JP4575003B2 - Method and apparatus for filling contents into glass container - Google Patents

Description

  The present invention relates to a filling method and a filling device for filling a glass container with contents such as a liquid and sealing it, and more particularly to a filling method and a filling device for filling a chemical solution in a glass ampoule and sealing it.

The active ingredient in the chemical solution is oxidized by oxygen, and the titer often changes over time. For example, stannous chloride, which is a reducing agent, is usually present as Sn ^{2+ in a} chemical solution as an active ingredient, but is oxidized and present as Sn ⁴⁺ in the presence of oxygen, thereby reducing ability (potency) as a reducing agent. ) Decreases. When a drug is prepared using a drug solution having a reduced titer in this way, a drug having a target efficacy cannot be obtained, resulting in a drug having a low chemical purity. There is a need to provide a solution that does not change.

  Conventionally, as a filling container for a chemical solution that does not like oxidation with oxygen as described above, a filling container using a gas (oxygen) permeable material (such as a rubber stopper) is not used, and the material does not have gas permeability. For example, glass ampules or the like are used. However, there is a problem that the chemical solution filled in such a glass ampule is oxidized by oxygen existing in a space layer other than the chemical solution layer in the ampule, so that the amount of oxygen existing in the space layer can be increased. It is necessary to reduce as much as possible.

  Until now, in order to eliminate the harmful effects of oxygen present in the headspace in containers filled with contents that are easily affected by oxygen, an inert gas such as nitrogen is sealed in the container before sealing the container. To replace the gas in the head space with an inert gas, for example, a technique of filling a liquid in an easily deformable container such as an infusion bag or a plastic bottle (Patent Document 1: Japanese Patent Laid-Open No. Hei 5). -170228, etc.), technology for filling a non-pressure-resistant container such as a paper pack (Patent Document 2: JP-A-10-218288, Patent Document 3: JP-A-10-218289, etc.), bottles, etc. In which a container such as fruit juice or carbonated beverage is filled and sealed with a cap (Patent Document 4: Japanese Patent Laid-Open No. 64-9196, Patent Document 5: Japanese Patent Laid-Open No. 1-279018) Patent Document 6: JP-A-6-345192 Publication), and the like are known.

  However, when filling a glass container such as a glass ampoule with liquid or the like, that is, when sealing the glass container itself without using a cap, the amount of oxygen present in the space layer should be reduced. So far, no satisfactory technology has been proposed. When filling a glass container such as a glass ampoule with a liquid or the like and sealing it, the opening of the glass container is heated to a high temperature, unlike the case of a bottle sealed with a plastic bottle, paper pack, or cap. Therefore, when the inert gas for replacing the air in the container is supplied, the opening of the heated glass container is cooled by the inert gas. There was a problem that heating was hindered.

JP-A-5-170228 Japanese Patent Laid-Open No. 10-218288 Japanese Patent Laid-Open No. 10-218289 JP-A 64-9196 Japanese Patent Laid-Open No. 1-279018 JP-A-6-345192

  The present invention has been made in view of the above-described circumstances, and after filling a glass container such as a glass ampoule with contents such as a liquid, the opening is heated and melted to be fused. An object of the present invention is to provide a filling method and a filling device that can reduce the amount of oxygen present in a space layer other than a liquid layer in a glass container as much as possible when the container is sealed.

  As a result of intensive studies to solve the above-mentioned problems, the inventors have filled the glass container with contents such as a liquid, and then heated and melted and fused the opening of the glass container. Inserting a gas nozzle for discharging an inert gas into the glass container and sealing the opening of the glass container while replacing the air in the glass container with an inert gas, When the inert gas is continuously discharged from the gas nozzle into the glass container until the opening is closed, the heated glass container is not cooled by the inert gas and the heating is not hindered. Furthermore, the present inventors have found that the amount of oxygen present in the space layer other than the liquid layer in the sealed glass container can be reduced as much as possible, and have completed the present invention.

The present invention has been made on the basis of the above knowledge, and the contents are filled into the glass container including a sealing step of sealing by heating, melting and welding the opening of the glass container filled with the contents. In the sealing step, a gas discharge port of a gas nozzle that discharges an inert gas is inserted into a glass container, and the inert gas is discharged from the gas discharge port into the glass container. Is started to seal the opening of the glass container while replacing the inert gas , and the inert gas is discharged into the glass container from the gas outlet until the sealing of the opening of the glass container is completed , and The gas discharge port of the gas nozzle is inserted below the sealing position of the opening of the glass container and then rises while discharging the inert gas. When the sealing of the opening of the glass container is finished, the glass container Provides a method of filling contents into the glass container, characterized in that disposed above the blocked position of the opening of the.

The present invention also relates to a filling device that seals by heating, melting and welding the opening of a glass container filled with the contents, and is a gas nozzle capable of discharging an inert gas and inserting it into the glass container A sealing step having a heating means for heating the opening of the glass container and a holding means for supporting the opening of the glass container, and the gas discharge port of the gas nozzle is inserted into the glass container in the sealing step And starting the sealing of the opening of the glass container while discharging the inert gas from the gas outlet into the glass container and replacing the air in the glass container with the inert gas, and sealing the opening of the glass container There discharging the inert gas into the glass container from the gas outlet to the end, and the gas outlet of the gas nozzle was inserted below the sealed position of the opening of the glass container , It increased while discharging the inert gas, when the blockage of the opening of the glass container is completed the contents into a glass container, characterized in that disposed above the blocked position of the opening of the glass container A filling device is provided.

  According to the filling method and the filling apparatus of the present invention, after filling the glass container with contents such as liquid, when sealing the glass container by heating and melting and welding the opening of the glass container, The amount of oxygen present in the space layer other than the liquid layer in the glass container can be reduced as much as possible.

  The present invention will be described in detail below. In the filling method of the present invention, the opening of a glass container such as a glass ampoule filled with a certain amount of contents such as a chemical solution is heated and melted by a flame of a gas burner and then sealed. A sealing step (hereinafter also referred to as fusing) is included. Further, the filling device of the present invention includes a gas nozzle capable of discharging an inert gas and inserting it into the glass container, a heating means for heating the opening of the glass container, and a clamping means for supporting the glass container with the opening. The sealing step can be carried out in the blocking step.

  In the sealing step, a gas nozzle that discharges an inert gas such as argon, nitrogen, or helium is inserted into the glass container filled with contents such as a chemical solution in the previous step. Then, by discharging the inert gas from the gas nozzle into the glass container, while replacing the air in the glass container with the inert gas, the opening of the glass container is sealed, that is, the molten glass container is melted. Start wearing. In this case, the inert gas is constantly discharged from the gas nozzle into the glass container after the inert gas starts to be discharged into the glass container until the opening of the glass container is closed.

  As described above, when the gas nozzle for discharging the inert gas is inserted into the glass container, the inert gas does not directly contact the opening of the glass container, so that the opening of the glass container is not cooled by the inert gas. It is melted and heated to a sufficient temperature.

  Further, by inserting a gas nozzle for discharging the inert gas into the glass container, it is possible to reliably discharge the inert gas into the glass container and replace the air in the glass container with the inert gas at a high rate. . Furthermore, by always discharging the inert gas until the opening of the glass container is closed, the air in the glass container can be replaced with the inert gas until the opening of the glass container is closed. Therefore, according to the present invention, the amount of oxygen existing in the space layer other than the liquid layer in the glass container can be reduced as much as possible.

  In the present invention, the gas discharge port at the tip of the gas nozzle inserted into the glass container is not in contact with the liquid surface of the chemical liquid or the like filled in the glass container, and is sealed at the opening of the glass container, that is, heated. It is preferable to be inserted below the position where the liquid is positioned, and it is more preferable that the liquid level be as close as possible. In this way, the closer the gas discharge port at the tip of the gas nozzle is below the sealing position of the opening of the glass container and the closer to the liquid level of the chemical solution, the more completely the air in the glass container is replaced with an inert gas. This can further reduce the residual oxygen ratio of the space layer in the glass container.

  Also, if the gas discharge port of the gas nozzle is inserted as close to the liquid surface as possible, the sealing position of the opening of the glass container and the discharge port of the inert gas are further away, so that the opening of the glass container is not suitable. It is possible to reduce the influence of the active gas, that is, the phenomenon of being cooled by the inert gas until the glass container opening is heated to a temperature sufficient for melting. Thus, if the opening of the glass container is not cooled and heating is not hindered, the sealing time of the opening will not be longer than necessary, and the filling speed of the filling device will not be reduced. Therefore, the production capacity of the filled container can be maintained high.

  As described above, when the gas discharge port of the gas nozzle is inserted below the sealing position of the opening of the glass container, the gas discharge port of the gas nozzle rises while discharging the inert gas, and seals the opening of the glass container. When is finished, it is preferably arranged above the blocking position of the opening of the glass container. In this case, since the gas discharge port of the gas nozzle passes close to the sealing position of the opening immediately before the sealing of the opening of the glass container is completed, the inert gas temporarily contacts the sealing position. Since the part has already been heated sufficiently for melting, it can be welded with almost no influence of cooling by the inert gas.

  Further, in the sealing step, the inert gas is preferably discharged from the gas nozzle before the gas nozzle is inserted into the glass container, thereby further reducing the residual oxygen ratio of the space layer in the glass container. Can do.

  Furthermore, in the sealing step, it is preferable that the timing of stopping the discharge of the inert gas from the gas nozzle is stopped immediately after the sealing of the opening of the glass container is completed. Thereby, it can prevent that an inert gas contacts the sealing part of the glass container which has not cooled completely by heating, and the shape of a sealing part deform | transforms.

  The flow rate of the inert gas discharged from the gas nozzle in the sealing step is appropriately set according to the capacity of the glass container, the amount of filling liquid, and the volume of the space layer other than the liquid layer in the glass container. In the case of a glass container with a maximum capacity of 70 mL, the filling liquid amount is 40 to 50 mL, and the space layer volume is 20 to 30 mL, it is preferably discharged in the range of 1 to 3 L / min, more preferably 2.0 to 2.5 L / min. If the flow rate of the inert gas is less than 1 L / min, the residual oxygen rate in the space layer in the glass container is increased, which is not preferable. If it exceeds 3 L / min, the thickness of the sealed portion after the end of the opening of the glass container is closed. Since the glass container becomes thin, the glass container may be easily broken, and the shape of the glass container may not be good.

The filling method of the present invention can include, for example, the following steps as a pre-step of the blocking step.
(1) Replacement step before filling: A step in which the inside of the glass container is brought into a negative pressure state before the contents are filled in the glass container, and then the inert gas is discharged into the glass container.
(2) Filling step: A step of filling the contents in the glass container and simultaneously discharging the inert gas to replace the air in the glass container with the inert gas.
(3) Post-filling replacement step: a step of discharging the inert gas into the glass container filled with the contents and replacing the air in the glass container with the inert gas.

Moreover, the filling apparatus of this invention can be equipped with the following process parts, for example corresponding to the pre-process of the said blockade process.
(1) Pre-filling replacement process part: a process part in which the inside of the glass container is brought into a negative pressure state before the contents are filled into the glass container, and then the inert gas is discharged into the glass container.
(2) Filling process part: The process part which discharges an inert gas at the same time as filling the contents in a glass container, and replaces the air in a glass container with an inert gas.
(3) Post-fill replacement step: A step for discharging the inert gas into the glass container filled with the contents and replacing the air in the glass container with the inert gas.

  Hereinafter, although an embodiment of the present invention is described in more detail based on a drawing, the present invention is not limited to the following example. 1 to 5 show an example of a filling device according to the present invention, and show a filling device that seals an opening of a 50 mL ampoule (maximum capacity: 70 mL) filled with a chemical solution by fusing.

  FIG. 1 is a schematic plan view showing the configuration of an example of a filling apparatus according to the present invention. The outline of the filling apparatus 1 of this example will be described. The pre-filling replacement process unit 10, the filling process unit 20, and the post-filling replacement There are a plurality of ampule placement portions 4 that are provided with a process portion 30 and a blockade step portion 40, and the ampules are placed on the periphery of the rotary disc base 2, and each step of the ampule is performed by rotating the disc base 2. The units are configured to move sequentially. The ampoule supply unit 60 for supplying the ampoule to the ampoule arrangement unit 4 and the ampoule discharge unit 70 for discharging the ampoule from the ampoule arrangement unit 4 are provided. The ampoule arrangement unit and the ampoule discharge unit are a rotary disk. It is comprised from the stand 6 and 8. Hereinafter, each process part will be described.

(Replacement process part before filling)
FIG. 2 is a longitudinal sectional view on the center line of the ampoule 11 when the ampoule 11 is arranged in the pre-filling replacement process unit 10. In FIG. 2, a cylindrical pad 13 connected to a vacuum pump (not shown) at the vacuum pump connection portion 12 to suck air in the ampoule 11 and the pad 13 is inserted into the pad 13 from above. A gas nozzle 14 for discharging argon gas is provided in the pad 13. The pad 13 has a structure that can move up and down. The pad 13 is lowered from above the ampoule 11 arranged in the ampoule arrangement part 4 on the disk base 2 and covers this part so as to be in close contact with the shoulder part of the ampoule 11. 11 is arranged to seal. The pad 13 is provided with a silicone packing 15 at a portion that is in close contact with the ampoule 11 so that the ampoule 11 can be securely sealed. After sealing, the air inside the ampoule 11 is sucked by a vacuum pump and the inside of the ampoule 11 is hidden. Pressure state.

  The gas nozzle 14 has a structure that can move up and down. The gas nozzle 14 descends from above the ampoule 11 that has been in a negative pressure state by a vacuum pump, is inserted into the ampoule 11, and rises while discharging argon gas from the gas outlet 16 at the tip. To do. Further, after the argon gas is discharged from the gas nozzle 14 and the inside of the pad 13 becomes slightly positive pressure, the pad 13 rises following the gas nozzle 14. After the argon gas is discharged from the gas nozzle 14, both the gas nozzle 14 and the pad 13 are raised. The ampule 11 is arranged above the ampule 11.

  2A is a view showing a state in which the air inside the ampoule 11 is sucked by the vacuum pump so that the inside of the ampoule 11 is in a negative pressure state. At this time, the gas nozzle 14 is disposed above the ampoule 11. ing. FIG. 4B is a diagram showing a state where the gas nozzle 14 is lowered from above the ampoule 11 in a negative pressure state and inserted into the ampoule 11.

(Filling process part)
3 is an overall longitudinal sectional view of the nozzle 21 provided in the filling process section 20, FIG. 4 is an enlarged longitudinal sectional view of the discharge port at the tip of the nozzle 21, and FIG. 5 is a sectional view taken along line AA in FIG. . The nozzle 21 in the filling process unit 20 includes a chemical solution supply unit 22 to which a chemical solution is supplied and a gas supply unit 23 to which an argon gas is supplied, and discharges the chemical solution filling nozzle 24 for filling the chemical solution and the argon gas. The gas nozzle 25 is provided with a double nozzle discharge port 26 in which the discharge port of the chemical solution filling nozzle 24 and the discharge port of the gas nozzle 25 are integrated. The double nozzle discharge port 26 is provided with a discharge port of the gas nozzle 25 around the discharge port of the chemical solution filling nozzle 24 so that the chemical solution and the argon gas can be discharged simultaneously. The nozzle 21 having the double nozzle discharge port 26 is movable up and down, and the double nozzle discharge port 26 is inserted into the ampoule 11 moved from the pre-filling replacement process unit 10, and the chemical solution is discharged from the double nozzle discharge port 26. And the argon gas are discharged simultaneously, the nozzle 21 rises, and the nozzle 21 is arranged above the ampoule 11 after filling with the chemical solution.

(Post-fill replacement process part)
FIG. 6 is a longitudinal sectional view on the center line of the ampoule 11 when the ampoule 11 is arranged in the post-filling replacement process unit 30. The post-filling replacement process unit 30 includes a gas nozzle 31 through which argon gas is discharged. The gas nozzle 31 has a structure that can move up and down, is inserted into the ampoule 11 filled with the chemical solution 32 that has moved from the filling process unit 20, and rises while discharging argon gas from the gas discharge port 33 at the tip. The ampule 11 is arranged above the ampule 11.

(Blockade Process Department)
FIG. 7 is a longitudinal sectional view and a plan view on the center line of the ampoule 11 when the ampoule 11 is disposed in the sealing step section 40. The sealing process unit 40 includes a gas nozzle 41 for discharging argon gas, a burner 42 that is a heating unit that heats the opening of the ampoule 11, and a pincher 43 that is a clamping unit that supports the opening of the ampoule 11 from both sides. I have. Further, the ampoule placement part 4 where the ampoule 11 is placed has a rotating structure, and the ampoule 11 is always rotating in the sealing process part 40.

  The gas nozzle 41 has a structure that can move up and down, is inserted into the ampoule 11 filled with the chemical liquid 45 that has moved from the post-filling replacement process unit 30, and rises while discharging argon gas from the gas discharge port 46 at the tip. It has a configuration. Further, the gas nozzle 41 starts discharging the argon gas before being inserted into the ampoule 11.

  The burner 42 serving as a heating means heats and melts a fixed position (heating unit 44) of the opening of the rotating ampoule 11. Further, the pincher 43 serving as the clamping means has a structure that can support the opening of the ampoule 11 from both sides, and ascends from the both sides of the upper part of the heating part 44 of the ampoule 11.

  Further, in the sealing step section 40, the argon gas is constantly discharged from the gas nozzle 41 into the ampoule 11 after the argon gas starts to be discharged from the gas nozzle 41 until the opening of the ampoule 11 is closed. Yes.

  7A is a longitudinal sectional view and a plan view showing a state where a certain position of the opening of the rotating ampule 11 is heated by the burner 42. FIG. (B) is a longitudinal sectional view and a plan view showing a state where the gas nozzle 41 is inserted into the ampoule 11 and the pincher 43 sandwiches the upper part from the heating part 44 of the ampoule 11 from both sides. (C) is a longitudinal sectional view and a plan view showing a state in which the gas nozzle 41 is disposed above the ampoule 11 and the pincher 43 is lifted from both sides above the heating part 44 of the ampoule 11.

  Next, an example of a filling method for filling an ampoule with a chemical solution using the filling device of this example configured as described above will be described.

(1) Pre-fill replacement step The pre-fill replacement step is performed in the pre-fill replacement step unit 10 shown in FIGS. An empty 50 mL ampoule 11 (filling portion bottom surface inner diameter φ34.2 mm, filling portion height 135.0 mm, opening diameter φ10.0 mm) is supplied from the ampoule supply unit 60 and arranged in the ampoule arrangement unit 4, and the vacuum pump connection unit 12 is moved below the cylindrical pad 13 connected to the vacuum pump. The pad 13 is arranged so as to descend from above the ampoule and adhere to the shoulder portion of the ampoule 11 so as to cover and seal the ampoule 11. Then, the air inside the ampoule 11 is sucked at 450 mmHg by a vacuum pump, and the inside of the ampoule 11 is brought into a negative pressure state.

  Next, the gas nozzle 14 inserted into the pad 13 is inserted into the ampoule 11, and the gas discharge port 16 of the gas nozzle 14 is disposed at a position 30 mm above the bottom surface of the ampoule 11. Suction by the vacuum pump is stopped, and then argon gas is discharged from the gas nozzle 14 at a flow rate of 5 L / min. At the same time as the argon gas is discharged, the gas nozzle 14 starts to rise, and when the gas discharge port 16 of the gas nozzle 14 reaches a position 65 mm above the bottom surface of the ampoule 11, the discharge of the argon gas is stopped. Further, after the argon gas is discharged and the inside of the pad 13 is set to a slight positive pressure, the pad 13 rises while following the gas nozzle 14. After the gas nozzle 14 and the pad 13 move above the ampoule 11, the disk base 2 rotates and the ampoule 11 placed in the ampoule placement part 4 is sent to the next step.

(2) Filling Step The filling step is performed in the filling step section 20 shown in FIGS. 1 and 3 to 5. The ampoule 11 sent from the pre-filling replacement process unit 10 in the above (1) includes a chemical solution supply unit 22 to which a chemical solution is supplied and a gas supply unit 23 to which an argon gas is supplied, and is filled with a chemical solution. The discharge port of the nozzle 24 and the discharge port of the gas nozzle 25 that discharges argon gas are disposed below the double nozzle discharge port 26. The double nozzle outlet 26 descends from above the ampoule 11 and is inserted into the ampoule 11, and the tip of the double nozzle outlet 26 is disposed at a position 30 mm above the bottom of the ampoule 11.

  Thereafter, the chemical solution and the argon gas are simultaneously discharged from the double nozzle discharge port 26, and the nozzle 21 is raised simultaneously with the discharge of the chemical solution and the argon gas. At this time, the argon gas is discharged at a flow rate of 5 L / min. Further, when filling the chemical liquid, the so-called liquid is always filled with the chemical liquid while ascending so as not to come into contact with the liquid level of the chemical liquid filled with the double nozzle discharge port 26. Surface following filling is performed. By performing the liquid surface following filling, foaming of the filling liquid and gas mixing into the filling liquid can be reduced.

  When the tip of the double nozzle discharge port 26 reaches a position 65 mm above the bottom surface of the ampoule 11, the discharge of the chemical solution and the argon gas is stopped, whereby the chemical solution is filled up to a position 50 mm above the bottom surface of the ampoule 11. If argon gas is discharged near the opening in the ampule 11 (the ampule branch), air may be drawn from the outside of the ampule 11, and therefore, the argon gas is discharged at a position below the branch of the ampule 11. It is preferable to stop the discharge. After the double nozzle discharge port 26 moves above the ampoule 11, the disk base 2 rotates and the ampoule 11 arranged in the ampoule arrangement part 4 is sent to the next process.

(3) Post-filling replacement process The post-filling replacement process is performed in the post-filling replacement process unit 30 shown in FIGS. The ampoule 11 sent from the filling process unit 20 in (2) is arranged below the gas nozzle 31 from which argon gas is discharged. The gas nozzle 31 descends from above the ampoule 11 and is inserted into the ampoule 11, and is arranged at a position 10 mm above the liquid level of the chemical solution filled with the gas discharge port 33 at the tip of the gas nozzle 31. Thereafter, argon gas is discharged from the gas nozzle 31 at a flow rate of 5 L / min. At the same time as the argon gas is discharged, the gas nozzle 31 starts to rise, and when the gas discharge port 33 at the tip of the gas nozzle 31 reaches a position 15 mm above the liquid surface of the chemical solution, the discharge of the argon gas is stopped. After the gas nozzle 31 moves above the ampoule 11, the disk base 2 rotates and the ampoule 11 placed in the ampoule placement part 4 is sent to the next step.

(4) Blocking process The blocking process is performed in the blocking process unit 40 shown in FIGS. 1 and 7. The ampule 11 sent from the post-filling replacement process section 30 in (3) above is disposed below the gas nozzle 41 from which argon gas is discharged. The ampoule 11 is always rotated by the rotation of the ampoule arrangement portion 4. The blockade is performed as follows.

(A) Immediately after the ampoule 11 is moved to the blockade process part 40, the fixed position (heating part 44) of the opening part of the ampoule 11 begins to be heated by the burner 42 (FIG. 5a).
(A) The gas nozzle 41 that discharges argon gas is inserted into the ampoule 11 from above the ampoule 11, and the gas discharge port 46 at the tip of the gas nozzle 41 is at a position (liquid level) 18 mm below the heating unit 44 (blocking position). 87.0 mm above). Argon gas is discharged at a flow rate of 2.5 L / min before the gas nozzle 41 is inserted into the ampoule 11.
(C) When the heating part 44 of the ampoule 11 is melted, the upper part of the heating part 44 of the ampoule 11 is sandwiched from both sides by the pincher 43 (FIG. 5b).
(D) After the gas nozzle 41 rises and the gas discharge port 46 is arranged above the heating part 44 of the ampoule 11, the pincher 43 rises while sandwiching the upper part from the heating part 44 of the ampoule 11, and at the same time the gas nozzle 41 also To rise.
(E) When the pincher 43 rises across the upper part of the heating part 44 of the ampoule 11, the heated heating part 44 of the ampoule 11 is pulled upward and extends thinly. A part of the heating part 44 that extends thinly is further cut by being heated by the burner 42, and the opening of the ampoule 11 is blocked (FIG. 5c).
(F) Argon gas is always discharged until the opening of the ampoule 11 is closed, and is stopped immediately after the closing.

  The ampoule 11 whose sealing has been completed and the filling of the chemical solution has been completed as described above is sent to the ampoule discharge unit 70 as the disk base 2 rotates, and is discharged. In this example, two ampoules can be processed simultaneously per process, the blocking process is performed in about 3 seconds, and the process from the start of the pre-filling replacement process to the end of the blocking process is 15.2 seconds. Could be done. The filling amount of the chemical solution in the sealed ampule was 40 mL, and the space layer volume other than the liquid layer was 28 mL.

(Example 1, reference example )
A chemical solution was filled in a 50 mL ampoule by the filling apparatus and the filling method shown in FIGS. 1 to 7, and the amount of oxygen present in the space layer in the ampoule was measured. In the sealing step, the insertion position of the gas discharge port of the gas nozzle into the ampule is the case where the gas discharge port of the gas nozzle is inserted at a position 18 mm below the heating portion (blocking position) in the ampule, as Example 1. The case where it inserted in the position of the heating part of this was made into the reference example . In this case, in the sealing step, the flow rate of the argon gas discharged from the gas nozzle is 2.5 L / min, and the discharge of the argon gas starts before the gas nozzle is inserted into the ampoule, and after the ampoule has been sealed. It was terminated immediately. The amount of oxygen present in the space layer in the ampoule was measured by destroying the ampule in water and collecting only the gas in the space layer, and measuring the amount of oxygen with a calibrated oxygen concentration meter. The amount of oxygen present in the space layer was expressed as the oxygen abundance (%). The results are shown in Table 1.

(Comparative Example 1)
In the sealing step, the ampule was filled with a chemical solution in the same manner as in Example 1 except that argon gas was not discharged from the gas nozzle, and the amount of oxygen present in the space layer in the ampule was measured. The results are shown in Table 1.

(Comparative Example 2)
In the sealing process, the ampoule was filled with a chemical solution in the same manner as in the reference example , except that the discharge of argon gas from the gas nozzle was terminated before the ampoule was sealed, and the amount of oxygen present in the space layer in the ampoule was determined. It was measured. The results are shown in Table 1.

From these results, according to the present invention (Example 1) , when the argon gas was not discharged (Comparative Example 1), and when the discharge of the argon gas was terminated before the ampoule was closed ( Compared to Comparative Example 2), it was confirmed that the oxygen abundance in the space layer in the ampoule was lower.

(Test Example 1)
In the sealing step, the insertion position of the gas discharge port at the tip of the gas nozzle into the ampule is 10 mm above the heating section (blocking position) in the ampule, 7 mm above, 5 mm above, the heating section (0 mm), and the heating section as follows. The ampule was filled with a chemical solution in the same manner as in Example 1, and the amount of oxygen present in the space layer in the ampule was measured. The results are shown in Table 2.

  From the result of Test Example 1, when the gas discharge port of the gas nozzle is inserted 4 mm or more below the position of the heating part in the ampoule, the oxygen abundance in the space layer in the ampoule becomes as low as 0.1% or less. It was confirmed. In addition, when the gas discharge port of the gas nozzle is between a position 2 mm below the position of the heating part in the ampoule and a position 5 mm above the position of the heating part, the oxygen ratio existing in the space layer in the ampoule is 0.1 to 0.1%. It was confirmed to be 0.2%, and it was generally found that the drug solution titer did not change within the storage period of the drug solution.

(Test Example 2)
In the sealing step, the flow rate of argon gas was changed as follows, and the ampule was filled with a chemical solution in the same manner as in Example 1, and the shape of the ampule sealed portion was confirmed. The results are shown in Table 3.

  From the results of Test Example 2, it was found that when the flow rate of the inert gas was less than 3 L / min, the ampule sealed portion became a thick spherical surface and had a good shape that was not easily damaged. On the other hand, when the flow rate of the inert gas exceeds 5 L / min, it was found that the glass at the tip of the ampoule becomes thin and easily breaks because a recess is formed in the melted portion.

It is a typical top view which shows the structure of an example of the filling apparatus which concerns on this invention. It is a longitudinal cross-sectional view on the centerline of the ampule when the ampule is arranged in the pre-filling replacement process section, and (a) shows a state in which the inside of the ampule is sucked by a vacuum pump and the inside of the ampule is in a negative pressure state. FIG. 5B is a diagram showing a state where the gas nozzle is lowered from above the ampoule in a negative pressure state and inserted into the ampoule. It is a whole longitudinal cross-sectional view of the nozzle with which the filling process part was equipped. It is the longitudinal cross-sectional view which expanded the discharge port of the nozzle front-end | tip. It is sectional drawing in the AA of FIG. It is a longitudinal cross-sectional view on the centerline of the ampule when the ampule is arranged in the post-filling replacement process section. It is the longitudinal cross-sectional view and top view on the centerline of an ampule at the time of an ampule being arrange | positioned in a blockade process part, (a) is a figure which shows the state which is heating the fixed position of the opening part of a rotating ampule with a burner (B) is a diagram showing a state in which the gas nozzle is inserted into the ampule and the pincher sandwiches the upper part of the heating portion of the ampule from both sides, and (c) is a diagram in which the gas nozzle is arranged above the ampule and the pincher is It is a figure which shows the state raised across the upper part from the heating part of the ampoule from both sides.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Filling device, 2, 6, 8 ... Disk base, 4 ... Ampoule arrangement | positioning part, 10 ... Pre-filling substitution process part, 11 ... Ampoule, 12 ... Vacuum pump connection part , 13 ... Pad, 14 ... Gas nozzle, 15 ... Silicone packing, 16 ... Gas discharge port, 20 ... Filling process part, 21 ... Nozzle, 22 ... Chemical solution supply part, 23 ... Gas supply unit, 24 ... Chemical solution filling nozzle, 25 ... Gas nozzle, 26 ... Double nozzle outlet, 30 ... Post-filling replacement process unit, 31 ... Gas nozzle, 32 ..Chemical solution 33 ... Gas discharge port 40 ... Sealing process part 41 ... Gas nozzle 42 ... Burner 43 ... Pincher 44 ... Heating part 45 ... Chemical liquid 46 ... Gas discharge port, 60 ... Ampoule supply unit, 70 ... Amp Discharge unit

Claims (11)

A method for filling contents into a glass container including a sealing step of sealing by heating, melting and welding an opening of a glass container filled with the contents, wherein in the sealing step, an inert gas is used. Insert the gas discharge port of the gas nozzle to be discharged into the glass container, discharge the inert gas into the glass container from the gas discharge port, and replace the air in the glass container with the inert gas. Initiating sealing and discharging the inert gas from the gas outlet into the glass container until the sealing of the opening of the glass container is completed , and the gas outlet of the gas nozzle is used to seal the opening of the glass container after being inserted below the position, raised while discharging the inert gas, when the blockage of the opening of the glass container is completed which is arranged above the sealed position of the opening of the glass container Filling method of the contents of the glass container, characterized. 2. The method for filling contents into a glass container according to claim 1 , wherein in the sealing step, the inert gas is discharged from the gas nozzle before the gas nozzle is inserted into the glass container. 3. The filling of the contents into the glass container according to claim 1, wherein in the sealing step, the discharge of the inert gas from the gas nozzle is stopped immediately after the opening of the glass container is closed. Method. As a pre-process of the sealing process, before filling the contents in the glass container, the glass container is placed in a negative pressure state, and then the inert gas is discharged into the glass container. At the same time as filling the material, the inert gas is discharged to replace the air in the glass container with the inert gas, and the inert gas is discharged into the glass container filled with the contents, The method for filling contents into a glass container according to any one of claims 1 to 3 , wherein a post-filling replacement step of replacing the air with an inert gas is sequentially performed. The filling step has a filling nozzle for filling the contents and a gas nozzle for discharging the inert gas, and the discharge port of the filling nozzle and the discharge port of the gas nozzle are the contents and the inert gas. The contents are filled while rising so as to be positioned above the liquid level of the contents so as not to come into contact with the liquid level of the filled contents. To fill the glass container with the contents. The filling step has a filling nozzle for filling the contents and a gas nozzle for discharging an inert gas, and the discharge port of the filling nozzle and the discharge port of the gas nozzle are integrated. The method for filling contents into a glass container according to claim 4 or 5, comprising a nozzle outlet. A filling device that seals a glass container filled with contents by heating, melting, and fusing it, a gas nozzle that discharges an inert gas and can be inserted into the glass container, and an opening of the glass container A sealing process unit having a heating unit for heating the glass container and a sandwiching unit for supporting the glass container with the opening of the glass container interposed therein, and the gas discharge port of the gas nozzle is inserted into the glass container in the sealing process unit, The gas is discharged into the glass container to start sealing the opening of the glass container while replacing the air in the glass container with the inert gas, and the gas is sealed until the opening of the glass container is closed. the inert gas in the glass vessel was discharged from the discharge port, and the gas outlet of the gas nozzle, after being inserted below the sealed position of the opening of the glass container, the inert gas Out while rising, filling device contents into a glass container when the blockage of the opening of the glass container is finished, characterized in that disposed above the blocked position of the opening of the glass container. As a pre-process part of the sealing process part, before filling the contents in the glass container, the inside of the glass container is brought into a negative pressure state, and then the pre-fill replacement process part for discharging the inert gas into the glass container, the glass container At the same time as the contents are filled, the inert gas is discharged and the air in the glass container is replaced with the inert gas, and the inert gas is discharged into the glass container filled with the contents. The apparatus for filling contents into a glass container according to claim 7 , further comprising a post-filling replacement process section for replacing air in the glass container with an inert gas in this order. The filling process unit includes a filling nozzle for filling the contents and a gas nozzle for discharging an inert gas, and the discharge port of the filling nozzle and the discharge port of the gas nozzle are inert to the contents. 9. The contents are filled while being raised so as to be positioned above the liquid level of the contents so that the gas rises while discharging the gas at the same time and does not contact the liquid level of the filled contents. The filling device of the contents to the glass container of description. The filling process unit includes a filling nozzle for filling the contents and a gas nozzle for discharging an inert gas, and the discharge port of the filling nozzle and the discharge port of the gas nozzle are integrated. The apparatus for filling contents into a glass container according to claim 8 or 9, comprising a heavy nozzle outlet. A disk base having an ampoule arrangement part at a peripheral part is provided, and the ampoule arranged in the ampoule arrangement part is replaced with the pre-filling replacement process part, the filling process part, the post-filling replacement process part, and the blockage by rotating the disk base. The apparatus for filling contents into a glass container according to any one of claims 8 to 10, wherein the process section is sequentially moved.