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
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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.
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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
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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. If a materials is
not listed, then the trademarked name can be used, with the chemical composition g iven in footnotes.
INFORMAZIONI PER L'ABBONAMENTO
L'abbonamento annuale comprende quattro numeri. È possibile ottenere abbonamenti a prezzo
ridotto da parte dei ricercatori che lavorano presso Istituti che abbiano sottoscritto almeno un
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essere effettuate mediante assegni postali, bancari, di conto corrente o per contanti indirizzandoli a:
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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
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PROGRESS IN COSMETIC DERMATOLOGY: SCIENCE AND SAFETY
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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
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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)

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