zinc parathion solubility , ,zinc ,parathion ,solutions ,solubility ,hair ,cosmetic dentistry courses, how to solvation the material

1. ]. Soc.Cosmet.
Chem.,25, 99-114(February3, 1972)
ClearZinc Pyrithione
Preparations
TERRY GERSTEIN, M.S.*
Presented
May 24,1971,Seminar,Washington,
D.C.
Synopsis--ZINC PYRITHIONE, also kn,ownas zinc pyridine-2-thiol-l-oxide, has been es-
tablished as an effective ANTISEBORRHEIC AGENT. Because of its limited aqueous
solubilityit is currentlybeingmarketedasa suspension
in hair-cleansing
and hair-grooming
preparations.A methodhasbeendeveloped
in whichclear,aqueous
(aswell asnonaqueous)
productscan be prepared. The method is basedupon the COMPLEXATION of zinc
pyrithione with certain ORGANIC AMINES. It appearsthat zinc pyrithione is highly
solublein manyprimaryaliphaticamines. In othermorecomplexamines,suchasthe poly-
alkylenimines,
a definitestablemolecularcomplexis formed. The ability of suchaminesto
complexand producea solubleform of zinc pyrithioneis discussed
with respectto the
physicaland d•emicalpropertiesof the ensuingsolutions.
Based
onthese
findings,
CLEARHAIR Pi•EPARATIONS
containing
zincpyrithione
can
be preparedfor useasantidandruffcleansers,
rinses,groomingagents,and conditioners. Ex-
amples
areoffered
of productformulations
havinglevels
of zincpyrithione
rangingfrom700
to 20,000
ppm(2%). Analyticaldataconcerning
complex
formationaswell asthe complexes'
toxicologyare presented.
INTRODUCTION
Zinc pyrithione, also known as zinc pyridine-2-thiol-l-oxide
(ZPTO), hasbeenestablished
asan effectiveantiseborrheic
agent(1).
It iscurrentlymarketedin shampoo
and hair dressings
at concentration
levelsof about 0.5% in ,thehair dressing
to about 1•o in the shampoo.
This activeingredientis presentin the form of a dispersed
solid in
these
products
since
itssolubility
isquitelimitedin bothwaterandoil
media. The literature statesthat its solubility in water is 10-20 ppm
at pH 7 andincreases
to 35-50ppmat pH 8 (2). In ethanol,thesolu-
bility is 290ppm; in acetone,
700 ppm; in benzene,
3-5 ppm; and in
diethylether,0 ppm. In other solvents,
the solubilityincreases--for
* RevlonResearch
Center,Inc., 945ZeregaAve.,Bronx,N.Y. 10473.
99

2. 100 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS
example,in chloroform,,to0.34% andin dimethylformamide,
to 0.81%.
The solubilityin dimethylsulfoxide
is reportedto be 5.13% (2). Ac-
cordingly,it hasbeen difficult to formulate suitablecosmetic
composi-
tions containing solubilized ZPTO. Although the sodium salt of
pyrithioneis highly solublein water, and like ZPTO hasbeenfound to
havefungicidaland bactericidalproperties,it, unlike ZPTO, hasbeen
found toxic and unacceptablefor use in cosmetics
or dermatological
compositions
for topicalapplication
to theskin(3).
HYPOTHESES
It waspostulatedthat the solubilityof ZPTO would be increased
in solvents
containingaminofunctionalgroups. The reasoning
for this
isbased
uponthe ability of certainheavymetalssuchascadmium,zinc,
copper,
andnickelto formamminecomplexes.Zinchasa coordination
numberof 4 whichmeansthat it canattachitselfspatiallyto 4 ligand
linkagesbesides
maintainingits two primary valencelinkages. In the
molecularstructureof ZPTO (Fig. 1), two of the four availablespatial
positions
arefilledby the oxygen
in theoxidefunctionalgroups
of the
molecule. A chelateisformed. By selecting
the properaminesolvent
it washopedthat thechelatestructure
wouldbe modifiedto allowfor
the accommodation
of a molecular complex containing amino groups
that would utilize the remaining two Werner bonds.
Figure 1. Zinc pyrithione (zincpyridine-2-thiol-l-oxide)(ZPTO)
One of the first materialsto be testedwasreagentgrade28% am-
moniumhydroxide. It wasfoundthat ZPTO wassolublein it to the
orderof 1 or 270. Althoughthisin itselfwasnot considered
significant,
it provedsomewhat
interesting
whena 1% solutionof ZPTO in am-
moniumhydroxide
wasusedto neutralize
aqueous
Carbopol941.* A
cleargelresultedthat hada pH of 8 andcontained100ppmor 0.01%
ZPTO. When the pH of the gelsystem
waslowered,it wasfoundthat
* B. IV.Goodrich & Co., Cleveland, Ohio.

3. ZINC PYRITHIONE PREPARATIONS 101
the growthof small,finecrystals
had formedthroughout
the media.
Thus,whatin effect
wewereabletodowastoprepare
a near-saturated,
saturated,
or supersaturated
solutionof ZPTO relativelyquicklyand
withoutthepresence
of anequilibrating
solid.
The mechanism
by whichZPTO produces
a therapeutic
effecton
seborrheic
dermatitisis not understood. If one postulates
that the
mechanism
of the actionof ZPTO is throughepidermal
penetration,
thenonemustconcludethat it is not the ZPTO particles
but rather
the molecules
themselves
that penetratethe epidermis. One can then
reason
thattheuseofasaturated
solution
ofZPTO cangivecorrespond-
ing effects
asa suspension
of the solidin contactwith its supernatant
liquor. If a 1% suspension
of ZPTO contains
only0.01% (100ppm)
availablematerialfor epidermalpenetration,
thentheremaining0.99%
dispersed
solidcanbe considered
unavailablefor penetrationinto the
skin. Hence,theoretically,
the clearCarbopolgel that wasprepared
containing
0.01%solubilized
ZPTO canbejustasefficient
a preparation
in relievingseborrheic
dermatitisasan opaquepreparationcontaining
99-foldmore ZPTO assuspended
material. This statementis conjec-
,ture and no attempt hasbeen made to determine its validity either
experimentallyor clinicallyat thistime.
EXPERIMENTAL
The procedurefor determiningsolubilitywasrapid, but only ap-
proximate,sincethe ultimateendof the testingwasnot the elucidation
of solubilitydata,but the formulationof hair products. Thus, 1 g of
ZPTO was dissolved
into 9 g of the amine in questionwith gentle
heating,if necessary.The easewith which the ZPTO wasdissolved
was
notedalongwith the quantityof residualinsolubles
at room tempera-
ture. An estimationof the solubilityof ZPTO in the amine wasthen
made. Besides
ammoniumhydroxide,the following commonlabora-
toryaminesweretestedfor their solventeffecton ZPTO:
triisopropanolamine
triethanolamine
N-methyldiethanolamine
N N-dimethylaminoethanol
N-ethyldiethanolamine
N,N-diethylaminoethanol
Theseamineshaveseveral
characteristics
in common. All aretertiary
amines;they havedifunctionalityin the form of alkanol groupsthat

4. 102 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS
lower
theirbasicity
through
aninductance
effect;
theyareallverypoor
solvents
forZPTO. Otheramines
which
proved
,tobepoorsolvents
were
trilaurylamine,
ethoxylated
cocoamine-15
moles
ETO, andmorpholine.
It wasfoundthat the followingcompounds
containing
primary
aminofunctionalgroups
madeexcellentsolvents:
n-dodecylamine
1,3-diaminopropane
N-(3-aminopropyl)
1,3-propanediamine
N- (3-aminopropyl)N-methyl-
1,3-propanediamine
bis(2-aminoethyl)sulfide
All of theseamineswere capableof dissolving
over 10% ZPTO.
There werealsoa numberof oxyamino
compounds
that showed
very
goodsolventproperties. Thesewere:
ethanolamine
diglycolamine
3-methoxy-n-propyl
amine
3-(2-ethoxyethoxy)-n-propyl
amine
3-[2-(2-e
thoxye
thoxy)e
thoxy]
-n-pro
pylamine
Diglycolamine,*or 2-hydroxy-2'-aminodiethylether,
wassingledout
for its unique solventproperties: it can dissolve42% ZPTO. Of
course, the fact that this amine itself was water soluble was also con-
sideredfavorable. In relationto the ethoxylated
propylamines,
it was
observedthat increasingthe ethoxylationfunction lowerstheir solvent
capacities.Thus, while 3-(2-ethoxyethoxy)-n-propylamine
wasable to
dissolve
over 10% of ZPTO, the solubilitycapacity
of 3-[2-(2-ethoxy-
ethoxy)
ethoxy]-n-propylamine
wasapproximately
8%.
A numberof primaryaminesthatwereexpected
to be goodsolvents
but failed to be were:
N,N-dimethyl-
1,3-propanediam
ine
N-(3-aminopropyl)cyclohexylamine
bis(3-aminopropyl)piperazine
4-(3-aminopropyl)morpholine
ethylenediamine
cyclohexylamine
* JeffersonChemicalCo., Houston,Tex.

5. ZINC PYRITHIONE PREPARATIONS 103
DISCUSSION AND APPLICATION
The solubilityof ZPTO in organicaminesmaybe lookedupon as
the interaction of a Lewis acid and a Lewis base in which the ZPTO,
actingasa Lewisacid,accepts
a pair of electrons
from an aminogroup
thusforming a covalentbond. Zinc is a class
a metal, that is, it is an
electropositive
metalthat formsits moststablecomplexes
with ligands
in whichthe donoratomisnitrogen,oxygen,or fluorine(4). The sta-
bili•tyof theresulting
metalcomplexis a functionof the natureof the
ligand. With classa metals, the greater the base strength of the
ligandthegreateris the tendency
to form stablecomplexes.However,
thiswasfoundnot to be thecase
in all instances.Accordingto dissocia-
tion constanttables,cyclohexylamine,
with a pK• of 10.64,shouldbe
equalto if nota bettersolvent
for ZPTO thandodecylamine
(pK• 10.62)
(5). It wasshownthatcyclohexylamine
wasa considerably
poorersol-
vent than dodecylamine. Ethanolamine,with a relativelylow pK• of
9.50,wascapableof dissolving
ZPTO to over 30%. The high solvency
of ethanolamine
can be explainedthroughchelation. The formation
of a chelatestructureusuallylends itself to stabilizingthe complex,
and the more extensivethe chelation,the more stablethe system. Fig-
ure 2 showsa possiblethree-dimensional
chelatestructure of ethanol-
amine. Observethe formationof a 5-memberedchelatering and note
that the spatialarrangementof the coordinationbondsallowszinc to
be positionedin the center of a tetrahedralstructure (6). However,
2-amino-2-methylpropanol,
whichcanbe thoughtof asa dimethylderiv-
ative of ethanolamine,NHsC (CHa)sCHsOH, is an extremelypoor sol-
vent. This is not surprisingif the sterichindranceof the two methyl
ETHANOLAMINE
Figure 2. ZPTO-ethanolaminecomplex

6. 104 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS
groups
on thecarbonatomalphato theaminofunctionistakeninto ac-
count. Many of the solubilityinconsistencies
in this studycan be ex-
plained by sterichindrance. In general,large bulky ligandsform less
stablemetalcomplexes
thandoanalogous
smallerligands.
Although the moststablemetal chelates
containingsaturatedligands
form 5-memberedchelaterings, saturated6-memberedrings are fre-
quently encountered(7). Figure 3 showsthe 6-rnembered
ring that
1,3-diaminopropane
formswith ZPTO. It isa goodsolvent.
Figure4 shows
the complexformedwhen ZPTO is dissolved
in
N-(3-aminopropyl)-diethanolamine.
Observethat a zincchelatestruc-
ture is formed with the tertiary amino nitrogen atom and an oxygen
Figure 3. ZPTO-1,3-diaminopropane
complex
CH•C
H•0H

7. ZINC PYRITHIONE PREPARATIONS 105
atom of one of the hydroxylgroups. It was concludedthat the pri-
maryaminonitrogenatomdoesnot participatein formingthe chelate
structure. The experimentalproof for this is that when the analogous
compoundwithout hydroxyl groups,N,N-diethyl-l,3-propanediamine,
wastestedfor its solventcapacityon ZPTO, the solubilityof ZPTO was
reducedfrom well over 10% at 20øGto lessthan 1%.
Diglycolamine
The superiorsolventpower of diglycolaminecould be ascribedto
the formationof a tetradentatechelatestructurewith ZPTO (Fig. 5).
•k•
•.,•
..•......
• DIGLY
Figure 5. ZPTO-diglycolamine complex
Diglycolamine,
whichmaybe thoughtof asa derivativeof diethyl ether,
waschosenasthe solubilizing agent for ZPTO in severalclear formula-
tions (Table I). These formulationsare limited by the low water
concentrations
that are required for clarity. Increasingthe concentra-
tion of the water causes
the disruption of the ZPTO-diglycolamine com-
plex permittingfree ZPTO to be thrown out of solution. The proto-
type hair-settinglotion formulation that wasprepared(Table I) con-
tains0.2% ZPTO and isclear. When water isaddedit becomes
cloudy
due to liberated ZPTO. The pH of a 1:1 mixture with water is 8.8.
The shampoo
preparationshownin Table I hasgoodfoamingproper-
tiesdue partly to the high diethanolamide
content. As expected,the

8. 106 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS
Table I
Product FormulationsBasedupon the ZPTO-Diglycolamine Complex
Clear Hair-Setting Lotion
Sequence Ingredient
1 PolyvinylpyrrolidoneK-30
1 Anhydrous ethanol
2 Perfume oil
fZPTO
3 }Diglycolamine
4 3.7% hydrochloricacid
Clear Shampoo
Sequence Ingredient
1 70-30 lauric-myristicdiethanolarnide
1 Isostearic acid
1 Propyleneglycol
fZPTO
2 }Diglycolamine
Hair Gel
Sequence Ingredient
1 Eracol CD-18 a
1 Glycerine
1 Propyleneglycol
1 95% ethanol
J'CarboFol
940
2 •Water
JZeTO
3 }Diglycolamine
Per Cent
2.0
91.7
0.1
0.2
1.8
4.2
Per Cent
23.8
17.0
42.2
1.7
15.3
Per Cent
10 0
10 0
30 0
25 0
0 6075
23 6925
0.07
0.63
Witco Chemical Co., New York, N.Y.
additiono15
waterprecipitates
theZPTO. A 1:1mixtureo15
thisshampoo
with waterhasa pH ot5
9.5.
The hair-groominggel 15ormulation
(Table I), basedupon a poly-
propoxylatedtriol, incorporates
diglycolamineasboth a solubilizer15or
ZPTO and as a neutralizingagent 15or
Carbopolresin. This digly-
colamineneutralizedgelcontains
700 ppm ZPTO and hasa pH of 7.5.
Figure6 isa photograph
that compares
thisgelwith a simpleCarbopol
gel neutralizedwith a system
containing1% ZPTO dissolved
in 28%
ammonium hydroxide. This particular ammonium hydroxide-neu-
tralizedgelcontains
200ppmZPTO and iscloudyat pH 7.6. Actually,
the diglycolamine-neutralized
gel wasinitially clear but a15ter
several
days,small,well-defined
ZPTO crystals
were observed
dispersed
within
it. It appearsthat the re15ractive
index o15
thesecrystals
is closerto the
re15ractive
index o15
the surroundingmedia than the re15ractive
indices

9. ZINC PYRITHIONE PREPARATIONS 107
".•.....•. - ße.!:
... :•dl..::
:.•..
• .• .• .,
•::;';'."' 2-'-
• .•:• :_:.:•::•.':
......... ............
....,.j:;
... . . ..; .:•:-..:-.
:•,:.
......•.-••,..•:•- .... ..
.:Z
:•. "',. '•;•
..... ....•..:
.;• :•:,... •. }.
ß
.:• ,i.' '.• . • ...... :'
' "'•' ' ..•
._. •- .• .&
.--.,-,•?.....::....
:::-;.
::.;.
--:.:.
-....:.:
..:-:;:---.?..:':-:;:..
• •. .'1
.... .. ......
.;;•.•'.•
:. '.,¾i,..:.:.;.;:..•,
,;% ........ :-;• -.•:
.......
•,....
Figure 6. The an:monium hydroxide-Carbopolgel (left) contains200 ppm ZPTO and is
cloudy. The diglycolaminc-Carbopolgel (right) contains700 ppm ZPTO and appearsclear,
due to an optical effect
of thecrystals
andmediain theammoniumhydroxide-Carbopolprepara-
tion, thusmakingthesecrystals
moredifficultto observe. Thesecrystals
will growin sizebut the preparationwill continueto appearclear. By
altering the refractive index of the media the crystalswill be more
visually pronouncedand may give an unusual sparkling effect to the
product. Neither the efficacynor the toxicologicalpropertiesof the
for•nulations outlined in Table I have been determined.
Polyethylenimine
As the searchfor other amino solventsprogressed,
we becamein-
volvedwith a group of aminesthat were decidedlydifferent in their
properties: the polyalkyleniminesand particularly the polyethylen-
imines. This group wasespeciallyattractive in that their higher mo-
lecularweight and bulky molecularstructuremade them relatively in-
vulnerable to subcutaneous
absorption,a particular liability of many
smallerorganicamines(8). Polyethylenimineis madeby the acid-cata-
lyzedpolymerizationof aziridine(Fig. 7). The resultingcationicpoly-
mer, dependingupon polymerizationconditions,can have a molecular
weightashigh as100,000and haveasa composition
a constant
ratio of
25% primaryamineto 50% secondary
amineto 25% tertiaryamine(9).

10. 108 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS
AZIRID•NE H
POLYETHYLENIMINE
(PEI)
œigure7. Acid-catalyzedpolymerizationoœaziridine to form polyethyleneimine
What made this material unusual as comparedto other amineswhich
had beentestedwasthe factthat wateror alcoholwasactuallyrequired
in order to dissolve ZPTO. In effect, we were now able to make clear
preparationsof ZPTO that containedlarge quantitiesof water. Ini-
tially, it wasfound that 1 part ZPTO canbe conveniently
dissolved
in
water using2 parts polyethylenimineof molecularweight 600 (PEI).
The resultingsolution,basedupon a 20% ZPTO concentration,had a
pH of 10.6andcouldbe dilutedto infinitywith waterwithoutcausing
theprecipitation
of ZPTO. It waslaterdeterminedthat 1 part ZPTO
canbe so]ubilizedwith aslittle as 1.35partsPEI. When the pH of an
aqueoussolutioncontaining270 ZPTO and 470 PEI wasloweredby
the slowadditionof 3.7•o hydrochloricacid,a precipitateoccurredbe-
low a pH of 8.8. The precipitate
wasidentifiedasZPTO by infrared
spectroscopy
and wasshownto have the samespectraas the crystals
growingin thediglycolamine-Carbopol
hair dressing.
In a studyof the structureof the complexit wasshownthat the
ultravioletabsorption
spectrum
of a diluteaqueous
solutionof ZPTO
shiftsto onesimilar to sodiumpyrithionewhen aqueous
PEI is added
(10). Since
sodium
pyrithione
is an ionicsaltandhasno coordinate
covalent
metallinkages,
theindicationis,thatthechelate
bonds
within
the ZPTO molecule are broken. From this inference, the solubilization
of ZPTO by aqueous
PEI canbe accounted
for by eitherof two ex-

11. ZINC PYRITHIONE PREPARATIONS 109
Figure 8. Possiblestructuresof solubilizc{ ZPTO in aqueousPEI
planarions. The first (Fig. 8,A) is that a complexis formed with PEI
that is analogousto the tetraammoniazinc complexes. For this to
happen the two coordinationlinkagesthat form the internal chelate
structureof ZPTO would have to open and allow the total of four co-
ordinationlinkagesof zinc to form with PEI. The second
explanation
(Fig. 8,B)is that of a decomposition
of ZPTO into a pyrithionesaltof
PEI and zinc which would be complexedin alkaline PEI media. It•
this is the case,then a solutionof ZPTO in aqueousPEI may exhibit
toxic pharmacologicalproperties similar to sodium pyrithione and
thereforerenderits usein cosmetic
compositions
unacceptable.
To determine the nature of the PEI-solubilized ZPTO, a series of
chromatographic
techniques
wasemployedin whichgel filtration studies
were prominent. Gel filtration, a form of column chromatography,
separates
substances
by molecularweight. The higher the molecular
weight, the more rapidly the substance
is eluted from the column.
ZPTO hasa molecularweightof 318 comparedto approximately600
for the PEI which we used. If the two are not complexedthey should
separate
onthecolumninto twopeaks. It wasfoundthat PEI, zinc,and
pyrithionemigrateasonepeak. This phenomenon
indicates
that the
zinc and the pyrithioneexist in chemicalcombinationin the PEI sys-
tem. This conclusion was also sustained from data obtained from thin-
layerchromatography
studies.

12. 110 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS
Extensive toxicologicalstudiesconfirm the existenceof an intact
ZPTO molecule. A subacute
percutaneous
toxicitystudyon the intact
skinofwhitealbinorabbitswasperformed
with a 2% solubilized
ZPTO
solution,pH 8.8. This 90-daystudyshowed
that ,therewereno demon-
strablesystemic
effects
produced
by therepeated
applicationof theprod-
uct on skin at greatlyexaggerated
levelsof intendedhuman use (11).
Corresponding
tests
with equivalentlevelsof sodiumpyrithionedid pro-
ducesystemic
toxicity.
One of the first formulations prepared containing the ZPTO-PEI
complexwasa clearliquid hair dressing
with a ZPTO concentrationof
0.5% (Table II). This formulation was basedupon an alkoxylated
liquid having hydrophylic-hydrophobic
groupings. Included in the
formulation were natural and syntheticesters,ethoxylatedglycerine,
and other ingredientsthat we thoughtwould contribute to a balanced
hair dressing. The total nonvolatile solidscontent was 20%. It was
decidedtodetermineclinicallyif theZPTO-PEI complexin thisproduct
basewasan effectivetreatmentfor seborrheicdermatitis. Beforedoing
this, the preparationwassubmittedto a seriesof pharmacological
and
toxicologicalteststo which new productsare subjectedin order to
maintain maximum consumersafety. After the safetyof the prepara-
tion had been establishedit was then offered for clinical testing in
Europe. Testswereconducted
concurrently
by dermatologists
in Great
Britain, France,and Italy. The resultsof all thesetestsindicatedthat
the preparationwasdefinitelyeffectivein alleviatingdandruffand, in
manyinstances,
in controlling
eventhemost
severe
cases
(12).
Table II
Clear Liquid Hair Dressing
Sequence Ingredient Per Cent
95% ethanol 71. 697
Ucon fluid mixture a 13.5
Castor oil 2.0
Diisopropyl adipate 0.5
Liponic EG-I• 2.0
UV light absorber 0.05
Perfume oil 0. 313
Water 7.0
'ZPTO 0.5
PEI 1.0
(Water 1.0
3.7% hydrochloric
acid 0.44 (q.s.--pH 8.9)
Union Carbide Chemical Co., New York, N.Y.
Lipo ChemicalsInc., New York, N.Y.

13. ZINC PYRITHIONE PREPARATIONS
Table III
ProductFormulationsBasedupon the ZPTO-PEI Complex
111
Sequence
1
1
1
Sequence
1
1
Sequence
1
1
Clear Shampoo
Ingredient
Sandopan DTC Acid•
Lauric alkanolamide
Water
ZPTO
PEI
Water
Clear Protein Hair Conditioner
Ingredient
Water-soluble protein
Water
ZPTO
PEI
Water
Perfume-hydrotrope
3.7% hydrochloric
acid
Hair-Thickening Lotion
Ingredient
PolyvinylpyrrolidoneK-30
Water
'ZPTO
PEI
Water
'Methocel
resin
b
•Water
3.7% hydrochloric
acid
Per Cent
20.0
3.0
67.0
2.0
4.0
4.0
Per Cent
1.0
97.9
0.2
0.4
0.4
0.1
q.s.--pH 8.8
Per Cent
7.0
40.5
0.5
1.0
1.0
1.0
49.0
q.s.--pH 8.8
SandozChemicalIndustries,Hanover, N.J.
Dow Chemical Co., Midland, Mich.
A series
of prototype
formulations
of otherhair products
waspre-
pared(TableIII). In manycases
theconcentration
levelsof ZPTO are
unrealistically
highin orderto demonstrate
theease
of incorporating
a
largequantityof thecomplex.The clearshampoo
formulation
shown
in Table III contains
Sandopan
DTC Acid whichis an ethoxylated
fattyalcohol
materialhaving,in addition,a carboxylic
acidfunction.
This acid surfactant is used to neutralize some of the excess PEI that
is available
whentheZPTO-PEI complex
is formed. The pH of the
shampoo
maybeaslowas8.8withoutaffecting
clarity. This shampoo
exhibitsgoodfoamingproperties.
In placeof theSandopan
DTC Acidotheracidicsurfactants
maybe
used,
suchasthephosphoric
acidesters
of ethoxylated
fattyalcohols
or

14. 112 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS
the succinicacid half-esters
of fatty amides. The use of ingredients
containingsodiumion shouldbe avoidedbecause
of the possibilityof
hydrolizingthe ZPTO at high pH's and formingthe sodiumpyrithione
in situ.
Other prototypehair preparations
made(Table III) werea collagen-
derivedprotein conditionercontaining0.2% solubilizedZPTO and a
clear hair-thickening lotion basedupon polyvinylpyrollidonethat con-
tained0.5% solubilized
ZPTO. Both of thesepreparations
hada pH of
8.8.
Related Amines Tested
Besidesthe polyethylenimine,
molecularweight 600, usedin the
previousformulations,it wasfound that polyethylenimines
of higher
molecularweightsare alsosuitable. Polyethylenimines,
for example,of
molecular weightsof 1,200, 1,800, and 60,000 were able to solubilize
ZPTO in water. When the polyethylenimine
functionisethoxylated
or
propoxylated,
thusreducingthe primaryaminecontent,the solubilizing
effecton ZPTO is reduced. If a modificationof the polyethylenimine
molecularstructureis madesoasto yield a linear polymericmolecule
composed
of onlysecondary
aminefunctions,
it hasno solubilizing
effect
on ZPTO.
It was found that when the molecular weight of polyethylenimine
is reducedto g00, ZPTO is readily dissolved
without the presence
of
water. Water can still be added to this solution without causingthe
precipitation
of ZPTO. This wastrueof amines
of evenlowermolecu-
lar weightthat may be considered
to be derivedfrom sections
of the
polyethylenimine
molecule. Thus, tris(2-aminoethyl)amine
and tetra-
ethylenepentamine (Fig. 9) showedsimilar behaviorto polyethylen-
TRIS(2-AMINOETHYL)AMINE
TETRAETHYLENE PENTAMINE
Figure9. Formulas
for tris(2-aminoethyl)amine
andtetraethylene
pentamine

15. ZINC PYRITHIONE PREPARATIONS 113
imine of molecularweight300. It isinterestingthat the building block
of these
•nolecules,
ethylenediamine
itself,doesnot dissolve
ZPTO either
with or without water. This is not unusual when one realizes that
ethylenedia•nineis considered
the weakestbaseamongthe polymethyl-
enedia•nines,
NH2(CH2)•NH2, due to its high inductiveeffect,its elec-
trostaticrepulsion effect, and intra•nolecularhydrogenbonding that
shouldgive the ethylenedia•nine
•noleculea •noststable54ne•nbered
cyclicstructure(13).
CONCLUSION
It wasshownthat clearhair preparations
containingZPTO canbe
prepared
by firstcomplexing
theZPTO in a varietyof organicamines.
Its solvation•naybe lookeduponasan acid-base
reactionin which the
solubilityof the ZPTO isa functionof the aminecmnplexant. Among
the factorsthat affectthissolubilityare the basestrengthof the amine,
its sterichindrance,the formation of chelaterings, and its inductance
and electrostaticeffects,all of which contribute to the stability or in-
stabilityof thecomplex. It isshownthat if the properprecautions
are
taken,safeand effectiveclear preparations
can be prepared. What
should be determined is the minionurn concentration of complexed
soluble
ZPTO in suchdear preparations
thatwouldbe effective
against
dandruff.
ACKNOWLEDGMENT
The author would like to acknowledge
and thank the following
individualswhohavecontributedto the findings: Dr. Earle W. Brauer,
Mr. ClydeM. Burnett,Mr. Bernard
L. Kabacoff,
andMr. Radhakrishna
B. Kasat.
(Received
May28, 1971)
REFERENCES
(1) Brauer,
E. W., Opdyke,
D. L., and Burnett,C. M., Antiseborrheic
qualities
of zinc
pyrithione
in a cream
vehicle,
J. Invest.
Dermatol.,
47,174(1966).
(2)ZincandSodium
Compounds
ofOmadine,
Tech.Bull.,OlinChemicals,
NewYork,N.Y.
(g)Opdyke,
D. L., andBurnett,
C. M., Privatecommunication,
RevlonResearch
Center,
Aug. 25, 1965.
(4)Baslo,
F.,andJohnson,
R., Coordination
Chemistry,
W. A. Benjamin,
Inc.,NewYork,
1964,p. 126.
(5)Yukawa,
Y., Handboob
of Organic
Structural
Analysis,
W. A. Benjamin,
Inc.,New
York, 1965,p. 584.

16. 114 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS
(6) Martell, A. E., and Calvin, M., Chemistryo[ the Metal ChelateCompounds,
Prentice-
Hall, Inc.,Englewood
Cliffs,N.J., 1959,p. 254.
(7) Irving, H., Williams, R. J. P., Ferrett, D. J., and Williams, A. E., The influenceof ring
sizeupon the stabilityof metal chelates,
J. Chem.Soc.,1954,p. 3494.
(8) Patty, F. A., Irish, D., and Fasset,D. W., Industrial Hygiene and Toxicology,Vol. II,
Interscience
Publishers,New York, 1963,p. 2037.
(9) PEI--The VersatilePolymer,Tech. Bull., The Dow ChemicalCo.,Midland, Mich.
(10) Kabacoff,B. L., Intern. Rept., Revlon ResearchCenter.
(11) Burnett, C. M., Intern. Rept., Revlon ResearchCenter.
(12) Brauer,E. W., Intern. Rept., Revlon Research
Center.
(13) Gero, A., Inductive effect and hydrogenbonding as factorsin the basestrengthof
polymethylenediamines,
J. Amer.Chem.Soc.,
76,5159(1954).