Abstract: The present invention provides a method of stimulating cervical and vaginal secretions in a mammal by treatment with P2Y2 and/or P2Y4 purinergic receptor agonists. Treatment of vaginal dryness associated with menopause, chemotherapy, and various disease states as well as the treatment of vulvar pain is discussed. Suitable agonists such as UTP, CTP, ATP, dinucleotides and analogs thereof are disclosed.

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: This invention provides a method for treating a patient with neoplasia by an adjuvant therapy that includes treatment with a paclitaxel derivative.

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: The present invention relates generally to a method of producing plant proteins for use in nutritional products that have reduced levels of phytoestrogens, manganese or nucleotides. More specifically, this invention is directed to a method of using ion exchange technology to remove phytoestrogens, manganese or nucleotides from plant proteins. This invention is also directed to the plant protein product resulting from the inventive process and to nutritional products that use the plant protein product as a source of amino nitrogen.

Abstract: The present invention is to provide a multiple-agents-binding compound comprising a compound having anti-HIV activity and having no affinity for cell surface protein bound together with a same or different kind of at least one compound having anti-HIV activity and having no affinity for cell surface protein, or a salt thereof, and a pharmaceutical composition for the prevention or treatment of infectious diseases of HIV or AIDS comprising said multiple-agents-binding compound.

Abstract: A method and preparation for the stimulation of tear secretion in a subject in need of such treatment is disclosed. The method comprises administering to the ocular surfaces of the subject a purinergic receptor agonist such as uridine 5′-triphosphate (UTP), dinucleotides, cytidine 5′-triphosphate (CTP), adenosine 5′-triphosphate (ATP), or their therapeutically useful analogs and derivatives, in an amount effective to stimulate tear fluid secretion and enhance drainage of the lacrimal system. 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: The present invention relates to certain novel dinucleotide polyphosphates of general Formulae I, II and III, and formulations thereof which are selective agonists of the P2Y purinergic receptors. They are useful in the prevention, management or treatment of diseases and disorders associated with abnormalities of tissue fluid secretion, hydration and clearance, including chronic obstructive pulmonary diseases (chronic bronchitis, PCD, cystic fibrosis, immobility-associated pneumonia), sinusitis, otitis media, nasolacrimal duct obstruction, dry eye disease, glaucoma, retinal degeneration, and edematous retinal disorders, including retinal detachment, vaginal dryness, and gastrointestinal tract disease. Finally, these novel dinucleotides may be useful for diagnostic purposes, such as the facilitation of sputum induction and expectoration for the analysis of respiratory tract secretions.

Abstract: A method of stimulating ciliary beat frequency in a subject in need of such treatment is disclosed. The method comprises administering to the airways, ears, eyes, or genito-urinary tract of the subject a triphosphate nucleotide such as uridine 5′-triphosphate (UTP), an analog of UTP, or any other analog, in an amount effective to stimulate ciliary beat frequency. This method is useful for treating patients afflicted with ciliary dyskinesia, Kartagener's syndrome, or any other disease involving dysfunction of ciliary movement, such as male infertility caused by impairment of propulsion of the spermatozoa or immune deficiency caused by impairment of ciliary movement in neutrophils or macrophages. Pharmaceutical formulations and methods of making the same are also disclosed.

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: 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: 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. Oligonucleotides composed of these novel nucleosides are useful for oligonucleotide therapeutic and diagnostic compounds.

Abstract: Compounds of formula RS—P(═O)(QR)—Nu where: R is a radical —(CH2)n—W—X; X is a radical —C(═Z) (Y) or —S—U; Z is O or S; W is O or S; Q is O or S; Y and U are an alkyl, aryl or saccharide radical which is optionally substituted with, for example, an OH, SH or NH group; n is equal to 1 to 4, preferably 1 or 2; and Nu is a radical consisting of a residue of a biologically active compound or the dephosphorylated residue of a compound which is biologically active when it bears a phosphate or phosphonate group.

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: A method and composition for the treatment of HIV and HBV infections in humans and other host animals is disclosed that includes the administration of an effective amount of a [5-carboxamido or 5-fluoro]-2′,3′-dideoxy-2′,3′-didehydro-pyrimidine nucleoside or a [5-carboxamido or 5-fluoro]-3′-modified-pyrimidine nucleoside, or a mixture or a pharmaceutically acceptable derivative thereof, including a 5′ or N4 alkylated or acylated derivative, or a pharmaceutically acceptable salt thereof, in a pharmaceutically acceptable carrier.

Abstract: The present invention relates to a composition for and a method of treating hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, hepatitis D virus (HDV) infection or a proliferative disorder in a patient using an effective amount of a compound selected from the group consisting of formulas [I]- [IV] below and mixtures of two or more thereof: 1

Abstract: This invention is directed to a method of preventing or treating diseases or conditions associated with platelet aggregation. The method is also directed to a method of treating thrombosis. The method comprises administering to a subject a pharmaceutical composition comprising a therapeutic effective amount of P2Y12 receptor antagonist compound, wherein said amount is effective to bind the P2Y12 receptors on platelets and inhibit ADP-induced platelet aggregation. The P2Y12 receptor antagonist compounds useful for this invention include mononucleoside polyphosphates and dinucleoside polyphosphates of general Formula I, or salts thereof. The present invention also provides novel compositions comprising mononucleoside polyphosphates and dinucleoside polyphosphates according to Formula Ia and Ib.

Abstract: A method and preparation for the stimulation of mucosal hydration in a subject in need of such treatment is disclosed. The method comprises administering to the mucosal surfaces of the subject a purinergic receptor agonist such as uridine 5′-diphosphate (UDP), dinucleotide triphosphates; cytidine 5′-diphosphate (CDP), adenosine 5′-diphosphate (ADP), or their therapeutically useful analogs and derivatives, in an amount effective to stimulate mucin secretion. 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: The present invention concerns new phospholipid derivatives of nucleosides of the general formula (I) in which R1 represents a straight-chained or branched, saturated or unsaturated aliphatic residue with 9-14 carbon atoms which can optionally be substituted once or several times; R2 can represent a straight-chained or branched, saturated or unsaturated aliphatic residue with 8-12 carbon atoms which can optionally be substituted once or several times; m is 2 or 3; A can represent a methylene group or an oxygen; Nuc can be a nucleoside or a residue derived from a nucleoside derivative; and tautomers thereof and their physiologically tolerated salts of inorganic and organic acids and bases as well as pharmaceutical preparations containing these compounds.

Abstract: The method, composition, and use of the composition for healing defects in bone or cartilage tissue in animals and humans caused by trauma or surgery is disclosed. The method includes administration of creatine compounds including analogues or pharmaceutically acceptable salts thereof. Treatment in accordance with the method speeds-up time for and improves the process of healing of defects in bone or cartilage tissue in animals and humans caused by trauma or surgery including acceptance and bonding of artificial implants. The treatment with creatine compounds can be therapeutic for diseased patients, preventive for healthy people, as well as geriatric for elderly people.

Abstract: Compounds of formula RS—P(═O) (QR)—Nu where: R is a radical —(CH2)n—W—X; X is a radical —C(═Z) (Y) or —S—U; Z is O or S; W is O or S; Q is O or S; Y and U are an alkyl, aryl or saccharide radical which is optionally substituted with, for example, an OH, SH or NH group; n is equal to 1 to 4, preferably 1 or 2; and Nu is a radical consisting of a residue of a biologically active compound or the dephosphorylated residue of a compound which is biologically active when it bears a phosphate or phosphonate group.

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: The present invention provides protonated compounds having antimicrobial activity. The invention also provides antimicrobial compositions comprising protonated compounds of the invention. The protonated compounds of the invention provide efficacious antimicrobial activity against resistant strains of bacteria and opportunistic fungi.

Abstract: The present invention provides a method of optimizing therapeutic efficacy and reducing toxicity associated with 6-mercaptopurine drug treatment of an immune-mediated gastrointestinal disorder such as inflammatory bowel disease. The method of the invention includes the step of determining the level of one or more 6-mercaptopurine metabolites in the patient having an immune-mediated gastrointestinal disorder.

Abstract: Methods and compositions for enhancing cellular function through protection of a tissue components such receptors, proteins, lipids, nucleic acids, carbohydrates, hormones, vitamins, and cofactors, by administering pyrophosphate analogs or related compounds.

Abstract: The present invention relates to certain novel dinucleotides and formulations thereof which are highly selective agonists of the P2Y2 and/or P2Y4 purinergic receptor. They are useful in the treatment of chronic obstructive pulmonary diseases such as chronic bronchitis, PCD, cystic fibrosis, as well as prevention of pneumonia due to immobility. Furthermore, because of their general ability to clear retained mucus secretions and stimulate ciliary beat frequency, the compounds of the present invention are also useful in the treatment of sinusitis, otitis media and nasolacrimal duct obstruction. They are also useful for treatment of dry eye disease and retinal detachment.

Abstract: The present invention relates to a method for the treatment or prevention of Flavivirus infections using nucleoside analogues in a host comprising administering a therapeutically effective amount of a compound having the formula I or a pharmaceutically acceptable salt thereof.

Abstract: This invention provides a method of killing tumor cells or microorganisms which comprises contacting the tumor cells or the microorganisms with an amount of nicotinamide adenine dinucleotide (NAD) or its analogs effective to increase clonogenic toxicity of cells. This invention also provides a method of killing tumor cells or microoganisms in a subject which comprises administering an amount of nicotinamide adenine dinucleotide or its analogs effective to increase clonogenic toxicity of cells to the subject.

Abstract: The invention provides 4′-C-ethynyl purine nucleosides represented by formula [I]: wherein B represents a base selected from the group consisting of purine and derivatives thereof; X represents a hydrogen atom or a hydroxyl group; and R represents a hydrogen atom or a phosphate residue; and a pharmaceutical composition containing any one of the compounds and a pharmaceutically acceptable carrier. Preferably, the composition is used as an anti-HIV agent or a drug for treating AIDS.

Abstract: Disclosed is a method of treating an HIV-infected host including administering to the host a therapeutic agent that is cytotoxic or cytostatic with respect to CD4+ T cells, but has reduced cytotoxic or cytostatic activity with respect to T lymphocyte stem cells, in a CD4+ T cell cytotoxic or cytostatic effective amount. Also disclosed is a method of treating an HIV-infected host including administering highly active antiretroviral therapy; and coadministering to the host a therapeutic agent that is cytotoxic or cytostatic with respect to CD4+ T cells, but has reduced cytotoxic or cytostatic activity with respect to T lymphocyte stem cells, in a CD4+ T cell cytotoxic or cytostatic effective amount.

Abstract: The present invention provides new methods for the synthesis of the therapeutic dinucleotide, P1,P4-di(uridine 5′-tetraphosphate), and demonstrates applicability to the production of large quantities. The methods of the present invention substantially reduce the time period required to synthesize diuridine tetraphosphate, preferably to three days or less. The novel tetrammonium and tetrasodium salts of P1,P4-di(uridine 5′-tetraphosphate) (Formula I) prepared by these methods are stable, soluble, nontoxic, and easy to handle during manufacture, wherein: X is Na, NH4 or H, provided that all X groups are not H.

Abstract: A sulfated phosphatidylinositol, pharmaceutical compositions containing a sulfated phosphatidylinositol, and the administration of a sulfated phosphatidylinositol or the pharmaceutical compositions to individuals are disclosed. A sulfated phosphatidylinositol can be used alone to elicit a pharmacologic response, or can be incorporated into a variety of pharmaceutical compositions, both liquid and solid, as a component of a drug delivery system for the administration of a therapeutic agent to an individual.

Abstract: Pharmaceutical prodrug compositions are provided comprising azide derivatives of drugs which are capable of being converted to the drug in vivo. Azide derivatives of drugs having amine, ketone and hydroxy substituents are converted in vivo to the corresponding drugs, increasing the half-life of the drugs. In addition azide prodrugs are often better able to penetrate the blood-brain barrier than the corresponding drugs. Especially useful are azide derivatives of cordycepin, 2′-F-ara-ddI, AraA, acyclovir, penciclovir and related drugs. Useful azide prodrugs are azide derivatives of therapeutic alicyclic amines, ketones, and hydroxy-substituted compounds, including aralkyl, heterocyclic aralkyl, and cyclic aliphatic compounds, where the amine or oxygen moiety is on the ring, or where the amine or oxygen moiety is on an aliphatic side chain, as well as therapeutic purines and pyrimidines, nucleoside analogs and phosphorylated nucleoside analogs.

Abstract: Pharmaceutical prodrug compositions are provided comprising azide derivatives of drugs which are capable of being converted to the drug in vivo. Azide derivatives of drugs having amine, ketone and hydroxy substituents are converted in vivo to the corresponding drugs, increasing the half-life of the drugs. In addition azide prodrugs are often better able to penetrate the blood-brain barrier than the corresponding drugs. Especially useful are azide derivatives of cordycepin, 2′-F-ara-ddI, AraA, acyclovir, penciclovir and related drugs. Useful azide prodrugs are azide derivatives of therapeutic alicyclic amines, ketones, and hydroxy-substituted compounds, including aralkyl, heterocyclic aralkyl, and cyclic aliphatic compounds, where the amine or oxygen moiety is on the ring, or where the amine or oxygen moiety is on an aliphatic side chain, as well as therapeutic purines and pyrimidines, nucleoside analogs and phosphorylated nucleoside analogs.

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: An enzyme calibrator sample for measuring enzyme activities, including a solution containing at least three kinds of enzymes having the enzyme activity at least twice the upper limit value reference limit of the reference interval for the enzyme analysis items is produced, and calibration curves for the enzyme analysis items are corrected with the calibrator which can be used as a control sample. Accordingly, apparatus difference of measured values can be reduced when enzyme activity of a testing sample is measured.

Abstract: The specification discloses purine nucleotide analogues which modulate cardiac muscle contractility and possess vasodilator activity. In addition, related methods of administration and the identity of receptors that bind these compounds are disclosed.

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: The invention relates to novel nucleosides and nucleoside dimers containing an L-sugar in at least one of the nucleosides, and their pharmaceutical compositions.

Abstract: A method and composition for the treatment of HIV and HBV infections in humans and other host animals is disclosed that includes the administration of an effective amount of a [5-carboxamido or 5-fluoro]-2′,3′-dideoxy-2′,3′-didehydro-pyrimidine nucleoside or a [5-carboxamido or 5-fluoro]-3′-modified-pyrimidine nucleoside, or a mixture or a pharmaceutically acceptable derivative thereof, including a 5′ or N4 alkylated or acylated derivative, or a pharmaceutically acceptable salt thereof, in a pharmaceutically acceptable carrier.

Abstract: Derivatives of camptothecin are disclosed and are represented by the general formula: wherein when R2 is H, R1 is a C2-C4 alkyl group, a C6-C15 alkyl group, a C3-C8 cycloalkyl group, a C2-C15 alkenyl group or a C2-C15 epoxy group; and when R2 is a nitro group, R1 is a C1-C15 alkyl group, a C2-C5 alkenyl group, a C3-C8 cycloalkyl group, or an epoxy group. Processes for making these derivatives and for using them in cancer treatment are also disclosed.

Abstract: It has been discovered that 3′-azido-2′,3′-dideoxyuridine (CS-87) induces a transient mutation in HIV-1 at the 70th codon (K to R, i.e., lysine to arginine) of the reverse transcriptase region of the virus. Based on this discovery, a method and composition for treating HIV is provided that includes administering CS-87 or its pharmaceutically acceptable salt or prodrug to a human in need of therapy in combination or alternation with a drug that induces a mutation in HIV-1 at a location other than the 70th codon of the reverse transcriptase region. This invention can be practiced by referring to the published mutation patterns for known anti-HIV drugs, or by determining the mutation pattern for a new drug.

Abstract: Novel nucleoside or nucleotide analogs comprising 2'-O-amino residues, processes for their synthesis and incorporation into polynucleotides.

Abstract: The composition and methods of synthesis of phosphorus prodrugs are described. These methods can be used to convert negatively charged phosphorus bearing drugs into neutrally charged; lipid soluble prodrugs which are able to passively diffuse into cells and into tissues in vivo. Prodrugs for a variety of antiviral and anti-leukemic agents are described.

Abstract: Molecular Complexes, comprising of S-(+)-adenosylmethionine and 3'-azido-2',3'-dideoxy nucleosides are prepared, and shown to have synergistic inhibitory effects on the replication of human-immunodeficiency virus 1 & 2 in vitro and in vivo, particularly on the reverse transcriptase, and having a high therapeutic index.

Abstract: A pharmaceutical composition comprising a nucleotide analogue, mannitol and a modifying additive which is sodium chloride or a polyol which is suitable for freeze drying.

Abstract: The present invention provides certain 6-hetarylalkyloxy pyrimidine derivatives of formula II ##STR1## wherein R is (i) a cyclic group having at least one 5- or 6-membered heterocyclic ring, optionally with a carbocyclic or heterocyclic ring fused thereto, the or each heterocyclic ring having at least one hetero atom chosen from O, N, or S, or a substituted derivative thereof; or (ii) phenyl or a substituted derivative thereof,R.sup.2 is selected from H, C.sub.1 -C.sub.5 alkyl, halogen or NH.sub.2,R.sup.4 and R.sup.5 which are the same or different are selected from H, NH.sub.2 or NO.sub.n where n=1 or 2, or R.sup.4 and R.sup.5 together with the pyrimidine ring form a 5- or 6-membered ring structure containing one or more heterocyclic atoms, and pharmaceutically acceptable salts thereof, exhibit the ability to deplete O.sup.6 -alkylguanine-DNA alkyltransferase (ATase) activity.

Abstract: 5',5'-Pyrophosphates of non-naturally occurring nucleosides selected from thymine-3'-azido-2',3'-dideoxy-D-riboside, 5-fluorouracil-2'-deoxy-D-riboside, uracil-3'-azido-2',3'-dideoxy-D-riboside, guanine-2',3'-dideoxy-D-riboside, hypoxanthing-2',3'-dideoxy-D-riboside, cytosine-2',3'-dideoxy-D-riboside, and adenine-2',3'-dideoxy-D-riboside, are described as well as their manufacture and use as therapeutical pharmaceutical compositions or as pro-drugs encapsulated into biological carriers, e.g., transformed erythrocytes, for targeting to specific cell population responsible of the development of the pathological disorders.

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.