40 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 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 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 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 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 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.

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.

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.

The application provides a supercritical CO2 assisted preparation of quercetin nanoparticles and application thereof to resisting gastric cancer stem cells. The nanoparticles are prepared by encapsulating quercetin with polylactic acid-co-ethylene glycol (PLGA), so as to solve the problems of poor water solubility and low bioavailability of quercetin and improve the inhibiting effect of quercetin on gastric tumor stem cells. Through a specific preparation process, quercetin-PLGA nanoparticles (Qu-PLGA NS) with uniform particle size and uniform dispersion are obtained. Experimental results show that the Qu-PLGA NS can effectively inhibit the growth and proliferation of gastric tumor stem cells, induce apoptosis of the gastric tumor stem cells, and significantly reduce the invasion and metastasis ability of the gastric tumor stem cells. In addition, the nanoparticles can also reverse the multi-drug resistance of the gastric tumor stem cells, improve the curative effect of a chemotherapeutic drug, and reduce side effects. The application provides a new idea and method for the treatment of gastric cancer and has important clinical application value.

This invention belongs to the field of biomedical technology and discloses a paclitaxel reduction-responsive prodrug micelle with high encapsulation efficiency and its preparation method. The paclitaxel-loaded reduction-responsive prodrug micelles prepared in this invention use biocompatible polyethylene glycol (mPEG) and the drug indomethacin (IND) as the hydrophilic and hydrophobic ends of the micelles, respectively, exhibiting synergistic antitumor effects. Simultaneously, it can reverse multidrug resistance to paclitaxel, increase the sensitivity of drug-resistant cells to paclitaxel, and introduce disulfide bonds between the hydrophilic and hydrophobic ends as a linker arm for reduction-sensitive response, responding to the high concentration of GSH in tumor cells to achieve targeted and precise drug release within tumor cells. This prodrug micelle achieves the goals of solubilizing poorly soluble drugs, tumor targeting, and precise drug release at tumor sites, thus enhancing drug efficacy.

The present invention provides compounds for the regulation of P-glycoprotein and cytochrome P450 (e.g., CYP3A4 and CYP3A5 isoforms) enzymes, which a) significantly improve the bioavailability of substrates of these enzymes, including anticancer drugs, b) overcome multidrug resistance in tumors, and c) reduce serious side effects while improving the delivery of P-glycoprotein substrates to the brain. [Solution] Compounds of formula (I), as well as their prodrugs and pharmaceutically acceptable salts, are provided. Further disclosure relates to pharmaceutical compositions containing the compounds, methods of use, and methods for preparing them. TIFF2026086798000135.tif39128

The invention relates to the technical field of antibacterial materials, in particular to gold nanoparticles modified by methoxyphenol derivatives as well as a preparation method and application of the gold nanoparticles. The gold nanoparticles modified by the methoxyphenol derivatives, provided by the invention, have a spectral antibacterial property, and have a good antibacterial effect on gram-positive bacteria and gram-negative bacteria. In addition, the gold nanoparticles modified by the methoxyphenol derivatives provided by the invention can inhibit efflux pump and transmembrane transport depending on proton dynamic potential, and a reverse inhibition effect on a multidrug resistance mechanism is formed. Pi-Pi and hydrogen bonds provided by the methoxyphenol aromatic skeleton are beneficial to multi-point weak combination with polysaccharide / protein in the extracellular polymeric substance, so that the viscoelasticity of a matrix network is weakened, the formation of a bacterial membrane is inhibited, and the depolymerization of the existing bacterial membrane is promoted.

The present technology provides a combination approach for treating multidrug resistant cancer. Multidrug resistant cancers have more mitochondrial networks than drug sensitive cancers. A first agent fragments mitochondrial networks, dissociates mitochondria from the endoplasmic reticulum, and lower the threshold for apoptosis. A second active agent induces the unfolded protein response, causing stress to the endoplasmic reticulum and limiting the ability of multidrug resistant cancer cells to grow and survive. A third active agent directly activates mitochondrial apoptosis, leading to death of the cancer cells. The active agents can be combined into a nanoparticle formulation for simultaneous delivery into multidrug resistant cancer cells. The formulation serves as a nanomedicine for treatment of multidrug resistant cancers such as multidrug resistant triple negative breast cancer.

The invention discloses a preparation method of a polyisopentenyl acyl phloroglucinol compound, the compound is subjected to a tumor multidrug resistance reversing activity test, under the same concentration, hyperiumono C shows a reversing effect superior to that of a positive drug verapamil, the reversing multiple reaches 56, and the compound has a good anti-tumor effect. A lead compound with development potential is provided for overcoming breast cancer chemotherapy drug resistance.

The application provides a use of Tibetan tea or an extract thereof in preparation of a chemotherapy drug sensitizer, and belongs to the field of medicines. The application first finds that the water extract of Tibetan tea can significantly down-regulate the expression of a multi-drug resistance transporter P-gp in human hepatoma HepG2 cells, inhibit the proliferation of the human hepatoma HepG2 cells, reduce the drug resistance of the HepG2 cells, and enhance the sensitivity of the hepatoma cells to a chemotherapy drug paclitaxel. The application also first finds that the water extract of Yaan Tibetan tea and the paclitaxel play a synergistic effect in inhibiting the expression of the multi-drug resistance transporter P-gp in the human hepatoma HepG2 cells. The water extract of the Tibetan tea combined with the paclitaxel is used for treating hepatoma, and has a good application prospect.

The invention discloses a CLL-1 targeting chimeric antigen receptor NK cell as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. According to the umbilical cord blood-derived CLL-1-targeting chimeric antigen receptor NK cell provided by the invention, accurate recognition of the target cell is realized, and the risk of related graft versus host disease is relatively low. According to the method, the CAR mRNA is delivered by adopting the lipid nanoparticles, so that efficient and safe transfection of the umbilical cord blood NK cells is realized. Through combined use of the CAR-NK cell and an NKG2A inhibitor, an immunosuppression signal mediated by up-regulation of HLA-E molecules on the surface of a tumor cell can be effectively blocked, and the ability of the CAR-NK cell to remove tumors is significantly enhanced; the invention provides an effective combination strategy for solving the problem of adaptive drug resistance in the treatment process of the multidrug-resistant acute myelogenous leukemia and improving the durability of the curative effect.

The present invention relates to the field of therapeutics and, more in particular, to pharmaceutical compositions for the prevention and / or treatment of bacterial infections and antibacterial-induced dysfunctions. The compositions of the present invention demonstrate high species-specificity in inhibiting the growth of a small number of bacterial species, and most importantly are effective also against multi drug resistant (MDR) clinical isolate species. Interestingly, one of those combinations pairs a non-antibiotic drug, vanillin, with an antibiotic drug, spectinomycin, to demonstrate a surprisingly strong inhibitory effect on the growth of clinically relevant Gram-negative pathogenic and multi-drug resistant E. coli isolates. A second set of compounds combines the polymyxin colistin with loperamide, a rifamycin, or a macrolide. Importantly, this invention relates to combinations that enable narrow-spectrum antibacterial therapies, constituting a major effort of current and future drug development efforts in order to prevent major side effects of antibacterial strategies. This invention also relates to pharmaceutical combinations useful to prevent an adverse effect on the gut microbiome, induced by the use of antibacterial compounds.

The application provides application of a compound IMD-0354 in preparation of a drug for treating tuberculosis, and belongs to the technical field of drugs.The compound IMD-0354 screened from a compound library has a significant inhibitory effect on multidrug-resistant Mycobacterium tuberculosis Mtb28 and Mtb1731 and Mycobacterium tuberculosis MtbH37Rv, and has a wide application prospect in preparation of the drug for treating tuberculosis.

The present application relates to a kind of macrocyclic diterpenoids isolated from Euphorbia tirucalli and method and application, after the above-ground part of Euphorbia tirucalli is crushed, at room temperature, with ethanol extraction, solvent is evaporated under reduced pressure to obtain Euphorbia tirucalli crude extract extract, again, the crude extract extract is dispersed with water, and ethyl acetate is added to extract, until the organic phase is colorless, the organic phase layer is combined, and solvent is evaporated under reduced pressure to obtain ethyl acetate extract extract;Again, by normal phase silica gel column, reverse phase C 18 8 pseudo-alangui macrocyclic diterpenoids are obtained by column chromatography, and the anti-inflammatory, antitumor and multidrug resistance reversal activity of the 8 compounds are determined, and the results show that the 8 pseudo-alangui macrocyclic diterpenoids obtained have different degrees of anti-inflammatory, antitumor and multidrug resistance activity, and have potential for preparing related drugs.

N-Functionalized Indole Compounds as Antimicrobial Agents and Process for Preparation Thereof The present invention relates to novel N-functionalized indole compounds and their synthesis using ionic liquids as green reagents and / or solvents in a two to four-step process. The compounds exhibit potent antibacterial activity against multi-drug resistant and susceptible gram-positive bacteria, including Staphylococcus aureus and Enterococcus sp. Synergistic effects are observed when combined with gentamicin or levofloxacin, including activity against resistant MRSA (NRS 119). In-vivo efficacy is demonstrated in a murine skin infection model via topical and oral administration.