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HYDRANOV
A New Look at Hydration
HYDRANOV
A New Look at Hydration
COSMOS
EPIDERMIS SYNTHESIZES 4 TIMES MORE HYALURONIC ACID THAN THE DERMIS.
Epidermal hyaluronic acid: a still overlooked potential.
The rate of hyaluronic synthesis is higher in the epidermis than in the dermis. Since the dermis is much thicker than the
epidermis, it contains 4 to 9 times more hyaluronic acid, but for equivalent tissue quantities, the epidermis synthesises 4
times more hyaluronic acid than the dermis (1).
In the epidermis hyaluronic acid is localised in the intercellular space of the basal and spinous layers. In the same way as in
the dermis the hygroscopic properties of hyaluronic acid are of great importance in hydrating the deep layers of the epidermis,
but its function goes further than conventional hydration. It has been shown that the presence of high concentrations of
hyaluronic acid in the intercellular space tends to renew desmosomes and tight junctions, and so reorganise the keratinocytes
not only within the basal layer, but also throughout the process of differentiation as far as the stratum corneum (2). Hyaluronic
acid acts therefore like an overall epidermal restructuring agent by initiating and maintaining constant cellular remodelling
from the basal layer to the cornified layer.
« HYALURONIC LIKE », HYDRANOV HAS HYGROSCOPIC PROPERTIES ALLOWING THE CAPTURE OF
WATER MOLECULES AT THE SKIN SURFACE. « EPIDERMAL HYALURONIC ACTIVATOR », IT ALSO
STIMULATES THE SYNTHESIS OF EPIDERMAL HYALURONIC ACID FOR AN OVERALL EPIDERMAL
RESTRUCTING AND HYDRATING ACTION.
HYDRANOV :
High Tech Concentrate of Oligofurcellaran
The oligofurcellaran is obtained by the depolymerisation of a sulfated furcellaran (galactose and anhydrous galactose) coming
from the red alga Furcellaria lumbricalis, widespread in Scandinavian waters.
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,
induces a double helicale reorganization of the polymer that gives it hygroscopic and gelling properties comparable to
hyaluronic acid. The resulting oligofurcellaran has a molecular weight >200kDa.
This depolymerisation method, water and acid free, complies with the policy of energetic resources managment developped
by Codif R&N.
HYDRANOV CHRONOLOGICAL ACTION
1 ‐ « hyaluronic like » action at the surface of the skin
2 ‐ « hyaluronic activator » action : stimulates the synthesis of epidermal hyaluronic acid
3 ‐ Reinforcement of tight junctions – New target : Claudin 1
4 ‐ Stimulation of ceramids synthesis
5 ‐ Reinforcement of NMF – New target : Filaggrin
“HYALURONIC LIKE” ACTION OF HYDRANOV
IN‐VITRO TEST
The oligofurcellaran concentrated in Hydranov has high molecular weight. Therefore in the same way as hyaluronic acid it
acts as a macromolecule with surface properties.
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.
120 ‐
Hyaluronic Acid
mass gain % at equilibrium
100 ‐
Hydranov
80 ‐
60 ‐
40 ‐
40
60
% of relative humidity
‐
20
‐
0
‐
‐
0
‐
20 ‐
80
100
RESULT:
Hydranov is able to trap atmospheric water molecules following a kinetic totally comparable to hyaluronic acid. The more
atmosphere is saturated with water, the more 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.
“HYALURONIC ACTIVATOR” ACTION OF HYDRANOV
Given the size of the oligofurcellaran and the low probability that it can penetrate into the epidermis, the effect of Hydranov
has been evaluated by topical application on human skin explants or human reconstructed epidermis.
HYDRANOV INCREASES THE EXPRESSION OF HYALURONAN SYNTHASE 3
PROTOCOL:
Reconstructed human epidermis ‐ Topical application of
1% Hydranov for 72 hours. Gene expression analysis using
RT‐qPCR.
RESULT:
+64% HYALURONAN SYNTHASE 3
180 ‐
160 ‐
140 ‐
+64%
120 ‐
100 ‐
80 ‐
60 ‐
40 ‐
20 ‐
0
‐
Hyaluronan synthase 3 is an enzyme involved in hyaluronic
acid synthesis.
expression % compared to untreated control
EX‐VIVO TEST
Control
1% Hydranov
HYDRANOV INCREASES THE SYNTHESIS OF EPIDERMAL HYALURONIC ACID
EX‐VIVO TEST
PROTOCOL:
Human skin explants ‐ Topical application of 1.5%
Hydranov for 9 days. Quantification of epidermal
hyaluronic acid synthesis using immuno‐labelling (fuchsia
colour).
RESULT:
+211%** HYALURONIC ACID
X3 : TOTAL SURFACE AREA OCCUPIED BY HYALURONIC ACID
Untreated explant
**p<0.01 Student test
Explant treated with 1.5% Hydranov
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.
RESTRUCTURING ACTION OF HYDRANOV :
CLAUDIN 1 ET CERAMIDS
The function of tight junctions is to block circulation of fluids
between cells and to ensure in this way that there is a tight seal
between two tissue compartments. They were identified in
human skin explants in the medium layers (granular and sub‐
basal layers)(3). The main factor contributing to the formation
of these tight junctions is a protein called Claudin 1.
In 2002, Furuse and al. showed that mice which did not
express Claudin 1 died of massive Trans‐Epidermal Water Loss
due to a deficient barrier function in the granular layer (4).
Tight junction:
protein complex
Lipid bilayer
Claudine
Tight junction
HYDRANOV STIMULATES THE SYNTHESIS
OF CLAUDIN 1
EX‐VIVO TEST
PROTOCOL:
Human skin explants – Topical application of 1.5% Hydranov
for 9 days. Quantification of Claudin 1 synthesis using
immuno‐labelling.
RESULT:
+45% CLAUDIN 1
expression % versus untreated control
Claudin 1
160 ‐
140 ‐
+45%
120 ‐
100 ‐
80 ‐
60 ‐
40 ‐
20 ‐
‐
0
Control
1.5% Hydranov
HYDRANOV STIMULATES THE SYNTHESIS
OF CERAMIDS
EX‐VIVO TEST
PROTOCOL:
Human skin explants – Topical application of 1.5% Hydranov
for 9 days. Quantification of Ceramids synthesis using
immuno‐labelling.
Untreated explant
RESULT: :
+56%** CERAMIDS
**p<0.01 Student test
Explant treated with 1.5% Hydranov
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.
NMF BOOSTER EFFECT OF HYDRANOV
Filaggrin
Procaspase 14 maturation
EX‐VIVO TEST
PROTOCOL:
Reconstructed human epidermis ‐ Topical application of 1%
Hydranov for 72 hours. Gene expression analysis using RT‐
qPCR.
RESULT:
+43% FILAGGRIN
Hygroscopic AA
Caspase 14
activation
KLK5
160 ‐
140 ‐
120 ‐
+43%
100 ‐
80 ‐
60 ‐
40 ‐
20 ‐
0
‐
HYDRANOV STIMULATES THE SYNTHESIS
OF FILAGGRIN
degradation
KLK7
expression % versus untreated control
Numerous studies report the essential role of Filaggrin which,
when it is broken down in the stratum corneum, adds
hygroscopic amino acids (AA) to the NMF (Natural
Moisturizing Factors). An absence of filaggrin expression leads
to an almost complete lack of stratum corneum (ichtyosis) and
major skin dehydration (xerosis) (5).
Filaggrin is broken down in the stratum corneum by
Caspase 14 which is itself matured under the control of a
serine protease called kallikrein‐related peptidase 7 (KLK7).
Activation of KLK7 depends on a second kallikrein coded by
the gene KLK5
Control
1% Hydranov
HYDRANOV FAVOURS FILAGGRIN DEGRADATION
EX‐VIVO TEST
PROTOCOL:
Reconstructed human epidermis – Topical application of 1%
Hydranov for 24 hours (KLK5 and KLK7 analysis) and 72 hours
(caspase 14 analysis). Analysis of genes expression using RT‐
qPCR. Visualization of Caspase 14 using immuno‐labelling
(fuchsia colour) in human skin explant treated with 1.5%
Hydranov.
Visualization of Caspase 14 in untreated
explant
RESULT:
+60% KLK5 / +39% KLK7
+65% CASPASE 14
Visualization of Caspase 14 in explant
treated with 1.5% Hydranov
BY FAVOURING FILAGGRIN BREAKDOWN, HYDRANOV BOOSTS NMF AND REINFORCES THE
HYDRATION OF CORNIFIED LAYER. THIS LATEST PROPERTY COMPLETES HYDRANOV ACTION:
A GLOBAL HYDRATION FROM THE BASAL LAYER TO THE STRATUM CORNEUM.
NMF
COMPARATIVE HYDRATING PROPERTIES
OF HYDRANOV AND HYALURONIC ACID
IN‐VIVO TEST
PROTOCOL:
15 volunteers apply a solution containing 1.5% HYDRANOV (equivalent to 0.009% pure oligofurcellaran)
15 volunteers apply a solution containing 0,025% pure HYALURONIC ACID (% recommended by the supplier) of high molecular
weight: >200kDa.
Twice daily applications for 2 weeks on forearms
Measure of skin hydration level using corneometer
Hydranov hydrates the skin with an immediate and
continuous efficacy during the 24 hours following its
application.
Its hydrating action is faster and higher than thus of
Hyaluronic acid.
HYDRATION INCREASE INDUCED BY HYDRANOV IS 3 TIMES
HIGHER THAN THUS TRIGGERED BY HYALURONIC ACID.
*p<0.05 Student test
Hydration variation versus T0 (%)
COMPARATIVE EFFICACY AFTER A SINGLE APPLICATION
18 ‐
Hydranov
16 ‐
Hyaluronic acid
14 ‐
12 ‐
*
10 ‐
8‐
6‐
*
*
4‐
‐
0
‐
2‐
4H
6H
24H
*p<0.05 Student test
Hydranov
16 ‐
Hyaluronic acid
*
14 ‐
12 ‐
10 ‐
*
*
*
8‐
6‐
4‐
2‐
0
D1
‐
AFTER A 2 WEEKS TREATMENT, THE HYDRATION PROVIDED
BY HYALURONIC ACID IS STILL LOWER THAN THUS PROVIDED
BY HYDRANOV AFTER ONLY 24H.
18 ‐
‐
Hydranov has a cumulative hydrating effect. Day after day,
skin hydration is increased.
Hydration variation versus T0 (%)
COMPARATIVE EFFICACY AFTER 2 WEEKS
D7
D14
VISUALIZATION OF THE RESTRUCTURING ACTION OF HYDRANOV
EX‐VIVO TEST
PROTOCOL:
Human skin explants.
Topical application of 1.5% Hydranov for 1 week.
Staining, rinsing, drying and observation of the surface using Scanning Electron Microscopy.
Untreated explant
Explant treated with Hydranov
THE EXPLANT TREATED WITH HYDRANOV HAS AN HOMOGENEOUS 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.
CONCLUSION :
HYDRANOV targets a molecule with outstanding potential and little known: the epidermal hyaluronic
acid.
Hydranov reinvents hydration by targeting new molecules with unexploited potential. By increasing
the synthesis of epidermal hyaluronic acid, Hydranov promotes not only hydration of the deepest
layers of the epidermis, but also renewal of tight junctions to reorganise the keratinocytes in all the
layers of the epidermis. In the corneal layer, Hydranov activates metabolism of filaggrin to enrich NMF
with hygroscopic amino acids while on the surface, in the same way as hyaluronic acid, it captures
water molecules to maintain a hydrating film.
Hydranov is a Hi‐Tech concentrate of oligofurcellaran, faster and 3 times more efficient than hyaluronic
acid to hydrate and restructure the skin.
Marine plant origin
Hydrosoluble active
ingredient
In‐vitro test
ex‐vivo test
In‐vivo test
COSMOS
Cosmos Validation
FORMULATION GUIDELINE
HYDRA‐RESTRUCTURING FLUID
This fluid is formulated with HYDRANOV: hydra‐restructuring ingredient, HYDROFILTRAT MENYANTHES G: dermo‐
restructuring active and a moisturizing ingredient: PHEOHYDRANE.
Phase
Raw material / commercial name
INCI name
%
NIKKOMULESE LC (1)
Behenyl Alcohol & Stearyl Alcohol & PEG‐20 Phytosterol & Cetyl Alcohol & Phytosterols
& Glyceryl Stearate & Hydrogenated Lecithin & Caprylic/Capric Triglyceride
5
CRODAMOL GTCC / MIGLYOL 812 / WAGLINOL (2)
Caprylic/Capric Triglyceride
3
SILICON (DIMETHICONE (100CS) (3)
Dimethicone
0.5
PHENOXYETHANOL (4)
Phenoxyethanol
0.8
ARLAMOL HD (5)
Isohexadecane
4
LANOL 99 (6)
Isononyl Isononanoate
5
DEMINERALIZED WATER
Aqua
AVICEL PC 611 (7)
Microcrystalline Cellulose & Cellulose Gum
1
DIPROPYLENE GLYCOL (8)
Dipropylene Glycol
3
KELTROL CGSFT (9)
Xanthan Gum
0.5
ELESTAB CPN (10)
Chlorphenesin
0.27
HYDRANOV P (11)
Aqua & Phenoxyethanol & Sodium Carrageenan & Maris 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
FRAGRANCE FLOWER AND FRUIT 0217350 (12)
Fragrance
A
72.33
B
B’
B’’
C
(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
Product Aspect: White Glitter Fluid cream
Product Properties: pH = 6.54 ± 0.5
Operating Method:
• Heat A at 75°C
• Heat the phase B at 75°C under emulsifier 2000 rpm during 10 minutes.
• Add the mixture B´ under emulsifier 1500 rpm during 5 minutes.
• Add the mixture B’’ under emulsifier 1500 rpm during 5 minutes.
• Add A into B+B’+B’’ under emulsifier 2500 rpm, then let shake in these conditions during 10 minutes.
• Around 25‐30°C, add the phase C.
0.1
BIBLIOGRAPHIC REFERENCES
(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
(2) Tammi R, Tammi M: Hyluronan in the Epidermis ‐ http://glycoforum.gr.jp/science/hyaluronan/HA04/HA04E.html
(3) 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
(4) 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.
(5) Filaggrin in the frontline: role in skin barrier function and disease. Sandilands A, Sutherland C, et al. J Cell Science,
2009, 122, 1285‐1294
HYDRANOV - A NEW LOOK AT HYDRATION
Cosmetic activities
• « hyaluronic like » action: traps water molecules at the surface of the skin
• « hyaluronic activator » action : stimulates the synthesis of epidermal hyaluronic acid
• Reinforces tight junctions via Claudin 1
• Increases ceramids synthesis
• Reinforces the NMF via Filaggrin
• Hydrating efficacy faster and higher than hyaluronic acid
• Restructuring action
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
COSMOS
Recommended % of use: Hydranov P : 1.5% ‐ Hydranov PA : 1.5%
Technical department : infotech@codif‐recherche‐et‐nature.com
Commercial department : commercial@codif‐recherche‐et‐nature.com
70, rue du Commandant l’Herminier ‐ CS11781 ‐ 35417 Saint‐Malo cedex ‐ FRANCE
Tel : +33‐2‐23‐18‐31‐07 Fax : +33‐2‐23‐18‐31‐01
www.codif‐recherche‐et‐nature.com
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