- Purification of amoxicillin trihydrate by impurity-coformer complexation in solution
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In this work, we demonstrated the purification of amoxicillin trihydrate (AMCT) by the formation of 4-hydroxyphenylglycine (4HPG)-coformer complex in solution. Without advanced knowledge of cocrystal formation of 4HPG, a workflow was established to choose
- Hsi, Kay Huai Ying,Concepcion, Anthony Joseph,Kenny, Meghan,Magzoub, Amna Ahmed,Myerson, Allan S.
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- Amoxicillin Inactivation by Thiol-Catalyzed Cyclization Reduces Protein Haptenation and Antibacterial Potency
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Serum and cellular proteins are targets for the formation of adducts with the β-lactam antibiotic amoxicillin. This process could be important for the development of adverse, and in particular, allergic reactions to this antibiotic. In studies exploring protein haptenation by amoxicillin, we observed that reducing agents influenced the extent of amoxicillin-protein adducts formation. Consequently, we show that several thiol-containing compounds, including dithiothreitol, N-acetyl-L-cysteine, and glutathione, perform a nucleophilic attack on the amoxicillin molecule that is followed by an internal rearrangement leading to amoxicillin diketopiperazine, a known amoxicillin metabolite with residual activity. Increased diketopiperazine conversion is also observed with human serum albumin but not with L-cysteine, which mainly forms the amoxicilloyl amide. The effect of thiols is catalytic and can render complete amoxicillin conversion. Interestingly, this process is dependent on the presence of an amino group in the antibiotic lateral chain, as in amoxicillin and ampicillin. Furthermore, it does not occur for other β-lactam antibiotics, including cefaclor or benzylpenicillin. Biological consequences of thiol-mediated amoxicillin transformation are exemplified by a reduced bacteriostatic action and a lower capacity of thiol-treated amoxicillin to form protein adducts. Finally, modulation of the intracellular redox status through inhibition of glutathione synthesis influenced the extent of amoxicillin adduct formation with cellular proteins. These results open novel perspectives for the understanding of amoxicillin metabolism and actions, including the formation of adducts involved in allergic reactions.
- Ariza, Adriana,Blanca, Miguel,Ca?ada, F. Javier,Monta?ez, María I.,Pérez-Sala, Dolores,Pajares, María A.,Sánchez-Gómez, Francisco J.,Torres, María J.,Zimmerman, Tahl
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- Preparation method of amoxicillin
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The invention provides a preparation method of amoxicillin. The amoxicillin is obtained by synthesis of amino protected raw materials, the reaction route is short, product purity is high, operation iseasy, and wide industrial application prospects are achieved.
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- Pharmaceutical Composition for the Eradication of Helicobacter Pylori and Preparation Method Thereof
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The present invention relates to a pharmaceutical composition and its preparation method for the eradication of Helicobacter pylorif in the forms of effervescent tablet, suspension or powder. The pharmaceutical composition comprises an effective dose of β-lactam antibiotic, an effective dose of macrolide antibiotic, an effective dose of antacid such as proton pump inhibitor and H2 blocker, and a pharmaceutical acceptable carrier. An effective dose of alkaline substance such as carbonate or bicarbonate can be added to increase the pH of the stomach when the PPI antacid is used, which can protect the degradation of acid-labile antibiotics or PPI to further increase the bioavailability of the pharmaceutical composition for the purpose of Helicobacter pylori eradication.
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- Process and device for producing liquid dosage formulations of medicinal compounds on demand from tablets and capsules
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The present invention provides a process for preparing liquid pharmaceutical formulations on demand from tablets and capsules.
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- Method of using deuterated calcium channel blockers
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Therapeutic methods and compositions using deuterated enriched 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester and other deuterated dihydropyridine compounds are described. The deuterated compounds exhibit enhanced efficacy in blocking calcium channels over non-deuterated dihydropyridines.
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- Pharmaceutical formulations containing clavulanic acid and an antibacterial agent
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A method of use of clavulanate to enhance the antibacterial activity of an antibacterial compound against microorganisms having an antibiotic resistance mechanism other than β-lactamase enzyme mediated resistance. Pharmaceutical formulations and methods of use which exploit this method.
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- Penicillin acylase in the industrial production of β-lactam antibiotics
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Immobilized penicillin acylase is a biocatalyst suitable for the kinetically controlled industrial synthesis of semi-synthetic antibiotics in aqueous environments. Amoxiciliin and ampicillin are obtained by condensing 6-aminopenicillanic acid with the amide or ester of D-( - )-4-hydroxyphenyIglycine and D-( - )phenylglycine, respectively. Similarly, the cephalosporin antibiotics cefadroxil and cephalexin can be obtained from 7-aminodesacetoxycephalosporanic acid.
- Brugging, Alle,Roos, Eric C.,De Vroom, Erik
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p. 128 - 133
(2013/09/08)
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- Enhancement of the efficacy of nifedipine by deuteration
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A method of enhancing the efficiency and increasing the duration of action of drugs (e.g. dihydropyridines and anti-bacterials) and particularly of nifedipine and penicillins wherein one or more hydrogen atoms are deuterated and wherein the deuterated drug has unexpectedly improved properties when used in much lower concentrations than unmodified drug. A method for determining the identity and bioequivalency of a new drug is also disclosed wherein the molecular and isotope structure of a new drug is determined by isotope ratio mass spectrometry and compared with the molecular and isotope structure of a known human drug.
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- Pharmaceutical thermal infusion process
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A chewable tablet comprises a medicament dispersed in a chewable base, such as mannitol, together with an effervescent couple, such as citric acid--sodium bicarbonate. The combination of effervescence and chewability with optional flavorings improves the taste characteristics of the medicament in oral administration. A distintegrant such as microcrystalline cellulose may be added to give the patient the option of dispersing the tablet in water.
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- Receptor conjugates for targeting penicillin antibiotics to bacteria
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A variety of conjugates useful for the treatment of infections due to pathogenic microorganisms are provided. The conjugates comprise at least one agent coupled to a receptor which binds a microorganism. Suitable agents include anti-infectives, such as antibiotics and synthetic drugs. The present invention also provides methods for treating infections in warm-blooded animals due to pathogenic microorganisms.
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- Prodrug derivatives of carboxylic acid drugs
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Novel ester derivatives of carboxylic acid medicaments of formula (I), wherein R--COO--represents the acyloxy residue of a carboxylic acid drug or medicament, n is an integrer from 1 to 3, and R1 and R2 are the same or different and are selected from a group consisting of an alkyl, an alkenyl, an aryl, an aralkyl, a cycloalkyl and which group may be unsubstituted or substituted, or R1 and R2 together with the N forms a 4-, 5-, 6- or 7-membered heterocyclic ring, which in addition to the nitrogen atom may contain one or two further heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and which heterocyclic group may be substituted. These compounds are highly biolabile prodrug forms of the corresponding carboxylic acid compounds and are highly susceptible to undergoing enzymatic hydrolysis in vivo whereas they are highly stable in aqueous solution. The novel derivatives are less irritating to mucosa than the parent carboxylic acids and may provide an improved bio-availability of the drugs.
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- Pharmaceutical tablet, pharmaceutical granulate and process for their preparation
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A pharmaceutical tablet containing an amphoteric beta-lactam antibiotic, microcrystalline or micro fine cellulose or a mixture of both and a second disintegrant, being low-substituted hydroxypropylcellulose, which fully disintegrates in water within 60 seconds. When swallowed it shows a bioavailability as good as a pharmacy prepared suspension of the antibiotic. The tablet is compressed from a mixture containing a new granulate which is prepared from the antibiotic substance, microcrystalline and/or micro fine cellulose and water only. Such tablets can also be prepared by using other known tablet disintegrants as the second disintegrant.
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- High yield process for preparing beta-lactam antibiotics having a high purity degree
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A high yield process for preparing beta-lactam antibiotics having a high purity degree, in particular derivatives of the cephalosporanic and penicillanic acids, of the formula: STR1 by condensation of the compounds STR2 where X=H --OCH3 (suitably blocked), with a chloride of the formula STR3 wherein R=H, OH in which said condensation is carried out in the presence of a nicotinic or isonicotinic base.
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- α-Keto aldehydes as enhancing agents of gastro-intestinal drug absorption
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A method and drug form enhancing the absorption of a rectally or orally administered drug from the rectal compartment into the blood stream of a warm blooded animal. The method includes the steps of preparing a drug form capable of being rectally and orally administered. The drug form comprises a therapeutically effective unit dosage amount of a selected drug of the type which is capable of being absorbed into the blood stream from the gastrointestinal area and an α-keto aldehyde or salts thereof being present in the drug form in a sufficient amount to be effective in enhancing the drug absorption rate, when administering the drug form to warm blooded animals.
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- Process for preparing cephalosporanic acid compounds
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A process for the preparation of [D-α-amino-p-hydroxyphenylacetamido]-penicillanic acid or cephalosporanic acid compounds comprising reacting a compound having a formula selected from the group consisting of STR1 wherein X is selected from the group consisting of hydrogen, acetoxy and five-membered heterocyclic group containing at least one hetero atom of the group consisting of oxygen, sulfur and nitrogen and optionally substituted with e.g. lower alkyl, this residue being attached to the 3-CH2 group via sulfur atom and wherein a NH radical if present has optionally been silylated with at least one mole equivalent of a silylating agent producing STR2 wherein R1, R2 and R3 are individually selected from the group consisting of lower alkyl, benzyl, cycloalkyl and phenyl in an inert anhydrous, organic solvent, preferably a water-inmiscible organic main-solvent, to form a compound having a formula selected from the group consisting of STR3 adjusting the pH to a scale value of 5.5 to 7.5 and reacting the resulting compounds in a pre-cooled solution with an at least equimolar amount of a compound of the formula wherein R4 is lower alkyl, R5 is selected from the group consisting of hydrogen and lower alkyl and R6 and R7 are lower alkoxy.
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- Process for the production of 6-D-α-amino-p-hydroxyphenylacetamido penicillanic acid
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Process for the production of 6-D-α-amino-p-hydroxyphenylacetamido penicillanic acid which is a potent antibiotic also known generically as amoxicillin. According to the process there is reacted a boron derivative of 6-APA with an acylating agent derived from the D(-)-p-hydroxyphenylglycine, in dimethylformamide or in dimethylsulfoxide in admixture with methylene chloride or chloroform, hydrolyzing and then removing the enaminic group.
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- Process for preparing aminopenicillins
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An improved process for the preparation of α-amino-penicillins from an aqueous solution of a derivative of 6-APA and amide-type Dane salts.
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- Process for the production of penam and cephem derivatives
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A process for the preparation of penam and cephem derivatives by reacting a phosphite amide of a 6-aminopenicillanic acid or 7-aminocephalosporanic acid with an acyl halide in an aprotic solvent in the presence of a phosphite halide scavenger.
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- Process for the preparation of hydroxy-alpha-amino-benzyl penicillin
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A novel process for the preparation of hydroxy-alpha-amino-benzyl penicillin, particularly the p-hydroxy derivative known as amoxicillin.
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- β-Lactam antibiotic esterification process using methoxymethyl methane sulfonate
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Disclosed is an improved process for esterifying carboxylic acids, particularly 3-carboxylic acid groups of penicillins and 4-carboxylic acid groups of cephalosporins, to form methoxymethyl esters. Replacement according to the present process of the conventional halomethyl methyl ether esterifying agent with methoxymethyl mesylate avoids the carcinogenicity problem of the prior art reagent while still giving good yields of high quality product.
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- 6-(D-α-Amino-p-hydroxyphenylacetamido)-penicillanic acid preparation
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A process for the preparation of 6-(D-α-amino-p-hydroxyphenylacetamido)-penicillanic acid or amoxicillin by reacting 6-aminopenicillanic acid with at least two equivalents of a silylating agent producing trimethylsilyl groups in an anhydrous, inert, water-insoluble organic solvent and reacting the resulting product at a temperature below -25° C with an at least equimolar amount of a compound of the formula STR1 wherein R1 and R7 are lower alkoxy, R2 is lower alkyl and R3 is selected from the group consisting of lower alkyl and hydrogen previously prepared from the corresponding Dane salt and an acid chloride under anhydrous conditions in the presence of a tertiary amine in an inert, water-insoluble organic solvent.
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