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Documente Cultură
doi: 10.1111/j.1468-2494.2012.00744.x
Review Article
Synopsis
In order to understand the skin benefits of emollient oil ingredients
in topical skin moisturizers, one single highly popular in vivo
method (corneometry), even when executed to perfection, does not
suffice. A systematical exploration using a combination of bioengineering techniques shows how a previously unaccounted for mechanism of moisturization by internal occlusion was discovered. As a
result, Isostearyl Isostearate turns out to be a highly functional
moisturizer when several methodologies are used.
sume
Re
Pour comprendre les benefices des huiles emollientes dans des
hydratants cutanes topiques, il ne suffit pas dutiliser une seule
methode in vivo pourtant tre`s populaire (corneometrie), meme si
elle est executee a` la perfection. Une exploration systematique utilisant une combinaison de techniques de bio-ingenierie montre comment un mecanisme dhydratation par occlusion interne jusque-la`
inconnu a ete decouvert. En consequence, lisostearyl-isostearate
save`re etre un hydratant hautement fonctionnel quand on utilise
plusieurs methodes danalyse.
Introduction
As a contribution to this commemorative issue, we have chosen to
review 10 years of research by Johann Wiechers on the function of
emollients in skin care emulsions.
Moving from a fundamental science environment into a cosmetic ingredients research position in 1995, the pharmacist
Wiechers was struck by the limited understanding of the effect and
performance on skin by so-called inert oil ingredients offered in
hundreds of different chemical flavours. He therefore undertook an
ambitious journey into unravelling step by step the functional
contributions of individual ingredients to a complete skin care
formulation.
Employed by a lipid-producing oleochemical company (Unichema,
now Croda), he started by studying the effect of emollients trying
to understand what exactly moisturizes the skin meant as a
Correspondence: Joseph C. Dederen, Croda Consumer Care Europe, Dorpsstraat 144a, B-3078 Meerbeek, Belgium. Tel.: +3227598951; fax:
+3227598953; e-mail: chris.dederen@croda.com
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environment (skin-to-skin, clothing-to-skin, etc.) and thereby alleviates possible sources of discomfort and irritation. Residual film thickness, dynamic spreading and oil viscosity can explain many but not
all of these lubrication effects. But skin is not an inert, rigid surface.
The compliant and elastic nature of living human skin tissue complicates the picture and the act of applying emollients introduces a
time dependence of the intrinsic friction properties: emollients
directly and indirectly modify the mechanical properties of skin and
adapted measuring methods had to be developed [1016].
By simply placing a dried piece of stratum corneum in different
liquid environments, Blank [17] realized already 60 years ago that
water is the most effective skin plasticizer and that neat emollient
oils do not have any plasticizing effect on dry skin (or on hair,
which is chemically comparable [18]). However, Blanks conclusions were erroneous at that time as he had not considered the
natural flux of water through the skin namely transepidermal
water loss (TEWL).
Because oil and water are sparingly miscible, it seemed logical
that applying a thin layer of oil on the skin surface could contribute to skin water-loss prevention by simple occlusion. Hence, by
reducing the water gradient in the upper layers of the skin, emollients can be considered as indirect skin moisturizers.
Moisturization is the most basic consumer expectation of a cosmetic skin care emulsion and therefore the most common functional cosmetic claim [19, 20]. The core challenge for any cosmetic
chemist is to master the water-binding capacity in the upper layers
of the skin and at the same time respect tactile sensory aesthetics
thereby delivering an improvement in the signs and symptoms of
dry skin. Again, the connection between skin mechanical properties, moisture gradient and individual classes of cosmetic ingredients was realized long time ago [21].
Emollients are not created equal
Starting from this simple physical water-barrier model of occlusion,
many authors devised equally simple tests to rank lipids and formulations [2227]. The general principle of an occlusivity measurement method is to determine the rate of evaporation from a
water-saturated closed compartment through a membrane upon
which a standardized amount of lipid or formulation is placed. The
rate of evaporation is typically determined gravimetrically or with
a transepidermal water-loss measuring tool.
From such a simple test, it appeared already decades ago that
different emollient oils exhibit different occlusive effects. Neat semisolid petrolatum always seems to come out on top of the occlusivity
ranking. However, as soon as other lipids are admixed to it, the
effectiveness of stopping water vapour transmission drops. Other
than a speculative judgment on the molecular packing density (or
porosity) in the oil film, there does not seem to be an apparent
structural chemistry logic in the ranking. Nor is the ranking order
the same in different studies: choice of membrane, emollient
concentration and detection method seem to introduce artefacts
[28, 29].
Although Wiechers recognized the existence of occlusivity as a
moisture-control mechanism, he did not pursue this simple in vitro
methodology as an emollient ranking strategy. Instead, he chose to
measure effects in vivo [30, 31].
Because of the novel and unusual approach, the size and cost of
this multi-year project, Wiechers paid great attention to the experimental detail of the testing methodology, its repeatability and statistical interpretation.
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A Moisturization
Relative performance (%)
120
Y
Measurements
100
W
V
U
S
80
Q
P
O
N
M
60
L
K
J
I
H
G
40
F
E
D
C
B
A
20
0
B Elasticity
Relative performance (%)
100
80
V
U
60
Q
P
O
N
M
40
L
K
J
I
H
G
F
20
E
D
C
B
A
C Substantivity
Relative performance (%)
120
AA
100
Z
Y
80
N
W
L
U
60
J
S
I
R
H
Q
G
P
F
E
40
D
C
B
20
Figure 1 Emollients ranked by their relative moisturization (a; 6-h reading), elasticity (b; 6-h reading) and substantivity (c; 1-h reading) performance. Arrows indicate statistical differences (P < 0.05) between individual
products.
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X-loadings
-Y
PC3
0.8
0.6
Ln(Substantivity)
0.4
Moisturisation
0.2
PC2
0
0.2
Occlusivity
0.4
0.4
0.2
0
0.2
0.4
0.6
0.8
PC1
0.4
0.2
0.2
0.4
0.6
0.8
Figure 2 Principal component analysis of moisturization (M-RP%), occlusivity and substantivity (S-RP%) data. Occlusivity data were obtained by testing emollients by the method described by de Vringer [32]. M, S and O vectors are nearly orthogonal indicating no correlation exists.
Isostearate (ISIS), which had been found to be a very poor moisturizer by the Corneometer measuring method [45], see Fig. 3.
Contrary to corneometry, near infra-red spectroscopy (NIR) can
take a direct look at the presence of water, albeit over a much
greater (1020 times) depth down into the dermis [46]. With NIR,
no water-content difference was observed between IPIS and ISIS,
indicating that the cause for the moisturizing difference between
IPIS and ISIS had to be sought much nearer to the skin surface
(Fig. 4).
Together with Bouwstra, the moisturizing effect of the selected
emollients was examined at cellular level [4749]. The distribution
of water in cross-sections of isolated skin could be visualized indirectly with cryo-scanning electron microscopy: zones with different
water content in swollen and flat layers are visible as contrast densities (see Fig. 5). The number of cell layers in the swollen and
non-swollen regions could be counted. The swollen region in the
cryo-SEM picture coincides with the NMF-rich (natural moisturizing factor) region of the SC.
In contrast to the oils, it was found that glycerine permeates easily through all layers of the SC and it creates a large region of
swollen corneocytes, an indication of more water being present in
the skin. Applying emollients does not increase the total amount of
water but can change the water gradient in the skin. Applied ISIS
and petrolatum showed a smaller upper non-swollen region than
IPIS, which was interpreted as a greater water content closer to
the skin surface, in contrast to the Corneometer findings.
Then, an even closer look at molecular organization of the skin
moisture barrier lipids was taken.
The layered lamellar phases in the SC consist of a mix of ceramides CER, cholesterols CHOL and free fatty acids FFA.
Two structural dimensions of this layered lipid phase need considering: a cross-sectional and a planar.
In cross-section, the sandwich model has gained wide acceptance [50]. Lamellar liquid bilayers in healthy human SC show a
dual periodicity: a short periodicity phase with a repeat distance of
approximately 6 nm and a long periodicity phase LPP with a
repeat distance of about 13 nm. Very long-chain ceramides (CER
EO types) are key to this LPP. In the centre of the LPP, a fluid
domain can be observed. It is also known that the quality of the
Figure 3 Isopropyl isostearate (IPIS) and Isostearyl Isostearate (ISIS) compared on the scale of corneometer relative moisturization performance.
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0.002
Abs
0.001
Difference
0.001
0.002
0.003
IPIS
1650
1700
1750
1800
1850
1900
1950
2000
0.002
Abs
0.001
Difference
0.001
0.002
0.003
ISIS
1650
1700
1750
1800
1850
1900
1950
2000
Wavelength nm
Figure 4 Near infra-red spectroscopy (NIR) spectra of untreated skin and isopropyl isostearate (IPIS)-treated skin as well as a difference spectrum (top figure)
and of untreated skin, Isostearyl Isostearate (ISIS)-treated skin as well as a difference spectrum (bottom figure). Note that IPIS and ISIS can hardly be distinguished; their moisturization signal is effectively the same.
and scissoring vibrations. Below 32C, the packed lipid chains are
visible as the doublet of an orthorhombic phase and above that
temperature as the singlet of a hexagonal phase. To separate the
IR absorption signals of skin lipids from those of the applied test
lipid emollient, perdeuterated emollients, that is, d-IPIS and d-ISIS,
had to be prepared.
An in vitro experiment with a CER : CHOL : FFA : emollient in a
1:1:1:0.75 molar ratio mixture showed a clear increase in
orthorhombic packing with both IPIS and ISIS, persisting well
above 32C (Fig. 7).
Such moisturizing mechanism of barrier improvement to a denser
lipid packing had not been shown before and can be considered as a
new mechanism in addition to occlusion, with petrolatum as best
performer, and humectancy, with glycerine as industry reference.
Wiechers called it the internal occlusion mechanism [53, 54].
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Low hydration
High
hydration
Viable
epidermis
Figure 7 Fourier transform infra-red (FTIR) spectra at 32C with a ceramides (CER) : cholesterols (CHOL) : free fatty acids (FFA) (control) and
CER : CHOL : FFA + 20% isopropyl isostearate (IPIS) or Isostearyl Isostearate (ISIS) mixtures. In presence of the emollients, the characteristic orthorhombic phase doublet is still visible suggesting they induce an increased
orthorhombic lipid packing.
Figure 6 From Ref [53]: Schematic representation of the skin lipid packing:
(a) In the liquid crystalline (La or fluid) phase, the lipids display lateral and
rotational movements. In the hexagonal (Lb or gel) phase and the orthorhombic (crystalline) phase, the lateral movements are reduced. (b) The circles represent the acyl chains of the lipids. In the liquid phase, their position
is not well defined in contrast to the hexagonal and orthorhombic packing.
In the hexagonal packing, the hydrocarbon chains can freely rotate around
their axes. In the orthorhombic packing, the lipids are in a solid state and
are packed more closely in one direction indicated by the 0.37 nm spacing.
The orthorhombic packing is considered the least permeable structure,
whereas the liquid crystalline phase is highly permeable to compounds [52].
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time interval after removal of the occluding patch, the total waterholding capacity of the skin can be determined by the amount of
water accumulated behind the patch. If less water is lost through the
skin, then it is reasonable to assume a more robust SC barrier is present. By this POST method, the more performing barrier-reinforcing
emollient could effectively be identified by Pennick et al. [58].
Surprisingly, IPIS was shown to have no benefit reducing skin
surface water loss as TEWL readings after 24 hours of occlusion were
the same as the untreated site (Fig. 8). Petrolatum fared slightly better than IPIS but the best performer was ISIS, which reduced skin
surface water loss significantly compared with both petrolatum and
IPIS, P < 0.01 and P < 0.001, respectively. Albeit less distinctly, this
was still shown to be the case when the application dose was lowered, even down to 0.25 mg cm2 (three repeat applications over
3 days under occlusion).
This time only comparing ISIS to petrolatum, the in vivo performance difference with neat emollients was also confirmed in an
11-panellist 7-day application study applying a 10% O/W formulation; the POST method was applied on day 6 of the study and the
AUC determined on day 7 [59]. The AUC values of ISIS-treated
skin areas were significantly lower than the control or petrolatum,
which did not differ.
References
1. Wiechers, J.W. and Wortel, V.A.L. Creating
effective claim support packages. Cosm. Toilet. 114, 5157 (1999).
2. Wiechers, J.W. Mind over matter: cosmetic
claim substantiation issues facing the future.
Cosm. Toilet. 120, 5764 (2005).
508
5. Wortel, V.A.L. and Wiechers, J.W. Skin sensory performance of individual personal care
ingredients and marketed personal care product. Food Qual. Prefer. 11, 121127 (2000).
6. Wiechers, J.W. and Wortel, V.A.L. Bridging
the language gap between cosmetic formulators and consumers. Cosm. Toilet. 115, 33
41 (2000).
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to Skin Barrier Function. PhD Thesis, University Leiden, The Netherlands (2011).
52. Pilgram, G.S.K., Vissers, D.C.J., van der
Meulen, H., Pavel, S., Lavrijsen, S.P.M.,
Bouwstra, J.A. and Koerten, H.K. Aberrant
lipid organization in SC of patients with atopic dermatitis and lamellar ichthyosis.
J. Invest. Dermatol. 117, 710717 (2001).
53. Wiechers, J.W., Dederen, J.C. and Rawlings,
A.V. Moisturization mechanisms: internal
occlusion by orthorhombic lipid phase
stabilisers a novel mechanism of action in
Skin Moisturization. see reference 20,
Chapter 19, 309333 (2009).
54. Wiechers, J.W. Orthorhombic phase stabilization: a new mechanism for skin moisturization. Cosm. Toilet. 124, 4550 (2009).
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