JPH09109341A - Multi-layer film and container - Google Patents

Abstract

(57) [PROBLEMS] To provide a multilayer film and a container which have excellent transparency, heat resistance, strength and flexibility and in which a lipophilic substance does not exude. SOLUTION: In a multi-layer film having a four-layer structure using an ethylene / α-olefin copolymer, the density of the resin constituting each layer is in order of the first layer: 0.935 to 0.950 g / cm ³ second layer. : 0.885 to 0.920 g / cm ³ Third layer: 0.930 to 0.950 g / cm ³ Fourth layer: 0.925 to 0.940 g / cm ³ and the resin density of the third layer is The container 1 is formed by setting it to be larger than four layers, and using the first layer as an outer layer of the container and the fourth layer as an inner layer of the container.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a multilayer film and a container molded using the same, and more specifically,
In particular, it relates to films and containers used to contain liquid drugs containing lipophilic substances, such as fat emulsions.

[0002]

2. Description of the Related Art A fat emulsion, which is an oil-in-water emulsion formulation used for the administration of high-calorie lipids, prevents essential fatty acid deficiency caused by administration of high-calorie infusions, and administers infusions from peripheral veins at a limited dose. It is an indispensable drug in the medical field to supplement nutrients from the vein, such as supplementing the amount of energy that can be supplemented immediately. In addition, certain steroids and the like may be used as a fat emulsion prepared by incorporating a drug into emulsified particles of fat for the purpose of selectively and intensively acting on the affected area.

Conventionally, the above-mentioned fat emulsion is contained in a glass container such as a glass vial or a glass ampoule in order to maintain stability. However, glass containers generally have drawbacks such as being easily damaged by dropping, being heavy, and having to be sorted and discarded. In particular, as a container for containing a large amount of drug such as an infusion solution, the glass container is notable for the above-mentioned drawbacks, and in addition, there is a problem that contamination may occur due to the need for an air needle for instillation of the drug.

Accordingly, flexible plastic containers (bags) have been replaced by containers for electrolyte infusions, sugar infusions, etc., and high-calorie infusion basic liquids and amino acid infusions are now mainly in plastic bags. Is becoming.

[0005]

In accordance with the above trends, attempts have recently been made to store a fat emulsion in a plastic bag. However, when the fat emulsion is stored in a normal plastic bag, (a) the oxygen that permeates the bag oxidizes the fat emulsion, or (b) the fat gradually permeates the plastic bag and exudes to the outer wall of the container. Such a problem occurs.

The problem (a) can be solved by means such as using an oxygen scavenger and carrying out secondary packaging with an outer bag, but in order to solve the problem (b), It becomes necessary to consider the material itself. On the other hand, as a container for a fat emulsion, the following has been conventionally proposed. (1) JP-A-3-187853 A plastic container in which at least a part of the inner surface of the container is hydrophilized to prevent the emulsion emulsion from breaking. (2) JP-A-5-31154 A container using a multilayer film in which saponified ethylene-vinyl acetate copolymer or polyamide is arranged in an intermediate layer, wherein ethylene-propylene random copolymer is contained in the inner layer of the container. A plastic container that has oxygen barrier properties and prevents elution of additives in plastic by arranging them.

However, the above-mentioned plastic container (1) does not consider the prevention of the leaching of the fat to the outer wall of the container. On the other hand, although the plastic container of (2) can solve the problems of (a) and (b) above, delamination by heat sterilization is caused because the heat resistance of the inner layer and the intermediate layer is insufficient. It cannot be said that all the basic properties required for a medical bag such as transparency, heat resistance, strength and flexibility are satisfied, because it has a problem that it may occur.

An object of the present invention is to prevent the lipophilic substance (for example, fat content in a fat emulsion) from seeping out of the container when a drug containing a lipophilic substance such as a fat emulsion is contained. It is an object of the present invention to provide a multilayer film and container suitable for medical use, which can be obtained and has excellent transparency, heat resistance, strength and flexibility.

[0009]

A multilayer film of the present invention for solving the above-mentioned problems is a film having a four-layer structure composed of an ethylene / α-olefin copolymer, and the resin constituting each layer has a density of , 1st layer: 0.935 to 0.950 g / cm ³ 2nd layer: 0.885 to 0.920 g / cm ³ 3rd layer: 0.930 to 0.950 g / cm ³ 4th layer: 0. It is 925 to 0.940 g / cm ³ , and the resin density of the third layer is higher than the resin density of the fourth layer.

The container of the present invention is characterized in that the multilayer film of the present invention is used, and the first layer of the multilayer film is formed as the outer layer of the container and the fourth layer is formed as the inner layer of the container. The multilayer film of the present invention having the above layer structure is excellent in transparency, heat resistance, strength and flexibility.
In addition, since the density of the resin forming the third layer is higher than the density of the resin forming the first and second layers and the fourth layer in this multilayer film, the fat emulsion is placed in a container formed by using the multilayer film. It is possible to prevent the fat content in the fat emulsion from seeping out of the container even after long-term storage.

In the above-mentioned multilayer film of the present invention, the density of the resin constituting each layer is in the order of the first layer: 0.935 to 0.945 g / cm ³ the second layer: 0.900 to 0.910 g / cm ³ 3 layers: 0.935~0.945g / cm ³ layer 4: may be 0.925~0.935g / cm ^3.

Further, (i) the resin of the second layer has a density of 0.90.
0 to 0.920 g / cm ³ of ethylene / α-olefin copolymer 30 to 60 wt% and a density of 0.900 g / cm
Ethylene / α-olefin elastomer 40 less than ³
Or (ii) the resin of the second layer is the mixed resin of (i) above, and has a density of 0.95.
It is a mixed resin in which high-density polyethylene of 5 g / cm ³ or more is mixed at a ratio of 10 wt% or less, or (ii
i) The resin used for the first layer and / or the third layer and / or the fourth layer is a resin in which an ethylene / α-olefin copolymer having a density of 0.945 g / cm ³ or more is mixed at a ratio of 10% by weight or less. The film and the container using the same are more excellent in heat resistance, flexibility and the like.

Further, in the multilayer film of the present invention,
The heat resistance and strength are such that the ratio of the thickness of each layer is in the range of 1st layer: 5 to 15%, 2nd layer: 50 to 70%, 3rd layer: 5 to 40%, 4th layer: 5 to 15%. It is preferable for obtaining a container having excellent flexibility and the like.

[0014]

BEST MODE FOR CARRYING OUT THE INVENTION The resins constituting the film of the present invention are all ethylene / α-olefin copolymers. Examples of the α-olefin include propylene, 1-
Butene, 1-pentene, 1-hexene, 4-methyl-1
Examples thereof include pentene, 1-heptene, 1-octene, 1-nonene, 1-decene, 1-undecene, 1-dodecene and the like having 3 to 12 carbon atoms.

The resin of each layer constituting the multilayer film of the present invention will be described in more detail below. In the present invention, physical properties such as density and melt flow rate are AS
It is measured based on TM regulations. * Regarding the first layer For the purpose of imparting mechanical strength (particularly tensile strength) and heat resistance, the density is in the range of 0.935 to 0.950 g / cm ³ ,
It is preferable to use 0.935 to 0.945 g / cm ³ , specifically about 0.940 g / cm ³ of resin. Among them, the melt flow rate (MFR) is 1.5-2.5g
/ 10 minutes (190 ° C.) and a melting point of 120 to 130 ° C. are more preferable.

In order to further increase heat resistance, the first layer may be mixed with an ethylene / α-olefin copolymer having a density of 0.945 g / cm ³ or more at a ratio of 10% by weight or less. Also in that case, the density of the entire resin is set within the above range. The thickness of the first layer is appropriately 5 to 15% of the whole multilayer film. * Regarding the second layer In order to give the container high flexibility, the ethylene / α-olefin copolymer used in this layer has a density of 0.885-
0.920 g / cm ³ , preferably density 0.900-
It is preferably 0.910 g / cm ³ . It is also preferable to use a linear copolymer in order to maintain transparency,
The MFR is preferably 0.5 to 4.0 g / 10 minutes (190 ° C), and the melting point is preferably 105 to 120 ° C.

Furthermore, this layer contains a mixture of two or more resins.
Can be used, and in particular, a density of 0.900 to 0.920
g / cm^Three30-60% by weight of resin, density 0.900
g / cm^ThreeLess than ethylene / α-olefin based elastomer
A resin mixture of 40-70% by weight of mer is preferred.
is there. Above all, the mixed resin has a density of 0.955 g / cm. ^Three
Mix the above high-density polyethylene at a ratio of 10% by weight or less.
The combined resin has both flexibility and heat resistance.
Preferred. Examples of the high-density polyethylene include α-ole
It may be either a fin copolymer or a homopolymer.
Even if mixed resin is used,
The degree is set within the above range.

The thickness of the second layer is 50 for the entire multilayer film.
Appropriately 70%. * About the 3rd layer The role of the 3rd layer is to prevent the oil-soluble substance (fat content in the fat emulsion) contained in the contents of the container from seeping out to the outer wall of the container, and to maintain the strength (waist) of the entire film. That is.

Therefore, in order to achieve this object, the third
For the layer, an ethylene / α-olefin copolymer having a density of 0.930 to 0.950 g / cm ³ , preferably 0.935 to 0.945 g / cm ³ is used. The density range of the resin that can be used for the third layer partially overlaps with the density range of the fourth layer described below, but the density of the resin of the third layer is lower than that of the resin of the fourth layer. A larger size is required to achieve the above purpose.

The resin may be a linear or branched resin, but is preferably a linear polymer in order to maintain the affinity with other layers. The MFR of the resin for the third layer is preferably 1.5 to 2.5 g / 10 minutes (190 ° C.) and the melting point is preferably 120 to 130 ° C. The third layer is made of ethylene / α- with a density of 0.945 g / cm ³ or more in order to increase the strength (waist) of the entire film.
The olefin copolymer may be mixed in a proportion of 10% by weight or less. Also in this case, the density of the entire resin of the third layer is set within the above range.

The thickness of the third layer is 5 to the total thickness of the multilayer film.
40% is suitable. * About the 4th layer Although the 4th layer can be easily heat-welded to form a container, it does not cause so-called blocking such that the inner surfaces of the container are welded to each other due to sterilization under high temperature conditions. With a density of 0.925 to 0.940 g / cm
³ , preferably with a density of 0.925 to 0.935 g / cm ^3.
Of resin is used. The melting point of the resin is 120 to 130.
The temperature is preferably in the range of ° C.

The fourth layer may be mixed with an ethylene / α-olefin copolymer having a density of 0.945 g / cm ³ or more at a ratio of 10% by weight or less in order to further improve heat resistance and blocking resistance. it can. Also in that case, the density of the entire resin is set within the above range. The thickness of the fourth layer is appropriately 5 to 15% of the whole multilayer film.

Examples of the method for producing the film of the present invention include a water-cooled or air-cooled coextrusion inflation method, a coextrusion T-die method, a dry lamination method, an extrusion lamination method, and the like. From the standpoint of hygiene and the like, the water-cooled coextrusion inflation method and the coextrusion T-die method are preferable. In either method, it is necessary to carry out at a temperature at which the resin in each layer melts, but if the temperature is raised too high, a part of the resin is thermally decomposed, and the decomposition products may deteriorate the performance. Therefore, the temperature condition for producing the film of the present invention is usually 150 to 250 ° C., preferably 170 to 200.
C is desirable. Further, the resin forming each layer is
The difference in MFR should be minimized to maintain transparency.

The thickness of the film of the present invention produced by the above method is generally 100 to 300 μm, but it can be appropriately increased or decreased according to the purpose of use and the like, and a sufficient strength is maintained even at a thickness of about 200 μm. The container of the present invention is formed by cutting the tube-shaped or sheet-shaped film obtained above by a usual method, heat-sealing it, and further attaching a mouth member or the like by means such as heat-sealing to form it into a predetermined shape and size. Manufactured by.

The conditions for heat sealing the film are as follows:
The temperature can be raised up to about 120 ℃ -160 ℃,
For example, in the case of a film having a thickness of about 200 μm, it can be sealed in about 0.5 to 3 seconds in the above temperature range. As a specific example of the container of the present invention, for example, as shown in FIG. 1, a container having a mouth member 2 having a rubber stopper 3 attached to the upper part of the container 1 can be cited.

The shape of the mouth member is not particularly limited, and any shape can be adopted depending on the purpose of use of the drug. For example, as another example of the container of the present invention, as shown in FIG. 2, a container having a rubber plug 31 and a mouth member 21 having a hollow double-ended needle 4 is attached to the upper part of the container 11. According to the mouth member shown in FIG. 2, when the seal 5 is opened and a drug container such as a vial bottle is inserted into the outer jacket 6,
The double-ended needle 4 held by the double-ended needle holder 7 penetrates the rubber stopper 31 and the container 11 is opened. Therefore, the operation of taking out the contents of the container 11 can be easily performed.

As the mouth members 2 and 21, ethylene / α is used.
It is preferable to use a molded product of an olefin copolymer because it can be well welded to the fourth layer of the film of the present invention.

[0028]

EXAMPLES Examples of evaluation experiments on containers molded using the multilayer film according to the present invention will be described below.
First, a synthetic resin and a laminated sheet having a layer constitution shown in Table 1 were molded by a water-cooled coextrusion and inflation method to obtain a multilayer film. Next, using this multilayer film, a medical container 1 having an internal volume of 500 ml as shown in FIG. 1 was molded. The heat sealing of the film at the time of molding the container was performed at 140 ° C. for 2 seconds.

Further, regarding the obtained medical container 1,
Various characteristics were evaluated by the following methods. That is, regarding the heat resistance, the container was filled with distilled water and subjected to high-pressure steam sterilization treatment at 110 ° C. for 40 minutes to visually observe the state of deformation, bag breakage, and seal leakage. The drop test was performed by filling the container with distilled water and refrigerating at about 4 ° C.
The state of bag breakage and seal leakage when dropped from a height of 1.2 m was visually observed.

For flexibility, the spontaneous discharge of the content liquid was visually observed. Regarding the transparency, the container was filled with distilled water and subjected to high-pressure steam sterilization treatment in the same manner as described above, and the transparency of the film was visually observed. In the leaching test, a container was filled with a certain amount of soybean oil and stored at 60 ° C. for 5 days, and then the outer surface of the container was coated with a certain amount of acetonitrile-tetrahydrofuran (7: 3).
The soybean oil contained in the washing liquid was analyzed by high performance liquid chromatography.

On the other hand, as a comparative example, a synthetic resin and a laminated sheet having a layer constitution shown in Table 1 were molded in the same manner as above to obtain a multilayer film, and then a container was formed in the same manner as above, and various characteristics thereof were evaluated. . The abbreviations in Table 1 are as follows. -PE-1 = linear medium density polyethylene (ethylene-1
-Butene copolymer) [manufactured by Mitsui Petrochemical Co., Ltd .; density = 0.940 g / cm ³ , MFR = 2.1 g / 10 minutes (190 ° C.)] PE-2 = linear low-density polyethylene ( Ethylene / 1
-Butene copolymer) [manufactured by Mitsui Petrochemical Co., Ltd .; density = 0.920 g / cm ³ , MFR = 2.1 g / 10 min (190 ° C.)] PE-3 = linear medium density polyethylene ( Ethylene / 1
-Butene copolymer) [manufactured by Mitsui Petrochemical Co., Ltd .; density = 0.930 g / cm ³ , MFR = 2.1 g / 10 min (190 ° C.)]-EE-1 = ethylene / 1-butene copolymer Combined elastomer [Mitsui Petrochemical Industry Co., Ltd .; density = 0.885 g /
cm ³ , MFR = 0.5 g / 10 min (190 ° C.)] HP-1 = high density polyethylene (homopolymer) [manufactured by Mitsui Petrochemical Industry Co., Ltd .; density = 0.965 g / c]
m ³ , MFR = 15 g / 10 min (190 ° C.)] In each evaluation of heat resistance, drop test, flexibility and transparency, ⊚ is very good, ◯ is good, and Δ is a little bad.
X indicates a defect. In the exudation test, ⊚ indicates that no soybean oil exudation was observed, and x indicates that soybean oil exudation was clearly observed.

[0032]

[Table 1]

As is clear from Table 1 above, the film and container of the present invention are excellent in flexibility, heat resistance, strength and transparency, and the bleeding of the fat emulsion to the outside is suppressed. Although the container for the fat emulsion has been described, the present invention is not limited to the use for the fat emulsion and can be applied to the use for the liquid drug containing other lipophilic substance.

[0034]

INDUSTRIAL APPLICABILITY According to the present invention, a lipophilic substance in a drug (for example, a fat emulsion) (Fat content) does not exude to the outside, and has * heat resistance that can withstand high-temperature sterilization such as high-pressure steam sterilization and hot water sterilization, and heat sealing at high temperatures. * Excellent strength and normal use In the above, there is an effect that it is possible to provide a container capable of maintaining excellent flexibility and transparency even after sterilization without causing bag breakage or seal leakage.

Therefore, the multilayer film and container of the present invention can be suitably used as a medical container such as an infusion bag for administering a fat emulsion.

[Brief description of the drawings]

FIG. 1 is a front view showing an example of a container of the present invention.

FIG. 2 is a partial cross-sectional view showing another example of the container of the present invention.

[Explanation of symbols]

 1 container 11 containers

Claims (7)

[Claims] 1. A film having a four-layer structure comprising an ethylene / α-olefin copolymer, wherein the density of the resin constituting each layer is in order of the first layer: 0.935 to 0.950 g / cm ³ second Layer: 0.885 to 0.920 g / cm ³ Third layer: 0.930 to 0.950 g / cm ³ Fourth layer: 0.925 to 0.940 g / cm ³ and resin density of the third layer Is larger than the resin density of the fourth layer, a multilayer film. 2. The density of the resin forming each layer is in the order of: first layer: 0.935 to 0.945 g / cm ³ second layer: 0.900 to 0.910 g / cm ³ third layer: 0.935. -0.945g / cm < ³ > 4th layer: 0.925-0.935g / cm < ³ >, The resin density of a 3rd layer is larger than the resin density of a 4th layer, The multilayer film of Claim 1. 3. The resin of the second layer has a density of 0.900 to 0.9.
20 g / cm ³ ethylene / α-olefin copolymer 3
The multilayer film according to claim 1 or 2, which is a mixed resin of 0 to 60% by weight and 40 to 70% by weight of an ethylene / α-olefin elastomer having a density of less than 0.900 g / cm ³ . 4. The resin of the second layer has a density of 0.955 g / cm.
The multilayer film according to claim ^{3, wherein 3} or more high-density polyethylene is mixed in a proportion of 10% by weight or less. 5. The resin used for the first layer and / or the third layer and / or the fourth layer contains an ethylene / α-olefin copolymer having a density of 0.945 g / cm ³ or more at a ratio of 10% by weight or less. The multilayer film according to any one of claims 1 to 4, which is mixed. 6. The thickness ratio of each layer is in the range of the first layer: 5 to 15%, the second layer: 50 to 70%, the third layer: 5 to 40%, and the fourth layer: 5 to 15%. The multilayer film according to any one of 1 to 5. 7. A container characterized by using the multilayer film according to any one of claims 1 to 6, wherein the first layer of the multilayer film is formed as an outer layer of the container and the fourth layer is formed as an inner layer of the container. .