51 results about "Etimicin sulfate" patented technology

The invention relates to a continuous separation and purification method for etimicin sulfate by using the technology of continuous ion chromatography to realize high efficient separation of etimicin sulfate. The method comprises that the hydrolysate of synthesized etimicin sulfate is fed into a continuous ion chromatography system, through the steps of adsorption, removal of impurities by washing, elution of the etimicin sulfate, collection of the eluent, and regeneration of the chromatographic columns; and the etimicin sulfate is obtained through nanofiltration concentration, vacuum condensation under reduced pressure, and salt formation and decolourization of the collected eluent. By using the method for separation and purification, the obtained etimicin are of high yield and purity, low cost, and environmental protection, suitable for industrial production.

The invention discloses an etimicin sulfate preparation method. The etimicin sulfate preparation method includes the steps of protecting amino groups at 3, 2', 6' and 3' of gentamicin C1a with Fmoc-Cl and performing purification and evaporation to dryness to obtain quadrifluorenyl methoxycarbonyl gentamicin C1a; adding N-ethyl of an acetaldehyde aqueous solution under acidic conditions and performing reduction with sodium triacetoxyborohydride; finally adding a piperidine / DMSO (dimethylsulfoxide) solution for deprotection; performing secondary purification on an reaction solution with weakly acidic cation adsorption resin after performing primary purification on the reaction solution with a macroporous adsorption resin column and adding sulfuric acid to a purified product to obtain etimicin sulfate through reaction. The etimicin sulfate preparation method is high in selectivity and less in side reaction in group protecting, mild in reaction conditions, simple in operation and easy to perform industrial production during the whole reaction process and high in purity and yield of the product. (An equation as shown in the description).

The invention relates to a method for preparing Etimicin sulfate. In the method, under the action of a complex protective agent, gentamicin Cla is subjected to 1-N-ethylation, the synthesized product is separated by macroporous resin, the synthesized product is concentrated, the pH value of the synthesized product is adjusted by sulfuric acid to form a salt, the salt is decolorized by active carbon and freeze-dried; and the medicinal Etimicin sulfate meeting related standards is obtained. When the method is used for producing Etimicin sulfate, the synthesis process can be shortened greatly, the labor production efficiency is improved, and the discharge of waste water, gas and slag is reduced.

The invention discloses a method for preparing etimicin sulfate, and belongs to the technical field of medicines. The method comprises the steps of: adding copper acetate monohydrate into gentamicin C1a to form a copper ion complex; then adding a benzyl compound into a reaction system, controlling the temperature at 15-40 DEG C, and then adding alkali into the reaction system to react; decoppering and purifying the obtained reaction liquid so as to obtain a light yellow oily compound I; adding acetic acid into the oily substance, controlling the temperature at 5-15 DEG C, adding acetaldehyde to react for a while, adding a catalyst Pd / C and continuously filling hydrogen to react; and separating, purifying and acidizing the reaction liquid so as to obtain etimicin sulfate. The method of utilizing benzyl to protect amino groups is adopted, and high selectivity is obtained; and two reaction steps of reduction and deprotection are completed through a 'one-pot method', and the method is low in reaction temperature and takes a short period, thus, side reaction is less, purification is easy, the reaction and separation costs are lowered, and the method can be easily applied to industrial production.

The invention relates to a continuous-chromatography separating and purifying method of etimicin sulfate. Efficient separation of the etimicin is realized by virtue of a continuous-chromatography process. The continuous-chromatography separating and purifying method of etimicin sulfate comprises the following steps: introducing hydrolysate of the synthesized etimicin into a continuous-chromatography system, performing adsorption, impurity washing and elution on the etimicin, collecting eluant, performing chromatographic column regeneration, concentrating the collected eluant, and salifying and discoloring the concentrated eluant to obtain the etimicin sulfate. The etimicin sulfate separated by the method disclosed by the invention is high in yield, high in purity, low in cost, environmentally friendly and suitable for industrial production.

The invention belongs to the field of medicines and relates to a purifying method for etimicin sulfate. The purifying method for etimicin sulfate provided by the invention comprises the following steps: 1) taking an etimicin sulfate solution and concentrating into an etimicin sulfate concentrated solution; 2) adding dilute sulphuric acid into the etimicin sulfate concentrated solution, thereby obtaining an etimicin sulfate concentrated solution; 3) adding active carbon in the etimicin sulfate concentrated solution, heating, stirring and filtering, thereby obtaining an etimicin sulfate refined solution; 4) adding the etimicin sulfate refined solution in a solvent, and stirring, thereby obtaining a mother solution rich in seed crystals; 5) adding another batch of etimicin sulfate refined solution prepared according to the steps 1-3 in the mother solution rich in seed crystals obtained in the step 4, controlling the temperature and standing by, thereby obtaining a crystal mixture of the etimicin sulfate; 6) mashing and filtering the crystal mixture of the etimicin sulfate, thereby obtaining a wet crystal of the etimicin sulfate; and 7) drying the wet crystal of the etimicin sulfate, thereby obtaining a high-purity etimicin sulfate crystal.

The invention relates to an aminoglycoside compound and an extracting separation method thereof. The compound is separated from etimicin sulfate and has a following structural formula. The invention also relates to a separating method for the aminoglycoside compound.

The invention discloses a method for simultaneously separation determination of the content of three aminoglycoside antibiotics (AGs) (tobramycin, etimicin and netilmicin); the method successfully separates a mixture of the three antibiotics, and also is applied in determination of the content of the AGs in tobramycin eye drops, an etimicin sulfate injection and a netilmicin sulfate injection, and an HPLC-RRS combined technology is used for determination of the AGs. In an experiment, used chromatographic columns comprise Agilent Zorbox SB-C18 column (250 mm*4.6 mm i.d., 5 [mu]m) and a protective column (Security Guard C18, 4*2 mm, Phenomenex). A mobile phase is methanol:water (containing 0.2% TFA)=5:95 (v / v), the HPLC flow rate is 0.50 mL*min<-1>, [lambda]ex=[lambda]em=362 nm, the column temperature is 30 DEG C, and the sample injection volume is 20 [mu]L. The probe is a 2.0*10<-5> mol*L<-1> PSB solution, the pH is 9.5, the single-pump flow rate is 0.2 mL*min<-1>, the reaction pipe length is 250 cm, and the internal diameter is 0.5 mm. A brand-new HPLC detection mode established with RRS as a detection method is established, and is successfully applied to determination of the content of the AGs in different preparations. The application range of the RRS technology is widened, and the brand-new detection mode is provided for HPLC.

The invention relates to a quick central-control detection method for etimicin sulfate, wherein UPLC (Ultra Performance Liquid Chromatography) or UHPLC-ELSD (Ultra High Pressure Liquid Chromatography-Evaporative Light Scattering Detector) is employed, and separated and purified etimicin sulfate stripping liquid containing ethanol is taken as a sample and directly subjected to analysis, thereby controlling the production process. The method provided by the invention employs the technology of combining the ultra performance liquid chromatography with evaporative light scattering, and thereby is capable of realizing online quick detection in the production process; and therefore, the purpose of indicating flow component collection and detection in the separation and purification processes is achieved. Besides, the method is convenient, quick, accurate and reliable.

The invention discloses an etimicin sulfate pseudo-polymorph, and a preparation method and an application thereof. The X-ray powder diffraction pattern of the pseudo-polymorph has characteristic peaks appearing at 2theta having degrees of 5.1+ / -0.2, 6.0+ / -0.2, 7.0+ / -0.2, 7.6+ / -0.2, 8.5+ / -0.2, 10.9+ / -0.2, 12.5+ / -0.2, 13.1+ / -0.2, 13.7+ / -0.2, 15.5+ / -0.2, 16.0+ / -0.2, 16.6+ / -0.2, 17.2+ / -0.2, 17.6+ / -0.2, 19.4+ / -0.2, 19.9+ / -0.2, 20.1+ / -0.2, 20.5+ / -0.2, 21.7+ / -0.2, 22.6+ / -0.2, 23.2+ / -0.2, 24.0+ / -0.2, 24.5+ / -0.2, 26.0+ / -0.2, 26.7+ / -0.2, 27.1+ / -0.2, 27.6+ / -0.2, 28.4+ / -0.2 and 28.8+ / -0.2. The invention also discloses the preparation method of the pseudo-polymorph, and the application of the pseudo-polymorph in the preparation of medicines for treating human bacterial infectious diseases.

The invention discloses a near infrared spectrum online detection method of etimicin sulfate column separation process. The method of the invention comprises the following steps: (1) collecting different batches of eluant samples during the etimicin sulfate column separation process; (2) measuring contents of etimicin sulfate, C1a component and the like in the eluant samples by liquid chromatography or ion chromatography; (3) acquiring near infrared spectral data of the eluant samples; (4) establishing a key index rapid analysis model; and (5) rapidly measuring etimicin sulfate in unknown eluant samples, C1a component and liquid-phase total peak area. The near infrared spectroscopy technology is applied to the etimicin sulfate column separation process. In comparison with a traditional liquid phase and gas phase chromatography, the established analysis method of the invention is rapid and effective, can be used for rapidly measuring etimicin sulfate, C1a component and total matter quantity during the etimicin sulfate column separation process, and is suitable for real-time analysis and online monitoring during the production process of etimicin sulfate.

The invention provides an etimicin sulfate preparation method. The method comprises the following steps: taking gentamycin C1a base, dissolving the gentamycin C1a base in a certain proportion of a solvent, adding a certain proportion of a complexing agent to complex, adding a certain proportion of an amino group protection agent, keeping for a certain time, adding a certain proportion of a precipitating agent, stirring above materials, filtering the obtained mixture, adding a certain proportion of an acetylation reagent to the above obtained filtrate, reacting for a certain time, adding a certain proportion of a reducing agent, reacting for a certain time, removing an amino protection group, adding a certain proportion of water, carring out vacuum concentration under certain conditions to remove the solvent, adjusting the pH value with ammonia water, adsorbing with macro-porous resin, carrying out gradient separating purification with diluted ethanol, collecting an etimicin solution with a certain purity, carrying out vacuum concentration under certain conditions, adding sulfuric acid to adjust the pH value, adding a certain proportion of active carbon, decolorizing, filtering, and drying to obtain etimicin sulfate according with relevant standards.

The invention relates to a preparation method of etimicin sulfate. The preparation method includes following steps: taking gentamicin C1a base, dissolving in a solvent of a certain proportion, addinga complexing agent of a certain proportion, adding an amino protection agent of a certain proportion, maintaining for certain time, adding a solvent and ammonia water of a certain proportion, stirring, skimming, and concentrating to obtain a first intermediate; taking a reducing agent of a certain proportion, adding a solvent and acetic acid of a certain proportion, maintaining for certain time, adding the first intermediate, allowing reaction for a period of time, adding a strong alkaline solution to adjust pH, filtering, and concentrating to obtain a second intermediate; adding a solvent anda palladium carbon catalyst of a certain proportion, allowing reaction at certain hydrogen pressure and temperature, filtering, concentrating, using resin for adsorption, using ammonia water for resolving, concentrating, using sulfuric acid to adjust pH, removing carbon, filtering, and drying to obtain etimicin sulfate.

The invention provides an etimicin sulfate preparation method. The method comprises the following steps: 1, adjusting the pH value of an etimicin-containing crude solution having a concentration of 50-100mg / ml to 9.0-12.0 to obtain a mother solution; 2, adding the mother solution to a macro-porous adsorption resin column, eluting with water, a dilute sulfuric acid solution having a pH value of 2.5-3.0 and a dilute sulfuric acid solution having a pH value of 1.5-2.0 step by step, collecting, and concentrating to obtain a primary separation solution which is an etimicin sulfate solution having a concentration of 50-100mg / ml; and 3, adjusting the pH value of the primary separation solution to 10.0-11.5, adding the obtained solution to a reversed-phase adsorption resin column, eluting with water and the dilute sulfuric acid solution having a pH value of 1.5-2.0 step by step, collecting, concentrating to an etimicin sulfate solution having a concentration of 100-200mg / ml, and lyophilizing to obtain a refined product.

The invention relates to a synthesis method of an etimicin sulfate intermediate (3,2',6'-tri-N-acetyl gentamicin C1a). The synthesis method comprises the following steps: a, adding 20 L of methanol, 2.70 kg of gentamicin C1a and 3.21 kg of anhydrous zinc acetate into a 50 L three-port bottle at a temperature of 29 DEG C, stirring for 1.5 h to dissolve, and thus obtaining a gentamicin C1a-Zn complex; b, dripping 2.55 L of acetic anhydride into the complex of the step a for acetylation; c, after finishing the reaction, concentrating the reaction liquid of the step b, introducing the concentrated liquid into a chromatographic separation column for charging the sample, rinsing with a salt-free water, resolving with an ethanol water solution, and collecting effective components; concentrating, drying to obtain 3.29 kg of the finished product P1, wherein the yield is 95.3%, and the purity is 96.1%.

The invention discloses a method for multistage anaerobic treatment, which belongs to the field of wastewater treatment and aims to provide a treatment method for the production wastewater of etimicinsulfate, which effectively improves the treatment efficiency. The method is characterized in that the method comprises the following steps: step 1, the wastewater from etimicin sulfate production enters a hydrolysis acidification tank for acidification; step 2, effluent of the hydrolysis acidification tank enters a first stage anaerobic reactor; step 3, the effluent of the first stage anaerobic reactor overflows into an intermediate tank for the pH value adjustment; step 4, the effluent of the intermediate tank is divided into two parts, the first part flows into a multistage anaerobic reactor, and the overflow water from the top of the multistage reactor is the final effluent, the second part flows back to the hydrolysis acidification tank and is mixed with the etimicin sulfate production wastewater; operations of steps 1 to 4 are repeated. By adopting a hydrolytic acidification coupled tandem anaerobic reflow process according to the invention, an anaerobic biological treatment is performed on the etimicin sulfate wastewater, thereby greatly reducing COD and residual antibiotics in the wastewater.

The invention relates to aminoglycoside compounds and an extraction and separation method therefor. The compounds are separated from etimicin sulfate and have a structural formula as described in the specification. The invention also relates to a separation method for the aminoglycoside compounds.

The invention discloses a pharmaceutical composition of etimicin sulfate and application of the pharmaceutical composition in biomedicine. The pharmaceutical composition comprises the etimicin sulfate and a natural product compound (I) novel in structure; when in single action, the etimicin sulfate and the compound (I) have therapeutical effect in acute gouty arthritis; when the etimicin sulfate and the compound (I) are in combined action, therapeutical effect in acute gouty arthritis is further improved, so that the pharmaceutical composition can be developed into drugs for treating acute gouty arthritis; compared with the prior art, the pharmaceutical composition has outstanding substantive features and significant improvement.

The invention relates to an aminoglycoside compound and an extraction separation method thereof. The compound is obtained by being separated from an etimicin sulfate crude product and is named as 6''-N-ethylgentamicin C1a. The invention further relates to a separation method of the aminoglycoside compound.

The invention discloses an etimicin sulfate liposome inhalant and a preparation method thereof. The liposome inhalant is prepared from 1 part by weight of etimicin sulfate, 15-20 parts by weight of phospholipid, 125-150 parts by weight of a buffer solution and a proper amount of auxiliary materials. The pH value of the inhalant ranges from 6.2 to 6.4. The preparation method comprises the followingsteps of mixing the etimicin sulfate, the phospholipid and an organic solvent, performing dissolving, performing concentration to remove the organic solvent, adding the buffer solution, performing shaking slightly, and carrying out high-pressure homogeneous cutting to obtain etimicin sulfate liposome; and adding a proper amount of auxiliary materials, and performing dissolving, filtering and filling. The inhalant has an excellent targeting effect; compared with a common injection, the inhalant has the advantages that the bioavailability is higher, the concentration of drugs at toxic parts canbe reduced, and the safety of the drugs is greatly improved. The preparation method is simple and feasible and is suitable for industrial production.

The invention relates to an aminoglycoside substance and an extracting and separating method thereof. The compound is separated from etimicin sulfate, and has a structural formula shown in the specification. The invention further relates to a separating method of the aminoglycoside substance.

The invention discloses a synthetic method of etimicin sulfate. The synthetic method comprises the following steps: carrying out a reaction on gentamicin C1a, zinc acetate and acetic anhydride to obtain 3, 2', 6'-tri(N-acetyl) gentamicin C1a; after separating and purifying the 3, 2', 6-tri(N-acetyl) gentamicin C1a, carrying out a reaction with iodoethane to obtain 3, 2', 6'-tri(N-acetyl)-1-ethyl gentamicin C1a; hydrolyzing the 3, 2', 6'-tri(N-acetyl)-1-ethyl gentamicin C1a by sodium hydroxide to obtain an aqueous solution of etimicin sulfate; and carrying out HZD-2 macroporous resin adsorption, separation and purification, concentration, sulfate formation, decarburization and drying on the aqueous solution of etimicin sulfate to obtain an etimicin sulfate finished product. The method disclosed by the invention is high in yield which is 55%, and satisfies the requirements of Chinese pharmacopoeia (Edition 2010).

The invention relates to an aminoglycoside compound and an extraction separation method thereof. The compound is separated and obtained from a crude etimicin sulfate product and has a chemical structure as follows. The invention further relates to a separation method of the aminoglycoside compound.

The invention relates to an etimicin sulfate suppository as well as a preparation method and application thereof. The etimicin sulfate suppository is prepared from the following components in parts byweight: 50-500 parts of etimicin sulfate, 50-200 parts of an additive and 500-2000 parts of suppository matrix, and each suppository is 1-3g in weight.

The invention provides a preparation method of netilmicin sulfate freeze-dried powder injection, which comprises the following steps: a) mixing netilmicin sulfate, antioxidant, excipient and first water for injection, and performing pH value Adjustment and adsorption treatment to obtain a mixed solution A; b) mixing the mixed solution A with the second water for injection, followed by freezing treatment and drying treatment to obtain netilmicin sulfate freeze-dried powder injection; the first water for injection The mass ratio with the second water for injection is 8:(1-3). Compared with the prior art, the preparation method provided by the present invention obtains the netilmicin sulfate freeze-dried powder injection with good stability and high content of active ingredients. The experimental results show that after the netilmicin sulfate freeze-dried powder injection obtained by the preparation method provided by the present invention is stored for 24 months, the product has no color change, is stable for a long time, and the active ingredient content of the product is more than 95.30%.

The invention discloses an etimicin sulfate preparation method. The etimicin sulfate preparation method includes the steps of protecting amino groups at 3, 2', 6' and 3' of gentamicin C1a with Fmoc-Cl and performing purification and evaporation to dryness to obtain quadrifluorenyl methoxycarbonyl gentamicin C1a; adding N-ethyl of an acetaldehyde aqueous solution under acidic conditions and performing reduction with sodium triacetoxyborohydride; finally adding a piperidine / DMSO (dimethylsulfoxide) solution for deprotection; performing secondary purification on an reaction solution with weakly acidic cation adsorption resin after performing primary purification on the reaction solution with a macroporous adsorption resin column and adding sulfuric acid to a purified product to obtain etimicin sulfate through reaction. The etimicin sulfate preparation method is high in selectivity and less in side reaction in group protecting, mild in reaction conditions, simple in operation and easy to perform industrial production during the whole reaction process and high in purity and yield of the product. (An equation as shown in the description).

The invention discloses a pre-treatment method for improving anaerobic treatment efficiency of etimicin sulfate synthetic wastewater and belongs to the field of wastewater treatment. The invention aims at providing the pre-treatment method for the etimicin sulfate synthetic wastewater, which can be used for remarkably improving the subsequent treatment efficiency of an anaerobic reactor and can beused for greatly reducing COD (Chemical Oxygen Demand) of output water of the anaerobic reactor. According to the technical scheme, the pre-treatment method comprises the following steps: S1, inoculating anaerobic sludge into a pre-treatment tank; adding the etimicin sulfate wastewater into the pre-treatment tank; S2, adding K2HPO4 into the etimicin sulfate wastewater and intermittently stirringthe wastewater and the anaerobic sludge in the pre-treatment tank by utilizing a stirring machine; S3, taking each 8 hours as one cycle period in a pre-treatment process, wherein each cycle period canbe divided into three phases. The pre-treatment method disclosed by the invention is applicable to pre-treatment of the etimicin sulfate synthetic wastewater.

The invention relates to a method for synthesis of Etimicin sulfate intermediate 3, 2', 6'-tri-N-acetyl gentamicin Cla. The method consists of the following steps of: under certain temperature, reacting gentamicin Cla with zinc acetate in a methanol solvent to generate a complex, cooling the reaction solution and adding triethylamine, adding a tetrahydrofuran solution of acetic anhydride dropwisely for an acylation reaction, carrying out liquid phase tracking, and adding a sodium oxalate solution after completion of the reaction, filtering a zinc oxalate precipitate, delivering the filtrate to ion exchange resin, first conducting washing with pure water, then conducting washing with acid of certain concentration, adjusting the pH of the acid washed liquid to 9, performing concentration, adding ethanol to separate out a solid, implementing filtration, and freeze-drying the filtrate, thus obtaining the 3, 2', 6'-tri-N-acetyl gentamicin Cla.

The invention relates to an aminoglycoside compound and an extraction separation method thereof. The compound is obtained by being separated from an etimicin sulfate crude product and is named as 6''-N-ethylgentamicin C1a. The invention further relates to a separation method of the aminoglycoside compound.