Processing method of fructus toona and radix aconiti

Abstract

The application provides a prepared process of Radix Aconiti Lateralis Preparata from Fructus Chebulae, which is characterized by the following steps: weighing Fructus Chebulae powder, adding water, soaking for 12 hours, and preparing Fructus Chebulae soup by reflux decocting for 1 hour; putting Radix Aconiti Lateralis into the Fructus Chebulae soup, soaking at room temperature, and turning over daily; drying after turning over for 3 days.

Description

Technical Field

[0001] This application belongs to the pharmaceutical field, specifically providing a method for processing Terminalia chebula into Aconitum carmichaelii. Background Technology

[0002] Mongolian medicine *Aconitum carmichaelii*, the dried tuberous root of *Aconitum carmichaelii* (Ranunculaceae family), is a commonly used medicinal material in Mongolian medicine. It possesses pharmacological effects such as analgesia, anti-inflammation, cardiotonicity, and antitumor activity. However, the raw product contains a large amount of diester-type alkaloids, which are extremely toxic. Used without proper processing, it can cause significant toxicity to the cardiovascular, nervous, and reproductive systems. *Terminalia chebula*, the dried mature fruit of *Terminalia chebula* (Combretaceae family), contains phenolic acids, triterpenes, and tannins. When combined with *Aconitum carmichaelii* and processed, the tannins and alkaloids in *Terminalia chebula* complex with each other, thus preserving the medicinal efficacy while reducing toxicity. This is a classic processing method for reducing the toxicity of *Aconitum carmichaelii* while retaining its efficacy.

[0003] Currently, the traditional processing techniques for processing Terminalia chebula into Aconitum carmichaelii rely heavily on experience and lack unified standards for processing parameters, resulting in unstable toxicity and efficacy of the processed products.

[0004] The content of diester-type aconitine in Aconitum carmichaelii was used as the evaluation index. Single-factor experiments and orthogonal experimental designs were used to investigate the effects of factors such as the ratio of Aconitum carmichaelii to Terminalia chebula, the ratio of Aconitum carmichaelii to Terminalia chebula decoction, and processing time on the processing effect. The optimal processing technology was screened to lay the foundation for the standardization of Aconitum carmichaelii processing, quality standardization, and modern clinical application. Summary of the Invention

[0005] This invention provides a processing method for processing Terminalia chebula into Aconitum carmichaelii, characterized in that Terminalia chebula powder is weighed, water is added, soaked for 12 hours, and decocted under reflux for 1 hour to prepare Terminalia chebula decoction. Aconitum carmichaelii is then soaked in the Terminalia chebula decoction at room temperature, turned over daily for 3 days, and then dried.

[0006] In one embodiment, the processing method provided by the present invention is characterized in that the ratio of aconite and Terminalia chebula powder is 10:3 to 10:7.

[0007] In one embodiment, the processing method provided by the present invention is characterized in that the ratio of aconite powder to Terminalia chebula powder is 10:5.

[0008] In one embodiment, the processing method provided by the present invention is characterized in that the ratio of aconite to water is 1:5 to 1:9.

[0009] In one embodiment, the processing method provided by the present invention is characterized in that the ratio of aconite to water is 1:7.

[0010] In one embodiment, the processing method provided by the present invention is characterized in that the aconite root is soaked in Terminalia chebula decoction for 1 to 5 days.

[0011] In one embodiment, the processing method provided by the present invention is characterized in that the particle size of the Terminalia chebula powder is 20-80 mesh.

[0012] In one embodiment, the processing method provided by the present invention is characterized in that the particle size of the Terminalia chebula powder is 60-80 mesh.

[0013] In one embodiment, the processing method provided by the present invention is characterized in that the daily turning frequency is 5 times, and the turning is carried out for 3 days.

[0014] In one embodiment of the present invention, the drying temperature is 60°C.

[0015] Attached Figure

[0016] Figure 1 Chromatogram of specificity test for raw aconite: Detailed Implementation

[0017] 1. Experimental Materials

[0018] 1.1 Experimental Drugs and Reagents

[0019] Table 1 List of Experimental Drugs and Reagents

[0020]

[0021] 1.2 Experimental Apparatus

[0022] Table 2 List of Experimental Instruments

[0023]

[0024] 2. Experimental Methods and Results

[0025] 2.1 Determination of Aconitum carmichaelii content

[0026] 2.1.1 Chromatographic conditions

[0027] Waters SymmetryR C 18 Chromatographic column (4.6 × 250 mm, 5 µm), mobile phase: 0.02% triethylamine A: methanol B (35:65), flow rate 1 mL / min -1 Detection wavelength: 235nm, column temperature: 35℃.

[0028] 2.1.2 Preparation of reference solution

[0029] Accurately weigh 10 mg of aconitine diester-type alkaloid reference extract (labeled with the contents of neoaconitine, hypoaconitine, and aconitine), add 5 ml of isopropanol:chloroform (1:1) mixed solution and dissolve thoroughly to prepare a mixed reference solution, wherein the concentration of neoaconitine is 0.634 mg / ml. -1 Aconitine was 0.636 mg / ml. -1 Hypoaconitine was 0.6 mg / ml. -1 Shake well and set aside.

[0030] 2.1.3 Preparation of test solution

[0031] Accurately weigh approximately 2 g of raw Aconitum carmichaelii powder that has passed through a No. 3 sieve, place it in a stoppered conical flask, add 3 mL of ammonia test solution, then accurately add 50 mL of a 1:1 mixture of isopropanol and ethyl acetate, weigh, and extract ultrasonically for 30 min. After cooling to room temperature, weigh again, and make up the weight loss with the same mixed solvent. Shake well and filter. Accurately measure 25 mL of the filtrate, evaporate to dryness under reduced pressure below 40 ℃, dissolve the residue in a 1:1 mixture of isopropanol and chloroform, transfer to a 3 mL volumetric flask and dilute to the mark, shake well, and filter to obtain the raw Aconitum carmichaelii test solution.

[0032] 2.1.4 Specificity Test

[0033] The chromatographic conditions described in section "2.1.1" were used for injection analysis, and the results are shown below. Figure 1 The results showed that the test solution exhibited characteristic absorption peaks at the same retention times as the reference solution, the theoretical plate number of the analyte was higher than 3500, and the resolution was greater than 1.5, indicating that the established method has good specificity.

[0034] 2.1.5 Examination of Linear Relationships

[0035] Accurately measure an appropriate amount of the mixed reference solution and dilute it serially according to a certain multiple to prepare six solutions of different concentrations. Take 10 μL of each solution and inject it for analysis under the chromatographic conditions described in section "2.1.1". Plot a standard curve with the reference concentration as the abscissa (X) and the corresponding peak area as the ordinate (Y), and perform linear regression. The results show that the regression equation for neoaconitine is y = 12972267.9063 x + 4576.2576, R0. 2 = 0.9998, linear range: 0.0037~1.8877 mg·g -1 Aconitine y = 12621287.4570 x + 11182.5454, R 2 = 0.9995, linear range: 0.0021~1.8894 mg·g -1; aconitine y = 13237979.0455 x + 5890.3990, R 2 = 0.9997, linear range: 0.0031~1.7848 mg·g -1 .

[0036] 2.1.6 Precision test

[0037] Prepare a raw aconite test solution, accurately pipette 10 μL, and inject repeatedly 6 times according to the chromatographic conditions in “2.1.1”. Measure the three components of aconite, record the chromatographic peak areas, and calculate the RSD values. The values ​​are 0.61% for neoaconitine, 0.86% for aconitine, and 1.19% for hypoaconitine, indicating that the instrument has good precision. The results are shown in Table 3.

[0038]

[0039] 2.1.7 Stability Test

[0040] Prepare a raw aconite test solution, accurately pipette 10 μL, and determine the three components of aconite under the chromatographic conditions in “2.1.1” at 2, 4, 6, 8, 10 and 12 h after preparation. Record the chromatographic peak areas and calculate the RSD values, which are 0.75% for neoaconitine, 1.97% for aconitine and 0.74% for hypoaconitine, indicating that the test solution is basically stable within 12 h. The results are shown in Table 4.

[0041]

[0042] 2.1.8 Repeatability Test

[0043] Six parallel solutions of raw aconite were prepared. 10 μL of each solution was accurately pipetted and the three components of aconite were determined according to the chromatographic conditions in “2.1.1”. The peak areas were recorded and the RSD values ​​were calculated. The results were 1.74% for neoaconitine, 1.90% for aconitine, and 2.00% for hypoaconitine, indicating that the method has good repeatability. The results are shown in Table 5.

[0044]

[0045] 2.1.9 Recovery test

[0046] Six 1 ml portions of the raw aconite test solution were accurately measured. Solid mixed reference standards were added according to the measured content of the sample. The contents of the three components of raw aconite were determined according to the chromatographic conditions in "2.1.1". The recovery rate and relative standard deviation of each component were calculated. The results showed that the average recovery rates of neoaconitine, aconitine and hypoaconitine were 107.48%, 104.34% and 106.56%, respectively, and the RSDs were 1.27%, 0.61% and 1.30%, respectively. The results are shown in Table 6.

[0047]

[0048] 2.1.10 Determination of Sample Content

[0049] Six batches of test solutions were prepared according to the method in section “2.1.1”. Each batch of sample solution was injected 6 times. The peak areas of neoaconitine, aconitine and hypoaconitine were determined and the contents of the sample solution were calculated. The results are shown in Table 7.

[0050]

[0051] 2.2 Single-factor experiment on the processing technology of Terminalia chebula and Aconitum carmichaelii

[0052] 2.2.1 Investigation into the ratio of Aconitum carmichaelii and Terminalia chebula in decoction

[0053] Weigh out Aconitum carmichaelii rhizome and Terminalia chebula coarse powder at a mass ratio of 10:3, with Terminalia chebula particle size of 20-60 mesh. Add water to Terminalia chebula at ratios of Aconitum carmichaelii:water = 1:5, 1:7, and 1:9 respectively, soak for 12 hours, and reflux and decoct for 1 hour to obtain Terminalia chebula decoction. Accurately weigh 10g of Aconitum carmichaelii, soak in Terminalia chebula decoction at room temperature for 3 days, turning 5 times daily for 3 days, until a slight numbing sensation is felt on the tongue. Remove and dry at 60℃; pulverize before use. Prepare the test solution according to the method in section "2.1.3", and determine the content of index components under the chromatographic conditions in section "2.1.1". The results are shown in Table 8. The results show that the total aconitine content in samples with different ratios is 1:5 > 1:9 > 1:7, indicating that the ratio of Aconitum carmichaelii to Terminalia chebula has a significant impact on the total content of the three aconitines in the processed product.

[0054]

[0055] 2.2.2 Investigation into the ratio of Aconitum carmichaelii to Terminalia chebula

[0056] Weigh out Aconitum carmichaelii rhizome and Terminalia chebula coarse powder (Terminalia chebula particle size 20-60 mesh) at mass ratios of 10:3, 10:5, and 10:7 respectively. Add water to Terminalia chebula at a mass ratio of Aconitum carmichaelii:water = 1:7, soak for 12 hours, and reflux and decoct for 1 hour to obtain Terminalia chebula decoction. Place the processed Aconitum carmichaelii into the above-prepared Terminalia chebula decoction and soak at room temperature for 3 days, turning 5 times daily for 3 days, until a slight numbing sensation is felt on the tongue. Remove and dry at 60℃; pulverize before use. Prepare the test solution according to the method in section "2.1.3", and determine the content of index components under the chromatographic conditions in section "2.1.1". The results are shown in Table 9. The results show that the total aconitine content in samples with different ratios is 10:3 > 10:7 > 10:5, indicating that the ratio of Aconitum carmichaelii to Terminalia chebula has a significant impact on the total content of the three aconitines in the processed product.

[0057]

[0058] 2.2.3 Examination of soaking time

[0059] Weigh out Aconitum carmichaelii rhizome and Terminalia chebula coarse powder (Terminalia chebula particle size 20-60 mesh) at a mass ratio of 10:5. Add water to the Terminalia chebula at a ratio of Aconitum carmichaelii:water = 1:7, soak for 12 hours, and then reflux and decoct for 1 hour to obtain Terminalia chebula decoction. Place the Aconitum carmichaelii in the obtained Terminalia chebula decoction and soak at room temperature for 3, 4, and 5 days, turning it 5 times daily for 3 days. Remove when a slight numbing sensation is felt on the tongue, and dry at 60℃. Grind before use. Prepare the test solution according to the method in section "2.1.3", and determine the content of index components under the chromatographic conditions in section "2.1.1". The results are shown in Table 10. The results show that the total alkaloid content in samples processed for different times is in the order of 4 days > 2 days > 3 days, indicating that soaking time has a significant effect on the total content of the three aconitines in the processed product.

[0060]

[0061] 2.2.4 Investigation of Terminalia chebula particle size

[0062] According to the mass ratio of Aconitum carmichaelii to Terminalia chebula (Terminalia chebula) = 10:5, Aconitum carmichaelii rhizome and Terminalia chebula powder of three different particle sizes (20-40 mesh, 40-60 mesh, and 60-80 mesh) were weighed out. Water was then added to the Terminalia chebula powder at a ratio of Aconitum carmichaelii to water of 1:7, and the mixture was soaked for 12 hours, then refluxed and decocted for 1 hour to obtain Terminalia chebula decoction. Aconitum carmichaelii was placed in the above Terminalia chebula decoction and soaked at room temperature for 3 days, turning it 5 times a day for 3 days, until a slight numbing sensation was felt on the tongue. It was then removed, dried at 60℃, and pulverized before use. The content of index components was tested under the conditions in section "2.1.1", and the results are shown in Table 13. The results show that the total alkaloid content in processed Aconitum carmichaelii of different particle sizes is in the order of 20-40 mesh > 40-60 mesh > 60-80 mesh, indicating that the particle size of Terminalia chebula has a significant impact on the total content of the three aconitines in the processed product.

[0063] The test solution was prepared using the method described in section "2.1.1", and the content of the index components was detected under these conditions. The results are shown in Table 11. The results indicate that 20-40 mesh > 40-60 mesh > 60-80 mesh, and the particle size of Terminalia chebula has a significant impact on the total content of the three aconitines in the processed product.

[0064]

[0065] 2.3 Orthogonal Experiment on Processing Technology of Terminalia chebula and Aconitum carmichaelii

[0066] Accurately weigh raw aconite and chebula, soak the aconite in chebula decoction, and use the content of neoaconitine, hypoaconitine, and aconitine, as well as the total content, as the main evaluation indicators to screen the optimal processing technology. Four factors were selected: aconite and chebula decoction (A), aconite and chebula (B), soaking time (C), and chebula particle size (D). Each factor was set with three levels, using L9(3). 4 The orthogonal array design experiment is shown in Table 12, and the orthogonal experimental design and results are shown in Table 13.

[0067]

[0068]

[0069] Table 13 shows that the effects of the four factors on the total aconitine content are B > A > C > D, with the optimal condition being A2B2C2D3; the effects on neoaconitine are C > A > B > D, with the optimal condition being A2B3C2D3; the effects on aconitine are D > B > C > A, with the optimal condition being A2B2C1D3; and the effects on hypoaconitine are B > A > C > D, with the optimal condition being A3B2C2D2.

[0070] 3. Summary

[0071] Preparation of Terminalia chebula decoction: Weigh out Aconitum carmichaelii root and Terminalia chebula coarse powder (60-80 mesh) at a mass ratio of 10:3 and mix them evenly; then add water to Terminalia chebula at a mass ratio of Aconitum carmichaelii:water = 1:7, soak for 12 hours, reflux and decoct for 1 hour to make Terminalia chebula decoction.

[0072] Soaking and processing: Place the aconite in the above-mentioned Terminalia chebula decoction and soak at room temperature for 3 days, turning it 5 times a day for 3 days, until it is only slightly numbing on the tongue when tasted.

[0073] Drying the finished product: The soaked Aconitum carmichaelii is dried at a low temperature of 60℃ to obtain processed Aconitum carmichaelii.

[0074] Optimized processing of Terminalia chebula into Aconitum carmichaelii can effectively reduce the content of aconitine, thereby reducing the toxicity of Aconitum carmichaelii.

Claims

1. A processing method for Terminalia chebula and Aconitum carmichaelii, characterized in that, Weigh out Terminalia chebula powder, add water, soak for 12 hours, reflux and decoct for 1 hour to prepare Terminalia chebula decoction, put Aconitum carmichaelii into Terminalia chebula decoction and soak at room temperature, turning it over daily for 3 days, then dry.

2. The processing method according to claim 1, characterized in that, The ratio of aconite powder to Terminalia chebula powder is 10:3 to 10:

7.

3. The processing method according to claim 2, characterized in that, The ratio of aconite powder to Terminalia chebula powder is 10:

5.

4. The processing method according to claim 1 or 2, characterized in that, The ratio of aconite to water is 1:5 to 1:

9.

5. The processing method according to claim 4, characterized in that, The ratio of aconite to water is 1:

7.

6. The processing method according to claims 1-5, characterized in that, The aconite root is soaked in the Terminalia chebula decoction for 1 to 5 days.

7. The processing method according to claim 6, characterized in that, The particle size of the Terminalia chebula powder is 20-80 mesh.

8. The processing method according to claim 7, characterized in that, The particle size of the Terminalia chebula powder is 60-80 mesh.

9. The processing method according to claims 1-8, characterized in that, The recommended number of times to turn over each day is 5.

10. The processing method according to claims 1-9, characterized in that, The drying temperature is 60°C.

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