47 results about "Adrenomedullin" patented technology

The present invention provides methods of preventing organ destruction and shut-down due to shock in a patient suffering from sepsis or at risk for sepsis, comprising administering adrenomedullin and adrenomedullin binding protein-1 to the patient. Also provided are compositions containing adrenomedullin and adrenomedullin binding protein-1 or precursors, in a pharmaceutically acceptable carrier.

Methods of treating a mammal in shock or at risk for shock are provided. The methods involve administration of an adrenomedullin binding protein-1 to the mammal. Also provided are methods of preventing or treating a physiologic effect of shock in a mammal. These methods also involve administration of an adrenomedullin binding protein-1 to the mammal.

The present invention provides methods for the isolation, identification, and purification of adrenomedullin (AM)-binding proteins. Also, provided are methods for utilizing the purified AM-binding proteins, or functional portions thereof, to diagnose, treat, and monitor AM-related diseases, for example, diseases or disorders associated with abnormally elevated AM levels. In addition, the present invention provides a newly identified complex between AM and a specific AM-binding protein 1 (AMBP-1); which has been isolated and identified herein as factor H (fH). The invention also provides AM / AMBP complexes, particularly AM / FH complexes, and antibodies specifically reactive with this complexes. Further provided are methods for identifying and purifying complexes of AM and an AM binding protein using anti-AM / fH antibodies, and methods for treating conditions such as cancer or diabetes utilizing compositions comprising these antibodies. The present invention additionally provides methods for identifying antagonists agents that inhibit the function of AM, factor H, or the AM / factor H complex. The invention also provides methods for treating conditions such as cancer or diabetes using these antagonist agents.

An object of the present invention is to provide methods for preventing or treating a steroid-resistant or steroid-dependent inflammatory bowel disease. The object can be achieved by a method for preventing or treating a steroid-resistant or steroid-dependent inflammatory bowel disease in a patient in need of the prevention or treatment of the inflammatory bowel disease, comprises administering an effective amount of adrenomedullin, a modified product thereof having an activity of suppressing steroid-resistant or steroid-dependent inflammation, or a salt thereof having an activity of suppressing steroid-resistant or steroid-dependent inflammation, to the patient.

Subject matter of the present disclosure is an anti-adrenomedullin antibody or an anti-adrenomedullin antibody fragment or anti-ADM non-Ig scaffold wherein said antibody or said fragment or scaffold is a non-neutralizing antibody, antibody fragment or non-Ig scaffold, respectively. Subject matter of the present disclosure is also an anti-adrenomedullin antibody or an anti-adrenomedullin antibody fragment or anti-ADM non-Ig scaffold for use in a treatment of a chronic or acute disease wherein said antibody or fragment or scaffold is: —� an ADM stabilizing antibody or an adrenomedullin stabilizing antibody fragment or an ADM stabilizing non-Ig scaffold that enhances the t 1 / 2 half retention time of adrenomedullin in serum, blood, plasma at least 10 %, preferably at least, 50 %, more preferably >50 %, most preferably 100 % and / or —� wherein said anti-ADM antibody or an anti-adrenomedullin antibody fragment or anti-ADM non-Ig scaffold blocks the bioactivity of ADM to not more than 80 %, or not more than 50 %.

This invention relates, e.g., to methods for inhibiting or stimulating an activity of an adrenomedullin (AM) or gastrin releasing peptide (GRP) peptide hormone, comprising contacting the peptide with a small molecule, non-peptide, modulatory agent of the invention. Complexes of these modulatory agents with other components, such as the peptides or blocking antibodies specific for the peptides, are also described, as are pharmaceutical compositions comprising the modulatory agents, and methods for using the modulatory agents to diagnose or treat patients.

Pharmaceutical compositions containing adrenomedullin antagonist peptides, DNA, RNA compounds inhibitory on adrenomedullin activity, resulting in the efficient blockade of the induction of macroangiogenesis or vasculogenesis of more than 8 μm (in case of murine models), suppress the proliferation of cancer cells due to that inhibitory effect and suppress the protective activity of adrenomedullin. Accordingly, the pharmaceutical compositions of the present invention described herein can be used to treat various cancers, including, but not limited to, stomach cancer, colorectal cancer, lung cancer, ovarian cancer, liver cancer, and pancreatic cancer. Pharmaceutical compositions containing adrenomedullin expression vectors described herein induce macroangiogenesis and, accordingly are effective in treating cardiovascular and renal diseases such as congestive heart failure, myocardial infarction, hypertension, chronic renal failure, stroke, diabetes mellitus, and septic shock.

The invention relates to a platelet preserving agent, which has the following constituents (by weight percent): dipotassium EDTA: 10-14%, sodium citrate: 6-10%, Novocain:0.45-0.55%, Polyvinylpyrrolidone: 0.46-0.50%, polyethyleneglycol 6000: 0.48-0.52%, adenosine triphosphate: 0.03-0.07%, heparan: 0.005-0.015%, prostacyclin: 0.005-0.015%, urokinase: 0.01-0.03%, plasmin: 0.005-0.015%, adrenomedullin: 0.01-0.03%, hydroxyethyl cellulose sodium: 0.15-0.25%, JNSO-2000 long-acting antimicrobial agent: 0.05-0.15%, and water: the residual amount. The platelet preserving agent preparation method provided by the invention has the following steps in sequence: proportioning main raw materials and performing ultrasonic wave action, adding protein material liable to lose the activity and uniformly mixing, performing suction filtration and preparing. The platelet preserving agent provided by the invention enables platelets to maintain the stable state of individual distribution within 24 hours after leaving the body and have no statistical variation within 24 hours, thereby ensuring the accuracy in blood cell analysis. The platelet preserving agent preparation method provided by the invention has the remarkable implementation effect contrasted and verified by testing.

The present invention relates to an adrenomedullin derivative including an adrenomedullin peptide, or a fragment thereof chelated or otherwise bound to at least one active agent. Examples of active agents include a paramagnetic element, a radioactive element and a fibrinolytic agent, among others. Paramagnetic agents have a distribution that is relatively easily shown through Magnetic Resonance Imaging (MRI). Radioactive agents have applications in imaging and delivery of radiations, depending on the specific element included in the active agent. Delivery of fibrinolytic agents mainly to a specific organ, such as for example to the lungs, allows to substantially improve the specificity and efficacy of thrombolytic therapy by allowing local delivery of the fibrinolytic agent, thereby reducing the risks of major bleeding in the therapy of the organ. If the organ is the lungs, a non-limiting example of pathology treatable with the fibrinolytic agent is pulmonary embolus.

A composition for inhibiting spontaneous myometrial contraction or bradykinin-induced contraction, comprising adrenomedullin. The composition of the present invention may be used to selectively inhibit spontaneous myometrial contraction or bradykinin-induced contraction to prevent premature labor, prevent miscarriage, arrest parturition prior to cesarean section, or to treat dysmenorrhea.

A medicinal composition for suppressing or preventing the metastasis of a malignant tumor, the composition comprising, as an active ingredient, at least one kind of vasoprotective agent selected from the following (i) to (iv): (i) angiotensin II receptor antagonist, (ii) HMG-CoA reductase inhibitor, (iii) ghrelin or its derivative, and (iv) adrenomedullin or its derivative; or a pharmacologically acceptable salt thereof.

The present invention discloses solid phase synthesis process of adrenal medullarin (27-52). The synthesis process includes the first solid phase Fmoc polypeptide synthesis to graft protective amino acid Fmoc-Ala-OH onto resin, connecting the rest protective amino acids successively, cutting down the synthesized coarse peptide with peptide cutting reagent, and final separating and purifying to obtain the adrenal medullarin (27-52) as the target peptide. The present invention has mild reaction condition, high reaction rate, less side reactions, easy purification, high yield, no corrosion to the equipment and no environmental pollution.

Methods of treating a mammal at risk for ischemia-reperfusion injury are provided. The methods comprise administering an adrenomedullin binding protein-1 (AMBP-1) to the mammal in sufficient amount to reduce the injury. Also provided are methods of treating a mammal at risk for ischemia-reperfusion injury to the bowel. The methods comprise administering adrenomedullin to the mammal in sufficient amount to reduce the injury.

We claim a method of treating a patient to stimulate chondrocyte proliferation comprising administering to said patient an adrenomedullin analog that is adrenomedullin-(27–52) wherein said patient is suffering from cartilage disorders, and a method of stimulating chondrocyte proliferation comprising administering to chondrocyte cells adrenomedullin-(27–52).

Methods of treating a mammal in shock or at risk for shock are provided. The methods involve administration of an adrenomedullin binding protein-1 to the mammal. Also provided are methods of preventing or treating a physiologic effect of shock in a mammal. These methods also involve administration of an adrenomedullin binding protein-1 to the mammal.

The present invention relates to an adrenomedullin derivative including an adrenomedullin peptide, or a fragment thereof chelated or otherwise bound to at least one active agent. Examples of active agents include a paramagnetic element, a radioactive element and a fibrinolytic agent, among others. Paramagnetic agents have a distribution that is relatively easily shown through Magnetic Resonance Imaging (MRI). Radioactive agents have applications in imaging and delivery of radiations, depending on the specific element included in the active agent. Delivery of fibrinolytic agents mainly to a specific organ, such as for example to the lungs, allows to substantially improve the specificity and efficacy of thrombolytic therapy by allowing local delivery of the fibrinolytic agent, thereby reducing the risks of major bleeding in the therapy of the organ. If the organ is the lungs, a non-limiting example of pathology treatable with the fibrinolytic agent is pulmonary embolus.

The present invention relates to an adrenomedullin derivative including an adrenomedullin peptide chelated with at least one active agent. Examples of active agents include a paramagnetic element, a radioactive element and a fibrinolytic agent, among others. Paramagnetic agents have a distribution that is relatively easily shown through Magnetic Resonance Imaging (MRI). Radioactive agents have applications in imaging and delivery of radiations, depending on the specific element included in the active agent. Delivery of fibrinolytic agents mainly to a specific organ, such us for example to the lungs, allows to substantially improve the specificity and efficacy of thrombolytic therapy by allowing local delivery of the fibrinolytic agent, thereby reducing the risks of major bleeding in the therapy of the organ. If the organ is the lungs, a non-limiting example of pathology treatable with the fibrinolytic is pulmonary embolus.

An objective of the present invention is to provide methods for producing progenitor cells which show a high proliferation ability ex vivo and promote neovascularization or myocardium regeneration, by culturing pluripotent cells in a medium containing adrenomedullin (AM) and / or vascular endothelial growth factor (VEGF). Moreover, another objective of the present invention is to provide the progenitor cells and uses thereof. In order to solve the above problems, the inventors of the present application have successfully developed a novel culture technique for producing progenitor cells from adipose tissues more efficiently compared to the conventional techniques, by using adrenomedullin (AM) and / or vascular endothelial growth factor (VEGF). The progenitor cells produced by the present inventors are specialized cells having a potent proliferation ability, a revascularization ability, and a myocardium regeneration ability, and have the property of not differentiating into adipocytes even if subjected to differentiation induction into adipocytes. Therefore, the progenitor cells of the present invention can be effective pharmaceutical agents for intractable diseases in the brain, lung, liver, kidney and the like.

Methods of treating a mammal at risk for ischemia-reperfusion injury are provided. The methods comprise administering an adrenomedullin binding protein-1 (AMBP-1) to the mammal in sufficient amount to reduce the injury. Also provided are methods of treating a mammal at risk for ischemia-reperfusion injury to the bowel. The methods comprise administering adrenomedullin to the mammal in sufficient amount to reduce the injury.

Methods of treating a mammal at risk for ischemia-reperfusion injury are provided. The methods comprise administrating an adrenomedullin binding protein-1 (AMBP-1) to the mammal in sufficient amount to reduce the injury. Also provided are methods of treating a mammal at risk for ischemia-reperfusion injury to the bowel. The methods comprise administering adrenomedullin to the mammal in sufficient amount to reduce the injury.

A composition for inhibiting spontaneous myometrial contraction or bradykinin-induced contraction, comprising adrenomedullin. The composition of the present invention may be used to selectively inhibit spontaneous myometrial contraction or bradykinin-induced contraction to prevent premature labor, prevent miscarriage, arrest parturition prior to cesarean section, or to treat dysmenorrhea.

[Problems to be Solved] An objective of the present invention is to provide methods for regenerating or repairing damaged tissues using adrenomedullin. Another objective is to provide pharmaceutical agents that comprise adrenomedullin as an active ingredient for regenerating or repairing damaged tissues.[Means for Solving the Problems] To solve the above problems, the present inventors administered adrenomedullin (hereinafter indicated as AM) or physiological saline to C57BL / 6 mice, and counted the numbers of mononuclear cells and Sca-1-positive cells in the blood. The result showed that AM increased the numbers of mononuclear cells and stem cell antigen-1-positive cells in the blood. It was also shown that by administering AM to a mouse model of pulmonary emphysema and a rat model of acute myocardial infarction, the quantity of bone marrow-derived cells that migrated and settled into the damaged tissues increased, and the recruited bone marrow cells differentiated into blood vessels, alveoli, and cardiac muscle at the lesion sites. Further, decrease in infarct size, suppression of the enlargement of alveolar diameter, and improvement of organ functions were confirmed in the models of myocardial infarction and pulmonary emphysema.

An object of the present invention is to provide methods for preventing or treating a steroid-resistant or steroid-dependent inflammatory bowel disease. The object can be achieved by a method for preventing or treating a steroid-resistant or steroid-dependent inflammatory bowel disease in a patient in need of the prevention or treatment of the inflammatory bowel disease, comprises administering an effective amount of adrenomedullin, a modified product thereof having an activity of suppressing steroid-resistant or steroid-dependent inflammation, or a salt thereof having an activity of suppressing steroid-resistant or steroid-dependent inflammation, to the patient.

Subject matter of the present invention is an anti-Adrenomedullin (ADM) antibody or an anti-Adrenomedullin antibody fragment or an anti-ADM non-lg scaffold for use in intervention and therapy of congestion in a patient in need thereof.

The present invention discloses solid phase synthesis process of adrenal medullarin (27-52). The synthesis process includes the first solid phase Fmoc polypeptide synthesis to graft protective amino acid Fmoc-Ala-OH onto resin, connecting the rest protective amino acids successively, cutting down the synthesized coarse peptide with peptide cutting reagent, and final separating and purifying to obtain the adrenal medullarin (27-52) as the target peptide. The present invention has mild reaction condition, high reaction rate, less side reactions, easy purification, high yield, no corrosion to the equipment and no environmental pollution.

The present invention relates to methods of improving blastocyst implantation by delivering adrenomedullin to the endometrium of a subject. The invention further relates to methods of performing in vitro fertilization.