L-alanine crystal and preparation method thereof

Abstract

The invention discloses an L-alanine crystal and a preparation method thereof. In particular to a preparation method of an L-alanine crystal, which comprises the following steps: mixing L-alanine with a morphology regulator in water to obtain a clear solution, and crystallizing to obtain the L-alanine crystal, wherein the morphology regulator comprises any one of L-aspartic acid, L-proline and glutamine, or a combination of the L-aspartic acid, the L-proline and the glutamine; the addition amount of the morphology regulator is 0.1-10% of the mass of the L-alanine. The crystal has the advantages of high bulk density, high tap density, length-diameter ratio close to 1: 1, small repose angle, good fluidity and simple and easily-controlled process.

Description

Technical Field

[0001] This invention relates to an L-alanine crystal and its preparation method. Background Technology

[0002] L-Alanine is a basic building block of proteins and one of the more than 20 essential amino acids that make up human proteins. It has significant biological value and is an important raw material in chemical and pharmaceutical fields. L-Alanine's chemical name is 2-aminopropionic acid, with the molecular formula C3H7NO2. It appears as colorless orthorhombic crystals or crystalline powder. Due to its rod-shaped crystal morphology, it has low bulk density and poor flowability. Optimizing the crystal morphology of L-Alanine to improve its powder properties, such as bulk density, tap density, and flowability, is of great research significance for increasing product added value. However, current research on L-Alanine morphology optimization is limited. Only CN117586139A reports some additives that improve its morphology, but even after improvement, it still remains rod-shaped, merely reducing the aspect ratio of L-Alanine, which does not meet the physical property requirements. Summary of the Invention

[0003] The technical problem to be solved by the present invention is to overcome the defects of the existing L-alanine rod-shaped crystals, such as low bulk density, low tap density, poor fluidity, and complex and difficult-to-control process. The present invention provides an L-alanine crystal and its preparation method, which has high bulk density, high tap density, aspect ratio close to 1:1, small angle of repose, good fluidity, and simple and easy-to-control process.

[0004] The present invention solves the above-mentioned technical problems through the following technical solution:

[0005] This invention provides a method for preparing L-alanine crystals, which includes the following steps: mixing L-alanine with a morphology modifier in water to obtain a clear solution, and then crystallizing to obtain L-alanine crystals;

[0006] The morphology modifier includes any one or a combination of L-aspartic acid, L-proline, and glutamic dipeptide.

[0007] The amount of the morphology modifier added is 0.1-10% of the mass of L-alanine.

[0008] In some implementation schemes, the amount of water used and the mixing temperature are not limited, as long as a clear solution is obtained.

[0009] In this invention, the mass of the water is preferably 2.5-3.5 times, for example, 3 times, the mass of L-alanine. The mixing temperature is preferably 60-90°C, more preferably 70-80°C.

[0010] In some embodiments, the crystallization can be a conventional crystallization method in the art, preferably cooling crystallization or evaporation crystallization, or a combination of both, more preferably cooling crystallization.

[0011] In some embodiments, the crystallization process includes controlling the starting and ending temperatures. The starting temperature may be a conventional starting temperature, preferably 60-90°C, more preferably 70-80°C. The ending temperature may be a conventional ending temperature, preferably 0-30°C, for example 20-25°C.

[0012] In some embodiments, the time taken to reach the endpoint temperature from the starting temperature during the crystallization process can be selected according to actual needs. Preferably, it is 3-12 hours, more preferably 5-10 hours, for example 5, 7, or 10 hours.

[0013] In some embodiments, during the crystallization operation, the cooling rate from the starting temperature to the ending temperature can be 1-20°C / h, preferably 2-10°C / h, more preferably 2-5°C / h, for example 2.5, 3.57, or 5°C / h.

[0014] In some implementations, the crystallization operation is preferably any of the following operations:

[0015] (1) The initial temperature is 70~80℃, and the temperature is reduced to 25℃ within 5 hours;

[0016] (2) The initial temperature is 70~80℃, and the temperature is reduced to 25℃ within 10 hours;

[0017] (3) The initial temperature is 70~80℃, and the temperature is reduced to 25℃ within 7 hours.

[0018] The crystallization process of this invention includes filtration, washing, and drying. The filtration can be a conventional filtration method in the art, preferably pressure filtration or vacuum filtration. The solvent used for washing is a conventional washing solvent in the art, preferably ethanol or water. The drying is a conventional drying method in the art, preferably vacuum drying, and drying is considered complete when constant weight is reached.

[0019] In some implementations, the post-crystallization process is preferably vacuum filtration, washing with one volume of ethanol, and drying to constant weight.

[0020] The present invention also provides an L-alanine crystal, which is a crystal prepared by the above-described preparation method.

[0021] In some embodiments, the L-alanine crystals are preferably in bulk form.

[0022] In some embodiments, the bulk density of the L-alanine crystals is preferably 0.65~0.75 g / mL.

[0023] In some embodiments, the tap density of the L-alanine crystals is preferably 0.80~0.90 g / mL.

[0024] In some embodiments, the aspect ratio of the L-alanine crystal is preferably 1:1.05-1:1.08.

[0025] In some embodiments, the angle of repose of the L-alanine crystal is preferably 22-24°.

[0026] The present invention also provides an L-alanine crystal, which preferably has the following characteristics:

[0027] (1) It is a massive crystal

[0028] (1) The bulk density is 0.65~0.75 g / mL;

[0029] (2) The tap density is 0.80~0.90 g / mL;

[0030] (3) The aspect ratio is 1:1.05-1:1.08;

[0031] (4) The angle of repose is 22-24°.

[0032] Without violating common sense in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0033] The reagents and raw materials used in this invention are all commercially available.

[0034] The positive and progressive effects of this invention are as follows:

[0035] (1) The present invention prepares L-alanine bulk crystals by adding a specific morphology modifier to an aqueous solution of L-alanine.

[0036] (2) The bulk density and tap density of L-alanine block crystals prepared by the present invention are significantly improved, the aspect ratio is close to 1:1, the angle of repose is significantly reduced, and the fluidity is also significantly improved.

[0037] Terminology Explanation

[0038] In this invention, the term "length-to-diameter ratio" is the ratio of the longest diameter passing through the interior of the particle to the longest diameter perpendicular to it. Attached Figure Description

[0039] Figure 1 A polarized light microscope image of the L-alanine product of Example 1 of the present invention is shown.

[0040] Figure 2 A polarized light microscope image of the L-alanine product of Example 2 of the present invention is shown.

[0041] Figure 3 A polarized light microscope image of the L-alanine product of Example 3 of the present invention is shown.

[0042] Figure 4 A polarized light microscope image of the L-alanine product of Comparative Example 1 of the present invention is shown.

[0043] Figure 5 A polarized light microscope image of the L-alanine product of Comparative Example 2 of the present invention is shown.

[0044] Figure 6 A polarized light microscope image of the L-alanine product of Comparative Example 4 of the present invention is shown.

[0045] Figure 7 A polarized light microscope image of the L-alanine product of Comparative Example 5 of the present invention is shown. Detailed Implementation

[0046] The present invention will be further illustrated by way of embodiments below, but the present invention is not limited to the scope of the embodiments described herein.

[0047] Example 1:

[0048] 50 g of L-alanine solid was dissolved in 150 g of water (3 times the mass of L-alanine) at 70–80 °C. 1 g of L-aspartic acid (2% of the mass of L-alanine) was added, and the solution was stirred until dissolved. The solution was then cooled to 25 °C over 5 hours, filtered, washed with 50 mL of ethanol, and dried to constant weight. A microscopic photograph of the resulting solid is shown below. Figure 1 As shown. The bulk density of the product is 0.75 g / mL, and the tap density is 0.90 g / mL. The mass of the product obtained is 40 g, with a yield of 80%. The aspect ratio is 1:1.08. The angle of repose is 22°.

[0049] Example 2:

[0050] 50 g of L-alanine solid was dissolved in 150 g of water (3 times the mass of L-alanine) at 70–80 °C. 1.5 g of L-proline (3% of the mass of L-alanine) was added, and the solution was stirred until dissolved. The solution was then cooled to 25 °C over 10 hours, filtered, washed with 50 mL of cold water, and dried to constant weight. A microscopic photograph of the resulting solid is shown below. Figure 2 As shown. The bulk density of the product is 0.68 g / mL, and the tap density is 0.83 g / mL. The mass of the product obtained is 40 g, with a yield of 80%. The aspect ratio is 1:1.05. The angle of repose is 24°.

[0051] Example 3:

[0052] 50g of L-alanine solid was dissolved in 150g of water (3 times the mass of L-alanine) at 70-80℃. 5g of glutamyl dipeptide (10% of the mass of L-alanine) was added, and the solution was stirred until dissolved. The solution was then cooled to 25℃ over 7 hours, filtered, washed with 50mL of ethanol, and dried to constant weight. A microscopic image of the resulting solid is shown below. Figure 3 As shown. The bulk density of the product is 0.65 g / mL, and the tap density is 0.81 g / mL. The mass of the product obtained is 40 g, with a yield of 80%. The aspect ratio is 1:1.05. The angle of repose is 24°.

[0053] Comparative Example 1:

[0054] 50 g of L-alanine solid was dissolved in 150 g of water (three times the mass of L-alanine) at 70–80 °C with stirring until dissolved. The solution was then cooled to 25 °C over 5 hours, filtered, washed with 50 mL of ethanol, and dried. A microscopic image of the resulting solid is shown below. Figure 4 As shown. The bulk density of the product is 0.35 g / mL, and the tap density is 0.49 g / mL. The mass of the product obtained is 40 g, with a yield of 80%. The aspect ratio is 1:17. The angle of repose is 43°.

[0055] Comparative Example 2:

[0056] 50 g of L-alanine solid was dissolved in 150 g of water (3 times the mass of L-alanine) at 70–80 °C. 0.02 g of L-aspartic acid (0.04% of the mass of L-alanine) was added, and the solution was stirred until dissolved. The solution was then cooled to 25 °C over 5 hours, filtered, washed with 50 mL of ethanol, and dried to constant weight. A microscopic image of the resulting solid is shown below. Figure 5 As shown. The bulk density of the product is 0.55 g / mL, and the tap density is 0.67 g / mL. The mass of the product obtained is 40 g, with a yield of 80%. The aspect ratio is 1:3.2. The angle of repose is 36°.

[0057] Comparative Example 3:

[0058] 50 g of solid L-alanine was dissolved in 150 g of water (3 times the mass of L-alanine) at 70–80 °C. 7.5 g of L-aspartic acid (15% of the mass of L-alanine) was added, and the solution was stirred until dissolved. The solution was then cooled to 25 °C over 5 hours, filtered, washed with 50 mL of ethanol, and dried to constant weight. The bulk density of the product was 0.75 g / mL, and the tap density was 0.90 g / mL. The yield was 20 g, with a yield of 40%.

[0059] Comparative Example 4:

[0060] 50 g of L-alanine solid was dissolved in 150 g of water (3 times the mass of L-alanine) at 70–80 °C. 1.5 g of L-glutamic acid (3% of the mass of L-alanine) was added, and the solution was stirred until dissolved. The solution was then cooled to 25 °C over 10 h, filtered, washed with 50 mL of ethanol, and dried to constant weight. A microscopic image of the resulting solid is shown below. Figure 6 As shown. The bulk density of the product is 0.22 g / mL, and the tap density is 0.43 g / mL. The aspect ratio is 1:13. The angle of repose is 40°.

[0061] Comparative Example 5:

[0062] 50 g of L-alanine solid was dissolved in 150 g of water (3 times the mass of L-alanine) at 70–80 °C. 1.5 g of L-glutamine (3% of the mass of L-alanine) was added, and the solution was stirred until dissolved. The solution was then cooled to 25 °C over 10 h, filtered, washed with 50 mL of ethanol, and dried to constant weight. A microscopic image of the resulting solid is shown below. Figure 7 As shown. The bulk density of the product is 0.18 g / mL, and the tap density is 0.32 g / mL. The aspect ratio is 1:9. The angle of repose is 40°.

Claims

1. A method for preparing L-alanine crystals, characterized in that, It includes the following steps: In water, L-alanine is mixed with a morphology modifier to obtain a clear solution, which is then crystallized to obtain L-alanine crystals. The morphology modifier includes any one or a combination of L-aspartic acid, L-proline, and glutamic dipeptide. The amount of the morphology modifier added is 0.1-10% of the mass of L-alanine.

2. The method according to claim 1, characterized in that, The mass of the water is 2.5 to 3.5 times, for example, 3 times, the mass of L-alanine.

3. The method according to claim 1, characterized in that, The mixing temperature is 60-90℃, preferably 70-80℃.

4. The method according to claim 1, characterized in that, The crystallization is either cooling crystallization or evaporation crystallization, or a combination of both, with cooling crystallization being preferred.

5. The method according to claim 1, characterized in that, It satisfies one or more of the following conditions: (1) The crystallization process includes controlling the starting temperature and the ending temperature; (2) The initial temperature is 60-90℃, preferably 70-80℃; (3) The endpoint temperature is 0-30℃, for example 20-25℃; (4) In the crystallization operation, the time from the starting temperature to the ending temperature is 3-12 hours, preferably 5-10 hours, for example 5, 7 or 10 hours; (5) In the crystallization operation, the cooling rate from the starting temperature to the ending temperature is 1-20℃ / h, preferably 2-10℃ / h, more preferably 2-5℃ / h, for example 2.5, 3.57 or 5℃ / h.

6. The method according to claim 5, characterized in that, The crystallization operation is any of the following operations: (1) The initial temperature is 70~80℃, and the temperature is reduced to 25℃ within 5 hours; (2) The initial temperature is 70~80℃, and the temperature is reduced to 25℃ within 10 hours; (3) The initial temperature is 70~80℃, and the temperature is reduced to 25℃ within 7 hours.

7. The method according to claim 1, characterized in that, It satisfies one or more of the following conditions: (1) The operations after crystallization include filtration, washing and drying; (2) The filtration is gravity filtration or vacuum filtration.

8. The method according to claim 1, characterized in that, The L-alanine crystals satisfy one or more of the following conditions: (1) It is a massive crystal; (2) The bulk density is 0.65~0.75 g / mL; (3) The tap density is 0.80~0.90 g / mL; (4) The aspect ratio is 1:1.05-1:1.08; (5) The angle of repose is 22-24°.

9. An L-alanine crystal, prepared by the method according to any one of claims 1-8.

10. An L-alanine crystal that satisfies one or more of the following conditions: (1) It is a massive crystal; (2) The bulk density is 0.65~0.75 g / mL; (3) The tap density is 0.80~0.90 g / mL; (4) The aspect ratio is 1:1.05-1:1.08; (5) The angle of repose is 22-24°.

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