기능성화장품의종류및법규 중부대학교화장품과학과송기세
피부의색 1. Melanin 색소의양과분포 : 피부색깔결정의주요인자 2. 헤모글로빈 (Hemoglobin in the blood vessel) : 백색의피부 melanin 이적고표피층의투명도가높아혈액속의헤모글로빈의영향을강하게나타나분홍색으로느껴짐 : 흑색의피부 검은색의멜라닌양이많아서상대적으로혈액의영향이적음 3. 카로티노이드 (carotenes in the hypodermal fat) 같은색소의양 4. 피부의두께와반사도및혈류량 5. 신체부위별, 계절별, 건강상태나스트레스등에의해변화
멜라닌형성세포 (Melanocytes) 멜라노사이트
Melanin synthesis
Melanogenesis Tyrosine Tyrosinase hydroxylation Dihydoxy-phenylalanine(DOPA) Rate limiting stage oxidation Tyrosinase DOPA quinone -SH Eumelanin( 흑갈색 ) Pheomelanin ( 적황색 )
Melanogenesis 1. Melanin : 피부색깔결정의주요인자 2. Tyrosinase : Active site 에 copper 가함유된 metaloenzyme : melanin 합성에서제일중요한역할 3. 미백원료 : tyrosinase activity 를억제 : 세포수준에서 melanogenesis 억제 (melanin assay) : Human 에서적용하기힘든경우가대부분 적절한효과 Safety Stability 생산비, marketing 비사용자의 perception ( 감성 )
Melanogenesis 1. In Vitro 1) Tyrosinase activity 2) B16 melanoma cells 2. In Vivo 1) Brownish guinea pigs -2주간 UV light 조사 -6주간 EA, Hydroquinone, Kojic acid, Arbutin(1%) 처리 2) 임상실험 - UV 조사전 6주간샘플바름 - 조사후 6주간샘플바름
참고 ) 미백원료의가능한효능평가단계
(H. Shimogaki et al. Int. J. Cos. Sci. 22 : 291-303. 2000)
EA 1%
동물피부를잘라멜라닌을볼수있게염색한실험 (UV 조사후샘플처리한것 ) 검은색부분이멜라닌임
Results(In Vivo, 인체실험 )
미백기능성화장품의정의 ( 한국 ) 화장품법제 2 조에규정 피부의미백에도움을주는제품 피부에멜라닌색소가침착하는것을방지하여기미, 주근깨등의생성을억제함으로써피부의미백에도움을주는기능을가진화장품 피부에침착된멜라닌색소의색을엷게하여피부의미백에도움을주는기능을가진화장품
기능성화장품의지정고시 ( 식약청고시제 2005-4 호 ) 피부의미백에도움을주는제품의성분및함량 - 닥나무추출물 2.0% - 알부틴 2.0% - 에칠아스코빌에텔 2.0% - 유용성감초추출물 0.05% - 아스코빌글로코사이드 2% - 마그네슘아스코빌포스페이트 3%
1) 멜라닌합성효소인 Tyrosinase 활성억제저해물질 1 보결분자인구리와의 chelating에의한비경쟁적저해작용 Ex) Kojic acid 2 Tyrosinase 기질유사물질로경쟁적으로저해작용 Ex) Arbutin 2) 활성산소소거법및지질과산화억제 ( 환원 ) 3) 각질세포를벗겨내어멜라닌색소를제거하는물질 Ex) AHA, BHA 4) 멜라닌세포 (Melanocytes) 자체를사멸시키는물질 Ex) Hydroquinone
미백에도움을주는기능성화장품 총 8 품목 ( 제제 3 품목, 원료 5 품목 ) 1 알부틴로션 2 알부틴액 3 알부틴크림 4 닥나무추출물 5 아스코빌글로코사이드 6 알부틴 7 에칠아스코빌에텔 8 유용성감초추출물
The action mechanism of the depigmentation materials 원료기작기타 Sunscreen agents UV 차단 UV 차단이외에는 색소침착에는효과 없음 SOD Glutathione Glucosamine Galactosamine Free radical 제거 Tyrosinase 활성억제 확실한효과이나불안정함. Tyrosinase 에특이적이지않음. 독성가능성 Arbutin Tyrosinase 활성억제확실한효과 Kojic acid 멜라닌생합성에서중간매개물질방해 약간의피부자극알러지, 불안정
The action mechanism of the depigmentation materials 원료기작기타 Hydroquinone Tocopherol Vitamin C der. Azelaic acid AHA Vitamin A Licorice extract 멜라노사이트의독성효과 멜라닌합성감소 Keratinocyte 를통한멜라닌제거를촉진 피부재생을증진피부 exfoliate Tyrosinase 저해 Free radical 제거 피부에높은독성 확실한효과이나불안정함. 확실한효과 확실한효과 피부자극
최근연구되는기전 1) Protein Kinase C : Protein Kinase C의 β form isomer(pkc- β) tyrosinase 활성촉진 Melanogenesis : PKC- β Inhibition tyrosinase 활성억제 Melanogenesis 억제 : 피부장벽회복에도효과가있음 2) Melanosome Transfer : Melanosome 이 melanocyte에서 keratinocytes 로 transfer(phagocytosis) 피부의 pigmentation : PAR-2(Protease-activated receptor-2) keratinocytes에서만발현됨 PAR-2 activation melanosome의 phagocytosis Melanogenesis 3) MITF(Microphthalmia-associated transcription factor) : MITF가 Tyrosinase의 M-box에결합 Pigmentation 증가 : DHLA(dihydrolipoic acid) MITF 의발현감소시킴 Skin lightening
Tyrosinase Activation by PKC-ß
Melanosome transfer (Raymond E. Boissy. Exp. Dermatol 12(3) : 5-12. 2003)
* The keratinocytes PAR-2 is involved in melanosome uptake. (Pigment cell res 17:241-251, 2004)
MlTF(Microphthalmia-associated transcription factor) Pigment Cell Res. 13 : 230-240 (2000)
2) the uptake and distribution of melanosome in recipient keratinocytes 3) melanin and melanosome degradation and turnover of pigmented keratinocytes 1)transcription and activity of tyrosinase, tyrosinase-related protein- 1.2 (TRP-1,2), and/or peroxidase Tyr : Tyrosinase, M : Melanosome, ROS : Reactive Oxygen Species
Before melanin synthesis During melanin synthesis After melanin synthesis Tyrosinase transciption C2-ceramide Tretinoin Tyrosinase glycosylation Tyrosinase inhibition Calcium D-pantetheine- S-sulphonate Hydroquinone 4-hydroxy-anisole 4-S-CAP & derivatives Arbutin Aloesin Azelaic acid Kojic acid Methyl gentisate Ellagic acid Resv eratrol Oxyreveratrol Peroxidase inhibition Methimazole Phenols/catechols Product reduction and ROS scavengers Ascorbic acid Ascorbic acid Palmitate VC-PMG Thioctic acid alpha-toc D.L-alpha TF Hy drocumarins Tyrosinase degradation Linoleic acid alpha-linolenic acid Inhibition of melanosome transfer Skin turnover acceleration Serine protease inhibitors Lecthine and neoglycoproteins Soybean/milk extracts Lactic acid Glycolic acid Liquiritin Niacinamide RW-50353 Retinoic acid Linoleic acid
참고 ) 국내외장업사의미백원료 회사명 LVMH L Oreal Shiseido Kanebo Kao Kose Estee Lauder Pacific LG 미백원료 Vitamin C der., SNOW, Hypotaurine Kojic acid, Liquiritin Arbutin, Ascorbyl glucoside Vitamin C der. 미네랄, 효소 (MT) Chamomile ET Bio Kojic acid, Vitamin C der. Bio SOD Biowhite, Tourmaline Co Q10, Kojic acid, Vitagen, 닥나무추출물 Arbutin, Phytoclear EL-1, 반하
Reference The Expression and activation of protease-activated receptor-2 correlate with skin color. Laura Babiarz-Magee et al, Pigment cell res 17:241-251, 2004. The Effect of Niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. T. Hakozaki et al. Br J Dermatol 147:20-31,2002. Inhibition of melanosome transfer results in skin lightening. Miri Seiberg et al. J Invest Dermatol 115:162-167, 2000. Melanosome transfer to and translocation in the keratinocytes. Raymond E. Boissy. Exp Dermatol 12(2):5-12, 2003.
Reference MITF : A Stream flowing for pigment cells. Masayoshi Tachibana. Pigment Cell Res. 13 : 230-240 (2000) In vitro and in vivo evaluation of ellagic acid on melanogenesis inhibition. H. Shimogaki. et al. Int. J. Cos. Sci. 22 : 291-303. 2000. Park et al. J Bio. Chem. 271 : 164870 16478. 1999. SID (The Society for Investigative Dermatology) - 63rd Annual Meeting 2002, 65th Annual Meeting 2004 식품의약안전청 (KFDA) 주최세미나 - 기능성화장품연구동향 (2003.11.7) - 기능성화장품심사설명회 (2005.3.10)