107 results about "Therapeutic window" patented technology

The present invention relates to the field of medicine, and in particular to a PRMT5 inhibitor, as well as a preparation method therefor and a use thereof. The PRMT5 inhibitor is a compound as shown in formula (I), an enantiomer, a diastereoisomer, a racemate, a solvate, a hydrate, a polymorph, a prodrug, an isotope variant, or a pharmaceutically acceptable salt thereof. The present invention has better activity, selectivity, pharmacokinetic characteristics, safety or a wider treatment window.

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.

Electrically neutral complex compounds of formula I including any stereoisomer or E / Z isomer thereof wherein: M is Fe < 2 + >, Ru < 2 + >, Os < 2 + >, Co < 3 + >, Rh < 2 + >, Rh < 3 + >, Ir < 3 + >, Ni < 2 + >, Pd < 2 + >, Pt < 2 + > or Pt < 4 + >, in particular Ru < 2 + >; t and T'are H or (C1-C3)-alkyl; lig is a bidentate ligand, in particular 2, 2 '-dipyridyl (bpy) or 4, 7-diphenyl-1, 10-phenanthroline (BPhen); and A is an anion from a pharmaceutically acceptable acid, the electrically neutral complex compounds of formula I are useful in human therapy, in particular as photosensitizers (PS) in photodynamic therapy (PDT) of cancer, skin diseases, fungal infections or microbial infections. They are almost non-toxic under dark conditions at therapeutic doses and exhibit good to excellent photoactivity under hypoxic conditions. They can be used for PDT treatment of deep hypoxia tumors by using light within a far-infrared to near-infrared light treatment window.

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 provides compositions comprising a single protein having one or more molecules of a pharmaceutical agent tightly bound therein. The compositions are useful to decrease the toxicity and / or to widen the therapeutic window of the pharmaceutical agent. The invention also provides methods for preparing such a composition.

The present invention discloses an antibody-drug conjugate and a preparation method and application thereof, in particular, a conjugate of an anti-PD-L1 antibody and a TLR7 and / or TLR8 agonist and a pharmaceutical composition, preparation method and application thereof. The present invention obtains a modified anti-PD-L1 antibody with a mutant cysteine ​​by gene editing, which basically retains the structure of the original antibody and can be used for the construction of an antibody-drug conjugate. Through anti-tumor experiments, it was found that the obtained antibody-drug conjugate has better activity, such as strong anti-tumor activity, can significantly improve the survival rate of tumor-bearing animals, and has significantly reduced toxicity, less burden on the body of experimental animals, greatly reduces the minimum effective dose of small molecule drugs when used alone, expands its therapeutic window, and is expected to be used in the development of therapeutic drugs for various diseases (such as tumors, viral diseases such as hepatitis B, etc.), with good application prospects and value.

Disclosed in the present invention are an antigen binding protein targeting CD40, and the preparation therefor and the use thereof. The antigen binding protein targeting CD40 has the characteristics of a high affinity to CD40 and a strong agonistic activity on signaling pathways, particularly the enhanced agonistic activity after crosslinking, so that the antigen binding protein targeting CD40 has a larger therapeutic window, and is expected to bring about new opportunities for the treatment of various tumors.

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 concerns homogenous antibody-oligonucleotide conjugates (AOCs) having structure (1): Ab–[ (Z)y1 – LD – (D)x ]z (1), wherein Ab is an antibody, Z is a connecting group obtainable by reaction between two click probes, x is 1, 2, 3 or 4, y1 is 1 or 2, z is 2 or 4, LD is an heterobifunctional (x + y1)- valent linker; and D is an oligonucleotide. The AOCs are homogenous, readily prepared, and effective in targeted delivery of the oligonucleotide to a cell of interest with high efficacy. The AOCs according to the invention have an improved therapeutic window and improved efficacy over conventional AOCs. Hence, the AOCs are effective in the treatment of disorders like muscular dystrophy. In a first aspect, the invention concerns the use of novel linkers for the efficient preparation of AOCs. In a second aspect, the invention concerns the medical use of AOCs for the treatment of neuromuscular disorders. In a third aspect, the invention concerns specific AOCs that are particularly suitable in treatment. In a fourth aspect, the invention concerns the use of ultrafast click chemistry in the preparation of AOCs.

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 present invention is concerned with dose regimens for administering the glutaminyl cyclase inhibitor varoglutamstat, and pharmaceutical compositions containing the same, to a subject, providing an optimized therapeutic window for therapeutic uses thereof and methods of treatment employing them.

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 relates to the field of biotechnology, and specifically discloses a recombinant protein for improving the efficacy of ADC drugs and its application. The recombinant protein includes a tumor cell surface targeting structure, a cell-penetrating structure, and a toxin molecule; the toxin molecule is linked and fused with the tumor cell surface targeting structure and / or the cell-penetrating structure; the tumor cell surface targeting structure is a protein structure capable of specifically binding to a target on the surface of tumor cells; the cell-penetrating structure is a protein structure that mediates the penetration of the recombinant protein through the cell membrane into the cell interior. This application uses the tumor cell surface targeting structure to specifically recognize the target on the surface of target cells and exert the killing activity of conventional antibodies, and then brings the toxin molecule into the tumor cells through the cell-penetrating structure, and the toxin is released to play a role in killing tumors, improving the efficacy of ADC drugs. Among them, the cell-penetrating efficiency of the cell-penetrating structure in this application can be increased to 50-90%, thereby improving the therapeutic window of traditional ADC drugs.

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 application discloses a nucleic acid aptamer of maytansine and application thereof, the nucleic acid aptamer is Seq2-X, and a DNA sequence of Seq2-X is shown as SEQ ID NO. 1. The nucleic acid aptamer can be combined with the target maytansine with high affinity and high specificity, the equilibrium dissociation constant is in the nanomolar range, the water solubility is good, and after being combined with the fat-soluble maytansine, the solubility of the drug can be improved. By utilizing the specific interaction between the nucleic acid aptamer and maytansine, the stability of maytansine drug can be improved, the cytotoxicity of maytansine is enhanced, and the treatment window is widened. By utilizing the nucleic acid aptamer as a drug delivery carrier of maytansine, the limitation of maytansine in clinical application can be improved, which has important significance for the design and development of maytansine drugs in clinical application.

The present invention relates to bifunctional fusion molecules comprising a mutated polypeptide ligand (e.g., mutated IFN-α) having reduced biological activity attached to a disease tissue targeting biologic or a tumor associated antigen (TAA)-targeting biologic (e.g., anti-PD-L1 antibody), wherein the targeting biologic or TAA-targeting biologic directs the mutated ligands to cells that express on their surfaces the antigens to which said targeting biologic binds, as well as receptors for said ligands. Importantly, because the mutated polypeptide ligands have reduced biological activity, the resultant fusion molecule have reduced off-target activity / toxicity. More importantly, the targeting of the mutated ligand by the targeting biologic restores the activity of the mutated ligand, with the degree of activity restoration apparently correlated with the level of targeting biologic on the cells. As such, the fusion molecules of the present invention advance the state of art by providing bifunctional fusion molecules having a greater therapeutic window than those previously described. The invention further relates to methods of treating cancer in a patient and in particular, patients with refractory and / or recurrent cancers involving the use of these bifunctional fusion molecules. The invention also relates to methods of treating infectious disease, including but not limited to chronic hepatitis B and C infections in a patient involving the use of these bifunctional fusion molecules.

The invention relates to saRNA (Ribonucleic Acid) and application thereof, a saRNA vaccine, a method and a pharmaceutical composition, the saRNA for coding HSV (Herpes Saturation Virus) ICP34.5 is constructed, the translation and expression capability of a gene can be obviously enhanced, the use of the saRNA in a gene delivery system is optimized, a more excellent application carrier is provided for vaccine and gene therapy, the antiviral innate immune response of a host can be inhibited by coding ICP34.5 and saRNA, and the anti-virus innate immune response of the host can be inhibited by coding ICP34.5 and saRNA. According to the present invention, the expression and the translation of the gene are enhanced by inhibiting PKR and IFN signal channels, particularly by inhibiting PKR and IFN signal channels and reducing translation closure, the addition of the ICP34.5 is beneficial to prolonging the expression time of the gene of interest and providing the lasting treatment effect, and the integration of the ICP34.5 ensures the same immune escape characteristic of the offspring saRNA, optimizes the gene delivery system, and improves the efficiency and the effect of the offspring saRNA. By coding ICP34.5 and saRNA, strong innate immune response can be reduced, side effects in gene therapy can be reduced, and a therapeutic window can be improved.

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 provides compositions comprising a single protein having one or more molecules of a pharmaceutical agent tightly bound therein. The compositions are useful to decrease the toxicity and / or to widen the therapeutic window of the pharmaceutical agent. The invention also provides methods for preparing such a composition.

The disclosure relates to novel saponins comprising acetyl residues on two of their sugar residues. These saponins are able to enhance the transfection efficiency to a high extent and show much less cytotoxic side effects than already known saponins.

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 application relates to the technical field of medicines, and in particular to an eribulin derivative and an antibody-drug conjugate (ADC) thereof, and a medical use thereof. In the present application, a series of derivatives with good tumor suppression effects are synthesized by modifying eribulin, and have lower toxicity and a larger therapeutic window than that of eribulin; and then the the eribulin derivative and an antibody are made into an ADC by means of an appropriate linker, and the therapeutic efficiency of the eribulin derivative is improved using the targeting specificity of the antibody.

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.