CA1210327A

CA1210327A - Hydrogen peroxide composition

Info

Publication number: CA1210327A
Application number: CA000440822A
Authority: CA
Inventors: Beth E. Willcockson; David C. F. Law
Original assignee: Surgikos Inc
Current assignee: Ethicon Inc
Priority date: 1982-11-12
Filing date: 1983-11-09
Publication date: 1986-08-26
Also published as: ZA838440B; ATE35149T1; GR78754B; DE3377066D1; ES527150A0; EP0109279A2; AU2118783A; EP0109279B1; ES8600056A1; EP0109279A3; AU554472B2; US4477438A

Abstract

Hydrogen Peroxide Composition Abstract An antimicrobial composition containing hydrogen peroxide is disclosed. The composition is non-corrosive to surgical instruments and contains 4%-7% hydrogen peroxide, 0.1% to 0.3% of a chelating agent, 0.1% of a water soluble zinc compound, 0.1% to 0.3% of a sodium cocoyl sarcosinate or is fatty acid-based analogs, an anionic surfactant selected from the group consisting of sodium n-decyl diphenylether disulfonate or sodium lauryl sulfate and a buffer system to maintain the pH of the composition in a pH range of from 4 to 6.

Description

3;5~7 H~drogen Peroxide Composition Field of the Invention This invention relates to an improved hydrogen-peroxide-based sterilizing and disinfecting solution which is stabilized to prevent decomposition of hydrogen peroxide and to prevent corrosion damage to medical instruments contacted with the solution.

Background of the Invention It has long been recognized that hydrogen peroxide can be employed as an antimicrobial agent to sterilize ànd disinfect environmental surfaces and surgical instruments.
However, hydrogen peroxide has not been extensively used as an antimicrobial agent for hospital equipment because of its instability and because it tends to corrode surgical instruments. Aqueous solutions of hydrogen peroxide are inherently corrosive to a variety of metals such as iron, nickel, copper! chro~e and their alloys.
Corrosion of these metals when in contact with a hydrogen peroxide solution produces ions which catalyze the decomposition of hydrogen peroxide and accelerate the loss of the antimicrobial activity of the solution. The decomposition of hydrogen peroxide is acco~panied by the release o~ the oxygen which, if allowed to accumulate in a closed container, can create a fire or explosion hazard.
There have been numerous attempts to ~tabilize hydrogen peroxide to prevent its rapid decomposition.

U.S. Patent~ 3,053,634 discloses a composition containing hydrogen peroxide, a chelating agent, an alu~inum compound and a phosphate salt.

J~U-4~
i U.S. Patent 2,961,306 discloses a composition containing 50~/o/80% hydrogen peroxide and 0. 001%-1% 1, 2-diaminocy-clohexane tetraacetic acid.

U.S. Patents 3, 089, 753 and 3,208,825 disclose compo-sitions having pH values of about 3.3 and 2.5, respec-tively, containing hydrogen peroxide, a chelating agent, a tin compound such as Na2SnO3 and a phosphate salt.

U.S. Patent 2,680,674 dislcoses a composition containing hydrogen peroxide and a zinc or cadmium compound such as the sulfate, nitrate or chloride.

Kassem et al disclose the use of ethylenediamine tetraacetic acid to stabilize hydrogen peroxide against the catalytic effects of iron and zinc See Chemical Abstracts 78:164666H and 7~3:164667J.

We have found that the stabilizer systems mentioned in 20 the above-cited references are insufficient to prevent the corrosion o~ surgical instruments or the decompo-sition of hydrogen peroxide when the hydrogen peroxide solution is used as a sterilizing and disinfecting agent.
S~mmarV of the Invention , In accordance wi.th the invention, there is provided an a~ueous disin:~ecting soluti.on having a buffered pH
30 of from 4 to 6.0 and which is not corrosive to surgical instruments~ comprising from 4% to 6% by weight hydrogen peroxide, from 0.1% to 0.3% by weight of an anionic surfactant selected from tbe group con-sisting of sodium lauryl sulfate and sodium n-decyl 35 diphenylether disulfonate, from 0.1% to 0.3% by weight ~2:L~3~7 - 2a -of a sarcosinate surfactant selected from the group consisting of sodium cocoyl sarcosinate and sodium lauryl sarcosinate; 0.1% by weight of a soluble zinc compound selected ~rom the group consisting of zinc sulfate, zinc acetate, zinc nitrate and zinc gluconate and from 0.1% to 0.3% by weight of a nitrogen contain-ing chelating agent selected from the group consisting of N-(hydroxy-ethyl) ethylenediamine triacetic acid, ethylenediamine tetracetic acid and diethylenetriamine pentaacetic acid.

The present invention thus provides a sterilizing and disinfecting solution in which hydrogen peroxide is the active ingredient and in which the solution is stabilized against the decomposition of the hydrogen peroxide and which solution will not excessively cor-rode surgical instruments. The solution has excellent sterilization and disinfecting properties and can be used to sterilize sophisticated medical instruments such as endoscopes without causing excessive damage to such instruments. The present composition contains a number of ingredients ` i CI 3~7 ~

each of which is necessary in the composition to produce the desired result. These ingredients are the followingO

1. Hydrogen Peroxide.

2. A nitrogen-containing chelating agent such as N-(hydroxyethyl)ethylenediamine-triacetic acid (HEEDTA), ethylenediamine-tetraacetic acid (EDTA), or diethylenetriamine-pentaacetic acid (DTPA) or their sodium salts.

3. A water soluble zinc compound such a zinc sulfate, zinc acetate, zinc nitrate or zinc gluconate.

4. A sarcosinate surfactant such as sodium cocoyl sarcosinate or sodium lauryl sarcosinate.

5. An anionic surfactant selected from the group consisting of sodium n-decyl diphenylether disulfonate or sodium lauryl sulfate.

6. A buffer composition such as sodiu~ acetate, sodiu~
phosphate, sodium borate or mixtures thereof to maintain the p~ of the aqueous solution at a level of fro~ pH 4.5 ~5 to p~ S.5.

I Detailed Description of the Invention The compositions of this invention are aqueous solutions containing the following ingredients: (all percentages are by weight based on the total wieght of the solution) ~, .
(1) Hydrogen peroxide (H2O2), in a concentration between 4% and 7~.

` ~ 35 (2) A nitrogen-containing chelating agent such as N-(hydroxyethyl)-ethylenediaminetriacetic acid (HEEDTA), JS~42 32~7 ethylenediaminetetraacetic acid (EDTA), and diethylene-triaminepentaacetic acid (DTPA) or their sodiu~ salts, in a concentration from 0.1% to 0.39%.

(3) A soluble compound containing zinc ions such as zinc sulfate, zinc acetate, zinc nitrate or zinc gluconate in a concentration of about 0.1%. The presence of the zinc in the formulation provides improved corrosion inhibition against copper and nickel and maintains the transparency of the solution. The preferred zinc co~pound is zinc sulfate heptahydrate.

(4) Sodium cocoyl sarcosinate and its fatty acid-based analogs of the structure:
O O
Il ~1 R-C-N-CH2-C-O- Na+

where R is a hydrocarbon chain having hetween 11 and 14 carbon atoms. These are employed at a concentration of 0.1-~ to 0.3~.

~5) An anionic surfactant selected from the group consisting of sodium n-decyl diphenylether disulfonate and sodium lauryl sulfate in a concentration from 0.1~ to 0.3~.

~6) ~ buffer operating in the pH range from 4 to 6, such as sodium acetate, ~odium phosphate and sodium borate.
The buffer concentration range may be 0.5% or bel~w.

It has been found that all of the above-mentioned ingredi-ents are necessary in order to obtain a satisfactory solu-tion with the desired stability, non-corrosiveness and antimicrobial proper~ies.

lSU-4~

A composition containing the above-mentioned ingredients provides excellent antimicrobial activity and does not excessively corrode surgical instruments. The composition can be used at room temperatures and at elevated temperatures, e.g., 40C to 50C. The anti-microbial activity of the composition is enhanced if the composition is employed at an elevated temperature.
At elevated temperatures, the composition will disinfect and sterilize in a shorter time period than at room temperature. However, the composition is an effective disinfecting solution at room temperatures in reasonable time periods~

In addition to the ingredients specified above, the composition of the present invention may also contain optimal inactive ingredients such as a dye, for example FD&C ~ellow No. 5. The present composition may be packaged as a single component with all the ingredients in one container or may be packaged aS a two-component system. As a two-component system, the hydrogen peroxide is mixed with water and placed in one container. The remaining ingredients are placed in a second container with a small amount of water, and the contents of the two containers are thoroughly mixed immediately prior to use. When the two-component ~ystem is used, a small amount o a surfactant, which is a condensate o~ ethylene oxide with propylene glycol and propylene oxide, e.g~ PLURO~IC P104 (trade mark, BASF Wyandotte), may be added to the second container to maintain homogenicity of the ingredients.

The sporicidal test employed in the following Examples is the A.O.A.C. Sporicidal Test as specified in Official Methods of Analysis of the Association of Official Analytical Chemists ~A.O.A.C.~ 13th Edition, 1980 Sections 4.015-4.017. The Use Dilution Test is em-ployed in Sections 4.007-4.011, The Fungicidal Test is employed in J~

03æ~7 Sections 4.018-4.022, and the T~berculocidal Test is el~ployed in Sections 4.048-4.050 of the same publication.

In the Examples, all percentages are weight percent unless otherwise indicated.

Example I

This Example sho~s that the compositions of the present invention have exc~llent antimicrobial properties, and the compositions do not cause corrosion of surgical instruments.

Two solutions containing 6% hydrogen peroxide were prepared according to the formulations set forth in Table lA.

Table lA

~0 Co~positions of Sterilizing/Disinfecting Solutions Ingredients Formulation I Formulation II
(Weight Percent) (Weight Percent~

25 Hydrogen peroxide 6.0 6.0 Ace~ic Acidca. 0.1 ca. 0.1 Zinc sulfate ~7H2O) 0.1 0.1 HEEDTA* 0-3 0-3 Sodium cocoyl sarcosinate 0.3 0.3 30 Sodium lauryl sulfate 0.15 --; Sodium n-decyl diphenylether disulfonate -- 0.15 Water remainder remainder Solution pH S.0 5.0 *N-(hydroxyethyl)ethylenediamine triacetic acid ;

-7-The formulations were tested against various organisms at a temperature of 40C, and the results are shown in Table lB.

Table lB

Failure Rates in AOAC Sporicidal or Exposure Time Use Dilution Tests Organisms Carriers (minutes) Form. I Form. II
,Sporicidal Test _ subtilis porcelain 30 0/60 0/60 spores 45 0/60 0/60 siIk suture 30 1/60 0/60 20C. sporo~enes porcelain 30 2/60 2/60 spores 45 1/60 0/60 siIk suture 30 0~60 0/60 4~ 0/6Q 0/60 ~ Use Dilution Test S. aureus stainless steel 10 1/60 0/60 P. aeruginosa stainless steel 10 0/60 0/60 35_ choler- stainless aesuis steel 10 0/60 0/60 In an AOAC Sporicidal Test, one failure in 60 is not acceptable.

- The Environmental Protection Agency considers a failure rate of 1/60 in a Use Dilution Test as above the minimum requirement of a passing test.

The corrosion properties of the For~ulation I and II solu-tions were tested by immersing a carbon steel scalpel blade, a brass fitting, a "nickel silver" skin closure clip and a pair of chrome-plated scissors in the respec tive solution in a glass container at a temperature of 40C. The results are shown in Table lC. ~"Nickel silver" is an alloy of copper, nickel and zinc.) Table lC

Corrosion/Stability Studies on Hydrogen Peroxide Sterilizing/Disinfecting Solutions at 40C.
~0 Co~m. Available Hydrogen Peroxide F~rmulation I F~rmulation II Solution-After Observations After 6 days After 6 days 3 Hours __ ~5 hydrogen peroxide 6.30~ 6.02%

pH 5.4 5.3 ca. 1.8 3~
precipitate none none heavy ppt.

carbon steel untarnished untarnished untarnished brass untarnished untarnished tarnished nickel silver untarnished untarnished tarnished chrome untarnished untarnished The presence of a precipitate in the solution indicates that the ~etal has been removed from the sa~ples and precipitated from the solution.

Exa~ple 2 A formulation of the present invention containing:
5~ hydrogen peroxide 0~2~ HEEDTA
0.15% sodium n-decyl diphenylether disulfonate (DOWFAX 3B2; trade mark, Dow Chemical Co.) O.3% sodiu~ cocoyl sarcosinate 0.1% ZnSO4 7H2O
water to 100%

The formulation also contained sufficient acetic acid to give a resultant pH of 5.0 and 0.1% of a nonionic surfac-tant which consists of condensates of ethylene oxide with propylene glycol and propylene oxide (PLURONIC P104~.

The formulation was tested against various organisms at 20C. In some tests the formulation was diluted with water in a ratio of 1 part formulation to 2 parts water 25 to determine the effect of the dilution on the activity.
The results are presented in Table 2. The results shown that at a peroxide concentration of 3% (1:2 dilution), the formulation is not effective against certain organisms, i.e., S. aureus and M. tuberculosis.

.: ~

Tabl e 2 Exposure MicroorganisT sTime (Min. )DilutionFailure Rate S. aureusa 10 undiluted 5/30 undiluted 0/60 1:2 44/60 _ aeruginosaa , 20 undiluted 1/60 1 :2 1/60 S. choleraesuisa 20 undiluted 0~60 1 :2 0/60 _ mentagrophytesb 5 undiluted passed undiluted . passe undiluted passed 1: 2 passed 1:2 passed 1: 2 passed _ ~uberculosisC 20 undiluted 0/~0 1 :2 30/80 ~5 The Environmental Protection Agency considered a failure rate o~ 1/60 as a ~Ipass~ for A.O.A.C. Use Dilution Test. ~ .
.
aA.O.A.C. Use Dilutlon Test bA, O u A . C . Fung i c idal Test ~A . O . A . C . Tuberculoc idal Test JSU-4~

Example 3 This Exa~ple shows that the amount of hydrogen peroxide in the formulation may be reduced to 4% without any reduction in sporicidal activity. Formulations were prepared at 5%
and 4% hydrogen peroxide concentrations. In addition to the hydrogen peroxide, the formulations contained:

0.3% HEEDTA
~ O.1% ZnS04-7H20 0~3~ Sodium cocoyl sarcosinate 0.15% Sodiu~ n-decyl diphenylether disulfonate (DOWFAX 3B2) 95% Water The solutions were adjusted to pH 5 with acetic acid or sodium hydroxide.

The solutions were tested against various spores at 40C
with exposure ti~es of 45 ~inutes. The results of the tests are given in Table 3.

Table 3 25 Spores % H22 Carriers Failure Rates B. _ubtilis 5 Suture 0/30 Porcelain 0~30 4 Suture 0/30 Porcelain 0/30 C. sporogenes 5 Suture 0/30 Porcelain o/30 4 Suture 0/30 Porcelain 0/30 ~.2103Z~

Example 4 In order to show the necessity of various ingredients in the present solution, a series of 29 formulations were prepared with some ingredients o~itted or the concentra-tions changed. All of the for~ulations contained 6%
hydrogen peroxide. The composition of the for~ulations is shown in Table 4A. The corrosiveness of the formulations was then determined by immersing metal specimens in the solutions at 40C ~for six days. The metal specimens included a carbon steel scalpel blade, a "nickel silver"
skin closure clip and a copper fitting. A solution is not acceptable if the solution transparency is poor; if there is a heavy precipitate; if the dissol~ed metal is greater than 100 pp~; or, if the metal speci~ens are indicated to be poor. The solutions in which the final pH was above 6 is a result of a high initial p~3 or a high level corrosion of the ~etal and the loss of hydrogen peroxide. The results of the testing is shown in Table 4B.
An exa~ination of the results set forth in Tables 4A and 4B indicates that hydrogen peroxide solutions must contain the surfactants and chelating agent specified herein and be ~aintained at the proper pH in order to obtain the desired non-corrosive properties.

IZ~0~7 Table 4A

Chelating ZnS047H~O Surfactants (% active) Pgent Initial Final No. (%) A B C Type % pH pH

1 .1 .3 .15 .1 HEE~TA .3 5.0 5.0 2 .1 .3 -- .1 HEEDTA .3 5.0 5.2 3 .1 -- .15 .1 HEEDTA .3 5.0 8.0 4 .1 ~ - .1 HEEDTA .3 5.0 8.7 -- .3 .15 .1 HEEDTA .3 5.0 4.6 6 -- .3 .15 .1 -- -- 5.0 4.1 7 .1 .3 .15 .1 HEE~A.1 5.0 5.1

8 .1 .3 .15 .1 HEEDTA .2 5.0 4.9

9 .1 .3 .15 .1 HEEDTA .4 5.0 4.9 .1 .1 .15 .1 HEEDTA .3 5.0 4.9 11 .1 .4 .15 .1 HEE~TA .3 5.0 5.0 12 .1 .3 .15 .1 HEEDTA .3 3.3 5.0 13 .1 .3 .15 .1 HEEDTA .3 4.0 4.2 14 .1 .3 .15 .1 HEE~TA .3 6.0 8.2 .1 .3 .15 .1 HEE~TA .3 7.0 3.1 16 .1 .3 .15 -- HEEDTA .3 5.0 5.0 17 .1 .3 .15 .1 ECTA .1 5.0 5.0 18 .1 .3 .15 .1 EDTA ~2 5.0 5.~
1~ .1 .3 .15 .1 E m A.3 5.0 5.0 .1 .3 .15 .1 EDTA .4 5.0 4.7 , 21 .1 .3 .15 .1 DTPA .1 5.0 4.4 j 22 .1 .3 .15 .1 DIPA .2 5.0 4.9 ' 23 .1 .3 .15 .1 DIPA ,3 5.0 5.2 ; 24 ~1 ~3 ~15 ~1 DPA .4 5.0 7.6 ,1 .3 .15 .1 DPA .5 5.0 7.3 26 ~1 r3 ~15 ~1 DTPA :.3 4.0 4.g 27 .1 .3 .15 ~.1 DTPA .3 4.5 4.8 2~ 3 .15 .1 DTPA .3 5.5 4.5 29 .1 .3 .15 .1 DTPA .3 6.0 4.8 JSU-~2 ~2~

A - Sodiu~ cocyl sarcosinate B - Sodiu~ n-decyl diphenylether disulfonate C - Nonionic surfactant - condensate of ethylene oxide with propylene glycol and propylene oxide.

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~L2~3X~7 Table 4B

Loss of Dissolved H202 Solution Metals(pp~) ~tal No_ % Transparency Color Precipitate Fe Cu Specimens 1 9 fair sl.blue none .4565.1 gocd 2 7 pcor sl.blue none .4065.1 good 3100 fair sl.green heavy .10 103 poor 4100 fair ~ sl.yellow heavy .15 48.3 poor 518 poor colorl~ss none .50 77.7 good 626 poor colorless none .30 54.6 good 7 ~ good colorless none .30 23.1 good ~ 0 fair sl.blue none .40 54.6 good 9 5 fair sl.blue none.50103 good 104 excellent sl.blue none.4050.4 good 1112 poor sl.blue none.5077.7 good 128 good blue none.202,778 poor 136 pcor sl.blue none.60176 good 149 good sl. green heavy.15 109 poor 154 fair sl.green hea~y.10 134 FOor 167 fair sl~blue none.465.1 good 170 good colorless none.25 19 good 1~0 good sl.blue none .20 81 good 192 fair sl.blue none.20109 fair 204 fair sl.blue none.2555 good 210 good sl.blue none.2563 fair 220 good colorless none.25 40 good 230 excellent colorless none.20 25 good 24100 poor blue heavy .lb 380 poor 25100 poor blue hea~y .15 410 Foor 260 good colorless none.25 36 gocd 273 good colorless none~25 44 go3d 2~0 good colorless none .25 40 good 290 good colorless none .25 42 go~d JSU-4~

Claims

The embodiments of the invention, in which an exclusive property or privilege is claimed, are defined as follows:

1. An aqueous disinfecting solution having a buffered pH of from 4 to 6.0 and which is not corrosive to surgical instruments, comprising from 4% to 6% by weight hydrogen peroxide, from 0.1% to 0.3% by weight of an anionic surfactant selected from the group consisting of sodium lauryl sulfate and sodium n-decyl diphenyl-ether disulfonate; from 0.1% to 0.3% by weight of a sarcosinate surfactant selected from the group consist-ing of sodium cocoyl sarcosinate and sodium lauryl sarcosinate; 0.1% by weight of a soluble zinc compound selected from the group consisting of zinc sulfate, zinc acetate, zinc nitrate and zinc gluconate and from 0.1%
to 0.3% by weight of a nitrogen containing chelating agent selected from the group consisting of N-(hydroxy-ethyl) ethylenediamine triacetic acid, ethylenediamine tetracetic acid and diethylenetriamine pentaacetic acid.

2. An aqueous disinfecting solution of Claim 1 in which the anionic surfactant is sodium n-decyl diphenyl ether disulfonate; the sarcosinate surfactant is sodium cocoyl sarcosinate; and, the soluble zinc compound is zinc sulfate, and the chelating agent is N-(hydroxyl-ethyl) ethylenediamine triacetic acid.

3. A process of disinfecting metallic surgical instru-ments without excessively corroding the instruments, comprising contacting said instruments with a solution having a buffered pH of from 4 to 6.0 and comprising from 4% to 6% by weight hydrogen peroxide, from 0.1%
to 0.3% by weight of an anionic surfactant selected from the group consisting of sodium lauryl sulfate and sodium n-decyl diphenylether disulfonate; from 0.1% to 0.3% by weight of a sarcosinate surfactant selected from the group consisting of sodium cocoyl sarcosinate and sodium lauryl sarcosinate; 0.1% by weight of a soluble zinc compound selected from the group consist-ing of zinc sulfate, zinc acetate, zinc nitrate and zinc gluconate and from 0.1% to 0.3% by weight of a nitrogen containing chelating agent selected from the group consisting of N-(hydroxy-ethyl) ethylenediamine triace-tic acid, ethylenediamine tetracetic acid and diethyl-enetriamine pentaacetic acid.

4. The process of Claim 3 in which the anionic surfactant is sodium n-decyl diphenylether disulfonate;
the sarcosinate surfactant is sodium cocoyl sarcosinate;
and, the soluble zinc compound is zinc sulfate, and the chelating agent is N-(hydroxylethyl) ethylene-diamine triacetic acid.