WO1991007193A1

WO1991007193A1 - Method of sterlizing with low vapor pressure sterilants

Info

Publication number: WO1991007193A1
Application number: PCT/US1990/006610
Authority: WO
Inventors: Robert W. Childers; Arthur L. Cummings
Original assignee: American Sterilizer Company
Priority date: 1989-11-16
Filing date: 1990-11-13
Publication date: 1991-05-30
Also published as: JPH04503026A; EP0453549A1

Abstract

A method of sterilizing using low vapor pressure sterilants comprises the steps of vaporizing a liquid to produce a vapor phase sterilant having a low vapor pressure. The vapor phase sterilant is heated beyond the vaporization temperature to increase the vapor pressure thereof. The increased vapor pressure is used to deliver the heated vapor phase sterilant to an enclosure. The heated vapor phase sterilant is cooled to the enclosure's temperature. The heat released by the vapor phase sterilant as it cools is absorbed by the enclosure without significantly increasing the enclosure's temperature. The concentration of vapor phase sterilant in the enclosure is maintained until sterilization is achieved.

Description

METHOD OF STERILIZING WITH LOW VAPOR PRESSURE STERILANTS

BACKGROUND OF THE INVENTION

Field of the Invention

The present invention relates to sterilization systems and more particularly to sterilization systems using vapor phase sterilants.

The need exists in many situations to sterilize the interiors of various types of enclosures ranging from simple containers to entire rooms. For example, clean rooms are needed to manufacture certain kinds of microelectronic articles and pharmaceuticals. Laboratory spills may occur that involve highly contageous substances thereby unexpectedly contaminating an area requiring that the laboratory be decontaminated or sterilized. Other examples may involve the interiors of enclosures such as incubators or the like which may require sterilization to rid them of pathogenic contaminants.

Systems have been proposed to meet such diverse needs. For example, in U.S. Patent Application serial No. 070,271, entitled Flow-Through Vapor Phase

Sterilization System, filed July 6, 1987 and assigned to the same assignee as the present invention, a system for delivering vapor phase hydrogen peroxide to an enclosure is disclosed. Certain liquids exist which, when vaporized, produce vapors having a low vapor pressure. Vapor phase hydrogen peroxide is an example of a low vapor pressure sterilant. Because of low pressure, here the vapor pressure cannot be relied upon to provide sufficient driving force to propel the sterilant to the enclosure to be sterilized. If some carrier agent is not utilized to transport the sterilant vapors to the enclosure, a long time can elapse before the sterilant vapors reach the enclosure and become distributed throughout the enclosure. In the case of sterilant vapors which are unstable, can degrade, or otherwise become ineffective (such as vapor phase hydrogen peroxide) , rapid delivery and distribution is critical to sterilization efficiency. Carrier agents such as air, nitrogen, freon, etc. can be used to deliver the low vapor pressure sterilant to the enclosure. For example, in the aforementioned patent application, air is used as the carrier agent to deliver the vapor phase hydrogen peroxide to the enclosure. However, the carrier agent may interfere with penetration of the sterilant into the articles within the enclosure to be sterilized. The carrier agent may reach the articles or surfaces to be sterilized before the sterilant and inhibit the diffusion process of the vapor into the item to be sterilized. The carrier may pressurize the enclosure thereby inhibiting the flow of additional sterilant vapors into the enclosure. The carrier may also create a disposal problem. Thus the need exists for a method of delivering sterilant vapors having a low vapor pressure to an enclosure without the aid of carrier agents.

SUMMARY OF THE PRESENT INVENTION The present invention is directed to a method of sterilizing using low vapor pressure sterilants, comprising the steps of vaporizing a liquid to produce a vapor phase sterilant having a low vapor pressure. The vapor phase sterilant is heated beyond the vaporization temperature to increase the vapor pressure thereof. Alternatively, the vapor phase sterilant is initially produced at the desired elevated temperature. The increased vapor pressure is used to deliver the heated vapor phase sterilant to an enclosure. The heated vapor phase sterilant is cooled to the enclosure's temperature. The heat released by the vapor phase sterilant as it cools is absorbed by the enclosure without significantly increasing the enclosure's temperature. The concentration of vapor phase sterilant in the enclosure is maintained until sterilization is achieved.

According to one embodiment of the invention, the liquid which is vaporized is hydrogen peroxide.

According to another embodiment of the invention, the enclosure is evacuated before the heated vapor phase sterilant is delivered. Evacuation may continue at a rate equal to the rate at which heated vapor phase sterilant is being delivered to the enclosure.

The method of the present invention speeds up while simplifying sterilization processes relying on low vapor pressure sterilants without introducing a carrier agent. Those and other advantages and benefits of the present invention will be apparent from the Description of a Preferred Embodiment hereinbelow.

BRIEF DESCRIPTION OF THE DRAWINGS

In order for the present invention to be easily understood and readily practiced, a preferred embodiment will now be described, by way of example only, with reference to the accompanying figures wherein:

FIG. 1 is a block diagram illustrating an apparatus for carrying out the method of the present invention; and

FIG. 2 is an exemplary graph of pressure vs. time for a sterilization cycle which may be performed using the method of the present invention. DESCRIPTION OF A PREFERRED EMBODIMENT The method of the present invention may be carried out with an apparatus 10 illustrated in FIG. 1. The reader should understand that the method of the present invention may be carried out with a variety of different devices arranged in various combinations. The particular apparatus 10 illustrated in FIG. 1 is disclosed for purposes for illustration only. The method of the present invention consists of operating pump 22 to evacuate an enclosure 20 which is to be sterilized. The enclosure 20 may be a discrete enclosure such as an incubator or sterilizer or it may be an entire room. Such evacuation reduces the partial pressure of all gasses and vapors within the enclosure 20.

Saturated sterilant vapors are generated at a high temperature. That may be achieved through the use of a vaporization chamber 12 which receives a liquid to be vaporized from a liquid reservoir 14.

The liquid to be vaporized is contacted with a heated surface 16 of the vaporization chamber 12. Such contact vaporizes the liquid to produce a vapor phase sterilant. Upon vaporization, certain liquids, such as hydrogen peroxide, produce a vapor phase sterilant having a low vapor pressure. Thereafter, the vapor phase sterilant may be heated in a heater 18 to increase the vapor pressure. Alternatively, the heated surface 16 may be at such an elevated temperature so as to produce the high temperature saturated vapor when the liquid contacts that surface.

The high temperature saturated vapor phase sterilant can, by virtue of the increased vapor pressure, propel itself through a distribution line 19 into the evacuated enclosure 20. The heated vapor phase sterilant's momentum may not be sufficient to carry it throughout all parts of the enclosure 20. Therefore, diffusion must still be relied upon to deliver the sterilant vapor a short distance into various intricacies of the enclosure 20 and/or articles to be sterilized which may be located within the enclosure 20. Once the heated vapor phase sterilant enters the enclosure 20, it will expand to fill the available space in the cooler enclosure. Cooling accompanies expansion so care must be taken not to exceed the new vapor pressure (i.e. saturation) limits for the sterilant vapors at this new lower temperature. The low pressure that is maintained within the enclosure 20 promotes the diffusion process of the sterilant vapors the short distances into all of the intricacies of the enclosure 20 and/or articles within the enclosure 20. The rate of diffusion is dependant upon the concentration gradient, and concentration depends upon both the mass of the heated vapor phase sterilant being diluted as well as the mass of the diluting agent. By evacuating chamber 20, the concentration gradient is increased by reducing the mass of the diluting agent such that diffusion is promoted as previously stated.

As the heated vapor phase sterilant cools, the latent heat released by the vapor phase sterilant is sufficiently small that the enclosure 20 absorbs that heat without significantly increasing its temperature.

According to one embodiment of the invention, a continuous but low flow velocity stream of vapor phase sterilant is produced. The enclosure 20 is evacuated by pump 22 at a rate which is equal to the rate at which the hot saturated vapor phase sterilant vapor is introduced into the enclosure 20. Thus, a steady state condition is established which can be maintained almost indefinitely because as a portion of the sterilant vapor degrades or otherwise becomes ineffective, it is replaced by fresh sterilant vapor. As previously mentioned, vapor phase hydrogen peroxide has a low vapor pressure. Table 1 provides a comparison of the vapor pressure of thirty weight percent vapor phase hydrogen peroxide to that of saturated steam.

TABLE I

Corresponding Absolute Vapor Pressure Vapor Temperature 30% VPHP Saturated Steam

1,543 mm Hg

2,165 mm Hg

In the table, the vapor pressure for 30% VPHP is for 30% H„0 vapor and 70% H„0 vapor not for the vapor above a .solution of 30% aqueous H O . Those are not naturally occurring vapors.

Note that at room temperature (20°C) , the temperature at which sterilization takes place according to one embodiment of the method of the present invention, the vapor pressure of vapor phase hydrogen peroxide and water is only 4.3 mm Hg.

Saturated steam is typically used as a sterilant at 121°C and 132°C where it has a vapor pressure of 1,543 mm Hg and 2,165 mm Hg, respectively. That is 350 to 500 times greater than the vapor pressure of vapor phase hydrogen peroxide at 20°C. By generating vapor phase hydrogen peroxide at 60°C or higher, the vapor pressure can be increased significantly to 48.2 mm Hg which is sufficient to propel the vapor phase sterilant rapidly through the evacuated distribution line 19. If the distribution line 19 is not evacuated, there would be 760 mm Hg of air pressure impeding the flow of the sterilant. If humid air is present, an even greater impediment is presented for two reasons. First, the ambient pressure would exceed 760 mm Hg. Secondly, water vapor would be present in both the air and the 30% weight percent vapor phase hydrogen peroxide so the saturation limits would "be reduced. A humidity of only 10% in the air would lower the saturation limits of 30% vapor phase hydrogen peroxide to 41.1 mm Hg of partial vapor pressure at 60°C (See Appendixes A and B) . Thus, the pressure gradient that promotes flow is decreased by nearly 15% by only 10% moisture in the air.

Assume the enclosure 20 has a volume of 1,000 cubic feet. At 25°C, that enclosure can maintain 6.81 mg/L of 30% hydrogen peroxide solution in the vapor state. That corresponds to a pressure rise of 6.0 mm Hg. See Appendix A. Generating saturated vapor at 60°c results in a vapor having a concentration of 48.759 mg hydrogen peroxide and water per liter

(14.628 mg hydrogen peroxide per liter; see Appendix A) and a pressure of 48.2 mm Hg. That pressure differential (48.2 mm Hg - 6.0 mm Hg) can act as a driving force to propel the vapors from the vaporizer to the enclosure. When the vapors reach the enclosure, they will expand to fill the available volume. That expansion cools the vapors.

Energy Given up when Hydrogen Peroxide Vapor Cools

The energy given up by 30% hydrogen peroxide vapor as it cools is not directly available in the literature; however, it can be calculated indirectly as follows:

E = (Enthalpy of vapor at 60 deg - Enthalpy of vapor at 25 deg) EQN1

= (Enthalpy of liquid at 60 deg + energy of vaporization at 60 deg) - (Enthalpy of liquid at 25 deg + energy of vaporization at 25 deg)

= (Enthalpy of liquid at 60 deg - Enthaly of liquid at 25 deg) + (Energy of vaporization at 60 deg - Energy of vaporization at 25 deg)

The Enthalpy of 30% liquid is not available in the literature either; however, the difference in enthalpies can be readily calculated.

m*C * (60-25) = Difference in Enthalpies

Where m is the mass of liquid and

C is the specific heat of the liquid wh be obtained from Table II in Appendix C.

The energy of vaporization is also not readily available from the literature; however, it can also be calculated quite easily. Heat of Vaporization of 30 wt % Solution = [ (.30) (Heat of Vaporization of 100% Peroxide) ] + [ (.70) (Heat of Vaporization of Water) ] - Heat of Solution

524 cal/gram at 25 deg C = [ (.30) (362.6 cal/gm) ] + [ (.70) (583.4 cal/gm) ] - (-6.7 cal/gm)

506.5 cal/gm at 60 deg C = [ (.30) (352.1 cal/gm) ] + [ (.70) (563.1 cal/gm) ] - (-6.7 cal/gm)

The heats of vaporization of 100% hydrogen peroxide were obtained from Table III in Appendix C. The heats of vaporization of water were obtained from saturated steam tables which are widely available in the literature. The heat of dilution was obtained from Table IV in Appendix C. Note that the heat of vaporization for 30% hydrogen peroxide at 25 deg C calculated above agrees with the value in Table V in Appendix C.

Equation 1 then becomes E = m [(.823 cal/gm-deg C * 35 deg C) + 506.5 cal/gm - 524 cal/gm] EQN2

Assuming 30% hydrogen peroxide, the enclosure 20 can hold (6.811 mg/L) * (28.32 L/Cu ft)* (1000 cu ft) * (lgm/lOOOmg) or 192.9 grams. Using that value for m in Equation (2) yields a value of 2,180 gram calories or 8.65 BTU's.

In an enclosure having a volume of 1,000 cubic feet, 8.65 BTU's can easily be absorbed without measurably increasing the temperature of the enclosure. Thus, the greater the enclosure's ability to absorb heat without measurably increasing in temperature, the higher the temperature may be elevated above the sterilization temperature thus increasing the vapor pressure and promoting more rapid delivery.

Comparing vapor phase hydrogen peroxide to ethylene oxide, the 12% ethylene oxide 88% freon sterilant used in many ethylene oxide sterilizers is typically introduced into a chamber evacuated to 90 mm Hg absolute and controlled at 1,174 mm Hg. Thus, the total vapor pressure which is used to deliver the sterilant is 1084 mm Hg. The concentration of ethylene oxide sterilant is approximately 350,000 ppm. 30% vapor phase hydrogen peroxide at 20°C has a vapor pressure of only 4.3 mm Hg and a concentration in dry air of approximately 5,660 ppm (1047 ppm hydrogen peroxide, 4613 ppm water) .

One example of a sterilization cycle which may be carried out using the method of the present invention is illustrated in FIG. 2. As is seen in the figure, heated vapor phase hydrogen peroxide may be introduced into the evacuated enclosure 20, partially removed by suction, replenished, again partially removed and again replenished. The partial removal and replenishing of vapor phase hydrogen peroxide is repeated three additional times for a total of five pulses. Thereafter, the enclosure 20 is partially cleared with air to 210 mm Hg, then again evacuated. The steps of partial removal and partial replenishing for five pulses and partial clearing with air and evacuation are repeated four more times. Thereafter, after approximately 140 minutes, the enclosure may be aerated by alternating between atmospheric pressure and a vacuum.

According, to another embodiment of the present invention, the vacuum pump 22 may be operated to generate a continuous flow of heated vapor phase sterilant through the enclosure 20. The continuous flow of vapor phase hydrogen peroxide, which is generated and propelled according to the teachings of the present invention, can be successfully delivered to the enclosure 20 despite the unstable nature of vapor phase hydrogen peroxide. Once delivered to the enclosure 20, the vapor phase hydrogen peroxide then diffuses over the short distances to effect complete sterilization of non-absorbing materials. The flow- through velocity must be low enough to prevent the flow from interfering with the diffusion process. The removal of old vapors and introduction of fresh vapors may be continuous or intermittently controlled within predetermined ranges, i.e. 2 + 0.2 mm Hg absolute pressure or 90 + 10% saturated. The important part of the cycle, however, is the long distance delivery under a vacuum which is accomplished by virtue of the sterilant's own vapor pressure.

The sterilant used in conjunction with the present invention may be a single vapor or a multi- component vapor such as 30% vapor phase hydrogen peroxide and 70% water vapor.

While the present invention has been described in conjunction with a preferred embodiment thereof, many modifications and variations will be apparent to those of ordinary skill in the art. This disclosure and the following claims are intended to cover all such modifications and variations.

Claims

What is claimed is:

1. A method of sterilizing using low vapor pressure sterilants, comprising the steps of: vaporizing a liquid to produce a vapor phase sterilant, said vapor phase sterilant being at a temperature above that needed for vaporization so as to have an increased vapor pressure; using the increased vapor pressure to deliver the vapor phase sterilant to an enclosure; cooling the vapor phase sterilant to the enclosure's temperature, the enclosure absorbing the heat released by said vapor phase sterilant without significantly increasing in temperature; and maintaining the concentration of vapor phase sterilant in the enclosure until sterilization is achieved.

2. The method of claim 1 wherein the step of vaporizing a liquid includes the step of vaporizing hydrogen peroxide.

3. The method of claim 2 additionally comprising the step of evacuating the enclosure prior to delivery of the vapor phase sterilant.

4. The method of claim 3 additionally comprising the step of continually evacuating the enclosure at a rate equal to the rate at which the vapor phase sterilant is delivered to the enclosure.