Search Images Maps Play YouTube News Gmail Drive More »
Sign in
Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader.

Patents

  1. Advanced Patent Search
Publication numberUS2706701 A
Publication typeGrant
Publication dateApr 19, 1955
Filing dateApr 15, 1952
Priority dateApr 15, 1952
Publication numberUS 2706701 A, US 2706701A, US-A-2706701, US2706701 A, US2706701A
InventorsHosmer William Austin, Beller Hans
Original AssigneeGen Aniline & Film Corp
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Process for the preparation of iodinepolyvinylpyrrolidone by dry mixing
US 2706701 A
Abstract  available in
Images(3)
Previous page
Next page
Claims  available in
Description  (OCR text may contain errors)

United States Patent PROCESS FOR THE PREPARATION OF IODINE- POLYVINYLPYRROLIDONE BY DRY MIXING Hans Beller, Cranford, N. J., and William Austin Hosmer, Pittsfield, Mass., assignors to General Aniline & Film Corporation, New York, N. Y., a corporation of Delaware No Drawing. Application April 15, 1952, Serial No. 282,458

2 Claims. (Cl. 167--70) This invention relates to an improved process for preparing a dry powdered adduct of iodine and polymeric l-vinyl-2-pyrrolidone (hereinafter called polyvinylpyrrolidone) whereby a stable composition is formed which is readily soluble in water and which provides iodine in readily available and germicidally and bactericidally active form which is essentialy non-toxic to warmblooded animals.

In the copending application of Herman A. Shelanski, Serial No. 135,519, filed December 28, 1949, there is disclosed a novel composition of polyvinylpyrrolidone and iodine which has been found to be of substantial value for many applications in which advantage is taken of the bactericidal activity of the iodine but in which the irritating, sensitizing, and toxic properties of the iodine are substantially overcome. As disclosed in this application, this novel i0dine-polyvinylpyrrolidone composition may be prepared by adding a solution of iodine, such as Lugols solution or tincture of iodine to an aqueous solution of polyvinylpyrrolidone.

It has now been found that valuable compositions of iodine and polyvinylpyrrolidone can be prepared by thoroughly mixing dry elemental iodine with dry powdered polyvinylpyrrolidone. The iodine and powdered polymer may be mixed until a homogenous powder is obtained, the mixing being carried out in materials which are not attacked by iodine so as to avoid the introduction of metal ions into the finished composition. This mixing may be effected by grinding the iodine and polyvinylpyrrolidone in a mortar and pestle or more advantageously in a suitable mechanical mixer such as a ball mill. The time of mixing varies only with the efiiciency thereof, as the combination of the polyvinylpyrrolidone with iodine on its surface is rapid, in fact, such combination will occur to some extent on dropping iodine crystals on the dry powdered polymer.

On completion of the mixing there is obtained a compound in a physical state similar to the polymer alone but which contains varying proportions of iodineavailable iodine (as distinguished from free iodine), iodide ion, and bound iodine. A distinction between these forms may be made on an analytical basis, available iodine being determined directly by dissolving a sample of the product in water and titrating with 0.1-N sodium thiosulfate (NazSzOa), solution using starch as an indicator. The amount of iodine present as iodide ion is determined by reducing the iodine compound in solution with l-N sodium acid sulfite in a NaHSOs, adding enough to make the solution colorless, then adding 0.1-N silver nitrate and enough nitric acid to make the solution acidic and back-titrating with ammonium thiocyanate (NH4SCN). The iodide ion is the difference between this figure and the available iodine as determined above. The total iodine may be determined by combustion methods such as that formulated by Hallett in Scotts Standard Methods of Chemical Analysis, bound iodine then being determined by substracting the sum of available iodine and iodide ion from the total iodine as determined above.

The product obtained on mixing polyvinylpyrrolidone and iodine contains a total amount of iodine equal to the amount employed in making the composition and, as stated, this iodine is present as available iodine, iodide ion and bound iodine. It has been found that with any given sample of polyvinylpyrrolidone the amount of bound iodine is constant but that the iodine present as available iodine and iodide ion may vary somewhat. On

"ice

standing, the amount of available iodine slightly decreases which the amount of iodide ion increases. It has been found, however, that a stable product in which the ratio of available iodine to iodide ion is substantially 2:1 is readily and rapidly obtained by heating the dry blended material to a temperature of the order of 100 C. Higher temperatures are preferably avoided in order to avoid degradation of the polymer. Some slight stirring is advantageous during this heating in order to assure a uniform product. It has been found that the heating should be continued until the ratio of available iodine to iodide ion is substantially 2:1. It has been found that before heating one sample, it had a vapor pressure of 0.06 mm. at 55 C. After heating, the product had substantially no vapor pressure at 55 C. Thus, the heating completed the process of formation of a complex in which the iodine is chemically available but not free.

The details of the present invention will be apparent from the following specific examples in which the parts are by weight: By K value in these examples is meant Fikentscher K value (1000 k) as defined by H. Fikentsober-Cellulosechemie 13, 58-64, 71-4 (1932) and was determined with aqueous solutions of the polymer using an Ubbelohde viscosimeter at 25 C., the concentration being 1 gram of polymer (anhydrous basis) per 100 ml. of solution.

EXAMPLE I Twelve grams of dry polyvinylpyrrolidone having a K value of 90 (water content about 2 to 3 per cent) was added to 6 grams of solid iodine crystals in a glass bottle containing a few pebbles and beads. This was rolled for three days on a roller mill with occasional manual stirring to loosen the material caked on the sides of the bottle. Analysis showed that the thus obtained product contained 35.4 per cent total iodine and 31.91 per cent available iodine; The material was heat-treated at C. for 64 hours in a closed glass bottle with occasional stirring. On completion of this treatment, analysis showed that the material contained 35.3 per cent total iodine, 25.7 per cent available iodine.

EXAMPLE II EXAMPLE III An earthenware crock, having a capacity of one gallon, was charged with 832 grams of dry polyvinylpyrrolidone having a K value of 33 and 168 grams of crystalline iodine broken up in the form of small granules. Enough pebbles, approximately 30, were added to assure eificient mixing. The lid was clamped on tightly and the crock rotated on a roller mill for twenty-four hours. After this period, the mixture was homogenous and no iodine crystals were visible. The material was placed in an oven for eighteen hours at 200 F. (93 C.) with occasional mixing to assure homogeneity. After this treatment, analysis showed 10.2 per cent available iodine, 5.3 iodide ion. About 1.3 per cent thus was in the form of bound iodine, probably mainly combined with unsaturated links of the polymer (terminal unsaturation) and a small amount of residual monomer which may have been present therein. This product was stable and series of samples thereof which were maintained at F. and room temperature and tested at weekly intervals for available iodine and iodide ion over a period of six weeks showed no variation in available iodine and iodide ion.

In preparing the novel polyvinylpyrrolidone iodine compositions of the present invention, it has been found that from l-35 per cent total iodine can readily be combined with polyvinylpyrrolidone. It has further been found that the amount of iodine which should be mixed with polyvinylpyrrolidone in order to produce a product having any desired percentage of available iodine can readily be determined since it has been found that in order to obtain a product which is stable on storage, it is desirable that in the final product the ratio of available iodine to iodine ion be substantially 2:1. Thus, to produce a prodnot having any given desired percentage of available iodine, it is necessary to add to the polyvinylpyrrolidone, sufiicient iodine so that the available iodine is 65 per cent of the available iodine plus the iodide ion. In addition, enough iodine must be added to take care of the bound iodine. This bound iodine has been found to be uniform for any particular polymer regardless of how much total iodine is added; however, the bound iodine varies somewhat with individual batches of polymer. It has been found that the amount of iodine which must be allowed for mixing with any given polymer in order to provide for the bound iodine can readily be determined by simple preliminary tests, i. e., by addition of 0.0l-N iodine solution to an aqueous solution of the polymer and backtitrating with 0.1-N sodium thiosulfate solution using starch as an indicator.

EXAMPLE IV Three one-hundred-pound batches of polyvinylpyrrolidone iodine composition containing 10 per cent available iodine, per cent available iodine and 2 /2 per cent available iodine, respectively, were prepared. The ratio of iodine to polyvinylpyrrolidone in the charge was determined by adding a total amount of iodine, such that the available iodine would be 65 per cent of the available plus iodide ion and in addition enough iodine was added to take care of bound iodine. In the particular polymer employed, preliminary test showed that 1.3 per cent iodine was necessary and a corresponding allowance was therefore made.

The following is a table of the calculated amounts of iodine added to polyvinylpyrrolidone to prepare the above compositions, a sufficient amount of polyvinylpyrrolidone being used so that the total iodine required plus the amount of polyvinylpyrrolidone equal 100 pounds:

Monomer analysis of 0.65 per cent.

The iodine, which was crude iodine in the form of soft lumps, A" to 1" size, was charged in a 94-gallon ball mill along with 17 pounds of %l" pebbles. The iodine was ground for one hour at room temperature, at which time it was found that the iodine was approximately 40-80 mesh size. By visual observation no difference could be noticed in the size of the particles in one hour iodine and the 3-4 hour ground samples. The required amount of polyvinylpyrrolidone was then added to the ball mill and blending was continued for six hours at room temperature therein. The ball mill was opened after two hours of mixing and any crystals of iodine found around the gasket were scraped back into the mill. The speed of the ball mill for grinding was 16 R. P. M. The thus obtained blended polyvinylpyrrolidone iodine composition was placed in dryer trays, one-half full, and heated for a total time of twenty-two hours at a temperature of 95 C. (200 F.) in a closed tray dryer. After six, twelve, and eighteen hours on temperature, the dryer was opened and the trays were stirred with a glass rod. This was done so as to assure uniform product. The total actual heating time was eighteen hours, a total of four hours being consumed in stirring the polyvinylpyrrolidone iodine composition. With each stirring the dryer door was opened slowly to permit more rapid cooling and allowed to cool for twenty minutes. The dryer was then closed, the steam turned on. Approximately one-half hour was required to get the dryer back on temperature. The stabilized material, when discharged from the dryer, was placed in the ball mill with ten pounds of pebbles and mixed for ten hours. Samples of the blended product of the batches containing 5% and 2 /2 calculated available iodine were taken before heating and placed in a sealed glass jar. These jars were then heated for eighteen hours at 93 C. The analyses of the thus obtained products are given in the following table:

Table 11 Percent Percent Percent Av. Iodine+ Method 01 Heating vs. Iodide Total Av. Iodine+ Iodine Ion Iodine Iodide Ion Open Tray 9. 99 4. 77 14. 77 0. 677 Do 5. 08 2. 58 8.12 0. 663 Closed Jar 5. 16 2. 52 8. l4 0. 673 Open Tray.. 2. 86 1. 91 5. 50 0.600 Closed Jar 2. 96 2. 04 5. 33 0. 593

examples:

EXAMPLE V 832 parts of polyvinylpyrrolidone having a K value of 36 was charged to a ball mill along with 168 parts of iodine crystals and the mixture blended for six hours, the ball mill being opened after two hours of mixing, at which time any crystals of iodine found around the gasket were scraped back in the mill.

On completion of this mixing, 636 parts of the thus obtained ten per cent available iodine unstabilized polyvinylpyrrolidone iodine composition was diluted with 566 parts of polyvinylpyrrolidone and the mixture blended for six hours in the ball mill. The ratio of the ten per cent mixture of polyvinylpyrrolidone iodine composition to polyvinylpyrrolidone is 1:1.13 on a dry basis. This ratio of polyvinylpyrrolidone, before dilution, was used in order to obtain the normal nine per cent total iodine necessary in the preparation of a polyvinylpyrrolidone iodine compo sition having a final five per cent available iodine after stabilization.

430 parts of the unstabilized five per cent available iodine-polyvinylpyrrolidone composition, obtained as described immediately above, was subsequently diluted to produce a two and one-half per cent available iodinepolyvinylpyrrolidone composition. The same method was used as in diluting ten per cent available iodinepolyvinylpyrrolidone composition to prepare the five per cent available iodine-polyvinylpyrrolidone composition. By calculation, it was found that in order to obtain two and one-half per cent available iodine in the composition after stabilization, 5.1 per cent iodine should be present. Therefore, 320 parts of polyvinylpyrrolidone was charged along with the 330 parts of five per cent available iodinepolyvinylpyrrolidone composition and the materials were blended for six hours in the ball mill. The ratio of five per cent unstabilized mixture to polyvinylpyrrolidone, on the dry basis, is 111.39.

Samples of all three batches were heated at 93 C. for twenty hours in glass jars. On completion of this heating, each of the products was a brown powder which was readily soluble in water. On analysis for available iodine, iodide ion and total iodine the following analytical results were obtained.

Table III a Percent Percent Percent Ava. Iodine-.- Desred 53g AW Ava. Iodide Total Ava. Iodine-1- Iodine Ion Iodine Iodide Ion EXAMPLE VI Six pounds of dry polyvinyl pyrrolidone having a K value of 36 and three pounds of solid iodine crystals were placed in a ceramic ball mill containing three pounds of pebbles. The mill was closed and rolled for a total of 30 hours in an oven maintained at 200 F. The mill was removed from the oven three times during the course of the mixing and, after cooling to room temperature, the contents manually stirred to loosen material caked on the sides and top thereof. On completion of this treatment, analysis showed that the material contained 32.5 per cent total iodine, 20 per cent available iodine and 11 per cent iodide ion. The product was a homogeneous brown powder, soluble in water.

We claim:

1. The method of producing a stable polyvinylpyrrolidone-iodine composition which comprises thoroughly mixing elemental iodine and powdered polymeric 1 vinyl 2 pyirolidone and heating said mixture until the ratio of available iodine to iodide ion in said composition is 15 No. 8, pp.

substantially 2: 1.

UNITED STATES PATENTS 2,077,298 Zelger Apr. 13, 1937 2,121,029 Goedrich June 21, 1938 2,329,445 Turner Sept. 14, 1943 2,495,918 Bolton Jan. 31, 1950 OTHER REFERENCES Murat: Produits Pharmaceutiques, August 1949, vol. 4,

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US2077298 *Mar 16, 1935Apr 13, 1937Eastman Kodak CoProcess for the extraction of halogen from fluids
US2121029 *Dec 15, 1934Jun 21, 1938William R Warner & Co IncGermicides and processes for making the same
US2329445 *Mar 28, 1940Sep 14, 1943American Dairles IncThyroprotein and method of making the same
US2495918 *Aug 28, 1948Jan 31, 1950Du PontPoly-n-vinyl lactam photographic silver halide emulsions
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US2754245 *Sep 23, 1954Jul 10, 1956Gen Aniline & Film CorpInterhalogen adducts of polyvinyl pyrrolidone
US2826532 *Sep 22, 1954Mar 11, 1958Gen Aniline & Film CorpProcess of stabilizing polyvinyl pyrrolidone-iodine compositions
US2853416 *Sep 19, 1955Sep 23, 1958Gen Aniline & Film CorpMethod of protecting plants by applying a pesticidal amount of a polyvinylpyrrolidone-iodine adduct
US2853417 *Sep 19, 1955Sep 23, 1958Gen Aniline & Film CorpMethod of controlling plant pests with an iodine adduct of a copolymer of nu-vinyl pyrrolidone and a polymerizable vinyl compound containing one aliphatic double bond
US2900305 *Aug 9, 1956Aug 18, 1959Gen Aniline & Film CorpPreparation of iodine polyvinylpyrrolidone adducts
US2964447 *Apr 10, 1956Dec 13, 1960Gen Aniline & Film CorpPolymer-metal process
US2987505 *Mar 4, 1958Jun 6, 1961Gen Aniline & Film CorpCompositions of polymeric nu-vinyl-2-oxazolidone and halogens
US3028300 *Sep 13, 1960Apr 3, 1962West Laboratories IncGermicidal compositions and methods for preparing the same
US3087853 *Jul 2, 1956Apr 30, 1963Gen Aniline & Film CorpWater soluble compositions consisting essentially of iodine and a water soluble oxygen containing polymer
US3133904 *May 22, 1959May 19, 1964Dow Chemical CoMolecular complexes of halogen and cyclic carbamate
US3136755 *Dec 1, 1960Jun 9, 1964Gen Aniline & Film CorpInsoluble polymeric-iodine complexes
US3437647 *Mar 4, 1966Apr 8, 1969Gaf CorpHalogen adducts of alkylated polymers of heterocyclic n-vinyl monomers
US3898326 *May 14, 1973Aug 5, 1975West Laboratories IncPolyvinylpyrrolidone-iodide compositions and polyvinylpyrrolidone-iodide-iodine complexes prepared therefrom
US3958026 *Sep 11, 1974May 18, 1976Ciba-Geigy CorporationDisinfection and sterilisation of mussels, crustacea and fish
US4009326 *Jul 31, 1975Feb 22, 1977Gaf CorporationPhotoconductive polymer and method of manufacture
US4017407 *Jan 27, 1975Apr 12, 1977West Laboratories, Inc.Methods for preparing solid iodine carrier mixtures and solid formulations of iodine with iodine carriers
US4088597 *Jun 13, 1977May 9, 1978Deutsche Gold- Und Silber-Scheideanstalt Vormals RoesslerIodophor solution
US4094967 *Oct 22, 1976Jun 13, 1978Allor FoundationIodine-polyvinylpyrrolidone solid product and method of preparation
US4125602 *Sep 20, 1977Nov 14, 1978Ciba-Geigy CorporationProcess for the production of iodophors
US4200710 *Apr 17, 1979Apr 29, 1980Basf AktiengesellschaftPreparation of polyvinylpyrrolidone-iodine
US4214059 *Jun 12, 1978Jul 22, 1980The Purdue Frederick CompanyMethod for the production of iodophor powders
US4235884 *Mar 5, 1979Nov 25, 1980Nicolas SalkinMethod for the preparation of stable aqueous solutions of complexes of polyvinylpyrrolidone and of halogens and the solutions obtained thereby
US4345049 *Oct 3, 1980Aug 17, 1982Basf AktiengesellschaftPreparation of polyvinylpyrrolidone-iodine
US4402937 *Sep 19, 1980Sep 6, 1983Basf AktiengesellschaftPreparation of PVP-iodine
US4521403 *Dec 30, 1983Jun 4, 1985Simon Gilbert IChemotherapeutic method for treating periodontal disease
US4526751 *Dec 9, 1983Jul 2, 1985Gartner William JGermicidal solutions effective for solid surface disinfection
US4567036 *Mar 6, 1985Jan 28, 1986Simon Gilbert IChemotherapeutic method for treating periodontal disease, and composition therefore
US4594392 *Nov 1, 1985Jun 10, 1986Ametek, Inc. - Plymouth Products DivisionSynergistically stabilized mixed form halogenated and/or interhalogenated resins for disinfecting water
US4769013 *Jun 4, 1986Sep 6, 1988Hydromer, Inc.Bio-effecting medical material and device
US4849215 *Jan 9, 1987Jul 18, 1989Euroceltique, S.A.Pharmaceutical iodophor preparations with controlled iodine:iodide ratio and method of producing the same
US5152987 *Oct 8, 1991Oct 6, 1992Isp Investments Inc.Process for preparing water-insoluble PVP-iodine product
US5616348 *Nov 25, 1994Apr 1, 1997West Agro, Inc.Germicidal detergent-iodine compositions including polyvinyl pyrrolidone and compatible nonionic surfactant complexors
US5753699 *Oct 9, 1997May 19, 1998Medlogic Global CorporationMethods for treating non-suturable, superficial wounds by use of cyanoacrylate ester compositions comprising an antimicrobial agent
US5863556 *Jul 31, 1997Jan 26, 1999Euro-Celtique, S.A.Preparations for the external application of antiseptic agents and/or agents promoting the healing of wounds
US6090397 *Nov 3, 1997Jul 18, 2000Medlogic Global CorporationKits containing cyanoacrylate compositions comprising an antimicrobial agent
US6475502Jun 1, 2000Nov 5, 2002Flowers Park Ltd.Kits containing cyanoacrylate compositions comprising an antimicrobial agent
US6811771Apr 25, 2000Nov 2, 2004Ebara CorporationBactericidal organic polymeric material
US6852233Apr 25, 2000Feb 8, 2005Ebara CorporationMetal-collecting apparatus and method for elution and recovery of metal from metal-collecting material
US7297344May 27, 1999Nov 20, 2007Euro-Celtique, S.A.Preparations for the promotion of wound healing in the upper respiratory tract and/or ear
US7300667May 27, 1999Nov 27, 2007Euro-Celtique, S.A.Preparations for the application of anti-inflammatory, especially antiseptic agents and/or agents promoting the healing of wounds, to the lower respiratory tract
US7468194May 25, 2000Dec 23, 2008Euro-Celtique, S.A.Preparations for the application of anti-inflammatory agents
US20040230309 *Feb 13, 2004Nov 18, 2004Depuy Spine, Inc.In-situ formed intervertebral fusion device and method
DE1061075B *Sep 17, 1956Jul 9, 1959Gen Aniline & Film CorpVerfahren zur Herstellung von loeslichen Additionsprodukten aus Jod und Polymerisaten
DE2443530A1 *Sep 11, 1974Mar 27, 1975Ciba Geigy AgDesinfektion und entkeimung von muscheln, crustaceen und fischen
DE4013118A1 *Apr 25, 1990Oct 31, 1990Harbor Ucla Med Ct Res EducatPovidon-iod-mittel zur ophthalmischen antimikrobiellen prophylaxe bei neugeborenen
DE4013118C2 *Apr 25, 1990Apr 9, 1998Res & Education Inst IncVerwendung von Povidon-Iod zur ophthalmischen antimikrobiellen Prophylaxe bei Neugeborenen
WO1993006837A1 *Aug 21, 1992Apr 15, 1993Isp Investments IncProcess for preparing pvp-iodine product
WO2012003326A1Jun 30, 2011Jan 5, 2012Wright Medical Technology, Inc.Composition comprising calcium phosphate and sulfate powders and tri - calcium phosphate particles used in the treatment of degenerative bone conditions
WO2015089373A1Dec 12, 2014Jun 18, 2015Wright Medical Technology, Inc.Multiphasic bone graft substitute material
Classifications
U.S. Classification525/356, 523/122, 424/78.25, 424/78.7, 424/672, 424/78.2, 524/401, 524/548
International ClassificationA61K47/48, A61K33/18, C08F8/20, C08K3/26
Cooperative ClassificationA61K47/48176, A61K33/18, C08K3/26, C08F8/20
European ClassificationC08K3/26, A61K33/18, C08F8/20, A61K47/48K4