Chemical apparatus and process disinfecting – deodorizing – preser – Process disinfecting – preserving – deodorizing – or sterilizing – By sudden release of pressure
Reexamination Certificate
1998-10-02
2001-08-07
McKane, Elizabeth (Department: 1744)
Chemical apparatus and process disinfecting, deodorizing, preser
Process disinfecting, preserving, deodorizing, or sterilizing
By sudden release of pressure
C422S001000, C435S236000, C436S543000
Reexamination Certificate
active
06270723
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention relates to methods for sterilizing materials and preparing vaccines.
Various methods and devices exist for the sterilization, decontamination, or disinfection of biological and non-biological materials. These methods include thermal destruction (e.g., burning), heat sterilization, irradiation (e.g., ultraviolet or ionizing irradiation), gas sterilization (e.g., using ethylene oxide), photosensitization, membrane sterilization, or the use of chemical disinfectants (formaldehyde, glutaraldehyde, alcohols, mercury compounds, quaternary ammonium compounds, halogenated compounds, solvent/detergent systems, or peroxides).
Heat sterilization (e.g., autoclaving) is often used, for example, for sterilizing medical solutions prior to use in a patient. Heat sterilization typically requires heating a solution to 121° C. for a minimum of 15 minutes under pressure in an autoclave, maintaining the heat and pressure conditions for a period of time sufficient to kill bacteria, fungi, and protists and inactivate viruses in the solution.
Many reusable medical articles and materials are not suitable for disinfection or sterilization in an autoclave. For example, plastic parts on medical devices, hemodialyzers, and fiber optic devices are commonly sterilized by chemical germicide treatment. In general, germicides require several hours of treatment for the inactivation of microorganisms.
To ensure sterility in pharmaceutical production, gas sterilization is often employed. However, gas sterilization (e.g., using ethylene oxide) can be time-consuming, requiring prehumidification, heating, and evacuation of a sample chamber, followed by treatment with high concentrations of the gas for up to 20 hours at a time.
When properly used, traditional disinfectants can inactivate vegetative bacteria, certain fungi, and lipophilic or medium-sized viruses. However, these disinfectants often do not arrest tubercle bacillus, spore-forming bacteria, or non-lipophilic or small-sized viruses.
Another method for lysing cells, and thereby sterilizing a sample is described in Microbiology (Davis et al., Harper & Row, Hagerstown, Md., 1980). This procedure of freezing and thawing the sample is believed to exert its effect through formation of tiny pockets of ice within the cells when a suspension of bacteria is frozen. The ice crystals and the high localized concentrations of salts both cause damage to the bacteria. A single freezing event is generally sufficient to kill only some of the bacteria, but repeated freeze-thaw cycles result in a progressive decrease in viability. Lethality is correlated with slow freezing and rapid thawing.
Traditional freeze-thaw methods are limited in the speed of the freeze-thaw cycle by the time needed to transfer heat to and from the center of the sample to effect phase changes. The equilibrium rate is particularly slow in the case of large volume samples (e.g., about 100 ml or larger). Sterilization efficiency of the traditional methods is limited by the impracticality of performing a large number of freeze-thaw cycles by those methods.
Traditional methods of food preservation include pasteurization, in which a food is held at an elevated temperature for a period of time.
There is presently a need to develop methods for inactivating microbes and viruses from protein preparations while maintaining the integrity and therapeutic value of the proteins. The development of methods for inactivation of non-encapsulated viruses is especially challenging, since the outer coats of such viruses generally include proteins similar to the proteins one wishes to retain.
SUMMARY OF THE INVENTION
The invention is based on the discovery that biological and non-biological materials can be sterilized, decontaminated, or disinfected by repeatedly cycling between relatively high and low pressures. Pressure cycling can be carried out at low, ambient, or elevated temperatures (e.g., from about −40° C. to about 95° C.). New methods based on this discovery can have applications in, for example, the preparation of vaccines, the sterilization of blood plasma or serum, the decontamination of military devices, food and beverage production, and the disinfection of medical equipment. The new methods can also be incorporated into production processes or research procedures.
In general, the invention features a method for sterilizing a material. The method includes the steps of providing a material at an initial pressure (e.g., 1 atm) and temperature (e.g., 25° C., lower temperatures such as 0° C. or lower); increasing the pressure to an elevated pressure insufficient to irreversibly denature proteins (i.e., less than about 50,000 psi), but still high enough to kill at least some (e.g., at least 25%, 50%, 75%, 90%, 95%, 99%, or even substantially all) pathogens that contaminate the material (e.g., in the range of about 5,000 psi to about 50,000 psi, or in the range of about 10,000 psi to about 30,000 psi); and subsequently decreasing the pressure to the initial pressure or thereabouts, to provide a sterilized material.
The material can be chilled to a subzero temperature (e.g., from about −40° C. to about 0° C., especially between about −20° C. and about −5) either before or after the pressure is increased. The temperature can be subsequently increased, either before or after the pressure is decreased.
The pressure can optionally be repeatedly cycled (e.g., 2, 3, 5, 10, or even 100 or more times) between the elevated pressure and the initial pressure. Such cycling can be carried out at the initial temperature, at a low temperature (e.g., subzero temperatures such as between −40° C. and 0° C., or between −20° C. and −5° C.), or while the material is being cooled to a low temperature. In some cases, a sample at low temperature can be in the solid (i.e., frozen) state at the initial pressure, but in the liquid (i.e., molten, or thawed) state at the elevated pressure. In such cases, pressure cycling causes concomitant freeze-thaw cycling. The temporal pattern of pulsation can, optionally, be altered. During each cycle, the pressure is alternately raised and then lowered. The ratio of the time at high pressure to the time at low pressure is termed as the “pulsation pattern ratio.” A pulsation pattern ratio greater than 1:1 (e.g., 2:1 or more) can give optimal inactivation of contaminants in most cases, whereas a pulsation ratio less than 1:1 can give greater retention of properly folded, sensitive proteins.
The material being sterilized can be, for example, a biological sample, blood plasma, serum, living tissue, medical or military equipment, a foodstuff, a pharmaceutical preparation, or a vaccine. The material being sterilized can be initially contaminated with, for example, one or more of a bacterium, a virus, a fungus, a protist, a nucleic acid, or a protein.
Any of the new methods described above can also be used to produce vaccines against specific pathogens. For example, a suspension of pathogenic cells can be obtained, sterilized by one of the new methods (e.g., the method that involves pressure cycling, and potentially freeze/thaw cycling, at a subzero temperature), and combined with an adjuvant to produce a vaccine. If there are toxins present in the suspension, these can removed (e.g., after the sterilization step).
The new methods can be carried out in a pressurization vessel. The pressurization vessel can, for example, contain a gas (e.g., air or an inert gas such as nitrogen). The gas can be involved, for example, in a cavitation process. Cavitation is pressurization in the presence of a gas, followed by a rapid depressurization, resulting in the explosion of cells as microscopic gas bubbles form. This method of cell disruption can also be termed explosive decompression.
In some cases, it can be useful to include a phase-change catalyst (e.g., glass particles) in conjunction with the material to be sterilized. The catalyst can subsequently be removed by centrifugation or filtration, if necessary.
Materials sterilized by any of
Bradley David W.
Hess Robert A.
Laugharn, Jr. James A.
BBI BioSeq, Inc.
Fish & Richardson P.C.
McKane Elizabeth
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