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Publication numberUS2826532 A
Publication typeGrant
Publication dateMar 11, 1958
Filing dateSep 22, 1954
Priority dateApr 15, 1952
Publication numberUS 2826532 A, US 2826532A, US-A-2826532, US2826532 A, US2826532A
InventorsWilliam A Hosmer
Original AssigneeGen Aniline & Film Corp
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Process of stabilizing polyvinyl pyrrolidone-iodine compositions
US 2826532 A
Abstract  available in
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Claims  available in
Description  (OCR text may contain errors)

PROCESS OF STABILIZING POLYVINYL PYRROLI- DONE-IODINE COMPOSITIONS William A. Hosmer, Pittsiield, Mass., assignor to General Aniline & Film Corporation, New York, N. Y., a corporation of Delaware No Drawing. Application September 22, 1954 Serial No. 457,777

1 Claim. (Cl. 16770) This invention relates to a process of stabilizing a dry powdered adduct of iodine and polymeric 1-vinyl-2- pyrrolidone (hereinafter referred to as polyvinyl pyrrolidone) whereby a stable composition is obtained which when dissolved in water will not change its pH and maintain a constant available iodine content.

In the copending application of Herman A. Shelanski, Serial No. 135,519, filed December 28, 1949, now abandonded, there is disclosed a novel composition of polyvinyl pyrrolidone 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 iodine-polyvinyl pyrrolidone composition may be prepared by adding a solution of iodine, such as Lugols solution or tincture of iodine to an aqueous solution of polyvinyl pyrrolidone followed by dessication in a suitable dryer.

To improve on the method of preparing the foregoing novel iodine-polyvinyl pyrrolidone composition, there is disclosed in the copending application of Hans Beller and W. A. Hosmer, Serial No. 282,458, filed April 15, 1952, now U. S. Patent 2,706,701, a process whereby dry elemental iodine is mixed with dry powdered polyvinyl pyrrolidone. The iodine and powdered polymer is mixed until a homogeneous 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 is effected by grinding the iodine and polyvinyl pyrrolidone 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 efficiency thereof, as the combination of the polyvinyl pyrrolidone 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 available 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 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, 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. The iodide ion is the difierence 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 Method of Chemical Analysis, bound iodine then being determined by subtracting the sum of available iodine and iodide ion from the total iodine as determined above.

The product thus obtained may have an available iodine content ranging from 845% and an iodide ion content from 0.98 to 5.6%. With any given sample of polyvinyl pyrrolidone, the iodine present as available iodine and iodide ion may vary somewhat. On standing, the amount of available iodine slightly decreases while the amount of iodide ion increases. in order to obtain a stable product, Hans Beller et al. referred to above found that a 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 in the order of -490 C. Further details regarding this process may be obtained by reference to their patent, the contents of which are incorporated herein by reference, especially, the various iodine-polyvinyl pyrrolidone compositions as prepared in accordance with their Examples 1 to V1 inclusive.

The iodine-polyvinyl pyrrolidone compositions prepared in accordance with the aforestated application form aqueous solutions which contain iodine having a very high germicidal activity. The iodine-polyvinyl pyrrolidone composition in aqueous solution has a high acid reaction near a pH of 2, which in some instances, such as, for intravenous use or application on sensitive tissue necessitates the adjustment of such solution to near neutrality. Solutions so adjusted by alkaline agents, especially sodium bicarbonate have a tendency to lose their available iodine activity quite rapidly because of the shift of the hydrolysis equation to the right under increasingly alkaline conditions.

When aqueous solutions of iodine-polyvinyl pyrrolidone compositions are prepared and the pH adjusted to neutrality by the addition of sodium bicarbonate, the available iodine content decreases and the available iodide ion increases upon storage within a few weeks, thus posing a serious problem when shipping such solutions to hospitals and physicians. From the time the actual solution is made at the dispensing plant and the time at which it arrives in the hospital or physicians oflice, which may require several weeks, the solution loses potency in the available iodine content.

I have discovered that the tendency of the iodine-polyvinyl pyrrolidone composition to lose its available iodine content when prepared in aqueous solution. can be very readily overcome by blending 16 to 20 parts by weight of sodium bicarbonate per parts by weight of the iodine-polyvinyl pyrrolidone composition having an available iodine content from 8 to 15% and an available iodide ion content from 0.98 to 5.6% for a period of time ranging from 6 to 36 hours. The resulting product is stable and will readily dissolve in water to form essentially neutral solutions (having a pH range from 6.6 to 6.9). By this procedure, the iodine-polyvinyl pyrrolidone composition is made in a more available and readily useful form for injections and use on mucous tissue.

It is indeed wholly surprising and unexpected that the reaction indicated by the above equation has been found not to occur in the solid state when sodium bicarbonate is blended with the iodine-polyvinyl pyrrolidone composition even though moisture may be present either in the sodium bicarbonate or the iodine polyvinyl pyrrolidone composition, or both. More surprising is the fact that the solid mixture of iodine-polyvinyl pyrrolidone composition and sodium bicarbonate has the same stability as the dry iodine-polyvinyl pyrrolidone composition alone.

The following example will serve to illustrate how the stabilized iodinepolyvinyl pyrrolidone composition may be prepared in accordance with the present invention. It is to be understood, however, that this example is merely Example I To 100 parts of iodine-polyvinyl pyrrolidone composition (made by dry-blending 83.2 parts of polyvinyl pyrrolidone having a K value of 30 and 16.8 parts of iodine for 24 hours, followed by 24 hours of heating at 93 C.) there were added 10 parts of anhydrous sodium bicarbonate. The mixture was blended for 24 hours in a rotating glass vessel to insure uniformity. The product was made up as a 1% aqueous solution and had a pH of 6.7 to 6.9. In aging the dry product for six weeks at 100 F. no change in pH was observed, and no change in the available iodine and iodide ion content was noted.

For comparison a 1% aqueous solution of the iodinepolyvinyl pyrrolidone composition utilized above, i. e. prior to blending with sodium bicarbonate (having a pH of 2) and adjusted by the addition of anhydrous sodium bicarbonate to a pH of 6.6 to 6.7, the amount of bicarbonate added was not calculated, but made with vigorous stirring with the pH metered electrodes immersed in the solution. In aging this solution at 100 F. for six weeks, the pH increased from 6.6 to 7.4 and the available iodine content decreased from 11.84 to 11.3%, and the iodide content increased from 3.9 to 4.51%.

By blending sodium bicarbonate with the iodine-polyvinyl pyrrolidone composition, the resulting blend may be packaged as one stable unit and immediately utilized without further compounding. This expedient saves a considerable amount of money in packaging and shipping.

I claim:

The method of forming an aqueous iodine-polyvinylpyrrolidone composition which is stable with respect to a change in pH and loss in available iodine content, which comprises blending anhydrous sodium bicarbonate with dry iodine-polyvinyl-pyrrolidone composition until a uniform mixture is obtained, and dissolving the said mixture in water.

References Cited in the file of this patent UNITED STATES PATENTS OTHER REFERENCES Chemical Week, 69:25, Dec. 22, 1951, p. 19.

C and E N (Chem. and Eng. News), Feb. 19, 1951,

p. 664, New Iodine Compound.

Ridge et al.: Control of pH in Bleaching, Textile Manufacturer, July 1942, p. 282.

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US1557266 *Dec 27, 1922Oct 13, 1925Us Ind Alcohol CoComposition adapted to generate free iodine
US1841694 *May 16, 1930Jan 19, 1932Eimer & AmendTherapeutic iodine solution
US2386252 *Feb 21, 1942Oct 9, 1945Mendelsohn MajerAntiseptic composition
US2706701 *Apr 15, 1952Apr 19, 1955Gen Aniline & Film CorpProcess for the preparation of iodinepolyvinylpyrrolidone by dry mixing
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US3028300 *Sep 13, 1960Apr 3, 1962West Laboratories IncGermicidal compositions and methods for preparing the same
US3620773 *Apr 3, 1969Nov 16, 1971Gabriel Robert PMethod for treating harvested nonchlorophylleous produce
US3898326 *May 14, 1973Aug 5, 1975West Laboratories IncPolyvinylpyrrolidone-iodide compositions and polyvinylpyrrolidone-iodide-iodine complexes prepared therefrom
US4094967 *Oct 22, 1976Jun 13, 1978Allor FoundationIodine-polyvinylpyrrolidone solid product and method of preparation
US4200710 *Apr 17, 1979Apr 29, 1980Basf AktiengesellschaftPreparation of polyvinylpyrrolidone-iodine
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
US4320114 *Aug 27, 1980Mar 16, 1982Basf AktiengesellschaftManufacture of aqueous polyvinylpyrrolidone-iodine solutions
US4401651 *Jul 22, 1980Aug 30, 1983Knutson Richard AWound-healing compositions containing povidone-iodine
US4402937 *Sep 19, 1980Sep 6, 1983Basf AktiengesellschaftPreparation of PVP-iodine
US4408001 *Apr 6, 1981Oct 4, 1983The Dow Chemical CompanyDegeneration inhibited sanitizing complexes
US4481167 *Jul 1, 1981Nov 6, 1984The Dow Chemical CompanySanitizing complexes of polyoxazolines or polyoxazines and polyhalide anions
US4844898 *Aug 4, 1987Jul 4, 1989Kowa Co., Ltd.Wound-healing preparations
US5709851 *May 16, 1994Jan 20, 1998Euro-Celtique, S.A.Pharmaceutical iodine compositions with reduced irritancy
US5753699 *Oct 9, 1997May 19, 1998Medlogic Global CorporationMethods for treating non-suturable, superficial wounds by use of cyanoacrylate ester compositions comprising an antimicrobial agent
US5916581 *Oct 21, 1997Jun 29, 1999West Agro, Inc.Iodine antimicrobial compositions containing nonionic surfactants and halogen anions
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
US9320614May 28, 2015Apr 26, 2016DePuy Synthes Products, Inc.Spinal fusion implant
US9333091Apr 13, 2015May 10, 2016DePuy Synthes Products, Inc.In-situ formed intervertebral fusion device and method
US9387091Dec 18, 2014Jul 12, 2016DePuy Synthes Products, Inc.Spinal fusion implant
US9439776Mar 6, 2015Sep 13, 2016DePuy Synthes Products, Inc.In-situ formed intervertebral fusion device and method
US9439777Mar 31, 2015Sep 13, 2016DePuy Synthes Products, Inc.In-situ formed intervertebral fusion device and method
US9713538Jun 14, 2016Jul 25, 2017DePuy Synthes Products, Inc.Spinal fusion implant
US9724207Nov 6, 2015Aug 8, 2017DePuy Synthes Products, Inc.In-situ formed intervertebral fusion device and method
US9730803Feb 26, 2015Aug 15, 2017DePuy Synthes Products, Inc.Method of in-situ formation of an intervertebral fusion device
US9737413Oct 24, 2016Aug 22, 2017DePuy Synthes Products, Inc.Spinal fusion implant
US9788963Oct 19, 2015Oct 17, 2017DePuy Synthes Products, Inc.In-situ formed intervertebral fusion device and method
US9801725Jul 25, 2016Oct 31, 2017DePuy Synthes Products, Inc.Aspirating implants and method of bony regeneration
US9801729Mar 25, 2015Oct 31, 2017DePuy Synthes Products, Inc.In-situ formed intervertebral fusion device and method
US9808351Oct 6, 2015Nov 7, 2017DePuy Synthes Products, Inc.In-situ formed intervertebral fusion device and method
US9814589Sep 17, 2015Nov 14, 2017DePuy Synthes Products, Inc.In-situ formed intervertebral fusion device and method
US9814590Oct 19, 2015Nov 14, 2017DePuy Synthes Products, Inc.In-situ formed intervertebral fusion device and method
US20040074847 *Oct 16, 2002Apr 22, 2004Jaquess Percy A.Stable N-bromo-2-pyrrolidone and methods to make the same
US20040230309 *Feb 13, 2004Nov 18, 2004Depuy Spine, Inc.In-situ formed intervertebral fusion device and method
US20080172032 *Jan 11, 2007Jul 17, 2008James Pitzer GillsMethod for preventing tissue damage associated with irrigation of tissue with an antimicrobial solution
CN102093279A *Jan 7, 2011Jun 15, 2011上海宇昂化工科技发展有限公司High-stability nonionic N-vinyl butyrate lactam iodine and preparation method thereof
CN102093279BJan 7, 2011May 23, 2012上海宇昂化工科技发展有限公司High-stability nonionic N-vinyl butyrate lactam iodine and preparation method thereof
EP2987507A1Jun 30, 2011Feb 24, 2016Agnovos Healthcare, LLCMethods of treating degenerative bone conditions
WO1999020107A1 *Aug 6, 1998Apr 29, 1999West Agro, Inc.Improved iodine antimicrobial compositions containing nonionic surfactants and halogen anions
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
U.S. Classification524/548, 424/78.25, 424/672, 424/78.2
International ClassificationA61K47/48, A61K33/18, C08K3/26, C08F8/20
Cooperative ClassificationC08F8/20, A61K47/48176, A61K33/18, C08K3/26
European ClassificationA61K33/18, C08K3/26, C08F8/20, A61K47/48K4