60 results about "Multi drug resistant" patented technology

The invention discloses a full D-type antibacterial peptide with high enzymolysis stability and broad-spectrum antibacterial activity and application thereof. The antibacterial peptide is obtained by sequentially and repeatedly arranging D-type tryptophan, D-type arginine and D-type lysine for four times and carrying out C-terminal amidation; the amino acid sequence of the gene is (D-Trp)-(D-Arg)-(D-Lys)-(D-Trp)-(D-Arg)-(D-Lys)-(D-Trp)-(D-Arg)-(D-Lys)-(D-Trp)-(D-Arg)-(D-Lys)-(D-Trp)-(D-Arg)-(D-Lys)-NH2, and is marked as DWRK-12. The antibacterial peptide shows broad-spectrum antibacterial activity and excellent stability, can effectively resist clinically separated multidrug resistant strains, and keeps high cell selectivity at the same time. Due to the characteristics, the antibacterial peptide has important application value in the aspect of developing novel antibacterial drugs, especially in the field of treatment of infection of multiple drug-resistant bacteria.

The invention belongs to the technical field of medicines, and provides a novel method for overcoming multidrug resistance of tumors based on innate immune regulation. The invention relates to an application of an agonist of an innate immune STING pathway and an ENPP1 inhibitor in overcoming multidrug resistance of tumors and enhancing an anti-tumor curative effect. The STING agonist or the ENPP1 inhibitor is combined with an anti-tumor chemical drug for application, so that the effects of overcoming the multi-drug resistance of chemotherapeutic drugs and enhancing the anti-tumor curative effect are achieved. The STING agonist / or ENPP1 inhibitor has the effect of reversing multidrug resistance of tumors, and can enhance the sensitivity of cancer cells to chemotherapeutic drugs and monoclonal antibody drugs, so that the curative effect of antitumor drugs is enhanced, and the STING agonist / or ENPP1 inhibitor is expected to be developed into a novel reversal agent drug for multidrug resistance tumors. The novel anti-multidrug resistance strategy provides a new thought for drug design and cancer treatment, and has a great application prospect in clinical treatment of cancers.

The invention discloses an application of a multidrug-resistant efflux transporter gene OsMRET1 in regulation and control of chalkiness traits of rice. A nucleotide sequence of a coding region of the gene is shown as SEQ ID No.1, and a coded amino acid sequence is shown as SEQ ID No.2. The invention further discloses an application of the multidrug-resistant efflux transporter gene OsMRET1 in regulation and control of chalkiness traits of rice. It is found for the first time that the gene OsMRET1 can regulate and control formation of chalkiness, an OsMRET1 gene knockout mutant is created through a gene editing technology, an OsMRET1 gene overexpression strain is obtained through a transgenic technology, it is verified that the OsMRET1 gene is a new gene for regulating and controlling rice chalkiness, and overexpression of the gene can reduce rice chalkiness and improve rice chalkiness. And a new gene resource and a technical route are provided for rice quality improvement.

The invention belongs to the technical field of polypeptide drugs in biochemistry, and discloses three antibacterial peptide analogues as well as a preparation method and application thereof, the sequence of an antibacterial peptide P-1 is CH3CO-GGGENIKKILSKIKLLK-NH2, the sequence of an antibacterial peptide P-2 is CH3CH2CH2CO-GGGENIKKILSKIKLLK-NH2, the sequence of an antibacterial peptide P-3 is CH3 (CH2) 6CO-GGGENIKKILSKIKLLK-NH2, the carboxyl ends of polypeptides are subjected to amidation, and the polypeptides are all positively charged when the pH is equal to 7. The artificially synthesized antibacterial peptide disclosed by the invention shows a remarkable sterilization effect on multidrug resistant staphylococcus epidermidis. P-1, P-2 and P-3 have small molecular weight, are convenient to synthesize, have broad-spectrum bactericidal activity, are self-assembled into nanoparticles, have low cytotoxicity, resist trypsin degradation and the like, and have wide application prospects.

Compositions comprising 5. salivarius strain SALI-10 and / or salivarius 10 peptide are taught. Also taught are methods of treating bacterial infections comprising administering a pharmaceutically acceptable amount of the composition to the patient with a bacterial infection caused by a pathogen from, for example, multi-drug resistant (MDR) Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus dysagalactiae, vancomycin-resistant Enterococcus faecium, Porphyromonas gingivalis, Tannerella forsythia, and MDR Enterococcus faecalis.

The present invention aims to provide novel compounds and their salts that are effective in the treatment, prevention, and / or diagnosis of seizures in diseases accompanied by epileptic seizures or convulsive seizures. [Solution] Formula I: TIFF2026050464000087.tif2685 [In the formula, each symbol is as described in the specification.] This relates to the pharmaceutical uses of the compounds and salts thereof shown in [reference]. These compounds and salts are useful for the treatment, prevention, and / or diagnosis of seizures in diseases involving epileptic or convulsive seizures (including multidrug-resistant seizures, refractory seizures, acute symptomatic seizures, febrile seizures, and status epilepticus).

The invention discloses an intelligent synergistic administration composition and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations and delivery. The composition takes lipidosome as a carrier, the surface of the lipidosome is modified with a peelable PEG protective layer with'enzyme / pH dual gating 'responsiveness, and the lipidosome is used for being activated under specific conditions of a tumor microenvironment to realize accurate targeting. The interior of the composition is covalently connected with a synergistic auxiliary drug for overcoming multi-drug resistance through chemical bonds sensitive to acid, and a main-effect anti-cancer drug is physically entrapped. After entering the target cell, the auxiliary drug is preferentially and rapidly released in the lysosome by means of the acid-sensitive bond so as to inhibit the drug efflux pump function; and then the main-effect medicine is slowly released, so that programmed sequential administration is realized. Through the collaborative design of intelligent shelling and sequential release, the technical problems of poor targeting property and difficulty in overcoming drug resistance in drug delivery are solved, and the collaborative anti-tumor effect is remarkable.

The present invention relates to a composition for inhibiting multidrug resistance, the composition containing an autocrine motility factor (AMF) as an active ingredient. Specifically, treating cancer cells with an AMF protein or an AMF peptide inhibits the mRNA and protein expression of P-glycoprotein or multidrug resistance related protein-1 (MRP-1), which are major causes of multidrug resistance, and administering the AMF protein or AMF peptide in combination with an anticancer agent inhibits the release of the anticancer agent from cells, thus having the effect of increasing the accumulation of the anticancer agent inside cancer cells. Therefore, the composition can be effectively used as a pharmaceutical composition for inhibiting multidrug resistance to an anticancer agent or as an anticancer adjuvant for multidrug-resistant cancer.

The present invention relates to compounds of Formula (I), as well as prodrugs, pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods of preparation thereof. The compounds disclosed herein are useful in the treatment of diseases in which the expression of P-glycoprotein and / or cytochrome P450 (e.g., CYP3A4) is modulated (e.g., cancers that have developed multi-drug resistance).

The invention discloses an anti-cancer oligopeptide designed based on threonine and analogues thereof and application of the anti-cancer oligopeptide, the anti-cancer oligopeptide is obtained by taking KLLKKLLKKLLKKKLLKW as a structural basis, replacing amino acids at different sites with hydroxyl-containing threonine or analogues thereof, and then amidating a C terminal; the structural general formula of the compound is as follows: KXmLKKLLKKLLKW-NH2, wherein X = T, pT, F, Y or pY, and p represents phosphorylation; and m is 2, 3, 6, 7, 10, 11 or 13. The anti-cancer oligopeptide has the advantages of high efficiency, low toxicity, short sequence and the like. In-vitro anti-tumor activity and toxicity experiment results show that the compound has a relatively strong killing effect on various tumor cells, and is low in hemolytic toxicity and high in therapeutic index. Serum stability experiments further show that the protein has relatively high enzymolysis stability. A scanning electron microscope experiment shows that the anti-cancer oligopeptide can quickly kill tumor cells through an effective membrane rupture mechanism. Therefore, the compound has a good application prospect in the aspects of research on novel high-efficiency low-toxicity polypeptide anti-cancer drugs, resistance to multidrug resistance and preparation of anti-cancer drugs.

One of the purposes of the present disclosure is to: (i) provide a novel bacteriophage having a lysolytic activity against a Salmonella bacterium such as S.Enteridis, or a lysolytic agent comprising the same; (ii) providing a bacteriophage having a broad range of hosts for Salmonella bacteria or a lysozyme comprising the same; (iii) providing a host-specific bacteriophage or an effective bacterial lysozyme of the Salmonella genus comprising the same; or (iv) providing a bacteriophage capable of effectively controlling S.Typhimurium, in particular, S.Typhimurium having a multidrug resistance, or a bacteriolytic agent containing the bacteriophage, which is capable of effectively controlling S.Typhimurium, in particular, S.Typhimurium having a multidrug resistance. The present disclosure provides a bacteriophage having a specific genomic DNA sequence, a Salmonella bacterial lysozyme comprising the same, and a composition comprising the same.

The invention relates to the field of polypeptides, in particular to an NL-1 polypeptide capable of inhibiting a tight reaction and application of the NL-1 polypeptide. The NL-1 polypeptide is screened from transcripts of spiders, and the NL-1 polypeptide is predicted and verified to have antibacterial activity through antibacterial screening. An enzyme activity experiment is utilized to prove that synthesis of a tight reaction signal small molecule ppGpp can be reduced by inhibiting activity of key enzymes PaRelA and PaSpoT in a tight reaction of pseudomonas aeruginosa, so that the tight reaction is inhibited. Meanwhile, a bacteriostatic experiment and a bactericidal dynamics experiment prove that the NL-1 polypeptide grows in a concentration-dependent manner through three hospital-sourced multidrug-resistant pseudomonas aeruginosa strain; meanwhile, the NL-1 can effectively kill multidrug-resistant pseudomonas aeruginosa, in addition, the NL-1 also effectively reduces the generation of a quorum sensing key molecule PQS of the pseudomonas aeruginosa, and the component is proved to be related to antibiotic tolerance. In conclusion, the NL-1 polypeptide disclosed by the invention has a good antibacterial effect, can be used as a novel antibiotic, and has a huge application value for treatment of multidrug-resistant bacteria.

The present disclosure is directed to certain functionalized dual substituted arene derivatives (e.g., arenesulfonamide, arenesulfamide, areneoxalamide and areneamide derivatives) of Formula I; and pharmaceutically acceptable salts thereof, wherein X1, X2, Y, Z, G, R1, R2, R3, R4, and R5 are as defined herein, which are potent inhibitors of MsbA and may be useful in the treatment of infections caused by any multi-drug resistant (MDR) Gram-negative bacteria. The disclosure is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of infections in which MsbA is involved.

The invention described herein generally relates to novel therapeutic compounds, and in particular to carbonic anhydrase inhibitors as a narrow spectrum antibiotics against drug resistant bacteria and methods for treating those infection diseases in mammals using the described carbonic anhydrase inhibitors or a pharmaceutical formulation thereof.

The invention relates to the technical field of biological medicines, in particular to application of dauricine in preparation of a preparation for inhibiting lysosome capture and treating cancers. The dauricine disclosed by the invention has a good lysosome capture inhibition effect, can be further used for preparing a preparation for inhibiting lysosome capture, can be combined with a medicine which is easily captured by lysosome for use to prevent the medicine from being captured by lysosome, can also be used for preparing a preparation for treating cancers, and effectively solves the problem of multidrug resistance of tumors.

The invention provides a polypeptide or a pharmaceutically acceptable salt thereof and application of the polypeptide or the pharmaceutically acceptable salt in preparation of a tumor multidrug resistance reversal agent, and belongs to the technical field of biological medicines. The polypeptide can selectively act on tumor cells with negatively charged cell membranes through electrostatic interaction, has small influence on normal cells, and has good selectivity; meanwhile, a hydrophobic fragment in the structure is inserted into a tumor cell membrane phospholipid skeleton to destroy the integrity of a cell membrane, change the permeability of the cell membrane and inhibit the membrane protein function, so that more anti-tumor drug molecules can be promoted to enter tumor cells, the accumulation of the drug in the tumor cells is improved, the function of ABC transport protein on the membrane can be influenced, and the anti-tumor effect is improved. The excretion of intracellular drugs is inhibited, and finally, the aim of reversing the multidrug resistance of tumors is fulfilled. Therefore, the polypeptide or the pharmaceutically acceptable salt thereof can be used as a novel peptide tumor multidrug resistance reversal agent, can be potentially used in anti-tumor clinical treatment, and has a wide development prospect.

This invention discloses a strain of *Lactococcus gasseri* LG3092 that produces the bacteriocin GarQ and effectively antagonizes multidrug-resistant *Helicobacter pylori*, and its applications. *Lactococcus gasseri* LG3092 was deposited at the Guangdong Provincial Microbial Culture Collection Center on October 30, 2023, with accession number GDMCC No: 63939. Studies have shown that LG3092 has the following beneficial effects: (1) it can produce the bacteriocin GarQ, effectively inhibiting the growth of *Helicobacter pylori* and other common pathogenic bacteria; (2) it has a high survival rate in the stomach, can colonize the stomach, and can compete with pathogenic bacteria for binding sites, effectively reducing the infection rate of *Helicobacter pylori* in the stomach; (3) it can improve the pathological state of the stomach and alleviate inflammation. Therefore, *Lactococcus gasseri* LG3092 has great application potential in the preparation of products for the prevention or treatment of *H. pylori*, especially multidrug-resistant *H. pylori* infection.

This invention relates to compounds of formula (IA), as well as their prodrugs, pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods of preparation. The compounds disclosed herein can be used to treat diseases in which P-glycoprotein and / or cytochrome P450 (e.g., CYP3A4) are regulated (e.g., cancers that have developed multidrug resistance).

The invention relates to a method for preparing antibacterial hydrogel from multifunctional gold nanoparticles. The method comprises the following steps: preparing micromolecule modified gold nanoclusters AGNCs; the invention relates to AGNCs-loaded hydrogel and preparation of a freeze-dried sample of the AGNCs-loaded hydrogel. The preparation method is simple, and the antibacterial effect on sensitive strains and multidrug resistant strains of gram negative bacteria is obvious; aGNCs have the bacterial recognition property and the photo-thermal sterilization property; aGNCs and methyl cellulose are assembled to prepare the dressing (A (at) MC), and gel curing induced by the photo-thermal property of AGNCs can be perfectly attached to wounds in different shapes; in the curing process of the A-coated MC, the wound can be rapidly shrunk, and then the wound healing process is added; the AGNCs are gradually released from the dressing, the antibacterial effect is lasting, the AGNCs are stable and easy to store, and after the AGNCs are assembled through methyl cellulose, the AGNCs have high stability, large-scale production potential and wide clinical application prospects.

The invention discloses a preparation method and application of a bovine serum albumin modified gold platinum-niobium carbide nano-enzyme composite material, and relates to the technical field of nano-enzyme composite material preparation. The invention aims to solve the problems of lack of specificity, cytotoxicity, short half-life period, poor solubility and easy generation of multi-drug resistance of the traditional chemotherapeutic drug, and low efficiency and single anti-tumor means of the pure chemical power therapeutic drug. The method comprises the following steps: firstly, sequentially carrying out etching and stripping treatment on niobium aluminum carbide powder, and then carrying out ultrasonic treatment to obtain a niobium carbide nanosheet solution; and loading gold nanoparticles and platinum nanoparticles on the surface of the niobium carbide nanosheet under the modification of bovine serum albumin to obtain the bovine serum albumin modified gold platinum-niobium carbide nano-enzyme composite material. According to the preparation method and application of the bovine serum albumin modified gold platinum-niobium carbide nano-enzyme composite material, the bovine serum albumin modified gold platinum-niobium carbide nano-enzyme composite material can be obtained.

The invention provides application of a CD5-targeting reagent in the aspects of reducing the drug resistance of tumor cells and improving the anti-tumor curative effect of drugs, and clarifies for the first time that CD5 molecules can promote high expression and cell nucleus displacement of transcription factors FOXO3a and FOXO4 in a forkhead cassette O signal channel; therefore, expression increase of the ABC drug-resistant protein family in diffuse large B-cell lymphoma tumor cells is mediated, and drug resistance of tumor cells to various chemotherapeutic drugs is promoted. Further, it is found that the celecoxib can significantly inhibit expression of CD5 molecule mediated ABC drug-resistant protein in B-cell lymphoma cells, then the celecoxib and chemotherapeutic drugs are combined for application, the killing effect of traditional chemotherapeutic drugs on diffuse large B-cell lymphoma tumor cells is significantly enhanced, and the chemotherapeutic drug resistance of diffuse large B-cell lymphoma is overcome. The anti-drug-resistant tumor strategy can overcome the problems of low treatment response rate and poor prognosis of the CD5-positive diffuse large B-cell lymphoma to the existing chemotherapy regimen due to multidrug resistance, and significantly improves the anti-tumor treatment effect.

This invention provides a peptide-metal cluster probe and its application in the preparation of kits for sorting drug-resistant cells and / or quantitatively detecting cell membrane proteins, belonging to the field of biomedical technology. This invention prepares a peptide-metal cluster probe targeting a multidrug resistance-related protein (P-glycoprotein, P-gp), and utilizes its fluorescence properties to sort mixed tumor cells with different levels of multidrug resistance into different cell subpopulations. Then, laser ablation inductively coupled plasma mass spectrometry (ICP-MS) is used to detect the expression level of P-gp in individual tumor cells within different subpopulations. This rapid and novel optical-mass spectrometry technique can be used for specific tumor cell phenotypic analysis and anti-tumor drug screening. The quantitative analysis of cell membrane protein expression can lay the analytical foundation for drug screening to reverse drug resistance.

Non-responsiveness assessment in IBD patients The present invention relates to an in vitro method for predicting the response of patients with inflammatory bowel disease (IBD) to treatment with intracellular immunosuppressants. In this method, samples are collected from IBD patients in the early stages of treatment with an immunosuppressant of interest, and these samples contain effector mononuclear cells. Responsiveness is predicted based on the difference between the activity level of the multidrug-resistant ABC transporter and the activity level of the reference transporter in effector mononuclear cells in the sample. This method is useful in the treatment of IBD and can be used, for example, to monitor disease progression or to determine whether to switch from the initial treatment to another medication (e.g., csDMARD or tsDMARD).

The invention belongs to the field of medicinal chemistry, and provides a 17 beta-estradiol analogue, a preparation method thereof and application of the 17 beta-estradiol analogue in reversing multidrug resistance of tumors. Research finds that the preferable 17 beta-estradiol analogue II-25 can inhibit the excretion function of a chemotherapeutic drug of ABCB1 protein through interaction with a binding site at the bottom of the ABCB1 protein, increase the drug concentration in cells, effectively reverse the ABCB1-mediated tumor multidrug resistance, inhibit the tumor apoptosis, inhibit the tumor apoptosis, inhibit the tumor apoptosis, inhibit the tumor apoptosis, inhibit the tumor apoptosis, inhibit the tumor apoptosis, inhibit the tumor apoptosis and inhibit the tumor apoptosis. Therefore, the treatment of ABCB1 mediated multidrug resistance tumors is realized through the combination with ABCB1 substrate chemotherapy drugs. The preparation method disclosed by the invention is high in repeatability, good in stability, relatively simple in conditions required by experimental reaction, mild in experimental environment and relatively good in yield, and mass production can be carried out under the condition of relatively small investment. The prepared 17 beta-estradiol analogue can be effectively used for the development of an ABCB1 inhibitor.

Disclosed is a method for treating a condition, which includes the steps of: selecting a patient for treatment who has the condition; administering to the patient at least one active pharmaceutical ingredient (API); and administering to the patient at least one metal complex represented by formula (I):including hydrates, solvates, pharmaceutically acceptable salts and prodrugs thereof. Also disclosed is a composition for conducting the method, which includes: at least one API selected from the group consisting of Cisplatin, Temozolomide, Vandetanib, Withaferin A, Vemurafenib, Amiodarone, Vinblastine, Metformin, Gemcitabine and Acyclovir; and at least one metal complex effective to potentiate an efficacy of the API to treat the condition, wherein the at least one metal complex is represented by formula (I), including hydrates, solvates, pharmaceutically acceptable salts and prodrugs thereof.

The present invention relates to probiotic bacteria of the species E. coli, in particular in combination with bacteria of the species Klebsiella oxytoca, that are used for a decolonization of pathogenic and / or multidrug resistant (MDR) Enterobacteria, such as pathogenic E. coli and / or Klebsiella pneumoniae (K. pneumoniae), Enterococci and / or Acinetobacter, from the gut of a subject. The decolonization can both be therapeutic, i.e. after colonization of the gut by the pathogenic and / or multi-resistant pathogen(s), or as a preventive measure before a re-colonization of the gut, as required after antibiotic treatment or treatment-induced dysbiosis.

The invention provides an SP-1 polypeptide and application of a coding gene of the SP-1 polypeptide in inhibition of tight reaction and antibiosis, and belongs to the technical field of polypeptides. The amino acid sequence of the spider-derived SP-1 polypeptide is as shown in SEQ ID NO: 1. According to the present invention, the SP-1 polypeptide can specifically inhibit Escherichia coli and pseudomonas aeruginosa tight reaction key small molecule (p) ppGpp synthase activity, strong antibacterial activity is represented, and the MIC of the SP-1 polypeptide on Escherichia coli and pseudomonas aeruginosa is 2.4 [mu] M and 1.5 [mu] M respectively, and is significantly lower than the MIC (14.5 [mu] M and 12.3 [mu] M) of kanamycin of a positive control group under the same experiment condition; in addition, the SP-I peptide shows efficient bactericidal activity, the minimum bactericidal concentration of the SP-I peptide to escherichia coli and pseudomonas aeruginosa is 2.0 mu M, and the SP-I peptide can effectively inhibit generation of escherichia coli and pseudomonas aeruginosa biological membranes. Therefore, the SP-1 polypeptide can be used as an active ingredient to be applied to preparation of antibacterial drugs for inhibiting multidrug resistance bacteria.

Multi-drug resistant tuberculosis (TB) is a major public health problem concerning about half a million cases each year. Patients hardly adhere to the current strict treatment consisting of more than 10,000 tablets over a 2-year period. There is a clear need for efficient and better-formulated medications. The inventors have previously shown that nanoparticles made of cross-linked poly-β-cyclodextrins (pβCD) are efficient vehicles for pulmonary delivery of powerful combinations of anti-TB drugs. Here, they report that in addition to be efficient drug carriers, pβCD nanoparticles are endowed with intrinsic antibacterial properties. Indeed, empty pβCD are able to impair M. tuberculosis (Mtb) establishment after pulmonary administration in mice. pβCD hamper colonisation of macrophages by Mtb by interfering with lipid rafts, without inducing toxicity. Moreover, pβCD provoke macrophage apoptosis leading to depletion of infected cells, thus creating a lung micro-environment detrimental to Mtb persistence. Taken together, the results suggest that materials made of cross-linked β-cyclodextrins (e.g. nanoparticles) loaded or not with antibiotics play an antibacterial action by its own and could be used as carrier in drug regimen formulations effective against TB.

The present application relates to a kind of isoquinoline alkaloid derivatives for reversing tumor multidrug resistance by inhibiting autophagy and preparation method and application.The derivative can efficiently reverse the multidrug resistance of various solid tumor cells such as gastric cancer, lung cancer and esophageal cancer, the derivative can inhibit the autophagy flow of tumor cells, it is combined with vincristine, mitoxantrone, colchicine, docetaxel and various chemotherapeutic drugs, can efficiently reverse tumor multidrug resistance in vivo and in vitro, this kind of derivative has excellent oral bioavailability and lower toxic side effects, provides a kind of alternative strategy for autophagy inhibitor as antitumor chemosensitizer, can be used as lead compound for the research and development of new drug-resistant tumor reversing agent.