Download A Multi-Mechanism Skin Brightening Regimen Delivers

A Multi-Mechanism Skin Brightening Regimen Delivers Pigment Evening Benefits in an Ethnically Diverse Population
Brenda L. Edison BA, Barbara A. Green RPh, MS, Lisa Buckley BA, Irina Brouda MA, Peter N. Konish MS, Yaling Lee PhD, Ronni L. Weinkauf PhD
NeoStrata Company, Inc., Princeton, NJ, USA
Introduction
Objective
To evaluate the tolerability and lightening / brightening benefits of a high-strength twicedaily skincare regimen in normally pigmented and hyperpigmented skin in an ethnically
diverse population of women with uneven facial pigmentation.
Study Methodology
Subject Demographics
100
Subjects (n)
30
Gender
Female
Age, mean (range)
Percentage (%) that Agree Somewhat,
Agree Very Much, Highly Agree
Pigmentation irregularities are a major concern for many ethnic skin populations spanning
the globe.1,2 Safe, effective, and aesthetically pleasing formulations that can even skin
color, brighten skin tone, and reduce dark spots are requested by dermatology patients
around the world.3 A new brightening skincare regimen was developed to improve
the complexion of facial skin by targeting multiple steps and pathways that affect
pigmentation. The regimen consists of a facial cleanser, serum, and lotion, which contain
N-Acetylglucosamine4 plus a variety of other benefit ingredients to collectively exfoliate
pigmented areas, reduce tyrosinase activity and melanin production, and deliver an overall
pigment evening effect.
50 (37–60)
Race/Ethnicity, n (%)
Latin American
14 (47%)
Caucasian
10 (33%)
Pacific Rim Asian
3 (10%)
African American
2 (7%)
Indian
1 (3%)
Population / Inclusion
Criteria
Women, 30–60 years old, Fitzpatrick skin types I-IV, all ethnicities, with areas of mild to
moderate facial hyperpigmentation (3–7 on a 10 cm visual analog scale), epidermal in
nature (confirmed by Wood’s Lamp), willing to limit sun exposure and not change
hormonal medications
Exclusion Criteria
Allergies to skincare product ingredients; use of hydroxyacids, retinol, hydroquinone, kojic
acid and other antiaging or lightening/brightening cosmetics within last 2 months; cosmetic
procedures or routine use of antiaging or skin brightening topical medications, including
prescription retinoids, within last 6 months; planned or current pregnancy; breast-feeding
Study Duration
16 weeks
Study Regimen
Twice a day use of the cleanser, serum, and lotion on the entire face
(standard facial sunscreen provided for as needed use)
Evaluation Visits
Weeks 0, 4, 8, and 16
Evaluation Tools
– Visual grading by a trained clinical grader using a 10 cm visual analog scale from
extremely uneven skin tone (0) to even skin tone (10)
• Objective
– Chromameter measurements of brightness (L*) and sallowness (yellow hue, b*)
of normally pigmented and hyperpigmented areas (weeks 0, 8, and 16 only)
– Digital clinical photographs of the face
• Subjective
– Subject self-assessment questionnaires
• 4% N-Acetylglucosamine (NeoGlucosamine®)a,b
• Swiss alpine plant extracts (GigaWhite®)b,c
• 4% N-Acetylglucosamine (NeoGlucosamine)a,b
• Swiss alpine plant extracts (GigaWhite)b,c
erum
S
(NeoStrata® Enlighten
Illuminating Serum)
• Oligopeptide-34b,c
• Tetrahexyldecyl Ascorbate (Vitamin C)b,c
Week 8
40
Week 16
30
20
10
0
n=30
Skin is more
evenly colored
Brown spots
are less apparent
Skin has better
clarity / radiance
5a
 Subject photographs (Figs. 3, 4, and 5) show lighter and more even skin color, a brighter
overall skin tone, and less apparent brown spots after regimen use.
– Brightness (L*):
• N
ormally pigmented skin achieved fast improvement in brightness (week 8, 16),
P<0.01
• H
yperpigmented skin achieved strong improvement in brightness by week 16,
P<0.01
• N
ormally pigmented skin and hyperpigmented skin achieved comparable increases
in brightness by week 16
5c
otion
L
(NeoStrata® Enlighten
Pigment Controller)
Week 0
Normally Pigmented Skin
Week 8
63
*†
*
Week 16
3a
Baseline
62
61
60
59
58
57
*†
†‡
A new multi-ingredient brightening skincare regimen was tested in an ethnically
diverse sample of women with uneven facial pigmentation. Women applied the
regimen to the entire face twice a day for 16 weeks.
3b
Week 16
Visual grading and clinical photographs showed:
 Lighter and more even skin color
 Brighter overall skin tone
 Reduced overall sallowness
 Lighter and less apparent brown spots
 Effects were observed in all ethnic groups
Figure 4.
Hyperpigmented Skin
Chromameter analyses of normally pigmented areas and brown spots
showed that:
 Both normally pigmented areas and brown spots became brighter and less sallow
 Normally pigmented areas brightened faster than brown spots
 Brown spots improved in sallowness faster and to a greater degree than normally
pigmented areas
Decreased Sallowness
56
19
18
Yellow b* values
17
16
Self-assessment questionnaires confirmed that subjects noticed brighter skin tone,
more even pigmentation, and less apparent brown spots
Subject Self-Assessment
• Ascorbyl Glucoside (Vitamin C)b,c
• T
etrahydrodiferuloylmethane (curcumin analogue found
naturally in tumeric, SabiWhite®)b,c

Subjects reported more even pigmentation, less obvious brown spots, and improved
clarity and radiance at each post-baseline visit (Fig. 2)
Exfoliant; bTyrosinase Inhibitor; cMelanin Reducer
a
Week 16
For the subject in Figure 5 above, note improvement in pigmentation in standard
lighting photographs (5a, 5b) and in cross-polarized photographs with melanin imaging
applied to visualize hyperpigmented areas (5c, 5d).
Summary
64
 Subjects reported brighter overall skin tone during regimen use:
– 60% of subjects noticed an improvement as early as 2 weeks
– 9
0% of subjects rated excellent, very good or good improvement after
16 weeks
• 0.1% Retinolb,c
5d
Baseline
• Licorice Extractb
• Swiss alpine plant extracts (GigaWhite)b,c
Week 16
Figure 3.
Figure 1. Improvement in Brightness and Sallowness of
Normally Pigmented and Hyperpigmented Skin
• Eucommia Ulmoides Leaf Extract (source of chlorogenic acid)c
• 6% N-Acetylglucosamine (NeoGlucosamine) a,b
5b
Baseline
– Sallowness (b*)
• N
ormally pigmented skin was significantly less sallow at week 16, P<0.01
• H
yperpigmented skin was significantly less sallow at weeks 8 and 16, P<0.01
• H
yperpigmented skin achieved a significantly greater reduction in sallowness than
normally pigmented skin at week 8, P<0.05
Luminance L* values
Key Benefit Ingredients
leanser
C
(NeoStrata® Enlighten Ultra
Brightening Cleanser)
Week 4
50
 Normally pigmented skin and hyperpigmented skin (brown spots) showed significantly
increased brightness and decreased sallowness (Fig. 1):
Observed and reported adverse events
Product
60
Clinical Photography
– Chromameter change from baseline comparisons for hyperpigmented vs normally
pigmented skin using paired t-tests at P<0.05
Study Products
80%
77%
Chromameter Measurements
– Tabulation of subject self-assessment scores
Safety
80%
70
 Significant improvement in evenness of skin tone was observed at every post-baseline
visit (weeks 4, 8, and 16, P<0.0001)
– Before and after treatment comparisons of visual grading scores and chromameter
measurements using ANOVA followed by a Dunnett’s test at P<0.05
Statistics
80
 The high-strength regimen was well-tolerated. Adverse reactions were mild (n=3) to
moderate (n=3) localized skin irritation, mostly within the first 2 weeks of use, and may
have been due to twice-daily use of retinol without an acclimation phase. Reactions
were distributed across ethnicities.
Increased Brightness
Single-group, prospective skincare regimen use study with direct comparisons to baseline
90
Tolerability
Visual Grading
 93% of users achieved a more even skin tone after the first 4 weeks
Study Design
Figure 5.
Figure 2. Subject Self-Assessment of
Improvement in Skin Pigmentation
Results
References
1.
2.
3.
4.
4a
Baseline
4b
Week 16
Cole PD, Hatef DA, Taylor S, Bullocks JM. Skin care in ethnic populations. Semin Plast Surg. 2009 Aug;23(3):168-72.
Grimes PE. Management of hyperpigmentation in darker racial ethnic groups. Semin Cutan Med Surg. 2009 Jun;28(2):77-85.
Taylor SC. Cosmetic problems in skin of color. Skin Pharmacol Appl Skin Physiol. 1999 May-Jun;12(3):139-43.
Hwang JS, Lee HY, Lim TY, Kim MY, Yoon TJ. Disruption of tyrosinase glycosylation by N-acetylglucosamine and its depigmenting effects
in guinea pig skin and in human skin. J Dermatol Sci. 2011 Sep;63(3):199-201.
Poster presented at the 21st Congress of the European Academy of Dermatology
& Venereology, Prague, Czech Republic, 27–30 September, 2012
Study sponsored by NeoStrata Company, Inc., Princeton, NJ, USA
P248
A Multi-Mechanism Skin Brightening
Regimen Delivers Pigment Evening
Benefits in an Ethnically Diverse
Population
Brenda L. Edison BA
Barbara A. Green RPh, MS
Lisa Buckley BA
Irina Brouda MA
Peter N. Konish MS
Yaling Lee PhD
Ronni L. Weinkauf PhD
NeoStrata Company, Inc., Princeton, NJ, USA
21st Congress of the European Academy of
Dermatology & Venereology
Prague, Czech Republic, 27-30 September, 2012
P248
Introduction
Results
Pigmentation irregularities are a major concern for many ethnic skin populations spanning
the globe.1,2 Safe, effective, and aesthetically pleasing formulations that can even skin
color, brighten skin tone, and reduce dark spots are requested by dermatology patients
around the world.3 A new brightening skincare regimen was developed to improve
the complexion of facial skin by targeting multiple steps and pathways that affect
pigmentation. The regimen consists of a facial cleanser, serum, and lotion, which contain
N-Acetylglucosamine4 plus a variety of other benefit ingredients to collectively exfoliate
pigmented areas, reduce tyrosinase activity and melanin production, and deliver an overall
pigment evening effect.
Objective
To evaluate the tolerability and lightening / brightening benefits of a high-strength twicedaily skincare regimen in normally pigmented and hyperpigmented skin in an ethnically
diverse population of women with uneven facial pigmentation.
Study Methodology
Subject Demographics
Subjects (n)
30
Gender
Fem
Age, mean (range)
50 (
Race/Ethnicity, n (%)
Latin American
14 (
Caucasian
10 (
Pacific Rim Asian
3 (1
African American
2 (7
Indian
1 (3
Visual Grading
 93% of users achieved a more even sk
Single-group, prospective skincare regimen use study with direct comparisons to baseline
Population / Inclusion
Criteria
Women, 30–60 years old, Fitzpatrick skin types I-IV, all ethnicities, with areas of mild to
moderate facial hyperpigmentation (3–7 on a 10 cm visual analog scale), epidermal in
nature (confirmed by Wood’s Lamp), willing to limit sun exposure and not change
hormonal medications
Exclusion Criteria
Allergies to skincare product ingredients; use of hydroxyacids, retinol, hydroquinone, kojic
acid and other antiaging or lightening/brightening cosmetics within last 2 months; cosmetic
procedures or routine use of antiaging or skin brightening topical medications, including
prescription retinoids, within last 6 months; planned or current pregnancy; breast-feeding
Study Duration
16 weeks
Study Regimen
Twice a day use of the cleanser, serum, and lotion on the entire face
(standard facial sunscreen provided for as needed use)
Evaluation Visits
Weeks 0, 4, 8, and 16
Evaluation Tools
– Visual grading by a trained clinical grader using a 10 cm visual analog scale from
extremely uneven skin tone (0) to even skin tone (10)
• Objective
– Chromameter measurements of brightness (L*) and sallowness (yellow hue, b*)
of normally pigmented and hyperpigmented areas (weeks 0, 8, and 16 only)
– Digital clinical photographs of the face
• Subjective
– Subject self-assessment questionnaires
 Significant improvement in evenness o
visit (weeks 4, 8, and 16, P<0.0001)
Chromameter Measurements
 Normally pigmented skin and hyperpig
increased brightness and decreased s
– Brightness (L*):
• Normally pigmented skin achieve
P<0.01
• Hyperpigmented skin achieved st
P<0.01
• Normally pigmented skin and hyp
in brightness by week 16
– Sallowness (b*)
• Normally pigmented skin was sig
• Hyperpigmented skin was signific
• Hyperpigmented skin achieved a
normally pigmented skin at week
– Before and after treatment comparisons of visual grading scores and chromameter
measurements using ANOVA followed by a Dunnett’s test at P<0.05
Statistics
Figure 1. Improvement in
Normally Pigmented
– Chromameter change from baseline comparisons for hyperpigmented vs normally
pigmented skin using paired t-tests at P<0.05
– Tabulation of subject self-assessment scores
Study Products
Product
Key Benefit Ingredients
Cleanser
(NeoStrata® Enlighten Ultra
Brightening Cleanser)
• 4% N-Acetylglucosamine (NeoGlucosamine®)a,b
• Swiss alpine plant extracts (GigaWhite®)b,c
• 4% N-Acetylglucosamine (NeoGlucosamine)a,b
• Swiss alpine plant extracts (GigaWhite)b,c
Serum
(NeoStrata® Enlighten
Illuminating Serum)
64
Observed and reported adverse events
• Oligopeptide-34b,c
• Tetrahexyldecyl Ascorbate (Vitamin C)b,c
Week 0
Week 8
63
Luminance L* values
Safety
Week 16
62
Increased Brightness
Study Design
61
60
59
58
57
Decrea
56
19
18
• Eucommia Ulmoides Leaf Extract (source of chlorogenic acid)c
Y
• Licorice Extractb
• 6% N-Acetylglucosamine (NeoGlucosamine) a,b
Lotion
(NeoStrata® Enlighten
Pigment Controller)
Subject Self-Assessment
• Ascorbyl Glucoside (Vitamin C)b,c
 Subjects reported brighter overall skin
– 60% of subjects noticed an improve
– 90% of subjects rated excellent, ver
16 weeks
• Tetrahydrodiferuloylmethane (curcumin analogue found
naturally in tumeric, SabiWhite®)b,c
 Subjects reported more even pigment
clarity and radiance at each post-bas
• Swiss alpine plant extracts (GigaWhite)b,c
• 0.1% Retinol
b,c
Exfoliant; bTyrosinase Inhibitor; cMelanin Reducer
a
P248
gimen use study with direct comparisons to baseline
skin types I-IV, all ethnicities, with areas of mild to
–7 on a 10 cm visual analog scale), epidermal in
willing to limit sun exposure and not change
nts; use of hydroxyacids, retinol, hydroquinone, kojic
/brightening cosmetics within last 2 months; cosmetic
g or skin brightening topical medications, including
onths; planned or current pregnancy; breast-feeding
m, and lotion on the entire face
or as needed use)
rader using a 10 cm visual analog scale from
en skin tone (10)
ghtness (L*) and sallowness (yellow hue, b*)
gmented areas (weeks 0, 8, and 16 only)
ce
aires
Subject Demographics
Subjects (n)
30
Gender
Female
Age, mean (range)
50 (37–60)
Race/Ethnicity, n (%)
Latin American
14 (47%)
Caucasian
10 (33%)
Pacific Rim Asian
3 (10%)
African American
2 (7%)
Indian
1 (3%)
nt extracts (GigaWhite)b,c
,c
Ascorbate (Vitamin C)b,c
osamine (NeoGlucosamine) a,b
60
50
40
30
20
10
0
Skin is more
evenly colored
Bro
are le
Clinical Photography
 Normally pigmented skin and hyperpigmented skin (brown spots) showed significantly
increased brightness and decreased sallowness (Fig. 1):
 Subject photographs (Figs. 3, 4, and 5
overall skin tone, and less apparent br
– Brightness (L*):
• Normally pigmented skin achieved fast improvement in brightness (week 8, 16),
P<0.01
• Hyperpigmented skin achieved strong improvement in brightness by week 16,
P<0.01
• Normally pigmented skin and hyperpigmented skin achieved comparable increases
in brightness by week 16
F
– Sallowness (b*)
• Normally pigmented skin was significantly less sallow at week 16, P<0.01
• Hyperpigmented skin was significantly less sallow at weeks 8 and 16, P<0.01
• Hyperpigmented skin achieved a significantly greater reduction in sallowness than
normally pigmented skin at week 8, P<0.05
Figure 1. Improvement in Brightness and Sallowness of
Normally Pigmented and Hyperpigmented Skin
64
Week 0
Luminance L* values
Normally Pigmented Skin
Week 8
63
*†
*
Week 16
3a
Baseline
62
61
60
59
58
57
*†
†‡
F
Hyperpigmented Skin
Decreased Sallowness
56
19
18
des Leaf Extract (source of chlorogenic acid)c
Yellow b* values
17
16
Subject Self-Assessment
de (Vitamin C)b,c
 Subjects reported brighter overall skin tone during regimen use:
– 60% of subjects noticed an improvement as early as 2 weeks
– 90% of subjects rated excellent, very good or good improvement after
16 weeks
oylmethane (curcumin analogue found
ic, SabiWhite®)b,c
 Subjects reported more even pigmentation, less obvious brown spots, and improved
clarity and radiance at each post-baseline visit (Fig. 2)
nt extracts (GigaWhite)b,c
70
Chromameter Measurements
ts
osamine (NeoGlucosamine)a,b
80%
 Significant improvement in evenness of skin tone was observed at every post-baseline
visit (weeks 4, 8, and 16, P<0.0001)
nt scores
nt extracts (GigaWhite®)b,c
80
 The high-strength regimen was well-to
moderate (n=3) localized skin irritation
have been due to twice-daily use of re
were distributed across ethnicities.
 93% of users achieved a more even skin tone after the first 4 weeks
comparisons for hyperpigmented vs normally
at P<0.05
osamine (NeoGlucosamine®)a,b
90
Tolerability
Visual Grading
sons of visual grading scores and chromameter
ed by a Dunnett’s test at P<0.05
dients
100
Percentage (%) that Agree Somewhat,
Agree Very Much, Highly Agree
ning benefits of a high-strength twicehyperpigmented skin in an ethnically
gmentation.
Figure 2. Subje
Improvement
Results
Increased Brightness
many ethnic skin populations spanning
ing formulations that can even skin
e requested by dermatology patients
men was developed to improve
steps and pathways that affect
nser, serum, and lotion, which contain
fit ingredients to collectively exfoliate
elanin production, and deliver an overall
NeoStrata Company, Inc., Princeton, NJ, USA
4a
Baseline
P248
NeoStrata Company, Inc., Princeton, NJ, USA
F
Figure 2. Subject Self-Assessment of
Improvement in Skin Pigmentation
Percentage (%) that Agree Somewhat,
Agree Very Much, Highly Agree
100
90
80
80%
80%
77%
70
60
Week 4
50
Week 8
40
Week 16
30
20
10
0
n=30
Skin is more
evenly colored
Brown spots
are less apparent
Skin has better
clarity / radiance
5a
Tolerability
ter the first 4 weeks
e was observed at every post-baseline
Baseline
 The high-strength regimen was well-tolerated. Adverse reactions were mild (n=3) to
moderate (n=3) localized skin irritation, mostly within the first 2 weeks of use, and may
have been due to twice-daily use of retinol without an acclimation phase. Reactions
were distributed across ethnicities.
Clinical Photography
kin (brown spots) showed significantly
(Fig. 1):
 Subject photographs (Figs. 3, 4, and 5) show lighter and more even skin color, a brighter
overall skin tone, and less apparent brown spots after regimen use.
Figure 3.
rovement in brightness (week 8, 16),
ovement in brightness by week 16,
ted skin achieved comparable increases
ess sallow at week 16, P<0.01
sallow at weeks 8 and 16, P<0.01
ly greater reduction in sallowness than
5c
Baseline
For the subject in Figure 5 above, n
lighting photographs (5a, 5b) and in cr
applied to visualize h
ness and Sallowness of
yperpigmented Skin
Summary
Normally Pigmented Skin
*†
*
3a
Baseline
*†
A new multi-ingredient brightening sk
diverse sample of women with uneve
regimen to the entire face twice a da
3b
Week 16
Visual grading and clinical photogra
 Lighter and more even skin color
 Brighter overall skin tone
 Reduced overall sallowness
 Lighter and less apparent brown
 Effects were observed in all ethni
Figure 4.
Hyperpigmented Skin
Chromameter analyses of normally
showed that:
 Both normally pigmented areas a
 Normally pigmented areas brighte
 Brown spots improved in sallown
pigmented areas
wness
lues
17
16
Self-assessment questionnaires con
more even pigmentation, and less app
References
ng regimen use:
arly as 2 weeks
good improvement after
s obvious brown spots, and improved
Fig. 2)
1.
2.
3.
4.
4a
Baseline
4b
Week 16
Cole PD, Hatef DA, Taylor S, Bullocks JM. Skin care in ethni
Grimes PE. Management of hyperpigmentation in darker rac
Taylor SC. Cosmetic problems in skin of color. Skin Pharmac
Hwang JS, Lee HY, Lim TY, Kim MY, Yoon TJ. Disruption of t
in guinea pig skin and in human skin. J Dermatol Sci. 2011 S
Poster presented at the 21st Congress of the European A
& Venereology, Prague, Czech Republic, 27–30 Septemb
Study sponsored by NeoStrata Company, Inc., Princeton
P248
S, Yaling Lee PhD, Ronni L. Weinkauf PhD
Figure 5.
f-Assessment of
n Pigmentation
t
80%
Week 4
Week 8
Week 16
n=30
Skin has better
clarity / radiance
5a
5b
Baseline
Adverse reactions were mild (n=3) to
within the first 2 weeks of use, and may
out an acclimation phase. Reactions
Week 16
hter and more even skin color, a brighter
s after regimen use.
3.
5c
Baseline
Week 16
For the subject in Figure 5 above, note improvement in pigmentation in standard
lighting photographs (5a, 5b) and in cross-polarized photographs with melanin imaging
applied to visualize hyperpigmented areas (5c, 5d).
Summary
A new multi-ingredient brightening skincare regimen was tested in an ethnically
diverse sample of women with uneven facial pigmentation. Women applied the
regimen to the entire face twice a day for 16 weeks.
Week 16
Visual grading and clinical photographs showed:
 Lighter and more even skin color
 Brighter overall skin tone
 Reduced overall sallowness
 Lighter and less apparent brown spots
 Effects were observed in all ethnic groups
4.
Week 16
5d
Chromameter analyses of normally pigmented areas and brown spots
showed that:
 Both normally pigmented areas and brown spots became brighter and less sallow
 Normally pigmented areas brightened faster than brown spots
 Brown spots improved in sallowness faster and to a greater degree than normally
pigmented areas
Self-assessment questionnaires confirmed that subjects noticed brighter skin tone,
more even pigmentation, and less apparent brown spots
References
1.
2.
3.
4.
Cole PD, Hatef DA, Taylor S, Bullocks JM. Skin care in ethnic populations. Semin Plast Surg. 2009 Aug;23(3):168-72.
Grimes PE. Management of hyperpigmentation in darker racial ethnic groups. Semin Cutan Med Surg. 2009 Jun;28(2):77-85.
Taylor SC. Cosmetic problems in skin of color. Skin Pharmacol Appl Skin Physiol. 1999 May-Jun;12(3):139-43.
Hwang JS, Lee HY, Lim TY, Kim MY, Yoon TJ. Disruption of tyrosinase glycosylation by N-acetylglucosamine and its depigmenting effects
in guinea pig skin and in human skin. J Dermatol Sci. 2011 Sep;63(3):199-201.
Poster presented at the 21st Congress of the European Academy of Dermatology
& Venereology, Prague, Czech Republic, 27–30 September, 2012
Study sponsored by NeoStrata Company, Inc., Princeton, NJ, USA
P248
P248