45 results about "Bisphosphonate" patented technology

Provided herein are method of treating retinal disease using a bisphosphonate acid sphingomyelinase (ASM) and farnesyl diphosphate synthase (FDPS) inhibitor, such as zoledronic acid, at low doses.

The present invention aims to provide a pyrrolyl-based carbazole bisphosphonate polymer, a synthesis method therefor, and the use thereof. In the polymer, a conjugated structure is formed by linking two carbazole molecules via a pyrrole ring, and therefore the carrier transport efficiency when the material is applied to hole transport layers is ensured, the dipole moment of the molecule and the properties of an interface are well regulated, and the wettability and coverage effect with substrates are improved. Battery structures prepared by using the material have higher photoelectric conversion efficiency and stability.

The application belongs to the technical field of bioactive nanomaterials, and particularly relates to a metformin nanomaterial, a preparation method and application thereof. The average hydrodynamic diameter of the nanomaterial is less than 500 nm, and the nanomaterial is prepared by a preparation method comprising the following steps: self-assembly of metformin and polyphenols to obtain metformin-polyphenol nanoparticles; reaction of bisphosphonate and polyethylene glycol to obtain bisphosphonate-polyethylene glycol organic segments; and reaction of the metformin-polyphenol nanoparticles and the bisphosphonate-polyethylene glycol organic segments to obtain the nanomaterial. The metformin, polyphenol, polyethylene glycol and bisphosphonate are prepared into the metformin-loaded nanomaterial through specific reactions, the systemic delivery of metformin is realized, the efficacy and bioavailability of metformin on osteoporosis are improved, and the bone targeting of metformin is also improved.

The present invention relates to a large scale GMP synthesis method of a modified glucan conjugate, and more particularly, to a glucan-guanidine-bisphosphonate conjugate wherein the bisphosphonate is an alendronate group. The large-scale GMP synthesis method related to the invention can be used for producing the glucan-guanidine-bisphosphonate conjugate with high purity and medicinal grade. The invention also relates to an application of the glucan-guanidine-bisphosphonate conjugate in a medicine for treating tumors.

This invention discloses a preparation method and application of a lauryl bisphosphonate / mesoporous hydroxyapatite organic-inorganic hybrid composite material, belonging to the field of landfill leachate treatment technology. A solution of dipotassium hydrogen phosphate is prepared and then added dropwise to a mixed solution of calcium chloride and lauryl bisphosphonate. The pH of the solution is adjusted with alkali, washed with water, and then heated and dried to obtain the lauryl bisphosphonate / mesoporous hydroxyapatite organic-inorganic hybrid composite material. This composite material exhibits strong complexing ability with various heavy metal ions, and its adsorption performance is minimally affected by soluble organic acids in landfill leachate, ensuring long-term locking of heavy metal ions and avoiding secondary pollution caused by the re-dissolution of heavy metals. It has strong market potential and application value in the fields of landfill leachate treatment and environmental remediation.

The present application relates to the technical field of plant protection, and particularly relates to a chestnut blight prevention and treatment method based on mixing of an ethoprop aluminum-containing immune activator and a biocontrol bacterial fermentation filtrate. The technical scheme comprises the following steps: preparing PDA culture mediums containing different concentrations of ethoprop aluminum and different dilution multiples of a B. badius B268 fermentation filtrate, transferring a bacterial cake for culture, performing indoor toxicity determination, selecting chestnut saplings, setting three treatment groups and two control groups, collecting leaf blades before spraying of the pesticide for storage, and using the leaf blades for subsequent enzyme activity analysis and MDA content determination, determining a spraying concentration according to the toxicity test result, spraying the treatment groups of the chestnut saplings, mixing the ethoprop aluminum and the B268 fermentation filtrate in the treatment group, and then performing inoculation experiments, collecting leaf blade samples periodically after inoculation for subsequent enzyme activity analysis and MDA content determination, and performing transcriptome sequencing. The present application can improve the bacteriostatic capacity of the prevention and treatment pesticide, activate the plant's own immune function, and reduce the amount of chemical pesticide application.

The application provides an immune cell culture kit, a culture method and application of gamma delta T cells, and the kit comprises a basic culture medium, a recombinant antibody, a cytokine and a cell proliferation promoting additive, the basic culture medium comprises an RPMI-1640 culture medium, and the cell proliferation promoting additive comprises 1-thioglycerol, taurine, beta-cyclodextrin, thymidine, alpha-lipoic acid, beta-mercaptoethanol and bisphosphonate. The gamma delta T cells obtained by the culture kit have high purity and activity, and have good tumor killing activity. The gamma delta T cells obtained by the method have a high positive rate of 100% of perforin expression.

The present invention provides: a method for preparing tissue-targeting nanoparticles, the method comprising a step for generating phospholipid nanoparticles, a step for generating mesenchymal stem cell-derived cell membrane nanoparticles, and a step for fusing the generated phospholipid nanoparticles and cell membrane nanoparticles to generate tissue-targeting nanoparticles; and tissue-targeting nanoparticles which are prepared by the method and comprise bisphosphonate-containing phospholipid nanoparticles and mesenchymal stem cell-derived cell membrane nanoparticles.

This invention discloses a bisphosphonate-nucleic acid nanoparticle, its preparation method, and its applications. The preparation method involves adding divalent metal ions to a rolling circle amplification (RoBA) reaction solution, followed by the addition of bisphosphonate, to perform a RoBA reaction to obtain the bisphosphonate-nucleic acid nanoparticles. The RoBA reaction solution contains a circular DNA template. The preparation method of this invention has the advantages of high speed, precise synthesis, and simplicity, realizing multiple reactions—RoBA, ion coordination, crystallization, and co-assembly of DNA and bisphosphonate—in the same reaction system, greatly simplifying the reaction process and improving reaction efficiency. The obtained bisphosphonate-nucleic acid nanoparticles exhibit dual-pathway therapeutic effects and excellent ribozyme stability, showing promising application prospects.

The invention belongs to the technical field of bioactive nano materials, and particularly relates to a metformin nano material as well as a preparation method and application thereof. The average hydrodynamic diameter of the nano material is less than 500 nm, and the nano material is prepared by the preparation method comprising the following steps: self-assembling metformin and a polyphenol compound to obtain metformin-polyphenol nano particles; the preparation method comprises the following steps: reacting bisphosphonate with polyethylene glycol to obtain a bisphosphonate-polyethylene glycol organic chain segment; the metformin-polyphenol nano particles and the diphosphonate-polyethylene glycol organic chain segment are subjected to a reaction, and the nano material is obtained. According to the invention, the metformin, the polyphenol, the polyethylene glycol and the bisphosphonate are subjected to a specific reaction to prepare the metformin-loaded nano material, so that the whole-body delivery of the metformin can be realized, the curative effect and bioavailability of the metformin on osteoporosis are improved, and meanwhile, the bone targeting property of the metformin is improved.

The invention discloses application of Crlf2 in preparation of a medicine for preventing, relieving and / or treating osteoporosis, and relates to the technical field of new application of medicines. According to the application of the Crlf2 in preparation of the medicine for preventing, relieving and / or treating the osteoporosis, the key regulation and control function of the Crlf2 in differentiation of bone tissue related cells and osteoporosis diseases is disclosed for the first time, and a new theoretical perspective is provided for pathogenesis of the osteoporosis; it is found that the Crlf 2 inhibitor (such as a specific antibody or a small molecule inhibitor) can be directly used for preparing the efficient and high-targeting anti-osteoporosis medicine, the limitation of existing treatment means (such as bisphosphonate medicine inhibiting bone resorption but not promoting bone formation) is broken through, and accurate intervention aiming at a specific signal channel is achieved.

Methods of treating osteonecrosis in a subject are provided. In some embodiments, the method comprises administering to a subject having or suspected of having osteonecrosis a pharmaceutical composition comprising a conjugate of an LLP2A peptidomimetic ligand and a bisphosphonate drug. In some embodiments, the pharmaceutical composition comprises a conjugate of LLP2A and alendronate (LLP2A-Ale). In some embodiments, the method further comprises administering exogenous mesenchymal stem cells.

The invention discloses bionic sugar polypeptide hydrogel with sugar modification combined with bisphosphonate-metal ion coordination as well as a preparation method and application of the bionic sugar polypeptide hydrogel, and belongs to the field of biomedical materials. The hydrogel comprises polypeptide modified by bisphosphonate and dopamine, polypeptide modified by bisphosphonate and glycosyl and a metal ion solution, and the preparation method comprises the following steps: carrying out amidation reaction on alendronate sodium, dopamine hydrochloride or adipic dihydrazide and polypeptide in a water solution, dialyzing, and drying to obtain the hydrogel. The polypeptide modified by the bisphosphonate and the dopamine or the polypeptide modified by the bisphosphonate and the hydrazide is obtained; wherein the bisphosphonate and hydrazide modified polypeptide are dissolved in an aqueous solution, monosaccharide is added for reaction and dialysis to obtain bisphosphonate and glycosyl modified polypeptide, the bisphosphonate and glycosyl modified polypeptide is blended with bisphosphonate and dopamine modified polypeptide, a metal ion solution is added for uniform mixing to obtain the bionic glycopolypeptide hydrogel, and the bionic glycopolypeptide hydrogel is used for preparing drugs or medical products for promoting wound healing of diabetes mellitus. The important clinical application value is realized.

To provide methods of treating osteonecrosis in a subject.SOLUTION: In some embodiments, the method comprises administering to a subject having or suspected of having osteonecrosis a pharmaceutical composition comprising a conjugate of an LLP2A peptidomimetic ligand and a bisphosphonate drug. In some embodiments, the pharmaceutical composition comprises a conjugate of LLP2A and alendronate (LLP2A-Ale). In some embodiments, the method further comprises administering exogenous mesenchymal stem cells.SELECTED DRAWING: Figure 2

Compounds containing polymer material and a phosphorous flame protection agent on the basis of an aminomethyl bisphosphonate, a method for manufacturing the compound, the use of the flame retardant, and selected structures of the flame retardant are disclosed.

The present invention provides methods of treating a subject having a primary inflammatory disease or disorder comprising administering to the subject a composition comprising a conjugate of an LLP2A peptidomimetic ligand and a bisphosphonate drug, wherein the composition comprising the LLP2A-bisphosphonate conjugate enhances the delivery of mesenchymal stem cells to a site of inflammation. Methods of enhancing an anti-inflammatory or immunomodulatory property of mesenchymal stem cells, comprising administering to a subject in need thereof the mesenchymal stem cells and a composition comprising a conjugate of an LLP2A peptidomimetic ligand and a bisphosphonate drug, are also provided.

The invention provides a preparation method of polymethyl methacrylate / hydroxyapatite with a lasting antibacterial function, which means that silver bisphosphonate containing unsaturated quaternary ammonium cations or copper bisphosphonate containing unsaturated quaternary ammonium cations is deposited on the surface of hydroxyapatite to prepare antibacterial hydroxyapatite with polymerization reaction characteristics. And the polymethyl methacrylate participates in a polymerization reaction of methyl methacrylate to prepare composite material micro powder with the hydroxyapatite surface grafted with polymethyl methacrylate. The polymethyl methacrylate / hydroxyapatite composite material micro powder has antibacterial and bacteriostatic performance, medical efficacy of diphosphonate, water absorption performance in a medium and biocompatibility performance, and can improve the binding force and dispersity of hydroxyapatite and polymethyl methacrylate; further, the tensile strength, the bending strength and the compressive strength of the polymethyl methacrylate-based bone cement are improved; the addition amount of hydroxyapatite in the polymethyl methacrylate-based bone cement is increased, so that the curing thermal effect and the curing shrinkage of the polymethyl methacrylate-based bone cement are reduced.

The invention provides a method for modifying hydroxyapatite with calcium bisphosphonate containing unsaturated quaternary ammonium cations, and the hydroxyapatite modified with calcium bisphosphonate containing unsaturated quaternary ammonium cations can participate in polymerization reaction of methyl methacrylate to prepare functional polymethyl methacrylate micro powder. Therefore, the polymethyl methacrylate is endowed with antibacterial and bacteriostatic performance, medical efficacy of the bisphosphonate, water absorption performance in a medium and biocompatibility, and meanwhile, the binding force and dispersity of the hydroxyapatite and the polymethyl methacrylate can be improved; further, the tensile strength, the bending strength and the compressive strength of the polymethyl methacrylate-based bone cement are improved; the addition amount of hydroxyapatite in the polymethyl methacrylate-based bone cement is increased, so that the curing thermal effect and the curing shrinkage of the polymethyl methacrylate-based bone cement are reduced.

The application discloses an anti-inflammatory hydrogel as well as a preparation method and application thereof; the anti-inflammatory hydrogel is obtained by cross-linking four-arm polyethylene glycol thiol, eight-arm polyethylene glycol maleimide and metal coordination nanoparticles in a PBS buffer solution; the metal coordination nanoparticles are modified with diphosphonate, minocycline hydrochloride and Mg 2+ The metal coordination is composed of magnesium ions, phenolic hydroxyl groups on the minocycline hydrochloride and diphosphonate groups on the diphosphonate. The anti-inflammatory hydrogel has the performances of responding to a spinal cord injury microenvironment, releasing the anti-inflammatory drug minocycline hydrochloride, inhibiting the polarization of macrophages / microglia to M1 type and the like, can better play the drug effect of anti-inflammation and promoting spinal cord injury repair, has the advantages of convenient operation, no harmful by-products and the like, and has a wide application prospect.

Provided is a method of generating iPS cells. Specifically, provided is a method of generating iPS cells having a rearranged γδ-TCR gene. Also provided is a cell population including the generated iPS cells. The method includes stimulating collected blood cells with IL-2 and a bisphosphonate, and then introducing cell reprogramming factors through use of a Sendai virus (SeV) vector. According to the method of the present invention, iPS cells having a rearranged γδ-TCR gene can be effectively generated. In particular, the method may be free of a step of treating the blood cells with an antibody before the step of stimulating blood cells with any one kind or a plurality of kinds of interleukins selected from IL-2, IL-15, and IL-23, and a bisphosphonate. In addition, iPS cells generated by the method of the present invention can be differentiated into desired cells by differentiation induction treatment.

This invention relates to the field of polyurethane technology and discloses a waterborne polyurethane fire-retardant coating and its preparation method. A novel carboxyl-containing waterborne flame-retardant chain extender is prepared using pentaerythritol diphosphate bisphosphonate chloride, 4-methoxy-L-phenylalanine, and pyridine hydrochloride as reactants. This chain extender is then polymerized with diol and diisocyanate monomers to obtain the waterborne polyurethane fire-retardant coating. The waterborne polyurethane emulsion exhibits good dispersibility, high emulsion stability, and excellent hardness. Furthermore, the nitrogen-phosphorus flame-retardant structure of bisspirocyclic phosphoramide is grafted into the polyurethane molecular chain, significantly improving the limiting oxygen index of the polyurethane film material to 27.9-29.6%, achieving a UL-94 rating of V-0.

The invention is directed to a method of inhibiting bone resorption. The method comprises administering to a human an amount of sclerostin inhibitor that reduces a bone resorption marker level for at least 2 weeks. The invention also provides a method of monitoring anti-sclerostin therapy comprising measuring one or more bone resorption marker levels, administering a sclerostin binding agent, then measuring the bone resorption marker levels. Also provided is a method of increasing bone mineral density; a method of ameliorating the effects of an osteoclast-related disorder; a method of treating a bone-related disorder by maintaining bone density; and a method of treating a bone-related disorder in a human suffering from or at risk of hypocalcemia or hypercalcemia, a human in which treatment with a parathyroid hormone or analog thereof is contraindicated, or a human in which treatment with a bisphosphonate is contraindicated.

According to the present disclosure, a method for producing stem cells is provided, comprising applying tetrakis-pivaloyloxymethyl 2-(thiazol-2-ylamino) ethylidene-1, 1-bisphosphonate (PTA) to blood cells or immune cells, and inducing stem cells from said blood cells or immune cells.

The invention belongs to the technical field of biomedical materials, and particularly relates to a preparation method and application of ionic cross-linked sodium hyaluronate gel, and the preparation method comprises the following steps: S1, dissolving sodium hyaluronate powder, carrying out carboxyl activation, adding an amino-containing bisphosphonate compound, and carrying out amidation reaction to obtain a sodium hyaluronate solution; a sodium hyaluronate polymer solution modified by diphosphonic acid groups is obtained; s2, dialyzing and washing the sodium hyaluronate polymer solution obtained in the step S1 by using a dialysis bag, and freeze-drying to obtain the diphosphonic acid group modified sodium hyaluronate freeze-dried sponge, s3, dissolving the sodium hyaluronate freeze-dried sponge prepared in S2, and adjusting the pH value of the system to obtain a dissolved solution; s4, dissolving or dispersing a solid compound containing metal ions into the dissolving solution in S3, uniformly stirring and mixing, and standing for crosslinking; and S5, performing high-pressure steam sterilization on the hydrogel formed by crosslinking in the step S4 to obtain the medical sterile ionic crosslinking sodium hyaluronate gel.

Described herein, in some aspects, are bisphosphonate lipid compounds, lipid nanoparticles (LNPs) thereof, and methods of use thereof. In various embodiments, the LNP selectively targets a cell of interest (e.g., a bone cell and / or bone marrow cell, such as a stem cell, stroma cell, osteoblast, osteocyte, osteoclast, bone lining cell, local mesenchymal cell, progenitor cell, mononuclear blood-borne precursor cell, B cell, endothelial cell, granulocytes, T cell, monocytic lineage, B cell lineage, monocytes, cancer cell, tumor cell, tumor cell that metastasizes to bone, blood cancer cell, and multiple myeloma cell, inter alia). In other aspects, the present disclosure relates to methods for in vivo delivery of therapeutic agents to prevent or treat diseases, disorders, or conditions using the LNP compositions of the disclosure.

This invention belongs to the field of biomedical technology and discloses an antitumor composition and its application of an engineered bacterium expressing hemolysin and a bisphosphonate compound. The composition comprises an engineered bacterium that targets and colonizes tumors and secretes hemolysin, and a bisphosphonate compound. The engineered bacterium specifically induces tumor hemorrhage; the secreted hemolysin lyses red blood cells, which are then phagocytosed by macrophages. The hemolysin then self-assembles with the bisphosphonate compound intracellularly, generating a large amount of reactive oxygen species, thereby remodeling the antitumor phenotype of tumor-associated macrophages and achieving an antitumor effect. Furthermore, the engineered bacterium does not induce bleeding in normal blood vessels and therefore has no effect on normal cells.

The application relates to the field of animal model construction, in particular to a naked mole rat immunodeficiency animal model establishment method, which is established by regularly injecting a naked mole rat with a chloromethylene bisphosphonate-liposome, and the naked mole rat immunodeficiency animal model is established. The naked mole rat immunodeficiency animal model establishment method has the advantages of short cycle, simple operation, good reproducibility, remarkable immune intervention effect, and can be used for the research on the related functions of the naked mole rat macrophage action mechanism.

The invention provides a hafnium-based bisphosphonate aggregate hydrogel sustained-release system as well as a preparation method and application thereof, and belongs to the technical field of bioengineering and materials. The preparation method comprises the following steps: dropwise adding a hafnium tetrachloride solution into a mixed solution containing a bisphosphonate drug and a chemotherapeutic drug, carrying out liquid-liquid phase separation to obtain a reaction solution, carrying out stirring reaction, and centrifuging to obtain a precipitate, namely the hafnium-based bisphosphonate aggregate hydrogel sustained-release system. The invention also discloses the hafnium-based bisphosphonate aggregate hydrogel sustained-release system prepared by the preparation method, and also discloses application of the hafnium-based bisphosphonate aggregate hydrogel sustained-release system in preparation of a radiotherapy sensitizer for treating osteosarcoma and preparation of a drug delivery system. The hafnium-based bisphosphonate aggregate hydrogel sustained-release system prepared by the invention has the ideal characteristics of easiness in preparation, ultrahigh drug loading capacity, pH-dependent controlled release, 'fine adjustment 'release rate, avoidance of drug waste, improvement of treatment effect, control of adverse side effects and the like.

Disclosed is a hydrogel drug delivery composition comprising a therapeutic agent and a poloxamer, wherein the poloxamer is modified to be capable of adhering to a surface of bones or teeth, and wherein the poloxamer is modified by pyrophosphate, bisphosphonates, acidic peptides or tetracycline and its derivatives.