16 results about "Posaconazole" patented technology

The invention provides a posaconazole ethosome and a preparation method thereof, posaconazole is encapsulated in ethosome, and the posaconazole ethosome is composed of the following components by weight: 0.1-5% of posaconazole, 0.1-5% of posaconazole, 0.1-5% of posaconazole, 0.1-5% of posaconazole, and the balance of ethanol. 1-8% of phospholipid; 0%-0.5% of cholesterol; 20%-45% of ethanol; 0-0.1% of an antioxidant; 0%-0.5% of a nonionic surfactant; and 40.9 to 78.9 percent of water. The invention has the characteristics of high encapsulation efficiency, uniform particle size distribution and no irritation to skin. And the ethosome can load both water-soluble drugs and fat-soluble drugs, and has the advantages of simple composition, high encapsulation efficiency, uniform particle size distribution, no skin irritation, simple preparation and the like.

A gastro-resistant high-strength unit dosage form includes a solid solution prepared by hot-melt extrusion, whereby the solid solution contains 300 mg posaconazole and an enteric polymer in a specific weight ratio. The unit dosage form may be a capsule or an optionally film-coated tablet.

The invention relates to application of azole drugs in preparation of antifungal drugs, and belongs to the technical field of research and development of antifungal drugs. According to the application of the glycyrrhetinic acid combined with the azoles in preparation of the antifungal drugs, the glycyrrhetinic acid combined with the itraconazole, the voriconazole and the posaconazole shows a good synergistic effect or antagonistic effect on aspergillus, ectobottle dermatitis, candida and cryptococcus neoformans, and the application of the glycyrrhetinic acid combined with the itraconazole, the voriconazole and the posaconazole in preparation of the antifungal drugs is disclosed. And a research and development direction is provided for preparing medicines for resisting aspergillus, ectobottle dermatitis, candida and cryptococcus neoformans.

The present disclosure provides for methods of treating a patient with a CYP3A4 substrate drug, wherein the patient is treated with posaconazole. In some embodiments, the patient stops posaconazole treatment, waits for at least 3 days, and then is treated with the CYP3A4 substrate drug as soon as it is safe to do so. In some embodiments, treatment with the CYP3A4 substrate drug is delayed for about 3-42 days after stopping posaconazole. In some embodiments, the patient is treated with a reduced dose of the CYP3A4 substrate drug for about 3-42 days.

The invention discloses an in-vitro dissolution method of a posaconazole enteric-coated tablet, which is characterized in that a Tween-80 (TWEEN-80) surfactant is added into a dissolution medium, so that the solubility of the posaconazole enteric-coated tablet in a phosphate buffer solution is remarkably improved, the phenomenon that a solution in a dissolution cup is not uniform is solved, the jump point phenomenon of a dissolution curve is eliminated, and the dissolution rate of the posaconazole enteric-coated tablet is improved. When a phosphate buffer solution added with a certain amount of surfactant is used as a dissolution medium, the accumulated dissolution amount at each time point is stable, the dissolution curve is smooth, the detection result is accurate and reliable, the repeatability and predictability of the dissolution test are remarkably improved, and a more reliable detection method is provided for the initial stage of drug research and development and quality control.

One embodiment of the present invention provides a posaconazole-containing solid dispersion that suppresses the delayed dissolution of posaconazole during the storage period after manufacturing or the period until administration of a posaconazole-containing formulation. Alternatively, one embodiment of the present invention provides a posaconazole-containing formulation in which the delayed dissolution of posaconazole during the storage period after manufacturing or the period until administration is suppressed. [Solution] A posaconazole-containing solid dispersion according to one embodiment of the present invention comprises posaconazole, hypromellose acetate succinate, and hydroxypropyl cellulose having a viscosity of 6 mPa·s or more and 10 mPa·s or less in a 2% aqueous solution at 20°C and an average molecular weight of 140,000.

The present disclosure relates to a method for preparing a compound as an intermediate for synthesizing the drug posaconazole and the intermediate compounds prepared thereby. The method for preparing a compound of Formula I provided in the present disclosure comprises: firstly reacting 4-(2,4-difluorophenyl)pent-4-enoate or its reduction product 4-(2,4-difluorophenyl)pent-4-enal as a starting material with formaldehyde or paraformaldehyde in the presence of a chiral catalyst, and then subjecting the reaction product to a characteristic oxidation, an esterification, a halogenation and cyclization reaction, finally a hydrolysis and an acid treatment. The preparation method of the present disclosure has advantages such as mild reaction conditions, simple reaction process, and high overall yield and high purity of target products, and thus is suitable for industrial production.

The present disclosure provides a liquid composition comprising posaconazole, and a preparation method and use thereof. The liquid composition comprises posaconazole, a cyclodextrin, a dilution stabilizer, an antioxidant, and an acidic pH regulator. The dilution stabilizer comprises hydroxypropyl cellulose and / or hydroxypropyl methylcellulose, and the cyclodextrin is present in an amount of 25% to 45% (w / v), based on the total volume of the liquid composition. The liquid composition can increase an oral bioavailability of posaconazole, mitigate an impact of food on bioavailability of posaconazole, and improve patient compliance.

The application provides a synthesis method of posaconazole halogenated cyclic intermediate, which comprises the following steps: carrying out halogenation reaction on a raw material intermediate shown in formula (1) and a halogenating reagent in an organic solvent in the presence of an acidic substance, so as to obtain a posaconazole halogenated cyclic intermediate shown in formula (2). The application also provides a synthesis method of posaconazole. The synthesis method provided by the application activates the halogenating reagent by using a cheap acidic substance and carries out the halogenation reaction under low-temperature conditions, so that the target product has the advantages of high yield, high diastereoselectivity and the like, the process is simple and convenient to operate, post-treatment is simple, the synthesis efficiency is obviously improved, the synthesis cost is reduced, the synthesis method provided by the application has great potential for industrialized production, has strong industrial practicability, and has important significance for expanding the production and application of posaconazole.

This invention discloses a novel use of posaconazole to enhance the immune response in the immunotherapy of breast cancer. Specifically, this invention provides a drug combination comprising posaconazole and a PD-L1 inhibitor. The effects of this invention are: (1) using posaconazole to prepare a drug for treating breast cancer, especially triple-negative breast cancer (TNBC), achieving "repurposing of an old drug"; (2) clarifying its core mechanism of action, clarifying that the anti-tumor effect of clinically commonly used doses of posaconazole depends on the host immune system, rather than traditional direct cytotoxicity, specifically by inhibiting CYP11A1 and other related enzymes in the tumor, thereby reducing immunosuppressive steroid hormones, providing a new drug and target for tumor immunotherapy; (3) providing a technical solution for the combined treatment of posaconazole and PD-L1 inhibitors (such as anti-PD-L1 antibodies), further enhancing anti-tumor immunity and improving the treatment effect of TNBC.

The application relates to the application of azole drugs in the preparation of antifungal drugs and belongs to the technical field of antifungal drug research and development. The application of glycyrrhetic acid combined with azole drugs in the preparation of antifungal drugs discloses that glycyrrhetic acid combined with itraconazole, voriconazole and posaconazole shows good synergistic effect or antagonistic effect on aspergillus, exophiala dermatiditis, candida and new cryptococcus, and provides a research and development direction for preparing drugs for resisting aspergillus, exophiala dermatiditis, candida and new cryptococcus.

This disclosure provides a liquid composition containing posaconazole, a method for preparing the same, and its uses. The liquid composition comprises posaconazole, cyclodextrin, a dilution stabilizer, an antioxidant, and an acidic pH adjuster. The dilution stabilizer comprises hydroxypropyl cellulose and / or hydroxypropyl methylcellulose. The cyclodextrin comprises 25% to 45% of the total mass of the liquid composition. This liquid composition can improve the oral bioavailability of posaconazole, reduce the influence of food on bioavailability, and improve patient compliance.

The present disclosure relates to a method for preparing a compound as an intermediate for synthesizing the drug posaconazole and the intermediate compounds prepared thereby. The method for preparing a compound of Formula I provided in the present disclosure comprises: firstly reacting 4-(2,4-difluorophenyl) pent-4-enoate or its reduction product 4-(2,4-difluorophenyl) pent-4-enal as a starting material with formaldehyde or paraformaldehyde in the presence of a chiral catalyst, and then subjecting the reaction product to a characteristic oxidation, an esterification, a halogenation and cyclization reaction, finally a hydrolysis and an acid treatment. The preparation method of the present disclosure has advantages such as mild reaction conditions, simple reaction process, and high overall yield and high purity of target products, and thus is suitable for industrial production.

According to the preparation method of the posaconazole key intermediate, 2, 4-difluorobromobenzene serves as a raw material, the target compound (I) is obtained through the Grignard reaction, elimination and substitution reactions, the raw materials are easy to obtain and low in price, the Grignard reaction is mature, the reaction conditions are mild, the yield is high, reagents which have great harm to the environment are not used, and the preparation method is more environmentally friendly and suitable for industrial production. The method is suitable for large-scale industrial production.

This invention belongs to the field of organic synthesis technology and relates to a method for preparing the key chiral intermediate (S)-4-(2,4-difluorophenyl)-2-(hydroxymethyl)pent-4-en-1-yl isobutyrate of posaconazole. In an electrochemical cell, 1-[1-(bromomethyl)vinyl]-2,4-difluorobenzene and methyl 2-bromo-3-isobutyryloxypropionate are reacted in the presence of a chiral nickel catalyst, followed by reduction to obtain the target product. This invention achieves asymmetric coupling of allyl and alkyl radicals through an electrochemical redox process catalyzed by a chiral nickel catalyst, constructing the core carbon skeleton and chiral center in one step. This avoids the cumbersome operations of multi-step functional group transformation and protection, and the target product exhibits high enantioselectivity and high overall yield, significantly reducing production costs and making it suitable for industrial production.