99 results about "Bradykinin" patented technology

A complex is provided for the treatment of neurogenic conditions having the formula:

where R¹ is

M is a metal ion Ca(II), Mg(II), Cu(II) or Ni(II); n is an integer 1 or 2; R is BBB peptide, transferrin, membrane transporter peptide, TAT peptide, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptidegluconate, L-lactate, L-leucine, L-tryptophan, and L-glutamate; and R is coupled to M through a carboxylate moiety. Magnesium (II) represents the preferred metal ion as magnesium is known to have neuroprotective effects. The metal ion is in part chelated by a non-steroidal anti-inflammatory drug that does not inhibit platelet activity and includes salicylate and ibuprofenate. The complex also includes a ligand operative in transport across the blood brain barrier. A process for making an inventive complex includes the stoichiometric addition of ligands containing carboxylate groups to a solution of the metal ion. In instances where the metal ion is magnesium (II), a stoichiometric ratio of 1:1:1 is found between the non-steroidal anti-inflammatory ligand:magnesium (II):transporter ligand.

Novel backbone cyclized peptide analogs are formed by means of bridging groups attached via the alpha nitrogens of amino acid derivatives to provide novel non-peptidic linkages. Novel building units disclosed are N^α(ω-functionalized) amino acids constructed to include a spacer and a terminal functional group. One or more of these N^α(ω-functionalized) amino acids are incorporated into a peptide sequence, preferably during solid phase peptide synthesis. The reactive terminal functional groups are protected by specific protecting groups that can be selectively removed to effect either backbone-to-backbone or backbone-to-side chain cyclizations. The invention is specifically exemplified by backbone cyclized bradykinin antagonists having biological activity. Further embodiments of the invention are somatostatin analogs having one or two ring structures involving backbone cyclization.

A compound is provided that has the formula

NH₂CH₂CH₂CH₂C(O)N—R   (I)

where R is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine blood brain barrier (BBB) peptide, membrane translocating protein, TAT peptides, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptidetransferrin, glucosylamnine, amino saccharin, lactylamine, leucine, tryptophan, glutamate and amino cholines.

Substituted spiroamide compounds corresponding to formula (I):

wherein A, B, Q¹, Q², Q³, Q⁴, R¹, R⁸, R^9a, R^9b, R¹², R¹³, R²⁰⁰ and R²¹⁰ have defined meanings, processes for their preparation, pharmaceutical compositions containing such compounds, and the use of such compounds for treating or inhibiting pain or other conditions mediated at least in part by the bradykinin 1 receptor (B1R).

The present invention relates to novel antagonists to a B₁-bradykinin (B₁-BK) receptor which have a good affinity and selectivity therefor, some of which being at least partially resistant to enzymatic degradation. The synthesis of the B₁ receptors is induced during inflammation. Symptoms associated with inflammation (elevated hydrostatic pressure and plasma leakage or extravasation) have been observed in diabetic animal models (streptozotocin-induced diabetes (STZ)) as well as in spontaneously hypertensive rats (SHR). The present inventors confirm the presence of B₁-BK receptors in these two models. B₁-BK antagonists abolished the vasocontraction induced by B₁-BK in SHR and STZ, and reduced the glycemia of diabetic animals to normal levels. The present B₁-antagonists are useful for treating any condition wherein B₁-receptor is expressed, particularly during inflammation, and more particularly wherein B₁-receptor expression results in diabetic vasculopathy, other diabetic symptoms associated with an insulitis and a post-capillary resistance building as a consequence of the presence of a B₁-receptor.

A compound is provided that has the formula

NH₂CH₂CH₂CHR¹C(O)N—R  (I)

where R¹ is p-chlorophenyl, R is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine blood brain barrier (BBB) peptide, membrane translocating protein, TAT peptides, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptide transferrin, glucosylamine, amino saccharin, lactylamine, leucine, tryptophan, glutamate and amino cholines.

A method of diagnosing Alzheimer's disease in a patient comprises determining whether the phosphorylation level of an indicator protein in cells of the patient after stimulus with an activator compound is abnormally elevated as compared to a basal phosphorylation level, the indicator protein being e.g. Erk1/2 and the activator compound being e.g. bradykinin.

A method and apparatus for preventing and treating septicemia in patient blood is provided. The extracorporeal system includes an antimicrobial device to inactivate at least 99% of bloodborne microorganisms, a hemoconcentrator/filtration unit to remove approximately 50-75% of target molecules from the patient blood and a filter unit to remove target molecules from patient blood from the sieved plasma filtrate. Target molecules are produced by microorganisms, as well as by the patient's cells. These molecules include endotoxins from Gram negative bacteria, exotoxins from Gram negative and Gram positive bacteria, as well as RAP protein mediator from Staphylococcus aureus, and cell mediators such as tumor necrosis factor-alpha, and interleukin 1-beta, interleukin 6, complement proteins C3a and C5a, and bradykinin.

Disclosed herein are methods for the treatment or prevention of rosacea in a patient, including administering a compound that inhibits one or more components of the bradykinin activation pathway in an amount sufficient to reduce or prevent one or more symptoms of rosacea.

A method and apparatus for preventing and treating septicemia in patient blood is provided. The extracorporeal system includes an antimicrobial device to inactivate at least 99% of bloodborne microorganisms, a hemoconcentrator/filtration unit to remove approximately 50-75% of target molecules from the patient blood and a filter unit to remove target molecules from patient blood from the sieved plasma filtrate. Target molecules are produced by microorganisms, as well as by the patient's cells. These molecules include endotoxins from Gram negative bacteria, exotoxins from Gram negative and Gram positive bacteria, as well as RAP protein mediator from Staphylococcus aureus, and cell mediators such as tumor necrosis factor-alpha, and interleukin 1-beta, interleukin 6, complement proteins C3a and C5a, and bradykinin.

The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion to apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell wherein the Targeting Moiety is selected from the group consisting of BAM, β-endorphin, bradykinin, substance P, dynorphin and/or nociceptin.

The present invention provides compounds of formula (I)

as well as the use of such compounds in pharmaceutical compositions and methods of treatment.

The compounds described herein represent a class of TAFIa inhibitors suitable for use in treating conditions such as thrombosis, atherosclerosis, adhesions, dermal scarring, cancer, fibrotic conditions, inflammatory diseases and those conditions which benefit from maintaining or enhancing bradykinin levels in the body.

Disclosed are methods of selectively delivering a medicant to an abnormal brain region and/or to a malignant tumor In a mammalian subject, including a human. A medicant is administered simultaneously or substantially simultaneously with a potassium channel agonist (other than bradykinin or a bradykinin analog), such as NS-1619,1-EBIO, a guanylyl cyclase activator, a guanylyl cyclase activating protein, minoxidil, pinacidil, cromakalim, or levcromakalim, whereby the medicant is delivered selectively to the cells of the abnormal brain region and/or to the tumor, compared to normal tissues. Thus, among the disclosures is a method of treating a malignant tumor in a human subject. Also disclosed are pharmaceutical compositions that combine a potassium channel agonist together with a medicant and a kit for enhancing the delivery of a medicant to an abnormal brain region and/or to a malignant tumor.