Sterilization Method

This invention relates generally to the field of sterilization and more particularly to sterilization based on the use of ethylene oxide.

Sterilization by the application of boiling water or steam to the article to be sterilized has been carried out for many years. More recently there has arisen in certain fields, such as in medicine and in space exploration, the need to employ a different sterilant, because certain articles used in these fields cannot withstand the temperatures or the moisture associated with steam sterilization.

One sterilant that has become widely used is ethylene oxide because, not only is it an effective sterilant, but also its residues volatize relatively quickly from the article sterilized. Although ethylene oxide may be used by itself to carry out the sterilization, this is often not done because ethylene oxide is highly flammable. Instead ethylene oxide sterilant is generally used in a mixture with a flame retardant. The flame retardant, however, must complement the properties of the ethylene oxide or the beneficial effects of the ethylene oxide will be lost. Over the last two decades the flame retardant of choice for use with ethylene oxide in a sterilant mixture has been dichlorodifluoromethane, known in the industry as CFC 12. The most commonly used sterilant mixture is comprised of 27.3 mole percent (12 weight percent) ethylene oxide and 72.7 mole percent (88 weight percent) CFC 12. This mixture is commonly referred to in the industry as 12-88.

Recently a problem has arisen in the use of CFC 12 because it is one of the chlorofluorocarbons believed to cause significant damage to the ozone layer in the upper atmosphere. Accordingly, worldwide reduction and elimination of the use of CFC 12 is now underway. This has created a problem for the use of ethylene oxide as a sterilant.

As mentioned above, ethylene oxide may be used by itself as a sterilant. However the explosion danger of such use makes it acceptable for only a relatively few applications at selected locations where experienced and sophisticated handlers as well as suitable equipment and facilities are available at all times.

One flame retardant which is known for use with ethylene oxide is carbon dioxide. However because of the characteristics of carbon dioxide, a nonflammable ethylene oxide-carbon dioxide mixture contains less than 40 percent of the ethylene oxide per unit volume as does 12-88. Thus, sterilization must be carried out either at higher pressures or for longer contact times. Furthermore the large difference in the vapor pressures of ethylene oxide and carbon dioxide causes the mixture to separate upon withdrawal from the storage tank or cylinder, raising the danger of delivering a sterilant mixture rich in carbon dioxide, which won't sterilize, or rich in ethylene oxide, which is explosive.

Accordingly it is an object of this invention to provide an improved sterilant mixture employing ethylene oxide which overcomes the deficiencies of the known sterilants.

It is another object of this invention to provide an improved sterilization method using a sterilant mixture employing ethylene oxide which overcomes the deficiencies of the known sterilization methods.

The above and other objects which will become apparent to one skilled in the art upon a reading of this disclosure are attained by the present invention, one aspect of which is:

A sterilant mixture comprising from 14 to 25 mole percent ethylene oxide and from 75 to 86 mole percent 1,1,2,2,2-pentafluoroethane.

Another aspect of the invention is:

A method for sterilizing an article comprising contacting the article with an effective amount of a sterilant mixture comprising from 14 to 25 mole percent ethylene oxide and from 75 to 86 mole percent 1,1,2,2,2-pentafluoroethane.

FIG. 1 is a schematic representation of one sterilizer apparatus with which the method of this invention may be employed.

FIG. 2 is a graphical representation of certain flammability tests of the sterilant mixture of this invention carried out at atmospheric temperature and pressure.

FIG. 3 is a graphical representation of certain flammability tests for an ethylene oxide mixture formulated with the compound generally accepted as the substitute for CFC 12.

The invention is a sterilant mixture and a method of sterilizing articles using the sterilant mixture. The sterilant mixture is generally used as a gas or vapor.

The sterilant mixture of this invention comprises from 14 to 25 mole percent, preferably from 17 to 21 mole percent, ethylene oxide and from 75 to 86 mole percent, preferably from 79 to 83 mole percent, 1,1,2,2,2-pentafluoroethane. The ethylene oxide acts as the active sterilizer while the 1,1,2,2,2-pentafluoroethane acts as a flame retardant. At flame retardant concentrations than the specified minimum, sufficient flame retardancy may not be present in the mixture to avoid a potentially dangerous situation, and at flame retardant concentrations greater than the specified maximum, effective sterilization may not be possible without the use of undesirably high temperatures, pressures and/or contact times. The industrial shorthand term for 1,1,2,2,2-pentafluoroethane is HFC 125.

The sterilant mixture of this invention may be employed comprising only ethylene oxide and HFC 125. However, such a mixture has a relatively high vapor pressure which may result in difficulties in some situations. For example, some conventional low pressure cylinders may not be usable with a higher vapor pressure sterilant mixture. In addition, some of the higher vapor pressure HFC 125 may separate from the liquid mixture upon withdrawal from a storage vessel such as a cylinder, leaving an ethylene oxide-poor vapor in the storage vessel and sending an ethylene oxide-rich liquid to the sterilizer vaporizer. In order to address this problem the sterilant mixture of this invention may contain 1,2,2,2-tetrafluoroethane (HFC 134a), or 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124), or a mixture of these compounds, which will serve to lower the vapor pressure of the sterilant mixture of this invention while not significantly increasing its flammability or its ozone depletion potential. HFC 134a may be employed in a concentration up to about 30 mole percent and HCFC 124 may be employed in a concentration up to about 50 mole percent in the practice of this invention. Other compounds which may be present in the sterilant mixture of this invention include 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) which may help lower the cost of the sterilant mixture, other heavier molecules which may increase the heat capacity of the sterilant mixture, and inert nitrogen gas which may be used to increase the pressure in the sterilant container in order to propel the sterilant mixture into the sterilization chamber.

The sterilant mixture of this invention may be used to sterilize a great many articles. Examples of medical equipment and materials which may be sterilized include diagnostic endoscopes; plastic goods such as syringes; test tubes; incubators; pacemakers; rubber goods such as tubing, gloves, catheters and sheeting; instruments such as needles and scalpels; and other items such as dilators, pumps and intraocular lenses. In addition, the sterilant mixture of this invention may be used as a fumigant for items outside the medical field. These items include certain foodstuffs such as spices; furs, bedding, paper goods, and transportation equipment such as the cargo area of airplanes, trains and ships.

The sterilant mixture of this invention is effective against all forms of life, particularly unwanted insects, bacteria, virus, molds, fungi, and other microorganisms. Among the most difficult organisms to kill is B. Subtilus sbs. niger spores; however, even these organisms are effectively destroyed by the sterilant mixture of the invention.

The sterilant mixture of this invention may be prepared using any effective mixing technique well known to those skilled in the art. For example, each compound of the mixture may be pumped gravimetrically through a manifold into a sterilant container, and the container rolled to intermix the compounds into a homogeneous mixture. Alternatively, the compounds may be pumped into a mixing tank, recirculated in the tank until a fully homogeneous mixture is formed, and then pumped from the mixing tank into a sterilant container.

The sterilant mixture of this invention may be packaged in any storage containers of suitable design such as U.S. Dept. of Transportation (DOT) Specification 4BA 240, 4BA 300, 4BW 240 or other DOT specification cylinders or trailers of suitable working pressure. The sterilant mixture may also be packaged in American Society of Mechanical Engineers (ASME) storage vessels.

The storage cylinder may be delivered to the use site holding the sterilant mixture at a pressure generally within the range of from about 70 to 190 pounds per square inch absolute (psia) at 70.degree. F., and connected through a series of valves, control valves, vaporizer and appropriate conduit to a sterilizer to carry out the sterilization.

The sterilant mixture of this invention may be used with any commonly employed sterilizer known to the art. One such sterilizer is shown in schematic form in FIG. 1.

Referring now to FIG. 1, the item or items to be sterilized are placed within sterilization chamber 1 through door 2. Sterilizers such as is illustrated in FIG. 1 may range in size from desk-top models to room-size models and even larger. After the items are placed within sterilization chamber 1 and door 2 is shut, the chamber is heated generally to a temperature within the range of from 100.degree. F. to 140.degree. F. Generally the higher the temperature the shorter is the required exposure time. After the chamber is brought up to temperature, a partial vacuum is drawn inside the chamber by pumping out air through vent 8 by vacuum pump 9. The air removal serves both to prevent dilution of the sterilant mixture and to reduce the exposure pressure. Creating the appropriate vacuum generally takes from about 5 to 45 minutes depending on the item to be sterilized since some items can be damaged by sudden pressure changes. Since a moist microorganism is more susceptible to the action of the sterilant, water vapor is employed. In FIG. 1, water vapor from steam source 10 may be injected into chamber 1 through conduit 11. The water vapor is used to create a relative humidity within the chamber within the range of from 30 to 80 percent.

Sterilant mixture is passed from a source such as cylinder 3 through conduit 4 and filters 5 to vaporizer 6 wherein it is converted to a vapor. From vaporizer 6 the sterilant mixture is passed through conduit 7 into sterilization chamber 1 for the sterilization. The pressure at which the sterilization takes place within chamber 1 may be from about 20 to 40 psia. The sterilization time will vary and is dependent upon a number of factors including temperature, concentration, humidity level, the specific sterilant mixture employed, the chamber loading, the bioburden, the sterility assurance level desired and the material being sterilized. For example, some porous articles require shorter exposure time than do articles sealed in polyethylene bags. Moreover, some bacteria are especially resistant and thus take longer to destroy.

Following the required exposure time, the sterilant mixture is evacuated from the chamber by flushing with air, nitrogen, steam or carbon dioxide through inlet 12 and successive evacuations through conduit 8 by pump 9. The sterilized material is then removed from chamber 1 through door 2 and, if necessary, aerated for the removal of residual sterilant, before being used. The entire sterilization procedure may be monitored and controlled through control panel 13.

The following examples and comparative examples serve to further illustrate or distinguish the invention. They are not intended to be limiting.

A series of flammability tests were carried out to determine the flammability curves for ethylene oxide intermixed with HFC 125. The procedure was as follows. Ethylene oxide, HFC 125 and air, all at measured concentrations, were mixed sequentially in a 5 liter spherical vessel at atmospheric temperature and pressure. A hot nichrome wire, placed in the middle of the vessel, provided ignition energy to the mixture. Flame propagation, i.e. whether or not the mixture ignited and the flame propagated, was determined by temperature and pressure sensors installed at the vessel wall. The data for various mixtures is shown on FIG. 2. A clear data point indicates no ignition while a solid data point indicates ignition for that particular mixture. The curve shown in FIG. 2 represents the flammability curve for the mixture.

In order for a sterilant mixture to be non-flammable it must be non-flammable at all concentrations of air, i.e. from 0 to 100 percent air. Thus a straight line representing 0 to 100 percent air cannot cross below the flammability curve. A straight line from 0 to 100 percent air just tangent to but not crossing below the flammability curve represents the highest ethylene oxide concentration while maintaining the mixture non-flammable. Such a straight line is drawn in FIG. 2 and shows that for an ethylene oxide/HFC 125 mixture, the ethylene oxide concentration can be up to 19 mole percent and yet the mixture remains non-flammable for all concentrations of air.

For comparative purposes, the above-described procedure was repeated except that HFC 134a was used in place of HFC 125. HFC 134a has become generally accepted as the most likely replacement for CFC 12. This data is reported in FIG. 3. As is shown by the data, a mixture of ethylene oxide and CFC 134a is non-flammable only up to a maximum ethylene oxide concentration of 12 percent over the full range of air concentration.

The above example and comparative example serve to demonstrate that the sterilant gas mixture of the present invention exhibits a non-flammability significantly greater than that of the mixture formulated with the widely acknowledged replacement for CFC 12.

It is surprising that the sterilant mixture of this invention provides such beneficial results. As mentioned, the generally accepted substitute for CFC 12 is HFC 134a. This is because the physical properties of HFC 134a are similar to those of CFC 12 and also because HFC 134a contains no chlorine atoms which are believed to be the major cause of the ozone depletion effect of CFC 12. However, as was demonstrated in the comparative example, HFC 134a is not a good flame retardant. This is believed to be due to the absence of chlorine atoms. It is well known that the heavier halogens such as chlorine and bromine are good flame retardants and are routinely used in flame retardant chemicals. Thus it was unexpected that an ethylene oxide/HFC 125 mixture would have much greater non-flammability than an ethylene oxide/HFC 134a mixture since HFC 125 also contains no chlorine atoms. While not wishing to be held to any theory, applicants believe that one reason for the surprising advantages attained with HFC 125 is that HFC 125 has one less hydrogen atom than does HFC 134a and, that at the lower concentrations of the sterilant mixture in air, the amount of hydrogen available to react in a system containing ethylene oxide, HFC's and air plays an unexpectedly more significant role than would have been expected.