MEDICAL GLASS CONTAINER AND METHOD FOR MANUFACTURING SAME

Abstract

A medical glass container, a coat is formed on at least a part of an inner wall of the glass container, wherein the coat is a diamond-like carbon film that does not contain silicon.

Claims

1. A medical glass container comprising a coat formed on at least a part of an inner wall of a glass container, wherein the coat is a silicon-free diamond-like carbon film.

2. The medical glass container according to claim 1, wherein the coat is a silicon-free and fluorine-containing diamond-like carbon film or a silicon-free and fluorine-free diamond-like carbon film.

3. The medical glass container according to claim 1, wherein a silicon-containing intermediate layer is provided between a glass surface of the inner wall of the glass container and the coat.

4. The medical glass container according to claim 1, wherein at least a part of the glass surface of the inner wall of the glass container is hydrophilized.

5. The medical glass container according to claim 1, wherein glass forming the glass container is borosilicate glass, aluminosilicate glass, or soda lime glass.

6. The medical glass container according to claim 1, wherein the glass container is a vial, an injector barrel, a syringe with needle, and a cartridge type syringe.

7. The medical glass container according to claim 6, wherein the glass container is a vial, the medical glass container further has a rubber stopper, and at least a part of an inner surface of the rubber stopper is coated with a diamond-like carbon film or a fluororesin film.

8. The medical glass container according to claim 6, wherein the glass container is an injector barrel, the medical glass container further has a gasket-mounted plunger, and at least a part of a surface of the gasket is coated with a diamond-like carbon film.

9. The medical glass container according to claim 6, wherein the glass container is an injector barrel, the medical glass container further has a gasket-mounted plunger, and a fluororesin film is bonded to at least a face of a surface of the gasket adjoining with the inner surface of the injector barrel.

10. The medical glass container according to claim 2, wherein the coat is a silicon-free and fluorine-containing diamond-like carbon film, and a transmittance of the glass container at 450 nm is 90% or higher.

11. A method for manufacturing a medical glass container having a coat formed on at least a part of an inner wall of the glass container, the method comprising a process of forming a silicon-free diamond-like carbon film as the coat by plasmatizing a hydrocarbon-based gas that does not contain silicon as a constituent element inside a storage space of the glass container.

12. The method for manufacturing the medical glass container according to claim 11, wherein the hydrocarbon-based gas that does not contain silicon is a mixed gas of a first hydrocarbon-based gas that does not contain fluorine or silicon as a constituent element and a second hydrocarbon-based gas that is modified with fluorine and does not contain silicon as a constituent element, and the coat is a silicon-free/fluorine-containing diamond-like carbon film.

13. The method for manufacturing the medical glass container according to claim 11, wherein the hydrocarbon-based gas that does not contain silicon is a first hydrocarbon-based gas that does not contain fluorine or silicon as a constituent element, and the coat is a silicon-free/fluorine-free diamond-like carbon film.

14. The method for manufacturing the medical glass container according to claim 12, wherein the first hydrocarbon-based gas is acetylene and/or methane.

15. The method for manufacturing the medical glass container according to claim 12, wherein a gas volume ratio of the mixed gas satisfies a range of Formula 1, where (Formula 1) (second hydrocarbon-based gas):(first hydrocarbon-based gas)=7:3 to 9:1.

16. The method for manufacturing the medical glass container according to claim 11, wherein the hydrocarbon-based gas that does not contain silicon is plasmatized by high frequency output or microwave output.

17. The method for manufacturing the medical glass container according to claim 11, comprising a process of forming an intermediate layer on a glass surface of the inner wall of the glass container by plasmatizing a silicon-containing gas inside a storage space of the glass container before forming the silicon-free diamond-like carbon film as the coat.

18. The method for manufacturing the medical glass container according to claim 11, comprising a hydrophilizing process for forming plasma by bringing a hydrocarbon-based gas or an oxygen gas modified with fluorine into contact with at least a part of an inner surface of the medical glass container before forming the coat and/or the intermediate layer.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0030] FIG. 1 is a cross-sectional view when a medical glass container according to the present embodiment is a vial.

[0031] FIG. 2 is a cross-sectional view when the medical glass container according to the present embodiment is an injector barrel.

[0032] FIG. 3 is a schematic diagram illustrating a high frequency type inner surface film formation apparatus for a vial.

[0033] FIG. 4 is a schematic diagram illustrating a microwave type inner surface film formation apparatus for a vial.

[0034] FIG. 5 is a schematic diagram illustrating a high frequency type inner surface film formation apparatus for an injector barrel.

[0035] FIG. 6 is a schematic diagram illustrating a microwave type inner surface film formation apparatus for an injector barrel.

DESCRIPTION OF EMBODIMENTS

[0036] While embodiments of the present invention will now be described in details, the present invention is not construed as being limited to such descriptions. Various modifications may be possible as long as the effects of the present invention are exhibited.

[0037] The medical glass container according to the present embodiment has a coat formed on at least a part of the inner wall of the glass container, wherein the coat is a silicon-free diamond-like carbon film.

(Glass Container)

[0038] The medical glass container includes a vial, an injector barrel, a syringe with needle, and a cartridge type syringe. Note that the injector barrel includes a syringe with needle and a cartridge type syringe. Glass forming the glass container includes borosilicate glass, aluminosilicate glass, or soda lime glass.

[0039] As illustrated in FIG. 1, when the medical glass container 1 is in the form of a vial, a coat 3 is formed on an inner wall 2a of the vial 2 at an area ratio of preferably 15% or higher, more preferably 30% or higher, and still more preferably 80% or higher. It is preferable that the coat 3 is formed on the entire bottom surface of the storage space of the vial. In addition, it is more preferable that the inner wall surface of the container lower than the center in height direction of the container 1 is formed on the entire surface. Furthermore, it is particularly preferable that the coat 3 is formed on the entire surface of the inner wall 2a of the glass container (vial 2). Peeling (delamination) of the silica component (SiO.sub.2 component) of the glass, which is abase material of the vial 2, does not easily occur due to presence of the coat 3. In particular, when the vial is formed of borosilicate glass, peeling of silica tends to easily occur. However, this peeling can be suppressed.

[0040] In addition, in the medical glass container 1 according to the present embodiment, the glass container is the vial 2 and further has a rubber stopper 4, and at least a part of the inner surface of the rubber stopper 4 is preferably coated with a diamond-like carbon film 6 or a fluororesin film. The rubber stopper 4 is formed of thermoplastic elastomer, butyl rubber (isobutyl/isoprene rubber), silicone rubber, or the like. Since the medicine contained in the vial 2 can be brought into contact with only the diamond-like carbon film or with only both the diamond-like carbon film and the fluororesin film without contact with glass or rubber, stability of the content is improved.

[0041] As illustrated in FIG. 2, when the medical glass container 20 is in the form of injector barrel (syringe), a coat 22 is preferably formed on a surface where at least the glass container (injector barrel 21) and a gasket 24 installed in a plunger 23 can be brought into contact by sliding. Due to the presence of the coat 22, it is possible to improve lubricity, that is, slidability of the plunger 23, so that the plunger 23 can be smoothly moved when it is pushed. Furthermore, the coat 22 is preferably formed on the entire surface of the inner wall 21a of the injector barrel 21. In addition to improvement of slidability, the coat 22 prevents contact between a medicinal liquid which is the content and glass which is a constituent material of the injector barrel 21, and due to the coat 22 having high water-repellent property, residual liquid is reduced.

[0042] In the present embodiment, the injector barrel 21 may be a prefilled syringe as well as a normal syringe. In addition, the shape of the tip of the injector barrel is not particularly limited, and various shapes such as a luer slip type, a luer lock type, a luer metal type, a catheter tip type, and an enema type may be employed.

[0043] As illustrated in FIG. 2, in the medical glass container according to the present embodiment, the medical glass container 20 is an injector barrel, and further includes the plunger 23 in which the gasket 24 is installed, and at least a part of the surface 24a of the gasket 24 is preferably coated with the diamond-like carbon film 25. The diamond-like carbon film 25 is preferably formed on a portion of the surface of the gasket 24 that comes into contact with the inner surface 21a of the injector barrel 21. The diamond-like carbon film 25 formed on the surface of the gasket 24 and the inner surface of the glass container 20 (surface of the coat 22) come into contact with each other, so that the plunger 23 can be moved more smoothly when it is pushed. In addition, the diamond-like carbon film 25 is preferably formed on a portion of the surface of the gasket 24 that comes into contact with the medicine. In addition to improvement of slidability of the plunger 23, it is possible to prevent contact between the gasket 24 and the medicine. Furthermore, more preferably, the diamond-like carbon film 25 is formed on both a portion of the surface of the gasket 24 that comes into contact with the inner surface of the injector barrel and a portion that comes into contact with the medicine. Note that the gasket 24 is formed of thermoplastic elastomer (such as butyl rubber or isoprene rubber), plastic (such as polypropylene or polystyrene), or the like.

[0044] A fluororesin film 26 may be arranged instead of the diamond-like carbon film 25 formed on the surface of the gasket 24 illustrated in FIG. 2. That is, in the medical glass container according to the present embodiment, it is preferable that the medical glass container 20 is an injector barrel, and further has the plunger 23 in which the gasket 24 is installed, and a fluororesin film 26 is bonded to at least a part of the surface 24a of the gasket 24 adjoining with the inner surface of the medical glass container 20 (the surface of the coat 22). It is possible to more smoothly move the plunger 23 when it is pushed. The fluororesin film may be formed of one or more fluororesins such as polytetrafluoroethylene, tetrafluoroethylene/perfluoroalkyl vinyl ether copolymer, tetrafluoroethylene/hexafluoropropylene copolymer, tetrafluoroethylene/ethylene copolymer, polyvinylidene fluoride, polychlorotrifluoroethylene, and chlorotrifluoroethylene/ethylene copolymer.

(Coat)

[0045] The coats 3 and 22 are silicon-free diamond-like carbon films. Here, the diamond-like carbon is also called a diamond-like carbon film, a DLC film, or an amorphous carbon film, and is a hydrogenated amorphous carbon film containing at least a carbon atom and a hydrogen atom. The coats 3 and 22 preferably have a thickness of 1 to 70 nm, and more preferably 2 to 10 nm. If the thickness is less than 1 nm, it may be difficult to form a uniform film without a defect. If the thickness exceeds 70 nm, peeling may occur, or coloring may exceed an allowable range.

[0046] Here, the coat 3 or 22 as a silicon-free diamond-like carbon film is a silicon-free and fluorine-containing diamond-like carbon film (hereinafter, referred to as F-DLC film in some cases) or a silicon-free and fluorine-free diamond-like carbon film (hereinafter, simply referred to as DLC film in some cases). Note that the fluorine-containing diamond-like carbon film is also called a fluorinated amorphous carbon film.

[0047] When the coat 3 or 22 is a silicon-free and fluorine-free diamond-like carbon film, the water-repellent property, the heat resistance, and the protein non-adsorption property are excellent.

[0048] When the coat 3 or 22 is a silicon-free and fluorine-containing diamond-like carbon film, the transparency, water-repellent property, the protein non-adsorption property, and the heat resistance are excellent. The fluorine content in the coat 3 or 22 is preferably 10 to 50 atomic % on the outermost surface of the coat. If the fluorine content is less than 10 atomic %, the act of the fluorine becomes less significant, and, for example, the water-repellent property and the transparency may decrease. If the fluorine content is more than 50 atomic %, the heat resistance may decrease. The fluorine content in the coat 3 or 22 is preferably in the range of 0 to 20 atomic % on the innermost surface of the coat in order to maintain adhesion. For this reason, the fluorine content preferably has a gradient composition that increases from the inner surface to the outermost surface of the coat.

[0049] According to the present embodiment, a silicon-containing intermediate layer is preferably provided between the glass surface of the inner wall and the coat of the glass container 2 or 21. By providing the silicon-containing intermediate layer, the adhesion of the film is improved. Specifically, there are (1) a mode in which a silicon-containing intermediate layer is formed on the glass surface of the inner wall of the glass container 2 or 21, and a silicon-free and fluorine-free diamond-like carbon film is further formed thereon, and (2) a mode in which a silicon-containing intermediate layer is formed on the glass surface of the inner wall of the glass container 2 or 21, and a silicon-free and fluorine-containing diamond-like carbon film is further formed thereon.

[0050] The mode in which the silicon-containing intermediate layer is formed on the glass surface of the inner wall of the glass container 2 or 21, and the silicon-free and fluorine-free diamond-like carbon film is further formed thereon will be described. It is preferable that the silicon-containing intermediate layer is, for example, a silicon oxide film, and the silicon oxide film contains silicon, oxygen, carbon, and hydrogen, and has a thickness of 3 to 50 nm. The thickness of the silicon oxide film is more preferably 5 to 20 nm. If the thickness of the silicon oxide film is smaller than 3 nm, the act of the intermediate layer becomes less significant, and the adhesion of the coat provided on the intermediate layer may decrease. If the thickness of the silicon oxide film is larger than 50 nm, a crack may be generated due to internal stress, or it may take time for film formation. In addition, the silicon-free and fluorine-free diamond-like carbon film provided on the intermediate layer preferably has a density of 1.6 to 2.4 g/cm.sup.3, a hydrogen content of 8 to 40 atomic %, and a thickness of 1 to 70 nm. Here, the density is more preferably 1.8 to 2.2 g/cm.sup.3, the hydrogen content is more preferably 10 to 30 atomic %, and the thickness is more preferably 2 to 10 nm. If the density is lower than 1.6 g/cm.sup.3, the heat resistance may decrease. If the density is higher than 2.4 g/cm.sup.3, a crack may be generated, or coloring may become severe. If the hydrogen content is less than 8 atomic %, the density may increase, which may cause cracking or severe coloring. If the hydrogen content is more than 40 atomic %, the density may decrease, and the heat resistance may decrease. If the thickness is smaller than 1 nm, it may be difficult to uniformly form the film, and a defect may be generated in the coat. If the thickness is larger than 70 nm, the transparency may decrease.

[0051] The mode in which the silicon-containing intermediate layer is formed on the glass surface of the inner wall of the glass container 2 or 21, and the silicon-free and fluorine-containing diamond-like carbon film is further formed thereon will be described. It is preferable that the silicon-containing intermediate layer is, for example, a silicon oxide film, and the silicon oxide film contains silicon, oxygen, carbon, and hydrogen, and may contain fluorine in some cases, and the thickness is 3 to 50 nm. The thickness of the silicon oxide film is more preferably 5 to 20 nm. If the thickness of the silicon oxide film is smaller than 3 nm, the act of the intermediate layer becomes less significant, so that the adhesion of the coat provided on the intermediate layer may decrease. If the thickness of the silicon oxide film is larger than 50 nm, a crack may be generated due to internal stress, or it may take time for film formation. In addition, it is preferable that the silicon-free and fluorine-containing diamond-like carbon film provided on the intermediate layer has a density of 1.6 to 2.4 g/cm.sup.3, a hydrogen content of 8 to 40 atomic %, an average fluorine content in the film of 10 to 20 atomic %, a fluorine content on the outermost surface of 8 to 50 atomic %, and a thickness of 1 to 70 nm. Here, more preferably, the density is 1.8 to 2.2 g/cm.sup.3, the hydrogen content is 10 to 30 atomic %, the fluorine content on the outermost surface is 10 to 40 atomic %, and the thickness is 2 to 10 nm. If the density is lower than 1.6 g/cm.sup.3, the heat resistance may decrease. If the hydrogen content is less than 8 atomic %, the density may increase, a crack may be generated, or coloring may become severe. If the hydrogen content is more than 40 atomic %, the density may decrease, and the heat resistance may decrease. If the fluorine content is less than 8 atomic %, the act of the fluorine becomes less significant, and, for example, the water-repellent property and the transparency may decrease. If the fluorine content is more than 50 atomic %, the heat resistance may decrease. If the thickness is smaller than 1 nm, uniformity of film formation may be degraded. If the thickness is larger than 70 nm, peeling may occur, or coloring may exceed an allowable range.

[0052] In the mode in which the silicon-containing intermediate layer is formed, and the silicon-free and fluorine-containing diamond-like carbon film is further formed thereon, the intermediate layer and the silicon-free and fluorine-containing diamond-like carbon film may have a gradient composition, so that they may form a substantially single-layered gradient composition film. Specifically, in the coats 3 and 22, (1) the outermost surface is a silicon-free and fluorine-containing diamond-like carbon surface, and the surface adjoining with the container inner surface is a silicon oxide surface or a fluorine-containing silicon oxide surface. (2) The gradient composition film has a density of 1.6 to 2.4 g/cm.sup.3 or preferably 1.8 to 2.2 g/cm.sup.3 from the outermost surface to a thickness of 1 nm. In addition, the hydrogen content from the outermost surface to the thickness of 1 nm is 8 to 40 atomic % or preferably 10 to 30 atomic %. In addition, the fluorine content from the outermost surface to the thickness of 1 nm is 8 to 50 atomic % or preferably 10 to 40 atomic %. (3) The surface of the silicon oxide adjoining with the inner surface of the container may contain silicon, oxygen, carbon, and hydrogen, and may contain fluorine. (4) The composition gradually changes in the thickness direction of the coat from the surface adjoining with the inner surface of the container to the outermost surface, and the thickness of the coat 3 or 22 as the gradient composition film is 1 to 70 nm or preferably 5 to 20 nm. If the density in the description (2) is less than 1.6 g/cm.sup.3 the heat resistance may decrease. If the density is higher than 2.4 g/cm.sup.3, a crack may occur, or coloring may become severe. If the hydrogen content is less than 8 atomic %, the density may decrease, and the heat resistance may decrease. If the hydrogen content is more than 40 atomic %, the density may increase, a crack may be generated, or coloring may become severe. If the fluorine content is less than 8 atomic %, the act of fluorine becomes less significant, and for example, the water-repellent property and the transparency may decrease. If the fluorine content is more than 50 atomic %, the heat resistance may decrease. If the thickness in the description (4) is smaller than 1 nm, uniformity of film formation may be degraded. If the thickness is larger than 70 nm, peeling may occur, or coloring may exceed an allowable range.

[0053] In the medical glass container according to the present embodiment, at least a part of the glass surface of the inner wall of the glass container 2 or 21 is preferably hydrophilized in the mode in which the intermediate layer is provided. By hydrophilizing the glass surface of the inner wall of the glass container 2 or 21, adhesion of the coat including the intermediate film is improved. In the hydrophilizing treatment, for example, a carbonyl group or a carboxyl group may be added to the glass surface, or an OH group may be added or bonded. When the medical glass container 1 or 20 is employed, a layer containing a carbonyl group with a thickness of 0.5 to 10 nm is preferably formed at the interface between the intermediate layer and the inner surface of the container, and more preferably, a layer containing a carbonyl group with a thickness of 1 to 5 nm is formed. In the hydrophilized form, the silicon-containing intermediate layer is, for example, a silicon oxide film, and the silicon oxide film contains silicon, oxygen, carbon, and hydrogen, and may contain fluorine. The film thickness is more preferably 3 to 50 nm. The thickness of the silicon oxide film is more preferably 5 to 20 nm. If the thickness of the silicon oxide film is smaller than 3 nm, the act of the intermediate layer becomes less significant, and adhesion of the coat provided on the intermediate layer may decrease. If the thickness of the silicon oxide film is larger than 50 nm, a crack may be generated due to internal stress, and it may take time for film formation.

[0054] The diamond-like carbon film 6 formed on the surface of the rubber stopper 4 and the diamond-like carbon film 25 formed on the surface of the gasket 24 preferably contain hydrogen of 30 to 45 atomic % and fluorine of 0 to 20 atomic %, and has a thickness of preferably 1 to 70 nm or more preferably 5 to 20 nm.

[0055] The fluororesin film that coats the surface of the rubber stopper 4 may be formed of one or more fluororesins such as polytetrafluoroethylene, tetrafluoroethylene/perfluoroalkyl vinyl ether copolymer, tetrafluoroethylene/hexafluoropropylene copolymer, tetrafluoroethylene/ethylene copolymer, polyvinylidene fluoride, polychlorotrifluoroethylene, or chlorotrifluoroethylene/ethylene copolymer.

[0056] The medical glass container 1 or 20 preferably has a light-transmitting property. Specifically, the transmittance at a wavelength of 590 to 610 nm or 290 to 450 nm is preferably 45% or higher, or more preferably 60% or higher. An evaluation method for a transparency test is based on Japanese Pharmacopoeia (17th Edition), 7. Tests for Containers and Packing Materials, 7.01 Test for Glass Containers for Injections, (5) Light transmission test for light-resistant containers.

(Apparatus for Manufacturing Medical Glass Container)

[0057] Next, before explaining the method for manufacturing the medical glass container, a manufacturing apparatus will be described. FIG. 3 is a schematic diagram illustrating a high frequency type inner surface film formation apparatus for a vial. The high frequency type inner surface film formation apparatus 104 for a vial illustrated in FIG. 3 has source gas inlet lines 31, 32, and 33. Each source gas inlet line has a stop valve 34 and a gas flowmeter 35, and is connected to a single mixed-gas pipe 36. Although FIG. 3 illustrates a configuration in which three source gas inlet lines are provided, more source gas inlet lines may also be provided. The pipe 36 is connected to a conductive pipe 43a which also serves as an internal electrode and a gas introduction pipe arranged in a vacuum chamber 38. The vacuum chamber 38 is grounded, and a vacuum gauge 37 is connected thereto. In addition, inside the vacuum chamber 38, a vial 2, an external electrode 45 arranged to surround a side surface and a bottom surface of the vial 2, a dielectric member 46 arranged to surround the external electrode 45, and an outer casing 48 that surrounds the dielectric member 46 and is formed of a conductive material for stabilizing plasma of the source gas are arranged. The vacuum chamber 38 is connected to a degassing pipe 49. In addition, the external electrode 45 is connected to an automatic matching device 40 so as not to be electrically connected to the vacuum chamber 38. The automatic matching device 40 is connected to a high frequency power supply 41. The high frequency is set to, for example, 1 to 100 MHz, or preferably 13.56 MHz. The source gas discharged from the conductive pipe 43a flows through the inside of the vial 2, is discharged from the tip opening thereof passes through the space 48a provided in the upper side of the outer casing 48, and then reaches the internal space of the vacuum chamber 38. Then, the gas is discharged through the degassing pipe 49.

[0058] FIG. 4 is a schematic diagram illustrating a microwave type inner surface film formation apparatus for a vial. The microwave type inner surface film formation apparatus 200 for a vial illustrated in FIG. 4 has source gas inlet lines 31, 32, and 33. Each source gas inlet line has a stop valve 34 and a gas flowmeter 35, and is connected to a single mixed-gas pipe 36. Although FIG. 4 illustrates a configuration in which three source gas inlet lines are provided, more source gas inlet lines may also be provided. The pipe 36 is connected to a gas introduction pipe 43b arranged in the microwave shield 39. A vacuum gauge 37 is connected to the pipe 36. In addition, inside the microwave shield 39, a vial 2, a dielectric member 46 for fixing an opening of the vial 2 to prevent gas leakage, a pedestal 52 formed of a dielectric material for loading the vial 2, a vacuum room 51, and a degassing pipe 50 connected to the vacuum room 51 are arranged. The opening of the vial 2 is connected to the space inside the vacuum room 51. When the inside of the vacuum room 51 is evacuated, the internal space of the vial 2 is also evacuated. In addition, a microwave oscillator 42 for outputting a microwave is provided inside the microwave shield 39. The microwave frequency is, for example, 0.9 to 45 GHz, or preferably 2.45 GHz. The source gas discharged from the tip opening of the gas introduction pipe 43b flows through the inside of the vial 2, is discharged from its opening, passes through the inside of the vacuum room 51, and is then discharged through the degassing pipe 49.

[0059] FIG. 5 is a schematic diagram illustrating a high frequency type inner surface film formation apparatus for an injector barrel. The high frequency type inner surface film formation apparatus 300 for an injector barrel illustrated in FIG. 5 has source gas inlet lines 31, 32, and 33. Each source gas inlet line has a stop valve 34 and a gas flowmeter 35, and is connected to a single mixed-gas pipe 36. Although FIG. 5 illustrates a configuration in which three source gas inlet lines are provided, more source gas inlet lines may also be provided. The pipe 36 is connected to a gas introduction pipe 43c arranged inside a vacuum chamber 38. The vacuum chamber 38 is grounded, and a vacuum gauge 37 is connected thereto. In addition, inside the vacuum chamber 38, an injector barrel 21, an external electrode 45 arranged to surround the injector barrel 21, a dielectric member 46 arranged to surround the external electrode 45, and an outer casing 48 arranged to surround the dielectric member 46 and formed of a conductive material for stabilizing plasma of the source gas are arranged. The vacuum chamber 38 is connected to the degassing pipe 49. In addition, the external electrode 45 is connected to an automatic matching device 40 so as not to be electrically connected to the vacuum chamber 38. The automatic matching device 40 is connected to a high frequency power supply 41. The frequency of the high frequency wave is, for example, 1 to 100 MHz, or preferably 13.56 MHz. A tip portion of the gas introduction pipe 43c is connected to a coupling portion which is the tip portion of the injector barrel 21. The source gas is delivered from the tip opening of the gas introducing pipe 43c to the coupling portion which is the tip portion of the injector barrel 21, flows inside the injector barrel 21, is discharged from the opening in the flange side of the injector barrel 21, passes through the space 48a provided in the tipper side of the outer casing 48, and then reaches the internal space of the vacuum chamber 38. Then, the gas is discharged through the degassing pipe 49.

[0060] FIG. 6 is a schematic diagram illustrating a microwave type inner surface film formation apparatus for an injector barrel. The microwave type inner surface film formation apparatus 400 for an injector barrel illustrated in FIG. 6 has source gas inlet lines 31, 32, and 33. Each source gas inlet line has a stop valve 34 and a gas flowmeter 35, and is connected to a single mixed-gas pipe 36. Although FIG. 6 illustrates a configuration in which three source gas inlet lines are provided, inure source gas inlet lines may also be provided. The pipe 36 is connected to a gas introduction pipe 43b arranged in the microwave shield 39. A vacuum gauge 37 is connected to the pipe 36. In addition, inside the microwave shield 39, an injector barrel 21, a dielectric member 46 for fixing a coupling portion (opening) of the tip portion of the injector barrel 21, a pedestal 52 formed of a dielectric material for loading a flange side of the injector barrel 21, and a degassing pipe 50 connected to the opening of the flange side of the injector barrel 21 are arranged. The coupling portion (opening) of the tip portion of the injector barrel 21 and the tip opening of the gas introduction pipe 43b are connected so as to prevent leakage. The opening of the flange side of the injector barrel 21 is connected to the degassing pipe 50. In addition, a microwave oscillator 42 for outputting a microwave is provided inside the microwave shield 39. The microwave frequency is, for example, 0.9 to 45 GHz, or preferably 2.45 GHz. The source gas introduced from the tip opening of the gas introduction pipe 43b flows through the inside of the injector barrel 21, is discharged from the opening of the flange side, and is then discharged through the degassing pipe 49.

(Method for Manufacturing Medical Glass Container)

[0061] A method for manufacturing a medical glass container according to the present embodiment is a method for manufacturing a medical glass container 1 or 20 having a coat 3 formed on at least a part of an inner wall of the medical glass container, the method including a process of forming a silicon-free diamond-like carbon film as the coat 3 by plasmatizing a silicon-free hydrocarbon-based gas as a constituent element inside a glass container, specifically inside a storage space of the vial 2 or the injector barrel 21.

[0062] Here, the silicon-free hydrocarbon-based gas includes a first hydrocarbon-based gas that does not contain fluorine or silicon as a constituent element (hereinafter, also referred to as first hydrocarbon-based gas in some cases), and a second hydrocarbon-based gas that is modified with fluorine and does not contain silicon as a constituent element (hereinafter, also referred to as second hydrocarbon-based gas in some cases).

[0063] The first hydrocarbon-based gas includes, for example, acetylene, methane, ethylene, or propane, and acetylene or methane is preferable.

[0064] The second hydrocarbon-based gas includes, for example, hexafluoroethane. C.sub.6F.sub.10(CF.sub.3).sub.2, and C.sub.6F.sub.6, and hexafluoroethane is preferable.

[0065] In order to plasmatize the silicon-free hydrocarbon-based gas, for example, plasmatization is performed by applying a high frequency wave or a microwave using the film formation apparatuses illustrated in FIGS. 3 to 6.

[0066] According to the present embodiment, it is preferable that the silicon-free hydrocarbon-based gas is a mixed gas of the first hydrocarbon-based gas that does not contain fluorine or silicon as a constituent element and the second hydrocarbon-based gas that is modified with fluorine and does not contain silicon as a constituent element, and the coat is a silicon-free and fluorine-containing diamond-like carbon film. By using the aforementioned mixed gas, the fluorine content in the coat can be easily set to a desired ratio. The gas volume ratio of the nixed gas preferably satisfies a range of Formula 1. The fluorine content in the coat is within a predetermined range, for example, 8 to 50 atomic % (atomic percentage), and an excellent water repellency effect is obtained.

(second hydrocarbon-based gas):(first hydrocarbon-based gas)=7:3 to 9:1(Formula 1)

[0067] According to the present embodiment, it is preferable that the silicon-free hydrocarbon-based gas is the first hydrocarbon-based gas that does not contain fluorine or silicon as a constituent element, and the coat is a silicon-free and fluorine-free diamond-like carbon film. It is possible to easily form the silicon-free and fluorine-free diamond-like carbon film.

[0068] According to the present embodiment, it is preferable that, before forming the silicon-free diamond-like carbon film as a coat, a process of forming the intermediate layer on the glass surface of the inner wall of the vial 2 or the injector barrel 21 by plasmatizing the silicon-containing gas inside the storage space of the vial 2 or the injector barrel 21 is provided. By providing the silicon-containing intermediate layer, adhesion of the coat and uniformity of the coat are improved, and the inner surface temperature at the time of the hydrophilizing treatment increases, so that there is an effect of improving the density of the coat.

[0069] The silicon-containing gas includes, for example, a mixed gas containing an oxygen gas and trimethylsilane (TrMS), hexamethyldisiloxane (HMDSO), tetramethylorthosilicate (Si(OCH.sub.3).sub.4), or tetraethoxysilane (Si(OC.sub.2H.sub.5).sub.4).

[0070] According to the present embodiment, when forming the coat, the mixing ratio between the silicon-containing gas and the silicon-free hydrocarbon-based gas may be set to 100:0 at the beginning of film formation, may be changed as the film formation time progresses, and may beset to 0:100 at the end of film formation. In this case, the coat becomes a gradient composition film.

[0071] According to the present embodiment, it is preferable that, before forming the coat and/or the intermediate layer, a hydrophilizing process for forming plasma by bring a hydrocarbon-based gas or an oxygen gas modified with fluorine into contact with at least a part of the inner surface of the vial 2 or the injector barrel 21 is provided. Since the glass surface of the inner wall of the vial 2 or the injector barrel 21 is hydrophilized, adhesion of the coat and uniformity of the coat are improved, and the inner surface temperature at the time of the hydrophilizing treatment increases, so that there is an effect of increasing the density of the coat. The hydrocarbon-based gas modified with fluorine includes hexafluoroethane, C.sub.6F.sub.10(CF.sub.3).sub.2, and C.sub.6F.sub.6, and hexafluoroethane is preferable.

EXAMPLES

[0072] Hereinafter, the present invention will be described in more details with reference to examples, but the present invention is not construed as being limited to the examples.

[0073] Conditions for forming a film on a flat plate are as follows.

[0074] Equipment: Parallel plate low-pressure plasma CVD apparatus

[0075] High frequency output: 200 W, 13.56 MHz

[0076] Initial decompremssion: 0.02 torr

[0077] Film formation pressure: 0.1 torr

[0078] Film formation time: As shown in the following table

[0079] Mixed gas: As shown in the following table, where ratios indicate volume/flow-rate mixing ratio.

[0080] Pretreatment: None or O.sub.2 plasma treatment for 5 min or C.sub.2F.sub.6 plasma treatment for 5 min Base material: Borosilicate glass substrate (having a length of 20 mm, a width of 20 mm, and a thickness of 0.1 mm) (denoted as glass in the table) or Si substrate (having a length of 20 mm, a width of 20 mm, and a thickness of 0.38 mm) (denoted as Si in the table))

[0081] The evaluation was performed as follows.

[0082] Thickness: Step type thickness gauge (produced by DEKTAK XT, BRUKER)

[0083] Contact angle: The contact angle measurement device (DM300, produced by KYOWA) and pure water as an alternative to the aqueous content to be contacted were used. The measurement was performed by conforming to JIS R3257 Testing method of wettability of glass substrate. Note that the aqueous content is a liquid chemical.

[0084] Adhesion: Cross-cut test, JIS K 5600-5-6 (1999)

[0085] The conditions for performing film formation on the inner surface of the container are as follows.

[0086] Equipment: Low pressure plasma CVD apparatus shown in FIG. 3 or 5

[0087] High frequency output: 100 W, 13.56 MHz

[0088] Initial decompression: 0.02 torr

[0089] Pressure for film formation: 2 torr

[0090] Film formation time: As shown in the following table

[0091] Mixed gas: As shown in the following table, where the ratios indicate volume/flow-rate mixing ratios

[0092] Pretreatment: None, O.sub.2 plasma treatment for 5 min or C.sub.2F.sub.6 plasma treatment fir 5 min.

[0093] Base material: Borosilicate glass vial (having an outer diameter of 16 mm, an inner diameter of 14 mm, a height of 35 mm, and a volume of 2 ml) (in the table, referred to as bottle, and hereinafter, also referred to as vial in some cases), or an injector barrel (having an outer diameter of 12.3 mm, an inner diameter of 10.6 mm, a length of 60 mm, and a volume of 2 ml) (in the table, referred to as injector barrel)

Example A

[0094] An F-DLC film (hereinafter, referred to as F-DLC in the table) was deposited as a coat of the outermost layer. No intermediate layer was provided. The results are shown in Tables 1, 2, and 3.

TABLE-US-00001 TABLE 1 Film formation Measured Contact Outermost time thickness angle Substrate layer Pretreatment Gas (sec.) (nm) () Example A 1 glass F-DLC none C.sub.2H.sub.2C.sub.2F.sub.6 (2:8) 20 56.8 96.7 2 Si F-DLC none C.sub.2H.sub.2C.sub.2F.sub.6 (2:8) 20 59.1 96.3 3 glass F-DLC none C.sub.2H.sub.2C.sub.2F.sub.6(6:4) 6.25 14.6 77.1 4 glass F-DLC none C.sub.2H.sub.2C.sub.2F.sub.6(6:4) 20 49.8 77.6 5 glass F-DLC none C.sub.2H.sub.2C.sub.2F.sub.6(4:6) 6.25 16.4 80.1 Comparative Example A 1 glass glass 0 30.5 2 Si Si 0 55.0 3 glass F-DLC none C.sub.2H.sub.2C.sub.2F.sub.6(0:10) 20 0 17.8

TABLE-US-00002 TABLE 3 Film formation Measured Contact Comparative Outermost time thickness angle Example A Substrate layer Pretreatment Gas (sec.) (nm) () 1 glass SiO:CH none TrMSO.sub.2(6:4) 20 28.9 85.7

Example B

[0095] A DLC film (hereinafter, referred to as DLC in the table) was formed as a coat of the outermost layer. No intermediate layer was provided. The results are shown in Table 4.

TABLE-US-00003 TABLE 4 Film formation Measured Contact Outermost time thickness angle Example B Substrate layer Pretreatment Gas (sec.) (nm) () 1 glass DLC none C.sub.2H.sub.2 2 3.8 80.8 2 glass DLC none C.sub.2H.sub.2 5 9.5 80.5

Example C

[0096] A DLC film was formed as a coat of the outermost layer. A silicon-containing intermediate layer (SiO:CH) was formed as the intermediate layer. The results are shown in Table 5.

TABLE-US-00004 TABLE 5 Film formation Measured Gas time (sec) thickness (nm) Contact Outermost (for outermost/for (outermost/ (outermost/ angle Example C Substrate layer Pretreatment intermediate layer) intermediate layer) intermediate layer) () 1 glass DLC none C.sub.2H.sub.2/TrMSO.sub.2(6:4) 2/3 3.8/4.3 81.1 2 glass DLC none C.sub.2H.sub.2/TrMSO.sub.2(6:4) 2/7 4.1/10.2 80.6 3 glass DLC none C.sub.2H.sub.2/TrMSO.sub.2(6:4) 2/10 3.7/14.8 82.6

Example D

[0097] A DLC film or an F-DLC film was formed as a coat of the outermost layer. In Examples D-4 to D-6, a silicon-containing intermediate layer (SiO:CH) was formed as the intermediate layer. The results are shown in Table 6.

TABLE-US-00005 TABLE 6 Gas Film formation Measured (uppermost time (sec) thickness (nm) layer) or (uppermost layer) (uppermost layer) Contact Outermost (for outermost/for or (for outermost/for or (for outermost/for angle Example D Substrate layer Pretreatment intermediate layer) intermediate layer) intermediate layer) () 1 glass DLC none C.sub.2H.sub.2 2 4.1 70.9 2 glass DLC O.sub.2 C.sub.2H.sub.2 2 3.9 70.6 3 glass DLC C.sub.2F.sub.6 C.sub.2H.sub.2 2 4.0 81.6 4 glass DLC none C.sub.2H.sub.2/TrMSO.sub.2 (6:4) 2/2 3.8/3.1 77.4 5 glass DLC O.sub.2 C.sub.2H.sub.2/TrMSO.sub.2 (6:4) 2/2 4.0/2.9 70.9 6 glass DLC C.sub.2F.sub.6 C.sub.2H.sub.2/TrMSO.sub.2 (6:4) 2/2 3.8/2.8 77.1

Example E

[0098] A DLC film or an F-DLC film was formed as a coat of the outermost layer for Examples E-1 and E-2. In Comparative example E-1, a glass substrate having no coat in the outermost layer was employed.

[Transmittance]

[0099] The measurement was performed in accordance with JP17, 7.01 Test for Glass Containers for Injections, (5) Light transmission test for light-resistant container. Specifically, it was performed as follows. Absorption at a wavelength of 290 to 810 nm was measured using an ultraviolet/visible spectrophotometer (ASUV6300PC, produced by AS ONE corporation).

[0100] The measurement results for the contact angle and the transmittance are shown in Tables 7 and 8. In Tables 7 and 8, the transmittances at wavelengths of 290 nm, 450 nm, 590 nm, and 610 nm were compared.

TABLE-US-00006 TABLE 7 film Transmittance Gas formation Measured Contact (%) Outermost (uppermost time thickness angle 290 nm/450 nm Example E Substrate layer Pretreatment layer) (sec.) (nm) () 590 nm/610 nm 1 glass DLC none CH.sub.4 40 10.5 83.8 44.28/87.52/ 91.33/91.59 2 glass F-DLC none CH.sub.4/C.sub.2F.sub.6(2:8) 40 26.2 97.0 46.17/92.13/ 93.15/93.17

TABLE-US-00007 TABLE 8 Film Transmittance Gas formation Measured Contact (%) Comparative Outermost (uppermost time thickness angle 290 nm/450 nm Example E Substrate layer Pretreatment layer) (sec.) (nm) () 590 nm/610 nm 1 glass 0 32.0 52.50/92.45/ 93.30/93.32

Example F

[0101] A DLC film equivalent to that of Example E-1 or an F-DLC film equivalent to that of Example E-2 was formed on the inner wall of the medical glass container (vial having an outer diameter of 23 mm, an inner diameter of 21 mm, a height of 35 mm, and a volume of 5 nil, hereafter referred to as vial 2) as a coat of the outermost layer in Examples F-1 and F-2. In Comparative example F-1, a medical glass container (vial 2) having no coat on the outermost layer was prepared.

[Remaining Amount of Water]

[0102] The remaining amount of water was measured as follows. Masses of the vial 2, the rubber stopper, and the aluminum cap were measured (mass 1). Then, the vial 2 is filled with ultra pure water at about 50% of the full volume, the rubber stopper and the aluminum cap were covered with lids, and then the mass was measured (mass 2). Then, the syringe was pieced into the rubber stopper, and the vial was sucked up while being turned upside down and was then weighed (mass 3). Each mass was measured using an electronic balance (MSA224S100DI, produced by SARTORIUS). The remaining amount of water was obtained by subtracting the mass 1 from the mass 3.

[Absorption Amount of Serum Albumin]

[0103] First, the coated vial 2 was washed with ultra pure water and was dried at the room temperature. Then, a BSA (bovine serum albumin) solution of 10 ug/mL was transferred to each dried vial 2 by 1 mL, the vial 2 was moved to come into contact with the whole solution, and the solution was left at rest for 10 minutes. Then, the BSA solution in each vial 2 was taken by 10 ug, the fluorescence at a wavelength of 470/570 nm was measured, and the adsorption amount was calculated from the calibration curve. For the measurement of fluorescence, a plate reader (EnSpire, produced by Perkin Elmer, Inc.) was used.

[0104] Tables 9 and 10 show the measurement results for the remaining amount of water and the absorption amount of serum albumin.

TABLE-US-00008 TABLE 9 Remaining Absorption amount Outermost amount of of serum Example F layer water (g) albumin (ug/vial) 1 DLC 0.009 3.65 2 F-DLC 0.004

TABLE-US-00009 TABLE 10 Remaining Absorption amount Comparative Outermost amount of of serum example F layer water (g) albumin (ug/vial) 1 0.092 5.20

Example G

[0105] A DLC film equivalent to that of Example E-1 was formed on the inner wall of the medical glass container (vial 2) as a coat of the outermost layer in Example G-1. In Comparative example G, a medical glass container (vial 2) having no coat of the outermost layer was employed.

[Elution Amount after Steam Sterilization]

[0106] Measurement was performed in accordance with EP 8.4, 3.2.1. Glass containers for pharmaceutical use test A. hydrolytic resistance of the inner surface of glass containers (surface test). Specifically, the measurement was performed as follows. Each vial 2 was filled with various solutions by 90% of the full volume to obtain an extract liquid subjected to the high-pressure stream sterilization at a temperature of 121 C. for one hour. Then, a metal ion concentration of the extract liquid was measured using an ICP emission spectrometer (OPTIMA 8300, produced by PerkinElmer, Inc.).

[Number of Insoluble Particulate Matter Contained Per 1 mL after Steam Sterilization]

[0107] The measurement was performed in accordance with JP17, 6.07 Insoluble Particulate Matter Test for Injections, 1. Method 1. Light Obscuration Particle Count Test. Specifically, it was performed as follows. Each vial 2 was filled with various solutions by 90% of the full volume to obtain an extract liquid after the high-pressure steam sterilization at a temperature of 121 C. for one hour. Then, the number of insoluble particulate matter in the extract liquid was measured using an in-liquid particle counter (KL-04, produced by RION Co., Ltd.).

[0108] Tables 11 and 12 show the measurement results of the elution amount after steam sterilization and the number of insoluble particulate matter contained per 1 mL after steam sterilization

TABLE-US-00010 TABLE 11 Number of insoluble particulate matter contained Elution amount after steam per 1 mL after steam sterilization (number) sterilization (mg/L) Si/Na 1.5 .Math. 2 m/2 .Math. 3 m/10 .Math. 25 m KCl aqueous KCl aqueous solution of Phthalic acid solution of Phthalic acid 0.9 wt % buffer solution 0.9 wt % buffer solution Example G Water (pH = 8) (pH = 4.01) Water (pH = 8) (pH = 4.01) 1 0.164/0.031 0.214/1.999 0.165/0.63 13.5/4/0 12.5/5/1 32/8/0

TABLE-US-00011 TABLE 12 Number of insoluble particulate matter contained Elution amount after steam per 1 mL after steam sterilization (number) sterilization (mg/L) Si/Na 1.5 .Math. 2 m/2 .Math. 3 m/10 .Math. 25 m KCl aqueous KCl aqueous solution of Phthalic acid solution of Phthalic acid Comparative 0.9 wt % buffer solution 0.9 wt % buffer solution Example G Water (pH = 8) (pH = 4.01) Water (pH = 8) (pH = 4.01) 1 0.186/0.193 1.046/7.816 0.180/1.041 63.5/23/1 189/59.5/1.5 73.5/21.5/3.5

[0109] As shown in Tables 7 and 8, from comparison between Examples E-1 and E-2 and Comparative Example E-1, it is possible to increase the contact angle with the aqueous content by forming the diamond-like carbon film on the glass substrate. Furthermore, from comparison between Examples E-1 and E-2, it is possible to improve the transmittance of the glass substrate by incorporating a high content of fluorine into the diamond-like carbon film.

[0110] As shown in Tables 9 and 10, from comparison between Examples F-1 and F-2 and Comparative example F-1, it is possible to reduce the amount remaining in the container and suppress aggregation (absorption) of protein by forming the diamond-like carbon film on the inner wall of the medical glass container (vial). In addition, from comparison between Examples F-1 and F-2, it is possible to minimize the amount remaining in the container by incorporating a high content of fluorine into the diamond-like carbon film.

[0111] As shown in Tables 11 and 12, by forming a diamond-like carbon film corresponding to that of Example E-1 on the inner wall of a medical glass container (vial), it is possible to reduce the elution amount of metal ions (Si ions, Na ions) to the aqueous content and the amount of insoluble particulate matter and improve stability of the aqueous content.

DESCRIPTION OF REFERENCE SIGNS

[0112] 1, 20 medical glass container [0113] 2 glass container (vial as film formation target) [0114] 2a inner wall of vial [0115] h height direction of container [0116] 3, 22 coat [0117] 4 rubber stopper [0118] 6, 25 diamond-like carbon film [0119] 21 glass container (injector barrel as film formation target) [0120] 21a inner wall of injector barrel [0121] 23 plunger [0122] 24 gasket [0123] 24a surface of gasket [0124] 26 fluororesin film [0125] 31, 32, 33 source gas inlet line [0126] 34 stop valve [0127] 35 gas flowmeter [0128] 36 pipe [0129] 37 vacuum gauge [0130] 38 vacuum chamber [0131] 39 microwave shield [0132] 40 automatic matching device [0133] 41 high frequency power supply [0134] 42 microwave oscillator [0135] 43a conductive pipe [0136] 43b gas introduction pipe [0137] 43c gas introduction pipe [0138] 45 external electrode [0139] 46 dielectric member [0140] 48 outer casing [0141] 48a space [0142] 49 degassing pipe [0143] 50 degassing pipe [0144] 51 vacuum room [0145] 52 pedestal [0146] 100 high frequency type inner surface film formation apparatus for vial [0147] 200 microwave type inner surface film formation apparatus for vial [0148] 300 high frequency type inner surface film formation apparatus for injector barrel [0149] 400 microwave type inner surface film formation apparatus for injector barrel.