I AMMONIO LATTATO "ATTIVATO" LA RISPOSTA DERMATOLOGICA ALLE IPERCHERATOSI Ipercheratosi intrinseca Ipercheratosi estrinseca "ACTIVATED" AMMONIUM LACTATE THE RIGHT REPLY TO HYPERKERATOSIS Emulsione - Ammonio Lattato 14% Emulsione - Ammonio Lattato 8% Ammonio Lattato 7% i Oli i lineari e ramificati - Ammonio Lattato 5% \Wcw n u localmente 2 volte al dì. A NEW MAVICEUT/CAl® Dermatologically tested 123 • Effective for initial .and maintenance therapy ( • • l • Compatible with all the drugs and cosmetics • Formulated to treat mild-to-moderate inflammatory acne, indispensable for patients with sensitive skin CLINICAL RESULTS< 1 •2 •3 , ACTIVITY CARRIED OUT BY KERATOTAL ACNE ON THE LINOLEIC ACID ANO SQUALANE CONTENTS OF SURFACE LIPIDS IN SUBJECTS AFFECTED BY ACNE JUVENILIS REDUCTION OF SURFACE LIPIDS DURING THE TREATMENT WITH KERATOTAL ACNE go..-- n=30 -n·_ lO_ _ _ P_ <0_ 005 _Wl _il*lg ~uMeoted------ 4,0 3,5 z 60+--- - -- - - - ~ 3,0 0 t so+ - - - - - - - fil 0:: 40+ - - - - - => ~ !Z 2,5 2,0 ~ 1,5 z ';!! 30+--->--- 8 1,0 20 ..,. 0,5 10 6 10 15 20 giorni Ilii Untreated lii Treated 25 l => Decreases the Squalene content of 10 settimane 30 => lliil Squalene • Llnoleic Acid 12 l Reduces excess lipids acne affected skin EFAITG z o 90+------------------~ ~ 85 ~ 80+-------------~ J: z 75+-------+-------~ ~ 70+--------#-------~ :;:: 0,5 WEEK1 => Significantly reduces EFAITG ratio ::> WEEK2 lncreases skin hydration by 97% Please see a brief summary of prescribing information on next page ~ BRIEF SUMMARY KfRATOJ'ALACNE . THE GENTLE ANTIACNE TREATMENT WITH NO-DRUG CONTENT DESCRIPTION Keratotal Acne is a special fat-free lamellar phosphatidylcholine emulsion developed for the treatment of acne. lt is delivered in a special phospholipidic-vehicle linoleic acid rich which contains glicolic acid and salicilic acid partially neutralized by a special patented blend of aminoacids INDICATIONS Keratotal Acne is indicated for the treatment of acne. Absolutely necessary as a cosmetic substitute or support in presummer and summer periods, when treatment with conventional keratolitic agents (benzoil peroxide, retinoic acid, ecc.) is not recommended. Penetrates pores to eliminate excess sebum, most acne blemishes, acne pimples, blackheads and whiteheads in a short period treatment. lts continously use helps to prevent the development of new acne efflorescences For more information cali to: Mavi Sud Sri V.le dell'Industria 1 04011 Aprilia (LI) ltaly Tel.+39.6.92.86.261 Fax +39.6.92.81.523 E-Mail:[email protected] URL=http://www.colosseum.it/st81/mavi ADVERSE REACTIONS In the first days of application transient effect such as stinging or itching may be observed HOWTOUSE Twice a day. Before applications cleanse the skin thoroughly; if stinging occurs, reduce application to once a day for the first ten days of treatment REFERENCES: 1,2 - Data on file Mavi Sud - M. Ghiczy, H.P. Nissen, H. Biltz (1996) The treatment of Acne Vulgaris by phosphatidilcholine from Soybeans, with a high conteni of linoleic acid. J. Appl. Cosmetol. 14, 137-145 3 A NEW MAVICEUTICAL® Lip protective with Glycoaminoacids<*> INDICATIONS Cosmetic adjuvant in all the forms of cheilitis and lips dryness caused by: Such as • Retinoids • • • Cheilitis or chapped lips • UV rays • • • Actinic cheilitis (acute and chronic) • Wind • • • Allergie cheilitis • Weather • • • ,Exfoliative cheilitis • Environmental pollutants • • • Angular cheilitis HOW TO USE Use day and night as a regular lipstick (*) partially neutralized by a special patented blend of aminoacids Please see a brief summary of prescribing information on next page ~ BRIEF SUMMARY KERATOTAlLABBRAM DESCRIPTION Lip protective with Glycoaminoacids<·> IN ALL THE DISORDERS OF THE MUCOCUTANEOUS INTEGUMENT OF THE LIPS Keratotal Labbra is a fasta c ti n g, uncoloured treatment to protect the lips from premature ageing and skin cancer due to UV rays. lt helps to keeps the lips very moist and well protected from the dryness caused by UV, wind, weather and environment. INDICATIONS In ali forms of dryness caused by the use of retinoids or other drugs, or by environmental pollutants. To avoid the premature lips ageing caused by UV activity. ADVERSE REACTIONS No adverse reactions to the use of this product are known. For more information cali to: Mavì Sud Sri V.le dell'Industria 104011 Aprilia (Lt) ltaly Tel. +39.6.92.86.261 Fax +39.6.92.81.523 E-Mail:[email protected] URL=http://www.colosseum.it/st81/mavi (•)partially neutralized by a special patented blend of aminoacids HOWTOUSE Apply as a regular lipstick. Keratotal Labbra is intended for round-the-clock use. PUfOLIC® Integratore dietetico di acido folico, magnesio e di acidi grassi polinsaturi 0)-6 ed 20capsu/e ro-a PUFOLIC® BRIEF SUMMARY Dietary supplement with Folic Acicl, Magnesium ancl Polyunsaturatecl Fatty Acicls omega-6 ancl omega-3 what? Dietary supplement with Folic Acid, Magnesium and Polyunsaturated Fatty Acids omega-6 and omega-3, which have a high content of DHA (docohexaenoic acid). when? Fundamental for an optium development of the brain and retinai structures in the fetus. where? • Activates synapsis and promotes neuron growth; • controls erythropoiesis; • optimizes membrane formation by protecting the internal structures of cells; • acts within the synthesis of proteins, particularly keratins, thanks to its optimum, balanced content of folic acid, magnesium, omega-6 and omega-3 (DHA) in 1:4 ratio. why? Before, during and after pregnancy, to prevent deficiencies due to poor intake, absorption and use of FOLIC ACID, OMEGA-6, OMEGA-3 and MAGNESIUM and to reduce the risk of • functional neurologie disorders in the fetus; • • • • • How to use tn7. mav1 THE EVOLUTION IN COSMETIC SCIENCE spina bifida; gestational hypertension; uterine hypercontractility; skin diseases (psoriasis, atopic eczema, alopecia, etc.); imbalances among HDL, LDL, VLDL and cholesterol that may be caused by a deficiency in the above essential nutrients. 1 to 2 capsules daily, according to a physician's directions. For more information cali to: Mavi Sud Sri - Viale dell'Industria, 1 Aprilia (LT} ltaly Te/. +39.6. 92.86.261 - Fax +39.6. 92.81.523 E-Mail:[email protected] URL:http://www.cofosseum.it/stB 1/ mavi Trimestrale di Dermatologia Cosmetologica Quarterly Review of Cosmetic Dermatology EDITOR P.MORGANTI PhD. SECRETARY GENERAL INTERNATIONAL SOCIETY of COSMETIC DERMATOLOGY Via Innocenzo Xl, 41 - 00165 Roma ( haly) • Fax +39-6-63.80.839 ASSOCIATE EDITOR S.D. RANDAZZO M.D. Profcs.<;or of DERMATOLOGY UNIVERSITY OF CATANIA Via lacona, 7 • 95124 Ca1ania (h aly) ·Fax +39-95-7159894 ASSISTANT EDITOR M.B.JAMES M.D. PROGRAM DIRECTOR INTERNATIONAL SOCIETY of COSMETIC DERMATOLOGY JAMES CLINIC Sui1c 1076 Tanncry Lane Camdcn. Maine 04843 USA· Fax 001-407-9972137 SECRETARY EDITOR M. PASCOLI Via Innocenzo Xl, 41 · 00165 Roma (haly) ·Fax +39-6-92.81.523 EDITO RI AL AOVISORY BOARO P. AGACHE G. BELLOMONTE W.F. BERGFELD B. BERRA R.CAPUTO O. CAR LES IMO D. CERIMELE E. CHIACCHIERINI I .COTTE M.A. DINA G. FAB RIZ I J.A. GRAHAM L. GAGLIARDI B. GUARNERI AJ. JOUHAR F.H. KEMPER A.M. KLIGMAN N. LOPRIENO S. MADDIN G. PUGLISI C.L. MENEG HI NI N. ORENTREICH E. PANCONESI R. PAOLETTI W.E. PAR ISH L. PUGLISI W. RAAB G. RABB IOSI A. REBORA V. RIZZA G. SALVATORE A.SANNA P. SANTOIANN I H. SCHAEFER A. SERTOLI A.STAMMATI H. TRONNIER V. VA LKOVIC MD. Prof. of Dcm1a1. Ccni rc Hosp. Rcgional dc Bcsançon (F) CChcm, Prof. ofChcm., Food Dcpan ISI. Sup. Sani1à • Romc ( I) MD. FACP Cleveland Cl inie Ohio (USA) DSc. Prof. of Biol. Chcm. Un iv. of Mi lano (I) MD. Prof. and Chainnan. Dcpan of Dcnn:ll. Univ. of Milano ( I) MD, Prof.. Dcpan. of Dcnn:ll. Univ. of Romc (I) MD, Pror. and Chainmm. Depart . of Dcm1at. Catholic Univ. of Romc (I) CChcm. Prof. and Chainnan. Dcpan. Tcchn. of Commcrcc Univ. of Romc (I) DSc, Prof. of Cosmc1. IPIL Lyon (F) MD. Prof. and Chainnan. Dcpart. of Phruol. Anal. Catholic Univ. of Romc (I) MD. Ass. Prof. of Paedria1ic Dcm1a1ologiS1, Ca1hol ic Univ. of Rome (I) B.Sc, PhD. Dcp1. Dcrma1ology Un iv. of Pennsylvania (USA) D.Ch. Dcpan. of Pharm. Chcm. ls1. Sup. Sani1à of Rome ( I) MD, Prof. and Chairman. Dcpan. of Derma!. Univ. of Messina (I) M.B.MRSC Beacoosfield (GB) MD. Emeri1us Prof.. Pharmacology & Toxicology. Univ. MunSlcr (D) MD, PhD, Prof. of Dcrmalol. Univ. of Pennsylvania Philadclphia (USA) DSc, Prof. of Gene1ica Univ. of Pisa (I) MD. ERCP Clin. Prof. Dcrma1ol. Div. Dcrmai. Univ. BR. Columbia, Vancouver (C) CChem. Dcpan. of Phannacol. and Tox. Univ. of Catania ( I) MD. Prof. and Chairman, Dcp>n. of Derma!. Univ. of Bari ( I) MD. Clin. Prof. of Dem1a1. New York (USA) MD. Prof. and Chainnan, Dcpan. of Derma!. Univ. of Firenze (I) MD. Prof. and Chainnan. Dcpart. of Phannacol. and Tox. Univ. of Milano (I) MA, PhD. BVSc. Hcad of Environmcn1al Safe1y Division. Unilcvcr Research Schan brook (GB ) DSc. Prof. of Pharmacognosy Univ. of Milano (I) MD, Prof. and Chaim1an, Dcpan. of Derma!. Univ. of Wien (A) MD. Prof. and Chairman. Dcpart. of Dcm1a1. Univ. of Pavia (I) MD, Prof. and Chairman. Depan. of Derma!. Un iv. of Genova (I) PhD. Prof. of Biol. Chcm. Univ. of Ca1ania (I) CChcm. Dcpan. ofToxicol. lsl. Sup. Sani1à of Rome (I) MD, Prof. and Chainnan. Dcpan. of Microbio!. Catholic Univ. of Rome (I) MD, Prof. and Chainnan. Depan. of Dcnna1. Uni v. of Napoli (I) Ph.D., Prof. and Scicn1ific Oircclor L'Oreal, Paris (F') MD. Assoc. Prof. of Allergie and Occupa1ional Dcm1a1. Univ. of Firenze (I) DSC, Dcpan. ofToxicol. lns1. Sup. Sani1à of Rome (I) MD. Emcri1us Prof.. Derma1ology.. Univ. Wiuen-Herdccke (D) Ph.D. Prof. of Physic Rudcr Boskovic lnsl. of Zagrcb (CRO) 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 sk in and on cosmetics. It is aimed at cosmetic chemists, dermatologists, microbiologists, pharmacists, experimental biologists, toxicologists, plastic surgeons, and ali other scientists· working on products which will come into con.taci 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 respective contributors and are nor 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 subm itted for publication elsewhere. By submitting a manuscript, the authors agree that the copyright for their articles is transferred to the publisher if and when the article is accepted for publication. None of the conteni 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 will be features 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 Artic/es: 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. Slzort Communications: the lenght should not exceed S 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 a1ticles 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 INTERNATJONAL EDIEMME Via Innocenzo Xl, 41 00165 Rome - Italy Te!. 0039/6/393.78.788 Fnx. 0039/6/63.80.839 INFORMATION FOR AUTHORS Papers must be submitted in Eng lish. Authors whose mother tongue is not English should arrange for the ir manuscripts to be written in proper English prior to submission. Procedure of Submissio11 of Manu scripts: submit three cop ies of both the manuscript and all illustrati ve materiai to the above address. Orga11izatio11 of the Ma11uscript: investigati ve studies s hould be organi zed as follo w: title, abstract page, introducti on, materi ai and method s, results, d iscussion. acknowledg ments, references, legend for figures, tables. All pages should be numered consecuti vely starting with the abstract. The entire manuscript is to be typewritten, d ouble-spaced, and with 3 cm margins. Tracie names must be capitalized: the common name for compounds may be used if the formai chemical name as established by international convention is g iven after the first use. Any abbrev iations other than those which are generall y accepted must be d efined. In the text, references to dual authors will use both surnames throug hout. For mul tiple authors, use the surnames o f al! authors at the fi rst refcrence and onl y the first author fol lowed by "et al." thereafter. Please mark in the marg in o f the manuscri pt the desired position o f the fi g ures and tables. To allow faster publication only set of proo fs will be furni sched to the author including the fi gures and tables in their final positio n. Title page: list the title, name(s) and degree(s) of author(s). department(s) and institution(s) at which the work was done, city, state, and postai code. Any preliminary report or abstract of the work should be re ferred to as a footnote to the title. Summary: each paper must be headed by an English lang uage title of not aver 70 c haracters (including spaces) suitable far use as a running head and must also be proceded by an Eng lish summary not exceeding 300 words ty ped double-spaced. The summary wi ll include statements of the problem, method of study, results, and conc lusions. S ince this summary w ill be used by astracting journals, it must be self- explanatory aild should not inlcude abbreviations, footnot es, and references. Foot11otes: should be li sted consecutively at the bottom of the page on which they fall , designateci by the fo llowing symbo ls in a rder *,+,+,§. II,**, etc. Key Words: key words far computerised s torage and retrieval of in fo rmatio n should be incorporated in the summary. Refere11ces: the references have to be abbreviateci as listed in the lndex Medicus. The style of the references must conform to thc examples given below: I) Robbins CR, Ke llych ( 1970) A mi noacid composition of human hair. Text Res J 40:89 1-896 2) Strehler BL ( 1977) Time, cells and agi ng 2nd edn. Academic Press, New York 3) Ebling FJ. Rook ( 1972) Ciclic acti vity of the fo llicle. In : Textbook of dermatology 11 , Blackwell , Oxford, p. 1567-1 573. Illustratio11s: fig ures should be numbered co nsecutively using Arabic numerals Tables should be numbered consecut ively, using Roman numerals. Ali photographs should be black and white, g lossy and unmounted. The number and size of illustration s hould be restricted to the minimum needed to clari fy the text. Authors requi ring extra space far illustrations w ill be charge accordingly. This is also the case for color illustrations. All fi gures, photographs, graphs, or diagrams s hould be submitted on separate sheets . A nimai Experiments: descriptions o f animai experi ments should include full d etails of the types of animai used (inbred, etc.) and the conditions under which they were kept (standard diet , etc .) Trade Names: all common cosmetic ing red ients should be re ferred to by the ir generic names, as indicatcd in the latesr editi on of CTFA Cos metic Ing redienr Dicti onary, and the European Pharrnacopeia. Ifa material s i ~ not li sted , then the trademarked name can be used, with the chemical composition given 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 abbonamento a prezzo normale. L'Editore potrà fornire a richiesta notizie più dettagliate. Le sottoscrizioni di abbonamento possono essere effettuate mediante assegni postali, bancari, di conto corrente o per contanti indirizzandoli a: INTERNATIONAL EDIEMME - Via Innocenzo XI, 41, 00165 ROMA - ITALIA c/c bancario n. 3184/51 Banca di Roma Ag. 1- Aprilia (LT) - ITALIA L'IVA è a carico dell'editore, non detraibile dall'abbonato a norma art. 74 lett. 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The Editor(s) and publisher, disclaim 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 Cosmetic Dermatology INFORMAZIONI PER L'ABBONAMENTO L'abbonamento annuale comprende quattro numeri. ~possibi le ottenere abbonamenli •t prezzo ridotto da parte dci riccrca1ori che lavorano presso Istituti che abbiano sotto.serino almeno un abOOnamcnto a prezzo nonnale. L'Edi tore po1ra fornire a richiesta notizie più dettagliate. Le sottoscrizioni di abbonamento possono essere cffclluatc mediante assegni postali. bancari. di conto corrente o per contanti indirizzandoli a: INTERNATIONAL EDIEMME - Via Innocenzo Xl. 41- 00165 Roma c/c bancario n. 3184/51 Banca di Roma Ag. I - Aprilia (LT) - Italia Abbonamento JOURNAL OF APPLIED COSMETOLOGY Italia L. 140.000 - Altre Nazioni $ 80 /stmzioni per/' abbonato: O desidero abbonarmi a questa ril•ista per l'anno in corso O rinnovo automaticamente il mio abboname1110 per gli anni f w uri (questa forma di abboname1110 può essere comunque disdeua in ogni 111ome1110). O desidero ricevere le norme editoriali per eventuali collabora:ioni (Scrivere in sramparello) Nome Indirizzo~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ C i t t à - - - - - - -- - - - - - - -- - - CAP - - - - - - - - - - Nazione Quarterly Review of Cosmetic Dermatology SUBSCRIPTION INFORMATION Subscriptions are cntcred on a calendar ycar basis only and include four rcgular quancrly issucs. Half-pricc subscriptions are availablc 10 rcscarch scicn1 is1 whosc institution.!t alrcady subsribc al tull rate. De1ails on applica1ion from publishcr. Paymcnt must be made in U.S. dollars using bank draft intcmational fX>Slal moncy ordcr only. l lalian rcsidcnls only may pay by pcrsonal check: dc bancario n. 3184/51 Banca di Roma Ag. I · Aprilia (LT) - llaly Order Form JOURNAL OF APPLIED COSMETOLOGY Annua/ subscription raie: Italy, Lit. 140.000 • Olher Countries $SO Additional Air Mail postage r aie: Africa and Middle East USS 12. North, Centrai and South America USS 14, Far East USS 15, Oceania USS 19,50 Please Check O I Year s11bscriptio11 O Renew my s11bscriptio11 amomatically i11f11111re years (this co11ti111iatio11 arder is instended[or subscriber's co11re11ie11ce 011/y a11d my be ca11cel/ed at a11y time). O Send me a copy ofi11formatio11for Amhors. O Please charge rhis arder 10 my credit card (Ali arder subjer ro credit approl'O/). Delete as neccssary: O AMERICAN EXPRESS O DINERS CLUB - Card Number Expiration date ............................................................. . (Please Pri111) Name Addres City - - - - - - - - - - - - - - - Postal C o d e - - - - - - - - - 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) Trimestrale di Dermatologia Cosmetologica Quarterly Review of Cosmetic Dermatology Contents Generai Articles 115 125 Biologica! functions and therapeutic properties of urea. W. Raab Practical treatment of dry skin. W. Raab Originai Laboratory Studies 133 A comparative double - blind within subject study of the efficacy and tolerability of two different derivatives of Vitamin A on skin thickness and elasticity: retinoic acid and conjugated retinyl palmitate. 139 147 E. Thom A new cosmeceutical tor the "orange peel" skin. P. Morganti. S.D. Randazzo. G.Fabrizi, C. Bruno Enhancing the glycolic acid efficacy by piezoelectric vibrations. P. Morganti, S.D. Randazzo, G.Fabrizi Notes 160 1997 Awards. Book Review 161 Mechanism of transdermal drug delivery. Drug and Pharmaceutical Sciences. Series/8 Russel O. Pohs a nd Richard H.Guy Editors Index 162 lndex to Volume 15, 1997 XIX Announcements Clinica! Design Group lnc. - Seminar Series for Medicai Devices San Diego, CA . January 13/ 22, 1998 6th Congress of European Society for Pediatrie Dermatology Rom e, ltaly. September 14-1 8, 1999 • ,.,,_lh,........ CARTA ECOLOGICA· ENVIRONMENTALLY PAPER • PAPIER ECOLOGIQUE • PAPEL ECOLOGICO ~ ~ J Appl Cosmetol 15, 115-123 (October-December 1997) BIOLOGICAL FUNCTIONS ANO THERAPEUTIC PROPERTIES OF UREA W, Raab* ·Allergy Clinic 'lnnere Stadt' in Vienna, Austria Received: October 25, 7995 Key words: Urea, Dry skin, Atopy, Glucocorticoid, Moisturizer, Synopsis Although urea is know for about 50 years, its use as a topica! drug or as an adjunct is obtaining more and more attention in topica! dermatotherapy, Urea is absolutely non-toxic, undesirable actions occur only, if skin state and concentration of urea are on a disbalance. Urea proved to be a most valuable substance for restoring hydration in dry skin and in eczemas due to skin dryness. Therefore, urea ranks among the standards in atopy, for the treatment of eczema as well as for the interval care. Riassunto Sebbene si conosca l'urea già da circa 50 anni, il suo uso come farmaco o cosmetico topico sta ottenendo sempre più attenzione nella dermoterapia topica. L'urea è assolutamente atossica e si possono verificare effetti indesiderati solo nel caso in cui le condizioni della pelle e la concentrazione di urea siano sbilanciate. L'urea ha provato di essere una sostanza di grande valore per il ripristino dell'idratazione nella cute secca e negli eczemi causati dalla cute secca. L'urea si colloca quindi tra le scelte standard nei casi di atopia, per il trattamento degli eczema e per le terapie di intervallo. 115 810/og1cal funct1ons and therapeutic propert1es of urea INTRODUCTION Urea (carbamide), the diamide of carbonic acid. is a naturally occ uring degradation product of various prote ins in man. Up to 30 g were produced dail y. Urca is found in ali organs and body liquids. On thc skin s urface, urea is an important component of the natural moisturi zing factor containcd in the hydrolipid e mu lsion. About 50 years back, urea was reccommended for the top ica! treatm e nt of hand eczema but onl y 30 years back. the first experimental data were collected on its biochemical and pharmacolog ical acti vi ti es. The moi sturiz ing capacity of urea in the s tratum corneum, especia lly in xerotic states, was discovered. In 1988, a symposium was he ld in Salzburg, Austria, the proceedings of which contain all the information available on the various acti ons of urea in dermatology and cosmetol ogy ( 1). The more recent pubblications are compi led in a rev iew article published 1993 (2). Today, urea belongs to the standard s ubstances used in dermatolog ica! therapy and skin care. TOXICITY Urea lacks any systemic tox ic ity. Urea formerly was used as a diurctic drug; doses up to I .O g/kg bodyweight were given intravenously, without any undesirable action. Therefore, fo ll owing absorption from exte rnal pre paration s, no tox ic effects o f urea can be found. T he tolerance of urea de pends on the state of the skin and on the concen tration of urea. The vehi cle applied may influence the tolerance, too. On health y s kin , urea may be used in concentra tion s up to 20% . Most products, however, contain 5- 10% of urea, onl y, as iffitating effects on slightl y da maged s kin s hould be avoided. S uch e ffec ts might develop as a co nsequence of osmotic act ivity. 116 BIOCHEMICAL FUNCTIONS OF UREA ON THE SKIN Urea is an important component of the natural mo is turi z ing factor of the stratum corne um. Water is bound by a n inc lusion in the c rysta l s tru ct ure o f urea and o nly s lowly liberate d. Urea s tems from the sweat a nd from the process o f keratinization. The natural moi s turi z ing fac to r co ns is ts of va ri ous ions (24%), py rrolidone carbo xy lic acid ( 12%). va riou s o the r ca rb oxy l ic ac id s (50%), am ines and am ides ( 17%) and urea (7%). One s hou ld not undcrsti mate the amount of natural mo is turi z in g fac to rs in the s tratum corneu m w ic h make up abou t 25% of the d ry weig ht of the total horny layer. S tratum co rn e um of health y sk in co ntain s about 40 M urea per lo M amino acids w hich co rrespo nd s to about 28 µ g/2.5 c m2 (2). In dry sk in , urea conte nt is signi ficant ly lowe r (50% in some ins tances, only). C lin ically normai s kin of a topic individuals cont a ins o nl y 30% urea compared to normai va lues. In c li ni c all y d iseased s kin (a topi c eczema), urca co nte ni is lowered to 20% of no rm a i va lu es (Fig. 1, 2). From these data the co nc lu sion may be reached tha t urea is one of the m ost im portant components of the natural moi sturizing factor of human sk in. MOISTURIZING ACTIVITY OF UREA Urea exerts a wide ra nges of pharmacological acti vities when applied on the skin: - moisturi z ing acti vity, - desquamating actio n (lysis of cementing subs tance), - an timicrobial action (uptake of wate r in terferes with the growth requirements of microorganisms), WRaab U RF. \ IN HUMA'I SKI:\ µg/ 2.5 cm.! 30 29.8 lo~d pm cm 2 27.9 25A 20 16.1 13.7 12.3 10 Tot:.tl Fcmalc' 10-' Normai SkinO Fig. I UREA IN ll U\l AN SKIN, R EI.ATEO TO AGF. A'> D DRYNESS 25 µg/2.5 cm' 20 15 IO 101 IOOOmin ··-----·· 16 - 20 a lleallhJ Sk in 0 .11 - 40 a 21 - 30" Skin of Alopic l'cr~ons A•-----.t.a 0 Atopic Ectcma O Fig. 2 60 ••t------i•• 1orr urca in \\ ater-i n-oil emulsion "•1ter-in -oil emulsion <ilone trilialcd "ater alone Fig. 4: The influence of ureo on the water binding copocity of humon strotum corneum (Wohlrob from 3). %"/n \\:ll cr u ptnkc 50 40 30 20 IO Il 20 34 Normai o 23 38 P,orimic nd: noi done Pl:iin \\'::Her O 4Mll glJcerol O o nd 58 lchthyo1ic 5.1\111 urca 13 Fig. 3: Water uptoke of normai, psoriotic, ond ichfhyotic strotum corneum following immersion in vorious solutions (Swonbeck, from 3). - "antiinfl amma to ry" acti o n (antipro li fe rat ive, anti edcmatous, antipruritic). - enzyme inh ibiting actio n (mostl y against proteases) and - keratolyt ic act io n (true ke ratinolys is occurs under the influence of urea in a concentration o f 40%). T he mos t impo rtant (and therapeuticall y most w ide ly used) ac t ion of urea is its moist uri z in g capac it y. By imm e rs ing s t ra tu m co rne um fro m dry skin (psoriati c, ic hthyotic) in S M ure a/ I, the uptake of water could be sig nifi cantly inc reased. In these experimen ts, urea sho we d definite ly high e r a c tivity t han g lyce ro l, a hum ectant whi c h is w ide ly used in cosme ti c produc ts. In another se ries of e xpe rime nts, tritia ted wa te r was applie d o n the s kin s ur face in th e fo rm of a wa te r-in -oi l 117 81olog1col tunct1ons and theropeut1c propert1es of ureo emulsion with 10% urea . The water retention , judged b y ho w long tritiated wa ter could be detected and in which amount, was s ig nificantly higher than in the controls with the vehicle alone. (Fig.4). The application of urea containing emuls ions decreases skin roughness due to the mo isturizing action of urea; maybe, the desquamating action of urea contributes to this effect. In atopic skin, this decrease in roughness, judged by the repli ca method , was expec ia ll y pronunced. (Fig. 5, 6). A vast number of experiments has been conducted to ascertain the moisturizing property of urea (figures 3, 4, 5, 6). Various methods have been used to probe this effect: corneometry, measurement of conductivity, evaporimetry and profilometry. By electron microscopy, a loosening of the Jayers within the stratum corneum could be demonstrated, indicating a moisturizing effect (2) . Cf. Fig. 7 , 8, 9. In diseased skin , too, experimental investigations have been performed to demonstrate the moisturizing (and antieczematous) action o f urea. In the European Study (Barcelona, Hamburg, Vienna) a statistically significant increase in mo isture and a statisticall y significant decrease in TEWL occu rred following a fo ur week treatment of atopic eczema with a preparation containing I 0 % urea (4 ). Cf. Fig. I O. % decrease of roughness parameters 30 20 IO Placebo Stan Urca cream Fig. 5: Decreose of skin roughness porometers RZ ond RA 60 min. otter the oppticotion of o silicone-contoining woter-in-oil emutsion with 5% ureo os compored to the vehicle without ureo. Meon volues of ten normai individuo/s were given (Puschmonn from 3). % dccrease or roughness parameters 30 20 KERATOLYTIC ANO DESQUAMATING PROPERTIES OF UREA In concentrations up to 20%, urea exerts a concentration-depending desquamating action on the stratum comeum. By this effect, skin penetration is facilitated. Cf. Fig. IO, 11. In a 40% concentration, urea has been shown to exert true keratinolytic properties. Nail plates in fungal diseases may thus be dissolved. 118 10 Stan I day 5 day 8 day Fig. 6: Decreose of skin roughness porometers RZ ond RA following the use of o silicone-contoining woter-in-oil emulsion with 5% ureo. Meon volues of 9 o topic individuols were given (Puschmonn, from 3). W Roob 140 ,.--~~~--t•t-~~~-·~~~---i·---------. 130 '' 120 ..:': '' '' :,,' ' '' ' 110 ' '' ' ' '' " ' .......... .. .. ...... .. -·------ --------·------------..... -------------·------------··:& 60 90 75 105 120 time/min ••1----~•• Oil-in-water emulsion with 5% urea •a-----..,•• Oil-in·water emu lsion without 5% urea ••1----~•• Untreated control site Fig. 7: Skin moisture ofter opp/icotion of o silicone-contoining oil-in-woter emulsion with ond without 5% ureo. meosurement by determinotion of the dielectric constont. Meon volues of 35 heolthy individuols were given. (Puschmonn, from 3). 140 130 120 110 100 90 IO Pre-treatment phase .Àr.ol~----•• Placebo 15 Treatment phase ••1-----•• 25 Post-treatment phase days 5 % Urea Fig. 8: Skin moisture following the opp/icotion of o silicone-contoining oil-in-woter emulsion with ond without 5% ureo tor two weeks. Meon volues of 6 heolthy individuo/s were given (Puschmonn, from 3). 119 Biologica! functions and therapeutic properties of urea Fig. 9: Hyperkerototic skin in chronic eczema before ond offer the opplicotion of ureo 10% + solicylic acid 5% tor 10 days. REM materio/ from biopsies, mognificotion 2.5(),J x. From 2, with the permission of the outors Plugshoupt ond FrCih. European Study 10% Urea in Chronic Eczema Hydration TEWL +80% 69U(!) +30%(!) Start 4 wceks Start C oncomitant cli11ical ammelioration Fig. 10 120 D 4 wceks WRaab ANTllNFLAMMATORY ACTIONS OF UREA USES OF UREA IN DERMATOLOGY An antiproliferative effect of urea has been demonstrated in states of accelerated cellular turnover (e.g. psoriasis vulgari s) but no atroph ogenic effect in norma i skin could be observed. The antiedematous ac tion of urea is c onnected with its diuretic acti vity. In states of lymphostasis, a dramatic response can be evoked by topic a! applications of I 0% urea. The antipruritic acti vity of urea mainl y is due to its moisturi zing capacity. On the other hand , a directed influe nce of urea on those enzymatic activ ities whi ch provoke itch could be de monstrated. Urea alone ANTIMICROBIAL ACTIVITY OF UREA By its strong wate r binding capac ity, urea inhibits the growth of mic roorganisms. Therefore, urea may be regarded as a preservative-saving substance. Dry skin , old skin , photodamaged skin. Atopic skin , (therapy and interval skin care). Psoriasis vulgaris and other scaly derm atoses. Ichth yosis and ichthyos iform skin c onditions, hype rkeratoses, keratose s. Onycholysis (40%!) Urea in combinations With glucocorticoids (hydrocortisone, halc inonid): atopic eczema, chroni c dry eczema, Psoriasis vulgaris, ali old, hype rkeratoti c, scaly, resistant inflammatory skin lesions. (5-1 0% urea, O, 1- 1% steroid). With anthralin ( 17% urea + 0,5-2% a nthral in): Psoriasis v ulgaris, prolonged app licati ons or short contact therapy. M"ale score Trnnsmissio n ( 1apc mcthod ) UREA COMBINED WITH OTHER DRUGS Via three mechanisms, urea increases the pharmacological acti vities of othe r simul taneously applied drugs: - v ia its moi sturizing ca pac ity (inc re ased absorption), - via its desquamating properties (increased absorption) and - vi a the formation of hydrophilic adducts (incre ased re lease from the pre paration and in creased uptake by the skin). Lastly, synergistic effects much be mentioned between urea and some topically applied drugs with antiinflammatory or ke ratolyti c acti on. An e xample is shown in Fig.9. 80 2.5 60 ~o 1.5 20 0.5 O C \' J'k U IOL C: Control V: Vehicle Fig. 11 - Desquamating action o f urea 12 1 81olog1col funct1ons ond theropeut1c propert1es of ureo With polydocanol (5% urea + 3% polydocanol): atopic eczema, treatment and interval skin care. With tretinoin (10% urea + 0,03% tretinoin): non-inflammatory, non-erythrodermic ichthyosis. With salicylic acid (10% urea + 5% salicylic acid): stubborn hyperkeratosis, corns, eventually warts. With bifonazole (40% urea+ 1% bifonazole): onychomycosis. Among the combinations of urea with other drugs, the preparations containing urea and a glucocorticoid have found widest application. Urea increases the biovailability of the steroid ("hydrocortisone develops into triamcinolone") but does not alter the incidence and severeness of undesirable effects. 122 W Raab REFERENCES 1. Raab, W. (Editor) (1989), Harnstoff in der Dermatologie, Hautarzt 40, Suppi. IX. 2. Raab, W. (1993), Harnstoff in der Dermatologie, TW Dermatologie 23: 257-269. 3. Raab, W. (1990), Use of urea in cosmetology, Cosmet. Toiletr. 1054: 97-102. 4. Vilaplana, J. et al. (1994), Jnternationale, multizentrische Prilfung der Wirksamkeit und Vertraglichkeit der externen Therapie chronischer Ekzeme mit ei nem 10% igen Harnstoffpraparat, Akt. Dermat. 20: 227-231. Author Address: Univ. Prof Dr. W. Raab Walfischgasse 3 A - 1010 Vienna, Austria 123 J. Appl Cosmeto/. 15, 125-131 (October-December 1997) PRACTICAL TREATMENT OF DRY SKIN W. Roab• · Medicai Director, Allergy Clinic ' lnnere Stadt' Vienna , Austria Received: October 25, 7995. Key words: Dryness, Moisture, Ultraviolet, Age, Phot odamage, At opy. Synopsis Dry skin rnay result of exogenous or of endogenous factors. Exogenous fac tors may be excluded by informing the patient of his fa lse behaviour. If endogeno us factors are the cause of the dry skin state, reasonable measures of skin cleansing, skin care and skin protection sho uld be considered. Riassunto La pelle secca può essere il risultato di fattori esogeni o endogeni. I fattori esogeni si possono eliminare facendo presente al pazie nte il suo comportamento errato. Nel caso invece in cui siano fatto ri endogeni la causa della secchezza della pelle, dovranno essere prese in considerazione misure adatte per la sua de tersione, cura e protezione. 125 Proct1cal treatment of dry sk1n INTRODUCTION Water is the softener of the horny layer and sec ures smoothness, elasticity and suppleness. Under normai conditions, water enters the horny Iayer via transdermal diffusion (TEWL). The evaporation of water from the skin surface is prevented by the action of the natural moistourizing factors (NMF). The water balance of the horny layer is depicted in figure 1, the composition of the NMF is shown in figure 2. Dry skin is either caused by external factors or by endogenous changes. EXTERNAL CAUSES OF DRY SKIN Among the external causes of dry skin, abuse of soaps and detergents must be mentioned on the first hand. But often a prolonged contact with water is the reason for skin dryness, as the NMF is dissolved and rinsed off. For facial skin, prolonged exposure to a dry environment causes skin dryness, unless the water loss is prevented by the application of moisturizing skin care products. ENDOGENOUS REASONS FOR DRY SKIN Water balance of the horny layer Evaporalion ~ D Drv, air movement fewNMF, large surrace Fig. 1 NMF of Human Skin There are three endogenous reasons for dry skin: - constitution, especially atopy, - genetic ageing and - photodamage. In atopy, the disturbed barrier function must be regarded as the main reason for skin dryness. Furthermore, there is almost always some inflammation present which causes skin dryness. In senile skin, water Ioss is increased due to the numerous wrinkles and folds wh ich increase the surface. Furthermore, water supply is decreased as generai circulation is reduced and an atrophy of rete plugs occurs (reduced size of the contact area with the supplying derma! tissues). In photodamage, the surface is even more increased than in senile skin as there are numerous wrinkles and deep folds (elastosis); solar keratoses provoke a further increase in water loss. - The mechanisms for endogenous dry skin are depicted in figure 3. SIGNIFICANCE OF DRY SKIN Fig.2 126 For the patient, dry skin causes an unpleasant "old and neglected" appearance. Steady application of skin care products is needed to counteract W Raab itch and tension. From the dermatologica! point of view, dry skin often is the cause of eczemas and infections, especially in older persons. REGIMEN IN DRY SKIN Three important measures have to be taken to cou nteract dry skin and to prevent the disturbing consequences of this skin state: - mild, non-alkaline skin cleansers, - regular application of O/W or W/0-emulsions with moisturizing compounds, and - skin protection against ali kinds of environmental influences (ultraviolet, heat, cold). CLEANSING MEASURES IN DRY SKIN Skin cleansing may be effectuated by the application of - natural (soaps) and synthetic detergents (syndets), - adsorptive cleansing agents (e. g. oatmeal), - desquamating agents ("exfoliation") and peeling agents, - dermabrasive agents, e. g. polyethilene granules (cf. 2,5). The best way of cleansing dry skin is the use of slightly acid, mild detergents. In cases of very sensitive skin, in atopy or in atrophic skin, the use of adsorptive complexes should be preferred. Oatmeal extracts, prepared for cleansing purposes, contain complexes consisting of polysaccharides, oligosaccharides, oils and proteins. That means that the complex exhibits lipophilic and hydrophilic groups on its surface thus permitting the removal of lipophilic and hydrophilic "dirt" (substances from the environment, decomposition products of sweat, sebum and topically applied preparations) by adsorption. Figure 4 demonstrates the roughness of the skin surface following the use of soaps, detergents or adso1ptive cleansing agents with smoothing additives. Fig. 3 SKIN ROUGHNESS AFTER CLEANSING 20- 15 10- - - - ~- Sta ri value - - - - - - 5- ------------------------- ----------------· / Soap O il bath Sinder and additives Adsorptive cleanser and addith·es Fig. 4: Skin roughness affer different forms of cleansing, determined by the colour retention method 127 Proct1col treotment of dry sk1n SKIN HYDRATION Skin hydration may be effectuated by the appl ication of e mollients (pseudo-occlusi ve effect closi ng small clefts on the surface of the stratum co rne um), by the a ppli cation of mois turin g compounds, or by the increase of oxygen tension in the stratum corneum. The various possibilities of increasing hydration in the stratum corne um are depicted in figure 5. Among the moisturizers, humectants (e. g. glycerol) and moisturizers have to be me ntioned. Mo isturi ze rs s uc h as mucopol ysacch arid es (hyaluronic ac id) are preferable as they retain water even in a dry environment and offer it to the horny layer. Under such unfavorable cond iti ons, humectants may eve n wi thdraw water fro m the skin (cf. fig ure 6). T he obse rva ti o n that oxygen tens ion in th e horn y layer decreases steadily wi th inc reas ing age (figure 7) has provoked investigations of the changes in dry skin follo wing the application of oxygen de livering preparations ( 1). In fac t, applications of a cream containing oxygen (4,5%) in 10% perfluordecaline signi ficantly increases oxygen tension in the horny layer as compared to the vehicle (6,7). Cf. figure 8. Para llel to the increase in oxygen tension an increase in moisture was noted (figure 9). Furthermore, wrinkle number and depth decreased under the influe nce of an oxygen de!ivering cream (figure I 0). Fig.5 WATER UPTAKE (g/lOOg) 100% Relali"e humidity: 33% I Rela ti"e humidity: 75% I 80% 60% P) rolidone carbo~y l ic acid O Glycerol O Fig. 6: Water uptoke by different moisturizing compounds. hmuectonts ond true moisturizers depending upon the humidity in the environment 128 W Raab OXYGEN IN AGEING SKIN 40 "" ~ = = 30 o ............ Q. 20 -----.:::':"::".:":~:::::::o=:'lll'9~.............. ~~~~~~~~~~~~ Rise factors for microangiopathia ---------- IO age o 20 30 50 40 60 Fig. 7: Oxygen pressure in the skin, depending upon age. Note the reduced oxygen pressure in persons with risk factors for micorangiopathis such as cigarette abuse OXYGEN IN HUMAN SKIN 40 4.5% 02 in PerOuordecaline (hvice daily) 30 20 days IO 8 12 16 20 24 28 Fig. 8 90 SKIN MOISTURE ::= ~ ~ ~ 80 70 ~ STOP ~ 3 E o u 4.5 % 02 in 10 % Perfluordecaline (twice daily) 60 50 40 days JO 4 12 16 20 24 28 Fig. 9 129 Proct1col treotment of dry sk1n SKIN PROTECTION Most forms of environmental stress increase skin dryness. Therefore, protection against physical influences or, even better, avoivance of those plays an important role in treatment and prophylaxis of dry skin states. Ultraviolet irradiation , UVB as well as UVA, provokes skin dryness due to alterations of the epidermis and the dermis over the years (3, 4). As it is non realistic to try to keep people out of the sun, doctors should advise their patients to apply sun protecting creams in a reasonable manner. DEPTH ANO NUMBER OF WRINKLES AFTER OXYGEN SUPPLY (14d ) 30 15 20 10 10 5 Fig. 10 130 Number Deplh W Raab REFERENCES 1. Artmann, C. et al.(1993), Sauerstoff in der Haut. Ein neuer Parameter der Hautalterung, SOFW J ournal 1993 15, l -5. 2. Raab, W. (1990), Skin cleansing in health and disease, Wien. Med. Wschr. 140, Suppi. 108. 3. Raab, W., Zeitalterung und Umweltalterung der Haut, hautnah 611994 Dermatologie, 589-594. 4. Raab, W. (1994), Reinigung, Pflege und Schutz der Altershaut, Handbuch der Gerontologie. Bd. 7, 365-388, Fische1; Stuttgart, l ena, New York. 5. Raab, W. und U. Kindl (1997), Pflegekosmetik. Fischer und Covi, Stuttgart und Eschhorn (2 11d ed.). 6. Stanzi, K. et al.(1993), A new cosmetic product containing molecular oxygen, Eurocosmetics 1993 l , 1-6 7. Zastrow, L. et al., The effectiveness of molecular oxygen in cosmetic form ul ations, In press. Author Address: W. P. Raab, M. D., FAAD Professor in Dermatology 3, Walfischgasse A-1010 Vienna, Austria 131 ' J. Appl Cosmetol. 15, 133-138 (October-Oecember 1997) A COMPARATIVE OOUBLE-BLINO WITHIN SUBJECT STUOY OF THE EFFICACY ANO TOLERABILITY OF TWO OIFFERENT OERIVATIVES OF VITAMIN A ON SKIN THICKNESS ANO ELASTICITY: RETINOIC ACIO ANO CONJUGATEO RETINYL PALMITATE Erling Thom, Ph,D, • "Medstat Research Ltd, Lillestn2im, Norway Received: June 78, 7997. Key words: Retinyl palmitate. Retinoic acid. C omparative study, Skin elasticity, Skin thickness. Synopsis A randomized comparative double-blind within subject study of topica! administration of two differe nt Vitamin A preparations - conjugated retinyl palmitate, RP (0,2%) and retinoic acid, RA (0.025%) for 3 months in 20 females caused significant changes in skin thickness and elasticity as well as in the participants own judgment of skin improvement using visual analogue scales. The results indicate that both galenica! formulations exert a comparable effect, while the tolerability of the RP formu lation was significantly better. It might be of great importance for the efficacy of the RP cream that the compound is conjugated and thus hav ing a better skin biovalability than unconjugated RP has. Whether the clinial effect is due to metabolism of RP to RA or re tino! in the skin can not be answered by this study, but should be subject to further percutaneous absorption studies. Othe r studies indicate that the mechanism of action for RP creams might be due to biotransformation to retino! rather than to RA. Riassunto Uno studio randomizzato a doppio-cieco è stato condotto per tre mesi su 20 donne utilizzando due divers i preparati a base di vitamina A: retini! palmitato coniugato (RP 0,2%) ed acido retinoico (RA 0.025%). Le due formulazioni hanno provocato cambiamenti significativi sia nello spessore che nella elasticità della pelle . I risultati indicano che entrambe le formulazioni galeniche svolgono un'attività paragonabile, ma la tollerabilità della formul azione RP è stata significati vamente maggiore. Potrebbe essere di grande importanza per l'efficacia della formulazione RP il fatto c he la miscela sia coniugata ed abbia perciò una biodisponibilità cutanea migliore rispetto ad un RP non coniugato. Questo studio non ha potuto rispondere al quesito se l'effetto clinico sia dovuto al metabolismo dell'RP che si trasforma in RA o in retinolo nella pelle. Questo argomento dovrebbe essere oggetto di ulteriori studi sull'assorbimento percutaneo. Altri studi indicano che il meccanismo d'azione delle creme RP può essere dovuto alla biotrasformazione in retinolo, piuttosto che in RA. 133 A comporot1ve double - blmd wlfh1n sub;ect study of the eff1cocv ond tolerob111tv. INTRODUCTION Data has previously been reported on the efficacy and tolerability of a skin cream containing conjugated Retinyl palmitate (RP) (1,2). The aims of these two studies were to investigate the effect of the cream on skin thickness and elasticity and in add ition to study the duration of the effect after treatment was stopped. From these studies we have clearly documented that use of conjug ated RP results in an increase in ski n thickness and an improvement in skin elasticity. These observations have been co nfirmed by others (3,4) using other measuring techniques. RP is a widely used ingredient in cosmetic formulations. Because it is the most stable of the available vitamin A esters it can be directly incorporateci into an anhydrous base or the oi l base of a cos metic c ream or lotion. RP is li pophilic and photostable. Ofter products containing RP are advertised as having benefica) effects on the appearance of the skin. A great number of products containing RP are marketed. Previous studies suggest that enzymes present in the skin metabolize RP during skin absorption. Esterase activity hydrolyzes RP to retino) (Vitamin A), wich is oxidized in many tissues to Retinoic acid (RA) primarJy by alcohol dehydrogenase. RP can therefore be class ified as a prodrug where the inactive RP is transformed to active substances by metabolic biotransformation reactions in the skin. Recently a number of studies have been carried out with RA c reams showing that this compound has a positive effect on photo-aged skin (5-8). Preparations containing RA have been registered in some countries as e thicaJ drugs for treatment of aging skin. However, one main drawback with this type of treatment is that a number of patients (4-10%) develop soreness in and miscolouring (redness) of the skin (6). As mentioned above RA has been convincingly documented as having an effect on the treatment of the aging skin and retino) is also a compound with know pharmacological activity (9). Pre- 134 vious studies have shown the formation of alltrans-retinoic acids after topica) application of ali-trans-retino! in vivo in hairless mouse skin (10). Recently, however, a study showed that retino! was the onl y de tectabJe metabolite following administration of RP both in guinea pig and human skin, while no retinoic acid was detectable ( 11 ). About 30 and 18% of topically applied RA were absorbed from an acetone vehicle by hairless g uinea pig and human skin, respectively. Less than I% of the applied dose of RP diffused from the s kin into the receptor fluid. In human skin, 44% of the absorbed RP was hudrolyzed to retino!. An essential prerequisite for an optimaJ pene tration of the lipohilic RP into the skin is to modify che solublity of the compound by the use of tweens ( 12, 13). The producer of the RP preparation used in this srudy has developed a process where RP in conjugated with a complex polysaccharide thereby making the compound water soluble. In thi s way the penetration of RP through the skin and into the diffusion celi receptor fluid is enhanced. The same technique has been used succesfull y to enhance the bioavailability of drug substances both administered perorally as well as topicall y ( 14). Based on the abovementioned infonnation and our previous experiences with conjugated RP, we decided to carry out a clinica) comparison on skin thickness and skin elasticity following treatment with an cream containing either RA or conjugated RP in order to gain an indirected impression of the bioequivaJency of these two substances. MATERIAL ANO METHODS The study was carried out as a randomized double-blind study in 20 femaJes with each participant using both formulations one on the right and the other the left volar (protected) part of the forearm, respectiveJy. The administration of the formu lations was randomized, such that haJf of the partici pants used formu lation A on th e E. Thom right arm and formulation B on the left ann and vice a versa for the other women. The tota! treatment period was 3 months and administration was b.i.d. (in the morning and evening) during the study period. The study was carried out in accordance with the Declaration of Helsinki. The investigational formulations The two formulations used in this study were: A conjugated RP cream made by Pedersens Laboratorium, Vejle, Denmark, containing 0.2% RP and a cream containing 0.025% RA made with the same cosmetic properties and apperance as the conjugated RP cream. Formulation A is identica! to the marketed preparations Sincera®, Demelle®, Luscinia® and Rebilt®. The investigational products were packed in identica! packages in order to keep the study blinded. Measurements of skin thickness and skin elasticity The measurements of skin thickness and skin elasticity were performed by ultrasound using Dermascan A and Dermaflex instruments, respecti vel y (Cortex Inc. Aa rhu s, Denmark). Measurements were carried out at baseli ne, after 1 month and after 3 months, by the same person (ET) on ali three occasions and measurements were performed at the mid-region of the volar part of the forearm. Ali measurements were in triplicate and average values used for statistica! evaluations. Se/f-eva/uation by the partecipant At the same time as each ultrasound measures was made, participants made a self evaluation of skin quality using visual analogue scales of 10 cm with endpoints of "no change" and "very pronunced change". Subjects were asked to sco- re the global change in skin quality by placing a mark on the line between the endpoints. The distance from the zero point (" no change") to the mark was used as the score for the subject. Statistica/ methods A significance level of 5% was used in the tests and two-tailed tests were applied. Mean was used for estimation of continous and near continous variables, and Student procedure was used for construction of confidence interval of the mean. The one-sample t-test was used analysing change over time within groups. Analysis of cavariance and two-sample t-test were used to compare arms with regard to continous variables. RESULTS 20 females aged between 40 and 60 years (mean 51.4 yrs) were included in the study and ali participants were compliant with the protocol. Ali participants gave their infonned consent to take part in the study after having received written and verbal infonnation about the study. Efficacy parameters, skin thickness and e/asticity The resu lts from the skin thickness measurements are shown in Table I. Formulation A resulted in a average increase in skin thickness of 3 1% compared with 33% for formu lation B. This increase in skin thisckness was significant (p<O.O 1) for both formulations, while the difference between the two formulations was not significantly different. In Table II the viscoelastic properties of the skin following administration of fonnulations A and B, respectively, are presented. The results show that formulation A improved the elasticity by 19% on average, compared with 20% for B. 135 A comparative double - blind within subject study of the eff1cacy and tolerability ... Both formulations improved the elasticity of the skin significantly (p<0.01), but again the difference in elasticity improvement between the two formulations was not significant. Efficacy parameters, self-evaluation by use of VAS The VAS results are shown in Table III. A significant impro vement (p<O.O 1) in skin quality was reported for both forearms. The difference in skin improvement between the two formulations is, however, not significant. Table I Changes in skin thickness (mm) after administration of conjugated RP (A) and RA (B) creams for 3 months, respectively (N=20) Formulation Mean (SD) Range Mean (SD) Range A B Initially 0.90 (0.12) 0.71-1.24 0.88 (0.15) 0.70-1.25 After I month 1.01 (0.17) 0.74- 1.27 1.02 (0.15) 0.76-1.30 After 3 months 1.18 (0.1 5) 0.90-1.34 1.1 7(0.17) 0.90- 1.37 Table Il Changes in skin elasticity (%) after administration of conjugated RP (A) and RA (B) creams for 3 months (N=20) Formulation Mean (SD) Range Mean (SD) Range A B Initiallv 59.3 (7.9) 44.3-81.0 60.0 (7.5) 45.4-80.8 After 1 month 65.2 (8.2) 50.2-81.2 67.2 (8.0) 46.4-81.6 After 3 months 70.6 (8.4) 51.3-85.0 7 1.2 (8.6) 52.4-86.0 Table lii Changes in VAS scores (cm) after administration of conjugated RP (A) and RA (B) creams for 3 months (N=20) Formulati on A B 136 Mean (SD) Range Mean (SD) Range After I month 1.8 ( 1.2) 0.0-3.5 1.9 ( 1.5) 0.3-3.4 After 3 months 6.3 (1.6) 1.0-8.3 6.5 (1.8) 1.2-8.6 E Thom Tolerability At each v isit subjects were asked if they had had any problems and/or side-effects with the treatments they had used. Seven of the subjects reported skin soreness after using the RA formulations and 2 of these aJso reported a considerable redness in the skin I/2- 1 hour after application. The reported sideeffects are, however, transient and none of the subjects stopped the treatment due to the sideeffects. One subject reported redness of the skin following administration of the conjugated RP formulation. The tolerability was significantl y in favour of formulation A, the conjugated RP formulation. This is also revealed in the preference choice from the users (see below). Preference choise from the subjects On completion, subjects were asked to give a preference for one of the two creams they had used taking into account the effect, the tolerability and the cosmetic properties of the creams. Thirteen subjec ts prefered the conjugated RP cream, formu lation A, whi le 4 prefered the RA cream, and 3 subjects had no preference. The difference in preference is significantly in favour of the conjugated RP formu lation. DISCUSSION the conjugated RP is significantly better than the RA, the conjugated RP may represent a valuable alternative to RA. As have been stressed by other investigators (3,4) it is of utmost importance that the RP is in a form allowing skin penetration. In a previous comparative study we reported a significant difference between conjugated and non-conjugated RP in the effect on the skin parameters (1). The change in solubility of the RP is probably essential for making the ester available in sufficient concentration. To our knowledge no percutaneous absorption and metabolism studies have been carried out with conjugated RP. Such studies are needed in order to explain the mechanism of action behind the effect seen in skin parameters measured. The minimal conversion of retino! to RA may not be relevant to the application of formu lations containing RP to the human skin. Both retino! and RA can have pharmacological effects on human skin. Retino! is about 50% as potent as RA in inducing epidermal hyperplasia in the hairless mouse ( 11 ). It has, however, been shown that retino! is formed in hairless guinea pig and human skin after topica! application of RP, but if further metabolism to R occurs, it is to small to detect. Any biologica! response of skin treated with retinyl palmitate formulations may be due to ester hydrolysis of the parent compound to retinol. The use of RP in cosmetic formu lations may result in a significantly improved delivery of retino! into the skin. In recent years knowledge of the effect and metabolism of vitamin A derivatives in the human skin ( 15, 16) has been accumulating. The results from the present study indicate that both, the 0.025% RA cream and a 0 .2% conjugated RP cream bring about a comparable effect in skin composition and morphometry. No significant differences could be detected either in sk in thickness or elasticity improvement between the two creams. As the tolerability of 137 A comporot1ve double - bilnd wlfhin sub;ect study of the eff1cocy ond tolerobillfy . REFERENCES 1. Thom E (1993), Skin treatment with two different galenica! fonnulations of retinyl palmitate in humans,J.Appl. Cosmetol. 11, 71-76. 2. Thom E (1994), Long-tenn effects after topica! application of active retinyl palmitate, J.Appl. Cosmetol. 12, 45-50. 3. Counts DF, Skreko, Mcbee J, Wich G (1988), The effect of retinyl palmitate on skin composition and morphometry, J.Soc.Cosmet.Chem. 39, 235-240. 4. Fthenakis CG, Maes DH, Smith WP (1991), In vitro assessment of skin elasticity using ballistometry, J.Soc.Cosmet.Chem. 42, 211-222. 5. Kligman AM, Grove GL, Hirose R, Leyden JJ (1986), Topica! tretinoin for photoaged skin, J.Am.Acad.Dermatol. 15, 836-859. 6. Weiss KS, Ellis CN, Headington JT, Hamilton TA, Vorhess KK (1988), Topica! tretinoin improves photoaged skin: a double-blind vehicle controlled study, JAMA 259,527-532. 7. Bhawan J, Gonzales-Serva A, Nehal K, Labadie R, Lufrano, Thorne G et al. (1991), Effect of tretinoin on photodamaged skin, Arch.Dermatol. 127, 666-672. 8. Rafal FS, Griffiths CEM, Cherie MRCP, Ditre M, Finkel LJ, Hamilton TA et al. (1992), Topica! tretinoin (retinoic acid) treatment for liver spots associated with photodamage, New Engl J Med. 6, 368-374. 9. Gilchrest BA (1992), Retinoid phannacology and the skin. In H. Mukhtar (ed.) Phannacology of the skin, CRC Press, Boca Raton, 167-181. 10. Connor MJ, Smit MH (1987), The fo rmation of all-trans-retinoic acid from ali-trans-retino! in hairless mouse skin, Biochem Pharmacol 36, 919-924. 11. Boehnlein J, Sakr A, Lichtin Leon J, Bronaugh RL (1994), Characterization of esterase and alcohol dehydrogenase activity in skin. Metabolism of retinyl palmitate to retino! (Vitamin A) during percutaneous absorption, Pharm Res 8, 1155-1159. 12. Jarrett A, Jackson RJ (1980), The effect of vitamin A on the skin and istrole as a cosmetic agent. Abstract 11 th lnternational I FSCC Congress Research and Technology. Venice 23-26 Sept. 13. Spearman RIC, Jarret A (1974), Biologica! comparison of isomers and chemical fonns of vitamin A (retino!), Br J Dermatol. 90, 553-560. 14. Paginton JS (1987), Beta-cyclodextrin: the success of molecular inclusion, Chemistry in Britain 23, 455-458. 15. Wolf G (1996), A history of vitamin A and retinoids, FASEB J 10, 1102-1104. 16. Fisher GJ, Voorhees JJ (1996), Molecular mechanisms of retinoid actions in skin, FASEB J 10, 1002-1013 Author Address: Erling Thom, Ph.D. P.O. Box 210 N-2001, lillestrç!Jm, Norway Fax: (+47)63.81.92.50 138 J Appl Cosmetol 15. 139-145 (October-December 1997) A NEW COSMECEUTICAL FOR THE "ORANGE PEEL" SKIN P, Morganti", S.D. Randazzo .. , G.Fabrizi ... end C. Bruno•••• • President/Director, R & D Mavi Sud S.r.l,, Viale dell'Industria l, 04011 Aprilia (LT), ltaly, Department of Dermatology, Dermatologists Training School, Il University of Naples, ltaly, •• Department of Dermatology, University of Catania, ltaly. ••• Department of Dermatology, Catholic University of Rome, ltaly. •••• Physiology lnstitute, University of Urbino, ltaly. Received: May 7, 1997 Presented at 2sd Symposium on Cosmetic Efficacy - New York, 28-30 Aprii, 7997. Key words: TCDS, Cellulitis, Orange-peel skin, Skin hydration, TEWL, 3C System®, Dermoscan e Synopsis "Cellulitis" represents an unaestheticism capable of modifying the harmony of the figure referring to modem rules. The skin opaque, arid, scabrous and painful to the touch is characterized by a rugged appearence known as "orange peel skin". The present study was designed to evaluate the activity of a new Transdermal Cosmetic Delivery System (TCDS) on the anterior lateraJ surface of the thighs of 30 female volunteers (aged 18-30) presenting cutaneous signs of "cellulitis" of different degrees of intensity, treated each night for 21 days with this special patch in a double blind study. Before and after the study the thickness of the cutaneous tissue was controlled by the Dermoscan C® (Denmark, vers ion 3 at 20-MHz) and skin hydration and TEWL by 3C System®(Rome, Italy). The TCDS caused a both a decrease of skin thickness, and of the cellulitic layer thickness and a contemporary high increase of skin hydration and TEWL (p<0.005). No adverse reactions were observed. The obtained results seem to prove the validity of this new cosmeceutical device for the treatment of the so called "cellulitis". Riassunto La "cellulite" rappresenta un inestetismo capace di modificare l'armonia della figura secondo i parametri moderni. La pelle opaca, arida, scabra e dolorante al tatto è caratterizzata da un aspetto ruvido noto come "pelle a buccia d'arancia". Con il presente studio si è voluta valutare l'attività di un nuovo cerotto transdermico denominato Transdermal Cosmetic Delivery System (TCDS). La valutazione é stata effettuata sulla superficie antero-laterale delle coscie di 30 donne volontarie (di età compresa tra i 18 e i 30 anni), che presentavano segni cutanei di una cellulite con diversi gradi di intensità, trattate ogni notte per 21 giorni 139 A new cosmeceut1cal tor the "orange peef" sk1n con questo speciale cerotto in uno studio a doppio cieco. Lo spessore della pelle è stato controllato prima e dopo lo studio tramite il Dermoscan C3 (Denmark, versione 3 a 20 MHz), l' idratazione della pelle e la TEWL per mezzo del 3C System*. Il TCDS ha provocato una diminuzione dello spessore della pelle, una diminuzione dello spessore dello strato di cellulite ed un contemporaneo aumento sia dell 'idratazione cutanea globale (p<0.005) da addebitarsi essenzialmente all 'attività occlusiva esercitata dal cerotto, che del TEWL. Non sono state rilevate reazioni collaterali. I risultati ottenuti sembrano provare la validità di questo nuovo mezzo cosmetico per il trattamento della cosiddetta "cellulite". 140 P Morgonlt, SO Rondozzo. G Fobrtzt, C Bruno INTRODUCTION "Cellulitis" represents an unaestheticism capable of modifying the harmony of the figure referring to modem rules. The skin opaque, arid, scabrous and painful to the touch is characterized by a rugged appearence known as "orange peel" skin (1 -3). STUDY DESIGN The present study was designed to evaluate the acti vity of a new Transdermal Cosmetic Delivery System (TCDS) on the anterior lateral surface of the thighs of 30 fornaie volunteers (aged 18-30) presenting cutaneous signs of cellulitis at d ifferent degrees of intensi ty, localized on the a nterio r-lateral surface of thighs, treated each nig ht fo r 21 days with this special patch (4x4 cm ) in a double blind study. In order to eli minate possible extemal influences 15 women were randomly treated on the ri ght or on the left thigh with both the active-patc hes or with the vehicle-patches (contro! ), the othe r side serv ing as untreated contro!. In this way both the active and the con tro! patches were indifferently applied both on the right and the left ti gh. The selected subjects were not taking drugs for systemic administration or ant i-cellulitis topic products and, moreover, had not undergone specific diets before a nd during the clinica! trial 's period. INSTRUMENTAL MEASUREMENTS Ulfrasound-8-mode imaging This two-d imensional B-scan procedu re gives ultrasounds single lines (A-Scan lines) corresponding to a cross-sectional image of the skin. In fac t when a beam of ultrasounds passes through the differe nt layers of the skin, different echoes are produced depending on the acoustic c haracteristics of the exam ined areas ; those echoes are recorded by the instrument and vi sualized on the screen as peaks (A-Scan). By measuring the dista nce among the peaks, it is possible to determine the th ickness of the different structural components of the skin (I 0). Before and after the study the thickness of the subcutaneous tiss ue was controlled on 3 points of skin surface for both the thighs by the Dermoscan C®, (Denmark) version 3, at 20-MHz. Skin hydration and TEWL were controlled by 3C System®, (Rome, Italy) wh ich was previously used by our team (I I). 3C System® This computerized system through the capacitative resistance permits a simple and quick contro! of surface lipids, skin hydration and TEWL The 3C System® collects up to 10/15 measure- MATERIALS ANO CHEMICALS I. 4x4 cm patch with acrylic base (vehicle-contro l B); 2. 4x4 cm patch enriched with centella asiatica and fuc us ves icolosus extracts so that each plaster contains a tota! of I O mg active compounds, 0.2 mg/cm 2 of whic h are centella tri- terpens (4-9). 3C System® 141 A new cosmeceutrcal far the "orange pee/" skrn ments over 25 seconds sampling period and records the mean value automatically standardizing the environmental conditions (RH=50%, T=22°C). Measurements were performed on lst day (baseline) and after 7, 14, 21, 28, 35 days. TEWL is expressed as the amount of water evaporated per unit of surface in 1 hour gr/m2/h and the system collects up 10/15 measurements over 25 second sampling period and record the mean value automatically (11). Statistica/ analysis Differences in TEWL, skin hydration and subcutaneous tissue thickness were examined for statistica! significance using the non-parametric Friedman test. When the Friedman test revealed significant values between the treatments, multiple comparisons of all groups were conducted by the Wilcoxon-Wilcox tests. RESULTS Tue obtained results are reported in Fig. 1, 2 and 3. COMMENTS As already proven by our group and by other authors the scan-ultrasound tecnique seems to be the best methodology feasible for measuring the variations of the cellulitic layers during an anti-cellulitis treatment (12-18). As it can be seen on Fig. 1 patch application on day 21 highlights a remarkable change in the thickness of the cutaneous layer (p<0.005) before and after the treatment. This change is surely due to the activity carried out by the used active ingredients, since the sole vehicle has proved to be ineffective. It is also interesting to point out that the patch- SUBCUTANEOUS TISSUE THICKNESS BEFORE ANO AFTERTREATMENT BY AN "ANTl-CELLULITIS" PATCH Time =21 days (One patch daily) - n =15 - RH =50% - t =22 •e 5,70 5,65 5,60 5.545 :!: 0.521 5,55 5,50 ~ 5,45 5,40 5,35 5,30 5.2A5 :!: 0.641 5,25 5,20 5,15 Baseline Mean Value Untreated Final Mean Valuo Vehicle Patch Final Mean Value Active Patch Active-Patch values are highly significant as Baseline and Vehicle (p <0.005) Fig. 1 142 P Morgont1, SO Rondozzo G Fobnz1 C Bruno TEWL OF THIGH-SKIN TREATED BY "ANTl-CELLULITIS" PATCHES UNTREAi ED 2 0 +-~~~~~+-~~~~~+-~~~~~+-~~~~~+-~~~~--l o 14 7 I c:=Juntreated Skin A rea Untreated Versus Patch-Treated (Vehicle and Active) 28 21 - - - Vehicle Patch-Treated 35 DAYS ........... Aclive Patch-Treated I =p < 0 .005 - Active-Patch Versus Vehicle-Patch =ns Fig , 2 HYDRATION OF THE THIGH-SKIN TREATED BY "ANTl-CELLULITIS" PATCHES n =15 - RH =50% - t =22 •e 70 60 56,7 :t 1 50 w (/) ~ 40 "' u ;!!; z 30 o ~ o >:z: 20 .... 10 o o 7 14 21 28 35 DAYS I-+- VEHICLE PAT CH ..... ACTIVE PATCH I Patch-Treated versus Baseline = p < 0.005 - Vehicle-Patch versus Active-Patch = ns Fig , J 143 A new cosmeceutical for the "orange pee/" skin treatment causes the TEWL to increase considerably (p<0,005), indipendently from the presence of the active ingredient. This means that it acts by changing the stratum corneum barrier. That should be the reason why the active ingredients seem to be able to easily reach the hypoderm. By interrupting the treatment TEWL gets back to normai values (p<0.005) (Fig. 2). Also concerning the cutaneous hydration the increasing problem is due also to the occlusive effect caused by the patch (p<0,005) (Fig. 3). No adverse reactions were observed. Obtained data seem to confirm what we previously proved (4-8), i.e. that the TCDS (Transdermal Cosmetic Delivery System) is an helpfui cosmeceutical device, easy and quick to use, and capable of giving good results in the treatment of the cutaneous unaesthetism called "cellulitis". Aufhor Address: P. Morganti, PhD - Research and Development MAVI Sud srl - Via del!' Industria I, 04011 Aprilia (LT) , ITALY Phone: + 39 06 9286261 Fax:+ 39 06 9281523 [email protected] URL=http:// www.colosseum .itlst81 /mavì 144 P Morgant1. SO Randazzo. G Fabnzi. C Bruno REFERENCE 1. Braun Falco O., Scherwitz C. (1972), Histopathologie der Sog. Zellulitis. Hautartz, 23, 71 -75 2. Binazzi M., Papini M. (1983), Aspetti chimico-istomorfologici. In: (Ribuffo-Bartoletti eds) La cellulite, Ed. Salus Internazionale, Roma, Italy 3. Scherwitz C., Braun Falco O. (1978), So-called cellulitis, J.Dermatol.Surg.Oncol. 4, 230-234 4. Morganti P., Celleno L. and Vasselli A. (1995), A new Transdermal Delivery Cosmetic System to contro! the skin localized lipodystrophy, J.Appl.Cosmetol. 13, 15-20 5. Morganti P. (1995), Nuove applicazioni di principi attivi vegetali: il cerotto cosmetico, Cosm. News, 107-109 6. Morganti P., Tiberi L., Vasselli A., Tolaini M. V., Serafini G., Celleno L. (1995), Transdermal Cosmetic Delivery System: a new device for cosmetic use. Evaluation of its effects in the treatment of so called "cellulitis", Presented at IFSCC Congress, Montreux, Switzerland, 18-21 September 1995 7. Morganti P. (1996), The cosmetic patch: a new frontier in Cosmetic Dermatology, Soap, Cosm. Chem. Special. (February), 48-50 8. Morganti P, Fionda A., Tiberi L. (1996), The TransdèrmaJ Cosmetic Delivery System: A new cosmeceutical device, Presented at Active lngredients Conference, Paris 13-14 November 1996, in print on Cosmetics & Toiletries. 9. Morganti P., F ionda A., Tiberi L., Icare M., Rusch F., Elia U. (1996), Extraction, analysis by HPLC of cosmetic active ingredients from an anti-cellulitis transdermal delivery system, Submitted for pubblication. 10. Seidenari S. (1995), Ultrasound B-mode imagine and in-vivo structure analysis. In: Non invasive methods and the skin (Serup and Jemec Edrs.), CRC Press !ne., Bocaraton, Florida, p. 257 11. Cardillo A., Morganti P. (1994), A fast non-invasive method for skin hydration contro!, J. Appl.Cosmetol. 5, 105-120 12. Webb S. (1990), "The Physics of medicai imaging", Ed. Adam Hilger, Bristol. 13. Edwards C. (1988), Non invasive in vivo measurement of dimensions and properties of stratum corneum and epidermis by A-Scan ultrasound, 15th IFCC /11tematio11al Congress 4, 263-4 14. Pugliese P.T. (1989), Use of ultrasound in evaluation of skin care products, Cosm. Toil. 104, 61-76 15. Armengol R., Girones E., Belles A. et al. (1992), Quantitative evaluation of the anti-cellulitis efficacy by scan-ultrasound and its relation with clinic studies, 17th IFCC lnt. Congr. Voi. 3, 1218- 1240 16. Fornage B.D. and Anderson M.D. (1995), Ultrasound examination of the skin and subcutaneous tissues at 7 .5 to I O MHz. In: Non-invasive methods and the skin (Serup and Jemec Eds.), CRC Press lnc., Bocaraton, Florida, p. 279 17. Agner T. (1995), Ultrasound A-mode measurement of skin thickness. In: Non-invasive methods and the skin (Serup and Jemec Eds.), CRC Press Inc., Bocaraton, Florida, p. 289 18. Morganti P. (1997), A new peloid mask of Etruscan origin. Presented at IN-COSMETICS Conference, Di.isseldorf, May 6. Published on the Conference Proceedings "Modem challenges to the Cosmetic Formulations", p.451-456, J. Appl.Cosmetol. 15, I 09 145 . ~" .... J. Appl. Cosmetol. 15. 147-159 (October-December 1997) ENHANCING THE GLYCOLIC ACID EFFICACY BY PIEZOELECTRIC VIBRATIONS P. Morgonti", S.D. Rondozzo•• ond G.Fobrizi*** • President/Director, R & D - Mavi Sud S.r.l., Viale dell'Industria l, 04011 Aprilia (LT), ltaly. Department of Dermatology, Dermatologists Training School, Il University of Naples, ltaly. •· Department of Dermatology - University of Catania, ltaly. ••• Department of Dermatology, Catholic University of Rome, ltaly. Received: May 7, 7997 Presented at 2sd Symposium on Cosmetic Efficacy, New York, 28-30 Aprii, 7997. Key words: Glycolic acid, Piezoelectric vibration, Skin sticity, Skin hydration, Surface lipids, TEWL. Maste~. Skin ageing, 3C System®, Skin ela- Synopsis As it is well known, AHAs improve skin hydration by binding water to the stratum corneum. In addition, when applied topically in concentration between 8% and 70% they decrease corneocyte cohesion and stratum corneum thickening, including various levels of epidermal separation. Among the various AHAs available, glycolic acid has enjoyed the greatest popularity. Its higher concentrations (from 50% to 70%) are being used for superficial skin peeling,meanwhile, iow concentrations (from 8% to 30%) have been reported to act as moisturizing agent capable of causing a decrease in corneocyte attachment. The glycolic acid activity is always correlated to some degree of irritation, and stinging or burning is its common side effect-especially at the begining of treatment. This study investigates and compares the effect of a 20% glycolic acid product, partialiy neutralized at 4,5 pH with a special blend of aminoacids, used as "lunch time peel" on skin degreased by a cleansing lotion combined with or without a new "piezoeiectric technology" called "Skin Master®". Skin Master® activity is based on mechanical energy trasmitted to the skin by a series of ultrasound vibrations. Through the Skin Master® device, a significant exfoliation of the horny layer is obtainable together with a contemporary micromassage of the skin with an evident hyperemia. In this way, it is possible to enhance the glycolic acid absorption and its activity at medium/low concentrations. In order to explore the activity of this 20% glycoiic acid-containing product and to verify the real use of the Skin Master®, Skin Elasticity (RER by Dermafiex®), Clinica! Scoring (CS) (according to Effendy et al.), Stratum Corneum Turnover Time (SCTT) by the Dansylchioride Methodology (Jansen at al.), TEWL, Superficial Skin Lipids and Skin Hydration were controlled by 3C System®Technology (Rome, ltaly) on 30 women aged 35-56 who were observed weekly for 3 months. No significant adverse reactions were noted during the 90-day study. The obtained results indicate a significant reduction (p<0.005) of SCTT (+ 20%), substantial modification of TEWL, and an increase of superficial skin lipids ( + 27% ), skin hydration ( +70%) and skin eiasticity (+ 12%). These benefits were significantly (p<0.05) improved (+ 25%) when the Skin Master® was used. 147 Enhancing the glycoilc acid efficacy by piezoelectnc vibrat1ons Riassunto Come è noto gli alfaidrossiacidi aumentano l'idratazione cutanea legando l'acqua allo strato corneo. Inoltre, quando sono applicati topicamente in concentrazioni tra 1'8% ed il 70% fanno diminuire la coesione dei corneociti e l'inspessimento dello strato corneo, accelerando a vari livelli la div isione cutanea. Tra i vari AHA disponibili, l'acido glicolico è quello che gode della più grande popolarità. Le sue alte concentrazioni (dal 50% al 70%) sono utilizzate per il peeling cutaneo superficiale, mentre le basse concentrazioni (dall '8% al 30%) sono risultate agenti idratanti in grado di causare anche una diminuzione nella coesione dei corneociti . L'attività dell'acido glicolico è sempre correlata a qualche tipo di irritazione, ed il prurito e l'arrossamento ne sono comuni effetti collaterali, soprattutto all'inizio del trattamento. Con questo lavoro si sono voluti valutare gli effetti di un prodotto contenente una percentuale del 20% di acido glicolico, parzialmente neutralizzato ad un pH 4,5 tramite una speciale miscela di am inoacidi. Il prodotto viene utilizzato come "lunch time peel" sulla pelle precedentemente detersa con una lozione detergente, in combinazione o no con la nuova tecnologia piezoelettrica denominata "Skin Master®". L'attività dello Skin Master®è basata sulla energia meccanica trasmessa alla pelle da una serie di vibrazioni ad ultrasuoni. Con l'uso dello Skin Master® si ottiene una significativa esfoliazione dello strato corneo, insieme ad un contemporaneo micromassaggio della pelle con evidente iperemia. In questo modo è possibile aumentare l'assorbimento dell'acido glicolico e la sua attività a concentrazioni medio I basse. Per analizzare l'attività di questo prodotto e per verificare il reale uso dello Skin Master0 , sono state controllate settimanalmente e per tre mesi 30 donne di età compresa tra i 35 e i 56 anni con la tecnologia del 3C System® (Rome, Italy). I valori controllati riguardavano l'elasticità della pelle (RER Derrnaflex®), il grado di eritema della cute (Clinica! Scoring - CS secondo Effendy et al. ), il rinnovo delle cellule cutanee, Stratum Corneum Turnover Time (SCTT) con la Dansylchloride Methodology (Jansen et al.), la TEWL, i lipidi cutanei di superficie e l' idratazione della pelle. Durante la durata dello studio (90 giorni) non sono stati riscontrati significativi effetti collaterali. I risultati ottenuti indicano una riduzione significativa (p<0.005) dello SCTT (+ 20%), una modifica sostanziale della TEWL, ed un aumento dei lipidi cutanei di superficie (+27%), dell'idratazione cutanea (+70%) e dell'elasticità della pelle (+12%). La positività dei dati è risultata significativamente più elevata (+ 25% p<0.05) nelle aree trattate con lo Skin Master®. 148 P Morgant1, S.O Randazzo, G.Fabriz1 As it is well known AHAs improve skin hydration and photo-induced skin ageing by binding of water to the stratum corneum ( 1-1 7). In addition, when applied topically in concentration between 8 and 70% they decrease corneo c y te cohesion and s tratum corneum thickenig, including various levels of epidermal separation, Among the various AHAs available, glycolic acid has enjoyed the greates t popularity, Its high er concentration s (from 50 to 70%) are beeing used for superficial skin peeling meanwhile low concentrations (from 8 to 30 %) have been reported to act as moisturizer agent capable also to cause a decrease in corneocyte attachment (18-21). The glycolic acid activity is always correlated to some degree of irritation and stinging or burning is its common side effect, especially at the beginning of treatment (22), These side effects are linked to its own irritant properties as acid, but are also based on the following factors: concentration, pH, percentage and type of neutralizers used to adjust acidity, vehicle form ul ation, cleaning and/or degreasing treatment used, period of time the acid remains on the skin, skin area and skin type (23). Because of glycolic acid known ability to be effective on some photodamage, pigmentation, scarring condition and fine wrinkles improvement, physicians and aestheticians are using it primarily in high/medium concentrations, For these reasons the use as "refresher peel" of a glycolic acid solution at medium degree concentration of simpler use should be interesting fot both the medicai community and aestheticians, particularly if without side effects. This study investigates and compares the effect of a 20% glycolic acid-peel, partially neutralized at 4.5 pH with a special blend of aminoacids (*), used as "lunch time peel", on skin degreased by a cleansing lotion or by a new "piezoelectric technology" called Skin Master"'. STUDY PROJECT In order to verify the real use of th e Skin Master® and to explore the activity of this 20% glycolic acid-peel, Stratum Corneum Tumover Time (SCTT). Skin elasticity, Clinica! scoring and TEWL were controlled on upper forearm; Skin lipids and Hydration were controlled on the face. Skin Master8 3C Systerrf' CHEMICALS Gel A: water gel of glycolic acid 20% (lml = g 0,224 of GA) partially neutralized by Na OH (pH 4.5) GA. GelB: water gel of glycolic acid 20% (lml = g 0,224 of GA) partially neutralized by aminoacids (pH 4.5) GA-Arg/Gly (*). (*) Trade nome: Keratotal"' Peel 149 Enhancmg the glyco/1c ac1d eff1cacv by p1ezoelectnc v1brat1ons Cleansing Lotion: (pH 4.5) Aqua, Ceteareth-6, Isopropyl myristate, Octyl steara te , Lactic acid , Sorbito!, Propylene glycol, Glycerin, Gelatin-Glycine(IJ, Hydrolyzed collagen, Tocophery I ace tate, Retinyl palmitate, Linoleic acid, Linolenic acid, Disodium EDTA, Imidazolidinyl urea, Methylparaben, Parfum (*). TEST PROCEDURE ON THE FACE Patients Skin Master®'s activity is based on mechanical energy transmitted to the skin by a series of ultrasound vibrations of its special actuator. The extreme part of the actuator, induced to vibrate by piezoeletric device, produces compression and decompression on the skin surface. The outcome of this treatment is a smooth relaxed and cleaned skin and toned musculature. Fourthy healthy women volunteers, age range 35 to 56, skin type III/IV, part!cipated in the study. Each woman had at least a moderate degree of photodamage as defined by an overall score of 5 with separate scores for each side of the face on a visual analogue scale of O (none) to 10 (severe). The number of actinic keratoses and wrinkling improvement were also counted. No topica! retinoid use or other topica! medications or cosmetic antiaging products were allowed for 1 month prior to study initiation. The subjects were observed daily or weekly for three months (January-March) always by the same investigator. Patients were randomly divided into four treatment groups of 1O individuals. After baseline evaluation, one group was treated twice a week by a 20% glycolic acid "refresher peel" (partially neutralized by aminoacids at pH 4.5) (Gel B) for 2 months, after cleansing the face with a Cleansing Lotion (TS Gentle Cleansing) (Group 1). The second group was treated with the same peel, after cleansing the skin, previously wetted with distilled water, by using the Skin Master® (Group 2). The thirth and the fourth group were respectively treated as the first and the second but used also a phospholipid-based moisturizing lotion twice daily. 3C System® Procedure This computerized system through the capacitative resistance permits a simple and quick contro! of surface lipids, skin hydration and TEWL. The 3C System"' collects up to 10/15 measurements over 25 seconds sampling period and records the mean value automatically standardizing the environmental conditions (RH=50%, T=22°C) (11). To perform the peel the following procedure was utilized: the Gel B (glycolic acid peel) was applied uniformly over the entire face after the skin was cleansed with Gentle Cleansing or Skin Master®. Application times were started at 15 minutes for each peel treatment. Gel-Vehicle: water, propylene glycol, xantan gum (pH 4.5). Moisturizing Lotion: Soybean liposome containing l 0% lecithin frac ti on with 80% phosphatidylcholine linoleic acid-rich. Skin Master® Technical specifications Actuator frequency: 25.000 Hz+/- 10% Vibration at time actuator: 30 micron pp Frequency: O.I - IOOOHz Work cycle: 5 sec. Maximum of current: 10-600 microA (*) Trade nome: TS Gentle C/eansing 150 (1) USA patented n °4806525/ Feb.2, 7989 P Morgont1. S D. Rondozzo. G.Fobnz1 SKIN FACE HYDRATION OF PATIENTS TREATED BY A 20% GLYCOLIC ACID·PEEL PARTIALLY NEUTRALIZED BY AMINOACIDS·ARG/GLY AT pH 4.5 n = 40 • RH = 50% • t = 22 ·e 100 80 w cn < w 60 a: 40 ~ 20 ~ w cn < w ~ / o ·20 - / ~ ~ ~ ~ ~ ~ I-- Sili - ~ - ~ f- :I ~ldl ~ ~ - - a: ow e ~ -60 ·80 -100 15 ~ 30 CL+GA+M ~ - 60 45 ~ SM+GA+M CL+GA 75 ~ SM+GA 90 I DAYS Treatment period: 2 Months (Twice a Week) with and without using a molsturizlng lotlon (Twice a Day) All p values are highly s ignificant (p < 0.005) as to Baseline Fig. I Abbreviations: CL=Cleansing Lotion, GA=Glycolic Acid, M=Moisturizing Lotion, SM=Skin Master SKIN FACE LIPIDS OF PATIENTS TREATED BY A 20% GLYCOLIC ACID·PEEL (PARTIALLY NEUTRALIZED BY AMINOACIDS·ARG/GLY AT pH 4 ,5) ANO BY MOISTURIZING CREAM (TWICE A DAY) n =40 • RH = 50% -t= 22 •e w ~ w a: o ~ 15 + - - - ----11--:.,,c-- - - + - -- - + -- - = 10 +-------lf------+''-"';""'""'--~ 11.1:t1 ~ O +------l-----+----+------11-------+----~ o 15 I• 30 SM+GA • 45 CL+GA A 60 CL+GA+M • 75 90 DAYS SM+GA+M Peel-Treatment period: 2 Month (Twice a Week) with and without a moisturizing lotion (Twice a Day) All p value are highly significant (p < 0.005) as to Baseline and Groups Fig. 2 Abbreviations: CL=Cleansing Lotion, GA=Glycolic Acid, M=Moisturizing Lotion, SM=Skin Master 151 Enhancmg the glycollc ac1d eff1cacy by p1ezoelectnc v1brat1ons SKIN FACE CLINICAL SCORE ASSESSMENTS AT WEEK 12 OF PATIENTS TREATED (TWICE A WEEK) BY A 20% GLYCOLIC ACID·PEEL PARTIALLY NEUTRALIZED BY AMINOACID-ARG/GL Y n = 40 • RH = 50% • I = 22 ' C FINE WRINKLING AROUND EYES 6 CREASE LINES AROUNO MOUTH AND CHEEKS 5 4 3 2 o SM + GA CL+ GA SM+GA+M CL+GA+M ~ Baseline Before ~ After al Week 12 SM+ CL+ GA·GLY/ARG GA·GLY/ARG ~ Baseline Before SM+GA ·GLY/ARG +M GA·GLY/ ARG +M [ill After al Week 12 All p values are highly significant (p < 0.005) as to Baseline and to Groups Peel-Treatment perio d: 3 months (Twice a Week) wlth and w lthout using a moi sturlzing lotlon (Twlce a Day) Fig. 3 Abbreviations: CL =Cleansing Lotion, GA=Glycolic Acid, M=Moisturizing Lotion , SM=Skin Master Every two weeks at I 0.00 a.m. surface lipids, sk.in hydration, the number of crease lines and the degree of wrinkling improvement were controlled. Tue obtained results are reported in Fig l ,2,3. TEST PROCEDURE ON THE FOREARM Strafum corneum turnover time (SCm Tue right or left foream1 was marked with 7 areas of 2cm2 each, treated in this way: AREA I Cleansed with Cleansing Lotion AREA 2 Skin Master AREA 3 AREA 4 AREA 5 Cleansing Lotion Skin Master AREA 6 + Gel A + vehicle Gel +Gel A + vehicle Gel +Gel B +Gel B AREA 7 UNTREATED 152 Areas treated by S kin Maste r* were previously we tted with distill ed water. Prior to treatme nt the stratum corne um was labelled with dansyl c hloride according to Jansen et al. (24) methodology. According to Effendy et al. (25) dansyl chloride was finely triturated into white petrolatum at 5% (w/w) and applied to right volar fo rearm of the volunteers under semi-occlusive dressing for 24 h. Subseque ntly, after remove of a ny excess materiai with soft tiss ue pa pe r, and afte r c leansing the a rea by cleansing lotion or by Sk.in Master*, test substances were applied. The clearance of the fluorescence was exami ned under UV illumination. SCTT was the time in days be tween staining (day 0) and fluorescence disappearance. O, l ml. of g lycolic acid-Gel-B (pH 4.5), g lycoli c acid-Gel-A (pH 4 .5) and ve hic le ( pH 4.5) were applied respecti vely to the d ansyl c hl oride-labelled areas pre-treated by C leans ing Lo tion or S kin Maste r4'> volar fo rearm a reas using p olypropyle ne cha mbers ( 19 mm P Morganti. S D. Randazzo, G.Fabnzi STRATUM CORNEUM TURNOVER TIME (SCTT) ANO SCTT 50 OF FOREARM SKIN TREATED BY A 20% GLYCOLIC ACID-PEEL PARTIALLY NEUTRALIZED BY NaOH OR AMINOACID-ARG/GLY (pH 4,5) n = 40 - RH = 50% - t = 22 SM + GA +NaOH SM+GA -GL Y/ARG CL + GA -NaOH ID CL+GA -GL Y/ARG SCTT 50 • •e SM+ VEHICLE SCTT CL+ VEHICLE CONTROL UNTRATED I Ali p values are highly significant (p < 0.005) as to Control values and Groups Fig. 4 Abbreviations: CL=Cleansing Lotion, GA=Glycolic Acid, M=Moisturizing Lotion, SM=Skin Master ERYTEMA/SCALING SCORE OF FOREARM-SKIN TREATED BY A 20% GLYCOLIC ACID.PEEL PARTIALLY NEUTRALIZED BY NaOH OR AMINOACID-ARG/GLY n 3,0 = - RH =50% - T =22 ·e - pH =4,5 ~----~------r-----~-----.,.--------, 10 5 • SM+GA-NaHO (Gel A) .6 CL+GA-NaHO (Gel A) e 15 SM+GA-ARG/GLY (Gel B) + CL+GA-ARG/GL Y (Gel B) * 25 20 TIME (Days) SM+VEHICLE X CL+VEHICLE Ali p values are highly significant (p < 0.005) as to Baseline and Groups Fig. 5 Abbreviations: CL=Cleansing Lotion, GA=Glycolic Acid, M=Moisturizing Lotion, SM=Skin Master 153 Enhonc1ng the glycot1c ac1d ett1cocy by p1ezoelectnc v1brot1ons SCALING: O = no scale I minimal, fi ne 2 moderate 3 Jarge flakes, intense peeling di ameter) on paper adhesive tape for 15 min. Once daily (5 consecutive days for 2 weeks) according to the metho~ described by Effendy et al. Chambers with an erythema score of 3.0 or greater were not reapplied. Vehicle Gel served as contro!. Untreated skin served as a contro! site. The obtained results are reported in Fig. 4 and 5. Skin elasticity Skin elasticity has been controlled weekly I Oa.m. to ali patients on a marked forearm area by Dermaflex" A( (Cortex Technology, Hadsund, Denmark) (26). Tue evaluation of the skin was determined electronically by measuring electric capacitance between the marked skin surface and the electrode placed in the top of the suction chan1ber. The parameters used were: suction 450m bar, suction period 20s, number of cycles 5. The obtained results are reported in Fig. 6 and 7. ERYTHEMA SCALING SCORES Each test site was always examined and graded for erythema and scaling according to: ERYTHEMA: O = no erythema 0.5 = I = 2 = 3 = 4 = equivocai reaction slight erythema moderate, uniform erythema intense fiery redness with edema DISTENSIBILITY OF FOREARM-SKIN TREATED BY A 20% GLYCOLIC ACID.PEEL PARTIALLY NEUTRALIZED BY NaOH OR AMINOACID-ARG/GLY (pH 4.5) n = 40 - RH = 50% - t = 22 •e 6 . / 5 4 4.4 ±0.3 ,,. - :::::::::;: 4.5± 0.2 e=- 4 .6 ± 0.3 4 .6± 0.4 ::::=- ~ ~ - - ; 3 v- 2 v- '--- ' ' vo ' '·• - ' CL + GA-NaOH ~ .' ; CL+ GA-Gl Y/ARG li -- - SM + GA·NaOH - - - - - SM+ GA-OLY/ARG .::::::::;; - 1 ., 4 .3 :t0.4 4 .2± 0.3 '"---- .- : SM+ VEHICLE L- : -..... CONTROL UNTRATED All p value are NOT significant as to Untreated Contro! and Groups Fig. 6 154 Abbreviations: C L=Cleansing Lotion, GA=Glycolic Acid, M=Moisturizing Lotion, SM=Skin Master P Morgant1. S D. Randazzo. G Fabrw RELATIVE ELASTIC RETRACTION (RER) OF FOREARM-SKIN TREATED BY A 20% GLYCOLIC ACID-PEEL PARTIALLY NEUTRALIZED BY NaOH OR AMINOACID ARG/GLY (pH 4,5) n = 40 • RH = 50% • t = 22 ·e 9 O/ 80 V 7o v 60 50 88 j 0.93 84± 0.91 ~~ A AA 75 ± 0.90 72±0.87 ~ 65 ± 0.95 v- "' f--- - /- ~ 40 ,..'-- 30 ,..'-- - 20 ,..- - 10 o ~ (/~ = ....,..,_ CONTROL UNTRATED SM + VEHICLE ..__,:-;:-:I I CL + GA·NaOH SM + GA·NaOH I ~.,., CL + GA·GLY/ARG ~ SM + GA· GLY/ARG All p values are highly significant (p < 0.005) as to Untreated and Groups Fig. 7 Abbreviations: CL=Cleansing Lo1ion, GA=Glycolic Acid, M=Moisturizing Lotion, SM=Skin Mas1er TEWL, SUPERFICIAL SKIN LIPIOS ANO SKIN HYORATION RESULTS ANO OISCUSSION Eryfhema and Scaling TEWL, skin Jipids and hydration were controlJed weekly on the skin face by the 3C System"' methodology (Dermotec, Rome, Italy) (27). Thi s computerized system permi ts a simple and quick determination of TEWL, superficial ski n lipids, hydration and pH, whi le the environmental conditions are automatically standard ized (50% RH and 22°C) by the use of proper correction factors. TEWL is expressed as the amount of water evaporated per unit of su rface in 1 hour gr/m2/h and the system collects up 10/ 15 measurements over 25 second sampling period and record the mean value automatically. The obtained results are reported in F ig. 1, 2 and 8. As expected the Gel A application (20% glycolic acid partially neutralized by NaOH at pH 4.5), compared to its vehicle (p<0.005), caused a strong erythema (2nd degree) from the second day of treatment on the cutaneous area already cleansed with cleansing lotion. This erythema turned out even stronger when the cleansing was carried out by us ing Skin Master"' (3 degree), that, as expected, allowed the glycolic acid to pass through the cutaneous Iayers even quicker. The Gel B application (20% glycolic acid partially neutralized at pH 4.5 by aminoacids) has recorded, on the contrary, only a slight erythema fro m day 8 to day I O as compared to its vehicle 155 Enhoncing the glycolic oc1d eff1cocv by piezoelectr1c v1brot1ons TRANSEPIDERMAL WATER LOSS OF FOREARM·SKIN TREATED BY A 20% GLYCOLIC ACID·PEEL PARTIALLY NEUTRALIZED BY NaOH OR AMINOACID-ARG/GLY (pH 4,5) n =40 • RH = 50% • t = 22 •e ~:-,~~~~e::==:==~ ===~F==: 2+-~~~-+-~~~-+-~~~-+-~~~-+-~~~--+-~~~-< o 2 10 5 15 • SM+GA-NaOH e .6. CL+GA-NaOH + CL+GA-ARG/GLY SM+GA·ARG/GLY * 20 25 DAYS SM+VEHICLE X CL+VEHICLE All p values are highly significant (p < 0.005) as to Vehicle and to Groups Fig. 8 Abbreviatio11s: CL=Cleansing Lotion, GA=Glycolic Acid, M=Moisturizing Lotion, SM=Skin Master (p< 0.005), and produced evident scaling from day 1O to day 18. This did not occur with the vehicle (Fig. 5). TEWL In accordance with Effendy et al. TEWL at the GA-treated area increased on day 10 and maintained significantly hi gher levels than the untreated or vehicle-treated skin (p<0.005). Only the areas treated with g lycolic acid partiall y neutralized with ARG/GLY aminoacids showed TEWL levels similar to the vehicle. These levels were higher only when the skin was pre-treated by Skin Master®, and when glycolic acid (GA) partially neutralized with NaOH was used, implying that the water barrier of Stratum Comeum is altered by the glycolic acid treatment more or less clearly not only in relation to the quantity of free glycolic acid, but also to the kind of used neutralizer and to the intensity of the cleansing treatment used. What seems even more 156 interesting is the fact that the alterati on of the barrier seems not to be dependent from the pH, as often asserted by different authors (15,19, 2122), but from the kind of neutralizer used (Fig. 8). The glycolic acid used, neutralized by a mix.ture of aminoacids, acted in a way fairly similar to the vehicle (Fig. 8), unlike the same glycolic acid neutralized by NaOH. SCTT G lycolic ac id has significantly reduced SCTT and SCTT-50 with respect to the veh icle and the contro! (Fig. 4), both when partially neutralized with NaOH ( 14.0±7, p<0.005) and by aminoac ids ( 14.0±1, p<0.005)), after cleansi ng previously the skin with C leansi ng Lotion. The use of the Skin Master®has furtherly reduced the SCTT (GA-Arg-Gly 13. 1±0.9 and GA-Na OH 12.9±0.9) (p<0.005), proving that this type of cleansing helps the absorption and therefore the activ ity of glycol ic ac id and of P. Morganti, S.D Randazzo, G.Fabriz1 active ingredients in generai. These results prove, as already ver ified by ourselves and other authors, that glycolic acid acts as Stratum Corneum cel I renewal accelerator, and that the inten s ity of activ ity a nd the the erythema degree is strictly related also to the means of cleansing used and to the used chemical neutralizers (Fig. 4 and 5). It seems not to depend, therefore, only on the free glycolic ac id. Superficial skin lipids, hydration and e/asticity As it is known and as can be seen the everytwo-week treatment with glycolic acid, considerably improves the skin elasticity (RER) (Fig. 7) (pH<0.005 with regard to contrai), but not the skin distensibility (Fig. 6). Concerning hydration and surface lipids (Fig. I and 2) it is evident that the peeling reduces the skin hydration and seems to have an influence a lso on superficial skin lipids thanks to the exfoliating activity ca used by g lycolic acid if used in 20% concentrations without the use of emollients. When the treatment is integrated by the use twice a day of an emollient cream results invert. CONCLUSION As already supported by several authors g lycolic acid carries out an interesting biologica! activity, w hi ch is not completely explained yet. From these first data, however, it seems possible to say that it obtainable an interesting increase of celi turnover by using lighter and simpler peeling, that can be performed also by expert aestheticians. It is of extreme importance to perform before the treatments a careful cleansing. and it is fundamental not only the product's pH and the neutralizing degree, but the kind of neu tralizer used, that affects also the erythemigenic components and the stinging activity carried out by this AHA. It is also fundamental the use of moisturizing c reams after the peeling treatments, in ordcr to improve the appearance of photoaged sk in by reducing fine wrinkling and crease lines and to en hance the radiance of the skin giving complexion a fresh, youthfu l glow. Finally, we found highly interesting the use of the Skin Maste~ as new cleansing means, to be used to deeper cleanse the ski n when there is a need to accele rate and improve the absorption and the activity of AHAs or other cosmetic active ingredients. Aufhor Address: Clinica/ score assessmenf Before (Day O) and after 12 weeks of treatment clinica( score assessment was checked by the same dermatologist for all patie nts GA-treated (p<0.005). The individuai signs of fine wrinkling around eyes and crease lines around mouth and cheeks were scored on 0-10 visual analogue scales with separate scores for each side of the face. The patients treated also w ith the post-peel moisturizing cream (twice a day)and pre-treated by Skin Master~ demonstrated the highest improvement on wrinkling and crease lines also at week 4 and 8 (p<0.05) in respect to other groups (Fig. 3). P. Mmga11ti, PhD - Research and Development MAVI Sud srl - Via del!' Industria 1, 04011 Aprilia (LT), JTALY Phone: + 39 06 9286261 Fax:+ 39 06 9281523 E-maiI=mavi@colosseum .iI URL=h1tp ://www.colosseum .itlst81 Ima vi 157 Enhoncing file glycolic oc1d eff1cocv by p1ezoelectnc vibrot1ons REFERENCES 1. Van Scott EJ, Yu RJ. (1974), Control of keratinization with alpha hydroxy acids and related compounds: l .topical treatment of ichtyotic disorders, Arch.Dermarol. 110, 586-590. 2. Van Scott EJ, Yu RJ. (1984), Substances that modify the stratum comeum by modulating its formation. In: Principles of Cosmetics for the Dermatologists. (Frost, SN Horwitz, eds.) CV Mosby Co., St. Louis, p.70-74 3. Van Scott EJ. (1988), The unfolding therapeutic uses of alpha hydroxy acids, Med guide to Dermatol., 3, 1-5. 4. Van Scott EJ, Yu RJ. (1989), Alpha hydroxy acids: therapeutic potentials, Canadian f. Dermatol. 1, 108-112. 5. Dahl MV, Dahl AC. (1983), 12% lactate Iotion for the treatment of xerosis, Arch Dermatol. 119, 27-30. 6. Buxman M, Hickman J, Ragsdale W, et al. (1986), Therapeutic activity of lactate 12% lotion in the treatment of ichthyosis. Active vehicle and active vs. a petroleum cream, f. Am. Acad. Dermatol.15, 1253-1258. 7. Van Scott EJ, Yu RJ. (1989), Alpha hydroxy acids: treatment of the Aging Skin with Glycolic Acid procedures for use in clinica] practice, Cutis. 43, 122-128. 8. Moy LS. (1990), The use of gJycolic acids in the treatment of various skin disorders. Communication at the l 7th Annua! Clinica! and Scientific Meeting of the American Society for Dermatologie Surgery. Reported in Canadian Medicai News, July 27. 9. Dial W.F. (1990), Preparations prescribed in anti-wrinkling therapy, Cosmet Dermatol. 3, 32-34 10. Ridge J.M., Siegle R.J., Zuckerman J. (1990), Use of alpha hydroxy acids in therapy for photoaged skin, J. Am. Acad. Dermatol. 23, 932 11. Hermitte R. (1992), Aged skin, retinoids and alpha hydroxy acids, Cosmet. Toilet. 107, 63-66 12. Vilaplana J. (1992), Clinica! and non-invasive evaluation of 12% ammonium lactate emulsion for the treatment of dry skin in atopic and non-atopic Subjects, Acta Dermatol. Venero/. 72, 28-33 13. Wehr F.R. (1991), A controlled comparative efficacy study of 5% ammonium lactate lotion vs. an emollient control lotion in treatment moderate xerosis, J Am. Acad. Dermatol. 25, 849-851 14. Morganti P., Persechino S. and Bruno C. (1994), Effects of topica! AHAs on skin xerosis, J.Appl. Cosmerol. 12, 85-90 15. Smith W.P., Smith W. (1994), Hydroxy acids and skin aging, Cosmet. Toilet. 109 (9), 41-48. 16. Morganti P., Randazzo S.D., Bruno C. (1996), AJpha hydroxy acids in the cosmetic treatment of photo-induced skin aging, J.Appl. Cosmetol. 13, 1 17 Morganti P., Bruno C. and Randazzo Sd (1997), Stratum comeum turnover time in aged skin, Cosmet. & Toilet 112, July, 61 18. Moy L.S., Murad H., Moy R.L. (1993), Glycolic acids peels for the treatment of wrinkles and photoaging, J.Dermatol. Surg-Oncol. 19 (3), 243-6 19. Di Nardo J.C., Grove G.L.,Moy L.S. (1996), Clinica! and histological effects of glycolic acid at different concentrations and Ph levels, Dermatol. Surg. 22 (5), 421-4 20. Clark C.P. (1996), Alphahydroxy acids in skin care, Clin.Plast.Surg. 23 (1), 49-56 21. Becker F.F., Langford F.P.,Rubin M.G. Speelman P. (1996), A hystological comparison of 50% and 70% glycolic acid peels using solutions with various pH, Dermatol.Surg. 22 (5), 463-5 22. Harris D.R. (1994), Treatment of the aging skin with glycolic acid. In: Evaluation and treatment of the aging face (Elson Ed.) Springer-Verlag, New York, p.26 158 P. Morganti. S.D Randazzo. G.Fabr/ZI 23. Brody H.J., Hailey C.W. (1986), Medium depth chemical peeling of the skin: a variation of superficial chemosurgery,J.Dermatol. Surg. Onco!. 72, 1268-75 24. Jansen L.H., Hojyo-Tomoko M.T., Kligman A.M. (1974), Improved fluorescence staining technique for estimating tumover of the human stratum corneum, Br.J.Dermatol. 90, 9-12 25. Effendy I., Kwangsukstith C., Lee J.Y. and Maibach H.I. (1995), Functional changes in human stratum corneum induced by topica! glycolic acid: comparison with ali-trans Retinoic Acid, Acta Derm. Venereo!. (Stochk) 75, 455-458 26. Elsner P.E. (1995), Skin elasticity. In: Bioengineering of the skin: methods and instrumentation. (Beradesca et al. Eds) CRC Boca Raton, USA p.58 27. Cardillo A., Morganti P. (1994), A fast, non invasive method for skin hydration contro!, J.Appl. Cosmetol. 12, 11 28. Morganti P., Fabrizi G. Randazzo S.D. and Bruno C. (1996), Decreasing the stinging capacity and improving the antiaging activity of AHAs, J.Appl.Cosmetol. 14, 79-91 159 Notes 1997 AWARDS 1997 can be considered particularly successful by Pierfrancesco Morganti, Ph.D., Editor in Chief of our Joumal. Dr. Morganti, Jeading an outstanding team of cosmetic and pharmaceutical scientists, accepted two coveted awards during this year. Their work, "The transdermal cosmetic delivery system: a new cosmeceutical device" was awarded "The Elegance Engineering Innovation Award" by Cosmetics & Toiletries magazine. This award was announced and publicly presented to Dr. Morganti during the I 997 Advanced Technology Conference in Dusseldorf, Gennany on May 3, I 997. The European Academy of Dermatology and Yenereology (E.A.D.Y.) Poster Prize was awarded and presented to Dr. Morganti by Prof. W.J.Cunliffe during the 6° E.A.D.Y. Congress in Dublin, lreland on September 15, 1997. The title of the poster was "A new cosmeceutical far all year round acne therapy". Congratulation from the entire editoria! staff of the Joumal to the Secretary General of Intemational Society of Cosmetic Dermatoly far such outstanding success. This reflects well on both the Society and the Joumal. Many of our membership rnay have equally significant honors, and we wou ld be pleased to announce them here, also. Editoria! Staff of the Journal of Applied Cosmetology The Elegance Engineering lnnovation Award from Cosmetics & Toi/etries® magazine and >ponsorcd by Amcrchol Corp. D1: P.Morgami receiving his Award from TJ.Malafronte President of Amerchol 160 BookRev1ew MECHANISM OF TRANSDERMAL DRUG DELIVERY Drug and Pharmaceutical Sciences. Series/8 Russel O. Pohs and Richard H. Guy Editors Published by Marce/ Dekker, New York - 376 hard bound, il/ustrated ISBN: 0-8247-9863-5 • US$ 750.00 Price subject to change without notice Marce! Dekker Inc., 270 Madison Avenue - New York, NY 10016-0602 This new book about transdermal delivery has surely hit the target, providing the readers with a fu ll survey of the mechanisms that are at the basis of Transdermal Delivery. This relatively new methodology was developed, as it is known, through three steps or generations, that gradually led to the realization of a better regulation, a better dosage and a better end-user comfort. The objective of the development was the improvement of the transfer and absorption mechanisms through the use of particular ingredients (or enhancers), the redacti on of the patch 's dimensions, the improvement of the outward appearance to the advantage of portability. This new book edited by Pohs and Guy in the "Drugs and Pharmaceutical Sciences" series of Marce! Dekker highlights "what is known", giving a "summary of what is happening now", together with "a perceptive look at what is to come in the area of mechanism and enhancement of molecular transport accross the stratum comeum" It begins by highlighting al i the most sophisticated technologies used to enhance the path ways of transdermal Stratum Comeum penetration including the usage of Penetration Enhancers, as new chemical molecules, of Orthophoresys and Sonophoresys, based on the use of ultrasonic energy. It is necessary to remind the reader that the need to stay in depth, improve and widen the knowledges and practical uses of drugs with controlled release arises from different requirements, and among those from the request of chemists of improving client's compliance towards the drugs (e.g. by decreasing the number of daily adm inistrations) and making more steady the hematic and topica! leve! of active ingredients. For these purposes patches are used to obtain a steady release of the drug in the space of a day or more, and an extreme user-friend ly product. Naturally, it is necessary to evalute the safety of this new device and to determine the degree of risk connected to its use. Ali the methodolog ies this interesting book deals with, those concerning the contro] of Stratum Corneum 's bilayers lipids, as well as those about th newest systems for the contro! of the drug release at cutaneous leve!, are described with plenty of detai ls and bibliographic notes. This book makes a useful reading for researchers who know the technological development wh ich patches have undergone in these last years, for graduates in medicine, biologists, pharmacists and students willing to learn the basis and the mechanisms of activity that regulate cutaneous absorption and the release of drugs and cosmetics through the organ skin. P. Morganfi, Ph.D Editor in Chief 161 lndex to Volume 15, 1997 lndex to Volume 15, 1997 Biologica! functions and therapeutic properties of urea. W. Raab Contents 115 Practical treatment of dry skin. Note W. Raab 125 1997 Awards 160 Book Review Originai Laboratory Studies Russe! O. Pohs and Richard H. Guy Editors An in vitro selection of new cosmetic active compounds: from screening tests on monolayered fibroblast culture to efficiency study on 3-D Derma! Equivalent. 161 C. Augustin, V. Frei. E. Perrier, A. Huc, O. Damour Mechanism of transdermal drug delivery, Drug and Pharmaceutical Sciences. Series/8 1 Generai Articles Demonstration of the anti-wrinkle efficacy of a cosmetic product. Correlation between clinica! observations and instrument methods. Skin care products and evaluation of few skin parameters: is the future already here? J.G. Camarasa, P. Anthoine, M.J. Tribo Boixareu, E. Serra M,G, Tucci, C. Zucchini, G, Ricotti, A Fionda, L. Morresi. 13 Baldrich. L. Aubert S. Scrrcsi, A. De Benediuis, G. Biagini 43 Effect of phosphatidylcholine linoleic acid-rich and glycolic acid in acne vulgaris. Contact allergy to preservatives and perfumed compounds used in skin care products. centi, L. Tiberi G. Angelini, G.A. Vena, C. Foti, M. Grandolfo 21 P. Morganti, S.D. Randazzo, A. Giardina, C. Bruno, M. Vin- 49 The use of a capacitance dev ice to evaluate the hydration of human skin. Role of topica! g lycolic acid and phosphatidylcholine linoleic acid-rich in the pathogenesis of acne. Linoleic acid versus squalene. V. Zuang, C. Rona, F. Distante, E. Berardesca P. Morganti, A. Agostini , C. Bruno, G . Fabrizi 95 33 A new peloid mask of etruscan origin. Hirsutism. Profile 011 Egyptian Females G. Fabrizi , P. Morganti H. M. El-Kahky, A. Imam, M. El-Okbi 109 59 162 lndex to Volume 15, 1997 Clinica] and instrumental evaluation of the activity of an anti-wrinkle cosmetic product on cutaneous relief and photoaged skin. E. Berardesca, F. Distante, P. Anthoine, G . Rabbiosi, L. Aubert 69 Topica! tretinoin for photoaging. The China experience. Xinghua Gao, Hong-Duo Chen, Albert M. Kligman 77 Human skin fibroblast culture to test glycolic and lactic acid solutions. M. Mattioli Belmonte, MG. Tucci , E . Vellucci, R. Solmi, G .Ricotti, O. Talassi, G. Biagini , P. Morganti 85 Clinica! evaluation of two baby wipes in a cross-over study. C. Feliciani , M. Di Carlantonio, R. Bellucci, M. Guarracino, P. Amerio 103 A comparative double - blind within subject study of the efficacy and tolerability of two different derivatives of Vitamin A on skin thickness and elasticity: retinoic acid and conjugated retinyl palmitate. E. Thom 133 A new cosmeceutical for the "orange peel" skin. P. Morganti, S .D. Randazzo, G.Fabrizi, C. Bruno 139 Enhancing the glycolic acid efficacy by piezoelectric vibrations. P. Morganti , S.D. Randazzo, G.Fabrizi 147 163 Author index Author lndex Agostini A., see Morganti P., 33 Amerio P., see Feliciani C., 103 Angelini G., Contact allergy to preservatives and perfumed compounds used in skin care products, 49 Anthoine P., see Camarasa J.G., 13; see Berardesca E., 69 Aubert L., see Camarasa J.G. , 13; see Berardesca E., 69 Augustin C., An in vitro selection of new cosmetic active compounds: from screening tests on monolayered fibroblast culture to efficiency study on 3-D Derma! Equivalent., 1 Bellucci R., see Feliciani C., 103 Berardesca E., Clinica! and instrumental evaluation of the activity of an anti-wrinkle cosmetic product on cutaneous relief and photoaged skin, 69; see Zuang V., 95 Biagini G., see Tucci M.G., 43; see Mattioli Belmonte M., 85 Bruno C., see Morganti P., 21; see Morganti P., 33 Camarasa J.G., Demonstration of the antiwrinkle efficacy of a cosmetic product. Correlation between clinica! observations and instrument methods, 13 Damour O., see Augustin C., 1 De Benedittis A., see Tucci M.G., 43 Di Carlantonio M., see Feliciani C., 103 Distante F., see Berardesca E., 69; see Zuang V., 95 El-Kahky H.M., Hirsutism. Profile on Egyptian Females, 59 EI-Okbi M., see El-Kahky H.M. 59 Fabrizi G., A new peloid mask of etruscan origin, 109; see Morganti P., 33; see Morganti P., 147; see Morganti P., 139 Feliciani C., Clinica! eval uation of two baby wipes in a cross-aver study, 103 Fionda A., see Tucci M.G., 43 Foti C., see Angelini G., 49 Frei V., see Augustin C., 1 164 Giardina A., see Morganti P., 21 Grandolfo M., see Angelini G., 49 Guarracino M., see Feliciani C., 103 Hong-Duo Chen, see Xinghua Gao, 77 Huc A., see Augustin C., 1 Imam A., see El-Kahky H.M. 59 Kligman A.M., see Xinghua Gao, 77 Mattioli Belmonte M., Human skin fibroblast culture to test glycolic and lactic acid solutions, 85 Morganti P., Effect of phosphatidylcholine linoleic acid-rich and glycolic acid in acne vulgaris, 21; Role of topi ca! glycolic acid and phosphatidylcholine linoleic acid-rich in the pathogenesis of acne. Linoleic acid versus squalene. 33; see Fabrizi G., 109; A new cosmeceutical far the "orange peel" skin, 139; Enhancing the glyco lic acid efficacy by piezoelectric vibrations, 147; see Mattioli Belmonte M., 85 Morresi L., see Tucci M.G., 43 Perrier E., see Augustin C., 1 Raab W., Biologica! functions and therapeutic properties of urea, 115; Practical treatment of dry skin, 125 Rabbiosi G., see Berardesca E., 69 Randazzo S.D., see Morganti P., 21; see Morganti P., 139; see Morganti P., 147 Ricotti G., see Tucci M.G., 43; see Mattioli Belmonte M., 85 Rona C., see Zuang V., 95 Serra Baldrich E., see Camarasa J.G., 13 Serresi S., see Tucci M.G., 43 Solmi R., see Mattioli Belmonte M., 85 Talassi O., see Mattioli Belmonte M., 85 Thom E., A comparative double - blind within subject study of the efficacy and tolerability of two different derivatives of Vitamin A on skin thickness and elasticity: retinoic acid and conjugated retinyl palmitate, 133 Tiberi L., see Morganti P., 21 Tribo Boixareu M.J., see Camarasa J.G., 13 Tucci M.G., Skin care products and evaluation of few skin parameters: is the future already here?, 43; see Mattioli Belmonte M., 85 Vellucci E., see Mattioli Belmonte M., 85 Vena G.A., see Angelini G., 49 Author index Vincenti M., see Morganti P., 21 Xinghua Gao, Topica! tretinoin for photoaging. The China experience, 77 Zuang V., The use of a capacitance device to evaluate the hydration of human skin, 95 Zucchini C., see Tucci M.G., 43 165 Sub1ect tndex Subject lndex 3C System®, 21, 24, 139; computerized system for measurements of skin parameters, 141 Acne, 21; and squalene, 36; papules, 26; pustoles, 26; and phosphatidylcholine, 27; and skin hydration, 29; and sebum secretion, 35; and hyperkeratosis, 35; and oleic acid, 35; and TEWL, 36; and linoleic acid, 36 Acne-affected skin, and squalene concentration, 38 Acne juvenilis, therapy by phosphatidylcholine cream, 35 Acylceramide, of comedones, 23 Age-spot, treatment of, 149 AHAs, 85 Alfa-amyl cinnamaldehyde, 51 Alphahydroxy acid, 85 Anthralin, and urea, 121 Anti-cellulitis, treatment by a natural mud, 111 Anti-wrinkle, efficacy, 13 Ascorbic acid, 4 Baby wipes, evaluation, 103 Benzalkonium chloride, 45 Benzylparaben, 54 Bifonazole, and urea, 122 Bioengineering instrument, 95 Biopeptides, 3 Biotechnology, 3; innovative, 1 Bronopol, 51 Butylhydroxyanisole, 51 Butylhydroxytoluene, 51 Butylparaben, 54 Cadmium chloride, 45 Capacitance, 95 Carbamide, 116; toxicity of, 116; moisturizing activity of, 116; biochemical functions of, 116; Keratolytic and desquamating activity of, 118; antimicrobial activity of, 121; in Dermatology, 121 Celi, proliferation, 3, 86; morphology, 89; contro! by SEM, 91 Cellulitis-patch, 140 Cellulitis, 109, 139; treated by a natural peat mud, 112 166 Ceramide-1, and linoleic acid, 23 China, photoaging in, 77 Chinese, 77 Chloracetamide, 51 Chlorexidine digluconate, 23, 35 Cholesterol, 110 Chondroltin-4-Sulphate, ~ Cinnamaldehyde, 51 Cinnamic alcohol, 51 Comedone, open and closed, 26 Contact allergy, 49 Contact dermatitis, and fragrances, 50; eyelids, 50; hands, legs and face, 50 Contrast microscopy, semiquantitative celi contro!, 89 Corinebacterium acnes, 35; count and phosphatidylcholine, 39 Corneometer®CM 820, 95 Corneosurfametry, and skin care products evaluation, 44 Cosmeceutical, a new, 21, 33; glycolic acid peel as, 147 Cosmetic, efficiency of, 1; moisturizing agent, 9 Cream, pH, 85 Cutaneous relief, 15 Dansylchloride, 147 Depilation, 60 Derma! equivalent, 3 Derma! matrix, 3 Dermoscan®C, 139 Diapers, 104 Dimethylthiazol diphenyltetrazolium bromide, 45 Dry skin, and urea, 121; significance of, 126; extemal causes of, 126; endogenous reason for, 126; regimen in, 127; cleansing measures in, 127; and environmental stress, 130 Dry-roughness, 77 Dyspigmentation, 77 EFA, deficiency, 35 Elastin, soluble fraction of, 4; synthesis, 7 Electrolysis, 66 Emulsion science, 3 Epidermal lipids, linoleic acid, 21 Epidermolysis, 86 Subject Jndex Epilation,60 Ergosterol, 110 Erythema, 154 Essential fatty acids, deficiency, 35 Ethylparaben, 54 Eugenol, 51 European Community, cosmetics directive of, 3; directive 93/35, 95 Extracellular Matrix, neosynthesis of, 6 Face, 77 Fibroblast, human, 4, 85; proliferation rate of, S, 14, 90; culture, 8, 86; morphology, 89; Formaldehyde, 51 Freeze fracture, 45 Geraniol, 51 Glucocorticoids, and urea, 121 Glycolic acid, 21, 85, 147; and phosphatidylcholine, 27, 33; and skin ageing, 147; 20% treatment, 147; and photodamage, 149; low concentration of, 149; increases skin elasticity, 155; reduction of SCIT by, 156 Glycosaminoglycans, 4; synthesis of, 5; realised, 6; electrophoresis of, 7 High-moor Peat, 109 Hirsutism, on egyptian females, 59; grading, 63; and electrolysis, 66 Hydroxycitronellal, 51 Hyperkeratosis, 35 Hyperkeratinization, provoved by FFA, 35 Image analysis, 18 Imidazolidinyl urea, 51 Interleukin-6, 45 Isoeugenol, 51 Isothiazolinones, 55 Kathon CG, 51 Keratinocytes, 3 Keratosis, 86 L-Glutamin, 3 Lactate dehydrogenase, 45 Lactic acid, 85 Laser, confocal scanning microscopy, 45 Lauryl sulphate, 45 Linoleic acid, cosmetic activity of, 21, 33; content in a natural mud, 111 Liposome,21,33,45;soybean,23; Magnetic resonance, 46 Mavigen, ldroschiuma, 24, 35 Melanocytes, 3 Methylparaben, 54 Milk, 3 Monolayered culture, 3 Mud, a natural ancient, 109; cosmetic use of a, 111 Natural Mud, 109 Oak moss, 51 Oleic acid, increase, 23 Orange-peel, skin, 139 Orthophoresys, 161 Parabens, 51 Patch, anti-cellulitis, 140 Peat Mud, 111; characteristics, 110; Ashes' analysis, 110; fatty acids content, 110, 111; sterol content, 111 Peloid, 109; peat etruscan mud, 109; Ashes' analysis, 110; fatty acid content, 110; sterol content, 111 Penetration Enhancers, 161 Phosphatidylcholine, 21; in acne therapy, 21, 33; and surface lipids, 27; and glycolic acid, 27; topica! activity, 28; and p.acnes counts, 39; cosmetic activity of, 21, 33 Photoaging, in Orientals, 79 Photodamage, 77; treatment of, 149 Pigmentation, treatment of, 149 Polydocanol, and urea, 122 Premature aging, 77 Preservatives, contact allergy to, 49 Proline, incorporation, 6 Propionibacterium acnes, 30 Propylparaben, 54 Quaternium 15, 51 Retin-A"', 77 Retinoic acid, 133 Retinyl palmitate, 133 Rheology, 3 Salicylic acid, 23, 35; and urea, 122 Sallowness, 77 Scintillation counter, 4 SCTT, 149 Sebum, linoleic acid concentration in, 21 Sitosterol, 111 Skin, reconstructed, 3; aged, 8; evaluation, 15; 167 Sub1ect lndex tolerability, 15; replica, 17; surface lipids, 24; free fatty acids/triglycerides ratio, 24; hydration, 25; surface, 26; topography, 44; equivalent, 44; fi broblasts, 45; photoaged, 69; roughness, 81; pH measurements, 106; microbiology evaluation, 107; hydratation, 128; thickness and elastic i ty, 135; thi ckn ess, 142; hydratation a nd TEWL, 143; ageing treatment, 147; elasticity, 154 Skin ageing, 147 Skin care, products evaluation, 43 Skin lipids, reduction of, 27 Skin Master~, 147 Sodium metabisulfite, 51 Sonophoresys, 161 Soya, 3 Stratum Corneum Turnover Time, 147 Squalene, increase, 23; concentration in acne, 38 TC DS, 139 TEWL, 35, 139, 149; measurements of acne affected patients, 36; skin, 143 Thymidine, tritiated, 88 Transderma l Cosmetic Delivery System, 141 Transdermal delivery, mechanism of, 161 Tretinoin, topica!, 77; and urea, 122 Triclosan, 51 Urea (carbamide), toxicity of, 116; moisturizing activity of, 116; biochemical functions of, 116; Keratolytic and desquamating activity of, 118; antimicrobial activity of, 121; in Dermatology, 121 Vitreoscilla filiformis, 70 Wa rts, 86 Wheat, 3 Wrinkle, depth, 17; treatment, 77 Wrinkles, 77 168 Announcement 6fh Congress of European Society tor Pediatrie Dermatology Rome, September 14-18,1999 Catholic University of Rome Auditorium of Congress Center This Scientific Congress has been organized by: "Centro Internazionale Studi e Ricerche in Dermatologia" "lslilufo di Oinica Dermatologica dell'Università Cattolica del Sacro Cuore" "Gruppo Italiano di Dermatologia Pediatrica"(GIDEP) under the patronage of: "Società Italiana di Dermatologia e Venereologia" (SIDEV) lf you wish to receive further information, please contact: G.Fabrizi, MD - lst. Clinica Dermatologica Univ. Cattolica del Sacro Cuore Tel./Fax: +39-6-30.13.250 Announcement Announcement Clinica/ Design Group /ne Seminar Series tor Medicai Devices BIOCOMPATIBILITY TESTING & MANAGEMENT: Material/Device biological safety January 73-74, 7998 •San Diego, CA GOOD MONITORING PRACTICES: lmplementing clinical trial January 75-76, 7998 •San Diego, CA CLINICAL' TRIALS DESIGN: Designing protocols and IDEs January 79-20, 7998 •San Diego, CA INTERNATIONAL CLINICAL TRIALS: Regulations from a round the world January 27-22, 7998 •San Diego, CA (STAY FOR THE SUPERBOWL!) sm • Regislration Fee: European venues up to 30 days before the event. S10901hereafter. VAT not applicable. Can't attend? &ly 1he book! $250 + shipping. Cali Nancy Stari< at Oinical Design Group lnc for catalog containing full course descriptions and registration information. 2 128 W Evergreen Ave Chicago, IL é/:XJ22 Phone: Fax: 773/489-5721 773/489-4281 Nof,'S ' Notes Notes Chiuso in tipografia: December 16, 1997 Journal of Applied Cosmecology published quarrerly by INTERNATIONAL EDIEMME, Via Innocenzo XI, 4 1 00165 Roma Icaly. Direccore responsabile: P. Morganci. Direzione, Redazione ed Amminiscrazione: Via Innocenzo Xl, 4 1 00165 Roma Iraly. Scampa: Grafica Flaminia, Roma. Impaginazione: GRAFO' Comunicazione visiva, Roma. Copercina: Dr.ssa M.G. Tucci - Dip. Ricerche INRCA -Ancona Iraly. ISSN 0392-8543 Spediz. Abb. Poscale 70% Filiale di Roma Auc. del Trib. di Roma n. 3 173/83 del 8-7-83. THE ANTIAGING LINE GLYCOLIC ACID ACTIVATED BY GELATIN - GLYCINE® TO NORMALIZE THE SKIN TURNOVER ~ ~~ - -; _:ì · ··~ LA LINEA ANTIAGING CON ACIDO GLICOLICO H ATTIVATO" PER NORMALIZZARE IL TURNOVER CUTANEO ~ L/Y.../Y_/. maVI La Ricerca Scientifica nella Dermocosmesi MAVI SUD s.r.l. Aprilia (LT) · ltoly THE EVOLUTION IN COSMETIC SCIENCE ACROMOS® DEPIGMENTANTE CUTANEO CON IDROCHINONE, ACIDO GLICOLICO E SCHERMO FISICO Primo del tra/lomento con Acromos Before the lrealmenl with Acromos Dopo l mese di troffo~enlo con Acromos Affer one mounth of lrealmenl with Acromos SKIN LIGHTNER WITH HYDROQUINONE, GLYCOLIC ACID AND NON·CHEMICAL UVA SCREEN Una risposta ottimale alle ipermelanosi cutanee Indicazioni: lpermelanosi acquisite di origine metabolica, endocrina, nutriziona le, chim ico-fisica, ecc. Modo d'uso: l-2 volte al dì per non meno di 8 settim ane ~ .L/Y...JY..J. mavt La Ricerca Scientifica nella Dermocosmesi MAVI SUD s.r.l. Aprilia ILT)-ltaly THE EVOLUTION IN COSMETIC SC/ENCE