NEW TARGET

EPIDERMALHYALURONIC ACID

HYDRANOV

Hyaluronic acid is quite famous for its hydratingand filling properties in the dermis. But whatabout hyaluronic acid in epidermis?

Dermis is much thicker than epidermis, andcontains 4-9 times more hyaluronic acid.

But for equivalent amount of tissue, epidermissynthesizes 4 times more hyaluronicacid than the dermis (1).

In epidermis, hyaluronic acid is located in theintercellular space of the basal and spinous layers.It plays a major role in the architecture of thewhole epidermis

EPIDERMAL HYALURONIC ACID

A potential still unexploited

Epidermal Hyaluronic Acid

(1) Tammi M, Saamanen AM : Degradation of Newly Synthesized High Molecular Mass Hyaluronan in the Epidermal and Dermal Compartments of Human

Skin in Organ Culture. J Invest Dermatol 97: 126-130, 1991

1- HYDRATION OF DEEPER LAYERS OF EPIDERMIS

2- RESTRUCTURING ACTION

A high concentration of hyaluronic acid in theintercellular space triggers a renewal ofdesmosomes and tight junctions and therefore aconstant rearrangement of keratinocytes (2).

Epidermal hyaluronic acid is a global restructuringagent of the epidermis. It initiates and maintains aconstant cellular remodeling from the basal layerto the stratum corneum.

EPIDERMAL HYALURONIC ACID

Its role in epidermis

Epidermal Hyaluronic Acid

Desmosomes

Tight junctions

(2) Tammi R, Tammi M: Hyluronan in the Epidermis

http://glycoforum.gr.jp/science/hyaluronan/HA04/HA04E.html

« HYALURONIC LIKE »

Like hyaluronic acid, Hydranov has hygroscopic

properties to capture water molecules on the surface of

the skin.

« EPIDERMAL HYALURONIC ACTIVATOR »

Hydranov stimulates the synthesis of epidermal

hyaluronic acid for a restructuring and hydrating action

on the whole epidermis.

HYDRANOV : A HI-TECH CONCENTRATE OF

OLIGOFURCELLARAN

The oligofurcellaran is obtained by the depolymerisation

of a sulfated furcellaran coming from the red alga

Furcellaria lumbrilicalis, widespread in Scandinavian

waters.

HYDRANOV

“Hyaluronic Like” & “Epidermal Hyaluronic Activator”

Furcellaria lumbrilicalis

5

HYDRANOV

Hi-Tech concentrate of Oligofurcellaran

The oligofurcellaran is obtained by depolymerization of a

sulfated furcellaran: galactose and anhydrogalactose.

Depolymerization is made using supercritical CO2 technology

in anhydrous conditions. After depolymerization, the

oligofurcellaran is rehydrated with an enriched sea salt

solution. This final intake of marine nutrients, and mainly

potassium, induced a double helicale reorganization of the

polymer that gives it a gelling property comparable to a

hyaluronic acid. The size of the resulting oligofurcellaran is

roughly 200 kDa.

No solvent + mastering of water and energy consumption

= ecofriendly active ingredient

FURCELLARIA LUMBRILICALIS

POWDER OF SULFATED

FURCELLARAN

POWDER OF HYDROLYZED

FURCELLARAN

HYDRANOV

Water extraction

and drying

Subcritical CO2

extraction

Solubilization

(water+sea salts)

HYDRANOV

Hydration strategy

WA

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• « hyaluronic like » action on skin surface

• « epidermal hyaluronic activator » : stimulation

of epidermal hyaluronic acid synthesis

• Reinforcement of tight junctions

New target : Claudin 1

• Stimulation of ceramids synthesis

• Reinforcement of NMF

New target : Filaggrin

HYALURONIC LIKE ACTION

Hygroscopy Comparative Study

The aim of this test is to measure the ability of

Hydranov to capture water molecules and to

compare it with hyaluronic acid.

Protocol:

Pure samples of Hydranov and hyaluronic acid are

put in specific cells with a relative humidity that

will vary from 0 to 95%.

For each condition of relative humidity, the

polymers capture water molecules to reach a

maximum called « gain mass at sorption

equilibrium ».

The value of gain mass reflects the ability of each

polymer to trap water molecules.

HYALURONIC LIKE ACTION

Hygroscopy Comparative Study

RESULT :

Hydranov is able to trap atmospheric water

molecules following a kinetic totally

comparable to thus of hyaluronic acid.

The more atmosphere is saturated with water,

Hydranov traps water molecules. For 95% of

relative humidity, 86% mass gain is measured.

HYDRANOV IS CAPABLE TO TRAP A QUANTITY

OF WATER ALMOST EQUAL TO ITS INITIAL MASS

AND THUS MAINTAINS A MOISTURE FILM ON

THE SURFACE OF THE SKIN.

EPIDERMAL HYALURONIC ACTIVATIONHydranov stimulates the expression of hyaluronan synthase 3.

Protocol:

Topical application of 1% HYDRANOV on human

reconstituted epidermis. Analysis of genes

expression using RT-qPCR after 72 hours.

RESULT

Hyaluronan synthase 3 is responsible for

hyaluronic acid synthesis.

Its expression is increased by 64% in epidermis

treated with 1% HYDRANOV.

1%

EPIDERMAL HYALURONIC ACTIVATIONHydranov stimulates the synthesis of epidermal hyaluronic acid

Protocol:

Topical application of 1.5% HYDRANOV on human skin

explants. Quantification of epidermal hyaluronic acid

synthesis using immuno-labeling after 9 days. Hyaluronic

acid is highlighted in pink-purple.

RESULT

We observe a +211%** significant increase in

epidermal hyaluronic acid synthesis in epidermis

treated with 1.5% HYDRANOV.

1.5%

Untreated explant

Explant treated with Hydranov

EP

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HYDRANOV & HYALURONIC ACID

Increase in epidermal hyaluronic acid synthesis will provide a better hydration of

the deeper layers of the epidermis but also stimulate the renewal of tight

junctions in the middle and upper layers.

DEEPER LAYERS

+ 211% epidermal hyaluronic acid

SKIN SURFACE

« Hyaluronic like » effect

!NEW TARGET!

EPIDERMALHYALURONIC ACID

TIGHT JUNCTIONS

The central role of Claudin 1

The function of tight junctions is to block water

circulation in intercellular spaces and thus to ensure

the seal between two tissues compartments. This

kind of junction has been identified in human skin

explants into the granular layer[2].

The main component of the tight junctions is a

protein named CLAUDIN-1.

In 2002, Furuse and al showed that mice that do

not express claudin-1 died of a massive TEWL due

to a deficient barrier function of granular layer [3].

[2] Adherens Junctions, Desmosomes and Tight Junctions in Epidermal Barrier

Function Johanna M. Brandner, Marek Haftek and Carien M. Niessen. The Open

Dermatology Journal, 2010, 4, 14-20

[3] Claudin-based tight junctions are crucial for the mammalian epidermal barrier:

a lesson from claudin-1-deficient mice. Furuse M, Hata M, Furuse K, et al. J Cell Biol

2002; 156: 1099-111.

TIGHT JUNCTIONSHydranov stimulates the synthesis of Claudin 1

Protocol:

Topical application of 1.5% HYDRANOV on human skin

explants. Quantification of claudin 1 synthesis using

immuno-labeling after 9 days. Claudin 1 is highlighted in

pink-purple.

RESULT

We observe a +45% increase in Claudin-1

synthesis, in epidermis treated with 1.5%

Hydranov.

1.5%

Untreated explant

Explant treated with Hydranov

EPIDERMIS SEALING

Hydranov increases ceramids synthesis

1.5%

Protocol:

Topical application of 1.5% HYDRANOV on human skin

explants. Quantification of ceramids synthesis using

immuno-labeling after 9 days. Ceramids are highlighted

in pink-purple.

RESULT

We observe a +56%** significant increase in

ceramids synthesis, in epidermis treated with

1.5% Hydranov.

This action nourishes the epidermis and

reinforces its tightness.

Untreated explant

Explant treated with Hydranov

Exp

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HYDRANOV AND EPIDERMIS SEALING

Increase in the synthesis of claudin 1 and ceramids helps to strengthen the sealing

of the epidermis. The hydration rate previously increased via epidermal hyaluronic

acid in the deeper layers is preserved.

MEDIUM LAYERS

+ 45% Claudin-1 (tight junctions)MEDIUM LAYERS

+56% ceramids

The main moisturizing component of the

stratum corneum is the NMF, mainly composed

of urea, water and amino acid.

Many studies have reported the important role

of filaggrin which when degraded in the stratum

corneum, enriches the NMF in hygroscopic

amino acids.

A lack of filaggrin expression results in the

virtual absence of stratum corneum (ichtyosis)

and a significant dehydration of the skin

(xerosis) [4].

[4] Filaggrin in the frontline: role in skin barrier function and disease.

Sandilands A, Sutherland C, et al. J Cell Science, 2009, 122, 1285-1294

NMF BOOSTER ACTION

Benefits of Filaggrin

FILAGGRIN

Caspase 14

Histidine Glutamine

Urocanic acid Pyrrolidone

carboxylic acid

NMF

NMF BOOSTER ACTION

Filaggrin metabolism

Profilaggrin is synthesis in the granular layer under the control of the FLG gene. It is then cleaved

into filaggrin that becomes biologically active and allows the aggregation of keratin fibers.

FILAGRINE is then degraded in the stratum corneum by CASPASE 14 whose maturation is under

the control of a serine protease called KALLIKREIN RELATED PEPTIDASE 7 (KLK7). The activation of

KLK7 depends on a second kallikrein encodes by the gene KLK5.

Filaggrin Hygroscopic AA NMFdegradation

Caspase 14Procaspase 14maturation

KLK7

KLK5

activation

NMF BOOSTER ACTION

Hydranov stimulates the synthesis of filaggrin

Protocol:

Topical application of 1% HYDRANOV on human

reconstituted epidermis. Analysis of genes

expression using RT-qPCR after 72 hours.

RESULT

The expression of filaggrin is increased by

43% in epidermis treated with 1%

HYDRANOV. This means that the quantity of

hygroscopic AA obtained through filaggrin

degradation will be also increased.

1%

NMF BOOSTER ACTION

Hydranov stimulates the expression of kallikreins

Protocol:

Topical application of 1% HYDRANOV on human

reconstituted epidermis. Analysis of genes expression

using RT-qPCR after 24 hours.

.

RESULT

The expression of KLK5 and KLK7 is increased in

epidermis treated with 1% HYDRANOV.

1%

NMF BOOSTER ACTION

Hydranov stimulates the expression of Caspase 14

Protocol:

Topical application of 1% HYDRANOV on human

reconstituted epidermis. Analysis of genes

expression using RT-qPCR after 72 hours.

Topical application of 1.5% HYDRANOV on human

skin explants. Visualization of Caspase 14 synthesis

in pink-purple.

RESULT

The expression of Caspase 14 is increased by

+65% in epidermis treated with 1%

HYDRANOV.

1%

Str

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Conclusion on the effects of HYDRANOV from the

basal layer to the surface of the skin

DEEPER LAYERS

+211% Epidermal Hyaluronic acid

MEDIUM LAYERS

+45% Claudin 1 (tight junctions)

+56% Ceramids

CORNIFIED LAYER

+43% Filaggrin / +60% Caspase 14

+39% / 65% KLK 7 & KLK5

SKIN SURFACE

“Hyaluronic Like” Action

HYDRANOV STRATEGY

EP

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CLINICAL TEST

Comparative study of the hydrating effect of

Hydranov and Hyaluronic Acid

Protocol:

• 15 volunteers apply a solution containing 1.5% HYDRANOV

(equivalent to 0.009% pure oligofurcellaran)

• 15 volunteers apply a solution containing 0,025% PUR HYALURONIC ACID

(% recommended by the supplier) of high molecular weight: 2000 kDa

• Twice daily applications for 2 weeks on forearms

• Measure of skin hydration level using corneometer

1.5%

CLINICAL TEST

Hydrating effect of HYDRANOV after a single

application

1.5%

HYDRANOV increases skin hydration

level 4 hours only after a single

application.

Its hydrating action is faster and

more efficient than hyaluronic acid.

*P<0.05 Student test

CLINICAL TEST

Hydrating effect of HYDRANOV after 2 weeks

treatment

1.5%

Day after day, HYDRANOV increases

skin hydration level. It is still more

efficient than hyaluronic acid.

Treatment with hyaluronic acid needs

more than 2 weeks to reach the

hydration level provided by 1 day

treatment with HYDRANOV.

*P<0.05 Student test

Visualisation of Hydranov restructuring effect

1.5%

Protocol:

Human skin explants. Topical application of 1.5%

Hydranov for 1 week. Observation of skin surface

using Scanning Electron Microscopy.

RESULT

Explants treated with Hydranov have an

homogenous and smoothed surface with

only few desquaming cells.

This observation illustrates the restructuring

action of Hydranov on the whole epidermis,

from the basal layer to the cornified layer.

Untreated explant

Explant treated with Hydranov

Conclusion on HYDRANOV

HYDRANOV provides the skin with an overall hydrating and

restructuring action, from the basal layer to the stratum corneum.

IN-VITRO:

Hyaluronic like action to trap water molecules at the skin surface

EX-VIVO:

• Stimulation of epidermal hyaluronic acid synthesis

• Stimulation of claudin-1 synthesis (tight junctions)

• Stimulation of ceramids synthesis

• Stimulation of synthesis and degradation of filaggrin (NMF)

• Restructuring action

IN-VIVO:

Faster and more efficient than hyaluronic acid to hydrate the skin

after a single application but also after 2 weeks daily applications.

HYALURONIC LIKE

HYALURONIC ACTIVATOR

!NEW TARGET!

EPIDERMALHYALURONIC ACID

Conclusion on HYDRANOV

Inci name

HYDRANOV P: Water (and) Phenoxyethanol (and) Sodium Carrageenan (and) Sea salt

HYDRANOV PA: Water (and) Phenethyl alcohol (and) Sodium Carrageenan (and) Sea salt

Recommended % of use: 1.5%

EXAMPLES OF CONCEPT

In a CC CREAM

With Matrigenics. 14G and Neurolight .61G

In a PERFECTIONIST CREAM

With Epidermist 4.0 and EPS Seafill

In a High-Perfomance Hydrating Fluid

With Hydrasalinol

HYALURONIC LIKE

HYALURONIC ACTIVATOR

!NEW TARGET!

EPIDERMALHYALURONIC ACID

OK

CHINA

Phase Raw material / Commercial name INCI name %

A

NIKKOMULESE LC (1)Behenyl Alcohol & Stearyl Alcohol & PEG-20 Phytosterol & Cetyl Alcohol & Phytosterols &

Glyceryl Stearate & Hydrogenated Lecithin & Caprylic/Capric Triglyceride5

CRODAMOL GTCC / MIGLYOL 812 / WAGLINOL (2) Caprylic/Capric Triglyceride 3

SILICONE (DIMETHICONE (100CS)) (3) Dimethicone 0.5

PHENOXYETHANOL (4) Phenoxyethanol 0.8

ARLAMOL HD (5) Isohexadecane 4

LANOL 99 (6) Isononyl Isononanoate 5

B

EAU DEMINERALISEE Aqua 72.33

AVICEL PC 611 (7) Microcrystalline Cellulose & Cellulose Gum 1

B’DIPROPYLENE GLYCOL (8) Dipropylene Glycol 3

KELTROL CGSFT (9) Xanthan Gum 0.5

B’’ ELESTAB CPN (10) Chlorphenesin 0.27

C

HYDRANOV P (11) Aqua & Water (and) Phenoxyethanol (and) Sodium Carrageenan (and) Sea sal 1.5

PHEOHYDRANE P (11) Aqua & Hydrolyzed Algin & Maris Aqua & Phenoxyethanol & Chlorella Vulgaris Extract 1

HYDROFILTRAT MENYANTHES G (11) Glycerin & Aqua & Menyanthes Trifoliata Extract 2

PARFUM FLEUR ET FRUIT 0217350 (12) Parfum 0.1

HYDRA-RESTRUCTURING FLUID

Formulation guidelineThis fluid is formulated with Hydranov, hydra-restructuring ingredient, Hydrofiltrat

Menyanthes G : a dermo-restructuring ingredient, and Pheohydrane, a moisturizer.

1) IMCD, (2) Croda, (3) Quimdis, (4) Laserson, (5) Quimasso, (6) Seppic, (7) FMC BioPolymer, (8) Brenntag, (9) CP Kelco, (10) Cognis, (11) CODIF Recherche et Nature, (12) Expressions parfumées

PROTOCOL

1.Heat A at 75°C

2.Heat B at 75°C under emulsifier 2000 rpm for 10 min

3.Add B´ under emulsifier 1500 rpm for 5 min

4.Add B’’ under emulsifier 1500 rpm for 5 min

5. Introduce A into B+B’+B’’ under emulsifier 2500 rpm, for 10 min.

6. At 25-30°C, add C.

http://www.codif-recherche-et-nature.com/