46406results about "Pharmaceutical non-active ingredients" patented technology

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of a DMPK allele comprising a disease-associated-repeat. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

The present disclosure provides compounds and pharmaceutically acceptable salts thereof, and methods of using the same. The compounds and methods have a range of utilities as therapeutics, diagnostics, and research tools. In particular, the subject compositions and methods are useful for reducing signaling output of oncogenic protein.

Provided is an antibody-drug conjugate for use in the treatment of cancer in which one or more KRAS mutants, particularly a KRAS G12V mutant, a KRAS G12D mutant, and a KRAS G12C mutant, are expressed. Also provided are a drug and a drug-linker conjugate for use in the antibody-drug conjugate.　The present inventors have produced an antibody-drug conjugate with which a heterocyclic compound represented by formula (II) and having an activity of inducing the decomposition of KRAS mutant proteins can be delivered to cancer in which EGFRs are expressed, the production being achieved by linking the compound to an anti-EGFR antibody. The present inventors have also discovered a drug-linker conjugate for use in the antibody-drug conjugate or a salt thereof. In cancer in which EGFRs are expressed, the antibody-drug conjugate induces the decomposition of one or more KRAS mutants, particularly a KRAS G12V mutant protein, a KRAS G12D mutant protein, and a KRAS G12C mutant protein, thereby inhibiting the KRAS mutants and exhibiting an anti-tumor effect.

This disclosure relates to dosage forms comprising bupropion hydrochloride, another salt form of bupropion, or the free base form of bupropion; dextromethorphan hydrobromide, another salt form of dextromethorphan, or the free base form of dextromethorphan, and a polymer. In some embodiments, the dosage form has no significant dose dumping of bupropion in the presence of ethanol in vitro. In some embodiments, the dosage form does not have a food effect for bupropion or dextromethorphan when taken with a high-fat meal in human subjects. Some embodiments include a method of treating a nervous system condition (such as depression, e.g., major depressive disorder, including treatment-resistant depression, agitation associated with Alzheimer's disease (or agitation associated with dementia of the Alzheimer's type), agitation associated with dementia, anxiety (or generalized anxiety disorder), neuropathic pain, or peripheral diabetic neuropathic pain) comprising, administering a dosage form described herein to a human being in need thereof.

Aspects of the disclosure relate to methods of reducing fatigue in a subject having myotonic dystrophy type 1 (DM1). Aspects of the disclosure relate to methods of treating one or more symptoms assessable by the MDHI (e.g., a GI symptom, myotonia, upper extremity function impairment, fatigue, mobility impairment, impairment in the ability to perform activities, pain, vision impairment, communication impairment, sleep impairment, emotional issues, cognitive impairment, social satisfaction impairment, social performance impairment, breathing impairment, swallowing impairment, and / or hearing impairment) in a subject having myotonic dystrophy type 1 (DM1). In some embodiments, the methods comprise administering to the subject a composition comprising complexes (e.g., muscle targeting complexes) comprising an oligonucleotide (e.g., a DMPK- targeting oligonucleotide) covalently linked to an antibody (e.g., anti-TfRl antibody).

The invention relates to a dialkyl imidazole bionic lipid compound and a preparation method and application thereof.The structure of the dialkyl imidazole bionic lipid compound imitates natural phospholipid design, alkyl with no less than 10 carbon atoms is modified on the fourth site and the fifth site of imidazole, and primary amines with different alkyl chain lengths are modified on the second site; the dialkyl imidazole bionic lipid compound is mixed with a therapeutic drug and other auxiliary materials to prepare lipid nanoparticles loaded with the therapeutic drug, and the lipid nanoparticles can be used as a drug delivery system for preparation of brain-targeted drugs. The dialkyl imidazole bionic lipid has the function of dynamically regulating and controlling the blood-brain barrier, and can realize reversible opening of the blood-brain barrier; the formed drug-loaded lipid composition can pass through a blood brain barrier and well realize brain-targeted delivery of loaded therapeutic drugs; the drug-loaded lipid composition composed of the dialkyl imidazole bionic lipid belongs to a new generation of bionic nano-drug carriers, and provides a new strategy for realizing brain-targeted delivery of different types of drugs.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to compositions comprising a plurality of complexes comprising an antibody (e.g., anti-TfRI antibody) covalently linked to one or more oligonucleotides (e.g. a DMPK targeting oligonucleotide), each oligonucleotide being covalently linked at a linkage site represented by a lysine (K) residue of the antibody. In some embodiments, the antibody comprises a heavy chain comprising a heavy chain variable region (VH) and a heavy chain constant region, and a light chain comprising a light chain variable region (VL) and a light chain constant region, wherein at least 80% (e.g., 80%-98%, 80%-95%, 80%-90%, 85%-98%, 85%-95%, 85%-90%, 90%-98%, 90%-95%, 95%-97%, or more) of the light chain constant regions of the antibodies of the complexes in the composition are independently covalently linked to an oligonucleotide at a linkage site represented by K188 (based on Kabat numbering) and / or a linkage site represented by K190 (based on Kabat numbering) of the light chain constant regions of the antibodies.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of a DMPK allele comprising a disease-associated-repeat. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Aspects of the disclosure relate to methods of reducing expression or activity of DMPK (e.g., reducing the level of a mutant or wild-type DMPK RNA, or the activity of a DMPK gene product) and / or methods of treating myotonic dystrophy (e.g., DM1) in a subject. In some embodiments, the methods comprise administering to the subject a composition comprising complexes (e.g., muscle targeting complexes) comprising an oligonucleotide (e.g., a DMPK—targeting oligonucleotide) covalently linked to an antibody (e.g., anti-TfR1 antibody).

This disclosure relates to homodimeric antibodies for use in treating cancer generally and to both homodimeric antibodies that bind human sperm protein 17 (Sp17) and homodimeric antibody immunoconjugates specifically. Such homodimeric antibodies display improved properties relative to monomeric antibodies, for example, because they can crosslink cells, improve cellular uptake, and / or carry greater payloads.

This disclosure relates to dimeric immunoconjugates for use in treating cancer generally and to dimeric immunoconjugates that bind human sperm protein 17 (Sp17) specifically. A dimeric immunoconjugate of this disclosure generally comprises a first monomeric antibody that carries a first payload and a second monomeric antibody that carries a second payload, wherein the first payload and the second payload are different. Such dimeric immunoconjugates advantageously allow the simultaneous delivery of two chemotherapeutics to a cancer cell, which allows for synergistic antineoplastic activity.

Systems and methods are provided for stabilization of cells and retention of biomolecules therein for further analysis. Block copolymers are inserted into membranes of biological particles, cell membranes or organelles (e.g., organelle membranes) and polymerized to form an intra-biological particle (e.g., intracellular) polymer network.

This disclosure relates to dosage forms comprising bupropion hydrochloride, another salt form of bupropion, or the free base form of bupropion; dextromethorphan hydrobromide, another salt form of dextromethorphan, or the free base form of dextromethorphan, and a polymer. In some embodiments, the dosage form has no significant dose dumping of bupropion in the presence of ethanol in vitro. In some embodiments, the dosage form does not have a food effect for bupropion or dextromethorphan when taken with a high-fat meal in human subjects. Some embodiments include a method of treating a nervous system condition (such as depression, e.g., major depressive disorder, including treatment-resistant depression, agitation associated with Alzheimer's disease (or agitation associated with dementia of the Alzheimer's type), agitation associated with dementia, anxiety (or generalized anxiety disorder), neuropathic pain, or peripheral diabetic neuropathic pain) comprising, administering a dosage form described herein to a human being in need thereof.

The present invention relates to an immunomicrobubble complex and its uses. The immunomicrobubble complex (IMC) according to the present invention comprises microbubbles conjugated with an antibody, wherein the microbubbles have excellent stability and excellent antibody binding strength, and it has been confirmed that when the immunomicrobubble complex is treated with high-intensity focused ultrasound (HIFU), the anti-tumor effect is significantly enhanced and an immune-enhancing effect is exhibited. Therefore, the immunomicrobubble complex according to the present invention is expected to improve the delivery efficiency of the conjugated antibody and can be used for the diagnosis and treatment of cancer, and exhibits various functions in the field of immunotherapy, including a contrast effect, improvement of half-life, improvement of drug delivery, lymphocyte concentrating effect, cancer immunotherapy, and ultrasound-induced immunotherapy.

The invention relates to a layered drug-loading microneedle patch as well as a preparation method and application thereof. The preparation method of the layered drug-loading microneedle patch comprises the following steps: S1, dissolving a drug and a soluble high-molecular polymer in a solvent according to a mass ratio of (2: 1)-(1: 12) to form a needle tip solution, then filling a needle tip cavity of a microneedle mold with the needle tip solution, drying, and removing redundant drug residues on the surface to form a drug-loading needle tip layer; and S2, filling a mold containing the drug-loading needle tip layer with a photocurable polymer, performing ultraviolet curing for 10-30 seconds under the wavelength of 365-405 nm, and then performing demolding to form a substrate layer, thereby obtaining the layered drug-loading microneedle patch. According to the method, one-time filling of the needle tip part is successfully achieved by combining needle tip auxiliary material proportion optimization, meanwhile, the curing process is rapid, the medicine utilization rate and the process stability are remarkably improved, the medicine stability is good, and the method is suitable for industrial production.

Embodiments of the present invention provide methods and intermediates for the large scale preparation of 2, 4, 6-trifluoro-N-[6-(1-methylpiperidine-4-carbonyl)-2-pyridyl] benzamide hemisuccinate, as well as formulations and product forms prepared by these methods. Embodiments of the present invention further provide for the preparation of lamidetan acetate (2, 4, 6-trifluoro-N-[6-(1-methylpiperidine-4-carbonyl)-2-pyridyl] benzamide acetate) and / or a pharmaceutical composition thereof, and / or the use of lamidetan acetate and formulations thereof in subcutaneous drug delivery.

The present disclosure describes improved LNP-based RNA vaccines, nucleobase editing systems, and therapeutics for use in treating and / or immunization against disease. In particular, the disclosure describes improved LNPs, including novel and improved ionizable lipids for making LNPs, that enhance the targeted delivery of LNP-based RNA vaccines and therapeutics based on linear and / or circular mRNAs. The improved LNPs protect linear and / or circular mRNA payloads from degradation and clearance while achieving targeted systemic or local delivery for use as enhanced vaccines and / or therapeutic agents.

The invention discloses an efficient-dissolution dotenorad tablet and a preparation method thereof, and relates to the technical field of tablet preparation. The tablet consists of 5-20 parts of a dotenorad active component, 10-30 parts of a disintegrating agent, 40-70 parts of a filling agent, 0.5-5 parts of a surfactant, 0.5-3 parts of a lubricant, 1-5 parts of an adhesive and 0.5-1 part of an antioxidant. The preparation method comprises the following steps: premixing active components and auxiliary materials, carrying out high-shear wet granulation to form porous structure particles, carrying out precise temperature-control drying through a fluidized bed, carrying out micronization treatment to regulate the specific surface area of the particles, and finally, carrying out high-pressure tablet forming through a magnesium stearate / aerosil compound lubrication system. The dissolution rate of the tablet in a medium with the pH value of 6.8 for 15 minutes reaches 85% or above, meanwhile, long-term stability is achieved by inhibiting oxidative degradation, and the tablet has the dual advantages of quick effect taking and stable storage.

Disclosed are compositions of lipid nanoparticles (LNP) comprising an ionizable cationic lipid, a phospholipid, a sterol, and a PEG-lipid (non-functionalized and optionally functionalized). The functionalized PEG-lipid can be conjugated with a binding moiety to create a targeted LNP (tLNP). The disclosed tLNP preferentially deliver a nucleic acid molecule or other negatively charged payload to cells expressing a cell surface antigen recognized by the binding moiety of the tLNP, and are better tolerated, as compared to LNPs and tLNPs comprising ionizable cationic lipids found in marketed pharmaceuticals comprising LNPs.

Pharmaceutical compositions for the transmucosal delivery of N-N-dimethyltryptamine (DMT) acceptable salt or prodrug thereof in combination with a monoamine oxidase inhibitor to achieve desired bioavailability suitable for the treatment of neurological disorders.

The invention belongs to the field of medicines, particularly relates to the technical field of targeted delivery lipids, and particularly discloses an ionizable cationic lipid targeting immune cells, a composition containing the ionizable cationic lipid and application of the ionizable cationic lipid. The immune cell targeting cationic lipid provided by the invention has a structure as shown in formula (I), can be used for RNA targeting delivery, and can significantly enhance the targeting effect of mRNA drugs on immune cells. # imgabs0 #

This disclosure relates to dosage forms comprising bupropion hydrochloride, another salt form of bupropion, or the free base form of bupropion; dextromethorphan hydrobromide, another salt form of dextromethorphan, or the free base form of dextromethorphan, and a polymer. In some embodiments, the dosage form has no significant dose dumping of bupropion in the presence of ethanol in vitro. In some embodiments, the dosage form does not have a food effect for bupropion or dextromethorphan when taken with a high-fat meal in human subjects. Some embodiments include a method of treating a nervous system condition (such as depression, e.g., major depressive disorder, including treatment-resistant depression, agitation associated with Alzheimer's disease (or agitation associated with dementia of the Alzheimer's type), agitation associated with dementia, anxiety (or generalized anxiety disorder), neuropathic pain, or peripheral diabetic neuropathic pain) comprising, administering a dosage form described herein to a human being in need thereof.

Compounds or their pharmaceutically acceptable salts can modulate the G12D mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds disclosed herein or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

The invention discloses a bovine I-type alpha interferon-ferritin fusion protein, a mutant thereof, a preparation method and an application of the bovine I-type alpha interferon-ferritin fusion protein. The bovine I-type alpha interferon is fused with a ferritin subunit, and interferon molecules are highly repeatedly and orderly displayed on the surface of a ferritin nanocage by utilizing the self-assembly characteristic of ferritin, so that the expression level, the structural stability and the antiviral activity of the interferon are remarkably improved. The fusion protein is further subjected to single-site or multi-site rational design mutation, and a mutant with significantly improved antiviral activity and stability is obtained. According to the invention, a silkworm or insect cell eukaryotic expression system is adopted to express the fusion protein or the mutant thereof, and the expression system is safe to operate, simple and convenient in procedure, low in cost and extremely beneficial to large-scale industrial production; the prepared fusion protein or mutant nanoparticles have application prospects in preparation of drugs or reagents for preventing or treating bovine viral diseases.

The invention provides a preparation method of mitochondria-targeted antioxidant hybrid vesicles. The preparation method comprises the following steps: S1, preparing and separating adipose-derived stem cell nano-vesicles; s2, preparing a liposome loaded with dihydromyricetin and distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000-triphenylphosphine targeting peptide by an ethanol injection method; and S3, preparing the hybrid nano vesicles loaded with the dihydromyricetin and the distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000-triphenylphosphine targeting peptide. The invention also provides the hybrid vesicles prepared by the method and application of the hybrid vesicles in preparation of refractory diabetes wound treatment drugs. The lipidosome and the adipose-derived stem cell nano-vesicles are hybridized to prepare the hybridized vesicles capable of targeting mitochondria and resisting oxidation, the hybridized vesicles are applied to wound treatment for the first time, the problem of oxidative stress of diabetic wounds is solved, wound healing is accelerated, and a new strategy is provided for optimizing mitochondrial function defects and oxidative stress of the diabetic wounds.

The invention provides a metal polyphenol nanoparticle, a preparation method thereof and an application of the metal polyphenol nanoparticle in preparation of a medicine for treating acute lung injury, the metal polyphenol nanoparticle is formed by self-assembly of metal ions and polyphenol, the metal ions are selected from Mg < 2 + >, Zn < 2 + >, Mn < 2 + > or Cu < 2 + >, and the polyphenol is selected from Mg < 2 + >, Zn < 2 + >, Mn < 2 + > or Cu < 2 + >. The polyphenol is selected from epigallocatechin gallate (EGCG), caffeic acid (CA), chlorogenic acid (CGA), gallic acid (GA) and luteolin (LUT). The metal polyphenol nanoparticles are used for preparing a medicine for treating acute lung injury induced by sepsis, pneumonia, serious trauma or inhalation injury, and the medicine further comprises a pharmaceutically acceptable carrier. The metal polyphenol nanoparticles provided by the invention are simple in preparation process and high in biological safety, polyphenol and metal ions synergistically enhance the anti-inflammatory and antioxidant activity, and the metal polyphenol nanoparticles are superior to the single use of polyphenol or metal ions.

Compounds are provided having the following structure:or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein a, b, c, d, G1, G2, L1, L2, R1a, R1b, R2a, R2b, R3a, R3b, R4a, R4b, R5, R6, R7, R8 and X are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, nanoparticles comprising the compounds and methods for their use and preparation are also provided.