Abstract: It is the object of the present invention to provide an industrially useful process for the manufacture of polyguluronic acids having degrees of polymerization less than 20 and substantially free of mannuronic acid contamination. Alginate salts of organic bases are quite soluble in aqueous solution, and remain soluble in aqueous solution throughout a hydrolysis reaction in the range of pH values at which the acidic hydrolysis is effected at a reasonably fast rate. Based on this finding, a solution containing 5 wt. % or more of alginic acid prepared by dissolving alginic acid in water by neutralization with an organic base is provided and then hydrolyzed under acidic conditions, followed by selective precipitation of polyguluronic acids under acidic conditions.

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: Conjugation of 4,5-Epoxymorphinan-6-ols with Bromoglucuronides in the presence of Zinc containing compounds as activator under conditions capable of forming 4,5-Epoxymorphinan-6-oxyglucuronides is disclosed. This novel approach provides an efficient method for preparation of both anomers of 4,5-Epoxymorphinan-6-oxyglucuronides. The deprotected end products are useful as analgesic agents.

Abstract: The present invention relates to arsenic sulfide compounds. The present invention also relates to pharmaceutical compositions useful for treating cancer, such as leukemia or lymphoma, which comprises an arsenic sulfide compound. The present invention further relates to methods for treating cancer, such as leukemia or lymphoma, using an arsenic sulfide compound. Finally, the present invention relates to processes for producing arsenic disulfide (As4S4).

Abstract: Disclosed are derivatized malto-oligosaccharides and methods for the preparation thereof. In accordance with the disclosed invention, a malto-oligosaccharide is hydrogenated to thereby obtain a hydrogenated malto-oligosaccharide, and the resulting hydrogenated malto-oligosaccharide is derivatized, such as via oxidation, esterification, etherification, or enzymatic modification. The derivatization of such hydrogenated malto-oligosaccharides results in a surprisingly low level of a formation of by-products and products of degradation. In a particularly preferred embodiment of the invention, a mixture of malto-oligosaccharides is catalytically hydrogenated under reaction conditions suitable to substantially preserve the degree of polymerization (DP) profile of the mixture. The resulting malto-oligosaccharide mixture then is derivatized to form a derivatized malto-oligosaccharide mixture.

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. Therapeutic uses of Formula I include treatment of sinusitis, otitis media, dry eye, retinal detachment, nasolacrimal duct obstruction, female infertility and irritation due to vaginal dryness, via increased mucus secretions and hydration of the epithelial surface. wherein: X is Na, NH4 or H, provided that all X groups are not H.

Abstract: The invention provides a novel silicon-containing compound having an oxidation potential of 0.3 to 1.5 V on the basis of a standard hydrogen electrode, wherein at least one alkoxy group is bonded to a silicon atom and at least one aromatic amine group is also bonded to the silicon atom. An organic electroluminescence device having excellent mechanical and electric contact between an electrode and an organic layer is also provided by treating the surface of an anode with using a surface-treating agent comprising the above silicon-containing compound.

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: Monomeric and dimeric anti-cancer drug aldehyde conjugate compounds and pharmaceutically acceptable salts thereof. Specifically, monomeric and dimeric aldehyde conjugates of 1-2, dihetero-substituted anti-cancer drugs, including monomeric and dimeric aldehyde conjugates of anthracyclines, are provided. Also provided are pro-drugs which, after administration, release monomeric aldehyde conjugates. Further provided are pharmaceutical and therapeutic compositions containing anti-cancer drug aldehyde conjugates and methods of treating cancer using the aldehyde conjugates.

Abstract: Aryl phosphate derivatives of d4T with para-bromo substitution on the aryl group show markedly increased potency as anti-HIV agents without undesirable levels of cytotoxic activity. In particular, these derivatives are potent inhibitors of HIV reverse transcriptase. In a preferred aspect of the present invention, the phosphorus of the aryl phosphate group is further substituted with an amino acid residue that may be esterified or substituted, such as a methoxy alaninyl group.

Abstract: The present invention relates to a process for effectively preparing L-ribose, which is recognized as being highly important in relation to the development of new antiviral medicines, from 1,4-lactone compound.

Abstract: The invention includes compositions and methods useful for treatment of a virus infection in a mammal by double-targeting the virus (i.e. targeting the virus at more than one stage of the virus life cycle) and thereby inhibiting virus replication. The compositions of the invention include compounds which comprise a phosphocholine moiety covalently conjugated with one or more antiviral agents (e.g. nucleoside analogue, protease inhibitor, etc.) to a lipid backbone. The invention also includes pharmaceutical compositions and kits for use in treatment of a virus infection in mammals. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the invention, in an amount effective to treat the infection, to a mammal infected with a virus. Additionally, the invention includes compositions and methods useful for combating a cancer in a mammal and for facilitating delivery of a therapeutic agent to a mammalian cell.

Abstract: Disclosed are a crystallizing method of doxorubicin hydrochloride from a doxorubicin hydrochloride-containing solution, particularly a method for carrying out the crystallization under a condition of 40° C. or higher, and a doxorubicin hydrochloride crystalline aggregate having particularly an excellent solubility in water.

Abstract: There are disclosed novel Stavudine solvates as follows: Stavudine NN-dimethyllacetamide solvates; Stavudine NN-dimethylacrylamide solvates and Stavudine NN-dimethylpropionamide solvates and processes for producing Stavudine NN-dimethylacetamide solvates, Stavudine NN dimethylacrylamide solvates and Stavudine NN dimethylpropionamide solvates which results in pure Stavudine.

Abstract: Cellulose particles are described that have cationic groups in their interior. In one aspect, at least 10%, and preferably 50% or more, of the cationic groups are present within the particle interior. Also disclosed are particular combinations of such cellulose particles with certain water-soluble polymers that are well suited for use in the papermaking industry.

Abstract: A cytotoxic agent comprising one or more modified doxorubicins/daunorubicin linked to a cell binding agent. A therapeutic composition for killing selected cell populations comprising: (A) a cytotoxic amount of one or more modified doxorubicins/daunorubicins covalently bonded to a cell binding agent through a linking group, and (B) a pharmaceutically acceptable carrier. A method for killing selected cell populations comprising contacting target cells or tissue containing target cells with an effective amount of a cytotoxic agent comprising one or more modified doxorubicins/daunorubicins linked to a cell binding agent. Novel sulfur-containing modified doxorubicins/daunorubicins.

Abstract: Methods for the regioselective alkylation at the 2′-hydroxy position over the 3′-hydroxy position of nucleosides and nucleoside analogs, forming 2′-O-ester modified compounds, are disclosed. Reduction and derivatization of the 2′-O-ester provides 2′-O-modified nucleosides and nucleoside analogs useful for the synthesis of oligomeric compounds having improved hybridization affinity and nuclease resistance.

Abstract: Disclosed are a method for the reduction of an oligosaccharide mixture and an oligosaccharide mixture prepared thereby. In accordance with the disclosed invention, a mixture of oligosaccharides having a given DP profile is reduced to a DE of essentially zero by catalytically hydrogenating the mixture under reaction conditions sufficient to preserve the DP profile of the mixture, which reaction conditions typically include a reaction temperature ranging from about 50° C. to about 150° C. and a reaction pressure ranging up to about 1500 psi. Surprisingly, when the mixture is a malto-oligosaccharide mixture, the reduced mixture will have a superior color-fastness and thermal stability as compared to a similar unreduced mixture of malto-oligosaccharides, and also low reactivity towards nitrogen-containing species.

Abstract: This invention is directed to novel substituted nucleotide bases with a crosslinking arm which accomplish crosslinking between specific sites on adjoining strands of oligonucleotides a oligodeoxynucleotides. The invention is also directed to oligonucleotides comprising at least one of these crosslinking agents and to the use of the resulting novel oligonucleotides for diagnostic and therapeutic purposes.

Abstract: A subject of the invention is the compounds of formula (I): in which R represents a carboxylic acid remainder containing up to 18 carbon atoms the products of formula (I) can be used to prepare antibiotic products.