JPH05237162A - Liquid chemical container housing body - Google Patents

Abstract

PURPOSE:To prevent the deterioration of properties of a liquid chemical over a long period even at the time of high-pressure steam sterilization and sterilization by sealing a liquid chemical container in which oxygen is substd. with an inert gas together with a deoxidizing agent into a packaging container having gaseous oxygen impermeability and heat resistance. CONSTITUTION:This liquid chemical container 12 is formed of a soft plastic material having heat resistance, for which straight chain low-density polyethylene having low steam permeability is suitable. The inside of the liquid chemical container 12 is substd. with nitrogen and the gaseous nitrogen is injected simultaneously with the liquid chemical 15 at the time of injecting the liquid chemical from a discharge port 16 into the container. The discharge port 16 is hermetically sealed by a plastic material after the injection and a rubber plug is mounted thereto. Further, the discharge port is sealed by the plastic film. The liquid chemical container 12 contg. the liquid chemical 15 is then put together with the deoxidizing agent 14 into the packaging container 13 and the deoxidizing agent 14 is coated with a structural body 17 having holes communicating from one surface with the other surface. At least 50% moisture is imparted to the gas in the packaging container 13. The liquid chemical container housing body 11 is then subjected to the high-pressure steam sterilization in the steam where oxygen does not exist in an autoclave.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a drug solution container housing. In particular, it relates to high-pressure steam sterilization and a container for a liquid medicine container that does not deteriorate the liquid medicine for a long period of time.

[0002]

2. Description of the Related Art In recent years, in medical treatment such as infusion, a closed system has been used in order to prevent the content liquid from coming into contact with the outside world. The medical solution container for medical use used in this closed system needs to discharge the content liquid due to gravity, the structure of the container, and the flexibility of the material of the container. Further, this type of medical liquid container is required to have heat resistance to withstand high-pressure steam sterilization in order to sterilize the content liquid. Further, it is preferably made of a transparent material so that the content liquid can be monitored from the outside. Conventional containers containing chemicals have been glass bottles and glass ampoules, but plastic containers containing chemicals have been put on the market so that they can be used in closed systems.

[0003]

A plastic container containing a chemical solution of this kind is usually subjected to high-pressure steam sterilization to sterilize the content solution. At room temperature, even plastic materials with low gas permeability, such as polyvinyl chloride, will have high gas permeability during high-pressure steam sterilization, and oxygen existing in the atmosphere will enter the container through the container wall formed of the plastic material. It will be easier. Also, even at room temperature, plastic containers have higher gas permeability than glass bottles and glass ampoules, so plastic containers are packed with a packaging material with a high gas barrier property, but even if they are stored for a long period of time, the atmosphere will change. Oxygen existing inside penetrates the container wall gradually and enters the container. The drug solution in the container contains high-concentration amino acid infusion containing tryptophan, fat emulsion for infusion, and infusions containing antibiotics that are easily oxidized or hydrolyzed by the presence of oxygen. In many cases, there is a risk of deterioration and discoloration.

[0004]

[MEANS FOR SOLVING THE PROBLEMS] In a container having at least one discharge port formed of a flexible plastic material having heat resistance, a chemical solution containing a component which is easily deteriorated by oxygen is oxygen in the container and in the chemical solution. The chemical solution container filled with the inert gas replaced with the oxygen absorber,
It is enclosed in a packaging container having high oxygen gas impermeability, heat resistance and transparency so that there is a space around at least the oxygen scavenger, and is constituted by the outside of the liquid medicine container and the inside of the packaging container. The space itself forms a barrier layer in a substantially oxygen-free state that prevents oxygen permeation into the liquid medicine container, and
The above-mentioned problems have been solved by providing a drug solution container container for highly preventing deterioration of a drug solution, which is characterized in that at least the drug solution container is subjected to high-pressure steam sterilization.

[0005]

The inventors of the present invention have conducted various studies to develop a drug solution container container in which the drug solution does not deteriorate during and after high-pressure steam sterilization, and as a result, a flexible plastic material having heat resistance was used. Both the container containing the chemical solution and the oxygen scavenger formed in at least one or more outlets are provided with heat resistance and high oxygen gas impermeability so that at least a space exists around the oxygen absorber. By enclosing it in the packaging container that it has, the chemical solution does not deteriorate even if the packaging material becomes easily permeable to oxygen during high-pressure steam sterilization, and the chemical solution deteriorates for a long period after sterilization. The inventors have found that there is nothing and have completed the present invention.

Since the drug solution container of the present invention is subjected to high-pressure steam sterilization, it must be formed of a flexible plastic material having heat resistance capable of withstanding the sterilization temperature. Further, it is preferable that it has excellent strength, water vapor permeation resistance and transparency. Plastic materials satisfying such conditions include soft polyvinyl chloride, crosslinked ethylene-vinyl acetate copolymer, linear low density polyethylene and the like.

The drug solution containing a component which is easily deteriorated by oxygen contained in the above-mentioned plastic container includes a high concentration amino acid infusion solution and a fat emulsion containing at least one high calorie solution component (transparental parenteral nutrition component), especially tryptophan,
Also included are infusions containing antibiotics that are easily oxidized or hydrolyzed by the presence of oxygen.

The chemical solution is dispensed into the plastic container. At this time, it is preferable to replace the inside of the container and the chemical liquid with an inert gas so that oxygen is not substantially present in the container and the chemical liquid, and the container is sealed. For example, after injecting a chemical solution into a plastic container, a method of bubbling an inert gas into the chemical solution so that oxygen does not exist in the container and the chemical solution, or a chemical solution previously replaced with an inert gas may be used. May be injected together with an inert gas so that oxygen does not exist in the container and in the chemical solution. Although there are various inert gases used, nitrogen gas is preferable from the viewpoint of cost.

Next, the chemical liquid container is placed together with the oxygen scavenger so that a space exists at least around the oxygen scavenger.
Wrap with a packaging material that has heat resistance and high oxygen gas impermeable properties (ie, enclose in a packaging container). If the oxygen scavenger is packed with a packaging material so that there is no space around it, the oxygen scavenging effect of the oxygen scavenger deteriorates, and the chemical liquid in the chemical liquid container is altered by oxygen during high-pressure steam sterilization or storage. Easier to do. The method of allowing a space to exist around the oxygen scavenger is, when the chemical solution container and the oxygen scavenger are put in a packaging container, a method of introducing air or an inert gas, or communicating the oxygen scavenger from one surface to the other surface. A method of covering with a structure having holes, a method of placing an oxygen absorber and a chemical solution container on a plate having irregularities and placing it in a packaging container, a method of providing a convex portion on the packaging container, a tray part and a sheet-like lid There is a method of using a packaging container composed of.

Further, the amount of the oxygen scavenger used is required to be an amount capable of maintaining an oxygen concentration in the chemical liquid during high-pressure steam sterilization and during long-term storage, which does not cause deterioration due to oxidation of the chemical liquid by oxygen or the like. is there. For example, in the case of a liquid medicine container containing 400 ml of a high-concentration amino acid transfusion, an oxygen absorption amount of 10 ml or more is required, and it is preferable to use a deoxidizer having an oxygen absorption amount of 100 ml or more.

As the oxygen scavenger, powdery ones made of a metal such as iron and a metal halide, and organic ones mainly containing ascorbic acid or catechol are known. These oxygen scavengers are commercially available from Mitsubishi Gas Chemical Co., Inc. [trade name: Ageless] and several other manufacturers. Among these oxygen absorbers, there are one that only absorbs oxygen and one that releases carbon dioxide at the same time as oxygen is absorbed. When a packaging container composed of a tray portion and a sheet-like lid is used, it is preferable to use a deoxidizing agent that releases carbon dioxide at the same time as absorbing oxygen. In other words, if oxygen is removed from the packaging container with an oxygen scavenger, the pressure inside the packaging container will drop, which may cause problems such as pinholes. This is because the internal pressure can be kept constant.

The oxygen scavenger acts to remove oxygen that has permeated the packaging container so that oxygen does not enter the chemical solution container, and oxygen in the chemical solution container and the chemical solution before high-pressure steam sterilization. There is an action of removing the chemicals through the wall of the liquid medicine container.

The material of the packaging container having heat resistance and high oxygen gas impermeability is a three-layer laminate film having an ethylene-vinyl alcohol copolymer film or a polyvinylidene chloride film layer or a laminate film having an aluminum layer. is there. Although the laminated film having the aluminum layer is opaque, its oxygen gas impermeable performance is not affected by humidity. In addition, since the three-layer laminate film made of synthetic resin is transparent, it is possible to easily perform foreign matter inspection and inspection of the degree of alteration of the chemical liquid in the packaging material, but its oxygen gas impermeable performance is affected by humidity. It is easy to receive. Therefore, when high-pressure steam sterilization is performed after the above-mentioned chemical solution container is sealed in a packaging container, the outer layer of this three-layer laminate film is preferably laminated with a resin having heat resistance and relatively high water vapor permeability, such as polyamide resin. That is, during high-pressure steam sterilization to be described later, since the layer of the ethylene-vinyl alcohol copolymer film or polyvinylidene chloride film of the intermediate layer absorbs moisture easily and oxygen gas easily permeates, a resin having relatively high water vapor permeability is used for the outer layer. This is because moisture absorbed can be easily evaporated in a short time, and as a result, the high oxygen gas impermeable property can be restored in a short time. A resin having low water vapor permeability is preferably laminated on the inner layer of the three-layer laminate film. That is, even if the liquid medicine in the liquid medicine container permeates the container wall, if the inner layer of this sheet is a resin having low water vapor permeability, the ethylene-vinyl alcohol copolymer film or polyvinylidene chloride film of the intermediate layer is almost the same. This is because this packaging container can maintain high oxygen gas impermeable property without absorbing moisture.
It is preferable to laminate an unstretched polypropylene film or an unstretched polyethylene film on this inner layer,
Good thermal weldability.

Further, after high-pressure steam sterilization, it is preferable to actively evaporate the moisture absorbed by the above-mentioned three-layer laminate film in a dryer such as an oven. Furthermore, it is more preferable to perform the above-mentioned drying in an inert gas atmosphere. That is, since the oxygen gas impermeability of the three-layer laminate film is restored in a short time, it is possible to more reliably prevent the chemical liquid from being deteriorated due to oxidation with oxygen or the like for a longer time.

Further, the above-mentioned three-layer laminated film is used on one side of a packaging container, or in the case of a packaging container composed of a tray part and a sheet-like lid, the three-layer laminated film is formed on the tray part or the sheet-like lid. On the other hand, a laminated film having an aluminum layer may be used in place of the above-mentioned ethylene-vinyl alcohol copolymer film on the other surface or the rest of the tray part or the sheet-like lid. In this way, since either one side of the packaging container or the tray portion or the sheet-like lid body becomes transparent, it is possible to easily perform the foreign substance inspection and the alteration degree inspection of the chemical liquid in the packaging container, Moreover, the influence of humidity on the oxygen gas impermeable performance can be reduced.

Further, when the above-mentioned transparent three-layer laminate film is used, some chemicals are likely to be deteriorated by ultraviolet rays. Therefore, at least one layer of the three-layer laminate film absorbs ultraviolet rays of benzophenone type or phenyl salicylate type. It is preferable to add an agent or to color it in order to make it difficult to transmit ultraviolet rays.

Next, the container for the liquid medicine container packaged with the packaging material as described above is subjected to high-pressure steam sterilization. As a sterilization method,
An autoclave, a tower autoclave, a funnel mat, etc. are used. Even if oxygen gas is present in the atmosphere during high-pressure steam sterilization and the packaging material is in a state where oxygen gas easily permeates, the oxygen that has permeated the packaging material is removed by the oxygen scavenger. The chemical solution of is not altered by oxygen. Further, in the case of an autoclave, it is more preferable to maintain the pressure during high-pressure steam sterilization by introducing an inert gas into the atmosphere. In the case of a tower autoclave and a funnel mat, it is more preferable to replace water with an inert gas so that oxygen is substantially absent. The inert gas used is preferably nitrogen gas.

In the drug solution container housing thus manufactured, the drug solution in the drug solution container is substantially anoxic and sterilized, and the space between the drug solution container and the packaging container is substantially Since it is an oxygen-free and sterilized barrier layer, even if it is stored for a long period of time, the deterioration due to the oxidation of the internal chemical liquid by oxygen or the like hardly occurs.

In addition, it is possible to manufacture a liquid medicine container housing for preventing the deterioration of the liquid medicine by oxygen by another method. First, the chemical solution container is manufactured as described above. Next, this chemical solution container is subjected to high-pressure steam sterilization. As a sterilization method, an autoclave, a tower autoclave, a funnel mat, or the like is used as described above. In the case of an autoclave, the pressure during autoclave sterilization and cooling after sterilization is maintained by introducing an inert gas into the atmosphere. For tower autoclaves and funnel mats, replace water with an inert gas to prevent oxygen from entering the chemical solution container.
The inert gas used is preferably nitrogen gas.

After sterilization, the chemical solution container is packaged together with the oxygen scavenger in a packaging material having a high oxygen gas impermeable property so that a space exists at least around the oxygen scavenger. If the oxygen scavenger is packed with packaging material so that there is no space around it, the oxygen scavenging effect of the oxygen scavenger deteriorates, as described above, and the chemical solution in the chemical solution container is oxidized by oxygen during storage after sterilization. Deterioration due to, for example, is likely to occur. Further, as a method for allowing a space to exist around the oxygen absorber, as described above, when the chemical solution container and the oxygen absorber are put into the packaging material, a method of simultaneously introducing air or an inert gas, or an oxygen absorber is used. A method of covering with a structure having holes that communicate from one side to the other side, a method of placing an oxygen absorber and a chemical solution container on a plate with unevenness and placing it in the packaging material, a method of providing a convex portion on the packaging material, and a tray. There is a method of using a packaging material composed of a portion and a sheet-like lid.

Examples of the packaging material having high impermeability to oxygen gas include a three-layer laminate film having layers of an ethylene-vinyl alcohol copolymer film and a polyvinylidene chloride film, and a laminate film having an aluminum layer. In a three-layer laminated film having transparency, it is preferable to laminate an unstretched polypropylene film or unstretched polyethylene film on the inner layer of the ethylene-vinyl alcohol copolymer film, and the heat fusion property becomes good. Further, it is preferable to laminate a biaxially oriented polypropylene film, a polyethylene film or the like on the outer layer of the ethylene-vinyl alcohol copolymer film in order to reduce the influence of moisture in the external atmosphere. Further, a packaging material having a large thickness such as olefin resin such as polyethylene or polypropylene, polyester, polyurethane, polyamide or the like can be used.
According to this method, a cross-linked ethylene-vinyl acetate copolymer, which easily causes blocking with the packaging material, can be used as the raw material of the plastic container.

The plastic container containing a chemical solution according to the present invention manufactured as described above hardly deteriorates due to oxidation of the internal chemical solution by oxygen even during long-term storage.

[0023]

The present invention will be described in detail with reference to the drawings. As shown in FIG. 1, the liquid medicine container housing 11 of the present invention.
Is composed of a chemical liquid container 12, a packaging container 13, a deoxidizing container 14, and a chemical liquid 15. The chemical liquid container 12 is made of the above-mentioned flexible plastic material, and linear low density polyethylene having low water vapor permeability is particularly suitable. The chemical liquid container 12 is manufactured by various methods. For example, one open end of a tubular sheet obtained by inflation molding of linear low-density polyethylene is heat-welded to provide a suspending port for suspending a drug solution container, and the other open end is provided with a discharge port for heat-insulating. Welding method, two sheets obtained by extrusion molding of linear low-density polyethylene are overlapped, and the peripheral portion is heat-welded, straight-chain low-density polyethylene with a small diameter outlet at the upper end and There is a method in which a blow-molded product having a subsequent container portion is molded, and the blow-molded product is heat-welded in the vicinity of the side peripheral edge portion and / or the lower peripheral edge portion. Of these methods, the method using a blow-molded product is most suitable because the discharge port is not heat-welded and there is no risk of leakage, and this method was used in this example. The above-mentioned chemical solution 15 is injected from the discharge port 16. At this time, the chemical solution 15 to be injected is made substantially oxygen-free, and the chemical solution container 1 is injected immediately before the injection.
The inside of 2 is replaced with nitrogen, and immediately thereafter, a chemical solution and nitrogen gas are simultaneously injected. After the injection, the opening of the discharge port 16 is sealed with a plastic material and a rubber stopper is attached, and in order to keep the outer surface of the rubber stopper aseptic, a plastic film is sealed so that it can be easily peeled off during use.

Next, the drug solution container 12 containing the drug solution 15 is put in the above-mentioned packaging container 13 together with the oxygen scavenger 14. At this time, the oxygen scavenger 14 is covered with a structure 17 having a hole communicating from one surface to the other surface, and is enclosed and enclosed together. Further, the gas in the packaging container 13 was made to have a humidity of at least 50% or more.

Next, the chemical liquid container container 11 is subjected to high-pressure steam sterilization in an atmosphere consisting of steam substantially free of oxygen. This sterilization is performed by, for example, an autoclave. The chemical liquid container housing 11 is housed in a plurality of units in the autoclave. Next, steam is introduced into the autoclave from the boiler for a predetermined time, and the air in the autoclave is discharged. After discharging, steam at a predetermined temperature is introduced into the autoclave and sterilized. An inert gas is appropriately introduced to secure the pressure in the autoclave during sterilization. After sterilization, a predetermined amount of cooling water is introduced into the autoclave to sufficiently cool the drug solution and then taken out.

FIG. 2 shows another container 21 for a liquid medicine container according to the present invention.
Indicates. The chemical liquid container housing 21 is composed of a chemical liquid container 22, a packaging container 23, an oxygen absorber 24, and a chemical liquid 25. The chemical liquid container 22 was manufactured by using a blow molded product as in the case of FIG. Further, the method of injecting the chemical solution 25 from the discharge port 26 was performed in the same manner as in FIG.

Next, the chemical solution container 22 containing the chemical solution 25 is sterilized by high pressure steam in an atmosphere consisting of steam substantially free of oxygen. This sterilization is performed by, for example, an autoclave. A plurality of chemical solution containers are housed in the autoclave. Next, steam is introduced into the autoclave from the boiler for a predetermined time, and the air in the autoclave is discharged. After discharging, steam at a predetermined temperature is introduced into the autoclave and sterilized. An inert gas is appropriately introduced to secure the pressure in the autoclave during sterilization. After sterilization, a predetermined amount of cooling water is introduced into the autoclave to cool the drug solution sufficiently.

After cooling, the chemical solution container is put in the above-mentioned packaging container 23. At this time, nitrogen gas is filled and sealed.

As shown in FIGS. 3 (a) and 3 (b), the oxygen absorber 34 and the chemical solution container are placed on a plate 37 having irregularities and placed in the packaging container 33 to remove the oxygen absorber 34. It is also possible to enhance the oxygen removing effect.

Example 1 A 12% amino acid amino acid infusion solution containing an essential amino acid as a main component was filled in a linear low-density polyethylene bag.
The amino acid infusion and the bag were replaced with nitrogen to make oxygen substantially nonexistent, the outlet was sealed with a linear low-density polyethylene film, a rubber stopper was attached, and polypropylene and polyethylene were blended on top of it. It was sealed with a laminated polyester film.

This bag containing the chemical solution is a three-layer laminate having a biaxially stretched nylon film (thickness 20 μm) as an outer layer, an ethylene-vinyl alcohol copolymer film (thickness 20 μm) as an intermediate layer, and an unstretched polypropylene film as an inner layer. Wrapped in film. At this time, an oxygen absorber (trade name: Ageless Mitsubishi Gas Chemical Co., Ltd.) is enclosed.
The bag was filled with nitrogen gas and sealed so that the oxygen absorber did not come into close contact with the bag containing the liquid medicine and the packaging material. The bag containing the liquid medicine packaged with this packaging material was subjected to high-pressure steam sterilization at 115 ° C. for 40 minutes. A predetermined amount of nitrogen gas was introduced into the autoclave in order to maintain the pressure during sterilization and cooling. After cooling
The bag containing the liquid medicine packaged with the packaging material was taken out. In this way, the desired drug solution container was obtained without breaking the bag.

Example 2 A bag containing a chemical solution was prepared in the same manner as in Example 1. The bag containing the chemical solution was subjected to high-pressure steam sterilization at 115 ° C. for 40 minutes. A predetermined amount of nitrogen gas was introduced into the autoclave in order to maintain the pressure during sterilization and cooling. After cooling, this bag containing the chemical solution was a three-layer laminated film having a biaxially oriented polypropylene film (thickness 20 μm) as an outer layer, a polyvinylidene chloride-coated polyamide film (20 μm) as an intermediate layer, and an unstretched polypropylene film as an inner layer. Packaged. At this time, use a deoxidizer (trade name: Ageless Mitsubishi Gas Chemical Co., Inc.) with a humidity of 60
%, And sealed with air to obtain a desired drug solution bag container.

Comparative Example 1 A chemical solution bag container was obtained in the same manner as in Example 1 except that the oxygen absorber was not used.

Comparative Example 2 A drug solution bag container was obtained in the same manner as in Example 1 except that the oxygen absorber was sealed in such a form that it closely adhered to the drug solution containing bag and the packaging material.

Comparative Example 3 A drug solution bag container was obtained in the same manner as in Example 2 except that the oxygen absorber was sealed in such a form that it closely adhered to the drug solution-containing bag and the packaging material.

Comparative Example 4 As a packaging material, a three-layer structure comprising a biaxially oriented polypropylene film (thickness 20 μm) as an outer layer, an ethylene-vinyl alcohol copolymer film (thickness 20 μm) as an intermediate layer and an unstretched polypropylene film as an inner layer. A drug solution bag container was obtained in the same manner as in Example 1 except that the laminate film was used.

In order to examine the degree of alteration of the drug solution in the drug solution bag housing obtained as described above, visible light (42
The transmittance at 0 nm) was measured, and the results are shown below.

[0038]

[Table 1]

[0039]

【The invention's effect】

(1) It is possible to prevent the deterioration of the drug solution in the container due to oxygen during sterilization and during storage after sterilization, and to store the drug solution in a stable state. (2) Since it is made of plastic, it is light and convenient to carry. (3) The flexible plastic container containing the drug solution can be used in a closed system and can prevent airborne infection. (4) Since the packaging material has transparency, it is easy to inspect foreign matters and observe the storage state.

[Brief description of drawings]

FIG. 1 is a front view showing an embodiment of a chemical liquid container container for preventing the chemical liquid from being deteriorated by oxygen according to the present invention.

FIG. 2 is a front view showing another embodiment of a container for a liquid medicine container for preventing the deterioration of the liquid medicine by oxygen according to the present invention.

FIG. 3 (a) is a front view showing another embodiment of the chemical liquid container container for preventing the chemical liquid from being deteriorated by oxygen according to the present invention,
(B) is a III-III cross-sectional view of the same embodiment.

[Explanation of symbols]

 11,21,31 Chemical liquid container container 12,22,32 Chemical liquid container 13,23,33 Packaging container 14,24,34 Deoxidizer 15,25,35 Chemical liquid 16,26,36 Discharge port 17 Has a communicating hole Structure 37 Plate with unevenness

Claims (6)

[Claims] 1. A chemical liquid containing a component which is easily deteriorated by oxygen in a container having at least one discharge port formed of a flexible plastic material having heat resistance, and oxygen in the container and the chemical liquid is an inert gas. Enclose the chemical solution container filled with the oxygen scavenger together with the oxygen scavenger in a packaging container having high oxygen gas impermeability, heat resistance and transparency so that at least a space exists around the oxygen scavenger. The space itself constituted by the outside of the liquid medicine container and the inside of the packaging container forms a barrier layer in a substantially oxygen-free state that prevents oxygen permeation into the liquid medicine container, and at least the liquid medicine container has a high pressure. A container for a liquid medicine container, which is highly sterilized by steam and highly prevents the deterioration of the liquid medicine. 2. The liquid medicine container container according to claim 1, wherein the oxygen scavenger is covered with a structure having a hole communicating from one surface to the other surface. 3. The oxygen absorber is enclosed in a packaging container so as to be located on a plate having irregularities.
Alternatively, the drug solution container storage body according to item 2. 4. The drug solution container storage body according to claim 1, wherein an inert gas is simultaneously enclosed in the packaging container. 5. The drug solution container storage body according to claim 1, wherein the packaging container is composed of a tray portion and a sheet-like lid body. 6. The drug solution container container according to claim 1, wherein the oxygen scavenger removes oxygen gas and releases carbon dioxide gas.