108 results about "Systemic administration" patented technology

The invention discloses a microneedle-tranexamic acid nanofiber membrane and a preparation method thereof, and belongs to the technical field of biomedical materials. The preparation method comprises the following steps: preparing a soluble microneedle (DMN) by utilizing a hydrophilic polymer polyvinylpyrrolidone (PVP), fixing the microneedle on an electrostatic spinning receiver, and carrying out electrostatic spinning by using an electrostatic spinning solution containing tranexamic acid TA to prepare a microneedle-tranexamic acid nanofiber membrane, namely TA-PVP-DMN. The prepared microneedle-tranexamic acid nanofiber membrane is simple in process and high in epidermal permeability, meanwhile, the safety problem caused by systemic administration of tranexamic acid can be avoided, and finally the purposes of safely and effectively improving facial pigmentation and treating chloasma can be achieved.

Provided are methods for treating cancer using local administration of certain CpG oligonucleotides (CpG ODN) and systemic administration of a checkpoint inhibitor such as an anti-PD-1 antibody, an anti-PD-L1 antibody, and / or an anti-CTLA-4 antibody. In preferred embodiments, the CpG ODN are selected based on their propensity to induce high amounts of interferon alpha (IFN-α) and T-cell activation relative to interleukin-10 (IL-10) and B-cell activation. In certain embodiments, the methods further include pretreatment with radiotherapy, to potentiate the combination immunotherapy.

Provided herein are methods and compositions for treating a subject suffering from an enzyme deficiency in the central nervous system (CNS). The bifunctional fusion antibody provided herein comprise an antibody to an endogenous blood brain barrier (BBB) receptor and an enzyme deficient in GM1 gangliosidosis or GM1. The fusion antibodies provided herein comprise galactosidase beta-1 (GLB1). The methods of treating an enzyme deficiency in the CNS comprise systemic administration of a fusion antibody provided herein.

The present disclosure relates to an approach, referred to as Regionally Activated Interstitial Drugs (RAID), that does not require viral vectors, but allows for tunable, noninvasive, long-term neuromodulation with small molecules. RAID utilizes noninvasive delivery of an engineered protein enzyme into the brain, which then binds to the brain parenchyma and can locally convert a blood-brain-barrier (BBB)-permeable inert prodrug into an active neuromodulatory drug. As long as the RAID enzyme is present in the parenchyma, localized neuromodulation can be achieved with systemic administration of the BBB-permeable prodrug even in the absence of the opened BBB. Alternatively, gene delivery encoding the RAID enzyme offers prolonged expression and precise spatial control, enabling long-term and adaptable neuromodulation.

Lentiviral vector (LV) formulations, and pharmaceutical compositions comprising such LV formulations, with improved stability and suitable for systemic administration are provided. Methods for treating disorders, especially blood disorders, using systemic administration of LV formulations are also provided.

Pharmaceutical compositions and therapeutic methods are provided comprising a single-domain antibody consisting of SEQ ID NO:1 and a pharmaceutically acceptable carrier. The antibody inhibits KRAS GTPase activity and inhibits phosphorylation of STAT3. In certain embodiments, inhibition of KRAS results in decreased phosphorylation of ERK1 / 2. The antibody reduces tumor cell surface PD-L1 expression and reduces VEGF production. The antibody crosses the blood-brain barrier following systemic administration and may exhibit sustained biological activity in vivo. Methods are provided for treating KRAS-mutant cancers, including pancreatic cancer and triple negative breast cancer, and for enhancing anti-tumor immunity through reduction of PD-L1 expression.

The invention discloses application of ceftriaxone sodium in preparation of a medicine for preventing and / or treating pulmonary nodules, and belongs to the technical field of tumor prevention and treatment, ceftriaxone sodium is converted into inhalable aerosol particles through an aerosol inhalation device, targeted delivery of the medicine to the lung can be achieved, systemic adverse reactions caused by systemic administration are remarkably reduced, and the curative effect of the medicine is improved. Therefore, the medicine has a treatment effect on pulmonary nodules. Experimental results in the early stage prove that ceftriaxone sodium with different concentrations is subjected to aerosol inhalation to intervene in a mouse pulmonary nodule model induced by uratan, and the ceftriaxone sodium has a good prevention and treatment effect. The research can provide new experimental basis and reference for development of lung nodule related prevention and treatment medicines, provides new technical ideas for prevention and treatment of other diseases, and has important academic value and potential of further development and research.

Lentiviral vector (LV) formulations, and pharmaceutical compositions comprising such LV formulations, with improved stability and suitable for systemic administration are provided. Methods for treating disorders, especially blood disorders, using systemic administration of LV formulations are also provided.

The object of the present invention is to provide an active ingredient for a systemically administered mRNA pharmaceutical that expresses an antibody specific to the V antigen protein or its homologous protein of Gram-negative bacteria, and a systemically administered mRNA pharmaceutical using the same. [Solution] mRNA containing an antibody coding region encoding a specific scFv antibody against the V antigen protein or its homologous protein of pathogenic Gram-negative bacteria is useful as an active ingredient in mRNA pharmaceuticals for systemic administration.

The invention discloses a cationic peptide compound for targeting cartilage as well as a preparation method and application of the cationic peptide compound. The cationic peptide compound has a structural general formula as shown in the specification: R-(Xa-Nlys-Yb) n, wherein R is H, a drug active molecule or a group containing a signal marker, and X and Y are independently selected from any one of glycine residues and imidic acid residues; nlys is a residue of N-(4-aminobutyl) glycine; a and b are independently selected from any integer between 0 and 3; n is any positive integer from 3 to 10. The compound can target a glycosaminoglycan chain in cartilage through electrostatic interaction, has an effect of resisting protease degradation, and is beneficial to prolonging the in-vivo circulation time. The compound supports systemic administration, can be used for marking whole body cartilage through intravenous injection, is used for monitoring cartilage development, aging and pathological changes in real time, and has wide application potential in the aspects of molecular imaging, drug delivery and biological materials for treating cartilage-related diseases.

Provided herein are methods and compositions for treating a subject suffering from a deficiency in iduronate 2-sulfatase in the CNS. The methods include systemic administration of a bifunctional fusion antibody comprising an antibody that crosses the blood brain barrier (BBB) and an iduronate 2-sulfatase.

This invention discloses a nanodecoy receptor that blocks the IL-17 signaling pathway, including IL-17RA-CMVs carrying a fusion sequence of PDGFR-TMD and IL-17RA. This invention also provides a method for preparing the aforementioned nanodecoy receptor that blocks the IL-17 signaling pathway, comprising the following steps: S1. Using genetic engineering, IL-17RA and PDGFR-TMD are fused and designed, and a lentivirus carrying the IL-17RA and PDGFR-TMD fusion sequence is coated onto mammalian cells. A cell line stably expressing the IL-17RA and PDGFR-TMD fusion sequence is established in mammalian cells through lentivirus transfection; S2. The cell line from step S1 is taken, and cell membrane vesicles are prepared by ultrasonic disruption and permeabilization extrusion until the fusion sequence of IL-17RA carrying PDGFR-TMD is displayed at high density and correctly oriented on the outer surface of the cell membrane vesicles, forming IL-17RA-CMVs. The nano-decoy receptor of the present invention can efficiently and broadly block the interaction between IL-17 and IL-17RA, avoid such systemic side effects, and achieve treatment only through local minimally invasive delivery, thus solving the side effects problem caused by existing systemic drug administration.

The invention relates to a biodegradable slow-release film, a preparation process and an intracranial postoperative adjuvant therapy method. The film comprises a film base material and a medicine component, the film base material is a biodegradable high polymer material, and the medicine component can be slowly released along with the gradually degraded film base material. According to the treatment scheme provided by the invention, local administration is directly carried out on the wound surface in the brain, residual tumor cells and a tumor microenvironment are directly targeted after the drug is slowly released, the local concentration and the treatment effect of the drug are greatly improved, meanwhile, far-end relapse is prevented by activating systemic immune memory, and serious toxic and side effects caused by systemic administration are avoided; a multi-layer electrostatic spinning structure is utilized to realize sequential controlled release of different drugs, and the natural process of immune response is simulated; therefore, the pain of a patient and the operation risk are reduced.

Compositions for intranasal delivery of olanzapine and methods for their use to treat various symptoms of schizophrenia, schizoaffective disorder, and bipolar I disorder, such as acute agitation, mania, and mixed episodes. Intranasal olanzapine compositions comprise dodecyl maltoside to improve bioavailability of olanzapine and is administered via nasal mucosa to avoid direct systemic administration.

The invention discloses a bispecific antibody fusion protein, a recombinant oncolytic virus and application of the bispecific antibody fusion protein and the recombinant oncolytic virus in preparation of drugs for treating tumors, the recombinant oncolytic virus can express and secrete a bispecific antibody HER2-BiTE, and the bispecific antibody HER2-BiTE can serve as an adapter to recruit T cell targeted HER2 positive tumor cells, so that the killing effect of the T cells on the tumor cells is improved; meanwhile, the oncolytic virus causes tumor cell lysis, tumor-associated antigen release and tumor microenvironment remodeling; the BiTE plays a role in tumor sites, so that the adverse reaction of systemic administration is relieved. The synergistic effect of the oncolytic virus and the bispecific antibody improves the tumor treatment effect.

This invention relates to a glucose-responsive antibacterial nanocomposite microneedle patch, its preparation method, and its application, belonging to the field of biomedical materials technology. The glucose-responsive antibacterial nanocomposite microneedle patch is an integral soluble microneedle. The functional component of the microneedle material is a nanocomposite CIP / GOx@ZIF-8, which uses ZIF-8 as a nanocarrier, co-loading ciprofloxacin hydrochloride and glucose oxidase. This invention synthesizes CIP / GOx@ZIF-8 using a one-step self-assembly method, achieving co-loading of CIP HCl and GOx. Furthermore, this invention further prepares CIP / GOx@ZIF-8 into microneedles. The preparation method is simple, easy to use, and allows for self-administration. Topical application to skin wounds is safer and more effective than systemic administration, further improving drug delivery efficiency and delivering therapeutic agents deep into the wound, promoting wound healing. This invention combines multiple therapeutic mechanisms, significantly enhancing the antibacterial properties of the microneedles and achieving the treatment of bacterially infected diabetic wounds.

The invention relates to the technical field of biological medicines, in particular to a hydroxyl-alpha-sanshool gel plaster, a preparation method thereof and application of the hydroxyl-alpha-sanshool gel plaster in preparation of a medicine for treating peripheral neuropathic pain. The preparation method specifically comprises the following steps: (1) mixing hydroxyl-alpha-sanshool with hydroxypropyl-beta-cyclodextrin for reaction, and removing a solvent to obtain a reactant; (2) filtering a reactant, and freeze-drying the reactant to obtain a hydroxyl-alpha-sanshool cyclodextrin inclusion compound; and (3) preparing the hydroxyl-alpha-sanshool cyclodextrin inclusion compound into the hydroxyl-alpha-sanshool gel plaster. The invention aims to construct a hydroxypropyl-beta-cyclodextrin inclusion compound system through a molecular inclusion technology so as to improve the water solubility of HAS and increase the stability of HAS. The prepared gel plaster is used for local treatment of peripheral nerve pathological pain, and aims to avoid loss caused by a first-pass effect, improve patient discomfort caused by frequent administration and reduce side effects caused by systemic administration.

The invention relates to the technical field of medicines, and particularly discloses an engineered drug-loaded macrophage for resisting transplant rejection. PD-L1 is overexpressed on the surface of a cell membrane of the engineered drug-loaded macrophage, and the engineered drug-loaded macrophage internally contains nanoparticles encapsulated with rapamycin. Due to the biological characteristic that the macrophages can respond to inflammation signals, the engineered drug-loaded macrophages can be efficiently recruited to rejection reaction parts by chemotactic factors of transplantation parts, and the engineered drug-loaded macrophages can penetrate a tissue barrier as an active carrier, respond to external stimulation to exocytosis and release nanoparticles encapsulated with rapamycin after reaching a target position, and can be used for preparing a drug carrier. Local precise delivery of PD-L1 and rapamycin is realized, and immunosuppression toxicity of systemic administration is reduced.

Disclosed are combination therapy methods useful for the therapeutic treatment of cancer by combining local administration of compositions containing antineoplastic particles, such as taxane particles, with systemic administration of compositions containing immunotherapeutic agents. Local administration methods include topical application, pulmonary administration, intratumoral injection, intraperitoneal injection, and intracystic injection.

To provide lentiviral vector (LV) formulations with improved stability and suitable for systemic administration, and pharmaceutical compositions comprising such LV formulations, and also to provide methods for treating disorders, especially blood disorders, using systemic administration of LV formulations.SOLUTION: Provided is a recombinant lentiviral vector preparation comprising: (a) a therapeutically effective amount of a recombinant lentiviral vector; (b) a TRIS-free buffer system; (c) a salt; (d) a surfactant; and (e) a carbohydrate, wherein the pharmaceutical composition is suitable for systemic administration to a human patient.SELECTED DRAWING: None

The present disclosure relates to LNP formulations useful for uptake in the CNS or brain, for example, in some cases wherein the LNP is conjugated to an antigen binding fragment of an anti-transferrin receptor antibody. The present disclosure also relates to methods of delivering lipid nanoparticles (LNPs) systemically, for uptake in vivo in the central nervous system (CNS), such as to brain cells, and methods for assessment of the extent of uptake in CNS cells, such as brain cells. In some cases, methods allow for high throughput screening of multiple different LNPs in parallel.

The present invention relates to a composition comprising the supernatant of a supernatant of a blood mononuclear cell (PBMC) cell culture for use in the treatment / or prevention of allergies or allergic reactions caused by the administration of at least one food and / or inhaled allergen or the systemic administration of at least one drug to the body of a human or mammal.

The application belongs to the technical field of biological medicine, and particularly relates to an N-carbonyl-substituted sulfur-containing fused pyrimidinone derivative based on XAV939 as well as a synthesis method and application thereof. The application provides a compound structure with a sulfur-containing fused pyrimidinone skeleton. The application introduces a carbonyl substituent at a specific nitrogen site of a parent nucleus, effectively improves pharmacokinetic properties of the compound XAV939, improves blood-brain barrier permeability, and realizes systemic administration. In addition, the application has a high bioavailability, and can be used for treating autism spectrum disorders. Shank3b In mutant autism model mice, the N-carbonyl-substituted sulfur-containing fused pyrimidinone derivative based on XAV939 first proposed by the application can significantly inhibit Wnt-glycolysis signals, improve social barriers, and has no obvious cytotoxicity, thereby providing a new drug selection for treating autism spectrum disorders.

Compositions for intranasal delivery of olanzapine and methods for their use to treat various symptoms of schizophrenia, schizoaffective disorder, and bipolar disorder, such as acute agitation, mania, and mixed episodes. Intranasal olanzapine compositions comprise dodecyl maltoside to improve bioavailability of olanzapine and is administered via nasal mucosa to avoid direct systemic administration.

The invention relates to the fields of therapy and drug delivery. It is based on an unexpected finding that a combination of an oligonucleotide-based medicament with a saponin component comprising a penta-cyclic triterpene saponin of a 12,13-dehydrooleanane aglycone core, not only does not appear to be associated with oligonucleotide medicament-induced nephrotoxic effects after systemic administration in vivo, but also that it allows the oligonucleotide-based medicament to enter and act on its nucleic acid target inside of the kidney cells instead of remaining unproductively trapped in renal subcellular compartments or being eliminated into the urine via the renal glomerular filtration system. In line with this finding, herein disclosed are therapeutic combinations, compositions, and formulations, as well as methods of treatment involving their administration, which comprise an oligonucleotide-based medicament that acts on an intracellular nucleic acid target in the kidney cells and / or in the cells of the spleen, being the other blood filtering organ in addition to the kidney, and a saponin component that enables the effective release of said medicament inside of these cells, thus allowing its use at a much lower and safer dose. The provision of the presented herein therapeutic combinations enables effective modulation of gene expression in the kidney and / or spleen cells and, therefore, it opens not only new treatment options for kidney diseases, in particular those involving inflammation and / or splenomegaly, but also for diseases of other organs which affect or are affected by the pathological processes happening in the kidneys and / or in the spleen, in particular being inflammatory processes.

The present invention provides attenuated immunostimulatory bacteria whose genome is modified to, for example, reduce toxicity and increase anti-tumor activity, such as by increasing accumulation in the tumor microenvironment, particularly in tumor-resident myeloid cells, increasing resistance to complement inactivation, reducing immune cell death, promoting adaptive immunity, and enhancing T cell function. The increase in phagocyte colonization improves delivery of encoded therapeutic products to the tumor microenvironment and into the tumor, and allows for routes of immunostimulatory bacteria administration such as systemic administration.

The present disclosure relates to methods of systemic inhibition of the mitochondrial pyruvate carrier protein comprising systemic administration of a mitochondrial pyruvate carrier inhibitor to a patient. The disclosure further relates to methods of inducing adult stem cell activation in an aged tissue; reducing at least one sign of aging; promoting hair growth; or inhibiting age-induced tumorigenesis, comprising systemically administering to a patient an MFC inhibitor.

The present application relates to the technical field of tumor immunotherapy. The present application provides a responsive antigen capture nano platform, a preparation method and application thereof. The product of the present application is applied by systemic administration such as intravenous injection; can specifically respond to peroxynitrite in the tumor microenvironment, realize the precise activation of the tumor site; can covalently capture tumor-related antigens through high efficiency, deliver the antigens to antigen presenting cells, so as to enhance the anti-tumor immune response; combined with photodynamic therapy can significantly inhibit tumor growth.

The patent application discloses a liposome nanoparticle of a CTSB inhibitor encapsulated with a PD-L1 targeting agent and a preparation method thereof, and the technology is realized by a liposome of the CTSB inhibitor encapsulated with a PD-L1 targeting agent, the liposome nanoparticle of the CTSB inhibitor encapsulated with the PD-L1 targeting agent comprises a lipid bilayer carrier, a CTSB inhibitor encapsulated in the lipid bilayer carrier, and a PD-L1 targeting modification component modified on the surface of the lipid bilayer carrier; and the average hydration particle size of the liposome nanoparticle is 100-200 nm. The liposome nanoparticle of the CTSB inhibitor encapsulated with the PD-L1 targeting agent can simultaneously realize precise targeted delivery of GBM tumor cells, efficient inhibition of CTSB, down-regulation of PD-L1 expression and remodeling of the tumor immune microenvironment, significantly improve the efficacy of GBM immunotherapy, and at the same time, reduce the toxic side effects of systemic administration.

The invention discloses a preparation method of an IL11 siRNA (at) EVs multi-stage stent and application of the IL11 siRNA (at) EVs multi-stage stent in preparation of kidney defect repair products, and belongs to the technical field of medicine products. By combining ultracentrifugation with an electroporation technology, IL11 siRNA is efficiently loaded in the stem cell-derived extracellular vesicles, and the encapsulation efficiency is high. GelMA / HAMA is used as biological ink, Alg fibers are added, elution is performed after 3D printing, and the macroscopic and microchannel communicated multistage channel network stent is constructed. The stent simulates a kidney structure, the mechanical property is matched with that of a natural kidney, and compared with a traditional hydrogel stent, cell infiltration and neovascularization are effectively guided. The channel structure and mechanical properties of the multi-stage stent prepared by simple physical mixing and DLP 3D printing are not affected, and IL11 siRNA (at) EVs are uniformly distributed in the stent and can be continuously released in the damaged kidney for more than 14 days. Compared with systemic administration, the stent has the advantages that renal injury and fibrosis after partial renal resection can be remarkably relieved, endogenous repair is accelerated, and an ideal scheme is provided for repair after partial renal resection.