Abstract: A compound, method and composition for treating a host infected with a hepatitis C viral comprising administering an effective hepatitis C treatment amount of a described 4′-disubstituted nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

Abstract: The invention relates to novel Acyl coenzyme-A mimics, compositions comprising ketone compounds, and methods useful for treating and preventing cardiovascular diseases, dyslipidemias, dysproteinemias, and glucose metabolism disorders comprising administering a composition comprising a ketone compound. The Acyl coenzyme-A mimics, compositions, and methods of the invention are also useful for treating and preventing Alzheimer's Disease, Syndrome X, peroxisome proliferator activated receptor-related disorders, septicemia, thrombotic disorders, obesity, pancreatitis, hypertension, renal disease, cancer, inflammation, bacterial infection and impotence. In certain embodiments, the Acyl coenzyme-A mimics, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.

Abstract: Disclosed are compositions and methods for alleviating mucositis, wherein said methods and compositions are directed to the formulation or use of selected nucleoside derivatives, especially ADP-ribose, that conform to the general formula A-B-X and pharmaceutically acceptable salts thereof, wherein “A” is a nucleoside structure selected from adenosine, guanosine, and uridine; “B” is a diphosphate linkage attached to the 5′ carbon of the nucleoside ribose moiety; and “X” is attached to B an is a moiety selected from hydrogen, furanose, or pyranose. Also disclosed are pharmaceuticals and nutritional liquid embodiments thereof, including lozenges, mouthwashes, or other product forms that effectively coat the oral, laryngeal or other mucosal areas.

Abstract: D-Ribose and methods for using D-Ribose are provided for enhancing the immune response in mammals. Those with a less than optimal immune response will benefit from oral or parenteral administration of D-Ribose. Methods are also provided for the enhancement of the immune response in isolated leukocytes. Leukocytes are cultured ex vivo in the presence of D-Ribose and transfused into a patient in need of leukocyte augmentation.

Abstract: This invention provides methods and compositions for using nitric oxide in a photoradiation pathogen inactivation process for whole blood and blood components to improve pathogen kill and to improve preservation of the quality of the blood components. This invention provides methods for using nitric oxide in combination with oxygen, photosensitizers, quencher and/or glycolysis inhibitor, and compositions comprising blood components decontaminated by these methods. Nitric oxide is provided using nitric oxide gas, or nitric oxide generators such as L-arginine, and/or N-acetyl-cysteine. This invention also provides compositions suitable for photoradiation pathogen inactivation that include fluid comprising a blood component, a photosensitizer, and dissolved nitric oxide. This invention provides decontamination systems useful for performing the methods of this invention and methods for making the decontamination systems.

Abstract: The present invention comprises nucleoside derivatives for use in the treatment or prophylaxis of hepatitis C virus infections. In particular, the present invention discloses the novel use of known 2′-deoxy-2′-fluoro nucleoside derivatives as inhibitors of hepatitis C virus (HCV) RNA replication and pharmaceutical compositions of such compounds. The compounds of this invention have potential use as therapeutic agents for the treatment of HCV infections.

Abstract: The invention provides compounds comprising at least one phosphohalohydrin group of the formula: where X is a halogen selected from among I, Br, Cl, R1 is selected from among —CH3 and —CH2—CH3, Cat+ is an organic or inorganic cation, and n is an integer between 2 and 20, processes for the production thereof and uses thereof, in particular therapeutic uses and for activating primate T&ggr;9&dgr;2 lymphocytes.

Abstract: The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The pharmaceutical formulation useful in this invention comprises a P2Y receptor agonist with enhanced resistance to extracellular hydrolysis, such as dinucleoside polyphosphate compounds, or hydrolysis-resistant mononucleoside triphosphates.

Abstract: Based on research for compounds that can display a corneal epithelial migration promoting effect in ophthalmology, the present invention provides P2Y receptor agonist corneal epithelial migration promoters, such as phosphoric acid compounds having an adenosyl group, uridyl group, xanthosyl group, guanosyl group, or thymidyl group, or their salts, with excellent corneal epithelial migration promoting effects.

Abstract: Methods are provided for treating heart failure, increasing cardiac muscle contractility, increasing cardiac diastolic relaxation, and increasing vasodilation employing AMP, ADP, and ATP analogues.

Abstract: An ophthalmic solutions that are broad ranged and effective in low concentrations relative to state of the art systems. In particular it has been found that ophthalmic solutions comprising 0.00001 to about 1.0 percent by weight of a nucleotide, a nucleoside or a purine or pyrimidine base; 0.00001 to about 0.05 percent by weight a cationic, polymeric preservative display an effective preservative capacity, and an increased capacity over state-of-the-art preservative systems.

Abstract: This invention relates to a quick-release tablet formulation with >99.19% pure fludara (high-purity fludara) as an active ingredient in a defined composition of residual contaminants.

Abstract: The invention provides new methods for synthesis of nucleotide-based compounds and new libraries of such compounds. Compounds of the invention are useful for a variety of therapeutic applications, including treatment of viral or bacterial infections and associated diseases and disorders.

Abstract: This invention relates to nucleotide-based prodrugs and their drug-delivery applications. The nucleotide-based prodrugs of the present invention comprise a drug component covalently attached via junctional ester bond(s) to one or more nucleotide components. Release and activation of the drug component of a nucleotide-based prodrug arises from hydrolysis of the junctional ester bond joining the nucleotide component to the drug component. The active drug component may be a nucleoside analog, a nucleic acid ligand, or a non-nucleoside drug. The nucleotide component provides a means of targeting and/or anchoring the nucleotide-based prodrug to the desired tissue compartment and/or a mechanism of sustained release of the active drug, thereby providing for a more effective drug delivery system with reduced toxicity.

Abstract: The present invention is directed to a method of treating pain. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a P2X receptor antagonist. The methods of the present invention are useful in reducing pain, such as traumatic pain, neuropathic pain, organ pain and pain associated with diseases. The P2X receptor antagonists particularly useful for this invention are mononucleoside polyphosphate derivatives or dinucleoside polyphosphate derivatives of general Formula I. The compounds of the present method can be used alone to treat pain. The compounds of the present method can also be used in conjunction with other therapeutic agents or adjunctive therapies commonly used to treat pain, thus enhancing the overall pain-reducing effect in a subject in need of such treatment.

Abstract: A therapeutically active composition of thioretinaco ozonide is provided for providing anticarcinogenic, antineoplastic, antiviral, antiatherogenic, and antiaging benefits having the formula:

Abstract: There is provided a composition including an ATP-inducing compound or ATP and an effective amount of cell death-inducing drug. Also provided is the method of inducing apoptosis in apoptosis-inducible cells by administering to the apoptosis inducible cells a composition including an effective amount of a cell death-inducing compound and an ATP-inducing compound or ATP. The present invention also provides a method of suppressing necrosis in cells by administering an effective amount of an ATP-inducing compound or ATP to a cell population, thereby inhibiting necrosis.

Abstract: Compounds are disclosed for treating AIDS, herpes, and other viral infections by means of lipid derivatives of antiviral agents. The compounds consist of nucleoside analogues having antiviral activity which are linked, commonly through a phosphate group at the 5′ position of the pentose residue, to one of a selected group of lipids. The lipophilic nature of these compounds provide advantages over the use of the nucleoside analogue alone. It also makes it possible to incorporate them into the lamellar structure of liposomes, either alone or combined with similar molecules. In the form of liposomes, these antiviral agents are preferentially taken up by macrophages and monocytes, cells which have been found to harbor the target HIV virus. Additional site specificity may be incorporated into the liposomes with the addition of ligands, such as monoclonal antibodies or other peptides or proteins which bind to viral proteins.

Abstract: A method and composition for treating a host infected with hepatitis D comprising administering an effective hepatitis D treatment amount of a described 2′-deoxy-&bgr;-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof.

Abstract: It was found that normal human stem cells produce a regulated non-processive telomerase activity, while cancer cells produce a processive telomerase activity. Nucleotide analogs, such as 7-deaza-2′-deoxyquanosine-5′-triphosphate (7-deaza-dGTP) were found to be substrates for processive telomerase and incorporated into telomeric sequence. The incorporation of this nucleotide subsequently affected the processivity of telomerase, converting processive telomerase to non-processive telomerase. The incorporation of this nucleotide analogs was also found to inhibit formation of G-quartets by telomeric sequence. Other methods for converting cancer processive telomerase to the more benign non-processive telomerase include partially cleaving the telomerase RNA.

Abstract: The present invention provides a method of preventing or treating an inflammatory disease, including but not limited to, sinusitis, rhinitis, conjunctivitis, asthma, dermatitis, inflammatory bowel disease, inflammatory collagen vascular diseases, glomerulonephritis, inflammatory skin diseases, and sarcoidosis. The method comprises administrating to a subject a pharmaceutical formulation comprising a nucleotide receptor agonist, such as nucleoside diphosphate, nucleoside triphosphate, or dinucleoside polyphosphate, according to general formula Ia, Ib, IIa, IIb, or III. Preferred indications of the present invention are perennial allergic rhinitis, seasonal allergic rhinitis, infectious allergic rhinitis, and allergic conjunctivitis.

Abstract: Thiolester-activated amino acids; thiolester-activated nucleotides; polypeptide-oligonucleotide fusions comprising a polypeptide of interest and a thiolester-activated nucleotide; methods of producing the thiolester-activated nucleotides of the present invention; methods of producing polypeptide-oligonucleotide fusions of the present invention; and methods in which the polypeptide-oligonucleotide fusions are used, such as methods of delivering nucleic acid molecules into cells and cell lines.

Abstract: This invention provides a method for treating a patient with neoplasia by an adjuvant therapy that includes treatment with an antineoplastic platinum coordination complex.

Abstract: The invention relates to new compositions and medical uses, such as anti-infectious pharmacology. The compositions include salts and compounds of GSSG including at least one counterion comprising a nitrogenous base. Examples of such nitrogenous bases include DNA bases, nucleosides of DNA bases, nucleotides of DNA bases, RNA bases, nucleosides of RNA bases, nucleotides of RNA bases, inosine, nucleotides of inosine, and homologues, analogues and derivatives thereof. The invention is also directed to methods for treatment and prevention of infectious diseases such as viral hepatitis B and C, AIDS and herpes.

Abstract: Provided are methods and compositions for treating hepatitis virus infections in mammals, especially humans. The methods comprise (1) administering N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds in combination with nucleoside antiviral agents, nucleotide antiviral agents, mixtures thereof, or immunomodulating/immunostimulating agents, or (2) administering N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds in combination with nucleoside antiviral agents, nucleotide antiviral agents, or mixtures thereof, and immunomodulating/immunostimulating agents.

Abstract: This invention is directed to a method for treating a host infected with hepatitis B comprising administering an effective amount of an anti-HBV biologically active 2′-deoxy-&bgr;-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof, wherein the 2′-deoxy-&bgr;-L-erythro-pentofuranonucleoside has the formula: wherein R is selected from the group consisting of H, straight chained, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, mono, di, or triphosphate, or a phosphate derivative; and BASE is a purine or pyrimidine base which may be optionally substituted.

Abstract: This invention is directed to a method for treating a host infected with hepatitis B comprising administering an effective amount of an anti-HBV biologically active 2′-deoxy-&bgr;-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof, wherein the 2′-deoxy-&bgr;-L-erythro-pentoftiranonucleoside has the formula: wherein R is selected from the group consisting of H, straight chained, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, mono, di, or triphosphate, or a phosphate derivative; and BASE is a purine or pyrimidine base which may be optionally substituted.

Abstract: The present invention relates generally to the fields of immunopreventive therapy and vaccine development. More particularly, it concerns compositions and methods of use of the bacterial nucleotides ppGpp and pppGpp and their analogs as adjuvants that can be used to generate more potent and robust vaccines in a shorter period of time, was well as antibodies produced using the disclosed compositions and methods. The inventor has found novel immunomodulatory activities for this group of nucleotides.

Abstract: The present invention comprises nucleoside derivatives for use in the treatment or prophylaxis of hepatitis C virus infections. In particular, the present invention discloses the novel use of known 2′-deoxy-2′-fluoro nucleoside derivatives as inhibitors of hepatitis C virus (HCV) RNA replication and pharmaceutical compositions of such compounds. The compounds of this invention have potential use as therapeutic agents for the treatment of HCV infections.

Abstract: A method and composition for treating a host infected with flavivirus or pestivirus comprising administering an effective flavivirus or pestivirus treatment amount of a described 1′, 2′ or 3′-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

Abstract: A method and composition for treating a host infected with hepatitis C comprising administering an effective hepatitis C treatment amount of a described 1′, 2′ or 3′-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

Abstract: Non-naturally-occurring compositions for use in amelioration of disruption of energy metabolism secondary to stress are described. These compositions comprise a flavonoid or derivative thereof and a synergist. Synergists include, but are not limited to, amino acids, carbohydrates, carnitines, flavonoids, nucleosides, and tocopherols and/or derivatives thereof. Methods of making these compositions and methods of ameliorating disruption of energy metabolism secondary to stress, comprising administering such synergistic compositions, are also disclosed.

Abstract: Inosine compounds, compositions comprising an inosine compound and methods for treating or preventing an inflammation disease or a reperfusion disease comprising administering an effective amount of an inosine compound to a patient in need thereof are disclosed.

Abstract: The present invention is directed to a method of stimulating ciliary beat frequency to promote mucociliary or cough clearance of retained mucus secretions from the lungs, sinuses, upper airways, ears, eyes, genito-urinary tract, spermatozoa, ovaries, fallopian tubes, neutrophils, and macrophages of a patient. The method comprises administering uridine triphosphates, adenosine triphosphates, cytidine triphosphates, or dinucleoside tetraphosphates and the derivatives thereof to an affected body of a patient, to treat dysfunction of the mucociliary clearance system as a result of impaired ciliary movement in the patient.

Abstract: The present invention provides novel pharmaceutical combinations and their use in anti-thrombotic therapy.

Abstract: Conformationally restricted 2′, 4′-bridged nucleoside analogues are described herein. The compounds can be prepared by cyclization at C2′ and C4′ of nucleosides through a linker or linking molecule. These novel nucleosides have a desired, locked sugar pucker and are potentially useful as pharmaceutical ingredients, and especially for use in treatment of HCV.

Abstract: The invention provides methods and compositions for promoting neural cell growth and/or regeneration. The general methods involve contacting with an activator of a cyclic nucleotide dependent protein kinase a neural cell subject to growth repulsion mediated by a neural cell growth repulsion factor. The activator may comprise a direct or an indirect activator of the protein kinase; the repulsion factor typically comprises one or more natural, endogenous proteins mediating localized repulsion or inhibition of neural cell growth; and the target cells are generally vertebrate neurons, typically injured mammalian neurons. The subject compositions include mixtures comprising a neural cell, an activator of a cyclic nucleotide dependent protein kinase and a neural cell growth repulsion factor.

Abstract: The present invention provides methods and compositions for slowing the transit time of pharmaceutical compounds, nutritional supplements, and vitamins through the gastrointestinal tract, prolonging residence time of such compounds, and thereby increasing absorption in the small intestine, by utilizing the cellular regulatory compound cyclic GMP. The present invention also provides methods and compositions for enhancing the bioavailability and therapeutic effectiveness of pharmacologically active agents, vitamins, and nutritional supplements.

Abstract: A method for treating a human being having or suspected of having sexual dysfunction or a disorder of physiological and/or anatomical response to sexual stimulation, said dysfunction or disorder involving erectile tissue of genitalia comprising administering the nitrogen monoxide donor arginine and at least on nucleotide selected from the group consisting of AMP or ATP.

Abstract: Methods for inhibiting angiogensis are disclosed the comprise administering oleouropein and/or the products of its hydrolysis in therapeutically effective amounts. The methods and compositions of the present invention are particularly effective in inhibiting the vascularization of endothelial cells, and may be utilized to treat a wide variety of cancers, ocular diseases, and inflammatory conditions.

Abstract: A class of 2′-fluoro-nucleoside compounds are disclosed which are useful in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cellular proliferation, including tumors and cancer.

Abstract: This invention is directed to a method of stimulating tear secretion and mucin production in eyes. The method comprises the step of administering to the eyes of a subject a composition comprising a compound of Formula I, II, III, or IV and its pharmaceutically acceptable salts, in an amount effective to stimulate tear fluid secretion. The method of the present invention may be used to increase tear production for any reason, including, but not limited to, treatment of dry eye disease and corneal injury. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include: topical administration via a liquid, gel, cream, or as part of a contact lens or selective release membrane; or systemic administration via nasal drops or spray, inhalation by nebulizer or other device, oral form (liquid or pill), injectable, intra-operative instillation or suppository form.

Abstract: A series of 2-(Purin-9-yl)-tetrahydrofuran-3,4-diol derivatives with broad anti-inflammatory properties which inhibit leukocyte recruitment and activation and which are agonists of the adenosine 2a receptor are described.

Abstract: Nucleotides that block the bitter taste of foods, beverages, pharmaceutically active oral dose preparations, cosmetics and other bitter compounds that come into contact with taste tissue. The nucleotides consist of a purine or pyrimidine group, or derivative thereof, and an ionizable phosphate or other anionic organic molecule.

Abstract: Novel purine L-nucleoside compounds are disclosed, in which both the purine rings and the sugar are either modified, functionalized or both. The novel compounds or pharmaceutically acceptable esters or salts thereof may be used in pharmaceutical compositions, and such compositions may be used to treat an infection, an infestation, a neoplasm, or an autoimmune disease. The novel compounds may also be used to modulate aspects of the immune system, including modulation of Th1 and Th2.

Abstract: The invention provides nucleosides of formulae (I), (II), (V) and (VII) as described in the specification which possess antiviral and anticancer activity. Treatment of breast cancer is a preferred embodiment.

Abstract: A method of improving DNA repair and reducing DNA damage and for reducing mutation frequency in skin for the purpose of reducing consequences of exposure to solar or ultraviolet radiation is disclosed. The methods comprise administering to the skin a composition containing deoxyribonucleosides in concentrations sufficient to enhance DNA repair or reduce mutation frequency in a vehicle capable of delivering effective amounts of deoxyribonucleosides to the necessary skin cells.

Abstract: Human mast cell activation is modulated by ATP binding to P2-purinoceptors on the mast cell surface. ATP binding to the purinoceptors provides a target for therapeutic intervention for the treatment of disorders characterized by undesireable mast cell mediator release, such as asthma and allergy. Inhibitors of ATP binding to mast cell P2-purinoceptors are useful therapeutic agents for treatments of those disorders. Methods of treatment using agents, and in vitro screening assays for selection of the therapeutic agents, are described.

Abstract: A material or mixture of materials which is not itself storage stable is rendered storage stable by incorporation into a water-soluble or swellable glassy or rubbery composition which can then be stored at ambient temperature. Recovery is by adding aqueous solution to the composition.

Abstract: The invention relates to a 3′-substituted nucleoside derivative represented by the following general formula (1): wherein B means a nucleic acid base which may have a substituent, Z represents a lower alkynyl or lower alkenyl group which may be substituted by a group represented by the formula: in which Ra, Rb and Rc are individually a lower alkyl group or a phenyl group, or an oxiranyl group which may have at least one lower alkyl group, R1 and R2 individually represent H or an ester-forming residue capable of easily leaving in a living body, and R3 is H, a mono- or polyphosphoric acid residue, or an ester-forming residue capable of easily leaving in a living body, with the proviso that the sugar moiety is ribose, or a pharmaceutically acceptable salt thereof. The 3′-substituted nucleoside derivative according to the invention has an excellent antitumor activity and is hence useful for treatment for and prevention of cancers.