68results about "Polymyxins" patented technology

The invention belongs to the technical field of gene engineering, and particularly relates to a mutant of polymyxin efflux transporter and application of the mutant. The mutant is a PmxD transporter mutant, the amino acid sequence of the PmxD transporter mutant is shown as SEQ ID NO: 1, and compared with wild type PmxD, the polymyxin transport capacity of the PmxD transporter mutant (T38W) is improved by 450.46%; and the total discharge amount of polymyxin is increased by 85.72%. Meanwhile, the mutant can significantly improve the growth ability of the strain on a plate containing 250 [mu] g / mL of polymyxin B, namely significantly improve the autoresistance of paenibacillus polymyxa to polymyxin.

The invention belongs to the field of biology, and discloses a polymyxin B specific degrading enzyme and application thereof. The amino acid sequence of the polymyxin B specific degrading enzyme is as shown in SEQ ID NO: 1. The polymyxin B specific degrading enzyme disclosed by some embodiments of the invention can selectively degrade polymyxin B1-1 and polymyxin B3, and does not influence the activity of polymyxin B1 and polymyxin B2, so that the polymyxin B specific degrading enzyme can be used for purification in the preparation process of polymyxin B; the polymyxin can resist acid, alkali and organic solvents, and can efficiently identify and decompose polymyxin B1-1 and B3 components under various conditions. The porous microspheres are used as the solid-phase carrier, so that the surface of the microspheres can accommodate more enzyme ligands, the acid-base resistance and organic solvent resistance of the ligands can be effectively improved, and the polymyxin B purification efficiency can be effectively improved.

The invention provides novel pharmaceutical compositions of polymyxin B / trimethoprim and rifampin, as well as methods of their preparation and topical ophthalmic uses (e.g., treatment of ophthalmic infections).

A polyclonal antibody composition specifically binds the pTonB epitope (SEQ ID NO: 11) from Acinetobacter baumannii and is elicited by immunization with a multi-epitope antigen comprising thioredoxin leader, rigid linker, and kernels including SEQ ID NOs: 6, 7, 11, 12, and 8. These antibodies enhance opsonophagocytic killing of A. baumannii Ci79 via classical complement activation and Fey receptor-mediated phagocytosis by bone marrow-derived macrophages. Absorption of pTonB-specific antibodies reduces killing by >70%, confirming epitope dominance. Passive transfer of the composition protects >60% of mice in a lethal intranasal challenge model. Pharmaceutical compositions, treatment methods (alone or with antibiotics like colistin), prophylactic uses, diagnostic kits, and polyclonal compositions are disclosed for combating multidrug-resistant A. baumannii infections.

The invention provides a preparation method of impurities B1, B2, B3 and B1-1 in polymyxin sulfate B. The method comprises the following steps: preparing raw materials: taking polymyxin sulfate B as a raw material, using 30-50m C18 as a filler, acetonitrile, dipotassium hydrogen phosphate, ammonia water, anhydrous sodium sulfate, phosphoric acid and trifluoroacetic acid as analytically pure materials, using deionized water, and using a nylon column as a column; conducting analytical purification: weighing raw materials and adding fillers into the column, loading the sample, and treating the sample with an eluent; conducting concentration and desalting on the analytically purified fraction; conducting concentration and desalting on the fraction in step 3; conducting crystallization: reducing the pressure on the fraction in step 3 to recover the solvent on a rotary evaporator, adding ammonia water to adjust the pH value to precipitate the precipitate, filtering, washing with water, and vacuum drying to obtain the product; and successfully preparing high-purity B1, B2, B3 and B1-1 through a specific process combination of separation and purification, concentration and desalting, crystallization or freeze drying. For example, the purity of B1 product can reach 96.05%, the purity of B3 can reach 91.28%, and the purity of B1-1 can reach 94.83%. These high-purity products, whether used as drug raw materials or scientific research reference substances, can provide a reliable material basis for related research and production, effectively reduce the interference of impurities on experimental and production results, and improve the accuracy of research and the stability of product quality.

The present invention provides therapeutic compounds, such as compounds of formula I, or pharma- ceutically acceptable salts, hydrates or solvates thereof, pharmaceutical compositions thereof, methods of use thereof, and methods for making these compounds, as therapeutic or anti-cancer agents.

The present invention provides methods, compositions, and articles of manufacture useful for the prophylactic and therapeutic amelioration and treatment of gram-positive bacteria, and related conditions. The present invention provides compositions and methods incorporating and utilizing macolacin antibiotics or derivatives or variants thereof.

The invention provides polymyxin B sulfate and a preparation method thereof. According to the method, paenibacillus polymyxa is fermented in a liquid culture medium with wheat flour as a main carbon source and cottonseed cake powder and high-temperature soybean cake powder as main nitrogen sources to generate polymyxin B, and aluminum oxide is used as a chromatography medium to purify polymyxin B sulfate through a column chromatography process. Wheat peptone is added into the seed tank, so that growth of hyphae is facilitated, and the hyphae are full; the inoculation amount is reduced, and the seed expanding period is shortened. In the middle stage of fermentation, the amino acid mixed liquid is supplemented, so that the yield of the polymyxin B is increased, and specific impurities after the component B2 can be reduced. The quality of the product prepared by the method is obviously improved, the preparation method does not use an organic solvent and is green and environment-friendly, aluminum oxide can be regenerated and reused, and industrial production is facilitated.

Compositions and methods are provided for treating bacterial infections, including those that are challenging to treat by conventional medications, such as hospital acquired bacterial pneumonia (HABP), ventilator associated bacterial pneumonia (VABP), and bacteremia, caused by carbapenem-resistant bacteria such as Acinetobacter baumannii and Pseudomonas aeruginosa.

The application discloses a decapeptide derivative, a preparation method and application thereof. The application protects a Paenibacillus polymyxa, that is, Paenibacillus polymyxa CPCC 101223, and the preservation registration number is CGMCC No. 22854. The application also protects a preparation method of the compound, which comprises the following steps: fermenting and culturing the Paenibacillus polymyxa CPCC 101223 to obtain the compound. The application also protects application of the compound or a pharmaceutically acceptable salt thereof in preparation of a bacterial inhibitor. The application also protects the bacterial inhibitor, which contains the compound or the pharmaceutically acceptable salt thereof. The compound of the application is derived from the Paenibacillus polymyxa, has a simple preparation process, has good activity against gram-negative drug-resistant bacteria, provides a theoretical basis for clarifying the structure-activity relationship of the decapeptide antibacterial activity, and is suitable for research on a gram-negative drug-resistant bacteria leading compound or preparation of a gram-negative drug-resistant bacteria drug.

The present application provides a polymyxin prodrug compound with the structure shown in formula (I) or a stereoisomer or a pharmaceutically acceptable salt thereof. The polymyxin prodrug compound of the present application can effectively reduce the biological toxicity of polymyxin, selectively activate in bacterial infected tissues, achieve bacterial killing in infected sites, improve the bioavailability of polymyxin, achieve sustainable development and utilization of classic antibiotics, expand the scope of future clinical application of polymyxin, and has a broad clinical application prospect.

The application discloses a preparation method of polymyxin B sulfate impurity Z3 control product, and comprises the following steps: preparing a mobile phase, dissolving a sample containing polymyxin B sulfate, and then loading the sample into a chromatographic column, eluting the sample with the mobile phase, intercepting a fraction between a peak valley position of impurity B1-I and B1, and then re-loading and eluting the fraction to obtain a B1-I, Z3 and B1 triple peak after concentration, collecting a fraction corresponding to a peak part of Z3, repeatedly loading and eluting the fraction after concentration, and finally crystallizing to obtain a product Z3. The application has the advantages of simple operation, good separation effect and high-purity Z3 control product.

A novel 10 peptide capable of inhibiting the growth of bacteria that are resistant to existing polymyxin, a pharmaceutical composition comprising the novel 10 peptide, and an application thereof in the treatment or prevention of bacterial infections.

Colistin is an important last-resort antibiotic, but its production involves significant challenges due to the presence of impurities resulting from various analogs and the limited number of native producers. In response, disclosed are mutant Paenibacillus bacteria that produce Colicin A more efficiently and / or Colicin A that is of higher purity and / or has a cleaner metabolite background. The disclosed mutant bacteria are genetically engineered to inactivate expression of one or more biosynthetic gene clusters (BGCs), increase expression of one or more other BCGs, and / or increase expression of one or more L-DABA pathway genes.

This application discloses a fluorescent probe for labeling the outer membrane of Gram-negative bacteria, its preparation method, and its application. The fluorescent probe uses polymyxin (with its hydrophobic tail and two amino acid residue pairs removed) as a targeting group specifically targeting the outer membrane of Gram-negative bacteria. This structure can specifically bind to the lipopolysaccharide structure in the outer membrane, and is then linked to the fluorophore rhodamine, which has switching properties, to design and synthesize a fluorescent dye. This fluorescent probe, possessing fluorescent switching properties, can be applied to super-resolution imaging of the outer membrane of Gram-negative bacteria.

The invention relates to polymyxin analogues that contain unique lipids anchored by a novel 2-thioethyl ester linkage via the peptide back bone.

This application provides therapeutic compounds, e.g., compounds of formula I, or pharma- ceutically acceptable salts, hydrates or solvates thereof that are therapeutic or anti-cancer agents, pharmaceutical compositions thereof, methods of use thereof, and methods of preparing these compounds.

The application relates to the technical field of coating preparation, in particular to a preparation method of a hydrophilic antibacterial hydrogel coating, which comprises the following steps: after acrylic acid, 4-acryloyloxybenzophenone, a thermal initiator, water and N,N,N',N'-tetramethyl ethylenediamine are mixed and react in the dark, a polymer solution with photo-reaction is obtained; the polymer solution is mixed with a zwitterionic monomer, a crosslinking agent and water to obtain a coating liquid; a substrate is treated with 10wt% 4-acryloyloxybenzophenone organic solvent for 5-10 minutes, the obtained coating liquid is coated on the surface of the substrate, is cured under ultraviolet light, is immersed in water to remove unreacted substances, and a hydrophilic hydrogel coating is obtained; the obtained hydrophilic hydrogel coating is immersed in a 2-(N-morpholine)ethanesulfonic acid (MES) solution containing 0.4M EDC and 0.1M N-hydroxysuccinimide (NHS) to perform activation treatment; colistin sulfate is added into the above MES solution to perform activation treatment, and a hydrophilic antibacterial hydrogel coating is obtained.

The present invention provides a combination antibiotic therapy for treating A. baumannii infections in a subject. The combination therapy includes rifabutin, and members of the polymyxin class of antibiotics such as, for example, commercially available natural product antibiotics such as polymyxin B and polymyxin E (colistin and its prodrug colistin methanesulfonate (CMS)), and synthetic or semi-synthetic derivatives and analogs such as, for example, SPR206, MRX-8, and QPX9003, and polymyxin-like antibiotics such as, for example, Po17306.

The invention provides a polymyxin compound of formula (1) and salts, solvates and protected forms thereof, pharmaceutical compositions comprising the compounds of formula (1), and the use of the compounds and compositions in methods of treatment, such as methods for the treatment of microbial infections. The compounds of formula (1) are represented thus:wherein —R15 is a group:and —R16 is hydrogen; —R17 is hydrogen -L- is a covalent bond or methylene; and —Ar is optionally substituted aryl. The groups —X—, —R1, —R2, —R3, —R4, and —R8 are as defined herein.

The invention provides antibiotic combination therapies for treating an A. baumannii infection in a subject. The combination therapies include rifabutin and a member of the polymyxin class of antibiotics, such as commercially available natural products antibiotics, e.g., polymyxins B and polymyxins E (colistin and its pro-drug colistin methane sulfonate (CMS)) and synthetic or semi-synthetic derivatives and analogs, e.g., SPR206, MRX-8 and QPX9003 and polymyxin-like antibiotics, e.g., Pol7306

The invention relates to the technical field of microbial pharmacy, in particular to a method for improving the fermentation level of polymyxin B by using active peptide BHL. The method comprises the following steps: activating polymyxin B producing bacteria, picking and inoculating the polymyxin B producing bacteria into a seed culture medium containing active peptide BHL, and then placing the seed culture medium in a constant-temperature shake-flask incubator at 27-31 DEG C and 220 rpm for shake culture for 20-24 hours to obtain a seed solution; transferring the seed solution into a fermentation culture medium containing active peptide BHL, and then placing the fermentation culture medium in a constant-temperature shake-flask incubator at 27-31 DEG C and 220 rpm for shaking fermentation culture for 20-65 hours to obtain a fermentation solution; and adjusting the pH value of the fermentation liquor to 1.8-2.5 by using oxalic acid, and then detecting the titer of the polymyxin B.

The present invention provides antimicrobial peptide compounds, pharmaceutical compositions and methods of their use for inhibiting the growth of microorganisms. The present invention also relates to a method for inhibiting the total drug resistance of Acinetobacter baumannii, and a method for inhibiting the total drug resistance of Acinetobacter baumannii by administering the peptide compound to a subject. Provided is a method for the inhibition of fully drug resistant Acinetobacter baumannii using a synergistic combination of the peptide compound acetyl-AS-aib-LRKL-aib-KRLL-amide (SEQ ID NO: 1) and polymyxin B. The invention also provides a method for the inhibition of fully drug resistant Acinetobacter baumannii. In other methods, a peptide compound is provided for the inhibition of Porphyromonas gingivalis (P.gingivalis), which is the key bacterium of the most six most common infectious periodontal disease in the world.

The invention aims to provide a novel polymyxin compound as well as a preparation method and application thereof. The compound provided by the invention is shown as a formula (IV), r1 is (CH3) 2CH or CH3CH2CH (CH3) or CH3CH2CH2, and R2 is CH3CH2CH3 or CH3CH2CH2; and R2 is H or CH. The invention also protects the application of the compound or the pharmaceutically acceptable salt thereof in preparation of a bacterial inhibitor. The invention further provides the paenibacillus polymyxa CPCC 101041 and the application of the paenibacillus polymyxa. The compound is obtained by being separated from a fermentation product of paenibacillus polymyxa CPCC 101041. The invention further discloses a preparation method of the compound. # imgabs0 #

The present invention discloses a cyclopeptide glass and a pharmaceutical composition glass containing a cyclopeptide. The cyclopeptide glass of the present invention can exert both the effect of a drug and the function of a drug adjuvant, and compared with crystals and conventional pharmaceutical dosage forms and adjuvants, it can effectively accelerate the dissolution rate of a drug and improve the bioavailability of a drug, and is widely applied in the fields of drug delivery and sustained release, such as antitumor, antiviral, antibacterial, blood sugar control, immunoregulation, and neuroregulation.

The invention relates to novel compounds with the ability to link an immune response to a pathogen, to the use of said compounds in a disease or disorder mediated and / or caused by an infective agent, to compositions containing said compounds, processes for their preparation and to novel intermediates used in said process.

The invention belongs to the technical field of biological fermentation, and particularly relates to a fermentation medium, a fermentation method and application of polymyxin B sulfate. According to the method, carbon and nitrogen sources for fermentation are optimized, special amino acid is added, fed-batch components are optimized, the fermentation process is controlled, the adjusted fermentation culture medium and fermentation method meet the standards of EP8.0 and CP2015, the fermentation titer is high, the ratio of a fermentation product B1 / B2 is high, the purity of a target product is high, loss caused by follow-up refining or purification is reduced, and industrial popularization is facilitated.

Colistin is an important last-resort antibiotic, but its production involves significant challenges due to the presence of impurities resulting from various analogs and the limited number of native producers. In response, disclosed are mutant Paenibacillus bacteria that produce Colicin A more efficiently and / or Colicin A that is of higher purity and / or has a cleaner metabolite background. The disclosed mutant bacteria are genetically engineered to inactivate expression of one or more biosynthetic gene clusters (BGCs), increase expression of one or more other BCGs, and / or increase expression of one or more L-DABA pathway genes.