39results about How to "Increase the maximum tolerated dose" patented technology

Methods for the treatment of CNS disorders using combinations of muscarinic activators and inhibitors, and medicaments comprising muscarinic activators and inhibitors.

Methods for the treatment of CNS disorders using combinations of muscarinic activators and inhibitors, and medicaments comprising muscarinic activators and inhibitors.

Methods for the treatment of CNS disorders using combinations of muscarinic activators and inhibitors, and medicaments comprising muscarinic activators and inhibitors.

The invention belongs to the technical field of medicinal chemistry, and specifically relates to a naphthalimide indole heterocyclic compound, a preparation method and application thereof. The naphthalimide-indole heterocyclic compound of the present invention has good antitumor activity, and its antitumor activity in vivo and in vitro is better than that of naphthalene, and the antitumor spectrum is wider. Different from the classic amafite, the compound of the present invention targets the key enzyme PAO (polyamine oxidase) in the tumor polyamine microenvironment and three endogenous small molecules Put (putrescine), Spd (spermidine ) and Spm (spermine) content, regulate subcellular organelles and nuclear function to reverse drug resistance, and at the same time enhance anti-tumor immune response, and have good therapeutic potential for advanced metastatic tumors. The complex of the present invention also solves the problems of poor solubility, cumbersome clinical compatibility and poor immunity of patients in the clinical application of chemotherapeutic drugs of naphthalimide analogues represented by naphthalene in the past, and has good water solubility.

The invention belongs to the technical field of medicinal chemistry, and in particular relates to a tetravalent platinum naphthalimide complex, its preparation method and application. The tetravalent platinum naphthalimide complex of the present invention has good antitumor activity, and its antitumor activity is better than that of cisplatin and oxaliplatin, and it is compatible with cisplatin, carboplatin, oxaliplatin, etc. The valence platinum is relatively stable. In the present invention, tetravalent platinum modified by naphthalimide has better targeting to tumor cells, and improves the high selectivity to tumor cells. Different from classic divalent platinum drugs, the complexes of the present invention pass Targeting the high polyamine microenvironment of the tumor to regulate subcellular organelles and nuclear functions reverses drug resistance, and at the same time relieves the immune suppression of T cells around the tumor. The complex of the present invention also solves the problems of poor solubility of divalent platinum-based antitumor drugs, cumbersome clinical compatibility, poor immunity of patients in clinical application of chemotherapeutic drugs, etc., and has good fat solubility and water solubility.

The present invention relates to the field of biotechnology, in particular to a specific targeting polypeptide self-assembled nanoparticle, the nanoparticle comprises a therapeutic amount of a hydrophobic antitumor drug, and two self-assembly methods wrapped around the hydrophobic antitumor drug. An affinity polypeptide, the amphiphilic polypeptide is a targeting peptide that can specifically target tumor cell epidermal growth factor receptor, and the N-terminus of the targeting peptide is coupled with a hydrophobic functional molecule. After targeting tumor cells, the nanoparticles expose targeting peptides, target tumor cells, enter tumor cells through receptor-mediated endocytosis, release drugs, inhibit DNA synthesis and repair, and perform double killing on tumor cells , inhibit tumor growth. The amphiphilic polypeptide does not generate covalent bonds and has no reverse reaction during the self-assembly process, and has the advantages of non-toxicity and good biocompatibility for tumor treatment.

The invention provides an active targeting type amphipathic polypeptide nano-drug carrier and preparation and application thereof, and belongs to the technical field of biological medicines. According to an amphipathic polypeptide, an alkyl chain serves as the hydrophobic end, a polypeptide chain with active targeting functional and side chain modification fluorescent functional molecules serves as the hydrophilic end, and an anti-tumor drug is wrapped in a hydrophobic cavity of a micelle formed by self-assembling the amphipathic polypeptide. The nano-carrier can actively target tumor cells and enter the tumor cells through receptor-mediated endocytosis, the amphipathic polypeptide and phospholipid molecules have strong interaction, and the phagocytosis of a nano-drug by tumor cells is promoted. In the process, tracing can be conducted through fluorescent imaging of fluorescent functional molecules modified on the polypeptide chain, and the tumor imaging aim is realized. Finally, the anti-tumor drug is slowly released to kill tumor cells and restrain the growth of tumors. The amphipathic polypeptide nano-carrier is free of toxin, high in biocompatibility and remarkable in anti-tumor efficiency, and the tumor diagnosis and treatment can be integrated.