WO1989006121A1

WO1989006121A1 - Hydrogen peroxide vapor depyrogenation process

Info

Publication number: WO1989006121A1
Application number: PCT/US1988/004506
Authority: WO
Inventors: James R. Rickloff
Original assignee: American Sterilizer Company
Priority date: 1987-12-30
Filing date: 1988-12-16
Publication date: 1989-07-13
Also published as: CN1034673A

Abstract

A method is provided for depyrogenating surfaces. The method includes the step of exposing the surfaces to hydrogen peroxide vapor at a temperature less than about 100°C at a concentration and for a period of time sufficient for depyrogenating such surfaces. The period of time may also be sufficient for simultaneously sterilizing and depyrogenating the surfaces.

Description

HYDROGEN PEROXIDE VAPOR DEPYROGENATION PROCESS

BACKGROUND OF THE INVENTION

Field of the Invention

The present invention relates to depyrogenation methods, and more particularly to a depyrogenation method using hydrogen peroxide vapor.

Description of the Prior Art:

Endotoxins are high molecular weight complexes associated with gram negative bacteria. When the bacteria undergoes lysis, all endotoxin is released. Sterilization methods which kill bacteria are not always effective for removing or inactivating endotoxins. Whether by removal or inactivation, the effects of fever producing endotoxins, or pyrogens, must be eliminated from parenteral solutions or water used for injection in patients. In addition, the effects of pyrogens must be substantially eliminated from the surfaces of articles, such as medical instruments, solution bottles and tubing which come into contact with patients. There are few methods which simultaneously sterilize and depyrogenate. Dry heat has been shown to be effective for sterilizing and depyrogenating, but requires temperatures of about 250°C which is unacceptable for heat labile articles. The ability of hydrogen peroxide to depyrogenate has been known for some time. In 1947, A. Taub and F. Hart presented a paper "Detoxification Of Pyrogens By Hydrogen Peroxide In Some U.S.P. Injections", which was published in the Journal of the American Pharmaceutical Association, (1948). The paper described a methoe in which solutions were boiled with low concentrations of hydrogen peroxide to remove pyrogens. Hydrogen peroxide was shown to be an effective agent for the depyrogenation of oxypol gelatin used as a plasma substitute, and solutions of sodium chloride and dextrose. See Cherkiri, "Destruction of Bacterial Endotoxin

Pyrogenicity By Hydrogen Peroxide," 12 Immunochemistry 625 (1975). More recently, Makinen et al. U.S. Patent No. 4,648,978, issued March 10, 1987, describes a process for the continuous preparation of sterile, depyrogenated solutions which employs liquid hydrogen peroxide or ozone, and heat to simultaneously sterilize and depyrogenate solutions.

Additional methods of depyrogenating, without sterilizing, include heat treatment, hydrolysis with mild acetic acid or mild alkali, treatment with oxidizing agents, acetylation, hydroxylaminolysis and reductive cleavage by lithium aluminum hydride. Some of these methods are satisfactory only for simple solutions. Articles and solid surfaces, unlike solutions, cannot always be sterilized or depyrogentated by the combination of liquid hydrogen peroxide and heat. Methods using hydrogen peroxide vapor at temperatures below 80°C have been shown to be effective for sterilizing the surfaces of articles. See Moore et al. U.S. Patent No. 4,169,123 and Forstrom et al. U.S. Patent No. 4,169,124. Neither patent addresses the question of depyrogenation.

An object of the present invention is to provide a method of depyrogenating surfaces which does not depend on the application of the elevated temperatures heretofore required by the dry heat and the boiling hydrogen peroxide methods of depyrogenation. It is a further object of the present invention to provide a method for simultaneously sterilizing and depyrogenating surfaces at temperatures relatively lower than the temperatures required by the prior art methods.

SUMMARY OF THE INVENTION The present invention provides a method for depyrogenating surfaces by exposing such surfaces to hydrogen peroxide vapor at a temperature less than about 100°C at a concentration and for a period of time sufficient for depyrogenating such surfaces. The period of time is preferably sufficient for simultaneously sterilizing and deprogenating the surfaces. The method may also include the step of aerating the surfaces to remove any absorbed hydrogen peroxide following depyrogenation. The period of time may be less than or equal to about twenty-four hours and the concentration may be up to about 2 mg/1. Alternatively, the period of time may be less than about thirty minutes and the concentration may be up to about 10 mg/1.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT The method of the present invention employs hydrogen peroxide vapor at temperatures less than about 100°C, and preferably about 50-70°C, to simultaneously sterilize and depyrogenate surfaces. Generally, the method involves exposing the surfaces of articles to hydrogen peroxide vapor at a temperature below 100°C for a period of time sufficient for depyrogenating the surfaces. The concentration of the hydrogen peroxide vapor is preferably less than or equal to about 10 mg/1.

The hydrogen peroxide vapor concentration varies with the temperature employed. The greater the temperature, the higher the concentration of hydrogen peroxide vapor that can exist in the relevant air space. For example, at room temperature, about 20°C, the concentration may be 2 mg/1. At 55°C, the concentration may be 10 mg/1. Higher concentrations of hydrogen peroxide vapor lead to faster depyrogenation and therefore, lower exposure times. As the two examples set forth below illustrate, low concentrations may require a longer exposure time.

Example 1 Samples of 1 square centimeter 316 stainless steel coupons having a dose of 2200 endotoxin units dried onto the surfaces were suspended approximately two inches over a 30% hydrogen peroxide solution at 55°C for twenty-four hours. The vapor concentration contacting the samples was determined to reach 1.9 mg/1. A limulus amebocyte lysate (LAL) assay revealed that, even under less than ideal conditions, 99.97% of the endotoxin was inactivated. The conditions of Example 1 were much more crude than would be expected in most practical applications of the invention. The exposure time was therefore longer than it might ordinarily be under more sophisticated conditions.

Example 2 Samples of 316 stainless steel coupons having varying does of endotoxin dried onto the surfaces were exposed to a vapor phase hydrogen peroxide sterilization cycle at 55°C for twenty-five minutes. The hyrogen peroxide vapor concentration in the sterilizer reached a maximum of 10 mg/1. However, the sterilization cycle did not employ means necessary to maintain the concentration of sterilant in the chamber. Following completion of the cycle, LAL analysis revealed that the endotoxin activity in a sample initially having a dose of 6500 endotoxin units was reduced by 90.8% while another sample having an initial dose of 90,000 endotoxin units was reduced by 87.2%. A higher percentage of endotoxin destruction should be achievable either by increasing the exposure time or by increasing the concentration of hydrogen peroxide or both. The temperature of the depyrogenation process must be maintained within a range that will not harm the articles that are being depyrogenated. The preferred range is between about 50-80°C. Temperatures above 80°C but less than about 100°C and temperatures less than 50°C may also be effective.

The method of the present invention may also include the step of aerating the surfaces of the articles to remove any hydrogen peroxide which may have been absorbed by such surfaces.

Vapor phase hydrogen peroxide is particularly advantageous for depyrogenation because it can be used at relatively low temperatures and low concentrations. In addition, it simultaneously sterilizes the surfaces being treated. The natural tendency for hydrogen peroxide vapor to degrade into water and oxygen over time virtually eliminates concerns for contaminating the articles with potentially harmful substances that might be employed to chemically remove the depyrogenating agent which is required in the case of hydrogen peroxide liquid depyrogenation practices.

The articles may be packaged in any of a number of commercially available hydrogen peroxide vapor permeable packages to prevent recontamination after exposure to the process.

Claims

What is claimed is:

1. A method for depyrogenating surfaces comprising: exposing surfaces to hydrogen peroxide vapor at a temperature less than about 100°C at a concentration and for a period of time sufficient for depyrogenating said surfaces.

2. The method recited in claim 1 wherein said concentration is less than or equal to about 10 mg/1.

3. The method recited in claim 1 wherein said period of time is sufficient for simultaneously sterilizing and depyrogenating said surfaces.

4. The method recited in claim 1 wherein said period of time is less than or equal to about twenty- four hours and said concentration is up to about 2 mg/1.

5. The method recited in claim 1 wherein said period of time is less than about thirty minutes and said concentration is less than or equal to about 10 mg/1.

6. The method recited in claim 1 further comprising the step of aerating said surfaces to remove residual hydrogen peroxide following depyrogenation.