50 results about "Sirolimus" patented technology

Methods of treating a central airway obstruction (CAO), benign airway stenosis, asthma, chronic obstructive pulmonary disease (COPD), or an airway tumor in a human subject, methods of treating chronic rhinosinusitis (CRS) or chronic rhinosinusitis with nasal polyps (CRSwNP) in a human subject, methods of treating a eustachian tube disorder in a human subject, and devices and systems for performing the methods. A method of treating a central airway obstruction (CAO), benign airway stenosis, asthma, chronic obstructive pulmonary disease (COPD), or an airway tumor in a human subject includes inserting a drug-coated balloon catheter into a target site in a trachea, mainstem bronchus, bronchus intermedius, lobar bronchus, segmental bronchus, or sub-segmental bronchus, wherein the balloon is coated with a coating layer including the therapeutic agent and one or more additives. The therapeutic agent includes paclitaxel, sirolimus, or a derivative thereof. The method includes inflating the balloon to dilate the airway and deliver a therapeutic agent to the airway wall. The method includes deflating the balloon. The method also includes withdrawing the balloon catheter from the target site.

The invention discloses a method for adjusting administration dosage according to adverse reaction risk based on a joint model, and is applied to the field of intelligent medical treatment. In the prior art, the relationship between the sirolimus steady-state valley concentration and the specific adverse reaction cannot be quantified, so that the defect of lack of accurate guidance for clinical medication is caused. Through systematic research, the method determines the individual target valley concentration range through a BKMR model for the first time, obtains individual pharmacokinetic parameters of a patient through a group pharmacokinetic model, and finally determines the medication time and the medication dosage of the patient through Bayesian negative feedback simulation, and the medication time and the medication dosage are used for adjusting a medication scheme. According to the invention, prospective risk prediction of adverse reactions of sirolimus is realized, the treatment safety of children with vascular diseases is remarkably improved, and long-term prognosis of patients is improved.

The invention belongs to the field of intelligent medical treatment, and particularly relates to an individualized administration method for treating a PID child patient by combining sirolimus with voriconazole. The method comprises the following steps: acquiring the age of a PID child patient; based on the age of the PID child patient, determining the dosage of sirolimus when the voriconam is combined, and if the age of the PID child patient is in a [1, 6] year interval, the dosage is [0.100, 0.330] mg / QD; if the age is in the interval of [6, 13], the dosage is [0.280, 0.540] mg / QD. According to the method, the PPK model is formulated for the first time when the PID child patient is combined with the VRC in the SRL mode, the optimal administration dosage is explored based on PPK when the PID child patient is combined with the VRC in the SRL mode, and simple medication dosage guidance is provided for child patients of different age groups; individualized and customized SRL medication guidance can be provided for individuals through a posterior Bayesian method.

The present application provides methods of treating a CNS disorder (such as glioblastoma and epilepsy) in an individual, comprising systemically (e.g., intravenously or subcutaneously) administering to the individual an effective amount of a composition comprising nanoparticles comprising an mTOR inhibitor (such as a limus drug, such as sirolimus or a derivative thereof) and an albumin, optionally further comprising administering a second agent (such as an anti-VEGF antibody, a proteasome inhibitor, or an alkylating agent).

Methods for the treatment of cutaneous vascular conditions and cutaneous proliferative conditions are provided. The methods employ topical administration of mammalian target of rapamycin (mTOR) inhibitors such as sirolimus (rapamycin) and everolimus. Conditions treatable by the disclosed methods include venolymphatic malformations, acne, acne rosacea, periorificial dermatitis, acne vulgaris, cutaneous capillary malformation-arteriovenous malformation (CM-AVM) syndrome, RASopathies, Langerhans cell histiocytosis, non-Langerhans cell histiocytosis, scars, hypertrophic or keloidal scars, Proteus syndrome, PIK3CA-related overgrowth spectrum (PROS), PTEN hamartoma tumor syndromes, cutaneous malignancies and tumors associated with PI3K / AKT / mTOR mutations, keratodermas, acanthosis nigricans, Birt-Hogg-Dubé syndrome, Brooke-Speigler syndrome, cylindromas, and epidermal nevi. Also provided are formulations and pharmaceutical compositions having mTOR inhibitor as principal therapeutically active ingredient useful in practicing the methods.

Provided is an effective agent for the treatment of intractable lymphangiopathy and intractable vascular disease. A therapeutic agent for intractable lymphatic diseases and intractable vascular diseases, which contains sirolimus as an active ingredient, and which is administered orally or via a tube at an administration amount that is determined on the basis of parameters associated with the in-vivo dynamics of sirolimus in a patient suffering from the diseases and the body weight and month age of the patient.

This invention belongs to the field of intelligent healthcare, specifically relating to a personalized dosing method for sirolimus combined with voriconazole in the treatment of PID in children. The method includes: obtaining the age of the PID child; determining the sirolimus dosage when combined with voriconazole based on the PID child's age; if the PID child's age is in the range of [1, 6) years, the dosage is [0.100, 0.330] mg / QD; if the age is in the range of [6, 13) years, the dosage is [0.280, 0.540] mg / QD. This application is the first to develop a PPK model for PID children using sirolimus combined with voriconazole (VRC), and based on the PPK, explores the optimal dosage for PID children using sirolimus combined with VRC, providing concise dosage guidance for children of different age groups; and through posterior Bayesian methods, it can provide individualized sirolimus medication guidance.

To provide a sirolimus-containing powder granule formulation that ensures bioavailability and has improved stability. [Solution] A sirolimus-containing granular preparation containing sirolimus and tocopherol, but not containing hydroxypropylcellulose, and a method for producing a sirolimus-containing granular preparation, characterized by comprising the steps of (1) mixing a solution containing sirolimus and tocopherol with core particles that form the core of the granular preparation in the absence of hydroxypropylcellulose, and (2) drying the mixture obtained in step (1).

The invention provides a blood concentration prediction model based on artificial intelligence and a construction method and application thereof.A whole blood sample of a patient taking sirolimus is collected, the blood concentration is detected through liquid chromatography tandem mass spectrometry, CYP 3A4 / 5, CYP 2C8 and P-gp gene polymorphism is detected in combination with a high-resolution dissolution curve technology, and the blood concentration prediction model based on artificial intelligence is obtained. And constructing a database containing the multi-dimensional data. And training the database by using an extreme gradient lifting algorithm, establishing a high-precision sirolimus blood concentration artificial intelligence prediction model, and developing a mobile equipment end application to realize remote data acquisition and result display. The model is especially suitable for children with Carboxi-like vascular endothelioma, can dynamically monitor the blood concentration in real time, provides refined guidance for clinical treatment, reduces the treatment cost, and improves the treatment effect and safety.

The present invention provides a method for manufacturing a drug-coated balloon and a drug-coated balloon obtained by the method. The method for manufacturing a drug-coated balloon is used to apply a drug coating on the surface of a balloon body prepared in advance and in a filled and expanded state, and the anti-proliferative drug component in the drug coating is one or more of nimustine, carmustine, 5-fluorouracil, fluguanosine, gemcitabine, daunorubicin, doxorubicin, paclitaxel, vinblastine, topotecan, aminoglutethimide, sirolimus, everolimus, and zotarolimus. The drug-coated balloon prepared by the method can effectively ensure that when the balloon enters the human body, the thickness of the drug coating on the balloon surface is more uniform and consistent, thereby improving the clinical use effect.

The present invention relates to nanoparticles comprising sirolimus and albumin, a pharmaceutical composition comprising the same for subcutaneous administration, and a method for preparing the same. In the case of using the preparation method of the present invention, nanoparticles comprising sirolimus and albumin having excellent stability of particle size distribution can be prepared, the prepared nanoparticles can be prepared as a pharmaceutical composition suitable for subcutaneous injection, and the increase in administration dose and the convenience of administration can be improved.

The present invention concerns a pharmaceutical composition for topical administration, comprising sirolimus, solvent, thickener and glycol ether. The invention further concerns a pharmaceutical composition for use in the treatment of skin diseases or skin manifestations of diseases, especially of skin manifestations of tuberous sclerosis complex (TSC). The invention further concerns a method for producing a pharmaceutical composition comprising the steps of (i) providing sirolimus and (ii) forming the present composition.

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 present invention relates to nanoparticles comprising sirolimus and albumin, a pharmaceutical composition for subcutaneous administration, comprising same, and a preparation method therefor. If the preparation method of the present invention is used, nanoparticles comprising sirolimus and albumin and having excellent improved particle size distribution maintenance stability can be prepared, and the prepared nanoparticles can be prepared in a pharmaceutical composition suitable for subcutaneous injection, and thus dosage is increased and convenience of administration is improved.

The present application discloses a sirolimus-albumin composition and a preparation method therefor. The preparation method of the present application incorporates an incubation step before solvent removal via evaporation of liquid having undergone high-pressure homogenization, thereby resulting in more uniform nanoparticles and further improving the physical stability of a nanosuspension and the chemical stability of a formulation without the need for any stabilizer. Compared with marketed products, the sirolimus-albumin composition of the present application can be completely dissolved within 1-3 min, the reconstitution operation is simpler, and a nanoparticle suspension after reconstitution remains stable at 30°C for 24 h, thereby offering greater convenience for clinical use. In addition, the composition of the present application can be stored at room temperature, is convenient to transport, and has a longer shelf life.

The invention belongs to the technical field of biological medicine, and relates to a releasable pegylated sirolimus compound and application thereof. The invention provides a releasable PEGylated sirolimus compound. The compound can be self-assembled to form micelles, prepared into nanoparticles and targeted to immune cells, regulates the release behavior of drugs, reduces the system toxicity and prolongs the biological half-life period. And moreover, the sirolimus-hydrophilic PEG conjugate has a proper hydrophobic sirolimus end and a hydrophilic PEG chain end, can effectively release drugs in immune cells, and is a good carrier for preparing nanoparticles. The invention provides a releasable PEGylated sirolimus compound, a nano-drug and a pharmaceutical composition prepared from the releasable PEGylated sirolimus compound, and application of the releasable PEGylated sirolimus compound in preparation of drugs for reducing immune response.

The present disclosure finds that skin sclerosis can be ameliorated by applying an externally applied skin medicine containing sirolimus to the skin in systemic scleroderma, and thus finds a novel medicine for treating or preventing skin sclerosis in systemic scleroderma.

The invention belongs to the technical field of medicine analysis, and particularly relates to an analysis and detection method of sirolimus impurity G, which can accurately separate and detect the impurity G. The analysis and detection method has the advantages of high detection speed, high specificity, high sensitivity and good repeatability.

Provided herein are methods of inducing immune tolerance to graft cells in a human patient in need thereof comprising administering to the patient (i) the graft cells. (ii) a chimeric FasL protein conjugated to a hydrogel, and (iii) transient sirolimus.

The present application provides a drug coating, a preparation method and a drug balloon catheter, the drug coating comprises an active drug and an adhesive, the active drug is a crystal particle, and the active drug is sirolimus or a sirolimus derivative. The drug coating of the present application comprises an active drug in a crystal form, the drug coating has the advantages of good stability, when it is prepared in a drug balloon catheter, the influence of blood flow flushing on the active drug is small during the balloon expansion transfer process, the loss rate of the active drug during delivery is reduced, the physical force on the blood vessel wall during the balloon expansion process is increased, and the transfer rate of the active drug is increased; after the active drug is transferred to the blood vessel wall in the form of a crystal, the active drug is gradually dissolved and released, and then absorbed by surrounding tissue cells, so that long-term stable release and sustained drug efficacy can be achieved.

The present application provides a suspension of sirolimus, which comprises sirolimus, a stabilizer, an osmotic pressure regulator, a suspending agent, a pH regulator and water; wherein the sirolimus is suspended in the water in the form of solid. The preparation process of the inhalation suspension provided by the present application is simple, and the selected excipients are suitable for use in drugs, so that the preparation provided by the present application is not only safe and reliable, but also low in production cost. The inhalation suspension provided by the present application can be stored at room temperature, and after long-term storage, the particle size of sirolimus in the preparation changes little, and the impurity content is low. The bioavailability of the suspension provided by the present application is much higher than that of oral preparations.

The application relates to the field of medicine preparation, in particular to a sirolimus enteric microcapsule granule and a preparation method thereof. The sirolimus enteric microcapsule granule comprises the following components in parts by weight: 0.1-0.5 parts of sirolimus, 50-80 parts of microcrystalline cellulose, 5-10 parts of an inner layer coating material and 3-8 parts of an outer layer coating material; the inner layer coating material comprises carboxymethylcellulose, and the outer layer coating material comprises Eudragit L100-55. The application is characterized in that the outer layer coating is composed of Eudragit L100-55, so that the granule can smoothly pass through the stomach and reach the intestines; the inner layer coating material is composed of carboxymethylcellulose, after the outer layer coating is dissolved in the intestines, the carboxymethylcellulose absorbs water and expands to form a viscous gel layer, so that the drug release is delayed, and the blood drug concentration can be maintained for a long time.

The invention discloses a hyperlipidemia risk prediction model and a risk prediction system during treatment of TSC by SRL, and belongs to the field of disease model prediction. According to the hyperlipemia risk prediction model disclosed by the invention, three parameters including SRL (Sirolimus) blood drug valley concentration, baseline triglyceride and neutrophil count of an object to be evaluated are input; the output is the risk probability of the to-be-evaluated object suffering from hyperlipemia; large sample data is adopted to train a model, cases suffering from hyperlipemia are positive samples, other cases are negative samples, and the model is selected from XGBoost, a support vector machine, a random forest, a decision tree and LightGBM. The key risk factors of hyperlipemia after SRL treatment are disclosed, accurate prediction of the risk of SRL-related hyperlipemia is achieved, especially the RO-AUC of the XGBoost model reaches 0.95, and the method can be applied to detection instruments, monitoring networks, wearable devices and other scenes.

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 present application, in certain aspects, pertains to methods and compositions for the treatment of a hormone-dependent cancer (such as an endometrial cancer (e.g., endometrioid endometrial cancer) or hormone-receptor positive breast cancer), using a composition comprising nanoparticles comprising sirolimus and an albumin in combination with an estrogen suppressor (such as letrozole or fulvestrant).

This blood inspection method comprises a preparation step for preparing whole blood collected from a subject, a pretreatment step for pretreating the whole blood to prepare an analysis sample, a separation step for separating the analysis sample into individual components by liquid chromatography, and an analysis step for analyzing each of the separated components with a mass spectrometry device. The subject has undergone the administration of a first immunosuppressive agent and a second immunosuppressive agent, the first immunosuppressive agent comprising at least one component selected from the group consisting of tacrolimus, ciclosporin A, everolimus and sirolimus, and the second immunosuppressive agent comprising at least one component selected from the group consisting of mycophenolic acid and metabolites thereof. The separated components include the first immunosuppressive agent and the second immunosuppressive agent. With respect to the method, in the analysis of the components with the mass spectrometry device, the analysis is performed in a positive mode when the first immunosuppressive agent is analyzed as a target component, and the analysis is performed in a negative mode when the second immunosuppressive agent is analyzed as a target component.

The present application relates to the field of medicine, and particularly relates to application of sirolimus combined with immune checkpoint inhibitors in anti-tumor treatment. The present application discloses use of a combination of sirolimus or a derivative thereof and an immune checkpoint inhibitor in preparation of a medicament for treating tumors, a pharmaceutical composition and a kit comprising the combination, and a method for treating tumors by administering a therapeutically effective amount of the pharmaceutical composition or the kit to a tumor patient in need. The combination of the present application has a synergistic effect and is suitable for treating cancer.

This application relates, in certain embodiments, to a method and composition for treating soft tissue sarcomas (STS, e.g., spindle cell sarcoma, solitary fibrous tumor, or leiomyosarcoma) using a composition comprising nanoparticles containing an mTOR inhibitor (e.g., limus drugs, e.g., sirolimus or its derivatives) and albumin in combination with a multityrosine kinase inhibitor (e.g., pazopanib).

The disclosure relates in part to the discovery that slow-flow vascular malformations (which can be venous and / or lymphatic) can be treated using direct intralesional delivery of an active drug, such as but not limited to a mTOR inhibitor, such as but not limited to temsirolimus, or a salt or solvate thereof.