1、防曬、美白、抗老化,趙曉秋醫師成大醫院皮膚科,皮膚的老化,皮膚慢慢失去了光澤、粗糙萎縮、沒有彈性、皺紋增加黑色素細胞調節失常，黑斑、色素脫失、皮膚異色症會出現,Causes of skin aging,30 yr/o,40 yr/o,60 yr/o and over,WRINKLES,LOSS OF FIRMNESS,SPOTS,DRYNESSPRURITUS,50 yr/o,CAUSE N1,menopause,CAUSE N2,AND AGGRAVIATING FACTORS,UVA rays,Genetic and hormonalaging,EnvironmentNutritionLi
2、festyle (smoking, alcohol)Stress,Why Does the Skin Age?,皮膚光反應類型,紫外線的分類,依照它們的波長、穿透力以及對人體皮膚所造成的影響或傷害UVA (波長320-400nm)UVB (波長280-320 nm)UVC (波長200-280 nm),UVA,隱形的殺手，因為它看不到、穿透力又強，可以透過雲層、穿過玻璃造成皮膚老化的主因,UVB,主要造成急性的傷害晒傷亦具有累積的作用，長期曝晒也會造成皮膚的老化及皮膚癌,UVC,對人體造成的傷害性最大已被地球外圍的臭氧層過濾掉臭氧層每減少 1，人類的皮膚癌比例就會上升 2。自1900年以來，地
3、球上的臭氧層至少已經減少了2530。也就是說，人類罹患皮膚癌機率提高了將近60,日照與皮膚之變化,短波,中波,長波,UVC,UVB,UVA,皮 膚 癌,皮 膚 老 化,色 素 沉 澱,晒 傷,200,290,320,400,Treatment of Photoaging,延遲皮膚的老化,最好的方法是盡量防止污染及陽光的傷害預防勝於治療，好好的保養皮膚，比使用各種物理性或化學性的治療為好,皮膚老化的預防,超完美防曬,Commonly used ingredients in sunscreen,認識SPF (Sun Protection Factor) 防曬係數,針對UVB(曬紅)的防護能力SPF
4、=使用防曬產品曬紅時間/未使用防曬產品曬紅時間例:10分鐘曬紅，則SPF15 =曬紅時間減慢15倍=150分鐘曬紅=防曬時間150分鐘SPF15防曬品可過濾94%的UVBSPF30 可過濾超過97%的UVB皮膚的防曬乳液厚度為每平方公分兩毫克（2 /2）,UVA防曬係數,PA (UVA防曬指數) 日本系統IPD 立即預防曬黑反應(立即性色素沉著指數)PPD (持續性色素沉著指數）PA+=PPD24PA+=PPD46PA+=PPD68美國皮膚科醫學會建議廣效性防曬產品必須隔離370nm以上光波，PPD4 或 PA+,UV Protection Factor (UPF),用來標示衣物阻擋UV的能力
5、 Good protection (UPF 15-24) 93.3 - 95.9 % UV radiation Blocked Very good protection (UPF 25-39) 96.0 - 97.4 % UV radiation Blocked Excellent protection (UPF 40-50+) 97.5 or more % UV radiation Blocked,紫外線指數 (UVI, UV Index),每小時的累積量100J/m2=1 UVI中午陽光最強的一個小時，紫外線到達地面的輻射量0-2: 微量級3-4: 低量級5-6: 中等級7-9: 過量級1
6、0-15: 危險級指數10以上，東方人只要曬10至20分鐘，皮膚就會曬紅,紫外線防護措施,常見的防曬品重要標示,Hypoallergic (低敏感性)Noncomedogenic (不會造成粉刺)Sweatproof (抗汗)Water resistant確保下水後20分鐘內都還有防曬效果Very water resistant確保下水後80分鐘內都還有防曬效果,理想的太陽眼鏡,必須能濾去百分九十六以上的紫外線，才能避免因紫外線造成的白內障讓百分之四十以上的可見光透過,防晒唇膏,嘴唇尤其是下唇 長期在陽光下曝曬， 也必須使用防晒唇膏保護主要成分：蠟 蜜蠟、巴西蠟(Carnauba wax)、燈
7、心草蠟(Candelilla wax)、白地蠟油 礦物油、凡士林或植物油 -荷荷巴油、葡萄仔油、巴西核果油色料 天然與合成著色劑,防曬產品的使用方法,出門前15至30分鐘使用防曬品，讓皮膚充分接觸吸收。正確的塗抹方式：將足量防曬品擠在指頭上，再塗抹在臉部皮膚，另外不要忘了塗抹鼻子、嘴唇、頸背及耳朵。,善用防曬乳液紫外線可以穿透玻璃、水面達60公分深，所以游泳時要塗上防水性(water-resistant)的防曬產品。在雪地或是沙灘，紫外線會經由反射或折射到達體表。高山比平地紫外線強，每增高300公尺，紫外線強度增加8-10%。,正確的防曬觀念,什麼是好的防晒品,基質要和皮膚性質配合，不太油膩、
8、不過於鹼性，保濕力夠低敏感性標示清楚的化學成份、製造日期、有效期限同時防禦UVA及UVB,沒有適合每一個人的防晒產品，也沒有最好的防晒產品。視自己的需要選用適合自己的產品,遠離紫外線五部曲,年輕的肌膚也要防曬因為肌膚細嫩，所以更需要特別的呵護防曬不分男女不是要美白，而是怕得癌！防曬不分晴天雨天防曬是一種基本的保養，不分四季晴雨陽光最強時避免外出防曬用品並非是萬靈丹避免直接暴露,皮膚的構造-表皮,角質層、透明層、顆粒層、棘狀層、基底層基底層：製造表皮的工廠，分裂、增殖、往上移行，皮膚再生，修復受傷皮膚黑色素細胞：製造黑色素、決定人的膚色、防晒、產生黑斑角質層：皮膚最表面部份、含有油脂膜和一定量的
9、水份、保護皮膚抵抗微生物、化學物質防止水份、電解質流失，維持體內環境恆定,皮膚的構造-真皮,血管：溫度調節， 維持恆溫淋巴管神經：感覺冷熱痛癢汗腺：分泌汗液、散熱皮脂腺：分泌油脂、潤滑皮膚毛髮平滑肌纖維組織,皮膚的構造-皮下組織,脂肪組織富有彈性，具緩衝作用儲存能量,皮膚的功能,物理屏障分泌汗液、調節體溫、血壓感覺冷熱痛癢再生能力、免疫功能個人特徵吸收作用反應身體狀況,皮膚的生理,酸鹼值弱酸, pH 4.5-6.5含水量皮脂量經皮水份喪失皮膚的屏障亮度及彩度彈性皮膚老化,使用膠原蛋白細緻霜前皮膚含水量 90,天然的保養品真的比較好？,天然的保養品有兩大類：動物萃取物胎盤素、膠原素、彈性纖維蛋白
10、、血清植物萃取物蘆薈、海藻、小麥胚芽、酪梨、大豆卵磷脂、蛋黃素、胡蘿蔔素、百合一般擦在表皮的藥物其分子量必須在三千以下，才會被皮膚所吸收；且天然的保養品中某一種具有神奇療效的成份，一般而言其含量都很低，若無特殊的提煉濃縮，也無法達到療效。切記天然的保養品也會產生過敏給您的建議適合您的就是最好的保養品，自然的、人工合成的都一樣,Tyrosine（酪胺酸）- DOPA（多巴） - DOPA - Melanin Tyrosinase （酪胺酸酵素）,Pigmentation Pathway,Pigmentation Pathway,Melanin生產線:多階段的化學作用，主要推手是酵素Tyrosin
11、aseMelanin的包裝:以Melanosome存於Melanocyte，並輸出至緊鄰的角質細胞 (Keratinocyte)戰略伙伴:表皮兩強-Melanocyte 和Keratinocyte。是戰略伙伴，形成所謂的Epidermal Melanin Unit (表皮黑色素單位)皮膚黑白不在於Melanocyte的多少，而在產生Melanin的能力及Melanosome 的成熟度。,Skin Lightening,SunprotectionDepigmenting agents Laser,Depigmenting agents,Work best when melanosis or me
12、lanocytosis is restricted to the epidermiscan be divided into several groups:Phenolic compounds Hydroquinone 4-Methoxyphenol 4-Hydroxyanisol Nonphenolic compounds Corticosteroids Tretinoin Azelaic acid N-acetylcysteineL-ascorbyl-2-phosphate Kojic acid Combination formulas Kligmans formula,Hydroquino
13、nes (對苯二酚，美白),其美白機理，是凝結酪氨酸酵素，並行黑色素的破壞其美白效果非常顯著，但是塗擦的範圍，多數人會有明顯的紅斑出現對苯二酚的副作用並非只是局部發紅，若濃度超過5%時，會引起皮膚吸收的全身性作用，過去曾有引發白斑症的例子出現,Hydroquinone,Improvement with HQ (monotherapy) is usually observed at 4-6 weeksPlateau at approximately 4 months,Arbutin熊果素,結構與對苯二酚相似，經皮膚吸收後，會被水解成對苯二酚跟一分子的葡萄糖，因此，它的作用機轉與對苯二酚雷同,越橘
14、科植物熊果葉,Retinoids,調節表皮細胞分化，對細紋、色素斑點和毛孔粗大有療效維他命A具有保護皮膚與黏膜表皮細胞的作用維他命A是以A酯、A醇、A醛、A酸幾種形式存在於人體，真正有防老作用的是A酸,Combination formulas,Kligman formula (克里曼處方 ): in a hydrophilic ointment base 5% HQ0.1% retinoic acid0.1% dexamethasoneTri-Luma (汰膚斑): in a cream formulation0.01% fluocinolone4% HQ0.05% tretinoin,Koj
15、ic Acid (麴酸),其美白機理是螯合銅離子，使無法形成酪氨酸酵素因為安全，所以在美白的用量上並無限制，但麴酸不穩定，易變色，因此也添加了許多的抗氧化劑及紫外線吸收劑於配方中 a competitive and reversible inhibitor of animal and plant polyphenol oxidases, xanthine oxidase, and D- and some L-amino acid oxidases. 長期使用麴酸會造成細胞病變毒化（？）Food Chem Toxicol. 2004 Jan;42(1):93-105.,Azelaic acid
16、(杜鵑花酸),學名是壬二酸，是一個九個碳的分子杜鵑花酸與杜鵑花(Azalea)一點也沾不上關係，只是湊巧英文拼音類似而已。是汗斑菌(Pityrosporum ovale)的代謝產物之一；被汗斑菌感染的病人皮膚常會變白抑制tyrosinase活性治療粉刺效果100%，丘疹、膿皰的效果65%,Paper Mulberry (構樹),5-(3-2,4-dihydroxyphenylpropyl)-3,4-bis (3-methyl-2-butenyl)-1,2-benzenediolFrom paper mulberry root barkTyrosinase inhibitorScavenge f
17、ree radicalsThe concentration causing 50% inhibition of the activity of tyrosinase0.396% paper mulberry5.5% for HQ10.0% for kojic acid 1% paper mulberry extractNo irritation or sensitization,Thioctic Acid (-Lipoic Acid, -硫辛酸 ),Disulfide derivative of octanoic acid ROS scavenger and redox regulator I
18、nhibits tyrosinase activity probably by chelating the copper ions,Unsaturated Fatty Acids,Oleic acid (C18:1), linoleic acid (C18:2), and -linolenic acid (C18:3) suppress pigmentation in vitro Linoleic acid accelerates the degradation of tyrosinase, inhibiting melanogenesis,Glabridin 甘草黃酮 (Licorice e
19、xtract,甘草萃取),The active agents: liquiritin and isoliquertinLiquiritin induces skin lightening by dispersing melaninInhibited tyrosinase activity of melanocytes without cytotoxicityInhibition of superoxide anion production and cyclooxygenase activityUV-Binduced pigmentation and erythema were Inhibite
20、d by topical application of 0.5% glabridin 0.4% licorice extract + 0.05% betamethasone + 0.05% retinoic acid,Aleosin 蘆薈素,From the aloe vera plantInhibit tyrosinase by competitive inhibition at the dihydroxyphenylalanine oxidation siteLimited ability to penetrate the skin because of its hydrophilic n
21、ature,維他命C 的作用,促進膠原蛋白生成：參與lysin及proline的氫氧化反應，促進procollagen形成collagen清除自由基：防止皮膚受損老化光防護作用(photoprotection)：抵抗UVA、UVB所造成的傷害還原黑色素達到美白的效果防止紫外線造成免疫抑制,促進膠原再生,抗氧化,幫助傷口癒合,抗壞血酸,幫助鐵質的吸收,c,對抗病毒、預防並治療感冒,強化身體的防禦能力,人體緊張時，維他命C的消耗量會增加,維他命C,人一天所需的維他命C是70-75毫克，口服維他命只有百分之七的量會到達血管末梢的皮膚，直接塗抹劑發揮到深層的量也很有限離子導入超音波導入,維他命C產品配
22、方之穩定性,Soybean trypsin inhibitor,3 weeks of raw soy milk applicationInhibits the activation of protease activated receptor-2 pathway (PAR-2): reversiblea pathway necessary for keratinocyte phagocytosis of melanosomes and melanosome transfer,N-acetyl glucosamine,Inhibits the glycosylation of tyrosinas
23、e2% N-acetyl glucosamine applied twice daily for 8 weeks in a cosmeceutical moisturizer showed modest pigment lighteningNAG 2% + niacinamide 4% formulation,Tranexamic acid (傳明酸),衛生署許可最高濃度3%抑制tyrosinase activity,Chamomile ET (洋甘菊萃取),衛生署許可最高濃度0.5%抑制內皮素(endothelin)抗發炎,Ellagic Acid (鞣花酸),衛生署許可最高濃度0.5%屬多
24、酚的一種其美白機理是螯合銅離子，使使酪氨酸酵素不活化,化學換膚,非常淺層,淺層,中層,深層,角質層,表皮層,真皮層,果酸的化學結構,依氫氧基(OH)在化學結構中的位置-hyroxy acid (AHA)甘醇酸 (glycolic acid)乳酸 (lactic acid)酒石酸 (tartaric acid)-hydroxy acid (BHA)水楊酸 (salicylic acid),-hydroxy acid (ABHA)蘋果酸 (malic acid)檸檬酸 (citric acid),-Hydroxy acids,Act as chelators (calcium ions), red
25、uce epidermal calcium ions cause a loss of calcium ions from the cadherins of the desmosomes and adherens junctionsDisruption of cell adhesion and desquamationPromote cell growth and retard cell differentiationIncreease type I collagen mRNA and hyaluronic acid content in human skin,Alpha-hydroxy aci
26、ds (果酸 甘醇酸、乳酸),並無直接美白作用，可促進角質細胞代謝，可間接協助美白 AHA家族包括有檸檬酸、蘋果酸、乳酸、甘醇酸、酒石酸等 從甘蔗中提取的甘醇酸，因為分子量小、吸收穩定，最常用在護膚、換膚果酸的作用乃在去除過度角化的角質層，同時促進真皮層內膠原纖維，粘多醣蛋白的增生，所以對於日光傷害的皮膚及青春痘、皺紋、黑斑、老人斑及粗糙的肌膚有改善的效果,市售果酸與醫療院所果酸,不同果酸濃度的效用10% ：表皮層增厚，促進真皮層內彈性纖維增生治痘、除痘疤、抗皺、縮小毛孔、改善粗糙皮膚市售保養品：法律規定15%醫療院所：20-70%安全性的問題,不適合做果酸換膚者,有會擴散的傳染性皮膚病病毒疣
27、、正在發作的單純皰疹正有皮膚病濕疹、紅斑性狼瘡敏感性膚質酒糟、孕婦白斑患者,Beta-Hydroxy Acids (BHA) (柔酸, salicylic acid),BHA又稱水楊酸是從水楊木提煉出來的一種物質對祛除皮膚表層暗啞老化細胞及防止和淡化色斑和色素沉著效果顯著 衛生署藥政處將化妝品所含的水楊酸濃度限制在0.2-1.5%之間，以確定長期使用的安全性,植酸（Phytic acid, Inositol hexaphosphate, IP6）,來自豆類或稻、麥等穀皮的化合物被認為具有對抗癌症的作用，在美國以錠劑的口服保健食品為主 (phytic acid had anti-neoplast
28、ic properties in breast, colon, liver, leukemia, prostate, sarcomas, and skin cancer; Complement Ther Med. 2002 Dec;10(4):229-34. )Topical application of IP6: inhibited skin tumor development significantly in a dose-dependent manner (Nutr Cancer. 2003;46:66-72 )造成角質層的自然剝落與更新及抑制酪氨酸脢等效果,常用的抗老化產品及治療,Re
29、tinoids,調節表皮細胞分化，對細紋、色素斑點和毛孔粗大有療效維他命A具有保護皮膚與黏膜表皮細胞的作用維他命A是以A酯、A醇、A醛、A酸幾種形式存在於人體，真正有防老作用的是A酸,Retinoids,0.05% tretinoin and isotretinion: improve fine and coarse wrinkling and lighten actinic lentigins and mottled hyperpigmentation (36-weeks period) Compaction of the stratum corneum Epidermal hyperpla
30、sia Correction of atypia Dispersion of melanin granules Increased dermal collagen synthesis Angiogenesis,Retinoid dermatitisoccur within first month of treatment,ErythemaScalingPruritusBurningStiningDryness,Kinerase 凱娜詩,Kinerase的主要成份是N6-furfuryladenine (Kinetin, 凱因庭)0.1% N6-furfuryladenine有下列優點效力與維他
31、命A酸(Retinoids)相同，可以減少細皺紋沒有刺激性，可以用在最敏感皮膚，即使有Rosacea或異位性皮膚都可以用有很好的保濕作用長期使用會減輕皮膚黑斑，雀斑的顏色,Biochem Biophys Res Commun. 15;201(2):665-72, 1994.,Antioxidants,Limited efficiency of sunscreensNo one product provides excellent protection over the whole UVA range (320-400 nm)Most people apply sunscreen 0.5 mg/
32、cm2UV-induced DNA damage and immunosuppression are still present at suberythemal levels of irradiationComponents of sunscreens and their photoproducts: free radicals,維他命C 的作用,促進膠原蛋白生成：參與lysin及proline的氫氧化反應，促進procollagen形成collagen清除自由基：防止皮膚受損老化光防護作用(photoprotection)：抵抗UVA、UVB所造成的傷害還原黑色素達到美白的效果防止紫外線造成
33、免疫抑制,維他命C,人一天所需的維他命C是70-75毫克，口服維他命只有百分之七的量會到達血管末梢的皮膚，直接塗抹劑發揮到深層的量也很有限離子導入超音波導入,Vitamin E (Tocopherols),90% of tissue Vit E:- tocopherolTopical - tocopherol Prevent UV-induced free radical formation Protect endogenous epidermal antioxidants Prevent lipid peroxidationPrevent UV-induced systemic immuni
34、suppresion,維他命 E,抗氧化劑，改善皮膚的細紋，讓皮膚更細緻維他命E和副腎皮質荷爾蒙的分泌有關，能促進真皮層毛細血管的血液流動順暢，增加營養與氧對於皮膚組織的供給維他命E大多來自植物，尤其是蔬菜油，最多者是向日葵花油、麥胚芽、大豆、芝麻油、鰻魚等通常正常成人每天約需要一百四十到兩百一十單位,Cosmetics contain tocopheryl acetate or other tocopheryl estersNo direct antioxidant propertiesNot tocopherol precursors owing to the lack of adequa
35、te esterase in the skin,Antioxidants: Oral supplements,Combination of l-proline, l-lysine, manganese, copper, zinc, quercetin, grape seed extract, N-acetyl d-glucosamine, and glucosamine sulfate was shown to improve wrinkles by 34% Combination of vitamin E, vitamin C, carotenoid, selenium, and proan
36、thocyanidin led to a significant decrease in induction of MMP after UV exposure,輔酵素Q10 (CoQ10),輔脢Q10 (Coenzyme Q10)為一種極易氧化的脂溶性抗氧化劑，可以停止自由基的發生，此種酵素位於粒線體(mitochondria)內，它和維他命K有相似的結構肝臟是合成10的主要場所，但隨年老、疾病的發生，人體製造10的能力會降低，我們也能從肉類、魚類，綠色蔬菜等食物中攝取少量10。更有研究顯示輔酵素Q10缺乏是加速老化的原因用於心臟、胃腸或腦神經的保健 抗氧化、消滅自由基，所以對減緩細胞老化、修
37、復受損的膠原纖維，有一定效果；臨床試驗便曾證實，Co10可減少2、3成皺紋，確能預防老化,Biofactors. 1999;9(2-4):371-8.,-Lipoic acid (-硫辛酸),An antioxidant and anti-inflammatory agent that has been previously shown to reduce the production of transcription factors such as NF-B and indirectly affect the gene expression of inflammatory cytokines
38、,-Lipoic acid (-硫辛酸),One of the most visible roles of lipoic acid is as a cofactor in aerobic metabolism, specifically the pyruvate dehydrogenase complex.Since the early 1990s lipoic acid has been used as a dietary supplement, typically at doses in the range of 100200 mg/day. Treatment with 5% -lipo
39、ic acid has led to significant improvements in clinical and objective measurements of photoaging, including laser profilometry,Br J Dermatol 149; 841849, 2003,Estrogens,Oral estrogen use was associated with a statistically significant decrease in the risk for dry skin and wrinklingTopical estrogen t
40、herapy can also lead to significant increases in collagen, firmness, and elasticity, as well as wrinkle depth measured by optical profilometry,Int J Dermatol 35:669-74, 1996.,Growth factors and cytokines,Topical application of a combination of growth factors and cytokines has been evaluated in a pil
41、ot study for its effect on photoaged skinA majority of patients showed clinical improvement in at least one facial area and a significant change in objective measurements by optical profilometryNew collagen formation was observed in biopsy specimens,FROP-3,Fucose-rich oligo- and polysaccharideStimul
42、ation of fibroblast proliferationDownregulation of skin matrix degrading enzymes as matrix metalloproteinases MMP-2 and MMP-9Free radical scavengingIncrease of skin elastin biosynthesisImprovement of collagen fibrillogenesisIncreases glycosamino-glycan biosynthesis in fibroblast cultures,Skin Resear
43、ch and Technology 2005; 11: 4752,FROP-3,In a pilot study examining skin-surface microrelief, the pattern of fine wrinkling found in skin of any age, a cream containing FROP-3 showed a 10- to 15-year decrease in apparent age after 4 weeks of treatment,Emerging Therapies,Antioxidants,Oral soy isoflavo
44、nes (大豆異黃酮) can enhance the activity of endogenous antioxidant enzymes and protect against UV-induced aging 大豆異黃酮主要來自於豆類植物的子葉與胚軸部分，含量約0.20.4%。是大豆生長中所形成的一次代謝產物，其天然存在的大豆異黃酮共有12種，主要有效六種成分及含量分別為：23% Daidzin(D)、64% Genistin(G)、13% Glycitin和極少量的Daidzein(De)、Genistein(Ge)、Glycitein,Antioxidants,Topical gen
45、istein (金雀異黃素) and N-acetyl cysteines (NAC, N-乙醯基-L-半胱氨酸 )prevent c-Jun and collagenase up-regulation after UV exposure in human skin in vivo an inhibitor of tyrosine kinase activity and may inhibit signal transduction induced by UV light,Antioxidants,Gluconolactone (內酯型葡萄糖酸)a polyhydroxy acid capab
46、le of chelating metals and may also function by scavenging free radicals, thereby protecting skin from some of the damaging effects of UV radiation a preventive treatment for solar elastosis,Antioxidants,Green tea polyphenols (GTPs) potent antioxidants Oral administration of GTPs markedly inhibited
47、UV-induced expression of MMP in mouse skin.Even in the absence of UV light, ()-epigallocatechin-3-gallate, a component of green tea, was shown to inhibit the expression of various MMPs,Silmarin,Silymarin水飛薊是一種名為乳薊(Milk Thistle)植物的精華提取物，專用作治療肝臟毛病1968年，乳薊含有三種具有護肝功能的成分： silibinin， silidianin及silicristi
48、n對肝臟細胞形成一層保護膜，阻擋毒性物質，特別是酒精及環境污染物(農藥、重金屬等)入侵損害肝臟。對於一些急性肝中毒的病症，水飛薊能有一定的解毒功效具有強力的抗氧化功能，能保護肝臟細胞免受自由基破壞，效力遠勝於維生素E促進蛋白質的合成蒙娜麗莎舒敏乳霜,Grape seed,Grape seed proanthycyanidin extract (GSPE): are a group of biologically active polyphenolic bioflavonoidsStrong antioxidants (Clin Cancer Res 6:2921-30, 2000) GSPE containing 5000 ppm resveratrol: Potently upregulates oxidant and tumor necrosis factor-alpha inducible VEGF expression in human keratinocytes (Free Radic Biol Med 31:38-42, 2001),
