Method for preparing palmatine

Abstract

The invention provides a method for preparing palmatine. According to the method, L-tetrahydropalmatine is used as at least part of raw materials. The method for preparing the palmatine from the L-tetrahydropalmatine has the advantages of simplicity in operation, environmental protection, low cost and the like, and is high in application value.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medicine. Specifically, the present application relates to a method for preparing tetrandrine. BACKGROUND

[0002] Tetrandrine, also known as Sanguilignan, Palmatine and Palmatin, is a natural isoquinoline alkaloid active compound extracted from the dried stems of the plant Tetraena mongolica Maxim. of the family Menispermaceae. Studies have shown that tetrandrine has the effects of antioxidation, anti-inflammation, antibiosis and immunity enhancement, especially the antibiosis effect, which has been confirmed by a large number of pharmacological studies.

[0003]

[0004] The clinical medicinal value of tetrandrine has been widely recognized, and it has shown outstanding advantages in treatment effect and safety. Therefore, the demand for tetrandrine has been growing in recent years. However, the growth cycle of the tetrandrine crop is long, and it usually needs to be planted for more than 7 years before it can be used for medicinal purposes. In addition, when preparing tetrandrine from tetraena mongolica maxim plants, the plants need to be uprooted, which is devastating to natural resources, leading to a shortage of raw material resources and an increase in product prices.

[0005] Therefore, the current preparation method of tetrandrine needs to be studied. SUMMARY

[0006] In view of this, at least one object of the present application is to make up for the deficiencies in the preparation of tetrandrine, to cope with the shortage of natural tetraena mongolica maxim resources, to reduce the production cost of the product, and to avoid the problems that the existing synthetic preparation technology often involves a large number of experimental reaction processes, a long reaction route, a complicated procedure, inconvenient operation, some methods require high laboratory requirements and are not suitable for industrial production, or involve the use of a large amount of organic solvent, which produces toxic and harmful waste and does not meet the green and environmental protection concept. Therefore, the present application proposes to use levorotatory tetrahydropalmatine to prepare tetrandrine, which has the advantages of simple operation, environmental protection, low cost and high application value.

[0007] In a first aspect of the present application, the present application proposes the use of levorotatory tetrahydropalmatine in the preparation of tetrandrine. The inventors of the present application have creatively found that levorotatory tetrahydropalmatine can be used as a raw material to prepare tetrandrine.

[0008]

[0009] In a second aspect of the present application, the present application proposes a method for preparing tetrandrine, which uses levorotatory tetrahydropalmatine as at least part of the raw material. The inventors of the present application have creatively found that levorotatory tetrahydropalmatine can be used as a raw material to prepare tetrandrine.

[0010] According to the embodiments of the present application, the method for preparing tetrandrine can further have the following additional technical features:

[0011] According to the embodiments of the present application, the method comprises: irradiating the levorotatory tetrahydropalmatine with ultraviolet light to generate tetrandrine. Compared with other treatment methods, irradiating the levorotatory tetrahydropalmatine with ultraviolet light can promote the conversion of the levorotatory tetrahydropalmatine into tetrandrine.

[0012] According to the embodiments of the present application, the method comprises: step (1): irradiating a levorotatory tetrahydropalmatine solution with ultraviolet light to obtain a reaction liquid, and collecting supernatant in the reaction liquid, the supernatant containing tetrandrine; and step (2): mixing the precipitate in the reaction liquid with water, and then repeating the operation of step (1) at least once to combine the supernatant in the reaction liquid. After the levorotatory tetrahydropalmatine solution is irradiated with ultraviolet light, the reaction liquid is divided into supernatant containing the generated tetrandrine and precipitate, the supernatant is collected, and the lower layer precipitate is mixed with water again and reacted repeatedly, so as to more fully convert the levorotatory tetrahydropalmatine into tetrandrine and improve the yield of tetrandrine.

[0013] According to the embodiments of the present application, the solvent in the levorotatory tetrahydropalmatine solution comprises water. In some embodiments, the levorotatory tetrahydropalmatine solution only contains water. In this way, no organic solvent is used, and the environment is green.

[0014] According to the embodiments of the present application, the concentration of the levorotatory tetrahydropalmatine in the levorotatory tetrahydropalmatine solution is 0.001 mg / mL to 0.1 mg / mL. In this way, the conversion of the levorotatory tetrahydropalmatine into tetrandrine can be further promoted, and the yield of tetrandrine is improved.

[0015] According to the embodiments of the present application, in step (1), the ultraviolet light irradiation is performed by using an ultraviolet lamp, the irradiation power of the ultraviolet lamp is 700 to 1000 W, and the time is 0.5 h to 2 h. In this way, the conversion of the levorotatory tetrahydropalmatine into tetrandrine can be further promoted, the yield of tetrandrine is improved, and the treatment time is shortened.

[0016] According to the embodiments of the present application, step (2) further comprises: performing rotary evaporation and drying treatment on the combined supernatant.

[0017] Additional aspects and advantages of the present application will be made apparent from the following description. BRIEF DESCRIPTION OF DRAWINGS

[0018] The above and / or additional aspects and advantages of the present application will become apparent and be readily understood from the following description, taken in conjunction with the accompanying drawings, in which:

[0019] Figure 1A solution of the physical map is shown according to one embodiment of the present application, from left to right, respectively, the aqueous solution of the reference of dictamnin, the aqueous solution of example 1 and the aqueous solution of example 2;

[0020] Figure 2 A HPLC analysis chromatogram is shown according to one embodiment of the present application;

[0021] Figure 3 A high resolution mass spectrum is shown according to one embodiment of the present application, (1) dictamnin reference, (2) sample. DETAILED DESCRIPTION

[0022] The scheme of the present application will be explained below in conjunction with examples. Those skilled in the art will understand that the following examples are only for illustration of the present application and should not be regarded as limiting the scope of the present application. If the specific technology or condition is not specified in the examples, it is carried out according to the technology or condition described in the literature in the art or according to the product instruction. If the reagent or instrument is not specified by the manufacturer, it is a conventional product that can be obtained by purchase in the market.

[0023] Example 1

[0024] 1. Take 20 mg of levorotatory tetrahydropalmatine and put it in a beaker, add 100 mL of distilled water, stir uniformly, and then place it under ultraviolet radiation treatment for 1 h, with a power of 864 W. Collect the upper yellow-green solution (as shown in Figure 1 ). The remaining unreacted lower layer precipitate is continuously added with a small amount of distilled water to make the water cover the lower layer precipitate, and after repeating 2 times, the upper layer filtrate is combined. After removing most of the water from the filtrate by rotary evaporation, it is placed in an oven for drying to obtain 11 mg of dictamnin powder, with a yield of 55%.

[0025] 2. After adding 2 ml of ultrapure water to the following experimental groups respectively, HPLC analysis is carried out.

[0026] Experimental group 1: dictamnin reference.

[0027] Experimental group 2: sample 1 and sample 2 (prepared dictamnin powder, parallel sample).

[0028] Experimental group 3: dictamnin + sample (dictamnin reference and prepared dictamnin powder mixed in a ratio of 1:1)

[0029] The HPLC analysis conditions are as follows:

[0030] Octadecylsilane-bonded silica gel was used as the packing material; trifluoroacetic acid-water (0.1:100) was used as mobile phase A; trifluoroacetic acid-acetonitrile (0.1:100) was used as mobile phase B. The detection wavelength was 280 nm, the column temperature was 35 °C, and the flow rate was 1.0 mL / min. Linear gradient elution was performed (0.01 min–35.00 min, A: 90%–50%; 35.00 min–40.00 min, A: 50%–90%; 40.00 min–50.00 min, A: 90%–90%). Instrument information and data were collected and processed by SHIMADZU LabSolutions.

[0031] The results are as follows Figure 2 As shown, both the standard and prepared berberine powder showed obvious characteristic peaks at 29.7 minutes, while no such peaks were observed in the levo-tetrahydropalmatine (sample).

[0032] 3. After adding 2 ml of ultrapure water to the samples from experimental group 2 and experimental group 3 (containing berberine+), high-resolution mass spectrometry analysis was performed. The results are as follows: Figure 3 As shown, the parent ion peak of both the sample and the standard is 352 m / z. The characteristic fragment ion peaks of the berberine standard are 336 m / z and 308 m / z, which were also detected in the mass spectrum of the sample. Therefore, based on the mass spectrometry information, it was determined that the product obtained after processing levo-tetrahydropalmatine is berberine.

[0033] Example 2

[0034] Weigh 50 mg of levamisole into a beaker, add 100 mL of distilled water, stir well, and then place under ultraviolet light for 1 hour at a power of 864 W. Collect the upper yellow-green solution (e.g., Figure 1 The remaining unreacted powder was further mixed with a small amount of distilled water, and this process was repeated several times. The upper filtrates were then combined. After removing most of the water from the filtrate using rotary evaporation, it was dried in an oven to obtain 28 mg of berberine powder, with a yield of 56%.

[0035] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention.

Claims

1. Use of levorphanol in the preparation of lufuradom.

2. A method for preparing palmatine, characterized by, The method uses levorphanol as at least part of the raw material.

3. The method of claim 2, wherein, The method comprises: The method comprises:

4. The method of claim 2, wherein, Step (1): UV irradiation of a levorphanol solution to obtain a reaction solution, and collecting supernatant in the reaction solution, wherein the supernatant contains lufuradom; Step (2): mixing the precipitate in the reaction solution with water, and then repeating the operation of step (1) at least once, and combining the supernatant in the reaction solution. The solvent in the levorphanol solution comprises water; 5. The method of claim 4, wherein, The concentration of levorphanol in the levorphanol solution is 0.001 mg / mL to 0.1 mg / mL. In step (1), the UV irradiation is performed using a UV lamp, and the irradiation power of the UV lamp is 700 to 1000 W, and the time is 0.5 h to 2 h.

6. The method of claim 4, wherein, Step (2) further comprises: rotary evaporation and drying treatment of the combined supernatant.

7. The method of claim 4, wherein, ​

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