68 results about "Therapeutic window" patented technology

The present invention relates to a saponin-based saponin derivative comprising a triterpene aglycone and a first and / or second sugar chain, the saponin derivative comprising: an aglycone core structure containing a derivatized aldehyde group; and / or the first sugar chain containing a derivatized carboxyl group; and / or the second sugar chain containing at least one derivatized acetoxy group. The present invention also relates to a first pharmaceutical composition comprising the saponin derivative of the present invention. In addition, the present invention relates to a pharmaceutical combination comprising the first pharmaceutical composition of the present invention and a second pharmaceutical composition comprising any one or more of an antibody-toxin conjugate, a receptor-ligand-toxin conjugate, an antibody-drug conjugate, a receptor-ligand-drug conjugate, an antibody-oligonucleotide conjugate, or a receptor-ligand-oligonucleotide conjugate. The present invention also relates to the first pharmaceutical composition or the pharmaceutical combination of the present invention for use as a medicament or in the treatment or prevention of cancer, an infectious disease, a viral infection, hypercholesterolemia, primary hyperoxaluria, hemophilia A, hemophilia B, alpha-1 antitrypsin-associated liver disease, acute hepatic porphyria, transthyretin-mediated amyloidosis, or an autoimmune disease. Furthermore, the present invention relates to an in vitro or ex vivo method for translocating a molecule from outside a cell into the cell, which method comprises contacting the cell with the molecule and with a saponin derivative of the present invention.

The invention relates to the technical field of biological medicine, in particular to application of hordenine in preparation of a lysosome targeting preparation. The hordenine can be captured by the lysosome and accumulated in the lysosome, so that the hordenine has the characteristic of targeting the lysosome, and the hordenine can be used for preparing the lysosome targeting preparation. Hordenine is small in toxic and side effects and high in safety, and the problems that existing lysosomal targeted compounds such as chloroquine are high in toxicity and narrow in therapeutic window are effectively solved.

The invention discloses a precise control device for continuous infusion of a boron-loaded drug, which overcomes the defects of insufficient precise control, poor continuity and no dynamic closed loop in the existing boron neutron capture therapy. The device comprises a first shell and a second shell which are connected through a hinge, the device is further provided with an electromagnetic drive extrusion assembly, a fixing assembly and a rope ring, and the electromagnetic drive extrusion assembly comprises an electromagnet, a magnetic conductive block and a first elastic piece. The device further comprises a module which is specifically a data collecting and processing module and can collect liquid medicine parameters, pipeline parameters, physiological parameters and flow velocity data and remove abnormal data through filtering processing. And the influence factor calculation module can calculate a physiological state influence factor and an infusion resistance influence factor. Through electromagnetic pressure control, multi-factor calibration and multi-patient overall planning, the flow velocity precision meets the precision infusion requirement, the effective concentration of boron-loaded medicine in the body is stabilized in a treatment window, and the infusion interruption risk is greatly reduced.

The utility model belongs to the technical field of medical instruments, and discloses a treatment head and a therapeutic apparatus, the treatment head comprises a body and a light emitting member, the body is provided with a treatment end used for contacting skin, and the treatment end is provided with a treatment window; the light-emitting part is arranged in the body and used for emitting light outwards from the treatment window. Or, the light-emitting part is arranged at the treatment end and used for emitting light in the direction away from the treatment end; the light-emitting part is used for detecting whether the treatment end is well attached to the skin or not, and when the treatment end is well attached to the skin, light emitted by the light-emitting part does not leak. The accuracy of fitting degree detection between the treatment head and the treatment area is improved, the operation is simple, and immediate adjustment can be carried out to ensure the treatment effect.

This application provides isolated antibodies, and antigen-binding fragments thereof, that specifically bind endothelin A receptor (ETAR). These ETAR antibodies, or antigen-binding fragments thereof, have a high affinity for ETAR, function to effectively block ET-1 binding to ETAR, are less immunogenic compared to their unmodified parent antibodies in a given species (e.g., in a human), and can be used to treat ETAR-associated disorders. Importantly, compared to small molecule ETAR antagonists, the antibodies of the present invention have advantages of longer serum half-life, higher target specificity, thereby limiting the risk of off-target toxicity and improving therapeutic window.

The invention relates to the technical field of medicaments, in particular to an astragalus polysaccharide selenium compound capable of regulating tumor microenvironment and preparation thereof, and the astragalus polysaccharide selenium compound comprises the following components in parts by weight: modified nano GABA (gamma-aminobutyric acid) particles, spina date seed flavone extract, xylaria nigripes polysaccharide, N-acetylcysteine modified chitosan, vitamin B6, a trehalose stabilizer and natural menthol. According to the invention, the synergistic effect of stability improvement, delivery efficiency optimization and efficacy synergistic enhancement is formed through cooperation of the components instead of simple superposition of the components. Due to the slow release characteristic of the modified nano GABA particles, the concentration of GABA in a central nervous system is maintained within an effective therapeutic window, and a time window is provided for the synergistic effect of the spina date seed flavone extract and xylaria nigripes polysaccharide; the flavone extract inhibits the release of excitatory transmitters and reduces the action load of GABA (gamma-aminobutyric acid), so that a small amount of GABA can achieve an ideal regulation effect; the xylaria nigripes polysaccharide improves the sensitivity of nerve cells to GABA (gamma-aminobutyric acid), which is equivalent to the effect of amplifying the GABA.

The invention discloses a tumor treatment synergistic interaction system and method based on the acoustic cavitation effect of a phase-change nano-droplet. The system comprises the phase-change nano-droplet entrapped with a chemotherapeutic drug and a sound-sensitive agent and a cavitation effect intelligent monitoring and adjusting system. The method is characterized in that cavitation noise signals of a tumor target area are collected in real time through a cavitation monitoring system integrated in an ultrasonic probe, the inertial cavitation dosage is rapidly calculated through a signal processing system and compared with a preset threshold value, then a feedback instruction is generated to dynamically regulate and control ultrasonic irradiation parameters, and intelligent closed-loop control is formed. According to the method, the cavitation effect can be accurately maintained in an ideal treatment window, targeted release and deep penetration of the medicine and activation of the sound-sensitive agent are synchronously achieved through cavitation mechanical energy, and time-space synchronous synergistic interaction of chemotherapy and sonodynamic therapy is achieved.

The invention relates to application of a ZNF621 protein activator in preparation of drugs, and belongs to the technical field of biological medicines. The invention provides application of a ZNF621 protein activator in preparation of drugs, the ZNF621 protein activator is at least one of natural fatty acid compounds FA4, FA89 and FA95 and derivatives thereof, and the drugs are used for treating or inhibiting lipid metabolism disorder diseases or treating malignant tumors. The natural fatty acid compound and the derivative thereof are high in targeting property, clear in action mechanism, remarkable in treatment effect, wide in treatment window, lasting in action and low in cost.

A pharmaceutically acceptable salt of a polypeptide and a use thereof. According to the pharmaceutically acceptable salt of the polypeptide, the half-life of a drug is prolonged by means of a study on the structure-activity relationship and structural modification, the in-vivo exposure is increased, the number of times of administration is reduced, the side effect in animal experiments is lower, and the therapeutic window of the drug is larger. The pharmaceutically acceptable salt of the polypeptide can be used for treatment of ETBR receptor-related diseases, such as rehabilitation treatment of the acute phase and the recovery phase of a cerebral arterial thrombosis patient, promoting better recovery of the stroke patient.

The invention relates to a ligand drug conjugate with a free load recovery unit and an application of the ligand drug conjugate in prevention or treatment of diseases, the ligand drug conjugate can remove free loads through the connected recovery unit capable of being combined with the free loads, the medication safety is remarkably improved, and the application range of the ligand drug conjugate is widened. Meanwhile, the load carried by the ligand drug conjugate can be increased on the whole by recovering the free load, and the activity loss caused by load falling is made up. Therefore, by introducing the recovery unit, the recovery of the free load is realized, the safety and effectiveness of the ligand-coupled drug can be remarkably improved, and the therapeutic window is expanded.

This invention discloses a FA-ICG-NBs nanobubble, its preparation method, and its application in the preparation of tumor-targeted therapeutic agents. The FA-ICG-NBs nanobubble employs a composite phospholipid shell, with folic acid (FA) covalently bonded to the surface and indocyanine green (ICG) loaded onto it, encapsulating a mixture of oxygen and sulfur hexafluoride. The preparation method includes: preparing a lipid solution for forming the composite phospholipid shell; mixing the lipid solution with the oxygen and sulfur hexafluoride mixture, and then performing a reciprocating shearing gas-liquid interface self-assembly to obtain the FA-ICG-NBs nanobubble. The FA-ICG-NBs nanobubble prepared by this invention utilizes dual-wavelength photoacoustic imaging for non-invasive assessment of tumor blood oxygenation and hypoxia improvement, combined with ICG fluorescence timing for screening the optimal therapeutic window, and synergistic oxygen-enhanced sonodynamic therapy. It exhibits good biocompatibility, structural stability, and integrates targeted enrichment, blood oxygenation assessment, hypoxia monitoring, timing regulation, and enhanced therapeutic effects.

The invention discloses a compound for targeted enhancement of a transcription function of p53 protein and application of the compound. The compound TETACs not only can stabilize a p53 Y220C mutant protein, but also can actively recruit a transcription co-activator to a p53 target gene promoter region and specifically enhance the transcription function of p53, so that the cycle arrest and apoptosis of tumor cells are intensively induced, the tumor growth is effectively inhibited, and the compound TETACs has inhibitory activity on various tumor cells; in addition, as a heterobifunctional molecule, the TETACs play a role in a catalytic and substoichiometric manner, and have a more lasting curative effect and a wider therapeutic window.

The invention belongs to the technical field of medical ultrasonic remote monitoring, and discloses an echocardiogram remote monitoring system for a heart failure patient, which can capture acute cardiac function deterioration corresponding to paroxysmal dyspnea and postural chest distress at night in real time through a symptom pre-recognition module, an emergency level data transmission mechanism and continuous cardiac function parameter calculation; the system no longer only transmits static images, but generates a continuous cardiac function dynamic curve, and combines a causal reasoning algorithm to help doctors to clearly distinguish physiological and pathological attributes of parameter fluctuation, so that intervention delay caused by monitoring lag is avoided, a precious treatment window is won for acute cardiac function deterioration, and the risk of acute exacerbation of heart failure is reduced; based on the integrated data, the causal reasoning algorithm can quickly locate the heart failure deterioration pathogenesis, such as association between EF value decrease and anemia and renal injury, a physician does not need to manually integrate data across platforms, the time consumed for pathogenesis investigation is reduced, timely adjustment of a treatment scheme is ensured, and blind medication caused by unknown pathogenesis is avoided.

The present disclosure provides a novel panel of fully humanized bispecific ADCs targeting CDH17 and another clinically validated target such as EGFR and HER2 for gastrointestinal cancers treatment. The bispecific ADCs offer improved target coverage, internalization rate and cytotoxicity over parental antibodies, as well as safety profile for a wider therapeutic window.

Provided are a tetrodotoxin conjugate, a method for preparing same, and use thereof. A carboxyl-containing macromolecular compound and tetrodotoxin are used as the starting materials, and after a catalyst and a solvent are added, the tetrodotoxin conjugate is obtained by means of a coupling reaction. The carboxyl-containing macromolecular compound is selected from carboxylated dextran, carboxylated β-cyclodextrin, alginic acid, and polyacrylic acid. The tetrodotoxin conjugate can be used in the preparation of a sodium channel blocker and a medicament for treating neuropathic pain caused by chemotherapy, and possesses an analgesic effect associated with tetrodotoxin (TTX). In addition, the therapeutic window is increased, thereby greatly improving the safety.

The invention relates to a therapeutic combination, comprising a first proteinaceous molecule comprising a first binding site for binding to a first epitope of a first cell-surface molecule, the first proteinaceous molecule provided with at least one saponin covalently bound to an amino-acid residue of said first proteinaceous molecule, and comprising a second pharmaceutical composition comprising a second proteinaceous molecule different from the first proteinaceous molecule, the second proteinaceous molecule comprising a second binding site for binding to a second epitope of a second cell-surface molecule different from the first cell-surface molecule, and comprising an effector moiety, wherein the second epitope is different from the first epitope. An aspect of the invention is a composition comprising the first proteinaceous molecule and the second proteinaceous molecule of the invention. The invention also relates to a composition or therapeutic combination comprising an antibody—drug conjugate or antibody—oligonucleotide conjugate and the first proteinaceous molecule of the invention. An aspect of the invention relates to a pharmaceutical composition comprising the composition or the antibody—drug conjugate of the invention, and optionally further comprising a pharmaceutically acceptable excipient. The invention also relates to the therapeutic combination or the composition or the antibody—drug conjugate or the pharmaceutical composition of the invention, for use as a medicament. The invention also relates to the therapeutic combination of the invention for use in the treatment or prophylaxis of a cancer.

The invention relates to a lymphatic tissue targeted composite nanocluster as well as a preparation method and application thereof. The composite nanocluster comprises Se-doped ZnS nanoparticles and BSA (Bovine Serum Albumin) coated on the surfaces of the nanoparticles. The nano platform for synergistically targeting lymphatic tissues integrates the complementary immunoregulation functions of zinc and selenium, overcomes the curative effect limitation of a single element through the synergistic effect of elements, and widens the safe treatment window of necessary trace elements; the natural lymph targeting characteristic of the serum albumin is utilized to realize efficient lymph node delivery of the nanocluster; meanwhile, the nano-cluster structure can promote in-vivo removal, so that long-term accumulation is reduced, and the safety is ensured.

The application discloses a kind of self-adjusting laser power control method and system based on temperature prediction, belong to medical equipment intelligent control technical field.Through constructing a forward-looking adaptive control closed loop: system first real-time continuous acquisition and constructs the temperature sequence of target area;Using pre-trained time series prediction model, based on current and historical temperature and power data, predict the temperature change trend in future short term;When it is predicted that temperature will deviate from the preset safe and effective treatment window, calculate and output smooth laser power regulation instruction in advance, drive actuator to actively intervene.The application can dynamically compensate biological tissue thermal inertia and environmental disturbance, maintain the temperature of treatment area in the preset target range with high precision and high stability, significantly improve the safety and controllability of treatment, and provide a key intelligent control solution for the clinical transformation of photothermal therapy.

The invention belongs to the technical field of medicines, and particularly relates to an aryl alkyl azole derivative as well as a preparation method and application thereof. Benzo [d] [1, 3] thiazine is used as aryl and is directly connected with 4H-1, 2, 4-triazole-4-yl through a chemical bond, and alkoxy is introduced to the C6 position of the aryl, so that the aryl alkyl azole derivative is obtained. The compound disclosed by the invention is novel in structure, shows excellent anti-convulsion activity in two epilepsy models of maximum electroshock and subcutaneous pentyltetrazole as a GABAA receptor agonist, and particularly shows an extremely high protection index, PIgt, in the subcutaneous pentyltetrazole model; and 10, the compound has the remarkable advantages of various action mechanisms, wide therapeutic window and low neurotoxicity, can be used for preparing the anti-epilepsy medicine, and is particularly suitable for treating intractable epilepsy.

This invention relates to the field of special medical foods, and particularly to a special medical food formula for colorectal cancer patients, its preparation method, and its application. The raw materials, in parts by weight, include: 20-30 parts Codonopsis pilosula, 20-30 parts Rehmannia glutinosa (processed), 20-30 parts Astragalus membranaceus, 10-20 parts Coix lacryma-jobi (raw), 10-20 parts Atractylodes macrocephala, 10-20 parts Poria cocos, 10-20 parts Angelica sinensis, 10-20 parts Paeonia lactiflora, 10-20 parts Prunus persica, 3-6 jujubes, 3-15 parts Glycyrrhiza uralensis, 6-15 parts phycocyanin, and 6-15 parts citric acid. This formula can have anti-tumor effects, reduce the toxic side effects of chemotherapy, enhance the reticuloendothelial cell system, promote the enhancement of specific and non-specific immune functions in the body, thereby reducing tumor volume and inhibiting tumor proliferation and metastasis. The drug is encapsulated in Dunaliella salina exosomes and targeted modified to ensure accurate delivery to the lesion site, increasing bioavailability and reducing the drawbacks of a small therapeutic window and high toxicity.

The invention discloses a preparation method of alpha-ketoisovaleric acid in an anti-hepatic fibrosis drug, and relates to the technical field of hepatic fibrosis treatment drug development, and the preparation method comprises the following steps: mixing alpha-ketoisovaleric acid with pharmaceutic adjuvants to prepare a pharmaceutically acceptable dosage form; the dosage of the alpha-ketoisovaleric acid is determined based on the pharmacological activity of the alpha-ketoisovaleric acid in the concentration range of 50 mu M to 200 mu M, wherein the alpha-ketoisovaleric acid can inhibit hepatic stellate cell activation induced by a transforming growth factor-beta; an endogenous metabolite alpha-ketoisovaleric acid is applied to preparation of an anti-hepatic fibrosis medicine, and based on the pharmacological activity of the alpha-ketoisovaleric acid for specifically inhibiting activation of TGF-beta induced hepatic stellate cells at the concentration of 50-200 mu M, a novel anti-hepatic fibrosis preparation which is high in safety, wide in therapeutic window and free of liver and kidney accumulation risk is developed. The medicine is not only suitable for treating hepatic fibrosis caused by various causes such as non-alcoholic fatty liver disease, viral hepatitis, alcoholic liver disease and drug-induced liver injury, but also meets the requirements of early intervention and severe treatment through reasonable dosage form design and administration route selection.

Methods and circuitry for calibrating stimulation circuitry in an implantable stimulator device (ISD) is disclosed. The ISD can sense neural response to the stimulation, and use an algorithm to assess those responses and determine a therapeutic window for a particular stimulation parameter, such as amplitude. Stimulation circuitry in the ISD is programmed with information indicative of the determined therapeutic window, such as by programming a minimum and / or maximum current amplitude. As well as restricting operation of the stimulation circuitry to within the therapeutic amplitude window, such programming calibrates the stimulation circuitry and allows an expanded range of, or all of, amplitude values supported by the stimulation circuitry to be used, which allows the amplitude to be incremented in smaller current increments.

The invention discloses a compound or pharmaceutically acceptable salt thereof as well as a preparation method and application thereof. The invention further discloses 22 compounds of the type and a chemical synthesis method thereof, the synthesis route is simple, operation and implementation are easy, and needed reagents are easy to purchase. The novel DIQ01 and the derivative thereof found in the invention can be specifically combined with a target protein KHSRP and inhibit the function of the target protein KHSRP, and the structure type is novel; compared with a plurality of clinical drugs, the compound shows better tumor anti-proliferation activity, and has good tumor selectivity and a wide treatment window. The compound and the pharmaceutical composition thereof can be used for preparing medicines for treating various tumors, and are preferably used for preventing or treating solid tumors such as colorectal cancer, breast cancer, lung cancer and the like and hematological malignant tumors.

The invention relates to an application of 7-phenylcarbamoyl heptanoic acid in preparation of antitumor drugs, in particular to a new application of 7-phenylcarbamoyl heptanoic acid in preparation of antitumor drugs, which develops the medicinal value of 7-phenylcarbamoyl heptanoic acid and has high antitumor activity on solid tumors or hematologic tumors. In-vivo experiments show that under an effective dose, the 7-phenylcarbamoyl heptanoic acid does not cause obvious weight loss, weight change of main organs or histopathologic injury of experimental animals, so that the 7-phenylcarbamoyl heptanoic acid has a relatively good treatment window and good safety.

This invention relates to the field of pharmaceutical technology, specifically to a 6-(6-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)quinazoline-4-amine derivative, its preparation method, and its applications. This invention utilizes a "conformation-locking" and "drug-likeness optimization" strategy to optimize the 4-position side chain of quinazoline into conformationally defined structures such as dihydroindanol and fluoropiperidine, thereby reducing P-gp recognition through conformational rigidity. Simultaneously, the introduction of groups such as cyclopropylformyl groups reduces off-target toxicity, thus broadening the therapeutic window. The 6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazoline-4-amine derivative provided by this invention simultaneously achieves potent DYRK1A inhibition, high kinase selectivity, low microglial cytotoxicity, significant anti-neuroinflammatory effects, good blood-brain barrier permeability, and oral bioavailability. Furthermore, it is a novel small-molecule inhibitor that can be validated for cognitive improvement in AD animal models, possessing significant clinical value and urgent application needs.

The invention discloses a theophylline alkaloid salt, a pharmaceutical composition thereof, a preparation method of the theophylline alkaloid salt, and an application of the theophylline alkaloid salt, and belongs to the technical field of pharmaceutical chemistry. Natural alkaloids with definite pharmacological activity, such as stachydrine, betaine, trigonelline, sophocarpidine, choline or berberine, are selected as saline-forming bases, and a series of novel theophylline alkaloid salts are developed. The functional salt formation strategy not only fundamentally changes the traditional theophylline salt formation mode, but also realizes a leap-through breakthrough from single improvement of solubility to synergistic interaction and active attenuation. Through inherent gastric mucosa protection, heart function regulation and other effects of alkaloid, an active attenuation mechanism is constructed, the core toxic and side effects of gastrointestinal irritation, heart excitability and the like caused by theophylline are effectively reduced, the risk of introduction of exogenous sensitizers is avoided, and the bioavailability of theophylline is improved. The clinical problems of narrow therapeutic window and large toxic and side effects of traditional theophylline and salt drugs thereof are effectively solved.

The invention discloses application of 3-hydroxyglutaric acid in preparation of a medicine for preventing and / or treating hyperuricemia related diseases and the prevention and treatment medicine. The activity of 3-hydroxyglutaric acid capable of reducing the uric acid level in the body is found and confirmed for the first time, and the 3-hydroxyglutaric acid is pioneering discovery of new application of known substances; through rigorous dose effect relationship research, a'treatment window 'which is lower than a toxicity threshold value and can effectively reduce uric acid is determined. As an endogenous metabolic intermediate of a human body, the biocompatibility under low dosage is expected to be superior to that of a chemically synthesized medicine, and the potential side effect risk after long-term use is lower.

This invention discloses an antitumor compound, its preparation method, and its application, relating to the field of antitumor compound technology; it has the structure described in general formula I; the antitumor compound provided by this invention has good antitumor activity, and while maintaining highly efficient killing activity against tumor cells, its toxicity to normal cells is significantly reduced, resulting in a wider therapeutic window and potential clinical safety advantages.

Disclosed is a system and method for a non-oral dopaminergic therapy for patients with Parkinson's disease, the administration thereof having the benefit of no change in risk to the patient. The disclosed therapy is capable of delivering prescribed doses of carbidopa / levodopa through the skin into the bloodstream where it may circulate systemically in the body, bypassing the digestive system and avoiding first-pass metabolism in the liver. The dislosed drug delivery system enables therapeutic dosages of carbidopa / levodopa to reach the target tissue site in a controlled manner while maintaining the concentration in the therapeutic window.