L-glutamic acid amlodipine as well as preparation method and application thereof

Abstract

The chemical structural formula of the L-glutamic acid amlodipine is as follows: # imgabs0 #, and the L-glutamic acid amlodipine is prepared by the following steps: dissolving amlodipine in an organic solvent and purified water, adding L-glutamic acid, carrying out heating reflux, naturally cooling to room temperature, introducing a refrigerant, carrying out heat preservation crystallization, carrying out suction filtration, and drying to obtain the L-glutamic acid amlodipine. Compared with the prior art, the L-glutamic acid amlodipine has the advantages that the stability is good, the L-glutamic acid amlodipine can be well applied to treatment of conditions of coronary spasm, hypertension, myocardial infarction and the like, the synthesis process is few, the L-glutamic acid amlodipine can be used for preparing L-glutamic acid amlodipine tablets, the dissolution rate of the tablets is good, the bioavailability is high, and the preparation process is simple. The bioavailability of the L-glutamic acid amlodipine is favorably improved.

Description

Technical Field

[0001] The present invention relates to the medical field, and in particular to L-glutamic acid amlodipine and a preparation method and application thereof. Background Art

[0002] Amlodipine, chemical name is 6-methyl-2-(2-aminoethoxy)methyl-4-(2-chlorophenyl)-1,4-dihydro-3,5-pyridinedicarboxylic acid methyl ethyl ester, molecular formula is C 20 H 25 ClN2O5, Amlodipine is a typical representative of the third generation of 1,4-dihydropyridine calcium antagonists. It is mainly used in the treatment of hypertension and angina pectoris in clinical practice. It was first successfully developed by Pfizer in the United States and first launched in the United States and Ireland in 1990. Compared with conventional calcium antagonists, amlodipine has the following three advantages: (1) slow onset and low incidence of side effects; (2) long plasma half-life (35-50h), patients only need to take the drug once a day, which can not only greatly improve patient compliance, but also ensure 24h effective blood drug concentration, thereby avoiding myocardial ischemia and infarction caused by early morning blood pressure fluctuations in hypertensive patients; (3) within the therapeutic dose range, it has a strong vasodilatory effect, but does not inhibit myocardial contractility and activate the neuro-hormonal system like conventional calcium antagonists. Therefore, in addition to being used to treat hypertension and angina pectoris, it is very promising for the treatment of heart failure, which is not available in general calcium antagonists.

[0003] Since amlodipine has poor water solubility and is easy to agglomerate, it does not meet the requirements of preparation production. Therefore, its marketed drug form is mainly a compound that forms salts with different acid radicals. At present, there are many reports on the formation of amlodipine salts. Chinese patent CN1850801A reports the formation of salts of benzenesulfonic acid and amlodipine; European patent EP89167 reports the formation of salts of maleic acid and amlodipine; Chinese patent CN112538044A reports the formation of salts of methanesulfonic acid and amlodipine; Chinese patent CN109651236A reports the preparation and application of aspartic acid and amlodipine salt crystals. Aspartic acid participates in a variety of biochemical reactions in the human body as a substrate or cofactor for certain enzymes. It also participates in energy metabolism. At normal doses, aspartic acid is generally considered to be relatively safe. However, excessive intake of aspartic acid may lead to overactivation of glutamate-aspartate synthetase, which in turn leads to increased nerve excitability and induces neurotoxic reactions. Summary of the invention

[0004] The purpose of the present invention is to provide an L-glutamate amlodipine and a preparation method and application thereof.

[0005] The purpose of the present invention can be achieved by the following technical solutions:

[0006] In one aspect, the present invention provides an L-glutamate amlodipine, whose chemical structural formula is as follows:

[0007]

[0008] In a second aspect, the present invention provides a method for preparing the above-mentioned L-glutamic acid amlodipine, comprising the following preparation steps: dissolving amlodipine in an organic solvent and purified water, adding L-glutamic acid, heating to reflux or heating and stirring, and then naturally cooling to room temperature, then introducing a refrigerant to keep warm for crystallization, suction filtering, and drying to obtain the L-glutamic acid amlodipine, and the reaction scheme is as follows:

[0009]

[0010] Preferably, the organic solvent is an alcohol solvent, and the alcohol solvent is selected from any one of methanol, ethanol, propanol or isopropanol.

[0011] Preferably, the weight ratio of amlodipine to alcohol solvent is 1:2-4.

[0012] Preferably, the weight ratio of amlodipine to purified water is 1:0.5-1.5.

[0013] Preferably, the molar ratio of amlodipine to L-glutamic acid is 1:0.9-1.5.

[0014] Preferably, the process of dissolving amlodipine in an organic solvent and purified water is as follows: under heating and stirring conditions, amlodipine is first added to an alcohol solvent, and then purified water is added until the amlodipine is completely dissolved.

[0015] Preferably, the heating reflux time is 1 h-18 h, and the heating temperature is determined according to the boiling point of the alcohol solvent.

[0016] Preferably, the refrigerant heat preservation and crystallization time is 2-10 hours.

[0017] Preferably, the refrigerant insulation crystallization temperature is -20 to 40°C.

[0018] Preferably, the refrigerant includes any one of hydrocarbons and freon.

[0019] The L-glutamate amlodipine prepared by the invention can be used to prepare a stable and highly effective drug combination for preventing or treating hypertension.

[0020] In a third aspect, the present invention further provides an L-glutamate amlodipine tablet, comprising the above-mentioned L-glutamate amlodipine.

[0021] Preferably, the L-glutamate amlodipine tablet comprises the following components in parts by weight: 5 to 12 parts of L-glutamate amlodipine, 30 to 60 parts of filler, 2 to 5 parts of disintegrant, 0.5 to 2.5 parts of lubricant, and 0.3 to 0.8 parts of silicon dioxide.

[0022] Preferably, the filler comprises microcrystalline cellulose and anhydrous calcium hydrogen phosphate.

[0023] Preferably, the disintegrant comprises one or more of low-substituted hydroxypropyl cellulose, cross-linked polyvinyl pyrrolidone, cross-linked sodium carboxymethyl cellulose, and sodium carboxymethyl starch.

[0024] Preferably, the lubricant includes one or more of sodium stearyl fumarate and magnesium stearate.

[0025] In a fourth aspect, the present invention further provides a method for preparing the L-glutamate amlodipine tablets, comprising the following steps: weighing each weight portion of L-glutamate amlodipine, a filler and a disintegrant, mixing them evenly, sieving, adding a lubricant and silicon dioxide, mixing them evenly, and directly tableting to obtain the L-glutamate amlodipine tablets.

[0026] Glutamate mainly acts as a neurotransmitter in the human central nervous system, transmitting nerve signals by binding to specific receptors. Glutamate receptors include ion channel receptors and metabolic coupling receptors. L-glutamate, as a non-essential amino acid for the human body, plays an important role in the medical field. It is one of the basic amino acids for nitrogen metabolism in biological organisms and is of great significance in metabolism. After being absorbed by the human body, glutamate easily forms glutamine with blood ammonia, which can eliminate the toxic effects in the metabolic process. Therefore, it can prevent and treat hepatic coma and protect the liver. It is an auxiliary drug for patients with liver diseases. At the same time, amlodipine, as a dihydropyridine calcium antagonist, can inhibit calcium ions from crossing the membrane into vascular smooth muscle and myocardium. The contraction process of myocardium and vascular smooth muscle depends on the extracellular calcium ions entering the cell through ion channels. It can selectively inhibit calcium ion transmembrane transport, and its effect on vascular smooth muscle cells is stronger than that on myocardial cells. In addition, amlodipine does not affect the concentration of serum calcium. Within the physiological pH range, amlodipine is an ionized complex that achieves its gradual effect by slowly binding / decomposing with calcium channel receptors at the binding site. Therefore, the present invention provides a feasible preparation process for combining L-glutamic acid and amlodipine to synthesize L-glutamic acid amlodipine.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] (1) The present invention introduces L-glutamic acid and successfully obtains the salt of L-glutamic acid and amlodipine.

[0029] (2) Compared with benzenesulfonic acid, maleic acid, methanesulfonic acid, etc., L-glutamic acid introduced in the present invention is one of the 20 common α-amino acids constituting proteins. It is a coded amino acid in protein synthesis and a non-essential amino acid for mammals. It can be converted from glucose in the body and occupies an important position in the body. It can be well used in combination with amlodipine for the treatment of coronary spasm, hypertension, myocardial infarction, etc.

[0030] (3) The L-glutamate amlodipine prepared by the present invention can be used to further prepare stable and highly effective L-glutamate amlodipine tablets for preventing or treating hypertension.

[0031] (4) The L-glutamate amlodipine prepared by the present invention has good stability, and the L-glutamate amlodipine tablet has good dissolution, which is beneficial to improving the bioavailability of L-glutamate amlodipine.

[0032] (5) The present invention has few synthesis steps, and only involves purified water and alcohol solvents in the preparation process, which is highly safe and has good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 The structural formula of L-glutamic acid amlodipine of the present invention is shown in FIG.

[0034] Figure 2 It is a preparation process flow chart of the preparation of L-glutamic acid amlodipine of the present invention;

[0035] Figure 3 is the nuclear magnetic spectrum of L-glutamate amlodipine in Example 1 of the present invention;

[0036] Figure 4 is the infrared spectrum of L-glutamate amlodipine in Example 1 of the present invention;

[0037] Figure 5 is the XRD powder diffraction pattern of the L-glutamate amlodipine crystal form in Example 1 of the present invention;

[0038] Figure 6 It is the high performance liquid chromatogram of L-glutamate amlodipine in Example 1 of the present invention. DETAILED DESCRIPTION

[0039] The present invention is described in detail below in conjunction with the accompanying drawings and specific embodiments. This embodiment is implemented based on the technical solution of the present invention, and provides a detailed implementation method and specific operation process, but the protection scope of the present invention is not limited to the following embodiments.

[0040] Unless otherwise specified, the reagents, methods, instruments and equipment used in the present invention are conventional reagents, methods, instruments and equipment in the art. Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0041] Example 1

[0042] The preparation process of the present invention is as follows Figure 2 As shown, amlodipine (20.0 g, 48.90 mmol) was added to anhydrous ethanol (45.0 g) solvent, heated and stirred, purified water (15.0 g) was added, the temperature was controlled to 77°C until all the materials were dissolved, L-glutamic acid (8.9 g, 60.20 mmol) was added, heated to reflux for 1 hour, cooled naturally to room temperature, and kept at 0-10°C for crystallization for 2 hours. After the crystallization was completed, the centrifugal filter was filtered until no liquid flowed out, and the obtained filter cake was dried to obtain 24.5 g of L-glutamic acid amlodipine, whose structural formula is as follows Figure 1 As shown, the molar yield is 90.07%.

[0043] The spectrum was tested using Qone AS400, DMSO-d6 was used as the test solvent, and the test frequency was 400HZ. The results are as follows: Figure 3 As shown, the IR spectrum (infrared spectrum) is as follows Figure 4 The XRD powder diffraction pattern of the crystal form is shown in Figure 5 In X-ray powder diffraction, the L-glutamic acid amlodipine prepared in Example 1 has peaks at diffraction angles 2θ of 10.22±0.2°, 13.72±0.2°, 18±0.2°, 20.04±0.2°, 20.56±0.2°, 21.46±0.2°, 22.08±0.2°, 23.14±0.2°, 23.8±0.2°, 24.26±0.2°, 25.66±0.2°, 26.12±0.2°, 27.66±0.2°, 28.82±0.2°, 30.02±0.2°, 31.06±0.2°, and 33.72±0.2°. The purity of the L-glutamic acid amlodipine prepared in Example 1 was tested by liquid chromatography detection area normalization method, and the results were shown in Table 1. Figure 6 The purity of the product is above 99%, which meets the needs of high-standard pharmaceutical production.

[0044] Peak table 1

[0045] PDA Ch1 237nm

[0046] Peak Retention time high area area% 1 3.748； 958； 9677； 0.036 2 4.302 1958； 17626； 0.065 3 4.548； 408； 3742； 0.014 4 4.789； 1358； 11739； 0.043 5 5.194； 2042； 16611； 0.061 6 7.030； 1216； 14639； 0.054 7 7.993； 426； 6077； 0.022 8 8.985； 132； 1372； 0.005 9 10.505； 413； 7382； 0.027 10 13.775； 635； 12866； 0.047 11 14.221； 691； 15623； 0.058 12 15.789； 1727； 41510； 0.153 13 28.183 472830； 26928468； 99.414 total 484794 27087332 100.000

[0047] Example 2

[0048] Amlodipine (500.0 g, 1.22 mmol) was added to a methanol (1000.0 g) solvent, heated and stirred, purified water (400.0 g) was added, the temperature was controlled to 65°C until all the materials were dissolved, L-glutamic acid (100.0 g, 0.68 mol) was added, heated to reflux for 2 hours, naturally cooled for crystallization, cooled to room temperature, and kept at -15°C for crystallization for 2 hours. After the crystallization was completed, centrifugation was performed until no liquid flowed out, and the obtained filter cake was dried to obtain 604.9 g of L-glutamic acid amlodipine, with a molar yield of 88.97%.

[0049] Example 3

[0050] Add amlodipine (2.0 Kg, 4.89 mmol) to methanol (4.5 Kg) solvent, heat and stir, add purified water (2.0 Kg), heat to 64°C, until all the materials are dissolved, add L-glutamic acid (0.9 Kg, 6.12 mmol), heat and reflux for 3 hours, cool to room temperature, and keep at 0°C-5°C for 2 hours for crystallization. After the crystallization is completed, centrifuge and filter until no liquid flows out, and the obtained filter cake is dried to obtain 2.48 Kg of L-glutamic acid amlodipine, with a molar yield of 91.18%.

[0051] Example 4

[0052] Add amlodipine (3.0Kg, 7.34mol) to anhydrous ethanol (6.3Kg) solvent, heat and stir, add purified water (0.8Kg), control the temperature to 78°C until all the materials are dissolved, add L-glutamic acid (1.1Kg, 7.34mol) in batches, heat and stir for 6 hours, cool to room temperature, and keep at 0°C-5°C for 3 hours for crystallization. After the crystallization is completed, filter by suction, rinse the filter cake twice with the filtrate, and dry the obtained filter cake to obtain 3.67Kg of L-glutamic acid amlodipine, with a molar yield of 90.07%.

[0053] Example 5

[0054] Add amlodipine (2.5Kg, 7.82mol) to propanol (5.6Kg) solvent, heat and stir, add purified water (1.4Kg) and control the temperature to 81°C. After all the materials are dissolved, add L-glutamic acid (0.9Kg, 6.11mol), continue heating and stirring for 7 hours, cool to room temperature, and keep at 5°C-20°C for 2 hours for crystallization. After the crystallization is completed, filter and rinse the filter cake with the filtrate three times. After the filter cake is dried, 2.98Kg of L-glutamic acid amlodipine is obtained, and the molar yield is 87.62%.

[0055] Example 6

[0056] Add amlodipine (1.4Kg, 3.42mol) to isopropanol (3.5Kg) solvent, heat and stir, add purified water (1.4Kg), control the temperature to 82.5℃, and add L-glutamic acid (0.5Kg, 3.42mol) in batches until all the materials are dissolved. After heating and stirring for 3 hours, cool to room temperature, and keep at 0℃-5℃ for crystallization for 2 hours. After the crystallization is completed, filter by suction, rinse the filter cake twice with the filtrate, and dry the obtained filter cake to obtain 1.56Kg of L-glutamic acid amlodipine, with a molar yield of 82.00%.

[0057] Example 7

[0058] Amlodipine (800.0 g, 1.96 mol) was added to anhydrous ethanol (1800.0 g) solvent, heated and stirred, purified water (400.0 g) was added and the temperature was controlled to 78° C. until all the materials were dissolved, L-glutamic acid (300.0 g, 1.96 mol) was added, and heating and stirring were continued for 7 hours. After cooling to room temperature, crystallization was carried out at 5° C.-20° C. for 2 hours. After the crystallization was completed, suction filtration was performed, and the filter cake was rinsed three times with the filtrate. After the obtained filter cake was dried, 998.0 g of L-glutamic acid amlodipine was obtained, and the molar yield was 91.56%.

[0059] Example 8

[0060] Amlodipine (1000.0 g, 2.45 mol) was added to isopropanol (2800.0 g) solvent, heated and stirred, purified water (800.0 g) was added, the temperature was controlled to 82°C, and after all the materials were dissolved, L-glutamic acid (400.0 g, 3.01 mol) was added in batches, and heating and reflux were continued for 8 hours. After cooling to room temperature, crystallization was carried out at -5°C-5°C for 2 hours. After the crystallization was completed, suction filtration was performed, and the filter cake was rinsed twice with the filtrate. After the obtained filter cake was dried, 1119.8 g of L-glutamic acid amlodipine was obtained, and the molar yield was 82.34%.

[0061] Example 9

[0062] Amlodipine (3.0Kg, 7.34mol) was added to anhydrous ethanol (6.8Kg) solvent, heated and stirred, purified water (2.3Kg) was added, the temperature was controlled to 76°C until all the materials were dissolved, L-glutamic acid (1.3Kg, 8.44mol) was added, and heating and stirring were continued for 13 hours. After cooling to room temperature, crystallization was kept at 0°C-20°C for 8 hours. After the crystallization was completed, suction filtration was performed, and the filter cake was rinsed twice with the filtrate. After the obtained filter cake was dried, 3672.4g of L-glutamic acid amlodipine was obtained, and the molar yield was 90.01%.

[0063] Example 10

[0064] Amlodipine (3.0Kg, 7.34mol) was added to methanol (6.8Kg) solvent, heated and stirred, purified water (2.3Kg) was added, the temperature was controlled to 64°C until all the materials were dissolved, L-glutamic acid (1.3Kg, 9.03mol) was added, and heating and stirring were continued for 13 hours. After cooling to room temperature, crystallization was kept at -15°C-5°C for 8 hours. After the crystallization was completed, suction filtration was performed, and the filter cake was rinsed twice with the filtrate. After the obtained filter cake was dried, 3639.8g of L-glutamic acid amlodipine was obtained, and the molar yield was 89.21%.

[0065] Embodiment 11

[0066] Add amlodipine (1000.0g, 2.45mol) to propanol (2300.0g) solvent, heat and stir, add purified water (1300.0g), raise the temperature to 81°C, until the material is completely dissolved, add L-glutamic acid (400.0g, 2.72mol), heat and reflux for 3 hours, cool to room temperature, and keep at 0°C-5°C for crystallization for 2 hours. After the crystallization is completed, centrifuge and filter until no liquid flows out, and the obtained filter cake is dried to obtain 1186.1g of L-glutamic acid amlodipine, with a molar yield of 87.21%

[0067] Example 12

[0068] Amlodipine (200.0 g, 0.49 mol) was added to anhydrous ethanol (500.0 g) solvent, heated and stirred, purified water (200.0 g) was added, the temperature was controlled to 76°C until all the materials were dissolved, L-glutamic acid (108.0 g, 0.73 mol) was added, heated and refluxed for 1 hour, cooled naturally to room temperature, and kept at 0-10°C for crystallization for 2 hours. After the crystallization was completed, centrifugation was performed until no liquid flowed out, and the obtained filter cake was dried to obtain 234.0 g of L-glutamic acid amlodipine, and the molar yield was 86.03%.

[0069] Embodiment 13

[0070] Amlodipine (100.0 g, 0.24 mol) was added to a propanol (200.0 g) solvent, heated and stirred, purified water (100.0 g) was added, the temperature was controlled to 79°C until all the materials were dissolved, L-glutamic acid (64.8 g, 0.44 mol) was added, and heating and stirring were continued for 10 hours. After cooling to room temperature, the temperature was kept at 0°C-20°C for crystallization for 6 hours. After the crystallization was completed, the filter was filtered, and the filter cake was rinsed twice with the filtrate. After the filter cake was dried, 110.5 g of L-glutamic acid amlodipine was obtained, and the molar yield was 81.23%.

[0071] Comparative Example 1: This comparative example is amlodipine without salt formation.

[0072] Comparative Example 2: This comparative example provides an amlodipine besylate, and the preparation process is as follows:

[0073] Add amlodipine to the ethanol solvent, heat and stir, add purified water, control the temperature to 79°C, add benzenesulfonic acid in batches until the material is completely dissolved, continue heating and reflux for 5 hours, cool to room temperature, and keep at -5°C-5°C for 2 hours for crystallization. After the crystallization is completed, filter, rinse the filter cake twice with the filtrate, and dry the obtained filter cake to obtain amlodipine besylate.

[0074] The product prepared in Example 1 and the products prepared in Comparative Examples 1 and 2 were subjected to stability tests according to the Chinese Pharmacopoeia 2020 Edition, and the results are shown in Table 2.

[0075] Table 2

[0076]

[0077] Embodiment 14

[0078] An L-glutamate amlodipine tablet comprises the following components in parts by weight: 12 parts of L-glutamate amlodipine, 3 parts of a disintegrant, 38 parts of a filler, 2 parts of a lubricant, and 0.5 parts of silicon dioxide.

[0079] Wherein, L-glutamate amlodipine is prepared according to Example 1, the filler is microcrystalline cellulose and anhydrous calcium hydrogen phosphate, the disintegrant is cross-linked sodium carboxymethyl cellulose, and the lubricant is magnesium stearate.

[0080] The preparation method is as follows: adopt the method of direct tableting of dry powder, weigh L-glutamic acid amlodipine and microcrystalline cellulose according to the ratio, pass through an 80-mesh sieve and mix evenly; anhydrous calcium hydrogen phosphate and cross-linked sodium carboxymethyl cellulose are mixed evenly by equal amount addition method, and then mixed with the mixed L-glutamic acid amlodipine and microcrystalline cellulose, pass through an 80-mesh sieve, and finally add magnesium stearate and silicon dioxide, mix for 5 minutes, and directly tablet the powder.

[0081] Embodiment 15

[0082] An L-glutamate amlodipine tablet comprises the following components in parts by weight: 8 parts of L-glutamate amlodipine, 1 part of a disintegrant, 38 parts of a filler, 2 parts of a lubricant, and 0.8 parts of silicon dioxide.

[0083] Wherein, L-glutamic acid amlodipine is prepared by Example 1, the filler is microcrystalline cellulose and anhydrous calcium hydrogen phosphate, the disintegrant is sodium carboxymethyl starch, and the lubricant is magnesium stearate. The preparation method is the same as that of Example 14.

[0084] Example 16

[0085] An L-glutamate amlodipine tablet comprises the following components in parts by weight: 9 parts of L-glutamate amlodipine, 2 parts of a disintegrant, 46 parts of a filler, 2.5 parts of a lubricant, and 0.8 parts of silicon dioxide.

[0086] Wherein, L-glutamic acid amlodipine is prepared by Example 1, the filler is microcrystalline cellulose and anhydrous calcium hydrogen phosphate, the disintegrant is sodium carboxymethyl starch, and the lubricant is sodium stearyl fumarate. The preparation method is the same as that of Example 14.

[0087] Embodiment 17

[0088] An L-glutamate amlodipine tablet comprises the following components in parts by weight: 11 parts of L-glutamate amlodipine, 5 parts of a disintegrant, 52 parts of a filler, 2 parts of a lubricant, and 0.4 parts of silicon dioxide.

[0089] Wherein, L-glutamic acid amlodipine is prepared by Example 1, the filler is microcrystalline cellulose and anhydrous calcium hydrogen phosphate, the disintegrant is sodium carboxymethyl starch, and the lubricant is magnesium stearate. The preparation method is the same as that of Example 14.

[0090] L-Glutamate Amlodipine Tablet Dissolution Test:

[0091] According to the dissolution determination method (HPLC method, ChP2020 General Rule 0512), Examples 14 to 17 were subjected to dissolution determination. The results are shown in Table 3.

[0092] Table 3

[0093]

[0094]

[0095] From the above, it can be seen that the L-glutamate amlodipine prepared by the present invention has good stability, and the L-glutamate amlodipine tablet has good solubility, which is beneficial to improving the bioavailability of L-glutamate amlodipine; the content meets the requirements, the reproducibility is good, and the expected effect is achieved.

[0096] The above description of the embodiments is to facilitate the understanding and use of the invention by those skilled in the art. It is obvious that those skilled in the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative work. Therefore, the present invention is not limited to the above embodiments, and improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the present invention should be within the scope of protection of the present invention.

Claims

1. An L-glutamate amlodipine, characterized in that Its chemical structure is as follows:

2. A method for preparing L-glutamate amlodipine as claimed in claim 1, characterized in that: The method comprises the following preparation steps: dissolving amlodipine in an organic solvent and purified water, adding L-glutamic acid, heating under reflux and then naturally cooling to room temperature, then introducing a refrigerant to keep warm for crystallization, filtering and drying to obtain the L-glutamic acid amlodipine. The reaction route is as follows:

3. The method for preparing L-glutamate amlodipine according to claim 2, characterized in that: The organic solvent is an alcohol solvent, and the alcohol solvent is selected from any one of methanol, ethanol, propanol or isopropanol.

4. The method for preparing L-glutamate amlodipine according to claim 3, characterized in that: The weight ratio of amlodipine to alcohol solvent is 1:2-4, and the weight ratio of amlodipine to purified water is 1: 0.5~1.5, and the molar ratio of amlodipine to L-glutamic acid is 1:0.9~1.

5.

5. The method for preparing L-glutamate amlodipine according to claim 2, characterized in that: The heating reflux time is 1h-18h.

6. The method for preparing L-glutamate amlodipine according to claim 2, characterized in that: The time for the refrigerant to be heat-insulated and crystallized is 2-10 hours, the temperature for the refrigerant to be heat-insulated and crystallized is -20-40°C, and the refrigerant includes any one of hydrocarbons and freon.

7. An amlodipine L-glutamate tablet containing the amlodipine L-glutamate according to claim 1.

8. An L-glutamate amlodipine tablet according to claim 7, characterized in that: The invention comprises the following components in parts by weight: 5 to 12 parts of L-glutamic acid amlodipine, 30 to 60 parts of a filler, 2 to 5 parts of a disintegrant, 0.5 to 2.5 parts of a lubricant and 0.3 to 0.8 parts of silicon dioxide.

9. An L-glutamate amlodipine tablet according to claim 8, characterized in that: The filler includes microcrystalline cellulose and anhydrous calcium hydrogen phosphate; The disintegrant comprises one or more of low-substituted hydroxypropyl cellulose, cross-linked polyvinyl pyrrolidone, cross-linked sodium carboxymethyl cellulose, and sodium carboxymethyl starch; The lubricant includes one or more of sodium stearyl fumarate and magnesium stearate.

10. A method for preparing the L-glutamate amlodipine tablet according to any one of claims 7 to 9, characterized in that: The method comprises the following steps: weighing each weight portion of L-glutamate amlodipine, a filler and a disintegrant, mixing them evenly, sieving, adding a lubricant and silicon dioxide, mixing them evenly, and directly tableting to prepare the L-glutamate amlodipine tablets.

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