Method for removing mercury from bilirubin

Abstract

The invention relates to the technical field of cholesterol preparation, and discloses a bilirubin mercury removal method which comprises the following steps: 1) preparing a bilirubin calcium salt or a bilirubin crude product into a sodium bilirubin aqueous solution; 2) adding activated carbon into the sodium bilirubin aqueous solution for primary adsorption, and performing solid-liquid separation to obtain a primary purified solution and primary adsorption activated carbon; 3) diluting the primary purified solution with water, adding activated carbon for secondary adsorption, and performing solid-liquid separation to obtain a secondary purified solution; 4, hydrochloric acid is added into the secondary purified solution for acidification, then chloroform is used for extraction, reduced pressure distillation is carried out for solvent separation, and then bilirubin is obtained.By means of the method, metal mercury in bilirubin can be effectively removed, the mercury content is controlled not to exceed 0.2 mg / Kg, and meanwhile the yield of bilirubin is guaranteed.

Description

Technical Field

[0001] This invention relates to the field of bilirubin preparation technology, and in particular to a method for removing mercury from bilirubin. Background Technology

[0002] Bilirubin, extracted from animal bile, is a crucial raw material for the preparation of artificial bezoar. Currently, the problem of excessive mercury content in artificially extracted bilirubin products is quite serious. Due to bioaccumulation, animals have high mercury levels. In the extraction process of bilirubin from animal bile, most of the mercury remains in the bilirubin product, leading to excessive mercury content. According to the 2025 edition of the Chinese Pharmacopoeia, the limit for mercury residue in general pharmaceuticals should not exceed 0.2 mg / kg. Existing technologies do not disclose methods for removing mercury from bilirubin-related products. Methods for removing mercury from water typically employ chemical precipitation and activated carbon adsorption, which are not directly applicable to removing mercury from bilirubin products. Summary of the Invention

[0003] The purpose of this invention is to solve the technical problem of excessive bilirubin mercury content and to provide a method for removing bilirubin mercury.

[0004] The specific solution is a method for removing mercury from bilirubin, which includes the following steps:

[0005] 1) Prepare an aqueous solution of sodium bilirubin from calcium bilirubin salt or crude bilirubin; 2) Activated carbon is added to the sodium bilirubin aqueous solution for primary adsorption. After solid-liquid separation, a primary purified solution and primary adsorption activated carbon are obtained. 3) The primary purification solution is diluted with water, then activated carbon is added for secondary adsorption, and the secondary purification solution is obtained after solid-liquid separation. 4) The secondary purified solution is acidified with hydrochloric acid, then extracted with chloroform, and the solvent is separated by vacuum distillation to obtain bilirubin.

[0006] 2. The method for removing mercury from bilirubin according to claim 1, characterized in that, in step 1), the concentration of sodium bilirubin solution is 10-20 g / L.

[0007] Furthermore, in step 3), the purified solution is diluted to 5-10 g / L.

[0008] Furthermore, in step 2), the amount of activated carbon added during the first adsorption is 5% of the mass of the sodium bilirubin aqueous solution.

[0009] Furthermore, in step 3), the amount of activated carbon added during the secondary adsorption is 2% of the mass of the sodium bilirubin aqueous solution.

[0010] Further, in step 1), after reacting animal bile with saturated lime water, the precipitate is separated to obtain bilirubin calcium salt. After reacting bilirubin calcium salt with hydrochloric acid, sodium hydroxide aqueous solution is added to react and obtain sodium bilirubin aqueous solution.

[0011] Furthermore, in step 1), crude bilirubin is reacted with an aqueous sodium hydroxide solution to obtain an aqueous bilirubin sodium solution.

[0012] Furthermore, in step 2), the primary adsorption activated carbon produced after solid-liquid separation is eluted with deionized water, and the resulting wash water is used to dilute the primary purification solution in step 3).

[0013] After activation treatment, activated carbon develops a well-developed porous structure and contains organic functional groups such as carboxylic acid groups, hydroxyl groups, and carbonyl groups on its surface. Activated carbon is widely used in wastewater treatment, effectively adsorbing and removing heavy metal ions and organic matter from water. The adsorption of activated carbon includes physical adsorption and chemical adsorption; it can form stable chemical adsorption on organic matter and metal cations.

[0014] This invention converts bilirubin or bilirubin calcium into sodium bilirubin, and then uses activated carbon to remove mercury from the sodium bilirubin solution. The process involves two activated carbon adsorption processes: first, an excess of activated carbon is used to adsorb the high-concentration sodium bilirubin solution, and second, a small amount of activated carbon is used to adsorb the low-concentration sodium bilirubin solution, thereby improving the mercury removal effect while reducing bilirubin loss.

[0015] The advantage of this invention is that it can effectively remove metallic mercury from bilirubin, control the mercury content to no more than 0.2 mg / kg, and at the same time ensure the yield of bilirubin. Detailed Implementation

[0016] The present invention will be further described below with reference to specific embodiments. The illustrative embodiments and descriptions herein are used to explain the present invention, but are not intended to limit the present invention.

[0017] Example 1 10 kg of pig bile was mixed with 0.5 wt% sodium bisulfite and 15 L of saturated lime water. The mixture was filtered to obtain 4.5 g of precipitate. A suitable amount of water was added to form a paste. Another 0.5 wt% sodium bisulfite was added, and the mixture was acidified with dilute hydrochloric acid to adjust the pH to 2-3. Then, 20% sodium hydroxide solution was added to adjust the pH to 7-8, and the solution was diluted with water to 300 ml. 5% activated carbon granules were added and stirred for 2 hours. The activated carbon was separated by filtration. The filtrate was diluted with water to 500 ml, and then 2% activated carbon was added and stirred for 2 hours. The activated carbon was separated by filtration. The filtrate was acidified with hydrochloric acid to adjust the pH to 2-3. Chloroform extraction was performed to separate the lower organic phase. The mixture was distilled under reduced pressure to obtain crystals, which were dried at 50 °C to obtain 3.8 g of bilirubin product. The mercury content was determined to be 0.12 mg / kg.

[0018] Example 2 10 kg of pig bile was mixed with 0.5 wt% sodium bisulfite and 15 L of saturated lime water. The mixture was filtered to obtain 5.0 g of precipitate. A suitable amount of water was added to form a paste. 0.5 wt% sodium bisulfite was added, and the mixture was acidified with dilute hydrochloric acid to adjust the pH to 2-3. Then, 20% sodium hydroxide solution was added to adjust the pH to 7-8, and the mixture was diluted with water to 200 ml. 5% activated carbon granules were added and stirred for 2 hours. The activated carbon was separated by filtration. The activated carbon was washed with 300 ml of water, and the resulting washings were mixed with the filtrate and diluted with water to 500 ml. 2% activated carbon was added and stirred for 2 hours. The activated carbon was separated by filtration. The filtrate was acidified with hydrochloric acid to adjust the pH to 2-3. Chloroform was added for extraction, and the lower organic phase was separated. The mixture was distilled under reduced pressure to obtain crystals, which were dried at 50 °C to obtain 4.8 g of bilirubin product. The mercury content was determined to be 0.18 mg / kg.

[0019] Example 3 Add 5g of crude bilirubin to an appropriate amount of water to adjust to a paste consistency. Add 0.5wt% sodium bisulfite and then 20% sodium hydroxide solution to adjust the pH to 7-8. Dilute with water to 200ml. Add 2% activated carbon and stir for 2 hours. Filter to separate the activated carbon. Elute the activated carbon with 300ml of water. Mix the resulting washings with the filtrate and dilute with water to 500ml. Add another 2% activated carbon and stir. Filter to separate the activated carbon. Acidify the filtrate with hydrochloric acid and adjust the pH to 2-3. Extract with chloroform, separate the lower organic phase, distill under reduced pressure to obtain crystals, and dry at 50℃ to obtain 4.6g of bilirubin product. The mercury content is determined to be 0.11mg / Kg.

[0020] Comparative Example 1 10 kg of pig bile was mixed with 0.5% sodium bisulfite and 5% activated carbon for 2 hours, filtered, and 15 L of saturated lime water was added. After filtration, 4.5 g of precipitate was obtained. The precipitate was mixed with an appropriate amount of water to form a paste, 0.5 wt% sodium bisulfite was added, and the mixture was acidified with dilute hydrochloric acid to adjust the pH to 2-3. Chloroform was added for extraction, the lower organic phase was separated, and the mixture was distilled under reduced pressure to obtain crystals. The crystals were dried at 50 °C to obtain 3.5 g of bilirubin product, with a mercury content of 0.69 mg / kg.

[0021] Comparative Example 2 10 kg of pig bile was mixed with 0.5% sodium bisulfite and 15 L of saturated lime water. The mixture was filtered to obtain 4.5 g of precipitate. The precipitate was mixed with an appropriate amount of water to form a paste. 0.5 wt% sodium bisulfite was added, and the mixture was acidified with dilute hydrochloric acid to adjust the pH to 2-3. Chloroform was added for extraction, and the lower organic phase was separated. The mixture was then distilled under reduced pressure to obtain crystals. The crystals were dried at 50 °C to obtain 5.2 g of bilirubin product. The mercury content was determined to be 2.13 mg / kg.

[0022] Comparative Example 3 5g of crude bilirubin was dissolved in 300ml of chloroform, 2% activated carbon was added and stirred, filtered, and distilled under reduced pressure to obtain crystals. The crystals were dried at 50℃ to obtain 2.2g of bilirubin product, with a mercury content of 0.15mg / Kg.

[0023] The bilirubin products obtained in the above examples and comparative examples were subjected to mercury content determination by cold atomic absorption spectrometry.

[0024] The comparison shows that the bilirubin mercury content obtained in Examples 1-3 is less than 0.2 mg / kg, while the mercury content in Comparative Examples 1 and 2 is higher. Furthermore, the bilirubin yield in Example 1 is 0.0038%, and the bilirubin yield in Example 2 is 0.0048%. By recovering the wash water from the primary activated carbon, the bilirubin yield can be improved without a significant increase in mercury content.

[0025] The bilirubin mercury content obtained in Comparative Examples 1 and 2 exceeded the standard, and the bilirubin yield loss in Comparative Example 3 was too high compared with Example 3.

Claims

1. A method for removing mercury from bilirubin, characterized in that, Includes the following steps: 1) Prepare an aqueous solution of sodium bilirubin from calcium bilirubin salt or crude bilirubin; 2) Activated carbon is added to the sodium bilirubin aqueous solution for primary adsorption. After solid-liquid separation, a primary purified solution and primary adsorption activated carbon are obtained. 3) The primary purification solution is diluted with water, then activated carbon is added for secondary adsorption, and the secondary purification solution is obtained after solid-liquid separation. 4) The secondary purified solution is acidified with hydrochloric acid, then extracted with chloroform, and the solvent is separated by vacuum distillation to obtain bilirubin.

2. The method for removing mercury from bilirubin according to claim 1, characterized in that, In step 1), the concentration of sodium bilirubin solution is 10-20 g / L.

3. The method for removing mercury from bilirubin according to claim 1, characterized in that, In step 3), the purified solution is diluted to 5-10 g / L.

4. The method for removing mercury from bilirubin according to claim 1, characterized in that, In step 2), the amount of activated carbon added during the first adsorption is 5% of the mass of the sodium bilirubin aqueous solution.

5. The method for removing mercury from bilirubin according to claim 1, characterized in that, In step 3), the amount of activated carbon added during the secondary adsorption is 2% of the mass of the sodium bilirubin aqueous solution.

6. The method for removing mercury from bilirubin according to claim 1, characterized in that, In step 1), animal bile is reacted with saturated lime water, and the precipitate is separated to obtain bilirubin calcium salt. After the bilirubin calcium salt is reacted with hydrochloric acid, sodium hydroxide aqueous solution is added to react and obtain sodium bilirubin aqueous solution.

7. The method for removing mercury from bilirubin according to claim 1, characterized in that, In step 1), crude bilirubin is reacted with an aqueous sodium hydroxide solution to obtain an aqueous bilirubin sodium solution.

8. The method for removing mercury from bilirubin according to claim 1, characterized in that, In step 2), the primary adsorption activated carbon produced after solid-liquid separation is eluted with deionized water, and the resulting wash water is used to dilute the primary purification solution in step 3).