130 results about "Matrix metalloproteases" patented technology

The present invention provides for plant extracts and dermatological formulations comprising one or more plant extracts that are capable of inhibiting one or more extracellular proteases selected from the group of: matrix metalloprotease-1 (MMP-1), matrix metalloprotease-2 (MMP-2), matrix metalloprotease-3 (MMP-3), matrix metalloprotease-9 (MMP-9) and human leukocyte elastase (HLE). The present invention further provides for a rapid method for screening plant extracts to identify those having the above activity that are suitable for incorporation into the dermatological formulations of the invention. The invention also provides for the use of the plant extracts as dermatological agents suitable for the treatment or prevention of various dermatological conditions, including wrinkling or sagging of the skin, irradiation induced skin and / or hair damage, deepening of skin lines, elastotic changes in the skin, as well as for the routine care of the skin, hair and / or nails.

A compound selected from those of formula (I): in which: R1 represents a group selected from hydrogen, amino, alkyl, alkenyl, aminoalkyl, aryl, arylalkyl, heterocycle, and cycloalkylalkyl, optionally substituted, W represents oxygen, sulfhur, or =N-R', in which R' is as defined in the description, X1, X2 and X3 represent nitrogen or -C-R6 in which R6 is as defined in the description, Y represents oxygen, sulfhur, -NH, or -N(C1-C6)alkyl, Z represents oxygen, sulfhur, -NR7 in which R7 is as defined in the description, and 59 optionally carbon atom, n is an integer from 1 to 8 inclusive, Z1 represents -CR8R9 wherein R8 and R9 are as defined in the description, A represents aromatic or non-aromatic, heterocyclic or non-heterocyclic ring system, m is an integer from 0 to 7 inclusive, the group(s) R2 is (are) is as defined in the description, R3 represents hydrogen, alkyl, alkenyl, alkynyl, ot a group of formula: in which Z2, B, R5, P and q are as defined in the description, optionally, the racemic forms thereof, isomers thereof, N-oxydes thereof, and the pharmaceutically acceptable salts thereof, and medicinal products containing the same are useful as specific inhibitors of type-13 matrix metalloprotease.

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.

Compositions useful for treating inflammatory diseases including arthritis are disclosed which comprise cetyl myristoleate compounds or related compounds and at least one compound useful for treatment of inflammatory disease, such as tetracycline compounds, Cox-2 inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, local anaesthetics, chelating agents, matrix metalloprotease inhibitors, inhibitors of inflammatory cytokines, glucosamine, chondroitin sulfate and collagen hydrolysate. Also disclosed are pharmaceutical compositions and methods of treatment for inflammatory disease and local inflammation and dermal irritation. Also disclosed are compositions including tetracycline and at least one compound useful for treatment of inflammatory disease.

Compounds represented by general formula (1) or salts thereof which have a matrix metalloprotease inhibitory activity and are useful as drugs, wherein the rings A and B represent each an optionally substituted homocycle or heterocycle, etc.; R1s are the same or different and each represents hydrogen, optionally substituted hydrocarbyl, acyl, etc.; X1 represents a bond, optionally substituted divalent aliphatic hydrocarbyl, etc.; X2 represents a bond, optionally substituted divalent aliphatic hydrocarbyl, -O-, etc.; Ys are the same or different represents hydrogen, optionally substituted hydrocarbyl, oxo, etc.; m is 0 or 1; n is an integer of 1 to 3; q1 is an integer of 1 to 2n+4; and q2 is an integer of 0 to 2n+3, provided that q1+q2 is 2n+4.

A compound selected from those of formula (I): wherein: X1, X2, and X3, represent N or -CR3 in which R3 is as described in the description, G1 represents a group selected from those of formulae (i / a) and (i / b): in which R4, R5, and R6 are as defined in the description, G2 represents a group selected from carbon-carbon triple bond, -CH=C=CH-, C=O, C=S, S(O)n1 in which n1 represents an integer from 0 to 2 inclusive, or a group of formula (i / c): in which Y1 represents O, S, -NH or -Nalkyl, and Y2 represents O, S, -NH or -Nalkyl, n is an integer from 0 to 6 inclusive, and m is an integer from 0 to 7 inclusive, Z1 represents -CR9R10, wherein R9 and R10 are as defined in the description, A represents a ring system, R1 represents a group selected from H, alkyl, alkenyl, alkynyl, optionally substituted and the group of formula (i / d): in which p, Z2, B, q and G3 are as defined in the description and optionally, its optical isomers, N-oxide, and addition salts thereof with a pharmaceutically-acceptable acid or base, and medicinal products containing the same are useful as specific inhibitors of type-13 matrix mettaloprotease.

Plant extracts and dermatological formulations comprising one or more plant extracts that are capable of inhibiting one or more extracellular proteases selected from the group of: matrix metalloprotease-1 (MMP-1), matrix metalloprotease-2 (MMP-2), matrix metalloprotease-3 (MMP-3), matrix metalloprotease-9 (MMP-9) and human leukocyte elastase (HLE). A rapid method for screening plant extracts to identify those having the above activity that are suitable for incorporation into the dermatological formulations of the invention. The use of the plant extracts as dermatological agents suitable for the treatment or prevention of various dermatological conditions, including wrinkling or sagging of the skin, irradiation induced skin and / or hair damage, deepening of skin lines, elastotic changes in the skin, as well as for the routine care of the skin, hair and / or nails.

A compound of formula (I)wherein X is a -CONHOH group and the R groups are defined in the claims. The compounds are inhibitors of matrix metalloproteinases involved in tissue degradation and inhibitors of the release of tumour necrosis factor from cells.

A compound selected from those of formula (I): wherein: X1, X2, and X3, represent N or -CR3 in which R3 is as described in the description, G1 represents a group selected from those of formulae (i / a) and (i / b): in which R4, R5, and R6 are as defined in the description, G2 represents a group selected from carbon-carbon triple bond, -CH=C=CH-, C=O, C=S, S(O)n1 in which n1 represents an integer from 0 to 2 inclusive, or a group of formula (i / c): in which Y1 represents O, S, -NH or -Nalkyl, and Y2 represents O, S, -NH or -Nalkyl, n is an integer from 0 to 6 inclusive, and m is an integer from 0 to 7 inclusive, Z1 represents -CR9R10 wherein R9 and R10 are as defined in the description, A represents a ring system, R1 represents a group selected from H, alkyl, alkenyl, alkynyl, optionally substituted and the group of formula (i / d): in which p, Z2, B, q and G3 are as defined in the description and optionally, its optical isomers, N-oxide, and addition salts thereof with a pharmaceutically-acceptable acid or base, and medicinal products containing the same are useful as specific inhibitors of type-13 matrix mettaloprotease.

The invention is directed to kits and methods that allow one to predict the risk for preterm labor in a pregnant woman. The inventors have discovered that various extracellular matrix components can be detected in cervical secretions. The quantification of certain extracellular matrix proteins found within cervical secretions can be used as a diagnostic for the biomechanical state of the cervix, which indicates whether preterm labor is likely. Some extracellular matrix components that can be found in cervical secretions include decorin, thrombospondins and matrix metalloproteinases.

Compositions useful for treating inflammatory diseases including arthritis are disclosed which comprise cetyl myristoleate compounds or related compounds and at least one compound useful for treatment of inflammatory disease, such as tetracycline compounds, Cox-2 inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, local anaesthetics, chelating agents, matrix metalloprotease inhibitors, inhibitors of inflammatory cytokines, glucosamine, chondroitin sulfate and collagen hydrolysate. Also disclosed are pharmaceutical compositions and methods of treatment for inflammatory disease and local inflammation and dermal irritation. Also disclosed are compositions including tetracycline and at least one compound useful for treatment of inflammatory disease.

Systems, methods, and apparatuses for modulating proteases including matrix metalloproteinase (MMP), elastase, and bacterial protease in a negative pressure therapy system are described. A mesh having a sacrificial substrate is included. The sacrificial substrate includes a plurality of collagen fibers reinforced with a supporting material and intersecting with each other to form a network of collagen fibers having a plurality openings. The openings of the plurality of openings have an average area between about 0.5 mm2 and about 20 mm2 to permit the flow of negative pressure through the mesh. The sacrificial substrate can also include oxidized regenerated cellulose.

The invention provides an epidermal basement membrane structure formation accelerating preparation and a skin external preparation comprising a serine protease inhibitor, and optionally an accelerator of production of extracellular matrix protein components of the epidermal basement membrane. It also provides, as a means for producing artificial skin having an adequately formed basement membrane, an artificial skin-forming medium which comprises a serine protease inhibitor, and optionally an accelerator of production of extracellular matrix protein components of the epidermal basement membrane and a matrix metalloprotease inhibitor, as well as a method for producing the same.

The present invention provides a novel amide derivative having a matrix metalloproteinase inhibitory activity, and useful as a pharmaceutical agent, which is a compound represented by the formula (I) wherein ring A is an optionally substituted, nitrogen-containing heterocycle, ring B is an optionally substituted monocyclic homocycle or an optionally substituted monocyclic heterocycle, Z is N or NR1 (R1 is a hydrogen atom or an optionally substituted hydrocarbon group), is a single bond or a double bond, R2 is a hydrogen atom or an optionally substituted hydrocarbon group, X is an optionally substituted spacer having 1 to 6 atoms, ring C is (1) an optionally substituted homocycle or (2) an optionally substituted heterocycle other than a ring represented by (II) (X′ is S, O, SO, or CH2), and at least one of ring B and ring C has substituent(s), provided that N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5,6-dimethyl-4-oxo-1,4-dihadrothieno[2,3-d]pyrimidine-2-carboxamide is excluded, or a salt thereof.

The present invention discloses certain di- and polyvalent metal zeolite compounds (formula I) for topical delivery of biological and skin and hair care agents. The method of treating skin and hair condition via topical application of said zeolite compounds is also disclosed. The said method provides a treatment for topical condition, which includes alleviation of skin conditions such as skin rash including diaper rash, dry skin, scalp dandruff, broken or chafed skin, sunburn, skin damage from UV, skin irritation, acne including excess facial oil and facial pore size; darkened skin including age spots, dark circles around the eyes, and discoloration of skin from stretch marks; skin aging including wrinkles and fine lines; loss of collagen including thinning skin and loss of skin pliability; body odor, including oral cavity odor, arm-pit odor, and incontinence odor; cellular inflammation including intracellular and extra cellular inflammation; premature hair aging including premature hair loss hair graying; malfunction of tyrosinase group of enzymes, malfunction of matrix metalloprotease group of enzymes; and combinations thereof. The said method also provides topical delivery of certain metals, including trace metals, and certain zirconium aluminum amino acids that provide antiperspirant benefits;

The invention provides a bone-repairing hydrogel stent and a preparation method thereof. The bone-repairing hydrogel stent comprises a polymer gel carrier and mineralized nano bone particles. The polymer gel carrier comprises polymer gel and matrix metalloprotease responding peptide chains. The matrix metalloprotease responding peptide chains are directly crosslinked to the polymer gel. The bone-repairing hydrogel stent is prepared by 3D printing under the irradiation of UV rays. Furthermore, the invention also relates to a preparation method of the bone-repairing hydrogel stent. The providedbone-repairing hydrogel stent has the advantages of high porosity and mechanical strength, and can intelligently response to mesenchymal stem cells or bone cell systems, promote tissue growth, and induce bone healing. Moreover, the preparation technology is simple, and once moulding can be realized.

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.

Methods for treating arthritis comprising 14-3-3 antagonists that are capable of specifically binding to extracellularly localized 14-3-3 eta and / or 14-3-3 gamma protein isoforms are provided. In preferred embodiments, the 14-3-3 antagonist is an inhibitory peptide or an anti-14-3-3 antibody. The 14-3-3 antagonists are also formulated in a pharmaceutical composition and used in a method for reducing matrix metalloprotease (MMP) expression in the synovial fluid of a patient, wherein the MMP is MMP-1 or MMP-3.

A treatment process is disclosed that comprises administering an effective amount of an aromatic sulfone hydroxamic acid that exhibits excellent inhibitory activity of one or more matrix metalloprotease (MMP) enzymes, such as MMP-2, MMP-9, and MMP-13, while exhibiting substantially less inhibition at least of MMP-1 to a host having a condition associated with pathological matrix metalloprotease activity. The administered enzyme inhibitor corresponds in structure to formula (I), below, or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are both hydrido or R1 and R2 together with the atoms to which they are bonded form a 5- to 8-membered ring containing one, two, or three heteroatoms in the ring that are oxygen, sulfur, or nitrogen. R3 in formula (I) is an optionally substituted aryl or optionally substituted heteroaryl radical. Also disclosed are metalloprotease inhibitor compounds having those selective activities, processes for manufacture of such compounds and pharmaceutical compositions using an inhibitor.

The present invention relates to an inhibitor of matrix metalloprotease (MMP) production and tumor necrosis factor (TNF) production, and medicines for the treatment of diseases such as chronic rheumatoid arthritis, osteoarthritis, allergic diseases, psoriasis, transplant rejection, arterial sclerosis, ischemic re-perfusion disorder, diabetic nephritic and ocular diseases, cancer, autoimmune glomerulonephritis, infectious diseases, Crohn's disease, inflammatory intestinal diseases and autoimmune hepatitis, each comprising certain polyazanaphthalene compounds or pharmaceutically acceptable salts thereof as active ingredients.

This invention provides novel heterocyclic derived matrix metalloprotease inhibitors of the formula: and pharmaceutical compositions comprising same, useful for treating disorders ameliorated by antagonizing matrix metalloproteases. This invention also provides therapeutic and prophylactic methods using the instant pharmaceutical compositions.

The present invention relates to compositions comprising extracts of Durio zibethinus. The compositions of the present invention are useful for improving the appearance, texture, and / or moisture of mammalian skin. In particular, the compositions of the present invention decrease inflammation in the skin, inhibit matrix metalloprotease-9, which degrades skin proteins such as collagen and elastin, and inhibit melanogenesis in the skin.

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.

Matrix metalloproteases (MMPs) play many important roles in normal and pathological remodeling processes including atherothrombotic disease, inflammation, angiogenesis and cancer. This invention relates to the activation of protease-activated receptor-1 (PAR-1) by endogenous platelet MMP-1 collagenase on the surface of platelets. Exposure of platelets to fibrillar collagen converts the surface-bound pro-MMP-1 zymogen to active MMP-1, which promotes aggregation through PAR-1, MMP-1 is shown to cleave the PAR-1 extracellular domain at a novel site, which then strongly activates Rho-GTP signaling pathways, cell shape change and motility, and MAPK signaling. Blockade of MMP-PAR 1 suppresses thrombogenesis under arterial flow conditions and inhibited thrombosis in animals. These studies provide a link between matrix-dependent activation of metalloproteases and platelet-G protein signaling and identify MMP-1 / PAR-1 as a new target for the treatment and prevention of arterial thrombosis and other thrombotic diseases.

A compound represented by the formula: wherein X represents a sulfur atom or an oxygen atom; Y represents an optionally oxidized sulfur atom or an oxygen atom; Z represents a bond or a divalent hydrocarbon group; R1 represents an optionally substituted hydrocarbon group; R2 represents an optionally amidated or esterified carboxyl group; ring A represents an optionally substituted aromatic 5-membered heterocyclic ring; or a salt thereof. A compound of the above formula possesses cell differentiation inducing factor action-enhancing activity and anti-matrix metalloprotease activity and that is useful in the prevention and treatment of bone diseases such as osteoporosis, bone fractures, osteoarthritis and rheumatoid arthritis, arteriosclerosis, cancer metastasis, and diseases based on nerve degeneration.

The invention provides an epidermal basement membrane structure formation accelerating preparation and a skin external preparation comprising a serine protease inhibitor, and optionally an accelerator of production of extracellular matrix protein components of the epidermal basement membrane. It also provides, as a means for producing artificial skin having an adequately formed basement membrane, an artificial skin-forming medium which comprises a serine protease inhibitor, and optionally an accelerator of production of extracellular matrix protein components of the epidermal basement membrane and a matrix metalloprotease inhibitor, as well as a method for producing the same.

The present invention provides compositions and methods for inhibiting abnormal cell growth. In particular, the invention provides nucleic acids encoding Diphtheria toxin fusion proteins comprising residues 1-388 of Diphtheria toxin, wherein the native furin cleavage site has been substituted for a matrix metalloproteinase or plasminogen activator cleavage site, and a heterologous polypeptide and the polypeptides encoded by such nucleic acids. In addition, the invention provides methods of treating cancer by administering such polypeptides.