Best practice in hyperpigmentation Innovation – Performance – Safety PDF compression, OCR, web optimization using a watermarked evaluation copy of CVISION PDFCompressor
Best practice in hyperpigmentation
Innovation – Performance – Safety
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Why do we use skin whitening?In case of lighten age-spot and hyperpigmen-tation: All over the world skin whitening is seen more as a part of anti-aging treatment, to hide undesirable signs of ageing from the skin like age spots, unhealthy life-style and pollution.
Pigmentation is determined by the amount and type of melanin in the skin and can be influenced by: • Genetic constitutive pigmentation (African,
Asian, Caucasian) • Facultative pigmentation: UV exposure via
α-MSH activation
Skin pigmentation pathways:
lamelat™ Targeted Action Majority of whitening agents act only on Tyrosinase and, thus, they modulate only one component of the pigmentation process.
lamelat™ - Main Action on MITF and can modulate the complete pathways of pigmentation.
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Skin Whitening Pathways Unique whitening pathway via MITF
lamelat™ binds specifically to the TGF-β receptor.
Modulation of the Constitutive Pigmentation Pathway Test Protocol: Melanocytes were incubated with lamelat™ at 0.01% for 30 minutes. Intracellular proteins were extracted.
Proteins are transferred to a membrane and detected using antibodies specific to MITF and tyrosinase with western blot methodology• MITF1: regulation melanin production• Tyrosinase: 2
1 microphthalmia-associated transcription factor
0
20
40
60
120
80
100
50 100 150 200
TFG-b binding capacity
receptor
TGF-β
β
125I-TGF-
lamelat™
No free radiolabeled 125I-TGF-β100% Binding of the radiolabeled 125
0% binding of lamelat™
No free radiolabeled 125I-TGF-β0% Binding of the radiolabeled 125
100% binding of lamelat™
β-White™
TGF-βreceptor
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Modulation of the Facultative Pigmentation PathwayTest Protocol: Melanocytes were incubated with a-MSH and lamelat™ at different concentrations (0,01 – 0,1 – 1%) for 2 hours.Intracellular RNA is extracted and quantified by RT-PCR methodology Specific antibodies were used to detected TRP-1, TRP-2 and MITF genes expression.TRP-1 & TRP-2 (3): enzymes implicated in melanin production.
2 key enzyme involved in melanin production3 Tyrosinase related protein
lamelat ™ decreases proteins implicated in the facultative pigmentation.
Western Blot analysis on B16F10 melanocytes
lamelat™ decreases MITF and tyrosinase expression.lamelat™ decreases proteins expression implicated in the constitutive pigmentation.
MITF
Tyrosinase
WHITENING PEPTIDE decreases MITF, TRP-1 and TRP-2 expression in a dose dependant manner
Baseline WHITENING PEPTIDE 0.01%
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Inhibition of Tyrosinase ActivityTest Protocol: Melanocytes were incubated with a-MSH and lamelat™ at different concentrations (0,01 – 0,1) for 4 days.Intracellular proteins were extracted and labelled with L-DOPA.The tyrosinase activity4 is evaluated by measuring the L-DOPA absorbance at 405 nm.
lamelat™ decreases tyrosinase activity in a dose dependent manner.lamelat™ decreases the tyrosinase activity, thus reducing skin pigmentation.
Inhibition of Melanin Synthesis Test Protocol: Melanocytes were incubated with a-MSH and lamelat™ at different concentrations (0,01 – 0,1 – 1%) for 4 days.Intracellular proteins were extracted.The melanin pigment is detected by measuring the absorbance at 400 nm (melanin synthesis = amount of brown pigment).
4 tyrosinase activity = amount of L-DOPA
lamelat ™ decreases melanin synthesis for an optimal whitening and brightening effect in a dose dependent manner.
TYROSINE DOPA DOPAquinone MELANIN (Pheomelanin & Eumelanin)
TYROSINASE
a-MSH
40
80
120
160
Melanin synthesis in melanocytes
-44%
-65%-79%
baseline 0,01% 0,1% 1%
α-MSH + WHITENING PEPTIDE
0
40
80
120
160
Baseline 0,01% 0,1%
-38%
-60%
Tyrosinase activity in melanocytes
α-MSH100mg/mL
α-MSH + WHITENING PEPTIDE
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lamelat™ Recommendation:During the day, it is recommended to use beauty products with SPF. For sensitive skin, prone to allergic reaction after using lamelat™ it is advisable to do a test – please apply a small amount of product onto sensitive place such as the inside of the elbow or behind the ear and observe the response to the cosmetic. If within 24 hours there will be a negative skin reaction (such as redness or itching) product should be discontinued and the patient should contact with the professional.
• lamelat™: Innovative and unique whitening agent containing 5% of whitening peptide - the highest effective dose.
• Effective combination of a TGF-β agonist peptide encapsulated in a liposome.
• Unique regulatory action on the MITF pathway to decrease constitutive and facultative pigmentation.
• Better than Arbutin and Vitamin C.• Outstanding clinical results: 100% lightening
effect.• Excellent safety profile.
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Changes in melanocytes: Dendricity & Melanosome content lamelat™
Test Protocol: Melanocytes were incubated with a-MSH and lamelat™ at different concentrations (0,01 – 0,1%) for 4 days.The morphology of cells were examined by microscopy.The dentricity and the number of melanosomes can be observed.
lamelat™ prevents melanosome formation and thus, reduces the amount of melanin pigments for a lighter complexion.
Melanin Synthesis Comparative Study
Test Protocol: B16F10 melanocytes were incubated with 10μg/ml (1%) lamelat™, 10μg/ml Vitamin C, 10μg/ml Arbutin for 96 hours.Intracellular proteins were extracted.The melanin pigment is detected by measuring the absorbance at 400 nm.
lamelat™ decreases melanin synthesis with higher activity than Arbutin and Vitamin C.
0
25
50
75
100
Control Arbutin Vitamin C
-44%
-20% -19%
WHITENING PEPTIDE
WHITENING PEPTIDE has a higher efficacy than Arbutin and Vitamin C
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Clinical Efficacy on Skin Whitening / Lightening / Brightening
Test Protocol: Application of a Cream with 5% lamelat™, twice a day, for 56 days.Colorimetric measurements: analysis of the colorimetric parameter (L*) on the face at D0, D28 & D56 by spectrophotometer.Clinical evaluation by dermatologist investigators with a skin color scale at D0, D28 & D56.Questionnaire: closed questions on product efficacy at D0 & D56.
Skin Lightness (L*): is defined as the perceived brightness of an object compared to a perfect white object.
The L* value (luminance) gives the relative lightness ranging from total black (L=0) to total white (L=100).
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lamelat™ induces significant skin lightening effect after only 4 weeks.
Results on Skin Color Additional information on skin color evaluation: - 43% of people have skin score higher than 5 - 65 % of people have a reduction of 2.5 after 28 days
lamelat™ induces significant skin lightening effect.
lamelat™ reduces the appearance of pigmented spots.
Average reduction of 2.1 after 28 days.Average reduction of 3 after 56 days.
52
54
56
58
60
D0 D28 D56
L* v
alue
(lig
htne
ss)
+ 1.9% **
+ 2.9% **
** p<0.001
Skin Lightness (L*) Evaluation
100% of the subjects have a skin lightness increase!
5 3
D0 D28
5 2
D0 D56
D56 D28 D0
** p<0.001
1 2 3 4 5 6 7 8 9 10
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Results on Consumers Appreciation
INCI:Aqua, Butylene Glycol (and) Hydrogenated Lecithin (and) Sodium Oleate (and) Oligopep-tide-68 (and) Disodium EDTA, Caprylic/Capric Triglyceride, Glycerin, Mineral Oil, Dimeticone, Stearyl Alcohol, PEG-100 Stearate (and) Glyc-eryl Stearate, Butyrospermum Parkii (Shea But-ter), Glyceryl Stearate, Stearic Acid, Panthenol, Tocopherol Acetate, Allantoin, Parfum, Benzyl Alcohol (and) Methylchloroisothiazolinone (and) Methylisothiazolinone, Triethanolamine.
The skin tone is more uniform
Would like to purchase this product
The skin is brighter than before
Positive Opinion (%)
87%
91%
91%
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References:1. Hearing VJ. Biochemical control of melanogenesis and melanosomal organization. J Investig Dermatol Symp Proc. 1999 Sep; 4(1):24-8.
2. Hodgkinson CA, Moore KJ, Nakayama A, Steingrímsson E, Copeland NG, Jenkins NA, Arnheiter H. Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basichelix- loop-helix-zipper protein. .Cell. 1993 Jul 30; 74(2): 395-404.
3. Steingrímsson E, Moore KJ, Lamoreux ML, Ferré-D’Amaré AR, Burley SK, Zimring DC, Skow LC, Hodgkinson CA, Arnheiter H, Copeland NG, et al. Molecular basis of mouse microphthalmia (mi) mutations helps explain their developmental and phenotypic consequences. Nat Genet. 1994 Nov; 8(3): 256-63.
4. Hughes AE, Newton VE, Liu XZ, Read AP. A gene for Waardenburg syndrome type 2 maps close to the human homologue of the microphthalmia gene at chromosome 3p12-p14.1. Nat Genet. 1994 Aug;7(4): 509-12.
5. Bertolotto C, Bille K, Ortonne JP, Ballotti R. Regulation of tyrosinase gene expression by cAMP in B16 melanoma cells involves two CATGTG motifs surrounding the TATA box: implication of the microphthalmia gene product. J Cell Biol. 1996 Aug;134(3): 747-55.
6. Yasumoto K, Yokoyama K, Takahashi K, Tomita Y, Shibahara S. Functional analysis of microphthalmia associated transcription factor in pigment cell-specific transcription of the human tyrosinase family genes. J Biol Chem. 1997 Jan 3; 272(1): 503-9.
7. Tachibana M. MITF: a stream flowing for pigment cells. Pigment Cell Res. 2000 Aug; 13(4): 230-40.
8. Fang D, Tsuji Y, Setaluri V . Selective down-regulation of tyrosinase family gene TYRP1 by inhibition of the activity of melanocyte transcription factor, MITF. Nucleic Acids Res. 2002 Jul 15; 30(14): 3096-106.
9. Price ER, Horstmann MA, Wells AG, Weilbaecher KN, Takemoto CM, Landis MW, Fisher DE. alpha-Melanocyte-stimulating hormone signaling regulates expression of microphthalmia, a gene deficient in Waardenburg syndrome. J Biol Chem. 1998 Dec 4;273(49):33042-7.
10. Kim DS, Park SH, Park KC . Transforming growth factor-beta1 decreases melanin synthesis via delayed extracellular signal regulated kinase activation . Int J Biochem Cell Biol. 2004 Aug; 36(8): 1482-91.
11. Mol Biol Rep. 2008 Jul 4. Regulation of melanin synthesis by the TGF-beta family in B16 melanoma cells.Murakami M, Matsuzaki F, Funaba M.
12. J Biol Chem. 1997 Feb 14;272(7):3967-72. Transforming growth factor-beta1 inhibits basal melanogenesis in B16/F10 mouse melanoma cells by increasing the rate of degradation of tyrosinase and tyrosinase-related protein-1. Martínez-Esparza M, Jiménez-Cervantes C, Beermann F, Aparicio P, Lozano JA, García-Borrón JC.
13. Murakami M, Matsuzaki F, Funaba M. Regulation of melanin synthesis by the TGF-β family in B16 melanoma cells. Mol Biol Rep. 2008 Jul 4.
14. Martìnez-Esparza M, Jiménez-Cervantes C, Beermann F, Aparicio P, Lozano JA, Garcìa-Borrón JC. Transforming growth factor-beta1 inhibits basal melanogenesis in B16/F10 mouse melanoma cells by increasing the rate of degradation of tyrosinase and tyrosinase-related protein-1. J Biol Chem. 1997 Feb 14. 272 (7): 3967-72.
15.Yasumoto K, Yokoyanma K, Takahashi K, Tomita Y, Shibahara S. Functional analysis of microphatalmia-associated transcription factor in pigment cell-specific transcription of ther human tyrosianse family genes. J Biol Chem. 1997 Jan 3; 272(1): 503-509.
16. Tachibana M. MITF: a stream flowing for pigment cells. Pigment Cell res. 200 Aug; 13(4): 3096-3106.
17. Lambert J, Vancoillie G, Naeyaert JM. Molecular motors and their role in pigmentation. Cell Mol Biol. 1999 Nov; 45(7): 905-918.
PDF compression, OCR, web optimization using a watermarked evaluation copy of CVISION PDFCompressor
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