67 results about "Reduced toxicity" patented technology

The invention discloses an ROS-responsive prostate cancer targeting prodrug as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The prodrug is formed by covalently linking a prostate cancer targeting peptide SYEELR, a ROS (reactive oxygen species) response type ketal thiol (TK) connexon and an active molecule Devimistat. The preparation method comprises the following two steps: firstly, coupling Devimistat with a TK linker to obtain an intermediate Dev-TK, and then coupling the intermediate Dev-TK with an SYEELR peptide fragment to obtain a target product. The prodrug can specifically break and release Devimistat in a tumor high active oxygen microenvironment, and active targeting delivery is realized by virtue of the SYEELR peptide. The invention provides a novel prostatic cancer treatment strategy with accurate targeting, controllable release, enhanced curative effect and toxicity reduction potential.

The invention provides a relieving and sunscreen plant composition with effects of reducing toxicity and enhancing efficacy as well as a preparation method and application thereof, and belongs to the technical field of medicines. The composition is prepared from the following raw materials in parts by weight: 5 to 8 parts of water-containing inula flower extract, 10 to 15 parts of chamomile extract, 4 to 6 parts of radix gentianae extract and 25 to 40 parts of schizophyllan. The composition is prepared through precise combination and scientific process treatment of the four active ingredients, the relieving effect on skin injuries caused by sun-screening agent stimulation and ultraviolet radiation is remarkably improved, the resisting effect of ultraviolet light on the skin injuries is remarkably improved, part of chemical sun-screening agents can be replaced, the toxicity of cosmetics is reduced, and the skin care effect is good. The synergistic effect of toxicity reduction, efficient ultraviolet resistance and soothing and repairing is achieved, and a new technical scheme is provided for developing cosmetics with low toxicity, efficient ultraviolet resistance and sunscreen two-way soothing and repairing.

This invention provides a non-cytotoxic, in vivo compatible proximity labeling method for peroxidases, Hi-APEX, and its applications, belonging to the field of biotechnology. This invention provides a method for labeling interacting proteins, neighboring proteins, and / or neighboring RNA. By introducing TP probes, it completely overcomes the core limitation of peroxidase dependence on H2O2 without sacrificing the original high spatiotemporal resolution. The method provided by this invention exhibits significantly superior technical effects compared to existing technologies in terms of reduced toxicity, enabling in vivo application, precise analysis of redox-sensitive processes, dynamic tracking of protein transport, and simultaneous spatial multi-omics analysis. It provides a powerful tool for life science research and drug development, possessing significant scientific value and broad application prospects.

Provided are intermittent administration methods for reducing toxicity in the treatment of conditions associated with increased 15-hydroxyprostaglandin dehydrogenase (15-PGDH) activity or expression levels in a subject with a 15-PGDH inhibitor. Further, provided herein are methods of treating a condition associated with increased 15-hydroxyprostaglandin dehydrogenase (15-PGDH) activity or expression level in a subject by administering a 15-PGDH inhibitor while maintaining the therapeutic effect of the 15-PGDH inhibitor when the plasma concentration of the 15-PGDH inhibitor in the subject drops below the EC50 of the 15-PGDH inhibitor.

The invention discloses an application of a T cell subset in improving the treatment effect of AK112. The T cell subset is XCL1 + CCL3 + CD8 + T cells. The invention relates to an application of a specific T cell subset in improving the curative effect of AK112, a T cell agonist and AK112 are combined for use, and by synergistically activating the T cell function and reversing the immunosuppression microenvironment, the single drug resistance of AK112 is effectively overcome, the continuous remission time is remarkably prolonged, the treatment response is deepened, the applicable patient group is expanded, and meanwhile, the toxicity risk is reduced. The invention further develops a full-spectrum flow cytometry kit containing 13 antibodies, 13 key markers of the T cell subgroup can be simultaneously detected by one tube, patients sensitive to evoximab treatment (i.e., high expression of the subgroup) can be efficiently screened out, and a convenient tool is provided for accurate medication.

The present disclosure relates to a novel platform for the design of multi-specific antibodies, incorporating innovative splits of antibodies, cytokines, or other proteins at various positions within a single antibody framework. This design aims to reduce toxicity and enhance therapeutic efficacy, particularly in applications such as immunotherapy and antibody-drug conjugates (ADCs). Multi-specific antibodies—including monospecific, bispecific, and multi-specific forms—comprise one or more antigen-binding domains that engage one or more epitopes of the same or different antigens. This disclosure encompasses methods for producing antibodies with one, two, or multi antigen-binding domains, which may consist of immunoglobulin heavy chain variable domains alone or in combination with other functional domains.

The invention relates to the technical field of radiopharmaceutical research and development, and discloses a radiotargeted nuclide drug molecule design method based on a first principle, comprising: screening a high-specificity target based on a preset demand, and screening candidate nuclides according to drug functions and ligand types corresponding to the high-specificity target; the method comprises the following steps: setting a difunctional chelating agent adaptive to candidate nuclides, setting a ligand for a high-specificity target, setting a linker for connecting the difunctional chelating agent and the ligand, calculating and optimizing the difunctional chelating agent, the ligand and the linker according to a first principle, and assembling according to a nuclide-chelating agent-linker-ligand sequence to obtain an initial molecular complex; and for alpha nuclide in the initial molecular complex, calculating and optimizing through a first principle to obtain a target molecular complex. According to the method, by constructing collaborative design logic, the drug targeting property, stability and the balance capacity of the curative effect and safety are improved, special optimization is carried out for alpha nuclide risks so as to reduce toxicity, and extensive expandability is achieved.

The present disclosure provides cyclodextrin inclusion complexes of a β-cyclodextrin substituted host molecule wherein the guest is tirapazamine. The molar ratio of the tirapazamine guest to the cyclodextrin host ranges from about 14:1 to about 2:1, inclusive. The complexed tirapazamine has advantageous properties when compared to non-complexed tirapazamine in that the tirapazamine complex is water soluble and, at a molar ratio of the β-cyclodextrin substituted host molecule to the tirapazamine guest of 2:1, the pH of a 0.7-1 mg / mL solution of the inclusion complexes containing tirapazamine ranges from about pH 5.3 to about pH 6.4. The present disclosure also provides pharmaceutical compositions comprising a pharmaceutically acceptable carrier and cyclodextrin inclusion complexes of β-cyclodextrin substituted host molecules wherein the guest is tirapazamine. The pharmaceutical composition comprising the β-cyclodextrin-complexed tirapazamine demonstrates improved stability, improved solubility and reduced toxicity of the tirapazamine compared to non-complexed tirapazamine alone.

The application relates to the field of medicine, in particular to a ROS (reactive oxygen species)-responsive liposome containing kaempferol and a preparation method and application thereof, to solve the problems of poor kaempferol efficacy and how to reduce the toxicity of PFOB in the prior art, realize stable kaempferol drug release, and improve the bioavailability. The liposome is a ROS-responsive liposome containing kaempferol, the liposome is a DTP liposome, the DTP liposome is a double-layered inner and outer layer with distearoyl phosphatidyl ethanolamine-polyethylene glycol as the outer shell of the liposome, a ketone thioacetal bond is located between the outer shells of the liposome, the drug loaded in the DTP liposome is a PEG-PFOB-PEG-kaempferol combination, namely a DTP@PPPK liposome, and the DTP@PPPK liposome can fully exert the efficacy and improve the safety.

The application provides a repellent and contact-killing tick composition and a preparation method and application thereof. The repellent and contact-killing tick composition comprises plant essential oil and DEET; the repellent and contact-killing tick composition comprises a plant essential oil component; the plant essential oil and DEET are mixed to have a good synergistic effect; on the basis of the repellent effect of DEET, the contact-killing effect is increased. The repellent and contact-killing tick composition has a long repellent time, good safety, and reduced toxicity of DEET. The application screens plant essential oil with effective repellent and contact-killing effects, mixes the plant essential oil with DEET, reduces the DEET content in the repellent and contact-killing tick composition, reduces the toxic effect of DEET while having the same repellent effect, and increases the contact-killing effect of ticks. The repellent and contact-killing tick composition has a long repellent time and good contact-killing effect, can replace existing organic insect repellents and insecticides, and solves the problem of tick drug resistance.

Disclosed herein are poly(hydroxylalkyleneimine disulfide)polymers, which have both desirable transfection properties and reduced toxicity.

A ketorolaco derivative as shown in formula (I) has a better half-life and stability, has good pharmacokinetic properties, and has a higher stability in vitro; and as a preparation, the ketorolaco derivative can enhance efficacy and reduce toxicity. The present invention well improves the defects of frequent administration, gastrointestinal side effects, poor compliance and the like in traditional ketorolaco preparations.

Disclosed is a simplified, readily scalable series of individual methods that collectively constitute a method for the synthesis of C2'epiAmB, an efficacious and reduced-toxicity derivative of amphotericin B (AmB), beginning from AmB. Also provided are various compounds corresponding to intermediates in accordance with the series of methods.

The invention relates to a Tibetan medicine compound preparation for relieving stomach discomfort and protecting gastric mucosa. The Tibetan medicine compound preparation is prepared from 11 medicinal materials including gypsum rubrum (prepared), safflower carthamus, liquorice and the like through a special process. The core innovation is as follows: gypsum rubrum is processed by co-melting borax, potassium nitrate and aconite, a high-dissolution-rate calcium-boron compound is generated, and the toxicity is reduced; the highland barley wine and the yellow milk cooperate to form a gastric mucosa protective film. The medicinal materials are subjected to dynamic three-stage ultrasonic extraction (300 W to 200 W to 200 W) to realize graded dissolution of fat-soluble and heat-sensitive components, and the purity of the effective components reaches 98% in combination with a membrane filtration system (5 mu m to 0.45 mu m to 0.2 mu m). According to the compound, three-axis synergy of acid-relieving and pain-relieving (the pH value is increased to 3.5-4.0 in 30 minutes), blood-activating and film-protecting (the DPPH clearance rate is 89%) and qi-regulating and distention-eliminating (the helicobacter pylori MIC value is 0.5 mg / mL) is adopted, and nitrogen-filled packaging (the stability is 18 months) and palatability optimization (the compliance is 92%) are adopted as auxiliary materials. The acute toxicity LD50 is greater than 5g / kg, the long-term toxicity does not cause liver and kidney injury, the bottleneck of side effects of western medicines is broken through, and the traditional Chinese medicine is suitable for health care and adjuvant therapy of stomachache, sour regurgitation and other symptoms.

This invention discloses the preparation method and application of lipid prodrugs and self-microemulsion formulations of taxane compounds, belonging to the field of pharmaceutical technology. This invention discloses two lipid prodrugs substituted with long-chain fatty acids at positions 1,3, bridged by disulfide bonds, as shown in the following formula. The aim is to improve the oral absorption efficiency of ralotathol and SB-T-1214, promote their specific release at the target site, and achieve synergistic effects and reduced toxicity. The self-microemulsion drug delivery system is suitable for lipid-soluble drugs and has advantages such as simple preparation process, high drug loading, and easy process scale-up. The prepared self-microemulsion formulation consists of ralotathol or SB-T-1214 lipid prodrugs and excipients. The excipients include an oil phase and an emulsifier. By mass percentage, the oil phase accounts for 40-75% of the self-microemulsion formulation, the emulsifier accounts for 25-60%, and the ralotathol or SB-T-1214 lipid prodrug accounts for 1-10% of the total mass of the excipients.

This application concerns pharmaceutical compositions comprising cannabinoids which are suitable for subcutaneous administration in human subjects. Thus, this application concerns pharmaceutical compositions for subcutaneous administration. The pharmaceutical compositions according to the invention are particularly suitable for subcutaneous administration, which is advantageous for improving bioavailability and reducing toxicity.

The present application relates to a nanocomposite preparation apparatus and a nanocomposite prepared using same, and a nanocomposite preparation apparatus of the present application can prepare a nanocomposite having excellent stability by reducing toxicity while maintaining antibacterial properties of conventional antibacterial metals.

This invention relates to an anti-CD3 antibody or its antigen-binding fragment that specifically binds to CD3 in humans and non-human primates. The anti-CD3 antibody or its antigen-binding fragment has enhanced or reduced affinity, enabling improved efficacy or reduced toxicity. Furthermore, it allows for selective adaptation to the target when constructing a bispecific antibody, providing flexible adaptation design in drug development. The invention also relates to conjugates, fusions, bispecific antibodies, or pharmaceutical compositions containing the above-mentioned anti-CD3 antibody or its antigen-binding fragment. The invention also relates to nucleic acids encoding the antibody, host cells containing the nucleic acid, and methods for producing the antibody. Furthermore, the invention relates to the use of these CD3-binding antibodies for the prevention or treatment of cancer, infectious diseases, or autoimmune diseases in subjects.

The present invention provides novel CD3 antigen binding fragments with particularly advantageous properties such as producibility, stability, binding affinity, biological activity, specific targeting of certain T cells, targeting efficiency, remaining tumor cell killing and reduced toxicity. The present invention also provides bispecific antigen binding molecules for activating T cells. In addition, the invention further provides methods of treating cancer in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising the above said bispecific antigen binding molecules.

The invention discloses a ligand drug conjugate as well as a preparation method and application thereof. The present invention provides a compound of formula I, a pharmaceutically acceptable salt, a stereoisomer, a solvate or a solvate of the pharmaceutically acceptable salt thereof. The antibody drug conjugate provided by the invention has one or more of the following advantages: (1) the antibody drug conjugate provided by the invention has high stability in circulation, and the shedding of non-targeted drugs in non-target cells is reduced; (2) the antibody drug conjugate provided by the invention can increase effective release of bioactive molecules in cells so as to achieve the purposes of effect enhancement and toxicity reduction; (3) the antibody drug conjugate provided by the invention has good tumor tissue targeting property; and (4) the antibody drug conjugate disclosed by the invention has a good treatment effect on a tumor animal model.

The present invention provides attenuated immunostimulatory bacteria whose genome is modified to, for example, reduce toxicity and increase anti-tumor activity, such as by increasing accumulation in the tumor microenvironment, particularly in tumor-resident myeloid cells, increasing resistance to complement inactivation, reducing immune cell death, promoting adaptive immunity, and enhancing T cell function. The increase in phagocyte colonization improves delivery of encoded therapeutic products to the tumor microenvironment and into the tumor, and allows for routes of immunostimulatory bacteria administration such as systemic administration.

Disclosed are a compound represented by formula I or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition and use thereof. The compound has significant liver targeting characteristics, and can reduce the drug concentration in the circulating system while improving the efficacy, thereby reducing the toxic and side effects.

Provided are RNAi involving siRNA, shRNA or antisense oligonucleotide (ASO) that reduce the expression of toxic KIF1A alleles, thereby reducing the production of mutant KIF1A, for use in the treatment of KAND. Also provided are RNA targeting oligonucleotides that reduce the expression of toxic KIF1A alleles herein incorporate sequences that target common benign single nucleotide polymorphisms (SNPs) that are cis present with one or more pathogenic KIF1A mutations.

This invention relates to an immunotoxin targeting hematologic malignancies and its application. The immunotoxin comprises a toxic molecule and a carrier. The toxic molecule is pumpkin protein or a mutant of pumpkin protein. The carrier contains an antibody, ligand, or polypeptide capable of binding to hematologic malignancies cells. The antibody comprises an antibody fragment or a small molecule antibody. This invention provides an immunotoxin targeting hematologic malignancies for the treatment of these malignancies. The immunotoxin using a pumpkin protein mutant as the toxic molecule exhibits enhanced specificity against hematologic malignancies cells with high target expression, significantly increased activity in killing target cells, and allows for a substantial reduction in dosage and toxicity. In summary, the immunotoxin targeting hematologic malignancies using a pumpkin protein mutant as the toxic molecule offers advantages in both synergistic effect and reduced toxicity, and has broad application prospects.

The present invention relates to a method for producing 1B or 1D omega-5 gliadin-deleted wheat and wheat produced thereby, and, specifically, to a method for producing and selecting 1B or 1D omega-5 gliadin gene-deleted wheat by using radiation. The method for producing 1B or 1D omega-5 gliadin-deleted wheat, according to the present invention, enables the production of a radiation breeding-based non-GMO mutant wheat or wheat breeding parental line while retaining agronomic traits similar to those of a wild-type wheat variety, and thus wheat with reduced toxicity to wheat-dependent exercise-induced anaphylaxis (WDEIA) can be produced for use in the production of processed wheat foods and the like, or a parental line for breeding wheat varieties with reduced toxicity to WDEIA can be produced.

This invention belongs to the field of pharmaceutical technology, and particularly relates to a pharmaceutical composition for treating pancreatic cancer and its preparation method. The pharmaceutical composition comprises, by weight, the following components: 20-25 parts gemcitabine, 0.3-0.5 parts pinocembrin, and 5-12 parts sophoridine derivative. This invention, by combining gemcitabine, sophoridine derivative, and pinocembrin, maintains synergistic antitumor activity while significantly reducing liver damage, achieving the dual goals of "enhanced efficacy and reduced toxicity."

The present invention pertains to the technical field of medicine. Specifically disclosed are a dolastatin analogue, a ligand-drug conjugate thereof, a preparation method therefor, and use thereof. According to the present invention, a toxin, a linker, and a linker moiety are separately optimized, and the compound is prepared by means of organic synthesis. Also disclosed is use of the compound and the ligand-drug conjugate thereof in preparing a medicament for preventing and treating diseases, the diseases including but not limited to hyperproliferative diseases and angiogenic diseases, such as cancer, chronic metabolic diseases, and cardiovascular diseases. Further disclosed is a drug / pharmaceutical composition. The ligand-drug conjugate of the present invention offers the following effects: high stability, reduced off-target-induced toxicity, an expanded therapeutic window, a good tumor tissue-targeting property, and an excellent in vivo anti-tumor effect, achieving reduced toxicity and enhanced efficacy. The present invention provides a research foundation for preparing ligand-drug conjugates with high efficacy and low toxicity, having broad application prospects.

The application discloses a tripterine derivative with a structure as shown in formula I, wherein R1 is selected from H, and R2 is an integer from 3 to 6. Compared with tripterine, the tripterine derivative has enhanced inhibition effect on tumor cells, significantly reduced toxicity, can target mitochondria, and can kill cells by increasing the ROS level in tumor cells. The application further discloses a use of the tripterine derivative in preparation of an anti-tumor drug. The application further discloses a use of the tripterine derivative in preparation of a mitochondria-targeting anti-tumor drug.

Provided are compositions and methods for treating cancers. It is demonstrated herein that mRNA molecules expressing an OX40 agonist protein and the IL-12 protein, when used in combination, achieve synergistic anti-tumor effects. Such synergistic effect is further enhanced when a soluble portion of the OX40 ligand (OX40L) is used as the agonist, instead of the full-length OX40L protein. The mRNA molecules are preferably synthetic and packaged in lipid nanoparticles for delivery. Whether delivered through intratumoral injections or injected by other routes, these mRNA molecules can effectively inhibit tumor growth at local as well as distal sites. In addition, with the increased anti-tumor efficacy, the combinations, in particular at a mass ratio of IL-12 to OX40L between 1:1 and 1:3, are associated with reduced toxicity. Interestingly, when GM-CSF is further added to the combination, the anti-tumor effects are further improved.