JPH0999036A - Vessel for medical treatment - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a vessel for medical treatment which has excellent resilience, transparency and heat resistance, does not yield eluate and has no problems in a discarding treatment by forming the vessel of a sheet contg. polypropylene(PP) which is produced by using a metallocene catalyst and has a m. p. below a specific temp. as a forming layer. SOLUTION: This vessel for medical treatment is formed of the sheet contg. the PP which is produced by the metallocene catalyst and has the m. p. below 140 deg.C in the forming layer. The PP produced by the metallocene catalyst has an extremely narrow mol.wt. distribution as compared with ordinary PP which is produced by heterogeneous Titanium catalyst, has a lower stereoregularity and constitutes a uniform molecular structure. Then, the vessel has the excellent transparency and has the extremely little low mol.wt. matter and amorphous matter even in the case of the low melting PP and, therefore, the vessel has no stickiness and the elution components thereof are extremely slight.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a container, particularly a soft bag, for containing a liquid handled in the medical field such as blood and liquid medicine.

[0002]

2. Description of the Related Art Container materials used in the medical field such as blood sampling, blood transfusion, and liquid transfusion are required to have 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, as the polymer material for the above-mentioned applications, in addition to soft polyvinyl chloride, polyethylene-based polymers such as ethylene-vinyl acetate copolymer and low-density polyethylene (high-pressure low-density polyethylene or Ziegler-Natta catalytic linear low-density polyethylene) have been mainly used. Although used, soft polyvinyl chloride may cause problems in elution and disposal of plasticizers. The ethylene-vinyl acetate copolymer is excellent in transparency and flexibility as compared with ordinary low-density polyethylene (containing no vinyl acetate component), but is inferior in heat resistance and requires heat treatment such as radiation crosslinking. In addition, ordinary low-density polyethylene has insufficient flexibility, transparency, and heat resistance, and it is difficult to meet these requirements even with a relatively balanced Ziegler-Natta catalyst linear low-density polyethylene.

Polypropylene is also a polymer widely used in medical containers. Its good heat resistance is far superior to that of polyethylene, and its transparency is relatively excellent, but it has high rigidity. It is poor in flexibility, and has a high melting point, which makes it difficult to perform heat sealing and has a difficulty in bag making.
Copolymerization with other monomers (for example, ethylene and butene-1) to soften polypropylene and blending with a softening agent (for example, styrenic elastomer) are typical examples. In the former, in order to increase flexibility, When a container (sheet) is made of a polymer containing a large amount of comonomer, the problem of stickiness on the surface occurs (due to low molecular weight components and amorphous components). In the latter case, in addition to the problem of blocking due to the increase in the tackiness of the sheet surface when introducing a softener in the blend, the moldability and processability are deteriorated due to the deterioration of the sheet forming performance, and the price of the softener is likely to be limited. .
The "polypropylene" referred to here is a normal crystalline polypropylene produced with a heterogeneous titanium catalyst.

[0004]

SUMMARY OF THE INVENTION The present invention has been made to solve the drawbacks of polypropylene-based medical containers among the above-mentioned problems of the prior art.

[0005]

Means for Solving the Problems What has been clarified in the study by the present inventors is that the use of a metallocene catalyst-based polypropylene having a relatively low melting point leads to the solution of the problems. The present invention is based on a medical container including polypropylene (hereinafter referred to as M-PP) having a temperature of 140 ° C or less as a forming layer. Polypropylene produced with a metallocene catalyst is a "normal" polypropylene produced with a heterogeneous titanium catalyst (hereinafter PP).
The effect of a homogeneous catalyst is exhibited, the molecular weight distribution is very narrow, and the random molecular structure is rich and uniform, resulting in excellent transparency and low molecular weight substances even in low melting point products. It is well known that the amount of amorphous material (atactic polymer) is very small, so that it is not sticky and the amount of eluted components is very small.
-Although it is clear that PP is naturally flexible,
It has been found that its good transparency and flexibility are retained even after autoclaving.

M-PP in the present invention is Kaminsky-Sinn
Metallocene catalysts, which are also called catalysts (also called single-site catalysts or homogeneous catalysts by focusing on the fact that the properties of active sites are the same) (generally, cyclopentadienyl-based and indenyl-based transition metals such as Zr, Hf, and Ti) Or polypropylene having a melting point of 140 ° C. or lower, the degree of isotactic or syndiotactic stereoregularity, 2,1-bond (head-head bond or It is produced by controlling the content of (tail-to-tail bond) or 1,3-bond (trimethylene bond). In addition, ethylene, butene-1, hexene-
1, small amounts of α-olefins such as octene-1 (2-
20 mol%) copolymerized copolymer. Regarding the production method of M-PP, for example, Kazuo Soga et al., “Chemical Society of Japan, New Industrial Chemistry Series, Polymerization Process Technology) -Polyolefin” (Dainippon Book Co., Ltd. 1994)
Published annually).

The melting point of M-PP in the present invention is 14
The requirement is 0 ° C or lower. This is because if the melting point exceeds 140 ° C., the rigidity becomes high and the flexibility is poor. Considering the high-pressure steam sterilization temperature (generally performed at 100 to 121 ° C), the preferable melting point is 120 to 135 ° C.
In this region, the bending elastic modulus of M-PP is about 4,000 kg / c.
Provided is an infusion container (bag) excellent in self-draining property (property of being able to be drained without a needle during infusion), which is not more than m ² . Considering the moldability and mechanical properties of the molded product (container sheet), the temperature is 230 ° C and the load is 2,16.
MFR (melt flow rate) at 0 g is 0.3-
15 is more preferable, and 0.5 to 10 is more preferable. As described above, the sheet forming the medical container of the present invention is MP
P is included as a forming layer, and the inclusion of P as a forming layer here means that the sheet is composed of a layer of M-PP alone or M-PP.
This means that it may be a multilayer body in which PP is at least one layer and other polymer is at least one layer.
In the latter case, the mechanical properties (strength, elongation, etc.) of the container (sheet), moldability, heat sealability, gas (oxygen, carbon dioxide,
(Others such as water vapor) is adopted to adjust / improve barrier properties and the like, and as the above-mentioned "other polymer" forming a multilayer body, polyethylene, polybutene-1, poly-4-methylpentene-1, ethylene-vinyl alcohol copolymer,
Examples thereof include polyester, polyamide and polyurethane. In some cases, "normal PP" or "M-PP having a melting point of higher than 140 ° C" may be used.

Of note here is the thickness of the "other polymer". That is, in the case of a polymer having high rigidity, it is preferable to make the layer thin in order to exhibit the flexibility and the transparency which are the gist of the present invention, and the thickness per layer is 0.0
It is preferably 8 mm or less, more preferably 0.05 mm or less. Further, the thickness of the entire sheet is preferably 0.05 to 0.8 mm, more preferably about 0.08 to 0.6 mm. In the present invention, the medical container means a container for storing a liquid to be treated in medicine such as a liquid medicine for storing body fluid such as blood, an infusion solution, a liquid medicine such as a peritoneal dialysis solution, and such a product is generally known. can get. That is, M-PP and other polymers are extruded through a T die or a circular die at a temperature above the flow initiation temperature, preferably 160 to 240 ° C., and the obtained flat sheet, tubular sheet, parison, etc. It may be processed into a predetermined shape by appropriately utilizing techniques such as forming, blowing, cutting, and heat sealing. It is also possible to adopt the injection blow molding method. The sheet may be unstretched or stretched, but in consideration of the sealing property, the unstretched state is preferred. In order to prevent blocking between sheets, especially in the above-mentioned multilayer body, when a polymer that easily blocks such as polyethylene is used), roughening (embossing) the inner surface or outer surface of the container, blocking prevention Other polymers, softening agents, inorganic fillers, stabilizers, colorants and the like may be added within the range not impairing the gist of the present invention by adding agents and slip agents. It goes without saying that addition of a styrene-based elastomer such as a block (polystyrene-ethylene butylene copolymer-polystyrene) (SEBS) or a block (polystyrene-ethylene propylene copolymer-polystyrene) (SEPS) is not hindered. INDUSTRIAL APPLICABILITY The present invention is useful as a container for storing blood or blood components, an infusion solution such as physiological saline, an electrolyte solution, a dextran preparation, a mannitol preparation, a saccharide preparation, an amino acid preparation, a fat emulsion, or a container for peritoneal dialysate.

An example of application of the medical container of the present invention is a so-called "multi-chamber container". For example, in the case of infusion, since a liquid containing an amino acid and glucose is likely to be deteriorated due to the Maillard reaction, each component is stored in a separate closed system and often mixed immediately before administration to a patient. At this time, in order to perform the mixing operation aseptically (closed system) and to facilitate the operation, a container divided into a plurality of storage chambers is used, and different infusion components are stored in each of the storage chambers. , A method in which the storage chambers divided just before use are made to communicate with each other in a closed system by some means has been put into practical use. The container used here is a multi-chamber container, one of which is the easily peelable type. That is, the seal of the partition wall of the accommodation space is relatively stable and has an adhesive strength that can be easily broken during mixing (in use). The technical point is that the partition wall seal of the storage space is relatively stable and difficult to break during manufacturing or transportation, and has a sealing strength that can be easily broken by hand, jig, etc. during use (mixing). On the other hand, the boundary portion (peripheral portion of the container) connected to the external environment (atmosphere) has a large strength that is not broken by these operations. Therefore, it is important to select the material forming the container, but the M-PP of the present invention can adjust the seal strength appropriately, and its transparency and flexibility are also in a practical range. It is suitable as a type of multi-chamber container.

[0010]

The present invention will be described more specifically with reference to the following examples. (Examples 1 to 4, Comparative Examples 1 and 2) 1-1) Experimental method (1) Raw material polymer: The polymer pellets shown in Table 1 were used.

[0011]

[Table 1]

The melting point was measured with a differential scanning calorimeter (DSC) at a temperature rising rate of 10 ° C./min. (2) Preparation of sheet: The pellets of (1) are appropriately selected, melted at 190 to 220 ° C., and discharged from a single-layer type, two-kind two-layer type or two-kind three-layer type inflation die (blow-up). After being cooled with a water-cooled ring in a ratio of 1 or 2), it was wound at a speed of 5 m / min to obtain an inflation sheet having a thickness of 0.28 mm and a folding diameter of 150 mm. Table 2 shows the sheet structure. (3) Preparation of container: 240 mm of the sheet obtained in (2)
The bag was cut into a long length, and both ends were heat-sealed to form a bag, and 500 ml of physiological saline was put therein and sealed. (4) High-pressure steam sterilization test: The container containing the physiological saline solution obtained in (3) was placed in a retort type high-pressure steam sterilizer at a temperature of 1
The treatment was carried out under the conditions of 10 ° C., gauge pressure of 1.8 kg / cm ² , and time of 60 minutes. After cooling to room temperature, it was allowed to stand for another 3 days to obtain measurement samples (5) and (6). (5) Measurement of sheet physical properties: The container sheet after standing for 3 days in (4) was cut out, and the transmittance in water at a wavelength of 450 nm was measured with a Shimadzu double beam type self-recording spectrophotometer UV-300 to obtain a measure of transparency. did. The tensile modulus was measured according to JIS K7113 and used as a measure of flexibility. (6) Investigation of container (sheet) surface: In addition to visually observing the sticky state of the container surface after leaving for 3 days in (4),
I touched it and looked it up. (7) Eluent test: The sheet obtained in (2) was tested according to the Japanese Pharmacopoeia General Test Method “Plastic Container Test Method for Infusion”.

[0013]

[Table 2]

1-2) Experimental results (1) Extrusion molding of the sheet was successful, and no foreign matter, foaming, blocking, etc. were observed in any composition.
A uniform sheet was obtained. (2) It was confirmed that the eluates of the sheets of Examples 1 to 5 were compatible with the Japanese Pharmacopoeia. (3) The following is clear from the "property of the sheet (container)" in Table 2. (A) A sheet having an M-PP forming layer having a melting point of 140 ° C. or less has excellent transparency and is more flexible than the high melting point M-PP (Comparative Example 1) and ordinary PP (Comparative Example 2). It is generally said that the tensile elastic modulus of 3,000 kg / cm ² or less is sufficiently practical as a soft bag, and the sheet used for the container of the present invention satisfies this requirement. (B) The stickiness phenomenon does not occur on the surface of the container (sheet), probably due to the narrow molecular weight distribution of M-PP, and thus PP
The disadvantage of (Comparative example 2) is solved. In the case of Comparative Example 2, the surface was sticky enough to make the surface feel wet.

(Examples 5 and 6) 2-1) Experimental method (1) Preparation of multi-chamber container: The inflation sheet used in Examples 2 and 4 (corresponding to Examples 5 and 6, respectively) was used.
Cut into 0 mm length, heat-seal the width of 7 mm at the center at a temperature of 120 ° C., a pressure of 2 kg / cm ² , and a time of 5 seconds, then amino acid 3 wt / V% aqueous solution in one chamber and glucose 15 wt in the other chamber.
Put 300ml each of / V% aqueous solution, width 10mm at both ends, temperature 1
Heat sealing was performed under the conditions of 60 ° C., pressure of 4 kg / cm ² , and time of 5 seconds to prepare a multi-chamber container containing two chemical liquids. (2) High-pressure steam sterilization: The container of (1) above is placed in a high-pressure steam sterilizer and sterilized in a nitrogen atmosphere at a temperature of 110 ° C., a gauge pressure of 1.8 kg / cm ² , and a time of 30 minutes until room temperature. Cooled. (3) Measurement of seal strength: After the container of (2) above was left in a nitrogen atmosphere for 3 to 5 days, the central part (partition part) of the container
Cut off the seal part at the end and the edge (peripheral part), and
The 180 ° peel strength was measured at a speed of / minute and converted into a seal strength when the width was 15 mm (n = 3 for each example). (4) Evaluation of breakability (communicability) of the partition part of the container: The container of (2) after being left for 5 days is laid on a desk, and the partition part is pressed by one hand with one hand. It was confirmed whether or not the seal of (1) was broken (test was conducted 5 times for each example).

2-2) Experimental results (1) Seal strength: The seal strength of the partition of the container is 0.4 to 0.5 kg / 15 mm in Example 5, and 0.5 k in Example 6.
It was g / 15 mm. In addition, the sealing strength of the peripheral portion was 2.5 to 2.7 kg / 15 mm in both Examples 5 and 6. (2) Breakability (communicability) of the partition part of the container: Both Example 5 and Example 6 were good and could be easily communicated. The data on the seal strength in (1) above also support this.

[0017]

As described above, the medical container of the present invention is formed of a sheet containing M-PP having a relatively low melting point as a component of a single-layer sheet or a multi-layer sheet. It was revealed that good transparency and flexibility are exhibited even after high-pressure steam sterilization, and the problems of the conventional low melting point PP are solved. Since it is highly productive and versatile, it has a high industrial value.

Claims (1)

[Claims] 1. A medical container, which is formed of a sheet containing polypropylene as a forming layer, which is produced from a metatheron-based catalyst and has a melting point of 140 ° C. or lower.