JP2003102811A - Indicator for plasma sterilization and packaging material for sterilization - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an indicator for plasma sterilization capable of clearly judging whether plasma sterilization treatment is applied to a substance to be sterilized, markedly changed in hue, irreversible and increased in discoloration speed at the time of display, and a packaging material for sterilization forming a display part using the indicator for plasma sterilization. SOLUTION: The indicator for plasma sterilization contains at least one compound (A) selected from the group consisting of an adsorption indicator and a chelate titration/metal indicator and an organometal compound (B). Preferably the component (A) is preferably hematoxyline, Mordant Blue 29, Eriochrome Black T, Xylenol Orange, 1-(2-pyridylazo)-2-naphthol (PAN), or the like.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a sterilization indicator using a chemical indicator useful for hydrogen peroxide plasma sterilization treatment, and an object to be treated for plasma sterilization treatment which is provided with a display portion comprising the sterilization indicator. The present invention relates to a sterilization packaging material for storing.

[0002]

2. Description of the Related Art Various sterilizing means have been used for disposable or reusable medical devices, food containers and the like. Typical examples are ethylene oxide gas (EOG) sterilization, Examples include autoclave high-pressure high-temperature steam sterilization, plasma sterilization, and the like.
For example, as a sterilization method carried out in a hospital or the like, an object to be sterilized such as a scalpel or a syringe is put in a packaging bag having at least a gas-permeable region in which bacteria cannot pass, and after sealing, Sterilization is performed by such a method, and the sterilized instrument is stored in this packaging bag until it is used for surgery or the like, and is opened and used when it is used for surgery or treatment. In this case, it is useful from the viewpoint of accident prevention, etc. to attach a label for easily judging whether or not the instrument sealed in the packaging material has been sterilized. The display portion is formed using an ink having an indicating function, which discolors irreversibly when sterilized.

As an example of such an ink, a coloring material such as a diazonium salt compound which is used as a thermosensitive recording material and a thermosensitive microcapsule are included as a colorant which senses a temperature and serves as an indicator of steam sterilization. Coloring materials, etc., that develop color when the temperature of the microcapsules is impaired when they reach a predetermined temperature, are commercially available products such as Nescos I ・ C (S) manufactured by ISC Center (Sakura Crepas). -25B, for high-pressure steam sterilization), inks used for thermo labels and steam integrator cards manufactured by NOF Giken Kogyo Co., Ltd. For example, a composition having a disperse dye having a (AN = NB) structure described in JP-A No. 5-1252 can be used as a material that can be detected by EOG.

Among these sterilization treatments, there is little concern that it will affect the medical instrument which is the object to be sterilized. Therefore, recently, a hydrogen peroxide plasma sterilization method and an apparatus therefor have been proposed and actually used. Yes (Tokuhei 2-622)
61 and 7-22693). This sterilization method is
In summary, the product to be sterilized is exposed to hydrogen peroxide vapor under reduced pressure in an airtight container and then a hydrogen peroxide plasma is generated. This method is very useful in that not only high sterilization efficiency is obtained, but also hydrogen peroxide is converted into water and oxygen which are completely harmless. Examples of the display composition suitable for such plasma sterilization treatment include:
Triphenylmethane dyes, cyanine dyes described in JP-A-11-178904, JP-A-11-3798.
A technique of using the pH indicator described in JP-A-8 as a color-changing dye has been proposed. These display components contain dyes that are discolored or discolored by the oxidizing property of the gas with strong oxidizing power used for plasma sterilization, but the discoloration speed is slow,
Short-time plasma sterilization causes problems such as insufficient discoloration, insufficient light resistance, and undesired discoloration due to handling under white light or daylight, which is not preferable in practice. It was Therefore, the use of a pH indicator whose hue changes with pH as an indicator with a fast discoloration rate has been investigated.However, since this discoloration reaction is reversible, a sterilization bag having such an indicator can be used after sterilization. However, there is a problem in that the hue changes depending on the storage environment, it is unclear whether or not the sterilization treatment is completed, and the stability is poor.

[0005]

SUMMARY OF THE INVENTION Therefore, the object of the present invention is to clearly determine whether or not the object to be sterilized is subjected to plasma sterilization, in which the change in hue is remarkable and irreversible. It is an object of the present invention to provide a sterilization packaging material having a plasma sterilization indicator and a display section using the plasma sterilization indicator having a fast discoloration speed.

[0006]

As a result of studies, the present inventors have found that the above problems can be solved by using a specific organometallic compound, and have completed the present invention.

That is, the plasma sterilization indicator of the present invention contains (A) one or more compounds selected from the group consisting of an adsorption indicator and a chelate titration / metal indicator, and (B) an organometallic compound. It is characterized by One or more compounds selected from the group consisting of (A) adsorption indicator and chelate titration / metal indicator used herein are hematoxylin, modant blue 29, eriochrome black T, xylenol orange, 1- (2-pyridylazo. ) -2-Naphthol (PAN) is preferred. Further, the sterilization packaging material of the present invention according to claim 3 is a sterilization packaging material, at least a part of which is made of a gas-permeable base material, and which can store an object to be sterilized for plasma sterilization treatment. , (A) adsorption indicator, chelate titration / metal indicator, at least one compound selected from the group, and (B) an organometallic compound. It is characterized by

Since the plasma sterilization indicator of the present invention uses an adsorption indicator, a chelate titration / metal indicator as a color-changing compound, there is almost no risk of discoloration during ordinary handling under white light or daylight. ,
The product formed by the reaction of the indicator and the coexisting organometallic compound is p due to hydrogen peroxide in a specific pH range.
It changes to a distinctly different hue due to changes in H and strong oxidizing power of plasma treatment, and since the color change is irreversible, it is suitable as a chemical indicator, and non-sterile substances such as medical devices and food containers are hydrogen peroxide. Even after a lapse of a certain time after receiving the plasma sterilization treatment, it is possible to clearly determine whether or not such treatment has been performed.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention is described in detail below.
The plasma sterilization indicator of the present invention comprises (A) one or more compounds selected from the group consisting of an adsorption indicator and a chelate titration / metal indicator, and (B) an organometallic compound.

First, (A) adsorption indicator, chelate titration
One or more compounds selected from the group consisting of metal indicators will be described. The adsorption indicator that can be used in the present invention is not particularly limited, and any indicator that is discolored by being adsorbed by colloidal particles that are generally used for detecting metal ions can be appropriately used. Adsorption indicators that can be used in the present invention include, for example, Congo red, phenol red,
Methyl red, bromocresol purple, bromophenol blue, titanium yellow, eosin, fluorescein, dichlorofluorescein, dibromofluorescein, aluminone, alizarin, curcumin and the like can be mentioned.

The chelate titration / metal indicator that can be used in the present invention is an organic dye (a dye compound having a proton capable of substituting for a metal ion in the molecule) which changes color by forming a complex ion with a metal ion, and a metal ion. It is selected from compounds having a polydentate ligand capable of binding to a chelate compound. Chelate titration indicators are polyaminocarboxylic acids,
It may be any of water-soluble compounds represented by oxycarboxylic acids and condensed phosphates, and sparingly soluble compounds represented by dimethylglyoxime, oxine, dithizone and the like. Specific examples of the chelate titration / metal indicator usable in the present invention include, for example, Tyrone, Modant Blue 29,
Eriochrome Black T, Xylenol Orange, Isalin Red S, N-benzoyl-N-phenylhydroxylamine, 5-sulfosalicylic acid dihydrate, sulfosalicylic acid dihydrate, 1- (2-pyridylazo) -2-
Naphthol (hereinafter referred to as PAN), murexide,
Examples thereof include hematoxylin, ethylenediaminetetraacetic acid disodium dihydrogen dihydrate (EDTA), phthalein complexone, dimethylglyoxime, oxine, dithizone, and methylthymol blue.

Among the above compounds, preferred compounds for the present invention include hematoxylin, modant blue 29, eriochrome black T, xylenol orange, PAN and the like. Among them, they are easily available and change in hue before and after sterilization. Hematoxylin is preferable from the viewpoint of easy detection. These compounds may be used alone or in combination of two or more depending on the purpose. The above (A) in the indicator for plasma sterilization of the present invention
The content of at least one compound selected from the group consisting of an adsorption indicator and a chelate titration / metal indicator is appropriately determined in relation to the (B) organometallic compound described in detail later, but in general, it is solid. The amount is about 0.2 to 10.0% by weight, preferably 0.5 to 5.0% by weight. If the content is less than 0.2% by weight, the light resistance is reduced, or the color of the display portion after sterilization and discoloration is light, and the visibility tends to be low. If the content exceeds 10.0% by weight. When adjusting the coating liquid for forming the display portion, undissolved substances tend to be easily generated, which is not preferable.

Next, the (B) organometallic compound will be described. The (B) organometallic compound preferably used in the present invention is a hue which reacts with one or more compounds selected from the group consisting of the above (A) adsorption indicator and chelate titration / metal indicator in the presence of an acid. Is an aluminum chelate compound such as aluminum ethylacetoacetate, a titanium chelate compound such as diisopropoxybis (acetylacetonato) titanium, and acetylacetone tributoxyzirconium.

Specific examples of the organometallic compound which can be preferably used in the present invention include aluminum ethyl acetoacetate, aluminum tris (ethyl acetoacetate), aluminum tris (acetyl acetonate) and aluminum bisethyl acetoacetate. Aluminum chelate compounds such as monoacetylacetonate, diisopropoxybis (acetylacetonato) titanium, isopropoxy (2-ethyl-1,3-hexanediolato) titanium, diisopropoxybis (triethanolaminato) titanium, Acetyl titanium chelate compounds such as di (2-ethylhexoxy) bis (2-ethyl-1,3-hexanediolato) titanium, di-n-butoxybis (triethanolaminato) titanium, and tetraacetylacetonate titanium Cetone tributoxy zirconium and the like, preferably selected from aluminum chelate compounds having a chelating ability, titanium chelate compounds, among them, aluminum ethyl acetoacetate diisopropylate, diisopropoxybis (acetylacetonato) Titanium is preferred. These compounds may be used alone or in combination of two or more. The content of these compounds is
Generally, the solid content is about 0.2 to 5.0% by weight, preferably 0.5 to 3.0% by weight. If the content is less than 0.2% by weight, the hue before plasma sterilization becomes unstable, and if it exceeds 5.0% by weight, the hue before plasma sterilization changes with time or the ink for an indicator after preparation is changed. Any of these is not preferred because problems such as increased viscosity of the ink are likely to occur in the stability of the ink.

The indicator for plasma sterilization of the present invention containing each of the compounds (A) and (B) has irreversible color change due to a change in pH and strong oxidizing power, and thus has preferable characteristics as an indicator. . Speaking of specific discoloration, for example, when phenol red is used as the component (A) and aluminum ethyl acetoacetate diisopropylate is used as the component (B), the hue before sterilization is yellowish red, and the color after sterilization is red. Discolor. Further, when the same component (B) is used, when Eriochrome Black T is used as the component (A), the color changes from gray to yellow, and when hematoxylin is used, the color changes from dark brown to yellow. All of these can detect discoloration at a glance.

In the sterilization indicator of the present invention, in addition to the above-mentioned essential components, other compounds that are usually used for forming an ink for display can be used in combination. The sterilization indicator of the present invention preferably contains a binder. The binder serves as a carrier when the indicator is used as the display portion of the packaging material. The binder is not particularly limited, and for example, a synthetic resin or the like usually used for preparing printing ink can be appropriately selected and used. In the indicator of the present invention, from the viewpoint of stability as a composition, an alkali-resistant polymeric material such as polyamide or ethylcellulose-based binder is preferable, but damages from alkaline components can be prevented by preparing other additives. Therefore, it does not necessarily have to be alkali resistant. Therefore, considering the discoloration speed and stability of the dye, for example, nitrified cotton or the like can be preferably used as the binder. The type and amount of the binder may be appropriately selected according to the characteristics as a sterilization indicator, the material of the packaging material or container to be applied, the required durability, etc.
It is generally about 5 to 30% by weight.

In the plasma sterilization indicator of the present invention, in addition to the above-mentioned components, known additives such as a plasticizer, a dispersant, a stabilizer and a thickener are added to improve durability and handleability. It can be contained as appropriate. Particularly, from the viewpoint of improving light resistance, it is preferable that the indicator for plasma sterilization of the present invention contains an ultraviolet absorber. As the ultraviolet absorber, any type can be used as long as it is a commonly used one in this field as long as it does not adversely affect the achievement of the object of the present invention. Specifically, for example, a triazine-based compound, a benzotriazole-based compound, a hindered amine-based compound, etc. are preferable. As such a compound having an ultraviolet ray blocking effect, as a commercially available product, various compounds known by the trademark of Tinuvin of Ciba-Geigy can be mentioned. The ultraviolet absorber may be used alone or in combination of two or more kinds of compounds, but it is also effective to use a plurality of kinds of ultraviolet absorbers having different characteristics.

The indicator for plasma sterilization of the present invention is a composition that discolors by plasma sterilization treatment. However, when the hue of the indicator after discoloration is thin, in order to ensure visibility, the hue of the dye main component is not impaired. In addition, dyes and pigments that do not lose color or change color by sterilization can be added.

The plasma sterilization indicator of the present invention comprises:
Each of the above components can be dissolved in a suitable solvent, applied to a region where labeling is required, dried and used. The solvent is selected in consideration of the solubility of the anthraquinone dye and other components, but considering the solubility of the binder resin, the stability of the dye and the efficiency of drying during printing, ethanol, methanol, propylene. Glycol, ethyl acetate, isopropanol, n-propanol, toluene and the like are preferable.

Next, the packaging material for sterilization of the present invention will be described. This wrapping material has a sterilizable region, at least a part of which is made of a gas-permeable base material, and can be configured by arbitrarily selecting a known sheet-like material having a required strength. . Examples of the gas-permeable base material include paper, porous film, woven cloth and non-woven cloth, and among these, paper or non-woven cloth is preferable. However, it is more preferable to use a material that does not adsorb H ₂ O ₂ used for sterilization. A sterilizable region, that is, at least a region made of paper or non-woven fabric having a permeability in a range in which a gas (gas) as an active ingredient is permeated and a bacterium is not permeated in the plasma sterilization treatment applied to the present invention is at least. Must have some. Although it is possible to configure all of the packaging materials with such a sterilizable material, from the viewpoint of cost, strength, and visibility of the contents, one uses a gas permeable material such as paper or nonwoven fabric,
On the other hand, it is also a preferred embodiment to use a transparent synthetic resin sheet or the like. For example, a gas-permeable paper or non-woven fabric sheet on one side and a transparent synthetic resin sheet on the other side are used in combination and two sheets are formed into a bag shape, which is easy to manufacture and the contents can be visually confirmed. Sex and strength are secured.

As described above, the packaging material for sterilization of the present invention has a structure in which two sheets on the front and back are laminated and peelable adhesive portions are provided in the vicinity of both side edges, and at least one of the sheets has a display portion by the indicator. It is formed by providing. This packaging material is processed into an arbitrary shape, such as a bag shape or a roll shape, and supplied.

The display portion is usually formed by dissolving at least the above-mentioned plasma sterilization indicator composition in a suitable solvent on a sheet constituting a packaging material, coating and drying. A surface protection layer for protecting the indicator can be provided on the indicator thus formed. If the surface protective layer is transparent or translucent so that hydrogen peroxide vapor used for plasma sterilization treatment or plasma derived from hydrogen peroxide can be transmitted and the color change of the dye can be seen through, It can also be formed from various components. Among them, from the viewpoint of affinity with the display part, it contains a binder constituting the composition forming the indicator as a film-forming component, and a UV absorber, a water-repellent component for imparting water resistance, and an abrasion resistance. It is preferably formed from a composition containing a sexual component, specifically a wax component such as polyethylene wax. The surface protective layer of such a display portion can also be formed by dissolving it in a solvent and applying the same as in the formation of the display portion.

The display portion of the sterilized packaging material is usually formed on the surface of a gas-permeable paper or non-woven sheet which constitutes a part of the packaging material. When the other constituent material of the packaging material is a transparent sheet through which the inside can be seen, the indicator layer is formed inside the gas-permeable paper or nonwoven sheet or inside the transparent resin sheet (that is, the packaging material is formed). It can be formed inside the bag body).

The composition which constitutes the indicator is homogeneously mixed using known kneading methods such as those used in the preparation of printing inks, which are then applied to the sheet material which constitutes the packaging material. To form an indicator. Examples of the coating method include known printing methods such as offset printing, flexographic printing and gravure printing. The same method can be used when the surface protective layer is formed on the display portion. The coating amount of the display part is not particularly limited and can be arbitrarily selected as long as the display can be visually recognized, but generally 0.2 to 20 g / m ²
It is about the range, and preferably in the range of 1 to 10 g / m ² . If the coating amount is too small, the visibility after sterilization will be poor,
If the amount is too large, the scratch resistance during transportation and storage tends to decrease. Further, the coating amount of the surface protective layer provided as desired is preferably in the range of 1 to 10 g / m ² .

[0025]

EXAMPLES The present invention will be described in detail below with reference to specific examples, but the present invention is not limited thereto. In the following examples, "%" indicates "% by weight" unless otherwise specified.

Example 1 The following components constituting the indicator for plasma sterilization were mixed and stirred until they were homogeneous to prepare a composition for forming an indicator. (Indicator composition for plasma sterilization) -Hematoxylin 1.0% by weight-Diisopropoxybis (acetylacetonato) titanium 1.0% by weight-Varnish (Safele: trade name, manufactured by T & K TOKA) 80.5% by weight- Methanol 15.0% by weight ・ Ultraviolet absorber 2.5% by weight (Tinuvin 400: trade name, manufactured by Ciba Geigy)

The indicator composition was applied to the sheet surface of the high density polyethylene nonwoven fabric by a gravure method using a gravure roll so that the applied amount after drying would be 10 g / m ² . The hue of the display was dark brown.

(Examples 2 to 10) In the indicator composition for plasma sterilization, instead of hematoxylin,
A composition for forming an indicator portion was prepared in the same manner as in Example 1 except that each adsorption indicator and chelate titration / metal indicator shown in Table 1 below were used to form a display portion. The hue of the display section is also shown in Table 1 below.

[0029]

[Table 1]

(Evaluation of Indicator for Plasma Sterilization) 1. Display performance The low-temperature plasma sterilization system [STE
RRAD-100 (trademark) manufactured by Johnson & Johnson Medical Co., Ltd.] and sterilized for 75 minutes, and the change in hue of the display was observed. 2. Discoloration speed Immediately after forming the display portion on the non-woven fabric sheet, it is put into a low temperature plasma sterilization system [STERRAD-100 (trademark) Johnson & Johnson Medical Co., Ltd.] and treated with hydrogen peroxide for 1 minute. The operation was stopped and the change in the hue of the display was visually observed. A sample that was completely discolored was evaluated as ◯, and a sample that could not be visually detected was evaluated as x.

3. Sterilization performance and display performance of sterilization packaging material The above-mentioned non-woven fabric sheet was used on one side and a transparent polyester / low density polyethylene laminated film was used on the other side, and three sides were heat-sealed to prepare a sterilization packaging bag. A biological indicator (BI) is placed in this sterilization bag and sealed, and a low temperature plasma sterilization system [STERRAD-100 (trademark) Johnson & Johnson Medical Co., Ltd.]
Manufactured] and sterilized for 75 minutes. The change in hue of the display portion after sterilization was observed. The results are shown in Table 2 below.
In addition, the biological indicator is aseptically taken out, seeded in a sterilized TSB medium, and cultured at 35 ° C for 7 days,
The presence or absence of growth of bacteria was visually confirmed. The results are also shown in Table 1 above.

As is clear from Table 1, it was confirmed that the plasma sterilization indicator of the present invention rapidly discolors due to the plasma sterilization treatment and has a high discoloration speed, and exhibits an excellent display function. Furthermore, the display portion after the discoloration for which the display performance was examined was stored for 75 minutes in an alkaline atmosphere. However, in any of Examples 1 to 10, no change in the hue of the indicator was observed, so that the discoloration was pH. It was confirmed to be irreversible, not dependent on. It was also confirmed that even in the case of a sterilized packaging material, there was no problem in the display function and no problem in the plasma sterilization treatment effect.

(Examples 11 to 20) Examples 1 to 10
In the same manner as in Example 1, except that aluminum ethyl acetoacetate diisopropylate was used in place of the organometallic compound diisopropoxybis (acetylacetonato) titanium in the sterilization indicator composition used in 1. The nonwoven fabric sheets and sterilized packaging materials of Examples 11 to 20 were obtained and evaluated in the same manner as in Example 1. The results of the evaluation are the same as those in Examples 1 to 10, and even when the organometallic compound is changed, generally the same hue is obtained,
It was confirmed that good display performance and sterilization performance were achieved in all cases.

(Example 21) A non-woven sheet and a sterilized packaging material were obtained in the same manner as in Example 1 except that ethanol was used in place of the solvent methanol in the composition for display part of the above-mentioned example 1. Then, the same evaluation as in Example 1 was performed. The hue before discoloration was gray, but the hue after sterilization was almost the same as in Example 1, and it was confirmed that similar hue, display performance, and sterilization performance were obtained even when the solvent was changed. .

[0035]

According to the present invention, it is possible to clearly determine whether or not the plasma sterilization process has been performed on the object to be sterilized, and it is possible to provide an indicator for plasma sterilization in which the discoloration speed at the time of display is fast. Further, since the packaging material for sterilization of the present invention has a display portion using the indicator for plasma sterilization, it is possible to clearly determine whether or not the sterilization target has been subjected to plasma sterilization.

Continued front page    F term (reference) 3E064 BA22 BB03 EA19 HA10 HB10                       HQ10                 3E067 AA11 AB01 AB83 BA12A                       BB01A BB06A CA03 EA04                       EE01 EE35 FA01 FB12 FC01                       GC06                 4C058 AA01 BB06 DD15 KK06

Claims (3)

[Claims] 1. (A) one or more compounds selected from the group consisting of adsorption indicators and chelate titration / metal indicators;
(B) An organometallic compound-containing indicator for plasma sterilization. 2. The (A) adsorption indicator, chelate titration /
One or more compounds selected from the group consisting of metal indicators are compounds selected from hematoxylin, modant blue 29, eriochrome black T, xylenol orange, 1- (2-pyridylazo) -2-naphthol (PAN). The indicator for plasma sterilization according to claim 1, wherein 3. A sterilization packaging material, at least a part of which is composed of a gas-permeable base material, capable of containing an object to be sterilized for plasma sterilization treatment, comprising: (A) an adsorption indicator, a chelate titration metal. A packaging material for sterilization, comprising a display part formed of an indicator for plasma sterilization containing (B) an organometallic compound, and one or more compounds selected from the group consisting of indicators.