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DermCom
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Cell2cell communication
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for skin matrix repair


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DermCom
Cell2cell communication for skin matrix repair

A Flower Bulb Extract to Improve Cell-Cell DermCom


­Communication • Boosts collagen and elastin production
Based on a Crocus chrysanthus bulb extract, DermCom • Stimulates natural growth factors of the skin
can reverse the aging process by stimulating the com- • Renews the skin’s resilience and firmness
munication between skin cells. • Reverses aging processes
• Rejuvenates skin texture
The crocus is a universal symbol of rejuvenation and • Visibly reduces stretch marks
youthfulness. Crocus chrysanthus “Cream Beauty” is a
beautiful variety with creamy-colored petals. Bulbs are Applications
plant parts specializing in the storage of nutrients and • Collagen and elastin boosters
so are an interesting source of active ingredients for • Firming and lifting products
­cosmetics. • Repair formulas
• Stretch mark creams
With age, the communication process between skin • Intense anti-aging treatments
cells, which is mediated by growth factors, is reduced.
This strongly affects the extracellular matrix (ECM), the Formulating with DermCom
structural network of the skin and leads to a reduction • Recommended use level: 0.4 – 2 %
of its firmness, elasticity and density. • Incorporation: Dissolve DermCom into the aqueous
phase or add pre-solved (DermCom is easily soluble
DermCom was shown, in a series of tests, to stimulate in water at room temperature) during the cooling
keratinocytes to secrete growth factors that could phase (< 60 °C).
­enhance the synthesis of collagen and elastin in the • Thermostability: Temperatures of up to 60 °C for a
­dermis. This effect on fibroblasts was comparable to short time do not affect the stability of DermCom.
the one of the transforming growth factor (TGF-β), a
­natural growth factor involved in ECM synthesis. INCI (EU / PCPC) Declaration
Crocus Chrysanthus Bulb Extract (and) Acacia Senegal
Clinical studies confirmed this result after only 2 weeks’ Gum (and) Aqua / Water
treatment:
• skin firmness was greatly improved
• the collagen and elastin contents in the skin were both
increased.

In a study involving volunteers with stretch marks,


a cream with DermCom visibly reduced redness and
­increased lightness in stretch mark areas.

DermCom can thus rejuvenate the skin matrix thanks


to its growth factor-like activity and so preserve and
­improve the biomechanical properties of the skin as
well as its quality.

DermCom is COSMOS approved *.

  * Raw material approved by ECOCERT GREENLIFE in accordance with the


COSMOS Standard September 2019
Skin Aging
Growth factors synthesis is reduced with age

Age Depletes the Communication Process between Cells The Reduced Synthesis of Natural Growth Factors
Fibroblasts, the major cells of the dermis are capable ­Affects the Skin’s Structural Network
of sending and receiving messages from other skin Due to the reduced release of growth factors, the activity
cells ­using growth factors and cytokines as messengers. of fibroblasts decreases; they synthesize less collagen
This dialogue is essential for skin regeneration, repair and elastin, the two major proteins which form the ECM,
and for growth of the tissues. Released by the cells, but generate more matrix metalloproteinases (MMP)
these messengers reach their target cells by diffusion which degrade the existing matrix. This leads to an
and bind them thanks to specific surface receptors. ­imbalance in the renewal of ECM since its degradation
surpasses its neosynthesis. This causes important alter-
With age, this communication process is reduced. This ations in the skin (loss in firmness, elasticity and density
strongly affects the extracellular matrix (ECM), the struc- resulting in skin sagging and thinning).
tural network which supports the skin and provides it
with its biomechanical properties (firmness, elasticity) Reaching Fibroblasts via Intercellular Communication
as well as its thickness and density. Dermal fibroblasts cannot be reached easily by topically
applied cosmetics. However, as these cells communicate
with the keratinocytes which are in the outer skin layers,
they could be reached using this communication process
– a new strategy for cosmetics.
DermCom
A flower bulb extract with a growth factor-like
­activity to repair the skin matrix
“Cream Beauty” Crocus Bulb, a New Source for DermCom Mimics the Activity of Natural Growth
­Cosmetics ­Factors in the Dermis
Bulbs are plant parts specializing in the storage of ­nutrients An active ingredient was developed from a Crocus
used to generate a new plant after a low-­temperature- ­chrysanthus bulb extract. DermCom, the resulting
induced dormancy period. product, was shown in a series of tests to stimulate
­keratinocytes to secrete growth factors that could
Crocus chrysanthus bulbs were selected from several bulb ­enhance the synthesis of matrix proteins in the dermis.
plants for their safety, availability and activity on the skin.
Its activity on fibroblasts was comparable to the one of
Crocus is actually a bulb-like plant; contrary to real bulbs the transforming growth factor (TGF-β) which activates
(e.g. tulips) that store nutrients in modified leaves, crocus the synthesis of ECM proteins (collagen and elastin).
is a corm meaning that it stores nutrients in the modified DermCom has thus a growth factor-like activity in the
stem. dermis.

As an early spring-flowering plant, Crocus chrysanthus


is a universal symbol of rejuvenation and youthfulness.
This species grows in the mountains of southern Europe.
Its attractive cultivar “Cream Beauty” owes its name
to its creamy yellow petals contrasting with its bright
­orange center.

Mechanism of DermCom

Stratum
corneum
Aging

Epidermis

DermCom

Dermis

Fibroblast Elastin fibers Collagen fibers Growth factors released by keratinocytes


Growth factors released by fibroblasts
DermCom
Study results

Effect on Epidermal – Dermal Cell-Cell


­Communication
The effect of DermCom on keratinocyte-fibro- Fibroblasts of a pool of donors over 50 years old
blast communication was evaluated using DNA micro-­ were treated or not with:
array technology and was compared to the TGF-β growth • the previously obtained secretions of the
factor one. untreated keratinocytes (control)
For this, gene array analysis was conducted on: • the previously obtained secretions of the
• keratinocytes and fibroblasts “directly” treated with DermCom-treated keratinocytes
DermCom • TGF-β (external positive control)
• fibroblasts “indirectly” treated with DermCom in order • DermCom (direct control).
to mimic the reality. For this, fibroblasts were incubated
with the secretions of keratinocytes treated first with At the end of the incubation, fibroblast cells were
DermCom. washed. The expression of matrix proteins in these
cells was analyzed by quantitative PCR.
Keratinocytes from a 50 year old donor were treated
or not with DermCom. The cell cultures were then
­centrifuged to separate the cell pellets from the super-
natant (keratinocyte secretions). Then, the keratinocyte
cells were washed and the expression of growth factors
typically expressed in these cells was analyzed by
­quantitative PCR.

Study Design

+/– Supernatant =
1 % DermCom keratinocyte secretions

Analysis
of gene expression

Keratinocyte culture Fibroblast culture

S-346 / © Mibelle Biochemistry


Growth Factor-Like Activity
Gene expression analysis conducted on fibro- The gene expression coding for the connective tissue
blasts incubated with the test products for 24 h growth factor (CTGF) was also analyzed in fibroblasts
showed that: ­after 24 h and 72 h of incubation with the different
• secretions of untreated keratinocytes (coming from a test products. CTGF stimulates the production of
50 year old donor) had a pro-aging effect on fibroblasts ­collagen by fi
­ broblasts and is significantly reduced
(control). This resulted in a reduced expression of elastin in aged skin.
and lysyl oxidase-like 2 (LOXL-2), an enzyme required
for elastic fiber formation. Secretions of untreated keratinocytes showed an aging
• DermCom, when applied directly to the fibroblasts, effect by significantly reducing CTGF expression.
had no effect or a slight pro-aging effect on these cells. ­However, here also, secretions of keratinocytes treated
• as expected, TGF-β had an anti-aging effect on fibro- with DermCom had a similar effect to TGF-β and led
blasts as it led to a strongly increased expression of to an i­ncreased expression of CTGF.
elastin and LOXL-2.
• secretions of keratinocytes treated with DermCom This indicates that the stimulatory effect of DermCom
had a strong anti-aging effect comparable to the on the synthesis of matrix proteins is due to the
TGF-β’s one. ­compounds secreted by the keratinocytes when they
are first treated with DermCom.

DermCom can thus reverse the aging process by


­stimulating the communication between keratinocytes
and fi
­ broblasts in aged skin.

Stimulation of Elastin Fiber Formation in Fibroblasts Stimulation of CTGF in Fibroblasts

1400 500
x 4.6
Gene expression after 24 h relative to control

x12
1200
Gene expression relative to control

400
1000

300
(=100) in %

(=100) in %

800

600
x 4.9 200

400
100
200

0 0
Elastin LOXL2 After 24 h After 72 h

S-346 / © Mibelle Biochemistry S-346 / © Mibelle Biochemistry


DermCom
Study results

Stimulation of Growth Factors Firming Effect after 2 Weeks of Treatment


Gene array analysis conducted on keratinocytes 20 women aged from 36 to 65 (average: 47.1)
showed that DermCom increased the expression applied a cream containing or not 2 % DermCom
of growth factors playing an important role in keratinocyte twice daily for 28 days to the inner side of their forearms.
growth, tissue repair and communication between the The firmness of their skin was determined using a cuto-­
­epidermis and the dermis: meter.
• fibroblast growth factor 5 (FGF-5)
• fibroblast growth factor 7 (FGF-7) Results showed that DermCom significantly increased
• connective tissue growth factor (CTGF) skin firmness:
• insulin-like growth factor binding protein 6 (ILGFBP6). • by more than 11 %** after 14 days
• by almost 13 %** after 28 days.
Thus, the anti-aging effect of DermCom relies on the **p<0.05 versus untreated and placebo
stimulation of the keratinocytes to release growth
­factors. And these growth factors are able to enhance DermCom offers thus a rapid firming effect to the skin.
the synthesis of matrix proteins in the dermis as shown
in the previous steps of the study.

Stimulation of Growth Factors in Keratinocytes Increase in Firmness

Placebo 2 % DermCom

300 15

**
Increase in skin firmness compared to
initial conditions and untreated in %

250
Gene expression relative to control

12
**

200
9
(=100) in %

*
150

6
100 *

3
50

0 0
FGF-5 FGF-7 CTGF ILGFBP6 After 14 days After 28 days
*p<0.05 versus untreated
**p<0.05 versus untreated and placebo

S-358 / © Mibelle Biochemistry S-352 / © Mibelle Biochemistry


Matrix’ Rejuvenation after 2 Weeks of
­Treatment
A cream containing 0.4 % DermCom was applied Collagen and elastin were visualized before and after
twice daily to the inner side of the forearm of a 53 year 2 weeks of treatment and their content was measured
old woman whilst her other forearm was treated with the in the papillary dermis and in the upper part of the
corresponding placebo. ­reticular dermis.

Analysis of skin matrix was performed using a two-­ Results showed, already after two weeks’ treatment,
photon microscopy. This innovative non-invasive 3D that DermCom increased the content of the two main
technique visualizes deeper skin structures. It is based skin structure components compared to the placebo:
on the principle that infrared laser irradiation can • by more than 115 %** for collagen
cause autofluorescence of some molecules (e.g. elastin) • by more than 25 %*** for elastin.
or second harmonic generation (e.g. collagen). **p<0.001, ***p<0.01

Increase in Collagen and Elastin Contents

Placebo 0.4 % DermCom


Dermal Epidermal Junction Dermis
120
*
**
to initial conditions after 2 weeks in %
Increase in protein content compared

100

Placebo
80

60

40
***
20
0.4 %
DermCom 0

-20
Collagen Elastin
* p<0.05 versus initial conditions
*** p<0.01 versus placebo
Collagen Elastin ** p<0.001 versus placebo

S-374 / © Mibelle Biochemistry S-374 / © Mibelle Biochemistry


DermCom
Study results

Reduction of Stretch Marks


Striae distensae, which are more commonly The clinical placebo-controlled study to prove this activity
known as stretch marks, arise from the progres- was conducted on eighteen Caucasian women aged
sive stretching of the skin during pregnancy or following ­between 18 and 50 years with striae (thighs, abdomen
weight gain. The marks appear vertical to the direction or breasts) and left and right symmetric distribution
of the greatest tension indicating a rupture of the con- of equivalent striae.
nective tissue.
The areas affected by stretch marks were treated twice
Stretch marks undergo an evolution from an initial daily for 56 days by applying a cream with 2 % DermCom
­inflammatory phase (striae rubra) to a later chronic phase on the stretch marks covering one half of the volunteer’s
(striae alba). In comparison to the normal surrounding body. Meanwhile, the respective placebo was applied
skin, the skin in areas where stretch marks are present is to the stretch marks on the other half of the body.
characterized by thinning as a result of a loss of the
main matrix components – collagen and elastin – and Results showed a significant decrease of 10 % in skin
the flattening of rete ridges in the underlying papillary redness following 56 days of treatment. Skin lightness
dermis. L* was increased by∆1.2 units (∆L* of 0.3 units is visible,
data not shown).
In previous studies, DermCom was shown to stimulate
keratinocytes to release growth factors that enhance the Therefore, DermCom is an efficient active for the treat-
synthesis of matrix proteins in the dermis. Furthermore, ment of stretch marks on all parts of the body.
DermCom was proven to increase the content of the
two main skin structure components in vivo (115 % for
collagen and 25 % for elastin). Consequently, DermCom
could be used in the treatment of stretch marks.

Reduction of Redness in Stretch Mark Skin Reduction of Stretch Marks

Placebo 2 % DermCom Before After

0
Decrease in skin redness compared
to initial conditions in %

-2

-4

-6

-8

-10
*

-12
Day 28 Day 56
* p<0.003 versus t0

S-470 / © Mibelle Biochemistry S-470 / © Mibelle Biochemistry


Perception of the Efficacy by Self-Evaluation Visible Anti-Wrinkle Effect
The effects of DermCom were evaluated by 11 women aged from 40 to 57 (average: 48.3)
42 women aged from 50 to 60 (average: 57) applied a cream containing 2 % DermCom
with ptosis. twice daily for 28 days. Macrophotographs were taken
The volunteers were separated into 2 groups. before and after the treatment.
• To the faces of one group, a 2 % DermCom emulsion
was applied twice daily for 56 days. Analysis of the pictures of the volunteers treated with
• The same treatment was carried out on the second the 2 % DermCom emulsion showed a visible reduction
group using the corresponding placebo. of the depth of wrinkles on the crow’s feet area com-
At the end of the study, the volunteers were pared to initial conditions.
asked, using a questionnaire, to tell whether they
­perceived improvements of specific criteria.

Results showed a clear difference between the volunteers


who used the 2 % DermCom emulsion compared to
the ones who used the corresponding placebo regarding
the elastic properties and appearance of their skin:
• 71 % of the volunteers who used DermCom
found their skin firmer
• 67 % found their skin toned
• 67 % found that their skin looked younger.

Perception of the Firming Effect Visible Anti-Wrinkle Effect

Placebo 2 % DermCom

Redensified**
80

60

40
Looks
younger** Firmer***
20 Before

Replumped* Toned***

* p=0.03 versus placebo


** p=0.013 versus placebo After 28 days
*** p<0.006 versus placebo

S-373 / © Mibelle Biochemistry S-443 / © Mibelle Biochemistry


DermCom
Cell2cell communication
Mibelle AG Biochemistry, 5033 Buchs  /  Switzerland, Phone + 41  62 836 17 31, info@mibellebiochemistry.com, www.mibellebiochemistry.com

for skin matrix repair

DermCom
• Boosts collagen and elastin production
• Stimulates natural growth factors of the skin
• Renews the skin’s resilience and firmness
• Reverses aging processes
• Rejuvenates skin texture
• Visibly reduces stretch marks

Applications
• Collagen and elastin boosters
• Firming and lifting products
• Repair formulas
• Stretch mark creams
• Intense anti-aging treatments

Marketing Benefits
ON
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• Four time awarded active ingredient:
RS

Silver Award at Innovation Zone Best Ingredient Award in-cosmetics Europe


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Silver Award at Innovation Zone Best Ingredient Award in-cosmetics Asia


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Silver Award at BSB Innovation Prize
Gold Award at CPCIA Personal Care Ingredients
• Based on a flower bulb, an interesting source for cosmetics
• An advanced strategy to successfully rejuvenate the skin matrix deep in the dermis
• COSMOS approved

Innovating for your success


Mibelle Biochemistry designs and develops innovative, high-quality actives based on
naturally derived compounds and profound scientific know-how. Inspired by nature –
Realized by science.

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. Any
statements are offered solely for your consideration, investigation and verification and do not relieve you from
your obligation to comply with all applicable laws and regulations and to observe all third party intellectual prop-
erty rights. Mibelle AG Biochemistry will not assume any expressed or implied liability in connection with any use
of this information and disclaims any and all liability in connection with your product or its use. No part of this
publication may be reproduced in any manner without the prior written permission of Mibelle AG Biochemistry.

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