168 results about "Reduced toxicity" patented technology

The invention provides a preparation method and application of a high-efficiency encapsulated pH-responsive drug-loaded liposome. According to the method, two-phase fluid of a medicine aqueous solution and a lipid component organic solution in a micro-channel is accurately controlled, and the efficiently encapsulated liposome is prepared from bottom to top by utilizing a micro-mixing technology. Compared with a conventional passive drug loading method which is relatively low in encapsulation efficiency in preparation of hydrophilic drug nano-liposomes, the method provided by the invention can improve the encapsulation efficiency to be close to 95% under optimized prescription and process conditions. According to the invention, by adjusting the proportion of each component in the prescription and the preparation process, the release behavior of liposome drugs such as adriamycin and the like can be adjusted, and the drug release shows pH responsiveness. Through efficient encapsulation of adriamycin and the like and pH-responsive release of the liposome dosage form, the effects of efficacy enhancement and toxicity reduction are achieved in the anti-tumor treatment aspect.

Amphotericin B (AmB) is the gold standard for treatment of life-threatening systemic fungal infections. To develop cost-effective AmB formulations with reduced toxicity, embodiments disclosed introduce controlled number of phenylboronic acid (PBA) moieties into telodendrimer (TD) nanoplatform for optimizing AmB conjugation via reversible boronate ester strategy. This multivalent flexible boronate TD nanoplatform can also be applied in developing prodrugs for different cis-diol containing or α- or β- hydroxyl ketone-containing drug molecules.

The present disclosure concerns immunomodulatory compositions and methods of use for enhancing response to an antigen (e.g., in a vaccine), an immunotherapy (e.g., a cancer immunotherapy), or other immune stimulation. The disclosure describes immunomodulators having reduced toxicity and improved immune response compared with existing adjuvants. Further disclosed are methods for improving an immune response to a vaccine antigen, cancer immunotherapeutic, or other immune stimulating agent. The disclosure describes dimeric and polymeric immunomodulators comprising one or more pattern recognition receptor (PRR) agonist moieties and one or more NF-κB inhibitor moieties.

Aspects of the disclosure relate to compositions and methods for treating spinal muscular atrophy (SMA). The disclosure is based, in part, on isolated nucleic acids and vectors (e.g., viral vectors, such as rAAV vectors) encoding SMN1. In some embodiments, the expression of SMN 1 is driven by a native SMN 1 promoter or a variant thereof. In some embodiments, isolated nucleic acids and vectors of the disclosure have reduced toxicity and / or increased transgene expression relative to previously described SMN-encoding vectors.

The disclosure provides RNA therapeutics, e.g. RNA molecules for treating or preventing an infection, and methods for reducing inherent toxicity of antigens or cytotoxicity exhibited by certain microbial antigens or immunogenic variants thereof when expressed intracellularly from RNA, as well as compositions comprising RNA therapeutics produced by such methods. The RNA encoding the antigens, immunogenic variants or fragments thereof is formulated and administered in a way that the antigens, variants or fragments are produced by cells of a subject, in particular after intramuscular or intravenous administration of the RNA and that, at the same time, toxicity or cytotoxicity is avoided.

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.

Disclosed are cationic polymers comprising monomers such as those described in Formula (I),Such polymers can be useful for the preparation of therapeutic compositions (e.g., compositions comprising nucleic acids such as mRNA). Additionally, therapeutic compositions comprising these cationic, biodegradable polymers can have improved properties and reduced toxicity.

Provided herein are locoregional therapies using conjugates of therapeutic agents that demonstrate extended release of the native therapeutic agents, as well as methods for the manufacture of such conjugates. These conjugates may be useful in the treatment of various conditions and diseases that respond to the extended exposure to the therapeutic agents, or for delivery of therapeutic agents that suffer from undesired systemic toxicities. In certain embodiments, the locoregional therapy is intratumoral therapy, which may be combined with a systemic or local therapy for enhanced therapeutic efficacy and reduced toxicity of the combined agents.

Provided are intermittent dosing methods for treating a condition associated with increased 15-hydroxyprostaglandin dehydrogenase (15-PGDH) activity or expression levels in a subject with a 15-PGDH inhibitor to reduce toxicity. Further, provided herein are methods of treating a condition associated with increased 15-hydroxyprostaglandin dehydrogenase (15-PGDH) activity or expression levels in a subject by administering a 15-PGDH inhibitor when the plasma concentration of the 15-PGDH inhibitor in the subject falls below the EC50 of the 15-PGDH inhibitor, while maintaining therapeutic efficacy of the 15-PGDH inhibitor.

The present disclosure is directed to cell penetrating peptides, including cyclic cell penetrating peptides with high cytosolic delivery efficiency and reduced toxicity that are able to effectively deliver cargo inside a cell to treat a variety of conditions and diseases.

An interferon (IFN)-anti-PD-L1 fusion protein, a pharmaceutical composition and a kit containing the same for treating tumors are disclosed. The fusion protein of the present invention can simultaneously target PD-L1 and IFN receptors, and the activation of IFN signals in a tumor microenvironment (TME) can enhance the PD-1 / PD-L1 therapy against tumors by inducing stronger T cell activation. The anti-PD-L1 antibody can be used to specifically deliver immunomodulatory molecules to tumor tissues, and the fusion protein results in the generation of multiple feedforward responses, which can increase the targeting effect, reduce the toxicity, and enhance the response to IFN therapy, thereby maximizing the anti-tumor effect.

The invention discloses a preparation method and application of a response type cationized two-dimensional nano catalytic transfection agent, and belongs to the field of biology. According to the transfection agent disclosed by the invention, two-dimensional MXene (such as niobium carbide) is taken as a matrix, and the surface of the matrix is sequentially modified with a multi-amino cationic polymer (such as dendritic polyethyleneimine) and aldehyde group polyethylene glycol (CHO-PEG-CHO), so that PNb2C (at) PEG with pH responsiveness is formed. The preparation method comprises the steps of Nb2C nanosheet stripping, PEI cationization, PEG shielding modification and the like. Material characterization shows that the potential of the transfection agent is-12.5 mV (shielding positive charges) when the pH value is 7.4, the potential of the transfection agent is converted into + 14.0 mV (responding to a tumor acidic microenvironment) when the pH value is 6.5, and the transfection agent has the capability of catalyzing decomposition of active oxygen and can protect cells from oxidative damage. Compared with the traditional cationic liposome, the transfection efficiency is equivalent, but the toxicity is obviously reduced, the raw material cost is low, the gene load is high, and the cationic liposome is suitable for the field of gene delivery.

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.

Provided in the present invention is a high-efficiency and low-toxicity DNA and RNA lipid delivery carrier. In order to enrich the types of nucleic acid drug delivery carriers, improve the in-vivo delivery and expression effects of the nucleic acid drug and reduce the toxicity and side effects, a new ionizable lipid compound having a special structure is provided in the present invention. The compound has a good binding effect with a negatively-charged nucleic acid, which effectively prevents the premature degradation of the nucleic acid by a nuclease in a cell and facilitates the passage of a liposome loaded with the nucleic acid through a cell membrane. Effective degradation and rapid removal can be achieved, the toxicity and side effects of the nucleic acid drug are reduced, and a nucleic acid drug delivery carrier truly having a high transfection efficiency, a high expression level and a low toxicity can be formed.

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.

The invention provides a composition for inhibiting tumor growth and a preparation method thereof, and belongs to the technical field of medicines. After selenium is loaded, folic acid is coupled, and folic acid-selenium polysaccharide nanoparticles are prepared; notoginsenoside, curcumin, alizarin and hairyvein agrimony phenolic acid are embedded in pH-sensitive lipidosome, and the pH-sensitive lipidosome is uniformly mixed with folic acid-selenium polysaccharide nanoparticles and semicarbazone compounds to prepare the composition for inhibiting tumor growth. The composition for inhibiting tumor growth prepared by the invention has a relatively good anti-tumor effect, can release active components in a targeted manner at a tumor part, can reverse drug resistance, reduce the dosage of chemical drugs, reduce toxicity and improve patient compliance, is high in bioavailability, and has a wide application prospect.

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 are C16 amide derivatives of C2'-epi-amphotericin B (C2'epiAmB) and salts thereof, characterized by improved clinical efficacy and reduced toxicity compared to AmB. Also disclosed are pharmaceutical compositions comprising any of the disclosed compounds or salts thereof, as well as treatment methods and therapeutic uses of the pharmaceutical compositions.

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.

The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. In preferred embodiments, the antibody may be an hRS7 antibody. The methods and compostions are of use to treat Trop-2 expressing cancers in human patients, preferably in patients who are resistant to or relapsed from at least one prior anti-cancer therapy, more preferably in patients who are resistant to or relapsed from treatment with irinotecan. The immunoconjugate may be administered at a dosage of 3 mg / kg to 18 mg / kg, preferably 8 to 12 mg / kg, more preferably 8 to 10 mg / kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size and reduce or eliminate metastases. Preferred tumors to treat with the subject immunoconjugates include triple-negative breast cancer, HER+, ER+, progesterone+ breast cancer, metastatic non-small-cell lung cancer, a metastatic small-cell lung cancer and metastatic pancreatic cancer.