Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
11197~8
POLYPYKROLI~ONE-IODINE COMPLEX
BACKGROUND O~ THE IN~ENTI~N
The iodine complex formed by mixing polyvinylpyrrolidone
(PVP) and iodine, first disclosed in U.S. Patent Number 2,739,922
issued to Herrnan A. ~helanski, has established itself as the
preferred way of utilizing ~he desirable biocidal properties of
iodine while avoiding the irritating side effects. It has become
the product of choice especially in surgery where it is used to
coat the skin prior to incision.
PVP is a water soluble polymer and likewise the PVP-iodine
cpmplex is water soluble. There are applications however in which
this solubility in water is undesirable. For example, in topical
applications the effectiveness of a water soluble antiseptic is of
short duration since it is readily washed away not only by water
but by perspiration. A water insoluble complex with iodine which
exhibits similar "tamed iodine" properties would be much more
; permanent.
OBJECTS OF THE INVENTION
It is a primary object of this invention to provide a water
insoluble and therefore more permanent complex of iodine possess-
ing medicinal properties similar to the water soluble PVP-iodine
complex.
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It is another object of this invention to provide a water
insoluble complex of iodine which slowly releases elemental iodine
in small but effective amounts over a long period of time thus
prolonging the microbiological activity while minimizing the
irri~ating side effects.
It is a further object of the invention to provide a novel
bandage and suture material which in itself is the bactericidal
and fungicidal agent.
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It is a still further object of this invention ~o provide
water insoluble long lasting antiseptic ointments for topical
application.
Other objects will be apparent in the detailed disclosure
which fol]ows.
DESCRIPTION_OF PREFERRED EMBODIMENTS
It has been found that polypyrrolidone, also known as
nylon-4, a polymer having the structure
~ (CH2)3-~
can be made to form a complex with elemental iodine which is very
similar to the polyvinylpyrrolidone-iodine complex. Unlike the
PVP-iodine complex, however, the nylon 4-iodine complex is not
soluble in water.
It is surprising and unexpected that nylon-4 should form a
complex with iodine since the pyrrolidone ring, which is intact in
PVP, is opened and non-existent in nylon-4 which has instead a
polyamide structure. Nevertheless it has been found that a
complex with iodine will form and furthermore it closely resembles
" the PVP-iodine complex except for the lack of solubility in water.
The polypyrrolidone employed to make the iodine complex may
be in any physical form such as the powdered resin, a pulp
tfibrils), an extruded rod or filament, a fabric woven from a
textile fiber, a film or a molded article. For purposes of making
an ointment the finely powdered resin is used and the molecular
weight (i.e. the value of n in the above formula) is unimportant.
But for making sutures or bandages from woven fabric it is
necessary to melt extrude the resin to form the filaments or
~119748
fibers and for this purpose a polymer having superior thermal
~ stability is required and the molecular weight of the resin
,`d becomes important. A molecular weight sufficient to give an
` inherent viscosity of at least 2.0 deciliters per gram when
, measured as a 0.5 gram per deciliter solution in hexafluoroiso-
propanol at 25 C. is needed. Most preferably resins having an
inherent viscosity of from 3.0 to 4.0 or higher are used for melt
spinning purposes. Methods of making polymers of 2-pyrrolidone
having these characteristics are disclosed in U.S. Patent number
3,721,652. The methods of determining the inherent viscosity
5':,' are also disclosed in this patent.
The complex of polypyrrolidone and iodine is formed by
reacting polypyrrolidone with iodine. A preferred formula is
,
Potassium iodide 3.3 grams
Water 100 ml
Iodine 2.0 grams
Upon immersion in this solution the white polypyrrolidone article
turns to a dark chocolate-brown color almost immediately and then
becomes black. Upon drying the color becomes lighter. Immersion
times range from a few seconds to two or three minutes. Shorter
immersion times will produce a golden yellow color in the dried
article while longer times will give a dark brown color in the
dried material. The color of the dried complex is a measure of
the amount of iodine present. Excessive amounts of iodine will
tend to degrade the polymer and should be avoided if this is
important as it is in a textile fiber.
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~ ~ iO(~illC C(.~ `X III<Iy ~)~` t()l~ C`(I ~)y ~ r ~ ;U~}~
cxl)c;~ ?, Ihe tlylo~ rticlc to ioclirle val-or or tritur-atirlg th~
powderecl res;n ~ith ~solid iodirle crya~clls~ Al~errl~ltively t~le
resin may be ball milled af-~er mixing with iodine crystals to
form a powdered complex which is well suited for use as a dry
powder for compounding into an ointment. Other ingredients
to minimi~e cak;ng or to impart additional therapeutic properties
may be added to the mixture. For compound;ng an ointment any
suitable ointment base may be used such as lanolint petrolatum,
10 potassium stearate and rnany o-thers.
The iodine is rather tightly held in the complex. By way
of comparison, if cotton (another hydrophyllic fiber) is immersed
in an iodine solution prepared according to the recipe given above
it develops a similar dark brown color. But the iodine is only
held mechanically and washes out completely with water within a
minute. The dark bro~n complex formed with nylon-4 does not
readily wash out with water. Small amounts of iodine are released
however at a rate which is dependent on the temperature. The rate
is very slow at room temperature but at about 100 C. it is quite
20 rapid. Thus if the complex is placed in boiling water the iodine
- will be removed completely in a matter of minutes. Sirnilarly if
placed in an oven at 100 C. the iodine will sublime out of the
complex very rapidly leaving colorless nylon-4. Samples may be
kept for several months at room temperature without appreciable
loss of iodine howeverO At 40 C. no appreciable loss of iodine
occurs within 24 hours. Also the complex is quite insensitive to
changes in pH. No loss in iodine content (such as to iodide ion)
occurs within a range of pH 5 to pll 10.
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In order to be effective a slow release of iodine must occur
and at body temperature this release takes place at about the
proper rate. For many reasons a bandage should be changed every
24 hours but it should remain effective during this period of
time. An important feature of the nylon 4-iodine complex is that,
` unlike its PVP-iodine counterpart, if the bandage or other dressing
gets wet even from perspiration the biocidal agent is not washed
away.
Another embodiment of the invention is a biocidal suture.
10 In this appliaction the polypyrrolidone resin is melt extruded
at temperatures of about 290 C. under high pressure generated by
; the screw of the extruder. Care must be taken to dry the resin to
~ not more than about 0.03% moisture content before extruding and
,i', the resin must be kept under dry nitrogen in the hopper f~eding
~,' the extruder to prevent further moisture pick-up.
'~' The molten resin is forced through a spinnerette consisting
of a single hole to form a monofilament or multiple holes to form
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a textile fiber. The size of the hole and the amount of draw
~'~ determine the diameter of the filament or filaments as well as the
20 tensile strength. For certain applications a multifilament
1 structure is preferred. In either case the suture material is
,1 then passed through an iodine bath made according to the recipe
given earlier.~The residence time in the bath may be from a few
seconds to a few minutes depending upon the amount of iodine
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, desired in the complex. The material is then washed briefly in
, water then air dried.
' For bandage applications a suitable fabric is woven from
nylon-4 textile fiber and treated in the iodine bath in a similar
manner.
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The nylon 4-iodine complex may be utilized in many other
ways, for example as an inner layer in packaging to serve as a
biocidal barrier thus keeping the contents of the package sterile
or as a source of a low concentration of iodine vapor to provide
a sterile atmosphere. Since there are many different embodiments
of this invention which may be made without departing from the
spirit and scope thereof, it is to be understood that the inven-
tion îs not to be limited by the examples cited except as defined
in the appended claims.
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SUPPLEMENTARY DISCLOSURE
The complex of nylon-4 with iodine is best formed by
immersing the nylon-4 article in a solution of iodine in an
aqueous solution of an inorganic iodide. A preferred formula
i s:
Potassium iodide 3.3 grams
Water 100 ml
Iodine 2.0 grams
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but sodium, lithium, calcium, magnesium, etc. iodides may
also be used. Any water soluble iodide which forms iodide
ions in water solution is satisfactory provided the I3-ion
; is formed when iodine is added.
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