50 results about "Oritavancin" patented technology

The invention provides a preparation method of high-purity oritavancin key intermediate A82846B. The preparation method comprises the following steps: separating the oritavancin key intermediate A82846B from a fermented solution, first adjusting a pH, purifying by virtue of macroporous resin, then purifying by virtue of inversed phase chromatography, and finally crystallizing to obtain the high-purity A82846B. The method adopted by the invention is simple in operation, less in consumption of organic solvent, and capable of greatly reducing the generation of waste liquid; and moreover, the defects in the prior art that the adsorption efficiency of cation macroporous resin is low and the product yield is reduced due to the leaked adsorption can be overcome, and the preparation method is suitable for the industrialized production.

The invention provides a purification method of an Oritavancin intermediate A82846B. Specifically, the method comprises the following steps: loading an A82846B fermentation broth to an ion exchange resin chromatography column, and carrying out elution separation to obtain a first eluate; loading the first eluate toa reversed phase chromatography chromatography column with silica gel C18 or polystyrene polymer as a filler, carrying out impurity elution, carrying out sample elution and collecting a second eluate. Purity of the obtained A82846B is greater than 80%. By the method, quality of the product can be guaranteed; and the method is suitable for an expanded commercial market. The invention also provides a method for preparing the Oritavancin intermediate A82846B salt and a method for synthesizing Oritavancin by the use of the A82846B salt.

The invention discloses a method for simultaneously detecting various glycopeptides antibiotics in animal derived food. The method mainly comprises the following steps: carrying out solution extraction on a sample; carrying out series purification and enrichment by using HLB solid-phase extraction columns and strong cation (MCX) solid-phase extraction columns; separating the sample by using reversed phase columns, and then detecting the sample by using an ultra-efficient liquid chromatography tandem mass spectrometry in a multi-reaction monitoring mode; and carrying out qualitative and quantitative analysis. Five glycopeptides antibiotics including telavancin, teicoplanin, oritavancin, dalbavancin and vancomycin in the sample animal derived food such as milk, eggs and chicken can be detected simultaneously. The detecting method is sensitive, accurate and rapid; and the five glycopeptides antibiotics can be qualitatively and quantitatively analyzed by six minutes displayed on an instrument. Moreover, the detecting method also has certain reference value for detection of other glycopeptides antibiotics.

The invention discloses a fermentation medium and a production process for producing an oritavancin precursor A82846B. The fermentation medium is used for producing the oritavancin precursor A82846B,and the fermentation medium consists of an organic carbon source, an organic nitrogen source, mineral substances and water, wherein the organic carbon source includes 5-10% of glucose in terms of themass percentage of the fermentation medium, and the organic nitrogen source includes 0.3-1.0% of yeast powder in terms of the mass percentage of the fermentation medium. With the application of the fermentation medium provided by the invention, the yield of the A82846B is greatly improved, and the proportions of two impurities, namely A82846A and A82846C, are obviously reduced. The production process for producing the oritavancin precursor A82846B provided by the invention can effectively improve the yield of the A82846B and reduce the content of the impurities; the production process is applicable to production by virtue of fermenters; and efficient production of the oritavancin precursor A82846B can be achieved.

The invention discloses an improved method for preparing oritavancin. The method takes A82846B acetate as a raw material, under existence of a Brettphos catalyst, a Brettphos ligand, alkali and a solvent, the material and an amino alkylation reagent are subjected to a reaction to generate oritavancin with one step. According to the invention, reaction steps are simplified, the selectivity of amino alkylation is increased, oritavancin yield is increased, and a route suitable for large industrial production is provided.

Glycopeptide antibiotics, such as oritavancin, demonstrate significant activity against B. anthracis. Methods for the treatment, prophylaxis and prevention of B. anthracis infection and disease in animals, including humans, are described.

The invention relates to a medicinal composition for treating complex infection and a preparation method thereof. The medicinal composition is characterized by comprising an active ingredient selected from one of glycopeptides antibacterial drugs of telavancin, dalbavancin, oritavancin, vancomycin, teicoplanin or a pharmaceutically acceptable salt thereof, and also comprising polyene and echinocandin type antifungal agents, and being prepared into a freeze-dried powder injection by adopting a conventional process. The medicinal composition provided by the invention realizes combined application of the antibacterial drugs and the antifungal agents, can simultaneously give play to an antibacterial infection effect and an antifungal infection effect, and is convenient for clinical use.

The invention discloses a group of glycopeptides compounds with anti-resistance bacterial activity. The glycopeptides compounds in accordance with a general formula (I) are as shown in the following specification. The invention further provides a preparation method and an application for the above glycopeptides compounds. Through testing, compared with a second-generation glycopeptides pharmaceutical oritavancin, the glycopeptides antibiotic compounds have the higher inhibitory activity to endurance strains, especially MRSA or VRE. Through further testing, the most of the glycopeptides compounds have the higher safety than the oritavancin, and can be used for preparing pharmaceuticals for treating or preventing various diseases, such as skin and soft tissue infection, cephalomeningitis, sepsis, pneumonia, arthritis, peritonitis, bronchitis, and empyema, caused by bacterial infection.

Glycopeptide antibiotics, such as oritavancin, demonstrate significant activity against both a vegetative form of C. difficile and C. difficile spores. Methods for the treatment, prophylaxis and prevention of C. difficile infection and disease in animals, including humans, are described.

The invention discloses kibdelosporangium aridum and a preparation method of an oritavancin intermediate. The kibdelosporangium aridum strain HS807-AN-2396 with high yield of the oritavancin intermediate is preserved in the China General Microbiological Culture Collection Center (CGMCC), and is assigned with the accession number of CGMCC No.10576. The preparation method of the oritavancin intermediate comprises the following step: fermenting the kibdelosporangium aridum CGMCC No.10576 in a fermentation medium, thus obtaining the oritavancin intermediate A82846B from the fermentation broth. With the adoption of the preparation method, the high yield, namely, 2315mg / L of the fermentation potency of the oritavancin intermediate can be realized on a 60m<3> tank, and thus the industrial production of oritavancin is facilitated.

Disclosed herein are antibacterial compositions, pharmaceutical compositions, and the use and preparation thereof. Some embodiments relate to compositions including oritavancin and their use as therapeutic agents.

The present invention belongs to the technical field of medicine, and particularly relates to an oritavancin compound and a preparation method thereof. The oritavancin compound of the present invention has advantages of high purity, good stability, and not significant moisture absorption weight increase under a high humidity condition.

Methods for the treatment and prevention of bacterial skin infections using the glycopeptide antibiotic oritavancin are disclosed.

The invention relates to a fermentation medium for producing A82846B and a production method of the A82846B, and belongs to the technical field of biology. The invention provides a fermentation culture medium for producing A82846B. The fermentation culture medium contains 20-60 g / L of an organic carbon source, 10-23 g / L of an organic nitrogen source, 6.5-10.5 g / L of inorganic salt, 0.05-1 g / L of vitamin B1 and 0.05-10 g / L of lysine. The invention also provides a production method of the A82846B, and the production method comprises the following steps: inoculating the fermentation culture medium with the Kibdelosporidium aridum, carrying out fermentation culture, and collecting the produced A82846B. According to the method disclosed by the invention, the fermentation titer is remarkably improved, the high yield of 60-80 small aging titer of 4206mg / L in a 6000 L fermentation tank is realized, the yield is far higher than that reported in the existing literature, the fermentation culture time is short, and the method is extremely beneficial to industrial production of oritavancin.

The invention provides an oritavancin purification method. The oritavancin purification method includes the following steps: step (1), dissolving crude oritavancin in an aqueous solution of acetonitrile, performing column chromatography by a polymer microsphere chromatography column, and collecting a chromatographic solution having the oritavancin content higher than 98.5%; step (2), removing solvents from the collected chromatographic solution, and performing concentration to obtain an oritavancin concentrate; step (3), performing filtering and freeze-drying to obtain oritavancin powder. Theoritavancin purification method has the advantages that high-purity oritavancin is obtained through polymer microsphere chromatography, and accordingly, the content of impurities is greatly reduced; the content of the oritavancin can reach more than 98.5% through one-step chromatography, and the method is simple; phosphate and methanol / ethanol / acetonitrile serve as mobile phases for chromatography, later treatment and solvent recovery are facilitated, concentration can be conducted through nanofiltration membranes, and the method is convenient to operate; the purification method improves the product quality and is suitable for expanded commercial production.

Methods of treating bacterial infections in a subject using a synergistic combination of oritavancin and a polymyxin are disclosed.

The invention discloses a producing strain of an oritavancin intermediate (A82846B) and application of the producing strain. The producing strain kibdelosporangium aridum JH100-32B16B of the oritavancin intermediate is preserved in China General Microbiological Culture Collection Center (CGMCC), and the preservation number is CGMCC No.17931. The fermentation method is a method for producing the oritavancin intermediate by fermenting the kibdelosporangium aridum CGMCC No.17931 in a fermentation culture medium. By adopting the producing strain and a corresponding fermentation process thereof, the fermentation titer of A82846B can be 1450mg / L on a 30L fermentation tank by adopting a fermentation culture medium with a low-cost formula, and the fermentation cost is reduced by more than 90% compared with that of a contrast process; and the "impurity-product ratio" (A / B ratio) is as low as 1.5-2.0, and is reduced by more than half compared with a control level, thereby being beneficial to simplifying a product extraction process and reducing the extraction cost. The advantages in two aspects are combined, so that the comprehensive production cost of the A82846B is obviously lower than a control process level reported in the existing literature.

Glycopeptide antibiotics, such as oritavancin, demonstrate significant activity against both a vegetative form of C. difficile and C. difficile spores. Methods for the treatment, prophylaxis and prevention of C. difficile infection and disease in animals, including humans, are described.

Methods of treating bacterial infections in a subject using a synergistic combination of oritavancin and a polymyxin are disclosed.

The invention provides an application of oritavancin phosphate in the preparation of a drug for preventing and treating bovine infectious rhinotracheitis. Oritavancin phosphate can inhibit and kill bovine infectious rhinotracheitis in an in vitro MDBK cell model The virus can effectively inhibit the invasion and replication of bovine infectious rhinotracheitis virus, and has low cytotoxicity. It also lays the foundation for the development of highly effective and specific anti-bovine infectious rhinotracheitis virus drugs and provides a new perspective.

The invention discloses a method for preparing oritavancin by means of carboxyl protecting. The method comprises the steps that carboxyl of A82846B is protected, then the A82846B and 4'-chlorobiphenyl-4-carbaldehyde are subjected to aldehyde-amine condensation, then a C=N bond is reduced, and finally, a carboxyl protecting group is removed to obtain the oritavancin. By means of the method for preparing the oritavancin by means of carboxyl protecting, limitation of the prior art is broken through, in an oritavancin synthesis process, operation of protecting the carboxyl of the A82846B and subsequent synthesis operation of conducting aldehyde-amine condensation on the A82846B and the 4'-chlorobiphenyl-4-carbaldehyde and the like are added, accidentally, the reaction selectivity is improved,not only is the final yield of the oritavancin not reduced, but also the efficiency of subsequent reaction is effectively improved, by-products are reduced, and the yield and the purity of the oritavancin are improved, so that the method has the unexpected effects.

The invention discloses a method for preparing oritavancin. The present invention breaks through the limitations of the prior art. In the synthesis process of oritavancin, the amine group at a specific site is first protected, and the synthesis operation steps are increased, and then subsequent synthesis operations are performed, which not only does not reduce the final product efficiency, while effectively improving the efficiency of subsequent reactions, reducing the generation of by-products, but improving the yield and purity of oritavancin.

The invention provides a pharmaceutical composition capable of resisting chronic infection and biofilm bacteria, the active ingredients of which include clinfloxacin and at least one antibiotic selected from daptomycin and oritavancin; The active ingredient of the composition also includes an additional antibiotic, and the additional antibiotic is at least one antibiotic selected from vancomycin and meropenem. By using the pharmaceutical composition of the present invention, persistent bacteria can be completely eliminated in vitro, and persistent biofilm infection can be effectively eliminated, the lesion can be cured, and inflammation can be relieved; in addition, the pharmaceutical composition of the present invention is suitable for infections in vivo, in vitro, and on the body surface Treatment has a wide range of applications.

The invention provides a method for preparing the high-purity oritavancin key intermediate A82846B, specifically by separating the oritavancin key intermediate A82846B from the fermentation broth, first adjusting the pH, and then purifying the oritavancin key intermediate through a macroporous adsorption resin , then purified by reverse phase chromatography, and finally crystallized to obtain high-purity A82846B. The method adopted in the present invention is simple to operate, uses less organic solvents, and greatly reduces the generation of waste liquid; and overcomes the defects of low adsorption efficiency of cationic macroporous adsorption resins in the prior art and reduced product yield due to leakage adsorption, and is suitable for Industrial production.

Glycopeptide antibiotics, such as oritavancin, demonstrate significant activity against B. anthracis. Methods for the treatment, prophylaxis and prevention of B. anthracis infection and disease in animals, including humans, are described.

The invention discloses an alkaline degradation liquid for preparing oritavancin intermediate A82846B by fermentation. The impurity waste liquid is subjected to alkali degradation to obtain an alkali degradation liquid. After the alkali degradation liquid was added to the fermentation medium, the fermentation was carried out again. By adding different concentrations of impurity alkali degradation liquid, the fermentation unit of A82846B was greatly increased, and the components were significantly improved.

The invention discloses a method for constructing high-yield engineering bacteria of an oritavancin precursor cloireomycin. A high-yield chassis strain capable of being used for efficiently synthesizing glycopeptide antibiotics is constructed by knocking out an NRPS gene responsible for ristomycin biosynthesis in TNS106, inserting an integration site and then inserting a pJLL10 plasmid with a double-copy bbr gene. A bacterial artificial chromosome (BAC) plasmid containing a glycopeptide antibiotic biosynthetic gene cluster is introduced into the high-yield chassis strain to obtain the glycopeptide antibiotic high-yield engineering strain. The shake flask fermentation yield of the cloirusin high-producing strain obtained by the method disclosed by the invention can reach 1440mg / L, and the cloirusin high-producing strain is the strain with the highest shake flask fermentation yield in a public report.

The invention discloses an improved method for preparing oritavancin. The method takes A82846B acetate as a raw material, under existence of a Brettphos catalyst, a Brettphos ligand, alkali and a solvent, the material and an amino alkylation reagent are subjected to a reaction to generate oritavancin with one step. According to the invention, reaction steps are simplified, the selectivity of amino alkylation is increased, oritavancin yield is increased, and a route suitable for large industrial production is provided.