80 results about "Blood Circulation Time" patented technology

The invention relates to portable albumin binders, which are useful for improving the pharmacokinetic properties of diagnostic or therapeutic agents, in particular increasing the blood circulations time and / or the tissue penetration capacity of such agents.

In part, the present invention is directed to compositions and methods of making compositions comprising a polymeric backbone, a chelating group, a metal ion, and an active agent with a metal binding domain. The compositions can optionally further comprise protective groups. In part, the present invention is directed to prolonging the blood circulation time of an active agent containing a metal binding domain by using a composition comprising a polymeric backbone with a protective group, a chelator, and a metal ion.

The invention belongs to the technical field of medical diagnostic medicine and relates to a target tracing multi-mode diagnostic nano imaging medicine. The invention uses G5 as probe carrier to optimize blood circulation time and passive targeting of the target imaging medicine, marks near-infrared fluorescent group and Gd-DOTA paramagnetic group on G5 dendritic macromolecule, and links angiopep-2 polypeptide and G5 dendritic macromolecule by dual-functional polyethylene glycol PEG to make the nano imaging medicine with blood brain barrier overcoming ability and marked with optical and magnetic dual-functional imaging groups. PEG chain in the invention not only improves water solubility of nano probe and its blood circulation time, but also reduces the influence of steric hindrance of the dendritic macromolecule to the blood brain barrier overcoming ability of the angiopep-2 peptide chain. The medicine of the invention can be used to noninvasive dynamic tracing of in-situ cerebral gliomas and can have excellent target tracing function to neuroglioma when the blood brain barrier is not destroyed.

The invention relates to portable albumin binders, which are useful for improving the pharmacokinetic properties of diagnostic or therapeutic agents, in particular increasing the blood circulations time and / or the tissue penetration capacity of such agents.

Nanoparticles containing nucleic acid and suitable for use as in vivo delivery agents for nucleic acids are provided. The nanoparticles use a covalent conjugate of a polycation such as polyethylenimine and phospholipids. The final DNA- containing nanoparticle has a vesicular structure with a polyplex core surrounded by a mixed lipid / PEG- lipid monolayer envelope and offers simple preparation, high loading capacity, and in vivo stability. The nanoparticles have good in vivo stability and a prolonged blood circulation time and can effectively deliver a gene to a biological target such as a tumor.

The invention relates to a preparation method of hollow mesoporous silica loaded by nanometer star-shaped gold particles. The method includes the steps of forming solid silicon wrapped by meso-porous silicon in an ethyl alcohol, ultrapure water and ammonia mixed solution with ethyl orthosilicate as a silicon source, etching the solid silicon through sodium carbonate to form hollow mesoporous silica, modifying the surface of the hollow mesoporous silica by sulfydryl and loading the surface of the hollow mesoporous silica with nanometer gold particles so that the hollow mesoporous silica can serve as seeds, making the seeds grow into the hollow mesoporous silica loaded by nanometer star-shaped gold particles in a chloroauric acid solution, and wrapping perfluorohexane and modifying polyethylene glycol with one end being -SH. The prepared nanometer particles have excellent biocompatibility and long in-vivo blood circulation time, have good US / CT / PA imaging and photo-thermal treatment effects and are wide in application prospects, and a new method is provided for development of multi-mode imaging contrast media and treatment integrated platforms.

The invention belongs to the field of pharmaceutical preparations, and relates to preparation of a novel target nano carrier and application of the novel target nano carrier in a camptothecin drug targeting delivery system. The system can be represented as PAMAM-HA / drug, wherein PAMAM is polyamide amine-amine arboraceous macromolecules of different generations, HA is hyaluronic acid of different molecular weights, and the drug is one or more of camptothecin anticancer drugs such as camptothecin, 10- hydroxycamptothecine, topotecan and the like. The carrier is used for wrapping the camptothecin drugs, and has the actions of prolonging the drug blood circulation time, improving the drug bioavailability, reducing the non-tumor part concentration of the drug, reducing the drug cytotoxicity, and simultaneously protecting the lactonic rings of the camptothecin drugs from damage, thereby improving the tumor treatment efficiency from multiple aspects. The nano carrier provided by the invention has important significance in promoting the safe delivery of the camptothecin drugs and the effective treatment of tumor.

The present invention relates to a quercetin long-acting liposome powder injection and its preparation method. Said powder injection is formed from quercetin, polyethylene glycol-ethanolamine phosphoglycerides, lecithin, cholesterol and excipient. Said invention also provides the concrete steps of its preparation method.

The invention relates to multifunctional gold and silver core-shell nanoparticles. The gold nanopartciles are covered by silver nano shell layers and the nanoparticles with silver core shell structures are conducted for surface modification through sulfydryl polyethylene glycol molecules; and gold nano core particles are 3 to 20 nm in size, and silver nano shells are 2 to 12 nm in size. Especially, the gold and silver core-shell nanoparticles covered by the silver nano core and shells are prepared by reducing chloroauric acid to prepare ultrafine fold nanopartciles through tetrakisphosphonium chloride activated by alkaline liquor as a reducing agent, and reducing a silver nitrate solution by nanoparticles as crystal nucleuses; and a CT (Computed Tomography) contrast medium with long-efficiency blood circulation time and an anti-infective function is obtained by performing surface modification for the gold and silver core-shell nanoparticles through polyethylene glycol modified by tail sulfhydrylation. The multifunctional gold and silver core-shell nanoparticles are uniform in particle size, good in water solubility, and free from obvious agglomeration, and the core-shell nanoparticles have stronger dissipation capacities on X rays, thereby being superior to effective developing time of CT of traditional contrast medium ioversol; and the core-shell nanoparticles effectively inhibit infection of bacteria through a contrast medium injection window.

The invention discloses antitumor platinum drug mineralization protein nanoparticles and a preparation method and application thereof. The antitumor platinum drug mineralization protein nanoparticlesand the preparation method thereof have the advantages that the platinum drug mineralization protein nanoparticles are successfully prepared through the two-step preparation method for the first time,the prepared nanoparticles can be uniformly dispersed in an aqueous solution, the nanoparticles has good cytotoxicity, and the IC50 of the nanoparticles to human non-small-cell lung cancer cells A549is 6.9 microgram / ml; the platinum drug mineralization protein nanoparticles comprising a platinum drug and protein are simple in preparation process, uniform in size, controllable in particle size, good in biocompatibility, good in water solubility, long in blood circulation time, high in tumor targeting performance and capable of laying a foundation for efficient tumor treatment or drug-resistant tumor treatment.

The invention provides a bionic nanocarrier for treating GBM (glioblastoma) and a preparation method of the bionic nanocarrier and belongs to the field of biomedical engineering. According to the bionic nanocarrier for treating the GBM and the preparation method of the bionic nanocarrier, Ang-RBCm-CA / siRNA comprises Ang-RBCm (Ang (Angiopep-2) polypeptide modified red blood cell membrane) and citraconic anhydride grafted polylysine and polyethylenimine-siRNA compound (CA / siRNA). Ang-RBCm-CA / siRNA can effectively carry siRNA and protect siRNA against degradation. The Ang-RBCm-CA / siRNA has prolonged blood circulation time and high blood brain barrier penetrability, can be efficiently taken in by U87MG brain glial cells over-expressed by a low-density LPR (lipoprotein receptor) and can realizerapid charge conversion in endosome / lysosome, effectively release siRNA and effectively treat in-situ U87MG GBM.

Nanoparticles containing nucleic acid and suitable for use as in vivo delivery agents for nucleic acids are provided. The nanoparticles use a covalent conjugate of a polycation such as polyethylenimine and phospholipids. The final DNA-containing nanoparticle has a vesicular structure with a polyplex core surrounded by a mixed lipid / PEG-lipid monolayer envelope and offers simple preparation, high loading capacity, and in vivo stability. The nanoparticles have good in vivo stability and a prolonged blood circulation time and can effectively deliver a gene to a biological target such as a tumor.

The invention discloses a tri-block polymer and a preparation method thereof. The tri-block polymer takes fatty acid as a core, takes poly-L-lysine as a middle layer and takes N-succinyl chitosan as a casing to be self-assembled into a micelle in an aqueous solution. The hydrophobic core is used for entrapping hydrophobic anti-cancer drugs, such as Adriamycin, Taxol and the like; the middle layer carrying positive charges is used for adsorbing genes, such as DNA, siRNA and the like, and the prepared micelle can release the supported genes after being degraded; the hydrophilic casing can reduce the toxicity of the poly-L-lysine and prolong the blood circulation time of the poly-L-lysine after system administration. According to the tri-block polymer, the genes are adsorbed after particles are formed, so that the control on sizes of the micelle particles and large-scale preparation of the micelle particles are facilitated; the tri-block polymer can also being used for transfecting the genes to enter target cells and regulate expression of interest protein in the presence of serum and has the good biocompatibility, and a novel supporter and a novel preparation form are provided for the establishment of a targeted anti-tumor drug delivery system.

The invention discloses a sulforaphane preparation. The sulforaphane preparation comprises sulforaphane, mesoporous silica and a lipid membrane. The surface of the mesoporous silica is provided with nanoscale apertures. The nanoscale apertures are filled with sulforaphane. The surfaces of the mesoporous silica nano-particles carrying sulforaphane are coated with the lipid membrane. The invention also discloses a preparation method and a use of the sulforaphane preparation. The sulforaphane preparation has positive effects of cancer treatment, can substantially improve sulforaphane stability, has slow release and targeting dual-effects, can keep long blood circulation time and necessary plasma concentration, can recognize cancer tissue or cells, can realize intracellular administration by cell endocytosis and has a very wide application prospect.

The invention relates to a preparation method of SPECT / CT (Single Photon Emission Computed Tomography / Computed Tomography) dual-mode imaging contrast agent based on a second-generation polyamide-amine dendritic polymer. The method comprises the following steps: by taking the second-generation polyamide-amine dendritic polymer as a template material, sequentially modifying a radionuclide 99mTc chelating agent NOTA and a pegylated RGD (Arginine-Glycin-Aspartate) molecule on the surface; coating gold nanoparticles through an in-situ reduction synthesis method; and finally, labeling the radionuclide 99mTc, thereby obtaining the product. The SPECT / CT contrast agent prepared by the method disclosed by the invention has excellent colloidal stability, excellent biocompatibility, long blood circulation time and excellent in-vitro / vitro SPECT / CT imaging effect, has a specific targeting effect on C6 cells of an alphavbeta3 integrin receptor on the cell membrane surface and provides a good thought for developing a novel dual-mode nano contrast agent.

The invention relates to a preparation method of a CT nano contrast agent namely low-algebraic tree-shaped macromolecule-coated gold nano particles with a liver cancer targeting function. The preparation method comprises the following steps: dissolving LA-PEG-COOH into a solvent, adding EDC to activate the LA-PEG-COOH for 4 to 6 hours, dropwise adding the solution into a G2-FITC solution, stirring to carry out reactions, performing dialysis, and freeze-drying so as to obtain G2-FITC-PEG-LA; dissolving G2-FITC-PEG-LA into distilled water, adding a chloroauric acid water solution, stirring for 10 to 20 minutes, then adding a NaBH4 water solution, stirring to carry out reactions for 2 to 3 hours, performing dialysis, and freeze-drying so as to obtain the target product. The raw materials are cheap, and the gold nano particles which are prepared by taking a low-algebraic tree-shaped macromolecule as the template, has excellent stability and bio-compatibility. The in-vivo blood circulation time of the gold nano particles is prolonged, and moreover the gold nano particles have a specific targeting function on liver cancer cells, so the gold nano particles are advantageously used in the early-stage tumor detection.

The invention belongs to the technical field of nano biomedical imaging, and relates to a small-size (8-50 nm) near-infrared II fluorescence imaging contrast agent, a preparation method and application thereof. The small-size contrast agent is formed by self-assembling a four-arm star-shaped molecular brush polymer in a water solution, wherein the star-shaped molecular brush polymer takes a conjugated infrared II fluorescent dye as a core, has four hydrophilic side chains of polymethacrylate oligo-polyethylene glycol ester, and can be assembled into a small-size near-infrared II fluorescence imaging contrast agent with the particle size of 8-50 nm in an aqueous solution. Compared with the existing near-infrared II fluorescence imaging contrast agent, the small-size near-infrared II fluorescence imaging contrast agent prepared by the preparation method disclosed by the invention has the advantages of excellent water solubility, small molecular size, long in-vivo blood circulation time, high tumor accumulation and good fluorescence imaging effect in a near-infrared II.

The invention provides a self-microemulsion composition which comprises one kind or multiple kinds of materials in oleanolic acid, water-insoluble oleanolic acid and difficultly water-soluble oleanolic acid derivant. The self-microemulsion composition also comprises an oil phase, a surface active agent and a cosurfactant, and the self-microemulsion composition does not contain water. The invention overcomes the defect that the solubility of the oleanolic acid in water is very low, provides the self-microemulsion composition capable of being diluted into the microemulsion with the nanometer level grain diameters by water or water solution, and also provides the microemulsion which obviously improves the dispersivity and the solubility of the oleanolic acid, the water-insoluble oleanolic acid and the difficultly water-soluble oleanolic acid derivant in water, so the bioavailability is improved, the half-life and the blood circulation time of the oleanolic acid can be prolonged, in addition, the microemulsion can be targeted to the tumor because of the nanometer grain diameter of the microemulsion, the curative effect of the medicine can be improved, the medicine toxin can be reduced, and in addition, filtration and sterilization can be realized, and the needle applicability of the injection can be improved. The invention also provides preparation methods of the self-microemulsion composition and the microemulsion.

The invention discloses a tri-block polymer micelle, a preparation method and an application. The tri-block polymer micelle is formed by self-assembly of a tri-block polymer, takes fatty acid as a core, takes poly-L-lysine as a middle layer and takes N-succinyl chitosan as a casing to be self-assembled into the micelle; the hydrophobic core is used for entrapping hydrophobic anti-cancer drugs, the middle layer carrying positive charges is used for adsorbing genes, the micelle can release the supported genes after being degraded, and the hydrophilic casing is used for reducing the toxicity of the poly-L-lysine and prolonging the blood circulation time of the poly-L-lysine after system administration. According to the micelle, the genes are adsorbed after particles are formed, so that the control on sizes of the micelle particles and large-scale preparation of the micelle particles are facilitated; the delivery system can transfect the genes to enter target cells and regulate expression of interest protein in the presence of serum and has the good biocompatibility. The micelle can support the hydrophobic anti-cancer drugs and genes simultaneously and play a synergistic anti-tumor role.

The invention provides a polyethylene glycol modified metal organic nano material. The polyethylene glycol modified metal organic nano material is prepared from a metal organic nano material and poly-L-histidine-polyethylene glycol modified on the metal organic nano material. The polyethylene glycol modified metal organic nano material is particularly a poly-L-histidine-polyethylene glycol modified metal organic skeleton nano material and has good dispersibility, long blood circulation time and high tumor enrichment efficiency and very good water solubility and biocompatibility; the polyethylene glycol modified metal organic nano material can serve as a pure medicine carrier-free system and is applied to oncotherapy and particularly treatment of living body level, by means of tail intravenous injection, high enrichment can be achieved on the part of a tumor, and compared with the situation of directly using cisplatin, the antitumor activity is obviously improved; meanwhile, the toxic and side effects are effectively reduced, and damage cannot be caused to other parts.

Polyglutamates are well known to be highly biocompatible, biodegradable and multifunctional polymers, which have been already used as building blocks in polymer drug conjugates and polymeric micelles. Those systems have been applied to various medical applications ranging from therapy to molecular imaging. Furthermore a polyglutamic acid (PGA) paclitaxel conjugate has already entered clinical studies (Opaxio™ PGA-PTX conjugate currently in phase III of Clinical trials).In this context, a synthetic pathway to a plethora functional polyglutamates (homopolymers, block-co-polymers, triblocks) with well-defined structure, adjustable molecular weight (Mw) and low dispersity (D=Mw / Mn<1.2) applying the ring opening polymerization (ROP) of N-carboxyanhydrides (NCA) has been developed. Additionally, the acid moieties of the polyglutamates can be activated with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium (DMTMM) and various functionalities can be easily introduced by “post-polymerization modification” yielding a set orthogonal reactive attachment sides. The reactive moieties, such as azides, maleimides, thiols, alkynes (linear or cyclic) offer the opportunity of specific conjugation of the drugs, targeting moieties or markers. Besides introducing reactive groups the functionalization strategy was also used for PEGylation of PGA reducing charge induced interactions and therefore pharmacological properties, such as blood circulation time may be adjusted.In summary, a tool kit of various polyglutamates has been developed enabling the synthesis of a variety of polymer drug conjugates or polymer based imaging agents. The functional polymeric precursors developed will allow us to functionalize and therefore adjust the polymer properties to a desired application.

The invention provides a polymer shown as formula (I) in the description and a preparation method of the polymer. The prepared polymer has narrower polydispersity index. The invention further discloses a polymer-antitumor drug conjugate and a preparation method thereof. The prepared polymer-antitumor drug conjugate has longer blood circulation time and can obtain more drug accumulation at a tumorpart, so that a drug has better antitumor effect and has broad market application prospects.

Polyglutamates are well known to be highly biocompatible, biodegradable and multifunctional polymers, which have been already used as building blocks in polymer drug conjugates and polymeric micelles. Those systems have been applied to various medical applications ranging from therapy to molecular imaging. Furthermore a polyglutamic acid (PGA) paclitaxel conjugate has already entered clinical studies (Opaxio™ PGA-PTX conjugate currently in phase III of Clinical trials).In this context, a synthetic pathway to a plethora functional polyglutamates (homopolymers, block-co-polymers, tribocks) with well-defined structure, adjustable molecular weight (Mw) and low dispersity (D=Mw / Mn<1.2) applying the ring opening polymerization (ROP) of N-carboxyanhydrides (NCA) has been developed. Additionally, the acid moieties of the polyglutamates can be activated with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium (DMTMM) and various functionalities can be easily introduced by “post-polymerization modification” yielding a set orthogonal reactive attachment sides. The reactive moieties, such as azides, maleimides, thiols, akynes (linear or cyclic) offer the opportunity of specific conjugation of the drugs, targeting moieties or markers. Besides introducing reactive groups the functionalization strategy was also used for PEGylation of PGA reducing charge induced interactions and therefore pharmacological properties, such as blood circulation time may be adjusted.In summary, a tool kit of various polyglutamates has been developed enabling the synthesis of a variety of polymer drug conjugates or polymer based imaging agents. The functional polymeric precursors developed will allow us to functionalize and therefore adjust the polymer properties to a desired application.

The invention discloses applications of a compound containing an N-oxidized tertiary amine group as a cell mitochondria targeting carrier, wherein the compound contains one or a plurality of N-oxidized tertiary amine structure units, the N-oxidized tertiary amine structure unit at least comprises one selected from the following groups represented by formulas (I), (II) and (III), R1 and R2 are respectively and independently alkyl, substituted alkyl, aryl, substituted aryl or a polymer main chain, and R3 and R4 are respectively and independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl or a polymer main chain. According to the present invention, the compounds are electrically neutral, have the similar water solubility, the similar biocompatibility and the similar long bloodcirculation time to polyvinyl alcohol (PEG), and can rapidly enter cells and be highly-selectively enriched in cell mitochondria; and the drug modified with the compound containing the N-oxidized tertiary amine group or the probe can specifically treat or label mitochondria.

The invention relates to a preparation method of a G2.NH2 based manganese-based MR / CT (Magnetic Resonance / Computerized Tomography) dual-mode imaging contrast agent with an RGD (arginine-glycine-aspartic acid) targeting function. The preparation method comprises the following steps: mixing G2.NH2 and NOTA and reacting to obtain G2-NOTA; then mixing COOH-PEG-MAL and RGD and reacting to obtain COOH-PEG-RGD; after carrying out activation treatment, reacting with the G2-NOTA to obtain G2-NOTA-PEG-RGD; reacting with a chloroauric acid solution and a pre-cooled sodium borohydride solution to obtain G2-NOTA-PEG-RGD@Au; mixing G2-NOTA-PEG-RGD@Au with MnSO4 and reacting to obtain a product. The MR / CT contrast agent prepared by the preparation method has good colloid stability, excellent biocompatibility, relatively long blood circulation time and relatively high relaxation rate; the MR / CT contrast agent has a specific targeting effect on in-situ brain glioma of a mouse and a good thought is provided for developing a novel dual-mode nano contrast agent.

The invention discloses targeted folic acid-polyethylene glycol-lignin conjugate medicine-carrying nano particles and a preparation method thereof. The particles are characterized in that a folic acid-polyethylene glycol-lignin conjugate is formed by chemically connecting folic acid, amidogen-polyethylene glycol-carboxyl and lignin, lignin is used as a framework material, amidogen-polyethylene glycol-carboxyl is used as a connection arm, folic acid is used as a targeted molecule, and the folic acid-polyethylene glycol-lignin conjugate is self-assembled in an aqueous solution and wraps 10-hydroxycamptothecin to form the targeted medicine-carrying nano particles. According to the medicine-carrying nano particles, the solubility, the stability, the permeability and the targeting performance of medicine can be effectively improved, the blood circulation time of the medicine can be effectively prolonged, and the particles have wide application prospects.

The invention relates to a hyperstable monodisperse fluorescent magnetic diagnosis and treatment nanoprobe and a preparation method and application thereof. The nanoprobe comprises magnetic nano particles coating polyethylene glycol PEG and a CaCO3 coating layer doped with a photosensitizer, wherein a mass ratio of the magnetic nano particles to the CaCO3 coating layer is 10 to (1 to 3), and the load of the photosensitizer is 8.9-10.3 wt%; ascorbic acid is placed in an iron salt solution, a solution pH is adjusted to be 9 to 12, and through hydrothermal reaction, magnetic nano particle dispersion liquid is obtained; CaCl2 and ICG are added into the magnetic nano particle dispersion liquid, reaction is carried out while stirring, and then Na2CO3 and ICG are added for reaction for 24 hours to obtain a target product. The nanoprobe is used for bimodal imaging in an animal body, and has the advantages that blood circulation time is long, tumor location retention time is long, the medicinetargeted delivery efficiency is high, a preparation technology is simple, and the like.

The invention discloses a gadolinium coordination polymer network microsphere and application thereof to magnetic resonance imaging and belongs to the field of material science and biomedical application. The coordination polymer network microsphere is of a net-shaped crosslinking structure; specifically, after an acrylic monomer is coordinated with gadolinium ions, the net-shaped cross-linked gadolinium coordination polymer network microsphere is formed through coordination and free radical polymerization. A preparation method of the polymer microsphere is simple and the cost is low; the polymer microsphere has a stable structure and has a relatively high relaxation rate, a relatively good T1 imaging effect and long blood circulation time; the polymer microsphere has extremely great potential application value in the aspects of diagnosis and treatment of cancers and tumors.

The invention discloses a preparation method of a MnO2 carrier coated pharmaceutical precursor 5- ALA. The method comprises the following steps: first, dissolving 100 mg of 5-ALA in 2ml of deionized water to adjust the pH to 7 for storage; then putting 250mu L of 50 mg / ml 5-ALA, 14mg of EDC, 9.3mg of NHS and 4.8ml deionized water into a 25ml round-bottom flask, and reacting at room temperature for30min; then adding 0.486g of BSA, and reacting at room temperature for 12h; dissolving 14mg of MnCl2 and 4H2O in 1ml water, dropwise adding the obtained solution to the reaction solution obtained inthe above step, and adjusting the pH of the reaction solution to 11 with 1M NaOH; then transferring the reaction solution to a dialysis bag after 2h, dialyzing for 3 days in deionized water to obtaina final product, and storing the final product in a refrigerator at 4 DEG C. By using synthetic protein and drug molecular complex, and mineralizing multi-response type MnO2, the MnO2 carrier coated drug precursor not only can be used as a stabilizer to mineralize and synthesize MnO2, but also can be used as a carrier of 5-ALA to enhance the blood circulation time, thereby realizing enhanced photodynamic therapy.