Mitomycin freeze-dried powder and preparation equipment thereof

Abstract

This invention provides mitomycin freeze-dried powder with excellent solubility and stability, as well as equipment for preparing the same. [Solution] In step 1, the raw materials are sieved through a 200-mesh sieve in preparation for use; in step 2, approximately 60% of the prescribed amount of sterile water for injection is weighed into a liquid mixing tank and the sterile water for injection is cooled to 1-5°C; in step 3, the prescribed amount of mannitol powder is added to the liquid mixing tank; in step 4, the prescribed amount of mitomycin is dispersed in an isolator with an appropriate amount of sterile water for injection and then added to the liquid mixing tank, the liquid mixing tank is started and stirred until completely dissolved; in step 5, the sterile water for injection is replenished to the full volume, the temperature of the drug solution is maintained at 1-5°C and stirred continuously; and in step 6, the temperature of the liquid mixing tank is maintained at -2-2°C, and it is filtered online and filled.

Description

Technical Field

[0001] The present invention relates to the field of preparing mitomycin lyophilized powder, and particularly to mitomycin lyophilized powder and its preparation equipment.

Background Art

[0002] Mitomycin is an effective anti-cancer drug and is used to treat multiple types of cancers. Before preparing mitomycin lyophilized powder, it is necessary to first prepare a mitomycin solution, and then use the mitomycin solution to prepare the lyophilized powder. When preparing a conventional mitomycin solution, it is usually necessary to add an excipient to improve the stability of mitomycin. Due to the characteristics of the excipient, the prepared lyophilized powder may have disadvantages such as poor solubility, insufficient stability, poor performance in the lyophilization process, high cost, and complex quality control.

[0003] In the process of preparing the mitomycin solution, it is necessary to always pay attention to the temperature in the mixing container. If the temperature in the mixing container is too high, it will destroy the molecular structure of mitomycin, cause the invalidation of mitomycin, and further affect the quality of the finished product (mitomycin solution). On the other hand, in the kneading process of preparing the mitomycin solution, the blade contacts and rubs against the kneading solution to generate heat, and the viscosity of the kneading solution in the mixing container gradually increases. If the rotation speed of the blade is fast, the heat generated by the blade and the kneading solution gradually increases, causing the temperature in the mixing container to be too high, and further affecting the quality of the finished product. If the rotation speed of the blade is slow, the kneading time of mitomycin is extended, the preparation efficiency of the mitomycin solution is reduced, and the viscosity state of the solution in the mixing container changes in real time and is difficult to monitor during the kneading process. Therefore, in order to prevent excessive heat generation, a low rotation speed is maintained for the blade, thereby affecting the kneading efficiency of the solution.

Summary of the Invention

Problems to be Solved by the Invention

[0004] Conventional mitomycin freeze-dried powders may have drawbacks such as poor solubility, insufficient stability, poor expression during the freeze-drying process, high cost, and complex quality control, due to the properties of their excipients. To address these issues, the present invention provides a mitomycin freeze-dried powder with adjustable rotation speed and equipment for preparing the same. [Means for solving the problem]

[0005] The technical solution is as follows: Mitomycin freeze-dried powder, prepared in the following quantities, Mitomycin: 1.5-5 mg / ml Mannitol powder: 15-100 mg / ml L-serine: 1.7-6 mg / ml tert-butyl alcohol: 0.2~0.5 ml / ml Potassium dihydrogen phosphate: 3.7-9 mg / ml Potassium hydroxide: Prepare to pH 8-9, Water for injection: Replenish to volume, The production steps for the mitomycin freeze-dried powder are specifically as follows: In Step 1, the raw materials are sieved through a 200-mesh sieve to prepare them for use. In step 2, approximately 60% of the prescribed amount of sterile water for injection is weighed into a liquid mixing tank, and the sterile water for injection is cooled to a temperature of 1-5°C. In step 3, add the prescribed amount of mannitol powder to the liquid mixing tank. In step 4, the prescribed amount of mitomycin is dispersed in an appropriate amount of sterile water for injection in the isolator, then added to the liquid mixing tank, and the liquid mixing tank is started and stirred until completely dissolved. In step 5, replenish the water for injection to its full volume, maintain the temperature of the drug solution at 1-5°C, and continue stirring. In step 6, the liquid mixing tank is temperature-controlled to -2 to 2°C, filtered online, and filled.

[0006] A apparatus for preparing mitomycin freeze-dried powder, comprising a rack to which a stirring case is fixed, a cover fixed to one side of the stirring case away from the rack, the cover provided with a water supply pipe and an exhaust pipe for communication with an external vacuum pump, a discharge pipe provided to one side of the stirring case away from the cover, the stirring case and the cover both being rotatably connected to a rotating shaft, sleeves provided on the rotating shaft at equidistant distances, stirring blades fixed to the sleeves in a circumferential array, and further comprising a monitoring case, the monitoring case being rotatably connected to the rotating shaft, the monitoring case being located between the stirring case and the sleeves distributed at equidistant distances, the monitoring case having monitoring blades fixed to it in a circumferential array, and the monitoring case being provided with a monitoring speed adjustment mechanism for monitoring the viscosity of the solution and adjusting the rotation speed of the rotating shaft.

[0007] Furthermore, particularly preferably, the monitoring speed adjustment mechanism includes a pressing case, the pressing case is fixed inside the monitoring case, an arc-shaped rod is fixed to the pressing case, the arc-shaped rod is located inside the monitoring case, a fixing plate is fixed to the rotating shaft, the fixing plate slides against the arc-shaped rod, a spring is provided between the fixing plate and the pressing case, a first piston rod slides against the rotating shaft, an arc-shaped chute is provided inside the pressing case, and the arc-shaped chute of the pressing case is press-fitted onto the first piston rod.

[0008] Furthermore, particularly preferably, the rack is fixed to a motor via a mounting frame, a first drive wheel is fixed to the output shaft of the motor, a second drive wheel is spline-connected to the rotating shaft, the second drive wheel is located outside the stirring case, and the first drive wheel is drive-fitted to the second drive wheel.

[0009] Furthermore, particularly preferably, a first fixed case is fixed within the rotating shaft, the first fixed case is in sliding contact with the first piston rod, an intermediate case is fixed within the rotating shaft, a sealing plate is rotatably connected to one side of the intermediate case away from the cover, the intermediate case and the sealing plate on it are combined as a chamber, the chamber formed by the combination of the intermediate case and the sealing plate on it and the first fixed case are in communication via a duct, a second fixed case is fixed within the stirring case away from the cover, a second piston rod is in sliding contact with the second fixed case, the second fixed case and the chamber formed by the combination of the intermediate case and the sealing plate on it are in communication via a duct, a rotating frame is fixed to the second piston rod, and the rotating frame is rotatably connected to the second drive wheel.

[0010] Furthermore, particularly preferably, the device includes a position adjustment mechanism for adjusting the positions of the sleeves, which are distributed at equal distances from each other, the position adjustment mechanism being provided on the cover, the position adjustment mechanism including a sliding rod, the sliding rod sliding against the cover, a rotating case being fixed to the sliding rod, a first fixed frame being rotatably connected to the rotating case, the sleeves closest to the cover being fixed to the first fixed frame, the sleeves distributed at equal distances from each other all being spline-connected to the rotating shaft, and a scissor-link type telescopic frame being provided between the sleeves distributed at equal distances from each other and the rotating shaft.

[0011] Furthermore, particularly preferably, a second fixing frame is fixed to one side of the cover away from the rack, a second sliding plate is slidably in contact with the second fixing frame, a bidirectional screw is rotatably connected between the cover and the second fixing frame, the bidirectional screw is fixed to one side of the rotating shaft closer to the cover, and the second sliding plate is screwed onto the bidirectional screw.

[0012] Furthermore, particularly preferably, a third fixed case is fixed to the second fixed frame, a third piston rod is slidably in contact with the third fixed case, the third piston rod is fixed to the second sliding plate, a fourth piston rod is fixed to one side of the sliding rod away from the rotating case, a fourth fixed case is slidably in contact with the fourth piston rod, and the third fixed case and the fourth fixed case are in communication via a duct.

[0013] Furthermore, more preferably, a screw rod is rotatably connected to the cover, the screw rod is connected to an external power source, a first sliding plate is screwed onto the screw rod, and the first sliding plate is fixed to the fourth fixed case.

[0014] Furthermore, particularly preferably, a material injection pipe is slidably in contact with the cover, the material injection pipe is in communication with the rotating case, a rotating plate is rotatably connected to one side of the rotating case away from the cover, the rotating case together with the rotating plate forms a chamber, a chamber is provided within the sleeve, the sleeve chamber closest to the rotating case is in communication with the chamber between the rotating case and the rotating plate via a duct, adjacent sleeve chambers are in communication via ducts, the sleeve is in communication with adjacent and circumferentially array-distributed stirring blades, and through holes are provided that are distributed equidistant from the stirring blades.

[0015] Compared to conventional technologies, the present invention has the following advantages. The present invention uses mannitol as an excipient to prepare mitomycin and mitomycin freeze-dried powder, and compared to other technologies, it has advantages such as improved stability, improved solubility, easier storage, and improved quality and cost-effectiveness, which helps to ensure the quality and stability of mitomycin freeze-dried powder and improves its practicality in clinical applications, the viscosity of the mixed solution in the stirring case is monitored by fitting monitoring blades distributed equidistant from the monitoring case, and the rotation speed of the stirring blades is adjusted synchronously based on the viscosity of the mixed solution, preventing excessive heat generation of the mixed solution due to the rotation speed of the stirring blades being too fast, guaranteeing the quality of the finished product and improving the preparation efficiency of the finished product, and the stirring blades are distributed equidistant and uniformly. The roots uniformly disperse the mannitol powder (or mitomycin solution) inside the stirring case, improving the mixing efficiency between the mannitol powder (or mitomycin solution) and the mixed solution. The second sliding plate engages with a bidirectional screw, adjusting the vertical position of the stirring blades, which are distributed equidistant and circumferentially in an array based on the number of rotations of the rotating shaft. This prevents stepwise temperature changes due to rotation at a single position of the stirring blades and further reinforces the uniformity of material supply. The screw rod drives the engagement of the first sliding plate, synchronizing the arrangement of the stirring blades based on the total amount of mixed solution in the stirring case, thereby ensuring that the equidistant and circumferentially distributed stirring blades provide a mixing effect on the mixed solution in the stirring case. [Brief explanation of the drawing]

[0016] [Figure 1] This is a schematic diagram of the three-dimensional structure of the present invention. [Figure 2] This is a schematic diagram of the three-dimensional internal structure of the stirring case of the present invention. [Figure 3] This is a schematic diagram of the three-dimensional structure of the fitting relationship between the rotating shaft and the monitoring case of the present invention. [Figure 4] This is a cross-sectional view of the three-dimensional structure of the monitoring speed adjustment mechanism of the present invention. [Figure 5] This is a three-dimensional cross-sectional view of the fitting relationship between the pressing case and the first piston rod of the present invention. [Figure 6] It is a three-dimensional structural sectional view of the fitting relationship between the rotating case and the first fixed frame of the present invention. [Figure 7] It is a three-dimensional structural sectional view of the position adjustment mechanism of the present invention. [Figure 8] It is a three-dimensional structural sectional view of the communication relationship between the rotating case and the material injection pipe of the present invention. [Figure 9] It is a three-dimensional structural sectional view of the communication relationship between the sleeve and the stirring blade of the present invention. [Figure 10] It is a schematic three-dimensional structural view of the stirring blade of the present invention.

Embodiments for Carrying Out the Invention

[0017] In order to further clarify the object, technical solution and advantages of the present invention, the present invention will be described in more detail below with reference to the drawings while referring to specific embodiments. It should be understood that these descriptions are illustrative and do not limit the scope of the present invention. Also, in the following description, in order to avoid unnecessarily confusing the concept of the present invention, the description of well-known structures and technologies is omitted.

[0018] As shown by research, when preparing a conventional mitomycin solution, it is usually necessary to add an excipient to improve the stability of mitomycin. Due to the characteristics of the excipient, the prepared lyophilized powder has poor solubility, insufficient stability, poor performance in the lyophilization process, high cost, and complex quality control. There may be disadvantages such as these.

Examples

[0019] Mitomycin lyophilized powder, prepared in the following parts, Mitomycin: 1.5 - 5 mg / ml, Mannitol powder: 15 - 100 mg / ml, L-serine: 1.7 - 6 mg / ml, tert-butyl alcohol: 0.2 - 0.5 ml / ml, Potassium dihydrogen phosphate: 3.7 - 9 mg / ml, Potassium hydroxide: Prepare to pH 8-9, Water for injection: Replenish to volume, The production steps for mitomycin freeze-dried powder are specifically as follows: In Step 1, the raw materials are sieved through a 200-mesh sieve to prepare them for use. In step 2, approximately 60% of the prescribed amount of sterile water for injection is weighed into a liquid mixing tank, and the sterile water for injection is cooled to a temperature of 1-5°C. In step 3, add the prescribed amount of mannitol powder to the liquid mixing tank. In step 4, the prescribed amount of mitomycin is dispersed in an appropriate amount of sterile water for injection (1-5°C) in an isolator, then added to the liquid mixing tank, and the liquid mixing tank is started and stirred until completely dissolved. In step 5, replenish the entire volume with sterile water for injection (1-5°C), maintain the temperature of the drug solution at 1-5°C, and continue stirring. Step 6 is characterized by controlling the temperature of the liquid mixing tank to -2 to 2°C (tolerance range -2 to 5°C), filtering it online, and filling it.

[0020] Using mannitol as an excipient to prepare mitomycin and mitomycin lyophilized powder offers advantages such as improved stability, enhanced solubility, easier storage, and improved quality and cost-effectiveness compared to other techniques. This helps ensure the quality and stability of mitomycin lyophilized powder and further enhances its practicality in clinical applications.

[0021] As research has shown, in conventional techniques, the temperature inside the mixing vessel must be constantly monitored during the preparation of mitomycin solution. If the temperature inside the mixing vessel is too high, it destroys the molecular structure of mitomycin, causing it to become ineffective and further affecting the quality of the finished product (mitomycin solution). Furthermore, during the mixing process, heat is generated when the blades and the mixed solution come into contact and rub against each other. If the viscosity of the mixed solution inside the mixing vessel gradually increases and the rotation speed of the blades is fast, the amount of heat generated by the blades and the mixed solution gradually increases, causing the temperature inside the mixing vessel to become too high and further affecting the quality of the finished product. If the rotation speed of the blades is slow, the mixing time for mitomycin is extended, reducing the efficiency of preparing the mitomycin solution. [Examples]

[0022] Based on Example 1, the equipment for preparing mitomycin freeze-dried powder includes a rack 1, as shown in Figures 1-3, with a stirring case 2 for preparing the mitomycin solution fixed to the rack 1, a discharge pipe for discharging the prepared mitomycin solution provided on the lower side of the stirring case 2, a cover 3 fixed to the upper side of the stirring case 2, a water supply pipe and an exhaust pipe for communicating with an external vacuum pump provided on the upper side of the cover 3, and the exhaust pipe and water supply pipe exhibit a mirror image distribution, and both the stirring case 2 and the cover 3 are rotatably connected by a rotating shaft 4, with the portion of the rotating shaft 4 located inside the stirring case 2 and the stirring case 2 Splines are provided on the lower part of each component, and sleeves 5 are provided on the spline portion located inside the stirring case 2 of the rotating shaft 4, with sleeves 5 distributed at equal vertical distances. Stirring blades 6 are fixed to the outside of the sleeves 5, with a circumferential array distribution. A monitoring case 7 for monitoring the viscosity of the solution is rotatably connected to the rotating shaft 4, and the monitoring case 7 is located between the stirring case 2 and the sleeves 5 distributed at equal distances. Monitoring blades 8 are fixed to the outside of the monitoring case 7, with a circumferential array distribution. A monitoring speed adjustment mechanism 9 is provided on the monitoring case 7 for monitoring the viscosity of the solution and adjusting the rotation speed of the rotating shaft 4.

[0023] As shown in Figures 2 to 5, the monitoring speed adjustment mechanism 9 includes a pressing case 901, which is fixed to the inside of the monitoring case 7, and an arc-shaped rod 902 located inside the monitoring case 7 is fixed to the pressing case 901, and a fixing plate 903 that slides against the arc-shaped rod 902 is fixed to the rotating shaft 4, and a spring is provided between the fixing plate 903 and the pressing case 901, and the spring between the two is wound around the outer circumference of the arc-shaped rod 902, and a first piston rod 904 slides against the rotating shaft 4, and the first piston rod 904 and the fixing plate 903 are facing each other. The components are distributed, and an arc-shaped chute is provided inside the pressing case 901 that press-fits with the first piston rod 904. The rack 1 has a motor 905 fixed to it via a mounting frame, and a first drive wheel 906 is fixed to the output shaft of the motor 905. The first drive wheel 906 is a frustoconical friction wheel, and its diameter gradually increases from top to bottom. A second drive wheel 907 is spline-connected to the spline portion on the lower side of the rotating shaft 4. The second drive wheel 907 is a disc-shaped friction wheel, and the second drive wheel 907 is located on the outside of the stirring case 2. The first drive wheel 906 and the second drive wheel 907 are driven-fitted by a pressing friction method, and a first fixed case 908 is fixed to the inside of the rotating shaft 4 and is in sealed sliding contact with the first piston rod 904, and hydraulic fluid is injected into the first fixed case 908, and a relay case 909 is fixed to the inside of the lower side of the rotating shaft 4, and a sealing plate is rotatably connected to the lower side of the relay case 909, and the relay case 909 and the sealing plate on top of it are combined into a chamber, and hydraulic fluid is injected into the chamber in which the relay case 909 and the sealing plate on top of it are combined, and the relay case 909 and A duct connects the chamber, to which the upper sealing plate is assembled, to the first fixed case 908. A second fixed case 910 is fixed to the lower side of the stirring case 2, hydraulic fluid is injected into the second fixed case 910, and a second piston rod 911 is sealed and slidingly contacted to the second fixed case 910. A duct connects the chamber, to which the second fixed case 910 and the sealing plate above it are assembled, to the intermediate case 909. A rotating frame 912, which is rotatably connected to the upper side of the second drive wheel 907, is fixed to the second piston rod 911.

[0024] When it is necessary to prepare a mitomycin solution using this device, the user first siftes the raw materials (mannitol powder, mitomycin powder, etc.) through a 200-mesh sieve, then injects 60% sterile water into the stirring case 2 through the water injection pipe in cover 3, and then insulates the stirring case 2 and the mixed solution inside it with external insulation equipment to prevent external temperature from affecting the production process. At this point, the preparation step is complete.

[0025] After the preparation steps are complete, the user gradually introduces mannitol powder into the stirring case 2 through the water injection pipe in cover 3, extracts gas into the stirring case 2 using an external vacuum pump to maintain a stable pressure environment inside the stirring case 2, and simultaneously starts the motor 905, the output shaft of the motor 905 drives the rotation of the first drive wheel 906, the first drive wheel 906 drives the rotation of the second drive wheel 907 by friction, the second drive wheel 907 drives the rotation of the rotating shaft 4, The rotating shaft 4 drives the joint rotation of the sleeves 5 and the stirring blades 6 on them, which are distributed at equal distances from each other, thereby kneading the water for injection and the mannitol powder. In this process, the rotating shaft 4 drives the stationary plate 903 to rotate, and the stationary plate 903 presses a spring between it and the pressing case 901. The stationary plate 903 drives the pressing case 901 and the monitoring blades 8, which are distributed at equal distances from the monitoring case 7, via the spring until the spring force between the two is greater than the rotational resistance of the monitoring blades 8 which are distributed at equal distances from the monitoring case 7. As the rotating shaft 4 and the pressing case 901 rotate relative to each other, the arc-shaped chute inside the pressing case 901 presses and drives the first piston rod 904 to move toward the fixing plate 903, thereby pushing the hydraulic fluid in the first fixing case 908 into the relay case 909 via the duct, the hydraulic fluid in the relay case 909 flows into the second fixing case 910 via the duct, and the second piston rod 911 moves the hydraulic fluid Pressed upward, the second piston rod 911 drives the rotating frame 912 upward, which drives the second transmission wheel 907 upward, thereby reducing the transmission ratio between the first transmission wheel 906 and the second transmission wheel 907. If the spring force between the two is greater than the rotational resistance of the monitoring vanes 8 distributed equidistant from the monitoring case 7, the second transmission wheel 907 is positioned in the center of the first transmission wheel 906, and the fixing plate 903 is positioned in the center of the arc-shaped rod 902.

[0026] As the amount of mannitol powder added gradually increases, the viscosity of the mixed solution in the stirring case 2 gradually increases. Both the rotational speed of the equidistant monitoring blades 8 and the viscosity of the mixed solution affect the heat generated during the stirring process of the mixed solution. The rotational resistance of the monitoring blades 8, which are equidistant from the monitoring case 7, increases synchronously as the viscosity of the mixed solution increases. As a result, the monitoring blades 8, which are equidistant from the monitoring case 7, gradually rotate again relative to the rotation axis 4. The first piston rod 904 moves again towards the fixed plate 903, and the oil circuit drives the second piston rod 911 upwards again, thereby slowing down the stirring speed of the apparatus. To prevent excessive heating of the mixed solution due to the rotation of the stirring blades 6 being too fast, which would affect the quality of the product, the user repeats the above steps to dissolve and knead the mannitol powder until all of the mannitol powder has been added. The user controls the external supply device to stop the gas supply into the stirring case 2, and the monitoring blades 8, which are distributed equidistant from the monitoring case 7, engage to monitor the viscosity of the mixed solution in the stirring case 2. Furthermore, the rotation speed of the stirring blades 6 is adjusted synchronously based on the viscosity of the mixed solution, preventing excessive heat generation of the mixed solution due to the rotation speed of the stirring blades 6 being too fast, thereby ensuring the quality of the finished product and improving the efficiency of the finished product preparation.

[0027] After the addition and mixing of mannitol powder is complete, the user pre-mixes the mitomycin powder with a specified amount of water for injection (a high-concentration mitomycin solution with a viscosity higher than that of the mixed solution), and then gradually injects the pre-mixed solution into the stirring case 2 through the water inlet pipe in cover 3. At the same time, the user continues to control the device to mix and stir the mixed solution in stirring case 2, and in this process, the rotation speed of the rotating shaft 4, the equidistant sleeves 5 and the stirring blades 6 on them are inversely proportional to the viscosity of the mixed solution, thereby ensuring that the stirring blades 6 and the mixed solution do not generate excessive heat. The user repeats the above steps and continues to mix the mitomycin powder and the mixed solution until the mixing of the mitomycin powder in the mixed solution is complete.

[0028] After the mitomycin powder has been kneaded in the mixed solution, the user fills the stirring case 2 with water for injection through the water inlet pipe in cover 3. This reduces the viscosity of the mixed solution, increasing the rotation speed of the rotating shaft 4, the equidistant sleeves 5, and the stirring blades 6 above them, ensuring that the mixed solution is kneaded more quickly and preventing excessive heat generation due to friction between the mixed solution and the stirring blades 6. The user continues to control the rotation of the rotating shaft 4 and knead the mixed solution in the stirring case 2 with the equidistant sleeves 5 and the stirring blades 6 above them until all of the mixed solution has been kneaded. The user then closes the motor 905, discharges the prepared mixed solution through the discharge pipe on the bottom of the stirring case 2, and proceeds with subsequent filtration, filling, and freeze-drying powder preparation. The user then repeats the above preparation process until all of the mitomycin solution has been prepared, at which point the use of the device is complete. [Examples]

[0029] Based on Embodiment 2, as shown in Figures 1, 2 and 6-8, the system further includes a position adjustment mechanism 10 for adjusting the positions of the equidistant sleeves 5, the position adjustment mechanism 10 is provided on the cover 3, the position adjustment mechanism 10 includes a sliding rod 1001, the sliding rod 1001 slides against the cover 3, a rotating case 1002 is fixed to the lower side of the sliding rod 1001, a first fixed frame 1003 fixed to the uppermost sleeve 5 is rotatably connected to the inner circumference of the rotating case 1002, all equidistant sleeves 5 are spline connected to the rotating shaft 4, a scissor link type telescopic frame 1004 is provided between the equidistant sleeves 5 and the rotating shaft 4, a screw rod 1005 connected to an external power source is rotatably connected to the upper side of the cover 3, a first sliding plate 1006 is screwed onto the screw rod 1005, a second fixed frame 1007 is fixed to the upper side of the cover 3, and the second fixed frame 10 The second sliding plate 1008 is in sliding contact with 07, a bidirectional screw 1009 fixed to the upper side of the rotating shaft 4 is rotatably connected between the cover 3 and the second fixed frame 1007, the second sliding plate 1008 is screwed onto the bidirectional screw 1009, the third fixed case 1010 is fixed to the second fixed frame 1007, hydraulic fluid is injected into the third fixed case 1010, and the third piston rod 1 fixed to the second sliding plate 1008 is attached to the third fixed case 1010. 011 is sealed and slidingly contacted, the fourth fixed case 1012 is fixed to the first sliding plate 1006, hydraulic fluid is injected into the fourth fixed case 1012, the third fixed case 1010 and the fourth fixed case 1012 are in communication via a duct, and the duct between the two is a flexible duct, the fourth piston rod 1013 is sealed and slidingly contacted to the fourth fixed case 1012, and the fourth piston rod 1013 is fixed to the upper side of the sliding rod 1001.

[0030] As shown in Figures 8 to 10, a material injection pipe 11 communicating with a rotating case 1002 is slidably in contact with the cover 3, a rotating plate 12 is rotatably connected to the lower side of the rotating case 1002, the rotating case 1002 together with the rotating plate 12 form a chamber, a chamber is provided within the sleeve 5, the uppermost sleeve 5 chamber communicates with the chamber between the rotating plates 12 via a duct and the rotating case 1002, adjacent sleeve 5 chambers communicate with each other via a duct, and the duct between adjacent sleeve 5 chambers is an elastic duct, the sleeve 5 communicates with adjacent and circumferentially arrayed stirring blades 6, through holes distributed at equal distances in the stirring blades 6 are provided, the area of ​​the through holes distributed at equal distances in the stirring blades 6 gradually increases from approaching adjacent sleeves 5 to moving away from adjacent sleeves 5, used to improve the uniformity of material supply, and the orientation of the through holes in the stirring blades 6 is opposite to the rotation direction of the stirring blades 6.

[0031] When the user injects mannitol powder into the stirring case 2, the user first connects the external supply device to the material injection pipe 11, and then the user continues to gradually inject the mannitol powder into the rotating case 1002 using air via the external supply device. After the mannitol powder is injected into the rotating case 1002, it flows into the uppermost sleeve 5 chamber via the rotating plate 12 and duct. Some of the mannitol powder that enters the sleeve 5 chamber is blown by air into the uppermost four stirring blades 6, and then flows and is uniformly dispersed to the outside through through holes distributed at equal distances from the stirring blades 6, and is then kneaded, and the uppermost sleeve 5 chamber Some of the mannitol powder flows into the lower sleeve 5 chamber via the lower duct, and all of the lower sleeve 5 chambers and the stirring blades 6 above them are similar, so that the mannitol powder is uniformly dispersed in the mixed solution by the stirring blades 6 which are distributed equidistant and circumferentially, thereby improving the mixing efficiency of the mannitol powder and the mixed solution. Meanwhile, the method of injecting the mitomycin solution is the same as above, so that the mannitol powder (or mitomycin solution) is uniformly dispersed inside the stirring case 2 by the stirring blades 6 which are distributed equidistant and uniformly, thereby improving the mixing efficiency of the mannitol powder (mitomycin solution) and the mixed solution.

[0032] In the above mixing process, the rotating shaft 4 rotates by driving the bidirectional screw 1009, the bidirectional screw 1009 drives the second sliding plate 1008 upward via the screw threads, the second sliding plate 1008 drives the third piston rod 1011 upward, the hydraulic fluid in the third fixed case 1010 is pressed and flows through the duct into the fourth fixed case 1012, the hydraulic fluid is pressed and drives the fourth piston rod 1013 downward, the fourth piston rod 1013 drives the sliding rod 1001 downward, the sliding rod 1001 moves downward by the rotating case 1002 driving the first fixed frame 1003. The first fixed frame 1003 drives the uppermost sleeve 5 and the stirring blade 6 above it to move both downwards, and the uppermost sleeve 5 drives all the lower sleeves 5 by the scissor-link telescopic frame 1004 to move them equidistant downwards. In this process, all the stirring blades 6 are positioned below the liquid surface of the mixed solution and are engaged with the bidirectional screw 1009 by the second sliding plate 1008. The vertical position of the stirring blades 6, which are distributed equidistant and circumferentially in an array based on the number of rotations of the rotating shaft 4, is adjusted to prevent the temperature from changing in steps due to the rotation of a single position of the stirring blades 6 and to further reinforce the uniformity of the material supply.

[0033] When injecting water for injection into the stirring case 2 twice, the user controls the rotation of the screw rod 1005 with an external power source. The screw rod 1005 drives the first sliding plate 1006 upward, which is driven upward by the fourth fixed case 1012 and the fourth piston rod 1013, which drives the sliding rod 1001 upward, which drives the rotating case 1002, the first fixed frame 1003 and the uppermost sleeve 5 upward in a synchronous manner, until the uppermost sleeve 5 and the stirring blade 6 above it are pushed upward to their limit. Until it moves to its position, the uppermost sleeve 5 is driven upward synchronously by the scissor-link type telescopic frame 1004, which drives all the lower sleeves 5 upward synchronously and equidistantly. At this time, the stirring blades 6, which are distributed equidistantly and circumferentially in an array, are uniformly distributed within the stirring case 2. The screw rod 1005 drives the first sliding plate 1006 to engage, and the arrangement of the stirring blades 6 is synchronously adjusted based on the total volume of the mixed solution in the stirring case 2, thereby ensuring the kneading effect of the stirring blades 6, which are distributed equidistantly and circumferentially in an array, on the mixed solution in the stirring case 2.

[0034] The above embodiments are for illustrating the technical solutions of the present invention and do not limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, as those skilled in the art will understand, the technical solutions of the present invention can be modified or replaced with equivalents without departing from the substance and scope of the technical solutions of the present invention. [Explanation of symbols]

[0035] 1 rack 2. Mixing case 3 Cover 4 rotation axes 5 sleeves 6. Stirring blades 7. Surveillance Cases 8. Surveillance vanes 9 Monitoring speed adjustment mechanism 901 Press Case 902 Arc-shaped rod 903 Fixed plate 904 First piston rod 905 Motor 906 First drive wheel 907 Second drive wheel 908 First fixed case 909 Relay Case 910 Second fixed case 911 Second piston rod 912 Rotation Frame 10 Position adjustment mechanism 1001 Sliding rod 1002 Rotating Case 1003 First fixed frame 1004 Scissors-link type telescopic frame 1005 Screw Rod 1006 First sliding plate 1007 Second fixed frame 1008 Second sliding plate 1009 Two-way screw 1010 Third fixed case 1011 Third piston rod 1012 Fourth fixed case 1013 Fourth piston rod 11 Material injection pipe 12 Rotating Plates

Claims

1. The following quantities will be prepared: Mitomycin: 1.5-5 mg / ml Mannitol powder: 15-100 mg / ml L-serine: 1.7-6 mg / ml tert-butyl alcohol: 0.2-0.5 ml / ml, Potassium dihydrogen phosphate: 3.7–9 mg / ml Potassium hydroxide: Prepare to pH 8-9, Water for injection: Replenish to volume, The production steps for the mitomycin freeze-dried powder are specifically as follows: In step 1, the raw materials are sieved through a 200-mesh sieve to prepare them for use. In step 2, approximately 60% of the prescribed amount of sterile water for injection is weighed into a liquid mixing tank, and the sterile water for injection is cooled to a temperature of 1-5°C. In step 3, add the prescribed amount of mannitol powder to the liquid mixing tank. In step 4, the prescribed amount of mitomycin is dispersed in an isolator with an appropriate amount of sterile water for injection (1-5°C), then added to the liquid mixing tank, and the liquid mixing tank is started and stirred until completely dissolved. In step 5, replenish the entire volume with sterile water for injection (1-5°C), maintain the temperature of the drug solution at 1-5°C, and continue stirring. The mitomycin freeze-dried powder is characterized in that, in step 6, the temperature of the liquid compounding tank is controlled to -2 to 2°C (tolerance range -2 to 5°C), and the liquid is filtered online and filled.

2. The stirring case (2) is fixed to a rack (1), a cover (3) is fixed to one side of the stirring case (2) away from the rack (1), the cover (3) is provided with a water supply pipe and an exhaust pipe for communication with an external vacuum pump, a discharge pipe is provided to one side of the stirring case (2) away from the cover (3), the stirring case (2) and the cover (3) are both rotatably connected to a rotating shaft (4), sleeves (5) are provided on the rotating shaft (4) at equal distances from each other, and stirring blades (6) are fixed to the sleeves (5) in a circumferential array distribution. A mitomycin freeze-dried powder preparation apparatus, further comprising a monitoring case (7), wherein the monitoring case (7) is rotatably connected to the rotating shaft (4), the monitoring case (7) is located between the stirring case (2) and the sleeve (5) which are distributed equidistant from each other, monitoring blades (8) which are circumferentially arrayed and fixed to the monitoring case (7), and the monitoring case (7) is provided with a monitoring speed adjustment mechanism (9) for monitoring the viscosity of the solution and adjusting the rotation speed of the rotating shaft (4).

3. The apparatus for preparing mitomycin freeze-dried powder according to claim 2, characterized in that the monitoring speed adjustment mechanism (9) includes a pressing case (901), the pressing case (901) is fixed inside the monitoring case (7), an arc-shaped rod (902) is fixed to the pressing case (901), the arc-shaped rod (902) is located inside the monitoring case (7), a fixing plate (903) is fixed to the rotating shaft (4), the fixing plate (903) is in sliding contact with the arc-shaped rod (902), a spring is provided between the fixing plate (903) and the pressing case (901), a first piston rod (904) is in sliding contact with the rotating shaft (4), an arc-shaped chute is provided inside the pressing case (901), and the arc-shaped chute of the pressing case (901) is press-fitted onto the first piston rod (904).

4. The apparatus for preparing mitomycin freeze-dried powder according to claim 3, characterized in that the rack (1) has a motor (905) fixed to it via a mounting frame, a first drive wheel (906) fixed to the output shaft of the motor (905), a second drive wheel (907) spline-connected to the rotating shaft (4), the second drive wheel (907) located outside the stirring case (2), and the first drive wheel (906) is drive-fitted to the second drive wheel (907).

5. A first fixed case (908) is fixed inside the rotating shaft (4), the first fixed case (908) is in sliding contact with the first piston rod (904), an intermediate case (909) is fixed inside the rotating shaft (4), a sealing plate is rotatably connected to one side of the intermediate case (909) away from the cover (3), the intermediate case (909) and the sealing plate on it are combined to form a chamber, and the chamber formed by the combination of the intermediate case (909) and the sealing plate on it and the first fixed case (908) are connected via a duct, and the stirring case (2 The apparatus for preparing mitomycin freeze-dried powder according to claim 4, characterized in that a second fixed case (910) is fixed to one side of the cover (3) away from the cover (3) of the ), a second piston rod (911) is slidably contacted with the second fixed case (910), the second fixed case (910) and the chamber formed by combining the relay case (909) and the sealing plate above it are connected via a duct, a rotating frame (912) is fixed to the second piston rod (911), and the rotating frame (912) is rotatably connected to the second drive wheel (907).

6. The apparatus for preparing mitomycin freeze-dried powder according to claim 5, further comprising a position adjustment mechanism (10) for adjusting the positions of the equidistant sleeves (5), the position adjustment mechanism (10) being provided on the cover (3), the position adjustment mechanism (10) including a sliding rod (1001), the sliding rod (1001) sliding in contact with the cover (3), a rotating case (1002) being fixed to the sliding rod (1001), a first fixed frame (1003) being rotatably connected to the rotating case (1002), the sleeves (5) closest to the cover (3) being fixed to the first fixed frame (1003), all equidistant sleeves (5) being spline-connected to the rotating shaft (4), and a scissor-link type telescopic frame (1004) being provided between the equidistant sleeves (5) and the rotating shaft (4).

7. The apparatus for preparing mitomycin freeze-dried powder according to claim 6, characterized in that a second fixing frame (1007) is fixed to one side of the cover (3) away from the rack (1), a second sliding plate (1008) is slidably contacted with the second fixing frame (1007), a bidirectional screw (1009) is rotatably connected between the cover (3) and the second fixing frame (1007), the bidirectional screw (1009) is fixed to one side of the rotating shaft (4) closer to the cover (3), and the second sliding plate (1008) is screwed onto the bidirectional screw (1009).

8. The apparatus for preparing mitomycin freeze-dried powder according to claim 7, characterized in that a third fixed case (1010) is fixed to the second fixed frame (1007), a third piston rod (1011) is slidably contacted to the third fixed case (1010), the third piston rod (1011) is fixed to the second sliding plate (1008), a fourth piston rod (1013) is fixed to one side of the sliding rod (1001) away from the rotating case (1002), a fourth fixed case (1012) is slidably contacted to the fourth piston rod (1013), and the third fixed case (1010) and the fourth fixed case (1012) are in communication via a duct.

9. The apparatus for preparing mitomycin freeze-dried powder according to claim 8, characterized in that a screw rod (1005) is rotatably connected to the cover (3), the screw rod (1005) is connected to an external power source, a first sliding plate (1006) is screwed onto the screw rod (1005), and the first sliding plate (1006) is fixed to the fourth fixing case (1012).

10. The apparatus for preparing mitomycin freeze-dried powder according to claim 9, characterized in that a material injection pipe (11) is slidably in contact with the cover (3), the material injection pipe (11) is in communication with the rotating case (1002), a rotating plate (12) is rotatably connected to one side of the rotating case (1002) away from the cover (3), the rotating case (1002) together with the rotating plate (12) forms a chamber, a chamber is provided in the sleeve (5), the sleeve (5) chamber closest to the rotating case (1002) is in communication with the chamber between the rotating case (1002) and the rotating plate (12) via a duct, adjacent sleeve (5) chambers are in communication via ducts, the sleeve (5) is in communication with adjacent and circumferentially array-distributed stirring blades (6), and the stirring blades (6) are provided with through holes distributed at equal distances from each other.

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