Abstract: A salt of a quinazoline derivative (N-[4-(3-chlorine-4-fluoroanilino)]-7-(3-morpholinepropanol)-6-(2-fluoroacrylamide)-quinazoline, the structure thereof is as represented by formula I). Compared with a known quinazoline derivative, the salt of the quinazoline derivative has one or more improved properties and at least has better water solubility, wherein a citrate, a benzene sulfonate, and an ethanedisulphonate thereof further have better crystallinity and are not easy to absorb moisture.

Abstract: The present invention provides novel pharmaceutically acceptable salts of a morpholine derivative, including a malate, a tartrate, a hydrochloride, an acetate, and a naphthalene disulfonate thereof, wherein the tartrate has 3 crystal salt forms: crystal form A, crystal form B and dihydrate; the malate, the hydrochloride, and the acetate each have one crystal salt form; the naphthalene disulfonate is amorphous. When compared to the known morpholine derivative free base, the present invention has one or more improved properties, e.g., a better crystalline state, greatly improved water solubility, light stability and thermal stability, etc. The present invention further provides preparation methods for the salts of morpholine derivative and the crystal forms thereof, pharmaceutical compositions and use thereof.

Abstract: A salt of a quinazoline derivative (N-[4-(3-chlorine-4-fluoanilino)]-7-(3-morpholinepropanol)-6-(2-fluoroacrylamide)-quinazoline, the structure thereof is as represented by formula I). Compared with a known quinazoline derivative, the salt of the quinazoline derivative has one or more improved properties and at least has better water solubility, wherein a citrate, a benzene sulfonate, and an ethanedisulphonate thereof further have better crystallinity and are not easy to absorb moisture.

Abstract: A method for preparing an itraconazole formulation including: dissolving a mixture of itraconazole and L-ascorbic acid with a mixed solvent of dichloromethane and methanol, adding a hydroxypropyl methylcellulose and a pluronic F-127 and then dichloromethane into the mixed solvent to obtain a raw material solution; feeding a carbon dioxide into a crystallization autoclave in a supercritical fluid crystallization equipment system through a pressure regulating valve; spraying the solution into the crystallization autoclave via a spray nozzle, separating out composite particles from the solution and collecting the composite particles at a bottom of the crystallization autoclave, and encapsulating the composite particles to obtain a itraconazole formulation with decreased particle size and increased bioavailability.

Abstract: The present invention provides novel pharmaceutically acceptable salts of a morpholine derivative, including a malate, a tartrate, a hydrochloride, an acetate, and a naphthalene disulfonate thereof, wherein the tartrate has 3 crystal salt forms: crystal form A, crystal form B and dihydrate; the malate, the hydrochloride, and the acetate each have one crystal salt form; the naphthalene disulfonate is amorphous. When compared to the known morpholine derivative free base, the present invention has one or more improved properties, e.g., a better crystalline state, greatly improved water solubility, light stability and thermal stability, etc. The present invention further provides preparation methods for the salts of morpholine derivative and the crystal forms thereof, pharmaceutical compositions and use thereof.

Abstract: A method for preparing an itraconazole formulation including: dissolving a mixture of itraconazole and L-ascorbic acid with a mixed solvent of dichloromethane and methanol, adding a hydroxypropyl methylcellulose and a pluronic F-127 and then dichloromethane into the mixed solvent to obtain a raw material solution; feeding a carbon dioxide into a crystallization autoclave in a supercritical fluid crystallization equipment system through a pressure regulating valve; spraying the solution into the crystallization autoclave via a spray nozzle, separating out composite particles from the solution and collecting the composite particles at a bottom of the crystallization autoclave, and encapsulating the composite particles to obtain a itraconazole formulation with decreased particle size and increased bioavailability.