33 results about "Tumor Necrosis Factor Suppression" patented technology

This invention is directed to derivatives of piperidine-2,6-dione, or their organic or inorganic salts thereof, a methods of synthesis of these derivatives, and their application as active pharmaceutical ingredient as inhibitors of TNFα releasing in cells, the derivative of piperidine-2,6-dione being of the general formula (I): wherein n represents 1, 2, 3, 4, 5 or 6; R1 represents from one to four of the same or different substituents selected from F, Cl, Br, C1-4 alkyl, OH, OC1-4 alkyl, NO2, NHC(O)C1-4 alkyl, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2; R2 represents OR3, NR3R4, N(R3)COR4, O2CR5; R3 and R4 represent independently and at each occurrence H or C1-4 alkyl; R5 represents CHR6NR7R8, CHR6NR9C(O)CHR10NR7R8, a heterocycle W or CHR6NR9C(O)W; R6, R9, R10 represent independently and at each occurrence H, or C1-4 alkyl; R7 and R8 represent independently and at each occurrence H, C1-4 alkyl, or R7 and R8 taken together represent 1,3-propylene, 1,4-butylene, 1,5-pentylene, or 1,6-hexylene; W represents four-membered, five-membered, six-membered, seven-membered, or eight-membered saturated or unsaturated heterocycle.

Extracts of various species of the Moraceae family have estrogenic properties. For example, aqueous and ethanolic extracts of Ligustrum lucidum Ait. of the Oleaceae Family possess estrogenic properties in both ERα+ and ERβ+ cells. These estrogenic effects include estrogen response element (ERE) stimulation as well as tumor necrosis factor (TNF) repression. Methods are provided for treating climacteric symptoms, breast and / or uterine cancer, and osteoporosis.

The invention discloses a composition of nanoparticles composed of positively charged chitosan, one negatively charged substrate, and optionally a zero-charge compound or at least one tumor necrosis factor inhibitor for oral delivery. The chitosan-based nanoparticles are characterized with a positive surface charge and enhanced permeability for oral drug delivery.

The present invention relates to a group of new oligonucleotides sequences with human tumor necrosis factor α (TNF-α) inhibiting activity, which includes DNA sequences and RNA sequences. These oligonucleotides or aptamer can specifically be bound to TNF-α and inhibit the cytoxicity of TNF-α to L929 cells. Therefore, the aptamer of the present invention may be used to detect TNF-α and provide a therapeutic method for diseases related to the increasing level of TNF-α. Compared with other TNF antagonists such as monoclonal antibody and soluble receptor, the present invention has high specificity, high affinity, quick penetration to target tissue, rapid plasma clearance, and lower immunogenecity. Turthermore, it can be used repeatedly and keeps high concentration in target tissue and the like. It has the advantages of affinity and specificity similar to monoclonal antibodies and also has permeability and pharmacokinetics characteristics similar to small molecular polypeptide. The present invention also refers to derivative of the oligonucleotides sequence, including modified sequence. The present invention may further be manufactured as medicine for therapy and diagnosis of TNF-α related diseases.

The invention relates to clinical application of a substituted aryl hydrazone compound and a derivative thereof serving as an anti-tumor necrosis factor inhibitor. A test result shows that the compound has a lower cytotoxicity in animal bodies, so the medical compound is expected to be used as an anti-TNF-alpha and TNF-beta inhibitor in the clinical application and is mainly used for treating some TNF related immunological diseases such as rheumatic arthritis, inflammatory bowel diseases, diabetes, hematosepsis, psoriasis, ankylosing spondylitis and some communicable diseases including HIV. A current TNF related research also shows that the medical compound can be used for treating clinical blood and solid tumor such as myelodysplastic syndrome, myelofibrosis, acute bone marrow cell leucocythemia, acute / chronic graft-versus-host reaction, ovarian cancer, nephrocyte cancer and the like.

Taught are derivatives of 5H-thioeno(3,4-c)pyrrole-4,6-dione, their organic, and inorganic salts, methods of synthesis of these derivatives, and their application as active pharmaceutical-ingredients useful as inhibitors of TNFα, the derivative being represented by the general formula (I):in which R1 represents H, C1-6alkyl, OR4, OC(O)R5, NO2, NHC(O)R6, or NR7R8; R2 represents H, a halogen, or C1-6alkyl; R3 represents H, methyl, isopropyl, allyl, benzyl, CH2CO2(C1-6alkyl), or CH2(CH2)nR9; R4, R5, R6, R7, and R8 each independently and at each occurrence represents H, or C1-6alkyl; R9 represents H, C1-6alkyl, OH, OC1-6alkyl, NH2, NHC1-6alkyl, N(C1-6alkyl)2, or CO2(C1-6alkyl); and n represents 1, 2, 3, or 4.

Recombinant DNA encoding Tumor Necrosis Factor (TNF) Inhibitory Protein, or an active fragment thereof, is obtained. The TNF Inhibitory Protein has the ability to inhibit: (a) the binding of TNF to its receptors, and (b) the cytotoxic effect of TNF. TNF Inhibitory Protein and salts, functional derivatives and active fractions thereof can be used to antagonize the deleterious effects of TNF by eliminating TNF from the body, and to reduce the cytotoxic activity of TNF by binding to TNF and thereby to inhibit the binding of TNF to its receptors. The DNA may be in an expression vector. Host cells transfected with such an expression vector may be used to produce the TNF Inhibitory Protein.

This invention is directed to derivatives of piperidine-2,6-dione, or their organic or inorganic salts thereof, a methods of synthesis of these derivatives, and their application as active pharmaceutical ingredient as inhibitors of TNFα releasing in cells, the derivative of piperidine-2,6-dione being of the general formula (I):wherein n represents 1, 2, 3, 4, 5 or 6; R1 represents from one to four of the same or different substituents selected from F, Cl, Br, C1-4 alkyl, OH, OC1-4 alkyl, NO2, NHC(O)C1-4 alkyl, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2; R2 represents OR3, NR3R4, N(R3)COR4, O2CR5; R3 and R4 represent independently and at each occurrence H or C1-4 alkyl; R5 represents CHR6NR7R8, CHR6NR9C(O)CHR10NR7R8, a heterocycle W or CHR6NR9C(O)W; R6, R9, R10 represent independently and at each occurrence H, or C1-4 alkyl; R7 and R8 represent independently and at each occurrence H, C1-4 alkyl, or R7 and R8 taken together represent 1,3-propylene, 1,4-butylene, 1,5-pentylene, or 1,6-hexylene; W represents four-membered, five-membered, six-membered, seven-membered, or eight-membered saturated or unsaturated heterocycle.

The invention provides an application of japonicone A (chemical structural formula I) in preparation of tumor necrosis factor (TNF) inhibitor drugs. The japonicone A is inula japonica extract. In the invention, by adopting a reverse docking technology for virtual screening, the result shows that TNF-alpha is potential binding protein of the japonicone A; by adopting a BIACORE technology, the result shows that the japonicone A can be directly combined with TNF-alpha coupled on a chip, and can inhibit the combination of the TNF-alpha and the TNF-R (receptor) coupled on a sensor chip; and furthermore, an experiment confirms that the japonicone A can be directly combined with the TNF-alpha and can inhibit the interaction of the TNF-alpha and the TNF-R, thus the japonicone A can be used for preparing TNF inhibitor drugs. The drug provided by the invention is a pharmaceutical composition prepared from a medicinal carrier and the japonicone A used as an active ingredient. The pharmaceutical composition can be used for treating TNF-related diseases such as osteoarthropathy, asthma, bronchitis, allergic rhinitis and the like, thereby providing a new way for treating the diseases and obtaining greater clinical application values.

The invention relates to a reagent and a method for predicting the curative effect of the tumor necrosin inhibitor. Particularly, the invention provides application of a reagent and / or an instrument to the preparation of a product for predicting the curative effects of treating patients with ankylosing spondylitis by using tumor necrosin inhibitors, wherein the reagent and / or instrument comprisesa tail end galactosylation level of the blood IgG surface double-antenna complicated N sugar chain, wherein the tail end galactosylation level is double-antenna complicated N-sugar chain level Ga10 connected with no galactose at the tail end, a double-antenna complicated N-sugar chain level Gal1 connected with one galactose at the tail end and a double-antenna complicated N-sugar chain level Gal2connected with two galactoses at the tail end on the IgG surface.

The present invention relates to Tumor Necrosis Factor-alpha (TNF-alpha or TNF-α) inhibiting peptides and process for the preparation thereof. The present invention further relates to a pharmaceutical composition comprising TNF-alpha inhibiting peptides of the present invention and uses thereof in treating TNF-alpha mediated inflammatory disorders.

Disclosed are methods of treating an autoimmune or inflammatory disease using a composition comprising an isolated antibody or an antigen-binding fragment or variant thereof that is capable of binding to muramyl peptide, derivative, analog or salt thereof, wherein said muramyl peptide comprises muramic acid and an amino acid selected from the group consisting of alanine, isoglutamine, glutamic acid and a salt thereof. In one preferred embodiment, the composition can comprise of the isolated antibody or an antigen-binding fragment and one or more therapeutic agents such as Tumor Necrosis Factor (TNF) inhibitor. The autoimmune or inflammatory disease is selected from a group consisting of sepsis, septic shock, Crohn's disease, rheumatoid arthritis, asthma, allergy, atopic disorders, multiple sclerosis, pertussis, gonorrhea, inflammatory bowel disease, and antibiotic associated disorder.

The present invention relates to ex vivo methods for preserving / maintaining blood vessels that are to be used as vascular grafts by inhibiting TNF-α. The present invention also relates to compositions comprising an inhibitor of a TNF-α for use in the methods of the invention, which compositions are free of active TGF-β or does not contain active TGF-β in an amount greater than endogenous blood levels.

The embodiment of the invention discloses a cosmetic composition. The cosmetic composition comprises a plant extract having tumor necrosis factor inhibitor activity, a plant extract having antioxidative activity, and polypeptide having wrinkle resisting activity, wherein the polypeptide is selected from one or more of KTTKS, KTTKSF, GEKG, GEKGF, EEMQRR and EEMQRRF. Through mutual cooperation of various components, the cosmetic composition can start three ways of neutralizing inflammatory factors, eliminating oxygen free radicals and stimulating collagen tissue which is destructed or broken, intercellular substances and the like in a fibroblast proliferation derma layer after being used, so that the problem of skin ageing can be comprehensively prevented, delayed and alleviated, and the cosmetic composition has favorable technical effects and favorable application prospects.

The invention belongs to the technical field of pharmaceutical chemistry and medicine, relates to a novel tumor necrosis factor (TNF-alpha) inhibitor and particularly relates to a small molecule 3-aryl-1-indanone derivative TNF-alpha inhibitor and its medicinal use. The invention provides the 3-substituted-1-indanone derivative compound shown in the following formula (1). An in-vitro experiment result shows that the prepared derivative compound has specific inhibition effects on a tumor necrosis factor (TNF-alpha) produced by LPS-stimulated macrophages RAW 264.7. The derivative can be used for preparation of a small molecule treatment drug for treating ulcerative colitis and as a small molecule TNF-alpha inhibitor and can be used for treating human TNF-alpha increasing-mediated immunoinflammatory diseases such as ulcerative colitis, Crohn's disease, rheumatoid arthritis, osteoarthritis and psoriasis.

The inhibitory oligonucleotides with partial phosphorothioation with reduced toxicity strongly block NF-kB activation induced by TLR9 agonists and TLR7 / 8 agonists. The production of proinflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFa), is inhibited by the inhibitory-oligonucleotides. Interferon (IFN) production from human PBMC induced by TLR9 agonist is prevented by the inhibitory-oligonucleotides. These oligonucleotides can be used as a remedy for the treatment of immune-mediated disorders such as rheumatoid arthritis, systemic lupus erythematosus (SLE), sepsis, multiple organ dysfunction syndromes and inflammatory cytokine-mediated inflammatory disease.

Disclosed herein are methods for the treatment of an individual having an inflammatory bowel disease (“IBD”). The disclosed methods may include the detection of Oncostatin M (OSM) in a biological sample obtained from an individual having an IBD. The detection of OSM may be used to characterize the individual as a tumor necrosis factor (TNF) inhibitor (TNFi) responder or a TNFi non-responder for selection of appropriate treatment.

The present invention relates to methods for identifying patients that will respond to treatment with anti-TNF-therapy, i.e., anti-TNF responder patients. In particular, the present invention relates to determining response to an inhibitor of tumor necrosis factor (TNF) in a patient with a chronic inflammatory disease by determining the activity of type I interferon in the patient. The invention further relates to quantification of type I interferon as a measure of predicting responsiveness to anti-TNF therapy in patients with a chronic inflammatory disease such as rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, juvenile chronic arthritis, lupus, Crohn's disease, as well as for cardiovascular disease.

The invention discloses a gene polymorphism detection kit for predicting the efficacy of a tumor necrosis factor alpha inhibitor as well as a detection method and application of the gene polymorphism detection kit. The efficacy of the tumor necrosis factor alpha inhibitor reflects the metabolic capability by detecting the polymorphism of a TNF alpha G308A gene; according to the kit, a specific amplification primer and a sequencing primer are designed aiming at the polymorphism of TNF alpha G308A, and the kit comprises the following components: a sample treatment solution, magnetic beads, an amplification reagent 1, an amplification reagent 2, the TNF alpha G308A sequencing primer and a positive control. On one hand, a mode of extracting and amplifying in the same tube is adopted, so that the risk of nucleic acid loss due to repeated tube transfer during extraction is avoided; on the other hand, rapid isothermal amplification is carried out by adding an anti-inhibitor; the invention aims to detect the gene polymorphism of the efficacy of the tumor necrosis factor alpha inhibitor by combining constant-temperature PCR (Polymerase Chain Reaction) and pyrophosphoric acid detection, and provides suggestions from the gene perspective for clinical personalized medication.

The invention relates to the field of drugs, particularly a polypeptide capable of inhibiting tumor necrosis factor and preventing and treating rheumatoid arthritis. The sequence is RINDISHTQSVSSKQKVTG and is a brand-new sequence. The polypeptide can be used for treating rheumatoid arthritis, and has potential new drug development value.

This document provides methods and materials involved in treating autoimmune conditions. For example, methods and materials for using either (a) one or more tumor necrosis factor alpha (TNF-α) inhibitors or (b) one or more Janus kinase (JAK) inhibitors to treat autoimmune conditions such as rheumatoid arthritis are provided.