A hydrogen bond self-assembled salvianolic acid B-curcumin macrophage membrane-coated nano preparation and a preparation method and application thereof

Abstract

The application discloses a kind of based on hydrogen bond self-assembly's salvianolic acid B-curry macrophage membrane coating nano preparation and its preparation method, application, it is related to nanometer medicine preparation field, including salvianolic acid B-curry covalent conjugate self-assembly nanomicelle and the M2 type macrophage membrane that is coated on the surface of nanomicelle, wherein salvianolic acid B-curry covalent conjugate self-assembly nanomicelle is covalently bonded by salvianolic acid B and curry through ester bond and forms SC conjugate, SC conjugate is formed spherical nanomicelle by intermolecular hydrogen bond self-assembly, M2 type macrophage membrane is completely coated on the surface of nanomicelle to form the SCM nano preparation of core-shell structure;The preparation is constructed by covalent ester bond and hydrogen bond self-assembly biomimetic core-shell structure, realizes targeted slow release and synergistic effect.

Description

Technical Field

[0001] This invention relates to nanomedicine formulation technology, specifically to a hydrogen-bonded self-assembled salvianolic acid B-curcumin macrophage membrane-coated nanoformulation, its preparation method, and its application. Background Technology

[0002] Atherosclerosis is the core pathological basis of cardiovascular and cerebrovascular diseases such as coronary heart disease and stroke. Its occurrence and development involve multiple interconnected pathological processes, including endothelial damage, oxidative stress imbalance, inflammatory cell infiltration, lipid peroxidation and deposition, and foam cell formation. Comprehensive intervention targeting these multi-target pathological processes is an effective strategy for the prevention and treatment of atherosclerosis.

[0003] Tanshinone B and curcumin are two widely available and safe natural polyphenolic active ingredients. Modern pharmacological studies have confirmed that they both have significant antioxidant, anti-inflammatory, vascular endothelial protective, and foam cell inhibition effects, and can synergistically inhibit the progression of atherosclerosis at multiple key stages, making them highly promising candidate drugs for anti-atherosclerosis. However, both active ingredients have significant inherent defects in their drug-likeness: they have extremely poor water solubility, making them difficult to absorb by the gastrointestinal tract after oral administration; they are rapidly metabolized in vivo with short half-lives, and are easily cleared by the liver and intestinal enzymes; they lack the ability to actively target atherosclerotic plaques, and cannot effectively accumulate and maintain therapeutic concentrations at vascular lesions. These defects collectively result in extremely low oral bioavailability and poor efficacy as monotherapy, severely restricting their clinical translation and application.

[0004] To address the aforementioned issues, existing technologies attempt to physically mix salvianolic acid B with curcumin or co-encapsulate both within conventional nanocarriers such as liposomes and polymer nanoparticles. While these methods have improved drug solubility and in vivo circulation time to some extent, fundamental technical limitations remain:

[0005] Firstly, relying solely on physical encapsulation or mixing results in a lack of strong interactions between the drug and the carrier, as well as between the two drug molecules. This leads to a loose formulation structure, making it prone to premature drug leakage during storage and circulation, and failing to guarantee structural integrity during delivery.

[0006] Secondly, the conventional nanocarriers used lack the ability to specifically recognize and adhere to atherosclerotic plaques. Targeting of lesions mainly relies on enhancing the penetration and retention effect, resulting in low active targeting efficiency and difficulty in achieving precise drug delivery.

[0007] Third, such co-delivery systems typically lack the ability to release drugs in response to the pathological microenvironment (such as the acidic microenvironment of inflammatory lesions), and the drug release behavior is mostly passive diffusion, which cannot achieve on-demand long-lasting effects.

[0008] Fourth, the physical mixing method failed to fully stimulate the cascade synergistic effect of the two drug molecules in the antioxidant and anti-inflammatory signaling pathways, thus limiting the efficacy. The root cause of the above defects is that the existing technology has not yet established an integrated nanodelivery platform that can stably and orderly combine two drugs at the molecular level and integrate active targeting and intelligent response drug release functions.

[0009] Therefore, there is an urgent need in this field to develop an integrated drug delivery platform that can achieve stable binding and orderly assembly of two drug molecules at the molecular level, while integrating active targeting, microenvironment response, synergistic effect, and highly stable drug loading. This platform would overcome multiple obstacles in the delivery process of both salvianolic acid B and curcumin, achieving synergistic effect, active targeting, and controllable sustained release, thus providing efficient and safe candidate drugs for the prevention and treatment of atherosclerosis and related cardiovascular and cerebrovascular diseases. Summary of the Invention

[0010] The purpose of this invention is to provide a hydrogen-bonded self-assembled salvianolic acid B-curcumin macrophage membrane-coated nano-formulation, its preparation method, and its application, in order to solve the problems of unstable structure, lack of active plaque targeting ability, and lack of pH-responsive drug release characteristics in existing physical mixtures of salvianolic acid B and curcumin.

[0011] To achieve the above objectives, the present invention provides the following technical solution: a nano-formulation of salvianolic acid B-curcumin macrophage membrane based on hydrogen bond self-assembly, comprising salvianolic acid B-curcumin covalent conjugate self-assembled nanomicelles and an M2-type macrophage membrane coated on the surface of the nanomicelles, wherein salvianolic acid B and curcumin in the salvianolic acid B-curcumin covalent conjugate self-assembled nanomicelles are bonded by covalent ester bonds to form SC conjugates, and the SC conjugates are self-assembled by intermolecular hydrogen bonds to form spherical nanomicelles, and the M2-type macrophage membrane is completely coated on the surface of the nanomicelles to form a core-shell structured SCM nano-formulation.

[0012] Furthermore, the average particle size of the SC conjugate nanomicelles is 5-10 nm, the critical micelle concentration is 189 μg / mL, and the Zeta potential of the SCM nanoformulation is -10.13 ± 0.94 mV.

[0013] Furthermore, the encapsulation efficiency of curcumin was 95.82%, and the drug loading rate was 32.47%.

[0014] A method for preparing a hydrogen-bonded self-assembled nanoparticle of salvianolic acid β-curcumin macrophage membrane coating includes the following steps:

[0015] S1: Synthesis of salvianolic acid B-curcumin SC conjugate: 0.368 g curcumin was dissolved in 10 mL anhydrous DMSO, 0.41 g DCC and 0.24 g DMAP were added, and the carboxyl group was activated by stirring at room temperature for 30 min; 0.718 g salvianolic acid B was added, and the reaction was carried out at room temperature in the dark for 48 h; after filtering the reaction solution, diethyl ether was added to precipitate a dark orange precipitate, and the crude product was dialyzed through DMSO and ultrapure water in sequence, and freeze-dried to obtain a yellow powder SC conjugate;

[0016] S2: Extraction of M2 macrophage membrane: RAW264.7 mouse macrophages were cultured to the logarithmic growth phase, washed with PBS and the cells were collected; the cells were resuspended in pre-cooled TM buffer, incubated overnight in a hypotonic atmosphere at 4°C, and homogenized to disrupt the cells; the sucrose concentration was adjusted to 0.25M, and the cells were removed by gradient centrifugation. The precipitate was washed to obtain purified macrophage membranes, which were stored at low temperature for later use.

[0017] S3: Assembly of SCM nanoparticles: The purified M2 macrophage membrane was mixed evenly with the SC conjugate PBS solution, vortexed and incubated at 4°C for 12 h; the macrophage membrane-coated SCM nanoparticles were prepared by repeated extrusion through a 100 nm polycarbonate porous membrane.

[0018] Furthermore, the dialysis conditions in step S1 are: molecular weight cutoff of 500 Da, dialysis with DMSO for 2 days, and dialysis with ultrapure water for 3 days.

[0019] Furthermore, in step S2, the TM buffer consisted of 10 mM Tris + 1 mM MgCl2, pH 7.4; the cell resuspending density was 3.0 × 10⁻⁶ cells / mL. 7 The concentration of PMSF was 1% of the system volume.

[0020] Furthermore, the centrifugation parameters in step S2 are as follows: centrifuge at 4°C and 2000 rcf for 15 min to remove precipitate impurities, centrifuge at 3000 rcf for 30 min to collect cell membrane precipitate, and wash 3 times with ice™ buffer.

[0021] Furthermore, in step S3, the extrusion process uses a micro extruder for continuous extrusion to ensure complete cell membrane coverage and uniform particle dispersion.

[0022] The application of a hydrogen-bonded self-assembled salvianolic acid β-curcumin macrophage membrane-coated nanoparticle formulation in the preparation of drugs for the prevention, delay, or treatment of atherosclerosis and related cardiovascular and cerebrovascular diseases. The drug can be formulated as an oral or injectable preparation.

[0023] Compared with existing technologies, this invention provides a hydrogen-bonded self-assembly-based nano-formulation of salvianolic acid B-curcumin macrophage membrane-coated nanoparticles, its preparation method, and applications. On one hand, salvianolic acid B and curcumin are covalently linked by DCC / DMAP-catalyzed esterification to form an SC conjugate. The intermolecular hydrogen bonding forces drive the self-assembly of the conjugate to form a uniformly sized and structurally stable nanomicelle core, fundamentally overcoming the defects of loose structures and easy drug leakage in physically mixed formulations. On the other hand, the M2-type macrophage membrane is used to biomimeticly encapsulate the nanomicelles. By leveraging the natural recognition and adhesion capabilities of macrophage membrane surface proteins to the inflammatory microenvironment of atherosclerotic plaques and sites of vascular injury, the formulation possesses the function of actively targeting lesions. At the same time, it improves the biocompatibility and immune escape ability of the formulation, achieving synergistic antioxidant and anti-inflammatory effects of salvianolic acid B and curcumin at the plaque site. It effectively inhibits oxidative stress damage and inflammatory cascade reactions, protects vascular endothelial function, and provides a nano-drug delivery solution with structural stability, targeted delivery and controllable sustained release for the prevention and treatment of atherosclerosis and related cardiovascular and cerebrovascular diseases. Attached Figure Description

[0024] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in this invention. For those skilled in the art, other drawings can be obtained based on these drawings.

[0025] Figure 1 The above is the ¹H NMR spectrum of the SC conjugate in Example 2 of this invention.

[0026] Figure 2 The image shows the Fourier Transform Infrared (FTIR) spectrum of the SC conjugate in Example 2 of this invention.

[0027] Figure 3 The image shows the ultraviolet (UV) spectrum of the SC conjugate in Example 2 of this invention.

[0028] Figure 4 This is a transmission electron microscope (TEM) image of the self-assembled micelles of the SC conjugate in Example 2 of the present invention;

[0029] Figure 5 This is a graph showing the critical micelle concentration (CMC) determination of the SC conjugate in Example 2 of the present invention;

[0030] Figure 6 This is an in vitro drug release kinetic curve of SC micelles in Example 2 of the present invention;

[0031] Figure 7This is a comparison diagram of the DPPH free radical scavenging activities of the SC conjugate and free curcumin in Example 2 of the present invention;

[0032] Figure 8 This is the ultraviolet (UV) spectrum of the SCM nano-formulation in Example 2 of the present invention;

[0033] Figure 9 This is a comparison chart of the storage stability of SC micelles and SCM nano-formulations in Example 2 of the present invention. Detailed Implementation

[0034] To enable those skilled in the art to better understand the technical solution of the present invention, the present invention will be further described in detail below with reference to the accompanying drawings.

[0035] Example 1:

[0036] This invention provides a method for preparing a nano-formulation of salvianolic acid β-curcumin macrophage membrane-coated based on hydrogen bond self-assembly, the specific steps of which are as follows:

[0037] S1: Synthesis of the salvianolic acid B-curcumin SC conjugate: 0.368 g of curcumin was dissolved in 10 mL of anhydrous DMSO, and 0.41 g of DCC and 0.24 g of DMAP were added. The mixture was stirred at room temperature for 30 minutes to activate the carboxyl group. Subsequently, 0.718 g of salvianolic acid B was added, and the mixture was stirred at room temperature in the dark for 48 hours. After the reaction was completed, the mixture was filtered, and diethyl ether was added to the filtrate, resulting in a dark orange precipitate. The crude product was redissolved in DMSO, and dialyzed against DMSO for 2 days and ultrapure water for 3 days (molecular weight cutoff 500 Da). After freeze-drying, a yellow powdery SC conjugate was obtained.

[0038] S2: Extraction of M2 macrophage membranes: RAW264.7 mouse macrophages were seeded in DMEM high-glucose medium containing 10% fetal bovine serum and cultured at 37°C in a 5% CO2 incubator until the logarithmic growth phase. The medium was discarded, and the cells were washed twice with PBS buffer. Cells were scraped and collected into centrifuge tubes. The cells were resuspended in pre-chilled TM buffer (10 mM Tris, 1 mM MgCl2, pH 7.4) to a density of 3.0 × 10⁻⁶ cells / mL. 7 Cells were homogenized at 1% per mL with 1% PMSF and incubated overnight at 4°C under hypotonic conditions. Cell structure was disrupted by repeatedly squeezing the homogenate 30 times. The cell homogenate was mixed with 1M sucrose solution to a final sucrose concentration of 0.25M, and centrifuged at 4°C and 2000 rcf for 15 minutes. The precipitate was discarded to remove cell debris. The supernatant was collected and centrifuged at 4°C and 3000 rcf for 30 minutes. The precipitate was collected and washed three times with ice-cold™ buffer to obtain purified M2 macrophage membranes, which were stored at -80°C for later use.

[0039] S3: Assembly of SCM nanoparticles: Take an appropriate amount of the M2 macrophage membrane prepared in step S2, mix it evenly with the PBS solution of the SC conjugate prepared in step S1, vortex for 2 minutes, and incubate at 4°C for 12 hours. Use a micro extruder to continuously extrude the mixture through a 100nm polycarbonate porous membrane to obtain the SCM nanoparticles coated with M2 macrophage membranes.

[0040] Example 2: Structural Characterization and Performance Testing

[0041] The SC conjugate and SCM nanoformulation prepared in Example 1 above were subjected to the following structure and performance tests:

[0042] 1) ¹H NMR analysis: An appropriate amount of the SC conjugate was dissolved in deuterated DMSO and subjected to ¹H NMR analysis, with the raw materials salvianolic acid B and curcumin serving as controls. Results showed that the characteristic doublet of curcumin at δ2.73 ppm and δ2.83 ppm, belonging to the β-diketone methylene group (-CO-CH2-CO-), shifted to δ2.77 ppm and δ2.93 ppm in the product SC spectrum, indicating a significant change in the chemical environment of the active site due to the involvement of adjacent phenolic hydroxyl groups in bonding. The characteristic signals of salvianolic acid B at δ2.50 ppm and δ3.30 ppm (attributed to the methylene protons linked to the α-position of the carboxyl group and the ether bond, respectively) were retained in the SC spectrum, but their chemical shifts changed. A new signal peak, absent in the raw materials, appeared at δ3.05 ppm in the SC spectrum, corresponding to the proton at the newly formed ester bond connection point. The signal intensity in the aromatic region of δ6-8 ppm in the SC spectrum significantly decreased, further indicating molecular structural reorganization. The above signal shifts, the appearance of new peaks, and the non-additive changes in the spectrum collectively confirm that a covalent ester bond has been formed between salvianolic acid B and curcumin, successfully synthesizing the SC conjugate. Results are attached. Figure 1 As shown.

[0043] 2) Fourier Transform Infrared Spectroscopy (FTIR) Analysis: The SC conjugate, raw material salvianolic acid B, and curcumin were subjected to FTIR analysis using the KBr pellet method. Results showed that in the hydroxyl stretching vibration region, the raw material salvianolic acid B (3428 cm⁻¹) exhibited... -1 ) and curcumin (3416cm) -1 The characteristic broad peaks of the ) merged and shifted to 3405 cm⁻¹ in the SC spectrum. -1 The peak shape and intensity changed significantly, indicating that the phenolic hydroxyl groups were consumed during the reaction. In the carbonyl region, the starting material curcumin showed a peak intensity of 1701 cm⁻¹. -1 The characteristic peak of the β-diketone carbonyl group at 1742 cm⁻¹ is similar to that of the raw material salvianolic acid B. -1 The carbonyl peaks at 1711 cm⁻¹ all disappeared, and in the SC spectrum, the peaks at 1711 cm⁻¹ disappeared. -1A new strong absorption peak appears at [value], which is attributed to the stretching vibration of the carbonyl group in the newly formed ester bond (-COO-). The fingerprint region SC is at 1281 cm⁻¹. -1 An absorption peak appears at this point, attributed to the asymmetric stretching vibration of the COC in the ester bond. Aromatic skeleton vibration region (~1620 cm⁻¹). -1 With ~1515cm -1 The characteristic absorption of the raw materials was retained. The above results confirm that a dehydration condensation occurred between the carboxyl group of salvianolic acid B and the phenolic hydroxyl group of curcumin, forming a covalent ester bond. The results are attached. Figure 2 As shown.

[0044] 3) Ultraviolet (UV) Spectroscopy Analysis: Solutions of the SC conjugate, salvianolic acid B, and curcumin were prepared separately and subjected to UV scanning. The results showed that the characteristic absorption peak of curcumin at 350-500 nm was retained in the SC spectrum but underwent a blue shift (to approximately 400-450 nm); the strong absorption characteristics of salvianolic acid B at 300-400 nm were also observed in the SC spectrum, but the overall absorption profile was significantly different. This result confirms that the SC conjugates were not simply physically mixed, but rather formed a new chemical structure through covalent bonding. The results are attached. Figure 3 As shown.

[0045] 4) Transmission Electron Microscopy (TEM) Observation: An aqueous solution of the SC conjugate was dropped onto a copper grid, negatively stained with phosphotungstic acid, and observed under a TEM. The results showed that SC self-assembled in the aqueous phase to form well-dispersed spherical nanomicelles with an average particle size of 5-10 nm. The results are attached. Figure 4 As shown.

[0046] 5) Critical micelle concentration (CMC) determination: The critical micelle concentration of the SC conjugate was determined using the pyrene fluorescent probe method. A series of SC aqueous solutions were prepared, and pyrene was added to achieve a final concentration of 6.0 × 10⁻⁶. -7 The intensity ratio of the first and third fluorescence peaks of pyrene (I1 / I3) was measured at mol / L. A plot of I1 / I3 against the logarithm of concentration was plotted, and the critical micelle concentration of SC was calculated to be 189 μg / mL. The results are attached. Figure 5 As shown.

[0047] 6) Determination of drug loading and encapsulation efficiency: Using SC micelle solution, the absorbance of curcumin was measured at 425 nm using ultraviolet spectrophotometry. The curcumin content was calculated by substituting the absorbance into the standard curve. The encapsulation efficiency and drug loading efficiency were calculated using the following formula:

[0048] Encapsulation efficiency (%) = Mass of curcumin in micelles / Total mass of added curcumin × 100%;

[0049] Drug loading rate (%) = mass of curcumin in micelles / total mass of SC conjugates × 100%;

[0050] Calculations showed that the encapsulation efficiency of SC micelles for curcumin was 95.82%, and the drug loading rate was 32.47%.

[0051] 7) In vitro drug release kinetics evaluation: The in vitro drug release behavior of SC micelles was investigated using dialysis. PBS buffer (containing 0.5% Tween 80) at pH 2.0, pH 6.8, and pH 7.4 were used as release media. SC micelle solutions were placed in dialysis bags (molecular weight cutoff 3500 Da) and release experiments were conducted at 37℃ and 100 rpm. Samples were taken periodically, and isothermal replenishment of the same volume of fresh medium was performed to determine the cumulative release rate of curcumin. The results showed that at pH 2.0, the cumulative release rate was close to 80% after 96 hours; at pH 6.8 and pH 7.4, the cumulative release rate was approximately 40% during the same period. This indicates that SC micelles have pH-responsive sustained-release characteristics, with faster release under acidic conditions and slower release under neutral and weakly acidic conditions. Results are attached. Figure 6 As shown.

[0052] 8) DPPH free radical scavenging activity assay: SC conjugate solutions of different concentrations (0-400 μg / mL) and free curcumin solutions of equal concentration were prepared and mixed with DPPH ethanol solution. After reacting in the dark for 30 minutes, the absorbance was measured at 517 nm, and the DPPH free radical scavenging rate was calculated. The results showed that the scavenging rate of free curcumin at 400 μg / mL was approximately 60%; the scavenging rate of SC at the same concentration was approximately 83%, and a significant advantage was observed at concentrations below 100 μg / mL. This indicates that the antioxidant activity of SC was significantly superior to that of free curcumin, and that salvianolic acid B and curcumin produced a synergistic antioxidant effect through covalent linkage. (See attached results.) Figure 7 As shown.

[0053] 9) Zeta potential measurement: The zeta potentials of SC micelle solution, M2 macrophage membrane suspension, and SCM nanoparticle solution were measured using Zetasizer Nano ZS. The results showed that the zeta potential of SC micelles was -19.76±2.20 mV, that of M2 macrophage membrane was -4.64±0.17 mV, and that of SCM nanoparticles was -10.13±0.94 mV. The potential value of SCM was between that of SC and M2, confirming that the M2 macrophage membrane was successfully coated on the surface of SC micelles.

[0054] 10) UV Spectroscopic Verification of SCM: SC micelle solution, M2 macrophage membrane suspension, and SCM nanoparticle solution were subjected to UV scanning. Results showed that SC micelles exhibited characteristic absorption bands in the UV region; the absorption curves of the SCM nanoparticles were highly consistent with those of the M2 macrophage membrane in both shape and intensity, and the characteristic absorption peaks of SC were completely covered by the spectral characteristics of M2. This result confirms that the M2 macrophage membrane formed a continuous and complete coating layer on the surface of the SC micelles. (See attached image) Figure 8 As shown.

[0055] 11) Storage Stability: SC micelle solution and SCM nanoparticle solution were stored at 4℃, and samples were taken on days 1, 3, 5, and 7 to determine particle size and polydispersity index (PDI). Results showed that during the 7-day observation period, the particle size of SC micelles remained within the range of 10-15 nm, and the PDI fluctuated slightly between 0.35 and 0.40, exhibiting good colloidal stability. The particle size of SCM nanoparticles increased continuously from approximately 146 nm on day 1 to approximately 224 nm on day 7, and the PDI increased from 0.313 to 0.496, indicating that SCM is prone to aggregation and decreased structural stability during storage. It is recommended to use freshly prepared SCM immediately. See attached details. Figure 9 As shown.

[0056] It should be noted that the applications of the hydrogen bond self-assembly-based salvianolic acid β-curcumin macrophage membrane-coated nanoformulation provided in this invention are not limited to the following categories:

[0057] Preparation of oral formulations: The SCM nanoparticle formulation solution prepared in Example 1 is mixed with pharmaceutically acceptable excipients selected from one or more of fillers, binders, disintegrants, and lubricants, and prepared into an oral dosage form using conventional processes (wet granulation, dry granulation, direct tableting, or fluidized bed granulation). Oral dosage forms include, but are not limited to, tablets, capsules, granules, oral liquids, or powders.

[0058] Preparation of the injectable formulation: The SCM nanoparticle formulation solution prepared in Example 1 was filtered through a 0.22 μm sterile filter membrane, diluted with an appropriate amount of physiological saline or glucose solution for injection, and prepared into an injectable formulation according to a sterile filling process. The injectable formulation is for intravenous or intramuscular injection.

[0059] Preparation of lyophilized powder for injection: The SCM nano-formulation solution prepared in Example 1 was mixed with an appropriate amount of lyophilization protectant, which was selected from one or more of mannitol, sucrose, trehalose, and glucose. The mixture was then freeze-dried to prepare lyophilized powder for injection. The powder was reconstituted with water for injection before use.

[0060] The foregoing has only described certain exemplary embodiments of the present invention by way of illustration. Undoubtedly, those skilled in the art can modify the described embodiments in various ways without departing from the spirit and scope of the present invention. Therefore, the foregoing drawings and descriptions are illustrative in nature and should not be construed as limiting the scope of protection of the claims of the present invention.

Claims

1. A hydrogen-bonded self-assembled salvianolic acid β-curcumin macrophage membrane-coated nanoformulation, comprising salvianolic acid β-curcumin covalently conjugate self-assembled nanomicelles and an M2-type macrophage membrane coated on the surface of the nanomicelles, characterized in that, In the self-assembled nanomicelles of the salvianolic acid B-curcumin covalent conjugate, salvianolic acid B and curcumin are bonded by covalent ester bonds to form SC conjugates. The SC conjugates self-assemble into spherical nanomicelles through intermolecular hydrogen bonds. The M2 macrophage membrane is completely coated on the surface of the nanomicelles to form a core-shell structured SCM nanoformulation.

2. The hydrogen-bonded self-assembled salvianolic acid β-curcumin macrophage membrane-coated nanoparticle formulation according to claim 1, characterized in that, The SC conjugate nanomicelles have an average particle size of 5-10 nm, a critical micelle concentration of 189 μg / mL, and a Zeta potential of -10.13 ± 0.94 mV.

3. The hydrogen-bonded self-assembled salvianolic acid β-curcumin macrophage membrane-coated nanoformulation according to claim 1, characterized in that, The curcumin had an encapsulation rate of 95.82% and a drug loading rate of 32.47%.

4. A method for preparing a hydrogen-bonded self-assembled nanoparticle of salvianolic acid β-curcumin macrophage membrane as described in any one of claims 1-3, characterized in that, Includes the following steps: S1: Synthesis of salvianolic acid B-curcumin SC conjugate: 0.368 g curcumin was dissolved in 10 mL anhydrous DMSO, 0.41 g DCC and 0.24 g DMAP were added, and the carboxyl group was activated by stirring at room temperature for 30 min; 0.718 g salvianolic acid B was added, and the reaction was carried out at room temperature in the dark for 48 h; after filtering the reaction solution, diethyl ether was added to precipitate a dark orange precipitate, and the crude product was dialyzed through DMSO and ultrapure water in sequence, and freeze-dried to obtain a yellow powder SC conjugate; S2: Extraction of M2 macrophage membrane: RAW264.7 mouse macrophages were cultured to the logarithmic growth phase, washed with PBS and the cells were collected; the cells were resuspended in pre-cooled TM buffer, incubated overnight in a hypotonic atmosphere at 4°C, and homogenized to disrupt the cells; the sucrose concentration was adjusted to 0.25M, and the cells were removed by gradient centrifugation. The precipitate was washed to obtain purified macrophage membranes, which were stored at low temperature for later use. S3: Assembly of SCM nanoparticles: The purified M2 macrophage membrane was mixed evenly with the SC conjugate PBS solution, vortexed and incubated at 4°C for 12 h; the macrophage membrane-coated SCM nanoparticles were prepared by repeated extrusion through a 100 nm polycarbonate porous membrane.

5. The preparation method according to claim 4, characterized in that, The dialysis conditions in step S1 are: molecular weight cutoff 500 Da, dialysis with DMSO for 2 days, and dialysis with ultrapure water for 3 days.

6. The preparation method according to claim 4, characterized in that, In step S2, the TM buffer consisted of 10 mM Tris + 1 mM MgCl2, pH 7.4; the cell resuspending density was 3.0 × 10⁻⁶ cells / mL. 7 The concentration of PMSF was 1% of the system volume.

7. The preparation method according to claim 4, characterized in that, Centrifugation parameters in step S2: centrifuge at 4℃ and 2000rcf for 15 min to remove precipitate impurities, centrifuge at 3000rcf for 30 min to collect cell membrane precipitate, and wash 3 times with ice-cold™ buffer.

8. The preparation method according to claim 4, characterized in that, In step S3, the extrusion process is continuous extrusion using a micro extruder.

9. The use of a nano-formulation as described in any one of claims 1-3 in the preparation of a medicament for the prevention, delay, or treatment of atherosclerosis and related cardiovascular and cerebrovascular diseases.

10. The application according to claim 9, characterized in that, The drug is available in oral or injectable form.

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