JPH07231929A - Medical fluid-containing container - Google Patents

Abstract

PURPOSE:To prevent the deterioration of a medical fluid by charging the medical fluid in a container composed of material quality high in gas barrier properties of oxygen or carbon dioxide and hardly affected by moisture. CONSTITUTION:A medical fluid-containing container is obtained by thermally molding a packing material, at least a part of which is formed from layers containing a thermotropic liquid crystal polyester layer, including a soft plastic container.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a container containing a medical liquid, which prevents deterioration of the contained medical liquid due to oxygen, carbon dioxide gas, etc. and is less affected by water. More specifically, it relates to a gas barrier blister packaging material. It is about improvement.

[0002]

2. Description of the Related Art Among infusion solutions, blood preservation solutions and other medicinal solutions, there are some which are easily deteriorated by air, such as amino acid preparations and fat emulsions. It is also important to keep the water content in the medicinal solution as constant as possible.

On the other hand, as the material of the container for containing and storing the medicinal liquid, from the viewpoints of lightness, impact resistance and easy handling, soft polyvinyl chloride, polyethylene and ethylene vinyl acetate copolymer are used as the material. Plastics are often desired, and some measures are necessary because these polymers do not have sufficient barrier properties to gases, especially oxygen.

As a general measure that has been or has been attempted in the past, a general method is to wrap the drug solution container with an outer wrapping material having a gas barrier property.

Of these, so-called blister packaging is one of the general-purpose means, and a sheet or film containing a gas barrier material layer is thermoformed.
Then, it is molded into a fixed shape, and the medicinal solution container is sealed therein.

However, the problem here is the selection of the "gas barrier material", which is a generally known gas barrier material (a) aluminum foil, (b) polyvinylidene chloride, (c) ethylene vinyl alcohol copolymer,
(D) Considering the thermoforming including the ceramic coating film, none of them is sufficiently satisfactory for the following reasons.

(A) Aluminum foil: A large barrier property against most gases such as oxygen, carbon dioxide and water vapor.

The disadvantage is that thermoforming is impossible and incineration is not possible.

(B) Polyvinylidene chloride: Almost exhibits a gas barrier property in the room temperature region and can be thermoformed.

Since it contains chlorine, it remains a problem during disposal.

(C) Ethylene vinyl alcohol copolymer: Shows excellent barrier properties against oxygen and carbon dioxide in the room temperature region and has good thermoformability.

However, since it is hygroscopic, it is sensitive to water, has a poor barrier property in a high humidity atmosphere, and is not necessarily suitable for storing a substance containing a large amount of "water" such as a medicinal solution. . In order to avoid the influence of moisture, there is a method of laminating it with a sheet having low moisture permeability such as polypropylene, or sandwiching it with a film containing a hygroscopic agent, but the polypropylene sheet needs to be thick and contains a hygroscopic agent. There is a limit to the performance when using the film.

(D) Ceramic coat film: A typical example is a polyethylene terephthalate film vapor-deposited with silicon oxide, which shows barrier properties second only to aluminum foil and has a smaller temperature dependency than (b) and (c). . Also, since the ash content is small, there are few problems in disposal.

However, since "ceramic" cannot be stretched during thermoforming, it is unavoidable to adopt a method of coating (vapor deposition) after thermoforming, which complicates the process and apparatus and lowers the productivity.

In addition to (b) and (d), polymers such as polymethaxylylene adipamide and polyethylene-2,6-naphthalate are also called thermoformable gas barrier packaging materials, but sufficient gas is used. To obtain the barrier property, it is necessary to make the film (sheet) thick.

[0016]

SUMMARY OF THE INVENTION The present invention has been made to solve the above-mentioned problems in a gas-barrier blister packaging material for preventing alteration of the contained medical liquid.

[0017]

The gist of the present invention is a container comprising a sealed soft plastic container (A) for containing a medicinal solution and a sealed packaging material (B) containing (A). , (B) is at least partially formed of a sheet or film containing a thermotropic liquid crystal polyester layer and is thermoformed, which is a container containing a medicinal solution.

That is, the thermotropic liquid crystal polyester has extremely good gas barrier properties as an organic polymer and relatively excellent thermoformability, and sufficiently satisfies the performance required for a gas barrier blister material for pharmaceutical liquids. is there.

In the present invention, a soft plastic container (A) used as an encapsulating material (a material that directly contacts a liquid medicine)
Is usually a known polymer, and polyvinyl chloride containing di (2-ethylhexyl) phthalate, di-n-decylphthalate, butyryltri-n-hexyl citrate as a plasticizer (which should be avoided as much as possible from the present invention). Of course), high pressure low density polyethylene, ethylene vinyl acetate copolymer, polypropylene, polybutene-
It is formed from a polymer such as 1.

Next, the packaging material (B) which is an outer packaging material will be described.

The thermotropic liquid crystal polyester (hereinafter referred to as LCP) in the present invention is a general term for polyesters that form a melt liquid crystal in the process of melting, and the basic structure of a typical example is represented by the following general formula (1) )-(3). Note that x ₁ , x ₂ , x ₃ , y ₁ , y ₂ , y ₃ , and z ₁ in the following formulas are natural numbers.

[0022]

[Chemical 1]

[0023]

[Chemical 2]

[0024]

[Chemical 3]

All of these show good gas barrier properties, but in view of thermoformability, flexible ones are preferable.
In particular, those containing an aliphatic component such as (3) are preferable, and x
The ratio of ₁ and y ₁ is 40:60 to 9 (in terms of molar component).
0:10, more preferably 50:50 to 80:20 and 1
Heat distortion temperature at 8.6 kg / cm ² (ASTMD-
648) is 60 to 210 ° C, more preferably 70 to 20 ° C.
A temperature of about 0 ° C is preferable (the higher the heat distortion temperature, that is, the higher the content of the paraoxybenzoic acid component, the better the gas barrier property tends to be, but the thermoformability should be reduced). .

The manufacturing method of LCP is, for example, Jackson, WJ, Kuhfa
ss, JF: J.Polym, Sci.Polym, Chem, Ed., 14 , 2043
(1976), copolymerization of paraacetoxybenzoic acid in the presence of polyethylene terephthalate gives a (3) type LCP.

Further, the dicarboxylic acid component is phenyl esterified or the diol component is acetated, and melt polycondensation or solution polycondensation is carried out to produce LCPs of the types (1) and (2).

In the above general formulas (1) to (3), it goes without saying that the LCP may be either a random type copolyester or a block type copolyester.

The wrapping material (B) in the present invention is characterized in that "at least a part" is formed of a sheet or film "containing a layer of LCP" and thermoformed, where "of LCP" is used. The term "including a layer" means that the sheet or the film is composed of an LCP layer alone and is laminated with a layer of another polymer such as polyethylene, polypropylene, ethylene vinyl acetate copolymer, polyester (polyester having no liquid crystallinity), or polyamide. It means that they may be combined.

In general, the latter multi-layer type is used for the purpose of maintaining strength, improving thermoformability, and improving sealing property. Further, in the above, "at least a part" means that the packaging material (B) is formed of a part of a sheet or film containing a layer of LCP, or only a part of the packaging material (B) is thermoformed. In some cases, the following form is recommended for practical use.

That is, the LCP layer-containing sheet or film is thermoformed into an appropriate shape to obtain a bottom material, and after containing the container (A), the non-thermoformed gas barrier sheet or film is used as a top material, and the bottom material is formed. It is a method of sealing the top material with the top material.

Here, the gas barrier sheet or film of the top material may be, of course, an LCP layer-containing sheet or film, but may be one such as the above-mentioned ceramic coat film.

In the present invention, for the purpose of distinguishing between "sheet" and "film", a sheet having a thickness of 0.25 mm or more is called a sheet and a sheet having a thickness of less than 0.25 mm is called a film.

The drug solution-containing container of the present invention can be manufactured by applying a generally known method. First, the soft plastic container (A) is formed into a sheet by a T-die method, an inflation method, a blow method, etc., and heat-sealed to attach members (injection of liquid medicine, discharge port, rubber stopper, tube, etc.), liquid medicine. It is manufactured by appropriately injecting, sterilizing, and the like.

The thickness of the sheet of the container is generally 0.1 to 1 mm, more preferably 0.2 to 0.7 mm.

The LCP-containing sheet or film constituting (B) is also manufactured by using the same method or laminating method as in (A).

The thickness of the sheet or film varies depending on the required gas barrier properties, strength, rigidity, etc.
In the case of a CP single layer, 0.03 to 0.8 mm, more preferably 0.05 to 0.5 mm, and in the case of a multilayer structure of the LCP layer and another polymer layer, the LCP layer is one layer. Per 0.01 to 0.3 mm, more preferably 0.
015 to 0.2 mm and overall thickness is 0.08 to 3.0 m
m, more preferably about 0.1 to 2.5 mm.

Thermoforming of the LCP-containing sheet or film is also carried out by generally known pressure molding, vacuum molding or the like.

The temperature varies depending on the type of LCP, the type of other polymer, the thickness of the sheet or film, and the like, but the temperature is in the range of 100 to 250 ° C.

The squeezing limit (ratio of height to width or diameter of molded product) is preferably 1.0 or less, more preferably 0.8 or less.
This is because so-called "deep drawing" is often difficult in LCP.

It is possible to wrap (A) with (B) either before or after sterilization of (A).

In the present invention, the atmosphere between (A) and (B) is arbitrary (vacuum (reduced pressure), nitrogen, etc., depending on the application and requirements. If necessary, an oxygen absorber may be added between (A) and (B).

The medicinal liquid targeted by the present invention includes the above-mentioned amino acid preparation, fat emulsion, physiological saline solution, electrolyte solution,
Examples include dextran preparations, mannitol, sugar preparations, and the like.

[0044]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto.

(Examples 1 and 2, Comparative Example 1) (1) Container and Film Container (A) for directly containing the medicinal liquid and the same: Density 0.92 g / cm ³ containing hexene-1 as a copolymerization component A linear low-density polyethylene bag (made of a sheet having a thickness of 0.3 mm, having a flat shape of 40 × 180 × 130 mm, and a high-density polyethylene tube having a rubber plug attached to one end thereof. (A fixed drainage port is fixed), 500 ml of an infusion solution consisting of an aqueous solution containing about 10 wt / v% of amino acid was incorporated and subjected to high-pressure steam sterilization treatment at 110 ° C. for 20 minutes.

Sheet or film containing LCP layer: Table 1 shows the composition and properties. Oxygen gas permeability is MOC
The measurement was performed under the condition of 35 ° C. × 90% RH using an ON device.

Other sheets or films: Table 2 shows the composition and properties. The oxygen gas permeability was measured by using a MOCON device in the same manner as in, under the condition of 35 ° C. × 90% RH. .

Thermoforming of sheet or film: The sheet or film prepared in or is subjected to pressure molding (temperature 170 to 180 ° C., time 5 seconds), and length 190 m.
A rectangular parallelepiped bottom (blister) having a size of m × width 135 mm × depth 42 mm was produced.

Preparation of container containing drug solution: The container containing drug solution (A) was placed at the bottom of the container, or the sheet or film was used as the top material for heat sealing. The sealing conditions are a sealing temperature of 200 to 220 ° C. and a sealing time of 5 seconds.

Aging test of container containing medicinal liquid: Three kinds of containers containing medicinal liquid (see Table 3) were tested at 35 ° C. × 90% R
It was left under an atmosphere of H for 40 days.

[0051]

[Table 1]

[0052]

[Table 2]

(2) Experimental results (see Table 3) The thermoforming was good in both Examples and Comparative Examples, and was performed well.

As shown in Table 3 for the observation results of the samples obtained in the time-dependent change test, in the use of the packaging material (B) containing the LCP layer, the yellow color of the medicinal liquid (amino acid preparation) was observed even after standing for 40 days. It is stable without any change.

On the other hand, when ethylene vinyl alcohol was used as the gas barrier material (comparative example), oxygen gas permeability was large under the influence of humidity, and yellowing of the amino acid preparation was observed.

[0056]

[Table 3]

[0057]

EFFECTS OF THE INVENTION As described above, the container of the present invention containing a medicinal solution is produced by skillfully utilizing the gas barrier performance and thermoformability of LCP, and exerts a great effect on stable storage of the medicinal solution. . In addition, the structure is versatile and has high industrial value.

Claims (1)

[Claims] 1. A container comprising a sealed soft plastic container (A) containing a medicinal solution and a sealed packaging material (B) containing (A), wherein at least a part of (B) is a thermostat. A container containing a medicinal solution, which is formed of a sheet or film containing a tropic liquid crystal polyester layer and is thermoformed.