JP2000033112A - Container for liquid medicine - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a container for liquid medicine having sufficient heat resistant deformability and transparency even in the high-pressure steam steriliz ing treatment exceeding 120 deg.C. SOLUTION: This medicine container is made up of a resin container formed by a transparent and soft container wall consisting of a laminated structure, and a chemical treated by high-pressure steam sterilization together with the container is held in it. In this case, the innermost layer of the container wall is made of linear polyethylene (hereinafter called H-PE) with density 0.940 to 0.970 g/cm3, and the total thickness of H-PE layer used to the whole of the container wall is made <=20 μm.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION The present invention relates to a method for sealing an infusion solution, a dialysate, and other medical solutions for medical use in a resin container.
The present invention relates to a chemical solution container which has been subjected to high-pressure steam sterilization together with the container, and more specifically, to heat resistance, particularly at a temperature of 120 ° C.
The present invention relates to a chemical container capable of maintaining heat deformation resistance, flexibility, and transparency even after the above-described high-pressure steam sterilization.

[0002]

2. Description of the Related Art Medical chemical containers are replacing glass containers with resin containers. This is because the resin container is a flexible, non-standard container and does not require an air needle or the like at the time of use, so it is preferable as a medical liquid container, and its incineration disposal is easier than that of a glass container. The resin used for the medical solution container is polyvinyl chloride, ethylene-vinyl acetate, polyethylene or the like. However, polyethylene-based resins have recently been frequently used because of the problem of container disposal and the fact that the contents are not adversely affected.

[0003]

Since a chemical solution container is subjected to a high-pressure steam sterilization treatment, heat-resistant deformation is generally desired, and the container wall is excellent in transparency, flexibility (natural dripability of the content liquid), and the like. It is desired. It is known that a polyethylene container which is a conventional chemical solution container is excellent in transparency and flexibility. However, when such a polyethylene container is subjected to high-pressure steam sterilization, its temperature is at most 115 ° C. If the container is autoclaved at higher temperatures,
Deformation such as wrinkling or uneven wall thickness occurs in the container wall, and blocking occurs in which the container walls are bonded to each other, and thus there is a problem in heat deformation resistance. Further, after the high-pressure steam sterilization, the container wall may be whitened or the like, resulting in poor transparency. For this reason, a polyethylene container having heat resistance is desired. Recently, a medical solution container using high-density polyethylene and having heat deformation resistance has been proposed (Japanese Patent Laid-Open No. 4-2).
No. 66759). In such a conventional medical drug solution container, about 5 to 40% of high density polyethylene is mixed with low density polyethylene in the inner and outer layers. By adding some high-density polyethylene, the heat resistance of the container wall is maintained. An object of the present invention is to provide a flexible chemical solution container having sufficient heat-resistant deformation and transparency even in high-pressure steam sterilization at a temperature of 120 ° C. or higher.

[0004]

SUMMARY OF THE INVENTION The present invention relates to a chemical container comprising a resin container formed of a transparent and flexible container wall having a laminated structure, and a chemical solution which has been subjected to high-pressure steam sterilization together with the container. The innermost layer of the container wall is made of linear polyethylene (hereinafter referred to as H-PE) having a density of 0.940 to 0.970 g / cm ³ , and the total of the H-PE layers used for the entire container wall Is provided with a chemical solution container having a thickness of 20 μm or less.

The chemical solution container according to the present invention comprises a resin container. The resin container is formed by molding from a film or sheet, injection molding, blow molding, or the like. The container wall of the resin container has a laminated structure of resins having different characteristics. In order to form a laminate of different resins on the wall of the resin container, each resin can be co-extruded at the time of resin extrusion molding. For sheets or films,
A laminate can be formed by laminating a plurality of films. The medical solution container contains an infusion solution, an injection, a dialysate, and other medical solutions in the container. The chemical solution is filled in a container, and after sealing, is subjected to high-pressure steam sterilization together with the container. 120 ° C for high pressure steam sterilization
As described above, the sterilization processing time is extremely reduced, and the sterilization processing can be reliably performed. The container wall of the liquid medicine container has such transparency that the state of the liquid medicine can be confirmed, and has such flexibility that the liquid medicine in the container can be naturally dropped from the drip opening so that the air needle or the like is not required at the time of use.

[0006] The innermost layer of the container wall according to the present invention is the above-mentioned H-layer.
The above-mentioned H which is composed of a PE layer and is used for the entire container wall
-The total thickness of the PE layer is 20 µm or less. The above HP
E is a linear polyethylene having a density of 0.940 to 0.970 g / cm ³ , which means a medium-density polyethylene excluding a low-density portion and a high-density polyethylene. The density of the H-PE is particularly 0.942 to 0.965 g / cm ^3.
Is desirably within the range. Linear polyethylene having a density lower than the above does not have sufficient heat deformation resistance. Further, linear polyethylene having a density higher than the above-mentioned density has a limit in production.
In order to adjust the density of the H-PE, the α-olefin may be slightly copolymerized. The number of short-chain branches of the α-olefin is 7 per carbon number of the main chain.
It is desirable that the number is equal to or less than 1000 / c.

The above-mentioned H-PE is obtained by a Ziegler method using a Ti system or a Phillips method using a Cr system, at normal pressure to 100 kg / h.
Manufactured by ionic polymerization under a pressure of the order of cm ² . Further, the L-LDPE is more preferably manufactured using a metallocene catalyst such as bis (cyclopentadienyl) zirconium chloride which has recently been put to practical use.
H-LDPE polymerized with such a catalyst is excellent in transparency and the like due to small structural non-uniformity, and has a more uniform molecular weight distribution even when heated and the like, and thus has less bleeding and may cause blocking. Less is. H-
The PE layer usually has a problem in transparency, and when the thickness on the container wall exceeds 20 μm, the transparency becomes extremely poor. The heat resistance of the outer wall surface of the container was found to be sufficiently effective even when the thickness was 20 μm, particularly 10 μm.
-It is desirable that the thickness of the PE layer is 20 µm or less.
In addition, the above-mentioned H-PE layer can be practically laminated up to a thickness of 5 μm in manufacturing.

[0008] In the chemical solution container according to the present invention thus constituted, even after high-pressure steam sterilization at a temperature of 121 ° C, the above-mentioned H-PE layer does not cause blocking or whitening, etc. There is no wrinkle or pock on the wall surface due to heating. In addition, since the H-PE layer is thin, the transparency of the container wall is sufficiently maintained, and since the H-PE layer does not adversely affect the flexibility of the container wall, the content of the container can be naturally dropped.

[0009] The chemical solution container according to claim 2 of the present invention comprises:
2. The liquid medicine container according to claim 1, wherein the outermost layer of the container wall is the H-PE layer. When the above-described H-PE is used for the outermost layer of the chemical solution container, the outer wall surface also has heat resistance, so that roughening of the outer wall surface during heating and blocking between stacked containers can be avoided. In this case, the thickness of the H-PE layer used for the container wall impairs transparency unless the total thickness of the H-PE layer used for the entire container wall is 20 μm or less. .

[0010] The chemical solution container according to claim 3 of the present invention comprises:
3. The chemical solution container according to claim 2, wherein the intermediate layer of the container wall comprises a polyethylene (hereinafter, referred to as L-PE) layer having a density of less than 0.940 g / cm ³ .
As described above, the total thickness of the innermost layer and the outermost layer of the container wall is 20 μm or less. Only the outermost layer cannot maintain the mechanical strength of a medical container. For this reason, an intermediate layer for maintaining the mechanical strength is required in the container wall. The intermediate layer is desirably transparent and flexible, and is desirably a resin layer that can be sufficiently protected from heating by the innermost layer and the outermost layer. The L-PE is a polyethylene having low density and excellent transparency and flexibility. For this reason, as the intermediate layer of the container wall, 8
When used with a thickness of 0 μm or more, sufficient mechanical strength can be imparted to the container wall.

The L-PE has a density obtained by radical polymerization or ionic polymerization of less than 0.940 g / cm ³ . Linear polyethylene obtained by ionic polymerization is desirable because the density can be adjusted accurately. The density of the L-PE is less than 0.940 g / cm ^3, in particular 0.935g / cm ³ ~0.
It is desirably in the range of 880 g / cm ³ . The polyethylene obtained by the radical polymerization is 1000-3
Produced under high pressure of 000 kg / cm ² ,
By containing 0, it is manufactured with low density. Polyethylene obtained by the above ionic polymerization, ethylene and α-
It is a copolymer with an olefin, and the α-olefin is copolymerized by several percent to introduce short-chain branching to obtain a density of 0.940.
It is a linear polyethylene having a low density of less than g / cm ³ . The density of linear polyethylene can be adjusted by the number of short-chain branches due to α-olefin.
7-60 pieces per 0c / 1000c, especially 10-20
It is desirable that the number be in the range of pcs / 1000c. Therefore,
The L-PE includes a low-density portion of a linear medium-density polyethylene and an ultra-low-density polyethylene.

The α-olefin has at most 12 carbon atoms and includes propylene, butene-1, hexene-1, 4-methylpentene-1, and octene-1. The above-mentioned L-PE is a Ziegler method using a Ti system or a Phillips method using a Cr system.
It is produced by ionic polymerization under a pressure of about 0 kg / cm ² .
Further, the linear polyethylene is more preferably produced by a metallocene catalyst such as bis (cyclopentadienyl) zirconium chloride which has recently been put to practical use. Polyethylene polymerized with such a catalyst is excellent in transparency due to small structural non-uniformity, and also has a more uniform molecular weight distribution than conventional ones even when heated, so there is less bleeding and there is a risk of blocking. Few.

According to a fourth aspect of the present invention, there is provided a drug solution container comprising:
The liquid medicine container according to claim 1, wherein the L-PE is linear polyethylene obtained by ionic polymerization of a metallocene catalyst. As described above, linear polyethylene using a metallocene catalyst has high structural uniformity.
This is because the active site of the metallocene catalyst is a single site. Differential scanning calorimetry (DSC) melting patterns of such linear polyethylene differ from conventional Ziegler-catalyzed linear polyethylene and have a strong single heat absorption peak. Such a linear polyethylene sheet or film is excellent in flexibility, transparency and the like.

According to a fifth aspect of the present invention, there is provided a chemical solution container,
2. The chemical solution container according to claim 1, wherein the outermost layer of the container wall comprises a layer of a mixed resin (hereinafter, referred to as PE-PP) of the L-PE and polypropylene (hereinafter, referred to as PP) and the PE-. The weight ratio of L-PE / PP in the PP layer is in the range of 50/50 to 95/5. The PE-PP layer according to the present invention is obtained by blending the following L-PE with the following PP. The PP is an isotactic, syndiotactic, or atactic polypropylene produced using a Ziegler-Natta catalyst. Further, isotactic, syndiotactic, or atactic polypropylene produced using a metallocene catalyst which has recently been put to practical use is more desirable because of its excellent transparency. It is desirable that the PP has a polymer melting point of 140 ° C. or higher. In the case of polypropylene having the above-mentioned temperature characteristics, when added to the PE-PP, the PE-PP layer can be given sufficient heat deformation resistance. . The PP may be a random copolymer containing at most 8% by weight or less of ethylene or butene. The copolymerized ethylene is P
When P is given flexibility and added to PE-PP, it is effective in maintaining the flexibility of the container wall. However, an ethylene content exceeding the above range is not preferable because it adversely affects the transparency of the container wall.

The PE-PP layer is a mixed resin in which the weight mixing ratio of PE / PP is in the range of 50/50 to 95/5. More preferably, the mixing ratio is in the range of 55/45 to 85/15. P in the PE-PP layer
If the mixing ratio of P is more than 50, the flexibility of the container wall is deteriorated, which adversely affects the spontaneous dropping property of the drug solution container, which is not preferable. If the mixing ratio of PP in the PE-PP layer is less than 5, the heat-resistant deformation of the container wall does not improve, and deformation and whitening occur when the chemical solution container is subjected to high-pressure steam sterilization at a temperature of 121 ° C.

When the container wall is composed of two layers, an innermost layer and an outermost layer, the thickness of the outermost layer is desirably in the range of 100 to 300 μm. When there is an intermediate layer other than the innermost layer and the outermost layer, the intermediate layer serves as a layer for imparting mechanical strength to the container wall. Therefore, the outermost layer is preferably in a range of 10 to 100 μm, particularly 20 to 60 μm. . The PE-PP layer used for the outermost layer has little decrease in transparency,
Maintain the transparency of the container wall. When the thickness of the PE-PP layer increases, the flexibility of the container wall deteriorates. Therefore, when the PE-PP is used as a layer of the container wall, the thickness is desirably 300 μm or less, and if it exceeds the above range, a problem occurs in spontaneous dropping property. PE-
It is not preferable that the PP layer be used for the container wall in a range of less than 10 μm, because it causes difficulty in production.

In the liquid medicine container according to the present invention thus constituted, the transparency of the container wall is sufficiently maintained even after the high-pressure steam sterilization treatment at a temperature of 121 ° C., and the flexibility that allows natural dropping is provided. Have. Also, no wrinkles, uneven thickness, uneven whitening, etc. occur on the container wall. Therefore, the drug solution container can be used as a safe infusion solution container for infusion, a container for peritoneal dialysis, and the like. The intermediate layer of the container wall is desirably composed of the L-PE layer as described above. Further, it is desirable that the L-PE is a linear polyethylene obtained by ionic polymerization of a metallocene catalyst.

[0018]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Preferred embodiments of a chemical solution container according to the present invention will be described below in detail. FIG. 1 is a plan view of a sheet of a drug solution container according to an example and a comparative example. FIG. 2 is a plan view of the drug solution containers according to the example and the comparative example.

Various resins are extruded to produce a film having a predetermined thickness in a stretched or unstretched state, and then the various produced films are appropriately combined and laminated to form a sheet for a container according to the present embodiment or a comparative sheet. The sheet according to the example is manufactured. Each of the sheets 1 is folded at a predetermined position as shown in FIG. Next, the container body 2 is formed by heat-sealing the three edges of the stacked sheets 1. Therefore, the surface on the folded side of the stacked sheets 1 becomes the container inner wall 1A. When the peripheral edge is heat-sealed, the discharge port 3 is inserted between the stacked sheets 1, and the discharge port 3 is fixed to the inner wall surface of the sheet 1 by the heat-sealing seal. Rinse water is injected into the container body 2 from the discharge port 3 to clean the inside of the container body 2 cleanly. Next, a chemical solution 4 is filled from the discharge port 3, and the discharge port 3 is sealed with a rubber stopper 5 to obtain a chemical solution container shown in FIG. Such a chemical container has a temperature of 121.
Autoclaved in autoclave at 20 ° C for 20 minutes.

The production film to be laminated is L-PE
(1), L-PE (2), L-PE (3), L-PE (4), LP
E (5), H-PE (1), H-PE (2), PE-PP (1), P
E-PP (2), PE-PP (3), PE-PP (4) and PE
—PP (5). The properties of each resin are as follows. Table 1 shows the configuration of the laminated sheet obtained by combining the resin sheets.

The above L-PE (1) has a density of 0.922 g / c.
In m ^3, a low-density polyethylene is a radical polymer obtained by the high-pressure process. The L-PE (2) has a density of 0.922 g / cm ³ , an MFR of 0.2 g / 10 min, is a copolymer of ethylene and hexene-1 obtained by a Ziegler catalyst, and has an ethylene chain. Is a linear low density polyethylene. The L-PE (3) has a density of 0.9
It is a copolymer of ethylene and hexene-1 obtained at 22 g / cm ³ , an MFR of 0.2 g / 10 min and obtained by a metallocene catalyst, and is a linear low-density polyethylene having a linear ethylene chain. The L-PE (4) has a density of 0.930 g / cm ³ ,
It is a copolymer of ethylene and hexene-1 obtained with a metallocene catalyst having an MFR of 0.4 g / 10 minutes, and is a linear low-density polyethylene having a linear ethylene chain. L-
PE (5) has a density of 0.935 g / cm ³ and an MFR of 0.9
g / 10 minutes, is a copolymer of ethylene and butene-1 obtained with a metallocene catalyst, and is a linear low-density polyethylene having a linear ethylene chain.

The H-PE (1) has a density of 0.945 g / c
It is a medium-density polyethylene having an MFR of 0.8 g / 10 min, a peak temperature by the DSC method of 129 ° C. and m ³ . H-
PE (2) has a density of 0.953 g / cm ³ and an MFR of 1.0
It is a high-density polyethylene having a peak temperature of 135 ° C. by the DSC method at g / 10 minutes.

The PE-PP (1) is a polypropylene (PP (1) having a density of 0.905 g / cm ³ and an MFR of 1.4 g / 10 min with respect to 70 parts by weight of L-PE (2). )) To 30
It is blended by weight. PE-PP (2)
Is obtained by blending 30 parts by weight of PP (1) with 70 parts by weight of L-PE (3). The PE-PP (3) is
30 parts by weight of PP (1) is blended with 70 parts by weight of L-PE (4). The PE-PP (4) is L-
30 parts by weight of PP (1) is blended with 70 parts by weight of PE (5). The PE-PP (5) is L-PE
(5) 10 parts by weight of PP (1) is blended with 90 parts by weight. The PE-PP (6) is L-PE (3) 5
It is obtained by blending 50 parts by weight of PP (1) with respect to 0 parts by weight. The PE-PP (7) is obtained by blending 70 parts by weight of PP (1) with 30 parts by weight of L-PE (3).

[0024]

[Table 1]

Samples of Examples 1 to 10 and Comparative Examples 1 to 3 were prepared from the respective laminated sheets, and their heat deformation resistance, transparency and spontaneous dropping property were examined. The thermal deformation resistance refers to whether or not blocking or the like occurs on the inner wall of the container, whether or not whitening or white spots occur on the container wall, and whether or not deformation such as wrinkles occurs on the outer surface of the container. In all of these items, those which do not undergo heat deformation are regarded as good, and those in which at least one of them is defective do not have heat deformation resistance. Transparency was measured from the sterilized container by taking a part with a uniform thickness of the container wall and cutting it into a size of about 0.9 x 4 cm to make five pieces, each of which was filled with water to measure the ultraviolet absorption spectrum. The transmittance at a wavelength of 450 nm is measured by an absorbance measurement method using a cell immersed in a cell for use and filled with only water as a control. If the transmittance of the container wall is less than 55%, it is not allowed. The spontaneous dropping property was evaluated by piercing a drip needle into the outlet of the medical container and evaluating the amount of liquid dropped from a venous needle 1.5 m below the position of the drip needle with time. ：: Variation of the drop amount per minute in each section is 8
It is within 0%. ×: Variation of the drop amount per minute in each section is 8
It is less than 0%. Table 2 shows the results of the above evaluation.

[0026]

[Table 2]

As shown in Table 2 above, in all the measurement tests of Examples 1 to 10, sufficient performance was shown. In particular, L-PE (3) to (5) polymerized by a metallocene catalyst in the intermediate layer
The one using was particularly excellent in transparency and heat resistance. As shown in Comparative Example 1 in Table 2 above, H-
When the PE layer does not exist, the L-PE layer directly serves as the inner wall, so that blocking, wrinkling, and L-PE occur on the inner wall of the container.
Whitening occurs in the layer. For this reason, the transparency of the container wall was also reduced. Further, as shown in Comparative Example 2, when the total thickness of the H-LE layer on the container wall was 30 μm, there was a problem in transparency. Further, in the container of Comparative Example 3, delamination occurred between the outer layer and the intermediate layer of the container wall, and the natural dropping property was poor. Also, the transparency test could not be measured.

[0028]

As described above, the chemical solution container according to the present invention comprises a resin container formed of a transparent and flexible container wall having a laminated structure, and accommodates a chemical solution subjected to high-pressure steam sterilization together with the container. In the chemical container, the innermost layer of the container wall is made of linear polyethylene (hereinafter, referred to as H-PE) having a density of 0.940 to 0.970 g / cm ³ .
Since the total thickness of the H-PE layer used for the entire container wall is 20 μm or less, it has sufficient heat deformation resistance and transparency even in high-pressure steam sterilization at a temperature of 120 ° C. or more.

[Brief description of the drawings]

FIG. 1 is a plan view of a sheet of a drug solution container according to an example and a comparative example.

FIG. 2 is a plan view of a drug solution container according to an example and a comparative example.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Sheet 1A Inner wall 2 Container main body 3 Discharge port 4 Chemical solution 5 Rubber stopper

Claims (7)

[Claims] 1. A liquid medicine container comprising a resin container formed of a transparent and flexible container wall having a laminated structure, and a liquid medicine container which is subjected to high-pressure steam sterilization together with the container, wherein the innermost layer of the container wall has a density of Is 0.940 ~ 0.970g /
A chemical solution container comprising linear polyethylene (hereinafter, referred to as H-PE) of cm ³ , wherein the total thickness of the H-PE layer used for the entire container wall is 20 μm or less. 2. The chemical solution container according to claim 1, wherein the outermost layer of the container wall is the H-PE layer. 3. The intermediate layer of the container wall has a density of 0.940.
Polyethylene of less than g / cm ³ (hereinafter referred to as L-PE)
3. The chemical solution container according to claim 2, comprising a layer. 4. The chemical solution container according to claim 3, wherein said L-PE is linear polyethylene obtained by ionic polymerization of a metallocene catalyst. 5. The outermost layer of the container wall comprises a mixed resin (hereinafter, referred to as PE-PP) layer of the L-PE and polypropylene (hereinafter, referred to as PP) and the PE-P.
The weight mixing ratio of L-PE / PP of the P layer is 50/50 to 95.
The container according to claim 1, wherein the ratio is in the range of / 5. 6. The intermediate layer of the container wall has a density of 0.940.
Polyethylene of less than g / cm ³ (hereinafter referred to as L-PE)
The chemical solution container according to claim 5, comprising a layer. 7. The chemical solution container according to claim 6, wherein said L-PE is linear polyethylene obtained by ionic polymerization of a metallocene catalyst.