A microsphere processing device

Abstract

The application discloses a microsphere processing device, which belongs to the technical field of drug-loaded microspheres. The microsphere processing device comprises a cylinder, a piston, and a piston rod fixed on one side of the piston, and one side of the cylinder is provided with an injection port; the inner wall of the cylinder is provided with a movable support structure and a fixed blocking structure; wherein the support structure is arranged on the side of the blocking structure close to the injection port; the piston can be embedded and fixed with the support structure and can drive the support structure to move synchronously and reciprocally along the axial direction of the cylinder on the inner wall of the cylinder. The microsphere processing device comprises a liquid collecting area; after the piston and the support structure are embedded and fixed, the area between the piston and the injection port of the cylinder forms the liquid collecting area. The blocking structure can resist the movement of the support structure, so that the piston can be separated from the embedded and fixed support structure and moves along the inner wall of the blocking structure in a sealed manner. By using the microsphere processing device, the microspheres and the drug solution can be sucked into the liquid collecting area for drug loading, and the drug loading operation is simplified.

Description

Technical Field

[0001] This application relates to the field of drug-loaded microsphere technology, and more specifically, to a microsphere processing device. Background Technology

[0002] Embolization microspheres are tiny particles used for endovascular embolization therapy, widely applied in interventional radiology and vascular surgery. They treat diseases by blocking blood flow in specific blood vessels. In clinical use, the drug-loaded solution for the embolization microspheres needs to be prepared on-site. This requires separately drawing up the microspheres and the drug solution, mixing them, and then allowing the microspheres to adsorb or swell to load the drug. This process involves multiple measuring containers and steps, which is not only cumbersome but also leads to loss of drug solution and microsphere content, affecting subsequent monitoring of the drug loading on the microspheres. Utility Model Content

[0003] This application provides a microsphere processing device that can perform drug loading on microspheres, simplifying the drug loading operation and facilitating subsequent measurement of the drug loading amount of the microspheres.

[0004] This application is implemented as follows: In a first aspect, an example of this application provides a microsphere processing device, including a cylinder, a piston, and a piston rod fixed to one side of the piston. An injection port is also provided on one side of the cylinder. The inner wall of the cylinder is provided with a movable support structure and a fixed blocking structure, wherein the support structure is located on the side of the blocking structure near the injection port. The piston can be fitted and fixed with the support structure and can drive the support structure to reciprocate synchronously along the axial direction of the cylinder's inner wall. The microsphere processing device includes a liquid collection area; after the piston and support structure are fitted and fixed, a liquid collection area is formed in the area between the piston and the injection port of the cylinder. The blocking structure can resist the movement of the support structure, allowing the piston to disengage from the fitted and fixed support structure and move in a sealed manner along the inner wall of the blocking structure.

[0005] In the above process, a movable support structure is provided on the inner wall of the cylinder. The piston rod can be used to push the piston to engage and fix with the support structure, allowing the piston to drive the support structure to reciprocate synchronously along the axial direction of the cylinder's inner wall. Since the piston can drive the support structure to reciprocate synchronously along the axial direction of the cylinder's inner wall, when drug loading of the microspheres is required, the piston rod can be pushed towards the injection port, moving the piston and support structure to the injection port, bringing the injection port close to the microspheres and drug solution. Then, the piston rod can be pulled away from the injection port to draw in the microspheres and drug solution separately through the injection port. Because the piston and support structure, after being engaged and fixed, form a collection zone between the piston and the injection port, the microspheres and drug solution drawn into the cylinder can fully contact each other in the collection zone, achieving drug loading of the microspheres. In addition, a blocking structure is fixedly installed on the inner wall of the cylinder. When the piston drives the support structure to move to the blocking structure, the blocking structure can resist the support structure and prevent it from moving further, so that the piston can disengage from the fitting and fixing of the support structure and move in a sealed manner along the inner wall of the blocking structure, so as to facilitate subsequent operations such as separating the drug solution or discharging the remaining drug solution in the cylinder.

[0006] By using the aforementioned microsphere processing device to load microspheres with drugs, the interlocking and fixing action of the piston and support structure can draw the microspheres and drug solution into the collection area for mixing. This eliminates the need for multiple containers for measurement, simplifying the drug loading operation and improving the problem of drug solution and microsphere content loss caused by multiple measurements. It also improves the detection accuracy when performing subsequent microsphere drug loading detection. Attached Figure Description

[0007] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the accompanying drawings used in the description of the embodiments or the prior art will be briefly introduced below.

[0008] Figure 1 A schematic diagram showing the piston and support structure in a disengaged state in the microsphere processing device provided in the embodiments of this application; Figure 2 A schematic diagram showing the piston and support structure in a fixed, fitted state in the microsphere processing device provided in the embodiments of this application; Figure 3 Figure A is a partial schematic diagram of the fitting part and piston before they are fitted and fixed; Figure B is a partial schematic diagram of the fitting part and piston after they are fitted and fixed. Figure 4 This is a schematic diagram showing the positional relationship between the first plane of the annular support portion and the filter membrane provided in an embodiment of this application. Figure 5 A top view schematic diagram of the connection between the annular support and the filter membrane provided in an embodiment of this application; Figure 6 An enlarged schematic diagram of the first and second scales in the microsphere processing device provided in the embodiments of this application; Figure 7 A schematic diagram of the liquid collection area of ​​the microsphere processing device provided in the embodiments of this application; Figure 8 A schematic diagram of the separation zone and measurement zone of the microsphere processing device provided in an embodiment of this application; Figure 9 A schematic diagram of the drainage area of ​​the microsphere treatment device provided in the embodiments of this application; Figure 10 This is a schematic diagram illustrating the operation of the microsphere processing device for discharging drug-loaded microspheres provided in the embodiments of this application.

[0009] Icons: 100-Microsphere processing device; 1-Cylinder; 101-Collection zone; 102-Separation zone; 103-Measuring zone; 104-Drainage zone; 2-Piston; 21-Groove structure; 3-Piston rod; 4-Injection port; 5-Support structure; 51-Interlocking part; 510-Protruding structure; 511-Interlocking plane; 512-Interlocking curved surface; 52-Annular support part; 521-First plane; 6-Blocking structure; 7-Filter membrane; 8-First graduation; 9-Drainage port; 10-Second graduation; 11-0 graduation line; 12-One-way valve; 13-Sealing plug; θ1-First tilt angle; θ2-First tilt angle; D1-First direction; D2-Second direction. Detailed Implementation

[0010] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions in the embodiments of this application will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.

[0011] Please see Figure 1 This application provides a microsphere processing device 100, including a cylindrical body 1, a piston 2, and a piston rod 3 fixed to one side of the piston 2. An injection port 4 is also provided on one side of the cylindrical body 1. A movable support structure 5 and a fixed blocking structure 6 are provided on the inner wall of the cylindrical body 1, wherein the support structure 5 is located on the side of the blocking structure 6 near the injection port 4. The piston 2 can be fitted and fixed with the support structure 5, and can drive the support structure 5 to reciprocate synchronously along the axial direction of the cylindrical body 1 within the inner wall of the cylindrical body 1. Please refer to... Figure 7The microsphere processing device 100 includes a liquid collection area 101. After the piston 2 and the support structure 5 are fitted and fixed, the cylinder 1 forms the liquid collection area 101 in the region between the piston 2 and the injection port 4. The blocking structure 6 can resist the movement of the support structure 5, so that the piston 2 can disengage from the fitted and fixed support structure 5 and move in a sealed manner along the inner wall of the blocking structure 6.

[0012] This application utilizes the aforementioned device to adsorb and load drugs onto microspheres or to swell and load drugs onto them. The piston rod 3 is pushed towards the injection port 4 (first direction D1) to engage and fix the piston 2 with the support structure 5, bringing the injection port 4 close to the microspheres or drug solution. Then, the piston rod 3 is pulled away from the injection port 4 (second direction D2) to move the piston 2 and support structure 5 synchronously, thereby allowing the microspheres and drug solution to be drawn in from the injection port 4 under the influence of a pressure difference. Since the engagement and fixation of the piston 2 and support structure 5 creates a collection area 101 between the piston 2 and the injection port 4, the microspheres and drug solution within the suction cylinder 1 can fully contact each other in the collection area 101, achieving drug loading of the microspheres. In addition, a blocking structure 6 is fixedly installed on the inner wall of the cylinder 1. When the piston 2 drives the support structure 5 to move to the blocking structure 6, the blocking structure 6 can resist the continued movement of the support structure 5, so that the piston 2 can be disengaged from the support structure 5 and move in a sealed manner along the inner wall of the blocking structure 6, so as to facilitate subsequent operations such as separating the remaining drug solution or discharging the remaining drug solution.

[0013] It is understood that this application does not limit the simultaneous inhalation of microspheres and drug solution. Microspheres can be inhaled first, followed by the drug solution, or vice versa, as long as the drug solution and the microspheres to be tested can be transported to the collection area 101 within the cylinder 1 for mixing. As an example, dry powder microspheres can be pre-introduced into the cylinder 1 under aseptic conditions, followed by the drug solution. See the schematic diagram after inhalation of microspheres and drug solution. Figure 7 .

[0014] To facilitate further drug loading tests on the drug-loaded microspheres, in some embodiments, please refer to... Figure 1 , Figure 2 and Figure 8 The microsphere processing device 100 provided in this application embodiment includes a separation zone 102. Please continue reading. Figure 1 and Figure 2 A filter membrane 7 is fixedly installed at one end of the support structure 5 near the injection port 4. The injection port 4 and the piston 2 are located on opposite sides of the filter membrane 7. After the piston 2 is detached from the support structure 5, a separation zone 102 is formed in the area between the filter membrane 7 and the piston 2 in the cylinder 1.

[0015] A filter membrane 7 is fixedly installed at one end of the support structure 5 near the injection port 4, with the injection port 4 and piston 2 located on opposite sides of the filter membrane 7. Therefore, when the piston 2 and the support structure 5 are fitted and fixed, the microspheres entering the collection area 101 from the injection port 4 can be located on the side of the filter membrane 7 near the injection port 4. After the microspheres in the collection area 101 have fully contacted the drug solution, the piston rod 3 can be pulled in the second direction D2 away from the injection port 4. The blocking structure 6 resists the movement of the support structure 5, allowing the piston 2 to disengage from the fitted and fixed support structure 5 and move in a sealed manner along the inner wall of the blocking structure 6. At this time, the piston 2 and the filter membrane 7 separate and form a certain space, which is the separation area 102. This space gradually increases as the piston 2 moves in the second direction D2. Therefore, it can be understood that the separation area 102 is a space that can dynamically change with the movement of the piston 2, that is, the separation area 102 is formed in the area of ​​the cylinder 1 corresponding to the filter membrane 7 and the piston 2. See the diagram showing the state after separating the annular support 52 and the piston 2. Figure 1 Then, the cylinder 1 is placed vertically with the injection port 4 facing upwards. The remaining drug solution, which has not been adsorbed or swollen by the microspheres, flows into the separation zone 102 under gravity through the filter membrane 7. The microspheres, however, remain above the filter membrane 7 due to its obstruction, thus separating the remaining drug solution from the drug-loaded microspheres. This allows for subsequent calculation of the drug loading capacity of the microspheres using the remaining drug solution. See the schematic diagram of the separation of the remaining drug solution and the drug-loaded microspheres. Figure 8 .

[0016] As an example, based on the law of conservation of mass, the drug loading of the microspheres can be obtained by recording the mass difference between the initial drug solution delivered to the collection zone 101 and the remaining drug solution flowing into the separation zone 102.

[0017] Understandably, in order for the microspheres to fully adsorb or swell in the drug solution and to retain unadsorbed or swollen residual drug solution, the drug solution introduced into cylinder 1 needs to be in excess.

[0018] As an example, the adsorption or swelling time of the microspheres can be appropriately extended to reduce the probability of excessive residual drug solution due to premature separation of the drug solution caused by an excessively short adsorption or swelling time. As for the method of determining the adsorption or swelling time of the microspheres, it can be done by observing the adsorption or swelling of the microspheres. Once the volume of the microspheres no longer changes, an additional 10-60 minutes of adsorption or swelling can be allowed. Then, the support structure 5 and piston 2 should be separated to allow the remaining drug solution to separate from the microspheres.

[0019] Furthermore, the embodiments of this application do not limit the specific type of the support structure 5. In some embodiments, please refer to... Figure 3The support structure 5 includes an annular support portion 52 and a locking portion 51. The annular support portion 52 is attached to the inner wall of the cylinder 1, and a filter membrane 7 is provided on the side of the annular support portion 52 near the injection port 4. The locking portion 51 is fixedly disposed on the inner side of the annular support portion 52 and can be engaged and fixed with the piston 2.

[0020] When it is necessary to engage and fix the support structure 5 with the piston 2, the piston rod 3 can be moved in the first direction D1 towards the injection port 4, so that the piston 2 extends into the annular support portion 52 and engages and fixes with the engaging portion 51 on the inner side of the annular support portion 52. See the diagram showing the state after the annular support portion 52 and the piston 2 are engaged and fixed. Figure 2 .

[0021] Since the annular support 52 is attached to the inner wall of the cylinder 1, and the outer wall of the annular support 52 can be slidably connected to the inner wall of the cylinder 1 in a sealable manner, when the piston 2 is fitted and fixed to the inner side of the annular support 52, the side wall of the piston 2 can be sealed and connected to the inner wall of the annular support 52, thereby forming a liquid collection area 101 in the area of ​​the cylinder 1 corresponding to the piston 2 and the injection port 4, preventing the drug solution from seeping out of the liquid collection area 101.

[0022] Furthermore, in some embodiments, please continue to refer to Figure 3 and Figure 4 The axial cross-section of the annular support 52 is an inverted L-shape. The side of the inverted L-shape near the injection port 4 includes a first plane 521. The first plane 521 has a first inclination angle θ1, which is the angle between the first plane 521 and the radial direction of the cylinder 1. The first inclination angle θ1 satisfies: 0 ≤ θ ≤ 60°.

[0023] By configuring the annular support portion 52 into an inverted L-shaped structure in axial section, the first plane 521 of the annular support portion 52 near the injection port 4 can be connected to the filter membrane 7, so that the drug solution located above the annular support portion 52 can pass through the filter membrane 7.

[0024] Furthermore, the embodiments of this application do not limit the specific degree of the first tilt angle θ1. As an example, the first tilt angle θ1 can be one of 0°, 10°, 20°, 30°, 40°, 50° or 60° or any range between two of them.

[0025] When the angle between the first plane 521 and the radial direction of the cylinder 1 is 0°, the first plane 521 is a horizontal plane, such as... Figure 3 As shown. When the angle between the first plane 521 and the radial direction of the cylinder 1 is greater than 0° and less than or equal to 60°, the first plane 521 is an inclined plane, as shown. Figure 4As shown, the first plane 521 of the annular support 52 is set as an inclined plane with a first tilt angle θ1. Therefore, the drug solution located at the first plane 521 can flow along the inclined surface to the filter membrane 7, so that the remaining drug solution can pass through the filter membrane 7 to the maximum extent. This facilitates the subsequent calculation of the drug loading of the microspheres based on the remaining drug solution, thereby improving the test accuracy.

[0026] It is understood that the filter membrane 7 can prevent microspheres from passing through the filter membrane 7, and the pore size of the filter membrane 7 should be smaller than the outer diameter of microspheres before adsorption or swelling in the art. This application does not limit the specific pore size of the filter membrane 7; in some embodiments, the mesh size of the filter membrane 7 can be 500-1600 mesh. This application does not limit the specific material of the filter membrane 7, as long as it can filter the drug solution and does not react with the drug solution or the microspheres.

[0027] Furthermore, the embodiments of this application do not limit the specific type of the engaging part 51. In some embodiments, please continue to refer to... Figure 3 The engaging portion 51 includes at least one protruding structure 510 that protrudes radially along the cylinder 1. The protruding structure 510 includes an engaging plane 511 and an engaging curved surface 512 that are tangentially connected. The engaging plane 511 is disposed on the side of the engaging curved surface 512 away from the injection port 4. The engaging plane 511 has a second inclination angle θ2, which is the angle between the engaging plane 511 and the axial direction of the cylinder 1. The second inclination angle θ2 satisfies: 15°≤θ2≤45°. The engaging curved surface 512 includes an arc surface.

[0028] A protruding structure 510 is provided on the inner side of the annular support 52, which protrudes radially along the cylinder 1. At the same time, a groove structure 21 that fits into the protruding structure 510 is provided on the side wall of the piston 2. The protruding structure 510 can be used to engage the groove structure 21 at the piston 2, so as to achieve the engagement, fixation or disengagement of the piston 2 and the support structure 5.

[0029] Specifically, when the piston rod 3 pushes the piston 2 closer to and in contact with the support structure 5 along the first direction D1, the side wall of the piston 2 presses against the protrusion structure 510 of the support structure 5, causing the protrusion structure 510 to be pressed into the interior of the annular support portion 52. When the piston rod 3 continues to be pushed along the first direction D1, when the groove structure 21 of the piston moves to the position of the engaging portion 51, the corresponding space left by the groove structure 21 causes the protrusion structure 510 pressed into the interior of the annular support portion 52 to pop out and fit into the groove structure 21. When the piston continues to be pushed along the first direction D1, since the annular support portion 52 is inverted L-shaped, the horizontal structure on the side of the annular support portion 52 near the injection port blocks the piston 2 from moving forward, thereby making the groove structure 21 and the protrusion structure 510 of the piston 2 fit and fix together and drive the support structure 5 to move forward synchronously.

[0030] When piston rod 3 drives piston 2 to move in the second direction D2 away from injection port 4, the piston 2 can drive the annular support structure 5 to move in the second direction D2 because the engaging and fixing force between piston 2 and protruding structure 510 is greater than the sliding friction between annular support 52 and inner wall of cylinder 1. When piston 2 drives annular support structure 5 to move to blocking structure 6, the blocking structure 6 will abut against annular support 52. The abutting force of blocking structure 6 against annular support 52 is greater than the engaging and fixing force between protruding structure 510 and piston 2, so piston 2 can disengage from protruding structure 510.

[0031] Furthermore, to facilitate a smoother engagement of the piston 2 with the protrusion 510 on the engaging portion 51 along the first direction D1, or a more secure connection with the protrusion 510 on the engaging portion 51 along the second direction D2, please refer to [further details needed]. Figure 3 The protruding structure 510 provided in this embodiment includes a tangentially connected engaging plane 511 and engaging curved surface 512. The engaging plane 511 is located on the side of the engaging curved surface 512 away from the injection port 4. The engaging plane 511 has a second inclination angle θ2, which is the angle between the engaging plane 511 and the axial direction of the cylinder 1. The second inclination angle θ2 satisfies: 15°≤θ2≤45°. The engaging plane 511 with the second inclination angle θ2 allows the piston 2 to slide more smoothly into the annular support portion 52 and engage and fix with the protruding structure 510. When the piston 2 moves along the second direction D2 into the support structure 5 and reaches the blocking structure 6, because the engaging curved surface 512 includes an arc surface and is tangent to the engaging plane 511, the piston 2 will not easily disengage from the support structure 5 due to the resistance of the engaging curved surface 512.

[0032] This application designs the protruding structure 510 as asymmetrical and differentiated, that is, it sets two engaging planes 511 and engaging curved surfaces 512 with different slopes. This makes the thrust of the piston 2 along the first direction D1 through the engaging plane 511 and along the second direction D2 through the engaging curved surface 512 different. Because the slope of the engaging plane 511 is gentle, the piston 2 can pass through the engaging plane 511 more smoothly and easily along the first direction D1, thus achieving engagement with the support structure 5. Because the slope of the engaging curved surface 512 is steeper, it is more difficult for the piston to pass through the engaging curved surface 512 along the second direction D2. Therefore, when the piston 2 engages and fixes the support structure 5 and moves synchronously along the second direction D2, the piston 2 will not easily disengage from the support structure 5 because it is blocked by the engaging curved surface 512, thus moving the support structure 5 more effectively. When the piston 2 moves along the second direction D2 and is blocked by the blocking structure 6, the side wall of the piston 2 can slide and disengage along the tangent surfaces of the engaging plane 511 and engaging curved surface 512 because the engaging plane 511 and engaging curved surface 512 are tangent.

[0033] This application does not limit the specific number and shape of the engaging portion 51. In some embodiments, the engaging portion 51 is a single annular, continuous protrusion 510, or it can be a plurality of discontinuous, non-continuous protrusions 510. At least two protrusions 510 may be arranged radially spaced within the annular support portion 52. Alternatively, the protrusions may be arranged in a circle around the circumference of the annular support portion 52. Alternatively, at least two protrusions 510 may be arranged axially spaced within the annular support portion 52.

[0034] To further facilitate the engagement and fixation of the piston 2 with the protrusion structure 510, in some embodiments, the sidewall of the piston 2 is provided with a groove structure 21 that can engage with the protrusion structure 510.

[0035] Furthermore, in some embodiments, please continue to combine Figure 4 and Figure 5 When the groove structure 21 is engaged with the engagement part 51, the filter membrane 7 is attached to the side of the piston 2 near the injection port 4, so that the drug solution is basically located on the side of the filter membrane 7 near the injection port 4, and can have more sufficient contact with the microspheres located on the side of the filter membrane 7 near the injection port 4, so as to facilitate drug loading of the microspheres.

[0036] Furthermore, the embodiments of this application do not limit the specific material of the annular support portion 52. In some embodiments, the material of the annular support portion 52 includes at least one of silicone or rubber.

[0037] The annular support 52 is made of silicone or rubber, which allows the annular support 52 to slide along the cylinder 1 while also providing a better seal with the inner wall of the cylinder 1, thereby reducing the risk of leakage.

[0038] As an example, the annular support 52 can be disposed inside the cylinder 1 with a slight interference fit. The annular support 52 can undergo slight deformation under the slight pressure of the cylinder 1, thus fitting more tightly against the inner wall of the cylinder 1. At the same time, the appropriate interference fit can also allow it to slide along the inner wall of the cylinder 1 when subjected to the thrust or pull of the piston 2.

[0039] Furthermore, this application does not limit the specific shape of the annular support portion 52, and can make corresponding adjustments according to the shape of the cylindrical body 1. As an example, when the cylindrical body 1 is cylindrical or has an outer square and inner circle shape, the outer wall of the annular support portion 52 can be set to be circular. The inner wall of the annular support portion 52 is not limited; for example, the inner wall of the annular support portion 52 can also be circular or prismatic.

[0040] It is understandable that piston 2 should be a solid structure. Similarly, the shape of piston 2 can be adjusted according to the shape of the inner wall of the annular support 52, so that piston 2 can extend into the annular support 52 and seal against the inner wall of the annular support 52. As an example, when the inner wall of the annular support 52 is circular, piston 2 can be configured as a cylindrical structure.

[0041] In some embodiments, please continue reading Figure 1 The cylinder 1 can be configured as a cylindrical structure. To facilitate the separation of the support structure 5 from the piston 2, the blocking structure 6 can be configured as an annular sleeve structure fixedly connected to the inner wall of the cylinder 1. The inner wall surface of the annular sleeve structure is flush with the inner wall surface of the annular support part 52, and the piston 2 can selectively slide along the inner wall surface of the sleeve. With the sleeve-shaped blocking structure 6 fixedly installed inside the cylinder 1, and the inner wall surface of the blocking structure 6 flush with the inner wall surface of the annular support part 52, the piston 2 can slide along the inner wall surface of the blocking structure 6 until it engages and is fixed with the protruding structure 510 on the inner wall surface of the annular support part 52.

[0042] When piston 2 drives the annular support 52 to move in the second direction D2, when the annular support 52 moves to the end face of the blocking structure 6, the end wall of the blocking structure 6 will abut against the end wall of the annular support 52, restricting the annular support 52 from continuing to move in the second direction D2. At this time, piston 2 can slide from the inner wall surface of the annular support 52 to the inner wall surface of the blocking structure 6, realizing the separation of piston 2 from the annular support 52. The outer wall surface of the blocking structure 6 is fixedly connected to the inner wall surface of the cylinder 1.

[0043] When piston 2 slides to the inner wall of blocking structure 6, piston 2 can be slidably and sealingly connected with the inner wall of blocking structure 6, thereby enabling piston 2 to be slidably and sealingly connected with cylinder 1.

[0044] When the piston 2 slides along the first direction D1 into the annular support portion 52, the piston 2 is sealed to the inner wall of the annular support portion 52, and the outer wall of the annular support portion 52 is slidably sealed to the inner wall of the cylinder 1, thereby enabling a sealable sliding connection between the piston 2 and the cylinder 1.

[0045] This application does not limit the specific shape of the blocking structure 6, as long as the outer wall of the blocking structure 6 can be sealed and fixedly connected with the inner wall of the cylinder 1, and the inner wall of the blocking structure 6 can be flush with the inner wall of the annular support 52.

[0046] Furthermore, this application does not limit the specific material of the cylinder 1. In some embodiments, the cylinder 1 can be a transparent structure made of a transparent material. As an example, the cylinder 1 can be made of glass or acrylic. Using a transparent material to prepare the cylinder 1 allows for more direct observation of the microsphere adsorption or swelling and the separation of the drug solution within the cylinder 1.

[0047] Furthermore, to facilitate viewing the volume of the initial drug solution within the input cylinder 1, in some embodiments, please refer to [the documentation / reference needed]. Figure 1 When the support structure 5 comes into contact with the blocking structure 6, the cylinder 1 has a second scale 10 on the side of the support structure 5 near the injection port 4, so that the volume of microspheres and drug solution in the collection area 101 can be measured.

[0048] Furthermore, the cylinder 1 is provided with a first scale 8 corresponding to the area where the blocking structure 6 is located. The first scale 8 includes a 0 scale line 11 on the side away from the injection port 4. When the edge of the piston 2 near the injection port 4 coincides with the 0 scale line 11, the cylinder 1 forms a measurement area 103 in the space between the piston 2 and the filter membrane 7. When the piston 2 moves along the second direction D2 to the 0 scale line 11, the volume of the remaining drug solution on the piston 2 can be read and measured through the first scale 8.

[0049] It should be noted that the separation zone 102 and the measuring zone 103 have a partially overlapping space. The separation zone 102 gradually increases in size as the piston 2 moves in the second direction D2, thereby achieving the separation of the microspheres and the remaining drug solution; for example... Figure 8 As shown, when piston 2 moves to the 0 mark 11, the separation zone 102 is the measurement zone 103. That is to say, in the measurement zone 103, the separation of microspheres and drug solution remaining after drug loading is realized, and the volume of the remaining drug solution is measured at the same time.

[0050] In some embodiments, the barrier structure 6 may be made of a transparent material. As an example, the material of the barrier structure 6 includes at least one of polystyrene or polycarbonate.

[0051] In some embodiments, please continue reading Figure 6This allows the accuracy of the first graduation 8 to be higher than that of the second graduation 10. It is understood that the effective inner diameter of the cylinder 1 is reduced due to the obstruction structure 6 in the measuring area 103. Therefore, the effective inner diameter of the cylinder 1 in the measuring area 103 is smaller than its effective inner diameter in the collection area 101. This results in the first graduation 8 in the measuring area 103 having higher accuracy than the second graduation 10 in the collection area 101. For example, the accuracy of the first graduation 8 is 0.1 ml, and the accuracy of the second graduation 10 is 0.2 ml, allowing for a more precise measurement of the remaining drug solution volume in the measuring area 103.

[0052] Furthermore, after measuring the volume of the remaining drug solution, in order to facilitate the discharge of the remaining drug solution, in some embodiments, please combine... Figure 1 and Figure 9 The cylinder body 1 includes a drainage area 104. A drainage port 9 is provided on the side wall of the cylinder body 1 corresponding to the blocking structure 6. The drainage port 9 is located on the side of the 0 mark 11 away from the injection port 4. The area of ​​the cylinder body 1 corresponding to the drainage port 9 is the drainage area 104. Please continue reading. Figure 2 When the support structure 5 abuts against the blocking structure 6, the distance between the drain port 9 and the edge of the support structure 5 near the injection port 4 is L1, and the distance between the injection port 4 and the edge of the support structure 5 near the injection port 4 is L2, where L1 > L2.

[0053] The drain port 9 is positioned on the side of the first scale 8 away from the injection port 4, at the 0 mark 11. When the piston 2 slides to the position of the 0 mark 11, the volume of the remaining drug solution can be determined according to the first scale 8. Then, the piston 2 is moved to the drain port 9 below the first scale 8 to drain the remaining drug solution.

[0054] To more clearly observe whether piston 2 has moved to the 0 mark 11, please continue reading. Figure 1 The 0 mark 11 can be extended appropriately to make it more prominent.

[0055] The remaining drug solution discharged from the drain port 9 is collected by a container to facilitate subsequent component or concentration testing of the remaining drug solution.

[0056] For further information, please refer to [link / reference]. Figure 1 Furthermore, a one-way valve 12 can be installed at the drain port 9 to allow the remaining drug solution to be discharged outside the cylinder 1, thus preventing drug solution outside the cylinder 1 from entering the cylinder 1.

[0057] To improve the efficiency of removing residual drug solution, in some embodiments, please refer to... Figure 9A sealing plug 13 can be detachably connected to the injection port 4. By sealing the injection port 4 with the sealing plug 13 and pushing the piston 2 forward, the remaining drug solution can be discharged from the drain port 9 through the air pressure difference. As an example, such as Figure 9 As shown, the sealing plug has a cap-like structure. Alternatively, as an example, the sealing plug 13 can be a rubber plug, which may include a plug plunger and a plug head connected to each other. The plug head is larger than the plug plunger, allowing the plug plunger to extend into the injection port 4, and the plug head to abut against the end of the injection port 4 to prevent the plug plunger from entering the cylinder 1.

[0058] In one optional embodiment, the microsphere processing device 100 of this application includes a collection zone 101, a separation zone 102, a measurement zone 103, and a discharge zone 104. The collection zone 101 can perform adsorption-loaded or swelling-loaded drug processing on the microspheres; the separation zone 102 can perform filtration-separation processing on the microspheres; the measurement zone 103 can perform volume measurement processing on the remaining drug solution; and the discharge zone 104 can discharge the remaining drug solution. This device integrates multiple microsphere processing functions, realizing convenient sampling of microspheres and drug solutions, drug loading processing, drug-loaded microsphere filtration, filtrate volume measurement, and discharge. It covers the entire process of drug-loaded microsphere discharge, is simple and fast, avoids multiple sample exposures, reduces the risk of sample contamination, and improves the accuracy of subsequent sample detection.

[0059] Furthermore, this application does not specify the morphology of the microspheres loaded with the drug solution. The microspheres can be wet bulbs, i.e., microspheres in a swollen state, or dry bulbs, i.e., microsphere powder in a dry state. When the microsphere processing device 100 of this application is used to process drug-loaded wet bulbs, the wet bulbs can generally fix specific drugs onto the microspheres through ion adsorption. However, some drugs cannot be bound to the microspheres through ion adsorption. Therefore, the morphology of dry bulbs can be selected for drug loading by swelling the drug solution. That is, after the microspheres swell, they can physically accommodate a portion of the drug, thus achieving the effect of drug loading. At this time, during the swelling process of the dry bulbs, not only a certain amount of drug is adsorbed, but also a certain volume of solution is adsorbed. Therefore, the detection of the remaining volume of the drug solution is essential. The microsphere processing device 100 of this application can effectively handle the detection of the remaining volume of the drug solution after the dry bulbs are swollen and loaded with drug, greatly facilitating the subsequent detection of the drug loading of the microspheres and effectively improving the detection accuracy of the drug loading of the microspheres.

[0060] In a second aspect, embodiments of this application also provide a microsphere processing method. Using the microsphere processing apparatus 100 provided in the first aspect, drug loading treatment is performed on the microspheres, including the following steps: Step S1: Push the piston rod 3, causing the piston 2 to move along the first direction D1 until the piston 2 and the support structure 5 are engaged and fixed. The first direction D1 is along the axial direction of the cylinder 1 and close to the injection port 4.

[0061] Step S2: Pull the piston rod 3, causing the piston 2 and support structure 5 to move synchronously along the second direction D2, drawing in the microspheres and drug solution through the injection port 4 respectively. Continue pulling the piston rod 3 until the piston 2 moves the support structure 5 to the blocking structure 6 and then stops. After standing for a period of time, the microspheres and drug solution will be in full contact in the collection area 101; wherein, the second direction D2 is opposite to the first direction D1. See the schematic diagram after the microspheres and drug solution are drawn into the collection area 101. Figure 7 .

[0062] After the piston 2 and the support structure 5 are fitted and fixed, a liquid collection area 101 is formed in the area between the piston 2 and the injection port 4 on the cylinder 1. The injection port 4 is brought close to the microspheres and the drug solution in turn. Then, the piston rod 3 is used to pull the piston 2 and the support structure 5 in a second direction D2 away from the injection port 4. Under the action of the air pressure difference, the microspheres and the drug solution can be drawn into the liquid collection area 101 in turn from the injection port 4, so that the microspheres and the drug solution can be fully mixed in the liquid collection area 101, and the microspheres are drug-loaded.

[0063] As an example, the initial volume of the drug solution input into the collection zone 101 can be slightly excessive. The adsorption or swelling time of the microspheres can also be appropriately extended to reduce the probability of excessive residual drug solution due to premature separation of the drug solution caused by too short an adsorption or swelling time.

[0064] Furthermore, when a filter membrane 7 is fixedly disposed at one end of the support structure 5 near the injection port 4, and the injection port 4 and the piston 2 are located on opposite sides of the filter membrane 7, the processing method further includes separating the drug-loaded microspheres and the remaining drug solution. That is, after step S2, the following steps are included: Step S3: Continue to pull the piston rod 3 along the second direction D2, causing the piston 2 to disengage from the support structure 5. The drug solution in the collection area 101 is filtered through the filter membrane 7 into the separation area 102 between the filter membrane 7 and the piston 2, and the drug-loaded microspheres are retained on the filter membrane 7.

[0065] As an example, after the piston 2 is detached from the support structure 5, the cylinder 1 can be placed vertically with the injection port 4 facing upwards. This allows the remaining drug solution to be filtered through the filter membrane 7 to the separation zone 102 under gravity, while the drug-loaded microspheres remain on the filter membrane 7. This separation of the remaining drug solution from the drug-loaded microspheres facilitates subsequent calculation of the drug loading capacity of the microspheres based on the remaining drug solution. See the schematic diagram of the separation of the drug-loaded microspheres and the remaining drug solution. Figure 8 As shown.

[0066] Furthermore, when the cylinder 1 of the microsphere processing device 100 is transparent, and a first scale 8 is provided in the area of ​​the cylinder 1 corresponding to the location of the blocking structure 6, the first scale 8 including a 0 scale line 11 on the side away from the injection port 4, the processing method further includes volume measurement of the remaining drug solution and measurement of the drug loading of the drug-loaded microspheres. That is, after step S3, the following steps are included: Step S4: Continue pulling piston rod 3 along the second direction D2 until the edge of piston 2 near injection port 4 coincides with the 0 mark 11 (see...). Figure 8 (As shown). The volume of the remaining drug solution is measured as V1 using the first scale 8, and the drug loading capacity of the drug-loaded microspheres is calculated using the formula m = V0C0 - V1C1, where C0 is the initial drug concentration, V0 is the initial drug solution volume, and C1 is the remaining drug concentration.

[0067] Furthermore, when the side wall of the cylinder 1 is provided with a drain port 9 corresponding to the blocking structure 6, and the drain port 9 is located on the side of the 0 mark 11 away from the injection port 4, the processing method further includes draining the remaining drug solution. That is, after step S4, the following is included: Step S5: Continue pulling the piston rod 3 along the second direction D2, so that the piston 2 approaches and passes the drain port 9, reaching the side of the drain port 9 away from the injection port 4. Tilt the cylinder 1 to discharge the remaining drug solution from the drain port 9. See [link to relevant documentation]. Figure 9 As shown.

[0068] As an example, after measuring the volume V1 of the remaining drug solution through the first scale 8, the remaining drug solution can be drained, and the drug concentration in the remaining drug solution can be detected using a concentration detection device.

[0069] Furthermore, the processing method provided in this application embodiment also includes a process for removing the drug-loaded microspheres remaining on the filter membrane 7. That is, after step S5, the following steps are included: Step S6: Push piston rod 3 along the first direction D1 until piston 2 and support structure 5 are engaged and fixed. Continue pushing piston rod 3 along the first direction D1. Piston 2 drives support structure 5 and filter membrane 7 to move synchronously, and discharges drug-loaded microspheres on filter membrane 7 from injection port 4. See [link to relevant documentation]. Figure 10 As shown.

[0070] By pushing the piston 2 in the first direction D1 closer to the injection port 4 by the piston rod 3, the support structure 5 and the filter membrane 7 can move synchronously, and the drug-loaded microspheres on the filter membrane 7 can be discharged from the injection port 4. The discharged drug-loaded microspheres can be collected in a sterile environment and then used.

[0071] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A microsphere processing device, characterized by, It includes a cylinder, a piston, and a piston rod fixed to one side of the piston; the cylinder also has an injection port on one side. The inner wall of the cylinder is provided with a movable support structure and a fixed blocking structure, wherein the support structure is located on the side of the blocking structure near the injection port. The piston can be fitted and fixed with the support structure, and can drive the support structure to reciprocate synchronously along the axial direction of the cylinder on the inner wall of the cylinder. The microsphere processing device includes a liquid collection area. After the piston and the support structure are fitted and fixed, the cylinder forms the liquid collection area in the region between the piston and the injection port. The blocking structure can prevent the support structure from moving, allowing the piston to disengage from the support structure and move in a sealed manner along the inner wall of the blocking structure.

2. The microsphere processing device according to claim 1, characterized in that, The microsphere processing device includes a separation zone. A filter membrane is fixedly provided at one end of the support structure near the injection port, and the injection port and the piston are respectively located on opposite sides of the filter membrane; After the piston detaches from the support structure, the cylinder forms the separation zone in the area between the filter membrane and the piston.

3. The apparatus according to claim 2, characterized in that, The support structure includes a ring-shaped support portion and a locking portion; wherein... The annular support portion is attached to the inner wall of the cylinder, and the filter membrane is provided on the side of the annular support portion near the injection port; The engaging part is fixedly disposed on the inner side of the annular support part and can be engaged and fixed with the piston.

4. The apparatus according to claim 3, characterized in that, The axial cross-section of the annular support is an inverted L-shape. The side of the inverted L-shape near the injection port includes a first plane with a first inclination angle θ1, which is the angle between the first plane and the radial direction of the cylinder. The first tilt angle θ1 satisfies: 0≤θ1≤60°.

5. The apparatus according to claim 3, characterized in that, The engaging portion includes at least one protruding structure that protrudes radially along the cylinder, and the side wall of the piston is provided with a groove structure that engages with the protruding structure. The protruding structure includes a tangentially connected engaging plane and an engaging curved surface, wherein the engaging plane is located on the side of the engaging curved surface away from the injection port; wherein, The engaging plane has a second tilt angle θ2, which is the angle between the engaging plane and the axial direction of the cylinder. The second tilt angle θ2 satisfies: 15°≤θ2≤45°. The engagement surface includes a circular arc surface.

6. The apparatus according to claim 3, characterized in that, The blocking structure is fixed to the inner wall of the cylinder, and the inner wall surface of the blocking structure is flush with the inner wall surface of the support part. The piston has a groove structure on its side wall that engages with the engaging part. When the groove structure engages with the engaging part, the filter membrane is attached to the side of the piston near the injection port.

7. The apparatus according to claim 2, characterized in that, The cylindrical body includes a measuring area. The cylindrical body is a transparent structure. The cylindrical body is provided with a first scale corresponding to the area where the blocking structure is located. The first scale includes a 0 scale line on the side away from the injection port. When the edge of the piston near the injection port coincides with the 0 mark, the cylinder forms the measurement area in the space between the piston and the filter membrane.

8. The apparatus according to claim 7, characterized in that, The cylinder includes a drainage area, and a drainage port is provided on the side wall of the cylinder corresponding to the blocking structure. The drainage port is located on the side of the 0 mark away from the injection port, and the area of ​​the cylinder corresponding to the drainage port is the drainage area. When the supporting structure abuts against the blocking structure, the distance between the drain port and the edge of the supporting structure near the injection port is L1, and the distance between the injection port and the edge of the supporting structure near the injection port is L2, wherein L1 > L2.

9. The apparatus according to claim 7, characterized in that, When the supporting structure abuts against the blocking structure, the cylinder body has a second graduation on the side of the supporting structure near the injection port, wherein, The accuracy of the first scale is higher than that of the second scale.

10. The apparatus according to claim 2, characterized in that, The mesh size of the filter membrane is 500-1600 mesh.

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