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A CUTTING-EDGE MOLECULE FOR A

RADIANT SKIN TONE

v5
THE CULTURE OF A BRIGHTER SKIN (I)

Skin brighteners use and consumers


consumers’ demand is growing worldwide.
worldwide

• In Western countries, skin brighteners are applied for the


prevention and treatment of irregular hyperpigmentation, resulting
in an evener skin tone.

• In Asia, brighter skin is a symbol of beauty and femeninity. The use


of skin brightening agents is widely extended by traditional beliefs.
o The need of whitening the skin is so high that most of anti-aging
products contain also whitening ingredients and UV filters.
THE CULTURE OF A BRIGHTER SKIN (II)

Japan
China Sales of Whitening
30% of people use Skin products
d t are 1515-17%
17% off
Whitening products Skin Care sales

Thailand
Even more population
(60%) uses Skin
Whitening products
THE CULTURE OF A BRIGHTER SKIN (III)

Whitening and brightening


products
d t accountt ffor 60% off
new products among the top
Anti-age spots ethic beauty launches
(Mintel GNPD Beauty Innovation)

Even skin tone


GROWTH IN SKIN LIGHTENING BY MARKET

(US $ Million)
Milli )

AC Nielsen, 2007
SKIN COLOUR

The colour of the skin and hair depends on the


amount, distribution and type of melanin.

• Melanins are pigmented biopolymers synthesised in


melanocytes in the DEJ (Dermo-Epidermal Junction).
• Melanosomes with melanins migrate and they are
transferred to keratinocytes in skin.

melanins melanins SKIN COLOUR

MELANOCYTES KERATINOCYTES
CHANGES IN SKIN PIGMENTATION

• Typical pigmentary changes appear


during intrinsic aging and photoaging:

HYPERPIGMENTATION
melasma, freckles, age spots and senil lentigines

abnormal accumulation acute or persistent


of melanin UV exposure
THE SEARCH FOR A NEW SKIN BRIGHTENER

• Inhibition of melanin synthesis by inhibition of tyrosinase activity.


• Tyrosinase: key enzyme of melanogenesis.

melanins SKIN COLOUR

MELANOCYTES

Need for novel skin brightening agents with increased


efficacy
ff y and improved
p safety
f yp profiles
THE IDEAL SKIN BRIGHTENER

According to Dooley1, new depigmentation products should include the


following desirable features:

PROPERTIES
Inhibition of mammalian tyrosinase 9 (human tyrosinase)
Lack of toxicologic or mutagenic potential 9 (impeccable safety profile)
Clinical efficacy 9 (proven in vivo)
Formulation stability 9 (high stability)
Novelty and patent protection 9

PHOTOPROTECTIVE EFFECT
prevention of UV-induced skin damage

1DooleyTP. Topical skin depigmentation agents: current products and discovery of


novel inhibitors of melanogenesis. J Dermatolog Treat. 8:275-279, 1997.
CHROMABRIGHT® STABILITY

INGREDIENT %
Tested in an O/W emulsion
Water qsp 100
Mineral Oil (Paraffinum Liquidum) 10
Polyacrylamide, C13-14 Isoparaffin, Laureth-7 3
CHROMABRIGHT® 0.05

120 0,06

100 0,05
ncentration (%)

Conccentration (% )
80 0,04

60 0,03
Con

40 0,02

20 0,01

0 0
0 months 1 month 2 months 3 months 4 months 6 months 3,8 5,0 8,4
Time pH
Room temp. 40 ºC
room temp 60 ºC

Chromabright® proved to remain stable after


6 months and at different pH final formulations
CHROMABRIGHT® SAFETY

Completely safe profile:

o Ocular irritation (HET-CAM test).


o Phototoxicity.
Phototoxicity
o Cytotoxicity on human epidermal keratinocytes.
o Cytotoxicity on 3T3 fibroblasts.
o Bacterial reverse mutation test (Ames test).
o Cytotoxicity on human primary melanocytes.
o Skin sensitisation.

Chromabright® showed no signs of toxicity in any of the tests above


CHROMABRIGHT® EFFICACY

IN VITRO
o Inhibition of mushroom tyrosinase activity.
9 It is the most used assay to assess potential depigmenting agents.

o Inhibition of endogenous human tyrosinase activity.


9 This assay should be considered much better than mushroom tyrosinase.

o Depigmenting effect on human melanocytes.


o Melanogenesis inhibition on human epidermal melanocytes.
o Photoprotective effect on human epidermal keratinocytes.

IN VIVO
o Skin brightening effect on human volunteers.
IN VITRO EFFICACY (I)

1. Tyrosinase inhibition • L-Dopa (tyrosinase substrate) was digested in the


presence of 1mM Chromabright® and the enzyme.
• Absorbance variations were measured at 475 nm.
• Kojic acid 0.1mM was used as positive control.
Mushroom tyrosinase

dopachrome production
120 -20
on
% dopachrrome productio

100 0

% inhibition of
20
80
37.0% 40
60 55.5% 37% inhibition of mushroom
60
40
80 tyrosinase activity

o
20 100
0 120
Control Kojic acid CHROMABRIGHT®
(0.1mM) (1mM)

Endogenous human tyrosinase


120 -20 dopa
% dopachrome producttion

achrome produ
100 0 % inhibition of
20
80
43.0% 40
43% inhibition of endogenous
60
69.0% 60 human tyrosinase activity
40
80
o
uction

20 100
0 120
Control Kojic acid CHROMABRIGHT®
(0.1mM) (1mM)
IN VITRO EFFICACY (II)

2. Depigmenting effect on human melanocytes cultures

% Lightening efficacy • Incubation of plated human melanocytes for 5 days.


• Daily addition of fresh medium containing 0.1mM
45 9%
45.9% Chromabright® or Kojic Acid.
Acid
50% • Kojic acid 0.1mM was used as positive control.

40% 30.2% • The lightening efficacy was assigned by counting the


cells showing melanin staining and the total number of
30% cells.
ll

20%

10%

0%
Chromabright® exhibits a better
Kojic acid CHROMABRIGHT®
(0.1mM) (0.1mM) depigmenting effect than Kojic Acid
on human melanocytes
IN VITRO EFFICACY (III)

3. Melanogenesis inhibition on human melanocytes cultures (I)

• Primary human melanocytes (HEMn-DP) cells were seeded and


allowed to grow for 2 weeks.
120 • Melanocytes were treated on days 1, 3, 6, 8, 10, 13, 15 and 17 with:
100 o Chromabright® (5µM, 10µM, 100µM, 150µM and 200µM)
anin (pg/cell)

80 o Hydroquinone (10µM)

60 o MAP (Magnesium Ascorbyl Phosphate) (10µM)


% of mela

40
o Kojic Acid (10µM)
o Arbutin (10µM)
20
• Control: medium without treatment.
0
• After 20 days of culture, melanin concentration was determined by
measurement of absorbance at 450nm and values were normalised
respect to the number of cells per well.

Chromabright® inhibited melanogenesis at all tested


concentrations in a dose-dependent manner
concentrations,
IN VITRO EFFICACY (IV)

3. Melanogenesis inhibition on human melanocytes cultures (II)


By optical microscopy

Control 200µM

10µM Hydroquinone 10µM Chromabright® melanogenesis


inhibition efficacy was higher than
Similar activity at the same Arbutin, Kojic Acid and MAP
concentration, but Chromabright®
did nott presentt cytotoxicity
t t i it at the same concentration (10µM).
(10µM)

while Hydroquinone cytotoxic effect was


clearly observed, at the dosages tested.
IN VITRO EFFICACY (V)

4. Cellular photoprotection • Test based on the determination of the protective effect of


a chemical when tested in the presence of a cytotoxic dose
of simulated solar light.
• Irradiation to cells implies a decreased uptake of the vital
dye Neutral Red (NR).

NRU photoprotection test in Human Epidermal Keratinocytes

190% increase in cell viability

Chromabright® helps to prevent the


skin-damaging effects of UV radiation.
IN VIVO EFFICACY (I)

1. Brightening effect • Measurements were taken before application, after 30 and 60 days
of treatment.
o 20 Asian female volunteers, aged 18 to 46. • Parameters used to evaluate the effects:

o A cream containing 0.1% Chromabright® was • L* (Luminance): represents the relative brightness from
total darkness (L*=0) to absolute white (L*=100)
applied on one side of the face twice daily and
a placebo cream on the other side for 60 days. • ITAº (Individual
(I di id l Typologycal
T l l Angle):
A l ) categorises
t i skin
ki colour,
l
obtained combining L* and b* (yellow-blue colour axis)
o Evaluation: means of a Chromameter CR-300.

A cream containing 0.1% Chromabright®


induced a significant brightening effect
after 30 and 60 days
IN VIVO EFFICACY (II)

• % clinical improvement:
2. Depigmenting effect o Score 0: 0%
o 10 volunteers, aged 18 to 70, with melasma and/or actinic o Score 1: 1-25%
lentigines applied a cream containing 0.5% Chromabright® on o Score 2: 26-50%
their face and/or hands twice a day for 60 days. o Score 3: 51-75%
o Cli i l and
Clinical d iiconographic
hi controls
t l were performed
f d att th
the S
o Score 4 76-100%
4: 76 100%
beginning of the study, and after 30 and 60 days of application.

3 50
3.50 3.40
3.11
3.00
2.50 2.20 2.11
2.00
ore

T30
0 days 30 days
Sco

1.50 T60
1.00
0.50
0.00
MELASMA LENTIGINES

80% of the volunteers with melasma and 0 days


y 60 days
y
77.8% with lentigines experienced a
significant improvement after 60 days
COSMETIC BENEFITS

Safety & efficacy


together

Pure molecule High efficacy Photoaging Safety


in short time prevention
p

High stability Completely safe


and keeps o Significant brightening Cellular toxicological
purity of 100% effect in only 2 months photoprotection profile
demonstrated
o High depigmenting power
after 30 days
TECHNICAL INFORMATION

DESCRIPTION
A new patented ingredient designed for skin brightening applications that
shows neither cytotoxic effects, nor any irritation or sensitisation reaction.

APPEARANCE
Powder.

INCI
Dimethylmethoxy Chromanyl Palmitate.

PROPERTIES
It induces a significant lightening effect on the skin, at the same time that
fights against photoaging.

APPLICATIONS
Chromabright® can be incorporated in cosmetic formulations containing oil
or silicon phases where a brightening effect on the skin is desired.

DOSAGE
0.1-0.5%
A CUTTING-EDGE MOLECULE FOR A
RADIANT SKIN TONE

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While the claims and supporting data provided in this publication are believed to be reliable and they are
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warranties are disclaimed.
disclaimed The recipient is solely responsible for ensuring that products marketed to belong
g to their respective
p and lawful owners
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industrial and intellectual property rights identified herein. Recipient of this publication agrees to
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arising from recipient’s use of any claims or information in this publication, including, but not limited to,
use in advertising and finished product label claims, and not present this publication as evidence of finished
product claim substantiation to any regulatory authority.

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