18 results about "Lonidamine" patented technology

The invention belongs to the technical field of medicines, and discloses a lonidamine-entrapped tumor cell membrane bionic metal organic framework nanoparticle as well as preparation and application thereof. The preparation method comprises the following steps: firstly, preparing lonidamine-entrapped metal organic framework nanoparticles by adopting a one-pot method, then coating tumor cell membranes on the surfaces of the nanoparticles through repeated membrane extrusion or ultrasonic treatment, and finally preparing the lonidamine-entrapped tumor cell membrane bionic nano-drug. The preparation process is simple, the cost is low, the stability is good, and the repeatability is high. The bionic nano-drug disclosed by the invention is helpful for solving the problems of poor solubility, low bioavailability and the like of an anti-cancer drug lonidamine. And meanwhile, the tumor cell membrane camouflage technology can promote the nano-drug to realize relatively high tumor tissue accumulation by utilizing the dual effects of EPR passive targeting effect and homologous active targeting, so that the anti-tumor effect is improved, and the toxic and side effects of lonidamine are reduced.

The invention relates to a pharmaceutical composition for treating acute myelogenous leukemia. The pharmaceutical composition comprises lonidamine and a GPX4 inhibitor. The invention also relates to application of the pharmaceutical composition in preparation of drugs for resisting acute myelogenous leukemia cells. Aiming at an oxidation-antioxidation defense system of AML tumor cells, lonidamine and the GPX4 inhibitor are creatively combined for use, the inhibition rate of lonidamine and the GPX4 inhibitor on the AML cells is remarkably higher than that of independent medication, and the combination of lonidamine and the GPX4 inhibitor can synergistically inhibit the activity of the AML cells, induce mitochondria damage of the AML cells and promote ferroptosis of the AML cells, so that the purpose of treating the AML is achieved.

The invention relates to the technical field of biology, in particular to application of lonidamine combined with apigenin to treatment of colorectal cancer. The invention provides a novel pharmaceutical composition for treating colorectal cancer. LND and AP form the pharmaceutical composition according to different molar concentrations or different weight ratios, the anti-tumor activity of the pharmaceutical composition is respectively tested on a colon cancer cell line MC38 culture and a tumor-bearing mouse, and results prove that compared with the effect of a single drug, the combined drug obviously improves the activity of anti-tumor cells in vitro or in vivo.

The invention discloses a ternary carrier-free nanoparticle as well as a preparation method and application thereof. The ternary carrier-free nanoparticles comprise nanoparticles which are formed by the chlorine e6, the lonidamine and the RG108 through an intermolecular interaction force. The nanoparticles can improve effective absorption and accumulation of drugs in tumors, can induce tumor specific pyroptosis and immunogenic effect under laser irradiation, and can promote maturation of antigen presenting cells and recruitment and activation of cytotoxic T lymphocytes, thereby starting adaptive anti-tumor immunity.

The invention discloses a nucleolin aptamer modified carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system as well as a preparation method and application thereof, and relates to the field of tumor treatment. The nucleolin aptamer AS1411 is coupled with glycolysis regulation nano-particles through covalent bonds, and the carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system comprises a carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system, a carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system and a carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system, the glycolysis regulation nano-particles take carboxymethyl chitosan as a carrier skeleton, the carrier skeleton is loaded with a lonidamine derivative through grafting modification, and the nano drug delivery system can synchronously entrap paclitaxel. According to the invention, a synergistic treatment system integrating active targeting, metabolic regulation and chemotherapy is constructed, and by virtue of a multi-mechanism synergistic effect, an antitumor drug for inhibiting tumor cell activity, glycolysis or tumor metabolism reprogramming is prepared; the huge potentials of overcoming the drug resistance bottleneck of traditional chemotherapy, enhancing the curative effect and reducing the toxic and side effects are shown.

The invention discloses a pharmaceutical composition for inhibiting the activity of fusarium solani and application of the pharmaceutical composition. The active ingredients of the pharmaceutical composition are composed of plant essential oil cinnamyl aldehyde and hexokinase inhibitor lonidamine. Wherein the essential oil cinnamyl aldehyde is used as a main bacteriostatic agent, and the hexokinase inhibitor lonidamine is used as a synergistic bacteriostatic agent. Based on the characteristic that cinnamyl aldehyde exerts the bacteriostatic activity by interfering glycometabolism, the bacteriostatic activity of the natural product cinnamyl aldehyde is effectively improved by combining with hexokinase inhibitor drug combination, and potential drugs and medication strategies can be provided for treatment of fungal keratitis caused by fusarium solani.

This invention discloses a ternary nanoparticle, its preparation method, and its applications, relating to the field of biomedical technology. The invention constructs a carrier-free, fully active ternary nanoparticle (diPCL NPs). This nanoplatform connects PTX dimer (diPTX), celecoxib (CXB) dimer (diCXB), and lonidamine (LND) dimer (diLND) via disulfide bonds for chemoimmunotherapy of drug-resistant tumors. diPCL NPs accumulate at tumor sites through enhanced permeability and retention (EPR) effects and circulate continuously in the bloodstream. In the high GSH tumor microenvironment, disulfide bond cleavage releases the active drug, exerting chemotherapeutic, immune-activating, sensitizing, and metabolic-regulating effects. diPCL NPs exhibit high antitumor efficacy and good safety profile within the therapeutic window in both breast cancer and paclitaxel-resistant models.

The application discloses a nano-focal anaphylaxis drug targeting CD47 protein and preparation and application thereof, and belongs to the technical field of drugs. The nano-focal anaphylaxis drug is a micellar nanoparticle formed by self-assembly of an amphiphilic carrier material and a focal anaphylaxis prodrug, the amphiphilic carrier material is composed of an amphiphilic polymer with a hydrophilic end modified with a CD47 targeting peptide and an amphiphilic polymer without modification, and the focal anaphylaxis prodrug is a prodrug formed by reduction response chemical bond connection of lonidamide or 3-bromopyruvic acid. The nano-focal anaphylaxis drug provided by the application can realize precise tumor treatment, the CD47 targeting peptide realizes efficient targeted delivery and accumulation of the drug in the tumor, the release of the focal anaphylaxis prodrug is triggered by higher reduction medium level in tumor tissues, and tumor cells are induced to undergo focal anaphylaxis. In normal tissues, the nano drug cannot induce normal cell focal anaphylaxis, and therefore the tumor selectivity of the nano drug is significantly enhanced.

The invention relates to a membrane fusion liposome delivery system and a preparation method and application thereof, and belongs to the technical field of liposome preparation. The invention provides a membrane fusion liposome delivery system. The system takes lipidosome as a carrier, the surface of the lipidosome is modified with cRGD targeting molecules, and the interior of the lipidosome is loaded with a TPP-modified antitumor drug lonidamine; a DNA device CLTD is anchored on a liposome membrane through cholesterol, and the device is formed by a short-chain CAP containing an APE1 restriction enzyme cutting site and a long-chain LTD containing a CD63 aptamer and a RelA aptamer through base complementary pairing. The APE1 enzyme highly expressed in a tumor microenvironment is used as a specific trigger signal, and precise activated release of the drug in tumor cells and space-time controllable degradation of RelA protein are achieved. According to the system, chemical drug inhibition and nucleic acid aptamer mediated protein degradation are synergistically linked, off-target toxicity is effectively overcome, and a new strategy is provided for precise treatment of cancers.

Drug combinations of at least one heteroarotinoid and at least one glycolytic inhibitor, which are effective as therapeutic (e.g., anti-cancer treatments), are disclosed. Also disclosed are pharmaceutical compositions and kits containing same, as well as methods of using such drug combinations. Non-limiting examples of heteroarotinoids include SHetA2, SHetA3, SHetA4, SHetC2, SHetD3, SHetD4, SHetD5, SHet50, SHet65, SHet100, OHet72, NHet17, NHet86, NHet90, as well as any combinations thereof. Non-limiting examples of glycolytic inhibitors include 2-deoxy-D-glucose (2-DG); 2-fluoro-2-deoxy-D-glucose (2-FG); 2-chloro-2-deoxy-Dglucose (2-CG); 2-bromo-2-deoxy-D-glucose (2-BG); acetylated derivatives of 2-DG; 3- bromopyruvate (3-BP); 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one) (PFK15); (2E)-3-(3- pyridinyl)-1-(4-pyridinyl)-2-propen-1-one) (3PO); dichloroacetate (DCA); lonidamine (LND); 6- aminonicotinamide (6AN); benitrobenrazide (BNBZ); 1,4,5-oxathiazandioxide-4,4 (GP-2250, misetionamide); (22E,24R)-6β-methoxyergosta-7,9(11),22-triene-3β,5α-diol; and metformin (MET).

The present invention belongs to the technical field of nano-drug formulations, and more specifically, relates to a dual-targeted nano-drug delivery system that combines anti-glutamine metabolism and sensitized photodynamic therapy, its preparation and application. It comprises three components, namely an anti-glutamine metabolism drug, a photosensitizer, and a targeting unit-hydroxyalkyl starch macromolecular conjugate. The anti-glutamine metabolism drug is a derivative of lonidamine, and experiments have proven that it can inhibit glutamine metabolism in tumor cells, thereby reducing the excessive glutathione in tumor stem cells. Moreover, experiments have also shown that the anti-glutamine metabolism drug and the photosensitizer of the present invention can act synergistically to enhance the killing effect of photodynamic therapy on tumor stem cells. By combining anti-glutamine metabolism and photodynamic therapy, the elimination of tumor stem cells is achieved, and the growth and metastasis of tumors are effectively inhibited.

The invention relates to the technical field of metabolism regulators, in particular to a tumor metabolism regulator and a preparation method thereof.The tumor metabolism regulator comprises the combination of two or three active components of 3-bromopyruvic acid, lonidamine and metformin, bromine atoms in the molecular structure of the 3-bromopyruvic acid have the unique electronic effect, and the molecular structure of the 3-bromopyruvic acid has the unique electronic effect; and the binding capacity with metabolic enzyme can be enhanced. The pyruvic acid skeleton can effectively intervene in the end reaction of the glycolysis pathway. As a histamine receptor antagonist, lonidamine not only can regulate the pH value of a tumor microenvironment, but also can regulate and control energy metabolism by influencing a histamine signal channel. Metformin inhibits a mitochondrial complex I and activates an AMPK signal channel, so that multi-level regulation and control on tumor energy metabolism are formed.

The present invention discloses a lonidamine-modified organic compound, and also discloses a cyclometallic complex based on the organic compound, and a preparation method and application thereof. The organic compound of the present invention is obtained by chemically modifying the carboxylic acid group of lonidamine, and has good anti-tumor, antibacterial and anti-inflammatory activities. The cyclometallic complex obtained based on the organic compound can solve the problems of poor lipid solubility and large dosage of lonidamine when it is used as an anti-tumor drug or an anti-tumor drug component, and can also solve the problems of cisplatin tolerance and adverse side effects produced by tumor cells when the simple cyclometallic complex is used as an anti-tumor drug or an anti-tumor drug component. In addition, the cyclometallic complex of the present invention can also be used as a glycolysis inhibitor or an energy metabolism inhibitor to stimulate immune function.

This invention belongs to the field of drug synthesis, specifically relating to a mitochondrial-targeted chlordamine and cinnamaldehyde conjugated prodrug, its preparation method, and its application. The structural formula of the chlordamine and cinnamaldehyde conjugated prodrug is as follows. This invention provides a mitochondrial-targeted chlordamine and cinnamaldehyde conjugated prodrug that, through triphenylphosphine targeting mitochondria, delivers cinnamaldehyde and chlordamine to tumor cells, causing mitochondrial dysfunction and inhibiting tumor cell growth. By introducing various substituents onto the aromatic ring, the spatial conformation of the molecule is improved, enhancing its activity. Chlordamine acts on mitochondria, affecting mitochondrial energy metabolism; through triphenylphosphine targeting tumor cells and synergistic action with cinnamaldehyde, it reduces the side effects of anticancer drugs.

This invention belongs to the field of pharmaceutical technology, and more specifically, relates to a chlordamine derivative targeting tumor mitochondria, its preparation method, and its application. The chlordamine derivative targeting tumor mitochondria provided by this invention has the structure shown in formula (I): wherein R is phenyl, or a phenyl substituted with one or more substituents selected from halogen, C1-C4 alkyl, nitro, and trifluoromethyl. This type of derivative induces oxidative stress in tumor stem cells by targeting mitochondria, disrupting mitochondrial morphology and function, and can induce apoptosis of tumor stem cells at extremely low concentrations. Compared with chlordamine, the mitochondrial-targeting chlordamine derivative has superior anti-tumor growth and metastasis capabilities and can significantly improve the survival time of tumor-bearing mice.

The invention discloses a nanoparticle preparation as well as a preparation method and application thereof. The nanoparticle preparation comprises amino-modified dendritic mesoporous silicon nanoparticles, and lonidamine and oxacillin which are loaded on the mesoporous silicon nanoparticles. According to the invention, lonidamine and oxacillin, which have a synergistic effect, are loaded on the amino-modified dendritic mesoporous silicon spheres, and by means of the electrostatic adsorption effect of amino and bacteria and the degradation effect of mesoporous silicon, the antibacterial drug is slowly released at the infection part, so that a good SCVs killing effect is achieved, and a new treatment strategy is provided for treating SCVs-related osteomyelitis.

The invention discloses a mitochondrial targeted anti-cancer drug based on cyanine and lonidamine and a preparation method and application thereof, and belongs to the technical field of drugs for treating tumors. Cyanine molecules and 3-mercaptobenzoic acid are subjected to a nucleophilic substitution reaction to prepare a cyanine derivative; the preparation method comprises the following steps: carrying out a coupling reaction on a cyanine derivative and a selenocystamine compound to prepare a cyanine-connexon conjugate with an amino terminal; the cyanine-connexon conjugate and lonidamine are subjected to a coupling reaction, and the targeted anti-cancer drug is obtained. According to the mitochondrial targeting anti-cancer drug based on cyanine and lonidamine and the preparation method and application thereof, after the drug targets tumor cell mitochondria, cyanine molecules generate a photodynamic effect and a photothermal effect at the same time under the irradiation of near-infrared light, ROS and high temperature are generated in situ, the mitochondrial structure and function are directly damaged, and the drug can be used for preparing the mitochondrial targeting anti-cancer drug based on cyanine and lonidamine. The ROS also synchronously triggers diselenide bond breakage, lonidamine is accurately released, and mitochondrial dysfunction and metabolic crisis are further aggravated.

The invention relates to a nano preparation and a preparation method and application thereof, in particular to the technical field of biomedical materials. The nano preparation has a core-shell structure and comprises a core and a shell, the core comprises a photosensitizer and a glycometabolism inhibitor, the shell comprises an amphiphilic polymer, the photosensitizer is a near-infrared two-region fluorescent dye TTQ-BT-TPA, the glycometabolism inhibitor comprises lonidamine, the amphiphilic polymer comprises 1, 2, 4-trimethyl-1, 3-pentanediol monoisobutyrate, and the 1, 2, 4-trimethyl-1, 3-pentanediol monoisobutyrate is a near-infrared two-region fluorescent dye TTQ-BT-TPA. The composition is prepared from 1, 2-distearoyl-sn-glycerol-3-phosphoethanolamine-polyethylene glycol 2000 and 2-distearoyl-sn-glycerol-3 The invention provides a nano preparation. In the prior art, a traditional photodynamic therapy is limited in curative effect in a tumor anoxic zone due to dependence on oxygen, and tumor cells maintain a high-level anti-oxidation defense system due to metabolism reprogramming and are insensitive to ferroptosis; and the problem of poor synergistic effect caused by lack of accurate intervention on tumor metabolism and reduction of the yield of fluorescence and active oxygen in a photosensitizer aggregation state of an existing synergistic treatment system is solved.