(Microsoft PowerPoint - COSMELAN POLONIA [S\363lo lectura])

COSMELAN 1 & 2
Depigmenting Topical Treatment
Dr. F. Garcí
García
April 2007
Scheme of Presentation
I.
Melanins Metabolism
II. Skin Melanics Abnormalities
III. Topical Depigmenting Strategies
IV. Cosmelan 1 & 2
V. Application Protocol
VI. Results
I. Melanins Metabolism
A. Melanogenesis
•Melanocytes:
Melanocytes
–Epidermal dendritics cells set up in the basal epidermis adjacent to
keratinocytes and Langhergans cells. The melanocytes are producing
melanins by means of specific subcellular intracitoplasmatic
structures named melanosomes, the real factories of melanines.
•Melanodermic Functional Unity:
–A functional set constituted by one melanocyte plus 30 or 40 near
keratinocytes.
–Through the dendritics branches of the melanocyte, the melosomes
containing melanins are injected into keratinocytes the melanosomes
containing melanins.
I. Melanins Metabolism
A. Melanogenesis
Cellular Epidermal Kinetics:
The keratinocytes show a process of proliferation and differenciation very
well regulated which lead its transformation into a corneocytes.
The Melanosomes injected into the keratinocytes, release the melanins
inside them and remain there till its transformation into cormeocytes.
At the end of this kinetic cellular process, the corneocytes containing
keratine and melanins appear conjointly with ceramides and other lipids,
forming the stratum corneum of the epidermis.
In this way, the corneocytes containing melanins work as a skin
protector cloak in the outer part of skin
Melanogenesis
I. Melanins Metabolism
A. Melanogenesis – Melanins Biosynthesis
Common metabolic pathway:
• The key step is the oxidation of tyrosine by the enzyme tyrosinase,
to produce dihydroxyphenylalanine (DOPA).
• The second one is the oxidation of DOPA to dopaquinone by
tyrosinase.
• Subsequently, dopaquinone is converted to dopachrome through
auto-oxidation process.
Eumelanins metabolic pathway:
• Dopachrome is enzymatically (dopachrome tautomerase & DHICA
oxidase) transformed into dihydroxyndole (DHI) or dihydroxyndole2-carboxylic acid (DHICA).
• Through complex polymerization reactions above intermediate
product, are converted in eumelanins.
I. Melanins Metabolism
A. Melanogenesis – Melanins Biosynthesis
Feomelanins metabolic pathway:
• Dopaquinone, in presence of cysteine or glutatione, is converted to
cysteinyl DOPA or glutatione DOPA
• Through complex polymerization reactions above intermediate
product, are converted in feomelanins.
I. Melanins Metabolism
B. Melanogenesis – Melanins Functions
• Skin photoprotection. They are the main responsables of the skin,
eyes and hair colour.
• Are strong absorber of UV radiation and, less, of the visible light of
the spectra.
• Work as stable free radical, neutralizing ROS.
• Inhibit the lipidic peroxidation of the cells membranes.
• Protect the skin against photoaging and photocarcinogenesis.
• Protect cellular DNA from actinic injuries.
• They have high chemically stability.
I. Melanins Metabolism
C. Melanogenesis – Melanins Types
•
Feomelanins:
Feomelanins
Yellow and reddish biopolymers containing high amount of sulfur. They give
the skin pigmentation to white and redhead people.
Scarce photoprotection capability.
Unlike eumelanins, they solve in alkaline solutions. By intensive UV
radiation, suffer decomposition forming free radicals.
•
Eumelanins:
Eumelanins
Black and brown biopolymers without sulfur. They have high amount of
nitrogen.
They have an excellent photoprotection capability, and chemical stability.
What amount of melanins exist in the skin?
– Fitzpatrick I < 1% (They suffer sun burn easily, high skin cancer risk)
– Fitzpatrick II y III: Between 1 & 3%
– Fitzpatrick IV > 3% (They do not suffer sun burn, low skin cancer risk)
I. Melanins Metabolism
D. Melanogenesis – Regulation
• The main and stronger factor to produce melanins is the UV radiation
(UV-A, UV-B), and less visible light.
• This answer is a protective mechanism of the skin.
• Another indirect stimulus are DNA fragment produced by the injuries of
UV radiation.
• The melanogenesis regulation is an local, complex and little known
mechanism related to endocrine, paracrine and autocrine process
through the action of several citokines between keratinocytes and
melanocytes.
• One hormone involved in the regulation process is alpha-MSH produced
non only in the hypophisis but also is produced in skin cells
(autocrine&paracrine regulation).
I. Melanins Metabolism
E. Melanogenesis – Elimination
• The physiological way for eliminating the human skin melanins is the
natural exfoliation process of the corneocytes from the stratum
corneum.
• This process is depending on the speed of proliferation and maduration
of the epidermal keratinocytes.
• Everyday a part of the corneocytes of the stratum corneum is lost and
with them their amount of melanins. These lost corneocytes are
replaced with new ones.
• The rapidity of this process, may be accelerated or braking for several
internal and external stimulus.
• An alternative way to eliminate melanins consists in the work of
macrophagic cells (monocytes), basically to eliminate the abnomal
location of melanins in dermal areas.
UV
MELANOCITOS &
GRÁNULOS MELANINA
MELANOSOMAS
L-TIROSINA
(fenilalanina)
TIROSINASA
(Cu2+, Fe3+, Zn2+)
DOPA
(3-4-dihidroxifenilalanina)
AM
TIROSINASA
(Cu2+, Fe3+, Zn2+)
a_melan
AGENTES
DESPIGMENTANTES
WHITENING
GLUTATION o CISTEINA
DOPA QUINONA
Ácido Ascórbico
LEUCODOPACROMO
Cisteinil - DOPA
Ácido Ascórbico
DOPA CROMO
DHI
5-6-Dihidroxi Indol
TPR2 ó
Tirosinasa Protein-2 Related
ó Dopa cromo-tautomerasa
DHICA
Ácido 5-6-Dihidroxiindol-2-carboxílico
1 - 4 - Benzotiazinilalanina
TPR-1 ó
Tirosinasa Protein-1 Related
ó DHICA
INDOL-5,6-QUINONA
DHICA
ÁCIDO INDOL-5-6-QUINONA
CARBOXÍLICO
DHI - MELANINAS
DHICA - MELANINAS
EUMELANINAS
Pigmento negro o marrón oscuroalcali
insoluble
FEOMELANINAS
Pigmento amarillo- marrón
Alcalisolubles (pelirrojos)
II. Skin Melanic Abnormalities: hyperpigmentation
•
•
Hyperpigmentation is the increase of the natural colour of the skin.
Darkened spots on the skin, have two main causes non acquired and
acquired:
– Non acquired:
• Related with genetic or hereditary predisposition.
– Acquired:
• Several factors promote melanogenesis in a localizated shape,
leading to appearance of melanic spots in the epidermis
and/or dermis, with more intensity and frequency in skin areas
sun exposed (face, neck and hands), or stressed by
enviromental factors.
• The spots are produced by:
– Excesive melanins prodution by melanocytes in a located
shape.
– Hypertrophy of located melanocytes which leads to more
melanin production.
II. Skin Melanic Abnormalities: hyperpigmentation
Classification
A. Melanocytes hyperactivity:
a. Melasma and cloasma: frequently in skin phototype I, II & III. Located
change of melanocytes producing feomelanins to produce amounts of
eumelanins due to sun injuries.
b. Freckles: normal melanocytes producing a big amount of melanins.
They are stimulated by the sun radiation. Appear in clear skins.
B. Melanocytes hyperproliferation:
a. Lentiges (actinic)
b. Lentiges (aging)
C. Phototoxicity: due to interaction of sun radiation with the skin plus
furocumarins.
D. Post-inflamatory process: produced by mechanical, physical or chemical
injuries on the skin which evoke an inflamatory state after leading a skin
hyperpigmentation (acne, laser, wounds, etc.)
II. Skin Melanic Abnormalities: hyperpigmentation
Diagnostic
•
Determining the cause of hyperpigmentation is important in
selecting the best approach for treatment. Based on the history and
the clinical findings of the patient, the etiology of the
hyperpigmentation
may
include
postinflammatory
hyperpigmentation, drugs, photosensitizing agents, UV light,
pregnancy, skin aging, acne, peeling, laser, photoageing, etc.
•
Skin exam under Wood Light
II. Skin Melanic Abnormalities: hyperpigmentation
Diagnostic – Wood Lamp
•
•
Emits UV radiation near to the maximum absortion of melanins.
Based on the quenching effect, the spots may be classified
according to its localization:
– Epidermal location: has a good contrast and are very well
detectable. They answer well and fast with topical
depigmenting agents.
– Dermal location: the contrast is lower. It answers slowly with
topical depigmenting agents.
– Mixed: shows spots located in epidermis and dermis.
– Nonvisible: characteristic in skin photo type V, VI. It is not
detected with Wood Lamp.
III. Topical Depigmentation Strategies
•
•
The skin application of depigmentant substances have the objective of:
– Eliminate the darkened spots
– Skin clarifying
– Skin embellishment
Mechanisms of depigmentation:
– All depigmentant substances work inhibiting the enzymatic process
involve in the melanogenesis. The key enzyme is tyrosinase, responsible
of the first part of melanins biosynthesis. Besides the inhibition of the
other oxidases enzymes increases the depigmentant action. The
enzymatic inhibition is reversible, that means, works meanwhile the
depigmenting agents are applied on the skin.
– The target of the depigmenting substances is the melanosomes.
– The lightening agents do not operate on the melanins spots. Its
elimination depending on the natural mechanism of melanins clearance
(skin exfoliation, phagocytosis by macrophages & skin cells).
III. Topical Depigmentation Strategies
•
•
•
•
•
•
This special mechanism implies that the elimination of the spots is a slow
process (weeks, months).
The way of the depigmenting agents to reach the melanosomes is by passive
diffusion process through stratum corneum. So, they are limited by the very
low permeability of it.
The negative stimulus produced by UV radiation must be abolish using sun
filter.
Due to the reversible inhibition of tyrosinase, the application on the skin of
the depigmenting products must be made very frequently and for a long
period.
Would be more rational to use substances working on the spot by dissolution,
complexation, mobilization, etc., but till today does not exists any safety
product acting in this way, probably due to the high chemical stability of the
melanins.
According the above described mechanism, it seems that it is impossible to
eliminate the dermal spots. However the activity of macrophagic cells
(scavenger) gets mobilize slowly these abnormal amount of melanins in
dermal areas.
IV. Cosmelan 1 & Cosmelan 2
•
•
•
•
•
Legal Status: Cosmetic Product
Commercial Presentation: Pack
– Cosmelan 1: Mask – Jar containing 10 g
– Cosmelan 2: Maintenance cream – Jar containing 30 g
– Degreasing Solution: Bottle containing 10 ml
Cosmetic Preparation: Emulsions type O/W (mask & cream).
Properties:
– Skin depigmentation
– Skin lightening
– Skin embellishment
Complementary products:
– Moisturizing: ms Hydravital Factor K
– Sunscreen: ms Pantalla Total Hidratante (SPF 30)
IV. Cosmelan 1 & Cosmelan 2
Description
•
•
•
The same qualitative composition in functional cosmetic ingredients.
Higher concentration of depigmenting agents in mask.
They are applied on the skin in different ways.
•
In both cosmetic products:
– More than 50% of the formula are formed by functional cosmetic
ingredients.
– This high concentration has the purpose to create an elevated
gradient of depigmenting agents in the stratum corneum as a
good driving force to improve the passive diffusion of active
ingredients.
– This effect will be leaded to have an effective concentration of
depigmenting agents inside melanocytes and a critical and
effective concentration inside melanosomes.
IV. Cosmelan 1 & Cosmelan 2
Functional Composition
A. SUN FILTERS: Abolish the melanogenesis UV strong stimulus
a. Organic Filters:
i. Protection against UVB radiation (290 – 320 nm)
ii. Protection against UVA radiation (320 – 400 nm)
b. Inorganic Filter:Protection against UVB/A radiation (290 –400
nm).
i. Incorporate a new non-whitening inorganic filter with broad
sepectrumUVA/UVB
producing
minimal
free-radiacals
generation (TiO2/Mn). Enhance photostability of organic
filter.
c. Sun Protection Factor (SPF) = 20 (UVA+++)
IV. Cosmelan 1 & Cosmelan 2
Functional Composition
A.
.
B. NON-CYTOTOXICS REVERSIBLE TYROSINASE INHIBITORS:
• Azelaic Acid:
Competitive inhibitor of tyrosinase. Bacteriostatic against aerobic
& anaerobic microorganisms. Competitive inhibitor of 5-alpha
reductase reducing cutaneous sebum production.
• Kojic Acid:
Competitive inhibitor of tyrosinase. Antioxidant. Scavenges ROS.
Bacteriostatic.
• Alpha-arbutine:
Competitive inhibitor of tyrosinase. Enantiomer of natural betaarbutin (ten times more potent and chemically more stable).
• Rumex Canadiensis Extract:
Competitive inhibitor of tyrosinase. Skin anti-erythema.
IV. Cosmelan 1 & Cosmelan 2
Functional Composition
A.
.
B. NON-CYTOTOXICS REVERSIBLE TYROSINASE INHIBITORS:
• Tyrosinol Complex:
Competitive inhibitor of tyrosinase.
• Aloesine (Aloe Barbadensis):
Competitive inhibitor of tyrosinase.
• Glabridin (Licorice Extract):
Competitive inhibitor of tyrosinase. Skin lightening.
• Sodium Ascorbyl Phosphate:
Stable derivative of Ascorbic Acid. Avoids melanin formation by
reducing o-quinones. Skin lightening.
IV. Cosmelan 1 & Cosmelan 2
Functional Composition
A.
.
C. OTHER EFFECTS ON MELANOGENESIS PROCESS:
• Azelaic Acid:
Antiproliferative and cytotoxic effects on hyperplasic melanocites.
• Niacinamide:
Stops melanosomas transfer to keratinocytes.
• Aminoethylphosphinic Acid:
Specific DOPA-tautomerase inhibitor.
• Tyrosinol Complex:
Tyrosine Related Protein (TPR1) inhibitor (eumelanins metabolic
pathway).
• Nonapeptide-1:
Biomimetic peptide specific antagonist of the alpha-MSH, due to
its high affinity for cell melanotropin receptor (MC-1R) producing
reversible inhibition. Inhibit the UV / alpha-MSH induced melanins
biosynthesis.
IV. Cosmelan 1 & Cosmelan 2
Functional Composition
A.
.
D. SKIN BEAUTY AGENTS:
• Retinol:
Promotes fibroblastic activities. Antioxidant. Stimulates the
epidermal kinetic. Prevents wrinkles and free radicals formation.
• Tocopherol:
Antioxidant. Protects cell membranes from lipidic peroxidation.
Avoids collagen crosslinked and protein glycation (antiaging
effect).
• Ascorbic Acid:
Stimulates collagen formation and increases the fibroblastic
activity.
Free radicals neutralizer.
• Aloe Barbadensis:
Moisturizing and skin revitalizer.
IV. Cosmelan 1 & Cosmelan 2
Functional Composition
A.
.
E. SKIN PENETRATION ENHANCERS:
• Bisabolol & Ethoxydiglycol:
Promotes the stratum corneum permeability to functional
ingredients, improving its passive diffusion and higher epidermal
concentration.
F. MELANINS ELIMINATION ACCELERATOR.
• Salicylic Acid:
Exfoliant agents that promotes the turnover of korneocytes.
V. Application Protocol
A.
.
1. Proffessional Treatment (Beauticien):
• Cleaning the skin surface with Degreasing Solution.
Soak in a gauze the solution and rub the skin surface to treat gently
trying to leave the skin very well clean.
• Apply the content of the jar Cosmelan 1 in face and neck like a mask.
• Standard period of action: let the product acting for 8 hours on the skin.
Depending of the skin type, this period may be expand to 12 hours
2. In House Treatment:
• Apply on the skin to treat Cosmelan 2 (cream) twice per day during 8
weeks.
Morning: keep it minimum 3 hours
Night: keep it all the night
9th week in advance: one time during night
• This standard treatment protocol may be reinforced depending on the
results of the “skin reading” during treatment.
V. Application Protocol
Comments
A.
.
1. Due to the depigmenting effect is depending on the concentration of
active ingredients on melanosomes, the amount of the cosmetic
product applied on the skin matters in the effectiveness.
2. Suitable doses is about 2 mg of cream per cm2 of skin. That means,
for face, the minimal dose should be about 0,5 g of cream per
application.
3. The enzymatic tyrosinase inhibition is a reversible process. So, the
treatment must be maintained without interruptions even with skin
erythema.
4. In some cases is advisable to apply a mask session (Cosmelan 1)
each month.
VI. Results
A.
.
1. Significant attenuation, diminution or disappearance of melanic spot
at the third or fourth week of treatment.
2. Renovation and embellishment of the skin at the second week of
treatment.
3. Stimulation of capillary circulation giving an effect of the new skin
luminous, pink , smooth and shining.
VI. Results - Pictures
Group Body_esthetic Laboratories
Thanks a lot for your attention