위(얼굴이나 손)나 그것의 바람직한 적용량 등에 따라 달라지는 것이기 때문에, 상기 비율은 어떠한 측면으로든 본 발명의 범위를 제한하는 것으로 이해되어서는 안 된다. However, since the ratio depends on the above-mentioned formulation of the cosmetic product and its specific application site (face or hands) or the desired amount of application thereof, the ratio is to limit the scope of the present invention in any aspect It should not be.
한편, 상기 담체로서는 알코올, 오일, 계면활성제, 지방산, 실리콘 오일, 습윤제, 보습제, 점성 변형제, 유제, 안정제, 자외선 차단제, 발색제, 향료 등이 예시될 수 있다. Examples of the carrier include alcohols, oils, surfactants, fatty acids, silicone oils, humectants, moisturizers, viscosifiers, emulsifiers, stabilizers, sunscreens, coloring agents and perfumes.
상기 담체로서 사용될 수 있는 알코올, 오일, 계면활성제, 지방산, 실리콘 오일, 습윤제, 보습제, 점성 변형제, 유제, 안정제, 자외선 차단제, 발색제, 향료 로 사용될 수 있는 화합물/조성물 등은 이미 당업계에 공지되어 있기 때문에 당업자라면 적절한 해당 물질/조성물을 선택하여 사용할 수 있다.
The compounds / compositions which can be used as the carrier and which can be used as alcohols, oils, surfactants, fatty acids, silicone oils, wetting agents, moisturizers, viscosifiers, emulsions, stabilizers, sunscreens, A person skilled in the art can select and use appropriate substances / compositions.
전술한 바와 같이, 본 발명에 따르면 알러지성 질환의 개선제 조성물을 제공할 수 있다. 또한 본 발명에 따르면 염증성 질환의 개선제 조성물을 제공할 수 있다. 본 발명의 알러지성 질환의 개선제 조성물과 염증성 질환의 개선제 조성물은 약품, 기능성 식품, 화장품 등으로 제품화될 수 있다.
As described above, the present invention can provide an agent composition for improving allergic diseases. Also, according to the present invention, an agent composition for improving inflammatory diseases can be provided. The composition for improving allergic diseases and the composition for improving inflammatory diseases of the present invention can be commercialized as medicines, functional foods, cosmetics and the like.
도 1은 밀겨 추출물로부터의 유효물질 분리 과정의 모식도이다.
도 2는 [화학식 1]의 화합물의 ESI-MS 스펙트럼이다.
도 3은 [화학식 1]의 화합물의 1H-NMR 스펙트럼이다.
도 4는 [화학식 1]의 화합물의 13C-NMR 스펙트럼이다.
도 5는 [화학식 2]의 화합물의 ESI-MS 스펙트럼이다.
도 6은 [화학식 2]의 화합물의 1H-NMR 스펙트럼이다.
도 7은 [화학식 2]의 화합물의 13C-NMR 스펙트럼이다.
도 8은 밀겨 추출물로부터 분리한 유효물질의 탈과립 억제 활성을 보여주는 결과이다.
도 9는 밀겨 추출물로부터 분리한 유효물질의 사이토카인 생성 억제 활성을 보여주는 결과이다.
도 10은 밀겨 추출물로부터 분리한 유효물질의 사이토카인 전사 인자인 NF-κB의 발현을 억제함을 보여주는 결과이다.
도 11은 밀겨 추출물로부터 분리한 유효물질의 MAPK 발현 억제 활성 및 p-AKT 발현 억제 활성을 보여주는 결과이다.BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic diagram of a process for separating an effective substance from a pressed extract. FIG.
2 is an ESI-MS spectrum of the compound of formula (1).
3 is a 1 H-NMR spectrum of a compound of formula (1).
4 is a 13 C-NMR spectrum of the compound of formula (1).
5 is an ESI-MS spectrum of the compound of formula (2).
6 is a 1 H-NMR spectrum of the compound of formula (2).
7 is a 13 C-NMR spectrum of the compound of formula (2).
Fig. 8 shows the results of showing the degranulation inhibitory activity of the active substance isolated from the press-extract.
FIG. 9 shows the activity of inhibiting the cytokine production of the active substance isolated from the press extract.
Fig. 10 shows the results of inhibiting the expression of NF-κB, a cytokine transcription factor of the active substance isolated from the press-extract.
FIG. 11 shows the MAPK expression inhibiting activity and the p-AKT expression inhibiting activity of the active substance isolated from the press-extract.
이하 본 발명을 실시예 및 실험예를 참조하여 설명한다. 그러나 본 발명의 범위가 이러한 실시예 및 실험예에 한정되는 것은 아니다.
Hereinafter, the present invention will be described with reference to Examples and Experimental Examples. However, the scope of the present invention is not limited to these examples and experimental examples.
<< 실시예Example > > 밀겨Push 추출물로부터 From the extract 항알러지Anti-allergy 활성을 갖는 유효물질의 분리 및 동정 Isolation and identification of active substances with activity
<< 실시예Example 1> 1> 밀겨Push 추출물로부터의 유효물질의 분리 Isolation of the active substance from the extract
밀(Triticum aestivum L.)의 도정 부산물인 밀겨(wheat bran)에 에탄올을 가하고 24시간 3회 냉침 추출 하였다. 추출액을 여과한 후에 여액을 감압 농축기를 이용하여 에탄올 추출물을 얻었으며, 추출물을 증류수에 현탁시킨 후 n-헥산으로 용매 분획한 후 물층에 대해서 CH2Cl2로 다시 용매 분획하였다. 이들 분획물 중에서 항알러지 활성을 나타낸 헥산 분획물을 감압상태에서 증발시켜 추출물을 얻었고, 실리카겔 크로마토그래피를 헥산:CH2Cl2(5:1, 1:1, 0:1), CH2Cl2:메탄올(80:1, 50:1, 25:1, 10:1, 5:1, 2:1)로 시행하여 10개의 분획(G36H-3-1~10)으로 나누었고, 소분획 G36H-3-10에 대하여 90% 메탄올과 헥산으로 분획하여 분획물 90% 메탄올 추출물 G36H-4-3을 얻었다. 분획 G36H-4-3에 대하여 실리카겔 크로마토그래피를 이동상 헥산:아세톤(1:0, 90:1, 70:1, 50:1, 30:1, 10:1, 5:1, 3:1, 2:1)으로 시행하여 11 개의 분획(G36H-6-1~11)으로 나누었고, 소분획 G36H-6-3으로부터 prep. HPLC(YMC-ODS, 95-100% MeCN, 20ml/min)를 이용하여 화합물 1(G36H-9-4)과 2(G36H-9-5)를 분리하였다.Wheat ( Triticum ethanol was added to wheat bran which is a byproduct of aestivum L., and the mixture was frozen three times for 24 hours. The extract was filtered, and then the ethanol extract was obtained from the filtrate using a vacuum condenser. The extract was suspended in distilled water, followed by solvent fractionation with n-hexane, followed by solvent fractionation with CH 2 Cl 2 . Among these fractions, hexane fraction exhibiting anti-allergic activity was evaporated under reduced pressure to obtain an extract. The silica gel chromatography was carried out with hexane: CH 2 Cl 2 ( 5: 1, 1: 1, 0: 1), CH 2 Cl 2 : (G36H-3-1 to 10), and the fraction G36H-3-10 (50: 1, 50: Was fractionated with 90% methanol and hexane to obtain 90% methanol extract of fraction G36H-4-3. Fraction G36H-4-3 was purified by silica gel chromatography using mobile phase hexane: acetone (1: 0, 90: 1, 70: 1, 50: 1, 30: 1, 10: 1, 5: : 1) and divided into 11 fractions (G36H-6-1 to 11). From the fraction G36H-6-3, Compound 1 (G36H-9-4) and 2 (G36H-9-5) were separated using HPLC (YMC-ODS, 95-100% MeCN, 20 ml / min).
상기 유효물질의 분리 과정의 모식도를 [도 1]에 나타내었다. A schematic view of the separation process of the effective substance is shown in Fig.
<< 실시예Example 2> 2> 유효물질의 동정Identification of active substances
<실시예 2-1> 화합물 1의 동정 ≪ Example 2-1 > Identification of Compound 1
상기 분리한 화합물 1에 대해 물리화학적 및 분광학적 분석을 실시하였다.The separated Compound 1 was subjected to physicochemical and spectroscopic analyzes.
White amorphous powder; ESI-MS (negative mode) m/z 375 [M - H]-, 751 [2M - H]-; 1H-NMR (CDCl3+CD3OD, 500 MHz) δ 6.20 (2H, d, J = 2.5 Hz, H-4, 6), 6.14 (1H, t, J = 2.5 Hz, H-3), 2.46 (2H, t, J = 7.5 Hz, H-1'), 1.56 (2H, m, H-2'), 1.22-1.30 (32H, m, H-3', 4', 5', 6', 7', 8', 9', 10', 11', 12', 13', 14', 15', 16', 17', 18'), 0.88 (3H, t, J = 7.5 Hz, H-19'); 13C-NMR (CDCl3+CD3OD, 125 MHz) δ 157.5 (C-1, 3), 145.7 (C-5), 107.2 (C-4, 6), 99.9 (C-2), 36.0 (C-1'), 31.9 (C-17'), 31.2 (C-2'), 29.4-29.7 (C-3', 4', 5', 6', 7', 8', 9', 10', 11', 12', 13', 14', 15', 16'), 22.7 (C-18'), 14.0 (C-19')White amorphous powder; ESI-MS (negative mode) m / z 375 [M-H] - , 751 [2M-H] - ; 1 H-NMR (CDCl 3 + CD 3 OD, 500 MHz) δ 6.20 (2H, d, J = 2.5 Hz, H-4, 6), 6.14 (1H, t, J = 2.5 Hz, H-3), M, H-3 ', 4', 5 ', 6'), 2.46 (2H, t, J = 7.5 Hz, , 7 ', 8', 9 ', 10', 11 ', 12', 13 ', 14', 15 ', 16', 17 ', 18'), 0.88 (3H, t, J = 7.5 Hz, H -19 '); 13 C-NMR (CDCl 3 + CD 3 OD, 125 MHz)? 157.5 (C-1,3), 145.7 (C-5), 107.2 3 ', 4', 5 ', 6', 7 ', 8', 9 ', 10'), 31.9 (C-17 '), 31.2 ', 11', 12 ', 13', 14 ', 15', 16 '), 22.7 (C-18'), 14.0 (C-19 '
화합물 1은 흰색의 무정형 분말 형태로서 ESI-MS [m/z 375 (M - H)-, 751 (2M - H)-](도 2)로부터 분자량은 376 amu로 확인하였고, 분자식 C25H44O2임을 알 수 있었으며, 불포화도는 4로 나타났다. 1H-NMR 스펙트럼(도 3)에서는 3 개의 aromatic proton [δH 6.20 (2H, d, J = 2.5 Hz, H-4, 6), 6.14 (1H, t, J = 2.5 Hz, H-3)]이 관찰되었으며, alkyl group proton [δH 2.46 (2H, t, J = 7.5 Hz, H-1'), 1.56 (2H, m, H-2'), 1.22-1.30 (32H, m), 0.88 (3H, t, J = 7.5 Hz, H-19')]을 확인하였다. 13C-NMR(도 4)에서는 벤젠고리와 alkyl group에 기인하는 signal 등 총 25개의 carbon signal을 확인하였다. 이상의 분광학적 데이터와 불포화도로부터 화합물 1은 밀로부터 분리 보고된 5-alkylresorcinol 계열 화합물로 추정하였고, 문헌(J. Agric. Food Chem. 2003, 51, 6683-6688; Chem . Pharm . Bull. 1989, 37, 2431-2434; Biosci. Biotech . Biochem . 1997, 61, 480-486)과의 비교 검토로 [화학식 1]의 5-n-nonadecylresorcinol로 구조 결정하였다. Compound 1 as an amorphous powder in the form of a white ESI-MS [m / z 375 (M - H) -, 751 (2M - H) -] molecular weight (Fig. 2) were identified as 376 amu, molecular formula C 25 H 44 O 2 , and the degree of unsaturation was 4. 1 H-NMR spectrum (Fig. 3), the three aromatic proton [δ H 6.20 (2H , d, J = 2.5 Hz, H-4, 6), 6.14 (1H, t, J = 2.5 Hz, H-3) ] was observed, alkyl group proton [δ H 2.46 (2H, t, J = 7.5 Hz, H-1 '), 1.56 (2H, m, H-2'), 1.22-1.30 (32H, m), 0.88 (3H, t, J = 7.5 Hz, H-19 '). In the 13 C-NMR (FIG. 4), a total of 25 carbon signals including a benzene ring and an alkyl group-derived signal were identified. From the above spectroscopic data and the degree of unsaturation, Compound 1 was estimated to be a 5-alkylresorcinol-based compound reported from wheat and reported in J. Agric. Food Chem . 2003, 51 , 6683-6688; Chem . Pharm . Bull . 1989, 37 , 2431-2434; Biosci. Biotech . Biochem . 1997, 61 , 480-486), the structure was determined by 5-n-nonadecylresorcinol of the formula (1).
<실시예 2-2> 화합물 2의 동정 ≪ Example 2-2 > Identification of Compound 2
상기 분리한 화합물 2에 대해 물리화학적 및 분광학적 분석을 실시하였다.The separated Compound 2 was subjected to physicochemical and spectroscopic analyzes.
White amorphous powder; ESI-MS (positive mode) m/z 405 [M + H]+; (negative mode) m/z 403 [M - H]-; 1H-NMR (CDCl3+CD3OD, 500 MHz) δ 6.20 (2H, d, J = 2.5 Hz, H-4, 6), 6.14 (1H, t, J = 2.5 Hz, H-3), 2.46 (2H, t, J = 7.5 Hz, H-1'), 1.56 (2H, m, H-2'), 1.24-1.30 (36H, m, H-3', 4', 5', 6', 7', 8', 9', 10', 11', 12', 13', 14', 15', 16', 17', 18', 19', 20'), 0.88 (3H, t, J = 7.5 Hz, H-21'); 13C-NMR (CDCl3+CD3OD, 125 MHz) δ 157.5 (C-1, 3), 145.6 (C-5), 107.1 (C-4, 6), 99.8 (C-2), 36.0 (C-1'), 31.9 (C-19'), 31.2 (C-2'), 29.3-29.7 (C-3', 4', 5', 6', 7', 8', 9', 10', 11', 12', 13', 14', 15', 16', 17', 18'), 22.7 (C-20'), 14.0 (C-21')White amorphous powder; ESI-MS (positive mode) m / z 405 [M + H] < + >; (negative mode) m / z 403 [M - H] - ; 1 H-NMR (CDCl 3 + CD 3 OD, 500 MHz) δ 6.20 (2H, d, J = 2.5 Hz, H-4, 6), 6.14 (1H, t, J = 2.5 Hz, H-3), M, H-3 ', 4', 5 ', 6'), 2.46 (2H, t, J = 7.5 Hz, H- , 7 ', 8', 9 ', 10', 11 ', 12', 13 ', 14', 15 ', 16', 17 ', 18', 19 ', 20' J = 7.5 Hz, H-21 '); 13 C-NMR (CDCl 3 + CD 3 OD, 125 MHz)? 157.5 (C-1,3), 145.6 (C-5), 107.1 3 ', 4', 5 ', 6', 7 ', 8', 9 ', 10 (C-1'), 31.9 ', 11', 12 ', 13', 14 ', 15', 16 ', 17', 18 '), 22.7 (C-20'), 14.0
화합물 2는 흰색의 무정형 분말 형태로서 ESI-MS [m/z 405 (M + H)+, 403 (M - H)-](도 5)로부터 분자량은 404 amu로 확인하였고, 분자식 C27H48O2임을 알 수 있었으며, 불포화도는 4로 나타났다. 1H-NMR 스펙트럼(도 6)에서는 3 개의 aromatic proton [δH 6.20 (2H, d, J = 2.5 Hz, H-4, 6), 6.14 (1H, t, J = 2.5 Hz, H-3)]이 관찰되었으며, alkyl group proton [δH 2.46 (2H, t, J = 7.5 Hz, H-1'), 1.56 (2H, m, H-2'), 1.24-1.30 (36H, m), 0.88 (3H, t, J = 7.5 Hz, H-21')]을 확인하였다. 13C-NMR(도 7)에서는 벤젠고리와 alkyl group에 기인하는 signal 등 총 27개의 carbon signal을 확인하였다. 또한, 이상의 분광학적 데이터와 불포화도로부터 화합물 2는 밀로부터 분리 보고된 5-alkylresorcinol 계열 화합물로 추정하였고, 문헌(J. Agric . Food Chem. 2003, 51, 6683-6688; Chem . Pharm . Bull. 1989, 37, 2431-2434; Biosci . Biotech . Biochem . 1997, 61, 480-486)과의 비교 검토로 [화학식 2]의 5-n-heneicosylresorcinol로 구조 결정하였다.
Compound 2 as an amorphous powder in the form of a white ESI-MS [m / z 405 (M + H) +, 403 (M - H) -] molecular weight (Fig. 5) was identified as 404 amu, molecular formula C 27 H 48 O 2 , and the degree of unsaturation was 4. 1 H-NMR spectrum (Fig. 6) in the three aromatic proton [δ H 6.20 (2H , d, J = 2.5 Hz, H-4, 6), 6.14 (1H, t, J = 2.5 Hz, H-3) ] was observed, alkyl group proton [δ H 2.46 (2H, t, J = 7.5 Hz, H-1 '), 1.56 (2H, m, H-2'), 1.24-1.30 (36H, m), 0.88 (3H, t, J = 7.5 Hz, H-21 '). 13 C-NMR (FIG. 7) confirmed 27 carbon signals including benzene ring and alkyl group-derived signals. Further, from the above spectroscopic data and the degree of unsaturation, Compound 2 was estimated as a 5-alkylresorcinol-based compound separated and reported from wheat, and J. Agric . Food Chem . 2003, 51 , 6683-6688; Chem . Pharm . Bull . 1989, 37 , 2431-2434; Biosci . Biotech . Biochem . 1997, 61 , 480-486), the structure was determined to be 5-n-heneicosylresorcinol of formula (2).
<< 실험예Experimental Example > > 밀겨Push 추출물로부터 분리한 유효물질의 Of the active substance isolated from the extract 항알러지Anti-allergy 및 항염증 활성 실험 And anti-inflammatory activity experiment
<< 실험예Experimental Example 1> 1> 밀겨Push 추출물로부터 분리한 유효물질의 Of the active substance isolated from the extract 비만세포주Obesity cell line 탈과립Degranulation 억제 활성 실험 - β- Inhibitory activity Experiment - β- HexosaminidaseHexosaminidase assayassay
Rat basophlic leukemia 셀 라인인 RBL-2H3 세포주를 15% FBS, 100 unit/ml의 페니실린과 스트렙토마이신을 포함하는 MEM 배지와 37, 5% CO2 조건에서 24 well plate에 2X105/well로 분주한 후 24시간 배양하였다. RBL-2H3 cell line, Rat basophlic leukemia cell line, was divided into 2 × 10 5 / well in 24 well plate with MEM medium containing 15% FBS, 100 unit / ml penicillin and streptomycin at 37 and 5% CO 2 And cultured for 24 hours.
상등액을 제거 후 25 ng/ml anti-DNP IgE 가 포함된 MEM 배지를 넣고 4시간 배양 후 PIPES buffer 500㎕로 두 번 세척하고 4mM MgCl2, 5.6mM glucose, 0.1% BSA를 포함시킨 PIPES buffer를 180㎕ 넣고 10분 동안 배양하였다. 전 배양 후 시료를 농도별로 20분간 처리 후 50ng/ml DNP-BSA 20분간 반응시켰다. ice 에서 10분 방치하여 반응을 종결시킨 후 상등액을 25㎕ 씩 96 웰 플레이트에 넣고, 1 mM P-니트로페닐-아세틸-β-D-글루코사미니드를 25㎕ 넣은 후 37℃에서 1시간 반응시켰다. stop solution(0.1M NaHCO3, 0.1M Na2CO3)을 넣고 반응을 종결시킨 후 405nm 파장대에서 ELISA 리더로 흡광도를 측정하였다. 양성 대조군으로는 ketotifen을 사용하였다. After removing the supernatant, MEM medium containing 25 ng / ml anti-DNP IgE was added and incubated for 4 hours. The cells were washed twice with 500 μl of PIPES buffer, and the PIPES buffer containing 4 mM MgCl 2 , 5.6 mM glucose and 0.1% And incubated for 10 minutes. After incubation, the samples were treated for 20 minutes at a concentration of 50 ng / ml DNP-BSA for 20 minutes. After the reaction was terminated by ice, the supernatant was added to a 96-well plate in an amount of 25 μl each, and 25 μl of 1 mM P-nitrophenyl-acetyl-β-D-glucosaminyl was added thereto, followed by reaction at 37 ° C. for 1 hour . stop solution (0.1 M NaHCO 3 , 0.1 M Na 2 CO 3 ), and the absorbance was measured with an ELISA reader at a wavelength of 405 nm. Ketotifen was used as a positive control.
결과를 [도 8]에 나타내었는데, [도 8]를 참조하여 보면 상기 분리된 유효물질 모두 농도 의존적으로 탈과립을 억제함을 확인할 수 있다. 여기서 화합물 1의 EC50는 243.71uM로 나타났고, 화합물 2의 EC50는 174.39uM로 나타났다.The results are shown in FIG. 8. Referring to FIG. 8, it can be confirmed that the separated effective substances suppressed degranulation in a concentration-dependent manner. Here, the EC 50 of Compound 1 was found to be 243.71 uM, and the EC 50 of Compound 2 was found to be 174.39 uM.
<< 실험예Experimental Example 2> 2> 사이토카인의 생성 억제 활성 실험 - Experiments to inhibit the production of cytokines - RT-PCRRT-PCR
BL-2H3 세포를 1X106/well로 6 well plate에 배양 후 IgE를 넣고 4시간 반응시킨다. 그 이후 농도별로 시료 처리하고 DNP-BSA를 첨가하여 각각 37℃에서 20분씩 반응시킨다. PBS로 2번 세척 후 Trizol(Invitrogen)을 넣어서 세포를 용해시킨 후 chloroform(Sigma)를 넣고 13,000rpm에서 15분간 원심분리하여 상층액을 얻었다. 상층액과 isopropanol을 섞은 후 반응시켜 RNA를 침전시킨 후 에탄올로 1회 세척하여 RNA를 분리하였다.BL-2H3 cells were cultured in a 6-well plate at 1 × 10 6 cells / well and incubated for 4 hours with IgE. After that, samples are treated by concentration, DNP-BSA is added and reacted at 37 ° C for 20 minutes each. After washing with PBS twice, Trizol (Invitrogen) was added to dissolve the cells. Then, chloroform (Sigma) was added and the supernatant was obtained by centrifugation at 13,000 rpm for 15 minutes. The RNA was separated by washing the supernatant with isopropanol, precipitating the RNA by the reaction, and washing with ethanol once.
추출한 RNA를 이용하여 정량 후 역전사 효소인 SuperscriptⅢ(Invitrogen)를 사용하여 역전사 연쇄중합반응에 의해 cDNA를 합성하였다. PCR 조건은 94℃ 45초, 55℃ 45초, 72℃ 1분 30초를 35 cycle 반응시켜 DNA를 증폭시켰다. 유전자의 발현 억제 효과를 agarose gel 상에서 비교하였다. 사용한 primer는 아래의 [표 1]과 같고 대조군 유전자는 GAPDH를 사용하였다. 양성 대조군으로는 ketotifen을 사용하였다.CDNA was synthesized by reverse transcription polymerase using Superscript III (Invitrogen), a reverse transcriptase enzyme. The PCR conditions were: 35 cycles of 94 ° C for 45 seconds, 55 ° C for 45 seconds, and 72 ° C for 1 minute and 30 seconds. The gene expression inhibitory effect was compared on agarose gel. The primers used were shown in Table 1 below and the control gene was GAPDH. Ketotifen was used as a positive control.
결과를 [도 9]에 나타내었다. [도 9]를 참조하여 보면 상기 분리된 유효물질은 모두 대체로 농도 의존적으로 사이토카인의 생성을 억제함을 알 수 있다.The results are shown in Fig. Referring to FIG. 9, it can be seen that all of the separated active substances suppress cytokine production in a dose-dependent manner.
<< 실험예Experimental Example 3> 3> 사이토카인 생성의 작용 기전 조사Mechanism of cytokine production
<실험예 3-1> NF -κB 발현 억제 활성 실험 - luciferase assay <Experimental Example 3-1> Inhibitory activity of NF- κB expression- luciferase assay
HEK 293T 세포를 5X104/well로 24 well plate에 배양 후 pGL3-basic luciferase expression 벡터(Promega)에 NF-κB 유전자를 삽입하여 얻은 재조합 벡터와 control reporter로서 Renilla luciferase의 cDNA를 가지는 pRL-SV-40 프라스미드(Promega)를 HEK 293T cell에 lipofectamine(Invitrogen)을 사용하여 co-transfection 하였다. 24시간 후 시료를 처리한 후 세포를 lysis시켜 발광효소의 활성화를 luciferase assay system(Promega)으로 측정하였다. 양성 대조군으로는 ketotifen을 사용하였다.HEK 293T cells were 5X10 4 / well in 24 culture after the well plate pGL3-basic luciferase expression vector (Promega) as a reporter control and a recombinant vector formed by inserting the NF-κB gene Renilla pRL-SV-40 plasmid (Promega) carrying the luciferase cDNA was co-transfected into HEK 293T cells using lipofectamine (Invitrogen). After 24 hours, the cells were lysed and luciferase assay system (Promega) was used to measure the luminescence activity. Ketotifen was used as a positive control.
결과를 [도 10]에 나타내었다. 상기 분리된 유효물질은 모두 양성 대조군 이상으로 NF-κB의 발현을 억제함을 보여주고 있다. The results are shown in Fig. All of the above-mentioned isolated active substances inhibit the expression of NF-kB more than the positive control group.
<실험예 3-2> MAPK 및 p- AKT 생성 억제 활성 실험 - western blot <Experimental Example 3-2> Inhibitory activity of MAPK and p- AKT formation - western blot
IgE와 그것의 항원으로 활성되고 시료가 처리된 상기 <실험예 2>의 RBL-2H3 세포를 PBS로 세척 후 lysis buffer(50mM Tris-HCl, pH 8.0 with 150mM sodium chloride, 1% NP40, 0.5% sodium deoxycholate, 0.1% sodium dodecyl s㎕fate)에 용해시켰다. 13,000rpm으로 20분간 원심 분리하여 단백질을 추출하여 정량하였다. 정량된 단백질을 SDS-PAGE(sodium dodecyl s㎕fate polyacrylamide gel electrophoresis) 를 이용하여 전기 영동 후 polyvinylidene difluoride membrane으로 이동시켰다. membrane은 0.1% Tween 20과 5% 탈지 건조된 우유를 포함하고 있는 phosphate buffered saline으로 blocking 하였다. membrane은 0.1% Tween 20과 5% 탈지 건조된 우유를 포함하고 있는 phosphate buffered saline으로 blocking 하였다. membrane의 단백질은 1차 항체(1:1000)(Cell signaling) 와 horseradish peroxidase와 복합된 2차 항체(1:10000)(SantaCruz)에 반응시킨 후 ECL western detection 시약(Thermo scientific)으로 MAPK(ERK, JNK 및 p38) 및 p-AKT의 발현 정도를 β-actin의 발현 정도와 비교하여 평가하였다.RBL-2H3 cells of the above Experimental Example 2 in which IgE and its antigen were activated and treated were washed with PBS and then lysed in 50 mM Tris-HCl, pH 8.0 with 150 mM sodium chloride, 1% NP40, 0.5% sodium deoxycholate, 0.1% sodium dodecyl sulphate). Proteins were extracted by centrifugation at 13,000 rpm for 20 minutes and quantified. The quantified protein was electrophoresed using SDS-PAGE (sodium dodecyl sulphate polyacrylamide gel electrophoresis) and then transferred to polyvinylidene difluoride membrane. Membranes were blocked with phosphate buffered saline containing 0.1% Tween 20 and 5% skim milk. Membranes were blocked with phosphate buffered saline containing 0.1% Tween 20 and 5% skim milk. Membrane protein was reacted with primary antibody (1: 1000) (Cell signaling) and secondary antibody (1: 10000) (SantaCruz) complexed with horseradish peroxidase and ECK Western blotting reagent (Thermo scientific) JNK and p38) and p-AKT expression levels were compared with those of β-actin.
결과를 [도 11]에 나타내었는데, 상기 분리된 유효물질은 모두 농도 의존적으로 MAPK 및 p-AKT의 발현을 억제함을 알 수 있으며, 처리 농도(300uM)가 같을 경우 양성대조군(Ketotifen)과 유사한 정도의 활성을 보임을 알 수 있다.The results are shown in FIG. 11, which shows that all of the separated active substances inhibit the expression of MAPK and p-AKT in a concentration-dependent manner, and when the treatment concentration (300 μM) is the same, they are similar to the positive control (Ketotifen) , Respectively.
<< 실험예Experimental Example 4> 4> 리폭시게나제Lipoxygenase 활성 억제 실험 Activity inhibition experiment
0.1 M 트리스 완충용액(Tris buffer, pH 8.5) 2 ㎖에 각각의 농도별로 시료 20 ㎕를 첨가하고, 기질인 linoleic acid(최종농도 110 uM) 20 ㎕를 혼합하고 실온에서 5분간 전 반응시켰다. 반응액에 soybean lipoxygenase(Type , 500 UNIT/ 최종농도) 20 ㎕를 첨가한 후 5분간 반응시키고 234 nm에서 흡광도를 측정하였다.20 μl of each sample was added to 2 ml of 0.1 M Tris buffer (pH 8.5), and 20 μl of substrate linoleic acid (final concentration 110 μM) was mixed and reacted for 5 minutes at room temperature. 20 μl of soybean lipoxygenase (Type, 500 UNIT / final concentration) was added to the reaction solution, followed by reaction for 5 minutes and absorbance was measured at 234 nm.
양성대조군으로 페놀계 식품 항산화제인 NDGA(nordihydroguaiaretic acid)를 사용하였고, 각각의 시료에 대한 IC50 값을 구해 평가하였다.NDGA (nordihydroguaiaretic acid), a phenolic food antioxidant, was used as a positive control, and the IC 50 value of each sample was evaluated.
결과를 [표 2]에 나타내었다.The results are shown in Table 2.
<110> LEE, HAI-SOO <120> Composition for Improving Allergy Disease Using the Effective Compound Which Cay Be Isolated from an Extract of Wheat Bran <130> PP10-000 <160> 12 <170> KopatentIn 2.0 <210> 1 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 1 tgtatgctac catctggctt cgg 23 <210> 2 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 2 gtttggaaca gtcgctcgtc atc 23 <210> 3 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 3 caccacgctc ttctgtctac tgaa 24 <210> 4 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 4 ccggactccg tgatgtctaa gtact 25 <210> 5 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 5 accttgcttc accctgttc 19 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 6 ttgtgagcgt ggactcattc 20 <210> 7 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 7 gcccttcagg aacagctatg a 21 <210> 8 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 8 tgtcaacaac atcagtccca aga 23 <210> 9 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 9 tagaagtgat gccccagg 18 <210> 10 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 10 tcatcctcca cctgctccac tgc 23 <210> 11 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 11 gagtcaacgg atttggtcgt 20 <210> 12 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 12 gacaagcttc ccgttctcag 20 <110> LEE, HAI-SOO <120> Composition for Improving Allergy Disease Using the Effective Compound Which Cay Be Isolated from an Extract of Wheat Bran <130> PP10-000 <160> 12 <170> Kopatentin 2.0 <210> 1 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 1 tgtatgctac catctggctt cgg 23 <210> 2 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 2 gtttggaaca gtcgctcgtc atc 23 <210> 3 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 3 caccacgctc ttctgtctac tgaa 24 <210> 4 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 4 ccggactccg tgatgtctaa gtact 25 <210> 5 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 5 accttgcttc accctgttc 19 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 6 ttgtgagcgt ggactcattc 20 <210> 7 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 7 gcccttcagg aacagctatg a 21 <210> 8 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 8 tgtcaacaac atcagtccca aga 23 <210> 9 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 9 tagaagtgat gccccagg 18 <210> 10 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 10 tcatcctcca cctgctccac tgc 23 <210> 11 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 11 gagtcaacgg atttggtcgt 20 <210> 12 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 12 gacaagcttc ccgttctcag 20
Claims (10)
5-n-nonadecylresorcinol or 5-n-henecyl silezocinol as an active ingredient. The composition for improving allergic diseases according to claim 1, wherein the composition comprises 5-n-nonadecylresorcinol.
상기 조성물은 약제학적 조성물인 것을 특징으로 하는 알러지성 질환 개선제 조성물.
The method according to claim 1,
Wherein the composition is a pharmaceutical composition.
상기 조성물은 식품 조성물인 것을 특징으로 하는 알러지성 질환 개선제 조성물.
The method according to claim 1,
Wherein the composition is a food composition.
상기 조성물은 화장품 조성물인 것을 특징으로 하는 알러지성 질환 개선제 조성물.
The method according to claim 1,
Wherein the composition is a cosmetic composition.
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