Development of natural actives for Spa and cosmetic products€¦ · rosavin salidroside Rhodiola...
Transcript of Development of natural actives for Spa and cosmetic products€¦ · rosavin salidroside Rhodiola...
Chia Wen ChenChia Wen Chen
Director of Natural ProductsDirector of Natural Products
Estee Lauder CompaniesEstee Lauder Companies
September 24, 2009September 24, 2009
SCC Education DaySCC Education Day
““Development of Development of
NaturalNatural Actives for Actives for
Spa and Cosmetic Spa and Cosmetic
ProductsProducts””
R&D Capabilities
Product development assistance (scale up from a bench top process)
Phytochemical analysis (to determine marker compound)
Full analytical support (method development)
Requirements
ISO 9001:2000 certified (cGMP)
Heavy Metal and Pesticide analysis
Safety test for topical application
Sustainable Biomass (wild craft, cultivation)
Certified Organic (NOP, EcoCert, IFOAM)
Lot to lot consistency: What are we really getting?
Microbial issues 10,000 cfu for dietary supplement vs 100 cfufor cosmetic
Heavy metal and Pesticide analysis – due to the pollution in soil and water
Regulatory (REACH) and Safety (Topical)
Patents- not patent protected
Converting an ingestible for topical use (need to define biological activity)
Challenges
Cosmetic Products
Are designed not only to moisturize the skin
and reduce the visibility of lines and
wrinkles…
But also to protect the skin from the
damages caused by environmental exposure.
TCTC
EC
FB
TC
MN
KC
UV
ILIL--11ααααααααPLAPLA22
TNFTNF
MMPMMP--11
PLAPLA2 2
Nitric oxide (NO)
Blood flow
Pain Irritant Allergen
NO
NO
AA PGE2
PL AA
PLA2
COX2
ILIL--11αα
PMN
IL-12
Collagenases
PG’sCAMs
UVB, ozone, smoke
PL
A2arachadonic acid
PGE2
cox2
neutrophil
vasodilation
macrophage
collagenaseelastase
UVBO3
O3
O3
Ozone
cigarette smoke
Dermiscapillary
collagen
Basement membraneEpidermis
O3
PGE2PGE2
neutrophil
Control of Inflammatory Reactions
Must take place at the very beginning of the cascade of reactions.
Inhibition of Phospholipase A2 will result in the control of the release of Arachidonic Acid, a major inflammatory mediator.
Additional anti-inflammatories will subsequently modulate the other steps of the cascade.
Insult (UV exposure, oxidative stress)
Activation of Phospholipase A2
Release of Arachidonic acid
Cyclo-oxygenase
Release of
Prostaglandins
Lipoxygenase
Release of LeukotrienesCytokines
(ILI,TNF ∝)
Recruitment of Leukocyte cells
Transport of Leukocytes by blood
Transfer to site of injury (chemotaxis)
Second oxidative burst and Protease (collagenase, elastase, tryptase)
Premature Aging
Poria Cocos
CentauriumResveratrol, hops
Rosemary, Citri reticulatae peel Grape seed extract
The Trend Toward Natural
Your consumers are watching and learning!
Consumer awareness is at an all time high.
Consumers want healthy products - and the industry is responding.
Natural ingredients and healthy lifestyle are attractive to consumers.
Morus spp.
Over 80% of the world's population uses plants as their primary medicines
500,000 plant
species
10,000substances per species
What makes plants so efficacious?
multi-taskers
� inpired by many years of folklore
� validated by science
� biodegradable and sustainable
;
High performance ingredientsFor high performance skin care
Finding new ingredients
Partnership with consultants and suppliers all over the world
Strategic alliance with academic research
OH
O
HO
OH O
OHO
HOOH
O
O
OH
O
HO OH OH
HO
rosavin salidroside
Rhodiola rosea
Treatment of skin cells with Rhodiola extract enhanced the ability of
the cells to survive after exposure to an external stress
(UV exposure)
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UVB dose (mJ/cm2)
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Rhodiola rosea
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UVB dose (mJ/cm2)
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Rhodiola rosea
After 24 hours the number of damaged cells was
more then 2X lower in the Rhodiola treated skin model
Rhodiola rosea Enhances Rebound from Stress
ATP (energy depletion)
Mitochondrial DNA damageDNA damage
Cellular Damage (UVB, oxidative damage, inflammatory cytokines)
(-)Physiological effects
cancer
Animation 2
Animation 4
vs.
TREATED with Rhodiola rosea
Dark brown staining identifies heavily damaged skin cells. The
removal of damage was much faster in Rhodiola treated tissue.
Skin model stressed by simulated UVNo treatment
Rhodiola rosea Enhances Rebound from Stress
Mimosa tenuiflora
Mimosa bark extract with Flavonoids, tannins and saponins.
Anti-collagenase: EC50 = 80 ug/ml
Collagen synthesis: 31% at 0.0625 µg/ml and by 67% at 0.25 µg/ml,
Anti-collagenase Activity of Tepescohuite
EC50 = 80ug/ml
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[tepescohuite] µg/ml
% i
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Collagen Assay: Tepescohuite
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Media 0.015625 0.0625 0.25
Dose (µg/ml)
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Stratum
corneum
Langerhans
cell
melanocyteMast
cell
elastosis
collagen
elastin
Young skin Old skinPhotodamaged skin
Loss of collagen & elastin
Degraded collagen, thickened elastin
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Fragmented Fibrils
vs. Young cells Old cells
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In vitro cell proliferation as a function of age
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ng
)In vitro collagen production as a function of age
What makes a wrinkle
Stress induces damages to skin cells result in further loss of skin integrity – Wrinkle formation
Constant folding & unfolding of skin creates a weak point: the micro-tear.
Physical pressure on cells activates inflammatory reactions lead to premature degradation of collagen by collagenase
Wrinkle animation (4) skin folding Wrinkle animation (4) skin folding
development of inflammatory development of inflammatory
reactionreaction
Anti-Age: Dermatological Approach
Skin’s repair process activated by damaged skin cells. BENEFIT: improves skin
Inflammatory reaction degrades collagen & elastin. SIDE EFFECT: ages skin
Peels and lasers trigger cell’s natural defense mechanism.
Prevent : control collagenase, elastase and GAGasedegrading enzyme to prevent wrinkle formation.
Restore: collagen synthesis to accelerate “Healing” of skin
Repair:
help skin cells rebound from stress and prevent premature aging
Anti-Age: A Natural Approach
Healthy skin Aging/stressed skin
Collagen
Collagenase
Endogenous collagenase inhibitors
Collagen Fragmentation by Collagenase
ANIMATION 5b ANIMATION 5b collagenasecollagenase inhibitorinhibitor
ANIMATION 3 treatment of whole skin; fragments go to ANIMATION 3 treatment of whole skin; fragments go to
fibroblasts, activate collagen production. fibroblasts, activate collagen production.
Anti-Age: Wrinkle
Prevent premature destruction of key dermal components
Treatment:Anti-collagenase (Sigesbeckia, Tepescohuite)Anti-elastase (Boswellia, White Birch)Anti-GAGase (Silymarin, Centaurium)Collagen synthesis (Tepescohuite)
Result:Treatment of skin, most damaged by constant folding / unfolding.
Matricaria recutita flower
German Chamomile
Blue chamomile oil with confirmed:
5-LO inhibitory activity: EC50 = 50 ug/ml
Anti-chemotaxis: 97% inh. At 0.05%
LPO: EC50 = 0.003%
5-Lipoxygenase assaySCOPE
To analyse potential inhibitors of potato 5-lipoxygenase (5-LO).PRINCIPLE
5-lipoxygenase converts the substrate linoleic acid (diene 1-4) to a conjugated dieneproduct (diene 1-3), which can be detected at 234nm. A decrease in the absorbancesignal is indicative for an increased anti-5LO activity.
MATERIALNormal lab equipment
96 well half area plates with UV transparent bottom (Costar, 3679)8 channel multi pipette (20-200µl)
SpectrophotometerREAGENTS
H2O distilledPotassium dihydrogen phosphate (Acros, #205925000)
Dimethylsulfoxide (Acros, #12779)Potato 5-lipoxygenase (Cayman, #60400)
Linoleic acid 99% (Acros, #215040050)Nordihydroguaiaretic acid from Larrea divaricata (creosote bush) (approx. 95%)(reference inhibitor - NDGA) (Sigma, N1144)
Tween-20 (Janssen Chimica, #2333656)
5-Lipoxygenase Inhibition
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[Blue chamomile oil organic (Hashem Brothers, #4905)] (µg/ml)
% Initial 5LO activity
IC50 ~50µg/ml
Chemotaxis Assay: Blue Chamomile Oil Organic
(BRD 4905)
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PM
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97% inhibition at 0.05%
LPO (Anti-oxidant)
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0.001
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0.002
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30 min 120min
Conclusions
The development of new ingredients from plant
extracts involves many steps which can ultimately provide great benefits in cosmetics.
Despite the cost involved in such development, we believe that active ingredients from natural
sources provides the cosmetic industry with a quasi infinite source of ingredients which we are aiming at developing in the future.
Conclusion
Opportunity not a Headache
Carefully choose your partner
Know what you are working with
(Standardize extract)