KR20200081914A - A composition comprising extract of Prasiola japonica for preventing or treating for inflammatory skin diseases - Google Patents
A composition comprising extract of Prasiola japonica for preventing or treating for inflammatory skin diseases Download PDFInfo
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- KR20200081914A KR20200081914A KR1020180171925A KR20180171925A KR20200081914A KR 20200081914 A KR20200081914 A KR 20200081914A KR 1020180171925 A KR1020180171925 A KR 1020180171925A KR 20180171925 A KR20180171925 A KR 20180171925A KR 20200081914 A KR20200081914 A KR 20200081914A
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- Prior art keywords
- inflammatory skin
- preventing
- extract
- freshwater
- skin disease
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Abstract
Description
본 발명은 민물김 추출물을 유효성분으로 포함하는 염증성 피부 질환 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing or treating inflammatory skin diseases comprising fresh water kimchi extract as an active ingredient.
피부는 다양한 환경적인 요인에 대해 신체를 보호하는 물리적 장벽으로서 자외선 등의 물리적 자극, 혹은 화학적 자극으로부터 내부 장기를 보호하며 항상성을 유지하는데 중요한 역할을 하는 것으로(Athar, M., Indian J. Exp. Biol., 40(6), 656-667, 2002), 단순히 몸을 보호하는 보호막뿐 만 아니라 하나의 면역 기관으로 간주되고 있다(Seo, W. S. et al., Korean Society for Biotechnology and Bioenginnering Journal, 29(1), 36-41, 2014). Skin is a physical barrier that protects the body against a variety of environmental factors. It protects the internal organs from physical or chemical stimuli such as ultraviolet rays and plays an important role in maintaining homeostasis (Athar, M., Indian J. Exp. Biol., 40(6), 656-667, 2002), not only as a protective barrier to protect the body, but as an immune organ (Seo, WS et al., Korean Society for Biotechnology and Bioenginnering Journal, 29( 1), 36-41, 2014).
인간의 피부 구조는 크게 표피층(epidermis), 진피층(dermis), 피하지방층(subcutis)으로 나뉜다. 피부를 구성하는 세포들로는 표피층의 각질형성세포(keratinocyte), 멜라닌형성세포(melanocyte), 진피층의 섬유아세포(fibroblast), 그리고 피하지방층의 지방세포(fat cell)로 크게 나눌 수 있다. The human skin structure is largely divided into epidermis, dermis, and subcutis. The cells constituting the skin can be roughly divided into keratinocytes in the epidermal layer, melanocytes, fibroblasts in the dermal layer, and fat cells in the subcutaneous layer.
피부 각질형성세포는 표피세포의 대부분을 구성하는 성분으로서 각질을 형성하고 여러 사이토카인(cytokine)들을 생산하여 다양한 염증반응과 면역반응에 관여한다(Kim, N. M. et al., J. Ginseng Res., 31(2), 86-92, 2007; Beissert, S. et al., Clin. Exp. Rheumatol., 24(1 Suppl 40), S1-6, 2006). 피부 각질형성세포가 환경적, 생리적 스트레스에 노출되면 염증반응이 일어나고, 이로 인해 TNF-α(tumor necrosis factor-α), IFN-γ(interferon-γ), IL-1β(interleukin-1β), IL-6과 같은 여러 종류의 염증성 사이토카인들을 분비하게 된다(Kim, J. H. et al., The immunopathogenesis of psoriasis, Dermatol. Clin., 33, 13-23, 2015). Dermal keratinocytes are components that make up most of epidermal cells and form keratin and produce various cytokines to participate in various inflammatory and immune responses (Kim, NM et al., J. Ginseng Res., 31(2), 86-92, 2007; Beissert, S. et al., Clin.Exp.Rheumatol., 24(1 Suppl 40), S1-6, 2006). When skin keratinocytes are exposed to environmental and physiological stress, an inflammatory reaction occurs, which causes TNF-α (tumor necrosis factor-α), IFN-γ (interferon-γ), IL-1β (interleukin-1β), IL It releases several types of inflammatory cytokines such as -6 (Kim, JH et al., The immunopathogenesis of psoriasis, Dermatol. Clin., 33, 13-23, 2015).
또한, 염증 반응에서 중요한 역할을 하는 NF-κB(nuclear factor-kappa B)는 다양한 사이토카인, 케모카인(chemokine), 성장 인자(growth factor)의 합성을 조절하는 전사 인자(transcription factor)이다. NF-κB는 p50과 p65로 구성되어 핵 안으로 들어가 전사인자로서 작용하며, iNOS, COX-2 및 염증 관련 사이토카인을 합성하고, 일반적으로 세포질에서 IκBα(inhibitor NF-κBα)와 결합하여 NF-κB의 작용이 억제된다. 이들의 활성 조절은 염증반응을 조절하기 위한 핵심요소로서 NF-κB의 활성을 조절하여 염증 반응을 완화시키는 천연소재를 찾기 위한 연구가 활발히 진행되고 있다(강보경 등, Microbiol. Biotechnol. Lett., 43(2), 112-119, 2015).In addition, NF-κB (nuclear factor-kappa B), which plays an important role in the inflammatory response, is a transcription factor that regulates the synthesis of various cytokines, chemokines, and growth factors. NF-κB is composed of p50 and p65, enters the nucleus, acts as a transcription factor, synthesizes iNOS, COX-2 and inflammation-related cytokines, and binds NF-κB in general by binding to inhibitory NF-κBα (IκBα) in the cytoplasm. The action of is suppressed. The regulation of their activity is a key factor for controlling the inflammatory response, and studies have been actively conducted to find natural materials that modulate the activity of NF-κB to alleviate the inflammatory response (Kang Bo-kyung et al., Microbiol. Biotechnol. Lett., 43 (2), 112-119, 2015).
태양광선 중에 하나인 자외선은 200~400㎚ 사이 전자기적 스펙트럼 형태의 광선으로, 자외선 중에서도 인체와 직접적인 관련이 있는 파장대는 UVA와 UVB이다. UVA, UVB와 같은 자외선이 피부에 조사되면 체내에 있는 단백질이나 핵산 등의 광화학적 작용에 의해 비타민 D 합성, 상피 형성, 살균 효과 등이 이루어지나, 피부염, 피부암, 일광 화상, 색소 침착, 피부노화, 건조, 잔주름 등이 생기기도 한다.Ultraviolet rays, one of the sun's rays, are electromagnetic spectral rays between 200 and 400 nm. Among the ultraviolet rays, the wavelength bands directly related to the human body are UVA and UVB. When ultraviolet rays such as UVA and UVB are irradiated to the skin, vitamin D synthesis, epithelial formation, and sterilization effects are achieved by photochemical effects of proteins or nucleic acids in the body, but dermatitis, skin cancer, sunburn, pigmentation, and skin aging , Dryness, fine lines, etc.
자외선 조사로 인해 발생되는 피부의 급성 염증 반응은 일시적인 모세혈관의 확장, 모세혈관 벽의 투과성 증대에 의한 삼투현상이 발생됨으로써 나타나는 홍반 반응이 대표적이며, 급성 염증반응이 지나게 되면 멜라닌 세포의 생성이 증가되면서 유해한 자극으로부터 인체를 보호하는 반응인 색소 침착이 발생된다. 피부 면역을 담당하는 피부 세포들의 기능이 과활성화 되어 특정 면역인자들을 과량으로 분비하거나, 그 기능을 제대로 수행하지 못할 경우, 건선(psoriasis), 알레르기성 접속성 피부염(allergic contact dermatitis, ACD), 아토피 피부염(atopic dermatitis), 백반증(vitiligo) 등과 같은 다양한 염증성 피부 질환이 야기된다. Acute inflammatory reaction of the skin caused by UV irradiation is typical of erythema reaction caused by temporary expansion of capillaries and osmotic effects due to increased permeability of capillary walls, and the production of melanocytes increases when acute inflammatory reaction passes. As a result, pigmentation occurs, a reaction that protects the human body from harmful stimuli. If the functions of skin cells responsible for skin immunity are over-activated to secrete excessive amounts of certain immune factors, or if the function is not performed properly, psoriasis, allergic contact dermatitis (ACD), atopy Various inflammatory skin diseases, such as atopic dermatitis and vitiligo, are caused.
현재 염증성 피부 질환 치료제로써 스테로이드 제제, 국소 면역억제제, 국소 항생제 및 항히스타민 등이 사용되고 있으나, 상기 약물제제를 장기적으로 사용하는 경우 살이 트는 팽창선조, 피부위축, 모세혈관 확장, 스테로이드성 여드름, 다모증, 자반 등의 부작용이 일어날 수 있다. 특히 스테로이드제를 광범위한 부위에 바르면 피부를 통해 약제가 전신적으로 흡수되어 소아의 경우 성장을 방해할 수 있고, 성인은 골다공증과 같은 전신적인 부작용이 발생할 수 있다. 따라서, 천연물질로부터 유래되어 부작용이 적어 인체에 안전하면서도 염증성 피부 질환 개선 효과가 우수한 조성물의 개발이 필요한 실정이다.Steroid preparations, topical immunosuppressants, topical antibiotics, and antihistamines are currently used as treatments for inflammatory skin diseases, but when the drug is used for a long time, swelling swelling, skin atrophy, capillary expansion, steroid acne, hirsutism, purpura Side effects may occur. In particular, when steroids are applied to a wide range of areas, the drug can be absorbed systemically through the skin, which may interfere with growth in children, and in adults, systemic side effects such as osteoporosis may occur. Therefore, there is a need to develop a composition that is derived from natural materials and has fewer side effects, which is safe for the human body and has an excellent effect of improving inflammatory skin diseases.
민물김(Prasiola japonica)은 물김이라는 이름으로 구전되어 왔으며, 현대에 이르러 민물김으로 알려지고 있다. 민물김은 홍조류인 바다김과 달리 녹조류(Green algae, Phylum Chlorophyta)로서 바다가 아닌 민물에서 생육하며, 민물파래과(Prasiolacease)에 포함된다(Park, M. K. et al., J. Plant Bio., 13, 1-10, 1970). 일본에서는 민물김을 카와노리(하천김)라는 이름으로 부르고 있으며, 하천김과 같은 민물 조류를 인공배양하여 높은 상업적 이윤을 창출하고 있다. 우리나라 민물김은 1938년 일본 학자인 Okada가 함경남도 문천군 문천면에서 최초로 채취하여 Prasiola formosana var. coreana Okada로 명명하여 발표한 것이 효시이며(Okada, Y., J. Jpn. Bot., 15, 449-452, 1939), 삼척군의 집단에 대한 형태 및 생태학적 연구가 수행된 바가 있다(Park, M. K. et al., J. Plant Bio., 13, 1-10, 1970). 우리나라에서는 산업화에 따른 인위적 영향으로 40여 년 전에 이미 사라진 종으로 알려졌으나 아직 강원도 삼척시의 소한천에 민물김이 분포하고 있음이 밝혀졌다. Freshwater seaweed ( Prasiola japonica ) has been handed down under the name of water seaweed, and is known as freshwater seaweed in modern times. Unlike fresh seaweed, which is a red algae, freshwater seaweed is a green algae (Phylum Chlorophyta) that grows in freshwater, not in the sea, and is included in the freshwater paraphysis (Park, MK et al., J. Plant Bio., 13, 1-10, 1970). In Japan, freshwater seaweed is called kawanori (river stream seaweed) and artificial commercial culture of freshwater algae such as stream seaweed creates high commercial profits. Korean freshwater seaweed was first collected in 1938 by a Japanese scholar, Okada, from Muncheon-myeon, Muncheon-gun, Hamgyeongnam-do, in Prasiola formosana var. It was published in the name of coreana Okada and was published (Okada, Y., J. Jpn. Bot., 15, 449-452, 1939), and morphological and ecological studies of the Samcheok group have been conducted (Park, MK et al., J. Plant Bio., 13, 1-10, 1970). In Korea, it has been known that the species disappeared more than 40 years ago due to the artificial influence of industrialization, but it has been found that freshwater seaweed is still distributed in Socheon, Samcheok-si, Gangwon-do.
민물김과 같은 녹조류 유래 추출물은 항고혈압 및 미코스포린-유사 아미노산(mycosporine-like amino acids, MAAs)에 의한 자외선 차단 등의 활성을 가지는 것으로 보고된 바 있으며(Cha, S. H. et al., J. Korean Soc. Food Sci. Nutr., 35, 307-314, 2006; Groniger, A. et al., J. Photochem. Photobiol. B., 66, 54-59, 2002), 일본에서 민물유래 식용김으로 사용하고 있는 스이젠지노리(Suizenzinori, Aphanothece sacrum)에는 고 함량의 철분 및 칼슘 등 미네랄 성분이 풍부한 것으로 조사되어 약리학적 활용도가 높게 평가된 바 있다(Ngatu, N. R. et al., Ann. Allergy Asthma Immunol., 108, 117-122, 2012). 그러나, 국내 자생 민물김에 대한 생리활성물질 성분분석 및 약리학적 분석에 대한 연구는 아직까지 많이 이루어지지 않고 있는 실정이다.Green algae-derived extracts, such as freshwater seaweed, have been reported to have antihypertensive and UV-blocking activity by mycosporine-like amino acids (MAAs) (Cha, SH et al., J. Korean) Soc. Food Sci. Nutr., 35, 307-314, 2006; Groniger, A. et al., J. Photochem.Photobiol. B., 66, 54-59, 2002), used as freshwater-derived seaweed in Japan Suizenzinori ( Aphanothece sacrum ) has been found to be rich in minerals such as high content of iron and calcium, and has been highly evaluated for pharmacological utilization (Ngatu, NR et al., Ann.Allergy Asthma Immunol., 108 , 117-122, 2012). However, studies on the analysis of physiologically active substance components and pharmacological analysis of native freshwater seaweed have not been conducted so far.
민물김 추출물을 포함하는 염증성 피부 질환과 관련된 종래선행문헌으로서, 선행문헌 [Seo, D. W. et al., J. Biomed. Res., 14(2), 83-90, 2013] 및 [Sa, J. H. et al., Rep. Inst. Health & Environ., 25, 52-62, 2014]에는 민물김 추출물의 생리활성(항암 효과, 항염증 효과, 항산화 효과, 항당뇨 효과, 자외선 차단효과)이 개시되었으며, 한국등록특허 제10-1853687호에는 방사무늬김 추출물의 항염증 조성물이 개시되었고, 한국등록특허 제10-1015702호에는 해조류 추출물의 염증 및 피부자극 개선용 조성물이 개시된 바 있다. 그러나, 본 발명과 같이 민물김 추출물이 염증성 피부 질환의 예방 또는 치료 효과가 있음을 언급한 이전 보고는 아직 없다. As a prior art literature related to inflammatory skin diseases, including freshwater seaweed extract, prior literature [Seo, D. W. et al., J. Biomed. Res., 14(2), 83-90, 2013] and [Sa, J. H. et al., Rep. Inst. Health & Environ., 25, 52-62, 2014] disclosed the physiological activity (anti-cancer effect, anti-inflammatory effect, anti-oxidative effect, anti-diabetic effect, sunscreen effect) of freshwater seaweed extract, and Korean Patent Registration No. 10-1853687 The anti-inflammatory composition of the radiation pattern seaweed extract was disclosed in Korean Patent No. 10-1015702, and a composition for improving inflammation and skin irritation of seaweed extract has been disclosed. However, there have been no previous reports that the freshwater seaweed extract as in the present invention has the effect of preventing or treating inflammatory skin diseases.
본 발명의 목적은 민물김 추출물을 유효성분으로 포함하는 염증성 피부 질환 예방 또는 치료용 조성물을 제공하는데 있다. An object of the present invention is to provide a composition for preventing or treating inflammatory skin diseases comprising freshwater kimchi extract as an active ingredient.
본 발명은 민물김(Prasiola japonica) 추출물을 유효성분으로 포함하는 염증성 피부 질환 예방 또는 치료용 약학 조성물에 관한 것이다. The present invention relates to a pharmaceutical composition for the prevention or treatment of inflammatory skin diseases comprising freshwater seaweed ( Prasiola japonica ) extract as an active ingredient.
상기 민물김은 녹조류로 홍조류인 바다김과는 달리 바다가 아닌 민물에서 생육하며, 민물파래과(Prasiolacease)에 속한다. The freshwater seaweed is a green algae, and unlike red seaweed, seaweed, grows in fresh water, not in the sea, and belongs to the freshwater parasaceae.
상기 민물김 추출물은 민물김을 물, C1 내지 C4의 저급 알코올, 아세톤, 헥산, 디클로로메탄 및 에틸아세테이트로 이루어진 군에서 선택되는 1종 이상의 용매로 추출하여 얻을 수 있으며, 상기 C1 내지 C4의 저급 알코올로는 메탄올, 에탄올, 프로판올, 이소프로판올, 부탄올 및 이소부탄올로 이루어진 군에서 선택될 수 있고, 바람직하게는 에탄올을 사용한다. The freshwater seaweed extract can be obtained by extracting freshwater seaweed with one or more solvents selected from the group consisting of water, lower alcohols of C1 to C4, acetone, hexane, dichloromethane and ethyl acetate, and lower alcohols of C1 to C4 The furnace may be selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol and isobutanol, preferably ethanol.
또한, 상기 추출물의 추출시간은 특별히 제한되는 것은 아니나, 10분 내지 1일 이내에 추출하는 것이 바람직하며, 추출용 기기로는 통상의 추출기기, 초음파분쇄추출기 또는 분획기를 이용할 수 있다. In addition, the extraction time of the extract is not particularly limited, it is preferable to extract within 10 minutes to 1 day, as an extraction device, a conventional extraction device, an ultrasonic pulverizer or a fractionator may be used.
상기 염증성 피부 질환은 자외선에 의해 유도되는 것을 특징으로 하며, 구체적으로는 건선, 아토피성 피부염, 알레르기성 피부염, 지루성 피부염, 접촉성 피부염, 여드름, 전신 홍반성 루프스 및 두드러기로 이루어진 군에서 선택된다.The inflammatory skin disease is characterized by being induced by ultraviolet rays, and is specifically selected from the group consisting of psoriasis, atopic dermatitis, allergic dermatitis, seborrheic dermatitis, contact dermatitis, acne, systemic lupus erythematosus and urticaria.
본 발명 민물김 추출물은 약학 조성물 총 중량에 대하여 바람직하게는 0.001중량% 내지 50중량%, 더 바람직하게는 0.001중량% 내지 40중량%, 가장 바람직하게는 0.001중량% 내지 30중량%로 첨가될 수 있다. The freshwater seaweed extract of the present invention may be added in an amount of preferably 0.001% to 50% by weight, more preferably 0.001% to 40% by weight, and most preferably 0.001% to 30% by weight relative to the total weight of the pharmaceutical composition. have.
본 발명에 따른 약학 조성물은 일반적으로 사용되는 약학적으로 허용 가능한 담체와 함께 적합한 형태로 제형화될 수 있다. "약학적으로 허용 가능"이란 생리학적으로 허용되고 인간에게 투여될 때, 통상적으로 위장 장애, 현기증 등과 같은 알레르기 반응 또는 이와 유사한 반응을 일으키지 않는 조성물을 말한다. 또한, 상기 조성물은 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있으며, 바람직하게는 경구용 투여제, 스프레이제, 겔제, 연고제, 크림제 또는 외용제로 제형화하여 사용될 수 있다.The pharmaceutical composition according to the present invention may be formulated in a suitable form together with a commonly used pharmaceutically acceptable carrier. “Pharmaceutically acceptable” refers to a composition that is physiologically acceptable and does not cause an allergic reaction or similar reaction, such as gastrointestinal disorders, dizziness, etc., when administered to a human. In addition, the composition may be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injectable solutions, respectively, according to a conventional method. Preferably, it can be used in the form of oral dosage forms, sprays, gels, ointments, creams or external preparations.
상기 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토오스, 덱스트로즈, 수크로스, 소르비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아라비아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로오스, 미결정셀룰로오스, 폴리비닐 피롤리돈, 물, 파라옥시벤조산메틸, 파라옥시벤조산프로필, 탈크, 스테아르산마그네슘 및 광물유를 포함할 수 있으나, 이에 한정되는 것은 아니다. 제제화할 경우에는 보통 사용하는 충진제, 안정화제, 결합제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 본 발명의 추출물에 적어도 하나 이상의 부형제, 예를 들면, 전분, 미결정셀룰로오스, 수크로스 또는 락토오스, 저치환도히드록시프로필셀룰로오스, 히프로멜로오스 등을 섞어 조제된다. 또한 단순한 부형제 이외에 스테아르산마그네슘, 탈크 같은 활택제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 유동파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁용제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세롤, 젤라틴 등이 사용될 수 있다. 비경구 투여용 제형으로 제제화하기 위하여 상기 추출물 또는 이의 약학적으로 허용되는 염을 멸균되고/되거나 방부제, 안정화제, 수화제 또는 유화 촉진제, 삼투압 조절을 위한 염 및/또는 완충제 등의 보조제, 및 기타 치료적으로 유용한 물질과 함께 물에 혼합하여 용액 또는 현탁액으로 제조하고, 이를 앰플 또는 바이알 단위 투여형으로 제조할 수 있다.Carriers, excipients and diluents that can be included in the composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl Cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl paraoxybenzoate, propyl paraoxybenzoate, talc, magnesium stearate, and mineral oil may be included, but is not limited thereto. In the case of formulation, it is prepared using diluents or excipients such as fillers, stabilizers, binders, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations include at least one excipient in the extract of the present invention, for example, starch, microcrystalline cellulose, sucrose or lactose, It is prepared by mixing low-substituted hydroxypropyl cellulose and hypromellose. Also, in addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use include suspensions, intravenous solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used, various excipients, such as wetting agents, sweetening agents, fragrances, and preservatives, can be included. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and suppositories. As non-aqueous solvents and suspensions, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin, glycerol, gelatin, etc. may be used. Adjuvants such as sterile and/or preservatives, stabilizers, hydrating or emulsifying accelerators, salts and/or buffers for osmotic pressure control, and other treatments of the extract or its pharmaceutically acceptable salts for formulation into parenteral dosage forms. It can be prepared as a solution or suspension by mixing in water with a useful substance, and it can be prepared in ampoules or vials.
본 발명에 개시된 추출물을 유효성분으로 포함하는 약학 조성물은 쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내 주사에 의해 투여될 수 있다. 투여량은 치료받을 대상의 연령, 성별, 체중, 치료할 특정 질환 또는 병리 상태, 질환 또는 병리 상태의 심각도, 투여시간, 투여경로, 약물의 흡수, 분포 및 배설률, 사용되는 다른 약물의 종류 및 처방자의 판단 등에 따라 달라질 것이다. 이러한 인자에 기초한 투여량 결정은 당업자의 수준 내에 있으며, 일반적으로 투여량은 0.01㎎/㎏/일 내지 대략 2000㎎/㎏/일의 범위이다. 더 바람직한 투여량은 1㎎/㎏/일 내지 500㎎/㎏/일이다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. The pharmaceutical composition comprising the extract disclosed in the present invention as an active ingredient may be administered to various mammals, such as rats, livestock, and humans. Any mode of administration can be envisaged, for example, oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dura or cerebrovascular injection. The dosage is the age, gender, weight of the subject to be treated, the specific disease or pathology to be treated, the severity of the disease or pathology, the time of administration, the route of administration, the absorption, distribution and excretion rate of the drug, the type of other drug used and the prescriber's It will depend on the judgment. Dosage determination based on these factors is within the level of those skilled in the art, and the dosage is generally in the range of 0.01 mg/kg/day to approximately 2000 mg/kg/day. A more preferred dosage is 1 mg/kg/day to 500 mg/kg/day. The administration may be administered once a day, or may be divided into several times. The above dosage does not limit the scope of the present invention in any way.
또 다른 일면에 있어서, 본 발명은 민물김(Prasiola japonica) 추출물을 유효성분으로 포함하는 염증성 피부 질환 예방 또는 개선용 건강기능식품에 관한 것이다.In another aspect, the present invention relates to a health functional food for preventing or improving inflammatory skin disease, including freshwater seaweed ( Prasiola japonica ) extract as an active ingredient.
상기 건강기능식품은 유용한 기능성을 가진 원료나 성분을 사용하여 제조 또는 가공한 식품을 지칭하는 것으로, 예를 들어 건강보조식품, 기능성 식품, 영양제, 보조제 등을 모두 포함한다. The health functional food refers to food manufactured or processed using ingredients or ingredients having useful functionality, and includes, for example, health supplements, functional foods, nutritional supplements, and supplements.
상기 추출물은 전체 건강기능식품 총 중량에 대하여 바람직하게는 0.001중량% 내지 50중량%, 더 바람직하게는 0.001중량% 내지 30중량%, 가장 바람직하게는 0.001중량% 내지 10중량%로 하여 첨가될 수 있다. 본 발명의 건강기능식품은 정제, 캡슐제, 환제 또는 액제 등의 형태를 포함하며, 본 발명 추출물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제 등이 있다.The extract may be added in an amount of preferably 0.001% to 50% by weight, more preferably 0.001% to 30% by weight, and most preferably 0.001% to 10% by weight relative to the total weight of the dietary supplement. have. The health functional food of the present invention includes tablets, capsules, pills or liquids, and foods to which the extract of the present invention can be added, for example, various foods, beverages, gums, teas, vitamin complexes, etc. There is this.
본 발명은 민물김 추출물을 유효성분으로 포함하는 염증성 피부 질환 예방 또는 치료용 조성물에 관한 것이다. 상기 민물김 추출물은 자외선에 의해 유도된 피부 염증 억제 효과가 우수하므로, 염증성 피부 질환의 치료용 조성물로 유용하게 사용될 수 있다.The present invention relates to a composition for preventing or treating inflammatory skin diseases comprising fresh water kimchi extract as an active ingredient. The freshwater seaweed extract is excellent in inhibiting skin inflammation induced by ultraviolet rays, and thus can be usefully used as a composition for the treatment of inflammatory skin diseases.
도 1은 자외선에 의해 염증이 유도된 HaCaT 세포에서의 민물김 추출물(Pj-EE) 처리에 따른 COX-2, IL-1β 및 IL-8의 mRNA 발현량 변화를 확인한 결과이다.
도 2는 자외선에 의해 염증이 유도된 HaCaT 세포에서의 민물김 추출물(Pj-EE) 처리에 따른 IL-6, TNF-α 및 IFN-γ의 mRNA 발현량 변화를 확인한 결과이다.
도 3은 자외선에 의해 염증이 유도된 HaCaT 세포에서의 민물김 추출물(Pj-EE) 처리에 따른 IκBα, P65 및 P50와 인산화된 IκBα, P65 및 P50의 단백질 발현량 변화를 확인한 결과이다. 1 is a result of confirming a change in mRNA expression levels of COX-2, IL-1β and IL-8 according to freshwater seaweed extract (Pj-EE) treatment in HaCaT cells in which inflammation is induced by UV light.
Figure 2 is a result confirming the mRNA expression changes of IL-6, TNF-α and IFN-γ according to freshwater seaweed extract (Pj-EE) treatment in inflammation-induced HaCaT cells by UV.
3 is a result of confirming changes in protein expression levels of IκBα, P65 and P50 and phosphorylated IκBα, P65 and P50 according to freshwater seaweed extract (Pj-EE) treatment in HaCaT cells in which inflammation is induced by UV light.
이하 본 발명의 바람직한 실시예를 상세히 설명하기로 한다. 그러나 본 발명은 여기서 설명되는 실시예에 한정되지 않고 다른 형태로 구체화될 수도 있다. 오히려, 여기서 소개되는 내용이 철저하고 완전해지고, 당업자에게 본 발명의 사상을 충분히 전달하기 위해 제공하는 것이다.Hereinafter, a preferred embodiment of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein and may be embodied in other forms. Rather, the contents introduced herein are thorough and complete, and are provided to sufficiently convey the spirit of the present invention to those skilled in the art.
<실시예 1. 민물김 추출물 제조><Example 1. Preparation of freshwater seaweed extract>
본 발명의 민물김(Prasiola japonica)은 삼척시에서 채취한 민물김을 사용하였다. Freshwater seaweed ( Prasiola japonica ) of the present invention used freshwater seaweed collected from Samcheok City.
삼척시에서 채취한 민물김은 불순물들을 제거하기 위해 수돗물로 세척하였고, 70%[v/v] 에탄올을 이용하여 살균 처리 후, 증류수로 세척하여 동결 건조하였다. 동결 건조한 민물김을 곱게 파쇄하고, 파쇄된 민물김 100g에 80%[v/v] 에탄올 1ℓ을 넣고 실온에서 24시간 동안 침지시켰다. 이러한 과정을 3회 반복하여 얻은 추출액을 와트만 여과지(filter paper)로 여과시킨 후, 증발기(evaporator)를 이용하여 용매를 증발시켜 민물김 추출물을 확보하였다. Freshwater seaweed collected from Samcheok City was washed with tap water to remove impurities, and sterilized using 70% [v/v] ethanol, followed by washing with distilled water and freeze-dried. The freeze-dried freshwater seaweed was finely crushed, and 1 l of 80% [v/v] ethanol was added to 100 g of freshly crushed freshwater seaweed and immersed at room temperature for 24 hours. After filtering the extract obtained by repeating this
<실시예 2. HaCaT 세포의 배양><Example 2. Culture of HaCaT cells>
HaCaT(human keratinocyte cell) 세포는 10% FBS(fetal bovine serum)와 1% 페니실린(penicillin) 및 100U/㎖의 스트렙토마이신(streptomycin)을 첨가한 DMEM(Dulbecco's Modified Medium) 배지를 사용하여, 37℃, 5% CO₂조건에서 계대 배양하여 실험에 사용하였다. Human keratinocyte cell (HaCaT) cells were cultured at 37° C. using DMEM (Dulbecco's Modified Medium) medium containing 10% fetal bovine serum (FBS), 1% penicillin, and 100 U/ml streptomycin. It was used for the experiment by subculturing in 5% CO2 condition.
<실시예 3. 피부 염증 억제 효과 확인><Example 3. Confirmation of skin inflammation inhibitory effect>
피부세포에서의 본 발명 민물김 추출물 처리에 따른 염증 억제 효과를 확인하기 위해, COX-2, IL-1β, IL-6, IL-8, TNF-α 및 IFN-γ의 mRNA 발현과 IκBα, P65 및 P50의 단백질 발현을 확인하였다.In order to confirm the effect of inhibiting inflammation according to the treatment of the freshwater seaweed extract in the skin cells, mRNA expression of COX-2, IL-1β, IL-6, IL-8, TNF-α and IFN-γ and IκBα, P65 And protein expression of P50.
상기 실시예 2에서 배양한 HaCaT 세포를 6웰 플레이트에 웰당 8×105개의 세포가 되도록 분주하여 24시간 동안 배양하였다. 이후, UVB(317nm) 램프로 30mJ/cm2의 UVB를 조사하여 피부 염증을 유도하고, 민물김 추출물을 농도별(50, 100, 200㎍/㎖)로 처리하여 24시간 동안 배양하였다. 상기 세포로부터 COX-2, IL-1β, IL-6, IL-8, TNF-α 및 IFN-γ의 mRNA 발현과 IκBα, P65 및 P50의 단백질 발현을 확인하여, 도 1 내지 3에 나타내었다.Seeded per well such that the
도 1 내지 3을 살펴보면, 자외선 처리하여 피부 염증이 유도된 HaCaT 세포에 민물김 추출물을 처리하는 경우 COX-2, IL-1β, IL-6, IL-8, TNF-α 및 IFN-γ의 mRNA 발현과 인산화된 IκBα, P65 및 P50의 단백질 발현이 농도 의존적으로 감소하여 염증 반응이 감소됨을 알 수 있었다. 또한, 도면에는 나타내지 않았으나 본 발명 민물김 추출물은 대식세포(RAW 264.7 세포) 보다 피부세포(HaCaT 세포)에서 특히 더 선택적으로 염증 반응을 억제하였다. 이로부터 본 발명 민물김 추출물은 자외선에 의해 유도된 염증성 피부 질환의 치료용 조성물로 유용하게 사용될 수 있음을 알 수 있었다.Looking at Figures 1 to 3, when treated with freshwater seaweed extract in skin inflammation-induced HaCaT cells by UV treatment, COX-2, IL-1β, IL-6, IL-8, TNF-α and IFN-γ mRNA It was found that the expression and phosphorylated protein expression of IκBα, P65 and P50 are concentration-dependently reduced, thereby reducing the inflammatory response. In addition, although not shown in the figure, the freshwater seaweed extract of the present invention suppressed the inflammatory response more selectively in skin cells (HaCaT cells) than macrophages (RAW 264.7 cells). From this, it was found that the freshwater seaweed extract of the present invention can be usefully used as a composition for the treatment of inflammatory skin diseases induced by ultraviolet rays.
<제제예 1. 약학적 제제><Formulation Example 1. Pharmaceutical preparation>
제제예 1-1. 친수성 연고제의 제조Formulation Example 1-1. Preparation of hydrophilic ointment
본 발명 실시예 1의 민물김 추출물을 이용하여, 하기 표 1에 기재된 조성에 따라 통상의 방법으로 친수성 연고제를 제조하였다. Using the freshwater seaweed extract of Example 1 of the present invention, a hydrophilic ointment was prepared by a conventional method according to the composition shown in Table 1 below.
제제예 1-2. 정제의 제조Formulation Example 1-2. Preparation of tablets
본 발명 실시예 1의 민물김 추출물을 이용하여, 하기 표 2에 기재된 성분을 혼합한 후, 통상의 정제 제조방법에 따라서 타정하여 정제를 제조하였다.Using the freshwater seaweed extract of Example 1 of the present invention, after mixing the components shown in Table 2, tablets were prepared by tableting according to a conventional tablet manufacturing method.
<< 제제예Formulation example 2. 건강기능식품의 제조> 2. Production of health functional food>
본 발명 실시예 1의 민물김 추출물 20g, 비타민 혼합물 적량, 비타민 A 아세테이트 70㎍, 비타민 E 1.0㎎, 비타민 B1 0.13㎎, 비타민 B2 0.15㎎, 비타민 B6 0.5㎎, 비타민 B12 0.2㎍, 비타민 C 10㎎, 비오틴 10㎍, 니코틴산아미드 1.7㎎, 엽산 50㎍, 판토텐산 칼슘 0.5㎎, 무기질 혼합물 적량, 황산제1철 1.75㎎, 산화아연 0.82㎎, 탄산 마그네슘 25.3㎎, 제1인산칼륨 15㎎, 제2인산칼슘 55㎎, 구연산칼륨 90㎎, 탄산칼슘 100㎎, 염화마그네슘 24.8㎎을 섞어 과립으로 제조하였으나, 용도에 따라 다양한 제형으로 변형시켜 제조할 수 있다. 또한, 상기의 비타민 및 미네랄 혼합물의 조성비를 임의로 변형 실시하여도 무방하며, 통상의 건강기능식품 제조방법에 따라 상기의 성분을 혼합하여 제조할 수 있다.20 g of freshwater seaweed extract of Example 1 of the present invention, a suitable amount of vitamin mixture, 70 μg of vitamin A acetate, 1.0 mg of vitamin E, 0.13 mg of vitamin B1, 0.15 mg of vitamin B2, 0.5 mg of vitamin B6, 0.2 μg of vitamin B12, and 10 mg of vitamin C ,
<< 제제예Formulation example 3. 건강기능성 음료의 제조> 3. Production of health functional beverages>
본 발명 실시예 1의 민물김 추출물 1g, 구연산 0.1g, 프락토올리고당 100g, 정제수 900g을 섞어 통상의 음료 제조방법에 따라 교반, 가열, 여과, 살균, 냉장하여 음료를 제조하였다.A beverage was prepared by mixing 1 g of freshwater seaweed extract of Example 1 of the present invention, 0.1 g of citric acid, 100 g of fructooligosaccharide, and 900 g of purified water, followed by stirring, heating, filtering, sterilizing, and refrigerating according to a conventional beverage preparation method.
Claims (10)
상기 민물김 추출물은 민물김을 물, C1 내지 C4의 저급 알코올, 또는 이들의 혼합용매로 추출 및 농축하여 얻은 것을 특징으로 하는 염증성 피부 질환 예방 또는 치료용 약학 조성물. According to claim 1,
The freshwater seaweed extract is a pharmaceutical composition for preventing or treating inflammatory skin diseases, characterized in that freshwater seaweed is obtained by extraction and concentration with water, a lower alcohol of C1 to C4, or a mixed solvent thereof.
상기 염증성 피부 질환은 자외선에 의해 유도되는 것을 특징으로 하는 염증성 피부 질환 예방 또는 치료용 약학 조성물. According to claim 1,
The inflammatory skin disease is a pharmaceutical composition for preventing or treating inflammatory skin disease, characterized in that induced by ultraviolet rays.
상기 염증성 피부 질환은 건선, 아토피성 피부염, 알레르기성 피부염, 지루성 피부염, 접촉성 피부염, 여드름, 전신 홍반성 루프스 및 두드러기로 이루어진 군에서 선택되는 것을 특징으로 하는 염증성 피부 질환 예방 또는 치료용 약학 조성물. According to claim 1,
The inflammatory skin disease is psoriasis, atopic dermatitis, allergic dermatitis, seborrheic dermatitis, contact dermatitis, acne, systemic erythematous lupus and urticaria inflammatory skin disease prevention or treatment pharmaceutical composition characterized in that selected from the group consisting of.
상기 약학 조성물의 제형은 경구용 투여제, 스프레이제, 겔제, 연고제, 크림제 또는 외용제로 이루어진 군에서 선택되는 것을 특징으로 하는 염증성 피부 질환 예방 또는 치료용 약학 조성물. According to claim 1,
The pharmaceutical composition of the pharmaceutical composition for the prevention or treatment of inflammatory skin diseases, characterized in that the formulation is selected from the group consisting of oral dosage forms, sprays, gels, ointments, creams or external preparations.
상기 민물김 추출물은 민물김을 물, C1 내지 C4의 저급 알코올, 또는 이들의 혼합용매로 추출 및 농축하여 얻은 것을 특징으로 하는 염증성 피부 질환 예방 또는 개선용 건강기능식품. The method of claim 6,
The freshwater seaweed extract is a health functional food for preventing or improving inflammatory skin diseases, characterized in that freshwater seaweed is obtained by extracting and concentrating with water, a lower alcohol of C1 to C4, or a mixed solvent thereof.
상기 염증성 피부 질환은 자외선에 의해 유도되는 것을 특징으로 하는 염증성 피부 질환 예방 또는 개선용 건강기능식품. The method of claim 6,
The inflammatory skin disease is a health functional food for preventing or improving inflammatory skin disease, characterized in that induced by ultraviolet rays.
상기 염증성 피부 질환은 건선, 아토피성 피부염, 알레르기성 피부염, 지루성 피부염, 접촉성 피부염, 여드름, 전신 홍반성 루프스 및 두드러기로 이루어진 군에서 선택되는 것을 특징으로 하는 염증성 피부 질환 예방 또는 개선용 건강기능식품. The method of claim 6,
The inflammatory skin disease is psoriasis, atopic dermatitis, allergic dermatitis, seborrheic dermatitis, contact dermatitis, acne, systemic lupus erythematosus lupus and urticaria, characterized in that selected from the group consisting of inflammatory skin disease prevention or improvement health functional food .
상기 건강기능식품의 제형은 정제, 캡슐제, 환제 또는 액제로 이루어진 군에서 선택되는 것을 특징으로 하는 염증성 피부 질환 예방 또는 개선용 건강기능식품. The method of claim 6,
The formulation of the health functional food is a health functional food for preventing or improving inflammatory skin disease, characterized in that selected from the group consisting of tablets, capsules, pills or liquids.
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