Sytenol®A
Acne-affected Skin
Sytenol®A for the Management of Acne-affected Skin
Acne is a common, chronic, and recurring disease. Acne involves multiple etiological factors including follicular
hyperkeratinization, increased sebum production, Propionibacterium acne proliferation, and inflammation [Leyden, J Am Acad
Dermatol 32 S15–S25,1995]. Acne affects about 80% of teenagers and young adults. Acne usually becomes less of a problem after
the age of 25 years. The cause of acne is due to the higher levels of sex hormones, especially the androgens (such as testosterone),
at puberty than in younger children. Testosterone is converted in the skin to dihydrotestosterone (DHT) by a-reductase which
stimulates oil glands to enlarge. The oil glands (sebaceous glands) produce sebum. The more sebum, the more likely it is that acne
will be troublesome. If sebum and keratin block the skin pores, comedones can develop. The wall of the follicles may rupture.
Bacterial and comedonal debris cause acne pimples or pustules (inflammatory lesions). Typical acne appears in the oil-producing
areas of the body, namely, the face, chest, and back.
Product Information
Trade Name
Sytenol® A
INCI Name
Bakuchiol
CAS #
10309-37-2
ELINCS
N/A
Harmonized Tariff #
29071190
Appearance
Yellow viscous liquid
Assay (GC)
95% (w/w) min Bakuchiol content
Solubility
Highly miscible with a wide range of hydrophobic emmolients and solubilizers
Suggested use level
0.5 to 1%
Storage
Store in original, sealed container at +10 to +30 0C; Avoid light & heat
Patent status
Covered by multiple US and world-wide patents
Safety Data:
REACH-ready safety profile available upon request
q
q
q
q
q
No skin irritation & No skin sensitization (HRIPT) at 2 and 5% dilution in corn oil
No eye irritation (In-vitro; alternate to Draize methodology)
Non-genotoxic in the in-vitro micronucleus assay in human lymphocytes
Non-mutagenic based on TA98 in Salmonella typhimurium Reverse Mutation Assay
Passes aquatic toxicity tests (short-term, Zebra fish & Daphnia magna); Fresh water single cell green alga & biodegradability
Regulatory Status:
USA:
Allowed for personal care applications
Europe:
Up to 1 Ton annual use requires no REACH registration
Rest of the World:
Allowed for use in most Asian, South American and African countries
Consult your regulatory authority for any restrictions this product may have for
use in your country
Stages of the Development of Acne
0 - Normal skin 1 – Whiteheads 2 – Blackheads 3 – Pustules & Nodules 4 - Cysts
What are the Treatment Options Available for Acne?
There are four major principles presently governing the therapy of acne:
q
q
q
q
Correction of the altered pattern of follicular keratinization
Decrease sebaceous gland activity (5-α-reductase inhibitor)
Decrease the follicular bacterial population (especially P. acne)
Produce an anti-inflammatory effect
At present, oral or topical isotretinoin (retinoic acid) is the only single agent which is effective against all four major pathophysiologic
features. However, it is responsible for several side effects such as skin irritation, skin sensitization, phototoxcity and teratogenicity.
Most common alternate approaches include exfoliating agents, such as, salicylic acid, glycolic acid. Skin becomes more sensitive to
sun-induced damage when exfoliating agents are used for a long period of time. Benzoyl peroxide is another very common agent
found in anti-acne products. However, in the US, benzoyl peroxide is now a category III ingredient pending further studies whether
UV-radiation enhances development of skin cancer. The recommendation now is that acne treatments should be combined to target
as many pathogenic factors as possible [KurokawaIet al., Exp Dermatol, 18(10):821-832, 2009]. Sytenol® A in combination with
salicylic acid can provide a solution to acne-affected skin.
Acne-affected skin has been shown to have many other problems:
q
Presence of high levels of Staphyloccus and Candida
q
Impaired antioxidant defense system
q
Presence of high levels of matrix-degrading metalloprotease
Sytenol® A Down-regulates 5-α-reductase Expression
Cells: HaCaT human kerationocytes; At confluence,
cells were trypsinized and seeded in micro plates
at a density of 50,000 cells per well
Incubation time: 48 hours of incubation at 37°C in
an atmosphere containing 5% CO2; Supernatants
discarded and the cells washed using sterile PBS.
Estimation of 5-α-reductase expression:
Immunofluorescence
technique
using
specific
antibody;
Determined
spectrofluorimetrically
at wavelengths 485 nm (excitation) and 518 nm
(emission).
Result:
At 10 µg/ml, Sytenol® A and Retinoic acid downregulates 5-a-reductase expression by about 40%.
% Down-regulation
of 5-a-reductase expression
Sytenol® A has Broad Antibacterial & Antifungal Activities
Using a genetically based strategy with sensitivity and a discriminatory power surpassing those of culture-based
methods, Bek-Thomsen et al has demonstrated recently that the follicles from healthy skin were exclusively colonized by
P. acne, whereas the follicular microbiota of acne patients included, in addition, Staphylococcus epidermidis and minor
proportions of other species [Bek-Thompson et al., J Clin Microbiol, 46(10):3355–3360, 2008]. A recent clinical study has
shown that Retinol and Retinoic acid do not have any antibacterial activity whereas Retinal is a very effective inhibitor of
Staphylococcus and Candida [Slobododnikova et al., Phytother Res, 18(8):674-676, 2004].
Sytenol®A minimun inhibitery concentration (µg/ml)
Microorganisms
Sytenol® A
Retinol
Salicylic acid
P. acne
1.5
1
2
1.5
31
N/D
>100
Staphylococcus aureus
Staphylococcus epidermidis
Candida albicans
N/D
N/D
N/D
N/D
N/D
Sytenol® A Relieves Inflammation by Down-regulating Pro-inflammatory
Genes and Enzymes
Pro-inflammatory gene expression
Cyclooxygenase-1 (Prostaglandin G/H synthase precursor)(PTGS1/
COX-1): Prostaglandin biosynthesis; Acts both as a dioxygenase and
as a peroxidase
Phospholipase A-2-activating protein (PLAA): Eicosanoid synthesis,
release of neutrophil lysosomal enzymes and superoxide and on RBC
hemolysis
Cytosolic phopholipase A2 (PLA2G4A): Catalyzes hydrolysis of
membrane phospholipids to release arachidonic acid which is
subsequently metabolized into eicosanoids
Prostaglandin E2 receptor EP2 subtype (PTGER2): Inflammatory
reaction via the EP2 receptor through its regulation of TNF-alpha and
IL-6 Prostaglandin E2 receptor EP4 subtype (PTGER4): Inflammatory
reaction via the EP4 receptor through its regulation of TNF-alpha and
IL-6
Prostaglandin dehydrogenase 1(HPGD):
Degrades PGF2a and
PGE2 (cause inflammation) and converts to hydroxy metabolites
(anti-inflammatory)
Fold change vs Control
Sytenol® A is an excellent inhibitor of pro-inflammatory enzymes: Phospholipase A2, iNOS and COX-2
Sytenol® A Improves Compromised Antioxidant Defense System
A recent clinical study has confirmed the role of reactive oxygen species in inflammation of acne by
determining the activity of antioxidant defense enzymes in leukocytes [Basak et al., J Dermatol, 28(3):123127, 2001]. Oxidative breakdown of squalene and other skin lipids may not merely be a consequence of the
acne process, it was suggested by AL Lorincz in 1965 that lipid peroxides might be directly acnegenic to the
skin [Lorincz, Armed Services Technical Information Report, AD467008:1-12, 1965]. This has been proven
clinically [Bowe et el., Lipids in Health and Disease, 9:141-151, 2011]. Squalene was shown to be highly
sensitive to oxidation and researchers reported that both squalene and its oxidized metabolites are found at much
higher levels in acne vs. healthy controls.
Sytenol® A is a Broad-Spectrum Antioxidant
Sytenol® A Up-regulates Antioxidant Defence Genes
Antioxidant Defense Gene Expression
Glutathione
glutathione
peroxidase
3
peroxidase(GPX3):
precursor/
Protect
Extracellular
organism
from
oxidative damage. Reduce lipid hydroperoxides --> alcohols
and hydrogen peroxide --> water
Glutathione S-transferase theta -1 (GSTT1): Involved in the
detoxification of endogenous compounds, such as peroxidised
lipids, as well as the metabolism of xenobiotics
Glutathione S-transferase P 1(GSTP1): Same as above
NAD(P)H dehydrogenase [quinone] (NQO1):This protein’s
enzymatic activity prevents the one electron reduction of
quinones that results in the production of radical species.
Fold Change vs Control
Sytenol® A Provides Skin Relief by Inhibiting Matrix Metalloprotease
Enzymes & Genes
Matrix metalloprotease (MMP) level in acne-affected skin is much higher than in normal skin
[Papakonstantinou et al., J Invest Dermatol, 125(4):673-684, 2005]. MMPs have been reported to have a
predominant role in inflammatory matrix remodeling and hyper-proliferative skin disorders. MMPs also
cause destruction of extracellular matrix proteins, like, collagen, fibronectin, laminin, elastin. Diminishing
the presence of matrix-degrading enzymes in the acne lesion reduces imperfect repair of the skin and thus
decreases scarring in acne-affected skin.
Sytenol®A inhibits matrix degrading (MMP) enzymes
Matrix Metalloprotease
Method Used
Sytenol®A
Retinol
MMP-1 (Collagenase)
Enzcheck collagenase assay kit
(Molecular Probe)
Calbiochem human neutrophile
elastase kit (Cat # 324681)
50% inhibition at 1 mg/ml
Not determined
70% inhibition at 1 µg/ml
8% inhibition at 1 µg/ml
MMP-12 (Elastase)
Sytenol®A up-regulates Elastase-specific inhibitory genes
Gene
Gene Description
Function
Fold Change Vs. Control
Sytenol® A Retinol
PI3
Elastase-specific inhibitor
SERPINB1
Leukocyte elastase inhibitor
Suppresses degradation of connective tissue
components, such as elastin, and collagen.
Suppresses the development of solar elastosis
and skin tumors
+2.7
+2.5
+6.1
+3.8
Human Clinical Studies
% Reduction in Acne
weeks
6
Protocol 1
n Number of subjects – 4x15
n Duration – Six weeks
4
n Application frequency – Twice/day
n Method of evaluation – Global acne
2
grading system [Burke & Cunliffe, The
assessment of acne vulgaris, British J
Dermatol, 111:83-92, 1984]
score
Results
Sytenol®A is clinically proven to work with salicylic acid in improving the condition of acne-affected
skin. In a six-week study, a 67% reduction in acne lesson observed with a lotion containing 1%
Sytenol®A and 2% Salicylic acid
!
!
Woman 1
Protocol 2
n Number of subjects – 10
n Formulation – 1% Sytenol®A lotion
Before n Duration – Six weeks
After 6 weeks
n Application frequency – Twice/day
Method of evaluation – Global acne
grading system & photography (Visia CR)
n
!
Woman 2
!
Results
Before
After 6 weeks
Sytenol®A is clinically proven to work in
improving the condition of acne-affected skin.
In a six-week study, a significant reduction in
acne lesson with overall improvement of skin
appearance was observed with a lotion
containing 1% Sytenol®A.
Sytenol®A provides significant improvement in acne-affected skin
It works by:
q
Down-regulating 5-α-reductase expression
q
Inhibiting P. acne and other bacteria & fungi
q
Down-regulating/Inhibiting pro-inflammatory genes/enzymes
q
Quenching radicals and non-radicals and by up-regulating antioxidant defense genes
q
Inhibiting/down-regulating matrx metalloprotease enzymes/genes
Sytenol®A has an excellent safety profile, easy to formulate, is non-skin irritant and
non skin sensitizer based on human repeat insult patch test and has no photo-or
hydrolytic- stability issues and thus can be used throughout the day. Topical formulations
that include Sytenol®A are likely to lead further improvements in the way we treat skin
infected by acne and beyond.
USA:
315 Wootton Street, Boonton, NJ 07005
www.sytheonltd.com - [email protected]
Disclaimer
The information given and the recommendations made herein are based on our research and literature search
and are believed to be accurate but no guarantee of their accuracy is made. This information is intended to
be helpful, but no warranty is expressed or implied as to the results obtained from use in the formulation,
procedure or products suggested herein. Neither is any permission or recommendation to practice any
invention covered by patent either expressed or implied.
Tel.: +1 973.988.1075
FRANCE:
1ère avenue, 1ère rue, BP 383 06514 Carros Cedex
www.sytheonltd.com - [email protected]
2011 - www.growitgroup.com
Tel.: +33 (0)4.92.08.52.42