JPH11377A - Medical multiple chamber vessel - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a multiple chamber vessel which has proper seal strength and is excellent in safety, flexibility, transparency or the like by forming opposed two inner walls of polyethylene having mutually different density in the vessel partitioned into plural housing chambers by a weak seal of a part of opposed inner wall surfaces. SOLUTION: In the case of manufacturing a vessel partitioned into plural housing chambers by a weak seal of a part of opposed inner wall surfaces, low density polyethylene, particularly, linear low density polyethylene(LLDPE) is used as polyethylene to be used. The LLDPE is polymerized by a metallocene catalyst or the like by using (α)-olefin and the like such as butene 1, pentene-l, hexene-1,4-methylpentene-1 as a copolymerizing component. A material having mutually different density is used as the polyethylene of the opposed inner wall surfaces, but in this case, density of high density wall side LLDPE is set to 0.920 to 0.930 g/cm<3> , and low density side density is set lower by 0.005 g/cm<3> or over than the high density side.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention is suitable for storing two or more kinds of drugs in separate storage rooms separated from each other and mixing the plurality of drugs in a closed state by breaking the separating part in use. Medical multi-chamber container.

[0002]

2. Description of the Related Art In the medical field, it is very common to administer a plurality of drug components to a living body in a mixed state, but the following method is adopted depending on the combination of drug components to be mixed. For example, in the case of infusion, a solution containing an amino acid and glucose is liable to be deteriorated due to the Maillard reaction, and thus each component is often stored in a separate closed system and mixed immediately before administration to a patient. At this time, in order to perform the mixing operation aseptically (in a closed system) and to easily operate the mixing operation, a container partitioned into a plurality of storage chambers is used, and different infusion components are stored in each of the peripheral western rooms. ,
A method has been put to practical use in which a storage room partitioned immediately before use is communicated in a closed system by some means and mixed.

[0003] It is important for the compartmenting means to be capable of stably isolating component chemicals until immediately before use and to allow easy communication at the time of use (at the time of mixing). For this purpose, various forms are devised. It has been proposed. Typical examples are those that narrow the storage space with a clamp from the outside,
The storage chambers are connected by a tube exposed to the outside of the container, and the tube is narrowed by a clamp, a communication tool (so-called click tip) communicating between the storage chambers, and a seal of a partition between the storage chambers are used. One that is relatively stable and has an adhesive strength that can be easily broken at the time of mixing is used. Of these, the most operable and practical is the so-called easy-removable double-chamber container. The technical point of this type is that the sealing of the partition wall in the storage space is relatively stable and difficult to break during manufacturing or transportation, and is easily broken by hand or jig when used (at mixing). Strong and outside (atmosphere)
And the breaking strength of the boundary part connected to it is sufficient.
Therefore, it is important to select a material for forming the inner wall of the container (that is, for forming the seal portion). In general, a material for forming the micro-layer separation structure is selected.

An example of this proposal is disclosed in Japanese Patent Application Laid-Open No. 2-4671.
JP-A-5-31153, JP-A-7-13624, etc., such as a mixture (composition) of polyethylene and polypropylene, and a mixture of polyethylene and cross-linked polyethylene (these cause cohesive failure when the seal portion is broken. Is a type). However, the problem is whether or not these materials satisfy the basic requirements for a drug container, particularly a material for an infusion container, that is, safety, flexibility, transparency, and the like, and whether there is no obstacle to production. The mixture of polyethylene and crosslinked polyethylene as described above tends to generate gels and fish eyes, is inferior in productivity, and impairs the quality and appearance of the container (product). Also,
However, although polyolefins are used, they are originally a combination of polymers having poor compatibility and different refractive indices, resulting in insufficient transparency. The easy peelable property is, of course, preferably a poorly compatible combination, but essentially contains an element that easily causes such a problem.

[0005] It is only necessary that a polymer having no microphase-separated structure, that is, a combination of polymers having high compatibility can exhibit easy-repeatable properties. A typical example is a mixture of two or more polyethylenes having different densities as disclosed in JP-A-8-229101. But,
When I actually try it, it is difficult to balance easy repeatability with transparency. In other words, the larger the difference in density between polyethylene, the more easily it becomes easy to peel, but it is necessary to include relatively high-density polyethylene (because the higher the density of polyethylene, the lower the transparency). However, it is pointed out that the transparency of the container (product) is necessarily inferior.

[0006]

SUMMARY OF THE INVENTION The present invention has been made to solve the above-mentioned problem in the conventional easy peelable type multi-compartment container, that is, the imbalance between easy peelable property and transparency.

[0007]

SUMMARY OF THE INVENTION The gist of the present invention is to provide a container which is divided into a plurality of storage chambers by a weak seal on a part of the opposing inner wall, and the two opposing inner walls are mutually dense. Is a multi-chamber medical container made of polyethylene of different types, has an appropriate sealing strength, safety, flexibility,
Provide a multi-chamber container with excellent transparency and appearance. The point of the present invention is that the densities of the polyethylene on the opposite inner wall surfaces are different, that is, the melting points or the crystallinity are different, and the two walls having different melting and crystallization behaviors are sealed. (Weak seal)
Is characterized by being easily formed stably.

[0008] The polyethylene in the present invention is generally known, but from the viewpoint of the transparency and flexibility of the container which is the purpose of the present invention, low density polyethylene, particularly linear low density polyethylene (LLDPE) is suitable for the purpose. ing. LL
As is well known in the DPE, butene-1, pentene-1, hexene-1, 4-methylpentene-1, heptene-1,
Α-olefins such as octene-1, decene-1 and dodecene-1 are used as copolymerization components and polymerized by a Ziegler-Natta catalyst or a metallocene catalyst. In consideration of transparency, flexibility or sealing property, the density is 0.905 to 0.905.
0.935 g / cm ^3, more preferably 0.910
0.930 g / cm ³ is preferred. The container of the present invention is characterized in that the densities of polyethylene on the inner wall surfaces facing each other are different, but it is preferable to combine the above LLDPE. It is most recommended that the density of the LLDPE on the high-density wall side is 0.920 to 0.930 g / cm ³ , and the density of the LLDPE on the low-density side is 0.005 g / cm ³ than that on the high-density side.
than cm ³ or more preferably less combined 0.007 g / cm ³ or more.

In the container of the present invention, the configuration of the inner wall surface only needs to satisfy the above conditions, and the sheet forming the wall itself may have a multilayer (multi-layer) structure. is there. Multilayering is generally applied to improve the strength, transparency, flexibility, heat resistance and the like of the sheet. The polymer or polymer composition constituting the intermediate layer or the outer layer in the case of a multilayer is as follows: (a) LLDPE: those having a density of 0.900 to 0.930, more preferably 0.905 to 0.925 g / cm ^3. Good. (B) Crystalline polypropylene or a crystalline copolymer comprising the same. However, it is preferable to use it as a thin layer because of its high rigidity. (C) A polymer composition of (b) and an olefin-based thermoplastic elastomer or a styrene-based thermoplastic elastomer. Typical olefin-based thermoplastic elastomers are ethylene propylene copolymer and ethylene butene-1 copolymer, and styrene-based thermoplastic elastomers include block (polystyrene-ethylenebutylene copolymer-polystyrene) (SEBS) and block (polystyrene-ethylenepropylene). Copolymer-polystyrene) (SEPS) is a representative example. These thermoplastic elastomers should account for 10 to 50% by weight, more preferably 15 to 40% by weight, of the polymer composition.
(D) Crystalline polyten-1 or a crystalline copolymer containing the same as a main component.

The thickness of the sheet forming the multi-chamber medical container of the present invention is suitably from 0.08 to 0.6 mm, more preferably from 0.1 to 0.5 mm. The thickness of the inner wall layer is preferably at least 0.01 mm, more preferably at least 0.02 mm. The double-chamber container of the present invention is usually manufactured by a known method. That is, it is extruded through a single-layer or multilayer T-die or circular die (the melting temperature is preferably 160 to 230 ° C., and more preferably 170 to 210 ° C.), and the obtained flat sheet or tube is obtained. The sheet, parison, etc. may be processed into a predetermined shape and form by appropriately utilizing techniques such as blowing, stretching (no stretching is preferable in consideration of heat sealing properties), cutting, and fusion. It is also possible to obtain sheets having polyethylene portions having different densities at once. In this case, a separator is provided inside the die as described in JP-B-52-10142 and JP-A-57-103833. A scheme can be applied.

In the container of the present invention, the polyethylene sheet on the high-density side and the polyethylene sheet on the low-density side face each other. The most important point is the heat sealing step. In other words, the seals at the partitions (partition walls) of the plurality of storage spaces are unlikely to break during production or transportation, and have a seal strength that can be easily broken by hand, jig, or the like during use (drug mixing). (In general, the 180 ° peel strength is about 0.3 to 1 kg / 15 mm), and the seal (peripheral seal) at the portion in contact with the outside world is such that the seal (peripheral seal) cannot be easily broken (180 ° peel strength is 1.5 Kg).
g / 15 mm or more, and more preferably 2 kg / 15 mm or more), and it is important to control the conditions of the partition seal and the peripheral seal. In the case of the container of the present invention, the partition seal is at a temperature of 100 to 130 ° C.,
Pressure 1 to 4 kg / cm2, time 0.2 to 5 seconds, seal width 2 to 10 mm, peripheral seal temperature 120 to 180 ° C, pressure 2 to 5 kg / cm2, time 0.2 to 10 seconds, seal width 5 mm or more It is usually performed under conditions. The number of accommodation rooms is generally two to four.

It should be noted that, within a range not to impair the gist of the present invention,
About 5 to 20% by weight of ethylene propylene copolymer, ethylene butene-1 copolymer, SEBE, SEPS, or the like may be added to either one of the polyethylene forming the inner wall layer. The double-chamber container of the present invention
When the drugs are liquids (for example, a combination of an amino acid solution and a glucose solution), one of the drugs is a liquid and the other is a solid (for example, a combination of a saline solution and an antibiotic).

[0013]

The present invention will be described more specifically with reference to the following examples. (1) Experimental method Preparation of raw polymer: used raw polymer (Ziegle
Table 1 shows r-natta catalyst system LLDPE).

[0014]

[Table 1]

Sheet adjustment: LLDP of Tables A to D
E was melted with a single screw extruder (temperature 1
80-190 ° C), discharged into a sheet through a T-die, cooled with a casting roller maintained at 20 ° C, trimmed, and wound at a speed of 6 m / min into a sheet having a thickness of 0.25 mm and a width of 210 mm. I took it. Production of double-chamber container: The sheet produced in the above was cut into a length of 300 mm. Next, by appropriately combining the types of the two sheets, a width of 7 mm at the central portion is adjusted to a temperature of 100 to 130 ° C., a pressure of 2 kg / cm ² , a time of 5 seconds, and a width of 8 at the peripheral portion (side portion).
After heat sealing under the conditions of a temperature of 150 ° C., a pressure of 2 kg / cm ² , and a time of 2 seconds, 400 ml of a 3 wt / V% aqueous solution of amino acid and 400 ml of a 15 wt / v% aqueous solution of glucose are put in one chamber and the other end. 10 mm width at 150
Heat sealing was carried out at a temperature of 2 ° C., a pressure of 2 kg / cm ² , and a time of 2 seconds to prepare a multi-chamber container with two compartments. High-pressure steam sterilization: Put the container in the above-mentioned high-pressure sterilizer, in a nitrogen atmosphere, at a temperature of 107 ° C. and a gauge pressure of 1.8 kg / c.
The solution was sterilized under the conditions of m ² for 30 minutes and cooled to room temperature.

Evaluation of Transparency of Container: The container was allowed to stand in a nitrogen atmosphere at room temperature (20 to 25 ° C.) for 48 hours or more.
The transmittance in water at nm was measured with a Shimadzu double beam type self-recording spectrophotometer UV-300, and was used as a measure of transparency. Evaluation of flexibility of container: The sheet of the container was cut into a dumbbell shape, and the tensile elastic modulus was measured according to JIS K7113 to obtain a measure of the flexibility. Measurement of seal strength: Cut off the seal part at the center part (partition part) and the peripheral part (side part) of the container.
The 180 ° peel strength was measured at a speed of mm / min (the peel strength in Table 2 is a value converted to a 15 mm width). Evaluation of Breakability (Communication) of Partitioning Part of Container: The container was placed on a desk, and it was confirmed whether or not the seal of the partitioning part could be broken only by pressing one compartment side by hand. Dissolution test: Each sheet was subjected to a dissolution test according to the Japanese Pharmacopoeia (13th revision) general test method "Plastic drug container test method".

(2) Experimental results

[0018]

[Table 2]

As is evident from Table 2, the transparency and flexibility of the container sheet both show sufficient properties as an infusion container. What is important as a multi-chamber container is that the appropriate temperature of the "partition seal" is wide. The appropriate temperature shown in Table 2 is a sealing temperature range in which a suitable easy-repeatable property is given to the partition portion (that is, at a sealing temperature higher than this range, the easy-peelable property is not exhibited; Even if it is held down by hand, the partition portion is not easily broken, and if the temperature is lower than this range, the sealing strength is too low, so that a stable partition is not formed). It has a width of about 10 ° C and has a wide range of temperature control. On the other hand, in the case where the partition portion is formed of sheets having the same density as in Comparative Examples 1 and 2, the appropriate temperature is only in the range of about 3 ° C., and strict temperature control is required. Production would be difficult. Regarding the peripheral seal, any diameter shows stable strength, and there is no problem. In addition, it has been confirmed that the results of the “eluate test” all meet the standards.

[0020]

As described above, the present invention is an application of the dissolution behavior when sealing polyethylene sheets having different densities to a multi-chamber container, and the performance (easy peelable property) as a multi-chamber container is as follows. Of course, transparency and flexibility are sufficient.

Claims (2)

[Claims] 1. A container which is divided into a plurality of storage chambers by a weak seal at a part of an inner wall surface facing each other, wherein said two inner wall surfaces are made of polyethylene having different densities from each other. Medical dual chamber container. 2. The two polyethylenes forming opposite inner walls are linear low-density polyethylene, the density of polyethylene on the high-density wall side is 0.920 to 0.930 g / cm ³ , and the density on the low-density side is Is 0.005g / c from the high density side
multi-chamber medical container according to claim 1, characterized in that m ³ or more low.