Application of deaminotyrosine in preparation of medicine for treating vascular calcification symptom

Abstract

The invention belongs to the field of biological medicine, and particularly relates to application of deaminotyrosine in preparation of a medicine for treating vascular calcification symptoms. The invention finds that deaminotyrosine can significantly reduce the vascular calcification degree of an in-vitro cell model and an in-vivo animal model by inhibiting osteogenic differentiation and calcium salt deposition of vascular smooth muscle cells; therefore, the invention provides a new application of the deaminated tyrosine or pharmaceutically acceptable salt, ester, solvate or prodrug thereof in preparation of drugs for treating vascular calcification symptoms. The invention also provides a pharmaceutical composition, which takes deaminated tyrosine as an active component, and provides a brand new drug choice for clinical prevention and treatment of vascular calcification.

Description

Technical Field

[0001] This invention belongs to the field of biomedicine, specifically relating to the application of deaminotyrosine in the preparation of drugs for treating vascular calcification symptoms. Background Technology

[0002] Vascular calcification is not simply passive calcium salt deposition, but rather an active, cellularly regulated pathological process similar to bone development. It is a very common vascular pathological change in atherosclerosis, hypertension, diabetes, chronic kidney disease (CKD), and aging, characterized by the abnormal deposition of hydroxyapatite crystals in the blood vessel walls, leading to increased vessel wall stiffness and decreased compliance. With the aging population and the rising incidence of metabolic diseases, the prevalence of vascular calcification continues to increase. Epidemiological and clinical studies have confirmed that vascular calcification is an important independent predictor of cardiovascular events and all-cause mortality. Currently, there are no effective or specific drugs to reverse vascular calcification in clinical practice. Current treatment strategies mainly focus on the following aspects:

[0003] 10. Control underlying diseases and risk factors: such as lipid-lowering drugs with statins, blood pressure control with antihypertensive drugs, and strict blood glucose management, etc. However, extensive clinical observations have shown that even after effectively controlling these traditional risk factors, the vascular calcification process continues to progress in many patients, indicating that the mechanism is independent of traditional risk factors.

[0004] 11. Lifestyle interventions: These include dietary control and increased exercise. While these methods are beneficial to overall health, they can only prevent vascular calcification to a certain extent and have limited effect on reversing and treating existing vascular calcification.

[0005] 12. Drug intervention: (1) Phosphate binders: In patients with advanced chronic kidney disease, calcium-containing or non-calcium-containing phosphate binders are often used to control hyperphosphatemia. Calcium-containing phosphate binders may exacerbate positive calcium load and have the risk of promoting vascular calcification; while non-calcium phosphate binders (such as sevelamer) have been observed to be associated with delaying the progression of calcification, but their effects are weak and long-term use is prone to causing gastrointestinal adverse reactions. (2) Bisphosphonates: As a bone resorption inhibitor, they can theoretically interfere with the calcification process, but the actual clinical research results are contradictory to the expected results. The inventors found that they did not show a clear blocking effect in some studies, and long-term use requires attention to their potential impact on bone metabolism (such as atypical fractures, osteonecrosis of the jaw, etc.) and the risk of nephrotoxicity, which limits their widespread application in the field of vascular calcification.

[0006] Deaminotyrosine (DAT), also known as 3-(4-hydroxyphenyl)propionic acid, is a naturally occurring aromatic amino acid metabolite. In the human body, it is produced by the fermentation of dietary fiber by intestinal microorganisms and is also found in some bee products and plants. Existing non-patent literature indicates that DAT possesses various biological activities. For example, some studies have reported that DAT exerts a protective effect against influenza virus infection by regulating the type I interferon signaling pathway; other studies suggest that it may possess certain antioxidant and anti-inflammatory properties. To date, the inventors have found no evidence, either in academic research or patent literature, of any inhibitory or therapeutic effect of DAT on the vascular system, particularly on the key process of osteoblast-like differentiation of vascular smooth muscle cells. Therefore, the potential and value of DAT in the prevention or treatment of vascular calcification remains entirely unexplored and unrecognized. Summary of the Invention

[0007] To address the problems of uncertain efficacy, poor targeting, or significant side effects associated with related technologies, this invention first discloses the application of deaminotyrosine in the preparation of drugs for treating vascular calcification symptoms, and briefly introduces its effects. The specific technical solution is as follows:

[0008] This invention first discloses the use of deaminotyrosine in the preparation of a medicament for treating vascular calcification symptoms, comprising the use of said deaminotyrosine or its pharmaceutically acceptable salt, ester, solvate or prodrug in the preparation of a medicament for treating vascular calcification symptoms.

[0009] Furthermore, the vascular calcification symptoms include, but are not limited to, atherosclerosis-related calcification, diabetic vascular calcification, chronic kidney disease-related vascular calcification, age-related vascular calcification, or metabolic disorder-related vascular calcification.

[0010] Furthermore, the deaminotyrosine exerts its therapeutic effect by inhibiting osteoblast-like differentiation or calcium salt deposition in vascular smooth muscle cells.

[0011] Furthermore, the inhibition of osteoblast-like differentiation of smooth muscle cells includes downregulating the expression of osteogenic-related markers Runx2, ALP, or OPN.

[0012] The present invention also provides a pharmaceutical composition for treating or preventing symptoms of vascular calcification, the pharmaceutical composition comprising a therapeutically effective amount of an active ingredient; said active ingredient is deaminotyrosine or a pharmaceutically acceptable salt thereof.

[0013] Furthermore, the deaminotyrosine or a pharmaceutically acceptable salt thereof comprises a salt formed therefrom with an inorganic or organic base.

[0014] Furthermore, the inorganic base is a sodium base, potassium base, calcium base, or magnesium base; the organic base is meglumine, diethanolamine, or choline.

[0015] Furthermore, the unit dosage form of the pharmaceutical composition contains 0.1 mg to 5000 mg of the deaminotyrosine.

[0016] Furthermore, the dosage form of the pharmaceutical composition is an oral dosage form or an injectable dosage form, the dosage form comprising the deaminotyrosine and a pharmaceutically acceptable carrier or excipient.

[0017] Furthermore, when the dosage form is a tablet, the pharmaceutically acceptable carrier includes one or more of a diluent, a binder, a disintegrant, and a lubricant; when the dosage form is an injection, the pharmaceutically acceptable carrier includes one or more of a solvent, a pH adjuster, an osmotic pressure adjuster, and a stabilizer.

[0018] Furthermore, the oral dosage form is a tablet, capsule, granule, or oral liquid; the injectable dosage form is an intravenous injection or an intraperitoneal injection.

[0019] This invention addresses the problems of uncertain efficacy, poor targeting, or significant side effects associated with related technologies by disclosing the application of deaminotyrosine in the preparation of drugs for treating vascular calcification symptoms, and provides a novel pharmaceutical use for deaminotyrosine or its pharmaceutically acceptable form.

[0020] Compared with related technologies, the present invention has at least the following beneficial effects: I. Novel Application in the Treatment of Vascular Calcification: This invention is the first to discover and confirm that deaminotyrosine has a novel pharmacological activity in inhibiting vascular calcification, opening up a completely new application field.

[0021] II. Significantly Improved Therapeutic Effect: This invention has demonstrated through in vitro cell experiments and in vivo animal models that deaminotyrosine can significantly reduce β-glycerophosphate-induced vascular smooth muscle cell calcification and effectively inhibit calcium salt deposition in a mouse vascular calcification model induced by a high-phosphorus diet.

[0022] III. Highly targeted specific treatment: This invention utilizes the mechanism of action of deaminotyrosine to target the core link of vascular calcification—osteoblastic transdifferentiation of vascular smooth muscle cells, thereby intervening in the pathological process from the root.

[0023] IV. High safety profile: Deaminotyrosine is an endogenous metabolite with good biocompatibility and low toxicity, making it highly safe for potential clinical applications in the treatment or prevention of vascular calcification. Attached Figure Description

[0024] The accompanying drawings, which form part of this application, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an undue limitation of the invention. In the drawings:

[0025] Figure 1 The effect of DAT on β-glycerophosphate (β-GP)-induced calcification of rat vascular smooth muscle cells (A7r5), where: (A) is the staining result of calcium nodules of A7r5 cells (Alizarin Red S staining) under different concentrations of DAT treatment; (B) is the bar chart of quantitative analysis of ALP staining results (**p<0.01 compared with the model group).

[0026] Figure 2 Schematic diagram of the effect of DAT on a 1,25-dihydroxyvitamin D3-induced mouse vascular calcification model. Figure 3 Effects of DAT on the levels of osteogenic markers Runx2 and osteocalcin protein in vascular smooth muscle cells. Detailed Implementation

[0027] To enable those skilled in the art to better understand the present invention, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of the present invention.

[0028] It should be noted that the terms "comprising" and "having" and any variations thereof in the specification, claims and accompanying drawings of this invention are intended to cover non-exclusive inclusion, such as a process, method, system, product or device that includes a series of steps or units, which is not necessarily limited to those steps or units explicitly listed, but may include other steps or units not explicitly listed or inherent to such processes, methods, products or devices.

[0029] It should be noted that, unless otherwise specified, the embodiments and features described in this application can be combined with each other. The present invention will now be described in detail with reference to the accompanying drawings and embodiments.

[0030] Example 1: Inhibitory effect of DAT on calcification of vascular smooth muscle cells in vitro 13. Cell Culture and Grouping (14) Cell resuscitation and culture: Take out the frozen A7r5 cells (ordered from Pronosei) and thaw them rapidly in a 37°C water bath. Transfer the cell suspension to a 15 mL centrifuge tube, slowly add 3 mL of complete culture medium and mix well. Centrifuge at 1000 rpm for 5 min and discard the supernatant. Add fresh complete culture medium, mix well by pipetting, and transfer to a culture flask. Place the flask in a CO2 incubator for culture. Set the incubator parameters as follows: temperature 37°C, 5% CO2, 95% saturated humidity.

[0031] (15) Cell passage and medium change: When the adherent cells in the culture flask reach about 80% confluence, discard the original culture medium and rinse with PBS. Add 1 mL of 0.25% trypsin and incubate for about 1 min. Observe under an inverted microscope. When the spindle-shaped cells tend to become rounded and gradually separate, the cell digestion is complete. Add 1 mL of complete culture medium to stop digestion. Pipe the cells from top to bottom at the bottom of the culture flask to detach them. After that, transfer them to centrifuge tubes. Centrifuge at 1000 × g for 5 min. Carefully remove the centrifuge tubes and discard the supernatant. Add fresh culture medium to the bottom cell clusters, mix well, and divide into 2-3 portions depending on the cell mass. Transfer to new culture flasks. Add complete culture medium to each flask to make up to 8 mL of culture medium, gently shake well, and place in an incubator to continue culturing. After two days, discard the original culture medium and add fresh culture medium. Pay attention to the cell morphology and growth status. When the cells reach about 80% confluence, they can be passaged again.

[0032] (16) Experimental grouping: Cells from passages 3-5 in good growth condition were digested with 0.25% trypsin and then divided into groups of 2 × 10⁻⁶ cells per well. 4 Cells were seeded at a density of 1000 cells / well in 24-well plates. After complete cell adhesion, the cells were randomly divided into the following four groups: control group: replaced with normal complete medium containing 10% FBS; model group: replaced with calcification induction medium containing 10% FBS and 3 mM β-GP; low-dose DAT group: DAT was added to the calcification induction medium to a final concentration of 4 μM; high-dose DAT group: DAT was added to the calcification induction medium to a final concentration of 7 μM.

[0033] (17) Drug preparation: Weigh 2.6 mg of DAT powder, dissolve it in 1 mL of PBS to prepare a 200 mM stock solution, and adjust the pH to 7.4 with 1 M NaOH. Store at -20℃. When using, dilute stepwise with complete culture medium to the required working concentration. Set up 6 replicates per group, replace with fresh complete culture medium every 2 days, and culture continuously for 10 days.

[0034] It should be noted that the complete culture medium is a 10% complete culture medium, which is prepared as follows: fetal bovine serum accounts for 10% of the culture medium, and the antibiotic solution accounts for 1%. After calculating based on the total volume, the serum and antibiotic solution are added to DMEM high glucose culture medium in sequence, and the mixture is thoroughly mixed by pipetting. It is then stored at 4°C.

[0035] 18. Alizarin Red S staining (19) Preparation of dye solution: Weigh 1.0 g of Alizarin Red S powder, dissolve it in 50 mL of ultrapure water, adjust the pH to 4.2 with glacial acetic acid, make up to 100 mL, filter with a 0.22 μm filter membrane, and store at 4°C in the dark.

[0036] (20) Staining procedure: Take cultured cells, discard the culture medium, add 1 mL of pre-cooled PBS to each well, and gently shake and wash 3 times, 1 min each time; add 2 mL of 4% paraformaldehyde (dissolved in PBS) to each well and fix at room temperature for 30 min; after removing the fixative, gently wash 2-3 times with PBS to ensure that the fixative is completely removed; add 500 μL of freshly prepared 2% Alizarin Red S staining solution (pH 4.2) to each well and incubate at room temperature in the dark for 30 min; after removing the staining solution, wash thoroughly with ultrapure water 5-6 times until the aqueous phase is clear to remove non-specific staining; add 2 mL of PBS to each well and observe the staining effect under an inverted microscope.

[0037] (21) Analysis of staining results: The staining results are as follows Figure 1 As shown in Figure (A), a large number of calcium nodules were observed in the model group. The number of calcium nodules in the low-dose DAT treatment group and the high-dose DAT treatment group decreased to different degrees. The comparison showed that it was concentration-dependent.

[0038] 22. Alkaline phosphatase (ALP) activity staining (23) Reagent preparation: Prepare substrate buffer, colorimetric solution and other reagents according to the instructions of ALP staining kit (G1480 Solarbio).

[0039] (24) Cell fixation: Discard the culture medium from the cultured cells and rinse twice with pre-cooled PBS; fix the cell samples with 4% paraformaldehyde at room temperature for 15 min, and rinse three times with PBS for 5 min each time.

[0040] (25) Permeabilization treatment: After treating cells with 0.1% Triton X-100 for 5-10 min, rinse twice with PBS for 2 min each time.

[0041] (26) Incubation of substrate: Mix the prepared substrate buffer and the color development solution evenly, drop it onto the cell sample, and incubate in a 37°C incubator for 30 min; after incubation, rinse the sample with distilled water to terminate the color development reaction.

[0042] (27) Dehydration and mounting: Dehydrate with gradient ethanol (e.g., 70%, 80%, 95%) for 5 min each time, and then clear with xylene for 5 min. After mounting, observe the area with high ALP activity under a microscope. The area will appear dark blue-purple.

[0043] (28) Results analysis: The staining product was dissolved in 1% sodium dodecyl sulfate (SDS) solution in each well, and the absorbance (OD) was measured at a wavelength of 620 nm. 620 (Value). Experimental results are as follows: Figure 1 As shown in (B), ALP activity in the model group was significantly increased compared with that in the control group. Compared with the model group, both the low-dose and high-dose DAT groups could reduce ALP activity in a dose-dependent manner, providing a basis for the use of DAT in the treatment of vascular calcification.

[0044] Example 2: The therapeutic effect of DAT on vascular calcification in mice in vivo 29. Animal Adaptation and Grouping: SPF-grade C57BL / 6J mice were purchased from the Experimental Animal Center of Hubei University of Medicine. All animal experiments were conducted in accordance with the regulations of the institution's Animal Care and Use Committee. Mice were acclimatized in an SPF-grade animal facility for one week (12 / 12 h light / dark cycle, free access to water and food), and then randomly divided into three groups: Model group: induced by 1,25-dihydroxyvitamin D3; Control group: no modeling treatment; DAT treatment group: induced by 1,25-dihydroxyvitamin D3 and treated with DAT.

[0045] 30. Model establishment: Mice in the model group and the DAT treatment group were injected intraperitoneally with 1,25-dihydroxyvitamin D3 solution at fixed times every day.

[0046] It should be noted that the 1,25-dihydroxyvitamin D3 solution is prepared as follows: accurately weigh 2.5 mg of 1,25-dihydroxyvitamin D3, dissolve it in 125 μL of anhydrous ethanol, add 4875 μL of sesame oil, vortex until completely dissolved and clear, and prepare a stock solution of 500 μg / mL.

[0047] 3. Dosing regimen: From the first day of modeling, mice in the DAT treatment group were injected intraperitoneally with DAT solution (50 mg / kg) daily, while mice in the model group and control group were injected intraperitoneally with an equal volume of physiological saline daily.

[0048] It should be noted that the preparation method of the DA-T solution is as follows: weigh 450 mg of DAT powder, dissolve it with an appropriate amount of physiological saline, adjust the pH to 7.4 with 1 M NaOH, and finally make up the volume to 90 mL with physiological saline to obtain a DAT solution with a concentration of 5 mg / mL.

[0049] 31. Sample Collection: Twenty-four hours after the last administration, mice were deeply anesthetized by intraperitoneal injection of 1% sodium pentobarbital (50 mg / kg). The thoracic cavity of the mice was opened to expose the heart, and a cannula was inserted into the ascending aorta through the left ventricle. 50 mL of pre-cooled PBS was rapidly perfused to flush out the blood. Using fine microscissors and forceps, the aorta from the aortic arch to the bifurcation of the iliac artery was completely separated, placed on ice in PBS, and the fat and connective tissue around the blood vessels were carefully dissected. Each aorta was fixed in 4% paraformaldehyde for staining analysis.

[0050] 32. Von Kossa dyeing: (33) Dehydration: Use xylene I for 5 min, xylene II for 5 min, xylene III for 5 min, anhydrous ethanol for 1 min, 95% ethanol for 1 min, 75% ethanol for 1 min, and distilled water for 1 min.

[0051] (34) Add sufficient 5% Von Kossa silver solution (Von Kossa kit, G3282, Solarbio), place under strong light for 30 min, wash with water for 1 min; add hyoscine solution for 2 min, wash with distilled water for 2 min.

[0052] (35) After dehydration with 95% ethanol for 1 min and anhydrous ethanol for 1 min, xylene was used for dewaxing. The solution was cleared, and the solution was sealed with neutral resin. The staining results were observed under a microscope.

[0053] (36) Results analysis: The staining results are as follows Figure 2 As shown, a large number of Von Kossa positive stainings were observed in the aorta of the model group mice, indicating significant aortic calcification. The degree of calcification in the DAT treatment group was similar to that in the control group, indicating that DAT significantly weakens vascular calcification. The mouse model achieved good expected experimental results, fully demonstrating the potential of DAT in the treatment of vascular calcification.

[0054] Example 3: Effects of DAT on Osteogenesis-Related Gene Expression Proteins were extracted from cells in each group in Example 1, and the protein expression levels of key osteogenic transcription factors Runx2, osteocalcin, and osteopeotin were detected by Western blot.

[0055] 37. Protein Sample Preparation (38) Using the cells cultured in Example 1, discard the culture medium, rinse twice with pre-cooled PBS, and after washing, absorb as much of the residual PBS in the well as possible.

[0056] (39) Prepare cell lysis buffer according to the ratio. Add 100 μL of RIPA lysis buffer containing 1% protease inhibitor and 1% phosphatase inhibitor to each well. After lysing on ice for 30 min, scrape off the cells from each well and collect them into a 1.5 mL centrifuge tube. Centrifuge at 12000×g and 4 ℃ for 10 min and collect the supernatant to obtain the sample protein.

[0057] 40. Glue making Select a 1.0 mm glass plate, carefully clean it with a test tube brush and detergent, and rinse thoroughly with water. Align the glass plates, with the shorter side facing inward, and insert them into both sides of the gel casting apparatus. Place the apparatus on the base and tighten the knobs on both sides simultaneously to secure the glass plates. To check for leaks, fill the glass plate with distilled water. Observe for a few minutes; if the liquid level does not drop, the seal is good. At this point, pour out the water and invert the apparatus to dry. Prepare the gel casting solution according to the appropriate concentration based on the protein molecular weight. Take a small beaker and add various reagents in sequence to prepare the separating gel. After adding TEMED and shaking well, immediately pour the gel. When pouring, use a pipette to draw up the gel solution and slowly add it along the side of the glass plate, avoiding the formation of air bubbles. Add 95% ethanol to the top layer of the gel solution for liquid sealing. Let it stand at room temperature on a horizontal surface for about 30 minutes. When a horizontal zigzag line is observed between the water and the gel, it indicates that the separating gel has solidified. At this point, pour off the upper layer of ethanol; any remaining liquid can be absorbed with filter paper. Take a small beaker and add the required reagents to prepare a 5% stacking gel. Fill the remaining space in the glass plate with the stacking gel in the same way. Insert a dry, clean comb horizontally into the stacking gel and let it stand at room temperature until it solidifies. After solidification, hold both ends of the comb with your hands and gently pull it upwards. Transfer the glass plate into the electrophoresis tank and add electrophoresis buffer to submerge it.

[0058] 41. Sample loading and electrophoresis Remove the samples and pre-stained protein markers from the refrigerator beforehand, thaw them, and shake to mix. Add the markers and samples as needed, determining the loading volume based on 30-50 μg of protein per well and the desired development effect. Add the samples gently to avoid spilling into other wells. Connect the positive and negative electrodes to the electrophoresis apparatus and turn on the power. Set the voltage and start electrophoresis. Electrophoresis is complete when the markers are clearly separated and the blue bromophenol blue band is approximately 1 cm from the bottom of the gel.

[0059] 42. Transfer membrane Prepare the transfer buffer in advance, and cut the filter paper and PVDF membrane. Activate the PVDF membrane by immersing it in methanol for approximately 1 minute, then transfer it to the transfer buffer along with the filter paper. After electrophoresis, remove the glass plate, gently pry it open, and cut the gel according to the molecular weight of the protein to be measured, referring to the marker position. Keep the gel moist throughout the process. Construct a "sandwich" structure on the electrophoresis apparatus clamps, placing three layers of filter paper at the bottom, followed by the gel, PVDF membrane, and the three layers of filter paper in sequence. Gently roll the gel with a glass rod to remove air bubbles, and pour the transfer buffer into the electrophoresis tank. Close the lid, set the current and time, and keep the electrophoresis tank in an ice bath during the transfer process to prevent excessive heat.

[0060] 5. Blocking and incubating antibodies Prepare the defatting blocking buffer in advance. After the transfer is complete, turn off the power, remove the PVDF membrane with tweezers, immerse it in the blocking buffer, and rinse it on a shaker at 90 rpm / min for 1.5 h. After blocking, transfer the membrane to PBST buffer and rinse it on a shaker at 120 rpm / min for 10 min / 4 times. Then, place the PVDF membrane in the prepared primary antibody solution. Incubate at 4 ℃. After the incubation period, remove the PVDF membrane, place it in PBST buffer, rinse it on a shaker, and then transfer it to the prepared secondary antibody solution, immersing the PVDF membrane. Set the shaker to 80 rpm / min and incubate for 2 h.

[0061] 43. Development and Image Analysis After incubation, rinse with PBST buffer for 10 min, three times in total. Take an EP tube covered with aluminum foil and prepare the luminescent solution under dark conditions. Place the rinsed PVDF membrane in the dark compartment of a gel imaging system, and evenly cover the membrane surface with the luminescent solution. React in the dark for approximately 1 min, then expose for imaging and capture and save the images. The experimental results are shown in the image below. Figure 3 As shown. By Figure 3 As can be seen, compared with the control group, the protein expression levels of Runx2 and Osteocalcin in the model group cells were significantly upregulated. Furthermore, compared with the model group, the DAT treatment groups (4 μM and 7 μM) dose-dependently inhibited the protein expression of these three key osteogenic markers, not only intervening in the progression of vascular calcification at its root but also revealing the safety of DAT as an endogenous metabolite, providing a basis for the use of DAT in specific targeted therapy for vascular calcification symptoms.

[0062] The above description represents the preferred embodiments of the present invention. It should be noted that all reagents and materials used in the embodiments of the present invention, unless otherwise specified, are standardized products that can be obtained through conventional commercial channels. However, it should be understood that those skilled in the art can choose equivalent products from other suppliers, which does not depart from the scope of protection of the present invention. For those skilled in the art, several improvements and modifications can be made without departing from the principles described in the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. Use of a desaminotyrosine for the preparation of a medicament for the treatment of a symptom of vascular calcification, characterized in that, Use of desaminotyrosine or a pharmaceutically acceptable salt, ester, solvate or prodrug thereof in the manufacture of a medicament for treating a vascular calcification condition.

2. Use according to claim 1, characterized in that, The vascular calcification condition includes, but is not limited to, atherosclerosis-related calcification, diabetic vascular calcification, chronic kidney disease-related vascular calcification, aging-related vascular calcification or metabolic disorder-related vascular calcification.

3. The use according to claim 1, characterized in that, The desaminotyrosine exerts a therapeutic effect by inhibiting osteogenic differentiation or calcium salt deposition of vascular smooth muscle cells.

4. Use according to claim 3, characterized in that, The inhibition of osteogenic differentiation of smooth muscle cells includes down-regulation of expression of osteogenesis-related markers Runx2, ALP or OPN.

5. A pharmaceutical composition for treating or preventing a symptom of vascular calcification, characterized by, The pharmaceutical composition comprises a therapeutically effective amount of an active ingredient; the active ingredient is desaminotyrosine or a pharmaceutically acceptable salt thereof.

6. The pharmaceutical composition of claim 5, wherein, The desaminotyrosine or a pharmaceutically acceptable salt thereof comprises a salt thereof with an inorganic base or an organic base; preferably, the inorganic base is a sodium base, a potassium base, a calcium base or a magnesium base; the organic base is meglumine, diethanolamine or choline.

7. The pharmaceutical composition of claim 5, wherein, The unit dosage form of the pharmaceutical composition contains 0.1 mg to 5000 mg of the desaminotyrosine.

8. The pharmaceutical composition of claim 7, wherein, The dosage form of the pharmaceutical composition is an oral dosage form or an injection dosage form; the dosage form comprises the active ingredient and a pharmaceutically acceptable carrier or excipient.

9. The pharmaceutical composition of claim 8, wherein, When the dosage form is an oral dosage, the pharmaceutically acceptable carrier includes one or more of a diluent, a binder, a disintegrant and a lubricant; when the dosage form is an injection, the pharmaceutically acceptable carrier includes one or more of a solvent, a pH regulator, an osmotic pressure regulator and a stabilizer.

10. The pharmaceutical composition of claim 8, wherein, The oral dosage form is a tablet, a capsule, a granule or an oral liquid; the injection dosage form is an intravenous injection or an intraperitoneal injection.

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