JPH10155875A - Freeze dried product formed by using plastic container and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To make handling safe, discarding by incineration easy, freeze drying rapid and easy and long-term preservation possible by thinly forming at least the base of a plastic container and hermetically covering the thin walls with a gas permeation preventive member. SOLUTION: The bottom 2A and side part 2B of the plastic container 2 are partly formed thin and the thin walls 2A, 2B are hermetically covered with the gas permeation preventive member 4. The thin walls 2A, 2B are formed at thin as in a range of 10 to 3000μm. This plastic container 2 is formed by injection molding of polypropylene (PP). The gas permeation preventive member 4 is formed of the molding of the PP and aluminum is deposited by evaporation on its outside surface to impart a gas barrier property to the container. The occurrence of discoloration in freeze dried matter 7 is prevented by this constitution even after lapse of one month.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a freeze-dried product such as a medical drug and a method for producing the same, and more particularly, to a freeze-dried product using a plastic container suitable for incineration and disposal and a method for producing the same. It is about.

[0002]

2. Description of the Related Art Generally, freeze-dried products such as medical drugs are contained in glass vials. Glass is highly transparent and has the property of not transmitting gas, water vapor, etc. at all.
The freeze-dried product contained in the vial is not likely to be degraded by external oxygen or water vapor. On the other hand, some plastics have poor permeability to gas, water vapor, and the like, but if the thickness is not considerably large, gas, water vapor, and the like can pass. Therefore, when a plastic container is used as a freeze-dried product, a considerable thickness is required for the container wall. For this reason, glass vials are currently mainly used for medical purposes. However, such vials are easily damaged during handling, and incineration requires a great deal of trouble.

[0003]

However, when a plastic container is used as a container for storing a freeze-dried product, the following problems occur. First, in order to increase the gas permeability of a plastic container, the thickness of the container wall must be increased, or a resin having a very low gas permeability must be used.
However, in such a container, there may be a problem in the transparency of the container wall, and in the case of a gas-impermeable resin material, the freeze-dried drug may be adversely affected. Second, the thermal conductivity of the plastic material itself is poor, and if the thickness of the container wall is increased, the freezing treatment during freeze-drying takes time, which hinders mass production. Therefore, the present invention enables quick and easy freeze-drying in a plastic container that is safe to handle and easy to discard by incineration, and that preserves the dried product for a long period of time without adverse effects such as deterioration. It is an object of the present invention to provide a freeze-dried product that can be used and a method for producing the same.

[0004]

The present invention relates to a freeze-dried product obtained by filling a plastic container with a liquid and then freeze-drying the liquid, wherein at least the bottom of the plastic container is formed to be thin, The above object has been achieved by providing a freeze-dried product using a plastic container, wherein the thin wall of the container is hermetically covered with a gas permeation preventing member.

[0005] The plastic container is a thermoplastic resin,
Polyolefin resin, polystyrene resin, polyvinyl chloride resin, polyvinylidene chloride, polyvinyl alcohol resin, polyacrylonitrile resin, polyacrylic acid resin, gen resin, polyamide resin, polyester resin, polycarbonate, polyacetal, fluorine Resin, polyurethane resin and the like. Examples of the polyolefin resin include polyethylene, polypropylene, 4-methylpentene-1, polybutene-1, and linear low-density polyethylene. Examples of the polyvinyl alcohol-based resin include an ethylene-vinyl alcohol copolymer, an ethylene-vinyl acetate copolymer, and a syndiotactic polyvinyl alcohol. Examples of the gen-based resin include polybutadiene-based, polyisoprene-based, and cyclized-gen-based resins. It is desirable that the plastic container has transparency so that the contents can be confirmed and does not adversely affect the contents. Examples of such a plastic container include polyolefin-based resins such as linear low-density polyethylene, high-density polyethylene, polypropylene, and ethylene-vinyl acetate copolymer. Further, a copolymer of polyethylene and a cyclic olefin is also preferable in terms of heat resistance, transparency and the like. Further, the plastic container may have a multi-layer structure in order to have the functionality of the container wall. For example, the inner layer may be made of an olefin-based resin, the intermediate layer may be made of a polyvinyl alcohol-based resin, and the outer layer may be made of polyethylene terephthalate or an olefin-based resin, as long as the transparency is sufficiently maintained without affecting the contents. . In such a multi-layered resin container, the contents of the container are not affected, and the container walls have water vapor resistance, oxygen resistance, carbon dioxide resistance, etc. It can also enhance the character. Plastic containers include extruded tubes,
Molded from a sheet or the like, molded by injection molding, or molded by blow molding. In particular, an extruded tube or a blow-molded plastic container is preferable because a thin wall described later can be easily formed.

In the present invention, the bottom of the plastic container may be formed to be at least thin, and the thin wall may be formed to a part of the bottom or to the bottom and side portions. The thin wall is
Thickness in the range of 10-3000 μm, especially 50-2000
It is desirable that the thickness is formed in the range of μm. If the thickness of the thin wall is less than the above range, the thin wall may be damaged during the liquid material filling step or the freeze-drying step. If the thickness of the thin wall exceeds the above range, the thermal conductivity from the mounting surface becomes poor during the freezing step of the liquid medicine, which hinders mass production and the like. The thin wall can be formed during blow molding or injection molding of the container. However, in the present invention, it is desirable that the thin wall is formed by opening the bottom of the plastic container and fixing a resin sheet or film to the opening. For example, an extruded tube may be used as a body, an opening at one end may be used as a bottom, and a resin sheet or a film may be heat-sealed and adhered to the periphery of the opening at the bottom at the bottom. Further, the bottom of the blow molded product or the injection molded product may be cut once, and a resin sheet or a film may be attached to the cut opening to form. In such a method of forming a thin wall, the thin wall can be provided to a desired thickness regardless of the molding conditions of the body wall of the container.

In the present invention, the entire thin wall is hermetically covered with a gas permeation preventing member. The gas permeation preventing member can sufficiently prevent the permeation of gas that affects the contents by passing through the thin wall during the storage period. Accordingly, the gas permeable preventing member is made of a resin material, an organic material or an inorganic material having a large thickness so as to minimize the permeation amount of the gas during the storage period, and particularly, a gas non-permeable metal such as aluminum or stainless steel. The material is a gas-impermeable organic material such as thick polyvinyl alcohol or vinylidene chloride. The gas that alters the contents is mainly oxygen, water vapor, or the like. For this reason, the oxygen permeation amount (20 ° C.) of the gas permeation preventing member is 0 to
^{1.7cc / m 2 * 24hrs * atm} , in particular, 0~0.1cc / m ² * 24hrs
* atm is desirable. The case where the oxygen permeation amount is 0 is a case where a non-permeable metal foil such as aluminum is used. If the amount of oxygen permeation exceeds the above range, there is a possibility that alteration of the contents cannot be sufficiently prevented.

In the present invention, the gas permeation preventing member is desirably made of an elastic material.
There are thermoplastic elastomers and the like. Silicon rubber or the like is desirable as the rubber material. Thermoplastic elastomers include polystyrene-based thermoplastic elastomers, polyolefin-based thermoplastic elastomers, polyurethane-based thermoplastic elastomers, polyester-based thermoplastic elastomers, polyamide-based thermoplastic elastomers, low-crystalline 1,2-polybutadiene elastomer, and chlorinated polymer-based thermoplastics. Elastomers, fluorinated thermoplastic elastomers, ion-crosslinked thermoplastic elastomers, and the like. When the gas permeation preventing member is made of an elastic material, it can effectively act to prevent damage such as impact, and can be sufficiently adhered to the container wall to sufficiently maintain the confidentiality of the thin wall. In the present invention, it is desirable to insert a deoxidizer between the thin wall and the gas permeation preventing member. As oxygen absorbers, ascorbic acid,
Organic compounds mainly composed of catechol-based compounds, and powdery ones composed of a metal such as iron and a metal halide are available. Specifically, it is commercially available from the trade name “Ageless” (Mitsubishi Gas Chemical Co., Ltd.) or other manufacturers. Examples of the oxygen scavenger include those that only absorb oxygen and those that absorb oxygen to generate carbon dioxide gas.
The oxygen scavenger has the function of removing oxygen in the container through the thin wall and the function of removing a small amount of oxygen permeating from the gas permeation prevention member. Can be prevented. The contents are mainly antibiotics and the like, but in the present invention, it is not necessary to limit to antibiotics as long as they are freeze-dried.

Next, in the method for producing a freeze-dried product using the plastic container according to the present invention, first, a plastic container having the above-mentioned thin wall is provided. Various methods can be adopted for forming the thin wall of the container. For example, at the time of blow molding or injection molding of the container body, the bottom or the portion including the bottom and the side may be formed thin.
Alternatively, a container body having no bottom portion may be formed in advance, and a resin sheet or film of substantially the same quality as the container may be hermetically attached to the bottom portion. In such a case, an extruded tube, a blow-molded product or an injection-molded product with a bottom cut out can be used as the bottomless container body. In particular, a container using an extruded tube is extremely preferable in a mass production process. Next, a predetermined amount of the liquid agent to be freeze-dried is filled in the container. It is desirable to fill the liquid preparation under aseptic conditions with a sterilization filter or the like. A rubber stopper is inserted into the opening of the container containing the liquid agent in a half-stopped state. Such a container is placed so as to be almost in close contact with the mounting surface of the freeze dryer or the freezer, and the liquid in the container is frozen. When the liquid is frozen, the bottom of the container is a thin wall, so that the liquid is efficiently cooled from the mounting surface, and the liquid can be quickly frozen as in the case of the glass vial. Therefore, the freezing step does not hinder the mass production of freeze-dried products. In the freezing step according to the present invention, it is desirable that the mounting surface be once heated after the freezing treatment of the liquid agent. In many cases, the mounting surface and the thin wall of the container are bound after freezing, and once heated, the container can be removed from the mounting surface without damaging the thin wall. Next, before or after drying the liquid, the thin wall of the container is covered with a gas permeation preventing member. When the gas permeation preventing member covers the thin wall in an airtight manner, if the preventing member is a resin, the gas permeation preventing member can be hermetically fixed to the container by heat welding or an adhesive. If the prevention member is an elastic material, it can be airtightly adhered to the container wall. The drying step is performed in an aseptic and dust-free state by increasing the degree of vacuum, and when the moisture has completely sublimated, the rubber stopper is completely capped. After stoppering, wrap it with an aluminum cap or the like and freeze-dry it. The freeze-dried product thus produced can be mass-produced and does not deteriorate because external oxygen or the like does not enter the container.

[0010]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Preferred embodiments of a freeze-dried product using a plastic container according to the present invention will be described below in detail with reference to the accompanying drawings. FIG. 1 is a sectional view of a first embodiment of a freeze-dried product using a plastic container according to the present invention. FIG.
(A) And (B) is sectional drawing of the plastic container in the manufacturing process of the freeze-dried product of 1st Example. FIG. 3 is a sectional view of a freeze-dried product using a plastic container according to a second embodiment of the present invention. FIGS. 4A to 4F are cross-sectional views of a plastic container in a freeze-dried product manufacturing process according to the second embodiment.

As shown in FIGS. 1 and 2, a freeze-dried product 1 using a plastic container of this embodiment is a freeze-dried product obtained by filling a plastic container 2 with a liquid agent 3 and then freeze-drying the liquid agent 3. is there. The bottom 2A and a part of the side 2B of the plastic container 2 are formed to be thin, and the thin walls 2A and 2B of the container 2 are hermetically covered with a gas permeation preventing member 4. The thin walls 2A and 2B are formed thin in the range of 10 to 3000 μm.

The lyophilized product 1 of this embodiment will be described in more detail. The plastic container 2 used for the lyophilized product 1
Is an injection molded product of polypropylene. Thin walls 2A and 2B are formed at a part of the bottom and side portions of the plastic container 2, and the thickness of the thin walls 2A and 2B is 1000 μm, and the other walls are formed at 4000 μm. An opening 5 is formed in the container 2, and the opening 5 is sealed with a rubber stopper 6. The lyophilized product 7 is contained in the container 2, and the lyophilized product 7 is an antibiotic that undergoes deterioration due to the presence of oxygen or the like. Further, the thin walls 2A and 2B of the container 2 are covered with a gas permeation prevention member 4, and the gas permeation prevention member 4 is made of a molded article of polypropylene. Although not shown in FIG. 1, the outer surface of the gas permeation preventing member 4 is provided with aluminum vapor deposition, and the gas permeation preventing member 4 has gas barrier properties. The gas permeation preventing member 4 is almost closely attached to the thin walls 2A and 2B, and is fixed to the side wall of the container 2 by thermal welding. For this reason,
The thin walls 2A, 2B are airtightly covered by a gas permeation preventing member 4.

Next, a method for producing a freeze-dried product according to the first embodiment will be described. First, as shown in FIG. 2A, the plastic container 2 is molded. Thin wall 2 for molding
A and 2B are also formed at the same time. Next, the solution 3 to be freeze-dried
From the opening 5 of the plastic container 2. The liquid agent 3 is aseptically filled through a sterilization filter. After the filling of the liquid agent 3, a rubber stopper 6 is fitted into the opening 5 of the plastic container 2 in a half-stopped state, and is placed on a placing plate 8 in a freezer as shown in FIG. 2 (B). Cool the mounting plate 8 and the inside of the freezer to
Freeze. After freezing, once the mounting plate 8 is heated, the plastic container 2 is removed from the mounting plate 8, and the thin wall 2A,
2B is covered with a gas permeation prevention member 4. The plastic container 2 is lyophilized in a vacuum drying chamber or a freezer in a vacuum state. After drying, an inert gas such as nitrogen gas is introduced into a drying chamber or a freezer.
Is completely plugged into the opening 5 to seal the opening 5. Next, the gas permeation prevention member 4 is thermally welded to the side wall of the container 2, and the gas permeation prevention member 4 covers the thin walls 2 </ b> A and 2 </ b> B in an air-tight manner to obtain the freeze-dried product 1. As a comparative example, one in which the gas permeation preventing member was not provided on the thin walls 2A and 2B was manufactured. The freeze-dried product 1 and the comparative sample were placed in a desiccator, and their changes with time were examined. The freeze-dried product in the comparative sample turned brown in one month, but the freeze-dried product 7 of the freeze-dried product 1 did not change color. Was.

Next, a freeze-dried product using the plastic container of the second embodiment will be described in detail. As shown in FIGS. 3 and 4, the freeze-dried product 9 is
After filling 1, the solution 11 is freeze-dried. In the freeze-dried product 9, the bottom of the plastic container 10 is formed to be thin, and the thin wall 12 of the container 10 is hermetically covered with a gas permeation preventing member 13. 1 thin wall 12
It is formed thin in the range of 0 to 3000 μm. The thin wall 12 is formed by opening the bottom of the plastic container 10 and fixing a resin sheet to the opening 14. Thin wall 1
An oxygen scavenger 16 is inserted between 2 and the gas permeation preventing member 13. The gas permeation preventing member 13 is formed of an elastic material, that is, a rubber material.

The freeze-dried product 9 of this embodiment will be described in more detail. The plastic container 1 used for the freeze-dried product 9
0 is an extruded tube of linear low density polyethylene,
An opening 14 at one end of the molded tube is formed with a resin sheet fixed thereto and formed as a bottom of the container 10. The thin wall 12 made of a resin sheet is made of a low-density polyethylene sheet having a thickness of 250 μm, and the molded tube has a thickness of 4000 μm and a polyvinyl alcohol layer 17 having a thickness of 30 μm as an intermediate layer.
The opening 18 at the other end of the molded tube is sealed with a rubber stopper 19 and furthermore, an aluminum cap 20 is fastened. A lyophilized product 15 is accommodated in the container 10, and the lyophilized product 15 is an antibiotic that undergoes deterioration due to the presence of oxygen or the like. Container 2
The thin wall 12 is airtightly covered with a gas permeation prevention member 13,
The gas permeation preventing member 13 is made of a molded product of silicon rubber. An oxygen absorber 16 is disposed between the gas permeation preventing member 13 and the thin wall 12. The oxygen transmission rate (20 ° C.) of the silicone rubber is 0 to 0.1 cc / m ² * 24 hrs * atm.

Next, a method for producing a freeze-dried product according to the second embodiment will be described. First, as shown in FIG. 4A, an extruded tube as a main body of the plastic container 10 is formed by co-extrusion of linear low-density polyethylene and polyvinyl alcohol, and cut into a predetermined length. As shown in FIG. 4B, a ring-shaped flange 21 is attached to the opening 18 at the other end of the extruded tube. As shown in FIG. 4 (C), a plastic sheet 10 as a thin wall 12 is heat-welded to an opening 14 at one end of the extruded tube to produce a plastic container 10. FIG.
As shown in (D), the liquid 11 to be freeze-dried is filled through the opening 18 of the plastic container 10. The solution 11 is aseptically filled through a sterilization filter. After filling the liquid agent 11,
A rubber stopper 19 is fitted into the opening 18 of the plastic container 10 in a half-stopped state, and is placed on a placement plate 22 in a freezer as shown in FIG. The liquid plate 11 is frozen by cooling the mounting plate 22 and the inside of the freezer. After freezing, the mounting plate 22 is once heated to remove the plastic container 10 from the mounting plate 22, and the gas permeation preventing member 13 is liquid-tightly covered on the thin wall 12 with the oxygen absorber 16 interposed therebetween. As shown in FIG. 4 (F), the plastic container 10 is lyophilized in a vacuum drying chamber or a freezer in a vacuum state. After drying, an inert gas such as nitrogen gas is introduced into a drying chamber or a freezer. After the introduction, a rubber stopper 19 is completely plugged into the opening 18 to open the opening 18.
Seal. Next, the aluminum cap 20 is wound around the rubber stopper 19. This is referred to as a freeze-dried product 9. In such a freeze-dried product 9, molding of the plastic container 10 and formation of the thin wall 12 are extremely easy, and have a structure suitable for mass production. Further, the oxygen absorber 16 is used for the thin wall 1.
2, the oxygen scavenger 16 can remove oxygen in the container 10 through the thin wall 12 and can remove a small amount of oxygen permeating from the gas permeation preventing member 13. it can.

[0017]

As described above, in the freeze-dried product using the plastic container according to the present invention and the method for producing the same, at least the bottom of the plastic container is formed thin, and the thin wall of the container is formed thin. Since it is air-tightly covered with a gas permeation prevention member, it can be freeze-dried quickly and easily in a plastic container that is safe to handle and can be easily incinerated and disposed of, and does not adversely affect the quality of the dried product. Can be stored for a long time.

[Brief description of the drawings]

FIG. 1 is a sectional view of a first embodiment of a freeze-dried product using a plastic container according to the present invention.

FIGS. 2A and 2B are cross-sectional views of a plastic container in a freeze-dried product manufacturing process of the first embodiment.

FIG. 3 is a sectional view of a freeze-dried product using a plastic container according to a second embodiment of the present invention.

FIGS. 4A to 4F are cross-sectional views of a plastic container in a freeze-dried product manufacturing process according to a second embodiment.

[Explanation of symbols]

 1, 9 freeze-dried product 2 plastic container 2A, 2B thin wall 3 liquid material 4 gas permeation prevention member 5 opening 6 rubber stopper

Claims (8)

[Claims] 1. After filling a plastic container with a liquid agent,
A freeze-dried product obtained by freeze-drying the liquid agent, wherein at least the bottom of the plastic container is formed to be thin, and the thin wall of the container is air-tightly covered with a gas permeation preventing member. A freeze-dried product using a characteristic plastic container. 2. A freeze-dried product using a plastic container according to claim 1, wherein said thin wall is formed to be thin in a range of 10 to 3000 μm. 3. The thin wall is formed by opening a bottom portion of the plastic container and fixing a resin sheet or film to the opening.
A freeze-dried product using the plastic container described. 4. An oxygen absorber is inserted between the thin wall and the gas permeation preventing member.
4. A freeze-dried product using the plastic container according to any of 3. 5. A freeze-dried product using a plastic container according to claim 1, wherein the gas permeation preventing member is formed of an elastic material. 6. The freezing method using a plastic container according to claim 1, wherein the gas permeation preventing member is formed of a gas impermeable inorganic material or a gas impervious organic material. Dried goods. 7. The method for producing a lyophilized product according to claim 1, wherein the container is placed on a lyophilizer or a mounting surface of a freezer to freeze-treat the liquid, and then, A method for producing a freeze-dried product using a plastic container, wherein the thin wall of the container is covered with a gas permeation preventing member before or after drying. 8. The method for producing a freeze-dried product using a plastic container according to claim 7, wherein the mounting surface is once heated after the freezing treatment of the liquid agent.