Astragaloside nanoformulation for treatment of hepatitis b and preparation method therefor

Abstract

An astragaloside nanoformulation for the treatment of hepatitis B and a preparation method therefor. The astragaloside nanoformulation for the treatment of hepatitis B comprises astragaloside and an auxiliary material. The auxiliary material comprises at least one of a polyoxyethylene-polyoxypropylene ether triblock copolymer, phospholipid, albumin, and casein. The compounding of these auxiliary materials and astragaloside can result in an astragaloside nanoformulation with good water solubility and high bioavailability, which exhibits higher safety and efficacy for the treatment of hepatitis B.

Description

Astragaloside nanoparticle preparation for treating hepatitis B and preparation method thereof

[0001] This application claims priority to the Chinese patent application filed with the China Patent Office on March 29, 2024, with application number 202410381886.2 and invention name “A nanoformulation of astragaloside for treating hepatitis B and its preparation method”, the entire contents of which are incorporated by reference into this application. Technical Field

[0002] The present application belongs to the technical field of pharmaceutical preparations, and in particular relates to an astragaloside nanoformulation for treating hepatitis B and a preparation method thereof. Background Art

[0003] Hepatitis B (HBV) generally refers to viral hepatitis type B. It is a common clinical infectious disease caused by the hepatitis B virus (HBV) infecting the liver and can lead to chronic infection. Hepatitis B is closely associated with cirrhosis and hepatocellular carcinoma (primary liver cancer).

[0004] Currently, hepatitis B is primarily treated with antiviral drugs, most commonly pegylated interferon and nucleos(o)ide drugs. While antiviral drugs can effectively inhibit viral replication, they suffer from low response rates, numerous adverse reactions, and difficulty clearing hepatitis surface antigens from the body. Currently, there is no cure for hepatitis B. Therefore, a safe and effective treatment is urgently needed. Technical issues

[0005] The purpose of the embodiments of the present application is to provide an astragaloside nanoformulation for treating hepatitis B and a preparation method thereof. Technical Solutions

[0006] The technical solution adopted in the embodiment of this application is:

[0007] In a first aspect, the present application provides an astragaloside nanoformulation for treating hepatitis B, comprising: astragaloside IV and excipients, wherein the excipients include at least one of polyoxyethylene polyoxypropylene ether triblock copolymer, phospholipid, albumin, and casein.

[0008] In some embodiments, the mass ratio of the astragaloside IV to the excipient is 1:(1-4).

[0009] In some embodiments, the astragaloside nanoformulation comprises a nanoparticle formulation.

[0010] In some embodiments, the astragaloside nanoformulation has an average particle size of less than or equal to 700 nm and a polydispersity index of less than or equal to 0.3.

[0011] In some embodiments, the excipient is a polyoxyethylene polyoxypropylene ether triblock copolymer, and the average particle size of the astragaloside nanoformulation is 60-600 nm, and the polydispersity index is 0.25-0.30.

[0012] In a second aspect, the present application provides a method for preparing the above-mentioned astragaloside nanoformulation, comprising:

[0013] The astragaloside IV and the auxiliary materials are mixed and then subjected to thin film hydration treatment to obtain the astragaloside IV nano preparation.

[0014] In some embodiments, the step of mixing the astragaloside IV and the excipients and then subjecting them to a thin film hydration treatment comprises:

[0015] The astragaloside IV and the auxiliary materials are dissolved in an organic solvent, and then the solvent is removed by rotary evaporation to form a film; the film is mixed with a glucose aqueous solution for hydration treatment, and then ultrasonically dispersed.

[0016] In some embodiments, the organic solvent comprises an alcohol solvent.

[0017] In some embodiments, the mass fraction of glucose in the glucose aqueous solution is 4-6%.

[0018] In some embodiments, the volume ratio of the mass of the astragaloside IV to the glucose aqueous solution is 1 mg: 0.1-0.2 mL. Beneficial effects

[0019] The beneficial effects of the astragaloside nanoformulation provided in the embodiments of the present application are as follows: the astragaloside nanoformulation uses unique excipients, namely, at least one of polyoxyethylene polyoxypropylene ether triblock copolymer, phospholipids, albumin, and casein; these excipients and astragaloside IV are combined to form an astragaloside nanoformulation with good water solubility and high bioavailability; and experiments have shown that the astragaloside nanoformulation of the present application can treat hepatitis B more safely and effectively, providing a new therapeutic drug preparation for the treatment of hepatitis B.

[0020] The beneficial effect of the preparation method of the astragaloside IV nanoformulation provided in the examples of this application is that it uses a thin film hydration method to mix astragaloside IV with excipients to form the astragaloside IV nanoformulation. This preparation method is not only simple, but also produces an astragaloside IV nanoformulation with good water solubility and high bioavailability, making it highly suitable for the treatment of hepatitis B. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following briefly introduces the drawings required for use in the embodiments or exemplary technical descriptions. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0022] FIG1 is a sedimentation diagram of astragaloside nanoparticles of various prescriptions formed with different excipients;

[0023] FIG2 is a transmission electron micrograph of astragaloside nanoparticles provided in an embodiment of the present application;

[0024] FIG3 is a comparison diagram of the infrared spectra of astragaloside IV (AS-IV) provided in the examples of the present application;

[0025] FIG4 is a comparison chart of infrared spectra of the auxiliary material polyoxyethylene polyoxypropylene ether triblock copolymer (Pluronic® F-127) provided in the examples of the present application;

[0026] FIG5 is a comparison diagram of infrared spectra of astragaloside nanoparticles (P-AS) provided in the examples of the present application;

[0027] FIG6 is a comparison diagram of infrared spectra of the Pluronic® F-127 / AS-IV mixture (Mix) provided in the examples of the present application;

[0028] FIG7 is a comparison of HBsAg in vivo after treatment with different astragaloside nanoparticles provided in the examples of the present application;

[0029] FIG8 is a comparison diagram of HBs Ag in vivo after the astragaloside Pluronic nanoparticles provided in the examples of the present application treated an animal model with high HBs Ag levels;

[0030] FIG9 is a graph showing the body weight curve after treatment with Astragaloside Pluronic Nanoparticles provided in the Examples of the present application. Modes for Carrying Out the Invention

[0031] In order to make the purpose, technical solutions and advantages of this application more clear, the following further describes this application in detail with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain this application and are not intended to limit this application.

[0032] In this application, the term "and / or" describes the relationship between associated objects, indicating that three possible relationships exist. For example, A and / or B can represent: A exists alone, A and B exist simultaneously, and B exists alone. A and B can be singular or plural. The character " / " generally indicates that the associated objects are in an "or" relationship.

[0033] In this application, "at least one" means one or more, "more than one" means two or more. "At least one of the following" or similar expressions refers to any combination of these items, including any combination of single or plural items.

[0034] It should be understood that in the various embodiments of the present application, the serial numbers of the above-mentioned processes do not mean the order of execution. Some or all of the steps can be executed in parallel or sequentially. The execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0035] The terms used in the embodiments of the present application are only for the purpose of describing specific embodiments and are not intended to limit the present application. The singular forms "a", "an", "the" and "the" used in the embodiments of the present application and the appended claims are also intended to include plural forms unless the context clearly indicates otherwise.

[0036] The weights of the relevant components mentioned in the examples of this application may not only refer to the specific content of each component, but also represent the weight ratio between the components. Therefore, as long as the content of the relevant components is proportionally increased or decreased according to the examples of this application, it is within the scope disclosed in the examples of this application. Specifically, the mass described in the examples of this application may be a mass unit known in the medical field, such as μg, mg, g, kg, etc.

[0037] The terms "first" and "second" are used solely for descriptive purposes to distinguish objects, such as substances, from one another and should not be understood to indicate or imply relative importance or to implicitly specify the quantity of the technical features being referred to. For example, without departing from the scope of the embodiments of this application, a first XX may also be referred to as a second XX, and similarly, a second XX may also be referred to as a first XX. Thus, features defined as "first" or "second" may explicitly or implicitly include one or more of such features.

[0038] Astragaloside IV (AS-IV) is a lanolin alcohol-type tetracyclic triterpenoid saponin and one of the main active ingredients in the traditional Chinese medicine Astragalus membranaceus. It exhibits multiple effects, including anti-inflammatory, antioxidant, antiviral, and immunomodulatory. However, AS-IV has poor water solubility, typically only 0.05 mg / ml in water, and low oral bioavailability, seriously limiting its application. Therefore, pharmaceutical formulation technologies are needed to address the water solubility and bioavailability challenges of AS-IV.

[0039] Based on this, the present invention screened some excipients and compounded them with astragaloside IV to develop an astragaloside IV nanoformulation with better performance and its preparation method. Such an astragaloside IV nanoformulation can be well used to treat hepatitis B. The specific scheme is as follows.

[0040] In a first aspect, an embodiment of the present application provides a nano-preparation of astragaloside IV for treating hepatitis B, comprising: (1) a pharmaceutically active ingredient: astragaloside IV; and (2) an excipient, comprising at least one of a polyoxyethylene polyoxypropylene ether triblock copolymer, a phospholipid, albumin, and casein, wherein the excipient can be compounded with astragaloside IV to form a nano-preparation.

[0041] In the embodiments of the present application, a polyoxyethylene polyoxypropylene ether triblock copolymer, phospholipids, albumin and casein and at least one of astragaloside IV are compounded to form an astragaloside IV nanoformulation with good water solubility and high bioavailability; and the astragaloside IV nanoformulation of the embodiments of the present application can treat hepatitis B more safely and effectively, providing a new therapeutic drug preparation for the treatment of hepatitis B.

[0042] A large number of excipients were screened in the examples of this application, specifically, polyoxyethylene polyoxypropylene ether triblock copolymers (such as Pluronic® F-127), phospholipids (Lip), cyclodextrin derivatives [such as methyl-β-cyclodextrin (M-β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), etc.], polyvinyl pyrrolidone (such as PVP K15 、PVP K17 、PVP K30 etc.), polylactic acid (PLA), polylactic acid-glycolic acid copolymer (PLGA), polyoxyethylene sorbitan fatty acid esters (such as Tween-20 / TW20, Tween-80 / TW80, etc.), polyethylene glycol (such as PEG 8000 PEG 10000 PEG 20000 The researchers used astragaloside IV as a nanoformulation by saturating the loading of these excipients with various excipients, screening for suitable excipients. The nanoformulation, which included astragaloside IV and at least one of polyoxyethylene polyoxypropylene ether triblock copolymer, phospholipids, albumin, and casein, demonstrated superior stability and performance. Furthermore, the nanoformulation was validated in a mouse model for the treatment of hepatitis B, providing a promising therapeutic agent.

[0043] In some embodiments, the astragaloside IV nanoformulation formed by combining astragaloside IV and the above-screened excipients includes a nanoparticle preparation.

[0044] In some embodiments, the mass ratio of astragaloside IV to the screened excipient is 1:(1-4). For example, the mass ratio can be 1:1, 1:2, 1:3, 1:4, etc. The astragaloside IV nanoformulations prepared within this mass ratio range have a better therapeutic effect on hepatitis B.

[0045] In some embodiments, the average particle size of the astragaloside IV nanoformulation is less than or equal to 700 nm, and the polydispersity index is less than or equal to 0.3. The astragaloside IV nanoformulation within this parameter range has good stability and is uniformly dispersed.

[0046] In some embodiments, the excipient is a polyoxyethylene polyoxypropylene ether triblock copolymer, and the average particle size of the astragaloside IV nanoformulation is 60-600 nm, with a polydispersity index (PDI) of 0.25-0.30. Specifically, the polyoxyethylene polyoxypropylene ether triblock copolymer can be Pluronic® F-127. As a nonionic surfactant, the polyoxyethylene polyoxypropylene ether triblock copolymer has low cytotoxicity. Astragaloside IV nanoparticles prepared by a thin film hydration method not only increase the water solubility of astragaloside IV but also improve its bioavailability and enhance its anti-hepatitis B activity. Its therapeutic efficacy against hepatitis B has been validated in a mouse model.

[0047] The second aspect of the present invention provides a method for preparing an astragaloside nanoformulation, comprising the following steps:

[0048] S01: Providing astragaloside IV and excipients, wherein the excipients include at least one of a polyoxyethylene polyoxypropylene ether triblock copolymer, a phospholipid, albumin, and casein;

[0049] S02: Astragaloside IV and auxiliary materials are mixed and subjected to thin film hydration treatment to obtain an astragaloside IV nanoformulation.

[0050] The present invention adopts a thin film hydration method to mix astragaloside IV with excipients to prepare an astragaloside IV nanoformulation. The preparation method of the present invention is not only simple in process, but also the obtained astragaloside IV nanoformulation has good water solubility and high bioavailability, and can be used to treat hepatitis B.

[0051] In some embodiments, the excipient is further a polyoxyethylene polyoxypropylene ether triblock copolymer. The mass ratio of astragaloside IV to these excipients is 1:(1-4).

[0052] In some embodiments, the step of mixing astragaloside IV and the excipients and then subjecting the mixture to a thin film hydration treatment comprises:

[0053] Astragaloside IV and auxiliary materials are dissolved in an organic solvent, and then the solvent is removed by rotary evaporation to form a film; the film is mixed with a glucose aqueous solution for hydration treatment, and then ultrasonically dispersed.

[0054] In some embodiments, the organic solvent comprises an alcohol solvent. Furthermore, the mass fraction of glucose in the glucose aqueous solution is 4-6%. The volume ratio of astragaloside IV to the glucose aqueous solution is 1 mg: 0.1-0.2 mL.

[0055] Specifically, required excipients such as Pluronic® F-127 and astragaloside IV are weighed, dissolved in an alcohol solvent, and the organic solvent is removed by a rotary evaporator to form a thin film. A glucose aqueous solution is then added for hydration, and then ultrasonic dispersion is performed using an ice bath probe to obtain Pluronic® F-127-loaded astragaloside IV nanoparticles. Specifically, the astragaloside IV nanoparticles can be dispersed in a glucose aqueous solution in the form of nanoparticles and then stored in the dark at 4°C for later use.

[0056] The following describes the details in conjunction with specific embodiments.

[0057] Example 1 Preparation of Astragaloside Nanoparticles

[0058] (1) Preparation method

[0059] 200 mg of Pluronic® F-127 and 60 mg of astragaloside IV were weighed and dissolved in ethanol. The organic solvent was removed by rotary evaporation to form a thin film. 10 ml of 5% glucose solution was added for hydration. The film was then dispersed by ultrasonication using an ice-bath probe to obtain Pluronic® F-127-loaded astragaloside nanoparticles (P-AS). The film was stored at 4°C in the dark.

[0060] Cyclodextrin derivatives (methyl-β-cyclodextrin, M-β-CD; hydroxypropyl-β-cyclodextrin, HP-β-CD), polyvinylpyrrolidone (PVP K15 , PVP K17 , PVP K30 ), polylactic acid (PLA), polylactic acid-glycolic acid copolymer (PLGA), polyoxyethylene sorbitan fatty acid ester (TW20, TW80), polyethylene glycol (PEG 8000 , PEG 10000 , PEG 20000 The preparation method of P-AS is basically the same as that of Pluronic® F-127, except that Pluronic® F-127 is replaced by the above excipients.

[0061] Separately, a protein-based nanoformulation of astragaloside IV was prepared by preparing a protein solution: Albumin (BSA) and casein (CA) solutions were each dissolved in PBS at 20 mg / ml. A dimethyl sulfoxide (DMSO) solution of astragaloside IV was then added dropwise to the protein solution until the astragaloside IV concentration reached 6 mg / ml. The mixture was then sonicated using a transducer.

[0062] Each nanoparticle was placed at room temperature (25-27°C), and pictures were taken every 1 hour to analyze the aggregation of each nanoparticle. The results are shown in Figure 1. The arrows indicate that the nanoparticles began to aggregate and settle. Within 3 hours, the nanoparticles were K30 、PVP K17 、PVP K15 , TW20, TW80, HS-15, CO40, PLA, PLGA, EL, HP-β-CD, M-β-CD, PEG 8000 PEG 10000 and PEG 20000 Astragaloside nanoparticles prepared with Lip, Pluronic® F-127, CA and BSA as excipients have begun to aggregate and stratify, while astragaloside nanoparticles prepared with Lip, Pluronic® F-127, CA and BSA as excipients have no stratification within 24 hours, showing good stability.

[0063] The particle size, PDI, and potential of each nanoparticle formulation were measured using a Malvern laser particle size analyzer. As shown in Tables 1-3, the nanoparticles all had a particle size less than 1000 nm. Pluronic® F-127, phospholipids, albumin, and casein exhibited excellent performance and could be combined with astragaloside IV to produce water-soluble and stable astragaloside nanoparticle formulations. However, because the preparation of astragaloside nanoparticle formulations containing protein excipients requires a high amount of DMSO, an organic solvent that is difficult to remove, subsequent drug activity experiments were conducted on nanoparticle formulations prepared with the excipient Lip and Pluronic® F-127.

[0064] Among them, the nanoparticles made of Pluronic® F-127 and astragaloside IV have a particle size of approximately 260nm and a polydispersity index (PDI) of less than 0.3. The particle size distribution is relatively uniform, which has the best effect. Subsequent experimental studies have also proven that they are more effective against hepatitis B.

[0065] Table 1 Particle size, PDI and potential of astragaloside nanoparticle preparations

[0066] ExcipientsLipPluronic® F-127PVPK30PVPK17PVPK15TW20TW80Particle size(nm)96.67±14.64264.3±17.11242±9.41331.7±171.2218.1±67.33312.87±37.21127. 15±86.7PDI0.28±0.000.27±0.010.32±0.060.35±0.140.26±0.060.46±0.050.89±0.19Zeta potential (mV)-25.56±2.68-16.79±1.85-27.5±1.96-24.59±3.31-23.2±1.35-11.59±0.83-22.99±2.26

[0067] Table 2 Particle size, PDI and potential of astragaloside nanoparticle preparations

[0068] ExcipientsHS-15CO40PLAPLGABSACAParticle size (nm)905.33±157.46238.1±65.7679.43±118.01750.53±118.33285.13±53.3610.5±759.13PDI0.77±0.210.67±0.220.49±0.180.59±0.050.61±0.080.63±0.32Zeta potential (mV)-29.55±3.29-17.18±7.11-21.38±1.32-18.79±2.35-16.32±1.89-30.37±0.77

[0069] Table 3 Particle size, PDI and potential of astragaloside nanoparticle preparation

[0070] ELHP-β-CDM-β-CDPEG8000PEG10000PEG20000Particle size (nm)560.6±524.4263.87±15.30564.67±259.08252.83±39.47266.2±27.19211.7 3±48.76PDI0.67±0.160.36±0.130.51±0.230.38±0.040.38±0.130.37±0.04Zeta potential (mV)-9.38±1.19-29.72±0.56-15.12±2.81-21.92±11.1-23.41±1.04-26.26±2.47

[0071] (2) Characterization of nanoparticles

[0072] The morphology of astragaloside nanoparticles prepared with Pluronic® F-127 and astragaloside IV was observed using transmission electron microscopy. The method was as follows: a solution of astragaloside nanoparticles was mixed with a phosphomolybdic acid staining solution at a 1:1 volume ratio. The mixture was then added dropwise to the front of a copper mesh and allowed to stand in the dark for at least 2 hours. Excess water was then removed using filter paper and observed using a transmission electron microscope. As shown in Figure 2, the astragaloside nanoparticles were uniformly dispersed spheres, with a particle size of approximately 100-150 nm after dehydration.

[0073] Astragaloside IV (AS-IV), Pluronic® F-127, astragaloside nanoparticles (P-AS), and Pluronic® F-127 / AS-IV mixture (Mix) were analyzed by infrared spectroscopy to analyze the effects of drugs and excipients. -1 Scan the range and measure the infrared absorption peak of the sample. The results are shown in Figures 3 to 6: In the infrared spectrum of Astragaloside IV raw material, 3391.34 cm -1 The stretching vibration peak of -OH is at 1 092.96, 1 ​​066.03, and 1 044.70 cm -1 , which is the characteristic peak of polysaccharide hydroxyl group; 2877.24 cm of Pluronic® F-127 -1 is the stretching vibration peak of the C-H bond; the Pluronic® F-127 / AS-IV mixture has both characteristic peaks, while the astragaloside nanoparticles (P-AS) have a peak of 3391.34 cm -1 The peak at 400 nm was weakened, indicating that there was an interaction between AS-IV and Pluronic® F-127. Pluronic® F-127 was successfully loaded with AS-IV to obtain astragaloside nanoparticles (P-AS).

[0074] Example 2 Study on the anti-hepatitis B effect of different astragaloside nanoparticles

[0075] Experimental animals: C57 male mice, 7 weeks old, weighing about 20 g, and adaptively fed for 7 days.

[0076] On Day 0, AAV8 virus (1E+13 GC / ml) (100 μl / mouse) was injected into the tail vein. Blood was collected weekly for 6 weeks. Blood was collected from the orbital cavity (0.1 ml / mouse), centrifuged, and the supernatant was collected. Hepatitis B surface antigen (HBsAg) was detected using a Mindray CL-900i chemiluminescence analyzer.

[0077] At week 7, mice were randomly divided into a model group (Model group), a Pluronic® F-127 group (P group, i.e., Pluronic® F-127 alone, at a dose of 200 mg / kg), an astragaloside IV nanoparticle group (P-AS group, i.e., the preparation prepared with the excipients Pluronic® F-127 and astragaloside IV in Example 1, at a dose of 60 mg / kg), and an astragaloside IV liposome group (Lip-AS group, i.e., the preparation prepared with the excipients Lip and astragaloside IV in Example 1, at a dose of 60 mg / kg), with five animals per group. Intramuscular injections were administered daily, and blood samples were collected weekly for drug efficacy. As shown in Figure 7, there was no statistically significant difference between the Model group and the P group, while the Lip-AS group showed a trend toward lower HbsAg levels compared to the Model group. However, the HbsAg levels in the P-AS group were significantly lower than those in the Model group, P group, and Lip-AS group, with statistically significant differences. This suggests that the excipient Pluronic® F-127 alone has no significant effect on the HbsAg levels in animals, while the P-AS formulation can effectively lower the HbsAg levels, and the effect is better than that of the Lip-AS formulation.

[0078] Example 3 Study on the Anti-HBV Effect of Astragaloside Nanoparticles (P-AS) on High-Level HBV Infection

[0079] Experimental animals: C57 male mice, 7 weeks old, weighing about 20 g, and adaptively fed for 7 days.

[0080] D0: AAV8 virus (1E+13 GC / ml) 100 μl / mouse was injected into the tail vein, and blood was collected once a week for 6 weeks.

[0081] At week 7, based on the results, the mice were randomly divided into a model group and a P-AS group (the preparation prepared with the excipients Pluronic® F-127 and astragaloside IV in Example 1), with six animals per group. P-AS (astragaloside IV dosage: 60 mg / kg; excipient dosage: 200 mg / kg) was administered intramuscularly daily, and blood samples were collected weekly for drug efficacy. The results are shown in Figure 8, where the abscissa represents time. After modeling, hepatitis B surface antigen (HBsAg) levels in both the Model and P-AS groups reached over 15,000 IU / ml. After one and two weeks of dosing, HBsAg levels in the P-AS group decreased significantly, with statistically significant differences compared to the Model group. While currently used hepatitis B treatments are difficult to eliminate from the body, the P-AS preparation prepared with the excipients Pluronic® F-127 and astragaloside IV in this example can effectively reduce HBsAg levels, providing a promising candidate for hepatitis B treatment.

[0082] Example 4 Safety Study of Astragaloside Nanoparticles (P-AS)

[0083] Experimental animals: C57 male mice, 7 weeks old, weighing about 20 g, and adaptively fed for 7 days.

[0084] P-AS, prepared from the excipient Pluronic® F-127 and astragaloside IV described in Example 1, was administered intramuscularly once daily (astragaloside IV dosage: 60 mg / kg; excipient dosage: 200 mg / kg). Body weight was recorded daily. The body weight curve is shown in Figure 9. The data demonstrates that the animals' body weights remained relatively stable during the dosing period, indicating that the astragaloside nanoparticles are relatively safe for animals.

[0085] The above are merely optional embodiments of the present application and are not intended to limit the present application. For those skilled in the art, the present application may have various modifications and variations. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present application should be included within the scope of the claims of the present application.

Claims

1. A nano-preparation of astragaloside IV for treating hepatitis B, characterized in that: include: Astragaloside IV and auxiliary materials, wherein the auxiliary materials include at least one of polyoxyethylene polyoxypropylene ether triblock copolymer, phospholipid, albumin and casein.

2. The astragaloside nanoparticle preparation according to claim 1, wherein The mass ratio of the astragaloside IV to the auxiliary material is 1:(1-4).

3. The astragaloside nanoparticle preparation according to claim 1, wherein The astragaloside nano preparation includes a nanoparticle preparation.

4. The astragaloside nanoparticle preparation according to claim 3, wherein The average particle size of the astragaloside nano preparation is less than or equal to 700 nm, and the polydispersity index is less than or equal to 0.

3.

5. The astragaloside nanoparticle preparation according to any one of claims 1 to 4, characterized in that The auxiliary material is a polyoxyethylene polyoxypropylene ether triblock copolymer, and the average particle size of the astragaloside nano preparation is 60-600 nm, and the polydispersity index is 0.25-0.

30.

6. A method for preparing the astragaloside nanoformulation according to any one of claims 1 to 5, characterized in that: include: The astragaloside IV and the auxiliary materials are mixed and then subjected to thin film hydration treatment to obtain the astragaloside IV nano preparation.

7. The method for preparing the astragaloside nanoformulation according to claim 6, wherein: The step of mixing the astragaloside IV and the auxiliary materials and then subjecting them to a thin film hydration treatment comprises: The astragaloside IV and the auxiliary materials are dissolved in an organic solvent, and then the solvent is removed by rotary evaporation to form a film; the film is mixed with a glucose aqueous solution for hydration treatment, and then ultrasonically dispersed.

8. The method for preparing the astragaloside nanoformulation according to claim 7, wherein: The organic solvent includes an alcohol solvent.

9. The method for preparing the astragaloside nanoformulation according to claim 7, wherein: The mass fraction of glucose in the glucose aqueous solution is 4-6%.

10. The method for preparing the astragaloside nanoformulation according to any one of claims 7 to 9, characterized in that: The volume ratio of the mass of the astragaloside IV to the glucose aqueous solution is 1 mg: 0.1-0.2 mL.

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