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PhytoCellTec Solar Vitis
Pros_PCTec-SolarVitis_u.qxp:PCTec_SolarVitis_Pros_u 26.2.2010 15:31 Uhr Seite 2
A Revolutionary Technology to Protect Skin StemCells against UV-induced AgingPhytoCellTec Solar Vitis is a powder based on the stem cells of a rare red-flesh grape tolerant to strong UV radiation.
UV radiation is responsible for 80 % of face aging. Despitethe use of sun filters, toxins and oxidants are generatedby UV in the skin. This affects the most sensitive cells suchas the epidermal stem cells which are rare and essential.Thus, their protection against UV stress is of great impor-tance.
A rare grape cultivar of Gamay was selected. Stem cellsfrom this cultivar were obtained using our PhytoCellTectechnology and were then incorporated in a water-solublepowder. These grape stem cells contain special epige-netic factors and metabolites which are able to protecthuman skin stem cells against UV radiation.
Using a novel Progenitor Cell Targeting technology,PhytoCellTec Solar Vitis was shown to: help the skin stem cells to maintain their stem cell
characteristics protect these precious cells against UV-induced stress.Besides, a clinical study showed the capacity of Phyto-CellTec Solar Vitis to increase the tolerance of the skinto UV.
PhytoCellTec Solar Vitis can thus protect both the skinand the epidermal stem cells against the stresses inducedby UV, the main aging factor.
Claim Ideas for PhytoCellTec Solar Vitis Protects skin stem cells against UV stress Increases the skins UV tolerance Fights photo-aging For a vital and healthy-looking skin
Applications Advanced stem cell cosmetic formulas Face and body care to protect the most valuable
skin cells, the stem cells Daily skin care to prevent photo-aging
Formulating with PhytoCellTec Solar Vitis Recommended use level: 0.4 1 % Incorporation: Dissolve PhytoCellTec Solar Vitis
into the aqueous phase or add pre-solved, during thecooling phase (
High Anthocyanin Content in a Rare Grape PhytoCellTec Solar Vitis is based on the stem cells ofthe Gamay Teinturier Fraux grape.
This cultivar, originating from the Burgundy region inFrance, is characterized by its red flesh and juice due tothe extremely high anthocyanin content.
Most red grape varieties have white flesh under their skin but in the case of the Gamay Teinturier Fraux,anthocyanin pigments are also present in the pulp.
Anthocyanins are powerful antioxidants and free radicalscavengers. They act as a sunscreen by absorbing UVradiation. Their effectiveness is further enhanced byinteraction with other phytochemical substances presentin the grape.
The high level of tannins also gives an undesirable tasteto wines. This variety has therefore, almost completelydisappeared.
PhytoCellTec Solar VitisA grape cultivar with a high self-protecting power
Pros_PCTec-SolarVitis_u.qxp:PCTec_SolarVitis_Pros_u 26.2.2010 15:31 Uhr Seite 4
Protection of Stem Cells is Essential Our skin contains stem cells which are located in the basal layer of the epidermis.Their main functions are to replenish and maintain thebalance of cells within the skin as well as to regeneratedamaged tissues.
Epidermal stem cells are thus: essential for the renewal and repair of the skin the unique source of keratinocytes.
Therefore, their protection is of great importance.
Skin Stem Cells and UV RadiationUV radiation which generates toxins and reactive oxygenspecies (ROS) in the skin, is responsible for 80 % of faceaging.
Despite the use of sun filters, toxins and ROS are stillgenerated by UV in the skin. This affects the most sensi-tive cells such as the epidermal stem cells. That is why the protection of skin with sun filters is insufficient.
Skin Stem Cells and UV Stress
Reflection
Absorption
Epid
erm
isD
erm
is
Rad
iatio
nRO
S +
tox
ins
Sun cream with UV-filters
Keratinocyte
Epidermal stem cell
Basal layer
Basement membrane
PhytoCellTec Solar VitisUV can affect epidermal stem cells
Pros_PCTec-SolarVitis_u.qxp:PCTec_SolarVitis_Pros_u 26.2.2010 15:31 Uhr Seite 5
Skin Repair is Controlled by Epidermal Stem CellsUV radiation generates free radicals in the skin which canprovoke erythema and affect the activity of epidermalstem cells leading to photo-aging.
Because epidermal stem cells control skin repair, preserv-ing these precious cells is essential to protect the wholeskin against UV-induced damage.
Plant Stem Cells for Skin Stem CellsAll stem cells, independent of their origin (plant, animal or human) contain specific epigenetic factors whosefunction is to maintain the self-renewal capacity of stemcells. Therefore the Solar Vitis stem cells are used to helpto preserve the vitality of human skin stem cells.
Double Protection against UV-induced DamageThanks to the grape stem cells, PhytoCellTec Solar Vitispreserves the vitality of skin stem cells.
Besides, due to the strong antioxidant power of theGamay Teinturier Fraux grape, PhytoCellTec SolarVitis protects the skin cells and notably the epidermalstem cells against UV-induced stress.
PhytoCellTec Solar VitisGrape stem cells to protect epidermal stem cells
Mechanism of PhytoCellTec Solar Vitis
UV
Radical formation
Photo-aging
Erythema
Cell damage
Depletion ofstem cell activity
Reduced cellregeneration
Strongantioxidantactivity
Epigenetic factorsactivate stem cellfunction
Pros_PCTec-SolarVitis_u.qxp:PCTec_SolarVitis_Pros_u 26.2.2010 15:31 Uhr Seite 6
PhytoCellTec by Mibelle BiochemistryMibelle Biochemistry has developed a novel technologycalled PhytoCellTec, enabling the large scale cultivationof cells from rare and endangered plant species.
This technology is based on the unique totipotency ofplant cells that is to say: the capacity of every plant cell to regenerate new
organs or even the whole plant the capacity of every plant cell to dedifferentiate and
become a stem cell.
Our PhytoCellTec technology relies on the woundhealing mechanism of a plant: part of a plant is woundedto induce the formation of callus cells. This healing tissueconsists of dedifferentiated cells which are stem cells.Callus cells are harvested and cultivated in a suspension.A novel bioreactor system enables the large scale produc-tion.
To obtain the PhytoCellTec Solar Vitis cosmetic ingredi-ent, these stem cells are harvested and homogenized at1200 bar together with phospholipids to encapsulate andstabilize oil- and water-soluble components into liposomes.The resulting extract is carefully sprayed on a powderbased on isomalt.
PhytoCellTec Solar Vitis is thus rich in epigenetic factorsand metabolites which preserve the function of skin stemcells and protect them against UV radiation.
Advantages of PhytoCellTec TechnologyThis innovative technology developed by MibelleBiochemistry offers the following advantages: possibility to cultivate cells of rare and endangered
plants based on small amounts of origin plant material availability of plant material independent of the season
and market demand plant material completely free of environmental pollu-
tants and pesticides constant concentrations of metabolites in the stem cells
PhytoCellTec Solar VitisAdvanced biotechnology to cultivate plant stem cells
PhytoCellTec Solar Vitis Process
Disruption of the stem cells wall and encapsulation of their content into liposome
Spraying on a powder based on isomalt
Liposomal extract
Powder
Preparation of PhytoCellTec Solar Vitis
Wounding of plant material to induce callus formation
Harvesting of developed callus on solid media
Cultivation until complete dedifferentiation to obtain stem cells
Transfer of the stem cells into a suspension (liquid media)
Extract
Preparation of the Solar Vitisstem cells
Pros_PCTec-SolarVitis_u.qxp:PCTec_SolarVitis_Pros_u 26.2.2010 15:31 Uhr Seite 7
Enrichment of Keratinocyte Progenitor Cells Capacity to Form a Colony (CFE)
Progenitor cell (stem cell)
Transient amplifying cell
Differentiated cell
Freshly isolated cells Passage 3 in the specific medium
CD
34
6 Integrin
6% doublelabelled
68% doublelabelled
Preparation of Epidermal Stem CellsA novel Progenitor Cell Targeting technologywas used to prepare human epidermal stem cells.
This technology consists of culturing a skin sample in amedium specifically designed to mimic the micro-environ-ment of the stem cell in the epidermis.
This special, fully defined cell culture medium leads to anenrichment of so called keratinocyte progenitor cells thatcan be considered as stem cells. This enrichment wasquantitatively controlled through FACS (Fluorescence-activated cell sorting) of cells which were labelled withCD34 and 6 integrin, two well-known markers of epider-mal stem cells. Compared to freshly isolated cells, the cellpopulation of passage 3 was characterized by a 10-foldincrease of CD34 / 6 integrin double labelled cells.
The Progenitor Cell Targeting technology provides a cellculture model which specifically enables the evaluation ofthe effects of compounds on epidermal stem cells.
The Capacity to Form a Colony is a Characteristic of Stem CellsStem cells can make identical copies of them-
selves as well as generate specialized cells.They have the capacity to form a colony consisting of: themselves transient amplifying cells (cells in an intermediate state) differentiated cells which have lost the capacity to
divide.
This capacity to form a colony, called CFE (colony-forming efficiency), is a characteristic of stem cells. To measure CFE, cells are seeded at a low density. The number of colonies formed is a value of the concentration of vital progenitor / stem cells.
PhytoCellTec Solar VitisStudy results
Pros_PCTec-SolarVitis_u.qxp:PCTec_SolarVitis_Pros_u 26.2.2010 15:31 Uhr Seite 8
Increase of the Colony-Forming Efficiency (CFE)
Incr
ease
of t
he C
FE c
omp
ared
to
cont
rol i
n %
0.04% 0.15% 0.63% 1.25%
Concentration of Solar Vitis stem cell extract
S-261 / Mibelle AG Biochemistry 2010
0
20
40
60
80
100
Maintenance of Epidermal Stem CellCharacteristics The epidermal stem cells obtained using the
previously described method, were treated with differentconcentrations of the Solar Vitis stem cell extract. Then,the effect of the Solar Vitis stem cell extract on the CFEwas analysed.
Results showed the capacity of the Solar Vitis stem cellextract to strongly increase the CFE: the CFE was stimu-lated by almost 50 % in the presence of 0.04 % Solar Vitisstem cell extract and by almost 80 % in the presence of1.25 % Solar Vitis stem cell extract.
This clearly shows that Solar Vitis stem cell extract helpsthe epidermal stem cells to maintain their stem cellcharacteristics (stemness).
Pros_PCTec-SolarVitis_u.qxp:PCTec_SolarVitis_Pros_u 26.2.2010 15:31 Uhr Seite 9
Protection of Stem Cells against UV Stress
Protection of Epidermal Stem Cells against UV StressThe epidermal stem cells obtained using the
previously described method, were treated with andwithout the Solar Vitis stem cell extract. Some were thenexposed to UVA+UVB-light at 450 kJ/m2 whilst otherswere left unexposed. Afterwards, the CFE was deter-mined.
Results confirmed that the Solar Vitis stem cell extractincreased the CFE of epidermal stem cells.
Results also showed a 58 % decrease of the CFE whenepidermal stem cells were exposed to UV radiation(control). But, the presence of the Solar Vitis stem cellextract could completely counteract the negativeeffect of UV on these cells: the CFE remained at thesame level.
This clearly shows that Solar Vitis stem cell extract pro-tects epidermal stem cells against UV-induced stress.
PhytoCellTec Solar VitisStudy results
Col
ony-
Form
ing
Effi
cien
cy (C
FE) i
n %
without UV with UV
Control Solar Vitis stem cell extract
S-245 / Mibelle AG Biochemistry 2010
0
50
100
150
200
Pros_PCTec-SolarVitis_u.qxp:PCTec_SolarVitis_Pros_u 26.2.2010 15:31 Uhr Seite 10
Protection of the Skin against UV-induced StressThe capacity of PhytoCellTec Solar Vitis to
protect the skin against UV-induced stress was evaluatedby determining its influence on the minimal erythemaldose (MED). MED is the lowest amount of UV that pro-duces skin redness 24 hours after exposure. This is thus avalue of the stress induced by UV on skin.
MED was determined by assessing visually skin redness24 hours after UV radiation using a sun simulator. At the beginning of the study, MED was determined on
the untreated skin of 20 volunteers aged from 19 to 63. Then, the test areas were treated once with a SPF 10
cream with and without 0.4 % PhytoCellTec Solar Vitis. Afterwards, the skin was irradiated with UV doses whose
intensities were in the range of the MED multiplied bythe SPF.
24 hours later, the redness of the skin was evaluatedagain.
Results showed that PhytoCellTec Solar Vitis signifi-cantly increased the MED compared to the placebo: The skin tolerated a 25 % higher UV dose, which corre-sponds to an increase of the SPF from 10 to 13.
PhytoCellTec Solar Vitis can thus protect the skinagainst UV-induced stress.
Increase of UV Tolerance
Placebo(SPF 10 cream)
+0.4 %PhytoCellTecSolar Vitis
10xMED+ 25%
10xMED- 25%
10xMED + 25%
Incr
easi
ng U
V d
ose
S-268 / Mibelle AG Biochemistry 2010
Pros_PCTec-SolarVitis_u.qxp:PCTec_SolarVitis_Pros_u 26.2.2010 15:31 Uhr Seite 11
Claim Ideas for PhytoCellTec Solar Vitis Protects skin stem cells against UV stress Increases the skins UV tolerance Fights photo-aging For a vital and healthy-looking skin
Applications Advanced stem cell cosmetic formulas Face and body care to protect the most valuable skin cells, the stem cells Daily skin care to prevent photo-aging
Marketing Benefits Plant stem cells to protect skin stem cells (patent pending) Proven efficacy on skin stem cells
Mib
elle
AG
Bio
chem
istr
y, 5
033
Buc
hs/S
witz
erla
nd, P
hone
+41
(0)6
2 83
617
31,
info
@m
ibel
leb
ioch
emis
try.
com
, ww
w.m
ibel
leb
ioch
emis
try.
com
PhytoCellTec Solar VitisProtects epidermal stem cellsagainst UV damage
The information contained in this publication is provided in good faith and is based on our current knowledge.No legally binding promise or warranty regarding the suitability of our products for any specific use is made.Claim ideas are offered solely for your consideration, investigation and verification. Mibelle Biochemistry will notassume any expressed or implied liability in connection with any use of this information.
Pros_PCTec-SolarVitis_u.qxp:PCTec_SolarVitis_Pros_u 26.2.2010 15:31 Uhr Seite 12
PhytoCellTec Solar Vitis
PhytoCellTecTM
SolarVitis
80%
PhytoCellTec
PhytoCellTecTM
Solar Vitis
PhytoCellTecTM
Solar Vitis
-
-
PhytoCellTecTM
Solar Vitis
PhytoCellTecTM
Solar Vitis
0.4-1%
PhytoCellTecTM
Solar Vitis
(
20%)
PhytoCellTec Solar Vitis
PhytoCellTecTM
Solar Vitis
Teinturier Fraux
Teinturier Fraux
Ep
iderm
isD
erm
is
Rad
iati
on
RO
S +
to
xin
s
Sun cream with UV-filters
Epidermal stem cell
Basal layer
Basement membrane
Reflection
Absorption
Keratinocyte
PhytoCellTec Solar Vitis
ROS
80%
+
Depletion of
stem cell activity
Strong
antioxidant
activity
Epigenetic factors
activate stem cell
function
Reduced cell
regenerationCell damage
Erythema
Photo-aging
Radical formation
UV
PhytoCellTec Solar Vitis
PhytoCellTecTM
Solar Vitis
Teinturier Fraux
PhytoCellTecTM
Solar Vitis
PhytoCellTecTM
Solar Vitis
Wounding of plant material to induce callus formation
Harvest ing of developed calluson solid media
Cult ivat ion until complete dedifferent iat ion to obtain stem cells
Transfer of the stem cells into a suspension (liquid media)
Disrupt ion of the stem cells wall and encapsulat ion of their
content into liposome
Spraying on a powder based on isomalt
Preparationof the
Solar Vitis stem cells
Preparationof
PhytoCellTec Solar Vitis
Extract
Liposomal extract
Powder
PhytoCellTec Solar Vitis
PhytoCellTecTM
PhytoCellTecTM
PhytoCellTecTM
PhytoCellTecTM
Solar Vitis
( 1200 bar)
PhytoCellTecTM
PhytoCellTecTM
Solar Vitis
PhytoCellTecTM
Solar Vitis
Progenitor (Stem cell)
Transient amplifying cell
Differentiated cell
PhytoCellTec Solar Vitis
(
)
(FACS)
- CD34 6
(CD34 6)
10
()
()
CFE(
) CFE
/
()
(CFE)
6%
68%
0
20
40
60
80
100
0.04% 0.15% 0.63% 1.25%
Incr
ease
of th
e C
FE
co
mp
are
d t
o c
ontr
ol
in %
Concentration of Solar Vitis stem cell extract
PhytoCellTec Solar Vitis
PhytoCellTecTM
Solar Vitis
PhytoCellTecTM
Solar Vitis
(CFE)
PhytoCellTecTM
Solar Vitis
CFE 0.04% PhytoCellTecTM
Solar Vitis CFE 50%
1.25%PhytoCellTecTM
Solar Vitis
CFE 80%
PhytoCellTecTM
Solar Vitis
S-261/ Mibelle Biochemistry 2010
(CFE)
PhytoCellTecTM
Solar Vitis
%
(
)
S-261 / Mibelle AG Biochemistry 2010
0
50
100
150
200
Co
lony-
Fo
rmin
g E
ffic
iency
(C
FE
) in
%
Control Solar Vitis stem cell extract
without UV with UV
PhytoCellTec Solar Vitis
1) PhytoCellTecTM
Solar Vitis
2) PhytoCellTecTM
Solar Vitis
(1)(2)
450KJ/M2 UVA+UVB
CFE
PhytoCellTecTM
Solar Vitis
CFE
CFE 58%
PhytoCellTecTM
Solar Vitis
CFE
PhytoCellTecTM
Solar Vitis
S-245/ Mibelle Biochemistry 2010
PhytoCellTecTM Solar Vitis
C
FE
%
+25%
+ 0.4%
PhytoCellTec
Solar Vitis
Placebo
(SPF 10 cream)
S-268
10xMED
10xMED - 25%
10xMED + 25%
Incre
asi
ng
UV
do
se
PhytoCellTec Solar Vitis
MED
PhytoCellTecTM
Solar Vitis
MED
24
24
MED
20 19-63
MED
1) 0.4% PhytoCellTecTM
Solar Vitis
SPF 10
2) PhytoCellTecTM
Solar Viti
SPF 10
= MED XSPF
24
PhytoCellTecTM
Solar Vitis
MED
25% SPF
10 13
PhytoCellTecTM
Solar Vitis
S-268/ Mibelle Biochemistry 2010
SPF
10
PhytoCellTec Solar Vitis
PhytoCellTecTM Solar Vitis
The information contained in this publication is provided in good faith and is based on our current knowledge. No legally binding promise or warranty regarding the suitability of our products for any specific use is made. Claim ideas are offered solely for your consideration, investigation and verification. Mibelle Biochemistry will not assume any expressed or implied liability in connection with any use of this information.
Patent Number: US2008/0299092 A1 EP 1985280 A2
PhytoCellTec