A double butterfly valve sterile drug transfer system and sterile drug transfer method

Abstract

The present invention discloses a double butterfly valve aseptic drug transfer system and a aseptic drug transfer method, which relate to the field of pharmaceutical technology. The present invention comprises a reversible drug storage tank, an active butterfly valve, a passive butterfly valve, a powder storage tank and a sterile liquid medicine storage bag. The discharge port of the reversible drug storage tank is connected to the active butterfly valve via a first connecting piece, the active butterfly valve is connected to the passive butterfly valve via a second connecting piece, the passive butterfly valve is connected to the feed port of the powder storage tank via a third connecting piece, the discharge port of the powder storage tank is provided with a diaphragm valve 1, and the discharge port of the powder storage tank is connected to the sterile liquid medicine storage bag. The present invention adopts a double butterfly valve design to establish an aseptic connection between the reversible drug storage tank and the powder storage tank, and the clamp connection has strong reliability, simple structure, low operation complexity, strong versatility, high flexibility and low cost.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology, in particular to a double butterfly valve aseptic drug transfer system and a aseptic drug transfer method. Background Art

[0002] In the pharmaceutical industry, existing aseptic production technologies enable the safe transfer of sterile drugs from one sterile container to another in a non-sterile background environment (such as a Grade C environment). Commonly used closed aseptic connection technologies in the industry include SUS (Single Use System), SART system, AB valve system, and vacuum suction system.

[0003] Both the SUS system and the SART system are disposable systems, which not only have high material costs but also increase processing costs. In addition, the research on extractables and leachables (E&L) of disposable systems is relatively complex, and there are certain quality risks and compliance challenges. They are only suitable for the closed transfer of sterile liquid medicines. The AB valve system is designed with specific dimensions and is highly complex to operate. In the case of large-scale production, the risk of errors also increases accordingly. It is also expensive and costly, and is only suitable for the closed transfer of sterile powders. The vacuum suction system is designed with many pipelines and valve connections and a complex structure. During the powder discharging process, a large amount of adhesion occurs at the pipes and valves, resulting in large discharge residues and low product yield. It is only suitable for the closed transfer of sterile powders.

[0004] Therefore, the closed transfer system of sterile drugs in the prior art has the defects of low versatility, high operation complexity, high cost, and large discharge residue. Based on this, a double butterfly valve sterile drug transfer system and a sterile drug transfer method are now provided. Summary of the Invention

[0005] The present invention is intended to solve the technical problems of low versatility, high operational complexity, high cost, and large discharge residue in the closed transfer system of sterile drugs in the prior art. The purpose is to provide a double butterfly valve sterile drug transfer system and a sterile drug transfer method. A double butterfly valve design is adopted to establish a sterile connection between a reversible drug storage tank and a powder storage tank. The clamp is used as a connecting part to ensure the connection reliability. The structure is simple, the operational complexity is low, and it can be applied to the sterile transfer of powders and liquids at the same time. It has strong versatility, high flexibility, and low cost.

[0006] The present invention is achieved through the following technical solutions:

[0007] The first object of the present invention is to provide a double butterfly valve sterile drug transfer system, comprising a reversible drug storage tank, an active butterfly valve, a passive butterfly valve, a powder storage tank and a sterile liquid drug storage bag;

[0008] The discharge port of the reversible drug storage tank is connected to the active butterfly valve via a first connecting piece, the active butterfly valve is connected to the passive butterfly valve via a second connecting piece, and the passive butterfly valve is connected to the feed port of the powder storage tank via a third connecting piece;

[0009] The discharge port of the powder storage tank is provided with a diaphragm valve 1, and the discharge port of the powder storage tank is connected to the sterile liquid medicine storage bag.

[0010] Furthermore, the first connecting member is a clamp.

[0011] Furthermore, the second connecting member includes a first clamp, a connector and a second clamp, the first clamp clamps the active butterfly valve and the connector together, and the second clamp clamps the connector and the passive butterfly valve together.

[0012] Furthermore, the third connecting member is a clamp.

[0013] Furthermore, the discharge port of the powder storage tank is connected to the sterile liquid medicine storage bag through a sterile liquid medicine transfer pipeline.

[0014] Furthermore, the discharge port of the powder storage tank is also connected to a steam discharge pipeline.

[0015] Furthermore, a second diaphragm valve is provided at the inlet end of the steam exhaust pipeline.

[0016] Furthermore, the discharge port of the powder storage tank is connected to the inlet of a three-way joint, and the two outlets of the three-way joint are respectively connected to the sterile liquid transfer pipeline and the steam exhaust pipeline.

[0017] A second object of the present invention is to provide a method for aseptic drug transfer, comprising the following steps:

[0018] Open the active and passive butterfly valves, and introduce steam into the system so that the steam can flow between the reversible drug storage tank and the sterile drug storage bag. Sterilize the system with wet heat at 120-130°C for 15-30 minutes. After steam sterilization is complete, keep the system in a slightly positive pressure state.

[0019] Close the active butterfly valve and the passive butterfly valve, and the sterile drug is delivered to the reversible drug storage tank;

[0020] When the transferred drug is a sterile liquid, open the active butterfly valve, passive butterfly valve and diaphragm valve 1 in sequence, and introduce clean compressed air into the reversible drug storage tank with a pressure of ≤0.20MPa. The sterile liquid is transferred to the sterile liquid storage bag through the powder storage tank and the sterile liquid transfer pipeline in sequence. After the transfer is completed, close the diaphragm valve 1, passive butterfly valve and active butterfly valve;

[0021] When the transferred drug is sterile powder, keep the diaphragm valve closed, open the active butterfly valve and the passive butterfly valve in sequence, and transfer the sterile powder to the powder storage tank. After the transfer is completed, close the passive butterfly valve and the active butterfly valve.

[0022] Furthermore, during steam sterilization, the second diaphragm valve is opened to discharge steam from the steam discharge line.

[0023] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0024] 1. The transfer device of the present invention adopts a clamp as a connecting piece, and connects the active butterfly valve and the passive butterfly valve, as well as the active butterfly valve and the discharge port, and the passive butterfly valve and the powder storage tank through the clamp. Since the clamp has a strong clamping force and good sealing performance, the connection reliability is guaranteed, and the structure is simple and the operation complexity is low.

[0025] 2. The double butterfly valve design of the present invention establishes a sterile connection between the reversible drug storage tank and the powder storage tank, thereby avoiding contamination by human operation and environmental microorganisms.

[0026] 3. The powder storage tank of the present invention is used as a storage tank when transferring powder and as a transfer pipeline when transferring liquid medicine. It is also suitable for the aseptic transfer of powders and liquids. It has strong versatility and high flexibility, reduces dependence on specific types of transfer systems, enhances the efficiency and reliability of aseptic transfer, and reduces production costs. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions of the exemplary embodiments of the present invention, the following briefly introduces the drawings required for use in the examples. It should be understood that the following drawings only illustrate certain embodiments of the present invention and should not be considered as limiting the scope. A person of ordinary skill in the art can also derive other relevant drawings based on these drawings without inventive effort. In the drawings:

[0028] Figure 1 Schematic diagram of the structure of the transfer system of the present invention;

[0029] Figure 2 This is a schematic diagram of the connection structure between the second connecting piece and the powder storage tank of the present invention;

[0030] Figure 3 for Figure 2 Middle AA section view;

[0031] Figure 4 Schematic diagram of the structure of the second connecting member.

[0032] Markings and corresponding parts names in the accompanying drawings:

[0033] 1-reversible drug storage tank, 101-discharge port, 2-first connecting piece, 3-active butterfly valve, 4-second connecting piece, 401-first clamp, 402-connector, 403-second clamp, 5-passive butterfly valve, 6-third connecting piece, 7-powder storage tank, 8-diaphragm valve 1, 9-tee connector, 10-sterile drug solution transfer pipeline, 11-sterile drug solution storage bag, 12-diaphragm valve 2, 13-steam discharge pipeline. DETAILED DESCRIPTION

[0034] In order to make the objectives, technical solutions and advantages of the present invention more clearly understood, the technical solutions in the embodiments of the present invention are clearly and completely described below in conjunction with the embodiments and drawings. Obviously, the schematic implementation methods of the present invention and their descriptions are only used to explain the present invention and are not intended to limit the present invention.

[0035] The following describes, in detail, embodiments of a double butterfly valve sterile drug transfer system and sterile drug transfer method according to the present invention, with appropriate reference to the accompanying drawings. However, unnecessary detailed descriptions may be omitted. For example, detailed descriptions of well-known matters and repetitive descriptions may be omitted. This is done to avoid unnecessary redundancy and to facilitate understanding by those skilled in the art.

[0036] The "ranges" disclosed herein are defined in terms of lower and upper limits. A given range is defined by selecting a lower limit and an upper limit, and the selected lower and upper limits define the boundaries of the particular range. Unless otherwise specified, all embodiments and alternative embodiments of this application may be combined to form new technical solutions.

[0037] Unless otherwise specified, all technical features and optional technical features of this application can be combined with each other to form a new technical solution.

[0038] Unless otherwise specified, the terms "include" and "comprising" used in this application may be open-ended or closed-ended. For example, "include" and "comprising" may mean that other substances not listed may also be included or that only the listed substances are included.

[0039] Unless otherwise specified, all steps of the present application can be performed sequentially or randomly, preferably sequentially.

[0040] The technical solution of the present invention is further described in detail below with reference to the embodiments.

[0041] It should be noted that the experimental methods used in the examples are conventional methods unless otherwise specified. The materials, reagents, methods and instruments used are conventional materials, reagents, methods and instruments in the art, unless otherwise specified, and can be obtained from commercial channels by those skilled in the art.

[0042] Example 1

[0043] A double butterfly valve sterile drug transfer system comprises a reversible drug storage tank 1, an active butterfly valve 3, a passive butterfly valve 5, a powder storage tank 7 and a sterile drug liquid storage bag 11.

[0044] The reversible drug storage tank 1 has a discharge port 101, which is arranged at the upper part of the reversible drug storage tank 1. The discharge port 101 is connected to the active butterfly valve 3 through a first connecting member 2. Specifically, the first connecting member 2 is a clamp, and the connection between the active butterfly valve 3 and the discharge port 101 of the reversible drug storage tank 1 is realized through the first connecting member 2.

[0045] The active butterfly valve 3 is connected to the passive butterfly valve 5 through a second connecting member 4. Specifically, the second connecting member 4 includes a first clamp 401, a connecting head 402 and a second clamp 403. The first clamp 401 clamps the active butterfly valve 3 and the connecting head 402 together, and the second clamp 403 clamps the connecting head 402 and the passive butterfly valve 5 together. The connection between the active butterfly valve 3 and the passive butterfly valve 5 is achieved through the second connecting member 4.

[0046] The passive butterfly valve 5 is connected to the feed port of the powder storage tank 7 via a third connecting piece 6 . Specifically, the third connecting piece 6 is a clamp, and the connection between the passive butterfly valve 5 and the feed port of the powder storage tank 7 is achieved via the third connecting piece 6 .

[0047] The discharge port of the powder storage tank 7 is provided with a diaphragm valve 18, which is connected to a three-way joint 9 through a clamp. The three-way joint 9 adopts a disposable three-way connecting pipe. The two outlets of the three-way joint 9 are respectively connected to a sterile liquid transfer pipeline 10 and a steam discharge pipeline 13; the sterile liquid transfer pipeline 10 is connected to a sterile liquid storage bag 11 for transferring the sterile liquid into the sterile liquid storage bag 11; the inlet end of the steam discharge pipeline 13 is provided with a diaphragm valve 2 12, and steam is discharged from the steam discharge pipeline 13 during sterilization to ensure the sterilization effect of the system.

[0048] When the transfer system of the present invention is in use, the active butterfly valve 3, the passive butterfly valve 5 and the diaphragm valve 1 8 must first be opened, and steam is introduced into the system so that the steam can flow between the reversible drug storage tank 1 and the sterile liquid storage bag 11, and the entire system is steam sterilized. In addition, the diaphragm valve 2 12 also needs to be opened for online sterilization and steam discharge.

[0049] When the transferred drug is liquid, the active butterfly valve 3, the passive butterfly valve 5 and the diaphragm valve 1 8 are opened, the diaphragm valve 2 12 is closed, and the powder storage tank 7 acts as a transfer pipeline. The liquid is transferred to the sterile liquid storage bag 11 through the powder storage tank 7 and the sterile liquid transfer pipeline 10; when the transferred drug is powder, the active butterfly valve 3 and the passive butterfly valve 5 are opened, the diaphragm valve 1 8 and the diaphragm valve 2 12 are closed, and the bottom of the powder storage tank 7 is sealed to prevent the powder in the tank from being contaminated, and the powder is directly transferred to the powder storage tank 7.

[0050] The transfer device of the present invention adopts a clamp as a connecting piece, and connects the active butterfly valve 3 and the passive butterfly valve 5, as well as the active butterfly valve 3 and the discharge port 101, and the passive butterfly valve 5 and the powder storage tank 7 together through the clamp. Since the clamp has a strong clamping force and good sealing performance, the connection reliability is guaranteed, and the structure is simple and the operation complexity is low; at the same time, the double butterfly valve design of the present invention establishes a sterile connection between the flippable drug storage tank 1 and the powder storage tank 7, thereby avoiding contamination by human operation and environmental microorganisms; in addition, the powder storage tank 7 of the present invention is used as a storage tank when transferring powder, and as a transfer pipeline when transferring liquid medicine. It is suitable for the aseptic transfer of powder and liquid, has strong versatility and high flexibility, reduces dependence on a specific type of transfer system, enhances the efficiency and reliability of aseptic transfer, and reduces production costs.

[0051] Example 2

[0052] Based on the transfer system of Example 1, this embodiment provides a method for transferring a sterile liquid medicine, comprising the following steps:

[0053] (1) Before production, check the integrity and sealing of the system connection to ensure that the entire system forms a closed sterile channel when connected. Then open the active butterfly valve 3 and the passive butterfly valve 5 switches and perform an online leak test on the system to ensure the integrity of the system connection.

[0054] (2) After the leak test is passed, the active butterfly valve 3 and the passive butterfly valve 5 are kept open, and steam is introduced into the system so that pure steam can flow between the reversible drug storage tank 1 and the sterile drug storage bag 11. The entire system is sterilized online with moist heat (121°C, 30 minutes). After the sterilization is completed, the system maintains a slightly positive pressure state against the background environment.

[0055] (3) The active butterfly valve 3 and the passive butterfly valve 5 are closed, and 20 kg of sterile liquid medicine prepared by the aseptic production process is transported and stored in the reversible medicine storage tank 1.

[0056] (4) Open the active butterfly valve 3, the passive butterfly valve 5 and the diaphragm valve 8 in sequence, and introduce clean compressed air into the reversible drug storage tank 1 with a pressure of ≤0.20 MPa. The reversible drug storage tank 1 is turned over to discharge the material, and the sterile drug solution is transferred to the sterile drug solution storage bag 11 along the closed sterile channel. After observing the transfer of the sterile drug solution through the sight glass, close the diaphragm valve 8, the passive butterfly valve 5 and the active butterfly valve 3.

[0057] The sterile liquid medicine storage bag 11 of this embodiment receives 19.5 kg of liquid medicine, and the liquid medicine yield is 97.5%.

[0058] Example 3

[0059] Based on the transfer system of Example 1, this embodiment provides a sterile powder transfer method, comprising the following steps:

[0060] (1) Before production, check the integrity and sealing of the system connection to ensure that the entire system forms a closed sterile channel when connected. Then open the active butterfly valve 3 and the passive butterfly valve 5 switches and perform an online leak test on the system to ensure the integrity of the system connection.

[0061] (2) After the leak test is passed, the active butterfly valve 3 and the passive butterfly valve 5 are kept open, and steam is introduced into the system so that pure steam can flow between the reversible drug storage tank 1 and the sterile drug storage bag 11. The entire system is sterilized online with moist heat (121°C, 30 minutes). After the sterilization is completed, the system maintains a slightly positive pressure state against the background environment.

[0062] (3) The active butterfly valve 3 and the passive butterfly valve 5 are closed, and 3 kg of sterile powder prepared by the aseptic production process is transported and stored in the reversible drug storage tank 1.

[0063] (4) Open the active butterfly valve 3 and the passive butterfly valve 5 in sequence, flip the drug storage tank 1 to discharge the material, and transfer the sterile powder to the powder storage tank 7 along the closed sterile channel. After observing the sterile powder transfer through the sight glass, close the passive butterfly valve 5 and the active butterfly valve 3.

[0064] In this embodiment, the weight of the powder received by the powder storage tank 7 is 2.7 kg, and the powder yield is 90%.

[0065] It can be seen from Examples 2 and 3 that after adopting the transfer method of the present invention, the aseptic transfer yield of the drug can reach more than 90%, which is a high yield. The traditional sterile powder discharging method generally adopts a vacuum suction method, which has a large drug residue and a low yield (<70%). Therefore, the discharging transfer method of the present invention can significantly improve the product yield.

[0066] Finally, it should be noted that the above specific embodiments are only used to explain in detail the purpose, technical solutions and beneficial effects of the present invention. It should be understood that the above is only a specific implementation method of the present invention and is not used to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to the above specific embodiments, ordinary technicians in this field should understand that it is still possible to modify the technical solutions described in the above embodiments, or to replace or improve some or all of the technical features therein. These modifications, equivalent replacements, and improvements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present invention, and they should all be covered by the scope of the claims and description of the present invention.

Claims

1. A double butterfly valve sterile drug transfer system, characterized in that: It comprises a reversible medicine storage tank (1), an active butterfly valve (3), a passive butterfly valve (5), a powder storage tank (7) and a sterile medicine liquid storage bag (11); The discharge port (101) of the reversible drug storage tank (1) is connected to the active butterfly valve (3) via a first connecting piece (2), the active butterfly valve (3) is connected to the passive butterfly valve (5) via a second connecting piece (4), and the passive butterfly valve (5) is connected to the feed port of the powder storage tank (7) via a third connecting piece (6); The discharge port of the powder storage tank (7) is provided with a diaphragm valve (8), and the discharge port of the powder storage tank (7) is connected to a sterile liquid medicine storage bag (11), and the discharge port of the powder storage tank (7) is also connected to a steam discharge pipeline (13); When transferring liquid medicine, the powder storage tank (7) is used as a transfer pipeline. When transferring powder, the bottom of the powder storage tank (7) is sealed and the powder storage tank (7) is used as a storage tank to receive powder.

2. A double butterfly valve sterile drug transfer system according to claim 1, characterized in that: The first connecting member (2) is a clamp.

3. A double butterfly valve sterile drug transfer system according to claim 1, characterized in that: The second connecting member (4) comprises a first clamp (401), a connecting head (402) and a second clamp (403), wherein the first clamp (401) clamps the active butterfly valve (3) and the connecting head (402) together, and the second clamp (403) clamps the connecting head (402) and the passive butterfly valve (5) together.

4. A double butterfly valve sterile drug transfer system according to claim 1, characterized in that: The third connecting member (6) is a clamp.

5. The double butterfly valve sterile drug transfer system according to claim 1, characterized in that: The discharge port of the powder storage tank (7) is connected to the sterile liquid medicine storage bag (11) via a sterile liquid medicine transfer pipeline (10).

6. A double butterfly valve sterile drug transfer system according to claim 1, characterized in that: A second diaphragm valve (12) is provided at the inlet end of the steam exhaust pipeline (13).

7. The double butterfly valve sterile drug transfer system according to claim 1, characterized in that: The discharge port of the powder storage tank (7) is connected to the inlet of the three-way joint (9), and the two outlets of the three-way joint (9) are respectively connected to the sterile liquid transfer pipeline (10) and the steam discharge pipeline (13).

8. A method for aseptic drug transfer, characterized in that: The following steps are involved: Open the active butterfly valve (3) and the passive butterfly valve (5), and introduce steam into the system so that the steam can flow between the reversible drug storage tank (1) and the sterile drug storage bag (11). Perform online wet heat sterilization at 120-130°C for 15-30 minutes. After steam sterilization is completed, keep the system in a slightly positive pressure state. The active butterfly valve (3) and the passive butterfly valve (5) are closed, and the sterile medicine is delivered into the reversible medicine storage tank (1); When the transferred drug is a sterile liquid, the active butterfly valve (3), the passive butterfly valve (5) and the diaphragm valve (8) are opened in sequence, and clean compressed air is introduced into the reversible drug storage tank (1) with a pressure of ≤0.20 MPa. The sterile liquid is transferred to the sterile liquid storage bag (11) through the powder storage tank (7) and the sterile liquid transfer pipeline (10) in sequence. After the transfer is completed, the diaphragm valve (8), the passive butterfly valve (5) and the active butterfly valve (3) are closed; When the transferred drug is sterile powder, the diaphragm valve 1 (8) is kept closed, and the active butterfly valve (3) and the passive butterfly valve (5) are opened in sequence to transfer the sterile powder into the powder storage tank (7). After the transfer is completed, the passive butterfly valve (5) and the active butterfly valve (3) are closed.

9. A method for aseptic drug transfer according to claim 8, characterized in that: During steam sterilization, the diaphragm valve 2 (12) is opened to discharge steam from the steam discharge line (13).

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