Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/28—Compounds containing heavy metals
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P39/00—General protective or antinoxious agents
  • A61P39/06—Free radical scavengers or antioxidants
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P9/00—Drugs for disorders of the cardiovascular system
  • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
  • C07C251/02—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups
  • C07C251/24—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to carbon atoms of six-membered aromatic rings
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
  • C07F13/00—Compounds containing elements of Groups 7 or 17 of the Periodic Table
  • C07F13/005—Compounds without a metal-carbon linkage
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
  • A61K2800/52—Stabilizers
  • A61K2800/522—Antioxidants; Radical scavengers
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
  • A61K2800/58—Metal complex; Coordination compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses

Definitions

• compositions and methods of the invention are also useful for chemoprevention of chemical carcinogenesis and alteration of drug metabolism involving epoxide or free oxygen radical intermediates.
• ovothiols which are mercaptohistidine derivatives, also decompose peroxides nonenzymatically.
• ROS pathological conditions
• ROS are generated by activated phagocytic leukocytes; for example, during the neutrophil "respiratory burst", superoxide anion is generated by the membrane-bound NADPH oxidase.
• ROS are also believed to accumulate when tissues are subjected to ischemia followed by reperfusion.
• malondialdehyde is a reaction product of peroxidized lipids that reacts with virtually any amine-containing
• antioxidants In an effort to prevent the damaging effects of oxyradical formation during reoxygenation of ischemic tissues, a variety of antioxidants have been used.
• One strategy for preventing oxyradical-induced damage is to inhibit the formation of oxyradicals such as superoxide.
• Iron ion chelators such as desferrioxamine (also called deferoxamine or Desferol) and others, inhibit iron ion- dependent «OH generation and thus act as inhibitors of free radical formation (Gutteridge et al. (1979) Biochem. J. 184: 469; Halliwell B (1989) Free Radical Biol. Med. 7: 645; Van der Kraaij et al. (1989) Circulation 80: 158).
• Amino-steroid- based antioxidants such as the 21-aminosteroids termed
• Another strategy for preventing oxyradical-induced damage is to catalytically remove oxyradicals such as
• desferroxamine and manganese has SOD activity and has shown some activity in biological models but the instability of the metal ligand complex apparently precludes its pharmaceutical use. Porphyrin-manganese complexes have been shown to protect bacteria from paraquat toxicity and to promote the aerobic survival of SOD-deficient E. coli mutants.
• the polymers are usually formed by reactions of unsaturated hydrocarbons, although any hydrocarbon can polymerize. Generally, olefins tend to polymerize more readily than aromatics, which in turn
• compositions possess the activity of
• pharmaceutical agent or drug refers to a chemical compound or composition capable of inducing a desired therapeutic effect when properly
• quaternary amine refers to the positively charged group -N + R , R ,, R"', where R', R", and R'" are independently selected and are alkyl or aryl.
• a preferred amino group is -NH 2 .
• blocking groups for substitution at any of R 1 , R 2 , R 3 and R 4 .
• the blocking groups selected are
• Y 1 and Y 4 are examples of substituents independently selected from the group consisting of hydrogen, halides, alkyls, aryls, alkoxy groups, substituted alkoxy groups, nitro groups, and amino groups.
• substituents independently selected from the group consisting of hydrogen, halides, alkyls, aryls, alkoxy groups, substituted alkoxy groups, nitro groups, and amino groups.
• Y 1 and Y 4 are examples of substituents independently selected from the group consisting of hydrogen, halides, alkyls, aryls, alkoxy groups, substituted alkoxy groups, nitro groups, and amino groups.
• the salen-transition metal has the following structure: where M is a transition metal ion, typically Mn, and A is an anion, typically Cl; where n is either 4, 5, or 6; where X 1 , X 2 , X 3 , and X 4 are independently selected from the group consisting of aryls, arylalkyls, aryloxys, primary alkyls, secondary alkyls, tertiary alkyls, alkoxy, substituted alkoxy, heteroatoms, aminos, quaternary amines, and hydrogen;
• salicylaldehyde derivative a derivative-based complex of a transition metal ion.
• solden is used herein to refer to those ligands typically formed through a condensation reaction of two molecules of a salicylaldehyde derivative with one molecule of a diamine derivative. While salen ligands are formed from
• reaction mixture is heated to reflux for 1 h and then 1.0 mmol of Mn(Oac) 2 ⁇ 4H 2 O is added in one portion to the hot (60°C) solution.
• the color of the solution immediately turns from yellow to brown upon addition. It is refluxed for an additional 30 min and then cooled to room temperature.
• a solution of 10% NaCl (5ml) is then added dropwise and the mixture stirred for 0.5h. The solvents are then removed in vacuo and the residue is
• compositions comprising an antioxidant salen-transition metal complex of the present invention are useful for topical and parenteral
• concentration of the antioxidant salen-transition metal complex(es) in these formulations can vary widely, i.e., from less than about 1 nM, usually at least about O.1mM to as much as 100 mM and will be selected primarily based on fluid volumes, viscosities, etc., in accordance with the particular mode of administration selected. Most usually, the
• compositions comprising such carriers are
• celluloses glucose, sucrose, magnesium carbonate, and the like may be used.
• the active compound as defined above may be formulated as suppositories using, for example, triglycerides, for example, the Witepsols, as the carrier.
• reactive oxygen species can be used to advantage to inhibit or slow damage to biological tissues and cells.
• benzoyl peroxide is a widely used treatment for acne lesions; excessive or inappropriate application of benzoyl peroxide (e.g., accidental application to the eyes) may be treated by local (or if desired, systemic) administration of an
• Antioxidant salen-transition metal complexes typically antioxidant salen-Mn complexes, such as compound C7, are used to protect cells and tissues from free radical- producing agents, such as ionizing radiation and
• a solution of an antioxidant salen- metal complex can be encapsulated in micelles to form
• Antioxidant salen-metal complexes may also be administered to deep-divers or individuals exposed to
• an efficacious dose of an antioxidant salen-metal complex to an individual may permit the breathing or hyberbaric and/or oxygen-enriched gases with a reduced risk of oxygen toxicity. It is also believed that administration of an efficacious dosage of an antioxidant salen-metal complex can reduced toxicity and biological damage associated with exposure to ozone. Prophylactic administration of an
• emollients include the following:
• Ethoxylated glycerides such as ethoxylated glyceryl monostearate.
• Fatty alcohols having 10 to 20 carbon atoms Lauryl, myristyl, cetyl, hexadecyl, stearyl, isostearyl,
• poly-fatty acid esters ethoxylated glyceryl monostearate, 1,3-butylene glycol monostearate, 1,3-butylene glycol
• Preferred skin conditioning agents are the propoxylated glycerol derivatives.
• LVDP Left Ventricular Developed Pressure
• MPTP in mice were administered two injections of MPTP dissolved in normal saline (40 mg/kg, s.c.) 24 hours apart. A group of animals also received C7 in three injections (33 mg/kg, s.c.) administered 24 hours apart, starting 1 day before the onset of MPTP treatment. Animals were sacrificed 7 days after the first MPTP injection, and neuronal pathology was assessed by the binding of 3 H-mazindol, a ligand for the dopamine transporter, to 10 mm frozen brain sections or to striatal homogenates.
• Fig. 10 shows I.e.v. injection of 6-OHDA (50 ⁇ g) resulted in a 60-70% decrease in mazindol binding in

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• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Organic Chemistry (AREA)
• General Health & Medical Sciences (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• Animal Behavior & Ethology (AREA)
• Pharmacology & Pharmacy (AREA)
• Medicinal Chemistry (AREA)
• Epidemiology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• General Chemical & Material Sciences (AREA)
• Engineering & Computer Science (AREA)
• Birds (AREA)
• Dermatology (AREA)
• Vascular Medicine (AREA)
• Neurosurgery (AREA)
• Toxicology (AREA)
• Heart & Thoracic Surgery (AREA)
• Cardiology (AREA)
• Biomedical Technology (AREA)
• Neurology (AREA)
• Biochemistry (AREA)
• Urology & Nephrology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Cosmetics (AREA)
• Anti-Oxidant Or Stabilizer Compositions (AREA)
• Compositions Of Macromolecular Compounds (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

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• 1995
  • 1995-06-07 US US08/485,489 patent/US5696109A/en not_active Expired - Lifetime
• 1996
  • 1996-06-06 WO PCT/US1996/010037 patent/WO1996040148A1/en not_active Ceased
  • 1996-06-06 AU AU63328/96A patent/AU719450B2/en not_active Ceased
  • 1996-06-06 EP EP96922461A patent/EP0831836A4/en not_active Withdrawn
  • 1996-06-06 AU AU62725/96A patent/AU6272596A/en not_active Abandoned
  • 1996-06-06 CA CA002223510A patent/CA2223510C/en not_active Expired - Fee Related
  • 1996-06-06 WO PCT/US1996/010267 patent/WO1996040149A1/en not_active Ceased
  • 1996-06-06 JP JP50227297A patent/JP4160115B2/ja not_active Expired - Fee Related
  • 1996-06-06 US US08/973,577 patent/US6046188A/en not_active Expired - Fee Related
• 2000
  • 2000-04-04 US US09/542,182 patent/US6573257B2/en not_active Expired - Fee Related
• 2003
  • 2003-05-30 US US10/452,695 patent/US6900198B2/en not_active Expired - Fee Related
• 2005
  • 2005-05-27 US US11/139,141 patent/US20050249796A1/en not_active Abandoned
• 2008
  • 2008-12-11 US US12/332,989 patent/US20090311230A1/en not_active Abandoned

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