53 results about "Fosaprepitant dimeglumine" patented technology

The invention provides a sterile lyophilized preparation containing fosaprepitant, and a preparation method thereof. According to the invention, an effective dosage of fosaprepitant dimeglumine is adopted as an effective component, and auxiliary materials such as a solubilizer, a complexing agent, a lyophilization excipient, and an acidity adjusting agent are contained in the preparation. The lyophilization excipient does not comprise lactose, and is selected from one or a combination of mannitol, glucose, dextran, sorbitol, arginine, and glycine. The components are dissolved in injection water. The solution is sterilized, filtered, sub-packaged, and lyophilized. The prepared sterile lyophilized preparation has excellent high-temperature stability, illumination stability, and accelerated-experiment stability. When in use, the sterile lyophilized preparation provided by the invention is added into a solvent, so that an injection solution with an appropriate concentration is prepared and can be used. The preparation has good treatment effect upon chemotherapy-induced nausea and vomiting. With the form of injection medication, patient compliance is improved. The preparation process of the lyophilized preparation is simple. The lyophilized preparation is suitable for industrialized productions.

The invention provides a preparation method of fosaprepitant dimeglumine. The preparation method comprises the following steps: by taking aprepitant as a raw material, carrying out phosphorylation on the raw material under an alkaline condition to obtain a dibenzyl ester intermediate; further hydrolyzing the intermediate to obtain fosaprepitant; and further reacting with N-methyl-D-glucosamine to obtain the fosaprepitant dimeglumine. The method provided by the invention is simple to operate and mild in reaction condition, and avoids pressurization and v, so that the method is safe and effective and suitable for industrial production on a large scale.

A fosaprepitant dimeglumine freeze-dried preparation prepared by adopting the invention has the characteristics of porosity, stable quality, high redissolution speed, good clarity and the like. The invention provides a preparation method of a fosaprepitant dimeglumine freeze-dried preparation for injection, which comprises the following steps: (A) pre-freezing: firstly, cooling a fosaprepitant dimeglumine injection to (-12)-(-14) DEG C, and freezing through temperature oscillation; and then, cooling to (-32)-(-35) DEG C, and oscillating and freezing for 42-62 minutes; (B) sublimating: vacuumizing in a box body until the air pressure is 12-17 Pa, heating a product to (-35)-(-37) DEG C, and preserving the temperature for 8-10 hours; and intermittently injecting nitrogen gas, oscillating for 1-1.5 hours by taking air pressure (17-22 Pa) in the box body as an amplitude, heating the product to (-25)-(-29) DEG C, and preserving the temperature for 15-18 hours; and (C) drying: gradually heating the medicament to 38-42 DEG C, and preserving the temperature for 1-2 hours.

The invention provides a preparation method of fosaprepitant dimeglumine. The preparation method is characterized in that aprepitant is used as a raw material, under an alkaline condition, dibenzyl ester intermediate compound is obtained by phosphonylation, the intermediate compound is further hydrogenated and catalyzed to obtain fosaprepitant, the fosaprepitant is further reacted with N-methyl-D-glucamine, and finally the fosaprepitant dimeglumine is obtained. The preparation method has the advantages of short reaction cycle, simpleness in operation, low production cost and good product quality; the purity of the finished product is more than 99.5 percent, and the content of single impurity is less than 0.1 percent; and the preparation method is suitable for large-scale industrial production.

The invention relates to the field of medicament preparation, and particularly relates to a fosaprepitant dimeglumine injection composition and a preparation method thereof. The pharmaceutical active ingredients of the fosaprepitant dimeglumine injection composition include the following components in parts by weight: 180-250 parts of fosaprepitant dimeglumine, 12.0-20.0 parts of disodium edetate, 50.0-80.0 parts of polysorbate-80, 250-400 parts of lactose and 2000-3000 parts of water for injection. The preparation method comprises the following steps: dissolving, preparing, adsorbing, pre-freezing, performing sublimation drying and mounting an injection piston. The fosaprepitant dimeglumine injection composition provided by the invention is prepared from the low low-cost auxiliary materials according to a self-developed formula, has the same medicament effect in comparison with the existing fosaprepitant medicament available in America, is low in medicament cost and has no side effect basically; and the lactose used as excipient resists infection and is easy to absorb, so that favorable pharmaceutical effect can be achieved, and crushing of the medicament during storage can be avoided.

The invention provides a sterile lyophilized compound preparation containing fosaprepitant and palonosetron hydrochloride, and a preparation method thereof. According to the invention, effective dosages of fosaprepitant dimeglumine and palonosetron hydrochloride are adopted as effective components, and auxiliary materials such as a solubilizer, a complexing agent, an excipient, and an acidity adjusting agent are contained in the preparation. The preparation is filtered, sterilized, sub-packaged, and lyophilized. When in use, the sterile lyophilized compound preparation provided by the invention is added into a solvent, such that injection solution with an appropriate concentration is prepared and can be used. With one time of medication, clinical demands of two treatment medicines can be satisfied, such that patient compliance is improved. The preparation method of the compound preparation is simple, and the method is suitable for industrialized productions.

Solid compositions having about 150 mg to about 245 mg Fosaprepitant that are stable after storage at about 25° C. for 6 months and processes for preparing solid Fosaprepitant compositions that are stable after long term storage at room temperature. The processes include freezing a Fosaprepitant solution in the primary packaging container at a first freezing temperature; applying vacuum at second temperature that is higher than the freezing temperature; fully stoppering the primary packaging container; and sealing the stoppered primary packaging container.

The invention provides an application of a borane-pyridine complex in preparation of an NK-1 receptor antagonist fosaprepitant dimeglumine. The application is characterized by comprising the followingsteps: step 1) catalyzing aprepitant dibenzyl phosphate under the action of the borane pyridine complex to prepare fosaprepitant; and 2) reacting fosaprepitant with N-methyl-D-glucosamine to generatefosaprepitant dimeglumine. The borane-pyridine complex is used as the catalyst, aprepitant dibenzyl phosphate can directly generate fosaprepitant, then the fosaprepitant dibenzyl phosphate reacts with N-methyl-D-glucosamine to generate fosaprepitant dimeglumine, the reaction is mild, and conversion of raw materials can be completed quickly at the temperature of about room temperature only by using a small amount of catalyst. The catalytic efficiency is high, the reaction conditions are mild and the yield is high. The high-purity and high-yield fosaprepitant can be obtained by recrystallizingthe reaction crude product with deionized water, the post-treatment is extremely simple, and the fosaprepitant dimeglumine is generated by reacting the reaction crude product with N-methyl-D-glucosamine so that the purity and the yield are high.

The invention relates to the field of medicaments, and in particular provides a synthesis method of fosaprepitant dimeglumine. According to the method of the invention, aprepitant is employed as initial material to be reacted with tetrabenzyl pyrophosphate in anhydrous tetrahydrofuran with sodium hexamethyldisilazide as a base to obtain dibenzyl ester intermediate, a benzyl group of the dibenzyl ester is removed in anhydrous methanol to generate single-benzyl ester intermediate, which is hydrogenated to remove a remaining benzyl group, and salified with meglumine to obtain fosaprepitant dimeglumine. The method comprises three major steps: (1) preparing intermediate S100902; (2) preparing crude fosaprepitant dimeglumine; and (3) refining crude fosaprepitant dimeglumine. The synthesis method is featured as abundant available raw materials, moderate and controllable reaction conditions, simple process, high yield and is suitable for industrial production.

The present invention relates to a fosaprepitant dimeglumine freeze-dried powder injection and a preparation method thereof, wherein the fosaprepitant dimeglumine freeze-dried powder injection comprises an active component fosaprepitant dimeglumine and a stabilizer so as to avoid the use of Tween 80 and lactose and improve the product safety. According to the present invention, during the preparation process, the solubility of fosaprepitant dimeglumine is increased by using the tert butyl alcohol-water cosolvent, such that the concentration required by the preparation is achieved so as to meet the production requirement; and the generation of foams is avoided during the preparation process, such that the sterilization and filtration rate and the filling accuracy are improved.

The invention belongs to the technical field of medicine chemistry, and particularly relates to a novel preparation method of fosaprepitant dimeglumine. According to the preparation method, triethyl silane is used for replacing hydrogen, and high-pressure equipment can be prevented from being used, so that the safety is improved, and the obtained product is good in appearance, high in purity and suitable for industrial mass production.

The present application provides a stable, ready-to-use fosaprepitant dimeglumine formulation which is easy to administer without need of any reconstitution step and has a desirable solubility, stability and safety profile. The concentration of the fosaprepitant dimeglumine in the liquid formulation is preferably less than about 80 mg/ml, or more preferably between about 20 mg/ml to about 60 mg/ml. In certain embodiments, the liquid formulation retains at least about 90% chemical stability of the fosaprepitant dimeglumine after storage for a commercially reasonable amount of time at a temperature between about 0° C. to about 40° C.

The invention relates to a fosaprepitant dimeglumine composition for injection and a preparation method thereof, the pharmaceutical composition is composed of fosaprepitant dimeglumine, 15-polyethylene glycol hydroxystearate and sodium calcium edentate, prescription is simple, technology is simple, and the prepared product has the advantages of stable quality, safety and reliability.

The invention discloses detection methods of a fosaprepitant dimeglumine raw material or preparation and an impurity in fosaprepitant dimeglumine raw material or preparation. According to the detection methods, a sample solution of the fosaprepitant dimeglumine raw material or preparation is detected and analyzed by using high efficiency liquid chromatography; an immobile phase of a chromatographic column used for detection is octadecyl silane bonded silica gel; a mobile phase comprises a mobile phase A and a mobile phase B, wherein the mobile phase A contains a phosphate buffer solution; themobile phase B contains acetonitrile; the gradient elution is carried out on the sample solution of the fosaprepitant dimeglumine raw material or preparation within 0 to 50min by the mobile phase A and the mobile phase B. The detection methods are simple and convenient to operate, easy to control and low in detection cost, and can be used for effectively monitoring the impurity in a fosaprepitantdimeglumine drug and accurately measuring the content of the impurity.