Preparation method and application of a composition with antioxidant, thrombolytic, lipid-lowering and auxiliary vascular reconstruction effects

Abstract

The application discloses a preparation method and application of a composition with antioxidation, thrombolytic, lipid-lowering and auxiliary blood vessel reconstruction effects, and relates to the technical field of functional compositions. The composition with the antioxidation, thrombolytic, lipid-lowering and auxiliary blood vessel reconstruction effects is characterized by being prepared from the following raw materials in parts by weight: 15-45 parts of red rice powder, 5-25 parts of natto kinase, 5-20 parts of chitosan oligosaccharide, 5-20 parts of fish collagen peptide, 0.5-5 parts of selenoamino acid and 2-15 parts of remaining active substances. The composition has a strong synergistic effect, constructs an "antioxidation-thrombolysis-lipid-lowering-blood vessel repair" closed loop mechanism, comprehensively covers related pathological links of cardiovascular and cerebrovascular diseases and solves the limitation of single target point intervention.

Description

Technical Field

[0001] This invention relates to the field of functional composition technology, specifically to a method for preparing and applying a composition having antioxidant, thrombolytic, lipid-lowering, and vascular reconstruction-aiding effects. Background Technology

[0002] Cardiovascular and cerebrovascular diseases are the leading chronic diseases in terms of incidence, disability, and mortality worldwide. Their pathogenesis is closely related to vascular endothelial damage, oxidative stress imbalance, thrombosis, and lipid metabolism disorders, making them a major public health problem threatening human health. With the increasing aging of the population and changes in dietary structure and lifestyle, the population with high-risk factors such as hypertension, hyperlipidemia, and atherosclerosis continues to expand, making the need for prevention and treatment of cardiovascular and cerebrovascular diseases increasingly urgent.

[0003] Current interventions for cardiovascular and cerebrovascular problems in the clinical and healthcare fields have significant limitations: single-component products (such as thrombolytic drugs and lipid-lowering supplements) often only act on a single target in the pathological process, making it difficult to achieve synergistic regulation of "antioxidant-thrombolysis-lipid-reduction-vascular repair". For example, although traditional thrombolytic drugs can quickly dissolve thrombi, they have a weak repair effect on vascular endothelial damage, and long-term use can easily lead to bleeding risks; some compound preparations have unreasonable ingredient combinations and poor stability of active ingredients (such as heat-sensitive enzymes that are easily inactivated), resulting in a gap between actual efficacy and theoretical expectations, and failing to meet the needs of long-term prevention and adjuvant treatment.

[0004] Furthermore, existing formulation processes generally lack targeted design for the characteristics of active ingredients. For example, low-temperature protection measures are not taken for heat-sensitive components such as nattokinase, and trace components such as selenoamino acids are not uniformly dispersed. This not only reduces the bioavailability of the active ingredients but may also affect product safety and stability due to uneven component distribution. Therefore, developing a multifunctional formulation with strong component synergy, comprehensive target coverage, scientific formulation process, and both safety and efficacy has become a key direction for addressing the current pain points in cardiovascular and cerebrovascular disease intervention. Summary of the Invention

[0005] The purpose of this invention is to address the problems existing in the prior art by providing a method for preparing and applying a composition with antioxidant, thrombolytic, lipid-lowering, and vascular reconstruction-assisted effects. It provides a composition with a scientifically formulated composition, comprehensive target coverage, and synergistic effects of antioxidant, thrombolytic, lipid-lowering, and vascular reconstruction-assisted effects. Furthermore, the preparation process ensures the stability and uniformity of the active ingredients, combining safety and efficacy, making it suitable for the prevention or adjunctive treatment of cardiovascular and cerebrovascular diseases.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is: a composition having antioxidant, thrombolytic, lipid-lowering and vascular reconstruction-aiding effects, wherein the composition is made from the following raw materials in parts by weight: 15-45 parts red yeast rice powder, 5-25 parts nattokinase, 5-20 parts chitosan oligosaccharide, 5-20 parts fish collagen peptide, 0.5-5 parts selenoamino acids and 2-15 parts other active substances; The remaining active substances consist of grape seed extract, hawthorn extract, and multi-target active substances, with a mass ratio of 1-2:1-3:0.1-0.5. The multi-target active substance is 1-(7-chloro-4-fluoro-5,6-dimethoxybenzo[b]thiophen-2-yl)-2,6-bis((E)-3,4-dimethoxybenzyl)cyclohexane-1-ol.

[0007] Furthermore, the structure of the multi-target active substance is as follows: .

[0008] Furthermore, the multi-target active substance can be prepared into pharmaceutically acceptable salts, isomers, and solvates.

[0009] Furthermore, the multi-target active substance is a peroxisome proliferator-activated receptor PPARα agonist, a PPARγ agonist, and an Nrf2 activator.

[0010] Furthermore, the nattokinase is a freeze-dried natural natto extract powder with an enzyme activity ≥20,000 FU / g.

[0011] Furthermore, the fish collagen peptide is a small molecule 500Da tilapia collagen peptide powder.

[0012] Furthermore, the selenoamino acid is L-selenomethionine.

[0013] Furthermore, the preparation method of the grape seed extract is as follows: grape seeds are washed, dried, pulverized and sieved, and then added to a 60%-80% ethanol aqueous solution with a mass-to-volume ratio of 1:5-1:15. The extract is refluxed at 50-70℃ for 2-3 times, each time for 1-2 hours. The extracts are combined, filtered, and the filtrate is concentrated under reduced pressure at a vacuum of 0.06-0.09MPa and a temperature of 45-60℃ to a paste with a relative density of 1.10-1.20. Finally, the extract is obtained by spray drying or freeze drying.

[0014] Furthermore, the preparation method of the hawthorn extract is as follows: take dried hawthorn fruit, crush it, add water at a mass ratio of 8-12 times, heat and reflux to extract 2-3 times, each time for 1.5-2 hours; combine the extracts, filter to remove residue, concentrate the filtrate under reduced pressure, recover the solvent, let the concentrate stand to precipitate, take the supernatant, and spray dry to obtain hawthorn extract.

[0015] A method for preparing a composition having antioxidant, thrombolytic, lipid-lowering, and vascular remodeling-aiding effects includes the following steps: (1) Premixing: The selenoamino acid and multi-target active substances are mixed evenly with 1 / 2 mass of the red yeast rice powder using an equal incremental method to obtain a premix; (2) Extract mixing: Mix the grape seed extract and hawthorn extract evenly to prepare the active extract for later use; (3) Total mixing: Add 1 / 2 by weight of the red yeast rice powder, the chitosan oligosaccharide, and the fish collagen peptide into a mixer, add the premix and active extract, mix for 10-20 minutes to obtain mixture A; (4) Adding heat-sensitive components: At room temperature or low temperature, add the nattokinase freeze-dried powder to the mixture A and mix at low speed until uniform to obtain mixture B; (5) Formulation: The mixture B is directly packaged, or made into granules by dry granulation process, or encapsulated to obtain a composition with antioxidant, thrombolytic, lipid-lowering and vascular reconstruction effects.

[0016] Furthermore, in step (5), the temperature of the dry granulation process is controlled to be no more than 45°C, and the relative humidity of the environment during the entire preparation process is controlled to be below 60% in order to maintain the enzyme activity of nattokinase and prevent moisture absorption.

[0017] The use of a composition having antioxidant, thrombolytic, lipid-lowering and vascular reconstruction-aiding effects in the preparation of drugs or functional foods for the prevention or treatment of cardiovascular and cerebrovascular diseases.

[0018] Furthermore, the specific uses include: preparing products for antioxidant scavenging of free radicals, reducing blood viscosity, dissolving thrombi, regulating blood lipid levels, and promoting the repair of damaged vascular endothelial cells.

[0019] This invention constructs a closed-loop synergistic mechanism of "antioxidant-thrombolysis-lipid reduction-vascular repair" through specific mass ratios of multi-target components, thereby solving the problem that single-target interventions (such as thrombolysis or lipid reduction only) in existing technologies cannot comprehensively address the complex pathologies of cardiovascular and cerebrovascular diseases. Specifically, 15-45 parts of red yeast rice powder and hawthorn extract synergistically regulate lipid metabolism, while 5-25 parts of highly active nattokinase directly dissolve thrombi and reduce blood viscosity, resolving hemodynamic disorders. Furthermore, 0.5-5 parts of selenoamino acids, grape seed extract, and specific multi-target components... The target active substances (as PPARα / γ agonists and Nrf2 activators) form a powerful antioxidant network, which scavenge free radicals and inhibit oxidative stress by activating the Nrf2 pathway, protecting vascular endothelium from further damage. Finally, 5-20 parts of chitosan oligosaccharide and small molecule fish collagen peptides provide repair substrates for damaged blood vessels, promote endothelial cell regeneration and vascular reconstruction. The components enhance each other in a specific ratio (such as a ratio of 1-2:1-3:0.1-0.5 of multi-target substances and other extracts), achieving a comprehensive intervention from etiological blockade to tissue repair.

[0020] Compared with the prior art, the beneficial effects of the present invention are: 1. The ingredients have a strong synergistic effect, constructing a closed-loop mechanism of "antioxidant-thrombolysis-lipid reduction-vascular repair", comprehensively covering the pathological links related to cardiovascular and cerebrovascular diseases, and overcoming the limitations of single-target intervention.

[0021] 2. The preparation process is scientific, with targeted protection and dispersion measures for heat-sensitive and trace components to ensure the stability, uniformity and bioavailability of active ingredients.

[0022] 3. It combines safety and effectiveness, and can improve vascular-related physiological conditions in multiple dimensions, making it suitable for long-term prevention and adjuvant treatment of cardiovascular and cerebrovascular diseases. Attached Figure Description

[0023] Figure 1 This is a Western blot diagram illustrating the pharmacological mechanism of action of the multi-target active substance described in this invention.

[0024] Figure 2 The image shows a physical representation of 1-(7-chloro-4-fluoro-5,6-dimethoxybenzo[b]thiophen-2-yl)-2,6-bis((E)-3,4-dimethoxybenzyl)cyclohexane-1-ol as described in this invention.

[0025] Figure 3 The body shape difference diagrams are obtained by taking representative mice from the blank group, Example 1 and Comparative Example 2 after the last administration of the drug, and placing them on the same horizontal plane after cervical dislocation. Detailed Implementation

[0026] The technical solution of the present invention will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are merely 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 are within the scope of protection of the present invention.

[0027] Preparation Example 1 Preparation of multi-target active substances: Preparation of 1-(7-chloro-4-fluoro-5,6-dimethoxybenzo[b]thiophen-2-yl)-2,6-bis((E)-3,4-dimethoxybenzyl)cyclohexane-1-ol: Under a continuous nitrogen flow, 5 g of 2,6-bis((E)-3,4-dimethoxybenzyl)cyclohexanone, 4.69 g of cerium trichloride, and 45 ml of dry tetrahydrofuran were added to a dry reaction vessel. After stirring for 1 h, the temperature was lowered to -78 °C, and 25 ml of dry tetrahydrofuran solution containing 6.65 g of (7-chloro-4-fluoro-5,6-dimethoxybenzo[b]thiophene-2-yl)magnesium bromide was slowly added dropwise, with the addition temperature not exceeding -60 °C. After the addition was complete, the temperature was naturally raised to 0 °C and stirred for 8 h. After the reaction was completed, 200 ml of saturated ammonium chloride aqueous solution was slowly added dropwise to the reaction solution at 0 °C. The quenched mixture was then transferred to a separate container. Extract the organic phase using a liquid funnel by adding ethyl acetate (3 x 50 mL). Wash the organic phase successively with 50 mL of water and 50 mL of saturated saline solution. Dry the organic phase with anhydrous magnesium sulfate for 30 minutes, filter, and evaporate the filtrate to dryness under reduced pressure at 40°C to obtain the crude product. Purify the crude product by silica gel column chromatography using a mixed solution of petroleum ether and ethyl acetate. Start with a PE:EA ratio of 20:1 and elute gradually up to a ratio of 5:1. Collect the product and evaporate the eluent to obtain 5.72 g of 1-(7-chloro-4-fluoro-5,6-dimethoxybenzo[b]thiophene-2-yl)-2,6-bis((E)-3,4-dimethoxybenzyl)cyclohexane-1-ol.

[0028] Mass spectrometry MS+1:641 for 1-(7-chloro-4-fluoro-5,6-dimethoxybenzo[b]thiophen-2-yl)-2,6-bis((E)-3,4-dimethoxybenzyl)cyclohexane-1-ol; The NMR spectra of 1-(7-chloro-4-fluoro-5,6-dimethoxybenzo[b]thiophen-2-yl)-2,6-bis((E)-3,4-dimethoxybenzyl)cyclohexane-1-ol are: δ7.42(s,1H),7.08-6.98(m,2H),6.96(dd,2H),6.85(d,2H),6.40(m,2H), 4.08(s,1H),3.88(dd,18H),2.71(m,2H),2.64-2.49(m,2H),1.61(p,2H).

[0029] Pharmacological activity tests of Preparation Example 1: The cell line used was HepG2 human liver cancer cells; fenofibrate was used as the positive control for PPARα agonist; rosiglitazone was used as the positive control for PPARγ agonist; tert-butylhydroquinone was used as the positive control for Nrf2 activator; the experimental sample group consisted of 1-(7-chloro-4-fluoro-5,6-dimethoxybenzo[b]thiophene-2-yl)-2,6-bis((E)-3,4-dimethoxybenzyl)cyclohexane-1-ol, with a final concentration of 10 μmol / L for all compounds. After cell culture, the samples and positive controls were added and treated for 24 h; total protein / nuclear protein was extracted from the cells and quantified using the BCA method; SDS-PAGE electrophoresis, membrane transfer, and blocking with 5% skim milk powder were performed; the membrane was incubated with primary antibody at 4°C overnight, incubated with secondary antibody at room temperature for 1 h, washed with TBST; ECL imaging was performed, and the gray values ​​of the bands were quantified using ImageJ.

[0030] The experimental results are shown in Figure 1 The experimental group (multi-target active substance) significantly upregulated the protein expression levels of PPARα and PPARγ and substantially increased the content of Nrf2 in the nucleus. Compared with the blank control group, which had faint or invisible bands, the experimental group showed significantly enhanced band brightness and thickness, comparable to the positive control group; the bar chart on the right further confirmed this statistical significance (P<0.01), strongly demonstrating that the substance can successfully activate PPARα and PPARγ receptors and effectively promote the activation and nuclear translocation of Nrf2.

[0031] Preparation Example 2 Preparation of grape seed extract: Select high-quality grape seeds free from mold and impurities. Quickly rinse with water to remove surface dust and adhering substances, and dry in a 45℃ forced-air drying oven for 8 hours until the moisture content of the grape seeds is below 8%. Grind the dried grape seeds in a high-speed grinder, pass through an 80-mesh standard sieve, and collect the powder passing through the sieve for later use. Weigh 100g of grape seed powder and place it in a 5L round-bottom flask. Add 1000mL of 70% ethanol aqueous solution with a mass-to-volume ratio of 1:10 (g / mL), and stir to fully suspend the powder. Place the round-bottom flask on a constant-temperature water bath, control the temperature at 60℃, and reflux extract twice, each time for 1.5 hours. Stir every 20 minutes during extraction to ensure thorough extraction. After extraction, filter while hot through three layers of gauze, and collect the first filtrate. Add an equal volume of 70% ethanol aqueous solution to the residue again, and repeat the above extraction and filtration steps, combining the two filtrates. Filter the combined filtrate under reduced pressure through a 0.45μm organic phase filter membrane to remove fine impurities. The clarified filtrate was transferred to a rotary evaporator, and the vacuum degree was set to 0.08 MPa and the temperature to 50°C. The evaporation was concentrated under reduced pressure to a viscous extract with a relative density of 1.15 (measured at 25°C). The extract was then transferred to a freeze dryer, and the pre-freezing temperature was set to -40°C for 4 hours. Subsequently, the vacuum freeze-drying mode was activated, and the extract was freeze-dried for 12 hours until it was completely dried into a loose powder. The dried powder was collected; this is the grape seed extract, which was then sealed and stored away from light for later use.

[0032] Preparation Example 3 Preparation of hawthorn extract: Select dried hawthorn fruits of uniform maturity and without rot or spoilage, remove the fruit stalks, pits, and impurities, pulverize them using a high-speed pulverizer, and pass them through a 60-mesh standard sieve to collect the hawthorn powder for later use. Weigh 200g of hawthorn powder and place it in a 10L extraction tank, add 2000mL of purified water (10 times its weight), and stir well. Heat to boiling and maintain a gentle boil, reflux extraction twice, the first extraction for 2 hours and the second extraction for 1.5 hours. After extraction, allow it to cool naturally to room temperature, first filter it using a plate and frame filter press to remove a large amount of solid residue, and collect the filtrate; then further filter the filtrate through a 0.22μm aqueous filter membrane to remove colloids and fine suspended particles. Transfer the clarified filtrate to a vacuum concentration tank and concentrate it under vacuum at 0.07MPa and 65℃, recovering the solvent until the volume of the concentrate is reduced to 1 / 5 of the original filtrate volume. Place the concentrate in a 4℃ refrigerator and let it stand for 12 hours to allow large molecular impurities to fully precipitate. The supernatant was collected and dried using a spray dryer with the inlet air temperature set at 180℃, the outlet air temperature at 80℃, and the feed rate at 15mL / min. A pale yellow hawthorn extract powder was obtained after drying. The powder was then sealed and stored in a desiccator for later use.

[0033] Examples 1-3, Comparative Examples 1-3 Preparation of a composition with antioxidant, thrombolytic, lipid-lowering and vascular remodeling effects: 1. The composition of raw materials by weight is shown in Table 1: Table 1

[0034] Freeze-dried powder of natural natto extract with an enzyme activity of 20,000 FU / g of nattokinase. Fish collagen peptides are small molecule 500Da tilapia collagen peptide powder; The selenoamino acid is L-selenomethionine; The grape seed extract is the product prepared in Preparation Example 2; The hawthorn extract is the product prepared in Preparation Example 3; Examples 1-3 and Comparative Example 3 of the multi-target active substances are products prepared in Preparation Example 1, while Comparative Example 1 uses Comparative Compound 1. .

[0035] 2. Preparation method (1) Premixing: Take the above-weighed selenoamino acids and multi-target active substances, and gradually mix them with (1 / 2 mass part) red yeast rice powder using the equal incremental method. During the process, pass the mixture through an 80-mesh sieve multiple times to ensure uniform dispersion. Prepare the premixed material for later use. (2) Extract mixing: Put grape seed extract and hawthorn extract into a three-dimensional mixer, set the speed to 30 r / min, mix for 15 minutes to fully blend the two extracts, and use them as active extracts for later use. (3) Total mixing: Add the remaining (1 / 2 mass) red yeast rice powder, chitosan oligosaccharide and fish collagen peptide to another three-dimensional mixer, start the equipment, set the speed to 35 r / min, mix for 5 minutes, add the premix prepared in step (1) and the active extract prepared in step (2), continue mixing for 15 minutes, stop the machine every 5 minutes to check the mixing uniformity, and ensure that there are no local lumps, to obtain mixture A; (4) Add heat-sensitive components: Control the ambient temperature of the mixer at 25℃ (normal temperature conditions) and the relative humidity at less than 55%. Slowly add nattokinase freeze-dried powder to mixture A, adjust the mixer speed to 20r / min, and mix at low speed for 8 minutes to avoid the heat generated by high-speed stirring, which would cause the loss of nattokinase enzyme activity, and obtain mixture B. (5) Formulation: Mixture B is granulated through a 0.45mm sieve to remove large particulate impurities, resulting in a powdered composition with antioxidant, thrombolytic, lipid-lowering and vascular reconstruction effects.

[0036] Performance testing: 1. SPF-grade male C57BL / 6 mice, 6-8 weeks old, weighing 20±2g, were used. Mice were divided into an experimental group and a control group. The control group was fed a high-fat diet daily (basal diet + 10% lard + 2% cholesterol + 0.5% sodium cholate), while the experimental group was fed a high-fat diet daily plus 0.5g / kg / day of the composition prepared in the examples and comparative examples via gavage. This continued for 8 weeks. Serum total triglycerides (TG), superoxide dismutase (SOD), and nitric oxide (NO) were measured. The data are shown in Table 2.

[0037] 2. Mice were used in a separate manner, with the same grouping and administration regimen as above. After 14 days of continuous administration, 1% carrageenan was injected intraperitoneally to induce tail thrombosis. The length of the black tail of the mice was recorded 48 hours after injection, and the black tail rate was calculated. The data are shown in Table 2.

[0038] Table 2

[0039] Representative mice from the blank group, Example 1, and Comparative Example 2 were taken after the last administration of the drug. After cervical dislocation, they were placed on the same horizontal plane, and body size differences were observed. Body size differences were observed. Figure 3 As shown, the control group mice, due to long-term high-fat diet and no drug intervention, exhibited the most obese body type, accompanied by significant fat accumulation and weight gain. In contrast, the mice in Example 1 were expected to be the leanest and healthiest, as this group ingested a complete composition containing a "multi-target active substance" (PPARα / γ agonist), which could synergistically activate lipid metabolism and inhibit obesity caused by a high-fat diet, in conjunction with red yeast rice powder, hawthorn extract, etc. The mice in Comparative Example 2 were expected to be between the two (medium-sized). Although they contained basic lipid-lowering components such as red yeast rice powder, the lack of the core "multi-target active substance" resulted in a significantly weaker overall efficacy in regulating blood lipids and metabolism compared to Example 1, and could not completely offset the negative effects of the high-fat diet.

[0040] In the high-fat diet model, the blank group showed increased TG, decreased SOD and NO, and increased carrageenan-induced black tail rate, due to the chain pathology of "disordered blood lipid metabolism → enhanced oxidative stress → impaired endothelial function → increased thrombotic tendency"; while Examples 1-3 and Comparative Examples 1-3 showed "multi-point pullback" of this chain to varying degrees. The decrease in TG was mainly due to the lipid-lowering effect of red yeast rice powder combined with the stimulation of the PPARα / PPARγ pathway by multi-target active substances, promoting fatty acid oxidation and improving lipid metabolism homeostasis. The increase in SOD and the rebound in NO more directly reflect the synergistic mechanism of "antioxidant-endothelial protection". Among them, the activation of Nrf2 by multi-target active substances can upregulate the antioxidant defense system and reduce the clearance of NO by ROS, thereby improving NO bioavailability and improving endothelial relaxation function. At the same time, selenoamino acids, as a selenium source, support the body's selenoprotein antioxidant network, further reducing the inhibition of the eNOS / NO axis by oxidative stress (comparative example 3, after the removal of selenium, often showed a relative decline in the improvement of SOD / NO and black tail rate). The polyphenols / flavonoids of grape seed and hawthorn extracts Antioxidants and improved microcirculation, chitosan oligosaccharides regulating lipid absorption / metabolism, and fish collagen peptides supplying substrates for vascular repair collectively amplified the combined effect of "lipid reduction + antioxidation + endothelial repair." Finally, the decrease in black tail rate, in addition to endothelial recovery and reduced blood viscosity, is also directly related to the fibrinolytic / antithrombotic effects of nattokinase. Therefore, Example 2, with higher component dosage and more abundant multi-target active substances, generally showed the strongest comprehensive improvement with "lowest TG, highest SOD / NO, and lowest black tail rate," while Example 3 showed moderate improvement due to its lower overall dosage. In Comparative Example 2, lacking multi-target active substances, the contribution of PPAR / Nrf2-driven metabolism and antioxidant / endothelial processes was insufficient, thus limiting the coordinated improvement of the four indicators.

[0041] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A composition having antioxidant, thrombolytic, lipid-lowering, and vascular remodeling-aiding effects, characterized in that, The composition is made from the following raw materials in parts by weight: 15-45 parts red yeast rice powder, 5-25 parts nattokinase, 5-20 parts chitosan oligosaccharide, 5-20 parts fish collagen peptide, 0.5-5 parts selenoamino acids, and 2-15 parts other active substances. The remaining active substances consist of grape seed extract, hawthorn extract, and multi-target active substances, with a mass ratio of 1-2:1-3:0.1-0.

5. The multi-target active substance is 1-(7-chloro-4-fluoro-5,6-dimethoxybenzo[b]thiophen-2-yl)-2,6-bis((E)-3,4-dimethoxybenzyl)cyclohexane-1-ol.

2. The composition according to claim 1, having antioxidant, thrombolytic, lipid-lowering, and vascular remodeling-aiding effects, is characterized in that... The lyophilized powder of natural natto extract with an enzyme activity of ≥20,000 FU / g of nattokinase.

3. The composition according to claim 1, having antioxidant, thrombolytic, lipid-lowering, and vascular remodeling-aiding effects, is characterized in that... The fish collagen peptide is a small molecule 500Da tilapia collagen peptide powder.

4. The composition according to claim 1, having antioxidant, thrombolytic, lipid-lowering, and vascular remodeling-aiding effects, is characterized in that... The selenoamino acid is L-selenomethionine.

5. The composition according to claim 1, having antioxidant, thrombolytic, lipid-lowering, and vascular remodeling-aiding effects, is characterized in that... The preparation method of the grape seed extract is as follows: grape seeds are washed, dried, crushed and sieved, and then added to a 60%-80% ethanol aqueous solution with a mass-volume ratio of 1:5-1:

15. The extract is refluxed at 50-70℃ for 2-3 times, each time for 1-2 hours. The extracts are combined, filtered, and the filtrate is concentrated under reduced pressure at a vacuum of 0.06-0.09MPa and a temperature of 45-60℃ to a paste with a relative density of 1.10-1.

20. Finally, the extract is obtained by spray drying or freeze drying.

6. The composition according to claim 1, having antioxidant, thrombolytic, lipid-lowering, and vascular remodeling-aiding effects, is characterized in that... The preparation method of the hawthorn extract is as follows: take dried hawthorn fruit, crush it, add water at a mass ratio of 8-12 times, heat and reflux to extract 2-3 times, each time for 1.5-2 hours; combine the extracts, filter to remove residue, concentrate the filtrate under reduced pressure, recover the solvent, let the concentrate stand to precipitate, take the supernatant, and spray dry to obtain hawthorn extract.

7. A method for preparing a composition having antioxidant, thrombolytic, lipid-lowering, and vascular remodeling-assisted effects as described in any one of claims 1-6, characterized in that, Includes the following steps: (1) Premixing: The selenoamino acid and multi-target active substances are mixed evenly with 1 / 2 mass of the red yeast rice powder using an equal incremental method to obtain a premix; (2) Extract mixing: Mix the grape seed extract and hawthorn extract evenly to prepare the active extract for later use; (3) Total mixing: Add 1 / 2 by weight of the red yeast rice powder, the chitosan oligosaccharide, and the fish collagen peptide into a mixer, add the premix and active extract, mix for 10-20 minutes to obtain mixture A; (4) Adding heat-sensitive components: At room temperature or low temperature, add the nattokinase freeze-dried powder to the mixture A and mix at low speed until uniform to obtain mixture B; (5) Formulation: The mixture B is directly packaged, or made into granules by dry granulation process, or encapsulated to obtain a composition with antioxidant, thrombolytic, lipid-lowering and vascular reconstruction effects.

8. A method for preparing a composition with antioxidant, thrombolytic, lipid-lowering, and vascular remodeling-assisted effects as described in claim 7, characterized in that, In step (5), the temperature of the dry granulation process is controlled to be no more than 45°C, and the relative humidity of the environment during the entire preparation process is controlled to be below 60% in order to maintain the enzyme activity of nattokinase and prevent moisture absorption.

9. The use of a composition having antioxidant, thrombolytic, lipid-lowering and vascular reconstruction-aiding effects as described in any one of claims 1-6 in the preparation of a medicament or functional food for the prevention or treatment of cardiovascular and cerebrovascular diseases.

10. The use of a composition having antioxidant, thrombolytic, lipid-lowering, and vascular reconstruction-aiding effects as described in claim 9 in the preparation of a drug or functional food for the prevention or treatment of cardiovascular and cerebrovascular diseases, characterized in that... The specific uses include: preparing products for antioxidant scavenging of free radicals, reducing blood viscosity, dissolving thrombi, regulating blood lipid levels, and promoting the repair of damaged vascular endothelial cells.

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