L-alanine crystal and method for producing the same

Abstract

The application discloses L-alanine crystals and a preparation method thereof, relates to the technical field of L-alanine crystal preparation, and is characterized in that a morphology regulator is added into an aqueous solution containing L-alanine, crystallization is performed, and L-alanine crystals are obtained; the morphology regulator comprises any one or a combination of more than one of paclitaxel, isosorbide mononitrate and lactic acid. In the application, the morphology regulator is added into the aqueous solution containing L-alanine, the growth of the long axis of the crystals is inhibited, the growth of the short axis is promoted, and short rod-shaped L-alanine crystals are obtained. The application has the advantages of simple process, easy control and environmental protection.

Description

Technical Field

[0001] The present invention relates to the technical field of L-alanine preparation, and in particular to an L-alanine crystal with a rod-like morphology and a preparation method thereof. Background Art

[0002] Alanine (L-alanine), chemically known as 2-aminopropionic acid, has a molecular formula of C₃HₐNO₂ and occurs as colorless rhombic crystals or crystalline powder. It is soluble in water and ethanol, but insoluble in ether and acetone. L-alanine is a versatile nutrient that supports healthy muscle growth, increases energy, protects the nervous system, and improves immune system function. It also serves as a flavor enhancer, adding flavor to condiments and as a sourness corrector, improving the tartness of organic acids.

[0003] With the continued development of society and the economy, L-alanine is increasingly gaining market share in the pharmaceutical and food sectors. Currently, fermentation is the most common method for producing L-alanine, which is low-cost, environmentally friendly, and holds great promise. L-alanine crystals are typically obtained from aqueous L-alanine solutions or fermentation broths by crystallization. Optimizing L-alanine crystal morphology to improve L-alanine powder properties, such as tap density and flowability, and thus enhance product value is of great research interest. However, no relevant reports have yet been published. Summary of the Invention

[0004] Based on the technical problems existing in the background technology, the present invention proposes an L-alanine crystal with a rod-like morphology and a preparation method thereof. By adding a morphology modifier to the solution, short rod-shaped L-alanine is crystallized. The obtained product has good fluidity and high tap density. The process is simple and easy to control, and is convenient for transportation and storage.

[0005] The present invention provides a method for preparing L-alanine crystals, which comprises adding a morphology modifier to an aqueous solution containing L-alanine, and crystallizing to obtain L-alanine crystals.

[0006] The morphology regulator includes any one of paclitaxel, isosorbide mononitrate, and lactic acid, or a combination thereof.

[0007] Preferably, the amount of the morphology regulator added is 0.5-1.5% of the mass of L-alanine in the solution.

[0008] Preferably, the L-alanine crystals are rod-shaped crystals with an angle of repose of 30.9-35.5°.

[0009] Preferably, the crystallization is cooling crystallization or evaporation crystallization.

[0010] Furthermore, the cooling rate of the cooling crystallization is 0.1 to 0.5°C / min, preferably 0.2 to 0.4°C / min.

[0011] In the present invention, the initial temperature and the end temperature of the cooling crystallization are not clearly defined and can be set according to actual production; in this application, the initial temperature is designed to be 50-60°C and the end temperature is designed to be 10-20°C.

[0012] Preferably, the aqueous solution containing L-alanine is an L-alanine solution obtained by dissolving L-alanine in water, or an L-alanine fermentation broth or an L-alanine enzyme conversion liquid; preferably, the L-alanine fermentation broth or the L-alanine enzyme conversion liquid is a pretreated L-alanine fermentation broth or the L-alanine enzyme conversion liquid.

[0013] The L-alanine fermentation broth or L-alanine conversion liquid is subjected to pretreatment such as membrane filtration to remove impurities in the system, so that the L-alanine fermentation broth or L-alanine enzyme conversion liquid is in a clear state.

[0014] Preferably, a morphology modifier is added to a saturated aqueous solution containing L-alanine, stirred, and crystallized to obtain L-alanine crystals.

[0015] In the present invention, after the morphology regulator is added, the solution may be kept warm at 50-60° C. for 30-60 minutes to allow the morphology regulator to be fully dispersed in the solution.

[0016] In the present invention, when preparing a saturated aqueous solution containing L-alanine, the temperature is first raised to a temperature higher than the saturation temperature corresponding to the solubility of the saturated solution, which may be 5°C or higher, and stirred. The temperature is then lowered to the saturation temperature, so that the L-alanine in the solution is fully dissolved and saturated, and the solution is clear without crystal precipitation. The temperature of the saturated L-alanine solution is controlled and maintained for a period of time to keep the solution stable.

[0017] In the present invention, a morphology regulator may also be added to the clear unsaturated solution containing L-alanine. In this case, there is no need to increase the temperature or perform other operations to ensure that the L-alanine is fully dissolved.

[0018] Preferably, the method further comprises separating and drying the L-alanine crystals obtained by crystallization.

[0019] In the present invention, L-alanine can be separated by conventional separation and filtration devices without any specific requirements; for example, centrifugal separation can be used with a separation rate of 2500 to 3500 r / min.

[0020] In the present invention, L-alanine can be dried by conventional drying equipment without any specific requirements; for example, a forced air drying oven can be used for drying at 40-50° C. under normal pressure for 8-12 hours.

[0021] The application also provides the L-alanine crystal prepared by the method.

[0022] Preferably, the L-alanine crystal is a rod-shaped crystal, the crystal particle size is 150-1200 µm, the D50-D90 particle size is 500-1000 µm, and the tap density is 0.6-0.75 g / cm 3 The angle of repose is 30.9-35.5°.

[0023] Compared with the prior art, the application has the beneficial effects that: by adding a morphology regulator to the L-alanine-containing aqueous solution, the morphology regulator is adsorbed on the crystal surface of L-alanine during crystallization, on the one hand, the growth of the long axis of the crystal is inhibited, and on the other hand, the surface roughness of the short axis is increased, the growth of the short axis is promoted, and a short rod-shaped L-alanine crystal is obtained. The process of the application is simple and easy to control, and is green and environmentally friendly. BRIEF DESCRIPTION OF DRAWINGS

[0024] Figure 1 The SEM image of the L-alanine product obtained in Example 1 of the application;

[0025] Figure 2 The particle size distribution curve of the L-alanine product obtained in Example 1 of the application;

[0026] Figure 3 The SEM image of the L-alanine product obtained in Example 2 of the application;

[0027] Figure 4 The particle size distribution curve of the L-alanine product obtained in Example 2 of the application;

[0028] Figure 5 The SEM image of the L-alanine product obtained in Comparative Example 1 of the application. EMBODIMENT

[0029] The term “angle of repose” in the present application refers to the angle between the free surface of a powder pile formed by particulate matter (for example, crystalline alanine in the present application) in a gravitational field and the horizontal plane when the free surface is in a limit state of equilibrium. The smaller the angle of repose, the better the flowability of the powder. The method for determining the angle of repose used in the present application is the injection method.

[0030] The term “tap density” in the present application refers to the ratio of the mass of a powder formed by particulate matter (for example, crystalline alanine in the present application) to the volume of the container occupied by the powder (for example, the actual volume after tapping); the specific tap density can be determined by a powder tap density instrument.

[0031] In the following, the technical solutions of the present application are described in detail through specific examples. Example 1

[0032] A preparation method of L-alanine crystal, steps as follows:

[0033] (1) 50 mL of L-alanine saturated aqueous solution at 60 °C was prepared at 65 °C with stirring rate of 200 rpm, and after 30 min of incubation, the solution was cooled to 60 °C at a cooling rate of 0.5 °C / min to obtain L-alanine saturated solution at 60 °C;

[0034] (2) 1% of lactic acid by mass of L-alanine was added to the L-alanine saturated solution, and stirred and dispersed for 30 min;

[0035] (3) The solution in step (2) was cooled to crystallize at a cooling rate of 0.2 °C / min, and L-alanine was crystallized out, and the temperature was cooled to 20 °C for aggregation and growth;

[0036] (4) The solution in step (3) was centrifuged at a centrifugal speed of 3500 r / min, and the precipitate was dried at normal pressure at 50 °C for 12 h to obtain L-alanine rod-shaped crystal; the SEM image thereof is shown in Figure 1 , and the particle size distribution thereof is shown in Figure 2 . Example 2

[0037] (1) 50 mL of L-alanine saturated aqueous solution at 55 °C was prepared at 60 °C with stirring rate of 200 rpm, and after 40 min of incubation, the solution was cooled to 55 °C at a cooling rate of 0.3 °C / min to obtain L-alanine saturated solution at 55 °C;

[0038] (2) 1.5% of paclitaxel by mass of L-alanine was added to the L-alanine saturated solution, and stirred and dispersed for 60 min;

[0039] (3) The solution in step (2) was cooled to crystallize at a cooling rate of 0.5 °C / min, and L-alanine was crystallized out, and the temperature was cooled to 15 °C for aggregation and growth;

[0040] (4) The solution in step (3) was centrifuged at a centrifugal speed of 3000 r / min, and washed with water, and dried at normal pressure at 50 °C for 12 h to obtain L-alanine crystal; the SEM image thereof is shown in Figure 3 , and the particle size distribution thereof is shown in Figure 4 . Example 3

[0041] (1) 50 mL of L-alanine saturated aqueous solution at 55 °C was prepared at 60 °C with stirring rate of 200 rpm, and after 60 min of incubation, the solution was cooled to 55 °C at a cooling rate of 0.5 °C / min to obtain L-alanine saturated solution at 55 °C;

[0042] (2) Add 1.0% of isosorbide mononitrate to the L-alanine saturated solution by mass of L-alanine, and stir and disperse for 50 min;

[0043] (3) Cool the solution in step (2) to crystallize at a cooling rate of 0.3°C / min, and L-alanine is crystallized out and aggregated and grown at a temperature of 20°C;

[0044] (4) Centrifuge the solution in step (3) at a centrifugal speed of 3000 r / min, wash with water, and dry at 50°C under normal pressure for 12 h to obtain L-alanine crystals. The microscopic photograph and particle size distribution of the obtained L-alanine crystal product are similar to those of Example 2. Example 4

[0045] Compared with Example 1, the only difference is that step (1) is different, and the specific operation is as follows: prepare 50 mL of L-alanine saturated aqueous solution at 60°C, and stir at a stirring rate of 200 rpm. After 30 min of incubation, the L-alanine saturated solution at 60°C is obtained.

[0046] After detection, the particle size range of the prepared L-alanine crystals is 200-1000 µm, the tap density is 0.68 g / cm 3 , and the angle of repose is 31.2°. Example 5

[0047] Compared with Example 1, the only difference is that step (3) is different, and the temperature is cooled to 30°C, and the specific operation is as follows: cool the solution in step (2) to crystallize at a cooling rate of 0.2°C / min, and L-alanine is crystallized out and aggregated and grown at a temperature of 30°C.

[0048] After detection, the particle size range of the prepared L-alanine crystals is 150-600 µm, the tap density is 0.42 g / cm 3 , and the angle of repose is 37.6°. Example 6

[0049] (1) Prepare 50 mL of L-alanine saturated aqueous solution at 55°C at 60°C, and stir at a stirring rate of 200 rpm. After 60 min of incubation, cool the solution to 55°C at a cooling rate of 0.5°C / min to obtain the L-alanine saturated solution at 55°C;

[0050] (2) Add 1.5% of lactic acid to the L-alanine saturated solution by mass of L-alanine, and stir and disperse for 50 min;

[0051] (3) Cool the solution in step (2) to crystallize at a cooling rate of 0.3°C / min, and L-alanine is crystallized out and aggregated and grown at a temperature of 20°C;

[0052] (4) The solution of step (3) was centrifuged at a speed of 3500 r / min, washed with water, and dried at 50° C. at normal pressure for 12 h to obtain L-alanine crystals; the micrograph and particle size distribution of the obtained L-alanine crystal product were similar to those in Example 1. Example 7

[0053] (1) Prepare 50 mL of a 55°C saturated aqueous solution of L-alanine at 60°C with a stirring rate of 200 rpm. After keeping the temperature for 60 min, cool the solution to 55°C at a cooling rate of 0.5°C / min to obtain a 55°C saturated L-alanine solution.

[0054] (2) Add 0.5% of the mass of L-alanine to the saturated L-alanine solution and stir for 50 minutes;

[0055] (3) The solution in step (2) was cooled and crystallized at a cooling rate of 0.5°C / min, L-alanine crystals were precipitated, and the temperature was lowered to 20°C, where aggregation and growth occurred;

[0056] (4) The solution of step (3) was centrifuged at a speed of 3500 r / min, washed with water, and dried at 50° C. at normal pressure for 12 h to obtain L-alanine crystals; the micrograph and particle size distribution of the obtained L-alanine crystal product were similar to those in Example 1.

[0057] Comparative Example 1

[0058] Compared with Example 1, the only difference is that step (2) is not included.

[0059] The particle size of the L-alanine crystals obtained was found to be in the range of 150-300µm, with a tap density of 0.38g / cm 3 , the angle of repose is 38.2˚; its SEM image is as follows Figure 5 shown.

[0060] Comparative Example 2

[0061] Compared with Example 1, the only difference is that step (3) is different, and the cooling crystallization is carried out at a cooling rate of 0.6°C / min. The specific operation is as follows: the solution in step (2) is cooled and crystallized at a cooling rate of 0.6°C / min, L-alanine crystals are precipitated, and the temperature is lowered to 20°C, and aggregated and grown;

[0062] The particle size of the L-alanine crystals obtained was found to be in the range of 150-600µm, with a tap density of 0.58g / cm 3 , the angle of repose is 35.9˚.

[0063] Test Example 1

[0064] The product morphology of the products obtained in the examples and comparative examples was detected using a Malvern-3000 particle size analyzer. The particle size distribution obtained in Example 1 is as follows: Figure 2 As shown, the particle size distributions of Examples 2 and 3 are similar, as shown in Figure 4 The test results are shown in the following table:

[0065]

[0066] As can be seen from the above table, compared with Comparative Example 1 in which no morphology modifier was added, the aspect ratios of the L-alanine products in Examples 1-3 were all reduced after the morphology modifier was added, and the L-alanine crystals obtained in Example 1 were short rod-shaped crystals with uniform particle size distribution.

[0067] Test Example 2

[0068] The angle of repose and tap density of the L-alanine products obtained in the examples and comparative examples were detected, wherein the measurement results in Examples 1-3 and Comparative Example 1 are shown below:

[0069]

[0070] As can be seen from the table, compared to Comparative Example 1, the angle of repose of the L-alanine crystals in Examples 1-3 is smaller. The smaller the angle of repose, the better the product fluidity. The tap density of Examples 1-3 is also increased. Specifically, the lower angle of repose in Example 1 is reduced by 19.1% compared to Comparative Example 1, and the tap density is increased by 97.4%.

[0071] The above description is only a preferred specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any technician familiar with the technical field, within the technical scope disclosed by the present invention, who makes equivalent replacements or changes based on the technical solution and inventive concept of the present invention, should be covered by the scope of protection of the present invention.

Claims

1. A method for preparing L-alanine crystals, characterized in that: adding a morphology modifier to an aqueous solution containing L-alanine to crystallize and obtain L-alanine crystals; The morphology regulator is selected from any one or a combination of paclitaxel, isosorbide mononitrate, and lactic acid; and the added amount of the morphology regulator is 0.5-1.5% of the mass of L-alanine in the solution.

2. The method according to claim 1, characterized in that The L-alanine crystals are rod-shaped crystals with an angle of repose of 30.9 to 35.5°.

3. The method according to claim 1, characterized in that The crystallization is cooling crystallization or evaporation crystallization.

4. The method according to claim 3, wherein: The cooling rate of the cooling crystallization is 0.1-0.5°C / min.

5. The method according to claim 1, wherein The aqueous solution containing L-alanine is an L-alanine solution obtained by dissolving L-alanine in water, an L-alanine fermentation liquid, or an L-alanine enzyme conversion liquid.

6. The method according to claim 5, characterized in that The L-alanine fermentation liquid or L-alanine enzyme conversion liquid is a pretreated L-alanine fermentation liquid or L-alanine enzyme conversion liquid.

7. The method according to claim 1, characterized in that A morphology regulator is added to a clear saturated aqueous solution containing L-alanine, stirred, and crystallized to obtain L-alanine crystals.

8. The method according to any one of claims 1 to 7, characterized in that The method also includes separating and drying the L-alanine crystals obtained by crystallization.

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