SEPIWHITETM MSH

An innovative skin lightening molecule!

FLASH in vivo EFFICACY

(SEPPIC Patent )

C/3276/GB/01/march2006 / 1
 SEPIWHITE MSH
MAIN CAUSES OF PIGMENTATION DESORDERS ?

Solar
Ageing process
exposure

PIGMENTATION DESORDERS
Unesthetic aging spots
Uneven complexion

Hormonal disturbance :
-Contraceptive/ Estrogenic
treatment (due to menopausis) Irritation
/ Pregnancy Inflammation

C/3276/GB/01/march2006 / 2
 SEPIWHITE MSH
STRATEGY – SEPIWHITE MSH BIRTH

BIOLOGICAL DATAS

1. Stimulation of 2. « AGRP » proteins are

pigmentation by α MSH endogeneous antagonists of α MSH
(via a membrane receptor receptor (MC1R). The key position
« MC1R ») of « phenylalanine » controls this
binding

« AGRP » protein (key

α MSH position of Phenylalanine
on the binding site)

+ -
MC1R AGRP : Agouti Related Protein
MSH : Melanotropin

melanocytes
Melanin

⇒ Development of an α MSH antagonist = Lipoaminoacid

based on phenylalanine = SEPIWHITE MSH C/3276/GB/01/march2006 / 3
 SEPIWHITE MSH
STRUCTURE

Undecylenic acid (C11) Phenylalanine

(lipophilic) Essential aminoacid
(hydrophilic)

Undecylenoyl phenylalanine
CH2=CH-(CH2)8-CO-NH-CH-COOH
I
CH2-C6H5

Amphiphilic structure Pure, stable, colorless (white

=> Cutaneous bio affinity powder) and defined molecule

INCI name : Undecylenoyl phenylalanine

New molecule : ELINCS
Quasi drug Japanese file UNDERWAY
C/3276/GB/01/march2006 / 4
 SEPIWHITE MSH
LIGHTENING EFFICACY

1. A new mode of action on the α MSH cascade :

SEPIWHITE MSH
α MSH

+ -
MC1R Affinity for α-MSH receptor
ProtGαS

Adenylate Adenylate cyclase Inhibition

melanocytes
Cyclase

ATP cAMP cAMP Inhibition in melanocytes

Protein PKA Inhibition

Kinase A

Inactivated Activated Tyrosinase Inhibition / Maintains

Tyrosinase P-Tyrosinase the tyrosinase in a non active form

MELANOGENESIS

2. Skin lightening effect on skin in vitro model (melanocytes and

epidermis) and in vivo on volunteers. C/3276/GB/01/march2006 / 5
FLASH In vivo lightening efficacy
New Study performed in Asia

C/3276/GB/01/march2006 / 6
 SEPIWHITE MSH
FLASH LIGHTENING IN VIVO EFFICACY : ASIAN PANEL

1. Testing procedure : Tested formula 7034 :

A • SIMULSOL 165 (Glyceryl stearate and PEG-100 stearate - SEPPIC) 2.00 %
• MONTANOV 202TM (Arachidyl alcohol & behenyl alcohol & arachidyl glucoside 4.00 %
- SEPPIC)
• Cetylic alcohol 2.00 %
- Sepiwhite at 2% combined • Caprilic Capric triglyceride 7.00 %

with AHA & BHA – pH = 4 •

•
Ethyl hexyl methoxycinnamate ( Octinoxate)
Octyl Salicylate
7.00
5.00
%
%
(formula 7034) •
•
Butylmethoxy dibenzoyl methane ( Avobenzone)
Salicylic acid
1.50
2.00
%
%
• Talc 1.50 %
- 23 asian volunteers B • SEPIWHITE MSH (Undecylenoyl phenyl alanine – SEPPIC) 2.00 %
• Tromethamine 3.00 %
- 7 days of treatment on face •
•
Water / Aqua Qs 100 %
C SEPIPLUS 400 (Polyacrylate-13 & polyisobutene & polysorbate 20 – SEPPIC) 1.00 %
• SEPICIDE HB (Phenoxyethanol & Methylparaben & Ethylparaben& 0.50 %
- 2 applications per day Propylparaben & Butylparaben - SEPPIC)
• Xanthan gum 0.20 %

- Lightening chromametric D •
•
Water / Aqua
Chlorphenesin
10.00
0.10
%
%
measurement at D0 and D7 • Lactic acid 3.00 %
E • Fragrance 0.07 %
: Luminosity (L* Parameter)
and ITA (Individual Typologic
Angle) on normal skin and Test performed in Thaïland (Bangkok)
on pigmented spots
+ tolerance of the formula
(a* Parameter describing
erythema)

C/3276/GB/01/march2006 / 7
 SEPIWHITE MSH
LIGHTENING IN VIVO EFFICACY : ASIAN PANEL

1. Lightening effect after only 7 days of treatment => increase of

« luminosity » an ITA parameter in chromametry. (Formula 7034)

Increase of Luminosity Increase of ITA (depends on L* and b*)

Increase of ITA in Increase of ITA in

Increase of Luminosity 68% of volunteers 86% of volunteers
in 95% of volunteers
1,4 Increase of
Luminosity in
comparison to DO

* **
1,2
1,4
73% of volunteers
L* parameter
evolution in

**

in comp ar ison
1

ITA evolu tion

0,8
0,9

to DO
0,6
0,4
* 0,4
0,2
0
-0,1
D7 normal skin D7 pigmented spots
D7 normal skin D7 pigmented spots

ITA = Arc tan ((L*-50/b*)]x180/3,1415927

* : significant results ( p<0,05) in comparison to D0

** : highly significant results ( p<0,001) in comparison to D0
(L* and ITA value = average calculated on 100% of the tested volunteers )

After only 7 days of treatment, SEPIWHITE MSH significantly increases even

skin tone (ÊL* and Ê ITA). Complexion is brigthened, more radiant. The
pigmented spots tends to disappear. C/3276/GB/01/march2006 / 8
 SEPIWHITE MSH
LIGHTENING IN VIVO EFFICACY : ASIAN PANEL

2. Good tolerance of 2% Sepiwhite MSH formulated at pH 4 :

(Formula 7034)

Erythema decrease (a* value = average calculated on 100% of the

tested volunteers )

Decrease of Decrease of * : significant results ( p<0,05) in comparison

1,4
Erythema in 68% erythema in 82% to D0
comparison to DO

0,9 of volunteers of volunteers

a* parameter
evolution in

** : highly significant results ( p<0,001) in

0,4 comparison to D0

-0,1 * **
-0,6
D7 normal D7 pigmented
-1,1 skin spots

After 7 days of treatment, SEPIWHITE MSH significantly decreases skin

eythema (Ô a*). Sepiwhite MSH formulated at pH 4 and combined with AHA
& BHA is very well tolerated by the skin.

C/3276/GB/01/march2006 / 9
Summary of SEPIWHITE MSH
efficacy

C/3276/GB/01/march2006 / 10
 SEPIWHITE MSH
LIGHTENING EFFICACY - SUMMARY
Lightening effect at 2% on volunteers :
SEPIWHITE MSH
- « tan removal » test (28 days)
New concept for - Asian panel : visible effect after 2 months
an effective (formulated alone – pH 6,8) or very quick
lightener effect after 7 days (NEW study : Sepiwhite
MSH combined with AHA&BHA – pH 4)

Original mode of action: Quick Lightening effect on

reconstructed epidermis
α-MSH antagonist

Lightening effect on Melanocytes

(alone / with MSH / with UVB)

Only one acting by this pathway Better efficacy compared to

compared to classic whitening actives classic whitening actives
C/3276/GB/01/march2006 / 11
 SEPIWHITE MSH
STRONG POINTS

1. Undecylenoyl phenylalanine
ƒ Excellent cutaneous bio-affinity (lipoaminated structure)
ƒ Pure and unique patented molecule (ELINCS underway)

2. Original mode of action α-MSH Antagonist

3. Better efficacy compared to well known referenced molecules

(hydroquinone, arbutin, kojic acid, magnesium ascorbyl phosphate)

4. QUICK lightening effect proved in vivo on asian volunteers (7

days of treatment only)

5. Excellent tolerance when used at recommended level (2%)

6. Very good stability in any type of cosmetic formula (clear lotion

/ acid or basic white emulsions)

C/3276/GB/01/march2006 / 12
Formulation guidelines

C/3276/GB/01/march2006 / 13
 SEPIWHITE MSH
FORMULATION GUIDELINES
REMINDER :

Formulation’s advice of SEPIWHITE MSH at 2% :

1. Emulsions :
ƒ Fatty phase or aqueous phase incorporation at ≥ 60°C
ƒ pH < 5 => any type of formula
ƒ pH ≥ 6,8 => any type of formula
ƒ 5< pH ≥ 6,8 => addition of ethanol

2. Clear lotions :
ƒ Soluble in water if pH > 7

In all cases (for acid or basic formula) we advice to use a « weak base »
(such as Triethanolamine) for neutralizing SEPIWHITE MSH. The base
must be entirely incorporated at the beginning of the formulation.
C/3276/GB/01/march2006 / 14
 SEPIWHITE MSH
FORMULATION GUIDELINES

Perfect compatibility with classic whitening actives in

finished formula – Very stable trough time (color and odor)

AHAs, BHAs, kojic acid VCPMG

(=> PH <5) (=> pH >7)

Arbutin, hydroquinone,
plant extracts, ascorbyl
glucoside

Perfect compatibility in finished products with solar filters

C/3276/GB/01/march2006 / 15
 SEPIWHITE with AHA - BHA

Weak base
RECOMMENDATIONS
SEPIWHITE MSH

♦ Introduce the SEPIWHITE MSH

with the base into the water phase,
to control the good solubilization
(same as before) WATER PHASE
♦ Neutralization before Heat to 70-
emulsification (in excess in order to 85°C
neutralise also partially the AHA /
BHA)
♦ Use of weak base for Fatty
neutralization to avoid granular phase Homogenizing
texture over time wtih
BHA Water
♦ Avoid adding Sepiwhite and phase with
AHA/BHA in the same phase AHA
♦ Avoid to adjust the pH at the
end, possible to have granular
texture

C/3276/GB/01/march2006 / 16
 SEPIWHITE with AHA - BHA

LAST RECOMMENDATIONS

♦ Due to the formation of electrolytes by neutralisation

of the Sepiwhite MSH and AHA/BHA, choose a schema of
formulation resistant to electrolytes

♦ Best compatibility with lactic acid, citric and tartaric

acid, salicylic acid :
- with salicylic acid : up to 4%

- with AHA : up to 15%

•With glycolic acid : needs to adjust the process, longer stirring

•With gluconic acid : gives brownish emulsion

C/3276/GB/01/march2006 / 17
Nota

The analytical specifications warranted are only those mentioned on the certificate of analysis supplied with each delivery of the product.

Except as set forth above, SEPPIC* makes no warranties, whether express, implied or statutory, as to the product which is the subject of this document . Without limiting the
generality of the foregoing, SEPPIC* makes no warranty of merchantability of the product or of the fitness of the product for any particular purpose. Buyer assumes all risk and
liability resulting from the use or sale of the product, whether singly or in combination with other goods. The information set forth herein is furnished free of charge and is
based on technical data that SEPPIC* believes to be reliable. It is intended for use by persons having technical skill and at their own discretion and risk. Since conditions of use
are outside SEPPIC*'s control, SEPPIC* makes no warranties, express or implied, and assumes no liability in connection with any use of this information. Nothing herein is to be
taken as a license to operate under or a recommendation to infringe any patents.

* SEPPIC being: And, depending on the country:

SEPPIC S.A. SEPPIC UK Ltd SEPPIC ITALIA Srl

75, quai d’Orsay 50 Salisbury Road Via Quarenghi 27
75321 Paris cedex 07 PO Box 338 - Hounslow 20151 Milano
FRANCE TW4 6SH - ENGLAND ITALY
Tel. : +33 (0) 1 40 62 55 55 Tel. : +44 208 577 8800 Tel. : +39 02 38009110
Fax : +33 (0) 1 40 62 52 53 Fax : +44 208 570 2106 Fax : +39 02 38009140

GIVAUDAN LAVIROTTE S.A. SEPPIC Inc. SEPPIC China

56, rue Paul Cazeneuve 30, Two Bridges Road, suite 210 Room 510 Jin Tai Building
BP 8344 – 69008 Lyon Fairfield, New Jersey 07004-1530 58 South Mao Ming Road
FRANCE USA Shanghai 200020 CHINA
Tel. : +33 (0) 4 78 61 55 00 Tel. : +1 973 882 5597 Tel. : +86 (21) 64 66 01 49
Fax : +33(0) 4 72 05 60 89 Fax : +1 973 882 5178 Fax : +86 (21) 64 66 11 09

SEPPIC GmbH SEPPIC Belgium NV

ABC Tower Köln Nieuwe Weg 1
Ettore - Bugatti - Str.6-14 Haven 1053
51149 Köln-Porz B – 2070 Zwijndrecht
GERMANY BELGIUM
Tel. : +49 (0) 220 3890 3100 Tel. : +32 3 250 3911
Fax : +49 (0) 220 3890 3199 Fax : +32 3 250 3912

www.seppic.com

Subsidiary of the AIR LIQUIDE Group

C/3276/GB/01/march2006 / 18