182 results about "Membrane vesicle" patented technology

The present invention generally relates to the field of pharmaceutical sciences. More specifically, the present invention includes apparatus and devices for the preparation of pharmaceutical formulations containing large diameter synthetic membrane vesicles, such as multivesicular liposomes, methods for preparing such formulations, and the use of specific formulations for therapeutic treatment of subjects in need thereof. Formation and use of the pharmaceutical formulations containing large diameter synthetic membrane vesicles produced by using the apparatus and devices for therapeutic treatment of subjects in need thereof is also contemplated.

A small number of defined antigens can provide broad protection against meningococcal infection, and the invention provides a composition which, after administration to a subject, is able to induce an antibody response in that subject, wherein the antibody response is bactericidal against two or three of hypervirulent lineages A4, ET 5 and lineage 3 of N. meningitidis serogroup B. Rather than consisting of a single antigen, the composition comprises a mixture of 10 or fewer purified antigens, and should not include complex or undefined mixtures of antigens such as outer membrane vesicles. Five protein antigens are used in particular: (1) a ‘NadA’ protein; (2) a ‘741’ protein; (3) a ‘936’ protein; (4) a ‘953’ protein; and (5) a ‘287’ protein.

A composition comprising (a) Neisseria meningitidis serogroup B outer membrane vesicles (OMVs), and (b) an immunogenic component selected from other Neisseria proteins, or immunogenic fragments thereof. Component (b) preferably includes a protein from a different NmB strain from that from which the OMV of component (a) is derived. The OMVs are preferably obtained by deoxycholate extraction. Optionally, the composition may also comprise a protective antigen against other pathogens.

Outer-membrane vesicles, Class 1 outer membrane proteins of Neisseria meningitidis, fragments or oligopeptides containing epitopes of the Class I OMP can be used to immunize against meningococcal disease.

A composition is prepared from a mixture of different vesicles, such as outer membrane vesicles (OMVs) and vaccines are based thereon. Another composition comprises in a single vesicle a combination of antigens and / or other vesicle components deriving from separate vesicles; again vaccines are prepared therefrom.

The present invention relates to the field of vaccine formulation, particularly the field of novel adjuvant compositions comprising outer membrane vesicles (or blebs), and advantageous methods of detoxifying these compositions, and advantageous methods of use of such adjuvants.

The combination of amlodipine with atorvastatin metabolite shows a synergistic antioxidant effect on lipid peroxidation in human low-density lipoproteins and membrane vesicles enriched with polyunsaturated fatty acids. Inhibition of oxy-radical damage by this drug combination was observed at therapeutic levels in a manner that could not be reproduced by the combination of amlodipine with other statins or the natural antioxidant, vitamin E. The basis for this potent activity is attributed to the chemical structures of these compounds and their molecular interactions with phospholipid molecules, as determined by x-ray diffraction analyses. This combination therapy can be used to treat cardiovascular disorders, especially coronary artery disease, by increasing the resistance of low-density lipoproteins and vascular cell membranes against oxidative modification.

PSA is delivered to the host by outer membrane vesicles (OMVs), secretion structures that target bacterial molecules to host cells. Purified OMVs direct the in vitro differentiation of functional Tregs with potent suppressive activity in a PSA dependent manner. Treatment of animals with OMVs containing PSA prevents experimental colitis and suppresses pro-inflammatory cytokine responses in the gut, and indicate that compositions, medicaments, and methods useful for the treatment of inflammation, and more particularly, inflammatory bowel diseases.

Existing methods of meningococcal OMV preparation involve the use of detergent during disruption of the bacterial membrane. According to the invention, membrane disruption is performed substantially in the absence of detergent. The resulting OMVs which retain important bacterial immunogenic components, particularly (i) the protective NspA surface protein, (ii) protein NMB2132 and (iii) protein NMB 1870. A Typical process involves the following steps: (a) treating bacterial cells in the substantial absence of detergent; (b) centrifuging the composition from step (a) to separate the outer membrane vesicles from treated cells and cell debris, and collecting the supernatant; (c) performing a high speed centrifugation of the supernatant from step (b) and collecting the outer membrane vesicles in a pellet; (d) re-dispersing the pellet from step (c) in a buffer; (e) performing a second high speed centrifugation in accordance with step (c), collecting the outer membrane vesicles in a pellet; (f) re-dispersing the pellet from step (e) in an aqueous medium.

Provided herein are methods and compositions for treating a subject in need thereof comprising administering an effective amount of vesicles with functional transmembrane proteins embedded in the plasma membrane. Also provided herein are methods of restoring gap junctional communication comprising the administration of an effective amount of vesicles.

The invention discloses a preparation method and a drug carrying method of an escherichia coli outer membrane vesicle, and application of the outer membrane vesicle in anti-tumor. The preparation method of the escherichia coli outer membrane vesicle comprises the following steps of culturing a culture medium using LB in vitro, culturing an escherichia coli BL21 strain, performing centrifugation, filtration and ultrafiltration treatment to obtain an upper layer culture solution free of escherichia coli, and finally centrifuging the upper layer culture solution by a supercentrifuge to prepare the escherichia coli outer membrane vesicle. The particle size of the prepared escherichia coli outer membrane vesicle is uniform, and is about 50nm. Usually, a bacterium outer membrane vesicle is low in yield and difficult in drug carrying. The invention excogitates a novel drug carrying method for the bacterium outer membrane vesicle, so that the carrying efficiency of an anti-tumor drug can be significantly improved; an inhibition effect on multiplication and invasion of a tumor cell is increased; and a good application prospect of the bacterium outer membrane vesicle serving as a novel non-virus drug carrier is presented.

The present invention relates to an antigen presenting membrane vesicle comprising on its surface a composition of either relevant molecules for antigen-specific activation or deactivation of T lymphocytes and which is present in the form of an artificially induced lipid vesicle budded from a plasma membrane of a eukaryotic, preferably human, cell, and wherein the composition of said relevant molecules for activation or deactivation present on the vesicle surface is adjustable to a recipient's needs or requirements independently of any blood or tissue cells of said recipient. The invention further relates to a method of manufacture of the vesicles and to compositions containing the vesicles as well as to the use of the vesicles for various purposes including medical and diagnostic applications.

Microvesicles are small membrane vesicles that either shed or bud off eukarotic cells. Analysis of the nucleic acid content of microvesicles may be useful in detecting the presence or absence of genetic aberrations. This invention discloses novel methods of diagnosing, prognosing, monitoring, or treating a disease, such as cancer, or other medical condition in a subject involving analyzing one or more nucleic acids contained within an isolated microvesicle for the presence or absence of one or more Kras genetic aberrations.

The present invention provides an outer membrane vesicle (OMV) from a Gram-negative bacterium, comprising at least one heterologous protein that is free in the lumen of the OMV, wherein the OMV is capable of eliciting an immune response to the heterologous protein when administered to a mammal. The invention also provides methods for preparing the OMVs of the invention, pharmaceutical compositions comprising the OMVs of the invention, especially immunogenic compositions and vaccines, and methods of generating an antibody immune response in a mammal using OMVs.

The present invention relates to methods of preparing biological material, for use in various experimental, diagnostic or therapeutic uses, including immunotherapy treatment or prophylaxy of tumors. More particularly, the present invention relates to methods of preparing membrane vesicles (in particular exosomes) released by various types of mammalian cells, comprising diafiltration and / or density cushion centrifugation. The invention also provides novel methods for characterizing and analyzing exosome preparations, which can be used in quality control assay for the purpose of pharmaceutical product production. The invention is suitable to produce pharmaceutical grade preparations of such membrane vesicles and to fully characterize said preparations, for use in human beings.

The present invention discloses a Gram negative bacterium in which the expression of a protein involved in LPS transport to the outer membrane is functionally downregulated such that the level of LPS in the outer membrane is decreased compared to a wild-type Gram negative bacterium. Down regulation of Imp and MsbA proteins can result in such a bacterium. Outer membrane vesicle preparations derived from the Gram negative bacterium of the invention can be used in vaccines to provide protection against bacterial infection.

In place of a step of centrifugation during preparation of outer membrane vesicles (OMVs) from bacteria, the invention utilises ultrafiltration. This allows much larger amounts of OMV-containing supernatant to be processed in a much shorter time. Thus the invention provides a process for preparing bacterial OMVs, comprising a step of ultrafiltration. The ultrafiltration step is performed on an aqueous suspension of OMVs after they have been prepared from bacteria and the OMVs remain in suspension after the filtration step. The invention is particularly useful for preparing OMVs from Neisseria meningitidis.

The present technology provides vaccine compositions comprising native outer membrane vesicles (NOMVs) from at least one genetically modified strain of Neisseria which provides protective immunity to meningococcal disease, more preferably subtype B meningococcal disease. The present technology further provides methods of immunizing an animal or human against meningococcal disease comprising administering the vaccine composition of the present invention.

The invention relates to a preparation method and application of macrophage membrane bionic bismuth selenide nanoparticles. The preparation problem of macrophage membrane bionic bismuth selenide nanoparticles and the application problem in preparing bionic anti-tumor drugs and photothermal treatment drugs based on cell membrane wrapping can be effectively solved. According to the technical scheme,the surface of hollow bismuth selenide nanoparticles is physically loaded with an anti-tumor drug quercetin, and then the hollow bismuth selenide nanoparticles with the quercetin is co-extruded withcell membrane vesicles obtained by low-permeability lysis solution pyrolysis treatment of cells and homogenization, so as to obtain a pharmaceutical composition of the cell membrane bionic bismuth selenide nanoparticles with a particle size of 120-150nm. The preparation process is simple and feasible; the particle size distribution is uniform; the sensitivity of cancer cell to light and heat is enhanced, and the anti-tumor effect of photothermal therapy is enhanced; the macrophage membrane bionic bismuth selenide nanoparticles have multiple functions such as metastatic lesions targeting capability, CT imaging and the like; and the anti-tumor efficacy of the drug is improved.

The invention relates to a targeting atherosclerotic focus cell membrane bionic drug-delivery system preparation method and a product and an application thereof. The method comprises the following steps: extracting a macrophage membrane, repeatedly extruding the macrophage membrane to prepare macrophage membrane vesicle, then mixing the material with polylactic acid-glycolic acid copolymer nanoparticles, and repeatedly extruding a filter membrane to prepare a spherical drug-delivery system. The system has an obvious core / shell structure, an average particle size is 167+ / -6.12 nm, and alpha4beta1 integrin is kept on the surface; a VCAM-1 acceptor can be effectively identified, and the system can present good in-vitro and vivo targeting, and is expected to be used for treating atherosclerosis and related diseases.

Outer-membrane vesicles, Class 1 outer membrane proteins of Neisseria meningitidis, fragments or oligopeptides containing epitopes of the Class I OMP can be used to immunize against meningococcal disease.

An immunoniosmes for targeted delivery of therapeutic agents to specific tissues in a host and methods of synthesis of those niosomes. An antibody molecule having specificity for a target antigen, such as a cell surface marker or other marker differentially expressed on a target cell, is covalently coupled to a functionalized membrane constituent. In a particular embodiment the functionalized membrane constituent is polyoxyethylene sorbitan monostearate functionalized with cyanuric chloride. The niosomes of this invention thus provide a composition that enhances internalization or retention of the bioactive agent of the niosome into the cytoplasm of the cells of the target tissue by providing a high degree of target specificity. Furthermore, the membrane vesicle enhances the life of the therapeutic agent by preventing its degradation in the extracellular environment, while exhibiting lower toxicity than can occur with some liposomes. The niosomes of the present invention are thus particularly useful as vehicles for the delivery of therapeutics to specific target cells.

Method for the insertion of protein antigens, of recombinant or synthetic origin, in outer membrane vesicles of Gram-negative bacteria without disruption of the vesicle structure, therefore maintaining the immunogenicity and immunostimulatory properties of said vesicles, and with the reported advantage that the immune response generated against the incorporated antigen is superior to the one generated when the antigen is administered alone. The resultant vaccine formulations are useful to increase protective capacity of existing vaccines and allow to extend it against different pathogens, in diseases of bacterial, viral, cancerous or other etiology. The referred formulations are applicable in the pharmaceutical industry as vaccines for therapeutic and preventive use in humans.

OMVs targeted against specific epidemic strains can be highly effective in controlling localised outbreaks of disease. In combination with large-scale and reproducible manufacturing techniques, a vaccine can be rapidly produced after an outbreak. The invention provides a method for preparing a meningococcal outer membrane vesicle (OMV) vaccine, comprising the steps of: (i) identifying the serosubtype of a meningococcal strain associated with an outbreak of meningococcal meningitis; (ii) preparing OMVs from a meningococcal strain having the serosubtype identified in step (i) for use in vaccine manufacture. The method may comprise one or both of the further steps of (iii) formulating said OMVs as a vaccine; and (iv) distributing said vaccine in a geographical area affected by or likely to be affected by said outbreak. The meningococcal strain will typically be in serogroup B, but may be instead by in serogroup A, C, W135, Y, etc.

The present invention provides a method of immunizing a subject against a disease caused by Neisseria meningitidis, comprising administering to the subject a primer composition comprising a meningococcal outer membrane vesicle preparation, and a booster composition comprising a meningococcal protein antigen preparation. Vaccine combinations comprising primer and booster compositions and associated uses are also provided.

The invention discloses a preparation method of a nano medicine controlled release system. The preparation method comprises the following steps: (1) preparing a nanoscale red blood cell membrane vesicle, (2) preparing photosensitive drug-loaded graphite oxide, (3) preparing a target molecule and (4) preparing the nano drug controlled release system. According to the method, a protein crown of a nano carrier due to coating by certain in-vivo proteins can be avoided by embedding of a red blood cell vesicle; the activity of the target molecule is guaranteed; the red blood cell membrane vesicle exists in a human body, has good biocompatibility and no toxic and / or side effects and does not cause a rejection reaction; the red blood cell embedded vesicle can effectively reduce surface free energyof graphite oxide and improve dispersity of the nano drug controlled release system; graphite oxide is absorbed with a photosensitizer, namely indocyanine green; and together with photo-thermal treatment, an antitumor effect of the nano drug controlled release system can be further improved.

The invention discloses a platelet membrane self-assembly nanobubble, and a preparation method and application thereof. The preparation process includes the following steps: (1) performing repeated freezing and thawing on platelets, and obtaining purified platelet membrane vesicle suspension through washing; and performing homogenization through a water bath ultrasonic effect; and (2) realizing the self-assembly and reorganization of platelet membrane fragments on a gas-liquid interface after the ultrasonic cavitation fragmentation or gas-liquid mixing repeated extrusion of the homogenized platelet membrane vesicle suspension so that the platelet membrane coated nanobubble can be constructed and formed. The preparation method of the nanobubble is simple; and the nanobubble with a nano sizeand reserving the natural properties of the platelet membranes has high biocompatibility and vascular injury targeting, and can be used for the ultrasound imaging diagnosis of vascular injury parts,and therefore, the problems of difficult targeted ultrasound imaging diagnosis of early small micro-lesions of cardio-cerebrovascular diseases can be solved.