WO2004110897A1

WO2004110897A1 - Method for indicating degeneration of content in package being substituted with carbon dioxide after break of seal of package

Info

Publication number: WO2004110897A1
Application number: PCT/JP2004/008861
Authority: WO
Inventors: Kouhei Yuyama; Hiroshi Honda; Minoru Oka; Hidekatsu Shoji
Original assignee: Otsuka Pharmaceutical Factory, Inc.
Priority date: 2003-06-17
Filing date: 2004-06-17
Publication date: 2004-12-23

Abstract

A method for indicating the time until the degeneration of a content of a package having been substituted with carbon dioxide at a time after the break of the seal of the package, which comprises arranging a carbon dioxide indicator having a pH indicator covered with a carbon dioxide permeable material together with the content in the above package and indicating the time of the degeneration of the content by the change of the color of said pH indicator.

Description

Specification

Method of indicating the deterioration of the contents inside the carbon dioxide replacement package after opening the package

According to the present invention, the time period during which the contents of food, beverages, pharmaceuticals, and the like packed in a carbon dioxide gas replaced package become unusable due to deterioration after opening the package is indicated by the color tone of the carbon dioxide gas contained in the package. About the method.

Background technology

A common method of storing foods, beverages, pharmaceuticals, etc. for a long time is gas replacement packaging. In this gas replacement packaging, the contents are packaged with a packaging material having excellent gas barrier properties, and the inside of the package is replaced with, for example, a mixed gas of nitrogen gas and carbon dioxide gas. Taking the bicarbonate-containing drug solution as a medical preparation as an example, the carbon dioxide replacement packaging will be described in detail. The bicarbonate-containing drug solution is contained in a drug solution container, and the contents are packaged. It is packaged with carbon dioxide replacement in the body. That is, the medical solution container is placed in a package, and the package is sealed and packaged in a carbon dioxide atmosphere. The bicarbonate constituting the bicarbonate-containing chemical solution is a chemical having a property of decomposing to release carbon dioxide gas and losing its medicinal effect. According to the carbon dioxide replacement packaging, the generation of carbon dioxide from the bicarbonate is stopped when the equilibrium with the carbon dioxide concentration in the package is reached, and thus the decomposition of the chemical solution and the reduction of the medicinal effect can be prevented.

In such gas replacement packaging, if pinholes or seal failures occur due to defects in the packaging material itself, failure when enclosing the contents, or impacts during the transportation process such as distribution, these can be detected. It is known that carbon dioxide can be detected overnight.

For example, Japanese Patent Application Laid-Open No. 64-69951 proposes a carbon dioxide gas detection indicator in which a base material is impregnated with a phenolphthalein reagent and covered with a carbon dioxide-permeable transparent plastic.

The present inventors have also studied and developed various pH indicators, carbon dioxide gas indicators, pinhole detection agents, and the like using similar pH indicators (for example, see WO 97/48365). Pamphlet, JP-A-11-197215, JP-A-2000- 279486, JP-A-2000-281147, JP-A-2000-308669, WO 01/44385, JP-A-2003-72857, JP-A-2003-93474, etc.). Hereinafter, these are collectively referred to as “carbon dioxide indicator”.

In any of these carbon dioxide gas indicators, carbon dioxide gas is generated from a chemical solution such as a bicarbonate-containing chemical solution packaged by gas replacement in the package body due to an unexpected accident such as the occurrence of a pinhole in the package body. Is detected by the color change of the pH indicator.

The purpose of this use of carbon dioxide gas is to detect the outflow of carbon dioxide gas from the package in a state in which the package is replaced with carbon dioxide gas. Once the carbon dioxide gas flows out due to the occurrence of pinholes and the like, as a result, the carbon dioxide gas indicator that has detected the alteration of the contents no longer changes the color tone of the pH indicator after opening the package. In addition, the carbon dioxide indicator, which has been confirmed that there is no change in color tone and that the content can be used safely, is used when the package is opened and the content is put to practical use, for example, for medical use. It has been usually discarded as it has already achieved its original purpose, such as pinhole detection.

On the other hand, a chemical solution container containing a bicarbonate-containing chemical solution is usually formed of a material permeable to carbon dioxide gas, but after opening the gas barrier packaging, rapid release of carbon dioxide gas from the container is performed. Does not happen. Therefore, it has been considered that the release of carbon dioxide gas from the inside of the container can be neglected and the reduction of the medicinal effect can be neglected while the medical solution contained in the container is used for general medical use.

However, when the above bicarbonate-containing drug solution is used for actual medical use, for example, hemodialysis or peritoneal dialysis, the application time may be as long as several hours. Also, in actual medical practice, for example, a large number of packages containing a bicarbonate-containing drug solution may be used at the same time, and in such a case, all the packages are opened at once in advance and the One by one may be used sequentially. Furthermore, after opening the package, the remaining chemical solution may be used again without using up the chemical solution all at once. In each of these cases, the drug solution container containing the bicarbonate-containing drug solution is left in the atmosphere for a considerable time after opening the package, during which time the release of carbon dioxide from the drug solution, In addition, deterioration of the drug solution (reduction or loss of drug efficacy due to decomposition) due to this is inevitable. Hereinafter, the term “alteration” used for a drug solution refers to a state in which such a desired drug effect cannot be exhibited.

Even if the use of a carbon dioxide indicator could detect the deterioration of the drug solution during storage (before opening the package), unless there is a means to know the deterioration of the drug solution after opening, medical accidents in each of the above cases, etc. The danger of occurrence cannot be sufficiently prevented.

However, no consideration is given to examining the alteration of the bicarbonate-containing solution contained in the drug solution container after opening the package, and, of course, such alteration of the drug solution after opening is not considered. No studies have been done on how to examine it.

Disclosure of the invention

The present invention has been made in view of the above-mentioned circumstances, and a first object of the present invention is to remove the deterioration of the contents due to the release of carbon dioxide from the contents after opening the package that has been replaced with carbon dioxide. And to provide a way to do so.

A second object of the present invention is to provide a carbon dioxide gas indicator used for a method of checking the quality of contents after opening the above-mentioned package, and a package using the same. The present inventors have the idea that the carbon dioxide gas indicator that can detect the concentration of carbon dioxide previously developed can be used to achieve the object of the present invention. As a result of intensive studies based on this idea, the present invention has been completed.

The present invention provides a method for confirming the deterioration of the contents in the carbon dioxide replacement package after opening the package shown in the following items, and a carbon dioxide gas indicator, a package, and a carbon dioxide detection ink composition used in the method. And so on.

Item 1. This is a method of indicating the deterioration of the contents replaced with carbon dioxide gas after opening the package, and the carbon dioxide gas indicator in which the ρΗ indicator is coated with a carbon dioxide gas permeable member together with the contents inside the package. A method of indicating the time when the contents of the package are opened after opening the package by changing the color tone of the cinnamate gas.

Item 2. The method according to Item 1, wherein the color tone change of the carbon dioxide indicator is caused by emission of carbon dioxide from the indicator.

Item 3. The carbon dioxide gas permeable member has a carbon dioxide gas permeability of 50 to 20,000 mL / m ² · 24 hours, and the carbon dioxide gas is released from the carbon dioxide indicator by adjusting the carbon dioxide gas permeability. Control the speed to change the content after opening the package Item 4. The method according to Item 2 or Item 3, wherein the color tone of the carbon dioxide gas is changed with the time when the color tone changes.

Item 4. The male according to any one of Items "!" To "3", wherein the content is a bicarbonate-containing chemical solution contained in a plastic drug solution container having carbon dioxide gas permeability.

Item 5. The method according to Item 4, wherein the drug solution container is a multi-chamber container having two or more storage chambers each capable of independently storing a drug solution, and having a partition wall capable of communicating between adjacent chambers.

Item 6. The bicarbonate-containing chemical is selected from the group consisting of a solution containing sodium bicarbonate and sodium chloride contained in the ^first compartment, and a magnesium sulfate and magnesium chloride contained in the second compartment. Item 6. The method according to Item 5, which is a solution containing at least one of glucose and glucose.

Item 7. The bicarbonate-containing chemical solution is a solution containing sodium bicarbonate and citric acid contained in the first chamber, and a solution containing oxydartathione contained in the second chamber. The described method.

Item 8. The method according to any one of Items 1 to 7, wherein the pH indicator is in any one form selected from the group consisting of a liquid, a solid, and a printed layer.

Item 9. The method according to Item 8, wherein the printing layer is formed on a support using a carbon dioxide sensing ink composition containing a pH indicator, a binder and a solvent.

Item 10. The method according to Item 9, wherein the supporter is a support sheet that can be attached to a part of the chemical solution container or the chemical solution container.

Item 11. The method according to Item 9 or 10, wherein the ink composition for detecting carbon dioxide gas further comprises at least one selected from the group consisting of a water absorbing agent and an alkaline substance.

Item 12. A carbon dioxide indicator used in the method according to any one of Items 1 to 11. Item 13. A package that can indicate deterioration of the content of the carbon dioxide gas-displaced package after opening the package, obtained by using the carbon dioxide indicator described in Item 12.

Item 13. An ink composition for detecting carbon dioxide, comprising a pH indicator, a binder, and a solvent, for the carbon dioxide gas indicator according to Item 14.

Item 15. Use of the method according to Item 1 in Item 1 of Carbon dioxide gassing described in Item 12. Item 16. Use of the ink composition for detecting carbon dioxide gas described in Item 14. for producing the carbon dioxide gas indicator according to Item 12. (1) Carbon dioxide indicator

The carbon dioxide indicator used in the method of the present invention is obtained by coating a pH indicator with a carbon dioxide permeable member. The structure of this product shall be the same as those described in each of the above-mentioned patent publications, on the premise that the time required for the contents to be altered can be indicated by the change in the color tone of the pH indicator. Can be done. The descriptions of these publications are incorporated herein by reference.

An example of a preferable carbon dioxide gas indicator is an indicator including a pH indicator and a surface layer covering the indicator, and the surface layer is composed of a carbon dioxide permeable member and is necessary for changing the color tone of the pH indicator. One that can control the time required for an appropriate amount of carbon dioxide gas to permeate through the surface layer in accordance with the time required for the contents to be altered.

The indicator is preferably a liquid, a solid, or a printed layer containing a pH indicator. That is, the pH indicator has any one form selected from the group consisting of a liquid material, a solid, and a printed layer. The indicator, which is a liquid or a solid, may be housed in a bag of a carbon dioxide permeable member constituting the surface layer, for example, to form a carbon dioxide gas. The indicator, which is a printed layer, can be formed on a suitable support using a carbon dioxide gas detecting ink composition containing a pH indicator. This printed layer can then be coated with a surface layer to form a carbon dioxide gas stream.

The surface layer only needs to be at least partially composed of a carbon dioxide permeable member that is permeable to carbon dioxide gas.Therefore, the surface layer covering the bag containing the indicator and the printing layer is: It is not necessary to form all of this with a carbon dioxide permeable member, and it is also possible to form a part with this member and the other with a carbon dioxide barrier member. The carbon dioxide permeable member constituting at least a part of the surface layer is selected from those capable of adjusting the time during which the color tone of the carbon dioxide gas changes over time according to the time until the contents are altered. Preferably, the member is selected from those having a carbon dioxide gas permeability in the range of 50 (mLVm ² '24 hours) or more and 20000 (mL / m ² · 24 hours) or less. Preferred materials that can satisfy the carbon dioxide gas transmission rate include, for example, polyamide; polyester (ΡΕΠ; cyclic polyolefin (COC); polyvinyl chloride; polyethylene (for example, low-density polyethylene, etc.); and polypropylene (unstretched). Polyolef And the like. Among the above, for example, low-density polyethylene, unstretched polypropylene, and the like have heat sealing properties and can be preferably used in the present invention. The carbon dioxide gas permeability can be appropriately adjusted by changing the thickness of a film made of these materials.

In the present specification, the above-mentioned carbon dioxide gas permeability is measured by the same pressure method using PERTMATRAN manufactured by MOCON.

When a part of the surface layer covering the print layer is formed of a carbon dioxide gas permeable member and the remainder is formed of a carbon dioxide gas barrier member, the carbon dioxide gas barrier member used has a carbon dioxide gas permeability of 50 ( mm ² -24 hr) or less. Examples of the film include a transparent vapor-deposited film in which silica or alumina is vapor-deposited on a base film made of a synthetic resin such as a polyester (PET) film or a polyamide film; a polyvinylidene chloride (PVDC) film;

(PVA) film; Ethylene vinyl acetate copolymer (EVOH) film and the like. These films can be singly or laminated and ffl. These films can be further laminated with another resin film in order to obtain heat resistance and the like according to the purpose. Examples of other resin films include, for example, polyamide films capable of obtaining piercing strength.

As an example of an embodiment in which a part of the surface layer covering the print layer is formed of a carbon dioxide gas permeable member and the remainder is formed of a carbon dioxide gas barrier member, an embodiment as shown in FIG. 5 described below is exemplified. Can be. That is, in this embodiment, a printed layer is formed as an indicator on one of the front and back surfaces of the carbon dioxide gas-based support, and the surface of the carbon dioxide-permeable member is formed on the support including the print layer. By forming the layer, one surface of the printing layer is covered with a carbon dioxide permeable member, and the other surface is a carbon dioxide barrier support layer. Such coating can be performed, for example, by a dry lamination method using a suitable adhesive according to a conventional method.

By appropriately selecting the material of the carbon dioxide permeable member forming the surface layer and the thickness of the surface layer of the member portion, the carbon dioxide permeability of the surface layer can be appropriately adjusted, and thus the carbon dioxide indicator The time required for the amount of carbon dioxide required to change the color tone of the pH indicator to pass through the surface layer can be appropriately changed. In the present invention, this surface layer By adjusting the carbon dioxide permeability of the package, the time when the contents deteriorate after opening the package and the time when the color tone of the carbon dioxide indicator changes, more precisely, the color tone of the pH indicator in the carbon dioxide indicator Match the time of change. For example, when low molecular weight polyethylene is used as the material of the carbon dioxide permeable member used as the surface layer, the thickness is set to about 20 to about 200 m, and when the thickness is about 20 m, the carbon dioxide gas is used. the transmittance 50 (mL7m ² '24 hours) or more, 500 (mLVm ² -24 hours) less than the can and child, also, in the case of a thickness of about 200 At m, a carbon dioxide gas permeability 500 (mL7m ² '24 hours) or more, but less than 20000 (mL7m ² -24 hours). The carbon dioxide gas permeability does not depend only on the material and thickness of the carbon dioxide gas permeable member, but also slightly changes depending on, for example, temperature and humidity.

When packaging a chemical solution containing a bicarbonate-containing chemical solution in a plastic drug solution container having carbon dioxide gas permeability and packing it with carbon dioxide gas replacement, it is necessary to wait until the chemical solution inside the container becomes clean after opening the package. The time (period during which the chemical solution can be used safely) depends on the carbon dioxide permeability of the chemical solution container, but has a predetermined value. This period can be determined in advance by measuring the pH of the drug solution in the container over time. According to the present invention, the carbon dioxide permeability of the surface layer constituting the carbon dioxide gas indicator is adjusted to a desired value according to the safe use period of the container containing the chemical solution, so that the time when the chemical solution changes and the pH indicator are changed. By matching the time when the color tone changes, the above period was successfully displayed as the color tone change.

In the present invention, when a pH indicator in the form of a solid or printed layer is used, in order for the pH indicator to change color, these forms need to be able to maintain a water-containing state. That is, they need to contain a suitable solvent or water retention agent (humectant) or water absorption agent. The pH indicator in a liquid form is prepared by dissolving or dispersing the pH indicator in the solvent using a similar suitable solvent.

Here, examples of the solvent include aromatic acid, hydrogen hydrogen, esteri, alcohols and water. Of these, water or alcohols are particularly preferred. Examples of the water retention agent (humectant) include, for example, glycerin, propylene glycol, polyethylene glycol and the like. Of these, glycerin holds the solvent such as water in the printing layer obtained by its blending, and absorbs carbon dioxide gas. And facilitates the color reaction of the pH indicator.

As the water absorbing agent, a substance which does not show extreme acidity or basicity when containing a solvent such as water and has a high white color can be desirably used. As such a substance, for example, starch, kaolin, synthetic silica, glass, microcrystalline cellulose, ion-exchange cellulose, aluminum gayate and the like can be used.

A preferred ink composition for detecting carbon dioxide gas further contains a binder, and further contains an alkaline substance.

The binder has a function of fixing a pH indicator, an optional alkaline substance, a water-absorbing agent, and the like to the support. Examples of the binder include polyacrylic acid, polyvinyl alcohol, polyvinyl butyral, polypinyl acetate, polyvinyl acetate, polyurethane, partially saponified vinyl acetate, and the like. As the binder, those having the property of dissolving or dispersing in a solvent can be preferably selected. Examples thereof include polyvinyl alcohol when water or alcohols are used as the solvent.

The alkaline substance used as needed in the ink composition for detecting carbon dioxide gas is preferably any one of a hydroxide, a carbonate, and a hydrogen carbonate. Specific examples include sodium hydroxide and sodium hydrogen carbonate.

As a pH indicator, the display color is accompanied by a change in color tone due to the influence of carbon dioxide gas.In other words, when carbon dioxide gas is dissolved in an appropriate liquid containing the pH indicator, carbon dioxide gas is released from the solution into the atmosphere As a result, the pH of the liquid changes, and a liquid whose color tone changes according to the pH change can be used. Table 1 below shows examples of preferred pH indicators and their color change (the relationship between color tone and pH). When a pH indicator that changes color in a higher pH range among the pH indicators exemplified in Table 1 is used, it is preferable that the liquid containing the indicator further contains an alkaline substance. table 1

pH indicator Color change dan (Relation between color and pH)

New Reed Red 6.8-8.0 Yellow

Phenolate yellow 6.8-8.4

ヮ Reno ¹ yellow color 7.2-8.8 colors

ex-no-no-one-soleno: y-re-no pink 7.3-8.7 green

Kusore Roh yellow 7.4-8.6 redness force s Katsuta揭¹ B

Sugucleno Nore /, ^ Norele Yellow 7.4-9.0 Bluish purple

Etylbis (2,4-dinitroph

Colorless 7.5-9.1 blue

Enil) acetate

Timor bull I yellow 8.0-9.6 blue

Ρ-Xylenol blue colorless 8.0-9.6 blue

Phenolphthalein Colorless 8.3-10.0 Red In the table, the description of the color change means that the color falls below the central pH range, indicating the color on the left, and the color change above the center indicates the color on the right.

One of the above pH indicators can be used alone, or two or more can be used in combination. When a pH indicator of 2 or more is used, even when the concentration of carbon dioxide changes at a low concentration (for example, 0.1-10.0%), this change is regarded as a clear color change, and the deterioration of the chemical solution can be perceived. There is.

One of the preferred pH indicators is meta-cresol purple because of its easiness and easy change in color reaction.

The pH indicator shown in Table 1 above can be determined not only by the change in the color tone of the indicator itself, but also by the change in the color tone due to color mixing with other color pigments. For such a purpose, a coloring agent can be added to the ink composition for detecting carbon dioxide gas.

By adding a colorant and mixing it with the color of the carbon dioxide detection ink composition, for example, when the change in the color tone of the indicator itself is difficult to judge visually, or it is not the desired color tone in design. Sometimes, colors that are easy to judge visually, or It can be changed to a desired color tone on design.

Further, for the same purpose, a white 支 ^ ¾ separated part can be applied, and a ^ part using a carbon dioxide detection ink-pirate can be provided thereon.

Coloring agents include, for example, Food Red No. 2 (Amaranth), Food Red No. 3 (Eris Mouth Shin), Food Red No. 40 (Arraletto AC), Food Red No. 102 (New Coccin), Food Red No. 104 (Phloxine) Edible red No. 106 (acid red), red coloring agents such as natural cochineal pigments; edible yellow No. 4 (Yuichi Tolazine), edible yellow No. 5 (Sunset Yellow I FCF), natural safflower yellow pigment, etc. Yellow coloring agents: Blue hardeners such as Food Blue No. 1 (Purianto Blue I FCF) and Food Blue ^ 2 (Indigo Carmine). A similar change in color tone can be obtained by using a colored support as a support in addition to adding a colorant to the ink composition.

Further, in addition to the above-mentioned components, various chemicals for improving ink coatability, such as surfactants, varnishes, compounds, and drying inhibitors, may be added to the ink composition for detecting carbon dioxide gas. Is also possible. However, it is desirable that these compositions be in a range that does not adversely affect the color tone change of the pH indicator in the ink composition.

Printing methods, such as screen printing, intaglio printing, gravure printing, etc., and coating methods, such as mouth-coating, spray coating, dip coating, etc., are examples of methods for applying the ink composition. Will be ^ ffl.

The indicator used in the present invention desirably has a relatively large and constant amount of the ink composition applied. Therefore, it is preferable to use a printing method as the ink composition applying method. In general, the preferred ranges of the coating amount and the film thickness are about 0.1 to ²⁰ g / m2 and the film thickness of about 0.1 to 10 m when using any printing method. Monkey

By printing the indicator on the package and covering the indicator with a surface layer, a package having a carbon dioxide gas indicator can be produced.

In addition, for example, a packaging provided with a carbon dioxide gas indicator portion is obtained by bonding a carbon dioxide gas indicator obtained by continuously printing the indicator portion on a suitable support and coating the indicator portion with a surface layer to the package. You can also get your body. In this case, since the support can be wound and supplied, formation of the indicator on the support is performed by gravure. Printing or flexographic printing is appropriate.

As the supporter, a neo-material that is gas-permeable, does not react with the ink fiber, and does not adversely affect the color change of the ρΗί¾¾ drug can be selected. As such a body, for example, a rope, a sword, a non-invasion, a slimming film, or the like can be used depending on the purpose and use form. The support may be formed from the above various materials separately from the surface layer. Further, the material of the support may be appropriately selected, and the support may be used as a part or all of the surface layer.

In addition, the indicator may be a printed layer having a pattern of characters, pictures, etc. _{(In view} of the decorative aesthetics and design of the package, formation of such a pattern is preferable. If you select a character as, you can also use it as a label that prints the product name, etc. Furthermore, you may use ¾ ^ to make the indication part easier to see.

In the method of the present invention, it is important to dispose the carbon dioxide gas together with the contents in the carbon dioxide gas-filled package. With the use of this carbon dioxide gas overnight, the package is opened, the carbon dioxide gas escapes from the package, the inside of the package communicates with the atmosphere, and then the! S, which changes during the course of the aging with time, especially the contents The period during which the drug can be used safely can be visually judged by the change in the display color of the medicine during the carbon dioxide gas jetting. (2) Contents

In the method of the present invention, the contents packaged with carbon dioxide together with the carbon dioxide indicator in the package can be stably stored in a carbon dioxide gas atmosphere. Contents that deteriorate (degrade), for example, foods and drinks, pharmaceuticals, etc., and are contained in, for example, a plastic container having carbon dioxide gas permeability.

Here, the plastic container having carbon dioxide permeability is a plastic having the same carbon dioxide permeability as the carbon dioxide permeable member constituting the surface layer of the carbon dioxide indicator described above, for example, polyamide, polyester, coc The container may be made of polyvinyl chloride, polyethylene, polypropylene, or the like. In particular, when selecting a bicarbonate-containing chemical solution as the content, the container (chemical solution container) is preferably a plastic container (bottle, bag, etc.) formed of polyethylene, polypropylene, polyvinyl alcohol, or the like. .

The chemical solution container need not be a single-chamber container, but is a multi-chamber container having two or more storage chambers each capable of independently storing a chemical solution, and having a partition wall capable of communicating between adjacent chambers. There may be. That is, the multi-chamber container has, for example, a temporary sealing portion, which can release the space between the chambers by a predetermined impact, whereby the liquids contained in the respective chambers are mixed, Can be prepared.

For example, a bicarbonate-containing chemical solution as a content contained in the container has a property of releasing carbon dioxide gas and losing its medicinal properties. Therefore, the liquid is converted into a bicarbonate component and carbon dioxide gas by carbon dioxide replacement packaging. It is packaged and stored while keeping the balance of carbon dioxide and preventing the release of carbon dioxide gas.

The bicarbonate-containing chemical solution contains sodium hydrogencarbonate as an active ingredient as a bicarbonate as an essential component, and a component that provides sodium ions such as sodium chloride, depending on its use (pharmaceutical use). And a component providing citrate ions such as citrate, sodium citrate, and the like. In addition, a component capable of providing at least one of magnesium ion and calcium ion such as magnesium chloride and calcium chloride can be included. However, since these components may react with sodium bicarbonate to form a precipitate, when preparing a bicarbonate-containing chemical solution by combining these components, the above-mentioned quencher is used to prevent precipitation. A component providing an acid ion is blended. Therefore, when a bicarbonate-containing drug solution is contained in a single-chamber container, the drug solution contains components providing sodium hydrogencarbonate, magnesium ions and κ or calcium ions, and components providing citrate ions. Force s preferred.

In the case of a multi-chamber container, the first chamber of the multi-chamber container contains a solution containing sodium hydrogencarbonate, and the second chamber contains a solution containing a component that gives magnesium ions and / or calcium ions. There is no risk of precipitation. Of course, even in the case of this multi-chamber container, the first chamber may contain a solution containing a component providing sodium hydrogencarbonate, magnesium ion and calcium or calcium ions, and a component providing quench ion. it can. In this case, in the second chamber, the diluting solution and other chemical components of the first chamber container, for example, in the case of a bicarbonate-containing chemical solution intended for use as an intraocular perfusion solution, etc. It can contain a solution containing at least one of thione and dextrose.

Further, the bicarbonate-containing chemical solution may contain, if necessary, sodium chloride, potassium chloride, hydrochloric acid, sodium hydroxide, and sterilized purified water. In the case of a multi-chamber container, these components can be contained in one or both of the first and second chambers containing sodium bicarbonate.

As a typical example of a bicarbonate-containing drug solution, for example, sodium bicarbonate injection solution included in the Japanese Pharmacopoeia as a bicarbonate-containing drug solution for correction of acidosis, etc. can be mentioned. . Specific examples thereof include an injection solution containing 70 g (7%) of sodium hydrogen carbonate in lOOOOmL of water for injection ("Meiron" (registered trademark) manufactured by Otsuka Pharmaceutical Factory Co., Ltd.). (3) Carbon dioxide replacement packaging

In the method of the present invention, the above-mentioned contents are packaged together with a carbon dioxide gas by replacing the carbon dioxide gas. The packaging is, for example, a bicarbonate-containing chemical solution contained in a plastic drug solution container having carbon dioxide gas permeability, which is one of the preferable contents. Is placed in a suitable carbon dioxide gas barrier package, and the inside of the package is replaced with carbon dioxide gas and sealed.

When a bicarbonate-containing chemical solution containing, for example, 0.1 to 5% by weight of bicarbonate is contained as the bicarbonate-containing chemical solution, the carbon dioxide gas concentration in the package is preferably 0.5 to 10% by volume, and more preferably 1 to 9% by volume, more preferably 1 to 7% by volume. Further, when containing a bicarbonate-containing chemical solution containing 5 to 20% by weight of bicarbonate, the concentration of carbon dioxide in the package is preferably 10 to 90% by volume, more preferably 20 to 80% by volume, and Preferably, the content is 30 to 70% by volume.

Carbon dioxide gas is weakly acidic when dissolved in water. In the carbon dioxide gas ingestion used for the package of the present invention, if the carbon dioxide gas is sufficiently present in the indicator, the pH value becomes low. However, the pH value increases as the level of carbon dioxide gas decreases, and when the pH value reaches a certain value, the color of the pH indicator changes. When a structure containing an alkaline substance in the indicator, it is possible to increase the _P H of the indicator as compared to the case without the該A alkaline substance. Therefore, a pH indicator that can change color in a higher pH range can be used for the obtained indicator.

The carbon dioxide replacement package used in the present invention may be, for example, a mixed gas of carbon dioxide and air having an arbitrary mixing ratio, a mixed gas of carbon dioxide and nitrogen gas, or a mixed gas of carbon dioxide, nitrogen gas and air. A gas containing gas is sealed in the package before the package is sealed, or a carbon dioxide-generating type oxygen scavenger such as “Ageless G” (registered trademark) manufactured by Mitsubishi Gas Chemical Company is used. It can be implemented by placing it and sealing it. In the latter case, the carbon dioxide concentration in the package can be controlled by adjusting the concentration of a carbon dioxide gas source such as oxygen in the package.

According to the present invention, when the package is opened and the carbon dioxide gas inside the package is released into the atmosphere by using the carbon dioxide gas indicator, the contents change over time in response to the change in the carbon dioxide gas concentration. The time required for alteration (due to the generation and release of carbon dioxide) of this content is determined by the change in the display color of the carbon dioxide gas, so that the content can be used safely (can exhibit the desired medicinal effect). ) You can easily check the period. In the method of the present invention, the arrangement of the carbon dioxide gas in the package may be, for example, a method of simply adhering a carbon dioxide indicator to the surface of the chemical solution container containing the contents or a material constituting the package. The method includes forming a print layer on the inner surface and coating it with a surface layer.

(4) Package obtained by the method of the present invention

Hereinafter, the package obtained by the method of the present invention will be described more specifically with reference to the drawings.

FIG. 1 is a schematic sectional view showing one embodiment of the carbon dioxide gas used in the present invention.

As shown in the figure, the carbon dioxide indicator includes a bag 63 and a tablet 62 sealed in the bag 63. The bag 63 has a thickness of, for example, 20 to 200 m. It can be composed of a polyethylene film with a carbon dioxide permeability of more than 500 (mL7m2'24 hours) and less than 20000 (ml_ / m2'24 hours). In addition, as an example of the tablet 62, a material in which a _pH indicator such as meta-cresol purple or a humectant is impregnated into a filler containing crystalline cellulose as a main component is molded according to a conventional method. Tablets.

FIG. 2 is a schematic sectional view showing another embodiment of the carbon dioxide gas used in the present invention.

As shown in the figure, the carbon dioxide indicator comprises a bag 64 and a liquid material 65 sealed in the bag. ^ f * «4 can be composed of the same film as ^ # 63 shown in FIG. Further, as the liquid material 65, for example, a solution obtained by mixing a pH agent such as metacresol solvent in a solvent containing propylene glycol, for example, can be preferably used.

FIG. 3 is a front view showing another example of the carbon dioxide gas used in the present invention, and FIG. 4 is a sectional view thereof.

As shown in the figure, the indicator 10 is provided on both surfaces of a support 1 made of, for example, a polyethylene terephthalate film, for example, with cresol purple, sodium carbonate, polyvinyl acetate resin, microcrystalline cellulose, and the like. An i ^ part 2 obtained by applying a carbon dioxide gas detection ink composition made of water by screen printing with a hollow circular (donut-shaped) pattern is provided, and the entire separation 1 for fl 該 P2 is provided. It has a configuration surrounded (covered) by a surface layer 3 made of a carbon dioxide permeable member. The indicator part 2 of this indicator has a purple color in the air. In FIGS. 3 and 4, the indicator 2 is provided on both surfaces of the support 1, but a configuration in which the indicator is provided on only one side may be applied.

FIG. 5 is a sectional view showing another example of the carbon dioxide gas used in the present invention.

As shown in the figure, this example is an example in which the indicator 2 is provided only on one side of the support 71. The support 71 has a carbon dioxide gas barrier property made of, for example, a film obtained by depositing a silicon resin on a polyester resin. Can be used. The indicator 2 is provided, for example, on a layer having a carbonic acid gasparous property (support 71), It can be formed by applying an ink composition for detecting carbon dioxide gas composed of tocresol fluorin, sodium carbonate, polyvinyl acetal resin, microcrystalline cellulose and water in a circular pattern by screen printing. A surface layer 73 made of, for example, a polyethylene film is formed on the indicator 2 so as to seal the indicator. In the carbon dioxide gas indicator 70 (indicator 2 + surface layer 73), the carbon dioxide gas in the indicator 2 is transmitted and released only from the surface layer 73 (layer 73 having carbon dioxide permeability). Since ¾t 1 has a carbon dioxide gas parity, no carbon dioxide gas is emitted from this side. Therefore, if a package composed of the carbon dioxide indicator 70 and the ## 71 shown in this example is made with the support on the outside and the surface layer 73 on the inside, for example, the package will be , Charcoal 包装 A package with a swing indicator 70.

FIG. 6 is a schematic view illustrating a first example of a package obtained by carbon dioxide replacement packaging obtained by the method of the present invention.

As shown in the figure, this gas replacement package 20 comprises a carbon gas permeable chemical solution container 11 containing a chemical solution, and a carbon dioxide gas indicator 10 similar to that shown in FIGS. ：: At 12 the carbon dioxide dragon was packaged using the replacement gas 13. The chemical solution container 11 is preferably made of low-density polyethylene of, for example, 0.910 to 0.925 gZcm3. As the replacement gas 13, for example, a mixed gas of 90 to 99.5% by volume of nitrogen and 0.5 to 10% by volume of dioxide can be used. Further, the exterior body 12 is preferably made of a laminated filem.

The display color of the indicator in this package is yellow when the package 20 is manufactured (when the carbon dioxide gas is replaced and packaged). When the package is opened, the carbon dioxide gas enclosed in the package is scattered into the atmosphere, and the gas atmosphere inside the indicator 10 changes accordingly. Outflow). As a result, the color tone of the display color of the carbon dioxide indicator changes from yellow to brown and further to purple. In the method of the present invention, the time required for the change of the color tone is adjusted to the time required for refining the contents by, for example, adjusting the thickness of the surface layer of the indicator 10. This makes it possible to easily confirm whether the contents are in a usable state or have been altered by visually recognizing the change in the color tone of the carbon dioxide gas indicator. FIG. 7 is a schematic view showing a second example of the package body obtained by the carbon dioxide replacement packaging obtained by the method of the present invention.

As shown in the figure, the package 30 has a carbon dioxide gas container 18 composed of a finger 2 and a surface layer 5 arranged on a part of the surface of a carbon dioxide permeable chemical solution container 14 containing a chemical solution. In addition to the carbon dioxide gas barrier property, a fiber gas 13 is used to replace and package with carbon dioxide gas.

Also in this figure, the chemical solution container 14 is preferably made of low-density polyethylene having a density of, for example, 0.910 to 0.925 gZcm3. More specifically, the carbon dioxide gas indicator 18 is composed of an indicator 2 formed by, for example, screen printing on a part of the outside of the chemical solution container 14 as a support, and a carbon dioxide gas transmission coating the indicator 2. And a surface layer 5 made of a conductive material. The replacement gas 13 in the sequestration is, for example, a mixed gas of 90 to 99.5% by volume and carbon dioxide 0.5 to 10% by volume.

Also in this package # 30, as in the package shown in Fig. 6, by visually checking the change in the color tone of the display color of the carbon dioxide gas indicator, it is determined whether the contents are kept usable or not. Can be easily checked.

Note that the second example (FIG. 5) of the coal indicator can be applied instead of the coal indicator 18. In other words, the carbon dioxide gas indicator shown in FIG. 5 is created and attached to the chemical solution container 14, so that the carbon dioxide indicator 18 can be used instead.

FIG. 8 is a schematic diagram showing a third example of a package obtained by carbon dioxide replacement packaging obtained by the method of the present invention.

As shown in FIG. 8, the package obtained by the present invention may be one in which the carbon dioxide gas indicator 70 is integrated with the outer package 12 by a method such as bonding.

In the package 40, the carbon dioxide indicator 70 is provided with a finger 2 by screen printing or the like on its inner surface, as shown in FIG. 5, using the exterior 12 made of a laminated film of carbon dioxide gas barrier as a support, for example. It can be formed by coating the it ^ 2 with a carbon dioxide gaseous surface layer 73. More preferably, the production of the packaging # 40 is performed by, for example, a carbon dioxide gas coating in which two laminated films of FIG. 5 US Pat. A film with a surface Layer 72 is folded inward with the 73 side inward, and the two sides are heat-sealed so as to form a bag. After placing the contents 16 in the obtained bag, the inside of the bag is filled with, for example, nitrogen 90 It can be carried out by hermetically sealing the opening of the bag-like material with a heat seal while replacing it with a gas mixture 13 of 999.5% by volume and of carbon dioxide 0.5 to 10% by volume.

The package obtained by the method of the present invention is capable of indicating and confirming, by opening the exterior material, the time during which the contents are deteriorated, that is, the period during which the contents can be used safely and effectively, by changing the color tone of the carbon dioxide gas indicator. is there. In addition, since the package itself completely covers the indicator with a surface layer, it has good adhesion, light resistance and heat resistance. In other words, the printed layer is easily affected by an external impact and is easily peeled off. However, in the present invention, since the indicator is covered with the surface layer, there is no need to worry about peeling. Further, the composition of the indicator may include components that are degraded by light or heat, but the indicator is covered with a surface layer. However, their deterioration due to heat irradiation can be reduced.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a front view showing one embodiment of a carbon dioxide gas indicator used in the present invention.

FIG. 2 is a sectional view showing another embodiment of the carbon dioxide indicator used in the present invention.

FIG. 3 is a cross-sectional view illustrating another embodiment of the carbon dioxide gas used in the present invention.

FIG. 4 is a cross-sectional view of the carbon dioxide indicator shown in FIG.

FIG. 5 is a cross-sectional view illustrating another embodiment of the carbon dioxide indicator used in the present invention.

FIG. 6 is a schematic diagram illustrating a first example of a gas replacement package obtained by the method of the present invention.

FIG. ⁷ is a schematic view showing a second example of the gas replacement package obtained by the method of the present invention.

FIG. 8 is a schematic diagram showing a third example of the gas replacement package obtained by the method of the present invention. FIG. 9 is a top view showing a chemical solution container used in the method of the present invention.

In each figure, 1 is a support, 2, 62 and 65 are indicators, 3 and 5 are surface layers, 10 is a carbon dioxide gas indicator, 11, 14 and 16 are containers for chemicals, 12 is an exterior body, and 13 is Indicates carbon dioxide-containing gas.

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, Production Examples and Test Examples of carbon dioxide gas used in the present invention are shown as Reference Examples 1 to 8.

Reference example 1

An ink composition was obtained by finely dispersing a carbon dioxide sensing ink composition 1 having the following composition with a paint conditioner.

Meta-cresol purple 0.1g

Sodium carbonate 1.5g

17.5g of polyvinyl alcohol

Microcrystalline cellulose 119

70g water

As a support, weighed 140 g / m ² JIS standard P 3801 filter paper for chemical analysis was applied, and 2.5 g iri of the ink composition 1 for carbon dioxide detection prepared above by the screen printing method was applied thereto. For 1 hour to obtain a printed layer having ^a water content of 0.5 g / ma and serving as an indicator of the carbon dioxide gas indicator.

Next, a vinylidene chloride-coated polyamide film (thickness: 25 m, Kojin Co., Ltd .: Ponyl) Z low-density polyethylene film: 0 ¥ 50 m, density: 0.930 g / cm3 (Dagegaku Co., Ltd .: Ultzex) Using a carbon dioxide gas barrier film (acid gas ratio: 0.3ml / rri · 24hrs), a bag with a content of 50mL was prepared. In the obtained bag, the above-mentioned having the printed layer was put, and the inside of the bag was sealed with air or a mixed gas of a gas of predetermined concentration, carbon dioxide and air, and then sealed to obtain a package. .

Fig. 2 shows the results obtained by changing the color tone of the printed layer in parcel S #: although the CO2 boat in the mixed gas used was variously changed.

Reference example 2 In Reference Example 1, the carbon dioxide gas detecting ink composition 1 was changed to the carbon dioxide gas detecting ink composition 2 having the following composition, and the support was changed to a 12 m-thick polyester film (emblem manufactured by Unitichi Riki Co., Ltd .: emblem). A package was prepared in the same manner except for the change, and the color tone of the printed layer in the package was keyed. The obtained results are shown in FIG.

Metacresol Purple 0.1g

Sodium hydroxide 1.0g

17.5 g of polyvinyl acetate resin

11g microcrystalline cellulose

70g water

Reference example 3

In Example 1, a package was prepared in the same manner except that the carbon dioxide gas detection ink composition 1 was changed to the carbon dioxide gas detection ink composition 3 having the following composition, and the color tone of the printed layer inside the body was determined. The results obtained are shown in FIG.

<3 formulas for carbon dioxide sensing ink composition>

Metacresol purple 0.1 g

1.5 g sodium carbonate

Polyvinyl acetal resin 17.5g

78.8g of water

Example 4

A package was prepared in the same manner as in Reference Example 1 except that the carbon dioxide gas detection ink composition 1 was changed to the carbon dioxide gas detection ink composition 4 having the following composition, and the color tone of the print layer in the package was observed. did. Table 2 shows the obtained results.

<4 formulas for ink composition for carbon dioxide paste>

0.1 g of metacresol purple

1.5 g sodium carbonate

Polyvinyl acetal resin 19.7g

78.8g of water

Glycerin 11α Reference Example 5

A package was prepared in the same manner as in Reference Example 4 except that the carbon dioxide gas detection ink composition 4 was changed to the carbon dioxide gas detection ink composition 5 having the following composition, and the color tone of the printed layer in the package was observed. did. Table 2 shows the obtained results.

Ink for carbon dioxide gas me / 5 prescription>

Metacresol Purple 0.1g

1.5 g sodium carbonate

Polyvinyl acetal resin 19.7g

11g microcrystalline cellulose

2- (2-π-butoxyethoxy) ethyl acetate 78.8 g

Glycerin 11g

Table 2

However, 0% in the carbon dioxide gas concentration (%) in Table 2 includes about 0.04%, which is the same concentration as the carbon dioxide contained in the atmosphere, because this test uses air. However, the concentration of carbon dioxide in the atmosphere (0.04%) shall be displayed as 0% for convenience.

As shown in Table 2, the printing layer formed by the carbon dioxide gas detecting ink composition used in the present invention has a specific color tone according to the carbon dioxide gas concentration in the contained atmosphere. In particular, the color tone is different when the carbon dioxide concentration is 0% than when it is 1-10%. Therefore, it is clear that the concentration of carbon dioxide in the atmosphere can be easily detected by visually observing the color tone change. Reference example 6

A package was prepared in the same manner as in Reference Example 1, except that the carbon dioxide detection ink composition 1 was changed to the carbon dioxide detection ink composition 6 having the following composition.

<6 formulas for ink composition for carbon dioxide detection>

Cresol Red 0.1g

1.5 g sodium carbonate

Polyvinyl acetal resin 19.7g

78.8g of water

The color tone of the printed layer in the obtained package was reddish brown in an atmosphere with carbon dioxide and reddish purple in an atmosphere without carbon dioxide.

Reference Example 7

A package was prepared in the same manner as in Reference Example 1, except that the carbon dioxide detection ink composition 1 was changed to a carbon dioxide detection ink composition 7 having the following composition.

<7 formulas for ink composition for carbon dioxide detection>

Bromothymol blue 0.1g

Urethane resin 26.1g

61.3g of water

The color tone of the printed layer in the obtained package was blue in an atmosphere with carbon dioxide and purple in an atmosphere without carbon dioxide.

Reference Example 8

A package was produced in the same manner as in Reference Example 1, except that the carbon dioxide gas sensing composition 1 was changed to the carbon dioxide gas sensing composition 8 having the following composition.

<8 formulas for ink composition for carbon dioxide detection>

α-Nuff! ^ One-phthalphthalein 0.1g

Urethane resin 26.2g

Microcrystalline cellulose11g

Water 61, 3g

The color tone of the printed layer in the obtained package was light blue in an atmosphere with carbon dioxide gas and blue in an atmosphere without carbon dioxide gas. Hereinafter, examples will be given to describe the present invention in further detail.

Example 1

A polyethylene terephthalate layer having a thickness of 12 m (Unitechika: "Emblem"), and an adhesive layer provided on this layer (Toyo Morton Co., Ltd. "AD-393 / TCSJ, thickness: 5 / zm) and a 20 mm x 20 mm tack seal with a peelable support sheet (Nisco Tack Label made by Iwata Rebel, 50 m) were prepared and the following formulation was applied to the center of the polyethylene terephthalate layer surface. The ink composition was printed by a gravure printing method so as to have a thickness of 1 m in a circular shape of 10 mm × 1 Omm to form an indicator having a water content of 0.5 g / m ² .

Next, a linear low-density polyethylene film (LLDPE, thickness 60 nm, carbon dioxide gas permeability 6900 mL m2-24 hours) is laminated on the layer on which the indicator is formed by dry laminating as a surface layer, and tack sealing is performed. I got a type of carbon dioxide gas overnight.

The cross-sectional configuration is as follows: support sheet / adhesive layer Z polyethylene terephthalate (PET) (I2wm) / printing layer LLDPE (60 xm).

Meta-cresol purple 0.9g

7 g Sodium oxide 3.1 g

Glycerin 4.5g

Water 100.0g

The obtained tackle-type carbon dioxide gas indicator is used to hang a ^ S container having a communicable partition wall as shown in Fig. 9, i.e., a double bag made of carbon gas polyethylene having a size of about 20cm x 30cm. Attached to the film and folded in two, polyamide film 0P 15m) Z polyvinyl alcohol (thickness 18m) Z polyethylene 0? 60 im) about 26x28cm size 1 ^ #: (carbonated Gas: 0.3ml / rri, 24hre), and gas replacement packaging with a mixture of 10% by volume of carbon dioxide and 90% by volume of empty gas to obtain a package having the structure shown in Fig. 7. Was.

The double bag 90 shown in FIG. 9 is a bag composed of a pair of polyethylene films whose peripheral edges are sealed. , And has a communicable partition wall 91 that divides the inside of the bag into a first chamber 92 and a second chamber 93. The first and second chambers 92 and 93 contain the following liquid chemicals, respectively. Have been. On the side of the first chamber 92 of the double bag 90, a hanging member 94 that can be hung on a hook or the like is provided. The carbon dioxide gas can be preferably stuck on the vicinity of the hanging member 94. Further, on the side g of the second chamber 93, there is provided an outlet 95 communicating with the second chamber 93 and a cap 96 capable of opening and closing the outlet.

Oxyglutathione 0.09g

Dexterous mouth 0.46g

3.32g sodium chloride

Chloride power 0.19g Sodium hydroxide

Amount to make the whole sterilized purified water 150mL

pH 4.5

Hydrogen carbonate sodium 1.05g

Sodium acetate trihydrate 0.30g

Sodium sodium citrate dihydrate 0.50g

Calcium chloride dihydrate 0.08g

Magnesium chloride hexahydrate 0.1 Og Sodium hydroxide

A volume of 350 mL of sterile purified water

pH 7.8

The pH of the chemicals contained in the first and second chambers immediately after mixing is 7.45, and when the pH is in the range of 7.1 to 8.1, it can be used sufficiently and effectively. If the pH exceeds 8.1, there is a problem that the intended effect of the drug solution cannot be exhibited during use.

Create a total of 7 same packages as above, open them at the same time, break the partition and mix the two liquids, immediately after opening, 30 minutes, 1 hour, 2 hours, 3 hours, After 5 hours, 6 hours, and 12 hours, it was present in the space inside the drug solution container and kept in equilibrium with this solution. For gas containing C0 ₂ and measuring the C0 ₂ concentration, the pH was measured of the chemical solution at the same time. At the same time, the color tone of the carbon dioxide indicator was adjusted.

Table 3 shows the obtained results.

Table 3

“0.0”% in the carbon dioxide concentration at the elapsed time of 12 hours in Table 3 indicates that the carbon dioxide concentration in the chemical solution container was the same as that in the atmosphere (about 0.04%). In the following tables, "0.0J means the same thing.

As is evident from Table 3, the concentration of carbon dioxide in the drug solution container gradually decreased over time, reaching about 0.1% 6 hours after opening the package. The pH of the drug solution at that time was 8.1. In contrast, the color tone of the carbon dioxide gas indicator was yellow immediately after opening, turned brown 2 hours later, and turned blue 6 hours later. From this, it is clear that the color tone of the carbon dioxide gas used in the present invention can change the color tone well reflecting the change of the carbon dioxide gas concentration and the pH of the chemical solution. That is, when the indicia is yellow to brown, the pH of the chemical is 7.7 to 8.0, and it can be determined that the chemical is sufficiently usable. When the indicator is blue, the pH of the drug solution is 8.1 or less, and it can be determined that the drug solution cannot be immediately turned over or is in a fine state.

Comparative Example 1

Instead of LLDPE (thickness 60 μm, carbon dioxide permeability 6900 mlJm2-24 hours) used as the surface layer in Example 1, LLDPE (thickness 25 μιη, carbon dioxide permeability 15000 mL7 m2)

• 24 hours) In the same manner, a tackle-type carbon dioxide gas indicator was obtained.

Using the obtained tackle-type carbon dioxide gas indicator, a package was prepared in the same manner as in Example 1, and immediately after opening and after a lapse of a predetermined time, an empty space in the chemical solution container was similarly formed. The concentration of carbon dioxide in the gas between them and the pH of the drug solution were measured, and the color tone of the carbon dioxide indicator changed. Note that the measurement time is slightly different from that of Example 1. Table 4 shows the obtained results.

Table 4

As shown in Table 4, in Comparative Example 1, the color tone of the carbon dioxide gas indicator turned blue in 2 hours. However, in the past 2 hours, the pH of the chemical solution is 7.9, and 1.0% of carbon dioxide still remains in the chemical solution container, and the chemical solution can still be used sufficiently. That is, according to Comparative Example 1, even when the chemical solution can be used, the color tone of the carbon dioxide gas has already changed to blue, and the chemical solution cannot be actually used. The color tone does not change. Therefore, in this example, it is clear that it is not possible to judge the deterioration of the chemical solution by the change in the color tone of the carbon dioxide gas indicator.

Example 2

LLDPE (thickness 30 Λπι), COC (cyclic olefin copolymer, thickness 30 wm (manufactured by Mitsui Chemicals, Inc., Abel)) as in Example 1 and LDPE (thickness 30) as in Example 1. m) laminated film (carbon dioxide permeability: 490 mL / m2 for 24 hours), and heat sealed the three sides to form a bag. The ink of Example 1 was placed in the bag. After enclosing a liquid having the same composition as the composition, the remaining one was heat-sealed to obtain a liquid carbon dioxide gas indicator.

Using the obtained liquid carbon dioxide gas mixture, a package was prepared in the same manner as in Example 1, and in the same manner, the concentration of carbon dioxide present in the space inside the chemical solution container and the pH of the chemical solution were measured. The color change of the carbon dioxide gas indicator was observed. The results obtained are shown in Table 5 below. Table 5

As is evident from Table 5, the concentration of carbon dioxide in the drug solution container gradually decreased over time, and reached about 0.1% 6 hours after opening the package. The pH of the drug solution at that time was 8.1. In contrast, the color tone of the carbon dioxide gas indicator was yellow immediately after opening, turned brown 2 hours later, and turned blue 6 hours later. From this, it is clear that the carbon dioxide indicator used in the method of the present invention can change the color tone well reflecting the change in the concentration of carbon dioxide and the pH of the chemical solution in the chemical solution container. That is, when the indicia is yellow to brown, the pH of the chemical is 7.7 to 8.0, and it can be determined that the chemical is sufficiently usable. When the indicator is blue, the pH of the chemical is 8.1 or higher, and it can be determined that the chemical cannot be immediately applied or that the crane is no longer a dragon.

Comparative Example 2

A liquid carbon dioxide gas indicator was similarly prepared using LLDPE (thickness 60 iim, carbon dioxide gas permeability 6900 mLJm ² '24 hours) instead of the laminated film composed of LLDPE COC / LLDPE used as the surface layer in Example 2. Obtained.

Using the obtained liquid carbon dioxide gas indicator, a solid was prepared in the same manner as in Example 2, and immediately after opening and after a fixed time, similarly, the concentration of the carbon dioxide in the space inside the drug and the drug solution were similarly measured. The pH and pH of the mixture were measured, and the color change was observed over the course of carbon dioxide gas. Note that the measurement and dissatisfaction times are slightly different from those of Male Example 2. The results obtained are shown in Table 6 below. Table 6

As shown in Table 6, in Comparative Example 2, the color tone of the carbon dioxide gas indicator turned blue in 2 hours. However, in the past two hours, the pH of the chemical solution is 7.9, and 1.0% of carbon dioxide still remains in the chemical solution container, and the chemical solution can still be used sufficiently. That is, according to Comparative Example 1, the color tone of the carbon dioxide gas indicator has already changed to blue even when the chemical solution can still be used, and the color tone of the carbon dioxide gas indicator near PH8.1 at which the chemical solution cannot be actually used is changed. It does not change. Therefore, in this example, it is clear that it is not possible to judge the deterioration of the chemical solution due to the color change of the carbon dioxide gas.

Example 3

An ink composition having the same composition as the ink composition described in Example 1 was finely dispersed with a paint conditioner, and was used for analysis as ¾ ^. An ink layer as an indicator was formed by applying a coating having a thickness of 1 m and drying at 70 for 1 hour.

The obtained filter paper having a printing layer was stretched with polypropylene (OPP) (20 m thick (manufactured by Mitsui Chemicals, Inc., "B355J"), polyvinyl alcohol (PVA) (thickness m (manufactured by Synthetic Rubber Co., Ltd .: " Boblon ") and LLDPE (thickness 20 ^ m) sandwiched between two laminated films (carbon dioxide permeability 490m m2'24 hours), sealed in four sides of the film and in a bag (2x2cm2) On the other hand, a bicarbonate-containing chemical solution having the following formulation and pH was stored in a 400 m thick low-density polyethylene ampoule container as a chemical solution container (approximately 40 cc). The resulting ampule was sterilized with a hot water shower.

<Prescription of bicarbonate-containing drug solution> 7g sodium hydrogen carbonate

93g water

pH 7.9

The chemical contained in this ampoule can be safely used as a bicarbonate chemical when the pH is in the range of 7.9 to 8.6.

Then, the carbon dioxide gas indicator was attached to the surface of the ampoule container using Toyo Motor Corporation ΓΑΟ, ΓΑΟ-393 / TCSj as ^^, and the obtained container was weighed to a thickness of 12 m. Carbon vapor-deposited polyester film having a thickness of 12 m, polyester film having a thickness of 12 m, and a laminated film of carbon dioxide barrier composed of LLDPE having a thickness of 25 mm (carbon dioxide permeability: 0.3 m2'24 hours) The package was replaced with a mixed gas consisting of 50% by volume of carbon dioxide and 50% by volume of empty, and packaged to obtain a package with carbon dioxide replacement.

A total of seven identical packages were created and opened at the same time, and immediately after opening, one day, two days, three days, four days, five days, and six days, the ampoules contained in each package Measures the concentration of carbon dioxide present in the container and the pH of the drug solution in the container, and changes the color tone of the carbon dioxide gas pasted together! I did. Table 7 shows the obtained results.

As is clear from Table 7, the carbon dioxide gas concentration in the ampoule gradually decreased over time, and dropped to 5.0% five days after opening the package. The pH of the drug solution at that time was 8.6. Correspondingly, the color tone of CO2 Indigo changed from yellow immediately after opening to brown 3 days later and blue 5 days later. From this, when the pH of the chemical is 8.1 to 8.5, and when the chemical is sufficiently usable, the color tone of the carbon dioxide gas indicator is yellow or brown, and the pH of the chemical becomes 8.6, which is dangerous. It was found that the color tone of the carbon dioxide gas indicator turned blue when it was in the state. That is, in this example, it was clarified that the deterioration of the chemical solution after opening the package was indicated by the change in the color tone of carbon dioxide gas.

Comparative Example 3

In Example 3, a perforated polyethylene bag (2x2 cm ² , the permeability of which cannot be measured because the atmosphere can freely enter and exit) was used instead of the bag made of the OPP / PVA LLDPE laminated film. In the same way, a carbon dioxide indigo was obtained. Using the obtained carbon dioxide gas mixture, seven packages were prepared in the same manner as in Example 3, and the carbon dioxide gas in the chemical solution container immediately after opening and after a predetermined time had elapsed in the same manner as in Example 3. The concentration and the pH of the drug solution were measured, and the color tone change was observed over a night of carbon dioxide gas. However, the time for the measurement and the observation was set to a predetermined time of 5 hours or less because the color tone of the carbon dioxide gas indicator changed very quickly unlike Example 3. Table 8 shows the obtained results.

Table 8

In Comparative Example 3, the color tone of the carbon dioxide gas indicator changed to blue in 4 hours, but the pH of the drug solution after 4 hours remained at 8.1 (the release of carbon dioxide gas was very slow). To happen). In other words, in this example, the color change of the carbon dioxide gas indicator has already been completed before the chemical solution changes quality.Therefore, in the use of the carbon dioxide gas indicator, the period during which the chemical solution can be used safely is indicated by the color tone change. I can't do that.

Example 4

The same amounts of the same components as those of the ink composition shown in Example 1 were finely dispersed in a crystal cell opening of 10 g to obtain a powdered ink composition. 10 g of the obtained powder was the same laminated film as the laminated film described in Example 3.

(2x2cm2) sandwiched between the two sheets, and sealed the film on all sides to obtain a carbonic acid gas indigo.

Using the obtained carbon dioxide indicator, seven packages were prepared in the same manner as in Example 3, and the carbon dioxide concentration in the chemical solution container and the pH of the chemical solution were measured in the same manner as in Example 3. The change in the color tone of the carbon dioxide gas indicator was observed.

Table 9 shows the obtained results.

Table 9

As is evident from Table 9, the carbon dioxide gas concentration in the ampoule gradually decreased over time, and dropped to 5.0% five days after opening the package. The pH of the drug solution at that time was 8.6. Correspondingly, the color tone of the carbon dioxide indicator changed from yellow immediately after opening to brown after 3 days and blue after 5 days. From this, the pH of the chemical is 8. "! To 8.5. Therefore, when the chemical is sufficiently usable, the color tone of the carbon dioxide gas indicator is yellow and brown, and the pH of the chemical is 8.6 or higher and the use It was found that the color of the charcoal indicator changed to blue when it was in a dangerous state, that is, in this embodiment, the deterioration of the chemical solution after opening the package was indicated by the color change of the carbon dioxide gas indicator. · It became clear that we could confirm.

Comparative Example 4

Instead of using the same laminated film (2x2 cm2) as the laminated film described in Example 3 used in Example 4, a perforated polyethylene bag identical to the perforated polyethylene bag described in Comparative Example 3 was used. In the same manner, a carbon dioxide gas indicator was obtained.

Using the obtained carbon dioxide gas mixture, seven packages were prepared in the same manner as in Example 4, and in the same manner as in Example 4, the charcoal in the chemical solution container immediately after opening and after the elapse of the ^? The acid gas concentration and the pH of the drug solution were measured, and the color tone change was observed over the course of carbon dioxide gas. However, the time for measurement and observation was set to a predetermined time of 8 hours or less because the color tone of carbon dioxide gas changes relatively quickly compared to Example 4. Table 10 shows the obtained results.

Table 10

In Comparative Example 4, the color tone of the carbon dioxide gas indicator turned blue in 6 hours, whereas the pH of the drug solution after 6 hours remained at 8.1 (the release of carbon dioxide gas was gradual). To happen). In other words, in this example, the carbon dioxide gas indicator has already changed its color before the chemical solution changes its quality.Therefore, in the use of this carbon dioxide indicator, the period during which the chemical solution can be used safely cannot be indicated by the color change. Was found.

As described above in detail, in the method of the present invention, by utilizing the change in the color tone of the carbon dioxide gas indicator, after opening the package that has been subjected to the carbon dioxide replacement packaging, the contents contained in the package are deteriorated until the contents thereof change. · You can tell the time.

Example 5

Using the ink composition for detecting carbon dioxide described in Example 1-8, a printed layer (indicating portion) was formed in the same manner as in Example 1, and the surface was formed on the printed layer in the same manner as in Example 1. The layers were formed to create a carbon dioxide gas indicator.

By using each of the obtained carbon dioxide gas overnights to prepare a carbon dioxide-packaged package in the same manner as in Example 1, after opening the package, the contents (bicarbonate) The time at which the contained chemical solution is altered can be indicated by the change in color tone of the carbon dioxide gas indicator.

Claims

The scope of the claims

1. This is a method of indicating the deterioration of the content of carbon dioxide-replaced package after opening the package, and a carbon dioxide gas indicator that is coated with a pH indicator with a carbon dioxide permeable sound together with the content inside the package. A method of indicating the time when the contents are conditioned after opening the package by changing the color tone of the carbon dioxide gas.

2. The method according to claim 1, wherein the color change of the carbon dioxide indicator is caused by the release of carbon dioxide from inside the indicator.

3. The carbon dioxide permeable member has a carbon dioxide gas permeability of 50 to 20,000 mL within a range of 7 m ² .24 hours. By adjusting the carbon dioxide gas permeability, the release rate of carbon dioxide gas from within the carbon dioxide gas tank is controlled. 3. The method according to claim 2, wherein the time for changing the contents after opening the package is matched with the time for changing the color tone of the carbon dioxide indicator.

4. The method according to claim 1, wherein the content is a bicarbonate-containing chemical solution contained in a plastic pharmaceutical TO container having carbon dioxide gas permeability.

5. The method according to claim 4, wherein the drug solution container is a multi-chamber container having two or more storage chambers each capable of independently storing a drug solution, and having a partition wall capable of communicating between adjacent chambers.

6. The bicarbonate-containing chemical is selected from the group consisting of a solution containing sodium bicarbonate and sodium chloride contained in the first compartment, and a magnesium sulfate and magnesium chloride contained in the second compartment. The method according to claim 5, which is a solution containing at least one kind and glucose.

7. The method according to claim 5, wherein the bicarbonate-containing drug solution is a solution containing sodium bicarbonate and citric acid stored in the first chamber, and a solution containing oxyglutathione stored in the second chamber. The described method.

8. The method according to claim 1, wherein the pH indicator is in one form selected from the group consisting of a liquid, a solid, and a printed layer.

9. The method according to claim 8, wherein the printing layer is formed on a support using a carbon dioxide sensing ink composition containing a pH indicator, a binder and a solvent.

10. The method according to claim 9, wherein the support is a part of a chemical solution container or a support sheet that can be attached to the chemical solution container.

11. The method according to claim 9, wherein the carbon dioxide detection ink composition further comprises at least one selected from the group consisting of a water absorbing agent and an alkaline substance.

12. A carbon dioxide indicator used in the method according to claim 1.

13. A package obtained by using the carbon dioxide indicator according to claim 12, which is capable of indicating deterioration of the packaged contents after opening the package.

14. A carbon dioxide sensing ink composition for the carbon dioxide indicator according to claim 12, comprising a pH indicator, a binder and a solvent.

15. Use of the method according to claim 1 for carbon dioxide gassing according to claim 12.

16. Use of the ink composition for detecting carbon dioxide gas according to claim 14 for producing the carbon dioxide gas indicator according to claim 12.