The Brigham and Women's Hospital, Inc.

Ceramoptec Industries, Inc.

Biolitec Pharma Marketing Ltd

Inje University Industry-Academic Cooperation Foundation

Nikolay Nifantiev

Gerald B Pier

Yury Tsvetkov

Marina Gening

Dmitri V Yashunsky

Volker Albrecht

Wolfgang Neuberger

Jin Woo Han

Arno Wiehe

Burkhard Gitter

Susanna Gräfe

Dietrich Scheglmann

Gerhard Wieland

Alfred Fahr

Hyoung Kyu Kim

Albrecht Volker

Dmitry Vladimirovich Yashunsky

Nari Kim

Larisa K Shubina

Tatyana N Makarieva

Mihaela Gadjeva

Seung Hun Jeong

Valentin A Stonik

Igor V Zavarzin

In-Sung Song

The present application provides a compound of Formula (I): [Formula I] or a pharmaceutically acceptable salt thereof, wherein R, R, R, R, R, R, W, L, R, and Rare as described herein. Pharmaceutical compositions including these compounds and methods of using these compounds for treating parasitic infections (e.g., malaria), cancer, cardiovascular diseases, neurological diseases, inflammatory diseases, neuropathic pain, and other conditions are also disclosed herein.

Inhibitors of macrophage migration inhibitory factor

The invention relates to the compositions of synthetic oligo-&#x3b2;-(1&#x2192;6)-2-amino-2-deoxy-D-glu-copyranosides conjugated to carriers, and methods for making and use same.

Methods and compositions relating to synthetic beta-1,6 glucosamine oligosaccharides

The present invention relates to novel pyridine nucleoside compounds, Neopetroside A (NPS A) and Neopetroside B (NPS B) obtained by fractionating an extract ofsp. which is a marine sponge, with ethanol, into n-butanol (n-BuOH). When the NPS A was treated with myocardial cells, it activates oxidative phosphorylation, basal and mitochondrial respiration induced by ATP and ATP synthesis, and stimulates the glycolysis activity and when the NPS A was treated with an ischemic reperfusion injury model, the left ventricular pressure injured by ischemic reperfusion was recovered and the size of myocardial injury site was significantly reduced and as a result, can be provided as the pharmaceutical composition for preventing or treating ischemic heart disease or the health functional food for preventing or improving the same.

Neopetrosides A and B, and synthesis method thereof

The invention relates to the compositions of synthetic oligo-&#x3b2;-(1&#x2192;6)-2-amino-2-deoxy-D-glucopyranosides conjugated to carriers, and methods for making and use same.

Antimicrobial molecular conjugates for the treatment and prevention of infectious diseases caused by pathogenic microorganisms in human and animals are provided. The key to these conjugates is a special spacer connecting at least one photosensitizer to a microorganism receptor (vector) which in turn binds selectively to the surface of a microorganism bringing about photo-destruction upon irradiation. Spacers having hydrophilic structure such as ethylene glycol units and amino carboxyl end capped ethylene glycol units must be used for linking the vector to the photosensitizer. In a preferred embodiment a spacer would have at least 3 ethylene glycol units and be end capped with a carboxyl group on one end and a amino group at the other end. The present invention effectively works to combat bacterial infection in the real patient-related environments where blood, serum and other body fluids are always present or at least nearby. Spacers of selected length and structure, in preferred embodiments, are used for linking the vector to the photosensitizer. These conjugate are found to be very effective in combating bacterial infection in the real patient-related environments where blood, serum and other body fluids are always present or a least nearby. A method of use is also provided.

Anti-microbial photodynamic therapy

Oral formulations and method of formulating photosensitive agents for oral administration during photodynamic therapy (PDT) and Antimicrobial photodynamic therapy (APDT) treatment are presented. The oral formulated photosensitizers show increased solubility and permeability, thus improving the bioavailability of photosensitizers at the treatment site. An orally administered photosensitizer is suitably formulated for mucosal adhesion and absorption via gastrointestinal mucosal membranes. Oral formulation provided herein use lipids and known proteins as carriers for photosensitizers by oral route. Carriers for encapsulating preselected photosensitizers include conventional liposomes, pegylated liposomes, nanoemulsions, nanocrystrals, nanoparticles, fatty emulsions, lipidic formulations, hydrosols, SMEDDS, Alpha-Feto protein (AFP), and Bovine-Serum-Albumin (BSA), fatty emulsions, hot-melt-extrudates and nanoparticles. The oral formulation, in case of a hydrophobic photosensitizer in the present invention, is stabilized using suitable surfactants/solubilizers thus preventing aggregation of the drug in the stomach and until it is absorbed in the duodenum and the small intestine. Oral formulations can be administered in the form of liquid, capsule, tablet, powder, paste or gel. Formulated drugs can be administered orally as one single dose or in multiple doses before administering PDT. In one embodiment Temoporfin (m-THPC) is used as a photosensitizer in the oral formulations. Temoporfin like many hydrophobic photosensitizers are especially suitable to be administered orally because there is no known enzyme system in the mammalian body which can metabolize Temoporfin or similar photosensitizers. Temoporfin can reach the blood system unchanged and fully active after absorption of the formulation in the gastrointestinal tract.

Oral formulations for tetrapyrrole derivatives

A new treatment regime is presenter using a low concentration formulation at a low dosage of hydrophobic photosensitizers (PS) that shows improved pharmacokinetics and an effective method for photodynamic therapy ('PDT'). The new formulation has better pharmacological effect compared to standard photosensitizer formulation with standard dosage. It was found that PDT treatments using the disclosed low concentration formulations provide for more accurate, more efficient and more convenient dosing. It was found that the inventive formulation; (1) reduces the time for a therapeutically effective level of photosensitizer to accumulate in diseased tissue; and, (2) reduces the time for achieving a sufficient ratio of photosensitizer in diseased tissue vs. healthy tissue. As a result, the formulation of the invention reduces the time interval between PS application/administration and irradiation (the drug-light interval or 'DLI') and can provide for a &#x201c;same day&#x201d; PDT treatment option. The inventive formulation can be used for PDT treatment regimes where photosensitizers are administered in at least one preselected dose, including a low concentration therapy for PDT. In particular, when meta-(Tetrahydroxyphenyl)Chlorin (m-THPC) is the photosensitizer, then a concentration of 0.8 mg/ml to 0.04 mg/ml in a mixture of pure propylene glycol and ethanol in a 3:2 volume ratio accumulates in diseased tissue and differentiates between diseased tissue and normal tissue sufficiently quickly for 'one day' or overnight administration and activation treatment procedures to be possible.

Photosensitizer formulations and their use

Methods and compositions relating to synthetic &#x3b2;-1,6 glucosamine oligosaccharides

A low concentration formulation for hydrophobic photosensitizers (PS) and method for photodynamic therapy ('PDT') using the disclosed low concentration formulations provide for more accurate, more efficient and more convenient dosing. The inventive formulation (1) reduces the time for a therapeutically effective level of photosensitizer to accumulate in diseased tissue and (2) reduces the time for achieving a sufficient ratio of photosensitizer in diseased tissue vs. healthy tissue. The inventive formulation reduces the time interval between PS application/administration and irradiation (the drug-light interval or 'DLI') and can provide for a &#x201c;same day&#x201d; PDT treatment option. 0.08 mg/ml to 1.3 mg/ml meta Tetra-Hydroxy-Phenyl Chlorin (m-THPC) as the photosensitizer in a mixture of pure propylene glycol and ethanol (3:2 volume ratio) accumulates in diseased tissue and differentiates between diseased tissue and normal tissue sufficiently quickly for 'one day' or overnight administration and activation treatment procedures to be possible.

Water-soluble mono-PEGylated tetrapyrrole derivatives are disclosed, having a formula given by formula 1, 2, or 3 in the specification. A method to produce the above water-soluble mono-PEGylated compounds is also disclosed, comprising an interaction of a tetrapyrrole with an aminopolyethylene glycol containing a functionalized terminal fragment, as well as their use as photosensitizers in photodynamic therapy.

Water-soluble mono-PEGylated tetrapyrrole derivatives for photodynamic therapy and method of production

High purity pharmaceutical-grade water-soluble porphyrin derivatives given by formula 1 or 2 in the specification, and new methods to prepare and use such porphyrin derivatives are disclosed. A preferred method comprises the steps of one- or two-step direct acidic alcoholysis of biological raw material producing a crystalline alkyl pheophorbide, conversion of the obtained alkyl pheophorbide into an acidic porphyrin, and reaction of the acidic porphyrin in water or in an aqueous organic solution with a hydrophilic organic amine. Another preferred method comprises reaction of acidic porphyrins prepared in water or in aqueous organic solution with a hydrophilic organic amine. Another preferred method comprises the additional step of purification of the resultant water-soluble porphyrin derivative by reversed phase chromatography using volatile solvents. The disclosed compounds are useful as photosensitizers for the photodynamic therapy of cancer, infectious and other diseases as well as for light irradiation treatments in other cases.

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Moscow, Russia

Nikolay Nifantiev