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WO1992004061A1 - Preservation antimicrobienne de plasma - Google Patents

Preservation antimicrobienne de plasma Download PDF

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Publication number
WO1992004061A1
WO1992004061A1 PCT/US1991/006243 US9106243W WO9204061A1 WO 1992004061 A1 WO1992004061 A1 WO 1992004061A1 US 9106243 W US9106243 W US 9106243W WO 9204061 A1 WO9204061 A1 WO 9204061A1
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WIPO (PCT)
Prior art keywords
povidone
iodine
plasma
nutrient
concentration
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PCT/US1991/006243
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English (en)
Inventor
Edward Shanbrom
Original Assignee
Edward Shanbrom
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Edward Shanbrom filed Critical Edward Shanbrom
Priority to AU85118/91A priority Critical patent/AU648823B2/en
Publication of WO1992004061A1 publication Critical patent/WO1992004061A1/fr
Priority to NO92921757A priority patent/NO921757L/no

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0082—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using chemical substances
    • A61L2/0088—Liquid substances
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/10—Preservation of living parts
    • A01N1/12—Chemical aspects of preservation
    • A01N1/122—Preservation or perfusion media
    • A01N1/124—Disinfecting agents, e.g. antimicrobials
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
    • A01N59/12—Iodine, e.g. iodophors; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/16—Blood plasma; Blood serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals

Definitions

  • This invention relates to the treatment and preservation of blood plasma and plasma derivatives and to the protection of technicians, nurses and physicians and of the ultimate recipient patient from infection by plasma-borne microbes.
  • Tissue cultures means cells and tissues grown or enhanced in culture media and the culture media per se, but not including nutrients intended for use in tissue cultures.
  • An examples of a cultured tissue is cultured skin tissue for use in burn victims.
  • Cells and cellular products prepared by standard biological and/or genetic engineering techniques are other examples of tissue cultures.
  • Laboratory reagents, standards and samples means reagents and standards produced from or comprising human or animal fluids.
  • Examples of such products are control sera and blood plasma chemistry controls.
  • Donor While the term “donor” is not usually applied to the individual from whom such samples are acquired, that term, “donor” will be used here in a more general sense to include the individual from whom any blood plasma is obtained for any purpose, and such term will be used to refer even to an unwilling donor.
  • the donor may be a mammal or the fetus of a mammal.
  • Povidone is used in the sense that it is used in the U.S. Pharmacopeia to identify polyvinyl pyrrolidone suitable for use in physiolog ⁇ ically acceptable solutions.
  • Molecular Iodine Compound The term "molecular iodine compound” is used in this patent to mean and include molecular iodine, I, diatomic iodine, I 2 , or a compound or a mixture of compounds which either comprises iodine available in molecular form, typically as diatomic I 2 , or which reacts with or in the presence of the sample to produce such iodine.
  • Povidone-iodine is the principal example of such compounds. Povidone-iodine.
  • Povidone-iodine is a complex of molecular iodine with polyvinyl pyrrolidone. Povidone-iodine complexes of the type under consideration have been described in the literature and are marketed by The Purdue-Frederick Co. When percent concentrations are referred to in connection with povidone-iodine, the percentage refers to the percent of povidone-iodine by weight, based upon the weight of the solution or material to which the povidone-iodine is added.
  • a 1 weight percent ( w /o) solution of povidone-iodine indicates that enough povidone-iodine has been dissolved to result in a concentration of l w /o povidone-iodine giving a concentration of 1000 ppm I 2 .
  • povidone-iodine is added as a solution, e.g. 10% solution in water, pH about 1.5, but it can be added as a powder or otherwise.
  • Povidone-iodine powder contains approximately 85% PVP, 10 % I 2 and 5%Iodide. A 10% solution of this powder contains 1 % free, available iodine. (Gershenfeld, Am. J. Surgery 94, 938 (1957)).
  • the ratio of polyvinyl pyrrolidone to iodine in the povidone-iodine product used in the experiments referred to hereinafter is 8.5 parts of povidone-iodine per 1 part of active iodine.
  • the product also contains about 0.5 parts of inactive iodine as iodide.
  • Typical stock solutions are 10% (10,000 ppm I 2 ), 5% (5,000 ppm I 2 ) and 1 % (100 ppm I 2 ).
  • additional povidone polyvinyl pyrrolidone
  • the concentration of povidone-iodine in such compositions means the concentration of povidone-iodine added as 8:5 to 1 PVP to I 2 povidone-iodine, i.e. 1000 ppm I 2 .
  • Nutrient refers to materials which are derived in whole or in part from animal sources, such as fetal bovine serum (FBS), or which may become contaminated from other sources with pathogenic microbes or toxin- or pyrogen-producing microbes.
  • FBS fetal bovine serum
  • Nutrient is distinct from tissue culture medium in that nutrient should be free of propagating microor ⁇ ganisms and, when incorporated in added to a tissue culture medium, provides nutritional components, e.g. minerals, amino acids, etc., to support propaga ⁇ tion of desired cellular components with which the medium is inoculated or which are maintained in the medium.
  • Viable refers to cells or microorganisms which are capable of replicating or reproducing such as, for example, tissue, bacteria, protozoa, etc, and virus which under favorable circumstances are capable of self-propagation.
  • Those at risk include the doctor, nurse or clinical technician who takes the sample, the technicians who handle the sample and who use the sample in conducting analyses and tests, those who handle the sampling and testing equipment and apparatus, and the entire chain of individuals who attend to the disposal of sampling apparatus and the like, from the individuals who pick up the used apparatus through those who ultimately dispose of the apparatus, usually in specially designed high temperature furnace.
  • the risk of contracting disease is especially great in the handling of pooled plasma.
  • All plasma pools contain infectious microbes and all who work with pooled plasma eventually contract one or more diseases from the plasma.
  • Every technician who has long-term exposure to pooled plasma in the early stages of processing, e.g. during the initial pooling, spin down, etc. will eventually become infected with hepatitis.
  • the risk of illness from pathogens borne in pooled plasma and the certainty that one will eventually become infected and, at least, become a carrier of pathogens is a long-standing problem in the blood banking industry for which no suitable solution has been forthcoming.
  • EBV Barr virus
  • CMV cytomegalovirus
  • Other pathogenic viruses to which health care workers, and those who handle blood plasma and fluid sampling and handling apparatus, are exposed include hepatitis and human immuno ⁇ deficiency virus (HIV) as well as a large number of less life-threatening viruses.
  • Cytomegalovirus probably the most ubiquitous of the pathogenic microorganisms found in animal fluids and tissues. CMV is frequently associated with, and may be a causative or contributing factor in, life threatening disease in individuals with suppressed immune systems, and can be a principal causative factor in pneumonia, neurological disorders, febrile illness, ocular disease and hepatitis. CMV infection is a serious limiting factor in the transfusion and plasma from one individual to another. Recipients of plasma run a serious risk of CMV infectious disease, the risk being multiplied where the immune system of the recipient is suppressed to prevent rejection of the foreign organ or cells, or where immunosuppression is present from natural causes.
  • Herpesviruses represent a very large group of viruses which are responsible for, or involved in, cold sores, shingles, a venereal disease, mononucleosis, eye infections, birth defects and probably several cancers. Three subfamilies are of particular importance.
  • the alpha subfamily includes HV 1 (herpes virus simplex 1) which causes cold sores, fever blisters, eye and brain infections, HV 2 (herpes virus simplex 2) which cause genital ulceration, and HV 3 (HV varicella zoster) which causes chicken pox, shingles and brain infections.
  • the beta subfamily includes HV 5, the principal member of which is CMV discussed above.
  • the gamma subfamily includes HV 4 (Epstein-Barr) which cause infectious mononucleosis and is involved in Burkitt's lymphoma and nasopharyngeal carcinoma.
  • Nutrient for tissue culture media always contains pathogenic organisms which, without removal or treatment, destroy or greatly impair the value of the nutrient in tissue cultures. It is, generally, impossible to define with precision the exact materials required to propagate a given cell line and, therefore, it is common practice to use media based upon or containing serum and to add nutrient serum as needed during the cell propagation.
  • Bovine serum from adult animals may be suitable in some instances, but fetal bovine serum (FBS)
  • FBS fetal calf serum
  • IBR immunosorbent intestinal filtration
  • PI 3 parainfluenza 3
  • pools of raw serum probably contain at least 10 4 infectious BVD virus particles per milliliter.
  • Serum filtration is a common step in reducing the load of infectious organisms in serum, but serum quality can be damaged by filtration if significant amounts of serum components are adsorbed to the filters or if macromolecules are sheared. Shearing of macromolecules during filtration occurs generally when tangential flow filtration is used and turbulence develops. It is currently very difficult to obtain reliable results on the removal of BVD viruses from serum using filtration.
  • iodine as an antiseptic dates back to 1839. It is used today for various medicinal purposes.
  • iodine complexes with either nonionic surfactants, eg, polyethylene glycol mono(nonylphenyl)ether, or poly(vinyl- pyrrolidone) (PVP).
  • nonionic surfactants eg, polyethylene glycol mono(nonylphenyl)ether, or poly(vinyl- pyrrolidone) (PVP).
  • PVP poly(vinyl- pyrrolidone)
  • Iodine and iodine-containing compounds and preparations are employed extensively in medicine, eg, as antiseptics, as drugs administered in different combinations in the prophylaxis and treatment of certain diseases, and as therapeutic agents in various thyroid dyscrasias and other abnormalities.
  • Iodine is a highly reactive substance combining with proteins partly by chemical reaction and partly by adsorption. Therefore its antimicrobial action is subject to substantial impairment in the presence of organic matter such as serum, blood, urine, milk, etc. However, where there is no such interference, non- selective microbicidal action is intense and rapid. A saturated aqueous solution of iodine exhibits anti-bacterial properties.
  • Medicinal povidone-iodine preparations include aerosol sprays, gauze pads, lubricating gels, creams, solutions, douche preparations, suppositories, gargles, perineal wash solutions, shampoos, and skin cleansers and scrubs.
  • Povidone-iodine preparation are applied topically to the skin and to membranes, e.g. vaginal membranes, and in infected wounds and surgical incisions.
  • An important solubilizing agent and carrier for iodine is polyvinyl pyrrolidone (PVP), one grade of which is identified as povidone USP.
  • PVP-iodine is widely used externally on humans as an antiseptic.
  • Such products are marketed as BetadineTM and IsodineTM.
  • Povidone- iodine products and the preparation of such products are described in U.S. Patents 2,707,701 , 2,826,532, and 2,900,305 to Hosmer and Siggia, assigned to GAF Corporation and in a number of GAF Corporation publications; see, e.g. Tableting with Povidone USP (1981) and PVP Polyvinylpyrrolidone (1982).
  • Povidone-iodine powder contains approximately 85% PVP, 10 % l 2 and 5%Iodide. A 10% solution of this powder contains 1 % free, available iodine. (Gershenfeld, Am. J. Surgery 94, 938 (1957)).
  • PVP polystyrene-maleic anhydride
  • the single most widely studied and best characterized PVP complex is that of PVP-iodine.
  • hydrogen triiodide forms a complex with PVP that is so stable that there is no appreciable vapor pressure. It is superior to tincture of iodine as a germicide.
  • This invention is embodied in, inter alia, a method of treating patients with blood plasma comprising the steps of collecting plasma from a donor, and thereafter infusing the plasma into the patient to be treated.
  • the improvement of this invention comprises the additional steps of mixing the plasma with molecular iodine compound to result in a concentration from 0.1 w /o to 2 o,
  • This invention is embodied in, inter alia, a method treating plasma- containing nutrient for culture media to prevent the propagation of microbes in tissue culture media.
  • the invention comprises the steps of mixing said plasma constituent of the nutrient, either neat or after mixing with other nutrient components, with molecular iodine compound to result in a concentra ⁇ tion of from 0.17o to 27o, preferably from about 0.257o to 0.57o (250 to 500 ppm I 2 ), and allowing contact of said nutrient with said molecular iodine compound for at least about one-half minute sufficient to inactivate or destroy infective pathogenic microorganisms and thereafter infusing the nutrient into a tissue culture medium.
  • This invention is embodied in, inter alia, an article of commerce, namely nutrient for use in tissue culture media.
  • the nutrient is serum- containing liquid containing iodine introduced as a povidone-iodine in a concentration of from 0.17o to 27o, preferably from about 0.257o to 0.57o (250 to 500 ppm I 2 ), sufficient to inactivate or destroy infective pathogenic microorganisms therein, said nutrient being free of both viable and viable microorganisms.
  • This invention is embodied in, inter alia, a method of controlling a cell line comprising adding povidone-iodine to the tissue culture nutrient which supports cell replication in a concentration of from 0.17o to 27o, preferably from about 0.257o to 0.57o (250 to 500 ppm I 2 ), based on the nutrient sufficient to arrest or inhibit the propagation of the cell line but insufficient to kill the cell line and harvesting the composition of interest after such composi ⁇ tion has been expressed by the cell line.
  • This invention is embodied in, inter alia, a method of purifying plasma by contacting the liquid to be purified into contact with solid povidone-iodine having sufficient surface area to expose the liquid to sufficient iodine on such surface to kill pathogenic organisms therein, and removing the liquid from contact with the solid povidone-iodine.
  • the method may further comprise reacting the surface of the solid povidone-iodine with iodine between uses to regenerate the iodine content thereof.
  • This invention is embodied in, inter alia, a method of treating a patient which comprises the step of collecting plasma from the patient or another, preserving the plasma by refrigeration or freezing, warming and, if the plasma is frozen, thawing the plasma, and infusing the biological material into the patient.
  • the plasma is treated with molecular iodine compound to result in a concentration from 0.17o to 27o, the preferred range being from about 0.257o to about 0.5 w /o, and allowing contact of said plasma with said molecular iodine compound for at least about one-half minute sufficient to inactivate or destroy infective pathogenic microbes.
  • the mixing of the plasma with povidone-iodine is carried out in three sub-steps, namely, first, introducing povidone-iodine into the plasma in a concentration of from about 0.1 to 27o, the preferred range being from about 0.257o to about 0.57o; second, maintaining the plasma in contact with the povidone-iodine for a period of about one-half minute or longer; and, third, again introducing povidone-iodine into the plasma in a concentration of from about 0.17o to 27o, the preferred range being from about 0.257o to about 0.57o.
  • This invention is embodied in, inter alia, a method of disinfecting plasma derivatives comprising treating plasma before separation of the compo ⁇ nents thereof with povidone-iodine into the plasma in a concentration of from about 0.17o to 27o, the preferred range being from about 0.257o to about 0.57o, preparing the derivative of the plasma from the preceding step and treating the derivative from the next preceding step with povidone-iodine into the plasma derivative in a concentration of from about 0.17o to 27o, the preferred range being from about 0.257o to about 0.57o.
  • a method of treating patients with plasma comprises the steps of collecting plasma from a donor, and thereafter infusing the plasma into the patient to be treated, with the improvement of mixing the plasma with povidone-iodine with added povidone to give a povidone to iodine ratio of at least about 12: 1, preferably from about 15: 1 to 30: 1 and optionally up to about 60: 1 , sufficient to result in an iodine concentration of from about 0.17o to about 27o, preferably from about 0.257o to 0.57o (250 to 500 ppm l 2 ), and allowing contact of said plasma with said povidone-iodine with added povidone to give a povidone to iodine ratio of at least about 12:1, preferably from about 15: 1 to 30: 1 and optionally up to about 60: 1, for at least about one-half minute sufficient to inactivate or destroy infective pathogenic microbes in the plasma before infusing the plasma into the patient.
  • nutrient for culture media is treated to prevent the propagation of microbes in tissue culture media by mixing said nutrient with povidone-iodine with added povidone to give a povidone to iodine ratio of at least about 12 to 1 , preferably from 17: 1 to 30:1, in a concentration to produce a povidone-iodine concentration of from about 0.17o to about 27o, preferably from about 0.257o to 0.57o (250 to 500 ppm I 2 ), and allowing contact of said nutrient with said povidone-iodine for at least about one-half minute sufficient to inactivate or destroy infective pathogenic microorganisms to thereby produce a nutrient which is free of both viable cells and viable microorganisms.
  • the invention is an article of commerce consisting essentially of nutrient free of viable cells and viable microbes for use in tissue culture media consisting essentially of serum-containing liquid containing iodine introduced as a povidone-iodine with added povidone to give a povidone to iodine ratio of at least about 12 to 1, preferably from 15:1 to 30: 1 , in an amount sufficient to produce a povidone-iodine concentration of from about 0.1 o to about 27o, sufficient to inactivate or destroy infective pathogenic microorganisms therein, said nutrient being free of both viable cells and viable microorganisms.
  • the povidone-iodine is preferably introduced sufficient to produce a povidone-iodine concentration of from about 0.257o to about 0.57o.
  • the invention is also embodied in a method of controlling a cell line by adding povidone-iodine with added povidone to give a povidone-iodine ratio of at least about 12: 1, preferably from about 15: 1 to 30: 1 and optionally up to about 60: 1, sufficient to protect the cell line from destruction, to the tissue culture nutrient that supports cell line replication in a concentration to produce a povidone-iodine concentration of from about 0.17o to about 27o, preferably from about 0.257o to 0.57o (250 to 500 ppm I 2 ), based on the media, sufficient to arrest or inhibit the propagation of the cell line but insufficient to kill the cell line and insufficient to prevent the cell line from expressing a composition and harvesting said composition after such composition has been expressed by the cell line.
  • Another embodiment of the invention is a method of disinfecting plasma derivatives comprising (a) treating plasma before separation of the components thereof with povidone-iodine with added povidone to give a povidone to iodine ratio of at least about 12 to 1 , preferably from 15: 1 to 30: 1 , in an amount sufficient to provide from about 0.17o to about 27o, preferably from about 0.257o to 0.57o (250 to 500 ppm I 2 ), povidone-iodine in the plasma, (b) preparing a derivative of the plasma from step (a), and (c) treating the derivative from step (a) with povidone-iodine to provide from about 0.17o to about 27o, preferably from about 0.257o to 0.57o (250 to 500 ppm l 2 ), povidone-iodine in the derivative.
  • a method of separation of plasma factors by alcohol fractionation in which the improvement comprises the addition of povidone-iodine to the plasma before fractionation, the povidone-iodine with added povidone to give a povidone to iodine ratio in the plasma of at least about 12 to 1, preferably from 15: 1 to 30: 1 , in concentrations to provide from about 0.017o to about 27o, preferably from about 0.257o to 0.57o (250 to 500 ppm l 2 ), povidone- iodine to give higher yields and sha ⁇ er differentiation is also disclosed.
  • the concentration in the plasma is preferably from about 0.257o to about 0.57o.
  • An improvement in a method of separation of plasma fractions by cryoprecipitation comprising the addition of povidone-iodine to the plasma before cryoprecipitation, the povidone-iodine with added povidone to give a povidone to iodine ratio in the plasma of at least about 12 to 1, preferably from 15: 1 to 30:1 , in concentrations to provide from about 0.017o to about 27o povidone-iodine to give higher yields and sha ⁇ er differentiation is also disclosed.
  • the concentration in the plasma is preferably from about 0.257o to about 0.57o.
  • Povidone' s known value as a plasma expander becomes an element in a greatly improved method of preparing plasma products which are also free of pathogenic organisms.
  • Plasma-derived products which are used in diagnostic tests without altering the test results, with the single exception of an increase in iodine, may be prepared from plasma or plasma derivatives treated as described.
  • molecular iodine compound e.g. povidone-iodine
  • povidone-iodine in the plasma in a concentration of from about 0.17o to 27o, the preferred range being from about 0.257o to about 0.57o
  • conventional diagnostic procedures may be followed without alteration to accommodate to the presence of the iodine.
  • Povidone-iodine is an effective preservative solution, used as described above, for plasma preparations used as laboratory standards.
  • Plasma is be treated in accordance with this invention by introducing molecular iodine, e.g. povidone-iodine, into the plasma in a concentration of from about 0.17o to 27o, the preferred range being from about 0.257o to about 0.57o in the plasma.
  • the povidone- iodine has a povidone to iodine ratio of at least about 12: 1, preferably from about 15: 1 to 30: 1 and optionally up to about 60: 1.
  • a 0.25 w /o concentration, for example, in plasma provides a total kill of bacteria, virus and other pathogenic organisms.
  • the microbe kill is effective before the iodine reacts with other reducing agents in the plasma to the extent of reducing or eliminating the microbial activity of iodine, and without altering the essential characteristics of plasma.
  • povidone-iodine renders the cryoprecipitation and subsequent separations, e.g. alcohol separa ⁇ tion of fibrinogen, fibronectin and the factors, e.g. Factor VIII, more complete, with a cleaner separation and a higher yield of factors, etc.
  • Pooled plasma processes are an important and essential part of the production of many plasma products, particularly those components and fractions which are found in low concentration in the plasma.
  • the risk of infection to workers and, potentially to users of the product increases as the number of donor-samples are pooled.
  • every large lot of pooled plasma carries a significant microbial contaminant load and presents a serious risk of infection to workers and technicians who are exposed to such products.
  • Pathogenic microbes in plasma and plasma products can be eliminated, without interference with other plasma treatment and processing procedures, by adding molecular iodine, e.g. povidone-iodine, into the plasma in a concentration of from about 0.17o to 27o, the preferred range being from about 0.257o to about 0.57o, preferably early in the process of collecting and pooling the plasma.
  • molecular iodine e.g. povidone-iodine
  • polyvinyl pyrrolidone alone, in the course of studying the present invention. It was discovered that polyvinyl pyrrolidone alone was capable of killing up to 5 logs of virus in body fluids. Whether or not there is a synergism vis-a-vis this anti-viricidal activity and the activity of iodine has not yet been determined.
  • Cryoprecipitate may be produced from individual donor plasma or from pooled plasma.
  • the risks of infection attendant to the preparation and use of cryoprecipitate-derived products are substantially eliminated by the present invention.
  • the cryoprecipitate may, in effect, be treated by the treatment of the whole plasma or the plasma, or both, from which the cryoprecipitate is derived.
  • the cryoprecipitate may be treated to kill bacteria and virus using tlk present invention.
  • Molecular iodine e.g. povidone-iodine, is introduced in a concentration of from about 0.17o to 27o, the preferred range being from about 0.257o to about 0.57o, into the plasma sufficient to kill the bacteria and virus.
  • the plasma is then frozen. When the resulting cryoprecipitate is thawed there is an increase in the yield of cryoprecipitate, fibrinogen, fibronectin and Factor VIII, and the product is free of microbes.
  • plasma fractions and plasmas from other species may be treated in a similar manner with povidone-iodine.
  • Plasma factors which are separated by alcohol fractionation are separated in higher yield and sha ⁇ er differentiation when the alcohol- containing fractionation liquid contains povidone-iodine.
  • the resulting fraction is free of microbic contamination.
  • Infective pathogenic microorganisms are inactivated when molecular iodine compound is added to fetal bovine serum (FBS) or to nutrient containing FBS.
  • FBS fetal bovine serum
  • the povidone-iodine is introduced into the FBS or the FBS-containing nutrient, or nutrient containing other serum, in an amount sufficient to result in a povidone-iodine concentration of from about 0.17o to 27o, the preferred range being from about 0.257 ⁇ to about 0.57o.
  • the molecular iodine compound is absorbed and does not interfere with culture growth after the nutrient is sold and shipped as an article of commerce and used in tissue or tissue culture media.
  • Povidone-iodine does not interfere with antibody function and, thus, can be used effective as a sterilizer for monoclonal antibodies and other genetically engineered products which result from processes which introduce the risk of infection by bacteria or virus.
  • This invention finds application in medicine and veterinary science.

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Abstract

L'invention décrit le traitement et la préservation de plasma, de dérivés de plasma au moyen de polyvidone iodé pour tuer les microbes pathogènes sans détruire l'efficacité du plasma.
PCT/US1991/006243 1990-09-04 1991-09-03 Preservation antimicrobienne de plasma WO1992004061A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU85118/91A AU648823B2 (en) 1990-09-04 1991-09-03 Antimicrobial preservation of plasma
NO92921757A NO921757L (no) 1990-09-04 1992-05-04 Antimikrobiell konswervering av plasma

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US57729590A 1990-09-04 1990-09-04
US577,295 1990-09-04

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WO1992004061A1 true WO1992004061A1 (fr) 1992-03-19

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PCT/US1991/006243 WO1992004061A1 (fr) 1990-09-04 1991-09-03 Preservation antimicrobienne de plasma

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EP (1) EP0498871A4 (fr)
JP (1) JPH05502241A (fr)
AU (1) AU648823B2 (fr)
CA (1) CA2072749A1 (fr)
WO (1) WO1992004061A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0559856A1 (fr) * 1991-09-03 1993-09-15 Edward Shanbrom Conservation antimicrobienne de plaquettes et de facteurs sanguins
EP0614368A4 (fr) * 1992-05-04 1994-04-12 Edward Shanbrom Sang de transfusion humain sans danger.
EP0605690A1 (fr) * 1992-06-29 1994-07-13 Edward Shanbrom Conservation de sang, de tissus et de fluides biologiques dans du peroxyde d'hydrogene et du povidone
US5591350A (en) * 1994-04-15 1997-01-07 Pall Corporation Iodine disinfection method using a gaseous iodine treated porous medium
US6096216A (en) * 1994-06-09 2000-08-01 American National Red Cross Iodinated matrices for disinfecting biological fluids
US6106773A (en) * 1998-09-24 2000-08-22 American National Red Cross Pathogen inactivating compositions for disinfecting biological fluids
CN104304237A (zh) * 2014-11-11 2015-01-28 成都美强兽医技术服务有限公司 一种安全高效的动物精液消毒剂及其制备方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4114668B2 (ja) 2005-03-25 2008-07-09 エプソンイメージングデバイス株式会社 表示装置

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US4567036A (en) * 1983-12-30 1986-01-28 Simon Gilbert I Chemotherapeutic method for treating periodontal disease, and composition therefore
US4582052A (en) * 1982-03-23 1986-04-15 Repromed, Inc. Povidone-iodine dispensing fiber
US4959319A (en) * 1985-08-01 1990-09-25 Skelnik Debra L Process of corneal enhancement
US4971760A (en) * 1986-03-10 1990-11-20 University Of Southern California Novel method for disinfecting red blood cells, blood platelets, blood plasma, and optical corneas and sclerae

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US4582052A (en) * 1982-03-23 1986-04-15 Repromed, Inc. Povidone-iodine dispensing fiber
US4567036A (en) * 1983-12-30 1986-01-28 Simon Gilbert I Chemotherapeutic method for treating periodontal disease, and composition therefore
US4959319A (en) * 1985-08-01 1990-09-25 Skelnik Debra L Process of corneal enhancement
US4971760A (en) * 1986-03-10 1990-11-20 University Of Southern California Novel method for disinfecting red blood cells, blood platelets, blood plasma, and optical corneas and sclerae

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Title
Jo Bone Jt. Surg., Volume 58A, No. 1, issued 1976, DAVID O. SCHERR et al., "In Vitro Baderiological Evaluation of the Effectiveness of Antimicrobial Irrigating solutions", see pages 119 and 121. *
M.E. ABDULLAH et al., "Influence of Biological fluids on the Release of 125 I from Povidone - Inodine", 1981, see pages 828-830. *
Proceedings of the International Symposium on Povidone, W.W. BOND et al., "Observations of the Sporicidal, Bactericidal, and Virucidal Activity of Iodophours", 1983, See pages 167-177. *
See also references of EP0498871A4 *

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0559856A1 (fr) * 1991-09-03 1993-09-15 Edward Shanbrom Conservation antimicrobienne de plaquettes et de facteurs sanguins
EP0559856A4 (en) * 1991-09-03 1993-11-10 Edward Shanbrom Antimicrobial preservation of platelets and blood factors
EP0614368A4 (fr) * 1992-05-04 1994-04-12 Edward Shanbrom Sang de transfusion humain sans danger.
EP0614368A1 (fr) * 1992-05-04 1994-09-14 Edward Shanbrom Sang de transfusion humain sans danger
EP0605690A1 (fr) * 1992-06-29 1994-07-13 Edward Shanbrom Conservation de sang, de tissus et de fluides biologiques dans du peroxyde d'hydrogene et du povidone
EP0605690A4 (fr) * 1992-06-29 1994-12-07 Edward Shanbrom Conservation de sang, de tissus et de fluides biologiques dans du peroxyde d'hydrogene et du povidone.
US5591350A (en) * 1994-04-15 1997-01-07 Pall Corporation Iodine disinfection method using a gaseous iodine treated porous medium
US6096216A (en) * 1994-06-09 2000-08-01 American National Red Cross Iodinated matrices for disinfecting biological fluids
US6106773A (en) * 1998-09-24 2000-08-22 American National Red Cross Pathogen inactivating compositions for disinfecting biological fluids
CN104304237A (zh) * 2014-11-11 2015-01-28 成都美强兽医技术服务有限公司 一种安全高效的动物精液消毒剂及其制备方法
CN104304237B (zh) * 2014-11-11 2016-04-06 成都美强兽医技术服务有限公司 一种安全高效的动物精液消毒剂及其制备方法

Also Published As

Publication number Publication date
AU8511891A (en) 1992-03-30
EP0498871A1 (fr) 1992-08-19
JPH05502241A (ja) 1993-04-22
EP0498871A4 (en) 1994-05-18
AU648823B2 (en) 1994-05-05
CA2072749A1 (fr) 1992-03-05

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