A tubular crystallizer and a crystallization method of biotin

Abstract

The application discloses a tubular crystallizer and a crystallization method of biotin. The tubular crystallizer comprises straight tubes and a bend pipe, each of the straight tubes has an upper end and a lower end, and the bend pipe connects the lower end of one straight tube with the upper end of another straight tube; the straight tubes comprise a first straight tube and a second straight tube, the upper end of the first straight tube is provided with a feed inlet, the first straight tube has a nucleation section and a growth section, and the lower end of the second straight tube is provided with a liquid outlet; the tubular crystallizer further comprises cooling jackets arranged on the straight tubes, the cooling jackets are provided with cooling liquid inlets and cooling liquid outlets, the cooling liquid inlets are close to the lower ends of the second straight tubes, and the cooling liquid outlets are close to the upper ends of the first straight tubes; and the tubular crystallizer further comprises a first temperature sensor for detecting the temperature of a solution in the lower end of the nucleation section. The tubular crystallizer can realize continuous production, reduce the floor area and reduce or even avoid the scaling of the wall.

Description

Technical Field

[0001] This invention relates to a tubular crystallizer and a method for crystallizing biotin. Background Technology

[0002] Currently, most biotin crystallization processes employ batch crystallization in a batch reactor. For products with large production capacities, batch crystallization processes require large crystallization reactors and numerous units, occupying significant space; manual operation is required in multiple batches, leading to high labor intensity; and batch reproducibility issues result in unstable product quality control. Furthermore, for cooling crystallization, scaling of the crystals onto the reactor walls frequently occurs, necessitating additional scaling cleaning procedures, increasing workload, and impacting production capacity. Summary of the Invention

[0003] To address the aforementioned problems, one objective of this invention is to provide a tubular crystallizer that enables continuous production, reduces floor space, and minimizes or even eliminates scaling on the vessel walls.

[0004] Another objective of this invention is to provide a method for crystallizing biotin that has a high yield, good crystal quality, and low energy consumption.

[0005] The first aspect of the present invention provides a tubular crystallizer, comprising a plurality of vertically arranged straight tubes and a plurality of bent tubes connected together, each of the straight tubes having an upper end and a lower end, and the bent tubes connecting the lower end of one straight tube to the upper end of another adjacent straight tube.

[0006] The plurality of straight tubes include a first straight tube and a second straight tube. The upper end of the first straight tube is provided with a feed inlet. The first straight tube has a nucleation section and a growth section. The lower end of the second straight tube is provided with a liquid outlet.

[0007] The tubular crystallizer further includes a cooling jacket disposed on the straight tube, the cooling jacket having a coolant inlet and a coolant outlet, the coolant inlet being close to the lower end of the second straight tube, and the coolant outlet being close to the upper end of the first straight tube;

[0008] The tubular crystallizer also includes a first temperature sensor for detecting the temperature of the solution in the lower end of the nucleation section, and a stirrer is provided in the nucleation section.

[0009] Preferably, the agitator is a wall-scraping agitator.

[0010] Preferably, the cooling jacket includes a first cooling jacket disposed on the nucleation section of the first straight pipe, the coolant outlet is disposed at the upper end of the first cooling jacket, and a first cooling inlet is disposed at the lower end of the first cooling jacket.

[0011] More preferably, the cooling jacket further includes a second cooling jacket disposed on the growth section of the first straight pipe and a third cooling jacket disposed on the second straight pipe. The upper end of the second cooling jacket is provided with a second cooling outlet and the lower end is provided with a second cooling inlet. The upper end of the third cooling jacket is provided with a third cooling outlet, and the coolant inlet is disposed at the lower end of the third cooling jacket.

[0012] More preferably, the bend is provided with a heat insulation layer.

[0013] Furthermore, the second cooling outlet is connected to the first cooling inlet, and the third cooling outlet is connected to the second cooling inlet.

[0014] Preferably, the tubular crystallizer further includes a disturbance device for agitating the liquid material within the straight tube and / or the curved tube.

[0015] More preferably, the disturbance device includes a reciprocating pump.

[0016] More preferably, the tubular crystallizer further includes a crystal grower, the crystal grower and the liquid outlet are connected by a pipeline, and the disturbance device is disposed on the second straight pipe or the pipeline.

[0017] Preferably, the bend is an arc-shaped bend. More preferably, the arc of the bend is a minor arc. Even more preferably, the bend and the straight pipe transition smoothly. That is, the middle of the bend arches towards the side farther from the straight pipe; for example, if the bend connects to the left side of two straight pipes, the middle of the bend arches to the left. Thus, the connection between the straight pipe and the bend forms a fluid passage for the crystallizing liquid, and this fluid passage does not abruptly change at the connection point of the straight pipe and the bend.

[0018] Preferably, the inner diameter of the bend is equal to the inner diameter of the straight pipe, and the radius of curvature of the bend is three times or more the inner diameter of the straight pipe.

[0019] More preferably, the centerline of each straight pipe and the centerline of each bend are in the same vertical plane, and the radius of curvature of the bend is 3 to 8 times the inner diameter.

[0020] Preferably, the angle between the straight pipe and the horizontal plane is 10 to 45 degrees. More preferably, the angle between each straight pipe and the horizontal plane is 15 to 30 degrees.

[0021] Preferably, the length of the straight pipe is 1 to 12 m, the inner diameter of the straight pipe is 20 to 200 mm, the outer diameter of the straight pipe is 25 to 219 mm, and the outer diameter of the cooling jacket is 45 to 273 mm.

[0022] Preferably, the inner walls of the straight pipe and the bent pipe are mirror-polished and have a roughness of less than 0.2. More preferably, the straight pipe and the bent pipe are stainless steel pipes, and the inner walls of the pipes are mirror-polished; the stainless steel pipes are further 304 stainless steel pipes. Optionally, the inner walls of the straight pipe and the bent pipe are provided with enamel glass bushings; the straight pipe and the bent pipe are further S30408 ​​stainless steel pipes.

[0023] Preferably, the tubular crystallizer further includes a scraper-type agitator disposed at the feed inlet.

[0024] Preferably, the bend is provided with a heat insulation layer.

[0025] In a specific and preferred embodiment, the lower end of the first straight pipe is connected to the upper end of the second straight pipe via a bend. A second temperature sensor is provided at the feed inlet, a third temperature sensor is provided at the bend, and a fourth temperature sensor is provided at the liquid outlet. A wall-scraping agitator is provided in the nucleation section. The liquid outlet is connected to the crystal grower. A reciprocating pump is provided on the second straight pipe. A first flow meter is also provided at the liquid outlet, and a second flow meter is also provided at the coolant outlet.

[0026] A second aspect of the present invention provides a method for crystallizing biotin, employing the aforementioned tubular crystallizer. The crystallization method includes the following steps: introducing a biotin crystallizing solution into the straight pipe through the feed inlet; introducing a coolant into the cooling jacket through the coolant inlet; the flow direction of the biotin crystallizing solution and the flow direction of the coolant being opposite; controlling the inlet flow rate of the biotin crystallizing solution and the outlet flow rate of the coolant to cause the concentration and temperature of the biotin crystallizing solution to decrease according to a set gradient; wherein, a pulse quantity of 0.1% to 1% of the total fluid volume within the tubular crystallizer is applied to the solution in the second straight pipe by a reciprocating pump. The pulse quantity refers to the product of the pulse frequency of the reciprocating pump and the cross-sectional area of ​​the plunger.

[0027] Preferably, the biotin mass fraction in the biotin crystallization solution is 0.8-1.1%, the feed temperature is 88-100℃, the discharge flow rate from the liquid outlet is 3-6 L / h, and the total residence time in the straight pipe and the curved pipe is 0.4-2 h.

[0028] Preferably, the feed temperature of the coolant at the coolant inlet is 18-28°C, and the flow rate at the coolant outlet is 3-6 L / h, with the flow rate of the coolant adjusted according to the temperature value detected by the first temperature sensor.

[0029] The present invention adopts the above solution, which has the following advantages compared with the prior art:

[0030] The tubular crystallizer of this invention employs a combination of connected inclined straight and curved pipes. An agitator is installed in the nucleation section of the first straight pipe, while no agitator is installed in other sections. Utilizing the characteristics of plug flow, the crystallization liquid moves slowly within the straight and curved pipes, preventing back-mixing and breakage within the pipes. Simultaneously, a cooling liquid removes heat from the crystallization liquid within the pipes at a set cooling rate, causing the concentration and temperature of the crystallization liquid to decrease synchronously in a gradient until the crystallization endpoint is reached. This avoids prolonged crystallization time, enabling continuous crystallization and achieving advantages such as high yield, low energy consumption, low mother liquor, good product quality, high automation, small equipment footprint, and fewer operators. Furthermore, this tubular crystallizer allows for cleaning between the crystals and the pipe wall, reducing or even preventing scaling. Attached Figure Description

[0031] To more clearly illustrate the technical solution of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0032] Figure 1 This is a schematic diagram of a tubular crystallizer according to an embodiment of the present invention.

[0033] Figure 2 This is a microscopic image of the liquid material after discharge in Example 1.

[0034] Figure 3 This is a microscopic image of the liquid material after discharge in Example 3.

[0035] Figure 4 This is a microscopic image of the liquid material after discharge from Comparative Example 1.

[0036] Figure label:

[0037] 1. High-temperature solution tank; 2. Tubular reactor;

[0038] 21. First straight pipe; 211. Feed inlet; 212. Nucleation section; 213. Growth section; 22. Bend; 23. Second straight pipe; 231. Liquid outlet; 24a. First temperature sensor; 24b. Second temperature sensor; 24c. Third temperature sensor; 24d. Fourth temperature sensor; 24e. Fifth temperature sensor; 24f. Sixth temperature sensor; 25a. First flow meter; 25b. Second flow meter; 26. Scraper-type agitator; 27. Crystal grower; 271. Piping; 272. Discharge valve; 28. Reciprocating pump;

[0039] 20a, First cooling jacket; 20b, Second cooling jacket; 20c, Third cooling jacket; 201, Coolant outlet; 202, First cooling inlet; 203, Second cooling outlet; 204, Second cooling inlet; 205, Third cooling outlet; 206, Coolant inlet. Detailed Implementation

[0040] The preferred embodiments of the present invention will now be described in detail with reference to the accompanying drawings, so that the advantages and features of the present invention can be more readily understood by those skilled in the art. It should be noted that the description of these embodiments is for the purpose of aiding understanding the present invention, but does not constitute a limitation thereof.

[0041] Reference Figure 1 As shown, the tubular crystallizer 2 includes several straight pipes arranged vertically and several bent pipes 22. Each straight pipe has an upper end and a lower end, and the bent pipe 22 connects the lower end of one straight pipe to the upper end of an adjacent straight pipe. The straight pipes include a first straight pipe 21 and a second straight pipe 23. The upper end of the first straight pipe 21 has a feed inlet 211 and a nucleation section 212 and a growth section 213. A wall-scraping agitator 26 is installed in the nucleation section 212. The lower end of the second straight pipe 23 has a liquid outlet 231. The tubular crystallizer 2 also includes a cooling jacket mounted on the straight pipes. The cooling jacket has a coolant inlet 206 and a coolant outlet 201. The coolant inlet 206 is located near the lower end of the second straight pipe 23, and the coolant outlet 201 is located near the upper end of the first straight pipe 21. The tubular crystallizer 2 also includes a first temperature sensor 24a for detecting the temperature of the crystallizing liquid in the lower end of the nucleation section 212, and the flow rate of the coolant in the cooling jacket is adjusted by the detection value of the first temperature sensor 24a.

[0042] Specifically, such as Figure 1 As shown, the lower end of the first straight pipe 21 is connected to the upper end of the second straight pipe 23 via a bend 22. Therefore, the flow path for the crystallizing liquid in this tubular crystallizer 2 mainly consists of two straight pipes and one bend 22. Both the first straight pipe 21 and the second straight pipe 23 are inclined, with the included angle between them and the horizontal being 10–45 degrees, and further 10–30 degrees. Figure 1 Specifically, the angle is 10 degrees. The centerlines of the first straight pipe 21 and the second straight pipe 23, as well as the centerline of the bend 22, lie in the same vertical plane. The first straight pipe 21 and the second straight pipe 23 are mirror-symmetrical in the vertical direction, that is, symmetrical about a horizontally extending axis. The bend 22 is an arc-shaped bend 22, and the arc formed by the bend 22 is a minor arc. The bend 22 and the straight pipe transition smoothly, that is, the middle part of the bend 22 arches towards the side farther from the straight pipe. Corresponding to Figure 1As shown, the bend 22 connects to the left side of the two straight pipes, and the middle of the bend 22 protrudes and arches to the left. Thus, the connection between the straight pipe and the bend 22 forms a fluid passage for the crystallizing liquid, and this fluid passage does not change abruptly at the connection between the straight pipe and the bend 22, ensuring that the crystallizing liquid flows slowly and uniformly throughout the entire fluid passage.

[0043] The length of the first straight pipe 21 and the second straight pipe 23 is 1–12 m, with an inner diameter of 20–200 mm and an outer diameter of 25–219 mm; the outer diameter of the cooling jacket is 45–273 mm. The inner diameter of the bent pipe 22 is equal to that of the first straight pipe 21 / second straight pipe 23, and the radius of curvature of the bent pipe 22 is 3 times or more, and further 3–8 times, the inner diameter of the first straight pipe 21 / second straight pipe 23. Only the upper part of the first straight pipe 21 serves as the nucleation section 212, in which a wall-mounted stirrer 26 is installed and an independent cooling jacket (i.e., the first cooling jacket mentioned below) is installed. By controlling the temperature of the coolant, nucleation occurs in the nucleation section 212, while the other parts of the first straight pipe 21, the bent pipe 22, and the second straight pipe 23 all serve as crystal growth regions, with the temperature in the metastable region.

[0044] The inner walls of the first straight pipe 21, the second straight pipe 23, and the bend 22 are mirror-polished with a surface roughness of less than 0.4. The first straight pipe 21 /

[0045] The second straight pipe 23 and the bend 22 are made of stainless steel, and the inner wall of the pipe is mirror-polished. The stainless steel pipe is 304 stainless steel. Alternatively, the inner wall of the first straight pipe 21 / second straight pipe 23 and bend 22 is provided with an enamel glass bushing. The first straight pipe 21 / second straight pipe 23 and bend 22 are made of S30408 ​​stainless steel.

[0046] The cooling jacket includes a first cooling jacket 20a, a second cooling jacket 20b, and a third cooling jacket 20c, each of which is a sleeve fitted onto a straight pipe. Specifically, the first cooling jacket 20a is fitted onto the nucleation section 212 of the first straight pipe 21, with a coolant outlet 201 located at its upper end and a first cooling inlet 202 located at its lower end. The second cooling jacket 20b is fitted onto the growth section 213 of the first straight pipe 21, with a second cooling outlet 203 at its upper end and a second cooling inlet 204 at its lower end. The third cooling jacket 20c has a third cooling outlet 205 at its upper end and a coolant inlet 206 located at its lower end.

[0047] The feed inlet 211 is connected to a high-temperature solution tank 1 storing the crystallizing liquid. A second temperature sensor 24b is installed at the feed inlet 211 or the high-temperature solution tank 1. A third temperature sensor 24c is installed in the middle of the bend 22. A fourth temperature sensor 24d is installed at the liquid outlet 231. A fifth temperature sensor 25e is installed at the coolant inlet 206, and a sixth temperature sensor 25f is installed at the coolant outlet 201. A first flow meter F1 is also installed at the liquid outlet 231, and a second flow meter F2 is also installed at the coolant outlet 201. The second cooling outlet 203 and the first cooling inlet 202 can be connected by a cooling water pipe, and the third cooling outlet 205 and the second cooling inlet 204 can be connected by a cooling water pipe. The bend 22 is equipped with a heat insulation layer. The first temperature sensor 24a measures the temperature T2 of the crystallizing liquid at the outlet of the nucleation section 212 of the first straight pipe 21; the second temperature sensor 24b measures the temperature T1 of the crystallizing liquid flowing through the feed inlet 211; the third temperature sensor 24c measures the temperature T3 of the crystallizing liquid flowing through the bend 22; the fourth temperature sensor 24d measures the outlet temperature T4 of the crystallizing liquid exiting from the liquid outlet 231; the fifth temperature sensor 25e measures the temperature t1 of the coolant flowing through the coolant inlet 206; and the sixth temperature sensor 25f measures the temperature t2 of the coolant flowing through the coolant outlet 201. The first flow meter F1 measures the outlet flow rate F1 of the crystallizing liquid, and the second flow meter F2 measures the outlet flow rate F2 of the cooling water.

[0048] The tubular crystallizer 2 also includes a disturbance device for agitating the liquid within the straight pipe and / or bend 22. This disturbance device includes a reciprocating pump 28 and a motor driving the reciprocating pump 28. The aforementioned liquid outlet 231 and the crystal grower 27 are connected via a pipe 271, with the reciprocating pump 28 mounted on the second straight pipe 23 or the pipe 271. A discharge valve 272 is provided at the lower end of the crystal grower 27.

[0049] The crystallization mechanism of the tubular crystallizer 2 is as follows:

[0050] Static crystallization, lacking the disruption of stirring, often yields larger crystals, which is more beneficial for subsequent separation, washing, and drying. Product purity and solution residue are generally also superior, but the process is time-consuming. In contrast, a tubular crystallizer utilizes its plug flow characteristics to ensure a slow, semi-static crystallization residence time (preferably preventing backmixing and breakage within the crystallizer) while simultaneously transferring heat to the material via cooling water at a controlled cooling rate. This prevents prolonged crystallization time, allowing the concentration and temperature to decrease simultaneously in a gradient until the crystallization endpoint is reached. Here, it is crucial to precisely match the residence time and cooling rate to ensure the entire cooling process remains within the metastable region. When the apparatus is fixed, the key control lies in matching the solution flow rate and the cooling water flow rate.

[0051] Setting the straight pipe at an inclination of 10 to 45 degrees can prevent crystals from depositing and clogging the pipe, while allowing the crystals to flow forward with the solution, but without the crystals flowing too fast.

[0052] A nucleation section 212 is installed inside the first straight pipe 21 to prevent crystal scaling. Adding seed crystals releases supersaturation into the crystals, preventing secondary nucleation and scaling. The crystal nuclei generated in the nucleation section 212 are equivalent to adding seed crystals to the subsequent growth section 213. A wall-scraping agitator 26 is installed in the nucleation section 212 (no agitation is used in other parts such as the growth section 213) to prevent secondary nucleation and crystal adhesion to the pipe wall. To prevent crystals from accumulating at the bottom of the pipe in the growth zone, wall adhesion experiments showed that pulses are beneficial for preventing adhesion. Therefore, a reciprocating pump 28 is installed to maintain relative motion between the crystals and the wall of the straight / bend pipe 22. The reciprocating pump 28 also has other functions: it can apply pulses to the crystallizing liquid in the pipe, causing the crystal slurry to move downwards along the inclined pipe wall at a certain speed; the pulse vibration of the crystal slurry can promote the transfer of concentration from the upper part of the pipe cross-section to the lower part, enhancing mass transfer; and the pulse vibration of the crystal slurry can promote the exchange of temperature between the inside and outside of the wall, enhancing heat transfer. The pulse quantity of the reciprocating pump (pulse frequency * plunger cross-sectional area) is 0.1% to 1% of the total fluid volume inside the tubular crystallizer; here, the total fluid volume inside the tubular crystallizer = the volume of the cavity of the first straight pipe 21 + the volume of the cavity of the bend 22 + the volume of the cavity of the second straight pipe 23.

[0053] The reciprocating pump 28 is installed in the pipeline between the second straight pipe 23 and the crystal grower 27, so the crystal slurry can also be discharged in a pulsed manner, and the crystal slurry is discharged at the same time as the crystal liquid in the straight pipe / bend pipe 22 is pulsed.

[0054] The coolant and the crystallizing liquid flow in a countercurrent manner, which allows the temperature to drop in a gradient, thus facilitating crystallization control.

[0055] Setting measurement points for the temperature and flow rate of the crystallizing liquid, as well as the inlet and outlet temperatures and flow rates of the coolant, facilitates calculation and control of the crystallization process.

[0056] A method for crystallizing biotin, using the aforementioned tubular crystallizer 2, includes the following steps: introducing biotin crystallizing liquid into a first straight pipe 21 through a feed inlet 211, introducing coolant into a cooling jacket through a coolant inlet 206, with the flow direction of the biotin crystallizing liquid being opposite to that of the coolant, and controlling the inlet flow rate of the biotin crystallizing liquid and the outlet flow rate of the coolant to reduce the concentration and temperature of the biotin crystallizing liquid according to a set gradient.

[0057] Biotin crystallization solution is prepared by dissolving crude biotin in water, wherein the purity (mass fraction) of biotin in the crude biotin is 90-96%.

[0058] The biotin mass fraction in the biotin crystallization solution is 0.8-1.1%, the feed temperature T1 is 88-100℃, the discharge flow rate F1 from the feed outlet 231 is 3-6 L / h, and the total residence time in the straight and bent pipes 22 is 0.4-2h.

[0059] The feed temperature t1 of the coolant (specifically cooling water) at the coolant inlet 206 is 18-28℃, and the flow rate F2 at the coolant outlet 201 is 3-6L / h. The flow rate of the coolant is adjusted according to the temperature value T2 detected by the first temperature sensor 24a.

[0060] Typically, a low concentration of biotin mother liquor is introduced into the tubular crystallizer as a base liquid before crystallization. This is to prevent the solution to be crystallized from directly entering the inner tube of the tubular crystallizer and crystallizing out directly due to the temperature setting of the coolant in the outer jacket.

[0061] Example 1

[0062] use Figure 1 The tubular crystallizer 2 shown is used for biotin crystallization. The first straight tube 21 and the second straight tube 23 are 1700 mm long and have an inner diameter of 24 mm. The radius of curvature of the bent tube 22 is five times that of the straight tube.

[0063] The crystallization process is as follows:

[0064] (1) Dissolve 5g of crude biotin (biotin mass fraction 92wt%) in 5L of water. The biotin mass fraction in the solution is about 0.09%. Heat to 99℃ to obtain the base solution, which is ready for use.

[0065] (2) Dissolve 315g of crude biotin (biotin mass fraction 92wt%) in 30L of water. The biotin mass fraction in the solution is about 0.96%. Heat to 99℃ to obtain a biotin solution to be crystallized and set aside for use.

[0066] (3) Fill the first straight pipe 21, the bend 22, the second straight pipe 23, and the crystallizer 27 with 35°C water. Pour material one into the high-temperature solution tank 1. The tank is electrically heated and kept warm. Turn on the stirrer and open the saturated liquid bottom valve. Adjust the discharge flow rate to 62 ml / min through the pulse discharge valve of the crystallizer 27. Material one replaces the water in the crystallizer, forming a temperature gradient. After the conversion of material one is completed, pour material two into the high-temperature solution pipe. Adjust the solution flow rate and the cooling water flow rate to keep the crystallization process in the metastable region. Complete the continuous experiment and take samples. The experimental data are shown in Table 1.

[0067] Table 1

[0068] parameter numerical values T1 / ℃ 99 T2 / ℃ 75 T3 / ℃ 57 T4 / ℃ 42 t1 / ℃ 24 t2 / ℃ 75 Rotational speed (r / min) 30 Pulse frequency 1 / s 1 Pulse stroke mm 2 F1 ml / min 62 F2 ml / min 70 yield 96.3％ Crystal purity 99.6％

[0069] See the photograph of the crystal liquid after discharge, taken under a 100x microscope. Figure 2It consists of needle-like crystals, with a crystal size of 3-4 mm and a bulk density > 0.55 g / cm³. 3 The compaction density is >0.95 g / cm³. 3 This meets the demand for high-end biotin.

[0070] Example 2

[0071] The difference between this embodiment and Embodiment 1 lies in the temperature gradient of the biotin crystallization solution. Specifically, T1 is 95°C, T2 is 73°C, T3 is 53°C, T4 is 40°C, t1 is 22°C, and t2 is 71°C. Everything else is basically the same as in Embodiment 1. The final product yield from crystallizer 27 is 96.8%, and the purity is 99.2%.

[0072] Example 3

[0073] The difference between this embodiment and Embodiment 1 is that the temperature gradient of the biotin crystallization solution is different. Specifically, T1 is 90°C, T2 is 70°C, T3 is 48°C, T4 is 38°C, t1 is 23°C, and t2 is 69°C. Everything else is basically the same as in Embodiment 1.

[0074] The final product yield from crystallizer 27 was 97.0%, with a purity of 99.0%. See the photograph of the crystal solution after discharge, taken under a 100x microscope. Figure 3 It consists of needle-like crystals, with a crystal size of 0.9–1.3 mm and a bulk density > 0.55 g / cm³. 3 The compaction density is >0.95 g / cm³. 3 This meets the demand for high-end biotin.

[0075] Comparative Example 1

[0076] The difference between Comparative Example 1 and Example 1 is that the biotin crystallization method is different, and biotin is processed by intermittent crystallization.

[0077] The crystallization process is as follows:

[0078] (1) Dissolve 315g of crude biotin (92wt% biotin) in 30L of water and heat to 99℃.

[0079] (2) Keep warm at 99℃ for 1 hour, and then cool in cold water after the warming is completed.

[0080] (3) After 0.5 hours, wait for the temperature to drop to 42℃, complete the experiment and take a sample.

[0081] The product yield from intermittent crystallization was 96.3%, with a purity of 98.7%. See the photograph of the cooled crystal solution taken under a 100x microscope. Figure 4 It consists of fine, powdery particles. The crystal size is 10–20 μm.

[0082] Conventional crystallization processes (such as those in Comparative Example 1) not only cannot achieve continuous production, but also have difficulty controlling the crystallization process, and are prone to nucleation explosions during crystallization, forming conditions such as... Figure 4 The powdery particles shown are difficult to separate by centrifugation, easily clog filter screens, and tend to clump together. Furthermore, their loose bulk density is 0.4-0.5 g / cm³. 3 The compaction density is 0.7-0.8 g / cm³. 3 This does not meet the demand for high-end biotin.

[0083] Comparative Example 2

[0084] The difference between Comparative Example 3 and Example 1 is that the temperature gradient of the biotin crystallization solution is different. Specifically, T1 is 99°C, T2 is 85°C, T3 is 74°C, T4 is 60°C, t1 is 30°C, and t2 is 65°C. Other aspects are basically the same as in Example 1.

[0085] The final product yield from crystal grower 27 was 85.2%, with a purity of 98.4%. The product yield was relatively low, and there was a significant amount of product carried over into the mother liquor.

[0086] The tubular crystallizer 2 and the biotin crystallization method of the embodiment, combined with the crystallization metastable zone curve, control the cooling rate and the crystal slurry residence time; this allows the crystals inside the tube to move forward rhythmically along the slope, and because there is no stirring in the crystal growth zone, secondary nucleation is greatly reduced, which is conducive to crystal growth; the crystal growth process all falls within the metastable zone, so crystal scaling will not occur; the high-temperature solution tank 1 is connected to the crystal grower 27 through the inclined straight pipe and bend pipe 22, which reduces the risk of pipe and valve blockage in conventional designs.

[0087] The above embodiments are merely illustrative of the technical concept and features of the present invention, and are preferred embodiments. Their purpose is to enable those skilled in the art to understand the content of the present invention and implement it accordingly, and they should not be construed as limiting the scope of protection of the present invention. All equivalent transformations or modifications made according to the principles of the present invention should be covered within the scope of protection of the present invention.

Claims

1. A tubular crystallizer, characterized in that, It includes several straight pipes and bends connected vertically, each of the straight pipes having an upper end and a lower end, and the bends connecting the lower end of one straight pipe to the upper end of another adjacent straight pipe. The plurality of straight tubes include a first straight tube and a second straight tube. The upper end of the first straight tube is provided with a feed inlet. The first straight tube has a nucleation section and a growth section. The growth section is not equipped with a stirrer. The lower end of the second straight tube is provided with a liquid outlet. The straight pipe has an angle of 10 to 45 degrees with the horizontal plane; the bend is an arc-shaped bend with a radius of curvature that is 3 times or more the inner diameter of the straight pipe, and the bend and the straight pipe transition smoothly. The tubular crystallizer further includes a cooling jacket disposed on the straight tube, the cooling jacket having a coolant inlet and a coolant outlet, the coolant inlet being close to the lower end of the second straight tube, and the coolant outlet being close to the upper end of the first straight tube; The tubular crystallizer also includes a first temperature sensor for detecting the temperature of the liquid material in the lower end of the nucleation section, and a stirrer is provided in the nucleation section.

2. The tubular crystallizer according to claim 1, characterized in that, The agitator is a wall-scraping agitator.

3. The tubular crystallizer according to claim 1, characterized in that, The cooling jacket includes a first cooling jacket disposed on the nucleation section of the first straight pipe, the coolant outlet is disposed at the upper end of the first cooling jacket, and a first cooling inlet is disposed at the lower end of the first cooling jacket.

4. The tubular crystallizer according to claim 3, characterized in that, The cooling jacket also includes a second cooling jacket disposed on the growth section of the first straight pipe and a third cooling jacket disposed on the second straight pipe. The upper end of the second cooling jacket is provided with a second cooling outlet and the lower end is provided with a second cooling inlet. The upper end of the third cooling jacket is provided with a third cooling outlet. The coolant inlet is disposed at the lower end of the third cooling jacket. The bend is provided with a heat insulation layer.

5. The tubular crystallizer according to claim 4, characterized in that, The second cooling outlet is connected to the first cooling inlet, and the third cooling outlet is connected to the second cooling inlet.

6. The tubular crystallizer according to claim 1, characterized in that, The tubular crystallizer also includes a disturbance device for agitating the liquid within the straight tube and / or the curved tube.

7. The tubular crystallizer according to claim 6, characterized in that, The disturbance device includes a reciprocating pump.

8. The tubular crystallizer according to claim 6 or 7, characterized in that, The tubular crystallizer also includes a crystal grower, which is connected to the liquid outlet via a pipeline, and the disturbance device is disposed on the second straight pipe or the pipeline.

9. The tubular crystallizer according to claim 1, characterized in that, The inner diameter of the bend is equal to the inner diameter of the straight pipe.

10. The tubular crystallizer according to claim 9, characterized in that, The centerlines of the straight pipes and the centerlines of the bent pipes are in the same vertical plane, and the radius of curvature of the bent pipe is 3 to 8 times the inner diameter.

11. The tubular crystallizer according to claim 1, characterized in that, The length of the straight pipe is 1~12m, the inner diameter of the straight pipe is 20~200mm, the outer diameter of the straight pipe is 25~219mm, the outer diameter of the cooling jacket is 45~273mm, the inner wall of the straight pipe and the bend is mirror polished and the roughness is less than 0.4; and / or, the feed inlet is connected to the high temperature solution tank; and / or, the lower end of the first straight pipe is connected to the upper end of the second straight pipe through a bend, a second temperature sensor is provided at the feed inlet, a third temperature sensor is provided at the bend, and a fourth temperature sensor is provided at the liquid outlet; a wall scraping agitator is provided in the nucleation section, the liquid outlet is connected to the crystal grower, a reciprocating pump is provided on the second straight pipe, a first flow meter is also provided at the liquid outlet, and a second flow meter is also provided at the coolant outlet.

12. A method for crystallizing biotin, characterized in that, Using the tubular crystallizer as described in any one of claims 1 to 11, the crystallization method includes the following steps: introducing biotin crystallization liquid into the straight pipe through the feed port; introducing coolant into the cooling jacket through the coolant inlet; the flow direction of the biotin crystallization liquid is opposite to the flow direction of the coolant; controlling the inlet flow rate of the biotin crystallization liquid and the outlet flow rate of the coolant to reduce the concentration and temperature of the biotin crystallization liquid according to a set gradient; wherein, a pulse quantity of 0.1% to 1% of the total fluid volume inside the tubular crystallizer is applied to the liquid in the second straight pipe by a reciprocating pump.

13. The crystallization method according to claim 12, characterized in that, The biotin crystallization solution contains 0.8-1.1% biotin by mass, has a feed temperature of 88-100°C, a discharge flow rate of 3-6 L / h from the liquid outlet, and a total residence time of 0.4-2 h in the straight and curved pipes; and / or, the coolant has a feed temperature of 18-28°C at the coolant inlet, a flow rate of 3-6 L / h at the coolant outlet, and the flow rate of the coolant is adjusted according to the temperature value detected by the first temperature sensor.

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