JP2016121219A - Propylene-based resin composition for medical use and molded article thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a propylene-based resin composition for medical use satisfying test sections of (4) heavy metal, (5) lead, (6) cadmium, (7) ignition residue and (8) eluate of 2.1 Polyethylene-made or Polypropylene-made Aqueous Injection Container of 2. Specification of Plastic Aqueous Injection Container in 7.02 Plastic Pharmaceutical Container Test Method in The Japanese Pharmacopoeia, Sixteenth Edition, holding excellent heat resistance, rigidity, impact resistance, injection moldability and transparency and suitable for a molded article for medical use and provide the molded article thereof.SOLUTION: There is provided a propylene-based resin composition for medical use, containing 100 pts.wt. of a propylene resin consisting of (A) a propylene (co)polymer which is a propylene single polymer polymerized by a Ziegler Natta catalyst or a propylene copolymer consisting of propylene and α-olefin with the content of less than 1 wt.% and having melt flow rate according to JIS K7210 (230°C, 2.16 kg load) of 0.5 to 100 g/10 min. of 60 to 99 pts.wt. and (B) a propylene-ethylene block copolymer polymerized by the Ziegler Natta catalyst and satisfying properties of (B-i) to (B-iv) of 1 to 40 pts.wt. and 0.005 to 0.3 pts.wt. of a nucleating agent and used by a high pressure steam sterilization.SELECTED DRAWING: None

Description

  The present invention relates to a medical propylene-based resin composition and a molded product thereof, and in particular, among medical-use drugs and chemical storage containers, in particular, the 16th revision Japanese Pharmacopoeia 7.02 Plastic Pharmaceutical Container Testing Method. Standards for plastic water injection containers 2.1 Polyethylene or polypropylene water injection containers (4) heavy metals, (5) lead, (6) cadmium, (7) ignition residue, (8) eluate The present invention relates to a medical propylene-based resin composition suitable for a medical molded product that satisfies test items, and a molded product 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, as a storage container for drugs and chemical solutions that require a high level of safety and hygiene, it has been increasingly used as an alternative container material for ampoules and vials, and materials for such applications are being actively developed. (For example, refer to Patent Document 1).
In such storage containers, the heat resistance, devitrification resistance, additive extraction resistance, and gas barrier properties of water vapor and oxygen during steam sterilization are maintained, and the additives used interact with preservatives and chemicals. It is necessary to have no effect. Specifically, the 16th revision Japanese Pharmacopoeia 7.02 Test method for plastic drug containers Satisfying the specifications for plastic water-based injection containers is an essential requirement.

  The propylene-based polymer is preferably a propylene homopolymer in terms of rigidity, heat resistance and gas barrier properties, and a random copolymer with ethylene in terms of transparency and impact resistance. Although used appropriately and selectively, when used in a storage container, it is difficult to exert sufficient performance in terms of transparency and rigidity with only a propylene-based polymer. Various attempts have been made to optimize the essential performance.

However, for example, when a sorbitol-based transparent nucleating agent was used, it did not satisfy the additive extraction resistance and the Japanese Pharmacopoeia test, and was unsuitable for these applications. In addition, with the addition of aluminum or organophosphate synthetic nucleating agent, the expression of transparency is not sufficient, or when the amount added is increased, satisfactory results are obtained for the ignition residue in the Japanese Pharmacopoeia test. I couldn't.
Examples of medical uses that require passing a Japanese Pharmacopoeia test include kit preparations such as prefilled syringes that are pre-filled with a drug solution.
It was around the mid 1980s (for example, refer to Patent Document 2) that the production of a kit preparation filled with this chemical solution in advance with polypropylene began to be studied (for example, see Patent Document 2). Studies have been conducted on a preparation (for example, see Patent Document 3) in which a drug solution is filled in a transparent syringe barrel or a transparent container made of a nucleating agent.
Since July 1, 2014, Japan has joined the PIC / S (The Pharmaceutical Inspection Convention and the Pharmaceutical Inspection Co-operation Scheme (PIC / S)), so it is managed at the world standard level. In the future, sterilization strength and the like will be required, and materials that can be sterilized at higher temperatures are required. However, after sterilization, it has high transparency satisfying the transmittance of 55% or more described in the Japanese Pharmacopoeia, excellent in heat resistance, rigidity and impact resistance, passed the Japanese Pharmacopoeia test, and used as a storage container for drugs and chemicals At present, satisfactory molded products have not been obtained.

JP-A-1-178541 JP-A-62-194866 JP-A-5-222078

  In view of the above problems, the object of the present invention is the 16th revision Japanese Pharmacopoeia 7.02 Plastic Drug Container Testing Method. Standards for plastic water injection containers 2.1 Polyethylene or polypropylene water injection containers (4) heavy metals, (5) lead, (6) cadmium, (7) ignition residue, (8) eluate An object of the present invention is to provide a medical propylene-based resin composition that satisfies the test items and that retains excellent heat resistance, rigidity, impact resistance, injection moldability, and transparency, and a molded product thereof.

  As a result of intensive studies to solve the above-mentioned problems, the present inventor satisfied the test items of the Japanese Pharmacopoeia by using a specific amount of a nucleating agent for two specific propylene polymers, and was excellent. The inventors have found that a medical propylene-based resin composition that retains heat resistance, rigidity, impact resistance, injection moldability, and transparency and can be sterilized by high-pressure steam can be obtained, and the present invention has been completed.

That is, a propylene homopolymer polymerized by a Ziegler-Natta catalyst or a propylene-based copolymer composed of propylene and an α-olefin having a content of less than 1% by weight, JIS K7210 (230 ° C., 2.16 kg load) 60 to 99 parts by weight of a propylene-based (co) polymer (A) having a melt flow rate (hereinafter sometimes abbreviated as MFR) in conformity with the standard of 0.5 to 100 g / 10 min, and the following (B- Nucleation for 100 parts by weight of a propylene-based resin comprising 1 to 40 parts by weight of a propylene-ethylene block copolymer (B) polymerized by a Ziegler-Natta catalyst satisfying the characteristics i) to (B-iv) A propylene-based resin composition for medical use is provided, which contains 0.005 to 0.3 parts by weight of an agent and is used after high-pressure steam sterilization.
(Bi) Propylene-ethylene copolymer (b-1) having an ethylene content of 0.1 to 3% by weight and MFR of 10 to 300 g / 10 min, an ethylene content of 5 to 20% by weight, and an MFR of 1 to 1 Propylene-ethylene block copolymer (B) composed of propylene-ethylene copolymer (b-2) at 50 g / 10 min
(B-ii) The weight ratio of the propylene-ethylene copolymer (b-1) to the propylene-ethylene copolymer (b-2) is 90:10 to 60:40.
(B-iii) Propylene-ethylene block copolymer (B) has an ethylene content of 2 to 8% by weight.
(B-iv) MFR ratio (b-1 / b-2) of propylene-ethylene copolymer (b-1) and propylene-ethylene copolymer (b-2) is 1 to 30, and propylene-ethylene The MFR of the block copolymer (B) is 10 to 100 g / 10 min.

  Further, according to the second invention of the present invention, in the first invention, the nucleating agent is 0.01 to 0.3 parts by weight of the nucleating agent (A) represented by the following formula (1): 2) selected from the group consisting of 0.01 to 0.2 parts by weight of the nucleating agent (B) and 0.005 to 0.03 parts by weight of the nucleating agent (C) represented by the following formula (3) A propylene-based resin composition for medical use is provided, which is at least one nucleating agent.

［式中、Ｒ^１は、直接結合、硫黄又は炭素数１〜９のアルキレン基又はアルキリデン基であり、Ｒ^２及びＲ^３は、同一又は異なって、それぞれ水素原子又は炭素数１〜８のアルキル基であり、ＭはＮａであり、ｎはＭの価数である。］

[Wherein, R ¹ is a direct bond, sulfur, an alkylene group having 1 to 9 carbon atoms or an alkylidene group, and R ² and R ³ are the same or different and each represents a hydrogen atom or an alkyl having 1 to 8 carbon atoms. A group, M is Na, and n is the valence of M. ]

［式中、Ｒ^１は、水素原子又は炭素数１〜４のアルキル基を示し、Ｒ^２及びＲ^３は、同一又は異なって、それぞれ水素原子又は炭素数１〜１２のアルキル基を示し、Ｍは、周期律表第ＩＩＩ族または第ＩＶ族の金属原子を示し、Ｘは、Ｍが周期律表第ＩＩＩ族の金属原子を示す場合には、ＨＯ−を示し、Ｍが周期律表第ＩＶ族の金属原子を示す場合には、Ｏ＝又は（ＨＯ）_２−を示す。］

[Wherein, R ¹ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, R ² and R ³ are the same or different and each represents a hydrogen atom or an alkyl group having 1 to 12 carbon atoms; Represents a group III or group IV metal atom of the periodic table, X represents HO— when M represents a group III metal atom of the periodic table, and M represents group IV of the periodic table. When a group metal atom is shown, O = or (HO) _2- . ]

［Ｒ_１〜Ｒ_３：ｔ−ブチル］

_[R 1 ~R 3: t- butyl]

  According to the third invention of the present invention, there is provided a medical propylene-based resin composition according to the first or second invention, wherein the sterilization method is high-pressure steam sterilization at 100 ° C to 130 ° C. The

  In addition, according to the fourth invention of the present invention, a medical molded article using the propylene-based resin composition of any one of the first to third inventions is provided.

According to the fifth invention of the present invention, there is provided a kit preparation characterized in that the medical molded article of the fourth invention is a kit preparation.
According to a sixth aspect of the present invention, there is provided a prefilled syringe characterized in that the kit preparation of the fifth aspect is a prefilled syringe.

  1. The medical propylene-based resin composition of the present invention is the 16th revision Japanese Pharmacopoeia 7.02 Plastic Drug Container Test Method Standards for plastic water injection containers 2.1 Polyethylene or polypropylene water injection containers (4) heavy metals, (5) lead, (6) cadmium, (7) ignition residue, (8) eluate It satisfies the test items and maintains excellent heat resistance, rigidity, impact resistance, injection moldability, and transparency.

FIG. 1 is a flow sheet of a continuous horizontal gas phase polymerization apparatus used in Examples.

The present invention is a propylene homopolymer polymerized by a Ziegler-Natta catalyst or a propylene-based copolymer composed of propylene and an α-olefin having a content of less than 1% by weight, and has an MFR of 0.5 to 100 g / 10. And propylene-ethylene block copolymer polymerized with a Ziegler-Natta catalyst satisfying the following characteristics (Bi) to (B-iv): It is characterized by containing 0.005-0.3 parts by weight of a nucleating agent for 100 parts by weight of a propylene-based resin composed of 1-40 parts by weight of the combined body (B), and being used after high-pressure steam sterilization. This is a propylene-based resin composition for medical use, and is useful for molded articles obtained from the composition, particularly kit preparations. Hereinafter, the components, the method for producing the composition, the molded product, and the like will be described in detail.
(Bi) Propylene-ethylene copolymer (b-1) having an ethylene content of 0.1 to 3% by weight and MFR of 10 to 300 g / 10 min, an ethylene content of 5 to 20% by weight, and an MFR of 1 to 1 Propylene-ethylene block copolymer (B) composed of propylene-ethylene copolymer (b-2) at 50 g / 10 min
(B-ii) The weight ratio of the propylene-ethylene copolymer (b-1) to the propylene-ethylene copolymer (b-2) is 90:10 to 60:40.
(B-iii) Propylene-ethylene block copolymer (B) has an ethylene content of 2 to 8% by weight.
(B-iv) MFR ratio (b-1 / b-2) of propylene-ethylene copolymer (b-1) and propylene-ethylene copolymer (b-2) is 1 to 30, and propylene-ethylene The MFR of the block copolymer (B) is 10 to 100 g / 10 min.

[1] Components of the composition Propylene-based resin (A) Propylene-based (co) polymer The (A) propylene-based (co) polymer used in the medical propylene-based resin composition of the present invention is a propylene homopolymer, a propylene content of 1 wt. It may be a propylene copolymer composed of less than% α-olefin or a mixture thereof.
(A) The propylene-based (co) polymer is preferably a homopolymer from the viewpoint of heat resistance during autoclave sterilization, and is preferably a random copolymer composed of propylene and an α-olefin from the viewpoint of transparency. 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. These propylene polymers may be used as a mixture of two or more. In addition, when the α-olefin content is 1% by weight or more, it becomes difficult to use from the viewpoint of heat resistance.
Specific examples of the propylene-based copolymer include propylene-ethylene copolymer, propylene-butene-1 copolymer, propylene-hexene-1 copolymer, propylene-octene-1 copolymer, propylene-ethylene. A binary combination of any amount of comonomers, such as a -butene-1 copolymer, a propylene-ethylene-hexene-1 copolymer, a propylene-butene-1-octene-1 copolymer, or the like A terpolymer can be exemplified.

In medical applications, sterilization is generally performed. Specifically, high-pressure steam sterilization, radiation sterilization, ethylene oxide gas (EOG) sterilization, ultraviolet sterilization, and the like are performed. In the present invention, high-pressure steam sterilization is assumed, and the ideal high-pressure steam sterilization is high-pressure steam sterilization called overkill at 121 ° C. for 20 minutes. When this treatment is performed, a propylene homopolymer Or a propylene-based copolymer composed of propylene and an α-olefin having a content of less than 1% by weight. When a random copolymer having a high ethylene content is used, there is a problem that it is deformed by high-pressure steam sterilization. In the case of high-pressure steam sterilization, transparency is more likely to deteriorate than that before sterilization, and those that are less likely to deteriorate are preferable.

The α-olefin content used in the propylene-based (co) polymer (A) is less than 1% by weight, preferably less than 0.5% by weight. If the α-olefin content is 1% by weight or more, the rigidity is lowered and there is a risk of deformation during autoclave sterilization.
Here, propylene and α-olefin are values measured by ¹³ C-NMR method under the following conditions.
Apparatus: JEOL-GSX270 manufactured by JEOL Ltd.
Concentration: 300 mg / 2 mL
Solvent: Orthodichlorobenzene

In the case where the propylene-based (co) polymer (A) used in the present invention is a propylene homopolymer, the isotactic pentad fraction is preferably 0.90 or more, more preferably 0.94 to 0.98. It is. It is preferable that the isotactic pentad fraction is 0.90 or more because rigidity and barrier properties are excellent.
Here, the isotactic pentad fraction is a value measured by a proton decoupling method using ¹³ C-NMR.

  The propylene-based (co) polymer (A) used in the present invention has an MFR in the range of 0.5 to 100 g / 10 minutes, preferably 1 to 50 g / 10 minutes, and 2 to 30 g / 10 minutes. Further preferred. If the melt flow rate (MFR) is less than 0.5 g / 10 minutes, there is a risk that molding processability is lowered and a satisfactory product cannot be obtained. Moreover, when it exceeds 100 g / 10 minutes, there exists a concern about the fall of mechanical strength.

  The production method of the propylene-based (co) polymer (A) is not particularly limited, but a polymerization method using a Ziegler-Natta catalyst as the stereoregular catalyst is preferable.

  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.

Propylene-based (co) polymer production methods include slurry methods using an inert solvent, solution methods, gas phase methods that do not substantially use a solvent, or bulk using a polymerization monomer as a solvent in the presence of the above catalyst. Examples thereof include a polymerization method.
For example, in the case of slurry polymerization, 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, and the molecular weight of the resulting propylene-based (co) 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.

(B) Propylene-ethylene block copolymer The weight ratio of the propylene-ethylene copolymer (b-1) and the propylene-ethylene copolymer (b-2) used in the present invention is in the range of 90:10 to 60:40. And preferably 87:13 to 65:35, more preferably 84:16 to 70:30. When the upper limit of the weight ratio of the propylene-ethylene copolymer (b-1) is 90 or less, the impact resistance of the molded article is improved, and when the lower limit is 60 or more, the solidification at the time of molding is accelerated and the moldability is improved. improves.
The MFR of the propylene-ethylene block copolymer (B) is preferably in the range of 10 to 100 g / 10 min, more preferably 25 to 50 g / 10 min.

When the MFR is 10 g / 10 min or more, molding processability is improved due to improved fluidity, and when it is 100 g / 10 min or less, impact resistance is improved. The MFR ratio (b-1 / b-2) of the propylene-ethylene copolymer (b-1) and the propylene-ethylene copolymer (b-2) is preferably in the range of 1 to 30, more Preferably it is 3.5-30, More preferably, it is 5-30, Most preferably, it is 8-30. When it is above the lower limit of this range, the impact resistance is improved, and when it is below the upper limit, the dispersibility of the propylene-ethylene copolymer (b-2) with respect to the propylene-ethylene copolymer (b-1) becomes good. Transparency is improved. In addition, a method for adjusting MFR by CR (control rheology) using a molecular weight modifier is generally known. However, in the present invention, it is possible to adjust MFR only by polymerization conditions without CR. From the viewpoint of preventing resin burn at the time.
The ethylene content of the propylene-ethylene block copolymer (B) needs to be in the range of 2-8 wt%, preferably 3-7 wt%, more preferably 3-6 wt%, most preferably 4 ~ 6% by weight.
When it is at least the lower limit of this range, the transparency and impact resistance of the molded product are improved. If it is less than or equal to the upper limit, stickiness is reduced due to a decrease in the low crystalline component, and drug adsorption is improved.

The propylene-ethylene copolymer (b-1) used in the present invention satisfies the following characteristics.
Characteristic 1: MFR
The MFR of the propylene-ethylene copolymer (b-1) used in the present invention needs to be in the range of 10 to 300 g / 10 min, preferably 30 to 200 g / 10 min, more preferably 50 to 150 g / 10 min. is there. If it is above the lower limit of this range, the moldability is improved due to the improvement of fluidity, and even when the molded product is molded with a thickness of 2.5 mm or less, the molding orientation is difficult to be applied and impact is applied. In this case, cracks in the molding orientation direction can be prevented, and those having an upper limit value or less are preferable in terms of economy because the productivity of the resin composition is good, and the impact resistance of the molded product is excellent.
The method for controlling the MFR value is well known, and can be easily adjusted by adjusting the temperature and pressure, which are polymerization conditions, or by controlling the amount of hydrogen added during the polymerization of a chain transfer agent such as hydrogen.

Characteristic 2: Ethylene content The ethylene content of the propylene-ethylene copolymer (b-1) used in the present invention needs to be in the range of 0.1 to 3% by weight, preferably 1.0 to 2.8. % By weight, more preferably 1.5 to 2.6% by weight. When it is at least the lower limit of this range, the transparency of the molded article becomes good and the impact resistance after high-pressure steam sterilization is excellent. On the other hand, if it is less than or equal to the upper limit, the crystallization temperature rises and the solidification at the time of molding becomes faster and the molding processability becomes good.
The ethylene content can be adjusted by controlling the monomer composition of propylene and ethylene during polymerization.

The propylene-ethylene copolymer (b-2) used in the present invention satisfies the following characteristics.
Characteristic 1: MFR
The MFR of the propylene-ethylene copolymer (b-2) used in the present invention needs to be in the range of 1 to 50 g / 10 min, preferably 1 to 30 g / 10 min, more preferably 1 to 15 g / 10 min. Most preferably, it is 1-10 g / 10min.
If it is at least the lower limit of this range, the dispersibility in the propylene-ethylene copolymer (A) is improved, and it becomes possible to suppress the generation of fish eyes in the molded product. When the amount is not more than the upper limit, the low crystal component is less likely to bleed on the surface, so that the drug adsorption is good and the impact resistance after high-pressure steam sterilization is good. In addition, a method for adjusting MFR by CR (control rheology) using a molecular weight modifier is generally known. However, in the present invention, it is possible to adjust MFR only by polymerization conditions without CR. From the viewpoint of preventing resin burn at the time.

Characteristic 2: Ethylene content The ethylene content of the propylene-ethylene copolymer (b-2) used in the present invention needs to be in the range of 5 to 20 wt%, preferably 7 to 15 wt%, more preferably 8 to 13% by weight. When it is at least the lower limit of this range, the impact resistance of the molded product is improved. Moreover, while being compatible with a propylene-ethylene copolymer (b-1) as it is below an upper limit, transparency of a molded article becomes favorable, and a propylene-ethylene copolymer (b-2) becomes. By making it difficult to bleed on the surface of the molded article, stickiness and drug adsorption are improved.

Further, the propylene-ethylene block copolymer (B) preferably has a −15 ° C. soluble content by temperature-temperature elution fractionation (TREF), preferably 10% by weight or less, in order to reduce stickiness and drug adsorption. Is 9% by weight or less, more preferably 8% by weight or less, particularly preferably 7% by weight or less, and most preferably 6% by weight or less. If this soluble content is within this range, the adverse effects on product quality due to stickiness and bleed-out can be suppressed, and powder particles do not flow poorly due to particle aggregation and reactor adhesion during polymer production. A polymer can be produced stably.
In the propylene-ethylene block copolymer (B), the TREF measurement method is specifically performed as follows. A sample is dissolved in o-dichlorobenzene (containing 0.5 mg / ml BHT (2,6-di-t-butyl-p-cresol)) at 140 ° C. to obtain a solution. After this is introduced into a TREF column at 140 ° C., it is cooled to 100 ° C. at a temperature decreasing rate of 8 ° C./min, subsequently cooled to −15 ° C. at a temperature decreasing rate of 4 ° C./min, and held for 60 minutes. Thereafter, -15 ° C o-dichlorobenzene (containing 0.5 mg / ml BHT), which is a solvent, flows through the column at a flow rate of 1 ml / min, and is dissolved in -15 ° C o-dichlorobenzene in the TREF column. The components are eluted for 10 minutes, and then the column is linearly heated to 140 ° C. at a rate of temperature increase of 100 ° C./hour to obtain an elution curve. The TREF evaluation method is well known to those skilled in the art. For example, detailed measurement methods are described in the following documents.
G. Glockner, J. et al. Appl. Polym. Sci. : Appl. Polym. Symp. 45, 1-24 (1990)
L. Wild, Adv. Polym. Sci. 98, 1-47 (1990)
J. et al. B. P. Soares, A .; E. Hamielec, Polymer; 36, 8, 1639-1654 (1995)

In addition, the ratio of the propylene-ethylene copolymers (b-1) and (b-2) in the propylene-ethylene resin composition (B) is obtained from the material balance at the time of polymerization when manufactured by continuous polymerization. In the case of manufacturing by blending, it is a value obtained from each prescription ratio.
Each ethylene content is a value obtained by measurement by ¹³ C-NMR method.

As a catalyst used for obtaining the propylene-ethylene copolymer (b-1) and the propylene-ethylene copolymer (b-2) used in the present invention, a so-called Ziegler in which a titanium compound and an organic aluminum are combined.・ Natta catalyst can be used.
In the present invention, a propylene-based resin composition for medical use that is excellent in injection molding processability and has a good balance of rigidity and impact resistance and transparency after high-pressure steam sterilization is particularly preferable. For this reason, a Ziegler-Natta catalyst having a broad molecular weight distribution and high stereoregularity is generally preferable to a metallocene catalyst. When the propylene-ethylene copolymer (b-1) and the propylene-ethylene copolymer (b-2) are obtained with a Ziegler-Natta catalyst, the molecular weight distribution is generally wider than that obtained with a metallocene catalyst. As a result, the fluidity in the mold is increased, the injection molding processability is improved, and the composition distribution is widened, so that the propylene-ethylene copolymer (b-1) and the propylene-ethylene copolymer (b- The compatibility of 2) is increased and the impact resistance is improved.
Specifically, regarding stereoregularity, 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 balance between rigidity and impact resistance is good. Here, the isotactic pentad fraction (mmmm) is a value measured by ¹³ C-NMR method.

  Regarding the molecular weight distribution, the value of (weight average molecular weight) / (number average molecular weight), which is an index of the width of the molecular weight distribution, is preferably 2.0 to 8.0, more preferably 2.5 to 7.0, and further Preferably it is 3.0-6.0. When it is at least the lower limit, the resin fluidity during injection molding is excellent. On the other hand, if it is less than or equal to the upper limit, molding orientation is difficult to be applied, and cracking along the molding orientation hardly occurs, and impact resistance after high-pressure steam sterilization is good. Here, the weight average molecular weight and the number average molecular weight are values measured by a gel permeation chromatography (GPC) method described later.

Regarding the production process of the propylene-ethylene copolymer (b-1) and the propylene-ethylene copolymer (b-2), any process may be used as long as the above-mentioned characteristics are satisfied. The mixture of the copolymer (b-1) and the propylene-ethylene copolymer (b-2) may be produced by any method as long as the above properties are satisfied. In particular, it is preferable to produce a mixture of propylene-ethylene copolymer (b-1) and propylene-ethylene copolymer (b-2) by a two-stage continuous gas phase polymerization method using a horizontal reactor. The reason is that when a mixture of propylene-ethylene copolymer (b-1) and propylene-ethylene copolymer (b-2) is produced by a two-stage continuous polymerization method, it is produced by a bulk or slurry batch polymerization method. This method is costly because the yield of the polymer per unit time and per unit polymerization vessel is lower than that in the gas phase continuous polymerization method. On the other hand, in the two-stage continuous gas phase polymerization method using a gas phase vertical reactor, distribution occurs in the residence time of each catalyst particle in the polymerizer of each stage, so that propylene-ethylene copolymer (b-1) and propylene are produced. -It becomes an aggregate | assembly of the polymer particle | grains which have distribution in the content rate of ethylene copolymer (b-2), and the fault of the quality surface derived from the nonuniformity of this distribution may generate | occur | produce. Further, when the polymerization process of the propylene-ethylene copolymer (b-2) containing a relatively large amount of ethylene in the second stage is carried out by gas phase polymerization using a gas medium, the polymerization amount increases as the polymerization amount in the second stage increases. The adhesiveness of the coalesced particles may increase, and stable operation may be difficult. In addition, when the polymerization heat is not sufficiently cooled, adhesion to the polymerization vessel wall, the stirring blades, or the like may occur. One way to prevent stickiness is to reduce the amount of catalyst that enters the second stage polymerization reactor while the residence time is short. In some cases, such defects as increase in operation and complexity of operation may occur. Therefore, regarding the production process of the mixture of propylene-ethylene copolymer (b-1) and propylene-ethylene copolymer (b-2), the heat of polymerization is removed by using the latent heat of vaporization of liquefied propylene. Rotating around a horizontal axis that makes it possible to produce a high quality propylene-ethylene copolymer (b-1) and a mixture of propylene-ethylene copolymer (b-2) with a narrow residence time distribution Most preferably, it is produced in a two-stage continuous gas phase polymerization process having a horizontal reactor with a stirrer.
When a mixture of propylene-ethylene copolymer (b-1) and propylene-ethylene copolymer (b-2) is produced by the two-stage continuous gas phase polymerization process having the above horizontal reactor, the first stage After the propylene-ethylene copolymer (b-1) is polymerized with the same catalyst particles, the propylene-ethylene copolymer (b-2) is polymerized in the second stage with the same catalyst particles. The copolymer (b-1) and the propylene-ethylene copolymer (b-2) coexist. In that case, the dispersibility of the propylene-ethylene copolymer (b-2) with respect to the propylene-ethylene copolymer (b-1) becomes the best, and when the powder particles are pelletized into a molded product, they are produced separately. The propylene-ethylene copolymer (b-1) pellets and the propylene-ethylene copolymer (b-2) pellets were melt-kneaded with an extruder and then compared with the molded ones in comparison with the molded ones. Since the compatibility between (b-1) and the propylene-ethylene copolymer (b-2) is remarkably good, it is possible to obtain a high-quality molded product resulting from the uniformity of physical properties in the molded product, The thing which is excellent in transparency and excellent in impact resistance can be obtained.

  The propylene-based (co) polymer (A) is preferably 60 to 99 parts by weight, and the propylene-ethylene block copolymer (B) is preferably in the range of 1 to 40 parts by weight. Further, the propylene-based (co) polymer (A) is The propylene-ethylene block copolymer (B) in the range of 60 to 90 parts by weight is preferably in the range of 10 to 40 parts by weight, and most preferably the propylene-based (co) polymer (A) is 65 to 85 parts by weight of propylene- The ethylene block copolymer (B) is in the range of 15 to 35 parts by weight. Within this range, the balance of rigidity, impact resistance, heat resistance, and transparency after high-pressure steam sterilization is excellent.

2. Nucleating agent The blending amount of the nucleating agent used in the medical propylene-based resin composition of the present invention is 0.005 to 0.3 parts by weight with respect to 100 parts by weight of the propylene-based resin (A) + (B). It is used in the range. If it is 0.005 parts by weight or more, transparency is sufficiently exhibited, and if it is 0.3 parts by weight or less, the 16th revision Japanese Pharmacopoeia 7.02 Plastic Drug Container Test Method Specification of plastic water-based injection container 2.1 Not only may the test of polyethylene or polypropylene water-based injection container pass, but it is advantageous from the viewpoint of cost-effectiveness (cost performance).
As such a nucleating agent, the nucleating agents (A) to (C) shown below are desirable.
The nucleating agent (A) used selectively is an organophosphate metal salt compound represented by the formula (1).

［式（１）中、Ｒ^１は、直接結合、硫黄又は炭素数１〜９のアルキレン基又はアルキリデン基であり、Ｒ^２及びＲ^３は、水素原子又は炭素数１〜８のアルキル基であり、ＭはＮａであり、ｎはＭの価数である。］

In Expression (1), ^{R 1} represents a direct bond, a sulfur or an alkylene group or alkylidene group having 1 to 9 carbon atoms, ^{R 2} and ^{R 3} is a hydrogen atom or an alkyl group having 1 to 8 carbon atoms , M is Na, and n is the valence of M. ]

Specific examples of the organophosphate metal salt compound represented by the formula (1) include sodium-2,2′-methylene-bis- (4,6-di-t-butylphenyl) phosphate, sodium-2, 2′-ethylidene-bis- (4,6-di-t-butylphenyl) phosphate, sodium-2,2′-ethylidene-bis- (4-i-propyl-6-t-butylphenyl) phosphate, Sodium-2,2′-butylidene-bis- (4,6-dimethylphenyl) phosphate, sodium-2,2′-butylidene-bis- (4,6-di-t-butylphenyl) phosphate, sodium 2,2′-t-octylmethylene-bis- (4,6-methylphenyl) phosphate, sodium-2,2′-t-octylmethylene-bis- (4,6-di-t-butyl Phenyl) phosphate, sodium-2,2′-methylene-bis- (4-methyl-6-tert-butylphenyl) phosphate, sodium-2,2′-methylene-bis- (4-ethyl-6-t) -Butylphenyl) phosphate, sodium (4,4'-dimethyl-6,6'-di-t-butyl-2,2'-biphenyl) phosphate, sodium-2,2'-ethylidene-bis- (4 -S-butyl-6-tert-butylphenyl) phosphate, sodium-2,2'-methylene-bis- (4,6-di-methylphenyl) phosphate, sodium-2,2'-methylene-bis- Examples thereof include (4,6-di-ethylphenyl) phosphate and a mixture of two or more thereof. Of these, sodium-2,2′-methylene-bis- (4,6-di-t-butylphenyl) phosphate is particularly preferable.
A commercially available product can be used as such a nucleating agent. Specifically, NA-11 manufactured by ADEKA Corporation can be mentioned.

  The blending amount of the nucleating agent (A) used selectively is 0.01 to 0.00 with respect to 100 parts by weight of the propylene-based (co) polymer (A) + propylene-ethylene block copolymer (B). The range of 3 parts by weight is preferable, and the range of 0.01 to 0.2 parts by weight is more preferable. If it is 0.01 part by weight or more, a sufficient effect is obtained, and the range of 0.3 part by weight or less is advantageous from the viewpoint of cost effectiveness (cost / performance).

  The nucleating agent (B) used selectively is an aromatic phosphate ester represented by the formula (2).

［式（２）中、Ｒ^１は、水素原子又は炭素数１〜４のアルキル基を示し、Ｒ^２及びＲ^３は、水素原子又は炭素数１〜１２のアルキル基を示し、Ｍは、周期律表第ＩＩＩ族または第ＩＶ族の金属原子を示し、Ｘは、Ｍが周期律表第ＩＩＩ族の金属原子を示す場合には、ＨＯ−を示し、Ｍが周期律表第ＩＶ族の金属原子を示す場合には、Ｏ＝又は（ＨＯ）_２−を示す。］

[In Formula (2), R ¹ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, R ² and R ³ represent a hydrogen atom or an alkyl group having 1 to 12 carbon atoms, and M represents a period. Represents a Group III or Group IV metal atom, X represents HO— when M represents a Group III metal atom, and M represents a Group IV metal of the Periodic Table When showing an atom, it shows O = or (HO) _2- . ]

  Specific examples of the aromatic phosphates represented by the formula (2) include, for example, hydroxyaluminum-bis [2,2′-methylene-bis (4,6-dimethylphenyl) phosphate], hydroxyaluminum-bis. [2,2′-ethylidene-bis (4,6-dimethylphenyl) phosphate], hydroxyaluminum-bis [2,2′-methylene-bis (4,6-diethylphenyl) phosphate], hydroxyaluminum-bis [2,2′-ethylidene-bis (4,6-diethylphenyl) phosphate], hydroxyaluminum-bis [2,2′-methylene-bis (4,6-di-t-butylphenyl) phosphate], And hydroxyaluminum-bis [2,2′-ethylidene-bis (4,6-di-tert-butylpheny ) Phosphate], hydroxyaluminum-bis [2,2′-methylene-bis (4-methyl-6-tert-butylphenyl) phosphate], hydroxyaluminum-bis [2,2′-ethylidene-bis (4- Methyl-6-tert-butylphenyl) phosphate], hydroxyaluminum-bis [2,2′-methylene-bis (4-ethyl-6-tert-butylphenyl) phosphate], hydroxyaluminum-bis [2,2 '-Ethylidene-bis (4-ethyl-6-t-butylphenyl) phosphate], hydroxyaluminum-bis [2,2'-methylene-bis (4-i-propyl-6-t-butylphenyl) phosphate] ], Hydroxyaluminum-bis [2,2'-ethylidene-bis (4-i-propyl-6-t- Tilphenyl) phosphate] and the like, preferably hydroxyaluminum-bis [2,2′-methylene-bis (4,6-di-t-butylphenyl) phosphate], and hydroxyaluminum-bis [2, 2′-ethylidene-bis (4,6-di-t-butylphenyl) phosphate], and a mixture of two or more of these.

It is effective to use the aromatic phosphates represented by the formula (2) together with an organic alkali metal salt.
The organic alkali metal salt may be at least one organic alkali metal salt selected from the group consisting of alkali metal carboxylates, alkali metal β-diketonates and alkali metal β-ketoacetate salts.
Examples of the alkali metal constituting the organic alkali metal salt include lithium, sodium, and potassium.
Examples of the carboxylic acid constituting the alkali metal carboxylate include acetic acid, propionic acid, acrylic acid, octylic acid, isooctylic acid, nonanoic acid, decanoic acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, Ricinoleic acid, 12-hydroxystearic acid, behenic acid, montanic acid, melicic acid, β-dodecylmercaptoacetic acid, β-dodecylmercaptopropionic acid, β-N-laurylaminopropionic acid, β-N-methyl-lauroylaminopropionic acid Aliphatic monocarboxylic acids such as malonic acid, succinic acid, adipic acid, maleic acid, azelaic acid, sebacic acid, dodecanedioic acid, citric acid, butanetricarboxylic acid, butanetetracarboxylic acid and other polyvalent aliphatic carboxylic acids such as naphthene Acid, cyclopentanecarboxylic acid, 1-methyl Cyclopentanecarboxylic acid, 2-methylcyclopentanecarboxylic acid, cyclopentenecarboxylic acid, cyclohexanecarboxylic acid, 1-methylcyclohexanecarboxylic acid, 4-methylcyclohexanecarboxylic acid, 3,5-dimethylcyclohexanecarboxylic acid, 4-butylcyclohexanecarboxylic acid , Cyclooctenecyclohexanecarboxylic acid, cyclohexenecarboxylic acid, cycloaliphatic mono- or polycarboxylic acid such as 4-cyclohexene-1,2-dicarboxylic acid, benzoic acid, toluic acid, xylyl acid, ethylbenzoic acid, 4-t- Aromatic mono- or polycarboxylic acids such as butylbenzoic acid, salicylic acid, phthalic acid, trimellitic acid, pyromellitic acid and the like can be mentioned.
Examples of the β-diketone compound constituting the alkali metal β-diketonate include acetylacetone, pivaloylacetone, palmitoylacetone, benzoylacetone, pivaloylbenzoylacetone, and dibenzoylmethane.
Examples of the β-ketoacetate constituting the alkali metal β-ketoacetate include ethyl acetoacetate, octyl acetoacetate, lauryl acetoacetate, stearyl acetoacetate, ethyl benzoyl acetate, benzoyl acetate lauryl and the like. It is done.
The alkali metal carboxylate, alkali metal β-diketonate, or alkali metal β-ketoacetate salt, which is a component of the organic alkali metal salt, includes the above alkali metal and carboxylic acid, β-diketone compound, or β-ketoacetate, respectively. And can be produced by a conventionally known method. Among these alkali metal salt compounds, alkali metal aliphatic monocarboxylates, particularly lithium aliphatic carboxylates are preferable, and aliphatic monocarboxylates having 8 to 20 carbon atoms are particularly preferable.
A commercially available product can be used as such a nucleating agent. Specific examples include NA-21 manufactured by ADEKA Corporation.

  The blending amount of the nucleating agent (B) used selectively is 0.01 to 0.00 with respect to 100 parts by weight of the propylene-based (co) polymer (A) + propylene-ethylene block copolymer (B). The range of 20 parts by weight is preferable, and the range of 0.05 to 0.15 parts by weight is more preferable. If it is 0.01 part by weight or more, a sufficient effect is obtained, and the range of 0.20 part by weight or less is advantageous from the viewpoint of cost effectiveness (cost / performance).

  The nucleating agent (C) used selectively is a nucleating agent represented by the formula (3).

［Ｒ_１〜Ｒ_３：ｔ−ブチル］
この様な造核剤としては、市販のものを用いることができる。具体的には、ＢＡＳＦ社製 ＸＴ３８６を挙げることができる。
選択的に用いられる造核剤（Ｃ）の配合量は、プロピレン系（共）重合体（Ａ）＋プロピレン−エチレンブロック共重合体（Ｂ）の１００重量部に対し、０．００５〜０．０３重量部の範囲が好ましく、０．０１〜０．０２重量部の範囲がより好ましい。０．００５重量部以上であれば十分な効果が得られ、０．０３重量部以下である範囲は、費用対効果（コスト・パフォーマンス）の点から有利である。

_[R 1 ~R 3: t- butyl]
A commercially available product can be used as such a nucleating agent. Specific examples include XT386 manufactured by BASF.
The blending amount of the nucleating agent (C) used selectively is 0.005 to 0.005 based on 100 parts by weight of the propylene-based (co) polymer (A) + propylene-ethylene block copolymer (B). The range of 03 parts by weight is preferable, and the range of 0.01 to 0.02 parts by weight is more preferable. If it is 0.005 parts by weight or more, a sufficient effect is obtained, and the range of 0.03 parts by weight or less is advantageous from the viewpoint of cost effectiveness (cost / performance).

  In addition to the nucleating agents (A) to (C), the medical propylene-based resin composition of the present invention includes other nucleating agents such as sorbitol nucleating agents, nonitol nucleating agents and talc. A nucleating agent can be added as long as the effect of the present invention is not significantly impaired.

3. Neutralizer In the medical propylene-based resin composition of the present invention, it is desirable to add a neutralizer. Specific examples of the neutralizing agent include metal fatty acid salts such as calcium stearate, zinc stearate, and magnesium stearate, hydrotalcite (trade name: DHT-4A, manufactured by Kyowa Chemical Industry Co., Ltd., the following general formula (4) Magnesium aluminum composite hydroxide salt represented by the formula (1), Mizukarak (trade name, lithium aluminum composite hydroxide salt represented by the following general formula (5) manufactured by Mizusawa Chemical Industry Co., Ltd.), and the like. In particular, when used as a member that is in contact with the liquid for a long period of time, such as a prefilled syringe, a kit preparation, or an infusion bag, hydrotalcite or mizucarac that does not elute into the liquid that comes into contact is advantageous.

Mg _1-x Al _x (OH) ₂ (CO ₃ ) _{x / 2} · mH ₂ O (4)
[Wherein x is 0 <x ≦ 0.5, and m is a number of 3 or less. ]

[Al ₂ Li (OH) ₆ ] _n X · mH ₂ O (5)
[Wherein, X is an inorganic or organic anion, n is the valence of the anion (X), and m is 3 or less. ]

  The blending amount of the neutralizing agent selectively used in the medical propylene-based resin composition of the present invention is 0.005 to 0.2 weight with respect to 100 parts by weight of the propylene-based polymer (A) + (B). The range of parts is preferable, and the range of 0.01 to 0.05 parts by weight is more preferable.

4). Lubricant In the medical propylene-based resin composition of the present invention, a lubricant can be blended. Examples of the lubricant include known lubricants, but butyl stearate and silicone oil are preferable, and silicone oil is particularly preferable.
Specific silicone oils include dimethylpolysiloxane, methylphenylpolysiloxane, methylhydrodienepolysiloxane, α-ωbis (3-hydroxypropyl) polydimethylsiloxane, polyoxyalkylene (C ₂ -C ₄ ) dimethylpolysiloxane. And a polyorgano (C ₁ -C ₂ alkyl group and / or phenyl group) siloxane and polyalkylene (C ₂ -C ₃ ) glycol condensate. Of these, dimethylpolysiloxane and methylphenylpolysiloxane are preferred. These lubricants may be used alone or in combination.
When silicone such as dimethylpolysiloxane is added, not only can scratches that occur during molding be prevented, but also burns that can occur in cylinders and hot runners can be prevented.

  The blending amount of the lubricant selectively used in the medical propylene-based resin composition of the present invention is 0.001 to 0.5 parts by weight with respect to 100 parts by weight of the propylene-based polymer (A) + (B). Preferably, 0.01-0.15 weight part is more preferable, and 0.03-0.1 weight part is especially preferable. If it is 0.001 part by weight or more, a sufficient effect can be expected, and the range of 0.5 part by weight or less is advantageous from the viewpoint of cost effectiveness (cost / performance).

5. Other Additives In the medical propylene resin composition of the present invention, in addition to the components described above, various antioxidants, ultraviolet absorbers, light stabilizers and the like used as stabilizers for propylene polymers, etc. Additives can be blended.

  Specifically, as the antioxidant, bis (2,6-di-t-butyl-4-methylphenyl) pentaerythritol-di-phosphite, di-stearyl-pentaerythritol-di-phosphite, bis ( 2,4-di-t-butylphenyl) pentaerythritol-diphosphite, tris (2,4-di-t-butylphenyl) phosphite, tetrakis (2,4-di-t-butylphenyl) -4 Phosphorous antioxidants such as 4,4'-biphenylene-diphosphonite, tetrakis (2,4-di-t-butyl-5-methylphenyl) -4,4'-biphenylene-diphosphonite, 2,6-di-t-butyl-p-cresol, tetrakis [methylene (3,5-di-t-butyl-4-hydroxyhydrocinnamate)] methane, 1 3,5-trimethyl-2,4,6-tris (3,5-di-tert-butyl-4-hydroxybenzyl) benzene, tris (3,5-di-tert-butyl-4-hydroxybenzyl) isocyanurate Phenolic antioxidants such as di-stearyl-ββ'-thio-di-propionate, di-myristyl-ββ'-thio-di-propionate, di-lauryl-ββ'-thio-di-propionate An antioxidant etc. are mentioned.

  Examples of the ultraviolet absorber include 2-hydroxy-4-n-octoxybenzophenone, 2- (2′-hydroxy-3 ′, 5′-di-t-butylphenyl) -5-chlorobenzotriazole, 2- (2 And ultraviolet absorbers such as' -hydroxy-3'-t-butyl-5'-methylphenyl) -5-chlorobenzotriazole.

  Examples of the light stabilizer include n-hexadecyl-3,5-di-t-butyl-4-hydroxybenzoate, 2,4-di-t-butylphenyl-3 ′, 5′-di-t-butyl-4 ′. -Hydroxybenzoate, bis (2,2,6,6-tetramethyl-4-piperidyl) sebacate, dimethyl-2- (4-hydroxy-2,2,6,6-tetramethyl-1-piperidyl) succinate ) Ethanol condensate, 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- ( , Mention may be made of a light stabilizer such as 2,2,6,6-pentamethyl-4-piperidyl) amino] -6-chloro-1,3,5-triazine condensate.

  Further, amine-based antioxidants represented by the following general formula (6) and the following general formula (7), which have no discoloration and are excellent in resistance to NOx gas discoloration by radiation treatment, 5,7-di-t-butyl-3 Examples include lactone antioxidants such as-(3,4-di-methyl-phenyl) -3H-benzofuran-2-one, and vitamin E antioxidants such as the following general formula (8).

  In addition, an antistatic agent, a slip agent, a dispersant such as a fatty acid metal salt, a dye, a pigment, polyethylene, an olefin-based elastomer, and the like can be blended within a range that does not impair the object of the present invention.

[2] Method for Producing Medical Propylene Resin Composition The medical propylene resin composition of the present invention comprises (A) + (B) propylene polymer and nucleating agent, preferably selectively used. After mixing at least one mixture of the nucleating agents (A) to (C) and, if necessary, other additives into a Henschel mixer (trade name), a super mixer, a ribbon blender, etc., It can be obtained by melt-kneading in a temperature range of 190 to 260 ° C. with an ordinary single-screw extruder, twin-screw extruder, Banbury mixer, plastic bender, roll or the like.

[3] Medical molded product The medical molded product of the present invention is obtained by molding the above-mentioned medical propylene-based resin composition by various molding methods such as injection molding, extrusion molding, and blow molding, which are known methods. However, an injection molding method with high dimensional accuracy and easy to make a complicated shape is desirable.
Moreover, the medical molded article of the present invention is useful as a kit preparation, suitable for a syringe barrel and a storage container filled with a drug solution, and particularly suitable for a prefilled syringe. 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 kind of liquid and a double chamber type that is filled with two kinds 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. An example of the single chamber type internal solution is a heparin solution.
The medical molded article of the present invention is sterilized by high-pressure steam, and is generally based on treatment at 121 ° C. for 20 minutes called overkill, preferably 80 ° C. to 140 ° C., more preferably The temperature may be from 100 ° C. to 140 ° C., and the time may be from several minutes to several hours, but it is preferably 1 minute to 10 hours, more preferably 5 minutes to 3 hours. The present invention is effective for high-pressure steam sterilization (autoclave sterilization).

  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 methods, and the following were used as propylene-based polymers, nucleating agents, and other additives (neutralizing agents, lubricants).

(1) Calculation of ethylene content
^The ethylene content was calculated from the measured value measured by ¹³ C-NMR method.

(2) MFR: Measured according to JIS K7210 at a heating temperature of 230 ° C. and a load of 21.2 N.

(3) Haze value: The value before sterilization was measured based on JIS K7136 using a sheet piece having a thickness of 1 mm. In addition, autoclave sterilization (AC sterilization, high-pressure steam sterilization) was performed at 121 ° C. for 20 minutes using a retort high-pressure steam sterilization / cooling device RKZ-30L manufactured by Alp Co., Ltd. The value measured according to K7136 was taken as the value after sterilization.

(4) 16th Amendment Japanese Pharmacopoeia Test: 7.02 Transparency, Heavy Metal, Lead, Cadmium, Strong in accordance with the test method of 2.1 Plastic Plastic Container Test Method 2.1 Polyethylene or Polypropylene Water Injection Container Thermal residue, foaming, pH, potassium permanganate reducing substance, ultraviolet absorption spectrum, and evaporation residue were measured. However, the sample was prepared by weighing a pellet with a weight equivalent to a surface area of 1200 cm ² on a 0.5 mm thick sheet and pressing it at 220 ° C. to obtain a sheet piece having a length of about 5 cm and a width of about 0.5 cm. After chopping it into pieces, it was washed with distilled water and then dried at room temperature. Put this in a hard glass container with an internal volume of about 300 ml, add exactly 200 ml of distilled water, seal with an appropriate stopper, heat at 121 ° C for 1 hour using a high-pressure steam sterilizer, and then reach room temperature. This solution was left as a test solution, and a blank test solution was prepared in the same manner using distilled water.

(5) Flexural modulus: Measured at 23 ° C. in accordance with JIS K7203 “Bending test method of hard plastic”.

(6) Charpy impact strength: measured at 23 ° C. according to JIS K7111.

(7) Deflection temperature under load (0.45 MPa): Measured according to JIS K7191.

2. Materials used (1) Propylene-based (co) polymer (A)
Propylene homopolymer (HPP1): Novatec MA3Q (trade name, manufactured by Nippon Polypro Co., Ltd.), catalyst: Ziegler catalyst, MFR: 10 g / 10 min, isotactic pentad fraction 0.96 (by ¹³ C-NMR Measurement).

(2) Propylene-ethylene block copolymer (B)
<Production Example 1 (PP-1)>
(I) Production of solid catalyst component (A) A 10 L autoclave equipped with a stirrer was sufficiently substituted with nitrogen, and 2 L of purified toluene was introduced. To this, 200 g of Mg (OEt) ₂ and 1 L of TiCl ₄ were added at room temperature. The temperature was raised to 90 ° C. and 50 ml of di-n-butyl phthalate was introduced. Thereafter, the temperature was raised to 110 ° C. to carry out a reaction for 3 hours. The reaction product was thoroughly washed with purified toluene. Subsequently, the refined toluene was introduce | transduced and the whole liquid quantity was adjusted to 2L. 1 L of TiCl ₄ was added at room temperature, the temperature was raised to 110 ° C., and the reaction was performed for 2 hours. The reaction product was thoroughly washed with purified toluene. Subsequently, the refined toluene was introduce | transduced and the whole liquid quantity was adjusted to 2L. 1 L of TiCl ₄ was added at room temperature, the temperature was raised to 110 ° C., and the reaction was performed for 2 hours. The reaction product was thoroughly washed with purified toluene. Furthermore, using purified n-heptane, toluene was replaced with n-heptane to obtain a solid component slurry. When a part of this slurry was sampled and analyzed, the Ti content of the solid component was 2.7% by weight.
Next, a 20 L autoclave equipped with a stirrer was sufficiently replaced with nitrogen, and 100 g of the solid component slurry was introduced as a solid component. Purified n-heptane was introduced to adjust the solid component concentration to 25 g / L. 50 ml of SiCl ₄ was added and a reaction was performed at 90 ° C. for 1 hr. The reaction product was thoroughly washed with purified n-heptane.
Thereafter, purified n-heptane was introduced to adjust the liquid level to 4 L. To this, 30 ml of dimethyldivinylsilane, 30 ml of (i-Pr) ₂ Si (OMe) ₂ and 80 g of Et ₃ Al in an n-heptane diluted solution were added as Et ₃ Al, and a reaction was carried out at 40 ° C. for 2 hours. The reaction product was thoroughly washed with purified n-heptane, and a part of the resulting slurry was sampled, dried and analyzed. As a result, the solid component was 1.2% by weight of Ti, (i-Pr) ₂ Si (OMe) ₂ was contained in an amount of 8.8% by weight.
Furthermore, prepolymerization was performed by the following procedure using the solid component obtained above. Purified n-heptane was introduced into the slurry, and the solid component concentration was adjusted to 20 g / L. Next, after cooling to 10 ° C. The slurry, 10 g was added n- heptane dilution of _Et 3 Al as _Et 3 Al, were fed over 4hr of propylene 280 g. After the supply of propylene was completed, the reaction was further continued for 30 minutes. Next, the gas phase was sufficiently replaced with nitrogen, and the reaction product was thoroughly washed with purified n-heptane. The obtained slurry was extracted from the autoclave and vacuum dried to obtain a solid catalyst component (A). This solid catalyst component contained 2.5 g of polypropylene per gram of solid component. Further, the portion of the solid catalyst component (A) excluding polypropylene contained 1.0% by weight of Ti and 8.2% by weight of (i-Pr) ₂ Si (OMe) ₂ .
(Ii) Manufacture of propylene-type polymer It demonstrates with the flow sheet shown in attached FIG. A gas phase polymerization reactor using two polymerization tanks was used. The two polymerization vessels 17 and 26 are continuous horizontal gas phase polymerization vessels (length / diameter = 5.2) equipped with a stirrer having an inner diameter D of 2100 mm, a length L of 11000 mm, and an internal volume of 40 m ^3. .
After replacing the inside of the polymerization vessel 17, a polypropylene powder from which polymer particles having a particle size of 500 μm or less were removed was charged, 120 g / Hr as the solid catalyst component (A), and a 15 wt% hexane solution of triethylaluminum in Ti in the catalyst component A It supplied continuously so that molar ratio might be set to 350 with respect to 1 mol of atoms. Further, hydrogen was adjusted so that the ratio of the hydrogen concentration in the polymerization vessel 17 to the propylene concentration was 0.095, ethylene was adjusted so that the ratio of the ethylene concentration to the propylene concentration was 0.020, and the pressure in the polymerization vessel 17 was 2. Propylene monomers were respectively supplied into the polymerization vessel 17 so as to maintain 2.10 MPa and a temperature of 61 ° C. The reaction heat was removed by the vaporization heat of the raw material propylene supplied from the raw material mixed gas supply pipe 19. The unreacted gas discharged from the polymerization vessel 17 was extracted from the reactor system through the unreacted gas extraction piping 20, cooled and condensed, and refluxed to the polymerization reactor 17 through the recycle gas piping 18.
The propylene-ethylene copolymer (b-1) produced in the polymerization vessel 17 is continuously fed from the polymerization vessel 17 through the polymer extraction pipe 21 so that the retained level of the polymer is 45% by volume of the reaction volume. It extracted and supplied to the superposition | polymerization device 26 of the 2nd superposition | polymerization process.
In the polymerization vessel 26, the polymer from the first polymerization step, and hydrogen so that the ratio of the hydrogen concentration in the polymerization vessel 26 to the propylene concentration is 0.021, and the ratio of the ethylene concentration to the propylene concentration is 0.00. Ethylene was supplied to the polymerization vessel 17 so that the pressure in the polymerization vessel 17 was 2.05 MPa and the temperature was maintained at 70 ° C. Further, a polymerization activity inhibitor for adjusting the polymerization amount of the propylene-ethylene copolymer (b-2) was supplied from the pipe 27. The reaction heat was removed by the vaporization heat of the raw material liquefied propylene supplied from the raw material mixed gas pipe 22. The unreacted gas discharged from the polymerization vessel 26 was extracted out of the reactor system through the unreacted gas extraction piping 24, cooled and condensed, and refluxed to the polymerization reactor 26 through the recycle gas piping 23. The propylene polymer produced in the second polymerization step was continuously extracted from the polymerizer 26 through the polymer extraction pipe 25 so that the retained level of the polymer was 50% by volume of the reaction volume. The extracted powder was subjected to gas separation by a gas recovery machine 28, and the powder part was extracted to a recovery system and granulated by a granulation system.
The production rate of the propylene-based polymer was 9.6 T / Hr, the average residence time in the polymerization vessel 17 was 1.9 Hr, and the average residence time in the polymerization vessel 26 was 1.3 Hr. When the catalyst efficiency was determined by dividing the production rate by the supply rate of the solid catalyst component A, it was 88900 g-PP / g-catalyst.
Moreover, when the obtained propylene polymer was analyzed, MFR was 38.9 g / 10min and ethylene content was 5.0 wt%. The PP component (b-1) had an MFR of 71.9 g / 10 min and an ethylene content of 2.5 wt%. When the index about PP component (b-2) was computed, MFR = 8.0g / 10min and ethylene content were 11.3 wt%.
Here, the MFR of the PP component (b-1) is logarithmically calculated from the MFR of the PP component (b-1) and the MFR of the propylene polymer, and the weight ratio of the PP components (b-1) and (b-2). Calculated according to the formula. The ethylene content was calculated from the ethylene content of the PP component (b-1), the ethylene content of the propylene polymer, and the weight ratio of the PP components (b-1) and (b-2). Here, the weight ratio of the PP components (b-1) and (b-2) is calculated from the amount of liquefied propylene supplied to the polymerization tank, and the production amount of the PP component (b-2) is It was 28% based on the total weight. The composition of the propylene-ethylene block copolymer (B) (PP-1) is shown in Table 1.

(3) Polyethylene Metallocene-based low density polyethylene (b): density (JIS K7112) 0.907 g / cm ³ , MFR (JIS K7210, 190 ° C., 2.16 kg load) 12.0 g / 10 min. (Nippon Polyethylene Corporation Kernel KM572)

(4) Nucleating agent (i) Organophosphate metal salt compound nucleating agent ADK STAB NA-11 (NA-11; manufactured by ADEKA Corporation): Corresponding to nucleating agent (A) (ii) Organophosphate metal Salt compound nucleating agent ADK STAB NA21 (NA-21; manufactured by ADEKA): equivalent to nucleating agent (B) (iii) XT386 (XT386; manufactured by BASF): equivalent to nucleating agent (C) ( 5) Neutralizing agent (i) DHT-4A: Hydrotalcite (manufactured by Kyowa Chemical Industry Co., Ltd.)
(6) Antioxidant (i) Phosphorous antioxidant: Irgaphos 168 (IF168; manufactured by BASF), Tris (2,4-di-tert-butylphenol) phosphite (ii) Hindered amine UV stabilizer: TINUVIN622LD ( TNV622; manufactured by BASF), dimethyl oxalate 2- (4-hydroxy-2,2,6,6-tetramethylpiperidine) ethanol condensate

(Examples 1-7, Comparative Examples 1-2)
Propylene polymer, nucleating agent and other additives (antioxidant, neutralizing agent, etc.) prepared in the blending ratios (parts by weight) shown in Table 2, and after dry blending with a super mixer, 35 mm diameter Were melt-kneaded using a twin-screw extruder. Extruded pellets from the die at a die outlet temperature of 230 ° C. The obtained pellets were injection molded by an injection molding machine at a resin temperature of 230 ° C., an injection pressure of 600 kg / cm ^2, and a mold temperature of 40 ° C. to prepare test pieces. The physical properties were measured using the obtained test pieces. The results are shown in Table 2.

  From Table 2, Examples 1-7 are this invention products which mix | blended propylene-ethylene block copolymer (B) with the propylene homopolymer, and are excellent in heat resistance, rigidity, and the balance of an impact, and after AC sterilization. It turns out that transparency is excellent. Especially Examples 4-7 are excellent in balance. On the other hand, Comparative Example 1 does not contain the propylene-ethylene block copolymer (B) and has excellent heat resistance and rigidity, but has low impact resistance, and transparency after AC sterilization is also an example. Inferior to Comparative Example 2 is a blend of metallocene low-density polyethylene to obtain a balance of heat resistance, rigidity and impact resistance, but it can be seen that the transparency after AC sterilization is inferior to that of the Examples.

(Example 8)
Using the pellets obtained in Example 4, the 16th revised Japanese Pharmacopoeia test: 7.02 of the plastic drug container test method 2.1 Transparent according to the test method in the section of polyethylene or polypropylene aqueous injection container , Heavy metal, lead, cadmium, ignition residue, foaming, pH, potassium permanganate reducing substance, ultraviolet absorption spectrum, evaporation residue. As a result, it was confirmed that all items were within the applicable range.

  The present invention relates to a medical propylene-based resin composition and a molded product thereof, and in particular, among medical-use drugs and chemical storage containers, in particular, the 16th revision Japanese Pharmacopoeia 7.02 Plastic Pharmaceutical Container Testing Method. Standards for plastic water injection containers 2.1 Polyethylene or polypropylene water injection containers (4) heavy metals, (5) lead, (6) cadmium, (7) ignition residue, (8) eluate It satisfies the test items, and retains transparency even after excellent heat resistance, rigidity, impact resistance, injection moldability and autoclave sterilization. A storage container filled with a drug solution as a syringe, a medical instrument, and a medical container, which proves to be very useful for obtaining an excellent molded article that passes the 16th revision Japanese Pharmacopoeia general examination. And suitable for kit preparations such as prefilled syringes.

17 Polymerizer (first polymerization process)
18 Recycled gas pipe 19 Raw material mixed gas pipe 20 Unreacted gas outlet pipe 21 Polymer outlet pipe 22 Raw material mixed gas pipe 23 Recycled gas pipe 24 Unreacted gas outlet pipe 25 Polymer outlet pipe 26 Polymerizer (second polymerization step)
27 Pipeline for adding polymerization activity inhibitor 28 Gas recovery machine 29 Bag filter

Claims (6)

A propylene homopolymer polymerized by a Ziegler-Natta catalyst or a propylene copolymer composed of propylene and an α-olefin having a content of less than 1% by weight, conforming to JIS K7210 (230 ° C, 2.16 kg load) 60 to 99 parts by weight of a propylene-based (co) polymer (A) having a melt flow rate (hereinafter sometimes abbreviated as MFR) of 0.5 to 100 g / 10 min, and (Bi) A nucleating agent is added to 100 parts by weight of a propylene-based resin composed of 1 to 40 parts by weight of a propylene-ethylene block copolymer (B) polymerized by a Ziegler-Natta catalyst satisfying the characteristics of (B-iv). A medical propylene-based resin composition containing 0.005 to 0.3 parts by weight and used after high-pressure steam sterilization.
(Bi) Propylene-ethylene copolymer (b-1) having an ethylene content of 0.1 to 3% by weight and MFR of 10 to 300 g / 10 min, an ethylene content of 5 to 20% by weight, and an MFR of 1 to 1 Propylene-ethylene block copolymer (B) composed of propylene-ethylene copolymer (b-2) at 50 g / 10 min
(B-ii) The weight ratio of the propylene-ethylene copolymer (b-1) to the propylene-ethylene copolymer (b-2) is 90:10 to 60:40.
(B-iii) Propylene-ethylene block copolymer (B) has an ethylene content of 2 to 8% by weight.
(B-iv) MFR ratio (b-1 / b-2) of propylene-ethylene copolymer (b-1) and propylene-ethylene copolymer (b-2) is 1 to 30, and propylene-ethylene The MFR of the block copolymer (B) is 10 to 100 g / 10 min. The nucleating agent is 0.01 to 0.3 part by weight of the nucleating agent (A) represented by the following formula (1), and 0.01 to 0.2 nucleating agent (B) represented by the following formula (2). The nucleating agent (C) represented by the following formula (3) is at least one kind selected from the group consisting of 0.005 to 0.03 parts by weight. The medical propylene-based resin composition described in 1.

[Wherein, R ¹ is a direct bond, sulfur, an alkylene group having 1 to 9 carbon atoms or an alkylidene group, and R ² and R ³ are the same or different and each represents a hydrogen atom or an alkyl having 1 to 8 carbon atoms. A group, M is Na, and n is the valence of M. ]

[Wherein, R ¹ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, R ² and R ³ are the same or different and each represents a hydrogen atom or an alkyl group having 1 to 12 carbon atoms; Represents a group III or group IV metal atom of the periodic table, X represents HO— when M represents a group III metal atom of the periodic table, and M represents group IV of the periodic table. When a group metal atom is shown, O = or (HO) _2- . ]

_[R 1 ~R 3: t- butyl]   The medical propylene-based resin composition according to claim 1 or 2, wherein the sterilization method is high-pressure steam sterilization at 100 ° C to 130 ° C.   The medical molded article using the propylene-type resin composition of any one of Claims 1-3.   A kit preparation, wherein the medical molded article according to claim 4 is a kit preparation.   A prefilled syringe, wherein the kit preparation according to claim 5 is a prefilled syringe.

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