100 results about "Nitrosylation" patented technology

Disclosed are novel polymers derivatized with at least one —NO_x group per 1200 atomic mass unit of the polymer. X is one or two. In one embodiment, the polymer is an S-nitrosylated polymer and is prepared by reacting a polythiolated polymer with a nitrosylating agent under conditions suitable for nitrosylating free thiol groups. The polymers of the present invention can be used to coat medical devices to deliver nitric oxide in vivo to treatment sites.

A C-nitroso compound having a molecular weight ranging from about 225 to about 1,000 (from about 225 to about 600 for oral administration) on a monomeric basis wherein a nitroso group is attached to a tertiary carbon, which is obtained by nitrosylation of a carbon acid having a pKa less than about 25, is useful as an NO donor. In another case, the C-nitroso compound contains the moiety

—C—N(O)X—

where X is S, O or NR. One embodiment is directed to COX-2 inhibitors where a tertiary carbon atom and/or an oxygen atom and/or a sulfur atom is nitrosylated.

A C-nitroso compound having a molecular weight ranging from 225 to 1,000 (from 225 to 600 for oral administration) on a monomeric basis wherein a nitroso group is attached to a tertiary carbon, which is obtained by nitrosylation of a carbon acid having a pKa less than about 25, is useful as an NO donor. When the compound is obtained from a carbon acid with a pKa less than about 10, it provides vascular relaxing effect when used at micromolar concentrations and this activity is potentiated by glutathione to be obtained at nanomolar concentrations. When the compound is obtained from a carbon acid with a pKa ranging from about 15 to about 20, vascular relaxing effect is obtained at nanomolar concentrations without glutathione. In another embodiment, a biocompatible polymer incorporates a C-nitroso moiety.

The invention describes novel nitrosated and/or nitrosylated compounds of the invention, and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated compound of the invention, and, optionally, at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one compound of the invention, that is optionally nitrosated and/or nitrosylated, and at least one nitric oxide donor compound and/or at least one therapeutic agent. The compounds and compositions of the invention can also be bound to a matrix. The invention also provides methods for treating cardiovascular diseases, for inhibiting platelet aggregation and platelet adhesion caused by the exposure of blood to a medical device, for treating pathological conditions resulting from abnormal cell proliferation; transplantation rejections, autoimmune, inflammatory, proliferative, hyperproliferative or vascular diseases; for reducing scar tissue or for inhibiting wound contraction, particularly the prophylactic and/or therapeutic treatment of restenosis by administering at least one compound of the invention that is optionally nitrosated and/or nitrosylated, in combination with nitric oxide donors that are capable of releasing nitric oxide or indirectly delivering or transferring nitric oxide to targeted sites under physiological conditions. The compounds of the invention are preferably estradiol compounds, troglitazone compounds, tranilast compounds, retinoic acid compounds, resveratol compounds, myophenolic acid compounds, acid compounds, anthracenone compounds and trapidil compounds.

The present invention describes novel nitrosated and/or nitrosylated α-adrenergic receptor antagonists, and novel compositions containing at least one nitrosated and/or nitrosylated α-adrenergic receptor antagonist, and, optionally, one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or are a substrate for nitric oxide synthase, and/or one or more vasoactive agents. The present invention also provides novel compositions containing at least one α-adrenergic receptor antagonist, and one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing benign prostatic hyperplasia, hypertension, congestive heart failure, variant (Printzmetal) angina, glaucoma, neurodegenerative disorders, vasospastic diseases, cognitive disorders, urge incontinence, or overactive bladder, and for reversing the state of anesthesia.

This invention pertains generally to the field of chemical synthesis and purification, and more specifically to methods of synthesizing and purifying certain 3,7-diaminophenothiazin-5-ium compounds (referred to herein as “diaminophenothiazinium compounds”) including Methythioninium Chloride (MTC) (also known as Methylene Blue). In one embodiment, the method comprises the steps of, in order: nitrosylation (NOS); nitrosyl reduction (NR); thiosulfonic acid formation (TSAF); oxidative coupling (OC); Cr(VI) reduction (CR); isolation and purification of zwitterionic intermediate (IAPOZI); ring closure (RC); chloride salt formation (CSF); one of: sulphide treatment (ST); dimethyldithiocarbamate treatment (DT); carbonate treatment (CT); ethylenediaminetetraacetic acid treatment (EDTAT); organic extraction (OE); and recrystallisation (RX). The present invention also pertains to the resulting (high purity) compounds, compositions comprising them (e.g., tablets, capsules), and their use in methods of inactivating pathogens, and methods of medical treatment and diagnosis, etc., for example, for tauopathies, Alzheimer's disease (AD), skin cancer, melanoma, viral diseases, bacterial diseases, or protozoal diseases.

The present invention describes novel nitrosated and/or nitrosylated potassium channel activators, and novel compositions comprising at least one nitrosated and/or nitrosylated potassium channel activator, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one vasoactive agent. The present invention also provides novel compositions comprising at least one potassium channel activator, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one vasoactive agent. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing cardiovascular disorders, cerebrovascular disorders, hypertension, asthma, baldness, urinary incontinence, epilepsy, sleep disorders, gastrointestinal disorders, migraines, irritable bowel syndrome and sensitive skin.

The invention describes novel nitrosated and/or nitrosylated rapamycin compounds, and novel compositions comprising at least one nitrosated and/or nitrosylated rapamycin compound, and, optionally, at least one nitric oxide donor compound. The invention also provides novel compositions comprising at least one rapamycin compound and at least one nitric oxide donor compound and/or at least one therapeutic agent. The compounds and compositions of the invention can also be bound to a matrix. The invention also provides methods for treating and/or preventing cardiovascular diseases, for the prevention of platelet aggregation and platelet adhesion caused by the exposure of blood to a medical device, for treating and/or preventing pathological conditions resulting from abnormal cell proliferation; transplantation rejections; autoimmune, inflammatory, proliferative, hyperproliferative or vascular diseases; for reducing scar tissue or for inhibiting wound contraction, particularly the prophylactic and/or therapeutic treatment of restenosis by administering nitrosated and/or nitrosylated rapamycin compounds or rapamycin compounds in combination with nitric oxide donors that are capable of releasing nitric oxide or indirectly delivering or transferring nitric oxide to targeted sites under physiological conditions.

The present invention relates to providing novel therapeutics for treating diabetes other glycemic disorders. Such therapeutics involve the signaling pathways that contribute to regulation of glucose-stimulated insulin secretion. Of particular interest are modulators of a key component in the glucokinase pathway. Thus, the present provides methods of screening for modulators of glucokinase activity, expression, translocation, conformation, nitrosylation and interaction with other molecules as useful target for pharmacological manipulation in the treatment of diabetes and other glycemic disorders.

The invention is directed to nitrosated or nitrosylated alpha-adrenergic receptor antagonists, compositions comprising alpha-adrenergic receptor antagonists that are optionally substituted with at least one NO or NO₂ moiety and compounds that donate, transfer or release nitric oxide or elevate levels of endogenous endothelium-derived relaxing factor, and methods for treating sexual dysfunctions in males and females. The invention also provides methods for treating female sexual dysfunctions by administering S-nitrosothiol compounds.

The invention describes novel cyclooxygenase 2 (COX-2) selective inhibitors having at least one oxime group or hydrazone group and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor having at least one oxime group or hydrazone group, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor having at least one oxime group or hydrazone group, optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention having at least one oxime group or hydrazone group can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal and/or respiratory toxicity; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

Nitrosylation of proteins and amino acid groups enables selective regulation of protein function, and also endows the proteins and amino acids with additional smooth muscle relaxant and platelet inhibitory capabilities. Thus, the invention relates to novel compounds achieved by nitrosylation of protein thiols. Such compounds include: S-nitroso-t-PA, S-nitroso-cathepsin; S-nitroso-lipoprotein; and S-nitroso-immunoglobulin. The invention also relates to therapeutic use of S-nitroso-protein compounds for regulating protein function, cellular metabolism and effecting vasodilation, platelet inhibition, relaxation of non-vascular smooth muscle, and increasing blood oxygen transport by hemoglobin and myoglobin. The compounds are also used to deliver nitric oxide in its most bioactive form in order to achieve the effects described above, or for in vitro nitrosylation of molecules present in the body. The invention also relates to the nitrosylation of oxygen, carbon and nitrogen moieties present on proteins and amino acids, and the use thereof to achieve the above physiological effects.

The present invention provides a nitrosylated albumin variant wherein one or more amino acid residues of constituent amino acid sequences are substituted, or a different amino acid residue is inserted into a part of the constituent amino acid sequences. The albumin variant has sufficient antimicrobial property and permits application as various useful pharmaceutical compositions.

The invention describes novel cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal and/or respiratory toxicity; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

The invention discloses a keratin biomacromolecular nitric oxide donor. The keratin biomacromolecular nitric oxide donor contains reduced keratin obtained through reduction treatment on keratin, and SNO groups are formed on the sulfydryl groups of the reduced keratin. The keratin biomacromolecular nitric oxide donor is an S-nitrosated keratin and is synthesized and prepared through reaction between the reduced kertin and tert-butyl nitrite or sodium nitrite. The keratin biomacromolecular nitric oxide donor is high in molecular weight, stable in storage and capable of releasing nitric oxide under certain conditions. The keratin biomacromolecular nitric oxide donor can directly serve as a nitric oxide donor as well as be compounded with other polymers to prepare nitric oxide releasing materials to give play to a controllable nitric oxide releasing function, thereby being applicable to preparing materials such as artificial blood vessels, intravascular stent and wound dressings.

The invention relates to a new method for treating nitrogen oxide waste gas. The new method for treating the nitrogen oxide waste gas comprises three key links, namely efficient absorption of an organic solvent, catalytic oxidation and subsequent water extraction, wherein the organic solvent is a mixed organic solvent mainly comprising one or more esters, alcohols and ketones; nitrogen monoxide and oxygen which are absorbed by the organic solvent are oxidized into nitrogen dioxide and dinitrogen trioxide under the catalytic action of a rare earth complex, and then water extraction is carried out, so as to obtain an aqueous solution of dinitrogen trioxide, nitrous acid and nitric acid; the aqueous solution can be applied to a nitration and nitrosylation reaction or be recycled as an oxidizing agent, and the organic solvent can be recycled and applied to absorption of nitrogen monoxide; the rare earth complex has the catalytic oxidation function and is formed by rare earth and a phenolic ester compound, and complexing capacity of the rare earth complex is approximate to that of rare earth and nitrogen oxide. The new method for treating the nitrogen oxide waste gas is applicable to absorption, conversion and utilization of low-concentration nitrogen oxide, and harm to the environment owning to emission of waste gas is eliminated.

The present invention, in some aspects, relates to systems and methods for determining oxidized proteins, including nitrosylated proteins such as S-nitrosylated proteins. The systems and methods of the invention can be used in vitro (e.g., in cell or tissue culture) or in vivo. For instance, in some cases, the invention can be used to spatially determine the location and/or concentration of oxidized proteins within cells and/or tissues (e.g., through visual detection). In one set of embodiments, a nitrosylated or otherwise oxidized moiety on a protein may be reacted with a detection entity, which may be, for example, fluorescent, radioactive, electron-dense, able to bind to a signaling entity or a binding partner in order to produce a signal, etc. As a specific example, a nitrosothiol moiety on a nitrosylated protein may be reacted with an alkylating agent to form an alkylthio moiety; the alkylthio moiety may include a detection entity or otherwise be able to interact with a signaling entity. In some embodiments, other moieties on the protein may be altered or blocked before reaction of the protein with the detection entity. Such moieties on the protein may be, for instance, non-oxidized or non-nitrosylated moieties able to react with the detection entity. As a particular example, in a protein containing nitrosothiol and (non-nitrosylated) thiol moieties, the thiol moieties may first be altered or blocked prior to reaction of the protein with the detection entity. Also provided in certain aspects of the present invention are kits for determining oxidized proteins, which may include components such as detection entities, alkylating agents, blocking agents, reducing agents, signaling entities, binding partners, antibodies, instructions, and the like.

The invention discloses a small peptide TAT-AVPY for treating ischemic brain damage, and an application thereof. The complete sequence of the small peptide TAT-AVPY is H-YGRKKRRQRRR-AVPY-OH, represented by SEQ ID NO:1. With the small peptide TAT-AVPY provided by the invention, the binding of XIAP and proaspase-9 (Casp 9) can be reduced; nitrosylation of XIAP and proaspase-9 (Casp 9) can be alleviated; and proaspase-9 activation can be alleviated. Therefore, cell apoptosis induced by cerebral ischemia can be alleviated. Also, TAT can directly bring fused small peptide into cells, such that a problem of the approach for the drug to enter cells is solved, and medication is convenient. The small peptide TAT-AVPY has no immunogenicity, and does not cause an immune response of a body. Therefore, side effects are reduced, and the effectiveness of secondary medication or more is ensured.