41 results about "Abiraterone" patented technology

The invention provides an abiraterone derivative as well as a preparation method and application thereof. The abiraterone derivative has a chemical structural formula as shown in a formula (I). The abiraterone derivative disclosed by the invention can be converted into an active substance abiraterone in vivo, has the characteristics of good absorption, good plasma stability, ideal permeable membrane transport capability, good druggability and high safety, and can be used for treating diseases related to excessive androgen. # imgabs0 #

Sustained-release abiraterone prodrug formulations, methods, and kits for parenteral administration to a human subject having a sex hormone-dependent or androgen receptor driven disease or disorder, such as a sex hormone-dependent benign or malignant disorder such as prostate cancer, an androgen receptor driven cancer, and / or a syndrome due to androgen excess.

The present disclosure relates to methods of treating PTEN-deficient metastatic hormone- sensitive prostate cancer (mHSPC) in patients in need thereof, the methods comprising administering to the patients a combination comprising capivasertib or a pharmaceutically acceptable salt thereof; and abiraterone or an ester prodrug thereof, or a pharmaceutically acceptable salt thereof.

The present disclosure relates to methods of treating prostate cancer in a subject comprising administering to the subject (a) an androgen receptor inhibitor and (b) an embryonic ectoderm development (EED) inhibitor, including those in which prostate cancer has been determined to be resistant to one or more androgen receptor signaling inhibitors (ARSIs), including (abiraterone).

A method for preparing abiraterone acetate and an intermediate thereof are provided. In the method, in an organic solvent, in the presence of a metal catalyst, reacting a 3-site protected 17-hydroxy ester androst-5,16-diene-3β-hydroxy (ester) with a 3-substituted pyridine derivative to obtain abiraterone acetate or the intermediate thereof.

Provided are pharmaceutical compositions which include an amorphous solid dispersion comprising i) a lipophilic active pharmaceutical ingredient such as abiraterone, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, or vilazodone or a salt thereof, ii) a hydrophilic polymer, iii) optionally a surfactant, iv) optionally an adsorbent, and v) optionally an acid. Also described are methods for preparing such pharmaceutical compositions and treating a subject in need thereof. In one aspect, disclosed herein is an amorphous solid dispersion comprising an active pharmaceutical ingredient.

The invention belongs to the technical field of crystal form drug molecules, and particularly relates to salts of abiraterone derivatives, in particular to glutarate of L-valine abiraterone. The glutarate of L-valine abiraterone provided by the invention has characteristic peaks at the positions of 8.2 + / -0.2 degrees, 8.9 + / -0.2 degrees, 9.9 + / -0.2 degrees, 16.5 + / -0.2 degrees, 17.0 + / -0.2 degrees, 17.8 + / -0.2 degrees and 19.8 + / -0.2 degrees in an X-ray diffraction spectrum represented by 2 theta. The glutarate has improved dissolution and dissolution performance, can play a therapeutic role more effectively, and is good in stability, small in adhesiveness and convenient to store and process.

The invention discloses an abiraterone acetate self-nanoemulsion liquid-filled capsule as well as a preparation method and application thereof. The abiraterone acetate self-nanoemulsion liquid-filled capsule is good in self-nanoemulsion effect, controllable in preparation quality and remarkable in killing effect on prostate cancer cells, the bioavailability of the capsule is improved by 12.54 times compared with that of commercially available tablets, the influence of food on the bioavailability of drugs is reduced, the limitation of abiraterone tablets in clinical application is expected to be overcome, and the capsule is worthy of popularization and application. The research has important scientific significance and potential clinical application value.

The utility model relates to the technical field of intermediates, and discloses an abiraterone intermediate AB production device which comprises a reaction cylinder, a heating hollow ring is arranged on the outer side of the reaction cylinder, a plurality of heating rings are arranged in the heating hollow ring, a top cover cylinder is arranged at the top of the reaction cylinder, and a top cover is arranged at the bottom of the top cover cylinder. The bottom of the top cover cylinder is fixedly connected with a flange, the top cover cylinder is fixedly connected with the reaction cylinder through the flange, and the left side of the top of the top cover cylinder is communicated with a feeding pipe. The reaction cylinder is divided into four areas through the partition plate, the direct-current motor drives the partition plate and drives the T-shaped supporting plate to rotate, the stirring assembly enables the cylinder to have different rotating speeds in different areas, and after the cylinder rotates by one circle, the second electric valve is opened, and reaction mixed liquid is discharged. Therefore, the production of the abiraterone intermediate AB is automatically completed.

Disclosed is abiraterone or a pharmaceutically acceptable salt thereof in a therapeutically effective amount for use in the treatment of Cushing's disease in dogs, wherein the pharmaceutically acceptable salt is preferably abiraterone acetate.

The invention relates to the field of pharmaceutical preparations and pharmaceutical chemistry, belongs to the technical field of oral delivery of antitumor drugs, and particularly relates to an abiraterone lipophilic prodrug and application thereof. The prodrug meets the following general formula: AB-O-C (= O)-(CH2) m-S-S-(CH2) m-C (= O)-O-R, the prodrug significantly improves the fat solubility and intestinal absorption capacity of abiraterone, can be absorbed through a chylomicron-mediated lymph transport pathway, and releases a parent drug in a tumor cell high-reducibility environment. The SNEDDS preparation containing the prodrug can form a particle size of 1t in vivo; the O / W type nano emulsion droplet with the size of 100 nm can significantly improve the oral bioavailability of abiraterone and inhibit the growth of prostatic cancer tumors, and has a good application prospect.

The application discloses an abiraterone derivative and a preparation method thereof. The abiraterone derivative has a structure as shown in a general formula (I). The abiraterone derivative has high bioavailability and good tumor inhibition effect, and has a high drug prospect.

This invention relates to a method of treating prostate cancer comprising administering a compound of Formula (I) or a salt thereof in combination with either abiraterone or enzalutamide.

The present disclosure relates to a combination of abiraterone acetate and niraparib, free-dose and fixed-dose combinations of abiraterone acetate and niraparib, and methods of treatment of prostate cancer with said combinations.

The present application relates to the technical field of pharmaceutical preparation, and in particular to an abiraterone acetate enteric microcapsule and a preparation method thereof. The present application uses an emulsion diffusion method to prepare abiraterone acetate nanocapsules, then uses an enteric material to load the abiraterone acetate nanocapsules, and finally uses a spray drying technology to prepare abiraterone acetate oral enteric microcapsules. Through pharmacokinetic tests of a rat chylomicron blocking model, it is verified that the abiraterone acetate enteric microcapsules prepared by the present application are absorbed by the lymphatic pathway in the small intestine, so it is proved that the present application can enhance the permeability and solubility of abiraterone acetate in the body, improve the oral bioavailability thereof in the body, the preparation method is simple and controllable, has good repeatability, the particle size of the prepared nanocapsules is 182.3±5.7 nm, the Zeta potential is-15.0±1.1 mV, and the encapsulation rate is 92.4±1.7%.

The invention relates to the technical field of medicine detection, and discloses a method for detecting N-oxide impurities in abiraterone acetate medicine, which comprises the following steps: mixing an N-oxide impurity reference substance with acetonitrile to obtain a reference substance solution; the method comprises the following steps: mixing an abiraterone acetate medicine to be detected with acetonitrile to obtain a test solution; detecting the reference substance solution and the test solution by adopting a high performance liquid chromatography to obtain a chromatogram; in the detection process of the high performance liquid chromatography, mobile phases comprise a mobile phase A and a mobile phase B, the mobile phase A is acetonitrile, and the mobile phase B is water; and (4) analyzing by adopting an external standard method according to the chromatogram to obtain the content of the N-oxide impurity in the abiraterone acetate medicine. The method is high in detection sensitivity on the N-oxide impurities in the abiraterone acetate tablets, the method is good in durability, the N-oxide impurities in the abiraterone acetate tablets can be effectively controlled, and the controllability of the quality of the abiraterone acetate tablets is improved.

The invention discloses an abiraterone borane carrying agent with prostatic cancer targeting property as well as a preparation method and application of the abiraterone borane carrying agent. The abiraterone borane compound comprises abiraterone borane and abiraterone acetate borane. According to the embodiment of the invention, based on abiraterone acetate and prostatic cancer targeting and safety of abiraterone, a borane group is introduced into structures of abiraterone acetate and abiraterone acetate, and a novel boron carrying agent is obtained and is used for BNCT treatment of prostatic cancer. The novel boron carrying agent not only retains the CYP17 enzyme inhibitory activity of abiraterone and abiraterone acetate, but also provides the possibility of targeting prostate cancer cells for BNCT by introducing a 10B isotope. Through the innovative medicine design, the curative effect and selectivity of BNCT in prostatic cancer treatment can be remarkably improved, damage to normal tissue is reduced, and a safer and more effective treatment choice is provided for prostatic cancer patients.

Sustained release abiraterone prodrug formulations, methods, and kits for parenteral administration to human subjects suffering from a sex hormone dependent or androgen receptor driven disease or disorder, e.g., a sex hormone dependent benign or malignant disorder, e.g., prostate cancer, androgen receptor driven cancer, and / or syndromes resulting from androgen excess.

Disclosed in the present invention are an abiraterone derivative, a pharmaceutical composition, and a preparation method therefor and the use thereof. Provided in the present invention is an abiraterone derivative as represented by formula (1) or formula (2), or a pharmaceutically acceptable salt thereof. In contrast to existing abiraterone derivative structures in which each molecule contains one abiraterone molecule, the compound of the present invention contains two abiraterone molecules per molecule. The compound of the present invention has long-acting sustained-release characteristics, can be injected subcutaneously or intramuscularly, maintains the blood drug level for 12 weeks (3 months) or longer, and is used for treating prostate cancer.

The invention belongs to the technical field of crystal form medicine molecules, and particularly relates to a p-toluenesulfonic acid crystal form of L-valine abiraterone and a preparation method of the p-toluenesulfonic acid crystal form. In the p-toluenesulfonic acid crystal form of L-valine abiraterone provided by the invention, the molar ratio of L-valine abiraterone to p-toluenesulfonic acid to water is 1: 1: 2, and an X-ray diffraction pattern represented by 2 theta has characteristic peaks at the positions of 11.9 + / -0.2 degrees, 12.9 + / -0.2 degrees, 15.4 + / -0.2 degrees, 17.5 + / -0.2 degrees and 21.5 + / -0.2 degrees. The obtained crystal form has improved stability, solubility and flowing property, is suitable for manufacturing and application of pharmaceutical preparations, and is expected to promote design of abiraterone preparations and clinical application.

The invention provides a temperature-sensitive hydrogel for prostate local drug delivery and a preparation method thereof. The core components of the temperature-sensitive hydrogel comprise a temperature-sensitive carrier compounded by a polylactic acid-glycolic acid-polyethylene glycol triblock copolymer and modified chitosan, targeted active components such as abiraterone and the like and a composite bacteriostatic agent, and a biological adhesion and transdermal enhancer is added; the hydrogel is a sol at normal temperature, is convenient for administration, is rapidly gelatinized at 35-37 DEG C to realize local retention, has excellent biological adhesion and antibacterial properties, is stable and long-acting in drug release, and has an accumulative release rate of 86-92% in 96 h. The preparation process is stable and controllable, is suitable for treating diseases such as prostatic cancer and prostatitis, can improve the bioavailability of drugs and reduce side effects, and has important clinical application value.

The present disclosure provides a double-stranded RNA (dsRNA) inhibitor for inhibiting expression of human serine / threonine kinase 1 (AKT1), a lipid composition comprising the dsRNA inhibitor, and uses thereof. The present disclosure also provides the use of a dsRNA inhibitor or a lipid composition comprising the dsRNA inhibitor in combination with abiraterone for the treatment of cancer.

Sustained release abiraterone prodrug formulations, methods, and kits are provided for parenteral administration to a subject suffering from a sex hormone dependent benign or malignant condition, such as prostate cancer, syndrome caused by androgen hyperactivity, and / or syndrome caused by glucocorticoid hyperactivity, such as hypercorticoinemia.

The invention belongs to the technical field of raw material medicine synthesis, and discloses a process for preparing abiraterone by a one-pot method. The process for preparing abiraterone by the one-pot method comprises the following steps: mixing an aprotic ether solvent, 3-bromopyridine, iodine, magnesium and a catalyst for reaction to obtain a Grignard reagent of the 3-bromopyridine; mixing a Grignard reagent of 3-bromopyridine, a raw material 3, triphenylphosphine, a metal catalyst and an aprotic ether solvent, and reacting to obtain an intermediate 2 solution; and mixing the intermediate 2 solution with an acid solution, and then adjusting the pH value to obtain abiraterone. The process successfully realizes a method for preparing abiraterone by a Grignard reaction, a Kumada reaction, a hydrolysis reaction and a neutralization reaction through a one-pot method, abiraterone is produced from the raw material 3-bromopyridine and the raw material 3 in one step, the requirement of continuous production is met, the requirement of green chemistry is met, pollution is reduced, the yield is increased, and the cost is reduced.

The present disclosure relates to a pharmaceutical product having at least one batch indication, wherein the pharmaceutical product comprises niraparib and abiraterone acetate.

The invention discloses a high performance liquid chromatography analysis method for determining abiraterone-related impurities in abiraterone oral emulsion. The chromatographic conditions are as follows: the chromatographic column is an octadecylsilane bonded silica gel column, the acetate buffer-mobile phase B volume ratio is (45:55) to (55:45) as mobile phase A, the methanol-acetonitrile volume ratio is (1.5:8.5) to (2.5:7.5) as mobile phase B, gradient elution, the concentration of acetate buffer is 0.005 to 0.015 mol / L, the column temperature is 35 to 45 ° C, the flow rate is 1.1 to 1.3 ml / min, the detection wavelength is 254 nm, and the injection volume is 10 μl. The assay method of the present invention can quickly and accurately detect the content of abiraterone-related impurities in abiraterone oral emulsion, is simple to operate, has good reproducibility, is highly sensitive, can better control abiraterone oral emulsion intermediates and formulation impurities, and provides a guarantee for formulation process optimization.

A drug composition containing abiraterone acetate, and a preparation method therefor and an application thereof. Excipients thereof comprise at least one oil phase, at least one emulsifier, and at least one co-emulsifier. The dug composition can obviously improve the bioavailability and the stability of a preparation. The drug composition can be further prepared as capsules.

Sustained-release abiraterone prodrug formulations, methods, and kits for parenteral administration to a subject having a sex hormone-dependent benign or malignant disorder such as prostate cancer, an androgen receptor driven cancer, a syndrome due to androgen excess, and / or a syndrome due to glucocorticoid excess such as hypercortisolemia.