Chemical family - Biosil Technologies Inc

PRO-D.S.B. EXSYMOL

Pro dimethylsilanediol salicylate
(an oil solution dosed at 10 %)
INCI denomination : DIMETHYL OXOBENZO DIOXASILANE / ETHYLHEXYL PALMITATE
MHW database n° : 21200CZY00064000

Chemical family

Pro-D.S.B. is a silicon organic derivative, chemically pure, oil monomer to formulate under certain imperative
conditions : without water or alcohol. With a gentle hydrolysis at the time of the application on the skin or the
mucous, it will form a biologically active SILANOL, very rich in hydroxyl functions. It possesses the biological
properties peculiar to SILANOLS integrating an answer given by the salicylate radical presence.

Analytical composition Technical characteristics

Salicylate dimethysilyl 100.0 g limpid liquid, slightly opalescent with yellow
14.5 g shades
of which silicon refraction index 1.45
1000.0 g density at 25°C about 0.850
octyl palmitate qs oil miscible
incompatibilities : water, alcohol, glycol
(quick hydrolysis)

Availability

drums of 1, 5, 30 liters

Uses

Soothing and anti-inflammatory care products

(products for skins with acnea problems, sensitive skins, sun and after-sun products,
after-shave, post depilatory, peeling in order to restore the functional pH of the skin...)

*

Body and face moisturizers

(moisturizer action due to SILANOL structure potentialized by a sensation
of soothing activity)
*

Anti-ageing : prevention

(antioxidant and restructuring activity due to the SILANOL structure)
*

Colour cosmetics and treatments : mascara and lipsticks

(in small quantities 0.5 to 2‰ for restructuration and protection
against oxidative phenomena)
*

Hair products and nail treatment

With a silicon content of about 0.5‰, it allows to stimulate hair and nail metabolism.
We observe a stop of the hair loss, a modification of the nails fragility
and in both cases a growth acceleration.

BIOLOGICAL

Mecanism, action and Pro-Drug interest

PRO-D.S.B. is the D.S.B. C precursor

O PRO-D.S.B.
Oil Monomer
O
Si Me Chemically
O Me Pure

Experiment demonstrates IN COSMETIC, whatever the
formulations, they should not
that by a controlled contain any water or alcohol.

and gentle hydrolysis

an hydrosoluble oligomer

is formed (Hydrogen bonds)

SALICYLATE A gentle hydrolysis occurs
at the cutaneous tissues level,
DIMETHYLSILANOL Me Me
with in situ formation of
Me Me Me SALICYLATE DIMETHYLSILANOL
O OH
O Si Si Si biologically active
HO O O
The skin thus creates an active SILANOL at its rhythm
Me
Diffusion study
OH

OH OH

OH

HYDROLYSIS ON SYNTHETIC MEMBRANE HYDROLYSIS ON EPIDERMIC TISSUES

Cross section of a diffusion chamber • Reconstituted human epiderm (4 layers)

% of Si diffused

Buffer SILICON 50
solution dosed atomic adsorption
40
PRO-D.S.B. SALICYLIC Ac. (UV) 30
20
By 10 PRO-D.S.B. : 0.14 % silicon
HYDROLYSIS PRO-D.S.B. : 1.4 % silicon
0
PROGRESSIVE DIFFUSION 0

500 1000 1500 2000 2500 3000

Time (min)

• Murine epidermic fraction

Dialysed silicon (%) Dialysed molecule (%)

100 80

75 60

50 40

25 PRO-D.S.B. (1.4 % Silicon) 20 Prosilanol : silicon
10 % PRO-D.S.B. (0.14 % Silicon) Prosilanol : salicylic acid
Reference : salicylic acid

0 500 1000 1500 0 500 1000 1500 2000 2500
0 Time (min) 0 Time (min)

We note :

• a gentle and slow cutaneous hydrolysis
• a SILANOL progressively available, the D.S.B. C without polymerization
• the possibility of having treatments adapted and tolerated by respecting the chronobiological rhythms

EXSYMOL

L ACTIVITIES

Anti-inflammatory properties

In vitro study

IL-1α and IL-1β are recognized by the same receptors and have the same biological activity. Keratinocytes
secrete the two types of IL-1, but especially IL-1α. This synthesis can result from some stimuli : UV irradiation,
thermic or physical aggression, phorbol ester.... giving an inflammation. The experimentations have been carried
out on PRO D.S.B. after hydrolysis.

Inhibition by D.S.B. of IL-1 α production by cultured keratinocytes submitted to UV

CONTROL MEDIUM Inflammation CONTROL MEDIUM + D.S.B. IL-1α inhibition (%)

C "U.V." C 120
Y STIMULATION Y 100
T T
O scheme O 80
K K 60
I I
N N
E E
INFLAMMATION ANTI-INFLAMMATORY
DEVELOPMENT ACTION

Transformed keratinocytes NCTC 2544 in culture in a MEM medium 40 In the intracellular fraction
supplemented with 10% of foetal calf serum are submitted to an UV 20 In the extracellular fraction
irradiation (312 nm, 50 mJ/cm2) with or without D.S.B.

0 10 20 30 40 50

Hydrolysed PRO D.S.B. (mg/l of Silicon)

Thanks to the anti-inflammatory IL-1α produced by the cells is determined by the E.L.I.S.A.
properties of salicylate dimethylsilanediol immunoenzymatic technique.
released after hydrolysis, PRO-D.S.B. is an Intracellular IL-1α represents the stimulus influence on cells.
active of choice in the formulation of The curve here above clearly confirms that D.S.B. released
soothing cosmetic products. after hydrolysis of PRO-D.S.B. inhibits the IL-1α production
Besides, it possesses all the properties due by the keratinocytes submitted to an inflammatory stress. This
to the SILANOL’ structure : moisturizing effect is significant and dose-dependent.
and repairing, seeing that silicon is an
essential element for the connective tissue Anti-free radical properties
structure.
The PRO-D.S.B. because to its last We have evaluated the SILANOL ability, obtained after
minute biodisponibility has a high hydrolysis, to inhibit the desoxyribose oxidation into MDA
content of Si-OH and induces a (malondialdehyde) by the free radical OH° generated by the
regulatory and cytostimulative activity Hypoxanthine/Xanthine oxidase enzymatic system. The
at the metabolic level. It is capable of reaction is quantified by spectrophotometry : O.D. reading at
stopping or reversing some degenerative 532 nm.
processes.

Scavenging effect of hydrolysed PRO-D.S.B. (contains salicylic acid 4 mM)

D.S.B. C generated by the PRO-D.S.B. OD 532 nm
possesses a free radical scavenging effect.

PRO-D.S.B. under the hydrolysed form 0.5 Control
possesses an anti-free radical activity, as we can 0.4
see it on the opposite diagram. This activity 0.3 Salicylate (4mM)
expresses itself in a important way as compared 0.2 Silymarine (0.25 mM)
to the silymarine which is a flavonoid mixture. 0.1 Hydrolysed
We observe that the salicylate radical fully PRO-D.S.B. (4 mM)
plays its role of scavenger.
Time (min)

0 2 4 6 8 10

EXSYMOL

Tolerance study

Tests carried out in vivo show that the product is neither toxic nor irritating at the recommended dosage. These
tests consist in studying :

- the oral acute toxicity on mice,
- ocular irritation on rabbit,
- primary cutaneous irritation on rabbits,
- cutaneous irritation by repeated applications on rabbits,
- sensibilizing power on healthy volunteers,
- photosensitization on healthy volunteers (phototoxicity and photoallergy).

We have also studied the tolerances by alternative methods (study of cutaneous and ocular tolerance potential)
carried out in vitro either on cell culture, or on a reconstituted epidermis. The ocular tolerance potential is
evaluated by the cytotoxicity study on cultured fibroblasts isolated from rabbit-cornea. The cutaneous tolerance
potential is evaluated on reconstituted epidermis by an evaluation of the cell viability after 24 hours of contact
with the product.

Formulation

PRO-D.S.B. is a stable solution at 10% of active in the octyl palmitate or other ester. It must imperatively be
formulated without water of alcohol. The recommended concentration is on an average of 0.2 to 1%, but it
must reach 3 or 4% in the anti-hair loss formulations.

Studies carried out

Technical document

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Diffusion study at the cutaneaous level with the hydrolysis
diagram and the biodisponibility confirming the activities here

under quoted

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Anti-free radical activity

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Evaluation of the in vitro anti-inflammatory power of SILANOL,
formed after hydrolysis
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Interest of a prosilanol : curative and preventive effect of
Pro-D.S.B. formulated in a lipophilic serum

*

Tolerances

(acute toxicity, evaluation of the tolerance on man, alternative methods)

EXSYMOL S.A.M. - 4 avenue du Prince Héréditaire Albert - MC 98000 MONACO
Tél. : +377 92 05 66 77 - Fax : +377 92 05 25 02

E-mail : [email protected] - Internet : http://www.exsymol.com