US20050032913A1 - Decontamination of prion-contaminated surfaces with phenols - Google Patents

Decontamination of prion-contaminated surfaces with phenols Download PDF

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US20050032913A1
US20050032913A1 US10/637,149 US63714903A US2005032913A1 US 20050032913 A1 US20050032913 A1 US 20050032913A1 US 63714903 A US63714903 A US 63714903A US 2005032913 A1 US2005032913 A1 US 2005032913A1
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Prior art keywords
phenol
composition
prions
log
acid
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Abandoned
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US10/637,149
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Gerald McDonnell
Herbert Kaiser
Kathleen Antloga
Shahin Keller
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American Sterilizer Co
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Steris Inc
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Priority to US10/637,149 priority Critical patent/US20050032913A1/en
Assigned to STERIS INC. reassignment STERIS INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ANTLOGA, KATHLEEN M., KAISER, HERBERT J., KELLER, SHAHIN, MCDONNELL, GERALD E.
Priority to PCT/US2004/024801 priority patent/WO2005018686A2/en
Priority to ES04786440T priority patent/ES2319772T3/es
Priority to CA2533729A priority patent/CA2533729C/en
Priority to EP04786440A priority patent/EP1658102B1/en
Priority to JP2006522648A priority patent/JP4993643B2/ja
Priority to TW093123052A priority patent/TW200524645A/zh
Priority to DE602004018511T priority patent/DE602004018511D1/de
Priority to KR1020067002736A priority patent/KR20060060681A/ko
Priority to CNA2004800227382A priority patent/CN1832764A/zh
Priority to AT04786440T priority patent/ATE417631T1/de
Priority to AU2004266577A priority patent/AU2004266577B2/en
Publication of US20050032913A1 publication Critical patent/US20050032913A1/en
Assigned to STERIS INC. reassignment STERIS INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ANTLOGA, KATHLEEN M., MCDONNELL, GERALD E., KAISER, HERBERT J., KELLER, SHAHIN (NMI)
Assigned to AMERICAN STERILIZER COMPANY reassignment AMERICAN STERILIZER COMPANY ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: STERIS INC.
Priority to JP2010029543A priority patent/JP2010131430A/ja
Priority to US12/711,446 priority patent/US8236492B2/en
Abandoned legal-status Critical Current

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2/00Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • A61L2/18Liquid substances or solutions comprising solids or dissolved gases
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2/00Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2/00Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • A61L2/22Phase substances, e.g. smokes, aerosols or sprayed or atomised substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2/00Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • A61L2/23Solid substances, e.g. granules, powders, blocks, tablets

Definitions

  • the present invention relates to the field of biological decontamination.
  • the invention finds particular application in connection with the removal and/or destruction of harmful biological materials, such as prions (proteinaceous-infectious agents), from medical, dental, and pharmaceutical instruments and will be described with particular reference thereto. It will be appreciated, however, that the method and system of the present invention may be utilized in biological decontamination of a wide range of equipment, instruments, and other surfaces contaminated with prion infected material, such as pharmaceutical preparation facilities, food processing facilities, laboratory animal research facilities including floors, work surfaces, equipment, cages, fermentation tanks, fluid lines, and the like.
  • TSEs transmissible spongiform encephalopathies
  • CJD Creutzfeldt-Jakob disease
  • vCJD variant CJD
  • BSE Bovine Spongiform Encephalopathy
  • All of these diseases attack the neurological organs of the animal or animals which are susceptible to the particular disease. They are characterized by initially long incubation times followed by a short period of neurological symptoms, including dementia and loss of coordination, and eventually death.
  • the infectious agent responsible for these diseases is thought to be a simple protein, with no associated nucleic acids.
  • the pathogenic mechanism for such prion diseases is proposed to involve an initially normal host encoded protein.
  • the protein undergoes a conformational change to an abnormal form (a prion), which has the ability of self-propagation.
  • the exact cause of this change is, at present, unknown.
  • the abnormal form of the protein is not broken down effectively in the body and its accumulation in certain tissues (in particular neural tissue) eventually causes tissue damage, such as cell death. Once significant neural tissue damage has occurred, the clinical signs are observed.
  • Prion diseases may thus be classified as protein aggregation diseases, which also include several other fatal diseases, such as Alzheimer's disease and amyloidosis.
  • CJD the most prevalent prion disease in humans (occurring in roughly 1:1,000,000 of the population), about 85% of cases are thought to arise sporadically, about 10% are thought to be inherited, and about 5% arise iatrogenically.
  • prion diseases can be transmitted by certain high-risk tissues, including the brain, spinal cord, cerebral spinal fluids, and the eye. Iatrogenic transmission has been reported during several procedures, including dura-mater grafting, corneal transplants, pericardial homografts, and through human gonadotropin and human growth hormone contamination. Transmission via medical devices has also been reported, including from neurosurgical instruments, depth electrodes, and other devices used for surgical procedures in close proximity to the central nervous system. Concerns are being raised that procedures previously considered to be “low risk” in terms of prion infection, such as tonsillectomy and dental procedures, may pose unacceptable risks of infection, particularly, if the incidence of prion-related diseases increases.
  • prion containing residue may remain on the surgical instruments, particularly neurosurgical and ophthalmological instruments. During the long incubation period, it is extremely difficult to determine whether a surgical candidate is a prion carrier.
  • sanitizing connotes free from dirt or germs by cleaning.
  • Disinfecting calls for cleansing in order to destroy harmful microorganisms.
  • Sterilization the highest level of biological contamination control, connotes the destruction of all living microorganisms.
  • Prions are notoriously very hardy and demonstrate resistance to routine methods of decontamination and sterilization. Unlike microorganisms, prions have no DNA or RNA to destroy or disrupt. Prions, due to their hydrophobic nature, tend to aggregate together in insoluble clumps. Under many conditions that lead to successful sterilization of microorganisms, prions form tighter clumps, which protect themselves and underlying prions from the sterilization process.
  • the present invention provides a new and improved method of treatment of surfaces contaminated with prion-infected material, which overcomes the above-referenced problems and others.
  • a method of treating a body which is contaminated with prions includes contacting the body with a composition comprising a phenol to inactivate prions on the body.
  • a method of determining the effectiveness of a phenol-based decontaminant composition on a material which is contaminated with prions includes combining a solution of the phenol-based decontaminant with a protein material, determining a measure of the phenol taken up by the material, and determining the effectiveness of the composition based on the amount of phenol taken up.
  • One advantage of the present invention is that it is gentle on instruments.
  • Another advantage of the present invention is that it deactivates prions quickly and effectively.
  • Another advantage of the present invention is that it is compatible with a wide variety of materials and devices.
  • the invention may take form in various components and arrangements of components, and in various steps and arrangements of steps.
  • the drawings are only for purposes of illustrating a preferred embodiment and are not to be construed as limiting the invention.
  • FIG. 1 is a plot showing Log reduction prions vs. the partition coefficient for various phenols
  • FIG. 2 is a plot showing the correlation between partition coefficients obtained by different methods
  • FIG. 3 is a plot showing the effect of temperature on the reduction of prions by phenols
  • FIG. 4 is a plot showing the interactions of various phenols with BSA
  • FIG. 5 is a plot of the percentage of initial concentration absorbed vs the HPLC retention time of various phenols.
  • FIG. 6 is a plot of phenol equivalents absorbed vs Log P c for various phenols.
  • a disinfectant composition which is effective on a wide range of bodies, including surfaces and liquid bodies, for reduction or elimination of hazardous prions includes a phenol or combination of phenols.
  • Surfaces for which the composition is effective at removing or substantially reducing the prion contamination include surfaces of instruments employed in medical, dental, and pharmaceutical procedures, surfaces of equipment used in the food and beverage processing industry and work surfaces, walls, floors, ceilings, fermentation tanks, fluid supply lines, and other potentially contaminated surfaces in hospitals, industrial facilities, research laboratories, and the like.
  • Particular examples include the treatment of medical waste, such as blood, tissue and other body waste, prior to disposal, treatment of rooms, cages, and the like used for housing animals known or suspected to be infected with prions, decontamination of BSE infected areas, including slaughterhouses, food processing facilities, and the like, medical device reprocessing, decontamination of disinfection or sterilization systems, formulation of pharmaceuticals, medicaments, and cleaning agents having antifungal, antiviral, antituberculoidal, and antibacterial efficacy, as well as prion efficacy.
  • medical waste such as blood, tissue and other body waste
  • the composition includes one or more phenols.
  • Suitable phenols include alkyl, chloro, and nitro-substituted phenols and biphenols, and carboxylic acids thereof.
  • Exemplary phenols include, but are not limited to phenol; 2,3-dimethylphenol; 3,5-dimethoxyphenol (3,5 DiMeOphenol); 2,6-dimethoxyphenol (2,6 DiMeOphenol); o-phenylphenol (OPP); p-tertiary-amylphenol (PTAP); o-benzyl-p-chlorophenol (OBPCP); p-chloro, m-cresol (PCMC); o-cresol; p-cresol; 2,2-methylenebis(p-chlorophenol); 3,4-dihydroxybenzoic acid (3,4DiOH benzoic); p-hydroxybenzoic acid; caffeic acid; protocatechuic acid; p-nitrophenol; 3-phenolphenol; 2,3-dimethoxyphenol (2,3
  • P c is defined as the calculated octanol-water partition coefficient. Higher Log P c values indicate the substance is more hydrophobic.
  • Software available for determining P c values is available for example from Advanced Chemistry Development Software.
  • Preferably at least one of the phenols in the composition has a Log P c value of at least 2.5, more preferably, at least about 3, and up to about 6.0, as measured by the ACD software method. It has been found that the higher the Log P value (more hydrophobic) the more phenol is absorbed. Accordingly, lower phenol concentrations can be used when the phenol is hydrophobic to achieve the desired prion destruction.
  • One particularly preferred phenol having a Log P c value of 3.35 is PCMX.
  • the composition is preferably acidic, i.e., has a pH of neutral (pH 7), or below, more preferably, a pH of about 6, or above, most preferably, a pH of about 2.5.
  • the composition may include an organic or inorganic acid which is added to adjust the pH, such as hydrochloric acid, glycolic acid, phosphoric acid, or the like.
  • the composition may be alkaline, for example, a base is added to adjust the pH, such as sodium hydroxide, potassium hydroxide, or the like.
  • the alkalinity is such that no more than 50% of the phenol is ionized.
  • the composition includes water or other suitable solvent.
  • the composition is preferably provided as a concentrate, which is diluted in water to form a decontaminant solution of a suitable concentration for decontamination.
  • the concentrate is diluted to about a 1% by weight of the solution.
  • the concentrate can be used at higher concentrations, e.g., at about 5% by weight of the solution, or more. Unless otherwise specified, all concentrations are provided for the concentrate.
  • the total molar phenol concentration of the concentrate is about 0.1M-11.0M, or greater, more preferably, about 0.2M, or greater, and most preferably, about 0.5M, or greater.
  • Effective compositions which destroy at least 99% of harmful proteins (e.g., prions) have been formulated with total phenol concentrations of about 0.2M-0.5M, or greater.
  • composition may also include other ingredients, depending on the specific application. Suitable ingredients include sequestering agents for removing water hardness salts, cosolvents, surfactants, corrosion inhibitors, buffering agents, and the like.
  • the sequestering agent is preferably an organic acid, inorganic acid, or a mixture thereof.
  • Suitable organic acids include mono- and di-aliphatic carboxylic acids, hydroxy-containing organic acids, and mixtures thereof.
  • Exemplary sequestering agents include glycolic acid, salicylic acid, succinic acid, lactic acid, tartaric acid, sorbic acid, sulfamic acid, acetic acid, benzoic acid, capric acid, caproic acid, cyanuric acid, dihydroacetic acid, dimethylsulfamic acid, propionic acid, polyacrylic acid, 2-ethyl-hexanoic acid, formic acid, fumaric acid, 1-glutamic acid, isopropyl sulfamic acid, naphthenic acid, oxalic acid, valeric acid, benzene sulfonic acid, xylene sulfonic acid, citric acid, cresylic acid, dodecylbenzene s
  • the acid is preferably present at a concentration of about 2-25% of the concentrate composition, more preferably, about 5-20%, more preferably, about 15-20%.
  • Suitable cosolvents include polyols containing only carbon, hydrogen and oxygen atoms.
  • Exemplary polyols are C 2 to C 6 polyols, such as 1,2-propanediol, 1,2-butanediol, hexylene glycol, glycerol, sorbitol, mannitol, and glucose.
  • Higher glycols, polyglycols, polyoxides and glycol ethers are also contemplated as co-solvents.
  • alkyl ether alcohols such as methoxyethanol, methoxyethanol acetate, butyoxyethanol (butyl cellosolve), propylene glycol, polyethylene glycol, polypropylene glycol, diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, tripropylene glycol methyl ether, propylene glycol methyl ether, dipropylene glycol methyl ether, propylene glycol methyl ether acetate, dipropylene glycol methyl ether acetate, ethylene glycol n-butyl ether, 1,2-dimethoxyethane, 2-ethoxy ethanol, 2-ethoxy-ethylacetate, phenoxy ethanol, and ethylene glycol n-propyl ether. Combinations of co-solvents may be used.
  • the polyol is preferably present as a concentration of at least 10%, more preferably, at least 20% and can be up to 40%.
  • Suitable surfactants include, anionic, cationic, non-ionic, zwitterionic surfactants.
  • Anionic surfactants such as alkylaryl anionic surfactants are particularly preferred.
  • Exemplary surfactants include dodecylbenzene sulfonic acid and sodium 1-octane sulfonate, and combinations thereof.
  • anionic surfactants are sulfates, sulfonates, particularly C 14 -C 18 sulfonates, sulfonic acids, ethoxylates, sarcosinates, and sulfosuccinates such as sodium lauryl ether sulfate, triethanolamine lauryl sulfate, magnesium lauryl sulfate, sulfosuccinate esters, ammonium lauryl sulfate, alkyl sulfonates, sodium lauryl sulfate, sodium alpha olefin sulfonates, alkyl sulfates, sulfated alcohol ethoxylates, sulfated alkyl phenol ethoxylates, sodium xylene sulfonate, alkylbenzene sulfonates, triethanolamine dodecylbenzene sulfonate, sodium dodecylbenzene sulf
  • the composition may also include one or more soluble inorganic salts, such as sodium chloride.
  • Sodium chloride has been found to increase the effectiveness of certain phenols, particularly those which are not halogenated, such as OPP, while the effect on halogenated phenols, such as PCMX, is less marked.
  • An exemplary concentrate composition is as follows: Ingredient % by Weight of Composition Water Q.S., typically, about 35.0% Sequestering agent, e.g., Glycolic acid 0-25%, preferably, about 18.0 Surfactants, e.g., Dodecylbenzene 2-10%, preferably, about 7.0% Sulphonic acid Sodium C 14 -C 16 3-10%, preferably, about 6.0% Sulfonate Cosolvent, e.g., Hexylene Glycol 10-40%, preferably about 24.0% Phenols, e.g., OBPCOP 2-15%, preferably, about 9.0% OBPCOP 0.2-5%, preferably about 1.0%
  • Sequestering agent e.g., Glycolic acid 0-25%, preferably, about 18.0
  • Surfactants e.g., Dodecylbenzene 2-10%, preferably, about 7.0% Sulphonic acid Sodium C 14 -C 16 3-10%, preferably, about 6.
  • At least some of the OBPCOP or OBPCOP is replaced with a phenol which is more effective than either of these phenols, such as PCMX.
  • Such a composition has been shown to be effective against prion-contaminated surfaces when diluted to a concentration of 1% by weight of the concentrate in water. While the mechanism of inactivating prions is not fully understood, it is contemplated that the phenol may form a complex with the prion protein, rendering it harmless. The prion is then unable to replicate to produce further prions. Studies by the inventors suggest that the phenol generally does not break down the prion. It is proposed that a change in the three dimensional structure of the prion protein results from interactions with the phenol, inactivating the prion.
  • composition is compatible with a wide range of surfaces, as compared with conventional prion treatments, such as high temperatures or high concentrations of sodium hypochlorite or sodium hydroxide.
  • the composition may be applied in a variety of ways, including by spraying, coating, immersion, or the like.
  • the composition is applied in the form of a gel.
  • a thickening agent such as a natural or modified cellulose, is added to the formulation to increase the viscosity.
  • the composition may be applied at room temperature, although higher temperatures are preferred. It has been found that by heating the composition to at least 30° C., more preferably, around 40° C., or above, a substantial shortening in the time required for inactivation of prions is achieved.
  • a prion model e.g., a protein such as bovine serum albumin (BSA) may be used to evaluate formulations.
  • BSA bovine serum albumin
  • a preferred prion model is an ileal fluid dependant organism (IFDO).
  • IFDO's were identified by Burdon, et al. (Burdon, J. Med. Micro., 29: 145-157 (1989)) and described as being similar to prions in many respects, e.g., in resistance to disinfection and sterilization methods. Due to the ability to culture IFDO's artificially and detect them in the laboratory they provide a good model system for studying the effect of decontamination processes on prion inactivation.
  • the IFDOs are artificially cultured in a modified Mycoplasma base broth (Oxoid) and quantified by serial dilutions and plating on a similar agar.
  • the efficacy of the decontamination formulations is preferably studied by suspension testing at room temperature at about a 1% dilution of the concentrate composition in water, simulating use of the composition. Following suitable contact times, aliquots are sampled and quantified by serial dilution and plating into modified Mycoplasma agar.
  • the plates are preferably incubated at about 37° C. for several hours, preferably about 48 hours. The plates are examined and the number of colonies visible are counted.
  • Log reductions may then be determined (log reduction is a measure of the number of organisms removed expressed as the difference between the Log 10 of the initial number of organisms minus the Log 10 of the number of organisms after treatment. E.g., a 6 log reduction means that out of one million initial organisms a maximum of one remains after treatment).
  • BSA bovine serum albumin
  • solubility of the phenol in the composition has an effect on the degree to which the protein is complexed.
  • the lower the solubility of the phenol in the formulation the greater the degree of complexation—i.e., the more effective the phenol formulation is at prion inactivation.
  • Solubility is affected by the choice of phenol and the type and concentrations of other ingredients in the formulation, e.g., the solvents and cosolvents used.
  • compositions I-VII are listed in Table 1.
  • Composition I is a commercial formulation, LpHTM.
  • the IFDOs are artificially cultured in a modified Mycoplasma broth and quantified by serial dilutions and plating on a similar agar.
  • the efficacy of the compositions I-VII is studied by suspension testing at room temperature at a 1% dilution of the composition in water. Following a suitable contact time, e.g., 10 minutes, aliquots are sampled and quantified by serial dilution and plating into modified Mycoplasma agar. Following incubation at 37° C. for 48 hours, the plates are evaluated by counting visible colonies and log reductions are determined. Results with the compositions are compared with an existing phenolic product are shown in Table 1.
  • Formulation XIV with 2,4,5-Trichlorophenol achieved the greatest Log Reduction (4.9) better than the Log Reduction (4.0) achieved with LpH.
  • P c is defined as the calculated octanol-water partition coefficient.
  • the log P c values are calculated using two methods. The first method uses Alchemy 2000 Molecular Modeling Software (Tripos) along with a data set developed by STERIS Corporation. The second method uses Advanced Chemistry Development (ACD) Software Solaris v4.67 ( ⁇ 1994-2002 ACD). The calculated log P c values for each phenol are shown in TABLE 3: These values are compared with Log reduction colonies obtained in Example 2.
  • FIG. 1 shows the Log IFDO reduction vs Log P c (Alchemy 2000) and the Log P c (ACD) values.
  • the correlation between the Log P c (Alchemy 2000) and the Log P c (ACD) values is shown in FIG. 2 .
  • phenols having a log P c value between 2 and 6.5 display enhanced activity.
  • the phenols in the LpHTM product were found to be the most significant requirement for efficacy and were rated as OBPCP>>OPP>PTAP. When tested with equivocal concentrations of these phenols, the optimal combinations were shown to be formulation containing either OPBCP or OPP; PTAP was less effective.
  • the IFDO's are artificially cultured in a modified Mycoplasma broth and quantified by serial dilutions and plating on a similar agar.
  • the effect of temperature on phenol formulation activity is studied by suspension testing at a 1% dilution of the composition in water at various temperatures (20 and 40 ° C.) Following 5, 10, 15 and 20 minute contact times, aliquots are sampled and quantified by serial dilution and plating into modified Mycoplasma agar. After incubation at 37° C. for 48 hours, the plates are evaluated by counting visible colonies and log reductions are determined. Results comparing the phenol composition (LpH) at 20 and 40° C. are shown in FIG. 3 .
  • IFDO levels were reduced to below detectable levels (i.e., greater than 1 Log) in 5 minutes at 40° C., as compared to 15 minutes at 20° C.
  • Phenol solutions with different phenols were prepared as follows: about 1.38 grams of a mixture of a phenol with solubilizers, such as anionic surfactants, an organic acid, isopropyl alcohol, glycols, and an amine was dissolved in 99 mL of water to form a solution containing a total phenol concentration of 4 mM. About 1 g of BSA was added to the phenol solution to give a concentration of about 0.15 mM BSA (the molecular weight of BSA is presumed to be about 66,000 Daltons). The solution was stirred for 15 minutes and then centrifuged at 1800 rpm for five minutes. Aliquots were analyzed by high performance liquid chromatography (HPLC). FIG.
  • HPLC high performance liquid chromatography
  • Example 5 The percentages of initial concentration absorbed from Example 5 were plotted against the HPLC retention time of the phenol. FIG. 5 shows the correlation between these values. A correlation coefficient of 0.81 was obtained, suggesting that HPLC retention time is a fairly good predictor of the absorption of phenol by the protein.

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US10/637,149 2003-08-08 2003-08-08 Decontamination of prion-contaminated surfaces with phenols Abandoned US20050032913A1 (en)

Priority Applications (14)

Application Number Priority Date Filing Date Title
US10/637,149 US20050032913A1 (en) 2003-08-08 2003-08-08 Decontamination of prion-contaminated surfaces with phenols
AU2004266577A AU2004266577B2 (en) 2003-08-08 2004-08-02 Decontamination of prion-contaminated surfaces with phenols
KR1020067002736A KR20060060681A (ko) 2003-08-08 2004-08-02 프리온으로 오염된 표면의 페놀을 사용한 오염제거
AT04786440T ATE417631T1 (de) 2003-08-08 2004-08-02 Dekontamination von mit prionen verunreinigten oberflächen mit phenolen
CA2533729A CA2533729C (en) 2003-08-08 2004-08-02 Decontamination of prion-contaminated surfaces with phenols
EP04786440A EP1658102B1 (en) 2003-08-08 2004-08-02 Decontamination of prion-contaminated surfaces with phenols
JP2006522648A JP4993643B2 (ja) 2003-08-08 2004-08-02 フェノールを用いた、プリオンで汚染した表面の汚染除去
TW093123052A TW200524645A (en) 2003-08-08 2004-08-02 Decontamination of prion-contaminated surfaces with phenols
DE602004018511T DE602004018511D1 (de) 2003-08-08 2004-08-02 Dekontamination von mit prionen verunreinigten oberflächen mit phenolen
PCT/US2004/024801 WO2005018686A2 (en) 2003-08-08 2004-08-02 Decontamination of prion-contaminated surfaces with phenols
CNA2004800227382A CN1832764A (zh) 2003-08-08 2004-08-02 用酚类净化被朊病毒污染的表面
ES04786440T ES2319772T3 (es) 2003-08-08 2004-08-02 Descontaminacion con fenoles de superficies contaminadas con priones.
JP2010029543A JP2010131430A (ja) 2003-08-08 2010-02-12 フェノールを用いた、プリオンで汚染した表面の汚染除去
US12/711,446 US8236492B2 (en) 2003-08-08 2010-02-24 Decontamination of prion-contaminated surfaces with phenols

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US8653015B2 (en) * 2011-04-13 2014-02-18 American Sterilizer Company Environmentally friendly, multi-purpose refluxing cleaner
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CN107789647B (zh) * 2016-09-05 2021-02-02 上海赛伦生物技术股份有限公司 一种灭活动物血清或血浆中病毒的方法
CN108283631B (zh) * 2018-01-08 2021-03-30 南京中医药大学 一种肠道病毒的抑制剂及其应用

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US9604085B2 (en) 2008-01-22 2017-03-28 Emergent Protective Products Canada Ulc Method and formulation for neutralizing toxic chemicals and materials
US8653015B2 (en) * 2011-04-13 2014-02-18 American Sterilizer Company Environmentally friendly, multi-purpose refluxing cleaner
US10299473B2 (en) 2017-04-28 2019-05-28 American Sterilizer Company Low pH phenolic disinfectant without para tertiary amylphenol

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TW200524645A (en) 2005-08-01
AU2004266577A1 (en) 2005-03-03
JP2010131430A (ja) 2010-06-17
ATE417631T1 (de) 2009-01-15
CA2533729A1 (en) 2005-03-03
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WO2005018686A2 (en) 2005-03-03
KR20060060681A (ko) 2006-06-05
EP1658102B1 (en) 2008-12-17
JP4993643B2 (ja) 2012-08-08
JP2007501653A (ja) 2007-02-01
US8236492B2 (en) 2012-08-07
ES2319772T3 (es) 2009-05-12
CA2533729C (en) 2011-10-11
AU2004266577B2 (en) 2009-10-29

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