KR102469725B1 - Composition for improving skin aging containing Vaccinium uliginosum powder - Google Patents
Composition for improving skin aging containing Vaccinium uliginosum powder Download PDFInfo
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- KR102469725B1 KR102469725B1 KR1020200074034A KR20200074034A KR102469725B1 KR 102469725 B1 KR102469725 B1 KR 102469725B1 KR 1020200074034 A KR1020200074034 A KR 1020200074034A KR 20200074034 A KR20200074034 A KR 20200074034A KR 102469725 B1 KR102469725 B1 KR 102469725B1
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- ultraviolet rays
- skin
- powder
- composition
- improving skin
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Abstract
본 발명은 들쭉나무 열매 분말을 유효성분으로 포함하는 피부노화 개선용 조성물에 관한 것으로, 보다 구체적으로 들쭉나무 열매 동결건조물 분말이 감소한 피부 장벽기능 및 피부 탄력을 증가시키고, 증가하는 염증을 감소시켜 피부노화를 개선시키며, 단쇄지방산을 증가시켜 피부노화를 개선할 수 있음을 확인하였으므로, 본 발명의 들쭉나무 열매 분말은 피부노화 개선용 조성물로 유용하게 사용될 수 있다. The present invention relates to a composition for improving skin aging comprising blueberry fruit powder as an active ingredient, and more specifically, blueberry fruit lyophilisate powder increases reduced skin barrier function and skin elasticity, and reduces increased inflammation, thereby reducing skin aging. Since it was confirmed that aging can be improved and skin aging can be improved by increasing short-chain fatty acids, the blueberry fruit powder of the present invention can be usefully used as a composition for improving skin aging.
Description
본 발명은 들쭉나무(Vaccinium uliginosum)를 이용하여 제조한 들쭉나무 열매 분말을 함유하는 피부노화 개선용 조성물에 관한 것으로, 보다 구체적으로 들쭉나무 열매 분말을 유효성분으로 함유하는 피부노화 개선용 조성물에 관한 것이다.The present invention relates to a composition for improving skin aging containing blueberry fruit powder prepared using Vaccinium uliginosum , and more particularly, to a composition for improving skin aging containing blueberry fruit powder as an active ingredient. will be.
최근에는 인공적인 약물과는 달리 비교적 부작용이 적은 천연물질에 대한 관심이 증가하고 있어 합성된 화장품보다 천연성분 화장품에 대한 선호도가 높아지고 있으며, 화장품 산업에 있어서 우수한 항산화 효능을 가지고 있는 천연물질을 사용한 노화방지, 자극완화, 주름개선, 미백 등의 연구가 활발하게 진행되고 있다. Recently, interest in natural substances with relatively few side effects, unlike artificial drugs, has increased, so preference for natural cosmetics over synthetic cosmetics is increasing, and aging using natural substances with excellent antioxidant efficacy in the cosmetics industry. Research on prevention, irritation relief, wrinkle improvement, whitening, etc. is being actively conducted.
신체를 보호하고 수분과 온도를 조절 및 보존하여 항상성을 유지하는 중요한 역할을 하는 피부의 노화과정은 면역기능 억제, 표피향상성 불균형, 호르몬 변화, 연령 증가, 스트레스 또는 개인의 유전적인 요인 등에 의한 내인성 노화(intrinsic aging)와 자외선이나 외부 물질의 자극 등에 의한 산화적 스트레스에 의한 외인성 노화(extrinsic aging)로 나눌 수 있다. 특히 외인성 노화는 주로 자외선에 의해 진행되므로 광노화(photo aging)라고도 불리며, 피부가 자외선에 노출되면 홍반, 부종, 화상반응, 색소침작, 거칠어짐, 탄력손실 및 주름과 같은 일변의 피부손상 혹은 노화과정이 촉진된다.The aging process of the skin, which plays an important role in maintaining homeostasis by protecting the body and regulating and preserving moisture and temperature, is caused by endogenous factors such as suppression of immune function, imbalance in epidermal enhancement, hormonal changes, age increase, stress, or individual genetic factors. It can be divided into intrinsic aging and extrinsic aging due to oxidative stress caused by ultraviolet rays or external substances. In particular, extrinsic aging is mainly caused by ultraviolet rays, so it is also called photo aging. When the skin is exposed to ultraviolet rays, skin damage or aging process such as erythema, edema, burn reaction, pigmentation, roughness, loss of elasticity, and wrinkles occur. this is promoted
내인성 노화는 세포수가 감소함에 따라 탄력이 감소되고, 수분 손실로 인해 각질층 구조가 변하는 미세한 주름, 피하지방층의 감소 등의 임상적인 특징을 가지지만 비교적으로 경미하다. 상기 외인성 노화는 자외선 자극으로 발생되는 활성 산소종(Reactive Oxygen Species, ROS)이 여러 전사인자를 활성화시켜 염증 유발과 관련된 사이토카인을 증가시키거나 피부의 장력과 강도, 탄력을 유지하며 피부보호 역할을 하는 진피 내 콜라겐, 엘라스틴과 같은 기질단백질을 감소시켜 굵고 깊은 주름이 발생하게 하고 피부가 건조해지고 탄력성이 감소하는 증상을 가져오게 한다. 외인성 노화의 80% 이상이 광노화에 의한 것으로 UVB(290~320nm)에 의한 것으로 염증성 피부질환, 광노화 및 암을 유발할 수 있는 가장 중요한 요소로 작용한다. UVB는 피부의 가장 바깥쪽인 표피층에 주로 작용하여 사이토카인(cytokine) 및 케모카인(chemokine)의 분비를 통해 염증반응을 일으키며, 종양괴사인자 알파(TNF-α), 인터류킨-6(interleukin-6, IL-6) 및 인터류킨-8(interleukin-8, IL-6)과 같은 전염증성 사이토카인을 유발하여 피부손상에 기여하는 것으로 확인되었다. 또한 UVB 노출에 의해 케라틴 세포에서 지속적으로 생성된 ROS는 효소, 비효소적인 방법에 의해 빠르게 제거되지만, 과생성된 ROS는 프리라티칼(free radical)을 생성하여 세포의 구조와 기능의 저하를 초래하고 세포내 비정상적인 유전자 발현의 결과를 가져온다. Endogenous aging has clinical features such as reduced elasticity as the number of cells decreases, fine wrinkles in which the structure of the stratum corneum changes due to water loss, and a decrease in the subcutaneous fat layer, but is relatively mild. In the extrinsic aging, reactive oxygen species (ROS) generated by UV stimulation activate several transcription factors to increase cytokines related to inflammation, maintain skin tension, strength, and elasticity, and play a role in skin protection. It reduces matrix proteins such as collagen and elastin in the dermis, which causes thick and deep wrinkles, and causes the skin to become dry and reduce elasticity. More than 80% of extrinsic aging is caused by photoaging, which is caused by UVB (290-320 nm), which acts as the most important factor that can cause inflammatory skin disease, photoaging, and cancer. UVB mainly acts on the outermost epidermal layer of the skin, causing an inflammatory response through the secretion of cytokines and chemokines, including tumor necrosis factor alpha (TNF-α), interleukin-6, It has been confirmed that it contributes to skin damage by inducing proinflammatory cytokines such as IL-6) and interleukin-8 (IL-6). In addition, ROS continuously generated in keratin cells by UVB exposure are quickly removed by enzymatic or non-enzymatic methods, but over-generated ROS generate free radicals, resulting in deterioration of cell structure and function. and result in abnormal gene expression in cells.
주름 발생 과정에 대한 명확한 이해는 아직 어려운 상황이지만, 진피의 콜라겐의 합성 저하 또는 분해 활성의 증가, 표피 기저막의 손상, 표피 대사 활성의 저하 등 주름 발생과 관련이 있는 다수의 결과들이 보고 되었고, 자외선으로 인해 유발되는 다양한 생화학적, 임상적 변화의 종합적인 영향에 의한 것으로 받아들여지고 있다. 피부 주름 문제를 해결하기 위해 콜라겐을 화장품으로 피부 표면에 도포하는 경우, 고분자인 콜라겐의 경피 흡수가 어려워 그 기능을 충분하게 기대할 수 없다는 문제가 있고, 진피에 직접 콜라겐을 주입하는 방법 역시 부작용에 의해 피부 주름을 개선하는 해결책이 되진 못하였다. Although it is still difficult to clearly understand the wrinkle formation process, a number of results related to wrinkle formation have been reported, such as decreased synthesis of collagen in the dermis or increased decomposition activity, damage to the epidermal basement membrane, and decreased epidermal metabolic activity. It is accepted that it is due to the comprehensive effect of various biochemical and clinical changes caused by In the case of applying collagen to the skin surface as a cosmetic to solve the problem of skin wrinkles, there is a problem that the percutaneous absorption of collagen, a polymer, is difficult to fully expect its function, and the method of directly injecting collagen into the dermis also has side effects due to side effects. It did not become a solution to improve skin wrinkles.
한편, 들쭉나무(Vaccinium uliginosum)는 진달래과 월귤나무속의 일종으로 낙엽활엽 소관목으로 높이 1m에 달하지만 한라산에서는 10 내지 15cm에 불과하며 가지는 갈색이고 어린가지에 잔털이 있거나 없다. 열매의 형태는 편구형, 원형, 서양배형 등 변이가 다양하다. 우리나라에서는 한라산과 설악산의 고지대에서만 드물게 자라고 있는 북방계 한대식물로 식물지리학적 주요성을 가지고 있다. 외국에서는 과실주, 주스, 파이 등에도 이용하고 있으나 원료공급이 부족한 실정으로 자원화 가치도 높은 편이다. 한방에서는 강정, 강장, 혈당저하, 모세혈관 강화, 야맹증 및 백내장 악화 방지, 괴혈병의 치료, 혈전용해제 등의 약용으로 다양하게 사용하였으며, 최근에 약리작용에 대한 연구도 활발하게 이루어져 항산화 및 항종양 활성, 기억력 증진 효과 등에 관한 연구가 보고되고 있다.On the other hand, blueberry tree ( Vaccinium uliginosum ) is a kind of azalea and bilberry, and it is a deciduous broad-leaved small shrub that reaches 1m in height, but it is only 10 to 15cm in Hallasan Mountain, and its branches are brown and have fine hairs on young branches. The shape of the fruit varies, such as oblate, round, and pear-shaped. In Korea, it is a northern boreal plant that rarely grows only in the highlands of Mt. Halla and Mt. Seorak, and has plant geographic importance. In foreign countries, it is also used for fruit wine, juice, and pies, but it is also highly valued as a resource due to the lack of raw material supply. In oriental medicine, it has been used in various ways for medicinal purposes such as gangjeong, tonic, lowering blood sugar, strengthening capillaries, preventing night blindness and cataract aggravation, treating scurvy, and thrombolytic agent. , studies on memory enhancement effects, etc. have been reported.
이에 본 발명자들은 피부노화 개선에 탁월한 물질을 개발하기 위해 연구해온 결과, 들쭉나무 열매 분말이 피부보호 및 주름개선 효과, 자외선으로 인해 감소되는 콜라겐, 엘라스틴 및 히알루론산의 함량 증가 효과 및 염증관련 인자 감소 효과가 우수함을 밝힘으로써 들쭉나무 열매 분말을 함유하는 피부노화 개선용 조성물을 발명하기에 이르렀다.Accordingly, the present inventors have studied to develop a substance excellent for improving skin aging, and as a result, blueberry fruit powder has skin protection and wrinkle improvement effects, an effect of increasing the content of collagen, elastin, and hyaluronic acid that is reduced due to ultraviolet rays, and reducing inflammation-related factors. By finding that the effect is excellent, a composition for improving skin aging containing blueberry fruit powder has been invented.
본 발명은 자외선으로 인한 피부노화를 개선하는 조성물을 제공하는 것이다. 또한, 본 발명의 조성물은 피부노화 개선용 화장료 조성물, 개선용 약제학적 조성물 및 건강식품으로 이용할 수 있다.The present invention provides a composition for improving skin aging caused by ultraviolet rays. In addition, the composition of the present invention can be used as a cosmetic composition for improving skin aging, a pharmaceutical composition for improving, and a health food.
본 발명은 들쭉나무 열매 분말이 외인성 노화의 주요 원인인 자외선에 의한 피부노화를 개선한다는 점을 확인하여, 들쭉나무 열매 분말을 포함하는 피부노화 개선용 조성물을 제공함으로써 상기 과제를 해결하였다.The present invention has confirmed that blueberry fruit powder improves skin aging caused by ultraviolet rays, which is a major cause of extrinsic aging, and has solved the above problems by providing a composition for improving skin aging containing blueberry fruit powder.
본 발명의 일 양태에서 들쭉나무 열매 분말은 들쭉나무 열매 동결건조물을 분쇄하여 제조할 수 있다.In one aspect of the present invention, blueberry fruit powder can be prepared by pulverizing blueberry fruit lyophilisate.
상기 들쭉나무 열매 분말은 피부노화 개선용 화장료 조성물, 약제학적 조성물 및 건강식품에 유효성분으로 함유될 수 있다.The blueberry fruit powder may be contained as an active ingredient in cosmetic compositions, pharmaceutical compositions, and health foods for improving skin aging.
본 발명은 외인성 노화의 주요 원인인 자외선으로 인해 감소하는 콜라겐 함량, 엘라스틴 함량, 히알루론산 함량을 증가시키고, 자외선으로 인해 증가하는 염증 관련 인자, 단백질 및 사이토카인을 감소시키며, 단쇄지방산을 증가시키는 피부노화 개선을 위한 들쭉나무 열매 분말을 제공할 수 있다.The present invention increases collagen content, elastin content, and hyaluronic acid content that decrease due to ultraviolet rays, which are the main causes of extrinsic aging, reduces inflammation-related factors, proteins, and cytokines that increase due to ultraviolet rays, and increases short-chain fatty acids. Blueberry fruit powder for aging improvement can be provided.
도 1은 들쭉나무 열매 분말 또는 추출물 분말의 자외선으로 인해 감소한 피부 내 수분 보유량의 증가 효과를 확인한 도이다.
(A) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 피부 내 수분보유량 변화 확인
(B) 자외선 조사 전과 후의 피부 내 수분보유량 변화 확인
도 2는 들쭉나무 열매 분말 또는 추출물 분말의 자외선으로 인해 증가한 경피수분손실량의 감소 효과를 확인한 도이다.
(A) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 경피수분손실량 변화 확인
(B) 자외선 조사 전과 후의 경피수분손실량 변화 확인
도 3은 들쭉나무 열매 분말 또는 추출물 분말의 자외선으로 인해 증가한 홍반수치의 감소 효과를 확인한 도이다.
(A) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 홍반수치 변화 확인
(B) 자외선 조사 전과 후의 홍반수치 변화 확인
도 4는 들쭉나무 열매 분말 또는 추출물 분말의 자외선으로 인해 증가한 피부 두께의 감소 효과를 확인한 도이다.
(A) 들쭉나무 열매 분말 또는 추출물 섭취 후 피부 두께 변화 확인
(B) 자외선 조사 전과 후의 피부 두께 변화 확인
도 5는 들쭉나무 열매 분말 또는 추출물 분말의 자외선으로 인해 증가한 주름의 개선 효과를 확인한 도이다.
(A) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 주름 개선 효과를 확인한 사진
(B) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 주름의 변화 확인
1) 총 주름 면적
2) 주름의 갯수
3) 주름의 평균 길이
4) 주름의 깊이
5) 주름의 평균 깊이
도 6은 들쭉나무 열매 분말 또는 추출물 분말의 자외선으로 인해 증가한 표피의 감소 효과를 확인한 도이다.
도 7은 들쭉나무 열매 분말 또는 추출물 분말의 자외선으로 인해 감소한 콜라겐의 증가 효과를 확인한 도이다.
(A) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 콜라겐 증가 효과를 확인한 사진
(B) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 콜라겐 변화 확인
도 8은 들쭉나무 열매 분말 또는 추출물 분말의 자외선으로 인해 감소한 엘라스틴의 증가 효과를 확인한 도이다.
도 9는 들쭉나무 열매 분말 또는 추출물 분말의 자외선으로 인해 증가한 콜라겐 분해효소(MMP)의 감소 효과를 확인한 도이다.
도 10은 들쭉나무 열매 분말 또는 추출물 분말의 자외선으로 인해 감소한 콜라겐 생성 효소(TIMP)의 증가 효과를 확인한 도이다.
도 11은 들쭉나무 열매 분말 또는 추출물 분말의 자외선으로 인해 감소한 1형 콜라겐(COL1a1)의 증가 효과를 확인한 도이다.
도 12는 들쭉나무 열매 분말 또는 추출물 분말의 자외선으로 인해 증가한 히알루론산 가수분해효소(HYAL)의 감소 효과를 확인한 도이다.
도 13은 들쭉나무 열매 분말 또는 추출물 분말의 자외선으로 인해 증가한 염증 관련 인자(NF-kB)의 감소 효과를 확인한 도이다.
도 14는 들쭉나무 열매 분말 또는 추출물 분말의 자외선으로 인해 증가한 AKT 및 mTOR의 감소효과를 확인한 도이다.
(A) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 AKT 1 발현량 변화 확인
(B) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 AKT 2 발현량 변화 확인
(C) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 mTOR 발현량 변화 확인
도 15는 들쭉나무 열매 분말 또는 추출물 분말의 자외선으로 인해 증가한 염증 관련 단백질의 감소 효과를 확인한 도이다.
(A) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 p-JNK 발현량 변화 확인
(B) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 p-ERK 발현량 변화 확인
(C) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 p-p38 발현량 변화 확인
도 16은 들쭉나무 열매 분말 또는 추출물 분말의 자외선으로 인해 증가한 염증 인자 사이토카인의 감소 효과를 확인한 도이다.
(A) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 IL-6 발현량 변화 확인
(B) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 IL-12 발현량 변화 확인
(C) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 TNF-α 발현량 변화 확인
도 17은 들쭉나무 열매 분말 또는 추출물 분말의 자외선으로 인해 감소한 단쇄지방산의 증가 효과를 확인한 도이다.
(A) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 아세트산 변화 확인
(B) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 프로피온산 변화 확인
(C) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 부티르산 변화 확인
(D) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 발레르산 변화 확인
(E) 들쭉나무 열매 분말 또는 추출물 분말 섭취 후 총 단쇄지방산 변화 확인1 is a diagram confirming the effect of increasing the amount of water retention in the skin reduced by ultraviolet rays of blueberry fruit powder or extract powder.
(A) Confirmation of changes in water retention in the skin after ingestion of blueberry fruit powder or extract powder
(B) Confirmation of changes in moisture content in the skin before and after UV irradiation
2 is a diagram confirming the effect of reducing the amount of transepidermal water loss increased by ultraviolet rays of blueberry fruit powder or extract powder.
(A) Confirmation of changes in transepidermal water loss after ingestion of blueberry fruit powder or extract powder
(B) Confirmation of changes in transepidermal water loss before and after UV irradiation
3 is a diagram confirming the effect of reducing erythema levels increased by ultraviolet rays of blueberry fruit powder or extract powder.
(A) Confirmation of change in erythema level after ingestion of blueberry fruit powder or extract powder
(B) Confirmation of changes in erythema levels before and after UV irradiation
4 is a diagram confirming the reduction effect of skin thickness increased by ultraviolet rays of blueberry fruit powder or extract powder.
(A) Confirmation of change in skin thickness after ingestion of blueberry fruit powder or extract
(B) Confirmation of skin thickness change before and after UV irradiation
5 is a diagram confirming the improvement effect of wrinkles increased by ultraviolet rays of blueberry fruit powder or extract powder.
(A) A photograph confirming the wrinkle improvement effect after ingesting blueberry fruit powder or extract powder
(B) Confirmation of changes in wrinkles after ingestion of blueberry fruit powder or extract powder
1) Total wrinkle area
2) Number of wrinkles
3) Average length of wrinkles
4) Depth of wrinkles
5) Average depth of wrinkles
6 is a diagram confirming the reduction effect of increased epidermis caused by ultraviolet rays of blueberry fruit powder or extract powder.
7 is a diagram confirming the effect of increasing collagen decreased by ultraviolet rays of blueberry fruit powder or extract powder.
(A) A photograph confirming the effect of increasing collagen after ingestion of blueberry fruit powder or extract powder
(B) Confirmation of collagen change after ingestion of blueberry fruit powder or extract powder
8 is a diagram confirming the effect of increasing elastin decreased by ultraviolet rays of blueberry fruit powder or extract powder.
9 is a diagram confirming the reduction effect of collagenase (MMP) increased by ultraviolet rays of blueberry fruit powder or extract powder.
10 is a diagram confirming the effect of increasing the collagen production enzyme (TIMP), which is decreased due to ultraviolet rays of blueberry fruit powder or extract powder.
11 is a diagram confirming the effect of increasing
12 is a diagram confirming the reduction effect of hyaluronic acid hydrolase (HYAL) increased by ultraviolet rays of blueberry fruit powder or extract powder.
13 is a diagram confirming the reduction effect of blueberry fruit powder or extract powder on inflammation-related factors (NF-kB) increased by ultraviolet light.
14 is a diagram confirming the reducing effect of blueberry fruit powder or extract powder on AKT and mTOR increased by ultraviolet light.
(A) Confirmation of change in
(B) Confirmation of change in
(C) Confirmation of change in mTOR expression level after ingestion of blueberry fruit powder or extract powder
15 is a diagram confirming the reduction effect of inflammation-related proteins increased by ultraviolet rays of blueberry fruit powder or extract powder.
(A) Confirmation of change in p-JNK expression level after ingestion of blueberry fruit powder or extract powder
(B) Confirmation of change in p-ERK expression level after ingestion of blueberry fruit powder or extract powder
(C) Confirmation of change in p-p38 expression level after ingestion of blueberry fruit powder or extract powder
16 is a diagram confirming the reduction effect of inflammatory factor cytokines increased by UV light of blueberry fruit powder or extract powder.
(A) Confirmation of change in IL-6 expression level after ingestion of blueberry fruit powder or extract powder
(B) Confirmation of change in IL-12 expression level after ingestion of blueberry fruit powder or extract powder
(C) Confirmation of change in TNF-α expression level after ingestion of blueberry fruit powder or extract powder
17 is a diagram confirming the effect of increasing short-chain fatty acids decreased by ultraviolet rays of blueberry fruit powder or extract powder.
(A) Confirmation of acetic acid change after ingestion of blueberry fruit powder or extract powder
(B) Confirmation of propionic acid change after ingestion of blueberry fruit powder or extract powder
(C) Verification of butyric acid change after ingestion of blueberry fruit powder or extract powder
(D) Confirmation of changes in valeric acid after ingestion of blueberry fruit powder or extract powder
(E) Confirmation of changes in total short-chain fatty acids after ingestion of blueberry fruit powder or extract powder
이하, 본원의 발명이 속하는 기술분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있도록 본 발명의 실시형태를 들어 상세히 설명한다. 본 발명의 실시형태는 당업계에서 평균적인 지식을 가진 자에게 본 발명을 더욱 완전하게 설명하기 위해서 제공되는 것이다. 따라서 본 발명의 실시형태는 여러 가지 다른 형태로 변형될 수 있으며, 본 발명의 범위가 이하 설명하는 실시형태로 한정되는 것은 아니다.Hereinafter, embodiments of the present invention will be described in detail so that those skilled in the art can easily practice the present invention. Embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art. Therefore, the embodiments of the present invention can be modified in many different forms, and the scope of the present invention is not limited to the embodiments described below.
본 발명은 들쭉나무(Vaccinium uliginosum) 열매 분말을 유효성분으로 함유하는 피부노화 개선용 조성물을 제공한다.The present invention provides a composition for improving skin aging containing Vaccinium uliginosum fruit powder as an active ingredient.
본 발명에 있어서 "개선"이란 조성물의 투여로 상기 질환의 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.In the present invention, "improvement" means any action that improves or beneficially changes the symptoms of the disease by administration of the composition.
본 발명에 있어서, "투여"는 임의의 적절한 방법으로 환자에게 소정의 물질을 제공하는 것을 의미하며, 본 발명의 조성물 투여 경로는 목적 조직에 도달할 수 있는 한 일반적인 모든 경로를 통하여 경구 또는 비경구 투여될 수 있다. 또한, 조성물은 임의의 장치에 의해 투여될 수 있다.In the present invention, "administration" means providing a predetermined substance to a patient by any suitable method, and the administration route of the composition of the present invention is oral or parenteral through all common routes as long as it can reach the target tissue. can be administered. In addition, the composition may be administered by any device.
상기 피부노화는 자외선이나 외부 물질의 자극 등에 의한 외인성 노화로, 염증 유발과 관련된 인자 증가, 콜라겐, 엘라스틴과 같은 기질단백질을 분해하는 효소 증가, 피부 건조, 탄력성 감소 및 기질단백질 감소로 인한 주름 발생 등의 임상적 특징일 수 있다.The skin aging is extrinsic aging caused by ultraviolet rays or external substances, such as increased inflammation-related factors, increased enzymes that decompose matrix proteins such as collagen and elastin, skin dryness, reduced elasticity, and reduced matrix proteins, resulting in wrinkles, etc. may be a clinical feature of
본 발명에 있어서, 들쭉나무 열매 분말은 들쭉나무 열매를 건조한 건조물을 분쇄하여 제조할 수 있다. 상기 건조물은 열매를 감압건조, 진공건조, 비등건조, 분무 건조 또는 동결건조하여 제조할 수 있다.In the present invention, blueberry fruit powder can be prepared by pulverizing dried blueberry fruit. The dried product may be prepared by drying the fruits under reduced pressure, vacuum drying, boiling drying, spray drying or freeze drying.
본 발명에 있어서 들쭉나무 열매 분말은 외인성 노화의 주요 원인인 자외선으로 인해 감소하는 피부 장벽 기능, 피부 탄력 및 증가하는 염증을 개선할 수 있다. In the present invention, blueberry fruit powder can improve skin barrier function, skin elasticity, and increased inflammation caused by ultraviolet rays, which are the main causes of extrinsic aging.
본 발명에 있어서 들쭉나무 열매 분말은 단쇄지방산을 증가시켜 피부노화를 개선할 수 있다. 상기 단쇄지방산은 장내 세균에 의해 생성되며 머리에 있는 지질막, 관절에 있는 지질막 및 피부에 있는 지질막에 공급되어 각 신체기관을 보호할 수 있다.In the present invention, blueberry fruit powder can improve skin aging by increasing short-chain fatty acids. The short-chain fatty acids are produced by intestinal bacteria and can be supplied to the lipid membrane in the head, the lipid membrane in the joints, and the lipid membrane in the skin to protect each body organ.
본 발명에 있어서 들쭉나무 열매 분말은 자외선으로 인해 발생할 수 있는 피부 장벽 손상을 방지할 수 있고, 피부 장벽 기능이 정상적으로 작용될 수 있도록 도움을 줄 수 있다. 상기 피부 장벽이 손상되어 발생하는 피부수분 감소, 경피수분 손실 및 홍반수치 증가를 개선시키고, 피부 장벽 손실로 인한 피부두께 증가 및 주름의 심화를 개선시킬 수 있다.In the present invention, blueberry fruit powder can prevent damage to the skin barrier that may occur due to ultraviolet rays, and can help the skin barrier function to function normally. It can improve skin moisture reduction, transepidermal water loss and increase in erythema level caused by damage to the skin barrier, and improve skin thickness and deepening of wrinkles due to skin barrier loss.
본 발명에 있어서 들쭉나무 열매 분말은 자외선으로 인해 발생할 수 있는 기질단백질 감소를 방지할 수 있다. 상기 기질단백질은 피부탄력에 도움이 되는 콜라겐(Collagen) 및 엘라스틴(Elastin)일 수 있다. 피부가 자외선에 노출되었을 때 감소하는 전체 콜라겐의 80~85%를 차지하는 1형 콜라겐(Collagen type I, COL1a1)의 유전자 발현량을 증가시키고, 광노화 되었을 때 함량 및 직경이 감소하는 엘라스틴의 함량을 증가시켜 피부노화를 개선시킬 수 있다. In the present invention, blueberry fruit powder can prevent matrix protein reduction that may occur due to ultraviolet rays. The matrix protein may be collagen and elastin, which are helpful for skin elasticity. Increases the gene expression of
또한, 피부가 자외선에 노출되었을 때 증가되는 활성산소에 의해 여러 전사인자가 활성화되고 그에 따라 발현되는 콜라겐 분해효소(Matrix metalloproteinase, MMP)인 MMP 2, MMP 3 및 MMP 9의 유전자 발현량을 감소시키고, MMP의 활성을 저해하는 콜라겐 생성 효소(Tissue inhibitor of metalloproteinases, TIMP)인 TIMP 1 및 TIMP 2의 유전자 발현량 및 콜라겐을 형성하는 프로콜라겐(Procollagen)의 발현량을 증가시켜 피부노화를 개선시킬 수 있다.In addition, when the skin is exposed to ultraviolet rays, various transcription factors are activated by the increased active oxygen, and the gene expression of
또한, 피부가 자외선에 노출되었을 때 신호전달을 거쳐 전사인자를 조절하여 콜라겐 엘라스틴과 같은 기질단백질이 분해하는 미토겐활성화단백질키나아제(mitogen-activated protein kinase, MAPK)의 발현량을 감소시켜 피부노화를 개선시킬 수 있다.In addition, when the skin is exposed to ultraviolet rays, it regulates transcription factors through signal transduction to reduce the expression level of mitogen-activated protein kinase (MAPK), which degrades matrix proteins such as collagen and elastin, thereby preventing skin aging. can be improved
본 발명에 있어서 들쭉나무 열매 분말은 자외선으로 인해 발생할 수 있는 피부보습인자 감소를 방지할 수 있다. 상기 피부보습인자는 히알루론산(Hyaluronan)일 수 있다. 피부가 자외선에 노출되었을 때 증가하는 히알루론산 가수분해 효소인 히알루로니다제(hyaluronidase, HYAL)의 발현량을 증가시켜 피부노화를 개선시킬 수 있다.In the present invention, blueberry fruit powder can prevent the decrease in skin moisturizing factor that may occur due to ultraviolet rays. The skin moisturizing factor may be hyaluronan. Skin aging can be improved by increasing the expression level of hyaluronidase (HYAL), a hyaluronic acid hydrolase that increases when the skin is exposed to ultraviolet rays.
본 발명에 있어서 들쭉나무 열매 분말은 자외선으로 인해 생성된 활성산소에 의해 활성이 증가할 수 있는 염증관련 인자, 단백질 및 사이토카인의 증가를 방지할 수 있다. 상기 염증관련 인자는 NF-kB 유전자일 수 있다. 상기 염증관련 단백질은 p-JNK, p-ERK 및 p-p38일 수 있다. 상기 염증관련 사이토카인은 IL-6(Interleukin-6), IL-12(Interleukin-12) 및 종양괴사인자 알파(Tumor necrosis factor-α)일 수 있다. 피부가 자외선에 노출되었을 때 증가하는 NF-kB 유전자, p-JNK, p-ERK, p-p38 단백질 및 IL-6, IL-12, TNF-α 사이토카인 발현량을 감소시켜 피부노화를 개선시킬 수 있다.In the present invention, blueberry fruit powder can prevent an increase in inflammation-related factors, proteins, and cytokines that can increase activity by active oxygen generated by ultraviolet rays. The inflammation-related factor may be the NF-kB gene. The inflammation-related proteins may be p-JNK, p-ERK, and p-p38. The inflammation-related cytokines may be IL-6 (Interleukin-6), IL-12 (Interleukin-12), and tumor necrosis factor-α (Tumor necrosis factor-α). It can improve skin aging by reducing the NF-kB gene, p-JNK, p-ERK, p-p38 protein, IL-6, IL-12, and TNF-α cytokine expression, which increase when the skin is exposed to UV rays. can
본 발명에 있어서 들쭉나무 열매 분말은 광노화에 영향을 주고 피부의 항상성 유지에 관여하는 신호 전달 경로인 AKT/mTOR 경로와 관련된 인자의 증가를 방지할 수 있다. 활성화된 AKT/mTOR 경로는 자가포식(Autophagy)을 억제할 수 있다. 자가포식은 정상적인 세포를 재생하여 세포 항상성을 유지하기 위해 죽은 세포의 구성성분을 자연적으로 분해하는 파괴 기재로, 피부 표피에서 환경스트레스에 대한 내성을 증가시키고 진피내의 콜라겐 및 엘라스틴과 같은 세포외 기질에 영향을 주며 피부의 항상성 유지에 관여하고 저해하는 역할을 한다. 상기 AKT/mTOR 경로와 관련된 인자는 AKT 1, AKT 2 및 포유류 라파마이신 표적(Mammalian target of rapamycin, mTOR) 유전자일 수 있다. 피부가 자외선에 노출되었을 때 증가하는 AKT 1, AKT 2 및 mTOR 유전자의 발현량을 감소시켜 피부노화를 개선시킬 수 있다.In the present invention, blueberry fruit powder can prevent an increase in factors related to the AKT/mTOR pathway, which is a signal transduction pathway that affects photoaging and is involved in maintaining skin homeostasis. Activated AKT/mTOR pathway can inhibit autophagy. Autophagy is a destructive mechanism that naturally decomposes components of dead cells to regenerate normal cells and maintain cell homeostasis. It affects and plays a role in maintaining homeostasis of the skin and inhibiting it. Factors related to the AKT/mTOR pathway may be
본 발명에 있어서 들쭉나무 열매 분말은 자외선으로 인해 발생할 수 있는 단쇄지방산 감소를 방지하여 피부노화를 개선할 수 있도록 도움을 줄 수 있다.In the present invention, blueberry fruit powder can help improve skin aging by preventing the reduction of short-chain fatty acids that may occur due to ultraviolet rays.
상기 단쇄지방산은 이중결합이 하나 있는, 탄소수 6 이하의 지방산으로, 포름산(Formic acid), 아세트산(Acetic acid), 프로피온산(Propionic acid), 부티르산(Butyric acid), 아이소부티르산(Isobutyric acid), 발레르산(Valeric acid) 및 아이소발레르산(Isovaleric acid)으로 구성된 군에서 선택되는 하나 이상일 수 있다.The short-chain fatty acids are fatty acids having one double bond and having 6 or less carbon atoms, such as formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, and valeric acid. (Valeric acid) and isovaleric acid (Isovaleric acid) may be at least one selected from the group consisting of.
본 발명의 들쭉나무 열매 분말을 함유하는 조성물은 상기 성분에 추가로 동일 또는 유사한 기능을 나타내는 유효성분을 1종 이상 함유할 수 있다.The composition containing blueberry fruit powder of the present invention may contain one or more active ingredients exhibiting the same or similar functions in addition to the above ingredients.
본 발명은 들쭉나무 열매 분말을 유효성분으로 함유하는 피부노화 개선용 화장료 조성물을 제공할 수 있다. The present invention can provide a cosmetic composition for improving skin aging containing blueberry fruit powder as an active ingredient.
상기 화장료 조성물은 본 발명의 들쭉나무 열매 분말에 피부학적으로 허용가능한 담체를 혼합하여 사용될 수 있으며, 이때 피부학적으로 허용되는 담체는 정제수, 오일, 왁스, 지방산, 지방산 알코올, 지방산 에스테르, 계면활성제, 흡습제(humectant), 증점제(thickening agent), 항산화제, 점도 안정화제(viscosity stabilizer), 킬레이팅제, 완충제, 방부제, 저급 알코올 등이 포함될 수 있지만 이에 한정되는 것은 아니고 그 종류와 농도가 다양하고 당업자가 본 발명의 사상 및 영역으로부터 벗어나지 않는 범위 내에서 수정 및 변경할 수 있는 부분을 포함할 수 있다. 필요에 따라 미백제, 보습제, 항염증제, 항박테리아제, 항진균제, 비타민, 자외선 차단제, 항생제, 여드름 방지제, 향수, 염료가 포함될 수 있으며, 이들은 화장품 분야에서 통상적으로 사용되는 양으로 본 발명에 따른 피부노화 개선용 화장료 조성물에 포함될 수 있다. The cosmetic composition may be used by mixing the blueberry fruit powder of the present invention with a dermatologically acceptable carrier, wherein the dermatologically acceptable carrier is purified water, oil, wax, fatty acid, fatty acid alcohol, fatty acid ester, surfactant, It may include, but is not limited to, a humectant, a thickening agent, an antioxidant, a viscosity stabilizer, a chelating agent, a buffer, a preservative, a lower alcohol, etc. may include parts that can be modified and changed within the scope not departing from the spirit and scope of the present invention. If necessary, a whitening agent, a moisturizing agent, an anti-inflammatory agent, an antibacterial agent, an antifungal agent, a vitamin, a sunscreen agent, an antibiotic, an anti-acne agent, a perfume, and a dye may be included. It may be included in the cosmetic composition for use.
또한, 본 발명의 들쭉나무 열매 분말을 포함하는 화장료 조성물로부터 제조되는 화장품은 일반적인 유화 제형 및 가용화 제형의 형태로 제조할 수 있으며, 상기 유화 제형의 화장품으로는 영양화장수, 크림, 에센스 등 일 수 있고, 상기 가용화 제형의 화장품으로는 유연화장수 일 수 있다. 또한 적합한 화장품의 제형으로는 용액, 겔, 고체 또는 반죽 무수 생성물, 수상에 유상을 분산시켜 얻은 에멀젼, 현탁액, 마이크로에멀젼, 마이크로캡슐, 미세과립구 또는 이온형(리포좀), 비이온형의 소낭 분산제의 형태, 크림, 스킨, 로션, 파우더, 연고, 스프레이 또는 콘실 스틱(conceal stick)의 형태로 제공될 수 있고, 포말(foam)의 형태 또는 압축된 추진제를 더 함유한 에어로졸 조성물의 형태로도 제조될 수 있다. In addition, cosmetics prepared from the cosmetic composition containing the blueberry fruit powder of the present invention can be prepared in the form of a general emulsion formulation and a solubilized formulation, and the cosmetic of the emulsion formulation may be a nutritional lotion, cream, essence, etc. , Cosmetics of the solubilization formulation may be softening lotion. In addition, suitable cosmetic formulations include solutions, gels, solid or kneaded anhydrous products, emulsions obtained by dispersing an oil phase in an aqueous phase, suspensions, microemulsions, microcapsules, microgranules or ionic (liposomes), and nonionic vesicle dispersants. It may be provided in the form of a cream, toner, lotion, powder, ointment, spray or conceal stick, and may also be prepared in the form of a foam or an aerosol composition further containing a compressed propellant. can
또한, 본 발명의 들쭉나무 열매 분말은 수렴화장수, 유연화장수, 영양화장수, 각종 크림, 에센스, 팩, 파운데이션 등과 같은 화장품류와 클렌징, 세안제, 비누, 트리트먼트 또는 미용액에 첨가하여 제품을 제조할 수 있고, 상기 제품의 구체적인 제형은 스킨로션, 스킨 소프너, 스킨토너, 아스트린젠트, 로션, 밀크로션, 모이스처 로션, 영양로션, 마사지크림, 영양크림, 모이스처 크림, 핸드크림, 에센스, 영양 에센스, 팩, 비누, 샴푸, 클렌징폼, 클렌징로션, 클렌징크림, 바디로션, 바디클렌저, 유액, 프레스파우더, 루스파우더 또는 아이섀도 등의 제형일 수 있다. In addition, the blueberry fruit powder of the present invention can be added to cosmetic products such as astringent lotion, softening lotion, nutrient lotion, various creams, essences, packs, foundations, etc. And, the specific formulation of the product is skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrient lotion, massage cream, nutrient cream, moisture cream, hand cream, essence, nutrient essence, pack, soap , Shampoo, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, emulsion, press powder, loose powder, or may be a formulation such as eye shadow.
또한, 본 발명은 들쭉나무 열매 분말을 유효성분으로 함유하는 피부노화 개선용 약제학적 조성물을 제공할 수 있다.In addition, the present invention contains blueberry fruit powder as an active ingredient A pharmaceutical composition for improving skin aging can be provided.
상기 약제학적 조성물은 본 발명의 들쭉나무 열매 분말에 약제학적으로 허용 가능한 첨가제를 더 포함할 수 있으며, 이때 약제학적으로 허용 가능한 첨가제로는 전분, 젤라틴화 전분, 미결정셀룰로오스, 유당, 포비돈, 콜로이달실리콘디옥사이드, 미결정셀룰로오스, 유당, 포비돈, 콜로이달실리콘디옥사이드, 인산수소칼슘, 락토스, 만니톨, 엿, 아라비아고무, 전호화전분, 옥수수전분, 분말셀룰로오스, 히드록시프로필셀룰로오스, 오파드라이, 전분글리콜산나트륨, 카르나우바 납, 합성규산알루미늄, 스테아린산, 스테아린산마그네슘, 스테아린산알루미늄, 스테아린산칼슘, 백당, 덱스트로스, 소르비톨 및 탈크 등이 사용될 수 있다. 본 발명에 따른 약제학적으로 허용 가능한 첨가제는 상기 조성물에 대해 0.1 ~ 90 중량부 포함될 수 있다.The pharmaceutical composition may further contain pharmaceutically acceptable additives to the blueberry fruit powder of the present invention, wherein the pharmaceutically acceptable additives include starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, and colloidal. Silicon Dioxide, Microcrystalline Cellulose, Lactose, Povidone, Colloidal Silicon Dioxide, Calcium Hydrogen Phosphate, Lactose, Mannitol, Taffy, Gum Arabic, Pregelatinized Starch, Corn Starch, Powdered Cellulose, Hydroxypropyl Cellulose, Opadry, Sodium Starch Glycolate , carnauba lead, synthetic aluminum silicate, stearic acid, magnesium stearate, aluminum stearate, calcium stearate, white sugar, dextrose, sorbitol and talc, and the like can be used. Pharmaceutically acceptable additives according to the present invention may be included in an amount of 0.1 to 90 parts by weight based on the composition.
또한, 본 발명의 들쭉나무 열매 분말은 실제 임상 투여 시에 경구 및 비경구의 여러 가지 제형으로 투여될 수 있는데, 제제화 할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형 제제는 들쭉나무 열매 분말에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(Calcium carbonate), 수크로스(Sucrose), 락토오스(Lactose) 또는 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용될 수 있다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제 및 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 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 포함될 수 있다. 비수성용제, 현탁용제로는 프로필렌글리콜(Propylene glycol), 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, 글리세로제라틴 등이 사용될 수 있다. 또한 본 발명의 들쭉나무 열매 분말은 목적하는 방법에 따라 경구 투여하거나 비경구 투여할 수 있으며, 비경구 투여시 피부 외용 또는 복강내주사, 직장내주사, 피하주사, 정맥주사, 근육내 주사 또는 흉부내 주사 주입방식을 선택할 수 있다. 투여량은 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설률 및 질환의 중증도 등에 따라 그 범위가 다양하다.In addition, the blueberry fruit powder of the present invention can be administered in various oral and parenteral formulations during actual clinical administration. When formulated, commonly used fillers, extenders, binders, wetting agents, disintegrants, surfactants It may be formulated using diluents or excipients. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations contain at least one excipient such as starch, calcium carbonate, sucrose in blueberry fruit powder. It may be prepared by mixing sucrose, lactose, or gelatin. In addition to simple excipients, lubricants such as magnesium styrate and talc may also be used. Liquid formulations for oral use include suspensions, solutions for oral use, emulsions, and syrups. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. . Preparations for parenteral administration may include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, witepsol, macrogol, tween 61, cacao butter, laurin fat, glycerogeratin and the like may be used. In addition, the blueberry fruit powder of the present invention can be administered orally or parenterally depending on the desired method, and in the case of parenteral administration, external skin or intraperitoneal injection, intrarectal injection, subcutaneous injection, intravenous injection, intramuscular injection or chest injection I can choose my injection method. The dosage varies depending on the patient's weight, age, sex, health condition, diet, administration time, administration method, excretion rate, and severity of the disease.
또한, 본 발명에 따른 들쭉나무 열매 분말은 약제학적으로 유효한 양으로 투여한다. 본 발명에 있어서 "약제학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효용량 수준은 환자 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 들쭉나무 열매 분말은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있으며, 단일 또는 다중 투여될 수 있다. 상기한 요소들을 모두 고려하여 부작용없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다. 구체적으로 본 발명에 따른 들쭉나무 열매 분말의 유효량은 환자의 나이, 성별, 체중에 따라 달라질 수 있으며, 일반적으로는 체중 1 kg 당 0.1 mg 내지 1000 mg, 바람직하게는 10 mg 내지 500 mg을 매일 또는 격일 투여하거나 1일 1 내지 3회로 나누어 투여할 수 있다. 그러나 투여 경로, 비만의 중증도, 성별, 체중, 연령 등에 따라서 증감될 수 있으므로 상기 투여량이 어떠한 방법으로도 본 발명의 범위를 한정하는 것은 아니다.In addition, blueberry fruit powder according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level is the type of patient's disease, severity, activity of the drug, drug It may be determined according to factors including sensitivity to , time of administration, route of administration and excretion rate, duration of treatment, drugs used concurrently, and other factors well known in the medical field. The blueberry fruit powder of the present invention can be administered as an individual therapeutic agent or in combination with other therapeutic agents, sequentially or simultaneously with conventional therapeutic agents, and can be administered single or multiple times. Considering all of the above factors, it is important to administer an amount that can obtain the maximum effect with the minimum amount without side effects, which can be easily determined by those skilled in the art. Specifically, the effective amount of blueberry fruit powder according to the present invention may vary depending on the patient's age, sex, and weight, and is generally 0.1 mg to 1000 mg, preferably 10 mg to 500 mg per 1 kg of body weight per day or It can be administered every other day or divided into 1 to 3 times a day. However, since it may increase or decrease depending on the route of administration, severity of obesity, gender, weight, age, etc., the dosage is not limited to the scope of the present invention in any way.
또한, 본 발명은 들쭉나무 열매 분말을 유효성분으로 함유하는 피부노화 개선용 건강식품을 제공할 수 있다.In addition, the present invention can provide a health food for improving skin aging containing blueberry fruit powder as an active ingredient.
상기 건강식품은 본 발명의 들쭉나무 열매 분말을 식품에 그대로 첨가하거나 다른 식품 또는 식품성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효성분의 혼합량은 그의 사용 목적(예방 또는 개선용)에 따라 적합하게 결정될 수 있다. 일반적으로, 건강식품 중의 상기 들쭉나무 열매 분말의 양은 전체 식품 중량의 0.01 내지 15 중량%, 바람직하게는 0.1 내지 5 중량%로 가할 수 있으며 건강음료 조성물에는 100을 기준으로 0.01 내지 5.0 g, 바람직하게는 0.01 내지 1.0 g의 비율로 첨가할 수 있다. 그러나 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다. 본 발명의 건강 기능성 음료 조성물은 지시된 비율로 필수 성분으로서 상기 화합물을 함유하는 외에는 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상기 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어, 말토스, 수크로즈 등 및 폴리사카라이드, 예를 들어, 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리스리톨 등의 당알코올이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마킨, 스테비아 추출물 등), 및 합성 향미제(사카린, 아스파르탄 등)를 유리하게 사용할 수 있다. 또한, 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 당 일반적으로 약 0.1 내지 2.0 g, 바람직하게는 약 0.1 내지 1.0 g이다.As the health food, the blueberry fruit powder of the present invention may be added to food as it is or used together with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined depending on the purpose of use (for prevention or improvement). In general, the amount of the blueberry fruit powder in the health food may be added at 0.01 to 15% by weight, preferably 0.1 to 5% by weight, based on the weight of the total food, and in the health drink composition, 0.01 to 5.0 g based on 100, preferably may be added at a rate of 0.01 to 1.0 g. However, in the case of long-term intake for the purpose of health control, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range. The health functional beverage composition of the present invention is not particularly limited in other components except for containing the compound as an essential component in the indicated ratio, and may contain various flavoring agents or natural carbohydrates as additional components like conventional beverages. Examples of the natural carbohydrates include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (such as taumachin and stevia extract) and synthetic flavoring agents (such as saccharin and aspartan) can be advantageously used. In addition, the proportion of the natural carbohydrate is generally about 0.1 to 2.0 g, preferably about 0.1 to 1.0 g per 100 of the composition of the present invention.
또한, 본 발명의 건강기능식품은 식품의 제조공정 중에 상술한 본 발명의 들쭉나무 열매 분말을 첨가하는 공정을 가함으로써 또는 식품의 제조 후에 상술한 본 발명의 추출물을 첨가하는 공정을 가함으로써 용이하게 얻을 수 있다. 이때 필요에 따라 맛과 냄새 교정제를 첨가하여도 좋다. 상기 외에 본 발명의 들쭉나무 열매 분말은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 중점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 들쭉나무 열매는 천연 과일 주스 및 과일 주스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 들쭉나무 열매 분말 100 중량부 당 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition, the health functional food of the present invention can be easily obtained by adding the above-described blueberry fruit powder of the present invention during the food manufacturing process or by adding the above-described extract of the present invention after food preparation. You can get it. At this time, a taste and odor corrector may be added if necessary. In addition to the above, the blueberry fruit powder of the present invention contains various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectic acid and its salts, Alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like may be contained. In addition, the fruit of the blueberry tree of the present invention may contain fruit flesh for the production of natural fruit juice, fruit juice beverage, and vegetable beverage. These components may be used independently or in combination. The proportion of these additives is not critical, but is generally selected in the range of about 20 parts by weight per 100 parts by weight of blueberry fruit powder of the present invention.
본 발명의 구체적인 실시예에서, 본 발명자들은 들쭉나무 열매 분말을 제조하고 상기 들쭉나무 열매 분말의 피부노화 개선 효과를 확인하였다. 등 피부에 자외선을 쬐어 광노화가 유발된 마우스를 이용하여 동물실험을 수행한 결과, 수분보유량 증가, 경피수분손실량 감소, 피부 두께 감소, 홍반수치 감소, 피부 두께 및 주름 감소, 표피 두께 감소, 콜라겐 비율 및 엘라스틴 양 증가 효과를 확인하여 자외선으로 인해 저하된 피부보호 및 피부노화 개선 효과를 확인하였다. In a specific embodiment of the present invention, the present inventors prepared blueberry fruit powder and confirmed the skin aging improvement effect of the blueberry fruit powder. As a result of animal experiments using mice in which photoaging was induced by exposure to ultraviolet rays on the back skin, water retention increased, transepidermal water loss decreased, skin thickness decreased, erythema level decreased, skin thickness and wrinkles decreased, epidermal thickness decreased, and collagen ratio And by confirming the effect of increasing the amount of elastin, the skin protection and skin aging improvement effect reduced by ultraviolet rays were confirmed.
또한 본 발명의 구체적인 실험예에서, 피부 관련 유전자인 콜라겐 분해효소의 발현량 감소, 콜라겐 분해효소 활성 저해 유전자의 발현량 증가, 콜라겐 생합성 유전자의 발현량 증가 및 피부 보습인자 히알루론산의 분해효소의 발현량 감소 효과를 확인하여 피부노화 개선 효과를 확인하였다.In addition, in a specific experimental example of the present invention, the expression of collagen degrading enzyme, which is a skin-related gene, decreased, increased expression of collagen degrading enzyme activity inhibitory gene, increased expression of collagen biosynthesis gene, and expression of skin moisturizing factor hyaluronic acid degrading enzyme The effect of reducing the amount was confirmed to confirm the effect of improving skin aging.
또한 본 발명의 구체적인 실험예에서, 염증 유발 관련 인자, 단백질 및 사이토카인의 발현량 감소, 광노화에 영향을 주는 AKT/mTOR 경로 관련 인자 발현량 감소 효과를 확인하여 피부노화 개선 효과를 확인하였다.In addition, in a specific experimental example of the present invention, the effect of reducing the expression level of factors related to inflammation, proteins and cytokines, and the expression level of factors related to the AKT/mTOR pathway affecting photoaging was confirmed, thereby confirming the effect of improving skin aging.
또한, 본 발명의 구체적인 실험예에서, 단쇄지방산 증가 효과를 확인하여 피부노화 개선 효과를 확인하였다.In addition, in a specific experimental example of the present invention, the effect of improving skin aging was confirmed by confirming the effect of increasing short-chain fatty acids.
또한, 본 발명의 구체적인 실험예에서 통상 원물(분말)이 추출물에 비해 효과가 좋지 않은 않지만, 들쭉나무 열매의 경우 분말이 추출물보다 낮은 농도에서 더 우수한 효과를 나타냄을 확인하였다.In addition, in a specific experimental example of the present invention, it was confirmed that the raw material (powder) usually has a lower effect than the extract, but in the case of blueberry fruit, the powder shows a better effect than the extract at a lower concentration.
이하, 본 발명을 실시예 및 실험예를 통해 보다 상세히 설명한다. 다만 하기 실시예 및 실험예는 본 발명의 이해를 돕기 위한 것이지 본 발명의 권리범위를 이로 한정하는 것을 의도하지 않는다.Hereinafter, the present invention will be described in more detail through Examples and Experimental Examples. However, the following examples and experimental examples are intended to aid understanding of the present invention and are not intended to limit the scope of the present invention thereto.
<실시예 1> 들쭉나무 열매 분말의 제조<Example 1> Preparation of blueberry fruit powder
동결건조된 북한산 들쭉나무의 열매 270 g을 분쇄한 후, 말토덱스트린 27 g및 이산화규소 3 g을 혼합하여 들쭉 열매 분말을 제조하였다.After pulverizing 270 g of freeze-dried blueberry fruit from North Korea, blueberry fruit powder was prepared by mixing 27 g of maltodextrin and 3 g of silicon dioxide.
<비교예 1> 들쭉나무 열매 추출물 분말의 제조<Comparative Example 1> Preparation of blueberry fruit extract powder
동결건조된 들쭉나무 열매 300 g을 50%의 주정 3 L와 함께 50℃의 항온수조에서 4시간 온탕하여 들쭉나무 열매 추출물을 얻는 과정을 2번 반복한 후, 상기 들쭉나무 열매 추출물을 No. 3 여과지(Whatman International Limited, Kent England)로 여과하여 불순물이 제거된 추출물을 얻었다. 상기 추출물을 회전농축기를 이용하여 50℃에서 감압하여 농축시킨 후 고형분을 측정하고, 측정된 고형분의 50%에 해당하는 말토텍스트린을 첨가 후 동결건조하여 들쭉나무 열매 추출 분말을 제조하였다.300 g of freeze-dried blueberry fruit was warmed with 3 L of 50% alcohol in a constant temperature water bath at 50° C. for 4 hours to obtain a blueberry fruit extract twice. 3 filter paper (Whatman International Limited, Kent England) to obtain an extract from which impurities were removed. After concentrating the extract under reduced pressure at 50° C. using a rotary evaporator, the solid content was measured, and maltodextrin corresponding to 50% of the measured solid content was added and lyophilized to prepare blueberry fruit extract powder.
<실험예 1> 자외선에 의한 피부노화 개선 효과 확인<Experimental Example 1> Confirmation of skin aging improvement effect by ultraviolet rays
자외선에 의한 피부의 노화 현상을 확인하기 위해 동물실험을 수행하였고, 고려대학교 동물실험윤리위원회 승인을 받은 후(IACUC 승인번호: KUIACUC-2019-0062) ‘실험동물 관리 및 이용에 관한 지침(Guide for the Care and Use of Laboratory Animals, NRC)'에 맞추어 관리하며 실시하였다. 실험동물은 SKH-1 무모쥐(Hariless mice, 25~27 g, 5주령) 수컷을 오리엔탈바이오에서 구매하여 전용 사육 케이지에서 케이지 당 3마리씩 사육하였고, 동물 사육실 환경 온도는 21±1℃, 상대습도는 50~55%, 명암은 12시간 주기, 음수와 사료는 자유급식으로 실시하였다.Animal experiments were conducted to confirm the aging of the skin caused by UV rays, and after obtaining approval from the Animal Experimentation Ethics Committee of Korea University (IACUC approval number: KUIACUC-2019-0062), the 'Guide for the Care and Use of Laboratory Animals' was published. The Care and Use of Laboratory Animals (NRC)'. As experimental animals, male SKH-1 Hariless mice (25-27 g, 5 weeks old) were purchased from Oriental Bio and raised 3 per cage in a dedicated breeding cage. was 50-55%, light and dark were given a 12-hour cycle, and drinking water and feed were provided with free feeding.
실험군은 총 6군(군당 6마리)으로 정상대조군(normal, not UVB-induced), 음성대조군(control, UVB-irradiate), 들쭉나무 열매 건조물 저농도 처리군(UL, low dose of V. uliginosum, 50 mg/kg) 및 고농도 처리군(UH, high dose of V. uliginosum, 100 mg/kg), 들쭉나무 열매 추출물 저농도 처리군(EL, low dose of extract, 100 mg/kg) 및 중간농도 처리군(EM, middle dose of extract, 200 mg/kg)으로 분류하였고, 일주일 동안의 적응기가 지난 후 정상대조군(NOR)을 제외한 6군에 8주간 주 3회 UVB-자외선램프(T-8M; Vilber Lourmat, France)가 부착된 자외선 조사기(BLX-254; Vilber Lourmat, France)를 이용하여 등 피부에 자외선을 쬐어 광노화를 유발하였다. 자외선 조사량은 UV Light meter(UV-340; Lutron, Taiwan)로 자외선 조사기 내부의 조사량을 측정하여 조정한 뒤 하기 표 1과 같이 UVB 조사량을 조절하였다.The experimental groups consisted of a total of 6 groups (6 animals per group): a normal control group (normal, not UVB-induced), a negative control group (control, UVB-irradiate), and a low dose of dried blueberry fruit treatment group (UL, low dose of V. uliginosum, 50 mg/kg) and high dose treatment group (UH, high dose of V. uliginosum, 100 mg/kg), blueberry fruit extract low concentration treatment group (EL, low dose of extract, 100 mg/kg) and medium concentration treatment group ( EM, middle dose of extract, 200 mg/kg), and after a week-long adaptation period, 6 groups except for the normal control group (NOR) were treated with a UVB-ultraviolet lamp (T-8M; Vilber Lourmat, France) was applied to the back skin using a UV irradiator (BLX-254; Vilber Lourmat, France) to induce photoaging. The UV irradiation amount was adjusted by measuring the irradiation amount inside the UV irradiator with a UV Light meter (UV-340; Lutron, Taiwan), and then the UVB irradiation amount was adjusted as shown in Table 1 below.
1 MED = 75 mJ/cm2 1 MED = 75 mJ/cm 2
자외선 조사 시작일로부터 8주간 정상대조군(NOR)과 음성대조군(CON)은 음용수만 경구투여하였고, 시료 처리군은 체중 측정 후 상기 <실시예 1>의 들쭉나무 열매 분말 또는 <비교예 1>의 들쭉나무 열매 추출물 분말을 농도에 맞추어 증류수에 녹인 시료를 음용수와 혼합하여 경구투여하였다.For 8 weeks from the start of UV irradiation, only drinking water was orally administered to the normal control group (NOR) and the negative control group (CON), and the sample treatment group measured the weight, and then the blueberry fruit powder of <Example 1> or the blueberry fruit of <Comparative Example 1> Samples of tree fruit extract powder dissolved in distilled water according to the concentration were mixed with drinking water and administered orally.
자외선 조사 시작 전 모든 그룹에서 피부측정이 진행되었고, 자외선에 의한 피부 광노화 현상을 확인하기 위해 NOR과 CON 사이의 피부 측정 결과에서 유의적인 차이가 나타나는 것을 확인하고자 자외선 조사 4주 이후부터 일주일 간격으로 피부측정을 진행하였다. 실험 결과로 마지막을 피부를 측정한 결과값과 마지막으로 측정한 결과값 및 자외선 조사 전 초기 피부를 측정한 결과값의 변화량을 확인하였다.Skin measurement was conducted in all groups before the start of UV irradiation, and to confirm that there was a significant difference in the skin measurement results between NOR and CON to confirm the skin photoaging phenomenon caused by UV rays, skin measurements were taken at intervals of one week from 4 weeks after UV irradiation. measurement was carried out. As a result of the experiment, the amount of change between the final skin measurement result, the last measurement result, and the initial skin measurement result before UV irradiation was confirmed.
<1-1> 비침습적(Non-invasive) 측정방법을 이용한 피부 상태 평가<1-1> Skin condition evaluation using non-invasive measurement method
자외선을 조사한 쥐의 등 쪽 피부를 비침습적 측정방법인 Multi Probe Adapter® MPA 6(Courage und Khazaka, Germany)를 이용하여 피부손상 정도를 확인할 수 있는 수분보유량, 경피수분손실량(Transepidermal Water Loss, TEWL) 및 홍반 수치를 확인하였다. 피부 두께는 digital micrometer(Model 293; Mitutoyo, Japan)로 측정하였다.Water retention and Transepidermal Water Loss (TEWL) that can check the degree of skin damage using Multi Probe Adapter® MPA 6 (Courage und Khazaka, Germany), a non-invasive measurement method for the back skin of rats irradiated with ultraviolet rays and erythema levels were confirmed. Skin thickness was measured with a digital micrometer (Model 293; Mitutoyo, Japan).
<1-1-1> 수분보유량의 변화량 확인<1-1-1> Check the amount of change in water retention
수분보유량을 확인한 결과, 전체 시료 투여군에서 CON 대비 증가하는 효과를 확인하였고, 시료 투여군 중 UL군에서 유의적으로 증가함을 확인하였다(도 1 (A)).As a result of checking the water retention, it was confirmed that the effect of increasing compared to CON was confirmed in the entire sample administration group, and it was confirmed that it increased significantly in the UL group among the sample administration groups (Fig. 1 (A)).
또한, 자외선 조사 전과 후의 변화량을 확인한 결과, 전체 시료 투여군에서 CON 대비 감소량이 적음을 확인하였고, 시료 투여군 중 UL군에서 감소량이 가장 적음을 확인하였다(도 1 (B)).In addition, as a result of confirming the amount of change before and after UV irradiation, it was confirmed that the amount of decrease compared to CON was small in the entire sample administration group, and the decrease was the smallest in the UL group among the sample administration groups (FIG. 1 (B)).
<1-1-2> 경피수분손실량의 변화량 확인<1-1-2> Confirmation of change in transepidermal water loss
경피수분손실량을 확인한 결과, 전체 시료 투여군에서 CON 대비 감소하는 효과를 확인하였고, 시료 투여군 중 UL 및 UH 군에서 유의적으로 감소함을 확인하였다(도 2 (A)).As a result of confirming the transepidermal water loss, it was confirmed that the effect of decreasing compared to CON was confirmed in the entire sample administration group, and it was confirmed that it was significantly reduced in the UL and UH groups among the sample administration groups (Fig. 2 (A)).
또한, 자외선 조사 전과 후의 변화량을 확인한 결과, 전체 시료 투여군에서 CON 대비 감소량이 적음을 확인하였고, 시료 투여군 중 UL 및 UH 군에서 유의적으로 감소량이 적음을 확인하였다(도 2 (B)).In addition, as a result of confirming the amount of change before and after UV irradiation, it was confirmed that the amount of decrease compared to CON was small in the entire sample administration group, and it was confirmed that the amount of decrease was significantly less in the UL and UH groups among the sample administration groups (Fig. 2 (B)).
<1-1-3> 홍반수치 변화량 확인<1-1-3> Check the amount of change in erythema level
홍반수치를 확인한 결과, 전체 시료 투여군에서 CON 대비 감소하는 효과를 확인하였고, 시료 투여군 중 UH 및 EM 군에서 유의적으로 감소함을 확인하였다(도 3 (A)).As a result of confirming the erythema level, it was confirmed that the effect of decreasing compared to CON was confirmed in the entire sample administration group, and it was confirmed that it was significantly reduced in the UH and EM groups among the sample administration groups (FIG. 3 (A)).
또한, 자외선 조사 전과 후의 변화량을 확인한 결과, UH 및 EM 군에서 감소함을 확인하였다(도 3 (B)).In addition, as a result of confirming the amount of change before and after UV irradiation, it was confirmed that it decreased in the UH and EM groups (FIG. 3 (B)).
<1-1-4> 피부 두께 변화량 확인<1-1-4> Check skin thickness change
피부 두께를 확인한 결과, 전체 시료 투여군에서 CON 대비 감소하는 효과를 확인하였다(도 4 (A)).As a result of confirming the skin thickness, the effect of decreasing compared to CON was confirmed in the entire sample administration group (FIG. 4 (A)).
또한, 자외선 조사 전과 후의 변화량을 확인한 결과, 전체 시료 투여군에서 CON 대비 감소함을 확인하였지만 유의적인 효과는 나타나지 않았다(도 4 (B)). In addition, as a result of confirming the amount of change before and after UV irradiation, it was confirmed that the total sample administration group decreased compared to CON, but no significant effect was shown (FIG. 4 (B)).
<1-2> 피부주형의 분석<1-2> Analysis of skin cast
자외선을 조사한 쥐의 등 쪽 피부를 촬영하고 주름 양상의 분석을 위해 주름분석기인 Visioline(VL650; CK electronic GmbH, Germany)를 사용하여 얻은 replica를 이용하여 주름의 면적, 수, 길이, 깊이 등을 확인하였다.The dorsal skin of a rat irradiated with ultraviolet rays was photographed and the area, number, length, depth, etc. of wrinkles were confirmed using the replica obtained using Visioline (VL650; CK electronic GmbH, Germany), a wrinkle analyzer for wrinkle pattern analysis. did
주름 양상 지표를 확인한 결과, 전체 시료 투여군에서 CON 대비 주름의 면적, 길이, 깊이 등 모든 지표에서 감소함을 확인하였고, 시료 투여군 중 UL 및 UH 군에서 그 효과가 보다 우수함을 확인하였다(도 5).As a result of checking the wrinkle pattern index, it was confirmed that all the indicators, such as the area, length, and depth of wrinkles, decreased compared to CON in the entire sample administration group, and the effect was more excellent in the UL and UH groups among the sample administration groups (FIG. 5) .
<1-3> 피부 조직병리학적 분석<1-3> Skin histopathological analysis
실험 종료 후 자외선을 조사한 쥐의 등 쪽 피부를 떼어내어 10%의 포르말린(formalin)에 넣고, 조직병리학적 변화를 확인할 수 있는 헤마톡실린-에오신(hematoxytlin and eosin, H&E), 진피(dermis)에 있는 콜라겐을 확인할 수 있는 면역화학염색(immunohistochemistry, IHC)으로 염색한 후 염색된 조직을 광학현미경(OLYMPUS BX50; OLYMPUS, Japan)으로 이미지화하여 분석하였다.After the end of the experiment, the back skin of the rat irradiated with ultraviolet rays was removed and placed in 10% formalin, and hematoxytlin and eosin (H&E), which can confirm histopathological changes, was applied to the dermis. After staining with immunohistochemistry (IHC), which can confirm the presence of collagen, the stained tissue was imaged and analyzed with an optical microscope (OLYMPUS BX50; OLYMPUS, Japan).
<1-3-1> 표피 두께 변화량 확인<1-3-1> Check the change in epidermal thickness
표피 두께를 확인한 결과, 전체 시료 투여군에서 CON 대비 표피 두께가 감소하는 효과를 확인하였다(도 6).As a result of confirming the epidermal thickness, the effect of reducing the epidermal thickness compared to CON was confirmed in the entire sample administration group (FIG. 6).
<1-3-2> 진피 내 콜라겐 변화량 확인<1-3-2> Check the amount of collagen change in the dermis
콜라겐 비율을 확인한 결과, 전체 시료 투여군에서 CON 대비 콜라겐 비율이 증가하는 효과를 확인하였고, UL 및 UH 군에서 CON 대비 유의적으로 증가함을 확인하였다(도 7).As a result of confirming the collagen ratio, it was confirmed that the effect of increasing the collagen ratio compared to CON in the entire sample administration group, and it was confirmed that it increased significantly compared to CON in the UL and UH groups (FIG. 7).
<1-4> 엘라스틴 변화량 확인<1-4> Check the amount of elastin change
실험 종료 후 자외선을 조사한 쥐의 등 쪽 피부 10 mg 추출한 후, Fastin Elastin assay(F2000; Biocolor, UK)에서 제공하는 방법으로 피부 조직 내 엘라스틴 양을 측정하였다.After the experiment was completed, 10 mg of the dorsal skin of the rat irradiated with ultraviolet light was extracted, and the amount of elastin in the skin tissue was measured by a method provided by Fastin Elastin assay (F2000; Biocolor, UK).
엘라스틴 양을 확인한 결과, 전체 시료 투여군에서 CON 대비 증가하는 효과를 확인하였다(도 8).As a result of confirming the amount of elastin, the effect of increasing compared to CON was confirmed in the entire sample administration group (FIG. 8).
<실험예 2> 피부 관련 유전자 발현 변화량 확인<Experimental Example 2> Confirmation of changes in skin-related gene expression
자외선에 의한 피부보호의 지표로 피부 조직의 탄력과 강도를 유지하는데 주요한 요소인 콜라겐(collagen)의 80 내지 85%를 차지하는 1형 콜라겐(collagen type I, COL1a1)의 분해 효소인 Matrix metalloproteinase(MMP), MMP의 활성을 저해하는 Tissue inhibitor of metalloproteinases(TIMP), 피부 보습인자 히알루론산(hyaluronan)의 가수분해 효소인 히알루로니다제(hyaluronidase, HYAL), 광노화에 의해 생성된 활성산소(ROS)에 의해 활성이 증가되는 전사인자인 NF-kB, 광노화에 영향을 주는 신호 전달 경로인 AKT/mTOR 경로에 관여하는 AKT 1, AKT 2 및 Mammalian target of rapamycin(mTOR)의 유전자 발현량을 qRT-PCR을 이용하여 확인하였다.Matrix metalloproteinase (MMP), an enzyme that decomposes collagen type I (COL1a1), which accounts for 80 to 85% of collagen, which is an indicator of skin protection by ultraviolet rays and is a major factor in maintaining elasticity and strength of skin tissue , Tissue inhibitor of metalloproteinases (TIMP) that inhibits the activity of MMP, hyaluronidase (HYAL), a hydrolytic enzyme of hyaluronan, a skin moisturizing factor, and active oxygen (ROS) generated by photoaging NF-kB, a transcription factor with increased activity,
구체적으로 <실험예 1>의 NOR, CON 및 실험군 UL, UH, EL 및 EM 군의 피부조직을 100 mg 추출한 후, TRIzol(Tri-reagent) 시약을 이용하여 총 RNA를 분리하였다. 분리된 RNA에 50 μM Oligo-(dT) primer와 10 mM dNTP mix를 넣어 65℃에서 5분 동안 반응시킨 후, 5X RT Buffer, 0.1 M DTT, RNaseOUT, SuperScript III, 25 mM MgCl2를 혼합하여 넣고 50℃에서 50분, 85℃에서 5분 동안 반응시켰다. 반응시킨 후 RNase H를 넣고 37℃에서 20분 반응시켜 mRNA로부터 cDNA를 합성하고, PCR을 수행하기 위해 합성한 cDNA 1 μL에 primer 및 SYBR green gene expression master mix와 DEPC water를 혼합한 후 변성(Denaturation)을 위해 50℃에서 2분, 어닐링(annealing)을 위해 90℃에서 10분 및 연장(extension)을 위해 60℃에서 1분 조건에서 50 사이클(cycles)을 수행하였다.Specifically, after extracting 100 mg of the skin tissues of NOR, CON, and experimental groups UL, UH, EL, and EM of <Experimental Example 1>, total RNA was isolated using TRIzol (Tri-reagent) reagent. Add 50 μM Oligo-(dT) primer and 10 mM dNTP mix to the separated RNA, react at 65 ° C for 5 minutes, mix 5X RT Buffer, 0.1 M DTT, RNaseOUT, SuperScript III, and 25 mM MgCl 2 Reacted at 50°C for 50 minutes and at 85°C for 5 minutes. After the reaction, RNase H was added and reacted at 37 ° C for 20 minutes to synthesize cDNA from mRNA. To perform PCR, 1 μL of synthesized cDNA was mixed with primer, SYBR green gene expression master mix, and DEPC water, and then denaturation ), 50 cycles were performed at 50° C. for 2 minutes, annealing at 90° C. for 10 minutes, and extension at 60° C. for 1 minute.
각 target primer 유전자의 발현량은 NOR 그룹 대비 상대적 발현량이다.The expression level of each target primer gene is the relative expression level compared to the NOR group.
<2-1> Matrix metalloproteinase(MMP) 유전자 발현량 확인<2-1> Confirmation of matrix metalloproteinase (MMP) gene expression level
콜라겐 분해효소 MMP 2의 유전자 발현량을 확인한 결과, 전체 시료 투여군에서 CON 대비 유의적으로 감소함을 확인하였고, 시료 투여군 중 UL 및 UH 군에서 그 효과가 보다 우수함을 확인하였다.As a result of confirming the gene expression level of
또한, MMP 3의 유전자 발현량을 확인한 결과, 전체 시료 투여군에서 CON 대비 감소함을 확인하였지만 유의적인 효과는 나타나지 않았다.In addition, as a result of confirming the gene expression level of
또한, MMP 9의 유전자 발현량을 확인한 결과, 전체 시료 투여군에서 CON 대비 감소하는 효과를 확인하였다(도 9).In addition, as a result of confirming the gene expression level of
<2-2> Tissue inhibitor of metalloproteinases(TIMP) 유전자 발현량 확인<2-2> Tissue inhibitor of metalloproteinases (TIMP) gene expression level check
콜라겐 분해효소의 활성을 제해하는 TIMP 1의 유전자 발현량을 확인한 결과, 전체 시료 투여군에서 CON 대비 증가하는 효과를 확인하였고, 시료 투여군 중 UL 및 UH 군에서 그 효과가 보다 우수함을 확인하였다(도 10).As a result of confirming the gene expression level of
또한, TIMP 2의 유전자 발현량을 확인한 결과, 전체 시료 투여군에서 증가하는 효과를 확인하였다(도 10).In addition, as a result of confirming the gene expression level of
<2-3> Collagen typeⅠ(COL1a1) 유전자 발현량 확인<2-3> Confirmation of Collagen type I (COL1a1) gene expression level
콜라겐 생합성 유전자 COL1a1의 발현량을 확인한 결과, 전체 시료 투여군에서 CON 대비 증가하는 효과를 확인하였고, 시료 투여군 중 UL 군에서 그 효과가 가장 우수함을 확인하였다(도 11). As a result of confirming the expression level of the collagen biosynthesis gene COL1a1, it was confirmed that the effect increased compared to CON in the entire sample administration group, and the effect was the most excellent in the UL group among the sample administration groups (FIG. 11).
<2-4> Hyaluronidase(HYAL) 유전자 발현량 확인<2-4> Confirmation of hyaluronidase (HYAL) gene expression level
피부 보습인자 히알루론산의 분해 효소 HYAL의 유전자 발현량을 확인한 결과, 전체 시료군에서 CON 대비 감소하는 효과를 확인하였고, UH를 제외한 전체 시료군에서 CON 대비 유의적으로 감소함을 확인하였다(도 12).As a result of confirming the gene expression level of HYAL, a degrading enzyme of hyaluronic acid, a skin moisturizing factor, it was confirmed that the effect of decreasing compared to CON was confirmed in the entire sample group, and it was confirmed that it was significantly reduced compared to CON in all sample groups except for UH (FIG. 12 ).
<2-5> NF-kB 유전자 발현량 확인<2-5> Confirmation of NF-kB gene expression level
염증 유발 관련 인자 NF-kB의 유전자 발현량을 확인한 결과, 전체 시료군에서 CON 대비 감소하는 효과를 확인하였다(도 13).As a result of confirming the gene expression level of the inflammation-related factor NF-kB, the effect of decreasing compared to CON was confirmed in the entire sample group (FIG. 13).
<2-6> AKT(protein kinase B) 및 Mammalian target of rapamycin(mTOR) 유전자 발현량 확인<2-6> Confirmation of AKT (protein kinase B) and Mammalian target of rapamycin (mTOR) gene expression
자외선에 의해 활성화되어 광노화에 영향을 주는 AKT/mTOR 경로와 관련된 AKT 1 유전자 발현량을 확인한 결과, 전체 시료군에서 CON 대비 감소하는 효과를 확인하였다(도 14 (A)).As a result of confirming the expression level of the
또한 AKT 2의 유전자 발현량을 확인한 결과, 전체 시료군에서 CON 대비 감소하는 효과를 확인하였다(도 14 (B)).In addition, as a result of confirming the gene expression level of
또한 mTOR 유전자 발현량을 확인한 결과, 전체 시료군에서 CON 대비 감소하는 효과를 확인하였다(도 14 (C)).In addition, as a result of confirming the mTOR gene expression level, the effect of decreasing compared to CON was confirmed in the entire sample group (FIG. 14 (C)).
<실험예 3> 염증인자 단백질 발현 변화량 확인<Experimental Example 3> Confirmation of inflammatory factor protein expression change
자외선에 의해 증가되는 염증인자 단백질인 p-JNK, p-ERK 및 p-p38의 발현량을 웨스턴 블로팅법(Western blotting)을 이용하여 확인하였다.The expression levels of p-JNK, p-ERK, and p-p38, which are inflammatory factor proteins increased by ultraviolet light, were confirmed using Western blotting.
구체적으로 <실험예 1>의 NOR, CON 및 실험군 UL, UH, EL 및 EM 군의 피부조직으로부터 얻은 단백질 용해물(lysate) 25 μg을 SDS-PAGE 방법을 통해 총 단백질을 PVDF 멤브레인(polyvinylidene fluoride membrane)로부터 전사시킨 후 염증 관련 단백질에 특이적인 1차 항체(phosphorylated extracellular signal regulated kinase;p-ERK, phosphorylated c-Jun N-terminal kinase;p-JNK, phosphorylated p38;p-p38)로 24시간 동안 반응시켰다. 반응된 단백질을 겨자무과산화효소(Horseradish peroxidase, 1:2000)로 컨쥬게이션 된 2차 항체로 1시간 반응시킨 후 TBST(tris buffer saline tween 20) 버퍼로 5번 린스하고 ELC(enhanced chemiluminescence)로 발색하였다. 발색 후 LAS image sofrware(Fuji, New York, NY)로 p-ERK, p-JNK 및 p-p38의 단백질 양을 측정하였다. 각 단백질 발현량 수치는 GAPDH 대비 상대적인 발현량으로 확인하였다.Specifically, 25 μg of protein lysate obtained from the skin tissue of NOR, CON, and experimental groups UL, UH, EL, and EM of <Experimental Example 1> was subjected to SDS-PAGE to measure total protein on a PVDF membrane (polyvinylidene fluoride membrane). ) and reacted with primary antibodies specific for inflammation-related proteins (phosphorylated extracellular signal regulated kinase; p-ERK, phosphorylated c-Jun N-terminal kinase; p-JNK, phosphorylated p38; p-p38) for 24 hours made it The reacted protein was reacted with a secondary antibody conjugated to horseradish peroxidase (1:2000) for 1 hour, rinsed 5 times with TBST (tris buffer saline tween 20) buffer, and developed by ELC (enhanced chemiluminescence) did After color development, the protein amounts of p-ERK, p-JNK, and p-p38 were measured using LAS image software (Fuji, New York, NY). Each protein expression level was confirmed as a relative expression level compared to GAPDH.
p-ERK 단백질 발현량을 확인한 결과, 전체 시료군에서 CON 대비 유의적인 효과는 나타나지 않았다(도 15 (A)).As a result of confirming the p-ERK protein expression level, there was no significant effect compared to CON in the entire sample group (FIG. 15 (A)).
또한 p-JNK 단백질 발현량을 확인한 결과, 전체 시료군에서 CON 대비 유의적인 효과는 나타나지 않았다(도 15 (B)).In addition, as a result of confirming the p-JNK protein expression level, no significant effect was found compared to CON in the entire sample group (FIG. 15 (B)).
또한 p-p38 단백질 발현량을 확인한 결과, 전체 시료군에서 CON 대비 감소하는 효과를 확인하였고, EL을 제외한 전체 시료군에서 CON 대비 유의적으로 감소함을 확인하였고, 시료 투여군 중 UL 군에서 그 효과가 가장 우수함을 확인하였다다(도 15 (C)).In addition, as a result of confirming the p-p38 protein expression level, the effect of decreasing compared to CON was confirmed in the entire sample group, and it was confirmed that it was significantly reduced compared to CON in all sample groups except EL, and the effect was confirmed in the UL group among the sample administration groups It was confirmed that was the best (FIG. 15 (C)).
<실험예 4> 염증인자 사이토카인(Cytokine) 함량 확인<Experimental Example 4> Confirmation of inflammatory factor cytokine content
자외선에 의해 증가되는 염증성 사이토카인인 인터류킨-6(Interleukin-6, IL-6), 인터류킨-12(Interleukin-12, IL-12) 및 종양괴사인자-α(tumor necrosis factor-α, TNF-α)의 함량을 ELISA kit(BD Bioscience, San Jose, CA)를 이용하여 확인하였다.Interleukin-6 (IL-6), Interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α), which are inflammatory cytokines increased by ultraviolet light ) was confirmed using an ELISA kit (BD Bioscience, San Jose, CA).
구체적으로 <실험예 1>의 NOR, CON 및 실험군 UL, UH, EL 및 EM 군의 피부조직을 추출한 후, 단백질 정량법(BCA)으로 단백질 양을 분석하고 단백질 mg 당 함량으로 사이토카인(IL-6, IL-12 및 TNF-α)의 함량을 확인하였다.Specifically, after extracting the skin tissues of the NOR, CON, and experimental groups UL, UH, EL, and EM groups of <Experimental Example 1>, the amount of protein was analyzed by protein quantification method (BCA), and the cytokine (IL-6 , IL-12 and TNF-α) contents were confirmed.
IL-6 발현량을 확인한 결과, 전체 시료군에서 CON 대비 유의적으로 감소하는 효과를 확인하였다(도 16 (A)).As a result of confirming the IL-6 expression level, a significant decrease compared to CON was confirmed in the entire sample group (FIG. 16 (A)).
또한 IL-12 발현량을 확인한 결과, 전체 시료군에서 CON 대비 유의적으로 감소하는 효과를 확인하였다(도 16 (B)).In addition, as a result of confirming the IL-12 expression level, a significant decrease compared to CON was confirmed in the entire sample group (FIG. 16 (B)).
또한 TNF-α 발현량을 확인한 결과, 전체 시료군에서 CON 대비 유의적으로 감소하는 효과를 확인하였다(도 16 (C)). In addition, as a result of confirming the TNF-α expression level, it was confirmed that the effect of significantly decreasing compared to CON in the entire sample group (FIG. 16 (C)).
<실험예 5> 단쇄지방산(short-chain fatty acid, SCFA) 함량 확인<Experimental Example 5> Confirmation of short-chain fatty acid (SCFA) content
단쇄지방산인 아세트산, 프로피온산, 부티르산, 발레르산 및 총 단쇄지방산의 함량을 기체 크로마토그래피(Gas chromatography, GC)로 확인하였다.The contents of short-chain fatty acids such as acetic acid, propionic acid, butyric acid, valeric acid, and total short-chain fatty acids were confirmed by gas chromatography (GC).
구체적으로 <실험예 1>의 NOR, CON 및 실험군 UL, UH, EL 및 EM 군의 맹장을 적출하고 메탄올로 추출한 후, 추출물을 GC컬럼(DB-FFAP 123-3253, 50 m×0.32 mm×0.50 μM)이 장착된, 컬럼 온도를 100℃에서 1분 유지한 후, 180℃까지 8℃/min 속도로 증가시킨 다음, 200℃까지 20℃/min 속도로 증가시킨 후 200℃에서 5분으로 정체되도록 설정한 GC(Agilent Technologies, CA, USA)를 이용하여 SCFA 함량을 확인하였다.Specifically, after extracting the cecum of the NOR, CON, and experimental groups UL, UH, EL, and EM groups of <Experimental Example 1> and extracting with methanol, the extract was placed on a GC column (DB-FFAP 123-3253, 50 m × 0.32 mm × 0.50 μM), the column temperature was maintained at 100 °C for 1 min, then increased at a rate of 8 °C/min to 180 °C, then increased at a rate of 20 °C/min to 200 °C, then plateaued at 200 °C for 5 min. The SCFA content was confirmed using GC (Agilent Technologies, CA, USA) set to be.
아세트산 함량을 확인한 결과, UL 군에서 CON 대비 증가하는 효과를 확인하였다(도 17 (a)).As a result of confirming the acetic acid content, the effect of increasing compared to CON was confirmed in the UL group (FIG. 17 (a)).
또한 프로피온산 함량을 확인한 결과, 전체 시료군에서 CON 대비 유의적인 차이를 보이자 않음을 확인하였다(도 17 (B)).In addition, as a result of confirming the propionic acid content, it was confirmed that there was no significant difference compared to CON in the entire sample group (FIG. 17 (B)).
또한 부티르산 함량을 확인한 결과, 전체 시료군에서 CON 대비 증가하는 효과를 확인하였고, UL 군에서 유의적으로 증가함을 확인하였다(도 17 (C)).In addition, as a result of confirming the butyric acid content, the effect of increasing compared to CON was confirmed in the entire sample group, and it was confirmed that it increased significantly in the UL group (FIG. 17 (C)).
또한 발레르산 함량을 확인한 결과, 전체 시료군에서 EL 군에서 증가하는 효과를 확인하였다(도 17 (D)).In addition, as a result of confirming the valeric acid content, an increasing effect was confirmed in the EL group in the entire sample group (FIG. 17 (D)).
또한 총 단쇄지방산 함량을 확인한 결과, UL, UH 및 EL 군에서 증가하는 효과를 확인하였다(도 17 (E)).In addition, as a result of confirming the total short-chain fatty acid content, an increasing effect was confirmed in the UL, UH, and EL groups (FIG. 17 (E)).
결론적으로, 들쭉나무 열매 분말 또는 추출물 분말을 섭취하였을 때 수분보유량 증가, 경피수분손실량 감소, 피부 두께 감소, 홍반수치 감소, 피부 두께 및 주름 감소, 표피 두께 감소, 콜라겐 비율 증가 및 엘라스틴 양 증가 효과를 확인하여 자외선으로 인해 저하된 피부 장벽 기능에 도움을 줄 수 있음을 확인하였다.In conclusion, the effect of increasing water retention, reducing transepidermal water loss, reducing skin thickness, reducing erythema, reducing skin thickness and wrinkles, reducing epidermal thickness, increasing collagen ratio, and increasing elastin amount when blueberry fruit powder or extract powder was ingested It was confirmed that it could help the reduced skin barrier function due to ultraviolet rays.
또한, 피부 관련 유전자인 콜라겐 분해 효소(MMP 2, MMP 3 및 MMP 9)의 발현량 감소, 콜라겐 분해효소 활성 저해 유전자(TIMP 1 및 TIMP 2)의 발현량 증가, 콜라겐 생합성 유전자(COL1a1)의 발현량 증가 및 피부 보습인자 히알루론산의 분해효소(HYAL)의 발현량 감소 효과를 확인하여 피부노화 개선에 도움을 줄 수 있음을 확인하였다.In addition, the expression of skin-related genes, collagen degrading enzymes (
또한, 염증 유발 관련 인자(NF-kB)의 발현량 감소, 광노화에 영향을 주는 AKT/mTOR 경로 관련 인자(AKT 1, AKT 2) 발현량 감소, 염증인자 단백질(p-p38)의 발현량 감소 및 염증인자 사이토카인(IL-6, IL-12, TNF-α)의 함량 감소 효과를 확인하여 자외선에 의한 피부 염증 반응을 감소시킬 수 있음을 확인하였다.In addition, the expression level of inflammation-inducing factor (NF-kB) decreased, the expression level of AKT/mTOR pathway related factors (
또한, 단쇄지방산(아세트산, 부티르산, 발레르산, 총 단쇄지방산)의 함량이 증가함을 확인하여 광노화로 인한 단쇄지방산 감소를 개선할 수 있음을 확인하였다.In addition, it was confirmed that the decrease in short-chain fatty acids due to photoaging could be improved by confirming that the content of short-chain fatty acids (acetic acid, butyric acid, valeric acid, and total short-chain fatty acids) increased.
또한, <실시예 1> 및 <비교예 1>에서 제조한 들쭉나무 열매 분말 또는 추출물 분말의 피부노화 개선 효과를 비교한 결과, 들쭉나무 열매 분말이 들쭉나무 열매 추출물 분말보다 저농도에서 우수한 효과를 나타냄을 확인하였다. In addition, as a result of comparing the skin aging improvement effects of the blueberry fruit powder or extract powder prepared in <Example 1> and <Comparative Example 1>, the blueberry fruit powder showed a superior effect at a lower concentration than the blueberry fruit extract powder. confirmed.
Claims (11)
Blueberry tree ( Vaccinium uliginosum ) A composition for improving skin wrinkles caused by ultraviolet rays, containing fruit powder as an active ingredient.
들쭉나무 열매 분말은 들쭉나무 열매 건조물을 분쇄하여 제조한, 자외선으로 유발되는 피부 주름 개선용 조성물.
According to claim 1,
Blueberry fruit powder is a composition for improving skin wrinkles caused by ultraviolet rays, prepared by pulverizing dried blueberry fruit.
상기 분말은 콜라겐 함량 증가, 엘라스틴 함량 증가, 히알루론산 함량 증가, 염증관련 인자 감소, 염증인자 단백질 감소, 염증인자 사이토카인 감소 및 AKT/mTOR 경로 관련 인자 감소 중 어느 하나 이상의 특징을 갖는, 자외선으로 유발되는 피부 주름 개선용 조성물.
According to claim 1,
The powder has an increase in collagen content, an increase in elastin content, an increase in hyaluronic acid content, a decrease in inflammation-related factors, a decrease in inflammatory factor proteins, a decrease in inflammatory factor cytokines, and a decrease in AKT/mTOR pathway related factors. A composition for improving skin wrinkles.
상기 분말이 단쇄지방산(short-chain fatty acid, SCFA) 함량을 증가시키는 것인, 자외선으로 유발되는 피부 주름 개선용 조성물.
According to claim 1,
The composition for improving skin wrinkles caused by ultraviolet rays, wherein the powder increases the content of short-chain fatty acid (SCFA).
상기 단쇄지방산은 포름산(Formic acid), 아세트산(Acetic acid), 프로피온산(Propionic acid), 부티르산(Butyric acid), 아이소부티르산(Isobutyric acid), 발레르산(Valeric acid) 및 아이소발레르산(Isovaleric acid)으로 구성된 군에서 선택된 하나 이상인, 자외선으로 유발되는 피부 주름 개선용 조성물.
According to claim 4,
The short chain fatty acids include formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid and isovaleric acid. At least one selected from the group consisting of, a composition for improving skin wrinkles caused by ultraviolet rays.
화장료 첨가제를 포함하는, 자외선으로 유발되는 피부 주름 개선용 화장료 조성물.
blueberry ( Vaccinium uliginosum ) fruit powder; and
A cosmetic composition for improving skin wrinkles caused by ultraviolet rays, comprising a cosmetic additive.
화장료 첨가제는 미백제, 보습제, 항염증제, 항박테리아제, 항진균제, 비타민. 자외선 차단제, 항생제, 여드름 방지제, 향수 및 염료으로 구성된 군에서 선택된 하나 이상인, 자외선으로 유발되는 피부 주름 개선용 화장료 조성물.
According to claim 6,
Cosmetic additives are whitening agents, moisturizing agents, anti-inflammatory agents, antibacterial agents, antifungal agents, vitamins. A cosmetic composition for improving skin wrinkles caused by ultraviolet rays, which is at least one selected from the group consisting of sunscreens, antibiotics, anti-acne agents, perfumes and dyes.
약제학적으로 허용되는 담체를 포함하는, 자외선으로 유발되는 피부 주름 개선용 약제학적 조성물.
blueberry ( Vaccinium uliginosum ) fruit powder; and
A pharmaceutical composition for improving skin wrinkles caused by ultraviolet rays, comprising a pharmaceutically acceptable carrier.
약제학적으로 허용되는 담체는, 약제학적으로 허용되는 첨가제, 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제, 희석제 및 부형제으로 구성된 군에서 선택된 하나 이상인, 자외선으로 유발되는 피부 주름 개선용 약제학적 조성물.
According to claim 8,
Pharmaceutically acceptable carriers are pharmaceutically acceptable additives, fillers, extenders, binders, wetting agents, disintegrants, surfactants, diluents, and excipients, which are one or more selected from the group consisting of pharmaceutical agents for improving skin wrinkles caused by ultraviolet rays. composition.
식품학적으로 허용되는 식품첨가제를 포함하는, 자외선으로 유발되는 피부 주름 개선용 건강식품.
blueberry ( Vaccinium uliginosum ) fruit powder; and
A health food for improving skin wrinkles caused by ultraviolet rays, including a food additive acceptable in food science.
식품첨가제는 천연 탄수화물, 향미제, 교정제, 영양제, 비타민, 전해질, 풍미제, 착색제, 중진제, 안정화제, 방부제 및 탄산화제로 구성된 군에서 선택된 하나 이상인, 자외선으로 유발되는 피부 주름 개선용 건강식품.
According to claim 10,
Food additives are at least one selected from the group consisting of natural carbohydrates, flavoring agents, corrective agents, nutrients, vitamins, electrolytes, flavoring agents, coloring agents, intensifiers, stabilizers, preservatives, and carbonation agents for improving skin wrinkles caused by ultraviolet rays. food.
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백두산 야생 '들쭉', 항산화 성분 '듬뿍'(2009.08.25.) 1부.* |
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