Vitamin D2 production method and device

Abstract

The invention provides an efficient vitamin D2 production method and a special device thereof, and aims to reduce invalid attenuation of ultraviolet light, improve the conversion rate of raw materials, reduce generation of impurities and improve the yield of finished products. The method comprises the following steps: preparing a reaction solution according to 1-2% of ergosterol, and maintaining the temperature at 20-25 DEG C; starting the tubular centrifuge to enable the reaction liquid to form thick-wall accumulation under the action of centrifugal force; turning on a high-pressure mercury lamp for illumination, and ensuring that the reaction liquid is uniformly illuminated through a spiral guide plate; and the illuminated reaction liquid flows back to the circulating transfer tank through the overflow pipe, is cooled and then is pumped into the centrifugal machine again, so that continuous circulation is formed. The high-pressure mercury lamp is directly arranged in the centrifugal machine, so that light path obstacles are reduced, the illumination intensity utilization rate is improved, the illumination time is shortened by more than 30% under the same conversion rate, the impurity rate is reduced to 3% or below, the comprehensive yield is improved to 42% or above, and the economic benefit of vitamin D2 production is remarkably improved; and especially, the method has important economic and social values for medicinal products.

Description

Technical Field

[0001] The invention relates to the technical field of chemical industry, and in particular to a method and a device for producing vitamin D2. Background Art

[0002] In the existing production process of vitamin D, the ring-opening reaction of ergosterol under ultraviolet light is the most critical process step that determines the product yield and product impurity content.

[0003] At present, there are two forms of light sources for UV light chemical reactions: one is high-pressure mercury lamps as UV light sources, and the other is LED UV band lamps as UV light sources. However, due to the high cost of LED UV lamps, most domestic companies use high-pressure mercury lamps.

[0004] There are two types of photochemical reactions: intermittent photochemical reactions and continuous flow photochemical reactions. The intermittent photochemical reaction device is shown in the attached manual. Figure 1 As shown, in order to isolate the high-pressure mercury lamp UV lamp tube from the reaction liquid and cool the heat released by the lamp tube, the lamp tube is placed in a quartz sleeve with a sandwich, and the lamp source coolant (cooling circulating water) passes through the sleeve sandwich, so that the ultraviolet light penetrates two layers of quartz tube wall (double-layer jacket) and a layer of coolant, and the light intensity is invalidly attenuated before entering the reaction liquid, so that the reaction liquid needs to extend the irradiation time to achieve a predetermined conversion rate. Extending the auxiliary irradiation time increases impurities, making purification more difficult and making it difficult to improve the overall yield. Summary of the invention

[0005] The technical problem to be solved by the present invention is to provide a method and device for producing vitamin D2, solve the problem of ineffective attenuation of ultraviolet light in existing photochemical reaction devices, improve the raw material conversion rate per unit time, reduce the amount of impurities generated, reduce the purification cost, and greatly improve the yield of finished products.

[0006] In order to solve the above technical problems, the technical solution adopted by the present invention is: a method for producing vitamin D2, characterized by comprising the following steps: S1. Prepare a mixed reaction solution of ethanol and the like according to 1-2% of the raw material ergosterol, and maintain the temperature at 20-25°C; S2, driving the centrifuge drum in the tubular centrifuge by electric power to a speed of 200-400 rpm, so that the centrifugal force of the reaction solution is greater than the gravity; S3, the reaction liquid is input from the bottom of the tubular centrifuge shell, and is continuously sprinkled toward the outer wall of the centrifuge tube through the distribution pipe, and under the action of centrifugal force, a thick wall of liquid is formed; S4. After the material output of the material distribution pipe and the material return of the material discharging pipe are balanced, the high-pressure mercury lamp tube vertically arranged in the tubular centrifuge is powered on and turned on until the current is stable; S5. After being irradiated by the adjacent ultraviolet light source, the reaction liquid is passively mixed by the spiral guide plate installed on the inner wall of the centrifuge drum, overflows from the overflow pipe above, and then flows back to the circulation transfer tank through the discharge pipe; S6. The refluxed reaction liquid is cooled to 15-25°C in the circulation transfer tank and then pumped back into the tubular centrifuge through the distribution pipe.

[0007] In a preferred embodiment, the residence time of the reaction liquid in the tubular centrifuge is controlled by the discharge speed of the distribution pipe; The discharge speed of the distribution pipe is inversely proportional to the residence time of the reaction liquid in the tubular centrifuge.

[0008] In a preferred embodiment, the temperature of the reaction liquid overflowing from the overflow pipe is no more than 30°C.

[0009] In a preferred embodiment, during the circulation of the reaction solution, the circulation reaction ends after the conversion rate of ergosterol, the raw material of the reaction solution, into previtamin D2 reaches 55-60%.

[0010] In a preferred embodiment, after the cycle reaction is completed, a new round of photochemical reaction is continuously carried out by switching the cycle transfer tank connected to the cycle system without stopping the machine.

[0011] In a preferred embodiment, after the cyclic reaction is completed, the high-pressure mercury lamp is turned off and after the centrifuge drum is decelerated to a stationary state, the reaction liquid is collected and the operation is terminated.

[0012] A production device based on the above vitamin D2 production method includes a tubular centrifuge, wherein a centrifuge tube drum is provided in the tubular centrifuge, the centrifuge tube drum is driven by a hollow drive shaft in cooperation with a drive device, and a high-pressure mercury lamp is provided in the middle of the centrifuge tube drum; A distribution pipe is inserted into the hollow driving shaft driving the centrifuge tube drum, the distribution pipe outlet is arranged horizontally and facing the centrifuge tube drum, and the distribution pipe is connected to the outlet of the circulation transfer tank; The centrifuge drum is also fixedly provided with two symmetrical overflow pipes, the inlets of which are located at the upper part of the centrifuge drum, and the overflow pipes are used to overflow the rising reaction liquid in the centrifuge drum into the tubular centrifuge housing; A discharge pipe connected to the circulation transfer tank is arranged on the inner bottom surface of the tubular centrifuge housing.

[0013] In a preferred embodiment, a spiral guide plate is provided on the inner wall of the centrifuge tube drum, and the spiral guide plate is used to make the reaction liquid flip and flow along the spiral guide plate when the reaction liquid is pushed upward on the centrifuge tube drum, so as to achieve uniform irradiation of the reaction liquid.

[0014] In a preferred embodiment, the high-pressure mercury lamp tube extends from the top of the tubular centrifuge and is fixedly arranged.

[0015] In a preferred embodiment, a jacket is provided on the outside of the circulating transfer tank, and a coolant is introduced into the jacket to achieve the purpose of cooling the circulating reaction liquid.

[0016] The vitamin D2 production method and device provided by the present invention solves the problem of obstruction between the light source and the reaction liquid by adopting the above method and structure, and greatly improves the utilization rate of ultraviolet light by more than 35%. The conversion rate of the same raw materials shortens the illumination time by more than 30%, and the impurity rate is reduced from the original 4-5% to less than 3%, so that the purification procedure of the illumination reaction liquid is simplified, and the comprehensive yield of the finished product is increased from 30-33% (including ergosterol recycling) in the traditional way to more than 42%. Since medicinal vitamin D2 is expensive, the economic benefits thus improved are very significant.

[0017] The process scheme of the present invention can also be applied to the production of vitamin D3, specifically, the ergosterol reaction solution is replaced with 7-dehydrocholesterol reaction solution, and the reaction temperature is maintained at 35-40°C by controlling the circulation flow rate of the reaction solution. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The present invention will be further described below in conjunction with the accompanying drawings and embodiments: Figure 1 It is a schematic diagram of the structure of an existing intermittent photochemical reaction device.

[0019] Figure 2 It is a schematic diagram of the device structure of the present invention.

[0020] In the figure: a high-pressure mercury lamp tube 1, a distribution pipe 2, an overflow pipe 3, a spiral guide plate 4, a discharge pipe 5, a centrifuge drum 6, a tubular centrifuge 7, a reaction liquid 8, and a circulation transfer tank 9. DETAILED DESCRIPTION

[0021] Embodiment 1: In the 60L No. 1 reaction liquid circulation transfer tank 9 (316L stainless steel), add 49.97L of ethanol solvent, 503.1g of ergosterol raw material and 35.0g of photosensitizer to prepare a reaction liquid. Under stirring, adjust the temperature of the reaction liquid to stabilize at 20-22°C for use.

[0022] Start the tubular centrifuge 7 (tube diameter 200mm, tube length 500mm, hollow diameter 100mm, symmetrical spacing of two overflow pipes 3 110mm) and control the speed at 353 rpm (digital display). Pump the reaction liquid (21.7℃) continuously from the lower end distribution pipe 2 into the reaction liquid 8 until it accumulates in the upper overflow pipe 3. When the reaction liquid 8 overflows, vertically insert a C-type 1 kW high-pressure mercury lamp (mercury lamp total length 400mm) from the hollow slot of the tubular centrifuge 7, turn on the power supply for continuous irradiation. The distribution speed is controlled at about 1500ml / min (rotor flowmeter) through the valve on the distribution pipe 2, and the overflow material temperature is 26.6℃ (digital display). The reaction liquid can be accumulated to a thickness of 90mm (200mm-110mm), and the total volume of the reaction liquid can be accumulated to 11L.

[0023] After the overflow liquid is guided back to the reaction liquid circulation transfer tank, the reaction liquid is cooled to 20-25°C under stirring, and then continuously pumped into the distribution pipe to form a continuous cycle. Referring to the test data of continuous reaction for 8 hours, the machine is shut down after 10 hours of continuous reaction, and all the reaction liquid is collected for post-processing.

[0024] When the photochemical reaction continued for 8 hours, 9 hours, and 10 hours, samples were taken from the circulation tank for testing. The conversion rates of the raw material ergosterol were as follows: Table 1. UV irradiation and ergosterol conversion rate

[0025] Embodiment 2: In the 60L No. 2 reaction liquid circulation transfer tank 9, 50.97L of ethanol solvent, 503.4g of ergosterol raw material and 35.0g of photosensitizer were added to prepare a reaction liquid. Under stirring, the temperature of the reaction liquid was adjusted to be stable at 20-22°C for standby use.

[0026] Start the tubular centrifuge 7 and control the speed at 348 rpm (digital display). Pump the reaction liquid (20.2°C) from the lower distribution pipe 2 into the reaction liquid 8 continuously until it accumulates in the upper overflow pipe 3. When the reaction liquid 8 overflows, vertically place a C-type 1 kW high-pressure mercury lamp in the hollow slot of the tubular centrifuge 7, turn on the power and irradiate continuously. The distribution speed is controlled at about 1500 ml / min (rotor flowmeter) through the valve on the distribution pipe 2, and the overflow material temperature is 26.1°C (digital display).

[0027] After the overflow liquid is guided back to the reaction liquid circulation transfer tank 9, the reaction liquid is cooled to 20-25°C under stirring, and then continuously pumped into the distribution pipe 2 to form a continuous cycle. After 9 hours of continuous reaction, the machine is shut down and all the reaction liquid is collected for post-processing.

[0028] After shutdown, samples were taken from the circulation tank for testing. The conversion rate of raw material ergosterol was shown in Table 2.

[0029] Embodiment 3: In the No. 1 60L reaction liquid circulation transfer tank 9, add 49.71L of ethanol solvent, 503.4g of ergosterol raw material and 35.0g of photosensitizer to prepare a reaction liquid. Under stirring, adjust the temperature of the reaction liquid to be stable at 20-22°C for standby use.

[0030] Start the tubular centrifuge 7 and control the speed at 350 rpm (digital display). Pump the reaction liquid (20.6°C) from the lower end distribution pipe 2 into the reaction liquid 8 continuously until it accumulates in the upper overflow pipe 8. When the reaction liquid 8 overflows, vertically place a C-type 1 kW high-pressure mercury lamp from the hollow slot of the tubular centrifuge 7, turn on the power and irradiate continuously. The distribution speed is controlled at about 1500 ml / min (rotor flowmeter) through the valve on the distribution pipe 2, and the overflow material temperature is 26.4°C (digital display).

[0031] After the overflow liquid is guided back to the reaction liquid circulation transfer tank 9, the reaction liquid 8 is cooled to a temperature within the range of 20-25°C under stirring, and then continuously pumped into the distribution pipe 2 to form a continuous cycle.

[0032] After 9 hours of continuous reaction, the machine was switched from the No. 1 reaction liquid circulation transfer tank to the No. 2 reaction liquid circulation transfer tank, which had been freshly prepared with 50L of reaction liquid, and the circulating illumination was continued for 9.5 hours without stopping. Then, the No. 2 reaction liquid circulation transfer tank was immediately switched back to the No. 1 reaction liquid circulation transfer tank, which had been freshly prepared with 50L of reaction liquid, and the circulating illumination was continued for 9.5 hours without stopping.

[0033] The reaction liquids that have completed timed light irradiation are combined and collected and sent to the subsequent processing section.

[0034] After the shutdown, mixed samples of reaction liquid from three batches of circulating tanks were taken for testing. The conversion rates of raw material ergosterol are shown in Table 2.

[0035] Table 2. UV light operation parameters and results

[0036] From the above table we can know: The tubular centrifuge combined with the continuous flow illumination reaction method adopted by the present invention can more efficiently utilize the ultraviolet light source compared with the traditional intermittent operation method. By maintaining the continuous circulation of the reaction liquid, each part of the reaction liquid can be evenly and fully exposed to light, thereby improving the conversion rate of ergosterol.

[0037] The high-pressure mercury lamp is placed vertically directly into the hollow slot of the reaction liquid, minimizing obstacles in the light path (such as the quartz sleeve interlayer and coolant), thereby reducing the ineffective attenuation of light intensity, allowing more ultraviolet light to effectively act on the reaction liquid, and improving the utilization rate of light intensity. This design not only improves the conversion rate of the raw material ergosterol, but also shortens the illumination time required to achieve the same conversion rate, thereby reducing the possibility of impurity generation.

[0038] The data showed that even after a long period (19 hours) of continuous illumination, a low impurity rate (1.9%) was still maintained and a high ergosterol conversion rate (58.9%) was obtained.

Claims

1. A method for producing vitamin D2, characterized in that The following steps are involved: S1. Prepare a mixed reaction solution of ethanol and the like according to 1-2% of the raw material ergosterol, and maintain the temperature at 20-25°C; S2, driving the centrifuge drum (6) in the tubular centrifuge (7) by electric power to a speed of 200-400 rpm, so that the centrifugal force of the reaction liquid is greater than the gravity; S3, the reaction liquid is input from the bottom of the tubular centrifuge housing (7), and is continuously sprinkled toward the outer wall of the centrifuge tube through the distribution pipe (2), so that a thick wall of liquid is formed under the action of centrifugal force; S4. After the material output from the material distribution pipe (2) and the material return from the material discharging pipe (5) are balanced, the high-pressure mercury lamp tube (1) vertically arranged in the tubular centrifuge (7) is powered on and turned on until the current is stable; S5, after being irradiated by the adjacent ultraviolet light source, the reaction liquid (8) is passively mixed by the spiral guide plate (4) installed on the inner wall of the centrifuge drum (6), overflows from the overflow pipe (3) above, and then flows back to the circulation transfer tank (9) through the discharge pipe (5); S6. The refluxed reaction liquid is cooled to 15-25°C in the circulation transfer tank (9) and then pumped back into the tubular centrifuge (7) through the distribution pipe (2).

2. The method for producing vitamin D2 according to claim 1, characterized in that: Controlling the residence time of the reaction liquid (8) in the tubular centrifuge (7) by adjusting the discharge speed of the distribution pipe (2); The discharge speed of the distribution pipe (2) is inversely proportional to the residence time of the reaction liquid (8) in the tubular centrifuge (7).

3. The method for producing vitamin D2 according to claim 2, characterized in that: The temperature of the reaction liquid (8) overflowing from the overflow pipe (3) is not greater than 30°C.

4. The method for producing vitamin D2 according to claim 1, characterized in that: During the circulation of the reaction solution (8), the circulation reaction ends when the conversion rate of the raw material ergosterol in the reaction solution (8) into previtamin D2 reaches 55-60%.

5. The method for producing vitamin D2 according to claim 4, characterized in that: After the cycle reaction is completed, a new round of photochemical reaction is continuously carried out by switching the cycle transfer tank (9) connected to the cycle system without stopping the machine.

6. The method for producing vitamin D2 according to claim 4, characterized in that: After the cyclic reaction is completed, the high-pressure mercury lamp (1) is turned off and after the centrifuge drum (6) is decelerated to a stationary state, the reaction liquid (8) is collected and the operation is terminated.

7. A production device based on the vitamin D2 production method according to any one of claims 1 to 6, characterized in that: The invention comprises a tubular centrifuge (7), wherein a centrifuge tube drum (6) is arranged inside the tubular centrifuge (7), the centrifuge tube drum (6) is driven by a hollow drive shaft in cooperation with a drive device, and a high-pressure mercury lamp tube (1) is arranged in the middle of the centrifuge tube drum (6); A material distribution pipe (2) is inserted into the hollow drive shaft for driving the centrifuge tube drum (6), the material distribution pipe (2) has a discharge port arranged horizontally and facing the centrifuge tube drum (6), and the material distribution pipe (2) is connected to the discharge port of the circulation transfer tank (9); A plurality of overflow pipes (3) are also fixedly arranged on the centrifuge tube drum (6), the inlet of the overflow pipe (3) being located at the upper part of the centrifuge tube drum (6), and the overflow pipe (3) being used to overflow the reaction liquid (8) rising in the centrifuge tube drum (6) into the tubular centrifuge (7); A discharge pipe (5) connected to a circulation transfer tank (9) is provided on the bottom surface of the tubular centrifuge (7).

8. A vitamin D2 production device according to claim 7, characterized in that: A spiral guide plate (4) is provided on the inner wall of the centrifuge tube drum (6). The spiral guide plate (4) is used to cause the reaction liquid (8) to turn and flow along the spiral guide plate (4) when the reaction liquid (8) on the centrifuge tube drum (6) is pushed upward, so as to achieve uniform irradiation of the reaction liquid (8).

9. A vitamin D2 production device according to claim 7, characterized in that: The high-pressure mercury lamp tube (1) extends into and is fixedly arranged from the top of the tubular centrifuge (7).

10. A vitamin D2 production device according to claim 7, characterized in that: The circulation transfer tank (9) is provided with a jacket on the outside, and a cooling liquid is passed into the jacket to achieve the purpose of cooling the circulating reaction liquid (8).

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