JPS609453B2 - Sterilization using seeded gas plasma - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION This invention relates to gas sterilization, which involves treating an object or substance with a gaseous or vaporous chemical to eradicate all microorganisms contaminating the object or substance. be.

The need for such sterilization methods arises from the many sterilization applications where heat sterilization, radiation sterilization, or liquid chemical sterilization cannot be performed. In practice, only two gases or vapors are used on a large commercial scale for surface sterilization purposes: formaldehyde vapor and ethylene oxide gas.

However, both have drawbacks. Formaldehyde vapor has been used as a vaporizing agent in hospitals, agriculture and industry for decades. This method has many limitations. Contact with steam at a relative humidity of at least 70% for at least 24 hours is required to kill strong aerobic and anaerobic bacterial spores at room temperature. This type of steam is highly corrosive and the steam is highly irritating. Also, high concentration of CH2
Since formaldehyde gas is stable only at temperatures above 80 oo in high humidity air, it is extremely difficult to maintain formaldehyde gas at a high concentration. At normal room temperatures, formaldehyde polymerizes quickly and dissolves easily in the presence of water. Gas sterilization with formaldehyde can therefore be considered a misnomer. This is because the introduction of formaldehyde gas into an enclosed space can be accomplished by dispersing either a wet film in which formaldehyde is dissolved or a solid formaldehyde polymer onto all available surfaces within the enclosed space. Because , will be done. Very contradictory and currently negative results have been reported in hospital disinfection, hospital rooms, bedding, etc., and in agricultural applications such as egg and adjacent egg farm sanitization. Formaldehyde vapor has very weak penetrating power, and when used in air with trace amounts of hydrochloric acid, it rapidly forms bis-(chloromethyl)-ether, a carcinogen, at 70:00 pm and relative humidity of 40%. In order to minimize the disadvantages of hospital applications mentioned above, new techniques have recently been developed.

It uses water vapor and formaldehyde gas at a pressure below atmospheric pressure in an autoclave at 80:00. This method kills most spore-forming microorganisms at normal hospital concentrations, reducing aldehyde residue on the equipment. This method requires an exposure time of 2 hours at a formalin concentration of 8 hours per cubic foot of autoclave. However, despite the prolonged contact and relatively high temperatures, this method is a
noofOfficialAmalyicaIChemi
sb) does not meet the strict requirements of the test. Formaldehyde vapor is difficult to handle at room temperature due to its toxic and irritating properties as well as the aforementioned, making it a satisfactory, rapid, and reliable method for most hospital and industrial applications. It is clear that this is not the case.

Over the past two decades, ethylene oxide (ETO) has become the most popular method of gas sterilization in both hospitals and industry.

Although ETO was initially seen as an ideal alternative to formaldehyde fumes, very serious limitations in terms of toxicity have recently come to the attention of health authorities. lET○
The average time required to sterilize a unit of medical equipment is 30°C.
However, the deairing process had to be continued for a long time.

For example, the deairing time of a medical device is 2 to 8 times in a deairing machine.
time, which varies between 1 and 8 days at room temperature. In rubber gloves, residue can cause hand burns, and in blood-carrying tubes, residue can damage red blood cells and cause hemolysis. Endotracheal tubes that are not adequately vented can cause tracheitis or tissue necrosis. In addition to the dangers due to the toxicity of ETO residues, other accidents have been reported due to the explosive nature of pure ETO.

When there is about 3% ethylene oxide vapor in the air,
If combustion is sustained and confined, a violent explosion will occur. To solve this problem, mixing diluent gases such as C02 or fluorocarbons with ETO is practiced in some commercial systems. Therefore, E.T.O.
Sterilization has become widely used not because it is an ideal sterilizing agent, but because it has rapid sporicidal ability without any drawbacks from a toxicological or environmental point of view. It is clear that this is because no other gas sterilization method was considered.

The present invention provides an alternative sterilization method to ETO sterilization that has the advantages of faster sporicidal action, no degassing time, no toxic residue, and no explosion risk. It is something.

Furthermore, the invention provides a more economical approach in terms of operating and investment costs when comparing the volume of material processed per unit time. A method is provided for sterilizing a surface, comprising contacting the surface with a cold gas plasma containing at least 9 parts of an aldehyde under subatmospheric pressure.

The term “sterilization” used here refers to Bacillus subtilis [the late cill
us subtilis ATCC (American
TypeCMure Collection) 1965
9] and Clostridrium spoogenes [Cl
ostridri skin sporogenes (ATCC3
584)].

This is because these bacteria are resistant microorganisms used in the trout sterilizer test required by the AOAC (Official Analytical Methods of the Association of Certified Analytical Chemists, 12th edition, November 1978). The eradication of the above two types of resistant spores by the AOAC method is effective against mycobacteria, small non-lipid viruses, medium lipid viruses and plant bacteria Lveg.
It will also automatically eradicate other less resistant microorganisms, such as E. nectaria. A better understanding of the sterilization mechanism of the cold gas plasma according to this invention will be possible by considering the physical structure of the highly resistant spores.

Figure 1 shows the representative structure of a typical bacterial spore. A typical bacterial spore is surrounded by an outer membrane, a loose sac characteristic of some spores, and contains proteins rich in 'a-disulfide (1S-S1) in a continuous manner from outside to inside. A multilayered coat, [b' a thick cortical layer containing murein polymers (or veptidoglycans);
{c} plasma membrane, and {d-koanu have spore protoplasts. The primary form of resistance of the spore to external agents consists of a proteinaceous outer coat containing keratin-like proteins.

The stability of the keratin structure is due to the large number of primary valence cross-links (disulfide bonds) and the secondary valence cross-links (hydrogen bonds) of competing polypeptides adjacent to each other. Keratin-like proteins are characteristically highly rutted, intolerant to aqueous salt solutions, dilute acids and basic solutions, and resistant to proteolytic enzymes and hydrolysis. The layered outer coat is
Therefore, it resists chemical changes and plays a major role in protecting the spores from external agents. The coat is believed to play an important role in the bactericidal action through physical or chemical alterations that affect the diffusion of killing molecules, excited atoms or radicals into the interior of the microbial protoplasts. Highly active agents must be selected to alter the multilayered outer coat so that they can further penetrate and interact within the cortical or protoplast regions, but the ionized gas plasma is reactive atoms, free radicals, that radically alter the protective layer of the spores;
and was found to be an excellent drug making molecule.

In accordance with the present invention, the presence of a small amount of aldehyde vapor in an ionized cold non-oxidizing gas plasma can eradicate sporulating and non-spore forming microorganisms. In the present invention, the object to be decontaminated is a small amount of aldehyde,
It is exposed to a continuous flow of a cold gas plasma, typically seeded with an aromatic, heterocyclic, saturated or unsaturated aldehyde.

Gaseous plasma contains ions, electrons and neutral particles (speci
It is a partially ionized gas consisting of es).

A cold gas plasma is formed by an electrical discharge of a gas.

In an electrical discharge, free electrons are subjected to a crab field and gain energy, which is then lost through collisions with neutral gas molecules. Energy transfer processes form a variety of highly reactive products, including metastable atoms, free radicals, and ions. In order for the energized gas produced by an electrical discharge to be properly called a "plasma", it must satisfy the requirement that the concentrations of positive and negative charge carriers are approximately equal.

The plasma used in this invention is a glow discharge plasma, also referred to as a "cold" gas plasma. This type of plasma has an average electron energy of 1 to 1 ratio V
It has the characteristic that the electron density is 1 to 1 and 2/ground. Unlike the conditions found in arcs or psuma jets, the electron and gas temperatures are very different due to the lack of thermal equilibrium. In glow discharge, the electron temperature is 10 times to 10 Mson higher than the gas temperature. The latter property is important when sterilizing thermally sensitive surfaces. The low temperature gas plasma used in this invention can be divided into two types of reactive components.

One consists of atoms, ions or free radicals, the other is high energy, small particles such as electrons and photons. In glow discharges, large amounts of ultraviolet radiation (UV) are always present. UV high energy photons (3.
3 to 6.2 V) respectively correspond to the maximum absorption of DNA (deoxyribonucleic acid) and other nucleic acids, resulting in a strong bactericidal effect. However, for spores up to one skin diameter, the photon energy is rapidly dissipated by the various spore layers, which limits photochemical reactions to the outer coat. Photon energy is somewhat limited to modifying the surface of thin layers and is therefore more effective when treating smaller non-spore-forming bacteria. In the case of highly resistant spores, the action of photons causes a partial change in the disulfide-rich proteinaceous coat, which facilitates the diffusion of free radicals, atoms, or excited molecules into the core region. .

In the present invention, the presence of small amounts of vaporized aldehyde monomer and free radicals in the cold gas plasma can significantly increase the overall biocidal action of the gas plasma.

Although the exact mechanism for increased sporicidal efficacy using aldehyde-seeded plasma streams is not completely understood, several mechanisms are possible.

For example, the presence of atomic or excited oxygen in the gas phase causes aldehydes to form very short-lived, reactive epoxides, other intermediates, and free radicals, which form the outer layer. It is thought that the diffusion of bactericidal groups increases by interacting with proteins and nucleic acids present in the coat. A possible second step of the diffusion of bactericidal groups is penetration into the interior of the cortical layer, whose main component is murein polymer (or veptidoglycan).

Murrein is a reticular large molecule with a cross-linked structure. Attack of the polymer by oxygen atoms and aldehyde radicals quickly perturbs and alters the rigid polymeric structure of the cortical layers, resulting in its destruction. Furthermore, a possible hypothetical transformation process is the synthesis of dipicolinic acid by aldehyde.

Since calcium and dipicolinic acid (DPA) are found in approximately equimolar amounts in spores, it has long been assumed that they form salt complexes that play a major role in spore resistance. The exact presence of calcium salts in the spores is an open question. The rapid access of aldehydes into the cortex, primarily the effect of gas plasma oxidation, may help block the amino groups of asparatic B-semialdehyde and directly interfere with DPA synthesis. This latter mechanism explains why a brief exposure to plasma gas in the presence of aldehydes can quickly destroy the spores or their ability to germinate.

Compared to other gas phase sterilization methods, the method of adding aldehyde seeds of this invention can achieve a sporicidal effect with a short time of contact with gas plasma. The germicidal action of low-temperature aldehyde-seeded gaseous plasmas can sometimes occur over a period of time, e.g. less than 10 minutes.
Since it is fast, the possibility of a reaction occurring inside the core or protoplast is somewhat small.

The central part of the spore is functionally called a vegetative body.
bud), which contains genetic traits, a repressed protein synthesis system, the enzymes and tissues and tissue materials necessary to initiate new enzyme synthesis, and also appears to store a supply of energy intermediates. The changes that occur in the outer coat, cortex and plasma membrane are sufficient to explain the sterilizing effect achieved in this invention.With regard to the oxidation phenomena in gaseous plasmas mentioned above, the use of ionized gas is similar to that of pure oxygen. but also oxygen-containing gases such as air, carbon dioxide, and N20.Although not as rapid as oxidizing plasmas, noble gases such as argon or helium, or nitrogen plasmas can also be seeded with aldehydes to sterilize. Therefore, the present invention allows spore killing times to be significantly reduced over those found with conventional oxidizing and non-oxidizing gas plasmas.

Excited ions, gas molecules, and photons alter the spore's protective layer, whereas activated aldehyde radicals penetrate the altered tissue and initiate a number of secondary lethal reactions that accelerate the sterilization process. Faster surface sterilization times result in a more economical process, with the potential to handle highly heat-sensitive materials that can be degraded by prolonged exposure to gaseous plasma, even at temperatures as low as 100 ohms. It provides: No significant corrosion or toxic residues are observed when adding aldehydes to the gaseous plasma. To produce the type of gas plasma required by the present invention, the carrier gas is excited using one of two radio frequency methods.

The first method consists of a ring type or induced discharge method, while
The second method is the parallel plate or capacitive discharge method. The processing area always consists of a chamber made of glass, plastic, or aluminum and maintained at subatmospheric pressure, usually between 0.1 and 10 Hg, into which gas and aldehyde vapors are introduced. A controlled flow of water is constantly being moved by the continuous suction of a vacuum pump. To excite the gases and vapors within the processing area, radio frequency energy emitted by the generator is passed through an induction coil wrapped around the processing chamber or outside the chamber or the entrance of the chamber. coupled by installed capacitive discharge plates. During processing, a radio frequency (RF) discharge glow spreads over substantially the entire processing chamber. In some cases, the electrodes can also be placed within the processing chamber. There are many ways to design electrical circuits that maximize the coupling of RF energy into the discharge gas. Optimization of the energy coupling, which can reach up to 90%, can be achieved by matching the gas load impedance to the impedance of the amplifier plate output circuit and tank coil.

The best impedance match is achieved by a tuning process consisting of adjusting a variable capacitor in a low impedance matching network connected by a coaxial cable between the reaction chamber and the generator. Newer designs couple the processing chamber directly to a relatively low power generator via a high impedance connector. This simplifies the electrical package by eliminating complex low impedance circuitry. During power coupling to a gas plasma, a small amount of power is always lost due to thermal effects. There is also an amount of power reflected back to the generator. To determine how efficiently energy is being released into the gas, an RF power meter is often added to the electrical circuit to monitor the difference between forward and reflected power. Gas plasma generators typically operate at 13.5 megahertz (MHz),
It is also effective at frequencies of 1 to 3 Sengawa z, and 100MHz
It may be up to z.

Gas plasma also has a frequency of 100 to 300,000M
It can also be formed at high frequencies in the microwave range in the Hz range.

From a practical standpoint, the preferred microwave frequency is 245 m.
It is a criticism of M. In the microwave region, atomic or excited molecular particles have a longer lifetime than particles formed at radio frequencies, and they persist even at considerable distance downstream in the glow-free region. While this is an advantage from an analytical standpoint, it is balanced out by the fact that the required electrical circuitry is more complex and therefore more expensive. When using microwave gas excitation and the processing chamber is usually designed as a cavity, the generator is generally a magnetron-type device, and the electromagnetic energy is conveyed by a standard radio wave guide. Regardless of the gas excitation frequency, it has been observed that the presence of small amounts of aldehyde vapor in the gas plasma significantly reduces the time required to kill sporulating and non-spore forming bacteria.

The present invention will be described in more detail with reference to the accompanying FIGS. 2-4.

Referring to the drawings, FIG. 2 shows the elements of a low temperature seeded plasma (LTSP) system for use in semi-continuous hospital-type sterilization for various purposes.

This system consists of a tunnel-shaped processing chamber 1, which has doors 2 at both ends, although only the left entrance side of the door 2 is shown. Plastic bottles, either toilet toilet or reusable, such as parenteral solutions or ophthalmic drug solutions, are loaded into the cylindrical chamber by a conventional automatic rail conveyor type system (not shown). After loading,
The front and rear doors 2 are automatically closed by an electric drive system 3. The loaded tunnel processing chamber 1 is then evacuated to subatmospheric pressure by means of a vacuum line system 4 connected to a trap 5 and a vacuum pump. The pressure below atmospheric pressure is usually about 0.1 to 1 m Hg inside the entire processing chamber 1. The gas to be ionized is then conveyed from a compressed gas line or vessel, the pressure and flow rate being controlled by a pressure gauge and a constant flow rate membrane or needle valve 8.

Aldehyde vapor is produced in vessel 9 by valving gas into liquid aldehyde to generate aldehyde vapor.
added to the gas stream from A flow meter 10 is installed between the aldehyde container 9 and the entrance of the tunnel chamber 1. A mixture of gas and steam is conveyed through a hollow pipeline 11 having a number of suitably arranged small holes so as to be uniformly distributed within the tunnel chamber. After the air in the tunnel chamber 1 has been largely evacuated, the gas-steam mixture is discharged into the area of treatment.

The gas-aldehyde vapor flow is adjusted by the dimensions and capacity of the tunnel 1. Plasma formation is performed using a matching network 13 and a wattmeter 14, and an AC (alternating current) standard current of 13.58M.
It begins with proper impedance matching by inductive and capacitive control, using an RF coil 12 that is part of an electrical circuit consisting of an RF generator 15 that converts to a high frequency ratio. RF generator 15 used to sustain plasma discharge
It must be able to withstand large variations in load impedance and essentially consists of a DC (direct current) power source, a crystal controlled RF resonator and a solid state buffer amplifier. Final amplification is performed by a power amplifier designed around the power amplifier tube to accommodate large variations in load impedance. According to this type of device, a single induction coil extending over the entire tunnel length is excited from a single power generator or a series of smaller coil sections are driven by a smaller modulating RF generator. It is activated from. During RF excitation, the gaseous plasma stream is continuously removed for the time necessary to achieve complete sterilization, typically 5 to 20 minutes.

The RF excitation is then automatically turned off, the gas flow is interrupted, and the vacuum pump is turned off. Air is automatically introduced into the tunnel chamber by means of a two-way valve 16. The doors at both ends are opened by an electrical mechanism and the sample container is automatically pulled out of the tunnel on a rail slide system. The tunnel chamber 1 is now ready to sterilize a new load. The total cycle time for sterilization is typically 10 to 3 minutes, depending on the material being processed and the power level. Figure 3 and 3
Figure A is a longitudinal cross-sectional view and a cross-sectional view, respectively, of the sterilization tunnel type processing chamber 1 shown in Figure 2.

The tunnel 17 is cylindrical in shape surrounding its main axis and consists essentially of two concentric cylindrical tubes 18 and 19 made of a highly resistive, non-reactive material such as glass or a polymeric material (e.g. polysulfone). , they are silicon type ○−
It is held in place by clamping down on the end flange of ring 20. When the inner pipe is assembled inside the outer pipe 18, an annular hollow 21 is formed, and the hollow is evacuated and brought to a pressure below atmospheric pressure by suction with a vacuum pump from the bottom closed part. A groove or hole 23 passes through the bottom of the inner cylinder 19 in order to create a subatmospheric pressure around the object to be decontaminated. The objects to be sterilized, for example plastic bottles of parenteral solutions, are reloaded into a parallelepiped-shaped basket 25, which slides on rail tracks 26 on wheels 27 equipped with loaf bearings. At the beginning of the sterilization cycle, the front and end doors 28 and 29 are automatically opened by an electrically operated device that rotates the doors 180° about the hinges 31. The front and end doors of the tunnel are generally made of UV-absorbing polymeric materials to prevent dangerous photon radiation from the chamber while maintaining maximum intensity of the gaseous plasma glow. The annular o-ring 32 serves to adequately seal the door against ingress of outside air. The reactive gas and aldehyde vapor are transferred to the small pipe 3 through the through hole 34.
3 into the processing tunnel. A small pipe for introducing gas and steam enters the tunnel at one end and is positioned at the top of the inner pipe 19 to ensure uniform diffusion of the gas over the entire length of the tunnel. In FIG. 3, RF induction coil 35 is wrapped around the main shell of processing tunnel 17. In FIG. Figure 4 is 100MH
Another embodiment of the present invention is shown which utilizes microwaves of z~30000 ohh per day.

The microwave gas plasma shown in FIG. 4 consists of a metal housing 35 similar to that used in conventional microwave ovens. Located within the housing are the main components of the low temperature microwave gas plasma system, which are supplied with A from the main output line 38 by means of a transformer, rectifier and magnetic field circuit housed in the output pack 37.
It consists of a magnetron that converts C current into microwaves.
High power beam of microwave energy (typical example is 245
0 MHz) is contained in waveguide 39 and faces away from blades 40 of fan 41, which rotates at low RPM (rotations per minute).

This fan bounces the output beam and reflects it off the walls, ceiling, back and bottom of the open room. Oven chamber 4
A microwave transparent Pyrex glass plate 43 is suspended approximately 1 inch above the metal bottom of the processing chamber. The instruments or substances 44 whose surfaces are to be sterilized are placed inside a tightly gas-tight container 45 which is connected to a glass plate 43 inside the oven chamber 42.
There is a battle layer on top. The container 45 comprises polymeric materials such as polypropylene, polyethylene, polystyrene and Teflon, cardboard, paper or special glass compositions. It can be constructed of any material that is transparent to microwave energy. The container 45 has a parallelepiped shape with a top lid 46 also made of a microwave transparent material. The top cover 46 has two openings 47 and 48, each equipped with a stopcock or valve 49, 50, for forming a gas-gas vapor mixture under a reduced pressure of 0.1 to 1 mm Hg. It has become.

The container 45 comprises two dishes 51 that support objects 44 to be sterilized, for example plastic bottles for ophthalmic drug solutions in the figure. The blood 51 is usually perforated to make the diffusion of the ionized gas plasma more uniform. A plastic cup 52 is fitted in the lower pan and contains an aldehyde solution 53 to be vaporized. Due to the thermal effect of microwaves, the aldehyde solution gradually vaporizes in the gas plasma when microwave energy is applied. The carrier gas to be ionized is supplied from a gas container (not shown).
A vacuum line including a constant flow rate valve 55, a pressure gauge 56, and, if desired, a flow meter is passed through the opening 47 to the container 45.
transported to. The low vacuum pressure necessary to empty the load container is provided through closure 48 by vacuum line 57 which connects to trap 58 and vacuum pump 59. The complete sterilization cycle for the embodiment of FIG. 4 is as follows.

Filling the dish 51 with the equipment to be decontaminated, placing the aldehyde solution in the cup 52 and applying a vacuum to remove the air;
The carrier gas is turned on and the microwave is turned on for the required time, typically 5-20 minutes to maintain a continuous plasma flow. At the end of the exposure, the microwave generator 41 is automatically turned off, the carrier gas flow is stopped, and the vacuum is restored by the bidirectional valve. The door of the microwave oven chamber 35 is then opened and the container 45 is removed by removing the flexible tube secured by the stopcocks 49,50. By quickly closing the stopcocks 49, 50, the loaded containers can be kept in aseptic conditions until it is necessary to move the decontamination device. The entire sterilization cycle generally takes 10 to 30 minutes. During processing, the surface temperature is 1
It never reaches 00oo. Oxidizing plasma leaves no detectable traces of chemicals on the treated surface.
Venting of decontaminated equipment is not necessary. Figure 2,
The semi-continuous sterilization process described above for the devices shown in Figures 3, 3A and 4 can be used to sterilize instruments if the package has small holes to allow entry of the ionized and excited gas mixture. It is also suitable for storing inside the package.

At the end of sterilization, the package is moved under sterile room conditions and a small sterile tape is then applied to the stoma to seal it. The sealing tape can be fixed either manually or by an automatic machine. The present invention can be used at various temperatures or pressures and by changing the flow rate of many types of gas.

Furthermore, the detailed structure of the above-mentioned devices, the size and shape of their sections, e.g. the dimensions of the tunnels or chambers and their arrangement, e.g. the introduction of aldehydes by evaporation into the macrowave field or into the carrier gas line. The introduction of aldehyde by means of a valve device, etc. may be modified within the scope of the present invention, and some components may be replaced by other equivalent means. For example, the RF coil could be replaced by a capacitive plate, and the magnetron could be replaced by a crystoroso or amplitron tube, each without departing from the spirit of the invention. The invention will now be illustrated by the following examples.

In these examples, the USD
Sporicidal data obtained using the A (U.S. Agriculture and Agriculture Bureau) approved smoke vaporization spore-killing test method are shown for all cases. Two highly resistant strains, namely B. s cape tilis (ATCCI9659) and CI. Sporohokones (ATCC) was used in the experiment. The spore carriers are a silk suture ring (L) and a porcelain cylinder (C) with 1 to 1 microorganisms as a dry spore load. The spore carriers were each suspended by a thin cotton thread attached to a gas pipe in the upper part of the treatment chamber. Also added to the bottom of the chamber were several spore test strips wrapped inside with surgical gauze 1/2 inch thick.

These control spore strips [AmericanS
“SPORDI” (registered trademark) by R company is the mother cmus
Glo tilis (glo!igii) and Bacillus
ss from an allothermophil female. It is said that it takes 60 minutes at 3000F to completely sterilize this S. costilis strain by heating in a dry state; It takes 1 hour and 40 minutes at 1300F to eradicate this. In all experiments, vacuum-dried B. Cape tilis and CI. Although acid-resistant AOAC strains of P. sporogenes were found to be much more resistant than SPORDI spores, for simplicity, SPO
The results for the RDI strips are not shown in the tables in the examples. Example 1 A series of experiments were conducted using the apparatus shown in FIG.

The carrier gases used for plasma formation were pure oxygen, argon, and nitrogen. Aldehyde vapors added to the carrier gas were prepared in a bulb using the following aldehyde solutions: formalin (8% formaldehyde), acetaldehyde, glyoxal, malonaldehyde, propionaldehyde, succinic aldehyde, butyraldehyde, glutaraldehyde, 2- Hydroxyadipaldehyde, crotonaldehyde, acrolein and penzaldehyde. The carrier gas flow rate is at room temperature (approximately 20°C to 25°C
) was 80 to 100 cc/min. The average internal pressure was 0.5 skin Hg. The radiation frequency is 13.5 meters
z, the average power density inside the plasma processing chamber is approximately 0.015
It was watt/earth. The minimum amount of aldehyde maintained within the continuous gas plasma flow was approximately 9/9/s. Table 1 below shows experimental results evaluating the effect of exposure time for various low temperature aldehyde seeded plasmas.

Control experiments are for gas alone (no aldehyde added) and non-oxidizing plasma (hydrogen gas) with formaldehyde or glutaraldehyde vapor added. For each species of spore-forming bacteria on specific carriers (rings or cylinders), IN-solid samples were used. In the table,
Mark the result as “Pass” or “Fail”
"P" indicates no growth on any of the samples of 1 to 1 mass, and "F" indicates no bacterial growth on any of the samples of 1 to 1 mass after appropriate incubation and heat shock. Indicates that there is. For clarity, we have omitted the "fail" test that preceded the first "pass" test. This is because it is clear that a short exposure time corresponds to a "fail" test. As is clear from the results in Table 1, a satisfactory bactericidal effect was obtained with a contact time of 10 to 3 females, but the individual contact times differed depending on the aldehyde used for vaporization. Example 2 Same as Example 1 except that the exposure time was about 1 flow of N and the output was continuously increased from 0.001 watt per unit of processing chamber to 0.015 to 0.1 watt/ground. A series of experiments were conducted under the same conditions.

As is clear from the results shown below in Omotekawa, sterilization was not carried out at the lowest power density, but 0.015 to 0.1
Even better results were obtained in the W/ range.

These results indicate that adding trace amounts of aldihydes to gaseous plasma increases the bactericidal power. It can be seen that oxygen is the highest carrier among the gases used in this series of experiments. All “fail” tests prior to the first “pass” test have been omitted from Table 0.
This is because low power densities clearly correspond to "fail" tests. Example 3 In another series of experiments, aldehydes were vaporized from a 2% solution, which corresponded to a consumption of 15 cc per run.

However, when gas plasma was sampled, the aldehyde concentration was 10/9/m at a flow rate of 100 cc/min.
It was found to be equal to in. This aldehyde concentration in the gas phase is approximately half that expected from a vaporized aldehyde solution, indicating that approximately half of the active aldehyde is deposited on the walls of the process chamber. Table m (below)
The aldehyde concentrations listed in are those observed in gas plasmas under normal processing conditions.

As is clear from the results, no increase in sporicidal activity was observed for any of the three gases used in the test at a low concentration of 0.1 M/min. A concentration of 9'min of 1 gives contradictory results.

At a concentration of 10w9'min, most aldehydes enhance the sterilization efficiency of gas plasma.

At a 9'm;

Shirafune Example 4 Table W below was observed when a single aldehyde was replaced with a mixed composition of two aldehydes or a mixed formulation composition containing an aldehyde and a non-aldehyde biocidal compound, such as phenol. Show the results.

The mixed composition shows the same results as a single aldehyde solution as long as the total concentration of aldehyde is the same in the two treatments. The presence of phenol does not affect the efficiency of aldehydes as bactericidal enhancers in gaseous plasmas. Although not reported in Table W, a number of experiments were conducted using various solutions of other fungicides in addition to phenol.

The aldehyde concentration was kept the same and the following ingredients were added in equal concentrations: halogen compounds such as chloroisocyanate, e.g. triclo-S-triazinetrione and iodophor, e.g. PVP-iodine complex; salts such as selenium sulfide; alcoholic solutions of zinc undecylenate; quaternary ammonium salts such as cetylpyridinium chloride; organic sulfur compounds such as nitrogen of aliphatic amines such as methylene bisthiocyanate and N-alkyl trimethylene diamine. Compound.

In both cases, no synergy was detected due to the presence of these mystery agents in the gas phase. Note, however, that there is a slight increase in activity (doping effect) when plasma vaporization contributes to chemical salt dissociation with release of halogen. Severe corrosive effects of ionized halogens have also been observed, making the use of such chemicals in seeded cold plasma gases impractical. Mifune Example 5 Experiments with other rows were conducted using the apparatus shown in Figure 4.

Since these experiments were conducted at higher frequencies than in the case of Examples 1-4, the microwave glow discharge was more uniform inside the polysulfone experimental vessels. The gas plasma pressure (2℃Hg) is the same as when the microwave discharge is DC or RF.
It was slightly higher than the previous test because it is more difficult to start and maintain at a lower pressure (≦1 Hg) than a discharge.
Due to the greater lifetime and efficiency of free radicals and ionized particles in microwave gas plasmas, the contact time is
Shortened to 0 minutes.

A microwave-transparent polysulfone-plastic container with dimensions of 15 x 35 x 25 cm (capacity: 16.3 cm) was used. Average density in the resonant chamber approximately 0.02 watts/c
The electromagnetic energy of c has a nominal frequency of 2540 MHz (earth 2
9M ratio). Gas flow rate is 900cc~100cc
It was adjusted to 0 cc/min, which corresponds to an average aldehyde concentration in the plasma phase of 18 m9/min. Approximately 18 cc of each 2% by weight aldehyde solution was evaporated during the 10 minute treatment.

This amount corresponds to approximately twice the amount actually present for reactions in gas plasmas. From the results shown in Table V, it can be seen that in electromagnetic continuous gas plasma discharge, a small amount of aromaticity,
Seeding with heterocyclic, saturated or unsaturated aldehydes is shown to increase disinfection efficiency. When furfural is vaporized, the concentration in the oxygen fluid is 0.0018
It was % by volume. This is because furfural is 2.
Due to its low explosive limit of 1% by volume. 2%
The aqueous solution was kept below the flash point of the open cup aldehyde, which was about 68 oo, during constant vaporization.

Other than penzaldehyde, other aromatic aldehydes such as thiophene aldehyde and pyridine-2-aldehyde showed qualitatively the same behavior. P Ship Summarizing the disclosure of this specification, the present invention provides a plasma gas sterilization method that has substantial advantages over conventional gas phase sterilization methods.

. Modifications may be made within the scope of this invention.

[Brief explanation of drawings]

Figure 1 shows a representative bacterial strain. FIG. 2 shows a semi-continuous hospital sterilization apparatus, and FIGS. 3 and 3A are longitudinal and cross-sectional views, respectively, of the sterilization chamber of FIG. 2. FIG. 4 shows another apparatus for use in the method of the invention using microwaves. Code in the figure: a...
...Disulfide-rich protein-containing multilayer coat;
b... Thick cortical layer containing murein; c... Plasma membrane: d... Core or saturated protoblast: e...
... Outer membrane (filled loose surrounding bag); f ... Core wall; 1 ... Processing chamber; 2 ... Door; 9 ... Aldehyde container; 10 ... ...Flowmeter; 17...
...Tunnel type processing chamber; 18, 19...Concentric cylindrical tube; 20...0-ring: 23...
・Hole or groove: 25... Basket; 35...
... Housing: 39 ... Waveguide; 41 ...
... Fan: 42 ... Oven chamber; 43.
...Glass plate; 44 ...Sample: 4
6... Upper lid: 52... Cup: 53.
...Aldehyde solution; 58...Trap; 59...Vacuum pump. minute 1 wind fin Z figure rudder cicada float figure 44

Claims (1)

[Claims] 1. A pressure lower than atmospheric pressure, preferably about 0.1 to 10
A method for sterilizing surfaces, characterized in that the surfaces are brought into contact with a cold gaseous plasma containing at least 10 mg/l of aldehyde under mmHg. 2 The aldehyde is formaldehyde, acetaldehyde, glyoxal, malonaldehyde, propionaldehyde, succinaldehyde, butyraldehyde, glutaraldehyde, 2-hydroxyadipaldehyde,
The method according to claim 1, characterized in that the acrolein, crotonaldehyde, benzaldehyde or furfural is used. 3. Claim 1 or 2, characterized in that the gas plasma is produced by electromagnetic excitation of oxygen, argon, helium, nitrogen, carbon dioxide, nitrogen oxide, or a mixture of two or more of these gases. The method described in section. 4 Electromagnetic excitation is radio waves of 1 to 100 MHz or 100 to 100 MHz
4. The method according to claim 3, wherein the method is carried out using electromagnetic discharge in the microwave range of 300,000 MHz. 5. The gas plasma according to claim 3 or 4, characterized in that the gas plasma is confined inside a fluid-tight chamber, and the electromagnetic field density in the closed chamber is at least 0.001 watts/cm^3. Method. 6. Claim 1, characterized in that the aldehyde is introduced into the continuously formed gas plasma as a mixture with a carrier gas of a plasma gas precursor.
The method according to any one of Items 5 to 5. 7. A method according to any one of claims 1 to 6, characterized in that the gaseous plasma also contains at least one sterilizing agent other than an aldehyde. 8. Process according to claim 5, characterized in that the aldehyde is introduced into a gas plasma produced continuously from a gas plasma source located in a closed chamber.