Application of L-palmitoyl carnitine in preparation of antithrombotic drugs and / or anti-inflammatory drugs

Abstract

The invention provides application of L-palmitoyl carnitine in preparation of antithrombotic drugs and / or anti-inflammatory drugs, and belongs to the technical field of biological medicines. The L-palmitoyl carnitine (L-PC) is used as an endogenous regulator of a fibrinolysis system, can exert the functions of resisting thrombus and inhibiting inflammatory reaction by enhancing the enzymatic activity of a urokinase-type plasminogen activator (uPA), has a remarkable treatment effect on thrombosis and thrombotic diseases, has a relatively low bleeding risk, and can be used for preparing a medicine for treating thrombosis and thrombotic diseases. The compound is expected to be applied as an anti-thrombotic and anti-inflammatory drug.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of L-palmitoylcarnitine in the preparation of antithrombotic drugs and / or anti-inflammatory drugs. Background Art

[0002] L-Palmitoylcarnitine (L-PC), also known as hexadecylcarnitine, is an acylcarnitine and a long-chain acyl fatty acid derivative of carnitine. During the fatty acid oxidation process, it can promote the transport of acyl groups, organic acids and fatty acids from the cytoplasm to the mitochondria so that these substances can be broken down and produce energy.

[0003] Currently, there is no report on the use of L-PC in the preparation of anti-thrombotic and anti-inflammatory drugs. Summary of the invention

[0004] The purpose of the present invention is to provide the use of L-palmitoyl carnitine in the preparation of antithrombotic drugs and / or anti-inflammatory drugs. L-palmitoyl carnitine has a significant therapeutic effect on thrombosis and thrombotic diseases.

[0005] The present invention provides the use of L-palmitoyl carnitine in the preparation of antithrombotic drugs and / or anti-inflammatory drugs, wherein the chemical structural formula of the L-palmitoyl carnitine is as shown in Formula I;

[0006]

[0007] Preferably, the anti-thrombotic effect includes preventing, treating or alleviating thrombotic diseases; and the anti-inflammatory effect includes alleviating the inflammatory response caused by ischemia-reperfusion.

[0008] Preferably, the thrombotic disease includes at least one of venous thrombosis, cerebral infarction and acute myocardial infarction.

[0009] Preferably, the thrombus includes arterial thrombus and / or venous thrombus.

[0010] Preferably, the venous thrombosis comprises cortical vein thrombosis.

[0011] Preferably, the cortical vein thrombosis comprises photochemically induced cortical vein thrombosis.

[0012] Preferably, the dosage form of the drug includes an oral preparation or an injection.

[0013] The present invention also provides the use of L-palmitoylcarnitine in preparing an enhancer of urokinase-type plasminogen activator, wherein the chemical structural formula of the L-palmitoylcarnitine is as shown in Formula I;

[0014] The present invention also provides the use of L-palmitoyl carnitine in preparing products for maintaining vascular health. The chemical structural formula of the L-palmitoyl carnitine is shown in Formula I.

[0015] Preferably, the maintenance of blood vessel health is achieved by anticoagulation; the product includes food, health care products, nutritional supplements or medicines.

[0016] The present invention provides the use of L-palmitoylcarnitine (L-PC) in the preparation of antithrombotic drugs and / or anti-inflammatory drugs. As an endogenous regulator of the fibrinolytic system, L-PC can enhance the enzyme activity of urokinase-type plasminogen activator (uPA) to exert anti-thrombotic and anti-inflammatory response functions, has a significant therapeutic effect on thrombosis and thrombotic diseases, and has a lower risk of bleeding, and is expected to be used as an antithrombotic and anti-inflammatory drug. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.

[0018] Figure 1 This is the experimental diagram of L-Palmitoylcarnitine plasma recalcification (PRT);

[0019] Figure 2 The time corresponding to the maximum reaction rate of L-Palmitoylcarnitine plasma recalcification experiment;

[0020] Figure 3 This is the result diagram of the effect of L-Palmitoylcarnitine on prothrombin time (PT);

[0021] Figure 4 This is the result diagram of the effect of L-Palmitoylcarnitine on activated partial thromboplastin time (APTT);

[0022] Figure 5 This is the result of the enzyme kinetics experiment to detect the effect of L-Palmitoylcarnitine on u-PA (urokinase);

[0023] Figure 6 This is the result diagram of SPR detection of the interaction between L-Palmitoylcarnitine and u-PA;

[0024] Figure 7This is a graph showing the results of a hemolytic activity experiment of L-Palmitoylcarnitine;

[0025] Figure 8 This is a graph showing the results of the toxicity test of L-Palmitoylcarnitine on Hek-293T cells;

[0026] Fig. 9 This is a graph showing the effect of L-Palmitoylcarnitine on photochemically induced cortical thrombosis;

[0027] Fig.10 This is a diagram showing the effect of L-Palmitoylcarnitine in a mouse tail bleeding model;

[0028] Fig.11 This is a diagram showing the effect of L-Palmitoylcarnitine in a cerebral hemorrhage model;

[0029] Fig.12 This is a graph showing the effect of L-Palmitoylcarnitine on inflammatory factors. DETAILED DESCRIPTION

[0030] The present invention provides the use of L-palmitoylcarnitine (L-PC) in the preparation of antithrombotic drugs and / or anti-inflammatory drugs, wherein the chemical structural formula of the L-palmitoylcarnitine is shown in Formula I;

[0031]

[0032] As an endogenous regulator of the fibrinolytic system, L-PC can exert its anti-thrombotic and anti-inflammatory functions by enhancing the enzymatic activity of urokinase-type plasminogen activator (uPA). It has significant therapeutic effects on thrombosis and thrombotic diseases, and has a lower risk of bleeding. It is expected to be used as an anti-thrombotic and anti-inflammatory drug.

[0033] In the present invention, the molecular formula of L-PC is C 23 H 45 NO4, MedChemExpress, HY-113147A, molecular weight 436.07 g / mol. L-PC is synthesized from palmitoyl CoA and L-carnitine (LC) under the catalysis of carnitine palmitoyltransferase 1. Increased levels of L-PC can be achieved by taking LC or adding L-PC itself.

[0034] In the specific implementation of the present invention, the anti-thrombotic effect includes preventing, treating or alleviating thrombotic diseases.

[0035] In the specific implementation of the present invention, the thrombotic disease includes at least one of venous thrombosis, cerebral infarction and acute myocardial infarction.

[0036] In the specific implementation of the present invention, the thrombus includes venous thrombus and / or arterial thrombus.

[0037] In the specific implementation of the present invention, the venous thrombosis includes cortical venous thrombosis, which is a special type of cerebral venous thrombosis in cerebral thrombosis. L-PC can reduce the photochemically induced cortical venous thrombosis in mice.

[0038] In a specific implementation of the present invention, the cortical vein thrombosis includes photochemically induced cortical vein thrombosis.

[0039] In the present invention, the photochemical induction includes irradiating the designated area with a 562 nm yellow-green laser (model R-LG561-100-A5, RWD, China) at a power of 15.5 mW for 6 min.

[0040] In the specific implementation of the present invention, the anti-inflammatory includes reducing the inflammatory response caused by ischemia-reperfusion, and further reducing the inflammatory response caused by ischemia-reperfusion during the reperfusion stage. L-PC can effectively alleviate the inflammatory response caused by ischemia-reperfusion, thereby significantly reducing the brain damage caused thereby.

[0041] In the specific implementation of the present invention, the dosage form of the drug includes oral preparations or injections.

[0042] The present invention also provides the use of L-palmitoyl carnitine in preparing an enhancer of urokinase-type plasminogen activator (uPA). The chemical structural formula of the L-palmitoyl carnitine is shown in Formula I.

[0043] In the present invention, L-PC directly interacts with uPA to enhance the activity of uPA, and the equilibrium dissociation constant (KD) is 2.32×10 -9 M.

[0044] The present invention also provides the use of L-palmitoyl carnitine in preparing products for maintaining vascular health. The chemical structural formula of the L-palmitoyl carnitine is shown in Formula I.

[0045] In the specific implementation process of the present invention, the maintenance of blood vessel health is achieved through anti-coagulation; the product includes food, health care products, nutritional supplements or medicines.

[0046] To further illustrate the present invention, the application of L-palmitoylcarnitine provided by the present invention in the preparation of antithrombotic drugs and / or anti-inflammatory drugs is described in detail below in conjunction with the accompanying drawings and examples, but they should not be construed as limiting the scope of protection of the present invention.

[0047] Example 1

[0048] 1. Plasma coverage experiment

[0049] 1) Take fresh venous blood from a healthy person and place it in a centrifuge tube containing sodium citrate, mix well, centrifuge at 3300r / min for 15min, collect the upper layer (plasma, yellow) and transfer it to a 1.5mL centrifuge tube for later use.

[0050] 2) Experimental groups 1 to 4 were set up as follows:

[0051] Experimental group 1: 19 μL of plasma obtained in step 1) and 1 μL of PBS (i.e., L-PC compound concentration was 0 μM) were mixed in 40 μL of HEPES buffer (20 mM HEPES, 150 mM NaCl, pH 7.4), and 3 replicates were set;

[0052] Experimental group 2: 19 μL of plasma obtained in step 1) and 1 μL of 12.5 μM L-PC solution (solvent: PBS, the same below) were mixed in 40 μL of HEPES buffer (20 mM HEPES, 150 mM NaCl, pH 7.4) and three replicates were set up.

[0053] Experimental group 3: 19 μL of plasma obtained in step 1) and 1 μL of 25 μM L-PC solution were mixed in 40 μL of HEPES buffer (20 mM HEPES, 150 mM NaCl, pH 7.4) and three replicates were set up.

[0054] Experimental group 4: 19 μL of plasma obtained in step 1) and 1 μL of 50 μM L-PC solution were mixed in 40 μL of HEPES buffer (20 mM HEPES, 150 mM NaCl, pH 7.4) and three replicates were set up.

[0055] 3) Add samples from experimental groups 1 to 4 to a 96-well ELISA plate, and place the plate in a 37°C incubator for 10 minutes. Immediately after incubation, add 40 μL of HEPES buffer solution containing 25 mM CaCl2 that has been preheated to 37°C. Set up the kinetic program: absorbance is 650 nm, measured every 30 seconds, and the time is 30 minutes. Calculate the coagulation time by measuring the time for the absorbance to increase by half. Compare and analyze the coagulation time of the experimental group with that of the control group to detect the effect of L-PC on the plasma recalcification experiment. The results are as follows: Figure 1 and Figure 2 As shown by Figure 1 , Figure 2It can be seen that L-PC significantly prolongs the plasma recalcification time, and this prolongation is concentration-dependent, indicating that L-PC has an anticoagulant effect.

[0056] 2. Activated partial thromboplastin time (APTT) test

[0057] APTT is a screening method used to evaluate the functionality and integrity of the intrinsic coagulation pathway and the common pathway, with a particular focus on kininogen, prekallikrein, XII, XI, IX, VIII, X, V, and thrombin. In the experiment, the APTT kit (GMS10178.2) provided by Genmed (USA) and the prothrombin time (PT) kit (STY50101) provided by Steellex (China) were used, and the manufacturer's guidelines were strictly followed. Kinetic analysis was performed at a wavelength of 650nm using the microplate reader Epoch109 produced by Bio Tek (USA) to monitor the progress of the APTT experiment. The specific experimental steps are as follows:

[0058] The experimental group and the control group (negative control, NC) were set up as follows:

[0059] The experimental groups are divided into the following experimental groups 1 to 4:

[0060] Experimental group 1: 19 μL of plasma obtained in step 1) and 1 μL of L-PC solution (solvent: PBS, the same below) with a concentration of 6.25 μM L-PC were mixed in 40 μL of HEPES buffer (20 mM HEPES, 150 mM NaCl, pH 7.4), and three replicates were set up;

[0061] Experimental group 2: 19 μL of plasma obtained in step 1) and 1 μL of L-PC solution with a concentration of 12.5 μM L-PC were mixed in 40 μL of HEPES buffer (20 mM HEPES, 150 mM NaCl, pH 7.4) and three replicates were set up.

[0062] Experimental group 3: 19 μL of plasma obtained in step 1) and 1 μL of 25 μM L-PC solution were mixed in 40 μL of HEPES buffer (20 mM HEPES, 150 mM NaCl, pH 7.4) and three replicates were set up.

[0063] Experimental group 4: 19 μL of plasma obtained in step 1) and 1 μL of 50 μM L-PC solution were mixed in 40 μL of HEPES buffer (20 mM HEPES, 150 mM NaCl, pH 7.4) and three replicates were set up.

[0064] NC group: HEPES buffer, set up 3 replicates.

[0065] 50 μl of normal plasma was mixed with 5 μl of solution from experimental groups 1 to 4 and NC group, respectively, and incubated in a 37°C water bath for 3 min. Immediately, 50 μl of preheated CaCl2 solution was added to the incubated samples and mixed. The absorbance (OD650) was recorded at a wavelength of 650 nm using an ELISA reader.

[0066] The results of verifying the effects of experimental groups 1 to 4 and NC group on prothrombin time (PT) are shown in Figure 3 The results of verifying the effects of experimental groups 3 and 4 and NC group on activated partial thromboplastin time (APTT) are shown in Figure 4 .

[0067] Depend on Figure 3 and Figure 4 It can be seen that the experimental group with L-PC did not show a significant delay in the APTT and PT experiments. 0, 25, and 50 μM L-PC had no effect on APTT; and 0, 6.25, 12.5, 25, and 50 μM L-PC had no effect on PT. This indicates that L-PC does not exert an anticoagulant effect through the intrinsic or extrinsic coagulation pathway. This finding is consistent with the observation that L-PC prolongs the recalcification time in the plasma recalcification experiment.

[0068] 3. Enzyme kinetics assay

[0069] The enzyme kinetics experiment was performed using a luminescent substrate to verify that L-PC has an activating effect on the enzyme in the coagulation pathway. The enzyme in the experiment is urokinase-like plasminogen activator (uPA), and the effect of L-PC on the activity of u-PA. The specific experimental steps are as follows:

[0070] The effect of L-PC on u-PA activity was detected by chromogenic substrate: 2.36nM U-PA (urokinase plasminogen activator, HY-P71050, MedChemExpress, USA) and different concentrations of L-PC (0, 12.5, 25, 50, 100 μM) were added to 50 μL PBS and then incubated at 37°C for 5 min, followed by the addition of 50 μL 433 μM HD-isoleucyl-L-prolyl-L-arginine-p-nitroaniline dihydrochloride (Chromogenix S-2288TM, Diapharma, USA) for u-PA color reaction. The absorbance was immediately monitored at 405 nm for 30 min using a Gen5 microplate reader (Epoch, Bio-Tech, USA).

[0071] Results Figure 5 , Figure 5 The system with 0 μM L-PC was recorded as NC. From the changes in the absorbance of each group detected at OD 405 nm, it can be seen that compared with the NC group, 12.5 μM, 25 μM, 50 μM and 100 μM L-PC all promoted the activity of u-PA, and had a concentration effect, showing an anticoagulant effect.

[0072] 4. SPR molecular interaction experiment between LP and u-PA

[0073] The surface plasmon resonance (SPR) technique was used to examine the relationship between L-PC and u-PA ( Figure 4 ) interaction. Urokinase-type plasminogen activator (u-PA) was used as the stationary phase, and L-PC concentration gradients of 12.5M, 25μM, 50μM, 100μM and 200μM were set as the mobile phase for binding detection. The results are shown in Figure 6 As shown by Figure 6 It can be seen that with the increase of L-PC concentration, the increase of RU is more significant, showing a high binding affinity. The equilibrium dissociation constant (KD) value of the interaction between L-PC and u-PA is 2.32×10 -9 , further confirming the strong interaction between the two.

[0074] 5. Hemolytic activity detection

[0075] After obtaining blood samples from the First Affiliated Hospital of Kunming Medical University, they were immediately centrifuged at 3500 rpm and 25°C for 10 min to separate red blood cells. The supernatant was removed and the red blood cells were resuspended in PBS (0.01 M, pH 7.2) to adjust the concentration to 1 × 10 8 cells / mL. The adjusted red blood cells were incubated with the positive control 0.1% Triton X-100 and different concentrations of L-PC (0, 14.38, 28.75, 57.5, 115, 230 μg / ml) at 37°C for 30 min. After incubation, centrifuge at 3500 rpm and 37°C for 5 min, and the supernatant was collected. The absorbance was measured at a wavelength of 540 nm using a Gen5 microplate reader (Epoch, Bio-Tech, USA) to evaluate the effect of L-PC on hemolysis. The results are shown in Figure 7 As shown, from the changes in absorbance of each group detected at OD 450nm, it can be seen that the hemolytic activity of L-PC is not obvious compared with the positive control (TritonX-100).

[0076] 6. Cytotoxicity Assay

[0077] The toxicity of L-PC to primary human embryonic kidney 293T cells (HEK293T cells) was evaluated. HEK293T cells were cultured in DMEM / F-12 medium containing 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin solution, and then transferred to RPMI1640 complete medium and grown at 37°C and 5% CO2. The cytotoxicity of L-PC was analyzed using the CCK-8 kit. 3×10 4 HEK 293T cells / well were seeded in a 96-well plate. After culturing for 12 hours, the cells were treated with different concentrations of L-PC (0, 7.19, 14.38, 28.75, 57.5, 115, 230 μM; 0 μM L-PC was recorded as NC) and 10% dimethyl sulfoxide (DMSO) for 10 hours. 10 μL CCK-8 reagent was added to each well and incubated for another 3 hours. Finally, the absorbance was measured at a wavelength of 450 nm using an ELISA reader (Epoch 109 BioTek, USA), and the cell viability was expressed as a percentage relative to the control group. The results are shown in Figure 2. Figure 8 As shown, from the changes in absorbance of each group detected at OD 450nm, it can be seen that compared with the NC group, 7.19, 14.38, and 28.75 μM L-PC had no inhibitory effect on the survival rate of Hek-293T cells, and high concentrations of L-PC had a certain inhibitory effect on the survival rate of Hek-293T cells.

[0078] 7. Cortical Photothrombosis-Stroke (CPS) Mouse Model

[0079] In this experiment, male C57BL / 6J mice (6 weeks old, n=6-7 per group) were used to establish a cortical photothrombosis-stroke (CPS) model. One hour before the experiment, mice were intraperitoneally injected with 100 μl of Rose Bengal reagent (50 mg / kg). 5 minutes before the operation, 0.9% saline (control), 2500 U / kg heparin sodium (positive control group) and different doses of L-PC (1, 4.0 mg / kg) were injected through the tail vein, as well as a sham operation group (sham) in which the cortical photothrombosis model was not established. After anesthesia, an incision was made along the midline of the cerebral cortex to the neck to expose the skull. A 15mw 562nm yellow-green laser (R-LG561-100-A5, RWD, China) was used to irradiate the target area for 7 minutes. 24 hours after the operation, the mice were imaged with laser speckle perfusion (LSP) to record blood flow changes. By Fig. 9It can be seen that severe thrombosis and brain tissue damage occurred on the first day of photochemically induced thrombosis, which may be due to the fact that brain inflammation and subsequent activation of the coagulation cascade hindered the repair of intracranial injury, but L-PC and sodium heparin alleviated these effects and accelerated blood flow recovery on the fourth day. L-PC showed a positive effect in reducing thrombosis and the progression of thrombosis.

[0080] 8. Mouse tail bleeding experiment

[0081] Ten minutes before the experiment, 6-week-old male C57BL / 6J mice were given [2] (n=6-7 per group) were injected with different doses of L-PC (261.6, 784.8 μg / kg), 0.9% saline (NC group) and heparin sodium (2500 U / kg). The tail tip of the mice was cut off by 2 mm and immersed in sterile saline at 37°C. During the experiment, the bleeding time was carefully recorded until the bleeding stopped completely. The results are shown in Fig.10 As shown, 261.6 and 784.8 μg / kg did not affect the tail bleeding time of mice, but the 2500 U / kg heparin group prolonged the bleeding time, indicating that L-PC has a low bleeding risk potential.

[0082] 9. Evaluation of Intracerebral Hemorrhage Model

[0083] Eight-week-old C57BL / 6J mice (20-25 g, male) were selected, with 6 mice in each group, to establish a mouse cerebral hemorrhage model. [3] , 10 minutes before the establishment of the cerebral hemorrhage model, mice were injected into the tail vein and divided into: sham operation group (Shame), control group (C, saline group), heparin sodium group (2500U / kg, Heparin sodium) and different concentrations of L-PC groups (1 and 4mg / kg, 1mg / kg was marked as L1, 4mg / kg was marked as L4). Neurobehavioral scores were performed on mice 24 hours after the model was established. Then, the mice were killed by injection of overdose anesthesia, blood and brain were taken from the eyeballs, the brain was cut into 2mm thick coronal slices, and photos were taken to record the cerebral hemorrhage. The determination of brain water content was completed by measuring the wet weight of the left and right hemispheres of the brain and the dry weight after drying in a 65℃ oven for 48 hours. The calculation formula was: (wet weight-dry weight) / wet weight×100%. The hematoma area was determined by analyzing the hematoma area in the brain slices with ImageJ software, and the hemoglobin content in the cerebral hemorrhage site was determined by a hemoglobin ELISA kit. These experiments comprehensively evaluated the potential effects of L-PC on the bleeding risk in a mouse ICH model. Fig.11 As shown by Fig.11It can be seen that the risk of brain hemorrhage in mice injected with L-PC at concentrations of 1 mg / kg and 4 mg / kg respectively by tail vein injection was lower than that in the heparin group.

[0084] 10. Detection of the effect of L-PC on the inflammatory response of cerebral ischemia-reperfusion injury based on ischemia-reperfusion BBB chip

[0085] The ischemia-reperfusion BBB chip was constructed by performing oxygen glucose deprivation (OGD) treatment on the BBB chip to simulate the pathological conditions of ischemic stroke. After 24 hours of OGD treatment, normal perfusion, nutrition conditions and normoxic culture conditions were restored to simulate the occurrence of reperfusion after stroke. The purpose was to explore the possible aggravation of damage under reperfusion conditions. [4] In contrast, the tMCAO model is similar to the one in which recanalization occurs and drug treatment is performed during the perfusion phase to test the potential therapeutic effect of L-PC drugs on ischemic stroke.

[0086] Experimental Grouping

[0087] Con. (control group): samples without any treatment, serving as baseline control.

[0088] OGD (oxygen glucose deprivation group): Oxygen glucose deprivation treatment was performed to simulate the pathological conditions of ischemic stroke.

[0089] OGD-RE (oxygen glucose deprivation-reperfusion group): After 24 hours of OGD treatment, normal perfusion, nutritional conditions and normoxic culture conditions were restored to simulate reperfusion after stroke.

[0090] L-PC (20 μM): L-PC at a concentration of 20 μM was added to the endothelial channel (vascular side) before reperfusion simulation.

[0091] L-PC (50 μM): L-PC drug at a concentration of 50 μM was added to the endothelial channel (vascular side) before reperfusion simulation.

[0092] L-PC (100 μM): L-PC drug at a concentration of 100 μM was added to the endothelial channel (vascular side) before reperfusion simulation.

[0093] The experimental results are as follows:

[0094] The effects of different treatments on ischemia-reperfusion injury were evaluated by measuring the relative expression levels of cytokines (IL-1β and IL-6) in the two groups.

[0095] Results of IL-1β ( Fig.12 Center left picture):

[0096] The IL-1β expression level in the Con. group was the lowest; the IL-1β expression level in the OGD group increased slightly; the IL-1β expression level in the OGD-RE group increased significantly, indicating that reperfusion may have aggravated the injury; the IL-1β expression levels in the L-PC (20μM) and L-PC (50μM) groups were lower than those in the OGD-RE group, showing the potential effect of L-PC drugs in alleviating injuries; the IL-1β expression level in the L-PC (100μM) group was the lowest, indicating that L-PC drugs at a concentration of 100μM may have the best therapeutic effect.

[0097] Results of IL-6 ( Fig.12 Middle right picture):

[0098] The IL-6 expression level in the Con. group was the lowest; the IL-6 expression level in the OGD group increased slightly; the IL-6 expression level in the OGD-RE group increased significantly, further confirming that reperfusion may aggravate the injury; the IL-6 expression levels in the L-PC (20μM) and L-PC (50μM) groups were lower than those in the OGD-RE group, showing the potential effect of L-PC drugs in alleviating injuries; the IL-6 expression level in the L-PC (100μM) group was similar to that in the L-PC (50μM) group, indicating that at this concentration, the effect of the L-PC drug may have reached saturation.

[0099] The experimental results showed that L-PC drugs have potential therapeutic effects in alleviating the damage caused by ischemia-reperfusion during the reperfusion phase, especially at higher concentrations (such as 100 μM).

[0100] References

[0101] [1]LEE JK, PARK MS, KIM YS, et al.Photochemically induced cerebralischemia in amousemodel[J].SurgicalNeurology, 2007, 67(6):620-5.

[0102] [2]TANG

[0103] [3]CHEN CJ, DING D, IRONSIDE N, et al.Statins for neuroprotection inspontaneous intracerebralhemorrhage[J]. Neurology, 2019, 93(24):1056-1066.

[0104] [4] LYUZ, PARKJ, KIM KM, et al. Aneurovascular-unit-on-a-chip forthee evaluation of the restorative potential of stem cell therapies for ischaemicstroke [J]. Nature Biomedical Engineering, 2021, 5(8): 847-863.

[0105] Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

Claims

1. Use of L-palmitoylcarnitine in the preparation of antithrombotic drugs and / or anti-inflammatory drugs, wherein the chemical structural formula of the L-palmitoylcarnitine is shown in Formula I; 2. The use according to claim 1, characterized in that: The anti-thrombotic effect includes preventing, treating or alleviating thrombotic diseases; the anti-inflammatory effect includes alleviating the inflammatory response caused by ischemia-reperfusion.

3. The use according to claim 2, characterized in that: The thrombotic disease includes at least one of venous thrombosis, cerebral infarction and acute myocardial infarction.

4. The use according to claim 1, characterized in that: The thrombus includes arterial thrombus and / or venous thrombus.

5. The use according to claim 4, characterized in that: The venous thrombosis includes cortical vein thrombosis.

6. The use according to claim 5, characterized in that: The cortical vein thrombosis includes photochemically induced cortical vein thrombosis.

7. The use according to claim 1, characterized in that: The dosage form of the drug includes oral preparations or injections.

8. Use of L-palmitoylcarnitine in preparing an enhancer for urokinase-type plasminogen activator, wherein the chemical structural formula of the L-palmitoylcarnitine is shown in Formula I.

9. Use of L-palmitoyl carnitine in preparing products for maintaining vascular health, wherein the chemical structural formula of the L-palmitoyl carnitine is shown in Formula I.

10. The use according to claim 9, characterized in that: The maintenance of blood vessel health is achieved by anti-coagulation; the product includes food, health care products, nutritional supplements or medicines.

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