144 results about "Tacrolimus" patented technology

The invention belongs to the technical field of biological medicine and data processing, and particularly relates to a multi-modal-based liver transplantation drug dosage prediction method, which comprises the following steps: collecting clinical data of liver transplantation recipients and processing to obtain a sample set, and dividing the sample set into a training set and a test set; constructing a multi-modal linear regression model; samples in the training set pass through a feature extraction module to obtain an original feature sequence; inputting the original feature sequence into a feature dimension reduction module to obtain a dimension reduction feature sequence; inputting the dimension reduction feature sequence into an attention mechanism module to obtain an enhanced feature sequence; the enhanced feature sequence passes through a multi-modal fusion module to obtain a fused feature sequence; inputting the fused feature sequence into a prediction module to obtain a prediction result, and training optimization model parameters; obtaining to-be-processed clinical data, inputting the to-be-processed clinical data into the trained multi-modal linear regression model, and obtaining a medicament dosage prediction result; according to the method, the individualized dosage of tacrolimus can be accurately predicted.

The invention relates to the technical field of plasma concentration monitoring methods, in particular to a method for rapidly detecting the content of tacrolimus in plasma through paper spray mass spectrometry. The method provided by the invention comprises the following steps: adding a to-be-detected plasma sample into a precipitation solution, vortex, taking supernate, and dropwise adding the supernate onto a paper base; spraying voltage is applied to the paper base, the paper base generates electrospray, and the electrospray enters a mass spectrometer for detection; preparing a gradient matrix matched tacrolimus standard solution, replacing the to-be-detected plasma sample with the gradient matrix matched tacrolimus standard solution, repeating the operation, recording a detection result, and drawing a standard curve by taking the matrix matched tacrolimus concentration as an abscissa and taking peak area data acquired by a mass spectrometer as an ordinate; and comparing the recorded detection result with the drawn standard curve, and quantitatively analyzing the content of tacrolimus in the to-be-detected plasma sample. The method disclosed by the invention is simple to operate and high in analysis speed, has relatively good precision and accuracy and also has high sensitivity and high selectivity.

The invention discloses an active exosome stent coating based on traditional Chinese medicine enhanced secretion promotion and a preparation method and application thereof, and belongs to the technical field of biological medicine and interventional instruments. The stent coating comprises exosomes, wherein the exosomes comprise myocardial cell active exosomes and human mesenchymal stem cell active exosomes which are intensified and secreted by traditional Chinese medicines; wherein the traditional Chinese medicines comprise placenta extract, pilose antler extract, sheep myocardial peptide, sea cucumber peptide, lycium ruthenicum peptide, cnidium lactone, curculigo orchioides extract and morinda officinalis extract; the intervention concentration of each component added into cells is 2-50 [mu] g / mL; the light-cured gel matrix is prepared from methacrylated gelatin, a photoinitiator and polyether 127; tacrolimus; the final concentration of the exosome is 1 * 10 < 9 >-12 * 10 < 9 > particles / mL, and the final concentration of the tacrolimus is 5-25 mu g / mL. The coating can be coated on the surface of the poly-L-lactic acid degradable stent to prepare the degradable stent, and has obvious vascular repair promoting capability.

The present invention relates to the use of cannabidiol (CBD) in the treatment of patients with childhood-onset epilepsy who are concurrently taking immunosuppressant drugs. In particular the immunosuppressant drug is a calcineurin inhibitor. More particularly the immunosuppressant drug is tacrolimus. Where the CBD is used in combination with an immunosuppressant drug, caution should be taken. For example, the dose of either the CBD and / or the immunosuppressant drug may be required to be reduced. Moreover, the patient may need to be monitored for side effects of said drug-drug interaction. Preferably the CBD used is in the form of a highly purified extract of cannabis such that the CBD is present at greater than 98% of the total extract (w / w) and the other components of the extract are characterised. In particular the cannabinoid tetrahydrocannabinol (THC) has been substantially removed, to a level of not more than 0.15% (w / w) and the propyl analogue of CBD, cannabidivarin, (CBDV) is present in amounts of up to 1%. Alternatively, the CBD may be a synthetically produced CBD.

The invention relates to the field of drug concentration detection, in particular to a rapid tacrolimus drug concentration detection device based on a micro-fluidic chip. The detection device comprises a blood sampling area, a separation area, a liquid medicine storage area, a waste liquid storage area and a spectrograph, the separation area is used for separating a tacrolimus medicine in a blood sample solution, and a liquid medicine sample and a waste liquid sample are obtained; the spectrograph is used for collecting liquid medicine spectral data of the liquid medicine sample in the liquid medicine storage area and waste liquid spectral data of the waste liquid sample in the waste liquid storage area, and detecting the concentration of the tacrolimus medicine in the blood sample solution according to the liquid medicine spectral data and the waste liquid spectral data. According to the invention, the accuracy of detecting the concentration of the tacrolimus drug in the blood can be improved.

To provide a medicine for improving the state of pregnancy.SOLUTION: The present invention provides a pharmaceutical composition for improving pregnancy conditions in a human subject with pregnancy complications, comprising tacrolimus or a pharmaceutically acceptable salt thereof as an active ingredient, where the human subject has a history of repeated implantation failure (RIF), infertility, or pregnancy-induced hypertension.SELECTED DRAWING: None

The invention discloses a tacrolimus detection kit and application thereof. The tacrolimus detection kit comprises a reagent R1, a reagent R2, a reagent R3, a standard substance, a reagent tube A, a reagent tube B, a reagent tube C and a freeze-drying bottle, wherein the reagent tube A, the reagent tube B, the reagent tube C and the freeze-drying bottle are respectively used for the reagent R1, the reagent R2, the reagent R3 and the standard substance; the reagent R1 is a magnetic bead antibody working solution; the reagent R2 is an enzyme-labeled antigen working solution; the reagent R3 is a blood sample treatment solution, which is a TBS buffer solution containing EDTA-2Na (Ethylene Diamine Tetraacetic Acid), a zinc sulfate solution, Triton X-100 and ProClin300; the standard substance is a freeze-dried whole blood standard substance containing tacrolimus. According to the tacrolimus detection kit and the application thereof, the general blood sample treating fluid is adopted, so that the reliability and the stability of a detection result of tacrolimus in a blood sample are improved.

The present disclosure relates to methods of treating a disease or disorder (e.g., cancer) with an mTOR inhibitor. In particular, the present disclosure relates to methods of treating a subject having cancer by administering specific doses of an mTOR inhibitor. In some embodiments, the present disclosure includes methods for delaying, preventing, or treating acquired resistance to a RAS inhibitor using a dose of an mTOR inhibitor. In some embodiments, the present disclosure relates to methods of using tacrolimus to treat or prevent adverse events associated with the administration of an mTOR inhibitor.

The invention discloses an NK cell serum-free medium, the serum-free medium comprises a basic medium and an additive, the additive comprises the following components: recombinant human transferrin, recombinant human insulin, human serum albumin, growth factors, glucose, trace elements, tacrolimus and mevalonic acid, the serum-free culture medium comprises the following components in percentage by weight: 85% of a basic culture medium, 3% of recombinant human transferrin, 3% of recombinant human insulin, 2% of human serum albumin, 2% of growth factors, 2% of glucose, 1.5% of trace elements, 1% of tacrolimus and 0.5% of mevalonic acid; according to the serum-free culture medium for the NK cells, growth and differentiation of the NK cells can be adjusted by adding a proper amount of tacrolimus, meanwhile, a proper amount of mevalonic acid is matched, raw materials of active substances can be provided for the cultured NK cells, growth and development of the NK cells or expression of specific functions are facilitated, and therefore the survival rate and the amplification number of the NK cells can be increased.

The invention provides application of FXR protein as a target spot in preparation of a medicine for relieving and / or treating renal toxicity of tacrolimus, and belongs to the technical field of biological medicine. The invention proves that the activity or expression level of the FXR protein is regulated in a targeted manner, so that the Tacrolimus-induced renal tubule epithelial cell vacuolation and renal tubule injury can be effectively prevented or relieved, and the abnormal rise of early renal injury markers such as urine NAG enzyme and the like is reduced, thereby directly improving the renal toxicity problem of Tacrolimus. The invention provides a new drug action target and a treatment strategy for clinic, and by developing an FXR agonist or a gene intervention means, the long-term renal injury risk of tacrolimus can be reduced while the anti-rejection curative effect is maintained, the transplanted kidney function and the survival time of a patient are prolonged, and the clinical application prospect is wide. And an effective means is provided for solving the unsatisfied clinical demand of the renal toxicity of the tacrolimus after the transplantation operation.

The present invention discloses an active exosome scaffold coating based on traditional Chinese medicine enhanced secretion, its preparation method and application, belonging to the technical field of biomedicine and interventional devices. The scaffold coating of the present invention includes: exosomes, including cardiomyocyte active exosomes and human mesenchymal stem cell active exosomes enhanced by traditional Chinese medicine; wherein, the traditional Chinese medicine includes: placenta extract, pilose antler extract, sheep myocardial peptide, sea cucumber peptide, black wolfberry peptide, osthole, curculigo rhizome extract, and morinda officinalis extract; the intervention concentration of each component added to the cells is 2-50 μg / mL; a photocurable gel matrix, including methacrylated gelatin, a photoinitiator, and polyether 127; tacrolimus; the final concentration of exosomes is 1×10 9 ~12×10 9 particles / mL, and the final concentration of tacrolimus is 5-25 μg / mL. This coating can be coated on the surface of a poly-L-lactic acid degradable stent to prepare a degradable stent, which has obvious ability to promote blood vessel repair.

The invention discloses an ophthalmic micro-emulsion preparation of tacrolimus, an ophthalmic in-situ gel preparation of tacrolimus as well as a preparation method and application of the ophthalmic micro-emulsion preparation and the ophthalmic in-situ gel preparation of tacrolimus. The tacrolimus eye micro-emulsion preparation comprises tacrolimus, a solubilizer and water, and the solubilizer comprises stearic acid polyethylene glycol ester and caprylic / capric acid polyethylene glycol glyceride. The tacrolimus ophthalmic in-situ gel preparation is prepared from tacrolimus, a solubilizer, a gel matrix and water. The tacrolimus ophthalmic microemulsion preparation and the tacrolimus ophthalmic in-situ gel preparation both can improve the drug loading capacity of tacrolimus, so that the effective drug amount acting on an affected part is improved; according to the tacrolimus eye microemulsion preparation, the solubility of tacrolimus can be remarkably improved, and eye medicine absorption can be promoted; according to the tacrolimus ophthalmic in-situ gel preparation, the retention time of eyes can be prolonged, and the bioavailability can be effectively improved.

The present application relates to the technical field of pharmaceutical analysis, and in particular to a combined analysis method for exploring the effect of Huangkui capsules on improving chronic kidney injury of tacrolimus based on metabolomics and proteomics. The combined analysis method of the present application explores how Huangkui capsules improve the mechanism of chronic kidney injury of tacrolimus from multiple dimensions, which is beneficial to in-depth analysis of the specific effects of Huangkui capsules at the molecular, cellular and tissue levels, reveals the key path and regulation mechanism of kidney protection, and can also provide a scientific basis for optimizing clinical application, further promoting the modernization of traditional Chinese medicine and its wide application in the treatment of kidney disease.

The present invention includes compositions and methods for making and using a rapid dissolving, high potency, substantially amorphous nanostructured aggregate for pulmonary delivery of tacrolimus and a stabilizer matrix comprising, optionally, a polymeric or non-polymeric surfactant, a polymeric or non-polymeric saccharide or both, wherein the aggregate comprises a surface area greater than 5 m2 / g as measured by BET analysis and exhibiting supersaturation for at least 0.5 hours when 11-15-times the aqueous crystalline solubility of tacrolimus is added to simulated lung fluid.

A cobalt-chromium alloy stent comprising several main body units, wherein each main body unit is composed of several supporting rings connected by flexible ribs and the adjacent main body units are connected by several connecting ribs. A drug eluting stent comprising the cobalt-chromium alloy stent and a drug coating containing arsenic trioxide and tacrolimus. The drug release curves of the two composite drugs of arsenic trioxide and tacrolimus used in the present invention are adjusted, so that the inflammatory response of vascular endothelial cells and the proliferation behavior of vascular smooth muscle cells are effectively inhibited, and the vascular restenosis rate is reduced.

The invention discloses a preparation method of tacrolimus capsules, and relates to the technical field of medicines. The preparation method comprises the following steps: S1, preparing a drug-loaded pellet core; s2, coating and curing a flexible buffer layer, namely curing for 8 hours under the conditions that the temperature is 100 DEG C and the relative humidity is 35%, so that the xanthan gum is in a swelling state; s3, coating with a high-barrier layer; s4, protective controlled release layer coating: preparing a coating solution from the third polymer grafted with the lipophilic bile salt derivative and phospholipid; and S5, capsule filling. Through functional gradient multilayer structure design and fine regulation and control of phospholipid composition and spatial distribution, multiple technical problems of poor chemical stability of tacrolimus, brittle rupture of a coating, burst drug release, dissolution and absorption disorder and release drift caused by individual difference of gastric emptying are synergistically solved; the excellent mechanical strength, stable and controllable release kinetics and obvious solubilization promoting effect of the pellet are realized. The method is clear in technological parameters and suitable for industrial production.

The invention discloses a tacrolimus-containing pellet pharmaceutical composition, the pharmaceutical composition is composed of an enteric pellet and a sustained-release pellet, the enteric pellet comprises 0.5-5% of tacrolimus, 10-80% of a filler, 2-10% of a disintegrating agent, 1-5% of an adhesive, 0.5-2% of a flow aid, 0.5-1% of a lubricant, and 5-13% of an enteric coating material; the sustained-release pellet comprises 0.5 to 2% of tacrolimus, 10 to 80% of a filling agent, 2 to 10% of a disintegrating agent, 1 to 5% of an adhesive, 0.1 to 1% of a flow aid, 0.1 to 1% of a lubricant, 5 to 15% of a sustained-release coating material and 0.1 to 0.5% of a plasticizer. The pellet pharmaceutical composition containing tacrolimus disclosed by the invention can maintain longer blood concentration and longer action time, so that the medicine taking frequency is reduced, the compliance of a patient is improved, the toxic and side effects are reduced, and the effectiveness and safety of medicine use are further ensured.

The invention relates to a nano antibody for specifically recognizing a tacrolimus-antibody compound and application of the nano antibody, and belongs to the technical field of biological detection. A variable region of the nano antibody has three complementary determining regions CDR1, CDR2 and CDR3, can specifically recognize a tacrolimus-antibody compound, and can be used for detecting drugs by a double-antibody sandwich method; the kit is widely suitable for various immunodetection technologies such as an enzyme-linked immunosorbent assay (ELISA), a chemiluminescence immunoassay (CLIA), an electrochemical luminescence immunoassay (ECLIA), a fluorescence immunoassay (FIA), an immunochromatography test strip method and the like. According to the method, the limitation of a traditional competition method is overcome, high-sensitivity, high-specificity and high-stability detection is realized, the method can be adapted to various detection platforms, and a portable pretreatment process without centrifugation can also be realized.

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 invention discloses an immunosuppressant transdermal patch and a preparation method thereof, the transdermal patch is provided with a backing layer, an ointment-containing body and a protective layer, the backing layer is a polyester and ethylene-vinyl acetate copolymer film, the ointment-containing body is formed by mixing a main drug tacrolimus, a stabilizer, a matrix, a cross-linking agent and a pressure-sensitive adhesive, and the protective layer is a polyester and ethylene-vinyl acetate copolymer film. The protective layer is a polyethylene glycol terephthalate film, the protective layer is coated with the ointment-containing body, and then the backing layer is pressed and covered on the surface of the ointment-containing body. The immunosuppressant transdermal patch provided by the invention can be adhered to parts such as neck, shoulder, chest, arm memory and the like, can be freely adjusted in use duration according to different illness states, and is safe and free of toxic and side effects. In addition, the transdermal patch disclosed by the invention is good in stickiness, good in permeability, free of irritation and allergy phenomena, good in patient compliance and capable of being used for a long time. Meanwhile, the method has the advantages of low preparation cost, simple and reasonable preparation process and the like, and has wide application prospects.

The present invention relates to the technical field of pharmaceutical engineering, and specifically relates to a preparation method of tacrolimus position isomers. By introducing the catalyst tetrakis(triphenylphosphine)palladium during the reaction process, it is possible to prepare tacrolimus position isomers with relatively high purity on the basis of reducing the reaction temperature. Compared with the prior art, it has the technical advantage of low-temperature reaction, resulting in the technical effects of reducing side reactions in the overall reaction, lowering the purification difficulty, and increasing the product yield.

The application belongs to the technical field of medicines, and discloses a tacrolimus microcrystal and a preparation method and application thereof. Compared with the raw medicine, the tacrolimus microcrystal has a significantly improved dissolution rate, cumulative dissolution rate, hydrophobicity and safety (non-irritation). Compared with the existing medicine preparation, the tacrolimus microcrystal has the advantages of long retention time and better treatment effect.

The present disclosure relates to methods for the treatment of diseases or disorders (e.g., cancer) with mTOR inhibitors. Specifically, the disclosure relates to methods of treating a subject having a cancer by administering a particular dosage of an mTOR inhibitor. In some embodiments this disclosure includes methods for delaying, preventing, or treating acquired resistance to RAS inhibitors using a dosage of an mTOR inhibitor. In some embodiments, this disclosure relates to methods of treating or preventing adverse events associated with administration of an mTOR inhibitor using tacrolimus.

The invention discloses a tacrolimus personalized medication guiding gene CYP3A5 * 3 polymorphic site detection kit and a use method thereof, the kit utilizes an MGB probe and the energy difference of different polymorphic bases to directly judge the polymorphism of the gene through an amplification curve, and calculation and sequencing analysis are not needed. The kit comprises a pair of primers and a probe which are used for amplifying CYP3A5 * 3 polymorphic sites, the kit further comprises positive samples of three polymorphisms of CYP3A5 * 3CC, CT and TT. The CYP3A5 * 3 typing related sites can be rapidly detected, the sensitivity, specificity and accuracy are superior to those of a first-generation sequencing and double-probe calculation method, rapid and accurate information is provided for individualized drug administration of clinical transplantation patients, and rejection and other side effects after drug administration are avoided.

: The present invention provides a topical pharmaceutical composition comprising Janus kinase (JAK) inhibitors like Tofacitinib, Immunosuppressive agent like Tacrolimus, Fingolimod and statins like atorvastatin, Simvastatin, Fluvastatin, Lovastatin, Pitavastatin, Pravastatin and Rosuvastatin dissolved or dispersed in a pharmaceutically acceptable base together with other pharmaceutically acceptable excipients or in a dermatologically acceptable carrier, useful in the treatment of vitiligo. The inventive concept provided herein are methods and pharmaceutical compositions by preparing oral dosage forms like Topical liquid spray or Topical cream or Topical gel dosage form for the management of vitiligo and its associated disorders and accordingly performing preclinical study to prove the efficacy of the selected drug substances from the class of JAK inhibitors, statins and immunosuppressants.

The invention discloses application of tacrolimus in preparation of a medicine for treating type 2 diabetes and complications thereof, and belongs to the field of biological medicine. Animal experiments prove that Tacrolimus (TM) can effectively improve type 2 diabetes mellitus and obesity-related abnormal glycolipid metabolism. In addition, the TM can also relieve liver injury caused by diabetes and obesity and improve liver fatty degeneration and abnormal lipid metabolism. What's more important is that toxicity of TM to pancreatic beta cells is not observed in long-term multi-model experiments (including diabetes, obesity and elderly mice). The invention provides an important basis for developing novel diabetes treatment drugs, lays a foundation for expanding new indications of tacrolimus, and has potential clinical transformation value.

The invention discloses a fibroblast composite bone filling preparation as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The method comprises the following steps: specifically culturing fibroblasts by using Yoda1 and matrix I-type collagen, and activating the osteogenic differentiation capability of the fibroblasts; resuspending the finished product fibroblasts capable of activating the osteogenic differentiation capacity in a solution containing ginsenoside, tacrolimus and fibronectin to obtain a mixed solution; and finally, mixing the mixed solution with the bone filler to obtain the fibroblast composite bone filling preparation capable of promoting repair. The preparation can provide fibrosis support and promote vertebra fusion, does not cause inflammatory reaction, and has a large-scale application prospect.

The invention relates to a tacrolimus-loaded nano material as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The invention provides a preparation method of a tacrolimus-loaded nano material, which comprises the following steps: dispersing MnO2 nanosheets in water, carrying out ultrasonic treatment, and centrifuging to obtain a supernatant; mixing the supernate with dopamine hydrochloride, adjusting the pH value, stirring, centrifuging to obtain supernate, and dialyzing to obtain MnO2 / PDA NPs; and mixing a tacrolimus chloroform solution with the obtained MnO2 / PDA NPs, centrifugally collecting the precipitate, and washing to obtain the nano material loaded with tacrolimus. According to the method, MnO2 is subjected to ultrasonic treatment and then centrifuged, MnO2 / PDA NPs containing polydopamine is prepared from MnO2 and dopamine hydrochloride, polydopamine serves as a functional medium, tacrolimus is effectively loaded on a MnO2 substrate through coordination self-assembly, and the nano material loaded with tacrolimus is successfully synthesized.

The invention relates to the technical field of medicines, in particular to application of a flavonoid metabolite for improving tacrolimus-induced chronic renal injury. The invention provides application of a flavonoid metabolite, namely quercetin-7-O-beta-glucuronide, in an abelmoschus esculentus capsule to improvement of chronic renal injury induced by tacrolimus, and particularly provides application of the flavonoid metabolite, namely quercetin-7-O-beta-glucuronide in the abelmoschus esculentus capsule. The research shows that the quincetin-7-O-beta-glucuronide has relatively strong biological activities of resisting inflammation, resisting oxidation, resisting fibrosis and the like, and plays an important role in preventing and treating the chronic renal injury caused by tacrolimus.

The invention relates to an anti-immunological rejection FK506 (at) ZIF-8 / HTCC ophthalmic gel and a preparation method thereof, FK506 and a zeolite imidazole skeleton (ZIF-8) are combined to prepare FK506 loaded nanoparticles (FK506 (at) ZIF-8), and quaternized chitosan is innovatively used as a sol of the FK506 (at) ZIF-8 to prepare the ophthalmic gel for use. The problems that a novel potent immune preparation tacrolimus administration mode is short in drug retention time, fast in metabolism, poor in cornea permeability and insoluble in water, and consequently the bioavailability of the FK506 eye drops is low are solved. Compared with an FK506 direct administration mode, the administration mode of the novel nanoparticle drug-loaded ophthalmic gel is higher in drug utilization rate, has a treatment effect on corneal transplantation immunological rejection, and delays the occurrence and development of transplantation rejection.