229 results about "Liver targeting" patented technology

A test indicator for quantifying remaining liver function is provided. A novel liver receptor imaging agent with liver targeting property is utilized to develop a method for quantifying remaining liver function to serve as test indicator for judging the liver failure outcome in clinic, particularly for judging the necessity of liver transplantation for patients with liver failure or liver disease. The radioactivity uptake of the test indicator was negatively correlated with the extent of liver reserve. The cutoff value of liver reserve for liver transplantation is also disclosed.

A composition and an associated method for hepatic targeted delivery of thyroid receptor beta1 (TRβ1) agonist to a liver of a subject. The composition includes hydrophobic nanoparticles, a liver targeting moiety exterior to each nanoparticle and covalently bonded to each nanoparticle, and at least one TRβ1 agonist encapsulated within each nanoparticle. The nanoparticles include chitosan hybrid nanoparticles, amine-modified PLGA nanoparticles, solid lipid nanoparticles, and combinations thereof. The liver targeting moiety includes Glycyrrhetinic acid (GA), Lactobionic acid (LA), or combinations thereof.

A test indicator for quantifying remaining liver function is provided. A novel liver receptor imaging agent with liver targeting property is utilized to develop a method for quantifying remaining liver function to serve as test indicator for judging the liver failure outcome in clinic, particularly for judging the necessity of liver transplantation for patients with liver failure or liver disease. The radioactivity uptake of the test indicator was negatively correlated with the extent of liver reserve. The cutoff value of liver reserve for liver transplantation is also disclosed.

This application discloses phosphoramidate and phosphonoamidate prodrugs of alcohol-based therapeutic agents, such as nucleosides, nucleotides, acyclonucleosides, C-nucleosides, and C-nucleotides, and use of these prodrugs for treatment of diseases or disorders, including infectious diseases and cancers. This application also discloses a general method for enhancing bioavailability and / or liver-targeting property of alcohol drugs through converting the alcohol drugs to phosphoramidate or phosphonoamidate prodrugs, and methods of preparation of these prodrugs.

The invention relates to a common carrier material based on graphene oxide for a targeting anticancer drug and a gene and application and application. Folic acid, lactobionic acid and other tumor cell targeting or liver targeting molecules and part of amino groups of soluble chitosan are connected by amide bonds to prepare a conjugate, the conjugate is then connected with graphene oxide, quaternization is performed by using an epoxy compound with a quaternary ammonium group, and gene molecules are loaded by the quaternizationquaternized part of the chitosan through electrostatic attraction; and then the anticancer drug is loaded by pi-pi conjugates, hydrogen bonds and hydrophobic effects in a non-covalent bond method. By adopting the targeting performance of targeting molecules and effects of graphene oxide of a particular size to enhance penetration and retention in tumor tissues and combining the performance of the graphene oxide for pH response control release of the loaded drug, the drug can be realized released in a tumor cell, an intelligent delivery system for the common carrier of the tumor targeting or liver targeting anticancer drug and the gene is synthesized from the perspective of synergetic medication, and a theoretical basis and a method basis are provided for combined therapy of tumor.

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.

The invention provides a prodrug of an antiviral drug for use in liver of cyclic phosphate of a general formula (I) and isomers, pharmaceutical salts, hydrates, solvates and pharmaceutical compositions of the same. The invention provides uses of the compounds singly or together with other antiviral drugs in the treatment of viruses, in particular of hepatitis B viruses (HBV), hepatitis C virus (HCV), HIV viruses and / or human cytomegaloviruses (HCMV).

This invention provides novel liver targeting agents and their synthetic methods. A liver targeting agent, with a lysine based nitrilo triacetic acid structure as backbone which acquires multivalency with saccharide groups, to bind with a galactosamine chain or lactose chain is disclosed. In particular, only one amino acid L-lysine is involved to provide trivalency. All carboxyl groups in Nε-benzyloxycarbonyl-Nα-dicarboxymethyl-L-lysine can be conjugated with three glycosides of ahGalNAc or ahLac in one step. This invention also provides a hexa-lactoside. In particular, the TFA-AHA-Asp was used to conjugate 2 moles of NTA(ahLac)3. This invention also provides a method for adding a spacer between NTA and DTPA. The extended hepatocyte-specific glyco-ligand has higher 111In-radiolabelling yield than those non-extended.

The invention relates to a tenofovir cyclic phosphonate compound having a structure represented by a formula I and a pharmaceutically acceptable salt thereof, and preparation methods and applications thereof, wherein the compound represented by the formula I is a tenofovir pro-drug having a liver targeting character and is used for treatment of hepatitis B and resistance of human immunodeficiency virus infection.

This application discloses phosphoramidate and phosphonoamidate prodrugs of alcohol-based therapeutic agents, such as nucleosides, nucleotides, acyclonucleosides, C- nucleosides, and C-nucleotides, and use of these prodrugs for treatment of diseases or disorders, including infectious diseases and cancers. This application also discloses a general method for enhancing bioavailability and / or liver-targeting property of alcohol drugs through converting the alcohol drugs to phosphoramidate or phosphonoamidate prodrugs, and methods of preparation of these prodrugs.

The preparation method includes the following steps: modifying hepatic target compound onto degradable polymer (chitosan, polylysine, glucosan, agar, polyglutamic acid-benzyl ester, polyalanine) with biological compatibility, and adopting ion exchange or ultrasonic emulsification process to obtain the invented nano hepatic target bio-degradable medicine carrier material. The hepatic target nano particle solution has good target performance for liver, the medicine enriched rate in the liver can be up to 75%, and its slowly-released administration can be up to above 15 days.

This application discloses phosphoramidate and phosphonoamidate prodrugs of alcohol-based therapeutic agents, such as nucleosides, nucleotides, acyclonucleosides, C-nucleosides, and C-nucleotides, and use of these prodrugs for treatment of diseases or disorders, including infectious diseases and cancers. This application also discloses a general method for enhancing bioavailability and / or liver-targeting property of alcohol drugs through converting the alcohol drugs to phosphoramidate or phosphonoamidate prodrugs, and methods of preparation of these prodrugs.

A sodium alginate liver-targeted nanometer drug delivery system uses sodium alginate as carrier material and uses glycyrrhetic acid as liver-targeted compound. The single-end-modified glycyrrhetic acid-ethylene diamine is prepared through the reacting between the carboxy group of glycyrrhetic acid and the ethylene diamine. The glycyrrhetic acid-sodium alginate is prepared through the reacting between the carboxy group of sodium alginate and the amino group of glycyrrhetic acid-ethylene diamine. Finally the sodium alginate liver-targeted drug delivery nanometer particles are prepared through crosslinking the glycyrrhetic acid-sodium alginate through calcium ions. The invention has a beneficial effect that the liver-targeted nanometer drug delivery system prepared by the invention has high liver targeting property. The hydrophilic anticancer drug and hydrophobic anticancer drug can be packaged simultaneously or a single anticancer drug is packaged. The sodium alginate liver-targeted nanometer drug delivery system of the invention has the advantages of sustained-releasing function of drug, reduced drug dosage, reduced drug taking times, reduced toxic-side effect of drug, increased drug effect, simple and practical preparing method, and excellent application prospect.

The invention relates to the field of biological medicine, and in particular relates to liver targeted medicine. The medicine is chemical micromolecular medicine connecting galactosamine. The chemicalmicromolecular medicine is medicine for treating liver diseases or liver-related diseases. The chemical micromolecular medicine is prepared from but not limited to thyroxine T3, sorafenib, taxol, regorafenib, lamivudine, entecavir, telbivudine, statins, fibrates, niacin, bile acid sequestrants, other hepatitis virus DNA (RNA) polymerase inhibition compounds and the like. The galactosamine is tervalent acetylgalactosamine. The connection is the direct connection of the galactosamine and the chemical micromolecular medicine or the connection through linking fragments; the linking fragments comprise but not limited to carbon chains, disulfide bonds, pyrophosphate diester, cysteic acid, polypeptide and thioether or valine-citrulline. The medicine provided by the invention has the advantages that the liver targeted performance is improved; the medicine curative effect is enhanced; the toxic and side reactions on other non-targeted tissues are few.

This disclosure relates to a low density lipoprotein-like cationic solid lipid nanoparticle targeting liver cells including parenchyma cells and non-parenchyma cells, a composition for liver target delivery, a composition for diagnosis and / or treatment of liver disease comprising the same, and a method for liver targeting of an active ingredient.

The invention relates to a drug delivery system of nanometer liver targeting amphiphilic block copolymer and a preparation method thereof. The nanometer liver targeting drug delivery system is obtained by adopting liver targeting amphiphilic block copolymer which can be biologically degraded and which has good biocompatibility as the carrier material and embedding drugs for treating liver diseases by a solvent dialysis method or a solvent evaporation method; the weight ratio of the carrier material to the drug is 1:0.1 to 1.2. The drug delivery system has the advantages of simple operation, mild condition and cheap raw material; the prepared drug delivery system has good biocompatibility and both effects of active targeting and passive targeting, and can realize high targeting and sustained release drug delivery to the liver by means of injection, thus solving the defects of bad targeting and low bioavailability of present anticancer drugs and improving the life quality of patients, with broad application prospects.

The invention relates to a new type of liver targeted drug carrier- glycyrrhetate modified chitosan / carboxylated chitosan compound drug carrier nanometer particle as well as its preparing method. The preparing procedure includes the following steps: dissolving the glycyrrhetate into carboxylated chitosan of a certain density; adding certain amount of chitosan solution which contains drug into the carboxylated chitosan while stirring; nanometer particles form automatically because of the electrostatic interaction among different molecules. The invention has simple preparing procedures, mile operating conditions and it has no poisoning or side effects of the organic solvents. Since the glycyrrhizin has characteristic of targeting at the liver, the product in the invention has the function of active targeting which leads to high effect liver targeting capabilities. The invention is applicable to the entrapment of medicine that contains electrical group (such as doxorubicin hydrochloride), protein drugs and medicine that has certain water-solubility in neutral pH conditions.

The present invention relates to hydrophobic modified preS-derived peptides of hepatitis B virus (HBV) which are versatile vehicles for the specific delivery of compounds to the liver, preferably to hepatocytes, in vitro as well as in vivo. Any kind of compound, but in particular drugs, such as interferons, viral reverse transcriptase inhibitors or core assembly inhibitors, and / or labels can be specifically targeted to the liver and so be enriched in the liver. This liver targeting can further be used for the targeted diagnosis, prevention and / or treatment of liver diseases or disorders, such as hepatitis, malaria, hepatocellular carcinoma (HCC), as well as for the prevention of HAV, HBV, HCV and / or HDV infection. The present invention relates to pharmaceutical compositions comprising said hydrophobic modified preS-derived peptide(s) and the compound(s) to be specifically delivered to the liver. The present invention furthermore relates to a method for the combined treatment of a liver disease and the prevention of HAV, HBV, HCV and / or HDV infection. The present invention relates also to the use of the preS-derived peptides in gene therapy and the delivery of immunogenic epitopes for hepatocyte-mediated antigen presentation to activate liver-directed immunological responses.

The invention belongs to the medical field, and specifically, relates to a novel glycyrrhetinic acid-modified lipid, a liver targeting liposome, a micelle and a compound, and their preparation method. The novel glycyrrhetinic acid-modified lipid contains glycyrrhetinic acid as a liver targeting mediating material, and is utilized as a membrane material of a liposome or a micelle to enable the liposome or the micelle to have liver targeting activity. Specifically, the novel glycyrrhetinic acid-modified lipid is prepared from raw materials of glycyrrhetinic acid and a phosphatide or cholesterol by a reaction in a condensing agent-containing solvent. The invention also provides a liver targeting liposome carrier and a liver targeting micelle carrier mediated by glycyrrhetinic acid. The liver targeting liposome carrier is prepared from the novel glycyrrhetinic acid-modified lipid, cholesterol and a phosphatide. The liver targeting micelle carrier is prepared directly from the novel glycyrrhetinic acid-modified lipid. The invention also provides a liver targeting liposome compound or a liver targeting micelle compound comprising an encapsulation layer of the liver targeting liposome carrier and the liver targeting micelle carrier. Therefore, glycyrrhetinic acid mediation-related drugs can be targeted to hepatic cells; toxicity of the glycyrrhetinic acid mediation-related drugs on normal tissue is reduced; and drug effects of prevention and treatment of liver complaints are improved.

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 galactosamine and polydopamine modified liver cancer targeting nanoparticles as well as a preparation method and application thereof. The preparation method of the galactosamine and polydopamine modified liver cancer targeting nanoparticles comprises the following steps: taking polymer and a hydrophobic medicine, dissolving the polymer and the hydrophobic medicine into an organic solvent, stirring, dropwise adding the obtained solution into TPGS aqueous solution, stirring, carrying out reduced pressure volatilization, centrifuging, and abandoning supernate, so that polymer initial nanoparticles carrying the hydrophobic medicine are obtained; resuspending the initial nanoparticles in Tris buffer solution, adding dopamine hydrochloride for reacting, and centrifuging, so that hydrophobic-medicine-carrying nanoparticles wrapped by polydopamine are obtained; dispersing the hydrophobic-medicine-carrying nanoparticles wrapped by polydopamine into weakly alkaline aqueous solution, adding a liver cancer targeting ligand galactosamine, reacting, centrifuging, and carrying out freeze drying, so that the galactosamine and polydopamine modified liver cancer targeting nanoparticles are obtained. The preparation method of the galactosamine and polydopamine modified liver cancer targeting nanoparticles is simple and pollution-free; and the galactosamine and polydopamine modified liver cancer targeting nanoparticles have good liver targeting property, biological compatibility and biological degradability, can be used for targeting liver cancer and has treatment effect.

The invention provides a prodrug of a hepatitis b virus resistant drug with a liver targeting action and a preparation method for the same. The prodrug is a prodrug of Adefovir or Tenofovir. Higher fatty acid, glyceride, cholic acid compounds or the base groups of derivatives thereof with the liver targeting action are connected with Adefovir or Tenofovir to prepare the prodrug. After being taken into a human body, the prodrug is concentrated in the liver and then is decomposed, thereby having the effects of reducing the dosage, improving the curative effect, reducing the drug concentration in a kidney and reducing the toxic and side effect. The invention also provides a method for synthesizing the prodrug.

The invention discloses cantharidin vesicles and a preparation method thereof, and a preparation containing the cantharidin vesicles and a preparation method thereof, and belongs to the field of pharmaceutical preparations. The cantharidin vesicles are prepared from cantharidin, a nonionic surfactant and an additive and are preferably prepared into an external gel preparation. A cantharidin percutaneous delivery external preparation has unique advantage over the medicament and is applied to a novel vesicle administration system, so that the percutaneous absorption of the medicament is increased, the clinical curative effect is enhanced, and the cantharidin percutaneous delivery external preparation can be used for treating cancer, specifically liver cancer, and has a liver targeting effect.

The present invention discloses an adefovir dipivoxil cholic acid class derivative and also relates to a preparation method and applications thereof at the medical aspect. The adefovir dipivoxil cholic acid class derivative is a hepatic targeting precursor drug of adefovir; compared with the adefovir dipivoxil, the adefovir dipivoxil cholic acid class derivative can improve the concentration of the adefovir in liver after being taken orally, and the adefovir dipivoxil cholic acid class derivative can be used as a preferential drug for the treatment of resisting virus and especially resisting hepatitis virus.

The invention relates to a pH sensitive type liver-targeted compound nano drug delivery system based on sodium alginate and a preparation method. The system is prepared by blending a liver-targeted carrier GA-ALG-mPEG or GA-ALG and a pH sensitive type drug carrier DOX-ALG-mPEG or DOX-ALG proportionally in a mode of dialysis through self assembly. The preparation of the material comprises a sodium alginate derivative (ALG-mPEG), the liver-targeted carrier and the pH sensitive type drug carrier. By the modification of the hydrophilic mPEG according to the compound nano drug delivery system, the non-specific adsorption with cells and protein can be effectively avoided. Meanwhile, the capabilities of drug loading and ligand targeting of the material are enhanced. The pH sensitive type liver-targeted compound nano drug delivery system based on the sodium alginate has the function of liver targeting. Meanwhile, the drug release of a fixed point at the part of a tumor can also be realized according to the difference of pH at normal tissues and the part of the tumor so as to enhance the curative effect and lower the side effect of drugs. The preparation method is simple, is easy to amplified production and has favorable application prospect.

A synthesis of the liver-target formate derivative containing galactose structure and its preparation containing said derivative are disclosed. Said derivative is prepared through the esterifying reaction sterol or emtrol and the compound containing lactose structure by di-primary amine compound in organic solvent other than water. It can modify the liposome, emulsion, milimicron vesicle (particle) and micelles to improve the liver-targeting performance.

The invention relates to a lactose acidized glycyrrhetinic chitosan material and a preparation method and the application thereof. The lactose acidized glycyrrhetinic chitosan material is a glycyrrhetinic acid and lactobionic acid jointly modified chitosan material which is synthesized through N-acylation reaction with chitosan serving as carrier and glycyrrhetinic acid and lactobionic acid serving as ligands. The invention further provides a lactose acidized glycyrrhetinic chitosan / 5-fluorouracil medicine carrying nano particle. The lactose acidized glycyrrhetinic chitosan material and the preparation method and the application thereof have the advantages that the dual-ligand co-modified chitosan material is synthesized for the first time, and the nano particle is prepared for target research; and the lactose acidized glycyrrhetinic chitosan which is prepared into the nano particle has higher liver targeting performance and hepatoma cell receptor mediate initiative targeting performance as compared with GA (glycyrrhetinic acid )-CTS (chitosan) and CTS, distribution in other visceral organs can be evidently reduced, reliability in hepatoma targeting is improved, and the lactose acidized glycyrrhetinic chitosan material can be used as a carrier material which has wide application prospect in clinical hepatoma targeted treatment.