A preparation method of high-purity sodium nitroprusside raw material medicine

Abstract

The present invention provides a method for preparing a high-purity sodium nitroprusside raw material. Take the crude sodium nitroprusside and dissolve it in water at 50-60 °C, drop in anhydrous fatty alcohol, cool down to 20-25 °C, stir, add the supramolecular polymer TPAP-Mb@tQ[14], carry out ultrasonic oscillation, let it stand, perform high-speed centrifugal separation, filter, and collect the filtrate; carry out reduced-pressure distillation until no distillate is distilled out; add water, stir at 40-60 °C, cool to 10 °C and stir, filter, collect the filter cake, and dry it to obtain the first refined product of sodium nitroprusside. The provided preparation method has simple operation, great feasibility in industrial operation, less three-waste discharge, is green, environmentally friendly and sustainable, meets the requirements of industrial safe production, meets the requirements of industrial cost reduction and environmental protection, is conducive to large-scale industrial production, the purity of the prepared sodium nitroprusside is above 99%, up to 100% at most, and the yield is also above 85%, showing significant improvement compared with the prior art process and being more suitable for industrialization.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical synthesis, and specifically to a preparation method of a high-purity sodium nitroprusside raw material drug. Background Art

[0002] Sodium nitroprusside, molecular formula: C5H4FeN6Na2O3, molecular weight: 297.95, and the structural formula is as follows:

[0003]

[0004] Sodium nitroprusside (Sodium Nitroprusside Dihydrate), chemically named sodium nitroferricyanide dihydrate, is a strong vasodilator that directly acts on the arteriovenous vascular bed. This drug has a direct dilating effect on both resistance and capacitance vessels, and its effect on afterload is greater than that of nitroglycerin. Therefore, it can reduce the left ventricular filling pressure of patients and increase cardiac output. For the acute decompensation of patients with chronic left ventricular failure, sodium nitroprusside is more effective and faster than furosemide. Its mechanism of action is the same as that of nitrates, which can cause vascular endothelial cells to release NO and activate guanylate cyclase, increasing the intracellular cGMP level and dilating blood vessels. Clinically, the specific types of hemodynamic changes and the underlying pathological basis may help in the selection of drugs. For patients with obvious pump dysfunction, increased left ventricular filling pressure and significantly increased peripheral vascular resistance, with reduced cardiac output and normal or increased arterial pressure, it is advisable to use sodium nitroprusside for short-term intravenous infusion. The half-life of sodium nitroprusside is extremely short. Its action duration is only 5 - 15 minutes, so intravenous infusion should be used to maintain the efficacy. It is first converted into cyanide by red blood cells, and then into the final metabolite thiocyanate by rhodanase in the liver. Thiocyanate is excreted by the kidneys, and the half-life in patients with normal renal function is 4 - 7 days. In patients with renal failure, there is accumulation. If the dose is too large, the metabolite thiocyanate in the blood is too high and poisoning is likely to occur.

[0005] In order to ensure the safety of clinical medication, the pharmacopoeia has limited the content of sodium nitroprusside. The "Chinese Pharmacopoeia (2020 Edition)" stipulates that calculated on the dried product, the content of Na2Fe(CN)5NO shall not be less than 99.0%; in addition, the pharmacopoeia has also limited the contents of impurities such as chlorides, ferricyanides, ferrocyanides, and insoluble substances in water in sodium nitroprusside. However, the methods in the existing published literature have the following problems:

[0006] 1) The raw material contains potassium ferricyanide:

[0007] It is easily decomposed into highly toxic cyanides such as potassium cyanide and HCN at high temperatures. Its aqueous solution is easily decomposed by light or the action of alkali to produce highly toxic cyanides such as potassium cyanide and HCN. As a highly toxic substance, potassium cyanide can cause serious harm to most organisms including humans even at very low concentrations, thus bringing great potential safety hazards to production. In addition, the prepared product often contains excessive potassium ferrocyanide and other ferrocyanides and ferricyanides as by-products or impurities, which are difficult to remove and affect the medicinal safety of the product.

[0008] 2) The raw material contains sodium nitroprusside:

[0009] The raw material sodium nitroprusside is extremely difficult to obtain. Generally, only reagent-grade products are available on the market and they are very expensive. There are problems with the source of materials, making it unsuitable for industrial-scale production and commercialization.

[0010] 3) The raw material contains copper salts:

[0011] Using copper salts such as copper sulfate as reaction raw materials introduces heavy metal ions copper into the reaction, which may be difficult to completely remove, resulting in excessive heavy metal copper in the product. If it enters the body directly through intravenous injection, there are risks in drug use, making it unsuitable for industrial-scale production and commercialization.

[0012] 4) The raw material contains sodium nitrite:

[0013] Using sodium nitrite as a reaction raw material produces toxic gases such as NO and (CN)2 during the reaction process.

[0014] 5) A large amount of inorganic salt impurities are accompanied in the product:

[0015] A large amount of inorganic salt impurities such as potassium nitrate, ammonium nitrate, and sodium nitrate are accompanied in the product, which are difficult to remove, resulting in extremely low purity of the final product.

[0016] Therefore, it is necessary to develop a new preparation method for sodium nitroprusside to solve the above problems existing in the sodium nitroprusside prepared by the prior art. Summary of the Invention

[0017] Aiming at the deficiencies in the prior art, the purpose of the present invention is to provide a preparation method for high-purity sodium nitroprusside raw material medicine to solve the problems existing in the existing preparation methods for sodium nitroprusside raw material medicine.

[0018] The technical solution of the present invention is as follows:

[0019] The first aspect of the present invention provides a preparation method for high-purity sodium nitroprusside raw material medicine, specifically including the following reaction formula and reaction steps:

[0020]

[0021] 1) Dissolve the crude sodium nitroprusside in water at 50 - 60 °C, drop in anhydrous fatty alcohol, cool down to 20 - 25 °C, stir, add the supramolecular polymer TPAP-Mb@tQ

[14] , conduct ultrasonic oscillation, let it stand, separate by high-speed centrifugation, filter, and collect the filtrate;

[0022] 2) Conduct vacuum distillation until no distillate is distilled out;

[0023] 3) Add water, stir at 40 - 60 °C, cool to 10 °C and stir, filter, collect the filter cake, dry, and obtain the first refined product of sodium nitroprusside;

[0024] According to the above preparation method of high-purity sodium nitroprusside raw material drug, the fatty alcohol is preferably one or a mixture of several of C1 - C8 fatty alcohols, more preferably one or a mixture of several of monohydric alcohols, dihydric alcohols or trihydric alcohols in C1 - C8 fatty alcohols, still more preferably one or a mixture of several of monohydric alcohols, dihydric alcohols or trihydric alcohols in C1 - C8 straight-chain fatty alcohols, particularly preferably one or a mixture of several of methanol, ethanol, propanol, n-butanol, tert-butanol, n-pentanol, n-hexanol, isopropanol, 2-methyl-1-propanol, n-butanol, 2-methyl-2-propanol, ethylene glycol, glycerol, propylene glycol, and most preferably one or a mixture of several of methanol, ethanol, propanol, isopropanol, n-butanol, tert-butanol, 2-methyl-2-propanol, particularly preferably one or a mixture of several of methanol, ethanol, propanol, isopropanol, still particularly preferably one or two of methanol, ethanol, propanol, isopropanol, and most preferably ethanol;

[0025] According to the above preparation method of high-purity sodium nitroprusside raw material drug, the supramolecular polymer TPAP-Mb@tQ

[14] can be constructed by the host-guest interaction of triphenylamine derivative TPAP-Mb and macrocyclic compound helical 14-membered cucurbituril tQ

[14] ; the triphenylamine derivative TPAP-Mb is

[0026] 1,1’,1”-(((nitrilotris(benzene-4,1-diyl))-tris(pyridine-1-ium-4,1-diyl))tris(butane-4,1-diyl))tris(4-meth-ylpyridine-1-ium);

[0027] According to the above preparation method of high-purity sodium nitroprusside raw material drug, the water can be tap water, deionized water, distilled water or purified water, preferably purified water;

[0028] According to the above preparation method of high-purity sodium nitroprusside raw material, the feeding ratio (kg / kg) of crude sodium nitroprusside to water is preferably 1:(1.0 - 4.0), more preferably 1:(1.5 - 3.5), still more preferably 1:(2.0 - 3.0), and most preferably 1:2.5; in the above preparation method, the feeding ratio for the two water additions in steps 1) and 3) is this ratio respectively;

[0029] According to the above preparation method of high-purity sodium nitroprusside raw material, the feeding ratio (kg / kg) of crude sodium nitroprusside to anhydrous fatty alcohol is preferably 1:(3.0 - 5.0), more preferably 1:(3.5 - 4.5), still more preferably 1:(3.2 - 4.2), and most preferably 1:3.9;

[0030] According to the above preparation method of high-purity sodium nitroprusside raw material, the feeding ratio (kg / kg) of crude sodium nitroprusside to supramolecular polymer TPAP-Mb@tQ

[14] is preferably 1:(0.1 - 1), more preferably 1:(0.1 - 0.5), still more preferably 1:(0.1 - 0.25), and most preferably 1:0.25;

[0031] According to the above preparation method of high-purity sodium nitroprusside raw material, the stirring time after cooling to 20 - 25°C in step 1) is preferably 1 - 3 h, more preferably 1 - 2.5 h, and most preferably 1 - 2 h;

[0032] According to the above preparation method of high-purity sodium nitroprusside raw material, the ultrasonic oscillation time after adding the supramolecular polymer in step 1) is preferably 1 - 3 h, more preferably 1 - 2.5 h, and most preferably 1 - 2 h;

[0033] According to the above preparation method of high-purity sodium nitroprusside raw material, the standing time after ultrasonic oscillation in step 1) is preferably 1 - 3 h, more preferably 1 - 2 h, still more preferably 1 - 1.5 h, and most preferably 1 h;

[0034] According to the above preparation method of high-purity sodium nitroprusside raw material, the temperature of vacuum distillation in step 2) is preferably 40 - 100°C, more preferably 40 - 90°C, still more preferably 40 - 80°C, particularly preferably 40 - 70°C, especially preferably 40 - 65°C, and most preferably 40 - 60°C;

[0035] According to the above preparation method of high-purity sodium nitroprusside raw material, the stirring time at 40 - 60°C in step 3) is preferably 1 - 3 h, more preferably 1 - 2 h, still more preferably 1 - 1.5 h, and most preferably 1 h;

[0036] According to the above preparation method of high-purity sodium nitroprusside raw material, the stirring time at 10°C in step 3) is preferably 1 - 3 h, more preferably 1 - 2 h, still more preferably 1 - 1.5 h, and most preferably 1 h;

[0037] According to the above preparation method of high-purity sodium nitroprusside raw material, the drying temperature in step 3) is preferably 40 - 100°C, more preferably 40 - 90°C, still more preferably 50 - 80°C, particularly preferably 50 - 70°C, especially preferably 50 - 65°C, and most preferably 50 - 60°C.

[0038] According to the above preparation method of high-purity sodium nitroprusside raw material, the filter residue obtained by filtering in step 1) can be dissolved in a mixed solution of acetone and chloroform to recover the macrocyclic compound helical cucurbit

[14] uril tQ

[14] ;

[0039] According to the above preparation method of high-purity sodium nitroprusside raw material, the feeding ratio of acetone to chloroform is preferably 1:1;

[0040] Furthermore, the above preparation method of high-purity sodium nitroprusside raw material may further include the following reaction formula and reaction steps:

[0041]

[0042] 1) Dissolve the prepared sodium nitroprusside solid and water by stirring at 40 - 50°C, cool to 30°C and stir, filter, and collect the filtrate;

[0043] 2) Distill off part of the water under reduced pressure, cool to 20°C and stir, filter, and collect the filter cake;

[0044] 3) Stir the filter cake and water at 50 - 60°C, cool to 20°C and stir, filter, and dry to obtain the second refined product of sodium nitroprusside;

[0045] According to the above preparation method of high-purity sodium nitroprusside raw material, the water can be tap water, deionized water, distilled water or purified water, preferably purified water;

[0046] According to the above preparation method of high-purity sodium nitroprusside raw material, the feeding ratio of sodium nitroprusside solid to water for dissolution (kg / kg) is preferably 1:(1.0 - 4.0), more preferably 1:(1.5 - 3.5), still more preferably 1:(1.0 - 3.0), and most preferably 1:2.0;

[0047] According to the above preparation method of high-purity sodium nitroprusside raw material, the feeding ratio of sodium nitroprusside solid to water for stirring (kg / kg) is preferably 1:(0.1 - 0.6), more preferably 1:(0.2 - 0.5), still more preferably 1:(0.27 - 0.39), and most preferably 1:0.32;

[0048] According to the above-mentioned preparation method of high-purity sodium nitroprusside raw material, the stirring time at the temperature reduced to 30°C in step 1) is preferably 1 - 3 h, more preferably 1 - 2 h, still more preferably 1 - 1.5 h, and most preferably 1 h;

[0049] According to the above-mentioned preparation method of high-purity sodium nitroprusside raw material, the temperature of vacuum distillation in step 2) is preferably 40 - 100°C, more preferably 40 - 90°C, still more preferably 50 - 80°C, particularly preferably 50 - 70°C, especially preferably 50 - 65°C, and most preferably 50 - 60°C;

[0050] According to the above-mentioned preparation method of high-purity sodium nitroprusside raw material, the stirring time at the temperature cooled to 20°C in step 2) is preferably 1 - 3 h, more preferably 1 - 2 h, still more preferably 1 - 1.5 h, and most preferably 1 h;

[0051] According to the above-mentioned preparation method of high-purity sodium nitroprusside raw material, the stirring time at 50 - 60°C in step 3) is preferably 1 - 3 h, more preferably 1 - 2 h, still more preferably 1 - 1.5 h, and most preferably 1 h;

[0052] According to the above-mentioned preparation method of high-purity sodium nitroprusside raw material, the stirring time at the temperature cooled to 20°C in step 3) is preferably 1 - 3 h, more preferably 1 - 2 h, still more preferably 1 - 1.5 h, and most preferably 1 h;

[0053] According to the above-mentioned preparation method of high-purity sodium nitroprusside raw material, the drying temperature in step 3) is preferably 40 - 100°C, more preferably 40 - 90°C, still more preferably 50 - 80°C, particularly preferably 50 - 70°C, especially preferably 50 - 65°C, and most preferably 50 - 60°C.

[0054] The second aspect of the present invention provides a pharmaceutical composition, which comprises a therapeutically and / or prophylactically effective amount of a drug active ingredient selected from sodium nitroprusside prepared according to any of the above preparation methods, and at least one pharmaceutically acceptable carrier or adjuvant.

[0055] The third aspect of the present invention provides the use of sodium nitroprusside prepared according to any of the above preparation methods in the preparation of a drug for treating and / or preventing vasodilation.

[0056] The preparation method of the high-purity sodium nitroprusside raw material provided by the present invention has the following beneficial effects:

[0057] 1) Compared with the known preparation methods, the preparation method provided by the present invention is simple in operation, has great feasibility in industrial operation, less discharge of three wastes, is green, environmentally friendly and sustainable, meets the requirements of industrial safe production, meets the requirements of industrial cost reduction and environmental protection, is conducive to large-scale industrial production, the purity of the prepared sodium nitroprusside is above 99%, up to 100% at most, and the yield is also above 85%, showing significant improvement and enhancement compared with the prior art processes, and is more suitable for industrialization;

[0058] 2) Compared with the known preparation methods, the sodium nitroprusside prepared by the preparation method provided by the present invention not only has a purity above 99%, but also controls the contents of impurities such as ferrocyanide, ferricyanide, potassium nitrate, ammonium nitrate, sodium nitrate, chloride, etc. and the water-insoluble substances within the limits of the quality standards, ensuring the efficacy and safety of clinical medications. Brief Description of the Drawings

[0059] Figure 1 It is the HPLC chromatogram of the first refined product of the sodium nitroprusside prepared in Example 1 of the present invention;

[0060] Figure 2 It is the HPLC chromatogram of the second refined product of the sodium nitroprusside prepared in Example 1 of the present invention;

[0061] Figure 3 It is the HPLC chromatogram of the first refined product of the sodium nitroprusside prepared in Example 2 of the present invention;

[0062] Figure 4 It is the HPLC chromatogram of the second refined product of the sodium nitroprusside prepared in Example 2 of the present invention;

[0063] Figure 5 It is the HPLC chromatogram of the first refined product of the sodium nitroprusside prepared in Example 3 of the present invention;

[0064] Figure 6 It is the HPLC chromatogram of the second refined product of the sodium nitroprusside prepared in Example 3 of the present invention;

[0065] Figure 7 It is the HPLC chromatogram of the first refined product of the sodium nitroprusside prepared in Comparative Example 2 of the present invention;

[0066] Figure 8 It is the HPLC chromatogram of the second refined product of the sodium nitroprusside prepared in Comparative Example 2 of the present invention; Detailed Embodiments

[0067] In order to make the objectives, technical solutions and advantages of the present invention more clearly understood, the present invention will be further described in detail below in conjunction with embodiments and the accompanying drawings. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0068] In the examples and comparative examples, the temperature is room temperature unless otherwise specified.

[0069] In the examples and comparative examples, the proportion of components in the mixed solvent is the volume ratio unless otherwise specified.

[0070] The reaction solvents and reaction reagents mentioned in the following examples and comparative examples can be directly purchased from the market.

[0071] The supramolecular polymer TPAP-Mb@tQ

[14] mentioned in the following examples and comparative examples can be directly purchased from the market or prepared according to the methods disclosed in the prior art.

[0072] In the following examples and comparative examples of the present invention, the crude sodium nitroprusside as the starting material can be prepared by the method provided in Comparative Example 1 of the present invention, can be directly purchased from the market, or can be prepared according to the methods known in the art.

[0073] Example 1 Preparation of High-Purity Sodium Nitroprusside

[0074] (1) First Refinement of Sodium Nitroprusside

[0075]

[0076] 1) 1.0 kg of crude sodium nitroprusside was stirred and dissolved with 2.5 kg of water at 50 °C, 3.95 kg of absolute ethanol was added dropwise. After the addition, the temperature was lowered to 20 °C, stirred for 1 h, 0.15 kg of supramolecular polymer TPAP-Mb@tQ

[14] was added, ultrasonic oscillation was carried out for 2 h, allowed to stand for 1 h, separated by high-speed centrifugation, filtered, and the filtrate was collected.

[0077] 2) Distillation under reduced pressure at 40 °C until no distillate was distilled out.

[0078] 3) 0.25 kg of water was added, stirred at 40 °C for 1 h; cooled to 10 °C and stirred for 1 h, filtered, and the filter cake was dried in vacuo at 50 °C to obtain the first refined product, with a yield of 91.6% and a purity of 99.03%.

[0079] (2) Second Refinement of Sodium Nitroprusside

[0080]

[0081] 1) 1.0 kg of the first refined product of sodium nitroprusside was stirred and dissolved with 2.0 kg of water at 40 °C, the temperature was lowered to 30 °C and stirred for 1 h, filtered, and the filtrate was collected.

[0082] 2) Distill off part of the water under reduced pressure at 50 °C, cool to 20 °C, stir for 1 h, and filter;

[0083] 3) Stir the filter cake with 0.32 kg of water at 50 °C for 1 h; cool to 20 °C and stir for 1 h, filter, and dry under vacuum at 50 °C to obtain the second refined product of sodium nitroprusside, with a yield of 88.5% and a purity of 100%.

[0084] Example 2 Preparation of High-Purity Sodium Nitroprusside

[0085] (1) First Refinement of Sodium Nitroprusside

[0086]

[0087] 1) Dissolve 1.0 kg of crude sodium nitroprusside in 2.0 kg of water by stirring at 55 °C, drop in 3.95 kg of absolute ethanol, after dropping, cool to 55 °C, stir for 1.2 h, add 0.1 kg of supramolecular polymer TPAP-Mb@tQ

[14] , ultrasonically oscillate for 1.5 h, stand for 1 h, centrifuge at high speed for separation, filter, and collect the filtrate;

[0088] 2) Distill under reduced pressure at 50 °C until no more distillate is distilled off;

[0089] 3) Add 0.21 kg of water, stir at 50 °C for 1 h; cool to 10 °C and stir for 1 h, filter, and dry the filter cake under vacuum at 55 °C to obtain the first refined product, with a yield of 90.3% and a purity of 98.45%.

[0090] (2) Second Refinement of Sodium Nitroprusside

[0091]

[0092] 1) Dissolve 1.0 kg of the first refined product of sodium nitroprusside in 2.0 kg of water by stirring at 45 °C, cool to 30 °C and stir for 1 h, filter, and collect the filtrate;

[0093] 2) Distill off part of the water under reduced pressure at 55 °C, cool to 20 °C, stir for 1 h, and filter;

[0094] 3) Stir the filter cake with 0.27 kg of water at 55 °C for 1 h; cool to 20 °C and stir for 1 h, filter, and dry under vacuum at 55 °C to obtain the second refined product of sodium nitroprusside, with a yield of 87.2% and a purity of 99.88%.

[0095] Example 3 Preparation of High-Purity Sodium Nitroprusside

[0096] (1) First Refinement of Sodium Nitroprusside

[0097]

[0098] 1) Dissolve 1.0 kg of crude sodium nitroprusside in 3.0 kg of water with stirring at 60 °C. Drop in 3.95 kg of absolute ethanol. After dropping, cool the temperature to 25 °C, stir for 2 h, add 0.25 kg of supramolecular polymer TPAP-Mb@tQ

[14] , ultrasonically vibrate for 1 h, let stand for 1 h, separate by high-speed centrifugation, filter, and collect the filtrate;

[0099] 2) Distill under reduced pressure at 60 °C until no more distillate is distilled out;

[0100] 3) Add 0.30 kg of water, stir at 60 °C for 1 h; cool to 10 °C and stir for 1 h, filter, and vacuum dry the filter cake at 60 °C to obtain the first refined product with a yield of 93.4% and a purity of 98.60%.

[0101] (2) Second refinement of sodium nitroprusside

[0102]

[0103] 1) Dissolve 1.0 kg of the first refined product of sodium nitroprusside in 2.0 kg of water with stirring at 50 °C. Cool the temperature to 30 °C and stir for 1 h, filter, and collect the filtrate;

[0104] 2) Distill off part of the water under reduced pressure at 60 °C, cool to 20 °C and stir for 1 h, filter;

[0105] 3) Stir the filter cake with 0.39 kg of water at 60 °C for 1 h; cool to 20 °C and stir for 1 h, filter, and vacuum dry at 60 °C to obtain the second refined product of sodium nitroprusside with a yield of 89.3% and a purity of 100%.

[0106] Preparation of sodium nitroprusside raw material drug in Comparative Example 1

[0107]

[0108] 1) Mix 42.2 kg of potassium ferrocyanide and 84 L of water and stir, with a water bath at 17 °C;

[0109] 2) Rapidly drop 48.5 kg of concentrated nitric acid with a concentration of 65%, finish dropping in about 5 minutes, and the temperature rises to 27 °C to obtain a yellow emulsion;

[0110] 3) Heat in a water bath to 60 °C, a large number of bubbles are generated, and the temperature soars by 10 °C; the solution becomes clear and turns into a reddish-brown solution, and the bubbles stop;

[0111] 4) Heat to 90 °C and stir, and bubbles are generated again. After 15 minutes, the bubbles stop, and stir for 1 h to obtain a dark green solution;

[0112] 5) Concentrate out 50 L of water, cool to 5 °C and stir for 40 minutes, filter, with a slow speed, to obtain a dark green filtrate;

[0113] 6) Adjust the pH value to 7 - 8 with 10.6 kg of 15% sodium carbonate solution, stir in a water bath at 90 °C for 1 h to obtain a reddish-brown solution; cool to room temperature and filter to remove insoluble substances;

[0114] 7) Concentrate the filtrate until crystallization occurs, cool to 5 °C and stir for 1 h, filter and dry to obtain 9.44 kg of light red powder, with a yield of 31.7% and a purity of 53.2%.

[0115] Preparation of Sodium Nitroprusside API for Comparative Example 2

[0116] (1) First Refinement of Sodium Nitroprusside

[0117]

[0118] 1) Dissolve 1.0 kg of crude sodium nitroprusside in 2.5 kg of water with stirring at 50 °C, cool to 20 °C, add 0.15 kg of supramolecular polymer TPAP-Mb@tQ

[14] , ultrasonically vibrate for 2 h, let stand for 1 h, separate by high-speed centrifugation, filter, and collect the filtrate;

[0119] 2) Distill under reduced pressure at 40 °C until no more distillate is obtained;

[0120] 3) Add 0.25 kg of water, stir at 40 °C for 1 h; cool to 10 °C and stir for 1 h, filter, and vacuum dry the filter cake at 50 °C to obtain the first refined product, with a yield of 90.3% and a purity of 84.16%.

[0121] (2) Second Refinement of Sodium Nitroprusside

[0122]

[0123] 1) Dissolve 1.0 kg of the first refined product of sodium nitroprusside in 2.0 kg of water with stirring at 40 °C, cool to 30 °C and stir for 1 h, filter, and collect the filtrate;

[0124] 2) Distill off some water under reduced pressure at 50 °C, cool to 20 °C and stir for 1 h, filter;

[0125] 3) Stir the filter cake with 0.32 kg of water at 50 °C for 1 h; cool to 20 °C and stir for 1 h, filter, and vacuum dry at 50 °C to obtain the second refined product of sodium nitroprusside, with a yield of 86.9% and a purity of 87.67%.

[0126] Detection Example 1 Detection Test for Residual Ferricyanide and Ferrocyanide

[0127] Take the sodium nitroprusside APIs prepared in Examples 1 - 3 and Comparative Example 1 and conduct the following inspections according to the inspection methods described in the relevant sections of "Chinese Pharmacopoeia (2020 Edition), Volume II, First Part of Monographs, Sodium Nitroprusside":

[0128] (1) Detection of Ferricyanide Residue

[0129] Respectively take 0.50 g of the sodium nitroprusside bulk drugs prepared in Examples 1 - 3 and Comparative Examples 1 - 2. After dissolving in 10 ml of water, add 1 ml of ferrous sulfate test solution, observe the test phenomena and record them in the following table:

[0130]

[0131] Conclusion:

[0132] It can be seen from the test results that the residues of ferricyanide in the sodium nitroprusside bulk drugs prepared in Examples 1 - 3 of the present invention all meet the requirements of the Chinese Pharmacopoeia (2020 Edition), and the residue of ferricyanide in the sodium nitroprusside bulk drug prepared in Comparative Example 1 exceeds the content specified in the Chinese Pharmacopoeia (2020 Edition).

[0133] (2) Detection of Ferrocyanide Residue

[0134] Respectively take 1.0 g of the sodium nitroprusside bulk drugs prepared in Examples 1 - 3 and Comparative Example 1. After dissolving in 20 ml of water, divide them into two equal parts: add 0.05 ml of ferric chloride test solution to one part, shake well, compare with the other part, observe the test phenomena and record them in the following table:

[0135]

[0136] Conclusion:

[0137] It can be seen from the test results that the residues of ferrocyanide in the sodium nitroprusside bulk drugs prepared in Examples 1 - 3 of the present invention all meet the requirements of the Chinese Pharmacopoeia (2020 Edition), and the residue of ferrocyanide in the sodium nitroprusside bulk drug prepared in Comparative Example 1 exceeds the content specified in the Chinese Pharmacopoeia (2020 Edition).

[0138] All patent documents and non - patent publications cited in this specification are hereby incorporated by reference in their entirety.

[0139] Unless otherwise stated, the percentages stated throughout the specification of this application are weight / weight (w / w) percentages.

[0140] The description of the above embodiments is only used to help understand the method and its core idea of the present invention. It should be noted that for those of ordinary skill in the art of this technology, without departing from the principle of the present invention, several improvements and modifications can be made to the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention.

Claims

1. A preparation method of high-purity sodium nitroprusside raw material drug, characterized in that, The preparation method includes a first purification and a second purification; wherein the first purification includes the following steps: 1) Take the crude sodium nitroprusside and dissolve it in water at 50 - 60 °C. Drop in anhydrous fatty alcohol, cool down to 20 - 25 °C, stir, add the supramolecular polymer TPAP-Mb@tQ[14], perform ultrasonic oscillation, let it stand, separate by high-speed centrifugation, filter, and collect the filtrate; 2) Perform vacuum distillation until no more distillate is distilled out; 3) Add water, stir at 40 - 60 °C, cool to 10 °C and stir, filter, collect the filter cake, and dry to obtain the first refined product of sodium nitroprusside; The fatty alcohol is one of methanol, ethanol, propanol, tert-butanol, and isopropanol; The water is tap water, deionized water, distilled water, or purified water; The mass feeding ratio of the crude sodium nitroprusside to water is 1:(1.0 - 4.0); The mass feeding ratio of the crude sodium nitroprusside to anhydrous fatty alcohol is 1:(3.0 - 5.0); The mass feeding ratio of the crude sodium nitroprusside to the supramolecular polymer TPAP-Mb@tQ[14] is 1:(0.1 - 1); The second purification includes the following steps: 1) Stir and dissolve the solid of the first refined product of sodium nitroprusside obtained and water at 40 - 50 °C, cool to 30 °C and stir, filter, and collect the filtrate; 2) Vacuum distill a part of the water, cool to 20 °C and stir, filter, and collect the filter cake; 3) Stir the filter cake and water at 50 - 60 °C, cool to 20 °C and stir, filter, and dry to obtain the second refined product of sodium nitroprusside.

2. The preparation method according to claim 1, wherein The fatty alcohol in the first purification is ethanol.

3. The preparation method according to claim 1, characterized in that, In step 1) of the first purification, the stirring time after cooling to 20 - 25 °C is 1 - 3 h.

4. The preparation method according to claim 1, characterized in that, In step 1) of the first purification, the ultrasonic oscillation time after adding the supramolecular polymer is 1 - 3 h, and the standing time after ultrasonic oscillation is 1 - 3 h.

5. The preparation method according to claim 1, characterized in that, In step 2) of the first purification, the temperature of vacuum distillation is 40 - 100 °C.

6. The preparation method according to claim 1, characterized in that, In step 3) of the first purification, the stirring time at 40 - 60 °C is 1 - 3 h; in step 3) of the first purification, the stirring time when cooling to 10 °C is 1 - 3 h; in step 3) of the first purification, the drying temperature is 40 - 100 °C.

7. The preparation method according to claim 1, characterized in that, The water in the second purification is deionized water, distilled water, or purified water; in step 1) of the second purification, the mass feeding ratio of the solid of the first refined product of sodium nitroprusside to the water for dissolution is 1:(1.0 - 4.0).

8. The preparation method according to claim 1, characterized in that, In step 1) of the second purification, the stirring time when cooling to 30 °C is 1 - 3 h.

9. The preparation method according to claim 1, characterized in that, In step 2) of the second purification, the temperature of vacuum distillation is 40 - 100 °C; in step 2) of the second purification, the stirring time when cooling to 20 °C is 1 - 3 h.

10. The preparation method according to claim 1, characterized in that, In step 3) of the second purification, the stirring time at 50 - 60 °C is 1 - 3 h; in step 3) of the second purification, the stirring time when cooling to 20 °C is 1 - 3 h; in step 3) of the second purification, the drying temperature is 40 - 100 °C.

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