61 results about "TEBIPENEM PIVOXIL" patented technology

The invention discloses a tebipenem pivoxil oral solid preparation and a preparation method thereof. The oral solid preparation disclosed by the invention comprises particles, an isolation coating layer, a taste masking coating layer and a coloring tender taste coating layer, wherein the particles are prepared from tebipenem pivoxil, microcrystalline cellulose and binders. According to the invention, the preparation can be used for overcoming the problem that a part of water in main medicines and excipients has an interaction to affect the quality of a finished product, and is suitably prepared into a medicine.

The invention provides stable tebipenem pivoxil granule composition. The composition comprises tebipenem pivoxil raw material and pharmaceutical excipients, wherein the pharmaceutical excipients comprise a filler, an adhesive and a coating solution; the coating solution comprises an insulation layer, a taste mask layer and a coloring and taste modifying layer; the filler comprises sucrose and microcrystalline cellulose, the amount of the sucrose accounts for 50%-70% of the total weight of the granule composition, and the amount of the microcrystalline cellulose accounts for 5%-15% of the total weight of the granule composition. The invention further provides a preparation method of the composition and an application of the composition in preparation of drugs with an antibacterial function.

The invention relates to a tebipenem pivoxil-containing oral preparation and a preparation method of the tebipenem pivoxil-containing oral preparation. The preparation provided by the invention consists of tebipenem pivoxil and a pharmaceutic adjuvant as the active components. The pharmaceutic adjuvant contains beta-cyclodextrin. The tebipenem pivoxil oral preparation provided by the invention overcomes the defects that the grit feeling is produced when the tebipenem pivoxil oral preparation is taken, the patient compliance is poor and the preparation technology is complicate in the prior art, so that the tebipenem pivoxil oral preparation is an excellent preparation with good taste, high dissolvability, good stability and simple preparation technology.

An oral preparation containing tebipenem pivoxil is characterized by comprising the following components in percentage by weight: 1 to 20 percent of tebipenem pivoxil, 60 to 98 percent of filler, 0.5 to 10 percent of adhesive and 3 to 50 percent of coating agent; and only water is taken as a solvent in the preparation of the oral preparation. The bitter taste of raw medicines is covered by using a taste-covering technology, and the oral preparation is suitable for children. In a whole preparation process, only water is taken as the solvent, so that stability and safety of the preparation in preparation and storage processes are guaranteed.

The invention relates to a preparation method of tebipenem pivoxil and analogue thereof. In the method, carbapenem compound salt with a formula II is used as a raw material to obtain carbapenem compound ester with a formula I under the action of alkali, wherein the carbapenem compound salt with the formula II is prepared by direct reaction of a carbapenem compound with a formula III and ester with a formula IV. According to the invention, high-yield and high-purity salt of tebipenem pivoxil and analogue thereof can be prepared, so that high-yield and high-purity tebipenem pivoxil or analogue thereof can be obtained without column chromatography. Thus, the method provided by the invention is more suitable for industrial production in a large scale.

The invention relates to the field of chemical synthesis, and discloses a preparation method of tebipenem pivoxil. The preparation method comprises the following steps of: performing condensation reaction on azabicyclo phosphate and 3-mercapto-1-(1,3-thiazoline-2-yl) azetidine hydrochloride by taking acetonitrile as a solvent in the presence of diisopropylethylamine; in a mixed solvent consisting of acetic ether and a potassium bicarbonate aqueous solution, performing hydrogenization on the compound shown by formula I to remove p-nitrobenzyl to obtain tebipenem; and under the catalysis of a phase transfer catalyst, adding anhydrous potassium carbonate into the tebipenem and iodomethyl pivalate to perform condensation reaction to obtain the tebipenem pivoxil. By adopting the preparation method, according to the defects of related solvents and operations of purification and the like in the conventional method for preparing the tebipenem pivoxil, co-adapted solvents and purification operations are selected during preparation according to a reaction mechanism, so that the yield of the tebipenem pivoxil is improved, and the preparation method is suitable for industrial production. The formula I is shown in the description.

The invention discloses a preparation method for an intermediate of tebipenem pivoxil shown as formula 1. The preparation method comprises the following step of performing the following reaction on a compound MAP and a compound IV in an organic solvent and water, with the action of (R1)3P and an organic base, under inert gas protection, wherein the volume ratio of the organic solvent and water is 1000 : 1-10 : 1; a reaction temperature is -40-50 DEG C; and R1 represents phenyl or C2-C8 alkyls. The preparation method is easy to operate, simple in post-treatment, with the product having high yield and high purity, and is suitable for industrialized production.

The invention relates to a preparation method of fine tebipenem pivoxil granules. Each fine tebipenem pivoxil granule comprises four parts as follows: a core granule, an isolation coat, a taste masking coat and a coloring and corrigent layer, wherein the core granule is prepared with a high shear mixed granulator, the isolation coat and the taste masking coat are prepared with a fluidized bed cutting and spraying technology, after the coloring and corrigent layer, a taste masking granule, a corrigent, a colorant and flavor are added, the granule is prepared with the high shear mixed granulator; the obtained granules are uniform in size, drug dissolution can be guaranteed, drug stability is improved, further, bad smell of the drug can be masked, and the granules are suitable for children; the adopted preparation process is simple, continuous proceeding of the process can be guaranteed, and the method can be applied to mass production.

The invention belongs to the technical field of pharmaceutical preparations and discloses a pharmaceutical preparation of a tebipenem pivoxil composition and a preparation method of the pharmaceutical preparation. The pharmaceutical preparation of the tebipenem pivoxil composition comprises the following components in parts by weight: 10-100 parts of tebipenem pivoxil, 10-100 parts of a resin material, 200-1000 parts of a substrate material, 200-1000 parts of a filler, 1-10 parts of a defoamer, 1-10 parts of a surfactant, 10-100 parts of a lubricant and 20-100 parts of a binder. The pharmaceutical preparation of the tebipenem pivoxil composition has good dissolution rate and stability and also covers the bad taste of tebipenem pivoxil, and has a good taste. The preparation method provided by the invention further improve the dissolution rate of medicines, and the bitterness caused by tebipenem pivoxil is effectively covered, the effectiveness and safety of the preparation are guaranteed and the medicament compliance of the patient is improved.

The invention relates to a tebipenem pivoxil granule and a preparation method thereof. The granule is prepared according to the following steps: uniformly mixing tebipenem pivoxil, microcrystalline cellulose, lactose and carboxymethyl starch sodium, adding water to prepare a soft material, putting in a ball rolling machine for extruding and preparing pills, and drying by using a fluidized bed, and dressing. The dressing layer comprises a resin layer and a powder coating. The preparation method is capable of guaranteeing medicine stability through a special dressing prescription under the prerequisite of keeping the dissolution effect, and also is capable of masking the bitterness of the granule and improving the mouthfeel. The preparation method is simple in operation, short in man hour, high in yield and suitable for industrialized production.

The invention provides a preparation method of tebipenem pivoxil, and relates to the technical field of pesticide synthesis. The preparation method of the tebipenem pivoxil comprises the following steps that 1-(4,5-dihydro-2-thiazolyl) azetidine-3-thiol hydrochloride and 1 beta-methyl vinyl phosphate are used as raw materials to take a reaction under the existence of diisopropylethylamine, and an acetonitrile water solution is used for washing to obtain an intermediate I; the intermediate I, an n-butyl alcohol water solution, a palladium-carbon catalyst and sodium bicarbonate take a mixed reaction, and treatment is performed to obtain an intermediate II; the intermediate II and chloromethyl pivalate take a reaction through phase transfer catalyst catalysis under the existence of diisopropylethylamine and dimethylformamide to obtain an intermediate III; the intermediate III and a sodium bicarbonate water solution are mixed, ethyl acetate is added, and reaction and refining are performed to prepare the tebipenem pivoxil. The preparation method has the advantages that the purity and the yield of the intermediates are obviously improved; the purity of the final product of the tebipenem pivoxil reaches 99.21 to 99.78 percent; the yield reaches 88.7 to 92.1 percent.

The invention provides a tipipenem pectin granule and a preparation method thereof, and relates to the technical field of medicine and its preparation. A tipipenem granule, comprising the following raw materials in parts by weight: 600 to 700 parts of tipipenem, 3500 to 4500 parts of diluent, 40 to 50 parts of hydroxypropyl cellulose, and 455 to 470 parts of coating agent I 380-400 parts of coating agent II, the coating agent I is composed of ethyl cellulose suspension and talcum powder at a weight ratio of 10-20:1, the coating agent II is composed of gastric-soluble acrylic resin, Talc powder, hydroxypropyl methylcellulose and aspartame are composed in a weight ratio of 25-40:1-3:1:1.5-2.5. The tipipenem ester granule of the present invention uses tipipenem ester as the main drug, strictly screens and controls the ingredients of the excipients, optimizes the proportion, has stable drug efficacy under high temperature and high humidity environment, safe quality, high dissolution rate and excellent process. Easy to control and suitable for industrial production.

The invention discloses a refining method of a side chain of tebipenem pivoxil. The refining method comprises the following steps: oxidizing a coarse side chain of tebipenem pivoxil into a disulphide; purifying the disulphide; and then reducing the disulphide into the side chain of tebipenem pivoxil to prepare a refined product of the side chain of tebipenem pivoxil. Compared with a method of physically refining the coarse side chain of tebipenem pivoxil, the refined side chain of tebipenem pivoxil prepared by the refining method is high in yield, high in purity and stable in chemical property, and the refining method disclosed by the invention has the advantages of being simple to operate, economical and practical, suitable for industrial production and the like.

The invention discloses a novel synthetic method of a tebipenem pivoxil side chain. The method employs cheap and easily available raw material, has simple experimental operations, high overall yield and is applicable to industrialized production.

The invention relates to the technical field of medicines and particularly relates to a method for preparing Tebipenem pivoxil. The method for preparing the Tebipenem pivoxil, provided by the invention, at least comprises the following steps: (1) condensation reaction; (2) hydrogenation reaction; (3) esterification reaction; and (4) purification and refining.

The invention discloses a preparation method of an antibacterial medicament tebipenem pivoxil. (4R,5R,6S)-3-((diphenyl-phosphoroso-carbonyl)oxyl)-6-((R)-1-ethoxyl)-4-methyl-7-carbonyl-1-azabicyclo[3.2.0]heptane-2-alkenyl-2-carboxylic acid p-nitro ester(6-MAP(I)) serving as a raw material reacts with 1-(4,5-dihydro-2-thiazolinyl)-3-sulfydryl azetidine hydrochloride (II) in the presence of alkali to obtain (4R,5S,6S)-3-((1-(4,5-dihydro-2-thiazolinyl)-3-azetidine) sulfenyl)-6-((R)-1-ethoxy)-4-methyl-7-oxygen-1-azabicyclo[3.2.0]heptane-2-alkenyl-2-carboxylic acid p-nitro ester (III); the protecting group of the compound (III) is removed under the catalytic hydrogenation condition to obtain (4R,5S,6S)-3-((1-(4,50dihydro-2-thiazolinyl)-3-azetidine)sulfenyl)-6-((R)-1-ethoxy)-4-methyl-7-oxygen-1-azabicyclo[3.2.0]heptane-2-alkenyl-2-carboxylic acid (IV); and the compound (IV) reacts with chloromethyl pivalate and sodium iodide or potassium iodide in the presence of alkali to obtain tebipenem pivoxil (V). According to the preparation method, the selected initial raw materials are low in price and easily available, so that the synthesizing route is simplified, the raw material utilization and total yield can be improved; and the intermediate substance obtained in the reaction is purified by using a re-crystallization method with high yield, less three wastes are generated in the reacting process, and the low cost is advantageous to industrial production.

The invention relates to a crystal of an intermediate of carbapenem antibiotic tebipenem pivoxil and a preparation method thereof. The crystal type of the intermediate comprises a type A crystal of the intermediate of tebipenem pivoxil and a type B crystal of the intermediate of tebipenem pivoxil, wherein in a powder X-ray diffraction pattern, the type A crystal has main peaks when the diffraction angle 2(theta) is 5.90, 8.02, 14.93, 19.30, 22.65, 22.10, 24.16, 26.50 and 26.98; the type B crystal has main peaks when the diffraction angle 2(theta) is 6.76, 8.25, 15.13, 16.35, 17.47, 21.02, 22.31, 31.31 and 32.77. The preparation method of the crystal form mainly comprises a preparation method of the type A crystal of the intermediate and a method for preparing the type B crystal through crystal transformation of the type A crystal.

The invention discloses a preparation method for tebipenem pivoxil shown as formula 1. The preparation method comprises the following step of performing the following reaction on a compound III and a compound IV in an organic solvent and water, with the action of (R1)3P and an organic base, under inert gas protection, wherein the volume ratio of the organic solvent and water is 1000 : 1-20 : 1; a reaction temperature is -40-50 DEG C; and R1 represents phenyl or C2-C8 alkyls. The preparation method is easy to operate, simple in post-treatment, with the product having high yield and high purity, and is suitable for industrialized production.