FIELD OF THE INVENTION
The present invention relates to hair care formulations having reduced amount of anti-
dandruff actives used without affecting the expected effects. More particularly the present
invention relates to formulations comprising the synergistic combination of azole based anti-
dandruff actives comprising 2-mercaptobenzimidazole with another anti-fungal and anti-
bacterial agent. The anti-dandruff active, 2-mercaptobenzimidazole derivatives possessing
significant anti- malassezia activity-displays significant synergistic effects when combined
with zinc pyrithione thus helps in combating the toxicological effect of ZPTO
BACKGROUND AND PRIOR ART OF THE INVENTION
Zinc pyrithione is approved for topical use as a treatment for dandruff. However, in its
industrial forms and strengths, it may be harmful by contact or ingestion. Recent research
suggests that zinc pyrithione is a potent heat shock response inducer that may cause DNA
damage and PARP-dependent energy crisis in cultured human keratinocytes and
melanocytes.
Zinc pyrithione and ketoconazole are known in prior art to be highly effective against
dandruff causing pathogens. One of the key causative factors for dandruff is Malassezia spp.
Dandruff treatments mainly focus on actives that are anti Malassezia and are incorporated in
various types of formulations. In spite of their effectiveness, they are also associated with
side effects such as skin irritation and toxicity. As a result they are restricted to a maximum
of 2% (by weight) in hair care formulations.
In prior art there are many documents which relate to the anti dandruff formulation
comprising combination of ZPTO with other anti- microbial agents. But none of them
discloses the combinational effect of ZPTO with other anti-fungal agents like benzimidazole
derivatives.
US 3236733 describe a method of combating dandruff using pyridinethione metal salts (e.g.
zinc pyridinethione) detergent compositions.
DE 2262375 also shows the use of soluble combinations of zinc and zirconium pyrithiones to
provide effective antidandruff treatment.
While the metal salts and other derivatives of l-hydroxy-2-pyridinethione and its tautomeric
form 2-pyridinethiol-1-oxide (or 2-mercaptopyridine-N-oxide) are known to be effective
bacteriocides and fungicides for use in medicated shampoos for the treatment and control of
dandruff, the toxicity of these compounds is relatively high and, in many instances, they are
extremely irritating to the skin and eyes. The reported 24-hour acute oral lethal dose (LD50)
of zinc pyrithione is 300 mg/kg in mice and 200 mg/kg in male rats. The 24 hour acute LD50
of sodium pyrithione is approximately 1100 mg/kg in rats. A 40% solution of the sodium
pyrithione does not irritate rabbit eyes but does irritate the skin. A 48% dispersion of the zinc
pyrithione irritates the skin and is extremely irritating to the eyes of rabbits.
US 2009/0226384 discloses the synergistic antimicrobial composition and a process for its
preparation containing an antimicrobial agent such as Triclosan (TCS) and the functionalized
hydrocarbon and/or mixtures containing such fiinctionalized hydrocarbons in the ratio in the
range of 1:5 - 1:100. But synergy between antifungal agents has not been disclosed in this
patent.
US 4307089 disclose antimicrobial compositions useful in the preparation of cosmetic
formulations, including preparations effective for the treatment of dandruff. The
antimicrobial compositions consist of a pyrithione compound in combination with an
undecylenic acid monoalkylolamide sulfosuccinate half ester exhibiting better scale-
suppressing effect than the shampoo formulation prepared using a higher concentration of the
zinc pyrithione. It provides the effective dandruff control with shampoo formulations
containing 0.4 wt. percent zinc pyrithione.
Thus there is a need to develop both new actives and new technologies that help reduce the
amount of anti dandruff actives like ZPTO to a non-toxic level without affecting the expected
benefits.
OBJECTS OF THE INVENTION
It is an object of the invention to overcome the drawback of the prior art.
It is another object of the invention to provide hair care formulation comprising reduced
amount of anti dandruff actives to a non-toxic level.
It is another object of the invention to provide a synergistic combination of 2-
mercaptobenzimidazole derivatives and Zinc pyrithione.
SUMMARY OF THE INVENTION
According to one aspect of the present invention there is provided a hair care formulation
comprising 0.025% to 2% by weight of ZPTO and 0.025% to 2% by weight of 2-
mercaptobenzimidazole derivative.
BRIEF DESCRIPTION OF THE ACCOMPANYING FIGURES
Figure 1 represents the structural formula of the molecules and their tautomers.
DETAILED DESCRIPTION OF THE ACCOMPANYING FIGURE
Figure 1 displays the structural formula of the molecules and the tautomers wherein R1 = H,
alkyl, aryl, heteroaryl, hydroxy, alkoxy, substituted alkoxy, NO2, halogen, amine, R2 = H,
alkyl, aryl, heteroaryl. The 2-mercaptobenzimidazole derivative preferred for the present
invention is 5-nitro-2-mercapto benzimidazole
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to antidandruff formulation for treating the hair and the scalp,
based on an antidandruff agent. The present invention aims to provide a system/technology
for reducing the amount of anti-dandruff actives used in formulations without affecting the
expected effects. In spite of the reduction in amount, the resulting formulations exhibit
enhanced activity compared to the known formulations having a higher amount of ZPTO.
In view of the reduced amount of the pyrithione compound which can be employed, a
significant economic advantage can be realized and the compositions and the resulting
formulations prepared therefrom are toxicologically more desirable. Furthermore, synergistic
combinations result so that it is possible to obtain products which exhibit enhanced
antimicrobial activity. While it is highly desirable, based on economic considerations alone,
to replace the pyrithione component with less costly material, there is also requirement by
regulatory bodies, based on toxicological considerations, to limit the effective amount of
pyrithione derivatives in cosmetic formulations. As a result of this invention it is now
possible to prepare effective cosmetic formulations which satisfy, for example, the
requirements of the Europarat, a public body which in study published in 1978 recommended
that the concentration of sodium pyrithione, for instance, be limited to a level of 0.5%.
Reduction of the concentration of zinc pyrithione to a maximum level of 1%, calculated as
zinc, has also been recommended by the "Kosmetikverordnung" as published on Dec. 16,
1977 on behalf of the "Deutsche Bundesgesundheitsamt".
More particularly, the present invention provides an anti-dandruff formulation having
enhanced activities of 2-mercaptobenzimidazole derivatives and Zinc pyrithione. The anti-
dandruff active, 2-mercaptobenzimidazole derivatives possessing significant anti Malassezia
activity displays significant synergistic effects when combined with zinc pyrithione.
2-mercaptobenzimidazole derivatives, the azole based anti-dandruff actives possess
significant anti Malassezia activity. These molecules and their tautomers have the structural
formula shown in Figure 1 wherein R1 = H, alkyl, aryl, heteroaryl, hydroxy, alkoxy,
substituted alkoxy, NO2, halogen, amine, R2 = H, alkyl, aryl, heteroaryl. The 2-
mercaptobenzimidazole derivative preferred for the present invention is 5-nitro-2-mercapto
benzimidazole
During the present study it has been observed that the combined actives, even when used at
much lower concentrations, display far superior activity when compared to the individual
activities due to synergy.
In the present invention a synergistic effect between the 2-mercaptobenzimidazole derivative
and ZPTO has been observed. Such synergistic effects were not observed when climbazole
and 5-nitro-2-mercapto benzimidazole were combined. Climbazole is also a topical
antifungal chemical commonly used in the treatment of human fungal skin infections like
dandruff and eczema. Its chemical structure and properties are similar to other fungicides like
ketoconazole and miconazole.
By combining 5-nitro-2-mercapto benzimidazole, it is possible to effectively reduce the
amount of pyrithione derivative to the levels recommended by the aforementioned agencies
and thereby improve the overall toxicological properties of the resulting cosmetic
formulations without detracting from their desirable characteristics.
The present invention thus helps in significantly reducing the amount of ZPTO to upto 0.25%
providing enhanced activity. The hair care formulation of the present invention includes
shampoos, conditioners, serums and creams.
The actives of the present invention are 5-nitro-2-mercapto-1H-benzimidazole and ZPTO.
The preferred amount of the same is 0.05 to 1.75% and 0.05 to 1% respectively.
As mentioned above the actives are formulated into various hair care formulations.
The surfactant in the present formulation is selected from anionic, cationic, nonionic,
amphoteric and zwitter ionic surfactants.
The term 'surfactant' means an ingredient that is used in a cosmetic formulation and exhibits
the ability to reduce the interfacial tension between two immiscible substances, wets skin and
hair surfaces, emulsifies or solubilizes oil. The term is synonymous with wetting agents,
surface cleansing agents, surface-active agents and the like.
Suitable anionic surfactants of the present invention include, but are not limited to, the alkyl
sulphates, alkyl ether sulphates, alkaryl sulphonates, alkanoyl isethionates, ^Ikyl succinates,
alkyl sulphosuccinates, N-alkoyl sarcosinates, alkyl phosphates, alkyl ether phosphates, alkyl
ether carboxylates, and alpha-olefin sulphonates, especially their sodium, magnesium,
ammonium and mono-, di- and triethanolamine salts. The alkyl and acyl groups generally
contain from 8 to 18 carbon atoms and may be unsaturated. The alkyl ether sulphates, alkyl
ether phosphates and alkyl ether carboxylates may contain from 1 to 10 ethylene oxide or
propylene oxide units per molecule, and preferably contain 2 to 3 ethyene oxide units per
molecule. Examples of suitable anionic surfactants of the present invention include, but are
not limited to, sodium oleyl succinate, ammonium lauryl sulphosuccinate, ammonium lauryl
sulphate, sodium dodecylbenzene sulphonate, triethanolamine dodecylbenzene sulphonate,
sodium cocoyl isethionate, sodium lauroyl isethionate and sodium N-lauryl sarcosinate. The
most preferred anionic surfactants are sodium lauryl sulphate, triethanolamine lauryl
sulphate, triethanolamine monolauryl phosphate, sodium lauryl ether sulphate 1EO, 2EO, and
3EO, ammonium lauryl sulphate and ammonium lauryl ether sulphate 1EO, 2EO and 3EO.
Suitable cationic surfactants of the present invention include, but are not limited to,
quaternary ammonium and esterquats, more particularly quatemized fatty acid
trialkanolamine ester salts, aliphatic mono, di and polyamines derived from fatty and rosin
acids, amine oxides, ethoxylated alkyl amines and imidazolines.
The nonionic surfactants of the present invention suitable for use in formulations of the
invention may include condensation products of aliphatic (C8-C18) primary or secondary
linear or branched chain alcohols or phenols with alkylene oxides, usually ethylene oxide and
generally having from 6 to 30 ethylene oxide groups. Other suitable nonionics include mono-
or di-alkyl alkanolamides. Example includes coco mono- or di- ethanolamide and coco
mono-isopropanolamide.
The amphoteric and zwitterionic surfactants suitable for use in formulations of the invention
may include alkyl amine oxides, alkyl betaines, alkyl amidopropyl betaines, alkyl
sulphobetaines (sultaines), alkyl glycinates, alkyl glycinates, alkyl carboxyglycinates, alkyl
amphopropionates, alkylamphoglycinates alkyl amidopropyl hydroxysultaines, acyl taurates
and acyl glutamates, wherein the alkyl and acyl groups have from 8 to 19 carbon atoms.
Examples include lauryl amine oxide, cocodimethyl sulphopropyl betaine and preferably
lauryl betaine, cocamidopropyl betaine and sodium cocamphopropionate.
Generally, the surfactants are present in formulations of the invention in an amount of from
15 to 50%, preferably from 10 to 30%, more preferably from 5 to 25% by weight.
The other ingredients in the present formulation are selected from conditioning systems,
moisturizing systems, additives, and anti-inflammatory agents.
As used herein the term 'conditioning system' refers to individual or combination of hair care
products that help in improving at least one of the sensorial of touch, feel, softness, volume,
manageability and appearance of hair or fibres. The term is synonymous with a hair care
product capable of providing a soft feel to the coat and provides hairs that lay flat and are
easily combable.
The conditioning system for use in the present invention further comprises suitable
dimethiconol microemulsion which is commercially available in a pre-emulsified form. Such
pre-formed emulsions can be incorporated into the formulation by simple mixing, which is
particularly advantageous for ease of processing. Pre-formed emulsions are available from
suppliers of silicone oils such as Dow Coming, General electric. Union Carbide, Wacker
Chemie, Shin Etsu, Toshiba, Toyo Beauty Co, and Toray Silicone Co.
The conditioning system for use in the present invention may also contain high molecular
weight cationic polymers. Preferred cationic polymers used in the formulation are
acrylamidopropyltrimonium chloride/acrylamide copolymer and polymeric quaternary
ammonium salt of hydroxyethyl-cellulose.
Cationic surfactants such as mono-, di- and tri-alkyl quaternary ammonium salts may also be
used as the cationic conditioning agent. Suitable examples are cetyl trimethylammonium
chloride, cetyl trimethylammonium bromide and stearyltrimethylammonium chloride.
The term 'moisturizing system' as used herein refers to chemical compositions and
combinations thereof which when applied provide a moisturizing effect to hair follicles.
The term 'moisturizing effect' as used herein refers to effects shown by moisturizers such as
retention/increase in water content, holding and redistribution of water and maintenance of
the integrity and appearance of hair.
'Moisturizer' refers to the action of a material, which after one or more applications,
minimized to a desired extent whatever drying effect a shampoo might have on the hair of an
animal. The preferred moisturizing system for use in the present invention comprises of zinc
salt of L-pyrrolidone carboxylic acid (L-PCA) acid and hydroxyethyl urea.
Anti-inflammatory agents which may optionally be added to the formulations of the present
invention may be chosen from allantoin, phytic acid, lutein, azulene, forskolin, adandrine etc.
The formulation of the present invention may further comprise one or more of the
conventional optional components known for use in hair care formulations, provided that the
components used are compatible with the essential components of the formulation both
physically and chemically. These optional components should generally not impair the
stability, aesthetics or performance of the product. Concentrations of such optional
components typically range from about 0.001% to about 10% by weight of the formulation.
Such conventional optional ingredients are well known to those skilled in the art and may be
selected from the group comprising but not restricted to preservatives such as benzyl alcohol,
methyl paraben, propyl praben, imidazolidinyl urea, methylchloroisothiazolinone; thickeners
and viscosity modifiers such as coconut ethanolamide, sodium chloride, ammonium chloride,
sodium sulfate, carboxymethyl cellulose, methyl cellulose, polyvinyl alcohol, and ethyl
alcohol; perfumes; dyes; sequestring agents such as disodium ethylenediamine tetraacetate;
pH adjusting agents such as citric acid, phosphoric acid, sodium hydroxide, sodium
carbonate, etc.
The present invention is now demonstrated by way of illustrative non - limiting examples.
Other variations as may be obvious to one skilled in the art may be made in compounds,
formulations, and methods described herein without departing from the essential features of
the invention. These and such others may be considered illustrative and non restrictive to the
scope of the present invention.
Example 1
18 samples were prepared by dissolving the actives in DMSO in amounts as provided in
Table 1. The in vitro anti-malassezia activities of the solutions were then assessed through
zone of inhibition methodas per BIS ISl 1479 (Part 2): 2001, i.e., measuring the clear zone of
inhibition of growth around the disc containing the active ingredient.
The results are depicted in Table 1
Table 1. Synergistic effect between anti-dandruff actives.
aThe actives were dissolved in DMSO. ''By disc diffusion method.
Table 1 illustrates the synergistic effects of the combination of 2-mercaptobenzimidazole and
ZPTO.
It can be concluded from the results as obtained in Table 1 that the same synergistic effects
are not observed when climbazole (another popular antidandruff active) and 5-nitro-2-
mercaptobenzimidazole are combined or even when climbazole is combined with ZPTO.
Accordingly this shows that only the combination of 2-mercaptobenzimidazole derivatives
and ZPTO provides the desired effect.
Example 2
A shampoo formulation according to the present invention comprising the combination of
active 2-mercaptobenzimidazole derivative and ZPTO as mentioned in Table 2 is prepared
and the formulation of the same is provided in Table 2.
Table 2: Comppsition of the present formulation.

Example 3:
Method for the preparation of the shampoo
Phase A: In a 1000 mL thick walled beaker, weighed amount of sodium laureth sulphate,
sodium lauryl sulphate, and Lamesoft P065 (cocoglucoside arid glyceryl oleate) were taken
and heated till 55 °C. To this hot mixture, weighed amount of 5-NMBI (0.25%) was added
and heated to 75 °C.

Phase B: In a separate beaker, polyquatemium 10 was dispersed in weighed amount of water
and acrylamidopropyltrimonium chloride/acrylamide copolymer was slowly added to it. This
dispersed mixture was then added to phase A at 55-60 °C.
Heating was stopped at this point and the above mixture was cooled. Cocamidopropyl betaine
was added at 50°C, followed by addition of polydimethylsiloxane and PEG-15
cocopolyamine below 45°C with continuous stirring. After this, ZPTO suspension (Tomicide
ZP 50) in water was added, stirred for 10 minutes and then acrylate copolymer (Carbopol
Aqua SF-1) was added. The pH of the system was adjusted with NaOH solution. After
neutralizing the system, ginseng extract, yogurtene, allantoin, papain and Zinc PCA were
added, followed by hydroxyethyl urea and preservative (Methylchloroisothiazolinone and
methylisothiazoHnone). Required amount of water was added and the mixture was stirred
further for 10-15 min and then 0.1% sodium chloride solution in water was added. Viscosity
of the system was adjusted to ~4000-5000 cps (preferably by adding more amount of 0.1%
sodium chloride). Finally the pH of the shampoo was adjusted between 6-6.5 (by adding
NaOH).

WE CLAIM:
1. A hair care formulation comprising 0.025 % to 1% by weight of ZPTO and 0.025
to 2% by weight of 2-mercaptobenzimidazole derivative.
2. The hair care formulation as claimed in claim 1, wherein said 2-
mercaptobenzimidazole derivative is 5-nitro-2-mercapto benzimidazole.
3. The hair care formulation as claimed in claim 1, wherein said ZPTO is present
preferably in amount 0.05% to 1% by weight.
4. The hair care formulation as claimed in claim 1, wherein said 2-
mercaptobenzimidazole derivative is present preferably in amount 0.05% to
1.75% by weight.
5. The hair care formulation as claimed in claim 1, wherein said hair care
formulation is selected from shampoos, conditioners, serums and creams.

The present invention relates to a hair care formulation comprising 0.25 % to 2 % by weight
of ZPTO and 0.025% to 2% by weight of 2-mercaptobenzimidazole derivative.