Preparation device and production process of microspherical ceftiofur hydrochloride nanoemulsion injection

Abstract

The invention discloses a microsphere-shaped ceftiofur hydrochloride nanoemulsion injection preparation device and a production process, and relates to the technical field of injection preparation equipment, and the microsphere-shaped ceftiofur hydrochloride nanoemulsion injection preparation device comprises a sterile tank body and a supporting piece; a first mounting frame and a second mounting frame are arranged on one side of the supporting piece, the first mounting frame is rotationally connected to the supporting piece, the second mounting frame is rotationally connected to the first mounting frame, the rotating axis of the first mounting frame is perpendicular to the rotating axis of the second mounting frame, and the sterile tank body is fixedly connected with the second mounting frame; the axis of the sterile tank body is eccentrically arranged relative to the rotating axis of the second mounting frame, and the sterile tank body rotates around the rotating axis of the first mounting frame while rotating along with the second mounting frame, so that the sterile tank body does three-dimensional compound motion in the space; a stirring disc is movably arranged in the sterile tank body, and the stirring disc can reciprocate in the sterile tank body along the axis direction of the sterile tank body by virtue of the gravity of the stirring disc. The device has the effects of enhancing the material mixing effect and the sampling randomness.

Description

TECHNICAL FIELD

[0001] The application relates to the technical field of injection preparation equipment, in particular to a microspherical cefetamet pivoxil hydrochloride nanoemulsion injection preparation device and a production process. BACKGROUND

[0002] The microspherical cefetamet pivoxil hydrochloride nanoemulsion injection is a high-tech, long-acting veterinary antibiotic specially designed for pigs, cattle and other domestic animals. First, cefetamet pivoxil hydrochloride is the effective component of the medicine, which is a third-generation cephalosporin antibiotic specially used for veterinary, has a wide antibacterial range and is very effective in treating respiratory tract and urinary system bacterial infections (such as pig's pneumonia, pleuropneumonia, cattle's shipping fever, etc.) of pigs and cattle. Second, the nanoemulsion is a preparation technology, which makes the water-insoluble medicine into nano-level small particles uniformly dispersed in liquid, so as to increase the stability of the medicine, promote the absorption of the body, reduce the irritation and pain of the injection site. Third, the microsphere is to wrap the medicine in a microsphere made of biodegradable material (like absorbable surgical suture), and after being injected into the animal body, the "microsphere medicine warehouse" will slowly degrade in the muscle and continuously and stably release the medicine for 7 days or even longer.

[0003] The preparation steps generally include preparation of cefetamet pivoxil hydrochloride microspheres, preparation of nanoemulsion matrix (carrier), sterile mixing and finally filling and other process steps. The preparation of cefetamet pivoxil hydrochloride microspheres is to wrap cefetamet pivoxil hydrochloride in biodegradable polymer microspheres to form a "medicine warehouse", including steps of preparing oil phase and water phase, emulsifying, extracting and collecting drying. The preparation of nanoemulsion matrix (carrier) is mainly to prepare a stable, safe and absorption-promoting nanoemulsion serving as a microsphere suspension carrier. The prepared nanoemulsion is rapidly cooled to room temperature. Since the nanoemulsion droplets are small enough, the nanoemulsion can be filtered and sterilized through a 0.22-micron filter membrane to obtain a sterile nanoemulsion matrix. Finally, the sterile mixing step needs to use a sterile stirring device to perform gentle and low-speed stirring, so that the microspheres are uniformly suspended in the nanoemulsion matrix to form the final microspherical cefetamet pivoxil hydrochloride nanoemulsion injection.

[0004] The sterile mixing step is very critical, and the stirring in this step cannot be too violent, so as not to damage the structure of the microspheres or cause the nanoemulsion to break. The mixing purpose is "mixing", not "crushing". The conventional mixing device such as a stirring tank generally uses internal stirring blades to stir and mix the material, but the stirring effect of the stirring blades on the suspended material is not ideal, and if the speed is not properly controlled, the hard stirring blades can easily crush the microspheres in the rotating process, affecting the quality of the final product. SUMMARY

[0005] In order to improve the unsatisfactory stirring effect of the conventional stirring device, and the microspheres are easily stirred to pieces by the stirring blades, thereby affecting the quality of the final product. The application provides a microspherical cefetamet pivoxil hydrochloride nanoemulsion injection preparation device and production process.

[0006] In one aspect, the application provides a microspherical cefetamet pivoxil hydrochloride nanoemulsion injection preparation device, which adopts the following technical scheme: A microspherical cefetamet pivoxil hydrochloride nanoemulsion injection preparation device, comprising A sterile tank body for containing the mixture to be mixed, the sterile tank body is provided with a feeding port at one end and a discharging port at the other end; A support for placing on the ground and supporting the sterile tank body, the support is provided with a first mounting bracket and a second mounting bracket on one side, the first mounting bracket is rotatably connected to the support, the second mounting bracket is rotatably connected to the first mounting bracket, the rotation axes of the first mounting bracket and the second mounting bracket are perpendicular to each other, the sterile tank body is fixedly connected to the second mounting bracket, and the axis of the sterile tank body is eccentrically arranged relative to the rotation axis of the second mounting bracket, when the sterile tank body rotates with the second mounting bracket, the sterile tank body also rotates around the rotation axis of the first mounting bracket, so that the sterile tank body makes three-dimensional compound motion in space; A stirring disc movably arranged in the sterile tank body, the stirring disc can reciprocate along the axis of the sterile tank body in the sterile tank body by its own gravity, so as to actively mix and stir the material in the sterile tank body.

[0007] Optionally, the first mounting bracket is a U-shaped bracket, the U-shaped opening of the first mounting bracket faces away from the support, the rotation axis of the first mounting bracket is horizontal and coincides with the symmetry axis of the U-shaped bracket, the U-shaped middle segment protruding part of the first mounting bracket is rotatably connected to the support, and the second mounting bracket and the sterile tank body are arranged at the opening position of the first mounting bracket.

[0008] Optionally, the second mounting bracket is an L-shaped bracket, one end of the second mounting bracket is rotatably connected to the inner side wall of one end of the first mounting bracket, the other end of the second mounting bracket is fixedly connected to one end of the sterile tank body, the end of the sterile tank body away from the second mounting bracket is hingedly connected to the other end of the first mounting bracket, the sterile tank body and the second mounting bracket synchronously rotate relative to the first mounting bracket as a whole, and the axis of the sterile tank body is eccentrically arranged relative to the common rotation axis of the sterile tank body and the second mounting bracket.

[0009] Optionally, a guide column is arranged inside the sterile tank body, the guide column is arranged along the axis of the sterile tank body, a spiral guide groove is formed in the outer wall of the guide column along the axis of the guide column, and the inner wall of the stirring disc is slidably connected to the spiral guide groove, so that the stirring disc can synchronously rotate when moving along the axis of the guide column.

[0010] Optionally, the stirring disc comprises a stirring base and a plurality of stirring rings, the stirring base is coaxially arranged with the guide column and is slidingly connected to the guide column, a plurality of through holes are formed in the stirring base, the plurality of stirring rings are gradually increased in diameter and concentrically arranged at the outer circle of the stirring base, the plurality of stirring rings are fixedly connected to each other, and the stirring ring at the innermost circle is fixedly connected to the stirring base.

[0011] Optionally, a retractable sampling tube is arranged on the stirring base and extends out of the stirring base and the sterile tank body, one end of the sampling tube is arranged to extend out of the stirring base and divergently extend, the other end of the sampling tube is arranged to extend out of the sterile tank body and be close to one end of the second mounting rack, the sampling tube is retractably moved along the stirring base in the axial direction of the sterile tank body, and a suction assembly is arranged on the outer wall of the sterile tank body at the end where the sampling tube extends out, the suction assembly can extract the material in the sterile tank body through the sampling tube to realize sampling.

[0012] Optionally, the suction assembly comprises a sealed closed chamber, the closed chamber is arranged on the end of the sterile tank body in a sealing manner, a suction member and a sample collection chamber are arranged in the closed chamber, the outlet of the sample collection chamber is communicated with the suction member, the inlet of the sample collection chamber is communicated with the sampling tube, a check valve is arranged between the sample collection chamber and the sampling tube to allow the material to enter the sample collection chamber through the sampling tube, a detection branch pipe is communicated with the side wall of the sample collection chamber close to the sampling tube, one end of the detection branch pipe away from the sample collection chamber extends out of the closed chamber and is in a self-sealing state.

[0013] Optionally, a hydrophobic air-permeable member is arranged between the suction member and the sample collection chamber, the hydrophobic air-permeable member allows airflow to pass through and blocks liquid, a three-way valve is further arranged between the check valve and the sampling tube, two interfaces of the three-way valve are respectively communicated with the check valve and the sampling tube, and the last interface is used for external connection of a cleaning device, a backflushing interface is arranged on the pipeline between the hydrophobic air-permeable member and the suction member, and the backflushing interface is in a self-sealing state.

[0014] In another aspect, the application also provides a production process of the microspherical ceftiofur hydrochloride nanoemulsion injection, and the injection is prepared by using the microspherical ceftiofur hydrochloride nanoemulsion injection preparation device. S1: uniformly dispersing water-soluble ceftiofur hydrochloride in an oil phase to form a stable nanoemulsion, using biodegradable polylactic acid-glycolic acid copolymer high molecular material to wrap the nanoemulsion prepared in the previous step to form a microemulsion, collecting the formed microspheres by centrifugation or filtration, repeatedly washing the microspheres with purified water to remove residual organic solvents and surfactants, and finally freeze-drying to obtain dry microsphere powder; S2: quantitative microspheres powder and dispersion medium fluid are injected through the feed port of the sterile tank, then the feed port is closed, the first mounting frame and the second mounting frame are respectively started, the sterile tank rotates with the second mounting frame relative to the first mounting frame, and the sterile tank performs inclined eccentric rotation relative to the rotation axis of the second mounting frame, while the first mounting frame rotates around its own axis to drive the second mounting frame and the sterile tank to rotate together, the superimposed rotation of the first mounting frame and the second mounting frame around their own axes makes the sterile tank perform slow and irregular three-dimensional compound motion in space, and the materials in the sterile tank move irregularly and are fully and gently mixed under the action of gravity; S3: after mixing, the materials in the sterile tank are sampled and detected, and after passing the detection, the materials are aseptically filled.

[0015] In summary, the present application has at least one of the following beneficial effects: 1. By adopting two groups of mounting frames to drive the sterile tank to move, the irregularity of the rotation of the sterile tank in three-dimensional space is enhanced, specifically, the first mounting frame and the second mounting frame are provided, the first mounting frame is a U-shaped support, and the rotation axis of the first mounting frame is horizontal, the second mounting frame and the sterile tank are located at the opening of the U-shaped support, when the first mounting frame rotates, the second mounting frame and the sterile tank can be driven to rotate around the horizontal axis, in the process of the up-down rotation of the sterile tank, the materials in the sterile tank will flow back and forth in the vertical direction under the action of gravity to realize the mixing of the materials, when the second mounting frame drives the sterile tank to rotate, since the rotation axis of the second mounting frame is vertical, the sterile tank will also rotate around the vertical rotation axis, and there is an inclined angle between the axis of the sterile tank and the rotation axis of the second mounting frame, so that the sterile tank will perform horizontal and conical shaking around the vertical rotation axis, combined with the rotation of the first mounting frame around the horizontal axis, and different non-integer multiple relationship rotation speeds can be set for the first mounting frame and the second mounting frame, the sterile tank will first rotate with the first mounting frame, in each moment of the rotation, the eccentric rotation of the sterile tank around the vertical rotation axis will exert a transverse and circular pushing force on the sterile tank, which means that the direction and posture of the transverse pushing force on the sterile tank are always different when the sterile tank is at the same position in space, and it is this never-repeating motion track that makes the materials in the sterile tank be stirred from all directions and at all angles, and any area that may be settled due to gravity or centrifugal force will be broken and washed away by the new motion posture in the next moment, so that the materials are fully mixed; 2. By setting a stirring disc inside the aseptic tank body, and setting a guide column along the axis inside the aseptic tank body, the outer wall of the guide column is provided with a spiral guide groove, the stirring disc is slidingly connected to the spiral guide groove, when the aseptic tank body is flipped up and down along with the first mounting frame, the stirring disc moves along the guide column by gravity, and the stirring disc rotates around the guide column while sliding, and the stirring disc includes a stirring base and a plurality of concentric stirring rings, when the stirring disc slides along the guide column, the plurality of concentric stirring rings can stir the material up and down, the stirring disc rotates while moving up and down, and the material can be spirally stirred while being flipped up and down, the process does not require any driving source, the stirring of the stirring disc on the material completely relies on the flipping action of the aseptic tank body in space, and the material in the aseptic tank body can be further fully mixed; 3. By penetrating a retractable sampling tube on the stirring base of the stirring disc, one end of the sampling tube can reciprocate along the axis of the guide column, the sampling tube correspondingly performs the retracting movement in the process, the other end of the sampling tube penetrates out of the aseptic tank body and communicates with the sample collection bin, the outlet of the sample collection bin is connected with a suction member, after the aseptic tank body is mixed for a predetermined time, the suction member evacuates the sample collection bin to generate negative pressure in the sample collection bin, the mixed material in the aseptic tank body enters the sample collection bin along the sampling tube under the action of atmospheric pressure to complete the collection of the sample, the sample collected in the sample collection bin can be used for material uniformity detection after mixing, since the stirring disc reciprocates in the aseptic tank body after the material is mixed, the sampling end of the sampling tube also reciprocates in the aseptic tank body, so that the sampling tube can sample the material in the aseptic tank body at random positions, and the randomness of sampling is greatly improved. BRIEF DESCRIPTION OF DRAWINGS

[0016] Figure 1 It is a structural schematic diagram of the whole appearance of the preparation device according to Embodiment 1 of the present application; Figure 2 It is a partial schematic diagram of the movement structure of the aseptic tank body according to Embodiment 1 of the present application; Figure 3 It is a sectional view schematic diagram of the internal structure of the aseptic tank body according to Embodiment 1 of the present application; Figure 4 It is a partial schematic diagram of the stirring disc structure according to Embodiment 1 of the present application; Figure 5 It is a sectional view schematic diagram of the internal structure of the closed bin according to Embodiment 1 of the present application; Figure 6 It is a partial schematic diagram of the internal structure of the closed bin according to Embodiment 1 of the present application.

[0017] Explanation of reference numerals in the attached drawings: 1. Aseptic tank; 11. Inlet; 12. Outlet; 13. Guide column; 131. Spiral guide groove; 14. Mounting base; 2. Support component; 21. First mounting bracket; 211. Drive motor; 22. Second mounting bracket; 221. Transmission gear; 3. Stirring disc; 31. Stirring base; 32. Stirring ring; 33. Limiting seat; 4. Sampling tube; 5. Sealed chamber; 51. Suction component; 52. Sample collection chamber; 521. Detection branch pipe; 53. Liquid level sensor; 54. Check valve; 55. Hydrophobic and breathable component; 56. Three-way valve; 57. Backwash port. Detailed Implementation

[0018] The following is in conjunction with the appendix Figures 1-6 This application will be described in further detail. Example 1

[0019] Example 1 of this application discloses a device for preparing microspherical ceftiofur hydrochloride nanoemulsion injection, referring to... Figure 1 and Figure 2 The apparatus for preparing microsphere ceftiofur hydrochloride nanoemulsion injection includes a sterile tank 1 and a support 2. The sterile tank 1 is disposed on one side of the support 2 and is hollow inside to accommodate the materials to be mixed. In order to facilitate the installation of the sterile tank 1, in this embodiment, the middle section of the sterile tank 1 is preferably a cylindrical section, while the upper and lower ends are tapered conical or frustum sections. The upper conical section has an inlet 11 on its side wall, and the corresponding lower conical section has an outlet 12 on its side wall. The inlet 11 and outlet 12 are used for feeding and discharging, respectively. When mixing in the sterile tank 1, both the inlet 11 and outlet 12 are sealed. The microsphere powder and the dispersing fluid (such as thickener, osmotic pressure regulator, etc.) are introduced into the tank through the inlet 11 in an appropriate amount according to the mixing ratio.

[0020] The support member 2 is placed on the ground and used to install and support the aseptic tank 1. In this embodiment, the support member 2 has a rectangular shape. The support member 2 can be directly fixed to the ground, or it can be equipped with lifting wheels at the bottom. When a fixed position is required, the wheels retract into the support member 2, and only the support member 2 body contacts the ground for support. When a position needs to be moved, the wheels extend to contact the ground and raise the support member 2, at which point the support member 2 can be pushed to the target position.

[0021] The support 2 is provided with a first mounting rack 21 and a second mounting rack 22 on one side, wherein the first mounting rack 21 is preferably a U-shaped support, the U-shaped opening of the first mounting rack 21 faces away from the support 2, the U-shaped middle protruding part of the first mounting rack 21 is rotationally connected with the side wall of the support 2, and the rotation axis is horizontal, the rotation axis of the first mounting rack 21 coincides with the symmetry axis of the U-shaped support itself, and the second mounting rack 22 and the sterile tank body 1 are both mounted at the opening position of the first mounting rack 21, when the first mounting rack 21 rotates around the rotation axis itself, the second mounting rack 22 and the sterile tank body 1 also synchronously rotate around the horizontal axis with the first mounting rack 21. A set of intermeshing reduction gears (not shown) are rotationally connected to the inner wall of the support 2 corresponding to the first mounting rack 21, one reduction gear with a larger diameter is coaxially fixed with the first mounting rack 21 through a rotating shaft, and the reduction gear with a smaller diameter is coaxially fixed with the output shaft of a servo motor (not shown). The servo motor drives the reduction gear with a larger diameter to rotate through the reduction gear with a smaller diameter, and after the reduction of the reduction gear, the servo motor drives the first mounting rack 21 to rotate at a lower speed.

[0022] The second mounting rack 22 is preferably an L-shaped support, which includes a long rod with a longer length and a short rod with a shorter length, the short rod of the second mounting rack 22 is used to be connected with the first mounting rack 21, and the long rod of the second mounting rack 22 is used to be connected with the sterile tank body 1. Specifically, one end of the short rod of the second mounting rack 22 is connected with the inner side wall of one end of the first mounting rack 21 through a transmission gear 221, the transmission gear 221 is provided with two gears with different diameters, and the two transmission gears 221 are intermeshed, and both of the two transmission gears 221 are rotationally connected to the first mounting rack 21, wherein the rotation axis of the transmission gear 221 with a larger diameter is vertical, and one end of the short rod of the second mounting rack 22 is detachably connected to the side wall of the transmission gear 221 with a larger diameter, and the detachable connection mode can be preferably bolted. The first mounting rack 21 is also fixed with a driving motor 211, the output shaft of the driving motor 211 penetrates through the first mounting rack 21 and is coaxially fixed with the transmission gear 221 with a smaller diameter. One end of the long rod of the second mounting rack 22 is fixedly connected with the side wall of the conical section of the upper end of the sterile tank body 1, and the other end of the sterile tank body 1 away from the second mounting rack 22 is hingedly connected with the inner side wall of the other end of the first mounting rack 21 through a universal joint or a spherical bearing seat, and the axis of the sterile tank body 1 is eccentrically arranged relative to the common vertical rotation axis of the second mounting rack 22.

[0023] When the first mounting frame 21 rotates while the second mounting frame 22 remains stationary, the first mounting frame 21 can drive the second mounting frame 22 and the sterile tank 1 to rotate around the horizontal axis, at this time the sterile tank 1 is like a bottle fixed on the U-shaped support, and the U-shaped support makes slow up-down rolling movement together, in the process of up-down rolling, the material in the sterile tank 1 will flow back and forth in the vertical direction under the action of its own gravity to realize the mixing of the material. When the second mounting frame 22 drives the sterile tank 1 to rotate while the first mounting frame 21 remains stationary, since the rotation axis of the second mounting frame 22 is vertical, the sterile tank 1 will also rotate around this vertical rotation axis, and since there is an inclined angle between the axis of the sterile tank 1 and the rotation axis of the second mounting frame 22, that is, the sterile tank 1 is eccentrically arranged, the second mounting frame 22 will push and pull one end of the sterile tank 1 to make circular motion like a crank, while the other end of the sterile tank 1 is constrained by the spherical bearing seat and can only swing within a certain range, resulting in that the sterile tank 1 will make horizontal conical shaking around the vertical rotation axis. Finally, combined with the rotation of the first mounting frame 21 around the horizontal axis and the rotation of the second mounting frame 22 around the vertical axis, and the first mounting frame 21 and the second mounting frame 22 can be set to different, non-integer ratio of rotational speed according to the actual working condition (for example, the rotational speed of A shaft is 10 rpm, and the rotational speed of B shaft is 7 rpm), the sterile tank 1 will follow the first mounting frame 21 to roll up and down, and at each moment of rolling, the eccentric rotation of the sterile tank 1 around the vertical rotation axis will exert a transverse, circular pushing force on the sterile tank 1, which means that the direction of the transverse pushing force and the posture of the sterile tank 1 are always different at the same position in space, and the motion trajectory of the sterile tank 1 is no longer a simple superposition of "rolling + shaking", but a complex, chaotic and never-repeating "space 8-shaped dance". The motion trajectory of any point on the sterile tank 1 in three-dimensional space is a seemingly chaotic but precisely controlled curve, so that the sterile tank 1 makes three-dimensional compound motion in space. It is this never-repeating motion trajectory that makes the material in the sterile tank 1 be stirred from all directions and angles, and any area that may settle due to gravity or centrifugal force will be broken and washed away by the new motion posture at the next moment. The sterile tank 1 can also be integrally formed with helical flow guide ribs or grooves on the inner wall, so that the material slowly spirals while rolling, realizing true global mixing. At the same time, there is no high-speed component in the whole mixing process, and the motion speed of the sterile tank 1 is controllable and low, like shaking a bottle with the wrist and arm, so the action is smooth and soft, which can effectively protect the microsphere structure from being damaged during the mixing process.

[0024] Further, with reference to Figure 3 and Figure 4The inside of the aseptic tank body 1 is provided with an agitating disc 3 and a guide column 13, wherein the guide column 13 is arranged along the axis of the aseptic tank body 1, and the two ends are fixedly connected with the inner wall of the aseptic tank body 1, the outer wall of the guide column 13 is provided with a spiral guide groove 131 along the axis, the inner wall of the agitating disc 3 is integrally formed with a protrusion (not shown) matched with the spiral guide groove 131, and the protrusion is correspondingly and slidingly connected in the spiral guide groove 131 of the guide column 13, so that the agitating disc 3 can rotate synchronously when moving along the axis of the guide column 13. Specifically, the agitating disc 3 comprises an agitating base 31 and a plurality of agitating rings 32, the agitating base 31 and the agitating rings 32 are concentrically arranged, and the agitating base 31 is concentrically sleeved on the outer wall of the guide column 13, the protrusion matched with the spiral guide groove 131 is integrally formed on the inner wall of the agitating base 31, and the protrusion is correspondingly and slidingly connected in the spiral guide groove 131 of the guide column 13, so that the agitating base 31 can move along the axis of the guide column 13 while rotating synchronously around the guide column 13. In the embodiment 1 of the present application, the agitating rings 32 are preferably two, the diameters of the two agitating rings 32 gradually increase, so that a gap is left between the two agitating rings 32 for the liquid to pass through, and the two agitating rings 32 are concentrically arranged outside the agitating base 31, the two agitating rings 32 are fixedly connected by a plurality of connecting rods, and the agitating ring 32 located in the innermost circle is also fixedly connected with the agitating base 31 by a plurality of connecting rods, so that the two agitating rings 32 and the central agitating base 31 form a whole body moving together.

[0025] A plurality of through holes for the liquid to pass through are provided on the agitating base 31, and a plurality of counterweights (not shown) are symmetrically embedded in the agitating base 31 relative to the rotation axis, so as to appropriately increase the weight of the agitating base 31, so that the agitating base 31 is more easily moved along the guide column 13 by its own gravity, and the agitating base 31 as a whole is in the shape of a flat body spindle with a larger diameter in the middle and smaller diameters at both ends, and the surface of the agitating base 31 is a smooth transition curved surface, so that the agitating base 31 is less resistant when moving in the liquid. Similarly, the two end faces of the two agitating rings 32 along the axis of the guide column 13 are also smooth transition curved surfaces, and the spiral flow guide ribs can be integrally formed on the side wall of the agitating ring 32, so that the agitating ring 32 can further stir the material when rotating in the aseptic tank body 1. In order to reduce the damage to the inner wall of the aseptic tank body 1, the agitating ring 32 and the agitating base 31 are preferably made of medical PEEK (polyether ether ketone) material, so that the surface of the agitating ring 32 and the agitating base 31 is smooth, effectively reducing the friction between the agitating ring 32 and the aseptic tank body 1, the agitating base 31 and the guide column 13, prolonging the service life of the agitating ring 32 and the agitating base 31, and also meeting the requirements of USP Class VI (United States Pharmacopoeia Convention).

[0026] When the aseptic tank body 1 is flipped up and down with the first mounting frame 21, the stirring disc 3 slides up and down along the guide column 13 by gravity, and the stirring base 31 rotates the two stirring rings 32 together around the guide column 13 while sliding, and the stirring disc 3 can stir the material up and down and spirally by the two concentric stirring rings 32 when sliding up and down along the guide column 13. Since the stirring base 31 is also provided with a plurality of through holes, the liquid material will form a turbulent flow after passing through the through holes on the stirring base 31 when moving up and down and rotating, further stirring the material. This process does not require any driving source, and the stirring of the stirring disc 3 to the material completely relies on the flipping action of the aseptic tank body 1 in space, which can further mix the material in the aseptic tank body 1.

[0027] Further, the aseptic tank body 1 is also provided with a sampling tube 4, and the stirring base 31 is coaxially rotated with a limiting seat 33 at one end surface near the feed inlet 11 of the aseptic tank body 1. The inner wall of the limiting seat 33 is in sliding connection with the outer wall of the guide column 13, and the limiting seat 33 has a smooth transition curved surface on the surface like the stirring base 31, which can reduce the resistance when moving in the liquid. When the stirring base 31 rotates relative to the guide column 13, the limiting seat 33 does not rotate, but only moves along the axis of the guide column 13. In the embodiment 1 of the present application, the sampling tube 4 is preferably a telescopic sampling tube 4 formed by mutually sleeving a plurality of hollow tubes, and the end of the hollow tube with a smaller inner diameter between the adjacent two hollow tubes constituting the sampling tube 4 is sleeved with a thin sealing rubber ring (not shown). When the hollow tube with a smaller diameter slides in the adjacent hollow tube with a larger diameter, the sealing rubber ring can effectively reduce the leakage of liquid and also effectively reduce the friction between the hollow tubes. The number of hollow tubes can be determined according to the specific stroke of the stirring disc 3. The end of the hollow tube with the smallest diameter in the sampling tube 4 is inserted into the limiting seat 33 and then diverges out of the limiting seat 33. When the stirring disc 3 moves along the axis of the guide column 13, the stirring base 31 drives the sampling tube 4 with the smallest diameter to move synchronously through the limiting seat 33. In this process, the sampling tube 4 will expand and contract according to the movement of the stirring base 31. In the embodiment of the present application, the sampling tube 4 is preferably provided with 4 groups, and the 4 groups of sampling tubes 4 are distributed at intervals around the guide column 13, and the axis of each group of sampling tubes 4 is parallel to the axis of the guide column 13.

[0028] Referring to Figures 3 to 6The other end of the sampling tube 4 penetrates out of the aseptic tank body 1 near one end of the second mounting frame 22, and the aseptic tank body 1 is fixed with a closed bin 5 on the outer wall of the end where the sampling tube 4 penetrates out, and the side wall of the closed bin 5 is detachably connected with the side wall of the second mounting frame 22, and the detachable connection mode can also be bolted connection, which facilitates the disassembly and assembly of the closed bin 5. The closure cover is arranged at the end of the aseptic tank body 1, and the mounting seat 14 is fixed on the outer wall of the aseptic tank body 1 corresponding to the closure cover of the closed bin 5, one end of the sampling tube 4 is inserted into the mounting seat 14, and the mounting seat 14 and the closed bin 5 are sealed and connected through aseptic sealing ring and the like, so that the internal space of the closed bin 5 is kept in a sealed state during work. The closed bin 5 is provided with a suction member 51 and a sample collection bin 52, wherein the suction member 51 is fixed in the closed bin 5 through a support, and can be preferably a micro vacuum pump, and the sample collection bin 52 corresponds to the sampling tube 4 one by one, so that in the embodiment of the application, the sample collection bin 52 is provided with four, and the suction port of the suction member 51 is communicated with the outlet of the sample collection bin 52 through a connection main pipe provided with four branch pipes, and the four branch pipes of the connection main pipe correspond to one sample collection bin 52 respectively. The inlet of the sample collection bin 52 is communicated with the sampling tube 4, so that the suction member 51 can vacuumize the sample collection bin 52, so that the mixed material in the aseptic tank body 1 enters the sample collection bin 52 through the sampling tube 4 for collection, thereby realizing sampling. In order to monitor that the amount of the sample collected in the sample collection bin 52 does not exceed the specified amount in real time, the closed bin 5 is further provided with a liquid level sensor 53, which is preferably an ultrasonic liquid level sensor 53, and the liquid level sensor 53 is fixed in the closed bin 5 through a mounting bracket, and the liquid level sensor 53 corresponds to the sample collection bin 52 one by one, and the liquid level sensor 53 is tightly attached to the outer wall of the sample collection bin 52 near one end of the suction member 51. The outside of the closed bin 5 is provided with a PLC control unit (not shown), and the driving motor 211, the suction member 51 and the liquid level sensor 53 are electrically connected with the control unit, when the liquid level sensor 53 detects that the amount of the sample collected in the sample collection bin 52 meets the requirements, the liquid level sensor 53 sends a signal to the control unit, and the control unit immediately sends a stop instruction to the suction member 51, that is, the extraction of the sample can be stopped.

[0029] Further, to prevent the liquid in the sample collection chamber 52 from flowing back into the sterile tank 1 after the suction member 51 stops vacuumizing and balancing the air pressure, a medical micro-check valve 54 is connected between the sample collection chamber 52 and the corresponding sampling tube 4, the check valve 54 allows the material to enter the sample collection chamber 52 through the sampling tube 4, and prevents the material in the sample collection chamber 52 from flowing back into the sterile tank 1, a slot is formed on the mounting seat 14 to accommodate the check valve 54, and the check valve 54 is clamped and fixed on the mounting seat 14. To facilitate the extraction of the sample in the sample collection chamber 52, a detection branch pipe 521 is connected to the side wall of the sample collection chamber 52 near one end of the check valve 54, the detection branch pipe 521 can be a self-sealing medical catheter, and the end of the detection branch pipe 521 away from the sample collection chamber 52 penetrates out of the closed chamber 5 and is in a self-sealing state, when the sample needs to be extracted, only a corresponding syringe or a thinner extraction tube needs to be inserted into the end of the detection branch pipe 521, and the detection sample in the sample collection chamber 52 can be extracted through the detection branch pipe 521.

[0030] To prevent the liquid drawn from the sterile tank 1 from entering the suction member 51 and the sample collection chamber 52, a hydrophobic air permeable member 55 is arranged between the suction member 51 and the sample collection chamber 52, the hydrophobic air permeable member 55 includes a hydrophobic filter membrane and two sealing clamps, the two sealing clamps are symmetrically sealed and clamped to form a whole, the hydrophobic filter membrane is located between the two sealing clamps, the two sealing clamps fix the hydrophobic filter membrane in the middle after being sealed and clamped, and the two sealing clamps are respectively connected to the outlet of the sample collection chamber 52 and the branch pipe corresponding to the connection main pipe, the hydrophobic filter membrane in the hydrophobic air permeable member 55 allows airflow but blocks liquid, effectively preventing liquid from being sucked into the suction member 51 when the sample is extracted. Further, a micro-electrically controlled three-way valve 56 is arranged between the check valve 54 and the corresponding sampling tube 4, the three-way valve 56 is directly embedded and fixed inside the mounting seat 14 and is also electrically connected with the control unit, two interfaces of the three-way valve 56 are respectively connected with the check valve 54 and the sampling tube 4, and the last interface can be used to externally connect a special cleaning device or a sealed condenser tank, to facilitate subsequent cleaning of the sampling tube 4 and the sample collection chamber 52 or to prevent open discharge during the cleaning process. A backflushing interface 57 is connected to the branch pipe of the corresponding connection main pipe between the hydrophobic air permeable member 55 and the suction member 51, and a medical catheter in a self-sealing state is also connected to the backflushing interface 57, one end of the medical catheter connected to the backflushing interface 57 also penetrates out of the closed chamber 5 and can be externally connected to a blowing device for cleaning. In other embodiments of the present application, the closed chamber 5 can preferably be appropriately enlarged in volume, and a small-sized power supply module (not shown) is integrated in the closed chamber 5, the power supply module supplies power to the electrical components in the closed chamber 5, such as valves, sensors and the like, which have small power consumption, thereby reducing the wiring of the whole sterile tank 1, of course, the power supply module can be directly fixed on the outer wall of the sterile tank 1 when necessary.

[0031] When the sterile tank 1 is flipped up and down by the first mounting frame 21, the stirring disc 3 in the sterile tank 1 rotates as a whole while sliding along the guide column 13 by its own gravity, and the sampling tube 4 with the smallest diameter end (i.e. the sampling port) can follow the stirring disc 3 reciprocating along the guide column 13 axis, and the specific sampling time interval can be adjusted by the control software written by the PLC control unit. Within the preset sampling time interval, the position where the sampling end of the sampling tube 4 stays is random, so that the sampling tube 4 can sample the material in the sterile tank 1 at a random position, greatly improving the randomness of sampling. In this process, the sampling tube 4 performs corresponding extension and retraction movement, and the other end of the sampling tube 4 penetrates out of the sterile tank 1 and communicates with the sample collection bin 52, and the outlet of the sample collection bin 52 is connected with the suction member 51. When the sterile tank 1 is mixed for a predetermined time, the suction member 51 vacuums the sample collection bin 52, so that a negative pressure is generated in the sample collection bin 52. The mixed material in the sterile tank 1 enters the sample collection bin 52 through the three-way valve 56 and the check valve 54 under the action of atmospheric pressure, realizing the collection of the sample. In this process, due to the presence of the hydrophobic filter membrane in the hydrophobic air-permeable member 55, the sample extracted into the sample collection bin 52 is blocked by the hydrophobic filter membrane, avoiding the liquid sample from being sucked into the suction member 51. When the liquid level sensor 53 detects that the amount of the sample collected in the sample collection bin 52 reaches a threshold value, the control unit sends an instruction to stop the suction member 51 from working. The suction member 51 exhausts the air to balance the air pressure in the pipeline between the sample collection bin 52 and the suction member 51, and the sample is cut off by the check valve 54 and remains in the sample collection bin 52 for preservation. At this time, the three-way valve 56 used as the interface of external equipment can be connected to a sealed condensing tank. During the process of re-flipping the closed bin 5 to the top of the sterile tank 1, the three-way valve 56 is connected to the condensing tank and the interface of the sampling tube 4 is opened, balancing the air pressure between the sampling tube 4 and the sterile tank 1, and part of the liquid remaining in the sampling tube 4 flows back to the sterile tank 1. The condensing tank connected to the three-way valve 56 can receive part of the backflow liquid to prevent liquid from flowing out of the sterile tank and causing pollution. After the mixing is stopped, the user can extract the sample in the sample collection bin 52 through the detection branch pipe 521 for mixing degree detection.

[0032] When the material is mixed and the sterile tank 1 needs to be cleaned, the mixed material in the tank is first discharged, the first mounting frame 21 is rotated, the closed chamber 5 is kept in the posture above the sterile tank 1, one of the three-way valves 56 is connected with the interface of the external equipment and the cleaning liquid suction pump, the suction pump connects the cleaning liquid along the interface of the three-way valve 56, the three-way valve 56 is first opened to connect the interface of the corresponding check valve 54 and closed to connect the interface of the sampling pipe 4, the cleaning liquid enters the corresponding sample collection chamber 52 through the three-way valve 56 and the check valve 54, at this time, the cleaning liquid can flush the inside of the sample collection chamber 52, at this time, the detection branch pipe 521 can be connected with a sealed waste liquid collection tank, the waste liquid after cleaning flows out of the sample collection chamber 52 along the detection branch pipe 521; after cleaning the sample collection chamber 52, the interface of the three-way valve 56 and the corresponding check valve 54 is closed and the interface of the corresponding sampling pipe 4 is opened, so that the cleaning liquid flows into the sterile tank 1 along the sampling pipe 4, which can clean the inner wall of the sterile tank 1, and the waste liquid after cleaning can be discharged through the discharge port 12. After sufficient cleaning, stop the cleaning liquid, connect the interface of the three-way valve 56 with the sealed condensation tank, at this time, use the backwashing interface 57 to connect the gas pipe supplying nitrogen or steam, and clean dry nitrogen or high-temperature steam is supplied into the sample collection chamber 52 through the backwashing interface 57, when the nitrogen or steam passes through the hydrophobic filter membrane of the hydrophobic air permeable part 55, the hydrophobic filter membrane can be backwashed and cleaned, then the nitrogen or steam enters the sample collection chamber 52 to clean the sample collection chamber 52, the three-way valve 56 can sequentially open the interfaces of the connected condensation tank and sampling pipe 4, so that the nitrogen or steam can flow out of the sample collection chamber 52 along the detection branch pipe 521, or flow into the sterile tank 1 along the sampling pipe 4, to clean the sampling pipe 4 and the sterile tank 1. The cleaning operation includes cleaning liquid cleaning and nitrogen cleaning, which can be sequentially performed on all sample collection chambers 52, until the cleaning operation is completed on all sample collection chambers 52 and all sampling pipes 4.

[0033] Now, one of the working scenes that may occur in the actual mixing process is described by framing the parameters of each component: 5ml is taken from each sample collection chamber 52, the volume of the sample collection chamber 52 is 6ml, including 5ml working volume and 1ml dead volume, the shape of the sample collection chamber 52 is cylindrical (diameter 20mm, height 20mm), the sample collection chamber 52 can be preferably made of borosilicate glass material, the inlet and outlet of the sample collection chamber 52 are double-clamp quick-connecting, which is convenient for disassembly and assembly.

[0034] According to the sampling requirements of GMP, 4 times of sampling, each 5 mL, total sampling amount 20 mL, total sampling amount should account for 0.303% of the total amount of mixed material, so the total amount of mixed liquid is about 6.6 L (6600 mL), in order to ensure the effect of overturning mixing, according to the standard of pharmaceutical equipment that the liquid filling rate is 60-70%, the liquid filling rate is 65%, so the total volume of sterile tank 1 is: 6.6L / 0.65≈10.15L, so a standard 10L tank is taken. Verify the actual size of sterile tank 1, take the middle cylindrical section of sterile tank 1, diameter D=0.22m, height H=0.26m, volume V1=π×(0.11)²×0.26≈9.0L, take the height of the conical section at both ends h=0.1m, volume V2=(1 / 3)×π×(0.11)²×0.1≈1.27L, total volume=9.0+2×1.27=11.54L>10L (safety).

[0035] Regarding the parameters of the stirring disc 3, according to the shear force formula: τ = μ × (ω r / δ) target τ < 10 Pa, take μ = 0.01 Pa·s (water phase), r = 0.08 m, δ = 0.0002 m, get the maximum speed of stirring disc 3 ωmax=25 rad / s≈240 rpm, the actual working speed is 120 rpm, which meets the target speed value of 50-150 rpm. The stirring disc 3 is made of uniform material (i.e. the main body is made of medical PEEK), the overall density of the stirring disc 3 is 1.3 g / cm³, the maximum diameter is 0.16 m, the thickness is 0.01 m, the final mass m≈0.26 kg, the actual final mass of the stirring disc 3 can be adjusted according to the embedded weight block, so that the stirring disc 3 as a whole can reach the target speed, and will not damage the microspheres in the material.

[0036] The speed of the stirring disc 3 moving along the guide column 13 is verified, the target rotating speed is 12.57 rad / s (120 rpm), the inclination angle of the guide column 13 is 30°, the helix guide groove 131 on the guide column 13 has a helix lead angle of 25°, a safety margin of +5° is reserved for the friction angle, the diameter of the guide column 13 is 0.02 m, the lead is 0.15 m, and the theoretical rotating speed is calculated to be 13.2 rad / s (126 rpm), which is verified to meet the standard. Considering the actual friction, the material combination of the helix guide groove 131 and the protrusion on the inner wall of the stirring disc 3 is 316L (stainless steel) + zirconia ceramic, the actual dynamic friction coefficient μ is 0.12, the compensation measure is to increase the helix guide groove 131 lead angle by 3°, so the corrected actual lead angle is 28°, and the corrected actual lead is 0.17 m. The parameters of the stirring system are matched, the tank body rotating speed is first mounting bracket 21: 5 rpm (horizontal axis), second mounting bracket 22: 3 rpm (vertical axis), and the relative rotating speed of the stirring disc 3 is: average 126 rpm, instantaneous fluctuation ± 5%.

[0037] The three-way valve 56 has a Cv of 1.5, a response time of <0.1 s, and a fluid pressure drop loss of 0.02 bar after passing through; the check valve 54 has an opening pressure difference of 0.05 bar, the hydrophobic filter membrane has a pore size of 0.2 μm, a gas permeability of 150 L / min, and a fluid pressure drop loss of 0.01 bar after passing through. When the vacuum pump is pumping the sample, the sample time target is: 5 mL / 5 s = 1 mL / s, the total pumping volume including the pipeline expansion volume is 10 mL, the total pumping volume is 15 mL / 5 s, the theoretical flow rate is: 0.3 L / min, therefore a micro diaphragm vacuum pump is selected, the actual flow rate is 0.5 L / min > 0.3 L / min, the power is 40 W, the hydrophobic filter membrane has a double-layer filter membrane structure, the main filter membrane is 0.2 μm ePTFE (expanded polytetrafluoroethylene), the support layer is 316L sintered metal (pore size 10 μm, thickness 1 mm), and the installation adopts edge laser welding + center hydraulic expansion.

[0038] The working parameters of the above-mentioned components are only for verifying the feasibility of the working flow of the entire mixing device, ensuring that the device can operate normally and achieve the preset mixing effect, and the specific working parameters of the actual components can be adjusted according to the actual working requirements, such as the sample volume and the volume of the sterile tank 1, the selection and parameters of the components, and the final size can be adjusted according to the actual working conditions.

[0039] The implementation principle of the microspherical cefetamet pivoxil hydrochloride nanoemulsion injection preparation device of the embodiment 1 is that the sterile tank body 1 rolls up and down with the first mounting frame 21, and in each moment of rolling, the eccentric rotation of the sterile tank body 1 around the vertical rotation shaft applies a transverse and circumferential thrust to the sterile tank body 1, which means that the transverse thrust direction and posture of the sterile tank body 1 are always different when it is in the same position in space. It is this never-repeated motion track that makes the materials in the sterile tank body 1 be stirred from all directions and at all angles. Any area that may be settled due to gravity or centrifugal force will be broken and washed by the new motion posture in the next moment. The motion speed of the sterile tank body 1 is controllable and low, like shaking a bottle with the wrist and arm, so the motion is continuous and soft, which can effectively protect the microsphere structure from being damaged during mixing. When the stirring disc 3 slides up and down along the guide column 13, it can stir the material up and down and spirally by relying on the two concentric stirring rings 32. This process does not require any driving source. The stirring of the material by the stirring disc 3 completely relies on the turning action of the sterile tank body 1 in space, which can further mix the materials in the sterile tank body 1. When mixing the materials, the stirring disc 3 can also drive the sampling tube 4 to randomly sample in the sterile tank body 1, greatly improving the randomness of sampling and effectively improving the accuracy of sampling detection. Embodiment 2

[0040] The embodiment 2 provides a microspherical cefetamet pivoxil hydrochloride nanoemulsion injection production process. The microspherical cefetamet pivoxil hydrochloride nanoemulsion injection is produced by using the microspherical cefetamet pivoxil hydrochloride nanoemulsion injection preparation device as described in the embodiment 1, and includes the following steps. S1: uniformly dispersing water-soluble cefetamet pivoxil hydrochloride in an oil phase to form a stable nanoemulsion, using biodegradable polylactic acid-glycolic acid copolymer high molecular material to wrap the nanoemulsion prepared in the previous step to form a microsphere, collecting the formed microsphere by centrifugation or filtration, repeatedly washing the microsphere with purified water to remove residual organic solvents and surfactants, and finally obtaining dry microsphere powder by freeze-drying; S2: injecting a certain amount of microsphere powder and a dispersion medium fluid into the sterile tank body 1 through the feeding port 11, then closing the feeding port 11, respectively starting the first mounting frame 21 and the second mounting frame 22, rotating the sterile tank body 1 relative to the first mounting frame 21 together with the second mounting frame 22, and making the sterile tank body 1 perform inclined eccentric rotation relative to the rotation axis of the second mounting frame 22, while the first mounting frame 21 rotates around its own axis to drive the second mounting frame 22 and the sterile tank body 1 to rotate together, the superimposed motion of the first mounting frame 21 and the second mounting frame 22 rotating around their own axes makes the sterile tank body 1 perform slow and irregular three-dimensional compound motion in space, and the materials in the sterile tank body 1 move irregularly and are mixed sufficiently under the action of gravity. S3: After mixing, the material in the sterilized tank 1 is sampled and detected, and after passing the detection, the material is sterilized and filled.

[0041] The above are preferred embodiments of the present application, and do not limit the protection scope of the present application, so: any equivalent changes made according to the structure, shape, principle of the present application should be covered within the protection scope of the present application.

Claims

1. A device for preparing microspherical ceftiofur hydrochloride nanoemulsion injection, characterized in that: include The aseptic tank (1) is used to hold the materials to be mixed. One end of the aseptic tank (1) is provided with an inlet (11) and the other end is provided with an outlet (12). Support (2) is used to place on the ground and install support for sterile tank (1). A first mounting frame (21) and a second mounting frame (22) are provided on one side of the support (2). The first mounting frame (21) is rotatably connected to the support (2), and the second mounting frame (22) is rotatably connected to the first mounting frame (21). The rotation axes of the first mounting frame (21) and the second mounting frame (22) are perpendicular to each other. The sterile tank (1) is fixedly connected to the second mounting frame (22), and the axis of the sterile tank (1) itself is eccentrically set relative to the rotation axis of the second mounting frame (22). While the sterile tank (1) rotates with the second mounting frame (22), the sterile tank (1) also rotates around the rotation axis of the first mounting frame (21) so that the sterile tank (1) makes a three-dimensional composite motion in space. A stirring plate (3) is installed inside the sterile tank (1). The stirring plate (3) can move back and forth along the axis of the sterile tank (1) by its own weight to actively mix and stir the materials inside the sterile tank (1).

2. The apparatus for preparing microspherical ceftiofur hydrochloride nanoemulsion injection according to claim 1, characterized in that: The first mounting bracket (21) is a U-shaped bracket. The U-shaped opening of the first mounting bracket (21) faces away from the support member (2). The rotation axis of the first mounting bracket (21) is horizontal and coincides with the axis of symmetry of the U-shaped bracket. The protruding part of the U-shaped middle section of the first mounting bracket (21) is rotatably connected to the support member (2). The second mounting bracket (22) and the sterile tank (1) are both located at the opening position of the first mounting bracket (21).

3. The apparatus for preparing microspherical ceftiofur hydrochloride nanoemulsion injection according to claim 2, characterized in that: The second mounting bracket (22) is an L-shaped bracket. One end of the second mounting bracket (22) is rotatably connected to the inner wall of one end of the first mounting bracket (21). The other end of the second mounting bracket (22) is fixedly connected to one end of the sterile tank (1). The end of the sterile tank (1) away from the second mounting bracket (22) is hinged to the other end of the first mounting bracket (21). The sterile tank (1) and the second mounting bracket (22) rotate synchronously relative to the first mounting bracket (21) as a whole. The axis of the sterile tank (1) itself is eccentrically set relative to the common axis of rotation of the sterile tank (1) and the second mounting bracket (22).

4. The apparatus for preparing microspherical ceftiofur hydrochloride nanoemulsion injection according to claim 1, characterized in that: The sterile tank (1) is provided with a guide column (13) inside. The guide column (13) is arranged along the axial direction of the sterile tank (1). The outer wall of the guide column (13) is provided with a spiral guide groove (131) along its own axial direction. The inner wall of the stirring plate (3) is slidably connected to the spiral guide groove (131) so that the stirring plate (3) can rotate synchronously when it moves along the axial direction of the guide column (13).

5. The apparatus for preparing microspherical ceftiofur hydrochloride nanoemulsion injection according to claim 4, characterized in that: The mixing plate (3) includes a mixing base (31) and multiple mixing rings (32). The mixing base (31) is coaxially arranged with the guide post (13) and slidably connected to the guide post (13). Multiple through holes are opened on the mixing base (31). The diameter of the multiple mixing rings (32) gradually increases and they are concentrically distributed on the outer ring of the mixing base (31). The multiple mixing rings (32) are fixedly connected to each other. The innermost mixing ring (32) is fixedly connected to the mixing base (31).

6. The apparatus for preparing microspherical ceftiofur hydrochloride nanoemulsion injection according to claim 5, characterized in that: The stirring base (31) is provided with a retractable sampling tube (4). One end of the sampling tube (4) passes through the stirring base (31) and extends outwards. The other end of the sampling tube (4) passes out of the sterile tank (1) near the second mounting bracket (22). The sampling tube (4) moves along the axis of the sterile tank (1) with the stirring base (31). The sterile tank (1) is provided with a suction component on the outer wall of the end through which the sampling tube (4) passes. The suction component can extract the material in the sterile tank (1) through the sampling tube (4) to achieve sampling.

7. The apparatus for preparing microspherical ceftiofur hydrochloride nanoemulsion injection according to claim 6, characterized in that: The suction assembly includes a sealed closed chamber (5), the sealed chamber (5) is sealed at the end of the sterile tank (1), the closed chamber (5) is provided with a suction component (51) and a sample collection chamber (52), the outlet of the sample collection chamber (52) is connected to the suction component (51), the inlet of the sample collection chamber (52) is connected to the sampling tube (4), a check valve (54) is provided between the sample collection chamber (52) and the sampling tube (4) to allow the material to enter the sample collection chamber (52) through the sampling tube (4), the side wall of the sample collection chamber (52) near the sampling tube (4) is connected to a detection branch pipe (521), the end of the detection branch pipe (521) away from the sample collection chamber (52) extends out of the closed chamber (5) and is in a self-sealing state.

8. The apparatus for preparing microspherical ceftiofur hydrochloride nanoemulsion injection according to claim 7, characterized in that: A hydrophobic and breathable component (55) is provided between the suction component (51) and the sample collection chamber (52). The hydrophobic and breathable component (55) allows airflow to pass through while blocking liquid. A three-way valve (56) is also provided between the check valve (54) and the sampling tube (4). Two of the ports of the three-way valve (56) are connected to the check valve (54) and the sampling tube (4) respectively. The last port is used to connect to an external cleaning device. A backwashing port (57) is provided in the pipeline between the hydrophobic and breathable component (55) and the suction component (51). The backwashing port (57) is in a self-sealing state.

9. A manufacturing process for microspherical ceftiofur hydrochloride nanoemulsion injection, characterized in that: The preparation of the injection solution using the microsphere ceftiofur hydrochloride nanoemulsion preparation apparatus as described in any one of claims 1-8 includes the following steps: S1: Water-soluble ceftiofur hydrochloride is uniformly dispersed in the oil phase to form a stable nano-scale emulsion. A biodegradable polylactic acid-glycolic acid copolymer polymer material is used to encapsulate the nano-emulsion prepared in the previous step to form micron-scale spheres. The formed microspheres are collected by centrifugation or filtration, and repeatedly washed with purified water to remove residual organic solvents and surfactants. Finally, the dried microsphere powder is obtained by freeze drying. S2: A quantitative amount of microsphere powder and dispersion medium fluid are injected together through the feed port (11) of the sterile tank (1), and then the feed port (11) is closed. The first mounting frame (21) and the second mounting frame (22) are started respectively. The sterile tank (1) rotates relative to the first mounting frame (21) along with the second mounting frame (22). The sterile tank (1) rotates eccentrically relative to the axis of rotation of the second mounting frame (22). At the same time, the first mounting frame (21) rotates around its own axis, which drives the second mounting frame (22) and the sterile tank (1) to rotate together. The superimposed motion of the first mounting frame (21) and the second mounting frame (22) rotating around their own axes respectively makes the sterile tank (1) make a slow and irregular three-dimensional composite motion in space. The material inside the sterile tank (1) moves irregularly under the action of gravity and is gently and thoroughly mixed. S3: After mixing, sample the material in the aseptic tank (1) for testing. If the material passes the test, aseptically fill it.

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