Vacuum plugging method for pre-filled glass injector

Abstract

The invention provides a vacuum plugging method for a pre-filled glass injector, and belongs to the technical field of pre-filled injectors. According to the invention, an efficient and continuous process flow is constructed around the characteristics of equipment, specifically, an ozone medium is firstly adopted to sterilize a sealing bin, and then low-concentration ozone is adopted to construct a positive pressure environment, so that the reliability of a sterile environment is ensured; according to the process, the pneumatic rotating disc rotates between two stations, loading and unloading are carried out through the mechanical arm, and clamping and fixing are carried out through the clamp; the filling unit is driven by a first air cylinder to do feeding motion, a local sealing environment is constructed through a rubber ring, and then liquid medicine is injected into an injector through negative pressure. The filled injector can be subjected to ultrasonic defoaming and then arrives at a plug pressing station, a sealed environment is formed by the buckling cover, and the plug pressing action is completed. According to the method disclosed by the invention, the advantages of equipment are fully exerted, continuous completion of double procedures is realized, the reliability of a sterile environment is ensured, and the production efficiency and the yield are remarkably improved.

Description

Technical Field

[0001] The invention relates to the technical field of prefilled syringes, in particular to a vacuum stoppering method for prefilled glass syringes. Background Art

[0002] Prefilled syringes, also known as pre-filled syringes, are widely used as a drug delivery system for injectable drugs in the packaging of high-value products such as biological products, biochemical products, antithrombotic drugs, and beauty products. By 2023, the global prefilled syringe market will reach US$3.9 billion. Prefilled syringes consist of a glass syringe, a halogenated butyl rubber piston, a push rod and / or an injection needle, and a needle cap. They are mainly used for packaging and storage of small-volume injections and for injection or ophthalmic, otological, orthopedic and other surgical flushing. At present, they are increasingly used in the fields of vaccines, antithrombotic drugs, therapeutic albumin and interferon.

[0003] Good sealing is a necessary condition to ensure the safety and effectiveness of prefilled syringe products, and leakage problems will lead to serious product defects. Leakage may cause product losses such as evaporation of the perfusate and liquid seepage, and may also cause contamination of the filling components and loss of sterility, and may also cause contact injuries to product handling personnel. For prefilled syringes, leakage usually occurs in component cracks, component pinholes, seal defects, etc. Therefore, the sealing verification of the product should run through the processes of packaging development verification, routine production, and monitoring of marketed products, covering the entire life cycle of the product. When conducting sealing verification, the appropriate verification method can be comprehensively selected based on the syringe material, structure, and maximum allowable leakage. In addition, attention should also be paid to the lateral, axial and positive pressures on the prefilled syringe, as well as the possibility of leakage at the piston or sealing ring under negative pressure conditions.

[0004] The filling process is one of the core processes in the production process of prefilled syringes. During the filling process, attention should be paid to the filling speed, filling volume, piston assembly method, bubble elimination, etc. Prefilled syringes usually reserve a small amount of air in the syringe filled with the liquid medicine, and inject directly during clinical use without exhausting bubbles. Its main purpose is: ① During clinical use, a small amount of liquid medicine will remain in the syringe needle and syringe. The reserved bubbles can reduce the residual liquid medicine during discharge and avoid waste of liquid medicine; ② A small amount of bubbles is reserved in the syringe. When the liquid medicine is fully injected, the bubbles continue to be injected. After the needle is removed, the inertia brings out the air, which can effectively reduce the phenomenon of liquid medicine back seepage. At the same time, it also prevents the stimulation of the tissue by the drug leakage after the needle is removed, and reduces the pain of the patient's local injection site. In the prior art, conventional filling machines need to be improved in terms of sterility assurance, and they cannot continuously complete the two steps of filling and plugging. To address this problem, the applicant has designed a completely new structure of stoppering and filling equipment, which is significantly different from existing products in terms of structure and working principle. In this case, how to design the process in a targeted manner around the characteristics of the equipment to maximize the improvement of production efficiency and yield rate is a technical problem that still needs to be solved. Summary of the invention

[0005] The technical problem to be solved by the present invention is: how to design the process in a targeted manner around the characteristics of the equipment to maximize the improvement of production efficiency and yield rate.

[0006] In order to achieve the above technical objectives, the present invention adopts the following technical solutions: A vacuum stoppering method for prefilled glass syringes comprises the following steps: 1) Use an ozone generator to input ozone into the sealed chamber through the ozone input pipe for 60 to 120 minutes, then keep the sealed chamber in a sealed state, and use a booster pipe to increase the air pressure in the sealed chamber to 1.01 to 1.02 atmospheres; 2) The syringe to be filled is loaded onto the fixture by the manipulator in the sealing chamber, and the fixture is clamped. After the manipulator is reset, air is supplied to the pneumatic turntable through the first compressed air pipe to rotate the pneumatic turntable until the fixture reaches the bottom of the filling unit; 3) Supplying air to the first cylinder through the second compressed air pipe causes the first support plate and the cross frame located at the free end of the first cylinder to move downward along the first guide rod until the filling tube of the filling unit is inserted into the cavity of the syringe, and the rubber ring abuts against the filling port of the syringe, and then the pressure is reduced through the negative pressure tube, so that the drug solution is filled into the syringe through the drug solution tube; 4) The first cylinder is reset, and then air is supplied to the pneumatic turntable through the first compressed air pipe, causing the pneumatic turntable to rotate until the fixture reaches the bottom of the second cylinder; 5) Supplying air to the second cylinder through the third compressed air pipe, so that the second support plate located at the free end of the second cylinder moves downward along the second guide rod until the pressing cover abuts against the filling port of the syringe and is pressed by the pressing head; 6) The second cylinder is reset, the fixture is released, and then the robot unloads the inserted syringe from the fixture.

[0007] Preferably, the following step 7 is also included): the manipulator is reset, and pressurization at the boost pipe is stopped until the sealed chamber returns to normal pressure, and then the sealed chamber is opened.

[0008] Preferably, a finished product area and a material area are provided in the sealed bin, the syringes to be filled are located in the material area, and the syringes that have been filled and stoppered are located in the finished product area.

[0009] Preferably, in step 1), during the 60-120 min period, the ozone concentration in the sealed chamber is 50-70 mg / m 3 .

[0010] As a preferred embodiment, during the execution of step 2) to step 6), the sealed chamber still contains 10-20 mg / m 3 ozone content.

[0011] Preferably, in step 3), the drug solution is poured into the syringe through the holes at the lower part of the drug solution tube and the side wall of the filling tube, and the bottom end of the filling tube is closed by a conical plug, and the conical surface of the conical plug is located inside the hole.

[0012] Preferably, the clamps are arranged in rows, and each row of clamps is fixedly connected to a base, and the base is fixedly connected to the disk surface of the pneumatic turntable.

[0013] Preferably, in step 3), the process of injecting the drug solution into the syringe through the drug solution tube includes three stages, wherein the output speed of the drug solution in the first stage is 5-8 mL / s, the output speed of the drug solution in the second stage is 2-3 mL / s, and the output speed of the drug solution in the third stage is 0.5-1 mL / s.

[0014] Preferably, in step 3), after the filling process is completed, an ultrasonic transducer located below the pneumatic turntable constructs an ultrasonic oscillation environment of 25-35 kHz, which is maintained for 1-2 seconds, and then step 4) is performed.

[0015] Preferably, the medicine liquid pipe is connected to the medicine liquid tank located outside the sealed chamber through a hose, a solenoid valve is provided on the hose, and the medicine liquid in the medicine liquid tank is sterilized by heating or filtering in advance.

[0016] The present invention provides a vacuum stoppering method for prefilled glass syringes. This technical solution constructs an efficient and continuous process flow around the characteristics of the equipment. Specifically, the present invention first uses ozone medium to sterilize the sealing chamber, and then uses low-concentration ozone to build a positive pressure environment to ensure the reliability of the sterile environment; in terms of process, the present invention rotates a pneumatic turntable between two stations, uses a manipulator to load and unload materials, and is clamped and fixed by a fixture; the filling unit is driven by the first cylinder to perform feeding movement, and a local sealing environment is constructed using a rubber ring, and then the liquid medicine is filled into the syringe using negative pressure; the filled syringe can be ultrasonically defoamed, and then arrive at the stoppering station, where a sealing environment is formed by a buckling cover, and the stoppering action is completed. The method of the present invention gives full play to the advantages of the equipment, not only realizing the continuous completion of the two processes, but also ensuring the reliability of the sterile environment, and significantly improving production efficiency and yield rate. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 is an overall diagram of the equipment used in the method of the present invention; Figure 2 is a partial diagram of the apparatus used in the method of the present invention; Figure 3 is a structural diagram of the pneumatic turntable and the clamp in the method of the present invention; Figure 4 It is a structural diagram of the pneumatic turntable and its air circuit in the method of the present invention; Figure 5 It is a first structural diagram of the first cylinder, the filling unit and other components in the method of the present invention; Figure 6 It is a second structural diagram of the first cylinder, the filling unit and other components in the method of the present invention; Figure 7 is an exploded diagram of a filling unit in the method of the present invention; Figure 8 It is the first structural diagram of the second cylinder, the pressing cover and other components in the method of the present invention; Fig. 9 It is a second structural diagram of the second cylinder, the pressing cover and other components in the method of the present invention; In the figure: DETAILED DESCRIPTION

[0018] The specific embodiments of the present invention will be described in detail below. In order to avoid too much unnecessary details, the well-known structures or functions will not be described in detail in the following examples. The approximate language used in the following examples can be used for quantitative expression, indicating that the quantity can be allowed to have a certain change without changing the basic function. Unless otherwise defined, the technical and scientific terms used in the following examples have the same meaning as those generally understood by those skilled in the art to which the present invention belongs.

[0019] Example 1 See also Figure 1 to Figure 9 , a vacuum stoppering method for a prefilled glass syringe, comprising the following steps: 1) Use the ozone generator 2 to input ozone into the sealed chamber 1 through the ozone input pipe 3 for 60 to 120 minutes, then keep the sealed chamber 1 in a sealed state, and use the booster pipe 4 to increase the air pressure in the sealed chamber 1 to 1.01 to 1.02 atmospheres; 2) The syringe to be filled is loaded onto the clamp 6 by the manipulator in the sealing chamber 1, and the clamp 6 clamps it. After the manipulator is reset, air is supplied to the pneumatic turntable 5 through the first compressed air pipe 7, so that the pneumatic turntable 5 rotates until the clamp 6 reaches the bottom of the filling unit 13; 3) Air is supplied to the first cylinder 9 through the second compressed air pipe 8, so that the first support plate 10 and the cross frame 12 located at the free end of the first cylinder 9 move downward along the first guide rod 11 until the filling tube 15 of the filling unit 13 is inserted into the cavity of the syringe, and at the same time, the rubber ring 14 abuts against the filling port of the syringe, and then the pressure is reduced through the negative pressure pipe 16, so that the drug solution is filled into the syringe through the drug solution pipe 17; 4) The first air cylinder 9 is reset, and then air is supplied to the pneumatic turntable 5 through the first compressed air pipe 7, so that the pneumatic turntable 5 rotates until the clamp 6 reaches below the second air cylinder 19; 5) Supplying air to the second air cylinder 19 through the third compressed air pipe 18 causes the second support plate 20 located at the free end of the second air cylinder 19 to move downward along the second guide rod 21 until the pressing cover 22 abuts against the filling port of the syringe and is plugged by the pressing head 23; 6) The second cylinder 19 is reset, the fixture 6 is released, and then the robot unloads the syringe that has been plugged from the fixture 6.

[0020] Example 2 See also Figure 1 to Figure 9 , a vacuum stoppering method for a prefilled glass syringe, comprising the following steps: 1) Use the ozone generator 2 to input ozone into the sealed chamber 1 through the ozone input pipe 3 for 60 to 120 minutes, then keep the sealed chamber 1 in a sealed state, and use the booster pipe 4 to increase the air pressure in the sealed chamber 1 to 1.01 to 1.02 atmospheres; 2) The syringe to be filled is loaded onto the clamp 6 by the manipulator in the sealing chamber 1, and the clamp 6 clamps it. After the manipulator is reset, air is supplied to the pneumatic turntable 5 through the first compressed air pipe 7, so that the pneumatic turntable 5 rotates until the clamp 6 reaches the bottom of the filling unit 13; 3) Air is supplied to the first cylinder 9 through the second compressed air pipe 8, so that the first support plate 10 and the cross frame 12 located at the free end of the first cylinder 9 move downward along the first guide rod 11 until the filling tube 15 of the filling unit 13 is inserted into the cavity of the syringe, and at the same time, the rubber ring 14 abuts against the filling port of the syringe, and then the pressure is reduced through the negative pressure pipe 16, so that the drug solution is filled into the syringe through the drug solution pipe 17; 4) The first air cylinder 9 is reset, and then air is supplied to the pneumatic turntable 5 through the first compressed air pipe 7, so that the pneumatic turntable 5 rotates until the clamp 6 reaches below the second air cylinder 19; 5) Supplying air to the second air cylinder 19 through the third compressed air pipe 18 causes the second support plate 20 located at the free end of the second air cylinder 19 to move downward along the second guide rod 21 until the pressing cover 22 abuts against the filling port of the syringe and is plugged by the pressing head 23; 6) The second cylinder 19 is reset, the fixture 6 is released, and then the manipulator unloads the syringe that has been plugged from the fixture 6; 7 The manipulator is reset, and the pressurization at the boost pipe 4 is stopped until the pressure in the sealed chamber 1 returns to normal, and then the sealed chamber 1 is opened.

[0021] The sealed chamber 1 is provided with a finished product area and a material area, the syringes to be filled are located in the material area, and the syringes that have been filled and plugged are located in the finished product area. In step 1), during the 60-120 min maintenance, the ozone concentration in the sealed chamber 1 is 50-70 mg / m 3 During the execution of steps 2) to 6), the sealed chamber 1 still contains 10~20 mg / m 3ozone content. In step 3), the medicine liquid is poured into the syringe through the holes at the lower part of the side wall of the medicine liquid tube 17 and the filling tube 15, and the bottom end of the filling tube 15 is closed by a conical plug, and the conical surface of the conical plug is located on the inner side of the hole. The clamps 6 are arranged in rows, and each row of clamps 6 is fixedly connected to a base, and the base is fixedly connected to the disk surface of the pneumatic turntable 5. In step 3), the process of pouring the medicine liquid into the syringe through the medicine liquid tube 17 includes three stages. The output speed of the medicine liquid in the first stage is 5~8mL / s, the output speed of the medicine liquid in the second stage is 2~3mL / s, and the output speed of the medicine liquid in the third stage is 0.5~1mL / s. In step 3), after the filling process is completed, an ultrasonic oscillation environment of 25~35KHz is constructed by the ultrasonic transducer located below the pneumatic turntable 5, maintained for 1~2s, and then step 4) is executed. The drug liquid pipe 17 is connected to the drug liquid tank located outside the sealed chamber 1 through a hose, and a solenoid valve is provided on the hose. The drug liquid in the drug liquid tank is sterilized by heating or filtering in advance.

[0022] The embodiments of the present invention are described in detail above, but the contents are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the scope of the present invention shall be included in the protection scope of the present invention.

Claims

1. A vacuum stoppering method for prefilled glass syringes, characterized in that The following steps are involved: 1) Use an ozone generator to input ozone into the sealed chamber through the ozone input pipe for 60 to 120 minutes, then keep the sealed chamber in a sealed state, and use a booster pipe to increase the air pressure in the sealed chamber to 1.01 to 1.02 atmospheres; 2) The syringe to be filled is loaded onto the fixture by the manipulator in the sealing chamber, and the fixture is clamped. After the manipulator is reset, air is supplied to the pneumatic turntable through the first compressed air pipe to rotate the pneumatic turntable until the fixture reaches the bottom of the filling unit; 3) Supplying air to the first cylinder through the second compressed air pipe causes the first support plate and the cross frame located at the free end of the first cylinder to move downward along the first guide rod until the filling tube of the filling unit is inserted into the cavity of the syringe, and the rubber ring abuts against the filling port of the syringe, and then the pressure is reduced through the negative pressure tube, so that the drug solution is filled into the syringe through the drug solution tube; 4) The first cylinder is reset, and then air is supplied to the pneumatic turntable through the first compressed air pipe, causing the pneumatic turntable to rotate until the fixture reaches the bottom of the second cylinder; 5) Supplying air to the second cylinder through the third compressed air pipe, so that the second support plate located at the free end of the second cylinder moves downward along the second guide rod until the pressing cover abuts against the filling port of the syringe and is pressed by the pressing head; 6) The second cylinder is reset, the fixture is released, and then the robot unloads the inserted syringe from the fixture.

2. The vacuum stoppering method for a prefilled glass syringe according to claim 1, characterized in that: The process also includes the following steps 7): the manipulator is reset, pressurization at the boost pipe is stopped until the sealed chamber returns to normal pressure, and then the sealed chamber is opened.

3. The vacuum stoppering method for a prefilled glass syringe according to claim 1, characterized in that: A finished product area and a material area are provided in the sealed bin. The syringes to be filled are located in the material area, and the syringes that have been filled and stoppered are located in the finished product area.

4. The vacuum stoppering method for a prefilled glass syringe according to claim 1, characterized in that: In step 1), during the 60-120 min period, the ozone concentration in the sealed chamber is 50-70 mg / m 3 .

5. The vacuum stoppering method for prefilled glass syringes according to claim 1, characterized in that: During the execution of steps 2) to 6), the sealed chamber still contains 10~20 mg / m 3 ozone content.

6. The vacuum stoppering method for prefilled glass syringes according to claim 1, characterized in that: In step 3), the drug solution is poured into the syringe through the holes in the lower part of the drug solution tube and the side wall of the filling tube, and the bottom end of the filling tube is closed by a conical plug, and the conical surface of the conical plug is located inside the hole.

7. The vacuum stoppering method for a prefilled glass syringe according to claim 1, characterized in that: The clamps are arranged in rows, and each row of clamps is fixedly connected to a base, and the base is fixedly connected to the disk surface of the pneumatic turntable.

8. The vacuum stoppering method for prefilled glass syringes according to claim 1, characterized in that: In step 3), the process of injecting the drug solution into the syringe through the drug solution tube includes three stages. The output speed of the drug solution in the first stage is 5-8 mL / s, the output speed of the drug solution in the second stage is 2-3 mL / s, and the output speed of the drug solution in the third stage is 0.5-1 mL / s.

9. The vacuum stoppering method for a prefilled glass syringe according to claim 1, characterized in that: In step 3), after the filling process is completed, an ultrasonic transducer located below the pneumatic turntable creates an ultrasonic oscillation environment of 25-35 kHz, which is maintained for 1-2 seconds, and then step 4) is performed.

10. The vacuum stoppering method for prefilled glass syringes according to claim 1, characterized in that: The liquid medicine pipe is connected to the liquid medicine tank located outside the sealed chamber through a hose, and a solenoid valve is arranged on the hose. The liquid medicine in the liquid medicine tank is sterilized by heating or filtering in advance.

Images