# Patent

## Title
Sterilization method

## Abstract

A method of sterilizing a material, said method comprising the steps of: a) providing a sterilizing composition comprising (i) peracetic acid and (ii) a stabilizer selected from the group consisting of citric acid, isocitric acid, aconitic acid and propane-1,2,3-tricarboxylic acid; b) introducing such sterilizing composition into a hot gaseous stream to produce a peracetic acid vapor; and c) contacting such peracetic acid vapor with the material to be sterilized. The use of such an organic acid stabilizer results in an unexpected reduction in the amount of residue deposited on the heating surface employed to vaporize the sterilizing composition.

## Background
CROSS REFERENCE TO RELATED APPLICATIONS
This application is a Continuation of U.S. application Ser. No.: 13/796,439, filed Mar. 12, 2013, which claims the benefit of the filing date of U.S. Provisional Application No. 61/610,007 which was filed Mar. 13, 2012. The entire content of these applications is hereby incorporated by reference herein.


FIELD OF THE INVENTION
The present invention is directed to a method of sterilizing a material, said method comprising the steps of: a) providing a sterilizing composition comprising (i) peracetic acid and (ii) a stabilizer selected from the group consisting of citric acid, isocitric acid, aconitic acid and proprane-1,2,3-tricarboxylic acid; b) introducing such sterilizing composition into a hot gaseous stream to produce a peracetic acid vapor: and c) contacting such peracetic acid vapor with the material to be sterilized. The use of such an organic acid stabilizer results in an unexpected reduction in the amount of residue deposited on the heating surface employed to vaporize the sterilizing mixture.
BACKGROUND OF THE INVENTION
The necessity of sterilizing surfaces for health and sanitary purposes has long been recognized. Effective sterilization processes are needed for a variety of purposes including aseptic packaging, medical instrument sterilization, biocidal vector environmental remediation, fumigation, vessel sterilization, food stuff treatments, and others.
Among the compounds employed as a sterilizer for such uses is peracetic acid (“PAA”), also called peroxyacetic acid. In order to prolong the shelf-life of PAA compositions, stabilizers are typically added. These stabilizers act as chelators for dissolved metal cations that can disrupt the peroxide bond.
The use of vapor phase peracetic acid to sterilize surfaces is described in U.S. Patent Application 2010/0196197. This publication discloses the use of peracetic acid stabilized with phosphoric acid or acid stabilizers such as Dequest 2010, 1-Hydroxyethylidene-1,1,-diphosphonic acid. While such process is effective to sterilize a variety of different surfaces, it has been found that when such phosphonic acid stabilizers are employed the surface of the heating element used to vaporize the peracetic acid solution tends to become covered with residue over a period of time. This build-up of residue requires that such surface be periodically cleaned, a process which can be time consuming and expensive.
It would therefore be highly desirable to possess a method for using vapor phase peroxyacetic acid as a sterilizing agent which method did not require the relatively frequent cleaning of the heating surfaces of the equipment employed.
While PAA compositions comprising citric acid have been disclosed in the past, such compositions have been employed in liquid aqueous sanitizing applications only. Thus, for example, WO 2008/079999 discloses sterilizing compositions comprised of PAA, citric acid or a salt thereof, and salicylic acid or a salt thereof, which compositions are applied topically to the surfaces to be disinfected employing solution spray systems or the like. Somewhat similarly, U.S. Pat. No. 6,117,457 and European Patent Application 720814 both disclose the use of citric acid in aqueous PAA generation systems; either as a pH regulator in fish ponds or as a means of providing extended PAA generation, respectively.
However, it has now been unexpectedly found that when PAA stabilized with an organic acid such as citric acid is employed in vapor phase sterilization, the buildup of residue on heating surfaces is considerably less than when a phosphonic acid stabilizer is employed. This result is particularly unexpected in view of the showing that aqueous solutions of citric acid (in the absence of PAA) result in the undesirable buildup of residue on heating surfaces.
SUMMARY OF THE INVENTION
The present invention is directed to a method of sterilizing a material, said method comprising the steps of: a) providing a sterilizing composition comprising (i) peracetic acid and (ii) a stabilizer selected from the group consisting of citric acid, isocitric acid, aconitic acid and propane-1,2,3-tricarboxylic acid; b) introducing such sterilizing composition into a hot gaseous stream to produce a peracetic acid vapor; and c) contacting such peracetic acid vapor with the material to be sterilized.
This method permits the effective vapor sterilization of a material without the need for frequently disassembling the apparatus employed in order to remove the buildup of residue which occurs upon the heating surfaces of such apparatus. Accordingly, a wide variety of materials may be rapidly and economically sterilized employing the method of this invention.


DETAILED DESCRIPTION OF THE INVENTION
The present invention is directed to a method of sterilizing a material, said, method comprising the steps of: a) providing a sterilizing composition comprising (i) peracetic acid and (ii) a stabilizer selected from the group consisting of citric acid, isocitric acid, aconitic acid and propane-1,2,3-tricarboxylic acid: b) introducing such sterilizing composition into a hot gaseous stream to produce a peracetic acid vapor; and c) contacting such peracetic acid vapor with the material to be sterilized.
As is employed herein, the term vapor means a state in which the peracetic acid is substantially entirely in the gaseous form. This is in contrast to mist or fog, both of which contain a significant proportion of liquid droplets suspended in the air. Unlike the use of a mist or fog, it has been found that the use of peracetic acid in vapor form provides excellent sterilization of materials without the concomitant formation of water droplets on the material surface.
Peracetic acid is typically employed in the form of an aqueous equilibrium mixture of acetic acid, hydrogen peroxide and peracetic acid. The weight ratios of these components may vary greatly, depending upon the particular grade of PAA employed. Among the grades of PAA which may be employed are those having weight ratios of PAA:hydrogen peroxide:acetic acid of from 12-18:21-24:5-20; 15:10:36; 5:23:10; and 35:10:15.
The stabilizer employed in the PAA sterilizing composition is selected from the group consisting of citric acid, isocitric acid, aconitic acid and propane-1,2,3tricarboxylic acid. Preferably, such stabilizer is citric acid.
Typically, the stabilizer is employed in an amount sufficient to stabilize the PAA for at least three months. Preferably, the stabilizer is present at a concentration sufficient to stabilize the PAA for a period of at least six months.
In general, such stabilizer will typically be present in an amount of between about 0.75% and about 1.5%; preferably of between about 0.9% and 1.25%; and more preferably of between about 1.0% and about 1.2%; all such percentages being by weight, based upon the total weight of the PAA composition.
The composition employed in the process of this invention may further comprise sequestriants such as dipicolinic acid, as well as other ingredients such as mineral acid catalysts (sulfuric, nitric, or phosphoric acids); surfactants such as anionic laurylates, sorbitans and their respective esters, i.e. polyethylene sorbitan monolaurylates; and short chain fatty esters (C6-C12) forming mixed peracids in solution.
In addition, the compositions employed in the process of this invention may further comprise one or more additional oxidants selected from the group consisting of chloroperbenzoic acid, perheptanoic acid, peroctanoic acid, perdecanoic acid, performic acid, percitric acid, perglycolic acid, perlactic acid and perbenzoic acid.
In the practice of the process of this invention, the peracetic acid sterilizing composition is preferably diluted, prior to its introduction into the heated gas stream, by the addition of high quality water (deionized water with ≧2 MOhm resistivity or ≦0.5 μSiemens conductivity), to a concentration of less than about 10,000 parts per million (ppm) of PAA, preferably to a concentration of less than about 4,000 ppm PAA.
The heated gas stream is typically sterile air, although other gases such as nitrogen, CO2, or inert noble gas carriers may also be employed. Such gas stream is typically heated to a temperature of at least about 300° C., preferably to a minimal temperature of about 250° C. and can be in excess of 350° C. providing it can be cooled sufficiently for application. It then is typically cooled to between about 80° C. and about 120° C. prior to the introduction of the peracetic acid solution. The heated gas stream at the point of peracetic acid introduction should have a temperature of at least 5° C. higher than the dew point of peracetic acid (ca. 46.5°-49.9° C.); i.e., of at least about 55° C., in order to ensure that the peracetic acid is converted into a vapor rather than a fog or mist.
The peracetic acid may be introduced into the heated air stream by any means well known to one of skill in the art. One preferred method is by direct injection of a solution.
The peracetic acid vapor is then contacted with the material to be sterilized for a period sufficient to kill the contaminants of concern. This time period will vary according to variables such as the concentration of the peracetic acid vapor employed; the nature of the surface of the material to be sterilized; the particular contaminants to be sterilized; the concentration of the contaminants to be sterilized; and the like. Typically, such contact will maintained for a period of between about 15 and about 40 minutes.
A wide variety of materials may be sterilized employing the method of this invention, including hard surfaces of metals, plastics, polymers, and elastomers.
The present method may be used to sterilize materials contaminated with those bacteria typically controlled by peracetic acid in the liquid form. These include bacteria and spores of the genus Bacillus using B. thuringiensis and B. atrophaeus as surrogates for more pathogenic species (forms), such as C. botulinum as well as more typical genera of bacteria, fungi, and viruses and protozoans often controlled by PAA such as (but not limited to): Staphlococcus, Enterococcus, Salmonella, Campylobacter, Pseudomonas, Candida, Rhizopus, Mucor, Influenza, Bacilli, etc.
The following Examples are presented to offer further illustration of the present invention, but are not intended to limit the scope of the invention in any manner whatsoever.
Example 1
In order to demonstrate the stabilizing effect of citric acid on PAA compositions, varying amounts of citric acid were added to concentrated PAA compositions, which compositions were stored at room temperature. Periodically, at the times indicated in Tables 1-4 below, samples of such compositions were analyzed for their peracetic acid (PAA); hydrogen peroxide (H2O2); and acetic acid (AA) contents (in percent by weight); and their Active Oxygen Recovery percentage (AO Rec) was calculated. The data presented in such Tables indicates that citric acid alone can stabilize PAA compositions for extended periods of more than 3 or 6 months.







TABLE 1







0.91% Citric Acid











Days After Addition
PAA %
H2O2 %
AA %
AO Rec %














—
0.8438
15.0778
49.4288
88.94


1 
2.8207
14.4139
47.1477
90.21


2 
4.8579
13.7938
45.1340
91.89


3
6.8554
13.1946
43.4419
93.58


4
8.1230
12.7316
42.2202
94.18


8
12.1365
11.4882
38.1054
97.35


9
11.8892
11.2862
37.8752
95.55


10
12.8904
11.1100
37.6596
97.12


11
13.3851
11.0106
36.8579
97.82


14
15.3285
10.6744
35.9054
100.89


15
14.4656
10.6141
35.8921
98.32


16
14.7712
10.5483
36.6383
98.72


17
15.4082
10.5003
36.1812
100.09


18
15.0226
10.4909
36.6624
99.04


21
15.3530
10.3126
35.4124
98.87


28
16.1285
10.1703
34.9291
100.04


36
16.0191
10.0980
34.7712
99.35


43
16.6856
10.0932
34.0215
101.03


77
15.7208
9.8166
35.5012
96.96


95
15.8097
9.8772
35.7577
97.54


133
15.4084
9.7041
35.5974
95.51


162
14.2637
9.6438
36.2839
92.21


197
14.8616
9.5118
35.3907
92.99


228
14.5168
9.4222
35.9890
91.59


260
13.9939
9.2273
36.6908
89.12


285
13.8226
9.1102
36.1968
88.01


314
14.2674
9.0070
36.6037
88.56


344
13.3877
8.9848
36.4208
86.17


378
13.5115
8.8263
36.9739
85.57


403
13.0327
8.6849
37.7293
83.53
















TABLE 2







1.00% Citric Acid











Days After Addition
PAA %
H2O2 %
AA %
AO Rec %














—
0.8688
17.1802
47.8195
101.08


1 
2.8990
15.7369
45.8501
98.00


2 
5.1241
14.8095
43.8144
98.39


3
7.1400
13.9885
42.6610
98.86


4
8.4730
13.3357
41.1202
98.53


8
12.0610
11.7606
37.6254
98.70


9
12.8241
11.5194
37.3773
99.28


10
13.1537
11.3034
37.6218
98.88


11
13.3192
11.1213
37.4239
98.26


14
14.8345
10.7323
36.7059
99.92


15
14.8165
10.6578
36.3016
99.45


16
14.8555
10.5471
35.7440
98.91


17
14.9233
10.5083
36.4307
98.86


18
15.1771
10.4201
35.2700
99.01


21
15.5752
10.2907
35.7839
99.29


28
16.0195
10.1210
34.7292
99.45


36
15.4584
10.0619
35.0277
97.67


43
15.9848
10.0408
34.6613
98.90


77
15.6363
9.8988
35.8995
97.19


95
15.4839
9.8409
34.7765
96.46


133
15.0663
9.6691
36.3532
94.40


162
14.8545
9.6176
36.6276
93.56


197
14.8315
9.477
35.6838
92.69


228
14.4704
9.3548
36.0888
91.06


260
15.0582
9.2067
35.5108
91.72


285
14.3021
9.0621
36.2798
88.94


314
14.197
8.956
37.3694
88.06


344
13.9533
8.8917
36.8442
87.06


378
13.1943
8.7715
37.5735
84.42


403
12.9297
8.6296
37.1723
92.82
















TABLE 3







1.15% Citric Acid











Days After Addition
PAA %
H2O2 %
AA %
AO Rec %














—
0.9493
14.9203
49.7722
88.31


1 
2.7103
14.0927
47.8537
88.08


2 
4.8674
13.5088
45.8163
90.27


3
6.7840
12.8510
44.2981
91.42


4
8.0746
12.4248
42.6000
92.29


8
11.8005
11.2592
38.8622
95.17


9
12.7506
11.1215
37.9775
96.82


10
13.0775
10.9839
37.7389
96.87


11
13.7122
10.8617
38.0374
97.80


14
14.4521
10.6744
36.8023
98.63


15
14.7832
10.5997
36.0188
99.05


16
14.9035
10.5517
35.5883
99.09


17
14.9890
10.5392
35.5743
99.23


18
15.1184
10.4180
35.4307
98.87


21
15.7941
10.3115
35.4520
100.00


28
16.1877
10.1272
34.7089
99.95


36
15.0727
10.0837
34.9070
96.83


43
15.8094
10.0461
35.0496
98.51


77
15.5986
9.8953
35.6593
97.10


95
15.5719
9.8333
35.9455
96.67


133
16.0577
9.6417
34.8538
96.82


162
15.1268
9.5816
36.0882
94.08


197
15.7167
9.5183
34.8321
95.23


228
13.9662
9.3003
36.2149
89.47


260
13.4297
9.1271
36.3155
87.09


285
14.3050
9.0125
36.4291
88.69


314
13.5222
8.9160
36.6740
86.12


344
13.8437
8.8414
37.2805
86.51


378
13.0769
8.7360
47.0423
83.93


403
12.9157
8.5879
37.2918
82.67
















TABLE 4







1.24% Citric Acid











Days After Addition 
PAA %
H2O2 %
AA %
AO Rec %














—
0.7259
12.9350
51.4255 
76.31


1 
2.6857
13.1213
48.8097
82.42


2 
4.7080
12.8994
46.6388 
86.35


3
6.6668
12.4803
45.0566
88.98


4
8.1618
12.0665
43.2028
90.45


8
12.3648
11.1363
39.9843
95.91


9
12.5204
10.9715
38.9763
95.37


10
13.1867
10.8514
38.4447
96.39


11
13.8380
10.7723
37.6754
97.61 


14
14.3456
10.5460
36.8458
97.62


15
14.6369
10.5380
36.0910
98.32


16
14.7992
10.4648
35.8426
98.43


17
14.9864
10.4538
35.7862
98.74


18
15.3825
10.4189
36.6292
99.55


21
15.3706
10.2649
35.4215
98.64 


28
15.8088
10.1306
35.0317
98.99 


36
15.8843
10.0424
35.1196
98.68


43
15.9236
10.0629
35.2217
98.90


77
15.6937
9.8773
35.6800
97.24


95
15.7823
9.7861
36.1936
96.94


133
15.1511
9.6406
35.6101
94.48 


162
15.0181
9.5280
36.4564
94.39


197
15.5437
9.3555
35.0428
93.85


228
14.1509
9.2284
36.2681
89.53


260
14.9844
9.0772
35.7010
90.81


285
14.3708
8.9362
36.5596
88.42


314
14.1109
8.7402
36.4426
86.62 


344
13.9393
8.7677
36.9396
86.34


378
13.4533
8.6343
37.2074
84.32 


403
13.3214
8.5447
38.2168
83.46









Example 2
In order to determine the amount of residue buildup produced by vaporization, various solutions were prepared by blending the following ingredients:

    Samples A1, A2 and A3: 250 ppm citric acid in deionized water
    Sample B1: 4000 ppm PAA+about 24 ppm Dequest 2010
    Samples C1 and C2: 4000 ppm PAA+250 ppm citric acid


The PAA employed had a PAA:hydrqgen peroxide:acetic acid weight ratio of about 15:10:36.
An initial portion of the sample to be tested was placed into a 50 mL burette suspended over a 100 mL beaker placed on a Corning Stirrer/Hotplate. The hotplate was heated to 180° C. and the stopcock on the burette opened such that the solution was added drop wise for vaporization. The burette was refilled before it ran out of solution. The hotplate was shut off and the beaker allowed to return to room temperature. Once it had cooled to room temperature, the beaker was reweighed to determine the amount of residue present. The results observed and the calculated amount of residue (mg/mL) are summarized in Table 5 below.










TABLE 5





Sample 
Residue (mg) 
Volume of Solution (mL)
Mg/mL of Residue


















A1
20
92.5
0.22


A2 
31
109.9
0.28


A3 
27
117
0.23


B1
131
94.3
1.39


C1
0
121.6
0.00


C2
3
92
0.03









The above results show that the method of the present invention (exemplified in Samples C1 and C2) produces considerably less residue of the heating surface than does a PAA composition of equal concentration which is stabilized using a phosphonate stabilizer. This result is completely unexpected in view of the showing that the vaporization of citric acid in deionized water results in the formation of a much more residue than does the vaporization of a composition comprising an equal amount of citric acid in a PAA solution.

## Claims

1. A composition comprising peracetic acid vapor and a stabilizer selected from the group consisting of citric acid, isocitric acid, aconitic acid, propane-1,2,3-tricarboxylic acid, maleic acid, malic acid, fumaric acid, nitric acid and phosphoric acid.

2. The composition of claim 1, wherein the peracetic acid concentration is less than about 4,000 ppm to less than about 10,000 ppm and the stabilizer concentration is less than about 250 ppm.

3. The composition of claim 1, wherein the peracetic acid concentration is less than about 10,000 ppm.

4. The composition of claim 1, wherein the peracetic acid concentration is less than about 4000 ppm.

5. The composition of claim 1, wherein the peracetic concentration is less than about 700 ppm.

6. The composition of claim 1, wherein the stabilizer is citric acid.

7. The composition of claim 1, wherein the stabilizer concentration is less than about 120 ppm.

8. The composition of claim 1, further comprising an oxidant selected from the group consisting of chloroperbenzoic acid, perheptanoic acid, peroctanoic acid, perdecanoic acid, performic acid, percitric acid, perglycolic acid, perlactic acid and perbenzoic acid.

9. The composition of claim 1, further comprising a sequestrant, a mineral acid catalyst, a surfactant or a short chain fatty ester.

10. The composition of claim 1, made by the step of introducing a sterilizing composition comprising peracetic acid and a stabilizer selected from the group consisting of citric acid, isocitric acid, aconitic acid, propane-1,2,3-tricarboxylic acid, maleic acid, malic acid, fumaric acid, nitric acid and phosphoric acid into a hot gaseous stream.

11. The composition of claim 10, wherein the concentration of peracetic acid in the sterilizing composition is from about 15 to about 17 weight percent of the sterilizing composition and the concentration of the stabilizer is from about 0.75 to about 1.5 weight percent of the sterilizing composition.

12. The composition of claim 10, wherein the peracetic acid is in the form of an aqueous equilibrium composition having a peracetic acid: hydrogen peroxide: acetic acid weight ratio selected from the group consisting of 12-18: 21-24:5-20; 15:10:36; 5:23:10; 21-23:6-10:33-36; and 35:10:15.

13. The composition of claim 10, wherein the hot gaseous stream is heated to a temperature of above about 250° C. prior to the introduction of the sterilizing composition.

14. The composition of claim 13, wherein the hot gaseous stream is heated to a temperature above about 250° C. and is then cooled to a temperature of between about 80° C. and about 120° C. prior to the introduction of the sterilizing composition.

15. The composition of claim 10, wherein the temperature of the hot gaseous stream is at least about 5° C. higher than the dew point of peracetic acid.