JP3309191B2 - Medical multilayer film and multi-chamber container - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a medical multilayer film excellent in transparency, flexibility, impact resistance, easy peel sealability, and the like, and a medical multi-chamber container molded using the multilayer film. .

[0002] In the present specification, easy peel sealability means a strong seal portion which cannot be peeled and opened substantially by changing a welding temperature during heat sealing, and a weak seal portion which can be easily peeled and opened (hereinafter referred to as an easy peel seal). Part) is a property that can be selectively formed.

[0003]

2. Description of the Related Art As a conventional medical container film, a film made of polyethylene or polypropylene having high chemical stability against acids, alkalis, salts and the like is often used. In addition, as a film for a multi-chamber container for separately dividing and accommodating an unstable drug which may cause a change with time when compounded at the same time, a mixture of α-polyolefin resins having different compatibility such as polyethylene and polypropylene is melt-mixed. A single-layer or two-layer film having a modified resin layer is known.

For example, Japanese Patent Application Laid-Open No. 2-4671 discloses a single-layer film, a two-component mixed resin single-layer film of linear low-density polyethylene and polypropylene, or a linear low-density polyethylene, polypropylene and ethylene-propylene. A three-component mixed resin single-layer film with a copolymer is disclosed. As the two-layer film, a two-layer film composed of an outer layer of linear low-density polyethylene and an inner layer of a mixed resin of linear low-density polyethylene and polypropylene is disclosed.

[0005] Among the above mixed resins, polypropylene has the highest melting point and is mainly used to ensure easy peel sealability.

[0006] However, the single-layer film of the above two-component mixed resin has higher transparency and lower transparency than polyethylene in the single-layer resin.
Since a large amount of polypropylene having poor flexibility is mixed, production of a container using this film results in poor practicality in terms of transparency, flexibility and impact resistance.

Further, in the case of a single-layer film of a three-component mixed resin, there is a problem of non-uniformity of components at the time of film formation. In other words, since the fluidity of the ethylene / propylene copolymer, which is amorphous or low crystalline and has the lowest melting point, is larger than the other two components, especially compared with polypropylene, the resin component of the film is very large. May be biased, and it is difficult to make use of the excellent properties of the ethylene / propylene copolymer resin, such as transparency, flexibility, and impact resistance, in the film. In addition, it is difficult to uniformly disperse the polypropylene in the polyethylene, and it is difficult to mold a film having excellent easy peel sealability, that is, a film in which the polypropylene is uniformly dispersed. Moreover, in the single-layer film, the difference in the melting points of the component resins is large when heat sealing is performed. Therefore, when the component resin having the highest melting point (polypropylene) starts to melt, the component resin having the lowest melting point (ethylene (Propylene copolymer) melts too much and flows as a liquid, and the film thickness at the time of heat sealing becomes extremely thin (a so-called second break phenomenon). Therefore, there is also a problem that it is not possible to perform appropriate heat sealing while maintaining the strength of the container.

On the other hand, in the case of the two-layer film described in the above-mentioned publication, a linear low-density polyethylene (L-
Since LDPE) is used, the transparency and flexibility are slightly improved as compared with the case of a single layer, but are not satisfactory, and the impact resistance as a container is practically useful (particularly, container). (When the temperature is cooled to 5 ° C. or less), it is not satisfactory because of these problems, and it is difficult to say that it is suitable for practical use. Transparency and flexibility are important evaluation items because they greatly affect the handling in medical settings.

Accordingly, it is an object of the present invention to solve the above-mentioned problems and to provide a medical film and a multi-chamber container excellent in all of transparency, flexibility, impact resistance and easy peel sealability. .

[0010]

According to the present invention, two sheets are superposed.
Easy peel seals are in contact with each other when
The side formed is referred to as the inside, and is a multilayer film composed of three layers of an inner layer mainly composed of polyolefin, an intermediate layer, and an outer layer, wherein the inner layer has a density of 0.918.
g / cm3 or more and less than 0.930 g / cm3, the intermediate layer is made of a mixed resin of an ethylene / α-olefin copolymer and polypropylene, and has a density of 0.885 to 0.920 g / c.
From the ethylene / α-olefin copolymer of m ³ , the outer layer has a density of 0.918 g / cm ³ or more and 0.930 g / c
from m ³ below ethylene · alpha-olefin copolymer, are formed respectively, the density of the ethylene · alpha-olefin copolymer outer layer, than that of the intermediate layer 0.002 g / cm ³
And the mixing ratio (weight ratio) of polypropylene and ethylene / α-olefin copolymer in the inner layer is 1
The present invention relates to a medical multilayer film characterized by having pairs 1 to 3.

A preferred embodiment of the present invention is a multilayer film in which the intermediate layer is composed of a mixed resin of two or more ethylene / α-olefin copolymers.

Further, the medical multi-chamber container of the present invention is characterized by being molded using the above-mentioned multilayer film.

An embodiment of the present invention will be described below with reference to the accompanying drawings. The ethylene / α-olefin copolymer in the present invention is mainly composed of ethylene, and contains α-olefin at a certain ratio. The structure of the copolymer may be any of a random copolymer, a block copolymer and a graft copolymer.

The ethylene / α-olefin elastomer is an amorphous or low-crystalline ethylene / α-olefin copolymer.

An ethylene / α-olefin copolymer,
Or, in the ethylene / α-olefin-based elastomer, examples of the α-olefin include propylene, 1-butene, 1-pentene, 1-hexene, and 4-methyl-1-
Pentene, 1-heptene, 1-octene, 1-nonene,
Examples thereof include those having 3 to 12 carbon atoms such as 1-decene, 1-undecene, and 1-dodecene, and among them, a copolymer with 1-butene can be suitably used. In particular, it is preferable to use a linear polymer as the ethylene / α-olefin copolymer.

The medical multilayer film according to the present invention is shown in FIG.
As shown in FIG. 2, the inner layer 1, the intermediate layer 2, and the outer layer 3 are composed of three layers.

The inner layer 1 is made of a mixed resin of an ethylene / α-olefin copolymer and polypropylene in order to enable easy peel sealing. However, the inner layer 1 is used in order not to impair transparency and flexibility. The resin to be used and the configuration are as follows. That is, the ethylene / α-olefin copolymer has a density of 0.918 g / cm ³ or more,
Less than 0.930 g / cm ³ , preferably 0.918 to
Use the one with 0.925 g / cm ³ . Further, as the polypropylene, either a propylene homopolymer or a copolymer of propylene and an α-olefin can be used.

The copolymer of propylene and α-olefin is composed mainly of propylene as a comonomer, contains α-olefin at a certain ratio, and is composed of propylene random copolymer, propylene block copolymer and propylene graft copolymer. Any of coalescence may be used. Α contained in the above copolymer
-As olefins, besides ethylene, 1-butene, 1
-Pentene, 1-hexene, 4-methyl-1-pentene, 1-heptene, 1-octene, 1-nonene, 1-decene, 1-undecene, and 1-dodecene having 4 to 12 carbon atoms
And a copolymer with ethylene is preferable.

When polypropylene is a copolymer, it must have the same heat resistance as propylene homopolymer. Therefore, the mixing ratio of α-olefin to propylene is set from a relatively small range. For example, when the α-olefin is ethylene, the mixing ratio is 2
The content is set to 0% by weight or less, preferably 10% by weight or less, more preferably 5% by weight or less. Hereinafter, polypropylene includes both homopolymers and copolymers unless otherwise specified.

The melt flow rate of polypropylene (M
FR) can be selected from those of 1 to 10 g / 10 minutes (230 ° C.).

The MFR of the polypropylene is appropriately selected with respect to the MFR of the ethylene / α-olefin copolymer. For example, the MFR of the ethylene / α-olefin copolymer is about 2 g / 10 minutes (190 ° C.). For
It is preferable to use a propylene homopolymer having an MFR of 3 to 10 g / 10 minutes (230 ° C.), preferably 3 to 7 g / 10 minutes (230 ° C.). It is also preferable to use a propylene homopolymer having the same MFR as the above-mentioned ethylene / α-olefin copolymer under the same temperature conditions.

When the polypropylene is a propylene random copolymer, for example, the MFR is 1 to 10 g / 10 with respect to the ethylene / α-olefin copolymer having an MFR of about 2 g / 10 min (190 ° C.). Minutes (230
C), a propylene random copolymer such as an ethylene / propylene copolymer is preferably used.

Thus, both can be mixed almost uniformly, and a resin layer excellent in easy peel sealability can be obtained, and a resin in which the opening force of the easy peel seal portion is stable can be obtained. .

The mixing ratio (weight ratio) of the polypropylene to the ethylene / α-olefin copolymer affects the hermetic sealability and openness of the easy peel seal, and the mixing ratio (weight ratio) of the former to the latter is used. Is 1: 1 to 3, especially 1: 2, good results are obtained. By the way, if the mixing amount of polypropylene does not reach the above range, openness,
In addition, when the ratio exceeds the above range, the hermetic sealability becomes insufficient, which is not preferable. The thickness of the inner layer 1 is 10 to 50 μm
The thickness is appropriately selected, preferably from the range of 25 to 35 μm. From this thickness range, the thickness is about 15 to 38%, preferably 15 to 25% of the thickness of the entire multilayer film. It is appropriately selected.

The intermediate layer 2 has a density of 0.885 to 0.920 g / cm ³ , preferably 0.900 to 0, in order to impart transparency and impact resistance to the whole film without impairing transparency and flexibility. .920 g / cm ³ of ethylene α-
An olefin copolymer is used, and among them, a linear polymer is preferably used, and further has a density difference from the resin of the outer layer as described later. One kind of resin may be used for the intermediate layer 2, but it is preferable to use a mixture of two or more kinds of resins having different densities.
Density 0.918 to 0.925 g / c called PE
m ³ ethylene / α-olefin copolymer and a density of 0.
The mixing ratio (weight ratio) with the ethylene / α-olefin-based elastomer of 880 to 0.890 g / cm ³ is 4: 6 to
A 6: 4 mixed resin is preferred. In addition, even when a mixed resin is used, the entire density is set to be within the above range.

The thickness of the intermediate layer 2 is selected from the range of about 30 to 100 μm, preferably 65 to 95 μm, and is about 14 to 50%, preferably 40 to 50% of the total thickness of the multilayer film. Is appropriately selected so that

The outer layer 3 is required to be durable to temperature conditions and shocks such as high-pressure steam sterilization or hot water sterilization as heat sterilization in addition to transparency and flexibility. ethylene · alpha-olefin copolymer used density 0.918 g / cm ³ or more, 0.930 g / cm ³
Less than, preferably from 0.918 to 0.925 g
/ Cm ³ , and among them, a linear polymer is preferably used, and it can be obtained by further increasing the density of the resin of the intermediate layer by 0.002 g / cm ³ or more. The thickness of the outer layer 3 is from about 50 to 145 μm,
It is preferably selected from the range of 50 to 80 μm, and is about 25 to 78%, preferably 25 to 78% of the total thickness of the multilayer film.
It is selected to be in the range of ~ 45%.

The multilayer film of the present invention is produced by applying a known production method such as a water-cooled or air-cooled coextrusion inflation method, a coextrusion T-die method, and a lamination method.
In particular, co-extrusion molding is preferably performed by a co-extrusion method. In addition to forming a resin layer having a substantially uniform thickness to increase molding efficiency, the characteristics of each layer are maintained because the resin is less deteriorated during molding. Good transparency and flexibility can be obtained. The resulting multilayer film is tubular,
May be sheet-shaped. The temperature conditions in manufacturing are 16
It is 0-250 ° C, more preferably 165-230 ° C. Each of the layers 1, 2, and 3 contains an ethylene / α-olefin copolymer as a common component, and the layer 2 contains a resin having excellent melting property by heat. The layers are easily welded and delamination hardly occurs. It is desirable that the resin constituting each layer has a small difference in melt flow rate (MFR) in order to maintain a substantially uniform layer thickness and moldability. Furthermore, the multilayer film of the present invention may be co-extruded with one layer divided into two or more layers, whereby the transparency of the entire film can be further improved.

However, in this case, since it is made of the same resin, it is treated as a single layer even if it is molded in multiple layers.

According to the present invention, the transparency and flexibility possessed by each of the layers 1, 2, and 3 can impart excellent transparency and flexibility to the entire film, and the excellent transparency and flexibility of the intermediate layer 2 and the outer layer 3 can be achieved. Impact resistance and excellent easy peel sealability from the inner layer 1 can be obtained.
Therefore, according to the present invention, a medical multilayer film excellent in transparency, flexibility, impact resistance and easy peel sealability can be provided. In the multilayer film of the present invention, since the ethylene / α-olefin copolymer is used for the outer layer, for example, a cover of a barrier multilayer film (the inner layer having an ethylene / α-olefin copolymer) is provided outside the film. In the case of welding, there is an advantage that welding can be easily performed.

Further, the multilayer film of the present invention can be used for medical multi-layers which can store and mix or dissolve drugs which may change over time when mixed simultaneously in separate chambers separated by an easy peel seal or the like. A chamber container can be provided. As with the multilayer film of the present invention, the multi-chamber container is excellent in transparency, flexibility, impact resistance and easy peel sealability.

The drug enclosed in the double-chamber container may be any of a powder, a liquid and a solid. Examples of the powder include a hygroscopic property such as an antibiotic, an anticancer drug, a steroid, a thrombolytic or a vitamin. Examples of the substance are easily oxidizable and easily denatured by heat. Examples of the liquid preparation include physiological saline, glucose solution, distilled water for injection, electrolyte solution, amino acid solution, fat emulsion and the like.

When the antibiotic is stored and stored in the double-chamber container, the low-molecular-weight substance (70 or less carbon atoms, particularly 22 to 28 carbon atoms) contained in the raw material resin of the multilayer film of the present invention is used.
However, there is a possibility that insoluble fine particles may be formed by combining with an antibiotic. Therefore, it is preferable to preliminarily heat the raw resin under reduced pressure, remove low-molecular-weight substances by maintaining the reduced pressure during film molding, or extract or wash with n-hexane or hot water. .

When a multi-chamber container is manufactured using the multilayer film of the present invention, the multi-chamber container is manufactured, for example, by the following method. FIG. 2 shows an example of a method for manufacturing a multi-chamber container in the order of steps. The multi-chamber container A can be obtained by sequentially performing the following steps (a) to (e).

Step (a) —The multilayer film is cut into a predetermined size, and a hole 5 for an opening is formed in the center of the film 4.

(B) Step-On the outer layer side of the film 4, a mouth 6 is attached to the hole 5 by applying welding means.

(C) Step-The film 4 is folded around the opening 6 so that two films are superposed.

(D) Step-2: The peripheral portion of the laminated film 4 is welded at a welding temperature of 145 to 18 except for filling ports 7 and 8.
The container is sealed at 5 ° C. to form a strong seal portion 9 to form a container.

Step (e)-Easy peel seal portion (weak seal portion) 10 is welded to the intermediate portion of the container at a temperature of 105 to 13
Form at 5 ° C. to obtain a multi-chamber container A.

In the case where highly reactive chemicals are separately sealed in both chambers in the lower container part separated by the easy peel seal part 10, for example, the filling ports 7, 8 are provided in the upper and lower container parts. After filling the liquid medicines 11 and 12 through the port, both filling ports 7 and 8 are sealed, and high-pressure steam sterilization or hot water sterilization is performed. After the sterilization, the outside of the container is dried and adjusted to a predetermined shape. This state is shown in FIG.

On the other hand, in the case where a drug such as an antibiotic and a drug solution such as a solution are sealed in the upper and lower containers, FIG.
In the state of (e), the solution 1
After filling 3, both filling ports 7, 8 are sealed, and high-pressure steam sterilization or hot water sterilization is performed. This state is shown in FIG. After the sterilization is completed, the outside of the container is dried.
As shown in (g), the filling port 8 on the side of the empty room is opened again by cutting, and clean air is blown from here to dry. Then, a drug 14 such as an antibiotic is filled under aseptic conditions through the reopening filling port 8 as shown in FIG. 2 (h), and after filling, the filling port 8 is sealed as shown in FIG. 2 (i). , And the process is completed.

[0042]

EXAMPLES Examples of the production of the medical multilayer film and the multi-chamber container of the present invention will be described below, followed by test examples using the same.

[0043]

Example 1 A linear low-density polyethylene (ethylene / 1-butene copolymer) [manufactured by Mitsui Petrochemical Co., Ltd .; density 0.92 by a water-cooled co-extrusion blow molding machine.
0 g / cm ³ , MFR 2.0 g / 10 min (190 ° C.)]
(Hereinafter referred to as “PE”) and propylene homopolymer [manufactured by Mitsui Petrochemical Co., Ltd .; density 0.910 g / c
m ³ , MFR 7.0 g / 10 min (230 ° C.)] (hereinafter referred to as “PP”) in a resin mixing ratio (weight ratio) of 2: 1.
Having a mixed resin layer of 30 μm in the inner layer, comprising PE and an ethylene / α-olefin-based elastomer (ethylene / 1
-Butene copolymer) [manufactured by Mitsui Petrochemical Co., Ltd. (trade name: Tuffmer A); density: 0.885 g / cm ³ , MFR
1.0 g / 10 min (190 ° C.)] (hereinafter referred to as “PE”). The intermediate layer has a mixed resin layer 80 μm having a resin mixing ratio (weight ratio) of 1: 1 in the intermediate layer, and the PE layer 65 μm.
m was formed in the outer layer. Using the film, the sealed seal (strong seal) temperature at the peripheral portion is set to 150 ° C., the easy peel seal temperature at the intermediate portion is set to 125 ° C., and the content is 100 ml.
A multi-chamber container with an easy peel seal was manufactured.

[0044]

EXAMPLES 2 TO 4 AND COMPARATIVE EXAMPLE In the same manner as in Example 1, the following multilayer film and multi-chamber container were molded.

In the comparative test, a two-layer film having a resin composition as described in the prior art was used.

[0046]

Example 2-Inner layer: PE + PP mixed resin (mixing ratio 2: 1)-Intermediate layer: PE = linear low-density polyethylene (ethylene / 1-butene copolymer) [manufactured by Mitsui Petrochemical Co., Ltd .;
Density 0.900 g / cm ³ , MFR 1.5 g / 10 min (190 ° C)] ・ Outer layer: PE

[0047]

Example 3 • Inner layer: PE + PP mixed resin (mixing ratio 2: 1) • Intermediate layer: PE = linear low-density polyethylene (ethylene / 1-butene copolymer) [manufactured by Mitsui Petrochemical Co., Ltd .;
Density ^{0.918g / cm 3, MFR 2.2g /} 10 min (190 ° C.)] - outer layer: PE

[0048]

Example 4-Inner layer: PE + PP mixed resin (mixing ratio 2: 1) PP = propylene random copolymer (ethylene / propylene copolymer) [Mitsui Petrochemical Co., Ltd .; density 0.9
10 g / cm ³ , MFR 1.0 g / 10 min (230 ° C)] (hereinafter referred to as “PP
・ Intermediate layer: PE + PE mixed resin (mixing ratio 1: 1) ・ Outer layer: PE

[0049]

[Comparative example]

 ・ Inner layer: PE + PP mixed resin (mixing ratio 2: 1) ・ Outer layer: PE

[0050]

Test Example Using the multi-chamber containers manufactured in Examples 1 to 4 and Comparative Example, each chamber of the container was filled with 50 ml of distilled water, and
After performing a hot water sterilization treatment at 06 ° C. for 35 minutes, evaluation was performed by the following test method. Table 1 shows the results.

The transparency was evaluated by visually observing the clouding of the container and measuring the light transmittance at 450 nm.

As the flexibility, the content liquid is spontaneously discharged from a height of 60 cm at room temperature. Fluctuation of the liquid discharge speed, the size of the void after discharging the liquid from the container, and the like are visually observed. The evaluation was made at a rate.

As for impact resistance, in order to perform a drop test,
One box (length × width × height = 125 × 175 × 148 mm, weight = 140 g) is packed with 9 bags of the container whose temperature is 5 ° C. or less, and three boxes are prepared. A drop impact from the floor of 1.2 m was applied to each of the sides, sides and corners of the box 10 times, and after all three boxes were finished, the containers (27 pieces) were taken out, and liquid leakage, cracks, The presence or absence of bag breakage was visually observed. (JI
(SZ-0202 compliant) A compression test was conducted as the openness (openability) of the easy peel seal part, and a compression jig having a diameter of 100 mm was attached to a tensile compression tester Strograph MZ manufactured by Toyo Seiki Seisaku-sho, Ltd. Push at a speed of 50 mm / min,
The pressure applied to the jig when the easy peel seal was opened was measured, and the coefficient of variation of the opening force was examined. However, the initial opening force of the easy peel seal portion was set in the range of 10 to 25 kg depending on the constitution of the inner layer resin.

The coefficient of variation of the opening force relatively represents the variation of the opening force of the easy peel seal portion, and was calculated by the following equation.

Coefficient of variation of opening force = standard deviation of opening force / average value of opening force In addition, visual observation of the entire external appearance was performed to evaluate wrinkles, deformation,
The situation of the bag break was investigated.

A comprehensive evaluation was performed using the above evaluation items.

[0057]

[Table 1]

Here, ◎ indicates very good, は indicates good, Δ indicates slightly poor, and × indicates bad.

The test results (Table 1) will be described in more detail.

* About impact resistance test, Examples 1-4
No cracking was observed in all 27 of the 27 containers. In the container of the comparative example, cracks occurred in 13 bags out of 27 bags.

* Regarding the flexibility test, the amount of liquid remaining in the containers in Examples 1 to 4 was within 5%. In the container of the comparative example, the remaining liquid amount in the container was 10 to 13%.

* With respect to the transparency test, a light transmittance of 85% or more was measured in the containers of Examples 1 to 4, and particularly in Examples 1 to 2 and 4, the light transmittance was 90% or more on average. Was. The highest values of Examples 1 to 2 and 4 were measured at 92%. The container of the comparative example had an average light transmittance of 80%.

* With respect to the test for opening the easy-peel seal portion, the containers of Examples 1 to 4 and the comparative example had a coefficient of variation of the opening force of 0.0 with respect to the value established as the initial opening force.
75 to 0.188, indicating a stable opening property.

[0064]

According to the present invention, it is possible to provide a medical multilayer film having excellent transparency, flexibility, impact resistance and easy peel sealability. By using such a multilayer film, transparency and flexibility can be improved. A multi-chamber medical container having excellent heat resistance, impact resistance and easy peel sealability can be provided.

[Brief description of the drawings]

FIG. 1 is an enlarged longitudinal sectional view showing an example of the multilayer film of the present invention.

FIG. 2 is an explanatory view showing a production example of the multi-chamber container of the present invention in the order of steps.

[Explanation of symbols]

 1 inner layer 2 middle layer 3 outer layer

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-4-152950 (JP, A) JP-A-63-248633 (JP, A) JP-A-4-364850 (JP, A) JP-A-2- 255248 (JP, A) (58) Field surveyed (Int. Cl. ⁷ , DB name) A61J 1/10

Claims (3)

(57) [Claims] 1. When two sheets are overlapped, they touch each other.
The side where the easy peel seal is formed is called the inside
In other words, it is a multilayer film composed of three layers of an inner layer, an intermediate layer and an outer layer mainly composed of polyolefin, wherein the inner layer has a density of 0.918 g / cm ³ or more and 0.930 g
/ Cm ³ from a mixed resin of an ethylene / α-olefin copolymer and polypropylene, the intermediate layer is from an ethylene / α-olefin copolymer having a density of 0.885 to 0.920 g / cm ³ , and the outer layer is Density 0.918 g / cm ³ or more, 0.930 g
/ Cm ³ of the ethylene / α-olefin copolymer, and the density of the ethylene / α-olefin copolymer in the outer layer is 0.002 g / cm
^3. A medical multilayer film, wherein the mixing ratio (weight ratio) of polypropylene and ethylene / α-olefin copolymer in the inner layer is 1 to 3 by ³ or more. 2. The medical multilayer film according to claim 1, wherein the intermediate layer is composed of a mixed resin of two or more ethylene / α-olefin copolymers. 3. A multi-chamber medical container formed by using the multilayer film according to claim 1 or 2.