11 results about "Hydroxychloroquine" patented technology

AAV vectors are ideally suited for long-term delivery of a combination of broadly neutralizing antibodies to achieve sterilizing immunity to HIV. Unfortunately, host immune responses to the delivered antibody have severely limited the efficacy. The TLR9 pathway has been identified in initiating adaptive immune responses against AAV and delivered bNAbs. To enhance this strategy, we validated Hydroxychloroquine, a known drug inhibitor of the TLR9 pathway, as a pretreatment to AAV delivery to avoid anti-drug antibody responses. TLR9 signaling inhibition was validated using a HEK-Blue hTLR9 reporter cell line and CpG stimulation. Hydroxychloroquine was also validated in a 3-macaque trial where AAV9-3BNC117 and AAV9-10-1074 were administered along with 3 doses of hydroxychloroquine once a week starting 1 week before AAV inoculation. Unlike historical controls, where 3BNC117 and 10-1074 expression is lost within the first 4-5 weeks, 2 macaques maintained 10-1074 expression and 1 macaque maintained 3BNC117 for the duration of the trial. Anti-3BNC117 antibodies were only observed in 2 of the 3 macaques and were significantly delayed. Anti-10-1074 antibody responses were a log lower than typically observed in historic controls. The use of hydroxychloroquine as a pretreatment for AAV inoculation is a promising strategy. The significant decrease in anti-10-1074 antibody levels and the successful delivery of 10-1074 in 2 macaques and 3BNC117 in 1 macaque was very encouraging. Extending the dosage of hydroxychloroquine beyond 3 doses may be sufficient to observe long-term bNAb expression in all animals and further decrease ADA responses. Together, these data suggest that the short-term treatment of hydroxychloroquine at the time of AAV inoculation has a meaningful impact on tolerance induction to our AAV-delivered bNAbs.

The invention discloses application of hydroxychloroquine to improvement of gene editing efficiency. The invention provides novel application of hydroxychloroquine, namely application of hydroxychloroquine in improving gene editing efficiency of a gene editing reagent on a receptor biological material. In the prior art, a research of combining hydroxychloroquine and gene editing efficiency is not seen. The inventor of the invention finds that the gene editing efficiency can be remarkably improved by treating a receptor biological material with hydroxychloroquine and then transfecting a gene editing reagent. The method is easy and convenient to operate and wide in applicability, and a new way for improving the editing efficiency is developed by introducing exogenous small molecules instead of directly modifying a gene editing tool. The invention provides a basis for exploring an editing efficiency improvement strategy by adding exogenous molecules instead of modifying an editor mutant.

The application provides a preparation method and application of a double-membrane fusion targeted nano drug delivery system, a targeted material Cholesterol-PEG2000-RT modified liposome loaded with hydroxychloroquine is prepared, then the similarity of the liposome and the membrane component of the exosome is utilized, and the fusion of the two is realized through an extrusion method, so that the double-membrane fusion targeted drug delivery system for activating hepatic stellate cells is prepared. The double-membrane fusion targeted nano drug delivery system can not only exert the synergistic anti-hepatic fibrosis treatment effect of hydroxychloroquine and the exosome, but also can realize the specific targeted autophagy inhibition of hydroxychloroquine on activated hepatic stellate cells, so that the further proliferation and differentiation of the activated hepatic stellate cells are prevented, the generation of fibrosis-related proteins is reduced, the anti-hepatic fibrosis effect is exerted, and in addition, the genes and active factors carried by the exosome derived from bone marrow mesenchymal stem cells can exert the liver protection and synergistic anti-hepatic fibrosis effect, so that a new thought and method are provided for the clinical treatment of hepatic fibrosis.

This invention relates to the field of pharmaceutical biotechnology, providing the application of aminoquinoline compounds (such as hydroxychloroquine and chloroquine) in the preparation of drugs for treating hyperparathyroidism. These compounds restore the expression of calcium-sensitive receptors (CaSRs) on the cell membrane surface by inhibiting the lysosomal degradation pathway of CaSRs in parathyroid cells. Experiments have confirmed that 4-aminoquinoline compounds, used alone or in combination with calcimimetics (such as cinacalcet), significantly reduce serum PTH and calcium levels in a model of refractory secondary hyperparathyroidism (SHPT) and inhibit glandular hyperplasia. In particular, the combination therapy regimen exhibits a significant synergistic effect, effectively reversing calcimimetics resistance. This invention is the first to discover a novel use for the antimalarial / antirheumatic drug hydroxychloroquine in the treatment of hyperparathyroidism, realizing a new use for an existing drug; and providing a safe and effective new drug treatment strategy for clinically refractory SHPT.

The application discloses application of chrysin in preparation of a medicine for treating primary Sjogren's syndrome and belongs to the technical field of biological medicine. The application proves that chrysin can be specifically combined with TNFR2 protein and is a new type of TNFR2 inhibitor through molecular docking, molecular dynamics simulation, CETSA experiment and SPR experiment. Animal experiments show that chrysin can significantly increase the secretion amount of saliva and tear of a mouse model of primary Sjogren's syndrome, reduce the serum SSA and SSB antibody levels, reduce lymphocyte infiltration and acinus atrophy of submandibular glands and lacrimal glands, inhibit the expression of a cytokine INF-gamma, and the drug efficacy is equivalent to that of a positive medicine hydroxychloroquine; chrysin and gaoshunyujin have a synergistic effect, and the improvement effect on primary Sjogren's syndrome is better than that of hydroxychloroquine. The application provides a new medical use of chrysin, and provides a safe and effective prevention and treatment medicine for primary Sjogren's syndrome.

A composition for preventing or treating a TNF-α-related disease is disclosed. The composition includes hydroflumethiazide or a pharmaceutically acceptable salt thereof as an active ingredient. The composition can effectively inhibit the expression or activity of TNF-α and exhibits an excellent treatment effect compared to methotrexate (MTX) or hydroxychloroquine (HCQ), which are rheumatoid arthritis treatment agents currently on the market, and, thus, can be effectively used for prevention or treatment of a TNF-α-related disease.

The present disclosure relates to an effect of inhibiting cancer metastasis by treatment of chlorphenesin and hydroxychloroquine alone or in combination. Chlorphenesin or hydroxychloroquine has the effect of inhibiting the metastasis and invasion of cancer cells. In particular, since it was identified that a combination thereof has a synergistic action, it is possible to effectively prevent or treat cancer metastasis by administering chlorphenesin and hydroxychloroquine respectively or in combination thereof.

The application provides an activated endothelial cell membrane-coated nanoparticle, a preparation method, application and a pharmaceutical composition, and belongs to the technical field of biomedical materials. The nanoparticle is composed of a rutin / hydroxychloroquine self-assembled nanoparticle core coated by brain microvascular endothelial cell membranes pretreated by TNF-alpha. The application screens a specific molar ratio of rutin and hydroxychloroquine. The preparation can be combined with the specific binding of ICAM-1 and integrin alpha M beta2 on the surface of neutrophils, and can be carried by neutrophils to cross the blood-brain barrier, realize parenchymal brain targeting enrichment, and synergistically exert anti-inflammatory, antioxidant, NETs formation inhibition and neuroprotective effects, thereby significantly improving ischemic stroke reperfusion injury.

The invention relates to the field of biomedicine, and discloses application of an HLA-B * 27: 04 allele in preparation of a product for evaluating the risk of drug rash caused by hydroxychloroquine. The application comprises the step of predicting the medication risk of a subject by detecting whether the subject carries the HLA-B * 27: 04 allele or not. The HLA-B * 27: 04 allele is found to be strongly related to the drug rash caused by the hydroxychloroquine for the first time and can be used as a risk genetic marker of the drug rash caused by the hydroxychloroquine. In practical application, the risk of drug eruption of a subject needing to be treated by using hydroxychloroquine can be predicted by detecting whether the HLA-B * 27: 04 allele is carried by the subject, and the risk of drug eruption caused by hydroxychloroquine of the subject carrying the HLA-B * 27: 04 allele after the subject uses hydroxychloroquine is obviously higher than that of a non-carrier. The detection product provided by the invention is high in specificity, high in positive predictive value and good in clinical application prospect.

The present application relates to the technical field of medicine, and particularly discloses application of chiral hydroxychloroquine or a pharmaceutically acceptable salt thereof in preparation of a drug for preventing and treating immune diseases. The chiral hydroxychloroquine or the pharmaceutically acceptable salt thereof has a better inhibition rate and a lower cell survival rate on pathological cell proliferation caused by immune diseases, including but not limited to fibroblast-like synoviocytes; the chiral hydroxychloroquine or the salt thereof combined with methotrexate / ilaris (including but not limited to) can reduce the toxic side effects on normal cells and the cell survival rate, and has a better treatment effect on immune diseases.

AAV vectors are ideally suited for long-term delivery of a combination of broadly neutralizing antibodies to achieve sterilizing immunity to HIV. Unfortunately, host immune responses to the delivered antibody have severely limited the efficacy. The TLR9 pathway has been identified in initiating adaptive immune responses against AAV and delivered bNAbs. To enhance this strategy, we validated Hydroxychloroquine, a known drug inhibitor of the TLR9 pathway, as a pretreatment to AAV delivery to avoid anti-drug antibody responses. TLR9 signaling inhibition was validated using a HEK-Blue hTLR9 reporter cell line and CpG stimulation. Hydroxychloroquine was also validated in a 3-macaque trial where AAV9-3BNC117 and AAV9-10-1074 were administered along with 3 doses of hydroxychloroquine once a week starting 1 week before AAV inoculation. Together, these data suggest that the short-term treatment of hydroxychloroquine at the time of AAV inoculation has a meaningful impact on tolerance induction to our AAV-delivered bNAbs.