Fine Lines, Wrinkles & Texture Research Update - P&G Beauty ...

Peptides
Th e use of peptides in commercial
products has signifi cantly risen in
recent years. Known to play a role in
wound-healing, naturally occurring
peptides in the skin have been shown in
vitro to: (1) stimulate the production
of extracellular matrix components
including collagen, elastin and fi bronectin
and (2) decrease the production
of dermal GAGs. 49, 50 Decreased
dermal matrix components and
increased dermal GAGs are hallmark
features of aged skin, 51 the reversal of
which has been hypothesized as a viable
approach to anti-aging.
With variations in amino acid
sequence, number of amino acids
and use of derivatives of these acids,
there are limitless combinations of
possible peptides. By testing the eff ect
of multiple peptides on the synthesis
of collagen in culture, scientists
at the University of Tennessee
49, 50
narrowed the fi eld of possible amino
acid combinations to a pentapeptide
fragment of pro-collagen, KTTKS
(lysine-threonine-threonine-lysineserine).
Th is peptide retained 80%
of the collagen-stimulating activity
of the original, much larger 34–44
amino acid pro-collagen peptide
from which it was derived.
Because transdermal delivery of ionic
peptides is likely to pose a signifi cant
issue for delivery of bioactive peptide
into the skin, a palmitoyl derivative
14 Fine Lines, Wrinkles & Texture: Research Update
Collagen synthesis (% of control)
250 –
200 –
150 –
100 –
50 –
0
Control 4ppm pal-KTTKS
In cell culture experiments, pal-KTTKS increases
collagen synthesis.
–
–
of KTTKS (pal-KTTKS) was used,
which capitalizes on research conducted
on peptides to improve transcutaneous
delivery. 52
Consistent with the collagenstimulating
eff ects of the underivatized
KTTKS, pal-KTTKS promotes
the production of collagen in organotypic
cultures of human skin cells. 24
In addition, pal-KTTKS eff ectively
reduces dermal GAGs at 1/10 th the
dose of trans-retinoic acid (tRA). 53
Th e promotion of these eff ects in
vitro are consistent with the antiaging
strategy proposed above.
Multiple clinical studies have demonstrated
the signifi cant eff ect of formu
lations containing pal-KTTKS on
wrinkle reduction and facial appearance
improvement. In one study, 54
60 subjects were treated for four
months in a split-faced doubleblinded
trial. Th e pal-KTTKS
test product produced signifi cant
% reduction in GAGs
% change over 4 months
70 –
60 –
50 –
40 –
30 –
20 –
10 –
0
5 –
0 –
-5 –
-10 –
-15 –
-20 –
-25 –
-30 –
-35 –
-40
0.9ppm
pal-KTTKS
% change vs. To p< 0.01 % change vs. To p< 0.015
Wrinkle volume
(μm 3 )
–
5 –
0 –
-5 –
-10 –
-15 –
-20 –
-25 –
-30
¢ pal-KTTKS
¢ tRA control
10ppm tRA
(*10ppm = 0.001%)
In in vitro cell culture experiments, pal-KTTKS
reduces GAGs comparably at 1/10 th the dose of
tRA (10 ppm = 0.001%).
¢ pal-KTTKS
¢ Vehicle
Wrinkle depth
(μm)
Moisturizer containing pal-KTTKS decreases both
wrinkle volume and depth following 4 months of
treatment.
–
improve ments versus the vehicle in
wrinkle volume and wrinkle depth
at two- and four-month time points.
Results were based on quantitative
image analysis of skin replicas.
In another split-face double-blinded
study of 92 subjects, 27 signifi cant