Device and method for stirring and neutralizing melphalan hydrochloride preparation for injection

Abstract

The invention discloses a device and a method for stirring and neutralizing a melphalan hydrochloride preparation for injection, and relates to the technical field of stirring and neutralizing devices. Comprising a ventilation system, a control system and a barrel, a feeding pipe is connected to the upper side of the barrel, a discharging pipe is connected to the lower side of the barrel, a coil is arranged in the barrel, a driving motor is installed on the barrel, a transmission shaft is installed on an output shaft of the driving motor, and a cam and a lifting plate are sequentially installed on the upper side of the transmission shaft; a telescopic plate A and a telescopic plate B are connected between the lifting plate and the transverse plate; a through groove is formed in the middle of the transmission shaft, a cross rod is rotationally mounted in the through groove, a gear is arranged in the middle of the cross rod, and a mixing plate is mounted on the cross rod; a rack is slidably mounted on the inner wall of the transmission shaft; a filter is mounted below the transmission shaft; the circulating chamber drives a refrigerant to circularly flow and cools the mixing plate and the cross rod, the mixing plate and the coil are matched for stirring and temperature control, and the filter membrane is used for filtering the mixed preparation.

Description

Technical Field

[0001] The invention relates to the technical field of stirring and neutralizing devices, in particular to a stirring and neutralizing device and method for a melphalan hydrochloride preparation for injection. Background Art

[0002] Melphalan hydrochloride for injection is a chemotherapy drug. It is mainly used to treat certain types of cancer, such as multiple myeloma. Melphalan achieves its therapeutic purpose by interfering with the DNA synthesis and repair mechanism of cancer cells, inhibiting the growth and division of cancer cells.

[0003] The role of stirring in the preparation production process is mainly to ensure that the drug ingredients are evenly mixed during the drug preparation process and to improve the stability and consistency of the drug. When preparing lyophilized powder preparations of melphalan hydrochloride for injection, stirring helps melphalan hydrochloride to fully dissolve in the mixed solvent and avoid aggregation of drug particles, thereby ensuring the quality and efficacy of each batch of drugs. In addition, stirring can also promote heat exchange between the solvent and the drug, help control the temperature during the preparation process, and further ensure the quality of the drug. The existing preparation stirring and neutralization devices mainly have the following problems: (1) The single stirring method makes it impossible to quickly dissolve and neutralize the preparation raw materials, and (2) During the mixing process, the dissolution effect of the melphalan hydrochloride preparation raw materials is poor, resulting in a slow neutralization efficiency and unable to meet the use requirements. Summary of the invention

[0004] The object of the present invention is to provide a stirring and neutralizing device and method for a melphalan hydrochloride preparation for injection, so as to solve the problems raised in the prior art.

[0005] To achieve the above-mentioned purpose, the present invention provides the following technical solutions: a stirring and neutralizing device for melphalan hydrochloride preparation for injection, including a ventilation system and a control system, including a cylinder, a sleeve is arranged in the cylinder, a horizontal plate is arranged on the upper side of the sleeve, a partition is arranged on the lower side of the sleeve, a plurality of groups of vertical plates are arranged on the outer side of the sleeve, and a plurality of groups of annular grooves are arranged in sequence on the inner side of the sleeve; a feed pipe is connected to the upper side of the cylinder, the feed pipe is connected to the pressurizing system, a discharge pipe is connected to the lower side of the cylinder, a coil is arranged inside the cylinder, a motor seat is installed on the cylinder, a drive motor is vertically installed on the motor seat, a transmission shaft is installed in the sleeve, the upper end of the transmission shaft passes through the horizontal plate and is connected to the output end of the drive motor, and the lower end of the transmission shaft is connected to the output end of the drive motor. It passes through the partition and is rotatably installed on the bottom of the cylinder through the bearing; the transmission shaft is hollow inside, and a cam and a lifting plate are successively installed on the upper side of the transmission shaft, the cam and the lifting plate are located above the horizontal plate, and telescopic plates A and B are installed between the lifting plate and the horizontal plate; in the horizontal direction, a plurality of groups of through grooves are arranged in the middle part of the transmission shaft, a cross bar is rotatably installed in the through groove, a gear is arranged in the middle part of the cross bar, and rotating parts are rotatably arranged at both ends of the cross bar, the rotating parts at both ends are inserted into the annular grooves, the annular grooves restrict the rotating parts, so that the rotating parts slide in the annular grooves and cannot rotate with the cross bar, and two groups of mixing plates are installed on the cross bar, and the mixing plates and the coil cooperate to perform stirring and temperature control.

[0006] In the vertical direction, a sliding groove is provided on the inner wall of the transmission shaft, a rack is slidably installed in the sliding groove, and the gear and the rack are meshed; a filter is installed on the lower side of the transmission shaft; the mixing plate and the coil cooperate to stir and control the temperature, and the filter membrane on the filter filters the mixed preparation; the cam is located above the lifting plate, and a plurality of protrusions are provided on the opposite side of the cam and the lifting plate. The cam is installed on the transmission shaft, and the lifting plate slides on the inner wall of the cylinder, and the inner wall of the cylinder limits the lifting plate so that the lifting plate can only move up and down. A displacement sensor is installed on the lifting plate, and the displacement sensor is used to monitor the distance between the lifting plate and the cam. A guide shaft is slidably installed on the lifting plate, and the lower end of the guide shaft is installed on the horizontal plate. A first spring is connected between the lifting plate and the horizontal plate, and the first spring is sleeved on the guide shaft. The first spring is electrically connected to the control system. The control system controls whether the first spring is energized, adjusts whether the lifting plate contacts the cam, and then controls whether the mixing plate rotates, so as to adjust the mixing effect of the mixing plate.

[0007] The middle part of the lifting plate is sleeved on the transmission shaft, a circular groove is provided in the middle part of the lifting plate, sealing rings are provided between the lifting plate and the transmission shaft on both sides of the circular groove, sliding shafts are provided at both ends of the rack, and a limiting groove is provided on the transmission shaft facing the sliding shaft, and both ends of the sliding shaft pass through the limiting groove and are inserted into the circular groove. When the transmission shaft drives the rack and the sliding shaft to rotate through the sliding groove, the sliding shaft slides in the circular groove, so that the mixing plate can be adjusted to rotate in the process of following the revolution of the transmission shaft.

[0008] The cross bar and the rotating part are hollow inside, and the rotating parts on both sides are provided with circular holes. The circular holes on the rotating parts on both sides are respectively located on opposite sides. Circular plates are installed at both ends of the cross bar, and the circular plates block and seal the annular groove. The circular plates are rotatably installed on the inner wall of the sleeve, and the inner wall of the sleeve supports and limits the circular plates. A cavity is formed between the annular groove and the circular plates, and the cross bar divides the cavity into cavity one and cavity two.

[0009] The cross bar divides the annular groove into cavity one and cavity two, and cavity one and cavity two move with the revolution of the cross bar. The control system obtains the rotation position of the cross bar according to the data of the encoder in the drive motor, and then calculates the positions of cavity one and cavity two. The control system controls the on and off of the solenoid valves in the evaporator tube and the detection tube according to the positions of cavity one and cavity two. That is, when cavity one is connected with the evaporator tube, the solenoid valve in the evaporator tube opens, allowing the refrigerant to enter cavity one through the evaporator tube, and then enter the cross bar from cavity one; when cavity two is connected with the detection tube, the solenoid valve in the detection tube opens, allowing the refrigerant to be transported from the refrigerant in the cross bar to cavity two, and then from cavity two to the detection tube, thereby realizing the entry and outflow of refrigerant during the rotation of the cross bar.

[0010] The telescopic plate A is located outside the telescopic plate B. The telescopic plate A and the telescopic plate B are both composed of an upper cylinder and a lower cylinder, the upper cylinder and the lower cylinder form a sliding sealing connection, the lower cylinders in the telescopic plate A and the telescopic plate B are both installed on the horizontal plate, a diaphragm is connected between the lower cylinders in the telescopic plate A and the telescopic plate B, and the upper cylinders on the telescopic plate A and the telescopic plate B are both installed on the lifting plate;

[0011] A circulation chamber is formed between the lower cylinder, the diaphragm and the transverse plate in the telescopic plate A and the telescopic plate B, and a refrigerant is arranged in the circulation chamber.

[0012] The vertical plate is located between the sleeve and the cylinder, and the vertical plate divides the space between the sleeve and the cylinder into a plurality of sectors, and an evaporation tube and a detection tube are respectively installed in two opposite sectors;

[0013] The evaporation tube and the detection tube are both installed on the sleeve. The inlet of the evaporation tube is connected to a capillary tube through a regulating valve and an expansion valve in sequence. The regulating valve adjusts the flow rate according to the data of the temperature sensor in the capillary tube. Multiple groups of refrigeration plates are installed inside the capillary tube. The multiple groups of refrigeration plates are closely installed on the capillary tube. The capillary tube is connected to the interior of the lower cylinder in the telescopic plate A. The capillary tube is installed on the horizontal plate. The outlet of the evaporation tube passes through the sleeve and is connected to the interior of multiple groups of annular grooves.

[0014] The inlet of the detection tube is connected to the annular groove through the sleeve, and the outlet of the detection tube is connected to the interior of the lower cylinder in the telescopic plate A. The detection tube, capillary tube and evaporation tube are all installed with a one-way valve, a solenoid valve and a temperature sensor in series. The one-way valve in the detection tube, capillary tube and evaporation tube ensures that the refrigerant is transported through the circulation chamber, capillary tube, expansion valve, evaporation tube, cavity 1, the interior of the cross bar, spiral flow channel, cavity 2 and detection tube in sequence. The solenoid valves in the detection tube, capillary tube and evaporation tube are in a closed state when the preparation does not need to be cooled.

[0015] The inner diameter of the capillary tube is smaller than the inner diameter of the evaporation tube, and an air inlet and an air outlet are provided on the cylinder body close to the capillary tube, the air inlet is located on one side of the air outlet, the air inlet is connected to the ventilation system, and the air outlet is connected to the external atmosphere;

[0016] The capillary tubes are distributed in a transverse spiral, and the evaporation tubes and the detection tubes are distributed in a longitudinal spiral.

[0017] A plurality of sets of temperature difference plates A are installed on the inner wall of the evaporating tube, and a plurality of sets of temperature difference plates B are installed on the inner wall of the detecting tube, and the plurality of sets of temperature difference plates A correspond to the plurality of sets of temperature difference plates B one by one. The temperature difference plates A, B and the refrigeration plate are all provided with semiconductors and metal plates of two different materials, and one end of the semiconductors of the two different materials is connected to the metal plate. The two semiconductors on the temperature difference plate A and the two semiconductors on the temperature difference plate B are connected by wires, one of which is connected to the control system, and the two semiconductors on the refrigeration plate are electrically connected to the control system through the wires. The two semiconductors and metal plates on the temperature difference plate A are the cold end of the Seebeck effect, the two semiconductors and metal plates on the temperature difference plate B are the hot end of the Seebeck effect, and the two semiconductors and metal plates on the cooling plate are the cooling end of the Peltier effect. The low-temperature refrigerant enters the interior of the crossbar through the evaporation tube, the annular groove, and the circular hole, and is then transported to the spiral flow channel in the mixing plate through the interior of the crossbar. The temperature of the mixing plate and the crossbar decreases after contacting the refrigerant, and the temperature of the preparation decreases after heat exchange with the mixing plate and the crossbar, so that the mixing plate stirs the preparation while cooling it. The temperature of the refrigerant after heat exchange increases and is transported from the annular groove to the detection tube. The low-temperature refrigerant passes through the evaporation tube and contacts the temperature difference plate A. The temperature of the low-temperature refrigerant increases after heat exchange with the preparation and is transported to the detection tube and contacts the temperature difference plate B. Therefore, the temperature of the hot end is greater than the cold end. The hot end and the cold end generate current through the Seebeck effect and transmit it to the control system. The control system first detects the current and calculates the temperature of the hot end. Finally, the current is used for cooling the cooling end after voltage conversion and rectification.

[0018] The mixing plate is made of spiral twisting, and a plurality of spiral flow channels are arranged inside the mixing plate. The plurality of spiral flow channels are arranged along the spiral of the mixing plate, and the inlets and outlets of the plurality of spiral flow channels are connected to the inside of the cross bar. The outside of the mixing plate is provided with a metal material, and the metal material is in the magnetic field of the coil. When the preparation needs to be heated, the control system connects the coil to the circuit, and a magnetic field is generated at both ends of the coil. The metal material in the mixing plate rotates in the magnetic field of the coil and cuts the magnetic flux lines. Since the metal material rotates while following the revolution of the mixing plate, the movement direction of the metal material changes all the time, eddy currents are generated in the metal material and heat is generated, and the metal material heats the preparation through the mixing plate.

[0019] Another set of temperature sensors and an electronic pH meter are installed in the sleeve. The electronic pH meter monitors the pH of the preparation and feeds back the data to the control system. The temperature sensor on the sleeve monitors the temperature of the preparation raw materials when they are mixed, and feeds back the data to the control system. A switch valve is installed on the partition. The switch valve, another set of temperature sensors and the electronic pH meter are all electrically connected to the control system. The middle part of the filter is rotatably sealed with the transmission shaft. The filter is installed on the sleeve, and a filter membrane is arranged on the filter. A control panel is installed on the cylinder, and the control system is arranged in the control panel. The drive motor has a built-in encoder.

[0020] A stirring and neutralizing method for a melphalan hydrochloride preparation for injection, using a stirring and neutralizing device for a melphalan hydrochloride preparation for injection, and comprising the following stirring and neutralizing method:

[0021] S1. Add a certain amount of water for injection into the sleeve and stir;

[0022] S2. Add sodium sulfobutyl beta-cyclodextrin while stirring, and stir to dissolve;

[0023] S3, cooling the preparation in the sleeve to 2-8°C;

[0024] S4, adding melphalan hydrochloride while stirring, and stirring again to dissolve;

[0025] S5. Add sodium hydroxide solution and hydrochloric acid solution while stirring to adjust the pH value to within the range specified by the process;

[0026] S6. Add water for injection at a temperature not exceeding 25°C while stirring and continue stirring evenly;

[0027] S7. After filtering, the desired preparation is obtained.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] 1. Multiple stirring methods can make the preparation raw materials stirred more evenly. When the protrusion on the cam contacts the protrusion on the lifting plate, the cam pushes the lifting plate to move downward, and the lifting plate drives the sliding shaft to move downward through the circular groove, and the sliding shaft drives the rack to slide downward in the sliding groove, and the rack drives the gear to rotate, and the gear drives the cross bar to rotate, and the cross bar drives the mixing plate to rotate, so that the mixing plate rotates while revolving, and the mixing effect of the mixing plate on the preparation raw materials is improved; when the protrusion on the cam does not contact the protrusion on the lifting plate, the lifting plate drives the sliding shaft to move upward through the circular groove, and the sliding shaft drives the rack to move upward, and the rack drives the gear and the mixing plate to rotate in the opposite direction, and the lifting plate is driven up and down by the cam to reciprocate, so that the mixing plate can continuously rotate forward and reversely, and the mixing effect of the preparation raw materials is further improved.

[0030] 2. The cooling effect of the mixing plate on the preparation raw materials is significantly improved by the refrigerant flowing in the mixing plate. The diaphragm squeezes the refrigerant in the circulation chamber into the capillary tube. Multiple groups of refrigeration plates and ventilation systems cooperate to realize the cooling treatment of the capillary tube, so that the temperature of the refrigerant in the capillary tube is reduced and it is converted from gas to liquid. After the liquid refrigerant passes through the expansion valve, the pressure is released and the temperature drops sharply, and it is converted from liquid to aerosol state. The aerosol state refrigerant enters the evaporation tube after passing through the expansion valve. The refrigerant after passing through the expansion valve is converted from liquid to gas. The gaseous refrigerant passes through the evaporation tube and enters the cavity in the annular groove, and enters the inside of the cross bar from the circular hole on the side of the annular groove and the cross bar. The gaseous refrigerant is diverted from the inside of the cross bar into the spiral flow channel of the mixing plate, and the cooling area is increased through the spiral flow channel. The gaseous refrigerant is heat exchanged with the preparation raw materials through the mixing plate, so that the temperature of the preparation raw materials is quickly reduced when they are mixed.

[0031] 3. Filter the neutralized raw materials through the filter membrane for subsequent processing. After mixing, the raw materials are gradually dissolved and neutralized. The control system opens the switch valve on the partition to allow the dissolved raw materials to be transported downward and pass through the filter membrane on the filter. After being filtered through the filter membrane, they are discharged from the discharge pipe. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 It is a schematic diagram of the overall structure of the present invention;

[0033] Figure 2 yes Figure 1 Forward cross-sectional view (the direction of the arrow indicates the air inlet direction);

[0034] Figure 3 yes Figure 2 A partial enlarged view of the middle A area;

[0035] Figure 4 yes Figure 2 A partial enlarged view of the middle B area;

[0036] Figure 5 yes Figure 2 A partial enlarged view of the middle C area;

[0037] Figure 6 yes Figure 1 Left side cross-sectional view;

[0038] Figure 7 yes Figure 6 Top view after removing the cylinder, etc.;

[0039] Figure 8 yes Figure 7 Stereoscopic diagram (the evaporation tube and the detection tube are only drawn with a single turn);

[0040] Fig. 9 yes Figure 8 Schematic diagram of the structure after removing the cam, etc.;

[0041] Fig.10 yes Fig. 9 Schematic diagram of the structure after removing the lifting plate, etc.;

[0042] Fig.11 yes Fig.10 Schematic diagram of the installation structure without the structure inside the sleeve and the drive motor;

[0043] Fig.12 It is the transport path of the refrigerant in the crossbar (the evaporator tube flows the refrigerant out of the circular hole at one end of the crossbar through cavity one, flows through the inside of the crossbar and the spiral flow channel, and then flows out of the circular hole at the other end of the crossbar to cavity two, and cavity two then transports it to the detection tube);

[0044] Fig.13 It is a three-dimensional diagram of the crossbar (the circular holes are located at opposite ends of the crossbar).

[0045] In the figure: 1, control panel; 11, cylinder; 111, sleeve; 112, horizontal plate; 113, vertical plate; 114, annular groove; 115, partition; 116, switch valve; 12, evaporation tube; 121, temperature difference plate A; 13, detection tube; 131, temperature difference plate B; 14, feed pipe; 15, discharge pipe; 16, coil; 17, capillary tube; 171, refrigeration plate; 18, air inlet; 181, air outlet;

[0046] 2. Driving motor; 21. Transmission shaft; 211. Limiting groove; 212. Sliding groove; 22. Cam; 23. Lifting plate; 231. Guide shaft; 232. First spring; 24. Cross bar; 241. Gear; 242. Rack; 243. Sliding shaft; 244. Round hole; 245. Circular ring plate; 246. Cavity 1; 247. Cavity 2; 248. Rotating part; 25. Filter; 26. Mixing plate; 261. Spiral flow channel; 262. Metal material; 27. Telescopic plate A; 271. Telescopic plate B; 272. Circulation chamber; 273. Diaphragm. DETAILED DESCRIPTION

[0047] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0048] Example: Figure 1-Figure 13As shown, the present invention provides a technical solution of a stirring and neutralizing device and method for a melphalan hydrochloride preparation for injection, a stirring and neutralizing device for a melphalan hydrochloride preparation for injection, comprising a ventilation system, a control system and a barrel 11, a sleeve 111 is sleeved in the barrel 11, a horizontal plate 112 is arranged on the upper side of the sleeve 111, a partition 115 is arranged on the lower side of the sleeve 111, multiple groups of vertical plates 113 are arranged on the outer side of the sleeve 111, and multiple groups of annular grooves 114 are sequentially arranged on the inner side of the sleeve 111; a feed pipe 14 is connected to the upper side of the barrel 11, the feed pipe 14 is connected to the pressurizing system, a discharge pipe 15 is connected to the lower side of the barrel 11, a coil 16 is arranged inside the barrel 11, a motor seat is installed on the barrel 11, a drive motor 2 is vertically installed on the motor seat, a transmission shaft 21 is installed in the sleeve 111, the upper end of the transmission shaft 21 passes through the horizontal plate 112 and is connected to the output end of the drive motor 2, and the lower end of the transmission shaft 21 passes through the partition 115 and is rotatably mounted through a bearing Installed at the bottom of the cylinder 11; the transmission shaft 21 is hollow inside, and a cam 22 and a lifting plate 23 are installed on the upper side of the transmission shaft 21 in sequence. The cam 22 and the lifting plate 23 are located above the horizontal plate 112. A telescopic plate A27 and a telescopic plate B271 are installed between the lifting plate 23 and the horizontal plate 112. The telescopic plate A27 is located outside the telescopic plate B271. The telescopic plates A27 and B271 are both composed of an upper cylinder and a lower cylinder sleeve, and the upper cylinder and the lower cylinder form a sliding Sealed connection, the lower cylinders in the telescopic plate A27 and the telescopic plate B271 are both installed on the horizontal plate 112, a diaphragm 273 is connected between the lower cylinders in the telescopic plate A27 and the telescopic plate B271, and the upper cylinders on the telescopic plate A27 and the telescopic plate B271 are both installed on the lifting plate 23; a circulation chamber 272 is formed between the lower cylinders in the telescopic plate A27 and the telescopic plate B271, the diaphragm 273 and the horizontal plate 112, and a refrigerant is arranged in the circulation chamber 272.

[0049] In the horizontal direction, a plurality of through grooves are provided in the middle of the transmission shaft 21, in which a cross bar 24 is rotatably installed, a gear 241 is provided in the middle of the cross bar 24, and rotating parts 248 are rotatably provided at both ends of the cross bar 24, and the rotating parts 248 at both ends are inserted into the annular groove 114, and the annular groove 114 restricts the rotating part 248 so that the rotating part 248 slides in the annular groove 114 and cannot rotate with the cross bar 24, and two groups of mixing plates 26 are installed on the cross bar 24; in the vertical direction, a sliding groove 212 is provided on the inner wall of the transmission shaft 21, and a rack 242 is slidably installed in the sliding groove 212, and the gear 241 and the rack 242 are meshed; a filter 25 is installed on the lower side of the transmission shaft 21; the mixing plate 26 and the coil 16 cooperate to perform stirring and temperature control, and the filter membrane 25 on the filter filters the mixed preparation.

[0050] The cam 22 is located above the lifting plate 23. A plurality of protrusions are arranged on the opposite side of the cam 22 and the lifting plate 23. The cam 22 is mounted on the transmission shaft 21. The lifting plate 23 slides on the inner wall of the cylinder 11. The inner wall of the cylinder 11 restricts the lifting plate 23 so that the lifting plate 23 can only move up and down. A displacement sensor is mounted on the lifting plate 23. The displacement sensor is used to monitor the distance between the lifting plate 23 and the cam 22. A guide shaft 231 is slidably mounted on the lifting plate 23. The lower end of the guide shaft 231 is mounted on the horizontal plate 112. A first spring 232 is connected between the lifting plate 23 and the horizontal plate 112. The first spring 232 is sleeved on the guide shaft 231. The first spring 232 is electrically connected to the control system. The control system controls whether the first spring 232 is energized, adjusts whether the lifting plate 23 contacts the cam 22, and then controls whether the mixing plate 26 rotates, thereby adjusting the mixing effect of the mixing plate 26.

[0051] The middle part of the lifting plate 23 is hollowly sleeved on the transmission shaft 21, and a circular groove is provided in the middle part of the lifting plate 23. Sealing rings are provided between the lifting plate 23 and the transmission shaft 21 on both sides of the circular groove. Sliding shafts 243 are provided at both ends of the rack 242. A limiting groove 211 is provided on the transmission shaft 21 directly facing the sliding shaft 243. Both ends of the sliding shaft 243 pass through the limiting groove 211 and are inserted into the circular groove. When the transmission shaft 21 drives the rack 242 and the sliding shaft 243 to rotate through the sliding groove 212, the sliding shaft 243 slides in the circular groove, so that the mixing plate 26 can be adjusted to rotate in the process of following the revolution of the transmission shaft 21.

[0052] The cross bar 24 and the rotating part 248 are hollow inside, and the rotating parts 248 on both sides are provided with circular holes 244. The circular holes 244 on the rotating parts 248 on both sides are respectively located on opposite sides. Circular plates 245 are installed at both ends of the cross bar 24. The circular plates 245 block and seal the annular groove 114. The circular plates 245 are rotatably installed on the inner wall of the sleeve 111. The inner wall of the sleeve 111 supports and limits the circular plates 245. A cavity is formed between the annular groove 114 and the circular plates 245. The cross bar 24 divides the cavity into cavity one 246 and cavity two 247.

[0053] The vertical plate 113 is located between the sleeve 111 and the cylinder 11. The vertical plate 113 divides the space between the sleeve 111 and the cylinder 11 into multiple sectors. The evaporation tube 12 and the detection tube 13 are respectively installed in the two opposite sectors; the evaporation tube 12 and the detection tube 13 are both installed on the sleeve 111. The inlet of the evaporation tube 12 is connected to the capillary tube 17 through the regulating valve and the expansion valve in turn. The regulating valve adjusts the flow rate according to the data of the temperature sensor in the capillary tube 17. Multiple groups of refrigeration plates 171 are installed inside the capillary tube 17. The plate 171 is closely mounted on the capillary tube 17, the capillary tube 17 is connected to the interior of the lower cylinder in the telescopic plate A27, the capillary tube 17 is mounted on the horizontal plate 112, the outlet of the evaporation tube 12 passes through the sleeve 111 and is connected to the interior of the multiple groups of annular grooves 114; the inlet of the detection tube 13 passes through the sleeve 111 and is connected to the annular groove 114, the outlet of the detection tube 13 is connected to the interior of the lower cylinder in the telescopic plate A27, and a one-way valve, a solenoid valve and a temperature sensor are installed in series in the detection tube 13, the capillary tube 17 and the evaporation tube 12. The one-way valve in the detection tube 13, the capillary tube 17 and the evaporation tube 12 ensures that the refrigerant is transported through the circulation chamber 272, the capillary tube 17, the expansion valve, the evaporation tube 12, the cavity 1 246, the interior of the cross bar 24, the spiral flow channel 261, the cavity 2 247 and the detection tube 13 in sequence. The solenoid valves in the detection tube 13, the capillary tube 17 and the evaporation tube 12 are in a closed state when the preparation does not need to be cooled. The inner diameter of the capillary tube 17 is smaller than the inner diameter of the evaporation tube 12. An air inlet 18 and an air outlet 181 are provided on the cylinder 11 near the capillary tube 17. The air inlet 18 is located on one side of the air outlet 181. The air inlet 18 is connected to the ventilation system, and the air outlet 181 is connected to the external atmosphere. The capillary tube 17 is distributed in a transverse spiral, and the evaporation tube 12 and the detection tube 13 are distributed in a longitudinal spiral.

[0054] A plurality of sets of temperature difference plates A121 are installed on the inner wall of the evaporating tube 12, and a plurality of sets of temperature difference plates B131 are installed on the inner wall of the detecting tube 13. The plurality of sets of temperature difference plates A121 and the plurality of sets of temperature difference plates B131 correspond to each other one by one. The temperature difference plates A121, B131 and the refrigeration plate 171 are all provided with semiconductors and metal plates of two different materials. One end of the semiconductors of the two different materials are connected to the metal plate. The two semiconductors on the temperature difference plate A121 and the two semiconductors on the temperature difference plate B131 are connected by wires, one of which is connected to the control system. The two semiconductors on the refrigeration plate 171 are electrically connected to the control system through wires.

[0055] The mixing plate 26 is made of spiral twisting, and a plurality of spiral flow channels 261 are arranged inside the mixing plate 26. The plurality of spiral flow channels 261 are arranged along the spiral of the mixing plate 26, and the inlets and outlets of the plurality of spiral flow channels 261 are connected to the inside of the cross bar 24. The outside of the mixing plate 26 is provided with a metal material 262, and the metal material 262 is in the magnetic field of the coil 16; another group of temperature sensors and an electronic pH meter are installed in the sleeve 111, and a switch valve 116 is installed on the partition 115. The switch valve 116, another group of temperature sensors and the electronic pH meter are electrically connected to the control system, the middle part of the filter 25 is rotatably sealed and connected to the transmission shaft 21, the filter 25 is installed on the sleeve 111, and a filter membrane is arranged on the filter 25; a control panel 1 is installed on the cylinder 11, the control system is arranged in the control panel 1, and the drive motor 2 has an encoder built in.

[0056] A stirring and neutralizing method for a melphalan hydrochloride preparation for injection, using a stirring and neutralizing device for a melphalan hydrochloride preparation for injection, and comprising the following stirring and neutralizing method:

[0057] S1, adding a certain amount of water for injection into the sleeve 111 and stirring;

[0058] S2. Add sodium sulfobutyl beta-cyclodextrin while stirring, and stir to dissolve;

[0059] S3, cooling the preparation in the sleeve 111 to 2-8°C;

[0060] S4, adding melphalan hydrochloride while stirring, and stirring again to dissolve;

[0061] S5. Add sodium hydroxide solution and hydrochloric acid solution while stirring to adjust the pH value to within the range specified by the process;

[0062] S6. Add water for injection at a temperature not exceeding 25°C while stirring and continue stirring evenly;

[0063] S7. After filtering, the desired preparation is obtained.

[0064] Working principle: the staff presses the start button on the control panel 1, the device starts, and the control system energizes the first spring 232. Each turn of the first spring 232 gradually shrinks due to the mutual attraction of the magnetic field. The first spring 232 pulls the lifting plate 23 to move downward, so that the protrusion on the lifting plate 23 and the protrusion on the cam 22 do not contact, so the cam 22 cannot push the lifting plate 23 to move.

[0065] The staff puts the required preparation raw materials in sequence through the feed pipe 14, and the control system controls the drive motor 2 to drive the transmission shaft 21 to rotate, and the transmission shaft 21 drives the cross bar 24, the cam 22 and the sliding shaft 243 to revolve. At this time, the cam 22 is in an idling state, and the cross bar 24 drives the mixing plate 26 and the annular plate 245 to revolve. The mixing plate 26 stirs the preparation raw materials in the sleeve 111. The annular plate 245 always blocks and seals the annular groove 114 during the revolution, so that the annular groove 114 is divided into cavity one 246 and cavity two 247 by the cross bar 24, and cavity one 246 and cavity two 247 are respectively connected to the circular holes 244 on both sides of the cross bar 24.

[0066] When the stirring effect needs to be improved, the control system switches the first spring 232 from the energized state to the de-energized state. After the de-energization, the first spring 232 gradually lengthens under its own elastic force, and the first spring 232 pushes the lifting plate 23 to move upward, so that the lifting plate 23 and the protrusion on the opposite side of the cam 22 are in contact.

[0067] When the protrusion on the cam 22 contacts the protrusion on the lifting plate 23, the cam 22 pushes the lifting plate 23 to move downward, and the lifting plate 23 compresses the first spring 232 at the same time. The lifting plate 23 drives the sliding shaft 243 to move downward through the annular groove, and the sliding shaft 243 slides downward in the limiting groove 211. The sliding shaft 243 drives the rack 242 to slide downward in the sliding groove 212, and the rack 242 drives the gear 241 to rotate, and the gear 241 drives the cross bar 24 to rotate, and the cross bar 24 drives the mixing plate 26 to rotate, so that the mixing plate 26 rotates while revolving, thereby improving the mixing effect of the mixing plate 26 on the preparation raw materials;

[0068] When the protrusion on the cam 22 and the protrusion on the lifting plate 23 are not in contact, the first spring 232 is released, and the first spring 232 pushes the lifting plate 23 to move upward. The lifting plate 23 drives the sliding shaft 243 to move upward through the annular groove, and the sliding shaft 243 drives the rack 242 to move upward. The rack 242 drives the gear 241 to rotate in the opposite direction. The gear 241 drives the mixing plate 26 to rotate in the opposite direction through the cross bar 24, and drives the lifting plate 23 to move up and down reciprocatingly through the cam 22, so that the mixing plate 26 can continuously rotate forward and reverse, thereby further improving the mixing effect of the preparation raw materials.

[0069] After the preparation raw materials are stirred and mixed, they need to be cooled. The control system controls the electromagnetic valves in the detection tube 13, the capillary tube 17 and the evaporation tube 12 to open, and the lifting plate 23 drives the upper cylinders in the telescopic plates A27 and B271 to move downward. The air pressure in the chamber formed between the upper cylinders in the telescopic plates A27 and B271, the lifting plate 23 and the diaphragm 273 increases. When the air pressure increases, the diaphragm 273 is squeezed downward to bend, so that the volume of the circulation chamber 272 decreases, and the refrigerant pressure in the circulation chamber 272 increases while the temperature rises. The displacement sensor on the lifting plate 23 feeds back the displacement data of the lifting plate 23 to the control system, and the diaphragm 273 squeezes the refrigerant in the circulation chamber 272 into the capillary tube 17. The multiple groups of refrigeration plates 171 and the ventilation system cooperate to realize the cooling treatment of the capillary tube 17, so that the temperature of the refrigerant in the capillary tube 17 is reduced and the refrigerant is converted from gas to liquid. After the liquid refrigerant passes through the expansion valve, the pressure is released and the temperature drops sharply, and it is converted from liquid to aerosol. The aerosol refrigerant passes through the expansion valve and enters the evaporation chamber. The refrigerant passes through the expansion valve and changes from liquid to gas. The gaseous refrigerant passes through the evaporator tube 12 and enters the cavity 246 in the annular groove 114, and enters the inside of the cross bar 24 from the annular groove 114 and the circular hole 244 on one side of the cross bar 24. The gaseous refrigerant is diverted from the inside of the cross bar 24 into the spiral flow channel 261 of the mixing plate 26. The gaseous refrigerant is heat exchanged with the preparation raw materials through the mixing plate 26. The temperature of the refrigerant increases after the heat exchange. Finally, the refrigerant is transported to the cavity 246 in the annular groove 114 through the circular hole 244 on the other side of the cross bar 24. In the cavity 247, the refrigerant is transported to the detection tube 13 through the cavity 247, and then the lifting plate 23 drives the upper cylinders in the telescopic plates A27 and B271 to move upward, and the air pressure in the chamber between the upper cylinders in the telescopic plates A27 and B271, the lifting plate 23 and the diaphragm 273 is reduced. After the air pressure is reduced, the diaphragm 273 is squeezed to bend upward, so that the volume of the circulation chamber 272 becomes larger, and the circulation chamber 272 draws the refrigerant in the detection tube 13 back into the circulation chamber 272 through the one-way valve, so that the refrigerant forms a circulation.

[0070] After mixing, the preparation raw materials are gradually dissolved and neutralized, and the control system opens the switch valve 116 on the partition 115, and introduces positive pressure gas into the feed pipe 14 through the pressurization system. After the positive pressure gas enters the sleeve 111, the positive pressure air pushes the preparation through the switch valve 116 on the partition 115 and is transported downward to the filter membrane. At this time, the pressure on the upper side of the filter membrane is greater than the pressure on the lower side, so that the dissolved preparation raw materials are transported downward faster and pass through the filter membrane on the filter 25, and are discharged from the discharge pipe 15 after being filtered by the filter membrane.

[0071] It will be apparent to those skilled in the art that the invention is not limited to the details of the exemplary embodiments described above and that the invention can be implemented in other specific forms without departing from the spirit or essential features of the invention. Therefore, the embodiments should be considered exemplary and non-limiting in all respects, and the scope of the invention is defined by the appended claims rather than the foregoing description, and it is intended that all variations falling within the meaning and range of equivalent elements of the claims be included in the invention. Any reference numeral in a claim should not be considered as limiting the claim to which it relates.

Claims

1. A stirring and neutralizing device for a melphalan hydrochloride preparation for injection, comprising a ventilation system and a control system, characterized in that: The invention comprises a cylinder (11), wherein a sleeve (111) is sleeved inside the cylinder (11), a horizontal plate (112) is arranged on the upper side of the sleeve (111), a partition plate (115) is arranged on the lower side of the sleeve (111), a plurality of groups of vertical plates (113) are arranged on the outer side of the sleeve (111), and a plurality of groups of annular grooves (114) are arranged in sequence on the inner side of the sleeve (111); a feed pipe (14) is connected to the upper side of the cylinder (11), the feed pipe (14) is connected to a pressurizing system, a discharge pipe (15) is connected to the lower side of the cylinder (11), a coil (16) is arranged inside the cylinder (11), a motor seat is installed on the cylinder (11), and a vertical A driving motor (2) is installed, and a transmission shaft (21) is installed in the sleeve (111); the upper end of the transmission shaft (21) passes through a transverse plate (112) and is connected to the output end of the driving motor (2); the lower end of the transmission shaft (21) passes through a partition plate (115) and is rotatably installed on the bottom of the cylinder (11) through a bearing; the interior of the transmission shaft (21) is hollow, and a cam (22) and a lifting plate (23) are installed on the upper side of the transmission shaft (21) in sequence; the cam (22) and the lifting plate (23) are located above the transverse plate (112), and a telescopic plate A (27) and a telescopic plate B (271) are installed between the lifting plate (23) and the transverse plate (112).

2. A stirring and neutralizing device for a melphalan hydrochloride preparation for injection according to claim 1, characterized in that: In the horizontal direction, a plurality of through grooves are arranged in the middle of the transmission shaft (21), a cross bar (24) is rotatably installed in the through groove, a gear (241) is arranged in the middle of the cross bar (24), rotating parts (248) are rotatably arranged at both ends of the cross bar (24), and the rotating parts (248) at both ends are inserted into the annular groove (114), and two groups of mixing plates (26) are installed on the cross bar (24), and the mixing plates (26) and the coil (16) cooperate to perform stirring and temperature control; in the vertical direction, a sliding groove (212) is arranged on the inner wall of the transmission shaft (21), a rack (242) is slidably installed in the sliding groove (212), and the gear (241) and the rack (242) are meshed; the transmission shaft A filter (25) is installed on the lower side of the cylinder (21); the cam (22) is located above the lifting plate (23); a plurality of protrusions are arranged on the opposite side of the cam (22) and the lifting plate (23); the cam (22) is installed on the transmission shaft (21); the lifting plate (23) slides on the inner wall of the cylinder (11); a displacement sensor is installed on the lifting plate (23); a guide shaft (231) is slidably installed on the lifting plate (23); the lower end of the guide shaft (231) is installed on the transverse plate (112); a first spring (232) is connected between the lifting plate (23) and the transverse plate (112); the first spring (232) is sleeved on the guide shaft (231); and the first spring (232) is electrically connected to the control system.

3. A stirring and neutralizing device for a melphalan hydrochloride preparation for injection according to claim 2, characterized in that: The middle part of the lifting plate (23) is hollowly sleeved on the transmission shaft (21); a circular groove is provided in the middle part of the lifting plate (23); sealing rings are provided between the lifting plate (23) and the transmission shaft (21) on both sides of the circular groove; sliding shafts (243) are provided at both ends of the rack (242); a limiting groove (211) is provided on the transmission shaft (21) directly facing the sliding shaft (243); and both ends of the sliding shaft (243) pass through the limiting groove (211) and are inserted into the circular groove.

4. A stirring and neutralizing device for a melphalan hydrochloride preparation for injection according to claim 3, characterized in that: The cross bar (24) and the rotating part (248) are hollow inside, and the rotating parts (248) on both sides are provided with circular holes (244). The circular holes (244) on the rotating parts (248) on both sides are respectively located on opposite sides. Circular plates (245) are installed at both ends of the cross bar (24), and the circular plates (245) block and seal the annular groove (114). The circular plates (245) are rotatably installed on the inner wall of the sleeve (111). A cavity is formed between the annular groove (114) and the circular plates (245), and the cross bar (24) divides the cavity into cavity one (246) and cavity two (247).

5. A stirring and neutralizing device for a melphalan hydrochloride preparation for injection according to claim 4, characterized in that: The telescopic plate A (27) is located outside the telescopic plate B (271), and the telescopic plate A (27) and the telescopic plate B (271) are both composed of an upper cylinder and a lower cylinder sleeved together, and the upper cylinder and the lower cylinder form a sliding sealing connection, and the lower cylinders in the telescopic plate A (27) and the telescopic plate B (271) are both installed on the horizontal plate (112), and a diaphragm (273) is connected between the lower cylinders in the telescopic plate A (27) and the telescopic plate B (271), and the upper cylinders on the telescopic plate A (27) and the telescopic plate B (271) are both installed on the lifting plate (23); A circulation chamber (272) is formed between the lower cylinder, the diaphragm (273) and the transverse plate (112) in the telescopic plate A (27) and the telescopic plate B (271), and a refrigerant is provided in the circulation chamber (272).

6. A stirring and neutralizing device for a melphalan hydrochloride preparation for injection according to claim 5, characterized in that: The vertical plate (113) is located between the sleeve (111) and the cylinder (11), and the vertical plate (113) divides the space between the sleeve (111) and the cylinder (11) into a plurality of sectors, wherein the evaporation tube (12) and the detection tube (13) are respectively installed in two opposite sectors; The evaporation tube (12) and the detection tube (13) are both mounted on the sleeve (111); the inlet of the evaporation tube (12) is connected to a capillary tube (17) through a regulating valve and an expansion valve in sequence; a plurality of groups of refrigeration plates (171) are mounted inside the capillary tube (17); the plurality of groups of refrigeration plates (171) are tightly mounted on the capillary tube (17); the capillary tube (17) is connected to the interior of the lower cylinder in the telescopic plate A (27); the capillary tube (17) is mounted on the horizontal plate (112); and the outlet of the evaporation tube (12) passes through the sleeve (111) and is connected to the interior of the plurality of groups of annular grooves (114); The inlet of the detection tube (13) passes through the sleeve (111) and is communicated with the annular groove (114); the outlet of the detection tube (13) is communicated with the interior of the lower cylinder in the telescopic plate A (27); and a one-way valve, a solenoid valve and a temperature sensor are installed in series in the detection tube (13), the capillary tube (17) and the evaporation tube (12).

7. A stirring and neutralizing device for a melphalan hydrochloride preparation for injection according to claim 6, characterized in that: The inner diameter of the capillary tube (17) is smaller than the inner diameter of the evaporation tube (12); an air inlet (18) and an air outlet (181) are provided on the cylinder (11) near the capillary tube (17); the air inlet (18) is located on one side of the air outlet (181); the air inlet (18) is connected to a ventilation system; and the air outlet (181) is connected to the external atmosphere; The capillary tube (17) is distributed in a transverse spiral, and the evaporation tube (12) and the detection tube (13) are distributed in a longitudinal spiral.

8. A stirring and neutralizing device for a melphalan hydrochloride preparation for injection according to claim 7, characterized in that: A plurality of groups of temperature difference plates A (121) are installed on the inner wall of the evaporation tube (12), and a plurality of groups of temperature difference plates B (131) are installed on the inner wall of the detection tube (13). The plurality of groups of temperature difference plates A (121) and the plurality of groups of temperature difference plates B (131) correspond to each other one by one. The temperature difference plates A (121), the temperature difference plates B (131) and the refrigeration plate (171) are all provided with semiconductors of two different materials and a metal plate. One end of the semiconductors of the two different materials is connected to the metal plate. The two semiconductors on the temperature difference plate A (121) and the two semiconductors on the temperature difference plate B (131) are connected by wires, one of which is connected to a control system. The two semiconductors on the refrigeration plate (171) are electrically connected to the control system by wires.

9. A stirring and neutralizing device for a melphalan hydrochloride preparation for injection according to claim 8, characterized in that: The mixing plate (26) is made of a spiral twist, and a plurality of spiral flow channels (261) are arranged inside the mixing plate (26), and the plurality of spiral flow channels (261) are arranged along the spiral of the mixing plate (26), and the inlets and outlets of the plurality of spiral flow channels (261) are connected to the inside of the crossbar (24); a metal material (262) is arranged outside the mixing plate (26), and the metal material (262) is in the magnetic field of the coil (16); Another set of temperature sensors and an electronic pH meter are installed in the sleeve (111); a switch valve (116) is installed on the partition (115); the switch valve (116), the other set of temperature sensors and the electronic pH meter are all electrically connected to the control system; the middle part of the filter (25) is rotatably sealed with the transmission shaft (21); the filter (25) is installed on the sleeve (111); and a filter membrane is provided on the filter (25); a control panel (1) is installed on the cylinder (11); the control system is provided in the control panel (1); and an encoder is built into the drive motor (2).

10. A stirring neutralization method for a melphalan hydrochloride preparation for injection, characterized in that: A stirring and neutralizing device for a melphalan hydrochloride preparation for injection is used, and the stirring and neutralizing method includes the following: S1, adding a certain amount of water for injection into the sleeve (111) and stirring; S2. Add sodium sulfobutyl beta-cyclodextrin while stirring, and stir to dissolve; S3, cooling the preparation in the sleeve (111) to 2-8°C; S4, adding melphalan hydrochloride while stirring, and stirring again to dissolve; S5. Add sodium hydroxide solution and hydrochloric acid solution while stirring to adjust the pH value to within the range specified by the process; S6. Add water for injection at a temperature not exceeding 25°C while stirring and continue stirring evenly; S7. After filtering, the desired preparation is obtained.

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