CN214390174U - Continuous synthesis device for metformin hydrochloride - Google Patents
Continuous synthesis device for metformin hydrochloride Download PDFInfo
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- CN214390174U CN214390174U CN202122019655.1U CN202122019655U CN214390174U CN 214390174 U CN214390174 U CN 214390174U CN 202122019655 U CN202122019655 U CN 202122019655U CN 214390174 U CN214390174 U CN 214390174U
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Abstract
The utility model provides a continuous synthesis device for metformin hydrochloride. The continuous synthesis device of the metformin hydrochloride comprises: the device comprises a synthesis device body and a microwave device, wherein the synthesis device body comprises a reaction section and a condensation section which are sequentially communicated and arranged along the flowing direction of materials, the reaction section is provided with a feed inlet, the condensation section is provided with a discharge outlet, and the condensation section is used for cooling and crystallizing the materials; and the microwave device is arranged at the outer side of the reaction section. The adoption of the continuous synthesis device is beneficial to greatly reducing the impurity content in the product, improving the yield of the target product, reducing the process energy consumption, improving the environmental protection property and facilitating the popularization and application of the continuous process.
Description
Technical Field
The utility model relates to a metformin production field particularly, relates to a continuous synthesizer of metformin hydrochloride.
Background
The metformin tablet is preferably used for treating ineffective type 2 diabetes, especially obese type 2 diabetes, by simple diet control and physical exercise. The product can be used together with insulin to reduce insulin dosage and prevent hypoglycemia. Can be used together with sulfonylurea hypoglycemic agent, and has synergistic effect. The existing literature reports that the use of metformin in the fasting state can significantly inhibit tumor growth, and suggests that the PP2A-GSK3 beta-MCL-1 pathway may be a new target for tumor therapy. The hydrochloride is commonly used and is white crystal or crystalline powder; no bad smell. Is soluble in water, soluble in methanol, slightly soluble in ethanol, and insoluble in chloroform, acetonitrile or diethyl ether.
The traditional process for obtaining metformin hydrochloride is to dissolve cyclohexanol, dicyandiamide and dimethylamine hydrochloride at 160 ℃ in a traditional reaction kettle type reactor, and the reaction time is about 1.5h in the process that the system is from solid state to liquid state to solid state. The reaction product is purified in a certain amount of ethanol, so that higher purity and yield are achieved. However, the above process has the following disadvantages: the batch reaction can emit huge heat, which is very easy to cause kettle explosion; the feeding amount is large, and great potential safety hazards exist; the product can grow on the wall surface during crystallization and can be adhered to the surface and cannot fall off well; a plurality of kettles are needed for operation during production, and the occupied area is large; the reaction solvent can not be recycled, the discharge of three wastes is increased, and the cost is wasted; the reaction kettle is operated intermittently, so that the integral service cycle is long and the utilization rate is not high; the automation degree of the equipment is low, and the labor cost is high; slow dissolving time and low efficiency.
In order to overcome the above problems, the prior art reports a continuous synthetic system of metformin hydrochloride, which comprises: the continuous reaction device is provided with a reaction material communicating port and is used for continuously synthesizing the metformin hydrochloride product, and the reaction material communicating port is used for discharging the metformin hydrochloride product; the discharging unit is communicated with the reaction material communicating port; one-level discharge apparatus is provided with charge door, first material mouth and the first discharge opening of connecing, and first material mouth and reaction material intercommunication mouth are linked together through first pipeline of unloading, and the charge door is used for adding the synthetic raw materials of metformin hydrochloride product. The device can well improve the stability and the heat dissipation of the product, but the content of impurities in the product obtained by the continuous reaction is still more, and the yield of the product is not too high.
In order to solve the technical problems, a continuous synthesis system of metformin hydrochloride with less impurity content and low product yield is needed.
SUMMERY OF THE UTILITY MODEL
The main object of the utility model is to provide a to there are few and the low problem of product yield in the continuous synthesis system of current metformin hydrochloride in solution.
In order to achieve the above object, the present invention provides a continuous synthesis device for metformin hydrochloride, which is characterized in that the continuous synthesis device for metformin hydrochloride comprises: the device comprises a synthesis device body and a microwave device, wherein the synthesis device body comprises a reaction section and a condensation section which are sequentially communicated and arranged along the flowing direction of materials, the reaction section is provided with a feed inlet, the condensation section is provided with a discharge outlet, and the condensation section is used for cooling and crystallizing the materials; and the microwave device is arranged at the outer side of the reaction section.
Further, the continuous synthesis device for the metformin hydrochloride further comprises a stirring device, wherein the stirring device is arranged inside the synthesis device body and extends along the length direction of the synthesis device body.
Further, the stirring device includes: the stirring rod extends along the length direction of the synthesis device body; and the stirring blade is fixed on the stirring rod, and the minimum distance between the stirring blade and the inner wall of the synthesis device body is less than or equal to 3 mm.
Furthermore, the synthesis device body further comprises a hollow cavity, the hollow cavity is sleeved outside the condensation section, and the hollow cavity is provided with a refrigerant inlet and a refrigerant outlet.
Further, the inner wall of the hollow cavity is provided with a bulge.
Further, the shape of the protrusions is selected from spheres, cylinders or pyramids.
Further, the continuous synthesis device for the metformin hydrochloride comprises a solvent supply device, wherein the solvent supply device is provided with a solvent supply port, and the solvent supply port is communicated with the feed port.
Further, the synthesis apparatus body is selected from a tubular reactor or a stirring type reactor.
Use the technical scheme of the utility model, because microwave penetrability is strong, enable the system and reach the state of inside and outside heating almost simultaneously, form body heat source state, this heat conduction time in can shortening the conventional heating greatly, and make the interior outer heating of material even unanimous. Therefore, the microwave device can inhibit the generation of byproducts in the synthesis reaction device body and improve the conversion rate of the metformin hydrochloride. Meanwhile, the thermal inertia of microwave heating is small, the microwave instantaneously heats the system to raise the temperature, the energy consumption is low, and the method is economical and environment-friendly. Meanwhile, the power of the microwave can be adjusted at any time, so that the phenomenon of waste heat does not exist, and the requirements of automatic control and continuous production are greatly met. In addition, the synthesis reaction device body is divided into a reaction section and a condensation section, reaction products can be condensed and crystallized through the condensation section, and impurities are still remained in the solution. By adopting the synthesis reaction device body, the generated product can be automatically settled, the product purity is improved, the using amount of the solvent is effectively reduced, the three-waste treatment is reduced, and the process cost is saved. On the basis, the adoption of the continuous synthesis device is beneficial to greatly reducing the impurity content in the product, improving the yield of the target product, reducing the process energy consumption, improving the environmental protection property and facilitating the popularization and application of the continuous process.
Drawings
The accompanying drawings, which form a part of the present application, are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention and not to limit the invention. In the drawings:
fig. 1 is a schematic structural diagram illustrating a device body for synthesizing metformin hydrochloride according to an exemplary embodiment of the present invention;
fig. 2 shows a schematic structural diagram of a continuous synthesis apparatus for metformin hydrochloride according to an exemplary embodiment of the present invention.
Wherein the figures include the following reference numerals:
10. synthesizing a device body; 11. a reaction section; 12. a condensing section; 13. a hollow cavity; 101. a feed inlet; 102. a discharge outlet; 103. a refrigerant inlet; 104. a refrigerant outlet; 20. a microwave device; 30. a stirring device; 40. a solid feeding device; 50. a mixing device; 51. a second conveying device; 60. a solvent supply device; 61. a first delivery pump; 70. a product storage device; 71. and a third conveying device.
Detailed Description
It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict. The present invention will be described in detail with reference to examples.
As described in the background art, the existing continuous synthesis system of metformin hydrochloride has the problems of low impurity content and low product yield. In order to solve the above technical problems, the present application provides a continuous synthesis apparatus for metformin hydrochloride, as shown in fig. 1 and 2, comprising: a synthesis apparatus body 10, a microwave apparatus 20 and a cooling apparatus. Along the flow direction of the material, the synthesis device body 10 comprises a reaction section 11 and a condensation section 12 which are sequentially communicated, wherein the reaction section 11 is provided with a feeding hole 101, the condensation section 12 is provided with a discharging hole 102, and the condensation section 12 is used for cooling and crystallizing the material.
In the continuous synthesis apparatus, under the action of the microwave provided by the microwave apparatus 20, the reaction raw materials such as organic solvent, dicyandiamide and dimethylamine hydrochloride in the solvent method, the reaction raw materials such as dicyandiamide and dimethylamine hydrochloride in the melting method enter the synthesis apparatus body 10 from the feed inlet 101 for reaction, and the reaction product enters the cooling section and is cooled, so that the required metformin hydrochloride is obtained.
Because the microwave penetrability is strong, can make the system reach the state of inside and outside heating almost simultaneously, form the body heat source state, this heat conduction time in can shortening conventional heating greatly, and make the inside and outside heating of material even unanimous. The provision of the microwave device 20 can suppress the production of by-products in the synthesis reaction device body and improve the conversion rate of metformin hydrochloride. Meanwhile, the thermal inertia of microwave heating is small, the microwave instantaneously heats the system to raise the temperature, the energy consumption is low, and the method is economical and environment-friendly. Meanwhile, the power of the microwave can be adjusted at any time, so that the phenomenon of waste heat does not exist, and the requirements of automatic control and continuous production are greatly met. In addition, as shown in fig. 1, the above synthesis reaction apparatus body is divided into a reaction section 11 and a condensation section 12, and the reaction product can be condensed and crystallized by the condensation section 12 while the impurities remain in the solution. By adopting the synthesis reaction device body, the generated product can be automatically settled, the product purity is improved, the using amount of the solvent is effectively reduced, the three-waste treatment is reduced, and the process cost is saved. On the basis, the adoption of the continuous synthesis device is beneficial to greatly reducing the impurity content in the product, improving the yield of the target product, reducing the process energy consumption, improving the environmental protection property and facilitating the popularization and application of the continuous process.
In a preferred embodiment, as shown in fig. 1 and 2, the continuous synthesis device for metformin hydrochloride further comprises a stirring device 30, and the stirring device 30 is disposed inside the synthesis device body 10 and extends along the length direction of the synthesis device body 10. The reaction device with the stirring device 30 is selected to be beneficial to improving the mixing uniformity of the reaction raw materials, thereby being beneficial to further improving the conversion rate of the target product.
The stirring device 30 may be a structure commonly used in the art, and includes, for example, a stirring rod extending along the length direction of the synthesizing device body 10 and a stirring blade fixed to the stirring rod. The distance between the stirring blade and the inner wall of the synthesis apparatus body 10 affects the mixing uniformity of the reaction raw materials, and preferably, the minimum distance between the stirring blade and the inner wall of the synthesis apparatus body 10 is less than or equal to 3 mm. Compared with other ranges, limiting the minimum distance between the stirring blade and the inner wall of the synthesis device body 10 in the above range is beneficial to further improving the uniformity of the reaction system, reducing the crystallization rate of the target product, inhibiting the discharge port 102 from being blocked, and improving the yield of the target product.
The condensation section 12 described above may be condensed in a manner conventional in the art. In a preferred embodiment, as shown in fig. 1, the synthesis device body 10 further includes a hollow cavity 13, the hollow cavity 13 is disposed outside the condensation section 12, and the hollow cavity 13 is provided with a refrigerant inlet 103 and a refrigerant outlet 104. Through the arrangement of the hollow cavity 13 and the cooling by the flowing heat exchange of the refrigerant, crystals of the metformin hydrochloride can be precipitated under mild conditions, and the precipitation rate of impurities can be reduced, so that the purity of the metformin hydrochloride is further improved.
In order to further improve the heat exchange efficiency of the refrigerant, it is preferable that the inner wall of the hollow cavity 13 is provided with a protrusion. The inner wall is provided with the bulges, so that the turbulence degree of the refrigerant can be improved, the heat exchange efficiency of the refrigerant can be further improved, and the purity of the metformin hydrochloride can be further improved.
The projections may be of a combination of shapes as is common in the art. More preferably, the shape of the above-mentioned protrusions is selected from a sphere, a cylinder or a pyramid. Further preferably, the cross section of the hollow cavity is annular, and the maximum height of the protrusion is smaller than 1/2 of the radial width of the annular region, or the projections of the protrusions on the longitudinal section of the hollow cavity do not overlap. The arrangement mode can keep the refrigerant in the hollow cavity in a turbulent state on one hand, and can provide enough flowing space for the refrigerant on the other hand, thereby being beneficial to further improving the crystallization effect and the purity of the metformin hydrochloride.
Problems in the synthesis reaction apparatus body can be precisely controlled by providing a heat source using the microwave apparatus 20. In order to further adjust the reaction temperature thereof, it is preferable that the continuous synthesis apparatus for metformin hydrochloride comprises a solvent supply means provided with a solvent supply port disposed in communication with the feed port 101.
In a preferred embodiment, the synthesis apparatus body 10 includes, but is not limited to, a tubular reactor or a stirred reactor.
Example 1
Metformin hydrochloride was prepared using the apparatus shown in FIG. 2.
The preparation method comprises the following steps:
reaction raw materials (the molar ratio of dicyandiamide to dimethylamine hydrochloride is 1: 1.1) are added into a mixing device 50 through a solid feeding device 40, a solvent (the solvent is cyclohexanol, the volume ratio of the solvent to the volume of each mole of dicyandiamide is 2: 1) provided by a solvent supply device 60 is conveyed into the mixing device 50 through a first conveying pump 61, and the reaction raw materials and the solvent are mixed to obtain a mixed solution.
The mixed solution is conveyed by the second conveying device 51, is input into the reaction section 11 of the synthesis device body 10 through the feed inlet 101, and then is subjected to continuous reaction under the action of the microwave device 20 and the stirring device 30, wherein the reaction temperature is 150-165 ℃. The reacted material continuously enters the condensation section 12, and is crystallized under the cooling effect of a refrigerant (water, the temperature is 40 ℃) in the hollow cavity 13 to obtain crystals of the metformin hydrochloride, and the crystals are stored in the product storage device 70 through the third conveying device 71.
The yield of the crystal of the metformin hydrochloride is 82-87%, and the purity is 90-94%.
Example 2
The differences from example 1 are: the synthesis apparatus body 10 used is a tubular reactor and does not contain a stirring device.
The yield of the crystals of the metformin hydrochloride is 74-80%, and the purity is 84-87%.
Comparative example 1
The reaction raw materials were the same as in example 1, and the reaction process was carried out in a batch reaction in an autoclave.
The yield of the crystal of the metformin hydrochloride is 69-72%, and the purity is 78-82%.
Comparative example 2
The reaction raw materials are the same as in example 1, and the temperature of the condensation section 12 is controlled by a temperature control jacket.
The yield of the crystals of the metformin hydrochloride is 73-78%, and the purity is 77-83%.
From the above description, it can be seen that the above-mentioned embodiments of the present invention achieve the following technical effects: the adoption of the continuous synthesis device is beneficial to greatly reducing the impurity content in the product, improving the yield of the target product, reducing the process energy consumption, improving the environmental protection property and facilitating the popularization and application of the continuous process.
It is noted that the terms first, second and the like in the description and in the claims of the present application are used for distinguishing between similar elements and not necessarily for describing a particular sequential or chronological order. It is to be understood that the terms so used are interchangeable under appropriate circumstances such that the embodiments of the application described herein are, for example, capable of operation in sequences other than those described or illustrated herein.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (7)
1. A continuous synthetic device of metformin hydrochloride is characterized by comprising:
the device comprises a synthesis device body (10), wherein the synthesis device body (10) comprises a reaction section (11) and a condensation section (12) which are sequentially communicated with each other along the flowing direction of materials, the reaction section (11) is provided with a feeding hole (101), the condensation section (12) is provided with a discharging hole (102), and the condensation section (12) is used for cooling and crystallizing the materials passing through; and
a microwave device (20), wherein the microwave device (20) is arranged outside the reaction section (11); the continuous synthesis device for the metformin hydrochloride further comprises a stirring device (30), wherein the stirring device (30) is arranged inside the synthesis device body (10) and extends along the length direction of the synthesis device body (10).
2. The continuous synthesis plant of metformin hydrochloride according to claim 1, wherein said stirring means (30) comprises:
a stirring rod extending in a longitudinal direction of the synthesizing device body (10); and
the stirring blades are fixed on the stirring rod, and the minimum distance between each stirring blade and the inner wall of the synthesis device body (10) is less than or equal to 3 mm.
3. The continuous synthesis device of metformin hydrochloride according to claim 1, wherein the synthesis device body (10) further comprises a hollow cavity (13), the hollow cavity (13) is sleeved outside the condensation section (12), and the hollow cavity (13) is provided with a refrigerant inlet (103) and a refrigerant outlet (104).
4. The continuous synthesis apparatus of metformin hydrochloride according to claim 3, wherein the inner wall of said hollow cavity (13) is provided with a protrusion.
5. The continuous synthesis apparatus of metformin hydrochloride according to claim 4, wherein said protrusions have a shape selected from the group consisting of a sphere, a cylinder and a pyramid.
6. The device for the continuous synthesis of metformin hydrochloride according to any one of claims 1 to 5, wherein the device for the continuous synthesis of metformin hydrochloride comprises a solvent supply device provided with a solvent supply port, said solvent supply port being provided in communication with said feed port (101).
7. The continuous synthesis plant of metformin hydrochloride according to claim 1, wherein said synthesis plant body (10) is selected from a tubular reactor or a stirred reactor.
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| CN202122019655.1U CN214390174U (en) | 2021-08-26 | 2021-08-26 | Continuous synthesis device for metformin hydrochloride |
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| CN202122019655.1U CN214390174U (en) | 2021-08-26 | 2021-08-26 | Continuous synthesis device for metformin hydrochloride |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023147729A1 (en) * | 2022-02-07 | 2023-08-10 | 天津凯莱英医药科技发展有限公司 | Continuous synthesis system and method for metformin hydrochloride |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2023147729A1 (en) * | 2022-02-07 | 2023-08-10 | 天津凯莱英医药科技发展有限公司 | Continuous synthesis system and method for metformin hydrochloride |
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Effective date of registration: 20230412 Address after: 133700 No. 99, Hongda Road, Dunhua Economic Development Zone, Yanbian Korean Autonomous Prefecture, Jilin Province Patentee after: Kailaiying Pharmaceutical Chemistry (Jilin) Technology Co.,Ltd. Address before: No.71, 7th Street, Binhai New Area Economic and Technological Development Zone, Tianjin 300457 Patentee before: ASYMCHEM LIFE SCIENCE (TIANJIN) Co.,Ltd. |
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