IE47792B1 - Polypyrrolidone-iodine complex - Google Patents

Description

BACKGROUND OF THE INVENTION T-he iodine complex formed by mixing polyvinylpyrrolidone (PVR) and iodine, first disclosed in U.S.Patent Number 2,739,922 issued to Herman A. Shelanski, has established itself as the preferred way of utilizing the 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 complex 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 possessing medicinal properties similar to the water soluble PVP-iodine complex.

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 iati ng si dc ά ifect s.

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·'.

It is a still further object of this invention to provide - 2 4 7 7 9 2 water insoluble long lasting antiseptic ointments for topical application.

Other objects will be apparent in the detailed disclosure which follows.

DESCRIPTION OF PREFERRED EMBODIMENTS It has been found that polypyrrolidone, also known as nylon-4, a polymer'having the structure ^-(ch2)3-c-1 L.H 0 Jn 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 (fibrils), 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 >4779 2 fibers and for this purpose a polymer having superior thermal stability is required and the molecular weight of the resin becomes important, A molecular weight sufficient to give an inherent viscosity of afleast 2.0 deciliters per gram when measured as a 0.5 gram per deciliter solution in hexafluoroisopropanol 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 are also disclosed in this patent.

The complex of nylon-4 with iodine is best formed by immersing the nylon-4 article in a solution of iodine in aqueous potassium iodide. 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 tirne·^ 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. 7 7 9 2 The iodine complex may be formed by other methods such as exposing the nylon-4 article to iodine vapor or triturating the powdered resin with solid iodine crystals. Alternatively the resin may be ball milled after mixing with iodine crystals to form a powdered complex which is well suited for use as a dry powder or for compounding into an ointment. Other ingredients to minimize caking or to impart additional therapeutic properties may be added to the mixture. For compounding an ointment any suitable ointment base may be used such as lanolin, petrolatum, potassium stearate and many others.

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 brown 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 oh the temperature. The rate is very slow at room temperature but at about 100° C. it is quite rapid. Thus if the complex is placed in boiling water the iodine will be removed completely in a matter of minutes. Similarly 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 however. 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 pH 10. - 5 4 7 7 8 2 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.

In this application 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 the resin must be kept under dry nitrogen in the hopper feeding 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 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 multifiliment structure is preferred. In either case the suture material is 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 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. - 6 4 7 7 9 2 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 invention is not to be limited by the examples cited except as defined in the appended claims.

Claims (11)

1. A composition having microbiological activity comprising a complex of polypyrrolidone and iodine.

2. A composition according to Claim 1 wherein the polypyrrolidone is in the form of a bandage material. 5.

3. , A composition according to Claim 1 wherein the polypyrrolidone is in the form of a suture.

4. A composition according to Claim 1 wherein the polypyrrolidone is in the form of a finely divided powder.

5. A composition according to Claim 1 wherein the poly10. pyrrolidone is. in the form of a film.

6. A composition according to Claim 1 wherein the polypyrrolidone is in the form of fibrils.

7. A composition according to Claim 1 wherein the polypyrrolidone is in the form of a woven fabric. '5.

8. A composition according to Claim 1 wherein the polypyrrolidone is in the form of a non-woven fabric.

9. An ointment comprising a composition according to Claim 1

10. , A biocidal powder comprising a composition according to Claim 1. - 8 4-7792

11. A composition according to Claim 1 wherein the polypyrroiidone is in the form of a molded article.