JP2000308669A - Packaged material for container of chemical containing bicarbonate - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a packaged material for a chemical containing bicarbonate provided with a pin hole detecting agent capable of easily and visually checking a trouble of generation of pin holes in a secondary packaged material. SOLUTION: In the packaged material for a container of a chemical containing bicarbonate in which a gas permeable plastic container 2 in which a chemical 1 containing bicarbonate is sealed is packaged by a gas impermeable plastic packaging material 3, a space part 4 between the container 2 and the packaging material 3 is a carbon dioxide atmosphere, and a pin hole detecting agent 5 in which a specified pH indicator is sealed in a small gas permeable plastic container is arranged in the space part 4.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a package containing a bicarbonate-containing drug solution, more specifically, a plastic container containing an aqueous pharmaceutical solution containing a bicarbonate such as sodium bicarbonate, and the like. A carbonate-containing chemical liquid container package, wherein when a pinhole is generated in the packaging material of the package and the gas barrier property is reduced or disappears, the pinhole can be visually confirmed from outside the package by a color change. The present invention relates to an improved medicine container package provided with a detection agent.

[0002]

2. Description of the Related Art Bicarbonate-containing drug solutions, that is, medical aqueous solutions containing bicarbonate ions, include, for example, antidote, artificial kidney dialysate, peritoneal dialysate, infusion, root canal enlargement (dental), artificial marrow Fluid, intraocular perfusion solution, heart perfusion solution, myocardial protection solution, peritoneal lavage solution, organ preservation solution and the like. In such a pharmaceutical aqueous solution, bicarbonate ion is represented by the following formula (1)

[0003]

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In an open system, the reaction proceeds to the right due to the volatilization of carbon dioxide gas on the right side of the above formula (1), whereby the bicarbonate ion decreases and the carbonate ion An increase occurs and the pH of the aqueous solution gradually increases.

[0005] This change over time significantly reduces the value of the aqueous solution, considering that one of the main purposes of using the drug solution is to maintain or correct the acid-base equilibrium of the body fluid. In particular, it is known that injection of a solution having an increased carbonate ion causes necrosis of subcutaneous tissue (Howlan).
d, J. and Marriot, WM, Am. J. Dis.Child., 11 , 3
09 (1916), etc.], due to this adverse effect, the pH of sodium bicarbonate injection was adjusted to 7.9 to 7.9 in Japanese Pharmacopoeia XIII.
The carbonate ion concentration is regulated in the range of 8.6 and in the range of 7.0 to 8.5 in USP23.

[0006] Conventionally, such a pharmaceutical aqueous solution has been used, for example, in a glass ampoule,
The container is filled in a closed container such as a glass bottle and the like, and volatilization of generated carbon dioxide gas is prevented to maintain a certain equilibrium state, thereby stabilizing the hydrogen carbonate ion concentration and the liquid pH.

[0007] However, the glass container has a fatal disadvantage that it is easily broken, has difficulty in increasing its capacity, is very heavy, and has a hard time in disposal. Inevitably, the generation of carbon dioxide gas is unavoidable, and the generated gas increases the internal pressure of the container, which often causes damage to the glass container.

[0008] In recent years, various plastic containers have been studied as medical devices for solving the problem of breakage and the like seen in the above-mentioned glass containers, achieving lighter weight, and having good disposability. Various containers made of polyethylene, ethylene-vinyl acetate copolymer, polypropylene, polyvinyl chloride, etc. have been developed, but each of them alone has a large gas permeability of the material itself, and When the medical aqueous solution containing the bicarbonate ion is contained in a container, the generated carbon dioxide gas evaporates over time through the container wall into the atmosphere, and it is inevitable that the liquid pH rises. With the use of plastic containers, the disadvantages associated with the above-mentioned changes over time cannot be avoided. Further, the volatilization of carbon dioxide gas during sterilization and the accompanying increase in the pH of the solution also caused the same drawbacks.

In order to solve the drawbacks of the plastic container, the container is housed or packaged in a gas-impermeable secondary container (outer container or packaging container), and the space between the container and the outer container is carbonated. Techniques for producing a gas atmosphere have been developed (for example, Japanese Patent Application Laid-Open Nos. 5-49675 and 5-261).
141, JP-A-6-339512, etc.).

[0010] However, even in such a double packaging technique, there is probably a risk that slow gas permeation may occur due to the occurrence of pinholes or long-term storage of the secondary packaging material, thereby increasing the pH over time. The aqueous solution should be disposed of immediately with the danger,
It should not be accidentally administered to patients.

Various studies have been made on means for detecting the pH abnormality of such a double-packed bicarbonate-containing chemical solution, particularly the occurrence of pinholes which cause the pH abnormality. For example, Ageless (Mitsubishi Gas) is contained in a secondary package. An oxygen absorber such as Chemical Co., Ltd.) and an oxygen detector such as Ageless Eye (Mitsubishi Gas Chemical Co., Ltd.) are sealed to make it oxygen-free, and oxygen enters from outside due to pinholes. For example, a method of detecting this has been attempted. However, this method does not directly indicate a change in pH, but can only detect the case where oxygen enters from outside such as when a pinhole is generated. However, there is a drawback that a special operation is required so as not to contact oxygen and the like, and there is a need in the art to develop a technology for detecting pinholes without such a drawback.

[0012]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to eliminate all the drawbacks found in the above prior art, and to provide a container packaging body in which a plastic container containing a bicarbonate-containing chemical is packaged. It is an object of the present invention to provide a new chemical liquid container package that can reliably determine the occurrence of holes by visual inspection.

[0013]

Means for Solving the Problems As a result of intensive studies from the above-mentioned object, the present inventors have sealed a bicarbonate-containing chemical solution in a gas-permeable plastic container, and then filled the container with a high-pressure steam according to a conventional method. Sterilize by sterilization, hot water immersion sterilization, hot water shower sterilization, or the like, or aseptically enclose a chemical solution containing bicarbonate in a plastic container, and then place the resulting container in a gas-impermeable plastic packaging material. The space between the container and the packaging material is carbon dioxide gas atmosphere, and an aqueous solution or an organic solvent solution of a pH indicator having an acid-to-neutral discoloration region in the space is gas-permeable plastic. When arranging a pinhole detection agent sealed in a small container, it has been found that a new chemical liquid container package meeting the above object can be provided, and the present invention has been completed.

That is, according to the present invention, in a bicarbonate-containing chemical container package, a gas-permeable plastic container enclosing a bicarbonate-containing chemical is packaged with a gas-impermeable plastic packaging material. The space between the container and the packaging material is a carbon dioxide gas atmosphere, and a pinhole detecting agent is disposed in the space, and the pinhole detecting agent has a color change range from acidic to neutral. A bicarbonate-containing chemical liquid container package is provided in which an aqueous solution of an indicator or an organic solvent solution is sealed in a small gas-permeable plastic container.

In particular, according to the present invention, the pH indicator is p
A bicarbonate-containing chemical container package having a discoloration range in H3 to H7 and a chemical container package in which the pH indicator is Congo Red are provided.

Preferred embodiments of the bicarbonate-containing chemical liquid container package according to the present invention include the following. (1) Those having a pH indicator concentration of 10 to 2000 ppm. (2) The bicarbonate is sodium bicarbonate. (3) A carbon dioxide atmosphere is formed in the space by utilizing a carbon dioxide-generating type oxygen absorbent or filling a mixed gas containing carbon dioxide.

The container package of the present invention, by adopting the above structure, has the advantages of being less likely to be damaged due to the use of a plastic container, of being easy to increase in capacity and of being lighter in weight, and a gas-impermeable secondary packaging material. Of course, the advantage of preventing the volatilization of carbon dioxide generated from the chemical solution into the atmosphere and maintaining the pH value of the chemical solution at a constant value based on the use of the carbon dioxide gas atmosphere in the space portion is guaranteed. In addition, there is an advantage that the pH change of the drug solution due to the generation of pinholes in the secondary packaging material and the accompanying deterioration can be easily visually confirmed, and can be easily manufactured by ordinary operations.

[0018]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the container package of the present invention will be described in detail. In the present invention, the chemical solution containing bicarbonate includes sodium bicarbonate, ammonium bicarbonate,
Potassium bicarbonate, other aqueous solution of bicarbonate alone or an aqueous solution composed of each salt and other components, etc., which produces bicarbonate ion, and carbonates which produce carbonate ion such as sodium carbonate, potassium carbonate, etc. Aqueous solution and the like can be exemplified (even if added as a carbonate, it becomes a bicarbonate at the pH used). Although the bicarbonate ion concentration of each aqueous solution is not particularly limited, it is usually in the range of about 0.01 to 1 M, which is about 0.01 to 1 M of the bicarbonate aqueous solution. About 10%. As a particularly preferable bicarbonate concentration, a range of about 0.1 to 8.5% can be exemplified.

The composition of the bicarbonate-containing drug solution can be appropriately determined according to the intended use of the drug solution, and is not limited. The conventionally known antidote, artificial kidney dialysis solution,
Peritoneal dialysis fluid, infusion, root canal enlarger (for dental use), artificial cerebrospinal fluid,
The composition of the intraocular perfusion solution, the heart perfusion solution, the cardioplegic solution, the peritoneal lavage solution, the organ preservation solution and the like may be the same, or these may be slightly changed.

One typical bicarbonate-containing chemical solution contains electrolyte ions and reducing sugars in the following composition ranges:
In addition, it may contain, for example, phosphate ions or ions of trace metals such as copper and zinc. Sodium ion 120-170 mEq / l potassium ion 0-10 mEq / l calcium ion 2-5 mEq / l magnesium ion 0-3 mEq / l chloride ion 100-150 mEq / l bicarbonate ion 15-40 mEq / l reducing sugar 0-10 w / v % As the gas-permeable plastic container for enclosing (accommodating and filling) the drug solution, any of various types of containers conventionally used in the medical field can be used. Specific examples thereof include those made of polyethylene, ethylene-vinyl acetate copolymer, polypropylene, polyvinyl chloride, and those obtained by blending or laminating them at an appropriate ratio. The shape and size of the container are not particularly limited, but generally rectangular or cylindrical containers are often used, and their contents generally range from about 20 ml to about 3 l. It is preferable to use such a container also in the present invention.

Further, the container may be a gas-permeable plastic bag comprising at least two chambers having a partition which can communicate with each other. Such a bag is already known, for example, provided with a means for closing a communication section of two chambers (Japanese Patent Publication No. Sho 63-20550, Japanese Utility Model Publication No. Sho 63-205).
(See Japanese Patent Application Laid-Open No. Sho. 63-17926) and a seal part which partitions two chambers can be communicated by pressing.
3 and JP-A-2-4671). In these bags, at least one
It is sufficient that the bicarbonate-containing chemical solution is sealed in the chamber.

The term "gas-impermeable" in a gas-impermeable packaging material does not mean that gas is not strictly permeable, but means that the gas-impermeable property is larger than that of the above-mentioned chemical solution container. This can be used as a gas-impermeable packaging material according to the present invention when the same material as the above-mentioned chemical solution container is used but the thickness is large. As the material of such a gas-impermeable wrapping material, for example, polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polyvinyl alcohol (PVA), ethylene-vinyl alcohol copolymer, which is generally used widely as such a wrapping material, is used. (EVOH), polyvinylidene chloride (PVDC), nylon, etc., materials such as silicon oxide, aluminum oxide, etc. deposited on the surface of these materials, and multilayer films (laminated films) of these materials ) Can be exemplified. The shape, size, etc. of the packaging material are not particularly limited on the premise that the plastic container can be accommodated, but after this accommodation, a sufficient space for enclosing a carbon dioxide-containing gas with the container is required. It is necessary to have a shape and size that can be formed. Generally, it is desirable that the size is about 1.2 to 3 times the capacity of the plastic container.

As means for setting the space between the container and the packaging material to a carbon dioxide atmosphere, for example, first, a carbon dioxide gas such as a mixed gas of carbon dioxide and air or a mixed gas of carbon dioxide and nitrogen gas is used. A method of enclosing a mixed gas containing a gas in the space can be adopted. In this method, the carbon dioxide concentration of the mixed gas used is appropriately determined according to the type of the chemical solution filled in the plastic container, particularly the hydrogen carbonate ion concentration and the pH. For example, when an aqueous solution in which 70 g of sodium hydrogen carbonate is dissolved in water for injection to make the total volume 1 liter is selected as the above-mentioned chemical solution, the aqueous solution has a hydrogen carbonate ion concentration of 833 mM and a pH of 8.2, and holds this value. For this purpose, the concentration of carbon dioxide in the mixed gas atmosphere is preferably about 40%.

In the present invention, the bicarbonate ion concentration and pH of the chemical solution are generally about 0.01 to 1M and 6.5 to 6.5M.
It is about 8.6, and the partial pressure of carbon dioxide in the space is preferably adjusted to a range of about 1 mmHg to 760 mmHg. According to this, it is necessary to select the content ratio of carbon dioxide in the mixed gas. preferable. More specifically, when the pH of the chemical solution after manufacture is within a predetermined range, the carbon dioxide gas sealed in the space may be made substantially equal to the carbon dioxide partial pressure of the chemical solution.

As another means for setting the space between the container and the packaging material to a carbon dioxide gas atmosphere, for example, oxygen gas existing in the space is absorbed and a certain volume of the gas is absorbed. Means for enclosing a carbon dioxide-generating type oxygen absorbent that releases carbon dioxide in the space may be used. Examples of the carbon dioxide-generating oxygen absorber include “Ageless G” and “Ageless GM” manufactured by Mitsubishi Gas Chemical Company, Inc., and a freshness retaining agent C type manufactured by Toppan Printing Co., Ltd.

According to the present invention, the filling of the drug solution into the container, the sterilization, the packaging with the packaging material, the carbon dioxide atmosphere in the space, and the like can be easily carried out according to the usual method for producing an injection solution.

The present invention has an essential requirement that a specific pinhole detecting agent is further disposed in the space of the bicarbonate-containing chemical liquid container package prepared as described above. Here, the pinhole detecting agent is characterized in that an aqueous solution or an organic solvent solution of a pH indicator having a discoloration range from acidic to neutral range is sealed in a small gas-permeable plastic container. By arranging and using this in the space between the container and the packaging material of the bicarbonate-containing drug container package of the present invention, leakage of carbon dioxide from the space can be indicated by a change in color tone. .

P used in the pinhole detecting agent
As the H indicator, from various acid / base indicators capable of indicating a change in pH of the detection agent of the present invention caused by a change in the presence (absorption, release) of carbon dioxide as a color tone change, particularly from an acidic region to a neutral region. Select one having a discoloration range.
The color tone of the pH indicator has a color on the low pH side of the acidic region when carbon dioxide gas is present, and the color on the high pH side or the neutral region of the acidic region when the gas leaks. Change to color.

Particularly preferred pH indicators are (1) a narrow discoloration area, (2) high color intensity, and (3)
The direction of discoloration is appropriate (from inconspicuous color to conspicuous color), (4) excellent hygiene (high safety of the substance itself, no migration), (5) good stability, It is preferable to select from those having properties such as maintaining the initial discoloration ability over a long period of time. Specific examples of such a pH indicator include, for example, Congo Red (color changes from blue to red at pH 3 to 5), bromophenol blue (pH
3-4.1, changing color from yellow to blue), methylene orange (color changing from red to yellow, pH 3-3.46), bromcresol green (color changing from yellow to blue at pH 4.2-4.9), methyl red (Color changes from red to yellow at pH 4.2-5), chlorophenol red (pH 5-6.2)
5 to discolor from yellow to red), bromcresol purple (discolor from yellow to purple at pH 5.2 to 6.4), bromthymol blue (discolor from yellow to blue at pH 6 to 7.3) and the like. Among them, the discoloration range is pH 3 ~
7 is preferable, and Congo Red is particularly preferable.

The above pH indicator is used in the form of an aqueous solution or an organic solvent solution. Here, as the organic solvent, for example, a mixed solvent of ethanol, methanol, acetone, and the like can be used. P in the prepared solution
The concentration of the H indicator is not particularly limited as long as the change in color tone is easy to visually observe. For example, the concentration of the H indicator is about 10 to 2000 ppm depending on the size of the small container in which the color tone is sealed (the thickness of the liquid layer).
Can be appropriately selected from the range.

In the above aqueous solution or organic solvent solution,
In order to adjust the pH, an appropriate acidic substance or alkaline substance can be blended. Examples of the acidic substance include inorganic acids such as phosphoric acid, hydrochloric acid, nitric acid, and sulfuric acid, and organic acids such as acetic acid and lactic acid. Examples of the alkaline substance include hydroxides, carbonates, bicarbonates, and phosphates of alkali metals or alkaline earth metals. These may be hydrated salts or anhydrous salts. More specifically, sodium borate, sodium hydroxide, sodium carbonate, lithium hydroxide, sodium hydrogen carbonate, sodium hydrogen phosphate, barium hydroxide, magnesium hydroxide and the like can be mentioned. Among them, sodium hydrogen carbonate, sodium hydrogen phosphate and sodium hydroxide are preferred. These acidic substances and alkaline substances can be used each alone or two or more of them can be used in combination.

The pinhole detecting agent of the present invention may optionally contain a humectant. The humectant may be any of various well-known ones. For example, glycerin, polyethylene glycol, propylene glycol and the like can be used alone or in combination of two or more. The blending amount is not particularly limited, but is usually 10% (w
/ V%, the same applies hereinafter). This addition and blending can prevent the solvent from evaporating, especially when an organic solvent solution is used. The lower limit of the amount of the humectant that can exert the above effects is usually about 0.1%.

The pinhole detecting agent of the present invention is prepared by enclosing an aqueous solution or an organic solvent solution (referred to as an internal solution) of the above-mentioned pH indicator and other additives in a small gas-permeable plastic container. Its preparation can be performed according to a conventional method. The material of the gas-permeable plastic container used at that time may be any material having a gas permeability equal to or higher than that of the above-mentioned chemical solution container. For example, the small container can be manufactured by a method in which bag making, filling, and sealing are continuously performed using a vertical three-side sealing machine, a vertical pillow packaging machine, a rotary packer, or the like. In the case of using such a method, the material of the small container is particularly preferably a laminated film from the viewpoint of machine suitability. In particular, when a polyethylene solution is used as the chemical liquid container, polypropylene (outside) and polyethylene (inside) are used. And a laminated film of poly-4-methyl-1-pentene (outside) and polyethylene (inside).

Regarding the size of the small container and the volume of the internal liquid, when the internal liquid is sealed in the small container, if the amount of the internal liquid is small, the thickness of the liquid layer of the indicator becomes too thin, and the color tone change is visually observed. Since there is a tendency that it is difficult to make a distinction, it is premised that this change in color tone can be easily distinguished visually, and it can be appropriately determined in consideration of the size of the chemical container and the secondary packaging material.

The pinhole detecting agent thus prepared is
Bacteria may grow in the internal solution during long-term storage to cause turbidity. To prevent or suppress this, high-pressure steam sterilization can be performed. In place of this, a bactericide such as benzalkonium chloride or chlorhexidine gluconate, an antibacterial agent such as nalidixic acid or norfloxacin, a preservative such as paraoxybenzoate or benzyl alcohol can be appropriately added and blended.

The pinhole detecting agent of the present invention is usually a clear one whose color tone change can be sufficiently visually confirmed.
Although not particularly essential, an appropriate dye may be appropriately added and blended in order to make the color tone change clearer.

In the pinhole detecting agent thus obtained, a carbon dioxide gas can be dissolved in advance by, for example, publishing or the like, and it is packaged together with a chemical solution container as described below, and the space is formed with a carbon dioxide gas atmosphere. If so, this results in a form in which carbon dioxide is naturally dissolved in the detection agent.

In arranging the pinhole detecting agent of the present invention in the space of the chemical liquid container package, the chemical liquid container and the pinhole detecting agent are simply packaged together in a secondary packaging with a gas barrier packaging material. Yes, its location is
There is no particular limitation as long as the pinhole detecting agent is visible from the outside even after packaging with the secondary packaging material. Thus, the intended drug solution container package of the present invention can be obtained.

A preferred embodiment of the chemical solution container package of the present invention is as shown in the attached drawing (FIG. 1), which comprises a plastic container 2 in which a chemical solution containing bicarbonate (content solution, 1) is enclosed. Gas-impermeable wrapping material 3 for packaging the container
And a pinhole detecting agent 5 disposed in a space 4 between the container and the packaging material, and the space is provided with a carbon dioxide gas-containing atmosphere. In addition to the effect of visually confirming the intended change in the pH of the drug solution, the various effects described above can be achieved.

[0040]

EXAMPLES Hereinafter, in order to explain the present invention in more detail, a production example of a pinhole detecting agent will be described, followed by an example of a drug solution container package of the present invention. Production Example 1 1 g of Congo Red was dissolved in 5 l of water to prepare an aqueous solution, and 2 ml of the aqueous solution was laminated with a vertical three-side sealing machine to a polypropylene (outside, thickness: 20 μm) / polyethylene (inside, thickness: 30 μm) laminate Encapsulated in film,
A pinhole detecting agent having a length of 30 mm and a width of 15 mm (inner size) was obtained. This was bubbled with carbon dioxide to prepare a purple pinhole detector of the present invention. Production Example 2 1 g of Congo Red was dissolved in 4.5 liters of ethanol and 0.5 liter of glycerin, and the pH was adjusted to about 3 by further dissolving carbon dioxide gas. (Thickness: 20 μm) / polyethylene (inside, thickness: 30 μm) was sealed in a laminated film to obtain a pinhole detecting agent of the present invention having a length of 30 mm and a width of 15 mm (inner size). The color of this pinhole detecting agent was purple. Example 1 500 ml of artificial cerebrospinal fluid having the composition shown in the following Table 1 packed in a polyethylene drug solution bag (average thickness: 250 μm) was subjected to high-pressure steam sterilization (pH after sterilization: 7.30), and then a pinhole prepared in Production Example 1 Replace with a mixed gas of 6% carbon dioxide + 94% air together with a detecting agent (6% carbon dioxide dissolved), nylon (thickness: 15 μm) / polyvinyl alcohol (thickness: 12 μm) / LLDPE ( (Thickness: 40 μm)
To obtain a package for a drug solution container of the present invention. Table 1. Chemical solution containing bicarbonate (/ ml) Sodium bicarbonate 1.94 mg Sodium chloride 7.24 mg Potassium chloride 0.05 mg Calcium chloride (dihydrate) 0.17 mg Magnesium chloride (hexahydrate) 0.23 mg Glucose 0. 6 mg monopotassium dihydrogen phosphate 0.15 mg citric acid (additive) 0.32 mg The pinhole detecting agent placed in the space of the container and packaging body of the present invention thus obtained was purple-red.

The secondary packaging material of the packaged product for a drug solution container of the present invention produced as described above is pinhole-filled with a syringe needle (27G, Terumo Corporation, Neoras) (major axis: about 500 μm, minor axis: about 50 μm).
m) was opened, and the discoloration of the pinhole detecting agent was observed. As a result, immediately after the pinhole was opened, the color was reddish purple, but 4
It was confirmed that the color changed to red after 8 hours. Example 2 In the same manner as in Example 1 except that the artificial cerebrospinal fluid was replaced with an electrolyte infusion prepared by the following method, a drug solution package of the present invention was obtained. [Preparation of Electrolyte Infusion Agent] Each component shown in Table 2 below was dissolved in distilled water for injection at room temperature, and a 0.3 M citric acid solution was added so that the final concentration was 3 mEq / l.
The volume was 0 ml. This solution was filtered through a membrane filter having a pore size of 0.22 μm, and the filtrate was placed in a glass container in an amount of 500 ml.
Each was filled and sealed. Then, the solution was subjected to high-pressure steam sterilization to obtain an intended infusion solution. Table 2 Component concentration (g / l) Sodium chloride 6.55 Potassium chloride 0.80 Sodium bicarbonate 2.36 Calcium chloride (trihydrate) 0.22 Magnesium sulfate (heptahydrate) 0.25 Book prepared above A pinhole (major axis: about 500 μm, minor axis: about 50 μm) was opened with a syringe needle (27G, Terumo Corp., Neoras) in the secondary packaging material of the product for a drug solution container package, and discoloration was observed. As a result, the pinhole detector was reddish purple at first, but turned red 48 hours later. Example 3 In Example 1, an intraocular perfusion solution prepared by the following method was used in place of the artificial cerebrospinal fluid, and prepared in Production Example 1 as a pinhole detecting agent, and dissolved in carbon dioxide gas to a concentration of 4%. In the same manner as above, a package for a drug solution container of the present invention was obtained. [Preparation of Intraocular Perfusion Solution] Each component shown in Table 3 below was dissolved in sterilized purified water, and 10 w / v% hydrochloric acid was added thereto to adjust the pH to 7.2.
Then, sterilized purified water was added until the total volume became 1000 ml, and sterilized under pressure to obtain an intended intraocular perfusion solution (osmotic pressure: 280 to 300 mOsm). Table 3 components (g) sodium chloride 6.60 potassium chloride 0.36 calcium chloride (dihydrate) 0.18 magnesium sulfate (heptahydrate) 0.30 sodium bicarbonate 2.10 sodium citrate (dihydrate) 1.00 Sodium acetate (trihydrate) 0.60 Glucose 1.50 A pinhole (long diameter) was added to the secondary packaging material of the drug solution container package product of the present invention prepared above using an injection needle (27G, Terumo Corporation, Neorus). (About 500 μm, short diameter about 50 μm) was opened, and the discoloration of the pinhole detecting agent was observed. As a result, it was confirmed that the color was reddish purple immediately after the pinhole was opened, but turned red after 48 hours. Example 4 A 7% sodium bicarbonate injection adjusted to pH 8.3 was prepared from low-density polyethylene (Ube Industries B-128H) 2
0ml plastic ampule (average thickness: 0.6mm)
And the pinhole detector obtained by dissolving 50% of carbon dioxide gas in Production Example 2 was mixed with polypropylene (200 μm) / ethylene-vinyl alcohol copolymer (100 μm) / polypropylene ( 200μ
m) and PET (12μ)
m) / polyvinyl alcohol (14 μm) / special polypropylene (40 μm) In a blister package consisting of a lid material which is a laminate film, the mixture is sealed with a mixed gas of 50% carbon dioxide + 50% air (space volume: 30 m)
1) to obtain a package of the drug solution container of the present invention.

The secondary wrapping material of the above-prepared drug solution container package product of the present invention was pinhole-filled with a syringe needle (27G, Terumo Corporation, Neoras) (major axis: about 500 μm, minor axis: about 50 μm).
m) was opened, and the discoloration of the pinhole detecting agent was observed. As a result, it was confirmed that the color was purple immediately after the pinhole was opened, but turned red after one hour.

[Brief description of the drawings]

FIG. 1 is a schematic view showing one embodiment of a package for a chemical solution container of the present invention.

[Explanation of symbols]

 (1) Chemical solution (2) Container made of gas-permeable plastic (3) Packaging material made of gas-impermeable plastic (4) Space between container 2 and packaging material 3 (5) Pinhole detector

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) B65D 77/04 G01N 31/22 123 G01M 3/20 A61J 1/00 333Z G01N 31/22 123 390S (72) Inventor Kohei Yuyama 961 Mitsuho, Matsumo-cho, Itano-gun, Tokushima Prefecture Otsuka Pharmaceutical Matsumo-ryo (72) Inventor Junji Kaga 11-1 Sannomiya, Ejiri-ji, Sannomiya, Kitajima-cho, Itano-gun, Tokushima Prefecture No. 28, Naniwa-shi, Naruto, Pref. EE21 EE47 FA04 GD10 4C077 AA05 AA06 AA25 BB01 DD12 GG09 HH07 HH20 KK21 KK30 PP08 PP09 PP12 PP13 PP18 PP24 PP26

Claims (3)

[Claims] 1. A bicarbonate-containing chemical liquid container package in which a gas-permeable plastic container enclosing a bicarbonate-containing chemical liquid is packaged with a gas-impermeable plastic packaging material. Is a carbon dioxide gas atmosphere, and a pinhole detector is disposed in the space, and the pinhole detector has an aqueous solution or an organic solvent of a pH indicator having a discoloration range from acidic to neutral range. A bicarbonate-containing chemical liquid container package, characterized in that the solution is sealed in a small gas-permeable plastic container. 2. The chemical liquid container package according to claim 1, wherein the pH indicator has a color change range of pH 3 to 7. 3. The chemical container package according to claim 2, wherein the pH indicator is Congo Red.