A kind of encapsulation needle structure and residual oxygen control method in liquid medicine filling process

Abstract

The application discloses a kind of filling needle structure and residual oxygen control method in liquid medicine filling process, belong to the technical field of medicine filling machinery, including the double-layer spiral flow guide needle for conveying protective gas and liquid medicine, the partial pressure type gas outlet needle for rear protective gas, the protective gas into double-layer spiral flow guide needle is sent out spirally, and the protective gas into partial pressure type gas outlet needle is sent out from its side, bottom surface.The application can effectively overcome the defects of low oxygen removal efficiency of nitrogen filling needle, easy to cause liquid medicine splashing and existence of airflow dead zone in bottle neck area in the existing ampoule filling process.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical filling machinery technology, specifically, it relates to a filling needle structure and a method for controlling residual oxygen during the pharmaceutical filling process. Background Technology

[0002] Ampoules are commonly used packaging containers for liquid medications such as injections, and the control of residual oxygen during the filling and sealing process directly affects the long-term storage stability of these drugs. For oxygen-sensitive drugs like ranitidine hydrochloride injection, the residual oxygen control level under current technology is typically only around 2%. When the drug solution comes into contact with residual oxygen in the bottle, it is prone to oxidative deterioration, which not only leads to reduced efficacy but may also further react to generate harmful substances during the drug's stability study period.

[0003] Current ampoule filling and sealing processes typically employ a "pre-nitrogen filling-post-nitrogen filling" process to control headspace residual oxygen levels. However, in practical applications, conventional nitrogen-filling needles have the following technical shortcomings:

[0004] First, the airflow organization is unreasonable: when using a conventional beveled needle for nitrogen filling, the nitrogen flow field is concentrated in the direction of the needle axis, which easily forms a vortex zone inside the ampoule, causing the air near the bottle opening to mix with the nitrogen, ultimately resulting in low oxygen removal efficiency.

[0005] Secondly, it can easily cause liquid surface disturbance: during the post-nitrogen filling process, the high-speed nitrogen gas directly blowing on the surface of the liquid can easily cause the liquid to splash, resulting in the liquid adhering to the inner wall of the ampoule neck; in the subsequent sealing process, the residual liquid will carbonize at high temperature, producing visible foreign matter or black spots, which directly affects the quality of the medicine.

[0006] Third, there is an airflow dead zone: the neck of the ampoule itself is a long and thin structure, and conventional needles cannot effectively replace the residual air in the neck area. When sealing, this part of the air will mix into the headspace, which will eventually lead to a high residual oxygen content in the headspace, which usually only reaches about 2%.

[0007] Therefore, there is an urgent need for a filling needle structure that can ensure that the residual oxygen inside the ampoule is less than 2% after the filling process is completed, as well as a method for controlling residual oxygen during the drug filling process. Summary of the Invention

[0008] The purpose of this invention is to provide a filling needle structure and a method for controlling residual oxygen during the filling process of medicine, which can effectively overcome the defects of existing ampoule filling processes, such as low oxygen removal efficiency of nitrogen-filled needles, easy splashing of medicine, and airflow dead zone in the bottleneck area.

[0009] To achieve the objective of this invention, the technical solution adopted is as follows: a filling needle structure, comprising a double-layer spiral guide needle for conveying protective gas and liquid medicine, and a pressure-dividing outlet needle for conveying protective gas. The protective gas can be nitrogen or other rare gases. The double-layer spiral guide needle and the pressure-dividing outlet needle can be independently installed on the needle holder of the filling system. The protective gas inlet on the double-layer spiral guide needle and the protective gas inlet on the pressure-dividing outlet needle can be connected in parallel to the same gas supply system. Alternatively, the protective gas inlet on the double-layer spiral guide needle and the protective gas inlet on the pressure-dividing outlet needle can be connected to two separate sets of... The gas supply system features a spiral flow pattern. The protective gas entering the double-layered spiral guide needle is spirally discharged as it passes through the needle, creating an orderly laminar flow field within the ampoule. The protective gas entering the pressure-distributing gas outlet needle can be simultaneously discharged from both the side and bottom surfaces, dispersing the gas pressure and preventing concentrated application of the protective gas to the medication, thus effectively preventing splashing of the medication within the ampoule.

[0010] Preferably, the protective gas delivered by the double-layer spiral guide needle and the protective gas delivered by the pressure-dividing outlet needle can be the same type of gas. In this case, the protective gas inlet of the double-layer spiral guide needle and the protective gas inlet of the pressure-dividing outlet needle can be connected in parallel to the same gas supply system, or the protective gas inlet of the double-layer spiral guide needle and the protective gas inlet of the pressure-dividing outlet needle can be connected to two separate gas supply systems. Of course, while meeting the requirements for filling the medicine, the type of protective gas delivered by the double-layer spiral guide needle and the protective gas inlet of the pressure-dividing outlet needle can be adjusted according to the actual situation. When the types of protective gas delivered by the double-layer spiral guide needle and the protective gas inlet of the pressure-dividing outlet needle are different, the protective gas inlet of the double-layer spiral guide needle and the protective gas inlet of the pressure-dividing outlet needle need to be connected to two separate gas supply systems.

[0011] Furthermore, the protective gas delivered by the double-layer spiral guide needle is used for gas replacement before drug filling: that is, the protective gas output by the double-layer spiral guide needle is used to purge the inside of the ampoule before drug filling, blowing out the oxygen remaining in the ampoule before filling; the protective gas delivered by the pressure-splitting gas outlet needle is used for gas replacement after drug filling, that is, the pressure-splitting gas outlet needle is used to purge the inside of the ampoule after drug filling, blowing out the oxygen remaining in the ampoule and the space above the drug.

[0012] Furthermore, the double-layer spiral guide needle includes an inner tube and an outer tube. The central axis of the inner tube and the central axis of the outer tube are on the same straight line, and the inner diameter of the outer tube is larger than the outer diameter of the inner tube, so that an annular airflow channel is formed between the outer wall of the inner tube and the inner wall of the outer tube. This annular airflow channel is used for the delivery of protective gas, while the inner tube is used for the delivery of liquid medicine.

[0013] Furthermore, the outlet end of the annular airflow channel is also equipped with a spiral flow guiding structure for guiding the protective gas. This allows the protective gas to flow along the axial direction of the outer tube after entering the annular airflow channel. When the protective gas enters the middle section or the outlet section of the annular airflow channel, it flows in a spiral direction. Finally, the protective gas flows in a spiral direction when it is sent out through the annular airflow channel.

[0014] Preferably, while ensuring that the protective gas delivered through the annular airflow channel flows in a spiral direction, the spiral guide structure in this invention may not extend from the inlet end of the outer tube to the outlet end of the annular airflow channel, so that the protective gas can flow in a spiral direction as soon as it enters the annular airflow channel.

[0015] Furthermore, the spiral flow guiding structure includes a spiral partition plate disposed between the outer wall of the inner tube and the inner wall of the outer tube. The inner edge of the spiral partition plate is welded and fixed to the outer wall of the inner tube, and the outer edge of the spiral partition plate is welded and fixed to the inner wall of the outer tube. The spiral partition plate divides the outlet end of the annular airflow channel into multiple spiral guide grooves. The inlet ends of the multiple spiral guide grooves are all connected to the annular airflow channel, so that when the protective gas entering the annular airflow channel passes through the spiral flow guiding structure, the protective gas flows along the spiral guide grooves, thereby causing the protective gas to flow in the spiral direction, and finally causing the protective gas discharged from the annular airflow channel to flow in the spiral direction.

[0016] Furthermore, there are multiple spiral partition plates, which are evenly spaced along the circumference of the annular airflow channel, so that the spiral guide structure divides the outlet end of the annular airflow channel into multiple spiral guide grooves, and the multiple spiral guide grooves are evenly spaced along the circumference of the annular airflow channel.

[0017] Preferably, the number of spiral partition plates is set to 2 to 5, which corresponds to 3 to 6 spiral guide grooves being formed at the outlet end of the annular airflow channel; of course, as long as the usage requirements are met, the number of spiral partition plates can also be set to 1 or more, and the specific number can be adjusted according to the actual usage requirements.

[0018] Furthermore, the helix angle of the spiral guide groove is 30° to 60°, and the specific helix angle of the spiral guide groove can be adjusted according to actual needs.

[0019] Furthermore, the outlet end of the inner tube extends beyond the outlet end of the outer tube, and the outlet end of the inner tube forms the central liquid outlet of the double-layer spiral guide needle.

[0020] Furthermore, the length by which the outlet end of the inner tube extends beyond the outlet end of the outer tube is 2 to 5 mm, and the specific length by which the outlet end of the inner tube extends beyond the outlet end of the outer tube can be adjusted according to the actual situation.

[0021] Furthermore, the outlet end of the inner tube is beveled, with an inclination angle of 15° to 45°. When the double-layer spiral guide needle is inserted into the ampoule, the bevel of the outlet end of the inner tube faces the ampoule wall, allowing the liquid to flow downwards along the ampoule wall as it exits through the inner tube, thereby reducing impact and air bubble generation. In addition, the inclination angle of the bevel can be adjusted according to the actual filling situation of the liquid.

[0022] Furthermore, the pressure-distributing gas outlet needle includes a needle tube, and multiple vent holes are spaced apart along the circumference on the side wall of the needle tube outlet end. All vent holes communicate with the internal channel of the needle tube. By opening vent holes on the side of the needle tube outlet end, the protective gas entering the needle tube can be discharged radially through the multiple vent holes, thereby reducing the airflow of protective gas perpendicular to the liquid medicine. This prevents the protective gas discharged from the pressure-distributing gas outlet needle from causing liquid medicine splashing when replacing oxygen in the space above the liquid medicine inside the ampoule.

[0023] Furthermore, the number of air outlets is 4 to 8, and the multiple air outlets are evenly spaced along the circumference of the needle tube, while the specific number of air outlets can be adjusted according to the actual situation.

[0024] Furthermore, the vent is an elongated flat vent, with the long side of the vent arranged along the axial direction of the needle tube and the short side of the vent arranged along the circumference of the needle tube.

[0025] Furthermore, the width of the air outlet is 0.2 to 0.5 mm and the length is 1.0 to 2.0 mm, and the specific size of the air outlet can be adjusted according to the actual situation.

[0026] Furthermore, the outlet direction of the air vent is inclined downwards relative to the radial direction of the needle tube, and the inclination angle is 15° to 45°.

[0027] Furthermore, the outlet end of the needle tube is also equipped with a closed conical bottom surface to seal it. The circumference of the closed cone is equal to the inner circumference of the needle tube outlet end, and the bottom edge of the closed conical bottom surface is flush with the end face of the needle tube outlet end. The apex of the closed conical bottom surface is located inside the needle tube and extends towards the needle tube inlet end. A central vent hole is opened in the center of the conical bottom surface, which is used to allow the protective gas entering the needle tube to be discharged downward along the needle tube axis.

[0028] Furthermore, the cone angle of the closed conical bottom surface is 100° to 150°, and the specific cone angle of the closed conical bottom surface can be selected according to the actual situation.

[0029] Furthermore, both the double-layer spiral guide needle and the pressure-splitting gas outlet needle also include a needle seat, and the inlet end of the inner tube and the inlet end of the outer tube are fixedly installed on one of the needle seats. The needle seat has a liquid channel communicating with the inner tube, and the needle seat also has a protective gas flow channel communicating with the annular airflow channel. The inlet end of the pressure-splitting gas outlet needle tube is fixedly installed on another needle seat, and the needle seat has a protective gas flow channel communicating with the needle tube.

[0030] Based on the above-described filling needle structure, this invention provides a method for controlling residual oxygen during the drug filling process, comprising the following steps:

[0031] S1. Insert the double-layer spiral guide needle into the ampoule, and position the outlet end of the outer tube of the double-layer spiral guide needle at the junction of the ampoule body and the ampoule neck. The protective gas entering the annular airflow channel is guided by the spiral guide groove to form a spiral airflow, and is ejected from the outlet end of the outer tube in a spiral manner, so that a rotating downward airflow field is formed inside the ampoule, and the air inside the ampoule is discharged from the ampoule mouth to remove oxygen from the empty ampoule.

[0032] S2. The double-layer spiral guide needle stops the delivery of protective gas. The medicine is injected into the ampoule through the inner tube of the double-layer spiral guide needle. The medicine discharged through the inner tube flows down the wall of the ampoule to fill the medicine. The filling speed is 6-12 mL / s.

[0033] S3. The double-layer spiral guide needle stops the delivery of the liquid medicine and is removed. The pressure-splitting gas outlet needle is then inserted into the ampoule, with the outlet end of the pressure-splitting gas outlet needle aligned with the neck of the ampoule. The gas outlet on the needle is positioned 5-10 mm above the liquid medicine surface. The protective gas entering the needle is then ejected through the gas outlet and the central gas outlet. The ejected protective gas forms a covering airflow layer above the liquid medicine surface, performing headspace displacement.

[0034] S4. The pressure-splitting gas outlet needle stops the delivery of protective gas and removes the pressure-splitting gas outlet needle from the ampoule to perform a fusion seal, thus completing the sealing of the ampoule.

[0035] Furthermore, the flow rate of the protective gas through the double-layer spiral guide needle is 5–15 L / min, and the duration is 0.3–0.8 seconds.

[0036] Furthermore, the flow rate of the protective gas through the double-layer spiral guide needle is controlled by a gradient: the flow rate of the protective gas is 8-12 L / min in the initial 0.1 seconds, and then the flow rate of the protective gas is 5-8 L / min, to avoid the air outside the ampoule being drawn into the ampoule due to the excessive airflow velocity of the protective gas at the ampoule mouth.

[0037] Furthermore, the flow rate of the protective gas through the pressure-dividing outlet needle is 3–8 L / min, and the duration is 0.2–0.5 seconds.

[0038] The beneficial effects of this invention are:

[0039] 1. Spiral airflow oxygen removal mechanism: By sending the protective gas into the double-layer spiral guide needle in a spiral shape, the protective gas can move spirally downward along the ampoule wall after entering the ampoule, thereby forming an orderly laminar flow field inside the ampoule, avoiding the turbulent mixing phenomenon caused by conventional direct-blowing nitrogen filling; at the same time, the centrifugal effect of the spiral airflow can push the denser air to the ampoule wall and discharge it upward, while the less dense protective gas is concentrated in the central area, and the oxygen removal efficiency is significantly improved.

[0040] 2. Dispersed gas outlet anti-splash mechanism: The protective gas flowing through the pressure-distributing gas outlet needle can be delivered from the side and bottom of the needle simultaneously, greatly reducing the impact force at a single point; at the same time, the protective gas delivered from the bottom of the needle replenishes the airflow in the central area at a lower flow rate, and the dual effect ensures that there is no splashing on the liquid surface.

[0041] 3. Gradient nitrogen filling strategy: The flow rate of the protective gas through the double-layer spiral guide needle adopts the "high start, low dimension" gradient control. In the initial stage, a high flow rate is used to quickly establish an airflow barrier, and in the subsequent stage, a low flow rate is used to maintain a laminar flow state, which not only ensures oxygen removal efficiency, but also avoids the airflow from entraining external air.

[0042] Compared with the prior art, the present invention has the following beneficial effects:

[0043] 1. Significantly reduces headspace residual oxygen: The spiral airflow output by the double-layer spiral guide needle and the dispersed airflow output by the pressure-distributing outlet needle work together to control the headspace residual oxygen after the ampoule is sealed to 0.5% or less, which is better than the approximately 2% of the traditional process.

[0044] 2. Avoid splashing and contamination of medicine: The double-layer spiral guide needle adopts a double-layer structure, with the airflow channel and the medicine channel separated and not interfering with each other; the pressure-distributing air outlet needle effectively reduces the impact of airflow on the liquid surface through a multi-pore dispersion design, eliminating the problem of medicine splashing and adhering to the inner wall of the bottleneck, and fundamentally solving the quality problem of black spots generated by the fusion seal.

[0045] 3. Reduced nitrogen filling time: After the airflow organization is optimized, the oxygen removal efficiency is improved, and the nitrogen filling time of a single bottle can be reduced by 20% to 30%, which helps to improve the overall filling and sealing production speed.

[0046] 4. Good process adaptability: The needle structure provided by this invention can be adapted to existing ampoule filling machines without major modifications to the main body of the equipment, and has good prospects for industrial application. Attached Figure Description

[0047] The accompanying drawings illustrate exemplary embodiments of the invention and, together with the description thereof, serve to explain the principles of the invention. These drawings are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification.

[0048] Figure 1 This is a schematic diagram of the structure of the double-layer spiral guide needle provided in Embodiment 1 of the present invention;

[0049] Figure 2 This is a schematic diagram of the spiral partition plate.

[0050] Figure 3 This is a schematic diagram of the structure of the pressure-dividing air outlet needle provided in Embodiment 2 of the present invention;

[0051] Figure 4 This is a schematic diagram of a closed conical base.

[0052] The attached diagram shows the markings and corresponding component names:

[0053] 1. Double-layer spiral guide needle; 2. Pressure-dividing air outlet needle;

[0054] 11. Inner tube; 12. Outer tube; 13. Annular airflow channel; 14. Spiral partition plate; 15. Spiral guide groove; 16. Inclined surface;

[0055] 21. Needle tube; 22. Air vent; 23. Closed conical bottom; 24. Central air vent. Detailed Implementation

[0056] The present invention will now be described in further detail with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be noted that, for ease of description, only the parts relevant to the present invention are shown in the accompanying drawings.

[0057] It should be noted that, unless otherwise specified, the embodiments and features described in this invention can be combined with each other. The invention will now be described in detail with reference to the accompanying drawings and embodiments.

[0058] Example 1

[0059] like Figure 1 , Figure 2 As shown, this embodiment provides a double-layer spiral guide needle 1, which is used to transport nitrogen gas and liquid medicine. The nitrogen gas is used for gas replacement before liquid medicine filling. That is, the double-layer spiral guide needle 1 is used for the pre-nitrogen filling and liquid medicine filling process of the ampoule filling machine.

[0060] The double-layer spiral guide needle 1 includes a needle seat, an inner tube 11, and an outer tube 12. The needle seat has a drug flow channel and a protective gas flow channel. Both the inner tube 11 and the outer tube 12 are made of 316L stainless steel. The inner tube 11 and the outer tube 12 are fixedly mounted on the needle seat and are arranged coaxially at intervals on the needle seat. The outlet end of the inner tube 11 extends beyond the outlet end of the outer tube 12, and the distance between the outlet ends of the inner tube 11 and the outer tube 12 is 3mm. An annular airflow channel 13 is formed between the outer wall of the inner tube 11 and the inner wall of the outer tube 12. The inner tube 11 is connected to the drug flow channel on the needle seat. The annular airflow channel 13 is connected to the protective gas flow channel; three spiral partition plates 14 are installed between the outer wall of the outlet end of the inner tube 11 and the inner wall of the outlet end of the outer tube 12. The three spiral partition plates 14 are evenly spaced along the circumference of the inner tube 11, and the three spiral partition plates 14 divide the outlet end of the annular airflow channel 13 into four spiral guide grooves 15. The four spiral guide grooves 15 are evenly spaced along the circumference of the inner tube 11, and the spiral angle of the four spiral guide grooves 15 is 45°; the end face of the outlet end of the inner tube 11 is a slope 16, and the inclination angle of the slope 16 is 30°.

[0061] A filling test was conducted using 2mL ampoules with a nitrogen flow rate of 10L / min for 0.5 seconds. Then, a laser residual oxygen meter was used to detect the oxygen content inside the unsealed ampoules after filling. The average value was calculated after testing 20 ampoules.

[0062] Example 2

[0063] like Figure 3 , Figure 4 As shown, this embodiment provides a pressure-splitting gas outlet needle 2, which is used to deliver nitrogen gas for gas replacement in ampoules after drug liquid filling.

[0064] The pressure-dividing gas outlet needle 2 includes a needle seat and a needle tube 21. The needle seat has a protective gas flow channel, and the needle tube 21 is installed on the needle seat and communicates with the protective gas flow channel. The needle tube 21 is made of 316L stainless steel, with an outer diameter of 3.0 mm and a wall thickness of 0.4 mm. The outlet end of the needle tube 21 is also equipped with a closed conical bottom surface 23 for sealing it, and six gas outlet holes 22 are opened on the circumferential surface of the outlet end of the needle tube 21. The six gas outlet holes 22 are evenly spaced along the circumferential direction of the needle tube 21. The gas outlet holes 22 are elongated flat holes, and the long side of the gas outlet holes 22 is set along the axial direction of the needle tube 21. The short side is set along the circumference of the needle tube 21. The width of the air outlet 22 is 0.3mm and the length of the air outlet 22 is 1.5mm. The outlet direction of the air outlet 22 is inclined downward relative to the radial direction of the needle tube 21, and the inclination angle is 30°. The outlet end of the needle tube 21 is also equipped with a closed conical bottom surface 23 to seal it. The cone angle of the closed conical bottom surface 23 is 120°. The closed conical bottom surface 23 is formed by cold extrusion of the bottom of the needle tube 21 or by machining of solid bar stock. A central air outlet 24 is opened in the center of the conical bottom surface, and the diameter of the central air outlet 24 is 0.5mm.

[0065] Gas displacement tests were conducted on 2mL ampoules after the drug solution was filled. The nitrogen filling pressure was 0.15MPa, the flow rate was 5L / min, and the duration was 0.4 seconds. Then, a high-speed camera was used to observe the liquid level in the ampoule during the gas displacement test. A laser residual oxygen meter was used to detect the residual oxygen in the headspace of the ampoule after sealing. After testing 20 ampoules, the average residual oxygen in the headspace of this batch of ampoules after sealing was calculated.

[0066] Example 3

[0067] Based on the double-layer spiral flow guide needle 1 provided in Example 1 and the pressure-splitting gas outlet needle 2 provided in Example 2, this embodiment provides a method for controlling residual oxygen during the filling process of 2mL ampoules, including the following steps:

[0068] S1. Insert the double-layer spiral guide needle 1 into the ampoule, and position the outlet end of the outer tube 12 on the double-layer spiral guide needle 1 at the junction of the ampoule body and the ampoule neck. Nitrogen gas entering the annular airflow channel 13 is guided by the spiral guide groove 15 to form a spiral airflow, and is ejected from the outlet end of the outer tube 12 in a spiral manner, so that a rotating downward airflow field is formed inside the ampoule, and the air inside the ampoule is discharged from the ampoule mouth, thus performing oxygen removal from the empty ampoule; the flow rate of nitrogen gas through the double-layer spiral guide needle 1 is 12L / min, the gradient decreases to 6L / min, and the duration is 0.6 seconds;

[0069] S2. The double-layer spiral guide needle 1 stops the delivery of nitrogen gas. The medicine is injected into the ampoule through the inner tube 11 on the double-layer spiral guide needle 1. The medicine discharged through the inner tube 11 flows down the wall of the ampoule to fill the medicine. The filling speed is 10mL / s.

[0070] S3. The double-layer spiral guide needle 1 stops the delivery of the liquid medicine and is removed. The pressure-splitting gas outlet needle 2 is then inserted into the ampoule, with the outlet end of the needle tube 21 of the pressure-splitting gas outlet needle 2 aligned with the neck of the ampoule. The gas outlet on the needle tube 21 is positioned 5 mm above the liquid medicine surface. The nitrogen gas entering the needle tube 21 is ejected through the gas outlet 22 and the central gas outlet 24, forming a covering gas flow layer above the liquid medicine surface for headspace displacement. The flow rate of nitrogen gas through the double-layer spiral guide needle 1 is 6 L / min, and the duration is 0.4 seconds.

[0071] S4. The pressure-distributing gas outlet needle 2 stops the delivery of nitrogen and removes the pressure-distributing gas outlet needle 2 from the ampoule to perform a melt seal on the ampoule, thus completing the sealing of the ampoule.

[0072] A high-speed camera was used to observe the liquid level in the ampoules during the gas replacement test after the liquid was filled. A laser residual oxygen meter was used to detect the residual oxygen in the headspace of the ampoules after sealing. After testing 20 ampoules, the average residual oxygen in the headspace of this batch of ampoules after sealing was calculated.

[0073] Comparative Example 1

[0074] This comparative example uses a traditional beveled needle produced on the same filling and sealing equipment for the pre-nitrogen filling, drug filling, and secondary nitrogen filling processes of 2ml ampoules.

[0075] Nitrogen filling (empty bottle replacement): Before filling the medicine, nitrogen gas is introduced into the empty ampoule through the first nitrogen filling needle with a beveled structure. The nitrogen pressure is 0.05-0.40 MPa and the filling time is 0.8-1 second.

[0076] Medicine filling: After nitrogen filling, the medicine is injected into the ampoule through the filling needle.

[0077] Secondary nitrogen filling (headspace displacement): After the medicine is filled, nitrogen gas is injected again into the space above the medicine in the ampoule through a second nitrogen filling needle with a beveled structure (or the same needle). The nitrogen pressure is 0.05-0.40 MPa and the nitrogen filling time is 0.8-1 second.

[0078] Sealing: After nitrogen filling is completed, remove the needle and seal the ampoule by melting.

[0079] A high-speed camera was used to observe the liquid level in the ampoules during the gas replacement test after the liquid was filled. A laser residual oxygen meter was used to detect the residual oxygen in the headspace of the ampoules after sealing. After testing 20 ampoules, the average residual oxygen in the headspace of this batch of ampoules after sealing was calculated.

[0080] The results show that using the double-layer spiral guide needle 1 and the pressure-splitting gas outlet needle 2 can effectively reduce the residual oxygen level in the ampoule. When combined with the residual oxygen control method provided by this invention, the two can not only significantly reduce the residual oxygen level in the ampoule, but also significantly reduce the impact of nitrogen filling on the drug liquid surface during the secondary nitrogen filling process, effectively preventing drug liquid splashing.

[0081] Based on the test results of Examples 1, 2, 3 and Comparative Example 1, the main evaluation indicators include: the liquid level state inside the ampoule during the secondary nitrogen filling process and the average residual oxygen value in the headspace of the ampoule. As can be clearly seen from Table 1, the residual oxygen control method in the drug filling process provided in Example 3 can not only prevent any splashing or significant fluctuations in the liquid level, but also control the residual oxygen content in the headspace of the ampoule after sealing to be less than 0.5%.

[0082] Table 1. Test results of Examples 1, 2, 3 and Comparative Example 1

[0083]

[0084] Those skilled in the art should understand that the above embodiments are merely for illustrating the present invention and are not intended to limit the scope of the invention. Those skilled in the art can make other changes or modifications based on the above disclosure, and these changes or modifications still fall within the scope of the present invention.

Claims

1. A potting needle structure, characterized in that, It includes a double-layer spiral guide needle (1) for conveying protective gas and liquid medicine, and a pressure-dividing outlet needle (2) for the subsequent protective gas. The protective gas entering the double-layer spiral guide needle (1) is spirally delivered, and the protective gas entering the pressure-dividing outlet needle (2) is delivered from its side and bottom.

2. The potting needle structure according to claim 1, characterized in that, The protective gas delivered by the double-layer spiral guide needle (1) is used for gas replacement before filling, and the nitrogen delivered by the pressure-dividing gas outlet needle (2) is used for gas replacement after filling.

3. The potting needle structure according to claim 1 or 2, characterized in that, The double-layer spiral guide needle (1) includes an inner tube (11) and an outer tube (12) arranged coaxially. An annular airflow channel (13) is formed between the outer wall of the inner tube (11) and the inner wall of the outer tube (12). The inner tube (11) is used to transport the liquid medicine, and the annular airflow channel (13) is used to transport the protective gas.

4. The potting needle structure according to claim 3, characterized in that, The annular airflow channel (13) is also equipped with a spiral flow guide structure for guiding the protective gas flow at its outlet end.

5. The potting needle structure according to claim 4, characterized in that, The spiral flow guiding structure includes a spiral partition plate (14) disposed between the outer wall of the inner tube (11) and the inner wall of the outer tube (12). The spiral partition plate (14) divides the outlet end of the annular airflow channel (13) into multiple spiral guide grooves (15).

6. The potting needle structure according to claim 5, characterized in that, There are multiple spiral partition plates (14), and the multiple spiral partition plates (14) are evenly spaced along the circumferential direction of the annular airflow channel (13).

7. The potting needle structure according to claim 5, characterized in that, The number of spiral guide grooves (15) is 3 to 6.

8. The potting needle structure according to claim 5, characterized in that, The helix angle of the spiral guide groove (15) is 30° to 60°.

9. The potting needle structure according to claim 3, characterized in that, The outlet end of the inner tube (11) extends beyond the outlet end of the outer tube (12).

10. The potting needle structure according to claim 9, characterized in that, The length of the outlet end of the inner tube (11) extending beyond the outlet end of the outer tube (12) is 2 to 5 mm.

11. The potting needle structure according to claim 3, characterized in that, The outlet end of the inner tube (11) is a slope (16), and the inclination angle of the slope (16) is 15° to 45°.

12. The potting needle structure according to claim 1, characterized in that, The pressure-dividing air outlet needle (2) includes a needle tube (21), and multiple air outlet holes (22) are arranged at intervals along the circumferential direction on the side wall of the outlet end of the needle tube (21).

13. The potting needle structure according to claim 12, characterized in that, The number of air outlets (22) is 4 to 8.

14. The potting needle structure according to claim 12, characterized in that, The multiple air outlets (22) are evenly spaced along the circumference of the needle tube (21).

15. The potting needle structure according to claim 12, characterized in that, The air outlet (22) is a long, flat hole, with the long side of the air outlet (22) arranged along the axial direction of the needle tube (21).

16. The potting needle structure according to claim 15, characterized in that, The air outlet (22) has a width of 0.2-0.5 mm and a length of 1.0-2.0 mm.

17. The potting needle structure according to claim 12, characterized in that, The outlet end of the needle (21) is also equipped with a closed conical bottom surface (23) to seal it, and a central air outlet (24) is provided in the center of the conical bottom surface.

18. The potting needle structure according to claim 17, characterized in that, The cone angle of the closed conical bottom surface (23) is 100° to 150°.

19. The potting needle structure according to claim 17, characterized in that, The outlet direction of the central air outlet (24) is inclined downward relative to the radial direction of the needle tube (21), and the inclination angle is 15° to 45°.

20. A method for controlling residual oxygen during the drug filling process based on the filling needle structure according to any one of claims 1 to 19, characterized in that, Includes the following steps: S1. Insert the double-layer spiral guide needle (1) into the ampoule and make the protective gas delivered from the double-layer spiral guide needle (1) correspond to the junction of the ampoule body and the ampoule neck. After the protective gas is delivered through the double-layer spiral guide needle (1), it forms a spiral airflow that sprays downwards and forms a rotating downward airflow field inside the ampoule, which discharges the air from the ampoule mouth. S2. The double-layer spiral guide needle (1) stops the delivery of protective gas, and the medicine is injected into the ampoule through the double-layer spiral guide needle (1); S3. Remove the double-layer spiral guide needle (1) and insert the pressure-splitting gas outlet needle (2) into the neck of the ampoule. Protect the gas from its side and bottom to form a covering gas flow layer above the liquid surface. S4. The pressure-distributing gas outlet needle (2) stops the delivery of protective gas and removes the pressure-distributing gas outlet needle (2) from the ampoule to seal the ampoule.

21. The residual oxygen control method according to claim 20, characterized in that, The flow rate of the protective gas through the double-layer spiral guide needle (1) is 5-15 L / min, and the duration is 0.3-0.8 seconds.

22. The residual oxygen control method according to claim 21, characterized in that, The flow rate of the protective gas through the double-layer spiral guide needle (1) is controlled by gradient: the flow rate of the protective gas is 8-12 L / min in the initial 0.1 seconds, and then the flow rate of the protective gas is 5-8 L / min.

23. The residual oxygen control method according to claim 20, characterized in that, The flow rate of the protective gas through the pressure-dividing outlet needle (2) is 3-8 L / min, and the duration is 0.2-0.5 seconds.

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