192 results about "Tumor necrosis factor alpha" patented technology

Methods and compositions for the prevention and treatment of all forms of atherosclerosis are described. Administration of compounds such as thalidomide, its analogs, hydrolysis products, metabolites, derivatives and precursors as well as additional compounds capable of inhibiting tumor necrosis factor alpha (TNF-alpha) are used in the invention. Also disclosed is the coating of prosthetic devices, such as stents, with the compounds of the invention for the prevention and / or treatment of restenosis.

Substances comprising disaccharides and substances comprising carboxylated and / or sulfated oligosaccharides in substantially purified form, and methods of using same, are disclosed for the regulation of cytokine activity in a host. For instance, the secretion of active Tumor Necrosis Factor Alpha (TNF- alpha ) can be either inhibited or augmented selectively by administration to the host of an effective amount of a substance of the invention. Thus, the present invention also relates to pharmaceutical compositions and their use for the prevention and / or treatment of pathological processes involving the induction of active cytokine secretion, such as TNF- alpha . The invention also relates to the initiation of a desirable immune system-related response by the host to the presence of activators, including pathogens. The substances and pharmaceutical compositions of the present invention may be administered daily, at very low effective doses, typically below 0.1 mg / kg human, or at intervals of up to about 5-8 days, preferably once a week.

The invention features a series of heterocyclic derivatives that inhibit tumor necrosis factor alpha (TNF-α) induced necroptosis. The heterocyclic compounds of the invention are described by Formulas (I) and (Ia)-(Ie) and are shown to inhibit TNF-α induced necroptosis in FADD-deficient variant of human Jurkat T cells. The invention further features pharmaceutical compositions featuring the compounds of the invention. The compounds and compositions of the invention may also be used to treat disorders where necroptosis is likely to play a substantial role.

The invention features a series of heterocyclic derivatives that inhibit tumor necrosis factor alpha (TNF-α) induced necroptosis. The heterocyclic compounds of the invention are described by Formulas (I)-(VIII) and by Compounds (1)-(7), (13)-(26), (27)-(33), (48)-(57), and (58)-(70). These necrostatins are shown to inhibit TNF-α induced necroptosis in FADD-deficient variant of human Jurkat T cells. The invention further features pharmaceutical compositions featuring necrostatins. The compounds and compositions of the invention may also be used to treat disorders where necroptosis is likely to play a substantial role.

A method for treating skin, reducing oxidative damage to a skin cell, reducing lipoxygenase (LO) activity in a skin cell, reducing cyclooxygenase (COX) activity in a skin cell, reducing tumor necrosis factor alpha (TNF-α) in a skin cell, or reduction matrix metalloproteinase enzyme activity in a skin cell comprising contacting skin or a skin cell with an aromatic skin-active ingredient.

The invention features a series of heterocyclic derivatives that inhibit tumor necrosis factor alpha (TNF-α) induced necroptosis. The heterocyclic compounds of the invention are described by Formulas (I) and (Ia)-(Ie) and are shown to inhibit TNF-α induced necroptosis in FADD-deficient variant of human Jurkat T cells. The invention further features pharmaceutical compositions featuring the compounds of the invention. The compounds and compositions of the invention may also be used to treat disorders where necroptosis is likely to play a substantial role.

The present invention provides compounds of structural formula (I), which are agonists of formyl peptide receptor (FPR), particularly formyl peptide receptor like 1 (FPRL1). The present invention also provides the therapeutic use of the compounds of formula (I).

The invention discloses a compound probiotic agent for improving immunity of dogs and reducing incidence of diarrhea as well as a preparation method and application thereof, and belongs to the field of the compound probiotic agent. The compound probiotic agent is prepared by mixing and compounding a lactobacillus plantarum KT-Lp9 microbial agent, a lactobacillus casei zhang microbial agent, a lactobacillus plantarum P-8 microbial agent, a bifidobacterium animalis subsp. lactis V9 microbial agent and a dilution carrier, wherein the quantity of viable bacteria of the four kinds of microbial agents is more than or equal to 2*10<11>CFU / g. The compound probiotic agent with different contents of viable bacteria only can be applied to 96 dogs at different ages for 60 days, so that the immunity of the test dogs can be improved, and the incidence of diarrhea and the sickness degree are reduced. Main representations are that the feed intake and growth rate of the dogs are increased, leukocyte counts, lymphocytes counts and neutrophil counts in blood are controlled, and the contents of four immunologic factors including immune globulin G, interleukin 6, interferon alpha and tumor necrosis factor alpha in the blood can be increased; and meanwhile, the content of secretory immunoglobulin A (SigA) in excrement is increased.

The invention belongs to the field of pharmacy, and relates to application of a hydrogen sulfide donor to the preparation of a medicine for treating central nervous system disease, in particular to application of the hydrogen sulfide donor, namely sodium hydrosulfide, or allyl cysteine and analogues thereof to the preparation of the medicine for treating the central nervous system disease. Integral animal model experiments prove that the sodium hydrosulfide and propargyl cysteine can reduce the learning and memory impairment of rats, increase the content of hydrogen sulfide in hippocampus tissues of the rats, inhibit the messenger ribonucleic acid (mRNA) expression of a tumor necrosis factor alpha and a receptor I thereof, inhibit an inflammatory mediator in the hippocampus tissues of rats with dementia and inhibit inflammation-related enzymes in the hippocampus tissues of the rats, and can be used as a medicine for treating Alzheimer disease and other inflammation-related central nervous system degenerative diseases such as Parkinson disease.

Described herein are antibodies that bind to human tumor necrosis factor alpha (hTNFα). And list the nucleotide sequence of antibody heavy chain and light chain variable region and its derived amino acid sequence. The heavy chain and light chain variable region genes are respectively connected with the human immunoglobulin gamma 1 (hIgG1) heavy chain constant region and human kappa (k) light chain constant region genes to form a chimeric gene. Then, the vector containing the chimeric gene is introduced into the host cell line to express the antibody protein. This recombinant chimeric antibody protein can neutralize the activity of hTNFα in vitro, and is suitable for treating patients with excessive secretion of harmful hTNFα, including certain inflammations, such as rheumatoid arthritis and Crohn's disease.

The invention provides an anti-tumor necrosis factor human-derived monoclonal antibody and application of the human-derived monoclonal antibody. Compared with the traditional mouse chimeric antibody, the anti-tumor necrosis factor human-derived monoclonal antibody has the advantages that the antigen identifying capability of the antibody is kept, and the immunogenicity of mouse-derived antibody is greatly reduced, so that the clinical application security of the antibody is improved.

The invention relates to a design technology for fusion protein and a protein expression and purification technology, and relates the application of fusion protein as a tumor therapeutic medicament. The invention is characterized by fusing the 114th-281th amino acid of tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) with human IgGlFc. The fused protein consists of 400 amino acids, the isoelectric point pI is 9.34, and theoretical molecular weight is 45535.30. The protein exists by a dimer or a trimer, can remarkably induce apoptosis of a plurality of kinds of tumor cellsand kills or / and inhibit tumor cells in an animal body. Compared with TRAIL, the TRAIL-Fc fusion protein has large molecular weight, high activity and long vivo half-life, is expressed by mammalian cells, and can be used as a tumor therapeutic medicament.

A prerequisite of proteomics is the ability to quantify many selected proteins simultaneously. Fluorescent sandwich immunoassays on microarrays hold appeal for such studies, since equipment and antibodies are readily available, and assays are simple, scalable and reproducible. To attain adequate sensitivity and specificity, however, a general method of immunoassay amplification is required. Coupling of isothermal rolling circle amplification (RCA) to universal antibodies can be used for this purpose: RCA on a synthetic DNA circle is initiated by a complementary oligonucleotide attached to an anti-biotin antibody; single-stranded RCA product remains attached to the antibody, and is detected by hybridization of complementary, fluorescent oligonucleotides. 51 cytokines were measured simultaneously on microarrays with signal amplification by RCA with high specificity, femtomolar sensitivity and 4 log quantitative range. This cytokine microarray was used to measure secretion from human Dendritic cells (DCs) induced by lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-(alpha). Rapid secretion of inflammatory cytokines such as MIP-1beta, IL-8, and IP-10 was induced by LPS. Eotaxin-2 and I-309 were found to be induced by LPS, and MDC, TARC, sIL-6R, and sTNF-RI were found to be induced by TNF-alpha. Since microarrays can accommodate ~1000 sandwich immunoassays of this type, a relatively small number of RCA microarrays appears to offer a tractable approach for proteomic surveys.

The present invention relates to amino acid sequences, compounds and polypeptides binding to tumor necrosis factor alpha (“TNF” or “TNF-alpha”). In particular, the present invention relates to improved heavy-chain immunoglobulin single variable domains (also referred to herein as “ISV's” or “ISVDs”) binding to tumor necrosis factor alpha, as well as to proteins, polypeptides and other constructs, compounds, molecules or chemical entities that comprise such ISVDs, collectively TNF binders. Other aspects, embodiments, features, uses and advantages of the invention will be clear to the skilled person based on the disclosure herein.

Imidazole and benzimidazole boronic acid compounds, analogs thereof, and pharmaceutical formulations are described, along with methods of use thereof for inhibiting inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) in a subject in need thereof.

The invention relates to matrix metallic protease-directed recombination human tumor necrosis factor fused protein and a method for making the same. The amino acid sequence of the fused protein consists of three parts, i.e. a collagen sequence, a (a sort or a class of) human matrix metallic protease substrate sequence and a human tumor necrosis factor-alpha sequence (as shown in graph 1) which are arranged in turn from an N-end. When tumor necrosis factor-alpha is formed into a trimerical active form, the collagen sequence is formed into right hand triple helix, and plays a role in closing the recipient binding site of tumor necrosis factor-alpha along with the human matrix metallic protease substrate sequence. The specific cutting of the fused protein can be completed by matrix metallic protease excreted by a tumor tissue inside the tumor tissue so as to expose the recipient binding site of tumor necrosis factor-alpha and to represent cytotoxic activity; however, the fused protein does not represent cytotoxic activity in most normal tissues. The fused protein has tumor-targeting characteristics and the action of killing tumor cells, thereby having enormous application prospect in curing tumor.

Novel imides are inhibitors of tumor necrosis factor alpha and can be used to combat cachexia, endotoxic shock, and retrovirus replication. A typical embodiment is (R)-2-Phthalimido-3-(3′,4′-dimethoxyphenyl)propane.

treatment of a variety of disorders, including the treatment of pathological conditions associated with tumor necrosis factor alpha. The inhibitors of tumor necrosis factor alpha have the following structures:including stereoisomers, pharmaceutically acceptable salts, and solvates thereof, wherein substituents are as defined herein. Compositions containing an inhibitor of tumor necrosis factor alpha in combination with a pharmaceutically acceptable carrier are also provided, as well as methods for use of the same.

Drug compositions for treatment of one or more inflammatory conditions can includes at least one of a θ-defensin, analog or derivative thereof. Inventive methods include researching θ-defensins, analogs or derivatives thereof for their efficacy with respect to anti-inflammatory effects, and providing such compositions to the marketplace for the purpose of treating inflammatory conditions. Of particular interest are drug compositions effective to produce clinically relevant inhibition of tumor necrosis factor alpha (TNF-α)-converting enzyme (TACE) or other proinflammatory proteases, and / or sheddases. it is contemplated that preferred compositions can be used to treat rheumatoid arthritis, inflammatory bowel disease, and other chronic inflammatory diseases, autoimmune diseases, cancer, and Alzheimer's, osteoarthritis, inflammation-related neurodegenerative and other inflammation-related diseases.

The invention provides a preparation method of a large-scale culture dendritic cell vaccine. The preparation method comprises the following process steps of: performing in-vitro separation and purification on collected white blood cells in human peripheral blood by adopting a blood cell separation machine to obtain a large number of mononuclear cells, wherein the order of magnitude can be above 10<9>; using a human granulocyte-macrophage colony stimulating factor and interleukin 4 to induce the culture to obtain a large number of immature dendritic cells, wherein the order of magnitude can be above 10<8>; and loading a tumor specific antigen in the immature dendritic cells, and then obtaining the mature dendritic cell vaccine with an anti-tumor effect under the induction culture conditions of a tumor necrosis factor alpha and lipopolysaccharides. The invention further provides a multi-time and multi-treatment course clinical application of the dendritic cell vaccine obtained through the method.

Improved methods for treating neoplastic diseases such as cancer are provided by using muteins of human tumor necrosis factor-alpha (TNF-alpha). Compared to wild-type human TNF-alpha these therapeutic TNF muteins have higher specific anti-tumor activity, but with much reduced systemic toxicity and milder side effects such chills and fever. In addition, potentially synergistic, novel combinations of the inventive TNF-alpha muteins with other anti-neoplastic agents are provided for effectively treating patients having particular types of cancer or malignancy or at particular stages of cancer development.

The present invention is based on the finding that peptides derived from a specific domain of tumor necrosis factor-alpha (TNF-alpha) can efficiently be used to treat oedema. More specifically, the present invention relates to the usage of peptides derived from the region of human TNF-alpha from Ser<100 >to Glu<116 >to treat pulmonary oedema. For example, the circularized peptide having amino acid sequence CGQRETPEGAEAKPWYC is shown to be very efficient in inducing oedema resorption.

A new protein, named ACA1, has been isolated and purified from the medical fungi Antrodia camphorata using the technique of anion-exchange chromatography. ACA1, a glycoprotein with a molecular mass of 29 kDa, has a pI value of pH 5.3 and contains 118 amino acids in its peptide moiety. In addition, ACA1 contains methionine, half-cystine and histidine residues, which are not existent in FIP-fve and Ling Zhi-8. ACA1 is not able to agglutinate red blood cells from human and mouse. Moreover, ACA1 possesses immunomodulatory activities, which are demonstrated by their stimulatory activity toward RAW 264.7 macrophages and mouse splenocytes. ACA1 can directly enhance the production of tumor necrosis factor-alpha and nitric oxide by RAW 264.7 macrophages, and induce cell proliferation and interferon-gamma secretion by mouse splenocytes.

The invention provides a liquid protein chip kit for detecting a liver fibrosis degree. In the liquid protein chip kit, coupling antibody microspheres comprise 1, fluorescent microspheres coupling with procollagen peptide III and / or a metalloprotease tissue inhibitor factor-1 capture antibody, 2, one or more of fluorescent microspheres coupling with collagen peptide IV, fibronectin, a transforming growth factor-beta 1, a platelet-derived growth factor, a tumor necrosis factor alpha capture antibody, and an angiotensin II capture antibody, and 3, fluorescent microspheres coupling with a serum hyaluronic acid capture antibody and / or a laminin capture antibody. The liquid protein chip kit can realize combined detection of a plurality of liver fibrosis-related markers for reflection of different liver fibrosis stages, can shorten detection time to more than ten minutes from a few hours, can finish detection of a plurality of markers only by 1 microliter of a serum sample, can be operated simply and has a low diagnosis cost.

The invention discloses an antibody combined with human tumor necrosis factor Alpha (hTNF a), juxtaposing out antibody heavy chain and nucleotide sequence of light chain variable region, and the amino acid sequence derived from the nucleotide sequence. The heavy chain and the light china are connected into chimeric genes with the genes in the human immunoglobulin gamma 1(hIgG1) heavy china constant region and in the kappa (k) light chain constant region respectively, then the carrier with the chimeric genes is introduced into the host cell line expressing antibodies protein. The restructuringchimeric antibody protein is tested outside human body and can neutralize the hTNF Alpha activity. The invention is suitable for treating disease of excessive harmful hTNF Alpha secretion, comprisinga plurality of inflammations such as rheumatoid arthritis and regional enteritis.

The invention is a method of treatment of the symptoms related to inflammation that accompanies the release of Tumor Necrosis Factor-alpha in diseases such as viral infection such as those affecting the respiratory tract by providing systemic glutathione (reduced) by oral administration of glutathione (reduced) in a liposome encapsulation or by the intravenous administration of reduced glutathione. The administration of a therapeutically effective amount of oral liposomal glutathione (reduced) results in improvement of symptoms of disease induced by the release of TNF-α in infectious disease states such as respiratory and other viruses. The product is novel in that it is stable across the temperature ranges encountered in shipping and does not need to be refrigerated for storage. Compounds enhancing the effect of the liposomal glutathione as well as intravenous glutathione are contemplated such as Selenium.

The invention discloses application of sinomenine derivatives in the treatment of autoimmune diseases by antagonizing a TNF-alpha signaling pathway, namely application of the sinomenine derivatives shown in a formula I, wherein the sinomenine derivatives can be used for preparing a composition for preventing or treating the autoimmune diseases. The invention also discloses application of a compound shown in the formula I in preparation of a tumor necrosis factor-alpha (TNF-alpha) signaling pathway inhibitor composition.