56 results about "Systemic administration" patented technology

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.

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.

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.

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.

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 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.

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 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 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 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.

Disclosed is a drug for preventing and treating diseases related to abnormal intestinal hyperplasia. Specifically disclosed is the following: The accumulation of myeloid-derived inhibitory cells (MDSCs) caused by the reduction of IL-10 is the main cause of abnormal hyperplasia of the intestinal epithelium, and supplementation of IL-10 within myeloid cells at the source helps to restore bone marrow microenvironment homeostasis and reduce the production of pathogenic MDSCs, thereby treating diseases related to abnormal hyperplasia of the intestinal epithelium, such as inflammatory bowel disease and adenomatous polyposis. Disclosed is a recombinant adeno-associated virus vector expressing IL-10. Targeted delivery of IL-10 to myeloid cells is achieved by means of intraosseous injection, avoiding adverse effects caused by systemic administration. This approach offers targeting specificity and safety and provides a new solution for the treatment of diseases related to abnormal intestinal hyperplasia.

The application relates to the field of biological medicine, in particular to a medicine for preventing intimal hyperplasia and application thereof, and specifically discloses application of a plasmid in preparation of a medicine for preventing intimal hyperplasia through extra-vascular injection, wherein the plasmid is one or more of HGF plasmid, VEGF plasmid and eNOS plasmid, and the plasmid is a naked plasmid. Through the scheme, a medicine of a safe, simple, efficient and local continuous expression gene delivery mode is developed, the medicine is precisely delivered from outside to inside through an extra-vascular injection path, the problems of easy loss of intraluminal medicine and poor targeting of systemic administration are solved, and the treatment effect of the disease is greatly improved.

According to the multi-component synergistic 3D printing multi-structure long-acting anti-infection bone repair composite scaffold and the preparation method thereof, the method comprises the following steps: preparing a PVA aqueous solution as a slurry adhesive, and mixing HA, beta-TCP, the PVA aqueous solution and glycerol as a printing slurry; 3D printing parameters are set, a model is imported, a printing structure, discharging and wiring speeds are set, and a customized support is obtained through 3D printing; drying and sintering the scaffold to obtain a porous bone scaffold without organic matters; preparing porous microspheres ABX coated PLGA loaded with antibiotics by taking gelatin as a pore-foaming agent; and coating the sintered porous bone scaffold with a gelatin coating, and loading the microspheres on the porous bone scaffold to obtain the drug-loaded composite bone scaffold. The bone repair scaffold disclosed by the invention is combined with an antibiotic local drug delivery system to prevent infectious bone defects, can overcome the defects of systemic drug delivery of antibiotics, realizes controllable release of drugs in the whole process in a bone regeneration period, has good antibacterial performance while repairing bone defects in vivo, and also has relatively good compressive strength and biocompatibility.

The present disclosure relates to polymeric compositions and methods for activating gamma delta T cells, specifically Vγ9Vδ2 T cells, in cancer immunotherapy. These compositions include a cell-targeting moiety and a polymer incorporating phosphoantigens (pAgs) for targeted delivery to tumor cells. The method involves administering an effective amount of these compositions to a subject, allowing controlled release of pAgs in the tumor microenvironment. This approach overcomes limitations of systemic pAg administration and can be used alone or with adoptive transfer of Vγ9Vδ2 T cells or PBMCs. The treatment may involve repeated administrations and is applicable to various cancer types. This disclosure also covers methods for synthesizing these compositions and their use in cancer treatment applications.

The application belongs to the technical field of biomedical polymer materials, and discloses in-situ nanofiber materials for enhancing tumor immunogenicity, and a preparation method and application thereof. The application constructs in-situ nanofiber loaded with a degradable carrier, a molecular targeted drug Anlotinib and Gep nanosheet, and then the in-situ nanofiber is made into a patch and directly applied to a tumor lesion, and is combined with NIR assisted irradiation and aPD-L1 treatment. The application not only improves the delivery efficiency of AL through local administration, and overcomes the problem of low efficiency of systemic administration through a nanocarrier, but also takes inhibition of excessive growth of HCC blood vessels as a starting point, combines PTT and ICB treatment, and enhances the immunogenicity of a residual tumor after a three-mode combined treatment cascade, and enhances an immune response. Meanwhile, the application has the advantages of simple components, flexible formula, easy preparation and the like. Therefore, the in-situ nanofiber material has wide practical application value in the field of tumor treatment.

This invention relates to novel neurotropic adeno-associated virus (AAV) capsid variants. In particular, the invention relates to novel AAV capsid variants that efficiently transduce cells in the central nervous system (CNS) upon systemic administration, while exhibiting reduced transduction to peripheral organs. The invention further relates to a method for identifying AAV capsid variants having one or more desired properties, such as a combination of CNS targeting and peripheral organ detargeting.

The present disclosure provides methods for treating or alleviating symptoms of a disease, disorder, or condition related to excess androgen or stress-induced skin changes in a subject in need thereof by topically administering a pharmaceutical composition comprising a pharmaceutically effective amount of spironolactone to the subject. Other aspects relate to methods for providing anti-oxidative stress, anti-inflammatory and anti-aging benefits for the skin to a subject in need thereof by topically administering a pharmaceutical composition comprising a pharmaceutically effective amount of spironolactone to the subject. Surprisingly, it has been found that spironolactone may be topically administered with reduced adverse effect compared to systemic administration of the same medication.

The present invention relates to homing peptide-directed decorin conjugates for the treatment of epidermolysis bullosa, and corresponding methods of treatment. The use of novel homing peptides enables the targeting of the conjugates in vivo to specifically home to the skin and skin wounds by systemic administration.

The application discloses a bone inductive active polypeptide capable of being assembled into nanofiber hydrogel and application thereof. The bone inductive active polypeptide comprises an assembly domain at a C terminal, a bone inductive active domain at an N terminal and a flexible connection separation domain between the two. The assembly domain is (RADA) 4‑9 The bone inductive active domain is parathyroid hormone (PTH) or parathyroid hormone related peptide (PTHrP). The bone inductive active polypeptide can be spontaneously assembled into a peptide nanofiber, and can be co-assembled into a peptide nanofiber hydrogel by mixing with RADA16 peptide. The hydrogel assembled from the bone inductive active polypeptide and the high-molecular composite nanobiomaterial constructed by the hydrogel can effectively avoid polypeptide burst release, avoid polypeptide degradation by local proteases, replace long-term systemic systemic administration of PTH and PTHrP, improve patient compliance and reduce patient pain. The application provides a new strategy for in-situ bone repair of PTH and PTHrP.

The invention discloses a small molecule activator targeting nerve cell aromatase and application of the small molecule activator in cerebral ischemia injury, and belongs to the technical field of biological medicine. The activator can directly enhance the catalytic activity of aromatase without significantly affecting the gene transcription of aromatase, so that the local estrogen level in the brain is accurately improved, and the neuroprotection effect is achieved. The neuron aromatase is specifically activated, so that the side effect of systemic estrogen treatment is avoided. In-vivo and in-vitro experiments prove that the concentration of estrogen in a target region can be effectively improved through local intracerebral administration, and the survival rate of neurons in an oxygen-glucose deprivation / reoxygenation injury model is remarkably improved. The pharmaceutical composition provided by the invention is suitable for local administration or systemic administration of a central nervous system, can be combined with the existing therapy, and provides a brand new treatment strategy and drug candidate for cerebral ischemia injury.

The application discloses a preparation method of IL11 siRNA@EVs multistage scaffolds and application thereof in preparation of kidney defect repair products, and belongs to the technical field of pharmaceutical products.The IL11 siRNA is efficiently loaded in stem cell-derived extracellular vesicles by ultracentrifugation combined with electroporation technology, and the encapsulation rate is high.GelMA / HAMA is used as bio-ink, and Alg fibers are added, then the multistage channel network scaffold with macroscopic and microchannel through channels is constructed after 3D printing and elution.The scaffold is bionic kidney structure, and the mechanical properties are matched with the natural kidney.Compared with traditional hydrogel scaffolds, the scaffold can effectively guide cell infiltration and neovascularization.The channel structure and mechanical properties of the multistage scaffold prepared by simple physical mixing and DLP 3D printing are not affected, the IL11 siRNA@EVs are uniformly distributed in the scaffold, and the IL11 siRNA@EVs can be continuously released in the damaged kidney for more than 14 days.Compared with systemic administration, the scaffold can significantly reduce the kidney injury and fibrosis after partial nephrectomy, and accelerate endogenous repair, thereby providing an ideal scheme for postoperative repair after partial nephrectomy.

The invention discloses a tanshinone I intrauterine sustained-release medicament for treating gynecological tumors and application thereof, which is characterized in that tanshinone I is prepared into a nano-structure lipid carrier with the average particle size of 100-200nm, so that the water solubility and biological membrane permeability of the nano-structure lipid carrier are remarkably improved; and then the carrier is loaded in a biodegradable polymer slow-release rod which can be placed in a uterine cavity. The sustained-release rod can release drugs when the environment in the uterine cavity declines, and local, long-acting and targeted drug delivery to the focus part is achieved. An in-vitro cell experiment proves that the inhibiting effect of the preparation on hysteromyoma cells is obviously higher than the toxicity of the preparation on normal hysteromyoma cells, and the selectivity index is greater than 2; therefore, the problems of poor solubility of tanshinone I and weak systemic administration targeting are solved, and the tanshinone I has the outstanding advantages of high efficiency, low toxicity and good patient compliance.

The application provides a method for constructing a local inflammation model of an experimental animal brain, which comprises the following steps: anesthetizing the experimental animal and fixing the experimental animal on a positioning device; injecting an immunomodulator into a target region according to the coordinates of the target region by using a puncture tool; controlling the injection speed and dose of the immunomodulator by using a micro-infusion device; keeping the puncture needle in the body for a period of time after injection to reduce the backflow of the liquid medicine; verifying the local immune activation by quantitatively detecting the expression change of an inflammation marker in the target region, and synchronously detecting the expression level of the inflammation marker in a peripheral medium to exclude a systemic immune response. The application can effectively solve the problem that the peripheral inflammation effect is difficult to distinguish in the research of brain diseases caused by systemic administration in the prior art, and can be applied to the research of the local immune activation effect of diseases such as Alzheimer's disease, ischemic stroke and glioblastoma, and the evaluation of the efficacy and mechanism of STING agonists in these diseases.