128 results about "Immune phagocytosis" patented technology

Methods are provided to manipulate phagocytosis of cancer cells, including e.g. leukemias, solid tumors including carcinomas, etc.

A method of making a pharmaceutical composition containing a drug and solid lipidic microparticles, which are suitable for parenteral administration and resistant to phagocytosis by macrophage, is described.

The invention relates to a liver targeting anticancer nanometer prodrug system basing on dendritic polymer, provides a method for preparing the prodrug system and the uses thereof and belongs to the technical field of biological medicine as well as the technical field of nano medicine. With the polyethylene glycol modified PAMAM treelike polymer of distal liver targeting group (T) as a carrier (T-PEG-PAMAM) and Doxorubicin (DOX) as treatment drug, the invention obtains the prodrug (T-PEG-PAMAM-DOX) through the covalent bond connection with degradable lysosome between the carrier and the Doxorubicin. The invention further provides the application of the liver targeting anticancer nanometer prodrug system basing on the dendritic polymer in the preparation of drugs for treating solid tumors. With the long-acting cycle in blood, the liver targeting anticancer nanometer prodrug system basing on the dendritic polymer can enhance the phagocytosis of hepatoma cells on polymers nano-micelles, realize the active and passive targeting on liver tumor tissues, improve the clinical efficacy and the bioavailability of present liver cancer therapeutic drugs and lower toxic and side effects.

This invention provides pharmaceutical compositions and methods related to the prevention and treatment of primary tumors and metastatic, malignant or spreading cancers by selectively targeting cancer associated myeloid derived cells by the targeted delivery of a bisphosphonate formulated with a non-liposomal particle carrier. In some aspects, the bisphosphonate particles have one or more properties suitable for phagocytosis by cancer associated myeloid derived cells and release of the bisphosphonate within the macrophages. Advantageously, administering the particles to a subject reduces the level and / or activity of cancer associated myeloid derived cells in the subject.

The purpose of the present invention is to provide a diabody-type bispecific antibody, which is characterized by having low immunogenicity and high infiltrating activity into tumor tissues, and by being easily mass-produced at a low cost with use of microorganisms, and by being easily altered in function by means of genetic engineering. The diabody-type bispecific antibody shows a more remarkable effect than the conventional diabody-type bispecific antibodies and chemically synthesized bispecific antibodies even in a very low concentration and in the absence of the super antigen. The present invention is related to a diabody-type bispecific antibody, having a first specificity to a human epidermal growth factor (EGF) receptor and a second specificity to a surface antigen expressed by a cell having phagocytosis or cytotoxic activity, a single-chain polypeptide constituting the antibody or each region contained therein, a nucleic acid encoding the polypeptide, a replicable cloning vector or expression vector comprising the nucleic acid, a host cell transformed with the vector, and a pharmaceutical preparation comprising thereof.

A recombinant bi-functional fusion protein, comprising an Ig region of an extracellular domain of a signal-regulator protein (SIRP), linked via a Fc fragment of an Ig, to an Ig region of an extracellular domain of VEGFR, wherein the protein can bind to CD47 and VEGF simultaneously, blocking the binding of CD47 with the SIRP on the cell surface of macrophages to stimulate the phagocytosis of tumor cells by macrophages, and inhibiting the growth of vascular endothelial cells induced by VEGF. The present application also provides a nucleic acid molecule encoding the recombinant bi-functional fusion protein and an expression vector expressing the protein, a method for producing the protein and a method for treating a disease over-expressing CD47 or VEGF.

The invention belongs to the field of organic synthesis or pharmaceutical preparations and relates to a synthesis method of a hyaluronic acid-photosensitizer / antitumor drug with synergistic anti-tumor efficacy and a preparation method of a nano drug delivery system. Conjugates are amphiphilic by connecting a photosensitizer and an indissolvable antitumor drug on a hyaluronic acid skeleton by ester bonds and are self-assembled in water to obtain a nanomicelle. The synthesis method and the preparation method are characterized by comprising the synthesis method of covalent linkage of hyaluronic acid and a photosensitizer / antitumor drug and a method for self-assembling the nano drug delivery system by the hyaluronic acid-photosensitizer / antitumor drug. The system is expected to have good biocompatibility and active targeting property of tumors in a body; the solubility of the indissolvable antitumor drug can be improved, the phagocytosis of a reticuloendothelial system is avoided, and the cycle time in the body is prolonged; after the system reaches a lesion location, the ester bonds of the system are fractured in a tumor microenvironment under the condition of a low pH value and releases the photosensitizer and the antitumor drug; the system is excited by near-infrared light to generate heat and fluorescence; on one hand, tumor cells are killed and wounded by a phototherapy and chemotherapy combined mode; on the other hand, distribution conditions of the tumor cells in the body can be characterized.

The present invention encompasses monoclonal antibodies that bind to lipoteichoic acid (LTA) of Gram positive bacteria. The antibodies also bind to whole bacteria and enhance phagocytosis and killing of the bacteria in vitro. The invention also provides antibodies having human sequences (chimeric, humanized and human antibodies). The invention also sets forth the variable regions of three antibodies within the invention and presents the striking homology between them.

The invention relates to a tumor vessel-tumor cell membrane-cell nucleus continuous targeted drug delivery system, as well as a preparation method and application thereof. The tumor vessel-tumor cell membrane-cell nucleus continuous targeted drug delivery system comprises mesoporous silica nano-particles, RGD polypeptide which is linked to the surfaces of the mesoporous silica nano-particles in a covalent manner and serves as a tumor vessel / tumor cell membrane targeting ligand, and a nuclear localization signal polypeptide sequence serving as a cell nucleus targeting ligand. Under the condition of intravenous injection, the drug-loaded system can be enriched in a tumor tissue by means of the targeting effect of the tumor vessel to reduce the uptake of normal tissues and reduce toxic and side effect, is capable of increasing the phagocytosis amount of tumor cells by means of the identification effect on the tumor cell membrane, and can be used for directly delivering anti-cancer drugs into a cell nucleus by means of the delivery performance of the cell nucleus to increase the concentration of effective drugs, so that an optimal treatment effect can be achieved.

A new class of pH sensitive fluorescent dyes and assays relating thereto are described. The dyes and assays are particularly suited for biological applications including phagocytosis and monitoring intracellular processes. The pH sensitive fluorescent dyes of the present invention include compounds of Formula I:wherein the variables are described throughout the application.

This invention describes a novel, two-step method for administering PFC. The first step is designed to block the RES by administration of empty, small, liposomal vesicles (ESV) that are rapidly and preferentially engulfed by macrophages, thereby inhibiting their phagocytosis of subsequently infused PFC emulsions. The second step is the subsequent injection of PFC. ESV are devoid of materials that interfere with the macrophage's metabolic processes and do not impair their ability to clear the circulation of pathogenic organisms. Inhibition of the removal of PFC from the blood stream by the RES will achieve increased circulating PFC, enhanced binding and transport of oxygen throughout the blood stream and consequential reduction of undesirable consequences such as organomegaly and cytokine toxicity.

The invention provides intravenous nanomicelle agents of vinca alkaloids antitumor drug, it contains an effective dose for treating of vinca alkaloids antitumor drug (vinblastine and vincristine or vindesine), macrogol derivatization phospholipid, and the pharmaceutical acceptable adjuvants. Its preparation is to pack the drug in the formative nanomicelle agents, prepare and make the intravenous nanomicelle agents of vinca alkaloids antitumor drug. Vinca alkaloids antitumor drug and macrogol derivatization phospholipid form into a very uniform size nanomicelle. In micelles, polyethylene glycol molecule and hydrophobic core for drug packing form a hydrophilicitious inhibitory coating, avoid the drugs contact with the protein such as enzymes in the blood and identified and phagocytized by the endothelial system in vivo, phagocytosis, the cycle time of micellar in vivo is extended. In addition, the micellar drug also increases the storage stability and the effect on the tumor of the drug and reduces drug toxicity.

The invention discloses an amphiphilic camptothecin polymer prodrug taking phenylboronic acid ester as a connecting unit and a co-delivery micelle system thereof. A polyethylene glycol-polyglutamate camptothecin two-block polymer (mPEG-BC-PGluCPT) is synthesized by taking catechol phenylborate (BC) as a connecting unit, and then a doxorubicin loaded micelle (mPEG-BC@PGluCPT.Dox) of the polymer isconstructed. Aiming at the poor water solubility of camptothecin, a polymer prodrug using camptothecin as a hydrophobic end by modifying 20 sites of hydroxyl groups of camptothecin is synthesized, which can effectively promote the assembly of the two-block polymer into a micelle. The solubility of camptothecin is improved, the stability of a camptothecin lactone ring is increased, and the curativeeffect and bioavailability are improved in order to overcome limitations of clinical treatment of camptothecin. The amphiphilic camptothecin polymer prodrug prepared by the method provided by the invention can be used for constructing a nano drug common delivery system, and has good drug release property, strong cell inhibition rate and good cell phagocytosis.

Swellable particles for delivery of a drug or other working agent to the pulmonary system are provided. The swellable particles include a dehydrated (dry) aerodynamic particle diameter of 5 μm or less to enable delivery to the respiratory tract, such as for example to the tracheo-bronchial airways of the upper respiratory tract and / or to the alveolic regions of the deep lung, and a hydrated particle diameter that is greater than 6 μm volume mean diameter to retard or prevent their phagocytosis by the macrophages present in airways of the respiratory tract.

The invention relates to a liver-targeting intelligent nano-micelle prodrug system based on polyethylene imine, and provides a method for preparing a macromolecular prodrug. The low-toxicity polyethylene imine modified by polyethylene glycol with a liver-targeting group (T) at the remote end is used as a carrier (T-PEG-PEI), adriamycin (ADR) is used as a treatment medicament, and the carrier is connected with the adriamycin through a lysosome degradable covalent bond to form a prodrug (T-PEG-PEI-ADR). The T-PEG-PEI-ADR prodrug is self-assembled into micelles with grain diameter being 10 to 500 nanometers in water solution. The micelle prodrug system can circulate with long effect in blood, strengthen the phagocytosis of liver cancer cells on polymer nano-micelle, selectively deliver the treatment medicament to the liver tumor part, directionally kill the liver tumor cells, reduce the toxic and side effects of the adriamycin on treating the liver caner, and improve the clinical efficacy and bioavailability of the prior liver cancer treatment medicament.

The invention discloses a diblock polymer with benzeneboronic acid ester as the connecting unit. Benzeneboronic acid catechol ester (BC) is adopted as the connecting unit to synthesize PEG-BC-PBLG diblock polymer so as to construct doxorubicin loaded micelle (PEG-BC@PBLG.Dox). The invention also discloses a preparation method of the diblock polymer, and the method includes: (1) preparing the dopa derivative PEG-3, 4-DA of PEG-NH2; (2) subjecting PEG-3, 4-DA and 3-aminophenylboronic acid to dehydration condensation so as to synthesize the benzeneboronic acid ester derivative PEG-BC of PEG; and (3) using PEG-BC to perform ring opening on 5-benzyl ester-L-glutamic acid-N-carboxyanhydride (BLG-NCA), thus obtaining the diblock polymer PEG-BC-PBLG with benzeneboronic acid ester as the connecting unit. The diblock polymer prepared by the method provided by the invention can be used for construction of a nano-micelle, and has the advantages of good drug release, low cytotoxicity and good cell phagocytosis.

The invention provides a paclitaxel polymer bonding drug comprising a carboxyl end group contained polymer and paclitaxel esterified and bonded together with the carboxyl end group contained polymer. A preparation method of the carboxyl end group contained polymer comprises the steps of subjecting an aliphatic cyclic ester monomer to ring opening polymerization under the action of a catalyst by taking methoxy polyethylene glycol or polyethylene glycol as an initiator to obtain an amphiphilic polymer; subjecting the amphiphilic polymer and disulfide bond contained diacid to reaction in a first organic solvent under the action of organic alkaline and a condensing agent to obtain the carboxyl end group contained polymer. The solubility of paclitaxel in water can be increased by using the paclitaxel polymer bonding drug; the paclitaxel polymer bonding drug has reduction sensibility so as to be capable of being self-assembled to form a micelle; the paclitaxel polymer bonding drug has favorable hydrophilicity and biocompatibility, so that human reticuloendothelial system phagocytosis in blood circulation can be avoided, and the paclitaxel polymer bonding drug has sufficient time to reach a cancer position through an EPR (Enhanced Permeability and Retention) effect and further enters cells through endocytosis, thus an efficient targeting effect of the drug is achieved.

The invention discloses a health product for improving bone density and immunity, which active ingredients have the following weight ratios: 60-140 radix puerariae extract, 120-280 D-dextrosamine and 120-280 calcium. The advantages of the health product in the invention are in that: rapid releasing, easy for absorbing, improving arthrosis pain caused by bone loss, preventing and treating various diseases caused by cartilage tissue cataplasia; distinctly increasing ingestion action of liver and spleen macrophage to ingest carbon granules, distinctly accelerating lymphocyte transformation and raising phagocytosis rate of the macrophage to obviously improve nonspecific immunity function of human body. Accordingly, the invention has good and fast effect for increasing bone density and immunity.

The invention belongs to the field of a drug preparation, and relates to a docetaxel nanometer lipid carrier and a preparation method. The docetaxel nanometer lipid carrier basically comprises docetaxel, solid state lipid materials, liquid oil, an emulsifier, PEG-modified ester and injection water which are of therapy effective dose. The docetaxel nanometer lipid carrier has stable docetaxel structure, is beneficial to avoiding phagocytosis of reticuloendothelial system in a body, and can be stably stored.

The invention discloses a microecological modulator. The microecological modulator is prepared from photosynthetic bacteria, actinomycetes, bacillus, saccharomycetes, lactic acid bacteria, nitrogen-fixing bacteria, phosphate-solubilizing bacteria, potassium bacteria, silicate bacteria, bacillus radicicola, blue-green algae, vitamin C, nitrogen, boron, iron, saccharose, calcium sulfate, dipotassium phosphate, calcium carbonate, magnesium sulfate, sodium chloride and agar. According to the microecological modulator disclosed by the invention, by adopting a fusion technique of multiple useful microbiological populations, the useful microbiological population and plant enzymes are fermented and cultivated at the same time, mutual phagocytosis of biological populations in a fusion process of the biological populations can be prevented, and symbiosis and compatibility are realized. The microecological modulator disclosed by the invention is rich in multiple microbiological populations and multiple trace elements and mineral substances needed by plant growth, so that microecological circulation of soil can be improved, and the fertilizer efficiency of the soil is enhanced; the microecological modulator replaces chemical fertilizer; photosynthesis of leaf surfaces of plants and crops is enhanced, the oxidation is reduced, and leaf surfaces of the plants and the crops can be lustrous and plump; the plants and the crops can be full in fruits; the yields of the plants and the crops can be increased.

The invention relates to an aeromonas hydrophila micro-capsular oral vaccine, which belongs to the technical field of biological pharmacy. The aeromonas hydrophila micro-capsular oral vaccine is prepared by using sodium alga acid and chitosan as wall materials, using the inactivated bacteria of aeromonas hydrophila as a core material and by using improved atomization and ion crosslinking technology. When the aeromonas hydrophila sodium alga acid-chitosan micro-capsular oral vaccine is used for immunizing a mouse and crucian, the phagocytosis activities of macrophages, the conversion efficiency of the splenic lymphocytes and the expression amount of cell factors such as IFN-gamma and Il-4 of the mouse and the crucian can be improved obviously. The relative protection rate of the vaccine for the crucian is 39.3 percent. A microcapsule is stable in a simulated gastrointestinal environment and shows high burst release and slow release; and the bacterial antigenicity of the microcapsule is well maintained and the vaccine has high safety and high storage stability.

Provided are monoclonal antibodies and antigen-binding fragments thereof that bind to CD47 of multiple mammalian species, block the binding of SIRPalpha and TSP1 to CD47, promote phagocytosis of susceptible cancer cells, and reverse TSP1 inhibition of nitric oxide signaling, as well as monoclonal antibodies and antigen binding fragments thereof that compete with the former for binding to CD47 and that exhibit similar biological activities. Also provided are combinations of any of the foregoing. Such antibody compounds are variously effective in 1) treating tissue ischemia and ischemia-reperfusion injury (IRI) in the setting of organ preservation and transplantation, pulmonary hypertension, sickle cell disease, myocardial infarction, stroke, and other instances of surgery and / or trauma in which IRI is a component of pathogenesis; 2) in treating autoimmune and inflammatory diseases; and 3) as anti-cancer agents for treating susceptible cancer cells, promoting their phagocytic uptake and clearance.

Embodiments provide devices, systems and methods for the transdermal delivery of chelated compounds. One embodiment provides a method for the iontophoretic transdermal delivery of a chelated iron complex for the treatment of anemia. A first patch comprising an active electrode and a chelated iron complex is applied to the skin; a second patch containing an electrode is also applied. An electrical current is then delivered to the skin from the active electrode. The chelated complex is transported across the skin via electromotive force from the current, with the iron being substantially chromogenically unreactive with the skin during transport so that there is little or no tattooing of the skin due to the formation of insoluble oxidative products. The complex is then dissociated by phagocytosis or related process to release the iron where it may be bound by transferrin or ferritin and carried to other sites for storage or metabolic use.

The invention relates to a preparation method of an autophagy-imitated immune cell supported antitumor therapeutic agent. The preparation method comprises steps as follows: an antitumor therapeutic agent, cell membranes and immune cells are taken as raw materials, immune cell membranes are extracted to encapsulate the antitumor therapeutic agent, nano-particles containing apoptosis groups are co-cultured with the immune cells after being formed, the nano-particles are phagocytized by the immune cells, the antitumor therapeutic agent is enabled to be indirectly encapsulated into the immune cells, and the autophagy-imitated immune cell supported antitumor therapeutic agent is prepared. Compared with the prior art, the antitumor therapeutic agent is encapsulated with the cell membranes containing the apoptosis groups, the phagocytosis quantity of the antitumor therapeutic agent by the immune cells is increased, cell carriers meeting various demands are prepared, the problems of irregularrelease and low phagocytosis quantity of the therapeutic agent due to adoption of a traditional supporting method are solved, and meanwhile, toxicity of drugs for the cell carriers is reduced.

The present invention is directed to protocells, which have a core and a lipid bilayer surrounding the core, with at least one CD47 molecule or an active fragment thereof in or conjugated to the lipid bilayer. The CD47 present on the lipid bilayer allows the protocell to evade phagocytosis by macrophages, and can be conjugated to the lipid bilayer via a crosslinker. The protocell can be loaded with a diagnostic or therapeutic cargo, such as a polypeptide, a nucleic acid, or a drug. The protocell can also include a targeting species for targeted delivery of the cargo to a cell. The protocell can also include an endosomolytic peptide, which promotes endosomal escape after uptake by the targeted cell. The protocells with CD47 on the lipid bilayer provide better circulation after in vivo administration compared to protocells without CD47, and are therefore particularly useful as a cargo delivery vehicle.

Anthracyclin-treated turn or cells are particularly effective in eliciting an anti-cancer immune response, where the rDNA-damaging agents, such as etoposide and mitomycin C do not induce immunogenic cell death. Anthracyclins induce the rapid, pre-apoptotic translocation of calreticulin (CRT) to the cell surface. Blockade or knock down of CRT suppressed the phagocytosis of anthracyclin-treated tumor cells by dendritic cells and abolished their immunogenicity in mammals, such as mice. The anthracyclin-induced CRT translocation was mimicked by inhibition of the protein phosphatase1 / GADD34 complex. Administration of recombinant CRT or inhibitors of protein phosphatase1 / GADD34 restored the immunogenicity of cell death elicited by etoposide and mitomycin C, and enhanced their antitumor effects in vivo. These data identify CRT as a key feature determining anti-cancer immune responses and delineate a possible strategy for immunogenic chemotherapy.

A method for preparing berberine hydrochloride composite nanoparticles comprise the following steps: (1) preparing berberine hydrochloride composite nanoparticle; (2) preparing berberine hydrochloridecomposite nanoparticles; as the only active ingredient, the berberine hydrochloride composite nanoparticles prepared by the invention can inhibit MCF-7 cell drugs; the berberine hydrochloride composite nanoparticles prepared by the invention are used as the only active ingredient in preparing anti-staphylococcus aureus and anti-escherichia coli medicines. The above preparation method is simple, the prepared composite nanoparticles have uniform particle size, encapsulation efficiency is high, which can reduce the recognition and phagocytosis of reticuloendothelial phagocytosis system (RES), and has slow release effect, increase the long circulation of carrier in vivo, improve the biological activity of drug, and achieve high efficiency and low toxicity, which provides conditions for the clinical application of berberine hydrochloride, and has significant economic and social benefits.