Cordycepin nano-liposome, preparation thereof and application of cordycepin nano-liposome in treatment of lung injury

Abstract

The invention belongs to the technical field of specific therapeutic activity of compounds or pharmaceutical preparations, and particularly relates to a cordycepin nano-liposome, preparation and application of the cordycepin nano-liposome in treatment of lung injury. The cordycepin nano-liposome provided by the invention is composed of cordycepin, lecithin, cholesterol, dipalmitoyl phosphatidylcholine-polyethylene glycol and water-soluble pentosan, is prepared by adopting a film hydration method, and has high drug loading capacity, high bioavailability and excellent physical stability; precise lung targeted delivery is achieved by means of the synergistic effect of the components, and in-vivo experiments prove that the nano-liposome can effectively inhibit inflammatory response of the acute lung injury part and remarkably improve the lung injury symptom, provides an efficient treatment scheme for acute lung injury, and has important clinical transformation value and wide application prospects.

Description

Technical Field

[0001] This invention belongs to the field of specific therapeutic activity technology of compounds or pharmaceutical preparations, specifically relating to a cordycepin nanoliposome, its preparation and use in treating lung injury. Background Technology

[0002] Acute lung injury (ALI) is a common diffuse pulmonary inflammatory syndrome characterized by reduced lung volume, decreased lung compliance, and severe ventilation / perfusion mismatch. Clinically, it manifests as progressive hypoxemia and respiratory distress, while pulmonary imaging reveals heterogeneous exudative lesions. When lung damage in ALI progresses to a certain extent, it can easily develop into acute respiratory distress syndrome (ARDS), posing a serious threat to the patient's life and health. Existing research has clearly identified inflammatory response and oxidative stress as key components in the pathogenesis of ALI, making the development of targeted therapies against these two key mechanisms a hot research topic in this field.

[0003] Cordycepin (CAS: 73-03-0), chemically known as 3′-deoxyadenosine, is a nucleoside alkaloid with diverse pharmacological activities. Numerous studies have confirmed that cordycepin possesses antitumor, antiviral, antibacterial, immunomodulatory, and significantly anti-inflammatory effects. Its anti-inflammatory properties make it highly promising for the treatment of acute lung injury, providing a new candidate drug for this disease.

[0004] However, the clinical medicinal value of cordycepin is severely limited by its own physicochemical properties and in vivo metabolic characteristics: as a nucleoside alkaloid, cordycepin is easily degraded by adenosine deaminase in vivo, converting into 3′-deoxyinosine, which has no anti-inflammatory activity, leading to the loss of its physiological activity and significantly reducing its clinical therapeutic effect. Therefore, developing novel drug delivery systems that can improve the in vivo stability and bioavailability of cordycepin has become the key to overcoming its clinical application bottleneck.

[0005] Currently, some technologies have attempted to address the clinical application challenges of cordycepin. For example, Chinese patent CN117462498A discloses a method for preparing cordycepin multi-responsive microspheres. However, this method is cumbersome, has a long production cycle, and the resulting microspheres are relatively large, making targeted delivery and efficient absorption to the lungs difficult and limiting their application. Nanoliposomes, as a novel drug carrier, offer a promising approach to solving the application challenges of cordycepin due to their unique phospholipid bilayer structure: on the one hand, the phospholipid bilayer membrane provides physical protection for the encapsulated cordycepin, effectively isolating it from the action of adenosine deaminase and preventing its degradation and inactivation; on the other hand, liposomes possess good biocompatibility and targeting capabilities, enabling drug accumulation in lung lesions and further enhancing the in vivo anti-inflammatory activity of cordycepin.

[0006] Although Chinese patent CN106798725A has reported the application of cordycepin nanoliposomes in antitumor activity, this technology has significant drawbacks: low drug loading capacity, which cannot meet the dosage requirements for clinical treatment, and high energy consumption during preparation, which is not conducive to large-scale production. More importantly, there are currently no reports, either domestically or internationally, on the use of cordycepin nanoliposomes in the treatment of acute lung injury, and there is a lack of systematic research on their biological distribution and therapeutic efficacy in acute lung injury models.

[0007] Based on the above situation, developing a cordycepin nanoliposome with high loading capacity, high targeting, and low toxicity to achieve its efficient application in the treatment of acute lung injury would not only fill the existing technological gap, but also be of great significance for promoting the clinical translation of cordycepin and improving the treatment prognosis of patients with acute lung injury, and has urgent clinical demand and broad application prospects. Summary of the Invention

[0008] This invention aims to overcome the shortcomings of existing technologies, such as complex preparation processes, low drug loading, poor targeting, and difficulty in meeting the treatment needs of acute lung injury. It provides a cordycepin nanoliposome with high drug loading, high stability, strong targeting, and excellent biocompatibility, as well as a simple and feasible preparation method suitable for large-scale production, and clarifies its application in the treatment of acute lung injury.

[0009] The cordycepin nanoliposomes of the present invention are composed of active ingredient of formula I (cordycepin), lecithin, cholesterol, dipalmitoylphosphatidylcholine-polyethylene glycol (DPPC-PEG), and water-soluble pentosan in a specific mass ratio, specifically: active ingredient of formula I: lecithin: cholesterol: dipalmitoylphosphatidylcholine-polyethylene glycol: water-soluble pentosan = 5: (24-32): (4-6): (8-12): (0.3-0.8).

[0010] The chemical name of the active ingredient of Formula I is 3′-deoxyadenosine (Cordycepin, CAS: 73-03-0), and its chemical structure is as follows: .

[0011] The cordycepin nanoliposomes have an average particle size of 80–180 nm, exhibit a uniform size distribution, and demonstrate excellent physical stability.

[0012] The cordycepin nanoliposomes of this invention are prepared by a thin-film hydration method, and the specific steps are as follows:

[0013] (1) Raw material dissolution and film preparation: Lecithin, cholesterol and dipalmitoylphosphatidylcholine-polyethylene glycol are dissolved in an organic solvent, and after ultrasonic treatment to ensure complete dissolution, they are placed in a rotary evaporator and the solvent is removed by rotary evaporation at 50~55℃ to form a uniform lipid film; wherein, the organic solvent is selected from at least one of chloroform, ethanol and methanol.

[0014] (2) First hydration: Dissolve the active ingredient of Formula I in a partial phosphate buffer solution to obtain a dispersion. Add the dispersion to the above lipid film and perform a first hydration to make the lipid film initially swell. The mass ratio of the active ingredient of Formula I to the total volume of the phosphate buffer is 1 mg: 0.5-1.5 mL.

[0015] (3) Secondary hydration: Dissolve the water-soluble pentosan in the remaining phosphate buffer solution and add it to the primary hydration system to continue secondary hydration.

[0016] (4) Dispersion and molding treatment: The system after secondary hydration is placed in an ice bath and ultrasonically dispersed at a power of 150-200W for 10-30 minutes to obtain a uniform liposome suspension. The suspension is then extruded and molded by an extruder to obtain cordycepin nanoliposomes.

[0017] The cordycepin nanoliposomes of the present invention are used to prepare drugs for treating acute lung injury, achieving targeted enrichment of drugs in lung lesions and significantly improving the inflammatory response at the site of lung injury.

[0018] Compared with the prior art, the technical advantages of the present invention are as follows:

[0019] (1) High drug loading and high bioavailability: Through the specific component mass ratio and the step-by-step process design of "one-time hydration of cordycepin buffer + two-time hydration of pentosan buffer", the drug loading of the cordycepin nanoliposomes prepared by this invention reaches 8.8%~9.5%, which is significantly higher than that of liposomes without pentosan or using other processes; its blood drug concentration-time curve area AUC0-∞ in mice reaches 5629.4 ng·h / mL, which is far superior to cordycepin raw material (857.7 ng·h / mL), greatly improving the in vivo bioavailability of cordycepin.

[0020] (2) Excellent stability: The cordycepin nanoliposomes prepared by this invention have uniform particle size and no significant change in particle size during storage at room temperature for 2 months. They have good physical stability and solve the problems of easy aggregation and poor stability of traditional liposomes.

[0021] (3) Precise lung targeting: With the help of the biocompatibility of liposomes and the modification effect of DPPC-PEG, the cordycepin nanoliposomes of the present invention can achieve lung-targeted delivery. In vivo biodistribution experiments have confirmed that it has a significant enrichment effect in the lungs and can accurately act on the lesion site of acute lung injury, reduce the distribution of drugs in other organs, and reduce potential toxic side effects.

[0022] (4) The preparation process is simple and feasible: The present invention adopts the thin film hydration method, which has simple process steps, controllable operation, no need for complex equipment, low energy consumption, short production cycle, and is suitable for large-scale industrial production. It overcomes the defects of the existing cordycepin microsphere preparation process, which is complicated, has a long production cycle, and high energy consumption.

[0023] (5) Significant anti-inflammatory therapeutic effect: In vivo treatment experiments have confirmed that the cordycepin nanoliposomes of the present invention can effectively inhibit the inflammatory response at the site of acute lung injury, significantly improve the symptoms of lung injury, provide an efficient treatment plan for acute lung injury, and fill the technical gap of cordycepin nanoliposomes for the treatment of acute lung injury. Attached Figure Description

[0024] Figure 1 Transmission electron microscopy image of cordycepin nanoliposomes prepared in Example 1.

[0025] Figure 2 Dynamic light scattering spectrum of cordycepin nanoliposomes prepared in Example 1.

[0026] Figure 3 Stability spectrum of cordycepin nanoliposomes prepared in Example 1.

[0027] Figure 4 Cytotoxicity profile of cordycepin nanoliposomes prepared in Example 1.

[0028] Figure 5In vivo biodistribution map of cordycepin raw material and cordycepin nanoliposomes prepared in Example 1.

[0029] Figure 6 In vivo blood concentration chromatograms of cordycepin raw material and cordycepin nanoliposomes prepared in Example 1.

[0030] Figure 7 In vivo therapeutic effects and serum inflammatory factor expression levels of cordycepin raw material and cordycepin nanoliposomes prepared in Example 1 (A: mouse lung tissue; B: HE-stained pathological image; C: TNF-α level; D: IL-1β level; E: IL-6 level).

[0031] Figure 8 Dynamic light scattering spectrum of cordycepin nanoliposomes prepared in Example 2.

[0032] Figure 9 Dynamic light scattering spectrum of cordycepin nanoliposomes prepared in Example 3.

[0033] Figure 10 Dynamic light scattering spectrum of cordycepin microliposomes prepared by reverse emulsion method in Comparative Example 1.

[0034] Figure 11 Comparative Example 2: Dynamic light scattering spectrum of cordycepin microliposomes prepared by freeze-drying. Detailed Implementation

[0035] To make the objectives and technical solutions of this invention clearer, the following embodiments are provided for further explanation. However, the scope of protection of this invention is not limited to these embodiments; the embodiments are merely for illustrative purposes. Those skilled in the art should understand that any changes or equivalent substitutions that do not depart from the concept of this invention are included within the scope of protection of this invention.

[0036] Particle size and TEM analysis methods

[0037] The particle size distribution of cordycepin nanoliposomes was determined using a laser particle size analyzer to evaluate their physical stability and particle size characteristics. Simultaneously, the microstructure of the cordycepin nanoliposomes was observed using a transmission electron microscope. Specifically, the cordycepin nanoliposomes were diluted with purified water to an appropriate concentration. A suitable amount of the suspension was then added dropwise to 5 μL of a 1% (w / w) phosphotungstic acid aqueous solution for negative staining for 2 min. The stained suspension was then dropped onto a copper mesh surface, and excess liquid was removed by gently touching it with filter paper. The mesh was then allowed to air dry at room temperature. After drying, the morphology and structure were observed under a scanning electron microscope.

[0038] Biodistribution imaging of cordycepin nanoliposomes in vivo

[0039] Cy5-labeled cordycepin nanoliposomes were instilled into anesthetized mice via intratracheal instillation. Whole-body fluorescence images were acquired 4 hours later, and major organs were isolated. Fluorescence intensity was measured to assess their biodistribution.

[0040] Method for determining cordycepin blood concentration in mice

[0041] Samples were separated using a Shimadzu Nexera X2LC-30AD ultra-high performance liquid chromatography (UHPLC) system. Mobile phases: Solution A was 0.1% FA aqueous solution, and Solution B was 0.1% FA acetonitrile. Samples were placed in an autosampler at 4℃, column temperature 35℃, flow rate 1.0 mL / min, and injection volume 1 μL. The relevant HPLC gradients were as follows: 0–6 min, Solution B linearly changed from 10% to 90%; 6–7 min, Solution B maintained 90%; 7–7.5 min, Solution B linearly changed from 90% to 10%; 7.5–10 min, Solution B maintained 10%. Cordycepin was analyzed by mass spectrometry in positive spectrum mode.

[0042] Example 1: Cordycepin nanoliposomes

[0043] 24 mg of lecithin, 4 mg of cholesterol, and 8 mg of dipalmitoylphosphatidylcholine-polyethylene glycol were placed in a 50 mL rotary evaporator flask, and 35 mL of chloroform were added. The ultrasonic frequency was adjusted to 30 Hz, and the ultrasonic time was 20 min to ensure complete dissolution. The dissolved liquid was then placed in a rotary evaporator and evaporated under vacuum at 50 ℃ for 40 min to obtain a lipid membrane. Subsequently, 5 mg of cordycepin was dissolved in 4.5 mL of phosphate buffer to obtain a dispersion. The cordycepin dispersion was then placed in the lipid membrane for primary hydration. 0.5 mg of water-soluble pentosan was dissolved in 3 mL of phosphate buffer and added to the primary hydration system for secondary hydration. After ultrasonication at 175 W in an ice bath for 15 min, the dispersion was extruded 20 times through a liposome extruder to obtain cordycepin nanoliposomes.

[0044] Figure 1 This is a transmission electron microscope (TEM) image of the cordycepin nanoliposomes prepared in Example 1. Figure 1 It can be seen that the cordycepin nanoliposomes exhibit a uniform size distribution, and their average particle size is 174.8 nm. Figure 2 The dynamic light scattering spectrum of the cordycepin nanoliposomes prepared in Example 1 is shown below. Figure 2 It can be seen that the cordycepin nanoliposomes exhibit a single peak and a narrow half-peak width, indicating that the prepared cordycepin nanoliposomes have a uniform particle size and an average hydrated particle size of 175 nm. Figure 3 The stability spectrum of the cordycepin nanoliposomes prepared in Example 1 is shown below. Figure 3It can be seen that the particle size of cordycepin nanoliposomes did not change significantly during the two-month storage period at room temperature, indicating that they have excellent stability. Figure 4 The cytotoxicity profile of the cordycepin nanoliposomes prepared in Example 1 is shown below. Figure 4 This demonstrates that cordycepin nanoliposomes have excellent biocompatibility. Figure 5 The in vivo biodistribution profiles of cordycepin raw material and cordycepin nanoliposomes prepared in Example 1 are provided by... Figure 5 This demonstrates that cordycepin nanoliposomes have excellent lung targeting properties. Figure 6 The blood concentration profiles of cordycepin raw material and cordycepin nanoliposomes prepared in Example 1 in mice are shown in the figure. Figure 6 This indicates that the highest plasma concentration of cordycepin raw material in mice was 234.52 ng / mL, and the area under the plasma concentration-time curve (AUC) was [data missing]. 0-∞ The concentration was 857.7 ng·h / mL. However, the cordycepin nanoliposomes obtained in this invention released a significantly higher plasma concentration of cordycepin in mice than the raw cordycepin drug, with a significantly higher area under the plasma concentration-time curve (AUC). 0-∞ The concentration was 5629.4 ng·h / mL, which greatly improved the in vivo bioavailability of cordycepin raw material. Figure 7 The in vivo therapeutic efficacy profiles of cordycepin raw material and cordycepin nanoliposomes prepared in Example 1 are shown in the figure. Figure 7 This demonstrates that cordycepin nanoliposomes can significantly improve the inflammatory response at the site of lung injury.

[0045] Example 2 Cordycepin Nanoliposomes

[0046] 24 mg of lecithin, 4 mg of cholesterol, and 12 mg of dipalmitoylphosphatidylcholine-polyethylene glycol were placed in a 50 mL rotary evaporator flask, and 35 mL of methanol was added. The ultrasonic frequency was adjusted to 25 Hz, and the ultrasonic time was 30 min to ensure complete dissolution. The dissolved liquid was then placed in a rotary evaporator and evaporated under vacuum at 52 °C for 60 min to obtain a lipid membrane. Subsequently, 5 mg of cordycepin was dissolved in 3 mL of phosphate buffer to obtain a dispersion. The cordycepin dispersion was then placed in the lipid membrane for primary hydration. 0.3 mg of water-soluble pentosan was dissolved in 2 mL of phosphate buffer and added to the primary hydration system for secondary hydration. After ultrasonication at 150 W for 10 min in an ice bath, the dispersion was extruded 25 times through a liposome extruder to obtain cordycepin nanoliposomes.

[0047] Figure 8 The dynamic light scattering spectrum of the cordycepin nanoliposomes prepared in Example 2 is shown below. Figure 8It can be seen that the cordycepin nanoliposomes exhibit a single peak and a narrow half-peak width, indicating that the prepared cordycepin nanoliposomes have a uniform particle size and an average hydrated particle size of 175 nm. Figure 8 and Figure 2 The comparison demonstrates that the cordycepin nanoliposomes prepared in Example 2 and Example 1 are the same substance. Testing showed that their in vivo targeting, long-term storage stability, and blood drug concentration in mice were similar to those in Example 1.

[0048] Example 3 Cordycepin Nanoliposomes

[0049] 32 mg of lecithin, 6 mg of cholesterol, and 12 mg of dipalmitoylphosphatidylcholine-polyethylene glycol were placed in a 50 mL rotary evaporator flask, and 32 mL of ethanol was added. The ultrasonic frequency was adjusted to 30 Hz, and the ultrasonic time was 30 min to ensure complete dissolution. The dissolved liquid was then placed in a rotary evaporator and evaporated under vacuum at 55 °C for 60 min to obtain a lipid membrane. Subsequently, 5 mg of cordycepin was dissolved in 3 mL of phosphate buffer to obtain a dispersion. The cordycepin dispersion was then placed in the lipid membrane for primary hydration. 0.8 mg of water-soluble pentosan was dissolved in 4.5 mL of phosphate buffer and added to the primary hydration system for secondary hydration. After ultrasonication at 175 W in an ice bath for 30 min, the dispersion was extruded 30 times through a liposome extruder to obtain cordycepin nanoliposomes.

[0050] Figure 9 The dynamic light scattering spectrum of the cordycepin nanoliposomes prepared in Example 3 is shown below. Figure 9 It can be seen that the cordycepin nanoliposomes exhibit a single peak and a narrow half-peak width, indicating that the prepared cordycepin nanoliposomes have a uniform particle size and an average hydrated particle size of 175.4 nm. Figure 9 and Figure 2 The comparison demonstrates that the cordycepin nanoliposomes prepared in Example 3 and Example 1 are the same substance. Testing showed that their in vivo targeting, long-term storage stability, and blood drug concentration in mice were similar to those in Example 1.

[0051] Comparative Example 1: Cordycepin Nanoliposomes

[0052] The only difference from Example 1 is that the thin film hydration method in Example 1 is replaced with the reverse emulsion method; all other preparation methods are the same as in Example 1.

[0053] Dynamic optical testing and analysis were performed on cordycepin liposomes prepared by the reverse emulsion method. Figure 10 The image shows the dynamic light scattering pattern of cordycepin liposomes prepared by the reverse emulsion method in Comparative Example 1. The pattern shows a non-uniform size distribution and an average hydrated particle size of 850.3 nm.

[0054] The comparison between Example 1 and Comparative Example 1 shows that uniform cordycepin nanoliposome particles cannot be prepared by the reverse emulsion method.

[0055] Comparative Example 2: Cordycepin Nanoliposomes

[0056] The only difference from Example 1 is that the thin-film hydration method was not used; instead, the freeze-drying method was used to attempt to obtain cordycepin nanoliposomes.

[0057] Dynamic optical testing and analysis were performed on cordycepin liposomes prepared by freeze-drying. Figure 11 The image shows the dynamic light scattering pattern of cordycepin liposomes prepared by freeze-drying in Comparative Example 2. The pattern shows a non-uniform size distribution and an average hydrated particle size of 1406.9 nm.

[0058] The comparison between Example 1 and Comparative Example 2 shows that uniform cordycepin nanoliposome particles cannot be prepared by freeze-drying.

[0059] Comparative Example 3: Cordycepin Nanoliposomes

[0060] The only difference from Example 1 is that the cordycepin nanoliposomes were obtained without the addition of pentosan.

[0061] Comparative Example 4: Cordycepin Nanoliposomes

[0062] The only difference from Example 1 is that no pentosan was added, but an equal amount of β-glucan was added to obtain cordycepin nanoliposomes.

[0063] Comparative Example 5: Cordycepin Nanoliposomes

[0064] The only difference from Example 1 is that no pentosan was added, but an equal amount of hyaluronic acid as pentosan in Example 1 was added to obtain cordycepin nanoliposomes.

[0065] Comparative Example 6: Cordycepin Nanoliposomes

[0066] The only difference from Example 1 is that no pentosan was added, but an equal amount of water-soluble chitosan as in Example 1 was added to obtain cordycepin nanoliposomes.

[0067] Comparative Example 7: Cordycepin Nanoliposomes

[0068] The only difference from Example 1 is that in the preparation method, pentosan and cordycepin are dissolved together in phosphate buffer for hydration, without stepwise hydration, resulting in cordycepin nanoliposomes.

[0069] Comparative Example 8: Cordycepin Nanoliposomes

[0070] The only difference from Example 1 is that the first hydration in the preparation method uses pentosan-phosphate buffer, and the second hydration uses cordycepin-phosphate buffer, resulting in cordycepin nanoliposomes.

[0071] Determination of drug loading capacity of cordycepin nanoliposomes

[0072] Drug loading is the percentage of cordycepin encapsulated in liposomes relative to the total mass of the liposomes, calculated using the formula: DL(%) = (mass of encapsulated cordycepin / total mass of liposomes) × 100%. The drug loading was calculated by separating the free drug from the liposome-encapsulated drug and determining the drug concentration using ultra-high performance liquid chromatography (UPLC).

[0073] Table 1. Drug loading capacity of cordycepin nanoliposomes

[0074] Table 1 shows that the drug loading of cordycepin nanoliposomes prepared in Examples 1-3 of this invention is 8.8%~9.5%, which is significantly higher than that of all comparative examples 3-8. This clarifies that water-soluble pentosan is the core component for improving drug loading, and that the stepwise process and sequence of "one-time hydration of cordycepin buffer + two-time hydration of pentosan buffer" is a necessary condition for achieving high drug loading. At the same time, it verifies that the component mass ratio range defined by this invention has good process stability, further proving the rationality of the formulation design and preparation process, and effectively solving the defect of low drug loading of cordycepin liposomes in the prior art.

Claims

1. A cordycepin nanoliposome, characterized in that, The cordycepin nanoliposomes contain the following components in a mass ratio of 5:(24-32):(4-6):(8-12):(0.3-0.8): active ingredient of formula I, lecithin, cholesterol, dipalmitoylphosphatidylcholine-polyethylene glycol, and water-soluble pentosan. (Formula I).

2. The cordycepin nanoliposomes according to claim 1, characterized in that, The average particle size of the cordycepin nanoliposomes is 80–180 nm.

3. The cordycepin nanoliposomes according to claim 1, characterized in that, The cordycepin nanoliposomes were prepared using a thin-film hydration method.

4. The cordycepin nanoliposomes according to claim 3, characterized in that, The thin-film hydration method includes the following steps: (1) Raw material dissolution and film preparation: Lecithin, cholesterol and DPPC-PEG are dissolved in an organic solvent, and the solvent is removed by rotary evaporation to form a lipid film; (2) Primary hydration: The active ingredient of Formula I is partially dissolved in a buffer solution and added to the lipid film for primary hydration, so that the film is initially swollen; (3) Secondary hydration: The water-soluble pentosan is dissolved in the remaining buffer solution and added to the primary hydration system for secondary hydration; (4) Dispersion and molding treatment: The secondary hydration system is ultrasonically dispersed to obtain a uniform liposome suspension, which is then extruded and molded to obtain cordycepin nanoliposomes.

5. The cordycepin nanoliposomes according to claim 4, characterized in that, The organic solvent is selected from at least one of chloroform, ethanol, and methanol.

6. The cordycepin nanoliposomes according to claim 4, characterized in that, The buffer solution is a phosphate buffer solution.

7. The cordycepin nanoliposomes according to claim 4, characterized in that, The rotary evaporation temperature is 50~55℃.

8. The cordycepin nanoliposomes according to claim 4, characterized in that, The mass ratio of the active ingredient of Formula I to the volume ratio of the phosphate buffer is 1 mg: 0.5–1.5 mL.

9. The cordycepin nanoliposomes according to claim 4, characterized in that, The conditions for ultrasonic dispersion are 150-200 W ice bath ultrasound for 10-30 minutes.

10. Use of the cordycepin nanoliposomes of claim 1 in the preparation of a drug for treating acute lung injury.

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