A laboratory crystallization device

Abstract

The present invention relates to the field of crystallization technology, and in particular to a laboratory crystallization device. It comprises a rotating drum, a barrel, a heating device and a rotating device; a seed crystal is arranged on the surface of the rotating drum, a feed liquid is contained inside the barrel, the rotating drum is placed above the feed liquid, so that the seed crystal layer on the surface of the rotating drum is immersed in the preset depth of the feed liquid surface, the feed liquid comprises an excess of solid material to be recrystallized, and the feed liquid dissolves the material to be recrystallized, the heating device is installed outside the barrel, and is used to heat the feed liquid to keep its temperature at a preset temperature, water with a temperature of a preset water temperature flows in the rotating drum, so that the temperature of the crystal layer on the rotating drum is the preset water temperature, and the rotating device is used to rotate the barrel. The present invention provides a laboratory crystallization device, which can obtain large-sized crystals.

Description

Technical Field

[0001] The invention relates to the technical field of crystallization, in particular to a laboratory crystallization device. Background Art

[0002] In the pharmaceutical field, the size of drug crystals has a certain impact on their dissolution rate, stability and bioavailability. In the laboratory research stage, it is of great significance to be able to crystallize drugs with larger crystals.

[0003] Therefore, in view of the above problems, there is an urgent need for a laboratory crystallization device that can obtain large-sized crystals. Summary of the invention

[0004] The present invention provides a laboratory crystallization device capable of obtaining large-sized crystals. The technical solution of the present invention is as follows:

[0005] A laboratory crystallization device comprises a rotating drum, a material barrel, a heating device and a rotating device;

[0006] The surface of the drum is provided with crystal seeds to form a crystal seed layer, the interior of the drum is filled with feed liquid, the drum is placed above the feed liquid, the crystal seed layer on the surface of the drum is immersed in the preset depth of the feed liquid surface, the feed liquid includes excess solid material to be recrystallized, the feed liquid dissolves the material to be recrystallized, the heating device is installed outside the drum, and is used to heat the feed liquid to keep its temperature at a preset temperature, water with a temperature of a preset water temperature flows in the drum, so that the temperature of the crystal layer on the drum is the preset water temperature, and the rotating device is used to rotate the drum; wherein the crystal layer is a crystal seed layer or a recrystallized layer obtained by recrystallization outside the crystal seed layer;

[0007] The crystallization method of a laboratory crystallization device comprises:

[0008] placing seed crystals on the surface of the drum to form a seed crystal layer;

[0009] Heating the liquid to a preset temperature and keeping it warm;

[0010] Placing the drum above the feed liquid so that the seed layer on the surface of the drum is immersed in the feed liquid to a preset depth;

[0011] Passing water of a preset water temperature into the drum so that the temperature of the drum is the preset water temperature; wherein the temperature of the preset water temperature is lower than the preset temperature;

[0012] The drum is rotated to allow the material to be recrystallized to crystallize on the seed crystal layer of the drum.

[0013] Preferably, the preset depth is 0-3 mm.

[0014] Preferably, the solid material to be recrystallized in the feed liquid is contained in a container with a filter screen, and the filter screen provided in the container is used to prevent the solid material to be recrystallized from escaping from the container.

[0015] Preferably, a spiral track is provided in the barrel, and the container is slidably lifted and lowered along the spiral track by a power device.

[0016] Preferably, the preset water temperature is 1-5°C lower than the preset temperature.

[0017] Preferably, the container is in the shape of an ellipsoid, and is provided with a plurality of through holes toward its center, the through holes are penetrated by through tubes whose apertures match the through holes and whose lengths are longer than the through holes, and both ends of the through tubes are respectively connected with curved panels matching the curvatures of the inner and outer walls of the container, and a filter is installed inside the through tubes.

[0018] Preferably, it also includes a position sensor and a feeding barrel, wherein the position sensor is used to measure the position of the liquid level in the barrel and the distance from the bottom of the crystal layer on the rotating drum to the liquid level;

[0019] Monitoring the liquid level of the feed liquid, and dynamically replenishing the feed liquid through a replenishing bucket according to the liquid level of the feed liquid, so that the liquid level of the feed liquid remains unchanged;

[0020] The depth of the outer surface of the crystal layer formed on the surface of the rotating drum immersed in the liquid surface of the feed liquid is monitored, and the height position of the rotating drum is adjusted according to the depth of the outer surface of the crystal layer formed on the surface of the rotating drum immersed in the liquid surface of the feed liquid, so that the depth of the outer surface of the crystal layer formed on the surface of the rotating drum immersed in the liquid surface of the feed liquid is maintained at a preset depth.

[0021] Preferably, the position sensor comprises a laser ranging sensor, a visual sensor and an acoustic wave sensor.

[0022] Preferably, the rotation speed of the rotating drum is 0.1-0.03 r / min.

[0023] Preferably, the drum is made of a heat-conducting material.

[0024] Compared with the prior art, the present invention has at least the following beneficial effects:

[0025] In this embodiment, the seed crystal is first set on the surface of the drum. Then the drum is placed above the feed liquid, so that the seed crystal layer covering the drum surface is in contact with the feed liquid surface. The feed liquid includes the material to be recrystallized that has been dissolved to saturation. When the seed crystal on the drum contacts the saturated feed liquid, it crystallizes to obtain large-sized crystals at the growth site provided by the seed crystal at the easy crystallization position of the solid-liquid interface. Before crystallization, the feed liquid needs to be heated to a preset temperature. After reaching the preset temperature, the feed liquid has a high solubility, and it is easy to drop in temperature when cooled, thereby precipitating crystals. In order to facilitate crystallization, water with a preset water temperature is introduced into the drum, and then the temperature of the drum is controlled to be the preset water temperature. The preset water temperature is lower than the preset temperature so that the saturated state in the feed liquid is destroyed, and the dissolved material to be recrystallized is precipitated under the promotion of the seed crystal. During the crystallization process, the drum needs to be rotated to prevent a certain position from being in contact with the feed liquid for a long time, resulting in a decrease in the temperature difference between the feed liquid and the crystals in contact with it, thereby inhibiting crystal growth. The rotating drum can not only prevent the crystals from being in contact with the liquid for a long time, but also grow crystals around the drum, so that a larger crystal surface can be obtained in a smaller space. In addition, the rotation of the drum can also make the liquid on the surface of the liquid flow. A certain fluidity can not only replenish the saturated or supersaturated liquid near the crystal layer, but also provide a certain vibration to promote crystallization. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0027] Figure 1 It is a schematic structural diagram of a laboratory crystallization device provided in an embodiment of the present invention.

[0028] Figure 2 It is a schematic diagram of the structure of a container in a laboratory crystallization device provided by an embodiment of the present invention.

[0029] In the figure:

[0030] 1- Rotating drum;

[0031] 2-barrel;

[0032] 3-Container;

[0033] 31-through-tube;

[0034] 32- curved panel;

[0035] 4- Heating device;

[0036] 5-Refilling barrel;

[0037] 6- Rotating device;

[0038] 7- Position sensor. DETAILED DESCRIPTION

[0039] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0040] like Figure 1 As shown, an embodiment of the present invention provides a laboratory crystallization device, including a rotating drum 1, a material barrel 2, a heating device 4 and a rotating device 6;

[0041] Seeds are arranged on the surface of the drum 1 to form a seed layer, and liquid feed is contained in the drum 2. The drum 1 is placed above the liquid feed so that the seed layer on the surface of the drum 1 is immersed in the liquid feed to a preset depth. The liquid feed includes an excess of solid material to be recrystallized so that the liquid feed dissolves the material to be recrystallized. The heating device 4 is installed on the outside of the drum 2 to heat the liquid feed to keep its temperature at a preset temperature. Water at a preset water temperature flows in the drum 1 so that the temperature of the crystal layer on the drum 1 is the preset water temperature. The rotating device 6 is used to rotate the drum 1; wherein the crystal layer is a seed layer or a recrystallized layer obtained by recrystallization outside the seed layer.

[0042] In this embodiment, the seed crystal is first set on the surface of the drum 1. Specifically, it can be glued to the surface of the drum 1 or pressed on the surface of the drum 1. Then the drum 1 is placed above the feed liquid, so that the seed crystal layer covering the surface of the drum 1 is immersed in the preset depth of the feed liquid surface. The feed liquid includes the material to be recrystallized that has been dissolved to saturation. When the seed crystal on the drum 1 contacts the saturated feed liquid, it crystallizes to obtain large-sized crystals at the growth site provided by the seed crystal at the easy crystallization part of the solid-liquid interface. Before crystallization, the feed liquid needs to be heated to a preset temperature. After reaching the preset temperature, the feed liquid has a high solubility, and it is easy to drop in temperature when cooled, thereby precipitating crystals. In order to facilitate crystallization, water at a preset water temperature is introduced into the drum 1, and then the temperature of the drum 1 is controlled to be the preset water temperature. The preset water temperature is lower than the preset temperature so that the saturated state in the feed liquid is destroyed, and the dissolved material to be recrystallized is precipitated under the promotion of the seed crystal. The water at the preset water temperature can be recycled through a circulation pipeline. During the crystallization process, it is necessary to rotate the drum 1 to prevent a certain position from being in contact with the feed liquid for a long time, which will reduce the temperature difference between the feed liquid and the crystals in contact with it and inhibit the growth of crystals. The rotating drum 1 can not only prevent the crystals from being in contact with the feed liquid for a long time, but also grow crystals all around the drum 1, so that a larger crystallization surface can be obtained in a smaller space. In addition, the rotation of the drum 1 can also make the liquid on the surface of the feed liquid flow. A certain fluidity can not only replenish the saturated or supersaturated feed liquid near the crystal layer, but also provide a certain vibration to promote crystal crystallization. It should be noted that whether it is promoting liquid flow or a certain liquid vibration, it needs to be kept in a lower range, otherwise, the crystallization environment is too unstable and the resulting crystal size is small.

[0043] In summary, the crystallization method of the above-mentioned laboratory crystallization device includes: setting seeds on the surface of the drum 1 to form a seed layer; heating the feed liquid to a preset temperature and keeping it warm; placing the drum 1 above the feed liquid so that the seed layer on the surface of the drum 1 is immersed in the feed liquid to a preset depth; passing water of a preset water temperature into the drum 1 so that the temperature of the drum 1 is the preset water temperature; wherein the temperature of the preset water temperature is lower than the preset temperature; rotating the drum 1 so that the material to be recrystallized crystallizes on the seed layer of the drum 1.

[0044] It should be noted that the rotation speed of the drum 1 is relatively slow, and the vibration it provides is extremely small, which is conducive to crystallization but will not cause large-scale disturbance to the liquid surface.

[0045] In this embodiment, the drum 1 can be a polygonal prism composed of multiple planes, or can be a cylindrical shape.

[0046] In some embodiments of the present invention, the preset depth is 0-3 mm.

[0047] In this embodiment, the optimal depth of the seed layer or the recrystallized crystal layer immersed in the liquid surface is 0 to 3 mm. If it is too deep, the temperature difference will be too small, the hydraulic pressure will be too large, and the crystal quality will be reduced.

[0048] It should be noted that the rotation speed of the drum 1 is relatively slow. In the process of its bottom part slowly rotating away from the liquid surface, due to the surface tension of the liquid surface, the part of the drum 1 that has just left the liquid surface will pull the liquid surface in contact with it to a certain height. At this height, the seed crystal can contact the liquid and has sufficient material basis to form recrystallized crystals. At the same time, at the force balance between the rising liquid level and the gravity of the liquid, the force is very weak and approaches zero, which will not affect the precipitation of the recrystallized crystals, allowing the crystals to fully crystallize and obtain larger crystals. If the drum 1 penetrates deeper below the liquid surface, the hydraulic pressure will be larger, which greatly affects the size of the recrystallized crystals.

[0049] In some embodiments of the present invention, the solid material to be recrystallized in the liquid feed is contained in a container 3 with a filter screen, and the filter screen provided in the container 3 is used to prevent the solid material to be recrystallized from escaping from the container 3 .

[0050] In this embodiment, the solid material to be recrystallized contained in the container 3 can be quickly dissolved in the liquid feed after part of the dissolved material is crystallized, thereby maintaining the saturation state of the material in the liquid feed; at the same time, it can prevent the solid material particles from flowing into the liquid feed, and then flowing onto the seed crystal and covering the seed crystal, resulting in the inability to obtain uniform, high-quality large crystals.

[0051] In some embodiments of the present invention, a spiral track is provided in the barrel 2, and the container 3 is slid and lifted along the spiral track by a power device.

[0052] In order to make the concentration of the dissolved material in the liquid uniform, the container 3 containing the solid material needs to be moved. It should be noted that a stirrer cannot be used for stirring. If a stirrer is used, although the material concentration can be made uniform, the liquid level cannot be guaranteed to be stable. If the liquid level oscillates, it will affect the crystallization environment at the drum 1 and large crystals cannot be obtained. In this embodiment, the power device can be a servo motor, which controls the container 3 to slowly and uniformly spiral up and down through the servo motor, and uses the spiral track to slowly drive the solute to move at different positions of the liquid, so that the material in the container 3 is directly dissolved at different positions, which can not only ensure the stability of the liquid level, but also make the overall solute content of the liquid more uniform.

[0053] In some embodiments of the present invention, the preset water temperature is 1-5°C lower than the preset temperature.

[0054] In this embodiment, the preset water temperature is 1-5°C lower than the preset temperature, and the temperature difference should not be too large. If the temperature difference is greater than the above range, the crystallization speed will be too fast and large crystals cannot be grown.

[0055] In some embodiments of the present invention, Figure 2As shown, the container 3 is an ellipsoid, and a plurality of through holes are opened toward the center of the container 3. The through holes are penetrated by through tubes 31 whose diameters match the through holes and whose lengths are longer than the through holes. The two ends of the through tubes 31 are respectively connected with curved panels 32 matching the curvatures of the inner and outer walls of the container 3, and a filter is installed inside the through tubes 31.

[0056] Since it is not possible to cause a large fluctuation in the state of the liquid surface, an ellipsoidal container with a pointed head and a smooth external curved surface is selected to ensure movement without causing a large disturbance to the liquid.

[0057] In this embodiment, the container 3 can be composed of a whole metal filter screen, but in order to prevent a large disturbance to the liquid surface, the container 3 still needs to be controlled to have a reasonable moving speed. Therefore, the dissolution rate of the solid recrystallized material in the container 3 will be affected to a certain extent. In order to solve this problem, a plurality of through-tubes 31 inclined toward the center of the container 3 are designed. During the forward process of the through-tube 31 in the forward direction, the curved plate 32 at the outer end will push the through-tube 31 into the container 3 under the action of the liquid. The curved plate 32 fits with the tip of the container 3, which will not affect the liquid separation function of the tip of the forward end. At the same time, the liquid flowing into the container 3 through the through-tube 31 has a faster flow rate, forming a fast flow rate in the container 3, accelerating dissolution, and small disturbance outside the container 3. The liquid in the container 3 flows out from the through-tube 31 at the rear end of the container 3, and the liquid pushes the curved plate 32 located inside the container 3 of the through-tube 31, so that the curved plate 32 is attached to the inner wall of the container 3. The through-tube 31 is mainly located outside the container 3, and the liquid dissolving the solute inside the container 3 is discharged from the through-tube 31 to the outside of the container 3. Since the through-tube 31 extends out of the container 3, the curved plate 32 outside the through-tube 31 partially disperses the liquid in the tail area of ​​the container 3, so that the liquid with solute discharged from the through-tube 31 is dispersed in multiple directions, achieving a rapid dispersion effect.

[0058] In some embodiments of the present invention, multiple heating devices 4 are arranged in the vertical direction around the barrel 2, and multiple temperature sensors are installed at different depths in the barrel 2. The power of each heating device 4 is dynamically adjusted according to the temperature of the temperature sensor to keep the temperature of the liquid at a preset temperature.

[0059] In this embodiment, temperature stability is the basis for growing large crystals. In order to stabilize the temperature of the slurry, multiple heating devices 4 are installed at different positions of the slurry, and multiple temperature sensors are installed in the slurry. Through the cooperation of the heating devices 4 and the temperature sensors, the temperature of the slurry reaches a dynamic balance and is always maintained at a preset temperature.

[0060] In some embodiments of the present invention, a position sensor 7 and a feeding barrel 5 are also included. The position sensor 7 is used to measure the position of the liquid level in the barrel 2 and to measure the distance from the bottom of the crystal layer on the rotating drum 1 to the liquid level.

[0061] Monitor the liquid level of the feed liquid, and dynamically replenish the feed liquid through the feed replenishment barrel 5 according to the liquid level of the feed liquid, so that the liquid level of the feed liquid remains unchanged;

[0062] The depth of the outer surface of the crystal layer formed on the surface of the rotating drum 1 immersed in the liquid surface is monitored, and the height position of the rotating drum 1 is adjusted according to the depth of the outer surface of the crystal layer formed on the surface of the rotating drum 1 immersed in the liquid surface of the feed liquid, so that the depth of the outer surface of the crystal layer formed on the surface of the rotating drum 1 immersed in the liquid surface of the feed liquid is maintained at a preset depth.

[0063] In some embodiments of the present invention, the position sensor 7 includes a laser ranging sensor, a visual sensor, and an acoustic wave sensor.

[0064] In this embodiment, as crystals in the liquid are precipitated and solid materials are dissolved, the volume of the liquid will change, which will cause the liquid level to change. Therefore, it is necessary to monitor the liquid level. In addition, as crystals continue to precipitate on the surface of the drum 1, the thickness of the crystal layer on the drum 1 will also change. Therefore, in order to ensure the immersion depth, the immersion depth of the crystal layer outside the drum 1 must also be monitored. Specifically, a laser ranging sensor can be used. By setting multiple laser ranging sensors at the bottom of the liquid, the laser is reflected when it is incident on the liquid surface. The liquid level can be obtained by the time difference between the emission and reception of the laser. Similarly, the height position of the crystal layer can also be obtained. Of course, other sensors that can measure position can also be selected, such as visual sensors and acoustic sensors.

[0065] In some embodiments of the present invention, the rotation speed of the rotating drum 1 is 0.1-0.03 r / min.

[0066] In this embodiment, rotating the drum 1 at the above rotation speed can not only slightly stir the liquid flow, but also keep the liquid surface calm and leave sufficient time and space for crystallization.

[0067] In some embodiments of the present invention, the drum 1 is made of a heat-conducting material, which can keep the temperature of the drum 1 consistent with the temperature of the water passing through it in a timely manner.

[0068] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A laboratory crystallization device, characterized in that: It comprises a rotating drum (1), a material drum (2), a heating device (4) and a rotating device (6); The surface of the drum (1) is provided with crystal seeds to form a crystal seed layer. The drum (2) is filled with liquid feed. The drum (1) is placed above the liquid feed so that the crystal seed layer on the surface of the drum (1) is immersed in the liquid feed to a preset depth. The liquid feed includes an excess of solid material to be recrystallized so that the liquid feed dissolves the material to be recrystallized. The heating device (4) is installed outside the drum (2) and is used to heat the liquid feed to keep its temperature at a preset temperature. Water at a preset water temperature flows through the drum (1) so that the temperature of the crystal layer on the drum (1) is the preset water temperature. The rotating device (6) is used to rotate the drum (1); wherein the crystal layer is a crystal seed layer or a recrystallized layer obtained by recrystallization outside the crystal seed layer. The crystallization method of the laboratory crystallization device comprises: Placing seed crystals on the surface of a rotating drum (1) to form a seed crystal layer; Heating the liquid to a preset temperature and keeping it warm; The rotating drum (1) is placed above the feed liquid, so that the seed layer on the surface of the rotating drum (1) is immersed in the feed liquid to a preset depth; Water of a preset water temperature is introduced into the rotating drum (1) so that the temperature of the rotating drum (1) is the preset water temperature; wherein the temperature of the preset water temperature is lower than the preset temperature; Rotating the drum (1) so that the material to be recrystallized crystallizes on the seed layer of the drum (1); The solid material to be recrystallized in the liquid is placed in a container (3) with a filter screen, and the filter screen provided in the container (3) is used to prevent the solid material to be recrystallized from escaping from the container (3); A spiral track is provided in the barrel (2), and the container (3) is slidably moved up and down along the spiral track by a power device; The container (3) is in the shape of an ellipsoid, and is provided with a plurality of through holes oriented toward the center thereof, the through holes are penetrated by through tubes (31) having a diameter matching the through holes and a length longer than the through holes, the two ends of the through tubes (31) are respectively connected to curved panels (32) matching the curvature of the inner wall and the outer wall of the container (3), and a filter is installed inside the through tubes (31).

2. A laboratory crystallization device according to claim 1, characterized in that: The preset depth is 0-3 mm, wherein the preset depth does not include a value of 0.

3. A laboratory crystallization device according to claim 1, characterized in that: The preset water temperature is 1-5°C lower than the preset temperature.

4. A laboratory crystallization device according to claim 1, characterized in that: It also includes a position sensor (7) and a feed barrel (5), wherein the position sensor (7) is used to measure the position of the liquid level in the barrel (2) and to measure the distance from the bottom of the upper crystal layer of the rotating barrel (1) to the liquid level; Monitoring the liquid level of the feed liquid, and dynamically replenishing the feed liquid through a replenishing bucket (5) according to the liquid level of the feed liquid, so that the liquid level of the feed liquid remains unchanged; The depth of the outer surface of the crystal layer formed on the surface of the rotating drum (1) immersed in the liquid surface of the feed liquid is monitored, and the height position of the rotating drum (1) is adjusted according to the depth of the outer surface of the crystal layer formed on the surface of the rotating drum (1) immersed in the liquid surface of the feed liquid, so that the depth of the outer surface of the crystal layer formed on the surface of the rotating drum (1) immersed in the liquid surface of the feed liquid is maintained at a preset depth.

5. A laboratory crystallization device according to claim 4, characterized in that: The position sensor (7) comprises a laser distance measuring sensor, a visual sensor and an acoustic wave sensor.

6. A laboratory crystallization device according to claim 1, characterized in that: The rotating drum (1) is rotated at a speed of 0.1-0.03 r / min.

7. A laboratory crystallization device according to claim 1, characterized in that: The rotating drum (1) is made of a heat-conducting material.

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