BE895729A - Low temp. sterilisation by contact with biocidal gas esp. formaldehyde - circulated from evaporating liq. soln. contg. higher proportion of sterilising agent - Google Patents

Abstract

A process for sterilising the surfaces of items, e.g. surgical instruments and medical equipment and appts. Sterilisation is effected by contacting the surface with a gas contg. a biocide which is obtained by evapn. of a liq. soln. The gas is circulated and kept in contact with the soln. which contains a higher proportion of sterilising agent in liq. and/or solid phase than in vapour phase. Pref. during the process, the surface is subjected to increased pressure from a carrier gas such as air or nitrogen. This takes place simultaneously with evapn. of the sterilising agent. The sterilising agent is employed at a temp. pref. between 0 and 100 deg. partic. 60 deg.C before the surface is contacted by the sterilising agent the surface temp. is brought as close as possible to that of the sterilising agent. The liq. soln. is pref. an aq. soln. of formaldehyde which may also include mineral salts, organic salts and/or glycols. The process is for low temp. sterilisation of items, partic. surgical instruments, and equipment and medical appts. e.g. polythene flasks, PVC tubing syringes, catheters, plastic sachets.

Description

       

  "Sterilization process using

  
The present invention relates to a gas sterilization process for the treatment of materials, objects or enclosures with one or more chemicals in the gaseous state.

  
The use of gas sterilization is essential to sterilize products or objects that cannot be subjected to high temperatures as conventionally used in methods

  
thermal sterilization, to highly energetic radiation such as gamma rays or to germicidal solutions such

  
that glutaraldehyde solutions,

  
In general, gas sterilization is mainly carried out by exposing the surfaces to be sterilized to biocidal gases such as ethylene oxide or formaldehyde.

  
The methods currently used have many drawbacks. Ethylene oxide, which is used on a very large scale, reacts slowly. Highly flammable, it is also very toxic, which can cause mutagenic effects in exposed people. It must be used at high concentrations (from 500 to 2000 mg / 1) which aggravate the risks (presence of residues in objects, high levels in the atmosphere of sterilization workshops, pollution of the environment). Formaldehyde, whose biocidal action has been known for a long time, presents significantly less risk than ethylene oxide, but the results of its use according to the methods currently used are very unsatisfactory.

  
If, under certain working conditions, sterilization cycles have proven effective against spore populations known for their resistance (B. subtilis, B, stearothermophilus) and directly exposed to formaldehyde vapors, inconstancy of results and differences of opinion which separate the users of these methods. Also, specialists in hygiene questions whether the devices and processes currently in place allow sterilization or, more precisely, disinfection.

  
Formaldehyde is generally used in two ways:
- by depolymerizing paraformaldehyde by heating,
- by injecting formaldehyde (approximately 40% formaldehyde solution) into a sterilizer using, moreover, saturated steam under subatmospheric pressure.

  
Although formaldehyde has a very effective biocidal activity at concentrations above 5 mg / 1, or even 2 mg / 1, sterility is not always achieved under these conditions of use which make it difficult to control the sterilization parameters, including gas concentration and relative humidity.

  
The present invention provides a sterilization process which consists in contacting, after possible preheating, objects, materials or premises with a gas mixture containing at least one biocidal agent, preferably formaldehyde, characterized in that this agent gaseous is obtained by evaporation from a liquid solution optionally in contact with a solid phase, that this gaseous agent is put into internal circulation, and kept in contact with the liquid solution. Objects, materials or enclosures are thus subjected to a controlled flow of gas, the composition of which is in equilibrium with the liquid solution.

   The present invention provides that the composition of the solution, possibly in equilibrium with a solid phase, and the composition of this solid phase are chosen so as to provide at the working temperature a gaseous phase capable of sterilizing the objects, materials or speakers carried. at this temperature.

  
The present invention further provides that, to this gaseous agent may be optionally added one or more other gases so as to increase

  
total pressure. This gas or mixture of gases is called "carrier gas".

  
Details and particularities of the invention emerge from the description below, given by way of nonlimiting example, and with reference to the accompanying drawings:
Figure 1 is a schematic representation of an apparatus for sterilizing different objects; - Figure 2 is a representation of the change in temperature, pressure, concentration of formaldehyde gas and relative humidity during a sterilization cycle performed in Example 1;
- Figure 3 is a representation of the change in temperature, pressure, concentration of formaldehyde gas and relative humidity during a sterilization cycle performed in Example 2;

  
FIG. 4 is a representation of the evolution of the temperature, of the pressure, of the concentration of formaldehyde gas and of the relative humidity during a sterilization cycle carried out in Example 3.

  
Referring to the accompanying drawings, Figure 1 illustrates the elements of a sterilization system.

  
The system comprises a treatment chamber 1 comprising a door 2 which can be closed after the objects have been loaded into the chamber.

  
The door 2 is provided with a heating means, and with regulation of this heating. The chamber is itself included in an envelope 3 allowing the circulation of a calorific fluid 4, connected to circulation, heating and regulating members of the heating means 5 at a variable temperature,

  
The room is connected to. a vacuum pump 6 via a conduit 7 comprising a valve 8 and a non-return valve 9.

  
The chamber is connected to a “vector” gas intake circuit comprising a means 10 for sterilizing a gas, for example a sterilizing filter, a conduit 11 comprising a valve 12 and a non-return valve 13,

  
A means 14 for heating the gas, controlled by a control means 15, can be shown before the sterilization means 10.

  
This heating means can possibly carry out thermostatization.

  
of the entire carrier gas line. This gas can be under pressure,

  
The chamber is connected to a steam generator 16 by a conduit 17 comprising a valve 18. The generator 16 is connected to a water supply 19 and to a temperature control system and /

  
or pressure 20.

  
The chamber is connected to a sterilizing gas generator 21. It comprises a liquid phase 22, a gas phase 23 and possibly a solid phase. It is included in an envelope 24, allowing the circulation of a calorific fluid 25, connected to circulation means, of heating

  
and thermal regulation 26. -

  
The heating and the temperature of the liquid phase 22 and possibly solid phase are controlled by a control means 27. This heating system can be part of the heating system of the chamber 1.

  
The gas phase is circulated from the gas generator 21 to the chamber 1 by a conduit 28 comprising a valve 29-, and distributed in the chamber by the diffusion plate 30.

  
The gas is taken up through the pipe 31, comprising the valve 32, and forced by

  
the gas pump 33 through the solution 22 before joining the conduit 28, The conduits, the valves and the gas pump are thermostatically controlled at the chosen sterilization temperature.

  
The evolution of the temperature and the pressure is automatically controlled and regulated by the programmable control means 34, which records by means of the probes 35 and 36 the temperature and the pressure, and consequently controls the valves, the vacuum pump, the heating elements, the gas pump.

  
A liquid solution optionally in contact with a solid phase containing a biocidal agent capable of developing a gas phase at the chosen sterilization temperature is introduced into the gas generator.

  
The heating circuits 5, 20, 26 and 27 are switched on.

  
The load to be sterilized is introduced into chamber 1, and door 2 closed.

  
The treatment chamber is then automatically subjected for a programmed time to steam from the steam generator 16, including

  
the flow rate is controlled by the valve 18 modulated so that the temperature of the chamber reaches the chosen sterilization temperature.

  
The gases present in the chamber are evacuated simultaneously by the vacuum pump 6. In a variant, a vacuum prior to the introduction of steam can be carried out.

  
After the required time, the steam supply is automatically cut off, while the vacuum pump continues to operate, for a preprogrammed time. The chamber pressure reaches a low value. The charge is hot and dry at this time. The operation of the vacuum pump is automatically interrupted, and the valve 8 closed.

  
The valves 29 and 32 of the gas generator are automatically opened,

  
and the gas pump 33 put into operation.

  
The atmosphere of chamber 1 is thus gradually loaded with a mixture

  
of sterilizing gas 23 originating from the evaporation of constituents from the liquid phase 22. After a certain time, the concentration of mixture of sterilizing gas in chamber 1 reaches equilibrium with the liquid phase of the gas generator maintained at constant temperature, and stays there.

  
The pressure in the chamber 1 reaches a value equal to the pressure prevailing before opening the valves of the gas generator, added to the pressure due to the gas phase 23 coming from the liquid phase 22 of the gas generator 21.

  
The carrier gas inlet valve 12 is then automatically opened,

  
and the heating system for this gas is simultaneously engaged, until a preprogrammed total pressure is obtained in chamber 1.

  
This total pressure can be lower, equal or higher than atmospheric pressure.

  
The gaseous atmosphere of chamber 1 is then maintained without change during the reaction time period required to achieve total sterilization.

  
The gas pump continues to operate during this time and maintains the balance of the sterilizing gas phase with the liquid phase.

  
After the required time, the gas pump is stopped, the valves 29 and 32 closed.

  
A vacuum is then automatically carried out by the vacuum pump 6, up to a determined pressure.

  
The carrier gas heating circuit is then automatically engaged and the carrier gas is admitted to the chamber up to a predetermined pressure.

  
The vector gas evacuation and admission cycle is repeated a sufficient number of times to assume the total evacuation of the sterilizing gas mixture from chamber 1.

  
Water vapor can be automatically admitted with the carrier gas, coming from the steam generator 16 by means of the conduit 17, during the admission of the gas. The temperature is controlled by the probe 35 and the control system 34.

  
Finally, the carrier gas is automatically admitted one last time into chamber 1, until atmospheric pressure is obtained.

  
Door 2 of the chamber is opened, the charge is removed, and the chamber is ready to receive a new charge.

  
 <EMI ID = 1.1>

  
that generators of gases or mixtures of sterilizing gases, with different gases or mixtures of carrier gases, at different temperatures and pressures maintained for varying durations of time during the cycle.

  
In addition, the details of structure, arrangement and arrangement of the apparatus described (for example, obtaining the gaseous biocidal agent by continuous bubbling in the solution) can be modified, and a certain number of elements can be replaced by other equivalent devices (for example, the heating circuits can be replaced by electrical resistances, or the heating circuits of the chamber and the gas generator can be combined in the same system, without leaving from ca- <EMI ID = 2.1>

  
The invention is illustrated by the following nonlimiting examples. Known populations of Bacillus subtilis (globigii) spores obtained by culture and sporulation of a reference biological indicator (American sterilizer Co "SPORDI" - trade name) were deposited on polyethylene supports and dried. They constitute biological indicators (I.B. in the text). These populations are then subjected, packaged or not, to a treatment intended to sterilize them. They are collected and cultured in a Tryptic Soy Broth solution at 30 g / l, at 37 [deg.] C for 14 days.

Example 1

  
The gas generator is filled with a 20.7% w / w solution of formaldehyde, 5.6% methanol and 73.7% w / w water.

  
At 60 [deg.] C, the corresponding gas phase is 9.8 mg / l of formaldehyde gas and at a humidity of approximately 90%,

  
A prior test conducted in the absence of any penetration difficulty for the gas, showed that two minutes of exposure to this mixture of gases at
60 [deg.] C is enough to kill 106 spores.

  
To test the sterilization capacity of the invention when the spores are difficult to access, the microbial populations and their supports were deposited in
- bags of welded polyethylene (thickness 20 µm),
- combined paper / plastic bags, of the peelable type, as used in hospital sterilization, welded (paper thickness 60 <EMI ID = 3.1>
- 10 ml and 2.5 ml syringes connected respectively to P, V, C tubes, plasticized 3.5 m and 5 m long and 2 mm inside diameter.

  
plasticized PVC tubes 5 m long and 2 mm in diameter

  
interior, connected at one end to a capsule with an internal volume of 1.1 ml, containing the biological indicators (this system is called "Helix type catheter");
- 20 ml polyethylene bottles, fitted with their caps loosened by a quarter turn,

  
For these tests, the following sterilization cycle was applied after thermostatization of the heating means 5, 15, 26, 27. at 60 [deg.] C:

  
1) an initial vacuum up to 0.1 bar (pumping time: 0.5 min.),

  
 <EMI ID = 4.1>

  
3) drying of the objects and the walls of the vacuum chamber until

  
obtaining a residual pressure of 0.05 bar (duration: 5 min.),

  
4) The production of the gaseous sterilization phase (duration 10 min,),

  
5) an air intake up to atmospheric pressure (duration: 0.5 min.), 6) proper sterilization (duration: 20 to 30 min.),

  
7) evacuation of the gas under vacuum, alternating with steam and air admissions (duration: 10 min.),

  
8) return to atmospheric pressure (0.5 min.).

  
Total duration: 50 to 60 minutes.

  
The evolution of the temperature, the total pressure in the chamber, the concentration of formaldehyde gas and the relative humidity in the chamber, as a function of time, is shown in FIG. 2.

  
In order to verify whether the formaldehyde residues possibly present in the polyethylene support of the indicators can inhibit the growth of germs surviving the sterilization treatment, a comparative culture of growth of germs was repeated 10 times. In a same tube containing the culture medium, an indicator having undergone autoclaving with formaldehyde and an indicator which has not undergone any formaldehyde treatment were introduced. -Bacterial growth appeared immediately in each of the 10 tubes which shows that the formaldehyde residue possibly present after treatment is insufficient to inhibit the growth of germs which would not have been destroyed by autoclaving with formaldehyde.

  
The results of the sterilization tests are presented in Table 1.

Example 2

  
The same liquid phase as in Example 1 is used in the gas generator.

  
At 40 [deg.] C, the corresponding gas phase is 5.1 mg / l of formaldehyde gas, and at a relative humidity of approximately 95%,

  
To test the sterilization capacity of the invention when the spores are difficult to access, the microbial populations and their support were deposited in "Helix" type catheters described in Example 1.

  
- Table 1

  

 <EMI ID = 5.1>


  
Table 2
 <EMI ID = 6.1>
 The evolution of the parameters of temperature, pressure, formaldehyde concentrations and relative humidity in the chamber is given in FIG. 3. The heating means 5, 15, 26, 27 have been thermostatically controlled at 40 [deg.] vs. The results of the sterilization tests are presented in Table 2,

Example 3

  
The gas generator is filled with a solution of 20.3% w / w of formaldehyde, 5.5% w / w of methanol, 29.1% w / w of water and 45.1% w / w of propylene glycol.

  
At 60 [deg.] C, the corresponding gas phase is 12.1 mg / l of formaldehyde gas and has a relative humidity of about 70%.

  
To test the sterilization capacity of the invention when the spores are difficult to access, the microbial populations and their supports were deposited in "Helix" type catheters described in Example 1.

  
The evolution of the parameters of temperature, pressure, formaldehyde concentration and humidity in the chamber is given in Figure 4.

  
 <EMI ID = 7.1>

  
The results of the sterilization tests are as follows:

  

 <EMI ID = 8.1>
 

CLAIMS

  
1. A method of sterilizing a surface, for example of material, objects, enclosures, by bringing this surface into contact with a sterilizing agent, characterized in that this agent is a gas or a mixture of gases containing at least one biocidal agent, that this agent is obtained by evaporation of a liquid solution, that this agent is put into circulation and kept in contact with the liquid solution, that the solution contains a quantity of sterilization agent liquid and / or solid state, greater than the quantity of sterilizing agent which is evaporated,


    

Claims (7)

1 to 3, characterized in that the liquid solution is an aqueous formaldehyde solution, optionally containing other components such as mineral or organic salts, polyols such as glycerin, propylene glycol, ethylene glycol, polyoxyethylene glycols, 2. Sterilization method according to claim 1, characterized in that that the surface to be sterilized is subjected to an increase in pressure by means of a gas or a mixture of carrier gas such as air, nitrogen, simultaneously with the evaporation of the sterilizing agent or as soon as the sterilizing agent content is obtained. 3, Process according to either of claims 1 and 2, characterized in that the temperature of the sterilizing agent is between 0 and 100 [deg.] C, particularly 60 [deg.] C, and in that the surface to be sterilized has previously been brought to a temperature close to or equal to that of the sterilizing agent. 4. Sterilization process according to either of the claims 5, Method according to any one of claims 1 to 4, characterized in that the surface to be sterilized and the gas mixture containing at least one biocidal agent are confined inside a fluid-tight chamber, at least part of the parts of which are in contact with the sterilizing agent has been brought at the temperature of the sterilizing agent. 6. sterilization process according to claim 5, characterized in that the surface to be sterilized is introduced into a treatment chamber, this chamber is partially evacuated to a subatmospheric pressure, which water vapor is introduced until obtaining of the desired temperature, a partial suction of this vapor being continuously carried out, that the admission of water vapor is interrupted, that the chamber is partially evacuated until the surface dries, that the the chamber is placed in communication with a liquid solution maintained at the chosen temperature, providing by evaporation a gaseous sterilizing agent, which the atmosphere of the chamber is circulated through the liquid solution by means of a gas pump , which is introduced as soon as the content of gaseous sterilizing agent is in equilibrium with the liquid solution in the generator, a gas or a mixture of carrier gases until a total pressure less than, equal to or greater than atmospheric pressure is obtained, thereby exposing the surface for the time required to obtain sterility, the gas pump remaining in operation, that the sterilizing agent is eliminated, that atmospheric pressure is restored and that the load is removed from the chamber. 7. Surface sterilization process, by bringing this surface into contact with a sterilizing agent, as described above, in particular in the examples given.