Plumbagin amorphous solid dispersion as well as preparation method and application thereof

Abstract

The invention discloses a plumbagin amorphous solid dispersion as well as a preparation method and application thereof. The plumbagin amorphous solid dispersion is prepared from the following raw materials: plumbagin, a high-molecular polymer and a solvent. The preparation method comprises the following step: treating a mixed system containing plumbagin, a high-molecular polymer and a solvent through an electrostatic spraying technology to obtain the plumbagin amorphous solid dispersion. The plumbagin amorphous solid dispersion provided by the invention has relatively high solubility, relatively high dissolution speed and relatively high oral bioavailability, and can effectively solve the problem that the oral bioavailability is limited by low solubility of plumbagin.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and particularly relates to a plumbaginone amorphous solid dispersion and a preparation method and application thereof. Background Art

[0002] Plumbagin is a natural compound that can be used to treat liver fibrosis. The chemical name of plumbagin is benzothiophene-2,3-one, and its chemical formula is C 11 H8O3, molecular weight is 188.18. The chemical structure is as follows:

[0003]

[0004] Plumbagin belongs to BCS II in the biopharmaceutics classification system, and has the characteristics of low solubility and high permeability. Low solubility is the limiting step affecting its oral bioavailability. Therefore, improving the solubility and dissolution rate of plumbagin, and then improving the oral bioavailability of the drug, is the key to developing a formulation with excellent performance.

[0005] In recent years, various injectable formulations of plumbagin have been developed at home and abroad, such as lyophilized liposomes, thermosensitive liposomes, polyethylene glycol long-circulating liposomes, chitosan microspheres, and isoniazid-β-cyclodextrin inclusion complexes, which are mainly used to enhance the anti-cancer efficacy of tumor cells such as osteosarcoma, melanoma, breast cancer, and prostate cancer. Patent CN1 17298046A uses amphiphilic graft copolymers as carriers to prepare plumbagin nano-micelles for the treatment of melanoma. Patent CN115282126A uses a mannose-modified plumbagin nanostructured lipid carrier to treat pulmonary fibrosis. However, existing studies and patents rarely report on plumbagin oral preparations. This is because plumbagin is a small molecule compound of the naphthoquinone class, which has the disadvantages of poor water solubility, short biological half-life, low bioavailability, and high cytotoxicity, which greatly limits its clinical application.

[0006] Electrostatic spray technology (Electrospray) can effectively improve the drug dissolution rate. Patent CN107802601A uses electrostatic spray technology to prepare pure poorly soluble drug nanoparticles (crystals) of different particle sizes, which can improve the water solubility of poorly soluble drugs and improve bioavailability; Patent CN109432021A uses coaxial electrostatic spray technology and double-layer nanostructure as the drug release system, and improves the solubility of astaxanthin and the in vivo and in vitro drug release through the solubilization, stabilization and absorption promotion of hydrophilic polymer carriers and absorption-promoting components; However, coaxial electrostatic spray technology uses more materials, and the hydrophilic polymer carriers used are polyvidone (PVP) and polyethylene glycol (PEG), which can only interact with polar APIs.

[0007] At present, there are few reports on the technology of preparing plumbagin using electrostatic spray technology. How to use electrostatic spray technology to prepare plumbagin with better solubility, thereby improving the oral bioavailability of plumbagin, is one of the problems that need to be solved urgently. Summary of the invention

[0008] The main purpose of the present invention is to provide a plumbaginone amorphous solid dispersion and a preparation method and application thereof, so as to overcome the shortcomings of the prior art.

[0009] In order to achieve the above-mentioned invention object, the technical solution adopted by the present invention includes:

[0010] One aspect of the present invention provides a plumbagin amorphous solid dispersion. The raw materials for preparing the plumbagin amorphous solid dispersion include plumbagin, a high molecular polymer and a solvent.

[0011] Another aspect of the present invention provides an aqueous solution of an amorphous solid dispersion of plumbagin, comprising the amorphous solid dispersion of plumbagin and water.

[0012] Another aspect of the present invention also provides a method for preparing the plumbagin amorphous solid dispersion, which comprises: subjecting a mixed system comprising plumbagin, a high molecular polymer and a solvent to electrostatic spraying technology to obtain the plumbagin amorphous solid dispersion.

[0013] Another aspect of the present invention also provides the use of the plumbaginone amorphous solid dispersion in the preparation of oral drugs.

[0014] Compared with the prior art, the present invention has at least the following beneficial effects:

[0015] (1) The plumbagin amorphous solid dispersion provided by the present invention has high solubility and dissolution rate, thus solving the problem that the low solubility of plumbagin limits oral bioavailability.

[0016] (2) The present invention provides an amorphous solid dispersion (ASD) formed by electrospraying using electrostatic spraying technology, with a narrower particle size distribution, thereby generating a higher specific surface area, thereby further improving the drug dissolution rate. At the same time, the amorphous API in the ASD is easy to dissolve without destroying its crystal lattice, so that it can dissolve faster and form a supersaturated drug solution when exposed to water.

[0017] (3) The polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus) of the present invention is an amphiphilic polymer that can dissolve hydrophobic APIs in water, thereby further improving solubility; and the amphiphilicity of Soluplus enables it to form complexes with polar and non-polar APIs, and plumbagin is released very quickly in the body, thereby increasing bioavailability.

[0018] (4) The electrostatic spraying technology used in the present invention is simple and suitable for industrialization. The mixed system uses less materials than coaxial electrostatic spraying, while reducing the possible cytotoxicity. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0020] Figure 1 is an X-ray diffraction pattern of the plumbaginone amorphous solid dispersion (PBG-ASD) powder prepared in Example 1 of the present invention;

[0021] Figure 2 is the X-ray diffraction pattern of plumbaginone (PBG) raw material medicine of Comparative Example 1 of the present invention;

[0022] Figure 3 is a DSC graph of the PBG-ASD powder prepared in Example 1 of the present invention;

[0023] Figure 4 It is a DSC comparison chart of the PBG bulk drug of Comparative Example 1 of the present invention;

[0024] Figure 5 FTIR images of the PBG-ASD powder prepared in Example 1 of the present invention and the PBG bulk drug of Comparative Example 1;

[0025] Figure 6 This is a SEM image of the PBG-ASD powder prepared in Example 1 of the present invention;

[0026] Figure 7 The in vitro dissolution curves of the PBG-ASD powder prepared in Example 1 of the present invention, the PBG API of Comparative Example 1, and the PBG API and Soluplus mixture (PM) of Comparative Example 2 are shown;

[0027] Figure 8The drug-time curves of the PBG-ASD powder prepared in Example 1 of the present invention and the PBG bulk drug of Comparative Example 1 are shown. DETAILED DESCRIPTION

[0028] In view of the problems existing in the above-mentioned prior art, the inventors of the present invention have conducted extensive and in-depth research and provided a plumbagin amorphous solid dispersion, which mainly adopts raw materials such as plumbagin, high molecular polymer, solvent and combines with electrostatic spraying technology to further improve the solubility and bioavailability of the plumbagin amorphous solid dispersion.

[0029] The technical solution, its implementation process and principle will be further explained as follows.

[0030] As one aspect of the technical solution of the present invention, a plumbagin amorphous solid dispersion is provided. The raw materials for preparing the plumbagin amorphous solid dispersion include plumbagin, a high molecular polymer, and a solvent.

[0031] In some embodiments, the plumbagin amorphous solid dispersion is spherical, and the particle size is 1.89±0.16 μm.

[0032] In some embodiments, the weight ratio of plumbaginone to high molecular weight polymer is 1:2-20.

[0033] In some preferred embodiments, the weight ratio of plumbaginone to high molecular weight polymer is 1:5-10.

[0034] In some embodiments, the weight ratio of the high molecular weight polymer to the solvent is 2-20:100.

[0035] In some preferred embodiments, the weight ratio of the high molecular weight polymer to the solvent is 5-10:100.

[0036] In some embodiments, the high molecular weight polymer includes any one or a combination of two or more of hydroxypropyl methylcellulose acetate succinate (HPMCAS), hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol (PVA), polyvinyl pyrrolidone (VA64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus), etc., but is not limited thereto.

[0037] In some preferred embodiments, the high molecular weight polymer includes a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer based on the thermal stability of the polymer. Soluplus is a polyvinyl alcohol caprolactam-polyvinyl alcohol-polyvinyl acetate graft copolymer developed by BASF as a dedicated stabilizer; and Soluplus is an amphiphilic polymer excipient that can interact with hydrophobic APIs while still being easily soluble in water, which helps to form a complex with plumbagin. And plumbagin is released very quickly in the body, which can effectively increase bioavailability.

[0038] In some embodiments, the solvent includes at least any one of methanol, acetonitrile, dichloromethane, water, etc., but is not limited thereto.

[0039] In some preferred embodiments, the solvent comprises methanol.

[0040] As another aspect of the technical solution of the present invention, a plumbagin amorphous solid dispersion aqueous solution is provided, comprising the plumbagin amorphous solid dispersion and water.

[0041] In some embodiments, the amorphous solid dispersion of plumbagin in the aqueous solution of amorphous solid dispersion of plumbagin is in a micellar state.

[0042] In some embodiments, the mass ratio of the plumbaginone amorphous solid dispersion to water is 1:1-1:22.

[0043] In some embodiments, the particle size of the amorphous solid dispersion of plumbagin in the aqueous solution of amorphous solid dispersion of plumbagin is 553.80±0.2 nm.

[0044] As another aspect of the technical solution of the present invention, the preparation method of the plumbagin amorphous solid dispersion provided therein comprises: subjecting a mixed system comprising plumbagin, a high molecular polymer and a solvent to electrostatic spraying technology to obtain the plumbagin amorphous solid dispersion.

[0045] Electrostatic spray technology (Electrospray) is to dissolve drugs and polymer materials to form a uniform solution, load it into a micro-propeller, and use a high-voltage electrostatic field to atomize drug-containing droplets under the combined action of electrostatic field force and external force to form a cone-shaped radiation-containing spray. As the solvent evaporates during the directional movement toward the receiving device, it eventually forms drug-containing micro- and nanoparticles with diameters between nanometers and micrometers and forms an amorphous solid dispersion, thereby increasing the drug dissolution rate.

[0046] The use of raw materials such as plumbagin, high molecular polymers, solvents and electrostatic spraying technology can further improve the dissolution and bioavailability of plumbagin amorphous solid dispersion. Through electrospraying, hydrogen bonds are formed between plumbagin and Soluplus to form ASD, and the resulting ASD particles have a narrower size distribution, thereby producing a higher specific surface area, thereby further improving the drug dissolution rate. At the same time, the amorphous API in the ASD is easy to dissolve without destroying its lattice, allowing faster dissolution and forming a supersaturated drug solution when exposed to water.

[0047] In some embodiments, the plumbagin amorphous solid dispersion is prepared by spraying the mixed system using an electrostatic spraying technique.

[0048] In some embodiments, the spray temperature of the electrostatic spray technology is 20°C-30°C.

[0049] In some preferred embodiments, the spraying temperature of the electrostatic spraying technology is 20°C-25°C.

[0050] In some embodiments, the electrostatic spray technique has a spray humidity of 30%-80%.

[0051] In some preferred embodiments, the spray humidity of the electrostatic spray technology is 30%-60%.

[0052] In some embodiments, the electrostatic spray technique has a flow rate of 0.5 mL / h-1 mL / h.

[0053] In some embodiments, the voltage of the electrostatic spray technique is 8.20 kV-8.90 kV.

[0054] As another aspect of the technical solution of the present invention, it provides the use of the plumbaginone amorphous solid dispersion in the preparation of oral drugs.

[0055] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with embodiment. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. Those skilled in the art can make modifications or equivalent substitutions based on the understanding of the technical scheme of the present invention without departing from the spirit and scope of the technical scheme of the present invention, and all should be included in the protection scope of the present invention.

[0056] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in the field can be used. If no manufacturer is specified for the reagents or instruments used, they can be obtained commercially and do not involve the core technical means of the present invention.

[0057] The detection instrument and instrument parameter settings used in the embodiment of the present invention are as follows:

[0058] (1) Powder X-ray diffraction

[0059] Instrument: Bruker D8 Advance X-ray Diffractometer

[0060] Target: Cu-Kα target

[0061] wavelength:

[0062] Tube voltage: 40kV

[0063] Tube current: 40mA

[0064] Step size: 0.02°

[0065] Scanning speed: 4° / min

[0066] Scanning range: 5°-40°

[0067] (2) Differential Scanning Calorimetry (DSC)

[0068] Instrument: DSC 2500 differential scanning calorimeter

[0069] Heating rate: 10℃ / min

[0070] Temperature range: 30-800℃

[0071] (3) Fourier transform infrared spectroscopy (FT-IR)

[0072] Instrument: Nicolet iS50 infrared spectrometer

[0073] Wavelength: 400-4000cm- 1

[0074] Resolution: 4cm- 1

[0075] (4) Scanning electron microscopy (SEM)

[0076] Instrument: Regulus 8230 scanning electron microscope

[0077] Voltage: 10kV

[0078] (5) High performance liquid chromatography (HPLC)

[0079] Instrument: Wanyi HPLC detector

[0080] Chromatographic column: Unitary C18 column (4.6mm×250mm, 5μm)

[0081] Mobile phase: methanol: water ratio 20:80

[0082] Flow rate: 1.0 ml min -1

[0083] Column temperature: 30°C

[0084] Detection wavelength: 254nm

[0085] Injection volume: 10 μL

[0086] Example 1

[0087] 1 part by mass of plumbaginone, 10 parts by mass of Soluplus, and 100 parts by mass of methanol were uniformly mixed to obtain a mixture;

[0088] The obtained mixture is sprayed using an electrostatic sprayer, wherein the temperature of the electrostatic spray is 22°C-24°C, the spraying speed is 0.5 mL / h, the spraying humidity is 40%-60%, and the spraying voltage is 8.20 kV to obtain an electrostatic spray product;

[0089] The product of the electrostatic spraying is scraped off to obtain a plumbaginone amorphous solid dispersion.

[0090] Embodiment 2-10

[0091] The only difference between Example 2-10 and Example 1 is that the composition of the mixture, the component content and the electrostatic spraying conditions are changed as shown in Table 1, and the rest is implemented in the same way as Example 1. The mixture composition, component content and electrostatic spraying conditions of Example 2-10 are shown in Table 1.

[0092] Table 1 Electrostatic spray raw material composition and electrostatic spray conditions of Examples 1-10

[0093]

[0094]

[0095] Table 1 shows the raw material composition and process parameters of the preparation method for preparing the plumbagin amorphous solid dispersion in Examples 1-10.

[0096] Comparative Example 1

[0097] PBG API is used.

[0098] Comparative Example 2

[0099] PBG API and Soluplus mixture (PM) were used.

[0100] The present invention tested the plumbagin amorphous solid dispersion according to Example 1 of the present invention, the PBG bulk drug of Comparative Example 1, and the PM of Comparative Example 2, as follows:

[0101] 1. X-ray diffraction

[0102] Figure 1 is the X-ray diffraction pattern of the PBG-ASD powder prepared in Example 1 of the present invention, Figure 2 is the X-ray diffraction pattern of PBG API, Figure 2 In comparison, the characteristic peak of the PBG bulk drug disappeared, indicating that the amorphous solid dispersion was successfully prepared in Example 1.

[0103] 2.DSC detection

[0104] Figure 3 is the DSC graph of the PBG-ASD powder prepared in Example 1 of the present invention, Figure 4 is the DSC diagram of PBG raw material, and Figure 4 In comparison, the melting peak of PBG API at 76.91°C disappeared, indicating that plumbagin was dispersed in the polymer carrier in an amorphous state.

[0105] 3. FT-IR detection

[0106] Figure 5 FTIR test results of PBG-ASD powder and PBG API prepared in Example 1 of the present invention. Figure 5 As shown, the PBG-ASD prepared by the present invention is compared with the PBG raw material, and the PBG raw material is located at 1609cm- 1 The benzene ring stretching vibration peak is masked, and PBG-ASD increases the Soluplus peak at 3457cm- 1 The NH stretching vibration peak and the CH3 and CH2 vibration absorption peaks at 2925 and 2856 cm-1.

[0107] 4. SEM inspection

[0108] Figure 6 : is a SEM test result diagram of the PBG-ASD powder prepared in Example 1 of the present invention. Figure 6 As shown, the PBG-ASD prepared by the present invention has a smooth and full surface, a uniform size distribution, and a particle size of 1.89±0.16 μm.

[0109] 5. In vitro dissolution test

[0110] The present invention conducts an in vitro dissolution test on the dissolution of the PBG-ASD powder prepared in Example 1 in aqueous solution. Take the sample of Example 1 in Table 1, set the speed to 100 rpm in the aqueous dissolution medium, and operate according to the dissolution and release determination method. After 15, 30, 45, 60, 90, 120, 180, and 240 minutes, take an appropriate amount of the dissolution solution, filter it, take the subsequent filtrate as the test solution, and determine it by HPLC. The determination results are shown in Table 2 and Figure 7 .

[0111] Table 2. Average cumulative dissolution test results of Example 1 (n=3)

[0112]

[0113] 6. Comparative study on the pharmacokinetics of plumbagin amorphous solid dispersion and plumbagin API under fasting conditions

[0114] Model animal screening and grouping: Six Wistar rats (200-300 g) were randomly divided into groups A and B according to a random coding table, with 3 rats in each group, and placed in breeding cages with 3 rats in each cage.

[0115] Drug preparation: Within 1 hour before administration, the PBG-ASD drug powder and plumbagin raw material drug in Example 1 of the present invention were dissolved in physiological saline solution at a rate of 5 mg / kg, and stored after being vortexed thoroughly.

[0116] Drug administration: Rats were allowed free access to water and fasted for 12 hours. They were marked and given 5 mg / kg of the drug by gavage according to a random table.

[0117] Blood samples and blood collection: About 0.5 mL of venous blood was drawn from rats before medication (i.e., 0 h, within 60 min before medication) and 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, and 24 h after medication, and placed in sodium heparin anticoagulant tubes. A total of 12 tubes of venous blood were collected in each cycle. The blood collection table must clearly record the actual blood collection time, accurate to seconds, and the blood collection time window range is shown in Table 3.

[0118] Table 3. Fasting blood collection point and blood collection time window requirements

[0119] Blood collection point Blood collection time window 0h -Within 60 minutes 0.25-6h (including 6h) ±2min 6h-24h (including 24h) ±3min

[0120] Blood sample processing: Blood samples are collected into labeled vacuum blood collection tubes containing sodium heparin anticoagulant that have been precooled in an ice water bath in advance, and immediately placed in an ice water bath. After blood sample collection, it is transferred to the sample processing room for centrifugation. After centrifugation, the plasma is divided into test samples and backup samples. After division, it is first transferred to a 20°C refrigerator for temporary storage. The blood sample should be controlled within 2 hours from the time of separation to the time of storage in a 20°C refrigerator. The samples are divided into test samples and backup samples for cryopreservation based on the time point.

[0121] Blood sample drug concentration detection: Plasma samples were collected from subjects at different time points after taking the drug, and the drug concentration of plumbagin in plasma was detected by high performance liquid chromatography (HPLC). The biological sample analysis methodology validation and clinical trial sample testing were carried out in accordance with the "Technical Guidelines for Clinical Pharmacokinetic Studies of Chemical Drugs (NMPA, No. [H] GCL1-2)", "Guidelines for Validation of Biological Sample Analysis Methods (Pharmacopoeia 2015 Edition)" and other relevant guidelines.

[0122] Calculation of pharmacokinetic parameters: The main pharmacokinetic parameters are: the area under the drug concentration-time curve (AUC) from time 0 to the last sample collection time t at which the concentration can be accurately measured 0-t ), the area under the drug concentration-time curve (AUC 0-∞ ), the peak concentration of the drug (C max ), other indicators include: elimination half-life (t 1 / 2β ), peak time of drug action (T max ) Pharmacokinetic (PK) parameters are calculated by collecting blood sample data at predetermined time points and performing PK analysis using a non-compartmental model.

[0123] The above rat pharmacokinetic study data: The peak time of blood drug concentration of plumbagin amorphous solid dispersion in rats after oral administration is T max The average time is 1 hour, and the peak concentration C max The average was 119.72 μg / mL, AUC0 -∞ The average is 367.14 μg·h / mL; while. The peak time of blood drug concentration of plumbaginone in rats after oral administration is T max The average time is 2 hours, and the peak concentration C max The average was 26.04 μg / mL, AUC 0-∞ The average is 60.99 μg·h / mL. The above data show that the plumbagin amorphous solid dispersion of the present invention has a higher peak concentration after oral administration on an empty stomach, better drug plasma exposure, and higher in vivo bioavailability. Therefore, the plumbagin amorphous solid dispersion of the present invention has a more obvious oral bioavailability advantage and better efficacy. Figure 8It is the drug-time curve of plumbagin amorphous solid dispersion and plumbagin API. Figure 8 It can be seen that the plumbagin amorphous solid dispersion of the present invention is superior to the plumbagin API when taken orally on an empty stomach. Compared with the plumbagin API, the plumbagin amorphous solid dispersion of Example 1 has an in vitro dissolution rate of 18.8 times higher at 240 min, a maximum blood drug concentration of 4.60 times higher, and a bioavailability of 6.02 times higher.

[0124] The various aspects, embodiments, features and examples of the present invention should be considered as illustrative in all aspects and are not intended to limit the present invention, the scope of the present invention is defined only by the claims. Other embodiments, modifications and uses will be apparent to those skilled in the art without departing from the spirit and scope of the claimed invention.

[0125] In addition, the inventors of this case also referred to the aforementioned embodiments and conducted experiments with other raw materials, process operations, and process conditions described in this specification, and obtained relatively ideal results.

[0126] Although the present invention has been described with reference to illustrative embodiments, it will be appreciated by those skilled in the art that various other changes, omissions and / or additions may be made without departing from the spirit and scope of the present invention and that the elements of the embodiments may be replaced by substantial equivalents. In addition, many modifications may be made without departing from the scope of the present invention to adapt specific circumstances or materials to the teachings of the present invention. Therefore, it is not intended herein to limit the present invention to the disclosed specific embodiments for performing the present invention, but it is intended that the present invention will include all embodiments within the scope of the appended claims. In addition, unless specifically stated, any use of the terms first, second, etc. does not indicate any order or importance, but rather uses the terms first, second, etc. to distinguish one element from another.

Claims

1. A plumbaginone amorphous solid dispersion, characterized in that: The raw materials for preparing the plumbagin amorphous solid dispersion include plumbagin, a high molecular polymer and a solvent.

2. The plumbaginone amorphous solid dispersion according to claim 1, characterized in that: The plumbaginone amorphous solid dispersion is spherical, with a particle size of 1.89±0.16 μm; And / or, the mass ratio of plumbaginone to the high molecular polymer is 1:2-20; And / or, the mass ratio of the high molecular polymer to the solvent is 2-20:100; And / or, the high molecular polymer includes any one or a combination of two or more of hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, polyvinyl alcohol, polyvinyl pyrrolidone, and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; And / or, the solvent includes at least any one of methanol, acetonitrile, dichloromethane and water.

3. The plumbaginone amorphous solid dispersion according to claim 2, characterized in that: The mass ratio of plumbaginone to the high molecular polymer is 1:5-10; And / or, the mass ratio of the high molecular polymer to the solvent is 5-10:100; And / or, the high molecular polymer includes polyethylene caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; And / or, the solvent comprises methanol.

4. An aqueous solution of an amorphous solid dispersion of plumbaginone, characterized in that: The aqueous solution of the plumbagin amorphous solid dispersion comprises the plumbagin amorphous solid dispersion according to any one of claims 1 to 3 and water.

5. The plumbaginone amorphous solid dispersion according to claim 4, characterized in that: The plumbagin amorphous solid dispersion is in a micellar state in the plumbagin amorphous solid dispersion aqueous solution; And / or, the mass ratio of the plumbaginone amorphous solid dispersion to water is 1:1-1:22; And / or, the particle size of the plumbagin amorphous solid dispersion in the plumbagin amorphous solid dispersion aqueous solution is 553.80±0.2 nm.

6. The method for preparing the plumbaginone amorphous solid dispersion according to any one of claims 1 to 3, characterized in that: The mixed system containing plumbagin, high molecular polymer and solvent is treated by electrostatic spraying technology to obtain the plumbagin amorphous solid dispersion.

7. The preparation method according to claim 6, characterized in that: include: The plumbaginone amorphous solid dispersion is prepared by spraying the mixed system through electrostatic spraying technology.

8. The preparation method according to claim 7, characterized in that: The spray temperature of the electrostatic spray technology is 20°C-30°C; And / or, the spray humidity of the electrostatic spray technology is 30%-80%; and / or, the flow rate of the electrostatic spray technology is 0.5 mL / h-1 mL / h; And / or, the voltage of the electrostatic spraying technology is 8.20kV-8.90kV.

9. The preparation method according to claim 8, characterized in that: The spray temperature of the electrostatic spray technology is 20°C-25°C; And / or, the spray humidity of the electrostatic spray technology is 30%-60%.

10. Use of the plumbaginone amorphous solid dispersion according to any one of claims 1 to 3 in the preparation of oral medicines.

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