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In a process for preparation of ceftriaxone sodium of formula (II), embedded image comprising the steps of i) reacting a silylated compound of formula (III), embedded image with a 4-halo-2-methoxyimino-3-oxo-butyric acid derivative of formula (IV), embedded image wherein X and Y represent a halogen atom to give a compound of formula (V), embedded image ii) desilylating the compound of formula (V), wherein X is as defined hereinabove to give the desilylated compound of formula (VI), embedded image iii) reacting the desilylated compound of formula (VI) with thiourea in a solvent system containing organic solvent and water, to obtain ceftriaxone of formula (I), embedded image iv) converting the compound of formula (I) to the sodium salt (II); wherefore the improvement comprises i1) reacting a silylated compound of formula (III),
embedded image with a 4-halo-2-methoxyimino-3-oxo butyric acid derivative of formula (IV), having a purity of at least 95% and containing di- and poly-brominated compounds less than 0.50%, embedded image wherein X and Y represent a halogen atom in the presence of an inert water-immiscible organic solvent or mixtures thereof and in the presence of an acid scavenging agent at a temperature of between -10° C. to -0° C. to give a compound of formula (V), embedded image ii1) adding the solution of compound of formula (V) in the inert water-immiscible organic solvent or mixtures thereof to a 1:1 mixture of water and a water-immiscible organic solvent and separation of the organic phase to provide a solution of compound of formula (VI) in the inert water-immiscible organic solvent or mixtures thereof, embedded image iii1) reacting the solution of compound of formula (VI) in the inert water-immiscible organic solvent or mixtures thereof with a solution of thiourea in water in the presence of an alkali metal containing inorganic base at a temperature of between 0° C. to +10° C. at a pH ranging between 5.0 to 5.5 and separation of the organic layer to provide a solution of the alkali metal salt of Ceftriaxone Sodium Crude of formula (II1) in water,
wherein M is an alkali metal, embedded image iv1) mixing the solution of the alkali metal salt of ceftriaxone (II'), wherein M is as defined hereinearlier in water with a water-immiscible organic solvent and a water-miscible solvent and treating the solution thus obtained with an acid to a pH of 3.6 to 4.0 and isolating the precipitated ceftriaxone of formula (I) by filtration, embedded image v1) reacting a solution of ceftriaxone of formula (I) in water with an organic amine maintaining a pH of 5.4±0.2 to produce a solution of the amine salt of ceftriaxone in water of formula (VII), embedded image wherein Q represents the organic amine, and vi1) reaction of the amine salt of ceftriaxone of formula (VII) in a mixture of water and a water-miscible organic solvent with a sodium metal carrier to give ceftriaxone sodium of formula (II), substantially free of impurities and having low Color absorbance. embedded image
Antibiotics for Prostate Infection:
1.Antibiotics used to treat prostate infections include oral drugs like trimethoprim-sulfamethoxazole, fluoroquinolones and doxycycline. In some cases, doctors prescribe an injection of the antibiotic ceftriaxone followed by an oral antibiotic, according to the U.S. National Library of Medicine.
2.Oral antibiotics usually require four weeks of treatment to completely rid you of a prostate infection. After an injection of ceftriaxone, only one week of oral antibiotics is needed, reports the U.S. National Library of Medicine.
3.Common side effects of antibiotics include upset stomach and diarrhea. Fluoroquinolones pose a risk for inflammation of the intestines, and some people develop serious allergic reactions to antibiotic drugs, cautions the Merck Manual.
It is commercially sold as the disodium hemiheptahydrate salt of formula (II), commonly referred to as ceftriaxone sodiums , under the brand names Rocefin® and Rocephin(e)®. embedded image
Ceftriaxone sodium is the largest-selling intravenous (iv) cephalosporin antibiotic worldwide and has been safely prescribed for over 15 years in both adults and children. This broad spectrum antibiotic exhibits remarkable activity against Gram-positive and Gram-negative bacteria, organisms responsible for the majority of community-based infections. These include upper and lower respiratory tract infections, including otitis media, sinusitis, bronchitis and community-acquired pneumonia as well as soft tissue infections. These infections result in nearly 80 million treated patients in the United States alone. Ceftriaxone is primarily used to treat hospital in-patients.
Because of its therapeutic and commercial importance, there is always a demand for a process for manufacture of ceftriaxone sodium manufacturer on industrial scale, which gives the product not only in high yield but also of superior quality and stability, thereby rendering it highly amenable for formulation into a suitable dosage form.
Ceftriaxone of formula (I) has generally been synthesised by two methods as described in the art. Both the methods involve amidification of the 7-amino function of 7-amino-3-[2,5-dihydro-6-hydroxy-2-methyl-5-oxo-as-triazin-3 -yl]-3-cephem-4-carboxylic acid derivative of formula (A) either directly with (Z)-2-(2-amino thiazol-4-yl)-2-methoxyimino acetic acid or its reactive derivatives thereof of formula (B) [Method—I] or with a (Z)-4-halo-2-methoxyimino-butyric acid derivative of formula (C) to give a 7-substituted cephalosporin addendum of formula (D), which on reaction with thiourea forms the (Z)-2-(2-amino thiazol-4-yl)-2-oxyimino acetamido side chain and thereby, provide ceftriaxone of formula (I), after necessary deprotections, if any of protective groups [Method—II]. The Ceftriaxone Sodium Crude (D) thus obtained is converted to the sodium salt of formula (II) by methods known in the art. The two methods of synthesis are summarized in Scheme—I.
In compounds of formula (A), (B), (C) and (D) of Method—I and II, the meanings of the groups R, R 1 and X are as defined therein and the groups Y and Z represent hydrogen or a group which forms a basis that compound of formula (B) and (C) are in a reactive form. source:bloggumceftriaxone
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