KR20220136638A - Composition for preventing or treating psoriasis comprising extract of sargassum horneri - Google Patents
Composition for preventing or treating psoriasis comprising extract of sargassum horneri Download PDFInfo
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- KR20220136638A KR20220136638A KR1020210042519A KR20210042519A KR20220136638A KR 20220136638 A KR20220136638 A KR 20220136638A KR 1020210042519 A KR1020210042519 A KR 1020210042519A KR 20210042519 A KR20210042519 A KR 20210042519A KR 20220136638 A KR20220136638 A KR 20220136638A
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Abstract
Description
본 발명은 괭생이모자반(Sargassum horneri) 추출물을 유효성분으로 함유하는 건선 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing or treating psoriasis containing an extract of Sargassum horneri as an active ingredient.
건선(psoriasis)은 피부에 경계가 뚜렷하며 다양한 크기의 은백색의 비늘로 덮여 있는 홍반성 구진 및 판이 형성되는 질환으로, 악화와 호전이 반복되는 만성 염증성 피부 질환이다. 이의 조직학적인 특징은 상피의 과다 증식이며, 이 외에도 고름, 인설, 발진 등 다양한 임상 양상을 보인다.Psoriasis is a chronic inflammatory skin disease characterized by the formation of erythematous papules and plaques covered with silver-white scales of various sizes with clear boundaries on the skin. Its histological characteristics are hyperplasia of the epithelium, and in addition, it shows various clinical features such as pus, scales, and rash.
건선의 원인은 아직 명확하게 알려지지 않았지만, 원인으로 추측되는 요소로는 유전적 요인, 환경적 악화 혹은 유발 요인, 면역학적 요인 등이 있다. 현재는 유전적 요인을 기반으로 하여 개인의 생활, 환경적 요인이 유발 인자로 작용하고, 면역학적 요인에 의해 각질 형성 세포의 증식 및 염증 반응이 일어나는 것으로 알려져 있다. 건선의 악화 또는 유발 요인으로는 피부 외상, 감염, 겨울과 같은 차고 건조한 기후, 건조한 피부, 스트레스, 약물 등이 있다.The cause of psoriasis is still not clearly known, but factors that are presumed to be the cause include genetic factors, environmental deterioration or trigger factors, and immunological factors. It is currently known that, based on genetic factors, personal life and environmental factors act as trigger factors, and proliferation and inflammatory response of keratinocytes occur by immunological factors. Exacerbating or triggering factors for psoriasis include skin trauma, infection, cold, dry climates such as winter, dry skin, stress, and medications.
건선의 치료 방법은 질환 부위에 약물을 바르거나, 자외선을 이용한 광선 치료 방법이 있다. 상기 약물로 부신피질호르몬제, 비타민 D 유도체, 보습제를 비롯하여, 비타민 A 합성 유도체, 면역억제제인 사이클로스포린(cyclosporine), 메토트렉세이트(methotrexate), 스테로이드(steroid) 등의 약물 등을 사용하나, 강력한 부신피질호르몬제를 너무 오래 바르면 모세혈관 확장, 팽창 선조, 피부 위축 등 여러 가지 부작용이 나타날 수 있고, 사이클로스포린은 신장 기능 손상과 혈압에 문제를 일으킬 수 있으며, 메토트렉세이트는 누적하여 사용하면 간경변이나 섬유증을 일으킬 수 있는 문제점이 있다. The treatment of psoriasis includes applying a drug to the diseased area or phototherapy using ultraviolet rays. As the above drugs, drugs such as corticosteroids, vitamin D derivatives, moisturizers, vitamin A synthetic derivatives, immunosuppressants cyclosporine, methotrexate, steroids, etc. are used, but strong corticosteroids If the agent is applied for too long, various side effects such as capillary dilatation, dilated striatum, and skin atrophy may appear. Cyclosporine may cause damage to kidney function and problems with blood pressure. Methotrexate may cause cirrhosis or fibrosis if used accumulated There is a problem.
괭생이모자반(Sargassum horneri)은 우리나라 해안에 널리 분포하고 있는 갈조식물 모자반목 모자반과의 황갈색 해조로, 길이는 3~5m 정도이다. 헛뿌리는 쟁반 모양이며 중심에서 원기둥 모양의 줄기가 나오고 곁가지를 치고, 줄기의 가운데와 윗부분은 원기둥 모양이며 미끈하지만 밑 부분과 가지에는 가시가 있다. 잎은 긴 타원 모양이거나 줄 모양이며 가장자리가 깃꼴로 갈라진다. 점심대(upper sublittoral belt) 윗부분의 바위 위에서 자라고 썰물 때 몸의 끝부분이 물 위에 떠다니며, 주로 사료로 쓰거나 식용으로 사용되지만, 건선 질환의 개선을 위한 기능성 소재로서 괭생이모자반에 대한 연구는 현재까지 보고된 바 없다. Sargassum horneri is a yellowish-brown seaweed of the brown algae plant of the algae family, which is widely distributed along the coast of Korea, and has a length of about 3 to 5 m. Heotroot is in the shape of a tray, and a cylindrical stem emerges from the center and forms side branches. The leaves are long oval or line-shaped, and the edges are pinnately divided. It grows on the rocks above the upper sublittoral belt, and the tip of its body floats on the water at low tide, and is mainly used as feed or food. has not been reported
본 발명의 목적은 부작용이 적고 항건선 효능이 우수한 천연물의 추출물을 이용한 건선 치료제를 제공하는 데에 있다.An object of the present invention is to provide a therapeutic agent for psoriasis using an extract of a natural product having few side effects and excellent anti-psoriasis efficacy.
상기의 목적을 달성하기 위하여, 본 발명은 괭생이모자반(Sargassum horneri) 추출물을 유효성분으로 함유하는 건선 예방 또는 치료용 약학 조성물을 제공한다.In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating psoriasis containing an extract of Sargassum horneri as an active ingredient.
본 발명은 괭생이모자반(Sargassum horneri) 추출물을 유효성분으로 함유하는 건선 예방 또는 개선용 피부 외용제 조성물을 제공한다.The present invention provides a composition for external application for skin for preventing or improving psoriasis containing an extract of Sargassum horneri as an active ingredient.
또한, 본 발명은 괭생이모자반(Sargassum horneri) 추출물을 유효성분으로 함유하는 건선 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving psoriasis containing an extract of Sargassum horneri as an active ingredient.
본 발명에 따른 괭생이모자반 추출물은 건선 관련 병인 인자들을 억제하여 우수한 항염 활성을 나타내고, 건선에 따른 피부 홍반, 피부 각질 및 표피 조직 두께 증가와 같은 증상들을 억제하는 항건선 활성을 가지는 바, 건선 예방, 치료 또는 개선을 위한 약학 조성물, 피부 외용제 조성물 및 건강기능식품 조성물로 활용할 수 있다.The extract according to the present invention exhibits excellent anti-inflammatory activity by inhibiting psoriasis-related etiological factors, and has anti-psoriatic activity to suppress symptoms such as skin erythema, keratin and increase in epidermal tissue thickness due to psoriasis, preventing psoriasis , it can be used as a pharmaceutical composition for treatment or improvement, a composition for external application to the skin, and a health functional food composition.
또한, 본 발명은 천연물을 이용함으로써 부작용이 적고 보다 안전하게 건선을 예방, 치료 또는 개선할 수 있다.In addition, the present invention can prevent, treat or improve psoriasis more safely with fewer side effects by using a natural product.
도 1은 본 발명의 일 실험예에 따른 괭생이모자반 추출물의 건선 관련 병인인자(IL-6, IL-8, TNF-α) 생성 억제 효능을 확인한 것이다.
도 2는 본 발명의 다른 실험예에 따른 괭생이모자반 추출물의 항건선 효능과 관련된 신호기전을 확인한 것이다.
도 3은 본 발명의 다른 실험예에 따른 건선 마우스 모델에서 괭생이모자반 추출물 처리에 따른 임상적 변화를 확인한 것이다.
도 4는 본 발명의 다른 실험예에 따른 건선 마우스 모델에서 괭생이모자반 추출물 처리에 따른 피부 조직학적 변화를 확인한 것이다.1 is a confirmation of the psoriasis-related etiological factors (IL-6, IL-8, TNF-α) production inhibitory efficacy of the extract according to an experimental example of the present invention.
Figure 2 is a confirmation of the signaling mechanism related to the anti-psoriasis efficacy of the extract according to another experimental example of the present invention.
Figure 3 confirms the clinical change according to the treatment of hoesaengi hat extract in a mouse model of psoriasis according to another experimental example of the present invention.
Figure 4 confirms the histological changes of the skin according to the treatment of the hoesaengi hat extract in a mouse model of psoriasis according to another experimental example of the present invention.
이하, 본 발명을 상세하게 설명하기로 한다.Hereinafter, the present invention will be described in detail.
본 발명자는 여러 해양수산생물자원 유래 추출물로 항건선 효능에 대해 연구하던 중, 괭생이모자반 추출물에서 우수한 항건선 활성, 이의 신호기전 및 건선 마우스 모델에서의 임상적 변화 등을 확인함으로써, 본 발명을 완성하였다.While the present inventor was studying the anti-psoriasis efficacy with extracts derived from various marine aquatic biological resources, the present invention completed.
본 발명은 괭생이모자반(Sargassum horneri) 추출물을 유효성분으로 함유하는 건선 예방 또는 치료용 약학 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating psoriasis containing an extract of Sargassum horneri as an active ingredient.
본 명세서에서, "괭생이모자반(Sargassum horneri)"이란, 상술한 바와 같이, 우리나라 해안에 널리 분포하고 있는 갈조식물 모자반목 모자반과의 황갈색 해조로, 사료나 식용으로 사용되고 있다.In the present specification, " Sargassum horneri " is, as described above, a yellowish-brown seaweed of the brown algae plant Mojabanum mojaban family that is widely distributed in the coast of Korea, and is used as feed or food.
본 명세서에서, "추출물"이란, 추출 방법, 추출 용매, 추출된 성분 또는 추출물의 형태를 불문하고 천연물의 성분을 뽑아냄으로써 얻어진 물질을 의미하는 것으로, 천연물의 성분을 뽑아내어 얻어진 물질을 추출 후 다른 방법으로 가공 또는 처리하여 얻어질 수 있는 물질을 모두 포함할 수 있다.As used herein, the term "extract" refers to a substance obtained by extracting a component of a natural product regardless of an extraction method, an extraction solvent, an extracted component, or the form of an extract. It may include any material obtainable by processing or processing by the method.
상기 추출물은 당해 기술 분야에서 통상적으로 사용하는 방법에 따라 추출될 수 있고, 예를 들어, 열수 추출, 초음파 추출법, 여과법, 환류 추출법 등이 있으며, 이들은 단독으로 수행되거나 2종 이상의 방법을 병용하여 수행될 수 있다.The extract may be extracted according to a method commonly used in the art, for example, hot water extraction, ultrasonic extraction, filtration, reflux extraction, etc., which are performed alone or in combination of two or more methods. can be
본 발명에 있어서, 상기 괭생이모자반 추출물은 상기 괭생이모자반의 뿌리, 줄기, 잎, 전초 또는 이들의 혼합물을 물, C1 내지 C4의 알코올 또는 이의 혼합물을 용매로 하여 추출한 것일 수 있고, 예를 들어, 메탄올, 에탄올, 프로판올, 부탄올 또는 이의 수용액 등을 상기 용매로 포함할 수 있으며, 바람직하게는 60 내지 80 중량%, 보다 바람직하게는 70 중량% 에탄올 수용액일 수 있으나, 이에 제한되는 것은 아니다.In the present invention, the hoesaengnijaban extract may be obtained by extracting the roots, stems, leaves, outposts, or mixtures thereof of the hoesaengnijaban using water, C1 to C4 alcohol or a mixture thereof as a solvent, for example, , methanol, ethanol, propanol, butanol, or an aqueous solution thereof, etc. may be included as the solvent, preferably 60 to 80% by weight, more preferably 70% by weight of an aqueous ethanol solution, but is not limited thereto.
본 발명에 있어서, 상기 괭생이모자반 추출물은 피부각질세포(keratinocytes)의 염증 반응을 억제할 수 있다.In the present invention, the hoesaengi hat extract can suppress the inflammatory response of the skin keratinocytes (keratinocytes).
보다 상세하게는, 상기 괭생이모자반 추출물은 IL-6(interleukin 6), IL-8(interleukin 8), 및 TNF-α(tumor necrosis factor-α)로 이루어진 군에서 선택되는 하나 이상의 건선 관련 병인인자의 생성을 억제하여, 항건선 효능을 나타낼 수 있다.More specifically, the extract is one or more psoriasis-related etiological factors selected from the group consisting of IL-6 (interleukin 6), IL-8 (interleukin 8), and TNF-α (tumor necrosis factor-α). By inhibiting the production of , it can exhibit anti-psoriasis efficacy.
상기 괭생이모자반 추출물은 단백질 키나아제 B(protein kinase B, PKB)로도 알려진 AKT 및 NF-κB(nuclear factor kappa-light-chain-enhancer of activated B cells) 신호 기전을 통해 상기의 항건선 효능을 조절할 수 있다.The extract can regulate the anti-psoriasis efficacy through the signaling mechanism of AKT and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), also known as protein kinase B (PKB). have.
본 발명의 일 실험예에 따르면, hTNF-α/IFN-γ로 건선이 유발된 피부각질세포에 괭생이모자반 추출물을 처리한 결과, 증가된 IL-6, IL-8, 및 TNF-α의 생성이 감소하였고, p-AKT 및 NF-κB의 발현이 억제됨을 확인할 수 있었다.According to an experimental example of the present invention, as a result of treatment of psoriasis-induced skin keratinocytes with hTNF-α/IFN-γ extract, increased production of IL-6, IL-8, and TNF-α was decreased, and it was confirmed that the expression of p-AKT and NF-κB was suppressed.
또한, 상기 괭생이모자반 추출물은 피부 홍반(erythema), 피부 각질(scaling) 및 표피 조직 두께 증가로 이루어진 군에서 선택되는 하나 이상의 건선 유사 병변의 증상을 억제할 수 있다.In addition, the hoesaengi hat extract can suppress the symptoms of one or more psoriasis-like lesions selected from the group consisting of skin erythema, skin scaling, and increased epidermal tissue thickness.
본 발명의 일 실험예에 따르면, 이미퀴모드(Imiquimod, IMQ)로 건선이 유발된 마우스 모델에 상기 추출물을 처리한 경우, 건선 유사 병변 증상들이 감소하는 것을 확인할 수 있었다.According to an experimental example of the present invention, when the extract was treated in a mouse model induced with psoriasis with Imiquimod (IMQ), it was confirmed that the symptoms of psoriasis-like lesions were reduced.
본 발명에 있어서, 상기 건선은 물방울 건선, 판상 건선, 홍피성 건선, 농포성 건선, 박탈성 건선 등을 포함할 수 있으나, 이에 제한되는 것은 아니다.In the present invention, the psoriasis may include, but is not limited to, waterdrop psoriasis, plaque psoriasis, erythrodermic psoriasis, pustular psoriasis, exfoliative psoriasis, and the like.
본 명세서에서, "예방"이란, 본 발명에 따른 조성물의 투여에 의해 건선 또는 상기 질환의 적어도 하나 이상의 증상의 발생을 억제시키거나 발병을 지연시키는 모든 행위를 의미한다. 또한, 재발을 예방하거나 방지하기 위해 상기 질병에 차도가 있는 대상의 치료를 포함할 수 있다. As used herein, "prevention" refers to any action that suppresses or delays the onset of psoriasis or at least one or more symptoms of the disease by administration of the composition according to the present invention. It may also include treating a subject in remission of the disease to prevent or prevent recurrence.
본 명세서에서, "치료"란, 본 발명에 따른 조성물의 투여에 의해 건선 또는 상기 질환의 적어도 하나 이상의 증상을 완화, 감소 또는 소멸시키는 등 그 증세를 호전시키거나 이롭게 변경하는 모든 행위를 의미한다.As used herein, "treatment" refers to any action that improves or advantageously changes the symptoms, such as alleviating, reducing, or eliminating at least one symptom of psoriasis or the disease by administering the composition according to the present invention.
본 명세서에서, "약학 조성물"이란, 특정한 목적을 위해 투여되는 조성물로, 본 발명의 목적상 건선 또는 상기 질환의 적어도 하나 이상의 증상을 예방, 치료 또는 재발을 방지하기 위해 투여되는 것을 의미한다.As used herein, the term "pharmaceutical composition" refers to a composition administered for a specific purpose, and for the purpose of the present invention, is administered to prevent, treat, or prevent recurrence of at least one symptom of psoriasis or the disease.
본 발명에 따른 약학 조성물은 약학적 분야의 통상적인 방법에 따라 제조될 수 있다. 상기 약학 조성물은 제형에 따라 약학적으로 허용가능한 적절한 담체와 배합될 수 있고, 필요에 따라, 부형제, 희석제, 분산제, 유화제, 완충제, 안정제, 결합제, 붕해제, 용제 등을 더 포함하여 제조될 수 있다. 상기 적절한 담체 등은 본 발명에 따른 괭생이모자반 추출물의 활성 및 특성을 저해하지 않는 것으로, 투여 형태 및 제형에 따라 달리 선택될 수 있다.The pharmaceutical composition according to the present invention may be prepared according to a conventional method in the pharmaceutical field. The pharmaceutical composition may be combined with an appropriate pharmaceutically acceptable carrier according to the formulation, and if necessary, excipients, diluents, dispersants, emulsifiers, buffers, stabilizers, binders, disintegrants, solvents, etc. may be prepared have. The appropriate carrier and the like do not inhibit the activity and properties of the extract according to the present invention, and may be selected differently depending on the dosage form and formulation.
본 발명에 따른 약학 조성물은 어떠한 제형으로도 적용될 수 있고, 보다 상세하게는 통상의 방법에 따라 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 비경구형 제형으로 제형화하여 사용될 수 있다.The pharmaceutical composition according to the present invention can be applied in any dosage form, and more specifically, it can be used by formulating oral dosage forms, external preparations, suppositories, and parenteral dosage forms of sterile injection solutions according to conventional methods.
상기 경구형 제형 중 고형 제형은 정제, 환제, 산제, 과립제, 겔제, 캡슐제 등의 형태로, 적어도 하나 이상의 부형제, 예를 들면, 전분, 칼슘카보네이트, 수크로스, 락토오스, 솔비톨, 만니톨, 셀룰로오스, 젤라틴 등을 섞어 조제할 수 있고, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 포함될 수 있다. 또한, 캡술제형의 경우 상기 언급한 물질 외에도 지방유와 같은 액체 담체를 더 포함할 수 있다.The solid dosage form among the oral dosage forms is in the form of tablets, pills, powders, granules, gels, capsules, etc., and at least one or more excipients, for example, starch, calcium carbonate, sucrose, lactose, sorbitol, mannitol, cellulose, It can be prepared by mixing gelatin, etc., and lubricants such as magnesium stearate and talc in addition to simple excipients may be included. In addition, the capsule formulation may further include a liquid carrier such as fatty oil in addition to the above-mentioned substances.
상기 경구형 제형 중 액상 제형은 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.Among the oral dosage forms, liquid formulations include suspensions, solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients, for example, wetting agents, sweeteners, fragrances, preservatives, etc. may be included. have.
상기 비경구 제형은 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함될 수 있다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. 이에 제한되지 않고, 당해 기술 분야에 알려진 적합한 제제를 모두 사용 가능하다.The parenteral formulation may include a sterile aqueous solution, a non-aqueous solution, a suspension, an emulsion, a freeze-dried formulation, and a suppository. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As the base of the suppository, witepsol, macrogol, Tween 61, cacao butter, laurin fat, glycerogelatin, and the like can be used. Without being limited thereto, any suitable agent known in the art may be used.
또한, 본 발명에 따른 약학 조성물은 치료 효능의 증진을 위해 칼슘이나 비타민 등을 더 첨가할 수 있다. In addition, the pharmaceutical composition according to the present invention may further add calcium or vitamins to enhance therapeutic efficacy.
본 발명에 따른 약학 조성물에 있어서, 상기 약학 조성물은 약학적으로 유효한 양으로 투여될 수 있다. In the pharmaceutical composition according to the present invention, the pharmaceutical composition may be administered in a pharmaceutically effective amount.
본 명세서에서, "약학적으로 유효한 양"이란, 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분하며 부작용을 일으키지 않을 정도의 양을 의미한다.As used herein, the term "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment and not to cause side effects.
상기 약학 조성물의 유효 용량 수준은 사용 목적, 환자의 연령, 성별, 체중 및 건강 상태, 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 방법, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 배합 또는 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 달리 결정될 수 있다. 예를 들어, 일정하지는 않지만 일반적으로 0.001 내지 100mg/kg으로, 바람직하게는 0.01 내지 10mg/kg을 일일 1회 내지 수회 투여될 수 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The effective dose level of the pharmaceutical composition may be determined according to the purpose of use, the age, sex, weight and health status of the patient, the type of disease, severity, drug activity, sensitivity to drug, administration method, administration time, administration route and excretion rate, treatment It may be determined differently depending on factors including the duration, formulation, or concurrently used drugs, and other factors well known in the medical field. For example, although not constant, generally 0.001 to 100 mg/kg, preferably 0.01 to 10 mg/kg, may be administered once to several times a day. The above dosage does not limit the scope of the present invention in any way.
본 발명에 따른 약학 조성물은 건선이 발생할 수 있는 임의의 동물에 투여할 수 있고, 상기 동물은 예를 들어, 인간 및 영장류뿐만 아니라 소, 돼지, 말, 개 등의 가축 등을 포함할 수 있다.The pharmaceutical composition according to the present invention may be administered to any animal capable of developing psoriasis, and the animal may include, for example, not only humans and primates, but also livestock such as cattle, pigs, horses, and dogs.
본 발명에 따른 약학 조성물은 제제 형태에 따른 적당한 투여 경로로 투여될 수 있고, 목적 조직에 도달할 수 있는 한 경구 또는 비경구의 다양한 경로를 통하여 투여될 수 있다. 투여 방법은 특히 한정할 필요 없이, 예를 들면, 경구, 직장 또는 정맥, 근육, 피부 도포, 호흡기내 흡입, 자궁내 경막 또는 뇌혈관내(intracere-broventricular) 주사 등의 통상적인 방법으로 투여될 수 있다.The pharmaceutical composition according to the present invention may be administered by an appropriate administration route according to the form of the formulation, and may be administered through various routes, either oral or parenteral, as long as it can reach the target tissue. The administration method is not particularly limited, and for example, oral, rectal or intravenous, muscle, skin application, respiratory inhalation, intrauterine dural or intracerebroventricular injection, etc. may be administered in a conventional manner. have.
본 발명에 따른 약학 조성물은 건선의 예방 또는 치료를 위하여 단독으로 사용될 수 있고, 수술 또는 다른 약물 치료 등과 병용하여 사용될 수 있다.The pharmaceutical composition according to the present invention may be used alone for the prevention or treatment of psoriasis, or may be used in combination with surgery or other drug treatment.
본 발명은 괭생이모자반(Sargassum horneri) 추출물을 유효성분으로 함유하는 건선 예방 또는 개선용 피부 외용제 조성물을 제공한다.The present invention provides a composition for external application for skin for preventing or improving psoriasis containing an extract of Sargassum horneri as an active ingredient.
본 명세서에서, "개선"이란, 본 발명에 따른 조성물에 의해 건선, 또는 상기 질환의 적어도 하나 이상의 증상이 완화, 감소, 또는 소멸시키는 등 그 증세를 호전시키거나 이롭게 변경하는 모든 행위를 의미한다.As used herein, "improvement" refers to any action that improves or advantageously changes the symptoms of psoriasis or at least one or more symptoms of the disease by the composition according to the present invention, such as alleviation, reduction, or disappearance.
상기 괭생이모자반 추출물은 우수한 항건선 효능을 가지는 바, 건선 예방 또는 개선을 위한 피부 외용제 조성물로 활용할 수 있다.The hoesaengnimojaban extract has an excellent anti-psoriasis effect, and can be used as an external composition for skin for preventing or improving psoriasis.
이에 상응하는 특징들은 상술된 부분에서 대신할 수 있다.Corresponding features may be substituted for the above-mentioned parts.
본 발명에 따른 피부 외용제 조성물은 화장품학 또는 피부과학적으로 허용 가능한 매질 또는 기제를 함유하여 제형화될 수 있다. 이는 국소적용에 적합한 모든 제형으로서, 예를 들면, 용액, 수성액, 겔, 고체, 반죽 무수 생성물, 페이스트, 수상에 유상을 분산시켜 얻은 에멀젼, 현탁액, 마이크로에멀젼, 마이크로캡슐, 미세과립구 또는, 이온형(리포좀) 및 비이온형의 소낭 분산제의 형태로, 또는 크림, 스킨, 로션, 파우더, 연고, 스프레이, 팩, 도말제, 패치, 또는 콘실 스틱의 형태로 제공될 수 있다. 포말(foam)의 형태로 또는 압축된 추진제를 더 함유한 에어로졸 조성물의 형태로도 사용될 수 있다. 이들 조성물은 당해 분야의 통상적인 방법에 따라 제조될 수 있다.The composition for external application for skin according to the present invention may be formulated containing a cosmetically or dermatologically acceptable medium or base. These are all formulations suitable for topical application, for example, solutions, aqueous liquids, gels, solids, kneaded dry products, pastes, emulsions obtained by dispersing the oil phase in an aqueous phase, suspensions, microemulsions, microcapsules, microgranules or ions. It may be provided in the form of vesicular dispersions in the form of (liposome) and nonionic forms, or in the form of creams, skins, lotions, powders, ointments, sprays, packs, smears, patches, or cone sticks. It can also be used in the form of a foam or in the form of an aerosol composition further containing a compressed propellant. These compositions can be prepared according to conventional methods in the art.
상기 피부 외용제 조성물은 지방 물질, 유기용매, 용해제, 농축제, 겔화제, 연화제, 항산화제, 현탁화제, 안정화제, 발포제(foaming agent), 방향제, 계면활성제, 물, 이온형 또는 비이온형 유화제, 충전제, 금속이온봉쇄제, 킬레이트화제, 보존제, 비타민, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 또는 친유성 활성제, 지질 소낭 또는 화장품에 통상적으로 사용되는 임의의 다른 성분과 같은 화장품학 또는 피부과학 분야에서 통상적으로 사용되는 보조제를 함유할 수 있다. 상기 보조제는 화장품학 또는 피부과학 분야에서 일반적으로 사용되는 양으로 도입될 수 있다.The composition for external application for skin includes a fatty substance, an organic solvent, a solubilizer, a thickener, a gelling agent, an emollient, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, a surfactant, water, an ionic or non-ionic emulsifier cosmetology, such as fillers, sequestering agents, chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic actives, lipid vesicles or any other ingredient commonly used in cosmetics; It may contain adjuvants commonly used in the field of dermatology. The adjuvant may be introduced in an amount generally used in the field of cosmetics or dermatology.
또한, 본 발명은 괭생이모자반(Sargassum horneri) 추출물을 유효성분으로 함유하는 건선 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving psoriasis containing an extract of Sargassum horneri as an active ingredient.
상기 괭생이모자반 추출물은 우수한 항건선 효능을 가지는 바, 건선 예방 또는 개선을 위한 건강기능식품 조성물로 활용할 수 있다.The hoesaengimojaban extract has excellent anti-psoriasis efficacy, and can be used as a health functional food composition for preventing or improving psoriasis.
이에 상응하는 특징들은 상술된 부분에서 대신할 수 있다.Corresponding features may be substituted for the above-mentioned parts.
본 명세서에서, "건강기능식품"이란, 건강기능식품에 관한 법률 제6727호에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 포함하며, 영양 공급 외에도 본 발명의 목적상 건선의 예방, 생체 방어, 면역, 회복 등의 생체 조절 기능이 효율적으로 나타나도록 가공된 의학, 의료 효과가 높은 식품을 의미한다.As used herein, the term "health functional food" includes food manufactured and processed using raw materials or ingredients useful for the human body in accordance with Act No. 6727 of the Health Functional Food Act, and in addition to nutritional supply, the purpose of the present invention It refers to foods with high medical and medical effects that are processed to efficiently exhibit bioregulatory functions such as prevention of psoriasis, body defense, immunity, and recovery.
본 발명에 따른 건강기능식품은 건선의 예방 또는 개선 목적으로, 분말, 과립, 정제, 캡슐, 시럽 또는 음료 등으로 제조될 수 있다. 상기 건강기능식품이 취할 수 있는 형태에는 제한이 없으며, 상기 약학 조성물과 동일한 방식으로 제제화되어 기능성 식품으로 이용하거나, 각종 식품에 첨가될 수 있다. The health functional food according to the present invention may be prepared in the form of powder, granules, tablets, capsules, syrups or beverages for the purpose of preventing or improving psoriasis. There is no limitation in the form that the health functional food can take, and it can be formulated in the same manner as the pharmaceutical composition and used as a functional food or added to various foods.
상기 건강기능식품은 통상적인 의미의 식품을 모두 포함할 수 있다. 예를 들어, 음료 및 각종 드링크, 과실 및 그의 가공식품(과일통조림, 잼 등), 어류, 육류 및 그 가공식품(햄, 베이컨 등), 빵류 및 면류, 쿠키 및 스낵류, 유제품(버터, 치즈 등) 등이 가능하며, 통상적인 의미에서의 기능성 식품을 모두 포함할 수 있다. 또한, 동물을 위한 사료로 이용되는 식품도 포함할 수 있다.The health functional food may include any food in a conventional sense. For example, beverages and various drinks, fruits and their processed foods (canned fruit, jam, etc.), fish, meat and their processed foods (ham, bacon, etc.), breads and noodles, cookies and snacks, dairy products (butter, cheese, etc.) ), etc. are possible, and may include all functional foods in a conventional sense. It may also include food used as feed for animals.
본 발명에 따른 건강기능식품 조성물은 당업계에서 통상적으로 사용되는 식품학적으로 허용 가능한 식품 첨가제(식품 첨가물) 및 적절한 기타 보조 성분을 더 포함하여 제조될 수 있다. 식품 첨가물로서의 적합 여부는 다른 규정이 없는 한, 식품의약품안전처에 승인된 식품첨가물공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정할 수 있다. 상기 '식품첨가물공전'에 수재된 품목으로는 예를 들어, 케톤류, 글리신, 구연산칼슘, 니코틴산, 계피산 등의 화학적 합성물; 감색소, 감초 추출물, 결정셀룰로오스, 고량색소, 구아검 등의 천연첨가물; L-글루타민산나트륨 제제, 면류첨가알칼리제, 보존료 제제, 타르색소제제 등의 혼합 제제류 등을 들 수 있다. The health functional food composition according to the present invention may be prepared by further including a pharmaceutically acceptable food additive (food additive) and other suitable auxiliary ingredients commonly used in the art. Unless otherwise specified, the suitability as a food additive can be determined according to the standards and standards for the relevant item in accordance with the general rules and general test methods of the Food Additives Code approved by the Ministry of Food and Drug Safety. The items listed in the 'Food Additives Codex' include, for example, chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; natural additives such as persimmon pigment, licorice extract, crystalline cellulose, high pigment, and guar gum; Mixed preparations, such as a sodium L-glutamate preparation, a noodle-added alkali agent, a preservative preparation, and a tar dye preparation, etc. are mentioned.
상기 기타 보조 성분은 예를 들어, 향미제, 천연 탄수화물, 감미제, 비타민, 전해질, 착색제, 펙트산, 알긴산, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산화제 등을 추가로 함유할 수 있다. 특히, 상기 천연 탄수화물로는 포도당, 과당과 같은 모노사카라이드, 말토스, 수크로오스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜을 사용할 수 있으며, 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다.The other auxiliary ingredients include, for example, flavoring agents, natural carbohydrates, sweeteners, vitamins, electrolytes, colorants, pectic acid, alginic acid, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents, etc. may further contain. In particular, as the natural carbohydrate, monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol can be used. , as the sweetener, natural sweeteners such as taumatine and stevia extract or synthetic sweeteners such as saccharin and aspartame may be used.
본 발명에 따른 건강기능식품에 함유된 상기 괭생이모자반 추출물의 유효 용량은 건선의 예방 또는 개선 등 그 사용 목적에 따라 적절하게 조절될 수 있다. The effective dose of the extract contained in the health functional food according to the present invention may be appropriately adjusted according to the purpose of its use, such as prevention or improvement of psoriasis.
상기 건강기능식품 조성물은 식품을 원료로 하여 일반 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어나, 건선 예방 또는 개선을 위한 보조제로 섭취될 수 있다.The health functional food composition has the advantage that there are no side effects that may occur during long-term administration of general drugs using food as a raw material, has excellent portability, and can be taken as an adjuvant for preventing or improving psoriasis.
이하, 본 발명의 이해를 돕기 위하여 실시예를 들어 상세하게 설명하기로 한다. 다만 하기의 실시예는 본 발명의 내용을 예시하는 것일 뿐 본 발명의 범위가 하기 실시예에 한정되는 것은 아니다. 본 발명의 실시예는 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.Hereinafter, to help the understanding of the present invention, examples will be described in detail. However, the following examples are merely illustrative of the content of the present invention, and the scope of the present invention is not limited to the following examples. The embodiments of the present invention are provided to more completely explain the present invention to those of ordinary skill in the art.
<실시예 1> 괭생이모자반 추출물 제조<Example 1> Preparation of hoesaengi hatban extract
괭생이모자반은 강원도 양양군에서 채집하여 수돗물을 이용하여 세척 후, -80℃에서 1일 동안 동결 보관 하였다. 동결 보관한 시료는 동결건조기를 이용하여 4일간 건조하였다. 건조 시료는 분쇄기를 이용하여 분쇄하여 분말 형태로 제조하였다. The hoesaeng hatban were collected from Yangyang-gun, Gangwon-do, washed with tap water, and then stored frozen at -80°C for 1 day. The frozen samples were dried for 4 days using a freeze dryer. The dry sample was pulverized using a pulverizer to prepare a powder.
분말 형태의 건조 시료에 70% 에탄올을 넣고 상온에서 1시간 동안 초음파 추출기로 8회 반복 추출하였다. 각 추출마다 여과지를 이용해 여과하였으며, 여과된 추출물은 감압 농축기를 이용하여 농축하였다. 농축된 시료는 완전한 건조를 위해 -80℃에서 동결 후 4~5일 동안 동결건조기를 이용하여 건조하였다. 건조된 추출물은 분말 형태로 만들어 실험에 사용하기 전까지 -80℃에서 동결 보관하였다. 70% ethanol was added to the dry sample in powder form, and extraction was repeated 8 times with an ultrasonic extractor at room temperature for 1 hour. Each extraction was filtered using a filter paper, and the filtered extract was concentrated using a vacuum concentrator. The concentrated sample was frozen at -80°C for complete drying and then dried using a freeze dryer for 4 to 5 days. The dried extract was made in powder form and stored frozen at -80°C until used in the experiment.
<실험예 1> 사람 피부각질세포(HaCaT keratinocytes)에서의 독성 확인<Experimental Example 1> Confirmation of toxicity in human skin keratinocytes (HaCaT keratinocytes)
세포 생존율 측정을 위해서 Cell counting kit-8 (CCK-8; Dogindo Laboratories, Japan) 시약을 이용하였다. 96-well 플레이트에 HaCaT 세포를 1×104 cells/100μl로 분주하여 8시간 동안 세포가 안정적으로 부착되면, 1% 페니실린/스트렙토마이신(penicillin/streptomycin)만 첨가되어진 DMEM 배지로 16시간 동안 바꿔주었다. 괭생이모자반 추출물을 여러 농도로 1시간 동안 전처리한 후, hTNF-α와 IFN-γ를 10 ng/ml로 24시간 동안 처리하였다. CCK-8 시약 10μl/well을 넣고 37℃ 배양기에서 1시간 동안 반응시킨 후, 마이크로플레이트 리더(microplate reader, SpectraMax M2/M2e Microplate Readers, moleculardevices, USA) 장비를 이용하여 450 nm 흡광도를 측정하였다. Cell counting kit-8 (CCK-8; Dogindo Laboratories, Japan) reagent was used to measure cell viability. HaCaT cells were dispensed in a 96-well plate at 1×10 4 cells/100 μl and when the cells were stably attached for 8 hours, 1% penicillin/streptomycin was added to DMEM medium for 16 hours. . After pre-treatment with various concentrations of the extracts of hoesaengi capricornis for 1 hour, hTNF-α and IFN-γ were treated at 10 ng/ml for 24 hours. 10 μl/well of CCK-8 reagent was added and reacted in an incubator at 37° C. for 1 hour, and then absorbance at 450 nm was measured using a microplate reader (SpectraMax M2/M2e Microplate Readers, moleculardevices, USA) equipment.
괭생이모자반 추출물을 처리한 모든 농도에서 (5, 30, 100μg/ml) 무처리군과 비교 시 유의적인 차이를 보이지 않아 세포의 생존율에 영향을 주지 않음을 확인하였다. 따라서 괭생이모자반 추출물은 처리한 농도 내에서 세포독성이 없는 것으로 사료되어 추후 실험에서 동일한 농도(5, 30, 100μg/ml)를 사용하여 실험을 진행하였다. At all concentrations (5, 30, 100 μg/ml) treated with the A. serrata extract, there was no significant difference compared with the untreated group, confirming that it did not affect the cell viability. Therefore, it is considered that the extracts of hoesaengnimojaban have no cytotoxicity within the treated concentration, so the experiment was carried out using the same concentrations (5, 30, 100 μg/ml) in a later experiment.
<실험예 2> 사람 피부각질세포를 이용한 건선 관련 병인인자의 생성억제 효능 확인<Experimental Example 2> Confirmation of the effect of inhibiting the generation of psoriasis-related etiological factors using human skin keratinocytes
괭생이모자반 추출물의 항건선 효능을 확인하고자 건선 관련 병인인자(IL-6, IL-8, TNF-α) 생성 억제 효능을 확인하였다. 염증이 유도된 HaCaT 세포로부터 생성된 염증 관련 사이토카인의 분비량 측정은 하기와 같이 실시하였다. In order to confirm the anti-psoriasis efficacy of the hoesaengnimojaban extract, the psoriasis-related etiological factors (IL-6, IL-8, TNF-α) production inhibitory efficacy was confirmed. The secretion amount of inflammation-related cytokines generated from inflammation-induced HaCaT cells was measured as follows.
DMEM 배지를 이용하여 24-well 플레이트에 5×104 cells/500μl로 세포를 분주하고 8시간 후, 1% 페니실린/스트렙토마이신만 첨가되어진 DMEM 배지로 바꾸어 16시간 동안 5% CO2 인큐베이터에서 18시간 동안 배양하였다. 여러 농도의 괭생이모자반 추출물을 1시간 전처리하고 hTNF-α와 IFN-γ를 10 ng/ml를 처리하여 24시간 배양하였다. 세포배양액 내의 TNF-α, IL-6 및 IL-8 사이토카인의 분비량을 ELISA kit (Max human ELISA set, Biolegend, San Diego, CA)를 이용하여 측정하였다. Cells were aliquoted at 5×10 4 cells/500 μl in a 24-well plate using DMEM medium, and after 8 hours, change to DMEM medium containing only 1% penicillin/streptomycin added, and 5% CO 2 in an incubator for 16 hours for 18 hours. incubated during Various concentrations of the extracts of hoesaengi capri were pre-treated for 1 hour, and hTNF-α and IFN-γ were treated with 10 ng/ml and cultured for 24 hours. The secretion of TNF-α, IL-6 and IL-8 cytokines in the cell culture was measured using an ELISA kit (Max human ELISA set, Biolegend, San Diego, CA).
이를 위해 캡쳐 항체 코팅(capture antibody coating)되어진 ELISA 마이크로플레이트에 배양 상층액을 분주하고 실온에서 2시간 반응시켰다. 반응 후 PBST로 세척하고 희석한 biotinylated anti-mouse TNF-α, IL-6 및 IL-8 검출 항체(detection antibody)와 streptavidin-horseradish peroxidase conjugate를 분주하여 실온에서 1시간 반응시켰다. To this end, the culture supernatant was dispensed on a capture antibody-coated ELISA microplate and reacted at room temperature for 2 hours. After the reaction, washed and diluted biotinylated anti-mouse TNF-α, IL-6 and IL-8 detection antibodies and streptavidin-horseradish peroxidase conjugate were dispensed and reacted at room temperature for 1 hour.
그 후 다시 PBST로 세척하고 TMB substrate solution을 첨가하여 실온에서 30분 동안 암반응시켰다. 반응 종료를 위해 stop solution을 분주한 뒤 마이크로플레이트 리더 (SpectraMax M2/M2e Microplate Readers, moleculardevices, USA) 장비를 이용하여 450 nm 흡광도를 측정하였다. After that, it was washed again with PBST, and TMB substrate solution was added, followed by dark reaction at room temperature for 30 minutes. After dispensing a stop solution to terminate the reaction, absorbance at 450 nm was measured using a microplate reader (SpectraMax M2/M2e Microplate Readers, moleculardevices, USA).
HaCaT 세포를 대상으로 하여 독성이 없는 농도로 설정 후, 건선 관련 병인인자 생성 억제 효능을 측정하기 위해 HaCaT 세포에 인위적으로 TNF-α+IFN-γ를 처리하여 세포가 분비하는 IL-6, IL-8, TNF-α생성을 과량으로 유도한 다음, 독성이 없는 농도 범위(5, 30, 100μg/ml)의 괭생이모자반 추출물을 처리하여 HaCaT 세포에서 분비하는 IL-6, IL-8, 및 TNF-α 생성 억제 효능을 ELISA Kit assay를 통하여 확인 결과, 도 1에 나타난 바와 같이, 괭생이모자반 추출물 농도 100μg/ml 과 30μg/ml 처리 농도에서 매우 우수한 IL-6 (A), IL-8 (B), TNF-α (C) 생성 억제 활성을 확인하였다. After setting the concentration of HaCaT cells to a non-toxic concentration, in order to measure the efficacy of inhibiting the generation of psoriasis-related etiological factors, HaCaT cells were artificially treated with TNF-α+IFN-γ to secrete IL-6 and IL- 8, IL-6, IL-8, and TNF secreted by HaCaT cells by inducing excessive TNF-α production, and then treating the non-toxic concentration range (5, 30, 100 μg/ml) As a result of confirming the -α production inhibitory effect through ELISA Kit assay, as shown in FIG. 1, very excellent IL-6 (A), IL-8 (B) ), TNF-α (C) production inhibitory activity was confirmed.
<실험예 3> 건선이 유발된 HaCaT 세포에서의 건선 억제조절 효능 확인 및 면역 관련 조절단백질 발현 양상 확인<Experimental Example 3> Confirmation of psoriasis inhibitory regulatory efficacy in psoriasis-induced HaCaT cells and confirmation of immune-related regulatory protein expression patterns
상기 실험예 2를 통해 괭생이모자반 추출물이 우수한 IL-6, IL-8 및 TNF-α의 생성 억제 활성을 확인한 바, 항건성 효능의 세포 신호 기전에 대해서도 확인하였다. 건선 유발 기전으로 알려진 세포내 인산화와 핵전사인자인 NF-κB를 조사하였다. Through the above Experimental Example 2, it was confirmed that the excellent production inhibitory activity of IL-6, IL-8 and TNF-α extract was confirmed, and the cell signaling mechanism of anti-drying efficacy was also confirmed. Intracellular phosphorylation and nuclear transcription factor NF-κB, known to induce psoriasis, were investigated.
HaCaT 세포를 1×105 cells/ml로 분주하여 8시간 동안 세포가 안정적으로 부착되면, 1% 페니실린/스트렙토마이신만 첨가되어진 DMEM 배지로 16시간 동안 바꿔주었다. 여기에 괭생이모자반 추출물을 처리하고, TNF-α와 IFN-γ를 10 ng/ml로 처리하였다. 각각 15분과 60분 후 배양이 끝난 세포를 수집하여 3회 phosphate buffered saline (PBS)으로 세척한 후, 전체적인 단백질은 cocktail inhibitor와 1M DTT, IM EDTA를 첨가시킨 mammalian lysis buffer로, 핵 안의 단백질은 NE-PER Nuclear and cytoplasmic Extraction reagents (THERMO SCIENTIFIC, IL)로 세포를 용해하여 단백질을 얻었다. When HaCaT cells were dispensed at 1×10 5 cells/ml and the cells were stably attached for 8 hours, they were replaced with DMEM medium supplemented with only 1% penicillin/streptomycin for 16 hours. Here, the extract was treated with the genus oleracea extract, and TNF-α and IFN-γ were treated at 10 ng/ml. After 15 and 60 minutes, respectively, the cells were collected and washed with phosphate buffered saline (PBS) three times. The total protein was a mammalian lysis buffer containing cocktail inhibitor, 1M DTT, and IM EDTA, and the protein in the nucleus was NE. Cells were lysed with -PER Nuclear and cytoplasmic Extraction reagents (THERMO SCIENTIFIC, IL) to obtain proteins.
Protein Assay Dye Reagent Concentrate (Bio-Rad)를 사용하여 단백질을 정량하였으며 30μg의 용해물(lysate)을 10% SDS-PAGE로 분리하였다. 전기영동한 겔은 0.45μm 니트로셀룰로오스 막(nitrocellulose membrane, MERCK)에 1시간 동안 전사시켜 5% skim milk가 함유된 tris-buffered saline (TBS, pH 7.5), 0.1% Tween 20 용액으로 상온에서 2시간 동안 blocking 하였다. Protein Assay Dye Reagent Concentrate (Bio-Rad) was used to quantify protein, and 30 μg of lysate was separated by 10% SDS-PAGE. The electrophoresed gel was transferred to a 0.45 μm nitrocellulose membrane (MERCK) for 1 hour, and then in tris-buffered saline (TBS, pH 7.5) containing 5% skim milk, 0.1% Tween 20 solution at room temperature for 2 hours. blocking while
인산화된 AKT, JNK, ERK, p38 및 AKT, JNK, ERK, p38, P65, actin의 발현 양을 검토하기 위하여 p-AKT, p-AKT, p-JNK, JNK, p-ERK, ERK, p-p38 및 p38 (Cell Signaling Technology Inc., USA), P65 (Thermo Fisher Scientific), actin (BD) 항체를 1:1000으로 희석하여 4C에서 16시간 반응시킨 후 Tris-Buffered Saline, 0.1% Tween 20 (TBST, pH 7.5)로 3회 세정하였다. 2차 항체로 horseradish peroxidase가 결합된 anti-mouse IgG 및 anti-rabbit IgG를 1:2,000으로 희석하여 상온에서 1시간 반응시킨 다음 TBST로 3회 세정하여 ECL 기질과 1~3분간 반응 후 각각의 단백질 밴드는 AI600 (GE Healthcare Bio-Sciences Corp., Marlborough, MA, USA)을 이용하여 가시화 하였다.To examine the expression levels of phosphorylated AKT, JNK, ERK, p38 and AKT, JNK, ERK, p38, P65, and actin, p-AKT, p-AKT, p-JNK, JNK, p-ERK, ERK, p- p38 and p38 (Cell Signaling Technology Inc., USA), P65 (Thermo Fisher Scientific), and actin (BD) antibodies were diluted 1:1000 and reacted at 4C for 16 hours, followed by Tris-Buffered Saline, 0.1% Tween 20 (TBST) , pH 7.5) was washed three times. As a secondary antibody, horseradish peroxidase-conjugated anti-mouse IgG and anti-rabbit IgG were diluted 1:2,000 and reacted at room temperature for 1 hour, washed 3 times with TBST, reacted with ECL substrate for 1 to 3 minutes, and then each protein Bands were visualized using an AI600 (GE Healthcare Bio-Sciences Corp., Marlborough, MA, USA).
염증 관련 대표적인 신호 기전인 MAPKs와 AKT를 조사한 결과, MAPKs 신호 기전은 억제 효능과는 관련되지 않았으나, 도 2에 나타난 바와 같이, AKT 신호 기전만이 억제 효능과 관련되어있는 세포 신호 기전임을 확인하였다. 또한, 핵전사인자인 NF-κB 활성을 유의하게 억제하는 것을 확인하였다. 괭생이모자반 추출물의 항건선 효능은 AKT와 NF-κB 신호 기전을 통하여 조절됨을 확인하였다.As a result of examining MAPKs and AKT, which are representative signaling mechanisms related to inflammation, the MAPKs signaling mechanism was not related to the inhibitory efficacy, but as shown in FIG. 2 , it was confirmed that only the AKT signaling mechanism was a cell signaling mechanism related to the inhibitory efficacy. In addition, it was confirmed that the nuclear transcription factor, NF-κB activity was significantly inhibited. It was confirmed that the anti-psoriasis efficacy of the extracts of hoesaengi capricornis was regulated through AKT and NF-κB signaling mechanisms.
<실험예 4> 건선 마우스 모델에서의 임상적 변화 확인<Experimental Example 4> Confirmation of clinical changes in psoriasis mouse model
이미퀴모드(Imiquimod, IMQ)를 이용한 건선 쥐 모델을 확립하였다. 약 6∼8주령의 수컷 Balb/c 생쥐 15마리를 오리엔트바이오 (성남, 대한민국)로부터 구입하였고, 제모기를 이용하여 등쪽 털을 제거한 후, 5% (62.5 mg/mouse) 이미퀴모드크림 (알다라 크림ⓡ, 동아에스티, 서울, 대한민국)을 도포하고, IMQ 도포한 후 4시간과 8시간 경과 후 2.5μg/mouse 칼시포트리올(calcipotriol, CAL, 건선치료물질), 0.5 mg/mouse 괭생이모자반 추출물을 하루 2번씩 7일 동안 도포하였다. 8일째에 홍반, 각질, 피부 두꺼워짐 등 건선의 임상적 변화를 육안으로 관찰하고, 피부조직을 채취하였다. A mouse model of psoriasis was established using Imiquimod (IMQ). 15 male Balb/c mice of about 6 to 8 weeks of age were purchased from Orient Bio (Seongnam, Korea), and after removing the dorsal hair using an epilator, 5% (62.5 mg/mouse) imiquimod cream (Aldara) Creamⓡ, Dong-A ST, Seoul, Korea) and 4 and 8 hours after IMQ application, 2.5μg/mouse calcipotriol (calcipotriol, CAL, psoriasis treatment substance), 0.5 mg/mouse was applied twice a day for 7 days. On the 8th day, clinical changes in psoriasis such as erythema, keratin, and skin thickening were visually observed, and skin tissues were collected.
육안평가는 아토피 피부염에서 사용되는 임상적 육안 평가 방법인 PASI (Psoriasis Area Severity Index)를 이용하였다 (Olivry 등 2007). PASI는 임상에서 아토피 피부염 증상의 심각성 정도를 측정하기 위해 널리 쓰이는 방법으로 고안된 것이다. 본 실험예에서는 도 3의 표에 나타난 바와 같이, 홍반(erythema), 각질(Scaling), 두께(Thickness)의 세 분야로 나누어 각각 0~4 단계까지 구분하였다. 각각 항목에 대해 증상 없음(0점), 약함(1점), 보통(2점), 심함(3점), 매우 심함(4점)으로 채점한 후, 평가하였다.For visual evaluation, the Psoriasis Area Severity Index (PASI), a clinical visual evaluation method used in atopic dermatitis, was used (Olivry et al. 2007). PASI was designed as a widely used method to measure the severity of symptoms of atopic dermatitis in clinical practice. In this experimental example, as shown in the table of FIG. 3, it was divided into three fields of erythema, Scaling, and Thickness, and divided into
연속 7일 동안 IMQ (62.5 mg/mouse)를 국소적으로 적용함으로써 BALB/c 마우스의 등 피부에 건선 피부 염증을 유도한 한 결과, 도 3에 나타난 바와 같이 정상적인 대조군 마우스와 비교하여, IMQ 도포로 유도한 건선 유사 병변의 증상은 뚜렷하게 나타났다. 기존에 알려진 건선 치료제인 CAL (calcipotriol, 2.5μg/mouse) 처리군에서는 IMQ 처리군에 비하여 유의한 건선 병변이 억제됨을 확인하였다. 괭생이모자반 추출물을 각 500μg 씩 도포한 실험군에서 IMQ 처리군에 비하여 병변의 뚜렷한 억제 효능을 확인하였다.As a result of inducing psoriatic skin inflammation on the back skin of BALB/c mice by topically applying IMQ (62.5 mg/mouse) for 7 consecutive days, as shown in FIG. 3 , compared with normal control mice, IMQ application The symptoms of the induced psoriasis-like lesion were evident. It was confirmed that significant psoriatic lesions were suppressed in the CAL (calcipotriol, 2.5 μg/mouse) treatment group, a known psoriasis treatment group, compared to the IMQ treatment group. In the experimental group, each of which was applied 500 μg of the extracts of hoesaengi capricornis, a distinct inhibitory effect on lesions was confirmed compared to the IMQ-treated group.
<실험예 5> 건선 마우스 모델에서의 피부의 조직학적 변화 확인<Experimental Example 5> Confirmation of histological changes of skin in psoriasis mouse model
피부조직 염색은 H&E stain (Hematoxylin & Eosin, Sigma-Aldrich Co.)으로 실시하였다. 피부조직 약 5×5 mm를 적출하여 4% 파라포름알데히드 (paraformaldehyde, pH 7.4, Sigma-Aldrich Co.)로 고정하고 일련의 과정을 통하여 파라핀 블록을 제작한 후, 5 μm 두께로 삭정하였다. 삭정한 조직 절편은 탈파라핀과 함수 과정을 거쳐 H&E로 염색하여 digital slide scanner (NanoZoomer 2.0-RS; Hamamatsu, Shizuoka, Japan)로 확인하였다.Skin tissue staining was performed with H&E stain (Hematoxylin & Eosin, Sigma-Aldrich Co.). About 5 × 5 mm of skin tissue was extracted, fixed with 4% paraformaldehyde (paraformaldehyde, pH 7.4, Sigma-Aldrich Co.), and paraffin blocks were prepared through a series of procedures, and then cut to a thickness of 5 μm. The trimmed tissue sections were deparaffinized and hydroused, stained with H&E, and confirmed with a digital slide scanner (NanoZoomer 2.0-RS; Hamamatsu, Shizuoka, Japan).
BALB/c 마우스의 등 피부에 건선 피부 염증을 유도한 후, 정상적인 대조군 마우스와 비교한 결과, 도 4에 나타난 바와 같이 IMQ 도포로 유도한 건선 유사 병변의 증상인 표피(epidermis)의 두께가 정상 마우스(CTRL) 보다 뚜렷하게 두께가 두껍게 나타났다. 기존에 알려진 건선 치료제인 CAL(calcipotriol, 2.5μg/mouse) 처리군에서는 IMQ 처리군에 비하여 표피의 두께가 유의하게 얇아진 것을 확인하였다. 괭생이모자반 추출물을 IMQ를 도포한 마우스 등 부위에 각 500μg 씩 도포한 실험군에서 IMQ 처리군에 비하여 전체 피부층 뿐 아니라, 표피의 두께가 유의하게 얇아진 것을 확인하였다.After inducing psoriasis skin inflammation on the back skin of BALB/c mice, as a result of comparison with normal control mice, as shown in FIG. 4 , the thickness of the epidermis, a symptom of psoriasis-like lesions induced by IMQ application, was normal in mice. (CTRL), the thickness was clearly thicker. In the CAL (calcipotriol, 2.5 μg/mouse) treatment group, which is a known psoriasis treatment group, it was confirmed that the thickness of the epidermis was significantly reduced compared to the IMQ treatment group. It was confirmed that in the experimental group, in which 500 μg of each 500 μg of the extract was applied to the back of the mouse to which IMQ was applied, not only the entire skin layer but also the thickness of the epidermis was significantly thinner than that of the IMQ-treated group.
이상으로 본 발명 내용의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적 기술은 단지 바람직한 실시양태일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 즉, 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의하여 정의된다.As described above in detail a specific part of the content of the present invention, for those of ordinary skill in the art, it is clear that this specific description is only a preferred embodiment, and the scope of the present invention is not limited thereby. do. That is, the substantial scope of the present invention is defined by the appended claims and their equivalents.
Claims (9)
상기 추출물은,
물, C1 내지 C4의 알코올 또는 이의 혼합물을 추출 용매로 하여 추출된 것을 특징으로 하는 건선 예방 또는 치료용 약학 조성물.The method of claim 1,
The extract is
A pharmaceutical composition for preventing or treating psoriasis, characterized in that it is extracted using water, C1 to C4 alcohol or a mixture thereof as an extraction solvent.
상기 추출물은,
각질세포의 염증 반응을 억제하는 것을 특징으로 하는 건선 예방 또는 치료용 약학 조성물.The method of claim 1,
The extract is
A pharmaceutical composition for preventing or treating psoriasis, characterized in that it inhibits the inflammatory response of keratinocytes.
상기 추출물은,
AKT 및 NF-κB 신호 기전을 통해 항건선 효능을 조절하는 것을 특징으로 하는 건선 예방 또는 치료용 약학 조성물.The method of claim 1,
The extract is
A pharmaceutical composition for preventing or treating psoriasis, characterized in that it modulates anti-psoriasis efficacy through AKT and NF-κB signaling mechanisms.
상기 추출물은,
피부 홍반(erythema), 피부 각질(scaling) 및 표피 조직 두께 증가로 이루어진 군에서 선택되는 하나 이상의 건선 유사 병변의 증상을 억제하는 것을 특징으로 하는 건선 예방 또는 치료용 약학 조성물.The method of claim 1,
The extract is
A pharmaceutical composition for preventing or treating psoriasis, characterized in that it suppresses the symptoms of one or more psoriasis-like lesions selected from the group consisting of skin erythema, skin scaling, and increased epidermal tissue thickness.
상기 건선은,
물방울 건선, 판상 건선, 홍피성 건선, 농포성 건선 및 박탈성 건선으로 이루어진 군에서 선택되는 하나 이상인 것을 특징으로 하는 건선 예방 또는 치료용 약학 조성물.The method of claim 1,
The psoriasis is
A pharmaceutical composition for preventing or treating psoriasis, characterized in that at least one selected from the group consisting of waterdrop psoriasis, plaque psoriasis, erythrodermic psoriasis, pustular psoriasis and exfoliative psoriasis.
상기 조성물은,
수성액, 겔, 연고, 크림, 로션, 페이스트, 도말제 및 패치로 이루어진 군에서 선택되는 어느 하나인 것을 특징으로 하는 건선 예방 또는 개선용 피부 외용제 조성물.8. The method of claim 7,
The composition is
An external composition for preventing or improving psoriasis, characterized in that it is any one selected from the group consisting of aqueous solutions, gels, ointments, creams, lotions, pastes, smears and patches.
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US20160310550A1 (en) * | 2012-04-02 | 2016-10-27 | Maruhachi Muramatsu, Inc. | METHOD FOR TREATING DISEASE ASSOCIATED WITH TRANSCRIPTION ACTIVATION BY NF-kB |
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US20160310550A1 (en) * | 2012-04-02 | 2016-10-27 | Maruhachi Muramatsu, Inc. | METHOD FOR TREATING DISEASE ASSOCIATED WITH TRANSCRIPTION ACTIVATION BY NF-kB |
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