IE42193B1 - Process for the production of iodophors - Google Patents

Abstract

Germicidal complexes of poly-N-vinylpyrrolidone (PVP) with iodine are prepared in the form of granules of virtually uniform composition and particle size. To this end, the following are required: a) a solution and/or colloidal suspension of elemental iodine and of a water-soluble substance which supplies iodide ions, in a first solvent or solvent mixture and b) a solution and/or colloidal solution and/or suspension of PVP in a second solvent or solvent mixture which has different surface tension from the first solvent or solvent mixture. The PVP is at least partially soluble or wettable in the second solvent or solvent mixture. The substances dissolved or suspended in the first solvent or solvent mixture are insoluble or only sparingly soluble in the second solvent or solvent mixture. Component a) is added to component b) in small portions and with uniform mixing. A mixed phase system forms. After further mixing of the multiphase mixture, the iodine/PVP complex-containing agglomerates formed are separated off and dried. By means of the process, which can be carried out continuously, yields of iodophore granules of 75 to 100% can be achieved.

Description

The present invention provides 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 com5 position and particle size, which process comprises (i) producing separately ( (a) a solution an^/or a sol and/or a suspension of elementary iodine and a substance releasing iodide ions in a first water1O miscible solvent or solvent mixture, which may contain up to 20% by weight of water relative to $he first solvent or solvent mixture, and' (b) a solution and/or sol 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, the PVP being at least partially soluble or wettable in, and the substances contained in the first solvent or solvent mixture being insoluble or only slightly soluble in, the said solution and/or sol and/or suspension of PVP; . (3) (ii) combining (a) and (b), with uniform thorough mixing, in small portions to form a mixed-phase system; (iii) continuing the thorough mixing of the multiphase mixture; and (iv) separating and drying the agglomerates which are formed containing the iodine/PVP complex and iodide ions.

A process for producing PVP-Iodophors, i.e. agents containing iodine bound in complex linkage with PVP, is known from USA Patent Specification No. 3,028,300. These agents, which are characterised by a high degree of iodine-complexing, are produced by mechanically mixing together a pulverulent mixture of PVP, elementary iodine and iodide for a period of about 24 hours at room temperature. The degree of iodinecomplexing obtained is expressed by the so-called distribution coefficient (DC) (see columns 2 and 3 of the USA Patent Specification No.3,028,300). Furthermore, it is known from the Belgian Patent Specification No. 814,918 that PVP-Iodophors 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-Iodophor 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 Iodophor constituents, are the iodine loss due to evaporation, the undesirable formation of iodide from iodine, and the impossibility of recovering lost iodine.

A further disadvantage lies in the long duration of mechanical mixing required to effect complexing of the elementary iodine, which applies in particular to the process of the USA Patent Specification No.3,028,300 mentioned - 4 above. The use of spray-dried PVP/iodide preparations as starting material for producing Iodophors 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 with a high proportion of fines. The products 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 2o finely divided solid substances of inorganic nature from liquid suspensions or dispersions by the use of various solvent combinations are already known (see Can.J. Chem.Vol.38 (1960), pages 1911-1916, and OSA 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 pulver30 ulent substances to be granulated are suspended in a liquid system, and then added, with turbulent stirring, to a second liquid solvent or solvent mixture, so that granules are formed. Disadvantages of the aforementioned processes are that they do not permit the incorporation of further constituents into the formed granules nor do 219 3 - 5 they permit the processing of true solutions of the substances to be granulated. Also the production of complexes, especially of Iodophors, cannot be successfully carried out by means of these known processes.

Compared with the known working procedures for the production of PVP-lodophors, the process of the present invention is characterized by simplicity, by a low expenditure on equipment, by high economy in operation and, in particular, by the fact that by this process there are obtained for the first time PVP-lodophors in the form of free-flowing, non-dusty and readily water-soluble granules of practically uniform particle size and of homogeneous composition. The Iodophor granules obtained possess similar advantageous chemical and physicochemical properties to those of the PVP-Iodophor products obtained according to the process of 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 corrosionresistant, 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 Iodophor granulates 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 Θ portions of iodine, iodide (1 ) and PVP can, in addition to the solvents, 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, 4219 3 - 6 separated as required from each other and the constituents are then re-introduced into the circulation system of the process.

In the present process it is necessary, depending on the type of solvent employed and on the temperature, to provide the mixing vessel with a reflux device. The thorough mixing of the multiphase mixture and the addition of the solution, sol or suspension a) to the solution, sol 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 continuously, In the thorough mixing of the multiphase system, e.g.by stirring, care must be taken to avoid the occurrence of shearing forces and of turbulence in the mixture. Otherwise the formation of agglomerates would be prevented or impaired.

The agglomerates are separated from the liquid multiphase system in a manner known per se, e.g.by filtration, and dried at a temperature at which no losses of iodine through evaporation occur.

The process of the invention is preferably performed at room temperature. It has however been shown that it is possible to operate at 0°c and below, as well as up to a temperature of 50°C and above. The possibility of being able to operate within a fairly large temperature range depends largely on the nature of the employed solvent. 4219 3 - 7 Sodium iodide or potassium iodide are preferred as the substances releasing iodide ions. It is however possible to work with any other water-soluble substance releasing iodide ions, including the iodides of lithium, magnesium, calcium, aluminium, ammonium, amines and quaternary ammonium, as well as hydriodic acid.

Solvents suitable for the process of the present invention include solvents of the following classes : alcohols, esters, carboxylic acids, ethers, ketones, ketone alcohols, amides, lactams, amines, hydrocarbons, halogenated hydrocarbons and water. The following are, for example, suitable: 2-diethylaminoethanol, diacetone alcohol, propylene glycol, butanol-(2), methanol, the solvent sold under the registered Trade Mark Frigen, cyclohexane, chloroform, ethyl acetate, cyclohexanol, ethyl formates, citric acid triethyl ester, ethylene glycol, mono-n-butyl ester, butanol-1, benzoic acid benzyl ester, benzyl alcohol, ethylene glycol monoethyl ether, ethanolamine, ethylene glycol monomethyl ether, ethylene glycol, 2-acetoxy-ethanol, ethylenediamine hydrate, diethylacetamide, diethylcarbamate, Ν,Ν-dimethylfbrmamide, 1,2-diethoxyethane, dioctylphthalate, diethylamine, dioxane, dimethylsulphoxide, Ν,Ν-dimethylacetamide, di-iso-propyl ether, dipentenes, n-hexane, hexadecyl alcohol, acetic acid propyl ester, isopropyl chloride, isopropyl palmitate, n-hydroxy-ethyllactamide, 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, propylenecarbon-8-. ate, propargyl alcohol, salicylic'acid ethyl ester, 2,2dimethyl-4-oxymethyl-l,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 is not capable of dissolving, in any significant amount, elementary iodine or the substance releasing iodide ions, such as an alkali metal iodide. On the other hand, the 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 solvent 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 a sol or suspension 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 surface tension that 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, particularly those having 3-9 carbon atoms, and 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 - 9 hydrocarbons, having 1-4 carbon atoms, especially perhalogenated hydrocarbons having 1 or 2 carbon atoms, such as CCl^, CFCly CF^Cl, C2F3C1 or C2i'4Cl2., liquid hydrocarbons having 5-14 carbon atoms, such as n-hexane, cyclohexane, methyIcyclohexane, octane, decane, dipentene, dodecane, tetradecane, aliphatic ethers having 2-8 carbon atoms, such as diethyl ether, tetrahydrofuran, diisopropyl ether, phthalic acid esters such as dibutylphthalate, and trialkylamines such as triethylamine.

With various solvent combinations it can be advantageous 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 from 5000 to 750,000 preferably from 20,000 to 40,000, including the Types K-15, K-30 and K-90 (for the significance of the K-values with regard to molecular weight and viscosity see U S Patent Specification No.2,706,701).

As already mentioned, the present invention gives 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 Iodophor granules, with regard 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. 219 3 -10In general the amounts of iodine and of the substance releasing iodide are so arranged that Iodophor granules are obtained which have a weight ratio of iodide ions Θ (I ) to iodine of 0.2:1 to 5:1, preferably 0.5:1 to 3:1; and a weight ratio of PVP to iodine of 1:1 to 20:1, preferably 3:1 to 5:1.

The process of the invention yields, with established working procedures, PVP-Iodophor granules of practically uniform particle size. By suitable choice of the solvents, of the rate of addition and of the type of dissolved or suspended starting materials, it is possible to obtain granules within a wide range of particles size. The particle size of the granules is preferably 10μ - 3 mm, e.g. 50 - 500 μ.

The following Examples illustrate the invention.

Example 1 A first mixture consisting of a solution of 8 g of elementary iodine and 12 g of 57%, (by weight) hydriodic acid (HI) in 50 ml of ethyl acetate is added dropwise (rate of addition - 5 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 K-30 in 200 ml of cyclohexane. There are formed on the multiphase mixture floating brown agglomerates, which are filtered off by suction and dried for 1.5 hours at 60°C in a vacuum drying chamber. The free-flowing brown Iodophor granules thus obtained have a content of available iodine of 18.9 per cent by weight and exhibit a very high degree of iodine-complexing as well as having good stability. - 11 Example 2 .

The process of Example 1 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 suspension of 25 g of PVP K-30 in 200 ml of cyclohexane. The content of available iodine in the Iodophor granules obtained is 6.3 per cent by weight.

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 fhe 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 Iodophor granules obtained is 9.9 per cent by weight.

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 consists of a suspension of 25 g of PVP K-30 in 200 ml of n-hexane. The content of available iodine in the Iodophor granules obtained is .3 per cent by weight.

Example 5.

The process of Example 1 is repeated with however the modification that the first mixture 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 319 3 - 12 available iodine in the granules produced is 6.1 per cent by weight.

Example 6 The process of Example 1 is repeated with however 5 the modification that 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·.

In Patent Specification No. N we have described and claimed a process for the production of free-flowing granules consisting essentially of θ poly-N-vinylpyrrolidone (PVP) and iodide (I ), the granules being of practically uniform composition and particle size, which process comprises (i) producing separately (a) a solution and/or a sol and/or a suspension releasing iodide ions, in a first watermiscible solvent or solvent mixture, which may contain up to 20% by weight of water, relative to the first solvent or solvent mixture, and (b) a solution and/or sol and/or suspension of PVP in a second solvent or solvent mixture which possesses a surface tension different from that of the first solvent or solvent mixture, the PVP being at least partially soluble or wettable in, and the substance releasing iodide ions which is contained in the first •1219 3 - 13 solvent or solvent mixture being insoluble or only slightly soluble in, the said solution and/or sol and/or suspension of PVP; (ii) combining (a) and (b), with uniform thorough mixing, in small portions to form a mixed-phase system; (iii) continuing the thorough mixing of the multiphase mixture; and (iv) separating and drying the agglomerates containing PVP and iodide which are formed.

Claims (13)

1. Process for the production of germicidally acting complexes (PVP-Iodophors) or poly-N-vinylpyrrolidone (PVP) with iodine, in the form of granules of 5 practically uniform composition and particle size, which process comprises (i) producing separately (a) a solution and/or a sol and/or a suspension of elementary iodine and a substance releasing iodide ions· in a first, water-miscible solvent 10 or solvent mixture, which may contain up to 20% by weight of water relative to the first solvent or solvent mixture, and (b) a solution and/or sol and/or suspension of PVP in a second solvent or solvent mixture 15 which has a surface tension different from that of the first solvent or solvent mixture, the PVP being at least partially soluble or wettable in, and the substances contained in the first solvent or/solvent mixture being 20 insoluble or only slightly soluble in, the said solution and/or sol and/or suspension of PVP; (ii) combining (a) and (b), with uniform thorough mixing, in small portions to form a mixed-phase system; (iii) 25 continuing the thorough mixing of the multiphase mixture; and (iv) separating and drying the agglomerates which are formed containing the iodine/PVP complex and Iodide ions.

2. Process according to Claim 1, in which the substance releasing iodide ions in (a) is sodium or potassium iodide. 4219 3 - 15 3. Process according to Claim 1 in which the substance releasing iodide ions in (a) is hydriodic acid, or the iodide of lithium, magnesium, calcium, aluminium, ammonium, an amine, or quaternary ammonium.

3. 5 4. Process according to any one of Claims 1 to 3, in which an aliphatic alcohol of from 1 to 4 carbon atoms, an aliphatic ketone of from 3 to 9 carbon atoms, or an alkylaeetate in which the alkyl has from 2 to 4 carbon atoms, or a mixture thereof, is employed as the 10 first solvent or solvent mixture. 5. Process according to any one of Claims 1 to 4, in which from 0.5 to 10 per cent by weight of water is present in the said first solvent or solvent mixture.

4. 6. Process according to any one of Claims 1 to 5, 15 in which the PVP employed has a molecular weight of from 5,000 to 750,000.

5. 7. Process according to Claim 6, in which the PVP employed has a molecular weight of from 20,000 to 40,000. 20

6. 8· Process according to any one of Claims 1 to 7, in which a liquid hydrocarbon of from 5 to 14 carbon atoms, an aliphatic ether of from 2 to 8 carbon atoms, a phthalic acid ester, a trialkylamine or a halogenated hydrocarbon of from 1 to 4 carbon atoms, or a mixture 25 thereof, is employed as the second solvent or solvent mixture.

7. 9. Process according to Claim 8, in which a perhalogenated hydrocarbon of 1 or 2 carbon atoms is employed. :2133 -Ιδιο. Process according to Claim 9, in which the perhalogenated hydrocarbon is CCl^, CFC1 3 , CF-jCl, C^F^jCl^j or C 2 F 4 C1 2 . 11. Process according to any one of Claims 1 to 10, 5 in which the proportion of substance releasing iodide ions, and elementary iodine, in (a) and of PVP in (b) is such that granules are obtained having a weight ratio of iodide ions ; iodine of from 0.2:1 to 5:1 and a weight ratio of PVP:iodine of 1:1 to 20:1.

8. 10 12. Process according to Claim 11, in which the proportion of substance releasing iodide ions, and elementary iodine, in (a) and of PVP in (b) is such that granules are obtained having a weight ratio of iodide Θ ions {1 ): iodine of from 0.5:1 to 3:1, and the weight 15 ratio of PVP;iodine is from 3:1 to 5:1. /’

9. 13. Process according to any one of Claims 1 to 12, in which the thorough mixing step (iii) is effected by stirring in such a manner that in the mixture there occurs essentially no shearing/forces and. no turbulence. 20

10. 14. Process according to any one of Claims 1 to 13, in which said process is carried out at room temperature.

11. 15. Process according to any one of Claims 1 to 14, in which the granules obtained have a particle size of from 10 μ to 3 mm. 25

12. 16. Process according to Claim 15, in which the particle size is from 50 to 500 μ.

13. 17. Process according to Claim 1, substantially as described in any one of Examples 1 to 6. 4 219 3 - 17 18. PVP-Iodophors whenever prepared by a process as claimed in any one of Claims 1 to 17.