Oscillating water distillation apparatus for the preparation of complex injectables

Abstract

The present application relates to the technical field of pharmaceutical equipment, and particularly relates to a kind of oscillation type reduced pressure distillation waterization equipment for preparing complex injection, such as micelle, liposome, microsphere and the like, which comprises: oscillation cavity, multiple partitions are arranged in the oscillation cavity, vibration device is arranged at the bottom of the oscillation cavity, for wave type or hinged plate type vibration of the oscillation cavity;Evaporation box, the evaporation box is the cavity structure arranged on each partition, the bottom of any one end is provided with a discharge interface, the top is connected with the vacuum feed pipe penetrating the outer wall of the oscillation cavity, the vacuum feed pipe is connected with the valve pipeline connected with the vacuum pump through the interface;In addition, the evaporation box is provided with a heater at the bottom.The present application uses multiple evaporation boxes to replace rotary evaporation round bottom flask, expands the one-time evaporation capacity, realizes the scale-up production of related pharmaceutical preparations in industrial production, forms ideal film layer at the bottom of the box by vacuum pump and heater, and also integrates the whole preparation method of film waterization into the equipment, avoids the risk of material pollution in transfer.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of pharmaceutical equipment, in particular to an oscillation type reduced pressure distillation hydration equipment for preparing complex injection. BACKGROUND

[0002] The thin film hydration method is a classic preparation method for high-end complex drug preparations such as liposomes and micelles. Specifically, the carrier material and the drug are dissolved by an organic reagent, and then the solution is placed in a round-bottom flask. The material forms a thin film on the inner wall of the flask after rotary evaporation under reduced pressure. Then a certain amount of buffer solution is added, and the flask is shaken to make the thin film hydrate and fall off, forming a uniform liquid, and then forming the preparation.

[0003] The thin film hydration method includes two processes of film evaporation and oscillation hydration. The essence of the film evaporation process is to remove the organic reagent by reduced pressure distillation, leaving a solid thin film layer. At present, the film evaporation process is completed by using a rotary evaporator. Due to the limitation of the volume of the rotary evaporation flask, the preparation amount of this process is quite limited. In order to realize mass production, production enterprises often use multiple rotary evaporators to divide the same batch of products into different rotary evaporators for rotary evaporation. After rotary evaporation, the rotary evaporation flask is disassembled and transferred to the hydration equipment. The whole process is complex and tedious, and the quality of the same batch of drugs is also uneven. From the safety point of view, large-volume rotary evaporation flasks are usually used in industrial production. Considering that the rotary evaporation flask is made of glass and contains organic reagents inside, this process can easily induce safety accidents. SUMMARY

[0004] The present application provides an oscillation type reduced pressure distillation hydration equipment for preparing complex injection. The present application uses multiple evaporation boxes instead of rotary evaporation round-bottom flasks, which expands the one-time evaporation capacity and realizes the scale-up production of related drug preparations in industrial production. Through the vacuum pump and the heater, an ideal thin film layer is formed at the bottom of the box, and the whole preparation method of thin film hydration is also integrated into the equipment, avoiding the risk of contamination of the material during transfer.

[0005] In order to achieve the above object, the present application provides the following technical scheme: an oscillation type reduced pressure distillation water preparation equipment for preparing complex injection, comprising: an oscillation cavity, a plurality of partitions are arranged in the oscillation cavity, and a vibration device is arranged outside the oscillation cavity, the vibration device comprises a plurality of telescopic supports and a control device, and is used for wave type or waver type vibration of the oscillation cavity; an evaporation box, the evaporation box is a cavity structure arranged on each partition, a discharge interface is arranged at the bottom of any end of the evaporation box, a vacuum feeding pipe penetrating through the outer wall of the oscillation cavity is connected to the top of the two ends of the evaporation box, the vacuum feeding pipe is connected with a valve pipe connected with a vacuum pump through an interface, and a heater is arranged at the bottom of the evaporation box; a vacuum pump, the vacuum pump is connected with the vacuum feeding pipe through the valve pipe; and a pressure balance port is further arranged at the top of the evaporation box, and a pressure valve is arranged in the pressure balance port.

[0006] Preferably, the valve pipe comprises a feeding pipe fixedly arranged at the two ends of the oscillation cavity; the feeding pipe is provided with a plurality of branch pipes connected with the interfaces of the vacuum feeding pipes respectively, each branch pipe is provided with a first valve, one end of the feeding pipe is connected with the vacuum pump through an exhaust valve, and a feeding port is arranged at the end of the feeding pipe away from the exhaust valve, and the feeding port is provided with a feeding valve.

[0007] Preferably, the branch pipe adopts an elastic bellows structure.

[0008] Preferably, the branch pipe and the vacuum feeding pipe are detachably connected.

[0009] Preferably, a cold trap is arranged between the exhaust valve and the vacuum pump.

[0010] Preferably, the vibration device comprises a pedestal arranged below the oscillation cavity, and a plurality of telescopic cylinders vertically arranged on the top of the pedestal, the telescopic ends of each telescopic cylinder are connected with the bottom of the oscillation cavity, and each telescopic cylinder is connected with a hydraulic pump through a control valve group.

[0011] Preferably, the telescopic cylinder comprises a first telescopic cylinder arranged on one side of the oscillation cavity and a second telescopic cylinder arranged on the other side of the oscillation cavity, the telescopic end of each first telescopic cylinder is hingedly connected with the bottom of the oscillation cavity, the telescopic end of each second telescopic cylinder is hingedly connected with the bottom of the oscillation cavity through a hinge arm, and each first telescopic cylinder and each second telescopic cylinder are arranged in parallel.

[0012] Preferably, each of the partition top is provided with a sliding rail, the evaporation box is matched with the sliding rail through a sliding block, and the evaporation box is connected with the inner wall of the oscillation cavity through a tension spring at both ends; the wave vibration device further comprises a compound pneumatic piston vibrator fixedly arranged at the end of each evaporation box in the axial direction, and the compound pneumatic piston vibrator is connected with an external air source device through a high-pressure pipe penetrating the outer wall of the oscillation cavity.

[0013] Preferably, the evaporation box is internally provided with a plurality of baffle plates perpendicular to the bottom plate, and the top of the baffle plate is spaced from the inner wall of the evaporation box.

[0014] Preferably, the heater is electrically connected with a control power supply through a cable penetrating the outer wall of the oscillation cavity.

[0015] The present application has the following advantages:

[0016] 1. The evaporation box adopts a wide-bottom-area box to replace a rotary evaporation round-bottom flask, the volume of the solution added into the box is controlled, and under the action of a vacuum pump and a heater, an ideal thin film layer can be formed at the bottom of the box under the condition of constant-temperature reduced-pressure distillation. The traditional rotary evaporation process is converted into a wave vibration evaporation film forming process, the demand for rotary power devices is reduced in large-scale equipment, the energy saving effect is achieved, and the safety of the preparation process is improved.

[0017] 2. By increasing the bottom area of the evaporation box and the number of evaporation boxes, the scale-up production of related pharmaceutical preparations in industrial production is realized, and the problem that the evaporation film forming by using a rotary evaporator in the traditional method is difficult to scale up in industrial production is solved. The whole preparation method of thin film hydration is also integrated into the equipment, so that the preparation process is simplified, and the risk of contamination of the material in the transfer is avoided.

[0018] 3. The vacuum pump directly performs vacuumizing on each evaporation box through a pipeline, instead of performing vacuumizing on the whole cavity of the equipment, which not only improves the vacuumizing efficiency, but also avoids the corrosion of organic reagents to the inner wall of the equipment and the leakage of organic reagents. The evaporation box realizes three-axis six-direction reciprocating motion under the cooperation of the oscillation cavity, thereby improving the film forming efficiency. BRIEF DESCRIPTION OF DRAWINGS

[0019] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or prior art description. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can also be obtained by those skilled in the art without creative labor.

[0020] Figure 1 It is a schematic view of the valve pipeline and the evaporation box connection structure of the present application.

[0021] Figure 2 Fig. 1 is a schematic diagram of the internal structure of one end of the oscillation cavity of the present application;

[0022] Figure 3 Fig. 2 is a schematic diagram of the internal structure of one side of the oscillation cavity of the present application. DETAILED DESCRIPTION

[0023] The technical solutions of the present application will be described clearly and completely below in combination with the drawings of the present application. Obviously, the described embodiments are only some of the embodiments of the present application, but not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0024] According to Figure 1 , Figure 2 , Figure 3 As shown in Fig. 1, an oscillation type reduced pressure distillation water preparation equipment for complex injection preparation comprises an oscillation cavity 1, a plurality of partitions 2 are arranged in the oscillation cavity 1, and the oscillation cavity 1 is provided with wave vibration devices; an evaporation box 3, which is a cavity structure arranged on each partition 2, and the bottom of any one end of the evaporation box 3 is provided with a discharge interface 4, the top of both ends of the evaporation box 3 is connected and provided with vacuum feeding pipes 5, the vacuum feeding pipes are all penetrated through the outer wall of the oscillation cavity 1 through interfaces and connected with valve pipelines, and the bottom of the evaporation box 3 is provided with a heater 7; a vacuum pump 8, which is connected with the vacuum feeding pipes 5 through the valve pipelines. The top of the evaporation box 3 is further provided with a pressure balance port, the pressure balance port is provided with a pressure valve 25, which is used for releasing the pressure in the evaporation box 3. Wherein, a plurality of column plates 23 perpendicular to the bottom plate can be arranged in the evaporation box 3, which makes the mixing and heat transfer of the internal substances of the evaporation box 3 more uniform during the water preparation process. The heater 7 is electrically connected with a control power supply through cables penetrated through the outer wall of the oscillation cavity 1, and in addition, the heater 7 can also realize the heating function in a fluid circulation mode.

[0025] In the setting, the evaporation box 3 adopts a box body with a wide bottom area instead of a rotary evaporation round bottom flask, by controlling the volume of the solution added into the box body, under the action of the vacuum pump 8 and the heater 7, an ideal thin film layer can be formed at the bottom of the box body under the condition of constant temperature and reduced pressure distillation. Meanwhile, by increasing the bottom area of the evaporation box 3 and the number of the evaporation boxes 3, the scale-up production of related drug preparations in industrial production can be realized, and the problem that the evaporation and film formation using the rotary evaporation instrument in the traditional method is difficult to be scaled up in industrial production is solved.

[0026] In addition, the equipment also integrates the whole preparation method of the thin film water preparation, so that the preparation process is simplified, and the risk of contamination of the materials in the transfer is avoided.

[0027] The valve pipeline comprises a feed pipe 9 fixedly arranged at both ends of the oscillation cavity 1; the feed pipe 9 is provided with a plurality of branch pipes 10 respectively connected with the interfaces of the vacuum feed pipe 5, the branch pipes 10 are realized by high-pressure hoses, and each branch pipe 10 is provided with a first valve 11; one end of the feed pipe 9 is connected with the vacuum pump 8 through an exhaust valve 12; and one end of the feed pipe 9 away from the exhaust valve 12 is provided with a feed port, and the feed port is provided with a feed valve 14.

[0028] In this arrangement, the cooperation of the first valve 11, the exhaust valve 12 and the feed valve 14 realizes the feeding of a single evaporation tank 3 and the negative pressure distillation operation; the vacuum pump 8 can individually vacuumize each evaporation tank 3, instead of vacuumizing the entire cavity of the equipment, which not only improves the vacuumizing efficiency, but also avoids the corrosion of the organic reagent to the inner wall of the equipment and the leakage of the organic reagent.

[0029] The cold trap 15 is arranged between the exhaust valve 12 and the vacuum pump 8, and is used for collecting the discharged organic reagent to protect the vacuum pump 8.

[0030] In order to enable the evaporation tank 3 to vibrate in multiple spatial dimensions, the wave vibration device comprises a pedestal 16 arranged below the oscillation cavity 1, and a plurality of telescopic cylinders longitudinally arranged on the top of the pedestal 16; the telescopic end of each telescopic cylinder is connected with the bottom of the oscillation cavity 1, and each telescopic cylinder is connected with a hydraulic pump through a control valve group, for the swing plate type vibration of the oscillation cavity; and the telescopic cylinder can be selected as a pneumatic cylinder, an electric cylinder or a hydraulic cylinder according to the requirement.

[0031] The telescopic cylinder comprises a first telescopic cylinder 17 arranged at one side of the oscillation cavity 1 and a second telescopic cylinder 18 arranged at the other side of the oscillation cavity 1; the telescopic end of each first telescopic cylinder 17 is hingedly connected with the bottom of the oscillation cavity 1, and the telescopic end of each second telescopic cylinder 18 is hingedly connected with the bottom of the oscillation cavity 1 through a hinged arm 24; and each first telescopic cylinder 17 and each second telescopic cylinder 18 are arranged in parallel.

[0032] In addition, the top of each partition plate 2 is provided with a sliding rail 20, the evaporation tank 3 is matched with the sliding rail 20 through a sliding block 19, and the two ends of the evaporation tank 3 are connected with the inner wall of the oscillation cavity 1 through a tension spring 21; the wave vibration device further comprises a compound pneumatic piston vibrator 22 fixedly arranged at the end of each evaporation tank 3 along the axial direction, and the compound pneumatic piston vibrator 22 is connected with an external air supply device through a high-pressure pipe penetrating the outer wall of the oscillation cavity 1.

[0033] With the above settings, the evaporator 3, in conjunction with the oscillation chamber 1, achieves triaxial and six-directional reciprocating motion, thereby improving film formation efficiency.

[0034] In practical applications, it includes two working stages: the evaporation film formation stage and the hydration stage.

[0035] In the evaporation film formation stage, the feed pipe 9 is first connected to the evaporation box. The solution is added to the evaporation box 3 by opening the feed valve 14 to complete the feeding. Then, the evaporation box 3 is heated by the heater 7. After that, the vacuum pump 8 is started and the exhaust valve 12 is opened to carry out depressurized evaporation. At the same time, the pressure inside the evaporation box 3 is balanced by controlling the pressure valve 25. Since the evaporation box 3 has a transparent observation hole 26, the material inside the evaporation box 3 can be observed.

[0036] After vacuum distillation is complete, the solute forms a uniform film at the bottom of the evaporator 3. The vacuum pump 8 and exhaust valve 12 are then closed, and the feed valve 14 is opened to allow the hydration medium to be fed into the evaporator 3 through the feed pipe 9. Since the evaporator is under negative pressure at this time, rapid material intake is achieved. After feeding is complete, the feed valve 14 is closed, and the evaporator's wave vibration device is activated, while the heater 7 is controlled to enter a constant-temperature oscillation mode until a stable and uniform micelle solution is formed. Finally, the hydrated solution is collected through the discharge port 4 and transferred to the next unit for subsequent processes.

[0037] After the process is completed, the cleaning solution is fed into the evaporator 3 through the feed pipe. After cleaning, it is discharged from the outlet. In addition, the heater 7 can be turned on to perform high-temperature steam sterilization on the evaporator. After sterilization, the pressure valve 25 is used to release the pressure in the evaporator.

[0038] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A vibratory vacuum distillation hydration apparatus for preparing complex injectable drugs, characterized in that... ,include: An oscillation chamber is provided with multiple partitions inside, and a slide rail is provided on the top of the partitions; An evaporator is a cavity structure disposed on each of the partitions. The evaporator is slidably connected to the slide rail via a slider, and both ends of the evaporator are connected to the inner wall of the oscillation chamber via tension springs. The bottom of any one end of the evaporator is provided with a discharge port, and the top of both ends of the evaporator are connected to a vacuum feed pipe that penetrates the outer wall of the oscillation chamber. The vacuum feed pipe is connected to a valve pipeline connected to a vacuum pump through an interface. The bottom of the evaporator is equipped with a heater; The evaporator is equipped with several partitions perpendicular to the bottom plate inside, and the top of the partitions is spaced apart from the inner wall of the evaporator. The top of the evaporator is provided with a pressure balancing port, and a pressure valve is provided inside the pressure balancing port; Vibration device, including: A platform spaced below the oscillation cavity; Multiple telescopic cylinders are longitudinally arranged on the top of the platform, with the telescopic end of each telescopic cylinder connected to the bottom of the oscillation chamber, and each telescopic cylinder is connected to a hydraulic pump through a control valve group. A compound pneumatic piston vibrator is fixedly installed at the end of each of the evaporators along the axial direction. The compound pneumatic piston vibrator is connected to an external air source device through a high-pressure pipe that penetrates the outer wall of the oscillation chamber. The vibration device is used to drive the oscillation cavity to perform wave-like or rocker-like vibrations, and to enable the evaporator to achieve triaxial six-axis composite vibration.

2. The oscillating vacuum distillation hydration apparatus for preparing complex injections according to claim 1, characterized in that: The valve pipeline includes a feed pipe fixedly installed at both ends of the oscillation chamber; the feed pipe is provided with multiple branch pipes respectively connected to the interface of the vacuum feed pipe, and each branch pipe is provided with a first valve; one end of the feed pipe is connected to the vacuum pump through an exhaust valve; the end of the feed pipe away from the exhaust valve is provided with a feed port, and the feed port is provided with a feed valve.

3. The oscillating vacuum distillation hydration apparatus for preparing complex injections according to claim 2, characterized in that, The branch pipe adopts an elastic corrugated pipe structure.

4. The oscillating vacuum distillation hydration apparatus for preparing complex injections according to claim 2, characterized in that: A cold trap is provided between the exhaust valve and the vacuum pump.

5. The oscillating vacuum distillation hydration apparatus for preparing complex injections according to claim 1, characterized in that: The telescopic cylinder includes a first telescopic cylinder disposed on one side of the oscillation cavity and a second telescopic cylinder disposed on the other side of the oscillation cavity. The telescopic end of each first telescopic cylinder is hinged to the bottom of the oscillation cavity, and the telescopic end of each second telescopic cylinder is hinged to the bottom of the oscillation cavity through a hinge arm. Each first telescopic cylinder and each second telescopic cylinder are respectively arranged in parallel.

6. The oscillating vacuum distillation hydration apparatus for preparing complex injections according to claim 1, characterized in that: The heater is electrically connected to the control power supply via a cable that passes through the outer wall of the oscillation cavity.

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