JPH08266594A - Method for sterilizing vial - Google Patents

Abstract

PURPOSE: To provide a method for sterilizing vials for medicines which makes it possible to sterilize vial surfaces and to sterilize the slight spaces between rubber plugs and caps in a process for producing the medicine vials and obviates the occurrence of the deterioration of the medicine vials. CONSTITUTION: This method sterilizing the vials 1 comprises hermetically closing the aperture of the vial 1 in which medicines are housed via the rubber plug 3 and the metallic cap 2 covering the front surface thereof, then irradiating the metallic cap 2 with a low energy electron beam from its outer surface. The cap 2 is constituted by selecting its thickness at about the thickness at which the electron beam transmits the thickness of the cap 2 and does not pass the rubber plug 3.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an improvement in a method of sterilizing a vial as a medical instrument.

[0002]

2. Description of the Related Art Conventionally, a drug or the like sealed in a vial is filled with the drug in an aseptic state in a vial, and then a rubber stopper is applied to cover the aluminum cap as a metal cap, and a rubber is squeezed by a caulking machine. The stopper and cap are caulked together and shipped as the final product. However, in recent years, sterilization or sterilization of the surface of the vial bottle and sterilization or sterilization of a slight gap between the rubber stopper and the aluminum cap have been required in the final step of the series of steps for manufacturing the drug vials.

[0003]

Generally, EOG gas, heat, gamma rays, or high-energy electron beams are used for sterilization of medical instruments. However, E
The sterilization with OG gas may cause the gas to enter the inside of the vial via a slight gap of the rubber stopper, which leads to deterioration of the drug. Further, even if there is no inflow into the interior, there remains a problem that the drug remains on the surface portion. Heat sterilization leads to alteration of the drug. Moreover, although surface sterilization is possible with ultraviolet ray sterilization, sterilization of gaps is not possible at all. Further, sterilization with gamma rays or high-energy electron beams has a large penetrating power, and the medicine inside is also irradiated through the bottle, which causes the deterioration of the medicine. Moreover, since the energy is large, a simple self-shielding device cannot be used for shielding X-rays generated after irradiation of the object, and a dedicated building shielded with concrete or the like is required, and the device becomes large and expensive, There are problems such as inlining.

As described above, in order to carry out a sterilization treatment of a higher grade instead of the sterilization treatment of medical instruments, the above-mentioned means are more restricted, the sterilization by EOG gas and heat is insufficient, and gamma rays or Electron beam sterilization is required. The present invention has been made in view of the above, and at the final stage of the drug vial manufacturing process, sterilization of the surface of the vial bottle in which the drug is sealed and sterilization of a slight gap between the rubber stopper and the metal cap coated on the upper surface thereof. Enable
Moreover, it is an object of the present invention to provide a method for sterilizing a vial bottle that does not cause deterioration of a drug vial.

[0005]

To achieve the above object, the present invention seals the opening of a vial containing a drug via a rubber stopper and a metal cap covering the upper surface of the vial, and further, the outer surface of the cap. In the method for sterilizing a vial irradiating with a low energy electron beam, the thickness of the cap of the vial is selected so that the electron beam penetrates and the rubber stopper does not pass through. The wall thickness of the metal cap is 150 to 600 g / m in terms of surface density.
Stipulate in ² . Further, the acceleration voltage of the low energy electron beam is set to 300 kV or less.

[0006]

With the above construction, the gap between the surface of the vial and the upper surface of the rubber stopper and the cap can be completely sterilized without affecting the drug contained in the vial. Moreover, the thickness of the metal cap is 150 to 150 in terms of areal density.
It is preferably 600 g / m ² . From the relationship diagram between electron beam dose and penetration depth, the area density is 150g / m
^If it is ² or less, the mechanical strength is insufficient and 600 g / m ²
This is because if it is above, the penetrating power is insufficient for the low energy electron beam of 300 kV or less. Further, by using an electron beam accelerating voltage of 300 kV or less, a self-shielding structure is possible, and a compact low-energy electron beam irradiation apparatus can be used for easy in-line construction.

[0007]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS An embodiment of the present invention will be described below with reference to the drawings. First, the electron beam irradiation apparatus used in the method of this embodiment will be described. This electron beam irradiation device is a product name Electro Curtain (registered trademark) CB200 / 45/300 manufactured by Energy Science Co., Ltd., and as shown in FIG. 1, an electron beam generation unit 10, an irradiation chamber 20, and an irradiation window unit 30.
And with. The electron beam generator 10 includes a terminal 12 that generates an electron beam and an accelerating tube 14 that accelerates the electron beam generated at the terminal 12 in a vacuum space (acceleration space). In addition, the inside of the electron beam generator 10 is
In order to prevent electrons from colliding with gas molecules and losing energy, they are kept at a high vacuum of 10 ⁻⁴ to 10 ⁻⁵ Pascal by a diffusion pump or the like not shown. Terminal 12
It has a linear filament 12a that emits thermoelectrons, a gun structure 12b that supports the filament 12a, and a grid 12c that controls thermoelectrons generated in the filament 12a. The irradiation chamber 20 includes an irradiation space 22 for irradiating the object to be processed with an electron beam. The object to be processed is moved from the left side to the right side in FIG. 1 by a conveying means (not shown) such as a conveyor in the irradiation chamber 20. Moving. The periphery of the electron beam generator 10 and the irradiation chamber 20 is covered with lead in order to prevent X-rays that are secondarily generated during electron beam irradiation from leaking to the outside. The irradiation window section 30 has a window foil 32 made of a metal foil and a window frame structure 34 that cools the window foil 32 and supports the window foil. The window foil separates the vacuum atmosphere in the electron beam generating unit 10 from the irradiation atmosphere in the irradiation chamber 20, and takes out the electron beam into the irradiation chamber through the window foil. In this window foil 32,
Usually, titanium foil is used.

When a current is applied to the filament 12a to heat it, the filament emits thermoelectrons, and the electron beam is attracted in all directions by a control voltage applied between the filament 12a and the grid 12c. Of these, only those that have passed through the grid 12c can be effectively taken out as electron beams. Further, the electron beam extracted from the grid 12c is accelerated in the acceleration space in the accelerating tube 14 by the acceleration voltage applied between the grid and the window foil 32, then penetrates the window foil 32, and the irradiation window portion The object to be processed conveyed in the irradiation chamber 20 below 30 is irradiated.

Next, a method of sterilizing a vial according to the present invention will be described. The vial used in this example is shown in FIG. Reference numeral 1 is a glass vial having a wall thickness of 20 microns. 2 is an aluminum cap with a wall thickness of 250
Micron, 3 is a butyl rubber stopper and has a wall thickness of 3 mm. Then, assuming that the specific gravity of the glass is 2.2, the specific gravity of the aluminum cap is 2.7, and the specific gravity of butyl rubber is 1, the electron beam transmittance in the case where the electron beam irradiation device is irradiated with an electron beam at an acceleration voltage of 250 kV is illustrated. 3 shows. As is clear from the figure, 2
Aluminum having a penetration depth of 10% at an accelerating voltage of 50 kV has a thickness of 185 μm, and is preferably less than this.

Further, the dose of the vial was measured. As the dosimeter, RCD (Radiachromic Dosimeter) was used. Dose measurement parts are shown in A, B and C of FIG. The acceleration voltage of the electron beam was 250 KV. Table 1 shows the results.

[0011]

[Table 1]

Generally, the thickness of the aluminum cap of commercially available vials is 250 μm or more, and no electron beam reaches the surface B of the butyl rubber stopper with this thickness. On the other hand, at 150 μm, about 45% of the aluminum surface A reaches the surface B of the butyl rubber plug. Further, no electron beam penetrates the inside of the vial, and there is no fear of affecting the drug as the content.
This agrees with the curve of the electron beam dose-penetration depth characteristic diagram of FIG.

Then, a sterilization test was actually conducted. The dosimetry was performed by RCD (Radiachromic Dosimeter), and the measurement site was measured at the position A in FIG. The indicator bacterium is Bacillus pumil
us E601 (spores), electron beam acceleration voltage was 250 kV. The indicator bacterium was smeared on the upper surface of the butyl rubber stopper. The results are shown in FIG. 4 and Table 2.

[0014]

[Table 2]

As is clear from FIG. 4 and Table 2, if the thickness of the aluminum cap is 250 μm, the electron beam cannot pass therethrough and sterilization cannot be performed. On the other hand, it can be seen that sterilization is completed with the aluminum cap having a thickness of 150 μm.

Here, the electron beam sterilization amount required for sterilization will be described. B. pumilus (spo which is an indicator bacterium of radiation sterilization
The D value of (res) is 1.7 kGy. Sterilization means reducing the number of viable bacteria per product to ^10-6 .
The required electron dose is 1.7 × 6 = about 10 kGy. The surface of the aluminum cap is irradiated with a dose of 10 kGy or more, but the dose that reaches the rubber plug through aluminum is 1
It is also suggested from the sterilization rate that it is 0 kGy or less. Therefore, since only a small dose has reached the rubber stopper, there is no need to worry about deterioration of butyl rubber.

The thickness of the metal cap is 150 in terms of areal density.
˜600 g / m ² is desirable in FIG.
As is clear from the electron beam dose-penetration depth characteristic graph shown in Fig. 6, when the surface density is 150 g / m ² or less, the mechanical strength cannot be maintained, and when it is 600 g / m ² or more, low energy electrons of 300 kV are generated. This is because the line does not have sufficient penetrating power.
Further, considering the mechanical strength of the cap, it is advantageous that a large wall thickness can be secured, so a metal having a specific gravity as small as possible is desirable. For example, aluminum, titanium and their alloys. Further, the acceleration voltage of a low energy electron beam is preferably 300 kV or less, and if it exceeds this, it becomes difficult to form a self-shielding structure.

[0018]

As is clear from the above description, in the sterilization method according to the present invention, the vial is selected by selecting the thickness of the cap so that the low-energy electron beam can pass through the cap and not through the rubber stopper. It is possible to completely sterilize the surface of the vial and the gap between the upper surface of the rubber stopper and the cap without affecting the medicine sealed inside the bottle. Further, since the electron beam irradiation device used for the sterilization treatment is a compact low energy type device adopting a self-shielding structure, there is an advantage that the in-line production process can be easily performed.

[Brief description of drawings]

FIG. 1 is a schematic view of an electron beam irradiation apparatus used in a sterilization method according to the present invention.

FIG. 2 is a schematic view of the same vial.

FIG. 3 is a characteristic diagram of electron beam dose-penetration depth.

FIG. 4 is a characteristic diagram showing a relationship between irradiation dose and viable cell count.

[Explanation of symbols]

 1 vial bottle 2 metal cap 3 rubber stopper 10 electron beam generator 20 irradiation chamber 30 irradiation window

Claims (3)

[Claims] 1. A method for sterilizing a vial in which the opening of a vial containing a drug is sealed via a rubber stopper and a metal cap covering the upper surface of the vial, and a low-energy electron beam is irradiated from the outer surface of the cap. A method of sterilizing a vial, characterized in that the thickness of the cap of the vial is selected so that the electron beam penetrates and does not pass through a rubber stopper. 2. The wall thickness of the metal cap is 15 in terms of areal density.
The method for sterilizing a vial according to claim 1, wherein the method is specified to 0 to 600 g / m ² . 3. The acceleration voltage of the low energy electron beam is 3
The method for sterilizing a vial according to claim 1 or 2, which has a voltage of 00 kV or less.