67 results about "Daptomycin" patented technology

The present disclosure provides daptomycin formulations which have improved chemical stability, faster reconstitution times when reconstituted from the solid state and longer in-use stability. The compositions comprise daptomycin, one basic amino acid or its salt and optionally one or more pH adjusting agents.

The present invention relates to compositions comprising daptomycin and at least one amino acid, methods of providing such compositions and the uses thereof.

The present invention provides a high-stability daptomycin composition for injection and preparation method therefor and use thereof. The daptomycin composition for injection comprises daptomycin and a pharmaceutically acceptable carrier, and the pharmaceutically acceptable carrier contains a divalent metal salt, a pH regulator, and an osmotic pressure regulator; and the molar ratio of daptomycin to divalent metal salt in the daptomycin composition for injection is 1:1.0 to 1:3.5. The daptomycin composition for injection of the present invention significantly improves the stability of the preparation, facilitates the storage and transportation of the preparation at room temperature, and ensures the safety of drug use; And the preparation method of the present invention has advantages such as green environmental protection, suitability for industrialization.

The application belongs to the technical field of biological medicine, and particularly relates to a biomimetic nano delivery system based on MRSA outer vesicle coating and application thereof. The application first couples chitosan oligosaccharide and monocarboxylated curcumin through an amide reaction to synthesize an amphiphilic polymer carrier, then loads vancomycin, daptomycin and other drugs through self-assembly to obtain a drug micelle, and finally coats the drug micelle with MRSA outer vesicle to successfully prepare a targeted biomimetic nano delivery system. The prepared biomimetic nano delivery system has excellent antibacterial effect, can realize targeted delivery and long-acting release of antibacterial drugs at an infection site, and is expected to overcome the bottleneck of drug resistance and insufficient drug penetration in traditional treatment, and provides a potential solution for the treatment of diseases such as periprosthetic infection.

The present invention provides an aryliminothiazole compound represented by Formula I or a pharmaceutically acceptable salt thereof, as well as a preparation method and use thereof. These compounds or pharmaceutically acceptable salts thereof can simultaneously enhance the activity of polymyxin E against Gram-negative bacteria and daptomycin against Gram-positive bacteria, and can be used in the antibacterial treatment of pathogens that are insensitive to polymyxins. #imgabs0#

The invention provides a lipopeptide-containing fat dissolving product as well as a preparation method and application thereof, and relates to the field of medical cosmetology. According to the invention, the lipopeptide is applied to the preparation of the fat-dissolving medicine for the first time, and the lipopeptide can be selected from one or more of surfactin, iturin, interleukin, abrumogen, daptomycin, polymyxin, bacitramycin L, phospholipid rhzomorph and bacitramycin D. According to the invention, the lipopeptide is directly injected into the subcutaneous adipose tissue for the first time, so that the accumulation of the local adipose tissue is reduced, and a new active ingredient is provided for the fat dissolving needle; the invention also proves that compared with sodium deoxycholate, the lipopeptide has higher fat-dissolving activity and lower effective dose when being used as a fat-dissolving component; lipopeptide is adopted as a new effective component of the fat-dissolving needle, so that the fat-dissolving needle is safer and more effective, the rupture of an injection part can be reduced, the fat-dissolving needle better fits the pH value of a human body, and the pain in the injection process is reduced.

The invention belongs to the technical field of biological medicine, and particularly relates to a bionic nanometer delivery system based on MRSA outer vesicle coating and application of the bionic nanometer delivery system. Chitosan oligosaccharide and monocarboxylated curcumin are coupled through an amide reaction to synthesize an amphiphilic polymer carrier, then drugs such as vancomycin and daptomycin are entrapped through self-assembly to obtain drug micelles, and finally the drug micelles are coated with MRSA outer vesicles to successfully prepare the targeted bionic nano delivery system. The bionic nano delivery system prepared by the invention has an excellent antibacterial effect, can realize targeted delivery and long-acting release of an antibacterial drug at an infected part, is expected to overcome the bottlenecks of drug resistance and insufficient drug permeation in traditional treatment, and provides a potential solution for treatment of diseases such as periprosthetic infection and the like.

The present invention relates to the use of apabicin in a method for treating bacterial infections associated with biofilms containing Staphylococcus bacteria, wherein the method comprises administering apabicin in combination with daptomycin and / or one or more additional agents selected from lipopeptides, glycopeptides, and lincosamides, or vancomycin to the patient.

The invention relates to the technical field of medicine synthesis, in particular to a daptomycin production method which comprises the following steps: conducting a daptomycin crude product by using a nanofiltration membrane, and performing nanofiltration concentration to obtain a nanofiltration concentrated solution; loading the obtained column loading liquid on NMQ-K resin, washing with water, carrying out gradient elution with a sodium chloride solution, and collecting an effective daptomycin production intermediate collection liquid with the purity of more than 75%; and concentrating by using a nanofiltration membrane until the unit of feed liquid is 50,000-160,000, so as to obtain a purified daptomycin product. The method disclosed by the invention has the beneficial effects that daptomycin is combined with NMQ-K ion exchange resin for adsorption by utilizing the characteristic that daptomycin contains quaternary amine groups, then gradient analysis is performed through a salt solution, and the part meeting the requirements is collected. The yield can be improved, and the production requirement can be met. By using the process disclosed by the invention, a daptomycin product meeting the requirement can be obtained, the sample loading amount is increased to several times of the original sample loading amount, and the impurity removal rate is also increased while the productivity is improved.

Naphthoquinone derivatives of Lawsone have been found to be effective against Staphylococcus aureus and methicillin resistant Staphylococcus aureus (MRSA). Such compounds generally contain a substituent group at the 3-position of a specific naphthoquinone compound, i.e. 2-hydroxy-1,4-naphthoquinone. One of these derivatives referred to as compound 6c in the series exhibits potent antimicrobial activity that is comparable to that of the two commercial antibiotics ofloxacin and ciprofloxacin against the two strains of methicillin sensitive Staphylococcus aureus (MSSA; ATCC 29213 and ATCC 6538). In the case of two strains of MRSA (ATCC BAA-44 and ATCC BAA-1717) that have developed drug resistance to both ofloxacin and ciprofloxacin, the antimicrobial activity of 6c can almost rival that of vancomycin and daptomycin. Furthermore, 6c is also effective against vancomycin-intermediate and daptomycin non-susceptible strain of MRSA (ATCC 700699). Besides the efficacy, 6c has a much improved drug resistance profile in comparison with the conventional antibiotics.

The invention provides inter alia an aqueous solution composition of pH in the range 6.0 to 8.0 comprising: —daptomycin or an analogue thereof, or a salt thereof; —a divalent metal cation; and —one or more salts which are not divalent metal cation salts or amino acid salts or buffer salts at a total concentration of 300 mM or more.

The present invention belongs to the field of biological medicine technology, and relates to a new application of daptomycin, specifically the application of daptomycin in the preparation of drugs for treating or preventing chronic pancreatitis. Daptomycin can inhibit macrophage M2 polarization, reduce pancreatic fibrosis caused by chronic pancreatitis, and reduce pancreatic tissue changes caused by chronic pancreatitis. The present invention may provide an effective prodrug for the prevention and treatment of chronic pancreatitis.

The present invention relates to the field of pharmaceutical technology, and in particular, to a daptomycin nano-FORMULATION, a method for preparing same, and use thereof. The method comprises: A, encapsulating daptomycin with a copolymer poly(lactic-co-glycolic acid) to give a nanoparticle (NP); and B, sonicating a cell membrane vesicle overexpressing RANK and the nanoparticle (NP) in a water bath for 3 min, and then sequentially extruding the mixture through polycarbonate membranes of 800 nm, 400 nm, and 200 nm to give the daptomycin nano-formulation. The weight ratio of the membrane protein to PLGA is 0.25. By the method of the present invention, a daptomycin nano-formulation targeting rheumatoid arthritis is successfully prepared. The daptomycin nano-formulation prepared by the present invention has good stability. The daptomycin nano-formulation of the present invention has good therapeutic effects against RA.

The present disclosure relates to a solid formulation of daptomycin comprising at least one branched aliphatic amino acid. Solid daptomycin formulation of the present disclosure shows improved reconstituted time. The disclosure further relates to a method of preparation of the solid daptomycin formulation according to this disclosure.

The application belongs to the technical field of biological medicine, and particularly relates to application of pantothenic acid or a pharmaceutically acceptable salt thereof in preparation of a medicine for enhancing sensitivity of pathogenic bacteria to daptomycin. It is found for the first time that addition of pantothenic acid or a pharmaceutically acceptable salt thereof can improve the sensitivity of gram-positive bacteria including Staphylococcus aureus, Streptococcus agalactiae and Corynebacterium diphtheriae to daptomycin, significantly improve the bactericidal effect, and further research shows that pantothenic acid or a pharmaceutically acceptable salt thereof can promote the clearance, formation and reduction of pathogenic bacteria biofilm by daptomycin. The finding opens up a new way for overcoming antibiotic resistance and optimizing anti-infection treatment strategies.

The invention relates to the field of daptomycin production, in particular to a drying method of daptomycin. According to the method, firstly, an evacuation channel in a daptomycin crystal is opened by adopting an ultrasonic vacuum drying method, and a solvent contained in a crystal solid is quickly volatilized under a vacuum drying condition, so that the vacuum drying efficiency is improved. The method has the advantages that the raw materials are recycled, then the nitrogen is introduced for boiling drying, the drying process is carried out under the oxygen isolation condition, moisture can be quickly dried, impurity growth can be effectively controlled, and the method is low in energy consumption, high in efficiency and high in industrial implementation performance.

A preparation method for a stable crystal form of daptomycin, comprising the following steps: (1) dissolving a daptomycin raw material in water and mixing evenly to obtain a daptomycin aqueous solutio

The present invention relates to the use of Afabicin in a method of treating bacterial infections involving biofilm that contains staphylococcus bacteria, wherein the method comprises administering Afabicin in combination with at least one further agent selected from lipopeptides, glycopeptides and lincosamides, such as Daptomycin and / or Vancomycin to the patient.

The present invention discloses an adenylated protein A8 mutant, its coding gene, and its application as a key enzyme of the adenylation domain in a structural analog of daptomycin substituted with Gly<supgt;8< / supgt>. The adenylated protein A8 mutant is obtained by point mutation of the 277th amino acid of the adenylated protein A8 with the amino acid sequence shown in SEQ ID NO.1. By means of genetic engineering and enzyme engineering, the present invention studies the active site of the A domain, and determines the key amino acid residue (the 277th residue of A8) related to the substrate specificity of the A domain through constructing mutants, providing a new way for the structural expansion of daptomycin family compounds. Compared with the adenylated protein A8, the obtained mutant Y277P has an altered substrate specificity, with a significantly reduced activity towards L-Ala and a significantly increased activity towards L-Gly, providing a new way for obtaining a structural analog of daptomycin substituted with Gly<supgt;8< / supgt>.

Embodiments of the present disclosure generally relate to a new class of daptide antibiotics and compositions that include the daptide antibiotics. Embodiments described herein also generally relate to methods of treating various diseases or medical conditions in a patient utilizing the new class of daptide antibiotics and compositions thereof. In an embodiment, a composition for treating a skin condition in a patient is provided. The composition includes a daptide comprising: a dimethylated 7V-terminus; a Dmp-modified C- terminus; a dehydrobutyrine residue positioned between the dimethylated 7V-terminus and the Dmp-modified C-terminus; at least one alanine (A) residue or at least one dehydroalanine (Dha) residue positioned between the dimethylated 7V-terminus and the Dmp-modified C- terminus; and at least one amino acid residue positioned between the dimethylated 7V-terminus and the Dmp-modified C-terminus. In another embodiment is provided a daptide bacteriocin composition that is antimicrobial against a staphylococcal skin bacteria in a patient.

The invention relates to a daptomycin staphylococcus aureus heterogeneity drug resistance identification method based on machine learning, which comprises the following steps: S1, preparing and downloading modeling data, collecting sensitive, drug-resistant and heterogeneity drug-resistant data of staphylococcus aureus to daptomycin, obtaining sequencing data, screening laboratory strains, and screening the screened strains to obtain a sample; determining the heterogeneity drug-resistant phenotype and then sending the heterogeneity drug-resistant phenotype to be used as data for model construction and model evaluation; s2, data preprocessing is carried out, after the data sent to be tested are obtained, a series of operations of filtering, splicing, evaluating and Kmer segmentation need to be carried out on the data, and a data matrix for model construction is obtained; s3, performing model construction and parameter adjustment; and S4, performing new data processing and model prediction. According to the method, time and labor cost can be greatly reduced through machine learning prediction, meanwhile, a large amount of data can be effectively predicted, and the heterogeneity drug-resistant phenotype of a clinical strain can be rapidly diagnosed through a model prediction method.

To provide a solid pharmaceutically acceptable formulation of daptomycin having an improved reconstitution time.SOLUTION: This solid formulation comprises daptomycin, arginine, histidine, and at least one branched aliphatic amino acid selected from the group consisting of leucine, isoleucine, valine, and pharmaceutically acceptable salts thereof. In the solid formulation, the molar ratio of the at least one branched aliphatic amino acid to daptomycin is from 0.5:1 to 5:1.SELECTED DRAWING: None

The invention belongs to the technical field of biological medicines, and particularly relates to application of daptomycin in preparation of a non-small cell lung cancer KRAS G12C inhibitor drug resistance reversal agent. It is found that the problem of drug resistance of non-small cell lung cancer to a KRAS inhibitor can be solved through combination of daptomycin and adagraxib, an excellent anti-tumor effect is shown, the drug resistance phenotype mediated by an acquired drug resistance mechanism can be remarkably reversed, no obvious toxic or side effect is observed in an experimental animal body, and the safety characteristic is good. In order to overcome the problem of drug resistance of targeted drugs such as KRAS inhibitors, the invention provides a novel combined treatment solution with high efficiency and safety.

This invention belongs to the field of biomedicine, and specifically relates to a purification method for daptomycin. The purification method includes loading a sample solution onto a C18 resin chromatography column equilibrated with an equilibration buffer, and eluting the C18 resin chromatography column with an eluent; wherein the sample solution, the equilibration buffer, and the eluent contain a sodium salt at a concentration of 0.1–1.0 (w / v)%, and the pH of the sample solution, the equilibration buffer, and the eluent is 6–8; the ethanol content of the sample solution, the equilibration buffer, and the eluent is 5–40%; and the sodium salt is selected from sodium sulfate, sodium phosphate, and sodium chloride. The purification method provided by this invention can achieve efficient removal of impurity 4 and unknown impurities from daptomycin, and the obtained product meets market demand.

The application belongs to the technical field of separation and crystallization, and relates to a preparation method of a stable crystal form of daptomycin. Daptomycin raw materials are dissolved in water and mixed to obtain a daptomycin aqueous solution, acetic acid buffer is added to the daptomycin aqueous solution and mixed to obtain a mixed solution, the mixed solution is vacuum concentrated to obtain a concentrated solution, the concentrated solution is heated and dissolved to obtain a saturated solution system, the saturated solution system is cooled, and after solid is precipitated, stirring is performed at the current crystallization temperature to crystallize; after the crystallization is completed, the system is continuously cooled to obtain a crystallization mother liquor containing daptomycin crystals; finally, the daptomycin crystals are washed at low temperature, daptomycin crystal crude products are collected by centrifugation, and the crude products are dried to obtain daptomycin crystals. The order of the daptomycin crystals prepared by the method is obviously better than that of the daptomycin crystals prepared by the crystallization method reported in the prior art.

The invention discloses a preparation method of a high-purity daptomycin finished product. The method comprises the following steps: firstly, pre-treating and flocculating daptomycin fermentation liquor, and then filtering; separating and purifying the filtrate through macroporous resin adsorption and desorption and ion exchange resin adsorption and desorption, then carrying out nanofiltration concentration, and then carrying out crystallization, suction filtration and drying to obtain a daptomycin crystal crude product; and dissolving the crystallized crude product with purified water, desalting on a column, and separating and purifying through a C18 filler high-pressure preparative column. By using the method, the daptomycin with the purity higher than 98% can be separated and purified from the daptomycin fermentation liquor; the method is simple and convenient in process flow, high in purification and crystallization process purity, high in yield, short in period and strong in operability; solvent materials are low in consumption and non-toxic; the production and operation cost is relatively low, and the obtained product is relatively high in purity and stable in yield; and the method has a good medical industrial enlarged application prospect.

The present disclosure provides daptomycin formulations which have improved chemical stability, faster reconstitution times when reconstituted from the solid state and longer in-use stability. The compositions comprise daptomycin, one basic amino acid or its salt and optionally one or more pH adjusting agents.

The invention belongs to the technical field of biological medicine, and particularly relates to application of pantothenic acid or pharmaceutically acceptable salt thereof in preparation of a medicine for enhancing sensitivity of pathogenic bacteria to daptomycin. It is found for the first time that by adding pantothenic acid or pharmaceutically acceptable salt thereof, the sensitivity of gram-positive bacteria including staphylococcus aureus, streptococcus agalactiae and corynebacterium diphtheriae to daptomycin can be improved, and the sterilization effect is remarkably improved; further researches show that pantothenic acid or pharmaceutically acceptable salts thereof can promote removal of pathogenic bacteria biofilms by daptomycin, and form and reduce drug resistance of pathogenic bacteria to daptomycin. The discovery opens up a new way for overcoming the problem of antibiotic resistance and optimizing an anti-infection treatment strategy.

The present invention relates to a synthetic promoter operably linked to a daptomycin biosynthetic gene cluster; a gene construct for producing daptomycin in which the synthetic promoter and a daptomycin biosynthetic gene cluster are operably linked; a recombinant expression vector for producing daptomycin containing the genetic construct; and a transformant for producing daptomycin that has been transformed with the recombinant expression vector, wherein the synthetic promoter can increase the transcriptional activity of the daptomycin biosynthetic gene cluster, and the transformant that has been transformed with the recombinant expression vector containing the synthetic promoter and the daptomycin biosynthetic gene cluster can be effectively used in the field of medicine and pharmacy by enabling mass production of daptomycin.

The invention belongs to the technical field of biological medicines, and particularly relates to application of daptomycin in preparation of a non-small cell lung cancer EGFR-TKI drug resistance reversal agent. The invention discloses that daptomycin can effectively reverse drug resistance for the first time: in-vitro experiments show that evaluation is performed by adopting an HSA model of SynergyFinder software, and it is found that the drug combination synergy score of daptomycin and osimertinib in H1975 drug-resistant cells is 18.166, which indicates that daptomycin and osimertinib have a strong synergistic effect, and the drug resistance of daptomycin and osimertinib can be effectively reversed. Cloning formation experiments show that the cell proliferation inhibition rate of a drug combination group is increased by more than 80% compared with that of a single drug group, and a strong synergistic effect is achieved. An in-vivo experiment further verifies that the tumor volume of a combined drug group is reduced by about 80% compared with that of an osimertinib single drug group, the tumor weight is obviously reduced, drug-resistant relapse does not occur in a treatment period of 22 days, and meanwhile, the stability of the weight of a mouse shows that the safety is good. The invention provides a combined treatment scheme with high efficiency and safety for overcoming EGFR-TKI drug resistance, and has important clinical transformation value.