A liquid phase synthesis apparatus

Abstract

This invention provides a liquid-phase synthesis apparatus, comprising: a liquid-phase synthesis vessel, wherein the liquid-phase synthesis vessel includes a synthesis vessel body, an upper baffle plate, a lower baffle plate, and an external heat exchanger. Compared with the prior art, this invention has the following beneficial effects: by adding a liquid-phase synthesis vessel and a vessel cover assembly, the vessel cover assembly is sealed and installed above the synthesis vessel body. The upper and lower stirring blades are driven by the stirring shaft to stir, and a convection structure is achieved. The liquid impacts the upper and lower baffle plates during stirring, forming turbulence, which makes the mixture form a complex flow structure. In the constant temperature control, the built-in upper and lower baffle plates and the external heat exchanger improve the temperature control effect, thereby improving the liquid-phase synthesis effect. By adding the synthesis vessel assembly, the feed conduit guides the raw material to the feed distribution pipe, and the raw material falls into different areas through the discharge hole during spiral conveying, thereby further improving the liquid-phase synthesis effect.

Description

Technical Field

[0001] This invention belongs to the field of synthesis technology of oral preparations of smegglutide, and specifically relates to a liquid-phase synthesis apparatus. Background Technology

[0002] Smegglutide oral formulation is a novel hypoglycemic agent based on a GLP-1 receptor agonist. It is used to treat type 2 diabetes and obesity-related diseases in adults by delaying gastric emptying, suppressing appetite, and promoting insulin secretion. Its molecular structure consists of a 31-amino acid polypeptide chain with an octadecanoic acid side chain modified at the 26th lysine residue. This unique structure endows it with long-acting pharmacokinetic properties, but also presents significant synthetic challenges. The preparation of smegglutide oral formulation involves both solid-phase and liquid-phase synthesis methods. While the traditional solid-phase synthesis method (SPPS) is widely used in peptide synthesis, it has revealed a series of inherent drawbacks in smegglutide production: it requires expensive resin carriers, generates large amounts of polymer waste, and is difficult to achieve continuous production, resulting in high production costs. In liquid-phase synthesis, multiple raw materials are introduced into the reactor to complete the mixing and synthesis. However, the commonly used reactor structure often has a large capacity, and the existing technology mostly uses a single stirrer or an irregularly shaped stirrer to complete the stirring. This stirring synthesis method has the problem of insufficient mixing, which cannot achieve efficient and high-quality preparation and use. Moreover, the constant temperature in the synthesis of smegglutide oral formulation will affect the quality of its finished product. The existing technology mostly uses an external heat exchanger to achieve constant temperature auxiliary control, which has the problem of delayed heat exchange in the central part of the reactor due to the large volume of the reactor structure.

[0003] In summary, we hope to propose a new structure to solve the aforementioned technical problems. Utility Model Content

[0004] In view of the shortcomings of the existing technology, the purpose of this utility model is to provide a liquid phase synthesis device to solve the problems mentioned in the background art.

[0005] This utility model is achieved through the following technical solution: a liquid phase synthesis device, comprising: a liquid phase synthesis vessel, wherein the liquid phase synthesis vessel includes a synthesis vessel body, an upper baffle plate, a lower baffle plate and an external heat exchanger, wherein a plurality of sets of circumferentially equally distributed upper baffle plates are fixedly connected to the upper inner side of the synthesis vessel body for mixing and stirring to form complex turbulence and improve the synthesis effect, wherein a plurality of sets of circumferentially equally distributed lower baffle plates are fixedly connected to the lower inner side of the synthesis vessel body, and an external heat exchanger is fixedly connected to the outer side of the synthesis vessel body;

[0006] A lid assembly is fixedly connected above the synthesis reactor body. The lid assembly includes a lid body, a stirring shaft, an upper stirring blade, and a lower stirring blade. A stirring shaft for driving the upper and lower stirring blades to rotate is fixedly connected below the lid body. An upper stirring blade is fixedly connected to the upper outer end of the stirring shaft, and a lower stirring blade is fixedly connected to the lower outer end of the stirring shaft.

[0007] In a preferred embodiment, the upper and lower baffles are arranged in an alternating structure inside the synthesis vessel body, and heat exchange chambers are provided on the inner sides of both the upper and lower baffles.

[0008] In a preferred embodiment, a heat exchange connecting pipe is fixedly connected between the adjacent upper and lower baffles, and several sets of heat exchange fins are fixedly connected to the outer sides of both the upper and lower baffles.

[0009] In a preferred embodiment, a heat exchange inlet pipe is fixedly connected to the left end of the upper baffle on the left side, and a heat exchange outlet pipe is fixedly connected to the left rear of the lower baffle at the left rear end. The inner surface of the synthesis vessel body is electrochemically polished and coated with a nano-zirconia coating to reduce the peptide adsorption rate. The heat exchange inlet pipe and the heat exchange outlet pipe form a circulating connection structure with the external heat exchanger, and the heat exchange medium is sequentially guided to several sets of upper and lower baffles, directly contacting the liquid phase inside the inner surface of the synthesis vessel body to achieve heat exchange.

[0010] In a preferred embodiment, an agitator motor is fixedly connected to the top of the vessel lid body and is fixedly connected to the agitator shaft via a coupling. Both the upper and lower agitator blades are conical spiral structures, and the upper agitator blade is an incremental conical spiral structure.

[0011] In a preferred embodiment, the lower agitator blade has a decreasing conical spiral structure and rotates in the opposite direction to the upper agitator blade. A set of sealing ring grooves is provided on the upper surface of the synthesis reactor body and the lower surface of the reactor cover body. A mating sealing ring is fixedly connected to the inner side of the upper sealing ring groove. The agitator shaft drives the upper and lower agitator blades, which are symmetrically arranged, to rotate. Under the action of the upper and lower agitator blades with conical structures, a convection vortex is formed, thereby improving the mixing effect of the raw materials.

[0012] In a preferred embodiment, two sets of symmetrically arranged connecting plates are fixedly connected to the upper outer end of the synthesis reactor body and the lower outer end of the reactor cover body. The upper and lower connecting plates are attached to each other and fixed by bolts, so that the sealing ring and the sealing ring groove at the lower end are sealed and fitted.

[0013] In a preferred embodiment, a set of feed conduits is fixedly connected to the upper surface of the reactor lid body, and a feed distribution pipe is fixedly connected below the feed conduits. The feed distribution pipe has a spiral structure and several sets of discharge holes are opened at the lower end of its outer side. The feed conduits guide the raw materials to the feed distribution pipes, and the raw materials fall into different areas through the discharge holes during spiral guidance, thereby further improving the liquid phase synthesis effect.

[0014] After adopting the above technical solution, the beneficial effects of this utility model are:

[0015] 1. By adding a liquid-phase synthesis reactor and reactor lid assembly, the reactor lid assembly is sealed and installed above the synthesis reactor body. The stirring shaft drives the upper and lower stirring blades to stir, realizing a convection structure. During stirring, the liquid impacts the upper and lower baffles to form turbulence, resulting in a complex flow structure. In the constant temperature control, the built-in upper and lower baffles and the external heat exchanger improve the temperature control effect, thereby improving the liquid-phase synthesis effect.

[0016] 2. By adding a synthesis reactor assembly, the feed conduit guides the raw materials to the feed distribution pipe, and the raw materials fall into different areas through the discharge hole during spiral conveying, thereby further improving the liquid phase synthesis effect. Attached Figure Description

[0017] To more clearly illustrate the technical solutions in the embodiments of this utility model or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this utility model. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0018] Figure 1 This is a schematic diagram of the overall structure of a liquid-phase synthesis device according to the present invention.

[0019] Figure 2 This is a schematic diagram of the structure of the liquid phase synthesis vessel in a liquid phase synthesis apparatus according to this utility model.

[0020] Figure 3 This is a partial cross-sectional schematic diagram of the liquid phase synthesis vessel in a liquid phase synthesis apparatus according to the present invention.

[0021] Figure 4 This is a schematic diagram of the upper structure of the reactor lid assembly in a liquid-phase synthesis apparatus according to the present invention.

[0022] Figure 5 This is a schematic diagram of the lower structure of the reactor lid assembly in a liquid-phase synthesis apparatus according to the present invention.

[0023] In the figure, 100-liquid phase synthesis vessel, 101-synthesis vessel body, 102-sealing ring groove, 103-connecting plate, 104-upper baffle plate, 105-lower baffle plate, 106-heat exchange fins, 107-heat exchange connecting pipe, 108-heat exchange cavity, 109-heat exchange inlet pipe, 110-external heat exchanger;

[0024] 200-Cabin lid assembly, 201-Cabin lid body, 202-Agitator motor, 203-Agitator shaft, 204-Upper agitator blade, 205-Lower agitator blade, 206-Feed conduit, 207-Feed distribution pipe, 208-Discharge hole, 209-Match sealing ring. Detailed Implementation

[0025] The technical solutions of the present utility model will be clearly and completely described below with reference to the accompanying drawings of the embodiments. Obviously, the described embodiments are only some embodiments of the present utility model, and not all embodiments. Based on the embodiments of the present utility model, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the protection scope of the present utility model.

[0026] Please see Figures 1-5 As the first embodiment of this utility model:

[0027] A liquid-phase synthesis apparatus includes: a liquid-phase synthesis vessel 100, wherein the liquid-phase synthesis vessel 100 includes a synthesis vessel body 101, an upper baffle 104, a lower baffle 105, and an external heat exchanger 110.

[0028] Several sets of upper baffles 104, which are circumferentially distributed, are fixedly connected to the upper inner side of the synthesis vessel body 101 for mixing and stirring to form complex turbulence and improve the synthesis effect. Several sets of lower baffles 105, which are circumferentially distributed, are fixedly connected to the lower inner side of the synthesis vessel body 101. An external heat exchanger 110 is fixedly connected to the outer side of the synthesis vessel body 101.

[0029] A lid assembly 200 is fixedly connected above the synthesis reactor body 101. The lid assembly 200 includes a lid body 201, a stirring shaft 203, an upper stirring blade 204, and a lower stirring blade 205. A stirring shaft 203 for driving the upper stirring blade 204 and the lower stirring blade 205 to rotate is fixedly connected below the lid body 201. The upper stirring blade 204 is fixedly connected to the upper outer end of the stirring shaft 203, and the lower stirring blade 205 is fixedly connected to the lower outer end of the stirring shaft 203.

[0030] The upper baffle 104 and the lower baffle 105 are arranged in an alternating structure inside the synthesis vessel body 101, and heat exchange chambers 108 are provided inside the upper baffle 104 and the lower baffle 105.

[0031] A heat exchange connecting pipe 107 is fixedly connected between the adjacent upper baffle 104 and lower baffle 105, and several sets of heat exchange fins 106 are fixedly connected to the outer side of both the upper baffle 104 and lower baffle 105.

[0032] A heat exchange inlet pipe 109 is fixedly connected to the left end of the upper baffle 104 on the left side, and a heat exchange outlet pipe is fixedly connected to the left rear of the lower baffle 105 at the left rear end. The inner surface of the synthesis vessel body 101 is electrochemically polished and coated with a nano-zirconia coating to reduce the peptide adsorption rate. The heat exchange inlet pipe 109 and the heat exchange outlet pipe form a circulating connection structure with the external heat exchanger, and the heat exchange medium is sequentially guided to several sets of upper baffles 104 and lower baffles 105, and heat exchange is achieved by direct contact with the liquid phase inside the synthesis vessel body 101.

[0033] An agitator motor 202 is fixedly connected to the top of the vessel lid body 201 and is fixedly connected to the agitator shaft 203 via a coupling. The upper agitator blade 204 and the lower agitator blade 205 are both conical spiral structures, and the upper agitator blade 204 is an incremental conical spiral structure.

[0034] The lower agitator 205 has a decreasing conical spiral structure and rotates in the opposite direction to the upper agitator 204. A set of sealing ring grooves 102 are provided on the upper surface of the synthesis vessel body 101 and the lower surface of the vessel cover body 201. A mating sealing ring 209 is fixedly connected to the inner side of the upper sealing ring groove 102. The agitator shaft 203 drives the upper agitator 204 and the lower agitator 205, which are symmetrically arranged, to rotate. Under the action of the conical upper agitator 204 and the lower agitator 205, a convection vortex is formed, thereby improving the mixing effect of the raw materials.

[0035] Two sets of symmetrically arranged connecting plates 103 are fixedly connected to the upper outer side of the synthesis reactor body 101 and the lower outer side of the reactor cover body 201. The upper and lower distributed connecting plates 103 are attached to each other and fixed by bolts, so that the mating sealing ring 209 is sealed and fitted with the sealing ring groove 102 at the lower end.

[0036] Specifically, the reactor lid assembly 200 is installed above the liquid phase synthesis reactor 100, so that the upper and lower distributed connecting plates 103 are attached to each other and fixed by bolts, and the sealing ring 209 is sealed and fitted with the sealing ring groove 102 at the lower end. The raw materials required for the synthesis of Smegglutide oral preparation are all introduced into the reactor body 101. The stirring motor 202 drives the stirring shaft 203 to rotate, and the stirring shaft 203 drives the upper stirring blade 204 and the lower stirring blade 205, which are symmetrically arranged, to rotate. Under the action of the upper stirring blade 204 and the lower stirring blade 205 with conical structure, a convection vortex is formed, thereby improving the mixing effect of raw materials. When the stirred liquid impacts the upper baffle plate 104 and the lower baffle plate 105, it is redirected and turbulence is formed, which further improves the mixing effect of raw materials.

[0037] Secondly, the heat exchange inlet pipe 109 and the heat exchange outlet pipe form a circulating connection with the external heat exchanger, and the heat exchange medium is sequentially guided to several sets of upper baffles 104 and lower baffles 105. The medium directly contacts the liquid phase inside the synthesis vessel body 101 to achieve heat exchange, and the external heat exchanger 110 is attached to the outer side of the synthesis vessel body 101 to assist in heat exchange and temperature control during synthesis. This improves the liquid phase synthesis effect of smegglutide oral preparations.

[0038] Please see Figure 1 and Figures 4-5 As a second embodiment of this utility model:

[0039] A set of feed conduits 206 are fixedly connected to the upper surface of the vessel lid body 201. A feed distribution pipe 207 is fixedly connected below the feed conduits 206. The feed distribution pipe 207 has a spiral structure and several sets of discharge holes 208 are opened at the lower end of its outer side. The feed conduits 206 guide the raw materials to the feed distribution pipe 207, and the raw materials fall into different areas through the discharge holes 208 during the spiral guidance.

[0040] Based on the first embodiment described above, furthermore, in the prior art, raw materials are often directly fed into a single area. In this invention, the raw materials required for the synthesis of smegglutide oral preparations are guided to the feed distribution pipe 207 through the feed conduit 206, and fall into different areas through the drop hole 208 during spiral conveying, thereby further improving the liquid phase synthesis effect.

[0041] The above description is only a preferred embodiment of the present utility model and is not intended to limit the present utility model. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present utility model should be included within the protection scope of the present utility model.

Claims

1. A liquid phase synthesis apparatus comprising: A liquid phase synthesis reactor (100) is characterized in that: the liquid phase synthesis reactor (100) includes a synthesis reactor body (101), an upper baffle plate (104), a lower baffle plate (105) and an external heat exchanger (110); The upper inner side of the synthesis vessel body (101) is fixedly connected to several sets of circumferentially distributed upper baffles (104) for mixing and stirring to form complex turbulence and improve the synthesis effect. The lower inner side of the synthesis vessel body (101) is fixedly connected to several sets of circumferentially distributed lower baffles (105). The outer side of the synthesis vessel body (101) is fixedly connected to an external heat exchanger (110). A lid assembly (200) is fixedly connected above the synthesis reactor body (101). The lid assembly (200) includes a lid body (201), a stirring shaft (203), an upper stirring blade (204), and a lower stirring blade (205). A stirring shaft (203) for driving the upper stirring blade (204) and the lower stirring blade (205) to rotate is fixedly connected below the lid body (201). An upper stirring blade (204) is fixedly connected to the upper outer end of the stirring shaft (203), and a lower stirring blade (205) is fixedly connected to the lower outer end of the stirring shaft (203).

2. A liquid phase synthesis apparatus as claimed in claim 1, characterized in that: The upper baffle (104) and the lower baffle (105) are arranged in an alternating structure inside the synthesis vessel body (101), and heat exchange chambers (108) are provided inside the upper baffle (104) and the lower baffle (105).

3. A liquid phase synthesis apparatus as claimed in claim 2, characterised in that: A heat exchange connecting pipe (107) is fixedly connected between the adjacent upper baffle (104) and lower baffle (105), and several sets of heat exchange fins (106) are fixedly connected to the outer side of the upper baffle (104) and lower baffle (105).

4. A liquid phase synthesis apparatus as claimed in claim 3, characterised in that: The upper baffle (104) on the left side is fixedly connected to a heat exchange inlet pipe (109) at its left end, and the lower baffle (105) at the left rear end is fixedly connected to a heat exchange outlet pipe at its left rear end. The inner surface of the synthesis vessel body (101) is electrochemically polished and coated with a nano-zirconia coating to reduce the peptide adsorption rate.

5. A liquid phase synthesis apparatus as claimed in claim 4, characterised in that: An agitator motor (202) is fixedly connected above the lid body (201) and is fixedly connected to the agitator shaft (203) via a coupling. The upper agitator (204) and the lower agitator (205) are both conical spiral structures, and the upper agitator (204) is an increasing conical spiral structure.

6. A liquid phase synthesis apparatus as claimed in claim 5, characterised in that: The lower stirring blade (205) has a decreasing conical spiral structure and rotates in the opposite direction to the upper stirring blade (204). A set of sealing ring grooves (102) are provided on the upper surface of the synthesis vessel body (101) and the lower surface of the vessel cover body (201). A mating sealing ring (209) is fixedly connected to the inner side of the upper sealing ring groove (102).

7. A liquid phase synthesis apparatus as claimed in claim 6, characterised in that: The upper outer end of the synthesis reactor body (101) and the lower outer end of the reactor cover body (201) are both fixedly connected with two sets of symmetrically arranged connecting plates (103). The upper and lower distributed connecting plates (103) are attached to each other and fixed by bolts, so that the mating sealing ring (209) is sealed and fitted with the sealing ring groove (102) at the lower end.

8. A liquid phase synthesis apparatus as claimed in claim 1, characterized in that: The kettle cover body (201) upper surface is still fixedly connected with a group of feeding guide pipes (206), the feeding guide pipes (206) below are fixedly connected with feeding distribution pipes (207), the feeding distribution pipes (207) are spiral structure and the outer side surface lower end is provided with a plurality of groups of material falling holes (208).

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