Abstract: Diacyl-substituted guanidines of the formula I are described where X(1) and X(2) are as defined herein. The compounds are suitable for use as antiarrhythmic pharmaceuticals possessing a cardioprotective component for the prophylaxis and treatment of infarction and for the treatment of angina pectoris, in connection with which they also inhibit or strongly reduce, in a preventitive manner the pathophysiological processes associated with the genesis of ischemically induced damage, in particular associated with the elicitation of ischemically induced cardiac arrhythmias.

Abstract: The present invention relates to a neurotrophic factor secretagogue, in particular, to a BDNF (brain-derived neurotrophic factor) secretagogue, which comprises as an active ingredient an NO donor. The medicament of the present invention promotes the secretion of neurotrophic factors from mammalian central neural cells. Thus, the medicament of the present invention, i.e., NO donor, is possibly applicable to the treatment of diseases caused by neutrotrophic factors, for example, neurodegenerative diseases, and is expected to exhibit the efficacious effects thereon. Also, the present invention provides a novel medication for neurodegenerative diseases.

Abstract: The invention provdes methods of reducing tissue damage resulting from ischemia which comprise administering to a mammal in need of such reduction an effective amount of a combination, or a pharmaceutical composition comprising Such combination, of an NHE-1 inhibitor and a second compound selected from the group consisting of: (a) a complement modulator, (b) a metabolic modulator, (c) an anti-apoptotic agent, (d) a nitric oxide synthase-related agent, and (e) an enzyme/protein modulator.

Abstract: The present invention relates to the treatment of disordered epithelial tissues such as cold sores and other complications resulting from disorders such as herpes, and the like. The invention relates to the use of an anti-infective and/or antimicrobial active agent in a carrier, with vigorous agitation of the disordered epithelial tissue for topical treatment thereof under such conditions sufficient to achieve clinically discernable improvement of the disordered epithelial tissue. The preferred anti-infective and/or antimicrobial active agent is an organohalide such as a quaternary ammonium compound, preferably benzalkonium chloride. The inventive method may be used also in connection with a preferred applicator configuration.

Abstract: Amido polybiguanides and their use as antimicrobial agents in pharmaceutical compositions are disclosed. A method of synthesis of amido polybiguanides is also disclosed. The amido polybiguanides are useful in the preservation of pharmaceutical compositions, particulary opthalmic and otic pharmaceutical compositions and compositions for treating contact lenses. The compounds are especially useful for disinfecting contact lenses.

Abstract: The present invention relates to the treatment of disordered epithelial tissues such as cold sores and other complications resulting from disorders such as herpes, and the like. The invention relates to the use of an anti-infective and/or antimicrobial active agent in a carrier, with vigorous agitation of the disordered epithelial tissue for topical treatment thereof under such conditions sufficient to achieve clinically discernable improvement of the disordered epithelial tissue. The preferred anti-infective and/or antimicrobial active agent is an organohalide such as a quaternary ammonium compound, preferably benzalkonium chloride. The inventive method may be used also in connection with a preferred applicator configuration.

Abstract: Inhibitors of the cellular sodium-hydrogen exchanger are employed for preparing a medicament for preventing age-related functional disorders and dysfuntional changes of organs of the body and for preventing age-related diorders and for prolonging life while maintaining an improved quality of life.

Abstract: A veterinary composition comprising a guanidine derivative, e.g., guanabenz or guanabenz acetate is provided which produces a rapid acting and long lasting sedative and analgesic effect in a subject animal that is selectively reversible. The use of guanabenz in the horse provides for a safe, effective, long lasting and rapidly reversible sedative and analgesic which can be used on the standing animal. Methods of use of the compositions of the invention are also provided.

Abstract: A triple drug therapy, pharmaceutical kit, composition, and method of treatment regimen utilized as a combination of effective amounts of an anxiolytic agent, centrally acting alpha antiadrenergic agent, and central nervous system stimulant for the reduction or prevention of dizziness, drowsiness, depression, delirium, lethargy, mania, orthostatic hypotension, restlessness, weakness in the extremities, and difficulty in being mobile negative side effects caused by therapeutic agents utilized in the treatment of acute and chronic pain syndromes.

Abstract: The present invention provides methods and compositions for enhancing the effect of a neurotrophin on a cell expressing a neurotrophin receptor. The effect is preferably neurotrophin-mediated growth and/or survival, such as neurite growth. The invention employees amphipathic compounds having a hydrophobic membrane-associating face and a hydrophilic face opposed thereto, which preferably mimic the amphipathic domain of the common neurotrophin receptor p75 from amino acid residue 367 to residue 379. Such compounds have charged moieties, polar moieties or combinations that mimic the charged and polar group relationships of p75NTR367-379, and include but are not limited to peptide analogues thereof. The hydrophobic membrane-associating face can interact with a membrane-bound neurotrophin receptor, such as TrkA, and the opposing hydrophillic face can interact with a DNA binding protein, such as nuclear transcription factor NFkB.

Abstract: The present invention relates to the treatment of disordered epithelial tissues such as cold sores and other complications resulting from disorders such as herpes, and the like. The invention relates to the use of an anti-infective and/or antimicrobial active agent in a carrier, with vigorous agitation of the disordered epithelial tissue for topical treatment thereof under such conditions sufficient to achieve clinically discernable improvement of the disordered epithelial tissue. The preferred anti-infective and/or antimicrobial active agent is an organohalide such as a quaternary ammonium compound, preferably benzalkonium chloride. The inventive method may be used also in connection with a preferred applicator configuration.

Abstract: The compositions are aromatic, gaunidino group containing compounds used for inducing anesthesia and reducing core temperatures in mammals.

Abstract: Methods for enhancing the therapeutic and adjuvant use of IL-12 by reducing unwanted transient immunosuppression caused by IL-12 or by high doses thereof involve co-administering IL-12 with an effective amount of an agent that inhibits or neutralizes nitric oxide (NO) in vivo. Enhanced vaccine therapy involves co-administering the IL-12 adjuvant, a selected vaccine antigen and the NO inhibiting/neutralizing agent. Additionally, the toxicity of IL-12 treatment may be reduced by co-administering IL-12 with an effective amount of the NO inhibiting or neutralizing agent. A therapeutic composition characterized by reduced toxicity in mammals contains IL-12, preferably a low dose thereof, and an NO inhibiting or neutralizing agent in a pharmaceutically acceptable carrier. A vaccine composition contains an effective adjuvanting amount of IL-12, an effective amount of an NO inhibiting or neutralizing agent, and an effective protective amount of a vaccine antigen in a pharmaceutically acceptable carrier.

Abstract: Provided are ectoparasite control compositions, a method of controlling an ectoparasite and uses of a composition for controlling an ectoparasite. The ectoparasite control compositions comprise a solvent and 1-methyl-2-nitro-3-[(3-tetrahydrofuryl)methyl]guanidine, wherein said solvent contains mainly N-methyl-2-pyrrolidone. The methods of controlling an ectoparasite, comprise applying to a host animal, an ectoparasite control composition which comprises a solvent and 1-methyl-2-nitro-3-[(3-tetrahydrofuryl)methyl]guanidine, wherein said solvent contains mainly N-methyl-2-pyrrolidone.

Abstract: The present invention relates to an antiseptic composition for treating a human infected with a virus, a bacteria or a fungus, for example, disordered epithelial tissues such as cold sores and other complications resulting from herpes and the like. The composition includes an anti-infective and/or antimicrobial active agent such as benzalkonium chloride in an amount between about 0.1-0.3% by volume (e.g., 0.13%) in a carrier such as an aqueous 70% isopropyl alcohol solution. Application may include vigorous agitation of the disordered epithelial tissue for topical treatment thereof under such conditions sufficient to achieve clinically discernable improvement of the disordered epithelial tissue. The compositions may be used also in connection with specially configured applicators.

Abstract: The present invention relates generally to the non-enzymatic glycosylation of amyloidogenic proteins and the consequent formation of advanced glycosylation endproducts (AGEs). It has been found that formation of AGE-amyloidogenic proteins can enhance amyloidosis. The invention further relates to compositions and methods for the prevention and treatment of amyloidosis associated with amyloid diseases, particularly neurodegenerative disease and Type II diabetes, and more particularly Alzheimer's disease. In a specific example, aggregation of an amyloidogenic peptide, &bgr;AP, is enhanced by the glycosylation reaction of &bgr;AP to form AGE-&bgr;AP as defined herein. Accordingly, the invention extends to a method for modulating the in vivo aggregation of amyloid polypeptides and associated amyloidosis by controlling the formation and presence of AGE-amyloid polypeptide.

Abstract: This invention discloses that a combination of two drugs, from two different and unrelated categories, provides effective and long-lasting relief from neuropathic pain. Both drugs can be taken orally, in a convenient, painless, non-invasive manner that does not require injections. One drug is an aryl-cyclo-alkanolamine (ACAA) which has antagonist (receptor-blocking) activity at the NMDA subclass of glutamate receptors; such drugs include procyclidine, biperiden, and trihexyphenidyl. The other drug is an &agr;2 adrenergic agonist, exemplified by clonidine. When an ACAA drug which blocks NMDA receptors, such as procyclidine, is administered together with an &agr;2 adrenergic agonist such as clonidine, these drugs mutually potentiate one another's neuropathic pain-relieving action, and provide potent and sustained neuropathic pain relief, even when each agent is administered at a low dosage that is below its threshold for causing adverse side effects.

Abstract: The present invention relates generally to mitochondria protecting agents for treating diseases in which mitochondrial dysfunction leads to tissue degeneration and, more specifically, to compounds, compositions and methods related to the same. The methods of this invention involve administration of a pharmaceutically effective amount of a mitochondria protecting agent to a warm-blooded animal in need thereof, and composition of this invention contain a mitochondrial protecting agent in combination with a pharmaceutically acceptable carrier or diluent. Mitochondrial associated diseases which may be treated by the present invention include (but are not limited to) Alzheimer's Disease, diabetes mellitus, Parkinson's Disease, neuronal and cardiac ischemia, Huntington's disease and stroke.

Abstract: The present invention relates generally to mitochondria protecting agents for treating diseases in which mitochondrial dysfunction leads to tissue degeneration and, more specifically, to compounds, compositions and methods related to the same. The methods of this invention involve administration of a pharmaceutically effective amount of a mitochondria protecting agent to a warm-blooded animal in need thereof, and composition of this invention contain a mitochondria protecting agent in combination with a pharmaceutically acceptable carrier or diluent. Mitochondrial associated diseases which may be treated by the present invention include (but are not limited to) Alzheimer's Disease, diabetes mellitus, Parkinson's Disease, neuronal and cardiac ischemia, Huntington's disease and stroke.

Abstract: A process is provided for both removing and controlling biofilms present in industrial cooling and process waters. The process provides a composition which includes the reaction products of an amino base, a formaldehyde, an alkylenepolyamine, and the ammonium salt of an inorganic or organic acid. The composition may be used to remove existing biofilms from process water equipment. Further, lower maintenance dosages may be used to maintain the equipment in a substantially biofilm-free condition.

Abstract: A tryptase inhibitor comprising as an active ingredient at least one member selected from among guanidinoaliphatic acid derivatives of the formula (I), guanidinobenzoic acid derivatives of the formula (II), guanidinophenol derivatives of the formula (III), amidinophenol derivatives of the formula (IV), and novel guanidinophenol derivatives of the formula (V) (in the formulae, Gu is guanidino).

Abstract: Compounds, compositions and methods are disclosed for treating mitochondria-associated diseases, such as cancer, psoriasis, stroke, Alzheimer's Disease and diabetes. The compounds of this invention have structure (I) below, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein Ar and L are as defined herein. The methods of this invention are directed to treating a mitochondria-associated disease by administering to a warm-blooded animal in need thereof an effective amount of a compound of structure (I), typically in the form of a pharmaceutical composition.

Abstract: Compounds of general formula I are disclosed and claimed in the present application, as well as their pharmaceutically acceptable salts, pharmaceutical compositions comprising the novel compounds and their use in therapy, in particular in the management of pain. Intermediates to the compounds of the formula I are also claimed.

Abstract: A combination of two drugs, from two different and previously unrelated categories, provides effective and long-lasting relief from neuropathic pain. Both drugs can be taken orally, in a convenient, painless, non-invasive manner that does not require injections. One drug in this combination is an &agr;2 adrenergic agonist, exemplified by clonidine. The other drug in the combination is an adamantane derivative which has NMDA antagonist activity, such as memantine. Tests described herein demonstrate that when memantine is administered together with an &agr;2 adrenergic agonist such as clonidine, these drugs mutually potentiate one another's neuropathic pain-relieving action, and provide potent and sustained neuropathic pain relief, even when each agent is administered at a low dosage that is below its threshold for causing adverse side effects.

Abstract: A microbiocidal composition including a first component comprises a guanidine compound, a second component which comprises either prochloraz, propiconazole or iodocarb, wherein the weight ratio of first component to second component is in the range of from about 32:1 to about 1:16. The microbiocidal composition provides effective and broader control of micro-organisms in various industrial systems and for household products, agricultural products and biomedical products.

Abstract: A compound selected from the group consisting of a compound of the formula wherein the substituents are defined as set forth in the specification and its salts with non-toxic pharmaceutically acceptable acids and bases useful for treating loss of bone matrix.

Abstract: A composition formulated from a primary anionic surfactant; optionally a secondary surfactant and/or a resin; and a nitrogen-containing compound of the structural formula: wherein R is a saturated, linear, branched or cyclic alkyl or aryl group containing 12 to 22 carbon atoms, with the proviso that R contains at least 80% of a single chain length and R is not lanolin, wheat germ or other natural broad-based chain distribution oil, R1 is a saturated or unsaturated, linear, branched or cyclic alkyl or aryl group containing 1 to 6 carbon atoms and may contain one or more hydroxyl groups, R2 is selected from the group consisting of hydrogen, methyl, ethyl and benzyl; and A− is a monovalent anion.

Abstract: The present invention concerns alkyl aryl carbonyl compounds that possess anti-infective activity. The compounds of the invention can be used to target specific nuclear localization signal, thereby blocking importation of specific proteins or molecular complex into the nucleus of a cell. The invention encompasses methods of use of such compounds for treatment or prevention of infectious diseases, such as parasitic and viral diseases, including, for example, malaria and acquired immunodeficiency syndrome. The use of the compounds to detect certain specific protein structures which are present in nuclear localization sequences is also taught.

Abstract: A method for the treatment and/or prophylaxis of Type II diabetes, which method comprises the administration, to a human or non-human mammal, of an effective non-toxic pharmaceutically acceptable amount of an NO synthase inhibitor, such as aminoguanidine, or a pharmaceutically acceptable derivative thereof.

Abstract: The present invention provides for the use of aminoguanidines for prophylactic and/or therapeutic treatments of undesirable cell growth, e.g. tumors. The present invention provides methods of using aminoguanidines, optionally in combination with a hyperplastic inhibitory agent, to inhibit the growth of undesirable cells in a subject. The present invention is based, at least in part, on the discovery that aminoguanidines inhibit cell growth. The present invention further pertains to compositions for inhibiting undesirable cell growth in a subject. The compositions of the present invention include an effective amount of the aminoguanidine in a pharmaceutically acceptable carrier. Other aspects of the invention include a packaged aminoguanidine. The packaged compound includes instructions for using the aminoguanidine compound for inhibiting undesirable cell growth in a patient or instructions for using the compound in selected quantities, in a pharmaceutically acceptable carrier.

Abstract: The present invention provides therapeutically useful substituted guanidines, and methods of treatment and pharmaceutical compositions that utilize or comprise one or more of such guanidines.

Abstract: A topical therapeutic preparation includes capsaicin which is an extract of peppers or chiles and which is a potent local pain killer. The ointment also includes a norepinephrine inhibitor and preferably a vasodilator which act to promote blood circulation in the treatment area and thereby promote healing of tissues in the treatment area. The ointment also preferably includes a local pain killer to offset the irritating effects of the capsaicin and a promoter of transcutaneous absorption.

Abstract: Compounds, compositions and methods are disclosed for treating mitochondria-associated diseases, such as cancer, psoriasis, stroke, Alzheimer's Disease and diabetes. The compounds of this invention have structure (I) below, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein Ar and L are as defined herein. The methods of this invention are directed to treating a mitochondria-associated disease by administering to a warm-blooded animal in need thereof an effective amount of a compound of structure (I), typically in the form of a pharmaceutical composition.

Abstract: Compounds that provide protection against excitotoxic neuronal damage are selected from the group consisting of Arg-rich oligopeptides and compounds of formula 1: where R1 is alkyl, alkenyl, or hydroxyalkyl, aminoalkyl, or alkoxy-alkyl; and R2 and R3 are each natural or artificial amino acid side chains.

Abstract: Tri- and tetra-substituted guanidines which exhibit a high binding affinity to phencyclidine (PCP) receptors and, more preferably, low affinity to the brain sigma receptors. These guanidine derivatives act as non-competitive inhibitors of glutamate induced responses of the NMDA receptor by acting as blockers for the ion channel of the NMDA receptor-ion channel complex. These compounds thus exert neuroprotective activity and are useful in the therapeutic treatment of neuronal loss in hypoxia, hypoglycemia, brain or spinal cord ischemia, and brain or spinal chord trauma as well as being useful for the treatment of epilepsy, Alzheimer's disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, Huntington's disease, Down's Syndrome, Korsakoff's disease and other neurodegenerative disorders.

Abstract: This invention concerns new methods and compositions that are useful in preventing and ameliorating cachexia, the clinical syndrome of poor nutritional status and bodily wasting associated with cancer and other chronic diseases. More particularly, the invention relates to aromatic guanylhydrazone (more properly termed amidinohydrazone) compositions and their use to inhibit the uptake of arginine by macrophages and/or its conversion to urea. These compositions and methods are also useful in preventing the generation of nitric oxide (NO) by cells, and so to prevent NO-mediated inflammation and other responses in persons in need of same. In another embodiment, the compounds can be used to inhibit arginine uptake in arginine-dependent tumors and infections.

Abstract: The subject of the invention is the products of formula (I): in which R1, R2, R3, R4, R5 and G are as defined in the description, the dotted lines represent an optional second bond, as well as the addition salts with acids and bases and the esters, their preparation process and the intermediates of this process, their use as medicines and the pharmaceutical compositions containing them.

Abstract: Non-peptide GnRH agents capable of inhibiting the effect of gonadotropin-releasing hormone are of the following general formula, where X1, X2, Y, and are defined variables: Such compounds and their pharmaceutically acceptable salts, multimers, prodrugs, and active metabolites are suitable for treating mammalian reproductive disorders and steroid hormone-dependent tumors as well as for regulating fertility, where suppression of gonadotropin release is indicated. Methods for synthesizing the compounds and intermediates useful in their preparation are also described.

Abstract: The present invention relates to a method of treated disordered epithelial tissues such as cold sores and other complications resulting from disorders such as herpes, and the like. The inventive method combines an anti-infective and/or antimicrobial active agent in a carrier, with vigorous agitation of the disordered epithelial tissue for topical treatment thereof under such conditions sufficient to achieve clinically discernable improvement of the disordered epithelial tissue. The preferred anti-infective and/or antimicrobial active agent is an organohalide such as a quaternary ammonium compound, preferably benzalkonium chloride. The inventive method may be used also in connection with a preferred applicator configuration.

Abstract: This invention relates to novel compounds of Formula (1), pharmaceutical compositions and their use in the treatment of disease states mediated by the chemokine, Interleukins-8 (IL-8).

Abstract: An ectoparasite-controlling agent for animals comprising 0.1 to 20% by weight of the neonocotinoid compounds defined in the specification and 10 to 95% by weight of a glycol or glycol monoalkyl ether has an excellent effectiveness by the application methods such as spot-on and pour-on application.

Abstract: The invention relates to a fast drying biocidal composition having enhanced penetration for the treatment and preservation of wood, leather and similar natural products which comprises: A. between about 10 and about 50 wt. % of a concentrate comprising a petroleum distillate boiling above 40° C. and containing (a) between about 0.5 and about 7 wt. % of an active nitrogen- or sulfur-containing biocide and (b) between about 20 and about 55 wt. % of a solvent for said active biocide selected from the group consisting of (i) butyrolactone containing 0 to 85 wt. % N-methyl pyrrolidone and/or 0 to 85 wt. % of a C2 to C4 aliphatic alcohol and (ii) N-methyl pyrrolidone containing 0 to 85 wt. % of a C2 to C4 alcohol and B. from about 90 to about 50 wt. % of a C2to C4 aliphatic alcohol containing 0 to 85 wt. % of mineral spirit as a diluent to provide a sprayable composition and to the process for treating a wood or leather substrate with said biocidal composition.

Abstract: Compositions of cis-jasmone were found to effectively attract adult Lepidoptera. The cis-jasmone may be used alone or in combination with one or more other volatiles of the Japanese honeysuckle flower, particularly linalool and/or phenylacetaldehyde. By attracting the adult Lepidoptera to attracticidal baits and/or field traps, the attractants are useful for the control and monitoring of these agricultural pests.

Abstract: This invention concerns new methods and compositions that are useful in preventing and ameliorating cachexia, the clinical syndrome of poor nutritional status and bodily wasting associated with cancer and other chronic diseases. More particularly, the invention relates to aromatic guanylhydrazone (more properly termed amidinohydrazone) compositions and their use to inhibit the uptake of arginine by macrophages and/or its conversion to urea. These compositions and methods are also useful in preventing the generation of nitric oxide (NO) by cells, and so to prevent NO-mediated inflammation and other responses in persons in need of same. In another embodiment, the compounds can be used to inhibit arginine uptake in arginine-dependent tumors and infections.

Abstract: The present invention provides therapeutically useful substituted guanidines, and methods of treatment and pharmaceutical compositions that utilize or comprise one or more of such guanidines.

Abstract: 15-deoxyspergualin or a pharmaceutically compatible salt thereof is suitable for the preparation of an immunosuppressive, anti-inflammatory or anti-tumoral pharmaceutical, which is effective in a low dosage of 20 to 600 .mu.g/kg body weight when it is applied to the mucous membrane, to which end it is preferably prepared as a dosing aerosol.

Abstract: Fungicidal mixture comprising, as active components,a.sub.1) the oxime ether carboxylate of the formula Ia ##STR1## or a salt or adduct thereof, and/or a.sub.2) a carbamate of the formula Ib ##STR2## where X is CH or N, n is 0, 1 or 2 and R is halogen, C.sub.1 -C.sub.4 -alkyl or C.sub.1 -C.sub.4 -haloalkyl, it being possible for the radicals R to be different if n is 2, or a salt or adduct thereof, andb) iminoctadine IIH.sub.2 N--C(.dbd.NH)--NH--(CH.sub.2).sub.8 --NH--(CH.sub.2).sub.8 --NH--C(.dbd.NH)--NH.sub.2 (II)or a salt or adduct thereof,in a synergistically active amount, and its use for controlling harmful fungi.

Abstract: A method of treating a subject for an unwanted epidermal or dermal condition comprising administering to the subject, a treatment which modulates the level of nitric oxide (NO) in the skin.

Abstract: The present invention provides therapeutically useful substituted guanidines of the following Formula: ##STR1## and methods of treatment and pharmaceutical compositions that utilize or comprise one or more of such guanidines.

Abstract: Non-insulin dependent diabetes mellitus in cases of secondary failure is treated with a combination of glibenclamide and metformin.