MXPA01009277A - Iodine preparation compositon - Google Patents

Abstract

An iodine preparation composition suitable for use on wounds comprising an iodide source, an oxidant and a buffer characterised in that the iodide is held separately from the oxidant until the point of use, and that the buffer is capable of maintaining the pH of the composition at between pH 4.5 and pH 6 so that iodine is generated at a physiologically acceptable dose rate.

Description

COMPOSITION OF IODINE PREPARATION DESCRIPTION OF THE INVENTION This invention relates to an antimicrobial composition which can be applied to wounds, scrapes or burns for the prevention or treatment of infections. More particularly, the invention relates to a composition that can provide effective antimicrobial activity and that at the same time avoid irritation of the wound and the skin and delay in the healing of the wound. The antimicrobial materials that are applied topically and the preparations containing them have long been recognized as important parts of the antisepsis of intact skin and wounds. Iodine has been recognized as an antimicrobial agent that is effective against a broad range of microorganisms. However, there are several barriers that prevent the development of an effective antimicrobial composition based on iodine for application to wounds. One of the problems is that iodine tends to react with organic materials found in the wound, different from whites Ref. 133115 intended microbes. This means that iodine, to be effective, needs to be included at high levels such as 0.9% by weight, as described in "Handbook of Wound Dressings," published by Stephen Thomas, 1994, in the Journal of Wound Care. At such levels, and with continued use, iodine could have undesired local side effects such as cell toxicity, hypersensitivity reactions, skin staining and unpleasant odor, and systemic adverse effects such as metabolic acidosis and impaired function. renal. For this reason it is recommended that iodine be applied at levels below 1.35 grams in a week. Another problem is that iodine has a relatively short shelf life when in aqueous solution, which means that any of the compositions that include water need to be prepared just before each application or, again, that the iodine is included. at high levels. This limits the shape of the product. In the past, we tried to solve these problems with iodine using iodophors, which act as release mechanisms for iodine. Iodophors dissociate easily, release iodine complexes with polishers or surfactants. The iodophor compositions are not the most suitable for use in wounds because when applied to a wound, all the iodine present in the composition is readily available for the reaction and therefore the adverse reactions associated with high levels of iodine they are not necessarily avoided. There is therefore a need for a composition that delivers iodine to a wound at a rate that is high enough to provide effective antisepsis but is low enough to avoid the problems of adverse reactions associated with high levels of iodine. GB-B-2276546 for Diversey refers to improved iodophors that are prepared at the time of use. The composition comprises an iodine source, an oxidant and an acid source, the oxidant becoming active only when the composition is dissolved in an aqueous medium. It is said that the composition overcomes the stability problems associated with the production of iodine formulations that are applied by immersion / spray of the teat, which are used for the control of bovine mastitis. The rate at which the necessary iodine is produced for these topical formulations for use on intact skin far exceeds that tolerable for a wound. In these compositions such high levels of iodine are generated that a hydrotrope must be included to prevent the iodine from crystallizing. In addition, iodine has a complex chemistry in aqueous solutions and exists in a number of equilibria. At high concentrations of iodine in the presence of iodide ion there is a strong tendency to the formation of the triiodide ion. It is believed that this ion has little antimicrobial activity but can, however, be absorbed with the risk of systemic intoxication. It has been discovered that it is possible to prepare a composition that can generate iodine at a speed and level that makes it suitable for use in wounds. This is achieved by separating some of the ingredients and controlling the kinetics of iodine production through pH manipulation. Accordingly, the present invention provides a composition for an iodine preparation suitable for use in wounds, comprising a source of iodine, an antioxidant and a buffer solution, characterized in that the oxidant is kept separate from the iodine until such time as it is used, and in that the buffer solution can maintain the pH of the composition between pH 4.5 and pH 6 such that iodine is generated at a physiologically acceptable and effective rate. The invention allows the preparation of compositions that generate a low but effective level of iodine, for example up to about 2,000 μg per gram of composition per hour, preferably in the range of 5 μg per gram of composition per hour up to 1,500 μg per gram. of composition per hour, more preferred in the range of 50 μg per gram of composition per hour up to 1,000 μg per gram of composition per hour so that the amount of free iodine available for antisepsis at any time is at least 0.001% . Preferably, the compositions of the invention are formulated to generate the above iodine levels in a period of about 3 days. In general, the pH of the composition of the invention is below 5.8. It has been found that if the pH is greater than about 6, the rate of iodide production by the reaction of the oxidizing agent with the iodide ions is too low to compensate for any of the losses caused by the reaction of iodide with organic matter. It has been found that in general it is desired that the pH of the compositions is not below 4.5 since otherwise there is a danger that the oxidation rate of the iodide ions will be very fast which results in the composition being It can become toxic. The desired pH of the compositions could be achieved by incorporating pH regulating agents therein. Examples of pH regulating agents that could be included are mixtures of citric acid / disodium phosphate, citric acid / sodium citrate, acetic acid / sodium acetate. Conveniently, the pH regulating agent could be present in an amount of about 2% to 10%, preferably about 4% to 6% by weight and in particular about 5% by weight so that a composition is provided isotonic The amount of oxidizing agent in the composition is chosen such that a stoichiometric equivalence is provided with the iodide. Preferably the oxidizing agent is iodate and is provided in a molar ratio of 1: 5 with the iodide. In this way the iodide present in the composition reacts completely with all the oxidizing agent. To provide the levels and speed of production of iodine in the ranges described above, it is desirable to include up to 2% by weight of iodide, preferably from 0.2% to 2% by weight of iodide. Preferably, iodide and iodate are present as sodium salts, although other common counterions could be used. Suitable forms for administering the compositions include aqueous gels, films, creams, tablets and capsules. The following examples are illustrative of the present invention.

EXAMPLE 1 Gel A Weight in grams Hydroxyethylcellulose 30.00 Propylene glycol 150.00 Na2HP04 35.61 Citric acid 21.01 Potassium iodate 1,124 Water 762,256 Gel B Weight in grams Hydroxyethylcellulose 30.0 Propylene glycol 150.0 Potassium iodide 4.36 Water 815.64 Gel A is prepared by dissolving the pH-regulating salt in a water / propylene glycol mixture and then adding the iodate. When the solution is clear, the hydroxyethylcellulose is added and mixed until the formation of the gel is complete. Gel B is prepared by dissolving the iodide in a water / propylene glycol mixture. Hydroxyethylcellulose is added to this mixture and mixed until the formation of the gel is complete. The gels are packed in separate syringes which are joined by adapting their nozzles to a Y-shaped connector. The contents are sterilized by autoclaving at 121 ° C for 15 minutes. Lowering the plungers simultaneously allows the gels to co-extrude and allows the gels to react while being dispensed to a wound. The co-extrusion of the gels results in a product that produces approximately 100 μg per gram of composition per hour at a pH of about 5.4. The composition causes an annihilation of S. aureus (NCIMB 9518) greater than 5 log which is considered as an acceptable level of antimicrobial activity.

EXAMPLE 2 Film A Grams Hydroxypropyl cellulose 16.0 Propylene glycol 4.0 Potassium iodate 0.1124 Sodium phosphate 1.7805 Citric acid 1.0505 Water 77.0566 Film B Hydroxypropyl cellulose 16.0 Propylene glycol 4.0 Potassium iodide 0.436 Water 79,564 The films are produced by knife-over-roll coating of the aqueous solutions on an inert carrier followed by drying at a temperature not higher than 100 ° C and sterilization by gamma irradiation. The films can be cut into rectangles and added to a wound after which they dissolve in the wound fluid and the reaction is carried out. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is the conventional one for the manufacture of the objects or products to which it refers.

Claims (6)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. A composition for preparation of iodine suitable for use in wounds, comprising a source of iodine, oxidizing agent and a pH regulator, characterized because the iodine is kept separate from the oxidant until the time of use, and that the pH regulator can maintain the pH of the composition between pH 4.5 and pH 6 in such a way that the iodine is generated at a physiologically acceptable rate and dose.
2. 2. A composition for iodine preparation according to claim 1, further characterized in that the composition can generate from 5 μg of iodine per gram of composition per hour up to 1,500 μg of iodine per gram of composition per hour, preferably 100 μg of iodine per gram of composition per hour.
3. 3. An iodine composition according to claim 2, formulated to generate said iodine levels in a period of three days.
4. 4. An iodine composition according to any of the preceding claims, further characterized in that the pH of the composition is maintained between 5.4 and 5.8.
5. 5. An iodine composition according to any of the preceding claims, further characterized in that it includes from 0.2% to 2% by weight of iodine.
6. 6. The use of a composition for iodine preparation according to any of the preceding claims to manufacture a medicament that is used in wounds. 1 . - The use of a composition for iodine preparation according to any of the preceding claims for the treatment of wounds. 8. The use according to claim 6 or 7 for the treatment of sepsis in wounds.