214 results about "Matrix metalloproteinase inhibitor" patented technology

The application of matrix metalloproteinase (MMP) inhibitors to the skin inhibits the degradation of proteins found in the skin including collagen, elastin, and other basement membrane and extracellular matrix protein. MMP inhibitors may be used in both cosmetic compositions and pharmaceutical compositions for application to skin. MMP inhibitors are formulated with a cosmetically suitable vehicle or pharmaceutically acceptable excipient for application to the skin as creams, lotions, ointments, solutions, face masks, etc. As cosmetics, the inventive MMP inhibitor compositions are applied to the skin to prevent or reduce the appearance of wrinkles, pigmentation changes, loss of elasticity, or other effects associated with aging or sun damage. As pharmaceuticals, the inventive MMP inhibitor compositions may also be applied to the skin to treat or prevent a skin disease (e.g., proliferative disease, inflammatory disease).

A system and compositions including zotarolimus and paclitaxel are disclosed, as well as methods of delivery, wherein the drugs have effects that complement each other. Medical devices are disclosed which include supporting structures that include at least one pharmaceutically acceptable carrier or excipient, which carrier or excipient can include one or more therapeutic agents or substances, with the carrier including at least one coating on the surface thereof, and the coating associated with the therapeutic substances, such as, for example, drugs. Supporting structures for the medical devices that are suitable for use in this invention include, but are not limited to, coronary stents, peripheral stents, catheters, arterio-venous grafts, by-pass grafts, and drug delivery balloons used in the vasculature. These compositions and systems can be used in combination with other drugs, including anti-proliferative agents, anti-platelet agents, anti-inflammatory agents, anti-thrombotic agents, cytotoxic drugs, agents that inhibit cytokine or chemokine binding, cell de-differentiation inhibitors, anti-lipaedemic agents, matrix metalloproteinase inhibitors, cytostatic drugs, or combinations of these and other drugs.

A method of using an MMP inhibitor and optionally radiation therapy, and one or more antineoplastic agents of the topoisomerase class selected from the group consisting of irinotecan and topotecan, as a combination therapy for the treatment of neoplasia is disclosed.

Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-alpha converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-alpha from membrane bound TNF-alpha precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF-alpha converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection having the formulawherein R2 and R3 form a heterocyclic ring and A is S, S(O), or S(O)2, and R1 and R4 are defined herein.

Systems and compositions comprising zotarolimus that are safer, more effective and produce less inflammation than rapamycin and paclitaxel systems are disclosed. Medical devices comprising supporting structures capable of containing or supporting a pharmaceutically acceptable carrier or excipient, which carrier or excipient can contain one or more therapeutic agents or substances, with the carrier including a coating on the surface thereof, and the coating having the therapeutic compounds, including, for example, drugs. Supporting structures for the medical devices that are suitable for use in this invention include coronary stents, peripheral stents, catheters, arterio-venous grafts, by-pass grafts, and drug delivery balloons used in the vasculature. These compositions and systems can be used in combination with other drugs, including anti-proliferative agents, anti-platelet agents, anti-inflammatory agents, anti-thrombotic agents, cytotoxic drugs, agents that inhibit cytokine or chemokine binding, cell de-differentiation inhibitors, anti-lipaedemic agents, matrix metalloproteinase inhibitors, cytostatic drugs, or combinations of these and other drugs.

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.

The present invention provides methods to treat or prevent neoplasia disorders in a mammal using a combination of a matrix metalloproteinase inhibitor and an antineoplastic agent.

A system and compositions including zotarolimus and paclitaxel are disclosed, as well as methods of delivery, wherein the drugs have effects that complement each other. Medical devices are disclosed which include supporting structures that include at least one pharmaceutically acceptable carrier or excipient, which carrier or excipient can include one or more therapeutic agents or substances, with the carrier including at least one coating on the surface thereof, and the coating associated with the therapeutic substances, such as, for example, drugs. Supporting structures for the medical devices that are suitable for use in this invention include, but are not limited to, coronary stents, peripheral stents, catheters, arterio-venous grafts, by-pass grafts, and drug delivery balloons used in the vasculature. These compositions and systems can be used in combination with other drugs, including anti-proliferative agents, anti-platelet agents, anti-inflammatory agents, anti-thrombotic agents, cytotoxic drugs, agents that inhibit cytokine or chemokine binding, cell de-differentiation inhibitors, anti-lipaedemic agents, matrix metalloproteinase inhibitors, cytostatic drugs, or combinations of these and other drugs.

A medical device comprising a supporting structure capable of including or supporting a pharmaceutically acceptable carrier or excipient, which carrier or excipient may include one or more therapeutic agents or substances, with the carrier including a coating on the surface thereof, and the coating including the therapeutic substances, such as, for example, drugs. Supporting structures for the medical devices that are suitable for use in this invention include, but are not limited to, coronary stents, peripheral stents, catheters, arterio-venous grafts, by-pass grafts, and drug delivery balloons used in the vasculature. Drugs that are suitable for use in this invention include, but are not limited to, This drug can be used in combination with another drug including those selected from anti-proliferative agents, anti-platelet agents, anti-inflammatory agents, anti-thrombotic agents, cytotoxic drugs, agents that inhibit cytokine or chemokine binding, cell de-differentiation inhibitors, anti-lipaedemic agents, matrix metalloproteinase inhibitors, cytostatic drugs, or combinations of these drugs.

A compound selected from those of formula (I): in which: W represents N or C-R1; in which R1 is as defined in the description, X represents N or C-R2 in which R2 is as defined in the description, Y represents a group selected from oxygen, sulfur, -NH, and -Nalkyl, Z represents a group selected from oxygen, sulphur, -NR8 in which R8 is as defined in the description, and optionally carbon depending the definition of Y, n is an integer from 0 to 8 inclusive, Z1 represents a group -CR9R10 wherein R9 and R10, are as defined in the description, which group contains optionally multiple bonds or heteroatomes, A represents a cyclic group, m is an integer from 0 to 7 inclusive, the group(s) R4 is (are) as defined in the description, R3 represents a group selected from hydrogen, alkyl, alkenyl, alkynyl, and the group of formula: in which p, Z2, B, q, and R13 are as defined in the description, optionally, its racemic forms, isomers thereof, N-oxydes thereof, and its the pharmaceutically acceptable salts thereof, and medicinal products containing the same are useful as specific inhibitors of type-13 matrix mettaloprotease.

A medical device comprising a supporting structure capable of containing or supporting a pharmaceutically acceptable carrier or excipient, which carrier or excipient may contain one or more therapeutic agents or substances, with the carrier preferably including a coating on the surface thereof, and the coating containing the therapeutic substances, such as, for example, drugs. Supporting structures for the medical devices that are suitable for use in this invention include, but are not limited to, coronary stents, peripheral stents, catheters, arterio-venous grafts, by-pass grafts, and drug delivery balloons used in the vasculature. Drugs that are suitable for use in this invention include, but are not limited to, This drug can be used in combination with another drug including those selected from anti-proliferative agents, anti-platelet agents, anti-inflammatory agents, anti-thrombotic agents, cytotoxic drugs, agents that inhibit cytokine or chemokine binding, cell de-differentiation inhibitors, anti-lipaedemic agents, matrix metalloproteinase inhibitors, cytostatic drugs, or combinations of these drugs.

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; R 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) novel 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.

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.

Medical devices comprising an interventional component for delivering multiple beneficial agents in which a hydration inhibitor controls release of at least one beneficial agent from the device. The hydration inhibitor is relatively less hydrophilic than the beneficial agent and preferably is a drug. Suitable beneficial agents include (I) dexamethasone, estradiol, anti-proliferative agents, anti-platelet agents, anti-inflammatory agents, anti-thrombotic agents, cytotoxic drugs, agents that inhibit cytokine or chemokine binding, cell de-differentiation inhibitors, anti-lipacdemic agents, matrix metalloproteinase inhibitors, cytostatic drugs, or combinations of these drugs, radiopaque markers, beta-carotene, tocopherols, tocotrienols, and antioxidants

Compositions and methods are provided for ameliorating various effects of UVA and UVB radiation, especially from the sun. The compositions include an ingredient that prevents photoaging from MED and subMED radiation, namely an MMP (matrix metalloproteinase) inhibitor, especially formulated for oral administration, and more especially formulated for controlled-release so as to provide the MMP inhibitor when MMP induction (including upstream signalling molecules like c-JUN, and / or MMPs like stromelysin) is most prevalent.

This invention provides compounds defined by Formula I or a pharmaceutically acceptable salt thereof,wherein R1, Q, Y2, Y3, Y4, U5, U6, U8, and R2 are as defined in the specification. The invention also provides pharmaceutical compositions comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, as defined in the specification, together with a pharmaceutically acceptable carrier, diluent, or excipient. The invention also provides methods of inhibiting an MMP-13 enzyme in an animal, comprising administering to the animal a compound of Formula I, or a pharmaceutically acceptable salt thereof. The invention also provides methods of treating a disease mediated by an MMP-13 enzyme in a patient, comprising administering to the patient a compound of Formula I, or a pharmaceutically acceptable salt thereof, either alone or in a pharmaceutical composition. The invention also provides methods of treating diseases such as heart disease, multiple sclerosis, osteo- and rheumatoid arthritis, arthritis other than osteo- or rheumatoid arthritis, cardiac insufficiency, inflammatory bowel disease, heart failure, age-related macular degeneration, chronic obstructive pulmonary disease, asthma, periodontal diseases, psoriasis, atherosclerosis, and osteoporosis in a patient, comprising administering to the patient a compound of Formula I, or a pharmaceutically acceptable salt thereof, either alone or in a pharmaceutical composition. The invention also provides combinations, comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, together with another pharmaceutically active component as described in the specification.

A system and compositions including zotarolimus and paclitaxel are disclosed, as well as methods of delivery, wherein the drugs have effects that complement each other. Medical devices are disclosed which include supporting structures that include at least one pharmaceutically acceptable carrier or excipient, which carrier or excipient can include one or more therapeutic agents or substances, with the carrier including at least one coating on the surface thereof, and the coating associated with the therapeutic substances, such as, for example, drugs. Supporting structures for the medical devices that are suitable for use in this invention include, but are not limited to, coronary stents, peripheral stents, catheters, arterio-venous grafts, by-pass grafts, and drug delivery balloons used in the vasculature. These compositions and systems can be used in combination with other drugs, including anti-proliferative agents, anti-platelet agents, anti-inflammatory agents, anti-thrombotic agents, cytotoxic drugs, agents that inhibit cytokine or chemokine binding, cell de-differentiation inhibitors, anti-lipaedemic agents, matrix metalloproteinase inhibitors, cytostatic drugs, or combinations of these and other drugs.

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.

A medical device comprising a supporting structure capable of containing or supporting a pharmaceutically acceptable carrier or excipient, which carrier or excipient may contain one or more therapeutic agents or substances, with the carrier preferably including a coating on the surface thereof, and the coating containing the therapeutic substances, such as, for example, drugs. Supporting structures for the medical devices that are suitable for use in this invention include, but are not limited to, coronary stents, peripheral stents, catheters, arterio-venous grafts, by-pass grafts, and drug delivery balloons used in the vasculature. Drugs that are suitable for use in this invention include, but are not limited to,This drug can be used in combination with another drug including those selected from anti-proliferative agents, anti-platelet agents, anti-inflammatory agents, anti-thrombotic agents, cytotoxic drugs, agents that inhibit cytokine or chemokine binding, cell de-differentiation inhibitors, anti-lipaedemic agents, matrix metalloproteinase inhibitors, cytostatic drugs, or combinations of these drugs.

The present invention relates to a composition comprising Melissa leaf extract that inhibits angiogenesis and matrix metalloproteinase activity. The Melissa leaf extract of the present invention inhibits angiogenesis and activity of matrix metalloproteinase, so that it can be applied to treat or prevent diseases related to angiogenesis and matrix metalloproteinase. The composition of the present invention comprising Melissa leaf extract may also comprise more than one component of the other anti-angiogenic, anti-cancer, anti-inflammatory and anti-aging components. This particular composition comprising Melissa leaf extract can be used for pharmaceutical, dietetic and / or cosmetic purposes.

The invention provides isolated MMP-2, MMP-9 and MT1-MMP selective substrate polypeptides or functional peptidomimetics. The selective substrate polypeptides contain the following sequences: MMP-2 selective substrate polypeptides contain SEQ ID NOS:1-27, MMP-9 selective substrate polypeptides contain SEQ ID NOS:28-35, and MT1-MMP selective substrate polypeptide contain SEQ ID NOS:36-40. In addition, the invention provides a method of preferentially directing a moiety to a site of MMP-2 activity by administering to a subject an effective amount of an isolated MMP-2 selective substrate polypeptide containing SEQ ID NOS:45-47 linked to a moiety. Also provided is a method of preferentially directing a moiety to a site of MMP-9 activity by administering to a subject an effective amount of an isolated MMP-9 selective substrate polypeptide containing SEQ ID NO:44 linked to a moiety, and preferentially directing a moiety to a site of MT1-MMP activity by administering to a subject an effective amount of an isolated MT1-MMP selective substrate polypeptide containing SEQ ID NOS:36-40 linked to a moiety.

Compounds of formula (I) wherein n, V, R1, R2, R3 and R4 are as defined in the specification are matrix metalloproteinase inhibitors.

Peptoid compounds of Formula I and Formula II are disclosedThe compounds are useful in the treatment of matrix metalloproteinase-mediated disorders.

This invention provides compounds defined by Formula Iand pharmaceutically acceptable salts thereof,and pharmaceutical compositions comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier, diluent, or excipient. The invention also provides methods of treating osteo- and rheumatoid arthritis.

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.

Systems and compositions comprising paclitaxel and a second drug, such as rapamycin, analogs, derivatives, salts and esters thereof are disclosed, as well as methods of delivery wherein the drugs have effects that complement each other. Medical devices comprising supporting structures capable of including or supporting a pharmaceutically acceptable carrier or excipient, which carrier or excipient can contain one or more therapeutic agents or substances, with the carrier preferably including a coating on the surface thereof, and the coating including the therapeutic substances, such as, for example, drugs. Supporting structures for the medical devices that are suitable for use in this invention include coronary stents, peripheral stents, catheters, arterio-venous grafts, by-pass grafts, and drug delivery balloons used in the vasculature. These compositions and systems can be used in combination with other drugs, including anti-proliferative agents, anti-platelet agents, anti-inflammatory agents, anti-thrombotic agents, cytotoxic drugs, agents that inhibit cytokine or chemokine binding, cell de-differentiation inhibitors, anti-lipaedemic agents, matrix metalloproteinase inhibitors, cytostatic drugs, or combinations of these and other drugs.

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.

This invention provides compounds defined by Formula I or a pharmaceutically acceptable salt thereof,wherein R1, Q, Y1, Y2, Y3, and R2 are as defined in the specification. The invention also provides pharmaceutical compositions comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, as defined in the specification, together with a pharmaceutically acceptable carrier, diluent, or excipient. The invention also provides methods of inhibiting an MMP-13 enzyme in an animal, comprising administering to the animal a compound of Formula I, or a pharmaceutically acceptable salt thereof. The invention also provides methods of treating a disease mediated by an MMP-13 enzyme in a patient, comprising administering to the patient a compound of Formula I, or a pharmaceutically acceptable salt thereof, either alone or in a pharmaceutical composition. The invention also provides methods of treating diseases such as heart disease, multiple sclerosis, osteo- and rheumatoid arthritis, arthritis other than osteo- or rheumatoid arthritis, cardiac insufficiency, inflammatory bowel disease, heart failure, age-related macular degeneration, chronic obstructive pulmonary disease, asthma, periodontal diseases, psoriasis, atherosclerosis, and osteoporosis in a patient, comprising administering to the patient a compound of Formula I, or a pharmaceutically acceptable salt thereof, either alone or in a pharmaceutical composition. The invention also provides combinations, comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, together with another pharmaceutically active component as described in the specification.