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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
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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
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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/