23 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 a medicine for preventing or treating liver toxic and side effects of osimertinib, and belongs to the technical field of medicines. Aiming at liver toxic and side effects caused by osimertinib, the invention provides an effective therapeutic drug, and the autophagy inhibitor relieves death caused by excessive activation of an autophagy pathway in hepatocytes by inhibiting autophagy activated by osimertinib, so that hepatotoxicity caused by osimertinib is relieved. The autophagy inhibitor and osimertinib are combined, so that the survival rate of hepatocytes can be remarkably improved, and liver injury caused in the osimertinib treatment process is reduced. The invention further provides novel application of the hydroxychloroquine or the S-adenosylmethionine in preparation of the medicine for preventing or treating the liver toxic and side effects of the osimertinib, the hydroxychloroquine or the S-adenosylmethionine has a remarkable treatment effect on liver injuries caused by the osimertinib, the medication safety of the hydroxychloroquine or the S-adenosylmethionine is high, and the hydroxychloroquine or the S-adenosylmethionine can be used for preparing the medicine for preventing or treating the liver toxic and side effects of the osimertinib. Good development prospects are realized.

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.

The invention discloses an osthole compound pesticide composition for preventing and treating plant pathogenic fungi and application of the osthole compound pesticide composition. The composition comprises an effective component A and an effective component B, the effective component A is cnidium lactone, and the effective component B is eugenol, azoxystrobin or hydroxychloroquine. The composition is compounded by using the cnidium lactone and eugenol, the cnidium lactone and azoxystrobin as well as the cnidium lactone and hydroxychloroquine as effective components, so that the composition has an obvious synergistic effect on preventing and treating tea leaf spot and tomato gray mold, and the generation of drug resistance and drug resistance of plants can be delayed by compounding the effective components; more choices are provided for prevention and treatment of pathogenic fungi, and the bacillus subtilis has a wide application prospect in prevention and treatment of plant pathogenic fungi diseases.

The invention belongs to the technical field of biological medicines, and particularly relates to a marker for evaluating the curative effect of hydroxychloroquine on treating IgA nephropathy and application of the marker. The marker for evaluating the curative effect of the hydroxychloroquine on the IgA nephropathy is a combination of any one or any two or any three or any four or five of D-ornithine, L-arginine, L-cysteine, L-cystine and D-cysteine. Based on the five markers, a combined prediction model is constructed, the model shows relatively high prediction performance, and an early-stage non-invasive screening method can be provided for clinic and is used for identifying IgAN patients with potential HCQ treatment ineffectiveness.

The present invention relates to a pharmaceutical composition for preventing or treating flavivirus infections. The invention provides a pharmaceutical composition. The pharmaceutical composition comprises at least one of gentamicin sulfate, netilmicin, tobramycin, paromomycin, amikacin, capreomycin, triflurazine, dihydrostreptomycin, hydroxychloroquine, thiolidazine hydrochloride, efavirenz, mitefonew, nystatin, micafungin, bleomycin, remistat, montelukast, norfloxacin, nedaplatin and cephalosporin, and the pharmaceutical composition is prepared from the following raw materials in parts by weight. It is possible to exhibit an excellent growth inhibition or inactivation effect on different species of flavivirus.

Provided herein are methods of treating inherited retinal degeneration in an eye of an individual, wherein the method comprises: administering: (i) hydroxychloroquine to the individual; and (ii) a Fas-inhibiting peptide to the eye, wherein the peptide comprises an amino acid sequence HHIYLGAVNYIY or variant sequence thereof, or a pharmaceutically acceptable salt thereof.

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 invention discloses a double-membrane independently wrapped nano drug delivery system for regulating macrophages and platelets. The nano drug delivery system comprises macrophage membrane coated nanoparticles and platelet membrane coated nanoparticles, the macrophage membrane coated nanoparticles are used for adjusting macrophage immune response and loaded with a Toll-like receptor 7 (TLR7) inhibitor, the platelet membrane coated nanoparticles are used for inhibiting abnormal activation of platelets and loaded with a G protein coupled receptor P2Y12 inhibitor, the TLR7 inhibitor comprises at least one of TJ-M2010-5, hydroxychloroquine, Enpatron and IMO-8400, and the TLR7 inhibitor comprises at least one of TJ-M2010-5, hydroxychloroquine, Enpatron and IMO-8400. The P2Y12 inhibitor is prepared from at least one of ticagrelor, clopidogrel, prasugrel and cangrelor. According to the double-membrane independently-wrapped nano drug delivery system, drugs are efficiently delivered to related damaged cells of an inflammation part by utilizing related cell tropism of two cell membranes, immune disorder caused by macrophage and platelet abnormality is inhibited, diseases induced by immune imbalance are treated, an immune microenvironment is regulated and controlled, and the drug delivery effect is improved. And a new direction is provided for treatment of immune diseases.

The invention provides a method for treating systemic lupus erythematosus through a hydroxychloroquine soluble microneedle, and relates to the field of lupus erythematosus treatment.The method comprises the steps that S100, a hydroxychloroquine (HCQ) soluble microneedle patch is prepared, a mixture of hyaluronic acid and polyvinyl alcohol (PVA) serves as a soluble matrix of the microneedle patch, hydroxychloroquine is evenly loaded in the matrix, and the height of the microneedle is 300-1000 micrometers; according to the application, the microneedle penetrates through the cuticle to directly deliver the hydroxychloroquine to the subcutaneous target region, the first-pass effect and whole body exposure of oral administration are avoided, the retina toxicity and gastrointestinal tract side effects of the hydroxychloroquine are reduced, the height of the microneedle is controlled to be 500-800 microns, the microneedle only penetrates through the epidermal layer and does not touch nerve endings, and painless administration is realized; a patient can operate by himself / herself without assistance of professional medical personnel, a cross-linked structure of hyaluronic acid and a PVA matrix can realize slow release of hydroxychloroquine, and a highly expressed hyaluronic acid receptor at a lupus erythematosus lesion site is targeted through anti-CD44 antibody modification.

The invention discloses a tumor targeted quantum dot as well as a preparation method and application thereof. The method comprises the following steps: S1, preparing a CuInSe2 quantum dot; s2, Ag-CISe / ZnS QDs (Quantum Dots) are prepared; s3, the Ag-CISe / ZnS QDs are modified with folic acid, and Ag-CISe / ZnS / FA QDs are obtained; and S4, modifying hydroxychloroquine on the Ag-CISe / ZnS / FA QDs, so as to obtain Ag-CISe / ZnS / FA / CQ QDs, namely the tumor targeting type quantum dot. The tumor targeting type quantum dot prepared by the invention has the characteristic of targeting tumor cells, has excellent photo-thermal performance, and has huge potential of being combined with a photo-thermal treatment method to be applied to anti-tumor treatment; and a low-cost water-phase synthesis method enhances the clinical application value, and an effective treatment preparation can be provided for mild photo-thermal cancer treatment.

A subject is administered an amount of an active agent effective to treat and / or prevent a neurological disorder, wherein the active agent comprises S-hydroxychloroquine with an enantiomeric excess of at least 20% of the S-enantiomer of hydroxychloroquine. The active agent may further comprise tauroursodeoxycholic acid and / or 3,3'-diindolylmethane. The subject may be diagnosed with a neurological disorder or may be identified as being at risk of developing a neurological disorder. Administering the active agent may at least partially normalize an aberrant level of an indicator characteristic of the neurological disorder.

The invention discloses a method for increasing the exosome secretion amount of mesenchymal stem cells of a 3D culture system, and relates to the technical field of exosome production, the method for increasing the exosome secretion amount of the mesenchymal stem cells of the 3D culture system comprises the following steps: S1, multiplication culture of seed cells; s2, performing 3D system multiplication culture; s3, co-culture treatment of a lysosome inhibitor: adding a complete culture medium containing the lysosome inhibitor to carry out co-incubation culture treatment on the mesenchymal stem cells; s4, harvesting cell culture supernatant and extracting exosomes: extracting high-purity exosomes by combining multi-stage membrane filtration, a tangential flow ultrafiltration concentration system and an ultracentrifugation technology; a lysosome inhibitor hydroxychloroquine is added into a 3D culture system to inhibit the effect of lysosomes in cells, and large-scale amplification of mesenchymal stem cells and efficient secretion of exosomes are achieved; the exosomes are extracted by adopting multi-stage membrane aperture precise graded filtration and coupling a tangential flow ultrafiltration system with an ultracentrifugation technology, so that the purity of the exosomes is remarkably improved.

The application provides a preparation method and application of a targeting co-delivery system based on pMMP-1 and hydroxychloroquine. Retinol with specific targeting for activated hepatic stellate cells is selected as a modification group, a targeting nano drug delivery system is obtained after modification of a delivery carrier, and pMMP-1 with negative electricity is electrostatically adsorbed by using the positive electricity of PR, HCQ, an autophagy inhibitor, is wrapped at the same time of electrostatic adsorption, and a targeting co-delivery system based on pMMP-1 and HCQ with active targeting effect for aHSCs is obtained. The application inhibits autophagy of aHSCs, reduces energy supply for activation of aHSCs, reduces expression of fibrosis related proteins, promotes degradation of ECM, and blocks the promotion effect of mechanical force generated by ECM on activation of HSCs. The application not only inhibits activation of HSCs but also degrades ECM deposited outside HSCs, so that a synergistic anti-hepatic fibrosis treatment effect is better achieved, the problem of complex causes of hepatic fibrosis and poor effect of single treatment method is solved, and the application has a good clinical application prospect.

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 invention discloses a compound having a hydroxychloroquine tetravalent platinum structure, a preparation method thereof, and an application thereof. The compound having a hydroxychloroquine tetravalent platinum structure provided by the present invention has a structure as shown in formula (1). The present invention introduces hydroxychloroquine, which has the ability to inhibit autophagy, into a tetravalent platinum structure, and designs and prepares a hydroxychloroquine tetravalent platinum complex. This type of compound exerts an anti-tumor effect through a synergistic anti-cancer mechanism of DNA damage, autophagy inhibition, tumor microenvironment regulation, and immune activation, overcoming the problem of drug resistance of current divalent platinum (II) drugs, significantly improving anti-tumor activity, and reducing toxicity. It is a new type of platinum (IV) drug with the potential to inhibit tumor proliferation and tumor metastasis.

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.