Method for preparing 24-dehydrocholesterol through separation of simulated moving bed chromatography

Abstract

The invention discloses a method for preparing 24-dehydrocholesterol through the separation of simulated moving bed chromatography. Crude 24-dehydrocholesterol which is extracted from lanolin is taken as a raw material; a stationary phase of the simulated moving bed chromatography is octadecylsilane chemically bonded silica with the particle size of 5 to 100mu m; and a mobile phase is an aqueous solution of methanol. A 24-dehydrocholesterol product with the purity of more than 98 percent is obtained by a simulated moving bed chromatography separation method; and the method is high in automation degree and efficiency, and is suitable for industrialized production, and the consumption of the stationary phase and a solvent are low.

Description

technical field

[0001] The invention relates to the field of processing and extraction of medicines, in particular to a method for separating and purifying 24-dehydrocholesterol by using simulated moving bed chromatography. Background technique

[0002] 24-Dehydrocholesterol (molecular structure such as formula I), also known as 3β-hydroxy-5,24-cholestadiene, chain sterol, is a white or near-white crystal or powder, insoluble in water, soluble in n-hexane, petroleum Ether and other non-polar solvents, easily soluble in more polar solvents such as alcohols.

[0003]

[0004] The molecular structure of 24-dehydrocholesterol and cholesterol is very similar. It not only has some physiological functions of cholesterol, but also is an important pharmaceutical intermediate. It has more advantages than cholesterol as the initial raw material for the synthesis of many physiologically active steroid compounds. Widely used in medicine, chemical industry, biochemistry and other fiel...

Examples

Embodiment 1

[0029] The simulated moving bed chromatography system is (Norr, Germany), equipped with 8 chromatographic columns (ID1×15cm), two in each zone, the stationary phase filled in the chromatographic columns is octadecylsilane bonded silica gel, the particle size is 50 μm, and the column temperature is 35°C. The mobile phase was anhydrous methanol. Crude 24-dehydrocholesterol, with a content of 89.2%, was prepared into a solution with anhydrous methanol at a concentration of 200 mg / mL.

[0030] A. Separation of weakly adsorbed impurity components, operating conditions:

[0031] Injection liquid flow rate: U P =1.0mL / min

[0032] Eluent flow rate: U E =6.0mL / min

[0033] Extraction liquid flow rate: U X =5.9mL / min

[0034] Raffinate flow rate: U R =1.1mL / min

[0035] Switching time: T s =180s

[0036] B. Separation of strongly adsorbed impurity components, operating conditions:

[0037] Injection liquid flow rate: U P =0.55mL / min

[0038] Eluent flow rate: U E =4.1mL...

Embodiment 2

[0045] Simulated Moving Bed Chromatography System (Norr, Germany) equipped with 24 chromatographic columns (ID1×15cm), 6 in each zone, the stationary phase filled in the chromatographic columns is octadecylsilane bonded silica gel, the particle size is 5 μm, and the column temperature is 15°C. The mobile phase was 70.0% methanol in water. Crude 24-dehydrocholesterol, content 85.0%, dissolved in 70.0% methanol aqueous solution, concentration 20mg / mL.

[0046] A. Separation of weakly adsorbed impurity components, operating conditions:

[0047] Injection liquid flow rate: U P =1.0mL / min

[0048] Eluent flow rate: U E =8.0mL / min

[0049] Extraction liquid flow rate: U X =7.5mL / min

[0050] Raffinate flow rate: U R =1.5mL / min

[0051] Switching time: T s =120s

[0052] B. Separation of strongly adsorbed impurity components, operating conditions:

[0053] Injection liquid flow rate: U P =1.0mL / min

[0054] Eluent flow rate: U E =12.0mL / min

[0055] Extraction liquid...

Embodiment 3

[0061] Simulated Moving Bed Chromatography System (Norr, Germany) equipped with 32 chromatographic columns (ID1×15cm), 8 in each zone, the stationary phase filled in the chromatographic columns is octadecylsilane bonded silica gel, the particle size is 20 μm and the column temperature is 50°C. The mobile phase was 96% methanol in water. Crude 24-dehydrocholesterol, content 80.1%, dissolved in 96.0% methanol aqueous solution, concentration 300mg / mL.

[0062] A. Separation of weakly adsorbed impurity components, operating conditions:

[0063] Injection liquid flow rate: U P =2.0mL / min

[0064] Eluent flow rate: U E =18.0mL / min

[0065] Extraction liquid flow rate: U X =16.0mL / min

[0066] Raffinate flow rate: U R =4.0mL / min

[0067] Switching time: T s =60s

[0068] B. Separation of strongly adsorbed impurity components, operating conditions:

[0069] Injection liquid flow rate: U P =1.2mL / min

[0070] Eluent flow rate: U E =9.0mL / min

[0071] Extraction liquid ...

technical field

[0001] The invention relates to the field of processing and extraction of medicines, in particular to a method for separating and purifying 24-dehydrocholesterol by using simulated moving bed chromatography. Background technique

[0002] 24-Dehydrocholesterol (molecular structure such as formula I), also known as 3β-hydroxy-5,24-cholestadiene, chain sterol, is a white or near-white crystal or powder, insoluble in water, soluble in n-hexane, petroleum Ether and other non-polar solvents, easily soluble in more polar solvents such as alcohols.

[0003]

[0004] The molecular structure of 24-dehydrocholesterol and cholesterol is very similar. It not only has some physiological functions of cholesterol, but also is an important pharmaceutical intermediate. It has more advantages than cholesterol as the initial raw material for the synthesis of many physiologically active steroid compounds. Widely used in medicine, chemical industry, biochemistry and other fiel...

Examples

Embodiment 1

[0029] The simulated moving bed chromatography system is (Norr, Germany), equipped with 8 chromatographic columns (ID1×15cm), two in each zone, the stationary phase filled in the chromatographic columns is octadecylsilane bonded silica gel, the particle size is 50 μm, and the column temperature is 35°C. The mobile phase was anhydrous methanol. Crude 24-dehydrocholesterol, with a content of 89.2%, was prepared into a solution with anhydrous methanol at a concentration of 200 mg / mL.

[0030] A. Separation of weakly adsorbed impurity components, operating conditions:

[0031] Injection liquid flow rate: U P =1.0mL / min

[0032] Eluent flow rate: U E =6.0mL / min

[0033] Extraction liquid flow rate: U X =5.9mL / min

[0034] Raffinate flow rate: U R =1.1mL / min

[0035] Switching time: T s =180s

[0036] B. Separation of strongly adsorbed impurity components, operating conditions:

[0037] Injection liquid flow rate: U P =0.55mL / min

[0038] Eluent flow rate: U E =4.1mL...

Embodiment 2

[0045] Simulated Moving Bed Chromatography System (Norr, Germany) equipped with 24 chromatographic columns (ID1×15cm), 6 in each zone, the stationary phase filled in the chromatographic columns is octadecylsilane bonded silica gel, the particle size is 5 μm, and the column temperature is 15°C. The mobile phase was 70.0% methanol in water. Crude 24-dehydrocholesterol, content 85.0%, dissolved in 70.0% methanol aqueous solution, concentration 20mg / mL.

[0046] A. Separation of weakly adsorbed impurity components, operating conditions:

[0047] Injection liquid flow rate: U P =1.0mL / min

[0048] Eluent flow rate: U E =8.0mL / min

[0049] Extraction liquid flow rate: U X =7.5mL / min

[0050] Raffinate flow rate: U R =1.5mL / min

[0051] Switching time: T s =120s

[0052] B. Separation of strongly adsorbed impurity components, operating conditions:

[0053] Injection liquid flow rate: U P =1.0mL / min

[0054] Eluent flow rate: U E =12.0mL / min

[0055] Extraction liquid...

Embodiment 3

[0061] Simulated Moving Bed Chromatography System (Norr, Germany) equipped with 32 chromatographic columns (ID1×15cm), 8 in each zone, the stationary phase filled in the chromatographic columns is octadecylsilane bonded silica gel, the particle size is 20 μm and the column temperature is 50°C. The mobile phase was 96% methanol in water. Crude 24-dehydrocholesterol, content 80.1%, dissolved in 96.0% methanol aqueous solution, concentration 300mg / mL.

[0062] A. Separation of weakly adsorbed impurity components, operating conditions:

[0063] Injection liquid flow rate: U P =2.0mL / min

[0064] Eluent flow rate: U E =18.0mL / min

[0065] Extraction liquid flow rate: U X =16.0mL / min

[0066] Raffinate flow rate: U R =4.0mL / min

[0067] Switching time: T s =60s

[0068] B. Separation of strongly adsorbed impurity components, operating conditions:

[0069] Injection liquid flow rate: U P =1.2mL / min

[0070] Eluent flow rate: U E =9.0mL / min

[0071] Extraction liquid ...

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