Method for producing polyvinylpyrrolidone-iodine complex

Abstract

To provide a method for producing a polyvinyl pyrrolidone-iodine complex that satisfies all the specifications in the pharmacopoeial standards of various countries, offering high quality and stability.SOLUTION: A method for producing a polyvinyl pyrrolidone-iodine complex includes mixing polyvinyl pyrrolidone with iodine in a solid-phase state and then adding hydrogen iodide for a reaction.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a method for producing a polyvinylpyrrolidone-iodine complex. [Background technology]

[0002] Polyvinylpyrrolidone-iodine complex (hereinafter referred to as "PVP-I"), also known as povidone-iodine, is an iodine complex formed by combining polyvinylpyrrolidone (hereinafter referred to as "PVP") with iodine. PVP-I is commercially available as a brown powder product that dissolves in water, ethanol, etc., and its aqueous solution is widely used as a bactericide or disinfectant. The bactericidal or disinfecting action of PVP-I is thought to be exerted by the gradual release of iodine (I2) that is incorporated into PVP to form a complex, and its oxidizing effect inhibits membrane function by oxidizing the amino acids that make up the membrane proteins on the surface of microorganisms.

[0003] The following methods have been proposed as conventional methods for producing PVP-I. (1) A method in which hydrogen iodide gas or an alkali metal iodide salt is added to an aqueous solution of PVP, the solution is dried, and the resulting powdered PVP-iodide mixture is reacted with iodine (Patent Document 1). (2) A method in which powdered PVP obtained by polymerization in an anhydrous organic solvent in the presence of a specific initiator is mixed with powdered iodine at room temperature (Patent Document 2). (3) A method in which PVP and iodine are reacted in an aqueous solution in the presence of formic acid, oxalic acid, or carbonic acid, or an ammonium salt of formic acid or oxalic acid (Patent Document 3). (4) A method in which powdered PVP is mixed with iodine and then heat-treated (Patent Document 4). (5) A method of reacting hydrogenated PVP with iodine in a solid phase (Patent Document 5). (6) A method in which PVP having a specific water content is used and heated together with iodine (Patent Document 6). (7) A method in which dry PVP powder, iodine powder, and an iodide selected from hydrogen iodide gas and alkali metal iodide salts are mixed in a specific ratio at room temperature for 24 hours (Patent Document 7). (8) A method of reacting powdered PVP with iodine in the presence of formic acid, oxalic acid or carbonic acid, or an ammonium salt or amide of formic acid or oxalic acid at 70 to 100° C. in a solid phase (Patent Document 8). (9) A method in which powdered PVP is contacted with HCl gas to form a (PVP)2HCl complex, which is then reacted with iodine to obtain a water-soluble PVP / HCl / I2 complex (Patent Document 9). (10) A method in which a PVP aqueous solution of a specific concentration is mixed with iodine and heated at 50 to 110°C for 30 minutes to 15 hours in the presence of a reducing agent selected from formic acid, oxalic acid, and their esters, salts, or amides (Patent Document 10). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Publication No. 50-035318 [Patent Document 2] Japanese Patent Application Publication No. 51-046393 [Patent Document 3] Japanese Patent Application Publication No. 56-065006 [Patent Document 4] German Patent No. 1037075 [Patent Document 5] Japanese Patent Application Publication No. 56-061405 [Patent Document 6] U.S. Patent No. 2,900,305 [Patent Document 7] U.S. Patent No. 3,028,300 [Patent Document 8] Japanese Patent Application Publication No. 54-143495 [Patent Document 9] Special Publication No. 5-502660 [Patent Document 10] Special Publication No. 2003-509347 Summary of the Invention [Problem to be solved by the invention]

[0005] In the method of Patent Document 1, iodide (I - When hydrogen iodide gas is added as a solvent, it becomes hydroiodic acid, which is a strong acid in aqueous solution, and this causes a problem of strong corrosiveness in the drying process. - When an alkali metal iodide salt such as sodium iodide is added as an additive, there is a problem that the ash content of the PVP-I product increases. The method of Patent Document 2 is said to be suitable for producing PVP-I with excellent stability, but requires heating (heat treatment) at 90 to 95°C for 10 hours or more. The method of Patent Document 3 also requires a long reaction time of 7 to 32 hours. The method of Patent Document 4 also requires heat treatment at 90 to 100°C for 18 to 64 hours, the method of Patent Document 5 also requires heating at room temperature for 5 hours and then at 90°C for 20 hours, and the method of Patent Document 6 also requires heating at 95°C for 22 hours. When heating is performed for such a long time or PVP with a high water content is used, the product becomes lumpy and the PVP is prone to burning, which causes problems in terms of workability and quality. In the method of Patent Document 7, although the heat treatment is omitted, impurities with a strong iodine odor are produced, and the ash content in the product is also a problem. The method of Patent Document 8 can shorten the heat treatment time, but when the obtained PVP-I is dissolved in water, iodine is liberated in a short time, limiting the storage period. The product obtained by the method of Patent Document 9 has a low partition coefficient of less than 20, and has a problem with storage stability. In the method of Patent Document 10, the amount of ash in the product is an issue, and in addition, when powdered or granular PVP-I is obtained, water must be removed.

[0006] On the other hand, PVP-I is generally commercially available as a brown powder containing available iodine, i.e., active iodine and iodide that can be titrated with sodium thiosulfate. Indices for evaluating the quality of PVP-I include the "distribution coefficient (DC)" and "iodine loss" disclosed in the 18th Edition of the Japanese Pharmacopoeia and Patent Document 7, etc. The "distribution coefficient" is calculated from the amount of iodine (I2) extracted when an aqueous solution of PVP-I is extracted with heptane. If the distribution coefficient is 200 or more, it means that the amount of iodine simply attached to the PVP surface is small, and a large amount of iodine is taken up into the PVP to form a complex. "Iodine loss" is also called accelerated stability test, in which the amount of available iodine in an aqueous solution of PVP-I at room temperature and the amount of available iodine in the aqueous solution after heating at a specified temperature for a specified time are measured, and the difference is evaluated. In other words, it is an index of the stability of PVP-I in an aqueous solution, and if the difference is 6% or less, it means that the time it takes for free iodine to be released (liberated) from PVP into the aqueous solution is slow, and the stability of PVP-I is good. In addition to the problems mentioned above, the methods of Patent Documents 1 to 10 have the problem that it is difficult for the obtained PVP-I to satisfy all the items related to the above-mentioned quality evaluation indexes.

[0007] The present inventors have investigated a method for easily producing PVP-I that satisfies all the quality evaluation indexes. As a result, they have found that high-quality and stable PVP-I that satisfies the quality evaluation indexes such as the distribution coefficient and iodine loss as well as the Japanese Pharmacopoeia can be produced by previously mixing PVP and iodine in a solid phase, then adding hydrogen iodide as an iodine source to this mixture, and mixing in the solid phase, preferably under heating, and thus completing the present invention. An object of the present invention is to provide a method for producing a polyvinylpyrrolidone-iodine complex, which satisfies all the specifications of the pharmacopoeias of various countries and enables the production of a high-quality and stable aqueous polyvinylpyrrolidone-iodine complex solution (povidone-iodine preparation). [Means for solving the problem]

[0008] The present invention has the following aspects. [1] A method for producing a polyvinylpyrrolidone-iodine complex in which polyvinylpyrrolidone and iodine are mixed in the solid phase and then hydrogen iodide is added to cause a reaction. [2] The method according to [1], further comprising the step of performing heat treatment at 100° C. or lower after the addition of hydrogen iodide. [3] The method according to [1] or [2], wherein a mass ratio of the total iodine amount of the iodine and the hydrogen iodide to the polyvinylpyrrolidone is 18 mass% or more based on the dry mass of the polyvinylpyrrolidone. [4] The method according to any one of [1] to [3], wherein a mass ratio of the iodine and the hydrogen iodide used, calculated as iodine, is in the range of 50:50 to 90:10 (iodine:hydrogen iodide). [5] The method according to any one of [1] to [4], further comprising carrying out the reaction in the coexistence of an iodine salt. [6] The method according to [5], wherein a mass ratio of the total iodine amount of the iodine, the hydrogen iodide and the iodine salt to the polyvinylpyrrolidone is more than 18 mass% based on the dry mass of the polyvinylpyrrolidone. [7] The method according to any one of [1] to [6], wherein the water content of the polyvinylpyrrolidone is 4 to 6 mass %. Effect of the Invention

[0009] According to the present invention, it is possible to provide a method for producing a high-quality and stable polyvinylpyrrolidone-iodine complex that satisfies all the standard values ​​of the pharmacopoeias of various countries. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The method for producing the polyvinylpyrrolidone-iodine complex (PVP-I) of the present invention is characterized in that polyvinylpyrrolidone (PVP) and iodine (I2) are mixed in a solid phase, and then hydrogen iodide is added to cause a reaction.

[0011] In the production method of the present invention, PVP obtained by a known method can be used, for example, PVP polymerized in a solvent such as water, isopropanol, or toluene in the presence of a radical polymerization initiator such as a peroxide such as hydrogen peroxide, sodium peroxodisulfate, or dialkyl peroxide, or an azo compound such as azoisobutyronitrile. In addition, PVP that has been hydrogenated with hydrogen or a complex hydride after polymerization, terminal-modified PVP disclosed in JP-T-2003-509347, and PVP copolymerized with a (meth)acrylic acid derivative or the like disclosed in JP-A-51-142094 may also be used in the production method of the present invention.

[0012] The PVP used in the production method of the present invention is preferably one that satisfies the standard values ​​for "povidone" (1-vinyl-2-pyrrolidone polymer = PVP) in the 18th Revised Japanese Pharmacopoeia in terms of the content of each impurity, such as soluble matter, heavy metals, aldehydes, N-vinylpyrrolidone monomer, peroxides, hydrazine, formic acid, pyrrolidone, and ignition residue. Most of these standard values ​​are stipulated based on the harmonized agreement among the three pharmacopoeias, the Japanese Pharmacopoeia, the European Pharmacopoeia, and the United States Pharmacopeia.

[0013] The K value of PVP can be appropriately selected in the range of 10 to 100, preferably 20 to 50, more preferably 25 to 35, and more preferably 25 to 33. If the K value is within the above range, the PVP is easy to handle, and the stability of iodine in PVP-I tends to be maintained. Here, the K value is a constant representing the degree of polymerization proposed by H. Fikentscher, Cellulose-Chemie, 13, 38-64 and 71-74 (1932), and is measured in an aqueous solution.

[0014] From the viewpoints of ease of handling and suppressing the formation of lumps of PVP aggregated by moisture during the present production method, the water content of PVP is preferably in the range of 4 to 6% by mass. The water content of PVP can be adjusted to the above range, if necessary, by drying in a temperature atmosphere in the range of room temperature (30°C) to 90°C, preferably under atmospheric pressure or reduced pressure while stirring.

[0015] Mixing of PVP and iodine in a solid phase is preferably carried out under an inert gas atmosphere such as nitrogen, argon, etc. Mixing is preferably carried out within a range of 10° C. to 35° C. There is no particular limitation on the mixing time as long as the PVP and iodine are sufficiently mixed.

[0016] The mixing means is not particularly limited as long as the PVP and solid iodine can be sufficiently stirred and mixed, and preferably the temperature inside the mixer can be controlled. From the viewpoint of increasing the mixing efficiency of PVP and iodine, which have different specific gravities, and reducing adhesion sites and increasing the extraction yield, a mixing device such as a conical dryer without stirring blades is preferred.

[0017] The mixture is prepared by mixing PVP and iodine in the solid state, and then hydrogen iodide is added to the mixture, which is preferably introduced into the mixing vessel in which the mixture was prepared.

[0018] The amount of hydrogen iodide introduced is preferably 18% by mass or more, more preferably more than 20% by mass, and even more preferably 21% by mass or more, expressed as the total amount of iodine in iodine and hydrogen iodide (total iodine amount) based on the dry PVP mass of the PVP used to prepare the mixture. The total iodine amount is preferably 25% by mass or less based on the dry PVP. Furthermore, hydrogen iodide is preferably added so that the mass ratio of iodine and hydrogen iodide used as the iodine supply source is in the range of iodine:hydrogen iodide=50:50 to 90:10, more preferably 60:40 to 80:20, calculated as iodine. When the total iodine amount and the usage mass ratio are within the above-mentioned ranges, the obtained PVP-I is likely to satisfy the quality standards defined by the pharmacopoeias of various countries, such as the Japanese Pharmacopoeia, and evaluation values ​​such as the distribution coefficient and iodine loss, which will be described later, are likely to reach target levels.

[0019] When PVP and iodine are mixed in advance in a solid phase, preferably at room temperature, an iodine salt may be further added, such as inorganic iodine salts, such as lithium iodide, sodium iodide, potassium iodide, magnesium iodide, barium iodide, etc.; and organic iodine salts, such as ammonium iodide, tetraalkylammonium iodide, etc. Among them, sodium iodide, potassium iodide, and ammonium iodide are preferable. These iodine salts may be used alone or in combination of two or more. When two or more types are used in combination, there is no particular restriction on the ratio of the amounts of iodine salts used.

[0020] When an iodine salt is further added when mixing PVP and iodine, the total amount of iodine in the iodine, hydrogen iodide, and iodine salt (total iodine amount) is preferably 18% by mass or more, more preferably more than 20% by mass, and even more preferably 21% by mass or more, based on the dry PVP. The total iodine amount is preferably 25% by mass or less based on the dry PVP, from the viewpoint that the obtained PVP-I satisfies the quality standards set by the pharmacopoeias of various countries, such as the Japanese Pharmacopoeia. In addition, the iodine salt is preferably added so that the mass ratio of iodine, hydrogen iodide, and iodine salt used as the iodine supply source is in the range of iodine:[hydrogen iodide and iodine salt]=50:50 to 90:10 in terms of iodine, and more preferably in the range of 60:40 to 80:20. In this case, the mass ratio of hydrogen iodide and iodine salt used is in the range of hydrogen iodide:iodine salt=10:90 to 90:10 in terms of iodine, and more preferably in the range of 15:85 to 85:15. When the mass ratios are within the above ranges, the obtained PVP-I is likely to satisfy the quality standards set by the pharmacopoeias of each country, such as the Japanese Pharmacopoeia, and the evaluation values ​​such as the partition coefficient and iodine loss described below are likely to reach the target levels.

[0021] The production method of the present invention can be preferably carried out by first charging PVP, iodine, and optionally an iodine salt into a mixing device and premixing them at room temperature (about 30° C.), then introducing hydrogen iodide as a gas into the device and mixing. It is preferable to add hydrogen iodide to a mixture of PVP and iodine, and then further increase the temperature and mix under heated conditions to perform a heat treatment, from the viewpoint of smoothly and rapidly progressing the reaction and efficiently obtaining stable PVP-I. There is no strict upper limit to the heating temperature, but from the viewpoint of the thermal stability of the PVP itself and the resulting PVP-I, it is usually preferable to set the temperature at 100°C or lower, and it is more preferable to heat the material to a set temperature of 95°C or lower.

[0022] The temperature may be raised to the set temperature in one step or in stages after hydrogen iodide is introduced. There is no particular limit to the rate of temperature rise. There is no strict limit to the time of heat treatment, but from the viewpoint of the thermal stability of the PVP itself and the resulting PVP-I, and of smoothly completing the reaction, it is usually preferably within 10 hours, more preferably within 6 hours, after the temperature is raised to the set temperature. More specifically, after hydrogen iodide is introduced into the mixture containing PVP and iodine, and optionally an iodine salt, the mixture can be mixed and heated while increasing the temperature stepwise, for example, for 2 hours at 50° C., then for 2 hours at 70° C., and then for 5 hours at 90° C. Alternatively, hydrogen iodide may be added to a mixture of PVP and iodine, and the mixture may be mixed and heated at a temperature increased to 90° C. in one step, for example, for heat treatment. Incidentally, hydrogen iodide gas may be introduced into the mixture after the temperature of the prepared mixture is once raised to the set temperature without introducing hydrogen iodide thereinto, and then the mixture is cooled.

[0023] After the heat treatment is completed, the mixing device is cooled to room temperature (approximately 30° C.) by natural cooling or by using a refrigerant, and the PVP-I is taken out as a brown powder.

[0024] The PVP-I obtained by the production method of the present invention has an available iodine content preferably in the range of 10.0% to 12.0%, a ratio of available iodine to iodide ions (available iodine / iodide ions) in the range of 1.8 to 2.4, a distribution coefficient preferably of 200 or more, more preferably in the range of 200 to 250, and an iodine loss preferably of 6.3 or less, more preferably in the range of 4.0 to 6.3. The methods for evaluating the amount of available iodine, available iodine / iodide ion, distribution coefficient, and iodine loss are as described later in the Examples. EXAMPLES

[0025] The present invention will be specifically described below with reference to examples and comparative examples, but the present invention is not limited to these examples, etc. The obtained products were analyzed as follows.

[0026] [Amount of available iodine, amount of iodide ions] The quantity was determined according to the general test method "2. Physical Test Methods 2.50 Titration End Point Detection Method" of the Japanese Pharmacopoeia, 18th Edition, as described in the section "Povidone-iodine."

[0027] [Distribution coefficient] Using the products obtained in each of the Examples and Comparative Examples, samples were prepared so that the available iodine concentration was approximately 1%, and the samples were titrated with a 0.1 mol / L aqueous solution of sodium thiosulfate to determine the amount of available iodine before being subjected to the distribution test. 1 mL of this sample was precisely weighed and dispensed into an Erlenmeyer flask, then 25 mL of heptane was measured with a whole pipette and vigorously shaken at 25°C for 1 hour. After standing, the heptane phase was sampled and placed in a quartz cell, and the absorbance at 520 nm was measured. The amount of iodine in the heptane phase was calculated using the absorbance at 520 nm of heptane alone as a blank value. From this value, the amount of iodine in the aqueous phase was calculated, and the distribution coefficient was calculated from the amounts of iodine in the heptane and aqueous phases.

[0028] [Iodine loss] Using the products obtained in each Example and Comparative Example, a sample was prepared so that the available iodine concentration was about 1%, and 10 mL of the sample was precisely weighed out and the (M L : g) and titrated with a 0.1 mol / L aqueous solution of sodium thiosulfate (titer: L (mL)). 100 mL of the prepared sample was dispensed into a recovery flask with a rotor, plugged, and heated at 80°C for 15 hours. After cooling to 25°C, 10 mL of the sample was precisely weighed (M M:g) and titrated with 0.02 mol / L aqueous sodium thiosulfate solution (titer: M (mL)). Using the above values, the iodine loss (%) was calculated using the following formula. Iodine loss (%) = 100 × (M L / L)×[(L / M L )-(M / M M )]

[0029] <Example 1> 118.5 g of PVP with a water content of 4.0% (equivalent to 113.8 g of dried PVP) and 17.1 g of iodine were placed in a 500 mL eggplant-shaped flask, and the contents were mixed by rotating the eggplant-shaped flask at 30° C. in a rotary evaporator. Next, 7.3 g of hydrogen iodide was introduced into the eggplant-shaped flask over 5 minutes. Here, the total amount of iodine in the iodine and hydrogen iodide (total iodine amount) was 21.4% by mass relative to the mass of dry PVP, and the mass ratio of iodine to hydrogen iodide used in terms of iodine was 70:30. After hydrogen iodide was introduced, the contents were mixed at 30°C for 2 hours, then heated to 50°C for 2 hours, then heated to 70°C for 2 hours, and finally heated to 90°C for 5 hours, all of which were mixed by rotating the eggplant-shaped flask in a rotary evaporator. The contents were cooled to 30°C, and 141.7 g of PVP-I was obtained as a brown powder product (removal yield 99.1%).

[0030] <Example 2> 118.5 g of PVP with a water content of 4.9% (equivalent to 112.7 g of dried PVP), 17.0 g of iodine, and 2.76 g of ammonium iodide were placed in a 500 mL eggplant-shaped flask, and the contents were mixed by rotating the eggplant-shaped flask at 30° C. in a rotary evaporator. Next, 4.85 g of hydrogen iodide was introduced into the eggplant-shaped flask over 5 minutes. The total amount of iodine in the iodine, hydrogen iodide, and ammonium iodide (total iodine amount) was 21.5% by mass relative to the mass of dry PVP, and the mass ratio of iodine, hydrogen iodide, and ammonium iodide used in terms of iodine was 70:20:10. After hydrogen iodide was introduced, the contents were mixed at 30°C for 2 hours, then heated to 50°C for 2 hours, then heated to 70°C for 2 hours, and finally heated to 90°C for 5 hours, all of which were mixed by rotating the eggplant-shaped flask in a rotary evaporator. The contents were cooled to 30°C, and 123.9 g of PVP-I was obtained as a brown powder product (removal yield 87%).

[0031] <Example 3> 118.5g of PVP with a water content of 4.9% (112.7g in terms of dry PVP), 17.0g of iodine, and 5.5g of ammonium iodide were placed in a 500mL eggplant-shaped flask, and the contents were mixed by rotating the eggplant-shaped flask at 30°C in a rotary evaporator. Next, 2.4g of hydrogen iodide was introduced into the eggplant-shaped flask. Here, the total amount of iodine in iodine, hydrogen iodide, and ammonium iodide (total iodine amount) relative to the mass of dry PVP was 21.5% by mass, and the mass ratio of iodine, hydrogen iodide, and ammonium iodide used in terms of iodine was 70:10:20. After hydrogen iodide was added, the contents were heated to 50°C for 4 hours, then to 70°C for 4 hours, and finally to 90°C for 10 hours, all of which were mixed by rotating the eggplant-shaped flask in a rotary evaporator. The contents were cooled to 30°C, and 139.4 g of PVP-I was obtained as a brown powder product (removal yield 97.2%).

[0032] <Example 4> 118.5 g of PVP with a water content of 5.0% (equivalent to 112.6 g of dried PVP) and 15.8 g of iodine were placed in a 500 mL eggplant-shaped flask, and the contents were mixed by rotating the eggplant-shaped flask at 30° C. in a rotary evaporator. Next, 6.8 g of hydrogen iodide was introduced into the eggplant-shaped flask over 5 minutes. Here, the total amount of iodine in the iodine and hydrogen iodide (total iodine amount) was 20.0% by mass relative to the mass of dry PVP, and the mass ratio of iodine to hydrogen iodide used in terms of iodine was 70:30. After hydrogen iodide was introduced, the contents were mixed at 30°C for 2 hours, then heated to 50°C for 2 hours, then heated to 70°C for 2 hours, and finally heated to 90°C for 5 hours, all of which were mixed by rotating the eggplant-shaped flask in a rotary evaporator. The contents were cooled to 30°C, and 123.3 g of PVP-I was obtained as a brown powder product (removal yield 87.5%).

[0033] <Example 5> 118.5 g of PVP with a water content of 5.0% (equivalent to 112.6 g of dried PVP) and 14.6 g of iodine were placed in a 500 mL eggplant-shaped flask, and the contents were mixed by rotating the eggplant-shaped flask at 30° C. in a rotary evaporator. Next, 6.3 g of hydrogen iodide was introduced into the eggplant-shaped flask over 5 minutes. Here, the total amount of iodine in the iodine and hydrogen iodide (total iodine amount) was 18.5% by mass relative to the mass of dry PVP, and the mass ratio of iodine to hydrogen iodide used in terms of iodine was 70:30. After hydrogen iodide was introduced, the contents were mixed at 30°C for 2 hours, then heated to 50°C for 2 hours, then heated to 70°C for 2 hours, and finally heated to 90°C for 5 hours, all of which were mixed by rotating the eggplant-shaped flask in a rotary evaporator. The contents were cooled to 30°C, and 133.76 g of PVP-I was obtained as a brown powder product (removal yield 96.0%).

[0034] <Example 6> 118.5 g of PVP with a water content of 5.0% (equivalent to 112.6 g of dried PVP) and 16.9 g of iodine were placed in a 500 mL eggplant-shaped flask, and the contents were mixed by rotating the eggplant-shaped flask at 30° C. in a rotary evaporator. Next, 7.3 g of hydrogen iodide was introduced into the eggplant-shaped flask over 5 minutes. Here, the total amount of iodine in the iodine and hydrogen iodide (total iodine amount) was 21.4% by mass relative to the mass of dry PVP, and the mass ratio of iodine to hydrogen iodide used in terms of iodine was 70:30. The contents after hydrogen iodide introduction were heated from 30°C to 90°C over 6 hours and 30 minutes, and mixed by rotating the eggplant-shaped flask in a rotary evaporator for 5 hours at 90°C. The contents were cooled to 30°C to obtain 128.7 g of PVP-I as a brown powder product (removal yield 90.2%).

[0035] <Comparative Example 1> 118.5g of PVP with a water content of 4.8% (112.8g in terms of dry PVP) and 24.25g of iodine were placed in a 500mL eggplant-shaped flask, and the contents were mixed by rotating the eggplant-shaped flask at 30°C in a rotary evaporator. Here, the amount of iodine relative to the mass of dry PVP was 21.5% by mass. Next, the temperature was raised to 50°C for 2 hours, further to 70°C for 2 hours, and then to 90°C for 5 hours, all of which were mixed by rotating the eggplant-shaped flask in a rotary evaporator. The contents were cooled to 30°C, and 130.6g of PVP-I was obtained as a brown powder product (removal yield 91.5%).

[0036] <Comparative Example 2> 118.5 g of PVP with a water content of 4.5% (equivalent to 113.2 g of dried PVP) and 23.20 g of iodine were placed in a 500 mL eggplant-shaped flask, and the contents were mixed by rotating the eggplant-shaped flask at 30° C. in a rotary evaporator. Next, 1.13 g of hydrogen iodide was introduced into the eggplant-shaped flask over 5 minutes. Here, the total amount of iodine in the iodine and hydrogen iodide (total iodine amount) relative to the mass of dry PVP was 21.5 mass%, and the mass ratio of iodine to hydrogen iodide used in terms of iodine was 95:5. After hydrogen iodide was introduced, the contents were mixed at 30°C for 2 hours, then heated to 50°C for 2 hours, then heated to 70°C for 2 hours, and finally heated to 90°C for 5 hours, all of which were mixed by rotating the eggplant-shaped flask in a rotary evaporator. The contents were cooled to 30°C, and 134.4 g of PVP-I was obtained as a brown powder product (removal yield 94.1%).

[0037] The amount of available iodine (mass%), the ratio of available iodine / iodide ion, the distribution coefficient, and the iodine loss were determined by the above-mentioned evaluation methods for each of the PVP-I obtained in Examples 1 to 6 and Comparative Examples 1 and 2. The results are summarized in Table 1.

[0038] [Table 1]

[0039] The PVP-I obtained in Examples 1 to 6 satisfies the standards of the Japanese Pharmacopoeia in terms of the amount of available iodine and the value of available iodine / iodide ion, has a distribution coefficient of preferably 200 or more, and an iodine loss of preferably 5.2% or less, and is excellent in quality and storage stability. Furthermore, according to this method, even if PVP and an iodine salt are allowed to coexist prior to the supply of hydrogen iodide as an iodine supply source, PVP-I of excellent quality can be obtained.

[0040] <Example 7> 36.0 kg of PVP with a moisture content of 5.8% (equivalent to 33.9 kg of dry PVP) and 5.0 kg of iodine were placed in a 150 L conical dryer, and the contents were mixed at 30° C. for 17 hours at a rotation speed of 12 rpm. Next, 2.14 kg of hydrogen iodide gas was introduced into the conical dryer over 3 hours. Here, the total amount of iodine in iodine and hydrogen iodide (total iodine amount) relative to the mass of dry PVP was 21.0 mass%, and the mass ratio of iodine to hydrogen iodide used in terms of iodine was 70:30. The contents after the introduction of hydrogen iodide were mixed at 30° C. for 2 hours with the conical dryer rotating at 12 revolutions per minute, then heated to 50° C. and mixed for 2 hours, further heated to 70° C. and mixed for 2 hours, and then heated to 90° C. and mixed for 5 hours. The contents were cooled to 30° C. to obtain 42.2 kg of PVP-I as a brown powder product (removal yield 99.5%). The available iodine content of the obtained PVP-I was 11.3 mass%, the available iodine / iodide ion ratio was 2.0, the distribution coefficient was more than 230, and the iodine loss was less than 5.5%. [Industrial Applicability]

[0041] The polyvinylpyrrolidone-iodine complex obtained by the production method of the present invention is useful as an active ingredient of an aqueous polyvinylpyrrolidone-iodine complex solution (povidone-iodine preparation) for use as a bactericide, disinfectant, etc.

Claims

1. A method for producing a polyvinylpyrrolidone-iodine complex, comprising mixing polyvinylpyrrolidone and iodine in a solid phase state, and then adding hydrogen iodide to cause a reaction, wherein the mass ratio of the iodine and the hydrogen iodide used is in the range of iodine:hydrogen iodide=50:50 to 90:10 in terms of iodine.

2. The method according to claim 1 , further comprising the step of: subjecting the hydrogen iodide to a heat treatment at a temperature of 100° C. or less after the addition of the hydrogen iodide.

3. 2. The method according to claim 1, wherein a mass ratio of a total amount of iodine of the iodine and the hydrogen iodide to the polyvinylpyrrolidone is 18 mass% or more with respect to a dry mass of the polyvinylpyrrolidone.

4. The method according to claim 1 , further comprising carrying out the reaction in the coexistence of an iodine salt.

5. The method according to claim 4, wherein a mass ratio of the total iodine amount of the iodine, the hydrogen iodide and the iodine salt to the polyvinylpyrrolidone is more than 18 mass% with respect to a dry mass of the polyvinylpyrrolidone.

6. The method according to any one of claims 1 to 5, wherein the polyvinylpyrrolidone has a water content of 4 to 6% by mass.

Images