Method for recovering mother liquor after purifying crude product of vitamin D3 or metabolic derivative thereof

Abstract

The invention discloses a method for recovering mother liquor after purification of crude products of vitamin D3 or metabolic derivatives thereof. Comprising the following steps: evaporating mother liquor obtained by purifying a crude cholecalciferol or calcifediol product to remove a solvent so as to obtain an oily concentrate, adding the oily concentrate into high-boiling-point grease, uniformly mixing, and collecting and recovering cholecalciferol or calcifediol by using a molecular distillation technology. According to the method, the molecular distillation technology is utilized to efficiently recover the cholecalciferol or the calcifediol, so that the content of the cholecalciferol or the calcifediol in the cholecalciferol or the calcifediol resin oil is increased to 80% or above, the recovery rate of the cholecalciferol or the calcifediol is 90% or above, the process is simple, the flow is short, the processing process is a physical separation process, and the method is suitable for industrial production. And no chemical substance harmful to the human body is added.

Description

Technical Field

[0001] This invention belongs to the field of separation and purification technology, specifically relating to a method for recovering cholecalciferol from the mother liquor after purifying crude vitamin D3 or its metabolic derivatives, applicable to the pharmaceutical, food and health product industries. Background Technology

[0002] Vitamin D3 (cholecalciferol) is primarily synthesized by the skin under ultraviolet B (UVB) radiation, and can also be obtained through food and supplements. Its main functions include aiding in the absorption of calcium and phosphorus in the intestines, maintaining bone health, and preventing rickets and osteoporosis. Further research on cholecalciferol has shown its important roles in immune regulation and chronic disease prevention. Calcidiol (25-hydroxyvitamin D3) is a metabolic derivative of vitamin D3. Compared to vitamin D3, it has an added hydroxyl group, enhancing its water solubility and making it easier to circulate in the blood. Its biological activity is 3-5 times that of vitamin D3, and it is more easily absorbed, directly from the intestines into the bloodstream. Calcidiol has significant effects on metabolic bone diseases such as osteoporosis, rickets, and osteomalacia, and can also be used to treat hypocalcemia caused by hemodialysis. It is also used as a raw material for health foods and feed additives, with wide applications in health foods, pharmaceuticals, and feed additives.

[0003] Currently, there are few reported processes for reusing the mother liquor after the separation and purification of vitamin D3 and its metabolic derivatives. Patent CN114380726A uses the purified mother liquor as raw material, converting the tachysterols in it into pre-vitamin D3 through a photochemical reaction, and then generating vitamin D3 through a thermal isomerization reaction, thereby increasing the vitamin D3 content in the mother liquor. Patent CN110527700A involves two types of crystallization mother liquors: one, crude vitamin D3 undergoes an esterification reaction to obtain vitamin D3 ester, and the crystallized vitamin D3 ester mother liquor is concentrated, saponified, and thermally isomerized to obtain feed-grade vitamin D3; the other, vitamin D3 ester crystals are saponified, extracted, and crystallized to obtain refined vitamin D3, and the crystallized mother liquor is concentrated and thermally isomerized for reuse as a substrate. Patent CN103044301A uses 25-hydroxy-7-dehydrocholesterol as raw material, separating and recovering 25-hydroxy-7-dehydrocholesterol after light irradiation, and then thermally isomerizing the remaining reactants after raw material recovery, followed by recrystallization to obtain calcidiol. The mother liquor produced after crystallization, separation and purification still contains residual products, intermediate products and by-products. Summary of the Invention

[0004] To address the problems in the prior art, the present invention aims to provide a method for recovering the mother liquor after purifying crude vitamin D3 or its metabolic derivatives. The present invention uses molecular distillation technology to increase the content of cholecalciferol or calcidiol in the mother liquor after crude product purification, thereby maximizing the yield of pure cholecalciferol or calcidiol and improving economic efficiency.

[0005] To achieve the above objectives, the present invention provides a method for recovering the mother liquor after purifying crude vitamin D3 or its metabolic derivatives, the method comprising the following steps: (1) After purifying the crude cholecalciferol or calcidiol, the mother liquor was evaporated to remove the solvent and an oily concentrate was obtained. (2) Add the oily concentrate to the high-boiling-point oil to dissolve it and mix well; (3) Collect and recover cholecalciferol or calcidiol resin oil from high-boiling-point oil solutions containing oily concentrates using molecular distillation technology.

[0006] After molecular distillation, the purity of cholecalciferol or calcidiol resin oil collected was increased from the initial content of 5-50 wt% to more than 80 wt% by HPLC analysis, and the recovery rate of cholecalciferol or calcidiol was more than 90 wt%.

[0007] Furthermore, in step (1), the mother liquor after separation and purification of cholecalciferol or calcidiol refers to the crude cholecalciferol or calcidiol processed through multiple purification steps, including extraction, column chromatography, chemical purification, and crystallization (one or more combined processes), to obtain pure cholecalciferol or calcidiol. This process includes at least a crystallization step, which is the final purification step. This step involves dissolving, crystallizing, and separating high-purity cholecalciferol or calcidiol solids in a specific solvent system to ultimately obtain pure cholecalciferol or calcidiol that meets pharmacopoeia standards, while simultaneously producing a mother liquor containing residual active ingredients. The raw material used in this invention is precisely the cholecalciferol or calcidiol mother liquor produced after the crystallization step.

[0008] Furthermore, in step (1), the content of cholecalciferol or calcidiol in the oily concentrate is 5-50 wt%.

[0009] Furthermore, in step (1), the conditions for removing the solvent from the mother liquor are a temperature of 30℃~80℃ and a vacuum of ≤-0.05 MPa; preferably, the temperature is 50℃~70℃ and the vacuum is ≤-0.08 MPa.

[0010] Furthermore, in step (2), the high-boiling-point oil is mineral oil or vegetable oil.

[0011] Furthermore, in step (2), the mineral oil is liquid paraffin or solid paraffin, preferably solid paraffin.

[0012] Furthermore, in step (2), the vegetable oil is one or more of the following: rapeseed oil, soybean oil, cottonseed oil, sunflower seed oil, peanut oil, palm oil, corn oil, sesame oil, flaxseed oil, rice bran oil, tea oil, and olive oil. Furthermore, in step (2), the volume of high-boiling-point oil used is usually 1~10 mL / g based on the mass of the concentrate; preferably 4~6 mL / g.

[0013] Furthermore, in step (3), the molecular distillation technique involves removing low-boiling-point substances through primary molecular distillation, obtaining cholecalciferol or calcidiol resin oil through secondary molecular distillation, or removing impurities with slightly lower boiling points through secondary molecular distillation, and collecting cholecalciferol or calcidiol resin oil through tertiary molecular distillation.

[0014] Furthermore, in step (3), the pretreated mother liquor is subjected to primary molecular distillation, and the distillation pressure is controlled at 50~80 Pa; preferably 60~70 Pa.

[0015] Furthermore, in step (3), the pretreated mother liquor is subjected to primary molecular distillation, and the feed flow rate is adjusted to 5~20 g / min, and the molecular distillation scraper rotation speed is 150~300 rpm.

[0016] Furthermore, in step (3), the pretreated mother liquor is subjected to primary molecular distillation, with the preheating temperature controlled at 30~60℃, the distillation temperature at 70~100℃, and the condensation temperature at 30~50℃; preferably, the preheating temperature is 60~70℃, the distillation temperature is 80~90℃, and the condensation temperature is 35~45℃.

[0017] Furthermore, in step (3), the heavy phase obtained from the primary molecular distillation product is subjected to a second molecular distillation, and the distillation pressure is controlled at 5~20 Pa; preferably 10~15 Pa.

[0018] Furthermore, in step (3), the heavy phase obtained from the primary molecular distillation product is subjected to a second molecular distillation, and the rotation speed of the molecular distillation scraper is 180~300 rpm.

[0019] Furthermore, in step (3), the heavy phase obtained from the primary molecular distillation product is subjected to a second molecular distillation, with the preheating temperature controlled at 50~80℃, the distillation temperature at 170~240℃, and the condensation temperature at 50~100℃; preferably, the preheating temperature is 55~70℃, the distillation temperature is 180~220℃, and the condensation temperature is 70~80℃.

[0020] Furthermore, in step (3), the heavy phase obtained from the secondary molecular distillation product is subjected to a third molecular distillation, and the distillation pressure is controlled at 0~1 Pa; preferably, the pressure is 0~0.5 Pa.

[0021] Furthermore, in step (3), the heavy phase obtained from the secondary molecular distillation product is subjected to a third molecular distillation, and the rotation speed of the molecular distillation scraper is 200~300 rpm.

[0022] Furthermore, in step (3), the heavy phase obtained from the secondary molecular distillation product is subjected to a third molecular distillation, with the preheating temperature controlled at 50~80℃, the distillation temperature at 210~280℃, and the condensation temperature at 70~100℃; preferably, the preheating temperature is 55~70℃, the distillation temperature is 220~270℃, and the condensation temperature is 75~95℃.

[0023] Furthermore, the mass percentage of cholecalciferol or calcidiol after molecular distillation is over 80%. The crude cholecalciferol obtained can be further purified and crystallized to yield pure cholecalciferol or calcidiol.

[0024] Compared with the prior art, the beneficial effects of the present invention are as follows: In existing technologies, the mother liquor concentrate produced during the separation and purification of cholecalciferol is typically treated in two ways: one is to reuse the material as a raw material in the upstream process, but this method is complex and requires a large amount of solvent; the other is to convert it into feed-grade raw material, but this method has drawbacks such as high impurity levels and unverifiable biosafety. Therefore, this invention uses molecular distillation technology to directly increase the cholecalciferol content in the mother liquor, using the crude product for the next crystallization step to obtain pure cholecalciferol. This maximizes the green benefits, avoids potential risks, fully utilizes the value of the process product, and improves economic efficiency.

[0025] The calcidiol resin oil obtained by this invention can be incorporated into the calcidiol crude crystallization process, improving the yield of calcidiol and reducing raw material consumption. Research on the reuse of calcidiol mother liquor not only improves production efficiency but also reduces production costs, representing an important path to achieving green manufacturing and sustainable development. Furthermore, research on the reuse of mother liquor after calcidiol crystallization helps to improve the closed-loop system of the entire calcidiol production process, providing technical reference for green production in the industry. Detailed Implementation

[0026] To make the technical solutions and advantages of the present invention clearer, the present invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are only for explaining the present invention and are not intended to limit the present invention.

[0027] Example 1 The mother liquor after separation and purification of cholecalciferol was evaporated at 55℃ under vacuum of -0.08 MPa to remove the solvent, yielding 1 kg of oily concentrate (cholecalciferol content 8.6%). 2 L of dissolved solid paraffin was added, and the mixture was thoroughly mixed at 70℃ and maintained at 70℃ before being fed into a secondary molecular distillation apparatus. The primary system pressure was 50 Pa, the scraped-film rotor speed was 150 rpm, and the feed rate was 10 mL / min. The distillation temperature was controlled at 70℃, and the condensation temperature at 35℃. The light phase, including small molecule hydrocarbons, was collected. The heavy phase, maintained at 60℃, was then fed into the secondary molecular distillation apparatus. The secondary system pressure was 0.4 Pa, the scraped-film rotor speed was 200 rpm, the distillation temperature was 245℃, and the condensation temperature at 80℃. The collected light phase was cholecalciferol resin oil with a cholecalciferol content of 86.6%, totaling 92.6 g, with a recovery rate of 93.2%.

[0028] Example 2 After separating and purifying cholecalciferol, the mother liquor was evaporated at 55℃ under a vacuum of -0.08 MPa to remove the solvent, yielding 1 kg of oily concentrate (cholecalciferol content 15.6%). This concentrate was mixed with 2 L of soybean oil and kept at 55℃ before entering a three-stage molecular distillation apparatus. In the first stage, the system pressure was 50 Pa, the scraper rotor speed was 150 rpm, and the feed rate was 10 mL / min. The distillation temperature was controlled at 70℃, and the condensation temperature at 35℃. The light phase, including small molecule hydrocarbons and low-chain fatty acids, was collected. The heavy phase, held at 50℃, entered the second stage of molecular distillation. In the second stage, the system pressure was 20 Pa, the scraper rotor speed was 180 rpm, the distillation temperature was controlled at 175℃, and the condensation temperature at 70℃. The light phase, including tachysterols, photosterols, and long-chain fatty acids, was collected. The heavy phase, held at 60℃, entered the third stage of molecular distillation. In the third stage, the system pressure was 0.8 Pa, and the scraper rotor speed was 200 rpm. The distillation process was carried out at rpm, with a distillation temperature of 245℃ and a condensation temperature of 80℃. The collected light phase was cholecalciferol resin oil with a cholecalciferol content of 82.6%, totaling 142.2g, and the recovery rate was 91.2%.

[0029] Example 3 After separating and purifying cholecalciferol, the mother liquor was evaporated at 55℃ under a vacuum of -0.08 MPa to remove the solvent, yielding 1 kg of oily concentrate (cholecalciferol content 24.8%). This concentrate was mixed with 4 L of peanut oil and kept at 55℃ before entering a three-stage molecular distillation apparatus. In the first stage, the system pressure was 50 Pa, the scraper rotor speed was 160 rpm, and the feed rate was 15 mL / min. The distillation temperature was controlled at 75℃, and the condensation temperature at 40℃. The light phase, including small molecule hydrocarbons and low-chain fatty acids, was collected. The heavy phase, held at 60℃, entered the second stage of molecular distillation. In the second stage, the system pressure was 15 Pa, the scraper rotor speed was 200 rpm, the distillation temperature was controlled at 180℃, and the condensation temperature at 75℃. The light phase, including tachysterols, photosterols, and long-chain fatty acids, was collected. The heavy phase, held at 60℃, entered the third stage of molecular distillation. In the third stage, the system pressure was 0.5 Pa, and the scraper rotor speed was 240 rpm. The distillation process was carried out at rpm, with a distillation temperature of 230℃ and a condensation temperature of 75℃. The collected light phase was cholecalciferol resin oil with a cholecalciferol content of 91.6%, totaling 255.9g, and the recovery rate was 94.5%.

[0030] Example 4 The mother liquor after calcidiol separation and purification was evaporated at 55 °C under a vacuum of -0.08 MPa to remove the solvent, yielding 1.5 kg of oily concentrate (calcidiol content 19%). 3 L of melted solid paraffin was added and stirred until homogeneous. The mixture was then kept at 60 °C and fed into a secondary molecular distillation apparatus. The primary system pressure was 60 Pa, the scraped-film rotor speed was 200 rpm, and the feed rate was 8 mL / min. The distillation temperature was controlled at 75 °C, and the condensation temperature at 40 °C. The light phase was collected, and the heavy phase was kept at 60 °C before entering the secondary molecular distillation apparatus. The secondary system pressure was 0.2 Pa, the scraped-film rotor speed was 200 rpm, the distillation temperature was 250 °C, and the condensation temperature was 95 °C. The collected light phase was calcidiol resin oil with a calcidiol content of 85%, totaling 316.28 g, with a recovery rate of 94.33%.

[0031] Example 5 The mother liquor after calcidiol separation and purification was evaporated at 55 °C under a vacuum of -0.08 MPa to remove the solvent, yielding 1.2 kg of oily concentrate (calcidiol content 8%). This concentrate was mixed with 4.8 L of peanut oil and kept at 60 °C before entering a tertiary molecular distillation apparatus. In the first stage, the system pressure was 60 Pa, the scraper rotor speed was 300 rpm, and the feed rate was 10 mL / min. The distillation temperature was controlled at 75 °C, and the condensation temperature at 40 °C. The light phase was collected, and the heavy phase was kept at 60 °C before entering the second stage of molecular distillation. In the second stage, the system pressure was 10 Pa, the scraper rotor speed was 200 rpm, the distillation temperature was 200 °C, and the condensation temperature was 90 °C. The light phase was collected, and the heavy phase was kept at 80 °C before entering the third stage of molecular distillation. In the third stage, the system pressure was 0.5 Pa, the scraper rotor speed was 200 rpm, the distillation temperature was 260 °C, and the condensation temperature was 95 °C. The collected light phase was calcidiol resin oil at ℃, with a calcidiol content of 88%, totaling 103.94 g, and a recovery rate of 95.28%.

[0032] Example 6 The mother liquor after calcidiol separation and purification was evaporated at 55 °C under a vacuum of -0.08 MPa to remove the solvent, yielding 1.0 kg of oily concentrate (calcidiol content 26%). This concentrate was mixed with 6.0 L of rapeseed oil and kept at 60 °C before entering a three-stage molecular distillation apparatus. In the first stage, the system pressure was 60 Pa, the scraper rotor speed was 200 rpm, and the feed rate was 15 mL / min. The distillation temperature was controlled at 75 °C, and the condensation temperature at 40 °C. The light phase was collected, and the heavy phase was kept at 60 °C before entering the second stage of molecular distillation. In the second stage, the system pressure was 15 Pa, the scraper rotor speed was 200 rpm, the distillation temperature was 210 °C, and the condensation temperature was 90 °C. The light phase was collected, and the heavy phase was kept at 80 °C before entering the third stage of molecular distillation. In the third stage, the system pressure was 0.8 Pa, the scraper rotor speed was 200 rpm, the distillation temperature was 270 °C, and the condensation temperature was 95 °C. The collected light phase was calcidiol resin oil at ℃, with a calcidiol content of 83%, totaling 292.89 g, and a recovery rate of 93.5%.

[0033] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the present invention in any way. Other variations and modifications are possible without departing from the technical solutions described in the claims.

Claims

1. A method for recovering mother liquor after purifying crude vitamin D3 or its metabolic derivatives, characterized in that, The method includes the following steps: (1) After purifying the crude cholecalciferol or calcidiol, the mother liquor was evaporated to remove the solvent and an oily concentrate was obtained. (2) Add the oily concentrate to the high-boiling-point oil to dissolve it and mix well; (3) Collect and recover cholecalciferol or calcidiol resin oil from high-boiling-point oil solutions containing oily concentrates using molecular distillation technology.

2. The method for recovering mother liquor after purifying crude vitamin D3 or its metabolic derivatives according to claim 1, characterized in that, In step (1), the oily concentrate contains 5-50% cholecalciferol or calcidiol.

3. The method for recovering mother liquor after purifying crude vitamin D3 or its metabolic derivatives according to claim 1, characterized in that, In step (2), the high-boiling-point oil is mineral oil or vegetable oil.

4. The method for recovering mother liquor after purifying crude vitamin D3 or its metabolic derivatives according to claim 1, characterized in that, In step (3), the molecular distillation technique is to remove low-boiling-point substances by primary molecular distillation, obtain cholecalciferol or calcidiol resin oil by secondary molecular distillation, or remove impurities with slightly lower boiling points by secondary molecular distillation, and collect cholecalciferol or calcidiol resin oil by tertiary molecular distillation.

5. The method for recovering mother liquor after purifying crude vitamin D3 or its metabolic derivatives according to claim 3, characterized in that, The mineral oil is liquid paraffin or solid paraffin.

6. The method for recovering mother liquor after purifying crude vitamin D3 or its metabolic derivatives according to claim 3, characterized in that, The vegetable oil is one or more of the following: rapeseed oil, soybean oil, cottonseed oil, sunflower seed oil, peanut oil, palm oil, corn oil, sesame oil, flaxseed oil, rice bran oil, tea oil, and olive oil.

7. The method for recovering mother liquor after purifying crude vitamin D3 or its metabolic derivatives according to claim 4, characterized in that, The high-boiling-point oil solution containing the oily concentrate is subjected to primary molecular distillation, with the distillation pressure controlled at 50-80 Pa, the feed flow rate at 10-20 g / min, and the molecular distillation scraper rotation speed at 150-200 rpm.

8. The method for recovering mother liquor after purifying crude vitamin D3 or its metabolic derivatives according to claim 4, characterized in that, The high-boiling-point oil solution containing the oily concentrate is subjected to primary molecular distillation, with the preheating temperature controlled at 45~60℃, the distillation temperature at 70~80℃, and the condensation temperature at 30~50℃.

9. The method for recovering mother liquor after purifying crude vitamin D3 or its metabolic derivatives according to claim 4, characterized in that, The heavy phase obtained from the primary molecular distillation product is subjected to a second molecular distillation, controlled according to the secondary molecular distillation method, with the distillation pressure controlled at 0~1 Pa and the molecular distillation scraper rotation speed at 200~280 rpm.

10. The method for recovering mother liquor after purifying crude vitamin D3 or its metabolic derivatives according to claim 4, characterized in that, The heavy phase obtained from the primary molecular distillation product is subjected to a second molecular distillation, controlled according to the two-stage molecular distillation method, with a preheating temperature of 50~70℃, a distillation temperature of 210~250℃, and a condensation temperature of 70~80℃.

11. The method for recovering mother liquor after purifying crude vitamin D3 or its metabolic derivatives according to claim 4, characterized in that, The heavy phase obtained from the first-stage molecular distillation product is subjected to a second molecular distillation, controlled according to the tertiary molecular distillation method, with a distillation pressure of 5~20 Pa and a molecular distillation scraper speed of 180~250 rpm.

12. The method for recovering mother liquor after purifying crude vitamin D3 or its metabolic derivatives according to claim 4, characterized in that, The heavy phase obtained from the first-stage molecular distillation product is subjected to a second molecular distillation, controlled according to the tertiary molecular distillation method, with a preheating temperature of 50~70℃, a distillation temperature of 170~200℃, and a condensation temperature of 70~80℃.

13. The method for recovering mother liquor after purifying crude vitamin D3 or its metabolic derivatives according to claim 4, characterized in that, The heavy phase obtained from the secondary molecular distillation product is subjected to a third molecular distillation, with the distillation pressure controlled at 0~1 Pa and the molecular distillation scraper rotation speed at 200~280 rpm.

14. The method for recovering mother liquor after purifying crude vitamin D3 or its metabolic derivatives according to claim 4, characterized in that, The heavy phase obtained from the secondary molecular distillation product is subjected to a third molecular distillation, with the preheating temperature controlled at 50-70℃, the distillation temperature at 210-250℃, and the condensation temperature at 70-80℃.