51 results about "Piperacillin" patented technology

Substituted bicyclic beta-lactams of Formula I: (I), are β-lactamase inhibitors, wherein a, X, R1 and R2 are defined herein. The compounds and pharmaceutically acceptable salts thereof are useful in the treatment of bacterial infections in combination with β-lactam antibiotics. In particular, the compounds can be employed with a β-lactam antibiotics (e.g., imipenem, piperacillin, or ceftazidime) against microorganisms resistant to β-lactam antibiotics due to the presence of the β-lactamases.

The invention involves antibiotic compound recipe containing piperacillin, sulbactam or clavulanic acid, ion chelator which can inhibit the formation of particles chelator, the recipe can be further added in buffering ingredient as stability system, the characteristics of the recipe is that it can be prepared to stable pharmaceutical solutions, and with aminoglycoside antibiotics in the same container are re-prepared to drugs used for complex anti-microbial infection.

The invention discloses a method for preparing piperacillin acid. The method comprises the following steps: adding ampicillin, water and a buffer solution with the pH of 6.0-9.0 into a reactor; adding EDPC into the reactor, meanwhile, adding an alkaline regulator to control the pH to be 6.0-9.0, and reacting for 30-60 minutes in the temperature range of 0 to 10 DEG C while carrying out heat preservation; and adding a solvent to crystallize, controlling the crystallizing point to be 15+ / -2 DEG C, dropwise adding an acidic regulator to regulate the end pH to be 1.5-2.0, carrying out crystal growing for 1 hour in the temperature range of 0 to 10 DEG C, and then, filtrating, washing and drying crystals, thereby obtaining the piperacillin acid finished product. According to the method, during acylation, water is used as a solvent, and the buffer solution is added, so that synthetic reaction for piperacillin acid is inhibited from going towards a reverse reaction direction, the yield of piperacillin acid is increased, and the purity of the product is improved.

The invention discloses a method for preparing 4-ethyl-2,3-dioxypiperazine-1-formate. In the method, 1-ethyl-2,3-dioxypiperazine and chloro-formate are used as raw materials and reacted in an organic solvent system in the presence of an acid binding agent to form 4-ethyl-2,3-dioxypiperazine-1-formate, wherein the molar ratio of the 1-ethyl-2,3-dioxypiperazine to the acid binding agent to the chloro-formate is 1:1.0-3.0:1.0-2.0; the chloro-formate is methyl chloroformate or ethyl chloroformate; and the 4-ethyl-2,3-dioxypiperazine-1-formate is 4-ethyl-2,3-dioxypiperazine-1-methyl formate or 4-ethyl-2,3-dioxypiperazine-1-ethyl formate. The method greatly reduces cost, simplifies process, reduces byproducts, improves product purity and reduces solvent separation processes; and the prepared product can be used as an intermediate for piperacillin and cefoperazone and is suitable for industrial production.

The invention discloses a method for detecting an antibacterial agent in serum by an ultra-high performance liquid chromatography-tandem mass spectrometry technology. The antibacterial agent containssulbactam (SBT), imipenem (IPN), linezolid (LNZ), melopenem (MPN), moxifloxacin (MXC), piperacillin (PRC), tigecycline (TGC), cefoperazone (CFZ), vancomycin (VCM) and teicoplanin (TCL). The method comprises the steps: detecting the content of the antibacterial drug in the pretreated serum by adopting an ultra-high performance liquid chromatography tandem mass spectrometry method, quantifying by utilizing a mass spectrometry isotope internal standard method, establishing a calibration curve by taking the concentration ratio of a standard substance to an internal standard substance as an X axisand the peak area ratio of the standard substance to the internal standard substance as a Y axis, and calculating the concentration of a target drug in the serum. According to the method, the pretreatment process is simple, the sensitivity is high, the specificity is high, separation and detection of the antibacterial agent are completed within 5 min, and a reliable detection method is provided for monitoring the treatment concentration of the antibacterial agent clinically.

The invention relates to a method for synthesizing 4-ethyl-(2, 3-dioxo)-1-piperazine formyl chloride, which comprises the following steps: using 4-ethyl-2, 3-dioxopiperazine as a starting raw material, di-(trichloromethyl) carbonate as a formyl chloridizing reagent, trimethyl chlorosilane as an activator and a prptectant, triethylamine as an acid-binding agent and a catalyst which are reacted with each other to prepare the 4-ethyl-(2, 3-dioxo)-1-piperazine formyl chloride; and adding crystallizing agents such as n-hexane, petroleum ether, hexamethyl disiloxane, dipropyl ether, cyclohexane into a reaction liquid of the 4-ethyl-(2, 3-dioxo)-1-piperazine formyl chloride to separate out 4-ethyl-(2, 3-dioxo)-1-piperazine formyl chloride crystal. The method for synthesizing and crystallizing the 4-ethyl-(2, 3-dioxo)-1-piperazine formyl chloride provides a more appropriate intermediate for producing piperacillin and cefoperazone, and can shorten the synthesizing process and improve the quality thereof.

The invention discloses an injection of a piperacillin-sulbactum sodium medicine composition injection and a preparation method thereof. The injection disclosed herein comprises 1-10 weight parts of piperacillin, 0.5-5 weight parts of sulbactam sodium, 0.4-8 weight parts oflactose, 0.4-8 weight parts of sodium chloride and a proper amount of sodium dihydrogen phosphate for adjusting the pH value of the solution to 7.0. The preparation method comprises the following steps: weighing piperacillin, sulbactam sodium, lactose, and sodium chloride based on the weight parts, using water for injection to dissolve, using the sodium dihydrogen phosphate for adjusting the pH value of the solution to 7.0, then diluting with water for injection to obtain 5000 ml of medicine solution; and filtering the medicine solution by a filtering membrane, drying, conducting sterile crushing, and filling to obtain the injection. According to the invention, the injection has the advantages of high solubility, good stability, etc.

The invention discloses application of ursolic acid in inhibiting growth of multi-drug-resistance enterobacter cloacae. According to a good in-vitro killing function of ursolic acid upon anthropogenic multi-drug-resistance enterobacter cloacae which resists to cefazolin, cefotaxime, aupmentn, meropenem, ofloxacin, levofloxacin, ciprofloxacin, cefoxitin, minocycline, imipenem, piperacillin, azithromycin and macrodantin, growth of multi-drug-resistance enterobacter cloacae can be inhibited, the lowest sterilization concentration is 0.6mg / mL, and the lowest antibacterial concentration is 0.3mg / mL. The invention discloses an inhibition function of the ursolic acid upon the multi-drug-resistance enterobacter cloacae, and the ursolic acid is capable of effectively alleviating or solving the drug-resistance infection problem of the multi-drug-resistance enterobacter cloacae and reducing the case fatality rate, provides new ideas for inhibiting anthropogenic multi-drug-resistance enterobacter cloacae, and has great practical significances.

The invention relates to a piperacillin induced hemolysis detection reagent kit and a method for preparing the same. The piperacillin induced hemolysis detection reagent kit comprises piperacillin inducible hemolysis detection reagent cards I, piperacillin inducible hemolysis detection reagent cards II, piperacillin treated red blood cells, non-piperacillin treated red blood cells, antibody positive control liquid and antibody negative control liquid. The piperacillin treated red blood cells are normal O Rh (rhesus) negative red blood cells treated by piperacillin medicine solution; the non-piperacillin treated red blood cells are normal O Rh negative red blood cells with the concentration of 2-2.5%; the piperacillin antibody positive control liquid is piperacillin antibody positive serum; the piperacillin antibody negative control liquid is piperacillin antibody negative serum. The piperacillin induced hemolysis detection reagent kit and the method have the advantages that the piperacillin inducible hemolysis detection reagent kit is high in sensitivity, good in repeatability and stable in quality, detection procedures are short in time consuming, the method is simple, convenient and feasible, and results are easy to judge.

The invention relates to an antibiotic compound containing piperacillin, sulbactam or clavulanic acid, and an ionic chelating agent capable of inhibiting particle generation. The compound can be further added with a buffer component as a steady system. The compound is characterized by being prepared into a steady solution preparation and prepared into a medicine for resisting microbial infection together with aminogylcoside antibiotics in the same container.

The invention discloses a preparation method of piperacillin acid and aims to overcome the defect that existing preparation methods are low in N-ethyl dioxperazine conversion rate and the defect of high solvent consumption caused by the fact that the condensation step generates non-condensable gas-carbon dioxide. Pyridine is adopted to replace triethylamine as an acid binding agent, and 4-dimethylaminopyridine in a catalysis amount is added as an initiator before triphosgene is added during acylation reaction, so that reaction activity of triphosgene can be improved effectively, and conversionrate of N-ethyl dioxypiperazinyl chloride is increased by about 10%. During condensation reaction, binary weak alkali like calcium carbonate is used to replace unitary weak alkali-sodium hydrogen carbonate, so that reducing of degradation is facilitated, condensation reaction yield is increased about 5%, and yield of the non-condensable gas-carbon dioxide can be reduced by 50%.

The invention discloses piperacillin-sulbactam sodium medicinal composition liposome injection and a preparation method thereof. The liposome injection comprises the following components in part by weight: 4 parts of piperacillin, 1 part of sulbactam sodium, 2.5 to 7.5 parts of liposome carrier and 0.2 to 1 part of freeze-drying supporting agent, wherein the liposome carrier is the combination of the sitosterol and octadecylamine, preferably the combination of the sitosterol and octadecylamine in a weight ratio of 3:1; and the freeze-drying supporting agent is the combination of mannitol and lactose, preferably the combination of the mannitol and lactose in a weight ratio of 2:1; or the liposome injection comprises the following components in part by weight: 2 parts of piperacillin, 1 part of sulbactam sodium, 1.5 to 4.5 parts of liposome carrier and 0.1 to 0.6 part of freeze-drying supporting agent, wherein the liposome carrier is the combination of sitosterol and phosphatidyl ethanolamine, preferably the combination of the sitosterol and phosphatidyl ethanolamine in a weight ratio of 5:8; and the freeze-drying supporting agent is the combination of nucleo-glycan and sodium alginate, preferably the combination of the nucleo-glycan and sodium alginate in a weight ratio of 3:1.

The invention discloses an injection of a piperacillin-sulbactum sodium medicine composition and a preparation method thereof. The injection disclosed herein comprises 10-15 weight parts of piperacillin, 2.5 weight parts of sulbactam sodium, 2-5 weight parts of lactose, 1 weight part of sodium chloride, and 0.1-0.5 weight parts of sodium citrate. The preparation method comprises the following steps: weighing piperacillin, sulbactam sodium, lactose, and sodium chloride based on the weight parts, using water for injection to dissolve, preparing sodium citrate into a 0.1mol / L solution by using water for injection, adding the 0.1mol / L solution dropwisely to the solution obtained by dissolving and stopping adding dropwisely when the pH value is 6.8, and then dilute with water for injection to make 5000mL to obtain a colorless and transparent medicine solution; filtering the medicine solution by a filtering membrane, drying, conducting sterile crushing, and filling to obtain the injection. According to the invention, the injection has the advantages of good stability, fast dissolving speed, etc.; and the preparation method has simple operation, reduces production cost, and is suitable for large-scale production.

The invention discloses an application of citral in inhibiting growth of multi-drug resistant enterobacter cloacae. The citral can inhibit growth of multi-drug resistant enterobacter cloacae as the citral has relatively good in vitro killing action to multi-drug resistant enterobacter cloacae resisting cefazolin, cefotaxime, augmentin, meropenem, ofloxacin, levofloxacin, ciprofloxacin, cefoxitin, minocyline, imipenem, piperacillin, azithromycin, macrodantin, sulfamethoxazole and nalidixic acid. The minimum bactericidal concentration is 1.6 mg / mL and the minimal inhibitory concentration is 1.0 mg / mL. The invention provides inhibiting action of citral to multi-drug resistant enterobacter cloacae and the citral has wide application value in the field of medicine.

The invention relates to a preparation method of a piperacillin monoclonal antibody and application. A hybridoma cell strain is utilized for preparation. The preparation method comprises the followingsteps: preparing a piperacillin monoclonal antibody, performing antibody purification, performing antibody purity identification and performing antibody titer identification. The prepared piperacillin monoclonal antibody is used for detecting piperacillin drug antibodies. Blood of a detected object serves as a detection sample, if the piperacillin antibody exists in plasma, the antibody is boundto a piperacillin drug antigen on piperacillin treated cells by virtue of anti-IgG+G3d bridging so as to produce agglutination, the antibody cannot pass through a gel space and remains on the upper layer of the gel or is dispersed into the gel under the effect of centrifugal force, and presents a positive reaction; and if any antibody does not exist in the plasma or the cell surface does not contain any drug antigen, agglutination is not produced, and the antibody can pass through the gel space to deposit at the bottom of a micro-column gel hole under the effect of the centrifugal force and presents a negative reaction.

The invention provides a piperacillin-containing composition. The composition contains piperacillin and also contains ampicillin and sulbactam in a certain ratio. The invention also provides a pharmaceutical preparation and application thereof. The composition and the pharmaceutical preparation which are provided by the invention can obviously inhibit drug-resistant acinetobacter baumannii, especially have good treatment effect on infection of the acinetobacter baumannii resistant to carbapenem antibiotics or cefoperazone sulbactam and has obvious clinical advantage.

The invention discloses a method of increasing the genetic transformation efficiency of medicago sativa. The method includes (1) a step of seeding and culturing medicago sativa; (2) a step of preparing a microbe solution, namely a step of picking a single agrobacterium colony containing an Medtr4g107010.1 gene, subjecting the colony to overnight culture in a YEP medium, performing centrifugation, collecting microbe solution sediment, and suspending the collected agrobacterium solution until OD<600> is 0.8-0.9 by utilizing an MS liquid medium; and (3) a step of genetic transformation, namely a step of cutting off blades of medicago sativa aseptic seedlings, putting the obtained blades into an MS medium, culturing the blades in a tissue culture room, then infecting explants in the microbe suspension, then transferring the explants to an MS medium, performing dark culture, then transferring the explants to a selective medium containing 250 mg / L of piperacillin, and culturing the explants in the tissue culture room. The method is advantaged by significantly promoting regeneration of adventitious buds, rapidly and efficiently preparing transgenic plants and increasing the transformation efficiency.

The invention discloses a kit used for detecting beta-lactamase in dairy and a detection method thereof. The kit is composed of two parts of a detection main body and a detection reagent, the detection main body is a coated 96 orifice plate containing detection thalline, a soda acid indicator and nutrients required for thalline growth, and the detection reagent is an organic solution containing beta-lactam antibiotics. The detection thalline is a bacillus stearothermophilus suspension; the soda acid indicator is bromcresol purple, and the detection reagent is piperacillin dissolved by acetonitrile. The kit is based on a microbe growth inhibition factor releasing method, color change can reflect the microbe growth state, so that the beta-lactamase content case in milk can be indirectly displayed. The kit has the characteristics of simple operation, rapidity, high efficiency and accuracy, and has characteristics of low equipment requirement, no requirement for professional operation, clear result interpretation.

The invention provides a compound pharmaceutical composition containing piperacillin and its application. In the compound pharmaceutical composition, piperacillin and avibactam are used as active ingredients, and both piperacillin and avibactam are in solid form exist. The pharmaceutical composition of the present invention has excellent antibacterial activity, especially has good effect on drug-resistant Streptococcus pneumoniae, and improves the efficacy by dozens of times compared with the existing piperacillin product.

The invention discloses application of sanguinarine in inhibiting growth of multi-drug-resistant enterobacter horbiae. The sanguinarine has a good in-vitro killing effect on the multi-drug-resistant enterobacter horbiae of piperacillin, levofloxacin, bromgrantine, imipenem, ofloxacin, furadantin, cefathiaquine, azithromycin and naphthyridine acid, and can inhibit the growth of the multi-drug-resistant enterobacter horbiae, the minimum inhibitory concentration is 0.12 mg / mL, and the minimum bactericidal concentration is 0.24 mg / mL. The invention provides the inhibition effect of the sanguinarine on the multi-drug-resistant enterobacter horbiae, and the sanguinarine has wide application value in the fields of medicines and the like.

A preparation method of traditional Chinese medicine lotion for treating low-temperature-form ecthyma belongs to the technical field of a preparation method of traditional Chinese medicine. At present, low-temperature-form ecthyma is generally treated by antibiotics and sulfonamides, intramuscular injection of piperacillin sometimes can cause local pain, and fast venous push injection can cause temporary nausea, choking sensation in chest, cough, fever, bad smell in mouth, conjunctival injection and other bad influence. The technical scheme is that soaking common monkshood mother root, slender root of Common Monkshood, monkshood, Manchurian wild ginger, pepper, fructus piperis longi, piper cubeba, Foeniculum vulgare, fragrant-flowered garlic, rhizoma galangae, fructus cnidii, hot pepper, caraway, resurrection lily rhizome, Sabia japonica, caulis piperis futokadsurae, caulis trachelospermi, herba aristolochiae, Common herons Bill herb, peach kernel, red flower, Salvia Miltiorrhiza, moutan bark, fructus evodiae and liquorice in water and decocting the 25 medicines with mild fire, and the decocted decoction is the traditional Chinese medicine lotion for treating low-temperature-form ecthyma. The preparation method has the advantages that the prepared traditional Chinese medicine is small in toxic and side effects, short in course of treatment and high in cure rate and further can avoid the bad influences caused by taking of western medicine.

The invention discloses a piperacillin impurity and a preparation method thereof. The piperacillin impurity is shown as a formula (I); the piperacillin impurity is used as an impurity in a piperacillin synthesis process and appears in a piperacillin product. The preparation method of the piperacillin impurity comprises the following steps: taking piperacillin as a raw material; after dissolving with water and sodium bicarbonate, adding ethanol and reacting; after reaction is finished, dropwise adding an acid solution to adjust the pH (Potential of Hydrogen) to be equal to 1.5 to 3.0; filteringa separated-out product; adding water into a filter cake and dissolving; then cooling and separating out to obtain a piperacillin impurity crude product; then carrying out liquid chromatography separation and organic solvent extraction to obtain an impurity solution with the purity which is greater than or equal to 99 percent. According to the piperacillin impurity disclosed by the invention, anunknown impurity in the piperacillin RRT equal to 1.75 is synthesized and purified and an obtained impurity pure product is analyzed to determine the structure of the impurity; the impurity is a product obtained by carrying out opening ring ester formation on the piperacillin and ethanol and has no toxicity. The structure confirmation of the impurity and the preparation of the impurity pure product play an important role in quality control of the piperacillin. The formula (I) is shown in the description.

The invention provides a compound pharmaceutical composition containing piperacillin and applications thereof. The active component of the compound pharmaceutical composition is composed of piperacillin and avibactam, and piperacillin and avibactam are both in a solid form. The provided pharmaceutical composition has excellent antibacterial activity and very good effect on killing drug resistant streptococcus pneumonia. Compared with a conventional piperacillin product, the curative effect is improved by dozens of times.

The invention provides a piperacillin-containing composition. The composition contains piperacillin and a certain proportion of ampicillin and sulbactam. The invention also provides its pharmaceutical preparation and application. Compositions and pharmaceutical preparations of the present invention can significantly inhibit drug-resistant Acinetobacter baumannii, especially to carbapenem antibiotics or cefoperazone-sulbactam-resistant Acinetobacter baumannii infection can play a significant role. Good therapeutic effect, with significant clinical advantages.

The invention provides a preparation process and a dose detection device of penicillin drugs for injection. Firstly, the standard dose height after the standard dose of penicillin preparations are filled into the vials and shaken to level off is determined; then the first dose is determined based on the standard dose line height. Preset height; during the subpackaging process of penicillin preparations, use a laser inspection system to detect the highest height of the powder pile formed after penicillin preparations are filled into vials to obtain the first actual height; when the first actual height is lower than At the first preset height, an alarm is given, or the vial is marked or picked out. The invention realizes the on-line dose detection of the piperacillin, ampicillin and other series of penicillin injection sterile powder packaging products, and can quickly detect the products with obviously insufficient filling dose, thereby reducing the defective rate of the products.

The invention discloses a synthesizing method of 4, 4'-carbonyl di-1-ethyl piperazine-2, 3-dione. The method comprises the following steps: firstly carrying out reaction on 4-ethyl-2, 3-dioxopiperazine and a silylating reagent in an organic solvent; and then carrying out condensation reaction with 4-ethyl-2, 3-dioxo-piperazine acyl chloride under an alkaline condition to obtain 4, 4'-carbonyl di-1-ethyl piperazine-2, 3-dione. The invention further provides a refining method of 4, 4'-carbonyl di-1-ethyl piperazine-2, 3-dione. The methods disclosed by the invention are high in product purity, simple in process, high in yield and suitable for industrial production. The 4, 4'-carbonyl di-1-ethyl piperazine-2, 3-dione obtained provides a high purity reference substance (the purity is over 98%) for production of 4-ethyl-2, 3-dioxo-piperazine acyl chloride or piperacillin and meanwhile, the 4, 4'-carbonyl di-1-ethyl piperazine-2, 3-dione can be used as a commercial organic chemical intermediate to be sold.