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

The present invention is directed to therapeutic compositions targeting the NCCa-ATP channel of an astrocyte, neuron or capillary endothelial cell and methods of using same. More specifically, agonists and antagonists of the NCCa-ATP channel are contemplated. The therapeutic compositions are used to treat cancer, more specifically, a metastatic brain tumor, wherein a tumor-brain barrier is present. Such treatments are contemplated in combination with conventional anti-cancer therapies. Alternatively, the compositions are used to prevent cell death and to treat cerebral edema that result from ischemia, due to interruption of blood flow, to tissue trauma or to increased tissue pressure.

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.

According to the invention, one or more cysteine residues or cysteine derivative residues are used as a drug connection carrier; one or more drugs are coupled to limited connecting sites of the antibody at the same time, so that drugs with higher drug loading capacity are prepared or drugs with lower toxicity can be selected to prepare ADC products, and ADC products with larger treatment windows are 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 antibody drug conjugates with the same DAR value. 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 provides a stable polypeptide inhibitor for targeting HDAC. The amino acid sequence structure of the stable polypeptide inhibitor is shown in specification. The invention also provides application of the stable polypeptide inhibitor targeting HDAC in preparation of a drug for inhibiting the enzymatic activity of HDAC family. The invention also provides application of the stable polypeptide inhibitor targeting HDAC in preparation of a drug for inhibiting tumor stem cells with high expression of HDAC1. The invention further provides application of the stable polypeptide inhibitor targeting HDAC in preparation of a drug for treating human ovarian teratoma or testicular embryonic carcinoma. Experiments of cell proliferation, apoptosis and cell cycle arrest prove that the polypeptide can effectively inhibit proliferation of the tumor stem cells, and the polypeptide has no obvious tissue damage or toxicity to mice at a high dose.

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 drug conjugate with multiple targeting ligands having a cell endocytosis mediating function. The drug conjugate consists of drug molecules and connexons coupled with the drug molecules; the drug conjugate at least comprises two or more ligands which can be specifically bound to cell surface receptors; the ligands at least include one first ligand which has the cell endocytosis mediating function; and at least one of the ligands and the first ligand are coupled and then are selectively coupled with the drug molecules or the connexons so as to form the drug couplet. The drug conjugate provided by the invention has the beneficial effects that by combining targeting and endocytosis structures, polypeptide, which is targeted by any ligands, is taken as a guiding part, so that the targeting scope of the like medicines is widened. The affinity and the targeting performance of the drug conjugate on diseased cells can be enhanced by virtue of the multiple targeting ligands, so that efficient toxin drugs such as MMAE can be carried, efficacy can be enhanced, a therapeutic window can be widened and side effects of the medicines can be avoided.

The invention relates to a sulfonium salt stable targeting HDAC polypeptide drug conjugate and application thereof, a sulfonium salt stable apoptosis-promoting polypeptide is coupled with an HDAC inhibitor to form a stable polypeptide HDAC inhibitor with tumor selective toxicity, the nonspecific toxicity of apoptosis polypeptide chemically stabilized by sulfonium salt is remarkably reduced, the stability of protease is higher, and the tumor selective toxicity of the apoptosis polypeptide is remarkably reduced. When a polypeptide drug conjugate is formed by coupling with an HDAC inhibitor, the polypeptide drug can significantly improve the selective toxicity to tumor cells, and has weak toxicity to normal cells. Cell proliferation, cell apoptosis and cell cycle arrest experiments prove that the polypeptide can effectively inhibit proliferation of malignant liver cancer, has relatively good biological safety and has a potential anti-tumor clinical application prospect.

The invention discloses an aconitine injection for intrathecal injection and a preparation method thereof. Aconitine refers to a compound with a structural feature in the formula shown in the description, wherein R1-R18 represent H or OH or X or OX, the X comprises Me, Ac, Bzl, a para methoxyphenyl formyl group and an o-acetamido benzoyl group, but not limited to the groups. The dosage of the aconitine injection ranges from 0.02 mg to 20 mg per bottle, and the aconitine injection is used for treating pain; the preparation forms comprise the injection, a freeze-dried powder injection, a prefilled injection and the like which are delivered through injection; the dosage is decreased to about one-tenth of original dosage, the toxic and side effects are greatly reduced, and the safety window and the therapeutic index are increased, processing of an aconitine preparation is completed through a low-temperature technology at the temperature lower than 50 DEG C, impurities produced through high-temperature hydrolysis of the aconitine are avoided, and therefore qualified products can be produced in a batched mode.

The invention discloses a method for developing an intelligent cancer drug, which belongs to the field of biomedicine and is a method for developing the intelligent cancer drug. According to the scheme, the drug is specifically activated in tumor tissues through design modification, so that systemic toxic diseases of the drug are reduced to widen the treatment window of the drug; tissue specificity is utilized to improve the targeting property of the drug, so that the induced differentiation capability of differentiated drugs on tumor cells is improved, or the toxicity of anticancer drugs on cancer cells is improved; and a liposome is taken as a drug carrier, so that the drug has the advantages of maintaining the drug activity, enhancing the drug solubility, reducing the effect on normal tissues and the like. The technology can be applicable to auxiliary targeted treatment of multiple cancers, and has a wide application prospect.

The present invention discloses a targeting ligand-drug conjugate having a cell endocytosis mediating function. The targeting ligand-drug conjugate comprises a drug molecule and a linker coupled to the drug molecule, and is characterized by further comprising a molecule having a mediating effect and a ligand specifically bound to a cell surface receptor, wherein the ligand is a polypeptide or small molecule ligand, and the molecule can be coupled to the ligand, can be coupled to the drug molecule or linker to form the drug conjugate, or is respectively and separately coupled to one of the drug molecule and the linker to form the drug conjugate. According to the present invention, with the combination of the targeting and the endocytosis (transmembrane) structure, the any ligand targeting polypeptide can be adopted as the leader so as to broaden the targeting range of the drug; and with the conjugate, the stability of the drug during the in vivo circulation is ensured, and the drug toxicity is reduced.

The invention discloses an application of compound omeprazole in the preparation of information treatment drug, a preparation method of the compound omeprazole, and a prepared novel drug. The information treatment drug is characterized in that the drug is not contacted with a human body directly in the treatment, the substance ingredient of the drug cannot be consumed, only the drug information is used for physical treatment, and the chemical treatment effect can be achieved, a treatment window is enlarged by more than 1000 times, and the side effects of the chemical treatment are avoided. After the omeprazole is used as the information treatment drug, the contents of active ingredients are not changed, and the omeprazole can be used as the conventional preparation of the chemical treatment for secondary effective use.

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 disclosure provides means and methods for interfering with Programmed Cell Death 1 protein (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) mediated inhibition in a PD-1 and / or TIM-3 positive cell. A method may comprise contacting said cell with an antibody or a functional part, derivative and / or analogue thereof that comprises a variable domain that can bind to an extracellular part of PD-1 and a variable domain that can bind to an extracellular part of TIM-3, thereby inhibiting PD-1 and / or TIM-3 mediated activity in said cell. The invention also provides antibodies or variants thereof that comprises a variable domain that can bind to an extracellular part of PD-1 and a variable domain that can bind to an extracellular part of TIM-3.

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 invention discloses an application of a glibenclamide compound in preparation of an information therapy medicament, a method for preparing the information therapy medicament, and a novel drug prepared with the method. The information therapy medicament is not in direct contact with a human body during treatment, the components of the medicament is not consumed, only medicament information is utilized for physical therapy, so that the chemical treatment effect can be achieved, the therapeutic window is enlarged by more than a thousand times, and the side effect of chemical treatment is avoided. After the glibenclamide is used as the information therapy medicament, the content of effective components of the glibenclamide is not changed, so that the glibenclamide can be used as a conventional preparation in chemical treatment for secondary effective use.

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.

Multi-specific binding proteins that bind a tumor associated antigen, the NKG2D receptor, and CD 16 are described, as well as pharmaceutical compositions and therapeutic methods useful for the treatment of cancer.

The invention discloses application of a desloratadine compound in preparing an information medicine, a preparation method of the information medicine by the desloratadine compound and a novel drug prepared by the preparation method. During the treatment, the information medicine does not directly touch a human body, drug substance components are not consumed, chemotherapy effects can be achieved only by utilizing drug information physiotherapy, and the therapy window is enlarged by more than one thousand times, and side effects of the chemotherapy are avoided. After desloratadine is used as the information treatment drug, the effective component content is not changed, and desloratadine can be used secondarily and effectively as a chemotherapy normal preparation.

The invention discloses application of an allopurinol compound in preparing an information treatment drug, a preparation method of the allopurinol compound and a novel drug prepared by the preparation method. During the treatment, the information treatment drug does not directly touch a human body, drug substance components are not consumed, chemotherapy effects can be achieved only by drug information physiotherapy, and the therapy window is enlarged more than one thousand times, and side effects of the chemotherapy are avoided. After allopurinol is used as the information treatment drug, the effective component content is not changed, and allopurinol can be used secondarily and effectively as a chemotherapy normal preparation.

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 invention discloses application of ambroxol hydrochloride in the preparation of an information therapeutic drug, a preparation method of the ambroxol hydrochloride and a novel drug prepared by the preparation method. The information treatment drug is characterized in that the drug does not contact a human body directly in the treatment, any substance ingredient of the drug can not be consumed, only the drug information is utilized for physical treatment, but the chemical treatment effect can be achieved, a treatment window is enlarged by more than 1000 times, and the side effects of the chemical treatment are avoided. After the ambroxol hydrochloride is used as the information treatment drug, the contents of active ingredients are not changed, and the ambroxol hydrochloride can be used as the conventional preparation in the chemical treatment for secondary effective use.

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 relates to application of composition Xiaoke pills to preparation of an information intervention agent, a preparation method of an information intervention body and a product . The composition Xiaoke pills achieve an intervention effect by performing the reaction on Xiaoke pill information and a human body information receptor and adopting a Xiaoke pill information physical method without being used as a plant chemical treatment medicament. Therefore, after the Xiaoke pills are used as the information intervention body, the Xiaoke pill material is not consumed for the information intervention, so that the quality of the Xiaoke pills is not influenced and the Xiaoke pills also can be effectively reused as a plant chemical treatment conventional preparation.

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 discloses an application and a preparation method of a compound madopar to preparation of an information therapeutic medicine and a novel medicine prepared from the compound madopar. The information therapeutic medicine is indirect with a human body during therapy, so that material components of the information therapeutic medicine cannot be consumed, a chemical treatment effect can be achieved by only using medicine information physical therapy; and a therapy window of the information therapeutic medicine is enlarged by above thousands, and thus side effects of chemical therapy are avoided. After the madopar is used as the information therapeutic medicine, contents of effective components are not changed, and the information therapeutic medicine can be used as a chemical therapeutic conventional preparation to be secondarily and effectively used.

The invention discloses a prodrug compound of a dithiocarbamic acid metal complex as well as a preparation method and application of the prodrug compound. According to the prodrug compound disclosed by the invention, dithiocarbamic acid and metal ions can be carried in a single small molecule at the same time, and the dithiocarbamic acid and the metal ions are kept in an inert state; under specific conditions, the dithiocarbamic acid prototype is triggered and released, the metal chelating function of the dithiocarbamic acid prototype is recovered, and the dithiocarbamic acid prototype and metal ions carried in molecules are subjected to intramolecular metal coordination reaction to form the dithiocarbamic acid metal complex with biological activity. The prodrug compound disclosed by the invention can realize selective in-situ activation of a metal complex, and has a good application prospect in tumor prevention and treatment and diseases related to abnormal metal ion metabolism; meanwhile, a feasible thought and a feasible method are provided for the prodrug design of the metal coordination type drug.