12/20 | Volume 146 | Thannhausen, Germany, December 16, 2020

skin care
The Extracellular Metabolite of
Bacillus coagulans MTCC 5856 as the
Next Generation Cosmetic Ingredient

12
A New Peptide Mimicking a Good Sleep
in Times of Pandemia

2020
english

quality assurance
Evaluation of Health Risks Caused by

Next Generation
Microorganisms in Cosmetic Products

HLB
hair care
Dandruff Control
Alternative Concepts

trademark rights
New Forms of Trademarks – “Sensual”
Next Generation Dandruff Control
Hair That’s Fair: New Generation
of Silicone Gum Blends
Intellectual Property Rights for Cosmetics

F. Genrich, C. Koch, S. Lange, N. Bugdahn, G. Schmaus

SOFW Journal 12/20  |  Volume 146  |  Thannhausen, Germany, December 16, 2020
 personal care | scalp care

Next Generation Dandruff Control

F. Genrich, C. Koch, S. Lange, N. Bugdahn, G. Schmaus

abstract

D andruff is a global phenomenon and the need for cosmetic products to relieve symptoms like flaking, itching and redness
remains high [1]. Anti-dandruff consumer products in the cosmetics market typically rely on the use of strong anti-fungal
ingredients. Three conventional actives are commonly used from a global perspective: zinc pyrithione, climbazole and piroctone-­
olamine. Except for a limited selection of multifunctionals, some blends or natural extracts, there has been no major new active
launched to market for decades. In this article we present an entirely new solution: propanediol caprylate (Crinipan® PMC
green), a novel molecule for cosmetic applications, developed to serve multiple needs: comparable efficacy to conventional
anti-dandruff actives, natural origin, green chemistry, sustainability, new mode of action and simple formulating.

Introduction
Dandruff control can be characterized by the use of three safety of the product as well as appropriate anti-dandruff ef-
conventional ingredients: zinc pyrithione, climbazole (Crini- ficacy. In this regard manufacturers typically refer to the use
pan® AD) [2, 3] and piroctone-olamine. All three actives are of JSQI (Japanese Standards of Quasi-drug Ingredients) listed
pri­mari­ly effective against the yeast Malassezia spp. that is ingredients; one of these ingredients is o-cymen-5-ol (IPMP;
linked to dandruff formation, and all have been used in the SymOcide® C) [8]. o-Cymen-5-ol is also listed as a preser-
personal care market for decades. Even though they are typi­ vative, both in Europe (EU Cosmetics Regulation Annex V)
cal­ly not used specifically for preservation, all three estab- and Japan (Japanese Standard for Cosmetics, Appendix 3).
lished actives are part of the European Cosmetics Regulation Looking at the molecule’s physicochemical nature, its lipo-
(EC) No 1223/2009 list of preservatives allowed in cosmetic philic properties suggest that it is a suitable active for skin
products (Annex V). This is a rather historical classification re- benefits as well.
flecting the active’s anti-fungal properties that would surely For formulators, ease of handling in the process of incor-
contribute to preserve a product, but the main reason for use porating cosmetic actives into shampoos has always been a
is a result of the active’s antimicrobial properties, specifically major consideration. Liquid actives simplify the formulation
controlling Malassezia on the scalp and thus reducing dan- process significantly [2], because surfactant-based formula-
druff formation. It is not a requirement for an anti-dandruff tions are often made via cold process. Taking a look at the
agent to be part of a preservative list in terms of European established actives, none of them is liquid: Zinc pyrithione is
law. Some multifunctional ingredients are also worth men- a surfactant-insoluble system, available as a dispersion. Thus
tioning: Decylene glycol (SymClariol®), for example, is not zinc pyrithione is only found in cloudy shampoo formula-
an established active for dandruff control, though several tions, while transparent shampoos are possible solely with
reports on its positive effects for scalp care have been pub- surfactant-soluble actives such as climbazole and piroctone
lished [4, 5]. olamine. Though transparent shampoos can be made with
Globally speaking, anti-dandruff is considered a cosmet- climbazole and piroctone olamine, the pure actives are crys-
ic claim not subject to particular regulation, but there are talline solids which need to be solubilized first.
some exceptions. Two examples for more strictly regulated It is known from literature that short to medium chain fatty
markets are the US and Japan. In the US, out of the three acids also possess anti-fungal properties, but their practical
mentioned conventional actives, only zinc pyrithione is posi­ use in cosmetics is limited by their intensive smell. Surpris-
tively listed on the OTC drug monograph by the Food and ingly, a nearly identical antimicrobial effect was reported
Drug Administration (FDA) and therefore used in the North for the ester derivatives [9]. Considering the relevance of an
American market as an active [6]. In Japan, anti-dandruff anti-Malassezia effect for reducing dandruff, a completely
products are considered quasi drugs (QD) [7]. Cosmetic new ester-based anti-dandruff technology has been devel-
manufacturers owning a QD-license have to apply for a pre-­ oped [10].
market approval from the authorities before launching a new Serving the demand for new green solutions, we are pre-
consumer product. The application has to demonstrate the senting a modern, natural derived, anti-dandruff technology

8 sofwjournal | 146 | 11/20
 scalp care | personal care

8 M. globosa (CBS 7705) in medium

6
Malassezia’s
Malassezia. lipases 4

%
spp 2
0 Time [h]
Crinipan® PMC green 0 20 40 60 80
"AUTO cleavage
DOWN-REGULATION" 8 M. restricta (CBS 7877) in medium
6
4

%
CAPRYLIC ACID 2
PROPANEDIOL
0 Time [h]
0 20 40 60 80

Caprylic acid Crinipan® PMC green

Fig. 1 Suggested mechanism for propanediol caprylate´s mode of action; Presence of Malassezia spp. “activates” propanediol caprylate to
­release the active caprylic acid.

with an innovative mode of action (Fig. 1). The activity of ing from ethyl caprylate and propanediol. Finally considering
propanediol caprylate (Crinipan® PMC green) [11, 12] relies the broad variety of sustainable methods for direct esterifi-
on Malassezia’s natural dependence on triglycerides (esters) cation known today [17], a solvent-free esterification of ca-
from sebum. The new liquid molecule [13, 14] propanediol prylic acid and propanediol with even better atom economy
caprylate works due to its similar chemical ester-structure: was developed. This non-hazardous and energy efficient pro-
Malassezia’s lipases cleave the ester to release the actual cess generates only water as side product, clearly respects
active (caprylic acid) that will in turn reduce Malassezia ac- the green and sustainable chemistry principles, and leads to
tivity, leading to a reduction of dandruff. Propanediol cap- a natural origin index of 1 (ISO 16128) for Crinipan® PMC
rylate is made by green chemistry from 100% plant-based green.
feedstock.
Antimicrobial Efficacy against Malassezia

Materials & Methods An agar dilution test was performed for nine Malassezia
strains (Tab. 1) according to a procedure described by May-
Production Process ser [9]. This included typical representative strains, known for
dandruff formation on human skin (M. globosa, M. restricta).
Propanediol Caprylate is a colorless and liquid ester that can The strains were maintained on modified (m) Dixon-agar and
be derived from natural materials like palm or palm kernel testing was performed with mDixon agar including the re-
oil. Our objective was to produce propanediol caprylate using spective test materials (caprylic acid, propanediol caprylate,
the 12 principles of green chemistry [15]. For this a green control excluding antimicrobials).
process with optimal atom economy was favored, including
waste prevention, use of catalytic systems, non-hazardous Determination of Microbial Ester Cleavage
materials, and low consumption of energy. Following this
concept we first envisioned a trans-esterification [16], start- Ester cleavage of propanediol caprylate was investigated for
the human associated species M. globosa and M. restricta
(Fig. 1). A cell count of 0.5-2.5 × 105 CFU/µl was transferred
to an agar plate, overlaid by propanediol caprylate and in-
Species Strain
cubated at 32°C. After defined incubation times of 0, 3, 6,
M. furfur CBS 1878 12, 24, 48, and 72 h the supernatant was removed and the
CBS 7222, CBS 7979, ATCC 42132, concentration of propanediol caprylate and caprylic acid de-
M. sympodialis
DSM 6171 termined by gas chromatography.
M. globosa CBS 7966, PM1, CBS 7705
M. restricta CBS 7877 In vivo Study Assessing Reduction of Dandruff

Source: CBS = Centraalbureau voor Schimmelcultures, Utrecht, Nl; ATCC =

American Type Culture Collection, Manassas, USA; DSM = Deutsche Samm­ In order to assess the dandruff reduction by propanediol ca-
lung von Mikroorganismen und Zellkulturen, Braunschweig, D; The M. glo- prylate on scalp from a typical rinse-off shower formulation,
bosa wildtype strain PM1 was isolated and maintained by P. Mayser.
the product has been included in a standard clear sodium
laureth sulfate based shampoo formulation. The evaluation
Tab. 1 Malassezia test strains.
was performed comparing to both positive and negative

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 personal care | scalp care

With Pro- Ingredients

With
panediol Aqua
­Climbazole
Ingredients Placebo Caprylate
(Crinipan® Cocamidopropyl Betaine
(Crinipan®
AD) Decyl Glucoside
PMC green)
Sodium Laureth Sulfate. Sodium Cocoyl Isethionate
17 17 17
Lauryl Glycoside PEG-80 Sorbitan Laurate
Citric Acid 0.15 0.15 0.15 PEG-150 Distearate
Disodium EDTA 0.1 0.1 0.1 Glycerin
Water (Aqua) 76.55 76.05 76.05 Citric Acid
Polyquaternium-10 0.2 0.2 0.2 Sodium Benzoate
Sodium Benzoate 0.5 0.5 0.5 Sodium Methyl Cocoyl Taurate
Phenoxyethanol 0.5 0.5 0.5 Parfum
Cocoamidoproyl Betaine 5 5 5 Disodium EDTA
Anti-dandruff ingredient 0 0.5 0.5 Polyquaternium-10

Tab. 3 In vivo Shampoo Study; Conditioning Phase;

Tab. 2 In vivo shampoo study; test shampoos. Mild wash-out shampoo from the market.

controls (Tab. 2): As positive control, the established anti-­ (1:1 w/w%), the solutions were treated by applying a de-
dandruff active climbazole was added to the shampoo base. fined foam generation process. The bubble count was re-
As negative control, the shampoo base was used without corded for 20 minutes and images of the foam bubbles were
addition of an active (placebo). In terms of the dose of the taken after 500 s. Additionally, foam quality and sensorial
actives, climbazole was used at its established – known to be tests were performed by 24 untrained panelists by using a
effective – dosage of 0.5%; propanediol caprylate was used shampoo containing 1.0% propanediol caprylate vs place-
at the same level. All shampoo formulations were applied un- Figure 2 / Abb. 2
bo. After a defined prewash procedure, 100 µl of shampoo
fragranced. were applied onto the back of the hand in random order, and
The study was started after a 14 days conditioning period the panelists assessed the product’s foam volume and skin
in which the subjects were told to wash their hair only with softening effect.
a neutral shampoo (containing no actives) from the
market (Tab. 3). The test shampoo application was
performed 3 times per week, each time adhering to 2500 M. furfu r CBS 1878 M. furfu r CBS 7019 M. sympodialis CBS 7222
Figure 2 / Abb. 2
3 minutes of incubation time on scalp. M. sympodialis CBS 7979
M. globosa CBS 7966
M. sympodialis ATCC 42132
M. globosa PM1
M. sympodialis DSM 6171
M. restricta CBS 7 877
The in vivo evaluation of dandruff flaking was per- 2000
formed by dermatologists on a 1 (no dandruff) to 5
(severe dandruff) scale, directly after the conditioning 1500
phase (baseline) and after 30 days of use (30 d). Ad-
ditionally, an olfactory evaluation was done by the 1000
Malassezia
2500 subjects to investigate
M. furfu r CBS 1878 a r potential
M. furfu CBS 7019 odorM.from caprylic
sympodialis CBS 7222
M. sympodialis CBS 7979 M. sympodialis ATCC 42132 M. sympodialis DSM 6171 500 Malassezia
acid formation.
M. globosa CBS 7966 M. globosa PM1 M. restricta CBS 7 877
2000 Malassezia
0 Malassezia
Physicochemistry: Caprylic acid Caprylic acid propanol
Propanediol ester
Caprylate
1500
Effect on Foam and Sensorial Properties (Crinipan® PMC green)

Malassezia strains most relevant for dandruff formation

1000
Anti-dandruff actives are mainly used in surfactant
Malassezia furfur 2000 ppm
based formulations. For the evaluation of propane-
500 Malassezia sympodialis 1000 - 2000 ppm
diol caprylate on foam behavior, shampoo formu-
Malassezia globosa 500 – 1000 ppm
0 lations containing 0.5 and 1.0 w/w% propane-
Malassezia restricta 1000 ppm
diol caprylate
Caprylic acidwere tested. As nega­
Caprylic acidtpropanol
Propanediol ive control,
ester
Caprylate
(Crinipan® PMC green)
the shampoo base was used without addition of
active
Malassezia strains (placebo).
most relevant The
for dandruff samples were investigated at
formation Fig. 2 The MIC values for propanediol caprylate are in a similar range as for
caprylic acid. The efficacy of caprylic acid can be used for cosmetic purposes
Krüss GmbH by using the Dynamic Foam Analyzer
by applying its ester.
DFA 100. After diluting with demineralized water

10 12/20 | 146 | sofwjournal sofwjournal | 146 | 11/20 10
 scalp care | personal care
Figure 3 / Abb. 3

Significant reduction of dandruff by Crinipan® PMC green vs. placebo after 30 days
(in vivo shampoo study)

ABSOLUTE DANDRUFF SCORE DANDRUFF REDUCTION

AFTER 30 DAYS
severe 5 0,0

-0,2
4
-0,4

3 -0,6
-0.40
-0,8
2
-1,0
-0.81 -0.76
no dandruff 1
Day 0 Day 30
-1,2
* *
Placebo 0.5% Climbazole 0.5% Crinipan® PMC green

* statistically significant reduction p<0.05 (compared to placebo) 5

Fig. 3 Rinse off shampoo study: Propanediol caprylate reduces dandruff significantly in a 30 days study vs placebo and achieves comparable
results to the established anti-dandruff benchmark climbazole.

Results druff associated species, particularly low values between 500

and 1000 ppm were found (Fig. 2).
In vitro Efficacy The antimicrobial activity of propanediol caprylate is direct-
ly activated by the Malassezia fungus. Natural Malassezia
Caprylic acid is known for its antifungal activity but its strong lipases cleave the ester and release the actual active (ca-
odor limits topical application for cosmetics. Therefore, the prylic acid). This activity has been confirmed in vitro. A sig­
respective ester, propanediol caprylate, was developed as nifi­cant decrease in concentration of propanediol caprylate
anti-­dandruff active. Similar antimicrobial activity is also de- was measured within hours of inoculation with the fungus
tected for the odorless ester. with simultaneous increase of the concentration of caprylic
For this purpose, representative Malassezia strains were test- acid (Fig. 1). The rate of conversion from propanediol ca-
ed and minimum inhibitory concentrations (MIC) determined, prylate to caprylic acid can be increased by adding higher
which ranged from 500 to 2000 ppm. Especially for the dan- numbers of cells.

In vivo Efficacy
bb. 4
A statistically significant reduction on the absolute dandruff
score versus placebo was found for the two actives pro-
panediol caprylate and climbazole (positive control) in an
in vivo rinse-off shampoo study with 82 subjects split into
three groups respectively. Notably the addition of the new
molecule, propanediol caprylate, to a shampoo leads to
parity in effectiveness to the established active climbazole
(Fig. 3).

Physicochemistry:
Effect on Foam and Sensorial Properties

The addition of propanediol caprylate to shampoo formula-

tions leads to a significantly smaller bubble size, but higher
bubble count vs. placebo. This effect indicates an increased
foam stability and leads to improved cleaning properties and
better skin feel. The results were confirmed in vivo on wet
skin: 91% of panelists reported a higher foam volume during
shampoo application containing propanediol caprylate. Fur-
Fig. 4 Physicochemical behavior: Propanediol caprylate improves
thermore a softer skin feel was confirmed by 75% of the pan-
foam and sensorial experience on skin.
elists vs. placebo (Fig. 4).

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personal care | scalp care

Conclusion References
[1] Symrise CICS database 2016, 2018 20-22 countries; Scalp Care Exploration
Study 2020, 5 countries.
Propanediol caprylate represents a novel and effective an-
[2] Symrise patent 2015, EP3364938B1, Mixtures Comprising Climbazole.
ti-dandruff technology that is able to compete with conven-
[3] Symrise AG; May 2020, Crinipan® AD – Reliable and Well-Established anti-dan-
tional actives. The efficacy is based on caprylic acid’s activity, druff active; https://www.symselect.com/dandruff-control
but can be achieved by use of the ester technology. Use of this [4] X. Lin, A. Nomachi, J. Yang, Cosmetics & Toiletries 2019, June, Vol. 134, No. 6,
p 65-70, Rise to the Top - Decylene Glycol for Scalp Health and Care.
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[5] Symrise Patent 2007, EP2063853B1, Use of C10-C14-Alkanediols in the Prepa-
physicochemical benefits on foam quality and skin feel but ration of a Composition for the Prophylaxis and / or Treatment of Malassezia-­
Induced Dandruff Formation and Compositions Comprising C10-C14-Alkane-
bypasses disadvantages of the acid, such as a bad odor pro- diols.
file. Propanediol caprylate is made by green chemistry from [6] US Food&Drug Administration (FDA); May 2020; https://www.fda.gov/drugs/
100% plant based feedstock. This satisfies the increasing de- status-otc-rulemakings/rulemaking-history-otc-dandruff-seborrheic-dermatitis-
and-psoriasis-drug-products
mand for sustainability and naturalness in personal care.
[7] E. Rannou, Guidebook for Exporting/Importing Cosmetics to Japan, EU-Japan
Centre for Industrial Cooperation, Tokyo, January 2015; https://www.eu-japan.
eu/sites/default/files/publications/docs/cosmetics-japan.pdf, May 2020.
Acknowledgements
[8] Symrise patent submission 2016, EP3500236A1, A Preservative Mixture.
We thank Prof. Dr. Peter Mayser, a renowned dermatologist
[9] P. Mayser, Mycoses 2015, 58(4): 215-219., Medium chain fatty acid ethyl es-
and dedicated expert in Malassezia research for his constant ters – activation of antimicrobial effects by Malassezia enzymes.
support during our joint research project with the University [10] C. Koch, M. Pesaro, G. Schmaus, P. Mayser; Mycoses 2020, 63(7):704-710,
of Giessen. On the Symrise side, Jessica Grieger and Ricarda Medium chain fatty acid esters – optimizing their efficacy as anti-Malassezia
agents.
Kraeling supported this project extensively with microbio­logi­ [11] Symrise patent submission PCT_EP2019_
cal and physicochemical analyses. Dr. Steffen Nordzieke ac- 052576; Fatty acid esters as anti-­
contact
Malassezia agents.
companied the project especially during the late development
[12] Symrise patent submission PCT_EP2020_
phase. Thanks also to Dr. Sabrina Behnke for her professional 051507; Antimicrobial activity of fatty
input in correcting this manuscript. acid esters and combinations thereof. Dr. Florian Genrich
[13] Symrise patent submission PCT_EP2019_ [email protected]
052582; Active agents for skin and hair
care with physicochemical modifying Symrise AG
properties.
Cosmetic Ingredients Division
[14] Symrise patent submission PCT_EP2019_
052578; Active agents for skin and hair
BU Micro Protection
care with sensory modifying properties. Holzminden | Germany
[15] P. T. Anastas, J. C. Warner, Green Chem-
istry: Theory and Practice, Oxford Uni- Dr. Christin Koch, Sabine Lange,
versity Press: New York, 1998, p. 30.
Dr. Nikolas Bugdahn, Dr. Gerhard Schmaus
[16] J. Otera, Chem. Rev. 1993, 93 (4),
1449-1470, Transesterification. Symrise AG
[17] J. Otera, J. Nishikido; Esterification: Global Innovation Cosmetic Ingredients
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Wiley-­VCH, 2003, p. 5, 10. Holzminden | Germany

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