NANO abiraterone acetate composition, preparation method therefor, and oral preparation thereof

Abstract

A nano abiraterone acetate composition, a preparation method therefor, and an oral tablet thereof. The composition comprises abiraterone acetate, a suspending aid, a surfactant, and a stabilizer in percentage by weight of 1:(0.1-4):(6-20):(0.01-0.1), and is prepared by wet grinding, drying, and dewatering. The oral bioavailability of the product is improved by adding a cholate absorption-promoting agent, such that the influence of food on drug absorption is reduced.

Description

A nanometer abiraterone acetate composition, preparation method thereof, and oral preparation Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, and in particular to a nanometer abiraterone acetate composition, a preparation method thereof, and an oral preparation thereof. Background Art

[0002] Abiraterone acetate tablets, chemically named 17-(3-pyridyl)androstane-5,16-dien-3-β-ol, are a CYP17 inhibitor developed by Johnson & Johnson. They were first approved by the US Food and Drug Administration (FDA) in 2011 under the trade name Zytiga, used in combination with prednisone for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Abiraterone acetate was subsequently launched in multiple global markets, including China (trade name Zytiga), the European Union, and Japan.

[0003] After entering the human body, abiraterone acetate is converted into the biologically active form of abiraterone through deacetylation. Abiraterone acetate is a lipophilic compound with high solubility in organic solvents but virtually insoluble in water and poor permeability. It belongs to BCS Class 4, with a bioavailability of less than 10%. Therefore, the dosage is 1000 mg (250 mg / tablet x 4 tablets). Abiraterone acetate also has a significant food effect: patients are required to take the drug on an empty stomach, maintaining this fast for not only 2 hours before but also 1 hour after taking the drug. These issues indicate that this product presents safety risks: hepatotoxicity, food effects, individual variability, and a relatively high daily dose (1000 mg). Improving the drug's bioavailability and individual variability through formulation is currently a priority for pharmaceutical manufacturers.

[0004] Patent CN106687112A discloses an improved abiraterone acetate formulation. By controlling the particle size of the API, abiraterone acetate, a unit dosage form is produced. A 500mg unit dosage form is bioequivalent to a 1000mg dose of Zytiga in healthy male subjects in the fasting state, indicating a 1000mg increase in bioavailability. Although the formulation's dose is reduced by 500mg, it does not increase abiraterone acetate's permeability to gastrointestinal epithelial cells, resulting in a low oral bioavailability.

[0005] Patent CN103446069A discloses an oral solid composition of abiraterone and a preparation method thereof. The abiraterone acetate API is micronized and the particle size is controlled within the range of 0-20 μm to improve the tablet dissolution rate. However, research has found that micronization of the API alone does not significantly improve dissolution, and special equipment is required to crush it to this particle size range.

[0006] Patent CN103070828A discloses a solid dispersion and tablet containing abiraterone acetate, as well as a preparation method thereof. The solid dispersion is prepared by dissolving abiraterone acetate and povidone in chloroform at a ratio of 1:0.5-4, drying under reduced pressure, then grinding in water, granulating, and drying. Although this patent improves dissolution, the process requires the preparation of a solid dispersion and the use of the solvent chloroform, negating safety concerns and worker protection. Furthermore, the dissolution improvement is limited, with a 64% dissolution rate achieved in 10 minutes in a surfactant-added medium at pH 4.5, resulting in low bioavailability.

[0007] In summary, abiraterone acetate has the characteristics of poor solubility and low osmotic pressure. Although the oral bioavailability of abiraterone acetate can be improved and the effect of food can be eliminated by dissolving abiraterone acetate in a solvent to prepare liquid capsules, the solvents in the liquid capsules, such as propylene glycol or ethanol, are volatile and may cause abiraterone to precipitate during long-term storage; too much surfactant, such as Tween 80 and Span 80, will increase the liver burden and cause allergies in some people.

[0008] Summary of the Invention

[0009] In order to overcome the deficiencies of the prior art, the present invention provides a nano-abiraterone acetate composition, which has a small particle size of abiraterone acetate, can significantly improve the bioavailability of abiraterone acetate, and promote rapid absorption of the drug in the body.

[0010] The second aspect of the present invention provides a method for preparing a nano-abiraterone acetate composition, which has a simple process and requires little equipment investment.

[0011] The third aspect of the present invention provides an oral preparation comprising a nano-abiraterone acetate composition, which significantly improves the bioavailability of abiraterone acetate and promotes rapid absorption of the drug in the body.

[0012] Specifically, the present invention is achieved by the following method:

[0013] According to a first aspect of the present invention, a nano-abiraterone acetate composition is provided, which comprises abiraterone acetate, a suspending agent, a surfactant and a stabilizer in a weight percentage of 1: (0.1-4): (6-20): (0.01-0.1).

[0014] Furthermore, in the nano-abiraterone acetate composition, the weight percentages of abiraterone acetate, suspending agent, surfactant and stabilizer are 1:(0.2-0.6):(10-15):(0.02-0.05).

[0015] Furthermore, in the nano-abiraterone acetate composition, D90 of abiraterone acetate is ≤450 nm. Preferably, D90 of abiraterone acetate is ≤400 nm, for example, it can be one of the following values: 400 nm, 380 nm, 343 nm, 350 nm, 300 nm.

[0016] In the present invention, D90 represents the particle size corresponding to when the cumulative particle size distribution number of the sample reaches 90%; when D90≤450nm, it means that the particles with a particle size of less than or equal to 450nm account for 90%.

[0017] Furthermore, in the composition, the polymer dispersibility index PDI of the abiraterone acetate is ≤0.5, for example, it may be 0.444, 0.372, 0.154, 0.146, 0.25, 0.35, etc.

[0018] Further, in the composition, the suspending agent includes one or any combination of caprylic acid capric acid mono- and diglycerides, polyglycol glycerides, hydroxypropyl cellulose, poloxamer, vinyl pyrrolidone / vinyl acetate copolymer, polyethylene glycol, poly(2-ethyl-2-oxazoline), polyvinyl pyrrolidone, block copolymers based on ethylene oxide and propylene oxide, poly(maleic acid / methyl vinyl ether) copolymer, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, polyethylene glycol 15 hydroxystearate, ethylene oxide / propylene oxide block copolymer, polyvinyl alcohol-polyethylene glycol graft copolymer, d-α-tocopheryl polyethylene glycol 1000 succinate and copovidone VA64; preferably, the suspending agent is copovidone VA64.

[0019] Furthermore, in the composition, the surfactant includes one or any combination of polyoxyethylene ether, poloxamer, sodium dodecylbenzene sulfonate, sodium lauryl sulfate, lecithin, Tween 80, Span 80, docusate sodium and polyethoxylated hydrogenated castor oil; preferably, the surfactant is sodium lauryl sulfate.

[0020] Furthermore, in the composition, the stabilizer includes one or any combination of sodium sulfite, sodium metabisulfite, sodium bisulfite, sodium thiosulfate, dibutylphenol, vitamin C, gallic acid ester, α-tocopherol, butylated hydroxyanisole, ascorbyl palmitate, tert-butylated hydroxyanisole, 2,6-di-tert-butylated hydroxytoluene and tert-butylated hydroquinone; the stabilizer is preferably butylated hydroxyanisole; preferably, the stabilizer is butylated hydroxyanisole.

[0021] On the other hand, the present invention provides a method for preparing the above-mentioned nano-abiraterone acetate composition, comprising the following steps: preparing a suspension by wet grinding abiraterone acetate, a suspending agent, a surfactant and a stabilizer according to weight percentages, and drying and removing water from the suspension to obtain the nano-abiraterone acetate composition.

[0022] Furthermore, the preparation method of the nano-abiraterone acetate composition comprises the following steps: preparing a suspension by wet grinding abiraterone acetate, a suspending agent, a surfactant and a stabilizer according to weight percentage, and freeze-drying the suspension under reduced pressure to obtain the nano-abiraterone acetate composition.

[0023] Furthermore, the suspension is freeze-dried at -50°C for 20-35h to obtain a nano-abiraterone acetate composition.

[0024] Furthermore, during wet grinding, the type of grinding machine can be a bead mill, a planetary grinder, a roller mill, etc. The grinding body is preferably a zirconia grinding bead, and the diameter of the grinding bead can be 0.5-10 mm, preferably 0.5-1 mm, and more preferably a YTZ zirconia grinding bead with a diameter of 0.65 mm. The grinding time and speed need to be pre-set to ensure that the abiraterone acetate nano-mixture is obtained. The grinding speed is preferably 1500-3500 rpm, more preferably 2000-3000 rpm; the grinding time is preferably 5 minutes to 30 hours, and can be selected from the following time periods: 5 minutes to 30 minutes, 10 minutes to 30 minutes, 1 hour to 5 hours, 8 hours to 15 hours, and 9 hours to 24 hours.

[0025] In another aspect, the present invention provides an oral preparation comprising the nano-abiraterone acetate composition according to the aforementioned aspects, an absorption promoter, and other excipients.

[0026] Furthermore, in the oral preparation, the absorption promoter includes one or more of ursodeoxycholic acid, sodium chenodeoxycholate and tauroursodeoxycholic acid; the excipients include one of a filler, a solubilizer, a disintegrant, a glidant and a lubricant; the filler includes one or more of sucrose, lactose, microcrystalline cellulose, dextrin, calcium hydrogen phosphate, calcium sulfate, starch, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate and mannitol; the solubilizer includes one or more of polyethoxylated hydrogenated castor oil, poloxamer, sodium dodecylbenzenesulfonate, sodium lauryl sulfate and lecithin; the disintegrant includes sodium carboxymethyl starch, One or more of cross-linked sodium carboxymethyl cellulose, low-substituted cellulose, cross-linked polyvinylpyrrolidone, sodium carboxymethyl starch, calcium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, starch, pregelatinized starch and alginic acid; the glidant includes colloidal silicon dioxide; the lubricant includes one or more of magnesium stearate, stearic acid, palmitic acid, calcium stearate, talc, colloidal silicon dioxide, carnauba wax and sodium stearyl fumarate.

[0027] Furthermore, in the oral preparation, the content of abiraterone acetate is 25-300 mg / unit of oral preparation.

[0028] Furthermore, in the oral preparation, the content of the absorption promoter is 1-15% based on the total weight of the oral preparation.

[0029] Furthermore, the oral preparation is in the form of tablets or capsules.

[0030] Furthermore, in the oral preparation, based on the total weight of the oral preparation, the content of the filler is 35-75%, preferably 40-78%.

[0031] Furthermore, in the oral preparation, the content of the solubilizer is 1.5-5.5%, preferably 2-5%, based on the total weight of the oral preparation.

[0032] Furthermore, in the oral preparation, the content of the disintegrant is 2-12%, preferably 5-9%, based on the total weight of the oral preparation.

[0033] Furthermore, in the oral preparation, the content of the glidant is 0.3-2%, preferably 0.5-1.5%, based on the total weight of the oral preparation.

[0034] Furthermore, in the oral preparation, the content of the lubricant is 0.3-2%, preferably 0.5-1.5%, based on the total weight of the oral preparation.

[0035] Furthermore, the oral preparation is prepared by the following steps: mixing the nano-abiraterone acetate composition, the absorption promoter and other excipients according to a weight ratio, and tableting to obtain an oral preparation containing the nano-abiraterone acetate composition.

[0036] According to the technical solution of the present invention, the following beneficial effects are achieved:

[0037] (1) The nanometer abiraterone acetate composition provided by the present invention has a particle size D90 of abiraterone acetate that can be controlled to be below 450 nm, significantly improving the bioavailability of abiraterone acetate. In addition, the composition further comprises an auxiliary material suspending agent, a surfactant, and a stabilizer. The components in the formula are reasonably matched, which can ensure the dissolution and stability of abiraterone acetate and improve the bioavailability of abiraterone acetate.

[0038] (2) The preparation method of the nano-abiraterone acetate composition provided by the present invention has a simple process and a high success rate, and can solve the agglomeration problem of the abiraterone acetate nanosuspension during the preparation process.

[0039] (3) The oral preparation provided by the present invention comprises raw materials including a nano-abiraterone acetate composition and an absorption enhancer. By utilizing the special properties of the nanocrystalline API and adding bile acid salt absorption enhancers (ursodeoxycholic acid, sodium chenodeoxycholate, tauroursodeoxycholic acid), especially ursodeoxycholic acid, the oral bioavailability can be improved, the dosage of the drug can be reduced, liver damage can be reduced, and the effect of food on drug absorption can be reduced. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] The accompanying drawings are for illustrating exemplary effects of the present invention, in which:

[0041] FIG1 shows the dissolution curves of the homemade abiraterone acetate tablets and the reference tablets provided according to an embodiment of the present invention. DETAILED DESCRIPTION

[0042] The present invention will be further described below in conjunction with the accompanying drawings and specific implementation methods. It should be noted that, under the premise of no conflict, the various embodiments or technical features described below can be arbitrarily combined to form new embodiments.

[0043] Example 1

[0044] A nano-abiraterone acetate composition, the formula of which is shown in Table 1 below:

[0045] Table 1 Nano-abiraterone acetate composition formula

[0046] Weigh 42.0g of copovidone VA64, 5.0g of SDS, and 5.0g of BHA into 5000g of pure water and stir until the solution is clear to obtain an excipient solution. Weigh 120.0g of the abiraterone acetate API and slowly add it to the stirring excipient solution to disperse it into the excipient solution to obtain a pre-grinding suspension. Add grinding beads to the grinding chamber and add the suspension to the grinder feed funnel. Set the speed to 2000rpm / s and grind for 3h to obtain the abiraterone acetate nanosuspension.

[0047] The prepared abiraterone acetate nanosuspension was spread evenly on a stainless steel plate, placed in a freeze dryer and freeze-dried at -50°C for 30 hours to obtain abiraterone acetate freeze-dried powder.

[0048] The excipients (275.0 g of microcrystalline cellulose PH101, 25.0 g of croscarmellose sodium, 15.0 g of ursodeoxycholic acid, 5.0 g of colloidal silicon dioxide, and 6.0 g of magnesium stearate) were accurately weighed according to the prescription. The prepared abiraterone acetate lyophilized powder and the weighed excipients were passed through a 40-mesh sieve and then placed in a three-dimensional mixer and mixed uniformly. The mixed powder was then placed in the tablet press hopper for tableting to produce oral tablets.

[0049] Example 2

[0050] A nano-abiraterone acetate composition, the formula of which is shown in Table 2 below:

[0051] Table 2 Nano-abiraterone acetate composition formula

[0052] Weigh 68.0g of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, 5.0g of SDS and 5.0g of BHA, add to 5000g of pure water, stir until the solution is clear, and obtain an auxiliary material solution. Weigh 127.0g of abiraterone acetate bulk drug, slowly add the auxiliary material solution in the above stirring, and disperse it in the auxiliary material solution to obtain a pre-grinding suspension. Add grinding beads to the grinding chamber, add the suspension to the grinder feed funnel, set the speed to 2000rpm / s, and grind for 3h to obtain an abiraterone acetate nanosuspension.

[0053] The prepared abiraterone acetate nanosuspension was spread evenly on a stainless steel plate, placed in a freeze dryer and freeze-dried at -50°C for 30 hours to obtain abiraterone acetate freeze-dried powder.

[0054] The excipients (230.0 g lactose, 40.0 g croscarmellose sodium, 15.0 g ursodeoxycholic acid, 5.0 g colloidal silicon dioxide, and 6.0 g magnesium stearate) were accurately weighed according to the prescription. The prepared abiraterone acetate lyophilized powder and the weighed excipients were passed through a 40-mesh sieve and then placed in a three-dimensional mixer and mixed uniformly. The mixed powder was then placed in the tablet press hopper for tableting to produce oral tablets.

[0055] Comparative Example 1

[0056] A nanometer abiraterone acetate composition, the formula of which is shown in Table 3 below:

[0057] Table 3 Nano-abiraterone acetate composition formula

[0058] Weigh 47.0 g of copovidone VA64, 5.0 g of SDS, and 5.0 g of BHA into 5000 g of pure water and stir until the solution is clear to obtain an excipient solution. Weigh 130.0 g of abiraterone acetate API and slowly add it to the stirring excipient solution. Then stir to obtain an abiraterone acetate nanosuspension.

[0059] The prepared abiraterone acetate nanosuspension was spread evenly on a stainless steel plate, placed in a freeze dryer and freeze-dried at -50°C for 30 hours to obtain abiraterone acetate freeze-dried powder.

[0060] The excipients (lactose 170.0 g, croscarmellose sodium 100.0 g, ursodeoxycholic acid 25.0 g, colloidal silicon dioxide 18.0 g, magnesium stearate 3.0 g) were accurately weighed according to the prescription. The prepared abiraterone acetate lyophilized powder and the weighed excipients were passed through a 40-mesh sieve and then placed in a three-dimensional mixer and mixed uniformly. The mixed powder was then placed in the tablet press hopper for tableting to produce oral tablets.

[0061] Comparative Example 2

[0062] A nano-abiraterone acetate composition, the formula of which is shown in Table 4 below:

[0063] Table 4 Nano-abiraterone acetate composition formula

[0064] Weigh 48.0g of copovidone VA64, 5.0g of SDS, and 5.0g of BHA into 5000g of pure water and stir until the solution is clear to obtain an excipient solution. Weigh 130.0g of the abiraterone acetate API and slowly add it to the stirring excipient solution to disperse it into the excipient solution to obtain a pre-grinding suspension. Add grinding beads to the grinding chamber and add the suspension to the grinder feed funnel. Set the speed to 2000rpm / s and grind for 3h to obtain an abiraterone acetate nanosuspension.

[0065] The prepared abiraterone acetate nanosuspension was spread evenly on a stainless steel plate, placed in a freeze dryer and freeze-dried at -50°C for 30 hours to obtain abiraterone acetate freeze-dried powder.

[0066] According to the prescription, the excipients (lactose 180.0g, microcrystalline cellulose PH101 95.0g, cross-linked carboxymethyl cellulose sodium 20.0g, colloidal silicon dioxide 6.0g, magnesium stearate 3.0g) were accurately weighed. The prepared abiraterone acetate lyophilized powder and the weighed excipients were passed through a 40-mesh sieve and then loaded into a three-dimensional mixer and mixed evenly. The mixed powder was then loaded into the tablet press hopper for tableting to obtain oral tablets.

[0067] Effect verification

[0068] In vitro dissolution test

[0069] According to the second method (paddle method) of the dissolution determination of the Chinese Pharmacopoeia 2020 edition, the dissolution test of the reference preparation (original drug Zytiga, 250 mg) was compared, and 900 ml of water containing 2.0% SDS solution was used as the dissolution medium. The specific dissolution data are shown in Table 5 below.

[0070] Table 5 Dissolution (%) (Dissolution medium: water + 2.0% SDS)

[0071] Figure 1 shows the dissolution curves for the tablets of Examples 1-2, Comparative Examples 1-2, and a reference tablet. It can be seen that the dissolution rates of the tablets of Examples 1-2 are superior to those of the reference preparation and the unground tablets of Comparative Example 1. Furthermore, compared to the tablets of Comparative Example 2, the addition of the absorption enhancer ursodeoxycholic acid in the tablets of Example 1-2 significantly improved their dissolution rates.

[0072] Pharmacokinetic testing

[0073] A pharmacokinetic study was conducted in three male dogs over a six-cycle trial. The dogs were orally administered with one tablet of Example 1 (recorded as T1, strength: 125 mg), one tablet of Example 2 (recorded as T2, strength: 125 mg), and one tablet of the original drug Zytiga (recorded as R, strength: 250 mg) on ​​an empty stomach. The dogs were then orally administered with one tablet of Example 1 (recorded as T1, strength: 125 mg) and one tablet of the original drug Zytiga (recorded as R, strength: 250 mg) after a meal. The dogs were then orally administered with one tablet of Comparative Example 2 (recorded as T4, strength: 125 mg) on ​​an empty stomach. Blood samples were collected, and plasma abiraterone concentrations were determined. Key pharmacokinetic parameters were calculated. See Table 6 for details.

[0074] Table 6 Pharmacokinetic experiments

[0075] Note: R: Abiraterone acetate tablets, 1 tablet / dog, i.e. 250 mg / dog.

[0076] Test subjects: 3 healthy Male beagle dogs were enrolled in the study, designated group G1, and the five cycles were designated P1, P2, P3, P4, P5, and P6. All animals underwent a 7-day washout period between cycles. Water was freely available during the study. Animals in the oral administration group fasted overnight (10-14 hours) prior to administration and were fed 4 hours after administration. Animals in the postprandial oral administration group were administered without fasting. All preparations were administered with 50 ml of water, and the animals were fed 4 hours after administration.

[0077] Blood was collected at the following times: 0, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, and 24 hours. Blood was collected from the forelimb vein or other suitable vein. The blood volume per collection was approximately 0.5 mL. The sample blood was transported and centrifuged under the same conditions as the blank blood. Within half an hour of collection, the upper plasma layer (0.2 mL per sample (0.1 mL x 2, with a backup aliquot)) was separated into labeled EP tubes and stored at -60°C or below.

[0078] Result analysis: The pharmacokinetic parameters were calculated using Phoenix WinNonlin7.0 based on the blood drug concentration data at different time points, and the AUC 0-t , AUC 0-∞ 、C max 、T max and T 1 / 2 The parameters and their mean and standard deviations are shown in Table 7.

[0079] Table 7 Pharmacokinetic parameters of original drug Zytiga 250mg vs. nano-abitucate acetate tablets 125mg

[0080] Note: T max is the peak time, C max is the maximum plasma concentration (peak concentration), AUC 0-t It is the AUC (area under the curve) from the start of drug administration to the last point.

[0081] Conclusion: As shown in Table 7, the AUC of beagle dogs after oral administration of one tablet of Example 1 (T1, specification 125 mg) and one tablet of Example 2 (T2, specification 125 mg) on ​​an empty stomach was significantly improved compared with the original drug Zytiga (R, specification 250 mg). 0-t The bioavailability of Example 1 tablet (T1) and Example 2 tablet (T2) was 4.9 times and 3.74 times that of the original drug reference agent Zytiga (R, specification 250 mg) respectively. The effect of food on AUC was compared between oral administration of one tablet of Example 1 (T1, specification 125 mg) after a meal and oral administration of one tablet of Example 1 (T1, specification 125 mg) on ​​an empty stomach in beagle dogs. 0-t In contrast, when beagle dogs were given one tablet of the reference drug Zytiga (R, specification 250 mg) orally after a meal, compared with one tablet of the reference drug Zytiga (R, specification 250 mg) orally on an empty stomach, food had no effect on AUC 0-t The effect of the fasting oral administration of one tablet of Example 1 (T1, specification 125 mg) to beagle dogs was 23.94 times greater than that of the fasting oral administration of one tablet of Comparative Example 2 (T4, specification 125 mg) without the addition of an absorption enhancer. 0-t and C max Reaching 2.04 times and 1.93 times respectively. This shows that the nano-abiraterone acetate tablets developed by the present invention increase the intestinal absorption of nano-abiraterone acetate by the addition of a stimulant compared with the original drug Zytiga (specification 250 mg) and the tablets of Comparative Example 2, thereby greatly improving the bioavailability of nanocrystalline abiraterone acetate. It is possible to achieve an equivalent therapeutic effect by reducing the dosage of the drug and reduce the loss of the drug to the liver. At the same time, the nanocrystalline abiraterone acetate developed by the present invention significantly reduces the effect of food on drug absorption, thereby facilitating the implementation of clinical treatment and the control of safety risks.

[0082] The above embodiments are only preferred embodiments of the present invention and cannot be used to limit the scope of protection of the present invention. Any non-substantial changes and replacements made by technicians in this field on the basis of the present invention fall within the scope of protection required by the present invention.

Claims

1. A nano-acetate abiraterone composition, characterized in that, It contains abiraterone acetate, a suspending agent, a surfactant and a stabilizer in a weight ratio of 1:(0.1 - 4):(6 - 20):(0.01 - 0.1).

2. The nano-acetate abiraterone composition according to claim 1, characterized in that, It contains abiraterone acetate, a suspending agent, a surfactant and a stabilizer in a weight ratio of 1:(0.2 - 0.6):(10 - 15):(0.02 - 0.05).

3. The nano-acetate abiraterone composition according to claim 1, characterized in that, The D90 of abiraterone acetate in the composition is ≤ 450 nm.

4. The nano-acetate abiraterone composition according to claim 1, characterized in that, The suspending agent includes one or any combination of monocaprylate / dicaprylate glycerol, polyethylene glycol glycerol ester, hydroxypropyl cellulose, poloxamer, vinylpyrrolidone / vinyl acetate copolymer, polyethylene glycol, poly(2-ethyl-2-oxazoline), polyvinylpyrrolidone, block copolymer based on ethylene oxide and propylene oxide, poly(maleic acid / methyl vinyl ether) copolymer, polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, polyethylene glycol 15 hydroxystearate, ethylene oxide / propylene oxide block copolymer, polyvinyl alcohol-polyethylene glycol graft copolymer, d-α-tocopheryl polyethylene glycol 1000 succinate, and copovidone VA64.

5. The nano-acetate abiraterone composition according to claim 1, characterized in that, The surfactant includes one or any combination of polyoxyethylene ether, poloxamer, sodium dodecylbenzenesulfonate, sodium dodecyl sulfate, lecithin, Tween 80, Span 80, sodium dioctyl sulfosuccinate, and polyethoxylated hydrogenated castor oil.

6. The nano-acetate abiraterone composition according to claim 1, wherein The stabilizer includes one or any combination of sodium sulfite, sodium metabisulfite, sodium bisulfite, sodium thiosulfate, dibutylphenol, vitamin C, gallate, α-tocopherol, butylated hydroxyanisole, ascorbyl palmitate, tert-butylhydroxyanisole, 2,6-di-tert-butyl-4-methylphenol, and tert-butylhydroquinone.

7. The preparation method of the nano-acetate abiraterone composition according to any one of claims 1-6, characterized in that, It includes the following steps: Prepare a suspension by wet grinding of abiraterone acetate, a suspending agent, a surfactant and a stabilizer according to the weight percentage, and dry and remove water from the suspension to obtain a nano abiraterone acetate composition.

8. The preparation method according to claim 7, wherein Perform vacuum freeze-drying on the suspension to obtain a nano abiraterone acetate composition.

9. An oral preparation, characterized in that, It contains the nano abiraterone acetate composition according to any one of claims 1 - 6, an absorption enhancer and other excipients.

10. The oral preparation according to claim 9, characterized in that, The absorption enhancer is one or more of ursodeoxycholic acid, sodium chenodeoxycholate, and tauroursodeoxycholic acid, and the excipients include one of filler, solubilizer, disintegrant, glidant, and lubricant; the filler includes one or more of sucrose, lactose, microcrystalline cellulose, dextrin, calcium hydrogen phosphate, calcium sulfate, starch, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, and mannitol; the solubilizer includes one or more of polyethoxylated hydrogenated castor oil, poloxamer, sodium dodecylbenzenesulfonate, sodium dodecyl sulfate, and lecithin; the disintegrant includes one or more of sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose, low-substituted cellulose, cross-linked povidone, sodium carboxymethyl starch, calcium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, starch, pregelatinized starch, and alginic acid; the glidant includes colloidal silicon dioxide; the lubricant includes one or more of magnesium stearate, stearic acid, palmitic acid, calcium stearate, talc, colloidal silicon dioxide, carnauba wax, and sodium stearyl fumarate.

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