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MAVIGRAPHICS by G . Fomiti
lV
From January 2008 the Journal of Applied Cosmetology changes the
lay out and the editorial content enriching its scientific purpose!
Attractive and healthy people are more privileged in life than unattractive
individuals. In fact health and beauty are the most popular top ics researched on the
internet and the term wellness has become synonymous of health, longevity and
young-Looking.
Thus a growing trend in the cosmetic andfood industry indicates that consumers are
demanding increasingly cosmeceuticals & nutraceuticals products able to promote
health, wellness and beauty.
On the other hand, to reduce premature or accelerated skin aging new medicai treatment modalities ha ve also emerged in order to allow the use of minimally
invasive and non-surgical approaches.
Therefore the development of different nove! types of lasers and other methodologies Leading to non-ablative and resurfacing skin rejuvenation, enabie plastic surgeons and dermatologists to offer new and innovative non-surgical treatments.
Because of the increasing of these new techniques in addition to the availability of innovative active cosmeceuticals as photoprotective agents also, the Board
of this journal decided to enlarge the professional scenario of the Applied
Cosmetoiogy giving room to diet suppiements and laser & medicai therapy for skin
health.
With the beginning of the new year we will add the word "skin health" to the
officiai logo of our journal.
Hence we will accept to receive scientifzc contribution from plastic surgeons also
and other experts invoived in preserving our wellbeing.
For practicai reason of reviewing the abbreviation of our journal in J. Appi.
Cosmetoi. will be maintained as such.
The Editor in Chief
P. Morganti
OIOQY
Trimestrale di Dermatologia Cosmetologica
Quarterly Review of Cosmetic Dermatology
EDITOR-IN-CHIEF
P. MORGANTI. Ph.0 .
EDITING ASSISTANT
Sccretary Generai
lntema1ional Society of Cosmctic Denna10Jogy
Via Innocen zo Xl. 41 • 00 165 Roma (ltaly)
E-mail:morganti ® iscd.i1
ASSOC IATE EDITORS
HONG-DUO CHEN, MD
Professor of Dcmiatology
No.I Hospital ofChina Medicai University
Shenyang 11000 1, China
E-mail : [email protected]
M.L. NUNZIATA
Via Innocenzo Xl. 41 • 00165 Roma (ltaly)
Fax +39-06-92.8 1.523
E-mail:in [email protected]
C. JACOBSON. M.D.
Past President - lnterna1ional Society of Cosmetic Dennatology
3600 Gaston Ave . Suite 1051 Dallas
TX 75246 USA
Fax + 1-214-8241900
SCfENTIFIC SECTIONS ANO EOITORIAL BOARO
Ccli and T issue Colture
G . Biagini (I)
L. Di Silvio (U K)
N. Stark (US A)
Molccular Biology
L. Bruckncr-Tudcrman (D)
V. Calabrese (I)
T. Kricg (D)
J . Uit10 (USA)
Skin Biology
B.Bcrra ( I)
M . Ponce (NL)
Photobiology
H. Honigsmann (A)
F.P.Noonan (USA)
Y.K.Park (Korca)
Skin lmmunology
A . Giannctli (I)
Skin Pcrmcation
J.P. Marty (F)
G. Puglisi (I)
Skin Pharmacology
F.H. Kcmper (D )
R. Paole t1i (I)
Skin Toxlcology
S. Paglial unga (()
M.G . Rozcn (USA)
Skin Ageing
Natural Cosmcsis and Balneology
G. Agostini (I)
B.R. Balda (D)
Non-Invasive Melhods and Biolechnologics
H. Tronnicr (D)
W. Gchring (D)
U. Hcinrich (D)
E. Berardesca (I)
P. Elsner (D)
Skin and Cosmetic Microbiology
J. Kabara (USA)
D.Orth (USA)
D. Stc inberg (USA)
Skin Bioenginccring
L. Andrcassi (I)
L. Rodrigues (P)
P. Elsncr (D)
Allergy Testing
F.K.E. Andersen (NL)
A. Scrtoli (I)
Chundi He (CHINA)
Cosmetic Manufacture and Co ntrol
L. Ntcta (SA)
A. Parsons (SA)
H.C. Roos (SA)
Cosmeti cs and Fragrances
G. Angol ini (l)
Cosmetics and Environment
Rctno l.S. Tranggono (Indonesia)
P. S uvanprakom (Thai land)
S. Jablonska (PL)
M. Noszczyk (PL)
M. Vcrschoore (F)
Aromatherapy and Natural Raw Materials
G . Salvatore (l)
Cosmetics ' Safety Evaluation
E. Chiacchcrini (()
Clinica! ln \'esligations
in Cosmelic Dermatology
H. Maibach (USA )
Xing-Hua Gao (CHI NA)
Hong-Duo Chcn (CHINA)
Ora! Mucosa and Dcntal Care Problems
E. Bcnagiano (I)
Naif Care Cosmetics
R. Baran (F)
B. Richcrt (B)
A. Tosti(I )
Hair Care Cosmetics
S. Calvicri (I)
W.A.D. Griffiths (UK)
C.E. Orfanos (D)
Cosmctics an d Skin Disorders
V. Mordovstev (R)
w. Raab (A)
T. Ruzicka (D)
Plaslic and Acsthetic S urgery
P. Palombo (I)
Cosm etic Pediatry
G. Fabrizi (I)
Y. Kazu ya (J)
A. Taieb (F)
Cosmetic Gynaecology
A. Lanzonc (()
S. Mancuso (I)
M . Massobrio (I)
J. Appl. Cosmetol. 25, 133-144 (October/December 2007)
SIRTl, THE HUMAN HOMOLOGUE OF THE YEAST
LONGEVITY GENE, SIR2, IS EXPRESSED
IN HUMAN SKIN. HISTOLOGICAL STUDIES
Armene Perrin, Eric Bauza, Catherine Gondran, lsabelle lmbert, Claude Dal Forra , Nouha Domloge
Vincience, ISP Global Skin Research Center, Sophia Antipolis, France.
Received: July, 2007
Key words: SIRTI; P53; Skin aging; Ex-vivo human skin; Clinica/ study;
Summary
SIRTJ is the human homologue of Sir2, a key regulator of celi defense and survival in response to
stress. Many studies have investigated the presence of SIRT J in d ifferent hu man tissues, however, no
previous studies have involved human skin. Consequently, we became interested in investigating the
expression of SIRTI in hu man skin under different conditions includ ing UV stress and celi senescence.
Ou r studies involved in vitro-aged human keratinocytes and fibroblasts as well as comparative immunohistological analyses between frozen and fresh ex vivo skin samples, and between skin samples of
different ages. Severa! unmask ing protocols were used in these investigations.
Immunofluorescence staining studies showed that SIRT l is expressed in human skin. In fresh ex vivo
skin samples, SIRTI exhibited a predominantly nuclear staining pattern throughout the epidermis.
Comparative studies of skin samples from donors of different ages did not reveal any significant agerelated difference in SIRTI level, under unstressed physiological conditions. Interestingly, when skin
samples were irradiated with moderate UVB doses, a dose-dependent increase in SIRTI nuclear
expression was seen, which is an interesting new finding. However, high UVB doses yielded strong
p53 expression, which correlated with tissue damage. Simultaneously, celi senescence stud ies have
demonstrated that SIRTI induction in aged human skin cells correlates with a decrease in the expression of a senescence marker and with an extension of the lifespan of these cells.
Ali together, these studies demonstrate that SIRT l is expressed in human skin, and that its expression
correlates with its protecti ve role.
Riassunto
SIRT 1 è l'omologo di SIR 2, regolatore chiave delle difese e della sopravvivenza delle cellule sottoposte a stress.
133
SIRTI, the human homologue of the yeast /ongevity gene, Sir2, is expressed in human skin.
ted Streptavidin (DAKO, Glostrup, Denmark)
diluted at 1: 1000 in PBS for 20 minutes. The
sections were incubated with 3.3'-diaminobenzidine substrate (DAKO, Glostrup, Denmark) for
an egual length of time, washed with PBS to stop
the reaction , and then dehydrated with alcohols
and xylene. Finally, the slides were mounted
with a hydrophobic mounting medium (Eukitt,
O. Kindler GmbH & Co, Freiburg, Germany).
For immunofluorescence staining, after incubation with the primary antibody the sections were
washed with PBS and then incubated with a
secondary antibody, donkey anti-rabbit Alexa
488 (Molecular Probes, Eugene, OR , USA) diluted at 1: 1000 in PBS. The slides were then
mounted with an aqueous mounting medium
(Fl uoromount-G, Electron Microscopy Sciences,
Hatfield, PA , US A) . Immunostaining was visualized using an Eclipse E600 microscope (Nikon,
Champigny sur Marne, France).
U nmasking protocols included pepsin digestion
with 0.25% pepsin (SIGMA, Saint Louis , MO ,
USA) for 30 minutes at 37°C, tryps in digestion
with 0.05% trypsin (Zymed, San Francisco, CA,
USA) for 15 minutes at 37°C, microwave ex posure at 750W in citrate buffer (0.0lM , pH6) for
4 x IO seconds after boiling, water bath for 50
minutes at 95°C in citrate buffer (0.0lM, pH6),
and exposure to 0.5% Triton-X 100 detergent for
30 minutes at room temperature.
In vitro-aged cells and
senescence-associated
beta-galactosidase staining
One week daily treatment with a patented SIRTinducing active ingredient was performed on in
vitro-aged human keratinocytes (P5) and on in
vitro-aged human fibroblasts (P 16) seeded in
lab-tek. For one month treatment on in vitroaged fibroblasts (P30), cells were grown in T75
flask and transferred in lab-tek the last week. At
the end of treatment, cells were washed in PBS ,
fixed for 3-5min at room temperature in 2% formaldehyde I 0.2% glutaraldehyde, washed, and
136
incubated overnight at 37°C with fresh senescence-associated ~-Gal (SA-~-Gal) stain sol ution at lmg/ml. Finally, slides were mounted in
aquatex and visual ized using an Eclipse E600
microscope (Nikon, Champigny sur Marne,
France). Senescent human cells expressing SA~-Gal were detected by X-Gal staining, wh ich
forms a locai blue precipitate .
Skin samples cultured for multiple
days
6mm-biopsies of normai human skin , obtained
post-plastic surgery, were cultured for 5 or 9
days on inserts containing culture media prepared with l g/L glucose DMEM: Ham's ( 1:1 ),
SVF 10%, and 2mM glutamine (Cambrex,
Verviers, Belgium) , and lOOµg/mL primocin
(lnvivogen, San Diego, CA, USA). A patented
SIRT-induci ng active ingredient was applied
daily to the skin biopsies and finally, the samples
were submitted to standard Hematoxylin &
Eosi n (H&E) staining for morphological studies.
MTT Assay
Assays were performed on young (P2) and on in
vitro-aged (P6) human primary keratinocytes.
Cells were seeded in 96-well plates and treated
once a day for 72h with the patented SIRT-inducing active ingredient. At the end of the incubation time, cellular viability was evaluated by
MTT colorimetric assay.
RESULTS
These studies revealed similar results between
the different unmasking protocols and showed
that the treatment of choice was microwave
exposure. The studies also demonstrated that in
fresh ex vivo skin samples , SIRTI is expressed in
the epidermis and dermis which supports the
importance of the role of Sirtuins in celi aging
and the crucial necessity of the presence of
A. Perrin, E. Bauza, C. Gondran, I. lmbert, C. Dal Farro, N. Domtoge
Sirtuins in cells.
In addition, SIRTI exhibited a predominant
nuclear staining throughout the epidermis in
these studies. Some cytoplasmic staining was
also observed (fig 1).
Surprisingly, a predominant cytoplasmic staining was observed in studies of different frozen
ski n samples. However, in a very small portion
of these samples , nuclear and perinuclear staining was observed (fig 2).
Comparative studies of skin samples from
various donors revealed a moderate difference in
degree and pattern of SIRTI expression. These
differences included a predominant nuclear staini ng with and without some perinuclear staining ,
and some cytoplasmic staining in addition to
nuclear staining (fig 3).
Interestingly, parallel comparative studies of
skin samples from donors of different ages (30 to
55) did not reveal a significant age-related difference in SIRTI expression under stress-free conditions (fig 4) .
When skin samples were irrad iated with UVB
(50-200 mJ/cm2), fresh skin samples exhibited a
clear dose-dependent increase in SIRT l nuclear
expression , up to 100 mJ/cm2, which correlated
with low tissue damage and low p53 expression,
whereas high UVB doses yielded strong p53
expression. Very interestingly, these results were
more apparent in young skin (fig 5, 6).
Fig. I SIRTl expression in fresh human ex vivo skin.
Fig. 2 SIRTl expression in frozen human ex vivo skin.
137
SIRTI, the humon homo/ogue of the yeost Jongevity gene, Sir2. is expressed in human skin.
Fig5C
Fig5D
No UVB (A), 50 mJ/cm 2 (B),
100 mJ/cm 2 (C), 200 mJ/cm 2 (D)
Fig. 3 SIRTl expression in fresh human ex vivo skin.
Fig. 5 SIRTl expression in skin from a 30-year-old
donor irradiateci with different doses of UVB.
Fig4A
Fig4B
Fig4C
Fig4D
Fig6A
Fig6B
Fig6C
Fig6D
30-year-old (A), 35-year-old (B),
40-year-old (C), 50-year-old (D)
No UVB (A), 50 mJ/cm2 (B),
100 mJ/cm 2 (C), 200 mJ/cm 2 (D)
Fig, 4 SIRTl expression in skin from donors of
Fig, 6 SIRTl expression in skin from a 35-year-old
different ages.
138
donor irradiated with different doses of UVB.
A. Perrin, E. Bauza. C. Gondran. I. lmbert. C. Dal Farro. N. Oomloge
Fig 7A: Contro!
Fig 7B: SIRTI-induced cells
Fig. 7 Beta-galactosidase staining in in vitro-aged human keratinocytes (P5) after treatment with the
SIRTl-inducing active ingredient for one week.
Fig 8A: Contro!
Fig 8B: SIRTl-induced cells
F ig. 8 Beta-galactosidase staining in in vitro-aged human fìbroblasts (P16) after treatment with the
SIRTl -inducing active ingredient for one week.
Fig 9A: Contro!
Fig 9B: SIRTl-induced cells
Fig. 9 Beta-galactosidase staining in in vitro-aged human fìbroblasts after treatment with the SIRTl -indu-
cing active ingredient for one month (P30).
139
SIRTI, the human homologue of the yeast longevity gene, Sir2, is expressed in human skin.
In parallel, studies on aged human sk.in cells
have evidenced that the expression of the senescent biomarker beta-galactosidase, was considerably diminished in the SIRTl-induced cells .
The aged SIRT-1 induced cells exhibited a
decrease in number of stained cells and in staining intensity, compared to the contro! (fig 7, 8,
integrity were clearly more preserved in SIRTl induced skin samples than in contro! skin (fig
10, 11 ) .
Moreover MTT studies revealed an increase in
celi viability in the SIRTl-induced cells, compared to the contro! cells where SIRTI was not
induced (fig 12, 13).
9),
Supplementary histological studies, on human
sk.in samples after multiple days in culture, have
confirmed that skin morphology, structure, and
Fig IOA: Contro! skin
Fig lOB: SIRTl-induced skin
Fig.10 H&E of skin samples after 5 days in c ulture.
Fig l IA: Contro) skin
Fig, 11 H&E of skin samples after 9 days in culture.
140
Fig l IB: SIRTl-induced skin
A Perrin. E. Bauza. C. Gondran. I. /mbert. C. Dal Forra. N. Domloge
MTT celi viability test on young human
keratinocytes
140
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80
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141
SIRTI, the human homologue of the yeast longevity gene, Sir2, is expressed in human skin.
DISCUSSION
O ur results demonstrated that fresh ski n samples
are the best substrate for SIRT studies , and showed the predominant nuclear ex pression of
SIRTI in fresh skin epidermal keratinocytes and
derma! fibroblasts . Surprisingly, frozen ski n, by
contrast, exhibited mostly cytoplasmic staining
and very rarely exhibited nuclear staining of
SIRT I , and this result was consistent despite the
rapid freezing procedure of skin specime ns.
Moreover, studies on SIRTI expression in fresh
skin samples from different donors revealed a
great similarity in the nuclear expression pattern.
However, some perinuclear and cy toplasmic
staining was observed in a small number of samples. This small variation in express ion pattern
could be due to the state of the donor when the
biopsy was taken, and to the accompanying role
played by SIRTI in diffe rent situations.
It is known that different stress signals that
include important DNA damage, lead to p53 protein increase in the nuclei where it plays its role
in transcription activation. P53 the n launches the
apoptosis process by inducing Fas/CD95 expression and the Fas L ligand binding,
Very interestingly, SIRTI studies on UY-exposed skin showed that SIRTJ expression increased in re lationship to skin irradiation by UVB , in
a dose-dependent manner, up to I00 mJ/cm2.
This new finding is very important and points to
a n add itional protective role that SIRTI plays in
skin physio logy by deacetylating p53 and other
key molecules.
This fi nding was confirmed by p53 expression
studies of skin samples wh ich demonstrated very
low p53 expression and an increased expression
of SIRTI under moderate UVB doses, with
minor accompanying celi damage .
Under stronger damaging UVB doses, an increase in p53 expression was observed in parallel
with a decrease in SIRTI leve!, showing a domi nance of the p53 pathway over the action of
142
SIRTI on celi survival, ind icating a n increased
likelihood of celi death . To our kno wledge , the
role of SIRTI in relation with p53 expression
under moderate doses of UVB had not yet been
described .
In addit ion to these new findings, celi senescence studies using a specific biomarker that is
absent from qu iescent and differenti ated cells
have clearly confirmed the fundamental role of
SIRTI against skin aging.
Indeed, a decrease in the numbe r of cells entering in senescence was observed in cells induced-SIRT I expression. These data were also
confirmed by an improvement of aged cells viability.
Moreover, histological stud ies on huma n ski n
samples have revealed that the skin was clearly
more preserved in S IRT- 1 ind uced skin samples
than in contro! skin which ex hibited the usual
stress and signs of damage that accompany multiple days in cultu re.
Fu11hermore, under no stress conditi ons, stud ies
on skin samples from donors of d ifferent ages
did not reveal a clear relationship between age
and basic SIRTI expression in cells. This finding
furthe r substantiates the notion that the presence
of SIRT is necessa ry for celi survi va l.
Nevertheless, in irradiated aged skin , SIRTI
ex pression and its re lationship with UVB dosage
and p53 ex pression was less obvious than in
younger skin samp les . This interesting result
correlates with the defective functioning of some
key molecules that may accompany, or induce,
aging.
In conclusion, these stud ies demonstrate the
clear and strong expression of SIRTI in human
skin , and propose an additional protective role
for SIRT I against e nvironmental stress, such as
UV. Moreover, the results also suggest that
SIRTI expression optimization in the skin could
be of great use in the fight agai nst agi ng.
A. Perrin. E. Bauza, C. Gondran, I. lmbert. C. Dal Forra. N. Domloge
References
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Caenorhabditis elegans. Nature 410(6825): 227-30.
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7) Finkel T. (2003). Ageing: A toast to Jong !ife. Nature 425(6954): 132-3.
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9) Langley E, Pearson M, Faretta M, Bauer UM, Frye RA, Minucci S, Pelicci PG, Kouzarides
T. (2002). Human SIR2 deacetylates p53 and antagoni zes PML/p53-induced cellular senescence. EMBO J. 21(10): 2383-96 .
10) Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe
M, de Cabo R, Sinclair D. (2004). Calorie Restriction Promotes Mammal ian Celi Survival by
lnducing the SIRT l Deacetylase. Science 305(5682): 390-2.
11) Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, Guarente L, Weinberg
RA. (2001). hSIR2(SIRTJ) functions as an NAD-dependent p53 deacetylase. Celi. 107(2): 14959.
12) Onyango P, Celie I, McCaffery JM, Boeke JD, Feinberg AP. (2002). SIRT3 , a human SIR2
homologue, is an NAD-dependent deacetylase localized to mitochondria. Proc Nati Acad Sci U
SA . 99(21): 13653-8.
13) Kaeberlein M, Andalis AA, Fink GR, Guarente L. (2002). High osmolarity extends I ife span
in Saccharomyces cerevisiae by a mechanism related to calorie restriction. Mal Celi Biol. 22(22):
8056-66.
14) Masoro EJ. (2004). Role of sirtuin proteins in !ife extension by calorie restriction. Mech Ageing
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activators mimic calorie restriction and delay ageing in metazoans. Nature 430(7000): 686-9.
16) Brunet A, Sweeney LB, Sturgill F, Chua KF, Greer PL, Lin Y, Tran H, Ross SE,
Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA,
Alt FW, Greenberg ME. (2004). Stress-dependent regulation of FOXO transcription factors by
143
SIRTI, the human homologue of the yeast tongevity gene. Sir2. is expressed in human skin.
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17) Bordone L, Guarente L. (2005). Calorie restriction, SIRTI and metabolism: understanding longevity. Nat Rev Mal Celi Bial. 6(4): 298-305.
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Author Address:
N. Domloge, MD
Skin Biology and Evaluatio n Department
Vincience
ISP Global Skin Research Center
BP 2 12 - Sophia Antipolis 06904
France
Fax: +33-4 89 73 16 l O
E-mail: [email protected]
144
J. Appl. Cosmetol. 25, 145-159 (October/December 2007)
FLAVONOIDS: A REVIEW FOR COSMETIC
APPLICATION. PART TWO
Mrs.ir. Elzbieta E.Brand-Garnys ',Dr. Horst Denzer ', Dr. Hamke Meijer', Dr.ir. Hans M.Brand '
' ELZBIETA COSMETICS B.V.. Nieuwerkerk a/d IJssel - The Netherlands
' KAO CHEMICALS GmbH, Emmerich - Germany
Received: March, 2007.
Key words: Bio-active substances; Biologica/ extracts; Enzyme manipulation; Enzyme
cofactor;
Summary
Flavonoids are now recognised as essential dietary components, although their functions are just on
the brilli< of understanding. Dietary requirements have been established. Their significance is probably egual to vitamins. Approximately 5000 flavonoids have been identified, and the list is quickJy
expanding. The functionality of flavonoids is frequently " multi-purpose", contrary to vitamins, enzymes and (to a !esser extent) hormones .
Riassunto
I flavonoidi sono riconosciuti come componenti essenziali delle diete, anche se non sono state ancora comprese appieno le loro funzioni. Comunque ne è stato riconosci uto il loro ruolo dietetico che
dovrebbe essere simile a quello delle vitamine.
Circa 5000 sono i flavonoidi già identificati ed il loro numero si incrementa di continuo. Al contrario delle vitamine, degli enzimi e degli ormoni, l'attività di questi composti naturali è più complessa
e serve a molteplici scopi.
145
Flovonoids: o Review for Cosmetic Applicotion
BIOSYNTHESIS OF
FLAVONOIDS
Robinson (8) suggested that the C 15-skeleton of
flavonoids is composed of two parts: a phenolic
compound with six carbon atoms and an alkyl
substituted phenolic compound with nine carbon
atoms. The tota! biosynthesis is not yet known,
but it has been shown, that the phenolic compound with six carbon atoms is constructed from
acetic acid using acetyl-coenzyme A. This was
concluded from feedi ng red cabbage plants with
14
C-labelled acetic ac id. Severa) authors also
suggest that malonyl-coenzyme A is involved in
this process. Virtually ali reaction sequences in
the biosynthesis of flavonoids are enzyme controlled. Typical phenolics are catechol, quinol
and resorcinol.
The alkyl substituted phenolic compound follows the shikimic acid (3,4,5-trihydroxycyclohexene-1-carboxylic acid) pathway. This results in
the formation of (substituted) cinnamic acid.
This has been concluded from experiments using
14
C-labelled shikimic acid, phenylalanine and 4hydroxycinnamic acid, which ali showed to be
precursors for quercetin. It has become evident,
that especially phenylalanine plays a determining role in the biosynthesis of flavonoids.
THE FUNCTIONALITY OF
FLAVONOIDS
Relative to the functionality of flavonoids most
attention has probably been given to their ability
to act as powerful anti-oxidants. The US
Department of Agriculture have done and delegated a wide variety of studies relative to the
anti-oxidant properties of flavonoids and has
defined the so-called Oxygen Radical
Absorbance Capacity (ORAC). Among fruits
prunes are the absolute Jeaders when it comes to
ORAC value, while red grapes, blueberries and
146
raspberries are excellent followers. In the range
of vegetables spinach, Brussels sprouts, alfalfa
and broccoli score high. A recent study showed
that a high ORAC diet raised the antioxidant
capacity of the blood in the range of 10-25%.
Table XI and XII give some ORAC data of particular flavonoids.
Table XI
ORAC values expressed as
concentration. (in 11Mole)
whereby 50% inhibition
of lipid peroxidation occurs.
Baicalein
Quercetin
Myricetin
Galangin
Kaempferol
Baicalin
Fisetin
6,3
8,5
10,5
13,8
19,0
20, 1
Mo rin
Hyperoside
20,8
23,0
59,5
Rutin
93,5
Also the antioxidant qualities of green tea flavonoids can clearly be demonstrated using the
ORAC values (9, 10).
The ORAC values of antioxidants are not only
significant for food additives but also for persona! care and cosmetics. Skin ageing is usually
related to lipid peroxidation and thus oxidation
of the bio-membranes present in the sub-cutaneous tissue. Also oxidative stress, oxidation of
squalene to squalene hydroperoxide instead of
squalene-2,3-epoxide (which is the precursor for
steroid hormones) is a significant ageing factor.
The efficacy of flavonoids as anti-oxidants is
related to their ability to quench oxygen-based
free radicals, such as singulet oxygen, Ho2 · and
E. E.Brand-Garnys, H. Denzer. H. Meijer. H. M.Brand
HO' , but also NOx'. Free radicals are often
brought into connection with the occurrence of
skin defects and premature skin age ing, particularly in conjunction with over-ex posure to UV-A
and UV-B rad iation (photo-ageing; dermatoheliosis). In cosme tic practice it is common practice to compensate these effects using vitamin e
a nd/or vitamin E. Topica! application of flavono ids such as que rcetin and ru tin (the glycos ide
of quercetin with rutinose; rutinose is the disaccharide of glucose a nd mannose) has been
shown to be at least 60 times more acti ve than
ascorbic acid (vita min C) a nd 350 times more
tha n tocopherol (vitami n E) . In actual fac t, tocophe rol is only a weak anti-oxidant.
Jt was also fou nd that many fl avonoids are able
to protect human dermal fibroplasts signifi cantly
better than vitam in C/E , irrespective the stabil ity
of especially vitam in C: ORAC values of ascorbic acid and d-a-tocophe rol are in the mMo le
range.
Jn add ition, flavonoids are also a ble to protect
products vulnerable to oxidation, such as ascorbic acid and tocopherol, and it is the refore not
surprising that e.g . the comb inati on { vitamin
C+rutine} is much more effecti ve than the individ uai ingredients . After ali , vita min C is a n
important co-factor for various enzy mes; skin
lightning is a beautifu l exponent thereof.
The protective effec t of flavonoids obtained
from bilberries and grapes has been de monstrated by Monboisse et.al (11) . Calf skin ac id-soluble co llagen was exposed to free oxygen rad icals
produced by xanthine oxidase/hypoxanthine.
Determi nation of the level of 4-hydroxyproline
was monitored and it was shown that the collagen degradation could be completely inhi bited
with these flavonoids .
Many flavonoids exhi bit anti-allergic properties
and some are claimed fo r their anti-viral properties ( 12) . Hesperidin, rutin, querceti n, quercitrin
and aurantiin were examined against vesicular
stromatitis virus (YSY) action on mouse fibroplasts and hesperidin was also tested agai nst
influenza virus . Protection could be achieved for
a period of 24 hours fora one-dose appl ication
of 200 µg/ml flavonoid . The results a re preventive rather than curati ve, but this application
seems to be most suitable indeed for skin care
products for the inhibition of topically active
viruses such as the herpes simplex virus . It goes
without saying that cosmetic products, especialIy facial care, are usuall y prophylactic rather
than reparative.
Also a large number of references have been
made to the anti-inflammatory, anti -thrombotic ,
d iuretic, fung icide and bactericide activity of flavonoids.
Significant is also the sti mulat ing effect to protein synthesis . Many of these properties boil
down to the ability of flavo no ids to interact with
ali kinds of e nzymes.
A number of flavono ids have been demonstrated
to be co-factors for enzy mes. In th is te rmino logy
they could be considered compara ble to vitamins.
Table XII
ORAC va/11es of some green tea flavonoids
(-)-(2R,3R-Epicatecin Gallate
(-)-(2R,3R-Epigallocateci n Gallate
(-)-(2R,3R-Epigallocatecin
(-)-(2R,3R-Epicatecin
10,0
11 ,0
16,0
30,0
147
Ftovonoids:
o Review tor Cosmetic Applicotion
Although in many cases onl y a limited selectivity of flavonoids fo r particul ar enzymes is observed , an increasing number of publications appear in the scientific literature reporting about an
unexpectedly high degree of selectivity for partic ular enzymes.
It has been shown that many flavonoids are able
to strengthen the fragile capillary blood vessels,
and thus are an excellent tool to fight couperosis.
Frequently the d amaged blood vessels, particularly around the nose and on the cheeks will
negati vely influence the fac ial appreciation.
Ginkgo biloba is a we ll- known source for flavonoids, and this extract is a very potent product
to treat couperosis. This effect has also been
observed using rutin when mice were exposed to
excessive X-raying, whi ch results in destruction
of the arteries (Bruckne r). The rate of survi val
inc reased from 31 % to 56%. For that reason
rutin is used for treating radiation sickness in
men, e.g. the victi ms of radiation accidents in
nuclear installations and it is also clinically
applied for patients that suffer from erythraemia
due to y- irradiation.
A greatly less examined source of fla vonoids for
use in persona! care and cosmetics are extracts of
d ifferent nuts such as bitte r almond (Prunus
a mygdalus), plums (Pru nus domestica, containing the flavonoid pruneto)) and black cherry
(Prunus serotina). These extracts are very potent
inhibitors for a number of enzymes. It is also
inte resting to note that the fatty acid composition
of black cherry oil (also named wi ld cherry oil)
a nd prune oil is fully in line with the chemical
properties of the flavonoids as they occur in the
frui t flesh.
T he extract of peach (Prunus persica) and apricot (Prunus armeniaca) contain the fla vonoid
prunasin that inhibits the conversion of dopac hrome to melanin, and for obvious reasons
these extracts have been proposed and patented
fo r skin whitening.
Flowering peach (Prunus davidiana) is already
known for 3000 years to lower glucose levels in
148
the blood of diabetes type II patie nts. It certainly is a functional remedy to treat type II diabetes
patients, but this prope rty also could be applied
for slimming products. The acti ve substances
have been dete rm ined as flavonoids: catechin ,
prunin (naringenin-7-0-glucoside) and hesperidin-5-0-glucoside. Also myriceline and dihydromyriceline have been proposed for that application.
In addition to the anti-oxidant activity the physiological effects of ma ny flavonoids can be
explained as a disti nct influencing of the enzyme
system of the organism. Application can be do ne
orally or topically. Given the fact that many flavonoids are water-soluble, transdermal application is certainly a valid mechanism , and probabl y better controll able than ora! or intravenous
appl ication . However, ma ny fla vonoids are
poorly soluble and will precipitate/crystall ise at
room temperature. In that case excellent results
have been obtained by incorporation of flavonoids such as quercetin an/or rutin in the liqu id
crystalline matri x of suitable emulsifiers. The
flavonoids are mono-molecularly soluble in the
liquid crystall ine matrix and the bio-availability
is therefore s ignificantly higher compared to a
system that does not util ise a liquid crystalline
matrix. lt has also been demonstrated that the
acti vity of poorly soluble flavonoids can be
improved when applied in unsaturated phosphatidyl choline organogels.
Rutin (and to a !esser extent esculetin) are wellknown inhibitors for the enzy mes aldose red uctase, lipoxygenase and phosphodiesterase. It dramatically stre ngthens the capillaries, has bactericide and antiviral properties, and a variety of
properties that are pharmaceutical by nature.
Rutin is also highly appreciated for its ability to
avoid erythraemia. This is beneficially applied in
sun care products, hav ing said that rutin is not
class ified as a UV fi lter.
The 3-rhamnoside of the flavonoid quercetin is
named quercitrin . Quercetin a nd quercitri n occur
in apples, ali kinds of berries, onions (in The
E. E.Brand-Garnys, H. Denzer, H. Meijer, H. M.Brand
Netherlands 54% of the ora! flavo noid intake
comes from onions, and 28% from apples), but
also in nuts, flowers and the bark of many trees
to which it gives a typical yellow colour.
Quercetin also occurs in significant amounts in
botanica! extracts such as Gi nkgo biloba (ginkgo), Hypericum perforatum (St.John 's wort),
Sambucus canadensis and Sambucus nigra
(elder). Quercetin and quercitrin are potent antioxidants and have a strong interaction with
enzymes. Quercetin inhibits xanthine oxidase
and in vitro experiments have shown that it also
inhibits lipid peroxidation. This is most significant indeed as peroxidation of the unsaturated
fatty acids in the subcutaneous membranes
res ults in premature ageing.
Anti-inflammatory properties of quercetin and
quercitrin appears to be due to its anti-oxidant
and inhibitory effects on inflammation inducing
enzy mes such as cyclo-oxygenase and lipoxygenase, and the subsequent inhibited formation of
leukotrienes and prostaglandins. There is also
evidence that quercetin and quercitrin inhibit
elastase, collagenase, hyaluronidase and tyrosinase. Ali these enzymes are most significant to
the cosmetic chemist as they enable to contro!
and manipulate the quality of the skin. No data
on ad verse effects of excessive dosage of flavonoids have been reported. The effective concentration of flavonoids such as quercetin, quercitrin and rutin in cosmetic preparations is low
(0,05-0 ,15%), although also at this low concentration the solubility of these flavonoids may be
a limiting factor in formulation development.
Noteworthy is the normalising effect of flavonoids on the enzyme system. Many processes
that result in skin disorders boil down to a disturbed enzyme balance on the skin and in the subcutaneous tissue . Flavonoids are a fabulous and
safe tool to alleviate these disorders. Although
many botanica! extracts are also a significant
source for flavonoids, their concentration is
usually significantly lower and to reach a similar
leve! of bio-activity a high concentration of
botanica! extract is req uired, to such an extent
that also side effects of undesired products may
become apparent.
BOTANICAL EXTRACTS RICH
IN FLAVONOIDS
Botankal extracts are often rich in flavonoids,
and the diversity can be massive. In many publications first priority is given to the antioxidant
properties of these flavonoids, but it has become
clear that flavonoids have a far more significant
role in topically applied products. Many flavonoids act as co-factors forali k.inds of enzymes.
As an example 3-galloyl-3' ,4 ' ,5,5 ' ,7-pentahydroxyflavanone (EGCG), a flavonoid that occurs
in camellia sinensis (green tea), has been demonstrated to inhibit the enzyme squalene monooxygenase . This reaction is important for the conversion of squalene to lanosterol/cholestero.I
(1 3) .
Enzyme manipulation via flavonoids is probably
a generai working mechanism in the human
body by adjustment of the dietary habits, but
also on the surface of the body via persona! care
and cosmetic products . The tota) amount of flavono ids acqu ired via the daily food intake has
been shown to be insufficie nt because of improper dietary habits. Consequently the amount of
fla vonoids topically present is in generai insufficient to allow the topica) enzyme system to perform smoothl y. A similar discussion continuously takes place on vitamins (also important, indispensable, cofactors for enzymes).
Chamomile (Chamomilla recufita)
Three well-known species of chamomile are in
use: German or wild chamomile (Chamomilla
recutita), Roman chamomile (Anthemis nobilis)
and golden chamomile (Anthemis tinctoria) .
Roman chamomile is commerciall y cultivated .
Chamomile is an extremely rich source of flavo-
149
Flavonoids: a Review far Cosmetic Application
noids: apigenin , Juteolin , quercetin , apiin , isorhamnetin, patuletin , and a wide variety of glycosides such as apigetrin-7-acetylglucoside, luteolin-7-glucoside, luteolin-4'-glucoside, luteolin7-ruti -noside, 6-hydroxy-luteolin-7 -glucoside,
quercimetrin , patulitrin , rutin, hyperoside, isorhamne tin-7-glucoside and c hrysoeriol-7-glucoside. Also a number of coumarins are present,
specifically to be menti oned coumarin , umbellifero ne, methylumbelliferone and herniarin.
Luteolin , as it occurs in chamom ile, is a high ly
useful substance; re ported activities: aldosereductase inhibitor, antiang iogenic, anticarcinogenic, antioestrogenic, a ntimutagenic , antitumour (powerful), no-synthase inhibitor, metalloproteinase inhibitor, succinoxidase inhibitor,
xanthine oxidase inhibitor, topoisomerase inhibitor.
C hamom ile extract has anti-inflammatory, antiitching, anti septic, bactericidal and disinfectant
properties. The beneficiai properties of c hamomile extract are well docume nted, and many properties of the chamomile extract that product
development chemists use boil down to e nzyme
manipulation using flavonoids present in the extract.
Amaranth
(Amaranthus caudafus)
In foods, amaranth is used similarly to wheat as
a cerea! grai n. It was one of the staple foodstuffs
of the lncas, and it is known as kiwicha in the
Andes today. It was also used by the ancient
Aztecs, who called it huautli . Amaranth species
are culti vated and consumed as a leaf vegetable
in many parts of the world. In Indonesia ,
Malays ia and China it goes by the name
"bayam".
Orally, amaranth is used for the treatment of
ulcers , diarrhea, and infla mmation of the mouth
and throat. It is also used orally to treat hypercholesterolemia and for the treatment of impure
150
ski n. The following substances are listed in the
literature as actives of the plant: amaranthin ,
rutin (quercetin-3-rutinose) and two other yet
unidentified complex glycosides deri ved from
quercetin . Amaranthin is not a flavonoid but an
indole-based betaine with two sugar moieties
linked to it (one is a hexuronic acid).
Khella (Visnaga vera)
Khel la grows in the Mediterranean countri es, but
has also been brought to the Middle East and
South America. Khella is commercially culti vated in the United States. It is used in locai medicine for the treatment of bronchitis, coug hs, hi gh
blood pressure, proble ms with the li ver and gallbladder, but most of a li fo r coronary di seases . It
fortifies the arteries and is known to act on irregular heartbeat. In the treatment of kidney stones
it ass ists to relaxing the ducts to the bladder,
al lowing the stones to pass.
The principal active ingredient in khe lla extract
is khelline (v isamine), present in 0 ,3-0,4% .
Khelline has outspoken vasodilatory and vasoprotective properti es, a nd therefore khella
extract is most suitab le for the treatment of coupe rosis.
Next to khelline a wide variety of other fla vonoids are present, more specifically myricetin-3glucoside, myricetin-3-rhamnoglucoside, rutin ,
isoque rcetin , kaempferol-3-rutinoside and astragalin .
Also flavonoids structural ly related to khelline
(which has a psoralen structure) are present, to
be mentioned visnad in , samidin , dihydrosamidin , visnagin , visammidin , visnagenin and
visnagidin.
Khella e xtract is not subject to restrictions for
use in persona! care and cosmetic products,
which is surpri sing given its potential.
Khella extract shall not be used in daytime
cosme tics , but preferably in night care cosmetics
or in products such as masks.
E. E.Brand-Garnys, H. Denzer, H. Meijer, H. M.Brand
hamnoside, kaempferol coumaroyl glucorhamnoside, luteolin glucoside and leuco-anthocyanins .
OH
HO
O=t1 o-eI
H3C
-
'cH-CH2CH3
OH
...'OH
tH3
A CATECHIN
VISNADIN
Ginkgo (Ginkgo bilobo)
Ginkgo biloba, also named maidenhair tree, is
the last me mber of the Ginkgoaceae which had
their first appearance on Mother Earth some
200-250 mi llion years ago. Darw in named it a
li ving fossi!. Ginkgo contains some unusual chemical substances that are found nowhere else in
nature : bilo balide (a sesquiterpene), gi nkgo lides
(diterpenes with 20 carbon atoms) and aromatic
prod ucts suc h as ginkgo), bilobdol and ginkgolic
acid. Little is known about the phys iological
effects of these substances, although gi nkgo
extracts are used in traditional medicine for 4000
years for the treatment of a variety of di sorders
and complaints. Ginkgo biloba extract is also a
valuable source for shikimic acid , a building
block for the synthesis of flavono ids, in a comparable fashion as phe nylalanine .
Ginkgo extract is also a very rich source for flavonoids. The extract contains quercetin, isoquercetin , isorhamnetin, kaempferol, myricetin, bilobetin (only one source known , and this is also
val id for ginkgetin and isoginkgetin), sciadopytisin.
Also a variety of glycosides is present such as
quercetin-3-rhamnoglucoside, kaempferol-3rhamnoglucoside, quercetin coumaroyl gl ucor-
A number of catechins is present such as catechin , epicatech in, gallocatechin and epigallocatechin.
Catechins aJso belong to the group offlavonoids,
but lack (compared to flavanones) the carbonyl
group on the 4-position (catechins can be considered as " hydroge nated anthocyanidi ns") .
Because of the saturation of the ~2 -3 double
bond a chiral cente r is prese nt on the 3-position.
Both enantiomers do occur naturally.
Traditionally the gi nkgo extract is used to combat disorders of the bronchi al tubes. For persona!
care and cosmetic products enzyme inhibition is
the keyword.
The extract of G inkgo biloba is probably the
strongest botanica! enzyme inhibitor known; a
wide variety of publications on this topic have
appeared in the scientific literature. The extract
inhibits various elastases, the seven hyaluronidases known and a wide variety of phosphatases.
These enzymes exhibit an increasing activity
with increasing age , and result in visi ble signs of
ageing. Consistent use of the ginkgo extract will
notably reduce these effects, and can therefore
be considered as a superior anti-ageing product.
Other cosmetically significant properties of the
ginkgo extract are vasodilatation and the stimulating effects. There is sufficient reason to believe that these properties boil down to enzyme
151
Flovonoids: o Review tor Cosmetic Appficotion
inhibition by flavonoids. Also the anti-oxidant
properties (the ability to quench free radicals) of
the ginkgo extract are important, and an important tool to avoid peroxidation of membrane
lipids as well as oxidative stress.
Calendula (Calendula Officinalis)
Calendula extract, or calendula oil , is probably
the most spirited advocate of homeopathy. This
is largely attributed to a wide range of terpenoids
present, but also to flavonoids that occur both in
calendula extract and calendula oil. These have
anti-inflammatory properties, are appreciated
irritation quenchers, and have antiseptic, astringent, fung icide, soothing, wound healing and
tonifying properties. Quercetin is the most
important flavonoid present, next to a wide range
of glycosides of quercetin and isorhamnetin.
Kalvatchev (14) showed that organic extracts of
dried calendula flowers inhibit HIV-l reverse
transcriptase, while aqueous extracts did not
show this property. For this reason the fl avonoids present in this extract are examined on the
potential application for the treatment of HIV
infections, although their mode of action is not
understood.
Quercetin is without doubt the most widespread
fla vonoid that is known . lt indeed is a powerful
anti-oxidant, but it is also a powerful enzyme
inhibitor, in particular for phosphodiesterases
and lipases .
Licorice (Glycyrrhiza glabra)
Licorice extract is a powerful extract, and the
basis for that is the presence of qui te a number of
flavonoids: glabradine , liquiritine, isoliquiritine,
liquiritigenin , isoliquiriti-genine, isoliquiritoside, diglucoliquiritoside, and some coumarins
(umbelliferone and hemiarin). Licorice extract is
also used in food industry to make children's
sweets
152
One of the major functionalities from licorice
extract is the inhibition of two enzymes: tyrosinase and superoxide dismutase. This inhibition
results in a scenario whereby skin lighteni ng can
be ach ieved while reducing simultaneous ly
reducing oxidative stress. This goes hand-inhand with the stimulation of the enzyme squalene monooxygenase to promote the topica! production of cholesterol . Licorice has also bacteriostatic properties that originate from the flavonoid fonnonometin (7-hydroxy-4'-methoxyisoflavone).
Me
Me
OH
GLABRA DINE
Glabradine has been identified as the most active flavonoid . It is, in chemical terminology, a
catechin. The heterocyclic 6-membered ring on
the 7 ,8-position is composed of an isoprene unit
that originates from reaction with dimethylallyl
pyrophosphate (DMAPP). Two additional flavonoids are present that are structurally related to
glabradin (glabrol, formonometin) that are also
physiologically active.
Horse Chestnut
(Aescu/us Hippocastanum)
Horse chestnut is a powerful source for flavonoids . The flavonoid composition is dependant
on the part of the tree that is considered. The
bark contains 3% aescu lin (camarin g lycoside),
aesculetin, aescin, fraxin, scopolin , fraxetin , sco-
E. E.Brand-Garnys, H. Oenzer, H. Meijer, H. M.Brand
poletin, quercitrin, quercetin and leukoanthocyanes. The flowers contain kaempferol-3-glucoside, kaempferol-3-arabinoside , kaempfero l-3rhamnoglycoside, rutin , and isoquercetin. The
seed contains only a minor amount of flavonoids, but the leaves are rich in fraxin and scopolin.
A major property of horse chestnut extract is to
activate those enzymes that are responsible for
stimulation of the hair follicle. Consequently the
extract is frequently used for hair growth preparations. Another significant property of the flavonoids present in horse chestnut is the abi lity to
eli minate bui ld-up of body liquids. The application of a gel containing 5-10% horse chestnut
extract to the legs after an interconti-nental flight
wi ll resolve the edema in 10-15 mi nutes.
THE MOST SIGNIFICANT
FLAVONOIDS
It has been demonstrated that flavonoids are
indispensable products that shall be prut of the
daily d iet, but they ate high ly fu nctional ingredients for persona! care and cosmetic products.
A healthy skin will cover a healthy organism.
For this reason it is useful to discuss the major
flavonoids separately.
Quercetin: 3,3',4',5,7-penfahydroxyflavone
Quercetin (synonyms: meletin, sophoretin , querceto!, xanthaurine, CI 75670, Natural Yellow 10)
is a high melting, yellow solid (3 16-3 17° C). lt
is poorly soluble in water (both cold and warm),
but soluble in warm ethanol and acetone.
Quercetin is also soluble in acetic acid , organic
amines and in alkali . Solutions of quercetin in
alkali are intense yellow. However, because of
the limited solubility in commonly used solvents
applied in cosmetic products complete dissolution may occasionally cause form ulation pro-
blems in terms of bio-availability. This problem
can be bypassed to molecularly dissolving quercetin in a Iiquid crystalline matrix composed of
particular amphiphilic products (emulsifiers).
Quercetin is a powerful anti-oxidant suitab le for
appl ication in food products. The anti-oxidant
properties of flavonoids are easily understood
because of the presence of a large number of
phenolic hydroxy groups, enabling free radicals
leapfrogging over the aromatic system. As an
example, the anti-oxidant properties of quercetin
enable a much better uti lization of ascorbic acid
(vitamin C), having said that ascorbic acid is an
antioxidant by itself.
Quercetin is 20 times more potent than ascorbic
acid, and 50 times more potent than tocopherol
(vitamin E) . It has also been demonstrated that
querceti n is able to avoid oxidation of membrane lipids (usually with a high degree of unsaturation) and to reduce oxidative stress.
In a number of publications synergistic mixtures
have been suggested of quercetin with either
ascorbic acid or ~-glucans, or a combination of
these three ingredients, taking advantage of the
re-enforcement of the auto-immune system by
~-gl ucans . Contrary to statements in earlier
publications it is probably not possible to use
quercetin to guarantee the oxidative stability of
ascorbic acid in cosmetic emulsions.
In a way flavonoids, and quercetin in particular,
can be compared to vitamins. Quercetin has been
identified as a positive or negative cofactor fora
number of enzymes. For both vitamins and flavonoids is valid that the human body is not able
to produce them (with the exception of vitamin
D3 and D4) and is dependant on them via the
intake offood. The average daily intake offlavonoids (in mg) is given in table XlII.
Given the oral intake of relatively large amounts
of flavonoids accumulative and toxicological
effects ha ve been studied in detail. Schneider
(15) showed that Eubacterium ramulus (which
occurs in human faeces) degrades quercetin (and
153
Flovonoids: o Review tor Cosmetic Applicotion
also rutin, kaempferol, luteolin, luteolin-7-glucoside, eriodictyol , naringenin , tax ifolin and
phloretin) to phenolic acids, in the case of quercetin to 2,4,6-trihydroxybenzoic acid.
The FDA has nominated quercetin for toxicity
and carcinogenicity studies in the rat as quercetin is subject to a considerable dietary intake.
The study was done via a two year feeding study
on male and fornaie F344/N rats. The results
indicate that there is no evidence of toxic and/or
carcinogenic activity in fornaie rats, and that
there was onJy minor and insignificant evidence
on male rats, receiving 1.000, 10.000 and 40.000
ppm (max.4%) .
Quercetin is a powerfu l enzyme manipulator.
Thome et.al. (16) demonstrated that q uercetin
selectively inhibits the activity of JE5-lipoxygenase and other enzymes known to be involved in
the metabolism of arachidonic acid in cells.
Quercetin exhibits both allergie mediator release
activity and selective inhibition of the biosynthesis of pro-inflammatory arachidonic acid metabolites, and is a prototype for the development of
new anti -allergic and anti-inflammatory compounds. These properties make quercetin to a
highJy desired product for cosmetic products.
Castelli (17) showed that a combination of ginkgo extract and carboxy-methy l- 1 ,3-~-glucan
applied to the skin for two weeks significantly
reduced dermatitis fora number of allergens fo r
a large group of woman in a double blind study.
Analysis by GC/MS showed that quercetin and,
to a !esser extent, kaempforol were responsible
for the observations .
In addition, Kim ( 18) showed that the flavonoids
present in ginkgo extract stimulates proliferation
of human skin fibroplasts and increase the production of collagen and extracellular fibronectin .
Quercetin is heavily involved in this process,
next to ginkgolide, bilobalide, kaempferol and
sciadopitysin , and that both observations bo il
down to enzyme inhibition.
Quercetin showed to be potent in the cytotoxicity against tumor cell lines. Scambia et. al. (19)
demonstrated that quercetin inhibits the growth
of severa! cancer line cells and that the anti-proliferative activ ity is rnediated by a so-caUed type
II estrogen binding site . Many other flavonoids
also have estrogen properties, but quercetin is
believed to be one of the more potent products,
comparable to genistein .
It was remarkable that quercetin showed itself to
be a strong synergist for cis-platinum relative to
the anti-proliforative effects of the ovarian cancer celi line OVCA-433. The effects observed
were demonstrated to originate from enzyme
inhibition.
Quercetin Glycosides
Next to quercetin, an aglycon, also a wide variety of glycosides are known, many of them being
physiologically active products .The hydroxy
group on the 3-position of quercetin may be
occupied by a rutinose unit (6 - (~-1 -1-rhamnosi­
do)-d-glucose) and is named rutin (quercetin-3rutinose) .
Rutin may be extracted from D imorphandra
mollis and Ruta graveolens (Rue).
Table XIII
Average human daily intake offlavonoids.
154
Quercetin
8,5
Rutin
Fisetin
1,5
0,4
Kaempferol
Myricetin
Luteolin
Eriodictyol
0,3
Myricitrin
5,0
0,6
0,3
0,01
E. E.Brand-Garnys, H. Denzer, H. Meijer, H. M. Brand
Historically rue has been used by thousands of
women in Latin America as a contraceptive to
prevent pregnancy. It is known that rutin
responds positively to the calcium and magnesium metabolism, and has potential benefits for
the treatment of osteoporosis.
Rutin has been reported to have anti-oxidant
properties and is vita! in its ability to improve
capillary fragility (increasing the strength of
capi llary blood vessels) and to regulate their permeability.
Rutin has synergistic acti vity with ascorbic acid
in keeping collagen in healthy condition and to
enable proper absorption and use of ascorbic
acid. Rutin inhibits the degradation of collagen
by the enzyme xanthinoxidase to smaller peptides, and has been shown to reduce the activity of
lipoxygenase (tested on soybean lipoxygenase) .
Quercitrin is characterised as the 3-rhamnoside
of quercetin. Quercitrin may occur in either
anhydrous form (MP=250°C) or monohydrate
(MP=l82°C). It is insoluble in cold water but
soluble in hot water. It is also soluble in glacial
acetic acid, ethanol and in alkaline solution.
Alkali ne solutions of quercitrin are very intense
yellow coloured, and may develop a precipitate
in time due to hydrolysis of the glucoside.
Quercitrin is a powerful anti-oxidant. Quercitrin
is well tolerated in the gastro-intestina! tract.
Dong et. al. (20) showed that quercitrin is degraded to either quercetin and rhamnose, but aJso
further degradation (under anaerobic conditions)
occurred, resulting in the formation of 3 ,4-dihydroxyphenylacetic acid and 4-hydroxybenzoic
acid. Both products were identified as the metabolites. 3,4-Dihydroxyphenylacetic acid and 4hydroxylphenylacetic acid are potent in vitro
anti-platelet aggregation activitors .
Polygonum fagopyrum (B uckwheat) is an
important source for quercitrin. The dried leaves
contain 3-8% flavonoids, the majority being
quercitrin and rutin. Significant amounts of
quercitrin are also found in citrus fruits and in
rose hips.
According to a JOmt Canadian/United States
research program quercitrin has been claimed to
be promising for the treatment of various forms
of cancer. This would include prostate cancer,
lu ng cancer, melanoma and breast cancer
(results presented on the 219'h national meeting
of the American Chemical Society). Tangeretin,
nobiletin and quercitrin, flavo noids present in
tangerine juice, were the most effective inhibitors of human prostate cancer cells. These products also inhibited the growth of melanoma
cells and were effective against breast cancer
cells, with comparable activity as tamoxifen
(anti-breast cancer drug). Animai studies are to
date not completed yet.
Quercitrin is useful in the treatment of high
blood pressure due to their capillary-strengthening and blood vesseldi lating properties. It is
also useful in capillary fragility disorders such as
easy bruising, bleeding of the gums, and also in
circulatory disorders of the retina of the eye. It is
particularly useful in the treatment of vein and
capi ll ary problems such as varicose veins,
venous insufficiency (poor return of blood to the
heart from the ve ins of the legs), and eye problems such as diabetic retinopathy and macular
degeneration.
Hyperoside (hyperin , quercetin-3-galactoside) is
found in Hyperic um perforatum (St.John 's
wort). Hyperoside is a powerful anti-ageing product because of the inhibition of the enzyme elastase. Combined with chickweed the extract of
St.John 's wort is useful for the treatrnent of eczema.
Hawthorn (Crataegus pinnatifida) is a thorny
tree, widely distributed in the north temperate
regions. It is an important source of hyperoside,
next to protocatechuic and chlorogenic acid, epicatechin , querceti n, isoquercetin and rutin. The
psoralen leve! is low. Also loquat (Eriobotrya
Japonica) is a valuable source of hyperoside.
Hawthorn and loquat show efficacy on the suppression on the inhibitory effect on Cu 2+ media-
155
Flavonoids: a Review for Cosmetic Application
ted oxidation of human LDL and has a protective effect on a-tocopherol in human LDL.
Hyperos ide
has bactericidal properties
(MIC=250-500 µg/ml) and has been reported as
an anti-viral. It is used to treat fragility of the
capillaries (couperosis), dermatitis, has antiinflamrnatory properties and is cancer preventive.
Isoquercetin (quercetin-3-glucoside) is found in
significant amounts in Equisetum arvense (horsetail). The hollow, jointed stems of this flowerless plant contain large amounts of water-soluble
(5-8%) with excellent bio-availability.
Horsetail reduces the risk of excessive bleeding
and contributes to the building of healthy blood
cells. Topically applied it has positive impact on
the bloodstream. lt has been shown that horsetail
increases the number of phagocytes, germ-killing enzymes, greatly improving the well-functioning of the entire immune system.
Isoquercetin is frequently outperfo rming ~-glu­
cans on the protection of the auto-immune
system.
Horsetail contains a significant amount of isoquercetin (up to 0,5%), next to two flavone glycosides characteristic for horsetail (galuteolin &
equisetrin). The combination of these flavonoids
is responsible for the bactericidal properties.
Like most flavonoids, isoquercetin is a powerful
anti-oxidant.
lsoquercetin is a well-known aldose-reductase
inhibitor. It has also antibiotic and diuretic properties. Some sources for isoquerceti n are
Filipendula
ulmaria
(meadowsweet),
Foeniculum vulgare (fennel), psidium guajeva
(guava) and Viscum album (rnistletoe).
CONCLUSION
Flavonoids comprise a Jarge group of products
that bave similar structural properties. Ali flavonoids are from vegetable origin; many botanica)
extracts contain significant amounts of flavonoids. In many cases the functionality of botani-
156
cal extracts is dedicated to fla vonoids.
Flavonoids are powerful antioxidants, and in virtually ali cases they outperform artificial antioxidants and poor antioxidants such as tocopherol and ascorbic acid. They enable to contro) oxidative stress and peroxidation of membrane
lipids.
Flavonoids are powerful enzyme modulators; in
many cases it has been shown that they are positive or negative cofactors for various enzymes
such as phosphodiesterases, hyaluronidases, elastases, aldose reductases, lipoxydases and lipoxygenases.
The
application
of
flavonoids
in
pharmacy/medical technology and food supplements has been well developed. The appl ication
of fla vonoids in persona! care and cosmetic products is Jess developed , although the use of botanica) products is common practice. Maj or applications of fla vonoids are in anti-ageing, anti-cellulite, anti-couperosis and skin lightening products, and applications as soothing, astri ngency,
bactericide properties, and many others.
The use of purified fla vonoids has a significant
potential in persona! care and cosmetics as the
application of botanica] extracts will never enable to reach a cosmeceutical leve] of acti vity.
This goes together with the fact that raising the
concentration of botanica! extracts in consumer
products implicitly means also an increased
leve] of less desired products (e.g. al kaloids and
saponines) present in the fmal consumer product.
A number of flavonoids are commercially available, such as quercetin, quercitrin, isoquercetin ,
apigenin , biochanin, geniste'ine, daidzein and
rutin.
The beneficiai properties of the use of pure flavonoids start to be recognised by the persona!
care and cosmetics industry. The first consumer
products have already arrived in the market
piace.
E. E.Brand-Garnys. H. Denzer, H. Meijer, H. M.Brand
References
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9) Ghiselli A, Serafini M, Maiani G, Azzini E, Ferro-Luzzi A. (2000). A Fluorescence-based
Method for Measuring Tota! Plasma Antioxidant Capability, Free Radic.Biol.Med., 18: 29.
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Alters the Interactions between Collagens and Human Polymorphonuclear Leucocytes,
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Hesperidin , Arzneim.-Forsch JDrug Res., 28: 347.
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Flavonoids on the Reduction of Progesterone to 20-Alpha-Hydroxyprogesterone in Rat Liver,
J.Ster.Biochem.Mol.Biology, 93: 73.
14) Kalvatchev Z, Walder R, Garzaro D. (1997). Genotoxic and Anti-Genotoxic Properties of
Calendula officinalis Extracts in Rat Liver Celi Cultures Treated with Diethylnitrosamine,
Biomed.Pharmacotherapy, 51: 176.
15) Schneider H, Blaut M. (2000). Anaerobic Degradation of Flavonoids by Eubacterium ramulus,
Archives of Microbiology, 173: 71.
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Alt.Med.Review, 5: 196.
17) Castelli D, Colin L, Carnei E, Ries G. (1998). Pretreatment of Skin with a Ginkgo biloba
Extract/Sodium Carboxymethyl-Beta- 1,3-Glucan Formulation Appears to Inhibit the Elicitation of
Allergie Contact Dermatitis in Man, Contaci Dermatitis, 39: 274.
18) Kim SJ, Lim MH, Chun IK, Won YH. (1997). Studies on the Cytotoxic Mechanisms of
Gi nkgetin in a Human Ovarian Adenocarcinoma Celi Line, Biochem.Phannacol., 53: 1244.
19) Scambia G, Almadori G, Maggiano N, Lanza P, Ferlini C, Cattani P, Piantelli M, Ranelletti
FO. (1999). Polyphenols and Cancer Prevention , lntJ.Cancer, 77: 747.
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Inhibitory Effect of Tannins and Flavonoids against the l ,l -Diphenyl-2-picrylhydrazyl Radical,
Biochem Pharmacology, 56: 213.
Suggested for further reading
1) Peterson J , Dwyer J. (1998). Taxonomic classification helps identify flavonoid-containing
foods on a semi-quantitative food frequency questionnaire. JAm.DietetAssoc. 98:682- 5.
2) So FV, Guthrie N, Chambers AF., et al (1996). Inhibition of human breast cancer celi proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices. Nutr. Cancer
26:167- 81.
3) Hirono I , Ueno I , Hosaka S, Takanashi H., et al (1981) . Carcinogenicity examination of quercetin and rutin in ACI rats. Cancer Lett.,13: 15-21.
157
Flavonoids: a Review tor Cosmetic Application
4) Aeschbacher HU, Meier H, Ruch E . (1982). Non-mutagenicity in vivo of the food fla-vonol
quercetin. Nutr.Cancer 2:90.
5) Nishino H , Nishino A, lwashima A., et a1(1984). Quercetin inhibits the action of 12-0-tetradecanoylphorbol-13-acetate, a tumour promoter. Oncology 41:120- 3.
6) Kuo SM. (1996). Anti-proliferative potency of structurally distinct dietary flavonoids on human
colon cancer cells. Cancer Lett., 110:41- 8.
7) Stavric B. (1994). Quercetin in our diet: from potent mutagen to probable anti-carcinogen. Clin.
Biochem. 27:245-8 .
8) Vinson JA, Bose P. (1988). Comparative bioavailability to humans of ascorbic acid alone or in
a citrus extract. Am.J.Clin.Nutr., 48:601-4.
9) Rehn D, Brunnauer H, Diebschlag W, Lehmacher W. (1996). Investigation of the thera-peutic equivalence of different galenica! preparations of 0 -(s-hydroxyethyl)-rutosides following
multiple dose per ora! administration . Arzneim. Forsch. 46:488-92.
10) Bergqvist D, Hallbook T, Lindblad B, Lindhagen A. (1981). A double-blind tria! of 0-(shydroxyethyl)-rutoside in patients with chronic venous insufficiency. Vasa 10:253-60.
11) Unkauf M, Rehn D, Klinger J ., et al (1996). In vestigation of the efficacy of oxerutins compared to placebo in patients with chronic venous insufficiency treated with com-pression stockings. Arzneim. Forsch. Drug Res., 46:478-82.
12) Stegmann W, Hubner K , Deichmann B, Muller B. (1987). Efficacy of 0-(s-hydroxyethyl)rutosides in the treatment of venous leg ulcers. Phlebologie 40: 149- 56 [in French] .
13) Diehm C, Trampisch JH, Lange S, Schmidt C. (1996) . Comparison of Ieg compression stocking and ora! horse-chestnut seed extract therapy in patients with chronic venous insufficiency.
Lancet 347:292-4.
14) Bisler H, Pfeifer R , Pauschinger P. (1986). Wirkung von RoBkastaniensamenextrakt auf die
Transkapillare Filtration bei chronishcer venoser Insuffizienz. Deutsche Med. Wochenschr.,
111:1321-9 [in German].
15) Dartenuc JY, Marache P, Choussat H. (1980). Resistance Capillaire en Geriatrie Etude d' un
Microangioprotecteur. Bordeaux Médical 13:903-7 [in French].
16) Cappelli R, Nicora M, Di Perri T. (1988). Use of extract of Ruscus aculeatus in venous disease in the Iower limbs . Drugs Exp.Clin.Res., 14:277-83.
17) Carvel I, Halperin V. (1961). Therapeutic effect of water soluble bioflavonoids in gingival
inflammatory conditions . Oral Surg ., Oral Med.Oral.Pathol.,14:847-55.
18) Dzink JL, Socransky SS. (1985). Comparati ve in vitro activity of sanguinarine against ora!
microbial isolates . Antimicrob. Agents Chemother., 27(4):663-5.
19) Griffith JQ. (1953). Clinica! application of quercetin: preliminary report. J. Am. Pharm. As-soc.,
42:68-9. (Historically interesting)
20) Shanno RL. (1946). Rutin: a new drug for the treatment of increased capillary fragility. Am. J .
Med.Sci., 211:539-43. (Historically interesting)
21) Piller NB, Morgan RG, Casley-Smith JR. (1988). A double-blind cross over tria! of o-betahydroxyethyl-rutosides (benzopyrones) in the treatment of lymphoedema of the arms and legs.
Br. J. Plast. Surg .,41:20-7.
22) Racz-Kotilla E, Racz G, Solomon A. (1974). The action ofTaraxacum officinale extracts on the
body weight and diuresis of laboratory animals. Pianta . Med., 26:212-7 .
158
E. E.Brand-Garnys, H. Denzer. H. Meijer, H. M.Bran d
23) Doan DD, Nguyen NH, Doan HK., et al (1994). Studies on the indi viduai and combined diuretic effects of fou r Vietnamese traditional herbal remedies (Zea mays, Imperata cylindrica,
Plantago major and Orthosiphon stamineus). J Ethnopharmacol., 36:225- 31.
24) Dini D, Bianchini M, Massa T, Fassio T. (1981). Treatment of upper lymb lymphedema after
mastectomy with escine and levo-thyroxine. Minerva Med.,72:2319-22 [in Italian].
25) Tyler V. (1994). Herbs of Choice: The Therapeutic Use of Phytomedicinals. New York:
Pharmaceutical Products Press, 76-7 [review].
Author Address:
Dr. lr. Hans M. Brand
Elzbieta Cosmetics B.V.
Bronsmos 41
2914 AD Nieuwerkerk a/d IJssel
The Netherlands
Fax +31-180-318164
E-mail: [email protected]
159
J. Appl. Cosmetol. 25, 161-178 (October/December 2007)
NANO-STRUCTURED PRODUCTS: TECHNOLOGY
ANO FUTURE
Pierfrancesco Morganli', Lee Yuanhong2 and Gianluca Morganti'
' Professor of Applied Cosmetic Dermatology, Il University of Naples - ltaly; R&D Director. Mavi Sud s.r. l. Aprilia (LT) - ltaly; Visiting Professor of China Medicai University Shenyang - China; President and
2
Secretary Generai of the lnternational Society of Cosmetic Dermatology -Roma - ltaly
No.1 Hospital of China Medicai University Shenyang(PRC) - China
' Techical Director Mavi Sud s.r.l.- Aprilia (LT) - ltaly
Presented at: the B'h l.S.C.D. Congress: Cosmetic Dermotology from West to Eost: the combined rep/y for o globo/ wellness - October 20-23 Beijing - Chino;
Key words: Nonotechnology; Nonoscience; Nonostructures; Chitin nonofibri/s; Nonoproducts;
Nonotubes;
Summary
Nanotechnology is understood as the characterization , type, production and use of structures and
systems the exact size and shape of which must be measured on a nanometric scale.
For these reasons, the ability to handle selectively materials of nanometric size has led the industry
to develop raw materials with new properties and significant advantages as compared to the macroscopic world.
Thus new products are being designed, or have been designed, which present such innovative features, also in terms of their applications, as to have already influenced our current lifestyle. A case in
point is the wireless telephone !
According to the US National Science Foundation, the global nano-products market will register a
turnover of over 1,000 billion dollars a year in the nex t I 0-15 years !
And the key to the growth of this market will be the development of technology that allows products
with enhanced unique properties and functionality to move from the laboratory to commerciai products.
Nanotechnology will therefore be able to spearhead innovation, giving new impetus to a globalized
and ever faster trade !
In addition to nove) materials, nano-enabled products are also likely to include highly efficient catalysts, supercapacitors, fast charge/discharge high-energy batteries, membranes with nove! permeation
characteristics, and various biometrie structures that could have applications in medicine as well as
security and identification.
161
Nano-structured Products: Technology and Future
But the ability to market nano-structured products will depend on the abi lity of companies to produce and contro] this new class of products, meeting the needs of both man and the environment, on the
ability of govemments to regulate their production and use quickly and effectively, a nd on the ability of the products themselves to meet the needs and expectations of consumers.
Riassunto
Per nanotecnolog ia si inte nde la caratterizzazione, la tipologia, la produzione e l' uso di strutture e
siste mi che richiedano l'esatto controllo della loro dimens ione e della loro forma su scala nanometrica.
Per questi motivi l'abilità di manipolare selettivame nte mate riali di grandezza nanometrica, ha portato l' industria a sviluppare materie prime che posseggono nuove proprietà e vantaggi significati vi se
paragonate al mondo macroscopico.
Si stanno così sviluppando o sono stati sviluppati prodotti talmente innovativi anche per le loro
applicazioni , c he hanno già influe nzato l'attuale nostro modo di vivere.
Ne è un esempio il telefono portatile !
Secondo l'opinione della National Scie nce Foundation degli USA, il mercato mondia le dei nano-prodotti svilupperà un fatturato superiore ai 1.000 miliardi di dollari l'anno, pe r i prossimi 10- 15 anni !
La chiave di volta di questa crescita sarà rappresentata dallo sviluppo della tecnologia capace di dar
luogo alla creazione di nano-prodotti che , unici per le loro caratteristi che e proprietà,
La nanotecnologia sarà, quindi, in grado di guidare l'i nnovazione dando un nuovo impulso ad un
commercio ormai globalizzato e sempre più veloce !
Tra i molti materiali già presenti sul mercato si possono ricordare diversi superconduttori, batterie a
più alta carica energetica e d i maggior durata, me mbrane con caratteri di permeazione più elevata,
oltre a di verse strutture biomedicali o microcircuiti particolari da utili zzare nel campo della sicurezza e per la tutela del marchio
L'abilità a commercializzare i prodotti nanostrutturati dipenderà dalla capac ità delle aziende di produrre e controllare questa nuova classe di prodotti ri spettando le esigenze sia dell ' uomo che dell ' a mbie nte e dalla capacità dei Governi, nel saperne rego lamentare rapidamente ed efficacemente la produzione e l' uso oltre, che dall a capac ità dei prodotti stessi nel soddisfare le necessità e le aspettati ve
dei consumatori .
162
P. Morganti, L. Yuanhong and G. Morganti
WHAT IS NANOTECHNOLOGY
Nanotechnology is understood as the characterization, type, production and use of struc tures
and systems the exact size and shape of which
must be measured on a nanometric scale (1).
N anotechnologies are the set of methods and
techniques for processing matter on an atomic
and molecular scale to create products presenting special and improved chemical-physical
features as compared to conventional ones.
What size is a nanometer (nm)?
A nanometer corresponds to one bill ionth of a
me ter (Fig. 1) .
Considering that a bacte rium measures 1000 nm
and that the distance between two carbon atoms
of an organic molecule is 0.15 nm , one can easi-
ly comprehend how difficult it must be for the
industry to work with such scales !
Nevertheless, it is common knowledge that
nanomaterials present mechanical, optical, c hemical , magnetic or electric prope1ties that are
comple tely different from the raw materiai from
whic h they are generated (2).
INDUSTRY, NANOTECHNOLOGY ANO MARKET
For these reasons, the ability to handle selectively materials of nanometric size has led the industry to develop raw mate rials with new properties and significant advantages as compared to
the macroscopic world.
NANOSIZE
FuUerene
molerule
@
Fullerene
agglomerate
-
~
e~, dendrimers
e .
"" . .
:•:·
Quantum dots
lo
l A
111111 1
I
I
1 nm
Titanium dioxide
1111111
l.l.Lll4
IOOnm
10 nm
_.Jtji,'
ç~<-)
::.~':.:
,\ tom
'!J
Chitin Nanofibril
111111 1
1 µm
I
UJ.J.J.4
lOµm
ll.l.W.j
100
I
Bactel'ium Somatic celi
Hunrnn
Nancy A. Montelro· Rlvlere, Ph.D,ACT, Fellow ATS "Modlfled"
hair
Fig. J The nanometric scale.
163
Nano-structured Products: Technology and Future
Naootechno!oay lnvestments; market orojections
25,000.00
20,000.00
IN.,....., tlttnl•
Il
l S,000.00
IN anOlools
,g
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!'3
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l 0,000.00
S,000.00
o00
I
I
L....
' ""· L....
2002
2003
Suw«. BCC l11t.
i
I
-
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Year
Fig. 2 Nanotechnology investment forecasts.
New products are being designed, or have been
designed , whic h present such innovative features , also in terms of their applications, as to have
already influenced our c urrent lifestyle. A case in
point is the wireless tele phone!
Other examples of innovative nano-products
present on the market are: sunscreens, some plastic materials with higher eco-efficiency, coating
mate rials that are more resistant to corrosion,
and , naturally, microchips for celi phones, etc ..
How large is this market?
Accord ing to the US National Science
Foundation, the global nano-products market
will registe r a tumover of over 1,000 billion dollars a year in the next 10-15 years ! (Fig.2).
THE TECHNOLOGICAL
PLATFORMS
Thanks to current technological know-how, it is
already possible to build differe nt types of nanostructures (DNA, proteins, cells or viruses, etc.)
164
on special chips that can help to better understand the function performed by proteins in cells .
One need only bear in mind that histones are
proteins which the DNA ribbon contained in
every celi winds around (Fig. 3) , and that chromosomes are huge DNA molecules wound up
tidily around the mselves like balls of yarn
(Fig.4). Since a mistake in winding can prevent,
fo r instance, celi reproduction, the simple deregulation of protein activity represents an
essential etiological factor in the pathogenesis of
many diseases .
Thanks to nanotechnology, it is now possible to
modify the chemistry and the topography of the
substratum of celi cultures so as to e nable them
to mime the extracellular matrix, in such a way
that the same signals used by cells in vivo are
released (Fig. 5).
With the use of other technological platforms , it
is possible to obtain thin nanostructured films
organized as nets, capable of providing a huge
surface that is available for interaction with the
skin tissue and the external environment (Fig.6).
99L
·seuois14 punom peddOJM uoqqJJ \>'NO fr ·fJ!.1
uuoB1ovv ·9 puo Buo14uon;.. ·7 ·uuoB1ovv a
Nano-structured Products: Technotogy and Future
F ig.
s The celi with its ontennoe thot send out signols indispensoble to its doily life.
Fig. 6 Nonostructure of chitoson films.
166
P.Morganti, L. Yuanhong and G. Morganti
This was achieved by MAVI with the production
of 240 nm chitin nanofibrils capable of accelerating in a physiological manner the reparation of
damaged skin (Fig. 7) .
CHITIN NANOFIBRILS
Chitin nanofibri ls (Fig. 8), of an average size of
240 nm , can also be used as carriers, since they
can release in a controlled manner active principJes for pharrnacological or cosmetic use, such
as lutein , for instance .
C hiti n is a known natural polyglucoside that is
easily recogn ized a nd hydrolized by the skin 's
cutaneous enzymes, wh ile lutein, a natural oxicarotenoid, is an antioxidant capable of enriching the skin 's antioxidant system. If these two
molecules are properly treated, the complex
resulting from their bonds can surely perform an
interesting protective role on the skin and mucosae. In fact, it is capable of penetrating very easily thrnugh the skin 's layers, if well dosed and
vehicled, without causing toxic side effects and
serving, on the contrary, as an energy deposit
(Fig. 9).
It is interesting to underscore the ease w ith
which these chitin nanofibrils can be included
both in the natural and in the artificial fibers to
generate entirely innovative tissues (Fig. 10).
NANOTECHNOLOGY
ANO DEVELOPMENT
Thi s growth will be determ ined by the development and type of technology capable of generating products which, being unique for their features and properties, wi ll be able to reach the
global market after bei ng developed in a laboratory.
Thus, the d iffe rent technologies, from electronics to optics, from information tec hnoJogy to
biologica! sciences, wh ich are ali geared towards
the creation of products, when nanostructured ,
have generated products so in novative as to be
distributed at world JeveJ in very Jittle time.
Fig. 7 Skin repair through the use of a particular gel containing chitin nanofibrils.
167
B9l
·s1pqyouou u1i!LP 10 uo1i0Jiauad snoauoinosuOJ1 6 ·8!.1
P. Morgonti, L. Yuonhong ond G. Morgonti
Fig. 10 Chitin nanofibrils for innovative tissues.
Nanotechnology will therefore be able to spearhead innovation, giving new impetus to a globalized and ... ever faste r market!
While some metals, such as Ti , Cu, Ni and Sn,
have proven to be more pliable and stronger
when nanostructured, many nano-assembled
products have revealed exceptional efficiency
features . These include many substances used in
catalys is, various superconductors, batteries
with a higher energy charge and longer duration,
membranes with higher permeation features, as
well as some biomedica! structures or particular
microcircuits to be used in the field of security
and for brand protection (3).
INNOVATIVE
NANOTECHNOLOGIES
Some examples of such innovative technologies
are electronic nano-tubes, structures used in
information technology and in many medicai
fields like molecular diagnostics based on nanostructured biosensors (Fig.11), or nanostructures
capable of transporting drugs or active principles
for cosmetic use (4), or polymers used for diagnostic or monitoring purposes, etc. (5) .
Nanotechnology has therefore inspired the development of exceptionally small and low-energy
sensors that have made it possible to create wireless sensors, wh ich are useful in various applications, from CBRNE (the Chemical, Biologica!,
Radiologica!, N uclear and Explosives industry)
to medicai diagnostics.
Furthermore, in the area of security, particular
nano-sensors have been introduced which, inserted in particular systems of fluids , are starting to
be used to protect and alert infrastructures in
case of natural disasters or terrorist-related
events (6) .
169
Nano-structured Products: Technology and Future
EAPSensors
Fonte: D.i.ni lo In Ross i
Miiano, 15-16 Novembre 2006
Fig. 11 EAP sensors designed with Electroactive Polymers.
Also crucial for our growth is the ability to capture, file a nd anal yze a great deal of information.
Thus, the development of these new syste ms of
sensors associateci with the use of state-of-theart information technology will step up our abi1ity to quickly perceive, understand and process
complex messages that are hard to interpret.
MARKETING NANO-STRUCTURED PRODUCTS
The ab ility to market nano-structured products
will depe nd on the abil ity of companies to produce and contro! this new class of products,
meeting the needs of both man and the e nvironment, on the ability of go vemments to regulate
their production and use quickly and effectively,
and on the ability of the products themselves to
meet the needs and expectations of consu mers.
170
That is why it is necessary forali these nano-products to be designed a nd sold in a way that fully
respects the health of consumers and the e nvironment; in other words, they must be bio and
ecocompatible.
In order to reach these objectives, industries
must c reate new plants, investing the necessary
capitai , while governme nts must support adequately and with rapid decisions these industriai
efforts also by introducing new services.
On the other hand, both industries and the Italian
government should significantly increase investments in research and development to keep
pace with more virtuous European countries and
with the US and China. In fact, Ital y must be
more competitive at the intemational leve! to
maintain the leve) of wellbeing reached by its
citizens.
P. Morganti, L. Yuanhong and G. Morganti
RISKS I BENEFITS OF
NANOPRODUCTS
Any production process that generates profit inevitably entai ls risks and benefits.
Naturally, this also applies to ali nanostructured
processes. When assessing the risks/benefits of
these new chemical structures, the products must
be distinguished according to two main categories: nanoderivatives present in nature and manmade ones.
It is therefore necessary to deterrnine whether
they can be absorbed through the skin or rnucous
rnembranes, contro li ing their possible topical
and/or systemic tox icity; needless to say, this
should be done after studying their physical-chemical properties, such as for instance: (a) the
state of distribution of the single nanoparticles;
(b) the state of agglomeration and size of their
crystal structure; (e) the composition and chemical features of the developed surface; (d) the
electrical charges present in their structure; and
(e) their possible porosity.
Synthetic nanostructures include , for instance,
fullerene which, depending on whether or not it
includes OH groups in its st.ructure, displays
cornpletely different chemical/physical properties and behaviours, also developing a different
tendency for transcutaneous penetration .
Another example of a product "created" in the
lab is the carbon nanotube which is also used in
the biomedical field.
These, like other synthetic nanostructures , penetrate inter- or intracutaneously in the conventional way (Fig.12). Trials showed that nanotubes
can be inserted in the keratinocytes at different
levels, remaining intact within biological structures (Fig. 13 and 14).
Fig. 12 Skin penetrotion as a target for studying the possible toxicity of active principles.
171
Nano-structured Products: Technology and Future
.e
..
/~
Fig. 13 Penetration of nanotubes through the skin layers. Detail.
Fig. 14 Penetration of nanotubes through the skin layers. Detail.
A completely different behaviour was observed
in natural nanostructures like chitin nanofibril
(7 ,8) (Fig. 15), which, like polyglucoside, is rapidly catabolized and reduced to glucose and glucosamine by the enzymes of the skin following
the normai catabolic process (9) (Fig .l 6).
172
In fact, these nanofibrils , on which chemicalphysical as well as biological studies have already been conducted, appear to be useful as active
carriers to be employed in cosmetics as well as
in the area of smart bio tissues (10).
P.Morganti, L. Yuanhong and G. Morganti
Fig, 15 Chitin nanofribrils.
---
Chitin
Physiological Solution
Fig, 16 The celi activity carried out by chitin nanofibtrils corresponds perfectly with the activity carried
out by a normai vehicle.
173
Nano-structured Products: Technology and Future
Naturally, in order to be applied to the skin for
pharmaceutical or cosmetic purposes, ali these
nanostructures must be introduced in suitable
vehicles capable of transporting them through ali
the viable cell layers.
It is therefore possible to create macro, micro or
nanoemulsions made up of different sized particles, the shape and size of which must be known
(Fig.17) .
Thus, it is necessary to prove by means of trials
the types and features of the emulsion considered and the size of the paiticles obtained (Fig .
18, 19) following the model, for instance, of
NANOCREAM®by Sinerga (l I ).
In any event, it is important to underscore that
nanotechnolog ies can surely offer new benefits
to society, be a source of new progress and create new jobs, thus improving also the quality of
our !ife.
However, it is necessary for research to dedicate
more resources to assess their safety and determine the impact that nanomaterials will have on
the environment and on health.
Therefore, it is important that Worldwide
Member States foc us their resources on developing the methodologies to be followed, while
industries monitor their products and production
methodologies, verifying the impact they have
on human health and the environment.
To this end , European chemical industries have
actively participated in and supported specific
national
and
international
projects
involving
nanoproducts
(Nanocare
(www.nanopartikel.info/
and
NanoSafe2
(www.nanosafe.org) to verify their potential
effects on man and the environment (J 2).
There are many challenges to be overcome in the
initiatives against and in the ones in favour of the
more or less rapid distribution of nanoproducts
(13) (Fig. 20).
Fig. 17 Copper nano-particles from a microemulsion: contrai of size and dimension.
174
P. Morganti, L. Yuanhong and G. Morganti
Ana....
Results (Nanocream 10% + 1 0% oils)
Mean size=66. 70 nm
Nanoparticles dlstribution
500
450
•
lJ '
1
'00
350
_:m
~
2
.t
250
200
150
100
50
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41
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- .-•
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61
ft
81
.-
....... ...-
-
!t •
~
101
.
...-y·-
121
Fig.18 Characterization of the micelles of a SINERGA nanocream (Nanocream).
~
Results (Nanocream 10% + 1 0% oils)
Fig. 19 Characterization of the micelles of a SINERGA nanocream (Nanocream).
175
Nano-structured Products: Technology and Future
Standard
development
Env1ronment
Health and safety
research
Commerc1a/1zat1on
challenges
~
I Regu1atory I
~
lnterd1sc1phnary
research
( Techrn~I
I
lnve:,tors
I
f lnsurance
lJtJ~tJon
I
( Reoources
l
I
§
"'
JCompetJtJonl
"
E
Gi
I
::!
o
Technology transfer
and commerc1ahzat1on
N~hnology
lnitiative of Emphasis
~
t:
8
ilì
Fig. 20 The commerciai challenges and initiatives typical of nanotechnologies.
CONCLUSIONS
In order to market nanostructured products and
develop the relateci production processes, in the
short term both the industry and governments
shall have to invest on building new infrastructure and utilize venture capitai. On the other
hand, the implementation and long-term success
of nanotechnologies shall depend on a rational,
informed and transparent dialogue among ali the
parties involved, which shall have to try to
understand both the potential for developing a
green and sustainabJe chemistry and the potential negative effects on human health and the
environment that may arise.
Side effects must be reduced and aspects that
may help to improve the effectiveness of the products must be enhanced as much as possible.
The constant and factual collaboration of governments , universities and industries will lead to
organizing new technological platforms and new
176
products capable of enhancing the quality of I ife
of individuals and of society as a whole. This
project is part of the 7th European framework
Programme (FP7) in which platform 4 is devoted entirely to nanotechnologies (Theme 4:
Nanoscience, Nanotechnologies, Materials and
New production technologies) with special projects targeted especially to European SMEs
(Small and Medium-sized companies) (14). This
important opportunity should be seized by presenting research projects financed by the EU
with some 53 billion Euros in the next 6 years.
Another opportunity has been the 8th Congress
of the International Society of Cosmetic
Dermatology (I.S.C.D.) held this year in Beijing
on 20-23 October. This important meeting organized by the Associations of Dermatologists and
Chinese Medicai Doctors has been attended by
the world's leading experts in Derrnatology,
P. Morganti, L. Yuanhong and G. Morganti
Cosmetology and Wellbeing (Fig.21) . Indeed,
many sessions has been dedicateci to Diet
Supplements and special foods, health and leather tissues and, naturally, Cosmeceuticals and
Natural Cosmetics.
In a completely globalized world, it is necessary
now to compete also with the Chinese people,
not onl y in the area of nanotechnologies but in
ali rapidly expanding sectors .
ffi I\ /ili IN /lili ~Hi:l IJè lllìfi.1 ~mf\ ~~
o croh t'r 20·23. 200 7
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Fig. 23 A view of the 8th ISCD lnternational Congress: programme & audience. Beijing. 2007.
Paper Already published on Journal of Plastic Dermatology Newsletter Nanotec lt
177
Nano-structured Products: Techno/ogy and Future
References
1) Morganti P. (2002). Nanoscenza ed efficacia de i prodotti cosmetici Natura e Benessere, 2(n.4):
258 - 260.
2) Kenny JM. (2006). Nanotechnology and intelligent textiles: actual situation and future perspective. In: Atti Congresso Nanoltaltex 2006: le nanotacnologie per il tessile italiano
(www.unipg.it/material) . Milano 15,16 Nov.
3) Gallucci S. (2006). Anticontraffazione e controllo dei mercati grigi: un approccio nanotecnologico. In: Atti Congresso Nanoltaltex 2006: le nanotacnologie per il tessile italiano . (www.singular-id.com) Milano 15,16 Nov.
4) Morganti P. (2007). Proprietà e prospettive d'uso delle nanofibrille di chitina. In: Workshop
CNR dalle Micro alle NanoTecnologie 30-3 l Gennaio (morganti @mavicosmetics.it).
5) De Rossi D. (2006). Tessuti elettronici basati su polimeri elettroattivi : materiali, dispositivi ed
applicazioni. In: Atti Congresso Nanoltaltex 2006: le nanotacnologie per il tessile italiano.
(www.nanotec.it).
6) Zangani D. (2006). Polyfunctional Technical textiles against natural hazards. In: Atti Congresso
Nanoltaltex 2006: le nanotecnologie per il tessile italiano. ([email protected]) .
7) Morganti P, Muzzarelli RAA, Muzzarelli C, Morganti G. (2006). Le nanofibrille di chitina:
una realtà tutta italiana. Cosmetic Technology 9(6): 2 1-25.
8) Muzzarelli RAA, Morganti P, Morganti G, Palombo P, Palombo M, Biagini G, Mattioli
Belmonte M, Giantomassi F, Orlandi F, Muzzarelli C. (2007). Chiti n nanofibrils/chitosan
composites as wou nd medicaments, Carbohydrate Polymers 70: 274-284.
9) Morganti P, Morganti G , Muzzarelli R.A.A and MuzzareJli C . (2007). Chitin nanofibrils: a
natural compound for innovative cosmeceuticals, C&T USA, vol 122, No4: 8 1-88.
10) Morganti P, Muzzarelli RAA, Muzzarelli C. (2006). Multifunctional use of innovative chitin
derivatives for skin care. J. Appl. Cosmetol. 24: 105-114.
11) Guglielmini G. (2006). Evaluating droplet size in nanoemulsions from a nove! emulsifier
system. C&TUSA 121: (n l2) 67-74.
12) CEFIC (2006). Position paper on nanomaterials (www.cefic.org) aoj @cefic.be.
13) Draft Working Document (2006). Theme 4. Nanosciences, nanotechnologies, materia! and new
production technologies -NMP, October 11 .
Author Address:
Pierfrancesco Morganti Ph.D.
R & D Director
Mavi sud S.r.l.
Viale dell'Industria l
04011 Aprilia (LT) - ITALY
Fax: +39 06 92 81 523
Email: [email protected]
Email: [email protected]
178
J. Appl. Cosmetol. 25, 179-180 (October/December 2007)
lndex Volume
lndex to Volume 25, 2007
Contents:
Hair Growth Stimulators and Inhibitors
S. Krus, K. Pytkowska, J.A rct
Book Reviews
59
Skin care in atopic dermatitis
Biofunctional Textiles and the Skin
K. Pytkowska, S. Majewski
U.C. Hi pler and P. Elsner
85
31
Circadian Physiology. 2nd Edition
Flavonoids: a Review for Cosmetic Application.
Part I
R. Refinetti
Elzbieta E. Brand-Garnys, Horst Denzer, Hamke Meijer,
75
Ha ns M. Brand
93
Metabonomics in Toxicity Assessment
D.G. Robe11son, J. Lindon , J .K. Nicho lson and E. Holmes
79
Flavonoids: a Review fo r Cosmetic Application.
Part Two
Elzbieta E.Brand-Garnys, Horst Denzer, Hamke Meijer,
Enhancement In Drug Deli very
Hans M.Brand
E. Touitou and B.W. Barry
145
121
Ski n Protection
Na no-stru ctured Products: Technology and
Future
S. Schliemann and P. Elsner
P. Morganti, L. Yuanhong and G. Morganti
128
161
Guest Editoria!
Originai Laboratory Studies
Teg ument fro m Unicell ular Organisms to
Mammals
Development of Sensory Methods for Skin
Diagnosis
E. Lenzi Veggetti
M.E. Parente,G. Ares, A. Gambaro
11
39
Generai Articles
SIRT l , the human homologue of the yeast longevity gene, Sir2, is expressed in human skin.
Histological studies
Cosmetic Delivery: Are We Crossing the Final
Barrier Into Dermatology?
Domloge
J .W. Wiechers
133
A. Perrin, E. Bauza,C. Gondran, I. lmbert, C. Dal Farra, N.
1
179
lndex Volume
Special Reports
Ali for Cosmetics: a Warsaw-meeting for innovative skin-care products
P. Morganti
25
Where Nutriceuticals Meet Cosmeceuticals
P. Morganti
111
180
J. Appl. Cosmetol. 25, 181 (October/December 2007)
Abstrats Autor lndex
Author lndex
Arct, J., see K.rus, S., 39
Ares , G., see Parente, M. E., 39
Bauza, E., see Perrin , A ., 133
Brand-Garnys, Elzbieta E., Flavonoids: a
Review for Cosmetic Application. Part I , 93;
Flavonoids: a Review for Cosmetic Application.
Part Two, 145
Dal Farra, C., see Perrin , A., 133
Denzer, H., see Brand-Garnys, Elzbieta E., 93;
see Brand-Garnys, Elzbieta E ., 145
Domloge, N., see Perrin, A., 133
Gambaro, A., see Parente, M. E ., 39
Gondran, C., see Perrin , A. , 133
Imbert, I., see Perrin , A., 133
Krus , S., Hair Growth Stimulators and
Inhibitors, 59
M.Brand, H ., see Brand-Garnys, Elzbieta E .,
93; see Brand-Garnys, Elzbieta E. , 145
Majewski, S., see Pytkowska , K., 85
Meijer, H., see Brand-Garnys, Elzbieta E. , 93;
see Brand-Garnys, Elzbieta E., 145
Morganti, G., see Morganti P. , 161
Morganti, P., Ali for Cosmetics: a
Warsaw-meeting for innovati ve skin-care prod ucts, 25 ; Where Nutriceutical s Meet
Cosmeceuticals, 111; Nano-structured Products:
Technology and Future, 161
Parente, M . E., Development of Sensory
Methods for Skin Diagnosis, 39
Perrin, A., SIRT l , the human homologue of the
yeast longevity gene, Sir2, is expressed in
human skin. Histological studies, 133
Pytkowska, K., see Krus, S., 39; Skin care in
atopic dermatitis, 85
Veggetti Lenzi, E., Tegument from Unicellular
Organisms to Mammals, 11
Wiechers, J.W., Cosmetic Delivery: Are We
Crossing the Final Barrier Into Dermatology?, 1
Yuanhong, L., see Morganti P., 161
181
J. Appl. Cosmetol. 25, 182-184 (October/December 2007)
Subject lndex
a reductase, 64
Aesculus hippocastanum, composition of, 152
Allergens, occupational, 129
Alopecia, androgenetic , 63; areata, 67
Amaranth, acti vity of, 150
Amphibians, 20
Anagen, hair, 63
Antocyanidins, as a antioxidant compounds,
104
Antocyanins, as a antioxidant compounds, 104
Apigenin, antiageing compound, 96
Aristotele, 22
Arthropods, exoskeleton, 16
Atopic dermatitis, 31 , 85; and skin barrier, 87;
and therapy, 88
Bacteria, skin pathogenic, 32; dimension , 163
Baicalin, as a lipoxygenase inhibition , 97, 146
Beauty, from inside, 115
Bergapten, 8-methoxypsoralen, 108
Biomarkers, 79
Biotechnology, new, 35
Birds,21
Botanicals, 33
Buccal, drugs absorption, 123
Calendula officinalis, and its antiinflamatory
activity, 152
Catagen, hair, 63
Ca thelicidins, in keratinocytes, 32
Celi, senescence, 136; somatic, 163
Chamomile, anti-inflammatory acti vity of, 149
Chemistry, search and development, 36
Chitin nanofibril, 167; wound healing activity
of, 167; transcutaneos penetration of, 168
Chitosan, filmed of, 166
Chromons, 105
Chromotherapeutics, to prevent diseases, 78
Circadian, rhythms, 75; mechanisms of, 76
CNS , drugs absorption, 127
Coelenterates, 14
Copper, nanoparticles , 175
182
Subject lndex
Cosmeceuticals, the evolution of health concept, 111
Cosmetic chemists, Polish Society meeting, 25
Cosmetic, delivery, 1; formulation, 5; what is a,
9; a Warsaw - meeting, 25; global market, 25;
EU market, 26; Asia Pacific market, 27; north
American market, 28; Latin American market,
28; emollient activity of, 31; nanoemulsion, 31
Cosmetology, and dermatology acti vities may
be distinguished?, 1
Darwin, Charles, 22
Delivery, skin, 5; enhancement in drug, 121
Dendrimers, dimension, 161
Dermatology, and cosmetology activities may
be distinguished?, 1
DHT, acti vity, 64
DNA, ribbon, 164
Dosing, conditions of acti ve compounds, 7
Drug, delivery, 1; what is a, 9; buccal absorption of, 123; transdermal delivery of, 124
Echinoderms, 19
Ecotoxicology, 79
Efficacy, factors affecting cl inicaJly, 8
Elasticity, clinical evaluation of skin , 48
Emollient, compounds in atopic dermatiti s, 88
Evolution, skin , 11
Fiber, silver, 37
Fibroblasts, human, 136
Filipendula ulmaria, extract, 32
Flavanones, characteri zation of, 103
Flavonoids, as a bioactive substances, 93; 98;
cosmetics applications of, 145; biosynthesis of,
146; function ality of, 147
Fullerene, molecule, 163
Gastrointestinal, drugs absorption, 121
Genkwanin, 95
Ginkgo biloba, antiaging acti vity of, 151
Glabradine, the flavonoid, 152
Glycirrhiza, glabra, 152
Hair, growth stimul ators , 59; cycle , 62
Hirsutism, 68
Homeostasis, physiological, 76
Subject lndex
pH, instrumental measurement of skin, 48
Horse chestnut, composition of, 152
HPLC , 81
Fhotocarcinogenesis, 129
Hydration, instrumental measurement of skin, Phyto-estrogens, in skin ageing, 101
48
Pleasure, the mystery of, 116
Polymers, electroactive, 170
Imperatorio, 8-isopre nylpsoralen, 107
Protein, deregulation , 164
lsoflavones, activity, 101
Jet-Iag, regulation, 77
Proteomics, 79
Khella, vasoprotective acti vity of, 150
Protozoa, 12
PUFA, in atopic dermatitis, 89
Khelline, 108
Quercetin, 99; 146
Licorice, whitening activity of, 152
Lightness, cli nica! evaluation of skin , 48
REACH, to regulate the c hemicals, 84
Linneo, Cari von, 22
Rectal, drugs absorption , 123
Lutein, the outside and inside activity of, 114
Reptilians, 20
Medusas, 14
Rutin, 146
Melatonin, acti vity, 75
Sebum, instrumental measurement of skin , 48
Metabonomics, to study target organ toxicity, Shellfish, chitin from , 168
82
Silver, nanoparticles, 36
Mollusc, terrestri al, 17
Skin, condition of the, 3; penetration, 3; ingredient barrier function of, 4; evolution, 11; care ,
Morin, 146
Myricetin, 146
25; care consumption pro capita, 29; a nd biofunctional textiles, 35; diagnosis, 39; smoothNanocream, SINERGA, 175
ness evaluation, 48; lightness evaluation , 48;
Nanoderivatives, risk/be nefits of, 171
Nano-science, 161
elasticity, 48; self evaluation and clinica! evaluation, 55; protection , 128; 130; barrier, 132;
Nano-sensoring, 169
repair, 167
Nanosize, 163
Nanotechnology, 161; market projections, 164; Sledesta, the satiety activity of, 115
challenges, 177
Smoothness, clinica! evaluation of skin, 48
Nanotube, toxicological aspects of, 173
Sponges, 13
Narigenin, chalcone, 94
Stimuli, photic and non-photic, 76
Stratum corneum, lipid bilayers, 31
Nasal, drugs absorption, 125
Stress, immunoistochemistry of, 135; protective
NMR, spectroscopy, 80
Nutriceuticals, the evolution of, 111; safety of, role of sirti in , 142
113; the market, 118
Sulfuretin, 99
Obesity, the problem of, 116
Sunsceens, the most widely used , 30
Tacrolimus, in atopic de rmatitis, 88
Octopus, colonie, 14
Tegument, as the end of organism, 11
Ocular, absorption of drugs, 126
Organism, evolution , 11
Telogen, hair, 63; effluvium , 68
Otc, delivery, 1; what is a, 9
Testosterone, metabolic path , 64
Penetrant, physiochemical characteristics of Textiles and skin, 35; bio-functionality of, 35;
the, 4; hydrophilic , 7; lipophilic, 7
antimicrobica! activity of, 36; electronic, 36;
Penetration, factors affecting skin, 3
innovative, 168
Peptides, antimicrobial, 32
Tornato, in the Mediterranean diet, 117
183
Subject lndex
Toxicants, occupational , 129
Toxicity, tests, 83
Transdermal, drug delivery, 124
Trascriptomics, 79
Uterus, drugs absorption, 125
UV, blocking, 33
Uvb, irradiation, 32
Vagina, drugs absorption, 125
Vertebrates, fishes, 19
Visnadin, 151
Vinsaga vera, vasoprotective activity of, 150
Wellness, the evolution of health , 111
Wrinkles, skin evaluation of, 48
Yeast, longevity gene sir, 133
184
Announcement
/1&.I
••• •• ••••• l• •• •11t•••• • L.. ••••••••
APOPTOSIS WORLD 2008
From mechanisms to applications
January 23 - 26, 2008
Contact: Dr. Mare Diederich
Fondation Recherche sur le Cancer et !es Maladies du Sang
Laboratoire de Biologie Moleculaire
et Cellulaire du Cancer (LBMCC)
Hopital Kirchberg
9, rue Edward Steichen
L-2540 Luxembourg
Phone: +352 2468-4040
Fax: + 352 2468-4060
Email: [email protected]
MSN: [email protected]
Skyp : marc_diederich
Meeting information: http://www.transduction-meeting.lu
Lab/Seminar information: http://www.lbmcc .lu
XIX
Announcement
Baltic Association of Dermatovenerologists
INTERNATIONAL CONFERENCE
June 20-21;2008, RIGA LATVIA
For information:
A ndris Y.Rubins,MD,Prof & Chrm
Riga Stradins University
Kr. Valdemara Street 76-75
Riga,LV 1013,
LATVIA
phone: 00371 29481725
fax
00371 67361615
Email: [email protected]
Website: www.badv.lv
xx
IXX
AGV3
+uawa:Junouuv
Announcement
Contact information
Symposium Secretariat
Prof. Nilsel ilter
Ayazmaderesi Cad. Karadut Sok. No:7
34394 Dikilita~- ISTANBUL - TURKEY
Phone : + 90 212 258 60 20
Fax : + 90 212 258 60 78
e-mail : [email protected]
[email protected]
Congress Secretariat
Figiir Congress & Organisation Services
Ayazmaderesi Caddesi Karadut Sokak No 7
34394 Dikilita~ I Istanbul
Phone : + 90 212 258 60 20
Fax : + 90 212 258 60 78
e-mail : [email protected]
For Registration
: [email protected]
For Abstract Submission: [email protected]
: [email protected]
For Sponsorship
For Hotel Reservation : [email protected]
: [email protected]
For Exhibition
Symposium website
www.eadv.org/istanbul2008
Dates to Remember
Abstract Submission Deadline
: 1December, 2007
Abstract Evaluation Announcement : 1February, 2008
Reduced Registration Deadline
: 14 January, 2008
.,
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Announcement
Università
degli Studi di Pavia
Facoltà di Medicina
e Chirurgia
Anni accademici
2007-08, 2008-09
Che cos'è
Un corso di alta formazione post-laurea
istituito ai sensi del D.M. n. 270 del
22/10/ 2004 per il conseguimento del Diploma
Universitario di Master in Medicina Estetica e
del Benessere, titolo di studio accademico con
valore legale.
Un percorso di studio intensivo teoricopratico per formare il Medico Estetico, figura
professionale destinata all'attività in studi
autonomi, centri polispecialistici, centribenessere, palestre, beauty farms e stazioni
termali.
Due anni di lavoro full-time, armoniosamente
articolato tra lezioni teoriche, attivit à
pratiche e stages presso aziende di settore.
Requisiti fondamentali per l'ammissione
Laurea in Medicina e Chirurgia
Abilitazione all' esercizio della professione di Medico
Chirurgo
Iscrizione all'Ordine dei Medici Chirurghi
Numero massimo iscritti: 30
L'ammissione è determinata da una selezione secondo
graduatoria di merito.
Per i criteri di ammissione consulta il sito
www.plasticaticinensis.it
Obiettivi e Durata
Conseguimento del Diploma Universitario di Master in
Medicina Estetica e del Benessere.
Monte ore di 1500/ anno così ripartito:
• 480 h/anno di didattica frontale
• 300 h/anno di stage e tirocini pratici
• 720 h/anno di studio individuale
Percorso Didattico
• Materiale didattico.
• Transfer e soggiorno all-inclusive nelle località di stage
fuori sede.
• Lunch di lavoro.
Previste formule agevolate di soggiorno in Pavia per gli
studenti fuori sede.
Finanziamento personalizzato:
La Banca Regionale Europea mette a disposizione un
finanziamento a tasso agevolato per coprire il cost o
dell 'iscrizione.
\
/
1
Domande di ammissione
Emissione del bando:
24 Settembre 2007
Termine ultimo per le domande
di ammissione:
1O Dicembre 2007 alle ore 12
Per il bando consulta il sito
www.plasticaticinensis.it
Il percorso didattico si articola in 9 moduli di
insegnamento ed in attività di tirocinio pratico:
• Aspetti generali della Medicina Estetica e del
Benessere
e discipline propedeutiche
Dermatologia e Cosmetologia
• Termalismo
Flebolinfologia
Cura della silohuette
• Tecniche e metodiche in Medicina Estetica e del
Benessere
• Apparecchiature e tecnologie di specifico impiego in
Medicina Estetica e del Benessere
Attività motorie
Terapie complementari e non convenzionali
• Tirocinio-Stage
Costo di iscrizione
Il costo di iscrizione al Master in Medicina Estetica e del
Benessere è di 6000€/anno formula all-lnclusive.
Il costo di iscrizione comprende:
• Frequenza di tutti i corsi teorici e delle attività
pratiche.
xxv
Announcement
Master Universitario biennale di II livello in
MEDICINA ESTETICA E DEL BENESSERE
dell'Università di Pavia per gli anni 2008-2009:
un prodotto formativo aggiornato e completo,
una formula organizzativa d'avanguardia,
nella lunga tradizione di un grande Ateneo.
IL MASTER biennale DI II LIVELLO IN MEDICINA ESTETICA E DEL BENESSERE
dell'Università di Pavia viene riproposto per gli anni accademici 2007-2008, 2008-2009, in considerazione dei lusinghieri risultati formativi della precedente edizione, ora in via di conclusione.
OBIETTIVI: opportunità di formazione professionale qualificata e di rapido inserimento nel mondo
del lavoro per laureati in Medicina e Chirurgia in una società in cui la Medicina del benessere non è
più un privilegio per pochi ma un 'esigenza per tutti.
METODI: Lezioni intensive, attività pratica garantita per ciascun allievo (hands-on) , stages presso
ambulatori polispecialistici, centri-benessere, palestre, beauty farms, stazioni termali per la formazione del Medico Estetico.
COSTI: Grazie alla formula ALL-INCLUSIVE, il costo di iscrizione di 6000€/anno comprende la
freq uenza di tutti i corsi teorici e delle attività pratiche, il materiale didattico (testi scolastici , dispense, audio-video), il trasferimento alle sedi distaccate in Pavia e dintorni, il lunch di lavoro giornaliero in Pavia, il trasferimento ed il soggiorno con pensione completa nelle località di tirocinio-stage
fuori sede. Sono inoltre previste fo rmule agevolate di soggiorno in Pavia per gli studenti non residenti. Nessun pensiero superfluo deve turbare l'apprendimento dell'arte della Medicina Estetica e
del benessere a Pavia !
La Banca Regionale Europea mette inoltre a disposizione un comodo finanziamento a 5 anni a tasso
agevolato per coprire l'intero costo d'iscrizione. Una ragione in più per non avere preoccupazioni
inutili e preparare con tranquillità il proprio futuro professionale.
NUMERO CHIUSO di massimo 30 iscritti .
DEADLINE: Le iscrizioni si chiudono alle ore 12.00 del 10 dicembre 2007.
OPPORTUNITA' : E' fi nanziata 1 Borsa di Studio a copertura delle spese di iscrizione per il miglior
classificato .
PER INFORMAZIONI: www.plasticaticinensis.it
MAIL: [email protected]
BANDO DI CONCORSO: http://www.unipv.it/webesami/post.htm
FINANZIAMENTO a tasso agevolato: www.brebanca.it
XXVI
Announcement
The Master Degree in Aesthetic and Wellness Medicine of the
University of Pavia: new edition (2008-2009).
GOALS : The new edition of the Master Degree in Aesthetic and Wellness Medicine of the
Uni versity of Pavia is established fo r the years 2008 and 2009. lt is a great opportun ity of professio nal training for Medicai Doctors: trained doctors in the now-ending successful past edition of the
Master are already employed in this new field of health sciences, as aesthetic & wellness Medic ine
no longer is a pri vilege for few but a need fo r everybody.
METHODS: Two years full-time intensive courses and hands-on training in cosmetic medicine &
wellness centres, companies, labs, spa, beauty farms and gyms .
FEE: With the new ALL-INCLUSIVE package the registration fee (6000€ /year) includes: intensive
lessons, courses and serninars, text books & audio-video support, transfer to satell ite centres, lunch
breaks, transfer & full board accommodation in the partner centres away from Pav ia .
Accommodation facilities available fo r non resident students in Pavia.
No extra concems while mastering the art of aesthetic and wellness medicine in Pavia!
Five years low interest persona! loans by Banca Regionale Europea: one more reason to pian your
professional future with no worries .
NUMERUS CLAUSUS: Registration limited to a maximum of 30.
DEADLINE December the 10'" 2007 , 12.00 noon.
NEWS: The registration fee is supported by a grant for the I " best appliant.
INFORMATIONS: www.plasticaticinensis.it
MAIL: info@plasticaticinensis .it
ANNOUNCEMENT: http://www.unipv.it/ webesami/post.htm
PERSONAL LOANS: www.brebanca.it
XXVII
In copertina I Front cover
Lamine di chitosano (Hydagen HCMF) per tissue engineering al microscopio elettronico a scansione (SEM). Su gentile concessione de lla Prof.ssa Graziella Biagini , I stituto di Morfologia
Umana Normale, Università Politecnica delle Marche, Ancona, Italia
Scanni ng electron microscopy (SEM) immage of chitosan structures (Hydagen HCMF) for tissue
engineering applications On kind permission of Prof. Graziella Biagini , Istituto di Morfologia Umana Normale, Università Politecnica delle Marche, Ancona- Italy
Chiuso in tipografia: Dicembre 2007
Journal of Applied Cosmetology published quarterly by INTERNATIONAL EDIEMME , Via Innocenzo XI, 4 1
00165 Roma, ltaly. Direttore responsabile: P. Morganti. Direzione, Redazione ed Amministrazione: Via Innocenzo
XI, 4 1 - 00 165 Roma, ltaly. Impaginazione e Stampa: Grafica Flaminia, Roma. Copertina: Dr P. Morganti - Roma
Italy - Sped. abb . Postale Comma 34 art. 2 Legge 549/95 Roma. Aut . del Trib. di Roma n. 3173/83 del 8-7-83 .
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epitelio vulvare con flogosi
vulvar epithelium with phlogosis
FERENCES:
J arrett A . (1986) Ageing ot the Mucous Membranes, Cosmetic Dermato/ogy, Voi. 2, Ed. by P. Morganli, F.J.G. Ebling, RomeB r uno I, Fischetti C, lnghirami P, Senatori R, Bacicalupi A. (1991} C02 laser surgery ot the lower genital traci in women:
ulls ot post operative treatment with vitamin A+E gelatin mixture J. Appl. Cosmetol., 9, 73-76 - 3) - Morganti P, Lanzone A,
eri L. (1998) A new diffusion system through the mucous membranes, skin and hair, J. App/. Cosmeto/., 16, 45-50 - 4) en.ano Ferraris AM, Morganti P. (1999) Essentisi tatty acids tor the epidermal barrier homeostasis : stability and satety., C &
Vorldwide, 8, 32-34 - 5) - Cornelli U. (2000) Fluid diffusion System in the treatment ot aging mucous membranes, In: New
nds in Cosmetic Science, Conterence Proceedings, Verlag, H. Ziolkowsky GmbH, pp. 44-50 -6) - Beyer N, D riller H, BUnger
2000) Ectoin an innovative, multitunctional active substance tor the cosmetic industry, SOFW- Joumal, 126, 26-29 - 7) ~ lana F, Dionisi e , Lippa P, Ronca S. (2003) Fisiologia e Omeostasi del distretto vulvo-vestibolo-vaginale, In Trattato di
elogia Vulvare, voi. I, pag.47-60, SEE-Firenze
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References
clinical/y carrect cosmetics
1-Muscardin L, Morganti P, Tartarini S, Valenzano L. (1976) Valutazione clinica dell'azione antiforforale e sebostatica di tensidi cationici associati alla zinca piritione, Chron.
Derrn., 7:659-666 ·2- Morganti P., (1999) Uv and Hair Weathering. Eurocosmetics 9: 30-32 -3- Morgantl P., Morganti G., (2001 ) Hair and Cosmesis , Soap & Cosmetics, 77
(n.9): 26-31-4- Sunonen R.E., Oawber P.R. and Ellls D.H. (1999) Fungal infections in the skin, hair and nails, p.120 . 5· Morganti P., Fabrizi G. (1999) Safety evaluation of
phytosphingosine and ceramides of pharmaceutical grade, J . Appt. Cosmetol., 17: 1-9 - 6-Cassano N, Amoroso A , Vena GA (2002) Zinc nutritive and skin: an overview, J. App/,
Cosmetol., 20: 183-194 ·7- Frydrych A., Arct J , Kasiura K. (2004) Zinc. A criticai importance element in Cosmetology, J. Appl. Cosmetol., 22: 1-13 -8- COLIPA n. P81 (2002)
Opinion Conceming Zlnc Pyrithione , SCCNFP/0671103/Final
www.mavicosmetics.it
Mavì Sud srl - V.le dell'Industria, 1 - 04011 Aprilia (LT) Tel. 06.9286261 - Fax. 06.9281523
[email protected]