REVIEW Kor. J. Aesthet. Cosmetol., Vol. 12 No. 4, , August 2014 해조류추출물후코이단의기능성화장품원료로서의유용성고찰 임진경덕성여자대학교화학과 A Review of the Usability of Fucoidan

Size: px

Start display at page:

Download "REVIEW Kor. J. Aesthet. Cosmetol., Vol. 12 No. 4, , August 2014 해조류추출물후코이단의기능성화장품원료로서의유용성고찰 임진경덕성여자대학교화학과 A Review of the Usability of Fucoidan"

효섭 순
5 years ago
Views:

1 REVIEW 해조류추출물후코이단의기능성화장품원료로서의유용성고찰 임진경덕성여자대학교화학과 A Review of the Usability of Fucoidan Extracted from Brown Seaweed as a Functional Ingredient of Cosmetics Jin Kyung Lim Department of Chemistry, Duk-Sung Women s University Abstract Recently, as peoples interests in Well-being grow, their interests in developing natural, functional cosmetic ingredients are also increasing. The research of Brown Seaweeds; an abundant resource around the world, is actively in progress. Fucoidan; which is contained in Brown Seaweeds, is a Polysaccharide containing Sulfates. Fucoidan is found to have similar properties with Heparin; which is also in blood, but has a larger amount of Sulfates in comparison and is therefore proven to be more effective. The research on the effects of Fucoidan for anti-inflammation, anti-tumors, antivirus, etc. is progressively moving forward. While the research regarding the functionality of Fucoidan in pharmaceuticals and foods is complete, the development of cosmetics using these ingredients is still premature. In this thesis, the research that has been done on the effects of Fucoidan towards hydration, whitening and antioxidants has been reviewed. Also, the prospect of Fucoidan as a functional ingredient in cosmetics has been looked into. However, because the large molecular weight of Fucoidan prevents it from being absorbed properly into the body and the technique to remove the distinct scent of the seaweed has yet to be completed, the value of Fucoidan has not been used to its fullest potential. Therefore, aggressive research in these areas is necessary. Keywords: Fucoidan, Brown Seaweeds, Hydration, Whitening, Anti-oxidants 최근, 건강과웰빙에대한관심이깊어지면서해조류유래 기능성소재에대한많은관심이기울여지고있다. 해조류유 래기능성소재는항종양성 (Lee et al., 1992; Cho et al., 1990), 항바이러스성 (Nakashima et al., 1987), 항혈액응고 (Scot et al., 1987) 및면역력증강등의생리기능을갖는것 으로알려져있으며, 이러한해조류의특이성에착안하여새로 운생리활성물질들이탐색되고있다. 특히, 해조류중, 갈조류 에는 Alginic acid, Fucoidan, laminarin 등과같은생리활성 Corresponding author: Jin Kyong Lim, Department of Chemistry, Duk-Sung Women s University, 419, Ssangmun-Dong, Dobong-Gu, Seoul , Republic of Korea Tel.: , Fax: ginajklim@hotmail.com Received June 9, 2014; Revised August 20, 2014; Accepted August 23, 2014; Published August 30, 2014 이우수한다당이함유되어있다. 이러한다당류는세포내골지체에서합성되어세포조직에존재하며세포보호를위해분비되는데, 갈조류에다량존재하는후코이단은황산기를포함하는다당체로세포내골지체에서합성되어갈조류의세포간조직에주로존재한다. 종에따라엽체의삼출액 (Exudate) 에도존재하는데주로 L-fucose가 α-1,3 결합된골격을가지며 D-xylose, D-galactose 및 Uronic acid 등을함유한함황 hetero형산성다당류로황산기가 C-4 위치에결합되어있으며, 점성이낮고용해성이우수한특징을갖는다 (Mian et al., 1973; Cote et al., 1959). 많은연구를통해다시마의항종양성, 항바이러스, 항돌연변이및면역력증강등의생리적효과가구체적으로확인됨으로써 (Scot et al., 1987; Usui et al., 1980) 다시마의수요는점차증가되고있고, 이와관련하여한국과일본및중국의동아시아에서오랜기간섭취하여온미역과다시마등의갈조류에함유된고분자다당체인후코이단 (Fucoidan) 의여러가지기능성에대한관심이집중되고있다 (Kwon et al., 2006)

2 Figure 2. The structure of Heparin. Figure 1. Fucoidan structure proposed by Percival et al. and Patankar et al. 특히피부에좋은여러가지화장품원료의개발이활발해지 면서, 화장품의보습제로널리사용되고있는히알루론산보다 도높은보습력을갖고있는후코이단의유용성에대한연구및 활용이점차늘어가고있는추세이다. 따라서본논문에서는화장품원료로서의기능성을알아보 기위해후코이단이피부의보습, 미백그리고항산화등에어 떠한효과가있는지살펴보고, 또한문제점등도함께검토하 고자한다. 1. 후코이단의정의 후코이단은 1913 년다시마를연구하던스웨덴웁살라대학 교의 D. Klein 교수가처음으로발견하였다. Klein 교수는다 시마에서분비되는물질을연구하던중에황산기가함유된다 당류를발견하고, 이를후코이딘 (Fucoidin) 으로명명하였는데, 이후국제적인명명기준에의해후코이딘은그명칭이후코이 단 (Fucoidan) 으로변경되었다 (Choi et al., 2000). 후코이단이생체조직을촉촉하게보습하고, 상처를감싸아 물게하며, 염증을예방하는성분으로알려지면서이러한갈조 류에함유된고분자다당체인후코이단의여러가지기능성에 대한관심이집중되고있다. 실제로후코이단이관심을받게된 것은 1990 년대부터인데, 일본인들의장수와낮은암발병률의 근원을연구하던학자들은, 등푸른생선등과함께일본인이 많이먹는다시마와미역에주목하게된다. 건강식품으로서미 역과다시마가갖는성분을연구하던중그핵심성분인후코이 단이주목을받게되면서이에대한연구와이용에대한관심이 본격적으로이루어지기시작했다 (Park et al., 2010). 2. 후코이단의구조후코이단은헤파린 (Heparin) 과유사한구조 (Figure 1, 2) 를가지고있어서헤파린을대체할수있는물질로많이알려지면서많은연구들이진행되고있다 (Dobashi et al., 1989; Pereira et al., 1999). 헤파린은혈액응고를방지하는가장대표적인약제로, 혈액내에서안티트롬빈 (Antithrombin) 이란물질과결합하여트롬빈 (Thrombin) 의작용을억제하는작용을한다. 트롬빈은섬유소원 (Fibrinogen) 을섬유소 (Fibrin) 로전환시켜혈액을응고시키는마지막단계의역할을하기때문에결과적으로트롬빈작용의억제는항응고작용을나타내게된다. 헤파린은그강력한항응고작용으로인해임상에서혈전색전증 (Thromboembolism) 의치료및예방에널리쓰이고있다. 또혈액이우리몸밖에서혈관이외의인공표면과필연적으로접촉할수밖에없는인공심폐기를이용한심장수술에서혈액이응고되는것을막아주는결정적인역할을하고있다. 인체혈액내에존재하는트롬빈 (Thrombin) 의활성저지인자인안티트롬빈 (Antithrombin Ⅲ, AT-Ⅲ) 과헤파린보조인자 (Heparin co-factor Ⅱ, HC Ⅱ) 는분자량이각각 62,000, 65,000인당단백인데, 헤파린과후코이단은서로비슷한아미노산조성을가지고있으나저해작용의범위에차이가난다 (Koo et al., 2001). Church et al. (1989) 의연구에따르면후코이단의트롬빈 (Thrombin) 억제작용은안티트롬빈 (Antithrombin Ⅲ, AT-III) 이아닌, 주로헤파린보조인자 (Heparin cofactor II, HC Ⅱ) 를통해일어난다고보고되었다. 또한후코이단의항혈액응고활성은갈조류의종류, 화학적조성및분자량에따라매우큰차이를보이는데, 황산기의함량이활성에도영향을미치는것으로알려져있다. 후코이단의항혈액응고특성을비교한연구에따르면황산기의몰 (mole) 비가증가할수록항혈액응고작용이증가하는것으로보고되었고생리활성도가높아진다고알려져있다 (Nishino et al., 1991; Koo et al., 1997). Koyanagi et al. (2003) 은황산기의함량을증가시킨후코이단이암세포의증식을효과적으로억제한다고보고하 448

3 후코이단의기능성화장품원료로서의유용성 였다 (Koyanagi et al., 2003). 또한후코이단의항암활성, 항 HIV, 항혈액응고작용등은고분자보다저분자상태인경우에더높은활성이나타난다고보고되고있다. 특히기능성화장품을위해서는피부흡수가가장중요한과제이므로흡수율을높이기위해서, 그리고후코이단의산업적응용성을향상시키기위해서는이것의저분자화하는연구가요구된다 (Bae et al., 2008). 3. 후코이단의기능성화장품원료로서의사용가능성 1) 피부보습제로서의가능성분자의성분중에황산기가붙어있는분자는친수성이강한데, 이러한황산기를다량함유하고있는후코이단은보습력이매우높다. Cha et al. (2010) 등은실험을통하여후코이단이화장품의보습제로가장흔하게쓰여지고있는히알루론산보다더높은보습력을나타내고, 분자량이감소하면보습력이더욱증가함을증명하였다. 그리고후코이단은 IgE (Immunoglobulin E) 혈중농도를감소시키는효과가있다는사실도보고되었는데, 아토피성피부염등으로나타나는알레르기질환의발생원인인 IgE의생성을억제하여, 알러지매개물질의분비를억제함으로써알레르기증상을완화시키고예방하는데후코이단이유용한물질로알려져있다 (Oomizu, 2006). 이러한높은보습력을이용하여아토피성피부염등에적합한기능성화장품의제조가가능하다. 그러나후코이단을추출한해조류에따라황산기의함량차가크므로 (Maruyama et al., 2007; Li et al., 2006; Tatiana et al., 2000; Jun et al., 2005) 적합한종류를선택하여추출하는것도중요한일이라볼수있다. 2) 피부미백제로서의사용가능성멜라닌세포에서티로신 (Tyrosine) 은티로시나아제 (Tyrosinase) 의작용을받아도파 (DOPA, Dihydroxyphenylalanine), 도파퀴논 (DOPA quinone) 으로전화되고, 티로시나아제관련단백질인 TRP-2 (Tyrosinase related protein-2) 와 TRP-1 (Tyrosinase related protein-1) 의작용에의해피부의주된색소인멜라닌으로합성된다. 색소는멜라닌소체형태로피부각질층으로이동, 침착되어흑화를야기한다. 이렇듯과색소침착을유발하는기전을규명하여멜라닌생성을억제하는물질을개발하면미백화장품의유용한원료가될수있을것이다. 기존의멜라닌생성을억제하는물질로서는아스코르비산 (Ascorbic acid), 코직산 (Kojic acid), 알부틴 (Arbutin), 하이드로퀴논 (Hydroquinone) 등이사용되었으나강한미백효과에도불구하고제품안정성이낮다는문제가제기되고있으므로더안정적이고피부친화력이높은천연물질에대한수요자의욕구가증대하고있어천연물질을이용한미 백화장품원료개발의중요성이커지고있다 ( 김은철등, 2005). 해조류에서추출한수용성다당류는식물성다당류로서항염, 항바이러스, 항암치료제등의의약품으로다양하게이용되어왔으며, 최근에는항노화, 보습제등의화장품원료로도응용되어이용되어왔는데 ( 박희연등, 2006; Cumashi et al., 2007; Angstwurm et al., 1995; Moon et al., 2009; Moon et al., 2009; Moon et al., 2008), 이중, 후코이단은멜라닌세포인 B16F10 멜라노마 (melanoma) 세포에서티로시나아제의일종인도파옥시다아제 (DOPA oxidase) 의발현을억제하여멜라닌의합성을막고, 멜라닌세포의가지돌기의형성을억제하여멜라닌소체가각질세포로이동하는것을막음으로써피부의멜라닌색소침착을방지하는역할을하는것으로보고되었다 (Jung et al., 2008). 3) 항산화물질로서의사용가능성해조류로부터의추출물이, 면역증강, 항종양성, 그리고항산화역할등을포함한약리활동에뛰어난효과를보이므로특별한관심을끌어오고있다 (Kang et al., 2005). UV는진피조직내에쉽게침투하며피부노화에지속적으로관여한다. 따라서진피섬유아세포는 UV에의해생기는광피부노화의항산화효과를조사하는유용한모델로사용된다 (Offord et al., 2002). UVB는성장, 분화, 복제로인한노쇠, 그리고결합조직의손상과관련된활성산소의생성, DNA손상, 그리고세포질의신호변환체계의활성화의결과로세포의발색단과감광성물질에작용한다 (Helenius et al., 1999). 많은연구자들에따르면, UVB는세포내의 GSH (Glutathione), 세포막의 Vit. E, 그리고세포막의유동성등의극적인감소를유도하며, 더욱이 MDA (Malondialdehyde) 수치를증가시킨다고한다 (Carini et al., 2000; O Connor et al., 1998). GSH는세포내의가장기본적인항산화물질이기때문에, GSH의감소는 UVB가조사된세포내의활성산소가축적됨으로써세포의고사에깊이관여한다고볼수있다 (Lee et al., 2004). 이러한 UV에의한피부손상을막기위해, 후코이단을이용한 GSH, MDA, ROS (Reactive oxygen species) 등의수치를조사하는여러가지실험들이실행되었고그에따른결과를살펴보면, 후코이단을처치한섬유아세포는처치하지않은세포에비해뛰어난개선효과를보여주고있음을알수있었다. 대표적인항산화제인비타민 C는수용액에서쉽게산화되어분해되기때문에의약품, 화장품, 식품등에이용할때장기보관이어렵고, 색상, 변색등많은문제가있어피부외용제로서비타민C 자체를사용하는경우는거의없는데, 후코이단은수용액상에서안정하기때문에화장품에원료로사용하면항산화제의역할도할수있음을보인것이다. 그러나후코이단은분자량이약 200,000 Da 이상의고분자여서그자체로는체내흡수율이 449

4 현저히낮지만저분자화되면체내흡수율이현저히증가하고 또한약리적인효과를증대시킬수있음이실험으로밝혀졌다 (Alain et al., 1996). 4. 후코이단의피부흡수를위한저분자화 후코이단은분자량이매우큰다당류로서피부에직접적 으로흡수되기가매우어렵기때문에, 기능성화장품원료로 서의응용을위해서는저분자화하는것이가장시급한문제 로대두되고있다. 후코이단의저분자화방법은, 산분해, 라디 칼분해 (Lionel et al., 1999), 효소에의한분해 (Regis et al., 1999), 그리고접촉글로우방전전기분해방법 (Contact Glow Discharge Electrolysis, CGDE) (Dodgson et al., 1961) 등이 있는데, 이중, 안전한방법으로는접촉글로우방전전기분해방 법이유용하게사용되고있다. CGDE 는높은전압에서이루어 지는데, 이과정에서양극과접한전해질이분해되면서반응성 이강한라디칼등을형성해일정의플라즈마상태가된다. 양 극근처의플라즈마반응영역에서, 다음반응 (Susanta et al., 1998) 으로생성된라디칼에의해고분자가저분자로분해될수 있음을알아냈다. H 2 O H + OH H + H H 2 OH + OH H 2 O + O 2 H + OH H 2 O 이렇게저분자화된후코이단을이용한여러가지임상실험이 진행되고있고, 보습, 미백그리고항산화등에서효과가입증 되었다. 해조류는항종양성, 항바이러스성, 항혈액응고및면역력증 강등의생리기능을갖는것으로알려져있다. 특히, 갈조류에 는알긴산 (Alginic acid), 후코이단, 라미나린 (Laminarin) 등 과같은생리활성이우수한다당이함유되어있다. 본논문에 서는이중, 후코이단의보습효과, 미백그리고항산화효과 에대해알아보았다. 후코이단의뛰어난보습력은분자구조내 의황산기에의해나타나는데, Cha et al. (2010) 의실험을통 해히알루론산보다더높은보습력이있음이증명되었다. 또한 OOmizu (2006) 은실험을통해 IgE 혈중농도를저하시킴을밝 혀알러지에도효과가있음을알아냈다. 후코이단의미백효과 를알아보는실험에서, Jung et al. (2008) 은, 후코이단이멜라 닌세포인 B16F10 멜라노마세포에서티로시나아제의일종인 도파옥시다아제의발현을억제하여멜라닌의합성을막고, 멜라닌세포의가지돌기의형성을억제하여멜라닌소체가각질세포로이동하는것을막음으로써피부의멜라닌색소침착을방지하는역할을하는것을밝혀냈다. 항산화효능실험에서도, UV에의한피부손상을알아본결과, 후코이단을처치한피부섬유아세포의항산화반응이뛰어남이증명되었다. 이렇듯, 기능성화장품원료로서의가능성은여러학자들에의해증명되었으나아직도해결해야할문제들이여럿있음을알수있었다. 첫째, 후코이단은분자량이매우큰다당류로서피부침투가용이하지않으므로이것의저분자화가요구되고있으며현재많은연구가진행되고있다. 두번째로, 해조류특유의비릿한냄새로인해화장품을제조함에있어서어려움이있으므로무엇보다도비린냄새의제거가요구되고있고이러한연구또한진행되고있음을알수있었다. 이러한몇가지문제점을해결할수있다면, 저비용, 고효율의기능성원료로서후코이단의유용성은더욱높아질것으로사료된다. 김은철, 안소영, 홍은숙, 이광화, 김은기, 노경호. 천연물에포함된미백성분의추출및미백효과. 한국공업화학회지, 16: , 박희연, 임치원, 김연계, 윤호동, 이가정. 매생이열수추출물의면역및항암활성. 한국응용생명화학회지, 49: , Angstwurm K, Weber JR, Segert A, Bürger W, Weih M, Freyer D, Einhäupl KM, Dirnagl U. Fucoidin, a polysaccharide inhibiting leukocyte rolling, attenuates inflammatory responses in experimental pneumococcal meningitis in rats. Neurosci. Lett., 191: 1-4, Alain N, Frederic C, Catherine BV, Patrick D. Jacqueline J. Anticoagulant low molecular weight fucans produced by radical process and ion exchange chromatography of high molecular weight fucans extracted from the brown seaweed Ascophyllum Nodusum. Carbohydr. Res., 289: , Bae JS, Lee JS, Kim YS, Soi WJ, Lee H, Chun JY, Park KP. Depolymerization of fucoidan by contact glow discharge electrolysis (CGDE). Kor. Chem. Eng. Res., 46: , Cha SH, Lee JS, Kim YS, Kim DU, Moon JC. Park KP. Properties of Fucoidan as raw materials of water

5 후코이단의기능성화장품원료로서의유용성 holding cream cosmetics. Kor. Chem. Eng. Res., 48: 27-32, Cho, KJ, Lee, YS, Ryu, BH. Antitumor effect and Immunology activity of seaweeds toward sarcoma-180. Bull. Kor. Fish. Soc., 23: , Cote RH. Disaccharides from Fucoidan. J. Chem. Soc., 10: , Choi J, Kim D, Park S, Kim D, Kim C, Koo J. Effects sea tangle (Laminaria Japonica) extract and Fucoidan components on lipid metabolism of stressed mouse. J. Kor. Fish. Soc., 33: , Church FC, Meade JB, Treanor RE, Winna HC. Antithrombin activity of Fucoidan. J. Biol. Chem., 264: , Cumashi A, Ushakova NA, Preobrazhenskaya ME, D Incecco A, Piccoli A, Totani L, Tinari N, Morozevich GE, Berman AE, Bilan MI, et al. A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds. Glycobiology, 17: , Carini M, Aldini G, Bombardelli E, Morazzoni P, Maffei Facino, R. UVB-induced hemolysis of rat erythrocytes: protective effect of procyanidins from grape seeds. Life Sci., 67: , Dodgson, KS. Determination of Inorganic Sulphate in Studies on the Enzymic and Non-enzymic Hydrolysis of Carbohydrate and Other Sulphate Esters. Biochem. J., 78: 312, Dobashi, K, Nishino, T, Fufihara, M, Nagumo, T. Isolation and preliminary characterization of fucose containing sulfated polysaccharide with blood anticoagulant activity from the brown seaweed. Carbohydr. Res., 194: , Helenius M, Makelainen L, Salminen A. Attenuation of NF-kappa B signaling response to UVB light during cellular senescence. Exp. Cell Res., 248: , Jung SH. Effect of Fucoidan Extracted from Seaweed as a Skin Whitener. Graduate School, Kosin University, Ph.D thesis, Jun S, Urara WF, Hroshi M, Yoshiharu M, Mitsuaki K, Masahiro W. Proportion of Murine Cytotoxic T Cells is increased by high molecular-weight Fucoidan extracted from Okinawa Mozuku (Cladosiphon okamuranus). J. Health Sci., 51: , Kwon DJ, Lim ST, Chung YJ, Park SH, Kweon DK. Comprehension and practical use of Fucoidan extracted from brown seaweeds. Food Sci. Ind., 39: 73-80, Koo JG. Structural characterization of purified fucoidan from Laminaria religiosa, sporophylls of Undaria pinnatifida, Hizikia fusiforme and Sargassum fulvellum in Korea. Kor. J. Fish. Soc., 30: , Koyanagi S, Tanigawa N, Nakagawa H, Soeda S, Shimeno H. Oversulfation for Fucoidan enhances its antiangiogenic and antitumor activities. Biochem. Pharmacol., 65: , Koo JG, Chol YS, Kwak JK. Blood anticoagulant activity of fucoidan from Sporophylls of Undaria pinnatifida, Laminaria religiosa, Hizikia fusiforme and Sargassum fulvellum in Korea. J. Kor. Fish. Soc., 34: , Kang KA, Bu HD, Park DS, Go GM, Jee Y, Shin T, Hyun JW. Anti-oxidant activity of ethanol extract of Callophyllis Japonica. Phytother. Res., 19: , Lee YS, Kim DS, Ryu BH, Lee SH. Antitumor and immunomodulating effects of seaweeds toward sarcoma-180 cell. J. Kor. Soc. Food Nutr., 21: , Li B, Wei XJ, Sun JL, Xu SY. Structural Investigation of a Fucoidan containing a fucose-free core from the Brown Seaweed. Carbohydr. Res., 341: , Lee CS, Park SY, Ko HH, Han ES. Effect of change in cellular GSH levels on mitochondrial damage and cell viability loss due to mitomycin c in small cell lung cancer cells. Biochem. Pharmacol., 68: , Lionel C, Alain F, Frederic C, Nelly K, Corinne S, Anne- Marie F, Catherine B. Further data on the structure of Brown Seaweed Fucans: Relationships with anticoagulant activity. Carbohydr. Res., 319: , Mian AJ, Percival E. Carbohydrates of the brown 451

6 seaweeds Himanthalia lorea, Bifucaria bifurcate and Padina pavonia part Ⅱ. structural studies of the fucan. Carbohydr. Res., 26: , Maruyama H, Tanaka M, Matsuhisa M, Hashimoto M. Sasahara, T. The suppressive effect of Mekabu Fucoidan on an attachment of Cryptosporidium Parvum Oocysts to the intestinal epithelial cells in Neonatal Mice. Life Sci., 80: , Moon HJ, Lee SH, Ku MJ, Yu BC, Jeon MJ, Jeong SH, Stonik VA, Zvyagintseva TN, Ermakova SP, Lee YH. Fucoidan inhibits UVB-induced MMP-1 promoter expression and down regulation of type I procollagen synthesis in human skin fibroblasts. Eur. J. Dermatol., 19: , Moon HJ, Park KS, Ku MJ, Lee MS, Jeong SH, Imbs TI, Zvyagintseva TN, Ermakova SP, Lee YH: Effect of Costaria Costata Fucoidan on expression of matrix metalloproteinase-1 promoter, mrna, and protein. J. Nat. Prod., 72: , Moon HJ, Lee SR, Shim SN, Jeong SH, Stonik VA, Rasskazov VA, Zvyagintseva T, Lee YH: Fucoidan inhibits UVB-induced MMP-1 expression in human skin fibroblasts. Biol. Pharm. Bull., 31: , Nakashima H, Kido, Y, Kobayashi, N, Motoki, Y, Neushal, M, Yamamoto, N. Purification and characterization of an avian myeloblastosis and human immunodeficiency virus reverse transcriptase inhibitor sulfated polysaccharide extracted from sea algae. Agents. Chemother., 31: , Nishino T, Aizu Y, Nagumo, T. The relationship between the molecular weight and the anticoagulant activity of two types of fucan sulftes from the brown seaweed Ecklonia kurome. Agri. Biol. Chem., 55: , Oomizu S. Fucoidan Prevents Cegermline Transcription and NFKE p52 Trans Location for IgE Production in B Cells. Biochem. Biophy. Res. Comm., 350: 501, O Connor I, O Brien N. Modulation of UVA light-induced oxidative stress by beta-carotene, lutein and astaxanthin in cultured fibroblasts. J. Dermatol. Sci., 16: , Offord EA, Gautier JC, Avanti O, Scaletta C, Runge F, Kramer K, Applegate LA. Photoprotective potential of Lycopene, beta-carotene, vitamin E, vitamin C and Carnosic acid in UVA-irradiated human skin fibroblasts. Free Radic. Biol. Med., 32: , Pereira MS, Mulloy B, Mourao PAS. Structure and anticoagulant activity of sulfated fucans. J. Biol. Chem., 274: , Regis D, Oliver B, Jacqueline J, Nicole G. Degradation of Algal(Ascophyllum Nodusom) Fucoidan by an Enzymatic Activity Contained in Digestive glands if the Marine Molluse Pecten Maximus, Carbohydr. Res., 322: , Scot M, Colin GM, David J, Mills L, Brian JB. Estimation of meiobenthic nematode diversity by non specialists. Marine Pollu. Bulletin., 18: , Susanta KS, Rajeshwar S, Ashok KS. A Study on the Origin of Non-faradaic behavior of Anodic Contact Glow Discharge Electrolysis, J. Electrochem. Soc., 145: , Tatiana NZ, Natalia MS, Irina VN, Andrey SS, Pavel AL, Ludmila AE. Inhibition of complement activation by water-soluble Polysaccharides of some Far-Eastern Brown Seaweeds. Comparative Biochem. Physiol. Part C, 126: , Usui T, Asari K, Mizuno T. Isolation of highly fucoidan from Eisenia bicyclis and its antitumor activity. Agric. Biol. Chem., 44: ,

386-390.hwp

386-390.hwp 386 HANYANG MEDICAL REVIEWS Vol. 29 No. 4, 2009 우리나라 미숙아의 통계와 의료비용 Statistics and Medical Cost of Preterm in Korea 윤혜선 을지대학교 노원을지병원 소아청소년과학교실 Hye Sun Yoon, M.D., Ph.D., Department of Pediatrics, Nowon