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ROOM TEMPERATURE STERILANT FOR
MEDICAL DEVICES
This is a continuation of application Ser. No. 08/565,995, filed on Dec. 1, 1995, which was abandoned upon the filing 5 hereof.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a room temperature antimicrobial composition which includes an ester of formic acid, an oxidizer, performic acid, and water, a premix for making the anti-microbial composition, a method for producing the anti-microbial composition, and a method for sterilizing medical devices utilizing the anti-microbial composition.
2. Background of Related Art
Conventional methods of sterilizing medical devices have significant disadvantages. For example, the steam autoclave works well, but many instruments are sensitive to the high 2Q pressure and temperature required to achieve sterility. Ethylene oxide requires long exposure times in a vacuum, even longer aeration times, and the gas is highly toxic. Glutaraldehyde is a suspected carcinogen and can be corrosive to certain materials. In the field of medical devices which come 2J in contact with a patient's blood stream, care must be taken to sterilize or reprocess these devices with biocompatible anti-microbial compositions.
This is particularly true concerning catheters and blood filters such as dialyzers. Many of the aforementioned ster- 30 ilizing techniques leave residues on the surfaces of the sterilized device which are toxic to the human body and may cause severe adverse patient reactions, such as skin rashes, hemolysis, and the like. Furthermore, if the dialyzer is to be reprocessed for reuse, it is particularly important that the 35 anti-microbial composition be an effective biocide while remaining biocompatible because any residual antimicrobial composition may elute from the dialyzer into the bloodstream of the dialyzed patient, again causing severe adverse patient reaction, which may exacerbate the condi- 40 tion of the patient already in renal failure.
SUMMARY OF THE INVENTION
An object of the present invention is to provide an easy to use room temperature anti-microbial composition. ^
A further object of the present invention is to provide an anti-microbial composition for sterilizing medical devices which overcomes the disadvantages of known methods of sterilizing medical devices.
The invention relates to an anti-microbial composition 50 having improved anti-corrosive properties comprising an ester of formic acid, an oxidizer, performic acid and water.
A preferred embodiment of the invention relates to an anti-microbial composition having improved anti-corrosive properties comprising about 0.01 to about 10 wt. % of an 55 ester of formic acid selected from the group consisting of ethyl formate, methyl formate, propyl formate, or mixtures thereof, about 0.01 to about 10 wt. % of an oxidizer, about 0.001 to about 5 wt. % of performic acid, and up to about 99.98% water. 60
The invention also relates to a premix for making the anti-microbial composition comprising two parts. One part comprises the ester of formic acid and a second part comprises the oxidizer.
The invention further relates to a method making the 65 anti-microbial composition comprising the steps of combining the premix.
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The invention also relates to a method of producing the anti-microbial composition comprising the steps of combining an ester of formic acid with an oxidizer and water.
The invention further relates to a method of sterilizing surfaces comprising contacting the surface with an antimicrobial composition diluted to a working concentration, the anti-microbial composition comprising from about 0.01 to about 10 wt. % of an ester of formic acid selected from the group consisting of ethyl formate, methyl formate, propyl formate, or mixtures thereof, about 0.01 to about 10 wt. % of an oxidizer, about 0.001 to about 5 wt. % of performic acid, and up to about 99.98% water.
A further embodiment of the invention relates to a method of sterilizing blood filters, such as dialyzers used as artificial kidneys, comprising contacting the dialyzers the antimicrobial composition comprising from about 0.01 to about 10 wt. % of an ester of formic acid selected from the group consisting of ethyl formate, methyl formate, propyl formate, or mixtures thereof, about 0.01 to about 10 wt. % of an oxidizer, about 0.001 to about 5 wt. % of performic acid, and up to about 99.98% water. The anti-microbial composition can be diluted to a working concentration by dilution from 1:1 to 1:12 with water.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1. illustrates the sporicidal effects of the antimicrobial composition according to the invention compared to two conventional anti-microbial compositions.
FIG. 2. illustrates the bactericidal effects of the antimicrobial composition according to the invention compared to two conventional anti-microbial compositions.
FIG. 3. illustrates the net mass loss of brass after 24 hours of exposure as measured in Example 2.
FIG. 4. illustrates the concentration of performic acid in hard and deionized water over time as measured in Example 3.
FIG. 5. illustrates the concentration of hydrogen peroxide in hard and deionized water over time as measured in Example 3.
FIG. 6. illustrates the stability of hydrogen peroxide and performic acid in deionized water over time as measured in Example 3.
DETAILED DESCRIPTION OF THE
PREFERRED EMBODIMENTS
The invention relates to an anti-microbial composition having improved anti-corrosive properties comprising an ester of formic acid, an oxidizer, performic acid and water.
Preferably, the anti-microbial composition comprises about 0.01 to about 10 wt. % of the ester of formic acid, about 0.01 to about 10 wt. % of an oxidizer, about 0.001 to about 5 wt. % of performic acid, and up to about 99.98 wt. % water. More preferably, the anti-microbial composition comprises about 2 to about 8 wt. % of the ester of formic acid, about 1 to 10 wt. % of an oxidizer, about 0.001 to about 1 wt. % of performic acid, and up to about 97 wt. % of water.
Preferably, the ester of formic acid is an ester of ethyl formate, methyl formate, propyl formate, or mixtures thereof. More preferably, the ester of formic acid is ethyl formate.
The oxidizer can be any oxidizer that is compatible with a performic acid based anti-microbial composition. Examples of such oxidizers include nonorganic oxidizing substances such as, hydrogen peroxide, sodium
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percarbonate, sodium periodate, sodium persulfate, ammonium persulfate, sodium perborate, sodium peroxide, calcium peroxide, silver (II) oxide, ozone, and chlorine dioxide. The oxidizers also include organic oxidizing substances, for example, diacyl peroxides, such as benzoyl peroxide, ketone 5 peroxides, such as 2, 4-pentanedione peroxide, peroxydicarbonates, such as diisopropyl peroxydicarbonate, peroxyesters, such as t-butylperoxy maleic acid, dialkyl peroxides, such as dicumyl peroxide, hydroperoxides, such as t-butyl hydroperoxide, and peroxyketals, such as 2,2-di 10 (t-butyl peroxy) butane.
Preferably, the oxidizer is hydrogen peroxide. More preferably, the oxidizer is urea hydrogen peroxide.
A preferred anti-microbial composition comprises ethyl formate in an amount of about 3 to about 6 wt. %, urea 15 hydrogen peroxide in an amount of about 1 to about 8 wt. %, and about 0.001 to about 1 wt. % of performic acid.
The anti-microbial composition can also contain additives, such as, corrosion inhibitors and stabilizers. 2Q
Examples of corrosion inhibitors are 1,2,3-Benzotriazole, azimidobenzene and benzene azimide (collectively, COBRATEC 99TM, PMC Specialties Group, Inc.) and the sodium hydroxide reaction products of an aliphatic alcohol and phosphorous pentoxide (VICTAWETTM 35B, Akzo 25 Chemicals, Inc., Chicago, 111). The corrosion inhibiting properties of VICTAWETTM 35B are disclosed in PCT/ US90/01862, entitled "Anticorrosive Microbicide."
The stabilizers include those that stabilize the antimicrobial composition over time, and those that increase the 30 concentration of performic acid, as well as other stabilizers.
The anti-microbial composition can be made in a concentrated form, dry or liquid, to be diluted with water before using.
Purifying the water is not required. When hard tap water 35 is used, surprisingly, the concentration of performic acid in the anti-microbial composition is less likely to decrease or will increase at the expense of the oxidizer, compared to deionized water. This is a significant advantage, because tap water is more readily available and is less expensive than 40 purified or deionized water. In particular, hard water containing calcium acts in this manner.
The invention also relates to a premix for making the anti-microbial composition comprising a first part comprising an ester of formic acid, and a second part comprising the 45 oxidizer. The oxidizer and ester of formic acid include those described above. The anti-microbial composition can be formed by combining the first and second parts with water.
Preferably, the first part comprises an ester of ethyl 5Q formate, methyl formate, propyl formate, or mixtures thereof, and the second part comprises hydrogen peroxide.
Preferably, the amount of the ester of formic acid in the first part and the amount of oxidizer are such that when combined with water the resulting anti-microbial composi- 55 tion comprises about 0.01 to about 10 wt. % of the ester of formic acid, about 0.01 to about 10 wt. % of the oxidizer, about 0.001 to about 5 wt. % of performic acid, and up to about 99.98% water.
Each part of the premix can be in a dry or liquid form. For go example, one or both parts of the premix can be diluted with water. Alternatively, one part can contain all of the required water so that when the other part is added no further water is required, or sufficient water is present in both parts so that when both parts are combined no further water is required. 55
The premix can also contain the above described additives in either or both of the parts.
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The invention further relates to a method of making the anti-microbial composition comprising the steps of combing both parts of the pre-mix. If the pre-mix does not contain the required amount of water, water and the first and second parts can be mixed in any order. Preferably, the antimicrobial composition comprises from about 2 to 5 wt. % ethyl formate, from about 3 to 8 wt. % hydrogen peroxide and from about 87 to 95 wt. % water.
Another embodiment of the invention relates to a method of producing the anti-microbial composition comprising the steps of combining the ester of formic acid with the oxidizer and water.
Preferably, sufficient amounts of water, ester of formic acid, and oxidizer are combined so that the resulting antimicrobial composition comprises about 0.01 to about 10 wt. % of the ester of formic acid, about 0.01 to about 10 wt. % of the oxidizer, about 0.001 to about 5 wt. % of performic acid, and up to about 99.98 wt. % water.
The anti-microbial composition can be used in place of conventional microbicides. The following is a partial list of uses for the anti-microbial composition. The uses of the anti-microbial composition is in no way intended to be limited to this list.
The anti-microbial composition can be used to sterilize the surfaces of medical devices and eating utensils. The anti-microbial composition can also be used to cleanse skin because it is non-toxic and non-irritating to the skin. For example, the anti-microbial composition can be used to cleanse patient pre-operative sites and medical personnel skin, such as hands and arms in presurgical scrubbing.
The anti-microbial composition is particularly useful for reprocessing used catheters which are sensitive to conventional anti-microbial compositions. Preferably, when the anti-microbial composition is used to reprocess used catheters, the anti-microbial composition contains "VICTAWETTM 35b." is believed that the VICTAWETTM acts as a lubricant for the mechanical pump during reprocessing. The reprocessing method disclosed in U.S. Pat. Nos. 4,721,123 and 5,310,524 are incorporated herein.
The anti-microbial composition is also particularly useful for sterilizing filter modules containing filter membranes in various forms, such as hollow fibers. Sterilization of filter modules using the anti-microbial composition of the present invention is particularly useful for reprocessing hollow fiber membrane dialyzers because not only are the dialyzers rendered microbe-free but the anti-microbial composition also removes residual proteinaceous blood components. Hollow fiber filter cartridges sterilized using the antimicrobial composition are suitable for re-use in a medical dialysis setting, such as for artificial kidney.
The invention will be further described by the following non-limiting examples.
EXAMPLE 1
Three tests were performed on samples of an antimicrobial composition according to the invention made by combining 3.8 to 4% by weight of ethyl formate, 4% urea hydrogen peroxide, and the balance water, which will hereinafter be referred to as "Microbicide 1" for notation purposes only. Performic acid was generated in an amount of about 0.001 to about 0.1 wt. %.
The anti-microbial composition was compared to two known microbicides, CIDEXTM 7 (Johnson and Johnson, Medical) and 1% RENALIN® II (Minntech Corporation, published in PCT/US92/05877).
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