129results about "Gastrins/cholecystokinins" patented technology

Compounds of the formulas LAn-Z-X-WwD and BZ-X-WwD wherein: D is a drug moiety; L is a ligand; B is a blocking group; A is an optional acyl unit; Z is an amino acid or a peptide; X is an aminobenzyl ether self-immolative spacer group; W is an optional second self-immolative group; n is an integer of 0 or 1; and w is an integer of 0 or 1, and compositions of said compounds with pharmaceutically acceptable carrier, diluent and / or excipient, and methods of delivery the drug D via the compounds.

The present invention relates generally to novel, selectable hybrid polypeptides useful as agents for the treatment and prevention of metabolic diseases and disorders which can be alleviated by control plasma glucose levels, insulin levels, and / or insulin secretion, such as diabetes and diabetes-related conditions. Such conditions and disorders include, but are not limited to, hypertension, dyslipidemia, cardiovascular disease, eating disorders, insulin-resistance, obesity, and diabetes mellitus of any kind, including type 1, type 2, and gestational diabetes.

The invention relates to a nutritional intervention composition in powder form that is taken before a meal and that extends post meal satiety. The compositions of the invention are comprised of at least one protein, C12-18 fatty acids, preferably oleic acid, all of which stimulate CCK release in the body, and a source of proteinase inhibitor which acts to prevent the deactivation of CCK. The subject compositions preferably additionally contain a source of calcium and are advantageous in that they utilize a source of proteinase inhibitor as opposed to the more costly extracts. The source of proteinase inhibitor is advantageously an extract of potato, soy, or beans containing about 10 weight percent of proteinase inhibitor. The powder compositions are mixed with a suitable liquid, preferably water, prior to ingestion.

The present invention relates to an expression vector for animal cells. Specifically, the present invention relates to an expression vector, pMS vector, pSG vector and pMSG vector, including the human β-globin 5′ MAR complementary sequence or / and the transcription termination site of the gastrin gene. An expression system using an expression vector of the present invention can successfully produce recombinant proteins in various animals cells and recombinant protein having a unique structure and function.

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.

This invention relates to compositions for the sustained release of biologically active polypeptides, and methods of forming and using said compositions, for the sustained release of biologically active polypeptides. The sustained release compositions of this invention comprise a biocompatible polymer having dispersed therein, a biologically active polypeptide and a sugar.

Disclosed are a method and a corresponding pharmaceutical composition for treating damaged cartilage and subchondral bone. Neurogenic compounds in general and neuropeptides in particular have been found to be highly effective in stimulated repair of cartilage and bone damaged due to traumatic injury, ligament disease, and disuse. Preferred active ingredients for use in the method and corresponding pharmaceutical composition include calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), dynorphin, enkephalin, galanin, neuropeptide Y (NPY), neurotensin, somatostatin, substance P (SP), thyrotropin-releasing hormone (TRH), vasoactive intestinal peptide (VIP).

The invention concerns immunogens, immunogenic compositions and method for the treatment of gastrin-dependent tumors. The immunogens comprise a peptide from the CCK-B / gastrin-receptor conjugated to a spacer and to an immunogenic carrier. The immunogens are capable of inducing antibodies in vivo which bind to the CCK-B / gastrin-receptor in tumor cells, thereby preventing growth stimulating peptide hormones from binding to the receptors, and inhibiting tumor cell growth. The immunogens also comprise antibodies against the CCK-B / gastrin-receptor for passive immunization. The invention also concerns diagnostic methods for detecting gastrin-dependent tumors in vivo or from a tissue biopsy using the antibodies of the invention.

This invention relates to compositions for the sustained release of biologically active polypeptides, and methods of forming and using said compositions, for the sustained release of biologically active polypeptides. The sustained release compositions of this invention comprise a biocompatible polymer having dispersed therein, a biologically active polypeptide and a sugar.

Compositions and methods for islet neogenesis therapy comprising an EGF and a gastrin in combination with immune suppression, and for treating or preventing early stage diabetes with a gastrin / CCK receptor ligand and an immunosuppressant are provided.

The invention provides for a formulation for coating one or more microprojections using a non-volatile counterion to improve solubility of a biologically active agent. The invention also includes formulations having a volatile counterion to reduce the solubility of a portion of the biologically active agent.

A conjugate comprising a ligand, a linker, and a cytotoxic agent, in which the linker is FALA, VLALA, ALAL, ALALA, ChaLALA, ChaChaLAL, NalChaLAL or NalLALA; a composition thereof; a method of delivering a cytotoxic agent in a cell-specific manner; and a method of treating cancer in a mammal.

The present invention relates to the compositions, methods, and applications of a new approach to pattern recognition based targeting by which an exponential amplification of effector response can be specifically obtained at a targeted cells. The purpose of this invention is to enable the selective delivery of large quantities of an array of effector molecules to target cells for diagnostic or therapeutic purposes. The invention is comprised of two components designated as “Compound 1” and “Compound 2”: Compound 1 is comprised of a cell binding agent and a masked female adaptor. Compound 2 is comprised of a male ligand, an effector agent, and two or more masked female receptors. The male ligand is selected to bind with high affinity to the female adaptor. Compound 1 can bind with high affinity to the target cell and the female receptor can then be unmasked by an enzyme enriched at the tumor cell. The male ligand of Compound 2 can then bind to the unmasked female adaptor bound to the target cell. The masked female adaptor on the bound Compound 2 can then be specifically unmasked. One receptor has in effect become two. Two new molecules of Compound 2 can bind to the unmasked adaptors receptors. After unmasking two receptors in effect become four. The process can continue in an explosive exponential like fashion resulting in enormous amplification of the number of effector molecules specifically deposited at the target cell.

This invention relates to compositions for the sustained release of biologically active polypeptides, and methods of forming and using said compositions, for the sustained release of biologically active polypeptides. The sustained release compositions of this invention comprise a biocompatible polymer having dispersed therein, a biologically active polypeptide and a sugar.

Compounds according to the formula: 1 and pharmaceutically acceptable salts, solvates or hydrates thereof, wherein group Ar is optionally substituted (C.sub.6-C.sub.10)aryl or (C.sub.1-C.sub.9)heteroaryl; X is a direct link, --CH.sub.2 --, --SO.sub.2 --, --CO--, --CHR.sup.1-- where R.sup.1 is(C.sub.1-C.sub.6) alkyl, or --CR.sup.1'R.sup.1"-where both R.sup.1' and R.sup.1" are, independently, (C.sub.1-C.sub.6)alkyl; Y is N or CH; and Z and W are as herein defined, and pharmaceutical compositions thereof, and methods useful to facilitate secretion of growth hormone(GH) in mammals.

The present invention relates to amphiphilic drug-oligomer conjugates capable of traversing the blood-brain barrier ("BBB") and to methods of making and using such conjugates. An amphiphilic drug-oligomer conjugate comprises a therapeutic compound conjugated to an oligomer, wherein the oligomer comprises a lipophilic moiety coupled to a hydrophilic moiety. The conjugates of the invention further comprise therapeutic agents such as proteins, peptides, nucleosides, nucleotides, antiviral agents, antineoplastic agents, antibiotics, etc., and prodrugs, precursors, derivatives and intermediates thereof, chemically coupled to amphiphilic oligomers.

New and improved compounds for use in radiodiagnostic imaging or radiotherapy having the formula M-N-O-P-G, wherein M is the metal chelator (in the form complexed with a metal radionuclide or not), N-O-P is the linker, and G is the GRP receptor targeting peptide. Methods for imaging a patient and / or providing radiotherapy to a patient using the compounds of the invention are also provided. A method for preparing a diagnostic imaging agent from the compound is further provided. A method for preparing a radiotherapeutic agent is further provided.

A nutritional supplement composition having therapeutically effective amounts of milk minerals including calcium, a protein source including κ-casein fragment 106-169, and enzyme-inhibiting peptides is provided for the treatment of body weight conditions. The nutritional supplement composition is administered in amounts effective for limiting weight gain and / or enhancing weight loss, as well as promoting overall good health, in the treatment of body weight conditions, including overweight and obesity.

Compositions and methods are provided for islet neogenesis therapy comprising a member of a group of factors that complement a gastrin / CCK receptor ligand, with formulations, devices and methods for sustained release delivery and for local delivery to target organs.

An embodiment of the invention provided herein is a pharmaceutical composition comprising a gastrin compound having an extended activity upon administration to a subject in comparison with native gastrin. Methods are provided of conjugating portions of the amino acid sequence of gastrin having functional ability to bind to the gastrin / CCK receptor, to various carrier moieties, including the use of amino acid spacer regions, and use of bifunctional cross-linking reagents. Methods of treating a diabetes patient with the compositions are provided.

The invention provides for methods and compositions for treatment of pain via craniofacial mucosal administration of an analgesic compound (e.g. a non-opioid analgesic peptide, an NOP agonist or N / OFQ). Intranasal administration of certain analgesic peptides such as N / OFQ results in global analgesic effects.

The Present invention relates generally to novel GIP analogs and GIP hybrid polypeptides with selectable properties, useful as agents for the treatment and prevention of metabolic diseases and disorders, for example those which can be alleviated by control plasma glucose levels, insulin levels, and / or insulin secretion, positive inotropic effects, reduction of catabolic effects, slowing of gastric emptying. Such conditions and disorders include, but are not limited to, hypertension, dyslipidemia, cardiovascular disease, eating disorders, critical care, insulin-resistance, obesity, and diabetes mellitus of any kind, including type 1, type 2, and gestational diabetes.

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.

Serum-associated hypergastrinemia is treated by administration of gastrin active or passive immunization. An anti-gastrin immunogenic composition containing a gastrin G17 or G34 peptide fragment which is amino acid spacer-linked to an immunogenic carrier, is administered so as to effectively neutralize the circulating gastrin hormone, and moreover, inhibit autocrine activity by progastrin such as Gly-extended G17, and amidated G17, in patients with pernicious anemia. Moreover, the method includes administration of a therapeutically effective amount of anti-G17 or anti-G34 antibodies which may be in humanized form. Finally, the method provides ameliorating treatment of hypergastrinemic effects of proton pump inhibitors or H2 histamine receptor blocking agents or antagonists, in addition to treatment of hypergastrinemia caused by diseases such as pernicious anemia.

Immmunogenic compositions useful for the treatment of ulcers or tumors whose growth is dependent on or stimulated by gastrin hormones are disclosed. The immunogenic compositions induce antibodies in a subject which selectively neutralize the specific hormones. Pharmaceutical compositions comprising effective amounts of the immunogenic compositions and methods of treatment using the compositions are disclosed. A method of reversing the inventive treatments by neutralizing the antibodies induced in vivo is also disclosed.

The present invention is directed to compositions and methods for the treatment of diseases comprising the administration of compositions comprising one or more peptide(s) having a stimulatory effect on the afflicted host's immune system. Specifically, the invention relates to methods comprising the use of cationic amphipathic peptides having an alpha-helical structure and effecting activation of macrophages when administered in a therapeutically sufficient amount. The methods of the present invention are useful for the treatment of, for example, infectious diseases or cancer.

The inventions provide compositions and methods for nucleic acid delivery comprising IIPMA conjugated to a polyamine. These compositions have the benefit of the steric hindrance of HPMA and the nucleic acid binding capability of a polyamine. Useful polyamines for this purpose include spermine, spermidine and their analogues, and DFMO. These polyamines have the ability not only to bind nucleic acids, but also have anti-cancer effects themselves. The compounds provided can also include ligand binding domains, such as vascular endothelial growth factors, somatostatin and somatostatin analogs, transferring, melanotropin, ApoE and ApoE peptides, von Willebrand's factor and von Willebrand's factor peptides, adenoviral fiber protein and adenoviral fiber protein peptides, PD 1 and PD 1 peptides, EGF and EGF peptides, RGD peptides, CCK peptides, antibody and antibody fragments, folate, pyridoxyl and sialyl-LewisX and chemical analogs. Methods for using these compositions to achieve a therapeutic effect, including for vaccination, are also provided.

The present invention is drawn to immunotherapeutic methods to treat tumors / cancers that produce progastrin ectopically or are dependent on progastrin for their growth. Disclosed herein are immunogenic compositions comprising agents that target progastrin, agents that target the progastrin receptor, annexin II, or both. Such a composition may be administered in combination with chemotherapy or to an individual who had been previously subjected to chemotherapy or radiation therapy. The cancers that may be treated using such a composition may include but are not limited to colon cancer, breast cancer, lung cancer or pancreatic cancer.