108 results about "Human neutrophil" patented technology

α-MSH and other amino acid sequences derived from α-MSH were determined to have antimicrobial influences, including against two major and representative cutaneous and mucosal pathogens; Staphylococcus aureus and Candida albicans, Pharmaceutical compositions useful as antimicrobial agents, including for use in reducing the viability of microbes, reducing the germination of yeasts, killing microbes without reducing the killing of microbes by human neutrophils, for treating inflammation in which there is microbial infection without reducing microbial killing, and for increasing the accumulation of cAMP in microbes are disclosed. The antimicrobial agent is selected from the group consisting of one or more peptides including the amino acid sequence KPV, one or more peptides including the amino acid sequence MEHFRWG, or a biologically functional equivalent of any of the foregoing. The most effective of the peprides were those bearing the C-terminal amino acid sequence of α-MSH. i.e., α-MSH (1-13), (6-13), and (11-13).

The invention relates to a Kunitz domain peptide, designated DPI-14 herein, for inhibiting human neutrophil elastase. The invention also relates to a method of using a DPI-14 for treating cystic fibrosis or cystic fibrosis-related disease or disorder.

Methods for diagnosing renal disorders by measuring human neutrophil gelatinase-associated lipocalin (NGAL) are provided.

The invention provides compounds of formula

wherein R¹, R³, R⁴, R⁵, R⁶, R⁷, L, X and Y are as defined in the specification; together with processes and intermediates for their preparation, pharmaceutical compositions containing them and their use in therapy. The compounds are inhibitors of human neutrophil elastase.

Compounds of formula (I):

are useful as inhibitors of human neutrophil elastase.

Compounds of formula (I) and multimers thereof are inhibitors of human neutrophil elastase activity, and of utility in the treatment of, e.g., COPD:

wherein A is aryl or heteroaryl; D is oxygen or sulphur; R¹, R² and R³ are independently each hydrogen, halogen, nitro, cyano, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, hydroxy or C₁-C₆-alkoxy or C₂-C₆-alkenyloxy, wherein C₁-C₆-alkyl and C₁-C₆-alkoxy can be further substituted with one to three identical or different radicals selected from the group consisting of halogen, hydroxy and C₁-C₄-alkoxy;

R and R⁴ each independently represent a radical of formula

—[X]_m-[Alk¹]_p-[Q]_n-[Alk²]_q-[X¹]_k-Z wherein k, m, n, p and q are independently 0 or 1; Alk¹ and Alk² each independently represent an optionally substituted C₁-C₆ alkylene, or C₂-C₆ alkenylene radical which may optionally contain an ether (O—), thioether (—S—) or amino (—NR^A—) link wherein R^A is hydrogen or C₁-C₃ alkyl; Q represents (i) O—, —S—, —S(═O)—, —S(═O)₂—, —S⁺(R^A)—, —N(R^A)—, —N⁺(R^A)(R^B)—, —C(═O)—, —C(═O)O—, —OC(═O)—, —C(═O)NR^A—, —NR^AC(═O)—, —S(O₂)NR^A—, —NR^AS(O₂)—, —NR^AC(═O)NR^B—, —NR^AC(═NR^A)NR^B—, —C(═NR^D)NR^E, —NR^EC(═NR^D), wherein R^A, R^B, R^D and R^E are independently hydrogen, C₁-C₆ alkyl, or C₃-C₆ cycloalkyl, or R^A and R^B, or R^D and R^E taken together with the nitrogen to which they are attached form a monocyclic heterocyclic ring of 5 to 7 ring atoms which my contain a further heteroatom selected from N, O and S, or (ii) an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 3-6 ring members; X represents —(C═O)—, —S(O₂)—, —C(═O)O—, —(C═O)NR^A—, or —S(O₂)NR^A—, wherein R^A is hydrogen, C₁-C₆ alkyl, or C₃-C₆ cycloalkyl; X¹ represents —O—, —S—, or —NH; and Z is hydrogen or an optionally substituted mono- or bicyclic carbocyclic or heterocyclic radical having 3-6 ring members.

The invention provides compounds of formula wherein R¹, R³, R⁴, R⁵, R⁶, R¹⁴, X, W and Z are as defined in the specification and optical isomers, racemates and tautomers thereof, and pharmaceutically acceptable salts thereof; together with processes for their preparation, pharmaceutical compositions containing them and their use in therapy. The compounds are inhibitors of human neutrophil elastase.

Compounds of formula (I) defined herein exhibit human neutrophil elastase inhibitory properties and are useful for treating diseases and conditions in which HNE is implicated.

The invention provides compounds of formula

wherein R¹, R³, R⁴, R⁵, R¹⁴, X and W are as defined in the specification and optical isomers, racemates and tautomers thereof, and pharmaceutically acceptable salts thereof; together with processes for their preparation, pharmaceutical compositions containing them and their use in therapy. The compounds are inhibitors of human neutrophil elastase.

The subject invention is related to human MMP-8alt genes and gene products and their differential expression when comparing a patient with a disease state to a control. A further aspect of the invention concerns compounds which antagonize the biological activity of MMP-8alt protein and methods for identifying these compounds. Another aspect of the present invention concerns pharmaceutical compositions comprising such compounds for the treatment of arthritis, cancer, and disease caused by cellular apoptosis including but not limited to Parkinson's disease, Alzheimer's disease and Huntington's chorea.

The invention discloses a hybridoma cell strain 3B1 and a hybridoma cell strain 4C2 and a mouse anti-human NGAL monoclonal antibody 3B1 and a mouse anti-human NGAL monoclonal antibody4C2 produced respectively. The two kinds of monoclonal antibodies belong to a same immunoglobulin G (IgG) 2a subclass, but identify various epitopes and can perform specific binding to NGAL recombinant protein with amino acid sequences represented by SEQ ID NO.1. The two monoclonal antibodies can be applied to detect the concentration of the NGAL in human body fluids and have significant application prospect.

The invention discloses a neutrophil gelatinase-associated lipocalin determination kit. The kit comprises a reagent R1 and a reagent R2 which are liquid components and are mutually independent, the reagent R1 comprises a buffer solution, inorganic salt ions, an accelerator, a chelating agent, a stabilizer, an antiseptic and an anti-humanr heumatoid factor antibody, and the reagent R2 comprises the buffer solution, the stabilizer, a suspending aid, a surfactant, the antiseptic and a latex coated anti-human neutrophil gelatinase-associated lipocalin. The preparation method comprises the following steps: preparing the reagents according to the component content; mixing a sample to be determined with the reagent R1 and the reagent R2 to fully react the sample to be determined with the reagent R1 and the reagent R2; determining the absorbance difference by using a fully-automatic biochemical analyzer after the reaction; and calculating the concentration of neutrophil gelatinase-associated lipocalin in the sample according to the absorbance change value. The kit has high accuracy.

The present invention provides compositions useful as antimicrobial agents which include mammalian hemoglobin, the alpha and beta chains of hemoglobin free of heme, fragments of the alpha and beta chains that result from cyanogen bromide cleavage of the alpha and beta chains, and synthetic peptides derived therefrom. The compositions exert antimicrobial activity against both bacteria and fungi that is comparable to known antimicrobial peptides from human neutrophils, cathepsin G and azurocidin. Sensitive organisms include Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa, Gram-positive bacteria such as Staphylococcus aureus and Streptococcus faecalis, and the fungus Candida albicans. Methods for preparing the compositions also are provided.

The invention belongs to the medical field and particularly relates to an acute kidney injury diagnosis technology, a B cell epitope peptide of human NGAL (Neutrophil Gelatinase Associated Lipocalin) and a hybridoma cell prepared by same, and an application of the B cell epitope peptide and a specific antibody thereof and an immune complex of the specific antibody in preparing diagnostic reagent for acute kidney injury. The B cell epitope peptide prepared by the invention immunizes a monoclonal antibody prepared by adopting a rat and has the advantages of high purity (The SDS (Sodium Dodecyl Sulfate)-PAGE (PolyAcrylamide Gel Electrophoresi) detection purity is more than 96 percent), high valence (the ELISA (Enzyme-Linked Immuno Sorbent Assay) valence reaches 1:256000), good specificity, mass preparation and the like; and through the monoclonal antibody and a polyclonal antibody prepared by the B cell epitope peptide, the B cell epitope peptide can be used for detecting the content of the NGAL in the urine of a patient, for example, by adopting a double antibody sandwich ELISA reaction mode, a double antibody sandwich structure formed by an enzyme labeled human anti-NGAL monoclonal antibody, an enzyme labeled plate package anti-NGAL polyclonal antibody and a measured sample NGAL antigen is detected.

The invention provides compounds of formula (I) and formula (IV) (M)-(L)-(M) (I) [(M)-(L⁴)]_t-G (VI) wherein M, L, L⁴, G and t are as defined in the specification and optical isomers, racemates and tautomers thereof, and pharmaceutically acceptable salts thereof; together with processes for their preparation, pharmaceutical compositions containing them and their use in therapy. The compounds are inhibitors of human neutrophil elastase.

The invention provides certain novel 6-heteroaryl-5-methyl-3-oxo-4-[3(trifluoromethyl)phenyl]-3,4-dihydropyrazine-2-carboxamide derivatives and pharmaceutically acceptable salts thereof and particular Forms thereof; together with processes for their preparation, pharmaceutical compositions containing them and their use in therapy. The compounds are inhibitors of human neutrophil elastase.

The present invention discloses novel active polypeptide fragments of human IL-33 corresponding to natural forms generated by the proteases of human neutrophils (cathepsin G, elastase 2, proteinase 3), as well as the use thereof as a drug, in particular for the treatment of infectious diseases, inflammatory diseases, atherosclerosis, cardiovascular diseases, obesity, or cancer.

The invention discloses a magnetic nanoparticle immobilized with an anthrax lethal factor on a surface as well as a preparation method of the magnetic nanoparticle and application of the magnetic nanoparticle in enrichment of human neutrophil peptides. The magnetic nanoparticle immobilized with the anthrax lethal factor on the surface is obtained by connecting the anthrax lethal factor to the surface of the superparamagnetic nanoparticle with amino and/or carboxyl on surface by virtue of amino-carboxyl coupling reaction; the magnetic nanoparticle can quickly and specially enrich the human neutrophil peptides for further detection, so that application of the human neutrophil peptides as tumor prognosis biomarkers is convenient, and therefore, clinical application prospect is very good.

Human α-defensins are inhibitors of interleukin-1β post transitional processing and release. Interleukin-1β is a key cytokine involved in the initiation and amplification of the inflammatory process, including the inflammation of diseases such as Crohn's Disease and Ulcerative Colitis. Particularly, human neutrophil defensin-1(HNP-1) produced mainly by neutrophils, and human α-defensin 5(HD-5) produced by Paneth cells has been found to block interleukin-1β post transitional processing and release. Thus, a pharmaceutical composition and method for treating inflammation in the mammalian tissues is herein disclosed. The pharmaceutical composition is a therapeutic supplementation of a metabolic pathway to reduce inflammation comprising a human α-defensins in a therapeutically effective amount or an amide, ester or salt thereof and a pharmaceutically effective carrier. The method for treating inflammation in mammalian tissues includes administering a human α-defensins to a mammal in an amount effective to inhibit the post translational processing and release of interleukin-1β.

Based on recent investigations showing iatrogenic, profound neutropenia (and the fever spikes that often accompany it, which must be medicated immediately to avoid the risk of life-threatening infection) can most accurately be monitored by obtaining daily mucosal neutrophil counts from the patient's oral mucosa rather than obtaining daily counts of the patient's blood neutrophils as in the past, a mouth wash method has been developed for collecting muscosal neutrophils. The mouth wash samples so collected are delivered directly, or in aqueous dilution to a sample pad supported on a strip which sample pad has deposited thereon reagents enabling a colorimetric, fluorescent or chemiluminescent assay of the quantity of an enzyme characteristic of human neutrophils that is present in the sample. This measured quantity can be correlated to mucosal neutrophil count. The method shows outstanding sensitivity, precision and accuracy relative to microscopic methods of counting mucosal neutrophils.

The invention discloses a method for treating septicemia with human neutrophil peptide (HNP) blocking agents. The method comprises the following steps of: preparing small interfering RNA (siRNA) and anti-HNP antibody blocking agents and the like, and blocking, neutralizing and reducing the yield, the function and the biological activity of HNP. The siRNA is prepared in vitro through a design and a chemical synthesis method. A HNP-1 polypeptide is produced through a design to be cross-linked with KLH (Keyhole Limpet Hemocyanin) and then to immunize an experimental rabbit, and a rabbit immune globulin is obtained. The same one HNP-1 polypeptide is used for immunizing a mouse, an anti-HNP antibody variable region is prepared, and then a humanized monoclonal anti-HNP-1 antibody is prepared. Both of the siRNA and the anti-HNP-1 antibody can effectively block, neutralize and reduce the yield, the function and the biological activity of HNP, so that the method can be used for treating septicemia and other related diseases caused by bacterial infections.

The invention relates to anti-human neutrophil gelatinase-associated lipocalin (NGAL) antibodies and a use thereof, and discloses the monoclonal antibodies for specific detection of NGAL and a detection kit containing the monoclonal antibodies. Compared with traditional diagnostic methods and nucleic acid diagnostic methods, the kit not only has the characteristics of fast diagnostic speed, high accuracy degree and high throughput, but also has the characteristics of low cost, simple operation and the like.