31 results about "Everolimus" patented technology

The application discloses a kind of rapamycin 40-position hydroxyl alkyl synthesis method, belong to the technical field of drug synthesis.The method is: in inert gas atmosphere, rapamycin is sequentially added into microwave reaction tube, molecular sieve and additive, additive is triphenyl phosphine oxide, tri (4-fluorophenyl) phosphine oxide, tri (4-methoxyphenyl) phosphine oxide, tricyclohexyl phosphine oxide, triphenyl phosphine sulfide, triphenyl phosphine selenide or hexamethylphosphorus triamide;Subsequently, alkylating agent, base and organic solvent are added, sealed, reacted in microwave reaction instrument, cooled, filtered, washed, dried, filtered, purified, to obtain the alkylated product of rapamycin 40-position hydroxyl group.The method compared with the existing rapamycin 40-position hydroxyl group alkyl modification method, simple operation, low cost, short reaction time, less impurities, easy separation, higher yield, up to 79.1%, suitable for industrial production, can provide new ideas for synthesis and development of rapamycin derivatives such as everolimus.

This invention provides a combination for use in treating cancers that express prostate-specific membrane antigen (PSMA). [Solution] A combination comprising a PD-1 inhibitor, a CTLA-4 inhibitor, and a radiolabeled compound of formula Ia for use in treating PSMA-expressing cancer in the subject. JPEG2026049728000042.jpg45132 The aforementioned combination comprises one or more further anticancer agents, wherein the further anticancer agents are selected from octreotide, lanreotide, vapreotide, pasireotide, satreotide, everolimus, temozolomide, telotristat, sunitinib, sulfatinib, ribociclib, entinostat, and pazopanib.

The application discloses a method for simultaneously and rapidly detecting the concentration of four immunosuppressants, comprising the following steps: mixing a blood sample with an internal standard solution containing ascomycin, cyclosporine-d4, sirolimus-d3 and everolimus-d4, adding a precipitant and centrifuging to obtain a sample to be detected; injecting into a liquid chromatography-tandem mass spectrometry system for analysis to obtain original data containing the retention time window and mass spectrum response signal of four analytes; searching the original data based on an interferent database, wherein the interferent database contains a plurality of compounds that can possibly generate mass spectrum signal interference and characteristic ion information thereof; inputting the original data and the searched potential interferent information into a machine learning model to output a net mass spectrum response value after interference correction; and calculating the concentration of tacrolimus, cyclosporine, sirolimus and everolimus in the blood sample according to the obtained net mass spectrum response value, the mass spectrum response value of the corresponding internal standard and a pre-established standard curve.

The application provides a preparation method of everolimus, and the method comprises the following steps: (1) under alkaline conditions, a compound A sirolimus is reacted with an active ester B in an organic solvent to obtain a compound C, which is an intermediate of sirolimus 43 and 28 hydroxyl diether; the reaction temperature is 50-70 DEG C; (2) the compound C is subjected to acid hydrolysis reaction in a solvent to obtain a compound D everolimus, and the reaction temperature is -20-0 DEG C. The preparation method simplifies the process operation process, and has a good industrial application prospect.

The invention provides application of combination of an mTOR inhibitor and an EPAS1 inhibitor in preparation of a medicine for treating myeloproliferative tumors, through combined use of the mTOR inhibitor everolimus and the EPAS1 inhibitor PT2385, JAK2V617F mutation-driven metabolic disorder is targeted, metabolic reprogramming is effectively reversed (the lactic acid level is reduced, the alpha-ketoglutaric acid level is increased, and the lactic acid / alpha-KG ratio is corrected), and the treatment effect on myeloproliferative tumors is improved. The JAK inhibitor can be used for treating MPN, synergistically relieving splenomegaly, reversing myelofibrosis and reducing mutation allele load, the curative effect is remarkably superior to that of existing JAK inhibitor single-drug treatment, and an innovative scheme with disease modification potential is provided for MPN.

The invention discloses a preparation method of an everolimus related substance F, and belongs to the field of pharmaceutical chemicals. The preparation method of the everolimus related substance F comprises the following steps: dissolving everolimus in an ethanol solvent to obtain the everolimus related substance F under the action of oxygen, and combining silica gel column chromatography with semi-preparative separation and purification to obtain a target compound pure product. The invention provides the preparation method of the everolimus related substance F, the reaction conditions are mild, everolimus degradation impurities are generated, the process flow is simple, the product purity is high, and the quality control of everolimus and a preparation thereof is effectively improved.

A medical device may be coated with a therapeutic composition comprising everolimus. The everolimus crystals may be coated with a mixture of excipients to form encapsulated everolimus crystals suspended in the coating composition. The medical device may contact the coating composition to form a coating on the medical device. Coating the everolimus crystal with a mixture of excipients to form an encapsulated everolimus crystal suspended in a coating composition can include suspending the everolimus crystal in a first solution comprising acetyl tributyl citrate (ATBC), and adding a second solution to the first solution; the present invention relates to a method for preparing everolimus crystals, comprising the steps of preparing a first solution comprising everolimus crystals, preparing a second solution comprising ethyl cellulose (EC), mixing the EC with ATBC and coating the everolimus crystals, thereby forming a coating suspension comprising the coated everolimus crystals.

The utility model relates to the technical field of pharmacy, in particular to a synthesis device of everolimus impurities. Comprising a reaction kettle, a stirring mechanism arranged in the reaction kettle and a driving mechanism connected with the stirring mechanism, the reaction kettle is of a three-layer nested structure, and the reaction kettle comprises a reaction kettle body arranged on the inner layer, a temperature adjusting interlayer arranged on the periphery of the reaction kettle body and an outer concentration cavity arranged on the periphery of the temperature adjusting interlayer; the bottom of the outer concentration cavity is communicated with the bottom of the reaction kettle body, a flow control valve is arranged at the communication position, the outer concentration cavity is connected with a condenser through a gas conveying pipe and connected with a vacuum pump through an exhaust pipe, and reaction liquid in the reaction kettle body flows into the outer concentration cavity through the flow control valve under regulation and control of the vacuum pump. And reduced-pressure heating concentration is realized in the outer concentration cavity. The problem of meeting diversified requirements of different reaction steps is solved, and the synthesis efficiency of the everolimus impurity is improved.

Disclosed herein are methods of treating one or more tumors by administering to the subject a therapeutically effective amount of a combination of RAD1901 or solvates (e.g., hydrate) or salts thereof and one or more second therapeutic agent(s) (e.g., everolimus). The cancer is an estrogen-dependent cancer, such as breast cancer, ovarian cancer, colon cancer, endometrial cancer, or prostate cancer.

The invention provides application of detection of enterococcus faecalis in liver cancer tissue in treatment of liver cancer. The invention finds that enterococcus faecalis is highly abundant in liver tumor tissues and is positively correlated with the pathogenesis of HCC (Hepatocellular Carcinoma). Enterococcus faecalis or an enterococcus faecalis conditioned medium promotes liver cancer cell proliferation, protein translation, cell migration and tumorigenesis. Animal experiments prove that colonization of enterococcus faecalis can promote in-vivo growth of liver cancer, and everolimus (an mTOR pathway inhibitor) administration can significantly inhibit the promotion effect. The colonization amount of the enterococcus faecalis can be used as a marker of a liver cancer clinical treatment strategy of colonization of the enterococcus faecalis.

Aspects of the disclosure relate to methods of administering everolimus with peripheral blocker compounds for use in reducing peripheral side effects.

The application discloses a kind of photodynamic balloon catheter systems, comprising: tube body, with opposite proximal end and distal end;Balloon, the balloon is fixed in the distal end portion of the tube body;Optical fiber assembly is inserted in the tube body, and with the light-emitting site extending to adjacent the balloon;The surface of the balloon is loaded with auxiliary material and photosensitizer in the form of coating;The photosensitizer can activate collagen and elastin under the wavelength of light 400-460nm to make them crosslink;The auxiliary material includes active drug and sustained-release material wrapped the active drug, the active drug is at least one of paclitaxel, rapamycin, zotarolimus, tacrolimus, everolimus, temsirolimus, zanolimus, biolimus, docetaxel, protein-bound paclitaxel and protein-bound dexamethasone;By the photodynamic balloon catheter system of the application can improve the utilization rate of active drug in intravascular administration.

The invention relates to the technical field of biological medicines, and discloses application of rapamycin in preparation of a medicine for protecting male reproductive function from damp-heat stress injury. The invention also discloses application of the rapamycin derivative in preparation of a medicine for protecting male reproductive function from damp-heat stress injury. The rapamycin derivative is everolimus, temsirolimus or defolimus. The invention discloses the new application of the rapamycin in preparing the medicine for treating the damp-heat stress caused by the high-temperature and high-humidity environment for the first time, and the action mechanism of the rapamycin is that the rapamycin inhibits an mTOR (mammalian Target of Rapamycin) pathway and activates cell protective autophagy. Animal experiments show that the rapamycin can significantly improve the testosterone concentration of a damp-heat stress model, effectively recover the protein expression of PDGFRalpha and 3beta-HSD, reverse the development process of damaged testicular interstitial cells, and provide a brand new drug choice with a clear action mechanism for preventing and treating the influence of damp-heat stress on a male reproductive endocrine system.

The application discloses a kind of for preventing or treating post myocardial infarction ventricular arrhythmia pharmaceutical composition, the pharmaceutical composition is by everolimus, ethmolam and fluoxetine, belongs to the field of medicine technology.Immunoblotting proves that everolimus, ethmolam and fluoxetine can inhibit fatty acid oxidation protein.In vitro and in vitro cardiac electrophysiology experiment proves that the pharmaceutical composition can effectively reduce post myocardial infarction ventricular arrhythmia susceptibility.TTC staining proves that the pharmaceutical composition can effectively reduce post myocardial infarction myocardial damage area.Based on the above composition in the regulation of post myocardial infarction ventricular arrhythmia susceptibility, it can be further developed in the clinical application of the disease.

The application provides a kind of pharmaceutical composition and its application in preparation anti-tumor drug.The composition is combined by everolimus and a small molecule conjugate, and the small molecule conjugate is BSJ-4-116 in English name.The small molecule conjugate BSJ-4-116 in the composition can significantly reduce CDK12 protein content, inhibit the proliferation of tumor cells.The in-vivo and in-vitro experimental researches prove that the pharmaceutical composition prepared by everolimus and small molecule conjugate BSJ-4-116 in proportion can significantly inhibit the proliferation of colorectal cancer in-vivo and in-vitro, and the anti-tumor effect is better than the effect of everolimus or small molecule conjugate BSJ-4-116 alone.The application provides a new strategy for anti-tumor of colorectal cancer.Lay a foundation for expanding the clinical indications of anti-tumor drug everolimus.Also provides a new medical use for everolimus and small molecule conjugate BSJ-4-116.

An everolimus topical ocular administration formulation, characterized by comprising a therapeutically effective amount of everolimus and following pharmaceutical excipients: (1) a surfactant; (2) water; and (3) other pharmaceutically acceptable pharmaceutical excipients, wherein the surfactant comprises a component A and a component B, the component A being a cyclodextrin excipient and the component B being Tween. Diseases or disorders that may be treated or prevented by the formulation include axial elongation, axial elongation-associated myopia, retinal thinning, retinal degeneration, retinal holes, posterior scleral staphyloma, tessellated fundus, chorioretinal atrophy, macular atrophy, macular retinoschisis, lacquer cracks, Fuchs spots and choroidal neovascularization, and visual impairment associated with these disorders.

The invention provides application of Obg detection in liver cancer tissue in liver cancer treatment. The invention finds that EF-EVs derived from enterococcus faecalis deliver EF-Obg GTPase to activate a host mTOR pathway, thereby promoting liver cancer progression. The enterococcus faecalis Obg gene is very important for the enterococcus faecalis to activate mTOR so as to promote the occurrence of liver cancer, and the engineering Obg knocks down the enterococcus faecalis strain based on a CRISPRi (Clustered Regularly Interspaced Short Palindromic Repeats i) experiment. Clinically, abundant EF-Obg protein expression is related to activation enhancement of mTOR, so that the total lifetime of HCC patients is relatively poor. In addition, the treatment of the mTOR inhibitor everolimus is effective in an enterococcus faecalis colonized liver cancer in-situ model, which indicates that the treatment of everolimus is effective for liver cancer patients rich in enterococcus faecalis.

The invention discloses an MXene and everolimus composite coating and a preparation method and application thereof.The preparation method comprises the steps that MXene nanosheets and everolimus are compounded through hydrogen bonds and pi-pi stacking, the maximum drug loading capacity is 44.4%, and the MXene and everolimus composite coating is further blended with a degradable polymer to prepare the coating, the mass ratio of the MXene and everolimus compound to the degradable polymer is (1: 5)-(1: 15). An in-vitro experiment shows that the coating has a two-phase slow release characteristic, antioxidant activity and efficient antibacterial performance. A biological safety test shows that the hemolysis rate of a coating leaching solution is smaller than or equal to 4.1% + / -0.9%, the endothelial cell survival rate is 87.6% + / -3.8%, the problems of biotoxicity, process and infection of a traditional coating are solved from the source of materials, the coating is suitable for cardiovascular stent surface modification, and the risks of restenosis, oxidative stress and bacterial infection are jointly solved.

This invention relates to the treatment of breast cancer in a subject, and the subject can be either a male or female subject. Including methods of: treating metastatic breast cancer; refractory breast cancer; AR-positive breast cancer; AR-positive refractory breast cancer; AR-positive metastatic breast cancer; AR-positive and ER-positive breast cancer; triple negative breast cancer; advanced breast cancer; breast cancer that has failed selective estrogen receptor modulator (SERM) (tamoxifen, toremifene, raloxifene), gonadotropin-releasing hormone (GnRH) agonist (goserelin), aromatase inhibitor (AI) (letrozole, anastrozole, exemestane), cyclin-dependent kinase 4 / 6 (CDK 4 / 6) inhibitor (palbociclib (Ibrance), ribociclib (Kisqali), lerociclib, abemaciclib (Vorzenio), trilaciclib, lerociclib), mTOR inhibitor (everolimus), trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), alpelisib (Piqray) (an inhibitor of phosphatidylinositol-3-kinase subunit alpha (PI3Kα)), lapatinib, neratinib (Nerlynx), olaparib (Lynparza) (an inhibitor of the enzyme poly ADP ribose polymerase (PARP)), bevacizumab (Avastin), and / or fulvestrant treatments; metastasis in a subject suffering from breast cancer; HER2-positive; treating a subject suffering from ER mutant expressing breast cancer and / or treating breast cancer in a subject, by first determining the 18F-16β-fluoro-5α-dihydrotestosterone (18F-DHT) tumor uptake and identifying said subject as having AR-positive breast cancer based on 18F-DHT tumor uptake, comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound and a cyclin-dependent kinase 4 / 6 (CDK 4 / 6) inhibitor.

The utility model relates to the technical field of medicine production filtering technologies, in particular to a filtering device for everolimus impurity synthesis. Comprising two groups of charging barrels and a group of liquid storage barrels which are arranged side by side, the charging barrels are used for storing mobile phases, the bottom ends of the charging barrels are detachably connected with filter barrels for containing silica gel, the bottom ends of the filter barrels are provided with liquid outlet pipes, the liquid outlet pipes are provided with liquid outlet valves, the bottom ends of the liquid storage barrels are provided with liquid transfer pipes, and the liquid outlet pipes are communicated with the liquid transfer pipes through connecting pipes. A liquid discharging pipe is arranged on the connecting pipe, a liquid discharging valve is arranged on the liquid discharging pipe, and the liquid storage cylinder is connected with a vacuumizing mechanism. The filtering efficiency in the synthesis process of the everolimus impurities is improved.

An intravascular device including a transferable drug coating adhered to an exposed outer surface on the device, the drug coating comprising an anti-proliferative active ingredient and a xanthophyll excipient. The xanthophyll may be selected from the group consisting of lutein, astaxanthin, zeaxanthin, meso zeaxanthin, cryptotaxanthin, tunaxanthin, salmoxanthin, and parasiloxanthin, and mixtures thereof. The anti-proliferative active ingredient may be selected from the group consisting of sirolimus, everolimus, zotarolimus, bioliimus, tacrolimus, pimecrolimus, paclitaxel, and mixtures thereof. The device may be used in the treatment of eye disease.

A blood test method includes: a preparation step of preparing whole blood collected from a subject; a pretreatment step for preparing a sample for analysis by pretreating the whole blood; a separation step in which the sample for analysis is separated by components using a liquid chromatograph; and an analysis step for analyzing the separated component using a mass spectrometry device, the subject being administered with a first immunosuppressant comprising at least one substance selected from the group consisting of tacrolimus, cyclosporin A, everolimus, and sirolimus, and with a second immunosuppressant comprising at least one substance selected from the group consisting of cyclosporin A, everolimus, and sirolimus. The second immunosuppressive agent contains at least one substance selected from the group consisting of mycophenolic acids and metabolites thereof, the separated component contains the first immunosuppressive agent and the second immunosuppressive agent, and when the first immunosuppressive agent is analyzed as a target component in the analysis using the mass spectrometry device, the first immunosuppressive agent is separated from the target component, and when the second immunosuppressive agent is separated from the target component, the second immunosuppressive agent is separated from the target component. When the first immunosuppressive agent is analyzed as a target component, analysis is performed in a positive ion pattern, and when the second immunosuppressive agent is analyzed as a target component, analysis is performed in a negative ion pattern.

The present invention relates to the use of cannabidiol (CBD) preparations for use in the treatment of seizures associated with tuberous sclerosis (TSC). [Solution] In particular, the present invention includes the step of administering everolimus in combination with a reduced dose of cannabidiol (CBD). In an alternative embodiment, the present invention relates to the treatment of seizures associated with tuberous sclerosis in everolimus-untreated patients currently treated with CBD. Preferably, the dose of everolimus is reduced by at least 10%.

The invention discloses a pharmaceutical composition for preventing or treating ventricular arrhythmia after myocardial infarction, and belongs to the technical field of medicines. The pharmaceutical composition is prepared from everolimus, etomadectin and fluoxetine. Western blot proves that everolimus, etomadectin and fluoxetine can inhibit fatty acid oxidation protein. In-vitro and in-vitro cardiac electrophysiological experiments prove that the pharmaceutical composition can effectively reduce the ventricular arrhythmia susceptibility after myocardial infarction. TTC dyeing proves that the pharmaceutical composition can effectively reduce the myocardial injury area after myocardial infarction. Based on the regulation effect of the composition on the susceptibility of ventricular arrhythmia after myocardial infarction, the clinical application of the composition to the ventricular arrhythmia after myocardial infarction can be further developed.

To provide compounds and methods useful for treating mTORC-mediated disorders.SOLUTION: The present invention provides novel rapamycin analogs that are potent mTORC1 inhibitors as measured by pS6K. Unlike rapamycin and everolimus, these compounds do not inhibit pAKT at relatively long time points (for example, 24 hours and 48 hours). These compounds also exhibit improved solubility and improved pharmacokinetics compared to rapamycin.SELECTED DRAWING: None

The invention discloses an application of an mTOR (mammalian target of rapamycin) inhibitor in removing intracellular Brucella. The invention provides any one of the following applications of the mTOR inhibitor: 1) preparing a product for inhibiting brucella infection; 2) preparing a product for inhibiting Brucella from infecting a host; 3) preparing a product for treating Brucella intracellular infection; 4) preparing a product for relieving host liver or spleen enlargement caused by brucella infection; according to the present invention, the mTOR inhibitor everolimus can be used for inhibiting the Brucella infection host, such that the foundation is laid for the treatment of Brucella intracellular infection, and the mTOR inhibitor everolimus can be used for inhibiting the Brucella infection host, such that the mTOR inhibitor everolimus can be used for inhibiting the Brucella infection host.

Aspects of the disclosure relate to methods of administering everolimus with peripheral blocker compounds for use in reducing peripheral side effects.

The invention relates to the technical field of clinical treatment drug monitoring, and particularly discloses a kit for rapidly extracting everolimus through a magnetic bead method and a use method of the kit. The kit comprises a lysis solution, a magnetic bead mixed solution, a type I washing solution, a type II washing solution and an eluent; wherein the lysate comprises a phosphate buffer, EDTA (Ethylene Diamine Tetraacetic Acid), NaCl, zinc sulfate and a nonionic surfactant; the nonionic surfactant is prepared from Tween 40, Triton X-100 and Brij 35, and the nonionic surfactant is prepared from the following components in parts by weight: 40% of Tween; by optimizing and adjusting a lysis solution formula, a magnetic bead mixed solution, a type I washing solution and a type II washing solution, the prepared kit can effectively extract everolimus in whole blood, the average recovery rate reaches 81.19%-93.61%, the matrix effect factor reaches 0.98%-1.20, and meanwhile the precision is high; the kit disclosed by the invention can be adapted to an automatic extraction instrument, an extracted product can be directly used for mass spectrometric detection, experimental steps are simplified, the extraction flux is expanded, and the extraction efficiency is remarkably improved.

The present specification relates to AZD9833 for use in the treatment of cancer and methods of treatment of cancer involving administration of AZD9833 wherein, in each case, the AZD9833 is administered orally once daily at a dose between 25 mg and 450 mg. AZD9833 may be administered alone or its use may be in combination with an additional anti-cancer agent such as a CDK inhibitor, everolimus or an AKT inhibitor.