72 results about "Ulipristal acetate" patented technology

The invention provides a new synthesis method of a progesterone receptor regulating agent ulipristal acetate. The method has simple and short steps and mild conditions and is easy to operate, the obtained product has low cost, high yield and high purity, and the method is easy to amplify and is suitable for industrial production.

The invention provides a method for purifying ulipristal serving as a synthetic progesterone receptor regulator. By adopting the method, high-purity ulipristal acetate can be obtained by quickly removing various impurities. The method is easy and convenient to operate, high in yield and suitable for industrial production.

The invention discloses a polycrystal form A1 and a polycrystal form A2 of ulipristal acetate (formula I) free of solvate and a preparation method, a pharmaceutical composition and medical application of the polycrystal forms. By verification of melting point, X-ray diffraction powder spectrum (XRD), infrared spectrum (IR), differential thermal analysis spectrum (DSC) and thermogravimetric spectrum (TG), the polycrystal form A1 and polycrystal form A2 of ulipristal acetate prepared by the method disclosed by the invention are extremely stable to temperature, illumination and humidity, and favorable to long-term storage; the used crystallizing solvent is safe and easy to remove; the obtained polycrystal form A1 and the polycrystal form A2 can be directly used for preparation processing; and the preparation method is simple in operation and suitable for industrial production. The formula I is shown in the description.

The invention relates to a ulipristal acetate preparation and a preparation method thereof, and particularly relates to a ulipristal acetate dispersible tablet with improved dissolution rate and a preparation method thereof. In order to solve the problem that the ulipristal acetate tablet in the prior art is low in dissolution rate and bioavailability and affects emergency contraception effects, the invention provides the ulipristal acetate dispersible tablet. The ulipristal acetate dispersible tablet is prepared from a premix compound of ulipristal acetate and a disintegrating agent and a excipient, wherein the content of ulipristal acetate is 1-30%(w/w) and accounts for 50-80% of the total weight of the premix compound, the particle sizes of 70-100% ulipristal acetate and the disintegrating agent are less than or equal to 75 micrometers. The ulipristal acetate dispersible tablet disclosed by the invention can take effect quickly in vivo, can realize more effective emergency contraception effect, and is wider in application range.

The invention relates to an ulipristal acetate medicine composition comprising, by weight, 3-10% of ulipristal acetate micro-particles, 70-90% of a diluting agent, 3-6% of a bionding agent, 4-12% of a disintegrant, and 0-2% of a lubricating agent. The particle size D90 of the micro-particles is no higher than 10mum. The diluting agent is selected from lactose, microcrystalline cellulose, mannitol, and mixtures thereof. The bonding agent is hydroxypropyl methylcellulose. The disintegrant is sodium carboxymethyl starch. The lubricating agent is selected from magnesium stearate, silicon dioxide, talc powder, and mixtures thereof. The composition has excellent dissolution profile, good friability, and good homogeneity.

The invention relates to an ulipristal acetate intermediate product and a preparation method thereof. In particular, the invention discloses multiple intermediate products for preparing 3,3,20,20-bis (ethylene dioxy)-17 alpha-hydroxy-19-norpregna-5(10),9(11)-diene (namely, a compound represented as formula VII), and a preparation method thereof, wherein structures of the intermediate products are represented as formula I, formula II, formula III, formula IV or formula V. Furthermore, the invention discloses a method for preparing the compound represented as formula VII. The method disclosed by the invention is easily available in raw material, mild in reaction condition, high in yield, relatively low in cost, low in byproduct content in reaction process, high in target product purity and applicable to industrial production.

The invention discloses a preparation method of ulipristal acetate and an intermediate thereof, and belongs to the field of pharmaceutical synthesis. The preparation method of the ulipristal acetate comprises the following steps: by taking 3,3-(ethylenedioxy)-19-methylestra-5(10),9(11)-diene-3,17-diketone as raw material, enabling the raw material to react with sodium acetylide or potassium acetylide to obtain a compound III, carrying out high-selectivity epoxidation by oxide to obtain a compound IV, subsequently enabling the compound IV to react with 4-(N,N-dimethyl amino) phenyl magnesium bromide Grignard reagent to obtain a compound V, then enabling the compound V to react with phenyl sulfonic acid chloride to obtain a compound VI, enabling the compound VI to respectively react with sodium methoxide and trimethyl phosphate to obtain a compound VII, hydrolyzing and removing a protection group to obtain a compound VIII, finally carrying out acetylation reaction to obtain the ulipristal acetate, wherein the reaction formulae are as shown in the description. The method is short in synthetic route, mild in reaction conditions, high in yield and purity of products, low in cost, stable and controllable in quality, and is suitable for industrial production.

The invention discloses solid dispersion of ulipristal acetate which is prepared from 1 part by weight of ulipristal acetate and 3-20 parts by weight of auxiliary material, wherein the auxiliary material is one or combination of more than two selected from lactose, mannitol, sorbitol and povidone. The invention also discloses a solid preparation of the ulipristal acetate which is prepared from the solid dispersion of the ulipristal acetate and the conventional preparation auxiliary material, wherein the conventional preparation auxiliary material comprises filler, a disintegrating agent, a binding agent, a lubricating agent or flow aid. The solid preparation of the ulipristal acetate disclosed by the invention has higher dissolution rate compared with the ulipristal acetate tablet disclosed by the Chinese patent with the publication number of CN102245173A, the dissolution rate of the ullipristal acetate in a slightly soluble medium can be greatly increased, further bioavailability of the ulipristal acetate is improved and a pharmaceutical effect is guaranteed.

The invention discloses a polycrystalline type A1 and a polycrystalline type A2 of ulipristal acetate (shown as a formula I) not containing any solvate, and preparation methods, a medicinal composition and medicinal application thereof. As proved by smelting point, X-ray powder diffraction (XRD), infrared spectrogram (IR), differential thermal analysis spectrogram (DSC) and thermal weight loss spectrogram (TG), the polycrystalline type A1 and the polycrystalline type A2 of ulipristal acetate prepared by using the methods are extremely stable under the conditions of temperature, illumination and moisture, and contribute to long-time storage. A used crystallization solvent is safe and is easy to remove, the prepared polycrystalline type A1 and polycrystalline type A2 can be directly applied to preparation processing, and the preparation methods are easy to operate, and suitable for industrial production.

The invention provides a novel method for synthesizing a progesterone receptor regulator, ulipristal acetate of formula I. According to the invention, the method has the advantages of ingenious conception, high yield and high purity, the cost is greatly reduced, and the method is suitable for industrial production.

The invention discloses ulipristal acetate related chiral impurities and a synthetic preparation method thereof. Part of chiral impurities can be prepared by the following steps: by taking 3-ketal asan initial raw material, carrying out an addition reaction to obtain an intermediate II; deprotecting the intermediate II in an acidic condition to obtain an intermediate III; carrying out hydrolysisand oxidation to obtain an intermediate IV; and adding protecting groups to obtain the part of chiral impurities; or carrying out a Grignard reaction on a 3,20-diketal oxidative product to obtain thepart of chiral impurities. Structures of all the impurity compounds are confirmed by a magnetic resonance hydrogen spectrum, a high resolution mass spectrum and high performance liquid chromatography.The purities of the ulipristal acetate related chiral impurity compounds prepared by the method are over 95% and can be used as reference substances for quality research.

The invention discloses a novel preparation method of ulipristal acetate key intermediate 3,3,20,20-double (ethylenedioxy group)-5 alpha, 17 alpha- dihydroxyl-11 bata-[4-(N,N- dimethyl amidogen)- phenyl]-19-norprogesterone-9(11)-alkene, namely 3,3- ethylenedioxy group-17 beta-cyangroup female steroid-5(10), 9(11) diene-17 alpha-alcohol is used as a raw material, through the protection of hydroxyl, the addition of Grignard reagent and cyangroup, and the protection of ketal, and the target compound is obtained finally through 1,4 addition of alpha, beta unsaturation epoxide under the catalysis of a system of cuprous halides and dimethyl sulfide. The raw materials used in the method are safe and reliable, reaction is easy to control, reaction yield and stereoselectivity are high, and the method is applicable for industrial production.

The invention discloses a preparation method of a key intermediate of Ulipristal acetate. The key intermediate of the Ulipristal acetate has a structure of a formula II. A compound IV is prepared through Wittig reaction by using a compound III, a compound V is prepared through selective oxidization, and finally secondary alcohol at a No.20 site is oxidized into carbonyl by using oxidant to obtain the key intermediate of the Ulipristal acetate. The synthesis route and the synthesis steps of the key intermediate of the Ulipristal acetate are simple and convenient, and the operation is easy to conduct; the obtained product has the advantages of low cost, high yield and high purity; and the preparation method is suitable for industrial production.

The invention provides a preparation method of a ulipristal acetate key intermediate 3,3,20,20-bis(ethylenedioxy)-17alpha-hydroxy-5,10-epoxy-19-norpregn-9(11)ene. The preparation method comprises the following steps: dissolving 3,3,20,20-bis(ethylenedioxy)-17alpha-hydroxy-19-norpregn-5(10),9(11)diene in dichloromethane, carrying out treatment in an ice bath under pyridine conditions, adding anhydrous magnesium sulfate, hexachloroacetone and 30% oxydol, and stirring in the ice bath to react for 1.5 hours, thereby obtaining 3,3,20,20-bis(ethylenedioxy)-17alpha-hydroxy-5,10-epoxy-19-norpregn-9(11)ene; and mixing the 3,3,20,20-bis(ethylenedioxy)-17alpha-hydroxy-5,10-epoxy-19-norpregn-9(11)ene, sodium-thiosulfate-pentahydrate-containing ice water and dichloromethane to react, and carrying out skimming, extraction, washing, drying, filtration and drying by distillation to obtain the 3,3,20,20-bis(ethylenedioxy)-17alpha-hydroxy-5,10-epoxy-19-norpregn-9(11)ene. The concentration of the oxydol used in the preparation method is 30%, so the potential safety hazard is low.