JPH06169974A - Base material for polyolefin medical care container - Google Patents

Abstract

PURPOSE:To provide a base material for a polyolefin medical care container with heat resistance being enough resistant to high pressure steam sterilization for medical care and having excellent flexibility, transparency, etc. CONSTITUTION:This base material is a one for a polyolefin medical care container forming at least an outermost layer and being a double-layered body, and whose one layer consists of a linear low density polyethylene and whose another consists of a polypropylene and/or a polybutene-1 or a copolymer wherein these are the main components, and the latter layer is formed as the outermost layer.

Description

Detailed Description of the Invention

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a polyolefin-based medical container base material suitable for containers for storing liquids such as blood and medical liquids used in the medical field, tubes for carrying (connection pipes), etc.

2. Description of the Related Art Containers and tubes used in medical treatment such as blood collection, blood transfusion, and liquid transfusion require various performances in addition to safety and hygiene. Among them, flexibility, transparency and heat resistance (high pressure resistance) Steam sterilization) and their balance are important items. Conventionally, in addition to soft polyvinyl chloride, polyethylene-based polymers such as ethylene-vinyl acetate copolymer and low density polyethylene have been mainly used as polymer materials for the above-mentioned applications. Etc. may cause problems. It is pointed out that the ethylene vinyl acetate polymer is superior in transparency and flexibility to ordinary low-density polyethylene (containing no vinyl acetate component) but inferior in heat resistance. In addition, even in ordinary polyethylene,
A low density product with poor transparency and heat resistance and excellent properties of the former two has a low melting point.As a result, heat resistance is not sufficient and the container surface is eroded by steam or small condensation during sterilization. Defects are likely to occur. This applies not only to high-pressure low-density polyethylene, but also to linear low-density polyethylene, which is considered to have relatively good heat resistance, and is disclosed in JP-A-56-92937 and JP-A-61-29095.
4, JP-A-62-44256, JP-A-62.
-53670, JP-A-62-133959, JP-A-63-248633, etc.,
In reality, it is difficult to balance the performance by optimizing or blending the linear low-density polyethylene itself, or by making it into multiple layers (multi-layering). Polypropylene is also a polymer that is widely used in medical containers, and its good heat resistance is far more advantageous than polyethylene.
However, polypropylene is highly rigid (poor in flexibility) and has limited applications. Other than the above, polybutene-1 is also a relatively flexible polyolefin,
There is a defect that transparency is not sufficient.

SUMMARY OF THE INVENTION The present invention has been made to solve the above-mentioned problems of the prior art, particularly the lack of heat resistance of a linear low-density polyethylene medical container.

[Means for Solving the Problems] The inventors of the present invention have found that the linear low density polyethylene (hereinafter referred to as LLD)
It is suitable to solve the problem to have a multilayer structure of a polypropylene (hereinafter referred to as PE) and a polypropylene (hereinafter referred to as PP) -based polymer and / or a polybutene-1 (hereinafter referred to as PB-1) -based polymer, and LLDPE (A And a layer composed of PP and / or PB-1 or a copolymer (B) containing these as the main components, wherein (B) forms at least the outermost layer. The present invention has been achieved, which is intended to have a characteristic base material for a polyolefin-based medical container. In the present invention, LLDPE (A) is a so-called ethylene-α-olefin copolymer,
A small amount (preferably 1 to 10 mol%, more preferably 2 to 8 mol%) of propylene, butene-1, pentene-1, hexene-1, heptene-1, octene-in ethylene.
It can be obtained by copolymerizing α-olefins such as 1, decene-1, 4-methylpentene-1 by a low pressure method or an intermediate pressure method, and has transparency, flexibility, heat resistance, moldability, mechanical properties, etc. Considering that the density is 0.905 to 0.935 g / cm
³ , more preferably 0.910 to 0.930 g / cm ³ , and the melt flow rate (MFR) at a temperature of 190 ° C. and a load of 2,160 g is preferably 0.1 to 3.
10, more preferably 0.5 to 5.0. Next, of (B) in the present invention, PP or a copolymer containing it as a main component (hereinafter referred to as PP-based polymer) is an ordinary isotactic or syndiotactic type obtained by using a stereoregular polymerization catalyst. PP
Is a crystalline polymer containing as a main component. These are appropriately selected, but from the viewpoint of flexibility, a copolymer having a particularly high randomness is advantageous. As the comonomer, ethylene, butene-1, pentene-1, hexene-1,
C2-C12 α-olefins such as octene-1, decene-1, dodecene-1, 4-methylpentene-1 are good, and the comonomer amount is about 3-40 mol%, more preferably 5-30 mol%. The degree is appropriate. A particularly preferable PP polymer is a flexural modulus (JISK7203).
Of less than 6,000 kg / cm ² Vicat softening point (JIS
K7206) is 100 ° C. or higher, which is preferable in terms of the balance of flexibility, transparency, and heat resistance. The PP polymer preferably has an MFR of 0.3 to 40, more preferably 0.5 to 30 at a temperature of 230 ° C. and a load of 2,160 g in view of moldability and mechanical properties of the molded product. In (B), polybutene-1 or a copolymer containing it as a main component (hereinafter referred to as PB-1 polymer) means so-called isotactic PB-1 or a copolymer containing it as a main component, It is manufactured by a known method. In the case of a copolymer, the comonomer used is α-, such as ethylene, propylene, pentene-1, hexene-1, octene-1, 4-methylpentene-1.
Olefins are preferred. These are introduced in order to improve the flexibility and transparency of PB-1, but when the melting point (the melting point of homo PB-1 is 125 to 130 ° C.) is too low, the heat resistance becomes poor, so the copolymerization component. It is preferable to suppress the introduction amount of 10 mol% or less, more preferably 5 mol% or less. Considering the moldability and mechanical properties of the product, the PB-1 polymer has a temperature of 190 ° C and a load of 2,160 g.
Has an MFR of 0.2 to 30, more preferably 0.5 to
25 is good. The PP-based polymer and the PB-1-based polymer are excellent in compatibility and miscibility in arbitrary ratios, and therefore (B) may be composed of both components. As described at the beginning, the present invention provides a multilayer body comprising a layer comprising (A) and a layer comprising (B),
(B) forms at least the outermost layer. The heat-resistant (B) layer is the outermost layer (the “outermost layer” in the present invention means the “layer that forms the outer wall surface of the container or tube”) so that avatars do not occur in the (A) layer during high-pressure steam sterilization. Meaning) is formed. In addition to the outermost layer, (B) means the innermost layer (the "innermost layer" in the present invention means "layer forming the inner wall surface of the container or tube"), and avatars are relatively rare during steam sterilization. ) Or an intermediate layer, and (A), (B) and an adhesive layer (usually the compatibility between (A) and (B) is small, so direct adhesion is not possible and an adhesive polymer is required). It is possible that a polymer component other than the above may form a part of the layer of the multilayer body. In addition,
As the above-mentioned adhesive polymer, ethylene-propylene copolymer is useful. For example, Mitsui Petrochemical Industry Co., Ltd.
Tuffmer A and Tuffmer P manufactured by the company are used. In addition, the flexibility, transparency, heat resistance, required for the use of the substrate for medical containers,
Generally, the substrate has a total thickness of 50 to 1,000 μm, and more preferably 80 to 800, although it depends on strength and the like.
The outermost layer (B) has a thickness of 5 to 100 μm, more preferably 10 to 50 μm. It is needless to say that the thicker the layer (B), the better the heat resistance and the less avatars are generated during sterilization, but the substrate tends to be hard. Also,
It is desirable that the adhesive layer be as thin as possible.
0 μm, more preferably about 2 to 20 μm is recommended. Next, in the present invention, a medical container means a container (including a bag) or a tube for storing or transporting a liquid to be treated in medicine such as blood and medical liquid, and such a product can be obtained by a generally known method. In the case of a container (A),
The temperature of (B) and the adhesive polymer is not lower than the flow initiation temperature, preferably 170 to 260 ° C, more preferably 175 to 2
Extruded at 55 ° C through a T-die for multilayer extrusion or a tubular die for multilayer extrusion (it is desirable to cool the casting roller or sheet with water to suppress crystallization), and obtain the obtained flat sheet or tubular The sheet, parison, etc. may be processed into a predetermined thickness and shape by appropriately utilizing techniques such as thermoforming, blowing, stretching, cutting, and heat sealing. Further, it may be in a non-stretched state or a stretched state. In the case of tubes, the extrusion method is the most suitable. Roughening (embossing) of the inner or outer surface of the container or tube for the purpose of improving the blocking resistance, addition of a slip agent, an anti-blocking agent, etc. may be performed without departing from the scope of the present invention. Polymers, plasticizers, inorganic fillers, stabilizers, etc. may be added. The base material of the present invention is useful as a blood component storage container and as a container for physiological saline, electrolyte solution, dextran preparation, mannitol preparation, saccharide preparation, amino acid preparation and the like.

The present invention will be described in more detail with reference to the following examples. (1) Experimental method Polymers used: Polymers shown in Table 1 were used in combination. Preparation of sheet: The pellets were melted separately in an extruder and fed to a three-kind three-layer T-die (lip length 400 mm, lip width 0.8 mm), and a sheet having (C) (adhesive layer) as an intermediate layer was prepared. The film was extruded at 180 to 220 ° C., cooled with a casting roller kept at 15 ° C., trimmed, and a sheet having a thickness of 350 μm and a width of 300 mm was wound at a speed of 6 m / min. Measurement of Transparency of Sheet: The water transmittance of the sheet obtained in 4. at a wavelength of 450 nm was measured with a Shimadzu double beam type self-recording spectrophotometer UV-300. Further, the sheet was cut into a dumbbell shape, and the tensile modulus was measured according to JIS K7113, and used as a measure of flexibility. Heavy metal and eluate test: The sheet obtained in accordance with the Japanese Pharmacopoeia general test method “Plastic container test method for infusion” was tested. High-pressure steam sterilization test: 150m for the sheet obtained in
It was cut into a size of m × 250 mm, and two sheets were stacked and heat-sealed (sealing layer (A) layer) to prepare a bag, and 800 ml of physiological saline was put therein and sealed. The container containing the chemical solution was placed in a retort type high-pressure steam sterilizer, and the temperature was 110 ° C.
The treatment was performed under the conditions of a gauge pressure of 1.8 kg / cm ² and a time of 40 minutes. After cooling to room temperature and standing for 48 hours, the occurrence of avatars on the surface of the bag was observed.

[Table 1]

[Table 2] (2) Experimental results (see Table 2) Extrusion molding of the sheet was successful, and foreign matter, foaming, etc. were not observed in any composition, and a sheet with high uniformity was obtained. It was also confirmed that the heavy metals and eluates were compatible with the Japanese Pharmacopoeia in any composition. As shown in Table 2, the relationship between the sheet structure, the light transmittance, the tensile elastic modulus, and the occurrence of avatars (having a circular shape with a diameter of 1 to 10 mm and being whitened) during sterilization, (B) as the outermost layer It can be seen that the container made of the sheet has an excellent balance of transparency, flexibility and heat resistance.

Industrial Applicability As described above, the medical container substrate of the present invention skillfully utilizes the effect of the problem of LLDPE solved by coating with a layer of PP or PB-1. It has good properties and has high industrial value.

[Procedure amendment]

[Submission date] December 9, 1992

[Procedure Amendment 1]

[Document name to be amended] Statement

[Correction target item name] Full text

[Correction method] Change

[Correction content]

[Document name] Statement

Title of the invention: Base material for polyolefin medical container

[Claims]

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a polyolefin-based medical container base material suitable for containers for storing liquids such as blood and medical liquids used in the medical field, tubes for carrying (connection pipes), etc.

[0002]

2. Description of the Related Art Containers and tubes used in medical treatment such as blood collection, blood transfusion, and liquid transfusion require various performances in addition to safety and hygiene. Among them, flexibility, transparency and heat resistance (high pressure resistance) Steam sterilization) and their balance are important items. Conventionally, in addition to soft polyvinyl chloride, polyethylene-based polymers such as ethylene-vinyl acetate copolymer and low density polyethylene have been mainly used as polymer materials for the above-mentioned applications. Etc. may cause problems. It is pointed out that the ethylene vinyl acetate polymer is superior in transparency and flexibility to ordinary low-density polyethylene (containing no vinyl acetate component) but inferior in heat resistance. In addition, even in ordinary polyethylene,
A low density product with poor transparency and heat resistance and excellent properties of the former two has a low melting point.As a result, heat resistance is not sufficient and the container surface is eroded by steam or small condensation during sterilization. Defects are likely to occur. This applies not only to high-pressure low-density polyethylene, but also to linear low-density polyethylene, which is considered to have relatively good heat resistance, and is disclosed in JP-A-56-92937 and JP-A-61-29095.
4, JP-A-62-44256, JP-A-62.
-53670, JP-A-62-133959, JP-A-63-248633, etc.,
In reality, it is difficult to balance the performance by optimizing or blending the linear low-density polyethylene itself, or by making it into multiple layers (multi-layering).

Polypropylene is also a polymer widely used in medical containers, and its good heat resistance is far more advantageous than polyethylene. However, polypropylene is highly rigid (poor in flexibility) and has limited applications.

In addition to the above, polybutene-1 is also a relatively flexible polyolefin, but it has the drawback of insufficient transparency.

[0005]

SUMMARY OF THE INVENTION The present invention has been made to solve the above-mentioned problems of the prior art, particularly the lack of heat resistance of a linear low-density polyethylene medical container.

[0006]

[Means for Solving the Problems] The inventors of the present invention have found that the linear low density polyethylene (hereinafter referred to as LLD)
It is suitable to solve the problem to have a multilayer structure of a polypropylene (hereinafter referred to as PE) and a polypropylene (hereinafter referred to as PP) -based polymer and / or a polybutene-1 (hereinafter referred to as PB-1) -based polymer, and LLDPE (A And a layer composed of PP and / or PB-1 or a copolymer (B) containing these as the main components, wherein (B) forms at least the outermost layer. The present invention has been achieved, which is intended to have a characteristic base material for a polyolefin-based medical container.

In the present invention, LLDPE (A) is a so-called ethylene-α-olefin copolymer, which is a small amount of ethylene (preferably 1 to 10 mol%,
More preferably 2 to 8 mol% of propylene, butene-
It is obtained by copolymerizing α-olefins such as 1, pentene-1, hexene-1, heptene-1, octene-1, decene-1, 4-methylpentene-1 by a low pressure method or an intermediate pressure method, but it is transparent. Density is 0.905 to 0.935g considering properties, flexibility, heat resistance, moldability, mechanical properties, etc.
/ Cm ³ , more preferably 0.910 to 0.930 g / c
often the m ^3, temperature 190 ° C., load 2,160g
The melt flow rate (MFR) in (1) is preferably 0.1 to 10, more preferably 0.5 to 5.0. Next, in (B) of the present invention, P
P or a copolymer containing P as a main component (hereinafter referred to as PP-based polymer) is a crystalline polymer containing an ordinary isotactic or syndiotactic type PP as a main component, which is obtained by using a stereoregular polymerization catalyst. . These are appropriately selected, but from the viewpoint of flexibility, a copolymer having a particularly high randomness is advantageous.

As the comonomer, ethylene and butene-
Α-olefins having 2 to 12 carbon atoms such as 1, pentene-1, hexene-1, octene-1, decene-1, dodecene-1, 4-methylpentene-1 are preferable, and the comonomer amount is 3 to 40 mol%. Degree, more preferably 5 to 30
About mol% is suitable.

A particularly preferred PP polymer has a flexural modulus (JISK7203) of 6,000 kg / cm ² or less and a Vicat softening point (JISK7206) of 100 ° C. or more, and has a balance of flexibility, transparency and heat resistance. It is preferable from the point of. The PP polymer has a temperature of 230 ° C. and a load of 2,16 due to its moldability and mechanical properties of the molded product.
MFR at 0 g is 0.3 to 40, more preferably 0.
It is preferably 5 to 30. Further, of (B), polybutene-1 or a copolymer containing this as a main component (hereinafter referred to as PB
-1 type polymer) means so-called isotactic PB-1 or a copolymer containing this as a main component, and is usually produced by a known method. In the case of the copolymer, the comonomer used is preferably an α-olefin such as ethylene, propylene, pentene-1, hexene-1, octene-1, 4-methylpentene-1.

These are introduced to improve the flexibility and transparency of PB-1. However, if the melting point (the melting point of homo PB-1 is 125 to 130 ° C.) is too low, the heat resistance becomes poor. The introduction amount of the copolymerization component is about 10 mol% or less,
More preferably, it should be suppressed to 5 mol% or less. Considering the moldability and mechanical properties of the product, the PB-1 polymer has an MFR at a temperature of 190 ° C and a load of 2,160 g.
Is preferably 0.2 to 30, more preferably 0.5 to 25.

Since the PP polymer and the PB-1 polymer are excellent in compatibility and miscibility at any ratio, (B) may be composed of both components. As described at the beginning, the present invention provides a multilayer body comprising a layer comprising (A) and a layer comprising (B),
(B) forms at least the outermost layer. The heat-resistant (B) layer is the outermost layer (the “outermost layer” in the present invention means the “layer that forms the outer wall surface of the container or tube”) so that avatars do not occur in the (A) layer during high-pressure steam sterilization. Meaning) is formed. In addition to the outermost layer, (B) means the innermost layer (the "innermost layer" in the present invention means "layer forming the inner wall surface of the container or tube"), and avatars are relatively rare during steam sterilization. ) Or an intermediate layer, and (A), (B) and an adhesive layer (usually the compatibility between (A) and (B) is small, so direct adhesion is not possible and an adhesive polymer is required). It is possible that a polymer component other than the above may form a part of the layer of the multilayer body. In addition,
As the above-mentioned adhesive polymer, ethylene-propylene copolymer is useful. For example, Mitsui Petrochemical Industry Co., Ltd.
Tuffmer A and Tuffmer P manufactured by the company are used.

The total thickness of the base material is generally 50 to 1,000 μm, and more preferably, though it depends on the flexibility, transparency, heat resistance, strength, etc. required for the use of the base material for medical containers. Is 80 to 800 μm, and the outermost layer (B) is 5 to 100 μm, and more preferably 10 to 50 μm. It is needless to say that the thicker the layer (B), the better the heat resistance and the less avatars are generated during sterilization, but the substrate tends to be hard. The adhesive layer is preferably as thin as possible, and is 1 to 30 μm, more preferably 2 to
20 μm is recommended.

The term "medical container" as used in the present invention means a container (including a bag) or a tube for storing or carrying a liquid handled in medicine such as blood or medical liquid. can get. In the case of a container, (A), (B) and the polymer for adhesion are heated to a temperature above the flow initiation temperature, preferably 170 to 260 ° C, more preferably 1
Extruded through a T-die for multilayer extrusion or a tubular die for multilayer extrusion at 75 to 255 ° C (it is desirable to cool the casting roller or sheet with water to suppress crystallization), and obtain a flat sheet or tube The sheet, parison or the like may be processed into a predetermined thickness or shape by appropriately utilizing techniques such as thermoforming, blowing, stretching, cutting, and heat sealing. In the unstretched state,
It may be in a stretched state. In the case of tubes, the extrusion method is the most suitable. Roughening (embossing) of the inner or outer surface of the container or tube for the purpose of improving the blocking resistance, addition of a slip agent, an anti-blocking agent, etc. may be performed without departing from the scope of the present invention. Polymers, plasticizers, inorganic fillers, stabilizers, etc. may be added.

The substrate of the present invention is used as a blood component storage container,
It is also useful as a container for physiological saline, electrolyte solution, dextran preparation, mannitol preparation, saccharide preparation, amino acid preparation and the like.

[0015]

The present invention will be described in more detail with reference to the following examples.

(1) Experimental method Polymers used: Polymers shown in Table 1 were used in combination.

Preparation of sheet: Pellets of 3 were separately melted by an extruder, and three kinds of three layers type T die (lip length 4
(C) (adhesive layer) as an intermediate layer is extruded at 180 to 220 ° C., cooled by a casting roller kept at 15 ° C., and trimmed to a thickness. A sheet having a width of 350 μm and a width of 300 mm was wound at a speed of 6 m / min.

Measurement of Transparency of Sheet: The sheet obtained in the above was measured for transmittance in water at a wavelength of 450 nm with a Shimadzu double beam type self-recording spectrophotometer UV-300. Also, the sheet is cut into a dumbbell shape and JISK7
The tensile modulus was measured according to 113 and used as a measure of flexibility.

Heavy metal and eluate test: The sheet obtained in accordance with the Japanese Pharmacopoeia General Test Method “Plastic Container Test Method for Infusion” was tested.

High-pressure steam sterilization test: The sheet obtained in the above is cut into a size of 150 mm × 250 mm, two sheets are stacked and heat-sealed (sealing layer is (A) layer) to prepare a bag, and physiological saline is used. 800 ml of water was added and sealed. The container containing the chemical solution was placed in a retort type high-pressure steam sterilizer and treated under the conditions of a temperature of 110 ° C., a gauge pressure of 1.8 kg / cm ² , and a time of 40 minutes. After cooling to room temperature and standing for 48 hours, the occurrence of avatars on the surface of the bag was observed.

[0021]

[Table 1]

[0022]

[Table 2]

(2) Experimental results (see Table 2) Extrusion molding of the sheet was successful, and no foreign matter or foaming was observed in any of the compositions, and a highly uniform sheet was obtained. It was also confirmed that the heavy metals and eluates were compatible with the Japanese Pharmacopoeia in any composition.

As shown in Table 2, the relationship between the sheet structure, the light transmittance, the tensile elastic modulus, and the occurrence of avatars (having a circular shape with a diameter of 1 to 10 mm and being whitened) during sterilization are shown in Table 2.
It can be seen that the container made of the sheet having (B) as the outermost layer has an excellent balance of transparency, flexibility and heat resistance.

[0025]

Industrial Applicability As described above, the medical container substrate of the present invention skillfully utilizes the effect of the problem of LLDPE solved by coating with a layer of PP or PB-1. It has good properties and has high industrial value.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Office reference number FI technical display location A61J 1/00 331 A 370

Claims (1)

[Claims] 1. A multi-layer body comprising a layer made of linear low density polyethylene (A) and a layer made of polypropylene and / or polybutene-1, or a copolymer (B) containing these as the main components, (B) forms at least the outermost layer, a polyolefin-based medical container substrate.