- Preparation method of piperacillin
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The invention discloses a preparation method of piperacillin. According to the method, DBU with stronger alkalinity is used as an initiator to promote the reaction of N-ethyl-2, 3-dioxopiperazine andtriphosgene to obtain N-ethyl-2, 3-dioxopiperazine acyl chloride, so that the use of trimethylchlorosilane is avoided; In the condensation reaction, sodium acetate is used as an acid-binding agent, sothat the pollution of carbon dioxide to the environment is avoided. The alkalinity of sodium acetate is weaker than that of sodium bicarbonate, the hydrolysis degree in the reaction process is low, meanwhile, DBU is used as a catalyst, and the N-ethyl-2, 3-dioxopiperazine acyl chloride hydrolysate can also react with ampicillin to obtain piperacillin, so that the reaction yield is increased, andthe production cost is further reduced.
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Paragraph 0028-0029; 0031-0032; 0034; 0035; 0037; 0040; 0042
(2021/02/06)
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- Preparation method of piperacillin acid
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The invention relates to the technical field of preparation methods of medicines and provides a preparation method of piperacillin acid, aiming at the problems of an existing preparation method of lowyield and low productivity. The preparation method comprises the following steps: S1, dissolving solid phosgene; S2, carrying out silanization on dioxypiperazine; S3, carrying out acyl chlorination;S4, dissolving ampicillin trihydrate; S5, carrying out condensation reaction; S6, carrying out hydrolysis reaction. According to the preparation method, a side chain of the piperacillin acid is formedthrough the silanization of the dioxypiperazine and the acyl chlorination; then the side chain and the ampicillin trihydrate are condensed to form piperacillin; meanwhile, rare-earth metal platinum is added into the condensation reaction and is used as a catalyst; only a trace amount of the catalyst needs to be added and a good catalysis effect can be realized, so that a reaction speed is increased; meanwhile, the purity and yield of the condensation reaction are easy to improve, so that the yield and purity of the piperacillin acid which is finally obtained through hydrolysis are easy to improve.
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- A method for preparing paipai pulls the xilin acid (by machine translation)
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The invention discloses a method for preparing paipai pulls the xilin acid. The invention is directed to preparation method in the prior existing "N - ethyl hydrogen peroxide piperazine conversion is relatively low, a condensation step the non-condensable gas carbon dioxide, solvent loss is relatively large" disadvantages, this invention adopts the pyridine in place of the triethylamine as acid, in the acylation reaction of adding triphosgene is added a catalytic amount of 4 - dimethyl amino pyridine as an initiator, can effectively improve the reaction activity of the triphosgene, so that the N - ethyl hydrogen peroxide piperazine acyl chloride conversion is improved by about 10%. The invention in the condensation reaction, binary weak alkali such as for calcium carbonate to replace the one dollar weak alkali sodium bicarbonate, help to reduce the degradation, condensation reaction yield is improved by about 5%, at the same time can reduce the generation of carbon dioxide gas causes non-condensable 50%. (by machine translation)
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Paragraph 0028; 0030-0031; 0033-0034; 0036-0037; 0039; 0041
(2019/05/22)
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- Piperacillin sodium compound containing half water
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The invention discloses a piperacillin sodium compound containing half water and a preparation method thereof. Each mole of piperacillin sodium contains a half mole of water. First, ampicillin trihydrate is reacted with 4-ethyl-2,3-dioxypiperazine formyl chloride to form piperacillin acid, then piperacillin acid is reacted with sodium acetate in a mixed solution of acetone and water, isopropanol is added dropwise, and crystallization, filtration and drying are conducted to obtain the piperacillin sodium compound containing half water. The piperacillin sodium compound containing half water hashigh fluidity, low hygroscopicity and impurity content, high thermodynamic stability and a wider application prospect.
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Paragraph 0029-0031; 0037-0039
(2019/01/23)
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- In vitro and in vivo evaluation of positively charged liposaccharide derivatives as oral absorption enhancers for the delivery of anionic drugs
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Oral delivery of hydrophilic, ionisable drugs remains a major challenge in drug development and a number of active pharmaceuticals fail to reach the market of oral drugs because of a lack of absorption and/or stability issues. One possible approach to improving the bioavailability of such drug candidates is to increase their lipophilicity, which is a key parameter in the permeation across cell membranes. However, modifying the chemical structure by adding lipid residues often results in changes in activity. With ionised molecules, ion-pairing can be considered to associate charged lipid moieties with the parent drug without altering its structure and therefore activity. This study presents the results of in vitro and in vivo evaluation of a series of synthetic, positively charged liposaccharide derivatives combined with an anionic model drug, piperacillin. The antimicrobial activity, plasma stability, Caco-2 cell permeability and oral absorption of the conjugates were assessed. Increases in apparent permeability were observed in vitro for three of the tested formulations, while retaining the antibacterial activity of the drug. However, the in vivo intestinal absorption of piperacillin formulated with the liposaccharide derivatives was found unchanged, possibly due to molecular dissociation, early degradation or structural differences between the intestinal epithelium and cultured monolayers.
- Bergeon, Julie A.,Ziora, Zyta M.,Abdelrahim, Adel S.,Pernevi, Niklas U.,Moss, Anne R.,Toth, Istvan
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experimental part
p. 2333 - 2342
(2011/03/21)
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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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- 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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- 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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