JP2876959B2 - Manufacturing method of deoxygenated packaging - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for manufacturing a package having deoxidation properties, and more particularly, to a plastic inner package such as an infusion container or the like, which is accommodated in an outer bag provided with an oxygen absorbent-containing resin layer. And a method for producing a package comprising

[0002]

2. Description of the Related Art An infusion container containing a liquid drug as a content is used by directly connecting a tube or the like to the container. Therefore, in order to prevent the container from being contaminated before it is actually used, it is synthesized. It is handled in a state of being filled in an outer sack made of a resin film. Since the infusion container is made of a resin that transmits oxygen from the viewpoint of hygiene and the like, it is necessary that the outer wrapper has a gas barrier property in order to prevent deterioration of the content liquid due to oxygen. However, there is some oxygen in the sealed outer envelope, and even if a barrier outer envelope is used, it is necessary to prevent deterioration of the content liquid due to oxygen permeating with time. For this reason, conventionally, in addition to filling an infusion container under a low oxygen concentration, an oxygen absorbent is put together with an infusion container in an outer envelope bag, and the residual oxygen and further permeated oxygen are captured by the oxygen absorbent. In addition, the amount of oxygen in the outer bag is maintained at a low level to prevent the contents of the infusion container from being deteriorated (Japanese Patent Publication No. 5-33632).

[0003]

However, if the oxygen absorbent filled in the sachet is directly put into such an outer bag, there is a risk that the oxygen absorbent may be inadvertently taken. On the other hand, fixing the oxygen absorbent in the outer envelope so that the oxygen absorbent cannot be easily removed from the outer envelope has a problem that the production process becomes very complicated and productivity is poor. Also,
The use of an oxygen absorber was not economically favorable. Therefore, it has been proposed that the outer bag itself has an oxygen absorbing function (Japanese Utility Model Application No. 5-27076). However, when this oxygen-absorbing outer bag is used, the presence of moisture is necessary for the oxygen absorption reaction. Therefore, it is necessary to perform heat sterilization or retort sterilization after filling the infusion container with a low oxygen concentration in the outer wrapping bag, and there has been a problem that the filling process equipment needs to be changed.

[0004] In addition, due to the nature of the content liquid to be filled in the infusion container and problems in the manufacturing process, it may not be preferable to perform heat sterilization or retort sterilization after filling the infusion container in the outer wrapping bag. In the method, after filling the infusion container into the outer envelope, it is necessary to supply water into the outer envelope to activate the oxygen absorption reaction.

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide an outer bag for a plastic container that effectively captures oxygen permeating from the outside and remains in the outer bag without filling the outer container with a plastic container and then performing retort sterilization or the like. Another object of the present invention is to provide a method for manufacturing a deoxygenated package excellent in preservation of contents by effectively trapping oxygen generated. Another object of the present invention is to provide a suitable method for allowing an appropriate amount of moisture to exist in an outer bag filled with a plastic container.

[0006]

According to the present invention, a plastic inner package filled with contents and sealed therein is filled in a heat-sealable outer package provided with an oxygen absorbent compounding layer, and the outer package and the inner package are filled. The present invention provides a method for producing a deoxygenated package characterized in that a sufficient amount of water for activating an oxygen absorbent coexists between the two, and then the outer packaging bag is sealed by heat sealing.

In the present invention, the space between the outer envelope and the inner envelope is replaced or filled with humidified nitrogen, water is supplied in the form of droplets or sprays, or the label of the inner envelope is labeled. It is preferable that moisture is allowed to coexist between the outer envelope and the inner envelope by absorbing moisture in advance.

[0008]

According to the present invention, an oxygen absorbent is provided between a heat-sealing outer wrapping bag provided with an oxygen-absorbing agent-containing resin layer and a plastic inner wrapper filled and sealed with the contents filled in the outer wrapping bag. By coexisting a sufficient amount of water for activation, it is possible to effectively capture the residual oxygen in the outer envelope, and to provide a deoxygenated package excellent in the storage stability of the content liquid. It is.

As described above, the presence of moisture is indispensable for the oxygen absorbent to capture oxygen. In a conventional outer envelope, retort sterilization or the like is performed after filling the plastic inner envelope. Although the water generated at that time is used, if retort sterilization or the like must be performed before filling the plastic inner package, it is necessary to supply the moisture together with the inner package into the outer package. In the present invention, by providing the oxygen-absorbing agent-containing resin layer as one layer of the laminate constituting the outer wrapping bag, erroneous use of the oxygen absorbing agent is prevented, and troublesome work of putting the inside of the outer wrapping bag is unnecessary. In addition, when moisture coexists directly in the outer bag,
Leakage of the oxygen absorbent is effectively prevented.

FIG. 1 is a graph showing the change over time of the oxygen concentration in the outer wrapping bag in which water is present in the outer wrapping bag used in the present invention by changing the supply amount. As can be seen from the graph, in the case where no water was added, the oxygen concentration increased gradually but without decreasing, whereas in the case where water was present, the oxygen concentration was increased from the time of filling until the 15th. The concentration is gradually reduced to prevent the contents from being altered by oxygen. Especially 1.5g / l and 3g of water
It is understood that the oxygen concentration was further reduced even after 30 days, and that the residual oxygen in the outer envelope was captured over a long period of time. The degree of oxygen reduction naturally depends on the container configuration, material configuration, and container size.

[0011]

A preferred embodiment of the present invention is a heat-sealable outer bag provided with an oxygen absorbent, as described above. Specifically, it suppresses the permeation of oxygen from the outside. For this purpose, the outer layer needs to have gas barrier properties, and the inner layer must have moisture resistance because it supplies moisture into the outer wrapper. Preferably, the first laminated sheet 2 provided with the gas barrier layer 8, the oxygen absorbent-containing resin intermediate layer 7 and the heat sealable resin inner layer 6a proposed by the present inventors as shown in FIG. Pinhole resin layer 1
2. Gas barrier layer 11 and heat sealing resin inner layer 6
It is particularly preferable to use an outer wrapping bag in which the transparent second laminated sheet 3 provided with b is overlapped so that the heat-sealable resin layers face each other and the edges are heat-sealed.
Since the outer bag has transparency, the state of the contents can be grasped without opening the outer bag, and since the outer bag is excellent in pinhole resistance, the outer bag is also sealed. It is well maintained. FIG. 3 shows an infusion container 13 (label 14 absorbed by moisture) in outer bag 1 by the method of the present invention.
Shows an example of a state in which is attached.

[0012] As the oxygen absorbent compounded in the outer bag,
All oxygen absorbers conventionally used for this type of application can be used, but generally, those which are reducing and are substantially insoluble in water are preferable, and suitable examples thereof include metal powder having a reducing property, for example, Reducing iron, reducing zinc, reducing tin powder; lower metal oxides such as ferrous oxide and ferric oxide;
The main component is a reducing metal compound, for example, one or a combination of iron carbide, silicon iron, iron carbonyl, ferrous hydroxide and the like. These are, if necessary, hydroxides, carbonates, sulfites, thiosulfates, tertiary phosphates, organic acid salts, halides of alkali metals and alkaline earth metals, as well as activated carbon, activated alumina and activated clay. It can be used in combination with such auxiliaries. Alternatively, a polymer compound having a polyhydric phenol in the skeleton, such as a phenol-aldehyde resin containing a polyhydric phenol, may be used. These oxygen absorbents generally have an average particle size of 50 μm or less, preferably 30 μm or less.
The oxygen absorbent is preferably added to the following resin at a ratio of 1 to 100% by weight, particularly 10 to 70% by weight.

As the resin in which the oxygen absorbent is blended, various known resins capable of forming a film can be used. Among them, a resin in which the layer containing the oxygen absorbent can effectively absorb moisture is used. A resin having water absorption per se, for example, an ethylene-vinyl acetate copolymer having an ethylene content of 20 to 60 mol%, particularly 25 to 50 mol%, is converted into a saponification degree of 96 mol% or more, particularly 99 mol% or more. An ethylene vinyl alcohol copolymer, which is a saponified copolymer obtained by saponifying so that The saponified ethylene vinyl alcohol copolymer should have a molecular weight sufficient to form a film, and is generally 0.01 dl / measured at 30 ° C. in a mixed solvent having a weight ratio of phenol: water of 85:15. It preferably has a viscosity of at least g, especially at least 0.05 dl / g.

Further, resins which do not themselves absorb water, such as low-, medium-, and high-density polyethylene, isotactic polypropylene, propylene-ethylene copolymer,
Polybutene-1, ethylene-propylene copolymer, ethylene-butene-1 copolymer, propylene-butene-1 copolymer, ethylene-propylene-butene-1 copolymer,
Olefin-based resins such as ethylene-vinyl acetate copolymers, ion-crosslinked olefin copolymers (ionomers) or blends thereof, and the like, polyacrylic acid, polymethacrylic acid, polyacrylamide, polyvinyl pyrrolidone, polyvinyl methyl ether, polyvinyl alcohol Vinyl alcohol-acrylic acid copolymer, modified polyethylene oxide, sodium acrylate polymer, starch grafted with acrylic acid (salt), acrylonitrile-grafted hydrolyzate of starch, starch such as cellulose grafted with acrylic acid (salt) A highly water-absorbing resin such as a cellulose-based graft derivative can be blended as a water-absorbing agent. In addition to these resins, inorganic salts such as sodium sulfate, magnesium sulfate, disodium phosphate and sodium diphosphate, organic compounds such as modified casein and modified starch, silica gel, alumina gel, diatomaceous earth, and various adsorbent inorganic materials such as zeolite Compounds can also be included.

As a gas barrier layer provided on the outer envelope,
Since the laminate on the resin layer side containing the oxygen absorbent is colored by the oxygen absorbent, it is preferable to use an opaque layer such as a metal foil or a vapor-deposited film of aluminum, tin, steel, tin, or the like. Since the other layer is preferably transparent from the viewpoint of the transparency of the contents, conventionally known gas barrier resins, such as, but not limited to, the ethylene-vinyl alcohol copolymer described above, polyvinyl chloride, and the like. Vinyl chloride resins such as polyvinylidene chloride, polyamide resins, SiOx-deposited polyethylene terephthalate, and the like can be suitably used.

As the heat sealing resin, any conventionally known heat sealing resin can be used. For example, but not limited to, low-, medium-, and high-density polyethylene, isotactic polypropylene, propylene-ethylene copolymer, polybutene-1, ethylene-
Propylene copolymer, ethylene-butene-1 copolymer,
An olefin-based resin such as a propylene-butene-1 copolymer and an ethylene-propylene butene-1 copolymer can be used. These resins may be colored with titanium white or the like as necessary.

Examples of the pinhole-resistant resin layer include nylon 6, nylon 6,6, nylon 6-6,6 copolymer, metaxylylene adipamide, nylon 6,10, nylon 11, nylon 12, nylon Polyamides such as 13, polyamides such as polyethylene terephthalate and polybutylene terephthalate, polycarbonates,
ABS resin, polyacetal, polymethyl methacrylate, isotactic polypropylene, polystyrene resin and the like can be suitably used. If sufficient adhesiveness cannot be obtained between the layers, use an adhesive resin made of a thermoplastic resin having a carbonyl group in the main chain or a side chain at a concentration of 1 to 700 milliequivalent / 100 g resin. Can be.

In a preferred embodiment of the present invention, a gas barrier layer (hereinafter referred to as an RG layer), a resin layer containing an oxygen absorbent (hereinafter referred to as an AO layer), a heat seal layer (hereinafter referred to as an HS layer), a pinhole-resistant The thickness of the layer (hereinafter referred to as RP layer) is R
G layer is 5 to 30 μm, AO layer is 20 to 70 μm, H
It is preferable that the S layer has a thickness of 5 to 100 μm and the RP layer has a thickness of 5 to 30 μm. Various changes can be made to the layer configuration of the sheet forming the outer wrapping bag as long as the sheet has a basic layer. For example, it can be formed by combining a first sheet and a second sheet having the following layer configuration. The AD layer indicates an adhesive layer. First sheet (outside) RG layer / AD layer / AO layer / AD layer / HS layer (inside) (outside) protective layer / RG layer / AD layer / AO layer / AD layer / H
S layer (inside) (outside) protective layer / AD layer / RG layer / AD layer / AO layer / H
S layer (inside) Second sheet (outside) RP layer / AD layer / RG layer / AD layer / HS layer (inside)

The outer bag used in the present invention can be produced by a method known per se except for having the above-mentioned layer constitution. After melt-kneading with an extruder corresponding to each resin layer, a lamination method such as dry lamination, sandwich lamination, and extrusion coating can be adopted. The formed laminated sheets are overlapped with each heat seal layer inside, and the periphery is heat-sealed by a conventionally known heat seal means such as a heat seal bar. In the present invention, the laminated sheets are heat-sealed while leaving the filling port of the inner packet, and after supplying the inner packet and moisture, the filling port of the inner packet is heat-sealed to seal the outer bag.

In the present invention, water is supplied into the outer wrapping bag before, during, or after filling the inner wrapping bag with the inner wrapping bag. The amount of water to be supplied to the outer wrapping bag is appropriately determined depending on the amount of the oxygen absorbent used in the outer wrapping bag.
1 to 3.0 g / liter, especially 0.3 to 2.0 g / liter
It is preferably in the liter range. If the water content is more than this range, water will remain in the outer bag, which may be misunderstood that the leakage of the inner solution has occurred. This is because the oxygen absorbent may not be able to sufficiently capture oxygen and may not be able to efficiently maintain the oxygen in the outer envelope at a low level.

As a method of supplying the water, the liquid may be supplied as it is into the outer wrapping bag, or may be supplied by spraying the water using a spray or the like. Further, the inside of the outer envelope may be replaced with humidified nitrogen, or moisture may coexist by filling with humidified nitrogen. When a label is attached to the outer surface of the inner package, moisture may be absorbed in the label in advance, or the label itself may be moistened with moisture. In this case, it is necessary that the label itself has water absorbency, and a highly water-absorbent resin capable of forming paper or a film as described above, or a label obtained by laminating these other resins with water or the like is used. It is preferable to use it by attaching it to a container such that the portion containing is the surface.

The outer bag of the present invention is, of course, not limited to this, and is suitably used for filling an infusion container used for infusion or the like. Generally, infusion containers are made of polyolefins such as polyethylene and polypropylene from the viewpoint of moisture resistance, hygiene and the like. Although these resins are excellent in moisture resistance, hygiene, etc., they are inferior in gas barrier properties,
As described above, the outer envelope bag of the present invention has excellent gas barrier properties and can effectively reduce the residual oxygen in the outer envelope bag, so that the solution inside the infusion container may be deteriorated by oxygen. Even if the contents are filled with a certain content, there is almost no oxygen in the outer bag, so that the inner solution can be stored without deterioration.

Infusions which may be deteriorated by oxygen include L-isoleucine, L-loin, L-lysine and L-lysine.
-Methionine, L-phenylalanine, L-threonine, L-valine, L-tyrosine, L-tryptophan,
L-arginine, L-histidine, L-alanine, L-
Cardiovascular agents such as those containing amino acid components such as asparagine sun, aminoacetic acid, L-proline, L-serine, sugars, lipids, vitamins, etc., and dobutamine hydrochloride and dopamine hydrochloride And their content modifiers. In the present invention, it is possible to produce an outer wrapping bag which can store these without alteration.

[0024]

【Example】

Example 1 An iron-based oxygen-absorbing composition having an average particle size of 25 μm was placed on the aluminum foil side of a laminated film composed of a polyethylene terephthalate film (12 μm) and aluminum foil (7 μm).
0% by weight of linear low density polyethylene (LLDP)
E) a 50 μm-thick oxygen-absorbing resin layer mainly composed of E) and further a 50 μm-thick titanium white-containing LLD on the outside thereof
First sheet with PE layer laminated, polyethylene terephthalate (PET) / ethylene vinyl alcohol copolymer (EVOH) / polyamide / polypropylene (PP)
The second laminated film having a total thickness of about 90 μm at 12: 15: 15: 50 was replaced with the L of the first laminated film.
The LDPE layer and the PP layer of the second laminated film are overlapped so that they face each other, and three sides are bonded together by heat sealing.
A bag of 0 × 150 mm was made. The bag was filled with 200 ml of water, filled with a PP flat bottle sealed under nitrogen replacement and 0.3 ml of water, and the bag was sealed and heat-sealed under nitrogen replacement. As a result, the inside of the bag and the inside of the PP bottle as the filling material have a low oxygen concentration. The nitrogen substitution rate was about 90%.

A control product was prepared in the same manner except that water was not added (control product 1), and a control product was prepared by using an LLDPE layer instead of the oxygen-absorbing layer and not adding water (control product 2). . These were stored under a storage condition of 22 ° C.-60% RH for a certain period, and the atmosphere gas composition inside the bag was measured by a gas chromatograph. As shown in Table 1, the oxygen concentration in the bag is found to decrease with time in the product of the present invention, but in the control product 1 not containing water, the concentration increase due to oxygen permeating from the second laminated film is suppressed, It cannot be reduced. Also, it can be seen that the oxygen concentration of Control 2 increases with time.

[0026]

[Table 1]

Example 2 Using the bag prepared in Example 1, a flat bottle, which is the contents of Example 1, was placed in a nitrogen atmosphere under floating fine water droplets, and sealed in the same manner as in Example 1. . 22 ℃ -60%
It was stored under RH storage conditions, and after a certain period of time, the gas composition inside the bag was analyzed with a gas chromatograph. The amount of water present in the initial bag was 0.3 g / 200 ml. The oxygen concentration in the bag decreased with time, and did not exceed the initial oxygen concentration even after 6 months.

Example 3 The flat bottle made of PP used in Example 1 was 60 × 100 mm
Was affixed using an adhesive, and hot water was sprayed on the label to make it wet. The water content was 30% by weight. It was placed in the three-side seal bag prepared in Example 1 and sealed under nitrogen replacement. The nitrogen substitution rate of the atmosphere in the bag was about 95%. The bag was stored at 22 ° C.-60% RH and the oxygen concentration in the bag was measured at regular intervals, and it was confirmed that the oxygen concentration in the bag decreased with time. Table 2 shows the results. As a control, a label having no water content was prepared, and the oxygen concentration was measured in the same manner.

[0029]

[Table 2]

Example 4 In the bottle made of PP used in Example 1, L-leucine and L-leucine were added.
-Isoleucine, lysine acetate, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, L-valine, L-arginine, L-histidine, L
-Filled with 200 ml of an amino acid preparation model solution in which alanine and glucose were dissolved in water, and sealed under nitrogen replacement. Next, the bag prepared in Example 1 was sealed together with 0.3 ml of water under a nitrogen atmosphere. The nitrogen substitution rate in the bag was 98%. After a certain period, the oxygen concentration in the bag and the color change of the contents in the PP bottle were examined. Table 3 shows the results. The oxygen concentration in the bag was lower than the initial oxygen concentration, and there was almost no color change of the contents, indicating good performance. As a control, the same bag was used, except that no oxygen absorbent layer was provided, and the same test was conducted.

[0031]

[Table 3]

[0032]

According to the present invention, a heat-sealing outer wrapper provided with an oxygen-absorbing agent-containing resin layer is filled with a plastic inner wrapper filled and sealed with contents, and is sufficient to activate the oxygen-absorbing agent. If the outer bag is sealed by heat sealing after allowing a sufficient amount of water to coexist, the permeation of oxygen from the outside can be effectively shut off without filling the outer bag with the plastic inner bag without performing retort sterilization etc. Oxygen remaining in the bag can be effectively captured, and a deoxygenated package excellent in the storage stability of the contents can be provided.

[Brief description of the drawings]

FIG. 1 is a diagram showing a change over time of the oxygen concentration in an outer envelope according to the amount of water in the outer envelope.

FIG. 2 is a sectional view showing an example of an outer bag used in the present invention.

FIG. 3 is a view showing a deoxygenated package in which an infusion container is accommodated in an outer package.

[Description of sign]

 DESCRIPTION OF SYMBOLS 1 Outer bag 2 First laminated sheet 3 Second laminated sheet 4 Housing part 5 Heat seal part 6a, 6b Heat seal layer 7 Oxygen absorbent compounded resin intermediate layer 8, 11 Gas barrier layer 9 Protective layer 12 Pinhole resistance Resin layer 13 Infusion container 14 Label

Continuation of the front page (51) Int.Cl. ⁶ identification code FI A61J 1/00 330B (56) References JP-A-4-295368 (JP, A) JP-A-4-282162 (JP, A) JP-A Sho 62-286463 (JP, A) JP-A-5-237162 (JP, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) A61J 1/10 B32B 27/00 B32B 27/18 B65D 77 / 04 B65D 81/20

Claims (8)

(57) [Claims] 1. A plastic inner package filled with contents and sealed is filled in a heat-sealable outer package provided with an oxygen-absorbing agent-containing layer, and an oxygen absorbent is activated between the outer package and the inner package. A method for producing a deoxygenated package, characterized in that, after a sufficient amount of water is allowed to coexist, the outer packaging bag is sealed by heat sealing. 2. The method according to claim 1, wherein 0.1 to 3.0 g / liter of water coexists based on the volume of the outer envelope. 3. The method according to claim 1, wherein moisture is coexisted by replacing the space between the outer envelope and the inner package with the humidified nitrogen or filling the humidified nitrogen. 4. The production method according to claim 1, wherein water is supplied between the outer packet and the inner packet in the form of droplets or spray to make water coexist. 5. The production method according to claim 1, wherein the inner package is a container having a label on an outer surface, and the label is made to absorb moisture or moistened with moisture in advance so that moisture coexists. 6. The production method according to claim 1, wherein the inclusion body is a polyolefin bottle. 7. The method according to claim 1, wherein the content is an amino acid preparation or a cardiovascular agent. 8. A first laminated sheet in which an outer envelope bag has a gas barrier layer, an oxygen absorbent-containing resin intermediate layer and a heat sealable resin inner layer, a pinhole resistant resin layer, a gas barrier layer and a heat sealable resin. The production method according to claim 1, wherein the transparent second laminated sheet having an inner layer is overlapped so that the heat-sealable resin layers face each other, and the bag is formed by heat sealing.