50 results about "Micafungin" patented technology

This invention relates to a method of treating otitis externa, and in particular otitis externa of fungal etiology, using topical medication, including antifungal agents such as, for example fluconazole, voriconazole, itraconazole, clotrimazole, amphotericin B, caspofungin (Cancidas®), micafungin (Mycamine®), terbinafine, naftifine, butenafine, amorolfine, ravuconazole, posaconazole, flucytosine, econazole, enilaconazole, miconazole, oxiconazole, saperconazole, sulconazole, terconazole, tioconazole, nikkomycin Z, anidulafungin (LY303366), nystatin, pimaricin, griseofulvin, ciclopirox, haloprogin, tolnaftate, and undecylenate.

The invention discloses a preparation method for a micafungin precursor compound by using a Coleophoma sp. fermentation culture. The method comprises the following steps: carrying out filtration, digestion, resin adsorption, desorption, condensation and the like on the Coleophoma sp. fermentation culture so as to obtain a crude extract of FR901379; and carrying out further purification on the crude extract of the FR901379 by using silica gel chromatography so as to obtain a micafungin precursor compound FR901379 product with high purity. The invention has the following advantages: resin adsorption and silica gel chromatography are used to extract and separate the FR901379 in the method to prepare the micafungin precursor compound FR901379 with high purity, and the method is simple and feasible and is suitable for industrial production.

The present invention relates to a purification salt conversion method of micafungin. According to the present invention, the method is mainly characterized in that a buffer solution of a corresponding salt and a micafungin N, N-diisopropylethylamine salt are subjected to ion exchange on a reverse phase preparative chromatographic column so as to complete salt conversion, remove the related impurities, and achieve the purification effect; and the process has characteristics of stable and controllable process, easy and convenient operation, easy industrial production achieving, and easy product quality control.

The invention provides a micafungin parent nucleus producing bacterium strain and a method for producing micafungin parent nucleus by adding a micafungin precursor and carrying out deacylation on the micafungin precursor in the fermentation process, belonging to the field of biopharmacy. The method comprises the following steps: fermenting a micafungin parent nucleus FR179642 strain in a culture medium, wherein a micafungin precursor FR901379 is added twice in the fermentation process, and a multistage temperature control process is adopted, thereby enhancing the yield of the micafungin parent nucleus FR179642; and carrying out acidifying wall breaking treatment on the fermentation liquid, extracting with an organic solvent, carrying out macroporous resin adsorption-desorption to obtain a desorption solution, and crystallizing the desorption solution to obtain the micafungin parent nucleus powder. The method can be used for synthesizing the micafungin parent nucleus FR179642, and has the advantages of simple operating procedure, high stability and favorable reproducibility.

The invention provides a preparation method of micafungin precursor. The preparation method includes steps of producing strain spore suspension liquid through a few amounts of micafungin precursor and cultivating, and adding oxygen carrier in the fermentation liquid during the fermenting process, thus the dissolved oxygen concentration in a fermentation cylinder is improved, and 20-40% of output of the micafungin precursor is improved; performing the acidification and wall breaking treatment on the fermentation liquid, absorbing polar solvent by macroporous resin, analyzing and obtaining desorbed solution of micafungin precursor; crystalizing the desorbed solution and obtaining micafungin precursor powder. The invention can be used for compounding the micafungin precursor, and is simple in operation procedure, stable in method, good in reproducibility, and very suitable for industrial production; meanwhile, the method avoids using acetone and other poisonous solvent and lightens hazard to environment and human body.

The invention relates to a method for preparing a pharmaceutical intermediate, in particular to a method for synthesizing and purifying a micafungin intermediate. The method comprises the following steps: subjecting a compound II to a carboxylic acid group acylation reaction to obtain a compound III, subjecting the compound III and a compound IV to a condensation reaction, and carrying out crystallization purification to obtain a high-purity micafungin intermediate I. The preparation method provided by the invention has the advantages of simple process, cheap reagents, low solvent consumption, greatly reduced production cost, and higher purity and yield of products, and easy realization in industrial production.

The present invention provides a medicinal composition containing micafungin or a pharmaceutically acceptable salt thereof and trehalose as a stabilizing agent.

The invention discloses a saccharomyces cerevisiae strain with excellent autolysis resistance, and belongs to the field of molecular biology and microbiology. The strain is preserved in China General Microbiological Culture Collection Center (CGMCC) on September 1, 2014, the Preservation No. is CGMCC No. 9628, and the preservation address is Institute of Microbiology at the Chinese Academy of Sciences, at No.3, Courtyard No.1, Beichen West Road, Chaoyang District, Beijing. Compared with original strains, the thickness of cell walls of the strain is doubled, the strain can tolerate a starvation culture for 24 h in a mixture of 50 ng / mL of micafungin, 8% of ethanol, 0.4 M NaCl and sterile water, and autolysis simulation experiment data and scanning electron microscope results (60 h) show that the autolysis of recombinant strains is superior to that of original strains. The strain disclosed by the invention provides a new thought for the better control and utilization of an autolysis phenomenon of saccharomyces cerevisiae, and the obtained strain has a good application value in the aspects of improving the properties such as flavor, foam stability and the like of beer.

The invention discloses a drug composition containing micafungin or a salt thereof, wherein a polysaccharide or a disaccharide or a mixture of a polysaccharide and a disaccharide is adopted as an excipient, and the drug composition can contain a suitable amount of a pH value regulation agent. In addition, stability and potential safety of the drug composition of the present invention are superior to stability and potential safety of the existing preparation.

The present invention provides a liquid medicinal composition containing micafungin or a pharmaceutically acceptable salt thereof and a stabilizing agent.

The present invention relates to an improved process for the preparation of Micafungin.

The invention discloses a drug composition of micafungin or a salt thereof, wherein a polysaccharide or a monosaccharide or a mixture of a polysaccharide and a monosaccharide is adopted as an excipient, and the drug composition can contain a suitable amount of a pH value regulation agent. In addition, stability and potential safety of the drug composition of the present invention are superior to stability and potential safety of the existing preparation.

The invention relates to a solid phase-liquid phase full synthetic method for preparing micafungin. The method comprises that Fmoc-P-CTC resin serves as a carrier, a solid phase polypeptide synthetic method is adopted to gradually couple amino acid with an Fmoc protecting group from the C end to the N end, and then the protecting group is deprived through splitting, intramolecular reaction and liquid phase condensation to obtain the micafungin. The method is high in yield, brings convenience to aftertreatment and provides a new thinking way for industrial scale production of the micafungin.

The invention provides a preparation method of an intermediate for synthesis of a side chain of micafungin and a derivative thereof. The method is realized by reaction of an alpha, beta-unsaturated ketone compound in the presence of N-hydroxy-para toluene sulfonamide and inorganic base. Defects of the prior art can be overcome, the reaction conditions are mild, no expensive reagents are needed in the whole reaction process, the reaction router is shorter, the intermediate compound for synthesis of the side chain of micafungin can be prepared conveniently, and the reaction yield is high.

The invention discloses a preparation method of immobilized cyclic lipopeptide deacylase. A cyclic lipopeptide deacylase solution is directly mixed with a porous hydrophily enzyme carrier without purification, one or more kinds of organic solutions and inorganic salt are added, and then the immobilized cyclic lipopeptide deacylase is obtained. The invention further discloses application of the method in industrial production of micafungin parent nucleuses and anidulafungin parent nucleuses. The preparation method is simple in technology, enzyme purification equipment is omitted, the recovery rate of enzyme activities is obviously increased in the immobilization process, and immobilized enzymes can be repeatedly used. The enzyme method for converting micafungin and anidulafungin intermediates has higher concentration of reaction substrates when compared with a fermentation conversion method, a few product impurities are generated, and the conversion efficiency is high.

The invention discloses a high-purity micafungin or a salt thereof, and a preparation method and an application thereof. The content of a residual organic solvent in the micafungin or the salt thereofis lower than 1.8%. Air with a certain humidity is introduced into a drying box during preparation,, a raw material containing micafungin or the salt thereof is put into the drying box, and the raw material a water system undergo vacuum drying, and when the humidity of the drying box reaches 70% or above, air introduction is stopped. The preparation method has the advantages of mild conditions, simple operation process, high yield, good stability and convenient transportation of the product, great reduction of the technological operation difficulty coefficient, and reduction of the productioncost. The micafungin or the salt thereof can be used for preparing medicines for preventing or treating diseases caused by fungal infection.

The invention provides a high-yield strain of FR901379, the strain is Coleophoma empetris H40-23, the strain is preserved in China General Microbiological Culture Collection Center (CGMCC), the preservation number is CGMCC No.40075, the preservation date is Institute of Microbiology, Chinese Academy of Sciences, No.3, No.1 Yard, Beichen West Road, Chaoyang District, Beijing, the telephone number is 010-64807355, and the preservation number is CGMCC No.40075. The invention also provides a method for preparing the high-yield strain of FR901379. The invention also provides an application of the strain in production of the FR901379.

The invention provides a preparation method of a micafungin derivative side chain intermediate. The method is a preparation method of the micafungin derivative side chain intermediate, and the micafungin derivative side chain intermediate is prepared by directly taking monoterephthalate as a raw material. The process route is greatly shortened, toxic and high-pollution noble metal catalysts are prevented from being prepared and used, impurities difficult to remove are prevented from being generated due to excessive reaction, the process is simple, few equipment is occupied, operation is easy and convenient, and the method is suitable for industrial application.

The invention relates to a solid phase-liquid phase full synthetic method for preparing micafungin. The method comprises that Fmoc-P-CTC resin serves as a carrier, a solid phase polypeptide synthetic method is adopted to gradually couple amino acid with an Fmoc protecting group from the C end to the N end, and then the protecting group is deprived through splitting, intramolecular reaction and liquid phase condensation to obtain the micafungin. The method is high in yield, brings convenience to aftertreatment and provides a new thinking way for industrial scale production of the micafungin.

The invention belongs to the technical field of medicines, and in particular relates to an anti-infection micafungin freeze-drying composition and a preparation method thereof. The anti-infection micafungin freeze-drying composition mainly consists of active components micafungin, mannitol, meglumine and a pH adjusting agent. The anti-infection micafungin freeze-drying composition provided by the invention is stable in quality and free of conspicuous light degradation phenomenon after being diluted, so that convenience can be brought to clinical medical operators to prepare medicines, and use security to patients can be improved.

The present invention relates to a method for the purification of Micafungin.

The invention discloses a preparation method for a micafungin precursor compound by using a Coleophoma sp. fermentation culture. The method comprises the following steps: carrying out filtration, digestion, resin adsorption, desorption, condensation and the like on the Coleophoma sp. fermentation culture so as to obtain a crude extract of FR901379; and carrying out further purification on the crude extract of the FR901379 by using silica gel chromatography so as to obtain a micafungin precursor compound FR901379 product with high purity. The invention has the following advantages: resin adsorption and silica gel chromatography are used to extract and separate the FR901379 in the method to prepare the micafungin precursor compound FR901379 with high purity, and the method is simple and feasible and is suitable for industrial production.

The present invention provides simple, cost effective, rapid, and scalable at industrial scale and provide high purity and yield of Echinocandin-type compounds at low cost as compared to prior art. Moreover the process allows for the removal of impurities by using economical salt-adsorbent complex and provide highly purified Echinocandin type compounds which is highly improved in terms of purity and sufficient for further processing to obtain an active pharmaceutical ingredient such as, the antifungals caspogungin, anidulafungin, and micafungin.

The present invention provides a medicinal composition containing micafungin or a pharmaceutically acceptable salt thereof and trehalose as a stabilizing agent.

The invention belongs to the field of drug synthesis, relates to a preparation method of a high-purity micafungin intermediate, and concretely relates to a preparation method of a micafungin intermediate compound represented by formula A-4. The synthesis method is simple to operate and high in yield, and can meet the requirements of industrial production.

The present invention relates to an improved process for the preparation of Micafungin.

The invention discloses a preparation method of a high-purity micafungin precursor FR901379. The preparation method of the high-purity micafungin precursor FR901379 comprises the following steps: filtering a micafungin precursor fermentation leaching solution through a ceramic membrane, and performing adsorbing through macroporous adsorption resin, and performing desorbing. and concentrating the desorption solution, extracting and washing crystals by using a polar solvent to obtain a micafungin precursor crude extract, separating the crude extract by using polymer nano silica gel, removing thepolar solvent from the separated micafungin precursor FR901379 main component, and carrying out freeze-drying to obtain a high-purity micafungin precursor FR901379 product. The method has the effectsthat the high-purity micafungin precursor product can be obtained, the operation process is simple, the quality is high, and the solvent is easy to recover.