Preparation method of pharmaceutical-grade high-purity lithium carbonate

Abstract

The invention belongs to the field of preparation of medical materials, and particularly relates to a preparation method of medical-grade high-purity lithium carbonate, which comprises the following steps: carrying out replacement reaction on metal lithium and deionized water to prepare a lithium hydroxide solution; introducing carbon dioxide gas into the lithium hydroxide solution, carrying out carbonization treatment, controlling the pH at the end point of the carbonization reaction to be 8-10.5, and then carrying out solid-liquid separation treatment to obtain a lithium bicarbonate solution; carrying out heat preservation treatment on the lithium bicarbonate solution at the temperature T and the pressure P, and separating to obtain pharmaceutical-grade high-purity lithium carbonate; the temperature T ranges from 90 DEG C to 98 DEG C, and the P ranges from 0.01 Mpa to 0.09 Mpa. According to the method, lithium carbonate is synthesized by utilizing a reaction mechanism of replacement-carbonization and thermal insulation transformation treatment, and on the basis, the combination of the pH value of carbonization and the temperature T and pressure P of thermal insulation treatment is further matched, so that the nucleation behavior of lithium carbonate can be accidentally controlled, the nucleation wrapping of impurities is reduced, and the purity of lithium carbonate is improved. Therefore, lithium carbonate which meets medical application requirements and has excellent particle size uniformity can be prepared with high direct yield based on a simple means.

Description

Technical Field

[0001] The present invention relates to the field of preparation of pharmaceutical grade high-purity lithium carbonate, and in particular to a method for preparing pharmaceutical grade high-purity lithium carbonate. Background Art

[0002] Lithium carbonate is an inorganic compound that is widely used in industry and also plays an important role in the medical field. Pharmaceutical grade lithium carbonate is mainly used to treat mental illnesses such as bipolar disorder. It relieves patients' manic and depressive symptoms by regulating neurotransmitters and stabilizing emotions. Its mechanism of action is relatively complex and can affect a variety of neurochemical processes. Pharmaceutical grade lithium carbonate has extremely high purity requirements and the impurity content must be strictly controlled to ensure drug safety.

[0003] At present, pharmaceutical-grade high-purity lithium carbonate is mainly prepared with battery-grade lithium carbonate as raw material. Battery-grade lithium carbonate contains monovalent, divalent and above metal ions, as well as anions such as sulfate and chloride ions, with the main content being above 99.5%. First, battery-grade lithium carbonate is reacted with hydrochloric acid to obtain a lithium chloride solution, which is then subjected to solvent extraction and sulfuric acid stripping to obtain a high-purity lithium sulfate solution, and the high-purity lithium sulfate solution is reacted with high-purity sodium carbonate to obtain a high-purity lithium carbonate wet material, which is then dried and crushed to obtain pharmaceutical-grade high-purity lithium carbonate; this process uses an organic solvent for extraction, resulting in an excessively high content of organic matter in the product, and a high content of sulfate, making it difficult to obtain high-purity sodium carbonate. Second, battery-grade lithium carbonate is reacted with carbon dioxide to obtain a lithium bicarbonate solution, and then EDTA is added to complex metal ions, and then pyrolysis is performed to obtain pharmaceutical-grade high-purity lithium carbonate; this process uses EDTA as a decontamination agent, resulting in a high amount of EDTA residue in the product, and an additional process is required to remove EDTA. The third is to react battery-grade lithium carbonate with carbon dioxide to obtain lithium bicarbonate solution, then use lithium-based exchange resin to remove other impurity ions, and then obtain pharmaceutical-grade high-purity lithium carbonate (such as US6048507A, CN105366695A, etc.) by pyrolysis; the lithium-based exchange resin used in this process is expensive and needs to be regenerated many times during use, resulting in a decrease in the exchange capacity of the resin. Therefore, it is of great significance to develop a method for preparing pharmaceutical-grade high-purity lithium carbonate with a simple process flow and low product impurity content. Summary of the invention

[0004] The technical problem to be solved by the present invention is to overcome the deficiencies and defects mentioned in the above background technology and provide a method for preparing pharmaceutical grade high-purity lithium carbonate with a simple process flow and low impurity content in the product.

[0005] The idea of ​​preparing lithium carbonate is relatively mature, but the existing technologies are difficult to prepare lithium carbonate that meets the requirements of medical use based on simple direct preparation methods. Most of them need to rely on complicated purification processes. Although complicated purification can optimize the purity of the product, it will increase the introduction of organic impurities, increase lithium carbonate process loss, affect the particle size homogenization rate and other new problems. In view of this problem, the present invention aims to provide a solution for directly synthesizing lithium carbonate that meets medical grade, and the technology is as follows:

[0006] A method for preparing pharmaceutical-grade high-purity lithium carbonate comprises the steps of performing a replacement reaction on metallic lithium and deionized water to obtain a lithium hydroxide solution; introducing carbon dioxide gas into the lithium hydroxide solution to perform a carbonization treatment, controlling the pH value at the end point of the carbonization reaction to be 8 to 10.5, and then performing a solid-liquid separation treatment to obtain a lithium bicarbonate solution; and then performing a heat preservation treatment on the lithium bicarbonate solution at a temperature T and a pressure P to separate and obtain pharmaceutical-grade high-purity lithium carbonate;

[0007] The temperature T is 90-98° C., and P is 0.01-0.09 MPa.

[0008] The present invention utilizes the reaction mechanism of substitution-carbonization and heat preservation transformation treatment to synthesize lithium carbonate. On this basis, the pH of carbonization, the temperature T of heat preservation treatment and the pressure P are further coordinated, so that the nucleation behavior of lithium carbonate can be unexpectedly controlled, and the nucleation encapsulation of impurities can be reduced. In this way, lithium carbonate that meets the requirements of medical applications and has excellent particle size uniformity can be prepared with a high direct yield based on simple means. The scheme described in the present invention is different from the conventional idea of ​​preparing medical lithium carbonate. It is based on the joint control of reaction mechanism and process conditions. Under the premise of significantly simplifying the process and raw material types, high-quality medical lithium carbonate that meets the requirements of medical high purity, high yield, particle size, etc. can be prepared without complicated purification.

[0009] In the present invention, the content of metallic lithium is ≥99.95%.

[0010] In the present invention, a protective atmosphere is used to replace the air in the reaction chamber before the replacement reaction. The protective atmosphere is, for example, nitrogen, an inert gas, etc.

[0011] In the present invention, the conductivity of deionized water is ≤0.5us / cm.

[0012] In the present invention, the deionized water may also be preliminarily treated by bubbling with a protective atmosphere.

[0013] In the present invention, the amount of deionized water added is more than 5 times the weight of the metal lithium. Considering the preparation efficiency and cost, it can be further more than 10 times, and further can be 10 to 25 times.

[0014] In the present invention, the temperature of the replacement reaction is controlled below 5°C, and can further be 0 to 5°C.

[0015] In the present invention, metallic lithium can be placed in a reaction container in advance, and the air therein can be replaced with a protective atmosphere in advance, and then the deionized water can be added to the reaction container to perform a replacement reaction. The flow rate of the deionized water can be, for example, 0.5 to 100 L / h, and further can be 1 to 55 L / h.

[0016] In the present invention, the purity of carbon dioxide gas is ≥99.99%;

[0017] The speed of carbon dioxide gas introduction is 5~200m 3 / h, and can be further 10 to 100 m 3 / h.

[0018] In the present invention, the carbonization reaction temperature is 10-30°C.

[0019] In the present invention, carbon dioxide is introduced to carry out carbonization treatment, and the pH of the system is preferably controlled to be 8-10.

[0020] In the present invention, the heat preservation treatment time at the temperature T and the pressure P is 1 to 5 hours, and can further be 2 to 3 hours.

[0021] In the present invention, the main content of medical grade high-purity lithium carbonate is ≥99.995%, and the total amount of impurity ions is ≤50ppm.

[0022] Beneficial Effects

[0023] The present invention provides a method for preparing medical grade high-purity lithium carbonate. The method uses metal lithium discs commonly used in industry as raw materials, does not use organic solvents and other high-purity inorganic salts, and can obtain medical grade high-purity lithium carbonate with extremely low impurity content after being treated with deionized water and high-purity carbon dioxide. The chemical equation for the reaction of metal lithium discs and water is shown in (1). In order to control the reaction speed, deionized water is slowly added to the metal lithium discs and the reaction is carried out at low temperature. The hydrogen obtained by the reaction can be compressed and sold as a product.

[0024] 2 Li+2 H 2 O=2LiOH+H 2 ↑ (1)

[0025] High-purity carbon dioxide gas is introduced into the lithium hydroxide solution to produce a chemical reaction. After precision filtration, a high-purity lithium bicarbonate solution can be obtained. The chemical equation is shown in (2).

[0026] LiOH+CO 2 =LiHCO 3 (2)

[0027] The high-purity lithium bicarbonate solution is heat-insulated at the temperature T and pressure P, so that the overflow rate of carbon dioxide can be controlled, the lithium carbonate crystallization is more complete, and the impurity wrapping phenomenon can be effectively avoided. At the same time, the particle size of lithium carbonate is controlled and its dispersibility in the solution is improved. After drying, medical grade high-purity lithium carbonate can be obtained. The chemical equation is shown in (3).

[0028] 2 LiHCO 3 =Li 2 CO 3 +H 2 O+CO 2 ↑ (3)

[0029] Compared with the traditional preparation method, the preparation method does not use other organic and inorganic raw materials except deionized water and high-purity carbon dioxide, which can well avoid the introduction of impurities, has a simple process flow, low impurity content in the product, and is easy to realize industrialization. In addition, the preparation method of the present invention can directly prepare medical-grade lithium carbonate with high yield, and the prepared medical-grade lithium carbonate has high particle size uniformity. DETAILED DESCRIPTION

[0030] Unless otherwise defined, all the professional terms used below have the same meanings as those generally understood by those skilled in the art. The professional terms used herein are only for the purpose of describing specific embodiments and are not intended to limit the scope of protection of the present invention.

[0031] Unless otherwise specified, various raw materials, reagents, instruments and equipment used in the present invention can be purchased from the market or prepared by existing methods.

[0032] An optional method for preparing pharmaceutical grade high-purity lithium carbonate of the present invention comprises the following steps:

[0033] (1) adding a certain amount of lithium metal discs into a reactor, and introducing protective gas to replace the air in the reactor;

[0034] (2) slowly adding a certain amount of deionized water into the reactor, placing the reactor in a cold water bath at a certain temperature to control the reaction rate, and collecting the gas obtained by the reaction, thereby obtaining solution A;

[0035] (3) introducing high-purity carbon dioxide gas into the fully reacted solution A, maintaining a certain reaction temperature, and after reaching a certain pH value, obtaining solution B after precise filtration;

[0036] (4) Solution B is reacted at a certain temperature T and pressure P to obtain carbon dioxide gas and solution C containing lithium carbonate. Solution C is filtered to obtain wet lithium carbonate, which is then dried to obtain pharmaceutical grade high-purity lithium carbonate.

[0037] In the above preparation method, preferably, the main content of metallic lithium in step (1) is ≥99.95%;

[0038] In the above preparation method, preferably, the protective gas in step (1) is one of argon and nitrogen;

[0039] In the above preparation method, preferably, the conductivity of the deionized water in step (2) is ≤0.5 us / cm, the amount of deionized water added is more than 5 times the weight of the metal lithium disc, and can be more than 10 times, and can be 10 to 25 times, and the addition rate is 0.5 to 100 L / h;

[0040] In the above preparation method, preferably, the temperature of the cold water bath in step (2) is 0-5°C;

[0041] In the above-mentioned preparation method, preferably, the purity of the carbon dioxide gas in step (3) is ≥99.95% and the introduction speed of the carbon dioxide gas is 5 to 200 m / s. 3 / h, reaction temperature is 10-30°C, pH value is 8-10;

[0042] In the above-mentioned preparation method, the reaction temperature in step (4) is 90-98° C., and the pressure is 0.01-0.09 MPa;

[0043] In the above preparation method, preferably, in step (4), the main content of the pharmaceutical grade high-purity lithium carbonate is ≥99.995%, and the total amount of impurity ions is ≤50ppm;

[0044] Embodiment 1:

[0045] Add 20g of metallic lithium discs (main content 99.99%) into the reactor, and introduce argon as a protective gas to replace the air in the reactor. Add 240g of deionized water (conductivity 0.1us / cm) into the reactor at a rate of 1L / h, and place the reactor in a cold water bath at 0℃. When no gas is released from the reactor, the reaction is determined to be complete, and a lithium hydroxide solution is obtained. Add 10m 3 / h rate of high-purity carbon dioxide gas (content 99.99%), maintain the reaction temperature at 20 ° C, until the pH of the solution is 8, after passing through a precision filter to obtain a high-purity lithium bicarbonate solution. The high-purity lithium carbonate solution was heated to 95 ° C, the pressure P was 0.01Mpa, and lithium carbonate solids continued to appear. After reacting for 2 hours, it was filtered and dried in a 120 ° C oven to obtain 95.23g of medical grade high-purity lithium carbonate, with a total impurity content of 8.41ppm, D10~D90 of 4.4um~7.8um, uniform particle size distribution, and component analysis as shown in Table 1.

[0046] Table 1 Chemical composition analysis of preparation of pharmaceutical grade high purity lithium carbonate in Example 1 (unit: ppm)

[0047]

[0048] Embodiment 2:

[0049] Add 20g of metallic lithium discs (main content 99.95%) into the reactor, and introduce argon as a protective gas to replace the air in the reactor. Add 300g of deionized water (conductivity 0.5us / cm) into the reactor at a rate of 50L / h, and place the reactor in a cold water bath at 5°C. When no gas is released from the reactor, the reaction is determined to be complete, and a lithium hydroxide solution is obtained. Add 100m 3 / h rate of high-purity carbon dioxide gas (content 99.95%), maintain the reaction temperature at 30 ° C, until the pH of the solution is 10, after passing through a precision filter to obtain a high-purity lithium bicarbonate solution. The high-purity lithium carbonate solution was heated to 90 ° C, the pressure was 0.09Mpa, and lithium carbonate solids continued to appear. After reacting for 2 hours, it was filtered and dried in a 120 ° C oven to obtain 94.45g of medical grade high-purity lithium carbonate, with a total impurity content of 46.10ppm, D10~D90 of 4.2um~8.5um, uniform particle size distribution, and component analysis as shown in Table 2.

[0050] Table 2 Chemical composition analysis of preparation of pharmaceutical grade high purity lithium carbonate in Example 2 (unit: ppm)

[0051]

[0052]

[0053] Comparative Example 1

[0054] The other conditions were the same as those in Example 1. The pH value of the solution was controlled to be 11, the pressure P was normal pressure, and 82.34 g of medical grade lithium carbonate was obtained. The yield was reduced, D10-D90 was 2.8-10.7 um, the particle size distribution range was widened, the uniformity was reduced, and the component analysis was shown in Table 3.

[0055] Table 3 Chemical composition analysis of pharmaceutical grade high purity lithium carbonate prepared in Comparative Example 1 (unit: ppm)

[0056]

[0057] It can be seen from Example 1 and Comparative Example 1 that by adopting the preparation principle of the present invention and jointly controlling the pH and pressure in the reaction stage, medical grade lithium carbonate can be unexpectedly obtained. Not only that, the yield and particle size distribution of medical grade lithium carbonate can also be improved, which is conducive to obtaining better quality medical grade lithium carbonate.

Claims

1. A method for preparing pharmaceutical grade high-purity lithium carbonate, characterized in that: The lithium hydroxide solution is prepared by carrying out a replacement reaction between metallic lithium and deionized water; carbon dioxide gas is introduced into the lithium hydroxide solution for carbonization treatment, and the pH value at the end point of the carbonization reaction is controlled to be 8-10.5, followed by solid-liquid separation treatment to obtain a lithium bicarbonate solution; the lithium bicarbonate solution is then heat-insulated at a temperature T and a pressure P to separate and obtain pharmaceutical-grade high-purity lithium carbonate; The temperature T is 90-98° C., and P is 0.01-0.09 MPa.

2. The method for preparing pharmaceutical grade high-purity lithium carbonate according to claim 1, characterized in that: The content of metallic lithium is ≥99.95%.

3. The method for preparing pharmaceutical grade high-purity lithium carbonate according to claim 1, characterized in that: Before the replacement reaction, the air in the reaction chamber is replaced with a protective atmosphere.

4. The method for preparing pharmaceutical grade high-purity lithium carbonate according to claim 1, characterized in that: The conductivity of deionized water is ≤0.5 us / cm.

5. The method for preparing pharmaceutical grade high-purity lithium carbonate according to claim 1, characterized in that: The amount of deionized water added is more than 5 times the weight of the metallic lithium, preferably 10 to 25 times, and the addition rate is 0.5 to 100 L / h.

6. The method for preparing pharmaceutical grade high-purity lithium carbonate according to claim 1, characterized in that: The temperature of the replacement reaction was controlled below 5°C.

7. The method for preparing pharmaceutical grade high-purity lithium carbonate according to claim 1, characterized in that: The purity of carbon dioxide gas is ≥99.95%; The speed of carbon dioxide gas introduction is 5~200 m 3 / h.

8. The method for preparing pharmaceutical grade high-purity lithium carbonate according to claim 1, characterized in that: The carbonization reaction temperature is 10~30℃.

9. The method for preparing pharmaceutical grade high-purity lithium carbonate according to claim 1, characterized in that: The insulation treatment time at temperature T and pressure P is 1~5h.

10. The method for preparing pharmaceutical grade high-purity lithium carbonate according to any one of claims 1 to 9, characterized in that: The main content of medical grade high purity lithium carbonate is ≥99.995%, and the total impurity ions are ≤50ppm.

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