14results about How to "Reduce systemic toxicity" patented technology

The invention discloses an application of targeted improvement of a high-potassium microenvironment in osteosarcoma immunotherapy, vanadium disulfide nano-particles are synthesized by taking vanadyl acetylacetonate as a raw material and adopting a high-temperature oil phase method, the particles can be accelerated to decompose at 42 DEG C or above so as to release hydrogen sulfide and vanadate, the vanadate can be specifically combined with E2 conformation of Na < + >-K < + >-ATP enzyme, and thus the stability of the particles is improved. According to the present invention, the HSP protein is released, the conversion of the HSP protein to E1 conformation is blocked, the continuous inward flow of K < + > is inhibited, such that the potassium ion concentration in the T cell is reduced, the function inhibition on the T cell is relieved, and the released hydrogen sulfide can further enhance the thermal effect by inhibiting the HSP protein so as to form the ion regulation-immune activation dual mechanism to improve the T cell killing ability. According to the scheme, the high potassium ion level of the osteosarcoma microenvironment is regulated and controlled through vanadate, hydrogen sulfide can enhance immune response and improve the anti-tumor function of T cells by enhancing the heat effect and the synergistic effect of vanadate, and an efficient and low-toxicity new strategy is provided for osteosarcoma treatment.

The invention discloses a brain-targeted nasal-spray amphotericin B phospholipid complex and a preparation method and application thereof, and belongs to the technical field of pharmaceutical preparations, the brain-targeted nasal-spray amphotericin B phospholipid complex is prepared by adopting a film dispersion method, and the preparation method comprises the following steps: dissolving 15-hydroxystearic acid polyethylene glycol ester, phospholipid, cholesterol, amphotericin B and optional other auxiliary components in a solvent, removing the solvent until a film is formed, and drying to obtain the brain-targeted nasal-spray amphotericin B phospholipid complex. And carrying out hydration dispersion to obtain the amphotericin B-loaded phospholipid complex. According to the amphotericin B sodium deoxycholate injection, the problems that the traditional amphotericin B sodium deoxycholate injection is high in renal toxicity, the intrathecal injection is poor in solubility, and low in bioavailability and patient compliance, large in side effect and the like due to the fact that the traditional amphotericin B sodium deoxycholate injection is difficult to penetrate through a blood brain After nasal administration, the drug is quickly delivered into the brain, so that the slow release of the drug is realized, the intracerebral bioavailability of the drug is improved, high brain targeting and low systemic toxic and side effects are realized, and good clinical application value and market prospect are achieved.

The invention provides a personalized cancer vaccine based on apoptosis vesicles and a preparation method and application thereof, and belongs to the technical field of biological medicine, the personalized cancer vaccine comprises apoptosis vesicles, an immunologic stimulant and a biocompatibility carrier; the apoptosis vesicles are extracellular vesicles generated after tumor cells are subjected to apoptosis induction; the biocompatible carrier is a modified chitosan hydrogel, and the biocompatible carrier is a modified chitosan hydrogel; the immunologic stimulant is loaded in the apoptosis vesicle, and the apoptosis vesicle loaded with the immunologic stimulant is embedded into the modified chitosan hydrogel. According to the invention, apoptosis vesicles generated by induction of tumor cells of a patient are taken as a core, the apoptosis vesicles have a natural tumor antigen library and a strong immune activation capability, and personalized precise treatment can be realized; meanwhile, the invention provides a preparation method and application in postoperative tumor recurrence prevention and treatment, and provides technical support for clinical transformation.

The invention discloses Fe (at) MoS2 hydrogel for sensitizing immunotherapy and a preparation method of the Fe (at) MoS2 hydrogel. The hydrogel comprises ferrous sulfate, molybdenum disulfide and a hyaluronic acid hydrogel matrix. The hydrogel can continuously release iron ions in a tumor slightly acidic environment, Fe is reduced into Fe by utilizing the catalytic action of MoS, and circular supply of Fe is realized, so that tumor cells are efficiently and enduringly induced to generate ferroptosis. More importantly, it is found that the Fe-coated MoShydrogel can specifically up-regulate expression of IL-36 gamma and CXCL2 in a tumor microenvironment for the first time, and by activating an IL36 gamma / CXCL2 / CXCR2 signal axis, mononuclear macrophages are recruited and remodeled, and the immunosuppression microenvironment is reversed. In-vivo experiments show that when the hydrogel is combined with an immune checkpoint inhibitor (such as an alphaPD-1 antibody), a remarkable synergistic anti-tumor effect can be generated, and the complete remission rate is greatly improved.

The invention relates to HIF-1alpha siRNA lipid nanoparticles and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The preparation method comprises the following steps: S1, dissolving ionizable lipid, neutral lipid, cholesterol and pegylated lipid in an organic solvent to obtain an oil phase; the method comprises the following steps: dissolving HIF-1alpha siRNA in a first buffer solution to obtain a water phase; s2, mixing the oil phase and the water phase by adopting a micro-fluidic technology, diluting with a second buffer solution, removing the organic solvent, and concentrating to obtain the HIF-1alpha siRNA lipid nanoparticles, the targeted delivery of the HIF-1alpha siRNA is realized, so that the HIF-1alpha siRNA is effectively delivered to the rheumatoid arthritis diseased region through the delivery system to play a therapeutic role.

The invention provides a nano preparation for preparing a medicine for inhibiting prostatic cancer and a preparation method of the nano preparation, and relates to the technical field of nano medicinal preparations. The nano preparation comprises the following components in parts by mass: traditional Chinese medicine components and a nano carrier, the traditional Chinese medicine component comprises 15-45 parts of a Chinese yam extract, 5-15 parts of a madder extract, 8-20 parts of cuttlebone superfine powder, 10-25 parts of dragon bone superfine powder and 10-25 parts of oyster superfine powder; the nano-carrier comprises 5-20 parts of phospholipid, 2-10 parts of cholesterol, 1-5 parts of fatty acid, 3-15 parts of polyethylene glycol and 1-5 parts of a surfactant. The average particle size of the nano preparation is 80-150 nm, the polydispersity index PDI is smaller than or equal to 0.30, and the encapsulation efficiency is larger than or equal to 75%. According to the invention, active ingredients of traditional Chinese medicines are combined with a nanotechnology, so that the bioavailability and the tumor targeting property are remarkably improved, the pH-responsive release characteristic is achieved, a remarkable inhibition effect on various prostate cancer cell lines is shown, tumor growth can be effectively inhibited, metastasis can be reduced, and a good application prospect is achieved.

The invention discloses an application of a benzo-aza derivative in preparation of a medicine for preventing or treating atherosclerosis, the benzo-aza derivative is a compound with a chemical structure as shown in a formula I, or a pharmaceutically acceptable salt, a precursor or a metabolite of the compound, and in the formula I, X is halogen or H. The traditional Chinese medicine composition has the technical effects that the plaque stabilizing effect is obvious, the plaque composition is improved, the necrosis core area in the plaque is reduced, the total plaque load can be effectively reduced, the lesion progress is delayed / reversed, the dependence on lipid reduction is avoided, the treatment blank is filled, a brand new plaque stabilizing treatment strategy is provided, and the clinical problem of residual cardiovascular risks is expected to be solved. The safety is good, the organ specificity is high, and the whole body toxicity is low. The invention provides a new treatment normal form, new use of old medicines and large clinical transformation potential, and can be used as a supplement and enhancement of a basic therapy (such as statin lipid reduction) to form a combined treatment scheme of lipid reduction and spot stabilization, thereby realizing multi-channel cooperative control of atherosclerosis.

This invention relates to the fields of biomedical engineering and drug delivery technology, specifically disclosing a novel targeted drug delivery system based on rosehip extracellular vesicles, comprising: preparing rosehip-derived extracellular vesicles; preparing drug-loaded vesicles; and preparing targeted modified drug-loaded vesicles. This invention utilizes the specific downregulation of stem cell-related pathways by rosehip components, while simultaneously leveraging doxorubicin to kill conventional tumor cells, forming a complementary therapeutic mechanism to fundamentally reduce the risk of tumor recurrence. The phenylboronic acid group of DSPE-PEG-PBA specifically recognizes sialic acid overexpressed on the surface of tumor cells, significantly increasing drug accumulation in tumor tissues while reducing distribution in normal tissues. By leveraging the natural biocompatibility and low immunogenicity of RHNVs, combined with the long-circulating properties of the PEG chain, systemic toxicity is minimized while ensuring delivery efficiency, particularly reducing the cardiotoxicity and bone marrow suppression of doxorubicin.

This invention discloses a nystatin microsphere with targeted enhanced antifungal function, its preparation method, and its application. The microsphere uses sodium alginate as a carrier, internally encapsulating the antifungal drug nystatin. The surface is covalently modified with the β-glucan binding domain of the Dectin-1 protein, constructing a smart drug delivery system with fungal targeting function. The microsphere preparation process is simple and reproducible, and can be scalable using an emulsion-ionic crosslinking method combined with protein coupling technology. In vitro characterization shows that the microspheres have uniform particle size and stable dispersion, and Dectin-1 modification significantly enhances their specific binding ability against Candida albicans. This targeted delivery system, while successfully preserving drug activity, significantly improves the antifungal efficiency of nystatin through Dectin-1-mediated targeting, achieving efficacy close to that of free drug, and providing a new strategy for constructing highly efficient and long-acting antifungal agents.

Compounds based on sealin-4 binding peptide (C4BP) have been specifically designed for radiopharmaceuticals. Specifically, C4BP-integrated compounds and compositions have been designed for use specifically in the detection and treatment of pancreatic cancer. Embodiments are compounds comprising a peptide, a spacer (or spacer-free), and a chelating agent, wherein the compound binds to CLDN4. The compounds can bind to metal radioisotopes to produce radiopharmaceuticals. The range of applications of these compounds includes diagnostic procedures, therapeutic interventions, and targeted delivery of radionuclides to tissues expressing CLDN4. Described herein are detailed methods of radiopharmaceuticals in combination with CPB for diagnosis, treatment, and targeted delivery in tissues expressing CLDN4.

The application relates to a MYH2-FIGN interaction blocking amino acid compound and an application thereof, and relates to the fields of polypeptide drugs and tumor prevention and treatment. The MYH2-FIGN interaction blocking amino acid compound is an amino acid sequence as shown in SEQ ID NO:1 or SEQ ID NO:3 or a polypeptide derivative thereof. The application further discloses a pharmaceutical composition containing the MYH2-FIGN interaction blocking amino acid compound and a pharmaceutically acceptable carrier. The application first designs a polypeptide drug targeting the MYH2-FIGN interaction interface, and compared with traditional small molecules, the polypeptide drug has specificity for MYH2-FIGN interaction inhibition, and through fusion of an iRGD peptide, not only is the polypeptide cell penetration problem solved, but also the polypeptide drug is endowed with tumor targeting, the bioavailability of the drug is improved, and the systemic toxicity is reduced. The polypeptide drug can adopt various drug dosage forms, and the preparation process is simple.

This invention discloses a ZIF-8 nanomedicine delivery system co-loaded with doxorubicin and siTDRKH, its preparation method, and its applications, belonging to the fields of biomedicine and nanomaterials technology. The nanomedicine delivery system uses the zeolite imidazole ester framework material ZIF-8 as a carrier. Its porous structure encapsulates the chemotherapeutic drug doxorubicin within the framework, and small interfering RNA targeting the TDRKH gene is loaded onto the surface through electrostatic adsorption. This structure exhibits high pH responsiveness: it remains stable under normal physiological conditions (pH 7.4), preventing premature drug leakage; upon entering the slightly acidic environment of a tumor (pH 6.5) or a lysosomal environment (pH 5.0), the ZIF-8 framework immediately disintegrates, achieving targeted and synergistic release of the loaded drug.

This invention is a divisional application of application number 202010500967.1. The invention relates to a layered double hydroxide material system, its preparation method, and its application, specifically the application of LDH / EDTA layered double hydroxide materials in the preparation of antitumor drugs. The LDH / EDTA layered double hydroxide material is a zinc-aluminum layered double hydroxide loaded with ethylenediaminetetraacetic acid (EDTA); in the EDTA-loaded zinc-aluminum layered double hydroxide, EDTA is anion-exchange-intercalated into the interlayer space of the zinc-aluminum layered double hydroxide; the surface of the EDTA-loaded zinc-aluminum layered double hydroxide is positively charged.

The invention discloses a trabectedin-loaded nano-micelle and oxaliplatin-loaded drug combination composition and application, and relates to the technical field of delivery and drug combination, and the trabectedin-loaded nano-micelle and oxaliplatin-loaded drug combination composition comprises trabectedin-loaded nano-micelle and oxaliplatin. The invention also discloses an application of the combined pharmaceutical composition in preparation of antitumor drugs. According to the invention, a pH-sensitive amphiphilic biodegradable material (such as PCL-PEOz) and a chemical drug are self-assembled to form stable micelles, so that the bioavailability of the drug is improved, the critical concentration of the micelles is reduced, and long-acting circulation in vivo is realized; the system can be combined with oxaliplatin for use, so that the sensitivity of tumor cells to oxaliplatin is promoted, the synergistic effect of chemotherapy and immunotherapy is exerted, the treatment effect of malignant tumors is improved, and the tumor microenvironment is improved.