EX

SY
M
ALBATIN OL

Hydroglycolic solution (water : butanediol-1,3) containing 22.5% of 1-aminoethylphosphinic acid

INCI Denomination : AMINOETHYLPHOSPHINIC ACID (and) BUTYLENE GLYCOL
(and) WATER

Chemical definition
ALBATIN is a solution of 1-aminoethylphosphinic acid, or Ala-P
(phosphinic analogue of alanine),
melanogenesis inhibitor, stable in aqueous solution.

O
H
H3 C P
-
O

NH3+

Analytical composition Technical characteristics

1-Aminoethylphosphinic acid 22.50 g Liquid : limpid, colorless to slightly yellow
Butanediol-1,3 7.70 g pH : around 4
Sodium methyl parahydroxybenzoate 0.15 g Density at 20 C : around 1.1
Citric acid monohydrate 0.20 g Miscible with water, glycols and alcohol.
Water sq 100.00 g Not miscible with hexane, mineral and vegetable oils.

Availability
1, 5 or 30 kg drums

Cosmetic uses

Skin lightening products

Anti age-spots products

ALBATIN can be formulated alone or in association,

in day care products,

anti age spots creams

and skin lightening products.

 BIOLOGICAL ACTIVITIES - A NON-TYROSINASE INHIBITOR ACTIVE FOR SKIN LIGHTENING
A LBATI N
IN VITRO ACTIVITY :
MELANOGENESIS INHIBITION ON CULTURE OF S91 MELANOCYTES
MECHANISM OF ACTION OF ALBATIN

- ALBATIN is a stable solution of Ala-P (Graph 4).

- ALBATIN is not cytotoxic.
- ALBATIN is not an inhibitor of the enz ymatic activity 100

The inhibition potential of ALBATIN is evidenced by quantification of the of tyrosinase.

melanin formed after UV irradiation (30 mJ/cm2 and 285 nm) of cultures of S91 As for its
mechanism,
- ALBATIN is involved in other steps of melanogenesis. 90
melanocytes, which are further incubated (16 hours) with the actives to be ALBATIN opposes the

% of polymerisation
tested. B y stabilizing DOPAchrome (Graph 2) and inhibiting 80
oxidative polymerization of
the enzymatic activity of the DOPAchrome DOPAchrome, since a dose-
tautomerase (Graph 3), ALBATIN opposes further 70
dependent inhibition of the
spontaneous polymerization and thus limits the formation of polymers (melanin)
14 formation of melanin (Graph 1). is observed when ALBATIN is
Melanin mg/g of protein

60
12 used (Graphe 2).
- ALBATIN maximizes the melanogenesis inhibiting
10 50
A LA -P O properties of other skin lighteners (e.g. Arbutin). 0 2,5 5 7,5 10 12,5 15 1
8 H Graph 2 [ALBATIN] in eq. ALA-P
6 H3C P -
O
4
+
2
NH 3
Reference Irradiated Kojic acid Ascorbic acid ALBATIN
melanocytes melanocytes 3.3 mM 0.33 mM (0.5 mM Ala-P)

DCT activity (mU/mg of protein)

Graph 1 HO CO2H O CO2H
A decrease of the 16
CO2H
Tyrosinase Tyrosinase enzymatic activity of DCT
NH 2 NH 2 NH 2 ( D O PA c h r o m e 14

St
HO HO O
Graph 1 (here above) shows that the melanogenesis inhibition potential of tautomerase), measured

ab
DOPA DOPAquinone

ili
ALBATIN is as efficient as that of kojic acid and ascorbic acid at doses Tyrosine on cultures of S91 12

sa
commonly used for in vitro tests. Glutathione melanocytes, has been

tio
or 10

n
evidenced when the cells
HO Cysteine
were treated with 8
CO2H HO CO2H ALBATIN (Graph 3). Reference Reference Reference + U.V
HO NH + UV + ALBATIN (1 mM Ala-P)
NH 2 Graph 3
Effect of ALBATIN HO
S
in vitro CysteinylDOPA This inhibition of the enzymatic activity of DCT may be
O
HO Spontaneous explained by a stabilization of Dopachrome.
CO2H H2N CO2H
n+
HO NH M HO NH
STABILITY
DHI DOPAchrome
Tyrosinase DOPAchrome
and/or tautomerase
HO CO2H
Peroxidase TRP-2
HO 100%
O NH 2 ALBATIN
CO2H N
80%
HO NH S Alanyl-hydroxy- Ascorbic acid
reference cells reference cells + UV reference cells + UV O NH 60%
+ ALBATIN (1 mM Ala-P) DHICA benzothiazine +
Sodium bisulfite
Indole-5, 6-quinone oxidase 40%

Figure 2 : The pictures show the efficacy of ALBATIN on cultures of DOPA TRP-1
20%
positive S91 melanocytes submitted to UV irradiation (3 x 50 mJ/cm2). O Ascorbic acid
0%
CO2H Days
0 10 20 30
Eu-Melanins O NH Pheo-Melanins
Graph 4
Indole-5, 6-hydroquinone-
2-carboxylic acid The graph shows a very good stability of ALBATIN in aqueous solution
Figure 1 : Biosynthesis of melanine in melanocytes. compared to that of ascorbic acid, over a period of 1 month (Graph 4).
 Tolerance study
The tests performed in vitro and in vivo show that the product is not irritant :
1. In vitro (alternative methods) :
- ocular irritation (on fibroblasts culture isolated from rabbit cornea)
- cutaneous irritation (on reconstituted epidermis)
- genotoxicity
- phototoxicity
2. In vivo
- photo-sensitization, irritation and sensitization on healthy human volunteers

Formulation
ALBATIN is a hydroglycolic solution, stable at pH between 3 and 9. It is recommended to use
between 0.5 and 1.5% when ALBATIN is used as sole melanogenesis inhibitor.
Its activity would be optimized should ALBATIN be associated with other melanogenesis inhibitors
such as ascorbic acid and derivatives, kojic acid, arbutin,
ALBATIN can be formulated without restriction into the aqueous phase of a gel, of an emulsion or
a solution.

Studies
(available on request)

Technical data
*
Melanogenesis study on cultured S91 melanocytes
*
Effect of ALA-P on Dopachrome
*
Interest of associating ALBATIN with arbutine or kojic acid to improve the
inhibition of melanogenesis
*
Evidence of lightening activity of ALBATIN on tanned reconstituted epidermis
*
Ocular irritation, cutaneous irritation (alternative methods), genotoxicity,
phototoxicity, sensitization on human volunteers.

EXSYMOL S.A.M. - 4 avenue du Prince Hrditaire Albert - MC 98000 MONACO

Tel. : +377 92 05 66 77 - Fax : +377 92 05 25 02
A3_0124GB0205D.pdf

E-mail : exsymol@exsymol.com - Internet : http://www.exsymol.com