CA1198972A

CA1198972A - Indicator for detecting residual ethylene oxide

Info

Publication number: CA1198972A
Application number: CA000398378A
Authority: CA
Inventors: Masanori Hamano; Siro Takeuchi; Ichiro Inoue
Original assignee: Ekika Carbon Dioxide Co Ltd
Current assignee: Ekika Carbon Dioxide Co Ltd
Priority date: 1981-03-17
Filing date: 1982-03-15
Publication date: 1986-01-07
Also published as: DE3264620D1; EP0060723B1; JPS57151854A; US4678640A; EP0060723B2; EP0060723A1; AU530145B2; JPS6140344B2; AU8156582A

Abstract

TITLE OF THE INVENTION:
INDICATOR FOR DETECTING RESIDUAL ETHYLENE OXIDE

ABSTRACT OF THE DISCLOSURE:
An indicator for detecting residual ethylene oxide comprising a substrate impregnated with a solution of 4-(4-nitrobenzyl)pyridine and an envelope of the substrate which is at least partially transparent and has low permeability to gaseous ethylene oxide is provided, the envelope being preferably made of a transparent plastic film. With the indicator, an amount of ethylene oxide remaining in various medical instruments, etc. may be estimated by the naked eye since the color of the indicator changes step by step in the course of the release of residual ethylene oxide.

Description

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This invention relates to all inclicator which enables to estimate with the na~ed eye an amount of gaseous ethylene o~ide (hereinafter referred to as "EOG") remainlng in medical instruments or sanitary goods sterili2ed with EOG
by the colour or the color-change of the indicator.
Sterilization of medical instr~ents or sanitary goods is carried out by EOG alone, a mixture of EOG and chlorofluorohydrocarbon or a mi~ture of EOG and carbon dioxide (CO2). On the other hand, since toxicity of EOG is fairly high, sterilization with EOG is frequently accompanied by various harmful influences, for instance, chemical burns, injuries of the skin and mucous membranes and hemolysis, which have attracted the world-wide attention.
Regarding the injuries on living bodies by the residual EOG in the objects sterilized with EOG as importance, Food and Drus Administration (FDA) of ~he United States regulates the acceptable concentration of residual EOG to léss than 25 ppm in the articles to be embedded in living bodies and to less than 250 ppm in the articles to be contacted with the outer side of living bodies~
As a method for quantitative analysis of the residual EOG, gas chromatography and colorimetric analysis are used at present, and both methods require expensive apparatus for analysis and skilled technicians for manipulating the apparatus. In addition, it ta~es a considerably much -time to obtain the analytical results. Consequently, at present the amount oE res:icl~lal F:OC. in the sterili~ecl objects is only estimated while referring to the data obtained by organizations speci~ied in analysis or published in scientific or medical literatures.

However, between these cases and practical cases, there e~ist many differences regarding the conditions of sterilizations, the rnate-rials of the objects to be sterilized and the packing conditions of the objects. AS the result, the courses oE release of EOG are different. Accordingly, it is quite inaccurate to judge the amount of residual EOG based on these data.
Under these situations, in the manufacturers of medical instruments and the material supplying centers in hospitals, there are strong demands for the method and apparatus for estimating instantly and easily the amount of residual EOG in the sterili~ed objects, however such demands have not hitherto been fulfilled.
It is an object of the invention to provide an indi-cator by which the amount of residual EOG can be estimated with the naked eye.
The indicator of the invention comprises a substrate impregnated with a solution o~ 4~ nitrobenzyl)pyridine (hereinafter referred to as NBP), namely, a color-changing site, and an envelope which encloses the substrate therein and has a low permeability to EOG.
The invention will be explained in detail while referring to the drawings.

O~ the drawings, Fig. 1 is a plane view of an indicator o the invention. Flg. 2 is a cross sec~ional view of a flake-like indicator of the invention. Fig. 3 is a cross sectional view of an another flake-like indicator of the invention. Fig. 4 is a cross sectional view of a still another indicator of the invention. Fig. 5 is a cross sectional view of a tablet-like indicator of the invention. Fig. 6 shows diagrams illustrating respectively the relationship between the concentration of residual EOG and the course of release of EOG
from sterilized materials at 25C with the colour change of the indicator of the invention.
The substrate 1 of the indicator of the lnvention is a sheet of paper impregnated with a solution of NBP at a concen-tration of 0.5 to 5~ by weight, preferably 2 to 3~ by weight in an organic solvent such as ethanol, isopropyl alcohol, ethyl acetate, acetone, methyl ethyl ketone and the like, and thereafter dried, the paper being selec~ed from materials easily im~egnat-ed with the solution, preferably being synthetic paper, blotting paper or filter paper.
The envelope 2 which encloses the substrate 1 is at least partially transparent so that the colour-change of the substrate 1 can be observed by the naked eye, and the permeabili-t:y of the envelope to EOG should be substantially low, preferably not more than 200 ml/100 inch2/mil/24 hr at 25C under the atmospheric pressure and 50~ R.H. to CO2 measured according to ~STM D 1434-63.

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~ t is unnecessary to have the envelope 2 closely adhered to the substrate 1, and it is required tha-t the envelope

2 encloses perfectly the substrate 1 to prevent the invasion of air from outside, for instance, as a sealed pouch.
~ ransparent and heat-sealable plastic films may be used as the material for the envelope ~. Such a film may be a single-layer film 3 ~as in Fig. 2) and may be a composite film 4, 5 (as in Fig. 3). As the single-layer film 3, a polyvinyl alcohol film or a nylon film is preferably utilized with a prefe:c-able thickness of 5 to 40 microns. The composite film for use a, the envelope 2 comprises an outer layer ~ having low permeability to EOG and an inner layer having high permeability to EOG
and heat-sealability. As the material for the outer layer 4, polyester, nylon, polyvinyl alcohol, polyvinylidene chloride, polyvinyl fluoride or cellophane is preferable with the preferable thickness of 5 to 40 microns. As the material for the inner layer 5, polyethylene or polypropylene is preferable, and the thickness of the inner layer may be even a little thicker than that of the outer layer.
In addition, as another envelope fulfilling the above-mentioned conditions, a composite material as shown in Fig. 4 may be used, which is manufactured by adhering a plastic film 6 having low permeability to EOG onto a base plate 7 such as a metal foil, for example aluminum foil, which is impermeable to EOG while putting the substrate 1 between ~989~;2 the plastic Ei]m 6 and the base E~late ~. Nanuely, the plastic ~ilm fi contclcts to one side o~ t-he substrate :l, ancl the base plate 7 contacts to the otheI- slde of the substrate 1.
Naturally, Ln this case, as the plastic ~ilm 6, either the above-mentioned single film or the composite film may be utilized.
~he fonn of the indicator for detectinc3 resi~ual F,OG
of the invention may be a flake-like as shown in Figs. 1 to ~, or a tablet-like as shown in Fig. 5. The envelope of the tablet--like indicator may be a single- or a composlte film.
The color of the indieator of the invention changes step-wise as follows;
light blue -~ blue -~ dark blue -~ grey -~ brown -~
light brown ~ yellow in the course of release of EOG, and the time required for cha}l-Jing into each color is the same if the conditions of sterilization and release of EOG are the same. Accordingly, when the relationship between the amount of residual EOG
measured by gas chromatography or the like and the time required for the indicator of the invention to change into each color is established in each material of medical instruments sterilized under the general sterilization conditions, the amount of residual EOG may be visually estimated by placing the indicator of the invention toaether with the object to be sterilized. Namely,by the indicator of the invention, it may be indirectly judged ~e~ r the con~f~n'ratjor of residllal F:~;G in the ohject: ha.5 ~:~9~9~

come to be lower than the predetermined value or the regulatecl value by FDA. It is known that the release rate of EOG from a steri:liæed object is very different according to the conditions of sterilization, the ma!l:erials and its s-tates of the object including the package thereof to be sterili~ed and the conditions under which the sterili~ed object is left. However, if the conditions of sterili~ation and the materials of objects to be sterilized have been predetermined, the amount of residual EOG in the objects after sterili~ation can be estimated by observing the color change of the indicator of the invention as is shown in the following E~amples.
The invention will be further illustrated more in detai1 while re~erring to the following non-limiting Examples. It will be evident to those skilled in the art that variations can be made without departing f-om the s?irit and the scope of the in~Jention as defined in the claims which follow -this specification.
EXA*IPLE 1:
Onto a sheet of filter paper of 10 mm in diameter and 0.5 mm in -thickness, 0.05 ml of a 2 % by weight acetone solution of NBP was dropped, and after drying the sheet in open air, the dried sheet was packaged by heat-sealing in a composite film (60 x 20 mm) comprising a polyester film (permeability to CO2 of 50 ml/100 inch2/mil/24hr) of 12 microns in thickness as the outer layer and a cast polypropylene fi.lm of 40 microns in thickness as the inner laver to prepare an indicator of the invention ~ 6 --7~

shown in .~`i.CJ. 3.
After introducin~J the prepared indicator alone into a sterilizer, the indicator was treated with a gaseous mixture consisting of 30~ by voluine OL- EOG and 70~ by volume of CO~
at 50C and the concentration of EOG of 500 mg~litre Eor 2 hours, and then removed from he sterilizer to be left stand in a room at 25C.
A-t the time when the sterilization of the indlcator was over, it was colourless, however, as the time passed by, it showed the fol].owing colour change as is shown in Table l:

Table 1 Time in 0 0.25 0.5 1 1.5 3 Colour - light biue dark grey brown light blue blue brown Letter of a b c d e f Fig. 6 EX~MPLE 2:

The indicator prepared as in Example 1 was packed into a sterilizing package made of a plastic film and a synthetic film together with each of the following materials or medical instruments such as polyethylene, polystyrene, polypropylene, polycarbonate, ABS, polyacetal, 6-nylon, 6,6-nylon, plasticized polyvinylchloride, latex-rubber, butadiene.--rubber a.nd si3.icon*--rllb~e.r an~3 the.se packages were treated . -- 7 -397~

under the same conclitic-}l dS i.ll ~`~alllple 1. After sterilization, the packclgc~ were removec~ r-rom tlle sterili~er ancl t~as lekt in a room at 25C, alld t:he-collcentra-t:ion oE xesiclual ~OG in the ma'eria~
was determined by gas chromatocJraphy as the time passed by, while the color change of tne indicators were observed.
The colour change of the indicator was the same as in E~ample 1 as shown in Fig. 6, wherein the letter from a to f corresponds to each colour from light blue to ligh-t brown respectively.
As seen from Fig. 6, the course of release of EOG
from the material was classified ln three groups, namely, the first group of late~-rubber, butadiene-rubber and silicone-rubber shown as (1) in Fig. 6 from which EOG was easily released, -the second group o polyethylene and plasticized polyvinyl chloride shown as ~2) in Fig. 6 from which EOG was modera-tely easily released, and the third group of 6,6-nylon, 6-nylon, polycarbonate, polystyrene, polypropylene, ABS and polyacetal from which EOG was difficultly released.
In the material from which EOG was most difficultly released in each of the three groups, namely butadiene rubber in the first group, polyethylene in the second group and ABS
in the third group, the colours of the indicator of the lnvention corresponding to the upper limit of the residual EOG in the regulated values of FDA were shown in Table 2.

', ~9~3~72 I`clble 2 ! Grou~less than 250 ppm less than 25 ppm First light blue blue Second grey brown Third dark blue light brown EXAMPLE 3:
After the same indicator as in Example 1 and each of -the same medical materials as in Example 2 were subjected,to the same conditions of sterili~ation, the indicator and the medlcal materials were transrerred into an airator kept at 50C with an air ven.ilation rate of 500 litres/min. and the colour change of the indicator was observed.
According to the results, the course of release of EOG
could be classified into three groups, however, the time required for the concentration o r residual EOG to be the predetermined value was about one fifth of the time in Example 2 with the same pattenl of colour-change of the indicator appearing within the equally shortened time.

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Claims

The embodiments of the invention in which an exclu-sive property or privilege is claimed are defined as follows:

1. An indicator for estimating concentrations of ethylene oxide remaining in medical instruments or sanitary goods in or after aeration following sterilization of said instruments or goods with ethylene oxide comprising:
(a) a substrate formed by impregnating a paper body with a solution consisting of about 0.5-5% by weight of 4-(4-nitrobenzyl)pyridine in an organic solvent and removing said solvent; and (b) an envelope enclosing said substrate, said envelope comprising a transparent, heat-sealable plastic film of single layer type or composite layer type having a low permeability to ethylene oxide and a permeability to carbon dioxide of not more than about 200 ml/100 in2/mil/24 hours at 25°C under 1 atmosphere and at 50%
relative humidity measured according to ASTM D 1434-63, said substrate sequentially changing color stepwise following the exposure of the indicator to ethylene oxide gas, with the proviso that the color change of said substrate during the aeration is controlled by said envelope having a low permeability to ethylene oxide.

2. The indicator of Claim 1, wherein the plastic film is made of polyvinyl alcohol or nylon.

3. The indicator of Claim 1, wherein the plastic film comprises a composite film comprising an outer layer having low permeability to gaseous ethylene oxide and an inner layer having heat-sealability and high permeability to gaseous ethylene oxide.

4. The indicator of Claim 3, wherein the outer layer is formed from a material selected from the group consisting of polyester, nylon, polyvinyl alcohol, polyvinyl-idene chloride and polyvinyl fluoride.

5. The indicator of Claim 3, wherein the inner layer comprises polyethylene or polypropylene.

6. The indicator of Claim 3, wherein the composite film comprises a polyester film as an outer layer and a poly-propylene film as an inner layer.

7. The indicator of Claim 1, wherein the envelope comprises a base plate made of metal foil and a plastic film having low permeability to gaseous ethylene oxide, the substrate being enclosed therebetween.

8. The indicator of Claim 1, wherein the paper is selected from the group consisting of filter paper, synthetic paper and blotting paper.

9. The indicator of Claim 1, wherein the substrate is in the form of a strip, flake or tablet.