Take a closer look

at protection
RonaCare® CPC and
RonaCare® Cetrimonium Bromide
Fine-tune Your Formulations
Merck’s effective, dual-functional antimicrobial protection
Artists pay close attention when they mix their paints since it may not take much pigment to create
the right color. The same applies to antimicrobial substances – they too are effective at low levels.
Thus even a small amount is highly beneficial for the protection against mircoorganisms – a must
in our modern life since they can affect the consumer negatively in several ways.

The appropriate use of preservatives or antimi-

The importance of protective measures becomes
evident when one bears in mind that even the
air around us contains innumerable microbes,
both harmless and pathogenic, all of which at-
tempt to settle on a suitable nutrient – namely
the skin or an opened cosmetic product – in
order to develop or reproduce.
Depending on the site of action, an ingredient
is called an “antimicrobial” if you focus on skin
protection and a “preservative” when you want
to protect a product. In both cases, the objective
is to inhibit the growth of microorganisms.
crobials highly influences the development of
new and innovative products. The preservatives
and antimicrobials must support a long life
cycle for the product plus give maximum pro-
tection to the skin, enabling a minimal forma-
tion of odor, for example sweat or bad mouth/
breath odor. Merck offers two outstanding prod-
ucts to com­­bat mircoorganisms: RonaCare® CPC
and RonaCare® Cetrimonium Bromide. They
represent quaternary ammonium salts (quats,
amphoteric surface active substances) with ap-
proved antimicrobial and fungicidal effects and
additional spectrum of action, for example anti-
static properties.
Literature
1. C.R. Birnie, et al., “Antimicrobial evaluation of N-alkyl
betains and N-alkyl-N, N-dimethylamine oxides with
variations in chain length,” Antimicrob. Agents
Chemother. 44 (2000): 2514–2517.
2. S.B. Lee, et al., “Permanent, nonleaching antibacterial
surfaces. 1. Synthesis by atom transfer radical polym-
erization. Biomacromolecules 5 (2004): 877–882.
 Regulatory Affairs
The use of RonaCare® CPC and RonaCare® Cetrimonium Bromide preservatives is illustrated in the
table below. The utilization of active ingredients in the EU is under the responsibility of the Cosmet-
ics Regulation (EC) 1223/2009 which gives a clear definition regarding preservatives. The use of skin
antimicrobials as active ingredients is under the responsibility of the manufacturer in many countries
such as the EU. However, the USA and Japan have established further stringent regulations which
must be taken into account. The final decision in using active ingredients in cosmetic products listed
in the table below is the responsibility of our customers, considering all relevant regulations.

Preservative Antimicrobial Use Other

EU USA JAPAN EU USA JAPAN
EU/USA/JAPAN
Positive List: Not specifically “Standards for Not specifically OTC drug Quasi-drug
Annex V regulated Cosmetics regulated
Regulation (EC) (Notification
1223/2009 No. 331 of
2000)”
If CPC is used in a cosmetic
OTC drug, product or in a product other
RonaCare® Category I, than drug use, e.g. as an emulsi-
CPC l l l(1) l Oral care l(3) fier, a wetting agent or as an
ingredients(2) anti-static agent, it is classified
as a cosmetic ingredient.
If cetrimonium bromide is used
in a cosmetic product or in a
RonaCare® product other than drug use,
Cetrimonium l l l l l l(3) e.g. as an emulsifier, a wetting
agent or as an anti-static agent,
Bromide
it is classified as a cosmetic
ingredient.

l Use permitted l Use not permitted

(1) Restrictions in three categories: permitted as preservative according to the “Standards for Cosmetics (Ministry of
Health and Welfare Notification No. 331 of 2000)”
Category 1 - Cosmetics which are not applied on mucous membranes and are washed away immediately after
application: maximum concentration 5.0 g /100 g
Category 2 - Cosmetics which are not applied on mucous membranes and are not washed away immediately
after application: maximum concentration1.0 g /100 g
Category 3 - Cosmetics which are applied on mucous membranes: maximum concentration 0.01 g /100 g
(2) Proposed rule
(3) Japan Pharmaceutical Affair Law Notification 990 (September 29, 2000)

Literature
“Preservative regulations: a global overview,” Personal
Care Magazine, January 2009: 67–73.
 RonaCare® CPC
Make it part of your complete oral care package
The active ingredient in RonaCare® CPC is
cetylpyridinium chloride, a cationic wetting and/
or surface-active agent, similar to soap, that has
bactericidal properties. RonaCare® CPC is very
effective in the following applications.
Oral care products
RonaCare® CPC is effective in preventing dental
plaque, protecting against tooth decay and
reducing gingivitis. Owing to its surface activity
or wetting properties, it is especially effective in
reaching wrinkles and pockets of mucous in the
mouth. The bacteria-filled phlegm of the mucous
membrane is removed, even in areas that are
difficult to access. It is effective in mouthwashes
and sprays. With products such as fluorine
sources RonaCare® NaF and RonaCare® Olaflur
or with RonaCare® Calcium Carbonate, made
epecially suitable for dental care, RonaCare®
CPC can offer beneficial aspects for after-
treatment applications. It supplements the
oral care package.
Ordering Information
Item No. Name Package Size
102340 RonaCare® CPC 2.5 kg, 25 kg, 100 g sample
Hair care products
RonaCare® CPC can be used in shampoos for the
symptomatic treatment of dandruff. Moreover,
hair becomes soft and silky when treated with it
– an ideal component for hair styling products.
The agent imparts sheen and anti-static proper-
ties to hair, making it appropriate for hairsprays,
setting lotions, hair colorants and as a supple-
ment to cold-wave preparations.
Skin care products
Its wide spectrum of performance such as sub-
stantivity on skin and hair, foaming, emulsifying
and antimicrobial properties make RonaCare®
CPC suitable for other products, for example
deodorants and antiperspirants. It also can be
used in shaving lotions or wet wipes.
Technical Data
INCI Name Cetylpyridinium Chloride
Appearance White powder
Solubility Water: 8 g/100 ml (20 °C)
Ethanol: 30 g/100 ml
Stability Stable under standard conditions
Applications
• Oral care: use level 0.05–0.1%
• Hair care: use level 0.1–1.0%
• Skin care: use level 0.05–0.5%
For Your Information
• pH optimum for efficacy: 4–10
• The bactericidal effect is reduced by the pres-
ence of anionic-active substances, salicyclic
acid, talc, kaolin and polyphosphates owing
to the formation of insoluble precipitates.
• Incompatible with a number of high-molecu-
lar compounds commonly used as thickening
agents including carboxymethyl cellulose,
alginates, gelatin and tragacanth.
Spectrum of Activity
RonaCare® CPC protects against gram-positive
and gram-negative bacteria as well as fungicidal
attacks. It therefore offers a broad spectrum to
protect skin and products.
Classification of bacteria
The classification of bacteria is based on a bac-
terial staining method developed by the Danish
doctor Gram in 1884. This staining method
allows a clear color-based classification. Gram-
positive bacteria retain a violet color. Families
of gram-positive bacteria are: micrococci, strep-
tococci, staphylococci, corynebacteria, lactobac-
teria and bacilli. Gram-negative bacteria, on the
other hand, retain a red color. Families of gram-
negative bacteria are: Neisseria family, nitrobac-
teria, azotobacteria, rhizobiacea, psoedomonas
family and enterobacteria.
Literature
1. A. Bosy, “A review of oral products for the treatment of
mouth odor,” ADHA InTouch, (2004): 4–6.
2. O. G. Clausen, “An examination of the bacteriostatic and
bactericidal, fungistatic and fungicidal effects of cetyl-
pyridinium chloride and 2-bromo-2-nitropropan-1,3-di-
ol, separately and in combinations also including benzyl
alcohol,” Pharm. Ind. Vol. 35 No. 11 (1973): 726–729.
3. O. G. Clausen, “An examination of the bactericidal and
fungistatic effects of cetylpyridinium chloride, sepa-
rately and in combinations embodying EDTA and benzyl
alcohol,” Pharm. Ind. Vol. 35 No. 12 (1973): 869–874.
4. Jan-Frederik Güth, Klinische Studie zur “Untersu­
chung der Effektivität zweier Mundspüllösungen mit
antibakteriellen Wirkstoffen bei der Bekämpfung und
Entstehung von Mundgeruch,” 2008.
5. S. Jenkins, et al., “A comparison of cetylpyridinium chlo-
ride, triclosan and chlohexidine mouthrinse formula-
tions for effects on plaque regrowth,” Journal of Clinical
Periodontology Vol. 21 (1994): 441-444.
6. N. N., “Quaternäre Ammoniumverbindungen in der
Kosmetik,” Österreichische Apotheker-Zeitung Vol. 17
(1963): 386.
Fungicidal Activity of RonaCare® CPC
Killing times for a concentration of 1:100 at 22 °C
Trichophyton mentagrophytes < 24 hours
Candida albicans < 24 hours
Aspergillus fumigatus < 24 hours
Microsporum audouini < 24 hours
Histoplasma capsulatum < 24 hours
Bactericidal* Activity of RonaCare® CPC
Killing times for concentrations ranging from
1 : 10,000 to 1 : 100,000 at 22 °C
Gram-positive bacteria
Staphylococcus aureus 2 min.
Streptococcus pyogenes
Gram-negative bacteria
Escherichia coli
2 min.
Pseudomonas aeruginosa
Proteus vulgaris
7. Y. Pomeranz, “Inactivation of a-amylase by synthetic
detergents,” Biochem. Biophys. Acta Vol. 73 (1963): 105;
ref. Chem. Abstr. 59, 14382e (1963).
8. E. L. Prince, et al., “The efficacy of cetylpyridinium chlo-
ride glove coatings against staphylococcus epidermidis
and staphylococcus aureus,” International Biodeteriora-
tion & Biodegradation Vol. 39, No. I (1997): l-7.
9. P. Renton-Harper, et al., “A comparison of chlorhexi-
dine, cetylpyridinium chloride, triclosan, and C31G
mouthrinse products for plaque inhibition,” Journal of
Periodontology Vol. 67, No. 1 (1996): 486–489.
10. A. R. Volpe, et al., “Antimicrobial control of bacterial
plaque and calculus and the effects of these agents on
oral flora,” Journal of Dental Research Vol. 48 (1969):
832.
11. G. Welter, et al., “Cetylpyridinium reduziert Zahn-
plaques,” Deutsche Apotheker Zeitung Vol. 123, No. 9
(1983): 421–422.
12. B. Zdralek, “Quarternäre Ammoniumverbindungen in
der Kosmetik,” Seifen-Öle-Fette-Wachse Vol. 84 (1958):
697.
 RonaCare® Cetrimonium Bromide
Formulate safe, effective, long-lasting hygiene products

Technical Data
INCI Name Cetrimonium Bromide
Appearance White powder
Solubility Water: 0.3 g/100 ml (20 °C)
0.2 g/100 ml (25 °C)
Ethanol: 18 g/100 ml
Stability Stable under standard conditions

Applications
• Hair care: use level 0.1–1.0%
• Skin care: use level 0.5–1.0%

The active ingredient in RonaCare® Cetrimonium

Bromide is cetyltrimethylammonium bromide For Your Information
and has proven to be very effective in the fol-
lowing applications. • pH optimum for efficacy: 4–10
• Being a cationic surfactant, cetrimonium bro-
Hair care products mide is liable to foam in aqueous solutions
Owing to its fungicidal and bactericidal actions, and is incompatible with anionic surface-
RonaCare® Cetrimonium Bromide is used as an active agents as well as peptides, polymer
anti-dandruff additive in shampoos and hair lo- phosphates and zinc salts.
tions. Since it makes hair glossy and more man- • Cetrimonium bromide is also incompatible
ageable, it is also incorporated into conditioners, with alkalis, proteins and a number of high-
setting lotions, hair rinses, hair styling products molecular compounds commonly used as
and hair colorants. thickening agents such as agar-agar, car-
boxymethylcellulose, alginates, gelatin and
Skin care products tragacanth.
RonaCare® Cetrimonium Bromide is formulated
into a wide range of skin care products including
deodorant, where it assists in preventing unpleas-
ant body odor which results from microbial de-
composition of perspiration, to bath and shower
products. Its ability to control and kill bacteria
and protect skin makes it appropriate for shav-
ing creams, aftershaves, acne treatments, face
cleansers, face creams, exfoliating gels, hygiene
products such as wet wipes and much more.

Ordering Information
Item No. Name Package Size
102343 RonaCare® Cetrimonium Bromide 1 kg, 25 kg 100 g sample
Spectrum of Activity
RonaCare® Cetrimonium Bromide has shown
good bacteriostatic and bactericidal action
against a number of gram-positive and gram-
negative germs in various tests. Good fungicidal
effects also have been achieved for some test
strains where its fungicidal activity was found to
be superior to that of other quaternary ammo-
nium salts.

Fungicidal Activity of RonaCare® Cetrimonium Bromide

Killing times for various concentrations; Temperature 22 °C
Concentration 1 : 100 1 : 200 1 : 1,000 1 : 2,000 1 : 10,000
Trichophyton mentagrophytes 10 min. 4 hours 4 hours 4 hours 24 hours
Candida albicans 24 hours
Aspergillus fumigatus 24 hours
Microsporum audouini 10 min. 10 min. 30 min. 30 min. 1 hour
Histoplasma capsulatum 10 min. 24 hours

Bacterial Activity of RonaCare® Cetrimonium Bromide

Killing times for various concentrations; Temperature 22 °C
Concentration 1 : 10,000 1 : 20,000 1 : 40,000 1 : 100,000
Escherichia coli 2 min. 2 min. 2 min. 30 min.
Pseudomonas aeruginosa 2 min. 2 min. 2 min. 5 min.
Staphylococcus aureus 5 min. 5 min. 5 min. 5 min.
Streptococcus pyogenes 2 min. 2 min. 2 min. 2 min.
Proteus vulgaris 2 min. 2 min. 2 min. 5 min.

Literature
1. P. Benigno and T. Berti, “Antibacterial action of cetyl-
trimethylammoniumbromide of escherichia coli: effect
of short contact,” Arch. intern. pharmacodyn. Vol 93
(1953): 412; ref. Chem Abstr. 48, 9459b (1954).
2. Ch. M. Cousins, “Bacteriological screening test for
quarternary ammonium compounds and formulations,”
Proc. Soc. Appl. Bacteriol. Vol. 14 (1951): 184; ref.
Chem. Abstr. 49, 5779d (1955).
3. R. Frank and G. Stark, “Über die antibakterielle
Wirkung von Acriflavin und Cetyltrimethylammonium-
bromid in versch. Salbengrundlagen,” Pharm. Acta Helv.
Vol. 29 (1954): 81.
4. J. C. Hoogerheide, “The germicidal properties of certain
quarternary ammonium salts with special reference
to cetyltrimethylammoniumbromide,” J. Bact. Vol. 49
(1945): 277; ref. Chem. Abstr. 39, 28467 (1945).
5. J. S. Jellinek, Kosmetologie (Heidelberg: Dr. Alfred
Hüthig Verlag, 1959): 78, 267.
6. A. Kluge, “Die Eigenschaften quartärer Ammonium-
salze und ihre Verwendung in kosmetischen Mitteln
zur Behandlung der Haare,” Parfümerie und Kosmetik
42 (1961): 341.
7. E. S. Lambert, “Kationaktive Verbindungen als Zusätze
zu Kosmetika,” Kosmetik-Parfüm-Drogen-Rundschau
Vol. 10 (1963): 141.
8. N. N., “Quarternäre Ammoniumverbindungen in der
Kosmetik,” Österr. Apotheker-Zeitung 17 (1963): 24,
386.
9. G. Nicoletti, et al., “The antimicrobial activity in
vitro of chlorhexidine, a mixture of isothiazolinones
(‘Kathon’ CG) and cetyl trimethyl ammonium bromide
(CTAB),” Journal of Hospital Infection Vol. 23 No. 2
(1993): 87–111.
10. A. Obayashi, “Action of surface active agents on mi-
croorganisms. The germicidal action and the effect on
permeability,” Nippon Nogeikagaku Kaishi 35 (1961):
61; ref. Chem. Abstr. 60, 11093e (1964).
11. W. Paulus, Ed., Directory of microbicides for the protec-
tion of materials (Springer, 2005): 708.
12. H. H. Rodin, “Treatment of primary and secondary
infections of the skin with cetyltrimethylammonium-
bromide,” J. pharm. Sci. 51 (1962): 1107.
MERCK provides information on application technologies and relevant regulations based upon our current knowledge
and opinion at the time of printing. MERCK makes no representation or warranty of any kind, express or implied,
including merchantability or fitness for a particular use, with respect to such information or its application. Purchasers
must independently determine the suitability of our ingredients for the purchaser’s intended product, use or process.
Purchaser is responsible for observing all laws and regulations relevant to such products, uses or processes. The fore­
going information and suggestions are also provided without warranty of non-infringement as to the intellectual prop-
erty rights of third parties, and shall not be construed as any inducement to infringe the rights of third parties.

Release date: December 2011

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