112 results about "Olaparib" patented technology

The invention relates to the field of a pharmaceutical preparation, and in particular discloses an olaparib solid dispersion preparation and a preparation method thereof. The olaparib solid dispersion preparation consists of olaparib, povidone, a special lubricating agent, a special disintegrating agent and a thinner. According to the olaparib solid dispersion preparation disclosed by the invention, povidone, replacing the existing copovidone, is used as a matrix polymer, and appropriate auxiliary materials are added, so that the povidone, as the matrix polymer of the olaparib solid dispersion preparation, is wide in source, low in cost and clear in quality standard in accordance with Chinese Pharmacopoeia; meanwhile, the dissolution effect, bioavailability and stability of the preparation are guaranteed; and the industrial production of the olaparib solid dispersion preparation is facilitated.

The invention discloses a preparation method of Olaparib and an analogue of the Olaparib. 2-fluoro-5-formyl benzoic acid is taken as a raw material and reacts with 1-substitutent piperazine to produce 3-(4-substitutent)piperazine-1-carbonyl)-4-fluorobenzalde which reacts with (3-oxo-1,3-dihydro-isobenzofuran-1-yl)dialkyl phosphate to produce 1-(substitutent)-4-[5-(3-oxo-3H-isobenzofuran-1-yl-methylene)-2-fluorobenzoyl]piperazine, then the 1-(substitutent)-4-[5-(3-oxo-3H-isobenzofuran-1-yl-methylene)-2-fluorobenzoyl]piperazine reacts with hydrazine hydrate to produce the Olaparib (Ia,R=cyclopropyl formyl) and the analogue (Ib,R=BOC) of the Olaparib; or 3-(4-substitutent)paperazine-1-carbonyl)-4-fluorobenzalde reacts with phthalide to produce 1-(substituent)-4-[5-(2,3-dihydro-1,3-dioxo-1H-indene-2-yl)-2-fluorobenzoyl]piperazine which reacts with the hydrazine hydrate to produce the Olaparib (Ia,R=cyclopropyl formyl) and the analogue (Ib,R=BOC) of the Olaparib.

The invention discloses a preparation method for olaparib. The preparation method comprises the following steps: subjecting 4-(4-fluoro-3-(piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one, a condensing agent, cyclopropanecarboxylic acid, alkali and a polar organic solvent to a reaction at 0 to 120 DEG C for 2 to 8 h; adding water; allowing a solid to be precipitated; and carrying out pumping filtration, washing and drying so as to obtain olaparib. According to the invention, cyclopropanecarboxylic acid is used as a raw material; reaction conditions are mild; operational safety is good; organic solvents like dichloromethane is not needed for aftertreatment; separation and purification steps are simple; the yield of olaparib is high, as high as 92% or above; raw materials are easily available; the method is simple; side reactions are few; the chromatographic purity of olaparib is high; industrial scale-up production can be easily implemented; and the method has good industrial application prospects.

The invention relates to olaparib and urea eutectic and a preparation method thereof and particularly provides a eutectic form A, an X-ray powder diffraction of the crystal form shows characteristic peaks at 17.4 DEG +/- 0.2 DEG, 20.7 DEG +/- 0.2 DEG and 10.5 DEG +/- 0.2 DEG of value 2theta.The eutectic has better stability, lower hygroscopicity and higher solubility than existing olaparib free base crystal forms and is of significant value to the optimization and development of its drugs in future.

Methods and systems for identifying a cancer patient suitable for treatment with a PARP inhibitor. A 6-gene, 7-gene and 8-gene predictor panels of genes that are predictive of patient resistance or sensitivity to PARP inhibitors such as Olaparib.

The present invention relates to co-precipitates of olaparib and an ionic polymer and pharmaceutical composition containing the co-precipitates. Further, the present invention relates to a method of treating disorders in a patient in need thereof, comprising administering a therapeutically effective amount of said composition.

Tumor-Treating Fields elicit a conditional vulnerability to PARP inhibitors (e.g., Olaparib) in certain cancer cells such as non-small cell lung cancer (NSCLC) cell lines. This conditional vulnerability is exploited in a method of killing cancer cells that comprises delivering a PARP inhibitor to the cancer cells and applying an alternating 80-300 kHz electric field to the cancer cells. At least a portion of the applying step is performed simultaneously with at least a portion of the delivering step. In some embodiments, an additional step of treating the cancer cells with a radiation therapy is added to the method. In some embodiments, the frequency of the alternating electric field is between 100 and 200 kHz.

The invention relates to an olaparib compound refining method. The method includes synthesis of a crude olaparib product and refining of olaparib. Refining includes steps: 1) adding ethyl acetate petroleum ether mixed liquid and the crude olaparib product into a reaction bottle, slowly heating to 50-55 DEG C, performing heat-preservation stirring for 20min, heating to 70-75 DEG C, stirring, and dissolving the crude product to obtain crude product solution; adding activated carbon into the crude product solution, decolorizing, filtering and collecting filtrate; 2) slowly cooling the filtrate to 20-25 DEG C, keeping the temperature and stirring; 3) cooling the filtrate to 0 DEG C or below, controlling a stirring speed at 15r/min, adding seed crystal, controlling the temperature and the stirring speed to grow the crystal for 1.5h, filtering, flushing a filter cake with a small quantity of ethyl acetate petroleum ether mixed liquid, and drying to obtain a refined olaparib product. The refining method has advantages of simple conditions, reduction of olaparib disubstituted substances, high product purity and the like.

The invention discloses an olaparib and maleic acid cocrystal and a preparation method thereof. The molar ratio of olaparib to maleic acid in the cocrystal is 1:1, and an X-ray powder diffraction pattern of the cocrystal has characteristic peaks when the 2theta values are 5.1+/-0.2 degrees, 9.8+/-0.2 degrees, 13.7+/-0.2 degrees, 16.0+/-0.2 degrees, 17.7+/-0.2 degrees and 20.0+/-0.2 degrees. The cocrystal preparation method provided by the invention is simple in process, easy to control the crystallization process, good in reproducibility and suitable for industrial production. Compared with olaparib free alkali, the cocrystal has higher apparent solubility, and is beneficial to improving the oral absorption efficiency of olaparib.

The invention belongs to the field of biological medicines, and particularly relates to an application of CDCA8 in the preparation of a drug for treating ovarian cancer. The invention provides an application of a reagent for inhibiting CDCA8 gene expression or inhibiting a CDCA8 gene expression product in the preparation of a drug for treating ovarian cancer and/or inhibiting proliferation, invasion and migration of ovarian cancer cells and at the same time promoting ovarian cancer cell cycle arrest and apoptosis. In addition, the inhibition of the expression of CDCA8 or the inhibition of theCDCA8 gene expression product can enhance the sensitivity of ovarian cancer cells to chemotherapeutic drugs cisplatin and olaparib by adjusting the cell cycle and inhibiting DNA damage repair. A new thought is provided for screening drugs for treating ovarian cancer, especially serous ovarian cancer, and a new method is provided for enhancing the sensitivity to traditional ovarian cancer chemotherapeutic drugs.

The invention belongs to the technical field of medicine, and discloses an olaparib dihydrate and a preparation method thereof. Characteristic diffraction peaks are displayed at 6.75 DEG, 7.04 DEG, 9.16 DEG, 10.53 DEG, 15.20 DEG, 17.46 DEG, 20.68 DEG, 22.21 DEG, 27.43 DEG, 28.62 DEG, 29.30 DEG, 35.23 DEG and 37.14 DEG of X-ray powder diffraction spectra of the crystalline compound expressed at diffraction angles of 2Theta+/-0.2 DEG, and the X-ray powder diffraction spectra measured by the aid of Cu-K alpha rays are shown as a graph 1 and are totally different from X-ray powder diffraction spectra in the prior art. The experiment proves that the dissolvability of the olaparib dihydrate is obviously increased. The invention also discloses the preparation method of the olaparib dehydrate, the preparation method is simple and easy to carry out, the yield and purity are high, the reaction condition is mild, and the method is suitable for large scale production. A dissolution rate and the stability of the capsule prepared by the olaparib dihydrate are obviously increased, and the capsule is very suitable for clinical application.

The invention relates to a preparation method of medicine Olaparib for treating ovarian cancer. The preparation method comprises the following steps of 1, adding Olaparib crude product into mixed solvent of dimethyl carbonate and isopropyl ether, slowly heating to 45-50 DEG C, keeping warm and stirring for 30min, continuously raising to 60-65 DEG C, stirring until the crude product is dissolved to acquire crude production solution; 2, adding active carbon, into the crude product solution, decoloring, filtering and collecting filtrate; 3, slowly cooling to reduce the temperature of the filtrate to 30-35 DEG C, keeping warm and stirring; and 4, further cooling the filtrate to be 5 DEG C and below, controlling a stirring speed to be 150 turns/min, adding seed crystal, filtering after controlling the temperature and the steering speed to grow the crystal for 2h, washing a filter cake with a small amount of mixed solvent of dimethyl carbonate and isopropyl ether, and drying to acquire the Olaparib. The preparation method provided by the invention is simple in technology, high in yield and purity, particularly significantly reduced in bisubstituted product, and meanwhile an applicant is surprised to find that the prepare Olaparib is significantly reduced in hygroscopicity.

Disclosed arc PARP-1 inhibitors, which can be ¹⁸P-labeled for use as tracers in positron emission tomographic (PET) imaging. Further disclosed are methods of synthesis. Of the compounds synthesized, 2-[p-(2-Fluoroethoxy)phenyl]-1,3,10-triazatricyclo[6.4.1.0^4,13]trideca-2,4(13),5,7-tetraen-9-one (12) had the highest inhibition potency for PARP-1 (IC₅₀=6.3 nM). Synthesis of [¹⁸F]-12 is disclosed under conventional conditions in high specific activity with 40-50% decay-corrected yield, MicroPET imaging using [¹⁸F]-12 in MDA-MB-436 tumor-bearing mice demonstrated accumulation of [¹⁸F]-12 in a tumor. Binding, can be blocked by olaparib. The compounds have utility for tumor imaging.

The invention belongs to the technical field of medicines, discloses an antineoplastic drug hydrate and a preparation method thereof, and particularly discloses an Olaparib hydrate and a preparation method thereof. An X-ray powder diffraction pattern, represented by the diffraction angle of 2theta+/-0.2 degrees, of the Olaparib hydrate shows characteristic diffraction peaks at 2.228 degrees, 4.309 degrees, 7.125 degrees, 14.613 degrees, 19.134 degrees, 24.672 degrees, 25.448 degrees, 26.317 degrees, 32.115 degrees, 34.451 degrees and 36.228 degrees, the X-ray powder diffraction pattern obtained by using Cu-Kalpha rays for measurement is shown in figure 1, and the Olaparib hydrate is completely different from the prior art. It is surprisingly found through experiments that the solubility of the Olaparib hydrate is remarkably improved. The preparation method of the antineoplastic drug hydrate is also disclosed and simple and easy to operate, the yield and the purity are high, the reaction condition is mild, and the antineoplastic drug hydrate is suitable for large-scale production. The dissolution and stability of capsules made from the Olaparib hydrate are significantly improved, and the Olaparib hydrate is very suitable for clinical application.

The invention discloses an olaparib amorphous compound, and a preparation method thereof. The x-ray powder diffraction pattern of the olaparib amorphous compound is represented by formula 1. The preparation method comprises following steps: olaparib raw material is heated directly under insert gas protection until complete fusion is realized; an obtained molten product is delivered into a clean metal container, or added into stirred ice-water mixture, or is cooled to room temperature in 2 to 3h directly so as to obtain the olaparib amorphous compound, wherein the temperature in the clean metal container is controlled to be room temperature, or the clean metal container is subjected to precooling until the temperature is lower than room temperature. The olaparib amorphous compound is high in solubility and stability; solvent residue amount is extremely low; the olaparib amorphous compound possesses significant importance in preparation, storage, and applications of subsequent preparations; the preparation method is simple; yield is high; quality is stable; production period is short; and large-scale production is convenient to realize.