CA1057894A - Manufacture of polyvinylpyrrolidone - Google Patents
Manufacture of polyvinylpyrrolidoneInfo
- Publication number
- CA1057894A CA1057894A CA233,155A CA233155A CA1057894A CA 1057894 A CA1057894 A CA 1057894A CA 233155 A CA233155 A CA 233155A CA 1057894 A CA1057894 A CA 1057894A
- Authority
- CA
- Canada
- Prior art keywords
- polymerization
- polyvinylpyrrolidone
- vinylpyrrolidone
- tert
- parts
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F126/00—Homopolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen
- C08F126/06—Homopolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen by a heterocyclic ring containing nitrogen
- C08F126/10—N-Vinyl-pyrrolidone
Abstract
ABSTRACT
Polyvinylpyrrolidone is manufactured by polymerization of vinylpyrrolidone in an organic solvent in the pre-sence of organic per-compounds wherein an anhydrous organic solvent is used and a heavy metal of atomic number from 23 to 29, in the form of a complex compound or a salt with an organic acid, is added as a co-activator. The polyvinylpyrrolidone manufactured according to the invention is used for pharmaceutical or cosmetic purposes, especially for the manufacture of polyvinylpyrrolidone-iodine.
Polyvinylpyrrolidone is manufactured by polymerization of vinylpyrrolidone in an organic solvent in the pre-sence of organic per-compounds wherein an anhydrous organic solvent is used and a heavy metal of atomic number from 23 to 29, in the form of a complex compound or a salt with an organic acid, is added as a co-activator. The polyvinylpyrrolidone manufactured according to the invention is used for pharmaceutical or cosmetic purposes, especially for the manufacture of polyvinylpyrrolidone-iodine.
Description
s~
The free-radical polymeriza-tion of vinylpyrrolidone in water or alcohols has been disclosed, suitable cata~ysts :
being hydrogen peroxide, alkyl hydroperoxides, dialkyl peroxides and azodiisobutyronitrile. Polymeriza-tion in aqueous solution is industrially important, whilst polymerization in alcohols suffers from severe disadvantages,above all that it proceeds very slowly, even if organic per-compounds are used as activa-tors. In particular, the complete polymerization of the last remnants of vinylpyrrolidone presents considerable difficulties and requires long times. Satisfactory removal of the monomer from the polyrinylpyrrolidone, for example by extraction or chemical reaction, such as hydrolysis, is extremely lnvolved. .
Azodii~obutyronitrile has the addi-tional disadvantage that its decompos.ition product, namely tetramethylsuccinodinltrile, is an undesirable impurity.
In the industrial processes carried out in aqueous solutions, hydrogen peroxide, the preferred catalyst, has the advantage that it also regulates the molecular weight so that the molecular weight of the polyvinylpyrrolidone can be varied by varying the amount of hydrogen perixide.
Since, however, a drop in pH is observed duri.ng polymerization in aqueous solution, using hydrogen peroxide, and monomeric vinylpyrrolidone may undergo hydrolysis at the changed pH, a buffer, e.g. an amine or ammonia, is generally added to maintain the pH at from 6 to 7. Such a buffer has the .
disadvantage that it must subsequently be removed and special measures, e.g. reprecipitation of the polymer, become necessary.
Particularly wherl low molecular weigh-ts, corr-sponding to 1~
values of less than 20, and requiring the addition of relatively large amounts of hydrogen peroxide during the manufac-tnring process, are re~uired, the drop in pH interferes significantly, and thefefore larger amounts of buffer are necessary. Polymers i~)S7899~ ~
of K-value 20 or less also have a great tendency to yellow and possess a low glass transition temperature, whlch makes drying more difficult and gives powders which tend to cake on storage, particularly in a moist atrnosphere. Low molecular weight polyvinyl-pyrrolidone, which is used mainly for pharma-ceutical and cosmetic purposes, and which has to meet particu-larly high quality standards, is therefore relatively difficult to manufacture.
We have now found a process for the manufacture of polyvinylpyrrolidone by polymerization of`vinylpyrrolidone in an organic solvent in the presence of organic per-compounds, wherein anhydrous organic solvents are used and a heavy metal of atomic number from 23 to 29, in the Eorm of a complex compound or of a salt with an organic acid, is added as a coactivator.
The invention provides an industrial process of manufacture of polyvinylpyrrolidone in an organic solvent, which avoids the above disadvantages and gives a polyvinyl-pyrrolidone of superior properties. The poLymerization in the presence of heavy metal takes place extremely rapidly, in - the course of from 3 to 4 hours, very little residual monomer is present and a superior product which in particular is out-standingly suitable for pharmaceutical and cosmetic uses is obtained. Furthermore, the addition of a buffer during the polymerization-is not necessary.
Anhydrous solvents which may be used are open-chain or cyclic acid amides or lactones of lower organic acids, or aliphatic ketones, such as dîmethylformamide, butyrolactone, pyrrolidone and N-methylpyrrolidone, or acetone, methyl ethyl ketone and diethyl ketone.
The preferred solvents are aromatic hydrocarbons, in particular benzene and alkylbenzenes, such as benzene, to:Luene,
The free-radical polymeriza-tion of vinylpyrrolidone in water or alcohols has been disclosed, suitable cata~ysts :
being hydrogen peroxide, alkyl hydroperoxides, dialkyl peroxides and azodiisobutyronitrile. Polymeriza-tion in aqueous solution is industrially important, whilst polymerization in alcohols suffers from severe disadvantages,above all that it proceeds very slowly, even if organic per-compounds are used as activa-tors. In particular, the complete polymerization of the last remnants of vinylpyrrolidone presents considerable difficulties and requires long times. Satisfactory removal of the monomer from the polyrinylpyrrolidone, for example by extraction or chemical reaction, such as hydrolysis, is extremely lnvolved. .
Azodii~obutyronitrile has the addi-tional disadvantage that its decompos.ition product, namely tetramethylsuccinodinltrile, is an undesirable impurity.
In the industrial processes carried out in aqueous solutions, hydrogen peroxide, the preferred catalyst, has the advantage that it also regulates the molecular weight so that the molecular weight of the polyvinylpyrrolidone can be varied by varying the amount of hydrogen perixide.
Since, however, a drop in pH is observed duri.ng polymerization in aqueous solution, using hydrogen peroxide, and monomeric vinylpyrrolidone may undergo hydrolysis at the changed pH, a buffer, e.g. an amine or ammonia, is generally added to maintain the pH at from 6 to 7. Such a buffer has the .
disadvantage that it must subsequently be removed and special measures, e.g. reprecipitation of the polymer, become necessary.
Particularly wherl low molecular weigh-ts, corr-sponding to 1~
values of less than 20, and requiring the addition of relatively large amounts of hydrogen peroxide during the manufac-tnring process, are re~uired, the drop in pH interferes significantly, and thefefore larger amounts of buffer are necessary. Polymers i~)S7899~ ~
of K-value 20 or less also have a great tendency to yellow and possess a low glass transition temperature, whlch makes drying more difficult and gives powders which tend to cake on storage, particularly in a moist atrnosphere. Low molecular weight polyvinyl-pyrrolidone, which is used mainly for pharma-ceutical and cosmetic purposes, and which has to meet particu-larly high quality standards, is therefore relatively difficult to manufacture.
We have now found a process for the manufacture of polyvinylpyrrolidone by polymerization of`vinylpyrrolidone in an organic solvent in the presence of organic per-compounds, wherein anhydrous organic solvents are used and a heavy metal of atomic number from 23 to 29, in the Eorm of a complex compound or of a salt with an organic acid, is added as a coactivator.
The invention provides an industrial process of manufacture of polyvinylpyrrolidone in an organic solvent, which avoids the above disadvantages and gives a polyvinyl-pyrrolidone of superior properties. The poLymerization in the presence of heavy metal takes place extremely rapidly, in - the course of from 3 to 4 hours, very little residual monomer is present and a superior product which in particular is out-standingly suitable for pharmaceutical and cosmetic uses is obtained. Furthermore, the addition of a buffer during the polymerization-is not necessary.
Anhydrous solvents which may be used are open-chain or cyclic acid amides or lactones of lower organic acids, or aliphatic ketones, such as dîmethylformamide, butyrolactone, pyrrolidone and N-methylpyrrolidone, or acetone, methyl ethyl ketone and diethyl ketone.
The preferred solvents are aromatic hydrocarbons, in particular benzene and alkylbenzenes, such as benzene, to:Luene,
- 2 -lV~
ethylbenzene and cumene, and lower aliphatic monohydric alcohols, in particular of 1 to 4 carbon a-toms, such as methanol, ethanol, propanol, isopropanol, n-butanol, i-butanol and 2 butanol. Amongst these, isopropanol should be singled out particularly. When used to manufacture polyvinylpyrrolidone of molecular weigh-t less than 40,000, it exerts an advantageous regulating action.
The heavy metals of atomic numbers from 23 to 29 are vanadium, chromium, manganese, iron, cobalt, nickel and copper These compounds are exceptionally effective and are used in very small amounts, suitably in amounts of frorn 0.01 to 10 ppm, preferably from 0.1 to 5 ppm, based on the weight of the vinyl- ;
pyrrolidone. Amongst the heavy metals mentioned, copper, manganese and cobalt are preferred, and in turn copper is particularly preferred.
Organic acids which may be used to form salts (of the said metals) are aliphatic carboxylic acids of 2 to 1 carbon atoms, e.g. acetic acid, propionic acid, butyric acid, ethyl-hexanoic acid and stearic acid, and aroma-tic acids, e.g.
benzoic acid and phenylacetic acid.
Naphthenic acids, such as are used, e.g., for the manufacture of driers, may also be used.
Furthermore, the heavy metals may be employed in the form of chelate complexes or in the form of other complexes.
Suitable complexing agents are e.g. ~-diketones, such as acetylacetone, hydroxyketones, such as hydroxy-acetone, hydroxy-carboxylic acids, such as lactic acid, citric acid and salicylic acid, aminoacids, such as glycine, ethylenediaminetetraacetic acid and anthranilic acid, aldoximines, such as ethylene-bis-salicylaldoxime, and aminoalcohols, such as triethanolamine.
Specific examples of heavy metal salts and complex compounds are copper acetate, copper acetylacetonate, copper . .
~a)57~
stearate, cobalt ethylhexanoate, cobalt naphthenate, nickel glycinate, manganese-II acetate, manganese-II salicylate and chromium-III benzoate.
Suitable organic per-compounds which initiate the free-radical polymerization are those conventionally employed for polymerization purposes. Specific examples are alkyl hydroperoxides, e.g. -tert.-butyl hydroperoxide, cumene hydro-peroxide, dialkyl peroxides, e.g. di-tert.-butyl peroxide, dicumyl peroxide, diacyl peroxides, e.g. dibenzoyl peroxide, and peresters, such as tert.-butyl perpivalate, tert.-butyl ~-peroctoate and tert.-butyl perbenzoate, perketals, e.g. 2,2-bis-(tert.-butylperoxy)-butane, aldehyde-peroxides and keto-peroxides, such as methyl ethyl ketone-peroxide.
Frequently, t-butyl-perbenzoate, tert.-bu-tyl hydro-peroxide and di-tert.-butyl peroxide offer advantages, since their decomposition products are water-soluble. To manufacture a particularly pure polyvinylpyrrolidone, di-tert.-butyl peroxide and tert.-butyl hydroperoxide are of particular interest, since their decomposition produc-ts can easily be removed, e.g. by steam distillation.
The amount of the organic per-compounds can vary within wide limits and depends on the molecular weight required.
In general, the amount is from o.i to 8%, preferably from 0.5 to 5%, based on the weight of vinylpyrrolidone.
The actual polymerization is carried out by conven-tional methods. In general, all components of the batch are mixed from the start. In many cases it may, however, be appropriate to run in one or more components during the polymerization. Suitably, the air or oxygen contained in the solutions is removed, before starting the polymerization, by subjecting the solution to reduced pressure or flush:Lng it with nitrogen. Suitable temperatures are from about 50 to .. . .
:~0~71~99~ ~ ~
150C. In general, the reaction is carried out at the boil under atmospheric pressure. The boiling point and thus the polymerization temperature can be varied within wide limits ~ ;
by use of superatmospheric pressure or reduced pressure and by choice of the solvent. Essentially, the molecular weight and K-value are adjusted to the required figures by choice of the solvent, concentration of the batch, nature and amount of the activator and coactivator, and choice of the polymeriza-tion temperature. Solvents with a tertiary hydrogen atom in general give lower K-values than solvents which only contain . .
secondary or primary hydrogen atoms. Examples are isopropanol compared with ethanol, and cumene compared with benzene. An increase in the monomer concentration also increases the K-value, as may be seen from Table ~.
As a rule, the monomer concentration is from 10 to 75, preferably from 15 to 70 % by weight, The molecular welgh-t of the polymer may be lowered by slowly adding the vinyl-pyrrolidone during the polymerization. Increasing the amount of activator and raising the polymerization temperature both lower the K-value. Polymers with average molecular weights of from 7,000 to 800,000 and K-values of from about 10 to 90 may be manufac-tured by the process of the invention. The process is particularly suitable Eor the manufac-ture of polymers with IC-values of from 10 to 50. The IC-values are measured by the method of H. Fikentscher, Cellulosechemie 13 (1932), 58 - 64 and 71 - 74, in 5% strength aqueous solutions ~
for K-values of less than 20 and in 1% strength aqueous `
solution for K-values above 20, at 20C. "K" corresponds to the parameter "k . 103" defined by Fikentscher.
I'he course of the polymerization can be followed -easily by con-tinual sampling and determination of the residual vinylpyrrolidone. ~len the latter has fallen signir:icantly -` ` 1057~9~
:
below 1%, the polymerization can be discontinued.
The solutions obtained are worked up in the conven-tional way, e.g. by direct drying in accordance with conven-tional methods such as spray drying, drum drying or freeze drying.
In some cases it is desirable to dilute the batch with water, if appropriate distil off all or part o~ the organic solven-t, and then to dry the product. It is frequently advantageous to interpolate a steam distillation to remove volatiles, e.g. originating from the vinylpyrrolidone or the activator, from the solution. This makes it possible to obtain completely clear aqueous solutions, especially when using, e.g., tert.-butyl hydroperoxide, di-tert.-butyl peroxide, tert.-butyl perbenzoate or ketone-peroxides.
The polyvinylpyrrolidone manukactured acco~dlng to the invention may be used for pharmaceutical or cosmetic purposes e.g. as a carrier, diluent, dispersing agent or solubilizing agent, or for injections. It has a number of ;
advantages over a polyvinylpyrrolidone manufactured according to the art, e.g. according to German Patent 922,378. The ~ .
product is easy to dry. It is possible to manufacture even low molecular weight polymers, of I~-value 15, which are `
completely colorless and can be dried in a spray drier without sintering. Drying is particularly important in the case of ~
polyvinylpyrrolidones used for pharmaceutical purposes, since ~ ~-the dried product does not act as a nutrient medium for micro-organisms and hence no pyrogen can form on storage. Further-more, the aqueous solutions have better heat stability and discolor very little on sterilization.
The PV~ manufactured according to the invention is outstandingly suitable for the manufacture o~ polyvinylpyrro-lidone-iodine (PVP-I). Compared to corr~ercially available ~ _ 1(~57~
polyvinylpyrrolidone, a substantially smaller proportion of iodine is lost as inactive hydrogen iodide on reaction with iodine and an outstandingly stable P~P-I, and substantially - more stable formulations thereof, may be manufactured.
(a) 700 parts of vinylpyrrolidone and 300 parts of isopropanol are mixed in a stirred flask. ~fter adding 7 parts of tert.-butyl hydroperoxide, the mixture is heated to the boil (about 98C). The course of the polymerization is followed by determining the residual vinylpyrrolidone content by the method of Siggia and Edsberg, Anal. Chernistry 20 (1948), 762.
(b) Using an identical batch to l(a), 0,0007 part of manganese acetate (1 ppm, based on the weight oE vinylpyrroli-done) is added, in the ~orm of a very dilute solution in 20 parts o~ anhydrous isopropanol, in the course of 20 minutes, starting 10 minu-tes after reaching the boiling point of 98C.
The -table which follows shows the residual vinylpyrro-lidone content during the polymerization.
TABLE 1 ~`
Residual content of vinylpyrrolidone based on the weight of vinylpyrrolidone employed Time (hoursExperiment a Experiment b 1 80% 18%
2 62% 3%
ethylbenzene and cumene, and lower aliphatic monohydric alcohols, in particular of 1 to 4 carbon a-toms, such as methanol, ethanol, propanol, isopropanol, n-butanol, i-butanol and 2 butanol. Amongst these, isopropanol should be singled out particularly. When used to manufacture polyvinylpyrrolidone of molecular weigh-t less than 40,000, it exerts an advantageous regulating action.
The heavy metals of atomic numbers from 23 to 29 are vanadium, chromium, manganese, iron, cobalt, nickel and copper These compounds are exceptionally effective and are used in very small amounts, suitably in amounts of frorn 0.01 to 10 ppm, preferably from 0.1 to 5 ppm, based on the weight of the vinyl- ;
pyrrolidone. Amongst the heavy metals mentioned, copper, manganese and cobalt are preferred, and in turn copper is particularly preferred.
Organic acids which may be used to form salts (of the said metals) are aliphatic carboxylic acids of 2 to 1 carbon atoms, e.g. acetic acid, propionic acid, butyric acid, ethyl-hexanoic acid and stearic acid, and aroma-tic acids, e.g.
benzoic acid and phenylacetic acid.
Naphthenic acids, such as are used, e.g., for the manufacture of driers, may also be used.
Furthermore, the heavy metals may be employed in the form of chelate complexes or in the form of other complexes.
Suitable complexing agents are e.g. ~-diketones, such as acetylacetone, hydroxyketones, such as hydroxy-acetone, hydroxy-carboxylic acids, such as lactic acid, citric acid and salicylic acid, aminoacids, such as glycine, ethylenediaminetetraacetic acid and anthranilic acid, aldoximines, such as ethylene-bis-salicylaldoxime, and aminoalcohols, such as triethanolamine.
Specific examples of heavy metal salts and complex compounds are copper acetate, copper acetylacetonate, copper . .
~a)57~
stearate, cobalt ethylhexanoate, cobalt naphthenate, nickel glycinate, manganese-II acetate, manganese-II salicylate and chromium-III benzoate.
Suitable organic per-compounds which initiate the free-radical polymerization are those conventionally employed for polymerization purposes. Specific examples are alkyl hydroperoxides, e.g. -tert.-butyl hydroperoxide, cumene hydro-peroxide, dialkyl peroxides, e.g. di-tert.-butyl peroxide, dicumyl peroxide, diacyl peroxides, e.g. dibenzoyl peroxide, and peresters, such as tert.-butyl perpivalate, tert.-butyl ~-peroctoate and tert.-butyl perbenzoate, perketals, e.g. 2,2-bis-(tert.-butylperoxy)-butane, aldehyde-peroxides and keto-peroxides, such as methyl ethyl ketone-peroxide.
Frequently, t-butyl-perbenzoate, tert.-bu-tyl hydro-peroxide and di-tert.-butyl peroxide offer advantages, since their decomposition products are water-soluble. To manufacture a particularly pure polyvinylpyrrolidone, di-tert.-butyl peroxide and tert.-butyl hydroperoxide are of particular interest, since their decomposition produc-ts can easily be removed, e.g. by steam distillation.
The amount of the organic per-compounds can vary within wide limits and depends on the molecular weight required.
In general, the amount is from o.i to 8%, preferably from 0.5 to 5%, based on the weight of vinylpyrrolidone.
The actual polymerization is carried out by conven-tional methods. In general, all components of the batch are mixed from the start. In many cases it may, however, be appropriate to run in one or more components during the polymerization. Suitably, the air or oxygen contained in the solutions is removed, before starting the polymerization, by subjecting the solution to reduced pressure or flush:Lng it with nitrogen. Suitable temperatures are from about 50 to .. . .
:~0~71~99~ ~ ~
150C. In general, the reaction is carried out at the boil under atmospheric pressure. The boiling point and thus the polymerization temperature can be varied within wide limits ~ ;
by use of superatmospheric pressure or reduced pressure and by choice of the solvent. Essentially, the molecular weight and K-value are adjusted to the required figures by choice of the solvent, concentration of the batch, nature and amount of the activator and coactivator, and choice of the polymeriza-tion temperature. Solvents with a tertiary hydrogen atom in general give lower K-values than solvents which only contain . .
secondary or primary hydrogen atoms. Examples are isopropanol compared with ethanol, and cumene compared with benzene. An increase in the monomer concentration also increases the K-value, as may be seen from Table ~.
As a rule, the monomer concentration is from 10 to 75, preferably from 15 to 70 % by weight, The molecular welgh-t of the polymer may be lowered by slowly adding the vinyl-pyrrolidone during the polymerization. Increasing the amount of activator and raising the polymerization temperature both lower the K-value. Polymers with average molecular weights of from 7,000 to 800,000 and K-values of from about 10 to 90 may be manufac-tured by the process of the invention. The process is particularly suitable Eor the manufac-ture of polymers with IC-values of from 10 to 50. The IC-values are measured by the method of H. Fikentscher, Cellulosechemie 13 (1932), 58 - 64 and 71 - 74, in 5% strength aqueous solutions ~
for K-values of less than 20 and in 1% strength aqueous `
solution for K-values above 20, at 20C. "K" corresponds to the parameter "k . 103" defined by Fikentscher.
I'he course of the polymerization can be followed -easily by con-tinual sampling and determination of the residual vinylpyrrolidone. ~len the latter has fallen signir:icantly -` ` 1057~9~
:
below 1%, the polymerization can be discontinued.
The solutions obtained are worked up in the conven-tional way, e.g. by direct drying in accordance with conven-tional methods such as spray drying, drum drying or freeze drying.
In some cases it is desirable to dilute the batch with water, if appropriate distil off all or part o~ the organic solven-t, and then to dry the product. It is frequently advantageous to interpolate a steam distillation to remove volatiles, e.g. originating from the vinylpyrrolidone or the activator, from the solution. This makes it possible to obtain completely clear aqueous solutions, especially when using, e.g., tert.-butyl hydroperoxide, di-tert.-butyl peroxide, tert.-butyl perbenzoate or ketone-peroxides.
The polyvinylpyrrolidone manukactured acco~dlng to the invention may be used for pharmaceutical or cosmetic purposes e.g. as a carrier, diluent, dispersing agent or solubilizing agent, or for injections. It has a number of ;
advantages over a polyvinylpyrrolidone manufactured according to the art, e.g. according to German Patent 922,378. The ~ .
product is easy to dry. It is possible to manufacture even low molecular weight polymers, of I~-value 15, which are `
completely colorless and can be dried in a spray drier without sintering. Drying is particularly important in the case of ~
polyvinylpyrrolidones used for pharmaceutical purposes, since ~ ~-the dried product does not act as a nutrient medium for micro-organisms and hence no pyrogen can form on storage. Further-more, the aqueous solutions have better heat stability and discolor very little on sterilization.
The PV~ manufactured according to the invention is outstandingly suitable for the manufacture o~ polyvinylpyrro-lidone-iodine (PVP-I). Compared to corr~ercially available ~ _ 1(~57~
polyvinylpyrrolidone, a substantially smaller proportion of iodine is lost as inactive hydrogen iodide on reaction with iodine and an outstandingly stable P~P-I, and substantially - more stable formulations thereof, may be manufactured.
(a) 700 parts of vinylpyrrolidone and 300 parts of isopropanol are mixed in a stirred flask. ~fter adding 7 parts of tert.-butyl hydroperoxide, the mixture is heated to the boil (about 98C). The course of the polymerization is followed by determining the residual vinylpyrrolidone content by the method of Siggia and Edsberg, Anal. Chernistry 20 (1948), 762.
(b) Using an identical batch to l(a), 0,0007 part of manganese acetate (1 ppm, based on the weight oE vinylpyrroli-done) is added, in the ~orm of a very dilute solution in 20 parts o~ anhydrous isopropanol, in the course of 20 minutes, starting 10 minu-tes after reaching the boiling point of 98C.
The -table which follows shows the residual vinylpyrro-lidone content during the polymerization.
TABLE 1 ~`
Residual content of vinylpyrrolidone based on the weight of vinylpyrrolidone employed Time (hoursExperiment a Experiment b 1 80% 18%
2 62% 3%
3 48% 1%
4 37% 0.4%
150 parts of vinylpyrrolidone and 850 parts of isopropanol are mixed in a glass apparatus equipped with a reflux condenser and 5 tirrer. The tert.-butyl hydroperoxide is added in the amounts shown in the table below, and the : , ., ~ -mixture is heated to the boil (about 82C). After reaching the boiling point, 1 ppm (based on vinylpyrrolidone) of copper acetate is added, in the way indicated in Example 1, and heating under reflux is continued. After from 6 to 8 hours, the polymerization is complete and the residual monomer content-is less than 0.5%.
~nount of -tert.-butyl hydroperoxide Experiment (% by weight based on K-value vinylpyrrolidone) : ..
The reaction mixture is concentrated to 70% by distilling off a part of the isopropanol and is then diluted to a 30% strength solution with wa-ter. These solutions are spray-dried in a spray drier at an air input temperature of 1~0C and an air output temperature of 80C, a whi-te powder containing about 5% of water being produced.
20% strength solutions in a normal acetate buffer solution are prepared from the polyvinylpyrrolidones from -Experiments 3 and 4, and are sterilized. ~efore and after the sterilization, the iodine color number is determined in accordance with DIN 53,403, in comparison with a polymer of the same K value which was manufactured according to German Patent 922,378 and is a commercial product.
~ .
~L~57894~
Freshly prepared 20% strength PVP solutions in ac~tat:~ bufEer of p~l 5.3 Iodine color Iodine color number~ number accord-according to ing -to ~IN
PVP grade DI~ 53,~03, 53,403, after before sterilization sterilization for 1/2 hour at 120C
PVP K 17, German Patent 922,378 2 9 - 10 PVP K 17, process according to the pre~sent invention 1 - 2 2 - 3 PVP K 15, German Patent 922,378 2 - 3 10 - 12 PVP K 14, process according to the Present invention 2 2 - 3 , The experiments show that the solu-tions of the PVP
manufactured according to the invention are substantially less colored even before sterilization, bu-t particularly after s-terilization, than comparable solutions of polymers according , to German Patent 922,378.
A PVP of K-value 15, manufactured according to German Patent 922,378, can only be spray-dried if the-drying temperature, i.e. the air input temperature and air output temperature, is ~:
lowered by about 20C compared to that used when drying the PVP manufactured according to the invention. On storing the PVP manufactured according to the invention (of 5.2% water content) together wi.th the above comparative product, of 3.8%
water content, at 80C, product 4 remains unchanged whilst the comparative product sinters substantially, in spite of _ 9 _ -:
: . . , . . :
~OS78~ ~
its low water content.
S00 parts of vinylpyrrolidone are mixed with isopro-panol, in the amounts shown in the table below, in a glass flask equipped with a stirrer and reflux condenser, and after adding 5 parts of tert.-butyl hydroperoxide the mixture is heated to the boil. After reaching the boiling point, 0.5 ppm of copper acetylacetonate is added as in Example 1 and the batch is heated until the residual vinylpyrrolidone content is < 0.5%. The solid PVP is then isolated by spray-drying.
Experiment Amount of Popymerization I<-value isopropanol temperature C
.
1 1,500 parts 85 to 82 23.6 2 500 par-ts 92 to 86 27.S
3 214 parts 96 to 88 29.5 500 parts of vinylpyrrolidone are mixed with 240 parts of isopropanol in a glass flask equipped with a stirrer and after adding the activator in accordance with Table 5, the mixture is heated at -the boil (96 to 88C, the boiling tempera-ture initially being 96C and then gradually decreasing to 88C~. 1 ppm of copper acetate is added, as in Example 1, in the course of 5 hours. The reaction is complete after from
150 parts of vinylpyrrolidone and 850 parts of isopropanol are mixed in a glass apparatus equipped with a reflux condenser and 5 tirrer. The tert.-butyl hydroperoxide is added in the amounts shown in the table below, and the : , ., ~ -mixture is heated to the boil (about 82C). After reaching the boiling point, 1 ppm (based on vinylpyrrolidone) of copper acetate is added, in the way indicated in Example 1, and heating under reflux is continued. After from 6 to 8 hours, the polymerization is complete and the residual monomer content-is less than 0.5%.
~nount of -tert.-butyl hydroperoxide Experiment (% by weight based on K-value vinylpyrrolidone) : ..
The reaction mixture is concentrated to 70% by distilling off a part of the isopropanol and is then diluted to a 30% strength solution with wa-ter. These solutions are spray-dried in a spray drier at an air input temperature of 1~0C and an air output temperature of 80C, a whi-te powder containing about 5% of water being produced.
20% strength solutions in a normal acetate buffer solution are prepared from the polyvinylpyrrolidones from -Experiments 3 and 4, and are sterilized. ~efore and after the sterilization, the iodine color number is determined in accordance with DIN 53,403, in comparison with a polymer of the same K value which was manufactured according to German Patent 922,378 and is a commercial product.
~ .
~L~57894~
Freshly prepared 20% strength PVP solutions in ac~tat:~ bufEer of p~l 5.3 Iodine color Iodine color number~ number accord-according to ing -to ~IN
PVP grade DI~ 53,~03, 53,403, after before sterilization sterilization for 1/2 hour at 120C
PVP K 17, German Patent 922,378 2 9 - 10 PVP K 17, process according to the pre~sent invention 1 - 2 2 - 3 PVP K 15, German Patent 922,378 2 - 3 10 - 12 PVP K 14, process according to the Present invention 2 2 - 3 , The experiments show that the solu-tions of the PVP
manufactured according to the invention are substantially less colored even before sterilization, bu-t particularly after s-terilization, than comparable solutions of polymers according , to German Patent 922,378.
A PVP of K-value 15, manufactured according to German Patent 922,378, can only be spray-dried if the-drying temperature, i.e. the air input temperature and air output temperature, is ~:
lowered by about 20C compared to that used when drying the PVP manufactured according to the invention. On storing the PVP manufactured according to the invention (of 5.2% water content) together wi.th the above comparative product, of 3.8%
water content, at 80C, product 4 remains unchanged whilst the comparative product sinters substantially, in spite of _ 9 _ -:
: . . , . . :
~OS78~ ~
its low water content.
S00 parts of vinylpyrrolidone are mixed with isopro-panol, in the amounts shown in the table below, in a glass flask equipped with a stirrer and reflux condenser, and after adding 5 parts of tert.-butyl hydroperoxide the mixture is heated to the boil. After reaching the boiling point, 0.5 ppm of copper acetylacetonate is added as in Example 1 and the batch is heated until the residual vinylpyrrolidone content is < 0.5%. The solid PVP is then isolated by spray-drying.
Experiment Amount of Popymerization I<-value isopropanol temperature C
.
1 1,500 parts 85 to 82 23.6 2 500 par-ts 92 to 86 27.S
3 214 parts 96 to 88 29.5 500 parts of vinylpyrrolidone are mixed with 240 parts of isopropanol in a glass flask equipped with a stirrer and after adding the activator in accordance with Table 5, the mixture is heated at -the boil (96 to 88C, the boiling tempera-ture initially being 96C and then gradually decreasing to 88C~. 1 ppm of copper acetate is added, as in Example 1, in the course of 5 hours. The reaction is complete after from
5 to 7 hours.
TAsLE 5 Experiment Amount (% by Activator K-value weight based type on vinyl-pyrrolidone) ..
1 1.7 Cumene hydroperoxide 27.5 ~-2 3.0 Dicumyl peroxide 48 -- 1 0 - ' ~vs~9~
3 1.6 Di-tert.-butyl 49 peroxide 4 1.4 Methyl ethyl 38 ketone peroxide 1.8 tert.-butyl 30.5 perbenzoate 500 parts of vinylpyrrolidone and 500 parts of solvent according to Table 6 are heated to the boil in a stirred flask, after having added the activator. 0.5 ppm of cobalt ethylhexanoate is added as in the way indicated in Example 1. The polymerization is complete after from 3 to 5 hours.
Experi- Solvent Amount Activator Polymerizatiorl ment (parts) Type tempera- K-vallle _ _ ture 1 Toluene 10 Di-tert.-butyl about 125 42.2 peroxlde 2 Ethanol 5 tert.-butyl about 82 30.0 hydroperoxide 3 n-Butanol 2.5 Di-tert.-bu-tyl about 127 ~9.1 peroxide 4 i-Butanol 10 Di-tert.-butyl about 118 50.6 peroxide :
Polymers with K-values of 15, 17 and 30 are manu-factured in accordance with German Patent 922,378. The polymer solutions are spray-dried. The acid number of the powders obtained is determined and compared with PVP according to the invention, which has -the same K-values and ha.s also been spray-dried.
~)57~4 ` ~
Product K-value Acid-number . :
according to German Patent 922,378 15 12 according to the invention 1.5 0.9 according to German Patent 922,378 17 6 according to the invention 17 0.8 according to German Patent 922,378 30 3 ~ ' according to the invention 29.5 0.2 ' Us.e of the polyvinylpyrrolidone for the manufacture ,~
of PVP-I:
(a) ~00 parts of a polyvinylpyrrolidone manufactured "
according to the invention, having a K-value of 30.5 and a water content of 2.0%, are mixed with 74.6 parts of finely ground iodine in a tumbler mixer for 5 hours at room tempera~
ture. The mixture is then kept at 95C for 10 hours, after which time the content of available iodine, followed by titration, ,no longer changes.
(b) The water content of the polyvinylpyrrolidone ::
used in a) is adjusted to 5~0% by moistening. 400 parts of this polyvinylpyrrolidone are mixed with 72.3 pa,rts of ground iodine for 5 hours at room -temperature and the mixture is then heated for 10 hours at 90C. ..
tc) The water content of the polyvinylpyrrolidone used in (a) is adjusted to 9.1% by moistening. 400 parts of this polyvinylpyrrolidone are mixed with 70 parts of ground iodine for 5 hours at room temperature and the mixture is ;~
then heated for 10 hours at 70C.
The test results on the products are shown in the table below.
105'^~
a b c Solids content (after 3 hours at 105C) 98~8% 95.7% 92.2%
Available iodine content 11.0% 11.4% 11.7%
Loss of available iodine on storing the aqueous solution, containing 1% of available iodine, for 14 days at 52C 5.0% 4.1% 4.1%
COM2ARATIVE FXAMPL~
For comparison, the experiments are carried out with a polyvinylpyrrolidone of K-value 30 which has been manufactured :
according to German Paten-t 922,378 by polymerization in aqueous solution with hydrogen peroxide as the activator, and which corresponds to commercially available products. The water content of the polyvinylpyrrolidone obtained is adjustecl to various values by drying or molstening.
(a) 400 parts of this polyvinylpyrrolidone, containing 1.8% of water, are m:ixed with 74.8 parts of ground iodine for 5 hours at room temperature and the mixture is then heated for 10 hours at 95C. ~; :
(b) 400 parts of polyvinylpyrrolidone containing 5.0%
of water are mixed with 72.3 parts of ground iodine for 5 hours at room temperature and the mixture is then heated for 10 hours at 90~C ~in accordance with U.S. Pa-~ent 2,900,305).
(c) 400 parts of polyvinylpyrrolidone containing 9.5% o:E water are mixed with 78.9 parts of ground iodine for 5 hours at room temperature and the mixture is then heated for 10 hours at 70C (in accordance with U.S. Patent 2,900,305).
The test results are shown in the table which follows.
a b c . Solids content (after 3 hours at 105C) 99.0 % 95.8 % 92.0 %
Available iodine content 10.3 %10.5 %10.5 %
Loss of available iodine on storing -the aqueous solution, containing 1% of available iodine, for 14 days at 52C26 % 17 % 12 %
As may be seen from Example 7 and the comparative 11~5'~ 4 example, the iodine content of the PVP-I i9 about 1% higher than when using a polyvinylpyrrolidone which has been polymerized in aqueous solution, i.e. the loss of iodine is about 20% less.
The loss of available iodine in the aqueous solution during the storage test is substantially independent of the water content of the polyvinylpyrrolidone used and is substantially less than the loss in the comparative experiment. These results show the superiority of the polyvinylpyrrolidone, manufactured according to the invention, for the manufacture ~ ~-of PVP-I.
The formulations intended for the ultimate user can be manufactured from the PVP-I, ob-tained according to the invention, by conventional methods of the art, employing -the conventional pharmaceutical auxiliaries. Preferred forms of formulations are aqueous solutions which contain, as auxiliaries, e.g,, surfactants, alcohol, glycerol and buffer substances such as trisodium phosphate or sodium bicarbonate. These formulations can also be prepared with added hydrogen peroxide.
Other suitable formulations are soap solutions, shampoos, powders, gels and sprays.
' "' ' '"'; , ,
TAsLE 5 Experiment Amount (% by Activator K-value weight based type on vinyl-pyrrolidone) ..
1 1.7 Cumene hydroperoxide 27.5 ~-2 3.0 Dicumyl peroxide 48 -- 1 0 - ' ~vs~9~
3 1.6 Di-tert.-butyl 49 peroxide 4 1.4 Methyl ethyl 38 ketone peroxide 1.8 tert.-butyl 30.5 perbenzoate 500 parts of vinylpyrrolidone and 500 parts of solvent according to Table 6 are heated to the boil in a stirred flask, after having added the activator. 0.5 ppm of cobalt ethylhexanoate is added as in the way indicated in Example 1. The polymerization is complete after from 3 to 5 hours.
Experi- Solvent Amount Activator Polymerizatiorl ment (parts) Type tempera- K-vallle _ _ ture 1 Toluene 10 Di-tert.-butyl about 125 42.2 peroxlde 2 Ethanol 5 tert.-butyl about 82 30.0 hydroperoxide 3 n-Butanol 2.5 Di-tert.-bu-tyl about 127 ~9.1 peroxide 4 i-Butanol 10 Di-tert.-butyl about 118 50.6 peroxide :
Polymers with K-values of 15, 17 and 30 are manu-factured in accordance with German Patent 922,378. The polymer solutions are spray-dried. The acid number of the powders obtained is determined and compared with PVP according to the invention, which has -the same K-values and ha.s also been spray-dried.
~)57~4 ` ~
Product K-value Acid-number . :
according to German Patent 922,378 15 12 according to the invention 1.5 0.9 according to German Patent 922,378 17 6 according to the invention 17 0.8 according to German Patent 922,378 30 3 ~ ' according to the invention 29.5 0.2 ' Us.e of the polyvinylpyrrolidone for the manufacture ,~
of PVP-I:
(a) ~00 parts of a polyvinylpyrrolidone manufactured "
according to the invention, having a K-value of 30.5 and a water content of 2.0%, are mixed with 74.6 parts of finely ground iodine in a tumbler mixer for 5 hours at room tempera~
ture. The mixture is then kept at 95C for 10 hours, after which time the content of available iodine, followed by titration, ,no longer changes.
(b) The water content of the polyvinylpyrrolidone ::
used in a) is adjusted to 5~0% by moistening. 400 parts of this polyvinylpyrrolidone are mixed with 72.3 pa,rts of ground iodine for 5 hours at room -temperature and the mixture is then heated for 10 hours at 90C. ..
tc) The water content of the polyvinylpyrrolidone used in (a) is adjusted to 9.1% by moistening. 400 parts of this polyvinylpyrrolidone are mixed with 70 parts of ground iodine for 5 hours at room temperature and the mixture is ;~
then heated for 10 hours at 70C.
The test results on the products are shown in the table below.
105'^~
a b c Solids content (after 3 hours at 105C) 98~8% 95.7% 92.2%
Available iodine content 11.0% 11.4% 11.7%
Loss of available iodine on storing the aqueous solution, containing 1% of available iodine, for 14 days at 52C 5.0% 4.1% 4.1%
COM2ARATIVE FXAMPL~
For comparison, the experiments are carried out with a polyvinylpyrrolidone of K-value 30 which has been manufactured :
according to German Paten-t 922,378 by polymerization in aqueous solution with hydrogen peroxide as the activator, and which corresponds to commercially available products. The water content of the polyvinylpyrrolidone obtained is adjustecl to various values by drying or molstening.
(a) 400 parts of this polyvinylpyrrolidone, containing 1.8% of water, are m:ixed with 74.8 parts of ground iodine for 5 hours at room temperature and the mixture is then heated for 10 hours at 95C. ~; :
(b) 400 parts of polyvinylpyrrolidone containing 5.0%
of water are mixed with 72.3 parts of ground iodine for 5 hours at room temperature and the mixture is then heated for 10 hours at 90~C ~in accordance with U.S. Pa-~ent 2,900,305).
(c) 400 parts of polyvinylpyrrolidone containing 9.5% o:E water are mixed with 78.9 parts of ground iodine for 5 hours at room temperature and the mixture is then heated for 10 hours at 70C (in accordance with U.S. Patent 2,900,305).
The test results are shown in the table which follows.
a b c . Solids content (after 3 hours at 105C) 99.0 % 95.8 % 92.0 %
Available iodine content 10.3 %10.5 %10.5 %
Loss of available iodine on storing -the aqueous solution, containing 1% of available iodine, for 14 days at 52C26 % 17 % 12 %
As may be seen from Example 7 and the comparative 11~5'~ 4 example, the iodine content of the PVP-I i9 about 1% higher than when using a polyvinylpyrrolidone which has been polymerized in aqueous solution, i.e. the loss of iodine is about 20% less.
The loss of available iodine in the aqueous solution during the storage test is substantially independent of the water content of the polyvinylpyrrolidone used and is substantially less than the loss in the comparative experiment. These results show the superiority of the polyvinylpyrrolidone, manufactured according to the invention, for the manufacture ~ ~-of PVP-I.
The formulations intended for the ultimate user can be manufactured from the PVP-I, ob-tained according to the invention, by conventional methods of the art, employing -the conventional pharmaceutical auxiliaries. Preferred forms of formulations are aqueous solutions which contain, as auxiliaries, e.g,, surfactants, alcohol, glycerol and buffer substances such as trisodium phosphate or sodium bicarbonate. These formulations can also be prepared with added hydrogen peroxide.
Other suitable formulations are soap solutions, shampoos, powders, gels and sprays.
' "' ' '"'; , ,
Claims (6)
1. A process for the manufacture of polyvinyl-pyrrolidone by polymerization of vinylpyrrolidone in an organic solvent in the presence of an organic per-compound, wherein anhydrous organic solvents are used and a heavy metal of atomic number from 23 to 29, in the form of a complex compound or of a salt with an organic acid, is added as a co-activator.
2. A process as claimed in claim 1, wherein the polymerization is carried out in benzene or an alkylbenzene.
3. A process as claimed in claim 1, wherein the polymerization is carried out in a monohydric aliphatic alcohol of 1 to 4 carbon atoms.
4. A process as claimed in claim 1, wherein the polymerization is carried out in isopropanol.
5. A process as claimed in claim 1, wherein a copper compound is used as the heavy metal compound.
6. A process as claimed in claim 1, wherein the amount of heavy metal compound added is from 0.01 to 10 ppm, based on the weight of the vinylpyrrolidone.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19742439196 DE2439196C3 (en) | 1974-08-16 | 1974-08-16 | Process for the production of polyvinylpyrrolidone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1057894A true CA1057894A (en) | 1979-07-03 |
Family
ID=5923266
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA233,155A Expired CA1057894A (en) | 1974-08-16 | 1975-08-08 | Manufacture of polyvinylpyrrolidone |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS5146388A (en) |
| BE (1) | BE832352A (en) |
| CA (1) | CA1057894A (en) |
| CH (1) | CH617214A5 (en) |
| DE (1) | DE2439196C3 (en) |
| ES (1) | ES440275A1 (en) |
| FR (1) | FR2281942A1 (en) |
| GB (1) | GB1513258A (en) |
| NL (1) | NL7508762A (en) |
| SE (1) | SE406914B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3642633A1 (en) * | 1986-12-13 | 1988-06-23 | Basf Ag | METHOD FOR PRODUCING VINYLPYRROLIDONE POLYMERISATS |
| DE19915420A1 (en) * | 1999-04-06 | 2000-10-12 | Basf Ag | Stabilized polyvinylpyrrolidone preparations |
| CN102603949B (en) * | 2011-12-22 | 2014-03-19 | 张家口市珂玛精细化工有限公司 | Method for preparing polyvinylpyrrolidone K30 by using low-purity vinylpyrrolidone |
-
1974
- 1974-08-16 DE DE19742439196 patent/DE2439196C3/en not_active Expired
-
1975
- 1975-07-22 NL NL7508762A patent/NL7508762A/en not_active Application Discontinuation
- 1975-08-08 CA CA233,155A patent/CA1057894A/en not_active Expired
- 1975-08-12 BE BE159133A patent/BE832352A/en not_active IP Right Cessation
- 1975-08-13 CH CH1055675A patent/CH617214A5/en not_active IP Right Cessation
- 1975-08-13 FR FR7525189A patent/FR2281942A1/en active Granted
- 1975-08-14 SE SE7509114A patent/SE406914B/en not_active IP Right Cessation
- 1975-08-14 ES ES440275A patent/ES440275A1/en not_active Expired
- 1975-08-15 JP JP9865075A patent/JPS5146388A/en active Pending
- 1975-08-15 GB GB3402075A patent/GB1513258A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| SE7509114L (en) | 1976-02-17 |
| JPS5146388A (en) | 1976-04-20 |
| NL7508762A (en) | 1976-02-18 |
| CH617214A5 (en) | 1980-05-14 |
| DE2439196B2 (en) | 1978-03-09 |
| ES440275A1 (en) | 1977-06-01 |
| DE2439196C3 (en) | 1978-11-02 |
| BE832352A (en) | 1976-02-12 |
| DE2439196A1 (en) | 1976-02-26 |
| FR2281942A1 (en) | 1976-03-12 |
| SE406914B (en) | 1979-03-05 |
| FR2281942B1 (en) | 1980-04-04 |
| GB1513258A (en) | 1978-06-07 |
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