WO2016002686A1 - 医薬品容器及び医薬品製剤 - Google Patents
医薬品容器及び医薬品製剤 Download PDFInfo
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- WO2016002686A1 WO2016002686A1 PCT/JP2015/068612 JP2015068612W WO2016002686A1 WO 2016002686 A1 WO2016002686 A1 WO 2016002686A1 JP 2015068612 W JP2015068612 W JP 2015068612W WO 2016002686 A1 WO2016002686 A1 WO 2016002686A1
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- Prior art keywords
- resin
- pharmaceutical
- manufactured
- pharmaceutical container
- cyclic olefin
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/14—Details; Accessories therefor
- A61J1/1468—Containers characterised by specific material properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
- A61J1/10—Bag-type containers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K5/00—Use of organic ingredients
- C08K5/04—Oxygen-containing compounds
- C08K5/07—Aldehydes; Ketones
Definitions
- the present invention relates to a pharmaceutical container and a pharmaceutical preparation.
- prefilled syringe preparations in which a syringe is prefilled with a medicine are known.
- Polypropylene resins, cyclic olefin resins, and the like are used as materials used in the syringe barrel of this type of prefilled syringe preparation.
- cyclic olefin-based resins are preferably used from the viewpoints of transparency, chemical resistance, and the like (Patent Document 1, etc.).
- Patent Documents 2 and 3 a method of covering a syringe filled with a medicine with a light-shielding label and a method of storing a prefilled syringe in a light-shielding package have been proposed.
- the present invention has been made in view of the above-mentioned problems and the like, and an object thereof is to provide a pharmaceutical container having excellent transparency and ultraviolet light shielding properties, and a pharmaceutical preparation provided with the pharmaceutical container.
- the present invention has been made in order to solve the above-described problems, and provides a pharmaceutical container formed of a resin composition containing a cyclic olefin resin and a dibenzoylmethane compound.
- the dibenzoylmethane-based compound is 2-methyldibenzoylmethane, 4-methyldibenzoylmethane, 4-isopropyldibenzoylmethane, 4-tert-butyldibenzoylmethane, 2,4-dimethyldibenzoyl.
- the dibenzoylmethane compound may be 4-tert-butyl-4′-methoxydibenzoylmethane.
- the content of the dibenzoylmethane compound may be 0.01% by weight or more and 5.0% by weight or less in the resin composition.
- the drug container may be a syringe, a vial, an ampoule, or an infusion bag.
- the present invention also provides a pharmaceutical preparation comprising the above pharmaceutical container, wherein the pharmaceutical container is filled with a medicine.
- FIG. 1A shows a front view of a prefilled syringe formulation according to one embodiment of the present invention.
- FIG. 1B shows a cross-sectional view taken along line AA of FIG. 1A.
- FIG. 2 is a diagram showing the light transmittance in the wavelength region 220 to 780 nm of the resin plates A1 to A4.
- FIG. 3 is a diagram showing light transmittance in the wavelength region 220 to 440 nm of the resin plates B1 to B7.
- FIG. 4 is a view showing the light transmittance in the wavelength region 220 to 440 nm of the resin plates B8 to B14.
- FIGS. 1A and 1B an embodiment of a pharmaceutical container and a pharmaceutical preparation according to the present invention will be described with reference to FIGS. 1A and 1B.
- the pharmaceutical preparation according to this embodiment is a prefilled syringe preparation provided with a syringe barrel as a pharmaceutical container.
- the prefilled syringe preparation includes a cylindrical syringe barrel 1 filled with a medicine X, a cap 2 attached to the tip of the syringe barrel 1, and an injection. And a plunger 3 that is inserted into the cylinder 1 and is slidable in the axial direction of the syringe cylinder 1.
- the plunger 3 In the prefilled syringe preparation, when the plunger 3 is pushed, the plunger 3 slides in the syringe barrel 1 toward the tip of the syringe barrel 1, and the medicine filled in the syringe barrel 1 is discharged from the tip of the syringe barrel 1. It is configured to be extruded.
- the syringe barrel 1 includes a cylindrical syringe barrel main body 11 having a nozzle portion at the tip, and a finger hook portion 12 that is disposed in a flange shape at the proximal end of the syringe barrel main body 11 and is used to hang a finger.
- the syringe barrel body 11 is filled with a medicine X.
- the syringe barrel 1 of the present embodiment is formed of a resin composition that includes a cyclic olefin resin and a dibenzoylmethane compound. Thereby, the syringe barrel 1 of the present embodiment can have excellent transparency and ultraviolet light shielding properties.
- the thickness of the thinnest portion (side wall portion) of the syringe barrel body 11 is usually 0.5 mm to 3.0 mm. Moreover, the capacity
- the cap 2 includes a sealing portion 21 that seals the nozzle portion provided at the tip of the syringe barrel main body 11, and a cylindrical cap body 22 that fixes the sealing portion 21 while the sealing portion 21 is disposed inside. With.
- the cap 2 includes a cylindrical connection portion 23 that attaches the cap body 22 to the inner peripheral portion.
- the sealing part 21 is formed of a resin such as rubber, for example.
- the cap body 22 and the connection part 23 are formed of, for example, a plastic resin.
- the plunger 3 includes a gasket 31 that is inserted into the syringe barrel body 11 to seal the medicine X filled in the syringe barrel body 11, and a plunger rod 32 that is screw-coupled to the gasket 31 at the tip.
- the gasket 31 is formed of an elastic body such as rubber or thermoplastic elastomer, for example.
- the plunger rod 32 is made of, for example, a plastic resin.
- Examples of the drug X include a liquid agent, a granular agent composed of powder, a solid agent, a powder agent, and the like.
- the liquid agent is not limited to an aqueous solution, and includes a suspension, an oily liquid, and the like.
- the resin composition constituting the syringe barrel 1 of the present embodiment includes a cyclic olefin resin as a main component. Thereby, the transparency and chemical resistance of the syringe barrel 1 can be improved.
- Examples of the cyclic olefin-based resin include general materials for pharmaceutical containers such as a cyclic olefin polymer (COP) and a cyclic olefin copolymer (COC).
- Examples of the COP include a COP containing a repeating unit represented by the following formula (1) and a COP containing a repeating unit represented by the following formula (2).
- Examples of commercially available COPs include “ZEONEX” manufactured by ZEON Corporation and “ZEONOR” manufactured by ZEON Corporation.
- Examples of the COC include a COC containing a repeating unit represented by the following formula (3), a COC containing a repeating unit represented by the following formula (4), and a COC containing a repeating unit represented by the following formula (5).
- Commercially available COCs include “Appel” manufactured by Mitsui Chemicals, “Topas” manufactured by Polyplastics, and the like. These can be used individually by 1 type or in combination of 2 or more types.
- R ′ and R ′′ represent a hydrocarbon group, and n is an integer of 1 or more.
- n is an integer greater than or equal to 1.
- R, R ′ and R ′′ represent a hydrocarbon group, and m, m ′ and n are integers of 1 or more.
- the content of the cyclic olefin-based resin is preferably 90% by weight or more, more preferably 95% by weight or more in the resin composition constituting the syringe barrel 1 from the viewpoint of transparency, chemical resistance, moisture resistance, and the like. More preferably by weight. Moreover, 99.99 weight% or less is preferable, 99.98 weight% or less is more preferable, and 99.95 weight% or less is further more preferable.
- the glass transition temperature (Tg) of the cyclic olefin resin is preferably 115 ° C. or higher, more preferably 121 ° C. or higher, and even more preferably 129 ° C. or higher, from the viewpoint that deformation due to high-pressure steam sterilization does not easily occur. Moreover, from a viewpoint of a moldability, 300 degrees C or less is preferable, 250 degrees C or less is more preferable, and 200 degrees C or less is further more preferable. In the present specification, the glass transition temperature (Tg) can be determined based on the method described in Japanese Industrial Standard (JIS) K7121: 1987 “Method for Measuring Transition Temperature of Plastic”.
- JIS Japanese Industrial Standard
- the resin composition constituting the syringe barrel 1 of the present embodiment includes a dibenzoylmethane compound.
- a dibenzoylmethane compound that is an ultraviolet absorber By containing a dibenzoylmethane compound that is an ultraviolet absorber, the syringe barrel 1 is imparted with ultraviolet light shielding properties without lowering the transparency of the syringe barrel 1, and ultraviolet rays (wavelength region: 220) are provided inside the syringe barrel 1. ⁇ 380 nm) can be suppressed.
- dibenzoylmethane compounds examples include 2-methyldibenzoylmethane, 4-methyldibenzoylmethane, 4-isopropyldibenzoylmethane, 4-tert-butyldibenzoylmethane, 2,4-dimethyldibenzoylmethane, 2 , 5-dimethyldibenzoylmethane, 4,4'-diisopropyldibenzoylmethane, 4,4'-dimethoxydibenzoylmethane, 4-tert-butyl-4'-methoxydibenzoylmethane, 2-methyl-5-isopropylpyroxy 4'-methoxydibenzoylmethane, 2-methyl-5-tert-butyl-4'-methoxydibenzoylmethane, 2,4-dimethyl-4'-methoxydibenzoylmethane, 2,6-dimethyl-4-tert- And butyl
- the content of the dibenzoylmethane compound is preferably 0.01% by weight or more, more preferably 0.05% by weight or more in the resin composition constituting the syringe barrel 1 from the viewpoint of ultraviolet light shielding properties. Further, from the viewpoint of transparency and elution, 5.0% by weight or less is preferable, and 0.6% by weight or less is more preferable.
- the resin composition constituting the syringe barrel 1 of the present embodiment further includes, for example, a stabilizer, a pigment, a dye, an anti-blocking agent, an antistatic agent, an antioxidant, etc., as long as the effects of the present embodiment are not significantly impaired. You may contain.
- the syringe barrel 1 of this embodiment is manufactured by, for example, mixing the components constituting the resin composition and molding the mixture by a normal molding method such as injection molding, press molding, or extrusion molding.
- a cap 2 is attached to the tip of the syringe barrel 1 in an aseptic environment, and a sterilized drug is placed in the syringe barrel 1. It is obtained by attaching the plunger 3 for filling and sealing the medicine filled in the syringe barrel 1.
- the pharmaceutical container according to the present invention is formed of a resin composition containing a cyclic olefin resin and a dibenzoylmethane compound.
- the pharmaceutical preparation according to the present invention comprises the above-mentioned pharmaceutical container, and the medicine is filled inside the pharmaceutical container.
- a pharmaceutical container that is excellent in transparency and has an ultraviolet light shielding property, and a pharmaceutical preparation including the pharmaceutical container.
- the prefilled syringe preparation syringe was adopted as the pharmaceutical container.
- the present invention is not limited to this, and examples of the pharmaceutical container include injections such as general syringe barrels, vials, ampoules, and infusion bags. Any container that directly contacts the drug, such as a drug container, can be applied.
- the prefilled syringe preparation is adopted as the pharmaceutical preparation.
- the pharmaceutical preparation is not limited to this, and the pharmaceutical preparation includes the above-described pharmaceutical container and the medicine container is filled with the medicine. If so, all are applicable.
- an injection needle may be attached to the tip of the syringe barrel.
- Test A the relationship between the concentration of the UV absorber and the light transmittance was evaluated as follows. First, resin plates A1 to A4 (10 mm ⁇ 40 mm ⁇ 1 mm) made of a resin composition comprising the following components were prepared. Then, the total light transmittance was measured using an ultraviolet / visible spectrophotometer (“V-650” manufactured by JASCO Corporation). The measurement results are shown in FIG. In addition, content of each component added as a ultraviolet absorber shows content of each component with respect to the whole resin composition (same also in the following tests).
- Resin plate A1 Cyclic olefin resin (COP, manufactured by Nippon Zeon Co., Ltd., trade name “ZEONEX 690R”) + UV absorber (4-tert-butyl-4′-methoxydibenzoylmethane (hereinafter also referred to as avobenzone), contained (Amount: 0.1% by weight)
- Resin plate A2 Cyclic olefin resin (COP, manufactured by Nippon Zeon Co., Ltd., trade name “ZEONEX 690R”) + UV absorber (Avobenzone, content: 0.68% by weight)
- Resin plate A3 Cyclic olefin resin (COP, manufactured by Nippon Zeon Co., Ltd., trade name “ZEONEX 690R”) + ultraviolet absorber (Zinc oxide, manufactured by Sakai Chemical Industry Co., Ltd., trade name “NANOFINE 50A”, content: 0.68 weight%)
- Resin plate A4 Cyclic olefin resin (COP, manufactured by
- the resin plates A1 to A3 to which the ultraviolet absorber was added were able to substantially block light (ultraviolet rays) in the wavelength region of 220 to 380 nm. Further, the resin plate A1 having a low content of avobenzone exhibited substantially the same ultraviolet light shielding property as the resin plate A2 having a high content of avobenzone. In other words, it was found that avobenzone is excellent in ultraviolet absorption even in a small amount.
- the resin plates A1 and A2 to which avobenzone is added as an ultraviolet absorber have higher light (visible light) transmittance in the wavelength region (380 to 780 nm) than the resin plate A3 to which zinc oxide is added as an ultraviolet absorber. It was confirmed that it was excellent in transparency.
- Test B the ultraviolet light shielding effect by various ultraviolet absorbers was examined as follows. First, resin plates B1 to B14 (thickness: 1 mm) made of a resin composition comprising the following components were prepared. Then, the central part of each resin plate B1 to B14 was cut into a size of 10 mm ⁇ 40 mm. Then, the total light transmittance was measured using an ultraviolet / visible spectrophotometer (“V-650” manufactured by JASCO Corporation). The light transmittance at wavelengths of 220 to 440 nm for the resin plates B1 to B7 is shown in FIG. FIG. 4 shows the light transmittance of the resin plates B8 to B14 at wavelengths of 220 to 440 nm. 3 and 4, the peak areas of the resin plates B1 to B6 and B8 to B13 at wavelengths of 220 to 380 nm were obtained and shown in Table 1.
- Resin plate B1 Cyclic olefin resin (COP, manufactured by Nippon Zeon Co., Ltd., trade name “ZEONEX 690R”) + UV absorber (Avobenzone, content: 0.1% by weight)
- Resin plate B2 Cyclic olefin resin (COP, manufactured by Nippon Zeon Co., Ltd., trade name “ZEONEX 690R”) + benzophenone ultraviolet absorber (manufactured by BASF, “Chimassorb 81”, content: 0.1% by weight)
- Resin plate B3 Cyclic olefin resin (COP, manufactured by Nippon Zeon Co., Ltd., trade name “ZEONEX 690R”) + benzoate UV absorber (manufactured by BASF, “Tinvin 120”, content: 0.1% by weight)
- Resin plate B4 Cyclic olefin resin (COP, manufactured by Nippon Zeon Co., Ltd., trade name “ZEONEX 690R”) + benzotriazole ultraviolet absorb
- the resin plates B1 and B8 to which avobenzone was added had less peak areas at wavelengths of 220 to 380 nm than the resin plates B2 to B6 and B9 to B13 to which other ultraviolet absorbers were added. It was. From this, it was found that avobenzone is superior in ultraviolet absorptivity compared with other ultraviolet absorbers. In addition, as shown in FIGS. 3 and 4, it was confirmed that avobenzone has a transmittance slope near vertices in the vicinity of a wavelength of 380 to 400 nm as compared with other ultraviolet absorbers. In addition, it was confirmed that avobenzone hardly absorbs light in the visible light region of 400 nm or more as compared with other ultraviolet absorbers. That is, it was found that the transparency of the resin plate is hardly lowered.
- Resin plate C1 Cyclic olefin resin (COP, manufactured by Nippon Zeon Co., Ltd., trade name “ZEONEX 690R”) + UV absorber (Avobenzone, content: 0.1% by weight)
- Resin plate C2 Cyclic olefin resin (COP, manufactured by Nippon Zeon Co., Ltd., trade name “ZEONEX 690R”) + UV absorber (Zinc oxide, manufactured by Sakai Chemical Industry Co., Ltd., trade name “NANOFINE 50A”, content: 0.68 weight%)
- Resin plate C3 Cyclic olefin resin (COP, manufactured by Zeon Corporation, trade name “ZEONEX 690R”)
- Resin plate C4 Cyclic olefin resin (COP, manufactured by Nippon Zeon Co., Ltd., trade name “ZEONEX 690R”) + UV absorber (Avobenzone, content: 0.6% by weight)
- each test piece was dried at room temperature. Then, each test piece was put in a flask (volume: about 300 mL), 200 mL of purified water was added accurately, and the flask was sealed. And after heating at 121 degreeC for 1 hour using a high pressure steam sterilizer, it was left until it became room temperature, and this content liquid was used as each test liquid.
- the results of the foaming test are shown in Table 2.
- Table 3 The results of the pH test are shown in Table 3.
- ⁇ Potassium permanganate reducing substance detection test 20 mL of the test solution was taken in a stoppered Erlenmeyer flask, and after adding 20.0 mL of 0.002 mol / L potassium permanganate solution and 1 mL of dilute sulfuric acid, the flask was capped and boiled for 3 minutes. After cooling the flask with water, 0.10 g of potassium iodide solution was added and sealed, mixed well, and allowed to stand for 10 minutes. Thereafter, 5 drops of starch reagent was added as an indicator and titrated with 0.01 mol / L sodium thiosulfate solution. Also, 20 mL of the blank test solution was operated in the same manner as the test solution.
- ⁇ Ultraviolet absorption spectrum absorption substance detection test The absorbance of the test solution was measured using a spectrophotometer with the blank test solution as a control. Here, fixed wavelength measurement of four wavelengths of 220 nm, 240 nm, 241 nm, and 350 nm was performed. And it was determined as appropriate if the absorbance at a wavelength of 220 nm or more and less than 241 nm was 0.08 abs or less and the absorbance at a wavelength of 241 nm or more and 350 nm or less was 0.05 abs or less.
- the results of the ultraviolet absorption spectrum absorbing substance detection test are shown in Table 5.
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Abstract
Description
本実施形態の注射筒1を構成する樹脂組成物は、環状オレフィン系樹脂を主成分として含む。これにより、注射筒1の透明性及び耐薬品性を向上させることができる。
本明細書において、ガラス転移温度(Tg)は、日本工業規格(JIS)K7121:1987「プラスチックの転移温度測定方法」に記載されている方法に基づいて求めることができる。
本実施形態の注射筒1を構成する樹脂組成物は、ジベンゾイルメタン系化合物を含む。紫外線吸収剤であるジベンゾイルメタン系化合物を含むことによって、注射筒1の透明性を低下させずに、注射筒1に紫外線遮光性を付与し、注射筒1の内部に紫外線(波長領域:220~380nm)が透過するのを抑制することができる。
本実施形態の注射筒1を構成する樹脂組成物は、本実施形態の効果を著しく損ねない範囲において、例えば、安定剤、顔料、染料、ブロッキング防止剤、帯電防止剤、酸化防止剤等をさらに含有していてもよい。
本実施形態の注射筒1は、例えば、上記樹脂組成物を構成する各成分を混合し、射出成形、プレス成形、押出成形等の通常の成形方法により成形することにより製造される。
本実施形態のプレフィルドシリンジ製剤は、例えば、本実施形態の注射筒1を滅菌処理した後、無菌環境下で、注射筒1の先端にキャップ2を取り付け、注射筒1内に滅菌済みの薬剤を充填し、注射筒1内に充填された薬剤を封止するためにプランジャ3を取り付けることにより得られる。なお、滅菌処理は、本実施形態の注射筒1に薬剤を充填した後に行ってもよい。この場合、注射筒1への薬剤の充填や、キャップ2及びプランジャ3の取り付けは、無菌環境下で行わなくてもよい。
また、上記実施形態において、医薬品製剤としてプレフィルドシリンジ製剤が採用されたが、これに限定されず、医薬品製剤としては、上述した医薬品容器を備え、該医薬品容器の内部に薬剤が充填されているものであれば全て適用可能である。
試験Aでは、次のようにして紫外線吸収剤の濃度と光透過率との関係を評価した。まず、下記に示す成分からなる樹脂組成物で構成された樹脂プレートA1~A4(10mm×40mm×1mm)を準備した。そして、紫外・可視分光光度計(日本分光社製の“V-650”)を用いて全光線透過率を測定した。測定結果を図2に示した。なお、紫外線吸収剤として添加した各成分の含有量は、樹脂組成物全体に対する各成分の含有量を示したものである(以下の試験においても同様)。
樹脂プレートA2:環状オレフィン系樹脂(COP、日本ゼオン社製、商品名“ZEONEX 690R”)+紫外線吸収剤(アボベンゾン、含有量:0.68重量%)
樹脂プレートA3:環状オレフィン系樹脂(COP、日本ゼオン社製、商品名“ZEONEX 690R”)+紫外線吸収剤(酸化亜鉛、堺化学工業社製、商品名“NANOFINE 50A”、含有量:0.68重量%)
樹脂プレートA4:環状オレフィン系樹脂(COP、日本ゼオン社製、商品名“ZEONEX 690R”)
また、アボベンゾンの含有量が少ない樹脂プレートA1は、アボベンゾンの含有量が多い樹脂プレートA2と略同じ紫外線遮光性を示していた。つまり、アボベンゾンは少量であっても紫外線吸収性に優れることが分かった。
紫外線吸収剤としてアボベンゾンが添加された樹脂プレートA1及びA2では、紫外線吸収剤として酸化亜鉛が添加された樹脂プレートA3に比べて波長領域(380~780nm)における光(可視光)の透過率が高いことが確認され、透明性に優れていることが分かった。
試験Bでは、次のようにして各種紫外線吸収剤による紫外線遮光効果について検討した。まず、下記に示す成分からなる樹脂組成物で構成された樹脂プレートB1~B14(厚さ:1mm)を準備した。そして、各樹脂プレートB1~B14の中央部を10mm×40mmの大きさに切り出した。そして、紫外・可視分光光度計(日本分光社製の“V-650”)を用いて全光線透過率を測定した。樹脂プレートB1~B7についての波長220~440nmにおける光透過率を図3に示した。また、樹脂プレートB8~B14についての波長220~440nmにおける光透過率を図4に示した。そして、図3及び図4において、波長220~380nmにおける樹脂プレートB1~B6、B8~B13のピーク面積を求め、表1に示した。
樹脂プレートB2:環状オレフィン系樹脂(COP、日本ゼオン社製、商品名“ZEONEX 690R”)+ベンゾフェノン系紫外線吸収剤(BASF社製、“Chimassorb81”、含有量:0.1重量%)
樹脂プレートB3:環状オレフィン系樹脂(COP、日本ゼオン社製、商品名“ZEONEX 690R”)+ベンゾエート系紫外線吸収剤(BASF社製、“Tinuvin120”、含有量:0.1重量%)
樹脂プレートB4:環状オレフィン系樹脂(COP、日本ゼオン社製、商品名“ZEONEX 690R”)+ベンゾトリアゾール系紫外線吸収剤(BASF社製、“Tinuvin326”、含有量:0.1重量%)
樹脂プレートB5:環状オレフィン系樹脂(COP、日本ゼオン社製、商品名“ZEONEX 690R”)+トリアジン系紫外線吸収剤(BASF社製、“Tinuvin1577ED”、含有量:0.1重量%)
樹脂プレートB6:環状オレフィン系樹脂(COP,日本ゼオン社製、商品名“ZEONEX 690R”)+ベンゾフェノン系紫外線吸収剤(BASF社製、“Uvinul3049”、含有量:0.1重量%)
樹脂プレートB7:環状オレフィン系樹脂(COP、日本ゼオン社製、商品名“ZEONEX 690R”)
樹脂プレートB8:環状オレフィン系樹脂(COC、ポリプラスチックス社製、商品名“TOPAS6013S-04”)+紫外線吸収剤(アボベンゾン、含有量:0.1重量%)
樹脂プレートB9:環状オレフィン系樹脂(COC、ポリプラスチックス社製、商品名“TOPAS6013S-04”)+ベンゾフェノン系紫外線吸収剤(BASF社製、“Chimassorb81”、含有量:0.1重量%)
樹脂プレートB10:環状オレフィン系樹脂(COC、ポリプラスチックス社製、商品名“TOPAS6013S-04”)+ベンゾエート系紫外線吸収剤(BASF社製、“Tinuvin120”、含有量:0.1重量%)
樹脂プレートB11:環状オレフィン系樹脂(COC、ポリプラスチックス社製、商品名“TOPAS6013S-04”)+ベンゾトリアゾール系紫外線吸収剤(BASF社製、“Tinuvin326”、含有量:0.1重量%)
樹脂プレートB12:環状オレフィン系樹脂(COC、ポリプラスチックス社製、商品名“TOPAS6013S-04”)+トリアジン系紫外線吸収剤(BASF社製、“Tinuvin1577ED”、含有量:0.1重量%)
樹脂プレートB13:環状オレフィン系樹脂(COC、ポリプラスチックス社製、商品名“TOPAS6013S-04”)+ベンゾフェノン系紫外線吸収剤(BASF製、“Uvinul3049”、含有量:0.1重量%)
樹脂プレートB14:環状オレフィン系樹脂(COC、ポリプラスチックス社製、商品名“TOPAS6013S-04”)
また、図3、図4に示すように、アボベンゾンは、他の紫外線吸収剤に比べて、波長380~400nm付近における透過率の傾きが垂直に近いことが確認された。また、アボベンゾンは、他の紫外線吸収剤に比べて、400nm以上の可視光領域の光はほとんど吸収しないことが確認された。つまり、樹脂プレートの透明性をほとんど低下させないことが分かった。
医薬品容器、特に注射剤容器には、該容器内に充填される薬剤の安全性、安定性に影響を与えないように、日本薬局方の「プラスチック製水性注射剤容器の規格」に適合することが求められる。そのため、下記に示す溶出物試験を行い、「プラスチック製水性注射剤容器の規格」を満たしているかを評価した。
まず、下記に示す成分からなる樹脂組成物で構成された樹脂プレートC1~C4(80.0mm×50.0mm×1.0mm)を準備し、それぞれの樹脂プレートのできるだけ厚さが均一な部分をとって切断した。厚さは約1mmであった。
樹脂プレートC2:環状オレフィン系樹脂(COP、日本ゼオン社製、商品名“ZEONEX 690R”)+紫外線吸収剤(酸化亜鉛、堺化学工業社製、商品名“NANOFINE 50A”、含有量:0.68重量%)
樹脂プレートC3:環状オレフィン系樹脂(COP、日本ゼオン社製、商品名“ZEONEX 690R”)
樹脂プレートC4:環状オレフィン系樹脂(COP、日本ゼオン社製、商品名“ZEONEX 690R”)+紫外線吸収剤(アボベンゾン、含有量:0.6重量%)
試験液5mLを、内径約15mm、長さ約200mmの共栓試験管に入れ、3分間激しく振り混ぜ、生じた泡がほとんど消失するまでの時間を測定した。測定時間が3分以内であれば、適正と判定した。泡立ち試験の結果を表2に示した。
試験液及び空試験液を20mLずつ採り、それぞれに濃度0.1%の塩化カリウム1.0mLを加えた。そして、pHメータを使用して、試験液と空試験液のpHを測定し、その差を算出した。算出した差が1.5以下であれば、適正と判定した。pH試験の結果を表3を示した。
試験液20mLを共栓三角フラスコに採り、0.002moL/Lの過マンガン酸カリウム液20.0mL及び希硫酸1mLを加えた後、栓をして3分間煮沸した。フラスコを水で冷却した後、ヨウ化カリウム液0.10gを加えて密栓し、よく混合してから10分間静置した。その後、指示薬としてデンプン試薬5滴を加え、0.01moL/Lのチオ硫酸ナトリウム液で滴定した。
また、空試験液20mLについても、試験液と同様に操作した。
そして、試験液と空試験液の0.002moL/Lの過マンガン酸カリウム液の消費量の差を算出した。消費量の差が1.0mL以下であれば適正と判定した。過マンガン酸カリウム還元性物質検出試験の結果を表4に示した。
試験液の吸光度について、空試験液を対照として分光光度計を用いて測定した。ここでは、220nm、240nm、241nm、350nmの4波長の固定波長測定を行った。そして、波長220nm以上241nm未満における吸光度が0.08abs以下で、かつ、波長241nm以上350nm以下における吸光度が0.05abs以下であれば、適正と判定した。紫外吸収スペクトル吸収物質検出試験の結果を表5に示した。
蒸発皿を感熱し、室温まで徐冷した後、空重量を測定した。そして、試験液10mLを蒸発皿に採り、水浴上で蒸発乾固した。そして、残留物を105℃に設定した恒温槽内で1時間乾燥した。その後、蒸発皿を取り出して室温まで徐冷し、重量を測定した。測定した重量と空重量との差から、蒸発残留物の重量を求めた。試験液10mL中における蒸発残留物の重量が1.0mg以下であれば適正と判定した。蒸発残留物検出試験の結果を表6に示した。
Claims (6)
- 環状オレフィン系樹脂と、ジベンゾイルメタン系化合物と、を含む樹脂組成物によって形成された、医薬品容器。
- 前記ジベンゾイルメタン系化合物は、2-メチルジベンゾイルメタン、4-メチルジベンゾイルメタン、4-イソプロピルジベンゾイルメタン、4-tert-ブチルジベンゾイルメタン、2,4-ジメチルジベンゾイルメタン、2,5-ジメチルジベンゾイルメタン、4,4´-ジイソプロピルジベンゾイルメタン、4,4´-ジメトキシジベンゾイルメタン、4-tert-ブチル-4´-メトキシジベンゾイルメタン、2-メチル-5-イソピロピル-4´-メトキシジベンゾイルメタン、2-メチル-5-tert-ブチル-4´-メトキシジベンゾイルメタン、2,4-ジメチル-4´-メトキシジベンゾイルメタン、及び2,6-ジメチル-4-tert-ブチル-4´-メトキシジベンゾイルメタンから選択される少なくとも一つである、請求項1に記載の医薬品容器。
- 前記ジベンゾイルメタン系化合物は、4-tert-ブチル-4´-メトキシジベンゾイルメタンである、請求項2に記載の医薬品容器。
- 前記ジベンゾイルメタン系化合物の含有量は、上記樹脂組成物中、0.01重量%以上5.0重量%以下である請求項1から3のいずれか1項に記載の医薬品容器。
- 注射筒、バイアル、アンプル、又は輸液バックである請求項1から4のいずれか1項に記載の医薬品容器。
- 請求項1から5のいずれか1項に記載の医薬品容器を備え、前記医薬品容器の内部に薬剤が充填されている、医薬品製剤。
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JP2017197525A (ja) * | 2016-04-22 | 2017-11-02 | ロート製薬株式会社 | 水性組成物 |
CN108883232A (zh) * | 2016-04-25 | 2018-11-23 | 泰尔茂株式会社 | 用于预灌封注射器的注射器主体、注射器装置及预灌封注射器 |
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WO2022187332A1 (en) * | 2021-03-02 | 2022-09-09 | West Pharmaceutical Services, Inc. | Container for a pharmaceutical composition |
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EP3162350A1 (en) | 2017-05-03 |
US20170135900A1 (en) | 2017-05-18 |
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