JP6565435B2 - Propylene resin composition for medical kit preparation for radiation sterilization and medical kit preparation thereof - Google Patents

Description

  The present invention relates to a propylene-based resin composition for a medical kit preparation compatible with radiation sterilization and a medical kit preparation thereof, and more specifically, after the radiation sterilization represented by gamma ray sterilization and electron beam sterilization, 7.02 Test method for plastic drug containers 2. Standards for plastic water-based injection containers 2.1. Polyethylene or polypropylene water-based injection containers ”(hereinafter sometimes referred to as“ Japanese Pharmacopoeia Test ”). ) And a propylene-based resin composition for a medical kit preparation for radiation sterilization that is excellent in processing stability and a medical kit preparation thereof.

Propylene-based polymers are used in various medical devices, taking advantage of their excellent safety and hygiene, molding processability, mechanical properties, and gas barrier properties. In particular, in recent years, the use of metal and glass as an alternative container for foods, drugs, and chemical solutions that require a high level of safety and hygiene has become increasingly common, and materials for such applications have been developed. I have been.
These resins for storage containers are required to have long-term stability as storage containers, and the product performance as a container does not deteriorate due to deterioration within the period of use, and the gas barrier properties of water vapor and oxygen are maintained. It is necessary that the additive does not interact with the contents and contents of the liquid, and in particular, it is essential for medical drugs and chemical storage containers to conform to the test items of the Japanese Pharmacopoeia test. It is a requirement.

  Examples of medical uses that need to conform to the Japanese Pharmacopoeia test include drug solutions, prefilled syringes that are kit preparations pre-filled with drugs, infusion bags, infusion bottles, infusion port members, and the like. In addition, material development for these applications has been conventionally performed (see, for example, Patent Documents 1 to 10).

  Conventionally, however, it has been common to perform autoclave sterilization on containers that need to conform to these Japanese Pharmacopoeia tests. When ethylene oxide gas (EOG) sterilization is performed, there is a concern that EOG will be absorbed into the contents liquid. When radiation sterilization is performed, decomposition of additives mixed in the resin and resin composition constituting the container This is because the amount of eluate increases due to this, and does not conform to the Japanese Pharmacopoeia test after radiation sterilization.

  On the other hand, radiation sterilization has the advantage that a large amount of products can be sterilized in a short time compared to high-pressure steam sterilization. However, for the above reasons, it has been extremely difficult to develop a propylene-based resin composition for medical kit preparations and a medical kit preparation for radiation sterilization.

JP 2008-150571 A JP 2008-150572 A JP 2008-255325 A JP 2008-255326 A JP 2009-120798 A JP 2009-120800 A JP 2009-120803 A JP 2010-121126 A JP 2012-152933 A JP 2014-0543373 A

  The object of the present invention is to provide a “16th revision Japanese Pharmacopoeia 7.02 Test Method for Plastic Drug Containers 2. Standards for Plastic Aqueous Injection Containers 2.1. Another object of the present invention is to provide a propylene-based resin composition for a medical kit preparation capable of radiation sterilization and a medical kit preparation thereof that are compatible with the test item of “or an aqueous injection container made of polypropylene” and have excellent processing stability.

  As a result of intensive studies to solve the above-mentioned problems, the present inventor, as a result of blending a specific antioxidant with a propylene-based polymer, propylene for a medical kit preparation compatible with radiation sterilization compatible with the Japanese Pharmacopoeia test. The present invention has been completed by finding that a resin composition and a medical kit preparation thereof can be obtained.

  That is, according to 1st invention of this invention, it selects from the group which consists of a compound represented by a compound represented by following formula (1), and a formula (2) with respect to 100 weight part of propylene-type polymers. Radiation characterized by containing 0.01 to 1 part by weight of at least one amine-based antioxidant and substantially not containing a phenolic antioxidant and a nucleating agent having an aromatic substituent. Propylene-based resin compositions for sterilization-compatible medical kit formulations are provided.

（式中のＲ^１とＲ^２は、独立してＣ_１２〜Ｃ_１８のアルキル基である。）

(In the formula, R ¹ and R ² are each independently a C _{12 to} C ₁₈ alkyl group.)

（式中のＲ^３とＲ^４は、独立してＣ_１４〜Ｃ_２２のアルキル基である。）

(In the formula, R ³ and R ⁴ are each independently a C ₁₄ -C ₂₂ alkyl group.)

According to the second aspect of the present invention, at least one selected from the group consisting of a compound represented by the following formula (3) and a compound represented by the formula (4) with respect to 100 parts by weight of the propylene-based polymer. Provided is a propylene-based resin composition for medical kit preparation for radiation sterilization according to the first invention, further comprising 0.001 to 1 part by weight of two neutralizing agents.
M ²⁺ _1-x Al ³⁺ _x (OH ⁻ ) ₂ (X ⁿ⁻ ) _{x / n} · mH ₂ O (3)
[Wherein M ²⁺ represents a divalent metal ion selected from the group consisting of Mg ²⁺ , Ca ²⁺ and Zn ²⁺ , X ⁿ⁻ represents an n-valent anion, and x represents 0 <x ≦ 0.5. The number in the range, m is a number in the range of 0 ≦ m ≦ 2, and n is an integer in the range of 1 ≦ n ≦ 3. ]
[Al ₂ Li (OH) ₆ ] _r Y · qH ₂ O (4)
[Y represents an inorganic anion or an organic anion, r represents the valence of Y, and q represents a positive number. ]

  According to the third invention of the present invention, the radiation according to the first or second invention, wherein 0.01 to 1 part by weight of a hindered amine light stabilizer is further blended with 100 parts by weight of the propylene polymer. Propylene-based resin compositions for sterilization-compatible medical kit formulations are provided.

  According to a fourth invention of the present invention, in any one of the first to third inventions, 0.05 to 10 parts by weight of a polymer nucleating agent is further blended with 100 parts by weight of a propylene polymer. The propylene-based resin composition for medical kit preparation for radiation sterilization is provided.

  According to a fifth invention of the present invention, in any one of the first to fourth inventions, 0.01 to 1 part by weight of a phosphorus antioxidant is further blended with 100 parts by weight of the propylene polymer. The propylene-based resin composition for medical kit preparation for radiation sterilization is provided.

  According to the sixth aspect of the present invention, there is provided a medical kit preparation obtained by molding the propylene-based resin composition for a radiation sterilization medical kit preparation according to any one of the first to fifth inventions.

  According to the seventh aspect of the present invention, there is provided the medical kit preparation according to the sixth aspect, wherein the medical kit preparation is radiation sterilized.

  According to the eighth invention of the present invention, there is provided the medical kit formulation according to the sixth or seventh invention, wherein the medical kit formulation is a prefilled syringe, an infusion bag, an infusion bottle or an infusion port member.

  The propylene-based resin composition for medical kit preparation for radiation sterilization according to the present invention can be applied to the "16th revision Japanese Pharmacopoeia 7.02 Plastic Pharmaceutical Container Test Method" after radiation sterilization represented by gamma ray sterilization and electron beam sterilization. 2. Standards for plastic water-based injection containers 2.1. Polyethylene or polypropylene water-based injection containers "The test item" and excellent processing stability.

  The propylene-based resin composition for medical kit preparation for radiation sterilization according to the present invention is composed of a compound represented by the following formula (1) and a compound represented by the formula (2) with respect to 100 parts by weight of the propylene-based polymer. A composition comprising 0.01 to 1 part by weight of at least one amine-based antioxidant selected from the above, and substantially free of a phenolic antioxidant and a nucleating agent having an aromatic substituent And is particularly useful for medical kit formulations.

（式中のＲ^１とＲ^２は、独立してＣ_１２〜Ｃ_１８のアルキル基である。）

(In the formula, R ¹ and R ² are each independently a C _{12 to} C ₁₈ alkyl group.)

（式中のＲ^３とＲ^４は、独立してＣ_１４〜Ｃ_２２のアルキル基である。）

(In the formula, R ³ and R ⁴ are each independently a C ₁₄ -C ₂₂ alkyl group.)

Hereinafter, the components of the composition, the method for producing the composition, the molded product of the composition (medical kit preparation), etc. will be described in detail.
[1] Components constituting a propylene-based resin composition for a medical kit preparation for radiation sterilization Propylene Polymer The propylene polymer used in the propylene resin composition of the present invention may be a propylene homopolymer, a propylene copolymer, or a mixture thereof.
The propylene-based copolymer is a copolymer of propylene and an α-olefin, which may be a random copolymer or a block copolymer, but is a random copolymer from the viewpoint of transparency. Is desirable. Examples of the α-olefin used for copolymerization include α-olefins having 2 to 20 carbon atoms excluding propylene, and examples thereof include ethylene, butene-1, hexene-1, and octene-1. One or more α-olefins copolymerized with propylene may be used. Of these, ethylene and butene-1 are preferred. More preferably, ethylene is suitable.
Specific examples of the copolymer include propylene-ethylene copolymer, propylene-ethylene-diene copolymer, propylene-butene-1 copolymer, propylene-ethylene-butene-1 copolymer, propylene- Examples include hexene-1 copolymers and propylene-octene-1 copolymers. Of these, propylene-ethylene copolymer, propylene-butene-1 copolymer, and propylene-ethylene-butene-1 copolymer are particularly preferable. The constituent ratio of the amount of α-olefin that is propylene and a comonomer is preferably about 70 to 99.9 / 30 to 0.1 in terms of molar ratio. Usually, the amount of α-olefin is preferably 0.05 to 10.0% by weight, more preferably about 0.1 to 5.0% by weight. Of course, a so-called polypropylene polymer alloy in which a rubber component such as EPR is introduced as a soft segment into a hard segment composed of a crystalline phase mainly composed of polypropylene at the polymerization stage can also be used.
As for the glass transition temperature of a propylene polymer, a -100-20 degreeC thing is mentioned.

The propylene polymer used in the present invention has a melt flow rate (MFR) at 230 ° C. and a load of 2.16 kg, preferably 0.01 to 1000 g / 10 min, more preferably 0.05 to 500 g / 10 min. More preferably, it is 0.1-200 g / 10min. When the MFR is in this range, the resin composition has good rigidity and impact resistance, and a resin composition suitable for a high production rate derived from the molding temperature is obtained.
Here, MFR is a value measured under a load of 230 ° C. and 2.16 kg in accordance with JIS K7210.

When a propylene homopolymer is used as the propylene-based polymer, the isotactic pentad fraction (mmmm) is 90% or more, preferably 94% or more, more preferably 97% or more. When the isotactic pentad fraction (mmmm) is 90% or more, rigidity and heat resistance (thermal deformation temperature) are improved, and deformation of the molded product during molding can be prevented.
Here, the isotactic pentad fraction (mmmm) is a value measured by ¹³ C-NMR method.

The amount of α-olefin in the random copolymer in the case of using a propylene random copolymer (hereinafter sometimes referred to as “random copolymer”) as the propylene polymer is preferably 0.1. -10.0% by weight, more preferably 0.1-5.0% by weight. When it is 0.1% by weight or more, the transparency and impact resistance of the propylene random copolymer are good, and when it is 10.0% by weight or less, mechanical properties and moldability are good.
Here, the α-olefin content is a value measured by the IR method using a propylene copolymer whose composition is tested by ¹³ C-NMR as a reference substance.

  When a propylene-based block copolymer comprising a polypropylene segment and a propylene copolymer segment (hereinafter sometimes referred to as a “block copolymer”) is used as the propylene-based polymer, polypropylene occupying the block copolymer The segment is 70 to 99% by weight, the propylene copolymer segment is preferably 1 to 30% by weight, the polypropylene segment is 86 to 98% by weight, and the propylene copolymer segment is 2 to 14% by weight. Is more preferable. Within this range, it is suitable for improving mechanical properties of the resin composition.

At this time, the isotactic pentad fraction (mmmm) of the polypropylene segment is 90% or more, preferably 94% or more, more preferably 97% or more. When the isotactic pentad fraction (mmmm) is 90% or more, the molded product is hardly deformed during molding.
Here, the isotactic pentad fraction (mmmm) is a value measured by ¹³ C-NMR method.

Further, as a propylene polymer, a propylene block obtained by polymerizing an α-olefin-propylene copolymer in the first stage and then polymerizing an α-olefin-propylene copolymer having a different α-olefin content in the second stage. It may be a copolymer (hereinafter also referred to as “block copolymer”).
The total α-olefin content contained in the block copolymer is preferably 0.5 to 12% by weight, and more preferably 2 to 9% by weight. Moreover, as an alpha olefin, the above-mentioned thing can be used preferably and ethylene is especially preferable. When the α-olefin content is within this range, the resulting resin composition has good impact resistance and rigidity.
Here, the α-olefin content is a value measured by the IR method using a propylene copolymer whose composition is tested by ¹³ C-NMR as a reference substance.

  Although it does not specifically limit as a manufacturing method of a propylene polymer, The polymerization method using a stereoregular catalyst is preferable. Examples of stereoregular catalysts include Ziegler catalysts and metallocene catalysts.

  As Ziegler catalysts, transition metal components such as titanium trichloride, titanium tetrachloride, trichloroethoxytitanium, etc., contact materials of the above-mentioned titanium halide compounds and magnesium compounds represented by magnesium halide, and alkylaluminum Compounds or their two-component catalysts with organic metal components such as halides, hydrides, alkoxides, and further, electron-donating compounds containing nitrogen, carbon, phosphorus, sulfur, oxygen, silicon, etc. are added to these components 3 Component-based catalysts can be mentioned.

  The metallocene catalyst includes (i) a transition metal compound belonging to Group 4 of the periodic table (so-called metallocene compound) containing a ligand having a cyclopentadienyl skeleton, and (ii) a stable ionic state by reacting with the metallocene compound. A catalyst comprising an activatable cocatalyst and, if necessary, (iii) an organoaluminum compound, any known catalyst can be used. The metallocene compound is preferably a bridged metallocene compound capable of stereoregular polymerization of propylene, and more preferably a bridged metallocene compound capable of isoregular polymerization of propylene.

  Examples of (i) metallocene compounds include JP-A-60-35007, JP-A-63-130314, JP-A-63-295607, JP-A-1-275609, JP-A-2-41303, and JP-A-2-41303. JP-A-2-131488, JP-A-2-76887, JP-A-3-163888, JP-A-4-30087, JP-A-4-21694, JP-A-5-43616, JP-A-5-209913, JP-A-6 No. 239914, JP-A-7-504934, and JP-A-8-85708.

More specifically, methylene bis (2-methylindenyl) zirconium dichloride, ethylenebis (2-methylindenyl) zirconium dichloride, ethylene 1,2- (4-phenylindenyl) (2-methyl-4-phenyl) -4H-azulenyl) zirconium dichloride, isopropylidene (cyclopentadienyl) (fluorenyl) zirconium dichloride, isopropylidene (4-methylcyclopentadienyl) (3-t-butylindenyl) zirconium dichloride, dimethylsilylene (2- Methyl-4-t-butyl-cyclopentadienyl) (3′-t-butyl-5′-methyl-cyclopentadienyl) zirconium dichloride, dimethylsilylenebis (indenyl) zirconium dichloride, dimethylsilylenebis (4,5 , , 7-tetrahydroindenyl) zirconium dichloride, dimethylsilylenebis [1- (2-methyl-4-phenylindenyl)] zirconium dichloride, dimethylsilylenebis [1- (2-ethyl-4-phenylindenyl)] zirconium Dichloride, dimethylsilylenebis [4- (1-phenyl-3-methylindenyl)] zirconium dichloride, dimethylsilylene (fluorenyl) t-butylamidozirconium dichloride, methylphenylsilylenebis [1- (2-methyl-4, ( 1-naphthyl) -indenyl)] zirconium dichloride, dimethylsilylenebis [1- (2-methyl-4,5-benzoindenyl)] zirconium dichloride, dimethylsilylenebis [1- (2-methyl-4-phenyl-4H) -Azulenyl) ] Zirconium dichloride, dimethylsilylenebis [1- (2-ethyl-4- (4-chlorophenyl) -4H-azurenyl)] zirconium dichloride, dimethylsilylenebis [1- (2-ethyl-4-naphthyl-4H-azurenyl)] Zirconium dichloride, diphenylsilylene bis [1- (2-methyl-4- (4-chlorophenyl) -4H-azulenyl)] zirconium dichloride, dimethylsilylene bis [1- (2-ethyl-4- (3-fluorobiphenylyl) ) -4H-azurenyl)] zirconium dichloride, dimethylgermylenebis [1- (2-ethyl-4- (4-chlorophenyl) -4H-azurenyl)] zirconium dichloride, dimethylgermylenebis [1- (2-ethyl-) 4-phenylindenyl)] zirconium Zirconium compounds such as chloride can be exemplified. In the above, compounds in which zirconium is replaced with titanium or hafnium can be used in the same manner. In some cases, a mixture of a zirconium compound and a hafnium compound can be used. The chloride can be replaced with other halogen compounds, hydrocarbon groups such as methyl, isobutyl and benzyl, amide groups such as dimethylamide and diethylamide, alkoxide groups such as methoxy group and phenoxy group, hydride groups and the like.
Among these, a metallocene compound obtained by crosslinking an indenyl group or an azulenyl group with a silicon or a germyl group is preferable.

The metallocene compound may be supported on an inorganic or organic compound carrier. As the carrier, a porous compound of an inorganic or organic compound is preferable. Specifically, ion-exchanged layered silicate, zeolite, SiO ₂ , Al ₂ O ₃ , silica alumina, MgO, ZrO ₂ , TiO ₂ , B ₂ Examples include inorganic compounds such as O ₃ , CaO, ZnO, BaO, and ThO ₂ , organic compounds composed of porous polyolefin, styrene / divinylbenzene copolymer, olefin / acrylic acid copolymer, and the like, or a mixture thereof. .

  (Ii) As a co-catalyst that can be activated to a stable ionic state by reacting with a metallocene compound, an organoaluminum oxy compound (for example, an aluminoxane compound), an ion-exchange layered silicate, a Lewis acid, a boron-containing compound, an ionic compound And fluorine-containing organic compounds.

  (Iii) Examples of organoaluminum compounds include trialkylaluminum such as triethylaluminum, triisopropylaluminum, triisobutylaluminum, dialkylaluminum halide, alkylaluminum sesquihalide, alkylaluminum dihalide, alkylaluminum hydride, organoaluminum alkoxide. Can be mentioned.

Propylene-based polymers can be produced by a slurry method using an inert solvent, a solution method, a gas phase method substantially using no solvent, or bulk polymerization using a polymerization monomer as a solvent in the presence of the above catalyst. Legal etc. are mentioned.
For example, in the case of the slurry polymerization method, it can be carried out in an inert hydrocarbon or liquid monomer such as n-butane, isobutane, n-pentane, isopentane, hexane, heptane, octane, cyclohexane, benzene, toluene, xylene and the like. . The polymerization temperature is usually −80 to 150 ° C., preferably 40 to 120 ° C. The polymerization pressure is preferably 1 to 60 atmospheres (0.10 to 6.08 MPa), and the molecular weight of the resulting propylene polymer can be adjusted with hydrogen or other known molecular weight regulators. The polymerization is carried out by a continuous or batch reaction, and the conditions may be those usually used. Furthermore, the polymerization reaction may be performed in one stage or in multiple stages.

2. Amine-based antioxidant The amine-based antioxidant to be blended in the propylene-based resin composition for medical kit preparation for radiation sterilization according to the present invention is derived from the compound represented by the formula (1) and the compound represented by the formula (2). At least one amine-based antioxidant selected from the group consisting of:

（式中のＲ^１とＲ^２は、独立してＣ_１２〜Ｃ_１８のアルキル基である。）

(In the formula, R ¹ and R ² are each independently a C _{12 to} C ₁₈ alkyl group.)

（式中のＲ^３とＲ^４は、独立してＣ_１４〜Ｃ_２２のアルキル基である。）

(In the formula, R ³ and R ⁴ are each independently a C ₁₄ -C ₂₂ alkyl group.)

In the formula, preferable R ¹ and R ² are a dodecyl group, a tetradecyl group, a hexadecyl group, and an octadecyl group, and more preferably a hexadecyl group and an octadecyl group. Preferred R ³ and R ⁴ are a tetradecyl group, a hexadecyl group, an octadecyl group, and a docosa group, and more preferred are a hexadecyl group, an octadecyl group, and a docosa group. A commercially available thing can be used as such an amine antioxidant. Specific examples include trade names manufactured by BASF; Irgas tab FS042, Irgas tab FS301FF, and trade names manufactured by ADDIVANT; GENOX EP.

  The compounding amount of the amine-based antioxidant is 0.01 to 1 part by weight, preferably 0.01 to 0.5 part by weight, more preferably 0 to 100 parts by weight of the propylene polymer. 0.02 to 0.4 parts by weight, more preferably 0.05 to 0.35 parts by weight, particularly preferably 0.08 to 0.3 parts by weight, and most preferably 0.1 to 0.2 parts by weight. If it is 0.01 part by weight or more, sufficient antioxidant performance (processing stability) can be obtained, and if it is 1 part by weight or less, it is advantageous in terms of cost effectiveness (cost / performance). Amine antioxidants may be used alone or in combination with a propylene polymer.

3. Neutralizing agent As the neutralizing agent that may be added to the propylene-based resin composition for medical kit preparation for radiation sterilization of the present invention, a compound represented by the following formula (3) and a compound represented by the formula (4) And at least one neutralizing agent selected from the group consisting of:
M ²⁺ _1-x Al ³⁺ _x (OH ⁻ ) ₂ (X ⁿ⁻ ) _{x / n} · mH ₂ O (3)
[Wherein M ²⁺ represents a divalent metal ion selected from the group consisting of Mg ²⁺ , Ca ²⁺ and Zn ²⁺ , X ⁿ⁻ represents an n-valent anion, and x represents 0 <x ≦ 0.5. The number in the range, m is a number in the range of 0 ≦ m ≦ 2, and n is an integer in the range of 1 ≦ n ≦ 3. ]
[Al ₂ Li (OH) ₆ ] _r Y · qH ₂ O (4)
[Y represents an inorganic anion or an organic anion, r represents the valence of Y, and q represents a positive number. ]

  A commercially available neutralizing agent can be used. Specifically, the product name; DHT4A manufactured by Kyowa Chemical Industry Co., Ltd .; the product name manufactured by Kyowa Chemical Industry Co., Ltd .; the product name manufactured by DHT4C, Mizusawa Chemical Industry Co., Ltd .;

  When a neutralizing agent is added to the propylene-based resin composition for medical kit preparation for radiation sterilization of the present invention, it is usually 0.001 to 1 part by weight, preferably 0, per 100 parts by weight of the propylene-based polymer. 0.005 to 1 part by weight, more preferably 0.007 to 0.5 part by weight, still more preferably 0.008 to 0.1 part by weight, particularly preferably 0.01 to 0.05 part by weight, and most preferably 0. 0.012 to 0.03 parts by weight. When it is 0.001 part by weight or more, the performance as a neutralizing agent can be sufficiently exhibited, and when it is 1 part by weight or less, it is advantageous from the viewpoint of cost effectiveness (cost / performance).

4). Hindered amine light stabilizer The propylene-based resin composition for medical kit preparation for radiation sterilization according to the present invention may contain a hindered amine light stabilizer as long as the efficacy is not lost. Representative examples of hindered amine light stabilizers include bis (2,2,6,6-tetramethyl-4-piperidyl) sebacate, poly {[6-[(1,1,3,3-tetramethylbutyl) amino]. -1,3,5-triazine-2,4diyl] [(2,2,6,6-tetramethyl-4-piperidyl) imino] hexamethylene [(2,2,6,6-tetramethyl-4- Piperidyl) imino]}, N, N′-bis (3-aminopropyl) ethylenediamine-2,4-bis [N-butyl-N- (1,2,2,6,6-pentamethyl-4-piperidyl) amino ] -6-chloro-1,3,5-triazine condensate, dimethyl succinate 1- (2-hydroxyethyl) -4-hydroxy-2,2,6,6-tetramethylpiperidine polycondensate, etc. be able to. Among these, high molecular weight represented by dimethyl succinate 1- (2-hydroxyethyl) -4-hydroxy-2,2,6,6-tetramethylpiperidine polycondensate (trade name; manufactured by BASF; Tinuvin 622) Mixing the type is preferable from the viewpoint of low elution.

  When blending a hindered amine light stabilizer into the propylene resin composition for medical kit preparation for radiation sterilization of the present invention, it is preferably 0.01 to 1 part by weight with respect to 100 parts by weight of the propylene polymer. More preferably, it is 0.01-0.9 weight part, More preferably, it is 0.01-0.5 weight part, Especially preferably, it is 0.01-0.2 weight part. If it is 0.01 part by weight or more, long-term thermal stability performance can be sufficiently exhibited, and if it is 1 part by weight or less, it is advantageous from the viewpoint of cost effectiveness (cost / performance).

6). Polymer nucleating agent Examples of the nucleating agent that may be added to the propylene resin composition for medical kit preparation for radiation sterilization of the present invention include polymer nucleating agents. Sorbitol-based nucleating agent (trade name; Gelol MD, manufactured by Shin Nippon Rika Co., Ltd.), nonitol-based nucleating agent (trade name; manufactured by Milliken; Millad NX8000), organophosphoric acid, generally blended with propylene-based polymers When a nucleating agent having an aromatic substituent such as a metal salt nucleating agent (trade name; ADEKA STAB NA-11 and NA-21 manufactured by ADEKA Corporation) is blended, the decomposition of these nucleating agents is caused after radiation sterilization. Due to the increase in eluate, it becomes incompatible with the Japanese Pharmacopoeia. Therefore, the propylene-based resin composition for medical kit preparation for radiation sterilization of the present invention is compatible with the Japanese Pharmacopoeia after radiation sterilization when blended with a polymer-based nucleating agent instead of a conventionally used nucleating agent. In addition, it is possible to obtain a propylene-based resin composition for a medical kit preparation for radiation sterilization that is excellent in transparency as a product.
Examples of the polymer nucleating agent include those having no aromatic substituent and having only a hydrocarbon group. Specifically, polyvinylcyclohexane, poly-3-methyl-1-butene, high density polyethylene, long Examples thereof include chain branched polypropylene. As a representative example of the high-density polyethylene, there can be mentioned a product name; Novatec ^™ HD HJ490P manufactured by Nippon Polyethylene Co., Ltd. Representative examples of the long-chain branched polypropylene include Londel Basel's product name; PF814, Borealis' product name; WB140HMS, Nippon Polypro Co., Ltd. product name; Waymax ^TM MFX3, MFX6 and MFX8.

  When a polymer nucleating agent is added to the propylene resin composition for medical kit preparation for radiation sterilization of the present invention, it is usually 0.05 to 10 parts by weight, preferably 0. 1-9 parts by weight, more preferably 0.2-8 parts by weight, still more preferably 0.3-7 parts by weight, particularly preferably 0.4-6 parts by weight, most preferably 0.5-5 parts by weight. is there. When it is 0.05 parts by weight or more, the performance as a nucleating agent can be sufficiently exerted, and when it is 10 parts by weight or less, the physical properties of the polymer-based nucleating agent itself are propylene resins for radiation sterilization compatible medical kit formulations There is no concern of affecting the physical properties of the composition.

7). Phosphorus antioxidant The propylene resin composition for medical kit preparation for radiation sterilization of the present invention may contain a phosphorus antioxidant within a range not losing its efficacy. Representative examples of phosphorus antioxidants include bis (2,6-di-t-butyl-4-methylphenyl) pentaerythritol-di-phosphite, di-stearyl-pentaerythritol-di-phosphite, bis (2 , 4-Di-t-butylphenyl) pentaerythritol-di-phosphite, bis (2,4-dicumylphenyl) pentaerythritol-di-phosphite, tris (2,4-di-t-butylphenyl) Phosphite, tetrakis (2,4-di-t-butylphenyl) -4,4'-biphenylene-di-phosphonite, tetrakis (2,4-di-t-butyl-5-methylphenyl) -4, 4′-biphenylene-diphosphonite and the like can be mentioned. Among these phosphorus-based antioxidants, tris (2,4-di-t-butylphenyl) phosphite (trade name; Irgafos 168, manufactured by BASF) has performance as a processing stabilizer and hydrolysis resistance of the additive itself. Particularly preferred from the viewpoint of low elution after radiation sterilization.

  When a phosphorus antioxidant is added to the propylene-based resin composition for medical kit preparation for radiation sterilization of the present invention, it is preferably 0.01 to 1 part by weight with respect to 100 parts by weight of the propylene-based polymer. More preferably, it is 0.01-0.9 weight part, More preferably, it is 0.01-0.5 weight part, Especially preferably, it is 0.01 weight part-0.2 weight part. When it is 0.01 part by weight or more, sufficient performance as a processing stabilizer can be obtained, and when it is 1 part by weight or less, after radiation sterilization, the propylene resin composition for medical kit preparation for radiation sterilization is yellowed. This is advantageous in terms of cost effectiveness (cost / performance).

8). Phenol-based antioxidant The propylene-based resin composition for medical kit preparation for radiation sterilization according to the present invention should not substantially contain a phenol-based antioxidant. Specifically, the blending amount of the phenolic antioxidant needs to be less than 0.002 parts by weight, preferably 0 parts by weight, with respect to 100 parts by weight of the propylene polymer. Phenolic antioxidants are generally used for the purpose of suppressing oxidative degradation of resins, but the phenolic antioxidants themselves decompose after radiation sterilization, increasing the amount of eluate and making it incompatible with the Japanese Pharmacopoeia. Was confirmed for the first time. For this reason, the propylene-based resin composition for medical kit preparation for radiation sterilization according to the present invention should not substantially contain a phenol-based antioxidant.
Examples of phenolic antioxidants include tetrakis [methylene-3- (3,5-di-tert-butyl-4-hydroxyphenyl) propionate] methane (trade name: Irganox 1010 manufactured by BASF) and octadecyl-3- ( 3,5-di-tert-butyl-4-hydroxyphenyl) propionate (trade name; Irganox 1076 manufactured by BASF) can be exemplified.

9. Nucleating Agent Having Aromatic Substituent The nucleating agent having an aromatic substituent should not be substantially blended in the propylene-based resin composition for medical kit preparation for radiation sterilization of the present invention. Specifically, the blending amount of the nucleating agent having an aromatic substituent needs to be less than 0.002 parts by weight, preferably 0 parts by weight with respect to 100 parts by weight of the propylene polymer. In general, a nucleating agent is added for the purpose of improving the transparency, rigidity, and molding cycle of propylene-based polymers, but the eluate increases due to decomposition of the nucleating agent having an aromatic substituent after radiation sterilization. It was confirmed for the first time that it was no longer compatible with the Japanese Pharmacopoeia. Therefore, the propylene-based resin composition for medical kit preparation for radiation sterilization according to the present invention should not substantially contain a nucleating agent having an aromatic substituent. Examples of the nucleating agent having an aromatic substituent include a sorbitol nucleating agent (trade name: Gelol MD, manufactured by Shin Nippon Rika Co., Ltd.), a nonitol nucleating agent (trade name: Milad NX8000J, manufactured by Milliken), organophosphorus Examples thereof include acid metal salt nucleating agents (trade names; ADEKA STAB NA-11 and NA-21, manufactured by ADEKA Corporation).

  Further, as other additives, nucleating agents having no aromatic substituent, antistatic agents, slip agents, dispersants such as fatty acid metal salts, dyes, pigments, polyethylene other than high-density polyethylene, olefin elastomers, Styrenic elastomers and the like can be blended within a range that does not impair the object of the present invention. As an example, as a nucleating agent which does not have an aromatic substituent which may be included in the propylene-based resin composition for radiation sterilization medical kit preparation of the present invention, trade names manufactured by Milliken Co .; EXP20E and HPN68L can be exemplified.

[2] Method for Producing Propylene Resin Composition for Radiation Sterilization Compatible Medical Kit Formulation The propylene resin composition for radiation sterilization compatible medical kit formulation of the present invention comprises a propylene polymer, an amine antioxidant, and If necessary, add other additives to a Henschel mixer (trade name), super mixer, ribbon blender, etc., and mix with a normal single screw extruder, twin screw extruder, Banbury mixer, Brabender, roll, etc. It can be obtained by melt-kneading in a temperature range of 190 to 260 ° C.

[3] Manufacturing method of medical kit preparation The medical kit preparation of the present invention is a known method of injection-molding method, extrusion molding method, blow molding method, etc. Although it can be obtained by molding by various molding methods, an injection molding method with high dimensional accuracy and easy to make a complicated shape is desirable.
The medical kit preparation of the present invention is suitable for a syringe barrel and a storage container filled with a drug solution, and is particularly suitable for a prefilled syringe, an infusion bag, an infusion bottle, and an infusion port member. A prefilled syringe is a syringe-shaped preparation that is pre-filled with a chemical solution or a drug, and includes a single chamber type that is filled with one type of liquid and a double chamber type that is filled with two types of drugs. Most prefilled syringes are single-chamber types, but the double-chamber type has a liquid / powder type formulation consisting of powder and its solution and a liquid / liquid type formulation consisting of two types of liquids. Examples of the single chamber type content liquid include a heparin solution. In addition to the radiation sterilization, the medical kit preparation of the present invention may be subjected to a known sterilization treatment such as autoclave sterilization, EOG sterilization, and ultraviolet sterilization.

[4] Sterilization method of medical kit preparation The medical kit preparation of the present invention is sterilized from the viewpoint of hygiene. Examples of the sterilization method include radiation sterilization represented by electron beam sterilization and gamma ray sterilization, high-pressure steam sterilization, EOG sterilization, and ultraviolet sterilization. Among these, radiation sterilization is particularly suitable for the medical kit preparation of the present invention.
These sterilization treatments may be performed after a drug, a chemical solution is filled in a syringe, a bag, or a bottle in advance, or after sterilizing only the container, the drug or the chemical solution may be filled by aseptic filling. Moreover, you may sterilize again after that.
When performing radiation sterilization, it is preferable to perform sterilization in an oxygen-free atmosphere typified by a nitrogen gas atmosphere from the viewpoint of resin degradation, but it may be performed in an air atmosphere.
When performing radiation sterilization, it is generally performed at a dose of 10 kGy (kilo gray) to 50 kGy. An increase in dose more than necessary is not preferable because it may lead to significant deterioration of the resin and an increase in eluate. On the other hand, if the dose is small, sufficient sterilization strength may not be obtained. Therefore, it is preferable to sterilize at a dose of 10 kGy to 50 kGy which is a general range. Among radiation sterilizations, electron beam sterilization is less susceptible to dose deterioration in terms of resin degradation and eluate than gamma sterilization. Therefore, the medical kit preparation of the present invention is particularly preferably electron beam sterilized.
When performing high-pressure steam sterilization, it can be performed in a range from 100 ° C. for boiling to 135 ° C. generally called high retort. When securing the same level of sterilization strength, lowering the sterilization temperature leads to longer sterilization time, so it is not preferable to lower the sterilization temperature more than necessary in order to ensure productivity. On the other hand, it is possible to shorten the sterilization time by raising the sterilization temperature, but this is also not preferable because it leads to alteration of drugs and chemical solutions and deformation of containers. Therefore, the medical kit preparation of the present invention is preferably sterilized at 100 ° C. to 135 ° C., and among them, sterilization at 121 ° C. is particularly preferable from the viewpoint of temperature and time.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited at all by these description. In each example and comparative example, the physical properties used were measured by the following method, and the following were used as the propylene-based polymer, amine-based antioxidant, and other additives.

1. Physical properties and evaluation method (1) Preparation of injection molding test piece for physical property evaluation Using a molding machine with an 80m clamping force of resin pellets, a test piece for evaluating each physical property is prepared by an injection molding method, and a test before radiation sterilization. The pieces were prepared by conditioning for 72 hours in a thermostatic chamber adjusted to a room temperature of 23 ± 5 ° C. and a relative humidity of 50 ± 5% after injection molding.
(2) Preparation of test pieces for Japanese Pharmacopoeia test Using an electric press with a temperature of 230 ° C, the resin pellets were melted at a pressure of 0 kg / cm ² G (gauge pressure, the same applies hereinafter) (0 MPaG) for 7 minutes, and then 70 kg. Compressed for 3 minutes at a pressure of / cm ² G (6.86 MPaG). Thereafter, the sample was quickly moved to a cooling press at 30 ° C. and cooled at a pressure of 120 kg / cm ² G (11.77 MPaG) for 3 minutes to produce a flat plate having a thickness of 0.5 mm and a front and back surface area of 1200 cm ² . The test piece before radiation sterilization was prepared by adjusting the condition for 72 hours in a thermostatic chamber adjusted to a room temperature of 23 ± 5 ° C. and a relative humidity of 50 ± 5% after flat plate molding. The test piece after sterilization with gamma rays was left in a thermostatic chamber adjusted to a room temperature of 23 ± 5 ° C. and a relative humidity of 50 ± 5% for 72 hours after slab forming, and then sterilized in an air atmosphere at an average dose of 25 kGy. It was prepared by conditioning for one week in a thermostatic chamber at room temperature 23 ° C. ± 0.5 ° C. and relative humidity 50 ± 5%. The specimen after electron beam sterilization was left in a thermostatic chamber adjusted to a room temperature of 23 ± 5 ° C. and a relative humidity of 50 ± 5% after flat plate formation for 72 hours, and then sterilized in an air atmosphere at an average dose of 25 kGy. Furthermore, the temperature was adjusted and prepared for one week in a constant temperature room at 23 ° C. ± 0.5 ° C. and a relative humidity of 50 ± 5%.

(3) MFR
The melt flow rate (MFR) of the resin pellets was measured according to JIS K-7210-1999 (230 ° C., 2.16 kg load).
(4) Processing stability Resin pellets were melt-kneaded using a 30 mmΦ single-screw extruder at a temperature of 250 ° C., a screw rotation speed of 100 rpm, an extrusion rate of about 7 kg / hr, and a sample supply hopper under an air atmosphere. Extrusion granulation was performed repeatedly. When the MFR of the resin pellet after two times of extrusion (extrusion number: 1 + 2 = 3 times) is MFR3 and the MFR of the resin pellet before the repetition extrusion (number of extrusion times: 1 time) is MFR1, it is expressed by the following formula. The processing stability was evaluated from ΔMFR. Also, ΔMFR was less than 10 as processing stability (excellent), 10 or more and less than 20 as processing stability (good), and 20 or more as no processing stability (inferior).
ΔMFR = MFR3-MFR1
(5) Flexural modulus The flexural modulus was determined according to JIS K-7171 (ISO178).
(6) Transparency (haze)
An ISO flat plate having a thickness of 1 mm was formed by an injection molding method, and after being molded, left in a temperature-controlled room adjusted to a room temperature of 23 ± 5 ° C. and a relative humidity of 50 ± 5% for 72 hours to adjust the condition, JIS K-7136 ( ISO14782) Determined according to JIS K-7361-1.

(7) 16th revision Japanese Pharmacopoeia (Japanese Pharmacopoeia Exam):
Ashing test and elution according to the test method in the Japanese Pharmacopoeia “7.02 Test method for plastic drug containers 2. Standards for plastic water injection containers, 2.1. Polyethylene or polypropylene water injection containers” The physical test was evaluated. Of the eluate test, for the ultraviolet absorption spectrum, a detailed evaluation result (maximum absorbance) that is the basis for suitability was recorded in accordance with the next section.
However, the sample used for the test was a flat plate having a thickness of 0.5 mm and a surface area of 1200 cm ² prepared in (2), and the ashing test was performed by cutting 5 g of the flat plate. The eluate test was carried out using a flat plate having a thickness of 0.5 mm and a surface area of 1200 cm ^{2 on} the front and back sides, cut into a size of about 5 cm in length and about 0.5 cm in width, washed with pure water, And then put it in a hard glass container having an internal volume of about 300 ml, accurately add 200 ml of pure water, seal with an appropriate stopper, and then heat at 121 ° C. for 1 hour using a high-pressure steam sterilizer. This was left as it was at room temperature, and this content solution was used as a test solution. Separately, pure water was prepared in the same manner with pure water. And the Japanese Pharmacopoeia 2.1. Of the specifications of polyethylene or polypropylene aqueous injection containers, the product was evaluated as “Compliant” if all of the ashing test and the eluate test were satisfied, and “Non-conforming” if one item was not compatible.
(7.1) Japanese Pharmacopoeia Ultraviolet absorption spectrum:
The test solution prepared in accordance with the evaluation procedure of the 16th revision Japanese Pharmacopoeia (7) above and the blank test solution, with the blank test solution as a control, in accordance with the Japanese Pharmacopoeia 2.24 UV-Visible Absorbance Measurement Method The maximum absorbance in the sections of wavelengths 220 to 240 nm and 241 to 350 nm was recorded.
Japanese Pharmacopoeia 2.1. The standard of the polyethylene or polypropylene aqueous injection container is that the maximum absorbance at a wavelength of 220 nm or more and less than 241 nm is 0.08 or less, and the maximum absorbance at a wavelength of 241 nm or more and 350 nm or less is 0.05 or less.

2. Materials used (1) Propylene polymer (i) Propylene homopolymer (HPP): Novatec MA3Q (trade name, manufactured by Nippon Polypro Co., Ltd.), Catalyst: Ziegler catalyst, MFR: 10 g / 10 min, isotactic pen Tad fraction: 0.96 (measured by ¹³ C-NMR).
(Ii) Ethylene / propylene random copolymer (RPP1): Novatec MX03ZQ (trade name, manufactured by Nippon Polypro Co., Ltd.), catalyst: Ziegler catalyst, ethylene content: 3.8% by weight, MFR: 30 g / 10 min ( iii) Ethylene / propylene random copolymer (RPP2): Wintech WSX02P (trade name, manufactured by Nippon Polypro Co., Ltd.), catalyst: metallocene catalyst, ethylene content: 3.4% by weight, MFR: 25 g / 10 min

(2) Amine antioxidant (i) Oxidation product of Bis (Hydrogenated tallow alkyl) amines (Oxidation product of bis (hydrogenated tallow alkyl) amine, trade name manufactured by BASF; FS042): Formula (1) below Equivalent to

（式中のＲ^１とＲ^２は、独立してＣ_１２〜Ｃ_１８のアルキル基である。）
（ｉｉ）Ａｍｉｎｅｓ， ｂｉｓ（ｈｙｄｒｏｇｅｎａｔｅｄ ｒａｐｅ―ｏｉｌ ａｌｋｙｌ）ｍｅｔｈｙｌ， Ｎ―ｏｘｉｄｅｓ（ビス（水添菜種油アルキル）メチルアミンオキシド、ＡＤＤＩＶＡＮＴ社製 商品名；ＧＥＮＯＸ ＥＰ）：下記式（２）に相当

(In the formula, R ¹ and R ² are each independently a C _{12 to} C ₁₈ alkyl group.)
(Ii) Amines, bis (hydrogenated rape-oil alkyl) methyl, N-oxides (bis (hydrogenated rapeseed oil alkyl) methylamine oxide, trade name manufactured by ADDIVANT; GENOX EP): equivalent to the following formula (2)

（式中のＲ^３とＲ^４は、独立してＣ_１４〜Ｃ_２２のアルキル基である。）

(In the formula, R ³ and R ⁴ are each independently a C ₁₄ -C ₂₂ alkyl group.)

(3) Neutralizing agent (i) Magnesium aluminum composite hydroxide (trade name; DHT4C, manufactured by Kyowa Chemical Industry Co., Ltd.): equivalent to the following chemical formula (3) M ²⁺ _1-x Al ³⁺ _x (OH ⁻ ) ₂ ( X ⁿ⁻ ) _{x / n} · mH ₂ O (3)
[Wherein M ²⁺ represents a divalent metal ion selected from the group consisting of Mg ²⁺ , Ca ²⁺ and Zn ²⁺ , X ⁿ⁻ represents an n-valent anion, and x represents 0 <x ≦ 0.5. The number in the range, m is a number in the range of 0 ≦ m ≦ 2, and n is an integer in the range of 1 ≦ n ≦ 3. ]
(Ii) Aluminum lithium composite hydroxide (trade name; Mizukarak manufactured by Mizusawa Chemical Co., Ltd.): equivalent to the following chemical formula (4) [Al ₂ Li (OH) ₆ ] _r Y · qH ₂ O (4) )
[Y represents an inorganic anion or an organic anion, r represents the valence of Y, and q represents a positive number. ]
(4) Hindered amine light stabilizer (i) Dimethyl succinate 1- (2-hydroxyethyl) -4-hydroxy-2,2,6,6-tetramethylpiperidine polycondensate (trade name; manufactured by BASF; Tinuvin 622)
(5) Polymer nucleating agent (i) High-density polyethylene (trade name; Novatec ^TM HD HJ490P manufactured by Nippon Polyethylene Co., Ltd.)
(Ii) Long-chain branched polypropylene (trade name: Waymax ^TM MFX8, manufactured by Nippon Polypro Co., Ltd.)
(6) Nucleating agent having no aromatic substituent (i) 1,2-Cyclohexanedical acid, calcium salt (trade name; EXP20E manufactured by Milliken)
(Ii) CIS-ENDO-BICYCLO (2.2.1) HEPTANE-2,3-DICARBOXYLICACID, DISODIUMMSALT (trade name, manufactured by Milliken; HPN68L)
(7) Phosphorous antioxidant (i) Tris (2,4-di-t-butylphenyl) phosphite (trade name: Irgafos 168 manufactured by BASF)
(8) Phenol antioxidant (i) Tetrakis [methylene-3- (3,5-di-tert-butyl-4-hydroxyphenyl) propionate] methane (trade name; Irganox 1010, manufactured by BASF)
(Ii) Octadecyl-3- (3,5-di-t-butyl-4-hydroxyphenyl) propionate (trade name; Irganox 1076, manufactured by BASF)
(9) Nucleating agent having aromatic substituent (i) 2,4,8,10-Tetra (tert-butyl) -6-hydroxy-12H-dibenzo [d, g] [1,3,2] diophaphosphocin 6-oxide, sodium salt (trade name; ADEKA STAB NA-11, manufactured by ADEKA Corporation)
(Ii) Bis (4-propylbenzylidene) propylene sorbitol (trade name; MILLAD NX8000J, manufactured by Milliken)

(Examples 1-14, Comparative Examples 1-8)
Propylene-based polymer, amine-based antioxidant and other additives (neutralizing agent, nucleating agent, antioxidant, etc.) are prepared in the blending ratios (parts by weight) shown in Table 1, and 3 minutes with a super mixer. After dry blending, using a 35 mmφ twin screw extruder, the temperature is 200 ° C., the screw rotation speed is 200 rpm, the extrusion rate is about 15 kg / hr, and the sample supply hopper is melt-kneaded in a nitrogen atmosphere, pelletized, and resin pellets ( Extrusion frequency: 1 time). Thereafter, resin pellets were molded to prepare various test pieces. And it evaluated using each of a resin pellet and various test pieces. The evaluation results are shown in Table 1.

From Table 1, in Examples 1 to 14 which are the propylene-based resin compositions for medical kit preparations corresponding to radiation sterilization of the present invention that satisfy the respective regulations in the configuration of the present invention, the Japanese Pharmacopoeia even after electron beam and gamma ray sterilization It is clear that Examples 8 to 10, and 13 and 14 are further blended with a propylene-based resin composition for medical kit preparation for radiation sterilization of the present invention and a polymer-based nucleating agent, and are excellent in transparency and also after radiation sterilization. It can be seen that it is compatible with the Japanese Pharmacopoeia. Furthermore, Examples 11 and 12 are those in which a nucleating agent having no aromatic substituent is further blended in the propylene-based resin composition for medical kit preparation for radiation sterilization of the present invention, which is also excellent in transparency, and It can be seen that it is compatible with the Japanese Pharmacopoeia after radiation sterilization.
On the other hand, since Comparative Examples 1 to 4 do not contain an amine-based antioxidant, it is clear that resin degradation cannot be suppressed at the time of radiation sterilization, and is not compatible with the Japanese Pharmacopoeia after radiation sterilization. Comparative Examples 5 and 6 contain an amine-based antioxidant and a phenol-based antioxidant, and may not be compatible with the Japanese Pharmacopoeia due to an increase in eluate due to the decomposition of the phenol-based antioxidant after radiation sterilization. It is clear from the comparison with Example 3. Comparative Examples 7 and 8 were formulated with an amine antioxidant and a nucleating agent having an aromatic substituent, and the amount of eluate increased due to decomposition of the nucleating agent after radiation sterilization, resulting in the Japanese Pharmacopoeia. It is also clear from the comparison with Example 3 that it is not suitable.

Claims (8)

0.01 to at least one amine-based antioxidant selected from the group consisting of the compound represented by the following formula (1) and the compound represented by the formula (2) with respect to 100 parts by weight of the propylene-based polymer. It is blended 1 part by weight, and, by molding a substantially blended, such decoction Radiation sterilization corresponding medical kit preparation for the propylene-based resin composition nucleating agent having a phenolic antioxidant and an aromatic substituent A medical kit preparation obtained by filling a drug solution .

(In the formula, R ¹ and R ² are each independently a C _{12 to} C ₁₈ alkyl group.)

(In the formula, R ³ and R ⁴ are each independently a C ₁₄ -C ₂₂ alkyl group.) 0.001 to 1 weight of at least one neutralizing agent selected from the group consisting of the compound represented by the following formula (3) and the compound represented by the formula (4) with respect to 100 parts by weight of the propylene-based polymer. medical kit from agent according to claim 1, part further contain composed.
M ²⁺ _1-x Al ³⁺ _x (OH ⁻ ) ₂ (X ⁿ⁻ ) _{x / n} · mH ₂ O (3)
[Wherein M ²⁺ represents a divalent metal ion selected from the group consisting of Mg ²⁺ , Ca ²⁺ and Zn ²⁺ , X ⁿ⁻ represents an n-valent anion, and x represents 0 <x ≦ 0.5. The number in the range, m is a number in the range of 0 ≦ m ≦ 2, and n is an integer in the range of 1 ≦ n ≦ 3. ]
[Al ₂ Li (OH) ₆ ] _r Y · qH ₂ O (4)
[Y represents an inorganic anion or an organic anion, r represents the valence of Y, and q represents a positive number. ] Propylene to 100 parts by weight of the polymer, medical kit made agent according to claim 1 or 2 hindered amine light stabilizer made by 0.01 to 1 part by weight further formulation. Propylene to 100 parts by weight of the polymer, medical kit made agent according to claim 1, the polymeric nucleating agent made by 0.05 to 10 parts by weight further formulation. Propylene to 100 parts by weight of the polymer, medical kit made agent according to claim 1, the phosphorus-based antioxidant formed by 0.01 to 1 part by weight further formulation. The medical kit preparation according to any one of claims 1 to 5 , wherein the medical kit preparation is sterilized by radiation. The medical kit formulation meets the test items of “16th revised Japanese Pharmacopoeia 7.02 Test method for plastic drug containers 2. Plastic water injection container standards 2.1. Polyethylene or polypropylene water injection container” The medical kit preparation according to any one of claims 1 to 6. The medical kit preparation according to any one of claims 1 to 7 , wherein the medical kit preparation is a prefilled syringe, an infusion bag, an infusion bottle, or an infusion port member.