JP4018930B2 - Package with oxygen indicator function - Google Patents

Description

【００４１】
試験例２
インキ組成物を作製し、光と熱に対する安定性を調査した。試験例１と同様にして、アミノ酸輸液５００ｍＬを収容したポリエチレン製容器を実施例１および２で作製した本発明包装体の包装材で包装し、脱酸素剤エージレス（ＺＨ−１００Ｐ）を入れ、窒素置換後に密封し、無酸素状態として各条件下に保存した。
比較例として、ペーパーアイとアミノ酸輸液５００ｍＬを収容したポリエチレン製容器を比較例１および２で作製された包装材で包装し、脱酸素剤エージレス（ＺＨ−１００Ｐ）を入れ、窒素置換後に密封し、無酸素状態として各条件下に保存した。
【００４２】
（１）光安定性試験
太陽光の照射する窓ガラスに張り付けして保存し、色調の変化を調査した。結果を下記表に示す。
【表２】

【００４３】
比較例１および２では経時３日後に色調が不安定となったのに対し、実施例１および２では５日後も無酸素状態の色調の黄色を呈した。１４日後にガス非透過性包装材で包装された包装体を開封すると、実施例１および２では青色に戻ったが、比較例１および２では変色しなかった。
【００４４】
（２）安定性試験
４０℃、無酸素保存経時で色調の変化を調査した。結果を下記表に示す。
【表３】

【００４５】
比較例１および２では経時２ヵ月後に無酸素時に示す色調が不良となったのに対し、実施例１および２では３ヶ月後も無酸素状態の色調の黄色を呈した。３ヵ月後にガス非透過性包装材で包装された包装体を開封すると、実施例１および２では青色に戻ったが、比較例１および２では変色しなかった。
【００４６】
【発明の効果】
本発明によれば、外部から酸素検知部の変色が容易に確認でき、さらに、光安定性および変色速度の優れた酸素インジケーター機能付き包装体を得ることができる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a package for storing medicines, medicines, foods (including beverages) and the like for a long period of time. More specifically, the present invention relates to a package with an oxygen indicator function, characterized in that an oxygen detector is provided by printing.
[0002]
[Prior art]
Gas replacement packaging is a common method for preventing the oxidation of contents such as medicines, medicines and foods (including beverages) and storing them for a long period of time. In the gas replacement packaging, for example, nitrogen is used as a replacement gas and packaging is performed with a packaging material having excellent gas non-permeability. As described above, the contents can be stored for a long time by performing the gas replacement packaging using the packaging material having excellent gas non-permeability.
However, if a pinhole or seal failure occurs due to a defect in the packaging material itself, a failure in filling the contents, or an impact in the transportation process such as distribution, etc., the atmosphere in which the gas replacement packaging is performed changes. However, the contents may be spoiled or deteriorated, and there is a risk that the contents may be distributed without being aware of the change in the atmosphere of the gas replacement package.
In this way, there is no means for confirming pinholes, seal defects, etc., even when gas replacement packaging is performed using packaging materials with excellent gas impermeability, and the contents are reliably stored in the gas replacement packaging atmosphere. I didn't know if it was.
[0003]
Therefore, in order to improve the above problems, a package containing an oxygen indicator that changes its hue depending on the presence or absence of oxygen has been developed.
Conventionally, as an oxygen indicator, tablets are individually packaged, medicines or foods are shielded from external oxygen, packaged in gas-impermeable film sachets, and the packaged tablets are put into the package. Thus, the presence or absence of oxygen is determined. However, in the conventional tablet, (1) the tablets must be individually packaged, (2) when the tablets disintegrate, the disintegrated powder flows out through the holes opened in the sachets. 3) Various drugs such as drugs that lead to malpractice due to accidental ingestion of tablets, (4) it is difficult to fix the tablets in the package, (5) tablets move within the package, and are difficult to visually detect from the outside. Had problems.
[0004]
[Problems to be solved by the invention]
It is an object of the present invention to provide a package with an oxygen indicator function that can easily check a change in gas atmosphere in the package due to occurrence of pinholes, poor seals, etc. in a package having a deoxygenated atmosphere.
[0005]
[Means for Solving the Problems]
As a result of intensive studies to solve the above problems, the present inventors have wrapped a gas permeable container containing a drug or food that is easily altered by oxygen with a gas non-permeable packaging material, and printed the oxygen detector by printing. It has been found that the above-mentioned problems can be solved at once by using the package with an oxygen indicator function provided, and further studies have been made to complete the present invention.
[0006]
That is, the present invention
(1) A gas permeable container containing a drug or food that is easily altered by oxygen is packed in a gas impermeable packaging material, and the package is deoxygenated by gas replacement, vacuum, or an oxygen scavenger. A packaging body with an oxygen indicator function, characterized in that, in the packaging body having an atmosphere, an oxygen detection unit for detecting a gas atmosphere change of the packaging body due to a defect of the packaging material by color tone change is provided by printing,
(2) One or more selected from the group consisting of amino acid drug solutions, carbohydrate drug solutions, vitamin-containing drug solutions, bicarbonate drug solutions, fat emulsions, and antibiotic preparations, which are easily altered by oxygen A package with an oxygen indicator function according to (1) above,
(3) The package with an oxygen indicator function according to (1) or (2) above, wherein the drug or food that is easily altered by oxygen is a glycyrrhizin preparation,
(4) Any of (1) to (3) above, wherein the oxygen detector is a coating film formed by an ink composition containing an aqueous solution or organic solvent solution containing a reducing substance and a pH indicator. Packaging with oxygen indicator function as described in
(5) The package with an oxygen indicator function according to (4), wherein the reducing substance is a reducing amino acid, a reducing vitamin, or a reducing saccharide,
(6) The packaging with an oxygen indicator function according to (4) or (5), wherein the reducing substance is cysteine or cystine, and the pH indicator is a thiazine dye and / or an indigo dye body,
(7) The package with an oxygen indicator function according to (6) above, wherein the concentration of cysteines or cystines is 100 to 100,000 ppm,
(8) Cysteine or cystine is L-cysteine, L-cysteine hydrochloride, DL-cysteine, DL-cysteine hydrochloride, D-cysteine, D-cysteine hydrochloride, L-ethylcysteine hydrochloride, L-methylcysteine hydrochloride The oxygen indicator function according to (6) or (7), wherein the oxygen indicator function is one or more selected from the group consisting of acetylcysteine, S-carboxymethyl-L-cysteine, and L-cystine Packaging,
(9) The package with an oxygen indicator function according to (6) above, wherein the concentration of the thiazine dye and / or the indigo dye is 100 to 100,000 ppm,
(10) Thiazine dye or indigo dye is from Ultra Violet, Azure C, Azure B, Methylene Blue, Methionine Blue, New Methylene Blue, Methylene Green, Rous Violet, Neomethylene Blue, Brilliant Alizarin Blue, Indigo, Indigo Carmine, Bromine Indigo R A package with an oxygen indicator function according to (6) or (9), wherein the package is one or more selected from the group consisting of:
(11) The package with an oxygen indicator function according to any one of (1) to (10), wherein printing is displayed on the outside of the gas permeable container or on the inside of the gas impermeable packaging material. ,
(12) The package with an oxygen indicator function according to any one of (1) to (11), wherein the oxygen detector is a pinhole detector,
(13) A pharmaceutical or food that is easily altered by oxygen stored in a gas-permeable container of the package with an oxygen indicator function according to any one of (1) to (12),
(14) Oxygen characterized by being stored and stored in a gas-permeable container of a package with an oxygen indicator function according to any one of (1) to (12) above, which is easily altered by oxygen. A method for preserving medicines or foods that are easily altered
About.
[0007]
DETAILED DESCRIPTION OF THE INVENTION
The package with an oxygen indicator function of the present invention is characterized in that an oxygen detector is provided by printing. The oxygen detector is preferably a coating film formed by printing the ink composition on a gas permeable container or a gas non-permeable packaging material. The oxygen detector is preferably a pinhole detector.
This ink composition changes its color tone when oxygen is present in the package atmosphere. By visually observing the change in color tone from the outside of the package, it is possible to judge the change in oxygen concentration in the atmosphere in the package based on the color tone of the oxygen detector, and to easily generate pinholes and defective seals in the package. Can be confirmed.
[0008]
The ink composition is preferably composed of a reducing substance, a pH indicator, a solvent, a binder, moisture and the like.
[0009]
Although it does not specifically limit as a reducing substance, Preferably, for example, reducing amino acids, reducing vitamins, reducing saccharides, etc. are mentioned. Examples of reducing amino acids include cysteines and cystines. Examples of reducing vitamins include vitamin E, vitamin A, and vitamin C. Examples of reducing sugars include monosaccharides such as glucose, fructose, galactose, xylose and mannose, disaccharides such as maltose, lactose and cellobiose, and trisaccharides such as maltotriose, cellotriose and manninotriose. Furthermore, isomerized sugar obtained by allowing isomerase to act on glucose, and a mixture of starch syrup obtained by hydrolyzing starch with acid or enzyme, and the like are also included.
[0010]
As the reducing substance, cysteines or cystines are preferably used. As the cysteines or cystines, any of L-form, DL-form, and D-form can be used. In addition to L-form, DL-form, and D-form, salts thereof, esters, N-acyl derivatives, and the like can also be used. Examples of the salts include hydrochloride. Examples of the ester include alkyl esters such as methyl ester and ethyl ester. Examples of N-acyl derivatives include acetyl derivatives and benzoyl derivatives. Specific examples of these cysteines and cystines include, for example, L-cysteine, L-cysteine hydrochloride, DL-cysteine, DL-cysteine hydrochloride, D-cysteine, D-cysteine hydrochloride, and L-ethylcysteine hydrochloride. , Hydrochloric acid, L-methylcysteine, acetylcysteine, S-carboxymethyl-L-cysteine, L-cystine and the like. These can be used alone or in combination of two or more. In addition to being stable to heat and light, cysteines or cystines have an unprecedented strong reducing ability, so that it is possible to increase the blending ratio of the pH indicator described below.
[0011]
For example, the concentration of the reducing substance such as cysteines or cystines is not particularly limited, but is preferably in the range of about 100 to about 100,000 ppm.
[0012]
The pH indicator is preferably one that can be easily visually checked for changes in color tone. For example, methylene blue, leucomethylene blue, 2,6-dichlorophenolindophenol, methylphenazonium metasulfate, cresol violet, pyocyanin, resazurin, indigo, m-cresol purple, thymol blue, cresol red, phenolphthalein, bromothymol Blue, phenol red, dibromophenol tetrabrom, methylthymol blue, alizarin, xylitol orange, bromophenol red, congo red, sodium alizarin sulfonate, neutral red, safranin T, phenosafranine, capri blue, nile blue, diphenylamine, xylene Cyanol, nitrodiphenylamine, ferroin, N-phenylanthranilic acid, etc. Kill. More preferable examples include thiazine dyes such as methylene blue, and indigo dyes such as indigo.
[0013]
As the thiazine dye and indigo dye, a dye in which the color tone in the presence of oxygen changes to colorless or other color tone in an oxygen-free state is preferable. Examples of thiazine dyes include, for example, ultra violet, Azure C, Azure B, methylene blue, methionine blue, new methylene blue, methylene green, rous violet, neomethylene blue, brilliant alizarin blue and the like. Examples of indigo dyes include indigo, indigo carmine, bromoindigo R, and the like. These pigments may be used alone or in combination of two or more.
[0014]
For example, the concentration of pH indicators such as thiazine dyes and indigo dyes is not particularly limited, but is preferably in the range of about 100 to about 100,000 ppm.
[0015]
In addition, in order to make the change in hue due to the presence or absence of oxygen even more clear, regardless of the presence or absence of oxygen, ordinary pigments, pigments, dyes and the like that do not change the hue. It can also be used together.
[0016]
The ratio of use of the pH indicator such as the thiazine dye and / or indigo dye and the reducing substance such as cysteines or cystines is not particularly limited, but is usually reduced such as cysteines or cystines. The pH indicator such as thiazine dye and / or indigo dye may be in the range of about 1/1000 to about 1000 parts by weight, preferably about 1/10 to about 10 parts by weight with respect to 100 parts by weight of the active substance.
In addition, as a combination of a reducing substance and a pH indicator, Preferably, cysteine or its salt (especially hydrochloride) is used as a reducing substance, and methylene blue is used as a pH indicator.
[0017]
The solvent is preferably one that can uniformly or stably dissolve or disperse each component of the ink composition of the present invention. For example, aromatic hydrocarbons such as toluene and xylene, and aliphatic carbonizations such as cyclohexane. Examples include hydrogen, esters such as ethyl acetate and butyl acetate, alcohols such as methanol and ethanol, water, and mixtures thereof. In particular, at least one of water and alcohols is preferable.
[0018]
The binder is used for fixing a reducing substance, a pH indicator, etc. on the support. Examples of such a binder include polyacrylic acid, polyvinyl alcohol, polyvinyl butyral, polyvinyl acetal, polyacetic acid. Examples include vinyl, polyurethane, and partially saponified vinyl acetate.
[0019]
In addition to the reducing substance, the pH indicator, the solvent, and the binder, the ink composition may further contain any appropriate alkalizing agent or excipient.
[0020]
Here, the alkalinizing agent may be one that promotes oxidation of reducing substances such as cysteines and cystines, or that promotes oxygen absorption, and can make the ink composition system alkaline. Any of them can be used. Examples thereof include water-soluble compounds such as alkali metal or alkaline earth metal hydroxides, carbonates, hydrogen carbonates, phosphates, borates, and the like. These may be hydrated or anhydrous. For example, sodium borate, sodium hydroxide, sodium carbonate, sodium hydrogen carbonate, lithium hydroxide, calcium phosphate, barium hydroxide, magnesium hydroxide, calcium phosphate and the like can be mentioned. Among these, sodium borate, sodium hydroxide, sodium carbonate and the like are preferable. These may be used singly or in combination of two or more.
In addition, when adding an alkalizing agent, the color tone change reaction of the pH indicator in the ink composition is promoted, a vivid color tone is expressed, and the presence or absence of oxygen may be more reliably detected.
[0021]
As the excipient, any of various known materials that can be prepared in a form that the ink composition can take can be used. For example, those useful for providing a reaction field such as zeolite, activated clay, calcium silicate, crystalline cellulose and the like. It is preferable that the excipient has a color that does not obstruct visual confirmation of the discoloration of the dye of the oxygen indicator as much as possible, for example, colorless or light color.
[0022]
In addition, the coating film formed by printing the ink composition usually exhibits the desired oxygen sensing ability or oxygen absorption ability together with the coating film itself and the moisture present in the package used. However, in cases where there is not enough moisture in the package to detect oxygen and absorb oxygen, a substance with deliquescent properties such as calcium chloride should be used to obtain this from the atmosphere. It can also be further blended into the composition.
[0023]
As a method for dissolving or dispersing the reducing substance, pH indicator, binder and the like in a solvent, all the above components may be mixed and kneaded by a general mixing and dispersing means such as a sand mill, a ball mill, a roll mill, and an attritor. . By dissolving or dispersing, the ink composition becomes an ink composition uniformly containing an aqueous solution or organic solvent solution containing a reducing substance and a pH indicator.
[0024]
As a method of applying the ink composition on the support, a printing method such as a screen printing method, an intaglio printing method, a relief printing method, a gravure printing method, a flexographic printing method and an offset printing method, a coating method such as, for example, Examples thereof include roll coating, spray coating, dip coating, and solid coating, and a printing method is preferably used.
The ink composition can be printed on a support such as a gas-impermeable packaging material to produce an oxygen detector. For example, when a packaging bag is processed by continuously printing an oxygen detector on a support, and heat-sealing and cutting, the support can be wound and supplied, so gravure printing and flexographic printing are suitable. Yes.
[0025]
The support is preferably a material that does not react with the ink composition and does not inhibit the coloration of the reagent. For example, paper, synthetic paper, non-woven fabric, or synthetic resin film can be used according to the purpose and usage.
Moreover, it is preferable that an oxygen detection part consists of an ink layer which has patterns, such as a character and a pattern.
In particular, when a character is selected as the shape of the oxygen detector, a product name, a component name, an instruction for use, etc. can be displayed. Furthermore, in order to make the oxygen detection part easy to see, the support can be appropriately colored.
[0026]
The package with an oxygen indicator function is preferably a container made of a gas permeable material containing contents such as medicines, medicines, and foods (including beverages), and is wrapped with a gas non-permeable wrapping material. It can be manufactured by providing a deoxygenated atmosphere and placing an oxygen detector in the package.
The oxygen detector can be provided on the outer surface of the gas permeable container, the space between the gas permeable container and the gas impermeable packaging material, and the inner surface of the gas impermeable packaging material. As a method of disposing an oxygen detector on the outer surface of a gas permeable container or the inner surface of a gas non-permeable packaging material, a method of adhering an oxygen detector prepared by printing an ink composition to these surfaces, or an ink composition Can be printed directly on these surfaces. Preferably, printing is performed directly on the surface of these containers or packaging materials. It is also possible to use the gas permeable container itself as a support, apply the ink composition to the outer surface of the gas permeable container, and use the gas permeable container itself as the oxygen detector. Alternatively, the gas-impermeable packaging material itself can be used as a support, the ink composition can be applied to the inner surface of the gas-impermeable packaging material, and the gas-impermeable packaging material itself can be used as the oxygen detector.
When printing the ink composition directly on the outer surface of the gas-permeable container or the inner surface of the gas-impermeable packaging material, print it after printing the ink composition on the outer surface of the gas-permeable container or the inner surface of the gas-impermeable packaging material. It is also possible to cover the surface with a gas permeable film, and when covered, there is no contact with the contents or the container, which is hygienic and can prevent wear of the indicator. Examples of the gas permeable film used here include low density polyethylene, linear low density polyethylene, polypropylene, ionomer, and ethylene-vinyl acetate copolymer.
[0027]
Contents include medicines, medicines, foods (including beverages) that are easily altered by contact with oxygen, or medicines, medicines, foods (including beverages) that may lose quality or lose their efficacy. Can be mentioned. These medicines, drugs, foods (including beverages) and the like are not particularly limited.
Examples of the drug and drug include amino acid drug solutions, carbohydrate drug solutions, vitamin-containing drug solutions, bicarbonate drug solutions, fat emulsions, and antibiotic preparations. Examples of amino acid drug solutions include amino acid infusion solutions containing essential amino acids and the like, glycyrrhizin preparations, and saccharide drug solutions include sugar infusion solutions containing, for example, reducing sugars, and vitamin-containing drug solutions include, for example, mixed vitamins. Examples of bicarbonate chemicals include, for example, artificial kidney dialysate, perfusate and replenisher, peritoneal dialysate, dental root canal enlarger, artificial spinal fluid, organ preservative, intraocular perfusate, heart Examples of fat emulsions include perfusate, myocardial protective solution, peritoneal washing solution, antidote, and vegetable oil emulsion.
Examples of foods (including beverages) include tea, coffee, cheese, ham, miso and raw meat.
[0028]
As a gas permeable container for containing or filling medicines, medicines, foods (including beverages) and the like, those conventionally used in the technical field can be used. Preferably, a gas permeable plastic container is used. For example, the thing made from polyethylene, the ethylene vinyl acetate copolymer, the product made from a polypropylene, the product made from polyethylene, or the thing which mix | blended or laminated these in the appropriate ratio etc. are mentioned. There are no particular restrictions on the shape and size of these containers. For example, a rectangular or cylindrical thing is mentioned. Moreover, although the internal volume is not specifically limited, Preferably the container of the range of about 2 mL-about 3L is used.
[0029]
“Gas impermeable” in the gas impermeable packaging material of the present invention does not necessarily mean that gas does not permeate strictly, but means that the gas impermeable is larger than that of the gas permeable container. However, this can be used as a gas-impermeable packaging material according to the present invention even when the material is the same as that of the container and the thickness thereof is large. The material of the gas-impermeable packaging material is not particularly limited, and is preferably generally used as such a packaging material, for example, polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polyvinyl alcohol. (PVA), ethylene vinyl alcohol copolymer (EVOH), polyvinylidene chloride (PVDC), nylon, etc., and those on which inorganic substances such as silicon oxide and aluminum oxide are further deposited on these surfaces, these The thing which consists of a multilayer film (laminated film) of various materials is mentioned. The shape, size, etc. of these gas-impermeable packaging materials are not particularly limited as long as the gas-permeable container can be accommodated. Preferably, the size is about 1.2 to about 3 times the volume of the gas permeable container.
[0030]
By this invention, the malfunction of the package body which consists of a gas-impermeable packaging material can be detected easily. The defect includes, for example, a change in gas atmosphere due to occurrence of pinholes, defective seals, and the like. More specifically, oxygen intrusion into the package due to the occurrence of pinholes in the package made of gas-impermeable packaging material, air leakage due to poor sealing of the package, incomplete deaeration, etc. included.
[0031]
Examples of means for making a package in which a gas permeable container is packaged with a gas impermeable packaging material into a deoxygenated atmosphere include a gas replacement method, a vacuum packaging method, and a deoxidizer method.
Examples of the gas replacement method include a method in which a mixed gas containing carbon dioxide such as nitrogen gas, carbon dioxide, or a mixed gas of carbon dioxide and nitrogen gas is enclosed in the package.
Examples of the vacuum packaging method include a method using a vacuum packaging machine. As the vacuum packaging machine, those widely used in the technical field can be used.
Examples of the oxygen scavenger method include a method using an oxygen scavenger. As the oxygen scavenger, AGELESS (Mitsubishi Gas Chemical Co., Ltd.) or the like can be used.
Although the package of the present invention is obvious from the above, it is produced by a method known per se. Preferably, medicines or foods (including beverages) that are easily altered by oxygen are contained in a gas permeable container, and further packaged in a gas impermeable packaging material so that the gas impermeable packaging body has a deoxygenated atmosphere. It is manufactured by providing an oxygen detector by printing an ink composition on a support.
Note that when cysteines or cystines are used as the reducing substances, they also serve as oxygen scavengers, so that it is not necessary to use oxygen scavengers.
[0032]
【Example】
EXAMPLES Examples and test examples of the present invention will be described below. However, the following examples and test examples are only preferred embodiments of the present invention, and do not limit the technical scope of the present invention.
[0033]
Example 1
L-cysteine hydrochloride (Wako Pure Chemical Industries) 6.0g
Methylene blue (Wako Pure Chemical Industries) 4.0g
Isopropyl alcohol (Osaka Printing Ink) 33.0g
100.0 g of water
5 parts by weight of yellow ink (WS Yellow 2RN-1T manufactured by Toyo Ink Co., Ltd.) containing 1 part by weight of a solution obtained by mixing the above components with respect to 50 parts by weight of polyvinyl alcohol (JIP41C) and further containing an ultraviolet absorber Part was added. An ink composition using a water-soluble binder resin was obtained by kneading for 1 hour in a sand mill.
Oxygen permeability 1ml / m ² The ink composition for oxygen detection was printed on the PVA film of oxygen impermeable packaging material of / 24 hr / atm or less by a gravure printing method, and an LLDPE film was laminated on the printed surface to form a sealant layer. Moreover, a PET film was laminated on the surface layer surface, and a gas-impermeable packaging material provided with an oxygen detector by printing was obtained.
[0034]
As a content, a polyethylene container containing 500 mL of an amino acid infusion solution having the composition shown below is packaged with the packaging material prepared above, with the surface having the oxygen detection portion inside, and a space portion ( After replacing nitrogen gas with a volume of about 100 mL), oxygen absorber Ageless (ZH-100P) was added and the packaging material was sealed to obtain a package with an oxygen indicator function of the present invention.
Amino acid infusion
L-leucine 7.0 g, L-isoleucine 4.0 g, L-valine 4.0 g, L-lysine acetate 7.4 g, L-threonine 2.85 g, L-tryptophan 1.0 g, L-methionine 1.95 g, L-phenylalanine 3.5 g, L-cysteine 0.5 g, L-tyrosine 0.25 g, L-arginine 5.25 g, L-histidine 2.5 g, L-alanine 4.0 g, L-proline 2.5 g, L -Serine 1.5g, aminoacetic acid 2.95g, L-aspartic acid 0.5g, L-glutamic acid 0.5g and glacial acetic acid 1.45g were dissolved in distilled water to obtain a 500 mL solution.
[0035]
24 hours after sealing, the space became anoxic, and this was confirmed by the fact that the blue oxygen detector immediately turned yellow after 24 hours of sealing.
[0036]
Comparative Example 1
A gas impermeable packaging material was obtained by laminating an LDPE film on a PVA film, which is a gas impermeable packaging material, to form a sealant layer, and laminating a PET film on the surface layer. As an oxygen indicator, Mitsubishi Gas Chemical's Ageless Eye Type: Paper Eye P Eye-M was used.
The polyethylene container containing 500 mL of the above amino acid infusion solution is packed with the packaging material prepared above, and the oxygen scavenger AGELESS (ZH-100P) is put together with the AGELESS eye, and the space between the container and the wrapping material (volume: about 100 mL) After substituting with nitrogen gas, it was sealed in an oxygen-free state and stored under each condition. The space became oxygen-free 24 hours after sealing, which was confirmed by the fact that the ageless eye, which was purple immediately after sealing, turned pink after 24 hours of sealing.
[0037]
Example 2
An ink composition was prepared in exactly the same manner as in Example 1. In the same manner as in Example 1, this was coated on an alumina-deposited PET film by screen printing, dried at 70 ° C. for 1 hour, an LDPE film was laminated on the printed surface to form a sealant layer, and a PET film was laminated on the surface layer surface. Thus, a gas-impermeable packaging material provided with an oxygen detector was obtained.
As a content, a polyethylene container containing 20 mL of the glycyrrhizin preparation containing cysteine shown below is packaged with the packaging material in which the oxygen detector prepared above is formed with the surface having the oxygen detector inside, and then removed. It was put together with oxygen agent Ageless (ZH-10P), the space between the container and the packaging material (volume: about 30 mL) was replaced with nitrogen gas, and then the packaging material was sealed to obtain a package with an oxygen indicator function of the present invention.
Glycyrrhizic acid preparation
Glycyrrhizin 40 mg, aminoacetic acid 400 mg and L-cysteine 20 mg were dissolved in distilled water to obtain a 20 mL solution.
[0038]
The space became oxygen-free 24 hours after sealing, which was confirmed by the fact that the blue oxygen detection member turned yellow after sealing 24 hours after sealing.
[0039]
Comparative Example 2
Similarly to Example 2, a polyethylene container containing 20 mL of a glycyrrhizin preparation was packaged with a gas-impermeable packaging material made of an alumina-deposited PET film on which an oxygen detection member was not printed. −10P), the space between the container and the packaging material (volume: about 30 mL) was replaced with nitrogen, and the packaging material was sealed to obtain Comparative Example 2.
24 hours after sealing, the space became anoxic, which was confirmed by the fact that the ageless eye, which was purple immediately after sealing, turned pink after 24 hours of sealing.
[0040]
Test example 1
A pinhole (diameter: about 500 μm, minor diameter: about 50 μm) is opened in the packaging material of the packaging body produced in Examples 1 and 2 and Comparative Examples 1 and 2 with an injection needle (27G, Terumo, Neolas), and the packaging body The color change of the oxygen detection part in was visually observed from the outside. The results are shown in the table below. The color change time represents the time until the color change reaction after the pinhole is completed.
[Table 1]

[0041]
Test example 2
Ink compositions were prepared and investigated for stability to light and heat. In the same manner as in Test Example 1, a polyethylene container containing 500 mL of an amino acid infusion solution was packaged with the packaging material of the present invention package prepared in Examples 1 and 2, and oxygen scavenger AGELESS (ZH-100P) was added, and nitrogen was added. Sealed after replacement and stored under various conditions as anoxic conditions.
As a comparative example, a polyethylene container containing 500 mL of paper eye and amino acid infusion solution is packaged with the packaging material prepared in Comparative Examples 1 and 2, put oxygen scavenger Ageless (ZH-100P), sealed after nitrogen substitution, It was stored under each condition as anoxic state.
[0042]
(1) Light stability test
Pasted and stored on the window glass irradiated with sunlight, we investigated the change in color. The results are shown in the table below.
[Table 2]

[0043]
In Comparative Examples 1 and 2, the color tone became unstable after 3 days, whereas in Examples 1 and 2, an anaerobic yellow color was exhibited even after 5 days. When the package packaged with the gas-impermeable packaging material after 14 days was opened, the color returned to blue in Examples 1 and 2, but the color did not change in Comparative Examples 1 and 2.
[0044]
(2) Stability test
The change in color tone was investigated over time at 40 ° C. and oxygen-free storage. The results are shown in the table below.
[Table 3]

[0045]
In Comparative Examples 1 and 2, the color tone exhibited during anoxia after 2 months was poor, whereas in Examples 1 and 2, the yellow color of anoxic color was exhibited even after 3 months. When the package packaged with the gas-impermeable packaging material after 3 months was opened, the color returned to blue in Examples 1 and 2, but no change in color in Comparative Examples 1 and 2.
[0046]
【The invention's effect】
According to the present invention, discoloration of the oxygen detector can be easily confirmed from the outside, and further, a package with an oxygen indicator function having excellent light stability and discoloration speed can be obtained.

Claims (11)

A gas permeable container containing a drug or food that is easily altered by oxygen is packed with a gas impermeable packaging material, and the inside of the package is deoxygenated by gas replacement, vacuum, or an oxygen scavenger. A package is provided with an oxygen detection unit for detecting a gas atmosphere change of the package due to a defect in the packaging material by color change, and the oxygen detection unit is provided with cysteines and thiazine dyes and / or indigo A package with an oxygen indicator function, which is a coating film formed by an ink composition containing an aqueous solution containing a pigment or an organic solvent solution .   The drug or food that is easily altered by oxygen is one or more selected from the group consisting of amino acid drug solutions, carbohydrate drug solutions, vitamin-containing drug solutions, bicarbonate drug solutions, fat emulsions, and antibiotic preparations. The package with an oxygen indicator function according to claim 1.   The package with an oxygen indicator function according to claim 1 or 2, wherein the medicine or food that is easily altered by oxygen is a glycyrrhizin preparation. The package with an oxygen indicator function according to any one of claims 1 to 3 , wherein the concentration of cysteines is 100 to 100,000 ppm. Cysteine is L-cysteine, L-cysteine hydrochloride, DL-cysteine, DL-cysteine hydrochloride, D-cysteine, D-cysteine hydrochloride, L-ethylcysteine hydrochloride, L-methylcysteine hydrochloride, acetylcysteine, S- The package with an oxygen indicator function according to any one of claims 1 to 4, wherein the package is one or two or more selected from the group consisting of carboxymethyl-L-cysteine . The package with an oxygen indicator function according to any one of claims 1 to 5, wherein the concentration of the thiazine dye and / or the indigo dye is 100 to 100,000 ppm. Thiazine dyes and / or indigo dyes are composed of Ultra Violet, Azure C, Azure B, Methylene Blue, Methionine Blue, New Methylene Blue, Methylene Green, Rous Violet, Neomethylene Blue, Brilliant Alizarin Blue, Indigo, Indigo Carmine, Bromine Indigo R It is 1 type, or 2 or more types selected from a group, The package with an oxygen indicator function in any one of Claims 1-6 characterized by the above-mentioned. The package with an oxygen indicator function according to any one of claims 1 to 7 , wherein printing is displayed on an outer surface of a gas permeable container or an inner surface of a gas impermeable packaging material. The package with an oxygen indicator function according to any one of claims 1 to 8 , wherein the oxygen detector is a pinhole detector. A pharmaceutical or food that is easily altered by oxygen stored in a gas-permeable container of the package with an oxygen indicator function according to any one of claims 1 to 9 . A medicine or food easily altered by oxygen, wherein the medicine or food easily altered by oxygen is stored and stored in the gas-permeable container of the package with an oxygen indicator function according to any one of claims 1 to 9. How to save.