Officia! Journal of International Society of Cosmetic Dermatology INTERNATIONAL EDIEMME Volume 9 - Number I January/March 1991 ISSN 0392-8543 Sped. abb. post. JV 0 70 Per Campioni Medici e Documentazione Scientifica: Mavi Sud s.r.l. - Viale dell'Industria, 1 - 04011 Aprilia (LT) Tel. (06) 9281235 /6/7 - Fax (06) 9281523 • • -. El,IUUllOHE IORATANff ........ ......._~ 200rn1e 50m1C lW lW 'I. ~ - ~ Ln7. l11éM La ricerca scientifica nella dermocosmesi Mavi Sud Sri - Viale dell'Industria, 1 - 04011 Aprilia <LT> PCL-liquid and PCL-solid were launched 25 years ago. Since then, they have found their way into well over 10 billion units of cosmetics, the world over. Their use is still spreading. There are no finer emollients. PCL-liquid und PCL-solid are non-greasy, non-occlusive, water-resistant wax esters. They spread readily on the skin surface. DRAGOCO DERMATOLOGIA COSMETOLOGICA A cura di P. Morganti e L. Muscardin Ed. Inter na tional Ediemme S e zione IX Annessi cutanei e dermocosmesi 30 Ghiandole sudoripare e sebacee 31 Deodoranti e antisudore 32 Stru ttura e proprietà dei capelli 33 Detersione, protezione e normalizzazione dei capelli e del cuoio Indice 1° Volume capelluto S ezione I Considerazioni Generali 1 Cenni storici 2 La bellezza della figura umana Sezione II Fisiologia e Biologia della cute 3 Sviluppo della pelle 4 La struttura della cute 5 Biochimica e Fisiologia dell'epidermide 6 Biologia del tessuto connettivo 7 Sistema Vascolare ed innervazione della cute S ezion e III La Cute come organo di assor bimento 8 Nozioni basilari sulla permeabilità e sull'assorbimento 9 Membrane e assorbimento 10 Metabolismo della cute e degli annessi cutanei 34 Cosmetici decorativi ad effetto duraturo 35 Le unghie 36 P rodotti decorativi ad effetto temporaneo superficiale Indice 3° Volume Sezione X Seborrea e dermocosm esi 37 Caratteristiche chimico-fisiche e funzioni fisiologiche del sebo 38 Produzione e modificazioni del sebo nel sano e nel seborroico 39 Influenza dei trattamenti cosmetologici sui lipidi di superfice del viso e del capillizio 40 Attività ormonale e ghiandole sebacee 41 Il problema terapeutico dell'acne 42 Possibilità terapeutiche nella seborrea Sezione Xl M~lanogenesi e dermocosmesi Sezio n e IV Chimica e Chimico-Fisica dei preparati topici 11 Materie prime e principi attivi di uso cosmetologico 43 Il sistema pigmentario 44 Filtri solari, pigmentanti diretti e depigmenta nti 12 Emulsioni ed emulsionanti 13 Tensioattivi di uso cosmetico 14 Gli antiossidanti e i fenomeni ossidativi dei grassi 15 Antimicrobici e preservanti cutanei 16 La profumazione dei cosmetici 17 Chimica e tossicologia dei coloran ti 18 Prodotti cosmetici in aerosol Indice 2° Volume Sezione XII Mu cose orali e dermocosmesi 45 La salute della bocca e dei denti 46 Profilassi ed igiene dei denti e della bocca 47 Preparazioni cosmetiche per la cavità orale S ezione XIII Prodot ti speciali 48 Omeopatia e cosmetici 49 SolUZioni per lenti a contatto 50 Cosmetici ipoallergcnici 51 Cosmesi su basi naturali S e zio n e V Trattam enti dermocosmetici del viso e del corpo 19 Detersione, protezione e normalizzarione della peJle 20 La cosmesi per l'uomo 21 Cosmetici per bambini 22 Preparati per il bagno 23 Maschere e peeling 24 I Depilanti Sezio n e VI La cute senile 25 Invecchiamento cutaneo 26 n trattamenl<> della cute senile S ezione VII Cosmetici e Psiche 27 Aspetti psicosomatici e somatopsichici in dermatologia cosmetologica Sezione VIII I danni cutanei 28 Patologia cutanea da cosmetici su base immunologica 29 Danni da cosmetici S e-. done XIV Tratta me nti estetici correttivi 52 Interventi correttivi di chirurgia plastica 53 Laserterapia 54 Crioterapia 55 Principi di mesoterapia 56 Ionoforesi 57 Interventi correttivi di "camouffiage" Sezione XV Controlli d ermotossicologici 58 Valutazione delle materie prime e dei cosmetici finiti 59 Controlli tossicologici delle materie prime e del prodot to finito 60 Cosmetognosia. Funzionalità ed efficacia dci prodotti cosmetici S e zio n e XVI Problemi normativi e di M a rketing 61 Nozioni cli ma rketing e di pubblicità 62 Grafica pubblicitaria: implicazioni ps icologiche 63 Normative di legge s ui cosmetici nei vari paesi de l mondo 64 La responsabilità civile dei trattame nti cosmetici 65 Giuctizio mectico-lega le del da nno estetico INFORMAZIONI PER L'AC QUISTO Il pagamento di Lit. 120.000 (Centovenlimila) per l'acquisto del 1° volume di Dermatologia Cosmetologica può essere effettuato mediante assegni di conto corrente o per contanti indirizzandoli a: INTERNATIONAL EDIEMME Via Innocen zo XI, 41 - 00165 ROMA cfc bancario n. 2961212 Banco di Santo Spi rito Ag. 23, 00165 ROMA O Pre n o to fin d a ora i vol unri 2° e 3° Con la presente richiedo: Copie n . ........................................ del Volume n. 1 O Invio i n con trassegno O Accludo assegno n . ................................................................................................................................. (a pagamento quale antic:!po di prenotazione ) TIMBRO E FIRMA Specificarecondizionidipagamen toefomireN" Codice F i scal e se è r i chiesta fattu ra. MAVIGEN A f~ll.,frll:t"H~'lt(H rtt!~,: \' Ql ttt7. mav1 Lm mav1 La ricerca scientifica nella dermocosmesl. Per Campioni Medici e Documentazione Scientifica scrivere a : Mavl Sud Sri · Direzione Propaganda Medica· Viale dell'Industria I · 0401 I Aprilia fLTJ . • EXTRA DELICATO AL COlLAGENE -~!."'~ Lm mav1 La ricerca scientifica nella dermocosmesl. Per Campioni Medici e Documentazione Scientifica scrivere a: Mavl Sud Sri - Direzione Propaganda Medica - Vlale dell'Industria I - 0401 I Aprllla fl TJ. DALLA RICERCA MAVI GLI IDRATANTI A PERMEABILITA' SELETTIVA IDRATAZIONE NORMALE IDRATAZIONE MEDIA IDRATAZIONE FORTE per pelle da normale a grassa per pelle da normale a secca trattamento intensivo per ogni tipo di pelle GEL IDRATANTE a fattore di idratazione 5. Reidratante cutaneo leggero per la pelle da normale a grassa. Arricchito con PCA noto componente dell'NMF, glicina, collagene "attivo" e filtri UVA- UVB. CREMA a fattore di idratazione 10. Idratante cutaneo per pelli da normali a secche. Arricchita con acido gamma-linolenico, PCA, collagene "attivo", speciali umettanti, glicina e filtri UVA - UVB. GEL-EMULSIONE monodose, a fattore di idratazione 20, privo di conservanti. Idratante cutaneo per pelli particolarmente sensibi li e disidratate ad alta concentrazione di principi attivi per tutti i tipi di pel le. Arricchito con acido gamma-l inolenico, fosfolipidi, speciali olii ramificati e filtri UVA- UVB. L'IDRATAZIONE E L'ASSORBIMENTO PROGRAMMATI CON PRECISI INDICI NUMERICI lf.}'7. maV1 La ricerca scientifica nella dermocosmesi. Mavi Sud S.r.l. - Viale dell'Industria, 1 - 0401 1 Aprilia (LT). "'o E a: "' .\! '§ o _,"' > f- CfJ QUICl<~ MOIST 1:1 lfN1 rT1éM La ricerca scientifica nella dermocosmesi Mavi Sud s.r.l. - Viale dell'Industria, 1 - 04011 Aprilia (LT) A new look at old skin: A challenge to cosmetology lnternational Meeting on Cosmetic Dermatology, Rome, ltaly, March 7-9, 1985 1st Editors: P. Morganti, W. Montagna The proceedings contained in this volume provide comprehensive view of the different aspects of the skin aging with its cosmetological implications. Contents (main chapters) Readership: Third year undergraduat es , research workers in the field of Cosmetic Chemistry, Biochemistry, Medicine , Pharmacy and Pharmacology , researchers and managers working in the cosmetic and pharmaceutical industries. A NEW LOOK AT OLD SKIN: A CHALLANGE TO COSMETOLOGY Editors: P. Morganti. W. Montagna The problems of the aged (R. Butler) Nutrition ond aging (M. Proja) Common structural changes in aging human skin (W. Montagna) An ove rview of physiological changes (8.A. Gilchrest) The skin as a barrier and a homeostatic compartment of the body (G. Esposito) Skin collagen cross links natural and unnatural (J.P. Bentley) Aging changes in the mucus membranes (A. Jarrett) Changes in C uta neous appendages (FJ.G. Ebling) Sebum secretion rates in relation to age: A new look (J.S. Strauss) Aging skìn and Sun Damage (F Serri, L. Celleno) Sunlight, age and skin cancer (J. C. van der Leun) Stereology of the skin surface: a comparison between ageing and UV-induced damages (P. Corcuff) Cosmetic w rinkle smoothing (A. Meybeck) Collagen in cosmetic formulations: A contribution to research on aging skin(I. Beyssac) The cosmetic make-over in ederly women (A.M.Kligman) Essential fatty acids and skin aging (P. Morganti, S.O. Randazzo) Treatment cosmetics and aging (L. C. Calvo) Proceeding of 1.st lnternational Meeting on Cosmetic Dermatology. Rome. ltaly. March 7-9. 1985. 1986; 17-24 cm. 400 pages. Hardbound In ltaly L. lCXHXXJ; ISSN 0393-5779 International Society of Cosmetic Dermatology PRESIDENT Coleman Jacobson (USA) HONORARY PRESIDENT William Montagna (USA) VICE-PRESIDENTS Fancis John Ebling (England) Emiliano Panconesi (Jtaly) Rodo lfo Paoletti (Italy) SECRETARY-GENERAL Pierfrancesco Morganti (ltaly) PROGRAM DIRECTOR M. Brodie James (USA) BOARD OF TRUSTEES Pie rre Agache (France) Fritz Ke mpe r (Germany) Lawrence Parish (USA) W.E. Parish (England) Wolfgang Raab (Austria) Salvatore Randazzo (ltaly) Hans Schaefer (France) ADVISORY BOARD William Abramovitz (Venezuela) Mohamed Amer (Egypt) Ruben David Azulay (Brasi!) Claude Be nezra (France) I.A. Bernstein (USA) O . Bine! (France) Otto Braun- Falco (Germagy) Peter Fritzch (Austria) J. Morton Gillespie (Austral ia) Marwall Harahap (Indones ia) Vaino Hopsy-Havu (Finland) Stephanie Jablonska (Poland) A. Jarret (England) Jon Kabara (USA) F'. Kardel Vegas (Venezuela) Ch.M. Lapiere (Belgium) Juhlin Lennart (Swedén) R.S. Lester (Canada) Howard Maibach ( USA) Ronald Marks (Wa les) Jose Mascaro (Spai n) J.P. Ortonne (France) G .E. Pierard (Belgium) Jaime Rubin (Argentina) Wolfgang Rupilius (Germany) Raul Vignale (Uruguay) Jacques Wepierre (France) Chu-Kwan Wong (Taiwan) Trimestrale di Dermatologia Cosmetologica Quarterly Review of Cosmetic Dermatology E DITO R P. MORGANTI Ph D. S ECRETARY GENE RA L INTERNATIONA L SOCIETY of COSMETIC DERM ATOLOGY Vin Innocenzo Xl , 4 1 - 00165 Romn - (lrnly) - Fax 06/63.80.839 ASSOC IAT E E DITOR S.D. RANDAZZO M.D. Profossor of EXPERIMENTAL DERMATOLOGY UN IVERSITY OP CATANIA ASS ISTANT EDITO R M.B. JAMES M.D. PROGRAM DIRECTOR INTERNATIONAL SOCIETY of COSMETIC DERMATOLOGY JAMES C LIN IC 34 1-:orcsidc Commori Fn.lmouth. ~1:lìnc ~ 105 USA - Fax 001-207-7755182 Via lacona. 7 - 95 124 Catanìa (h aly) ED ITO RIAL AD VIS ORY llOARD P. AGACllE G. llELLOMONTE IV.F. llERGFELD ll.llERRA R.CAPUTO O. CARLESIMO D.CER IM ELE E. C lllACClll E RI N I J.COHE M.A. DINA F.J.G. EBLING G. FABRIZI A. Fll)ANZA D. G RAl'NETTER J.A. GRAll AM B. GUARNIERI A.J. JO UHAR F.11. KEMPER A.M. KLIGMAN N. LOPRIENO S.MADDIN G . MAZZONE C.L. MENEO I ll NI \V.MONTAGNA L. MUSCARDIN N. ORENTREICH E. PANCONESI R. PAOLETTI IV.E. PARISll G. PROSERPIO L. P UG LISI V. QUERCIA IV. RAAB G . RAB BIOSI A .REBORA V. RIZZA G. SALVATORE A.SANNA P. SAN TOIANN I H. SC HAEFER F. SER RI A. SERTOLI A.S TAMMATI I. TADDEI H. TRONNIER V. VALKOVIC !\ID. Prof. of Dcnnat. Ccntrc I fo!<lp. Rcgion:1l dc Bes.1nç:on (F) CChcm. Prof. of Chcm .. Food Dcpan h.t. Sup. Sani1à - Roma ( I) MD. FACP Clc\'cland Cl inie Ohio (USA) DSc. Prof. of Biol. Chcm. Univ. of rvl ilano (I ) MD. Prof. ;md Chainn;m. Dcpart of Dcn11a1. Univ. of Milano (I) l'vlD .. Prof. and Chainnan Dcp~1r1. of l)cnn~u. Univ. of Roma ( I) MD. Prof. ;md Chainn;1n. Dcpart. of Dcnna1. Univ. of Sa~sari (I) CChcm. Prof. :md Chairman. Dcpart. Tcchn. or Commcrcc Univ. or Roma ( I) DSc. Prof. ofCosmct. !PIL. Lyon (I') MD, P rof. :md Chairma n. f)cpart of Ph:nol. An;1t. C:uholic. Univ. or Ro ma (I} DSc. Ph D. P rof. ofZoology Un iv. ofSc hc fficld (G ll ) MD. Pacclria1ic [)crm;1tologis1. C:Hholic Univcrsi1y of Roma (I) DSc. Prof. and Chaìrnrnn. l)cpar1. of Phys iol. Un iv. of Roma (I) PhD. lns1. for C linicoil and Exp. Medicine Praguc (CS) B.Sc. PhD. Dcpt. Dcnmuology Univ. of Penn ~yl vania (USA) MD. Prof. and Chaim 1an. Dcp<in. of Dcnnm. Univ. of Messina (I) M.B.MRSC Bcaconsficld (GB) MD. Prof. and Chaim1:111. Ocp:1r1. of Phammcol. and Tox. Univ. Munslcr (D) MD. PhD. Prof. of Dcnnntol. Unh'. of Pcnn<) l\'ania Philadelphia (USA) DSc. Prof. of Gcnc1ica Univ. of Pi\a (I ) MD. ERCP Clin. Prof. Dcnnatol. Div. Dcnna1. Univ. BR. Columbia. VancoU\'Cr (C) MD. Prof. and Chainnan. Dcparl. of Phannacol. and To:-:. Un iv. of Ca1ania ( I) M D. Prof. and Chaimtan. Dcpan. of Dcnnat. Uni•'. of Bnrì ( I) DSc. Prof. of Dcm1a1. Oregon I lcalt Scicncc Uni,·crsity (USA) MD. P rof. of Dennat. Ccntrc Ho~p. Rcgional IDI Roma (i) MD. Clin. Prof. or Dcnnat. New York (USA) MD. Prof. and Chainnan. Dcpan. of Dcm1a1. Univ. of Fircn1e (I) MD. Prof. and Chainnan. Dcpan. of Phannacol. and Tox. Uni v. of Milano (I) M A. Ph D. BVSc. 1-lcad of Enviromncnml Safc1y Division. Unilcvcr Rcscarch Schan brook (G B) CChcm. Prof. lnc. or Cosmc1. Chcm. Univ. of Torino (I) DSc. Prof. or Pham1acosnosy Univ. of Milano (I) CChcm. Prof. or Chem. Dcpart. of Plwnn. Chcm. lst. Sup. Sanità Roma (I) MD, Prof. ;;md Chairm:tn. Dcp:tr1. of Dcnna1. Un iv. of \Vien (A) MD. Prof. and Chainnan. Dcp:1r1. of l)cn11:11. Univ. of P:ivi:t (I ) MD. Prof. ;md Chainnan. Dcpan. of Dcnn;it. Univ. ofGcnova (I) Ph.D. Pror. o f Biol. Chcm. Univ. of C;.11;;111ia (I ) CChem, Dc pan. ofToxicol. lst. Sup. Sanità Romn (I ) MD. Pror. :md Chainnan. Dcpart. or Mi crobio!. Cathol ic. Univ. of Ro ma (I) MD. P rof. and Chainnan. Depart. of Dcnn:.ll. Univ. or Napoli (I ) MD. P hD. Prof. ;md Chaim1;m. Dcpar1. of Ph annacol. C IRO Sophia-Anlipolìs Valbone (F) M D. P rof. and Chainnan. Dcpart. of Dcnna1. Cathol ic. Uni v. of Roma (I) MD. Assoc . Prof. or Allergie and Occupational Dcnnat. Univ. of Firenze (I) DSC. Dcpart. of Toxicol. lst. Sup. Sanità of Roma (I) B.Sc.• Prof. and Chairman. Dcpart of Phamlacol. Scicncc Univ. of Siena (I) MD. Prof. and Chainnan. Dcpart. of Dcrma1ol. S1ad1ischcn Kliniken of Donmund (D) CChcm. Prof. of Physic Ruder 8()!)ko\•ic' l nst. ofZ.1grcb (Y) GENERAL INFORMATION The JOURNAL OF APPLIED COSMETOLOGY is an international journal devoted to publisching originai papers, reviews and other materiai which represent a useful contribution to research on the ski n and on cosmetics. It is aimed at cosmetic chemists, dermatologists, microbiologists, pharmacists, experimental biologists, toxicologists, plastic surgeons, and alt other scientists working o n products which will come into contact with the skin and its appendages. The Journal is publisched quarterly in English. It is distributed to cosmetic chemists, dermatologists, plastic surgeons, medicai and pharmaceutical schools, medicai libraries, selected hospitals and research institutions throught the world, and by subscription to any other interested individuals or organizations. Statements and opinions expressed are persona! to the respec tive contributors and are not necessarily endorsed by the Editor(s), Advisers, Publishers of Distributors of this Journal. COPYRIGHT Submitted materiai must be the originai work of the autor(s) and must not have been submitted for publication elsewhere. By submitting a manuscript, the authors agree that the copyright for their articles is transferred to the publ isher if and when the article is accepted for publication. None of the content of this publication may be reproduced in whole or in part, translated, stored in a retrieval system, or transmitted or distributed in any form or by any means (electronic, mechanical, photocopy, recording or otherwise) without the prior written permission of the Publishers. Sections of Journal The following sections wi ll be featu res of the Journal: Originai Laboratory Studies: descriptions of originai investigative laboratory research in cosmetics and related areas. Special Reports: Items of special interest to the readers, including reports on meetings, societies, legislation, etc. Generai Articles: scientific articles of generai interest to our readers will be considered for publication. These articles should be concerned with newer developments in such related fields as dermatology, biology, toxicology, etc. Short Communications: the lenght should not exceed 5 typewritten pages with not more than 3 figures included. Headings ("Materials", " Discussion", etc.) as well as Summaries are to be omitted. If accepted, these submission will appear in print in a very short time. Letter to the Editor: comments on Journal articles are invited as well as brief contributions on any aspects of cosmetic science. Letters may include figures, and/or references, but brevity is necessary. Guest Editorials: concise, authoritative, substantiated commentary on specific topics of contemporary interest. Book Reviews: book and monographs (domestic and foreign) will be reviewed depending on their interest and value to subscribers. Send materiai for review to the Editor, Dr. P. Morganti. No such materiai will be returned. Address: ali papers should be submitted to: Dr. P. Morganti INTERNATIONAL EDIEMME Via Innocenzo XI, 4 1 00 165 Rome - Italy Tel. 06/637.87.88 INFORMATION FOR AUTHORS Papers must be submitted in Eng lish. Authors whose mother tong ue is not English should arrange for their manuscripts to be written in proper English prior to submission. Procedure of Submission of Manuscripts: submit three copies of both the manuscript and ali illustrative materiai to the above address. Organization of the Manuscript: in vestigative studies should be organized as fo llow: title, abstract page, introduction, materiai and methods, results, di scussion, acknowledg ments, references, legend for fi gures, tables. Ali pages sho uld be numered consecutively starting with the abstract. The entire manuscript is to be typewritten, double-spaced, and with 3 cm margins. Trade names must be capitalized: the common name for compounds may be used if the formai chemical name as established by international convention is given after the fi rst use. Any abbreviations other than those which are generally accepted must be defined. In the text, references to dual authors wi ll use both surnames throughout. For multiple authors, use the surnames of ali authors at the first reference and only the first author followed by "et al." thereafter. Please mark in the margin of the manuscript the desired position of the figures and tables. To allow faster publication only set of proofs will be furni sched to the author including the figures and tables in their final position. • Title page: list the title, name(s) and degree(s) of author(s), clepa11ment(s) and institution(s) at which the work was done, ci ty, state, and posta i code. Any preliminary report or abstract of the work should be referred to as a footno te to the title. Summary: each paper must be headed by an English language title of not over 70 characters (including spaces) suitable for use as a running head and must also be proceded by an English summary not exceeding 300 words typed double-spaced. The summary will include statements of the problem, method of study, results, and conclusions. Since this summary will be used by astracti ng journals, it must be self-explanatory and should not inlcude abbreviations, footnotes, and references. Footnotes: should be listed consecuti vely at the bottom of the page on which they fa ll , designated by the fo llowing symbols in o rder *, +, + , §, II, **, etc. Key Words: key words for computerised storage and retrieval of information should be incorporated in the summary. References: the references have to be abbreviated as listed in the Index Medicus. The style of the references must conform to the examples g iven below: I) Robbins CR, Kellych ( 1970) Aminoacid compositi on of human hair. Text Res J 40:891-896 2) Strehler BL (1977) Time, cells and aging 2nd edn . Academic Press, New York 3) Ebling FJ, Rook ( 1972) Ciclic activity of the foll icle. In: Textbook of dermatology 11 , Blackwell, Oxford, p. 1567-1573. lllustrations: fi gures should be numbered consecuti vely using Arabic numerals Tables should be numbered consecutively, using Roman numerals. Al! photographs should be black and white, glossy and unmounted. The number and size of illustration should be restricted to the minimum needed to clari fy the text. Authors requiring extra space for illustrations will be charge according ly. This is also the case for color illustrations. Ali figures, photographs, graphs, or diagrams should be submitted on separate sheets . Animai Experiments: descriptions of animai experiments should include full details of the types of animai used (inbred, etc.) and the conditions under which they were kept (standard diet, etc.). Trade Names: ali common cosmetic ingredients should be referred to by their generic names, as indicated in the latest edition of CTFA Cosmetic Ingredient Dictionary, and the European Pharmacopeia. 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The Editor(s) and publisher, d isciaim any responsability or liability for such materiai and do not guarantee, warrant, or endorse any product or service adverised in this publication nor do guarantee any claim made by the manufacturer of such product or service Quarterly Review of Cosmetological Dermatology INFO RMAZIONI PER L.ABUONAM ENTO L' tibbonamcmo annuale comprende quauro numeri. È possibile ottenere ::ibbonamcmi a prezzo ridono da pane dci ricercatori che lavorano presso b1ituti che abbiano sot1oscrit10 almeno un abbonamcn10 a prezzo normale. L" Editorc potrà fornire a richiesta n0li1ic più dcttagli•lle. 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Dclctc as ncccssary: AM ERIC AN EXPRESS O DINERS CLUB - Card Numbcr Expira1ion da.1c . .. ... ....... ........................... . ( Pleast! Prim) Na01e Address City - - - - - - - - - - - - P ostal Code Country ____~---------~--------~~~----~ STAMP spett. Direzione "JOURNAL OF APPLIED COSMETOLOGY" INTERNATIONAL EDIEMME Via Innocenzo Xl, 41 00165 ROMA (ITALY) STAMP Spett. Direzione "JOURNAL OF APPLIED COSMETOLOGY" INTERNATIONAL EDIEMME Via Innocenzo Xl, 41 00165 ROMA (ITALY) journa~Iof appie 1 cosme ology Trimestrale di Dermatologia Cosmetologica Quarterly Review of Cosmetic Dermatology Contents Generai Articles 1 Use and efficacy of urea in dermatologica! preparations W. Wohlrab 9 Urea from the chemist's point of view R. P. Raab 15 Biochemistry, pharmacology and therapeutic use of urea W. Raab Originai Laboratory Studies 19 Changes in stratum corneum after urea application to human skin in vivo. Electron microscopie investigation G. StOttgen 24 Book Review XIX Anno unc ements 4th lnternational Meeting of lnternationa l Society of Cosmetic Dermatology "Progress in Cosmetic Dermatology: Science and Safety" Rome - ltaly October 30-November 2, 1991 Preliminary Program l 8th World Congress of De rm atology J. Appl. Cosmetol. 9. 1-7 (Jonuory - Morch 1991) USE ANO EFFICACY OF UREA IN DERMATOLOGICAL PREPARATIONS W. Wohlrab Department of Dermatology, Martin-Luther-University, PSF 302-D-4010 Halle Received: October 26, 7989; Presented at at 3rd lnternational Congress on Cosmetic Dermatology "Progress in Cosmetic Dermatology" - 27 - 29th October 1989. Wien Key words: Urea: Penetration: Water-binding capacity: Topica/ therapy. _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Synopsis The bas is of the effects of urea on the human skin is its penetration kinetics into different skin layers. A strong vehicle dependence can be estabilished. Therefore wide differences are found in the duration and intensity of increased water-binding capacity after application of different urea containing emulsions. For therapy to increase the hydration and water-binding capacity in the homy layer of diseased skin preparations with IO% urea are more suitable than those containing 2% or 5% urea. For cosmetic preparations, the hi gher concentrations of urea are inappropriate, lower ones are sufficient. By altering the fu nctional structure of the homy layer and increasing of drug liberation from ointment bases, urea is one of the most effective penetration promoters. An increased penetration rate of some corti costero ids, dithranol and other drugs in human skin. The resulting penetration has two possible im plications for topica! therapy: - an increased therapeutic effect for any given concentration of an active constituent - the attainment of a g iven therapeutic effect with a reduced concentration of the active ingredient. ------------------Riassunto G li effetti esplicati dall'urea sono connessi alla sua penetrazio ne attraverso i differenti strati dell'epidermide e, quindi , direttamente dipendenti dal tipo di veicolo utilizzato. Per questi motivi sono state riscontrate differenze nella durata e nella intensità della capacità del prodotto di legare acqua in dipendenza del tipo di emulsione. Per incrementare l'idratazione cutanea e la capacità di legare acqua della cute affetta da patolog ie si sono dimostrate più efficaci concentrazioni di urea del 10% rispetto a concentrazioni del 2 o del 5%. Per uso cosmetico sono più adatte e sufficienti concentrazioni basse di urea. L'urea può essere cons iderata una delle sostanze più atti ve nel promuovere la liberazione dei farmaci dai veicoli e, quindi , il loro assorbimento. Facilita, perciò, l'attività dei corticosteroidi, del ditranolo e di molti altri farmaci. Queste sue caratteristiche ne consig liano l'uso terapeutico in due direzioni diverse: -per incrementare l'effetto terapeutico di una data concentrazione di farmaci resi per questi motivi ugualmente attivi a concentrazioni più basse. Use and efficacy of urea in dermatologica/ preparations The use of urea in topica! therapy and in cosmetics has undergone a revival in recent years (I , 3, 4, 11 and others). Some reasons fo r this can be Jisted as follows: 1. By intensive basic research many properties of urea have bee n d iscove red a nd precise ly defi ned. At the same time, the conditions for the the rape utic uti li zati on of these properties e.g. problems of stabilization, have been delineated. fondamenta! differences between w/o and o/w e mul s ions (7), and the s e y ie ld d ifferen t therapeutic effects. Urea penetrates the horny layer of huma n skin more qu ickly from o/w e mul sions tha n fro m w/o em ulsions (Fig. I). It should be noted that, at about 80%, the bulk of the urea whi ch has penetrated is found in the upper horny layers. 103 2. In topica! therapy inc reasing use is made of pharmacok inetic information. The equa ! significance of the properties of the active substances and of the veh icle, the condition of the ski n, a nd their mutua i interactions, are not o n ly recognized but also increasingly util ized a bas ic far overall therapeutic activity. Pha rmaceutical formu lations are selected and optimized in such a way that a desirable concentration/time profile is achieved for the substance in the appropriate skin layer. 5 10 15 (/) - 20 Principles of the action of urea on skin The pe netration kine tics of urea, i.e. how much urea, in relation to exposure time, pene trates into individuai skin laye rs after external app lication, are of d ec isive importance to the achievement of its effects. In relation to the vehicle, the penetration kinetics of urea show 2 30 min Q. ·;:: ( /) o (/) I- Q) .o E ::i z 5 10 15 20 ' 300 min ' 5 10 15 3. The properties of urea itself make it ideai for external use, as it is a natural moisturizer and is well to lerated. As a physiological substance it is the end product of protein metabolis m. In human skin its concentration is I% and it is excreted in sweat in considerable quantities. After ex ternal or sys temic adm inistration it is not metabolized. No side effects, in particular non cases of sensitization or photosensitization, have so far been repo1ted unde r therape utic conditions. dpm - cm·2 104 105 20 1000 min "-~~~~~~~~~~~~~~ ffGUREl Oistribution of urea in lhe horny /ayer of human skin affer external applicalion of 10% urea conlaining preparations. •- - -• w/o-emulsion (Ungi. Alcohol. Lanae aquosum. Pharmacopoea GDR) o - o o/w-emulsion (Ungi. emulsiticans aquosum. Pharmacopoea GDR) The s teep concentration gradient is la rgely maintained when o/w emu lsions a re used, even after as long as I000 min. In contrast, the penetration of urea from w/o em ulsions is noticeably smaller after short exposure. The concentration gradient within the horny layer decreases so that after 1000 min approximately equa! urea concentrations can be measured throughout the stratum corneum. Thi's resul ts in different urea concentrations in the epidermis and dermi s (Fig. 2), which are apprec iably higher for w/o emulsions. Overall , however, the penetration of the lower epidermis and dermis are sma ll in comparison with that of the horny Jayer, regardless of the emulsion used. W Wohlrab o 103 C/) C/) ..... Q) _o E => :i e ~ (f) o ..e a_ Q) o 160 200 400 600 800 1000 104 . 5 10 15 20 z -E - These diffe re nces in the course of penetration and he nce in the concentration/ time profile of urea in the indi viduai skin layer provide for different degrees of efficacy. Different emulsions can be used according to whether the urea is to act on the functional skin structure (e.g. hydration and water-binding capacity, keratolysis, inhibition of proliferation, alleviation of itching, etc.) orto aid penetration by other products. dpm - cm- 2 C/) a. ·;:: 105 r·-:?_..;/_____ . ----o:.);!· ,. ------: t• • ·t·· Epidermis I ·''· Dermis /o What is the necessary concentration of urea in the vehicle? I • I' ·I: . ,.. o Horny layer I • I• ·1. Penetration time: 300 min ' - - - - - - - - - - - - - - - - FIGURE 2 Distribution of ureo in humon skin ofter externol opplicotion of 10% ureo contoining preporotions. • - - -• w/o-emu/sion (Ungt. Alcohol. Lonoe oquosum, Phormocopoeo GDR) o - o o/w-emulsion (Ungt. emulsificons oquosum. Phormocopoeo GDR) From the findings so far di scussed, it is clear that the decisive factor in therapeutic activity is not th e conce ntra tion of urea in the appli ed ve hicle but rathe r the quantity of urea whi c h penetrates into the indi viduai skin layers, i.e. the concentration/ time profile achieved. It has be Table I CONCENTRATION OF UREA PENETRATING TO THE STRATUM CORNEUM (SC) OF HUMAN SKIN IN RELATION TO THE CONCENTRATION OF UREA IN THE VEHICLE (9) Veh icle: W/0-emulsion (Ungt. Alcohol. Lanae aquosum AB-DDR) Pene tration Pe riod (min) Urea Conce ntration (%) applied Urea concentration (mm) in the se 30 2 5 29,9 103, 1 2 12,6 10 ------------------------------------------------------------------------------300 2 5 10 48,3 145,7 449,9 -----------------------------------------------------------------------------1000 2 5 10 95,8 23 1,6 602,9 3 Use and efficacv of urea in dermatologica/ preparations noted that, at around 80%, the bulk of the urea wh ic h penetrates is situated in the outer horny layers (Tab. 1). When vehicles containing 2% or 5% a re used the urea concentration necessary fo r normai human stratum corneum cannot be reached. To increase the water-binding capacity in the horn y layer of di seased skin products containing 10% of urea are more suitable from th e th erapeuti c point of v iew (9) . High urea concentrations (over 2-3%) a re not, however suitable for cosmetic use without medicai supervision. lnfluence of the vehicle on the water-binding capacity due to urea. Corresponding to the described differences in penetration, depending on the vehicle and the urea concentrations used , the re are also variations in the effectiveness of the urea-containing basic skin products to increase the water-bind- "' 104 E (.) E o.. "O 103 t.. • • W/O - emulsion + 10% urea W/O - emulsion without urea :~I~-·T-r-iti-at-ed wa-t-er_ _ __ 1~~--~--------~- 30 300 1000 '----------------FIGURE 3 lnfluence of ureo on the woter-binding copocity of the humon horny loyer (10). Vehicle: w/o-emulsion (Ungt. Alcohol. Lonoe oquosum. Phormocopoeo GDR) lobeled with tritioted water. ing capacity of th e stratum corn eu m (5, 6). When the urea is used in o/w emulsions or lotions, a hig h degree of hydration is q ui ck ly reac hed (i mm ediate effec t), but th is fairly quickly declines (Fig. 3). In contrast, with w/o emulsions there is a more marke t and longer-Iasting inc rease in waterbinding capacity. Table Il WATER-BINDING CAPACITY OF HUMAN HORNY LAYER AFTER APPLICATION OF UREA CONTAINING PREPARATIONS (10). Application: I Omg of urea containing preparati on labeled with 5 µCi tritiated water at 4 cm2 skin surface. preparation Basodexan (R) Ointment Basodexan (R) Cremé Basodexan (R) Soft Carbamid-Cremé(R) Elacutan-F(R) Elacutan-W(R) Excipial(R)-U-Lotio HTH(R) 4 urea concentra tion Horny Iayer dpm/cm2 after 300 1000 min (%) 30 10 IO 10 12 IO IO 2 IO 5422 ± 521 8 104±514 10606 ± 678 8666 ± 426 3968 ± 275 7 185±376 6804 ± 248 12011±528 2478 ± 205 1386 ± 169 542 ± 98 12 14 ± 100 994 ± 63 426± 72 388 ± 26 568 ± 59 902±5 1 472 ± 34 185 ± 22 475 ± 28 678 ±74 183 ± 19 126 ± 24 223 ± 63 W Wohlrab If o ne ex am in es these bas ic mec hani sm in re lati on to the various comme rciai urea-containing bas ic skin products, la rge differences are found in the action o n th e w at e r-bindin g capacity of the stratum corneum (Tab. 2). These di ffe rences a re evide ntl y not primarily depende nt on the urea concentration used but on the vehic le ( I 0) . lnfluence of urea on the penetration of other products Urea promotes the release of various drugs from their base, a nd in additio n it is a very effecti ve promote r of pene tration o f vari ous active substa nces ( I , 3, 4, 11 ). Essenti a ll y, the promoti on of drug penetration by urea can be ex plo ited in two ways (8) : I . to improve therapeut ic efficacy at the same conce nt rati on of acti ve substance and 2. to achie ve the same the rape utic efficacy with a conside rabl y lower conce ntration (Fig. 4). The optimization of the therapeuti c efficacy of oth e r dru gs by urea has bee n de mons trated above ali with glucocorticoids (e.g. Hydrodexan (R), Hycozon (R ), A lphade rm (R), etc .) an d dithranol (e.g. Psoradexan (R)), with impressive evide nce from nume rous clinica! studies. With respect to hydrocorti sone, it has been shown that when low concentrati ons of urea are used enhancement of pe netration is barely appare nt, whereas with a urea content of between 5% and I 0% there is a partic ular increase (Fig. 5). HC (µmol) 90 70 50 30 10 o 2 5 7 10 1s Urea(%) ' - - - - - - - - - - - - - - - - - FIGURE 5 Dependence of hydrocortisone penetrotion into epidermis of humon skin on ureo concentrotion ond used vehicle. Penetrotion time: 300 min. Hydrocortisone concentro tion: 1% • - - -• w/o-emulsion (Ungt. Alcohol. Lonoe oquosum, Phormocopoeo GDR) o o o/ w-emulsion (Ungt. emulsificons oquosum, Phormocopoeio GDR) e ~ Cl) o ..e a. a.i o 800 1000 Penetration period: 300 min - ~-~ - 1% HC 1% HC + 10% Urea 0,5%HC + 10% Urea ~---------------FIGURE Distribution of hyd rocortisone (HC) in humo n skin ofter externo l opplicotion (8). 4 Whe n the urea concentrations are rai sed further, no fu rther decisive c hanges are de tectable. In this connection o/w emulsions and w/o e mu lsions basically act in the same direction, but w/o e mulsions have a conside rab ly greate r penetration-promoting effect. On the bas is of these data hydrocortisone, the de te rmination of the penetration kinetics of the g lucocorticoid and of the urea in each vehicle is indispensable for mak ing use of the penetrationpromoting acti on of urea in the development of 5 Use and efficocy ot ureo in dermatologica/ preporotions glucocortic oids fo r external use (8). The urea and g lucocorticoid conce ntrations can then be optimi zed. Less attention has so far been paid to the possibili ty of using the pene tra tion-promoting action of ure a to achie ve a particul ar therapeutic efficacy with a considerably red uced quantity of g lucortic o id. One reason is very probab ly the w id e ly prac ti se d d il u t io n of pro pri e t a r y glucocorticoid formulations. In 1984 Miiller (2) summari zed the reasons fo r this procedure and its proble ms and risks in a ve ry inform at ive review. T he examp le of hydrocortisone shows ve ry c lea rly th a t a fte r red uc tio n to 0,5 % th e qua ntity whi ch penetrates e.g. into the e pidermis ca n be reduced by 75-80 % (Tab. 3). In contrast, when vari ous qua ntities of urea are added, a co nce ntr a t io n -de p e nd e nt p ro m o ti o n o f pe netration is detectable, so that the form ulation beco m e s i d enti ca! in efficacy wi th a I % hydrocortisone produc t in whi c h the re is no urea. Viewing this subject as a whole, we still know too little about the pharn1 acological propertie s of urea fot ex te rna l use. Autom atic procedu res in the a pplicatio n of urea in externa l therapy and exam ination of th e prope rti es of urea in iso lation th erefo re promise little success a nd sho uld be avoided. Table lii INFLUENCE OF UREA ON THE PENETRATION OF REDUCED HYDROCORTISONE CONCENTRATIONS INTO HUMAN SKIN (12). Vehicle : W/0 -emulsion (Ungt. Alcohol. Lanae aquosum, Pharmacopea G DR) HC = hydroco rti sone; u+ = Urea. Preparati on horn y layer (mmo l) l ,0 % HC 0,5% HC 0,5% HC + 5% u + 0 ,5% HC + 10% u+ 0 ,5% HC + 15% u+ pene trat ion time (min) 30 300 13,9 2,9 8,5 12 ,5 12,8 16 , l 3,9 10,0 13,8 14,0 ----------------------------------------------------------- -------------------epidermis (µm ol) l ,0% HC 0,5 % HC 0,5%HC + 5% u+ 0,5% HC + 10% u+ 0,5% HC + 15% u+ 6 12,8 2, 1 6,8 10,2 l l ,9 23,2 5,7 11 ,0 19 ,9 20,7 W Wohlrob References 1. Horsch W., Wolf B. (1985): Harnstoff. Eine Ùbersicht unter Besonderer Beriicksichtig ung seine r pharmazeutische n Verwendung und Analytik. Pharmazie 40, 665-676. 2. Muller K.H.(1984): Corticoid-Verdiinnungen. Zbl. Haut-und Gesch/echtskra11kh . 149, 853-86 l. 3. Mu ll er K.H., Pflugshaupt Ch. (1979): Harn stoff in de r De rmatolog ie. Zbl. Ha ut-u nd Geschlechtskrankh. 142, 157-168. 4. Muller, K.H., Ch. Pflugshaupt (1989): Harnstoff in der D ermato logie. II. Ergiinzende Literaturiibersicht. Hautarzt 40, Suppi. IX, I 3- 19. 5. StUttgen, G. (1988): Der Begriff "Trockene Haut" aus patho-physiologischer Sicht.Z. Hautkr. 63 (S uppi. 3), 7- 11. 6. Thiele F.A.J.,Reay D.A.,Mali J.W.H.,De Jongh G.J. (1981): The water balance of the horny layer and the functional charactericstics of the atrichia! sweat g lands of human skin. In: Handbuch der Haut-und Geschlechtskrankh., Erga nzungswerk , I. Band, Tei l 48; Normai a nd Patho logic Physiology of the Skin. Hrsg.: Stlittgen, G. Spie r, H.W. und Schwarz, E.: Berli nHeidelberg-New York: Springer-Verlag 1981. 7. Wohlrab W. (1984): Vehikelabhangigkeit der Harnstoff-Pe netratio n in die me nsch liche Haut. Derma/otogica 169, 53-59. 8. Wohlrab W. (1984): The influence of urea on the penetration kinetics of topically applied corticosteroids. Acta Dermato-Venereo/. (Stockh.) 64, 233-238. 9. Wohlrab, W. (1988): Welche Harsnstoffkonzentration ist fiir die externe Therapie notwendi g. Dermatol. Mon.schr. 174, 94-98. 10. Wohlrab, W. (1988): Der EinfluB von Harnstoff auf die Wasse rb indun gs kapaz itat der me nschliche n. 1-lornschicht. Dermatol. Mon.schr. 174, 622-627. 11. Wohlrab, W. (1989): Bedeutung von Ha rnstoff in der exte rne n Therapie. Hautar:t 40, Suppi. IX, 35-4 1. 12. Woh lrab W., Taube K.M., Kuchenbecker I. (1990): Penetration und Wirksa mke it von Hydrokortison bei reduzie rter Konzentration im Vehikel. Z. Hautkrankh. 65, 534-537. 7 J. Appl. Cosmetol. 9. 9-13 (January - March 1991) UREA FROM THE CHEMIST'S POINT OF VIEW Regina P. Raab, M.D. 2nd departme nt of Dermatology Vienna University Medicai Sc hoo l. Austria Received: October 26, 7989: Presented at 3rd lnternational Congress on Cosmetic Dermatology "Progress in Cosmetic Dermatology" - 27 - 29th October 7989, Wien Ke y words: Urea : Chemistry; Ma nufac ture; Decomposition; Stabilization: Recommende d Concentrations _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Synopsis Urea is a colourless and odourl ess tetragona! c rystal. Due to its molecular struc ture (dipolaric) it can easil y be disso lved in wate r, whereas it is almost inso lub le in nonpolar substances such as c hl orofo1m or ether. In solu tion, urea undergoes a decomposition to carbon dioxide and ammonia. A so-called "sand pape r effect" may occur, especiall y in pre parati ons containing higher urea concentrations caused by the phe nomenon of recrystallisation. T he re fore topi ca! produc ts with urea require stabil isati on (eithe r with triacetin, lact ic acid or polysaccharides). Non stabilisecl urea contain ing pre parations can only be used safely fo r periods of up to six weeks (the stabilised preparations can be stored for two or even three years). In conclusion it can be said th at urea containing fo rmulations fo r cosmetic and/or de nnatological purposes have to be developecl with great care to provide perfec t results. ------------------Riassunto L'urea é un a sostanza cri sta ll ina e inodore, facil mente solubi le in acqua e praticamente insolubile nei solventi a polari quali il cloroform io e l'ete re. Una volta discio lta l'urea si decompone fac ilmente in anidride carbonica ed ammoniaca. Data la sua poca stabilità in soluz io ne i pre parati topic i a base di urea de bbo no essere ben stabil izzati (s ia con ac ido lattico che con poli saccaridi). S i deve fare a nc he molta attenzione alla sua concentrazione di uti li zzo per evitare il fe nomeno d i ri crista ll izzazione che provoca il cosidetto "effetto sabbia" ben noto ag li utili zzatori abitua li . In conc lusio ne si può affermare che le preparazioni cosmetiche o dermato logic he a base di urea debbono essere form ulate e controllate con grande c ura. 9 Urea from the chemisf's point of view lntroduction Decomposition of urea <Fig. 1> Jean Rouelle (1718- 1778), a french apothecary, di scovered urea as a n a tu ra l co ns titue nt of human urine in 1773 ("Identification d ' une sub stance savo nne use da n s !' uri ne"). Friedri cli Wohler ( 1800- 1882), M.D . and chemist, succeeded in synthesizing urea from a mm onium cyanate. He therefore proved tha t no mysti cal "v is vita lis" is necessary to synthesise organic materials from inorgan ic precursors. Once in so lution , urea decom poses and, in simpl e term s, the following reactions occur. First U is con verted in to am moni um cyana te. The equilibrium lies completely on the side of the unc hanged U . In the subseq ue nt reaction ammonium cyanate is hydrolytically split. Othe r U mo lecules then fo rm a mmonium cyanate in orde r to maintain the e qu ilibrium of the fi rst reaction. Ammonium cyana te is spli t into two molecules of ammonia and one molecule of carbonic acid. Carbonic ac id is a weak and instable ac id (W + HC03 ~ H2C0 3 <=> C02 + H20), the two mo lecules of ammonia react as proton (W)- acceptors. Manufacture and chemistry of Urea: Urea (U) is the d iamide of carboni c ac id. It is a co lo urless, odou rless (or nearl y odo urless), slig htly hyp ogroscopic pri sm ati c crys talline substance w ith a cooling saline tas te (2) . T he world prod ucti on of urea is mainly used in fertilizers a nd for the sy nthesis of plasti cs (altoge the r 4 0 mi llion tons in 1980 ). These large amo unts of U a re ma nufactured fro m a mm o ni a a n d ca rb o n dio x ide unde r h ig h press ur e (100-200 at m ) and hi g h te mperatures ( l 70-250°C). In the la borato ry U is stili syn thesized by the me th od of Dr. Wohle r.. Apa rt f,ro m th e m a ny fa voura ble effects of topica! urea, this substance is c heap. 1 kg of Urea p ura o f th e q u a lity s pec ifi e d in t he Austria n pharmacopoeia wo uld cost less tha n 50 AS . Due t o its ability to fo rm in tra m o lec ul a r di poles, U rese m b les t he wa te r mo lec ul e . The refo re it readi ly di ssolves in p o lar solvents suc h as wate r or alco ho l but it is a lmos t in s olubl e in n o npo l ar m e d i a s u c h as c hlorofo rm or ethe r. U is a weak accepto r of proton s a nd wo uld g ive in water a solution with a pH of 7,5 , at least theoretically. Dev iations occur due e ither to the carbon dio xide content of wate r or to impurities and decomposition of U itself. 10 DECOMPOSITION OF UREA Urea Ammoniumcyanat Ammoniumcyanat Ammonia + carbonic acid ' - - - - -- - - - - - - - - - - FIGURE 1 The refore the pH constantly increases. Some factors such as the steadi ly increasing pH, raising of the temperature and open storage, which pennits the escape of the produced ammonia and carbon dioxide, enhance the decomposition. Open storage (and high temperature in addition) favours evaporation of water. Tue result could be a recrystalli zation of U. The risk is greate r with t he higher initial concentrations of U. The c rystals act like sand on the skin and cause irritation. R. P. Raab Therefore topical preparations containjng urea should be made airtight after each usage and stored at normai room temperature or below. Before application it should be made sure that no sandiness has developed (4). Stabilization of Urea: T he a bove me nt io ned fa cts expla in w hy indu s tria lly prod uced top ica l preparations contai nig urea must be stabi lized . ·stabi lizati on redu ces and de lays di s integratio n an d keeps the pH consta nt over longe r periods (2). One possibi lity fo r stabili zing U is the addition of triacetin. Triacetin is an ester of glycerol with three molecules of acetic acid. As soon as pH inc reases, the es te r bo nds are hyd ro lyticall y spli t and the released acetic ac id will keep pH constant. Anothe r possibili ty is the add ition of lactic acid, wic h is as effective as acetic acid. Moreover, lactic acid is part of the NMF of the skin and will therefore increase one of the effects of U. However stab ili za tion w ith lactic acid ca n lead to burn ing sensations. At presen t the mos t sophisti cated method of stabil ization is the adsorpti on of U to polysaccharides (for instance corn or rice starch). There are no problems with locai to le rance, and the p H in these formulat ion s can be adj usted as desired. Urea containing preparations tor topica/ use upon special p rescription: Some problem s arise if one prescribes an U co n ta ini ng top ica l p reparation. General ly spoke n this task is easier the lower the requi red · U concentrations and the hig he r the required water content are. Before introducing U into the formulation th e c rysta ls have to be pu l- verized. The use of an ointme nt mili will cause disappearance of sandi ness (4). For cosmetic and dermatologica] purposes such as augmentation of the skin -moisture, generai skin protection and therapy of scaly lesions, 35% U in an O/W em ul sion are recomme nded (5,6). This will have an immediate effect on the upper horny layers (Fig. 2 and 3). UREA IN O/W Urea purae 5,0 NaCI 5,0 Tween 80 20,0 Aquae dest. 40,0 Vas. alb. ad 100,0 ....___ _ _ _ _ _ _ _ _ _ _ _ _ _ FIGURE 2 UREA IN O/W Urea purae 3,0 Allantoin 0,2 Karion F liqu. 3,0 Vas. flav. 10,0 Lanette N 15,0 Guajazulen 25% Aquae dest. 0,04 100,0 .....___ _ _ _ _ _ _ _ _ _ _ _ _ _ FIGURE 3 For the treatment of pronounced dermatologica! disturbances such as psoriasis vulgaris, different forms of ic hthyosis, atopic dermatitis a nd extremely dry skin, 10 % U in W/0 shou ld be applied (5,6). U in W/0 has not such a distinct immediate effect but has a longer lasting beneficiai action due to its deeper pe netration into the 11 Urea from the chemist's point of view ski n (Fig. 4). For painless onychol ysis, 40% U concentrations are necessary. The surrounding skin should be protected with a paste. UREA IN W/0 Urea purae NaCI Aquae dest. Ungt. aie. lanae aqu. ad 10,0 10,0 20,0 100,0 ...___ _ _ _ _ _ _ _ _ _ _ _ _ _ FIGURE 4 After 5-1 O days of occlus ion the nai l can be removed (7). As shown in Fig. 5, U in this case is incorporateci into a vehi cle, which consists only of va rio us lipids . It is not di ssolved but merely s uspended. Therefore sandiness is inevitable. No improvement wi ll be brought about by oi nt me nt mill s as th e ir use w ill lead to separation of the differe nt parts of the veh icle (4). ONYCHOLYSIS WITH UREA Urea purae NaCI Aquae dest. Ungt. aie. lanae aqu. ad 40,0 5,0 20,0 100,0 Oeelusion (5-10 d) ...___ _ _ _ _ _ _ _ _ _ _ _ _ _ FIGURE 5 lndustrially produced urea containing preparations tor topica/ use: lndustrially manufactu red products ·have some di stinct advantages over those upon special prescription. They have a g uaranteed stability over 2-3 years on an average, w hereas the prescribed products can on ly be used fo r 4-6 12 weeks. T he quality of ma nufactured creams, ointments or lotions is good and constant. Urea itself shows some antimicrobial action (5). T herefo re little or no preservative need be added, and it is well known, that preservatives are rathe r disadvantageous from the allergological po int of view. In summary it can be said, that urea is a somewhat difficult substance to incorporate into good and stable topica! formu lations. Therefore urea containing preparations for cosmetologica! and dermatological purposes need to be developed with the utmost care to guarantee perfect results. R. P. Raab , References 1. Braun-Falco O, Plewig W. (1984): Dermatologie und Venerologie, Springer Verlag Ber/in Heidelberg - New York. 3rd Edition, p. 1011 2. Horsch W. et al (1985): Harnstoff - Eine Ù bersicht unter besonderer Be ri.icksichtig ung seiner pharmazeutischen Verwendung und Ana lytik. In: Die Pharmazie, Heft 10, p. 665-676 3. Òsterreichische Apothekerkammer (1988): Neues Forrnulariurn Austriacurn 4. Raab R. (1989): Harnstoffrezepturen. In: Der Hautartz 40, Suppi. 8, p. 80-8 1 5. Wohlrab W. (1988): Zur Verwendung von Harnstoff in der Dermatologie. D. Derm. 36: p. 528537 6. Wohlrab, W. (1988): We lche Harsnstoffkonzentration ist fi.ir die externe Therapie notwendig. Dermatolog. Monatsschrift 174, 94-98. 7. Zesch A. (1985): Externa, Galenik, Wirkungen , Anwendunge n. Spri11ger Verlag Ber/in Heide/berg - New York 13 J Appl. Cosmetol. 9, 15-17 (January - March 1991) BIOCHEMISTRY, PHARMACOLOGY ANO THERAPEUTIC USE OF UREA W. Raab (Allergy Clinic "City", Vienna, Austria) 3, Walfischg asse A- 10 1O Vienna, Austria Received: October 26, 7989. Presented at 3rd lnternational Congress on Cosmetic Dermatology "Progress in Cosmetic Dermatology" - 27 - 29th October 7989, Wien Key words: Urea: Safety; Preservatives; Atopic Eczema _________________ synopsis Modem de rmato logy looks mo re a nd more closely in to "old " substances wich proved to be effecti ve and safe. In additi on, most of them are much cheaper than the new compounds. Urea is one of the o ld substances whic h were used more and more often in topica( therapy of dermatoses, either alone or in combination wi th a steroid, anthralin, reti no ic acid or salicylic acid. In this paper, biochemistry a nd pharmaco logy of urea with special refere nce to its topical applicat ion were outlined. In many dermatbses, urea containig preparations may be successfull y appl ied. Lasty, the possibilities of urea in cosmetology are briefl y di scussed. Riassunto L'urea é una de lle sostanze più vecchie di uso dermato logico, utili zza ta in te ra pi a da so la o in associazione con steroidi, atralina, ac ido retinoico e acido salicil ico. Viene desc ritto l'aspetto biochim ico e farmacologico de ll'urea in relazione sopratutto al suo uso topico. In molte dermatosi le preparazioni a base di urea vengono utilizzate con grande successo. Infi ne ne vie ne discusso il suo uso cosmetologico. 15 Biochemistry, pharmacology and therapeutic use of urea lntroduction Urea (carbamide, the di amide of carbonic acid) may be found in ali organs, ti ssues, and body fluids. Phys iologicall y, urea is present on the skin surface, too, as a compone nt of the hydrolipid e mu lsion. Urea here stems from sweat (content 0 .4% urea) and from keratin ization (end product of a rginine degradation). In fo rm e r times, urea ma inly was used as a d iure ti c a nd a n a nti e d e m a dru g . D oses amounted to I 5 g per day orall y or I.O g/kg/d intravenously. Urea was we ll tolerated even in these hi gh doses. Fro m the beginnin g o f the fo rties, urea was used for de rmato logica! th e rapy in the fo rm of creams and o intme nts (1, 2, 4 ). Numero us experime ntal in vest igations proved its valuab le the rape uti c acti o ns . In th e last years, urea is al so inc reas ing ly fo und in co sme tic pre para ti ons . In Decembe r 1988, a symposium was he ld in S al z b urg on " Urea in d e rmatolo gy" . Th e proceedings of thi s confere nce contain a li the documentation on this topic (2). Dermato-toxicology of urea The topica! use of urea neve r provokes systemic resorptive effects as urea by itself is an atoxic substance. On healthy skin , urea may be applied in concentrati ons up to 20%. (Due to c hemical factors, such concentrations a re not easy to reach! ). On inflamed skin , concentrations of urea should be limited to 2 or 10%, depending upon the state of the lesions. Urea in a 40% concentration may be u sed for c h e mi ca l on yc hol ys is, e.g . in onychomycoses. Urea lacks sensitizing a nd photodynami c acti vities. Urea is color- a nd odorless and does not stain either the skin or the linen. 16 Pharmacological acfivities of urea upon topica/ use Applied ex te rna lly, urea exerts a variety of derma tologicall y and cosme tologically important actions: Moisturizing action: Urea binds water by includi ng it into its c rystal struc ture. In a concentration of 70%, urea is an important component of the natural moisturizing facto r of normai huma n sk in. In contrast to the effects of humectants (g lycero l, propylene g lycol), urea acts a moi sturi zer even in xerotic sk in cond itions. As water is the most important plastifying agent in stratum corne um, humidity significantly improves smoothness of the sk in. Atopic skin with its lac k of wa te r binding capac ity needs urea fo r its care. Keratolytic - keratinolytic action: By spli tting hydrogen bonds, urea in hig h conce ntra tions (40%) exerts a proteinolytic (keratinolyti c) activity. Th is effect may be used fo r a chem ical onychol ysis. Desquamating action: Urea loosens the intercellular conn ections between the corneocytes thus facilitating desquamat ion of superfi cial cells and, on the other hand, increasing penetrati on. This effect may activate of drugs which are applied concomitantly with urea. Antimicrobial action: By absorbing water, urea hinders the growth of microorganisms, without provok ing an antimicrobial effect in the usual se nse. T hus, p rese rvation o f urea-co ntai n ing products needs less po tenti al a ll erge ns in the form of the usual mic robistatic substances. Antiinflammatory action: The a nt iin fl a m matory action of urea consists of severa! components: antipro lifera ti ve (in states of inc reased cellula r tumover, only), a ntiedematous (topica! W Raab "diuretic" effect, as could be demonstrated in cases of lymphostatic papillomatosis cutis verrucosa), and antipruritic (inhibitory action on e nzymatic activities which promote itc h). Dermatologica/ indications tor urea Topica! pre parations containing urea may successfull y be used in a variety of dermatoses: - Atopic eczema (the rapeutic appli cation, skin care in states of dryness and various fonns of subacute and c hronic, dry eczemas. - Psoriasis vulgaris and o the r scaly diseases. - Senile skin and other states of excessive dryness and itch. - Ichthyosis - Hyperkeratoses, keratoses. - Chemical onycholysis, e.g. in onychomycoses. without changing the extent of undesi rable action s. E. g., 1% hydrocortiso ne reaches the therapeutic effectiveness of 0.025% fluocinonide when 10% urea is incorporateci. In combination with glucocorticoids, the antimicrobial action of urea is of special importance. - Anthralin: Th e a ddition of 17 % urea to anthralin 0.05 - 0.2% improves the antisporiatic action , in short contact therapy a s we ll as in day- tim e care. Irritati o n a nd s tain i ng by an thralin is dimini shed, so compliance is in creased. - Tre tinoin: In severe ichthyoses, w ith the exceptio n of th e inflammatory and e ryth rodermatic fonns, a combination of 0.03% tretinoin w ith I 0% urea may be used. Suc h a product may a lso prove to be s uccessfu l in stubborn cases of chroni c psoriasis. - Salicy lic ac id : In stubborn c ases of hype rkeratoses, a combination conta ining 10% urea and I 0% salicylic acid was recommended. Urea combined with other drugs Urea is cosmetology By its desquamating and hydrating actions, urea increases the bioavailability of other drugs. Furthermore, urea enhances the topica! activity of som e s ub s tan ces by influe n c ing t hei r sol ubili ty and crystal struc ture. Urea can be successfully combined with the fo llow ing substances: - Glucocorticoids: The add ition of urea increases the therape utic activity of the glucocorticoids In cosmetic proc}uct\ oreams, ointments or bes t - lotio ns, urea i~ incorporateci for sk in ca re purpose s in co nce ntrations between 2 a nd 5 %. For cosm e ti c purpos e s, the m o isturi z in g ac tion of urea is of g reates t impo rtance. Skin care produc ts for senescent peop le sho uld contain ure a. One may ass ume that the use of urea is cosmetic products w ill steadi ly inc rease (3). References 1. Kligman A. M.: Dermatologica! uses of urea. Acta Dermato-Venereol ., Stockholm, 37: 155159 , 1957 2. Raab W.: Harnstoff in der Dennatol ogie. Hautarzt 40, Suppi. 9, 1989 3. Raab W.: Urea in cosmetology. Cosmet. Toi/etr. 105, 97-102, 1990 4. Wohlrab W.: Zur Yerwendung von Harnstoff in der De nnatologie. Der Deutsche Dermatologe 36: 528-537, 1988 17 J. Appl. Cosmetol. 9, 19-23 (January- March 1991) CHANGES IN STRATUM CORNEUM AFTER UREA APPLICATION TO HUMAN SKIN IN VIVO. ELECTRON MICROSCOPIC INVESTIGATIONS G. StGttgen Kissinger Strabe 12, D-Berlin 33 Received: October 26, 1989. Presented at 3rd lnternational Congress on Cosmetic Dermatology "Progress in Cosmetic Dermatology" - 27 - 29th October 1989, Wien Key words: Stratum Corneum Changes: Urea and Keratin; Electron Microscopie lnvestigation - - - - - - - - - - - - - - - - - Synopsis Urea, 10% in cream or ointme nt, applied in vivo for 24 and 48 hours with part occl usion changes the inner structure of the horny cells, depending on time and the excipients. Splitting of the keratin changes the matrix and the osmiophilic behaviour, especia lly in the upper regions. After 48 hours fine granul ation within the horny cel ls and enhanceme nt of cavities can be demonstrated. There is no evide nce of any changes in the osmiophilic materiai in the intercellular spaces. Urea does not enhance permeabi lity per se, it increases the surface of the keratinous mate riai and its capacity to bind water and other substances with low molecular we ight. Riassunto L'appl icazione topica mediante bendaggio parzialmente occlusivo di una crema o di un unguento a l 10% di urea provoca modificazioni della struttura de llo strato corneo, dipendente dal tempo di contatto e dal tipo di veicolo. S i osserva del materiale c heratinico con variazioni a livello de lle matrici. Dopo 48 ore si osserva una fine granulazione delle cellule cornee con comparsa d i cavità. Non si evi denziano cambiamenti degli spazi intercellulari. L'urea non facilita di per se la permeabilità ma aumenta la superfi cie del materiale cheratinizzato e la sua capacità di legare acqua e altre sostanze a basso peso molecolare. 19 Changes in stratum corneum affer urea application to human skin in vivo lntroduction The influence of urea on the homy layer and the ensueing changes in function have been researched very carefull y (I, 2, 3, 5). The external use of urea, incorporated into different ba ses, in dermatology and cosmetology depends on such data (6) . The changes in the stru cture of th e horn y Jayer after topi ca l application of urea to human be ings have not however, unti! no w bee n examin ed electron microsco picall y, either in vivo o r in vitro. Stratum corneum can be divided into 3 layers (Orfanos 1981 ). I. Flat horny cells in the basai zone hav ing electron dense membranes which enclose the homogeneous relatively light materiai. 2. The middle zone cons ists of horn y cells with an electron - dense network of different structures which can be interrupted by small cavities. 3. Finally the superfi cial zone is characterised by broad intercellular spaces and lack of desmosomes, which are visi ble as electron dense threads onl y in - the lower horny layer . Tonofilaments and the hyaline granul es are the materiai of which the keratin, in the form of bigger tonofibril hyalin complexes is composed. The formation of horny layer is a qui ck process, mo re or less a jump, into keratinisation. Horn y cell s with an osmiophobic filaments, embedded in an osmiophilic matrix are known as a A-cells. Horny cells with a pattern of osmiophilic filamen s embedded in an osmiophilic matri x are classified as B-horny cells. T he inter ce llul ar su bstance is fo rm ed by membrane coatin g granules (Odland-bodies) which are extruded into the intercellular space in the granul ar layer and fo rm glycosphingolipids, ceramides, nonesterified sterols and fat ty acids. T his materiai fo rms th e bilipid layers which as lamellar sheets surrounding the horny cells (4). 20 Methods We took punch biopsies (2mm in diameter) after application of I 0% urea in creams or ointment for 24 hours or 48 hours and examined them by elettron microscopy. For the first 24 hours occlusive dressings were used , subseq ue ntl y the application s were lettopen. As a contro! the effect of cream or ointment without urea, was also examined. Excised skin (for the region around a skin tumour) was used for an in vivo experiment at 30°C with the same conditions as in vitro. The region used was to the right and left of the umbilical line and an area of 25 cm2 was used for the applications. The structure of the homy layer in the same area was examined prior to any applications. Basodexan cream and o intment with and witho ut I 0% urea were made available by the courtesy of Rohm Pharma. The experiment was performed on healthy probands, who gave their consent to the procedures. The punch s lices were cut with an ultratom DMU 3 (Reichardt) and examined by an electron microscope Dm 9 of Cari Zeiss. After fixati on (2% glutara ldehyde, 2% 05S04 in phosphate buffer 7.4) the slices were embedded in araldi te. Parameters of the effect of urea are: the amount of electron dense materia] in the homy cells, including the celi envelopes, and of the intercellular substance, the thickness of the cells and the width of the intercellular space. Results The composition of the homy layer structures of the skin treated with urea shows the following changes in comparison with the contro! skin: The thickness of the homy cells has diminished, especially in the region towards the epidermis. G. StUttgen The number of homy layers, usually 11 to 12, is reduced to 8 to 10. Additionally vac uoli sation , development of cavities and changes to the inner structures towards the skin surface are obvious. The density - the osmiophilic behav iour changes and this is especially obvious in the homy layer, as is the smaller diameter of the transverse cross sections. The intercellular substance and the intercellular space show no changes. The width of the intercell ular space seems in generai not to be changed. The desmosomes, separated from the tonofibril s are now part of the intercellular materiai and disappear into the upper region of the homy layer (Fig. 1,2) s 24 ...___ _ _ _ _ _ _ _ _ _ _ _ _ _ FIGURE 2 Urea ointment in vitro on human horny /ayer (x23750) 024 OH24 048 OH48 Urea ointment effect in vivo on human horny layers (x 23750) K = Biopsy before treatment 024 = 24 h affer application of ointment without urea OH24 = 24 h afferapplication of 10% urea ointment 048 = 48 h affer application of ointment without urea OH48 = 48 h affer application of 10% urea ointment = 24 h affer app/ication of ointment without urea = 24 h affer application of 10% urea ointment = 48 h affer application of ointment without urea = 48 h affer app/ication ot 10% urea ointment The swelling of the hom y cells can be combined with bulging and narrowing of the intercellular space. It is obvious that the target of th e urea is the horny cell , whi ch show evidence of loosening of the hydrogen bonds of the keratin. This phenomenon is obviously more expressed after 48 hours (occlusive dressings fo r 24 hours, followed by 24 hours open application). The envelopes remain intact, irrespective of cream, ointment or time. (Fig. 3) 21 Changes in stratum corneum after urea application to human skin in vivo 10' tower Corìum ......:._subcutaneous • fai • 30 min x 100 min 10 ' O 300min + 1000 min + ..__ __ o ~----- FA 10 ' ....:;_~---------"-"""'"'"-'-'- flGUREJ Urea cream effect in vivo on human horny layer (x 23750) C48 = 48 h after application without urea CH48 = 48 h after application of 10% urea cream 10• Discussion 10' Urea applied in vivo and in vitro shows binding to filaments of the ke ratin and the e nve lopes aro und th e keratin filaments w hich are less tightly packed, and permits accumulati on of water in its variable fonns. The inner struc ture of the horny cells has changed and shows c lear "splitting" of the horny filaments. These effects of urea, replac ing water o n the one hand and binding water on the other, and the action as a solvent on the different micro elements of the celi provide the key to a broad spectrum of effects both med icai and cos me ti c impo rtance ( 11 , 12). From the tox icological and hi stological points of view there are no objections in regard to an impai red barrier fu nction using I 0 % urea which permeates the sk in (Fig. 4). The intercellular spaces w ith the ir lipid layers and proteoglycans are adequate to inh ibit uncontrolled permeation. Steroids show an increased rate using urea. On the other hand smaller molecul es such as Imida zo les (A ntimyco tics) show an increased accumulation in the horny layer and a smaller flux towards the corium ( I 0). The effects of urea do not greatly differ betwee n 22 400 800 1200 1600 2000 2400 Depth (µm) ~--------------- FIGURE4 Permeating of urea 10% cream Examinations with chamber technique in vitro using human skin (abdomen) Application of 5 mg cream/2 erri' = 250 µ urea/erri' TA = stripped skin (8 x with Tesafilm) living skin and excised skin in vi tro . T he water uptake from the subcorneal layers to the horny layer has a lso to be taken into cons ideration. The microbial materi ai of the horny layer is a lso by urea. Th e base in which urea is inco rpo rateci is responsible for the depth of its action whic h depencl s on t he diffu s ion. Urea can not be regardecl as a genera i en hancer of permeabil ity of th e human strat um co rneum in the s ame sense as dimethylsulfoxide (DMSO) o r laurocapram (Azone) . The intercell ul a r space with its bilipid layers is only passively involved by swe lling of the horny ce lls w it hout a n y vis ible change of the e nvelope. G. StQttgen Refe rene es I. Bohm W, Braun W, Pankow B, Wohlrab W, Peker J (1974): Ùber die Reaktion der Epidermis nach Harnstoffeinwirkung. I. Epidermales Testsystem. Dermatol Wochenschr 160: 373. 2. Bohm W, Braun W, Pankow B, Wohlrab W, Peker J (1974) : Epidermisreaktion nac h Harnstoffeinwirkung. Vortr Ref Dermatol Wochenschr 160: 597. 3. Collett JH, Flood BL (1976): Some effects of urea on drug dissolution. J Pharm Pharmacol 28:206 4. Elias PM, Feingold K R, Menon G K, Grayson S, Williams M I, Grubauer G (San Francisco, Calif.) (1987): The Stratum corneum Two-Compartment Model and Its Functional Implications In: B Shroot, H. Schaefer (Ed.) Skin Pharmacokinetics, Karger. Base!, MUnchen, London, New York, Paris, New Delhi , Singapore, Tokyo, Sydney. 5. Hellgren L., Larsson K (1974): On the effect of urea on human epidermis. Dermatologica 149: 289 6. Kligman AM (1957): Dermatolgic uses of urea. Acta Derm Venereo/ (Stockh) 37: 155 7. Orfanus CE (1981): Aufbau der Hornschicht im Hinblick auf ihre Funktion. In: Klaschka F (Hrsg) Stratum corneum. Grosse, Berlin. 8. Schwartze G (1974): Zum Einfl uB von Harnstoff auf Proteine der Haut.Yortr. Ref Dermatol Wochenschr (lpz) 160:598 9. Schwartz E (1974): Freie Aminosauren und Harnstoff in psoriatischen und normalen, epidermalen Yerhornungs. produkten. Arch Klin Exp Dermato/ 225:299 10. Sttittgen G (1989): Penetration sforderung lokal appl izieter Wirkstoffe durch Harnstoff. In: Raab W (Hrsg) Harnstoff in der Dermatolig ie. Der Hauttarzt 40, suppi 9. 11. Wohlrab, W. (1984): The influence of urea on the penetration kinetics of topi cally applied corticosteroids. Acta Derm Venereo/. (Stockh. ) 64:233-238. 12. Wohlrab, W. (1988): Der E influB von Harns toff auf die Wasse r-bindungs kapaz itat d er menschlichen Homschicht. Dermato/. Monatsschr. 174:622-676. 23 BookRev1ew Series Editor: P. Morganti 2 INTERNATIONAL EDIEMME 24 Edited By : P. Morganti , F.J.G. Ebling BookReview Cosmetic Dermatology Series Editor: P. Morganti Volume 2 Every day Problems in Dermatology: The Cosmetic Connection Editors: P. Morganti, F.J.G. Ebling Every day Problems in Dermatology: The Cosmetic Connection is the second addition to the Cosmetic Dermatology Series This book is comprised of 4 1 previously unpublished papers dealing with research in various fields of cosmetic dermatology. The main themes covered are: inter-relationship between drugs and cosmetic in the skin; the efficacy of, and the raction to, cosmetics; cosmetics in sports and work; cosmetics in relation to sexuality and pregnancy; and final ly, the interconnection existing between cosmetics and diet. By so comprehensively covering the science of cosmetics, this text is indispensable to those involved in research and development for the cosmetics, toiletries and pharmaceutical industries. It will also be a great benefit to un iversity and hospital pharmacists and health care professionals entrusted with any aspect of skin care. CONTENTS (Mai n Chapters) Psycological aspects of every day cosmetic dermatology (E. Panconesi) Cosmetic, drugs and common ski n disorder (W. Raab) Percutaneous absorption and lipids of the elderly ski n (J. Wepierre) Mechanism of solar erythema (E. Quencez, P. Agache) The skin plasticisation effect of a medium chain alpha-hydroxy acid and the use of potentiators (J.C. Hill, R.J. White, M.D. Barrat, E. M ignini) Analytical problems of cosmetic evaluation resulting from EEC ltalian regulatory procedures (L. Gagliardi, A. Amato) Kathon C.G.: risk of sensitization (A.C. De Groot) Methods for evaluating irritant - erythematogenic activity in cosmetics (A. Sertoli, S. Giorgini, C. Martinelli, M.C. Melli) Social problems related to perspiration: the cosmetic connection (C. Jacobson) Barriers creams (L.C. Parish) Evaluation of a new skin barrier providing water and solvent protection (P. Morganti , S.D. Randazzo) Cosmetology and sexuality in the history of gynaecology (G. Forleo, M. Fraticelli) Metabolism of steroids in human skin (A. Lanzone, A.M. Fulghesu, F.P. Sellante, A. Caruso, S. Mancuso) The stucture and permeability of the oral mucosa (A. Jarret) Ora! mucosa and dental care problems (E. Benagian) Vitamins and minerai nutrition in the skin (B. Berra, S. Zoppi, S. Rapelli) Good manufacturing and quality contro! practices in the cosmetic industry (F. Pocchiari) Cosmetology and public health (L.Toti) 400 pages about - Hard-bound Price: U.S. $ 90.00 I in ltaly L. 120.000 25 J. Appl. Cosmetol. 9, X/X-XXIX (January- March 1991) Announcement IV INTERNATIONAL MEETING ON COSMETIC DERMATOLOGY PROGRESS IN COSMETIC DERMATOLOGY: SCIENCE AND SAFETY October 30 - November 2 , 1991 Villa MIANI - ROME - ITALY PRELIMINARY PROGRAM PROGRAMMA PRELIMINARE OCTOBER 31 th THURSDAY IGIOVEDI' 31 OTTOBRE 09.00 - Generai ro11sideratio11s I Considerazioni generali (C. Jacobson - U.S.A.) 09.30 - Ope11i11g re111arks I Note introduttive (P. Morganti - I) 09.45 - Cosmetil' prepara1io11: state o/ rhe an / I prodotti cosmetici: stato dell'arte 10.00- Sa/ety ernluatio11 o/ cosmetic i11gredie111s i11 the Europea11 Co111111u11ity a11d i11 other co11111ries I Valutazione della sicurezza degli ingredienti cosmetici nella CEE e negli altri paesi (N. Loprieno - I) 10.15 - Role o//ipids i11hiological111e111bra11es I Ruolo dei lipidi nelle membrane biologiche (B. Berra - 1) 10.30 - Adrauces i11 perrnraueous abso1p1io11 / L'assorbimento percutaneo secondo le più recenti acquisizioni (W. Shalla - D) 10.45 - Liposomes:/uture prospet'IS aud alrematire so/111io11s / I liposomi:prospettive future e soluzioni alternative (G.Gregoriades- U.K) 11 .00 - Break 11 .15 - Pediarric cosmerology: curre111 mrd future 1re11ds I La cosmesi della prima età: oggi e domani (C. Jacobson - U.S.A.) 11.30 - Sodai role cft'osmerics i11 elder/ypeo11le /Ruolosocialeckicc:;;nY:tici rella terza età (A. Tosti -1) 11.45 - Cosmeric dermarology aud 111ul'ous me111bra11es I Cosmesi dermatologica e mucose (S. Mancuso - I) 12.00 - EEC cosmetic i11g1rdie111s aut/ laheliug I L'etichettatura &!gli ingredienti cosmetici (De Giuli -1) 12.1 5 - Quality co111ro/ to protect EEC co11su111er /Il controllo qualità a difesa del consumatore (L. Gagliardi - 1) 13.00 - Bmuch SKIN SURFACE AND PERMEATION I CUTE E ASSORBIMENTO 14.00 - Liposomes as 11atural-like me111bra11es / I liposomi quali membrane naturali simili 14.15 - Liposomes as ropic carriers: progress workiug / I liposomi come carrier per uso topico: prospettive e realtà (G. Gregoriades - U.K.) 14.30 - F1111crio11 aud srability o/ liposomes as cosmeril' 1·ehicles I Funzione e stabilità dei liposomi come veicoli cosmetici (E. Menegatti - I) 14.45 - New biodegradable aut/ biocompatible wpsules /or rhe cosmetic indusry: rhe collaspheres I Le nuove capsule biodegradabili e biocompatibili per l'industria cosmetica: le collasphere (A.Huc- F) 15.00 - Discussio11 / Discussione 15.30 - The choice o/ rehicles i11 cosmeric dermarology I L'importanza dei veicoli nella dermatologia cosmetologica (B. James - U.S.A.) 15.45 - Activity o/ l'ehicles aud di/f11sio111hro11gh the homy layer I Attività dei veicoli e loro diffusione attraverso lo strato corneo (W. Shalla - D) 16.00 - Skin permeability i11 i11/a111s aud yormg childreu / Permeabilità cutanea nella prima infanzia e nella pubertà (C. Jacobson - U.S.A.) 16.15 - Skin pemieability in elderly people I La ~rrneabilità cutanea neU'anziano (F. Kerckl Vegas - YV) 16.30- Permeabiliry o/ buccal 11111cosa 111e111bra11es I La permeabilità della mucosa orale (A. Jarret - U.K.) 16.45 - Permeabiliry o/ l'agiual mucosa s111faces I Permeabilità ed assorbimento della membrana vaginale (S. Mancuso - I) 17.00 - Discussiou / Discussione 17. 15 - Break IV INTERNATIONAL MEETING ON COSMETIC DERMATOLOGY PROGRESS IN COSMETIC DERMATOLOGY: SCIENCE AND SAFETY October 30 - November 2, 1991 - Villa MIANI - ROME - ITALY MODULO DI PRENOTAZIONE ALBERGHIERA Il presente modulo, con il deposito richiesto, dovrà essere inviato al più presto a: GIBI Studio Congressi - Via Marco Besso, 40 - 00191 ROMA -Tel. (06) 3273291 - 3286478 - Fax 3276288 (prego compilare a macchina o in siampatello) Cognome ........................................................ Nome ........................ ...... ........... ..... . Indirizzo ...... ..................................... . ............................................................ ...... . c.a.p...................... Cit1à ...... .... ..... ... ....................... .. Tel. ... .......... .... .......... ... ........ .. .. . Condizioni: - I prezzi si intendono per camera, per notte e includono la prima colazione o la mezza pensione - Tutte le camere hanno servizi privati - La richiesta di prenotazione dovrà pervenire il più presto possibile e dovrà essere accompagnata da un deposito pari al costo della prima notte più Lit. 15.000 a camera per spese di prenotazione - Per eventuali cancellazioni che perverranno entro il 27 giugno '9 1 saranno addebitate le sole spese di prenotazione, dopo tale data sarà addebitata anche la prima notte Camera e piccola colazione O Hotel Hilton (l' cat. lusso) O camera singola Mezza pensione O camera doppia O camera doppia uso singola o o o 260.000 342.000 301.000 o o o 329.000 480.000 370.000 O Hotel Clodio (2' cat.) O camera doppia O camera doppia uso singola o o 220.000 179.000 o o 290.000 214.000 O Hotel Olympic (2' cat.) O camera singola O camera doppia o o 170.000 210.000 Vi richiedo di prenotare n. .... camera(e) su specificata( e) con arrivo il giorno .. .. ..... .. ...... ..... ....... .. . e partenza il giorno ........... . Allego il deposito della prima notte più Lit. 15.000 a camera a mezzo assegno n......................... ...... della banca ................... . per un importo di Lit. .. ....... ............... . N.B. - Le camere singole sono in numero limitato e potranno essere assegnate solo alle prime prenotazioni. Note .... ............... ...................................................................................... . Data ... ... ........ .... ......... .... .... Firma ............................................................... . IV INTERNATIONAL MEETING ON COSMETIC DERMATOLOGY PROGRESS IN COSMETIC DERMATOLOGY: SCIENCE AND SAFETY October 30 - November 2, 1991 - Villa MIANI- ROME - ITALY HOTEL RESERVATION FORM Please type or print using block letters and retum to: GIBI Studio Congressi - Via Marco Besso, 40 - 00191 ROMA -Te!. (06) 3273291 - 3286478 - Fax 3276288 Sumame ......... ... ..... .... ........... ..... ....... ....... ..... . Name . .. .. ........... ......... .. ..... ... . ..... ...... . Address . ............. ..... .... ...................... ..... .. .. .... Country ......... . ........ . ...... .. ........ .. .. ..... . Zip code . .... . ....... ... . City ..... . .... ............... .. .. . ... .. ......... Tel.No ...... ...... ... ...... ... .... .. . .. ..... . . Conditions: - Prices are per room, per night and include bed and breackfast or half board service - This reservation form should reach GIBI Studio Congressi as soon as possible - First night deposit plus Lit. 15.000 as agency fee are required at the moment of reservation The deposi! will be deducted from the hotel bili upon departure - Request for cancellations must be received before July 27, 199 I. For cancellations received before July 27 only the agency fee will be charged. After this date also the first night deposit will be charged Bed and breakfast Half board O Hotel Hilton (I ' cat. Luxory) O single room O double room O double room for single use o o o 260.000 342.000 301.000 o o o 329.000 480.000 370.000 O Hotel Clodio (2' cat.) O double room O double room for single use o o 220.000 179.000 o o 290.000 214.000 O Hotel Olympic (2' cat.) O single room O double room o o 170.000 210.000 Please reserve n... .. ........ .. room(s) arrivai date ..................... departure date ................... .. . . I enclose first night deposit plus Lit. 15.000 per room with check n.............. Bank.......... . ... ..... ..... . of Lit. ... .. .......... ... ...... .. ......... ... ....... ... ..... ...... .. ......... ... ........ .. ...... .. ... ..... .... . N.B. - As single rooms are very few they will be assigned on first come, first served basis. Note ................................... ...... .. .. ........ ....... .......... ....................... ....... ..... . Date .... . ... ... ...... .. ....... .... .... . Signature...... ..... .. ... .... .. . .. ........ .... .. ............... .. .... . IV INTERNATIONAL MEETING ON COSMETIC DERMATOLOGY PROGRESS IN COSMETIC DERMATOLOGY: SCIENCE AND SAFETY October 30 · November 2 , 1991 · Villa MIANI · ROME · ITALY SCHEDA DI ISCRIZIONE Cognome . ......... ...... . .. .............................. . ...... Nome .. ..... .. ... .................... ... ... ...... .. . Indirizzo .. ..... ...... .... ........ ..... . ...... .......... .......... .. . ... ............. ....................... ........... . (dell'intestatario della fattura) c.a.p ........ ... .... .... ............... . .. .. Città .... ..... ....... .... .............. ....... . .. ...... . .... ..... ..... ... . . . Telefono ......... .... .... . ..... ........ ...... .................... C.F. • P. IVA ...... ... ........ ... .......... . .. .. .. ... . (dell'intestatario della fattura) Quota di iscrizione: entro il 15 luglio Lit. 650.000 dopo il 15 luglio Lit. 850.000 La scheda con allegato assegno o vaglia postale intestato a GIBI Studio Congressi, dovranno essere inviati alla Segreteria Organizzativa: GIBI Studio Congressi · Via Marco Besso, 40 · 00191 ROMA· Tel. (06) 3273291· 3286478 ·Fax 3276288 Allegato assegno/vaglia n.. ..... ............... .................. ..... della Banca . .... ...... .. ..... .. ....... ........ ... . di Lit. ......... ............. .. ................. ... ................ ..... .............. ..... ............... ................ . Data ... .. ...... ... ............. . ..... . ..... Firma ... .. .. ....... ...... .. ........ ....... ............. . .. . .. .. .. .. ... ... . .. . IVINTERNATIONALMEETING ON COSMETIC DERMATOLOGY PROGRESS IN COSMETIC DERMATOLOGY: SCIENCE AND SAFETY October 30 · November 2, 199 1·Villa MIANI · ROME · ITALY REGISTRATION FORM Surname ......... ..... ........ . .. ......... ......... .... ... .. ..... Name ..... . .. . ...... .. ....... ....... .............. .. . Address .... .... .. ..... .......................... ... ...... .... ... .......... ........ ........ ...... .... .... ... ...... . ... . . Zip Code .................................. City..................... .... .. ............ ......... .. ....... .. ............ . Country ........ . ..... ... . .. . ..... .... ....... . .. ...... . ..... ..................... ... ....................... .. . ... ...... . Telephone No . ....... .......... ................ ... ...... ............. . ........ ... .... ... .... ... ..... ... ... ..... .. ..... . Registration fee: beforeJuly 15 Lit. 650.000 after July 15 Lit. 850.000 This form, duly filled in and signed, with check at the order of GIBI Studio Congressi, must be sent to the Organizating Secretariat: GIBI Studio Congressi· Via Marco Besso, 40 · 00191 ROMA · Tel. (06) 3273291· 3286478 ·Fax 3276288 I enclose check n........ .. ..... .................... .............. ..... Bank ........... .... .............................. . of ltalian Lire........... ...... ........... ......... ...... . ...... ....... ............. . .... ..... .... ....... ....... .......... . Date ..... ... ....... .. . ..... ...... .......... Signature .... . ...... .. ....... ... ..................... ..... .. ...... . .. ...... . . PROGRESS IN COSMETIC DERMATOLOGY: SCIENCE AND SAFETY Riassunto (solo in lingua Inglese) Abstract Reproduction Form (English language only) Trascrivere il riassunto nel rettangolo I Type abstract wilhin the rectangle. Per ulteriori infonnazioni leggere le indicazioni sul re1ro I Forf11r1/ier i11for111111io11 see directio11s 011 11ex1 page Titolo Tille Autore Author Riassunto Abstract _ Indicazioni I Directions T itolo del lavoro - con lettere maiuscole. Tille of paper - in capitai lellers. Nome degli autori - in maiuscolo e m inuscolo, con il nom e de l relatore sotto lineato. Name of author(s) - in upper and lower case. with name ofp resenter underlined. Nome del d ipartimento I ospedale I organizzazione I città - in maiuscolo e minuscolo. Name of department I hospital I orga11isation I town I counrry - in upper and lower case. Interi inea 2. Leave one fine space. Util izza una macchina da scrivere elettronica. Use an electric typewriter with plastic black ribbon only. li testo apparirà sul libro degli abstract come verrà inviato e gli eventual i errori ri marrnnno visibil i. Your text will appear in rhe book of abstrac/ exactly as you send il and every errar or impe1fection will be visible. Ultima data di ricevimento per il riassunto: 15 Luglio 1991 Deadline for receipt of abstract: July 15,1991 Rispedire il riassunto a: I Please return the abstract to: P. Morganti, Via innocenza Xl, 41 - 00165 Roma (ltaly) NAME OF PRESENTER I NOME DEL RELATORE Nome/ Name - - - - - -- - - - - - -- - - - - - - - -- -- - -- -- -- Ospedale I Hospital - Organizzazione I Organisation - -- - -- - - - -- - -- - - - - - - Indirizzo I Address - - - - - -- -- - - - -- - - - - - - - - - - - - -- - -- Città I Town - -- -- - - -- -- - - - - - - -- - Nazione I Country I I Telefono I Teleplwne _ _____ _ _ _ _ _ Telex _ _ _ _ Telefax - - - - - - -- - ~ I Announcement 18TH WORLD CONGRESS OF DERMATOLOGY Scholarships Available for the 18th World Congress of Dermatology The 18th World Congress of Derrnatology wi ll take piace in New York City from June 12- 18, 1992. In an effort to encou rage the partic ipation of you ng derrnatologists, the Congress wi ll award a limited number of scholarships, as follows: Dermatolo~ists from Developin~ Countries: Appl icants must be no older than 38 years of age at the time of the Congress. The scholarship will provide complimentary registration and hotel accommodations (two awardees to a room), and a moderate subsistence allowance. Awards are competiti ve andare contingent on sponsorship by one's national society. Abstract submission is mandatory. Obtain further information and appl ication forms from your national society before June I , 1991 . Dermatolo~ists from Developed Countries: Applicant must be a Resident or Fe llow in a full -time training program. The Scholarship will provide complimentary registration and a small subsistence allowance. A letter from the educational or training institution va lidating the applicant's status must be submitted with the appl ication fonn. Abstract submission is mandatory. Forrns are available from the 18th World Congress Secretariat, 875 Kings Highway, W. Deptford, NJ 08096, USA. Cali for Abstracts for the 18th World Congress of Dermatology The l 8th World Congress of Dermatology Organizing Committee and the International League of Dermatological Societies inv ite the submiss ion of abstracts for short communications to be presented at the I 8th World Congress, June 12-1 8, 1992, New York City. Selected abstracts will be presented in the following sessions: - Case Presentations - Four-mi nute presentations of clinica! cases of exceptional scientific and/or educational interest. - Contributions to Clinica) and Experimental Dermatolo~y Q.rfil presentations of originai contributions of clinical, therapeutic or laboratory investigations. Poster presentations of originai contributions to cl inical and laboratory investigation which can be effectively di splayed by illustrative materiai (graphs, charts and tables). Authors are to be present during specified times for discussion of the posted materia!. Abstracts must be submitted on the officiai Congress Abstract Reproduction Form and received before August 1, 1991. Forrns and submission guidelines are avai lable from the 18th World Congress Secretariat, 875 Kings Highway, W. Deptford, NJ 08096, USA. Chiuso in Tipografia: 15 Luglio 1991 Joumal of Applied Cosmetology published quarterly by INTERNATIONAL EDIEMME, Via Innocenzo XI, 41, 00165 Roma Italy. Direttore responsabile P. Morganti. Direzione, Redazione ed Amministrazione Via Innocenzo Xl, 00165 Roma Italy. Coordinamento all ' edizione P. Arcuri. Stampa Edigrafica Aldina s.r.l., Via della Massimilla 50, Roma, te!. 6692801-6693099. Progetto grafico ed impaginazione STYLOgrafica Roma. Spedizione in abbonamento postale gruppo IV(70. Aut. del Trib. di Roma n. 3173/83 dell' 8-7-83. MAVIGEN IDRO SCHIUMA MAVIGEN IDROSCHIUMA trova la sua specifica prescrizione sopratutto per le pelli grasse ed acneiche che dopo i trattamenti farmacologici con benzoi! perossido, acido retinoico, antibiotici o acido azelaico hanno bisogno, in genere, di essere reidratate. lt'k1 mav1 La ricerca scientifica nella dermocosmesi Mavi Sud S.r.l. - Viale dell'Industria, 1 - 04011 Aprilia (LT) La giusta soluzione L}jfJ. l11éM La le rea sci ntlf1ca nell J m cos.mesi Mavi Sud S.r.l. - Viale dell'Industria, 1 - 04011 Aprilia (L T)