8498results about "Nanocapsules" patented technology

The invention relates to a dialkyl imidazole bionic lipid compound and a preparation method and application thereof.The structure of the dialkyl imidazole bionic lipid compound imitates natural phospholipid design, alkyl with no less than 10 carbon atoms is modified on the fourth site and the fifth site of imidazole, and primary amines with different alkyl chain lengths are modified on the second site; the dialkyl imidazole bionic lipid compound is mixed with a therapeutic drug and other auxiliary materials to prepare lipid nanoparticles loaded with the therapeutic drug, and the lipid nanoparticles can be used as a drug delivery system for preparation of brain-targeted drugs. The dialkyl imidazole bionic lipid has the function of dynamically regulating and controlling the blood-brain barrier, and can realize reversible opening of the blood-brain barrier; the formed drug-loaded lipid composition can pass through a blood brain barrier and well realize brain-targeted delivery of loaded therapeutic drugs; the drug-loaded lipid composition composed of the dialkyl imidazole bionic lipid belongs to a new generation of bionic nano-drug carriers, and provides a new strategy for realizing brain-targeted delivery of different types of drugs.

The invention discloses injectable sodium hyaluronate-silk fibroin composite hydrogel and a preparation method and application thereof.The injectable sodium hyaluronate-silk fibroin composite hydrogel is composed of sodium hyaluronate composite gel particles and a sodium hyaluronate solution, and the sodium hyaluronate composite gel particles comprise silk fibroin sponge microspheres and sodium hyaluronate gel particles; the silk fibroin sponge microspheres are loaded on the sodium hyaluronate gel particles, the silk fibroin sponge microspheres are physical crosslinking microspheres, the particle size D50 is 10-30 [mu] m, and the particle size D90 is within 100 [mu] m; the sodium hyaluronate gel particles are chemical cross-linked particles, the particle size D50 is 150-300 microns, and the particle size D90 is within 800 microns. After the sodium hyaluronate gel particles are in contact with tissues, sodium hyaluronate is preferentially degraded, and silk fibroin exposed in the degradation process has better degradation resistance and an effect of stimulating generation of collagen fibers, so that in-situ fixation of the composite gel particles is realized, and an instant and lasting filling effect is achieved; the material is a safe and effective medical beauty filling material.

The present disclosure provides compounds according to Formulae I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIII, and XIV for use as a component in a lipid nanoparticle composition for the delivery of biological and / or therapeutic agents. The present disclosure also provides novel, stable lipid nanoparticle compositions comprising one or more biological and / or therapeutic agents, as well as methods of making and delivering lipid nanoparticle compositions.

The present disclosure describes improved LNP-based RNA vaccines, nucleobase editing systems, and therapeutics for use in treating and / or immunization against disease. In particular, the disclosure describes improved LNPs, including novel and improved ionizable lipids for making LNPs, that enhance the targeted delivery of LNP-based RNA vaccines and therapeutics based on linear and / or circular mRNAs. The improved LNPs protect linear and / or circular mRNA payloads from degradation and clearance while achieving targeted systemic or local delivery for use as enhanced vaccines and / or therapeutic agents.

Systems for analyzing biological components are provided. The systems may include a fluidic device and an energy source in communication with the fluidic device. The energy source may supply energy to the fluidic device to form a polymer matrix on or adjacent to a biological component within the fluidic device. Methods of using the systems to analyze biological components are also provided.

Disclosed are compositions of lipid nanoparticles (LNP) comprising an ionizable cationic lipid, a phospholipid, a sterol, and a PEG-lipid (non-functionalized and optionally functionalized). The functionalized PEG-lipid can be conjugated with a binding moiety to create a targeted LNP (tLNP). The disclosed tLNP preferentially deliver a nucleic acid molecule or other negatively charged payload to cells expressing a cell surface antigen recognized by the binding moiety of the tLNP, and are better tolerated, as compared to LNPs and tLNPs comprising ionizable cationic lipids found in marketed pharmaceuticals comprising LNPs.

The invention provides an UTR (Untranslated Region) element H2202 P1-G as well as a construction method and application thereof, and relates to the technical field of mRNA (messenger ribonucleic acid). According to the present invention, the ribosome load prediction and the secondary structure optimization are performed on the natural 5 'UTR of the HIV TAT 202 gene through the BaidleHelix platform, and the obtained HTAT 202 P1 sequence avoids the inhibitory hairpin structure so as to significantly improve the luciferase expression quantity compared to the natural UTR; an ncRNA sequence without a secondary structure is introduced on the basis of the HTAT 202 P1, translation inhibition of a 5 'cap region is further relieved, and the protein expression quantity of the constructed H2202 P1-G mutant (the DNA sequence of the H2202 P1-G is as shown in SEQ NO 1, and the RNA sequence is as shown in SEQ NO 2) is further improved.

The invention belongs to the field of medicines, particularly relates to the technical field of targeted delivery lipids, and particularly discloses an ionizable cationic lipid targeting immune cells, a composition containing the ionizable cationic lipid and application of the ionizable cationic lipid. The immune cell targeting cationic lipid provided by the invention has a structure as shown in formula (I), can be used for RNA targeting delivery, and can significantly enhance the targeting effect of mRNA drugs on immune cells. # imgabs0 #

Compounds are provided having the following structure:or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein a, b, c, d, G1, G2, L1, L2, R1a, R1b, R2a, R2b, R3a, R3b, R4a, R4b, R5, R6, R7, R8 and X are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, nanoparticles comprising the compounds and methods for their use and preparation are also provided.

The present disclosure describes improved LNP-based RNA vaccines, nucleobase editing systems, and therapeutics for use in treating and / or immunization against disease. In particular, the disclosure describes improved LNPs, including novel and improved ionizable lipids for making LNPs, that enhance the targeted delivery of LNP-based RNA vaccines and therapeutics based on linear and / or circular mRNAs. The improved LNPs protect linear and / or circular mRNA payloads from degradation and clearance while achieving targeted systemic or local delivery for use as enhanced vaccines and / or therapeutic agents.

The invention provides an UTR element NHP1 as well as a construction method and application thereof, and relates to the technical field of mRNA. A 5 'UTR with a good expression effect is designed by integrating dominant sequences of a human high-expression gene and a pathogen natural UTR, a chimeric structure NHP1 with high ribosome load is predicted through a calculation model, a DNA sequence of the NHP1 is as shown in SEQ NO 1, and an RNA sequence of the NHP1 is as shown in SEQ NO 2; an EGFP report system is adopted on the DNA level to rapidly screen UTR; the translation efficiency is quantitatively evaluated on the RNA level through luciferase mRNA (N1-methyl pseudouridine modification); and the particle size is controlled by a microfluidic technology, so that the optimized UTR-mRNA is efficiently expressed after being delivered.

The present disclosure provides lipid nanoparticle compositions comprising a nucleic acid encoding a therapeutic polypeptide. The disclosure also provides novel IL-15 polypeptides, fusion proteins comprising the IL-15 polypeptides, and nucleic acids encoding the IL-15 polypeptides and the fusion proteins.

The present invention discloses a pharmaceutical composition comprising a circular RNA and a drug delivery carrier. Compared with traditional linear 1 * siRNA and annular 1 * siRNA, the number of repeated series connection of positive-sense strands is increased to include but not limited to two or more, it is accidentally found that the silence effect is remarkably enhanced, the expression level of the PCSK9 gene can be remarkably reduced, and degradation of mRNA of PCSK9 protein is mediated. The nano-particles are used for delivering oligonucleotide, so that the stability is improved, the immunogenicity is reduced, the effects of lowering cholesterol, reducing aortic plaque load and resisting atherosclerosis are improved, and the nano-particles are safe and free of obvious liver and kidney toxicity and have a wide application prospect in the aspect of preparing medicines for treating hypercholesterolemia and coronary heart disease.

The invention discloses a probiotic-polyphenol nanoparticle colon-targeted co-delivery system as well as a preparation method and application thereof, and belongs to the field of biological medicines. The FCPs and hyaluronic acid (HA) are combined through non-covalent interaction, so that the hydrogel has colon targeting property and mucosal adhesion at the same time, and delivery of probiotics is facilitated. The hydrogel (HF) based on polysaccharide has good biocompatibility, and can be used for effectively encapsulating the probiotics and the natural products. Then, the PDA-TH NPs and BA are incorporated into the polysaccharide chain network of HF, and finally the BA-HF-PDAT targeted co-delivery system is constructed. The BA (at) HF-PDAT targeted co-delivery system can protect BA from serious gastrointestinal stress, and is jointly assembled with PDT-TH NPs to realize dual slow release of thymol (Thy), so that the treatment effect of BA and Thy is improved, and the BA (at) HF-PDAT targeted co-delivery system contributes to treatment of clostridium difficile infection (CDI).

The present application relates to a kind of dihydrocarbylimidazole biomimetic lipid compound and its preparation method and application, dihydrocarbylimidazole biomimetic lipid compound structure imitates natural phospholipid design, modification is not less than 10 carbon atoms alkyl on the 4th and 5th of imidazole, and modification is different alkyl chain length primary amine on 2nd position;Dihydrocarbylimidazole biomimetic lipid compound is mixed with therapeutic drug and other adjuvant, can be prepared to be loaded in the lipid nanoparticle of therapeutic drug, can be used as drug delivery system for the preparation of brain-targeted drug.Dihydrocarbylimidazole biomimetic lipid has the function of dynamic control blood-brain barrier, can realize the reversible opening of blood-brain barrier;Formed drug-loaded lipid composition can cross blood-brain barrier and better realize the brain-targeted delivery of loaded therapeutic drug;Drug-loaded lipid composition consisting of dihydrocarbylimidazole biomimetic lipid belongs to a new generation of biomimetic nanomedicine carrier, provides new strategy for realizing the brain-targeted delivery of different kinds of drugs.

The invention provides an antibacterial synergy-mineralization regulation difunctional nano material as well as a preparation method and application thereof, and belongs to the technical field of biomedical materials. The preparation method comprises the following steps: mixing a disodium hydrogen phosphate solution and a calcium chloride solution to obtain an amorphous calcium phosphate suspension; mixing the amorphous calcium phosphate suspension with a tannic acid solution to obtain an ACP-TA suspension; and finally, mixing the ACP (at) TA suspension and the hydroxypropyl trimethyl ammonium chloride chitosan solution to obtain the bifunctional nano material. A cross-linked shell is formed through the electrostatic adsorption effect of tannic acid and hydroxypropyl trimethyl ammonium chloride chitosan of the antibacterial layer, amorphous calcium phosphate is effectively wrapped, the crystallization process of amorphous calcium phosphate can be remarkably delayed, long-acting release of calcium and phosphorus ions is ensured, the antibacterial function can be effectively achieved, and the service life of the coating is prolonged. An ideal local microenvironment is provided for remineralization of tooth hard tissue, and finally biomimetic mineralization of enamel and deep mineralization plugging of dentinal tubules are achieved.

The invention provides an immunologic adjuvant composition as well as a preparation method and application thereof. The immunologic adjuvant composition comprises an immunologic active agent and a liposome for loading the immunologic active agent, wherein the immunologic active agent comprises saponin and CpG oligodeoxynucleotide. The immunologic adjuvant composition can induce immune response of mammals to human herpes virus and / or hepatitis B virus, and can induce generation of a relatively high cellular immune response level. The QS21 and the CpG oligodeoxynucleotide are simultaneously loaded by using the liposome, so that the QS21 and the CpG oligodeoxynucleotide have a better synergistic effect in the aspect of promoting cellular immunity, and compared with a Shingrix commercially available vaccine, the vaccine can induce generation of a higher cellular immune response level.

The invention relates to application of a targeted inhibition circPDK1 reagent in preparation of an anti-esophageal cancer drug, and belongs to the field of biological medicines. The reagent for targeted inhibition of circPDK1 expression provided by the invention is shRNA or siRNA, and in-vivo and in-vitro experiments prove that the reagent can significantly inhibit circPDK1 expression and inhibit growth and migration of esophageal cancer tumor cells; after siRNA of targeted annular circPDK1 is packaged into efficient and low-toxicity LNP-siRNA, circPDK1 expression is specifically silenced, proliferation and migration of esophageal cancer tumors can be remarkably inhibited, and a basis is provided for clinical treatment and scientific research of esophageal cancer related circRNA.

The invention relates to the technical field of biological medicine, and discloses a pharmaceutical composition of paclitaxel dimer prodrug nanoparticles and a traditional Chinese medicine compound and application of the pharmaceutical composition, and the pharmaceutical composition is composed of Qiyuansanlong prescription freeze-dried powder and paclitaxel dimer prodrug nanoparticles; wherein the paclitaxel dimer prodrug nanoparticles comprise one of NQO1 response type PTX dimer prodrug nanoparticles (PTX-Q-PTX NPs) or GSH (glutathione) response type PTX dimer prodrug nanoparticles (PTX-SeSe-PTXNPs), and the paclitaxel dimer prodrug nanoparticles comprise one of NQO1 response type PTX dimer prodrug nanoparticles (PTX-Q-PTX NPs) and GSH response type PTX dimer prodrug nanoparticles (PTX-SeSe-PTXNPs). According to the pharmaceutical composition disclosed by the invention, a traditional Chinese and western medicine synergistic treatment system is innovatively constructed, and the advantage of multi-dimensional synergistic interaction is shown. Firstly, an NQO1 / GSH double-response type intelligent release system is adopted, and a biomarker highly expressed by tumor tissue can be specifically responded to realize precise drug release, so that the PTX concentration in tumors is improved compared with that of a traditional dosage form, and meanwhile, the drug circulation time is prolonged. Secondly, the active ingredients in the Qiyuansanlong prescription freeze-dried powder can significantly down-regulate the PD-L1 expression level, synergistically enhance CD4 + T and CD8 + T cell infiltration, and form chemical-immune dual killing effects.

The invention discloses a preparation method and application of plant-derived extruded nano-vesicles, and relates to the technical field of biological medicines. The preparation method of the plant-derived extruded nano-vesicles comprises the following steps: juicing cleaned plant roots, stems, leaves, flowers or fruits to obtain plant juice, and filtering with gauze to obtain first filtrate; centrifuging the first filtrate at a low speed of 300-6000 * g to obtain a second filtrate; performing 8,000-20,000 * g centrifugation on the second filtrate for 0.5-3 hours at the temperature of 0-5 DEG C, so as to obtain a first precipitate; adding the first precipitate into a buffer solution, carrying out ultrasonic treatment, diluting, and sequentially passing through a filter membrane with the pore diameter of 0.4-10 microns and a filter membrane with the pore diameter of 0.1-0.4 microns, so as to obtain a third filtrate; and centrifuging the third filtrate, taking the precipitate, and resuspending to obtain the extruded nano-vesicles. Experimental detection shows that the extruded vesicles are similar to natural vesicles in characteristics, but the yield is far higher than that of the natural vesicles, and the extruded vesicles can serve as nano-carriers to be applied to a foundation or clinic.

The present disclosure includes ionizable lipids suitable for lipid nanoparticle compositions and pharmaceutical formulations thereof. The lipids have general formula (I).

Water-soluble conjugates of verteporfin are provided, which find therapeutic use, including by topical administration. Also provided are liposomal verteporfin formulations, which may be admixed with biomolecules such as hyaluronic acid.

Compounds are provided having the following structure:or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein R1, R2, R3, R4, R5, L1, L2, L3, G1, G2, and G3 are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds and methods for their use and preparation are also provided.

Compounds are provided having the following Formula (I):or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein R1, R2, R3a, R3b, R3c, R3d, L1, L2, and n are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds and methods for their use and preparation are also provided.

The invention discloses application of 4, 5-dialkyl imidazole cationic lipid in a drug brain delivery carrier, and belongs to the field of drug delivery. The 4-site and the 5-site of imidazole are respectively modified with alkyl with not less than 10 carbon atoms to form the 4, 5-dialkyl imidazole cationic lipid. The 1, 4, 5-dialkyl imidazole cationic lipid is mixed with a therapeutic drug and other lipid auxiliary materials to prepare drug-loaded lipid nanoparticles loaded with the therapeutic drug, and the drug-loaded lipid nanoparticles can be used as a drug delivery system for brain delivery of the therapeutic drug. The 1, 4, 5-dialkyl imidazole cationic lipid has the function of dynamically regulating and controlling opening and closing of a blood brain barrier, and reversible opening of the blood brain barrier can be achieved; the formed drug carrier can pass through a blood brain barrier and well realize brain delivery of loaded therapeutic drugs, and a new strategy is provided for brain delivery of different types of drugs.

Compounds are provided having the following structure:or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R3, L1, L2, G1, G2 and G3 are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds and methods for their use and preparation are also provided.

Provided is a pharmaceutical composition, comprising a circular RNA and a drug delivery carrier. It is surprisingly found that compared with conventional linear 1 x siRNAs and circular 1 x siRNAs, increasing the number of tandem repeats in the sense strand to two or more significantly enhances the silencing effect, significantly reduces the expression level of the PCSK9 gene, and mediates the degradation of the PCSK9 protein mRNA. The use of nano-particles for delivering oligonucleotides features improved stability, reduced immunogenicity, improved cholesterol-lowering, aortic plaque load-reducing and anti-atherosclerotic effects, good safety, no significant liver and kidney toxicity, and therefore good prospects in preparing medicaments for treating hypercholesterolemia and a coronary heart disease.

This disclosure provides methods of increasing in vivo transfection efficiency and pharmacologic activity of T cells, by administering multiple small doses within a compact time period of T cell-targeted lipid nanoparticles encapsulating mRNA encoding an antigen receptor that recognizes an antigen of a cell against which immune activity is to be directed. Also provided are methods of depleting B cells, and methods of treating B cell-mediated diseases and disorders by depleting B cells and achieving immunological reset, entailing administration of immune cell-targeted lipid nanoparticles encapsulating mRNA encoding an antigen receptor recognizing a B cell marker as multiple small doses within a compact time period. The antigen receptor can be a T cell receptor or a chimeric antigen receptor.

The invention relates to mRNA comprising lipid nanoparticles and their medical uses. The lipid nanoparticles of the present invention comprise a cationic lipid according to formula (I), (II) or (III) and / or a PEG lipid according to formula (IV), as well as an mRNA compound comprising an mRNA sequence encoding an antigenic peptide or protein. The invention further relates to the use of said lipid nanoparticles as vaccines or medicaments, in particular with respect to influenza or rabies vaccination.