Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
:~066186
The presen~ invention relates to a novel process
for the production of germicidally acting complexes of
poly~N-vinylpyrrolidone (PVP) with iodine, the material
being in the form of granules of practically uniform
composition and particle size, which process comprises
producing
a) a solution and/or colloidal suspension of elementary
iodine and a substance releasing iodide ions in a
first solvent or solvent mixture, as well as
b) a solution and/or colloidal solution and/or suspension
of PVP in a second solvent or solvent mixture which
has a surface tension different from that of the first
solvent or solvent mixture, and in which PVP is at
least partially soluble or wettable, and in which the
substances dissolved or suspended in the first solvent
or solvent mixture are insoluble or only slightly
soluble;
- combining the solutions or suspensions a) and b), with
uniform thorough mixing, in small portions to thus form
a mixed-phase system; continuing the thorough mixing of the
multiphase mixture; and separating and drying the formed
agglomerates containing the iodine/PVP complex and iodide
ions.
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From the USA Patent Specification No. 3,028,300
there is known a process for producing PVP-Jodophors,
i.e. agents containing iodine bound in complex linkage
with PVP. These agents, which are characterised by a
high degree of iodine-complexing, are produced by
mechanically mixing together a pulverulent mixture of
of PVP, elementary iodine and iodide during a period
of about 24 hours at room temperature. The degree of iodine.
complexing obtained is expressed by the so-called distri-
bution coefficient (DC) (see columns 2 and 3 of the USAPatent Specification No. 3,028,300). Furthermore, it is
known from the Belgian Patent Specification No. 814918
that PVP-Jodophors are produced by starting with a pulverulent
spray-dried mixture of PVP and an iodide, and converting
this mixture by 2- to 3-hours' mechanical mixing with
elementary iodine at room temperature into a PVP-Jodophor
complex, which is a stable, single-phase solid solution
of iodide in PVP with homogeneously distributed iodine
bound in complex linkage.
Disadvantages of the above described processes, which
are based on a mechanical mixing together of the Jodophor
constituents, is the iodine loss due to evaporation, the
undesirable formation of iodide from iodine, and the
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impossibility of recovering lost iodine. A further
disadvantage lies in the long duration of mechanical
mixing to effect complexing of the elementary iodine,
which applies in particular to the process of the USA
Patent Specification No. 3,028,300 mentioned above.
The use of spray-dried PVP/iodide preparations as starting
material for producing Jodophors certainly requires a
shorter mixing time, but an appreciable amount of
equipment is necessary and the spray-dried products exhibit
a fairly wide particle-size distribution wi~h a high
proportion of fines. The products hitherto produced in this
manner display adequate iodine-complexing, but are largely
in the form of pulverulent solids and release more or less a
high amount of dust. Moreover the rate of dissolving of
such pulverulent preparations is, in consequence of the
less favourable wetting property, in many cases too low
for modern requirements in industry, a factor resulting in
loss of time in the production of solutions or in the
necessity for special stirring devices to be used.
In connection with the process according to the present
invention, it is pointed out that working procedures to
effect the agglomeration and separation of finely divided
solid substances of inorganic nature from liquid suspensions
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or dispersions by the use of various solvent combinations
are already known (see Can.J.Chem. Vol. 38 (1960), pages
1911-1916, and USA Patent Specification No. 3,268,071).
The application of multiphase systems with solvents of
varying miscibility for producing soluble granules from
originally finely divided organic substances, such as
dyestuffs and foodstuffs, is described in the German
'Offenlegungsschrift' No. 2,412,369. In this process
the finely divided or pulverulent substances to be
granulated are suspended in a liquid system, and then
added, with turbulent stirring, to a second liquid solvent
or solvent mixture, with the formation of granules resulting.
Disadvantages of the aforementioned processes are that
they do not permit of the incorporation of further
constituents into the formed granules nor do they permit of
the processing of true solutions of the substances to
be granulated. Also the production of complexes, especially
of Jodophors, cannot be successfully carried out by
means of these known processes.
Compared with the hitherto known working procedures
for the production of PVP-Jodophors, the process of the
present invention is characterised by simplici~y, by a
low expenditure for equipment, by high economy in operation
1066186
and, in particular, by the fact that by this process
there are obtained for the first time PVP-Jodophors
in the form of free-flowing, non-dusty and readily
water-soluble granules of practically uniform part;cle
siæe and of homogeneous composition. The Jodophor
granules obtained possess similar advantageous chemical
and physicochemical properties to those of the PVP-
Jodophor products according to the initially mentioned
Belgian Patent Specification No. 814,918. Of particular
advantage is that the present process can be performed
in a very short time, generally within 15 to 30 minutes,
and moreover without the use of expensive equipment, such
as spray dryers or corrosion-resistant, closed mixing
devices. A further advantage of the process of the invention
is that it is not only suitable for batch operation but
that it is also particularly suitable for continuous
operation.
The yields of Jodophor granulate which are attainable
by the process of the invention can be up to 100 per cent
by weight, relative to the total weight of the constituents
used. In general, yields of between 75 and 100 per cent by
weight are obtained. The unreacted portions of iodine,
iodide (J ~ ) and PVP can, in addition to the solvents,
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be easily recovered from the liquid residual mixtures.
Or the residual mixtures in the case of continuous
operation are fed back in a circulation system, separated
as required from each other and the constituents are then
re-introduced into the circulatiorl system of the process.
In the case of the present process it is necessary,
depending on the type of solvent employed and on the
temperature, to provide the mixing vessel with ref]ux
devices. The thorough mixing of the multiphase mixture
and the addition of the solution or suspension a) to the
solution or suspension b) - or inversely is performed
in small portions, e.g. by the dropwise addition, or
injection through a nozzle system, of the portions added.
The rate of addition should be adjusted to ensure that
the formation of the desired agglomerates proceeds con-
tinuously. In the thorough mixing of the multiphase system,
e.g. by stirring, care must be taken to avoid the occ~lrrence
of shearing forces and of turbulence in the mixture. Otherwise
the formatio~ of agglomerates would be prevented or impaired.
The agglomerates are separated from the li~uid multi-
phase syste~ in a manner ~nown per se, e.g. by filtration,
and dried at a temperature at which no losses of iodine
through evaporation occur.
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The process of the inventlon is preferably performed
at room temperature. It has however been shown that it
is possible to operate at 0C and below, as well as up to. a
temperature of 50C and above. The possibility of being able
to operate within a fairly large temperature range
depends largely on the nature of the employed solvent.
Sodium iodide or potassium iodide are preferred as
substances releasing iodide ions. It is however possible
to work with all water-soluble substances releasing iodide
ions, including the iodides of potassium, lithium,
magnesium, calcium, aluminium, ammonium, amines and quaternary
ammonium, as well as hydriodic acid.
As solvents suitable for the process of the present
invention, there may be mentioned representatives having
solvent properties of the following classes of solvents:
alcohols, esters, carboxylic acids, ethers, ketones,
ketone alcohols, amides, lactams, amines, hydrocarbons,
halogenated hydrocarbons and wa~er. The following are, for
example, suitable:
2-diethylaminoethanol, diacetone alcohol, propylene glycol,
butanol (2), methanol, frigen, cyclohexane, chloroform,
ethyl acetate, cyclohexanol, ethyl formiates, citric acid
triethyl ester, ethylene glycol mono-n-butyl ester, butanol 1
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benzoic acid benzyl ester, benzyl alcohol, ethylene glycol
monoethyl ether, ethanolamine, ethylene glycol monomethyl
ether, ethylene glycol, 2-acetoxy-ethanol, ethyl.ene-
diamine hydrate, diethylacetamide, diethylcarbamate,
N,N-dimethylformamide, 1,2-diethoxyethane, dioctylphthalate,
diethylamine, dioxane, dimethylsulphoxide, N,N-dimethyl-
acetamide, di-iso-propyl ether, dipentenes, n-hexane,
hexadecyl alcohol, acetic acid propyl ester, isoprop~,Jl
chloride, isopropyl palmitate, n-hydroxy-ethyl-lactamide,
methanesulphonic acid, methacrylic acid, mesitylene,
methacrylic acid~2-hydroxyethyl ester, morpholine, n-
methylpyrrolidone, aliphatic hydrocarbons, lactic acid
ethyl ester, salicylic acid methyl ester, phthalic acid
dibutyl ester, phenylethyl alcohol, myristinic acid
isopropyl ester, carbon tetrachloride, propylenecarbonat~o,
propargyl alcohol, salicylic acid ethyl ester, 2,2-dimethyl-
4-oxymethyl-1,3-dioxalane, phthalic acid diethyl ester,
2-propyloxy-ethanol or palmitic acid isopropyl ester.
The choice of solvents or solvent mixtures has to be
made on the basis of the requirement that the second solvent
or solvent mixture has not to be capable of dissolving, in any
significant amount, elementary iodine or the substance
releasing iodide ions, such as alkali iodides. On the other hand,
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PVP has to become dissolved, colloidally dissolved, partially
dissolved or at least so well wetted by the second
solvent or solvent mixture that a PVP suspension can
readily form. The first solven~ or solvent mixture should
as far as possible completely dissolve the elementary
iodine and the substance releasing iodide ions. The
process can however also be performed when the elementary
iodine and/or the substance releasing iodide ions are
present as colloidal solutions in the first solvent or
solvent mixture. In order to obtain homogeneous agglomerates
or granules, it is essential that the first solvent or
solvent mixture has a value of surface tension tha~ is
different from that of the second solvent or solvent mixture.
The following solvents are preferably used as the first
solvent or solvent mixture: aliphatic alcohols, especially
those having 1-4 carbon atoms, aliphatic ketones, particu-
larly those having 3-9 carbon atoms, alkylacetates, especially
those having 2 4 carbon atoms in the alkyl group.
The following solvents are preferably used as the second
solvent or solvent mixture: halogenated hydrocarbons having
1-4 carbon atoms, especially perhalogenated hydrocarbons
having 1 or 2 carbon atoms, such as CC14, CFC13, CF3C13,
C2F3C13 or C2F4C12, liquid hydrocarbons having 5-14 carbon
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1066~1B6
atoms, such as n-hexane, cyclohexane, methylcyclohexane,
~ octane, decane, dipentene, dodecane, tetradecane,
a~iphatic ethers having 2-8 carbon atoms, such as
diethyl ether, tetrahydrofuran, diisopropyl ether,
phthalic acid ester such as dibutylphthalate, and
trialkylamines such as tri.ethylamine.
With various solvent combinations it can be advantageoLIs
if the first solvent or solvent mixture contains an
addition of water. The amount of water can be up to 20
per cent by weight, preferably 0.5 - 10 per cent by weight,
relative to the first solvent or solvent mixture.
As PVP-constituent it is possible to use, without
limitation, all available forms which lie within the
molecular-weight range of between about 5000 and 750,000
preferably be,ween 20,000 and 40,000, including the
Types IC-15, K-30 and K~90 (for the signi.ficance of the
K~values with regard to molecular weight and viscosity
see US Patent Specification No. 2,706,701).
As already mentioned, the present invention s
characterised by high yields with respect to the iodine
and iodide used. It is therefore possible without difficulty
to determine beforehand the desired composition of the
final products, i.e. of the Jodophor granules, with regard
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1066i86
to the amounts of iodide and of iodine bound in complex
linkage contained in the final products, by the
appropriate selection of the amounts of PVP, iodine
and iodide in the starting solutions or starting
mixtures. In general, the amounts of iodine
and of the substance releasing iodide is so arranged
that Jodophor granules are obtained which have a weight
ratio of iodide ions (J ~ ) to iodine of 0.2 : 1 to
5 : 1, preferably 0.5 : 1 to 3 : 1; and a wei.ght ratio
of PVP to iodine of 1 : 1 to 20 : 1, preferably 3 : 1
to S : 1.
The process of the invention yields, with established
working procedures, PVP-Jodophor granules of practically
uniform particle size. Ry suitable choice of the solvents7
of the rate of addition and of the type of dissolv~d or
suspended starting materials, it is possible to obtain
granules within a wi.de range of particle size. The
particle size of the granules is preferably 10 lu - 3 mm,
e.g. 50-500 ~.
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Example 1
- A first mixture consisting of a solution of 8 g
of elementary iodine and ]2 g of 57% (by weight) hydriodic
acid (HI) in S0 ml of ethyl acetate is added dropwise
(rate of addition = S ml/min.) at room temperature
with stirring (200 r.p.m.), and with the use of a reflux
device, to a second mixture consisting of a suspension
of 25 g of PVP h-30 în 200 ml of cyclohexane. There are
formed on the multiphase mixture floating bro~n agglom-
erates, which are filtered off by suction and dried for
1.5 hours at 60C in a vacuum drying chamber. The free-
flowing brown Jodophor granules thus obtained have a
content of available iodine of 18.9 per cent by ~eight
and exhibit a very high degree of iodine-complexing as ~ell
as having good stabili.ty.
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Example 2
The process of Example l is repeated with the
modification that the first mixture consists of a solution
of 6 g of elementary iodine and 12.5 g of sodium iodide
in 12.5 g of 96% ethanol and 50 ml of isobutylacetate,
and the second mixture consists of a suspensiorl of
25 g of PVP K-30 in 200 ml of cyclohexane. The content
of available iodine in the Jodophor granules obtained
is 6.3 per cent by weight.
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Example 3
The process of Example 1 is repeated with however
the modification that the first mixture consists of a
solution of 6 g of elementary iodine and 12.5 g of
sodium iodide in 12.5 g of 96% ethanol and 50 ml of
acetone, and the second mixture consists of a suspension
of 25 g of PVP K-30 in 200 ml of C2F3C13. The amount of
available iodine in the Jodophor granules obtained is
9.9 per cent by weight.
.
1066~86
Example 4
The process of Example 1 is repeated with however
the modification that the first mixture consists of a
solution of 6 g of elementary iodine and 12.5 g of
sodium iodide in 12.5% of 96% ethanol and 50 ml of ethyl
acetate, and the second mixture consis~s of a suspension
of 25 g of PVP K-30 in 200 ml of n-hexane. The content
of available iodine in the Jodophor granules obtained
is 10.3 per cent by weight.
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Examele 5
The process of Example 1 is repeated with however
the modification that the first mix~ure consists of a
solution of 2.25 g of elementary iodine and 2.25 g of
potassium iodide in 2.25 g of water, 2.25 g of 96%
ethanol and 18.75 ml of ethyl acetate. The content of
available iodine in the granules produced is 6.1 per
cent by weight.
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Example 6
The process of Example 1 is repeated with however
the modifica~ion tha.t the first mixture consists of a
solution of 5 g of elementary iodine and 5 g of sodium
iodide in 2 g of 96% ethanol, 1 g of water and 30 ml of
acetone, and the second mixture consists of a colloidal
solution or suspension of 20 g of PVP K-30 in 200 ml of
tetrahydrofuran. The content of available iodine in the
granules obtained is 5 per cent by weight.
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