WO2003035238A2 - Procedes de lutte contre le bioterrorisme - Google Patents

Procedes de lutte contre le bioterrorisme Download PDF

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Publication number
WO2003035238A2
WO2003035238A2 PCT/US2002/031584 US0231584W WO03035238A2 WO 2003035238 A2 WO2003035238 A2 WO 2003035238A2 US 0231584 W US0231584 W US 0231584W WO 03035238 A2 WO03035238 A2 WO 03035238A2
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WIPO (PCT)
Prior art keywords
radiation
kgy
moisture content
total dose
effective
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PCT/US2002/031584
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English (en)
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WO2003035238A3 (fr
Inventor
David M. Mann
William N. Drohan
Glenn Calvert
Martin J. Macphee
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Clearant, Inc.
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Priority to AU2002356540A priority Critical patent/AU2002356540A1/en
Publication of WO2003035238A2 publication Critical patent/WO2003035238A2/fr
Publication of WO2003035238A3 publication Critical patent/WO2003035238A3/fr

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    • 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
    • A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
    • A61L2/08—Radiation
    • A61L2/087—Particle radiation, e.g. electron-beam, alpha or beta radiation
    • 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
    • A61L2/0011—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 physical methods
    • 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
    • A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
    • A61L2/08—Radiation
    • A61L2/081—Gamma radiation
    • 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
    • A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
    • A61L2/08—Radiation
    • A61L2/082—X-rays
    • 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
    • A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
    • A61L2/08—Radiation
    • A61L2/084—Visible light
    • 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
    • A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
    • A61L2/08—Radiation
    • A61L2/085—Infrared radiation
    • 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
    • A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
    • A61L2/08—Radiation
    • A61L2/10—Ultraviolet radiation

Definitions

  • the present invention relates to methods for combating bio-terrorism. More specifically, the present invention relates to methods for combating bio-terrorism by irradiating a material, such as a letter or package or currency, to reduce the level of one or more biological contaminants or pathogens that may be present on or in the material, such as viruses, bacteria (including inter- and intracellular bacteria, such as mycoplasmas, ureaplasmas, nanobacteria, chlamydia, rickettsias), yeasts, molds, fungi, single or multi- cellular parasites, and/or prions or similar agents responsible, alone or in combination, for TSEs.
  • viruses including inter- and intracellular bacteria, such as mycoplasmas, ureaplasmas, nanobacteria, chlamydia, rickettsias
  • yeasts including inter- and intracellular bacteria, such as mycoplasmas, ureaplasmas, nanobacteria, chlamydia, ricketts
  • Bio-terrorism involves the use of biological contaminants or pathogens as weapons of terror, designed to spread fear throughout a given population. Moreover, bio-terrorism can result in political instability, particularly in view of the panic that many fast-moving plagues have historically engendered.
  • the extreme potency and virulence of such biological contaminants and pathogens means that as little as a few kilograms can be devastatingly effective (for example, it takes as few as 8000 inhaled anthrax spores to have a lethal effect on a human).
  • relatively large amounts of many biological contaminants and pathogens can be prepared from a small freeze-dried seed culture in a period of days to weeks.
  • Bio-terrorism is a lot easier to conduct and is thought by many experts to be much more likely to occur in the next few years than a replay of the terrorist tragedies of September 11, 2001.
  • a small cloud of bacteria or viruses could easily and silently infect tens of thousands of people, triggering fatal outbreaks of anthrax, smallpox, pneumonic plague or any of a dozen other deadly diseases.
  • victims infected with contagious ailments could pass the microbes to thousands of others before doctors even figured out what was going on, if ever given that there are still natural outbreaks of certain diseases such as plague.
  • Bio-terrorism is not new. Fourteenth-century barbarians tossed plague-infected corpses over the walls of fortified cities to spread the deadly infection among their enemies. In 1763, the English at Fort Pitt, Pa., gave smallpox-laden blankets to Indians who had been loyal to the French. And, as recently as the mid-1990s, U.N. weapons inspectors discovered that Iraq had stockpiled warheads containing anthrax spores and the toxin that causes botulism.
  • Biological attacks can be far more difficult to respond to than conventional terrorist attacks. For one thing, they tend to be covert rather than overt; and so for days, no one might know that such an attack had even occurred. That's a huge problem for a disease like anthrax. Up to 80 percent of people infected by inhaled spores die within days if untreated. By the time symptoms appear — fever, rash and congested lungs — it's generally too late.
  • a Clinton administration bio-terrorism initiative administered jointly by the CDC and the National Institutes of Health, is speeding development of protective technologies, including portable DNA diagnostic devices that may someday help identify mystery microbes raining from the sky. But the initiative's $300 million budget is probably only a fraction of what will be needed to protect the nation in years to come.
  • the CDC has contracted with two biotech companies to make and stockpile 40 million doses of smallpox vaccine.
  • the first batches that could be used by civilians are not expected to be ready, however, until some time in 2004.
  • ethylene oxide treatment is not suitable for use with letters and packages or currency because it leaves a toxic residue on the treated material.
  • Ethylene oxide treatment also requires that the letters and packages or currency be gas permeable and stable at temperatures above 100°C.
  • many potential treatments for reducing the level of active biological contaminants or pathogens can be easily defeated by bio-terrorists.
  • treatment with steam and/or ethylene oxide can all be rendered ineffective by enclosing the active biological contaminant or pathogen in a foil pouch (that could be opened or punctured when the letter or package was opened) or simply using an envelope that is not porous. Treatment with steam may also have a deleterious effect on inks.
  • Gas plasma sterilizers can be defeated by the presence of paper or other forms of cellulose.
  • An object of the invention is to solve at least the related art problems and disadvantages, and to provide at least the advantages described hereinafter.
  • a first embodiment of the present invention is directed to a method for combating bio-terrorism involving the presence of active biological contaminants or pathogens in or on a material, said method comprising irradiating said material with radiation for a time and at a rate effective to reduce the level of active biological contaminants or pathogens in or on said material.
  • Another embodiment of the present invention is directed to a method for combating bio-terrorism involving the presence of active biological contaminants or pathogens in or on a material, said method comprising: (i) performing at least one stabilizing process on said material, said stabilizing process selected from the group consisting of: (a) applying to said material at least one stabilizer in an amount effective to protect said material from said radiation; (b) placing said material in a container and reducing the moisture content of the atmosphere inside said container to a level effective to protect said material from said radiation; (c) reducing the temperature of said material to a level effective to protect said material from said radiation; (d) placing said material in a container and reducing the oxygen content of the atmosphere inside said container to a level effective to protect said material from said radiation; and (e) applying to said material at least one solvent in an amount effective to protect said material from said radiation; and (ii) i ⁇ adiating said material with a suitable radiation for a time and at a rate effective to reduce the level of active biological contaminants or pathogens in or on said material.
  • Another embodiment of the present invention is directed to a method for combating bio-terrorism involving the presence of active biological contaminants or pathogens in or on material, said method comprising: (i) performing at least two stabilizing process on said material, said stabilizing processes selected from the group consisting of: (a) applying to said material at least one stabilizer; (b) placing said material in a container and reducing the moisture content of the atmosphere inside said container; (c) reducing the temperature of said material; (d) placing said material in a container and reducing the oxygen content of the atmosphere inside said container; and (e) applying to said material at least one solvent; and (ii) irradiating said material with a suitable radiation for a time and at a rate effective to reduce the level of active biological contaminants or pathogens in or on said material, wherein said at least two stabilizing processes are together effective to protect said material from said radiation and further wherein said at least two stabilizing processes may be performed in any order.
  • biological contaminant or pathogen is intended to mean a contaminant or pathogen that, upon direct or indirect contact with a mammal, particularly a human, may have a deleterious effect on that mammal.
  • biological contaminants or pathogens include the various viruses, bacteria (including inter- and intracellular bacteria, such as mycoplasmas, ureaplasmas, nanobacteria, chlamydia, rickettsias), yeasts, molds, fungi, single or multi-cellular parasites, and/or prions or similar agents responsible, alone or in combination, for TSEs, all of which are known to those of skill in the art to be potentially employed as agents of bio-terrorism.
  • viruses such as human immunodeficiency viruses and other retroviruses, herpes viruses, filoviruses, circoviruses, paramyxoviruses, cytomegaloviruses, hepatitis viruses (including hepatitis A, B and C and variants thereof), pox viruses, toga viruses, Epstein-Barr viruses, parvoviruses, Ebola virus, smallpox virus, Venezuelan equine encephalitis virus, brucellosis and viruses causing Viral Haemorrhagic Fever; bacteria (including mycoplasmas, ureaplasmas, nanobacteria, chlamydia, rickettsias, including those responsible for Q fever and typhus), such as Escherichia, Bacillus, including B.
  • viruses such as human immunodeficiency viruses and other retroviruses, herpes viruses, filoviruses, circoviruses, paramyxoviruses, cytomegal
  • anthracis Yersinia, including Y. pestis, Campylobacter, Streptococcus and Staphylococcus; parasites, such as Trypanosoma and malarial parasites, including Plasmodium species; yeasts; molds; tularemia; and prions, or similar agents, responsible alone or in combination for TSE (transmissible spongiform encephalopathies), such as scrapie, kuru, BSE (bovine spongiform encephalopathy), CJD (Creutzfeldt-Jakob disease), Gerstmann-Straeussler-Scheinkler syndrome, and fatal familial insomnia.
  • active biological contaminant or pathogen is intended to mean a biological contaminant or pathogen that is capable of causing a deleterious effect, either alone or in combination with another factor, such as a second biological contaminant or pathogen or a native protein (wild-type or mutant) or antibody, in a imal.
  • active biological contaminant or patnogen is mic ⁇ ucu ⁇ un- ut biological contaminants or pathogens that can adopt or may be present in a dormant state, such as spores or the like, but are capable of causing a deleterious effect either in that state or in another state.
  • active biological contaminant or pathogen is Bacillus anthracis, which is often employed as a weapon of bio-terrorism in the form of spores.
  • active biological contaminant or pathogen is also intended to include the products of certain biological contaminants or pathogens that are capable of causing a deleterious effect, either alone or in combination with another factor, in a mammal.
  • An example such a product is botulism toxin, which is produced by Clostridium botulinum.
  • stabilizer is intended to mean a compound or substance that, alone and/or in combination, reduces damage to the material being irradiated to an acceptable level.
  • Illustrative examples of stabilizers that are suitable for such use include, but are not limited to, the following, including structural analogs and derivatives thereof: antioxidants; free radical scavengers, including spin traps, such as tert-butyl- nitrosobutane (tNB), a-phenyl-tert-butylnitrone (PBN), 5,5-dimethylpyrroline-N-oxide (DMPO), tert-butylnitrosobenzene (BNB), alpha-(4-pyridyl-l-oxide)-N-tert-butylnitrone (4-POBN) and 3,5-dibromo-4-nitroso-benzenesulphonic acid (DBNBS); combination stabilizers, i.e., stabilizers which are effective at quenching
  • stabilizers include, but are not limited to, the following: fatty acids, including 6,8-dimercapto-octanoic acid (lipoic acid) and its derivatives and analogues (alpha, beta, dihydro, bisno and tetranor lipoic acid), thioctic acid, 6,8- dimercapto-octanoic acid, dihydrolopoate (DL-6,8-dithioloctanoic acid methyl ester), lipoamide, bisonor methyl ester and tetranor-dihydrolipoic acid, omega-3 fatty acids, omega-6 fatty acids, omega-9 fatty acids, furan fatty acids, oleic, linoleic, linolenic, arachidonic, eicosapentaenoic (EPA), docosahexaenoic (DHA), and palmitic acids and their salts and derivatives; carotenes, including alpha-, beta-
  • Particularly preferred examples include single stabilizers or combinations of stabilizers that are effective at quenching both Type I and Type II photodynamic reactions, and volatile stabilizers, which can be applied as a gas and/or easily removed by evaporation, low pressure, and similar methods.
  • moisture content is intended to mean the amount or proportion of water in a particular atmosphere, such as that within a container.
  • the moisture contents referenced herein refer to levels determined by the FDA approved, modified Karl Fischer method (Meyer and Boyd, Analytical Chem., 31:215-219, 1959; May, et al., J. Biol. Standardization, 10:249-259, 1982; Centers for Biologies Evaluation and Research, FDA, Docket No. 89D-0140, 83-93; 1990) or by near infrared spectroscopy.
  • the term "sensitizer” is intended to mean a substance that selectively targets viruses, bacteria (including inter- and mtracellular bacteria, such as mycoplasmas, ureaplasmas, nanobacteria, chlamydia, rickettsias), yeasts, molds, fungi, single or multi-cellular parasites, and/or prions or similar agents responsible, alone or in combination, for TSEs, rendering them more sensitive to inactivation by radiation, therefore permitting the use of a lower rate or dose of radiation and/or a shorter time of irradiation than in the absence of the sensitizer.
  • sensitizers include, but are not limited to, the following: psoralen and its derivatives and analogs (including 3-carboethoxy psoralens); inactines and their derivatives and analogs; angelicins, khellins and coumarins which
  • t ⁇ contain a halogen substituent and a water solubilization moiety, such as quaternary ammonium ion or phosphonium ion; nucleic acid binding compounds; brominated hematoporphyrin; phthalocyanines; purpurins; porphyrins; halogenated or metal atom- substituted derivatives of dihematoporphyrin esters, hematoporphyrin derivatives, benzoporphyrinderivatives,hydrodibenzopo ⁇ hyrin dimaleimade, hydrodibenzopo ⁇ hyrin, dicyano disulfone, tetracarbethoxy hydrodibenzoporphyrin, and tetracarbethoxy hydrodibenzoporphyrin dipropionamide; doxorubicin and daunomycin, which may be modified with halogens or metal atoms; netropsin; BD peptide, S2 peptide; S-
  • atoms which bind to prions, and thereby increase their sensitivity to inactivation by radiation may also be used.
  • An illustrative example of such an atom would be the Copper ion, which binds to the prion protein and, with a Z number higher than the other atoms in the protein, increases the probability that the prion protein will absorb energy during irradiation, particularly gamma irradiation.
  • the term "radiation" is intended to mean radiation of sufficient energy to reduce the level of at least one active biological contaminant or pathogen that may be present in or on a material.
  • Types of radiation include, but are not limited to, the following: (i) corpuscular (streams of subatomic particles such as neutrons, electrons, and/or protons); (ii) electromagnetic (originating in a varying electromagnetic field, such as radio waves, visible (both mono and polychromatic) and invisible light, infrared, ultraviolet radiation, x-radiation, and gamma rays and mixtures thereof); and (iii) sound and pressure waves.
  • Such radiation is often described as either ionizing (capable of producing ions in irradiated materials) radiation, such as gamma rays, and non-ionizing radiation, such as visible light.
  • the sources of such radiation may vary and, in general, the selection of a specific source of radiation is not critical provided that sufficient radiation is given in an appropriate time and at an appropriate rate to effect sterilization.
  • gamma radiation is usually produced by isotopes of Cobalt or Cesium, while UN and X-rays are produced by machines that emit UV and X-radiation, respectively, and electrons are often used to sterilize materials in a method known as "E-beam" irradiation that involves their production via a machine. Visible light, both mono- and polychromatic, is produced by
  • tl machines may, in practice, be combined with invisible light, such as infrared and UN, that is produced by the same machine or a different machine.
  • invisible light such as infrared and UN
  • the term "to protect” is intended to mean to reduce any damage to the material being irradiated, which would otherwise result from the irradiation of that material, to a level that is acceptable.
  • a substance or process "protects” a material from radiation if the presence of that substance or carrying out that process results in less damage to the material from irradiation than in the absence of that substance or process.
  • an "acceptable level” of damage may vary depending upon certain features of the particular method(s) of the present invention being employed, such as the nature and characteristics of the particular material being irradiated, and can be determined empirically by one skilled in the art. An "unacceptable level” of damage would therefore be a level of damage that would preclude the intended use of the material being irradiated. The particular level of damage in a given material may be determined using any of the methods and techniques known to one skilled in the art.
  • unacceptable levels of damage include the following: paper that becomes brittle; discoloration of paper and/or inks; fading of inks; fading or discoloration of transparent windows for address(es); and stiffening of paper.
  • D 10 dose is intended to mean the dose of radiation necessary to reduce the level of at least one active biological contaminant or pathogen to 10% of its pre-irradiation level.
  • a first embodiment of the present invention is directed to a method for combating bio-terrorism involving the presence of active biological contaminants or pathogens in or on a material, said method comprising irradiating said material with radiation for a time and at a rate effective to reduce the level of active biological contaminants or pathogens in or on said material.
  • a second embodiment of the present invention is directed to a method for combating bio-terrorism involving the presence of active biological contaminants or pathogens in or on a material, said method comprising: (i) performing at least one stabilizing process on said material, said stabilizing process selected from the group consisting of: (a) applying to said material at least one stabilizer in an amount effective to protect said material from said radiation; (b) placing said material in a container and reducing the moisture content of the atmosphere inside said container to a level effective to protect said material from said radiation; (c) reducing the temperature of said material to a level effective to protect said material from said radiation; (d) placing said material in a container and reducing the oxygen content of the atmosphere inside said container to a level effective to protect said material from said radiation; and (e) applying to said material at least one solvent in an amount effective to protect said material from said radiation; and (ii) radiating said material with a suitable radiation for a time and at a rate effective to reduce the level of active biological contaminants or pathogens in or on said material.
  • a third embodiment of the present invention is directed to a method for combating bio-te ⁇ orism involving the presence of active biological contaminants or pathogens in or on material, said method comprising: (i) performing at least two stabilizing process on said material, said stabilizing processes selected from the group consisting of: (a) applying to said material at least one stabilizer; (b) placing said material in a container and reducing the moisture content of the atmosphere inside said container; (c) reducing the temperature of said material; (d) placing said material in a container and reducing the oxygen content of the atmosphere inside said container; and (e) applying to said material at least one solvent; and (ii) i ⁇ adiating said material with a suitable radiation for a time and at a rate effective to reduce the level of active biological contaminants or pathogens in or on said material, wherein said at least two stabilizing processes are together effective to protect said material from said radiation and further wherein said at least two stabilizing processes may be performed in any order.
  • the particular geometry of the material being irradiated may be determined empirically by one skilled in the art.
  • a preferred embodiment is a geometry that provides for an even rate of i ⁇ adiation throughout the material.
  • a particularly prefe ⁇ ed embodiment is a geometry that results in a short path length for the radiation through the material, thus minimizing the differences in radiation dose between the front and back of the material or at its edges and center, if it or the radiation source is rotated. This may be further minimized in some preferred geometries, particularly those wherein the material has a constant radius about its axis that is perpendicular to the radiation source, by the utilization of a means of rotating the preparation about said axis.
  • a stabilizer or mixture of stabilizers, is applied to the material prior to irradiation thereof with radiation. This stabilizer is preferably applied to the material in an amount that is effective to protect the material from the radiation.
  • Suitable amounts of stabilizer may vary depending upon certain features of the particular method(s) of the present invention being employed, such as the particular stabilizer being used and/or the nature and characteristics of the material being irradiated, and can be determined empirically by one skilled in the art.
  • the material to be irradiated is placed within an effective container prior to irradiation.
  • An "effective container” for containing a material during irradiation is one that is stable under the influence of irradiation, minimizes the interactions between the radiation and the material and isolates the material from the external environment.
  • the term "container” includes a facility, such as a sealed room, provided that it sufficiently isolates the material from the external environment.
  • Preferred containers both maintain an effective seal against the external environment pre-, during and post-i ⁇ adiation, and are not reactive with the material within, nor do they produce chemicals that may interact with the material within.
  • Other preferred containers include means for modifying the atmosphere inside the container which maintaining an effective seal against the external environment.
  • Illustrative examples include, but are not limited to, containers that comprise glasses stable when i ⁇ adiated, stoppered with stoppers made of rubber that is relatively stable during radiation and liberates a minimal amount of compounds from within, and sealed with metal crimp seals of aluminum or other suitable materials with relatively low Z numbers.
  • Suitable containers can be determined by measuring their physical performance, and the amount and type of reactive leachable compounds post-i ⁇ adiation and by examining other characteristics known to be important to the containment of materials empirically by one skilled in the art.
  • the moisture content of the atmosphere inside the container may be reduced prior to irradiation of the material with radiation.
  • the moisture content of the atmosphere inside the container is preferably reduced to a level that is
  • Suitable levels of moisture content may vary depending upon certain features of the particular method(s) of the present invention being employed, such as the nature and characteristics of the particular material being i ⁇ adiated and/or its intended use, and can be determined empirically by one skilled in the art. There may be materials for which it is desirable to maintain the moisture content of the atmosphere inside the container to within a particular range, rather than a specific value.
  • the moisture content of the material itself may be reduced prior to i ⁇ adiation of the material with radiation.
  • the moisture content of the material is preferably reduced to a level that is effective to protect the material from the radiation.
  • Suitable levels of moisture content may vary depending upon certain features of the particular method(s) of the present invention being employed, such as the nature and characteristics of the particular material being i ⁇ adiated and/or its intended use, and can be determined empirically by one skilled in the art. There may be materials for which it is desirable to maintain the moisture content to within a particular range, rather than a specific value.
  • the moisture content of the atmosphere inside the container and/or the material may be less than 80%, 60%, 40% or 20%, generally less than about 15%, typically less than about 10%, more typically less than about 9%, even more typically less than about 8%, usually less than about 5%, preferably less than about 3.0%, more preferably less than about 2.0%, even more preferably less than about 1.0%, still more preferably less than about 0.5%, still even more preferably less than about 0.2% and most preferably less than about 0.08%.
  • the moisture content for a particular atmosphere and/or material may be found to lie within a range, rather than at a specific point.
  • a range for the prefe ⁇ ed moisture content may be determined empirically by one skilled in the art.
  • the reduction in moisture content may reduces the number of targets for free radical generation. Similar results might therefore be achieved by lowering the temperature of the material. These results may permit the use of a higher rate and/or dose of radiation than might otherwise be acceptable.
  • the methods described herein may be performed at any temperature that doesn't result in unacceptable damage to the material, i.e., damage that would preclude the intended use of the material.
  • IS methods described herein are performed at ambient temperature or below ambient temperature.
  • the moisture content may be reduced by any of the methods and techniques known to those skilled in the art for reducing moisture in an atmosphere or a material without producing an unacceptable level of damage.
  • prefe ⁇ ed examples of such methods include, but are not limited to, applying heat and/or reduced pressure to the atmosphere inside the container, introducing at least one hygroscopic material into the container and introducing dry gas into the atmosphere inside the container.
  • preferred examples of such methods include, but are not limited to, lyophilization, evaporation, concentration, centrifugal concentration, vitrification, spray- drying, distillation, freeze-distillation and partitioning during and/or following lyophilization.
  • the radiation employed in the methods of the present invention may be any radiation effective for reducing the level of one or more active biological contaminants or pathogens.
  • the radiation may be co ⁇ uscular, including E-beam radiation.
  • the radiation is electromagnetic radiation, including x-rays, infrared, visible light, UV light and mixtures of various wavelengths of electromagnetic radiation.
  • a particularly prefe ⁇ ed form of radiation is gamma radiation.
  • the material is i ⁇ adiated with the radiation at a rate effective for reducing the level of one or more active biological contaminants or pathogens, while not producing an unacceptable level of damage to the material being irradiated.
  • Suitable rates of i ⁇ adiation may vary depending upon certain features of the methods of the present invention being employed, such as the nature and characteristics of the particular material being i ⁇ adiated, the particular form of radiation involved and/or the particular biological contaminants or pathogens being inactivated. Suitable rates of i ⁇ adiation can be determined empirically by one skilled in the art. Preferably, the rate of i ⁇ adiation is constant for the duration of the sterilization procedure. When this is impractical or otherwise not desired, a variable or discontinuous irradiation may be utilized.
  • the rate of irradiation may be optimized to produce the most advantageous combination of protection to the material and time required to complete the operation. Both low ( ⁇ 3 kGy/hour) and high (>3 kGy/hour) rates may be utilized in the methods described herein to achieve such results.
  • the rate of irradiation is preferably be selected to optimize the protection of the material while still reducing the level of one or more active biological contaminants or pathogens.
  • reducing the rate of i ⁇ adiation may serve to decrease damage to the material, it will also result in longer i ⁇ adiation times being required to achieve a particular desired total dose.
  • a higher dose rate may therefore be preferred in certain circumstances, such as to minimize logistical issues and costs, and may be possible when used in accordance with the methods described herein for protecting a material from i ⁇ adiation.
  • the "rate" of i ⁇ adiation means the total dose of radiation over the total time of i ⁇ adiation, or may be based on the total dose received from the time of first exposure to the time of last exposure or the total dose received during the time the machine is actually producing radiation.
  • the rate of irradiation is not more than about 3.0 kGy/hour, more preferably between about 0.1 kGy/hr and 3.0 kGy/hr, even more preferably between about 0.25 kGy/hr and 2.0 kGy/hour, still even more preferably between about 0.5 kGy/hr and 1.5 kGy/hr and most preferably between about 0.5 kGy/hr and 1.0 kGy/hr.
  • the rate of i ⁇ adiation is at least about 3.0 kGy/hr, more preferably at least about 6 kGy/hr, even more preferably at least about 16 kGy/hr, and even more preferably at least about 30 kGy/hr and most preferably at least about 45 kGy/hr or greater.
  • the rate of i ⁇ adiation is preferably at least in the range of 10,000 to 100,000 kGy/hr and more preferably at least about 1,000,000 kGy/hr.
  • the material being i ⁇ adiated is irradiated with the radiation for a time effective for reducing the level of one or more active biological contaminants or pathogens that may be present in or on the material.
  • the appropriate i ⁇ adiation time results in the appropriate dose of i ⁇ adiation being applied to the material to achieve such a result.
  • Suitable irradiation times may vary depending upon the particular form and rate of radiation involved and/or the nature and characteristics of the particular material being i ⁇ adiated.
  • Suitable i ⁇ adiation times can be determined empirically by one skilled in the art.
  • the material being i ⁇ adiated is irradiated with radiation up to a total dose effective for reducing the level of one or more active biological contaminants or pathogens that may be present in or on the material, while not producing an unacceptable level of damage to that material.
  • Suitable total doses of radiation may vary depending upon certain features of the methods of the present invention being employed, such as the nature and characteristics of the particular material being i ⁇ adiated, the particular form of radiation involved and or the particular biological contaminants or pathogens that may be present. Suitable total doses of radiation can be determined empirically by one skilled in the art.
  • the total dose of radiation is at least 25 kGy, more preferably at least 45 kGy, even more preferably at least 75 kGy, and still more preferably at least 100 kGy or greater, such as 150 kGy or 200 kGy or greater.
  • an effective amount of at least one sensitizing compound may optionally be applied to the material prior to i ⁇ adiation, for example to enhance the effect of the i ⁇ adiation on the biological contaminant(s) or pathogen(s) that may be present therein, while employing the methods described herein to minimize the deleterious effects of irradiation upon the material.
  • Suitable sensitizers are known to those skilled in the art, and include psoralens and their derivatives and inactines and their derivatives.
  • the i ⁇ adiation of the material may occur at any temperature that is not deleterious to the material being i ⁇ adiated.
  • the material is i ⁇ adiated at ambient temperature.
  • the material is i ⁇ adiated at reduced temperature, i.e. a temperature below ambient temperature or lower, such as 0°C, -20°C, - 40°C, -60°C, -78°C or even -196°C.
  • the material is i ⁇ adiated at elevated temperature, i.e. a temperature above ambient temperature or higher, such as 37°C, 60°C, 72°C or 80°C.
  • the use of elevated temperature may enhance the effect of irradiation on the biological contaminant(s) or pathogen(s) that may be present in or on the material and therefore allow the use of a lower total dose of radiation.
  • the irradiation of the material occurs at a temperature that protects the material from radiation. Suitable temperatures can be determined empirically by one skilled in the art.
  • the temperature at which irradiation is performed may be found to lie within a range, rather than at a specific point. Such a range for the preferred temperature for the i ⁇ adiation of a particular material may be determined empirically by one skilled in the art. According to another prefe ⁇ ed embodiment, the material to be irradiated may be shielded from radiation other than that desired in order to minimize the deleterious effects upon the material and/or any added stabilizer(s) by undesired radiation.
  • the irradiation of the material may occur at any pressure which is not deleterious to the material being i ⁇ adiated.
  • the material is i ⁇ adiated at elevated pressure. More preferably, the material is irradiated at elevated pressure due to the application of sound waves or the use of a gas or volatile solvent. While not wishing to be bound by any theory, the use of elevated pressure may enhance the effect of irradiation on the biological contaminant(s) or pathogen(s) that may be present in or on the material and/or enhance the protection afforded by one or more stabilizers, and therefore allow the use of a lower total dose of radiation. Suitable pressures can be determined empirically by one skilled in the art.
  • the i ⁇ adiation of the material may occur under any atmosphere that is not deleterious to the material being treated.
  • the material is held in a low oxygen atmosphere or an inert atmosphere.
  • the atmosphere is preferably composed of a noble gas, such as helium or argon, more preferably a higher molecular weight noble gas, and most preferably argon.
  • the material is held under vacuum while being irradiated.
  • a material is stored under vacuum or an inert atmosphere (preferably a noble gas, such as helium or argon, more preferably a higher molecular weight noble gas, and most preferably argon) prior to i ⁇ adiation.
  • a material is held under low pressure, to decrease the amount of gas, particularly oxygen, prior to irradiation, either with or without a prior step of reducing the moisture content.
  • the amount thereof these may be reduced by any of the methods and techniques known and available to those skilled in the art, such as the controlled reduction of pressure within the container (rigid or flexible) holding the material to be i ⁇ adiated or by introducing an inert gas, such as a noble gas (e.g. helium or argon).
  • an inert gas such as a noble gas (e.g. helium or argon).
  • a stabilizer is applied to the material according to any of the methods and techniques known and available to one skilled in the art, including soaking the material in a solution containing the stabilizer, preferably under pressure, at elevated temperature and/or in the presence of a penetration enhancer, such as dimethylsulfoxide.
  • a penetration enhancer such as dimethylsulfoxide.
  • Other methods of introducing the stabilizer(s) include, but are not limited to, applying a gas containing the stabilizer(s), preferably under pressure and/or at elevated temperature, placing the material under reduced pressure and then introducing a gas or solution containing the stabilizer(s), and combinations of two or more of these methods.
  • One or more sensitizers may also be introduced into a tissue according to such methods.
  • a particular material may also be held at a reduced temperature and kept under vacuum prior to irradiation to further minimize undesirable effects.
  • the material to be i ⁇ adiated is examined with a suitable detection technique, such as the use of X-rays or "sniffers".
  • a suitable detection technique such as the use of X-rays or "sniffers”.
  • Such screening can, for example, ensure that no radiodense substance is present in or on the material that might reduce the effectiveness of the methods of the present invention. Any such materials should be destroyed or, in the alternative, the conditions of i ⁇ adiation may be varied so that the methods of the present invention are effective at reducing the level of at least active biological contaminant or pathogen in or on the material.
  • screening can be employed to determine the level of active biological contaminants or pathogens.
  • the conditions of irradiation may be varied so that the methods of the present invention are effective at reducing the level of at least active biological contaminant or pathogen in or on the material.
  • Screening can also be used to identify suspect materials, i.e. materials which may have in or on them an active biological contaminant or pathogen, through characteristics such as excess postage, foreign postmarks, suspicious packaging or misspellings and inco ⁇ ect or unknown return addresses.
  • the materials that can be i ⁇ adiated to reduce the level of at least one active biological contaminant or pathogen include, but are not limited to, letters and/or packages delivered through conventional mail or delivery services and cu ⁇ ency.
  • letters or packages or cu ⁇ ency are contained within a material, such as an envelope or the like, that is resistant to the effects of radiation, particularly gamma radiation.
  • a material such as an envelope or the like, that is resistant to the effects of radiation, particularly gamma radiation.
  • Such materials are known to those skilled in the art.
  • the pu ⁇ ose of this experiment was to determine the effects of gamma i ⁇ adiation on various paper samples such as stationery, envelopes, packages, and binding tape that might be sent through the postal system.
  • Background Various paper samples (paper, envelopes, packages, adhesive tapes, etc.) were gathered together and placed in a container for irradiation.
  • the various samples received modifications with laser jet printing, irikjet printing, ballpoint printing, tape, packaging tape, wettable stamps, and adhesive stamps as appropriate. All adhesives were applied or sealed using pressure or water to wet the adhesive.
  • Samples gamma i ⁇ adiated at ambient temperature and atmosphere were i ⁇ adiated at dose rates of 6.42 - 6.68 kGy/hr to total doses of 46.3 kGy - 50.0 kGy.
  • Samples gamma i ⁇ adiated on dry ice were irradiated at dose rates of 1.43-1.54 kGy/hr to total doses of 46.3-50.0 kGy.
  • the containers were opened.
  • the containers containing DTT were evaluated for odor by sniffing the container and pieces of paper for odor permeance.
  • the corresponding paper samples from each of the 6 groups were pooled and compared in a blinded manner by three people. Any changes in appearance such as color change of the paper, inks, and adhesives were noted. Adhesive function was evaluated manually. Any gross differences in the physical properties of the papers such as brittleness or changes in texture were also noted. Observations are set forth in Tables 1 and 2.
  • the papers were stored in a cardbox with little exposure to light for one year. The papers were then re-examined by three people (the 3 who viewed them at time zero) in a blinded manner to determine if there were any changes upon long-term storage.
  • the 100 kGy samples first received a dose of 50 kGy at a dose rate of 4.45 kGy/hr. All groups were then gamma irradiated at ambient or dry ice temperatures at a rate of approx. 2.2 kGy/hr to a total of 50 kGy. Evaluation Procedures:
  • the containers were opened.
  • the containers containing DTT were evaluated for odor by sniffing the container and pieces of paper for odor permeance.

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  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract

L'invention concerne des procédés permettant de lutter contre le bioterrorisme, plus particulièrement des procédés permettant de lutter contre le bioterrorisme par irradiation d'un matériau, tel qu'une lettre, un paquet ou un papier-monnaie, afin de réduire le niveau d'un ou de plusieurs contaminants biologiques ou agents pathogènes biologiques pouvant se trouver sur ou dans le matériau, tels que des virus, des bactéries (y compris les bactéries inter et intracellulaires, telles que les mycoplasmes, les uréaplasmes, les nanobactéries, les chlamydia, et les rickettsies), des levures, des moisissures, des champignons, des parasites mono ou multicellulaires, et/ou des prions ou des agents similaires responsables, seuls ou en combinaison d'encéphalopathies spongiformes transmissibles.
PCT/US2002/031584 2001-10-19 2002-10-21 Procedes de lutte contre le bioterrorisme WO2003035238A2 (fr)

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AU2002356540A AU2002356540A1 (en) 2001-10-19 2002-10-21 Methods for combating bio-terrorism

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8480852B2 (en) 2009-11-20 2013-07-09 Kimberly-Clark Worldwide, Inc. Cooling substrates with hydrophilic containment layer and method of making
US8795717B2 (en) 2009-11-20 2014-08-05 Kimberly-Clark Worldwide, Inc. Tissue products including a temperature change composition containing phase change components within a non-interfering molecular scaffold
US9181465B2 (en) 2009-11-20 2015-11-10 Kimberly-Clark Worldwide, Inc. Temperature change compositions and tissue products providing a cooling sensation

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WO2000028552A1 (fr) * 1998-11-09 2000-05-18 Clean Earth Technologies, Llc Procede et appareil de decontamination aux ultraviolets de surfaces et de nuages d'aerosols photosensibilises

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US5712086A (en) * 1990-05-15 1998-01-27 New York Blood Center, Inc. Process for transfusing cell containing fractions sterilized with radiation and a quencher of type I and type II photodynamic reactions
WO2000028552A1 (fr) * 1998-11-09 2000-05-18 Clean Earth Technologies, Llc Procede et appareil de decontamination aux ultraviolets de surfaces et de nuages d'aerosols photosensibilises

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8480852B2 (en) 2009-11-20 2013-07-09 Kimberly-Clark Worldwide, Inc. Cooling substrates with hydrophilic containment layer and method of making
US8795717B2 (en) 2009-11-20 2014-08-05 Kimberly-Clark Worldwide, Inc. Tissue products including a temperature change composition containing phase change components within a non-interfering molecular scaffold
US8894814B2 (en) 2009-11-20 2014-11-25 Kimberly-Clark Worldwide, Inc. Cooling substrates with hydrophilic containment layer and method of making
US9181465B2 (en) 2009-11-20 2015-11-10 Kimberly-Clark Worldwide, Inc. Temperature change compositions and tissue products providing a cooling sensation
US9545365B2 (en) 2009-11-20 2017-01-17 Kimberly-Clark Worldwide, Inc. Temperature change compositions and tissue products providing a cooling sensation

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