REGU®-FADE - Cosmetics Online

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The Personal Care division of DSM Nutritional Products is the world’s leading supplier of
vitamins, bio-active ingredients and UV filters to the cosmetics industry. Since our merger
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complete and modern portfolio of services and products for sun, skin and hair care. The
brand Pentapharm forms our innovative portfolio of active ingredients for skin care. Every
product comes with claim substantiation and an extensive product dossier, including
safety aspects and in vivo as well in vitro studies.
We offer innovative ingredients produced by means of peptide synthesis, extraction of
­natural substances and biotechnology. Our ALPAFLOR® product line extends our port­folio
in the broad field of natural substances; following strict organic rules, the developed
high-quality extracts are certified by Ecocert® and Natrue as raw materials for natural and
organic cosmetics.
Our knowledge and years of experience in marketing and claim substantiation, our
­comprehensive support in formulation and application, and our regulatory expertise,
together with a global distribution network, enable us to best meet our customers’ needs.
For more information, please visit us online
at www.dsmnutritionalproducts.com
Europe
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Switzerland
Phone: +41 61 815 8888
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+41 61 815 8880
Email:info.dnp@dsm.com
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P0007 © DSM Nutritional Products Ltd. 2011
REGU®-FADE
The most effective solution for
noticeably brighter skin
• Anti-aging skin care products for more even skin tone
Suggested concentration
• Up to 1% REGU -FADE in cosmetic formulations
®
INCI name
• Resveratrol
Structure
• trans-Resveratrol (molecular weight: 228.25 g/mol)
3 | Melanosome1°function and maturation
REGU -FADE also affects the function and maturation of melanosomes
Vehicle
REGU®-FADE 0.2%
by reducing SLC24A5 (-39%) and SLC45A2 (-74%)REGU
gene
expression
levels.
®
Ascorbyl glucoside 2%
-FADE 1%
®
40
60
80
REGU®-FADE attenuates melanosome transport within melanocytes,
* p ≤ 0.05 vs. vehicle
Days
shown by the reduction of the MYO5A (-55 %) and MREG (-69 %) gene
expression levels, as well as melanosome transport to keratinocytes,
shown by the reduction of RAB 27A (-24%) gene expression levels.
8°
5 | Melanin synthesis
REGU -FADE reduces the conversion of tyrosine into eumelanin or
6° points, shown by the downregulation of OCA2
pheomelanin at various
(-37%), TYR (tyrosinase) (-31%), DCT (-85%) and TRP1 (-63%) gene
expression levels.
-40
-40
6° -6060%
-60
Long-term study
EC50=~60µM
EC50=~100µM
A double-blind, placebo-controlled
study was performed on
52 Indian
0.0014%
-80
-80
female
volunteers. Per test area
a cream (SPF ~10) plus test substance
40%
-100
-100
was applied
forearms.TYRP1
Colorimetric
SILV twice daily
OCA2 on theTYR
DCTmeasurements
MC1R
4°
20%
were performed after 14, 28, 60 and 90 days respectively.
*
Melanin Biosynthesis
Melano®genesis
10%
Significant
skin brightening
M O R E with
P O T 1%
E N TREGU -FADE
2°
0
0 3°
1
10
100
Vehicle
* p ≤ 0.05 vs. vehicle
2°
1°
*
0
0
20
Vehicle
REGU®-FADE 0.2%
REGU®-FADE 1%
Ascorbyl glucoside 2%
40
60
80
* p ≤ 0.05 vs. vehicle
REGU®-FADE 1%
* p ≤ 0.05 vs. vehicle
6°
*
4°
2°
0
Vehicle
Ascorbyl glucoside 2%
REGU®-FADE 1%
72 hours
48 hours
40%
20%
1°
Brightening
% melanin production
MC1R
*
1000
100
log c (substance) [µM]
Control
-100
100 µM PTU
Vehicle
µM 0.2%
-FADE
REGU®44
A double-blind, placebo-controlled study was performed on 12 Caucasian
POSITIVE
REGU®glucoside
NEGATIVE
-FADE
REGU®-FADE
2%
1%
volunteers. Per testCONTROL
area creams
were
applied
3 Ascorbyl
times
per day on
the
CONTROL
(0.001%)
0
forearm.
Colorimetric measurements were performed after 14 days.
0
20
40
60
80
* p ≤in
0.05
vehicle
Days
and significant skin
brightening
2 vs.
weeks
Visible
with 1% REGU®-FADE
100%
8°
REGU®-FADE
Kojic acid
80%
6°60%
EC50=~60µM
0.0014%
40%
EC50=~100µM
*
4°
20%
10%
MORE POTENT
2°
0
20%
Melanogenesis
10
Short-term
study
0
0
% melanin production
24 hours
72 hours
48 hours
24 hours
72 hours
48 hours
24 hours
% melanin production
Cell lightening
60%
2°
1000
*
log glucoside
c (substance)
Ascorbyl
2% [µM]
REGU®-FADE 1%
40%
0
1
10
Vehicle
100
log c (substance) [µM]
Ascorbyl glucoside 2%
1000
REGU®-FADE 1%
* p ≤ 0.05 vs. vehicle
100%
% melanin production
In-20vivo
80%
REGU®-FADE
Kojic acid -20
8°
Ascorbyl glucoside 2%
Lighter skin
0
2°
Vehicle
72 hours
20
Days
0
40
60%
MORE POTENT
80%
* p ≤ 0.05 vs. vehicle
100%
0
10%
60
118µM AscHlc
-40
Lighter skin
Days
88µM REGU®-FADE
DCT
72 hours
Human Melanocytes
TYRP1
Melanin Biosynthesis
20%
0
80
80
-20
80%
EC50=~100µM -80
48 hours
60
SILV
EC50=~60µM
0.0014%
OCA2
TYR
24 hours
40
40
-60
100% 1
3°
Timepoint: 72 hours
20
-4080%
-60
60%
-80
72 hours
Tissue:
REGU®-FADE
Kojic acid
48 hours
40
20
with higher
0
24 hours
Tissue:
8°
®
4°
60
60
Darker skin
REGU -FADE decreases KIT (=stem cell factor receptor) gene expression
to 58% in melanocytes which additionally reduces melanin synthesis.
®
20
0
100%
-20
100%
80
20
72 hours
*
2 | KIT signalling
2°
0
40
REGU
Timepoint: 72 hours
activity
20 than kojic acid.
48 hours
REGU®-FADE downregulates the MCR1 (α-MSH receptor) expression
level to 49% in melanocytes, leading to decreased expression of
3°
MITF-related genes such as TYR (tyrosinase), TRP1, DCT, SILV and OCA2
which reduces melanin synthesis.
0 80
0
Melanogenesis
REGU®-FADE
(0.001%)
24 hours
MC1R
1 | α-MSH signalling
4 | Melanosome0transport
Vehicle
0.2%-FADE
REGU -FADE
NEGATIVE
POSITIVE
REGU
CONTROL
CONTROL
(0.001%)
REGU®-FADE 1%
Ascorbyl glucoside
2%
®
44 µM
POSITIVE
CONTROL
Tissue:
REGU®-FADE
AscHlc
-FADE
(0.0014%)88µM
decreases
melanin118µM
production
Cell lightening
DCT
44 µM
®
100 µM PTU
®
∆ ITA°
TYRP1
-100
100 µM PTU
Control
NEGATIVE
CONTROL
60
Tissue:
Human
Melanocytes
Melanin
assay on
normal
human melanocytes
% melanin production
TYR
80
∆ ITA°
Melanocyte
OCA2
Control
-80
MITF gene
SILV
0
1°
20%
Darker skin
-60
CREB
20%
48 hours
-40
MITF
40%
-10040%
24 hours
-20
MITF
40%
72 hours
MITF
degradation
2°
0
48 hours
20
60%
24 hours
40
*
80%
72 hours
118µM AscHlc
3°
60%
Tanning
Brightening
60
Keratinocyte
MITF
MC1R
100%
48 hours
2.
DCT
80%
0
% melanin production
• Creams and serums for age spots
-100
In vitro
Lighter skin
• Skin brightening facial and body care products
-100
Darker skin
Cosmetic application
-80
∆ ITA°
• Multi-target mechanism
-80
∆ ITA°
• Nature identical pure trans-resveratrol for more
effective and even skin brightening
-60
80
4.
∆ ITA°
• Visibly brighter skin in 2 weeks
-60
24 hours
MREG
Melanin Biosynthesis
reduced expression
∆ ITA°
Benefits
-40
RAB27A
Effect of REGU-FADE:
Key facts
-20
Cell lightening
MYO5A
88µM REGU®-FADE
Adenylate
-100
-20
-40
0
Low concentrationMelanin
REGU Biosynthesis
-FADE (0.001%) leads to a 50%Melanoreduction
genesis
of melanin content.
Human Kit
MelanocytesSCF
cyclase
-40
-80
Efficacy
% melanin production
1.
-20
-60
cAMP
Timepoint: 72 hours
% melanin production
Brightening
TYR
Melanogenic
Enzyme
Expression
MC1R
REGU®-FADE has proven its outstanding efficacy in human clinical
trials with visible effects in only 2 weeks. Compared with a market
benchmark, REGU®-FADE worked faster early on and reduced the
production of melanin more effectively throughout the studies. DSM
scientists showed that REGU®-FADE attenuates skin pigmentation via
multiple mechanisms, from initial signaling and gene expression to
melanin production and final melanosome transfer.
40
®
MAPK
0
118µM AscHlc
SILV
OCA2 on B16F10
TYR
TYRP1
Melanin
assay
cells
Timepoint: 72 hours
20
88µM REGU®-FADE
20
∆ ITA°
Tanning
SILV
Tissue:
40
α-MSH
Tissue:
SLC45A2
TRP1
5.
OCA2
60
Human Melanocytes
∆ ITA°
Melanosome
DCT
60
Tissue:
Tanning
80
Tissue:
40
Brightening
3. SLC24A5
REGU®-FADE is high-performing and fast-acting. It uses pure natureidentical trans-reservatrol that is free from pesticides and emodin,
addressing high consumer awareness about safety and visible effects.
Resveratrol is a known potent antioxidant found in red grapes and
associated with various health benefits.
60
0
Skin pigmentation involves many genes at various steps. A gene
expression test (RT-PCR) has been performed and showed that
REGU®-FADE (0.002%) is very effective in attenuating the melanin
production cascade at multiple points.
100%
80
20
Lighter skin
Skin brightening is one of the fastest growing segments in the
cosmetic industry. In Asia skin brighteners are widely used
to make skin fairer. In Western countries consumers want to
diminish age spots, reduce excessive pigmentation and achieve
an even skin tone. As a consequence, these markets are looking
for increasingly efficient, fast-acting skin brighteners. At the same
time, these actives must be absolutely safe for cosmetic use.
Mechanism
Darker skin
A growing segment
Tanning
80
80%
60%
40%
20%
10%
0
1
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