Preparation method of nanoscale bismuth subnitrate

Abstract

The application discloses a preparation method of nanometer bismuth subnitrate, and belongs to the technical field of bismuth subnitrate preparation. The method is to prepare bismuth nitrate solution from crude bismuth oxide, and non-reactive gas is introduced into the bismuth nitrate solution during hydrolysis to form microbubbles to promote the formation of uniform bismuth subnitrate crystal nucleus; and the bismuth subnitrate crystal nucleus is dispersed by ball milling during growth to promote the uniform growth of the bismuth subnitrate crystal nucleus into nanometer bismuth subnitrate. The method uses bismuth oxide as raw material, avoids the generation of toxic NOx gas, is simple in operation, and has mild conditions, and can meet large-scale industrial production. In particular, the prepared bismuth subnitrate product is nanometer, has a spherical shape, a particle size of 60-100 nm, and a purity of greater than or equal to 99.9%, and fully meets the requirements of medicinal nanometer bismuth subnitrate.

Description

Technical Field

[0001] This invention relates to a method for preparing bismuth subnitrate, and particularly to a method for preparing nano-sized bismuth subnitrate, belonging to the field of bismuth subnitrate preparation technology. Background Technology

[0002] Bismuth is primarily used in industry to manufacture low-melting-point alloys and is widely applied in fire protection and electrical safety devices. It is also used in lead-free pigments, electronic ceramics, semiconductor components, and chemical catalysts. In the pharmaceutical field, bismuth compounds such as bismuth subnitrate, being insoluble in water, are not absorbed by the gastrointestinal tract and have protective effects on the gastrointestinal mucosa and astringent and antidiarrheal properties, making them a key raw material for stomach medicines. For example, bismuth subnitrate tablets are used in gastroenterology, primarily for treating peptic ulcers, enteritis, and diarrhea. The traditional wet process for producing bismuth subnitrate involves directly reacting metallic bismuth with concentrated nitric acid to produce the intermediate product bismuth nitrate, which is then used as a raw material to prepare the final product via pure water hydrolysis or neutralization hydrolysis. Existing methods require the initial preparation of a bismuth nitrate solution, which generates toxic NOx gas and consumes large quantities of nitric acid during the dissolution of metallic bismuth, while also producing large amounts of dilute nitric acid and ammonium nitrate wastewater. In addition, there is also literature (“A process for preparing bismuth subnitrate from bismuth oxide by liquid-phase ball milling”, Xia Jiyong et al., Journal of Central South University (Natural Science Edition), Vol. 46, No. 2, February 2015) reporting a new process for preparing bismuth subnitrate from Bi2O3 powder by wet ball milling. However, the bismuth subnitrate prepared by this method mainly has a rod-like morphology, with a grain size of about 10 μm, which is difficult to meet the requirements of pharmaceutical-grade nano-sized bismuth subnitrate. Nano-sized bismuth subnitrate has advantages such as good dispersibility, high solubility and bioavailability when formulated. In particular, nano-sizing can significantly increase the specific surface area (a 10-fold reduction in particle size increases the surface area by about 100 times), significantly improving the dissolution rate and absorption efficiency of hydrophobic drugs. Summary of the Invention

[0003] To address the shortcomings of existing technologies, the present invention aims to provide a method for preparing nano-sized bismuth subnitrate. This method uses bismuth oxide as a raw material, avoids the generation of toxic NOx gas, and is simple to operate under mild conditions, meeting the requirements for large-scale industrial production. In particular, the prepared bismuth subnitrate product is nano-sized, with a spherical morphology, a particle size of 60~100nm, and a purity of ≥99.9%, fully meeting the requirements for pharmaceutical-grade nano-sized bismuth subnitrate.

[0004] To achieve the above-mentioned technical objectives, the present invention provides a method for preparing nano-sized bismuth subnitrate, which includes the following steps:

[0005] S1: Dissolve crude bismuth oxide in concentrated nitric acid, filter, and obtain bismuth nitrate solution;

[0006] S2: Add water to the bismuth nitrate solution, and at the same time introduce a non-reactive gas into the bottom of the bismuth nitrate solution to form microbubbles, so that the bismuth nitrate undergoes a hydrolysis reaction to generate bismuth subnitrate crystal nuclei;

[0007] S3: Add grinding media and dispersant to the solution in which bismuth subnitrate nuclei are generated and ball mill to promote uniform growth of bismuth subnitrate nuclei, and obtain nano bismuth subnitrate dispersion;

[0008] S4: After separating the nano-bismuth subnitrate dispersion from the ball milling media, wash and dry to obtain nano-sized bismuth subnitrate.

[0009] The key to preparing nanoscale bismuth hyponitrate using crude bismuth oxide in this invention lies in controlling the formation and growth process of bismuth hyponitrate nuclei to obtain uniform, spherical nanoscale bismuth hyponitrate. More specifically, during the hydrolysis of bismuth nitrate, a gaseous medium is introduced to form microbubbles through bubbling. These microbubbles promote the uniform generation of a large number of bismuth hyponitrate nuclei. During the growth of the bismuth hyponitrate nuclei, the synergistic effect of the ball milling media and the dispersant is utilized. The mechanical action of the ball milling media prevents physical agglomeration between the bismuth hyponitrate nuclei, while the dispersant improves the hydrophilicity of the bismuth hyponitrate nuclei through adsorption and coating, thus promoting their dispersion. This forces the bismuth hyponitrate nuclei to form highly dispersed nanocrystals through chemical growth.

[0010] This invention utilizes crude bismuth oxide to prepare nano-sized bismuth hyponitrate, thereby removing impurities from the crude bismuth oxide to obtain a high-purity nano-sized bismuth hyponitrate product. The crude bismuth oxide is dissolved in concentrated nitric acid and filtered to remove insoluble impurities, while soluble impurities are enriched in the solution during the crystallization of bismuth hyponitrate, thus yielding a nano-sized bismuth hyponitrate product with a purity ≥99.9%.

[0011] As a preferred embodiment, the mass-to-volume ratio of crude bismuth oxide to concentrated nitric acid is 3 kg:1 L to 1 kg:1 L. By adding sufficient concentrated nitric acid, the crude bismuth oxide can be completely dissolved and converted into bismuth nitrate.

[0012] As a preferred embodiment, the volume ratio of the bismuth nitrate solution to water is 1:3 to 1:8. By controlling the amount of water added, the bismuth nitrate solution can be diluted to a suitable pH range, which is beneficial for controlling the hydrolysis rate of bismuth nitrate.

[0013] As a preferred embodiment, the introduction rate of the non-reactive gas is 5~15 L / min. The introduction rate of the non-reactive gas mainly affects the formation process of bismuth subnitrate crystal nuclei. If the introduction rate of the non-reactive gas is too slow, it will cause the bismuth subnitrate crystal nuclei to agglomerate, making it difficult to obtain uniformly dispersed crystal nuclei. If the introduction rate of the non-reactive gas is too fast, it will cause the solution system to boil violently.

[0014] As a preferred embodiment, the non-reactive gas includes at least one of nitrogen and an inert gas. Inert gases include, for example, argon and helium. A microbubble generator can be used to promote microbubble formation during the introduction of the non-reactive gas.

[0015] As a preferred embodiment, the milling media consists of zirconia beads with a particle size distribution in the range of 0.5 to 2.0 mm. The particle size of the milling media affects the dispersibility of bismuth subnitrate nuclei. It is preferable to use milling balls with smaller particle sizes, which can promote the dispersion of bismuth subnitrate nuclei agglomerates and ensure that the bismuth subnitrate nuclei grow to a nanoscale.

[0016] As a preferred embodiment, the dispersant comprises polyethylene glycol; the amount of the dispersant added is 0.3% to 0.8% of the mass of crude bismuth oxide, and the polyethylene glycol is further preferably PEG400 to PEG1200. Specific examples include PEG400, PEG600, PEG800, PEG1200, etc. Polyethylene glycol can adsorb and coat the surface of bismuth subnitrate crystal nuclei. On the one hand, it introduces a large number of hydrophilic groups, improving its dispersibility; on the other hand, it can induce the growth of bismuth subnitrate crystals into spherical nanocrystal particles.

[0017] As a preferred embodiment, the ball milling conditions are: ball-to-material mass ratio of 5~15:1, ball milling speed of 1500~2500 r / min, and milling time of 1.5h~2.0h. Under suitable ball milling conditions, the dispersion of bismuth nitrate crystal nuclei can be enhanced through mechanical force, preventing their physical agglomeration into precipitation.

[0018] As a preferred embodiment, the pH is controlled within the range of 1.8 to 2.5 during the ball milling process. Suitable acidic conditions ensure the stability of bismuth subnitrate, which is beneficial for its crystal nucleation growth.

[0019] Compared with existing technologies, the beneficial technical effects of the present invention are as follows:

[0020] The bismuth subnitrate product prepared by this invention has nanoscale size, spherical morphology, uniform particle size distribution ranging from 60 to 100 nm, and purity ≥ 99.9%, which fully meets the requirements for pharmaceutical-grade nanoscale bismuth subnitrate.

[0021] The method for preparing bismuth subnitrate of the present invention uses bismuth oxide as raw material, which has low raw material cost and can avoid the generation of toxic NOx gas.

[0022] The method for preparing bismuth subnitrate of the present invention is simple to operate, has mild conditions, and is suitable for large-scale industrial production. Attached Figure Description

[0023] Figure 1 The image shows a scanning electron microscope (SEM) image of the nanoscale bismuth subnitrate prepared in Example 1. Detailed Implementation

[0024] The following specific embodiments are intended to further illustrate the content of the present invention, rather than to limit the scope of protection of the claims of the present invention.

[0025] The crude bismuth oxide raw material used in the following examples is an industrial-grade commercial raw material with a purity of 92.0% and main impurities of Fe 2.1%, Si 2.5%, Sb 1.6%, and Ga 1.3%.

[0026] Example 1

[0027] S1: Dissolve crude bismuth oxide (30g) in concentrated nitric acid (10mL), filter, and obtain bismuth nitrate solution.

[0028] S2: Add water (50 mL) to the bismuth nitrate solution, and at the same time, introduce nitrogen gas into the bottom of the bismuth nitrate solution. The nitrogen gas forms microbubbles through the distributor. The nitrogen gas introduction rate is controlled at 10 L / min, so that the bismuth nitrate undergoes a hydrolysis reaction to generate bismuth subnitrate crystal nuclei. The reaction time is 1.5 h.

[0029] S3: Adjust the pH of the solution for generating bismuth subnitrate crystal nuclei to 2.0, add zirconia beads with a particle size distribution of 0.5~2mm, with a ball-to-material ratio of 10:1, and simultaneously add polyethylene glycol 400 (0.15g) dispersant for ball milling at a speed of 2000r / min for 1.5h to promote uniform growth of bismuth subnitrate crystal nuclei and obtain nano-bismuth subnitrate dispersion.

[0030] S4: After separating the nano-bismuth subnitrate dispersion by sieving and ball milling media, the solvent is removed by filtration, and the solid product is washed and dried to obtain nano-sized bismuth subnitrate.

[0031] The obtained nanoscale bismuth subnitrate scanning electron microscope results are as follows: Figure 1 As shown, it has a relatively standard spherical morphology with a uniform particle size distribution, mainly in the range of 70~100nm. Elemental analysis shows that its purity is ≥99.9%, fully meeting the requirements for pharmaceutical-grade nano-sized bismuth subnitrate. The elemental composition is: Bi 71.69%, H 0.52%, N 4.00%, O 23.78%.

[0032] Example 2

[0033] S1: Dissolve crude bismuth oxide (30g) in concentrated nitric acid (20mL), filter, and obtain bismuth nitrate solution.

[0034] S2: Add water (70 mL) to the bismuth nitrate solution, and at the same time, introduce nitrogen gas into the bottom of the bismuth nitrate solution. The nitrogen gas forms microbubbles through the distributor. The nitrogen gas introduction rate is controlled at 15 L / min, so that the bismuth nitrate undergoes a hydrolysis reaction to generate bismuth subnitrate crystal nuclei. The reaction time is 2.0 h.

[0035] S3: Adjust the pH of the solution for generating bismuth subnitrate crystal nuclei to 2.5, add zirconia beads with a particle size distribution of 0.5~2mm, with a ball-to-material ratio of 6:1, and simultaneously add polyethylene glycol 400 (0.18g) dispersant for ball milling at a speed of 2400r / min for 2.0 h to promote uniform growth of bismuth subnitrate crystal nuclei and obtain nano-bismuth subnitrate dispersion.

[0036] S4: After separating the nano-bismuth subnitrate dispersion by sieving and ball milling media, the solvent is removed by filtration, and the solid product is washed and dried to obtain nano-sized bismuth subnitrate.

[0037] The obtained nano-sized bismuth subnitrate has a standard spherical morphology and a uniform particle size distribution, mainly in the range of 60-90 nm. Elemental analysis shows that its purity is ≥99.9%, fully meeting the requirements for pharmaceutical-grade nano-sized bismuth subnitrate.

[0038] Comparative Example 1

[0039] S1: Dissolve crude bismuth oxide (30g) in concentrated nitric acid (10mL), filter, and obtain bismuth nitrate solution.

[0040] S2: Add water (50 mL) to the bismuth nitrate solution, and at the same time, introduce nitrogen gas into the bottom of the bismuth nitrate solution. The nitrogen gas forms microbubbles through the distributor. The nitrogen gas introduction rate is controlled at 10 L / min, so that the bismuth nitrate undergoes a hydrolysis reaction to generate bismuth subnitrate crystal nuclei. The reaction time is 1.5 h.

[0041] S3: Adjust the pH of the solution that generates bismuth subnitrate crystal nuclei to 2.0, add zirconia beads with a particle size distribution of 0.5~2mm, with a ball-to-material ratio of 10:1, and ball mill at a speed of 2000r / min for 1.5h to obtain a bismuth subnitrate dispersion.

[0042] S4: After separating the bismuth subnitrate dispersion by sieving and ball milling media, the solvent is removed by filtration, and the solid product is washed and dried to obtain bismuth subnitrate.

[0043] The comparative example did not include a dispersant, which resulted in the growth of bismuth subnitrate crystal nuclei into rod-shaped elongated structures, without the formation of obvious uniform nanospheres.

[0044] Comparative Example 2

[0045] S1: Dissolve crude bismuth oxide (30g) in concentrated nitric acid (10mL), filter, and obtain bismuth nitrate solution.

[0046] S2: Add water (50 mL) to the bismuth nitrate solution to cause the bismuth nitrate to undergo a hydrolysis reaction to generate bismuth subnitrate crystal nuclei. The reaction time is 1.5 h.

[0047] S3: Adjust the pH of the solution that generates bismuth subnitrate crystal nuclei to 2.0, add zirconia beads with a particle size distribution of 0.5~2mm, the ball-to-material ratio is 10:1, and simultaneously add polyethylene glycol 400 (0.15g) dispersant for ball milling at a speed of 2000r / min for 1.5h to obtain bismuth subnitrate dispersion.

[0048] S4: After separating the bismuth subnitrate dispersion by sieving and ball milling media, the solvent is removed by filtration. The solid product is washed and dried to obtain bismuth subnitrate crystals.

[0049] Because nitrogen gas was not introduced to form microbubbles during the crystal nucleation process, the bismuth subnitrate crystal nuclei partially agglomerated, resulting in uneven crystal nucleus size. The final bismuth subnitrate particles have a particle size distribution in the range of 100 nm to 1 μm, with a wide particle distribution and large particle size.

[0050] Comparative Example 3

[0051] S1: Dissolve crude bismuth oxide (30g) in concentrated nitric acid (10mL), filter, and obtain bismuth nitrate solution.

[0052] S2: Add water (50 mL) to the bismuth nitrate solution, and at the same time, introduce nitrogen gas into the bottom of the bismuth nitrate solution. The nitrogen gas forms microbubbles through the distributor. The nitrogen gas introduction rate is controlled at 10 L / min, so that the bismuth nitrate undergoes a hydrolysis reaction to generate bismuth subnitrate crystal nuclei. The reaction time is 1.5 h.

[0053] S3: Adjust the pH of the solution in which bismuth subnitrate crystal nuclei are generated to 2.0, add polyethylene glycol 400 (0.15g) dispersant and carry out conventional aging and crystallization for 1.5h to obtain bismuth subnitrate dispersion.

[0054] S4: Filter the bismuth subnitrate dispersion to remove the solvent, and wash and dry the solid product to obtain bismuth subnitrate.

[0055] Since no ball milling media were used for ball milling dispersion, the bismuth subnitrate crystal nuclei aggregated and eventually grew into spherical bismuth subnitrate particles with a particle size of 1.0~2.0μm.

Claims

1. A method for preparing nano-sized bismuth subnitrate, characterized in that: Includes the following steps: S1: Dissolve crude bismuth oxide in concentrated nitric acid, filter, and obtain bismuth nitrate solution; S2: Add water to the bismuth nitrate solution, and at the same time introduce a non-reactive gas into the bottom of the bismuth nitrate solution to form microbubbles, so that the bismuth nitrate undergoes a hydrolysis reaction to generate bismuth subnitrate crystal nuclei; S3: Add grinding media and dispersant to the solution in which bismuth subnitrate nuclei are generated and ball mill to promote uniform growth of bismuth subnitrate nuclei, and obtain nano bismuth subnitrate dispersion; S4: After separating the nano-bismuth subnitrate dispersion from the ball milling media, wash and dry to obtain nano-sized bismuth subnitrate.

2. The method for preparing nano-sized bismuth subnitrate according to claim 1, characterized in that: The mass-to-volume ratio of crude bismuth oxide to concentrated nitric acid is 3 kg:1 L to 1 kg:1 L.

3. The method for preparing nano-sized bismuth subnitrate according to claim 1, characterized in that: The volume ratio of the bismuth nitrate solution to water is 1:3 to 1:

8.

4. The method for preparing nano-sized bismuth subnitrate according to claim 1, characterized in that: The non-reactive gas is introduced at a rate of 5-15 L / min; The non-reactive gas includes at least one of nitrogen and inert gas.

5. The method for preparing nano-sized bismuth subnitrate according to claim 1, characterized in that: The ball milling media are zirconia beads with a particle size distribution in the range of 0.5~2.0 mm.

6. The method for preparing nano-sized bismuth subnitrate according to claim 1, characterized in that: The dispersant includes polyethylene glycol; The amount of dispersant added is 0.3% to 0.8% of the mass of crude bismuth oxide.

7. A method for preparing nano-sized bismuth subnitrate according to claim 1, 5, or 6, characterized in that: The ball milling conditions are as follows: ball-to-material mass ratio of 5~15:1, ball milling speed of 1500~2500 r / min, and milling time of 1.5h~2.0h.

8. The method for preparing nano-sized bismuth subnitrate according to claim 7, characterized in that: The pH is controlled within the range of 1.8 to 2.5 during the ball milling process.

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