CN114306236B

CN114306236B - Self-microemulsion system for loading abiraterone acetate, composition and application

Info

Publication number: CN114306236B
Application number: CN202210049441.5A
Authority: CN
Inventors: 易木林
Original assignee: Hunan Huize Bio Pharmaceutical Co ltd
Current assignee: Hunan Huize Bio Pharmaceutical Co ltd
Priority date: 2021-12-15
Filing date: 2022-01-17
Publication date: 2022-10-21
Anticipated expiration: 2042-01-17
Also published as: CA3183820C; CN114306236A; CA3183820A1

Abstract

The invention discloses a self-microemulsion system for loading abiraterone acetate, a composition and application thereof. The self-microemulsion system for loading the abiraterone acetate has excellent solubility and stability for the abiraterone acetate, and the composition formed by dissolving the abiraterone acetate by the system can obviously reduce the influence of food on the absorption of the abiraterone acetate and reduce the difference before meals, so that the medicine can be taken under the conditions of fasting and satiety, and the limitation of the medicine taking time is reduced.

Description

Self-microemulsion system for loading abiraterone acetate, composition and application

Technical Field

The invention relates to the technical field of abiraterone acetate preparations, in particular to a self-microemulsion system for loading abiraterone acetate, a composition and application thereof

Background

Abiraterone acetate is a white to off-white crystalline powder which is not hygroscopic; is chemically named as (3 beta) -17- (3-pyridyl) androst-5, 16-dien-3-yl acetate and has the molecular formula of C ₂₆ H ₃₃ NO ₂ . Abiraterone acetate is converted in vivo to the androgen biosynthesis inhibitor abiraterone, which inhibits 17 α -hydroxylase/C17, 20-lyase (CYP 17). Can be used in combination with prednisone for treating patients who have received previous treatment for metastatic castration-resistant prostate cancer (CRPC) with docetaxel. But instead of the other end of the tubeAbiraterone acetate is a lipophilic compound with an octanol-water partition coefficient of 5.12 (LogP), an aromatic nitrogen pKa of 5.19, almost water-insoluble (less than 0.01 mg/ml), and poor permeability, is a BCS IV drug, and has very low bioavailability upon oral absorption.

The abiraterone acetate original grinding medicine Zytiga is a tablet. Each tablet of Zytiga contains 250mg of abiraterone acetate, and inactive ingredients comprise: colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, and sodium lauryl sulfate. Zytiga has very low oral bioavailability (less than 10%), up to 1000mg per dose, but only less than 10% of the drug is able to exert its effect.

Furthermore, food has a great influence on the absorption of abiraterone acetate and the commercial preparations are required to be taken only a specific time period before meals. The Zytiga specification emphasizes that systemic exposure to abiraterone acetate increases when administered with food. Abiraterone acetate C when given with a low fat diet (7% fat, 300 calories) _max And AUC _0-∞ An increase of about 7-fold and 5-fold, respectively; when abiraterone acetate was given with a high fat (57% fat, 825 calories) diet, C _max And AUC _0-∞ An increase of about 17-fold and 10-fold, respectively. Given the normal variation in the content and composition of meals with which administration may result in increased and highly variable exposures, in order to control abiraterone plasma concentrations, administration must be on an empty stomach and should not take food for at least two hours before and at least 1 hour after administration of the dose. Although abiraterone acetate has good effect in treating advanced prostate cancer through oral administration, the characteristics of low solubility and poor permeability bring obstacles to the design of a preparation.

Yonsa manufactured by SoluMatrix particle technology is adopted by Sun Pharmaceutical Industries Ltd in India, provides an improved abiraterone acetate tablet which can promote the dissolution of abiraterone acetate and improve the oral bioavailability by 1 time compared with the original ground medicament Zytiga. Although the dose of Yonsa is reduced to 500mg, the crystal form and the size of the drug are only changed, the dissolution rate of the drug is improved, and the permeability of the abiraterone acetate to gastrointestinal epithelial cells is not increased, so that the oral bioavailability of Yonsa is still low.

Patent document CN107278152A relates to an abiraterone acetate complex, a preparation method thereof and a pharmaceutical composition containing the same, which comprises 5-40 wt% of abiraterone acetate, 5-80 wt% of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and 0.1-50 wt% of sodium deoxycholate. The compound can reduce food effect and give up the requirement of taking medicine on an empty stomach, and can improve the oral bioavailability by 5 times at most, but the preparation process of the compound preparation is complex. Patent document WO2021057042 discloses a self-microemulsion composition of abiraterone acetate, and a preparation method and application thereof, wherein the composition comprises, by mass, 5-20% of abiraterone acetate, 20-50% of an oil phase, 20-60% of an emulsifier, and 20-80% of an auxiliary emulsifier. The pharmaceutical composition can be completely dissolved by strong mechanical stirring in the dissolving process, and the bioavailability is still to be improved after oral administration.

Disclosure of Invention

Aiming at the defects of the prior art, the invention aims to provide a self-microemulsion system for loading abiraterone acetate, and a method for preparing an abiraterone acetate composition by using the system and application of the system. The self-microemulsion system for loading the abiraterone acetate has excellent solubility and stability for the abiraterone acetate, and the composition formed by dissolving the abiraterone acetate by the system can obviously reduce the influence of food on the absorption of the abiraterone acetate and reduce the difference before meals, so that the medicine can be taken under the conditions of fasting and satiety, and the limitation of the medicine taking time is reduced.

In order to achieve the purpose, the technical scheme adopted by the invention is as follows:

according to a first embodiment of the invention, a self-microemulsion system for supporting abiraterone acetate is provided.

A self-microemulsion system for loading abiraterone acetate comprises an oil phase and an emulsion phase, wherein the mass percentage of the oil phase to the emulsion phase is 30% -38% to 62% -70%, preferably 31% -35% to 65% -69%, more preferably 32% -34% to 66% -68%. For example, the mass ratio of 30% to 70%, 31% to 69%, 32% to 68%, 32.5% to 67.5%, 33% to 67%, 33.5% to 66.5%, 34% to 66%, 34.5% to 65.5%, 35% to 65%.

Preferably, the oily phase comprises glycerol monolinoleate (CC) and Medium Chain Triglycerides (MCT).

Preferably, the emulsion phase comprises polyoxyethylene 40 hydrogenated castor oil (RH 40) and diethylene glycol monoethyl ether (HP).

Preferably, in the oil phase, the mass ratio of the glycerol monolinoleate to the medium chain triglyceride is 2.5 to 3.63.

Preferably, in the emulsion phase, the mass ratio of the polyoxyethylene 40 hydrogenated castor oil to the diethylene glycol monoethyl ether is 1.

Preferably, in the oil phase, the mass ratio of the glycerol monolinoleate to the medium chain triglyceride is 2.8-3.5.

Preferably, in the oil phase, the mass ratio of the glycerol monolinoleate to the medium chain triglyceride is 3.0 to 3.4.

In the present invention, in the self-microemulsion system composed of the oil phase and the emulsion phase, the larger the proportion of the emulsion phase (wt%, based on the total mass of the self-microemulsion system composed of the oil phase and the emulsion phase) is, the larger the ratio of diethylene glycol monoethyl ether (HP)/polyoxyethylene 40 hydrogenated castor oil (RH 40) is. Preferably, the ratio of diethylene glycol monoethyl ether (HP)/polyoxyethylene 40 hydrogenated castor oil (RH 40) increases or decreases by 0.05 each time the proportion of the emulsion phase increases or decreases by 1%. Namely: when the ratio of the emulsion phase increases stepwise (1 wt% per step) from 65wt% → 70wt%, the ratio of diethylene glycol monoethyl ether (HP)/polyoxyethylene 40 hydrogenated castor oil (RH 40) increases stepwise (0.05 per step) from 2.25 → 2.5. Conversely, when the ratio of the emulsion phase decreases stepwise from 70wt% → 65wt% (1 wt% per step), the ratio of diethylene glycol monoethyl ether (HP)/polyoxyethylene 40 hydrogenated castor oil (RH 40) also decreases stepwise from 2.5 → 2.25 (0.05 per step).

In the invention, the monolinolein, the medium-chain triglyceride, the polyoxyethylene 40 hydrogenated castor oil, the diethylene glycol monoethyl ether and the like are mixed according to a proportion, and the self-microemulsion system can be obtained after uniform mixing. For example: firstly, mixing the linoleic acid monoglyceride and the medium chain triglyceride according to a proportion to obtain an oil phase; then mixing polyoxyethylene 40 hydrogenated castor oil and diethylene glycol monoethyl ether according to a proportion to obtain an emulsion phase; and finally, uniformly mixing the oil phase and the emulsion phase.

According to a second embodiment of the present invention, there is provided a composition comprising abiraterone acetate.

A composition comprising abiraterone acetate, the composition comprising abiraterone acetate and a self-microemulsion system as described in the first embodiment. Wherein the mass percentage of the abiraterone acetate to the self-microemulsion system is 4.3-4.8% to 95.2-95.7%, preferably 4.4-4.6% to 95.4-95.6%. For example, the mass ratio of 4.3% to 95.7%, 4.4% to 95.6%, 4.5% to 95.5%, 4.6% to 95.4%, 4.7% to 95.3%, 4.8% to 95.2%.

Preferably, the composition of each component of the composition is specifically as follows:

abiraterone acetate: 4.3 to 4.8 wt.%, preferably 4.4 to 4.6 wt.%. For example, 4.3wt%, 4.4wt%, 4.5wt%, 4.6wt%, 4.7wt%, 4.8wt%,

glycerol monolinoleate: 21.4 to 26.2 percent, preferably 22.0 to 26.0 percent. For example, 21wt%, 21.2wt%, 21.4wt%, 21.6wt%, 21.8wt%, 22wt%, 22.2wt%, 22.5wt%, 22.8wt%, 23wt%, 23.3wt%, 23.5wt%, 23.8wt%, 24wt%, 24.3wt%, 24.5wt%, 24.8wt%, 25wt%, 25.2wt%, 25.4wt%, 25.6wt%, 25.8wt%, 26wt%, 26.2 wt%.

Medium chain triglycerides: 6.2 to 9.6 percent, preferably 6.8 to 8.8 percent. For example, 6.2wt%, 6.3wt%, 6.4wt%, 6.5wt%, 6.6wt%, 6.7wt%, 6.8wt%, 6.9wt%, 7.0wt%, 7.1wt%, 7.2wt%, 7.3wt%, 7.4wt%, 7.5wt%, 7.6wt%, 7.7wt%, 7.8wt%, 7.9wt%, 8.0wt%, 8.2wt%, 8.3wt%, 8.4wt%, 8.5wt%, 8.6wt%, 8.7wt%, 8.8wt%, 8.9wt%, 9.0wt%, 9.1wt%, 9.2wt%, 9.3wt%, 9.4wt%, 9.5wt%, 9.6 wt%.

Polyoxyethylene 40 hydrogenated castor oil: 17.7-19.7%, preferably 18.5-19.5%. For example, 17.7wt%, 17.8wt%, 17.9wt%, 18.0wt%, 18.1wt%, 18.2wt%, 18.3wt%, 18.4wt%, 18.5wt%, 18.6wt%, 18.7wt%, 18.8wt%, 18.9wt%, 19.0wt%, 19.1wt%, 19.2wt%, 19.3wt%, 19.4wt%, 19.5wt%, 19.6wt%, 19.7 wt%.

Diethylene glycol monoethyl ether: 42.8-47.8%, preferably 43.0-47.2%. For example, 42.8wt%, 43wt%, 43.2wt%, 43.3wt%, 43.4wt%, 43.5wt%, 43.6wt%, 43.7wt%, 43.8wt%, 44wt%, 44.3wt%, 44.5wt%, 44.8wt%, 45wt%, 45.3wt%, 45.5wt%, 45.8wt%, 46.1wt%, 46.5wt%, 46.8wt%, 47.1wt%, 47.5wt%, 47.8wt%.

Preferably, the composition further comprises optional antioxidant and/or preservative, wherein the antioxidant and/or preservative accounts for 0.005-0.1% of the total mass of the composition. Optional means with or without.

In the invention, abiraterone acetate is dissolved in a self-microemulsion system according to a proportion, then an antioxidant and/or a preservative are optionally added or not added, and the composition containing the abiraterone acetate is obtained after uniform mixing. For example: proportionally and uniformly mixing the glycerol monolinoleate, the medium-chain triglyceride and the polyoxyethylene 40 hydrogenated castor oil (at room temperature or under heating), then adding the abiraterone acetate, stirring in a dark place, uniformly mixing, and finally adding the diethylene glycol monoethyl ether and the optional antioxidant and/or the preservative, and uniformly mixing.

According to a third embodiment of the present invention, there is provided an abiraterone acetate formulation.

An abiraterone acetate preparation comprises a solid preparation and a liquid preparation. Wherein, the solid preparation comprises but not limited to one or more of tablets, capsules, granules, powder, dripping pills and films. The liquid preparation includes but is not limited to one or more of injection, soft capsule, ointment, suppository and aerosol.

Preferably, the solid preparation is prepared from the contents and the auxiliary materials through one or more steps of crushing, sieving, mixing, granulating and tabletting. The auxiliary materials are selected from one or more of fillers, adsorbents, binders, lubricants, dispersants, disintegrants, wetting agents, spices and pigments. The content is the self-microemulsion system and the abiraterone acetate of the first embodiment, or the content is the composition containing the abiraterone acetate of the second embodiment.

The liquid preparation consists of contents and auxiliary agents. The auxiliary agent is selected from one or more of preservative, stabilizer, antioxidant, aromatic, osmotic pressure regulator and flavoring agent. The content is the self-microemulsion system and the abiraterone acetate of the first embodiment, or the content is the composition containing the abiraterone acetate of the second embodiment.

In the invention, the preparation method of the abiraterone acetate preparation can be prepared by a person skilled in the art according to the preparation method of the conventional preparation in the art to obtain the corresponding preparation. For example: preparing a composition containing abiraterone acetate according to the method; sealing the composition containing abiraterone acetate in a soft capsule or a hard capsule; preferably, each capsule contains 0.5-1ml of the abiraterone acetate-containing composition.

In the composition containing the abiraterone acetate, the concentration of the abiraterone acetate can be controlled to be 50-100mg/mL, and the single oral dose is 75-100mg. Mixing with water, biologically relevant medium (such as SGF, fessiF and FassiF medium) or gastrointestinal fluid, and spontaneously forming O/W nanoemulsion with high clarity, uniform particle size and stable property, and particle size of less than 250 nm; the contents can exist in the form of a stable solution when stored at room temperature; the self-microemulsifying compositions of the present invention are stable even under conditions of influence (e.g. 30 ℃. + -. 2 ℃, 4 ℃, addition of 10wt% water based on the composition, addition of 15wt% water based on the composition).

According to a fourth embodiment of the present invention, there is provided a pharmaceutical composition.

A pharmaceutical composition comprising one of the abiraterone acetate-containing composition of the second embodiment and the abiraterone acetate formulation of the third embodiment, and prednisone. Namely the combination of the abiraterone acetate-containing composition and prednisone or the combination of the abiraterone acetate preparation and prednisone.

According to a fifth embodiment of the present invention, there is provided the use of the abiraterone acetate-containing composition of the second embodiment or the abiraterone acetate formulation of the third embodiment or the pharmaceutical composition of the fourth embodiment: the abiraterone acetate-containing composition of the second embodiment or the abiraterone acetate formulation of the third embodiment or the pharmaceutical composition of the fourth embodiment is used for preparing a pharmaceutical formulation for treating prostate cancer.

Preferably, the prostate cancer is selected from one or both of metastatic castration-resistant prostate cancer and metastatic high-risk castration-sensitive prostate cancer. Generally, the administration of the drug of the present invention can be either before or after a meal.

In the prior art, abiraterone acetate as a BSC IV drug has low solubility and low permeability, and in the process of developing a dosage form, the solubility of the abiraterone needs to be solved, and more importantly, the transmembrane problem of the abiraterone in the absorption process needs to be solved. The existing preparation can effectively solve the problems of solubility and dissolution of abiraterone acetate, but the problem of absorption and transmembrane of the medicine in vivo is not effectively solved, and the bioavailability is not effectively improved. And the existing preparation formulation also cannot effectively solve the problem of moisture absorption and precipitation of abiraterone acetate, so that the stability of the abiraterone acetate is low. Meanwhile, the proportion of an oil phase and an emulsion phase is not reasonably controlled in the self-microemulsion system for loading abiraterone acetate in the prior art, so that diethylene glycol monoethyl ether in the emulsion phase is too much (toxic and side effects can be caused) or too low (microemulsion is difficult or can not be formed).

In the invention, the composition containing abiraterone acetate is a solution system, and can spontaneously disperse under gastrointestinal motility to form O/W type nanoemulsion after oral administration when meeting gastrointestinal fluids, and the composition has high clarity, uniform particle size and stable property. The nanoemulsion has small particle size, can promote the dissolution of the medicament, increase the in-vivo membrane permeability of the abiraterone, increase the penetrability of epithelial cells of intestinal tracts, further remarkably promote the absorption and remarkably improve the bioavailability of the medicament. The composition containing the abiraterone acetate can also obviously reduce the influence of food on the absorption of the abiraterone acetate and reduce the difference before meals, so that the medicine can be taken under the conditions of fasting and satiety, and the limitation of the medicine taking time is reduced.

In the invention, the provided self-microemulsion system can be used as a carrier of hydrophobic, difficult-to-absorb or easily-hydrolyzed drugs. The solubility of the abiraterone acetate can be improved at room temperature, and the formed uniform and stable abiraterone acetate-containing drug system can be spontaneously dispersed to form the nanoemulsion after entering the body, so that the problem of absorption and transmembrane of the abiraterone acetate in the body can be effectively solved. Through intensive research, the oral bioavailability of the composition containing abiraterone acetate prepared by the invention is greatly improved, and the stability of the composition in a humid or over-humid environment is excellent. Compared with microemulsion, the self-emulsifying solution has higher stability, can meet the requirement of long-term storage, and can be directly filled into packages such as soft capsules or hard capsules.

Compared with the prior art, the invention has the following beneficial technical effects:

1: the invention selects specific raw materials to prepare an oil phase and an emulsion phase according to a specific proportion, and then the oil phase and the emulsion phase are mixed according to a specific proportion to obtain the self-microemulsion system for loading the abiraterone acetate. The self-microemulsion system has high solubility and strong stability to abiraterone acetate, can form O/W type nano-emulsion by spontaneous dispersion under gastrointestinal motility, and has high clarity, uniform particle size and stable property; greatly improves the membrane permeability of the abiraterone acetate in vivo, increases the penetrability of intestinal epithelial cells, further remarkably promotes absorption and improves the bioavailability of the medicament.

2: the composition containing the abiraterone acetate is prepared by the abiraterone acetate and a self-made self-microemulsion system, so that the influence of food on the absorption of the abiraterone acetate can be obviously reduced, the difference before meals and after meals is obviously reduced, the medicine can be taken under the conditions of fasting and satiety, and the limitation of the medicine taking time is reduced.

Drawings

Fig. 1 is a ternary phase diagram plotted for HP, RH40 and (CC: MCT =1 0) scaled dose studies.

Fig. 2 is a ternary phase diagram plotted for HP, RH40 and (CC: MCT = 1) scaled dose studies.

Fig. 3 is a ternary phase diagram plotted for HP, RH40 and (CC: MCT = 2).

Fig. 4 is a ternary phase diagram plotted for HP, RH40 and (CC: MCT =1 2) scaled dose studies.

Fig. 5 is a ternary phase diagram plotted for HP, RH40 and (CC: MCT = 3) scaled dose considerations.

Fig. 6 is a ternary phase diagram plotted for HP, RH40 and (CC: MCT =1 3) scaled dose studies.

Fig. 7 is a ternary phase diagram plotted for HP, RH40 and (CC: MCT = 5) scaled dose studies.

Fig. 8 is a ternary phase diagram plotted for HP, RH40 and (CC: MCT = 1).

Figure 9 is a photograph of samples of the abiraterone acetate-containing compositions of comparative examples 1-4 after setting out at 4 ℃ for 24 h.

Figure 10 is a photograph of samples of abiraterone acetate-containing compositions of example 2 and comparative examples 1-4 after setting out for 24h at room temperature with the addition of 10wt% water.

FIG. 11 is a photograph of samples of the abiraterone acetate-containing compositions of example 2 and comparative examples 1-4 after setting out for 24h at room temperature with the addition of 15wt% water.

Detailed Description

The technical solutions of the present invention are illustrated below, and the claimed scope of the present invention includes, but is not limited to, the following examples.

Test 1: construction test of self-microemulsion system:

mixing glycerol monolinoleate (CC) with medium-chain triglycerides (MCT) in different mass ratios (

mass ratio

1, 2, 3, 1, 5; polyoxyethylene 40 hydrogenated castor oil (RH 40) and diethylene glycol monoethyl ether (HP) were mixed at different mass ratios (

mass ratio

1, 2, 3. Then, the oil phase and the emulsion phase are mixed at different mass ratios (mass ratio is 9, 2, 7, 3, 6, 4, 5, 6, 3, 7,2, 8, 1).

As can be seen from figures 1-8: the use of a combination of mono-and medium-chain triglycerides as the oil phase is more effective than the use of mono-and medium-chain triglycerides alone as the oil phase (as shown in fig. 1-8, fig. 1 represents a ternary phase diagram when mono-and medium-chain triglycerides are used alone as the oil phase, fig. 2-7 represents a ternary phase diagram when mono-and medium-chain triglycerides are used together at different mass ratios, it can be seen that the micro-emulsification zone area of fig. 1 is the smallest, for example, in comparison with fig. 1 and 2, when mono-and medium-chain triglycerides are used together, the micro-emulsification can still be formed when the oil phase is 50%, but when only mono-and medium-chain triglycerides are used together, no matter how the ratio of RH40 to HP is adjusted, the system can not form a micro-emulsified state), so that the self-micro-emulsion system of the present invention selects a mixed oil phase of mono-and medium-chain triglycerides (MCT) as the oil phase. Meanwhile, the following test results show that: abiraterone acetate has a solubility (25 ℃) of about 62.9mg/g in glycerol monolinoleate (CC) and a solubility (25 ℃) of about 28.4mg/g in Medium Chain Triglycerides (MCT). When using glycerol monolinoleate in combination with medium chain triglycerides as the oil phase, the amount of CC in the oil phase should be as high as possible and MCT as low as possible in order to ensure a high drug load. In the research process, when the dosage and the mixing ratio of the emulsion phase are unchanged, and the dosage ratio of the glycerol monolinoleate to the medium-chain triglyceride is changed from 2 to 5, the area of a micro-emulsification region in a ternary phase diagram is gradually reduced (the smaller the area, the smaller the area of the region where the micro-emulsion exists is, and the smaller the dosage of the auxiliary material can obtain the micro-emulsification only in the small area, so that the dosage of the auxiliary material is relatively limited, on one hand, the loading capacity of the API is easily limited, and on the other hand, the self-emulsification effect of a self-microemulsion system is influenced). Further experiments and calculations also found that: when the ratio of CC to MCT in the oil phase is 2.5-3.63 (preferably 2.8-3.5, more preferably 3.0-3.4).

Through the test, the following results are found: the effect of combining polyoxyethylene 40 hydrogenated castor oil (RH 40) and diethylene glycol monoethyl ether (HP) as an emulsion phase is better than that of singly using polyoxyethylene 40 hydrogenated castor oil (RH 40) as the emulsion phase, because the diethylene glycol monoethyl ether (HP) can play a role in emulsification assistance, and meanwhile, the using amount of the polyoxyethylene 40 hydrogenated castor oil (RH 40) can be reduced, and the loading amount of abiraterone acetate is increased. The test finds that: abiraterone acetate has a solubility (25 ℃) of about 24.7mg/g in polyoxyethylene 40 hydrogenated castor oil (RH 40) and a solubility (25 ℃) of about 69.0mg/g in diethylene glycol monoethyl ether (HP). When polyoxyethylene 40 hydrogenated castor oil (RH 40) is used in combination with diethylene glycol monoethyl ether (HP) as the emulsion phase, the amount of RH40 in the emulsion phase should be as low as possible and the amount of HP should be as high as possible in order to ensure a large drug loading while ensuring the emulsifying effect from the microemulsion system. In the research process, when the dosage and the mixing ratio of the oil phase are unchanged, the dosage ratio of the polyoxyethylene 40 hydrogenated castor oil to the diethylene glycol monoethyl ether is changed from 1 to 1. And further experiments show that: when the ratio of RH40: HP in the emulsion phase is 1.25-2.5, the abiraterone acetate has excellent loading effect, the self-emulsifying effect of the self-microemulsion system formed by the abiraterone acetate and the oil phase is good, and meanwhile, the auxiliary emulsifier (namely HP) is contained and shielded by the self-microemulsion system, so that the side effect is hardly generated.

In a preferred embodiment of the invention: according to the mass ratio: mixing CC and MCT =3.38 to obtain an oil phase, wherein the oil phase comprises the following components in percentage by mass: RH40: HP = 1; mixing the oil phase and the emulsion phase according to different mass ratios to obtain a mixed system, and inspecting the emulsification effect of the mixed system; the mixing ratio of the oil phase and the emulsion phase is shown in table 1:

table 1 emulsification effect test results one

Oil phase/g	Milk phase/g	Water consumption per gram in the form of microemulsion	Emulsified state
				0.9	0.1	-	No emulsification, obvious oil drop
0.8	0.2	-	No emulsification, obvious oil drop
				0.7	0.3	-	Grayish white turbidity with visible oil droplets
0.6	0.4	-	Grayish white turbidity with visible oil droplets
				0.5	0.5	-	Opalescent turbidity
0.4	0.6	748.6	Microemulsion with blue light and high turbidity
				0.3	0.7	18.2	Microemulsion with blue light
0.2	0.8	6.1	Slightly blue light microemulsion
				0.1	0.9	6.3	Colorless transparent microemulsion

Therefore, as can be seen from the test results of table 1: the amount of the emulsion phase needs to be more than or equal to 60wt% (based on the total mass of the oil phase and the emulsion phase), a mixed system consisting of the oil phase and the emulsion phase can form a self-emulsifying effect, and the amount ratio of the oil phase to the emulsion phase is further optimized in order to ensure the self-emulsification and reduce the amount of an emulsifier (namely RH 40). The results are shown in Table 2:

table 2 emulsification effect test results 2

Therefore, as can be seen from the test results of table 2: when the water consumption is 100g, the total amount of the oil phase in a mixed system (i.e. self-microemulsion system) consisting of the oil phase and the emulsion phase is less than or equal to 35wt%, and the total amount of the emulsion phase is greater than or equal to 65wt%. The self-microemulsion system has good emulsification effect. In order to ensure self-emulsification and reduce the amount of the emulsifier (i.e., RH 40), the weight percentage of the oil phase and the emulsion phase in the self-microemulsion system is 32wt% -35wt%, 65wt% -68wt%, preferably 33wt% -35wt%, 65wt% -67wt%, more preferably 35wt% -65 wt%. (based on the total mass of the oil phase and the emulsion phase).

Test 2: the self-microemulsion system drug loading capacity investigation test comprises the following steps:

2.1: mixing at a mass ratio of CC: MCT =3.63 to obtain an oil phase, and mixing at a mass ratio of RH40: HP =1 to obtain an emulsion phase; and mixing the oil phase and the emulsion phase according to the mass ratio of 30wt% to 70wt% to obtain the self-microemulsion system for loading the abiraterone acetate. The self-microemulsion system was used to load abiraterone Acetate (API) with different mass content, and the results are shown in table 3:

table 3: API load test result one

2.2: mixing at a mass ratio of CC: MCT =2.5 to obtain an oil phase, mixing at a mass ratio of RH40: HP =1 to obtain an emulsion phase; and mixing the oil phase with the emulsion phase according to the mass ratio of 35wt% to 65wt% to obtain the self-microemulsion system for loading the abiraterone acetate. The self-microemulsion system was used to load abiraterone Acetate (API) with different mass content, and the results are shown in table 4:

table 4: API load test result two

As can be seen from tables 3 and 4, the maximum effective drug loading amount of the self-microemulsion system provided by the present solution to abiraterone acetate should be 4.5wt% to 4.8wt% (based on the total mass of the API and the self-microemulsion system), and in order to ensure the drug loading amount, the content of abiraterone acetate obtained by research and calculation should be not less than 4.3wt% (the content is too low, so that the dosage of the drug taken by the patient is increased, thereby causing the dosage of the auxiliary material serving as the carrier to be increased, and easily causing toxic and side effects).

Example 1

A composition containing abiraterone acetate comprises the following components:

abiraterone acetate: 1.118 parts by weight (about 4.30% by weight of the total mass of the composition).

Glycerol monolinoleate: 6.722 parts by weight (about 25.85wt% of the total mass of the composition).

Medium chain triglycerides: 1.991 weight parts (about 7.66wt% of the total composition mass).

Polyoxyethylene 40 hydrogenated castor oil: 4.973 parts by weight (about 19.13wt% of the total mass of the composition).

Diethylene glycol monoethyl ether: 11.196 parts by weight (about 43.06wt% of the total mass of the composition).

The preparation process comprises the following steps: taking the glyceryl monolinoleate, the medium-chain triglyceride and the polyoxyethylene 40 hydrogenated castor oil according to the proportion, stirring and mixing uniformly, then adding the abiraterone acetate, keeping out of the sun, adding the diethylene glycol monoethyl ether after fully dissolving, and obtaining the composition containing the abiraterone acetate after forming a transparent and uniform self-emulsifying solution.

Example 2

abiraterone acetate: 1.170 parts by weight (about 4.50wt% of the total mass of the composition).

Glycerol monolinoleate: 6.704 parts by weight (about 25.78wt% of the total mass of the composition).

Medium chain triglycerides: 1.986 parts by weight (in a ratio of about 7.64% by weight of the total mass of the composition).

Polyoxyethylene 40 hydrogenated castor oil: 4.966 parts by weight (about 19.10wt% based on the total mass of the composition).

Diethylene glycol monoethyl ether: 11.174 parts by weight (at a ratio of about 42.98wt% of the total mass of the composition).

The preparation process comprises the following steps: taking the glycerol monolinoleate, the medium-chain triglyceride and the polyoxyethylene 40 hydrogenated castor oil according to the proportion, stirring and mixing uniformly, then adding the abiraterone acetate, keeping out of the sun, adding the diethylene glycol monoethyl ether after fully dissolving, and obtaining the composition containing the abiraterone acetate after forming a transparent and uniform self-emulsifying solution.

Example 3

abiraterone acetate: 1.248 parts by weight (about 4.80wt% of the total mass of the composition).

Glycerol monolinoleate: 6.683 weight portions (the weight ratio is about 25.70 weight percent of the total mass of the composition).

Medium chain triglycerides: 1.979 parts by weight (at a ratio of about 7.61wt% of the total mass of the composition).

Polyoxyethylene 40 hydrogenated castor oil: 4.950 parts by weight (about 19.04wt% based on the total mass of the composition).

Diethylene glycol monoethyl ether: 11.140 parts by weight (about 42.85wt% of the total mass of the composition).

Example 4

Glycerol monolinoleate: 6.523 parts by weight (about 25.09wt% of the total mass of the composition).

Medium chain triglycerides: 2.167 parts by weight (at a ratio of about 8.33wt% of the total mass of the composition).

Polyoxyethylene 40 hydrogenated castor oil: 4.966 parts by weight (about 19.10% by weight of the total mass of the composition).

Example 5

Glycerol monolinoleate: 6.207 parts by weight (about 23.87wt% of the total mass of the composition).

Medium chain triglycerides: 2.483 parts by weight (about 9.55wt% of the total mass of the composition).

Example 6

Glycerol monolinoleate: 6.760 parts by weight (in a ratio of about 26.00wt% based on the total mass of the composition).

Medium chain triglycerides: 1.930 parts by weight (in a ratio of about 7.42wt% of the total mass of the composition).

Example 7

Polyoxyethylene 40 hydrogenated castor oil: 4.747 parts by weight (about 18.26wt% of the total mass of the composition).

Diethylene glycol monoethyl ether: 11.393 parts by weight (at a ratio of about 43.82wt% of the total mass of the composition).

Example 8

Polyoxyethylene 40 hydrogenated castor oil: 4.638 parts by weight (at a ratio of about 17.84wt% of the total mass of the composition).

Diethylene glycol monoethyl ether: 11.502 parts by weight (about 44.24wt% of the total mass of the composition).

Example 9

Glycerol monolinoleate: 6.322 parts by weight (at a ratio of about 24.32wt% of the total mass of the composition).

Medium chain triglycerides: 1.872 parts by weight (about 7.20wt% of the total mass of the composition).

Diethylene glycol monoethyl ether: 11.670 parts by weight (about 44.88wt% of the total mass of the composition).

Example 10

Glycerol monolinoleate: 6.130 parts by weight (about 23.58wt% of the total mass of the composition).

Medium chain triglycerides: 1.816 parts by weight (about 6.98wt% of the total mass of the composition).

Diethylene glycol monoethyl ether: 11.918 parts by weight (about 45.84wt% based on the total mass of the composition).

Example 11

Glycerol monolinoleate: 5.747 parts by weight (in a ratio of about 22.10wt% of the total mass of the composition).

Medium chain triglycerides: 1.702 parts by weight (about 6.55wt% of the total mass of the composition).

Diethylene glycol monoethyl ether: 12.415 parts by weight (about 47.75wt% of the total mass of the composition).

Comparative example 1

abiraterone acetate: 1.170 parts by weight (in a ratio of about 7.11% by weight of the total mass of the composition).

Glycerol monolinoleate: 4.136 parts by weight (at a ratio of about 25.13wt% of the total mass of the composition).

Medium chain triglycerides: 2.632 parts by weight (at a ratio of about 15.99wt% of the total mass of the composition).

Polyoxyethylene 40 hydrogenated castor oil: 3.816 parts by weight (about 23.19wt% of the total mass of the composition).

Diethylene glycol monoethyl ether: 4.704 parts by weight (about 28.58wt% of the total mass of the composition).

Comparative example 2

abiraterone acetate: 1.170 parts by weight (at a ratio of about 8.78wt% of the total mass of the composition).

Glycerol monolinoleate: 4.136 parts by weight (at a ratio of about 31.05wt% of the total mass of the composition).

Medium chain triglycerides: 2.632 parts by weight (about 19.76wt% based on the total mass of the composition).

Polyoxyethylene 40 hydrogenated castor oil: 3.816 parts by weight (about 28.64wt% of the total mass of the composition).

Diethylene glycol monoethyl ether: 1.568 parts by weight (ratio is about 11.77wt% of total mass of the composition).

Comparative example 3

abiraterone acetate: 1.170 parts by weight (about 4.03wt% of the total mass of the composition).

Glycerol monolinoleate: 4.136 parts by weight (at a ratio of about 14.26wt% of the total mass of the composition).

Medium chain triglycerides: 2.632 parts by weight (about 9.08wt% based on the total mass of the composition).

Polyoxyethylene 40 hydrogenated castor oil: 3.816 parts by weight (about 13.16wt% of the total mass of the composition).

Diethylene glycol monoethyl ether: 17.248 parts by weight (at a ratio of about 59.47wt% of the total mass of the composition).

Comparative example 4

abiraterone acetate: 1.170 parts by weight (in a ratio of about 2.45wt% based on the total mass of the composition).

Glycerol monolinoleate: 4.136 parts by weight (about 8.65wt% of the total mass of the composition).

Medium chain triglycerides: 2.632 parts by weight (about 5.50wt% based on the total mass of the composition).

Polyoxyethylene 40 hydrogenated castor oil: 3.816 parts by weight (in a ratio of about 7.98wt% of the total mass of the composition).

Diethylene glycol monoethyl ether: 36.064 parts by weight (about 75.42wt% of the total mass of the composition).

Comparative example 5

abiraterone acetate: 1.300 parts by weight (at a ratio of about 5.0wt% of the total mass of the composition).

Glycerol monolinoleate: 6.667 parts by weight (in a ratio of about 25.64wt% of the total mass of the composition).

Medium chain triglycerides: 1.975 parts by weight (to a ratio of about 7.60wt% of the total mass of the composition).

Polyoxyethylene 40 hydrogenated castor oil: 4.940 parts by weight (about 19.00wt% of the total mass of the composition).

Diethylene glycol monoethyl ether: 11.118 parts by weight (about 42.76wt% of the total mass of the composition).

Comparative example 6

Glycerol monolinoleate: 6.822 parts by weight (about 26.24wt% of the total mass of the composition).

Medium chain triglycerides: 1.868 parts by weight (to about 7.18wt% of the total mass of the composition).

Comparative example 7

Medium chain triglycerides: 1.986 parts by weight (about 7.64% by weight of the total mass of the composition).

Polyoxyethylene 40 hydrogenated castor oil: 4.547 parts by weight (at a ratio of about 17.49wt% of the total mass of the composition).

Diethylene glycol monoethyl ether: 11.593 parts by weight (at a ratio of about 44.59% by weight of the total mass of the composition).

Comparative example 8

Polyoxyethylene 40 hydrogenated castor oil: 5.348 parts by weight (about 20.57wt% of the total mass of the composition).

Diethylene glycol monoethyl ether: 12.033 parts by weight (at a ratio of about 46.28wt% to the total mass of the composition).

Comparative example 9

Glycerol monolinoleate: 7.087 weight portions (the weight ratio is about 27.26 weight percent of the total weight of the composition).

Medium chain triglycerides: 2.100 parts by weight (at a ratio of about 8.08wt% of the total mass of the composition).

Polyoxyethylene 40 hydrogenated castor oil: 4.813 parts by weight (at a ratio of about 18.51% by weight of the total mass of the composition).

Diethylene glycol monoethyl ether: 10.830 parts by weight (about 41.65wt% of the total mass of the composition).

Comparative example 10

Polyoxyethylene 40 hydrogenated castor oil: 5.195 parts by weight (at a ratio of about 19.98wt% of the total mass of the composition).

Diethylene glycol monoethyl ether: 11.689 parts by weight (about 44.96wt% based on the total mass of the composition).

Comparative example 11

Polyoxyethylene 40 hydrogenated castor oil: 5.124 parts by weight (about 19.71wt% of the total mass of the composition).

Diethylene glycol monoethyl ether: 11.016 weight parts (the weight ratio is about 42.37wt% of the total weight of the composition).

Comparative example 12

Glycerol monolinoleate: 5.364 parts by weight (at a ratio of about 20.63wt% of the total mass of the composition).

Medium chain triglycerides: 1.588 parts by weight (about 6.11wt% of the total mass of the composition).

Polyoxyethylene 40 hydrogenated castor oil: 5.501 parts by weight (at a ratio of about 21.16wt% of the total mass of the composition).

Diethylene glycol monoethyl ether: 12.377 parts by weight (to a ratio of about 47.60wt% of the total mass of the composition).

Comparative example 13

Glycerol monolinoleate: 6.134 parts by weight (at a ratio of about 23.59% by weight of the total mass of the composition).

Medium chain triglycerides: 2.556 parts by weight (about 9.83wt% of the total mass of the composition).

The preparation process comprises the following steps: taking the glycerol monolinoleate, the medium-chain triglyceride and the polyoxyethylene 40 hydrogenated castor oil according to the proportion, stirring and mixing uniformly, then adding the abiraterone acetate, keeping out of the sun, adding the diethylene glycol monoethyl ether after fully dissolving, and obtaining the composition containing the abiraterone acetate after forming a transparent and uniform self-emulsifying solution. Effect test example 1

Abiraterone acetate-containing compositions were obtained according to the above-described dose configurations of examples 1 to 11 and comparative examples 1 to 8, and the compositional proportions of the compositions obtained in the respective examples are shown in table 5: simultaneously, stability tests were carried out on each abiraterone acetate containing composition: namely, the abiraterone acetate-containing compositions obtained in examples 1 to 11 and comparative examples 1 to 8 were stood on a sample at room temperature, 4 ℃ at room temperature with the addition of 10wt% of water, at room temperature with the addition of 15wt% of water, for 24 hours, and the stability of the abiraterone acetate-containing compositions was observed, and the results are shown in Table 6.

TABLE 5 composition component ratio containing abiraterone acetate

Note: the value of oil phase/emulsion phase is based on the ratio of the total mass of the oil phase and the emulsion phase.

Table 6 stability study of abiraterone acetate containing compositions

In comparative example 1, the API content was relatively too high, exceeding the maximum drug loading of the vehicle, the vehicle and adjuvant precipitated, and the system became cloudy; in comparative example 2, too low HP content and relatively high API content cause API precipitation, drug particle crystals appear at the bottom of the composition, API precipitation occurs in both comparative example 1 and comparative example 2 after a small amount of water is added, and generally, the prepared drug composition tends to absorb moisture during subsequent long-term storage, resulting in increased moisture content; in comparative example 5, the API content was too high, resulting in a large amount of API precipitation; in comparative example 6, the ratio of CC was too large, resulting in a relatively excessive oil phase, and further resulting in oil droplets under humid or over-humid conditions (i.e., after addition of a small amount of water); in comparative example 7, the proportion of HP is too large, a large amount of HP is hydrophilic after being dispersed in water under the humid or over-humid condition, part of the medicine cannot be completely dissolved and separated out, and the content of HP is relatively too high, so that the toxic and side effects of the medicine are easily increased; comparative examples 8, 10 and 11 all have low relative HP content, so that a good emulsification effect cannot be formed (wherein the relative HP content in comparative example 11 is too low to form a micro-emulsion), and a layering phenomenon occurs under a humid or over-humid condition; in comparative example 9, the content of the emulsion phase was low, and microemulsion could not be formed, while the content of the oil phase was relatively high, resulting in a large amount of oil droplets being precipitated under humid or over-humid conditions; in comparative example 12, the content of the oil phase was low, so that the content of the emulsion phase was relatively high, and further, the content of HP was relatively high, and the HP was hydrophilic after being dispersed in water, and a part of the drug was not completely dissolved and precipitated. In comparative example 13, since the content of CC was relatively too low, the loading of the formed self-microemulsion system to API was low, resulting in precipitation of API; in example 7 and example 8, when the oil phase and the emulsion phase are mixed at a certain ratio, the content of HP in the emulsion phase is slightly higher, and a small amount of HP dispersed in water under humid or over-humid conditions is hydrophilic, so that a trace amount of drug cannot be completely dissolved and precipitated.

Further, the self-microemulsion systems obtained after emulsification in example 2 and comparative examples 1 to 4 were set out and placed at a temperature of 30 ℃ ± 5 ℃ for 24h and 48h, respectively, and the stability of the self-microemulsion systems was observed, and the results are shown in table 7:

as can be seen from table 7 above, the support (API) precipitates in both comparative example 3 and comparative example 4 after the self-microemulsion system is formed, indicating that the long-term stability of the self-microemulsion systems is poor; comparative example 4 has a low oil phase content, and in order to form a transparent solution, the content of the additive co-emulsifier (HP) reaches more than 70%, but the co-emulsifier is hydrophilic after being dispersed in water, part of API can not be completely dissolved and precipitated, and in addition, the content of the co-emulsifier is too high, so that the toxic and side effects of the medicine are easily increased; comparative example 3 the relative amount of oil phase was low and the particles were large after emulsification, affecting subsequent absorption and drug precipitation after storage over time.

Application example 1

The pharmacokinetic tests of the abiraterone acetate-containing composition prepared in the present application and example 1 (hereinafter: comparative example 14) in prior art WO2021057042 were carried out:

test methods and objects: healthy beagle dogs, 6, were randomized into 3 groups of 2 dogs each with 3 days of washout between cycles.

The test design is divided into fasting test and postprandial test.

Open web test: fasting for 10 hours before the test, fasting administration, and feeding 4 hours after administration

And (3) postprandial test: fasting was 10 hours before the trial and feeding was given after a high-fat meal (feeding and dosing was completed within 30 minutes).

The test capsules were the abiraterone acetate-containing capsules provided in examples of the present invention and comparative example 14, and a single capsule contained 50mg of abiraterone acetate.

Sampling design: blood samples of 2mL are collected 15min, 30min, 1h, 1.5h, 2.0h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h and 24h after administration, and plasma is centrifugally separated. Pharmacokinetic tests were performed after the abiraterone acetate containing compositions of the invention were prepared into capsules, and the results are shown in table 9:

TABLE 9 summary of pharmacokinetic parameters

As can be seen from table 9, the oral bioavailability of the abiraterone acetate capsule of example 2 orally administered to beagle dogs on an empty stomach was 136.71% of the oral bioavailability of the abiraterone acetate capsule of comparative example 14. Compared with the comparative example 14, the oral bioavailability of the abiraterone acetate pharmaceutical composition is improved by about 1.36 times, and the variation degree of the peak reaching time, the peak reaching concentration and the absorption level of the drug among individuals is low. When the comparative example 14 abiraterone acetate capsule (containing 50mg of abiraterone acetate) is taken after fasting and high-fat meals, the peak time of the biggee medicine is not obviously different, and the oral bioavailability after meals is only 1.21 times of that before meals; when the abiraterone acetate capsule (containing 50mg of abiraterone acetate) in example 2 is taken after fasting and high-fat meals, the peak time of the beagle medicament is not obviously different, and the oral bioavailability after meals is only 1.13 times of that before meals. Therefore, the abiraterone acetate capsule provided by the invention further reduces the postprandial difference before meals.

As can be seen from Table 9, the postprandial oral bioavailability of the abiraterone acetate capsule provided by the invention is 0.95-1.14 times of that of the abiraterone acetate capsule before meal, which indicates that the postprandial difference before meal is small. Meanwhile, the fasting oral bioavailability of the beagle dog is 130.83-142.55% of the oral bioavailability of the abiraterone acetate capsule in the comparative example 14, which shows that the fasting oral bioavailability of the abiraterone acetate capsule provided by the invention is further improved.

Application example 2

1. Tissue distribution of abiraterone acetate capsules

1.1 administration of drugs

Male rats were randomly grouped, 9 per group. The specific administration mode is as follows:

group 19 male rats were orally administered Zytiga, a dose of 500mg;

36 male rats of groups 2-5 were orally administered 50mg of abiraterone acetate capsules (comparative example 14, example 2, example 6, example 10) prepared according to the present invention.

1.2 sample Collection and processing

The Zytiga group of the original drug was sacrificed 3 rats at each time point 0.5h, 2h, 4h after gavage, while the abiraterone acetate capsule group was sacrificed 3 rats at each time point 0.5h, 2h, 4h after gavage, respectively. Venous blood was collected at 0.5mL, and then rapidly dissected to take out the heart, liver, spleen, lung, kidney, stomach, intestine, sputum, brain, spinal column, spinal fluid, nerve, thymus, lymph node, arterial wall, pancreas, gall bladder, prostate, testis, thyroid, adrenal gland, hypothalamus, pituitary gland, eye, ear, bladder, muscle, skin, leukocyte, bone, cartilage, joint tissue, synovial fluid, and adipose tissue, etc. The tissue taken out was washed with physiological saline to remove blood stain on the surface, and then blotted with filter paper, respectively, and weighed. At the same time, a stool sample in the intestinal tract of the rat needs to be collected and weighed for measuring the unabsorbed medicine amount.

The collected blood sample is anticoagulated by heparin sodium, and is centrifuged for 10min at 3500rpm at 2-8 ℃ within 1h after collection, the separated plasma is stored in a refrigerator at-80 ℃ for testing, and the lymphocytes and the lower layer erythrocytes also need to be recovered to the refrigerator at-80 ℃ for testing.

A certain amount (about 0.2 g) of each tissue sample is taken, 3mL of normal saline is added into each 1g of tissue, the tissue samples are fully stirred and crushed by an electric homogenizer under the ice bath condition, and the tissue samples are placed in a refrigerator at the temperature of minus 80 ℃ for storage and detection. The remaining non-homogenized tissue was recovered and stored in a-80 ℃ freezer.

The whole process of sample collection and treatment is protected from light.

1.3 sample detection

The results of the LC-MS/MS method for detecting the concentration of abiraterone acetate in rat plasma samples, tissue samples (including testis and prostate) and fecal samples are shown in the following tables 10-11.

TABLE 10 rat tissue sample/plasma sample ratio test results

The results show that: as shown in table 10, the abiraterone acetate composition of the present invention (comparative example 14, example 2, example 6, and example 10) has high drug concentration in testis and prostate samples, using the abiraterone acetate concentration in plasma samples as a reference control, which indicates that abiraterone accumulates in testis and prostate, has high concentration in specific local tissues, facilitates entry into the target site, and can produce better drug effect.

TABLE 11 concentration test results of abiraterone in rat feces

The results show that: as shown in table 11, the concentration of abiraterone in the feces of the rats given the abiraterone acetate composition of the present example was significantly lower in the equal weight of the feces than the rats given the control drug 4h after the administration, indicating that more abiraterone in the abiraterone acetate composition of the present example was absorbed.

Claims

1. A composition containing abiraterone acetate is characterized in that: the composition comprises abiraterone acetate and a self-microemulsion system; wherein the mass percentage of the abiraterone acetate to the self-microemulsion system is 4.3-4.8 percent and 95.2-95.7 percent;

the self-microemulsion system comprises an oil phase and an emulsion phase, wherein the mass percentage of the oil phase to the emulsion phase is 30-38% and 62-70%; the oil phase comprises glycerol monolinoleate and medium chain triglycerides; the mass ratio of the glycerol monolinoleate to the medium-chain triglyceride is 2.5-3.63; the emulsion phase comprises polyoxyethylene 40 hydrogenated castor oil and diethylene glycol monoethyl ether; the mass ratio of the polyoxyethylene 40 hydrogenated castor oil to the diethylene glycol monoethyl ether is 1.

2. The composition of claim 1, wherein: the mass percentage of the abiraterone acetate and the self-microemulsion system is 4.4-4.6% and 95.4-95.6%.

3. The composition of claim 1, wherein: the mass percentage of the oil phase and the emulsion phase is 31-35 percent and 65-69 percent.

4. The composition of claim 3, wherein: the mass percentage of the oil phase and the emulsion phase is 32-34 percent and 66-68 percent.

5. The composition of claim 1, wherein: the mass ratio of the glycerol monolinoleate to the medium-chain triglyceride is 2.8-3.5; and/or

The mass ratio of the polyoxyethylene 40 hydrogenated castor oil to the diethylene glycol monoethyl ether is 1.28-2.45.

6. The composition of claim 5, wherein: the mass ratio of the glycerol monolinoleate to the medium chain triglyceride is 3.0-3.4; and/or

The mass ratio of the polyoxyethylene 40 hydrogenated castor oil to the diethylene glycol monoethyl ether is 1.

7. The composition of claim 1, wherein: the composition of each component of the composition is as follows:

abiraterone acetate: 4.3-4.8wt%;

glycerol monolinoleate: 21.4-26.2wt%;

medium chain triglycerides: 6.2-9.6wt%;

polyoxyethylene 40 hydrogenated castor oil: 17.7-19.7wt%;

diethylene glycol monoethyl ether: 42.8-47.8wt%.

8. The composition of claim 1, wherein: the composition of each component of the composition is as follows:

abiraterone acetate: 4.4-4.6wt%;

glycerol monolinoleate: 22.0-26.0wt%;

medium chain triglycerides: 6.8-8.8wt%;

polyoxyethylene 40 hydrogenated castor oil: 18.5-19.5wt%;

diethylene glycol monoethyl ether: 43.0-47.2wt%.

9. The composition according to claim 7 or 8, characterized in that: the composition also comprises an antioxidant and/or a preservative, wherein the antioxidant and/or the preservative accounts for 0.005-0.1% of the total mass of the composition.

10. A capsule comprising the abiraterone acetate-containing composition of any of claims 1-9.

11. Use of a composition comprising abiraterone acetate as claimed in any of claims 1 to 9 in the manufacture of a pharmaceutical formulation for the treatment of prostate cancer.