102 results about "Tacrolimus" patented technology

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.

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 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 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.

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 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 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.

The invention relates to the technical field of external ointment, in particular to compound external ointment for treating leukoplakia vulvae and a preparation method of the compound external ointment. 0.03 part of tacrolimus; 2.5 parts of hypocrellin; 5 parts of a cortex phellodendri extract; 10 parts of hyaluronic acid; 3 parts of vitamin E; and 70-75 parts of a matrix. Inflammation is rapidly controlled through low-efficiency glucocorticoid, local immune abnormality is inhibited through the immunomodulator, tissue is repaired through traditional Chinese medicine components, and bacteria are resisted, so that a quick-acting and long-acting combined mode is formed, hormone side effects are neutralized by adding hyaluronic acid and vitamin E, and the feasibility of the treatment course is prolonged; the total effective rate of the combined medicine for avoiding vitamin E oxidation through low-temperature mixing is remarkably higher than that of a traditional scheme, the occurrence rate of skin atrophy is reduced to 4% and far lower than 22% of that of the traditional scheme, and meanwhile, the staged mixing process ensures that the retention rate of active ingredients is larger than 95% and is remarkably superior to that of the traditional process.

The invention discloses application of naringenin in preparation of a medicine for preventing and treating cardiotoxicity induced by tacrolimus. The naringenin disclosed by the invention is a natural active matter, is non-toxic to cells, and has a potential heart protection effect of reversing, preventing and treating tacrolimus-induced cardiotoxicity; naringenin reduces expression of Cav1.2 on a membrane so as to influence a calcium signal channel and reverse calcium overload and cell apoptosis caused by tacrolimus; cav1.2 can be used as a target spot for preventing and treating cardiotoxicity induced by FK506, and the invention also prompts that overload calcium can be treated by using a corresponding calcium chelating agent, so that a theoretical basis is provided for the naringenin as a potential auxiliary medicine for tacrolimus application; the further deep research is expected to be beneficial to deep understanding of the action mechanism of the naringenin and provide more support for clinical application of the naringenin.

A degradable biomedical magnesium alloy drug-eluting vascular stent and a preparation method. With the total weight of a magnesium alloy being 100% for calculation, the magnesium alloy comprises the following components in percentage by weight: 3.0-6.0% of Gd, 2.5-5.5% of Y, 1.0-3.0% of Li, 0.3-1.0% of Zn, 0.2-1.0% of Zr, and the balance being Mg. The stent has good radial support strength and strain dispersion capability by means of finite element design. After a protective coating is used, the corrosion resistance of the magnesium alloy stent is greatly improved. An arsenic trioxide / rapamycin and tacrolimus composite drug sustained-release system is used to fully adapt to the damage repair process of blood vessels. An implantation result of large animals shows that the vascular stent system has a good anti-restenosis treatment effect.

The present invention relates to the field of medical technology, and specifically discloses a high-purity tacrolimus and a preparation method thereof. The present invention soaks the mycelium obtained by separating the tacrolimus fermentation broth in a short-chain alcohol solvent and a salt solution, preliminarily removes the pigment and other protein impurities contained in the mycelium, and then uses a nanofiltration concentrator with a cut-off molecular weight of 200Da-300Da to concentrate and remove ions and small molecular impurities, and then adds sodium dodecylbenzene sulfonate to the concentrated solution, changes the distribution ratio of tacrolimus and impurities in the mother liquor and crystals, increases the solubility of impurities in the mother liquor, makes tacrolimus fully crystallize and precipitate, further removes secondary metabolites generated in the fermentation process, improves the quality of the target product, and finally purifies and separates through a dynamic axial compression column, fully removes ascomycin and dihydrotacrolimus and other analog impurities, greatly improves the purity of tacrolimus, and finally obtains high-purity tacrolimus with a content of more than 99.98%.

Embodiments of the disclosure provide ophthalmic compositions and methods of use thereof. The embodiments disclose ophthalmic compositions including devices such as a punctal plug. Some embodiments are directed to a method of preparing and using such devices. One embodiment provides a method of dissolving a hydrophilic polymer and an active pharmaceutical ingredient (API) in alcohol to form a hydrophilic polymer / API solution, where the API includes tacrolimus, spray drying the hydrophilic polymer / API solution to form a hydrophilic polymer / API mixture, mixing the hydrophilic polymer / API mixture with a binder to form an API paste, and curing the API paste to form a punctal plug, where the punctal plug is configured to release an effective amount of the API for a treatment period of 30 days to one year.

This invention relates to a chemiluminescent immunoassay reagent for tacrolimus, its preparation, and detection method. The reagent comprises a first reagent, a second reagent, and a magnetic separation reagent. The first reagent is a buffer solution containing a fluorescein-labeled anti-tacrolimus monoclonal antibody at a pH of 6.0–9.0, with the concentration of the fluorescein-labeled anti-tacrolimus monoclonal antibody being 1.0–5.0 μg / mL. The second reagent is a buffer solution containing a tacrolimus-alkaline phosphatase conjugate at a pH of 6.0–9.0, with the concentration of the tacrolimus-alkaline phosphatase conjugate being 0.05–0.20 μg / mL. The magnetic separation reagent is a suspension of magnetic microparticles coated with the anti-fluorescein monoclonal antibody. This invention enables the quantitative detection of tacrolimus with lower cost and higher accuracy and precision.

A long acting injectable formulation based on combination of biodegradable poly(D,L-lactide-co-glycolide) microparticles comprising different PLGA polymers and Tacrolimus. The microparticles may include Tacrolimus, a first polymer and a second polymer, and the first and second polymer may differ from each other. Each of the first and second polymers may be a poly(D,L-lactide-co-glycolide) polymer. Each of the first and second polymers may have an identical lactide to glycolide ratio. Each of the first and second polymers may have a different molecular weight

The present invention relates to a method for preparing high-purity tacrolimus by removing, from a lactone compound having an unsaturated alkyl group, particularly a tacrolimus (FK506) workpiece, impurities having similar chemical structures thereto but not having an unsaturated alkyl group, particularly ascomycin (FK520) and a propyl analog of tacrolimus. More specifically, provided is an economical purification method enabling the recovery of high-purity tacrolimus in high yield by dissolving the tacrolimus workpiece in an aqueous silver ion solution, and then, by using a small amount of an adsorption resin, removing similar impurities which do not bind to the silver ions.