MXPA96005010A - Yodóforo composed of poli-n-vinil-lactama ydextr - Google Patents

Abstract

The present invention relates to an iodophor, comprising: a) from 20 to 71% by weight of PVP or poly-N-vinylcaprolactam, b) from 20 to 71% by weight of saccharified starch from DE 2 to 40, c) from 6 to 25% by weight of elemental iodine, d) from 3 to 12.5% by weight of iodide ions, in which the iodophor is prepared by a process selected from the group consisting of: i) mixing the powdered components of (a) to (d), or mixing the powdered components of (a), (b) and sufficient amount of elemental iodine powder and a reducing agent to provide (c) from 6 to 25% by weight of elemental iodine and d ) from 3 to 12.5% by weight of iodide ions, and heating the mixture from 50 ° to 110 ° C for 3 to 30 hours, ii) heating a solution of (a) to (d), or heating a solution of ( a), (b) and sufficient amount of elemental iodine and a reducing agent to provide (c) from 6 to 25% by weight of elemental iodine and (d) from 3 to 12.5% by weight of iodide ions, from 50% at 100 ° C for 3 to 30 hours, iii) dissolve components (a) and (b) in a minimum amount of water, spray-dry the solution, mix the resulting powder with the powder components of (c) and (d) or dissolve the components (a) and (b) in a minimum amount of water, spray dry the solution, mix the resulting powder with a sufficient amount of elemental iodine powder and a reducing agent to provide (c) from 6 to 25% by weight of the elemental iodine and (d) from the to 12.5% by weight of iodide ions, and heat the mixture from 50§ to 90§C for 3 to 30 hours

Description

YODOPHORO COMPOSED OF POLY-N-VINIL-LACTAMA AND DEXTRINE The present invention relates to an iodophor, which has been improved with respect to the properties of simplicity of preparation, wherein the carrier is composed of a mixture of dextrin with a poly-N-vinyl-lactam, ie the poly -N-vinylpyrrolidone (PVP or polyvidone) or poly-N-vinyl-caprolactam.

In the areas of disinfectants for light services, PVP-iodine is a product that has been established for a long time, but at a high cost. Also, the preparation of iodophors, which contain saccharides, by the polymerization of vinyl pyrrolidone, in the presence of particular oligo- and polysaccharides, is disclosed in EP-A 526 800. Although products of this type are less expensive that PVP-iodine, they do not meet the requirements of this PVP-iodine. In addition, until now, they have not received a pharmacological acceptance.

Patent EP-B 196 813 describes mixtures of PVP-iodine with sugar, EP-A 259 982 with sugar alcohols, with and without sugar, EP-A 213 717 with sugar and a gelling polysaccharide. The preparation is complicated because it is necessary, ideally, to prepare the PVP-iodine and then mix it with one or more additives. Direct mixing of all components is impossible. In addition, the products are not suitable for pharmaceutical purposes, due to their available iodine content, their free iodine content and their iodine loss are, as a rule, outside the range allowed by the health authorities.

US patent 4 719 106 describes mixtures of poly-dextrose-iodine and PVP-iodine. The preparation of the polydextrose in this application is complicated - and not economical: the polysaccharides are broken down to glucose, which is then poly-condensed again in the presence of sorbitol and citric acid (see EP 380 248).

It is an object of the present invention to develop a simple and inexpensive process for preparing an iodophor, which meets the requirements of PVP-iodine in all aspects.

We have found that this object is achieved by converting a mixture of PVP or poly-N-vinylcaprolactam and dextrin with a dextrose equivalent (ED) in the range of 2 to 40, preferably 10 to 30, into the iodine complex, in a conventional way.

Dextrins are commercially available and can be easily obtained from starch by incomplete hydrolysis with a dilute acid, by exposure to heat and by oxidative or enzymatic degradation with amylases.

The products of starch degradation that can be obtained by hydrolysis in aqueous phase and having a weight average molecular weight of 2500 to 25,000 are commonly named saccharified starches, to distinguish them from roast dextrins, and can be obtained commercially as such.

Saccharified starches of this type differ chemically from roasting dextrins, inter alia, by the fact that in a hydrolytic degradation in an aqueous medium (usually suspensions or solutions), which is usually carried out with solids contents of 10 to 30% by weight and preferably with catalysis of acids or enzymes, essentially there is no possibility of recombination and branching, which is also evident, not to a lesser degree, of the different molecular weight distributions. The preparation of saccharified starches is generally known and described, inter alia, in Günther Tegge, StSr e und Starkederivate, Behr's Verlag, Hamburg 1984, pages 173 and 220 et seq., And in patent EP-A 441 197. Saccharified starches which are to be used, according to the invention, are preferably those whose weight average molecular weights Mw, are in the range of 400 to 16,000, particularly preferably in the range of 6500 to 13,000.

The saccharified starches to be used, according to the invention, are normally completely soluble in water, at room temperature, the solubility limit will usually be 50% by weight. Preferably, solutions of 10-20% by weight, particularly preferably solutions of 30 to 40% by weight, are clear and not colloidal suspensions at room temperature. It is also advisable to use, according to the invention, those saccharified starches having an ED dextrose equivalent of from 2 to 40, preferably from 10 to 30 and particularly preferred from 10 to 20. The ED is characterized by the reducing capacity, with based on the reducing capacity of anhydrous dextrose, and is determined by the method of DIN 10 308, Edition 5.71, of the Deutscher Normenausschuss LeJejisjnittel und landwirtschaftliche Produkte, (see also G? nther Tegge, Stá 'rke und Stárkederivate, Behr's Verlag , Hamburg 1984, page 305).

Suitable starches as starting materials for the preparation of saccharified starches to be used according to the invention are, in principle, all native starches, such as cereal starches (for example corn, wheat, rice or millet), the starches of tubers and roots (for example the potato, cassava roots or maranta) or starches of sago.

A considerable advantage of the saccharified starches to be used, according to the invention, is that no further chemical modification is required for their preparation of use, apart from the partial hydrolysis of the starch starting material, which can be carried performed in an extremely simple way. The saccharified starches, used in the examples, are the products C * PUR 01906, 01908, 01910, 01915, 01921, 01924, 01932 or 01934 of Cerestar Deutschland GmbH, of Krefeld. Essentially all of them have a bimodal molecular weight distribution and have the following characteristics: Determinations of Mn by vapor pressure osmosis gave the following values for the preferred types, 01910 and 01915: 1560 g / mol (1910) 980 g / mol (1915) H = heterogeneity Mw = weight average molecular weight Mn = molecular weight number average ED = dextrose equivalent.

For the reaction of iodine and iodide with the carrier in the solid state, it is necessary that this carrier be homogeneous. This homogeneity can be achieved by drying the solution of all the components, but it is also sufficient to grind the components together to a powder. This can take place by conventional techniques, for example with ball mills, intensive mixers, cylinder mixers with balls, etc. The iodine and reducing agent or iodide can subsequently be mixed as a solid or solution in the same vessel. Complexes formed by adding sufficient iodine and iodide in the final mixture will contain from 6 to 25, preferably from 15 to 20,% by weight of iodide and 1 mole of iodide per mole of iodine (I2), and subsequent heating to 50-ll? Ac for several hours. Any cation is suitable for iodide, usually sodium or potassium. This iodide can be replaced by an equivalent amount of an agent which reduces iodine to iodide, for example, formic acid and its salts, preferably the ammonium, glucose, ascorbic acid, malonic acid, oxalic acid, ammonium oxalate. , urea, urea-H2? 2, or ammonium carbamate, if the initial amount of iodine is correspondingly increased. The quantity must also be taken from the fact that dextrins have, due to their aldehydic end groups, some ability to reduce iodine.

The complete mixture can, if it is in the form of a solution (preferably in water) be sold and used in this way. However, iodophors are usually prepared and sold in powder form. They can be used as light duty disinfectants, also in the form of powder or in aqueous solution. In any case, the action begins only in solution and it is thus necessary in the dry application that at least some moisture is present in any form (for example discharge of wounds or medical use). The iodophor can also be incorporated and used in the form of creams, sprays or others, such as suppositories. The contents by weight of the complete mixture (based on the solids content, in the case of a solution) are 20-71, preferably 30-60,% PVP or the poly-N-vinylcaprolactam, 20-71, preferably 30-60,% dextrin, 9-37.5% iodine, of which one third is, in each case, in the form of iodide ions, and 0-900, preferably 0-500,% water.

Polymeric vinyl lactams have K values determined by the method of H. Fikentscher (Cellulosechemie 13 (1932), 58-64 and 71-74) in the range of 12 to 100, preferably 25 to 70. The interlaced PVP can also be used to prepare the solid iodophor and can react with the starches that are insoluble in water, to give an iodine complex and thus be used, for example, in the application to wounds. The available iodine content was determined by the method of Deutscher Arzneimittel Codex (DAC) 1986, 22 Supplement 1990, for polyvinyl-iodine. The content specified there is a minimum of 9 and a maximum of 12% of available iodine. The same applies to USP XXII (polyvidone-iodine), which also describes the determination of iodine content. This available iodine content corresponds to the value measured by the titration against thiosulfate. The content of free iodine was determined by the method of D. Horn and. Ditter, PVP-Iod in der operativen Medizin, pages 7 et seq., Springer-Verlag, Heidelberg 1984.

The total loss of weight when drying in an oven to 100-1052C (loss of drying) is also fixed in the 1986 DAC, 3rd part 1988, to a minimum of 8% in 0.5 g of substance, and the products, according to the invention, are fulfilled with this.

The loss of available iodine (loss of iodine) in storage at elevated temperature gives information about the stability of the complex and is determined as follows: The determination is carried out in a PVP-iodine solution, which contains 1% available iodine. This is prepared as follows: x g of the PVP-iodine sample was weighed in an Erlenmeyer flask with obturator and brought to a total weight of 50 g with water.

The calculation of the quantity x in grams to be weighed is: 5000 x = (100 - LD) X AI LD =% loss on drying (DAC method) AI =% available iodine (DAC method) The solution was shaken for 3 hours.

After shaking, 5.0 ml were pipetted with a calibrated bulb pipette into a 250 ml Erlenmeyer flask. were diluted with 100 ml of distilled water and 1 drop of acetic acid and titrated against a 0.02N solution of sodium thiosulfate, as quickly as possible, to the end point (colorless or pale yellow) (V used).

Storage at high temperature.

A dark bottle of 25 ml with obturator was filled to 1 cm. under the obturator, with a solution of PVP-iodine and then stored in an oven at 80 ± 0.52c for 15 hours. The bottle was briefly ventilated by removing the plug for about 15 minutes after the introduction into the oven. After storage for 15 hours and after cooling the contents of the bottle, 5.0 ml was removed, and the available iodine content was determined as described in DAC, with a 0.02N solution of sodium thiosulfate. (N used).

Calculation of iodine loss V - N% iodine loss = 100 V where: V = ml of the Na2S2Ü3 solution used before storage N = ml of the Na2S2? 3 solution used after storage.

Note: In order to be able to detect irregularities (temperature fluctuations, current failures, etc.) during storage it is also necessary to analyze a comparative sample with a known loss of iodine.

Dextrins, by themselves, are incapable of forming sufficiently stable iodine complexes. However, surprisingly, they are capable when mixed with PVP or poly-N-vinylcaprolactam, since equal amounts of the mixture, on the one hand, and the PVO or unmixed poly-N-vinylcaprolactam, on the other, take identical amounts of iodine with the same binding power. There is obviously a kind of synergism in the mix. In contrast to the graft copolymers, the mixtures are pharmacologically acceptable products. In comparison with the PVP-iodine, the iodophors, according to the invention, not only have ecological advantages, based on the good biodegradability of the dextrin content, but also have economic advantages because the costs of the starting material are greatly reduced . Furthermore, the iodophors, according to the invention, surprisingly, in contrast to those known with different (poly) saccharides, usually comply in all respects with the requirements of the approved regulations and practice, as shown in the following table. : Comparison between the PVP-dextrin-iodine, according to the invention, and other adducts of PVP-polysaccharide-iodine *) K. Zulkowsky, Ber. d. Deutschen Chem. Ges. 18 (1980), 1395 Since the diluents, previously described, for PVP-iodine, that is, sugars, sugar alcohols and polysaccharides that form gels, like high-cost polydextrose, do not provide a satisfactory solution for not complying with the approval regulations of drugs, it was not expected that the simplest industrial solution, according to the invention, could provide better results. The invention thus provides, in a surprisingly simple manner, novel iodophors that are lower in cost than PVP-iodine and technically at least equivalent to them.

E J EMP L O S 1. A mixture of equal parts by weight of dextrin, with an ED of 17.5 to 19, and polyvinylpyrrolidone (K = 30) was mixed with 1.5% ammonium format and 17% iodine, based on the polymer content, a mixer, initially at room temperature, for 1 hour, and then at 7 ° C for 20 hours. The solids content of the powder was 95.8%, the available iodine content was 11.7%, the iodine loss was 2.6%, the free iodine content was 3.0 ppm and the iodide content was 5.3%.

A mixture of equal parts of dextrin with an ED of 17.5 to 19, and polyvinylpyrrolidone (K = 30), was mixed with 1.5% ammonium formate and 17% iodine, based on the polymer content, in a mixer , initially at room temperature, for 1 hour, and then at 80 C for 8 hours. The solids content of the powder was 97.0%, the available iodine content was 12.0%, the iodine loss was 1.5%, the free iodine content was 2.6 ppm and the iodide content was 4.7%.

A mixture of equal parts of dextrin with an ED of 13, and polyvinylpyrrolidone (K = 30), was mixed with 1.5% ammonium format and 17% iodine, based on the polymer content, in a mixer, initially at ambient temperature, for 1 hour, and then at 70SC for 20 hours. The solids content of the powder was 96.8%, the available iodine content was 10.7%, the iodine loss was 3.0%, the free iodine content was 3.0 ppm and the iodide content was 5.9.

A mixture of equal parts of dextrin with an ED of 10 and polyvinylpyrrolidone (K = 30), was mixed with 1.5% ammonium format and 17% iodine, based on the polymer content, in a mixer, initially at the ambient temperature, for 1 hour, and then at 80 C for 8 hours. The solids content of the powder was 96.5%, the available iodine content was 11.3%, the iodine loss was 2.5%, the free iodine content was 3 ppm and the iodide content was 5.6%. A solution of equal parts dextrin with an ED of 10 and the polyvinylpyrrolidone (K = 30) was mixed with 1.5% formic acid and spray dried. Next, 15% iodine was added and the powder was mixed at room temperature for 1 hour, and then at 70 C for 20 hours. The solids content of the powder was 96.5%, the available iodine content was 10.8%, the iodine loss was 4%, the free iodine content was 2.5 ppm and the iodide content was 6.0%.

A mixture of dextrin with an ED of 17.5 to 19, and polyvinylpyrrolidone (K = 30) in a ratio of 1.25: 1 by weight, was mixed with 1.5% of ammonium format and 17% of iodine, based on the content of the polymer, in a mixer, initially at room temperature, for 1 hour, and then at 80 ° C for 9 hours. The solids content of the powder was 95.0%, the available iodine content was 11.9%, the iodine loss was 3.3%, the free iodine content was 3.2 ppm and the iodide content was 4.9%.

A mixture of dextrin with an ED of 17.5 to 19, and polyvinylpyrrolidone (K = 60) in a ratio of 1.5: 1, was mixed with 1.5% ammonium format and 17% iodine, based on the polymer content , in a mixer, initially at room temperature, for 2 hours, and then at 802C for 8 hours. The solids content of the powder was 95.6%, the available iodine content was 11.5%, the iodine loss was 1.6%, the free iodine content was 1.5 ppm and the iodide content was 5.9%. A mixture of dextrin with an ED of 17.5 to 19, and polyvinylpyrrolidone (K = 30) in a ratio of 2: 1, was mixed with 1.5% ammonium format and 17% iodine, based on the polymer content , in a mixer, initially at room temperature, for 2 hours, and then at 802C for 8 hours. The solids content of the powder was 94.9%, the content of the available iodine was 11.8%, the loss of iodine was 1.6%, the content of free iodine was 5 ppm and the iodide content was 5%. A mixture of dextrin with an ED of 17.5 to 19, and polyvinylpyrrolidone (K = 32) in a ratio of 1: 1, was mixed with 1% ammonium format and 15% iodine, based on the polymer content , in a mixer, initially at room temperature, for 1 hour, and then at 902C for 8 hours. The solids content of the powder was 96.0%, the available iodine content was 10.1%, the iodine loss was 1.7%, the free iodine content was 5.9 ppm and the iodide content was 4.7%.

Claims (6)

1. An iodophor, which comprises: a) from 20 to 71% by weight of the PVP or poly-N-vinylcaprolactam; b) from 20 to 71% by weight of dextrin with an equivalent of dextrose from 2 to 40; c) from 6 to 25% by weight of elemental iodine; d) from 3 to 12% by weight of iodide ions.

2. A liquid iodophor, composed of 0.1 to 40% of an aqueous solution of an iodophor intensity, as claimed in claim 1.

3. An iodophor, as claimed in claims 1 or 2, wherein the dextrin has a dextrose equivalent of 10 to 30.

4. A process for preparing iodophors, as claimed in claim 1, by mixing the powder components (a) to (d), or, instead of the iodide ions (d), an equivalent amount of a reducing agent , and heat the mixture to a temperature of 50-1102C for 3 to 30 hours.

5. A process for preparing iodophors, as claimed in claim 2, by heating a solution of components (a) to (d) together, or, in place of the iodide ions (d), an equivalent amount of a reducing agent, at a temperature of 50 to 1002C, for 3 to 30 hours.

6. A process for preparing iodophors, as claimed in claim 1, by dissolving components (a) and (b) in the minimum amount of water, spray drying the solution, mixing the resulting powder with the powder components ( c) and (d), or, in place of the iodide ions (d9, an equivalent amount of a reducing agent, and heating the mixture at a temperature of 50 to 90 C, for 3 to 30 hours.