43 results about "Bazedoxifene" patented technology

The present invention relates to solid dosage formulations containing conjugated estrogens and bazedoxifene, or a salt thereof. In some embodiments, the compositions include a core comprising conjugated estrogens, and at least one coating that comprises bazedoxifene, or a salt thereof.

The invention discloses a new synthetic method of bazedoxifene. Bazedoxifene is prepared by the steps of bromination, substitution, reductive amination, substitution, cyclization, deprotection, and the like of azepane which is selected as a raw material. The synthetic method of the invention has the advantages of mild reaction conditions, simple and convenient operating process, easily obtained reagent, and low cost.

A combination product containing at least two active compounds, O-desmethylvenlafaxine or a pharmaceutically acceptable salt thereof and bazedoxifene or a pharmaceutically acceptable salt thereof is described. Also described are methods of making and using this combination product to treat a variety of conditions associated with low circulating estrogen levels or low estrogen receptor activity.

The invention discloses a preparation method of bazedoxifene. The preparation method of the bazedoxifene comprises the following steps: taking 1-(4-Pg1oxy-phenyl)-allylene (II) and N-[4-(2-azacycloheptane-1-yl- ethyoxyl-benzyl)]-N-[4-(Pg2 oxyphenyl)] hydrazine (III) to perform addition cyclization reaction and acquire 1-[4-(2-azacycloheptane-1-yl- ethyoxyl-benzyl)]-2-(4-Pg1oxy-phenyl)-3-methyl-5-(Pg2oxy)-1H-benzpyrole (IV); performing deprotection on an intermediate (IV) to prepare bazedoxifene (I). The preparation method is simple in process, high in yield, economical and environmental-friendly, so that a novel preparation method for industrial production of the bazedoxifene.

The invention discloses a bazedoxifene intermediate, namely 2-[4-(Pg1 oxyl) phenyl]-3-methyl-5-(Pg2 oxyl)-1-acetyl-indol (I) and a preparation method thereof. The preparation method of the bazedoxifene intermediate comprises the step that 1-(4-Pg1 oxyl-phenyl)-allylene (II) and N-[4-(Pg2 oxyl) phenyl] acetamide (III) are subjected to oxidation ring-closure reaction so as to obtain the bazedoxifene intermediate, namely the 2-[4-(Pg1 oxyl) phenyl]-3-methyl-5-(Pg1 oxyl)-1-acetyl-indol (I) through one step. The intermediate is stable in natural. The preparation method is concise, economical and environment-friendly and can be used for providing a new effective intermediate for industrial production of bazedoxifene bulk drugs.

The invention relates to a method for preparing an impurity A having the purity of more than 97% from a bazedoxifene raw material, can be applied in research of reference substances and belongs to the field of medicine.

The invention discloses a preparation method of bazedoxifene acetate polycrystalline type B. Bazedoxifene free alkali and glacial acetic acid are taken as raw materials and salified to obtain the bazedoxifene acetate polycrystalline type B. The operation conditions of the preparation process are simple and do not need to be carried out under the protection of inert gas; no antioxidant is used in the preparation process; the yield and purity of the prepared product are high, and therefore the product is suitable for industrial production.

The invention deals with new crystalline salts of bazedoxifene, by means of which a high API quality can be achieved in a high yield.

The present invention is related to a process for the preparation of 5-benzyloxy-2-(4-benzyloxyphenyl)-3-methyl-1H-Indole (formula-1, a useful intermediate for the synthesis of bazedoxifene) using 4-benzyloxy propiophenone and 4-benzyloxy phenyl hydrazine hydrochloride.

The invention discloses a preparation method of bazedoxifene. The preparation method comprises the following steps: (a) taking 1-(4-(2-(azepane-1-yl)ethoxy)benzyl)-5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-3-methyl-1H-indole, adding a polar organic solvent, an aprotic lewis acid organic solution and a hydrogen ion provider, and stirring at 0-40 DEG C to obtain a reaction liquid; and (b) separating and purifying the reaction liquid obtained in the step (a) to obtain bazedoxifene. In the method disclosed by the invention, the low-cost and easily available aprotic lewis acid such as boron trifluoride is adopted as a catalyst for preparing bazedoxifene, the reaction conditions are mild, the operation is convenient, the safety is high, and the energy consumption is low; the obtained bazedoxifene has high yield and high purity, and the preparation difficulty and production cost of bazedoxifene are lowered; and the method brings a remarkable positive effect and is very suitable for industrialized use.

The invention discloses a bazedoxifene (Viviant) acetate composition and a bazedoxifene acetate film-coated tablet preparation method, and relates to the technical field of medicines. The bazedoxifene acetate composition comprises the following components by weight of 20-26 parts of bazedoxifene acetate, 250-350 parts of a filling agent, 30-50 parts of an adhesive, 8-15 parts of a disintegrating agent, 3-6 parts of an antioxidant, 2-6 parts of a flow aid, 0.1-0.5 part of a lubricant, 1-3 parts of a wetting agent, and a proper amount of a purified water solvent, wherein bazedoxifene acetate is a BCS II type medicine, and the particle size D90 is 30 microns; the antioxidant is vitamin C; and the filling agent is composed of lactose and microcrystalline cellulose, and the ratio of the lactose to the microcrystalline cellulose is 1: 2-2: 1 according to the weight fraction. The fluidized bed granulation technology adopting the process for preparation is simple in process, lower in cost and easy for industrial production.

The invention discloses a preparation method of a pure acetic acid bazedoxifene crystal form A. The preparation method comprises the following process steps of firstly, under the condition of using palladium carbon as a catalyst, dissolving raw materials into a good organic solvent, and introducing hydrogen to react to a non-raw material point; after reaction is completed, filtering to remove the palladium carbon, cooling filtrate, adding acetic acid and a poor organic solvent, stirring, crystallizing, filtering, and drying, so as to obtain a crude product of the crystal form A. The preparation method has the advantages that the technology is simple, the production efficiency is high, and the preparation cost of the pure acetic acid bazedoxifene crystal form A is effectively reduced.

The invention provides a preparation method of 1-(2-haloethyl)azacycloheptane base ligand and its acid salt. The preparation method is suitable for industrial production. The preparation method is characterized in that 1,6-hexanediol as an initial raw material undergoes three-step reactions to produce the 1-(2-haloethyl)azacycloheptane base ligand and its acid salt. The 1-(2-haloethyl)azacycloheptane base ligand and its acid salt are key intermediates for bazedoxifene synthesis. The preparation method has the advantages of cheap raw material, operation simpleness, mild conditions, simple after-treatment and high yield and is a preparation route suitable for industrialization.

The invention belongs to the technical field of medicines, and particularly relates to a preparation method of bazedoxifene oxide, wherein the preparation method comprises the steps: by using bazedoxifene free alkali as a raw material, dissolving in a first benign solvent, adding an organic alkali, and adding a silane protecting group to protect two phenolic hydroxyl groups, and thus obtaining anintermediate 1; dissolving the intermediate 1 in a second benign solvent, and adding an oxidant for oxidation to obtain an intermediate 2; and dissolving the intermediate 2 in a third benign solvent,and adding a protecting group removing reagent to remove two molecular silane protecting groups, and thus obtaining the bazedoxifene oxide. According to the preparation method of the bazedoxifene oxide provided by the invention, a preparation method of 1-[4-[2-(azacycloheptan-1-yl)ethoxy]benzyl]-2-(4-hydroxyphenyl)-3-methyl-1H-indole-5-phenol-N-oxide is provided, and the preparation method has important significance in effectively controlling the quality of bazedoxifene.

Methods are disclosed for treating and/or preventing retinal degeneration is a subject. In some embodiments, the method includes administering to the subject a therapeutically effective amount of a selective estrogen receptor modulator (SERM) to treat the retinal degeneration in the subject. In other embodiments, the SERM is administered orally. In some examples, the SERM is tamoxifen, afimoxifene, raloxifene, bazedoxifene, arzoxifene, desmethylarzoxifene, or a salt or derivative thereof, or combinations thereof.

Methods for treating Shiga toxicosis, caused by infection with Shiga toxin bacteria, are provided. The methods include administering to a subject in need thereof an effective amount of one or more active agents selected from tamoxifen, 4-hydroxytamoxifen, endoxifen, toremifene, raloxifene, bazedoxifene, and pharmaceutically acceptable salts thereof. In some embodiments, the methods further include the administration of an antibiotic or a manganese compound to the subject. Pharmaceutical compositions for the treatment of Shiga toxicosis are also described.

The invention discloses a synthesis method of a bazedoxifene derivative. According to the preparing method of the bazedoxifene derivative, p-anisidine is adopted as a raw material, and through a six-step reaction, the synthesis of the bazedoxifene derivative is achieved. The preparing method of the bazedoxifene derivative is reasonable in technological design and high in operability, the reaction condition is mild, the yield is high, and thus industrialized production can be achieved. The prepared bazedoxifene derivativ bazedoxifene provides an important basis for scientific evaluation of quality, safety and efficiency of bazedoxifene; meanwhile, the bazedoxifene derivative is good in pharmacological activity, can be developed into medicines used for treating osteoporosis, and thus the bazedoxifene derivative has important application value.

The invention discloses a preparation method of bazedoxifene. The preparation method comprises the following steps: (1) reaction materials are mixed, and the reaction materials comprise a bazedoxifeneintermediate of formula I; (2) fixed bed catalytic reaction; (3) post-treatment. The preparation method has the advantages of realization of continuous reaction, fast reaction speed, repeated and continuous use of the catalyst and hydrogen, high reaction safety, no discharge of waste water and waste gas, environmental protection, saving, and easy realization of automation.

The invention provides a preparation method suitable for industrial production of (4-(2-azacycloheptane-1-yl)ethoxy)phenyl)methanol. The method is characterized in that a bazedoxifene synthesis key intermediate (4-(2-azacycloheptane-1-yl)ethoxy)phenyl)methanol is obtained through a three step reaction of low-toxicity 2-(azacycloheptane)-1-ethanol as an initial raw material. The method has the advantages of low-toxicity cheap raw material, simple operation, mild condition, simple post-treatment and high yield, and is a preparation route very suitable for industrialization.