59 results about "Bio distribution" patented technology

Particles, including nanoparticles and microparticles, and pharmaceutical formulations thereof, comprising conjugates of an RNAi agent attached to a targeting moiety via a linker have been designed which can provide improved temporospatial delivery of the RNAi agent and / or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or infectious diseases.

6-[18F]Fluoro-2-alkoxynicotinoyl substituted Lys-C(O)-Glu derivatives were identified as efficient imaging probes for PSMA expressing tissues in comparison to other known PSMA specific ligands like [18F]DCFPyL, [68Ga]HBED-CC-PSMA, [18F]PSMA-1007 and [Al18F]HBED-CC-PSMA. Unexpectedly, the 6-[18F]fluoro-2-alkoxy and 6-[18F]fluoro-4-alkoxy substituted analogs showed significant differences in accumulation in PSMA expressing prostate tumor cells. Whereas the 2-alkoxy derivative showed cellular uptake values higher than [18F]DCFPyL, the cellular uptake of the corresponding 4-alkoxy substituted derivative was significantly lower. Furthermore, in vivo PET studies with 2-alkoxy-substituted probes demonstrated excellent visualization of PSMA positive ganglia with extremely high target to background ratio. In contrast, the 4-alkoxy substituted derivatives showed less favorable biodistribution with significantly lower uptake in PSMA positive tissues. Especially, the 18F-labeled 2-methoxy derivate ((2S)-2-({[(1S)-1-carboxy-5-[(6-[18F]fluoro-2-methoxypyridin-3-yl)formamido]pentyl]carbamoyl}-amino)pentanedioic acid) demonstrated exceptional clinical efficiency in detecting small PCa lesions, including those which could not be visualized with [68Ga]HBED-CC-PSMA representing currently the gold standard for the diagnosis of recurrent PCa. Furthermore, this probe is easily accessible on a preparative scale in commercially available automated synthesis modules like GE FASTlab and TRACERlab FX N Pro. Consequently, the novel probe is a valuable tool for the visualization of ganglia and reendothelialization as well as for the diagnosis of glioma, neuropathic pain and atherosclerotic plaques.

Conjugates of an active agent attached to a targeting moiety, such as an HSP90 binding moiety, via a linker, and particles comprising such conjugates have been designed. Such conjugates and particles can provide improved temporospatial delivery of the active agent, improved biodistribution and penetration in tumor, and / or decreased toxicity. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer.

The invention provides a precise block polymer nanoassembly and a preparation method thereof. According to the invention, a precise amphiphilic block polymer with a structure as shown in a formula I is adopted as a matrix; and a controllable nanoassembly, namely a spherical micelle and / or rod-like micelle structure can be formed by adjusting the length and sequence structure of a hydrophobic chain segment and utilizing of cooperation with other operations and condition control; and the obtained nanoassembly is low in dispersity, good in stability, good in uniformity and repeatability and single in molecular weight, so the biological distribution of the nanoparticles corresponding to the polymer in a living body can be conveniently quantified by using a mass spectrum. The preparation method provided by the invention is simple and easy to implement, and product repeatability is good.

Particles, including nanoparticles and microparticles, and pharmaceutical formulations thereof, comprising conjugates of an RNAi agent attached to a targeting moiety via a linker have been designed which can provide improved temporospatial delivery of the RNAi agent and / or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or infectious diseases.

Conjugates of an active agent such as a therapeutic, prophylactic, or diagnostic agent attached to an HSP90 targeting moiety via a linker have been designed. Nanoparticles and microparticles comprising such conjugates can provide improved temporospatial delivery of the active agent and / or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or other diseases.

The invention provides a natural reserve protection vacancy analysis method and system, and relates to the field of ecological protection, and the method comprises the steps: carrying out the unit-area incremental evaluation of a physical environment, a biological environment and an interference factor of a target region according to a natural reserve vector diagram in the target region under a large resolution, obtaining an analysis result of whether a protection vacancy area exists in the target area; before or during the process, acquiring spatial geographical environment data of a target area to construct a basic database; collecting data representing ecological system and natural resource distribution characteristics, data representing biological distribution characteristics and datarepresenting ecological system service characteristics, and constructing an index database; and processing the basic database and the index database to enable the basic database and the index databaseto perform calculation under high resolution so as to obtain a macroscopic evaluation result of the target area. The method can realize identification of the protected vacant area of the natural reserve, is beneficial to guidance of ecological restoration and is beneficial to ecological environment protection.

The present invention relates to methods for identifying improved stereodefined phosphorothioate oligonucleotide variants of antisense oligonucleotides utilising sub-libraries of partially stereodefined oligonucleotides. The methods allow for the efficient identification of stereodefined variants with improved properties, such as enhancedin vitro or in vivo activity, enhanced efficacy, enhanced specific activity, reduced toxicity, altered biodistribution, enhanced cellular or tissue uptake, and / or enhanced target specificity (reduced off-target effects). Disclosed is a multiple parallel library screening approach where multiple exclusive or over-lapping short sub-regions or motifs of stereodefined phosphorothioate linked nucleosides are optimised to identify enhanced sub-libraries, and stereodefined internucleoside linkage patterns from each of the selected (improved) sub-libraries are then combined to produce an enhanced stereodefined compound.

The invention discloses a reversible cross-linked biodegradable polymer vesicle with an asymmetric membrane structure, a preparation method thereof and an application in nucleic acid medicine. Synthesized triblock polymer PEG-P(TMC-DTC)-PEI, PEG-P(DLLA-DTC)-PEI self-assembled and self-crosslinked to obtain polymersomes with asymmetric membrane structure, or connected with Targeted RCCPs are self-assembled by targeting molecules, the inner shell is PEI for complexing and loading nucleic acids through electrostatic interaction; the membrane is reversibly cross-linked biodegradable and biocompatible polyester / polycarbonate, side chain The dithiolane is similar to the human body's natural antioxidant lipoic acid, and the outer shell is based on PEG, which can target cancer cells. To study carrier complex functional siRNA, its in vivo and in vitro gene silencing effects, in vivo blood circulation and biodistribution, treatment of mice bearing orthotopic lung cancer and toxic and side effects, it is expected to become a simple, stable, multifunctional nano System platform for efficient, active targeted delivery of siRNA to tumors in situ.