Method for converting sophocarpidine in radix sophorae flavescentis percolate into sophocarpidine

Abstract

The invention belongs to the technical field of matrine preparation, and particularly relates to a method for converting sophocarpine in radix sophorae flavescentis percolate into matrine. Comprising the following steps: adding Na2SO3 into the radix sophorae flavescentis percolate, reacting at the temperature of 20-25 DEG C, namely near room temperature, and converting sophocarpine in the radix sophorae flavescentis percolate into sophocarpine; the mass volume ratio of the Na2SO3 to the radix sophorae flavescentis percolate solution is (0.022 g to 0.024 g): 1 mL. According to the method, efficient conversion of sophocarpine into sophocarpidine can be achieved by accurately controlling the adding amount of Na2SO3, the whole conversion process is mild, a catalyst and a high-temperature environment do not need to be added, and the efficiency of converting sophocarpidine into sophocarpidine is effectively improved.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of matrine preparation, and particularly relates to a method for converting sophocarpine in sophora flavescens percolation liquid into matrine. BACKGROUND

[0002] Matrine alkaloids are represented by matrine and have a skeleton structure, i.e., belong to double-fused piperidine alkaloids. This kind of matrine includes matrine (MT), oxymatrine (OMT), sophocarpine (SC), sorphoridine (SRI), oxysophocarpine (OSC), and oxysophoridine (OSRI). Matrine alkaloids are widely sourced from leguminous plants such as sophora flavescens, sophora alopecuroides, and isopycroides, and in recent years, a large number of pharmacological and clinical studies on matrine and oxymatrine have found that they have anti-inflammatory, antiviral, liver-protecting, antitumor effects, and central nervous system sedative, analgesic, antipyretic, cooling effects, and various pharmacological effects such as cardiotonic, antihypertensive, and antiarrhythmic effects, and are widely used in daily necessities, pesticides, and veterinary drugs. A large number of studies in recent years have shown that total alkaloids or monomer alkaloids have many biological activities, and vigorously developing and promoting the clinical use of sophora alopecuroides alkaloids has great economic and social value.

[0003] In order to better treat diseases in multiple ways, it is necessary to comprehensively and systematically study sophora flavescens alkaloids. Great progress has been made in recent years, but the clinical application needs to be further developed. In order to improve the pharmacological activity and clinical effect of matrine alkaloids, realize the effective conversion between sophora flavescens alkaloids, meet the demand for some monomer alkaloids, and seek effective conversion paths between various sophora flavescens alkaloids, so as to reduce costs, simplify process flow, and realize industrial production. At present, matrine is prepared from sophocarpine by transfer hydrogenation, by adding a catalyst such as a nickel, palladium, platinum, or other metal catalyst, and the commonly used catalyst is Raney nickel catalyst, which is easy to deactivate and affects the conversion rate, and pollutes the environment. As can be seen, the existing processes for converting sophocarpine into matrine all need to use a catalyst, and the catalyst has the problems of easy deactivation, reduced conversion rate, and environmental pollution. SUMMARY

[0004] In order to solve the above problems, the application provides a method for converting sophocarpine in sophora flavescens percolation liquid into matrine.

[0005] The technical scheme of the application is as follows.

[0006] A method for converting sophocarpine in sophora flavescens percolation liquid into matrine, comprising the following steps: The Na2SO3 is added to the Sophora flavescens percolation liquid, and a reduction reaction is performed at 20-25°C to convert sophoridine in the Sophora flavescens percolation liquid into matrine; the reaction condition is mild at 20-25°C close to room temperature; The mass-volume ratio of the Na2SO3 to the Sophora flavescens percolation liquid solution is 22-24 mg: 1 mL. When the Na2SO3 addition amount is greater than 22 mg / mL, the conversion rate tends to be stable, and when the Na2SO3 addition amount reaches 24 mg / mL, the conversion rate is the largest, and the entire conversion process can be ensured without adding any catalyst.

[0007] In another preferred embodiment, the mass-volume ratio of the Na2SO3 to the Sophora flavescens percolation liquid solution is 0.024 g: 1 mL; the reaction time is 2-3 h, preferably, the reaction time is 2.5 h, and if the reaction time is further increased, by-products will be produced, affecting the conversion result.

[0008] In another preferred embodiment, the Sophora flavescens percolation liquid is obtained by the following specific process: The Sophora flavescens soaked with the alcohol reagent is taken out and soaked in the alcohol reagent again, and after air removal and compaction, percolation treatment is performed to obtain the Sophora flavescens percolation liquid; The outflow speed of the Sophora flavescens percolation liquid is 2-3 mL / min.

[0009] In another preferred embodiment, the soaking time is 20-24 h.

[0010] In another preferred embodiment, the alcohol reagent is 60-90% ethanol by mass percentage. The use of the ethanol with the mass percentage can make the crude base yield in the Sophora flavescens percolation liquid higher, which is beneficial to subsequent reduction.

[0011] In another preferred embodiment, the pH value of the Sophora flavescens percolation liquid is 2-4, which improves the content of sophoridine and matrine in the Sophora flavescens percolation liquid.

[0012] In another preferred embodiment, the Sophora flavescens is Sophora flavescens particles with a particle size of 0.5 cm.

[0013] In another preferred embodiment, the Sophora flavescens percolation liquid further includes heating to remove the alcohol reagent before the Na2SO3 is added.

[0014] In another preferred embodiment, the compaction is performed by using glass beads.

[0015] Compared with the prior art, the present application has the following beneficial effects: The application controls the adding amount of Na2SO3 precisely, under the condition that the mass-volume ratio of Na2SO3 and Sophora flavescens percolation solution is 0.022g-0.024g:1mL, the strong reducing property of S in Na2SO3 is used to effectively improve the conversion rate of sophoridine to convert matrine to more than 98%. And the whole conversion process is mild, which can be carried out at 20-25 DEG C, close to room temperature, and no catalyst is needed in the whole reaction process. 4+ The application controls the adding amount of Na2SO3 precisely, under the condition that the mass-volume ratio of Na2SO3 and Sophora flavescens percolation solution is 0.022g-0.024g:1mL, the strong reducing property of S in Na2SO3 is used to effectively improve the conversion rate of sophoridine to convert matrine to more than 98%. And the whole conversion process is mild, which can be carried out at 20-25 DEG C, close to room temperature, and no catalyst is needed in the whole reaction process.

[0016] The application controls the adding amount of Na2SO3 precisely, under the condition that the mass-volume ratio of Na2SO3 and Sophora flavescens percolation solution is 0.022g-0.024g:1mL, the strong reducing property of S in Na2SO3 is used to effectively improve the conversion rate of sophoridine to convert matrine to more than 98%. And the whole conversion process is mild, which can be carried out at 20-25 DEG C, close to room temperature, and no catalyst is needed in the whole reaction process. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 It is the result graph of reducing sophoridine to matrine.

[0018] Figure 2 It is the result graph of reducing sophoridine to matrine.

[0019] Figure 3 It is the result graph of the repeated experiment of the application. Figure 2 It is the result graph of the repeated experiment of the application. DETAILED DESCRIPTION

[0020] The technical solutions in the application are described clearly and completely in combination with specific embodiments of the application. Obviously, the described embodiments are only part of the embodiments of the application, rather than all the embodiments. Based on the embodiments in the application, all other embodiments obtained by those skilled in the art without creative work belong to the protection scope of the application. The methods described in the embodiments of the application are conventional methods, and the materials and reagents used are commercially available, unless otherwise specified.

[0021] Sophora flavescens is purchased from the medicinal material market in Mudanjiang City, and the production place is Hebei.

[0022] Matrine (MT) standard, oxymatrine (OMT) standard, sophoridine (SC) standard and sophoridine (SRI) standard are purchased from China Institute for Drug Control; Na2SO3 is purchased from Tianjin Bodu Chemical Co., Ltd.; thin layer chromatography silica gel G plate is purchased from Qingdao Maik Silicon Drying Agent Co., Ltd.; bismuth subnitrate is purchased from Shantou Xilong Chemical Factory; potassium iodide is purchased from Tianjin Hedong District Hongyan Reagent Factory.

[0023] 1. Preparation of Sophora flavescens percolation solution Take 70g of dry and medium-sized Sophora flavescens granules, and immerse them in 60% ethanol just enough to soak the Sophora flavescens granules. After 20 hours of soaking, load the granules into a percolation cylinder, and then add 60% ethanol to soak the Sophora flavescens granules. After purging gas and adding glass beads to compact the granules, start percolation at a speed of 3mL / min. Collect 1200mL of Sophora flavescens percolate. By using 60% ethanol to extract Sophora flavescens granules, starch impurities can be precipitated and removed, and part of the tannin and protein form can also be precipitated and removed, thereby maximizing the solubility of sophoridine and sophoramine.

[0024] Take 50g of Sophora flavescens powder in 6 portions, and use 250mL of 90%, 80%, 70%, 60%, 50%, and 40% ethanol solution respectively to extract 3 times, 8 hours each time. Combine the extract, filter, and evaporate to dryness to obtain crude base. Repeat twice. The average crude base weight is shown in Table 1.

[0025] Sophora flavescens alkaloids are easily soluble in ethanol solution, and their solubility increases accordingly with the increase of ethanol solution concentration. As shown in Table 1, when the concentration of ethanol solution is increased to 60% or above, the yield of crude base is relatively high and does not change much. That is, when the concentration of ethanol solution is 60% or above, the extraction effect of Sophora flavescens alkaloids is good, and when it is lower than 60%, the extraction effect becomes poor. Therefore, 60% ethanol solution is selected.

[0026] Table 1 Experimental results of Sophora flavescens crude base extraction at different alcohol concentrations Recover ethanol solution from Sophora flavescens percolate in a rotary evaporator at 56°C. After recovering the ethanol solution, continue to recover water from Sophora flavescens percolate in a rotary evaporator at 90°C. Concentrate to 420mL, cool, filter, remove impurities, adjust the pH of Sophora flavescens percolate to 3, and reserve for use. Adjust the pH of Sophora flavescens percolate to acidity by 0.1mol / L hydrochloric acid and 0.1mol / L sodium hydroxide. This can make alkaloids into salt and dissolve in acidic Sophora flavescens percolate, and part of low-polarity substances are insoluble in water and precipitate, thereby further increasing the content of sophoridine and sophoramine in Sophora flavescens percolate.

[0027] 2. Conversion of sophoridine to sophoramine Determination of sophoridine content in Sophora flavescens percolate: Prepare 1mg / mL standard solution of Sophora flavescens alkaloids, oxysophoramine, sophoridine, and sophoridine standard. Take 1L of the above four standard solutions and Sophora flavescens percolate, and use silica gel G plate for sampling. After color development, observe the sampling results, and obtain sophoridine content of about 2.5mg / ml in Sophora flavescens percolate.

[0028] Add 5 mL of Sophora flavescens percolate to each test tube, and conduct experiments with eight test tubes per group at 20℃. The Na₂SO₃ was added at a mass-to-volume ratio of 0.024 g:1 mL to the Sophora flavescens percolate. The optimal reduction time for the conversion of sophoridine to matrine was determined to be 150 minutes. The results are shown in Table 2, and the results of the repeated experiments are shown in Table 3.

[0029] Table 2 Results of the reduction experiment Table 3. Repeated trials of the reduction experiment results Add 5 mL of matrine percolate to each test tube, and conduct experiments with ten test tubes per group at 20℃ for 2.5 h. Determine the conversion rate of sophoridine to matrine after adding different amounts of Na₂SO₃. The specific steps are as follows: Using 10 test tubes as a group, different masses of Na₂SO₃ were added sequentially in increments of 2 mg, with a reaction time of 2.5 h. The content of sophoridine was measured by spotting until sophoridine was completely converted to matrine, thus determining the optimal amount of Na₂SO₃. The results are shown in Table 4. Figure 1 As shown in the figure, the experiment was repeated and the results are shown in Table 5.

[0030] Table 4 Results of the reduction experiment Table 5. Repeated trials of the reduction experiment results This invention converts oxidized matrine into matrine by adding Na2SO3, such as... Figure 1 As shown, adding Na2SO3 can convert sophoridine into matrine, such as... Figure 2 and Figure 3 As shown in Tables 4 and 5, Figure 2 The conversion rate of sophoridine shown is over 98%, proving that this reaction system is stable and reliable.

[0031] Subsequent experiments verified that no significant increase in other matrine alkaloids was observed during catalytic hydrogenation. Due to errors in the extraction and processing of the matrine percolate, other alkaloids may be present in each batch of percolate. Adding sodium sulfite can reduce these alkaloids to their original form, thus the amount of sodium sulfite added will vary accordingly. Therefore, it was confirmed that adding 0.024 g of Na₂SO₃ per milliliter of 2.5 mg / ml SC solution for 2.5 h at room temperature and pressure can achieve relatively complete conversion of SC in the matrine percolate. This reduction method is simple, reliable, and easy to operate, with minimal process requirements, and can be scaled up for industrial operation.

[0032] It will be apparent to those skilled in the art that various modifications and variations can be made to the present application without departing from the spirit or scope of the application. Thus, it is intended that the present application cover modifications and variations of this application provided they come within the scope of the appended claims and their equivalents.

Claims

1. A method for converting matrine to oxymatrine in Sophora flavescens infusion, characterized in that, The method comprises the following steps: Na2SO3 is added to the Sophora flavescens percolation liquid, and a reduction reaction is carried out at 20-25 DEG C to convert sophorin in the Sophora flavescens percolation liquid into matrine; The mass-volume ratio of the Na2SO3 to the Sophora flavescens percolation liquid solution is 0.022-0.024 g:1 mL.

2. The method for improving the conversion of sophoramine to matrine in Sophora flavescens instillation liquid according to claim 1, characterized in that, The mass-volume ratio of the Na2SO3 to the Sophora flavescens percolation liquid solution is 0.024 g:1 mL. The reaction time is 2-3 h.

3. The process for the conversion of sophoramine to matrine in Sophora flavescens infusion solution according to claim 1, characterized in that, The Sophora flavescens percolation liquid is obtained by the following process: The Sophora flavescens soaked with the alcohol reagent is taken out, soaked again in the alcohol reagent, degassed, compacted, and then subjected to percolation treatment to obtain the Sophora flavescens percolation liquid; The outflow speed of the Sophora flavescens percolation liquid is 2-3 mL / min.

4. The method for converting matrine to sophoramine in Sophora flavescens permeation solution according to claim 3, characterized in that, The soaking time is 20-24 h.

5. The method of claim 3, wherein the sophoridine-converted matrine in the Sophora flavescens infusion solution is characterized by, The alcohol reagent is 60-90% ethanol by mass percentage.

6. The process for the conversion of sophoramine to matrine in Sophora flavescens infusion solution according to claim 3, characterized in that, The pH value of the Sophora flavescens percolation liquid is 2-4.

7. The process for the conversion of sophoramine to matrine in Sophora flavescens infusion solution according to claim 3, characterized in that, The Sophora flavescens is Sophora flavescens granules with a particle size of 0.5 cm.

8. The process for the conversion of sophoramine to matrine in Sophora flavescens infusion solution according to claim 3, characterized in that, The Sophora flavescens percolation liquid is further subjected to heating to remove the alcohol reagent before the Na2SO3 is added.

9. The process for the conversion of sophoramine to matrine in Sophora flavescens infusion solution according to claim 3, characterized in that, The compaction is carried out by using glass beads.

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