15 results about "Melphalan" patented technology

The invention belongs to the technical field of biological medicines, and particularly discloses application of a POLQ inhibitor in treatment of multiple myeloma. The invention relates to an application of a POLQ inhibitor in preparation of a medicine for improving the Melphalan treatment sensitivity of multiple myeloma, an application of Melphalan combined with the POLQ inhibitor in preparation of a medicine for treating multiple myeloma, and a medicine composition containing Melphalan and the POLQ inhibitor and used for treating multiple myeloma. The invention also relates to an application of a preparation for detecting the expression level of POLQ in preparation of a product for detecting the killing effect of multiple myeloma cells for resisting melphalan and an application of high-expression POLQ in preparation of a biological model for resisting treatment of multiple myeloma melphalan. The POLQ inhibitor can significantly enhance the therapeutic effect of melphalan, so that the problem that the curative effect excessively depends on dosage when melphalan is independently applied is avoided, the problem that multiple myeloma is poor in response to single melphalan can also be solved, and a new thought is provided for development of a multiple myeloma combined treatment strategy.

The present application for a patent of invention relates to the use of melphalan in the preparation of an intravitreal medicament for the prevention of vitreoretinal proliferation. It belongs to the technical field of pharmaceuticals, particularly ophthalmic medicines, and comprises melphalan at a concentration of 5 μg / 0.1 mL, intended for intravitreal injectable administration during pars plana vitrectomy.

The present invention belongs to the field of biomedicine and specifically discloses the use of POLQ inhibitors in the treatment of multiple myeloma. This disclosure relates to the use of POLQ inhibitors in the preparation of drugs that enhance the sensitivity of multiple myeloma to melphalan treatment, the use of melphalan combined with a POLQ inhibitor in the preparation of drugs for treating multiple myeloma, and drug combinations comprising melphalan and a POLQ inhibitor for treating multiple myeloma. It also relates to the use of preparations for detecting POLQ expression levels in the preparation of products for detecting the resistance of multiple myeloma cells to the cytotoxic effects of melphalan, and the use of highly expressed POLQ in the preparation of biological models for melphalan-resistant multiple myeloma. The POLQ inhibitors disclosed in this disclosure can significantly enhance the therapeutic effect of melphalan, thereby avoiding the excessive dose dependence of efficacy when melphalan is used alone. They can also address the problem of multiple myeloma patients' poor response to melphalan alone, providing new insights into the development of combination therapy strategies for multiple myeloma.

The invention discloses a eeFISH (fluorescence in situ hybridization) whole brain tissue transparentizing multiple fluorescence in situ hybridization method and a kit. The hybridization method comprises the steps of whole brain tissue perfusion fixation, decoloration, nucleic acid anchoring, hydrogel crosslinking, electrophoresis-driven transparentizing, probe permeation through osmotic pressure regulation, electrophoresis hybridization and the like. The method specifically comprises the following steps: 1) carrying out covalent anchoring on nucleic acid through a melphalan-succinimide ester compound, and carrying out three-dimensional cross-linking immobilization with an acrylamide-bisacrylamide hydrogel system so as to maintain tissue molecule information and a space structure; (2) molecules such as lipid are removed through electrophoresis, and rapid tissue transparentizing is achieved; and 3) promoting the probe to permeate into the deep layer of the tissue and specifically hybridize under osmotic pressure and electrophoresis conditions. According to the application, high-efficiency electrophoresis driving and osmotic pressure regulation are taken as core characteristics, in-situ detection of whole-brain three-dimensional space molecular information can be directly, efficiently and quickly realized, and the problems of difficulty in compatibility of transparency and hybridization, slow probe permeation, insufficient signal background noise elution and the like are effectively solved; the method is widely applicable to space in-situ detection and analysis of nucleic acid and protein.

The present invention relates to a conjugate of cell-penetrating peptide and melphalan and a formulation comprising the same. Specifically, the present invention relates to a conjugate formed by covalently linking cell-penetrating peptide derivative to melphalan, a formulation comprising the conjugate, a method for treating diseases with the conjugate, and the application of the formulation in treating diseases.

The invention provides melflufen, or a salt thereof, or a pharmaceutical formulation comprising melflufen, or a salt thereof, for use in the treatment and / or prophylaxis of immunoglobulin light chain (AL) amyloidosis. The invention also provides dosage regimens and kits that find utility in the treatment and / or prophylaxis of AL amyloidosis, and methods for the treatment and / or prophylaxis of AL amyloidosis, and uses of melflufen, or a salt thereof, for the manufacture of a medicament for the treatment of AL amyloidosis.

The invention discloses a supramolecular polypeptide-drug coupled prodrug nano material for treating multiple myeloma as well as a preparation method and application of the supramolecular polypeptide-drug coupled prodrug nano material. According to the nano material, hyaluronic acid modified by beta-cyclodextrin is taken as a skeleton, and a melphalan-dexamethasone double-drug coupling compound coupled with an adamantane modified GFLG short peptide connexon is loaded through a supramolecular host-guest effect. The nano material has good stability and drug entrapment capacity under physiological conditions, and can realize quick-response drug release under the condition of simulating an enzymatic environment in myeloma cells. The nano material can realize efficient cellular uptake and specific drug activated release, so that proliferation of multiple myeloma cells is inhibited, and a new strategy for delivery of the multiple myeloma nano drug with a synergistic treatment effect is provided.

The invention is directed to stable, liquid pharmaceutical compositions comprising melphalan, at least one cyclodextrin, at least one non-aqueous solvent, water and / or at least one aqueous buffer, at least one antioxidant, optionally, at least one chelating agent, and, optionally, at least one inorganic salt. The invention is also directed to the use of the compositions of the invention for the treatment of cancers, their preparation, and dosage forms containing them.

The invention provides a melphalan targeted drug delivery system and a preparation method and application thereof, and the preparation method comprises the following steps: S1, dissolving rhodamine B in anhydrous tetrahydrofuran at-5-0 DEG C, and then slowly adding sodium borohydride until all hydrogen is released; s2, adding iodine, reacting for 8-10 hours, and quenching the reaction with water to obtain a first mixture; s3, extracting the first mixture for multiple times to obtain a solvent layer, drying, filtering, evaporating, purifying, separating and concentrating to obtain a first compound; s4, dissolving the melphalan and the first compound in anhydrous dichloromethane; s5, adding dicyclohexylcarbodiimide and 4-dimethylaminopyridine, and carrying out an esterification reaction so as to obtain a second mixture; and S6, washing, drying, filtering and evaporating the second mixture, purifying and separating, and concentrating to obtain a second compound. The melphalan targeted drug delivery system prepared by the invention can target tumor cells and tissues, can reduce the toxicity of the melphalan targeted drug delivery system to normal cells and tissues, and avoids serious side effects in a cancer treatment process.

The invention relates to a milobain transdermal delivery preparation which comprises the following components in percentage by weight: 8-12% of milobain or benzene sulfonate thereof (in terms of free alkali), 40-60% of an acrylic acid pressure-sensitive adhesive matrix, 8-12% of a polyvinylpyrrolidone crystal inhibitor, 9-22% of a solubilizer composition and 9-22% of a penetration enhancer composition, and the sum of the components is 100%. The preferable prescription of the transdermal drug delivery preparation has the following beneficial effects: (1) the crylic acid pressure-sensitive adhesive matrix is used as a drug carrying basis, and the crystal inhibitor is combined to effectively inhibit drug crystallization and separation, so that the long-term physical stability and uniformity of the preparation are ensured; (2) the solubilizing composition cooperates with the crystal inhibitor to maintain the supersaturated state of the medicine, so that the dissolving bottleneck of the miloabalin is overcome, and a foundation is laid for efficient transdermal release; (3) the penetration enhancer composition significantly improves the cumulative release rate, and shows excellent and stable penetration enhancing effect and long-acting release characteristic when being matched with different solubilizers; and (4) the adhesive force is moderate: the adhesive force of the preferable prescription is 9-14N, so that the adhesive strength and the comfort can be balanced, and the requirements of skin patches are met.

Pharmaceutical compositions comprising oil as a vehicle, a suspending agent, and a surfactant are disclosed to be used in conjunction with active pharmaceutical ingredients which are water soluble or insoluble, or which are sensitive to water but insoluble in oil. Such active pharmaceutical ingredients may include temozolomide, lenalidomide, Oxaliplatin, Cisplatin, Carboplatin, 5-fluorouracil, irinotecan, topotecan, cyclophosphamide, doxorubicin, vincristine, vinblastine, Melphalan, Chlorambucil, Dacarbazine, Daunorubicin, Epirubicin, Mitoxantrone, Etoposide, Teniposide, Azacitidine, Cytarabine, Gemcitabine, vinoralbine, Pemetrexed, a derivative thereof, or a combination thereof. The pharmaceutical compositions may be administered as an oral suspension. Other embodiments are directed towards methods of using and methods of making such formulations.

(3R, 4S)-3-(4-hydroxy-3,5-dimethoxyphenyl)-4-(4-hydroxyphenyl)-8-methyl-3,4-dihydro-2H- chromen-7-ol (TRX-E-002-1) for use in a method of treatment for a hematological cancer being acute myeloid leukemia or multiple myeloma in a subject in need thereof, the method comprising administering to the subject an effective amount of TRX-E-002-1. The method may further comprise administering to the subject an effective amount of a second compound selected from the group consisting of (i) a BCL-2 inhibitor such as venetoclax, navitoclax or obatoclax, (ii) a deoxycytidine analogue chemotherapeutic such as cytarabine or gemcitabine, (iii) a hypomethylating agent such as azacitidine or decitabine, (iv) an anthracycline chemotherapeutic such as daunorubicin, doxorubicin, epirubicin, idarubicin, valrubicin or mitoxantrone, (v) a proteasome inhibitor such as carfilzomib, bortezomib, and ixazomib, (vi) an immunomodulatory drug such as pomalidomide, lenalidomide, and thalidomide and(vii) a corticosteroid drug such as dexamethasone or prednisone, and (viii) an alkylator such as bendamustine, cyclophosphamide, melphalan, and melflufen. Corresponding combination pharmaceutical compositions.

The invention is directed to stable, liquid pharmaceutical compositions comprising melphalan, at least one cyclodextrin, at least one non-aqueous solvent, water and / or at least one aqueous buffer, at least one antioxidant, optionally, at least one chelating agent, and, optionally, at least one inorganic salt. The invention is also directed to the use of the compositions of the invention for the treatment of cancers, their preparation, and dosage forms containing them.

The invention discloses melphalan gel based on ultrasonic response as well as a preparation method and application of the melphalan gel. According to the preparation method disclosed by the invention, the melphalan hydrogel with a cross-linked nanofiber structure is rapidly formed by the melphalan under the ultrasonic action through non-covalent interaction. Melphalan hydrogels can be used to improve traditional HAIC treatment methods for liver cancer, including expediting catheter removal, reducing systemic toxicity, increasing local drug concentration, and prolonging drug-cell interaction time. In a rat model, the Melphalan hydrogel-assisted HAIC shows better effectiveness than the traditional HAIC, can significantly inhibit the growth of liver cancer, activates effective anti-tumor immune response, and realizes complete cure in part of liver cancer. In addition, the drug delivery capability of the melphalan hydrogel is expected to improve the pharmacokinetic characteristics of various drugs and promote the synergistic treatment effect of various drugs. Therefore, the invention provides a choice capable of obviously optimizing the treatment process and improving the overall treatment result for liver cancer treatment.

The invention discloses an active oxygen response type tumor diagnosis and treatment integrated microneedle patch and a preparation method and application thereof. The microneedle patch comprises a microneedle; the active oxygen response type prodrug FDOCl-19 comprises a phenothiazine structure, and the active oxygen response type prodrug FDOCl-19 is loaded on the microneedle. In a microenvironment with high ROS expression in a tumor area, FDOCl-19 is activated to release a large amount of anti-cancer drug melphalan and fluorophore methylene blue in a short time, melphalan effectively prevents growth of tumors, methylene blue can realize in-situ fluorescence imaging of the tumors, and the microneedle patch has the characteristics of on-demand drug delivery and high safety, and can be applied to the field of tumor treatment. And painless, noninvasive and precise treatment of superficial tumors is realized.