JPH08229099A - Medical double-chamber container - Google Patents

Abstract

PURPOSE: To resolve such problems as the safety, flexibility, transparency, and pressure steam sterilization of a material by forming the inner wall face of a medical double-chamber container with a polymer composition material of polyethylene and a specific block copolymer. CONSTITUTION: When this medical double-chamber container 1 is to be used, storage chambers 5 are pressed by a hand or an apparatus, then an adhesive section 4 is peeled, two storage chambers 5 are communicated, and separated medical liquids can be mixed. The inner wall face of the medical double- chamber container 1 is made of a polymer composition material of polyethylene and at least one block copolymer selected from a group of the block (polyethylene-ethylene butylene copolymer-polyethylene), block (polyethylene- ethylene propylene copolymer-polyethylene), block (polystyrene-ethylene butylene copolymer-polyethylene), and block (polystyrene-ethylene propylene copolymer- polyethylene).

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention stores two or more kinds of medicinal liquids in separate storage chambers separated by an adhesive portion, and separates the adhesive portions at the time of use to seal the plural medicinal liquids in a sealed state. A medical multi-chamber container suitable for mixing.

[0002]

2. Description of the Related Art In the medical field, it is very common to administer a mixture of a plurality of drug components into a living body.
The following methods are adopted depending on the combination of the drug components to be mixed. For example, in the case of infusion, a liquid containing amino acid and glucose is likely to be deteriorated by the Maillard reaction, so that 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 (in a 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. Incidentally, a method has been put into practical use in which the storage chambers partitioned just before use are made to communicate with each other in a closed system by some means and mixed.

As a means for partitioning the storage chamber, it is important to be able to stably isolate the component infusion liquid just before use and to allow easy communication during use (mixing). For this purpose, various forms are devised. Has been proposed. A typical example is one in which the space between the storage chambers is clamped from the outside by a clamp (Japanese Patent Laid-Open No. Sho 53)
No. 38189, JP-A No. 61-103823, JP-A No. 1-160558, etc., in which the storage chambers are connected by a tube exposed to the outside of the container, and the tube is clamped by a clamp (Shokai 57-57). 76636), etc., having a communication tool that can communicate between the storage chambers when in use (JP-A-57-52)
No. 455, etc.), and an adhesive part for partitioning the storage chambers is a seal having a sealing strength that is relatively stable and can be easily peeled off during mixing (Japanese Patent Publication No. 6-26563, JP-A-63-309263, Japanese Patent Laid-Open No. 1-240469,
(JP-A-2-4671, JP-A-2-57584, JP-A-2-241457, JP-A-2-255418, JP-A-4-242647, JP-A-5-31153, JP-A-5-68702). Is. Among them, the one having a high operability and a practicality is a so-called easy-peelable multi-chamber container, which has been receiving the most attention. The technical point of this type is that the peelable adhesive part between the storage chambers is relatively stable during manufacturing or transportation and is difficult to peel off, and it can be easily peeled off by hand or equipment during use (mixing). Has sufficient sealing strength and is in the external environment (atmosphere)
That is, the sealing strength of the peripheral portion connected with is sufficient. Therefore, the selection of the material forming the inner wall of the container (that is, forming the adhesive portion) is most important, but generally, the material forming the micro layer separation structure, for example, a mixture of polyethylene and polypropylene, polyethylene A mixture with cross-linked polyethylene or the like (these are types in which the peelable adhesive part causes so-called cohesive peeling at the time of peeling) is used. However, the problem is that these materials are required to be infusion containers, that is, safety,
Whether or not flexibility, transparency, heat resistance (high-pressure steam sterilization resistance), etc. are satisfied and there is no hindrance to production. For example, a mixture of polyethylene and polypropylene is not sufficiently transparent, and a mixture of polyethylene and cross-linked polyethylene is liable to cause gels and fisheyes, resulting in poor productivity.

[0004]

DISCLOSURE OF THE INVENTION The present invention is directed to the safety, flexibility, and safety of the materials inherent in an easily peelable multi-chamber medical container.
The problem was to solve problems such as transparency and heat resistance (high pressure steam sterilization resistance).

[0005]

Means for Solving the Problems What has been clarified by the study by the present inventor is that a medical multi-chamber container having an inner wall surface of a polymer composition of polyethylene and a specific block copolymer solves the above problems. Is to bring. That is, it is a multi-chamber medical container as described in (1) to (3) below.

(1) A multi-chamber medical container in which opposing inner wall surfaces are partitioned by a peelable adhesive section and divided into a plurality of storage chambers, wherein the inner wall surfaces are polyethylene and a block (polyethylene- Ethylene butylene copolymer-polyethylene), block (polyethylene-ethylene propylene copolymer-polyethylene), block (polystyrene-ethylene butylene copolymer-polyethylene) and at least one block copolymer selected from the group of (polystyrene-ethylene propylene copolymer-polyethylene) A multi-chamber medical container comprising the polymer composition of

(2) The polyethylene has a density of 0.91
The multi-chamber medical container according to (1) above, which is a linear low-density polyethylene of 5 to 0.928 g / cm ³ .

(3) The weight ratio of the polyethylene and the block copolymer in the polymer composition is 85:15.
The multi-chamber medical container according to the above (1) or (2), wherein the ratio is ˜50: 50.

[0009]

EXAMPLES The form of the multi-chamber medical container of the present invention is not particularly limited, but an example of the form will be described with reference to FIGS. 1 and 2. FIG. 1 is a front view of a multi-chamber medical container,
2 is a sectional view taken along the line AA of FIG. Medical multi-chamber container 1
Is a container provided with the discharge port 2 on one side and having two storage chambers. The peripheral edge portion 3 is heat-sealed to release both ends of the inflation sheet, and the adhesive portion 4 is sealed to a peelable degree. At the time of use (during mixing), by pressing the storage chamber 5 with a hand or an instrument, the adhesive portion 4 is peeled off, and the two storage chambers 5 communicate with each other, so that the separated medicinal liquid can be easily Can be mixed. The medical multi-chamber container 1 of the present invention is
It has an appropriate sealing strength, has excellent properties such as safety, flexibility, transparency, and heat resistance, and is easy to produce.

There is room for elucidation as to whether the polymer composition of polyethylene and a specific block copolymer in the present invention forms a micro-layer separation structure or is a completely compatible system. It is believed that moderate intermolecular interactions with the copolymer are closely linked to the degree of seal strength.

In the present invention, polyethylene can be selected from commonly known high-density polyethylene (hereinafter referred to as HDPE), high-pressure low-density polyethylene (hereinafter referred to as LDPE), linear low-density polyethylene (hereinafter referred to as LLDPE), and the like. However, the proper sealing strength, which is the gist of the present invention,
In order to develop properties such as safety, flexibility, transparency, and heat resistance, a small amount (preferably 2 to 20 mol%, more preferably 3 to 15 mol%) of propylene, butene-1,
L containing α-olefins such as pentene-1, hexene-1, heptene-1, octene-1, decene-1, dodecene-1, 4-methylpentene-1 as a copolymerization component
LDPE has a density of 0.915 to 0.928 g / cm
³ is the best. If the density is lower than this range, easy peelability tends to be difficult to develop (that is, the strength of the peelable adhesive part during high pressure steam sterilization tends to be high and peeling tends to be difficult), and conversely it is transparent in the high density area. This is because there is a decrease in sex and flexibility. In addition, HDPE and L
DPE should be used when you want to control the heat resistance and flexibility of LLDPE. In consideration of moldability and mechanical properties, these polyethylenes have a temperature of 190
MFR (melt flow rate, JIS K7210) at a temperature of 2160 g at ℃ is preferably 0.1 to 1
5, more preferably 0.5-10.

Next, the block copolymer in the present invention will be described. In addition, MFR is JIS standard K721.
According to 0, it is a measured value at a temperature of 230 ° C. and a load of 2160 g.

EEBE: block (polyethylene-
Ethylene butylene copolymer-polyethylene) EEBE is poly-1,4-butadiene-polybutadiene (copolymer of 1,2-bond and 1,4-bond)
It is obtained by hydrogenating a triblock copolymer having the structure of poly-1,4-butadiene. Considering moldability and mechanical properties, polyethylene part (E part) on both ends
Is preferably 5 to 90% by weight in EEBE, more preferably 10 to 85% by weight, and the ethylene butylene copolymer part (EB part) has a butylene part ratio of 30.
Is preferably 90 to 90% by weight, more preferably 35 to 85
It is preferable that it is wt%. The MFR is 0.5 to 20.
Those of 1 to 15 are more preferable, and those of 1 to 15 are more preferable.

EEPE: Block (Polyethylene-
Ethylene propylene copolymer-polyethylene) EEPE is similar to EEBE, poly-1,
It is a block copolymer obtained by hydrogenating a triblock type copolymer having a structure of 4-butadiene-polyisoprene-poly-1,4-butadiene. Considering the same matters as in EEBE, it is preferable that the total of polyethylene parts (E parts) at both ends occupy 5 to 90% by weight in EEPE, and more preferably 10 to 85% by weight. Is preferably 0.5 to 20, more preferably 1 to 15.

SEBE: Block (Polystyrene-
Ethylene Butylene Copolymer-Polyethylene) SEBE is polyethylene-polybutadiene (1,2-
Copolymer of conjugate and 1,4-conjugate) -poly-1,
It is obtained by hydrogenating a triblock copolymer having a 4-butadiene structure. Considering the same matters as in EEBE, the weight ratio of the polystyrene part (S part), the ethylene butylene copolymer part (EB part) and the polyethylene part (E part) is preferably 3 to 30% by weight: 40 to 80% by weight: 10 to 40% by weight, more preferably 5 to 25% by weight: 45 to 75% by weight: 12 to 35% by weight. The amount of butylene in the EB part is 30 to 9
It is preferably 0% by weight. Further, the MFR is preferably about the same as EEBE.

SEPE: Block (Polystyrene-
Ethylene propylene copolymer-polyethylene) SEPE is obtained by hydrogenating a triblock copolymer having a structure of polystyrene-poly-1,4-isoprene-poly-1,4-butadiene. Considering the same matters as in EEBE, the weight ratio of the polystyrene part (S part), the ethylene-propylene copolymer part (EP part) and the polyethylene part (E part) is preferably 3 to 30% by weight: 40 to 80% by weight: 10 to 40% by weight, more preferably 5 to 25% by weight: 45 to 75% by weight: 12 to 35% by weight, and MFR is EE.
The same as BE is preferable.

The inner wall surface of the multi-chamber medical container of the present invention is formed by a polymer composition of polyethylene and the block copolymers (1) to (3) as described at the beginning, and generally, the polymer is used. The composition has heat sealability, flexibility,
Considering transparency, heat resistance, etc., the weight ratio of polyethylene to the block copolymer is preferably 85:15 to 50:50, more preferably 8:
2:18 to 60 to 40. It should be noted that if the block copolymer is too small, the easy peeling property may not be sufficient, and if it is too large, the sheet forming ability tends to be low.

The medical multi-chamber container of the present invention is a polymer composition having an inner wall surface of polyethylene and the block copolymer of (1), and (1) a polymer composition of polyethylene and the block copolymer of (1). In the case of using the sheet alone, (2) the polymer composition of polyethylene and the block copolymer of the above-mentioned to the inner layer (the inner surface of the container) and the other polymer (or the polymer composition) to the outer layer or the intermediate layer. It may be a multilayer sheet. In (2), it is combined with other polymer (or other polymer composition) depending on the required properties such as gas barrier property (water vapor, oxygen, etc.) barrier property, transparency, flexibility, heat resistance and strength. Is a specifically preferred other polymer (or other polymer composition)
A typical example of is shown below.

(A) Density of 0.910 containing α-olefins such as butene-1, pentene-1, hexene-1, octene-1, 4-methylpentene-1 as a copolymerization component.
-0.930 g / cm ³ linear low density polyethylene (L
LDPE).

(B) Crystalline polypropylene or a crystalline polypropylene-based copolymer containing the crystalline polypropylene as a main component. However, since it has high rigidity, it is preferable to use it as a thin layer.

(C) A polymer composition of (b) and amorphous polypropylene (atactic polypropylene).

(D) (b) and styrene thermoplastic elastomer (block (polystyrene-ethylene butylene copolymer-polyethylene), block (polystyrene-ethylene propylene copolymer-polyethylene), block (polystyrene-ethylene butylene copolymer-)
Polystyrene), a polymer composition with a block (polystyrene-ethylene propylene copolymer-polystyrene, etc.).

(E) Ethylene vinyl alcohol copolymer. It is used for the purpose of imparting gas barrier properties to the container.

The total thickness of the sheet forming the medical multi-chamber container of the present invention is preferably 0.2 to 0.6 mm, more preferably 0.25 to 0.5 mm. In the case of a multi-layer (case (2) above), the polymer composition layer of polyethylene and the block copolymer (1) above is preferably 0.01 mm or more, more preferably 0.02 mm or more.

The medical multi-chamber container of the present invention can be manufactured by a generally known method. That is, T for single layer or multiple layers
Extrusion through a die or circular die (melting temperature is preferably 160 to 230 ° C., more preferably 17
(0 to 200 ° C.), the obtained flat sheet, tubular sheet, parison, etc., methods such as thermoforming, blowing, stretching (non-stretching is preferable in consideration of heat sealability), cutting, and fusion bonding. It may be processed into a predetermined shape and form by appropriately utilizing. The most important point in manufacturing a medical multi-chamber container is a heat sealing process. In other words, the peelable adhesive part that divides the storage space into multiple storage spaces does not easily peel during manufacturing or transportation, and can be easily pressed by pressing the storage chamber with your hand or instrument during use (mixing). The seal strength is such that peeling is possible (generally, 180 ° peeling strength is about 0.3 to 1.2 Kg / 15 mm), and the peripheral edge that is in contact with the outside is not easily peelable (180 ° peeling Since the strength is preferably 1.5 Kg / 15 mm or more, more preferably 2 Kg / 15 mm or more),
It is important to control the condition of each seal at the adhesive and the peripheral edge. In the case of the medical multi-chamber container of the present invention, the peelable seal of the adhesive portion has a temperature of 90 to 120 ° C. and a pressure of 1
-4 Kg / cm ² , time 0.2-5 seconds, seal width 2-1
0 mm, the peripheral seal has a temperature of 120 to 160 ° C.,
Usually, the pressure is ^{2 to} 5 Kg / cm ² , the time is 0.2 to 10 seconds, and the seal width is 5 mm or more. The number of accommodation rooms is 2
Four is common.

The polymer composition of polyethylene and the block copolymers (1) to (3) above can be adjusted by using a generally known uniaxial or biaxial melt mixing extruder or static melt mixer. The melting temperature during mixing is 140-
The range of 200 ° C. is preferred.

In the range that does not impair the gist of the present invention,
Other olefinic elastomers (eg ethylene propylene copolymer, ethylene butylene copolymer, ethylene vinyl acetate copolymer, ethylene acrylic acid copolymer, etc.) may be added to the polymer composition of polyethylene and the above block copolymer. Also, to prevent blocking between sheets,
It is also possible to roughen the inner or outer surface of the container and to add an anti-blocking agent or a sleeve agent.

The multi-chamber medical container of the present invention is effective for a combination of drugs which are likely to be altered during mixing, such as a combination of an amino acid solution and a glucose solution, and can be applied not only to infusion but also to the field of blood.

The medical multi-chamber container of the present invention is described below.
This will be described in more detail with reference to specific examples.

[Materials and Method of Experiment] Examples 1 to 7, Comparative Example 1 (1) Preparation of Raw Material Polymer: The raw material polymer (pellet form) used is shown in Table 1.

[Table 1] (2) Preparation of polymer composition: Polyethylene (A1 in Table 1
~ A4), block copolymers (B1 to B4) and polypropylene (C) as raw materials, and kneaded at a predetermined ratio in a temperature range of 160 to 190 ° C using a φ45 mm biaxial melt kneading extruder and extruded. The strand was cooled with water, cut and dried to obtain a polymer composition in pellet form shown in Table 2.

[Table 2] (3) Production of sheet: The polymer or polymer composition of Table 1 and / or Table 2 is supplied to a single-layer or multi-layer circular die (inflation die), and the temperature is 180 to 190 ° C.
Extrude a tubular sheet with, cool with a water cooling ring,
A sheet having a thickness of 0.33 mm and a folded diameter of 200 mm was wound at a speed of 5 m / min.

(4) Preparation of multi-chamber medical container: The sheet obtained in (3) was cut into a length of 300 mm, the central width of 7 mm, the temperature was 115 ° C., the pressure was 2 Kg / cm ² , and the time was 5 seconds. After heat-sealing to form an adhesive part, one chamber contains 3 wt / v% amino acid aqueous solution, and the other chamber contains 15 wt% glucose.
/ V% aqueous solution (400 ml each), the peripheral edge (both ends) width 10 mm, temperature 140 ° C., pressure 4 Kg / cm ² , time 5
Heat-sealing was performed under the condition of 2 seconds to prepare a medical multi-chamber container 1 containing two drug solutions having two storage chambers 5 shown in FIG.

(5) High-pressure steam sterilization: The container of (4) was 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, Cooled to room temperature.

(6) Evaluation of container transparency: After leaving the container of (5) in a nitrogen atmosphere for 48 hours, a part of the container sheet was cut off, and the transmittance in water at a wavelength of 450 mm was measured by Shimadzu double beam type. It was measured with a self-recording spectrophotometer UV-300 and used as a measure of transparency.

(7) Evaluation of container flexibility: The sheet of the container of (5) was cut into a dumbbell shape, and the tensile elastic modulus was measured according to JIS K7113, and used as a measure of flexibility.

(8) Measurement of seal strength: The adhesive portion and the peripheral portion of the container in (5) were cut off and the 180 ° peel strength was measured at a speed of 300 mm / min (the peel strength in Table 3 was 15 mm in width. It is a converted value).

(9) Evaluation of peelability (communication) of the adhesive portion of the container: The container of (5) is laid on a desk, and the adhesive portion is peeled by pressing one accommodation chamber side by hand. It was confirmed whether or not to do it (tested 5 times for each example).

(10) Heavy metal and eluate test: According to the Japanese Pharmacopoeia General Test Method "Plastic Test Method for Infusion",
The sheet obtained in (3) was tested.

[Experimental Results] Preparation of the polymer composition and extrusion molding of the sheet were successful, and no foreign matter or foaming was observed. Polymer pellets and sheets having a high degree of uniformity were obtained in each case. .

It was confirmed that the heavy metals and the eluates were compatible with the Japanese Pharmacopoeia in any of the compositions.

Table 3 shows the constitution of the sheet and the transparency (permeability in water), flexibility (tensile modulus) and seal strength after high-pressure steam sterilization. It can be seen that all the containers (Examples 1 to 7) using the polymer composition of the present invention are excellent in transparency and flexibility. On the other hand, it is obvious that the combination of polyethylene and polypropylene (Comparative Example 1) is inferior in transparency and flexibility.

The peelability (communication property) of the adhesive portion of the container was good (including the comparative example), and it was possible to communicate easily (the sealing strength in Table 3 also confirms this).

[Table 3]

INDUSTRIAL APPLICABILITY The medical multi-chamber container of the present invention is a polymer in which a suitable compatibility between polyethylene and at least one block copolymer selected from the group of EEBE, EEPE, SEBS and SEPS is maximized. Since it contains the composition as the inner wall surface, it has good transparency and flexibility. Further, since the adhesive portion is peelable but has an appropriate seal strength, the medical liquids isolated in the plurality of storage chambers are not mixed during transportation, but can be easily mixed during use. Furthermore, it has good moldability, productivity, and heat resistance, and also meets the standards of the Japanese Pharmacopoeia regarding heavy metals and eluates, and is therefore useful as a multi-chamber container for medical use. The above characteristics show that polyethylene has a density of 0.915 to 0.928 g / c.
It is prominent when it is a linear low-density polyethylene of m ³ and when the weight ratio of polyethylene to the block copolymer in the polymer composition is 85:15 to 50:50.

[Brief description of drawings]

FIG. 1 is a front view showing an embodiment of a multi-chamber medical container according to the present invention.

FIG. 2 is a sectional view taken along line AA of the same embodiment.

[Explanation of Codes] 1 Medical multi-chamber container 2 Discharge port 3 Peripheral part 4 Adhesive part 5 Storage chamber

Claims (3)

[Claims] 1. A multi-chamber medical container in which opposing inner wall surfaces are partitioned by a peelable adhesive part and divided into a plurality of storage chambers, wherein the inner wall surfaces are polyethylene and a block (polyethylene-ethylene). Butylene copolymer-polyethylene), block (polyethylene-ethylene propylene copolymer-polyethylene), block (polystyrene-ethylene butylene copolymer-polyethylene)
And a polymer composition with at least one block copolymer selected from the group of block (polystyrene-ethylene propylene copolymer-polyethylene). 2. The polyethylene having a density of 0.915 to
The medical multi-chamber container according to claim 1, which is a linear low-density polyethylene of 0.928 g / cm ³ . 3. The weight ratio in the polymer composition of the polyethylene and the block copolymer is 85: 15-5.
The multi-chamber medical container according to claim 1 or 2, which is 0:50.