Packaging materials, seal coating agents, and PTP packaging

Abstract

The present invention provides PTP packaging materials, seal coating agents, and PTP packaging bodies that suppress the generation of nitrosamines such as NDMA and NDEA. [Solution] The packaging material 10 consists of a base material 11 made of aluminum foil and a heat-sealable seal coat layer 12 applied to one surface of the base material 11. The seal coat layer 12 contains 20-40 wt% zeolite and 60-80 wt% heat-sealable resin, and the pH value of the slurry when the zeolite is dispersed in water at a concentration of 1 wt% is 7 or less. The PTP packaging body 20 consists of a container 21, contents 22 that generate amines contained in the container 21, and the aforementioned packaging material 10 that seals the container 21.

Description

Technical Field

[0001] The present invention relates to a packaging material, a seal coat agent used therefor, and a PTP package using the packaging material.

Background Art

[0002] A PTP package widely used for packaging pharmaceuticals and the like is composed of a container for storing contents, the contents stored in the container, and a lid material heat-sealed to the container (see, for example, Patent Document 1). The container is constituted by a processed molded body of a plastic sheet having a pocket portion formed therein (so-called PTP sheet). The lid material is configured by providing a printing layer on one or both sides of, for example, a metal foil, particularly an aluminum foil, further providing a heat-resistant coating layer on each of the upper surfaces thereof, and providing a seal coat layer on the surface joined to the container.

[0003] As the plastic sheet, vinyl chloride resin sheets and polypropylene sheets having a certain degree of gas barrier property have been used for a long time. And the lid material mainly composed of aluminum foil has a gas barrier property. Therefore, PTP packaging has relatively high airtightness and can protect the contents such as pharmaceuticals from the outside air. On the other hand, gases generated from pharmaceuticals and the like tend to remain, and harmful gases are a problem.

[0004] For example, there has been a report that a carcinogenic substance, "N-nitrosodimethylamine (NDMA)", has been detected from pharmaceuticals used in PTP packages, particularly sartan-based pharmaceuticals such as valsartan, and the active ingredient and formulations of ranitidine hydrochloride, which is a histamine H2 receptor antagonist. Since such NDMA or nitrosoamines such as N-nitrosodiethylamine (NDEA) similar thereto are carcinogenic, it is necessary to remove the PTP package before it is purchased by consumers.

[0005] Patent Document 2 proposes the use of porous microparticles as an adsorbent for adsorbing harmful substances such as nitrosamines. Claim 13 of the claims in this document and paragraph

[0029] of the specification describe a moisture adsorbent containing an iron-containing porous organic-inorganic hybrid obtained by a specific manufacturing method and having a predetermined pore volume. However, this adsorbent is said to readily adsorb and desorb even at temperatures below 100°C, and therefore cannot be used for the purpose of removing nitrosamines from PTP packaging stored at room temperature.

[0006] Patent Document 3 discloses an aluminum laminate (lid material) for PTP packaging, comprising a base material made of aluminum foil and a sealing layer provided on the base material, wherein the sealing layer contains an inorganic porous material and a heat-sealable resin. This laminate can adsorb odor components generated from the contents by the inorganic porous material without impairing the heat-seal function to the container. Examples of inorganic porous materials include zeolites with a particle size of 0.1 to 10 μm, and examples of heat-sealable resins include vinyl chloride / vinyl acetate copolymer resins.

[0007] Furthermore, the [Examples] section of this document discloses that a laminate and the odor component diacetyl were placed in a sampling bag, and a reduction of more than 90% in diacetyl was detected by a gas detection tube. However, while the zeolite in this laminate has the ability to adsorb only diacetyl, it has not been modified in a way that would allow it to adsorb amines, so it does not adsorb amines. [Prior art documents] [Patent Documents]

[0008] [Patent Document 1] Japanese Patent Publication No. 2023-166720 [Patent Document 2] Patent No. 5551119 [Patent Document 3] Japanese Patent Publication No. 2022-92786 [Overview of the project] [Problems that the invention aims to solve]

[0009] The present invention aims to provide a packaging material that suppresses the formation of nitrosamines such as NDMA and NDEA, a seal coating agent for use in the packaging material, and a PTP packaging. [Means for solving the problem]

[0010] The packaging material 10 of the present invention consists of a base material 11 mainly made of aluminum foil and a heat-sealable seal coat layer 12 applied to one surface of the base material 11, wherein the seal coat layer 12 contains 20-40 wt% zeolite and 60-80 wt% heat-sealable resin, and the zeolite is characterized in that the pH value of the slurry when dispersed in water at a concentration of 1 wt% is 7 or less.

[0011] In such packaging material 10, the zeolite is preferably in the form of a powder or granules with an average particle size of 90 nm to 5 μm. Furthermore, it is preferable that the average pore diameter of the zeolite is 0.5 to 0.8 nm.

[0012] The seal coating agent of the present invention is a seal coating agent that, when applied to and dried on one surface of a substrate 11 mainly composed of aluminum foil, forms a seal coating layer 12 of a packaging material 10. The agent contains 20-40 wt% zeolite and 60-80 wt% heat-sealable resin as solid components excluding the solvent, and is characterized in that the pH value of the slurry when the zeolite is dispersed in water at a concentration of 1 wt% is 7 or less.

[0013] The PTP packaging 20 of the present invention comprises a container 21 for PTP packaging, contents 22 that generate amines contained in the container 21, and a packaging material (lid) 10 that seals the container 21, wherein the packaging material 10 is made of any of the aforementioned packaging materials. [Effects of the Invention]

[0014] The seal coat layer of the packaging material of the present invention contains 20-40 wt% zeolite, and since the pH value of the slurry when the zeolite is dispersed at 1 wt% in water is 7 or less, alkaline or neutral amines that are the source of nitrosamine formation can be adsorbed and retained within the pores of the zeolite. Therefore, even if nitrite is present in the surroundings, the nitrosation reaction can be suppressed and the formation of carcinogenic nitrosamines can be inhibited.

[0015] Zeolites can be used to adsorb both acidic and alkaline substances, but among amines, diethylamine is alkaline and DMF is neutral. In this invention, a zeolite is used in which the pH value of the slurry when dispersed at 1 wt% in water is 7 or less, so that the target alkaline or neutral amine gases can be efficiently adsorbed.

[0016] Generally, nitrosamines are produced by the nitrosation reaction of amines (secondary, tertiary, and quaternary amines) with nitrite (sodium nitrite, etc., under acidic conditions). The NDMA production pathway in sartan drugs is thought to be through the nitrosation reaction between N,N-dimethylformamide (DMF) contained in the drug and nitrocellulose resin contained in the printing ink of PTP aluminum foil or nitrogen dioxide in the atmosphere.

[0017] The packaging material of the present invention quickly adsorbs amines (DMF, dimethylamine, diethylamine), which are substances that lead to the formation of nitrosamines, and retains them within its pores, thereby efficiently suppressing the formation of carcinogenic substances such as NDMA and NDEA.

[0018] When the zeolite is a powder or granule with an average particle diameter of 90 nm to 5 μm, it is easy to incorporate it into the seal coat layer. When the average pore diameter of the zeolite is 0.5 to 0.8 nm, it exhibits a porous state effective for adsorption and retention with respect to the size of the amines that are the adsorption targets, and the efficiency of adsorption and retention is high. For example, N,N-dimethylformamide (DMF) and dimethylamine enter the zeolite with a pore diameter of 0.55 nm (ZMS-5 (Zeaol (registered trademark) HZSM-5 manufactured by Nakamura Superhard Co., Ltd.)), and diethylamine enters the Y-type zeolite with a pore diameter of 0.74 nm (Zeaol (registered trademark) high silica Y manufactured by Nakamura Superhard Co., Ltd.). Therefore, it is preferable that the average pore diameter of the zeolite is 0.5 to 0.8 nm.

[0019] The seal coat agent of the present invention can be used to produce the aforementioned packaging material by applying and drying it on an aluminum base material.

[0020] The PTP package of the present invention adsorbs and retains the amines generated by the pharmaceutical product. Therefore, even if nitrous acid is present in the surroundings, the nitrosation reaction can be suppressed, and the generation of carcinogenic nitrosamines can be suppressed.

Brief Description of the Drawings

[0021] [Figure 1] It is a cross-sectional view schematically showing an embodiment of the packaging material of the present invention. [Figure 2] It is a cross-sectional view schematically showing an embodiment of the PTP package of the present invention.

Modes for Carrying Out the Invention

[0022] The packaging material 10 shown in Figure 1 consists of a base material 11 mainly made of aluminum foil and a heat-sealable seal coat layer 12 coated on one surface thereof. This packaging material 10 is used as a lid material to seal the container 21 of a PTP package 20 (see Figure 2). The base material 11 is made of aluminum foil with a thickness that can be torn by pressing with a finger, for example, 10 to 30 μm thick. Typically, the base material 11 is provided with a printing layer on the front and back surfaces of the aluminum foil for printing the name of the contents, and a heat-resistant layer to protect the printing layer from the heat during heat sealing.

[0023] The seal coat layer 12 is obtained by applying a liquid seal coat agent containing 20-40 wt% zeolite (adsorbent), 60-80 wt% heat-sealable resin, and a solvent to the substrate 11 and drying the solvent. The coating film formed as the seal coat layer 12 has a density of 3-10 g / m². 2 The proportion of zeolite in the seal coat film used therein is 20-40 wt% (0.6-4 g / m²). 2 This range allows for effective adsorption of amine gases while maintaining the performance and functionality of the heat sealant.

[0024] If the proportion of adsorbent in the seal coat film is less than 20%, the adsorption effect of amine gases will decrease, and if it exceeds 40%, the performance as a heat sealant (heat sealability, seal strength, etc.) will decrease.

[0025] Both natural and synthetic zeolites can be used as zeolites. Zeolites can be modified to be acidic or alkaline, but for amines, DMF is neutral, while dimethylamine and diethylamine are alkaline. Therefore, in this invention, the zeolite used to adsorb the target amine gases is neutral or acidic, such that the pH of the slurry when dispersed at 1 wt% in water is 7 or less. Furthermore, since the pH of dimethylamine and diethylamine is 13-14, it is preferable that the pH of the zeolite be 7 or less. A pH value lower than 7 is acidic, and a pH value of 7 is neutral. And since the pH of N,N-dimethylformamide (DMF) is 7, it is preferable that the pH of the zeolite be around 4-5. To modify the zeolite to be acidic, for example, fine particles of zeolite can be immersed in ammonium nitrate or ammonium sulfate and ion exchange (Na+ → NH4 + This can be done by first preparing the zeolite to a neutral pH, and then protonating it by firing it at 350°C or higher. Alternatively, acid-modified zeolites, such as Zeaol® High Silica Y manufactured and sold by Nakamura Choko Co., Ltd., can also be obtained by purchasing them.

[0026] Furthermore, the zeolite may have any external shape, such as spherical, rod-shaped, or elliptical, and may be in any form, such as powder, lump, or granules. However, from the viewpoint of ease of coating as a seal coat layer, ease of forming a coating film, and uniform mixing characteristics with heat-sealable resin, powder or granules are preferred.

[0027] The size of the zeolite can be selected as appropriate, but in order to more effectively adsorb the target adsorbent material, and to form a transparent coating on the design printed on the AL foil, providing transparency that does not impair the visibility of the design, a zeolite with an average particle size of 90 nm to 5 μm is particularly preferred in this invention.

[0028] When the average particle size is less than 90 nm, aggregation of inorganic porous materials tends to occur, suppressing uniform dispersion in the seal coat layer. Furthermore, when the average particle size exceeds 5 μm, it inhibits the formation of the seal coat layer, preventing sufficient heat sealing performance, which tends to impair the protective sealing of the contents and reduces the visibility of designs printed on the aluminum foil. Here, the average particle size is the value measured by dynamic light scattering.

[0029] Furthermore, reducing the particle size naturally increases the number of zeolites in the coating film, thus increasing the number of pores in the coating film. The more pores there are, the faster the adsorption speed. The diameter of the pores should be larger than the target amine gas. However, if they are too large, the amine gas that has entered will escape again. Therefore, it is preferable that the pores of the zeolite be porous, with a size that is effective for the size of the amine to be adsorbed.

[0030] For example, if the average diameter of the pores is less than 0.5 nm, the efficiency of adsorption of amine gases decreases. On the other hand, regarding the release of amine gases once adsorbed, it is difficult to give precise figures because it is greatly influenced by external environmental factors such as temperature, and there is also the compatibility between the zeolite and the adsorbed gas. However, for example, in the case of macropores with an average diameter greater than 50 nm, the adsorbed amine gases cannot be sufficiently retained and are easily released.

[0031] The heat-sealable synthetic resin used in the seal coating agent depends on the material of the container (molded material, reference numeral 21 in Figure 2) to be heat-sealed, but suitable resins can be selected individually or in combination from vinyl chloride-vinyl acetate copolymer resins, polyolefin resins, acrylic resins, polyester resins, etc. If the container 21 is made of vinyl chloride resin, vinyl chloride-vinyl acetate copolymer resin is preferred.

[0032] The base material 11, which is aluminum foil, and the printing ink used to apply the design on it, can be the same as those that have been used conventionally. Furthermore, since the packaging material for PTP packaging of the present invention is used in particular for pharmaceutical PTP packaging, the contents are not food, and the seal coating agent that comes into direct contact with the contents is not subject to the Food Sanitation Act. However, since pharmaceuticals packaged in PTP are oral medications, they often comply with the Food Sanitation Act. Therefore, there are restrictions on the amount of zeolite that can be used under the Food Sanitation Act, and it is preferable that the amount used be 30 wt% or less in the heat seal agent, and even in that case, the desired performance can be obtained with this amount.

[0033] The PTP packaging 20 in Figure 2 consists of a container 21, contents 22 such as pharmaceuticals contained in pockets 21a of the container 21, and the aforementioned packaging material 10 heat-sealed to the flange 21b of the container 21. The container 21 can be manufactured by molding multiple pockets 21a into a conventionally used thermoplastic resin sheet, such as a polyvinyl chloride sheet or a polypropylene sheet. It is preferable that the container 21 be transparent so that the contents and the text printed on the packaging material 10 are visible. The container 21 can also contain the same zeolite as described above.

[0034] The contents 22 contained in container 21 generate amines. Examples of such contents 22 include sartan drugs such as valsartan, and the active pharmaceutical ingredient and preparation of ranitidine hydrochloride, a histamine H2 receptor antagonist.

[0035] To obtain the PTP packaging 20, the contents 22 are placed in the pocket 21a of the container 21, and the packaging material 10 is pressed against the flange 21b of the container 21 and heated to heat-seal it. This seals the pocket 21a, protecting the contents 22, such as pharmaceuticals, from the outside air. Furthermore, amines released from the contents 22 are adsorbed and retained by the zeolite in the seal coat layer 12 of the packaging material 10. Therefore, even if nitrogen oxides or nitrites are present in the surroundings, or even if nitrogen (air) is present in the pocket 21a, nitrosamines will not be generated. Consequently, the possibility of cancer in the user is suppressed. [Examples]

[0036] [Example 1] A liquid seal coating agent containing 20 wt% zeolite (adsorbent), 80 wt% PVC / vinyl acetate copolymer resin (heat-sealable resin), and a solvent (MEK, toluene, etc.) is applied to one side of a substrate made of 20 μm thick aluminum foil using a bar coater, and the solvent is dried to obtain a basis weight of 4.0 g / m². 2 (Zeolite content 0.8g / m 2 A packaging material of Example 1 having a seal coat layer was manufactured. The zeolite used was Zeaol® High Silica Y, product number from Nakamura Choko Co., Ltd. The pH value of the zeolite was 4.8, the particle size distribution D50 was 578 nm, D90 was 1120 nm, and the average pore diameter was 0.8 nm. Note that the values ​​in parentheses in Table 1 represent the seal coat layer of 4.0 g / m². 2 This is the amount of zeolite inside.

[0037] [Examples 2 and 3] Packaging materials for Example 2 and Example 3 were manufactured in the same manner as in Example 1, except that the zeolite content was 30 wt% and 40 wt%, respectively, and the heat-sealable resin content was 70 wt% and 60 wt%, respectively.

[0038] [Comparative Examples 1-3] Comparative Examples 1, 2, and 3 were manufactured in the same manner as in Example 1, except that the zeolite content was set to 0 wt%, 15 wt%, and 45 wt%, respectively, and the heat-sealable resin content was set to 100 wt%, 85 wt%, and 55 wt%, respectively.

[0039] [Experimental Example 1] N,N-dimethylformamide (DMF) was used as the adsorbed sample gas, and the rate of DMF reduction and heat seal strength were measured using the following method.

[0040] (Decrease rate measurement method) Four samples, each obtained by cutting the packaging material from Examples 1-3 and Comparative Examples 1-3 to 100mm x 100mm, were placed in a 5L sampling bag. 3L of clean air was then injected, and sample gas was added to achieve an initial concentration (approximately 90ppm). After 48 hours, the gas concentration was measured using a gas detection tube. Since accurately injecting 90ppm was difficult, the actual concentration value was measured. The sample gas concentration in the sample bag on the first day was set as 100%, and the decrease in sample gas after 48 hours was observed. The sample gas decrease rate in the blank test was considered as a factor.

[0041] • Gas detection tube: N,N-dimethylformamide No. 183 (Gastec) • Sampling bag: Smart Bag PA 5L AF-5

[0042] (Method for measuring seal strength) Material of adherend (container): PVC 200μm Sealing conditions: 150°C × 0.29 MPa × 1 second The packaging material was pressure-welded to the adherend under the above sealing conditions, and the force required to peel back 15 mm from the edge of the 20 mm wide packaging material, which was folded back 180 degrees, was measured as the seal strength. • Measuring device: AGS-X manufactured by Shimadzu Corporation

[0043] [Table 1]

[0044] [Test Results] In Comparative Example 1, which contained no zeolite, and Comparative Example 2, which contained 15 wt% zeolite, the seal strength was high at 17.5 and 17.2 N / 15 mm, respectively. However, the sample gas, DMF, either did not decrease or decreased only slightly at 63% after 48 hours. On the other hand, in Comparative Example 3, which contained 45 wt% zeolite, the DMF decrease rate was high, but the seal strength was low at 9.6 N / 15 mm, making it impractical. In contrast, Examples 1, 2, and 3, with zeolite contents of 20 wt%, 30 wt%, and 40 wt%, showed sufficient DMF decrease rates of 83%, 85%, and 86% after 48 hours, respectively, and also demonstrated high seal strengths of 17.0 N / 15 mm, 16.9 N / 15 mm, and 15.8 N / 15 mm, which are suitable for practical use.

[0045] [Experimental Example 2] Diethylamine was used as the sample gas, and the rate of decrease in the sample gas concentration and the heat seal strength were measured in the same manner as in Experimental Example 1, except that the sample gas was injected into the sample bag to reach the initial concentration (approximately 110 ppm).

[0046] [Table 2]

[0047] • Gas detector tubes: Amines No. 180 (measurement range: 5.5~110 ppm) (Gastec), Amines 180L (measurement range: 0.45~9 ppm) (Gastec) • Sampling bag: Smart Bag PA 5L AF-5

[0048] [Test Results] In Comparative Example 1, which did not contain zeolite, and Comparative Example 2, which contained 15 wt% zeolite, the seal strength was high at 17.5 N / 15 mm and 17.2 N / 15 mm, respectively. However, the sample gas, diethylamine, either did not decrease or decreased only slightly at 74% after 48 hours. In contrast, in Examples 1-3, which contained zeolite, the diethylamine decreased significantly at 95%, 97%, and 95%, respectively, and the seal strength was also within a practical range of 17.0-15.8 N / 15 mm. On the other hand, in Comparative Example 3, which contained 45 wt% zeolite, the diethylamine decreased sufficiently at 96% after 48 hours, but the seal strength was a low and impractical 9.6 N / 15 mm.

[0049] For reference, Table 3 shows the target amine gases, their pH values, and molecular weights. [Table 3]

[0050] Table 4 shows the pH values ​​of the zeolite used in the experiment (pH values ​​of the slurry dispersed at 1 wt% in water). [Table 4]

[0051] In the above embodiment, the lid material for PTP packaging was described as an application of the packaging material, but it can also be used as a sheet for blister packaging or bag packaging. Comparing Experimental Example 1 and Experimental Example 2, when the pH of the zeolite is the same at 4.8, the amine gases show a higher adsorption rate at the higher pH (Experimental Example 2). From this, it can be inferred that the adsorption rate will be higher when the pH value of the zeolite (pH value of the slurry dispersed at 1 wt% in water) is low (acidic side) and the difference with the pH value of the amine is large, and the adsorption rate will be lower when the pH value of the zeolite is high (alkaline side). Experiments were not conducted on dimethylamine gas, but since its pH value is higher than that of diethylamine, it is inferred that the reduction rate will be higher than that of diethylamine. [Explanation of symbols]

[0052] 10 Packaging materials 11 Base material 12 Seal Coat Layer 20 PTP packaging 21 Container 21a Pocket 21b Flange 22. Contents (Pharmaceuticals)

Claims

1. It consists of a base material mainly composed of aluminum foil and a heat-sealable seal coat layer applied to one surface of the base material. The seal coat layer contains 20-40 wt% zeolite and 60-80 wt% heat-sealable resin. The zeolite, when dispersed in water at a concentration of 1 wt%, has a pH value of 7 or less when the slurry is dispersed. packaging material.

2. The packaging material according to claim 1, wherein the zeolite is a powder or granules with an average particle size of 90 nm to 5 μm.

3. The packaging material according to claim 2, wherein the average diameter of the pores of the zeolite is 0.5 to 0.8 nm.

4. A seal coat agent that, when applied to and dried on one surface of a substrate made of aluminum foil, becomes a seal coat layer of packaging material, The solid content, excluding the solvent, consists of 20-40 wt% zeolite and 60-80 wt% heat-sealable resin. The zeolite is dispersed in water at a concentration of 1 wt%, and the resulting slurry has a pH value of 7 or less. Seal coating agent.

5. It consists of a container for PTP packaging, a pharmaceutical product that generates amines contained in the container, and a lid that seals the container. The lid is made of the packaging material described in any one of claims 1 to 3. PTP packaging.

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