36 results about "Fidaxomicin" patented technology

The invention discloses an Actinoplanessp. strain and its use in preparation of fidaxomicin. The Actinoplanessp. strain is entophytic Actinoplanessp. N12W0304, is preserved in the China general microbiological culture collection center (CGMCC) on December 26, 2012 and has a preservation number of CGMCC No.7043. A fidaxomicin production process comprises the following steps of preparing an Actinoplanessp. N12W0304 seed solution and fermentation broth, carrying out centrifugation of the fermentation broth to obtain mycelia, carrying out extraction, condensation, dissolution, filtration, resin adsorption and drying of the mycelia to obtain a fidaxomicin crystal crude product, dissolving the fidaxomicin crystal crude product, and carrying out liquid chromatographic separation and pressure-reduction drying of the solution to obtain a fidaxomicin refined product. Under the fermentation conditions, the Actinoplanessp. strain has a fidaxomicin fermentation unit which is more than 1400mg/L and is higher than the fidaxomicin fermentation yield reported at present. The fidaxomicin fermentation process provided by the invention is simple, is suitable for industrial production and realizes a total product yield of 60%.

The invention discloses a method for separating and purifying fidaxomicin from fidaxomicin fermented mycelia. The method comprises the following steps of first filtering and extracting the fidaxomicin fermentation liquid, diluting the extracted liquor with water, then decoloring, adsorbing and analyzing the extracted liquor through macroporous resin, and concentrating, extracting and drying the analyzed liquor to obtain a fidaxomicin crude product; and dissolving the fidaxomicin crude product in a polarity organic solvent, injecting polymer microsphere columns to carry out the chromatographic separation to obtain the high-purity fidaxomicin fine powder. By adopting the method, the interference of fermented secondary metabolite can be effectively eliminated, and the quality and the yield of the fidaxomicin can be improved. The entire process is simple and easy to operate; the prepared fidaxomicin can be used for drugs; and the purity of the prepared fidaxomicin is more than 95 percent, and the whole-coarse total yield is more than 45 percent. The used solvent is a conventional solvent, small in toxicity and applicable to the industrial production.

The invention provides a method for separating and purifying fidaxomicin. The method comprises the following steps: taking the C8 reverse phase silica gel as the filling material, carrying out column chromatography, dissolving fidaxomicin by acetic acid, loading the solution into the column, eluting the solution by a mobile phase, and collecting the sample; after the separation and purification, the HPLC purity of fidaxomicin is not less than 99.5%, and the content of a single impurity is not larger than 0.10%. The provided purification method of fidaxomicin adopts a novel medium having high selectivity and high capacity, thus the column has a high efficiency, the resolution is high, the separation and purification effect is better, the retention time is shorter, the elution agent using amount is less, and moreover the shortages that the fidaxomicin purity is low and the fidaxomicin quality is bad due to the low column efficiency and bad separation degree are overcome.

The invention relates to the field of pharmaceutic preparations, in particular to a solid dispersion of fidaxomicin serving as a treating medicament for a disease caused by clostridium difficile and a preparation method for the solid dispersion. The fidaxomicin solid dispersion is solid powder obtained by highly dispersing fidaxomicin into enteric-soluble or water-soluble carrier material, so that the solubility of the fidaxomicin at the small intestine part is greatly improved; compared with a commercially available oral tablet, the fidaxomicin solid dispersion has the advantages of good antibacterial effect, long acting time and little side effect. A medicine composition containing the fidaxomicin solid dispersion provided by the invention is high in solubility and high in stability; the preparation process is simple, the quality is stable, and the fidaxomicin solid dispersion is suitable for industrial production.

The invention discloses a fidaxomicin crystal and a preparation method of the crystal. Characteristic peaks, expressed by 2 theta, of an X-ray powder diffraction spectrum of the crystal are located at 3.324, 7.745, 9.989, 1.607, 13.954, 14.475, 15.355, 15.855, 18.800, 19.999, 20.321, 22.245, 23.104, 24.028 and 24.446. The method comprises the preparation steps of dissolving fidaxomicin in an aqueous solution of alcohol, crystallizing, conducting suction filtration, drying, and obtaining the fidaxomicin crystal. The preparation method has the advantages that the preparation method is stable in process and simple and quick to operate, facilitates environmental protection, and is appropriate to industrial production. The obtained fidaxomicin is stable in crystal form and uniform in particle, and facilitates subpackage and storage.

The present invention relates to pharmaceutical compositions for rectal administration comprising fidaxomicin and to a process for preparing the pharmaceutical compositions for rectal administration. The invention also relates to an aerosol canister comprising a foamable pharmaceutical composition comprising fidaxomicin for rectal administration and to the treatment or maintenance of remission of infections such as diarrhea caused by Clostridium difficile.

The invention discloses a stable fidaxomicin medicine composition, which is characterized in that a recipe for preparing 1000 tablets comprises the following ingredients including 200 to 400g of fidaxomicin, 70 to 140g of microcrystalline cellulose, 0.5 to 1g of superfine silica gel powder, 50 to 100g of croscarmellose sodium and a proper amount of 10-percent amylum pregelatinisatum solution. The invention also relates to a preparation method of the stable fidaxomicin medicine composition. The fidaxomicin prepared by the recipe and the preparation method has the advantages of high dissolution rate, high bioavailability and good curative effect.

The invention discloses an application of fidaxomicin in preparing medicines for treating related diseases and/or symptoms caused by dengue virus infection. The fidaxomicin, as a clinically approved drug for resisting clostridium difficile infection, is high in safety; and in addition, the fidaxomicin, which is high in activity of inhibiting the dengue virus infection and relatively strong in binding capacity with dengue virus non-structural protein NS5, is expected to function as a novel drug for resisting the dengue virus infection.

The invention discloses a method for preparing fidaxomicin by flash chromatography. The method comprises the following steps: firstly, extracting fidaxomicin fermentation mycelia with 60 to 80 percent ethanol, roughly separating extract liquid through polystyrene resin, and collecting a fraction which contains fidaxomicin; then, performing reverse-phase bonding silica gel rapid column chromatography separation twice on the fraction, wherein elution solvents of different selectivity are adopted; finally obtaining a non-fidaxomicin refined product of which the purity is over 98.5 percent. By adopting the method, the purity and yield of the obtained fidaxomicin are high; moreover, the method is relatively easy to operate, is relatively low in cost, and is suitable for industrial production.

The invention discloses a fidaxomicin crystal form II and a preparation method thereof. An X-ray powder diffraction spectrum of the crystal formula has X-ray powder diffraction peaks at 2theta, namely 7.04 degrees, 15.87 degrees, 19.14 degrees, 20.46 degrees and 22.95 +/-0.2 degrees. The crystal form obtained by the method is stable, simple in preparation method, strong in maneuverability and applicable to industrial production.

The invention discloses a fidaxomicin crystal form I and a preparation method thereof. An X-ray powder diffraction spectrum of the crystal form has X-ray powder diffraction peaks at 2theta of 4.22 degrees, 7.60 degrees, 8.17 degrees, 9.51 degrees, 10.07 degrees, 11.07 degrees, 11.51 degrees, 12.85 degrees, 13.28 degrees, 15.47 degrees, 16.24 degrees, 18.55 degrees, 19.78 degrees, 20.15 degrees, 20.80 degrees and 21.47 degrees. The crystal form provided by the invention is stable, simple in preparation method, strong in maneuverability, and applicable to industrial production.

The invention discloses application of fidaxomicin to preparation of a product for inhibiting activity of mycobacterium abscessus. The invention provides application of fidaxomicin or a pharmaceutically acceptable salt thereof or a substance taking the fidaxomicin or the pharmaceutically acceptable salt thereof as an active ingredient in preparation of a product for inhibiting activity of mycobacterium abscessus. According to the invention, the anti-mycobacterium abscessus activity of fidaxomicin is determined by adopting a microwell plate double dilution method, and the result shows that fidaxomicin has better bacteriostatic activity on a mycobacterium abscessus standard strain and clinically separated mycobacterium abscessus; new application of fidaxomicin in prevention and treatment of mycobacterium abscessus infection diseases is expected to be explored.

The invention discloses a preparation method of a macrolide compound OP-1118. The method comprises the following steps: a, reacting fidaxomicin in alkaline solution to obtain a reaction product; b, dissolving the reaction product obtained in the step a in an organic solvent to obtain a sample liquid; and c, conducting chromatography on the sample solution in a C18 medium pressure column to obtain a macrolide compound OP-1118 with purity more than 98.5%. The preparation method of the invention has the advantages of simple operation and high sample recovery rate, and is applicable to industrialization production.

The invention discloses an application of fidaxomicin in preparation of a product for resisting mycobacterium fortuitum infection. The invention provides an application of fidaxomicin or a pharmaceutically acceptable salt thereof or a substance taking the fidaxomicin or the pharmaceutically acceptable salt thereof as an active ingredient in preparation of a mycobacterium fortuitum bacteriostatic agent. According to the invention, the anti-mycobacterium fortuitum activity of the fidaxomicin is determined by adopting a microwell plate double dilution method, and the result shows that the fidaxomicin has relatively good bacteriostatic activity on mycobacterium fortuitum standard strains and clinically separated mycobacterium fortuitum; new application of fidaxomicin in prevention and treatment of accidental mycobacterium infection diseases is expected to be explored.

The invention discloses a pharmaceutical composition containing fidaxomicin and a preparation method thereof. The preparation method comprises the following steps: preparing granules containing fidaxomicin by adopting wet process granulation; and compacting the granules into the pharmaceutical composition. According to the composition containing the fidaxomicin disclosed by the invention, throughimproving the water addition amount in a wet process granulation procedure, the stirring velocity during granulation and the time required for wet process granulation, even if under the case of no adding an antioxidant, the prepared composition containing the fidaxomicin has high stability, less increase of related substances, meets the quality standard of drugs, can reduce a requirement on a temperature in a storage step and is stable in dissolution.