A method for removing heavy metals in the process of traditional Chinese medicine extraction

Abstract

The application discloses a treatment method for removing heavy metals in a traditional Chinese medicine extraction process and relates to the technical field of traditional Chinese medicine preparation safety. The method for simultaneously removing Cu, Cd, As, Hg and Pb five kinds of heavy metals in the traditional Chinese medicine extraction process provided by the application can reduce the content of heavy metals below the safety limit, and can achieve the purpose of eliminating the safety hidden danger of heavy metals in traditional Chinese medicine preparations. After the heavy metals are removed by sodium alginate, the loss of effective components of the traditional Chinese medicine is small, the similarity of the traditional Chinese medicine fingerprint spectrum before and after the heavy metals are removed is above 0.9, and the medicinal value is not affected. The sodium alginate is low in price and green in environment protection, and can be used for removing heavy metals in the traditional Chinese medicine extraction process, so that convenient technical means and reliable scientific basis can be provided for guaranteeing the safety of clinical application of traditional Chinese medicine preparations.

Description

Technical Field

[0001] A method for removing five heavy metals during the extraction process of Chinese medicinal materials and Chinese medicine preparations (Chinese medicine formula granules, Chinese patent medicines) is involved in the field of safety research on the processing of Chinese medicinal materials. Background Technology

[0002] my country boasts abundant traditional Chinese medicinal resources, and traditional Chinese medicine has a long history of treating diseases and maintaining health. Due to its unique therapeutic effects, the international demand for traditional Chinese medicine has been increasing since China's accession to the WTO. However, environmental and soil pollution, as well as the accumulation of pesticides and fertilizers, have led to increasingly serious heavy metal contamination in medicinal herbs. Heavy metals enter the human body through ingested medicinal herbs, disrupting metabolic processes and potentially inhibiting normal physiological functions. A series of poisoning incidents caused by excessive heavy metals in medicinal herbs, along with export returns, have damaged the international reputation of traditional Chinese medicine and hindered its rapid development in international trade. Therefore, exploring a more effective and precise method for removing heavy metals from medicinal herbs has become an urgent issue to be addressed.

[0003] Heavy metals in traditional Chinese medicine (TCM) preparations such as herbal granules mainly originate from the extracted medicinal herbs. Excessive heavy metal content in these herbs can affect the quality and safety of the TCM preparations. Therefore, it is necessary to incorporate a fast, appropriate, green, and safe method for removing heavy metals into the formulation process of granules to reduce the heavy metal content in the herbal extracts and avoid safety hazards caused by contaminated herbs.

[0004] As a common natural macromolecule, sodium alginate is increasingly used in emerging fields such as biotechnology, biopharmaceuticals, and environmental remediation due to its good biocompatibility, lack of toxicity, and low cost. The molecular chain of sodium alginate contains abundant hydroxyl and carboxyl groups, which can undergo complexation reactions with divalent metal cations, and it is often used as an adsorbent in research on heavy metal removal. However, there are almost no reports in domestic or international patents regarding the application of sodium alginate in the removal of heavy metals from traditional Chinese medicine. Summary of the Invention

[0005] The purpose of this invention is to provide a method for removing harmful heavy metals during the extraction process of traditional Chinese medicine preparations (Chinese medicine formula granules, traditional Chinese medicine preparations).

[0006] This invention is achieved through the following technical solution:

[0007] The application of heavy metal removal in the extraction process of traditional Chinese medicine preparations (TCM formula granules, prepared Chinese medicines) includes the following steps:

[0008] Step 1: Add a certain proportion of sodium alginate to the Chinese medicinal herbs;

[0009] Step 2: Soak the Chinese medicinal herbs mixed with sodium alginate in water, then decoct them, filter them, add water to the dregs and decoct them again, and combine the two filtrates.

[0010] Step 3: After cooling the filtrate, centrifuge, concentrate, and precipitate with alcohol to obtain a Chinese herbal extract with low heavy metal content.

[0011] The preparation process described in step two may also include the following steps:

[0012] Weigh out an appropriate amount of Chinese medicinal herbs, soak them in 10 times the amount of water for 2 hours, decoct for 180 minutes and filter. Add 10 times the amount of water to the dregs and decoct again for 120 minutes. Combine the two filtrates.

[0013] The preparation process described in step three may also include the following steps:

[0014] After rapidly cooling the filtrate, centrifuge to remove impurities (7000 r / min, 10 min), collect the supernatant, concentrate it, add ethanol to the filtrate to make the ethanol concentration 75%, stir well, let stand for 24 h, collect the supernatant and recover the ethanol, concentrate and make up to volume.

[0015] The method for removing heavy metals described in this invention can be used to simultaneously remove five heavy metals—Pb, Cd, As, Hg, and Cu—from traditional Chinese medicine preparations, ensuring that the heavy metal residue values ​​meet the standard requirements and improving the safety of medication.

[0016] The heavy metal adsorbent described in this invention is sodium alginate, a pharmaceutical excipient grade. Its molecular chain contains abundant carboxyl and hydroxyl groups, which can undergo complexation reactions with divalent metal cations.

[0017] The advantage of this invention lies in the fact that materials used for removing heavy metals in traditional Chinese medicine preparations need to be selected that neither introduce toxic impurities nor react with the main components to affect the efficacy of the original process. Sodium alginate, selected in this invention, has been awarded the "Generally Recognized as Safe" designation by the U.S. Food and Drug Administration (FDA). It is non-toxic, relatively stable, and inexpensive, possessing strong gelling and complexing abilities, as well as biocompatibility and biodegradability, thus having a basis for green applications. Combining sodium alginate with the traditional Chinese medicine preparation process allows for the removal of heavy metals from traditional Chinese medicine preparations without affecting their efficacy, introducing impurities, or adding excessively complicated procedures. Attached Figure Description

[0018] Figure 1 This is a comparison of the HPLC fingerprint of Paeonia lactiflora 1 before and after adsorption of heavy metals;

[0019] Figure 2 This is a comparison of the HPLC fingerprint spectra of Paeonia lactiflora before and after heavy metal adsorption;

[0020] Figure 3 This is a comparison of the HPLC fingerprint of Astragalus membranaceus before and after heavy metal adsorption;

[0021] Figure 4 This is a comparison of the HPLC fingerprints of Astragalus membranaceus before and after heavy metal adsorption. Detailed Implementation

[0022] The technical solution of the present invention will be further described below with reference to specific implementation methods and accompanying drawings, but this does not limit the scope of the present invention.

[0023] Five heavy metal solutions (Pb, Cd, As, Hg, and Cu) were added to the weighed Chinese medicinal materials to make the heavy metal content of the medicinal materials exceed the limit by 1 time, that is, the mass ratio of each metal ion to the medicinal materials was 5 μg / g lead, 1 μg / g cadmium, 2 μg / g arsenic, 0.2 μg / g mercury, and 20 μg / g copper.

[0024] Example 1

[0025] (1) Weigh an appropriate amount of white peony root sample, soak it in ultrapure water, and precisely add appropriate amounts of As, Cd, Cu, Hg, and Pb element standard solutions in proportion to make the heavy metal content of the Chinese medicinal material exceed the standard by 1 time. Add sodium alginate at a ratio of 100:1 of medicinal material to sodium alginate and stir. Soak in ultrapure water at a mass ratio of 1:10 for 2 hours.

[0026] (2) Heat (1) to boiling for 180 min, cool for 10-15 min, filter out the dregs, and retain the filtrate A;

[0027] (3) Put the dregs from (2) into a cooking vessel, add 10 times the amount of pure water by mass, boil again for 120 minutes, cool to room temperature, filter out the dregs, and keep the filtrate B.

[0028] (4) Combine filtrate A and filtrate B, centrifuge to remove impurities, separate the upper liquid, concentrate it, and make up to a fixed volume;

[0029] (5) Add ethanol to the drug solution obtained in (4), stir well, let stand for 24 h, take the supernatant and recover the ethanol, concentrate and make up to volume as the sample solution, and evaluate the adsorption effect of sodium alginate by comparing the changes in the concentration of each ion before and after adsorption.

[0030] Example 2

[0031] (1) Weigh an appropriate amount of white peony root sample, soak it in ultrapure water, and precisely add appropriate amounts of As, Cd, Cu, Hg, and Pb element standard solutions in proportion to make the heavy metal content of the Chinese medicinal material exceed the standard by 1 time. Add sodium alginate at a ratio of 100:1 of medicinal material to sodium alginate and stir. Soak in ultrapure water at a mass ratio of 1:10 for 2 hours.

[0032] (2) Heat (1) to boiling for 180 min, cool for 10-15 min, filter out the dregs, and retain the filtrate A;

[0033] (3) Put the dregs from (2) into a cooking vessel, add 10 times the amount of pure water by mass, boil again for 120 minutes, cool to room temperature, filter out the dregs, and keep the filtrate B.

[0034] (4) Combine filtrate A and filtrate B, centrifuge to remove impurities, separate the upper liquid, concentrate it, and make up to a fixed volume;

[0035] (5) Add ethanol to the drug solution obtained in (4), stir well, let stand for 24 h, take the supernatant and recover the ethanol, concentrate and make up to volume as the sample solution, and evaluate the adsorption effect of sodium alginate by comparing the changes in the concentration of each ion before and after adsorption.

[0036] Example 3

[0037] (1) Weigh an appropriate amount of Astragalus membranaceus sample, soak it in ultrapure water, and precisely add appropriate amounts of As, Cd, Cu, Hg, and Pb element standard solutions in proportion to make the heavy metal content of the Chinese medicinal material exceed the standard by 1 time. Add sodium alginate at a ratio of 100:1 of medicinal material to sodium alginate and stir. Soak in ultrapure water at a mass ratio of 1:10 for 2 hours.

[0038] (2) Heat (1) to boiling for 180 min, cool for 10-15 min, filter out the dregs, and retain the filtrate A;

[0039] (3) Put the dregs from (2) into a cooking vessel, add 10 times the amount of pure water by mass, boil again for 120 minutes, cool to room temperature, filter out the dregs, and keep the filtrate B.

[0040] (4) Combine filtrate A and filtrate B, centrifuge to remove impurities, separate the upper liquid, concentrate it, and make up to a fixed volume;

[0041] (5) Add ethanol to the drug solution obtained in (4), stir well, let stand for 24 h, take the supernatant and recover the ethanol, concentrate and make up to volume as the sample solution, and evaluate the adsorption effect of sodium alginate by comparing the changes in the concentration of each ion before and after adsorption.

[0042] Example 4

[0043] (1) Weigh an appropriate amount of Astragalus membranaceus sample, soak it in ultrapure water, and precisely add appropriate amounts of As, Cd, Cu, Hg and Pb element standard solutions in proportion to make the heavy metal content of the Chinese medicinal material exceed the standard by 1 time. Add sodium alginate at a ratio of 100:1 of medicinal material to sodium alginate and stir. Soak in ultrapure water at a mass ratio of 1:10 for 2 hours.

[0044] (2) Heat (1) to boiling for 180 min, cool for 10-15 min, filter out the dregs, and retain the filtrate A;

[0045] (3) Put the dregs from (2) into a cooking vessel, add 10 times the amount of pure water by mass, boil again for 120 minutes, cool to room temperature, filter out the dregs, and keep the filtrate B.

[0046] (4) Combine filtrate A and filtrate B, centrifuge to remove impurities, separate the upper liquid, concentrate it, and make up to a fixed volume;

[0047] (5) Add ethanol to the drug solution obtained in (4), stir well, let stand for 24 h, take the supernatant and recover the ethanol, concentrate and make up to volume as the sample solution, and evaluate the adsorption effect of sodium alginate by comparing the changes in the concentration of each ion before and after adsorption.

[0048] Comparative Example 1

[0049] The difference between Comparative Example 1 and Example 1 is that in step (1) of Comparative Example 1, sodium alginate is added and mixed according to the ratio of medicinal material to sodium alginate of 50:1.

[0050] Comparative Example 2

[0051] The difference between Comparative Example 2 and Example 2 is that in step (1) of Comparative Example 1, sodium alginate was added and mixed at a ratio of 50:1 between the amount of medicinal material and the amount of sodium alginate.

[0052] Comparative Example 3

[0053] The difference between Comparative Example 3 and Example 3 is that in step (1) of Comparative Example 1, sodium alginate was added and mixed at a ratio of 50:1 between the amount of medicinal material and the amount of sodium alginate.

[0054] Comparative Example 4

[0055] The difference between Comparative Example 4 and Example 4 is that in step (1) of Comparative Example 1, sodium alginate was added and mixed at a ratio of 50:1 between the amount of medicinal material and the amount of sodium alginate. Table 1 shows the removal rates of the five heavy metals in each group.

[0056] Cu As Cd Hg Pb Example 1 75.66% 62.32% 100.19% 71.25% 99.43% Example 2 72.14% 51.11% 100.07% 95.00% 95.89% Example 3 65.28% 33.37% 99.79% 36.88% 97.89% Example 4 63.59% 46.03% 99.91% 75.00% 99.40% Comparative Example 1 74.50% 41.02% 100.06% 87.50% 98.88% Comparative Example 2 75.70% 54.29% 100.13% 99.38% 99.86% Comparative Example 3 68.09% 38.60% 99.47% 61.25% 97.41% Comparative Example 4 67.08% 50.93% 100.18% 85.00% 97.35%

[0057] To investigate the effect of sodium alginate removal of heavy metals on the components of traditional Chinese medicine (TCM), HPLC was used to determine the content of main components in the TCM extract after heavy metal removal. Paeoniflorin was selected as the designated component of white peony root, and astragaloside A was selected as the designated component of astragalus root. The changes in the content of these designated components were used to evaluate the differences in the effective components of white peony root and astragalus root before and after heavy metal removal. The results are shown in the table below. The changes in content before and after adsorption were relatively small. Table 2: Changes in Paeoniflorin content after heavy metal removal.

[0058] content% White peony root 1 before processing 1.71 Example 1 1.61 Comparative Example 1 1.65 White peony root 2 before treatment 2.12 Example 2 2.11 Comparative Example 21 2.00

[0059] Table 3. Changes in astragaloside A content after heavy metal removal.

[0060] Astragaloside A content % Astragalus membranaceus 1 before processing 0.0505 Example 3 0.0467 Comparative Example 3 0.0482 Astragalus 2 before processing 0.0224 Example 4 0.0209 Comparative Example 4 0.0192

[0061] Given that the determination of a single active ingredient cannot fully reflect the overall quality of traditional Chinese medicine, a high-performance liquid chromatography (HPLC) fingerprint analysis method for Astragalus membranaceus (Huang Qi) and Paeonia lactiflora (Bai Shao) extracts was established. The chromatograms were analyzed using the Similarity Evaluation System of Chromatographic Fingerprint of TCM (Version 2012 A) provided by the National Pharmacopoeia Commission to examine the consistency of the quality of Astragalus membranaceus and Paeonia lactiflora extracts before and after heavy metal removal with sodium alginate. Comparison Figure 1 and Figure 2 The similarity evaluation results of samples 1 and 2 of white peony root were both greater than 0.99, indicating excellent consistency between the samples before and after heavy metal removal using sodium alginate. (Comparison) Figure 3 and Figure 4 The fingerprint spectra of samples Astragalus 1 and Astragalus 2 showed a high similarity of 0.94 compared with the control fingerprint spectra, and the samples before and after heavy metal removal by sodium alginate showed good consistency.

[0062] Figure 1 and Figure 2 S1–S3 and S4–S6 represent two sets of chromatograms before and after sodium alginate removal of heavy metals from peony root, respectively. Figure 3 and Figure 4 S1–S3 and S4–S6 represent two sets of chromatograms before and after sodium alginate removal of heavy metals from Astragalus membranaceus, respectively. The fingerprint chromatograms of the samples showed high similarity, indicating good consistency between the samples before and after sodium alginate removal of heavy metals.

[0063] By comprehensively analyzing the changes in the content of indicator components and HPLC fingerprint of traditional Chinese medicine extracts before and after the removal of heavy metals by sodium alginate, the results showed that the chemical composition of Astragalus membranaceus and Paeonia lactiflora did not change significantly after the removal of heavy metals Cu, Cd, As, Hg and Pb by sodium alginate, and the heavy metal content was significantly reduced. This achieved the experimental design goal of accurately and effectively removing heavy metals under the premise of protecting the effective components of traditional Chinese medicine, and this method has good application advantages.

Claims

1. A method for removing heavy metals from traditional Chinese medicine during extraction, characterized in that, The specific steps are as follows: 1) Put the Chinese medicinal materials into a cooking vessel, add sodium alginate according to the ratio of medicinal material quantity to sodium alginate quantity of 100-50:1, stir and mix well, then add pure water at a mass ratio of 1:10, and stand for 2 hours of soaking; 2) Heat and boil for 180 min, cool for 10-15 min, filter out the medicinal residue, and reserve the filtrate A; 3) Put the medicinal residue in 2) into the cooking vessel, add 10 times the mass of pure water, boil again for 120 min, cool to room temperature, filter out the medicinal residue, and reserve the filtrate B; 4) Combine the filtrate A and the filtrate B, remove impurities by centrifugation, separate the upper medicinal liquid, concentrate, and constant volume; 5) Add ethanol to the medicinal liquid obtained in 4) to make the ethanol concentration of the medicinal liquid 75%, stir well, stand for 24 h, take the supernatant, recover the ethanol, concentrate, and constant volume; The heavy metal elements include lead ions, chromium ions, arsenic ions, mercury ions, and copper ions.

2. The method for removing heavy metals in the process of traditional Chinese medicine extraction according to claim 1, characterized in that, The heavy metal adsorbent is medicinal material grade sodium alginate.

3. The method for removing heavy metals from traditional Chinese medicine according to claim 1, characterized in that, The centrifuge speed in 4) is 7000 r / min, and the centrifugation time is 10 min.

4. The method for removing heavy metals in the process of traditional Chinese medicine extraction according to claim 1, characterized in that, The heavy metal adsorbent is directly added into the Chinese medicinal materials to remove heavy metal ions in the process of extracting Chinese medicinal materials.

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