JP5428157B2 - Packaging bag for prefilled syringe - Google Patents

Description

  The present invention relates to a packaging bag made of a laminated film having gas barrier properties for packaging a prefilled syringe, and a method for producing the same. In more detail, this invention relates to the said packaging bag which consists of a laminated | multilayer film which has other physical properties suitable as a packaging bag of a prefilled syringe while having high oxygen gas barrier property and suitable water vapor | steam barrier property.

Prefilled syringes pre-filled with drugs can save time and labor for transferring drugs from ampoules to syringes, and can prevent contamination by bacteria and foreign substances. ing.
Since the prefilled syringe takes time from the time when the medicine is filled in the syringe until administration, the syringe container is required to have a high oxygen gas barrier property for preventing the oxidative decomposition of the medicine.

  In recent years, syringe containers have been switched from glass to plastic because of their ease of handling. For example, Patent Document 1 describes a plastic prefilled syringe syringe. However, the plastic syringe container has the disadvantage that the gas barrier property is inferior to that made of glass, instead of having the advantage of being light and free from damage. Therefore, a prefilled syringe using a plastic syringe container needs to be packaged with a packaging bag having a high oxygen gas barrier property, and further, an oxygen scavenger needs to be sealed inside in order to remove oxygen in the packaging bag.

  In order to manufacture such a packaging bag for prefilled syringes, for example, a gas barrier laminated film comprising three or more layers such as a polyester film layer / nylon film layer / heat-sealable resin layer on which an inorganic oxide is deposited. Can be used. In addition, with the improvement in gas barrier properties of polyester-based vapor-deposited polyester film, the nylon film layer is omitted, and a two-layer type consisting of a polyester film layer deposited with an inorganic oxide / heat-sealable resin layer Gas barrier laminated films have also been used.

  A gas barrier laminate film using a polyester-based vapor deposition film has the advantage that it can easily obtain good adhesion between the substrate and the vapor deposition surface, but its physical properties are as a packaging bag for prefilled syringes. Is unsuitable. That is, when the prefilled syringe is accommodated and sealed in the packaging bag, the oxygen in the packaging bag is removed by the oxygen scavenger, so that the packaging bag is in a low vacuum state. Therefore, the film of the packaging bag bends at a steep angle along the shape of the syringe, particularly at the bottom of the prefilled syringe and the portion in contact with the plunger, and strong wrinkles are generated. However, the gas barrier laminated film based on polyester lacks flexibility, and the packaging bag for prefilled syringes made of this has a gas barrier property because the inorganic oxide vapor-deposited film is broken as the film is deformed or bent. It may be damaged or, in some cases, broken.

  Moreover, it is known that a plastic syringe container generally allows a small amount of moisture to pass therethrough. Unlike oxygen gas permeation, this does not have an adverse effect on internal chemicals, but a packaging bag made of a conventional gas barrier laminate film using a polyester-based vapor deposition film has its water vapor content. Since the barrier ability is too high, there is a problem that moisture that has permeated out of the plastic syringe container is condensed in the bag, resulting in poor appearance.

Furthermore, a packaging bag made of a laminated film having a polyester film as the outermost layer has a problem in cutability and is generally difficult to open.
JP-A-2002-253641

  The present invention comprises a two-layer gas barrier laminate film, has a high oxygen gas barrier property and a suitable water vapor barrier property, and is suitable for packaging a prefilled syringe. The present invention provides a packaging bag for a prefilled syringe having a cutting property.

  The present inventors have intensively studied to solve the above problems, and for a prefilled syringe comprising a two-layer gas barrier laminate film having desired gas barrier properties, flexibility, transparency, strength, and easy-cut properties. As a packaging bag, one or more inorganic oxide vapor deposition films are laminated on one surface of a biaxially stretched polyamide resin film, and a heat-sealable resin layer is laminated on the inorganic oxide vapor deposition film. We have developed a packaging bag for prefilled syringes that can be obtained by bag-making the laminated film. Moreover, by providing a barrier coat between the inorganic oxide vapor-deposited film and the heat-sealable resin layer, a packaging bag with further improved oxygen barrier properties could be obtained.

  The laminated film constituting the packaging bag for the prefilled syringe of the present invention is a two-layer gas barrier laminated film comprising a biaxially stretched polyamide resin film layer / heat-sealable resin layer on which an inorganic oxide is deposited, It is less costly than a conventional gas barrier laminate film composed of three or more layers, can be easily manufactured, exhibits high oxygen gas barrier properties, and has good flexibility and strength. Therefore, it is strong against bending and deformation, and even if it comes into contact with the bottom of the barrel of the prefilled syringe or the plunger, the gas barrier property does not deteriorate due to the rupture of the inorganic oxide deposited film. Therefore, high oxygen gas barrier properties can be maintained over a long period of time.

  Moreover, the said laminated | multilayer film has water vapor | steam barrier property suitable as a packaging bag for prefilled syringes. Specifically, since the water vapor barrier property is not too high, a very small amount of moisture that has permeated out of the prefilled syringe can permeate out of the packaging bag to prevent condensation.

  Furthermore, since the laminated film is excellent in easy-cutting properties, the packaging bag for prefilled syringes of the present invention comprising this can be easily opened.

The present invention will be described in more detail below with reference to the drawings.
<1> Layer structure of laminated film constituting packaging bag for prefilled syringe of the present invention First, the layer structure of the laminated film used in the present invention will be described. FIG. 1 is a cross-sectional view showing an example of a layer structure of a laminated film constituting a packaging bag for a prefilled syringe according to the present invention.
As shown in FIG. 1, the laminated film according to the present invention has an inorganic oxide vapor-deposited film 2 and a heat-sealable resin layer 3 in order on one surface of a biaxially stretched polyamide resin film 1 as a base film. The stacked structure is the basic structure.
Moreover, in this invention, as shown in FIG. 2, you may provide the barrier coat 4 between the inorganic oxide vapor deposition film 2 and the heat-sealable resin layer 3. As shown in FIG.
In the present invention, the inorganic oxide vapor deposition film may be a single layer or a multilayer composed of two or more layers.

<2> Substrate Film In the present invention, a biaxially stretched polyamide resin film excellent in impact resistance, puncture resistance, and flex resistance is used as the substrate film that supports the inorganic oxide vapor deposition film.
As such a biaxially stretched polyamide resin film, any biaxially stretched polyamide resin film can be used as long as it can be satisfactorily maintained without impairing the properties of the inorganic oxide deposited film and barrier coat described later. For example, nylon 6, nylon 66, nylon 610, nylon 612, nylon 11, nylon 12, and other various polyamide-based resin films can be used. These resin films are preferably stretched in the biaxial direction, and the thickness is about 10 to 50 μm, preferably about 10 to 25 μm. The surface of the resin film can be optionally subjected to surface activation treatment such as corona treatment, plasma treatment, flame treatment, etc., if necessary. In the present invention, in order to increase the adhesion strength with the inorganic oxide vapor deposition film, for example, a polyester-based, urethane-based, epoxy-based or amine-based anchor coat agent is deposited to form the inorganic oxide vapor-deposited film. It can also be used in-line or off-line in the process. Furthermore, in the present invention, desired additives such as an antistatic agent, an ultraviolet absorber, a plasticizer, a lubricant, and a filler are optionally added within a range that does not affect the transparency. Polyamide resin films containing them can also be used.

<3> Inorganic oxide vapor deposition film In this invention, as an inorganic oxide vapor deposition film, silicon (Si), aluminum (Al), magnesium (Mg), calcium (Ca), potassium (K), tin (Sn), A vapor deposition film made of an oxide such as sodium (Na), boron (B), titanium (Ti), lead (Pb), zirconium (Zr), yttrium (Y) can be given.
Preferable examples include a deposited film made of a metal oxide of silicon (Si) or aluminum (Al).

The metal oxide vapor deposition film can also be referred to as a metal oxide such as silicon oxide, aluminum oxide, magnesium oxide, and the like, for example, SiO _x , AlO _x , MgO. _It is represented by MO _x (wherein, M represents a metal element, and the value of x varies depending on the metal element), such as x.

  In addition, as a range of the value of x described above, silicon (Si) is 0 to 2, aluminum (Al) is 0 to 1.5, magnesium (Mg) is 0 to 1, calcium (Ca) is 0 to 1, potassium (K) is 0 to 0.5, tin (Sn) is 0 to 2, sodium (Na) is 0 to 0.5, boron (B) is 0 to 1.5, titanium (Ti) is 0 to 2, Lead (Pb) can take values in the range of 0 to 1, zirconium (Zr) in the range of 0 to 2, and yttrium (Y) in the range of 0 to 1.5.

In the above, when x = 0, it is a perfect metal and cannot be used because it is not transparent. Further, the upper limit of the range of x is a value when completely oxidized.
Desirably, silicon (Si) having a value in the range of 1.0 to 2.0 and aluminum (Al) in the range of 0.5 to 1.5 can be used.

Although the film thickness of an inorganic oxide vapor deposition film changes with the kind of metal to be used or a metal oxide, etc., it can be arbitrarily selected, for example in the range of 5-100 nm, Preferably it is 10-50 nm.
Moreover, the metal to be used or an oxide of a metal can be used by 1 type, or 2 or more types of mixtures as an inorganic oxide vapor deposition film, and the inorganic oxide vapor deposition film mixed by the dissimilar material can also be comprised.

  Further, when the inorganic oxide is silicon oxide, it may be a carbon-containing silicon oxide represented by SiOxCy [wherein x is in the range of 1.5 to 2.2, and y is Preferably it is in the range of 0.15 to 0.80, and x is in the range of 1.7 to 2.1 and y is in the range of 0.39 to 0.47. preferable].

<4> Vapor Deposition Method In the present invention, in order to obtain a desired gas barrier property, the inorganic oxide vapor-deposited film is formed by a chemical vapor deposition method (chemical vapor deposition method, CVD method), preferably a plasma chemical vapor deposition method. It is formed.
In the present invention, specifically, a vapor deposition monomer gas such as an organosilicon compound is used as a raw material on the surface of the base film, and an inert gas such as argon gas or helium gas is used as a carrier gas. A vapor deposition film made of an oxide can be formed by using a low temperature plasma chemical vapor deposition method using an oxygen gas or the like as an oxygen supply gas and using a low temperature plasma generator or the like.
In the above, as the low-temperature plasma generator, for example, generators such as high-frequency plasma, pulse wave plasma, microwave plasma can be used, but in the present invention, in order to obtain a highly active stable plasma, It is desirable to use a high frequency plasma generator.

  An example of the method for forming an inorganic oxide vapor deposition film by the low temperature plasma chemical vapor deposition method in the present invention will be described. FIG. 3 is a schematic configuration diagram of a low-temperature plasma chemical vapor deposition apparatus used in the above-described plasma chemical vapor deposition method.

  In the present invention, as shown in FIG. 3, the base film 1 is unwound from an unwinding roll 23 disposed in the vacuum chamber 22 of the low temperature plasma chemical vapor deposition apparatus 21, It is conveyed on the circumferential surface of the cooling / electrode drum 25 through the auxiliary roll 24 at a predetermined speed. Oxygen gas, inert gas, monomer gas for vapor deposition, and the like are supplied from the gas supply devices 26 and 27 and the raw material volatilization supply device 28, and a vacuum chamber is formed through the raw material supply nozzle 29 while adjusting a mixed gas composition for vapor deposition. The mixed gas composition for vapor deposition is introduced into 22, and plasma is generated by glow discharge plasma 30 on the substrate film 1 conveyed on the cooling / electrode drum 25 peripheral surface. To form an inorganic oxide deposited film. At that time, the cooling / electrode drum 25 is applied with a predetermined power from a power source 31 disposed outside the vacuum chamber 22, and a magnet 32 is disposed in the vicinity of the cooling / electrode drum 25. The generation of plasma is promoted. Next, the base film 1 is wound around a winding roll 34 via an auxiliary roll 33 after an inorganic oxide vapor deposition film is formed on one surface thereof. In the figure, 35 represents a vacuum pump.

  Although not shown, in the present invention, the layer of the inorganic oxide vapor-deposited film may be a single layer or a multilayer composed of two or more layers, and the oxide used may be used alone. You may use it as a mixture of 2 or more types.

  Polyamide-based resin films are generally known to be inferior to polyester films in adhesion to inorganic oxide vapor-deposited films, but in the present invention, the surface of the base film is cleaned by plasma, Since polar groups, free radicals, and the like are generated on the surface of the material film, strong adhesion between the formed inorganic oxide vapor-deposited film and the polyamide-based resin film as the substrate can be obtained.

  In the low temperature plasma chemical vapor deposition apparatus described above, the inorganic oxide vapor deposition film is formed into a thin film on the base film by using the plasma source gas, so that it is dense and has few gaps. It becomes a continuous layer rich in flexibility.

  Therefore, it is possible to prevent the inorganic oxide vapor-deposited film from being broken due to the deformation and bending of the film, and in combination with the properties of the biaxially stretched polyamide resin film having excellent impact resistance, bending resistance, etc. A gas barrier laminate film preferable for use as a packaging bag for a prefilled syringe having a shape can be obtained.

<5> Barrier coat In the present invention, a barrier coat obtained by further applying a gas barrier composition obtained by polycondensation of an alkoxide and a water-soluble polymer by a sol-gel method on the inorganic oxide vapor-deposited film. Can be provided. Thereby, oxygen gas barrier property can further be improved.

As the alkoxide that can be used in the gas barrier composition, the general formula R ¹ _n M (OR ² ) _m (wherein R ¹ and R ² are organic groups having 1 to 8 carbon atoms, and M is a metal atom) And n is an integer of 0 or more, m is an integer of 1 or more, and n + m is a valence of M).
As the water-soluble polymer, either a polyvinyl alcohol resin or an ethylene / vinyl alcohol copolymer or both can be preferably used.

In the present invention, as the metal atom M, silicon, zirconium, titanium, aluminum or the like can be used as the alkoxide represented by the general formula R ¹ _n M (OR ² ) _m . Moreover, in this invention, the alkoxide of a single or 2 or more types of different metal atoms can be mixed and used in the same solution.

In the alkoxide represented by the general formula R ¹ _n M (OR ² ) _m , specific examples of the organic group represented by R ¹ include, for example, a methyl group, an ethyl group, an n-propyl group, i Examples include -propyl group, n-butyl group, i-butyl group, sec-butyl group, t-butyl group, n-hexyl group, n-octyl group and other alkyl groups.

In the alkoxide represented by the general formula R ¹ _n M (OR ² ) _m , specific examples of the organic group represented by R ² include, for example, a methyl group, an ethyl group, an n-propyl group, i -Propyl group, n-butyl group, sec-butyl group and the like.
In the present invention, these alkyl groups may be the same or different in the same molecule.

  Moreover, in this invention, it is preferable that content of a polyvinyl alcohol-type resin and / or an ethylene vinyl alcohol copolymer is the range of 5-500 weight part with respect to 100 weight part of total amounts of said alkoxide. In the above, if it exceeds 500 parts by weight, the brittleness of the barrier coating is increased, and the weather resistance and the like are also deteriorated.

  In the present invention, as the polyvinyl alcohol-based resin, generally obtained by saponifying polyvinyl acetate can be used. Specific examples include RS-110 (degree of saponification = 99%, degree of polymerization = 1,000), an RS polymer manufactured by Kuraray Co., Ltd., and Kuraray Poval LM-20SO (degree of saponification = 40%, degree of polymerization = manufactured by Kuraray Co., Ltd.). 2000), Gohsenol NM-14 manufactured by Nippon Synthetic Chemical Industry Co., Ltd. (degree of saponification = 99%, degree of polymerization = 1,000), and the like can be used.

  In the present invention, as the ethylene-vinyl alcohol copolymer, a saponified product of a copolymer of ethylene and vinyl acetate, that is, a product obtained by saponifying an ethylene-vinyl acetate random copolymer should be used. Can do. Specific examples include Kuraray Co., Ltd., Eval EP-F101 (ethylene content; 32 mol%), Nippon Synthetic Chemical Industry Co., Ltd., Soarnol D2908 (ethylene content; 29 mol%), and the like.

  In the present invention, in order to prepare a gas barrier composition for forming a barrier coat according to the present invention, for example, a silane coupling agent such as a known organic reactive group-containing organoalkoxysilane can also be added.

<6> Barrier Coat Forming Method The gas barrier composition used in the present invention is a polycondensation of an alkoxide and a water-soluble polymer by a sol-gel method in the presence of a sol-gel method catalyst, acid, water and an organic solvent. It can be prepared by coating on an inorganic oxide vapor-deposited film provided on a biaxially stretched polyamide resin film as a base film, and is 20 ° C. to 200 ° C., preferably 140 ° C. or higher. And a barrier coat can be formed by heat-processing for 10 second-10 minutes at the temperature below melting | fusing point of a base film. If necessary, the surface of the deposited inorganic oxide film may be plasma-treated with oxygen gas.
In addition, a barrier coat may form a composite polymer layer by superposing two or more layers.

  The sol-gel method catalyst used in the preparation of the gas barrier composition is a tertiary amine that is substantially insoluble in water and soluble in an organic solvent, such as N, N-dimethylbenzylamine. As the acid, for example, mineral acids such as sulfuric acid, hydrochloric acid, and nitric acid, and organic acids such as acetic acid and tartaric acid, and the like can be used. Furthermore, as an organic solvent, methyl alcohol, ethyl alcohol, etc. can be used, for example.

Further, regarding the gas barrier composition, the polyvinyl alcohol resin and / or the ethylene / vinyl alcohol copolymer is preferably in a state of being dissolved in a coating solution containing the alkoxide, the silane coupling agent, or the like. Therefore, the type of the organic solvent is appropriately selected. In the present invention, as the ethylene / vinyl alcohol copolymer solubilized in a solvent, for example, those commercially available as Soarnol (manufactured by Nippon Synthetic Chemical Co., Ltd.) can be used.
When the above gas barrier composition is applied onto an inorganic oxide vapor deposition film and heated to remove the solvent and the alcohol produced by the polycondensation reaction, the polycondensation reaction is completed and a transparent barrier coat is formed. .

  Furthermore, since the hydroxyl group generated by hydrolysis and the organic reactive group of the silane coupling agent are bonded to the hydroxyl group on the surface of the inorganic oxide deposition film, the adhesion and adhesion between the inorganic oxide deposition film and the barrier coat Etc. are good.

  By being formed as described above, the barrier coat of the present invention has a structure in which a linear polymer having crystallinity is included and a large number of minute crystals are embedded in an amorphous portion. Such a crystal structure is the same as that of a crystalline organic polymer (for example, vinylidene chloride or polyvinyl alcohol), and a polar group (OH group) is partially present in the molecule, and the molecular cohesive energy is high. Excellent rigidity due to high oxygen gas barrier properties.

  In the present invention, the inorganic oxide vapor deposition film and the barrier coat form, for example, a chemical bond by hydrolysis / co-condensation, a hydrogen bond, or a coordination bond, and the adhesion between these two layers is improved. Due to the synergistic effect, a better barrier effect can be exhibited.

  In the present invention, the gas barrier composition may be applied by one or more times by a coating means such as a roll coat such as a gravure roll coater, a spray coat, dipping, a brush, a bar coat, or an applicator. With this coating, a barrier coat having a dry film thickness of 0.01 to 30 μm, preferably 0.1 to 10 μm can be formed. Furthermore, condensation is performed by heating and drying at a temperature of 50 to 300 ° C. for 0.05 to 60 minutes under a normal environment, and the barrier coat of the present invention can be formed.

  In this invention, after providing a vapor deposition layer and a barrier coat on a biaxially stretched polyamide resin film, a vapor deposition layer may be further provided, and the barrier coat may be formed on the vapor deposition layer in the same manner as described above. Thus, by increasing the number of stacked layers, the gas barrier property can be further improved.

<7> Heat-sealable resin layer In the present invention, as the heat-sealable resin constituting the heat-sealable resin layer, it is possible to use a resin having heat-sealability that can be melted by heat and fused to each other. Specifically, for example, low density polyethylene, medium density polyethylene, high density polyethylene, linear (linear) low density polyethylene, polypropylene, ethylene-vinyl acetate copolymer, ionomer resin, ethylene-acrylic acid copolymer. Polymers, ethylene-ethyl acrylate copolymers, ethylene-methacrylic acid copolymers, ethylene-methyl methacrylate copolymers, ethylene-propylene copolymers, methylpentene polymers, polybutene polymers, polyolefins such as polyethylene or polypropylene Resin is acrylic acid, methacrylic acid, maleic acid Various resins such as acid-modified polyolefin resins modified with unsaturated carboxylic acids such as maleic anhydride, fumaric acid, and itaconic acid, polyvinyl acetate resins, poly (meth) acrylic resins, and polyvinyl chloride resins are used. can do. In the present invention, the heat-sealable resin layer can be composed of a resin film or sheet as described above, or a coating film made of a resin composition mainly composed of the resin as described above. The thickness is preferably about 5 μm to 300 μm, and more preferably about 10 μm to 100 μm.

<8> Lamination method of heat-sealable resin layer In the present invention, the heat-sealable resin layer is provided on the inorganic oxide vapor-deposited film or, when a barrier coat is provided, on the barrier coat via a laminating adhesive. In addition, it can be carried out by a usual laminating method, for example, a wet lamination method, a dry lamination method, an extrusion lamination method or the like.

  Examples of the laminating adhesive that can be used in the present invention include polyvinyl acetate adhesives, homopolymers such as ethyl acrylate, butyl, 2-ethylhexyl ester, and methyl methacrylate, acrylonitrile. Polyacrylic acid ester adhesives, copolymers of styrene, etc., cyanoacrylate adhesives, copolymers of ethylene and monomers such as vinyl acetate, ethyl acrylate, acrylic acid, methacrylic acid, etc. Ethylene copolymer adhesives, cellulose adhesives, polyester adhesives, polyamide adhesives, polyimide adhesives, amino resin adhesives made of urea resin or melamine resin, phenol resin adhesives, epoxy adhesives Agent, polyurethane adhesive, reactive (meth) acrylic adhesive , Chloroprene rubber, nitrile rubber, styrene - butadiene rubber consisting of such as a rubber-based adhesive, silicone adhesive, an alkali metal silicate, the use of adhesives inorganic adhesive or the like made of a low-melting-point glass or the like Tekiru.

  The composition system of the above-mentioned adhesive may be any composition form such as an aqueous type, a solution type, an emulsion type, and a dispersion type, and the property is any of film / sheet form, powder form, solid form, etc. Further, the bonding mechanism may be any of a chemical reaction type, a solvent volatilization type, a heat melting type, and a hot pressure type.

Thus, the adhesive can be applied, for example, by a coating method such as a roll coating method, a gravure roll coating method, a kiss coating method, a printing method, or the like. A position of 0.0 g / m ² (dry state) is desirable.

  In the present invention, when performing the lamination as described above, if necessary, for example, pretreatment such as corona discharge treatment, ozone treatment, flame treatment, plasma treatment or the like is performed on the surface of each film to be laminated. It can be applied arbitrarily.

<9> Physical Properties Next, factors for setting the gas barrier properties required for the laminated film constituting the packaging bag of the present invention will be described.
In order to suppress the deterioration of the quality of the medicine in the plastic syringe container, the laminated film constituting the packaging bag of the present invention is 5 ml / m ² · as a numerical value obtained by a method based on JIS K 7126 regarding oxygen permeability. Excellent oxygen barrier properties of 24 hours · MPa or less can be exhibited.

On the other hand, the laminated film constituting the packaging bag of the present invention is JIS K 7129 in terms of water vapor permeability so that a very small amount of moisture permeated from the plastic syringe container can permeate outside the packaging bag and prevent condensation. As a numerical value obtained by the method based on the above, a suitable water vapor barrier property of 2.0 g / m ² · day or more and 10.0 g / m ² · day or less can be shown. When the water vapor transmission rate is lower than 2.0 g / m ² · day, moisture is condensed in the packaging bag, causing an appearance defect. On the other hand, if it is higher than 10.0 g / m ² · day, the drug is dried, which is not preferable.

<10> Packaging Bag for Prefilled Syringe Next, in the present invention, a method for producing a laminated film according to the present invention as described above and manufacturing a packaging bag for a prefilled syringe according to the present invention will be described. For example, using the laminated film according to the present invention produced by the method as described above, facing the heat-sealable resin layer, folding it, or overlapping the two sheets, and the periphery The end portion can be heat-sealed to provide a seal portion, and packaging bags having various forms can be manufactured.

  In the above, as a heat sealing method, for example, a known method such as a bar seal, a rotary roll seal, a belt seal, an impulse seal, a high frequency seal, and an ultrasonic seal can be used.

  In the actual work, an insertion port for inserting the prefilled syringe as the contents is left, and the other peripheral edge is formed by heat fusion. Then, the prefilled syringe is filled and the insertion port is closed by heat fusion. More specifically, the prefilled syringe is inserted from the opening of the packaging bag of the present invention, and then the opening is sealed by heat sealing or the like while performing nitrogen gas replacement or the like, for example. The prefilled syringe package product packaged in the prefilled syringe packaging bag can be manufactured.

The packaging bag for prefilled syringes of the present invention has an excellent oxygen gas barrier property based on the characteristics of the laminated film as a constituent component, and further has excellent flexibility, transparency, strength, tearability and the like. Therefore, the oxidative decomposition of the chemical | medical agent in a prefilled syringe can be prevented, and even if it contacts the angular part of a syringe container, an inorganic oxide vapor deposition film does not fracture | rupture. Therefore, high oxygen gas barrier properties can be maintained over a long period of time. Furthermore, the packaging bag of this invention has the water vapor | steam barrier property suitable for packaging a prefilled syringe, and can prevent that dew condensation arises in a packaging bag.
Next, the present invention will be specifically described with reference to examples.

[Example 1]
A silicon oxide vapor deposition layer having a thickness of 10 nm was formed on one surface of a biaxially stretched nylon film having a thickness of 15 μm by using a plasma chemical vapor deposition method. Next, the following barrier coat forming composition was applied on the silicon oxide vapor-deposited layer by a gravure coating method, and dried at 150 ° C. for 1 minute to form a barrier coat composed of a composite polymer layer having a thickness of 0.3 μm. .
A low-density polyethylene film having a thickness of 50 μm is dry-laminated on the barrier coat of the gas-barrier transparent vapor-deposited nylon film obtained above via a dry laminating adhesive, thereby biaxially stretched nylon film 15 μm / silicon oxide vapor-deposited A laminated film of 10 nm layer / barrier coat 0.3 μm / low density polyethylene film 50 μm was prepared.

Next, the laminated film was folded with the surfaces of the low-density polyethylene film facing each other, leaving an insertion port for containing a prefilled syringe, and the other peripheral edges were bag-formed by heat sealing.
Next, 100 g of glycyrrhizin ammonium salt, 800 g of glycine and 30 g of L-cysteine are dissolved in 50 L of water, and a prefilled syringe filled and sealed with a solution obtained by filtering this is inserted into the packaging bag and sealed. A packaging bag containing a prefilled syringe was obtained.

<Preparation of composition for forming barrier coat>
34.13 g of ethyl silicate, 25 g of ethanol, 1.15 g of 2N hydrochloric acid and 4.58 g of water were mixed and stirred at room temperature for about 1 hour, then 3.41 g of epoxysilane SH6040 (manufactured by Toray Dow Corning), 30 L of Soarnol (Nippon Synthesis) Chemical Co., Ltd. (31.56 g) and N, N-dimethylbenzylamine (0.17 g) were added and stirred for 30 minutes to obtain a barrier coat forming composition.

[Comparative Example 1]
A packaging bag containing a prefilled syringe was produced in the same manner as in Example 1 except that a biaxially stretched polyester film having a thickness of 12 μm was used as the base film instead of the biaxially stretched nylon film.

[Comparative Example 2]
In the same manner as in Example 1, a silicon oxide vapor deposition layer was formed on one surface of a biaxially stretched polyester film having a thickness of 12 μm. Next, a laminated film in which a biaxially stretched nylon film having a thickness of 15 μm and a low-density polyethylene film having a thickness of 50 μm were sequentially laminated on the silicon oxide vapor-deposited layer by a dry laminating method was prepared. The bag was made in the same manner as above.

  Next, 100 g of glycyrrhizin ammonium salt, 800 g of glycine and 30 g of L-cysteine are dissolved in 50 L of water, and a prefilled syringe filled with a solution obtained by filtering this is inserted into the packaging bag and sealed. A packaging bag containing a prefilled syringe was obtained.

<Evaluation method>
1. The oxygen and water vapor permeability of the packaging bags obtained in the examples and comparative examples were implemented using the MOCON method (JIS K7126, JIS K7129).
2. Cuts were made in the sealing portions of the packaging bags obtained in the examples and comparative examples, the portions were torn by hand, and the cutting properties of the packaging bags were evaluated. The evaluation was performed in three stages: ○: cleanly torn linearly, Δ: slightly cut portion meandered, and x: cut portion greatly meandered.
3. The prefilled syringe-containing packaging bags obtained in the examples and comparative examples were stored in a constant temperature and humidity chamber at 40 ° C. and 80% RH for 1 month, and the appearance inside the bags was confirmed.
4). Since decomposition of L-cysteine in the solution is promoted in the presence of oxygen, the content of L-cysteine in the solution in the prefilled syringe was used as an index of the amount of oxygen permeation to the packaging bag during the storage test. . For evaluation, the prefilled syringe-containing packaging bags obtained in Examples and Comparative Examples were allowed to stand at room temperature for 1 month, then 10 bags were packed in a paper box and vibrated 1000 times with a vibration tester, and then room temperature or 40 ° C. The sample was stored under the following conditions, and the L-cysteine content was changed over time.

<Result>
The results were as follows.

<Evaluation>
As apparent from Table 2 above, the packaging bag according to the present invention obtained in Example 1 has excellent easy-cutting properties, has a water vapor barrier property suitable for packaging a prefilled syringe, A beautiful appearance was maintained without generating water droplets in the packaging bag. Further, as is apparent from Table 3, it has excellent bending resistance and maintains a high oxygen gas barrier property without breaking the gas barrier layer even when it comes into contact with the barrel of the prefilled syringe or the protrusion of the plunger. I was able to. Furthermore, it has excellent impact resistance, and even if it continues to receive external impacts, no deterioration in gas barrier properties was observed.
On the other hand, the packaging bags obtained in Comparative Examples 1 and 2 are both difficult to cut, and the water vapor barrier property is too high, so water droplets were generated inside the bag. In both cases, the gas barrier layer was broken due to wrinkles and bending caused by sealing at the contact portion with the protrusion of the prefilled syringe, and the oxygen gas barrier property was lowered. Further, the gas barrier layer was further broken by the impact from the outside, and the oxygen gas barrier property was significantly lowered with time.

It is a schematic sectional drawing which shows the layer structure of the laminated film which comprises the packaging bag which concerns on this invention. It is a schematic sectional drawing which shows the layer structure of the laminated film which comprises the packaging bag which concerns on this invention. It is a schematic block diagram which shows the outline | summary of the example about a plasma chemical vapor deposition apparatus.

Claims (9)

A laminated film in which one or more inorganic oxide vapor-deposited films are laminated on one surface of a biaxially stretched polyamide resin film, and a heat-sealable resin layer is laminated on the inorganic oxide vapor-deposited film; Is a packaging bag for prefilled syringes obtained by making a bag with a water vapor transmission rate of 2.0 g / m ² · day or more and 10.0 g / m obtained by a method based on JIS K 7129 ^{2. The} above packaging bag, which is ² · day or less .   The packaging bag according to claim 1, wherein the biaxially stretched polyamide resin film is a biaxially stretched nylon film.   The packaging bag of Claim 1 or 2 with which the inorganic oxide vapor deposition film was laminated | stacked by the plasma chemical vapor deposition method.   The packaging bag of any one of Claims 1-3 whose inorganic oxide which comprises an inorganic oxide vapor deposition film is a silicon oxide or an aluminum oxide.   The packaging bag according to any one of claims 1 to 4, wherein the heat-sealable resin layer comprises a polyolefin-based resin layer having heat-sealability.   A barrier coat formed by applying a gas barrier composition obtained by polycondensation of an alkoxide and a water-soluble polymer by a sol-gel method is provided between the inorganic oxide vapor-deposited film and the heat-sealable resin layer. The packaging bag of any one of -5. The alkoxide has the general formula R ¹ _n M (OR ² ) _m (wherein R ¹ and R ² are organic groups having 1 to 8 carbon atoms, M is a metal atom, and n is an integer of 0 or more. , M is an integer of 1 or more, and n + m is a valence of M), and the water-soluble polymer is a polyvinyl alcohol resin or ethylene / vinyl alcohol The packaging bag according to claim 6, which is either or both of a copolymer. The packaging bag according to any one of claims 1 to 7, wherein the heat-sealable resin layer is laminated via an adhesive for laminating. The packaging bag according to any one of claims 1 to 8, wherein a numerical value obtained by a technique based on JIS K 7126 is 5 ml / m ² · 24 hours · MPa or less.

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