JP2016123558A - Resin sheet for packaging medicament - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a resin sheet for packaging medicament in which stability, such as heat stability, equivalent to those of conventional one is maintained, and bleed out amount is small.SOLUTION: There is provided a resin sheet for packaging medicament meeting the following requirements (1) and (2): requirement (1): when the medicament packaging resin sheet (thickness of 250 μm) is heated/pressurized at temperature of 230°C and at pressure of 100 kgf, YI value (yellow index) measured with a spectrophotometer is 20 or less; and requirement (2): when the medicament packaging resin sheet is used, amount of residue on evaporation by an evaporation residue text (diffusion solution: heptane, 20% ethanol, water or 4% acetic acid) measured based on standard criteria for food, additive etc. (the Notice of the Ministry of Health and Welfare No. 370, Showa 34), 3D-2, synthetic resin tool and container packaging (class: used temperature: 100°C or less) is 20 μg/ml or less, in every case in which any diffusion solution is used.SELECTED DRAWING: None

Description

  The present invention relates to a resin sheet for packaging pharmaceuticals.

A resin sheet for packaging pharmaceuticals is required to have a small amount of bleed out from the sheet for the purpose of packaging pharmaceuticals.
This is because the efficacy or the like of the drug changes depending on the bleed-out component, and further, depending on the bleed-out component, the component may be toxic to the human body.

  Therefore, from the viewpoint of bleeding out, it is preferable not to add a third component other than the resin to the pharmaceutical packaging resin sheet, but conventionally, the pharmaceutical packaging resin sheet has various types depending on the purpose. Additives are blended. In particular, the use of a stabilizer is essential for the resin sheet in order to increase its stability.

For example, a polyvinyl chloride (PVC) sheet, which is often used as a resin sheet for pharmaceutical packaging, tends to discolor due to heat during molding and the like, so that the sheet has conventionally prevented this discoloration. Therefore, a stabilizer is used, and an organotin stabilizer is known as the stabilizer (for example, Patent Document 1).
Most of the PVC sheets for pharmaceutical packaging used in the current market are sheets containing a tin-based stabilizer such as dioctyltin.

Japanese Patent Laid-Open No. 06-270930

  However, conventional resin sheets for packaging packaging containing additives such as stabilizers tend to bleed out components that form the sheet.

  This invention is made | formed in view of the said problem, and makes it a subject to provide the resin sheet for pharmaceutical packaging with few bleed-out amounts, maintaining stability, such as the thermal stability comparable as the past. .

As a result of intensive studies to solve the above problems, the present inventors have found that the following problems can be solved by the following resin sheet for packaging pharmaceuticals, and have completed the present invention.
A configuration example of the present invention is as follows.

[1] A resin sheet for pharmaceutical packaging that satisfies the following requirements (1) and (2).
Requirement (1): YI value (yellow index) measured with a spectrocolorimeter when the resin sheet for pharmaceutical packaging (thickness: 250 μm) is heated and pressurized at a temperature of 230 ° C. and a pressure of 100 kgf is 20 or less. Requirement (2): Using the above-mentioned resin sheet for packaging pharmaceuticals, 3D-2 of standard standards for foods, additives, etc. (Ministry of Health and Welfare Notification No. 370 of 1959), synthetic resin appliances or containers and packaging (Category: Operating temperature, 100 ° C or less) Measured based on evaporation residue test (leaching solution: heptane, 20% ethanol, water or 4% acetic acid) 20 μg / ml or less

  [2] The resin sheet for medical packaging according to [1], wherein the resin includes a vinyl chloride resin.

  [3] The resin sheet for pharmaceutical packaging according to [2], comprising the compound (I) represented by the following formula (I) or a tautomer thereof.

（式（Ｉ）中、Ｒ¹およびＲ³はそれぞれ独立に、炭素数６〜１８のアリール基、炭素数１〜１８のアルキル基、炭素数７〜１８のアラルキル基、アルキル基の少なくとも１部がハロゲン原子または酸素原子で置換された基（但し、該基の炭素数は１〜１８である。）、ヒドロキシ基、または、アリール基の少なくとも１部がアルコキシ基で置換された基（但し、該基の炭素数は７〜１８である。）であり、Ｒ²は、単結合、炭素数１〜１８のアルキレン基または炭素数７〜１８のアラルキレン基であり、Ｒ¹〜Ｒ³は互いに結合していてもよく、Ｒ²において２量体を形成してもよい。）

(In the formula (I), R ¹ and R ³ are each independently at least part of an aryl group having 6 to 18 carbon atoms, an alkyl group having 1 to 18 carbon atoms, an aralkyl group having 7 to 18 carbon atoms, and an alkyl group. Is a group substituted with a halogen atom or an oxygen atom (provided that the group has 1 to 18 carbon atoms), a hydroxy group, or a group wherein at least part of the aryl group is substituted with an alkoxy group (provided that The group has 7 to 18 carbon atoms.), R ² is a single bond, an alkylene group having 1 to 18 carbon atoms or an aralkylene group having 7 to 18 carbon atoms, and R ^{1 to} R ³ are It may be bonded, and a dimer may be formed in R ^2. )

  [4] The resin sheet for packaging pharmaceuticals according to [3], wherein the content of the compound (I) or a tautomer thereof is 0.01 to 2.0 parts by mass with respect to 100 parts by mass of the vinyl chloride resin.

  [5] The resin sheet for packaging pharmaceuticals according to any one of [1] to [4], which is a sheet for blister packs for packaging pharmaceuticals.

  ADVANTAGE OF THE INVENTION According to this invention, the resin sheet for pharmaceutical packaging with little bleed-out amount can be provided, maintaining stability, such as thermal stability comparable as the past. Therefore, according to the present invention, it is possible to provide a resin sheet for packaging pharmaceuticals, which is particularly excellent in safety and hardly changes the efficacy or the like of pharmaceuticals over a long period of time.

FIG. 1 is a diagram showing a total light transmission curve of resin sheets obtained in Example 1 and Comparative Example 1. FIG.

≪Resin sheet for pharmaceutical packaging≫
The resin sheet for packaging pharmaceuticals of the present invention (hereinafter also simply referred to as “resin sheet”) satisfies the following requirements (1) and (2).
Requirement (1): The YI value (yellow index) measured using a spectrocolorimeter when the resin sheet (thickness 250 μm) is heated and pressurized at a temperature of 230 ° C. and a pressure of 100 kgf is 20 or less. (2): Using the resin sheet, 3D-2 of standard standards for foods, additives, etc. (Ministry of Health and Welfare Notification No. 370 in 1959), synthetic resin appliances or containers and packaging (category: operating temperature, 100 μC or less), the evaporation residue amount by evaporation residue test (leaching solution: heptane, 20% ethanol, water or 4% acetic acid) was 20 μg / ml regardless of which leaching solution was used. Is

The YI value in the requirement (1) is preferably 14 or less.
A resin sheet having a YI value in the above range is excellent in stability, particularly thermal stability, and can be particularly suitably used for packaging pharmaceutical products.
Specifically, the YI value can be measured by the method described in the Examples below.

The amount of evaporation residue in the requirement (2) is preferably 15 μg / ml or less, more preferably 10 μg / ml or less.
A resin sheet having an evaporation residue amount in the above range has a small bleed-out amount, is excellent in safety, and is difficult to change the efficacy of the drug over a long period of time.

The shape in particular of the resin sheet of this invention is not restrict | limited, What is necessary is just to select suitably according to a desired use.
The thickness of the resin sheet of the present invention is not particularly limited, but is preferably 30 to 500 μm, more preferably 50 to 300 μm from the viewpoint of moldability to a blister pack.

  The resin sheet of the present invention contains the following resin (B), and when the resin (B) is a vinyl chloride resin, the compound (I) represented by the following formula (I) or a tautomer thereof (hereinafter referred to as the following) It is preferable that the compound (I) and its tautomer are also referred to as “compound (A)”.

<Resin (B)>
The resin (B) contained in the resin sheet of the present invention is not particularly limited as long as it is a conventionally known resin used for a resin sheet for pharmaceutical packaging. Examples of such resin (B) include ester resins (polyester) such as polyethylene terephthalate and polyethylene naphthalate, olefins such as polyethylene, polypropylene, polybutene, ethylene / propylene copolymer, and ethylene / butene copolymer. Examples of the resin include polystyrene, polyamide, vinyl chloride resin (PVC), polycarbonate, polyacrylonitrile, and polyimide. In addition, 1 type may be sufficient as resin (B) contained in the resin sheet of this invention, and 2 or more types may be sufficient as it.

  Among these, a vinyl chloride resin is preferable from the standpoint that the problems of conventional resin sheets for packaging pharmaceuticals can be more solved.

  The vinyl chloride resin is not particularly limited as long as it is a resin obtained from vinyl chloride as a raw material, and examples thereof include a vinyl chloride homopolymer or a vinyl chloride and other monomer and copolymer.

  Although it does not specifically limit as said other monomer, For example, ethylene, propylene, acrylonitrile, vinyl acetate, maleic acid or its ester, acrylic acid or its ester, methacrylic acid or its ester, and vinylidene chloride are mentioned.

The vinyl chloride resin may be a resin in which the homopolymer or copolymer is partially crosslinked. Further, a polymer blend of a vinyl chloride resin, for example, a polymer blend composed of a vinyl chloride resin and polyvinylidene chloride may be used.
Of these, vinyl chloride homopolymers are preferred.

  The average polymerization degree of the vinyl chloride resin measured based on JIS K 6720-2 is preferably 500 to 5000, more preferably from the viewpoint of obtaining a resin sheet excellent in thermal stability and moldability. 500-2000.

  The resin (B) may be a resin synthesized by a conventionally known method or a commercially available product.

<Compound (A)>
By using the compound (A), the bleed is provided with the stability equivalent to or higher than the excellent stability of the conventional stabilizers against deterioration due to heat of the vinyl chloride resin. A resin sheet with a small amount of out, excellent in safety, and excellent in low odor, UV-cutting ability, visible light permeability and transparency can be obtained.
The compound (A) is used in place of the tin-based stabilizer that has recently been found to be toxic, and it has the same or better stability as the tin-based stabilizer, but also has safety and low odor. Such a resin sheet excellent in ultraviolet cutting ability and transparency is useful industrially, particularly in the pharmaceutical packaging field. That is, in this invention, when using a compound (A), it is preferable not to use a tin-type stabilizer.

  Of course, the present inventor not only found these things, but also confirmed that even if the compound (A) was used, there was no problem in safety and it could be used for pharmaceutical packaging.

The compound (A) is also used as a stabilizer for a vinyl chloride resin contained in the resin sheet of the present invention, specifically, a resin stabilization for a low odor polyvinyl chloride sheet for pharmaceutical packaging. Used as an agent.
By using such a compound (A), the bleed-out is maintained while maintaining the stability such as the thermal stability equivalent to or higher than the conventional one without using the tin-based stabilizer used conventionally. It is possible to obtain a resin sheet for packaging pharmaceuticals, which is made of a low-toxic material with a small amount, and particularly has a low odor and an excellent ability to cut off ultraviolet rays.
Furthermore, the resin sheet which can form a blister pack at low temperature can be obtained by using such a compound (A).

  Ketones are one type of compounds that usually cause unpleasant odors, but the reason is not clear in the present invention, but the odor of the resin sheet can be reduced even if such ketones are used.

In the formula (I), R ¹ and R ³ are each independently at least part of an aryl group having 6 to 18 carbon atoms, an alkyl group having 1 to 18 carbon atoms, an aralkyl group having 7 to 18 carbon atoms, and an alkyl group. Is a group substituted with a halogen atom or an oxygen atom (provided that the group has 1 to 18 carbon atoms), a hydroxy group, or a group wherein at least part of the aryl group is substituted with an alkoxy group (provided that The group has 7 to 18 carbon atoms).

  The aryl group having 6 to 18 carbon atoms is preferably an aryl group having 6 to 12 carbon atoms, and examples thereof include a phenyl group, a biphenyl group, and a naphthyl group.

  As said C1-C18 alkyl group, a C1-C12 alkyl group is preferable, and a methyl group, an ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, tert-butyl. Group, n-pentyl group, n-hexyl group, n-heptyl group, n-octyl group and the like.

  The aralkyl group having 7 to 18 carbon atoms is preferably an aralkyl group having 7 to 12 carbon atoms, and examples thereof include a benzyl group, a phenylmethyl group, and a phenylethyl group.

The group in which at least a part of the alkyl group is substituted with a halogen atom or an oxygen atom (provided that the group has 1 to 18 carbon atoms) is preferably a group having 1 to 12 carbon atoms. Examples include groups in which at least a part is substituted with a group such as a hydroxy group, a carboxyl group, or an acyl group. Specifically, —CF ₃ , —CCl ₃ , —O—CH ₃ , —O—C ₂ H ₅ , —CH ₂ COOCH ₃ , —CH ₂ COOC ₂ H _{5 and the} like.

The group in which at least a part of the aryl group is substituted with an alkoxy group (provided that the group has 7 to 18 carbon atoms) is preferably a group having 7 to 12 carbon atoms, -Ph-O-CH ₃ , -Ph-O-C ₂ H ₅ (wherein ph represents a benzene ring).

In the formula (I), R ² is a single bond, an alkylene group or an aralkylene group having 7 to 18 carbon atoms having 1 to 18 carbon atoms.

  The alkylene group having 1 to 18 carbon atoms is preferably an alkylene group having 1 to 12 carbon atoms, more preferably an alkylene group having 1 to 6 carbon atoms, a methylene group, an ethylene group, a methylmethylene group, a propylene group, or a methylethylene group. Dimethylmethylene group, butylene group, methylpropylene group, methylpropylene group and the like.

  The aralkylene group having 7 to 18 carbon atoms is preferably an aralkylene group having 7 to 12 carbon atoms, and examples thereof include a phenylmethylene group, a phenylethylene group, and a phenylpropylene group.

In the formula (I), R ^{1 to} R ³ may be bonded to each other, and R ² may form a dimer. Such compounds include cyclohexane-1,3-dione, bisacetylacetone, 5,5′-dimethylcyclohexane-1,3-dione, 2,2′-methylenebiscyclohexane-1,3-dione, 2-benzyl. And cyclohexane-1,3-dione.

Wherein the compound (I) is more excellent thermal stability and the like, from the viewpoint of the resin sheet excellent in UV ability is obtained, R ¹ and R ³ is an aryl group having 6 to 12 carbon atoms, R ² is The compound (i) which is a C1-C6 alkylene group is preferable, Furthermore, it is excellent in a low odor, heat stability, and ultraviolet-cutting ability, and can use more suitably as a sheet | seat for pharmaceutical packaging. R ¹ and R ³ are each a phenyl group, and compound (ii) in which R ² is a methylene group is more preferred.

  Examples of the tautomer of compound (I) include isomers obtained by keto-enol tautomerism of compound (I).

  As the compound (A), the compound (I), further the compound (i), particularly the compound (ii) is preferable in that a resin sheet excellent in high thermal stability, low odor, and high ultraviolet cutting ability can be obtained. Is preferred.

  As the compound (A), a compound synthesized by a conventionally known method may be used, or a commercially available product may be used.

In the resin sheet of the present invention, the content of the compound (A) is preferably 0.01 to 2.0 parts by mass, more preferably 0.01 to 1. parts by mass with respect to 100 parts by mass of the vinyl chloride resin. It is 0 mass part, More preferably, it is 0.01-0.7 mass part, Most preferably, it is 0.01-0.5 mass part.
When the content of the compound (A) is in the above range, it is possible to obtain a resin sheet having a good balance between high thermal stability, low odor, high ultraviolet ray cutting ability and high transparency, and particularly suitable for blister packs. Can be obtained.

  The compound (A) contained in the resin sheet of the present invention may be one kind alone, or two or more kinds.

<Other components (C)>
The resin sheet of this invention may contain other components (C) other than a compound (A) and resin (B) as needed in the range which does not impair the effect of this invention.

Examples of the other component (C) include antioxidants, stabilizers such as heat stabilizers and light stabilizers, ultraviolet scattering agents, pigments, antistatic agents, lubricants, softeners, plasticizers, and processing aids. It is done.
Each of these other components (C) may be used alone in the resin sheet of the present invention, or two or more may be used in the resin sheet of the present invention.

  When the resin sheet of the present invention contains the compound (A), benzophenone-based UV absorbers, benzotriazole-based UV absorbers, salicylate-based UV absorbers, triazine-based UV absorbers that have been used in conventional resin sheets for packaging pharmaceuticals Even if it does not contain an organic ultraviolet absorber such as an agent and a benzoate ultraviolet absorber, it has a desired ultraviolet cutting ability. Therefore, when the resin sheet of the present invention contains the compound (A), the resin sheet of the present invention absorbs organic ultraviolet rays from the viewpoint of obtaining a resin sheet that is excellent in safety and has few bleed-out components. It is preferable not to contain an agent.

  Further, when the resin sheet of the present invention contains the compound (A), the resin sheet of the present invention absorbs ultraviolet rays when the purpose is to obtain a resin sheet that is excellent in safety and has few bleed-out components. It is preferable not to contain an agent or an ultraviolet scattering agent.

<Softener>
As the softening agent, a softening agent conventionally used for a resin sheet for pharmaceutical packaging can be used, and is not particularly limited. However, from the viewpoint of improving the impact resistance of the resulting resin sheet, butyl acrylate Methyl (meth) acrylate copolymer, butyl acrylate-styrene-methyl (meth) acrylate copolymer, ethylene-vinyl acetate copolymer, methyl methacrylate-butadiene-styrene copolymer, acrylonitrile-butadiene-styrene copolymer, Impact improving resins such as epoxy-modified ethylene-propylene copolymer, styrene-butadiene copolymer, styrene-isoprene copolymer, styrene-ethylene-butylene copolymer, styrene-ethylene-propylene copolymer are preferred.

<Plasticizer>
As the plasticizer, a plasticizer conventionally used in a resin sheet for pharmaceutical packaging can be used, and is not particularly limited, but is di-2-ethylhexyl phthalate (DOP), dibutyl phthalate (DBP), diheptyl phthalate. Phthalate plasticizers such as (DHP) and diisodecyl phthalate (DIDP); fatty acid ester plasticizers such as di-2-ethylhexyl adipate (DOA), diisobutyl adipate (DIBA) and dibutyl adipate (DBA); epoxidized linseed Oil, epoxidized soybean oil, epoxidized castor oil, epoxidized safflower oil, epoxidized linseed oil fatty acid butyl, epoxidized ester plasticizer such as octyl epoxy stearate; tri-2-ethylhexyl trimellitate (TOTM), Triisononyl trimellite Trimellitate ester plasticizer such bets (TINTM); trimethyl phosphate (TMP), and phosphoric acid ester-based plasticizers such as triethyl phosphate (TEP) and the like. Among these, an epoxidized ester plasticizer is preferable from the viewpoint of moldability and workability of the resin sheet.

<Lubricant>
Examples of the lubricant include those conventionally used for pharmaceutical packaging resin sheets, and are not particularly limited, and examples thereof include dimethylpolysiloxane, fatty acid alcohol ester, low molecular weight polyethylene, and the like. From these points, fatty acid alcohol esters are preferred.
The fatty acid alcohol ester is preferably a 1-3-valent ester compound of glycerin and a fatty acid, for example, stearic acid monoglyceride, stearic acid diglyceride, stearic acid triglyceride lubricant, oleic acid glyceride lubricant, Examples include palmitate glyceride lubricants.

<Processing aid>
As the processing aid, processing aids conventionally used for pharmaceutical packaging resin sheets can be used, although not particularly limited, such as methyl methacrylate / ethyl acrylate copolymer, high molecular weight polymethyl methacrylate, etc. Acrylic processing aids are preferred.

<Stabilizer>
As the stabilizer, a stabilizer conventionally used in a resin sheet for pharmaceutical packaging can be used, and is not particularly limited, but a metal compound such as lithium, sodium, potassium, magnesium, calcium, aluminum, barium, and zinc , Organic phosphites, polyhydric alcohols, phenolic compounds, epoxy compounds, organic phosphite compounds, calcium, barium, zinc, etc. from the point of obtaining resin sheets with excellent safety and stability These metal compounds are preferred.

<Method for producing resin sheet>
The resin sheet of the present invention is formed, for example, by molding a resin composition containing the compound (A), the resin (B) and, if necessary, other components (C) into a sheet shape by a known method such as a melt molding method. Can be manufactured.

<Multilayer sheet>
The resin sheet of the present invention may be used as a single layer of the sheet, but if necessary, on one or both sides of the resin sheet of the present invention, a gas barrier layer such as an oxygen barrier layer, a gas absorption layer, a moisture-proof layer, a light shielding layer You may use as a multilayer sheet in which layers, such as a layer and a bleed out prevention layer, were laminated.

  The multilayer sheet can be produced by a method similar to a conventionally known laminate production method. For example, the multilayer sheet is heat-sealed after the sheets forming the respective layers are superposed on one or both sides of the resin sheet of the present invention, or the sheets forming the respective layers are bonded via an adhesive layer or the like. It can be manufactured by sticking. Here, in order to improve the interlayer adhesion of the resulting multilayer sheet, the surface of any layer forming the multilayer sheet is pretreated with corona treatment, low temperature plasma treatment, ion bombardment treatment, chemical treatment, solvent treatment, etc. You may pre-process by the method of.

  Further, the multilayer sheet uses, for example, a multilayer T using a resin composition containing a compound (A), a resin (B) and, if necessary, another component (C), and a composition forming each layer. Manufactured by a general multilayer sheet molding method such as a die extrusion method or a multilayer extrusion method, extrusion coating, dry lamination, heat lamination, a casting method such as a wet casting method or a dry casting method, or a calendar method. You can also.

  The thickness of the multilayer sheet may be appropriately selected depending on the desired application, but is usually in the range of 150 μm to 500 μm, preferably 180 μm to 350 μm. With such a thickness, a blister pack can be produced from the multilayer sheet with good moldability.

<Blister pack>
Since the resin sheet of the present invention is excellent in stability such as thermal stability and has a small amount of bleed out, a blister pack can be easily formed. In addition, when the resin sheet of the present invention contains the compound (A), it is difficult to generate odor even if heat is applied, and it is difficult to generate odor residue in the pocket. The blister pack can be manufactured with a low temperature, and because it is excellent in moldability at low temperature, a blister pack with low manufacturing cost and excellent transparency can be easily obtained. Furthermore, when the resin sheet of this invention contains a compound (A), since a blister pack can be shape | molded at low temperature, generation | occurrence | production of the odor which is easy to occur in the case of high temperature shaping | molding, and the fall of film performance can be suppressed.

  A method for producing a blister pack from the resin sheet of the present invention or the multilayered sheet is not particularly limited. For example, pockets are formed by a known molding method, medicines are loaded into each pocket, and the loaded medicines are sealed. As described above, a blister pack can be produced by adhering the resin sheet of the present invention or the multilayer sheet and a sealing material (lid material).

Here, the method of forming a pocket in the resin sheet of the present invention or the multilayer sheet specifically includes the following methods.
・ Heat and pressure molding method: The resin sheet of the present invention or the multilayer sheet is sandwiched between a lower mold having holes to which high-temperature and high-pressure air is supplied and an upper mold having pocket-shaped recesses, and heated and softened. A method of forming pockets by supplying air while a pre-heater flat plate pressure forming method: a lower die having holes for supplying high-pressure air after heating and softening the resin sheet of the present invention or the multilayer sheet. And the upper mold having a pocket-shaped recess and supplying air to form a pocket. Drum-type vacuum forming method: the resin sheet of the present invention or the multilayer sheet has a pocket-shaped recess. A method of forming a pocket by vacuuming the recess after partially heating and softening with a heating drum-Pin forming method: After heating and softening the resin sheet of the present invention or the multilayer sheet, pocketing A method of pressure bonding with a concave-convex mold of a G-shape ・ Preheater plug-assisted pressure forming method: a lower mold having holes to which high-pressure air is supplied after heating and softening the resin sheet of the present invention and the multilayer mold sheet A method of forming a pocket by sandwiching it between an upper die having a pocket-shaped concave portion and supplying air to assist the molding by raising and lowering the convex plug during molding.

  In addition, the shape, size, depth, number, arrangement, etc. of the pocket portion of the blister pack can be appropriately selected depending on the shape and use of the pharmaceutical product.

  As the sealing material (lid material), a material having a heat-sealable resin layer is preferable because the loaded contents can be sealed by heat sealing (heating adhesion). The heat-sealable resin layer is not particularly limited as long as it is a layer that is fused with the resin sheet of the present invention loaded with a pharmaceutical product or the multilayer sheet at the time of heat-sealing. For example, low-density polyethylene (LDPE) , Medium density polyethylene (MDPE), high density polyethylene (HDPE), linear low density polyethylene (LLDPE), ethylene vinyl acetate copolymer (EVA), polypropylene (PP), ethylene / acrylic acid copolymer (EAA), Ethylene / methacrylic acid copolymer (EMA), ethylene / methyl acrylate copolymer (EMAA), ethylene / ethyl acrylate copolymer (EEA), ethylene / methyl methacrylic acid copolymer (EMMA), ionomer (IO) ) And the like are included.

  Moreover, it is preferable that a sealing material (cover material) has metal vapor deposition film layers, such as an aluminum layer, and a metal foil layer from the point that gas-barrier property is favorable.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated more concretely, this invention is not limited by these. The resin sheets of the following examples and comparative examples are the vinyl chloride resin, the compound (A) or the tin stabilizer, as well as the other components (C) that have been conventionally used in pharmaceutical packaging resin sheets. In particular, among these, it can manufacture using a preferable component.

[Example 1]
Polyvinyl chloride 85.6% by weight, impact resistance improving resin 8% by weight, plasticizer 4% by weight, lubricant 1% by weight, processing aid 0.6% by weight, stabilizer 0.5% by weight and dibenzoylmethane 0 The resin composition was obtained by mixing 3 mass%. Using the obtained resin composition, a resin sheet having a thickness of about 250 μm was prepared by calendar molding.

[Example 2]
In Example 1, a resin sheet was prepared in the same manner as in Example 1 except that the calendering conditions were changed so that the thickness of the obtained resin sheet was about 200 μm.

[Comparative Example 1]
In Example 1, a resin sheet having a thickness of about 250 μm was prepared in the same manner as in Example 1 except that 0.3% by mass of dioctyltin was used instead of 0.3% by mass of dibenzoylmethane.

[Comparative Example 2]
In Comparative Example 1, a resin sheet was prepared in the same manner as in Comparative Example 1, except that the calendering conditions were changed so that the thickness of the resulting resin sheet was about 200 μm.

<Stability>
The thermal stability of the resin sheets of Example 1 and Comparative Example 1 was measured by the following method. The results are shown in Table 1.
Using a hot press machine, the resin sheets of Example 1 and Comparative Example 1 were heated and pressed for 3 minutes under the conditions of a heating temperature of 220 to 260 ° C. and a pressing pressure of 100 kgf, and the state of the pressed sheet was visually confirmed. The case where there was no deformation or discoloration before and after hot pressing was evaluated as “◯”, and the case where discoloration occurred was evaluated as “x”.
Thereafter, the YI value of the sheet after hot pressing was measured using a spectrocolorimeter (Konica Minolta Co., Ltd., CM-2600d).

  Table 1 shows that the resin sheet of an Example shows the heat resistance of the same level or more compared with the conventional resin sheet (resin sheet of a comparative example).

<Safety (bleed out amount)>
The safety of the resin sheet of Example 1 is determined based on the standard D of food and additives (Ministry of Health and Welfare Notification No. 370 of 1959), 3D-2, synthetic resin equipment or container packaging (category: operating temperature) , 100 ° C. or less).

The resin sheet of an Example became the analysis result shown in Table 2, and it turned out that it is excellent in safety.
In addition, the resin sheet of the example has an evaporation residue amount of 10 μg / ml in the case of using any of the heptane, 20% ethanol, water or 4% acetic acid leaching solutions as the leaching solution. The following shows that the amount of bleed out is extremely small.

  It is not until the analytical test for safety as shown in Table 2 is it determined whether or not the resin sheet can be used for pharmaceutical packaging. Sheets for packaging pharmaceutical products are required to be safe.

<Ultraviolet / visible light transmission>
The total light transmittance of the resin sheets of Example 1 and Comparative Example 1 was measured using an ultraviolet-visible spectrophotometer (V-560 manufactured by JASCO Corporation). Specifically, test pieces each having a size of 10 × 40 mm were cut out from the resin sheets of Example 1 and Comparative Example 1, and the test pieces were used to emit light having a wavelength of 220 to 780 nm with the ultraviolet-visible spectrophotometer. The transmittance was measured. The results are shown in FIG.

  From FIG. 1, the resin sheet of an Example has fully cut | disconnected ultraviolet-ray (220-380 nm) compared with the conventional resin sheet (resin sheet of a comparative example), and also visible-light (400-780 nm) transmittance | permeability. It is understood that it is excellent.

<Haze>
The haze of the resin sheets of Example 1 and Comparative Example 1 was measured using an ultraviolet-visible spectrophotometer (V-560 manufactured by JASCO Corporation). Specifically, test pieces each having a size of 10 × 40 mm were cut out from the resin sheets of Example 1 and Comparative Example 1, and the total light transmittance and diffusion were measured with the UV-visible spectrophotometer using the test pieces. The light transmittance was measured, and the haze was calculated from these values.

The haze of the resin sheet of Example 1 was about 0.8%, and the haze of the resin sheet of Comparative Example 1 was about 1.5%.
From the above results, it can be seen that the resin sheet of the example has a small haze value and excellent transparency as compared with the conventional resin sheet (resin sheet of the comparative example).

<Odor>
The odors of the resin sheets of Example 2 and Comparative Example 2 were measured by the following method.
From each of the resin sheets of Example 2 and Comparative Example 2, 2.0 g test pieces were cut out, and the test pieces were sealed in gas chromatography vials made by PerkinElmer, each having a capacity of 22 mL. The sample was heated with a space sampler (HSS) at 140 ° C. for 5 minutes, and 600 μL of the gas generated by the heating was automatically injected into the GC / MS, and the gas generated from each specimen was analyzed. The analysis conditions for GC / MS (gas chromatography mass spectrometry) are as shown in Table 3 below.

  Table 4 shows the results of the odor test. In Table 4, the numerical value in the left column of each test indicates the peak area of each gas component, and the numerical value in the right column indicates the ratio (%) of each generated gas component when the peak area of air is 100%. . ● and ▲ are substances with high odor intensity, and ● (organic acid) is about 100 times stronger than ▲ (aromatics, etc.).

From the resin sheets of Example 2 and Comparative Example 2, no sulfur compounds such as hydrogen sulfide, methyl sulfide, and mercaptan with strong odor intensity were detected.
From the resin sheet of Comparative Example 2, 2-Ethyl-hexanoic acid and 2-Propyl-1-pentanol were detected as substances having strong odor intensity. However, 2-Ethyl-hexanoic acid was detected from the resin sheet of Example 2. It was not detected, the amount of 2-Propyl-1-pentanol generated was reduced to 1/3 or less, and the total amount of gas generated was also reduced to 10 ppc or less.
From the above analysis results, it can be seen that the resin sheet of the example generates less odor than the conventional resin sheet (resin sheet of the comparative example).

<Blister pack formability>
The blister pack moldability of the resin sheets obtained in Example 1 and Comparative Example 1 was evaluated by the following method. The results are shown in Table 5.
The moldability of the blister pack was measured using the resin sheet of Example 1 and Comparative Example 1 in a PTP molding machine (manufactured by CKD Corporation, FBP-M2) by using a pinpoint heating plate as shown in Table 5 below. After heating at Φ11.0 × H4.0 tablet mold (diameter 11 mmφ, depth 4.0 mm) and a plug assist mechanism, the resulting resin sheet mold at each temperature (tablet mold) The mold following ability was evaluated. In addition, the mold followability evaluated the external appearance nonuniformity of the pocket top part, the corner part, and the side part by visual observation.

  Further, the resin sheet having the pocket portion obtained at the above (heating temperature 120 ° C.) is sealed with aluminum foil, and after slitting the obtained blister pack, it is punched into a width 50 mm, a length 108 mm, and a corner R 5 mm. It was. The appearance of the resulting molded product was evaluated for the appearance of the die, which is the bonded portion between the aluminum foil and the resin sheet.

From Table 5, it turns out that the resin sheet of an Example can be shape | molded at low temperature compared with the conventional resin sheet (resin sheet of a comparative example), and is excellent in low temperature moldability.
In addition, it can be seen that the aluminum sealability is comparable to that of the conventional resin sheet (the resin sheet of the comparative example) without the appearance of the die and the tearing of the aluminum foil.

Claims (5)

A resin sheet for pharmaceutical packaging that satisfies the following requirements (1) and (2).
Requirement (1): YI value (yellow index) measured with a spectrocolorimeter when the resin sheet for pharmaceutical packaging (thickness: 250 μm) is heated and pressurized at a temperature of 230 ° C. and a pressure of 100 kgf is 20 or less. Requirement (2): Using the above-mentioned resin sheet for packaging pharmaceuticals, 3D-2 of standard standards for foods, additives, etc. (Ministry of Health and Welfare Notification No. 370 of 1959), synthetic resin appliances or containers and packaging (Category: Operating temperature, 100 ° C or less) Measured based on evaporation residue test (leaching solution: heptane, 20% ethanol, water or 4% acetic acid) 20 μg / ml or less   The resin sheet for pharmaceutical packaging according to claim 1, wherein the resin includes a vinyl chloride resin. The resin sheet for medical packaging of Claim 2 containing the compound (I) represented by the following formula (I), or its tautomer.

(In the formula (I), R ¹ and R ³ are each independently at least part of an aryl group having 6 to 18 carbon atoms, an alkyl group having 1 to 18 carbon atoms, an aralkyl group having 7 to 18 carbon atoms, and an alkyl group. Is a group substituted with a halogen atom or an oxygen atom (provided that the group has 1 to 18 carbon atoms), a hydroxy group, or a group wherein at least part of the aryl group is substituted with an alkoxy group (provided that The group has 7 to 18 carbon atoms.), R ² is a single bond, an alkylene group having 1 to 18 carbon atoms or an aralkylene group having 7 to 18 carbon atoms, and R ^{1 to} R ³ are It may be bonded, and a dimer may be formed in R ^2. )   The resin sheet for medical packaging of Claim 3 whose content of the said compound (I) or its tautomer with respect to 100 mass parts of vinyl chloride resin is 0.01-2.0 mass parts.   The resin sheet for packaging pharmaceuticals according to any one of claims 1 to 4, which is a sheet for blister packs for packaging pharmaceuticals.

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