JP2008307146A - Medical low-density polyethylene container - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a medical low-density polyethylene container with improved workability and an elution property, which are defects of a conventional medical container using low-density polyethylene. <P>SOLUTION: The medical low-density polyethylene container is made of low-density polyethylene satisfying the following conditions (1)-(6). (1) The density is 910-935 kg/m<SP>3</SP>, (2) MFR is 0.1-4 g/10 min, (3) weight average molecular weight (Mw) and MFR satisfy -9,200×MFR+99,000<Mw<-9,200×MFR+100,700, (4) the quantity of extracted hot water refluxed for 7 hours with pure water 1L and extracted from a sample 470g is not more than 0.02 ml, (5) the number of terminal end vinyl groups per 1,000 carbon atoms is not more than 0.13, and (6) the relation between the melting tension and MFR at 190°C satisfies melt tension (mN)≤116.98×MFR<SP>-0.5383</SP>. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a low-elution pharmaceutical container made of high-pressure low-density polyethylene. More specifically, it conforms to the Japanese Pharmacopoeia and has excellent processability, product appearance, heat resistance, low elution, and transparency, such as infusion solutions, infusion containers containing blood, eye drops containers, nasal containers, oral liquid containers, etc. It relates to a pharmaceutical container.

  With the advancement of advanced medical technology, diversification and convenience of medical containers are required. Disposable specifications for containers are spreading, and the problem of a large amount of waste is also highlighted. In addition to safety, there is an increasing need for plastic materials that can be incinerated.

  An example of a plastic material that is expected to be converted from a glass material is an ampoule application. In the same application, the conventional process of washing the inner wall after blow molding is performed, but the simultaneous filling blow molding method that fills the chemical simultaneously with the blow molding is performed in order to omit the washing process for the purpose of improving productivity. It has been developed. In the simultaneous filling blow molding, since the chemical solution is directly filled in the molten resin, the number of fine particles in the chemical solution is increased as compared with the conventional post-filling method. Accordingly, the polyethylene resin is required to have a reduced number of fine particles, that is, low elution (cleanness).

  Low-density polyethylene obtained by high-pressure radical polymerization has a high melt tension, excellent flowability under high shear, and a blow molded product with a uniform wall thickness and good surface condition. It is used. In particular, polyethylene (tubular product) obtained with a tubular polymerizer has fewer long chain branches and a narrower molecular weight distribution than polyethylene (bessel product) obtained with an autoclave-type polymerizer. This is suitable because a product having a good appearance can be obtained. However, since the tubular product has more elution components than the vessel product, the number of fine particles tended to increase when sterilized. On the other hand, a method of mixing low density polyethylene and linear low density polyethylene has been proposed as a container having excellent heat resistance and transparency and little elution into the content liquid (see, for example, Patent Document 1). However, when the number of fine particles of low density polyethylene is large, it is difficult to extremely reduce the fine particles even in the mixture, and the development of a low-elution pharmaceutical container has been desired.

JP 59-203560 A

    An object of the present invention is to provide a pharmaceutical container that is excellent in appearance (surface skin) of a container and excellent in low elution, which is a disadvantage of a pharmaceutical container using low-density polyethylene produced by a conventional tubular reactor. It is in.

The present invention has been found as a result of intensive studies on the above object. That is, the present invention relates to a pharmaceutical container comprising a high-pressure low-density polyethylene [A] produced using a tubular reactor satisfying the following characteristics (1) to (6).
(1) A density based on JIS K6922-1 is 910 to 935 kg / m ³ ,
(2) Melt mass flow rate (MFR) based on JIS K6922-1 is 0.1 to 4 g / 10 min,
(3) The relationship between the weight average molecular weight (Mw) obtained by gel permeation chromatography and the melt mass flow rate based on JIS K6922-1 satisfies the following conditions.

−9,200 × MFR + 99,000 <weight average molecular weight (Mw) <− 9,200 × MFR + 100,700,
(4) The amount of hot water extracted by reflux extraction of 470 g of sample with 1 L of pure water for 7 hours is 0.02 ml or less,
(5) The number of terminal vinyl groups per 1,000 carbon atoms is 0.13 or less,
(6) The relationship between the melt tension at 190 ° C. and the melt mass flow rate based on JIS K6922-1 satisfies the following conditions.

Melt tension (mN) ≦ 116.98 × MFR ^−0.5383
Hereinafter, the present invention will be described in detail.

  The low-density polyethylene [A] constituting the pharmaceutical container of the present invention can be polymerized in a high-pressure tubular (tubular) reactor. The polymerized in the autoclave reactor has more long chain branches than the polymerized in the tubular reactor, and the swell ratio and melt tension are high. (A phenomenon in which burrs cannot be removed automatically) or the appearance (surface skin) of the product is inferior.

The density of the low density polyethylene [A] constituting the pharmaceutical container of the present invention is 910 to 935 kg / m ³ as a value measured by a density gradient tube method in accordance with JIS K6922-1 (1997). If it is less than 910 kg / m ³ , chemical resistance may decrease due to an increase in components that are likely to elute into the drug. If it exceeds 935 kg / m ³ , stress cracking resistance will be reduced, or the container will have poor flexibility. It becomes.

  The melt mass flow rate at 190 ° C. and a load of 2.16 kg of the low density polyethylene [A] constituting the pharmaceutical container of the present invention is 0.1 to 4 g / 10 minutes, preferably 0.3 to 2 g / 10 minutes. . If it is less than 0.1 g / 10 min, the melt viscosity is too high and the extrusion load is large, and the appearance (surface skin) of the blow container may be impaired. If it exceeds 4 g / 10 min, the melt tension becomes too small, and drawdown (self-weight drooping) cannot be formed vigorously.

  The weight average molecular weight (Mw) in terms of linear polyethylene of the low density polyethylene [A] constituting the pharmaceutical container of the present invention and the melt mass flow rate (MFR) based on JIS K6922-1 are represented by the following formulas. It is in. If it is less than the lower limit of the following formula, the amount of eluted components increases, which is not preferable. When the upper limit of the following formula is exceeded, the appearance (surface skin) of the blow container may be impaired.

−9,200 × MFR + 99,000 <weight average molecular weight (Mw) <− 9,200 × MFR + 100,700
The amount of hot water extracted from 470 g of the low density polyethylene [A] sample constituting the pharmaceutical container of the present invention by refluxing with 1 L of pure water for 7 hours is 0.02 ml or less. When the amount of hot water extraction exceeds 0.02 ml, there is a possibility that the eluted component to the chemical solution increases. In order to reduce the hot water extraction amount to 0.02 ml or less, it is preferable that the MFR is low, the density is high, and the low molecular weight component is small.

  The number of terminal vinyl groups per 1,000 carbon atoms of the low density polyethylene [A] constituting the pharmaceutical container of the present invention is 0.13 or less. If it exceeds 0.13, it tends to deteriorate in the heat history at the time of molding, and there is a possibility that the elution component to the chemical solution increases. In order to reduce the number of terminal vinyl groups to 0.13 or less per 1,000 carbon atoms, the polymerization can be carried out by setting the temperature at the time of polymerization to a low level or by reducing the low molecular weight component.

  The melt tension (mN) and melt mass flow rate (MFR) measured at 190 ° C. of the low density polyethylene [A] constituting the pharmaceutical container of the present invention are in the relationship represented by the following formula. If the following formula is not satisfied, the appearance (surface skin) of the blow container may be impaired. In order to satisfy the following formula, polymerization is carried out in a high-pressure tubular reactor (tubular). If necessary, the melt tension tends to be lowered by lowering the polymerization temperature and raising the polymerization pressure.

Melt tension (mN) ≦ 116.98 × MFR ^−0.5383
The low density polyethylene [A] constituting the pharmaceutical container of the present invention can be obtained by purchasing a commercial product. Specifically, Tosoh Corporation's Petrocene 175K-1 and Petrocene 170K correspond to this.

The present invention further includes 0 to 67 parts by weight of an ethylene / α-olefin copolymer [B] that satisfies the characteristics (7) to (12) with respect to 100 parts by weight of the high-pressure low-density polyethylene [A]. It is preferable that it is a pharmaceutical container consisting of
(7) A copolymer of ethylene and an α-olefin having 3 to 20 carbon atoms,
(8) The density based on JIS K6922-1 is 880 to 940 kg / m ³ ,
(9) The melt mass flow rate based on JIS K6922-1 is 0.1 to 5 g / 10 min,
(10) The ratio (Mw / Mn) of the weight average molecular weight (Mw) and the number average molecular weight (Mn) determined by gel permeation chromatography is 1.5 to 3.0,
(11) There is one endothermic curve peak (melting point) measured by DSC (differential scanning calorimeter),
(12) The residue by the ignition residue test method prescribed in the Japanese Pharmacopoeia is 0.1% by weight or less.

  The ethylene / α-olefin copolymer [B] constituting the pharmaceutical container of the present invention is a copolymer of ethylene and an olefin having 3 to 20 carbon atoms. As the α-olefin, propylene, 1-butene, 1-hexene, 1-octene, 4-methyl-1-pentene, 3-methyl-1-butene, 1-pentene, 1-heptene, 1-nonene, 1-decene, 1-undecene, 1-dodecene, 1- Examples include tridecene, 1-tetradecene, 1-pentadecene, 1-hexadecene, 1-heptadecene, 1-octadecene, 1-nonadecene and 1-eicocene. Two or more of these olefins can be mixed and used.

  There is no particular limitation on the production method of the ethylene / α-olefin copolymer [B] constituting the pharmaceutical container of the present invention. For example, a Ziegler catalyst mainly composed of a titanium-based transition metal, a metallocene, etc. is used as a catalyst system. It can be produced by using any catalyst system such as a main Kaminsky catalyst. As the ethylene / α-olefin copolymer used in the present invention, an ethylene / α-olefin copolymer having an Mw / Mn in the range of 1.5 to 3 is easily obtained, and the composition distribution of ethylene and α-olefin is particularly uniform. Therefore, an ethylene / α-olefin copolymer produced using a Kaminsky-type catalyst mainly composed of metallocene or the like is preferable because the resulting container is excellent in transparency and low elution.

  Examples of such Kaminsky-type catalysts include ionic compounds, clays, which react with metallocene compounds (transition metal compounds) mainly composed of transition metals such as titanium, zirconium, hafnium and the like and organometallic compounds or metallocene compounds to form stable anions. A generally known polymerization catalyst system comprising a combination with a mineral can be used. The Kaminsky catalyst may be used alone or in combination. Examples of the metallocene compound include bis (cyclopentadienyl) titanium dichloride, bis (cyclopentadienyl) zirconium dichloride, bis (cyclopentadienyl) hafnium dichloride, bis (indenyl) titanium dichloride, bis (indenyl) zirconium dichloride, Bis (indenyl) hafnium dichloride, ethylenebis (indenyl) titanium dichloride, ethylenebis (indenyl) zirconium dichloride, ethylenebis (indenyl) hafnium dichloride, diphenylmethylene (cyclopentadienyl) (9-fluorenyl) zirconium dichloride, etc. For example, trimethylaluminum, triethylaluminum, triisopropyl Examples of ionic compounds that react with transition metal compounds to become stable anions include lithium tetrakis (pentafluorophenyl) borate, N, N-dimethylanilinium tetrakis (pentafluorophenyl) borate, and the like. Examples of clay minerals include montmorillonite, hectorite, and saponite.

  In addition, the polymerization method at that time is not particularly limited, and any of a general polymerization method such as a gas phase method, a slurry method, a solution method, and a high pressure method may be used. Further, even one-stage or two-stage or more multi-stage polymerized can be produced by mechanically blending two or more kinds of polymers.

The density of the ethylene / α-olefin copolymer [B] constituting the pharmaceutical container of the present invention is 880 to 940 kg / m as a value measured by a density gradient tube method in accordance with JIS K6922-1 (1997). ³ , preferably 900 to 935 kg / m ³ . Is less than 880 kg / ^{m 3,} poor heat resistance when formed into a container, flexible exceeds 940 kg / ^{m 3,} becomes the transparency is inferior.

  The melt mass flow rate at 190 ° C. and a load of 2.16 kg of the ethylene / α-olefin copolymer [B] constituting the pharmaceutical container of the present invention is 0.1 to 5 g / 10 minutes, preferably 1 to 5 g / 10. Minutes. If it is less than 0.1 g / 10 minutes, the melt viscosity is too high and the extrusion load is large, and the product appearance (surface skin) may be impaired. If it exceeds 5 g / 10 min, the melt tension becomes too small and the drawdown cannot be violently molded.

  Ratio of weight average molecular weight (Mw) and number average molecular weight (Mn) determined by gel permeation chromatography of ethylene / α-olefin copolymer [B] constituting the pharmaceutical container of the present invention (Mw / Mn) ) Is 1.5 to 3.0, preferably 2.0 to 3.0. When Mw / Mn is less than 1.5, the extrusion load increases, and the appearance (surface skin) of the film may be impaired. On the other hand, if it exceeds 3.0, transparency and dissolution may be deteriorated.

  The peak (melting point) of the endothermic curve obtained in the temperature rise measurement by DSC (differential scanning calorimeter) of the ethylene / α-olefin copolymer [B] constituting the pharmaceutical container of the present invention is one. The medicinal container obtained by this is small in temperature dependence of the elastic modulus and excellent in transparency. The endothermic curve is obtained by inserting 5 to 10 mg of sample into an aluminum pan and raising the temperature with DSC. The temperature rise measurement is performed by leaving the sample at 230 ° C. for 3 minutes in advance, then lowering the temperature to −10 ° C. at 10 ° C./min, and then raising the temperature to 150 ° C. at a rate of 10 ° C./min. .

  The residue of the ethylene / α-olefin copolymer [B] constituting the pharmaceutical container of the present invention is 0.1% by weight or less by the ignition residue test method prescribed in the Japanese Pharmacopoeia. If the residue by the ignition residue test method stipulated by the Japanese Pharmacopoeia exceeds 0.1% by weight, the elution of impurities into the contents liquid such as drugs may be concerned, and hygiene may be deteriorated. Since the ignition residue detects a catalyst residue and an inorganic additive, it is preferable to reduce the catalyst residue and not add an inorganic additive in order to reduce the ignition residue to 0.1% by weight or less.

  The ethylene / α-olefin copolymer [B] constituting the pharmaceutical container of the present invention can be produced by the method shown in Examples.

  The resin composition constituting the pharmaceutical container of the present invention has a blending ratio (weight ratio) of the low density polyethylene [A] and the ethylene / α-olefin copolymer [B] of 100/0 to 100/67, particularly It is preferable that it consists of 100 / 0-100 / 45 from which the container excellent in balance of transparency and heat resistance is obtained. Here, when the density is lower than the low density polyethylene [A] / ethylene / α-olefin copolymer [B] = 100/67, the swell ratio becomes large and the workability deteriorates, or the container appearance (surface skin), transparency Is inferior.

  The resin compositions [A] and [B] of the present invention can be obtained by mixing by any method. As a mixing method, a single-screw or twin-screw extruder, an open roll mill, a Banbury mixer, a kneader, a kneader ruder, a method of mixing under mechanical mixing conditions, a method of dry blending to mix at the time of container molding, etc. are adopted. be able to.

  The polyethylene resin constituting the pharmaceutical container of the present invention is not added or used for polyolefins, such as antioxidants, weathering stabilizers, antistatic agents, lubricants, antiblocking agents, organic / inorganic pigments, etc., if necessary Additives to be added may be added. The method of mixing the above-mentioned additives into the resin is not particularly limited, but for example, a method of directly adding in the pellet granulation step after polymerization, or a high concentration master batch is prepared in advance, Examples thereof include a method of dry blending at the time of molding.

  The method for producing the pharmaceutical container of the present invention is not particularly limited, but is an accumulator type or continuous extrusion type extrusion blow molding method, simultaneous filling blow molding method, injection blow molding method, extrusion stretch blow molding method, Examples thereof include blow molding methods such as injection stretch blow molding, inflation molding methods, tube molding methods, injection molding methods, and rotational molding methods. Among them, the blow molding method is preferable, and the simultaneous filling blow molding method that is excellent in productivity is more preferable. For example, the polyethylene resin of the present invention is put into a blow molding machine (Placo) having a 65 mmφ extrusion screw set at 180 ° C., and the parison is extruded at a screw rotation speed of 10 rpm. It is obtained by sandwiching the extruded parison with a mold of a 200 ml container set at 25 ° C., blowing air from a blow pin, filling 100 ml of a chemical solution, and then sealing the mouth.

  Further, the pharmaceutical container of the present invention can be a single layer or a multilayer. In this case, the structure of the layer is not particularly limited, but it is effective to use the present polyethylene resin for the inner layer.

  The pharmaceutical container of the present invention preferably has a thickness of 0.1 to 1.5 mm, and more preferably 0.2 to 1.0 mm.

  The medical container of the present invention is filled with a chemical solution. Examples of the chemical liquid include distilled water, physiological saline, water for injection, eye drops, nasal drops, and washing liquid.

  The pharmaceutical container of the present invention is preferably sterilized, and examples of the sterilization method for sterilization include a high-pressure steam (autoclave) sterilization method and a dry heat sterilization method. In particular, the sterilization temperature at the time of high-pressure steam sterilization is preferably 105 ° C. or less in view of the balance between heat resistance and transparency.

  In the Japanese Pharmacopoeia, there is a standard that the number of fine particles of 5 μm or more contained in water or physiological saline in a pharmaceutical container is 100 particles / ml or less. In the pharmaceutical container of the present invention, the number of fine particles of 1 μm or more is 30 particles / ml or less.

  The low-density polyethylene container for medical use of the present invention conforms to the Japanese Pharmacopoeia and is excellent in product appearance, heat resistance, low elution, and transparency. Therefore, an infusion container for infusion, blood, etc. It is suitably used for pharmaceutical containers such as nasal drops and internal liquid containers.

  EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

  Furthermore, various physical properties of the polyethylene resins in Examples and Comparative Examples were measured by the following methods.

~ Measurement of density ~
The density was measured by a density gradient tube method in accordance with JIS K6922-1 (1997).

~ Measurement of melt mass flow rate ~
MFR was measured at 190 ° C. under a load of 2.16 kg in accordance with JIS K6922-1 (1997).

~ Measurement of weight average molecular weight ~
The weight average molecular weight (Mw) was measured by gel permeation chromatography (GPC). Tosoh Co., Ltd. HLC-8121GPC / HT is used as the GPC apparatus, Tosoh Co., Ltd. TSKgel GMHhr-H (20) HT is used as the column, the column temperature is set to 140 ° C., and 1 is used as the eluent. Measurement was performed using 2,4-trichlorobenzene. A measurement sample was prepared at a concentration of 1.0 mg / mL, and 0.3 mL was injected and measured. The calibration curve of molecular weight is calibrated using a polystyrene sample having a known molecular weight. In addition, Mw was calculated | required as a value of linear polyethylene conversion.

-Measurement of hot water extraction amount-
A flask having an internal volume of 1,000 ml was charged with 470 g of a sample and 1 L of pure water, a glass moisture meter and a reflux condenser were attached, reflux extraction was performed for 7 hours, and the amount of components extracted by the moisture meter was measured.

-Measurement of the number of terminal vinyl groups-
The film obtained by hot pressing the sample and cooling with ice water is infrared-scanned in the range of 4,000 to 400 cm ⁻¹ using FT-IR (SPECTRUM ONE manufactured by PERKIN ELMER), and known from the obtained absorption spectrum. The terminal vinyl group was measured using a calibration curve.

~ Measurement of melt tension ~
Melt tension (MS) was measured with a capillary viscometer (Toyo Seiki Seisakusho, trade name: Capillograph) with a barrel diameter of 9.55 mm, a length (L) of 8 mm, a diameter (D) of 2.095 mm, and an inflow angle of 90. MS was used as the load (mN) necessary for take-up, using an orifice of ° C under the conditions of a resin temperature of 190 ° C and a piston lowering speed of 10 mm / min.

~ Number of peaks (melting point) of endothermic curve ~
Measurement was performed using DSC (trade name: DSC-7, manufactured by Perkin Elmer). A sample of 5 to 10 mg is inserted into an aluminum pan and placed on the DSC, then heated to 230 ° C. at a heating rate of 80 ° C./min, and left at 230 ° C. for 3 minutes. Thereafter, the temperature is lowered to −10 ° C. at a temperature lowering rate of 10 ° C./min, and then the temperature is raised / lowered by the procedure of increasing the temperature from −10 ° C. to 150 ° C. at the rate of 10 ° C./min. The number of peaks (melting point) of the endothermic curve observed when the temperature was increased was evaluated.

-Measurement of ignition residue-
In accordance with the Japanese Pharmacopoeia stipulated by the ignition residue test method, weigh accurately 50 g of the sample, put it in a platinum dish and burn it with a gas burner, and then complete ashing in an electric furnace at 650 ° C x 1 hour The weight of the residue was measured, and the percentage was calculated by calculating the percentage with respect to the initial weight.

~ Processability evaluation ~
A container was prepared by the method shown in Example 1, and the deburring property of the container was evaluated. A sample having a good deburring property was indicated by ◯, and a sample having poor deburring property was indicated by ×.

~ Evaluation of product appearance ~
The inside of the container obtained by the above molding was observed. The case where no sharkskin or melt fracture occurred was rated as “◯”, and the case where it was generated was marked as “X”.

~ Evaluation of heat resistance ~
In accordance with the Japanese Pharmacopoeia, after setting the container produced by the method shown in Example 1 in an autoclave, heat-treating at a temperature of 105 ° C. for 30 minutes, cooling to room temperature, taking out the container, Items were observed and evaluated. The waved state of the container was observed. The case where almost no undulation was observed and the degree of deformation was small was marked with ◯, and the case where the waving of the container was large and the deformation of the container was large was marked with x. The rough skin was observed. The case where no spotted pattern was seen on the surface of the container was marked with ◯, and the case where several spotted patterns were seen on the surface of the container was marked with x.

~ Evaluation of transparency ~
A sample having a width of 9.5 mm and a length of 50 mm was cut out from the vicinity of the center of the body of the container after the heat resistance evaluation, and an ultraviolet-visible spectrophotometer (trade name UV-1600) manufactured by Shimadzu Corporation was used. The transmittance at a wavelength of 450 nm was measured in pure water. More than 55% was accepted and less than 55% was rejected.

-Measurement of the number of fine particles-
After pure water in the container after the heat resistance evaluation was allowed to stand at room temperature for a certain period, the number of fine particles of 0.1 μm or more was measured with a liquid fine particle counter series 4100 manufactured by HIAC / ROYCO. All operations were performed in a Class 1000 clean room.

-Measurement of TOC (total organic carbon)-
After the pure water in the container after the heat resistance evaluation was allowed to stand at room temperature for a certain period, the TOC was measured with a TOC analyzer TOC-V _CSH manufactured by Shimadzu Corporation. TOC indicates the total amount of organic matter that can be oxidized in pure water in terms of the amount of carbon, which is the main component, and the carbon in the organic matter is oxidized to carbon dioxide and quantified by an infrared absorption method.

Synthesis example 1
[Production of ethylene / α-olefin copolymer]
The ethylene / α-olefin copolymers [B1] and [B2] used in Examples and Comparative Examples were produced by the following method.

The polymerization operation, reaction and solvent purification were all performed under an inert gas atmosphere. Moreover, the solvent etc. which were used for the reaction were all purified, dried and deoxygenated by a known method in advance. Furthermore, the compound used for the reaction was synthesized and identified by a known method.
<Preparation of catalyst (A)>
Under a nitrogen atmosphere, triethylaluminum (4.5 mol per aluminum atom) was added and dissolved in 4.6 liters of dehydrated heptane. Diphenylmethylene (cyclopentadienyl) (2,7-di-t-butyl-9-fluorenyl) zirconium dichloride (10 mmol per zirconium atom) was added to the solution, and the resulting red suspension was further mixed with N, N-dimethyl-anilinium hydrochloride-modified hectorite (containing 1 mol of N, N-dimethyl-anilinium hydrochloride per kg of hectorite) powder (300 g) was added to obtain catalyst (A). An aliphatic saturated hydrocarbon solvent (IP solvent 2835 (manufactured by Idemitsu Petrochemical Co., Ltd.)) was added to the catalyst solution to adjust the catalyst concentration to a concentration per zirconium atom (0.5 mmol / L).
<Polymerization>
The polymerization reaction was performed in a tank reactor using the catalyst (A). The polymerization method and conditions of the ethylene / α-olefin copolymer [B1] are as follows. Ethylene, 1-hexene as raw materials, and ethane as a dilution solvent for the reaction were continuously injected into the reactor, and the internal stirring system was rotated at 1,500 rpm to sufficiently stir the reaction system. While maintaining the total pressure at 90 MPa, polymerization was carried out. At that time, the raw material introduction amount was controlled so that the 1-hexene concentration was 23.0 mol%.

Then, the catalyst (A) was continuously supplied from the supply port of the reactor, and polymerization was performed so that the average temperature was maintained at 213 ° C. with the amount of catalyst supplied. The obtained ethylene / α-olefin copolymer [B1] had a melt mass flow rate of 4.0, a density of 923 kg / m ³ , an Mw / Mn of 2.9, a melting point of 1, and an ignition residue of 0.8. It was 03% by weight.

Synthesis example 2
Polymerization was carried out in the same manner as in Synthesis Example 1 except that the 1-hexene concentration during polymerization was 30.0 mol% and the average polymerization temperature was 195 ° C., to obtain an ethylene / hexene-1 copolymer [B2]. The obtained ethylene / α-olefin copolymer [B2] has a melt mass flow rate = 2.0 g / 10 min, a density = 920 kg / m ³ , Mw / Mn = 2.2, a melting point of 1, and an ignition residue. 0.02% by weight.

Example 1
Low-density polyethylene [A1] (product name Petrocene 175K-1, melt mass flow rate = 0.6 g / 10 min, density = 922 kg / m ³ ) manufactured by Tosoh Corporation is manufactured and sterilized under the following conditions. The processability and product properties were evaluated. Workability, product appearance, heat resistance, and transparency were good, and the number of fine particles and TOC were low.

[Simultaneous filling blow molding]
The low density polyethylene resin [A1] is charged into a blow molding machine (Placo) having a 65 mmφ extrusion screw set at 180 ° C., and the parison is extruded at a screw rotation speed of 10 rpm. The extruded parison is sandwiched between molds for a 200 ml container set at 25 ° C., blown with air from a blow pin, filled with 100 ml of pure water, and then sealed at the mouth.

[Sterilization]
The container obtained by the above operation was set in a high-temperature and high-pressure cooking sterilizer manufactured by Hisaka Seisakusho and subjected to heat treatment at 105 ° C. for 30 minutes, and the sample was cooled to room temperature.

Example 2
The same operation as in Example 1 was performed except that the low-density polyethylene resin was changed to [A2] (trade name Petrocene 170K, melt mass flow rate = 1.0 g / 10 min, density = 920 kg / m ³ ) manufactured by Tosoh Corporation. The processability and product properties were evaluated. Workability, product appearance, heat resistance, and transparency were good, and the number of fine particles and TOC were low.

Example 3
The same operation as in Example 1 was carried out except that the low density polyethylene resin was changed to [A3] (trade name Petrocene 05K03A, melt mass flow rate = 3.2 g / 10 min, density = 922 kg / m ³ ) manufactured by Tosoh Corporation. The processability and product properties were evaluated. Workability, product appearance, heat resistance, and transparency were good, and the number of fine particles and TOC were low.

Example 4
Low-density polyethylene [A1] (manufactured by Tosoh Corporation, trade name Petrocene 175K-1, melt mass flow rate = 0.6 g / 10 min, density = 922 kg / m ³ ), 100 parts by weight; After dry blending 25 parts by weight of the α-olefin copolymer [B1] with a tumbler, the same operation as in Example 1 was performed with a blow molding machine set at 210 ° C. to evaluate workability and product physical properties. Workability, product appearance, heat resistance, and transparency were good, and the number of fine particles and TOC were low.

Comparative Example 1
The same operation as in Example 1 was performed except that the low-density polyethylene resin was changed to [A3] (trade name Petrocene 175K, melt mass flow rate = 0.6 g / 10 min, density = 922 kg / m ³ ) manufactured by Tosoh Corporation. The processability and product properties were evaluated. Although the processability, product appearance, heat resistance and transparency were good, the number of fine particles and TOC were large.

Comparative Example 2
The same operation as in Example 1 was performed except that the low-density polyethylene resin was [A4] (trade name Petrocene 170R, melt mass flow rate = 1.0 g / 10 min, density = 920 kg / m ³ , manufactured by Tosoh Corporation). The processability and product properties were evaluated. Although the processability, product appearance, heat resistance and transparency were good, the number of fine particles and TOC were large.

Comparative Example 3
The same operation as in Example 1 was performed except that the low density polyethylene resin was changed to [A5] (trade name Petrocene 05C01A, melt mass flow rate = 0.6 g / 10 min, density = 923 kg / m ³ , manufactured by Tosoh Corporation). The processability and product properties were evaluated. Although the processability, heat resistance and transparency were good and the number of fine particles and TOC were small, the product appearance deteriorated.

Comparative Example 4
The same operation as in Example 1 except that [A7] (trade name Petrocene 360-1, Melt Mass Flow Rate = 1.6 g / 10 min, density = 919 kg / m ³ ) manufactured by Tosoh Corporation was used as the low density polyethylene resin. The processability and product properties were evaluated. Although the processability, heat resistance and transparency were good and the number of fine particles and TOC were small, the product appearance deteriorated.

Comparative Example 5
Low-density polyethylene [A1] (manufactured by Tosoh Corporation, trade name Petrocene 175K-1, melt mass flow rate = 0.6 g / 10 min, density = 922 kg / m ³ ) 100 parts by weight, ethylene After 100 parts by weight of α-olefin copolymer [B2] was dry blended with a tumbler, the same operations as in Example 1 were performed on a blow molding machine set at 210 ° C. to evaluate workability and product physical properties. Although the heat resistance and transparency were good and the number of fine particles and TOC were small, the parison diameter during processing increased, and the deburring property and product appearance deteriorated.

Comparative Example 6
Example 1 except that the low density polyethylene resin was [A8] (trade name NUC polyethylene DND-2450M, melt mass flow rate = 1.0 g / 10 min, density = 921 kg / m ³ , manufactured by Nippon Unicar Co., Ltd.) The process and the physical properties of the product were evaluated. Although the processability, product appearance, heat resistance and transparency were good, the number of fine particles and TOC were large.

Claims (5)

A pharmaceutical container comprising a high-pressure low-density polyethylene manufactured using a tubular reactor that satisfies the following characteristics (1) to (6).
(1) A density based on JIS K6922-1 is 910 to 935 kg / m ³ ,
(2) Melt mass flow rate (MFR) based on JIS K6922-1 is 0.1 to 4 g / 10 min,
(3) The relationship between the weight average molecular weight (Mw) obtained by gel permeation chromatography and the melt mass flow rate based on JIS K6922-1 satisfies the following conditions.
−9,200 × MFR + 99,000 <weight average molecular weight (Mw) <− 9,200 × MFR + 100,700
(4) The amount of hot water extracted by reflux extraction of 470 g of sample with 1 L of pure water for 7 hours is 0.02 ml or less,
(5) The number of terminal vinyl groups per 1,000 carbon atoms is 0.13 or less,
(6) The relationship between the melt tension at 190 ° C. and the melt mass flow rate based on JIS K6922-1 satisfies the following conditions.
Melt tension (mN) ≦ 116.98 × MFR ^−0.5383 It further comprises 0 to 67 parts by weight of an ethylene / α-olefin copolymer satisfying the characteristics (7) to (12) with respect to 100 parts by weight of the high-pressure method low-density polyethylene according to claim 1. The pharmaceutical container according to claim 1.
(7) A copolymer of ethylene and an α-olefin having 3 to 20 carbon atoms,
(8) The density based on JIS K6922-1 is 880 to 940 kg / m ³ ,
(9) The melt mass flow rate based on JIS K6922-1 is 0.1 to 5 g / 10 min,
(10) The ratio (Mw / Mn) of the weight average molecular weight (Mw) and the number average molecular weight (Mn) determined by gel permeation chromatography is 1.5 to 3.0,
(11) The peak (melting point) of the endothermic curve measured by DSC (differential scanning calorimeter) is one,
(12) The residue by the ignition residue test method prescribed in the Japanese Pharmacopoeia is 0.1% by weight or less. The pharmaceutical container according to claim 1 or 2, which is molded by a blow molding method. The medical container according to any one of claims 1 to 3, which is filled with a chemical solution. The pharmaceutical container according to any one of claims 1 to 4, which has been sterilized.