JP7133938B2 - A package consisting of a plastic container and an exterior body - Google Patents

Description

TECHNICAL FIELD The present invention relates to a packaging body comprising a plastic container and an exterior body that are resistant to dew condensation inside the exterior body even when stored in an environment where dew condensation is likely to occur, such as a cold temperature condition, and are excellent in safety and hygiene.

For example, containers for packaging injections need to be designed appropriately to prevent the evaporation of water that constitutes the formulation, because of the need to maintain drug concentration and long-term storage. Specifically, it is required that the water vapor permeability is not more than a predetermined value in the water vapor permeability test in the plastic drug container test method. This moisture vapor permeability may be achieved by the primary packaging alone or by a combination of primary and secondary packaging.

Generally, the water vapor permeability of plastic containers for aqueous injections depends on the material and thickness of the resin used, and therefore has a certain degree of water vapor permeability. For this reason, it is effective to reduce the vapor permeability of the package by packaging with a laminated film having vapor barrier properties.

A plastic injection container (primary packaging) such as an infusion bag or bottle is filled with an aqueous injectable formulation, which is then sealed, and then placed in an external package (secondary packaging) such as a plastic pouch. Common. In particular, when the formulation has the property of being easily oxidized or decomposed in the presence of oxygen, as shown in Patent Document 1, an oxygen scavenger or the like and the formulation are filled in an exterior bag having gas impermeability. Encapsulation of sealed containers is a widely used means.

In addition, depending on the nature of the formulation, some formulations need to be stored in a refrigerated environment and allowed to stand at room temperature immediately before administration in order to ensure storage stability. At this time, depending on the difference between the temperature of the formulation in the primary package and room temperature and the humidity in the room environment, the water vapor that evaporates in the primary package and permeates the polymer membrane may condense in the secondary package. pointed out.

Condensation in the secondary packaging cannot be distinguished from liquid leakage from the primary packaging, and even if the primary packaging is sealed, it cannot be judged that the sterility of the drug product is ensured. cause problems. In addition, droplets generated by dew condensation can be a trigger for the propagation of bacteria and fungi, so it can be said that this is a serious quality problem from the viewpoint of ensuring the safety and hygiene of pharmaceuticals themselves.

A similar phenomenon is also seen in eye drop containers. For example, in Patent Document 2, the water vapor permeability balance between the primary packaging and the secondary packaging prevents evaporation of the filled liquid medicine and prevents dew condensation in the secondary packaging. A method is proposed. Specifically, the primary package alone has high water vapor permeability, and the product is designed to prevent water evaporation by housing it in the secondary package.

JP 2016-155864 A JP 2015-107322 A

According to the technique described in Patent Document 2, water evaporation from the primary packaging can be suppressed to a low level until the secondary packaging is opened, but the specified water vapor barrier performance is impaired when the secondary packaging is opened. As a result, a problem is pointed out that the evaporation rate of water during storage for repeated use is very high.

In addition, when applying the technology described in Patent Document 2 to injections such as infusion bags, if the primary packaging is designed to increase the water vapor permeability for the purpose of preventing dew condensation, the Japanese Pharmacopoeia "7.02 Plastic It deviates from the water vapor permeability test standard stipulated by the "Method of Testing Containers for Pharmaceuticals and Pharmaceuticals" and cannot be used as a water-based injection container.

The present invention addresses the above-mentioned problems, that is, it prevents changes in concentration due to evaporation of water in contents such as injections, and prevents dew condensation in the secondary packaging even during storage under refrigerated conditions or when the temperature is temporarily lowered. It is an object of the present invention to provide a packaging body composed of a plastic container and an exterior body that can be used.

In the present invention, it was found that the problem can be solved by suppressing the evaporation of water from the primary packaging and facilitating the permeation from the secondary packaging to the outside, thereby suppressing the increase in the water vapor pressure inside the secondary packaging. rice field.

The above problems can be solved by the present invention described below.
That is, the first invention is a combination of an airtight plastic container for containing water or an aqueous solution as a content, and an exterior body containing the plastic container and having a film portion sealed. A packaging body, wherein the plastic container and the exterior body do not have hygroscopicity, and the storage part for storing the contents of the plastic container is kept at a temperature of 40 ° C. and a relative humidity of 90% according to the method of JIS K7129. is in the range of 0.01 to 5 (g/m ² · 24h), and the film portion of the exterior body is measured at a temperature according to the method of JIS _K7129 . The water vapor transmission rate (WVTR _O ) measured in an environment of 40 ° C. and 90% relative humidity is within the range of 0.1 to 100 (g / m ² · 24 h), and each water vapor transmission rate is The relationship WVTR _O )−(WVTR _I )>0 is satisfied, and the volume of air present between the exterior body and the plastic container is equal to the volume of the contents housed in the plastic container. 3 times or less, and the inside of the outer package is at normal pressure, and the contents are stored in a temperature environment of 0 to 10 ° C., or 10 ° C. to normal temperature A package comprising a plastic container and an exterior body, characterized in that dew condensation does not occur even when temporarily placed in a temperature environment of 0 to 10° C. in applications stored within the range of .

In the second invention, the plastic container is in the form of an infusion bag, blow container, ampoule, or vial.
In a third invention, the contents are pharmaceuticals.
In a fourth invention, the pharmaceutical is an injection.
In the fifth invention, the injection contains at least one of plasma derivatives, enzymes, blood coagulation fibrinolytic factors, hormones, vaccines, interferons, erythropoietins, cytokines, antibodies, and fusion proteins, The plastic container includes an aseptic filling bag container and a stopper.

According to the present invention, it is possible to prevent concentration changes due to moisture evaporation of the contents of injections and the like, and to prevent dew condensation from occurring in the secondary packaging even during storage under refrigerated conditions or when the temperature is temporarily lowered. can be done.

It is sectional drawing which shows the outline of a package.

The present invention will be described below based on preferred embodiments.
FIG. 1 is a cross-sectional view showing the outline of the package of this embodiment.

A packaging body 30 of this embodiment is composed of a plastic container 10 having a containing portion 12 containing a content 11 and an exterior body 20 containing the plastic container 10 . The plastic container 10 and the exterior body 20 do not have hygroscopicity.

The content 11 is water or an aqueous solution, and the plastic container 10 is airtight. Here, the term "airtightness" refers to the property of a container that prevents solid or liquid foreign matter from entering from the outside of the plastic container 10 and prevents loss, efflorescence, deliquescence, or evaporation of the contents. It is sufficient if it has the property of an "airtight container" defined in the general rules of the other party.

In the Kojien dictionary, airtightness is defined as ``not allowing gas to pass through, or being sealed against gas,'' whereas in the Japanese Pharmacopoeia, ``a container that does not allow gas to enter'' is defined as a ``sealed container. "Sealed containers" include glass containers, double-sided aluminum blister packs, and extruded metal tubes. The plastic container 10 of this embodiment does not necessarily have to be a "gas-impermeable container".

The plastic container 10 is not particularly limited, but is preferably in the form of an infusion bag, blow container, ampoule, or vial. The plastic container 10 may have an outlet 13 that can be sealed with a rubber stopper or the like. Contents 11 may be removed without opening container 12 by inserting the needle of a syringe into outlet 13 . For visual confirmation of the contents 11, it is preferable that at least a portion of the containing portion 12 is transparent.

The contents 11 include pharmaceuticals such as injections. As will be described later, this is suitable when the contents 11 require cold storage. Examples of such injections include those containing one or more of plasma derivatives, enzymes, blood coagulation fibrinolytic factors, hormones, vaccines, interferons, erythropoietins, cytokines, antibodies, and fusion proteins. . A plastic container containing an injection or the like preferably includes an aseptic filling bag container and a stopper.

The storage portion 12 of the plastic container 10 of the present embodiment has a water vapor transmission rate (WVTR _I ) measured in an environment of 40° C. and 90% relative humidity according to the method of JIS K7129, which is 0.01 to 5 (g/ m ² ·24 h). Generally, it is difficult to reduce the water vapor permeability of plastics as compared to metals and glass.

The exterior body 20 is in a state where the film portion 22 is sealed, and the space between the film portion 22 and the plastic container 10 is filled with air 21 . The film portion 22 of the exterior body 20 has a water vapor transmission rate (WVTR _O ) of 0.1 to 100 (g/m ² · 24 h) measured in an environment with a temperature of 40 ° C. and a relative humidity of 90% according to the method of JIS K7129. ). It is preferable that the film portion 22 has a substantially uniform distribution of water vapor transmission rate and that the film portion 22 has no holes.

When the exterior body 20 is composed of two or more film portions 22, the water vapor permeability of each film portion 22 may be the same or different. The value obtained by averaging the water vapor permeability according to the above should be within the above range. For example, if a film with a permeation area of A1 and _a water vapor permeability of _WVTR1 and a film with a permeation area of _A2 and a water vapor permeability of _WVTR2 are used on different surfaces of the exterior body, the total permeation area ( m ² ) is (A ₁ +A ₂ ), and the total amount of water vapor permeation per 24 hours (g/24h) is (A ₁ ·WVTR ₁ +A ₂ ·WVTR ₂ ), so the average water vapor transmission rate is It is obtained as (A ₁ ·WVTR ₁ +A ₂ ·WVTR ₂ )/(A ₁ +A ₂ ).

Examples of the plastics constituting the plastic container 10 and the exterior body 20 include one or more of polyester resins, nylon resins, polycarbonate resins, polypropylene resins, polyethylene resins, cyclic polyolefin resins, polystyrene resins, fluororesins, elastomers, and the like. be done. These plastics can be used for containers as films, sheets, tubes, molded articles, and the like. In the case of lowering the water vapor permeability of plastic, a metal such as aluminum or a metal oxide such as silica or alumina may be laminated with the plastic as a metal foil or vapor deposition film. The water vapor transmission rate of plastics can be adjusted by selection, thickness, combination of materials, and the like. Lamination methods include dry lamination, extrusion lamination, heat lamination, coextrusion, multilayer blow molding, lamination injection molding, coating, and the like.

In addition, the packaging body 30 of the present embodiment is used for storage in a temperature environment of 0 to 10° C. with the air 21 inside the exterior body 20 at normal pressure and the contents 11 accommodated. Alternatively, it has the property of not causing dew condensation even when it is temporarily left in a temperature environment of 0 to 10°C in applications where it is stored in the range of 10°C to room temperature. Here, the normal pressure means equal to the atmospheric pressure without pressurization or decompression. It is sufficient that the film portion 22 forming the exterior body 20 can be deformed according to changes in the atmospheric pressure, and that there is no pressure difference between the air 21 inside the exterior body 20 and the outside atmosphere. Further, normal temperature means 20 to 25° C., considering the range of temperatures (20° C., 23° C., 25° C.) of standard conditions defined in JIS Z8703 (standard conditions of test locations).

At a low temperature of 0 to 10°C, the amount of water vapor per ^{cubic meter of air is 4.8 to 9.3 g/m 3 .} / ^m3 . However, the preservation state of this embodiment is not limited to 100 RH% relative humidity of the external atmosphere. Since the storage temperature is 0° C. or higher, freezing of the moisture in the package 30 including the moisture in the contents 11 is suppressed. Further, if the storage temperature of the package 30 is below room temperature, that is, within the range of 0 to 10° C. or 10° C. to room temperature, the airtightness of the plastic container 10 is maintained. The lower limit of the storage temperature is not limited to 0°C or 10°C, and the lower limit temperature can be set to 0°C or higher or 10°C or higher. The upper limit of the storage temperature is not limited to room temperature (20 to 25° C.) or 10° C., and the upper limit temperature can be set to room temperature or lower (25° C. or lower, 20° C. or lower) or 10° C. or lower. The low temperature of 0 to 10° C. during storage of the package 30 may be constant, continuous, or temporary, and may be intentional or accidental.

The plastic container 10 can be put in and taken out of the exterior body 20 , and air 21 exists between the exterior body 20 and the plastic container 10 . The volume of this air 21 is within three times the volume of the contents 11 housed in the plastic container 10 . Considering the volume change of the gas due to temperature, it is preferable that the volume of the air 21 is within three times the volume of the content 11 at 0 to 10°C. The volume of the contents 11 is preferably 20 mL or more, for example. Also, "within 3 times" may be "within 2 times".

Further, the water vapor transmission rate (WVTR _I ) of the housing portion 12 and the water vapor transmission rate (WVTR _O ) of the film portion 22 satisfy the relationship of (WVTR _O )−(WVTR _I )>0. That is, WVTR _O must be greater than WVTR _I. Furthermore, it is preferable that the difference or ratio between (WVTR _O ) and (WVTR _I ) is within a predetermined range.

Next, the action of the package 30 that satisfies the above conditions will be described.
The inside of a plastic container 10 filled with water or an aqueous solution as the content 11 is wet. Moreover, the interior of the exterior body 20 housing the plastic container 10 is relatively dry. Therefore, there is a difference in water vapor pressure between the inside and outside of the plastic container 10 . The vapor pressures on both sides of the container 12 of the plastic container 10 try to reach equilibrium, and the moisture inside the plastic container 10 moves into the air 21 between the plastic container 10 and the exterior body 20 as water vapor.
However, if the film portion 22 forming the exterior body 20 has a low water vapor permeability (high water vapor barrier property), the water vapor that has moved to the outside of the plastic container 10 will be confined inside the exterior body 20 . Therefore, the water vapor pressure inside the exterior body 20 increases to a certain level over time. Furthermore, at a low temperature of 0 to 10° C., the saturated water vapor pressure is lowered, so the portion exceeding the pressure is condensed and forms water droplets to condense.
Therefore, in order to prevent dew condensation inside the exterior body 20 and outside the plastic container 10, the water vapor barrier properties of the exterior body 20 should be lowered to continuously move water vapor from the interior of the exterior body 20 to the outside. is required. Therefore, when the water vapor transmission rate (WVTR _I ) of the plastic container 10 and the water vapor transmission rate (WVTR _O ) of the exterior body 20 are compared, the relationship WVTR _I <WVTR _O must be established. Packaging at a low temperature of 0 to 10 ° C. is achieved by increasing the water vapor transmission rate of the exterior body 20, moving water vapor to the outside of the exterior body 20, and suppressing the increase in water vapor pressure in the air 21 inside the exterior body 20. Even if the saturation vapor pressure in the body 30 drops, it is possible to prevent condensation.

Although the present invention has been described above based on preferred embodiments, the present invention is not limited to the above-described embodiments, and various modifications can be made without departing from the gist of the present invention.

EXAMPLES The present invention will be specifically described below with reference to examples.

[Film Formation of Primary Packaging Sheet and Formation of Bag Container]
(1-1) Vapor-phase metallocene polyethylene “Harmolex (registered trademark)” manufactured by Nippon Polyethylene Co., Ltd. and having a density of 0.908 g/cm ³ and a peak melting temperature of 120° C. was produced using a T-die extrusion film-forming machine. A polyethylene (PE) sheet with a thickness of 230 μm was formed using the as a raw material.
(1-2) The above PE sheet is combined with a 12 μm-thick silica-deposited biaxially oriented polyester film ("Tech Barrier (registered trademark) L" manufactured by Mitsubishi Chemical Corporation) and a polyurethane adhesive manufactured by Mitsui Chemicals, Inc. " Takelac (registered trademark)” was laminated by a dry lamination method to obtain a laminate sheet.
(1-3) After curing the adhesive, two laminate sheets were placed facing each other with the PE surface facing inward, and manufactured by injection molding using HDPE ("Hi-Zex (registered trademark)" manufactured by Prime Polymer Co., Ltd.) as a raw material. The outer periphery was heat-sealed together with the discharge port, and a bag container having an inner dimension of the pouch portion of 140 mm×100 mm was manufactured.
(1-4) The water vapor transmission rate (WVTR) value of the laminate sheet measured under an environment of 40° C. and 90% relative humidity according to the method of JIS K7129 was 0.2 (g/m ² 24 h). rice field.
(1-5) In addition, without laminating the silica-deposited biaxially stretched polyester film, a PE sheet with a thickness of 230 μm was made into a bag container shape in the same manner as in (1-3), and the thickness of the PE sheet was changed. Then, as shown in Table 1, various primary packages having different water vapor permeability were produced.

[Film Formation of Secondary Packaging Sheet and Formation of Secondary Packaging Pouch]
(2-1) Using gas-phase method metallocene polyethylene "Harmolex (registered trademark)" manufactured by Japan Polyethylene Co., Ltd. with a density of 0.908 g/cm ³ and a melting peak temperature of 120°C by an air-cooling inflation film forming method as a raw material, A polyethylene (PE) film with a thickness of 40 μm was obtained.
(2-2) The above PE film is combined with a 12 μm-thick biaxially oriented polyester film ("Superneal (registered trademark)" manufactured by Mitsubishi Chemical Corporation) and a polyurethane adhesive "Takelac (registered trademark)" manufactured by Mitsui Chemicals, Inc. Trademark)” was laminated by a dry lamination method to obtain a laminate film.
(2-3) After the adhesive is cured, the two laminate films are placed facing each other with the PE surface facing inward, the three outer peripheries are heat-sealed, the remaining one is open, and the outer size of the pouch is 240 mm. A secondary packaging pouch having a size of ×160 mm and a heat-sealed width of 10 mm was produced. The WVTR value of this secondary packaging pouch was 5.1 (g/m ² ·24h).
(2-4) In addition, as the biaxially stretched polyester film of (2-2), a barrier film ("Tech Barrier (registered trademark) L" manufactured by Mitsubishi Chemical Corporation) having one side surface subjected to silica deposition treatment is vapor-deposited. A laminate film was prepared by combining the laminate film with the side to be the bonding surface. The WVTR value of this laminate film was 0.27 (g/m ² ·24h). A secondary packaging pouch was produced in the same manner as in (2-3).

[Test method for primary package]
A bag container was filled with 100 mL of water as a content and sealed with a rubber stopper to prepare a primary package. JP17 water vapor permeability (% ) was measured.

The WVTR and JP17 water vapor permeability values for each primary packaging container are shown in Table 1. When the WVTR value of the primary packaging container exceeds 5 (g/m ² ·24h), the JP17 water vapor permeability (%) deviates from the standard and becomes non-compliant. The standard value for water vapor permeability of plastic containers for aqueous injections is 0.20% or less.

<Experiment 1>
A specimen was prepared by housing the above primary package in a secondary package pouch and heat-sealing the opening in the same manner as the three-sided sealing portion. The prepared sample was left in an oven at a temperature of 30° C. and a relative humidity of 70% for 2 weeks, and then stored in a refrigerator at 5° C. for another 2 weeks. After a predetermined period of time, the specimen was taken out from the refrigerator and visually observed for the presence or absence of dew condensation in the secondary packaging pouch. The evaluation criteria were "○" when no dew condensation occurred in the secondary packaging, "X" when dew condensation occurred and water droplets were observed, and "Δ" when water droplets were slight.
After the test, in order to determine the volume of air present in the secondary packaging pouch, the air inside the secondary packaging pouch was extracted using an injection needle and a plastic syringe without opening the exterior, and the air volume was calculated from the memory of the syringe. Calculated. The air volume for each specimen is listed in Table 2 as well.

Table 2 shows the results of Experiment 1 using a combination of the primary packaging shown in Table 1 and the secondary packaging.

As shown in Table 2, it was found that when the WVTR value of the primary packaging is lower than the WVTR value of the secondary packaging, condensation inside the packaging system stored under refrigerated conditions can be prevented.
In addition, it is considered possible to set the liquid volume of the content to 50 mL or 200 mL, for example.

<Experiment 2>
Specimens were prepared by housing the above primary packages A to G in a secondary package pouch, and heat-sealing the opening in the same manner as the three-sided sealing. After storing the prepared specimen in a cardboard box, it was transported one-way between Tokyo and Osaka by a room-temperature truck, together with a data logger for temperature recording. Analysis of data logger recordings showed 11 hours of time in the range of 2-10°C. After standing for 1 hour in a room at 23°C (relative humidity 50%) at the destination, the package was opened, and the presence or absence of dew condensation in the secondary package was visually observed and recorded according to the same evaluation criteria as in Experiment 1.
Table 3 lists the results of Experiment 2.

The results of Experiment 2 showed similar trends to those obtained in Experiment 1. It has been suggested that condensation may similarly occur if a product intended for room temperature storage is temporarily exposed to cold temperatures during transport, as is the case when the product is stored under refrigerated conditions and then removed to a room temperature environment. It has been shown that there is a need for proper packaging design according to the present invention.

DESCRIPTION OF SYMBOLS 10... Plastic container, 11... Contents, 12... Accommodating part, 13... Discharge port, 20... Exterior body, 21... Air, 22... Film part, 30... Package body.

Claims (5)

A package consisting of a combination of an airtight plastic container for containing water or an aqueous solution as a content and an exterior body containing the plastic container and having a film portion sealed,
The plastic container and the exterior body do not have hygroscopicity,
The storage part for storing the contents of the plastic container has a water vapor transmission rate (WVTR _I ) measured in an environment of 40 ° C. and 90% relative humidity according to the method of JIS K7129 of 0.01 to 5 (g / m ² · 24 h) within the range,
The film portion of the exterior body is made of plastic only, and has a water vapor transmission rate (WVTR _O ) of 0.1 to 100 measured under an environment of 40°C temperature and 90% relative humidity according to the method of JIS K7129. (g / m ² · 24 h) within the range,
Each water vapor transmission rate satisfies the relationship of (WVTR _O )−(WVTR _I )>0,
Furthermore, the volume of air existing between the exterior body and the plastic container is within three times the volume of the contents housed in the plastic container,
In addition, the interior of the exterior body is normal pressure, and the content is stored in a temperature environment of 0 to 10 ° C., or stored in the range of 10 ° C. to room temperature. A package comprising a plastic container and an exterior body, characterized in that it does not cause dew condensation even when it is temporarily placed in a temperature environment of 0 to 10°C in the application. 2. The package according to claim 1, wherein the plastic container is in the form of an infusion bag, a blow container, an ampoule, or a vial. 3. A packaging body comprising a plastic container and an exterior body according to claim 1 or 2, wherein said contents are pharmaceuticals. 4. The package according to claim 3, comprising a plastic container and an outer package, wherein the drug is an injection. The injection contains at least one of plasma derivatives, enzymes, blood coagulation fibrinolytic factors, hormones, vaccines, interferons, erythropoietins, cytokines, antibodies, and fusion proteins, and the plastic container is sterile. 5. A package comprising a plastic container and an outer package according to claim 4, comprising a filling bag container and a stopper.

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