35 results about "Zoledronic acid" patented technology

The invention discloses an artificial bone for promoting osteoporotic bone defect repair and a preparation method thereof, and belongs to the technical field of biomedical materials. The artificial bone disclosed by the invention is prepared by compounding the following components in percentage by weight: 89.65 to 89.85 weight percent of polylactic acid-glycolic acid copolymer, 9.85 to 10.15 weight percent of nano hydroxyapatite and 0.1 to 0.5 weight percent of zoledronic acid. In the artificial bone, the nano-hydroxyapatite and zoledronic acid are uniformly dispersed in the polylactic acid-glycolic acid copolymer, and the porous structure on the surface of the artificial bone is combined, so that osteoblasts can be attached to the surface of the artificial bone, and new bone tissues can grow in the artificial bone; phosphonate radicals of zoledronic acid can be chelated with nano-hydroxyapatite to generate stable chemical bonds, the stable chemical bonds are introduced into the polylactic acid-glycolic acid copolymer, effective loading of zoledronic acid can be achieved, and the effective loading of zoledronic acid can inhibit bone resorption increase caused by overactivation of osteoclasts and repair osteoporotic bone defects.

The invention relates to the technical field of biological medicine, in particular to a cell culture medium and a preparation method of gamma delta T cells. The cell culture medium is a culture medium A or a culture medium B. The culture medium A comprises a serum-free culture medium, 1-100 [mu] M of zoledronic acid, 50-500 U / mL of IL-2, 1-5 [mu] M of imiquimod, 1-20 ng / mL of IL-15, 1-50 ng / mL of IL-1b, 10-100 ng / mL of IL-7 and 2-10% (v / v) of inactivated plasma or a serum substitute. The culture medium B comprises a serum-free culture medium, 100 to 2000 U / mL of IL-2, 1 to 50 ng / mL of IL-15, 1 to 10 [mu] M of zoledronic acid and 2 to 10% (v / v) of inactivated plasma or a serum substitute. By adopting the cell culture medium, a large number of gamma delta T cells can be rapidly obtained.

The invention provides a gamma delta T cell culture method and a culture medium, and belongs to the technical field of T cell culture. Modified nanoparticles, zoledronic acid, vitamin C and glutamine are added into a 1640 culture solution, the concentration of the modified nanoparticles ranges from 0.5 g / L to 1 g / L, the concentration of the zoledronic acid ranges from 0.5 mu mol / L to 1.5 mu mol / L, the concentration of the vitamin C ranges from 200 mu mol / L to 500 mu mol / L, and the concentration of the glutamine ranges from 0.1 mmol / L to 0.2 mmol / L. The prepared culture medium can efficiently stimulate amplification of the gamma delta T cells and improve the killing activity of the gamma delta T cells, meanwhile, the survival rate of the gamma delta T cells is also improved, and meanwhile, the culture method of the gamma delta T cells is simple, low in cost and wide in application prospect.

Disclosed is a zinc zoledronate micro-nanoparticle adjuvant, which contains zinc and zoledronic acid and optionally contains a phosphate and aluminum. The preparation method therefor comprises performing mixed precipitation on a soluble salt solution containing zinc ions, zoledronic acid, and sodium hydroxide. The adjuvant can be used to prepare vaccines, etc.

The invention discloses an NKT cell in-vitro amplification method based on a combined stimulant, and belongs to the technical field of biology. The method comprises the following steps: firstly separating mononuclear cells in autologous peripheral blood, and then performing induced activation and amplification on the NKT cells in a serum-free culture system by adding a group A streptococcus preparation, a zoledronic acid preparation and a cytokine IL-2 as a combined stimulant. The method is easy to operate, efficient amplification of the NKT cells can be achieved only through three key reagents, the obtained NKT cells have the advantages of being large in number, high in purity, high in cytotoxicity and the like, and the requirements of clinical treatment can be met. Compared with a traditional method, the culture cost is remarkably reduced, the operation process is simplified, large-scale production, popularization and application are easy, and an efficient and economical technical scheme is provided for NKT cellular immunotherapy.

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 invention relates to the field of high polymer materials and medical engineering, in particular to a high polymer nanoparticle with bone targeting, acid environment neutralization and oxidation resistance characteristics and a preparation method of the high polymer nanoparticle. The polymer nanoparticle is prepared from the following raw materials: a zoledronic acid modified polycaprolactone-polypeptide copolymer, the chemical structural formula of the copolymer is as follows: # imgabs0. The polymer nanoparticles prepared by taking the zoledronic acid modified polycaprolactone-polypeptide copolymer as a raw material have the advantages of bone targeting, excellent oxidation resistance and capability of neutralizing an acid environment. The polymer nanoparticles can exert significant efficacy (oxidation resistance and acid environment neutralization) for treating osteoporosis only by means of intrinsic activity of the materials of the polymer nanoparticles, so that a series of toxicity problems possibly caused by traditional drugs are substantially reduced fundamentally, and a brand new scheme is provided for treatment of osteoporosis.

The present application relates to the field of high polymer material and medical engineering, and particularly relates to a high polymer nanoparticle with bone targeting, neutralizing acidic environment and antioxidant properties and a preparation method thereof. The preparation raw material of the high polymer nanoparticle comprises a zoledronic acid modified polycaprolactone-polypeptide copolymer, and a chemical structural formula of the copolymer is shown as follows: The high polymer nanoparticle prepared by using the zoledronic acid modified polycaprolactone-polypeptide copolymer as the raw material has the bone targeting, excellent antioxidant property and the ability of neutralizing acidic environment. The high polymer nanoparticle can exert the significant therapeutic effect (antioxidant, neutralizing acidic environment) of osteoporosis only by relying on the inherent activity of the material itself, so that a series of toxicity problems possibly caused by traditional drugs are fundamentally and greatly reduced, and a new scheme is provided for the treatment of osteoporosis.

The application discloses a preparation method of CCR2+ gamma delta T cells with anti-tumor activity and migration ability, and belongs to the technical field of cells; the method comprises the following steps: step (1), PBMC of peripheral blood of a healthy person is extracted, inoculated into complete culture medium, and added with zoledronic acid, IL-15 and metformin, and then is cultured in a T25 culture bottle; step (2), complete culture medium is supplemented, the cell concentration is adjusted, and then the cells are transferred into a T75 culture bottle for culture; step (3), complete culture medium is supplemented, the cell concentration is adjusted, glucocorticoid and nicotinamide are added, and then the cells are transferred into a T150 culture bottle for culture; step (4), cells are collected at D6, rinsed with normal saline, resuspended with complete culture medium, the cell concentration is adjusted, and then the cells are inoculated into a T300 culture bottle for culture; and step (5), complete culture medium is supplemented every two days from D8 to D16, the cell concentration is maintained, and then the cells are harvested at D16 to obtain CCR2+ gamma delta T cells.

The invention provides a culture method of human umbilical cord mesenchymal stem cells, and belongs to the technical field of cell culture. The method comprises the following steps: firstly, constructing an activation culture medium aiming at an initial culture stage and an amplification culture medium aiming at an amplification culture stage; wherein the activation culture medium takes alpha-MEM containing 10% of fetal calf serum as a basic culture medium, and alpha-tocopherol, nicotinic acid and gypenoside are added as additives, so that the cell amplification efficiency in the initial stage can be fully improved; a serum-free scheme is adopted for an amplification culture medium, RPMI-1640 is taken as a basic culture medium, and glutamine, rhG-CSF, bFGF, VEGF, transferrin, vitamin C, 2-mercaptoethanol, zoledronic acid, lenalidomide, ethanolamine and sodium selenite with specific amounts are added, so that the cell amplification speed in an amplification culture stage is remarkably increased. On the basis, a three-stage amplification process is adopted, and large-scale culture of the umbilical cord mesenchymal stem cells is realized. The method is short in culture time and high in cell quantity accumulation speed, and the culture efficiency is remarkably improved.

The invention provides an extraction method of high-performance gamma delta T immune cells and application of the high-performance gamma delta T immune cells in tumors. The method comprises the following steps: firstly, separating mononuclear cells from peripheral blood, carrying out activation induction by using a serum-free culture medium containing zoledronic acid, IL-15 and OKT3, and supplementing a culture medium containing IL-2 according to a specific proportion for multiplication culture from the third day of culture. Through the optimization process, the expression rate of TCR-gamma delta < + > is as high as 96.84%, and gamma delta T cells with high activity are obtained. An in-vivo tumor inhibition experiment shows that the cell has a remarkable growth inhibition effect on liver cancer nude mouse transplanted tumor, the effect is equivalent to that of a positive control drug, and obvious toxic and side effects are not observed. The method is stable in process and clear in component, and a reliable technical basis is provided for clinical transformation of gamma delta T cells in immunotherapy of solid tumors and hematologic tumors.

The application provides a kind of gamma delta T cell culture method and culture medium, belong to T cell culture technical field.In 1640 culture solution is added modified nanoparticle, zoledronic acid, vitamin C, glutamine, wherein, the concentration of the modified nanoparticle is 0.5-1g / L, the concentration of the zoledronic acid is 0.5-1.5 μmol / L, the concentration of the vitamin C is 200-500 μmol / L, the concentration of the glutamine is 0.1-0.2 mmol / L.The culture medium prepared by the application can efficiently stimulate gamma delta T cell expansion and improve its killing activity, and the survival rate of gamma delta T cells is also improved, and the culture method of gamma delta T cells is simple, the cost is low, and has broad application prospect.

The invention relates to an antibacterial drug, in particular to a pharmaceutical composition for treating drug-resistant bacterial infection and application of the pharmaceutical composition, including application of bacterial carbamyl phosphonic acid synthase as an antibacterial drug target in preparation of the pharmaceutical composition for treating and resisting drug-resistant bacterial infection. The antibacterial pharmaceutical composition comprises polymyxin antibiotics, zoledronic acid or pharmaceutically acceptable salts thereof, and a hydrous compound. According to the invention, a key enzyme CarB participating in an arginine biosynthetic pathway or a pyrimidine metabolic pathway in polymyxin drug-resistant bacteria is used as a target, and zoledronic acid as an inhibitor of CarB enzyme activity or a pharmaceutically acceptable salt and a hydrous compound thereof are used as synergists of polymyxin; the pharmaceutical composition of polymyxin and zoledronic acid can effectively inhibit the growth of gram-negative bacteria in vivo and in vitro. The zoledronic acid can obviously reduce the effective use dosage of the polymyxin antibiotics and reduce the toxic and side effects of the polymyxin antibiotics in clinical use. The invention can provide a new strategy for clinical treatment and application of anti-polymyxin drug-resistant bacterial infection.

A composition for treating cancer is disclosed. The composition includes a lentiviral particle and an aminobisphosphonate drug. The lentiviral particle is capable of infecting a target cell, such as a cancer cell, and includes an envelope protein optimized for targeting such target cell and a viral vector. The viral vector includes a small RNA optimized to target an FDPS mRNA sequence. The aminobisphosphonate drug includes zoledronic acid.

This invention discloses a nano-aluminum formulation of doxorubicin / zoledronic acid, its preparation method, and its application. The preparation method includes the following steps: S1: Adding an aqueous solution of zoledronic acid with a pH of 4-6 to the aqueous solution of nano-aluminum, stirring to obtain zoledronic acid-nano-aluminum; S2: Adding an aqueous solution of doxorubicin to the aqueous solution of zoledronic acid-nano-aluminum, stirring to obtain the doxorubicin / zoledronic acid nano-aluminum formulation. The DOX / ZA-Al-nano formulation of this invention can effectively inhibit tumor cell growth by promoting greater entry of doxorubicin into cells and rapid entry into the cell nucleus, and can be used for the combination therapy of osteosarcoma. Furthermore, the preparation method of this invention is simple, the reaction conditions are mild, and it is easy to operate, optimizing the preparation process and application scheme of nano-aluminum, and has the prospect of industrialization.

The invention belongs to the technical field of medicine synthesis, and discloses a preparation method of zoledronic acid dimer impurities. The preparation method is novel, simple to operate, high in product purity and suitable for industrial production; the zoledronic acid dimer impurity synthesized by the invention can be used as a standard substance for detecting zoledronic acid raw material medicines and preparations, so that the accuracy of impurity content detection and analysis is improved, the impurity in the zoledronic acid raw material medicines and preparations is favorably controlled, and the quality of zoledronic acid finished products is further improved.

The application belongs to the technical field of biotechnology, and particularly relates to a staged precise regulation in vitro expansion culture method of high-activity gamma delta T cells. In the synergistic activation stage, the complex activator containing zoledronic acid, IL-2, IL-15, IL-12 and IL-21 is used to significantly improve the early activation level of the gamma delta T cells; in the dynamic expansion stage, the concentration of metformin is adjusted step by step to support the continuous and efficient proliferation of the cells; in the gradient maturation stage, the combination system of N-acetyl cysteine, TWS119 and DL-alpha tocopheryl acetate is introduced to help maintain the functional activity and antioxidant state of the cells in the later culture stage. The gamma delta T cells with a purity higher than 90% and an expansion multiple more than 100 times can be obtained by using the method to culture for 10 days, and the cells exhibit significant killing activity to tumor cells, are suitable for the adoptive immunotherapy of tumor and infectious diseases, and have good clinical application prospects.

The invention discloses a zoledronic acid hollow nanosphere, a zoledronic acid hollow nanosphere loaded paclitaxel antitumor material and a preparation method and application thereof, the preparation method of the zoledronic acid hollow nanosphere comprises the following steps: dispersing a zeolite imidazole framework 8 in methanol, adding an aqueous solution of zoledronic acid, standing for 60-180 min, centrifuging and cleaning to obtain the zoledronic acid hollow nanosphere loaded paclitaxel antitumor material. The zoledronic acid hollow nanospheres are obtained; the zoledronic acid hollow nanosphere loaded paclitaxel antitumor material can be prepared by loading paclitaxel on the zoledronic acid hollow nanosphere. According to the anti-tumor material, the synergistic anti-tumor effect of the zoledronic acid hollow nanospheres and the paclitaxel can be effectively exerted, and breast cancer cells MCF-7 can be remarkably killed.

A composition for treating cancer is disclosed. The composition includes a lentiviral particle and an aminobisphosphonate drug. The lentiviral particle is capable of infecting a target cell, such as a cancer cell, and includes an envelope protein optimized for targeting such target cell and a viral vector. The viral vector includes a small RNA optimized to target an FDPS mRNA sequence. The aminobisphosphonate drug includes zoledronic acid.

The invention discloses an application of a bisphosphonate compound in preparation of an antigen-specific activated T cell preparation. The bisphosphonate compound is etidronate sodium as shown in a formula I; the clodronate sodium is shown as a formula II; the pamidronate sodium is shown as a formula III; the alendronate sodium trihydrate is as shown in a formula IV; zoledronic acid is as shown in formula V; the ibandronic acid is as shown in a formula VI; the risedronate sodium is shown as a formula VII; minodronic acid is shown as a formula VIII. The bisphosphonate compound can specifically activate T cells and remove target cells, and the target cells comprise various tumor cells, aging cells and infected cells.

The application belongs to the technical field of biomedical materials, and provides a composite gel loaded with strontium ions / zoledronic acid and a preparation method thereof, which comprises the following steps: preparing thiol-modified sodium hyaluronate and double bond-modified carboxymethyl chitosan; preparing strontium ion-doped mesoporous silica microspheres, thiol-modified strontium ion-doped mesoporous silica microspheres and thiol-modified strontium ion-doped mesoporous silica microspheres loaded with zoledronic acid in sequence; dissolving the thiol-modified sodium hyaluronate and the double bond-modified carboxymethyl chitosan in deionized water respectively, and then stirring and mixing the thiol-modified sodium hyaluronate, the double bond-modified carboxymethyl chitosan and the thiol-modified strontium ion-doped mesoporous silica microspheres loaded with zoledronic acid, and adding a photoinitiator and irradiating under ultraviolet light. The composite gel prepared by the application integrates mechanical support, biocompatibility, intelligent drug release and synergistic osteogenesis / angiogenesis, and can be applied to the preparation of high-performance osteoporotic bone defect repair materials.

The present invention relates to the use of arginine, and a pharmaceutical composition containing arginine. First, provided in the present invention is an inflammation model successfully constructed by using zoledronic acid. The model can be used for screening a drug for inflammation-related diseases, thereby facilitating for research on inflammation-related mechanisms and pharmaceutical development. The construction method has good repeatability and stability. Further provided in the present invention is the use of arginine and a pharmaceutical composition thereof. Studies show that both arginine and the composition of arginine and zoledronic acid can effectively treat, prevent and / or relieve side reactions such as renal injury, and inflammation that occurs during the treatment by using zoledronic acid.

Formulation of nanoparticles of calcium phosphate, preferably hydroxyapatite, said nanoparticles being modified with lecithin, preferably phosphatidylcholine, said formulation having an enhanced cellular uptake and being a carrier for bisphosphonate, characterised in that bisphosphonate is selected from the group of bisphosphonate drugs approved for medical use, the group comprising alendronate and zoledronate, bisphosphonate is encapsulated in calcium phosphate nanoparticles in an amount up to 40% by mass, and the nanoparticles are less than 200 mn in size. Method of obtaining said formulation, comprising the steps: a. dissolving Ca(N03)2. 4H2O in a lecithin solution, b. dissolving (NH4)2HP04 in a bisphosphonate solution, c. adjusting the pH of the solution resulting from step a. and of the solution resulting from step b. to the value of 10, d. mixing the solutions from step c. in a reactor to obtain a suspension, e. centrifuging the suspension from step d. to obtain precipitate, f. purifying the precipitate from step e. by rinsing it four times with ultrapure water and centrifuging, g. drying the precipitate from step f. at 50° C. for 12-24 h, h. grinding the precipitate from step g. in a ball mill for 10 minutes at a speed of 150 rpm, wherein step d. is carried out in a continuous or batch reactor.

The invention is applicable to the technical field of biomedical materials, and provides strontium ion / zoledronic acid loaded composite gel and a preparation method thereof, and the preparation method comprises the following steps: preparing sulfydryl modified sodium hyaluronate and double bond modified carboxymethyl chitosan; the preparation method comprises the following steps: sequentially preparing mesoporous silica microspheres doped with strontium ions, sulfhydrylated mesoporous silica microspheres doped with strontium ions, and sulfhydrylated mesoporous silica microspheres loaded with zoledronic acid doped with strontium ions; the preparation method comprises the following steps: respectively dissolving sulfydryl-modified sodium hyaluronate and double-bond-modified carboxymethyl chitosan in deionized water, stirring and mixing with zoledronic acid-loaded sulfhydrylated strontium ion-doped mesoporous silica microspheres, adding a photoinitiator, and irradiating under ultraviolet light. The composite gel prepared by the invention integrates mechanical support, biocompatibility, intelligent drug release and synergistic osteogenesis / vascularization promotion, and can be applied to preparation of high-performance osteoporotic bone defect repair materials.

The invention discloses a pharmaceutical composition, which contains carboxamide triazole and bisphosphate which have the same or different specifications and are administered simultaneously or respectively, and the bisphosphate is at least one of clodronate sodium, alendronate sodium, risedronate sodium and zoledronic acid. Researches show that the anti-tumor and anti-inflammatory effects of the carboxamidotriazole combined with the diphosphate are better than those of single drugs DES and ZOA; meanwhile, compared with the single administration of the zoledronic acid with the concentration of 0.1 mg / kg or the single administration of the CAI with the concentration of 40 mg / kg and 80 mg / kg, the combined administration of the zoledronic acid with the concentration of 0.1 mg / kg and the combined administration of the CAI with the concentration of 40 mg / kg and 80 mg / kg can significantly inhibit the growth and proliferation of human lung cancer A549-luc xenotransplantation tumors in bone metastasis of B-NDG mice, and has an unexpected combined synergistic effect. And the zoledronic acid and CAI combined administration group can significantly prolong the survival time of the human lung cancer A549-luc cells in a non-small cell lung cancer bone metastasis model animal established in a B-NDG mouse. The traditional Chinese medicine composition has the effects of remarkable combined synergism and less toxic and side effects.

The invention relates to bionic chitosan hybrid nanogel for treating prostatic cancer osseous metastasis and a preparation method and application thereof, the hybrid nanogel is prepared by the following steps: carrying out a cross-linking reaction on a chitosan monomer and a cross-linking agent glutaraldehyde, introducing ultra-small ferroferric oxide nanoparticles in the reaction process to form the hybrid nanogel, and then loading zoledronic acid to obtain the bionic chitosan hybrid nanogel for treating prostatic cancer osseous metastasis. And further coating a prostate cancer cell membrane. After entering a tumor-bearing nude mouse body through tail vein injection, the pH response type bionic hybrid nanogel prepared by the invention has the advantages of remarkable prostate cancer bone metastasis inhibition and excellent T1 magnetic resonance imaging performance, and has potential clinical application value.

The invention provides a novel application of zoledronic acid in ALS treatment, belongs to the field of biological medicine, and particularly relates to a novel application of zoledronic acid in treatment of amyotrophic lateral sclerosis, animal experiments and patient-derived cell experiments prove the treatment effect of zoledronic acid on ALS, and the application of zoledronic acid in ALS treatment is a novel application of zoledronic acid in ALS treatment. And a new treatment scheme and a new research direction are provided for treatment of amyotrophic lateral sclerosis.

The invention belongs to the field of biomedical materials, and particularly discloses targeted multi-controlled-release functionalized nanoparticles as well as a preparation method and application thereof. The functionalized nanoparticles are prepared according to the following steps: S1, dissolving PLGA or PLGA and functional compound molecules in acetone, dropwise adding into a TPGS aqueous solution, and volatilizing and centrifuging to obtain drug-loadable PLGA nanoparticles; s2, after the nano-particles react with tannic acid, centrifugal purification is conducted, the nano-particles are resuspended in a TPGS solution for self-assembly, then zoledronic acid is added for a reaction, and the nano-particles are obtained. According to the nanoparticles, bone targeted enrichment is realized by virtue of the affinity of zoledronic acid and bone hydroxyapatite, multiple drug controlled release is realized by virtue of tannic acid crosslinking, therapeutic factors can be stably released for a long time, an osteoporosis pathological microenvironment is corrected, side effects are reduced, and the nanoparticles can be used for treating osteoporosis. The preparation process is simple and efficient, the cost is low, and the reproducibility is good.

The invention discloses a culture solution of Vdelta2T cells as well as a culture method and application of the culture solution. The culture solution comprises an activation culture medium and an amplification culture medium, and a serum-free culture medium is taken as a basic solution; calcium chloride, IL-2, IL-15, IL-21, zoledronic acid, L-glutamine, beta-mercaptoethanol, N-acetylcysteine, human AB serum and silibinin are added into the serum-free culture medium of the activated culture medium; iL-2, human AB serum and hyperoside are added and contained in a serum-free culture medium of the amplification culture medium. According to the culture solution of the Vdelta2T cells and the multiplication culture method for culturing the Vdelta2T cells by using the culture solution, the in-vitro amplification capacity (the amplification multiple is as high as 7416 times) of the Vdelta2T cells can be remarkably improved, the purity of amplified NK cells is as high as 99%, and the tumor cell killing power (the tumor killing effect is relatively good when the ratio of E to T is 1: 1) can be remarkably improved.

This invention provides a nanoformulation capable of enhancing the immune response to in situ tumor vaccines. The nanoformulation comprises zoledronic acid, all-trans retinoic acid, and metal ions. Preferably, the metal ion is a lanthanide metal, such as Gd. 3+ Preferred, zoledronic acid: Gd 3+ The mass ratio of all-trans retinoic acid is 4:1:5. The nano-formulation consists of zoledronic acid and Gd... 3+ Zol / Gd-NPs nanocoagulation polymers were formed by mixing in water. All-trans retinoic acid was dissolved in anhydrous ethanol to prepare albumin-encapsulated nanoparticles (A-NPs), which were then mixed with the Zol / Gd-NPs nanocoagulation polymers and sonicated to obtain the final product. These nanoparticles, on the one hand, can utilize zoledronic acid to eliminate macrophages, thereby reversing the inhibition of intratumoral dendritic cells (DCs) by the tumor immunosuppressive microenvironment; on the other hand, all-trans retinoic acid can significantly increase the expression of MHC-I and tumor antigens in tumor cells, thus ensuring the activation of CD8. + T cells can effectively recognize and kill tumors, generating a systemic anti-tumor immune response.