L(+) Lactates for Skin Whitening
Content of the presentation
Content L(+) Lactates for Skin Whitening
1. Mechanism of skin-whitening
2. Whitening the start
3. In vitro data
4. In vivo data Vitamin C + Lactates
5. More whitening research
6. Costs / Concentrations
7. pH effect / AHA
8. Conclusions
9. Discussion
1. Mechanism of skin-whitening
Mechanisms of whitening
A
CH2
COOH
CH
Tyrosinase formation-suppressive
(Lactates)
Tyrosinase
N H2
HO
se
ida )
x
-o ase
pa
Do rosin
(Ty
B
CH2
COOH
CH
N H2
CH2
CH
Dopaquinone
COOH
NH2
HO
Tyrosine
Inhibition
Tyrosinase activity
HO
3,4-Dihydroxy-phenylalanine
(Dopa)
HO
HO
COOH
N
H
Leucodopachrome
HO
COOH
N
H
Dopachrome
O
O
HO
N
H
5,6-Dihydroxyindole
O
N
H
Indole-5,6-Quinone
N
H
Melanin
Reduction
of Melanin
1. Mechanism of skin-whitening
Types of whitening action
Denaturation and death of pigment cells (C)
Tyrosinase inhibiting action (B)
Suppressing the formation of Tyrosinase (A)
1. Mechanism of skin-whitening
Whitening ingredients overview
Tyrosinase
suppressive
action (A)
Tyrosinase
inhibiting
action (B)
Ascorbic acid (Vit-C) derivatives
Kojic Acid
Arbutin
Licorice
Nicotinamide (Vitamin B3)
Mulberry extract
Vegetable/Herb extracts
Lactates
Hydroquinone
Reduction
of melanin
(C)
2. Whitening the start
Whitening of lactates the start
Tyrosinase inhibitory/suppressive action of organic acids
(in vitro) ( + = activity, = no activity)
Organic acids/salts
Tyrosinase Melanogenenis
inhibitory
suppressive
activity
activity
Tyrosinase
formation
suppressive
activity
Lactic acid/Sodium Lactate
Asparaginic acid
Glutaminic acid
Citric acid
Fumaric acid
Malic acid
Ascorbic acid (Vit. C)
European patent application 0423 929 A1.
2. Whitening the start
Whitening of lactates the start
L (+) Lactic acid and lactates in vivo whitening experiment
Percentage of test-objects with significant whitening results
Lactate concentration (w%)
2%
5%
8%
20%
Sodium Lactate
35%
80%
95%
100%
Ammonium Lactate
35%
75%
100%
Magnesium Lactate
30%
75%
90%
100%
Conditions: 20 test-subjects
pH=5.5
measurement after 24 days
applying cream 3 times daily
European patent application 0423 929 A1.
3. In vitro data
In Vitro Data Melanoderm
Objective:
To assess effect of whitening agents on tyrosinase
suppression/inhibition (in vitro measurement; Melanoderm)
Conditions:
Whitening ingredients tested: Lactic acid(3%), Kojic acid(1%),
Ascorbic acid (1%) and MAP (1%)
Melanoderm: in vitro model of human epidermis. Model can
be used to evaluate efficacy, stability and toxicity of whitening
agents.
Journal of Cosmetic Science. Nov/Dec 98. Vol 49, p.361-367
3. In vitro data
In Vitro Data Melanoderm
Effect of whitening agents on tyrosinase inhibition/suppression
50
40
30
20
10
0
Lactic
acid
(3%)
Kojic
acid
(1%)
MAP Ascorbic
(1%)
acid
(1%)
Ascorbic acid only reveals modest results (oxidation?)
Lactic acid and kojic acid reduce resp. 46% and 48%
Journal of Cosmetic Science. Nov/Dec 98. Vol 49, p.361-367
4. In vivo data Vitamin C + Lactates
In vivo research Vitamin C + Lactates
Objective:
To determine whether L(+) Lactic acid by itself or supplemented
with ascorbic acid can whiten the skin
To asses if synergistic effects between A and B type whitening
ingredients could possibly take place.
Conditions:
70 test subjects, Caucasian females ages 25-70
(rated 3 or 4 via Fitzpatrick Scale)
3 formulations, applying twice a day
Objective (Minolta Chroma meter) and subjective (clinical
grading; 1-100 scale) whitening measurement
Duration whitening test 12 weeks (t=0, 4, 8, 12 weeks)
Smith, International Journal of Cosmetic Science 21: 33-40 (1999)
4. In vivo data Vitamin C + Lactates
Methodology Test subjects
Caucasian skin type 3 to 4 on Fitzpatrick scale
Fitzpatrick scale
Skin type: Sun burning and Tanning
1. Always burns easily; never tans
2. Always burns easily; tans minimally
3. Burns moderately; tans gradually
4. Burns minimally; always tans well
5. Rarely burns; tans profusely
6. Never burns; deeply pigmented.
Smith, International Journal of Cosmetic Science 21: 33-40 (1999)
4. In vivo data Vitamin C + Lactates
Formulations
1.) Vitamin C (1%)
2.) Lactic acid (8.8%)
3.) Vitamin C (1%) + Lactic acid (8.8%)
Conditions:
pH 5, mild formulations, but not stable
New formulations freshly prepared every 2 weeks
3 formulations, applying twice a day
Smith, International Journal of Cosmetic Science 21: 33-40 (1999)
4. In vivo data Vitamin C + Lactates
Measurement by Clinical grading
Vitamin C +
Lactic acid
80
75
Lactic acid
70
65
Vitamin C
s
th
s
on
th
3
on
m
2
on
th
60
Vitamin C + Lactic acid significant whitening after 3 months
Smith, International Journal of Cosmetic Science 21: 33-40 (1999)
4. In vivo data Vitamin C + Lactates
Measurement by Clinical grading
14
12
10
8
6
4
2
0
Vit C (1%)
Lactic acid (8.8%)
Vit C (1%) +
Lactic acid (8.8%)
Months
Synergistic whitening effects achieved when Vitamin C is
combined with Lactates in one formulation
Smith, International Journal of Cosmetic Science 21: 33-40 (1999)
5. More Clinical Research
More Clinical Research
Objective:
To assess and compare the performance/ effectiveness of
frequently used whitening ingredients in vivo.
Conditions:
Vehicle controlled double blind not randomized clinical trial
7 formulations, applying twice a day
30 test subjects; female, Asian skin type, 18-45 yr. old
Objective (Mexameter) and subjective (4 point scale)
whitening measurement
Duration whitening test 12 weeks (t=0, 4, 6, 8, 12 weeks)
Philippine Dermatological Research and Testing foundation
5. More Clinical Research
Formulations
Products
Concentration
Control/Placebo
0%
Sodium Lactate 60%
15%
Arbutin
1%
Licorice
0.3%
Kojic acid
1%
Sodium Lactate 60% + Arbutin
15% + 1%
Sodium Lactate 60% + Licorice
15% + 0.3%
Sodium Lactate 60% + Kojic
15% + 1%
G
H
K2 Glycyrrhizinate = licorice
Mild, stable and commercial formulations; pH=5
All formulations equal except for whitening ingredient
F,G, H included to asses possible synergistic effects
Philippine Dermatological Research and Testing foundation
5. More Clinical Research
Methodology
Objective measurement
Mexameter (M16), Courage and Khasaka, Germany
(Melanin Index)
Scale 400-700, dark-skins range 450-550
Duration whitening test 12 weeks (t=0, 4, 6, 8, 12 weeks)
Photo-types and ranges Mexameter
I:
II:
III:
IV:
V:
VI:
Celtic type (very fair skin, red hairs, freckles) 400-470
Caucasian white (fair skin, blond, blue eyes): 410-490
Mixed type (blond-brown hair, brown eyes): 420-510
Mediterranean type (dark hair, brown eyes): 420-520
Dark skin: 450-550
Black Skin: 520-700
Philippine Dermatological Research and Testing foundation
5. More Clinical Research
Methodology
Subjective Measurement
On a 4-point scale.
Assessment by dermatologist and panelist themselves
Subjective measurements predominantly used:
Clinical grading: using color cards, comparison with skin
color; expensive, 0-100 point scale, trained staff needed
but very reliable
4-point scales: scaling of skin-color on 4 point scale,
cheap, to be used in combination with objective
measurement.
Philippine Dermatological Research and Testing foundation
5. More Clinical Research
Objective measurement
Whitening effect in time (3 months)
Mexameter-values
550
Control/Placebo
545
Sodium Lactate 15%
Arbutin 1%
Licorice 0.3%
540
Kojic acid 1%
SL + Arbutin
SL + Licorice
535
SL + Kojic
530
T=0
4 weeks
6 weeks
8 weeks
12 weeks
Significant whitening effect for all treatments after 6 weeks
C&T Jan 2001, whitening effect of frequently used whitening ingredients
5. More Clinical Research
Objective measurement; T=0 is index 100
Whitening effect in time (3 months)
100.5
Control/Placebo
100
Sodium Lactate 15%
99.5
Arbutin 1%
99
Licorice 0.3%
98.5
Kojic acid 1%
SL 15% + Arbutin 1%
98
SL 15% + Licorice 0.3%
97.5
SL 15% + Kojic 1%
97
1
Form. without Sodium Lactate show stabilizing after week 6
C&T Jan 2001, whitening effect of frequently used whitening ingredients
5. More Clinical Research
Objective measurement
mean mexameter differences (versus T=0)
Differences in mexameter readings between T=0 and wk 8 resp. 12
16
14
12
10
8
6
4
2
0
Control/Placebo
Sodium Lactate 15%
Arbutin 1%
Licorice 0.3%
Kojic acid 1%
SL+Arbutin
SL+Licorice
SL+Kojic
Week 8
Week 12
5 points difference on mexameter scales is significant
Sodium Lactate, SL+Kojic and SL+Licorice best performing
C&T Jan 2001, whitening effect of frequently used whitening ingredients
6. Costs / Concentrations
Cost comparison formulations
Products
Sodium Lactate 60%
Price
4 US$/kg
Arbutin
750 US$/kg
Licorice
325 US$/kg
Kojic acid
400 US$/kg
10
Control/Placebo
Sodium Lactate 15%
Arbutin 1%
Licorice 0.3%
Kojic acid 1%
SL + Arbutin
SL + Licorice
Costs in formulation (USD/kg formulation)
SL + Kojic
Sodium Lactate cheapest and most effective whitening ingredient
C&T Jan 2001, whitening effect of frequently used whitening ingredients
6. Costs / Concentrations
6. Summary on concentrations needed
Whitening effect is related to the lactate ion
Nr
Product
Product 100%
Lactate
ion
8.8% Lactic acid 90%
8% Lactic acid (100%)
7.9%
15% Sodium Lactate 60%
9% Sodium lactate (100%)
7.2%
Correction for concentration
Correction for Mw (H=1; Na=23; L=98)
Conclusion: At least 7% Lactate ion should be added
Equivalent to:
15% Sodium Lactate 60%
(= 7.2% Lactate)
8% Lactic acid 90%
(= 7.1% Lactate)
12% Calcium Lactate
(= 7.0% Lactate)
Calcium lactate: Mw=308 g/mole, 5H20 =90 g/mole, Ca2+= 40 g/mole, Lactate = 178 g/mole
7. pH-effect / AHA
Lactates and pH
Experiments carried out at relatively neutral pH (5)
At pH 5, hardly any Lactic acid is available in final formulation
8
pH
pH=5 in formula:
100 Sodium Lactate
6 Lactic acid
4
3
2
0
% Lactic acid / %Sodium lactate
10
7. pH-effect / AHA
pH-effect / AHA
Rejuvenating benefits of Lactates; improvement in % after 8 weeks treatment
60
50
Skin cell renewal
increase
40
Increase in skin
firmness
% 30
20
Reduction of
lines and
wrinkles
10
0
pH=7
pH=3
Exfoliating effect of Lactates increases at lower pH levels
Exfoliating effect Lactates could enhance pace of whitening
8. Conclusions
Conclusions L (+) Lactates in whitening
L(+) Lactates are safe and effective and low
cost whitening ingredients
Formulated at lower pH incorporates additional
peeling/exfoliating properties
Additional moisturizing properties added to
the whitening formulation
Possibility to add properties such as ceramide
increase and mineral enrichment
9. Discussion
Intended Future Clinical Research
Determine whitening capability/performance
of Lactate salts (Zn-L, Ca-L vs. Na-L)
Study the synergistic effects (if any) with
other popular whitening active ingredients
like Nicotin amide, Ascorbic acid, vegetable
extracts like Brassica rapa juice extract
9. Discussion
Safety concerns Hydroquinone / Kojic acid
Hydroquinone is suspected to be carcinogenic
FDA ruling due for 30 December 2006 on
imposing a ban on Hydroquinone
Japanese dermatologists suspect Kojic acid
may be carcinogenic (?)
Japanese and Korean government ordered to
stop using Kojic acid until investigations end
Switzerland has banned Kojic acid
