358 results about "Metalloproteinase" patented technology

The present invention provides methods and compositions comprising at least one neutral metalloprotease enzyme that has improved storage stability. In some embodiments, the neutral metalloprotease finds use in cleaning and other applications. In some particularly preferred embodiments, the present invention provides methods and compositions comprising neutral metalloprotease(s) obtained from Bacillus sp. In some more particularly preferred embodiments, the neutral metalloprotease is obtained from B. amyloliquefaciens. In still further preferred embodiments, the neutral metalloprotease is a variant of the B. amyloliquefaciens neutral metalloprotease. In yet additional embodiments, the neutral metalloprotease is a homolog of the B. amyloliquefaciens neutral metalloprotease. The present invention finds particular use in applications including, but not limited to cleaning, bleaching and disinfecting.

The present invention provides novel polynucleotides encoding Protease-40b polypeptides, fragments and homologues thereof. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to diagnostic and therapeutic methods for applying these novel Protease-40b polypeptides to the diagnosis, treatment, and / or prevention of various diseases and / or disorders related to these polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention.

The present methods and compositions are of use for treatment of conditions involving fibrosis, such as Peyronie's disease plaque, penile corporal fibrosis, penile veno-occlusive dysfunction, Dupuytren's disease nodules, vaginal fibrosis, clitoral fibrosis, female sexual arousal disorder, abnormal wound healing, keloid formation, general fibrosis of the kidney, bladder, prostate, skin, liver, lung, heart, intestines or any other localized or generalized fibrotic condition, vascular fibrosis, arterial intima hyperplasia, atherosclerosis, arteriosclerosis, restenosis, cardiac hypertrophy, hypertension or any condition characterized by excessive fibroblast or smooth muscle cell proliferation or deposition of collagen and extracellular matrix in the blood vessels and / or heart. In certain embodiments, the compositions may comprise a PDE-4 inhibitor, a PDE-5 inhibitor, a compound that elevates cGMP and / or PKG, a stimulator of guanylyl cyclase and / or PKG, a combination of a compound that elevates cGMP, PKG or NO with an antioxidant that decreases ROS, or a compound that increases MMP activity.

Methods and compositions for reducing fibrosis and cirrhosis are provided in which an effective dose of an admixture of a polysaccharide compound and, for example, a compound selected from the group consisting of antibodies specific to intracellular or cell-surface: (i) beta-PDGF receptors; (ii) synaptophysin; (iii) zvegf3; (iv) CCR1 receptors; (v) connective tissue growth factor; (vi) alpha 1-smooth muscle actin; (vii) matrix metalloproteinases MMP 2 and MMP9; (viii) matrix metalloproteinase inhibitors TIMP1 and TMP2; (ix) integrins; (x) TFG-β1; (xi) endothelin receptor antagonists; and (xii) collagen synthesis and degradation modulating compounds; (xiii) actin synthesis and degradation modulating compounds; and (xiv) tyrosine kinases is administered to an animal in order to treat fibrosis.

This invention relates to certain sugar esters of phytosterols of formula (I). These esters are useful for topical application, and for the treatment of skin condition, including age spots, acne, loss of cellular antioxidants, collagen loss, loss of skin pliability, loss of skin suppleness, skin wrinkles including fine lines, oxidation, damage from radiation, malfunction of matrix metalloproteases, malfunction of tyrosinases, damage from free radicals, damage from UV, dry skin, xerosis, ichthyosis, dandruff, brownish spots, keratoses, melasma, lentigines, liver spots, pigmented spots, dark circles under the eyes, skin pigmentation including darkened skin, blemishes, oily skin, warts, eczema, pruritic skin, psoriasis, inflammatory dermatoses, topical inflammation, disturbed keratinization, skin changes associated with aging, nail or skin requiring cleansers, conditioning or treatment, and hair or scalp requiring shampooing or conditioning, and combinations thereof;Wherein,n=0, 1, 2, or 3; andR=H, —CH2OH, —CH(OH)—CH2OH, —CH(OH)—CH(OH)—CH2OH; andR1=Substituent selected from a sapogenin, steroid, or terpenoid.

It has been determined that metalloprotease cleavage of a myostatin pro peptide results in activation of a latent inactive myostatin to an active form. Accordingly, methods of identifying agents that modulate metalloprotease mediated activation of myostatin are provided, as are agents identified using such methods. Also provided are methods of modulating muscle growth in an organism by increasing or decreasing metalloprotease mediated cleavage of a myostatin pro peptide.

This application is a continuation-in-part of pending U.S. patent application Ser. No. 10 / 065,995 by the authors, filed on Dec. 9, 2002, for a Commercial Process for Isolation and Purification of Glabridin with High Tyrosinase Inhibitory Activity and its Cosmetic Compositions and Methods Of Use. The current invention discloses the use of Glabridin containing Licorice extract (4-90% Glabridin) as metalloprotease and hyaluronidase inhibiting component in cosmetic topical or oral formulations. These extracts and particularly Glabridin, are useful in anti-wrinkle and anti-aging products, providing elasticity, firmness, tone and texture to the skin, ameliorating fine lines and crows feet in under eye preparations, and prevent skin and hair damage due to UV rays, inflammation and itch, diaper rashes in baby products, as massage or toning oils or emulsion for babies.

PCT No. PCT / US96 / 19328 Sec. 371 Date Jun. 29, 1998 Sec. 102(e) Date Jun. 29, 1998 PCT Filed Dec. 5, 1996 PCT Pub. No. WO97 / 20824 PCT Pub. Date Jun. 12, 1997The invention relates to compounds of formula (1) wherein: Z is O or S; V is a divalent radical which together with C* and N forms a ring having six ring atoms, where each of said ring atoms other than C* and N independently is unsubstituted or substituted by a suitable substituent, and at least one of said other ring atoms is a heteroatom selected from O, N and S, and the remainder is carbon atoms; and Ar is an aryl or heteroaryl group; and pharmaceutically acceptable prodrugs, salts and solvates thereof. The invention further relates to pharmaceutically acceptable prodrugs, salts and solvates of these compounds. The invention also relates to methods of inhibiting the activity of metalloproteinases by administering a compound of formula (1) or a prodrug, salt or solvate thereof. The invention further relates to pharmaceutical compositions comprising an effective amount of these compounds, prodrugs, salts, and solvates. The invention still further relates to methods and intermediates useful for preparing these compounds, prodrugs, salts, and solvates.

The invention discloses a bacillus subtilis strain capable of efficiently expressing an exogenous secretory proteinase. A bacillus subtilis host bacteria capable of expressing exogenous protein is disclosed. A gene apr of a bacillus subtilis alkaline protease, and a gene npr and a spore forming gene spoIIAC of a bacillus subtilis neutral metalloproteinase are knocked out, wherein the bacillus subtilis alkaline protease and the bacillus subtilis neutral metalloproteinase are two exocrine proteinases in the bacillus subtilis host bacteria. The obtained bacillus subtilis host bacteria can be used for high-yield exogenous proteinases by genetic engineering manners. Based on this, a genetically engineered bacterium secreting pullulanase is constructed and can produce the pullulanase with a high yield. The genetically engineered bacterium secreting has a wide development prospect in industrial production by fermentation industry research.

A dressing for wounds (10) contains a useful material (40), such as dye or biocide, trapped within or behind a gelatin barrier (36). On application to a wound, metalloproteinases naturally present in the wound diffuse into the dressing and degrade the gelatin, releasing the trapped material. The released material serves various useful purposes, such as indicating the status of the wound or improving wound healing.

Formulations and methods useful to reduce ocular neovascularization (new blood vessels in the cornea, retina, conjunctiva, and / or choroid) are disclosed. According to the invention the formulation will include tetracycline or a derivative thereof including chemically modified tetracyclines (CMT) which inhibit matrix metalloproteinase (MMP) activity at a substantially neutral pH in a pharmaceutically acceptable form suitable for delivery to the eye in an amount and for a duration sufficient to reduce ocular neovascularization. According to the invention the formulations are preferably in pharmaceutically acceptable formulations for topical ocular application, ocular injection, or ocular implantation, and may be contained in liposomes or slow release capsules.

The present invention provides compounds of the formula I: its enantiomers, diastereomers, racemic mixtures thereof, prodrugs, crystalline forms, non-crystalline forms, amorphous forms thereof, solvates thereof, metabolites thereof, and pharmaceutically acceptable salts, wherein the ring A substituent groups are fully defined in the following disclosure. The compounds of formula I are inhibitors of metalloproteases such as matrix metalloproteases and sheddases, and are useful in treating diseases such as rheumatoid arthritis, psoriasis, neoplastic diseases, allergies and all those diseases wherein inhibition of MMPs is desirable.

The invention discloses a bacillus licheniformis host bacterium BL10 with multiple gene deletion, the accession number of which is CCTCCNO:M2013400. The host bacterium derives from a bacillus licheniformis WX-02 which partially or completely has deletion of ten genes. The ten genes comprises eight protease genes (mpr encoding a metalloprotease; vpr encoding a serine protease; aprX encoding an intracellular serine protease; epr encoding a minimal extracellular protease; bpr encoding a bacillus peptidase F; wprA encoding a protease combined with cell walls; aprE encoding an extracellular alkaline serine protease; and bprA encoding a bacillus peptidase F) and two extracellular secretory protein genes (hag encoding flagellin; and amyL encoding alpha-amylase). The BL10 has completely no extracellular protease activity and can reduce the degradation effect of a protease on a target protein. When the target protein is expressed by the expression host, the expression level is higher, and the host bacterium benefits protein expression enhancement.

The invention relates to a pyrimidine-4,6-dicarboxylic acid diamide compound, pharmaceutical preparation comprising it, process for preparing it and method for its pharmaceutical use. Particularly, the pyrimidine-4,6-dicarboxylic acid diamide compound is useful for selectively inhibiting collagenase matrix metalloproteinase (MMP) 13, or for treating a degenerative joint disease.

The invention provides a variety of reagents for use in the diagnosis and management of cancer, particularly breast cancer. cDNA microarray technology was used to identify genes whose expression profile across a large group of tumor samples correlates with that of cytokeratin 5 and cytokeratin 17, markers for basal cells of the normal mammary lactation gland. The invention demonstrates that tumors that express cytokeratin 5 / 6 and / or 17 have a poor prognosis relative to tumors overall. The invention provides basal marker genes and their expression products and uses of these genes for diagnosis of cancer and for identification of therapies for cancer. In particular, the invention provides basal marker genes including cadherin3, matrix metalloproteinase 14, and cadherin EGF LAG seven-pass G-type receptor 2. The invention provides antibodies to the polypeptides expressed by these genes and methods of use thereof.

A conjugate comprising a dendritic polymer or other scaffold, a metalloproteinase-cleavable linker and alpha-amanitin. Methods of using this conjugate for safe targeted treatment of cancer cells expressing metalloproteinases.

The invention is a pyrrol alkyl matrix metalloproteinase inhibitor and preparing method, relating to the corresponding compound preparation, active test of inhibiting matrix metalloproteinase and the drug combination in which it acts as active component.

The invention concerns a peptide extract of lupine (lupinus) characterised in that it has a metalloprotease inhibiting activity, in particular collagenase and gelatinase. The invention also concerns a pharmaceutical, cosmetic or nutritional composition comprising a peptide extract, optionally an inert carrier, in particular for treating humans or mammals suffering from a condition or disease related to excessive degeneration of support by a metalloprotease.

The present invention is related to:(i) matrix metalloproteinase inhibitors containing sulfonylamino acid derivatives of the formula (Ia); wherein R1 is hydrogen, C1-4 alkyl; R2 is hydrogen, C1-8 alkyl etc.; E is -CONR3-, in which R3 is hydrogen, C1-4 alkyl etc., -NR3CO-, -CO-O-, -O-CO- etc.; A is hydrogen, C1-8 alkyl, C3-7 cycloalkyl, or Ar; J is bond, C2-4 alkylene etc.; G is -(CH2)m-, in which m is 2, 3 or 4, orin which R6 and R7 is hydrogen, C1-8 alkyl etc.; and non-toxic salts thereof,(ii) sulfonylamino acid derivatives of the formula (Ib):wherein all the symbols are the same meaning as (i); and non-toxic salts thereof, and(iii) process for the preparation of the compound of the formula (Ib).The compounds of the formula (Ia) are useful for prevention and / or treatment of diseases induced by overexpression and excess activity of MMP. The diseases such as above, for example, are rheumatoid, arthrosteitis, unusual bone resorption, osteoporosis, periodontitis, interstitial nephritis, arteriosclerosis, pulmonary emphysema, cirrhosis, cornea injury, metastasis of, invasion of or growth of tumor cell, autoimmune disease (Crohn's disease, Sjogren's syndrome etc.), disease caused by vascular emigration or infiltration of leukocytes, arterialization.

A method for preventing skin-cellular aging by using a green algae extract and a cosmetic composition containing the green algae extract are disclosed. An effective dose of the green algae extract is used to inhibit the activity of Metalloproteinase (MMP) in the fibroblast and to promote of collagens and elastins production in the fibroblast. The green algae extract can be mixed with a skin permeable cosmetic composition so that the cosmetic composition performs the effect of preventing extrinsic skin aging.

The invention relates to the treatment of viral, bacterial, parasitic, proliferative diseases, neurodegenerative diseases, inflammatory diseases, immunological diseases, transplanted organ rejection, and diseases produced by intoxication with heavy metals. The invention relates to the use of specific metal chelating agents including, furoic acid, 2-thiophenecarboxylic acid and their derivatives, analogs and structurally related chemicals as pharmacological agents that can be used effectively to disrupt and inactivate specific transition metal ion containing zinc finger structural motifs in metalloproteins and specific transition metal ion containing catalytic sites in metalloproteinases, which in turn, inactivate the pathogenic virus, pathogenic prokaryotic or eukaryotic cells which produces disease conditions. The preparations can be administered topically or for systemic use. The preparations are novel wide-spectrum antibiotics which have antiviral, antiproliferative, antineoplastic, antiangiogenic, antibacterial, antiparasitic, antiinfective, and anti-inflammatory effects and can be used in the treatment and prevention of diseases such as AIDS, cancers, untoward angiogenesis, pulmonary anthrax, malaria, inflammatory responses, Alzheimer's disease and other diseases.

The present invention provides compositions and methods useful for regulating fertilization and for use as a contraceptive based on the discovery herein of an oocyte specific protein, SAS1R (Sperm Acrosomal SLLP1 Receptor), which is a sperm protein receptor. Six SAS1R variants, including the full length SAS1R, were identified. mSLLP1 and SAS1R co-localized to oocytes and to acrosomes of acrosome-reacted sperm. Interactions between mSLLP1 and SAS1R were demonstrated by far-western analysis, in a yeast two-hybrid system under stringent selection conditions, and by immunoprecipitation of SAS1R by anti-mSLLP1 as well as the converse. Purified recombinant SAS1R was found to have protease activity, to inhibit fertilization in-vitro, and to induce an immune response in females. Together, the results suggest SAS1R is a proteolytically active, oocyte and early embryo specific oolemmal metalloprotease receptor for the sperm intra-acrosomal ligand SLLP1 and is a target for regulating fertilization and as a contraceptive.

Methods and apparatus provide for treating and / or preventing tumor growth and / or spread, and / or other conditions in which Matrix Metalloproteinase (MMP) protein has been implicated in a patient, comprising: generating at least one specific and selective electric signal that when applied to electrodes, one or more coils, or other field generating devices operatively disposed with respect to targeted tissue causes the generation of a specific and selective electric field in the targeted tissue that substantially down-regulates the gene expression of MMP protein in said targeted tissue as measured by mRNA production; and exposing said targeted tissue to the specific and selective electric field generated by said electrodes, one or more coils, or other field generating devices upon application of said at least one specific and selective electric signal thereto for a duration of between about 3-5 hours at predetermined intervals so as to selectively down-regulate the gene expression of MMP protein in said targeted tissue as measured by mRNA production.

Disclosed herein are methods of and systems for predicting recurrence of atrial fibrillation comprising protease and protease inhibitor profiling. The levels of matrix metalloproteinases (MMPs) and / or tissue inhibitor metalloproteinases (TIMPs) are analyzed to predict the recurrence of atrial fibrillation, and further to predict whether cardioversion will provide a successful therapy.

The present invention relates to cleaning and / or detergent compositions comprising metalloproteases (E.C 3.4.24). The invention further concerns the use of the metalloproteases in cleaning processes, such as dish wash and laundry, and in particular to the use in low temperature wash and in removal of egg stains. Further the invention concerns methods of doing cleaning, such as dish wash and laundry.

The invention relates to an enzymatic test kit for glycosylated hemoglobin, which is composed of hemolysis buffer solution, reagent R1a, reagent R1b and reagent 2; wherein, the hemolysis buffer solution is 10 to 1000mmol / L N- cycloethyl-2-aminoethanesulfonic acid, 10 to 1000mmol / L MOPS and 1 to 100g / L polyethylene glycol oxide dodecyl ether; the reagent R1a is 100 to 10000 kU / L metalloproteinase, 0.1 to 10mmol / L 2-(iodophenyl)-3-(2, 4- dinitrobenzene)-5-(2, 4-disulfophenyl)-2H tetrazole sodium salt; the reagent R1b is 0.1 to 10mmol / L MES and 0.5 to 50mmol / L CaCl2; the reagent 2 is 1 to 100kU / L fructose valine oxidase with high activity, 30 to 600kU / L POD, 0.01 to 0.5mmol / L DA-64 and 10 to 1000mmol / L Tris-HCl. The test kit coincides with the characteristics of rapidness, large batch size and economy which are required by the glycosylated hemoglobin clinical tests.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using assays that detect one or more markers selected from the group consisting of Clusterin, Heart-type fatty acid binding protein, Hepatocyte growth factor, Interferon gamma, Interleukin-12 subunit beta, Interleukin-16, Interleukin-2, 72 kDa type IV collagenase, Matrix metalloproteinase-9, Midkine, and Serum amyloid P-component as diagnostic and prognostic biomarkers in renal injuries.

Invasive remodelling in a mammal may be inhibited by (1) inhibiting or abolishing the protein cleaving action of plasmin and (2) inhibiting or abolishing the protein cleaving action of at least one additional proteolytic enzyme active in invasive remodelling, such as a metalloprotease.

The invention discloses a matrix metalloproteinase-2 specific multi-modality molecular image probe preparation method and application thereof. The preparation method comprises the following steps: 1)preparing peptide substrates for matrix metalloproteinase-2(MMP-2) specific identification; 2) modifying near infrared fluorescent dye on peptide substrate; 3) modifying fluorescent quenching group onpeptide substrate; 4) connecting different molecular weight PEG or tumor targeting group RGD on peptide substrate modified with near infrared fluorescent dye and fluorescent quenching group; 5) labeling the nuclide on the above modified peptide substrate side chain tyrosine. Compared with the prior art, the matrix metalloproteinase-2 specific multi-modality molecular image probe preparation method has the advantages that: 1) by utilizing the specificity and responsiveness of the MMP-2 protease by the probe, so that the probe is selectively enriched at the tumor site so as to improve the targeting property of the probe to the tumor; 2) performing multi-modality imaging in a living body tumor by using advanced molecular imaging technology such as optical, opto-acoustic, SPECT and the like,improving the sensitivity and accuracy of tumor imaging, and finally achieving accurate positioning of the tumor; 3) providing a new train of thought and method for early diagnosis, process research and prognosis evaluation of tumor.