JP2000141548A - Multilayered plastic tube container excellent in chemical resistance - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a multilayered plastic tube container excellent in the preservability of content and chemical resistance, especially, a multilayered plastic tube container for a drug or a quasi-drug excellent in the combination of the preservability of content and adhesiveness even in a case filled with a W/O type or O/W type emulsion. SOLUTION: A multilayered plastic tube container for a drug or a quasi-drug comprises a laminate consisting of an outer layer 1 of a linear olefinic resin, an adhesive layer 2, an intermediate layer 3 comprising a cyclic olefinic copolymer, an adhesive layer 4 and an inner layer 5 comprising an acrylonitrile resin with high nitrile content. The outer layer 1 has a thickness of 5-600 μm and the intermediate layer 3 has a thickness of 5-100 μm and the inner layer 5 has a thickness of 5-100 μm and the adhesive layer 2 has a thickness of 5-100 μm.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a multilayer plastic tube container having excellent preservability of contents and chemical resistance, and more particularly, to a pharmaceutical container excellent in preservability of contents and interlayer adhesion. Or, it relates to a multilayer plastic tube container for quasi-drugs.

[0002]

2. Description of the Related Art Conventionally, for use as an external anti-inflammatory / analgesic, W / O type (water-in-oil type) or O / W type (water-in-oil type) containing an aromatic oxycarboxylic acid ester such as methyl salicylate in an oil phase. (Oil-in-water) emulsions are widely used, and such emulsions are widely used both as pharmaceuticals and quasi-drugs.

[0003] This emulsion is generally filled in a tube container and used for each application. However, when the above-mentioned emulsion is filled in a multilayer plastic tube container, the preservability of the contents is still insufficient. Further, there arises a problem that the adhesive strength between the respective layers of the container is remarkably reduced with time.

Various types of multi-layer plastic tube containers have been proposed, for example, see Japanese Patent Application Laid-Open No. H06-211.
No. 257 discloses an ethylene vinyl alcohol copolymer in which a body, a shoulder, and a mouth and neck are provided with a surface resin layer made of an olefin resin, an inner peripheral resin layer made of a polyacrylonitrile resin, and both. An extruded tube container formed of a blow-molded article having a laminated structure having an intermediate layer made of a barrier resin layer as described above is described.

Further, it is known that a cyclic olefin copolymer has excellent resistance to water vapor permeation, and it is necessary to form a multilayer plastic container in combination with an oxygen barrier resin such as an ethylene vinyl alcohol copolymer. Is also already known.

[0006]

The above-mentioned conventional multi-layer plastic tube container exhibits generally satisfactory storage stability for many contents, but contains an aromatic oxycarboxylic acid ester in the oil phase. No satisfactory storage stability has yet been obtained for W / O or O / W emulsions containing

That is, in the above-described container having polyacrylonitrile as the inner surface layer, since the moisture in the emulsion permeates the vessel wall and the composition of the emulsion changes from that at the time of filling, the viscoelasticity of the drug falls within an appropriate range. Inconveniences such as detachment or loss of smoothness during application occur.

Further, in a multilayer container provided with a cyclic olefin copolymer as an intermediate layer, the surface of the intermediate layer is susceptible to attack by an aromatic oxycarboxylic acid ester, and the interlayer adhesive strength is significantly reduced with time. is there.

Accordingly, an object of the present invention is to provide a multilayer plastic tube container excellent in preservability and chemical resistance of the contents, particularly a W / O type or O / O type containing an aromatic oxycarboxylic acid ester in an oil phase. It is an object of the present invention to provide a multi-layer plastic tube container for pharmaceuticals or quasi-drugs, which is excellent in combination of the preservability and adhesiveness of the contents even when filled with a W-type emulsion.

[0010]

According to the present invention, a linear olefin resin outer layer / adhesive layer / intermediate layer composed of a cyclic olefin copolymer / adhesive layer / acrylonitrile based on high nitrile content A multilayer plastic tube container for pharmaceuticals or quasi-drugs, comprising a laminate of resin inner layers, is provided. The present invention is particularly effective when the pharmaceutical or quasi-drug is a W / O or O / W emulsion containing an aromatic oxycarboxylic acid ester in an oil phase. In the tube container of the present invention, the outer layer has a thickness of 5 to 600 μm, and the intermediate layer has a thickness of 5 to 1 μm.
Preferably, the thickness is 00 μm, the inner layer has a thickness of 5 to 100 μm, and the adhesive layer has a thickness of 5 to 100 μm. Further, the inner layer is made of a resin composition containing titanium dioxide having a particle size of 0.01 to 10 μm, and the resin composition contains 0.1% titanium dioxide per 100 parts by weight of resin.
It is preferable to contain 5 to 20 parts by weight.

[0011]

DESCRIPTION OF THE PREFERRED EMBODIMENTS [Operation] In FIG. 1 showing the cross-sectional structure of a tube container of the present invention, the container wall has a linear olefin resin outer layer 1, an adhesive layer 2,
Intermediate layer 3 made of cyclic olefin copolymer, adhesive layer 4, inner layer 5 of acrylonitrile resin having high nitrile content
It consists of a laminate.

In the tube container of the present invention, a linear olefin resin is used as the outer layer 1 because of the compressive deformation required for extruding the contents and the airbag (return deformation of the container wall) after extruding the contents. This is because sufficient plasticity can be obtained to prevent the air from being sucked into the tube by the air.

The reason for using a cyclic olefin copolymer as the intermediate layer 3 is to prevent the permeation of water vapor from the contents through the vessel wall. In particular, in the emulsion-based drug described above, the change in the physical properties of the drug due to a change in water is remarkable, but in the present invention, the cyclic olefin-based copolymer is used as the intermediate layer to suppress the water vapor permeation to a low level. Even when the package of the container has been aged for a long period of time, the extrudability of the contents, the shape retention of the extrudate, the applicability to the affected area and the like, and the smoothness to the skin are maintained in the same state as at the time of filling. It becomes possible.

The tube container of the present invention is characterized in that an acrylic nitrile resin having a high nitrile content is used as the inner layer 5 in combination with the intermediate layer of the cyclic olefin copolymer. It has already been pointed out that aromatic oxycarboxylates such as methyl salicylate attack the surface of the cyclic olefin-based copolymer intermediate layer over time and significantly reduce its adhesiveness, but among various barrier resins, On the other hand, only the acrylonitrile resin acts so as to prevent the aromatic oxycarboxylic acid ester from attacking the intermediate layer of the cyclic olefin copolymer.

Most of what is generally called an oxygen barrier resin has a strong hydrogen bond, and in this respect, both the acrylonitrile resin and the ethylene vinyl alcohol copolymer used in the present invention are at the same level. In addition, the ethylene vinyl alcohol copolymer is hydrophilic, and from this viewpoint, it is expected that the ethylene vinyl alcohol copolymer has a higher barrier property against the aromatic oxycarboxylic acid ester.

However, as shown in an example described later,
In the case of a multilayer tube container having an ethylene-vinyl alcohol copolymer as the inner layer, the interlayer adhesion to the cyclic olefin-based copolymer intermediate layer is significantly reduced with time, whereas the acrylonitrile-based resin is used as the inner layer. In
Such delamination and reduction in adhesive strength are effectively suppressed. This is an unexpected effect according to the present invention.

In the multilayer plastic tube container of the present invention, the thickness of each resin layer also has an appropriate range in terms of the balance of certain physical properties. 5-6 olefin resin outer layer
A thickness of 00 μm and a cyclic olefin copolymer intermediate layer of 5
The thickness of the acrylonitrile resin inner layer is preferably 5 to 100 μm, and the thickness of the adhesive layer on both sides of the intermediate layer is preferably 5 to 100 μm.

When the thickness of the outer layer of the olefin resin is less than the above range, the effect of protecting the vessel wall by the outer layer becomes insufficient. On the other hand, when the thickness of the outer layer exceeds the above range, the extrusion characteristics and air suck required for the tube container are reduced. The anti-back property tends to be insufficient. If the thickness of the intermediate layer of the cyclic olefin copolymer is less than the above range, the water vapor transmission resistance becomes insufficient. On the other hand, if the thickness of the intermediate layer exceeds the above range, the extrusion characteristics and air suck-back required for the tube container are also required. Prevention tends to be insufficient. Further, when the thickness of the acrylonitrile-based resin inner layer is less than the above range, the influence of permeation through the inner layer such as an aromatic oxycarboxylate appears, the interlayer adhesion resistance is reduced, and the thickness of the inner layer exceeds the above range. In addition, the extrusion characteristics and air suckback prevention required for the tube container tend to be insufficient. The thickness of the adhesive layer also has a certain range. If the thickness of the adhesive layer is less than the above range, the interlayer adhesion resistance tends to decrease.If the thickness of the adhesive layer exceeds the above range, it is necessary for a tube container. There is a tendency that excellent extrusion characteristics and air suckback prevention are insufficient.

[Tube Container] In FIG. 2, which shows an example of the multilayer plastic tube container of the present invention, this multilayer tube container comprises a tube container body 11 and a lid 12, and the tube container body 11 is shown in FIG. It has a threaded extrusion port 13 integrally formed by hollow molding of a multi-layer parison having the illustrated layer configuration, a conical shoulder portion 14 connected thereto, and a thin cylindrical body portion 15. This cylindrical body 15
Has a cut edge 16, after filling the contents from this edge, the opposite inner surfaces of the body are fused together,
A sealed bottom is formed.

[Acrylonitrile-based resin] The acrylonitrile-based resin used for the inner layer of the tube container of the present invention must be capable of being melt-molded and have resistance to permeation of an aromatic oxycarboxylic acid ester.

This resin generally has a content of acrylonitrile units in the resin of 50 to 95 mol%, preferably 55 to 70 mol%. When the content of the acrylonitrile unit is less than the above range, the penetration of the aromatic oxycarboxylic acid ester and the like into the vessel wall is not sufficiently prevented, and the interlayer adhesion is inferior to those in the above range. On the other hand, when the content of the acrylonitrile unit exceeds the above range, melt molding tends to be difficult.

As the acrylonitrile resin, a copolymer derived from acrylonitrile and another ethylenically unsaturated monomer or diolefin monomer, a blend thereof, or a graft modified product thereof is used. . Suitable copolymers include acrylonitrile-butadiene copolymer, acrylonitrile-styrene copolymer, acrylonitrile-styrene-butadiene copolymer, and blends thereof are also used.

Further, a hynitrile resin obtained by grafting the above copolymer or a blend thereof with an ethylenically unsaturated monomer mainly composed of acrylonitrile can be advantageously used for the purpose of the present invention.

The acrylonitrile resin used should have a molecular weight sufficient to form a film.
It is desirable that the melt flow rate (MFR) at 200 ° C. under a load of 5 kg is in the range of 2 to 10 g / 10 min.

The acrylonitrile-based resin forming the inner layer of the tube container in the present invention includes titanium dioxide (TiO ₂ ).
It is preferable to include a white pigment such as That is, the acrylonitrile-based resin inner layer tends to whiten when contacted with warm water. This is considered to be because the acrylonitrile-based resin adsorbs moisture under the above conditions, and as a result, a void having a diameter of about 0.5 μm is formed. On the other hand, when the acrylonitrile-based resin constituting the inner layer is filled with a white pigment such as titanium dioxide, the voids are hidden, which is convenient.

As a white pigment, titanium dioxide is excellent in terms of hiding properties and in terms of resistance to contents. As the titanium dioxide, either a rutile type or an anatase type can be used, and the particle size is 0.1 to 1 μm.
Are suitable. Titanium dioxide is 0.5% based on 100 parts by weight of the acrylonitrile resin.
It is preferred to mix in an amount of from 20 to 20 parts by weight.

[Cyclic Olefin Copolymer] As the cyclic olefin copolymer, a copolymer of a cyclic olefin and another olefin is used, and this copolymer is an amorphous to low crystalline copolymer. It is preferred that As the olefin from which the cyclic olefin-based copolymer (COC) is derived, ethylene is suitable.
Butene, 1-pentene, 1-hexene, 1-octene,
An α-olefin having 3 to 20 carbon atoms such as 3-methyl 1-pentene and 1-decene is used alone or in combination with ethylene.

As the cyclic olefin, basically, an alicyclic hydrocarbon compound having an ethylenically unsaturated bond and a bicyclo ring, particularly bicyclo [2,2,1] hept-2-
It is a hydrocarbon compound having an ene skeleton, and specific examples thereof include, but are not limited to, the following.

Bicyclo [2.2.1] hept-2-ene derivative; for example, the following formula (1)

Embedded image In the formula, R is a hydrogen atom, an alkyl group, a cycloalkyl group,
Alternatively, it is an alkylidene group, and n is a number of 1 to 4 (the same applies hereinafter), and bicyclo [2.2.
1] Hept-2-ene derivative. In particular, bicyclo [2.2.1] hept-2-ene 6-methylbicyclo [2.2.1] hept-2-ene 5,6-dimethylbicyclo [2.2.1] hept-2-
Ene 1-methylbicyclo [2.2.1] hept-2-ene 6-ethylbicyclo [2.2.1] hept-2-ene 6-n-butylbicyclo [2.2.1] hept-2- Ene 6-isobutylbicyclo [2.2.1] hept-2-ene 7-methylbicyclo [2.2.1] hept-2-ene.

[0030] tricyclo ^[4.3.0.1 2.5] -3
-Decene derivative; for example, the following formula (2)

Embedded image In represented by tricyclo ^[4.3.0.1 2.5] -3-
Decene derivatives. In particular, tricyclo ^[4.3.0.1 2.5] -3- decene 2-methyl-tricyclo ^[4.3.0.1 2.5] -3-
Decene 5-methyl-tricyclo ^[4.3.0.1 2.5] -3-
Desen.

[0031] tricyclo ^[4.4.0.1 2.5] -3
-Undecene derivatives; for example, the following formula (3)

Embedded image In represented by tricyclo ^[4.4.0.1 2.5] -3-
Undecene derivatives. In particular, tricyclo ^[4.3.0.1 2.5] -3- undecene 10-methyl-tricyclo ^[4.4.0.1 2.5] -3
-Undecene.

Tetracyclo [4.4.0.1 ^2.5 . 1
^7.10 ] -3-dodecene derivatives, for example, the following formula (4)

Embedded imageTetracyclo [4.4.0.1 represented by^2.5. 1
^7.10] -3-dodecene derivatives. In particular, tetracyclo [4.4.0.1^2.5. 1^7.10]-
3-dodecene 8-methyltetracyclo [4.4.0.1^2.5. 1
^7.10] -3-dodecene 8-ethyltetracyclo [4.4.0.1^2.5. 1
^7.10] -3-dodecene 8-propyltetracyclo [4.4.0.1^2.5. 1
^7.10] -3-dodecene 8-butyltetracyclo [4.4.0.1^2.5. 1
^7.10] -3-dodecene 8-isobutyltetracyclo [4.4.0.1^2.5.
1^7.10] -3-dodecene 8-hexyltetracyclo [4.4.0.1^2.5. 1
^7.10] -3-dodecene 8-cyclohexyltetracyclo [4.4.0.1
^2.5. 1^7.10] -3-dodecene 8-stearyltetracyclo [4.4.0.1^2.5.
1^7.10] -3-dodecene 5,10-dimethyltetracyclo [4.4.0.1
^2.5. 1^7.10] -3-dodecene 2,10-dimethyltetracyclo [4.4.0.1
^2.5. 1^7.10] -3-dodecene 8,9-dimethyltetracyclo [4.4.0.
1^2.5. 1^7.10] -3-dodecene 8-ethyl-9-methyltetracyclo [4.4.0.1
^2.5. 1^7.10] -3-dodecene 11,12-dimethyltetracyclo [4.4.0.1
^2.5. 1^7.10] -3-dodecene 2,7,9-trimethyltetracyclo [4.4.0.1
^2.5. 1^7.10] -3-dodecene 2,7-dimethyl-9-ethyltetracyclo [4.4.
0.1^2.5. 1^{7 . 10}] -3-dodecene 9-isobutyl-2,7-dimethyltetracyclo [4.
4.0.1.^2.5. 1^7.10] -3-dodecene 9,11,12-trimethyltetracyclo [4.4.
0.1^2.5. 1^{7. 10}] -3-dodecene 9-ethyl-11,12-dimethyltetracyclo [4.
4.0.1.^2.5. 1^7.10] -3-dodecene 9-isobutyl-11,12-dimethyltetracyclo
[4.4.0.1^{2. 5}. 1^7.10] -3-dodecene 5,8,9,10-tetramethyltetracyclo [4.
4.0.1.^2.5. 1 ^7.10] -3-dodecene 8-ethylidenetetracyclo [4.4.0.1^2.5.
1^7.10] -3-Dodecene 8-ethylidene-9-methyltetracyclo [4.4.
0.1^2.5. 1^{7. 10}] -3-Dodecene 8-ethylidene-9-ethyltetracyclo [4.4.
0.1^2.5. 1^{7. 10}] -3-Dodecene 8-ethylidene-9-isopropyltetracyclo [4.
4.0.1.^2.5. 1^7.10] -3-Dodecene 8-ethylidene-9-butyltetracyclo [4.4.
0.1^2.5. 1^{7. 10}] -3-dodecene 8-n-propylidenetetracyclo [4.4.0.1
^2.5. 1^7.10] -3-Dodecene 8-n-propylidene-9-methyltetracyclo [4.
4.0.1.^2.5. 1^7.10] -3-Dodecene 8-n-propylidene-9-ethyltetracyclo [4.
4.0.1.^2.5. 1^7.10] -3-dodecene 8-n-propylidene-9-isopropyltetracyclo
[4.4.0.1^{2 . 5}. 1^7.10] -3-Dodecene 8-n-propylidene-9-butyltetracyclo [4.
4.0.1.^2.5. 1^7.10] -3-dodecene 8-isopropylidenetetracyclo [4.4.0.1
^2.5. 1^7.10] -3-Dodecene 8-isopropylidene-9-methyltetracyclo [4.
4.0.1.^2.5. 1^7.10] -3-Dodecene 8-isopropylidene-9-ethyltetracyclo [4.
4.0.1.^2.5. 1^7.10] -3-Dodecene 8-isopropylidene-9-isopropyltetracyclo
[4.4.0.1^{2 . 5}. 1^7.10] -3-Dodecene 8-isopropylidene-9-butyltetracyclo [4.
4.0.1.^2.5. 1^7.10] -3-dodecene.

Pentacyclo [6.5.1.1 ^3.6 . 0
^2.7 . ^09.13 ] -4-pentadecene derivative; for example, the following formula (5)

Embedded imagePentacyclo [6.5.1.1] represented by^3.6. 0
^2.7. 0^9.13] -4-Pentadecene derivatives. Special
Pentacyclo [6.5.1.1]^3.6. 0^2.7. 0
^9.13] -4-Pentadecene 1,3-dimethylpentacyclo [6.5.1.
1^3.6. 0^2.7. 0^{9. 13}] -4-Pentadecene 1,6-dimethylpentacyclo [6.5.1.
1^3.6. 0^2.7. 0^{9. 13}] -4-pentadecene 14,15-dimethylpentacyclo [6.5.1.1]
^3.6. 0^2.7. 0 ^9.13] -4-pentadecene.

Pentacyclo [7.4.0.1 ^2.5 . 1
^9.12 . 0 ^8.13 ] -3-pentadecene derivative, for example, the following formula (6)

Embedded image Pentacyclo [7.4.0.1 ^2.5 . 1
^9.12 . 0 ^8.13 ] -3-pentadecene derivatives. In particular, pentacyclo [7.4.0.1 ^2.5 . ^19.12 . 0
^8.13 ] -3-pentadecene methyl-substituted pentacyclo [7.4.0.1 ^2.5 . 1
^9.12 . 0 ^8.13 ] -3-pentadecene.

Pentacyclo [6.5.1.1 ^3.6 . 0
^2.7 . 0 ^9.13] 4,10 penta decadiene derivative, for example, the following formula (7)

Embedded image Pentacyclo [6.5.1.1 ^3.6 . 0
^2.7 . 0 ^9.13] 4,10 penta octadecadienoic derivatives. In particular, pentacyclo [6.5.1.1 ^3.6 . 0 ^2.7 . 0
^9.13 ] -4,10-pentadecadiene.

Pentacyclo [8.4.0.1 ^2.5 . 1
^9.12 . 0 ^8.13 ] -3-hexadecene derivative, for example, the following formula (8)

Embedded image Pentacyclo [8.4.0.1 ^2.5 . 1
^9.12 . 0 ^8.13 ] -3-Hexadecene derivative. In particular, pentacyclo [8.4.0.1 ^{2.5. 19.12} . 0
^8.13 ] -3-Hexadecene 11-methyl-pentacyclo [8.4.0.1 ^2.5 .
^19.12 . 0 ^{8. 13} ] -3-Hexadecene 11-ethyl-pentacyclo [8.4.0.1 ^2.5 .
^19.12 . 0 ^{8. 13} ] -3-Hexadecene 10,11-dimethyl-pentacyclo [8.4.0.1
^2.5 . ^19.12 . 0 ^8.13 ] -3-Hexadecene.

Pentacyclo [6.6.1.1 ^3.6 . 0
^2.7 . ^09.14 ] -4-Hexadecene derivative, for example, the following formula (9)

Embedded imagePentacyclo [6.6.1.1 represented by^3.6. 0
^2.7. 0^9.14] -4-Hexadecene derivative. Special
Pentacyclo [6.6.1.1^3.6. 0^2.7. 0
^9.14] -4-Hexadecene 1,3-dimethylpentacyclo [6.6.1.
1^3.6. 0^2.7. 0^{9. 14}] -4-Hexadecene 1,6-dimethylpentacyclo [6.6.1.
1^3.6. 0^2.7. 0^{9. 14}] -4-Hexadecene 15,16-dimethylpentacyclo [6.6.1.1
^3.6. 0^2.7. 0 ^9.14] -4-Hexadecene.

Hexacyclo [6.6.1.1 ^3.6 . 1
^10.13 . 0 ^2.7 . 0 ^9.14] -4-heptadecene derivatives, for example, the following formula (10)

Embedded imageHexacyclo [6.6.1.1 represented by^3.6. 1
^10.13. 0^2.7. 0 ^9.14] -4-heptadece
Derivatives. In particular, hexacyclo [6.6.1.1^3.6. 1^10.13.
0^2.7. 0^{9.1 4}] -4-Heptadecene 12-methylhexacyclo [6.6.1.1^3.6. 1
^10.13. 0^{2. 7}. 0^9.14] -4-heptadece
12-ethylhexacyclo [6.6.1.1^3.6. 1
^10.13. 0^{2. 7}. 0^9.14] -4-heptadece
12-isobutylhexacyclo [6.6.1.
1^3.6. 1^10.13. 0 ^2.7. 0^9.14] -4
-Heptadecene 1,6,10-trimethyl-12-isobutylhexyl
Black [6.6.1.1^3.6. 1^10.13.
0^2.7. 0^9.14] -4-Heptadecene.

Heptacyclo [8.7.0.1 ^2.9 . 1
^4.7 . 1 ^11.17 . 0 ^3.8 . 0 ^12.16 ] -5
-Eicosene derivatives, for example, the following formula (11)

Embedded imageHeptacyclo [8.7.0.1 represented by^2.9. 1
^4.7. 1^11.17. 0 ^3.8. 0^12.16] -5
-Eicosene derivatives. In particular, heptacyclo [8.7.0.1^2.9. 1^4.7. 1
^11.17. 0^3.8. 0^12.16] -5-eicose
N.

Heptacyclo [8.7.0.1 ^3.6 . 1
^10.17 . 1 ^12.15 . 0 ^{2. 7} . 0 ^11.16 ]
-4-eicosene derivatives, for example, the following formula (12)

Embedded image Heptacyclo [8.7.0.1 ^3.6 . 1
^10.17 . 1 ^12.15 . 0 ^2.7 . 0 ^11.16 ]
-4-eicosene derivatives. In particular, heptacyclo [8.7.0.1 ^3.6 . 1 ^10.17 .
1 ^12.15 . 0 ^{2 . 7} . 0 ^11.16] -4-eicosene dimethyl-substituted heptacyclo [8.7.0.1 ^3.6. 1
^10.17 . 1 ^{12 . 15} . 0 ^2.7 .
0 ^11.16 ] -4-eicosene.

Heptacyclo [8.8.0.1 ^2.9 . 1
^4.7 . 1 ^11.18 . 0 ^3.8 . 0 ^12.17 ] -5
A heneicosene derivative, for example, the following formula (13)

Embedded imageHeptacyclo [8.8.0.1 represented by^2.9. 1
^4.7. 1^11.18. 0 ^3.8. 0^12.17] -5
-Hen eicosene derivatives. In particular, heptacyclo [8.8.0.1^2.9. 1^4.7. 1
^11.18. 0^3.8. 0^12.17] -5-Henei
Kosen.

Heptacyclo [8.8.0.1 ^4.7 . 1
^11.18 . 1 ^13.16 . 0 ^{3. <8} . 0 ^12.17 ]
-5-heneicosene derivatives, for example, the following formula (14)

Embedded image Heptacyclo [8.8.0.1 ^4.7 . 1
^11.18 . 1 ^13.16 . 0 ^3.8 . 0 ^12.17 ]
-5-heneicosene derivatives. In particular, heptacyclo [8.8.0.1 ^4.7 . 1 ^11.18 .
1 ^13.16 . 0 ^{3. <8} . 0 ^12.17 ] -5-Heneicosene 15-methyl-heptacyclo [8.8.0.1 ^4.7 .
1 ^11.18 . 1 ^{1 3.16.} 0 ^3.8 .
0 ^12.17 ] -5-heneicosene trimethyl-substituted heptacyclo [8.8.0.1 ^4.7 .
1 ^11.18 . 1 ^{1 3.16.} 0 ^3.8 .
0 ^12.17 ] -5-Hen-eicosene.

Octacyclo [8.8.0.1 ^2.9 . 1
^4.7 . 1 ^11.18 . 1 ^{13.1 6.} 0 ^3.8 . 0
^12.17 ] -5-Docosene derivative, for example, the following formula (15)

Embedded imageOctacyclo [8.8.0.1 represented by^2.9. 1
^4.7. 1^11.18. 1 ^13.16. 0^3.8. 0
^12.17] -5-docosene derivative. In particular, octacyclo [8.8.0.1^2.9. 1^4.7. 1
^11.18. 1^{13. 16}. 0^3.8. 0^12.17]
-5-docosene 15-methyloctacyclo [8.8.0.1^2.9. 1
^4.7. 1^{11.1 8}. 1^13.16. 0^3.8. 0
^12.17] -5-Docosene 15-ethyloctacyclo [8.8.0.1^2.9. 1
^4.7. 1^{11.1 8}. 0^13.16. 0^3.8. 0
^12.17] -5-docosene.

Nonacyclo [10.9.1.1 ^4.7 . 1
^13.20 . 1 ^15.18 . 0 ^{2. 10} ． 0 ^3.8 . 0
^12.21 . 0 ^14.19 ] -5-pentacosene derivative, for example, the following formula (16)

Embedded image Nonacyclo [10.9.1.1 ^4.7 . 1
^13.20 . 1 ^15.18 . 0 ^2.10 . 0 ^3.8 . 0
^12.21 . 0 ^14.19 ] -5-pentacocene derivative. In particular, nonacyclo [10.9.1.1 ^4.7 . 1 ^13.20 .
1 ^15.18 . 0 ^{2 . 10} ． 0 ^3.8 . 0 ^12.21 .
0 ^14.19] -5-pentacosenoic trimethyl replacement Nonashikuro [10.9.1.1 ^4.7.
1 ^13.20 . 1 ^{1 5.18.} 0 ^2.10 . 0 ^3.8 .
0 ^12.21 . 0 ^14.19 ] -5-pentacocene.

Nonacyclo [10.10.1.1 ^5.8 .
1 ^14.21 . 1 ^16.19 . 0 ^{2 . 11} . 0 ^4.9 .
0 ^13.22 . 0 ^15.20 ] -6-hexacocene derivative, for example, the following formula (17)

Embedded imageNonacyclo [10.10.1.1] represented by^5.8. 1
^14.21. 1^{16.1 9}. 0^2.11. 0^4.9. 0
^13.22. 0^15.20] -6-Hexacocene derivative
body. In particular, nonacyclo [10.10.1.1^5.8.
1^14.21. 1^16.19. 0 ^2.1. 1.0
^4.9. 0^13.22. 0^15.20] -6-hexa
Kosen.

Other examples of cyclic olefins include
Can also be mentioned. 5-phenyl-bicyclo [2.2.1] hept-2-e
5-methyl-5-phenyl [2.2.1] hept-2-
Ene 5-benzyl-bicyclo [2.2.1] hept-2-e
5-tolyl-bicyclo [2.2.1] hept-2-ene 5- (ethylphenyl) -bicyclo [2.2.1] hep
To-2-ene 5- (isopropylphenyl) -bicyclo [2.2.
1] Hept-2-ene 5- (biphenyl) -bicyclo [2.2.1] hept-
2-ene 5- (β-naphthyl) -bicyclo [2.2.1] hept
-2-ene 5- (α-naphthyl) -bicyclo [2.2.1] hept
-2-ene 5- (anthracenyl) -bicyclo [2.2.1] hep
To-2-ene 5,6-diphenyl-bicyclo [2.2.1] hept-
2-ene cyclopentadiene-acenaphthylene adduct 1,4-methano-1,4,4a, 9a-tetrahydroph
Luorene 1,4-methano-1,4,4a, 5,10,10a-f
Xahydroanthracene 8-phenyl-tetracyclo [4.4.0.1^2.5.
1^7.10] -3-dodecene 8-methyl-8-phenyl-tetracyclo [4.4.
0.1^2.5. 1^{7. 10}] -3-dodecene 8-benzyl-tetracyclo [4.4.0.1^2.5.
1^7.10] -3-dodecene 8-tolyl-tetracyclo [4.4.0.1^2.5. 1
^7.10] -3-dodecene 8- (ethylphenyl) -tetracyclo [4.4.0.
1^2.5. 1^{7.1 0}] -3-Dodecene 8- (isopropylphenyl) -tetracyclo [4.
4.0.1.^2.5. 1 ^7.10] -3-dodecene 8,9-diphenyl-tetracyclo [4.4.0.1
^2.5. 1^7.10] -3-dodecene 8- (biphenyl) tetracyclo [4.4.0.1
^2.5. 1^7.10] -3-dodecene 8- (β-naphthyl) tetracyclo [4.4.0.1
^2.5. 1^7.10] -3-Dodecene 8- (α-naphthyl) -tetracyclo [4.4.0.1
^2.5. 1^7.10] -3-Dodecene 8- (anthracenyl) -tetracyclo [4.4.0.
1^2.5. 1^{7.1 0}] -3-dodecene (cyclopentadiene-acenaphthylene adduct)
Compound to which lopentadiene is further added 11,12-benzo-pentacyclo [6.5.1.1.
^3.6. 0^2.7. 0 ^9.13] -4-pentadecene 11,12-benzo-pentacyclo [6.6.1.1
^3.6. 0^2.7. 0 ^9.14] -4-Hexadecene 11-phenyl-hexacyclo [6.6.1.
1^3.6. 1^10.13. 0 ^2.7. 0^9.14] -4
-Heptadecene 14,15-benzo-heptacyclo [8.7.0.1
^2.9. 1^4.7. 1 ^11.17. 0^3.8. 0
^12.16-5-eicosene]

The copolymer (COC) is 50 to 22
Mol%, in particular from 40 to 22 mol%, of cyclic olefins and the balance of ethylene and up to 200 ° C., in particular 1
It preferably has a glass transition point (Tg) of 50 to 60 ° C.

The molecular weight of the copolymer is not particularly limited, but is 0.1 to 5 dl as measured in decalin at 135 ° C.
/ G of intrinsic viscosity [η], and its crystallinity is generally 10% or less, as measured by X-ray diffraction.
In particular, it is 5% or less.

The copolymer (COC) can be obtained by random polymerization of an olefin and a cyclic olefin in the presence of a vanadium catalyst or a metallocene catalyst known per se.

A suitable copolymer (COC) is available from Mitsui Petrochemical Co., Ltd. under the trade name APEL.

[Olefin Resin] The olefin resin to be the outer layer of the tube container of the present invention includes, for example,
Medium- or high-density polyethylene (LDPE, MDP
E, HDPE), isotactic polypropylene (PP), syndiotactic polypropylene, linear low density polyethylene (LLDPE), linear ultra low density polyethylene (LUDPE), ethylene-propylene copolymer, polybutene-1, ethylene- Butene-1 copolymer,
Propylene-butene-1 copolymer, ethylene-propylene-butene-1 copolymer, ethylene-vinyl acetate copolymer, ion-crosslinked olefin copolymer (ionomer),
Ethylene-acrylate copolymers, or a blend of two or more of these. Among these olefin resins, linear low-density polyethylene (L
LDPE) and linear ultra low density polyethylene (LUDP)
Low density polyethylene, including E), is preferred.

[0052] The density of the low density polyethylene, generally speaking, 0.910 to 0.940 g / cm ^3, in particular may be in the range of 0.914 to 0.925 g / cm ^3. The low-density polyethylene generally has a melt flow rate (ASTM D1238, 190 ° C.) of 2 g / g.
A resin of 10 minutes or less is preferred.

The low-density polyethylene described above may contain known additives such as pigments, fillers, antioxidants, lubricants,
Stabilizers, ultraviolet absorbers and the like can be blended according to a formulation known per se.

[Adhesive Layer] The adhesive strength between the outer layer of the olefin resin and the intermediate layer of the cyclic olefin copolymer and the adhesive strength between the cyclic olefin copolymer and the inner layer of the acrylonitrile resin are low. For the purpose of improving the adhesive strength, an adhesive resin layer is provided between the outer layer and the intermediate layer and between the intermediate layer and the inner layer.

As such an adhesive resin, an adhesive resin suitable for bonding an outer layer of an olefin resin and an intermediate layer of a cyclic olefin copolymer, and an adhesive resin between a cyclic olefin copolymer and an inner layer of an acrylonitrile resin. Although a suitable adhesive resin can be used separately, it is generally preferable to use a common adhesive resin.

Suitable examples of such adhesives include, but are not limited to, blends of low density ethylene-based and styrene-based copolymers.

The density of the low-density ethylene polymer used for the adhesive is generally 0.80 to 0.91 g / d.
cm ³ , especially in the range of 0.84 to 0.90 g / cm ³ , and is typically low density polyethylene (LDPE)
In addition, linear low density polyethylene (LLDPE) and linear very low density polyethylene (VLDPE) are used. Among these, VLDPE, which is a copolymer of ethylene and an α-olefin, is particularly suitable. Here, as the α-olefin, butene-1, pentene-1, hexene-
1, octene-1, decene-1, 4-methylpentene
Those having 4 to 8 carbon atoms such as 1 are preferably used. This copolymer has a branched chain derived from an α-olefin in the structure. Further, an acid-modified ethylene / α-olefin copolymer obtained by graphing the above-mentioned ethylene / α-olefin copolymer with maleic anhydride or the like can be used as an adhesive component.

On the other hand, examples of the styrene-based polymer used for the adhesive include a styrene-butadiene copolymer, a styrene-acrylonitrile copolymer, a styrene-acryl copolymer, and a polystyrene. Among these, styrene-acrylonitrile is also used. Copolymers are preferred.

The blend weight ratio of the low density ethylene polymer (i) to the styrene polymer (ii) is generally
(I): (ii) = 30: 70 to 80:20, the adhesion between the cyclic olefin-based copolymer and the acrylonitrile-based resin and the adhesion between the cyclic olefin-based copolymer and the olefin-based resin It is preferable in terms of properties.

Adhesive resins suitable for the purposes of the present invention are available from Mitsubishi Chemical Corporation under the trade names MODEC F502-F504.

[Tube Container and Manufacturing Method] The multilayer plastic tube container of the present invention is obtained by melting an olefin resin, a cyclic olefin copolymer, an acrylonitrile resin, and an adhesive resin with a corresponding extruder. The resin is the outer layer, the cyclic olefin-based copolymer is the intermediate layer, the acrylonitrile-based resin is the inner layer, and the adhesive resin is merged in the die head so as to be interposed between the intermediate layer and the outer layer and between the intermediate layer and the inner layer. It is manufactured by co-extrusion of the parison of the body followed by blow molding.

As the die head, a multilayer multiple die is used. The temperature of the die head varies depending on the type of the olefin resin, the cyclic olefin copolymer and the acrylonitrile resin used. The temperature is suitable for suppressing the drawdown tendency of the parison while preventing gelation of the cyclic olefin-based copolymer.

In the co-extrusion, the melt of the intermediate layer of the cyclic olefin copolymer is sandwiched in advance with a melt of the adhesive resin in a die to form a laminate melt. And the melt of the inner layer of the acrylonitrile resin, and the combined product can be extruded from the orifice of the die. At this time, the length of the confluence in the die is relatively short, and the temperature of the die head is maintained at a relatively low temperature, and the drawdown tendency is suppressed while the gelation of the cyclic olefin copolymer is prevented. It is effective in doing.

A molten multilayer parison extruded through an annular die orifice is blow molded in a split mold,
Pinch off the bottom to make a bottomed bottle. In addition, the bottle can be formed into a small-diameter bottle, the bottom of the bottle is cut, the contents are filled, and the open end is heat-sealed to form a tube container. Alternatively, a multi-layered pipe may be extruded and cut into a container body, and the mouth portion may be separately manufactured by injection molding, compression molding, or the like, and joined by melt bonding or the like to form a tube container.

[0065]

EXAMPLES The present invention will be described more specifically with reference to examples and comparative examples, but the present invention is not limited to the following examples. In addition, the measuring method in an example, and,
The evaluation method was performed according to the following procedure.

[Filling Contents and Filling Method] Turpentine oil, methyl salicylate, surfactant and water were each 70 wt.
%: 20 wt%: 10 wt%: 10 wt% W / O
(Water in oil) type emulsified product and its weight composition is 10wt%: 20wt%: 10wt%: 70wt%
O / W (oil in water) type emulsified product was prepared. Next, the nozzles of the various prototype bottles described in Examples and Comparative Examples were heat-sealed with an aluminum laminated film, the bottom was cut off, and the W / O (wa) was 70 g each from the bottom.
ter in oil) and O / W (oil in wa)
ter) type emulsified products were filled respectively. After filling the emulsified contents, the bottom was heat-sealed and stored in a 50 ° C constant temperature layer. The storage period was two weeks.

[Measurement of Adhesive Strength] Storage at 50 ° C. (2 weeks)
After removing the filling liquid from each tube, wash with water, air-dry,
The body was cut out into strips 15 mm wide. One of the cut sections was immersed in toluene to dissolve the COC layer, and the adhesive strength at the interface between the COC layer and the adhesive layer was measured by a tensile strength tester. The measurement conditions were a 100 g load cell, a distance between chucks of 30 mm, and a pulling speed of 300 mm / min.

[Hue Change of Innermost PAN Layer] An innermost PAN container prepared by dry blending 2 wt% and 10 wt% of titanium dioxide having an average particle diameter of 1.0 μm was evaluated. After heat sealing the nozzle part of the tube with aluminum laminated film,
Cut the bottom and 70 g of the test emulsion (O / W,
And W / O). Thereafter, the bottom was heat-sealed and stored in a constant temperature layer at 50 ° C. The storage period was two weeks. After storage, the contents were removed from the test bottle, washed with water, air-dried, and then the innermost surface layer was visually judged for cloudiness. Evaluation was performed by comparing the color of the innermost layer immediately after molding with the surface layer of the innermost layer after the storage test. A sample without any mark was marked with a circle. In addition, the innermost layer of titanium dioxide dry blend P
The AN container is whitened immediately after molding due to the inclusion of titanium dioxide.

[Moisture Barrier Property] The nozzles of the various test tubes described in Examples and Comparative Examples were heat-sealed with an aluminum laminated film, the bottom was cut off, 70 ml of distilled water was filled from the bottom, and the bottom was heat-sealed. . Each of the tubes containing distilled water was stored in a thermo-hygrostat at 40 ° C. and 30% RH. After storing for 6 months, the weight was measured, and the percentage of distilled water reduction was determined from a comparison between the initial weight of distilled water and the weight of distilled water after storage. Note that the limit value of the water reduction rate% was 3 wt%.

Example 1 (Resin) In the innermost layer, MI = 3.0 (ASTM D-12)
38) Polyacrylonitrile (PAN) was used.
Moreover, as an intermediate layer, the cyclic olefin content is 22 mol.
%: An ethylene cyclic olefin copolymer having a Mw of 130,000 was used. Furthermore, a low-density polyethylene (MI =
1.3) (ASTM D-1238) was used. In addition, an olefin-based PAN adhesive resin having MI = 1.0 (J1SK 6760) was used for bonding the innermost and outermost layers to the intermediate layer of the cyclic olefin-based copolymer resin.

(Molding) Using a multi-layer extruder consisting of four screw extruders, polyacrylonitrile (P
AN), direct blow molding of four kinds and five layers of the olefin adhesive resin as the adhesive layer, the ethylene cyclic olefin copolymer as the intermediate layer, the olefin adhesive resin as the adhesive layer, and the low density polyethylene resin as the outermost layer Was done. The cylinder temperature during molding was different for each of the four types of cylinders. In particular, the ethylene cyclic olefin copolymer resin was set at a temperature of 250 ° C. in a part of the cylinder. The total thickness is 450 μm, and the composition ratio of each layer is 11%: 5%: 10%: 5 from the inner layer to the outer layer.
%: A cylindrical tube having an internal volume of 180 ml, which is 69%, was prepared. Tables 1 and 2 show the evaluation results.

Example 2 The innermost layer had an average particle size of 1.0
MI containing 2% by weight of titanium oxide of μm =
3.0 (ASTM D-1238) polyacrylonitrile (PAN) was used. A tube similar to that in Example 1 was prepared for other layer configurations and a molding method. Tables 1 and 2 show the evaluation results.

Example 3 The innermost layer had an average particle size of 1.0
MI containing 10 wt% by weight of titanium oxide
= 3.0 (ASTM D-1238) polyacrylonitrile (PAN) was used. A tube similar to that in Example 1 was prepared for other layer configurations and a molding method. Tables 1 and 2 show the evaluation results.

Comparative Example 1 The innermost layer had an ethylene content of 4
A tube similar to that of Example 1 was prepared except that 4 mol% of an ethylene vinyl alcohol copolymer resin was used. Tables 1 and 2 show the evaluation results.

Comparative Example 2 A tube similar to that of Example 1 was prepared except that the innermost layer was made of low-density polyethylene (MI = 1.3) (ASTM D-1238). Tables 1 and 2 show the evaluation results.

[Comparative Example 3] The intermediate layer barrier material was an ethylene-vinyl alcohol copolymer, and a layer structure of three types and five layers consisting of low-density polyethylene / adhesive layer / ethylene-vinyl alcohol copolymer / adhesive layer / low-density polyethylene And the layer composition ratio is 11%: 5%: 10 from the inner layer to the outer layer.
A cylindrical tube having an internal volume of 180 ml and having a%: 5%: 69% was prepared. Example 1 was repeated except that the innermost layer was low density polyethylene. Tables 1 and 2 show the evaluation results.

COMPARATIVE EXAMPLE 4 MI = 3.0 (AS)
TM D-1238) polyacrylonitrile (PA
N) was used. The layer configuration changes from the inner layer to the outer layer.
%: 5%: 84% of PAN / adhesive layer / LDPE 3
A three-layer cylindrical tube having an inner volume of 180 ml was formed. Tables 1 and 2 show the evaluation results.

[0078]

[Table 1] O / W type emulsified product Peel strength of W / O type emulsified product Peel strength Moisture permeation amount (%) Example 1 1.5Kg 1.5Kg 1.5 Example 2 1.5Kg 1.5Kg 1 5.5 Example 3 1.5Kg 1.5Kg 1.5 Comparative Example 1 0.5Kg Delamination cannot be measured Comparative Example 2 0.5Kg Delamination cannot be measured Comparative Example 3 1.2Kg 1.0Kg 3.5 Comparative Example 4 1.5Kg 1.5Kg 8.0

[0079]

[Table 2] O / W type emulsified product Hue change after storage test immediately after molding of W / O type emulsified product Hue of inner surface material of emulsified test item Hue of inner surface material (visual judgment) Storage ¹⁾ Example 1 Transparent white × O Example 2 White and white O O Example 3 White and white O O Comparative example 1 − − − × Comparative example 2 − − − × Comparative example 3 − − − − × Comparative example 4 Transparent white × × 1 ): The preservability of the emulsified test product indicates that the COC layer was not dissolved and the water permeation amount was within 3 wt% in the content product preservation test described in Table 1.

[0080]

According to the present invention, the outer layer of linear olefin resin / adhesive layer / intermediate layer composed of cyclic olefin copolymer / adhesive layer / inner layer of acrylonitrile resin having high nitrile content By composing the container wall with the laminate,
Multi-layer plastic tube container with excellent preservability and chemical resistance of contents, especially when filled with W / O type or O / W type emulsion containing aromatic oxycarboxylic acid ester in oil phase. It is possible to provide a multi-layer plastic tube container for pharmaceuticals or quasi-drugs, which is excellent in the combination of the storage stability of a substance and the delamination resistance.

[Brief description of the drawings]

FIG. 1 is a sectional view showing a sectional structure of a vessel wall of a tube container of the present invention.

FIG. 2 is a side view of an example of the tube container of the present invention.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) B32B 27/32 B32B 27/32 EC B65D 35/10 B65D 35/10 A F-term (Reference) 3E065 BA11 BA14 BA40 BB03 4C086 DA17 MA01 MA22 NA03 ZA08 ZB11 4F100 AA21B AK03A AK03B AK03G AK04B AK04J AK06A AK08B AK08J AK27C AK27G AL01B BA03 BA07 BA10A BA10C BA15 CB00 EH20 Y17B20 JA17

Claims (5)

[Claims] 1. A laminate comprising a linear olefin resin outer layer / adhesive layer / intermediate layer composed of a cyclic olefin copolymer / adhesive layer / an inner layer of a high nitrile content acrylonitrile resin. Features Multi-layer plastic tube containers for pharmaceuticals or quasi-drugs 2. The pharmaceutical product or quasi-drug is a W / O or O / W emulsion containing an aromatic oxycarboxylic acid ester in an oil phase.
The tube container according to any one of the preceding claims. 3. The method according to claim 1, wherein the outer layer has a thickness of 5 to 600 μm, the intermediate layer has a thickness of 5 to 100 μm, the inner layer has a thickness of 5 to 100 μm, and the adhesive layer has a thickness of 5 to 100 μm. Or the tube container according to 2. 4. The tube container according to claim 1, wherein the inner layer is made of a resin composition containing titanium dioxide having a particle size of 0.01 to 10 μm. 5. The tube container according to claim 4, wherein 0.5 to 20 parts by weight of titanium dioxide is contained per 100 parts by weight of the resin.