ALISTIN ®

MULTI-POTENT ANTI-AGING COMPOUND

Anti-glycation
Anti-oxidation
Revitalization

MULTI-POTENT COSMETIC AGENT

Anti-wrinkle
Sun care
Sensitive skin
Body firming
SKIN CLINICAL DAMAGES INDUCED BY OXIDATIVE STRESS ALISTIN ®

Besides intrinsic aging, the skin is under the constant aggression of oxidative entities (solar radiations, pollution, physical
stress, etc.). The resulting oxidative stress can affect the structure of the cutaneous tissue and the metabolic activity
of its composing cells such as fibroblasts and keratinocytes. Since these factors are essential for the quality of the skin,
Exsymol developed Alistin, a peptidic compound which is able to protect the skin components such as the collagen
from these aggressions and to maintain the metabolic activities of the exposed cells.

Treatment with Alistin will both prevent and repair the daily aggressions-induced damages, allowing the skin to remain
healthy, firm and beautiful. Alistin acts in three different, non-exclusive, ways for a maximal efficiency:
1) Anti-oxidation / anti-stress
2) Anti-glycation
3) Metabolism stimulation

Hence, Alistin protects and/or reduces the noxious effects of an exposure to oxidative stress that can eventually lead
to severe damage as shown below:

Cellular level Skin level

Structural collapse, loss of elasticity, fine lines

1) Accumulation of oxidative forms
Protein alterations (including structural proteins) Tissue inflammation
DNA mutation
Less efficient dermis tightening activity
2) Protein glycation (including collagen) Homeostasis loss
3) Slackening of cell metabolism Dehydration

Exsymol’s solution : The decarboxy-carnosine

Carcinine (or Decarboxy Carnosine HCL), commercially available as Alistin, is a natural peptoid that has been
identified as a potent anti-glycant and anti-oxidant. Furthermore, it has the advantage of being relatively stable
when in contact with air. Derived from carnosine, another natural anti-oxidative compound, Carcinine displays
similar anti-oxidative properties while being substantially more stable than its parent compound as shown below.
This increased resistance to enzymatic degradation, makes Alistin a better candidate than carnosine for in vivo
and therefore cosmetic applications.

Furthermore, Alistin displays good bioavailability and localizes Alistin ( ) localizes on keratinocytes membrane as
assessed by immuno-histochemistry.
on the cell membrane (e.g. keratinocytes) as shown on human
reconstructed epidermis (HRE).

EXSYMOL - MONACO
 ALISTIN®

APPLICATIONS
• 2 HCl

INCI name: DECARBOXY CARNOSINE HCL

Carcinine is a nature-identical compound obtained from the decarboxylation of carnosine. Carcinine has
demonstrated its ability to protect the skin integrity from oxidative stress (by detoxification, scavenging and
damage repairing). Carcinine is commercially available as Alistin (10% aqueous solution) or Carcinine 2HCL
(powder).

SKIN BENEFITS
CELL DETOXIFICATION
Peroxidase-like activity (Babizhayev et al., 1994 - TI_0239)
Reduction of acid forms threatening the integrity of cells’ membrane
Faster DNA recovery after stress (Exsymol - DO_0751)
Global scavenger + free radical-induced damages repair (Exsymol, DO_1044)

SKIN STRUCTURAL PROTEINS (COLLAGEN) PROTECTION

Anti-glycation activity (Exsymol - DO_1133)
Combination of 3 defense mechanisms: competition, detoxification and reverse-glycation (Exsymol - DO_1133)

METABOLIC PROTECTION AND STIMULATION

Control of pro-inflammatory cytokine production (Exsymol - DO_1157)
Increase of sirtuin expression (Fréchet et al., 2010 - A3_1295)
Increase of collagen production rate (Fréchet et al., 2010 - A3_1295)

COSMETIC APPLICATIONS
ANTI-GLYCATION AND REVERSE-GLYCATION
ANTI-OXIDATION – Global protection
ANTI-WRINKLE – Deep wrinkles; Smoothness
SUN CARE – DNA protection; Photoaging
BODY FIRMING – Increase of collagen production; Contraction of the extra-cellular matrix
REVITALIZATION – On the cellular level; Sirtuin production
SENSITIVE SKIN – Soothing; Free radicals protection; Control of inflammation

EXSYMOL - MONACO
EXPERIMENTAL RESEARCH: IN VITRO ASSAYS ALISTIN ®

ALISTIN prevents and repairs cutaneous tissue damage.

Alistin for anti-glycation Alistin, a unique anti-oxidant
Alistin protects the collagen and other proteins from UV radiation can induce damage that can be monitored
the glycation processes at two different levels: by measuring the cells redox status. The skin can
1 Prevention: by glucose scavenging. slowly recover by itself from UV irradiation. However,
2 Reparation: by substituting itself to the collagen in a even after 24h, the self healing process still was not
transglycation process. complete. Treatment with Alistin led to a full recovery
in just about 8h.

re
re

pa
pa
Collagen Collagen Collagen
OH
Glycation process

ir
ir
H 2N N HN
+ 3
OHC Collagen
1 O
O Control
OH OH
HO
Reticulation
N OH
HO H
HO
UV Radiation

(GSH/GSSG)
Redox status
OH OH
HO Degradation 2
HO OH
HO HO
OH
UV + Alistin
2 HO

HO OH
HO

1
Alistin
Alistin OH
Collagen
N
Alistinn
WithAlisti

O Alistin
OH 0
Collagen protection 0h 1h 5h 8h 24h
HO
HO
N
With

H
OH
Elasticity and skin quality Time after UV irradiation
HO
HO OH

1 Prevention
HO

2 Reparation Alistin provides a fast and reliable protection against

oxidative stress-induced damage as measured above.
Hence, Alistin prevents the protein from cross-linking,
UV
while other anti-oxidants such as vitamin E fail at it.

re
pa
Alistin is even more potent than aminoguanidine,
Lipid peroxidation process

ir
OOH
a reference in anti-glycation. Furthermore, the final Nucleus
Cell
products of the reaction are neither toxic nor Cytoplasm death

mutagenic. Reticulated membrane

100 Alistin
Cross-linked proteins

75
(% of control)

OH
With Alistin

Cell
Nucleus
50 survival
Cytoplasm
25 Unaffected membrane

0 Control Alistin Vit E AminoGuanidine

Collagen +Glucosome (2mM) +Glucosome +Alistin

The skin preserves its structure and elasticity

Alistin reduces
the noxious LOOH
Time (min)

(lipid peroxide) into

Alistin protects from UV-induced DNA damage harmless alcohol
LOH, preventing the
UV radiations cause DNA mutations in epithelial cells. protein degradation
into toxic free
radicals as assessed
Time (min) by HPLC. This
anti-oxidative effect is unique and is not shared by
other anti-oxidants such as Vitamin E.
Alistin reduces UV-
induced mutations Alistin's anti-oxidative 300
MDA production (nM/min)

such as TT dimmers
( ) that might ultimately properties are also due
lead to the formation of
apoptotic cells such as sun- to its scavenging power 200

burn cells (
on HRE.
) as assessed as shown by its ability
to reduce MDA (a toxic 100

Alistin protects the DNA from UV-induced damage byproduct of oxidative

and mutation. Alistin stimulates the production stress) production.
0
Control Silymarin Carcinine
(10mM)
of DNA-protecting proteins, hence decreasing the
number of apoptotic cells. The skin is protected, healthier.

EXSYMOL - MONACO
 ALISTIN ®

EXPERIMENTAL RESEARCH: IN VITRO ASSAYS

ALISTIN has positive effects on skin cells’ metabolism and function.

Alistin reduces skin inflammation

125 125
IL-1α IL-8
Aggressions can lead to skin inflammation. Alistin, 100

(% of control)
100

IL-α release

(% of control)
IL-α release
when applied on human reconstituted epidermis,
75 75

50 50
reduces the secretion of pro-inflammatory cytokines 25 25

such as TNF-α, IL-1α and IL-8. 0 0

Hence, Alistin has anti-inflammatory and soothing 125

TNF-α
properties comparable to corticoids without the 100

TNF-α release
(% of control)
75
severe side effects. 50
UV irradiation
Hydrocortisone (0.1%)
Alistin (1%)
25

The skin is soothed. 0

Alistin energizes the skin Alistin stimulates collagen production

Sirtuins are proteins involved in aging, stress With age, the collagen production is reduced, the
resistance and cell metabolism through their ability firmness of the skin is reduced, wrinkles appear.
to maintain ATP levels. 200
Pro-collagen production

150
+66%
(ng/106 cells)

100 +20%

50

Control Carcinine (30mM) Carcinine (50mM)

0
Control Carcinine Carcinine
Alistin stimulates the production of sirtuins in a (20mM) (50mM)

dose dependant manner, hence enhancing skin cells Alistin stimulates fibroblastic collagen production
metabolic abilities. in a dose dependant manner. The skin is denser and
younger.

The skin is energized. The skin is denser.

Alistin increases skin firmness

Low serum (1%)
With age, fibroblasts’ firming abilities decrease. 50

Using collagen lattice, an in vitro model of dermis, 45

we measured the ability of primary fibroblasts to 40
Lattice diameter (mm)

contract the collagen fibers. Hence, for fibroblasts

35
in low serum media (1%), representative of an aged
dermis, the lattice contraction is much slower than
30
High serum (10%)

in a high serum media (10%) which is representative 25

of a young dermis. 20

Treatment of serum deprived fibroblasts with 15

Alistin accelerated the lattice contraction, showing 0

20 40 60 80 100 160
that Alistin has firming abilities.
Time (h)

The skin is firmer, younger.

EXSYMOL - MONACO
CLINICAL RESEARCH: IN VIVO TESTING ALISTIN ®

Realised under dermatological control, these in vivo assays

were performed on volunteering men and women.

Alistin reduces deep wrinkles

A 28 days treatment with Alistin visibly Lip to nose

wrinkles
reduced wrinkles. Of the 21 volunteers,
67% showed a visual improvement after the
treatment with Alistin.

Forehead
wrinkles
Average improvement (%)
showing improvement
Percent of volunteers

+72%
+250% D0 D28 D28
placebo Alistin
+29%

Softness Depth Softness Depth The skin is smoother, softer

Placebo Alistin(1%) and visibly youger.

Alistin as a booster for skin tone Alistin improves hair density

uniformity
Alistin enhances 0 100%
By increasing the
9%
Albatin (a melanogenesis 19% amount of hair
Melanin density (% of control)

9%
inhibitor) brightening -10
in the anagen
abilities. After 56 days phase, a 6 month
of treatment, volunteers 27%
Percent of volunteers

-20
treatment with
that received the Alistin, when
combined treatment 55%
coupled with
Albatin (1%)
displayed a 28% decrease -30
Capillisil HC,
36%
8
in melanin density and Albatin + Alistin(1%)
improves the hair
an increase in skin density for 80%
Skin luminosity increase (%)

luminosity of about 7%. of tested alopecic

All these values are higher 27%
4
18% men.
than the treatment with 0%
Alistin
Albatin alone. Hence, Control
2

(0.7%)+
by optimizing the effects Capillisil HC
0
of the skin brightener D0 D14 D28 D56 Very good improvement (>40%)

Albatin, Alistin Good improvement (20-40%)

contributes to the skin tone’s uniformity and to the Slight improvement (0-20%)

decrease in age spot number and intensity. Degradation (< 0%)

The skin is brighter, more uniform. The hair is denser, healthier.

EXSYMOL - MONACO
 ALISTIN ®

TECHNICAL CHARACTERISTICS
ANALYTICAL Decarboxy Carnosine HCL 10% (w/w)
Butylene glycol 8.18%
COMPOSITION Preservatives*
Water (sq) 100%

Limpid colorless liquid.

TECHNICAL pH ≈ 5
CHARACTERISTICS Density at 20°C≈ 1.0
Miscible with water, alcohol and glycols.
Non miscible with hexane, mineral and vegetal oils.

Different preservative systems are available in order to fit

PRESERVATIVES (*) with your requirements. Please contact us for additional
details about the available versions.

ALISTIN is perfectly tolerated.

TOLERANCE & TOXICITY Tolerance and toxicity studies were performed using both
STUDIES in vitro (cell culture and reconstructed epidermis) and in vivo
(human volunteers) methods.

Advised doses : 0.5 to 1.5%.

FORMULATION No particular formulation restriction.

ALISTIN is available in 1, 5, 30 and 60 kg drums.

AVAILABILITY ALISTIN is also available in powder (anhydrous)
as Carcinine 2HCL.

EXSYMOL - MONACO
 P8_1273GB1104B

EXSYMOL S.A.M. - 4 avenue Albert II - MC 98000 MONACO

Tel. : +377 92 05 66 77 - Fax : +377 92 05 25 02
E-mail : exsymol@exsymol.com - Internet : http://www.exsymol.com