44results about How to "Expanding Therapeutic Window" patented technology

A novel combination comprising the MEK inhibitor N-{3-[3-cyclopropyl-5-(2-fluoro- 4-iodo-phenylamino)6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3- d]pyrimidin-1 -yl]phenyl}acetamide, or a pharmaceutically acceptable salt or solvate thereof, and / or a B-Raf inhibitor, particularly N-{3-[5-(2-Amino-4-pyrimidinyl)-2-(1,1 - dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide or a pharmaceutically acceptable salt thereof, and an anti-PD-L1 antibody; pharmaceutical compositions comprising the same and methods of using such combinations and compositions in the treatment of conditions in which the inhibition of MEK and / or B-Raf and / or neutralizing or inhibiting the interaction between PD-L1 and its receptor, e.g. PD-1, is beneficial, eg. cancer.

One or more cysteine residues or cysteine derivative residues are used as a drug connection carrier, and one or more drugs are simultaneously coupled on limited connection sites of an antibody, so that drugs with higher drug loading capacity or drugs with lower toxicity can be selected to prepare ADC products, and an ADC product with a larger treatment window is obtained. Furthermore, since a plurality of drug molecules can be coupled at one connection site, the ADC product obtained by the method provided by the invention has better uniformity under the condition of preparing an antibody drugconjugate with the same DAR value. moreover, the use amount of the antibody required in production can be greatly reduced, so that the production cost is effectively reduced. Compared with the antibody drug conjugate of which the same site can only be connected with one drug molecule, the antibody drug conjugate prepared by adopting the method disclosed by the invention still has the same inhibiting or killing effect on tumor cells under the condition that the total amount of the coupled drug molecules is greatly reduced.

The invention discloses a multi-drug-loading-point and high-drug-loading ligand-drug conjugate. The ligand-drug conjugate has a structure shown in general formula I, and has the characteristics of high loading capacity, high drug efficacy, low toxicity, and low risks. The ligand-drug conjugate can be particularly used for connecting a low toxicity drug molecule, thereby extending a therapeutic window. Furthermore, an antibody-conjugated drug molecule provided by the invention has the characteristics of multiple drug-loading points and high drug-loading capacity, and thus an antibody-conjugateddrug can carry a large amount of low toxicity drug molecules and achieve a therapeutic effect without depending on antibody targeting or high toxicity drugs. TM-{R<2>-PEG<1>-[R<1>-PEG<2>-(R<3>-A'-D)<n>]<m>}l(I).

An immunoconjugate having the Formula Ab-[L1-(A-L2-B)m]n, wherein: (a) Ab is an antibody or a binding fragment thereof; (b) L1 and L2 are each independently a linker, wherein L1 and L2 are the same ordifferent and wherein L1 links to L2; (c) A is a target-protein ligand / binder; (d) B is a ubiquitin ligase ligand / binder, and (e) n and m are independently integers from 1 to 8. The target protein includes kinase, G protein-coupled receptors, transcription factor, phosphatases, and RAS superfamily members.

The present invention discloses a targeting ligand-drug conjugate with cell endocytosis mediating function, the drug conjugate includes a drug molecule and a linker coupled with the drug molecule, characterized in that the The drug conjugates also include molecules with a mediating effect and ligands that specifically bind to cell surface receptors, the ligands are polypeptides or small molecule ligands, and the molecules and ligands can be coupled to each other, and It is coupled with a drug molecule or a linker to form a drug conjugate, or is separately coupled with one of the drug molecule and the linker to form a drug conjugate. The beneficial effects of the present invention are mainly reflected in: the combination of targeting and endocytic (membrane-penetrating) structures, so that any ligand-targeting polypeptide can be used as a guiding part, thereby broadening the targeting range of such drugs. The conjugate ensures the stability of the drug in circulation in the body and reduces the toxicity of the drug.

Disclosed are pharmaceutical compositions containing a cyclodextrin and a therapeutically effective amount of a glycopeptide antibiotic or a salt thereof. Also disclosed are methods of treating a bacterial disease in a mammal by administering such pharmaceutical compositions.

The present invention describes the modification of polypeptides, more particularly channel proteins with a thiol reactive agent so as to introduce an azide group. The present invention further describes vesicles comprising channel proteins modified according to the invention, which upon reaction with a phosphine open up thereby releasing the content of the vesicles. The reagents, polypeptides and vesicles described in the present invention have in vivo and in vitro applications in both drug delivery and imaging.

The invention specifically relates to a silk fibroin antibacterial dressing loaded with silver on one side, a preparation method and application thereof. Silver has good antibacterial properties and can be added to antibacterial agents on wounds, but studies have shown that silver may also have cytotoxicity and reduce wound cell viability. In view of the above technical problems, the present invention provides a silk fibroin antibacterial dressing with unilateral loading and in-situ generation of AgCl particles. The antibacterial dressing includes a silver-loaded layer and a silk fibroin layer. Provide a good growth environment, at the same time, the silver-loaded layer continuously releases Ag through the buffering effect of the silk fibroin layer + , while reducing cytotoxicity to the wound surface, it also acts as an antibacterial agent. The antibacterial dressing has the advantages of simple preparation process and promotion of wound healing.

The invention provides a nanoparticle with effect-enhancing and toxicity-reducing effect on synergistic and attenuating effects on annonaceous acetogenins drugs, and belongs to the field of pharmaceutical preparations. The present invention uses poloxamer P188, Poloxamer P407, Poloxamer P124, one or more of poloxamer P237 and poloxamer P338 are adjuvants, By limiting the kinds and dosage of excipients, the problems of insoluble and difficult administration of annonolactone are solved, and more importantly, the anti-tumor effect in vivo is improved, at the same time, it has better safety, breaks through the bottleneck problem of narrow window of treatment of annonolactone, and provides a feasible solution for clinical application.