L-tyrosine crystal as well as preparation method and application thereof

Abstract

The invention provides an L-tyrosine crystal as well as a preparation method and application thereof. The preparation method of the L-tyrosine crystal comprises the following steps: dissolving L-tyrosine in an acidic aqueous solution with the pH value of-1 to 2, and crystallizing at the temperature of 5-25 DEG C to obtain the L-tyrosine crystal. Compared with the L-tyrosine crystal in the prior art, the L-tyrosine crystal prepared by the method provided by the invention has higher bulk density (including bulk density and compactness), fluidity and purity, avoids the problems of large dust yield, poor fluidity and the like during application of the L-tyrosine crystal, reduces the space volume occupied by the product with the same mass, and improves the production efficiency. And the transportation cost is reduced.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical chemistry. Specifically, the present invention relates to an L-tyrosine crystal and a preparation method and application thereof. Background Art

[0002] As one of the essential amino acids for the human body, L-tyrosine has unique structural characteristics and is widely used in the fields of medicine, food, etc. At present, the main methods for preparing L-tyrosine include hydrolysis, synthesis, fermentation, and enzyme-catalyzed conversion. Among them, the enzyme-catalyzed conversion method uses phenol, pyruvic acid, and ammonia as raw materials, and utilizes tyrosine phenol lyase to carry out catalytic conversion reaction. Due to its strong specificity, high catalytic efficiency, mild reaction conditions, short reaction cycle, and easy separation of products, it has gradually become an important way to synthesize L-tyrosine. The L-tyrosine obtained by this method needs to be extracted by isoelectric point extraction. Generally, L-tyrosine is first dissolved by acid or alkali, and then the pH is adjusted to the isoelectric point by acid-base neutralization to crystallize, thereby obtaining L-tyrosine crystals.

[0003] Patent application CN114560783A discloses a method for extracting L-tyrosine. Specifically, after the crude L-tyrosine is obtained by the method, it is kept warm and dissolved with a dilute hydrochloric acid solution, and then activated carbon decolorization is performed, and then the activated carbon decolorization liquid is neutralized with an ammonia solution to a pH of 5.0-5.8, and the L-tyrosine fine product is collected by centrifugation. Patent application CN103343149A also uses the isoelectric point crystallization principle, uses hydrochloric acid to heat up and dissolve the crude product, and then performs activated carbon decolorization, and then the activated carbon decolorization liquid is neutralized with ammonia water to a pH of 4.0-5.0, and finally filtered, washed and dried. Patent application CN103224972A uses a similar acid-soluble alkali-analysis process, uses sodium hydroxide solution to heat up and dissolve, and after adding activated carbon decolorization, the solution is filtered, and the filtrate uses hydrochloric acid to adjust the pH value to 6, and the desired L-tyrosine is obtained after drying. The above patent applications all utilize the isoelectric point crystallization principle to separate, extract and purify crude L-tyrosine by acid dissolution and alkali precipitation or alkali dissolution and acid precipitation.

[0004] As L-tyrosine is increasingly used, the requirements for bulk density and crystals have been added to the indicators of L-tyrosine products. However, the L-tyrosine products currently extracted by isoelectric point method are mostly long needle-shaped or thin rod-shaped structures, and the crystals are fragile, with a bulk density of about 0.15-0.45. When used, they produce a lot of dust and have poor fluidity, which affects their application in additives and drugs.

[0005] Patent application CN106309379A discloses a method for preparing L-tyrosine granules. Specifically, the method adds water or ethanol to one or more of hydroxypropylmethylcellulose, ethylcellulose, methylcellulose, polyvinylpyrrolidone, cellulose acetate, maltodextrin, microcrystalline cellulose, mannitol, xylitol, sorbitol, glucose and nicotinamide to make a slurry; then L-tyrosine is placed in a granulator, the prepared slurry is added, and the mixture is stirred and mixed evenly to make L-tyrosine into small particles, and then dried in a fluidized bed at 75°C, and passed through a 40-mesh vibrating sieve to obtain L-tyrosine particles. The bulk density of the L-tyrosine particles prepared by this method is about 0.45, and additional chemical reagents are added, which affects the purity and usability of L-tyrosine.

[0006] In summary, the L-tyrosine crystals obtained by the current method have the disadvantages of being small and fragile, having low bulk density, poor fluidity and low purity. Summary of the invention

[0007] In view of the above problems, the purpose of the present invention is to provide an L-tyrosine crystal and a preparation method and use thereof. The inventors have found through research that, compared with the L-tyrosine crystals in the prior art, the L-tyrosine crystals of the present invention have higher bulk density (including bulk density and compactness), fluidity and purity, avoiding the problems of large dust generation and poor fluidity of the L-tyrosine crystals during application, while reducing the space volume occupied by products of equal quality and reducing transportation costs.

[0008] definition

[0009] The term "packing density" used in this article refers to the density of powder or granular material when it is piled up in a certain space, which reflects the compactness of the material in a certain space, including loose packing density (loose density) and tapped packing density (compactness).

[0010] The term "bulk density" used herein refers to the average density of a loose particle pile including pores inside and outside the particles and spaces between particles, which is obtained by dividing the total mass of the uncompacted particulate material in a naturally stacked state by the total volume of the pile.

[0011] The term "compactness" used in this article is also called tap density, which refers to the mass per unit volume of powder in a container after being tapped under specified conditions. Specifically, the tap density is obtained by putting a certain amount of powder into a container, vibrating it regularly under certain conditions, and compressing the gaps between the particles as much as possible, and finally reaching a level where the gaps between the particles cannot be reduced any further. When the volume of the powder in the container no longer decreases, the volume of the powder is read out, and then the weight of the powder is divided by the volume to obtain the tap density.

[0012] The term "Hausner ratio" used herein refers to apparent volume in loose state / tapped volume=compactness / bulk density. The Hausner ratio can reflect the fluidity of the powder. The smaller the Hausner ratio, the better the fluidity of the powder.

[0013] The above object of the present invention is achieved by providing the following technical solutions:

[0014] In a first aspect, the present invention provides a method for preparing L-tyrosine crystals, comprising: dissolving L-tyrosine in an acidic aqueous solution with a pH of -1 to 2, and then crystallizing at 5-25°C to obtain L-tyrosine crystals.

[0015] Preferably, the pH of the acidic aqueous solution is from -0.8 to 1.

[0016] Preferably, the crystallization is carried out at 10-20°C.

[0017] According to some embodiments of the present invention, the concentration of L-tyrosine in the acidic aqueous solution is 100-500 g / L, preferably 200-300 g / L.

[0018] According to some embodiments of the present invention, the acidic aqueous solution is selected from one or more of aqueous sulfuric acid, aqueous hydrochloric acid, aqueous phosphoric acid, aqueous acetic acid, aqueous nitric acid, aqueous perchloric acid and aqueous hydrobromic acid, preferably aqueous sulfuric acid.

[0019] According to some embodiments of the present invention, the dissolving is carried out at 50-80°C, preferably at 60-70°C.

[0020] According to some embodiments of the present invention, the crystallization is carried out under static or stirring conditions, preferably under stirring conditions; preferably, the stirring rate is 20-100 rpm, preferably 40-60 rpm.

[0021] According to some embodiments of the present invention, the crystallization is performed for 8-36 hours, preferably 10-24 hours.

[0022] According to some embodiments of the present invention, the method further comprises: performing solid-liquid separation on the crystal system obtained after crystallization, and sequentially washing and drying the solid after solid-liquid separation to obtain L-tyrosine crystals.

[0023] Preferably, the washing comprises: washing the separated solid with pure water until it becomes neutral.

[0024] Preferably, the weight ratio of the separated solid to pure water is 1:2-8.

[0025] Preferably, the drying temperature is 50-70°C, preferably 55-65°C.

[0026] Preferably, the drying time is 8-16 hours, preferably 10-14 hours.

[0027] According to some embodiments of the present invention, the method further comprises: using the liquid after solid-liquid separation as an acidic aqueous solution again for dissolving L-tyrosine and crystallizing steps.

[0028] Preferably, the concentration of L-tyrosine in the liquid obtained by dissolving L-tyrosine in the liquid after solid-liquid separation is 100-500 g / L, preferably 200-300 g / L.

[0029] According to some embodiments of the present invention, the method further comprises: adding activated carbon for decolorization after dissolving L-tyrosine in the acidic aqueous solution and before crystallization, and then removing the activated carbon by filtration.

[0030] Preferably, the weight ratio of L-tyrosine to activated carbon is 1:0.02-0.1.

[0031] Preferably, the decolorization temperature is 50-80°C, preferably 65-75°C.

[0032] Preferably, the decolorization time is 10-30 min, preferably 10-20 min.

[0033] According to some embodiments of the present invention, the method further comprises: sieving the obtained L-tyrosine crystals using a 40-80 mesh vibrating screen to obtain L-tyrosine particles.

[0034] In a second aspect, the present invention provides an L-tyrosine crystal, which is prepared by the preparation method according to the first aspect of the present invention.

[0035] According to some embodiments of the present invention, the packing density of the L-tyrosine crystals is 0.5-1 g / mL, preferably 0.6-0.8 g / mL.

[0036] According to some embodiments of the present invention, the bulk density of the L-tyrosine crystals is 0.5-0.7 g / mL, preferably 0.6-0.7 g / mL.

[0037] According to some embodiments of the present invention, the compactness of the L-tyrosine crystals is 0.7-1 g / mL, preferably 0.7-0.8 g / mL.

[0038] According to some embodiments of the present invention, the Hausner ratio of the L-tyrosine crystals is 1.10-1.34, preferably 1.19-1.30, and more preferably 1.19-1.26.

[0039] According to some embodiments of the present invention, the purity of the L-tyrosine crystals is greater than 99%.

[0040] According to some embodiments of the present invention, the L-tyrosine crystals have a columnar crystal structure.

[0041] In a third aspect, the present invention provides a bulk drug, which comprises L-tyrosine crystals prepared according to the preparation method described in the first aspect of the present invention or L-tyrosine crystals described in the second aspect of the present invention.

[0042] Preferably, the content of the L-tyrosine crystals in the bulk drug is greater than 99%.

[0043] In a fourth aspect, the present invention provides a pharmaceutical composition comprising L-tyrosine crystals prepared according to the preparation method described in the first aspect of the present invention or L-tyrosine crystals described in the second aspect of the present invention, and one or more pharmaceutically acceptable carriers.

[0044] In a fifth aspect, the present invention provides use of L-tyrosine crystals prepared according to the preparation method described in the first aspect of the present invention or L-tyrosine crystals described in the second aspect of the present invention in the preparation of food additives, nutritional supplements, cosmetics and / or drugs for treating phenylketonuria.

[0045] The present invention has at least the following beneficial effects:

[0046] 1. The present invention directly cools and crystallizes L-tyrosine after dissolving it under strong acidic conditions, without adjusting the pH to the isoelectric point of L-tyrosine (about 5.66) by acid-base neutralization. This not only simplifies the operation steps, but also can produce L-tyrosine crystals with a columnar crystal structure.

[0047] 2. Compared with the L-tyrosine crystals in the prior art, the L-tyrosine crystals prepared by the present invention have higher bulk density (including bulk density and compactness), better fluidity and higher purity. These improvements significantly reduce the dust generation of the L-tyrosine crystals during actual application, thereby solving the dust problem faced by traditional L-tyrosine crystals during use, while reducing the space volume occupied by products of equal quality and reducing transportation costs.

[0048] 3. The preparation method of the present invention is simple to operate and easy to industrialize.

[0049] 4. The preparation method of the present invention has universal applicability and can be used for the crystal preparation of commercially available L-tyrosine or L-tyrosine obtained by other methods. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] The specific embodiments of the present invention are described in conjunction with the following drawings, in which:

[0051] Figure 1 It is a microscope picture of the L-tyrosine crystals prepared in Example 1.

[0052] Figure 2 It is a microscope picture of the L-tyrosine crystals prepared in Comparative Example 1.

[0053] Figure 3 It is a microscope picture of L-tyrosine crystals prepared in Comparative Example 2.

[0054] Figure 4 is the X-ray powder diffraction pattern of the L-tyrosine crystals prepared in Example 1. DETAILED DESCRIPTION

[0055] The present invention is further described in detail below in conjunction with specific embodiments. The given examples are only for illustrating the present invention, but not for limiting the scope of the present invention.

[0056] The experimental methods used in the following examples and comparative examples are conventional methods unless otherwise specified. The reagents used in the following examples and comparative examples are commercially available products unless otherwise specified. Among them, the L-tyrosine raw material is prepared by the method of Example 4 in reference patent application CN117106813A. Comparative Examples 1 and 2 are carried out by reference to the isoelectric point crystallization process in patent application CN114560783A.

[0057] The bulk density and compactness are determined according to the 0993 bulk density and tap density determination method in the 2020 edition of the "Pharmacopoeia of the People's Republic of China".

[0058] The specific relationship between Hausner ratio and powder flowability is shown in the following table.

[0059] Table 1 Relationship between Hausner ratio and powder fluidity

[0060]

[0061]

[0062] The L-tyrosine purity test method is as follows:

[0063] Instruments and tools: High performance liquid chromatograph, one-hundred-thousandth balance, ultrasonic cleaner, volumetric flask, pipette.

[0064] Test solution: acetonitrile (chromatographic grade), 1 mol / L sodium hydroxide solution.

[0065] Chromatographic conditions: octadecylsilane bonded silica gel as filler; acetonitrile-water (volume ratio 10:90) as mobile phase; detection wavelength at 210 nm; column temperature at 40°C.

[0066] Preparation of reference solution: accurately weigh 10 mg of L-tyrosine reference substance, place it in a 10 ml volumetric flask, first add 1 ml of 1 mol / L sodium hydroxide solution to dissolve, then dilute to scale with water, mix well; accurately measure 1 ml, 2 ml, and 3 ml of the above solution into a 20 ml volumetric flask, dilute to scale with water, and make solutions containing about 0.05 mg, 0.1 mg, and 0.15 mg of L-tyrosine per 1 ml as reference solution. The injection concentration of the reference solution is 0.05-0.2 mg / ml.

[0067] Preparation of test solution: accurately measure 10 mg of L-tyrosine sample, place it in a 10 ml volumetric flask, first add 1 ml 1 mol / L sodium hydroxide solution to dissolve, then dilute to scale with water, shake well; accurately measure 1 ml of the above solution, place it in a 10 ml volumetric flask, add water to dilute to scale, as the test solution. The injection concentration of the test solution is about 0.1 mg / ml.

[0068] Take 20 μl of the above reference solution and test solution, inject them into the high performance liquid chromatograph, record the chromatogram, and the running time is 10 min.

[0069] Calculation of results: Use the injection concentration of the reference substance as the horizontal axis and the peak area as the vertical axis to draw a standard curve, and obtain the equation Y=aX+b, requiring linearity R2≥b. L-tyrosine content is calculated according to the following formula: L-tyrosine content (mg / mg)=(Ab) / ab; where A-peak area of ​​the sample; N-dilution multiple of the sample.

[0070] Example 1

[0071] (1) Prepare 850 mL of a sulfuric acid aqueous solution with a pH of -0.45, add it to a four-necked bottle, heat it to 65° C., then add 210 g of L-tyrosine, and stir at this temperature until it is completely dissolved;

[0072] (2) adding 5 g of activated carbon, stirring and decolorizing at 65° C. for 20 min, and then filtering with suction, filtering the filtrate through a 0.22 μm microporous filter membrane, and then stirring the filtrate at 15° C. and 50 rpm for crystallization for 24 h to obtain a solution containing L-tyrosine crystals;

[0073] (3) The solution containing L-tyrosine crystals was filtered to obtain a solid wet product and 800 mL of mother liquor, respectively. The solid wet product was rinsed three times with 400 mL of pure water and then dried at 60° C. for 12 h to obtain 86.5 g of L-tyrosine finished product with a yield of 41.2%, a purity of 99.8%, a bulk density of 0.6333 g / mL, a compactness of 0.7596 g / mL, a Hausner ratio of 1.199, and good fluidity.

[0074] Figure 1 The microscopic images of the L-tyrosine product obtained in this embodiment are shown, wherein (a) and (b) are microscopic images of the L-tyrosine product at 4*10 times magnification, and (c) and (d) are microscopic images of the L-tyrosine product at 10*10 times magnification. As can be seen from the figure, the L-tyrosine product presents a columnar crystal morphology, which is relatively regular and evenly distributed. The X-ray powder diffraction pattern of the L-tyrosine crystals obtained in this embodiment is as follows: Figure 4 shown.

[0075] Example 2

[0076] (1) Add the mother liquor collected in Example 1 into a four-necked bottle, heat it to 65° C., add 80 g of L-tyrosine, and stir at this temperature until it is completely dissolved;

[0077] (2) adding 5 g of activated carbon, stirring and decolorizing at 65° C. for 20 min, and then filtering with suction, filtering the filtrate through a 0.22 μm microporous filter membrane, and then stirring the filtrate at 15° C. and 50 rpm for crystallization for 24 h to obtain a solution containing L-tyrosine crystals;

[0078] (3) The solution containing L-tyrosine crystals was filtered to obtain a solid wet product and 750 mL of mother liquor, respectively. The solid wet product was rinsed three times with 400 mL of pure water and then dried at 60° C. for 12 h to obtain 75.8 g of L-tyrosine product with a yield of 94.8%, a purity of 99.8%, a bulk density of 0.6154 g / mL, a compactness of 0.7358 g / mL, a Hausner ratio of 1.1956, and good fluidity.

[0079] Microscopic observation showed that the L-tyrosine product prepared in this embodiment had a columnar crystal morphology, which was relatively regular and evenly distributed.

[0080] Example 3-6 Investigation of crystallization temperature

[0081] According to the method of Example 1, L-tyrosine finished product was prepared at the crystallization temperature shown in the following table. The XRD spectrum of the prepared L-tyrosine finished product was studied and compared with the XRD spectrum of the L-tyrosine crystal prepared in Example 1, and it was determined to be consistent with the crystal obtained in Example 1.

[0082] Table 2 Investigation of crystallization temperature

[0083]

[0084]

[0085] It can be seen from the above table that when the crystallization temperature is 5-25°C, the method of the present invention can obtain L-tyrosine crystals with high bulk density, high compactness, high fluidity and high purity; when the crystallization temperature is further preferably 10-20°C, the fluidity of the L-tyrosine crystals obtained by the method of the present invention is further improved.

[0086] Example 7-10 Investigation of pH of acidic aqueous solution

[0087] Table 3 Investigation of pH of acidic aqueous solution

[0088]

[0089] It can be seen from the above table that when the pH of the aqueous sulfuric acid solution is -1 to 2, the method of the present invention can obtain L-tyrosine crystals with high bulk density, high compactness, high fluidity and high purity; when the pH of the aqueous sulfuric acid solution is further preferably -0.8 to 1, the fluidity of the L-tyrosine crystals obtained by the method of the present invention is further improved.

[0090] Comparative Example 1

[0091] (1) Prepare 850 mL of a pH 0 hydrochloric acid aqueous solution (pH 0), add it to a four-necked bottle, heat it to 65° C., then add 210 g of L-tyrosine, and stir at this temperature until it is completely dissolved;

[0092] (2) Add 5 g of activated carbon, stir and decolorize at 65°C for 20 min, then filter with suction, filter the filtrate through a 0.22 μm microporous filter membrane, and collect the filtrate;

[0093] (3) preparing a 3M ammonia solution, slowly adding it to the filtrate at 50° C. until the pH is 5-6, and performing crystallization. The entire crystallization process is maintained for about 8 hours. When white turbidity appears, stop adding ammonia solution. After growing the crystals for 0.5 hours, continue to slowly add ammonia solution to the end point (pH is 5.66). The rotation speed is maintained at 50 rpm during the entire crystallization process to obtain a solution containing L-tyrosine crystals.

[0094] (4) The solution containing L-tyrosine crystals was filtered to obtain a solid wet product, which was then rinsed three times with 400 mL of pure water and then dried at 60° C. for 12 h to obtain 197.3 g of L-tyrosine product with a yield of 93.95%, a purity of 99.4%, a bulk density of 0.2157 g / mL, a compactness of 0.4485 gm / L, a Hausner ratio of 2.079, poor fluidity, and easy dusting during use.

[0095] Figure 2The microscopic image of the L-tyrosine product obtained in this comparative example at a magnification of 10*10 times is shown. As can be seen from the figure, the L-tyrosine product is in powder form, showing a broken small needle-shaped crystal morphology.

[0096] Comparative Example 2

[0097] (1) Prepare 850 mL of a sulfuric acid aqueous solution with a pH of -0.45, add it to a four-necked bottle, heat it to 65° C., then add 210 g of L-tyrosine, and stir at this temperature until it is completely dissolved;

[0098] (2) Add 5 g of activated carbon, stir and decolorize at 65°C for 20 min, then filter with suction, filter the filtrate through a 0.22 μm microporous filter membrane, and collect the filtrate;

[0099] (3) preparing a 1.5 M sodium hydroxide solution, slowly adding it to the filtrate at 50° C. until the pH is 5-6, and performing crystallization. The entire crystallization process is maintained for about 20 hours. When white turbidity appears, stop adding the sodium hydroxide solution. After growing the crystals for 0.5 hours, continue to slowly add the sodium hydroxide solution to the end point (pH is 5.66). The rotation speed is maintained at 50 rpm during the entire crystallization process to obtain a solution containing L-tyrosine crystals.

[0100] (4) The solution containing L-tyrosine crystals was filtered while hot to obtain a solid wet product, which was then rinsed three times with 400 mL of pure water and then dried at 60° C. for 12 h to obtain 198.1 g of L-tyrosine product with a yield of 94.33%, a purity of 99.6%, a bulk density of 0.3105 g / mL, a compactness of 0.6046 g / mL, a Hausner ratio of 1.947, poor fluidity, and easy dusting during use.

[0101] Figure 3 The microscopic image of the L-tyrosine product obtained in this comparative example at a magnification of 10*10 times is shown. As can be seen from the figure, the L-tyrosine product presents a thin rod-like crystal morphology.

[0102] The above are only several exemplary embodiments of the present invention, and are not intended to limit the present invention in any form. Although the present invention is disclosed as above with preferred embodiments, they are not intended to limit the present invention. Any technician familiar with the profession, without departing from the scope of the technical solution of the present invention, can make some changes or modifications to obtain equivalent or equivalent embodiments using the above disclosed technical content, all of which belong to the scope of the present invention.

Claims

1. A method for preparing L-tyrosine crystals, comprising: L-tyrosine is dissolved in an acidic aqueous solution with a pH of -1 to 2, and then crystallized at 5-25°C to obtain L-tyrosine crystals.

2. The preparation method according to claim 1, wherein The pH of the acidic aqueous solution is -0.8 to 1; Preferably, the crystallization is carried out at 10-20°C.

3. The preparation method according to claim 1 or 2, wherein The concentration of L-tyrosine in the acidic aqueous solution is 100-500 g / L, preferably 200-300 g / L; Preferably, the acidic aqueous solution is selected from one or more of an aqueous sulfuric acid solution, an aqueous hydrochloric acid solution, an aqueous phosphoric acid solution, an aqueous acetic acid solution, an aqueous nitric acid solution, an aqueous perchloric acid solution and an aqueous hydrobromic acid solution, preferably an aqueous sulfuric acid solution; Preferably, the dissolving is carried out at 50-80°C, preferably at 60-70°C; Preferably, the crystallization is carried out under static or stirring conditions, preferably under stirring conditions; further preferably, the stirring rate is 20-100 rpm, preferably 40-60 rpm; Preferably, the crystallization is carried out for 8-36 hours, preferably 10-24 hours.

4. The preparation method according to any one of claims 1 to 3, wherein The method further comprises: performing solid-liquid separation on the crystal system obtained after crystallization, and sequentially washing and drying the solid after solid-liquid separation to obtain L-tyrosine crystals; Preferably, the washing comprises: washing the separated solids with pure water until they are neutral; Preferably, the drying temperature is 50-70°C, preferably 55-65°C; Preferably, the drying time is 8-16 hours, preferably 10-14 hours; Preferably, the method further comprises: using the liquid after solid-liquid separation as an acidic aqueous solution again for dissolving L-tyrosine and crystallizing steps.

5. The preparation method according to any one of claims 1 to 4, wherein The method further comprises: adding activated carbon to decolorize the L-tyrosine after dissolving it in an acidic aqueous solution and before crystallizing it, and then removing the activated carbon by filtering; Preferably, the weight ratio of L-tyrosine to activated carbon is 1:0.02-0.1; Preferably, the decolorization temperature is 50-80°C, preferably 65-75°C; Preferably, the decolorization time is 10-30 min, preferably 10-20 min.

6. An L-tyrosine crystal, which is prepared by the preparation method according to any one of claims 1 to 5; Preferably, the bulk density of the L-tyrosine crystals is 0.5-1 g / mL, preferably 0.6-0.8 g / mL.

7. The L-tyrosine crystal according to claim 6, wherein The bulk density of the L-tyrosine crystals is 0.5-0.7 g / mL, preferably 0.6-0.7 g / mL; Preferably, the compactness of the L-tyrosine crystals is 0.7-1 g / mL, preferably 0.7-0.8 g / mL; Preferably, the Hausner ratio of the L-tyrosine crystals is 1.10-1.34, preferably 1.19-1.30, and more preferably 1.19-1.26; Preferably, the purity of the L-tyrosine crystals is greater than 99%; Preferably, the L-tyrosine crystals have a columnar crystal structure.

8. A bulk drug, comprising L-tyrosine crystals obtained by the preparation method according to any one of claims 1 to 5 or L-tyrosine crystals according to claim 6 or 7; Preferably, the content of the L-tyrosine crystals in the bulk drug is greater than 99%.

9. A pharmaceutical composition comprising the L-tyrosine crystals obtained by the preparation method according to any one of claims 1 to 5 or the L-tyrosine crystals according to claim 6 or 7, and one or more pharmaceutically acceptable carriers.

10. Use of the L-tyrosine crystals obtained by the preparation method according to any one of claims 1 to 5 or the L-tyrosine crystals according to claim 6 or 7 in the preparation of food additives, nutritional supplements, cosmetics and / or drugs for treating phenylketonuria.

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