KR101882736B1 - Composition for skin protection comprising melatonin, vitamin C and pycnogenol as effective ingredient - Google Patents
Composition for skin protection comprising melatonin, vitamin C and pycnogenol as effective ingredient Download PDFInfo
- Publication number
- KR101882736B1 KR101882736B1 KR1020170087258A KR20170087258A KR101882736B1 KR 101882736 B1 KR101882736 B1 KR 101882736B1 KR 1020170087258 A KR1020170087258 A KR 1020170087258A KR 20170087258 A KR20170087258 A KR 20170087258A KR 101882736 B1 KR101882736 B1 KR 101882736B1
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- Prior art keywords
- melatonin
- skin
- vitamin
- composition
- cytotoxicity
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- A61K8/4913—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
- A61K8/492—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid having condensed rings, e.g. indol
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Abstract
본 발명은 피부 보호용 조성물에 관한 것으로서, 보다 상세하게는 자유라디칼(free radical)을 소거하는 항산화 효과를 지니는 멜라토닌을 유효 성분으로 함유한 피부보호용 조성물에 관한 것이다. 본 발명의 피부 보호용 조성물은 UV-A 및 B와 H2O2와 화학물질로부터 피부 손상을 막아줌으로 피부보호가 뛰어나다.The present invention relates to a skin protecting composition, and more particularly, to a skin protecting composition containing melatonin as an active ingredient having an antioxidative effect of eliminating free radicals. The skin protection composition of the present invention is excellent in skin protection by preventing skin damage from UV-A and B, H 2 O 2 and chemicals.
Description
본 발명은 멜라토닌, 비타민 C 및 피크노제놀을 유효 성분으로 함유한 피부보호용 조성물에 관한 것이다.The present invention relates to a skin protecting composition containing melatonin, vitamin C and pycnogenol as an active ingredient.
일반적으로 활성산소종 (ROS: reactive oxygen species)은 높은 반응성을 나타내는 작은 분자들로서, UV나 특정 약물 등에 의해 생성되며, superoxide (O2·-), hydrogen peroxide (H2O2) 및 highly reactive hydroxyl (OH·) radical 등이 포함된다. 세포 내에서 일정 농도의 활성산소종은 유익한 역할을 수행하는 것으로 알려져 있으나, 과다하게 존재할 경우 세포생존에 악영향을 끼칠 수 있다. 이러한 활성산소종 중 H2O2 (hydrogen peroxide, 과산화수소)는 거의 모든 oxygen radical들로부터 생성되기 때문에 중요하게 여겨지고 있다. 높은 농도의 H2O2는 세포 안팎의 단백질, 지질, DNA와 같은 macromolecule들을 변형시켜 세포를 파괴하며, 그것으로 인해서 세포자살 (apoptosis)이나 세포괴사 (necrosis)와 같은 세포사를 유도한다고 보고되어 있다(Barbouti A, Free Rad Biol Med 33: 691702, 2002).In general, reactive oxygen species (ROS: reactive oxygen species) are as small molecules having a high reactivity is produced by UV or certain drugs, superoxide (O2 · -), hydrogen peroxide (H 2 O 2) , and highly reactive hydroxyl ( OH ·) radical. Although a certain concentration of reactive oxygen species is known to play a beneficial role in cells, excessive presence of such reactive oxygen species may adversely affect cell viability. Among these active oxygen species, H 2 O 2 (hydrogen peroxide) is considered to be important because it is generated from almost all oxygen radicals. High concentrations of H 2 O 2 have been reported to modify macromolecules such as proteins, lipids, and DNA inside and outside cells to destroy cells and thereby induce apoptosis or cell death such as necrosis (Barboutia, Free Rad Biol Med 33: 691702, 2002).
UV나 특정 약물 등은 피부 내의 활성산소종 생성을 유도하며, 이러한 활성산소종 생성은 피부의 상피세포 (epidermal cells)에 부정적인 효과를 나타낸다. 현재 피부세포 내 활성산소종 생성에 대한 예방 혹은 치료에 관한 연구가 광범위하게 진행되고 있으며, 그 중 대표적인 하나가 노화와 관련된 연구이다. 사람들은 아주 오래 전부터 노화를 늦추는 것에 대한 관심을 많이 가져왔고, 노화의 진행 속도를 늦추기 위한 그 메커니즘에 대한 연구가 최근까지 이어지고 있다. 그 결과 여러 가지 노화의 원인들이 제시되고 있고, 활성산소종이 그 원인 중 하나로 여겨지고 있다. 더 나아가, 미백은 피부미용에 있어 노화만큼 지속적인 관심이 이어져오고 있는 분야이며, UV 등에 의해 생성된 활성산소종은 피부세포에서 멜라닌 생성을 유도 할 수 있으며 이러한 멜라닌 생성을 억제하는 연구가 활발히 진행되고 있다(Hedley SJ, Pigment Cell Res 15: 4956, 2003 / HIROSHI YANASE, PIGMENT CELL RES 14: 103-109. 2001 / Brozyna AA, Int J Cancer 15;123(6):1448-56, 2008).UV or certain drugs induce the production of reactive oxygen species in the skin, and such production of reactive oxygen species has a negative effect on skin epidermal cells. Currently, studies on preventing or treating the production of reactive oxygen species in skin cells have been extensively carried out, and a representative example thereof is research related to aging. People have been very interested in slowing aging for a long time, and research into the mechanism to slow the progression of aging has been up to date. As a result, various causes of aging are being suggested, and active oxygen species is considered to be one of the causes. In addition, whitening is a field that has been continuing as much interest in skin care as aging, and active oxygen species produced by UV light can induce melanogenesis in skin cells, and studies to suppress such melanin production have been actively conducted (Hedley SJ, Pigment Cell Res 15: 4956, 2003 / HIROSHI YANASE, PIGMENT CELL RES 14: 103-109, 2001 / Brozyna AA, Int J Cancer 15; 123 (6): 1448-56, 2008).
피부는 외부 환경으로부터 신체를 보호하는 1차 보호시스템이기 때문에 물리, 화학적인 외부 물질에 끊임없이 노출되고 있다. 피부는 보호 기능, 장벽 기능, 온도 조절 기능, 배설 기능, 호흡 기능 등을 하는 기관으로, 표피, 진피, 피하지방으로 이루어 진다. 표피는 가장 얇은 층으로 각질 형성 세포와 멜라닌 세포의 유기적인 결합으로 이루어져 있다. 진피는 피부의 약 95%를 차지하며 피부의 보습 및 보호를 담당하는 층으로, 피부탄력(주름)에 중요한 역할을 하는 대표적인 단백질인 콜라겐, 엘라스틴이 그물처럼 짜여져 있고, 혈관과 신경이 존재하며, 알레르기 반응에 관여하는 비만세포, 및 Na-PCA 또는 히아루론산 등의 천연 보습 인자도 함유하고 있다. 피하 지방은 표피 및 진피로의 영양 공급, 체형 결정, 체온 유지, 외부적인 충격 흡수 및 피하지방하 세포 보호 등의 역할을 한다.Since skin is the primary protection system for protecting the body from the external environment, it is constantly exposed to physical and chemical external substances. The skin is composed of epidermis, dermis, and subcutaneous fat. It has protective function, barrier function, temperature control function, excretion function, and respiratory function. The epidermis is the thinnest layer composed of organic bonds of keratinocytes and melanocytes. The dermis is responsible for moisturizing and protecting the skin, which accounts for about 95% of the skin. Collagen and elastin, which are important proteins in skin elasticity (wrinkles), are woven like nets, blood vessels and nerves exist, Mast cells involved in allergic reactions, and natural moisturizing factors such as Na-PCA or hyaluronic acid. Subcutaneous fat plays a role in supplying nutrients to the epidermis and dermis, body shape, maintaining body temperature, absorbing external shocks, and protecting subcutaneous fat cells.
이러한 피부는 나이가 들면서 내인성 또는 외인성 원인으로 인해 피부기능이 급격히 저하되는 노화를 겪게 된다. 노화가 진행되면서 피부의 구성 성분인 표피, 진피, 및 피하 지방의 두께가 얇아지고 콜라겐과 엘라스틴이 가늘어지고 느슨해져 탄력이 떨어지고 주름 등이 생긴다. 또한, 피부장벽의 기능을 맡고 있는 지질 장벽(Lipid barrier)의 지질 조성과 함량이 변화하면서 피부의 수분함량이 떨어지고 피부가 건조해지는 등의 생리적 변화를 겪게 된다. 또한, 기미, 주근깨, 색소 침착과 그 외 다양한 피부 병변이 유발된다.Such skin undergoes an aging process in which skin function is rapidly deteriorated due to intrinsic or extrinsic causes as the skin ages. As the aging progresses, the thickness of the epidermis, dermis, and subcutaneous fat, which are constituents of the skin, becomes thinner, and collagen and elastin become thin and loose, resulting in decreased elasticity and wrinkles. In addition, the lipid composition and content of the lipid barrier, which is responsible for the function of the skin barrier, undergo a physiological change such as a decrease in the moisture content of the skin and dryness of the skin. In addition, spots, freckles, pigmentation and various other skin lesions are induced.
이런 피부노화에 따른 문제점을 해결하기 위하여 피부개선 효과를 가지는 다양한 유효 성분과 이를 포함하는 조성물이 연구되어지고 있다.In order to solve the problems caused by aging of the skin, various active ingredients having skin improving effect and compositions containing the active ingredients have been studied.
피부노화를 억제시키는 효과가 있는 성분으로는 비타민 C, 비타민 E, 베타카로틴 등 항산화 비타민 등이 많이 사용되고 있다. 이중, 비타민 C는 자외선(UV) 차단 효과, 항산화 효과, 콜라겐 형성 촉진을 통한 피부 주름 개선, 기미/주근깨/검버섯 등의 색소 침착개선 효과, 면역체계 강화 등을 갖는 것으로 알려져 있다. 이와 같은 비타민 C의 작용을 요약하면 다음과 같다.Antioxidant vitamins such as vitamin C, vitamin E and beta-carotene are widely used as ingredients that inhibit skin aging. Vitamin C is known to have ultraviolet (UV) blocking effect, antioxidant effect, improvement of skin wrinkle through promotion of collagen formation, improvement of pigmentation such as spots / freckles / black spots, and strengthening of immune system. The action of vitamin C is summarized as follows.
비타민 C는 자외선, 특히 UV A에 대한 차단기능이 강하다 (Darr, D. et al., 1996, Acta Derm. Venereol. (Strckh). 76: 264-268; Black, H. S. et al., 1975, J. Invest. Dermatol. 65: 412-414). 또한, 비타민 C는 UV B에 의해 발생하는 피부 손상을 보호하는 역할을 하는데, UV B 조사전에 비타민 C를 돼지와 인간의 피부에 바르고 여기에 UV B를 조사하면 홍반과 햇볕에 타는 현상이 방지된다는 사실이 밝혀졌다 (Darr, D. et al., 1992, Brit. J. Dermatil. 127: 247-253; Murry, J. et al., 1991, J. Invest. Dermatol. 96: 587).Vitamin C has a strong blocking action against ultraviolet light, especially UV A (Darr, D. et al., 1996, Acta Derm. Venereol. (Strckh.) 76: 264-268; Black, HS et al., 1975, J Invest. Dermatol., 65: 412-414). Vitamin C also protects against skin damage caused by UVB. Vitamin C is applied to pigs and human skin before UVB irradiation, and UVB is applied to prevent erythema and sunburn (Darr, D. et al., 1992, Brit. J. Dermatil. 127: 247-253; Murry, J. et al., 1991, J. Invest. Dermatol. 96: 587).
비타민 C는 피부, 혈액 및 기타 조직에서 화학적 오염, 흡연, 특히 자외선(UV)에 의해 유발되는 활성산소종(Reactive Oxygen Species, ROS)를 중화시키는 강력한 생체 항산화제로서의 작용을 하며, 이와 같은 효과는 비타민 C가 두개의 전자를 받아들여 탈수소-L-아스코르브산(Dehydro-L-ascorbic acid) 형태로 쉽게 산화될 수 있는 구조에 기인하는 것이다. 비타민 C는 피부의 비효소적 항산화제 방어 시스템의 중요한 요소로 비타민 C가 고농도로 존재할 때 싱글렛 산소(singlet oxygen), 슈퍼옥사이드 음이온(superoxide anion), 하이드록시 라디칼(hydroxy radical)과 같은 ROS 등이 단백질, 핵산, 세포막 지질 등의 생체 성분을 산화시키거나 변성시키기 전에 이들을 중화시키는 역할을 하는 것이다 (Buettner, G. R. et al. 1996. Cadenas, E., Packer, L., eds. Handbook of antioxidants. pp. 91-115).Vitamin C acts as a powerful biocompatible antioxidant that neutralizes reactive oxygen species (ROS) caused by chemical pollution, smoking, especially ultraviolet light (UV) in skin, blood and other tissues. It is due to the structure that vitamin C accepts two electrons and can be easily oxidized in the form of dehydro-L-ascorbic acid. Vitamin C is an important component of the skin's nonenzymatic antioxidant defense system. It is a major source of vitamin C when it is present in high concentration, such as singlet oxygen, superoxide anion, ROS such as hydroxy radical (Buettner, GR et al. 1996. Cadenas, E., Packer, L., eds. Handbook of antioxidants.), Which is used to neutralize biological components such as proteins, nucleic acids and cell membrane lipids before they are oxidized or denatured. pp. 91-115).
또한, 비타민 C는 각질층으로 경피적으로 공급됨으로써 피부 광택, 피부색 개선, 주름 감소, 탄력 증가 등의 효과를 가지며 (미국 특허 제4,983,382호), 이러한 효과는 비타민 C에 의해 콜라겐 합성이 촉진되기 때문에 얻어지는 것이다. 콜라겐 폴리펩타이드의 10% 정도를 차지하는 히드록시프롤린은 프롤린 하이드록실라제(proline hydroxylase)에 의해 생합성되는데, 상기 효소의 보조인자(cofactor)로 비타민 C가 작용한다 (Tomita, Y. et al., 1980, J. Invest. Dermatol. 75(5): 379-382). 즉, 비타민 C는 프롤린 하이드록실라제의 활성을 촉진하여 하이드록실프롤린의 합성을 촉진하고, 이는 삼중나선 구조의 콜라겐 생합성을 촉진하여 피부 주름 형성 억제 등의 피부 개선 효과를 가지는 것이다.In addition, vitamin C is supplied percutaneously to the stratum corneum, thereby obtaining skin luster, skin color improvement, wrinkle reduction, and elasticity increase (U.S. Patent No. 4,983,382), and this effect is obtained because vitamin C promotes collagen synthesis . Hydroxyproline, which accounts for about 10% of the collagen polypeptide, is biosynthesized by proline hydroxylase. Vitamin C functions as a cofactor of the enzyme (Tomita, Y. et al. 1980, J. Invest. Dermatol 75 (5): 379-382). That is, vitamin C promotes the activity of proline hydroxylase to promote the synthesis of hydroxyl proline, which promotes collagen biosynthesis of the triple helix structure, thereby improving skin such as inhibition of the formation of wrinkles.
또한, 비타민 C는 우수한 미백 효과를 가지며, 이러한 효과는 비타민 C가 멜라닌 형성에 중요한 티로시나아제(tyrosinase) 활성과 멜라닌 형성을 억제하기 때문에 얻어지는 것이다 (Tomita, Y. et al., 1980, J. Invset. Dermatol. 75(5); 379-382).In addition, vitamin C has an excellent whitening effect, and this effect is obtained because vitamin C inhibits tyrosinase activity and melanin formation, which are important for melanin formation (Tomita, Y. et al., 1980, J. Invet Dermatol, 75 (5), 379-382).
또한, 비타민 C는 면역체계를 강화시키는 효과를 가지며, 이는 비타민 C가 알러지 반응물질인 히스타민의 세포막에서의 방출을 억제함으로써 민감성 피부에서의 알러지 반응을 억제함으로써 나타나는 것이며, 쥐에서 항원에 접촉시 자외선 유도된 면역억제와 내성으로부터 보호한다는 것이 증명되었다(Nakamura, T. et al., 1997, J. Invest. Dermatol. 109: 20-24). 또한, 비타민 C는 백혈구의 식균작용을 도와주고 감염이 전개되는 동안 백혈구 이동을 촉진시켜 감염을 억제하고 바이러스 증식 억제 물질인 인터페론의 생합성을 증가시키는 작용을 하여, 다양한 감염성 질환에 대한 생체 저항성을 상승시키는 역할도 한다. 그 외 비타민 C는 생체내 엽산 대사 및 아미노산의 대사 과정에도 관여하는 등 다양한 기능을 수행한다.In addition, vitamin C has the effect of enhancing the immune system. This is because vitamin C inhibits allergic reactions in sensitive skin by inhibiting the release of histamine in the cell membrane of the allergic reaction substance, and ultraviolet (Nakamura, T. et al., 1997, J. Invest. Dermatol. 109: 20-24). In addition, vitamin C helps leukocyte phagocytosis, promotes leukocyte migration during infection development, inhibits infection, increases the biosynthesis of interferon, which is a virus inhibiting substance, and increases the bio resistance against various infectious diseases It also plays a role. Vitamin C also plays a diverse role in the metabolism of folic acid and amino acids in vivo.
한편, 멜라토닌은 세로토닌을 전구체로 하여 합성되는 송과체 호르몬으로 24시간 주기 리듬(circadian rhythm)을 조절한다고 알려져 있다. 멜라토닌은 동물, 식물, 미생물에서 발견되는 항산화물질로 특히, 식물 중에는 토마토, 포토 껍질, 타트 체리, 호두 등의 일반적인 야채에 많이 분포되어 있다. 신체에서는 뇌간에 있는 송과선에서 분비되며, 낮에 햇빛에 노출되어야 생성되고, 밤에 분비가 가능하다. 뿐만 아니라, 잠을 자는 동안 상처 치유를 비롯한 생리학적 변화가 생긴다 (Assessment of sleep patterns, energy expenditure and circadian rhythms of skin temperature in patients with acute coronary syndrome, 2011, med sci monit 17, CR397-403).On the other hand, melatonin is known to regulate circadian rhythm with pineal gland hormone synthesized from serotonin as a precursor. Melatonin is an antioxidant found in animals, plants and microorganisms. Especially, it is distributed in common vegetables such as tomatoes, photo peels, tart cherries and walnuts in plants. In the body, it is secreted from the pineal gland in the brainstem, produced by exposure to sunlight during the day, and secreted at night. In addition, during sleep, there is a physiological change, including wound healing (Energy expenditure and circadian rhythms of skin temperature in patients with acute coronary syndrome, 2011, med sci monit 17, CR397-403).
최근 항산화(anti-oxidant effect) 기능이 강하여 여러 질병을 완화시키는 치료법과 자외선 차단제로 접근된다 (Melatonin: action as antioxidant and potential applications in human disease and aging, 2010, toxicology 278, 55-67 ; Antioxidant properties of melatonin and its potential action in diseases, 2015, curr topmed chem 15, 894-903).Recently, anti-oxidant effect is strong and it is approached as a treatment and a sunscreen that alleviate many diseases (Melatonin: action as antioxidant and potential applications in human disease and aging, 2010, toxicology 278, 55-67; Antioxidant properties of melatonin and its potential action in diseases, 2015, curr topmed chem 15, 894-903).
항산화 이외에도 미토콘드리아의 기능을 향상시켜 (New Evidence for Cross Talk between Melatonin and Mitochondria Mediated by a Circadian-Compatible Interaction with Nitric Oxide, 2013, int. j. mol. Sci 14, 11259-11276) 세포의 구조 강화 (Melatonin as a cytoskeletal modulator: implications for cell physiology and disease, 2006, j pineal res 40, 1-9) 및 재생 치유에도 (hysiological Regeneration of Skin Appendages and Implications for Regenerative Medicine, 2012, physiology 27, 61-72 ; Melatonin reduces ultraviolet-B induced cell damages and polyamine levels in human skin fibroblasts in culture, 2003, exp mol med, 35, 263-268) 관여한다고 보고되었다. 이 멜라토닌에는 크게 3가지의 기능을 갖는다.In addition to antioxidants, it also improves the function of mitochondria (New Evidence for Melatonin and Mitochondria Mediated by a Circadian-Compatible Interaction with Nitric Oxide, 2013, Int. J. Mol. Sci 14, 11259-11276) (2006), p. 29.), and also to regenerative healing (Hysiology of Skin Appendages and Implications for Regenerative Medicine, 2012, physiology 27, 61-72; Melatonin reduction 2003, Exp Mole Med, 35, 263-268). In addition, it has been reported that microvascular endothelial growth factor This melatonin has three main functions.
① 비타민 E의 2배의 활성을 갖는 항산화 효과① Antioxidant effect with twice the activity of vitamin E
② 노화신경 퇴행과정 지연을 통한 노화방지② Prevention of aging by delaying aging process
③ 생체시계 조절을 통한 신체리듬 조절③ Body rhythm control by controlling the biological clock
멜라토닌은 강력한 항산화제로 노화방지 효과가 뛰어나고 항염효과가 있는 활성성분임에도 수용성 화장품 활성약물 및 제1, 제2 유용성(oil-soluble) 화장품용 활성약물, 피부 침투 증강제를 포함하는 피부 국소 화장품용 조성물에 제2 유용성 활성약물로 사용되는 특허(국소 화장품용 조성물, 출원번호:10-2004-7021353, 출원인: 코즈메스틱 솔루션즈프로퍼티 리미티드)가 있으나, 이 경우에는 국소 화장품용으로 한정되어지며, 멜라토닌은 사용 가능한 많은 활성성분 중 항산화제 및 자유라디칼 소거제 중 한가지로서 첨가 가능한 경우이고 피부침투 증강제를 통한 활성성분이 각질층으로 전달하는 결과를 가져오는 것을 주요 기술로 하다. 이와 같이, 멜라토닌은 강력한 항산화제로 노화방지 효과가 뛰어나고 항염효과가 있는 활성성분임에도 피부 보호용 의약품으로서 연구가 미미한 수준이다.Melatonin is a powerful antioxidant and has excellent antioxidative and anti-inflammatory properties. However, melatonin is an active ingredient for skin topical cosmetics containing active ingredients for water-soluble cosmetics, active ingredients for first and second oil-soluble cosmetics, and skin permeation enhancer There is a patent (topical cosmetic composition, Application No. 10-2004-7021353, Applicant: Cosmestic Solutions Properties Limited) used as a second oil-soluble active drug, but in this case it is limited to local cosmetics and melatonin is used It is possible to add as one of antioxidant and free radical scavenging agent as much as possible, and it is a main technique that the active ingredient through the skin permeation enhancer is delivered to the stratum corneum. Thus, although melatonin is a powerful antioxidant, it has excellent anti-aging effect and anti-inflammatory active ingredient, but its research as a skin protection drug is minimal.
또한, 피크노제놀은 프랑스 남서부에 있는 보르도지방에 서식하는 해송(Pinus maritima) 껍질에서 추출한 물질의 브랜드명이다. 보르도 대학 명예교수인 작 마스케리에 박사는 47년에 프랑스 해송껍질에서 폴리페놀의 일종인 OPC(Oligomeric Proantho Cyanidin)를 비롯하여 여러 종류의 기능성 성분을 발견, 추출하는데 성공했다. 피크노제놀의 주성분인 OPC는 소나무가 환경유독물질이나 기후상태에서 스스로를 지켜주는 항산화물질이다. 프랑스 해송은 비스케 해안의 모진 바람으로부터 스스로를 지키기 위해 강력한 항산화 물질을 만들어 내는 것이다. 피크노제놀은 우수한 항산화작용(미국특허 제4,698,360호)과 혈관보호작용(미국특허 제5,720,956호)이 있는 소재로 인정받아 현재 미국을 비롯한 여러 나라에서 건강식품으로 이용되고 있으며 프랑스에서는 이미 68년에 혈관보호 약으로 승인을 받아 '플라반(Flavan)'이란 상품명으로 판매되고 있다.Pycnogenol is also a brand name for the material extracted from the bark of Pinus maritima in the Bordeaux region in southwestern France. Professor Emeritus Professor Dr. Masar Kerry of Bordeaux University succeeded in discovering and extracting various functional ingredients, including Oligomeric Proantho Cyanidin (OPC), a type of polyphenol in French sea shells. OPC, the main component of pycnogenol, is an antioxidant that protects pine trees against environmental toxins and weather conditions. The French sea shoals produce powerful antioxidants to protect themselves from the winds of the Viste coast. Pycnogenol has been recognized as an excellent antioxidant (US Patent No. 4,698,360) and vasoprotective action (US Patent No. 5,720,956) and is currently used as a health food in the United States and other countries. In France, Approved as medicine and sold under the brand name 'Flavan'.
피크노제놀은 피부에 있어서 미세 혈류를 증가시켜 상처의 회복에 크게 역할을 하고 있다. 또한 피크노제놀은 하이드록시프롤린(hydroxyproline)에 대한 강력한 친화성이 있어 콜라겐(collagen)과 엘라스틴(elastin) 합성에 큰 기여를 하고 있다. 결과적으로 피크노제놀은 피부의 자유라디칼 손상 및 효소 분해(enzymatic degradation)로부터 이들 단백질을 보호해 준다. Pycnogenol plays a major role in the recovery of wounds by increasing microfiltration in the skin. In addition, pycnogenol has a strong affinity for hydroxyproline, which contributes greatly to the synthesis of collagen and elastin. As a result, pycnogenol protects these proteins from free radical damage and enzymatic degradation of the skin.
피크노제놀 단독 또는 프랑스해안송껍질 추출물(피크노제놀)에 비타민 C, 비타민 E, 달맞이꽃종자유를 혼합한 원료는 기능성원료로 인정받았지만 피크노제놀이 다른 건강 보조물과 혼합된 경우의 효능에 대해서는 알려지지 않았다.Pycnogenol alone or in combination with the French coastal pine bark extract (pycnogenol) in combination with vitamin C, vitamin E and evening primrose oil has been recognized as a functional ingredient, but the efficacy of pycnogenol in combination with other health aids is not known.
이에, 본 발명자들은 종래부터 공지된 멜라토닌의 항산화 효과 이외에 멜라토닌이 피부 세포의 기능을 향상시킴으로써 자외선의 손상으로부터 빠르게 회복시킬 수 있으며, 여기에 피크노제놀 및 비타민 C가 복합적으로 사용되는 경우 그 약리 효과 및 효능이 향상된 피부보호 효과를 확인함으로써 본 발명을 완성하였다.In addition to the antioxidant effect of melatonin which is conventionally known, the inventors of the present invention have found that melatonin improves the function of skin cells so that it can be quickly recovered from damage of ultraviolet rays. When pycnogenol and vitamin C are used in combination, their pharmacological effect and efficacy And confirming the improved skin protection effect, thereby completing the present invention.
본 발명의 목적은 멜라토닌, 비타민 C 및 피크노제놀을 유효 성분으로 함유한 피부보호용 조성물에 관한 것이다. 구체적으로, 본 발명은 세포들을 빔(beam)으로 조사시켰을 때, 피부 손상으로부터 빠른 회복을 유도하는 멜라토닌을 유효성분으로 함유하는 조성물에 관한 것이다.An object of the present invention is to provide a skin protecting composition containing melatonin, vitamin C and pycnogenol as an active ingredient. Specifically, the present invention relates to a composition containing melatonin as an active ingredient, which induces rapid recovery from skin damage when cells are irradiated with a beam.
상기 목적을 달성하기 위하여, 본 발명은 멜라토닌을 유효 성분으로 함유한 피부보호용 조성물을 제공한다. In order to achieve the above object, the present invention provides a composition for skin protection comprising melatonin as an active ingredient.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명의 피부보호용 조성물에 있어서, 상기 조성물은 멜라토닌 이외에 비타민 C와 피크노제놀을 추가적으로 함유하는 것이 바람직하고, 멜라토닌 이외에 비타민 C와 피크노제놀(pycnogenol)을 추가적으로 함유하는 것이 바람직하면, 이때 상기 조성물은 조성물 전체 중량에 대하여 멜라토닌 5~40 중량, 비타민 C 30~80중량% 및 피크노제놀 5~40중량%인 것이 보다 바람직하다.In the skin protecting composition of the present invention, the composition preferably contains vitamin C and pycnogenol in addition to melatonin. When the composition further contains vitamin C and pycnogenol in addition to melatonin, More preferably 5-40 weight percent of melatonin, 30-80 weight percent of vitamin C and 5-40 weight percent of pycnogenol.
본 발명의 피부보호용 조성물에 있어서, 상기 조성물은 2회 이상 처리에 의해 UV 또는 화학적 물질로부터 피부를 보호하는 것이 바람직하고, 이때, 상기 UV는 UV-A 또는 UV-B인 것이 보다 바람직하고, 상기 UV는 2회 이상 조사되는 것이 보다 바람직하다. 아울러, 상기 화학적 물질은 H2O2, superoxide (O2·-) 및 하이드록시 라디칼(OH·)로 구성되는 군으로부터 선택된 물질인 것이 바람직하고, H2O2인 것이 가장 바람직하다.In the skin protecting composition of the present invention, it is preferable that the composition protects the skin from UV or chemical substances by treating the skin more than twice. More preferably, the UV is UV-A or UV-B, It is more preferable that UV is irradiated twice or more. In addition, the chemical substance is H 2 O 2, superoxide (O2 · -) and the hydroxy radical preferably a material selected from the group consisting of (OH ·), and most preferably in the H 2 O 2.
본 발명에서 "피부 보호"란 피부세포가 증식되고, 피부세포 내의 활성산소종 증가가 현저하게 억제되고, H2O2 등에 의해 유도되던 세포사멸이 억제 되는 것을 의미한다.In the present invention, "skin protection" means that skin cells are proliferated, the increase of reactive oxygen species in skin cells is remarkably suppressed, and cell death induced by H 2 O 2 and the like is suppressed.
본 발명의 상기 조성물은 피부보호 효과를 가지고 있어서, 화장품 또는 의약품의 용도로 사용될 수 있을 것이다. 본 발명에 따르는 조성물은 또한 조성물을 피부에 적용하였을 때 그의 분산을 용이하게 하기 위하여 조성물에 대한 희석제, 분산제 또는 담체로서 작용하는 화장품 또는 약제학적으로 허용가능한 비히클을 함유한다.The composition of the present invention has a skin-protecting effect and can be used for cosmetic or pharmaceutical use. The composition according to the present invention also contains a cosmetic or pharmaceutical acceptable vehicle that acts as a diluent, dispersant or carrier for the composition to facilitate its dispersion when applied to the skin.
물이 아닌 또는 물 이외의 비히클에는 액체 또는 고체 피부 연화제 (emollients), 용매, 보습제, 농조화제 (thickener) 및 분말이 포함될 수 있다. 화장품 또는 약제학적으로 허용가능한 비히클은 통상적으로 조성물의 중량을 기준으로 하여 5 내지 99.9%, 바람직하게는 25 내지 80%이며, 다른 화장품 또는 약제학적 보조제가 없는 경우에는 조성물의 나머지를 구성할 수 있다. 바람직하게는, 비히클은 비히클의 중량을 기준으로 하여 적어도 80 중량%가 물이다. 바람직하게는, 물은 본 발명의 조성물의 50 중량% 이상, 보다 바람직하게는 조성물의 중량을 기준으로 하여 60 내지 80 중량%를 차지한다.Non-aqueous or non-aqueous vehicles may include liquid or solid emollients, solvents, moisturizers, thickeners and powders. The cosmetically or pharmaceutically acceptable vehicle is typically 5 to 99.9%, preferably 25 to 80%, based on the weight of the composition, and may constitute the remainder of the composition in the absence of other cosmetic or pharmaceutical adjuvants . Preferably, the vehicle is water at least 80% by weight, based on the weight of the vehicle. Preferably, water comprises at least 50% by weight of the composition of the invention, more preferably 60 to 80% by weight of the composition.
주로 사용된 유화제의 평균 친수성-친유성 평형 (hydrophilic-lipophilic balance; HLB)에 따라 유중수 에멀젼 또는 수중 유 에멀젼을 제공하는 유화제와 함께 오일 또는 오일성 물질이 존재할 수도 있다.Depending on the average hydrophilic-lipophilic balance (HLB) of the predominantly used emulsifier, an oil or oily material may be present along with an emulsifier that provides a water-in-oil emulsion or an oil-in-water emulsion.
본 발명의 조성물은 바람직하게는 차광제 (sunscreens)를 함유한다. 차광제에는 자외선을 차단하기 위해 통상적으로 사용되는 물질이 포함된다. 화합물의 구체적인 예는 PABA의 유도체, 신나메이트 및 살리실레이트이다.The composition of the present invention preferably contains sunscreens. The light shielding agent includes a material conventionally used for shielding ultraviolet rays. Specific examples of the compound are derivatives of PABA, cinnamate and salicylate.
예를 들어, 옥틸메톡시신나메이트 및 2-하이드록시-4-메톡시벤조페논 (옥시벤존으로도 알려져 있음)이 사용될 수 있다. 옥틸메톡시신나메이트 및 2-하이드록시-4-메톡시벤조페논은 각각 상품명 파르솔 (Parsol) MCX 및 벤조페논-3 (Benzophenone-3)으로 시판되는 것을 이용할 수 있다. 에멀젼에서 사용되는 차광제의 정확한 양은 태양의 UV 조사에 대해 원하는 방어도에 따라 달라질 수 있다.For example, octyl methoxycinnamate and 2-hydroxy-4-methoxybenzophenone (also known as oxybenzone) can be used. Octylmethoxycinnamate and 2-hydroxy-4-methoxybenzophenone, which are commercially available under the trade names Parsol MCX and Benzophenone-3, respectively, can be used. The exact amount of light-shielding agent used in the emulsion may vary depending on the desired degree of protection for the UV irradiation of the sun.
본 발명이 화장료 조성물로 사용되는 경우, 그 화장품 조성물 내에는 피부 연화제가 종종 혼입된다. 이러한 피부 연화제의 레벨은 전체 조성물의 중량을 기준으로 하여 0.5 내지 50%, 바람직하게는 5 내지 30%의 범위일 수 있다. 피부 연화제는 에스테르, 지방산 및 지방 알콜, 폴리올 및 탄화수소와 같은 일반적인 화학적 카테고리로 분류될 수 있다.When the present invention is used as a cosmetic composition, an emollient is frequently incorporated into the cosmetic composition. The level of such emollient may range from 0.5 to 50%, preferably from 5 to 30%, based on the weight of the total composition. Emollients can be classified into general chemical categories such as esters, fatty acids and fatty alcohols, polyols and hydrocarbons.
에스테르는 모노- 또는 디-에스테르일 수 있다. 허용가능한 지방산 디-에스테르의 예에는 디부틸아디페이트, 디에틸세바케이트, 디이소프로필다이머레이트 및 디옥틸숙시네이트가 포함된다. 허용가능한 측쇄 지방산 에스테르에는 2-에틸-헥실미리스테이트, 이소프로필스테아레이트 및 이소스테아릴팔미테이트가 포함된다. 허용가능한 3염기산 에스테르에는 트리이소프로필트리리놀리에이트 및 트리라우릴시트레이트가 포함된다. 허용가능한 직쇄 지방산 에스테르에는 라우릴팔미테이트, 미리스틸락테이트 및 스테아릴올리에이트가 포함된다. 바람직한 에스테르에는 코코-카프릴레이트/카프레이트(코코-카프릴레이트와 코코-카프레이트의 배합물), 프로필렌글리콜 미리스틸에테르아세테이트, 디이소프로필아디페이트 및 세틸옥타노에이트가 포함된다.The esters may be mono- or di-esters. Examples of acceptable fatty acid di-esters include dibutyl adipate, diethyl sebacate, diisopropyl dimerate and dioctyl succinate. Acceptable branched chain fatty acid esters include 2-ethyl-hexyl myristate, isopropyl stearate, and isostearyl palmitate. Acceptable tribasic acid esters include triisopropyltrinolinate and triarylsitrate. Acceptable straight chain fatty acid esters include lauryl palmitate, myristyl lactate and stearyl oleate. Preferred esters include coco-caprylate / caprate (a combination of coco-caprylate and coco-caprate), propylene glycol myristyl ether acetate, diisopropyl adipate, and cetyl octanoate.
적절한 지방 알콜 및 지방산에는 10 내지 20개의 탄소 원자를 갖는 화합물이 포함된다. 특히 바람직한 것은 세틸, 미리스틸, 팔미틸 및 스테아릴 알콜 및 산과 같은 화합물이다.Suitable fatty alcohols and fatty acids include compounds having from 10 to 20 carbon atoms. Particularly preferred are compounds such as cetyl, myristyl, palmityl and stearyl alcohols and acids.
피부 연화제로 작용할 수 있는 폴리올중에는 직쇄 및 측쇄 알킬폴리하이드록실 화합물이 있다. 예를 들어, 프로필렌글리콜, 소르비톨 및 글리세린이 바람직하다. 또한, 폴리-프로필렌글리콜 및 폴리에틸렌글리콜과 같은 중합체 폴리올이 유용하게 사용될 수 있다. 부틸렌 및 프로필렌 글리콜은 또한 침투 증진제로서 특히 바람직하다.Among the polyols that can act as emollients are straight chain and branched chain alkyl polyhydroxyl compounds. For example, propylene glycol, sorbitol and glycerin are preferred. In addition, polymer polyols such as poly-propylene glycol and polyethylene glycol may be usefully employed. Butylene and propylene glycol are also particularly preferred as penetration enhancers.
피부 연화제로서 작용할 수 있는 탄화수소의 예로는 어떤 경우든 12 내지 30개의 탄소 원자를 갖는 탄화수소 사슬을 갖는 것이다. 구체적인 예로는 광유, 와셀린 (petroleum jelly), 스쿠알렌 및 이소파라핀이 포함된다.Examples of hydrocarbons which can act as emollients are in any case those having a hydrocarbon chain having 12 to 30 carbon atoms. Specific examples include mineral oil, petroleum jelly, squalene and isoparaffin.
본 발명의 조성물이 화장품의 용도로 사용되는 경우에는 조성물 내의 또다른 카테고리의 기능성 성분은 농조화제이다. 농조화제는 어떤 경우든지 통상으로는 조성물의 중량을 기준으로 0.1 내지 20%, 바람직하게는 약 0.5 내지 10%의 양으로 존재한다. 농조화제의 예는 비.에프.구드리치 컴퍼니 (B.F. Goodrich Company)로부터 상품명 카보폴 (Carbopol)로 시판되는 가교된 폴리아크릴레이트 물질이다. 크산탄, 카라기닌, 젤라틴, 카라야, 펙틴 및 로커스트빈 (locust bean) 고무와 같은 고무가 사용될 수도 있다. 특정한 환경하에서 농조화 기능은 실리콘 또는 피부 연화제로서 작용하기도 하는 물질에 의해 제공될 수도 있다. 예를 들어, 10 센티스토크 이상인 실리콘고무 및 글리세롤스테아레이트와 같은 에스테르는 이중적인 기능성을 갖는다.When the composition of the present invention is used for cosmetic use, another category of functional ingredient in the composition is a thickening agent. The thickening agent is in any case usually present in an amount of from 0.1 to 20%, preferably from about 0.5 to 10%, based on the weight of the composition. An example of a thickener is a cross-linked polyacrylate material available from B. F. Goodrich Company under the trade name Carbopol. Rubber such as xanthan, carrageenin, gelatin, karaya, pectin and locust bean rubber may also be used. Under certain circumstances, the thickening function may also be provided by a substance that also acts as a silicone or emollient. For example, esters such as silicone rubber and glycerol stearate, which are greater than 10 centistokes, have dual functionality.
분말이 본 발명의 화장품 조성물내에 혼입될 수도 있다. 이들 분말에는 초크 (chalk), 탈크, 카올린, 전분, 스멕타이트(smectite) 점토, 화학적으로 변형된 마그네슘 알루미늄 실리케이트, 유기적으로 변형된 몬모릴로나이트 점토, 수화된 알루미늄 실리케이트, 훈증 실리카, 알루미늄 전분 옥테닐숙시네이트 및 이들의 혼합물이 포함된다.Powders may also be incorporated into the cosmetic compositions of the present invention. These powders include, but are not limited to, chalk, talc, kaolin, starch, smectite clay, chemically modified magnesium aluminum silicate, organically modified montmorillonite clay, hydrated aluminum silicate, fumed silica, aluminum starch octenyl succinate, Mixtures thereof.
그 밖의 다른 보조적인 미량 성분이 또한 본 발명의 화장품 조성물 내에 혼입될 수 있다. 이들 성분에는 착색제, 유백화제 및 향료가 포함될 수 있다. 이들 다른 보조적 미량 성분의 양은 어떤 경우든 조성물의 중량을 기준으로 0.001 내지 20% 까지의 범위일 수 있다.Other auxiliary minor components may also be incorporated into the cosmetic compositions of the present invention. These ingredients may include coloring agents, milifying agents, and perfumes. The amount of these other auxiliary minor components may in any case be in the range of from 0.001 to 20% based on the weight of the composition.
본 발명에 따르는 조성물은 일차적으로 사람의 피부에 국소 적용하기 위한 제품, 특히 피부의 컨디쇼닝, 보습(moisturizing) 및 유연화(smoothening), 피부의 두께, 유연성 및 탄력성의 증가, 및 주름살이 있거나, 주름지거나 노화된 피부의 출현의 방지 또는 감소를 위한 제제로서 사용된다.The composition according to the invention is primarily intended for topical application to human skin, in particular for conditioning, moisturizing and smoothening the skin, increasing the thickness, flexibility and elasticity of the skin, Or as an agent for preventing or reducing the appearance of aged or aged skin.
사용시에는 소량, 예를 들어 1 내지 100 ㎖의 조성물을 적절한 용기 또는 도포기(applicator)를 이용하여 피부의 노출된 면적에 적용하고, 필요에 따라, 그 후에 손 또는 손가락 또는 적절한 기구를 사용하여 피부에 펴바르고(거나) 문지른다.In use, a small amount of, for example, 1 to 100 ml of the composition is applied to the exposed area of the skin using an appropriate container or applicator and, if necessary, And then rubbed or rubbed.
본 발명의 국소적 피부 보호 조성물은 로숀, 크림 또는 겔로서 제제화될 수 있다. 조성물은 그의 점도 및 소비자가 목적하는 용도에 맞는 적절한 용기로 포장될 수 있다. 예를 들어, 로숀 또는 크림은 병 또는 롤-볼 (roll-ball) 도포기, 또는 추진제-구동된 에어로졸 장치 또는 손가락 가동에 적절한 펌프가 장착된 용기내에 포장될 수 있다. 조성물이 크림인 경우에, 이것은 간단히 비-변형성 병 또는 스퀴즈 (squeeze) 용기, 예를 들어 튜브 또는 뚜껑이 있는 자아 (jar) 또는 캡슐 내에 저장될 수 있다.The topical skin protective composition of the present invention may be formulated as a lotion, cream or gel. The composition may be packaged in a suitable container for its viscosity and intended use by the consumer. For example, the lotion or cream may be packaged in a bottle or roll-ball applicator, or in a propellant-driven aerosol device or in a container equipped with a pump suitable for finger operation. If the composition is a cream, it may simply be stored in a non-deformable bottle or squeeze container, for example a jar or capsule with a tube or lid.
본 발명의 실험 결과, 다음과 같은 내용을 확인하였다.As a result of the experiment of the present invention, the following contents were confirmed.
1. 멜라토닌과 코티솔 농도가 높아짐에 따라 세포 독성이 나타남을 확인하였다.1. It was confirmed that cytotoxicity was observed as the concentration of melatonin and cortisol increased.
2. 멜라토닌의 1회 처리와 UV 1회 조사에서는 세포 손상을 막지 못하였다.2. Treatment of melatonin and UV irradiation did not prevent cell damage.
3. 0.03% H2O2 노출에서도 전처리에 따른 세포 속상을 막지 못하였다.3. Even after exposure to 0.03% H 2 O 2 , the cells were not blocked by pretreatment.
4. 멜라토닌은 항산화제로 효과적인 것을 확인하였다. (UV 조사 실험에서 양성 대조군 참고, H2O2 노출에서 양성 대조군 참고).4. Melatonin was found to be effective as an antioxidant. (See positive control in UV irradiation experiments, positive control in H 2 O 2 exposure).
5. 멜라토닌 10 혹은 100 μM 주기적인 사용시, 대조군에 비해 회복 속도가 빨라지는 것을 확인하였다 (도 9~10 및 표 6~7 참고).5. When
6. UV-B 같은 경우, 높은 선량에 주기적으로 노출시 세포 손상이 심각한 것을 확인하였다 (양성 대조군 또한 주기적인 노출에 세포 손상이 높아지는 현상이 나타남).6. In the case of UV-B, periodic exposure to high doses indicated that the cell damage was severe (positive control also exhibited increased cellular damage during periodic exposure).
7. 멜라토닌의 주기적인 처리는 손상받은 세포의 회복을 빠르게 하는데 도움을 준다고 판단된다 (표 6~7 참고).7. Periodic treatment of melatonin appears to help speed up recovery of damaged cells (see Tables 6-7).
상기와 같이 구성되는 본 발명에 따른 피부 보호용 조성물은 항산화 효과가 뛰어날 뿐만 아니라 UV-A 및 B와 H2O2와 화학물질로부터 피부 손상을 막아줌으로 피부보호가 뛰어나다.The composition for skin protection according to the present invention is excellent in antioxidative effect and also has excellent skin protection by preventing skin damage from UV-A and B, H 2 O 2 and chemical substances.
도 1은 멜라토닌 농도에 따른 세포 독성 변화를 나타낸 그래프이다.
도 2는 코티솔 농도에 따른 세포 독성 변화를 나타낸 그래프이다.
도 3은 멜라토닌의 용매에 따른 세포 독성 변화를 나타낸 그래프이다.
도 4는 화학적 손상에 의한 세포 독성 변화를 나타낸 그래프이고, 이때 약물 (멜라토닌과 코티솔) 전처리 후 (12시간) 0.03% H2O2 외부자극 유도 물질을 처리한 것이다.
도 5는 UV-조사 시스템의 형태에 대한 사진이고, 이때 (좌) UV-off 상태, (우) UV-on 상태이다.
도 6은 자외선 (UV-A)에 의한 세포 독성 및 멜라토닌의 효과를 관찰한 그래프이다.
도 7은 자외선 (UV-B)에 의한 세포 독성 및 멜라토닌의 효과를 관찰한 그래프이다.
도 8은 주기적인 UV-A 조사 및 멜라토닌 처리를 통한 세포 변화를 관찰한 그래프이다.
도 9는 주기적인 UV-B 조사 및 멜라토닌 처리를 통한 세포 변화를 관찰한 그래프이다.
도 10은 UV-B 조사시 3일 동안의 세포 변화를 관찰한 그래프이다.
도 11은 UV 콘트롤 박스(Control box)의 실물 사진이다.
도 12는 UV 측정 장치의 실물 사진이다.
도 13은 UV 램프의 실물 사진이다.
도 14는 본원발명에 사용된 비타민 C, 멜라토닌, 피크노제놀의 결합 형태를 나타낸 전자현미경 사진이다.1 is a graph showing changes in cytotoxicity with respect to melatonin concentration.
2 is a graph showing changes in cytotoxicity with cortisol concentration.
FIG. 3 is a graph showing changes in cytotoxicity depending on the solvent of melatonin. FIG.
FIG. 4 is a graph showing changes in cytotoxicity due to chemical damage, in which 0.03% H 2 O 2 external stimulus inducing substance was treated after pretreatment of the drug (melatonin and cortisol) (12 hours).
5 is a photograph of the shape of the UV-irradiation system, in this case (left) UV-off state and (right) UV-on state.
6 is a graph showing cytotoxicity and effect of melatonin by ultraviolet (UV-A).
7 is a graph showing cytotoxicity and effect of melatonin by ultraviolet (UV-B).
8 is a graph showing cell changes observed through periodic UV-A irradiation and melatonin treatment.
FIG. 9 is a graph showing cell changes observed through periodic UV-B irradiation and melatonin treatment. FIG.
10 is a graph showing cell changes during UV-B irradiation for 3 days.
11 is a photograph of a UV control box.
Fig. 12 is a photographic image of a UV measuring device.
13 is a photographic view of a UV lamp.
FIG. 14 is an electron micrograph showing the binding form of vitamin C, melatonin, and pycnogenol used in the present invention.
이하, 본 발명에 따른 바람직한 실시예를 더욱 구체적으로 제시하여 상세하게 설명하기로 한다. 그러나, 이하의 실시예는 이 기술분야에서 통상적인 지식을 가진 자에게 본 발명이 충분히 이해되도록 제공되는 것으로서 여러 가지 다른 형태로 변형될 수 있으며, 이와 같은 실시예들에 의하여 본 발명이 한정되는 것은 아니다.Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the drawings. However, it should be understood that the following embodiments are provided so that those skilled in the art may understand the present invention without departing from the scope and spirit of the present invention. no.
<실시예 1> 실험 준비≪ Example 1 >
<1-1> UV 조사 시스템 구성<1-1> Configuration of UV irradiation system
1) UV-A 및 B 램프, 2) 콘트롤 박스, UV 탐지기로 구성된다.1) UV-A and B lamps, 2) control box, and UV detector.
UV 실험에 사용된 장비는 다음과 같다. 먼저, 실제 UV 콘트롤 박스(Control box)는 도 11과 같다. 콘트롤 박스에서는 UV 램프와 직접 연결을 하여, 시간을 조절할 수 있다. 구체적으로, 1초부터 59분 59초까지 시간 조절이 가능하며 설정한 타이머 시간이 다 되면 자동적으로 램프의 전원을 차단하였다.The equipment used in the UV test is as follows. First, the actual UV control box is shown in FIG. In the control box, you can connect the UV lamp directly and adjust the time. Specifically, the time can be adjusted from 1 second to 59 minutes and 59 seconds, and the lamp power is automatically turned off when the set timer time expires.
UV 측정 장치의 특징 및 사양은 다음과 같다. 본 실험을 시작하기 전 항상 램프의 강도를 도 12의 장치를 이용하여 측정을 한 뒤에 실험을 진행하였다.The features and specifications of the UV measuring device are as follows. Before starting the experiment, the intensity of the lamp was always measured using the apparatus of FIG.
UV 측정 장치의 제원은 하기 표 1과 같다.The specifications of the UV measuring device are shown in Table 1 below.
UV 램프의 실물 사진은 도 13과 같다. UV 램프는 필립스 제품을 사용하였고 A 램프의 특징은 315~380 nm 파장 범주이고 350 nm 방출 피크를 나타낸다. B 램프의 경우는 305 ~ 315 nm 파장 범주이고 311 nm에서 방출 피크를 나타낸다.The actual photograph of the UV lamp is shown in Fig. The UV lamp uses a Philips product and the characteristics of the A lamp are a wavelength range of 315 to 380 nm and a 350 nm emission peak. In the case of the B lamp, it is in the wavelength range of 305 to 315 nm and shows the emission peak at 311 nm.
UV 조사 조건은 다음과 같다.The UV irradiation conditions are as follows.
Philips 램프를 이용하였고, 스탠드의 높낮이를 통해 강도를 조절할 수 있게 준비하였다 (UV-A: 9W, 315~380 nm 파장, 350 nm 최대 방출; UV-B: 9W, 305~315 nm 파장, 311 nm 최대 방출). 콘트롤 박스에서는 시간을 조절하여 자동으로 꺼지게 하였다. 기상청 보도 자료에 따르면 대한민국 5~7월 달에는 UV-A가 최대 5J(8시간 노출이 된다고 가정), 6~9월 달에는 UV-B가 최대 70mJ (A와 마찬가지로 8시간 노출이 된다고 가정)으로 노출이 된다고 한다. 실험시 약물의 영향을 줄이기 위해 약물과 배지를 제거하고 PBS로 채운 후 UV를 조사하였다. 실험 전 UV-meter (길우 트레이딩, 서울, 대한민국) 측정을 통하여 UV-A는 1.7 mW/㎠으로 50 분간 (5.1 J) 조사하였고, UV-B 같은 경우는 0.38 mW/㎠으로 30분간 (70 mJ) 조사하였다.(UV-A: 9W, wavelength from 315 to 380 nm, 350 nm maximum emission; UV-B: 9 W, wavelengths from 305 to 315 nm, 311 nm) using a Philips lamp and adjusting the height of the stand Maximum emission). In the control box, the time was adjusted to automatically turn off. According to the Meteorological Agency press release, UV-A is max 5J (assumes 8 hour exposure) in May-July of Korea and UV-B is 70mJ in month of June-September . To reduce the effect of the drug during the experiment, the drug and media were removed, filled with PBS, and irradiated with UV light. UV-A was irradiated for 50 min (5.1 J) at 1.7 mW / cm 2 through a UV-meter (Gil Woo Trading, Seoul, Korea) before the experiment and 0.38 mW / Respectively.
<1-2> 시약 및 기기<1-2> Reagents and devices
세포배양용 기본 배지와 성분 (media, FBS 등.), 생존도 분석키트(Viability assay kit) (Ez-cytox), Elisa kit (ROS 분석에 사용), IHC 항체 (세포 기능 관련 분석), 시약 (멜라토닌, 코티솔 등.), 지방선구세포(Pre-adipocyte) 분화 시약 등을 이용하였다.Cell culture media and media (eg, FBS), viability assay kit (Ez-cytox), Elisa kit (used for ROS analysis), IHC antibody (cell function analysis) Melatonin, cortisol, etc.), and pre-adipocyte differentiation reagents.
이때, 코티솔(Cortisol), 멜라토닌(melatonin), 피크노제놀, 비타민 C는 sigma (St. Lous, MO, USA)에서, Ez-cytoc는 대일랩(서울, 대한민국)에서 구입하였고, 액체 시약들은 18.2 MΩ·cm 으로 증류된 증류수로 제작하였다. Cortisol, melatonin, pycnogenol and vitamin C were purchased from sigma (St. Lous, MO, USA) and Ez-cytoc were purchased from Daeil Lab (Seoul, Korea) cm < / RTI > of distilled water.
<실시예 2> 세포 준비와 배양 및 시약 처리≪ Example 2 > Cell preparation, culture and reagent treatment
HaCat (성인 인간 피부로부터 자연적으로 형질전환된 이수성 불멸의 케라티노사이트 세포주(a spontaneously transformed aneuploidy immortal keratinocyte cell line from adult human skin); Human adult keratinocyte) 세포를 10% FBS(fetal bovine serum), 1% 페니실린 및 1% 스트렙토마이신이 혼합된 DMEM(Dulbecco's modified Eagle's medium) 배지에서 배양하였다. 세포들은 37℃ 배양기에서 95% CO2 농도 환경에서 배양하고 이틀에 한번씩 배양액을 교체하였다. 세포를 계대배양 할 때에는 0.25% 트립신을 이용하여 세포를 단일 세포로 만들었다. 96 웰플레이트(well plate)에 1X104 세포 농도로 넣고 24시간 지난 후 세포가 이상없이 부착된 것을 확인을 한 후 멜라토닌과 코티솔을 처리하였다.Human adult keratinocyte cells were cultured in 10% fetal bovine serum (FBS), 1% fetal bovine serum (FBS), and 10% fetal bovine serum Penicillin and 1% streptomycin in DMEM (Dulbecco's modified Eagle's medium) medium. The cells were cultured in a 95% CO 2 -concentrated environment at 37 ° C, and the culture medium was changed every other day. Cells were subcultured using 0.25% trypsin. After incubation for 24 hours at a concentration of 1 × 10 4 cells in a 96-well plate, the cells were observed to have adhered without any abnormality and treated with melatonin and cortisol.
<2-1> 세포 활성도 실험<2-1> Cell activity experiment
상기와 같이 1X104 cell/well 세포 농도로 배양 후, 약물 처리 및 UV 조사를 끝낸 세포들을 다시 37℃ 인큐베이터에 배양을 하여 24시간 후에 Ez-cytox 시약을 이용하여 세포의 생존율을 관찰하였다. 이때 약물과 UV 처리하지 않는 군을 정상군으로 판단하여 기준점으로 하였다.After culturing at 1 × 10 4 cells / well as described above, the cells treated with the drug and UV were cultured again in a 37 ° C. incubator. Cell viability was observed using Ez-cytox reagent after 24 hours. At this time, the drug and the group not treated with UV were regarded as the normal group and set as the reference point.
<2-1> 세포 증식 실험<2-1> Cell proliferation experiment
4X104 cell/well 세포 농도로 배양 후 약물 처리 (12시간) 및 UV를 조사하였다. 이때 다시 인큐베이터에서 배양 후 다시 약물 처리 및 UV 조사하였다. 이와 같은 방법으로 4~5일을 반복하여 UV에 노출 및 약물을 처리하여 대조군에 비해 약물 투여군에서 회복 정도를 관찰하였다.After culturing at 4 × 10 4 cell / well cell concentration, drug treatment (12 hours) and UV irradiation were performed. At this time, the cells were cultured again in an incubator, and then drug treatment and UV irradiation were performed again. In the same manner, exposure to UV and drug treatment were repeated for 4 to 5 days, and the degree of recovery was observed in the drug administration group compared to the control group.
<실시예 3> 약물의 세포독성 실험<Example 3> Cytotoxicity test of drug
<3-1> 멜라토닌과 코티솔의 세포 독성 평가<3-1> Evaluation of cytotoxicity of melatonin and cortisol
멜라토닌 농도에 따른 세포 독성 변화와 코티솔 농도에 따른 세포 독성 변화를 관찰하였다(도 1 및 도 2). 구체적으로, 도 1 및 도 2에 기재된 농도의 변화로 멜라토닌과 코티솔을 HaCat 세포에 처리한 결과, 멜라토닌과 코티솔의 농도가 높아짐에 따라 세포 독성이 있음을 확인하였다.Changes in cytotoxicity due to melatonin concentration and changes in cytotoxicity according to cortisol concentration were observed (FIGS. 1 and 2). Specifically, melatonin and cortisol were treated with HaCat cells by the changes of the concentrations shown in FIG. 1 and FIG. 2, and it was confirmed that they were cytotoxic as the concentrations of melatonin and cortisol were increased.
멜라토닌과 코티솔의 농도에 따른 세포 독성 평가는 하기 표 2와 같다.The cytotoxicity according to the concentration of melatonin and cortisol is shown in Table 2 below.
그 결과, UV 조사를 통한 세포 보호 효과를 보기 전, 약물의 독성을 평가하였다. 상기 도 1 및 2와 표 2에서 보는 것과 같이 두 약물 (멜라토닌과 코티솔)에서 500ㅅM 이상 가면 세포 독성이 강하게 나타나는 것을 확인하였다 (72.54% 및 70.98%). 그리고 멜라토닌의 경우 100 ㅅM 이상이 되는 농도에서는 통계학적인 차이를 보였다. 멜라토닌은 물에서는 0.1mg/ml로 상대적으로 용해성이 낮다. 하지만 DMSO와 같은 유기 용매에서는 11.6 mg/ml로 농도를 높일 수 있다.As a result, the toxicity of the drug was evaluated before the cytoprotective effect by UV irradiation was observed. As shown in FIGS. 1 and 2 and Table 2 above, it was confirmed that the cytotoxicity of the two drugs (melatonin and cortisol) was more than 500 mS (72.54% and 70.98%). In the case of melatonin, there was a statistical difference at the concentration of 100 M M or more. Melatonin is relatively low in solubility at 0.1 mg / ml in water. However, in organic solvents such as DMSO, the concentration can be increased to 11.6 mg / ml.
즉, 멜라토닌, 코티솔의 농도에 따른 세포 독성을 확인하고, 농도가 높아짐에 따라 세포 독성이 나타남을 확인하였다.In other words, cytotoxicity of melatonin and cortisol was observed, and cytotoxicity was observed as concentration increased.
<3-2> 용매에 따른 멜라토닌의 독성<3-2> Toxicity of Melatonin by Solvent
멜라토닌의 용매에 따른 HaCat 세포 독성 변화를 관찰하였다(도 3). 그 결과, 멜라토닌을 녹이는 용매 (DMSO와 배지)에 따라 농도 차이가 있음을 확인하였다. 그러나, DMSO 유기 용매는 일반 배지에 비하여 그 자체의 독성으로 인해 세포 독성이 발생할 수 있으나, DMSO 용매에서도 고농도로 제작 가능함을 확인하였다.The change in HaCat cytotoxicity according to the solvent of melatonin was observed (Fig. 3). As a result, it was confirmed that there was a difference in concentration depending on the solvent for dissolving melatonin (DMSO and medium). However, the DMSO organic solvent has cytotoxicity due to its toxicity compared to the general medium, but it is confirmed that DMSO solvent can be produced at a high concentration also in DMSO solvent.
멜라토닌을 녹이는 용질에 따른 독성 차이가 있는지 알아보기 위해 다음과 같은 추가 실험을 진행하였다. 용매에 따른 멜라토닌의 독성 평가는 하기 표 3과 같다(단위: %).The following additional tests were conducted to determine if there is any toxicity difference depending on the solute melting melatonin. The evaluation of the toxicity of melatonin according to the solvent is shown in Table 3 (unit:%).
구체적으로, DMSO에 녹인 멜라토닌은 100 ㅅM에서부터 세포 독성이 나타나는 반면, 배지(media) 처리시에는 200 μM에서부터 세포 독성이 나타났다. 한편, 코티솔은 2가지 용매 모두 100 μM 이상부터 세포 독성이 나타났다. Specifically, melatonin dissolved in DMSO showed cytotoxicity from 100 μM, while cytotoxicity was observed from media up to 200 μM. On the other hand, cortisol showed cytotoxicity from 100 μM or more in both solvents.
상기에서 설명한 것처럼 멜라토닌은 물에는 낮은 농도로 녹는 물질로 알려져 있다. 따라서, 그 농도를 높이기 위해서 DMSO와 같은 유기용매를 사용하였다. 하지만 이러한 유기용매는 세포나 조직에 매우 안 좋은 영향을 미칠 수 있기 때문에 용해도가 상대적으로는 낮지만 안정적인 용매에 녹인 멜라토닌을 비교해 보았다(그 결과는 도 3과 표 3). 같은 농도 일지라도 배지에 녹인 멜라토닌이 상대적으로 세포 독성이 낮았다. 뿐만 아니라 멜라토닌은 DMSO와 같은 유기용매에 더 잘 녹일 수 있었지만, 세포 독성이 증가하여 고농도로는 처리를 할 수가 없었다 (100 ㅅM 이상시 통계학적 차이를 보임). 하지만 배지에 녹인 멜라토닌의 경우 100 ㅅM 농도에서도 세포 독성이 없는 것을 확인하였다. As described above, melatonin is known as a substance that melts in water at low concentrations. Therefore, an organic solvent such as DMSO was used to increase the concentration. However, since these organic solvents may have a very bad influence on the cells or tissues, the melatonin dissolved in a stable solvent is compared with a comparatively low solubility (the results are shown in FIG. 3 and Table 3). Even at the same concentration, the melatonin dissolved in the medium was relatively low in cytotoxicity. In addition, melatonin was more soluble in organic solvents such as DMSO, but increased cytotoxicity and could not be treated at high concentrations (statistical differences above 100 M). However, it was confirmed that melatonin dissolved in the medium had no cytotoxicity even at 100 μM concentration.
이에, 본 실험에서는 UV 조사에 사용되는 멜라토닌은 배지에 녹인 것을 이용하여 세포 독성을 최대한으로 낮춘 것으로 세포에 처리하였다.Therefore, in this experiment, melatonin used for UV irradiation was treated with cells dissolved in a medium to minimize cytotoxicity.
<실시예 4> 화학적 손상에 의한 세포 독성 및 멜라토닌의 효과 Example 4 Cytotoxicity and Effect of Melatonin by Chemical Damage
세포가 화학적 물질에 노출되었을 때의 세포 손상 정도를 확인하였다. 구체적으로, 화학적 손상을 위한 화학적 물질로 H2O2를 준비하고, 최종 농도 0.03% H2O2 처리를 통하여 HaCat 세포 독성을 유도하였다. 구체적으로, 12시간 전에 약물(멜라토닌과 코티)을 전처리한 후, 0.03% H2O2 외부자극 유도 물질을 처리하였다. 양성 대조군은 멜라토닌 100 μM을 사용하였다(도 4). 이때, 상기 도면에서 M1, M10, M100, C1, C10, C100은 각각 멜라토닌 1 μM, 10 μM, 100 μM 처리와 코티솔 1 μM, 10 μM, 100 μM 처리를 나타낸다. 이하 실험도 동일하다.The degree of cell damage when cells were exposed to chemical substances was confirmed. Specifically, H 2 O 2 was prepared as a chemical substance for chemical damage, and HaCat cell toxicity was induced through 0.03% H 2 O 2 treatment at a final concentration. Specifically, drugs (melatonin and cortisol) were pretreated 12 hours before treatment with 0.03% H 2 O 2 inducer. As a positive control, 100 μM of melatonin was used (FIG. 4). In the figure, M1, M10, M100, C1, C10 and C100 represent 1 μM, 10 μM and 100 μM melatonin treatment and 1 μM, 10 μM and 100 μM cortisol treatment, respectively. The following experiments are also the same.
그 결과, H2O2 노출시 양성 대조군으로 멜라토닌을 사용한 결과, 강한 항산화 효과가 나타남을 확인하였다.As a result, it was confirmed that a strong antioxidative effect was obtained when melatonin was used as a positive control at the time of exposure to H 2 O 2 .
<실시예 5> UV 조사에 따른 세포 독성 실험<Example 5> Cytotoxicity test by UV irradiation
세포가 UV에 조사될 때의 손상을 실험하기 위하여, UV-조사 시스템을 준비하였다(도 5). 상기 도 5는 실제 실험을 들어가기 전과 시작한 사진을 보여주는 사진이다. UV 측정기(도 12)를 이용하여 플레이트를 통과하는 UV 양을 측정하여 세포에 조사하였다. 이때 조사 시간은 콘트롤 박스(도 11)에 설정하여 진행하였다.To test the damage when the cells were irradiated with UV, a UV-irradiation system was prepared (Figure 5). FIG. 5 is a photograph showing the photographs before and after the actual experiment. The amount of UV through the plate was measured using a UV detector (Fig. 12) and irradiated to the cells. At this time, the irradiation time was set in the control box (FIG. 11).
상기 UV는 2가지 상태로 설정하였다. 구체적으로, 1) UV-A는 5~7월 달에 UV-A가 최대 강도로 8시간 노출이 되었다고 가정하였고, 2) UV-B는 6~9월 달에 UV-B가 최대 강도로 8시간 노출이 되었다고 가정하였다.The UV was set in two states. Specifically, 1) UV-A was assumed to be exposed for 8 hours at the maximum intensity of UV-A in the month of May to July, and 2) UV-B was irradiated with UV- Time exposure was assumed.
UV-A는 5J 조사에 따른 멜라토닌 약물의 효과를 관찰하였다(도 6). 또한, UV-B 70mJ 조사에 따른 멜라토닌 약물의 효과를 관찰하였다(도 7). 이때, 양성 대조군은 멜라토닌 100 μM을 사용하였다.UV-A observed the effect of melatonin drug on 5J irradiation (Fig. 6). In addition, the effect of the melatonin drug upon UV-B 70 mJ irradiation was observed (FIG. 7). At this time, 100 μM of melatonin was used as a positive control.
그 결과, UV 조사시 양성 대조군으로 멜라토닌을 사용한 결과, 강한 항산화 효과를 나타남을 확인하였으나, 1회 멜라토닌 혹은 코티솔 처리는 UV 노출에 효과를 보이지 않았다.As a result, it was confirmed that when melatonin was used as a positive control in UV irradiation, it showed strong antioxidative effect. However, once melatonin or cortisol treatment did not show any effect on UV exposure.
하기 표 4는 UV-A 노출 전, 멜라토닌 처리에 따른 세포 독성 변화를 관찰한 것이다.Table 4 below shows changes in cytotoxicity following treatment with melatonin before UV-A exposure.
controlPositive
control
우리나라에서 UV-A 같은 경우 5~7월 달에 가장 강하게 노출되는 것으로 기상청에서 보고하였다. 이때 최대 5J(일일 8시간 노출이 된다는 가정)의 UV-A에 노출된다. UV-A에 노출이 되기 전 멜라토닌을 농도별로 처리한 후 UV-A에 노출시켰다. 양성 대조군은 UV 조사시 항산화 물질로 알려진 멜라토닌 100 ㅅM을 사용하였다. 그리고 멜라토닌 처리군은 1, 10, 100, 그리고 1000 ㅅM 농도로 처리하였다. 5J의 조사를 마친 뒤, 세포 독성을 관찰하였다. 이때 양성 대조군 만이 UV-A의 손상으로부터 효과적으로 보호하였을 뿐, 나머지 그룹들에서는 통계학적 유의성을 찾아보기 어려웠다.In Korea, the Korea Meteorological Agency reported that UV-A was most strongly exposed in May-July. At this time, it is exposed to UV-A of up to 5J (assuming exposure is 8 hours a day). Before exposure to UV-A, melatonin was treated by concentration and exposed to UV-A. In the positive control group,
하기 표 5는 UV-B 노출 전, 멜라토닌 처리에 따른 세포 독성 변화를 관찰한 것이다.Table 5 below shows changes in cytotoxicity due to melatonin treatment before UV-B exposure.
controlPositive
control
UV-B 같은 경우는 A에 비하여 세포 손상이 강한 것으로 알려졌다. 도 6과 7의 그래프를 통해 알 수 있듯이, UV-B 70 mJ에서 세포 독성이 대략 62.93% 나타나는 것을 확인하였다. A 때와 마찬가지로 멜라토닌과 양성 대조군을 이용하여 세포독성에 어떠한 영향을 미치는지를 확인해 본 결과, UV 조사시 멜라토닌의 처리는 보호 효과가 있음을 확인하였다 (도 7에서 대조군 vs 양성 대조군 비교, p<0.001). UV 조사 전 멜라토닌의 처리는 통계학적으로 유의성이 없었다.In the case of UV-B, it is known that cell damage is stronger than that of A. As can be seen from the graphs of FIGS. 6 and 7, it was confirmed that the cytotoxicity was approximately 62.93% at UV-B 70 mJ. A, melatonin and a positive control were used to examine the effect of melatonin on the cytotoxicity. As a result, it was confirmed that the treatment with melatonin had a protective effect upon UV irradiation (FIG. 7, comparison of control vs. positive control, p <0.001 ). Melatonin treatment before UV irradiation was not statistically significant.
<실시예 6> 자외선 (UV) 노출 및 멜라토닌의 주기적인 투여에 따른 회복 여부 ≪ Example 6 > Recovery from ultraviolet (UV) exposure and periodic administration of melatonin
실험 방법은 12시간 전에 약물 전처리한 후, UV를 조사한 후, 세포 독성을 관찰하였다.The experimental method was pretreatment of the
<6-1> UV-A의 주기적인 노출과 멜라토닌의 주기적인 처리에 따른 세포 회복<6-1> Regular exposure of UV-A and periodic treatment of melatonin
UV-A의 주기적인 노출과 멜라토닌의 주기적인 처리에 따른 세포 회복을 확인하였다(도 8). 선행 실험에서 UV-A는 5J, 및 B는 70mJ의 강도로 세포에 조사하였고, 1회 실험에서는 유의성을 발견할 수 없었다. 즉, 1회 약물 투여 및 1회 UV 조사 실험에서는 멜라토닌의 약물 효과가 구체적으로 확인이 되지 않았다.Periodic exposure of UV-A and cell recovery by periodic treatment of melatonin were confirmed (Figure 8). In preliminary experiments, UV-A was irradiated to the cells at 5 J, and B at 70 mJ, and no significance was found in the first experiment. That is, the drug effect of melatonin was not confirmed in the one-time drug administration and the one-time UV irradiation experiment.
주기적인 UV의 노출과 약물 처리에 따른 변화를 확인해 보기 위해 4일 연속 실험을 진행하였다 (조건: 약물 전처리 12시간 후 UV 노출 그리고 24시간 후 세포 독성 관찰의 반복). 주기적인 약물 처리와 UV 조사시에는 대조군에 비해 회복 속도가 빠른 것을 확인하였다. 하기 표 6은 주기적인 UV-A 조사 및 멜라토닌 처리에 따른 세포 변화를 관찰 결과를 기록한 것이다.The experiment was conducted for 4 consecutive days to check periodical UV exposure and changes due to drug treatment (condition: UV exposure after 12 hours of drug pretreatment and repeated cytotoxicity observation after 24 hours). Periodic drug treatment and UV irradiation showed faster recovery than the control group. Table 6 below shows the results of observation of periodic changes in cells upon irradiation with UV-A and with melatonin treatment.
controlPositive
control
아무런 처치도 하지 않고 UV-A 5J을 주기적으로 노출시키는 경우 정상군에 비해 상대적으로 세포 독성이 높게 나타나는 것을 확인하였다. UV 조사 동안 아무런 처치도 하지 않고 UV-A 5J을 주기적으로 노출시킬 경우 정상군에 비멜라토닌을 처리한 그룹에서는 상대적으로 독성이 낮아지는 것을 확인하였다. 약물 전처리한 그룹들에서도 시간이 지남에 따라 아무것도 처리하지 않은 그룹에 비해 회복 속도가 좋아지는 것을 확인하였다 (표 6). When UV-A 5J was exposed periodically without any treatment, it was confirmed that the cytotoxicity was relatively higher than that of the normal group. When UV-A 5J was exposed periodically without any treatment during UV irradiation, it was confirmed that the toxicity of the non-melatonin-treated group to the normal group was relatively low. In drug-pretreated groups, over time, recovery was found to be better than in the untreated group (Table 6).
<6-2> UV-B의 주기적인 노출과 멜라토닌의 주기적인 처리에 따른 세포 회복<6-2> Periodic exposure of UV-B and cell recovery by periodic treatment of melatonin
UV-B의 주기적인 노출과 멜라토닌의 주기적인 처리에 따른 세포 회복을 확인하였다(도 9). 또한, UV-B 조사시 3일 동안의 세포 변화를 관찰하였다(도 10). 하기 표 5는 주기적인 UV-B 조사 및 멜라토닌 처리에 따른 세포 변화를 관찰 결과를 기록한 것이다.Periodic exposure of UV-B and cell recovery by periodic treatment of melatonin were confirmed (Figure 9). In addition, cell changes during UV-B irradiation for 3 days were observed (FIG. 10). Table 5 below shows the results of observation of periodic changes in UV-B irradiation and cell changes due to the treatment with melatonin.
controlPositive
control
UV-B 같은 경우 A에 비해 세포 독성이 상대적으로 강한 것을 확인하였다. 반복적인 노출에도 세포 성장이 확인되는 A에 비해, B 같은 경우 세포들의 독성이 강해져 성장하지 못하고 죽어가는 것을 확인하였다. UV-B was found to be relatively more cytotoxic than A. In the case of B, the toxicity of the cells was stronger than that of A, in which cell growth was confirmed even after repeated exposure, and it was confirmed that the cells did not grow and died.
상기 실시예의 결과, UV-A 및 UV-B 모두 대조군 대비 보호 효과가 있음을 확인하였다. 다만, 70 mJ(UV-B)의 주기적인 노출은 72시간 이후에 모든 실험군에서 손상을 관찰하였다. 48시간 까지의 데이터를 보았을 때 멜라토닌 처리한 그룹이 대조군에 비해 상대적으로 회복이 빠름을 확인하였다.As a result of the above examples, it was confirmed that UV-A and UV-B had a protective effect against the control group. However, periodic exposure of 70 mJ (UV-B) was observed in all experimental groups after 72 hours. When the data up to 48 hours were examined, it was confirmed that the melatonin-treated group was relatively faster than the control group.
<실시예 7> 통계 분석≪ Example 7 > Statistical analysis
SPSS를 이용하여 각 실험 그룹들 간의 차이를 유의성 p<0.05 설정하여 비교하였다. 구체적으로, 데이터는 평균 ㅁ 표준편차 (SD)로 나타내었고, SPSS 소프트웨어 (version 22.0; SPSS Inc., IL, USA)를 사용한 크루스칼-왈리스 방법(kruskal-wallis)과 독립 t-테스트에 의해 분석하였다.Using SPSS, the difference between the experimental groups was determined by setting p <0.05. Specifically, the data were expressed as mean ㅁ standard deviation (SD) and were analyzed by the Kruskal-Wallis method using the SPSS software (version 22.0; SPSS Inc., IL, USA) Respectively.
<실시예 8> 멜라토닌, 피크노제놀 및 비타민 C 함유 피부보호용 조성물의 제조 및 실험Example 8 Preparation and Experiment of Skin Protective Composition Containing Melatonin, Pycnogenol and Vitamin C
하기 표 8에 기재한 바와 같은 성분의 피부보호용 조성물을 제조하였다. 구체적으로, 표 8에 나타낸 비율로 필수 성분에 해당하는 멜라토닌, 피크노제놀, 비타민C를 분말 상태로서 혼합한 후 혼합 믹서를 이용하여 10분간 잘 혼합하였다. 추가로 스테아르산 10mg, 유당 50mg 및 미결정상셀룰로오스 25mg을 더하여, 15분간 잘 혼합하여 조성물을 제조하였다.A skin protecting composition having the ingredients listed in Table 8 below was prepared. Concretely, melatonin, pycnogenol and vitamin C corresponding to essential ingredients were mixed in a powder state as shown in Table 8, and mixed well for 10 minutes using a mixing mixer. Further, 10 mg of stearic acid, 50 mg of lactose and 25 mg of pale normal cellulose were added and mixed well for 15 minutes to prepare a composition.
상기 조성물중 실시예 8-1로 제조된 물질을 전자현미경으로 확인한 결과, 도 14와 같은 구조를 형성하였다. 구체적으로, 내부에 비타민 C가 포함되고, 그 외부를 피크노제놀과 멜라토닌이 함께 둘러싼 형상, 즉, 멜라토닌과 피크노제놀이 함께 비타민 C를 코팅하는 구조를 나타내었다(도 14).As a result of confirming the material of Example 8-1 by electron microscope, the structure as shown in FIG. 14 was formed. Specifically, vitamin C was contained in the inside, and a form in which pycnogen and melatonin were enclosed together, that is, melatonin and pycnogenol co-coated with vitamin C (FIG. 14).
그리고, 상기 실시예 8-1, 8-2, 8-3의 조성물을 이용하여 상기 실시예 4의 화학적 손상에 의한 세포 독성 실험과, 실시예 5의 UV 조사에 따른 세포 독성 실험과 동일한 실험을 수행하였다.Using the compositions of Examples 8-1, 8-2, and 8-3, the same cytotoxicity experiment as in Example 4 above and the same experiment as the cytotoxicity experiment according to UV irradiation in Example 5 were performed Respectively.
그 결과, 멜라토닌 단독에 의한 실험에 비하여 실시예 8-1의 조성물은 화학적 손상의 경우 대략 3~5배, UV 조사에 따른 세포 독성의 경우는 5~10배 정도 그 효과가 높았다. 한편, 실시예 8-2의 조성물은 화학적 손상의 경우 대략 4~7배, UV 조사에 따른 세포 독성의 경우는 8~20배 정도 그 효과가 높았다. 그리고, 실시예 8-3의 조성물은 화학적 손상의 경우 대략 6~15배, UV 조사에 따른 세포 독성의 경우는 15~40배 정도 그 효과가 높았다.As a result, the composition of Example 8-1 was about 3 to 5 times in the case of chemical damage and 5 to 10 times in the case of cytotoxicity by UV irradiation, compared with the experiment by melatonin alone. On the other hand, the composition of Example 8-2 was about 4 to 7 times in the case of chemical damage and 8 to 20 times in the case of cytotoxicity by UV irradiation. The composition of Example 8-3 was about 6 to 15 times in the case of chemical damage and about 15 to 40 times in the case of cytotoxicity by UV irradiation.
이상, 본 발명의 바람직한 실시예를 들어 상세하게 설명하였으나, 본 발명은 상기 실시예에 한정되는 것은 아니며, 본 발명의 기술적 사상의 범위내에서 당 분야에서 통상의 지식을 가진 자에 의하여 여러 가지 변형이 가능하다.While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, This is possible.
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| KR102439976B1 (en) * | 2021-09-13 | 2022-09-06 | (주)닥터솔루션 | Natural antioxidant antibacterial cosmetic composition containing Shinyang cherry tree fruit extract and melatonin, which are natural antioxidants |
| KR102488079B1 (en) * | 2021-08-02 | 2023-01-17 | 주식회사 참존 | Cosmetic composition containing the extracts complex of Prunus Cerasus, Beta Vulgaris, Lentinus Edodes and Tricholoma Matsutake |
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| KR20090126785A (en) * | 2008-06-05 | 2009-12-09 | 홉킨스바이오연구센터(주) | Antioxidant Complex Composition Containing Pycnogenol, Resveratrol and Antioxidant Vitamins |
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| KR102488079B1 (en) * | 2021-08-02 | 2023-01-17 | 주식회사 참존 | Cosmetic composition containing the extracts complex of Prunus Cerasus, Beta Vulgaris, Lentinus Edodes and Tricholoma Matsutake |
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