40 results about "Cefditoren" patented technology

The present invention relates to an improved process for the preparation of Cefditoren of formula (I), the said process comprising the steps of: i) converting the compound of formula (II) to a compound of the formula (III) using TPP and sodium iodide in the presence of THF, water, and base; ii) reacting the compound of formula (III) with 4-methyl-5-formyl-thiazole to produce a compound of formula (IV); iii) deesterifying the compound of the formula (IV) to yield compound of formula (V); iv) converting the compound of formula (V) to compound of formula (VI) in the presence of a base and solvent; v) converting the compound of formula (VI) into compound of formula (VII) by enzymatic hydrolysis; and vi) reacting compound of formula (VII) with compound of formula (VIII) in the presence of solvent and base to produce compound of formula (I).

As a novel substance is provided such a new, crystalline substance of Cefditoren povoxyl which has a high purity and an enhanced thermal stability on storage. This crystalline Cefditoren pivoxyl may be prepared by a process comprising a step of dissolving amorphous substance of Cefditoren pivoxyl in an anhydrous, first organic solvent capable of dissolving said amorphous substance well therein, and steps of replacing the first organic solvent component of the resulting solution by an anhydrous alkanol of 1 to 5 carbon atoms as a second organic solvent, in such a manner that the firstly prepared solution of Cefditoren pivoxyl in the first organic solvent is mixed with a volume of the alkanol and then is concentrated below 15° C. under reduced pressure, and so on. Thereby, the process proceeds so as to produce a solution containing 50 mg/ml to 250 mg/ml of Cefditoren pivoxyl dissolved in the alkanol alone. From the latter solution, crystals of Cefditoren pivoxyl are induced to deposit by addition of water at a temperature of 0-10° C. The resulting admixture of the concentrated solution of Cefditoren pivoxyl in alkanol with added water and the deposited Cefditoren pivoxyl is then agitated 10° C. or below, to effect a complete crystallization of Cefditoren pivoxyl.

The invention belongs to the technical field of medicines and particularly relates to a preparation method of cefditoren pivoxil. The preparation method particularly includes following steps: (1) carrying out a reaction between cefditoren mother nucleus 7ATCA and AE-activated ester with dichloromethane as a solvent under an alkaline condition at 0-5 DEG C; (2) performing extraction with pure water and adding a sodium iso-octoate/acetone solution to obtain cefditoren sodium; (3) carrying out a reaction between the cefditoren sodium and iodomethyl pivalate under the alkaline condition at -40 DEG C to obtain a cefditoren pivoxil solution; (4) adding pure water to separate out a crystal to obtain a crude product of the cefditoren pivoxil. The technical scheme also comprises steps of dissolving the crude product of the cefditoren pivoxil in a mixed solution including dichloromethane and anhydrous ethanol, washing the material solution with a 1% sodium bicarbonate solution and pure water, collecting an organic phase, and performing a pressure-reducing evaporate-drying process to obtain the cefditoren pivoxil being higher than 99% in purity and less in impurities. The preparation method is simple in operation, is easy to control, is high in yield, allows the raw material to be obtained easily and is suitable for industrialized large-scale production.

Processes are provided for the preparation of orally administrable, yellow and powdery compositions essentially consisting of particles composed of a homogeneous mixture of an amorphous Cefditoren pivoxil substance with a water soluble high-molecular additive. These compositions can be produced by dissolving crystalline Cefditoren pivoxil substance and the water-soluble high-molecular additive in an aqueous solution of an acid, then neutralizing the resultant solution, to co-precipitate the product, and drying the thus precipitated product, followed by recovering the product in the form of the above-mentioned particles.

The invention discloses a preparation process of cefamandole nafate. The preparation process comprises steps of: heating and stirring 7-amino cephalosporanic acid, 5-mercapto-1-methyltetrazole and a catalyst boron trifluoride acetonitrile complex for a reaction; and carrying out a cooling post-treatment to obtain cefditoren nuclear parent; conducting a heating reflux reaction on the cefditoren nuclear parent and a silanizing agent until the solution turns to a clarified state; adding N, N-dimethyl aniline under the protection of inert gas at a low temperature, dropwise adding D-(-)-O-formyl mandeloyl chloride for reaction, and carrying out post-treatment to obtain formyl cefamandole acid; and reacting the formyl cefamandole acid with an organic acid salt, and recrystallizing to obtain the cefamandole nafate. By the above way, the preparation process of cefamandole nafate provided by the invention employs a simple and easily implemented process to obtain high-yield cefditoren nuclear parent with low impurity content; dichloromethane is used as a solvent to obtain the cefamandole acid with greatly enhanced color grade and yield; and dosage of activated carbon in the post-treatment is obviously reduced, so as to reduce the production cost.

The invention relates to a preparation method of Cefditoren Pivoxil. The preparation method comprises steps as follows: 7-ACA (3-acetyloxymethyl-5-thio-7-amino-8-oxy-1-nitrogen heterobicyclic octyl-2-ene-2 carboxylic acid) is taken as a starting raw material and is subjected to iodination and Wittig reaction after silanization protection, and a Cefditoren parent nucleus 7-ATCA (7-amino-3-[(Z)-2-(4-methyl-5-thiazole) vinyl]-3-cephem-4-carboxylic acid) is generated; after amino protection of aminothiazole ethyl gallate, a compound 2 is produced from 7-ATCA under catalysis of AlMe3; the compound2 is subjected to an esterification reaction with iodomethyl pivalate under actions of a phase transfer catalyst and an acid adsorbent, the amino protection is removed, and a target product CefditorenPivoxil is obtained. According to the preparation method, reaction conditions are mild, product purity and yield are high, the process is stable, amplification is easy, and the method is applicable to industrial production.

The invention discloses a method for preparing cefditoren pivoxil in the technical field of medicine, which comprises: dissolving a cefditoren pivoxi crude product in a water-soluble solvent; preparing a cefditoren pivoxil organic phase; preparing a cefditoren pivoxil aqueous phase; and adjusting the pH value of the solution, performing acid extraction treatment and menstruum crystallization treatment, and obtaining the cefditoren pivoxil with the purity of 98.1 to 98.8 percent. The method ensures that the cefditoren pivoxil can obtain high-purity products according with pharmacopoeia through purification under stable condition by simple operation.

The invention relates to a medicament composition and method of preparing the same. The medicament composition includes micronized particles of cefditoren pivoxil, wherein the particles have the d0.5 from 1[mu]m to 40 [mu]m. The invention also relates to method for preparing micronized cefditoren pivoxil particles.

The invention discloses a preparation method of a cefditoren pivoxil dimer. The preparation method is characterized in that an organic solvent and cefditoren sodium are added to a reaction container,and are stirred and dissolved, the temperature is reduced to subzero 20-subzero 50 DEG C, iodomethyl pivalate is added in batches, and iodomethyl pivalate is added again after reacting for a certain time after each addition of iodomethyl pivalate; inorganic or organic base is required to be added to control pH at 7.5-8.5 during the reaction, and subsequent separation and purification are performedafter the reaction to obtain the product. The preparation method has simple steps, simple raw materials and low cost, and is suitable for large-scale preparation. The content of the cefditoren pivoxil dimer prepared with the preparation method provided can reach 92.0% or higher, a theoretical basis is provided for safe use of drugs, effective data support is provided for the quality standard of cefditoren pivoxil, and effective guarantee is provided for safe clinical use of drugs.

The present invention provides a process for the preparation of Cefditoren of formula (I) which comprises acylating 7-amino-cephem carboxylic acids of the general formula (IV), where R3 is hydrogen or trimethylsilyl with thioester derivatives of the formula (II), where R1 represents C1-C4 alkyl or phenyl in an organic solvent in the presence of an organic base at a temperature in the range of -10 ° C. to 30 ° C.

The invention discloses odor-proof garment fabric. The odor-proof garment fabric is characterized by being prepared from raw materials in parts by weight as follows: 80-100 parts of 5-ethylene-2-thiazolamine/bis(triethoxysilyl)ethylene/4-vinylbenzeneboronic acid methyl iminodiacetate/tetrahydroxystilbeneglucoside/16,17-epoxy progesterone modified cefditoren parent nucleus/allyl cyclodextrin copolymer, 8-12 parts of amino-functionalized MOFs and 5-10 parts of pearl powder. The invention also discloses a preparation method of the odor-proof garment fabric. The disclosed odor-proof garment fabrichas good antibacterial and odor-proof effects, excellent comprehensive performance, good durability, washability and wear comfort, can realize good odor-proof effect, is good in washability, causes no damage to human bodies and ecological environments and has a healthcare function.

The present invention relates to a pharmaceutical composition comprising Cefditoren pivoxil, water soluble high molecular weight substance and one or more pharmaceutically acceptable excipient wherein weight ratio of high molecular weight substance to Cefditoren pivoxil is greater than 1:4 and a process for preparation thereof.

According to the present invention, there is provided a solid dispersion composition which can maintain amorphous cefditoren pivoxil in a suspension for a long period of time. The present invention is a solid dispersion composition comprising at least 0.1 mg of a sugar ester fatty acid on the basis of an amount equivalent to 100 mg efficacy of cefditoren pivoxil.

The invention belongs to the technical field of medicines, and particularly relates to a preparation method of high-purity cefditoren pivoxil. The preparation method comprises following specific steps: controlling the temperature of cefditoren sodium (1) and iodomethyl pivalate (2) to be -30 DEG C to-35 DEG C for reaction to obtain a cefditoren pivoxil (3) solution; extracting with an organic phase/water mixed solvent, washing with a 0.1% sodium bicarbonate aqueous solution, crystallizing with an organic phase inert solvent, and carrying out ethyl acetate crystal transformation purification onan obtained crude product to obtain the high-purity cefditoren pivoxil of which the purity is greater than 99.5% and the individual impurity content is less than 0.1%, thereby reaching the USP bulk drug standard of the variety. The technical scheme discloses in the invention further provides a refining method of cefditoren pivoxil, a crystalline cefditoren pivoxil product is obtained by directlydissolving and crystallizing with ethyl acetate, and the refining method is simple to operate, easy to control, high in yield, good in quality and suitable for industrial production.

The invention relates to the field of freeze-dried preparation for injection. The invention particularly discloses a cefditoren sodium freeze-dried preparation for injection and a preparing method thereof. The cefditoren sodium freeze-dried preparation for injection comprises cefditoren sodium, a dissolution-assisting agent and a proper amount of a pH regulator, wherein the dissolution-assisting agent is a mixture of arginine and citric acid. The cefditoren sodium freeze-dried preparation for injection adopts citric acid and arginine to be combined as the dissolution-assisting agent, and the dissolution-assisting agent has quite good dissolution-assisting property on cefditoren sodium, obviously improves the dissolution rate in water for injection, shortens the dissolution time, and improves the stability of the cefditoren sodium freeze-dried preparation; and the cefditoren sodium freeze-dried preparation can achieve the stability equal to the cefditoren sodium raw material.

The invention discloses a cefditoren sodium-containing pharmaceutical composition which is composed of cefditoren sodium and a cosolvent, the cosolvent is a mixture of arginine and a pharmacologically acceptable hydroxyl-containing solid organic acid, and the hydroxyl-containing solid organic acid has 4-12 carbon atoms. The cefditoren sodium-containing pharmaceutical composition compounds the hydroxyl-containing solid organic acid and the arginine to use as the cosolvent, and has a very good cosolubility, the concentration of the cefditoren sodium in an injection is improved, compared with cefditoren sodium raw material, the solubility of the cefditoren sodium-containing pharmaceutical compositioncan be as high as 554.8%; and at the same time, the stability of the cefditoren sodium-containing pharmaceutical composition is good and is equal to that of the cefditoren sodium raw material.

The invention relates to the technical field of synthesis of drug related substances, and particularly discloses a preparation method of E-type cefditoren sodium. The preparation method of the E-type cefditoren sodium comprises the following steps: cooling a mixed solution composed of water and acetone to 0-5 DEG C, adding E-type 7-ATCA and AE active ester, adjusting the pH value to 8-8.5 by using organic alkali, heating to 15-25 DEG C, reacting, and maintaining the pH value of the reaction solution at 8-8.5 in the reaction process; and after the reaction is finished, adding an acetone solution of sodium isooctoate, growing crystals, carrying out suction filtration, and drying to obtain the E-type cefditoren sodium. According to the preparation method of the E-type cefditoren sodium provided by the invention, the E-type cefditoren sodium with high purity and high yield can be obtained, the whole preparation method is simple to operate, the reaction condition is mild, and the finally obtained E-type cefditoren sodium completely meets the requirement of serving as a cefditoren pivoxil reference substance and has good application prospects. Important data support is provided for ensuring the quality detection of the cefditoren pivoxil.

The invention which belongs to the medicine processing field concretely relates to a synthetic technology of a cefditoren pivoxil intermediate. The synthetic technology of the cefditoren pivoxil intermediate provided in the invention has the advantages of simple operation, no pollution and high yield. The technology of the invention comprises the following steps: preparation of 2-amino-4-methyl-5-methylthiazole formate, preparation of 4-methyl-5-methylthiazole formate and preparation of 4-methyl-5-formylthiazole.