CN113713748A

CN113713748A - Automatic liquid preparation synthesizer for medicinal nucleic acid

Info

Publication number: CN113713748A
Application number: CN202110938747.1A
Authority: CN
Inventors: 雍金贵; 刘宗文; 潘红; 朱桃花; 武新春
Original assignee: General Biology Anhui Co ltd
Current assignee: General Biology Anhui Co ltd
Priority date: 2021-08-16
Filing date: 2021-08-16
Publication date: 2021-11-30
Anticipated expiration: 2041-08-16
Also published as: CN113713748B

Abstract

The invention relates to an automatic liquid preparation synthesizer for medicinal nucleic acid, which belongs to the technical field of pharmaceutical equipment, divides the synthesis process of nucleic acid into three steps of liquid preparation, quantitative heating and liquid injection and oscillation synthesis, integrates a material preparation device, a liquid injection device, an oscillation seat device and a synthesis assembly on a bracket, and circularly conveys the materials by an annular conveyor, has simple structure, realizes the streamlined industrial production of the synthesis and liquid preparation of the medicinal nucleic acid, and solves the technical problems of small yield of the medicinal nucleic acid, low yield and high labor cost investment in the prior art; the feeding and synthesizing processes of the synthesizer are all finished in a closed environment, the contact with the external environment is less, on one hand, the output stability of the product is high, on the other hand, the requirement on the production environment is not harsh, a large amount of capital is not required to be invested to construct a high-level sterile workshop, and the production cost is reduced.

Description

Automatic liquid preparation synthesizer for medicinal nucleic acid

Technical Field

The invention belongs to the technical field of pharmaceutical equipment, and particularly relates to an automatic liquid preparation synthesizer for medicinal nucleic acid.

Background

The nucleic acid medicine is also called as nucleotide medicine, is various oligoribonucleotide or oligodeoxyribonucleotide with different functions, mainly plays a role in gene level and has wide application prospect.

In the prior art, the preparation of nucleic acid drugs is mainly synthesized in a manual operation mode, and the following problems exist:

1. the artificial synthesis yield is small, the yield is low, and the manpower input is large;

2. in the synthesis process of nucleic acid, in order to prevent pollution, a high-grade sterile workshop needs to be established, a large amount of infrastructure and later-stage operation cost are needed, the quality of manual liquid adding is difficult to guarantee, and the stability of each batch of medicine is difficult to guarantee.

Disclosure of Invention

In order to overcome the technical problems mentioned in the background art, the invention aims to provide an automatic liquid preparation synthesizer for medicinal nucleic acid.

The purpose of the invention can be realized by the following technical scheme:

an automatic liquid preparation synthesizer for medicinal nucleic acid comprises a rack, wherein an electric cabinet is arranged at the bottom of the rack, an annular conveyor is arranged in the middle of the rack, and a control cabinet is arranged at the top of the bottom of the rack;

the automatic liquid filling device is characterized in that a batching device is arranged in the control cabinet, a suspension bracket is fixedly arranged below the control cabinet, a liquid filling device is arranged on the suspension bracket, an oscillating seat device is arranged on the annular conveyor, and a synthesis assembly is arranged in the oscillating seat device.

Further, the dosing unit is including mixing the liquid pipe and setting up in the pipe support that is used for fixed liquid pipe that mixes outside the liquid pipe, the interior diapire fixed connection of this pipe support and switch board, be provided with a plurality of stoste joints that communicate with mixing the inside of liquid pipe on the lateral wall of mixing the liquid pipe, and the stoste joint communicates the liquid pipe respectively, all be provided with the flowmeter and the solenoid valve that are used for controlling stoste feed liquor volume on the liquid pipe, the top thread sealing connection who mixes the liquid pipe has the tube cap, ultrasonic generator is installed at the top of tube cap, ultrasonic generator's output is connected with the ultrasonic vibration stick that extends to mixing the inside of liquid pipe, make stoste homogeneous mixing through ultrasonic vibration.

Further, be provided with level gauge and pressure sensor on the lateral wall of mixing the liquid pipe, level gauge and pressure sensor's sense terminal is located the inside of mixing the liquid pipe, it still is provided with supplementary row material subassembly to mix the liquid pipe, this supplementary row material subassembly including set up in the tube cap edge and with the pressure joint of mixing the inside intercommunication of liquid pipe, and the two-way air pump of pressure joint intercommunication, the bottom of mixing the liquid pipe is provided with the fluid-discharge tube that mixes the liquid pipe intercommunication, be provided with flowmeter and the solenoid valve that is used for controlling the mixed liquid of quantitative discharge on the fluid-discharge tube, during the batching, gas in the liquid pipe is mixed to the external extraction to the two-way air pump, let in synthetic stoste to mixing the liquid pipe from stoste joint, during the flowing back, aseptic air is gone into to the continuous pump in mixing the liquid pipe to two-way air pump, the pressure of mixed liquid is maintained, mixed liquid is discharged with stable pressure, make the flowmeter measurement accurate, guarantee the flowing back precision.

Further, the liquid injection device comprises a liquid distribution pipe and an electric push rod above the liquid distribution pipe, the liquid distribution pipe penetrates through the suspension bracket, the outer side wall of the liquid distribution pipe and the suspension bracket are slidably mounted through a sliding sleeve, the electric push rod is fixedly mounted with the top wall of the suspension bracket through a support, the top end of the liquid distribution pipe is in threaded sealing connection with an impact top cover, an output shaft of the electric push rod coincides with the central axis of the impact top cover, a first spring is sleeved outside the liquid distribution pipe and is positioned between the bottom wall of the impact top cover and the top surface of the suspension bracket, a first quick connector communicated with the inside of the liquid distribution pipe is arranged at the bottom of the liquid distribution pipe, an electromagnetic valve is arranged on the liquid injection pipe, an interlayer is arranged in the pipe wall of the liquid distribution pipe, a heating wire is arranged in the interlayer, a liquid inlet pipe communicated with the inside of the liquid distribution pipe is arranged on the side wall of the impact top cover, the liquid inlet pipe is communicated with a liquid discharge pipe, and an auxiliary discharge assembly similar to the batching device is further arranged on the impact top cover, still be provided with temperature sensor on the lateral wall of liquid distribution pipe, inside temperature sensor's sense terminal was located liquid distribution pipe, through dosing unit ration flowing back and leading-in mixed liquid in liquid distribution pipe through the feed liquor pipe, the heating wire will be mixed liquid heating to synthetic temperature, and electric putter drive liquid distribution pipe is annotated downwards.

Further, the oscillating base device includes the installation shell, the inside relative both sides of installation shell all are provided with inner panel and planking, inner panel and planking are connected through flexible guide arm, and the outside cover of flexible guide arm is equipped with the second spring, the upper and lower both sides of the lateral wall of the relative installation shell of planking all are provided with the plunger hole, the downthehole fore-set that is provided with of plunger, the one end of fore-set extends to the installation shell outside, the other end of fore-set passes through boss swing joint with the lateral wall of planking, correspondingly, the cylinder is all installed to the upper and lower both sides of ring conveyor, and the mounting height in the output shaft of cylinder equals respectively with the mounting height in plunger hole.

Furthermore, the synthesis assembly comprises a synthesis pipe and a base arranged in the synthesis pipe, a pipe seat is arranged at the top end of the synthesis pipe, a second quick connector matched with the first quick connector is arranged in the pipe seat, a one-way air valve communicated with the outer side of the synthesis pipe is also arranged on the pipe seat, a sewage discharge pipe communicated with the synthesis pipe is arranged at the bottom of the synthesis pipe, a sewage suction connector is arranged on the sewage discharge pipe, and a synthesis column is clamped on the base; and injecting the heated mixed solution into a synthesis tube to synthesize nucleic acid, thereby completing the synthesis of the prepared solution.

Furthermore, the synthesis pipe is a heat preservation pipe with a vacuum interlayer arranged in the pipe wall, so that heat loss is reduced.

Furthermore, one side of the control cabinet is also provided with a feeding device which comprises a rack fixedly arranged with the frame, the rack is provided with a plurality of raw liquid tanks for holding synthetic raw materials, and the raw liquid tanks are communicated with the liquid distribution pipe.

The invention has the beneficial effects that:

1. the invention provides an automatic liquid preparation synthesizer for medicinal nucleic acid, which divides the synthesis process of nucleic acid into three steps of liquid preparation, quantitative heating and liquid injection and oscillation synthesis, realizes the streamlined industrial production of nucleic acid through a material preparation device, a liquid injection device, an oscillation seat device and a synthesis assembly, and solves the technical problems of small yield, low yield and high labor cost investment of medicinal nucleic acid in the prior art.

2. According to the automatic liquid preparation synthesizer for medicinal nucleic acid, the feeding and synthesizing processes are finished in a closed environment, the contact with the external environment is less, on one hand, the output stability of the product is high, on the other hand, the requirement on the production environment is not strict, a large amount of capital is not required to construct a high-level sterile workshop, and the production cost is reduced.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art that other drawings can be obtained according to the drawings without creative efforts.

FIG. 1 is a schematic view of an automatic liquid preparation synthesizer for medicinal nucleic acid according to the present invention;

FIG. 2 is a schematic structural view of a dispensing unit;

FIG. 3 is a schematic structural view of the liquid injection device;

FIG. 4 is a schematic structural diagram of an oscillating base device;

FIG. 5 is a schematic diagram of a composite assembly.

In the drawings, the components represented by the respective reference numerals are listed below:

10. a frame; 11. a cylinder; 12. an endless conveyor; 13. a rack; 14. a stock solution tank; 15. a liquid distribution pipe; 16. a control cabinet; 17. a suspension bracket; 18. an electrical cabinet; 20. a dosing device; 21. a pipe frame; 22. a liquid mixing pipe; 23. a dope joint; 24. an ultrasonic generator; 25. a tube cover; 26. an ultrasonic vibrating rod; 27. a liquid discharge pipe; 30. a liquid injection device; 31. a liquid separating pipe; 32. impacting the top cover; 33. an electric push rod; 34. a liquid inlet pipe; 35. a first spring; 36. an electric heating wire; 37. a first quick coupling; 40. an oscillation base device; 41. mounting a shell; 42. an outer plate; 43. an inner plate; 44. a second spring; 45. a top pillar; 50. a synthesis component; 51. synthesizing a tube; 52. a tube holder; 53. a second quick coupling; 54. synthesizing a column; 55. a base; 56. a sewage discharge pipe.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Referring to fig. 1-5, the invention is an automatic liquid preparation synthesizer for medicinal nucleic acid, comprising a frame 10, an electrical cabinet 18 is arranged at the bottom of the frame 10, an annular conveyor 12 is arranged in the middle of the frame 10, and a control cabinet 16 is arranged at the top of the bottom of the frame 10;

the batching device 20 is arranged in the control cabinet 16, the suspension bracket 17 is fixedly arranged below the control cabinet 16, the liquid injection device 30 is arranged on the suspension bracket 17, the oscillating seat device 40 is arranged on the annular conveyor 12, and the synthesis assembly 50 is arranged in the oscillating seat device 40.

Dosing unit 20 is used for fixed pipe support 21 that mixes liquid pipe 22 including mixing liquid pipe 22 with setting up in mixing the liquid pipe 22 outside, this

pipe support

21 and 16 inner diapire fixed connection of switch board, be provided with a plurality of stoste joints 23 with the inside intercommunication of mixing liquid pipe 22 on the lateral wall of mixing liquid pipe 22, and stoste joint 23 communicates respectively and joins in marriage liquid pipe 15, all be provided with flowmeter and the solenoid valve that is used for controlling stoste feed liquor volume on joining in marriage liquid pipe 15, the top screw thread sealing connection who mixes liquid pipe 22 has tube cap 25, ultrasonic generator 24 is installed at the top of tube cap 25, ultrasonic generator 24's output is connected with and extends to the inside ultrasonic vibration stick 26 of mixing liquid pipe 22, make stoste homogeneous mixing through ultrasonic vibration.

A liquid level meter and a pressure sensor are arranged on the side wall of the liquid mixing pipe 22, the detection ends of the liquid level meter and the pressure sensor are positioned inside the liquid mixing pipe 22, the liquid mixing pipe 22 is also provided with an auxiliary discharging component, the auxiliary discharging assembly includes a pressure joint disposed at the edge of the tube cover 25 and communicated with the interior of the liquid mixing tube 22, and a bidirectional air pump communicated with the pressure joint, a liquid discharge pipe 27 communicated with the liquid mixing pipe 22 is arranged at the bottom of the liquid mixing pipe 22, a flow meter and an electromagnetic valve for controlling the quantitative discharge of the mixed liquid are arranged on the liquid discharge pipe 27, when in material mixing, the two-way air pump pumps the air in the liquid mixing pipe 22 to the outside, the synthetic stock solution is led into the liquid mixing pipe 22 from the stock solution joint 23, during liquid discharge, the two-way air pump continues to pump into sterile air in mixing liquid pipe 22, maintains the pressure of mixed liquid, and mixed liquid discharges with stable pressure for the flowmeter measurement is accurate, guarantees the flowing back precision.

The liquid injection device 30 comprises a liquid separation pipe 31 and an electric push rod 33 above the liquid separation pipe 31, the liquid separation pipe 31 penetrates through the suspension bracket 17, the outer side wall of the liquid separation pipe 31 is slidably mounted with the suspension bracket 17 through a sliding sleeve, the electric push rod 33 is fixedly mounted with the top wall of the suspension bracket 17 through a support, the top end of the liquid separation pipe 31 is hermetically connected with an impact top cover 32 through threads, the output shaft of the electric push rod 33 is overlapped with the central axis of the impact top cover 32, the outer side of the liquid separation pipe 31 is sleeved with a first spring 35, the first spring 35 is located between the bottom wall of the impact top cover 32 and the top surface of the suspension bracket 17, the bottom of the liquid separation pipe 31 is provided with a first quick connector 37 communicated with the inside of the liquid separation pipe 31, the liquid injection pipe is provided with an electromagnetic valve, the pipe wall of the liquid separation pipe 31 is provided with an interlayer, the interlayer is provided with a heating wire 36, the side wall of the impact top cover 32 is provided with a liquid inlet pipe 34 communicated with the inside of the liquid separation pipe 31, the liquid inlet pipe 34 is communicated with the liquid outlet pipe 27, the impact top cover 32 is further provided with an auxiliary discharging assembly similar to the distributing device 20, the side wall of the liquid distributing pipe 31 is further provided with a temperature sensor, the detection end of the temperature sensor is located inside the liquid distributing pipe 31, liquid is quantitatively discharged through the distributing device 20, mixed liquid is guided into the liquid distributing pipe 31 through the liquid inlet pipe 34, the mixed liquid is heated to the synthetic temperature through the heating wire 36, and the electric push rod 33 drives the liquid distributing pipe 31 to inject liquid downwards.

Oscillating seat device 40 includes installation shell 41, the inside relative both sides of installation shell 41 all are provided with inner panel 43 and planking 42, inner panel 43 and planking 42 are connected through flexible guide arm, and the outside cover of flexible guide arm is equipped with second spring 44, the upper and lower both sides of the lateral wall of the relative installation shell 41 of planking 42 all are provided with the plunger hole, the downthehole fore-set 45 that is provided with of plunger, the one end of fore-set 45 extends to the installation shell 41 outside, the other end of fore-set 45 passes through boss swing joint with the lateral wall of planking 42, correspondingly, cylinder 11 is all installed to the upper and lower both sides of ring conveyor 12, and the mounting height in the output shaft of cylinder 11 equals respectively with the mounting height in plunger hole.

The synthesis assembly 50 comprises a synthesis pipe 51 and a base 55 arranged inside the synthesis pipe 51, wherein a pipe seat 52 is arranged at the top end of the synthesis pipe 51, a second quick connector 53 matched with the first quick connector 37 is arranged in the pipe seat 52, a one-way air valve communicated with the outer side of the synthesis pipe 51 is also arranged on the pipe seat 52, a sewage discharge pipe 56 communicated with the synthesis pipe 51 is arranged at the bottom of the synthesis pipe 51, a sewage suction connector is arranged on the sewage discharge pipe 56, and a synthesis column 54 is clamped on the base 55; the mixed solution after the temperature rise is injected into the synthesis tube 51 to synthesize nucleic acid, and the solution preparation synthesis is completed.

The synthesis tube 51 is a heat preservation tube with a vacuum interlayer arranged in the tube wall, so that the heat loss is reduced.

A feeding device is arranged on one side of the control cabinet 16 and comprises a shelf 13 fixedly mounted with the frame 10, a plurality of raw material tanks 14 for containing synthetic raw materials are arranged on the shelf 13, and the raw material tanks 14 are communicated with the liquid distribution pipe 15.

The electromagnetic valve, the flowmeter, the air cylinder 11, the ring conveyor 12 and other electrical elements are controlled by PLC programming, and the content which is not described in detail in the specification belongs to the prior art which is well known to the technical personnel in the field.

The working principle of the invention is as follows:

when the invention is used, the raw material tank 14 quantitatively conveys the synthetic raw materials into the liquid mixing pipe 22 through the liquid distribution pipe 15 and the control system, meanwhile, the bidirectional air pump pumps the air in the liquid mixing pipe 22 to the outside, the ultrasonic generator 24 sends ultrasonic vibration to the ultrasonic vibrating rod 26 to uniformly mix the synthetic raw materials, then the bidirectional air pump continuously pumps sterile air into the liquid mixing pipe 22 to discharge the mixed liquid into the liquid separating pipe 31 at a certain pressure, the electric heating wire 36 heats the mixed liquid to the synthesis temperature, the electric push rod 33 is started to drive the liquid separating pipe 31 to move downwards, the first joint and the second joint are conducted, the heated mixed solution is introduced into the synthesis pipe 51 for heat preservation reaction, the output end of the air cylinder 11 lifts the top column 45 in a reciprocating way, the outer plate 42 presses the second spring 44, and the inner plate 43 contacts the combining pipe 51, thereby driving the combining pipe 51 to oscillate and accelerating the combining.

In the description herein, references to the description of "one embodiment," "an example," "a specific example" or the like are intended to mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

The foregoing is merely exemplary and illustrative of the principles of the present invention and various modifications, additions and substitutions of the specific embodiments described herein may be made by those skilled in the art without departing from the principles of the present invention or exceeding the scope of the claims set forth herein.

Claims

1. An automatic liquid preparation synthesizer for medicinal nucleic acid comprises a rack (10), an annular conveyor (12) arranged in the middle of the rack (10) and a control cabinet (16) arranged at the top of the rack (10), and is characterized in that a batching device (20) is arranged in the control cabinet (16), a suspension bracket (17) is fixedly arranged below the control cabinet (16), a liquid injection device (30) is arranged on the suspension bracket (17), an oscillating seat device (40) is arranged on the annular conveyor (12), and a synthesis assembly (50) is arranged in the oscillating seat device (40);

the liquid injection device (30) comprises a liquid distribution pipe (31) and an electric push rod (33) arranged above the liquid distribution pipe (31), the liquid distribution pipe (31) penetrates through the suspension frame (17) and is slidably mounted with the suspension frame (17) through a sliding sleeve, a first quick joint (37) is arranged at the bottom of the liquid distribution pipe (31), and an electric heating wire (36) is arranged in the pipe wall of the liquid distribution pipe (31).

2. The automatic liquid-dispensing synthesizer for medicinal nucleic acid according to claim 1, wherein the top end of the liquid-separating tube (31) is provided with an impact cap (32), the outer side of the liquid-separating tube (31) is sleeved with a first spring (35), and the first spring (35) is located between the bottom wall of the impact cap (32) and the top surface of the suspension bracket (17).

3. The automatic liquid mixing synthesizer for the medicinal nucleic acid according to claim 1, wherein the mixing device (20) comprises a liquid mixing tube (22) and a tube frame (21) for fixing the liquid mixing tube (22), a plurality of raw liquid joints (23) are arranged on the side wall of the liquid mixing tube (22), a tube cover (25) is arranged at the top end of the liquid mixing tube (22), an ultrasonic generator (24) is arranged at the top of the tube cover (25), and the output end of the ultrasonic generator (24) is connected with an ultrasonic vibrating rod (26) extending to the inside of the liquid mixing tube (22).

4. The automatic liquid preparation synthesizer for medicinal nucleic acid according to any one of claims 2-3, wherein the impact top cover (32) and the tube cover (25) are provided with auxiliary discharging components, the auxiliary discharging components comprise pressure connectors respectively communicated with the liquid separating tube (31) and the liquid mixing tube (22), and the pressure connectors are communicated with a bidirectional air pump.

5. The automatic liquid preparation synthesizer for the medicinal nucleic acid according to claim 1, wherein the oscillating base device (40) comprises a mounting shell (41), an inner plate (43) and an outer plate (42) are arranged on two opposite sides inside the mounting shell (41), the inner plate (43) and the outer plate (42) are connected through a telescopic guide rod, a second spring (44) is sleeved outside the telescopic guide rod, plunger holes are arranged on the upper side and the lower side of the side wall of the mounting shell (41) opposite to the outer plate (42), a top pillar (45) is arranged in each plunger hole, one end of each top pillar (45) extends to the outside of the mounting shell (41), and the other end of each top pillar (45) is movably connected with the side wall of the outer plate (42) through a shaft joint.

6. The automatic liquid preparation synthesizer for medicinal nucleic acid according to claim 5, wherein the upper and lower sides of the ring conveyor (12) are provided with air cylinders (11), and the installation height of the output shaft of the air cylinder (11) is equal to the installation height of the plunger hole.

7. The automatic liquid preparation synthesizer for the medicinal nucleic acid as claimed in claim 1, wherein the synthesis assembly (50) comprises a synthesis tube (51) and a base (55) arranged inside the synthesis tube (51), a tube seat (52) is arranged at the top end of the synthesis tube (51), a second quick connector (53) is arranged in the tube seat (52), a one-way air valve is further arranged on the tube seat (52), a sewage discharge pipe (56) is arranged at the bottom of the synthesis tube (51), a sewage suction connector is arranged on the sewage discharge pipe (56), and a synthesis column (54) is clamped on the base (55).

8. The automatic liquid preparation synthesizer for medicinal nucleic acid according to claim 1, wherein a feeding device is further disposed on one side of the control cabinet (16), the feeding device comprises a rack (13) fixedly mounted with the frame (10), a plurality of raw liquid tanks (14) for holding synthetic raw materials are disposed on the rack (13), the raw liquid tanks (14) are communicated with the liquid distribution pipe (15), and the liquid distribution pipe (15) is communicated with the raw liquid joint (23).