Method for producing sucralose product with low length-diameter ratio and large crystal size by intermittent ultrasonic-assisted solventing-out crystallization method

Abstract

The invention provides an intermittent ultrasonic-assisted solvent-out crystallization process for sucralose. The intermittent ultrasonic-assisted solvent-out crystallization experiment comprises the following steps: dissolving sucralose solid in ethanol at the temperature of 15 DEG C, adding an octanoic acid anti-solvent after the sucralose solid is completely dissolved into a clear solution, uniformly mixing, and adding a small amount of high-purity sucralose as a seed crystal to initiate crystal growth. A cooling water circulating pump is started, an ultrasonic generator is put into the solution, intermittent ultrasonic crystallization is conducted on the solution at the fixed frequency and the power of 70 W, and under the conditions of the temperature, the anti-solvent ratio and the seed crystal ratio, good balance between the size and the length-diameter ratio of the sucralose crystal is achieved through the technology; the sucralose product with a low length-diameter ratio (1.244) and a large crystal size (average particle size: 42.722 [mu] m) is obtained, the thermal stability and the fluidity are better, the storage and the transportation of sucralose are facilitated, and the method has important significance on the production of high-quality sucralose.

Description

Technical Field

[0001] The present invention relates to the field of sucralose crystallization, specifically a method for controlling the morphology of sucralose based on ultrasonic crystallization technology, belonging to the technical field of sucralose production. Background Technique

[0002] Sucralose, commonly known as sucralose, is a new type of halogenated sucrose derivative processed from sucrose. Its chemical name is 4,1',6'-trichloro-4,1',6'-trideoxygalactosucrose, and its trade name is Splenda. It is a white granular, odorless, and non-hygroscopic powder with the molecular formula C 12 H 19 Cl3O8 and a molecular weight of 397.64. Among all non-nutritive sweeteners, the chemical structure of sucralose is most similar to that of sucrose (C 12 H 22 O 11 ), where three hydrogen atoms in sucrose are replaced by chlorine in sucralose (C 12 H 19 Cl3O8). Sucralose can be easily dissolved in solvents such as water, ethanol, ethyl acetate, and butyl acetate. Sucralose has a pure and fresh sweetness, and its sweetness can reach 600-700 times that of sucrose. This sweetener not only has no bitter taste, zero calories, is safe and non-toxic, but also shows excellent stability under light, high temperature, and different pH conditions. It has various health benefits, such as providing antioxidant components, assisting in weight loss, and reducing cholesterol levels, so it is widely used in industries such as food, beverage, and medicine.

[0003] Crystallization is a widely used unit operation for producing inorganic and organic compounds, drugs, cosmetics, polymers, etc. However, it is difficult to control crystal characteristics such as crystal size, morphology, polymorph, and chirality. Crystallization carried out by conventional methods (without ultrasound) usually produces crystals with a relatively large standard deviation of particle size. The use of ultrasound has been proven to greatly affect crystallization and help control crystal morphology characteristics. In the literature, Su et al. used ultrasound to change the crystallization habit of phenacetin from an irregular shape to oval particles with a relatively low aspect ratio, giving better fluidity; Zhuang Junjie et al. used ultrasound to focus on investigating the effects of ultrasound treatment time and power on the aspect ratio of sucralose. The experimental results showed that under the action of the ultrasound field, the sucralose crystals changed from needle-shaped crystals to spherical crystals, and the aspect ratio decreased significantly with the increase of treatment time and power, improving the flow performance of the product.

[0004] The mechanism of ultrasonic crystallization is that when ultrasonic waves propagate in a solution, compression and circulation will occur. During the negative pressure cycle, when the shear force exceeds the intermolecular van der Waals force of the liquid, bubbles will be generated in the solution. These bubbles will grow and eventually burst, which is called cavitation. Cavitation bubbles also form an interfacial surface area to promote primary heterogeneous nucleation. Ultrasonic waves generate cavitation in the solution, thereby increasing the mass transfer rate, shortening the induction time, reducing the width of the metastable zone, increasing the nucleation rate, and narrowing the particle size distribution. Generally speaking, if ultrasonic waves are continuously applied, the particle size will be smaller and the aspect ratio will be lower. Therefore, an intermittent ultrasonic-assisted antisolvent crystallization technology is developed. According to the characteristics of intermittent ultrasonic waves, the application of ultrasonic waves will make the particle size smaller and the aspect ratio lower. If the ultrasonic waves are removed, elastic particle sizes and aspect ratios will be generated. If ultrasonic waves are applied at certain intervals, a good balance between crystal size and aspect ratio can be achieved. So far, there has been no relevant report on the use of intermittent ultrasonic-assisted antisolvent crystallization technology in the synthesis process of sucralose. Summary of the Invention

[0005] The object of the present invention is to achieve a good balance between the crystal size and aspect ratio of sucralose crystals, obtain a sucralose product with a low aspect ratio and large crystal grain size, improve the thermal stability and fluidity, which is more conducive to the storage and transportation of sucralose, and provide theoretical guidance for the production of high-quality sucralose. The present invention provides a sucralose morphology control technology, which has a reasonable design and a simple process.

[0006] To achieve the above-mentioned invention object, the process steps of the present invention are as follows:

[0007] The first step: Dissolve sucralose solid (purity: 98%) in ethanol at a temperature of 15°C. After it is completely dissolved into a clear solution, add an antisolvent of octanoic acid (n-octanoic acid solvent as the antisolvent) and crystal seeds under molar ratio conditions. Turn on the cooling water circulation pump, and immerse an ultrasonic probe with a tip diameter of 0.5 cm into the solution from a three-necked flask. The probe is located in the center of the solution, and the solution is ultrasonically treated and mixed. During the ultrasonic process, no additional stirring equipment is required. Considering factors such as equipment use safety, high energy, and heat dissipation, use the cooling water circulation pump to keep the temperature in the water bath at 15°C, and monitor the system temperature in the sucralose crystallization solution through a thermometer. Perform intermittent ultrasonic antisolvent crystallization on it at a frequency of 22.6 kHz and a power of 70 W.

[0008] The second step: At a temperature of 15°C, turn on the ultrasonic equipment, stop the ultrasonic wave at 20 s when nucleation occurs, then let it stand for 30 min, continue ultrasonic treatment for 40 s, then let it stand for 30 min, continue ultrasonic treatment for 60 s, and then let it stand for 30 min.

[0009] Step 3: By extracting suspension samples at certain time intervals, centrifuging to separate the solid and liquid phases, drying the lower-layer solid at 50°C and -0.1 MPa, performing characterization of the sucralose product, and observing the morphology of the sucralose product and calculating the particle size distribution by field emission scanning electron microscopy (SEM).

[0010] Ultrasound generates cavitation in the solution, thereby increasing the mass transfer rate, shortening the induction time, reducing the width of the metastable zone, increasing the nucleation rate, and narrowing the particle size distribution. Generally speaking, if ultrasound is continuously applied, the particle size will be smaller and the aspect ratio will be lower. Therefore, an intermittent ultrasound-assisted antisolvent crystallization technology is developed. According to the characteristics of intermittent ultrasound, the application of ultrasound will make the particle size smaller and the aspect ratio lower. If the ultrasound is removed, elastic particle size and aspect ratio will be generated. If ultrasound is applied at certain intervals, a good balance between crystal size and aspect ratio can be achieved. So far, there has been no relevant report on the use of intermittent ultrasound-assisted antisolvent crystallization technology in the synthesis process of sucralose.

[0011] Compared with the prior art, the advantages and outstanding effects of the present invention are reflected in:

[0012] (1) In the process of controlling the morphology of sucralose, the present invention has the characteristics of fast crystallization speed, simple ultrasonic conditions, and convenient operation, and is suitable for industrial application.

[0013] (2) The crystal shape and aspect ratio of sucralose can determine its fluidity, solubility, and thermal stability. At present, sucralose has problems such as high aspect ratio and poor stability, which are extremely unfavorable for its handling and storage. By performing an intermittent ultrasound-assisted antisolvent process on sucralose, this process achieves a good balance between the crystal size and aspect ratio of sucralose, obtaining a sucralose product with a low aspect ratio (1.244) and large grain size (average particle size: 42.722 μm), which is more conducive to the storage and transportation of sucralose and is of great significance for the production of high-quality sucralose. Description of the Drawings

[0014] Figure 1 are the SEM image and particle size distribution diagram of the sucralose product in the intermittent ultrasound-assisted antisolvent process.

[0015] Figure 2 is the XRD pattern of the sucralose product.

[0016] Figure 3 is the FT-IR pattern of the sucralose product.

[0017] Figure 4 are of the 1 H-NMR patterns of the intermittent ultrasound-assisted antisolvent crystallization and commercial sucralose crystallization products.

[0018] Figure 5It is the HPLC-ELSD diagrams of the intermittent ultrasonic-assisted antisolvent crystallization and the commercial sucralose crystallization products. Detailed implementation manners

[0019] To make the content of the present invention easier to understand, the present invention will be described in detail below in conjunction with specific embodiments:

[0020] Example 1:

[0021] Intermittent ultrasonic-assisted antisolvent crystallization process: The following conditions were used for the intermittent ultrasonic-assisted antisolvent process of 0.6464 g of sucralose: antisolvent (ONA) conditions: ethanol molar ratio 0.5:1, seed crystal content 0.2%, specific mass: ethanol: 7.7459 g, n-octanoic acid: 11.6249 g, seed crystal: 0.1235 g, ultrasonic power 70 W, temperature 15 °C, ultrasonic times were 20, 40, 60 s respectively, and the standing time was 30 min. The cooling water circulation pump was turned on, and the ultrasonic probe with a tip diameter of 0.5 cm was immersed in the solution from the three-necked flask. The probe was located in the center of the solution, and the solution was ultrasonically treated and mixed. During the ultrasonic process, no additional stirring equipment was required. Considering factors such as equipment safety, high energy, and heat dissipation, the cooling water circulation pump was used to keep the temperature in the water bath at 15 °C, and the system temperature in the sucralose crystallization solution was monitored by a thermometer. Intermittent ultrasonic antisolvent crystallization was carried out at a frequency of 22.6 kHz and a power of 70 W. The suspension sample was extracted, and the solid-liquid two phases were centrifuged and separated. The lower-layer solid was dried at 50 °C and -0.1 MPa, and the sucralose product was characterized and the morphology of the sucralose product was observed by field emission scanning electron microscope (SEM), and the particle size distribution and aspect ratio were calculated.

[0022] Figure 1 It is the SEM diagram and particle size distribution diagram of the sucralose product in the intermittent ultrasonic-assisted antisolvent process. The sucralose product with an average size of 42.722 μm and an aspect ratio of 1.244 can be obtained.

[0023] Figure 2 It is the XRD diagram of the sucralose product. No new crystal phase appears in the sucralose product, but there are certain differences in the diffraction intensities of some parts.

[0024] Figure 3 It is the FT-IR diagram of the sucralose product. There is no obvious difference in the vibration spectra between the sucralose product and the commercial sucralose, which confirms that no new interaction forces are generated during the intermittent ultrasonic-assisted antisolvent process.

[0025] Figure 4 It is of the intermittent ultrasonic-assisted antisolvent crystallization and the commercial sucralose crystallization products 1The 1H-NMR spectra show that the chemical shifts of the sucralose product and commercial sucralose are consistent without any deviation. The purity of the sucralose product obtained by intermittent ultrasonic-assisted antisolvent crystallization remains unchanged, and no new impurities are generated.

[0026] Figure 5 These are the HPLC-ELSD spectra of the products obtained by intermittent ultrasonic-assisted antisolvent crystallization and commercial sucralose crystallization. The purity of the sucralose product and commercial sucralose remains unchanged, and no new impurities are generated.

[0027] The above are only the preferred embodiments of the present invention. All equivalent changes and modifications made according to the scope of the patent application of the present invention shall fall within the scope covered by the present invention.

Claims

1. A method for intermittent ultrasonic-assisted antisolvent crystallization of sucralose, characterized in that, It includes the following steps: at 15°C, dissolve sucralose solid in ethanol. After it is completely dissolved into a clear solution, add octanoic acid antisolvent and seed crystals, turn on the cooling water circulation pump and put the ultrasonic generator into the solution, and perform intermittent ultrasonic antisolvent crystallization on it at a frequency of 22.6 kHz and a power of 70 W; extract the suspension sample, centrifuge to separate the solid and liquid phases, and dry the lower-layer solid at 50°C and -0.1 MPa to obtain the sucralose product.

2. The method according to claim 1, wherein The seed crystal is sucralose with a purity of 98%; the molar ratio of octanoic acid antisolvent to ethanol is 0.5:1; the seed crystal content is 0.2%.

3. The method according to claim 1, wherein The octanoic acid antisolvent is n-octanoic acid solvent.

4. The method according to claim 1, characterized in that The operation method of the intermittent ultrasound is: stop the ultrasound at 20 s during nucleation, then let it stand for 30 min, continue the ultrasound for 40 s, then let it stand for 30 min, continue the ultrasound for 60 s, and then let it stand for 30 min.

5. A sucralose with a low length-to-diameter ratio and large crystal size, characterized in that, Prepared by using any one of the methods described in claims 1-4.

Images