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Enhanced efficacy and sensory properties of an anti-dandruff shampoo containing zinc pyrithione and climbazole


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Dandruff is a common complaint and is suffered by as much as half of the population at some time post puberty. The condition is characterized by the presence of flakes on the scalp and in the hair, and is often accompanied by itch. The most common treatment for dandruff is the use of shampoo formulations that contain fungistatic agents such as zinc pyrithione (ZPT) and octopirox. Whilst most antidandruff shampoos are effective in resolving the symptoms of dandruff these shampoos can often result in hair condition that is less than acceptable to consumers which can lead to a tendency for them to revert to use of a non-antidandruff shampoo. This can result in a rapid return of dandruff symptoms. The aim of this investigation was to study the impact of using a combination of antidandruff actives and silicones on the resolution of dandruff and to deliver superior sensory properties to the hair. We have demonstrated that shampoo containing the dual active system of ZPT/Climbazole deposits both active agents onto a model skin surface (VitroSkin) and reduces Malassezia furfur regrowth in vitro. Clinical evaluation of the dual active shampoo demonstrated superior efficacy and retained superiority during a regression phase where all subjects reverted to using a non-antidandruff shampoo. We have also demonstrated that it is possible to deposit silicone materials from antidandruff shampoo uniformly over both virgin and damaged hair fibres that results in smoother hair fibres (as evidenced by reduced dry friction). This combination of antidandruff agents and conditioning silicones delivered from a shampoo provides subjects with superior antidandruff efficacy and desired end sensory benefits ensuring compliance and longer term dandruff removal.
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Enhanced efficacy and sensory properties of an anti-dandruff
shampoo containing zinc pyrithione and climbazole
G. A. Turner*, J. R. Matheson*, G.-Z. Li
, X.-Q. Fei
, D. Zhu
and F. L. Baines*
*Unilever Research & Development Port Sunlight, Quarry Road East, Bebington Merseyside, CH63 3JW, U.K. and
Unilever Research & Development
Centre Shanghai, 66 Linxin Road, Linkong Economic Development Zone, Changning District Shanghai, 200335, China
Received 23 July 2012, Accepted 07 September 2012
Keywords: breakage, dandruff, hair, Malassezia, scalp
Dandruff is a common complaint and is suffered by as much as half
of the population at some time post puberty. The condition is char-
acterized by the presence of flakes on the scalp and in the hair,
and is often accompanied by itch. The most common treatment for
dandruff is the use of shampoo formulations that contain fungi-
static agents such as zinc pyrithione (ZPT) and octopirox. Whilst
most antidandruff shampoos are effective in resolving the symp-
toms of dandruff these shampoos can often result in hair condition
that is less than acceptable to consumers which can lead to a ten-
dency for them to revert to use of a non-antidandruff shampoo.
This can result in a rapid return of dandruff symptoms.
The aim of this investigation was to study the impact of using a
combination of antidandruff actives and silicones on the resolution
of dandruff and to deliver superior sensory properties to the hair.
We have demonstrated that shampoo containing the dual active
system of ZPT/Climbazole deposits both active agents onto a model
skin surface (VitroSkin) and reduces Malassezia furfur regrowth in
vitro. Clinical evaluation of the dual active shampoo demonstrated
superior efficacy and retained superiority during a regression phase
where all subjects reverted to using a non-antidandruff shampoo.
We have also demonstrated that it is possible to deposit silicone
materials from antidandruff shampoo uniformly over both virgin
and damaged hair fibres that results in smoother hair fibres (as evi-
denced by reduced dry friction). This combination of antidandruff
agents and conditioning silicones delivered from a shampoo pro-
vides subjects with superior antidandruff efficacy and desired end
sensory benefits ensuring compliance and longer term dandruff
Les pellicules constituent un proble
`me fre
´quent et concernent a
`s la moitie
´de la population a
`un moment post pubertaire. La
condition est caracte
´e par la pre
´sence de paillettes sur le cuir
chevelu et les cheveux, et elle est souvent accompagne
´mangeaisons. Le traitement le plus courant pour les pellicules est
l’utilisation de formulations de shampooing qui contiennent des
agents fongistatiques comme le zinc pyrithione (ZPT) et octopirox.
Alors que la plupart des shampooings antipelliculaires soient effic-
aces dans la re
´solution des sympto
ˆmes des pellicules, ces shampoo-
ings peuvent souvent entraıˆner des e
´tats des cheveux non
acceptables pour les consommateurs qui peuvent conduire a
tendance a
`revenir a
`l’utilisation d’un shampooing non-antipellicu-
laire. Cela peut entraıˆner un retour rapide des sympto
ˆmes de pelli-
cules. Le but de cette e
´tude e
´tait d’e
´tudier l’impact de l’utilisation
d’une combinaison de principes actifs antipelliculaires et silicones
sur la re
´solution de pellicules et de fournir de meilleures proprie
sensorielles pour les cheveux. Nous avons de
´qu’un sham-
pooing contenant le syste
`me dual active de ZPT/Climbazole de
les deux agents actifs sur une surface de la peau du mode
`le (Vitro-
Skin) et re
´duit la repousse de Malassezia furfur in vitro. L’e
clinique du shampooing double actif a montre
´une efficacite
eure et a conserve
´une supe
´lors d’une phase de re
`tous les sujets e
´taient revenus a
`un shampoing non-antipellicu-
laire. Nous avons e
´galement de
´qu’il est possible de de
des mate
´riaux en silicone d’un shampooing antipelliculaire unifor-
´ment sur les fibres capillaires vierges et/ou endommage
´es, ce qui
se traduit par des fibres de cheveux lisses (comme on en te
par une re
´duction du frottement a
`sec). Cette combinaison d’agents
antipelliculaires et silicones de conditionnement fournis a
d’un shampooing apporte aux utilisateurs une efficacite
laire supe
´rieure et les avantages sensoriels finaux souhaite
´s, assu-
rant l’utilisation durable et a
`long terme l’e
´limination des
Dandruff is a common complaint and is suffered by as much as half
of the population at some time post puberty [1]. The condition is
generally characterized by the presence of flakes on the scalp and
in the hair, and is often accompanied by itch. The severity of dan-
druff in the population can range from mild scale formation (simi-
lar to that of dry skin) to seborrhoeic dermatitis (SD) [24]. The
central hypothesis of the aetiology of dandruff states that the lipo-
philic yeast, Malassezia, is the causal agent. The debate about the
role of Malassezia in the formation of dandruff, and SD, has contin-
ued since the first report of the association of this species with dan-
druff in 1874 [5]. The evidence implicating Malassezia species in
formation of dandruff has been generated over a number of years.
Essentially, this comes from observations that the levels of
Correspondence: Graham A. Turner, Unilever Research & Development
Port Sunlight, Quarry Road East, Bebington, Merseyside CH63 3JW,
U.K. Tel.: +44 151 641 3705; fax: +44 151 641 1843; e-mail: graham.
Presented at the World Congress of Dermatology, Seoul 2011 and the IFSCC Conference,
Bangkok, 2011
©2012 Society of Cosmetic Scientists and the Socie
´Franc¸aise de Cosme
International Journal of Cosmetic Science,2013,35, 78–83 doi: 10.1111/ics.12007
Malassezia (especially, M. globosa and M. restricta) species are ele-
vated in dandruff, whereas the levels of other micro-organisms
remain constant. For example, McGinley et al. found that Mala-
ssezia made up 46% of the microbial flora in normal subjects, 74%
of the flora in patients with dandruff and 83% of the flora in cases
of SD [6,7]. Further support for the association of Malassezia with
the dandruff condition comes from the observation that the most
effective anti-dandruff treatments are anti-fungal agents [e.g. zinc
pyrithione (ZPT), piroctone olamine, selenium sulphide and ketoco-
nazole] and that improvement of the dandruff condition with such
ingredients is correlated with removal of the yeast [812].
Malassezia is a commensal organism that is found on healthy
scalps as well as on dandruff scalps [13]. Initially, no pathogenic
mechanism could be associated with the deterioration from a healthy
to a dandruff scalp [14]. Subsequent work has recognized a role for
lipid metabolism via lipase action from Malassezia species. More spe-
cifically, the role of oleic acid [15] as an initiator of dandruff has been
proposed [13]. These observations imply that other factors must play
a role in the development of dandruff on susceptible individuals. Mal-
assezia spp. have also been found to trigger an innate immune
response, possibly mediated by an upregulation of toll-like receptors
(TLRs), especially TLR-2. It is possible that Malassezia may induce
inflammation in the scalp to trigger dandruff symptoms by this
mechanism [16,17]. It is true to say that dandruff has a multifacto-
rial aetiology that includes Malassezia colonization, some underlying
propensity to hyperproliferation, altered corneocyte maturation pro-
cesses and a sub-clinical microinflammatory state. Furthermore, it
has been shown that clear changes to the stratum corneum lipid
composition are present in dandruff, in both their amount and
relative composition and that there are significant changes to a
range of biomarkers of inflammation, including IL-1a[18,19].
The dandruff state is also reflected in changes in the biophysical
properties of the skin (which may be directly related to the changes in
stratum corneum lipid content and ratio). For example, the transepi-
dermal water loss of dandruff scalp is higher than that of healthy scalp
[20]. This is indicative of a perturbed stratum corneum barrier. An
investigation into the alteration of scalp stratum corneum intercellular
lipid levels in response to a ZPT anti-dandruff shampoo has demon-
strated restoration in scalp intercellular lipids [21]. ZPT treatment sig-
nificantly increased levels of triglycerides, cholesterol and ceramides.
These findings complemented those of a recent study in which ZPT
was demonstrated to improve the scalp ultrastructure, normalizing
the parakeratotic nature of dandruff skin [22]. It has been stated previ-
ously that Malassezia species are associated with dandruff formation.
However, the observation that Malassezia are commensal organisms
and that most people have Malassezia on scalp but not all people have
dandruff, implies that other changes in the underlying scalp biology
may be contributing to the development of dandruff [23].
The most common treatment for dandruff is the use of shampoo
formulations that most often contain fungistatic agents. Whilst
most anti-dandruff shampoos are effective in resolving the symp-
toms of dandruff, these shampoos can often result in hair condition
that is less than acceptable to consumers [24] which, in turn, can
lead to a tendency for them to revert to a non-anti-dandruff sham-
poo. This can have the effect of a rapid return of dandruff symp-
toms. To increase compliance, anti-dandruff shampoos must be
formulated to deliver the anti-dandruff agent effectively to the scalp
whilst providing excellent hair fibre properties.
The aim of the current investigation was to study the impact of
using a combination of anti-dandruff actives on the resolution of
dandruff and to deliver superior sensory properties to the hair. The
anti-dandruff actives selected for this study comprised a combina-
tion of zinc pyrithione (1% w/w) and the anti-fungal agent, climb-
azole (0.5% w/w). Climbazole is an imidazole anti-fungal agent
that has been demonstrated to be delivered effectively from anti-
dandruff shampoos and to inhibit Malassezia growth [25,26]. The
test formulations were further enhanced using a unique combina-
tion of silicones to maximize sensory properties. The anti-dandruff
efficacy of this novel dual active system was compared with a com-
mercial 1% zinc pyrithione-containing shampoo.
Materials and methods
Test shampoo formulations
Three shampoo formulations were tested.
ZPT/climbazole shampoo: 1% (w/w) ZPT, 0.5% (w/w) climbaz-
ole, two silicone emulsions [Silicone 1: Dimethiconol (and) TEA-
dodecylbenzenesulfonate; Silicone 2: Dimethicone (and) C12-15
Pareth-3 (and) C12-15 Pareth-23 (and) Poloxamer 407]
ZPT shampoo: commercially available shampoo containing 1%
(w/w) ZPT, dimethicone
Standard beauty shampoo: commercially available shampoo
without anti-dandruff actives
Generation of damaged hair switches
Damaged hair switches were prepared by bleaching and dyeing
dark brown European hair switches. Bleaching solution was
prepared according to the manufacturers instructions (L’Ore
´al Pla-
tine Precision) and applied to each side of the switches using a col-
ouring brush. The switches were wrapped in aluminium foil and
left for 30 min. The switches were then rinsed under tap water and
left to dry for 1 h at 50°C. The switches were then washed in SLES
solution and dried overnight at ambient conditions. The bleached
switches were then dyed using Wella Koleston Perfect 710.
In vitro studies
Determination of silicone deposition to hair fibres
Silicone deposition from shampoo formulations was measured using
X-ray fluorescence spectroscopy (XRF) with an Axios PW 1596
spectrometer with Super Q software. Dark brown, straight European
hair switches, 3 g, (n=5) were soaked in diethyl ether for 30 min
and then swirled in 20% (w/w) hot sodium lauryl ether sulphate
1EO (SLES 1EO) to remove the ether. Diethyl ether was used as a
safe and effective method to remove residual silicone on hair
switches. The switches were then washed in SLES 1EO two further
times and allowed to dry in a fume hood for approx. 20 min. Hair
switches were placed in Petri dishes and had 540 lL water and
60 lL of test shampoo applied along the length of the switch. The
switch was then massaged for 1 min and the lather left in situ for
1 min to simulate the washing process. The treated switches were
then rinsed for 30 s with tap water (3 L min
). The switches were
allowed to dry in ambient conditions overnight. Five replicates were
prepared for each sample to be tested. Hair switches were divided
into thirds to represent tip, middle and root prior to XRF analysis.
Treated hair switch segments were placed in the XRF cups in a par-
allel manner and secured in the cup. Output from the XRF spec-
trometer (count rate) was converted to concentration of silicon
with reference to a standard curve. Data were analysed using one
©2012 Society of Cosmetic Scientists and the Socie
´Franc¸aise de Cosme
International Journal of Cosmetic Science,35, 78–83 79
Antidandruff shampoo containing ZPT and climbazole G. A. Turner et al.
way ANOVA, a result was considered to be statistically significant if
the P-value for the F-test was <0.05.
Determination of zinc deposition to VitroSkin
The sheet VitroSkin
was divided into 5 95 cm pieces and
placed over one side of the smaller diameter XRF ring, with the
rough topography facing downwards. The larger ring was then
placed onto the smaller ring and pressed firmly to ensure a good
seal, ensuring that the rough topography of the artificial skin was
inside the cups. Distilled water (1.5 mL) and shampoo (0.5 mL)
were pipetted into the XRF plastic cup and mixed onto the surface
of the artificial skin using the stirring rod for 30 s (the surface of
the stirring rod remaining in contact with the surface of the artifi-
cial skin). The shampoo solution was then removed using a plastic
pipette and a rinse phase simulated using 2 mL of distilled water
and a 30 s application time. Finally, all rinse water was removed
using a pipette, and the XRF cups were allowed to dry overnight in
ambient conditions. Output from the XRF spectrometer (count rate)
was converted to concentration of zinc with reference to a standard
curve. Data were analysed using one way ANOVA, a result was
considered to be statistically significant if the P-value for the F-test
was <0.05.
Determination of fungistatic activity
Fungistatic activity of the shampoo formulations was assessed by
inoculation of Malassezia furfur onto VitroSkin that had been trea-
ted with shampoo in XRF cups in a manner similar to that
described for assessment of zinc deposition. This is an attempt to
gauge fungistatic activity on a surface following a wash and rinse
procedure simulating a typical shampoo treatment. Malassezia fur-
fur is commonly used as a model fungal species rather than using
M.restricta or M.globosa as it is relatively easy to grow in culture
on a VitroSkin surface. After allowing the treated XRF cells to dry
overnight, the samples were placed into jars containing Modified
Dixon agar. 200 lL of a suspension of M. furfur CB 1878
cells mL
) was inoculated onto the surface of the
substrate and incubated for 24 h at 32°C. After this period of
incubation, the cells were harvested with buffer solution and
100 lL of a 10-fold dilution spread onto replicate Modified Dixon
Agar plates and incubated for 34 days at 32°C. Data were
analysed using one way ANOVA; a result was considered to be sta-
tistically significant if the P-value for the F-test was <0.05.
Assessment of hair smoothness
Hair smoothness was measured using a Texture Analyser (TA.XT.
Plus Stable Microsystems. Godalming, Surrey, U.K.). Hair switches
(3 g; 16 cm 94 cm) were secured in an aluminium frame and
cleaned under tap water (37°C) at a flow rate of 4 L min
, for
5 s. 14% (w/w) sodium lauryl ether sulphate (2EO) (1.25 g) was
applied to each of the switches and agitated for 30 s and then
rinsed for 30 s under tap water. This wash cycle was repeated and
each switch combed through to align the fibres. Following this pre-
treatment, the switches were treated with the treatment shampoo
formulations using the same application protocol and tested after
overnight drying (22°C, 50% RH). Smoothness of the hair switches
was measured on the Texture Analyser by moving a probe for a
total distance of 80 mm (2 940 mm) at 10 mm s
and 500 g
load. The area of each friction hysteresis loop was calculated and
reported as Five switches were measured for each wash
treatment. Data were analysed using Student’s t-test. Results were
considered to be significant at the 95% confidence level.
In vivo studies
Anti-dandruff efficacy study design
The study was carried out in Bangkok, Thailand at the Unilever
internal facility and was a double-blind, randomized, half-head
design. The study was cleared by the Joint Research Ethics Com-
mittees, Bangkok, and all subjects gave their informed consent to
participate. Men with dandruff were recruited and put onto a
4 week run-in phase where they used a beauty shampoo at home.
Those men who still had dandruff at the end of the run-in phase
continued onto the test phase of the study (n=69). Subjects had
their hair washed three times per week in a salon using a half-
head procedure where half the head was washed with ZPT/climb-
azole shampoo and the other half was washed with ZPT-only
shampoo. The side of head treated with each product was ran-
domly allocated. Treatment continued for 4 weeks after which time
subjects returned to use of a beauty shampoo at home for a further
2 weeks (regression phase). Sixty subjects completed the test phase
of the study and 58 completed the regression phase. Dandruff was
measured using the Unilever Total Weighted Head Score (TWHS)
system [18] at baseline and at weekly intervals over the study.
TWHS was assessed 48 hours after the final application of sham-
poo. The mean TWHS adhered flake (AF) score for each subject/
treatment was used as a summary measure of treatment perfor-
mance during the test phase and during the regression phase. The
mean TWHS AF was only calculated for subjects with complete
data. Analysis of covariance was used to analyse the mean test
phase data and the mean regression phase data. Baseline measure-
ment was treated as a covariate, treatment as a fixed effect and
subject as a random effect. Results were considered to be significant
if the F-test P-value was <0.05.
Results and discussion
Anti-dandruff active deposition
Table I shows the results of the deposition studies from zinc pyrithi-
one/climbazole shampoo and zinc pyrithione shampoo. Both actives
were readily detected on the VitroSkin
after the simulated wash
protocol. The zinc pyrithione/climbazole shampoo deposited signifi-
cantly more zinc than the ZPT shampoo (P<0.05).
In vitro inhibition of Malassezia
Inhibition of the growth of Malassezia furfur by the two zinc pyrithi-
one-containing shampoos is presented in Fig. 1. The data are pre-
sented as log Malassezia number reduction. It can be seen that the
zinc pyrithione/climbazole formulation was significantly more effec-
Table I Zinc and climbazole deposition to VitroSkin
Zinc (lgcm
Mean ±SD
Climbazole (lgcm
Mean ±SD
ZPT/Climbazole 14.83 ±1.81 3.17 ±0.41
ZPT 11.10 ±1.59 ND
ND, not detected; ZPT, zinc pyrithione.
©2012 Society of Cosmetic Scientists and the Socie
´Franc¸aise de Cosme
International Journal of Cosmetic Science,35, 78–8380
Antidandruff shampoo containing ZPT and climbazole G. A. Turner et al.
tive at inhibiting growth of Malassezia furfur than the ZPT shampoo
Anti-dandruff efficacy
The results of the anti-dandruff study are presented in Fig. 2. Zinc
pyrithione/climbazole shampoo was significantly more effective
than the ZPT shampoo at reducing the clinically observed dandruff
flakes over the 4 week test phase (95% CI 3.3 to 0.8,
P<0.002). During the regression phase, the zinc pyrithione/climb-
azole shampoo retained its anti-dandruff superiority over the ZPT
shampoo (95% CI 7.4 to 4.1, P<0.001).
Silicone deposition
Silicone deposition onto virgin and damaged hair is presented in
Table II. The ZPT/climbazole shampoo, containing two silicone
ingredients [Silicone 1: Dimethiconol (and) TEA-dodecylbenzene-
sulfonate; silicone 2: Dimethicone (and) C12-15 Pareth-3 (and)
C12-15 Pareth-23 (and) Poloxamer 407] was found to deposit sig-
nificant levels of silicone onto the whole of the hair fibre (root, mid-
dle and tip) when compared to a Standard shampoo (free from
anti-dandruff actives but containing silicone) on both virgin hair
and damaged hair. The level of deposition of silicone was signifi-
cantly higher from the ZPT/climbazole shampoo than from the
Standard shampoo (P<0.05). No silicone deposition was detected
from the Standard shampoo onto damaged hair, whereas silicone
deposition was observed along all parts of the hair fibre from the
ZPT/climbazole shampoo. The level of silicone deposition onto dam-
aged hair was much lower than that measured on virgin hair.
Hair smoothness
Hair smoothness was assessed using a measure of the dry friction
force following treatment with shampoo. The results are presented
in Fig. 3. The ZPT/climbazole shampoo was found to generate sig-
nificantly lower dry frictional force than the Standard shampoo
(P<0.05) on both virgin and damaged hair.
Dandruff is a common cosmetic complaint that afflicts many people
at some point in their life. There are many shampoos available, in
both supermarkets and pharmacies, to combat dandruff using cos-
metic ingredients (for the majority of the world) or active ingredients
Figure 1 Malassezia inhibition on VitroSkin (mean ±SD, P<0.05) zinc
pyrithione (ZPT)/climbazole shampoo showed a significant inhibition of
growth of Malassezia furfur in this test and in repeat studies, P<0.05, when
compared to the ZPT shampoo.
TWHS AF (Means ± 95% CI)
Active phase Regression phase
Figure 2 Antidandruff efficacy through active and regression phase. Dual
active formulation (ZPT/climbazole) showed superior antidandruff efficacy
compared to ZPT-only shampoo over the 4 week test period and over the
2 week regression phase.
Table II Silicone deposition to virgin and damaged hair as determined by X-ray fluorescence
Silicone deposition, lgg
(mean ±SD)
Virgin hair Damaged hair
Root Middle Tip Root Middle Tip
ZPT/Climbazole 2888 ±463 1755 ±310 1766 ±65 437 ±109 428 ±52 337 ±23
Standard shampoo (No AD active) 2025 ±688 1481 ±317 852 ±464 ND ND ND
ND, not detected.
©2012 Society of Cosmetic Scientists and the Socie
´Franc¸aise de Cosme
International Journal of Cosmetic Science,35, 78–83 81
Antidandruff shampoo containing ZPT and climbazole G. A. Turner et al.
supported by the FDA Monograph in the United States (where anti-
dandruff shampoos are considered to be drugs). The most common
ingredient for treatment of the dandruff condition is ZPT. This fun-
gistatic agent controls dandruff by limiting the regrowth of Mala-
ssezia species that have been strongly implicated in the aetiology of
the condition. Despite its proven efficacy, the sensory properties of
ZPT-based anti-dandruff shampoos leave much to be desired. The
primary aim of many cosmetic shampoos is to clean the hair and
allow the subject to generate their preferred hair style with the rel-
evant sensory cues (such as conditioned benefit, control of fibre
damage, fragrance.) [24]. In the case of ZPT-based anti-dandruff
shampoos, there is a subject-perceived deficiency in the cosmetic/
sensory performance. This perceived deficiency leads to subjects
switching from an anti-dandruff shampoo to a standard shampoo
in the belief that they will achieve superior cosmetic end benefits.
Consequently, the dandruff condition will recur within a short per-
iod of time. The present investigations have been carried out to
identify a formulation that provides both enhanced anti-dandruff
efficacy and no loss in sensory and cosmetic properties on the hair.
Such a formulation will prove invaluable in the prolonged control
of dandruff as subject compliance with product use instructions will
be enhanced.
A pre-requisite of any anti-dandruff formulation is to ensure that
the active ingredient is: (i) deposited onto the scalp surface from a
shampoo; (ii) reduces growth of the Malassezia species.
In the present research, we have demonstrated that the dual
active system of ZPT/climbazole deposits both active agents onto a
model skin surface (VitroSkin). Furthermore, the deposited ingredi-
ents also reduce Malassezia furfur regrowth. Taken together the
deposition data and Malassezia inhibition data allow us to screen a
formulation before moving onto an in vivo clinical study on human
subjects. Clinical evaluation of the dual active system in the present
study demonstrated that this novel anti-dandruff combination
(ZPT/climbazole) is significantly better that ZPT-alone in reducing
dandruff on the human scalp when delivered from shampoo formu-
lations. The dual active system not only reduces dandruff flakes in
the test phase but retains the superiority during a regression phase
when subjects revert to using a non-anti-dandruff shampoo.
The sensory and fibre care properties of anti-dandruff shampoos
are essential to ensure that subjects comply with usage instructions
and continue to use the product to remove dandruff. By careful
selection of conditioning ingredients (e.g. silicones), it is possible to
achieve the aim of anti-dandruff efficacy and hair sensory benefits.
We have been able to demonstrate that by selecting the correct
combination of silicones, it is possible to coat uniformly over both
virgin and damaged hair fibres. This is not achieved by the com-
monly used silicones in “beauty” shampoos (i.e. non-anti-dandruff
shampoos) as exemplified by the Standard shampoo in the present
investigation. This in turn results in smoother hair fibres (as evi-
denced by reduced dry friction), which drives consumer compli-
ance. This combination of anti-dandruff agents and conditioning
silicones provides subjects with anti-dandruff efficacy and desired
end hair sensory benefits ensuring compliance and longer term
remission from dandruff.
The authors wish to thank Nittaya Srisuwankul and team for
running the anti-dandruff study. This work was totally funded by
Unilever Plc.
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40 000
60 000
Virgin hair
Damaged hair
20 000
ZPT/Climbazole ZPT
Dry friction force (
Figure 3 Dry friction force on switches treated with antidandruff shampoos
(mean ±SEM, *P<0.05) Dry friction force for the ZPT/climbazole shampoo
was lower than that found with the shampoo containing ZPT alone. This
result was significantly significant on damaged hair but not on virgin hair.
©2012 Society of Cosmetic Scientists and the Socie
´Franc¸aise de Cosme
International Journal of Cosmetic Science,35, 78–8382
Antidandruff shampoo containing ZPT and climbazole G. A. Turner et al.
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©2012 Society of Cosmetic Scientists and the Socie
´Franc¸aise de Cosme
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Antidandruff shampoo containing ZPT and climbazole G. A. Turner et al.
... While ZnPT is the most common primary active for treating dandruff, shampoos are often formulated with secondary actives, such as keratolytic agents [117], other anti-fungals [114,118], and antiinflammatories [119,120] to achieve complimentary action, especially S.E. Mangion et al. useful in more moderate-severe disease. ...
... In particular, keratolytic agents such as salicylic acid can be incorporated to aid in flake removal through reduction of skin hyperproliferation rather than by directly targeting yeast. To illustrate the beneficial attributes of a dual anti-microbial shampoo, a study was performed by Turner et al. [118] which demonstrated improved topical delivery, inhibition of Malassezia yeast growth, and anti-flaking efficacy for a 1 % w/v ZnPT shampoo combined with the secondary anti-fungal climbazole (0.5 % w/v), however it is not known whether the improved efficacy is due to enhanced deposition of primary active, or whether it is due to an additive effect of climbazole alone. ...
... Other actives used in combination with ZnPT can be derived from natural products, however it should also be recognised that botanicals can require higher concentrations for effect and care should be taken to avoid any adverse reactions [121]. A formula with beta-glycyrrhetinic acid, an anti-inflammatory agent isolated from liquorice root, combined with ZnPT and cyclopiroxalmine (secondary anti-fungal) was found to significantly reduce skin flaking, itching, and biomarkers of inflammation in seborrheic dermatitis [118]. In a separate study betaglycyrrhetinic acid at 6 % concentration was found to reduce Malassezia scalp levels [122]. ...
Seborrheic dermatitis (SD) is a common dermatological disorder with symptoms that include skin flaking, erythema and pruritus. This review discusses the topical products available for treating SD, which target several aspects of disease pathobiology, including cutaneous microbial dysbiosis (driven by Malassezia yeast), inflammation, sebum production and skin barrier disruption. Among the various treatments available, zinc pyrithione (ZnPT) based products that exhibit anti-fungal action are the market leaders. A skin compartment approach is presented here for combining ZnPT exposure information with threshold levels for anti-fungal efficacy and toxicity, overall providing a comprehensive picture of ZnPT therapeutics and safety. While Malassezia yeast on the surface are effectively targeted, yeast residing beyond the superficial follicle may not receive adequate ZnPT for anti-fungal effect and may continue to grow, forming the basis for skin re-colonisation. Levels entering systemic circulation from topical delivery are well below toxic thresholds, however the elevated zinc levels within the viable epidermis warrants further investigation. Strategies to improve formulation design can be broadly classified as influencing 1) topical delivery, 2) therapeutic bioactivity, 3) skin mildness, and 4) sensory attributes. Successful SD treatment ultimately requires formulations that can balance efficacy, safety, and consumer appeal.
... The aetiology of dandruff is multifactorial, but includes sebaceous lipids, Malassezia yeast and individual susceptibility [4]. Currently, the most common treatment for dandruff is regular use of antidandruff (AD) shampoos that contain fungistatic agents, such as zinc pyrithione (ZnPT) and climbazole, or a potentiated ZnPT, which have shown significant efficacy on the resolution of dandruff [5][6][7][8]. The efficacy of AD shampoos is always assessed by measuring scalp flaking, the most important dandruff symptom, within a doubleblind, randomized controlled clinical trial. ...
... b. Split-head paired design, with just one group of subjects to compare 2 test shampoos, where the left and right sides of the head are each washed separately with a different shampoo, by trained study staff at a study site [7,13]. ...
... The scalp visual grading of dandruff conditions by expert assessors with the TWHS method has been implemented successfully and manifested scientifically in several clinical trials published to evaluate the anti-flaking efficacy of anti-dandruff shampoos [7,13,16] and was used in the present study at baseline and weekly dandruff assessment during the four-week treatment phase. ...
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Objective Dandruff is a common scalp condition that can be improved by regular use of shampoos containing anti-fungal actives. The efficacy of anti-dandruff shampoos can be assessed by measuring scalp flaking, one of the important dandruff symptoms. A randomized, double-blind trial is often used with one of two clinical designs: whole-head parallel design and split-head paired design. We aimed to explore the difference in product differentiation between these two designs using the same two test shampoos and the same scalp flaking assessment method (Total Weighted Head Score Adhered Flakes – TWHS AF). Methods A clinical study was conducted with a 2-3 weeks wash-out phase and a 4-week test phase, consisting of 2 cells: 120 subjects with whole-head parallel design, divided into 2 subgroups (1:1) using on-site controlled washing method (either wash their own hair at a study site, under the instruction of a study supervisor or wash their own hair at home, as per instructions, but without supervision) and 35 subjects with split-head paired design using salon-staff washing method. Both cells employed hair washing at frequency of three times a week, and TWHS AF measurement once a week from the baseline assessment. Results Both designs gave similar differences in TWHS AF between products: 5.6 units (95% CI: 4.1 to 7.0 units) in whole-head design and 5.9 units (95% CI: 4.9 to 6.9 units) in split-head Design. Conclusion Split-head paired design shows a similar ability of detecting product difference as whole-head parallel design, whereas it is a choice of more efficient and more cost-effective, as only a quarter of the subjects are required to demonstrate the efficacy between anti-dandruff shampoos.
... Imaging studies provide spatial information and topical application, however rarely can provide accurate quantitative data on delivery amounts. Quantification of dose can be performed with a range of chromatography, spectroscopy and radiolabeling methods highlighted in Table 2 [12,115,128,130,[141][142][143][144]. An important consideration for formulation optimization is that the same quantitative approach must be followed when comparing delivery between formulations, as each analysis method will have different levels of accuracy and precision. ...
... Studies using human keratinocytes demonstrate very high sensitivity to ZnPT (TD 50 = 500 nM) at concentrations which are 100,000-fold lower than the 2% maximum level currently approved in shampoo [164]. Data from ex vivo static diffusion cell experiments reveal that viable epidermis and dermis may be exposed to ZnPT levels within this range (0.75 µg/cm 2 for human skin) after topical exposure (Table 3) [12,115,128,[141][142][143]145]. It should be noted however that this is based on results from Franz cell studies using [ 14 C] ZnPT, which, as a radiolabel for the organic moiety, may not fully predict the levels of Zn 2+ implicated in inducing cytotoxicity. ...
Full-text available
Zinc pyrithione (ZnPT) is an anti-fungal drug delivered as a microparticle to skin epithelia. It is one of the most widely used ingredients worldwide in medicated shampoo for treating dandruff and seborrheic dermatitis (SD), a disorder with symptoms that include skin flaking, erythema and pruritus. SD is a multi-factorial disease driven by microbiol dysbiosis, primarily involving Malassezia yeast. Anti-fungal activity of ZnPT depends on the cutaneous availability of bioactive monomeric molecular species, occurring upon particle dissolution. The success of ZnPT as a topical therapeutic is underscored by the way it balances treatment efficacy with formulation safety. This review demonstrates how ZnPT achieves this balance, by integrating the current understanding of SD pathogenesis with an up-to-date analysis of ZnPT pharmacology, therapeutics and toxicology. ZnPT has anti-fungal activity with an average in vitro minimum inhibitory concentration of 10–15 ppm against the most abundant scalp skin Malassezia species (Malassezia globosa and Malassezia restrica). Efficacy is dependent on the targeted delivery of ZnPT to the skin sites where these yeasts reside, including the scalp surface and hair follicle infundibulum. Imaging and quantitative analysis tools have been fundamental for critically evaluating the therapeutic performance and safety of topical ZnPT formulations. Toxicologic investigations have focused on understanding the risk of local and systemic adverse effects following exposure from percutaneous penetration. Future research is expected to yield further advances in ZnPT formulations for SD and also include re-purposing towards a range of other dermatologic applications, which is likely to have significant clinical impact.
... According to the latest report released by the U.S. market research firm Transparency Market Research, the market scale of global hair products in 2015 was 81.3 billion USD, and it is expected to reach 105.3 billion USD by 2024. Ingredients in hair products can be adsorbed on the surface of hair or penetrate into hair through permeation and absorption to meet consumers' many daily hair-care needs, such as cleaning, repair, coloring, and styling [8][9][10][11][12]. Studies have shown that hair, as a natural keratin adsorbent, can be used to remove organic pollutants, such as formaldehyde [13][14][15], phenol [16], and heavy-metal ions [17], from wastewater. ...
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The permeation and absorption of solutes into human hair are highly relevant to various applications, including the formulation of hair-care products, the development of water pollution control and remediation, and the risk assessment of environmental exposure. Based on a detailed introduction of the structure and composition of hair, the effects of the properties of hair (structure, composition, and charge properties), the physicochemical properties of solutes (molecular size, shape, and hydrophobicity), and the conditions of the surrounding medium (solvent composition, temperature, and pH) on the permeation and absorption were comprehensively analyzed. Several theoretical models were reviewed, including two-part/two-state, porous media diffusion, homogeneous medium diffusion, heterogeneous medium partition, and diffusion models. Finally, future research directions for the permeation and absorption of solutes in hair were proposed to provide a foundation for the further optimization and application of permeation models.
... Scanning electron microscopy (SEM) studies found a similar pattern of distribution of the two drugs in excised human skin [79]. The differences in the distribution of the two drugs suggests that their application as a combination therapy may be beneficial and is corroborated by in vivo studies which found superior efficacy of the drugs together vs individually [80]. ...
The study of drugs at a cellular level has the capacity to provide meaningful information on drug distribution, mechanism, pharmacokinetics, and metabolism. A comprehensive understanding of drug behavior in cells represents an essential facet of drug discovery, with great time and expense spent to ensure the safety and efficacy of pharmaceutical compounds. Stimulated Raman scattering (SRS) imaging offers unique advantages over other molecular and microscopic imaging techniques, namely excellent spatiotemporal resolution and chemical specificity. SRS allows a drug to be imaged either by inherent features of its molecular structure or by attachment of a small, spectroscopically bioorthogonal Raman-active tag which resonates within the cell-silent region, precluding the requirement for bulky labels. Advances in SRS technologies have facilitated the imaging of drugs in three major categories: cancer therapeutics, dermatological drugs, and drug delivery systems. Within each of these categories, a fuller understanding of drug mechanisms, quantitative determination of drug concentration, and intracellular localization of drug compounds has allowed invaluable insight to be obtained.
Background: Dandruff is a pervasive chronic condition which negatively impacts quality of life. Effective treatment requires efficient delivery of scalp benefit agents that control commensal scalp Malassezia levels. Delivery of benefit agents from shampoos requires balancing many technical parameters to achieve the desired outcome without sacrificing secondary paraters such as cosmetic attributes. Aim: To develop formulation technologies that increase the shampoo delivery efficiency of the scalp benefit agent piroctone olamine (PO). Increased delivery should result in increased anti-dandruff efficacy. Methods: Micellar stability and association parameters were quantified via dynamic surface tension and NMR diffusion parameters, respectively. PO delivery has been assessed in vivo both on the scalp surface and follicular infindibula using extraction procedures and analytical analysis. Clinical anti-dandruff efficacy was assessed for an advanced delivery technology prototype in comparison to standard delivery technology. Results: Shampoo prototypes have been developed that increase the delivery efficiency of PO. Both surfactant- and polymer coacervate-based approaches have been developed. Decreased micellar stability results in weaker association between PO and micelles, resulting in more efficient PO retention on the scalp surface and delivery to the infundibula. Increased charge density of cationic polymers optimizes coacervation enabling improved PO delivery as well. Increased PO delivery has been shown clinically to result in higher anti-dandruff efficacy as measured by both visible flakes and underlying biomarkers. Conclusion: Increased efficiency PO delivery shampoos have been developed by optimization of both surfactant and coacervate parameters. The increased deposition efficiency results in significantly more products with significantly greater anti-dandruff efficacy.
Background The combination of flow chemistry and microreactor technology is emerging in the modern chemical industry. It can link chemical engineering, organic synthesis, and green chemistry, which provides a safety guarantee for dangerous chemical processes. Method In view of the advantages of continuous flow synthesis, a more efficient method for the synthesis of 3,5,5-trimethylhexanoyl chloride from triphosgene and 3,5,5-trimethylhexanoic acid catalyzed by N, N-dimethylformamide was obtained by using silicon carbide microreactor, which was reported for the first time. Computational fluid dynamics (CFD) simulation of single-phase flow in an advanced microreactor was carried out with OpenFOAM software. The flow lines, lag zone, velocity distribution, pressure field, and residence time distribution (RTD) were obtained at different flow rates (5–100 mL/min). Significant findings A continuous flow process for the 3,5,5-trimethylhexanoyl chloride with a 91% isolated yield has been reported. Triphosgene and 3,5,5-trimethylhexanoic acid were used as starting materials to achieve excellent results in the silicon carbide flow reactor, which could tolerate the corrosion of chloride ions at 55 ℃ and 0.8 MPa. In the continuous flow process, based upon the cyclic feed reaction method, the product was obtained with sufficiently high 3,5,5-trimethylhexanoic acid conversion (> 99%) and product 3,5,5-trimethylhexanoyl chloride selectivity (95%). The throughput reached 0.35 kg/h, and the purity of the final product was greater than 90% by distillation, which was in accordance with the needs of production. This new process using more polar tetrahydrofuran as the solvent was time- and cost-effective, and the obtained product had a higher yield, brighter color, and less impurity. With the increase of the flow velocity, the stagnation area and the swirling intensity increased slightly, but the velocity and pressure distribution in each mixing unit were relatively uniform. Additionally, the reactor had symmetric RTDs at all flow rates. Due to the larger flow rate, the Peclet number was increased and the axial dispersion was reduced, with the result of a narrower RTD curve.
Deuterium labeling has been widely used for SRS metabolic imaging. It is the minimum label that causes little perturbation to the biochemical property of target molecules. In this chapter, we introduce the applications of deuterium-probed SRS metabolic imaging in living organisms. We first review recent developments of two SRS imaging techniques that enable simultaneous visualization of the metabolic dynamics of a variety of biomolecules (lipids, protein, and DNA) in living organisms. One novel technique uses D2O as the deuterium source and combines it with SRS (DO-SRS) microscopy for metabolic imaging. The other uses deuterated glucose for visualizing various newly synthesized biomolecules by spectral tracing of deuterium (STRIDE) in the living organism. Next, we overview a volumetric tissue clearing-enhanced SRS imaging technique that increases imaging depth by 10-fold. At last, we review the applications of SRS for imaging protein metabolic dynamics in mouse tissues and organs, by in vivo intracarotid injection of the deuterated amino acid (D-AA).
Cross‐over trials are trials in which patients are allocated to sequences of treatment with the purpose of studying differences between individual treatments. The main advantages of cross‐over designs are efficiency and the ability to study individual reaction to treatment. Cross‐over designs can only be used in chronic diseases. The apparent treatment effect has been halved for the simple reason that because the treatment effect is permanent, the sequence beta‐agonist – placebo yields no information about the effect at all. Carry‐over can also pose a problem for parallel‐group trials, but less plausibly so. The best approach to planning cross‐over trials is to consider carefully, in the light of pharmacokinetic and general pharmacological theories, what wash‐out period is required. The problem in practice is that of determining a suitable joint prior distribution for carry‐over and the treatment effect.
The serendipitous formation of Bandrowski’s Base, an oxidized trimer of p-phenylenediamine, a backbone molecule of the hair dye industry, in the presence of the antifungal/antidandruff agent clotrimazole, and the subsequent...
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Dandruff is characterized by a flaky, pruritic scalp and affects up to half the world's population post-puberty. The aetiology of dandruff is multifactorial, influenced by Malassezia, sebum production and individual susceptibility. The commensal yeast Malassezia is a strong contributory factor to dandruff formation, but the presence of Malassezia on healthy scalps indicates that Malassezia alone is not a sufficient cause. A healthy stratum corneum (SC) forms a protective barrier to prevent water loss and maintain hydration of the scalp. It also protects against external insults such as microorganisms, including Malassezia, and toxic materials. Severe or chronic barrier damage can impair proper hydration, leading to atypical epidermal proliferation, keratinocyte differentiation and SC maturation, which may underlie some dandruff symptoms. The depleted and disorganized structural lipids of the dandruff SC are consistent with the weakened barrier indicated by elevated transepidermal water loss. Further evidence of a weakened barrier in dandruff includes subclinical inflammation and higher susceptibility to topical irritants. We are proposing that disruption of the SC of the scalp may facilitate dandruff generation, in part by affecting susceptibility to metabolites from Malassezia. Treatment of dandruff with cosmetic products to directly improve SC integrity while providing effective antifungal activity may thus be beneficial. © 2012 Unilever PLC. ICS © 2012 Society of Cosmetic Scientists and the Société Française de Cosmétologie.
Dandruff, a scaly disorder of the scalp, is a benign affliction shared by about 45% of the human population, irrespective of sex and ethnicity. Paradoxically, some textbooks on Dermatology even ignore it.
Background and objective: Dandruff and the commensal yeasts Malassezia spp. are often conceptually bound together. However, no consistent correlation was reported between yeast numbers on lesional skin and severity of the skin condition. The aim of the study was to compare the density of Malassezia spp. with the clinical severity of dandruff before, during and after using a 1% ketoconazole shampoo every other day. Method: Twenty men suffering from dandruff were enrolled in the open study. Clinical and laboratory assessments were made at entry and at completion of the 6-week ketoconazole treatment, as well as every third day during the 1-month post- treatment follow up. Dandruff were collected using clear self-adhesive discs. Living yeasts were revealed by the neutral red stain and their numerical density was evaluated by computerized image analysis. Results: The marked inhibitory activity of ketoconazole against the yeasts was accompanied by a significant decrease in the clinical severity score of dandruff. During the post-treatment follow up, a significant power relationship was yielded between the dandruff clinical scores and the living yeast densities. Conclusions: The 1% ketoconazole shampoo formulation abates the density of the commensal Malassezia spp. on the scalp with dandruff. A correlation exists between yeast numbers on lesional skin and dandruff severity. Clinical relapse may occur with the re-emergence of Malassezia spp.
The composition of the scalp microflora was assessed quantitatively in normal individuals and in patients with dandruff and seborrheic dermatitis, disorders characterized by increasing scalin. Three organisms were constantly found: (1) Pityrosporum, (2) aerobic cocci, and (3) Corynebacterium acnes. Pitrosporum (mainly Pityrosporum ovale) made up 46% of the total microflora in normals, 74% in dandruff, and 83% in seborrheic dermatitis. The geometric mean number of organisms per cm2 in non-dandruff subjects was 5.04 105; 9.22 105 in dandruff subjects; and 6.45 105 in those with seborrheic dermatitis. The cocci were dominantly Baird-Parkertype SII and no quantitative or qualitative change occurred in the scaling disorders. C. acnes comprised 26% of the flora on the normal scalp, 6% in dandruff, and only 1% in seborrheic dermatitis. These results differ significantly from previous reports which describe a much more complex microflora and suggest an etiologic role for microorganisms in dandruff.
Thirty-two subjects who suffered from dandruff participated in a study in which one-half of the head was washed with a shampoo containing 1% zinc pyrithione (ZPT) and the other half was washed with the same shampoo without ZPT. Four groups, eight subjects per group, were shampooed one, three, six or nine times (shampoo frequency twice per week). Clinical dandruff gradings of each half of the head were made 4 days after the last shampoo in each group, when scalp biopsy samples were also taken from each half of the head. Measurements of labelling index (LI), mean epidermal thickness (MET), and assessment of the numbers of PAS- and Gram-positive micro-organisms were made on the biopsy samples. There was a progressive reduction in dandruff on the sides of the head treated with the ZPT shampoo, the differences relative to the placebo-treated areas being statistically significant after three, six and nine washes. There were no significant differences in L1 between treatment groups and the MET was shown to vary according to the treatment and the number of washes. There was a significant reduction in the number of PAS-positive micro-organisms (but not Gram-positive micro-organisms) on the ZPT-treated areas.
A scale of skin treatments is analysed, which bases on the detection of UV-generated free radicals in pig skin. Physiological and anatomical similarities between man and pig made this animal a good model for man in many research areas. The determination of the Radical Status (free radical response) offers the possibility to see in an early stage the effect of exterior and interior influences. The detection of the skin's response after a normalized radical generation by defined UV dose combined with the application of external and internal influences enables a comprehensive and easy classification of skin products and therapies. The effect of substances, especially, applied topically on the skin, like it is usual in cosmetics and pharmacy, can be classified. The relevance of the RSF method is demonstrated with the application of numerous different treatments on the skin.
Zinc pyrithione (ZPT) is the active ingredient most commonly used in many antidandruff treatments. Despite decades of successful use to treat human scalps, little is understood about the antifungal mechanism of action of ZPT. The objective of this study is to understand the molecular mechanism by which ZPT inhibits fungal growth, the underlying basis for its therapeutic activity. Modern systems biology approaches, such as deletion library screening and microarray analysis, were used in combination with traditional measures of metal content, microbial growth and enzyme assays. It was shown that ZPT inhibits fungal growth through increased cellular levels of copper, damaging iron-sulphur clusters of proteins essential for fungal metabolism. The molecular basis for the antifungal activity of the commonly used active ZPT has been elucidated, more than 50 years since its introduction, as utilizing a copper toxicity mechanism that targets critical iron-sulphur proteins.
From their original description, fungi of the genus Malassezia (previously Pityrosporum) have been associated with dandruff and seborrhoeic dermatitis. The principle evidence on which this connection was based was that the organisms were present, often in high numbers, on the skin in these conditions and that both responded to treatment that inhibited or destroyed Malassezia yeasts. The availability of new tools such as genomic and proteomic analyses has begun to provide a new insight into the pathogenetic mechanisms involved. New evidence shows the production of specific phospholipases on affected skin sites in dandruff and signalling molecules such as malassezin in seborrhoeic dermatitis. It is still not clear why those individuals and skin sites, prone to either disease, are particularly associated with the presence of these marker molecules but these studies are providing clues to the different ways in which organisms, which are normally commensals, interact with human skin.