106 results about "Dutasteride" patented technology

This invention provides methods of treating a mammalian subject in need of androgen therapy by orally administering to the subject testosterone, a testosterone ester, or a testosterone precursor in an oil vehicle and by administering to the subject a modulator such as finasteride or dutasteride which increases testosterone bioavailability in the subject.

The present invention relates to a process for the preparation of Dutasteride, which is chemically known as 17β-N-[2,5-bis (trifluoromethyl) phenyl] carbamoyl-4-aza-5-α-androst-1-en-3-one and can be represented by Formula (I).

The present invention relates to dutasteride liquid soft capsules and a preparation method thereof. The soft capsules comprise a capsule shell and contents, wherein the contents mainly comprise, by weight, 0.05-0.3% of dutasteride, 19.8-94.8% of medium chain triglyceride, and 5-80% of mono-caprylin glycerate. The soft capsules have characteristics of rapid dissolution, simple preparation process and the like.

A method for treating hair loss caused by androgenic alopecia and/or male pattern baldness. The method, which not only slows hair loss but causes hair re-growth, includes approximately daily application to a subject's scalp of a novel composition comprising finasteride (Propecia® or Proscar®), dutasteride (Avodart®), and minoxidil (Rogaine®) as active ingredients in a hypoallergenic cream-based vehicle, preferably coupled with daily ingestion of 1 mg per day of finasteride (Propecia® or Proscar®), application to the scalp of 5% minoxidil (Rogaine®) foam approximately once per day, and use of a ketoconazole-containing shampoo (e.g., Nizoral®) approximately 2-3 times per week. The method described herein also resolves scalp dermatitis in atopic subjects suffering therefrom. A method for making the novel composition is also provided.

The invention relates to a soft capsule with contents containing dutasteride, a diluent and a surfactant, wherein the diluent is selected from one of a group consisting of soybean oil, peanut oil, corn oil and a medium-chain triglyceride, and the surfactant is selected from one or two of a group consisting of span 80 and span 85. Preferably, the weight percentage content of dutasteride accounts for 0.042%-0.143% of that of the contents, the weight percentage content of the diluent accounts for 79.87%-98.46% of that of the contents, and the weight percentage content of the surfactant accounts for 1.498%-19.99% of that of the contents. The dutasteride-containing soft capsule prepared by the prescription provided by the invention has wide raw material sources, strong stability, good safety, high dissolution rate and good bioavailability.

The invention discloses a novel feeding sequence for preparing dutasteride by taking 3-ketone-4-aza-5alpha-aetioallocholane-1-olefin-17beta-carboxylic acid, pyridine, thionyl chloride and 2,5-(trifluoromethyl)phenylamine as raw materials, as well as concrete operation steps and embodiments. By using the method, the problems of low yield and high cost of the process and operation for synthesizing a crude product of the dutasteride by using the 3-ketone-4-aza-5alpha-aetioallocholane-1-olefin-17beta-carboxylic acid as a raw material at current are solved, the yield of the crude product of the dutasteride synthesized by using the 3-ketone-4-aza-5alpha-aetioallocholane-1-olefin-17beta-carboxylic acid as the raw material is greatly increased, the industrial cost is reduced, and the process is simple, is simple and convenient to operate and is more suitable for the industrial production of the dutasteride.

The invention relates to a preparation method of dutasteride. The method comprises the following steps: preparing acyl chloride from a compound shown in the formula (1), performing an amidation reaction with 2,5-bis(trifluoromethyl)aniline to obtain a compound shown in the formula (2), and performing 1,2-dehydrogenation to obtain dutasteride shown in the formula (3). The preparation method provided by the invention has the following advantages: the reaction conditions are mild, the intermediate of each step can be purified easily, and the quality is stable and controllable; the yield is higher, and the cost is low; and the method is suitable for industrial production. The formula (1) is shown in the description.

The invention belongs to the technical field of medicine, and provides a preparation method of dutasteride. The preparation method comprises the following steps: A) an industrial-grade compound III is washed by acetone after beaten and refined by formic acid, and a refined compound III product is obtained; B) the refined compound III product has a chlorination reaction to generate a compound II; C) the compound II has a condensation reaction with 2,5-bis (trifluoromethyl) phenylamine, a product is cooled and filtered, a filtrate is collected, a hydrochloric acid solution is added for washing, an organic phase is separated, pressure is reduced to evaporate s solvent, and a crude dutasteride product is obtained; and D) the crude dutasteride product is dissolved by an organic solvent and decolorized, an anti-solvent is added for crystallization, and high-purity dutasteride is obtained. Side reactions are reduced, high-purity dutasteride can be obtained through preparation, and the productive cost is reduced.

The invention provides a pharmaceutical composition containing dutasteride used for increasing bioavailability and a preparation method, the pharmaceutical composition containing dutasteride comprises 0.02-0.5% (W/W) of dutasteride, 30-70% (W/W) of oily medium and 25-66% (W/W) of surfactant; wherein the surfactant is one or more selected from span, tween, lecithin, soyabean lecithin or cholesterin. Compared with the prior art, the preparation prepared by the composition can obviously increase the dissolution in vitro of dutasteride, and the bioavailability can reach 144%.

The invention discloses a synthesis technology of dutasteride, comprising the following steps of: using the acidity of DT4 carboxyl to directly react with ammonia to generate DT4-ammonium salt; dehydrating the obtained ammonium salt into DT4-amide, and performing an amino exchange reaction between amide and BTFMA in the presence of a catalyst so as to prepare dutasteride. With DT4 as a starting material, dutasteride is synthesized by three reactions of salt formation, dehydration and amino exchange. During the reactions, thionyl chloride, oxalyl chloride, pivaloyl chloride or methylsulfonyl chloride which is sensitive to the environment is avoided, special expensive catalysts such as DBU, copper powder and the like are not needed, and harmful and poisonous chemical materials are avoided. The product has good product yield and high purity, and is easy to refine. The synthesis technology has advantages of low cost and few ''three wastes'', is easy and simple to operate, conforms to green chemical synthesis requirements, and lays a good industrial foundation for realizing large-scale green clean production of high-yield and high-purity dutasteride.

The invention discloses a compound preparation, and a preparation method thereof. The compound preparation comprises active components of tamsulosin and dutasteride, wherein tamsulosin is enteric pellets, particles or tablets, and dutasteride is soft capsules. tamsulosin and dutasteride are filled in one hard capsule. The invention also discloses the preparation method of the compound preparation.

The invention relates to a self-microemulsion dutasteride orally-taken preparation and a preparation method thereof. The self-microemulsion composition comprises the following components in percent by weight: 0.05%-0.3% of dutasteride, 5%-75% of oil, 20%-60% of an emulsifier and 4%-50% of a co-emulsifier. After being cured, the self-microemulsion auxiliary materials can be prepared into preparations such as tablets or capsules; after being quickly disintegrated in a stomach, the preparation can be form emulsion drops with average grain size of 10 nm-100 nm in a gastrointestinal tract after being self-microemulsified, so that solubility and dissolution rate of the dutasteride can be improved, and absorption of the dutasteride in the gastrointestinal tract can be promoted.

Disclosed herein are topical compositions of 5-α reductase inhibitors, such as dutasteride or finasteride, or a pharmaceutically acceptable salt, ester, or derivative thereof and the use of the compositions for the treatment of hair loss secondary to endocrine therapy in patients with breast cancer (Endocrine Therapy-Induced Alopecia or ETIA), androgenetic alopecia (AGA), alopecia areata, and hirsutism. The topical composition is advantageous over the existing oral compositions of 5-α reductase inhibitors because the topical composition is safer and more effective. The topical formulation may allow for a slow release of the active ingredient dutasteride, better penetration at the therapeutically effective amount of dutasteride with an improved safety profile because it does not need to travel through the bloodstream to be efficacious, thereby minimizing the risk of systemic side effects.

The invention discloses a dutasteride liquid hard capsule which comprises a hard capsule shell and contents, and the contents comprise dutasteride, a diluent and an anti-oxidant. The invention also discloses a preparation method of the dutasteride liquid hard capsule, which comprises the following steps: weighing dutasteride, the diluent and the anti-oxidant according to the weight composition of the contents, dissolving by stirring, well mixing to obtain a mixture which is the contents, filling the mixture into a hard capsule shell, sealing to obtain the dutasteride liquid hard capsule. The dutasteride liquid hard capsule of the invention has the characteristics of high disintegration and dissolution rate, and good stability, and the preparation method has the characteristics of simple operation, low production cost, and controllable quality.

The invention relates to a preparation method of dutasteride intermediate, and specifically relates to a preparation method of 3-carbonyl-4-aza-5[alpha]-androstane-17[beta]-carboxylic acid. According to the preparation method, for hydrogenation, a carboxylic acid derivative is used as a hydrogen donor to perform transfer hydrogenation, so that hydrogen pressure reduction is prevented and expensive catalysts such as PtO2, Pd/C, raneys nickel, zinc powder and the like are not needed; and for purification, a specific alcoholic solvent is used to perform crystallization, so that 5-beta isomer produced by reduction can be separated effectively. The obtained product has high purity, operations are simplified and the method is suitable for industrialized production.

The invention relates to a synthesis method of a dutasteride intermediate, belonging to the field of medicament. The synthesis method comprises the steps of dissolving 3-oxo-4-aza-androst-5-ene-17beta-carboxamide in organic solvent, adjusting pH value, stirring at room temperature, slowly adding reducing agent NaBH3CN, carrying out hydrogenation reaction for 1h, adjusting pH value with 10% NaOH solution, extracting with CH2Cl2, drying, filtering, evaporating filtrate under reduced-pressure to be dry to obtain crude product and recrystallizing the crude product. The synthesis method has the advantages that the ratio of the obtained alpha-isomer is high, the yield is higher, the production cost is simultaneously reduced, and the experiment safety is improved.

The invention discloses a process for preparing dutasteride, and belongs to the field of pharmaceutical chemical synthesis. The process comprises the following steps: carrying out 1,2-position dehydrogenation on a compound shown in a formula (1) so as to obtain a compound shown in a formula (2); and after the compound shown in the formula (2) is prepared into acyl chloride, carrying out amidation on the acyl chloride and 2,5-bis(trifluoromethyl)aniline so as to obtain dutasteride shown in a formula (3). The process disclosed by the invention is simple in operation, mild in reaction conditions, safe and reliable in production, high in reaction yield, low in cost, and suitable for industrial production.

The invention particularly relates to a method for separating and determining degradation impurities in a dutasteride raw material drug and a preparation by virtue of a high performance liquid chromatography. Impurities are generated under a forced degradation condition. According to the method, octadecylsilane bonded silica is taken as a chromatographic column for a filling agent, and linear gradient elution is carried out by virtue of a flow phase A and a flow phase B. Because a dutasteride soft capsule quality standard and any relevant literature or standard are not reported in pharmacopeias of each country, the HPLC is a set of a complete self-established method. By researching the conditions of detection wavelengths, diluent mass concentration and the like, a set of the method suitable for detecting the substance is determined and has the advantages that the detection interference is small, the specificity and the repeatability are good, the accuracy is high, and technical supportis provided for the mass control of a dutasteride soft capsule.