ПРИМЕНЕНИЕ ПРОИЗВОДНЫХ 3,5-ВТОР-4-НОРХОЛЕСТАНА ДЛЯ ПОЛУЧЕНИЯ ЛЕКАРСТВЕННОГО СРЕДСТВА - ЦИТОПРОТЕКТОРА

Настоящее изобретение относится к области фармакологии и медицины и касается применения производных 3,5-втор-4-норхолестана для получения лекарственного средства-цитопротектора, обладающего высокой активностью, за исключением нейропротектора. 3 н. и 16 з.п. ф-лы, 2 табл.

СПОСОБ ЛЕЧЕНИЯ СОСТОЯНИЙ, СВЯЗАННЫХ С ФАКТОРОМ, ИНДУЦИРУЕМЫМ ГИПОКСИЕЙ (HIF)

Заявленное изобретение относится к области медицины и фармакологии и представляет собой способ лечения инсульта головного мозга, вызванного окклюзией средней мозговой артерии, включающий: введение пациенту композиции, содержащей трансферрин, при этом трансферрин является смесью апотрансферрина и голотрансферрина в соотношении 98% апотрансферрина : 2% голотрансферрина, и при этом апотрансферрин вводится в количестве 385 мг/кг. Использование заявленного изобретения эффективно для лечения инсульта головного мозга, вызванного окклюзией средней мозговой артерии. 4 з.п. ф-лы, 14 ил., 1 табл., 13 пр.

КОМПОЗИЦИИ ДЛЯ ЛЕЧЕНИЯ ЗЛОУПОТРЕБЛЕНИЯ ВЕЩЕСТВАМИ, ВЫЗЫВАЮЩИМИ БОЛЕЗНЕННОЕ ПРИСТРАСТИЕ, И УЛУЧШЕНИЯ ПОВЕДЕНИЯ, СВЯЗАННОГО СО ЗЛОУПОТРЕБЛЕНИЯМИ

Группа изобретений относится к медицине, конкретно к композиции, применению композиции и способу лечения злоупотребления веществами, вызывающими болезненное пристрастие, у субъекта. Композиция содержит карбамоильное соединение, или его фармацевтически приемлемую соль, или сложный эфир в качестве активного ингредиента, и способ включает введение терапевтически эффективного количества карбамоильного соединения, или его фармацевтически приемлемой соли, или сложного эфира. Композиция используется для лечения злоупотребления веществами, вызывающими болезненное пристрастие, у субъекта, а также улучшения поведения, связанного со злоупотреблением. 2 н. и 12 з.п. ф-лы, 1 табл., 3 пр.

ЛИПИДНЫЕ КОМПОЗИЦИИ РАЦЕКАДОТРИЛА

Изобретение относится к фармацевтической микроэмульсионной композиции для лечения диареи. Композиция включает рацекадотрил, полиоксил 35 касторовое масло в качестве поверхностно-активного вещества, триглицериды каприловой/каприновой кислот 70 : 30 в качестве липида и воду. Также описаны дозированная форма для лечения диареи, содержащая указанную фармацевтическую микроэмульсионную композицию, и способ лечения субъекта, страдающего диареей, включающий пероральное введение указанной композиции. Жидкая фармацевтическая микроэмульсионная композиция рацекадотрила по изобретению является стабильной в течение 3 месяцев при 40°С. 3 н. и 3 з.п. ф-лы, 5 табл., 2 пр.

НОВАЯ УЛУЧШЕННАЯ КОМПОЗИЦИЯ РАЦЕКАДОТРИЛА

Данное изобретение относится к композиции рацекадотрила с немедленным и пролонгированным высвобождением, единичной дозе или двухкамерной упаковке, содержащей данную композицию, а также к применению и способу лечения субъекта, страдающего от заболевания или расстройства в желудочно-кишечном тракте. 4 н. и 11 з.п. ф-лы, 4 пр., 3 ил.

КОМПОЗИЦИИ И СПОСОБЫ ЛЕЧЕНИЯ ИЛИ ПРЕДУПРЕЖДЕНИЯ ВОСПАЛИТЕЛЬНЫХ ЗАБОЛЕВАНИЙ

... 1. Способ лечения или предупреждения рассеянного склероза, включающий введение пациенту терапевтически эффективного количества антимикротрубочкового агента таким образом, что рассеянный склероз лечится или предупреждается. 2. Способ по п.1, в котором вышеуказанный антимикротрубочковый агент выбран из группы, состоящей из эпотилона А или В, дискодермолида, оксида дейтерия (D2 O), гексиленгликоля, туберцидина, LY290181, фторида алюминия, бис(сукцинимидилсукцината)этиленгликоля, этилового эфира глицина, а также их аналогов или производных. 3. Способ по п.1, в котором вышеуказанный антимикротрубочковый агент является паклитакселом или его аналогом или производным. 4. Способ лечения или предупреждения псориаза, включающий введение пациенту терапевтически эффективного количества антимикротрубочкового агента таким образом, что псориаз лечится или предупреждается. 5. Способ по п.4, в котором вышеуказанный антимикротрубочковый агент выбран из группы, состоящей из эпотилона А или В, дискодермолида ...

ЛИОФИЛИЗИРОВАННЫЕ ПРЕПАРАТЫ МЕЛФАЛАНА ФЛУФЕНАМИДА

... 1. Лиофилизированный фармацевтический препарат, содержащий гидрохлорид мелфалана флуфенамида (J1) или его фармацевтически приемлемую соль и сахарозу, в котором массовое соотношение указанного гидрохлорида мелфалана флуфенамида (J1) и сахарозы составляет от приблизительно 1:25 до приблизительно 1:75.2. Лиофилизированный фармацевтический препарат по п. 1, в котором массовое соотношение указанного гидрохлорида мелфалана флуфенамида (J1) и сахарозы составляет приблизительно 1:50.3. Лиофилизированный фармацевтический препарат по п. 1 или 2, содержащий приблизительно 25 мг гидрохлорида мелфалана флуфенамида (J1) и приблизительно 1,25 г сахарозы.4. Лиофилизированный фармацевтический препарат по п. 1 или 2, содержащий приблизительно 50 мг гидрохлорида мелфалана флуфенамида (J1) и приблизительно 2,5 г сахарозы.5. Лиофилизированный фармацевтический препарат по п. 1 или 2, содержащий приблизительно 15 мг гидрохлорида мелфалана флуфенамида (J1) и приблизительно 0,75 г сахарозы.6. Лиофилизированный ...

СИНЕРГЕТИЧЕСКИЕ АНТИБАКТЕРИАЛЬНЫЕ ЭФФЕКТЫ ЭКСТРАКТА КОРЫ МАГНОЛИИ И СЛОЖНОГО ЭТИЛОВОГО ЭФИРА Nα-ЛАУРОИЛ-АРГИНИНА НА БИОПЛЕНКУ ЗУБНОГО НАЛЕТА

ЖИДКИЕ КОМПОЗИЦИИ РАЦЕКАДОТРИЛА

ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СОДЕРЖАЩАЯ РАЦЕКАДОТРИЛ, И СПОСОБ ЕЕ ПОЛУЧЕНИЯ

ИЗОПРОПИЛОВЫЙ ЭФИР [((1R, 2S, 5R)-2-ИЗОПРОПИЛ-5-МЕТИЛЦИКЛОГЕКСАНКАРБОНИЛ)-АМИНО]-УКСУСНОЙ КИСЛОТЫ, РОДСТВЕННЫЕ СОЕДИНЕНИЯ И ИХ ПРИМЕНЕНИЕ В ТЕРАПИИ

... 1. Соединение, представляющее собой:изопропиловый эфир [((1R,2S,5R)-2-изопропил-5-метилциклогексанкарбонил)-амино]-уксусной кислоты, илиизопропиловый эфир [((1R,2S,5R)-2-изопропил-5-метилциклогексанкарбонил)-метиламино]-уксусной кислоты;или фармацевтически приемлемую соль, гидрат или сольват указанных соединений.2. Соединение по п.1, представляющее собой изопропиловый эфир [((1R,2S,5R)-2-изопропил-5-метилциклогексанкарбонил)-амино]-уксусной кислоты или его фармацевтически приемлемую соль.3. Соединение по п.1, представляющее собой изопропиловый эфир [((1R,2S,5R)-2-изопропил-5-метилциклогексанкарбонил)-амино]-уксусной кислоты.4. Композиция, содержащая соединение по любому из пп.1-3 и фармацевтически приемлемый носитель, разбавитель или наполнитель.5. Композиция по п.4, представленная в форме жидкости.6. Композиция по п.5, отличающаяся тем, что соединение присутствует в композиции в концентрации от 0,01 до 5% мас./об.7. Композиция по п.4, представленная в форме порошка, таблетки, леденца, ...

Drug composition and its use in therapy

Compounds and compositions

A compound of formula (I) wherein R is an alkylene chain having between 8 and 20 carbon atoms and A is one or more anions having a total charge of -2 or R is a quaternary amine of formula (IA) as defined herein and A is one or more anions having a total charge of -3; R1, R2, R3, R4, R5 and R6 are each independently selected from C1-10 alkyl and H; E is of formula (Ib) as defined herein. The compound may be for use in the treatment of fungal infections and/or bacterial infections. The compound may be for use in the treatment of herpes virus and/or human papilloma virus. A process for producing the compound.

New form of administration of enkephalinase inhibitor

New form of administration of racecadotril

The use of inhibitors of the renin-angiotensin system for the treatment of hypoxia or impaired metabolic function.

It has been found that an inhibitor of the renin-angiotensin system is useful for the treatment or prevention of a condition associated with hypoxia or impaired metabolic function or efficiency. In particular, it may be used in connection with therapy of stroke or its recurrence, the acute treatment of mycocardial infarction, and the treatment or prevention of wasting or cachexia, and is thus useful in treatment of the symptoms and signs of ageing. It may also be used to enchance function in healthy subjects.

A method for supplying bioavailable methionine to a cow.

The present invention relates to a method for supplying bioavailable methionine to a cow which comprises supplying to the cow an ester of methionine or methionine amide and/or an ester of the hydroxy analogue of methionine or salt thereof.

New form of administration of racecadotril

The use of inhibitors of the renin-angiotensin system for the treatment of hypoxia or impaired metabolic function

NEW FORM OF ADMINISTRATION OF ENKEPHALINASE INHIBITOR

Improvements of implantation rates after in vitro fertilization.

A method is provided for the improvement of implantation rates and/or pregnancy rates in a female mammal, comprising administering to a female mammal in whom prganancy is desired an effective amount of: a nitric oxide synthase substrate, a nitric oxide donor, or both, optionally in combination with, (b)a progestin, and, (c)optionally, in further combination with an estrogen. A method is also provided for fertility control for a female mammal, comprising administering to a female mammal in whom pregnancy is not desired and at risk of becoming pregnant an effective amount of nitric oxide synthase inhibitor in combination with an antiprogestin. Pharmaceutical compositions are also provided ...

New form of administration of racecadotril

New form of administration of enkephalinase inhibitor

Il-8 receptor antagonists

The use of inhibitors of the renin-angiotensin system for the treatment of hypoxia or impaired metabolic function

New form of administration of enkephalinase inhibitor

New form of administration of racecadotril

USE OF INHIBITORS OF THE RENIN ANGIOTENSIN OF SYSTEM

USE OF HEMMERN OF THE RENIN ANGIOTENSIN OF SYSTEM FOR THE TREATMENT OF HYPOXIA OR REDUCED METABOLISM

Racecadotril liquid compositions

Abstract A liquid composition comprising racecadotril and cyclodextrin.

Compounds for treating the remyelination blockade in diseases associated with the expression of HERV-W envelope protein

Abstract The present invention deals with innovative compounds and compositions for preventing and/or treating a newly discovered detrimental mechanism, which blocks the endogenous myelin repair capacity of the adult nervous system (NS) in diseases 5 associated with the expression of HERV-W envelope protein (ENV), in particular of its MSRV subtype. 10574149_1 (GHMatters) P99313.AU.1 ...

Guanidine derivatives as inhibitors of DDAH

Compounds of formula (I) have been found to be useful as inhibitors of DDAH. The present invention thus provides the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of a disease whose pathology is affected by DDAH.

Preventing desensitization of receptors

Theobromine in combination with an expectorant or a mucolytic for use in therapy

An agent comprises theobromine and an expectorant, or an agent comprises theobromine and a mucolytic. The agents of the invention may be used as a combined preparation for simultaneous, sequential or separate use in the therapy of cough.

A method for supplying bioavailable methionine to a cow

Methods for treating fibromyalgia syndrome

The invention is directed to a method of treating fibromyalgia syndrome in a subject, comprising administering a therapeutically effective amount of a carbamoyl compound, or pharmaceutically acceptable salt thereof.

Compounds useful in the treatment of neurofibromatosis

SEVERE SEPSIS PREVENTIVE THERAPEUTIC AGENT

INOS-inhibitory compositions and their use as breast cancer therapeutics

Disclosed are methods for treating one or more mammalian cancers, and in particular, methods for treating human breast cancer employing one or more iNOS pathway inhibitory compounds in combination with one or more selected antihypertensive agents, including calcium channel antagonists,or in combination with one or more conventional chemotherapeutic or anti-cancer regimens. Also disclosed are particular therapeutic formulations including these compositions, and methods for their use in treating refractory, metastatic, and relapsed cancers, and for managing or reversing treatment resistance in human triple-negative breast cancers in particular.

Racecadotril liquid compositions

A liquid composition comprising racecadotril and cyclodextrin.

Pharmaceutical composition comprising (1r,4r)-6'-fluoro-N,N-dimethyl-4-phenyl-4',9'-dihydro-3'H-spiro[cyclohexane-1,1'-pyrano'[3,4,b]indol]-4-amine and paracetamol or propacetamol

The invention relates to a pharmaceutical composition comprising a first pharmacologically active ingredient selected from (1r,4r)-6'-fluoro-N,N-dimethyl-4-phenyl-4',9'-dihydro-3'H-spiro[cyclohexane-1,1'-pyrano[3,4,b]indol]-4-amine and the physiologically acceptable salts thereof, and a second pharmacologically active ingredient selected from paracetamol and propacetamol.

[((1R,2S,5R)-2-isopropyl-5-methyl-cyclohexanecarbonyl)-amino]-acetic acid isopropyl ester and related compounds and their use in therapy

The present invention pertains generally to the field of coolants and medical therapy. More particularly, the present invention relates to certain anti-nociceptive agents, such as [((1R,2S,5f?)-2-isopropyl-5-methyl-cyclohexanecarbonyl)-amino]-acetic acid isopropyl ester, that are potent and long-acting and selectively cooling for non-keratinized epithelial tissues as compared to keratinized epithelial tissues, and are useful, for example, for the treatment of (e.g., the alleviation of symptoms of; the amelioration of) sensory discomfort of non-keratinized stratified epithelial (NKSE) tissue; and so for treatment of: sensory discomfort of an ocular surface, an eyelid, a margin of an eyelid, an anterior part of an eyeball, a conjunctiva, a lachrymal system, a pre-corneal film, or a cornea, a lining of the oral cavity, an internal portion of the lips, a pharyngeal surface, an esophageal surface, or an anogenital surface; eye discomfort, e.g., caused by extended wear of contact lenses, by eye ...

Tyrosine hydroxylase inhibitors for treating intestinal hyperpermeability

The present invention provides methods, compositions, and kits for treating intestinal hyperpermeability in a subject in need thereof, including conditions such as hyperglycemia and underlying diseases such as diabetes, autism, fibromyalgia, inflammatory bowel disease (IBD), graft versus host disease (GVHD), HIV/ AIDS, multiple organ dysfunction syndrome, irritable bowel syndrome (IBS), celiac disease, eczema, psoriasis, acute pancreatitis, Parkinson's disease, depression, chronic fatigue syndrome, asthma, multiple sclerosis, arthritis, ankylosing spondylitis, nonalcoholic fatty liver disease, alcoholic cirrhosis, environmental enteropathy, or kwashiorkor.

Racecadotril lipid compositions

A lipid composition comprising racecadotril, at least one surfactant and a lipid.

(n)-substituted amino acids, antioxidant pharmaceutical compositions containing same and methods using same

Treatment of erectile dysfunction in diabetes patients

Anti-inflammatory agents

Therapeutic uses for nitric oxide inhibitors

AMINO ACID COMPOSITION FOR IMPROVING GLUCOSE TOLERANCE

Disclosed are compositions, including low-calorie beverages or liquids, comprising isoleucine, leucine, valine, cysteine, and methionine, in specified amounts, weight ratios, or both. The compositions are especially useful in treating individuals afflicted with impaired glucose tolerance or diabetes.

CHEMICAL COMPOUNDS

Compounds of formula (I) have been found to be useful as inhibitors of DDAH. The present invention thus provides the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of a disease whose pathology is affected by DDAH.

SUBSTITUTED GLYCINE DERIVATIVES FOR USE AS MEDICAMENTS

The compounds of formula (I) are substituted glycine derivatives useful in the treatment of epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, arthritis, neuropathological disorders, sleep disorders, visceral pain disorders and gastrointestinal disorders. Processes for the preparation of the final products and intermediates useful in the process are included. Pharmaceutical compositions containing one or more of the compounds are also included. Formula (I) wherein R' is hydroxycarbonyl, a carboxylic acid biostere or prodrug thereof; R3, R3a, R2 and R2a are independently selected from H, C1-C6 alkyl, and Cl-C6 alkoxy Cl-C6 alkyl.

MATERIALS AND METHODS FOR ENHANCED DEGRADATION OF MUTANT PROTEINS ASSOCIATED WITH HUMAN DISEASE

The invention features compositions and methods that are useful for treating or preventing a protein conformation disease in a subject by enhancing the degradation of misfolded proteins in vivo.

TREATMENT OF ISCHEMIC BRAIN INJURIES WITH BRAIN TARGETTED ANTIOXIDANT COMPOUNDS

A method of reducing oxidative stress in the brain of an organism having a blood brain barrier and suffering an ischemic brain injury, the method comprising the step of administering a compound to the organism, the compound having (a) a combination of molecular weight and membrane miscibility properties for permitting the compound to cross the blood brain barrier of the organism; (b) a readily oxidizable chemical group for exerting antioxidation properties; and (c) a chemical make-up for permitting the compound or its intracellular derivative to accumulate within the cytoplasm of cells.

SYNERGISTIC ANTIBACTERIAL EFFECTS OF MAGNOLIA BARK EXTRACT AND L-ARGININE, N-LAUROYL ETHYL ESTER ON PLAQUE BIOFILM

The present disclosure relates generally to oral compositions and methods for inhibiting the formation of plaque biofilm by salivary bacteria, and more particularly, to oral compositions comprising a combination of magnolia bark extract (MBE) and L-arginine, Na-lauroyl ethyl ester (LAE). The oral compositions are useful for improving oral health, including inhibiting the formation of plaque biofilm by salivary bacteria and reducing plaque adherence to teeth.

SULFOPROPANOIC ACID DERIVATIVES FOR TREATING NEURODEGENERATIVE DISORDERS

Provided herein is the use of a compound of Formula (I) or a pharmaceutically acceptable salt thereof, for treating a disease characterized by amyloid and amyloid- like aggregates, e.g., Alzheimer's disease.

CRYSTALLINE SALTS OF 5-METHYL-(6S)-TETRAHYDROFOLIC ACID AND L-VALINE ETHYL ESTER

The present invention refers to a crystalline salt comprising 5-methyl-(6S)-tetrahydrofolic acid and L-valine ethyl ester wherein the molar ratio of 5-methyl-(6S)-tetrahydrofolic acid and L-valine ethyl ester is from 1:0.3 to 1:3.0 (in mol/mol) and/or hydrates and/or solvates thereof as well as to a process of obtaining the same.

SYSTEM AND METHOD FOR TREATING MEIBOMIAN GLAND DYSFUNCTION

Systems and methods of treating meibomian and sebaceous gland dysfunction. The methods include reducing oxygen concentration in the environment of one or more dysfunctional meibomian and sebaceous glands, thereby restoring a hypoxic status of one or more dysfunctional meibomian and sebaceous glands. The reducing of the oxygen concentration is accomplished by restricting blood flow to the one or more dysfunctional meibomian and sebaceous glands and the environment of one or more dysfunctional meibomian sebaceous glands. The restricting of the blood flow is accomplished by contracting or closing one or more blood vessels around the one or more dysfunctional meibomian or sebaceous glands. The methods also include giving local or systemic drugs that lead to the generation of hypoxia-inducible factors in one or more dysfunctional meibomian and sebaceous glands.

SEVERE SEPSIS PREVENTIVE THERAPEUTIC AGENT

The present invention provides an agent for the prophylaxis or treatment of severe sepsis, which contains a compound represented by the formula (I): (see formula I) or, the formula (II): (see formula II) , or a salt thereof or a prodrug thereof, a TLR signal inhibitor containing a non-peptide compound and an agent for the prophylaxis or treatment of organ dysfunction and the like, which contains a TLR signal inhibitory substance.

AMINO ACID COMPOSITION FOR IMPROVING GLUCOSE TOLERANCE

... ²²²Disclosed are compositions, including low-calorie beverages or liquids, ²comprising isoleucine, leucine, valine, cysteine, and methionine, in specified ²amounts, weight ratios, or both. The compositions are especially useful in ²treating individuals afflicted with impaired glucose tolerance or diabetes.² ...

INHIBITION OF DEGRADATION OF EXTRACELLULAR MATRIX

This application realtes to a method of inhibiting the degradation of an extracellular matrix associated with islet beta cells, said method comprising contacting said extracellular matrix with an effective amount of a heparanase inhibitor.

METHODS FOR CANCER AND IMMUNOTHERAPY USING GLUTAMINE ANALOGUES, INCLUDING DON

METHOD FOR PURIFYING CYS-LINKED ANTIBODY-DRUG CONJUGATES

The present invention relates to a method for purifying a mixture of cysteine-linked antibody-drug conjugates, wherein the amount of non-conjugated antibody is in the range of 0-40% by weight, using hydrophobic interaction chromatography (HIC). The mixture is loaded onto a preparative HIC column using a 0.2-1.5 M aqueous salt solution, in which non-conjugated antibody is collected in a flow-through fraction, followed by elution of a purified mixture of cysteine-linked antibody-drug conjugates using a 0-100 mM aqueous salt solution.

METHOD FOR MANUFACTURING NOVEL NITROGEN-CONTAINING COMPOUND OR SALT THEREOF AND MANUFACTURING INTERMEDIATE OF NOVEL NITROGEN-CONTAINING COMPOUND OR SALT THEREOF

Provided are an efficient method for producing a nitrogen-containing compound or salt thereof to be used in the production of a treatment agent for diseases involving an integrin. Also provided is a production intermediate of the same. A method for producing a novel nitrogen-containing compound or salt thereof, said method comprising: (1) a step for obtaining a compound represented by general formula [10] or salt thereof by an amidation reaction; and (2) a step for deprotecting the compound represented by general formula [10] or salt thereof.

NITRIC OXIDE DONOR COMPOUNDS

There are disclosed nitric oxide donor compounds of formula (IIa) (see formula IIa) The subject oxide donor compounds show an improved pharmacological profile with respect to the known nitric oxide donors. The subject nitric oxide donor compounds are useful for treating cardiovascular diseases, inflammation, pain, fever, gastrointestinal disorders, ophthalmic diseases, hepatic disorders, renal diseases, respiratory disorders, immunological diseases, bone metabolism dysfunctions, central and peripheral nervous system diseases, sexual dysfunctions, infectious diseases, for the inhibition of platelet aggregation and platelet adhesion, for treating pathological conditions resulting from abnormal cell proliferation, vascular diseases. The invention also relates to pharmaceutical compositions comprising at least one nitric oxide releasing compounds.

(R)-1,2-PROPANEDIOL FOR USE AS A SOLVENT IN THERAPEUTIC COOLING AGENT COMPOSITIONS

The present invention pertains generally to the field of topical medical therapy, cosmetics, and toiletries. More specifically, the invention relates to the use of a solvent comprising (R)-1,2-propanediol for cooling agents, for example, (R)-2-[((1fl,2S,5R)-2-isopropyl- 5-methyl-cyclohexanecarbonyl)-arnino]-propionic acid n-propyl ester (CPS-410). The invention also relates to cooling agent compositions comprising a cooling agent and,2-propanediol, and methods for their preparation. The invention also relates to the use of such cooling agent compositions in therapy, for example, in the treatment of sensory discomfort, especially sensory discomfort of the skin (e.g., itch). The invention also relates to the use of such cooling agent compositions in cosmetics (e.g., eye make-up products) and toiletries (e.g., after-shave lotion).

METHODS FOR TREATING BIPOLAR DISORDER

The invention is directed to a method of treating bipolar disorder in a subject, comprising administering a therapeutically effective amount of a carbamate compound, or pharmaceutically acceptable salt or amide thereof.

[((1R,2S,5R)-2-ISOPROPYL-5-METHYL-CYCLOHEXANECARBONYL)-AMINO]-ACETIC ACID ISOPROPYL ESTER AND RELATED COMPOUNDS AND THEIR USE IN THERAPY

The present invention pertains generally to the field of coolants and medical therapy. More particularly, the present invention relates to certain anti-nociceptive agents, such as [((1R,2S,5R)-2-isopropyl-5-methyl-cyclohexanecarbonyl)-amino]-acetic acid isopropyl ester, that are potent and long-acting and selectively cooling for non-keratinized epithelial tissues as compared to keratinized epithelial tissues, and are useful, for example, for the treatment of (e.g., the alleviation of symptoms of; the amelioration of) sensory discomfort of non-keratinized stratified epithelial (NKSE) tissue; and so for treatment of: sensory discomfort of an ocular surface, an eyelid, a margin of an eyelid, an anterior part of an eyeball, a conjunctiva, a lachrymal system, a pre-corneal film, or a cornea, a lining of the oral cavity, an internal portion of the lips, a pharyngeal surface, an esophageal surface, or an anogenital surface; eye discomfort, e.g., caused by extended wear of contact lenses, by eye ...

METHOD OF TREATMENT OF HYPOXIA INDUCIBLE FACTOR (HIF)-RELATED CONDITIONS

The present invention relates to methods of treatment of Hypoxia Inducible Factor (HIF)-related conditions, and in particular to methods of treatment of HIF-related conditions comprising the administration of a composition comprising transferrins.

NITRIC OXIDE SYNTHESIS INHIBITORS FOR POTENTIATING THE ACTION OF PRESSOR AGENTS IN CERTAIN HYPOTENSIVE PATIENTS

... 2111345 9300893 PCTABS00019 A method for treatment of an animal for systemic hypotension induced by internal nitric oxide production caused by endotoxin or cytokines. The method involves administering an .alpha.1 adrenergic agonist and an amount of an inhibitor of nitric oxide formation from arginine restoring vascular contractile sensitivity to $(a)1 adrenergic agonists. Preferable NG-substituted arginine (having at least one hydrogen on a guanidino amino group replaced by another atomic or molecular species). The inhibitor is administered to an animal having such induced systemic hypotension. Arginine derivative inhibitors are preferably of the L configuration and include pharmaceutically acceptable addition salts. Treatment of systemic hypotension in a patient which has been induced by chemotherapy with biologic response modifiers such as tumor necrosis factor or interleukin-2 may be likewise accomplished. Treatment of an animal for systemic hypotension induced by endotoxin, or other ...

COMPOUNDS USEFUL IN THE TREATMENT OF NEUROFIBROMATOSIS

The present invention relates to compositions useful in the treatment of benign proliferative disorder neurofibromatosis comprising a farnesyl protein transferase inhibitor. Further contained in this invention are methods of treating benign proliferative disorder neurofibromatosis in a mammal, which methods comprise administering to said mammal, a farnesyl proteine transferase inhibitor.

Procédé de préparation d'un nouveau dérivé de thiamphénicol

PHARMACEUTICAL COMPOSITION, CONTAINING (1R, 4R) - 6 '-FLUORINE-N, N-DIMETHYL-4-PHENYL-4 ', 9 '-DIHYDRO-3 'H-SPIRO[TsIKLOGEKSAN-1.1 '-PYRANO-[3.4 ,B]INDOL]-4-AMINE AND PARACETAMOL OR PROPATsETAMOL

A NEW FORM OF ADMINISTERING OF INHIBITOR ENKEFALINAZY

ADAMANTANOVOE DERIVATIVE AND ITS APPLICATION

RECEPTOR ANTAGONISTS OF IL-AND-8

STABILIZED SOLUTION BASED ON ACTIVE SUBSTANCES, METHOD OF PREPARING STABILIZED SOLUTION ACTIVE SUBSTANCES, PHARMACEUTICAL COMPOSITION BASED ON STABILIZED SOLUTION ACTIVE SUBSTANCES (TWO VERSIONS)

НОВАЯ ФОРМА ВВЕДЕНИЯ РАЦЕКАДОТРИЛА

Настоящее изобретение относится к новой лекарственной форме рацекадотрила в виде таблеток, способу их изготовления и их использованию для лечения диареи.

COMPOUNDS FOR THE TREATMENT OF BLOCKADE REMYELINIZATION IN DISEASES, ASSOCIATED WITH EXPRESSION OF ENVELOPE PROTEIN OF HERV-AND-OF W

НОВАЯ ЛЕКАРСТВЕННАЯ ФОРМА РАЦЕКАДОТРИЛА

Изобретение относится к области фармацевтики и медицины и касается новой лекарственной формы рацекадотрила в виде таблеток, способа их изготовления и их применения при лечении диареи.

THEOBROMINE IN COMBINATION WITH AN EXPECTORANT OR A MUCOLYTIC FOR USE IN THERAPY

COMPOUNDS FOR TREATING THE REMYELINATION BLOCKADE IN DISEASES ASSOCIATED WITH THE EXPRESSION OF HERV-W ENVELOPE PROTEIN

New form of administration of enkephalinase inhibitor

PROPHYLACTIC OR AMELIORATING AGENT FO PIGMENTATION

NEW FORM OF THE INTRODUCTION OF

IL-8 RECEPTOR ANTAGONISTS

BICYCLIC ARYL SPHINGOSINE 1-PHOSPHATE ANALOGS

Application of lauroyl arginine ethyl ester derivative used as feed nutrition energy substance

USE OF ESTERS WITH 1.3 TO-BUTANEDIOL OF N-ACYLATED DERIVATIVES OF AMINO ACID, AS HUMAN SKIN LIGHTENING AGENT

USE Of METHIONINE ESTERS IN ANIMAL NUTRITION

USE OF 3,5-SECO-4-NORCHOLESTANE DERIVATIVES FOR OBTAINING A CYTOPROTECTIVE MEDICAMENT

TRPV1 agonist, methods of preparing the same and uses thereof

The instant disclosure relates to a compound represented by formula I and its stereoisomers, tautomers, solvates, polymorphs, or pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions containing them, and methods for preparing the same, and its medical use. The structure of formula I is as follows:.

COMBINATION OF AN ANTIMUSCARINIC OR AN ANTICHOLINERGIC AGENT AND LIPOIC ACID AND USES THEREOF

ADAMANTANE DERIVATIVE AND USE THEREOF

INOS-INHIBITORY COMPOSITIONS AND THEIR USE AS BREAST CANCER THERAPEUTICS

NEUROPROTECTIVE MODULATION OF NMDA RECEPTOR SUBTYPE ACTIVITIES

In various aspects, the invention provides methods and compositions for modulating NMDA receptor subtype activity, to enhance NR2A-containing NMDA receptor activity relative to NR2B-containing NMDA receptor activity, so as to effect a neuroprotective reduction in excitotoxic NMDA receptor activity.

COMBINED USE OF A FIBRATE AND ORLISTAT FOR THE TREATMENT OF OBESITY

The present invention relates to the use of a fibrate and orlistat to treat patients suffering from obesity.

ANTHELMINTICS FOR PREVENTING PARASITIC INFECTIONS IN HUMANS AND ANIMALS

The invention relates to agents containing specific active ingredients that act as repellents and to their use for preventing humans or animals from being infected with parasitic flatworms (platyhelminths).

(HYDROXYETHYL)UREAS AS INHIBITORS OF ALZHEIMER'S BETA-AMYLOID PRODUCTION

Novel (hydroxyethyl)ureas are described. These compounds are effective inhibitors of certain aspartyl proteases, notably secretases involved in the enzymatic cleavage of amyloid precursor protein (APP) to yield amyloid-β peptide. Methods are provided for administering the novel compunds to treat β-amyloid-associated diseases, notably Alzheimer's disease.

UREA AND SULFAMIDE DERIVATIVES AS TAFIA INHIBITORS

The invention relates to compounds of formula (I) which are inhibitors of activated thrombin-activatable fibrinolysis inhibitor. Said compounds of formula (I) are suitable for producing medicaments used for the prevention, secondary prevention, and treatment of one or several diseases associated with thromboses, embolisms, hypercoagulability, or fibrotic changes.

Preventing or ameliorating agent for pigmentation

An object is to provide an external preparation for skin preferably usable to prevent or ameliorate pigmentation. The object is achieved by providing a preventing or ameliorating agent for pigmentation, consisting of a compound represented by the following general formula (1), an isomer thereof, and/or a pharmacologically acceptable salt thereof, and an external preparation for skin containing the same as a component: [wherein R 1 represents an unsubstituted aromatic group or an aromatic group having any substituent; R 2 represents a hydrogen atom, a linear chain or branched chain alkyl group having a number of carbon atom or atoms of 1 to 4, or an acyl group having a linear or branched alkyl chain having a number of carbon atom or atoms of 1 to 4; and R 3 represents a hydrogen atom or a linear chain or branched chain alkyl group having a number of carbon atom or atoms of 1 to 4.]

Neuroprotective modulation of nmda receptor subtype activities

In various aspects, the invention provides methods and compositions for modulating NMDA receptor subtype activity, to enhance NR2A-containing NMDA receptor activity relative to NR2B-containing NMDA receptor activity, so as to effect a neuroprotective reduction in excitotoxic NMDA receptor activity

COMPOSITIONS AND METHODS FOR TREATMENT OF NEUROPSYCHOLOGICAL DEFICITS

Pharmaceutical compositions and methods for the treatment of neuropsychological impairment in human patients comprising a central nervous system (CNS) stimulant in a daily low-dosage amount, and a micronutrient composition containing acetyl L-carnitine, L-tyrosine, N-acetyl cysteine, and alpha-lipoic acid. The CNS stimulant and micronutrient components may be in admixture for convenient daily oral administration of a low dosage CNS stimulant and micronutrients in the range of bout 60-250 mg acetyl L-carnitine, 50-200 mg L-tyrosine, 60-250 mg N-acetyl cystein, and 25-100 mg alpha-lipoic acid per day. 1. An oral dosage composition for the treatment of neuropsychological impairment , comprising:a central nervous system stimulant in up to a low-dosage amount;60 to 250 mg acetyl L-carnitine;50 to 200 mg L-tyrosine;60 to 250 mg N-acetyl cysteine;25 to 100 mg alpha-lipoic acid.2. The composition of claim 1 , wherein acetyl L-carnitine is present in a range of 90 to 190 mg.3. The composition of claim 1 , wherein acetyl L-carnitine is present in a range of 100 to 150 mg.4. The composition of claim 1 , wherein L-tyrosine is present in a range of 70 to 150 mg.5. The composition of claim 1 , wherein L-tyrosine is present in a range of 80 to 100 mg.6. The composition of claim 1 , wherein N-acetyl cysteine is present in a range of 90 to 190 mg.7. The composition of claim 1 , wherein N-acetyl cysteine is present in a range of 100 to 150 mg.8. The composition of claim 1 , wherein alpha-lipoic acid is present in a range of 35 to 75 mg.9. The composition of claim 1 , wherein alpha-lipoic acid is present in a range of 40 to 60 mg.10. The composition of claim 1 , further comprising about 25 to 100 mg L-taurine.11. The composition of claim 10 , wherein L-taurine is present in a range of 35 to 75 mg.12. The composition of claim 1 , wherein the central nervous system stimulant is atomoxetine HCl in an amount of about 2 mg to 20 mg.13. The composition of claim 1 , wherein the central ...

Anti-Aging Formulations

A dietary supplement based on fucoidan, blue-green algae, phycocyanin and phenylethylamine is fortified with one or more of curcumin, silymarin, resveratrol, astragalus root extract, astragoloside IV, vitamin D3, vitamin C, anhydrous trimethylglycine and brewers yeast to stimulate stem cell production and reduce the rate of telomere reduction or shortening. This can result in the repair of existing body cells and enhance longevity by stimulating the production of new stem cells and maintaining the telomeres on new stem cells as well as existing cells. The dietary supplement supports an increased life span by enhancing metabolic function, activating SIRT-1 anti-aging genes, and encouraging the production of new cells with longer telomeres. 1. A dietary composition for stimulating stem cell production and reducing inflammation , comprising:fucoidan in the amount sufficient for promoting an increase in the circulation of stem cells; andphycocyanin in an amount sufficient for reducing inflammation.2. The composition of claim 1 , wherein said phycocyanin is provided in the form of Arthrospira platensis and wherein claim 1 , said fucoidan comprises from about 10% to about 90% by weight of the combined weight of said fucoidan and said phycocyanin and said phycocyanin comprises from about 10% to about 90% by weight of the combined weight of said fucoidan and said phycocyanin.3. The dietary composition of claim 1 , further comprising blue-green algae.4. The dietary composition of claim 3 , wherein said blue-green algae comprises Apanizominom flos aqua (AFA).5. The dietary composition of claim 1 , further comprising at least one of the group consisting of blue green algae claim 1 , phenylethylamine claim 1 , curcumin claim 1 , silymarin claim 1 , resveratrol claim 1 , astragalus root extract claim 1 , astragoloside IV claim 1 , L-carnosine claim 1 , vitamin D3 claim 1 , vitamin C and anhydrous trimethylglycine.6. The dietary composition of claim 1 , further comprising ...

Use of FAAH Inhibitors for Treating Parkinson's Disease and Restless Legs Syndrome

The present disclosure relates to methods of using fatty acid amide hydrolase (FAAH) inhibitors to treat aspects of Parkinson's disease (PD), restless legs syndrome (RLS) and periodic limb movement disorder (PLMD), the use of FAAH inhibitors for the manufacture of medicaments for use in the treatment of PD, RLS and PLMD, as well as pharmaceutically acceptable compositions comprising FAAH inhibitors for use in the treatment of PD, RLS and PLMD. 182-. (canceled)83. A method of treating or preventing an impulse control disorder (ICD) , dopamine dysregulation syndrome (DDS) or sleep disorder arising from the treatment of a patient suffering from Parkinson's disease (PD) , restless legs syndrome (RLS) or periodic limb movement disorder (PLMD) or combination thereof with a dopaminergic agent , comprising administering a therapeutically effective amount of a FAAH inhibitor , or a therapeutically effective amount of a dopaminergic agent and a therapeutically effective amount of a FAAH inhibitor to said patient.84. The method according to claim 83 , wherein the dopaminergic agent is a dopamine replacement agent claim 83 , a dopamine agonist claim 83 , a dopamine uptake inhibitor or a monoamine oxidase inhibitor.85. The method according to claim 84 , wherein the dopamine replacement agent comprises melevodopa or L-3 claim 84 ,4-dihydroxyphenylalanine (levodopa claim 84 , L-DOPA) claim 84 , or an AADC enzyme inhibitor or both an AADC enzyme inhibitor and a COMT inhibitor.86. The method according to claim 85 , wherein the AADC enzyme inhibitor is carbidopa or benserazide and the COMT inhibitor claim 85 , if present claim 85 , is entacapone or tolcapone.87. The method according to claim 84 , wherein the dopamine agonist is bromocriptine (Parlodel®) claim 84 , pergolide (Permax®) claim 84 , pramipexole (Mirapex®) claim 84 , ropinirole (Requip®) claim 84 , rotigotine (Neupro®) claim 84 , cabergoline (Dostinex®) claim 84 , apomorphine (Apokyn®) claim 84 , lisuride (Dopergine®) or ...

PHARMACEUTICAL COMPOSITION COMPRISING ONE OR MORE FUMARIC ACID ESTERS

A pharmaceutical controlled release composition comprising one or more fumaric acid esters. 1. A pharmaceutical composition comprising as an active substance one or more fumaric acid esters selected from di-(C-C)alkylesters of fumaric acid and mono-(C-C)alkylesters of fumaric acid , or a pharmaceutically acceptable salt thereof , wherein the release of the fumaric acid ester—when subjected to an in vitro dissolution test employing 0.1 N hydrochloric acid as dissolution medium during the first 2 hours of the test and then 0.05 M phosphate buffer pH 6.8 as dissolution medium—is as follows:within the first 2 hours after start of the test from about 0% w/w to about 60% w/w of the fumaric ester contained in the formulation is released, and/orwithin the first 3 hours after start of the test about 75% to about 95% of the total amount of the fumaric acid ester contained in the formulation is released.2. The composition according to claim 1 , wherein the release of the fumaric acid ester—when subjected to an in vitro dissolution test employing 0.1 N hydrochloric acid as dissolution medium during the first 2 hours of the test and then 0.05 M phosphate buffer pH 6.8 as dissolution medium—is as follows:within the first 4 hours after start of the test about 92% to about 100% of the total amount of the fumaric acid ester contained in the formulation is released.3. The composition according to any of and claim 1 , wherein the release of the fumaric acid ester—when subjected to an in vitro dissolution test employing 0.1 N hydrochloric acid as dissolution medium during the first 2 hours of the test and then 0.05 M phosphate buffer pH 6.8 as dissolution medium—is as follows:within the first 5 hours after start of the test about 94% to about 100% of the total amount of the fumaric acid ester contained in the formulation is released.4. The composition according to any of the preceding claims claim 1 , wherein the release of the fumaric acid ester—when subjected to an in vitro ...

Compounds and methods for delivery of prostacyclin analogs

This invention pertains generally to prostacyclin analogs and methods for their use in promoting vasodilation, inhibiting platelet aggregation and thrombus formation, stimulating thrombolysis, inhibiting cell proliferation (including vascular remodeling), providing cytoprotection, preventing atherogenesis and inducing angiogenesis. Generally, the compounds and methods of the present invention increase the oral bioavailability and circulating concentrations of treprostinil when administered orally. Compounds of the present invention have the following formula:

Nitric Oxide Amino Acid Esters for Improving Vascular Circulation, and Prophylaxis or Treatment of a Condition Associated with Impaired Blood Circulation

Use of nitric oxide amino acid esters for improving vascular circulation, and prophylaxis or treatment of a condition associated with impaired blood circulation, such as peripheral vascular disease. The nitric oxide amino acid esters may be co-administered with an antimicrobial in topical or transdermal compositions for improving vascular circulation, and prophylaxis or treatment of a condition associated with impaired blood circulation. 7. (canceled)9. (canceled)10. The method according to claim 1 , wherein said treating is transdermally or topically.11. The method as claimed in claim 1 , wherein said condition associated with impaired blood circulation is chosen from a skin ulcer claim 1 , a decubitus ulcer claim 1 , a mouth ulcer claim 1 , a diabetic foot ulcer claim 1 , a venous insufficiency ulcer claim 1 , a venous ulcer claim 1 , an arterial insufficiency ulcer claim 1 , a neuropathic ulcer claim 1 , a genital ulcer claim 1 , a sore claim 1 , a wound claim 1 , a peripheral vascular disease claim 1 , an atherosclerosis claim 1 , Raynaud's phenomenon claim 1 , an erythromelalgia and a gangrene.12. The method according to claim 11 , wherein said peripheral vascular disease is associated with diabetes.13. The method as claimed in claim 1 , wherein said patient has a normotensive blood pressure claim 1 , a hypertensive blood pressure claim 1 , or a hypotensive blood pressure.14. The method as claimed in claim 13 , wherein when blood pressure is a normotensive blood pressure or a hypotensive blood pressure claim 13 , said treating said patient results in a stable blood pressure claim 13 , or wherein when said blood pressure is a hypertensive blood pressure claim 13 , said treating said patient results in a decreased blood pressure or a normotensive blood pressure.1530-. (canceled)34. (canceled)37. (canceled)39. (canceled)40. The composition as claimed in claim 31 , wherein said topical antimicrobial is at least one of a topical antibiotic chosen from amikacin claim ...

BENEFICIAL EFFECTS OF INCREASING LOCAL BLOOD FLOW

The present invention generally relates to the improvement of tissue health by increasing local blood flow. In some aspects of the invention, increased local blood flow is effected by the transdermal delivery of the nitric oxide precursor L-arginine and/or its derivatives alone, or optionally in conjunction with an adjunct such as theophylline. The transdermal delivery is effected, in certain embodiments through the means of a hostile biophysical environment, such as that created by a high ionic strength environment. Various pathological states caused by, or occurring in conjunction with, insufficient blood flow, can be treated using the systems and methods of the invention as described herein. In other embodiments, increased blood flow using the systems and methods of the invention may result in enhanced healing, for example, through greater availability of the constituents of the blood. Examples of conditions which may benefit from increased blood flow include, but are not limited to, erectile dysfunction, hair loss, female sexual dissatisfaction, sagging facial or other body tissue, peripheral vascular disease including claudication, neuropathy, skin ulcers, bone healing, wound healing, viral and bacterial infection, and skin grafting. 140-. (canceled)41. A method , comprising:administering a delivery vehicle to a subject having or at risk of neuropathy, wherein the delivery vehicle comprises a nitric oxide donor and an ionic strength of at least about 0.25 M.42. The method of claim 41 , wherein the nitric oxide donor comprises L-arginine.43. The method of claim 41 , wherein the nitric oxide donor comprises L-arginine hydrochloride.44. The method of claim 41 , wherein the nitric oxide donor comprises a salt of L-arginine.45. The method of claim 41 , wherein the nitric oxide donor comprises a derivative of L-arginine.46. The method of claim 45 , wherein the nitric oxide donor derivative is L-arginine methyl ester.47. The method of claim 45 , wherein the nitric ...

Compounds As L-Cystine Crystallization Inhibitors And Uses Thereof

A method of preventing or inhibiting L-cystine crystallization using the compounds of formula I is disclosed. 2. A method according to wherein the compound is of formula I; and the subscript m is 1-5.3. A method according to wherein the compound is of formula I; and L is —OCH—O—.5. A method according to wherein the compound is of formula I; L is —O—CH—CH—O—; and the subscript t is 1.6. A method according to wherein the compound is of formula I; and the subscript m is 0.9. The method of claim 1 , wherein each of Rand Ris H.10. The method of claim 1 , wherein one of Rand Ris H; and the other is alkyl.11. (canceled)12. The method of claim 1 , wherein each of Rand Ris alkyl.13. (canceled)14. (canceled)15. The method of claim 1 , wherein each of Rand Ris H.16. The method of claim 1 , wherein one of Rand Ris H; and the other is alkyl.17. (canceled)18. The method of claim 1 , wherein each of Rand Ris alkyl.19. (canceled)20. (canceled)21. The method of claim 1 , wherein each of Rand Ris H.22. The method of claim 1 , wherein one of Rand Ris H; and the other is alkyl.23. (canceled)24. The method of claim 1 , wherein each of Rand Ris alkyl.25. (canceled)26. (canceled)27. The method of claim 1 , wherein each of Rand Ris H.28. The method of claim 1 , wherein one of Rand Ris H; and the other is alkyl.29. (canceled)30. The method of claim 1 , wherein each of Rand Ris alkyl.31. (canceled)32. (canceled)35. The method of claim 1 , wherein one of Rand Ris H; and the other is alkyl.36. (canceled)37. The method of claim 1 , wherein one of Rand Ris H; and the other is alkenyl.38. The method of claim 1 , wherein one of Rand Ris H; and the other is alkynyl.39. (canceled)40. The method of claim 1 , wherein one of Rand Ris H; and the other is cycloalkyl.41. (canceled)42. (canceled)43. The method of claim 1 , wherein each of Rand Ris alkyl.44. (canceled)45. The method of claim 1 , wherein each of Rand Ris alkenyl.46. The method of claim 1 , wherein each of Rand Ris alkynyl.47. (canceled)48. ...

EFFERVESCENT FORMULATIONS COMPRISING DEXKETOPROFEN

The present invention relates to water-soluble formulations comprising the active agent dexketoprofen and to a process for production of said formulations. The present invention also relates to pharmaceutical formulations comprising dexketoprofen which is used in symptomatic treatment of mild to moderate pains such as musculoskeletal pains, dysmenorrhoea, toothache, post-operative pains. The formulations are characterized in being in effervescent form. 1. A formulation comprising dexketoprofen , pharmaceutically acceptable solvates , hydrates , salts , amorphous , and/or crystalline forms thereof , characterized in that said formulation is in water-soluble form.2. (canceled)3. The formulation according to claim 1 , characterized in that dexketoprofen is in the form of trometamol salt.4. The formulation according to claim 1 , characterized in that said formulation is in the form of water-soluble powder claim 1 , water-soluble granule claim 1 , water-soluble tablet claim 1 , effervescent powder claim 1 , effervescent granule or effervescent tablet.5. The formulation according to claim 1 , characterized in that the amount of dexketoprofen is in the range of 1 mg to 250 mg or 5 mg to 100 mg.6. (canceled)7. The formulation according to claim 1 , characterized in that said formulation comprises dexketoprofen having d90 value in the range of 250-600 μm claim 1 , 300-500 μm claim 1 , or 350-450 μm.89-. (canceled)10. The formulation according to claim 1 , characterized in that;said formulations are in water soluble tablet or effervescent tablet form; andsaid formulations comprise dexketoprofen having d90 value in the range of 250-600 μm, 300-500 μm, or 350-450 μm.1112-. (canceled)13. The formulation according to claim 1 , wherein said formulation further comprises other pharmaceutically acceptable excipients along with dexketoprofen.14. The formulation according to claim 13 , wherein said formulation comprises excipients such as binder claim 13 , carrier claim 13 , sweetener ...

METHODS FOR TREATING VIRAL DISORDERS

Disclosed are methods of treating viral disorders via the administration of an inducing agent and an anti-viral agent. In one embodiment, the inducing agent and the anti-viral agent are administered for about five days, and the anti-viral agent is subsequently administered without the inducing agent for an additional period of about sixteen days for a total cycle of about 21 days. 1. A method for treating a viral disorder in a subject , comprising:administering to the subject an inducing agent to induce expression of a viral gene product in a virus-infected cell of the subject and an anti-viral agent whose anti-viral activity is directed to the viral gene product expressed, wherein said inducing agent is a HDAC inhibitor, wherein the HDAC inhibitor is a hydroxamic acid derivative, and wherein the subject is not treated with radiation therapy.2. (canceled)3. (canceled)4. The method according to claim 1 , wherein said viral disorder is a neoplasia associated with viral infection.5. The method according to claim 4 , wherein said neoplasia is selected from the group consisting of lymphoma claim 4 , Hodgkin disease claim 4 , Burkitts lymphoma claim 4 , post-transplantation lymphoproliferative disease claim 4 , viral associated lymphoproliferative disease claim 4 , hemophagocytic syndrome claim 4 , nasopharyngeal carcinoma claim 4 , gastric carcinoma claim 4 , or breast cancer.6. The method of claim 1 , wherein the virus of the viral disorder is selected from the group consisting of Epstein-Barr virus (EBV) claim 1 , a herpes virus claim 1 , a Kaposi's-associated human herpes virus (human herpes virus 8) claim 1 , a human immunodeficiency virus (HIV) claim 1 , a papilloma virus claim 1 , a human T-cell or B-cell leukemia/lymphoma virus (HTLV) claim 1 , an adenovirus claim 1 , or a hepatitis virus.7. The method of claim 1 , wherein the inducing agent induces expression of a viral gene product in a virus-infected cell of the subject claim 1 , wherein the viral gene product ...

Use of Inhibitors of the Renin-Angiotensin System

It has been found that inhibitors of the rennin-angiotensin system are useful for the treatment or prevention of conditions associated with hypoxia or impaired metabolic function or efficiency. In particular, they may be used in connection with therapy of stroke or its recurrence, the acute treatment of myocardial infarction, and the treatment or prevention of wasting or cachexia, and are thus useful in treatment of the symptoms and signs of aging. These inhibitors may also be used to enhance function in healthy subjects.

Glycoamino acid and use thereof

An object of the present invention is to provide an amino acid precursor which shows improvement in the properties (particularly water-solubility, stability in water, bitter taste etc.) of amino acid, and can be converted to amino acid in vivo etc. The present invention relates to a compound for an amino acid precursor, which is a compound represented by the formula (I): wherein each symbol is as described in the DESCRIPTION, or a salt thereof.

ANTIMICROBIAL COMPOSITION

The present application describes an antimicrobial composition comprising lauric arginate ethyl ester (LAE) and hydrogen peroxide and the use of this composition for disinfecting and sanitizing different types of surfaces such as food products, human skin or mucosa and hard surfaces as well as a method of stabilizing the composition by including a sequestering agent (citrate salt and/or phosphate salt). 1. An antimicrobial composition comprising:a) Lauric arginate ethyl ester; andb) hydrogen peroxide.2. The antimicrobial composition of claim 1 , further comprising a carrier.3. The antimicrobial composition of claim 1 , further comprising a sequestering agent.4. The composition of claim 1 , wherein concentration said of lauric arginate ethyl ester is of at least about 5 ppm or is from about 0.001% to about 5% w/w or is from about 0.01% to about 2.5% w/w or is from about 0.01% to about 0.1% w/w.59.-. (canceled)10. The composition of claim 1 , wherein said concentration of said hydrogen peroxide is of at least about 5 ppm or is from about 0.001% to about 35% w/w claim 1 , or is from about 0.01% to about 20% w/w or is from about 0.05% to about 15% w/w.1113.-. (canceled)14. The composition of claim 1 , wherein said lauric arginate ethyl ester and said hydrogen peroxide are in a weight ratio of about 1:200 to about 10:1 claim 1 , or of about 1:100 to about 5:1 claim 1 , or of about 1:40 to about 2:1 claim 1 , or of about 1:5 to about 1:1.1517.-. (canceled)18. The composition of claim 14 , wherein said lauric arginate ethyl ester and said hydrogen peroxide are in a weight ratio of about 1:40 claim 14 , or 1:10 claim 14 , or 1:2 claim 14 , or 5:1.1920.-. (canceled)21. The composition of claim 3 , wherein concentration of said sequestering agent is from about 0.0001 to about 2% w/w of the composition.22. The composition of claim 1 , further comprising a stabilizing agent.23. The composition of claim 1 , wherein concentration of said stabilizing agent is from about 0.015% to ...

A PHARMACEUTICAL FORMULATION FOR INTRADUODENAL ADMINISTRATION COMPRISING MELEVODOPA AND CARBIDOPA

A pharmaceutical formulation for intraduodenal administration comprising melevodopa and carbidopa as active ingredients and one or more excipients. Once dispersed in an aqueous medium, melevodopa is completely dissolved, and carbidopa is present as nanoparticles. 1. An aqueous pharmaceutical formulation for intraduodenal administration , comprising carbidopa and melevodopa as active ingredients in a ratio of 1:5 by weight , and one or more excipients , wherein said melevodopa is completely dissolved , and said carbidopa is present as nanoparticles having a volume diameter of 100 to 1000 nm.2. The formulation according to claim 1 , wherein said nanoparticles have a volume diameter of 200 to 900 nm.3. The formulation according to claim 1 , wherein said one or more excipients comprise a component selected from the group consisting of a stabilization agent claim 1 , a wetting agent claim 1 , and mixtures thereof.4. The formulation according to claim 3 , wherein said stabilization agent is selected from the group consisting of hydroxypropyl methylcellulose claim 3 , polyvinylpyrrolidone claim 3 , a vinylpyrrolidone-vinyl acetate copolymer claim 3 , a methacrylic copolymer claim 3 , carboxymethylcellulose claim 3 , a carbomer claim 3 , a plant gum claim 3 , and a plant colloid claim 3 , and mixtures thereof.5. The formulation according to claim 3 , wherein said wetting agent is selected from the group consisting of a pharmaceutically acceptable salt of a fatty acid claim 3 , a poloxamer claim 3 , a polysorbate claim 3 , sorbitan monolaurate claim 3 , and mixtures thereof.6. The formulation according to claim 1 , which further comprises one or more additional excipients selected from the group consisting of an antioxidant claim 1 , a preserving agent claim 1 , a pH regulating agent claim 1 , and mixtures thereof.7. The formulation according to claim 1 , wherein said carbidopa nanoparticles are prepared by a process comprising:i) suspending carbidopa in the presence of one ...

METHOD FOR MANUFACTURING NOVEL NITROGEN-CONTAINING COMPOUND OR SALT THEREOF AND MANUFACTURING INTERMEDIATE OF NOVEL NITROGEN-CONTAINING COMPOUND OR SALT THEREOF

Provided are a method for efficiently manufacturing a nitrogen-containing compound, which is used for manufacturing a treatment agent for integrin-related diseases, or a salt thereof and a manufacturing intermediate of the compound or a salt thereof. 2. The manufacturing method according to claim 1 ,{'sup': '2', 'sub': '1-6', 'wherein Ris a Calkyl group which may be substituted or a benzyl group which may be substituted.'}6. The manufacturing method according to claim 1 ,{'sup': '1', 'sub': '1-6', 'wherein Ris a hydrogen atom, a Calkoxycarbonyl group which may be substituted, an arylsulfonyl group which may be substituted, or a heterocyclic sulfonyl group which may be substituted.'}7. The manufacturing method according to claim 1 ,{'sup': '7', 'sub': '1-6', 'wherein Ris a Calkyl group which may be substituted or a benzyl group which may be substituted.'}8. The manufacturing method according to claim 1 ,wherein the step of deprotecting is a step of deprotecting by using an acid.9. A method for manufacturing a metal complex claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a step of reacting the compound represented by Formula [11] or a salt thereof obtained by the manufacturing method according to with a metal ion.'}11. The compound according to or a salt thereof claim 10 ,{'sup': '8', 'sub': '2-6', 'wherein Ris a Calkyl group which may be substituted.'}15. The compound according to or a salt thereof claim 10 ,{'sup': '1', 'sub': '1-6', 'wherein Ris a hydrogen atom, a Calkoxycarbonyl group which may be substituted, an arylsulfonyl group which may be substituted, or a heterocyclic sulfonyl group which may be substituted.'}16. The compound according to or a salt thereof claim 10 ,{'sup': '7', 'sub': '1-6', 'wherein Ris a Calkyl group which may be substituted or a benzyl group which may be substituted.'}18. The compound according to or a salt thereof claim 17 ,{'sup': '7', 'sub': '1-6', 'wherein Ris a Calkyl group which may be substituted or a ...

METHOD FOR MANUFACTURING NOVEL NITROGEN-CONTAINING COMPOUND OR SALT THEREOF AND MANUFACTURING INTERMEDIATE OF NOVEL NITROGEN-CONTAINING COMPOUND OR SALT THEREOF

A compound represented by Formula [3] or a salt thereof and a method of making the same, 2. The compound according to or a salt thereof claim 1 ,{'sup': '7', 'sub': '1-6', 'wherein Ris a Calkyl group which can be substituted or a benzyl group which can be substituted.'} This application is a Divisional of U.S. application Ser. No. 15/712,815, filed Sep. 22, 2017, which is a Continuation of National Phase of PCT International Application PCT/JP2016/059729 filed on Mar. 25, 2016, which claims priority under 35 U.S.C 119(a) to Japanese Patent Application No. 2015-062306 filed on Mar. 25, 2015. Each of the above application(s) is hereby expressly incorporated by reference, in its entirety, into the present application.The present invention relates to a method for manufacturing a novel nitrogen-containing compound or a salt thereof and a manufacturing intermediate of the compound or a salt thereof.Integrins are a kind of cell adhesion receptors which constitute a family of heterodimeric glycoprotein complexes formed of α and β subunits and are mainly involved in the cell adhesion to extracellular matrix and the transmission of information from extracellular matrix.Among the integrins, integrins ανβand ανβwhich are vitronectin receptors are known to be expressed at a low level on epithelial cells or matured endothelial cells while hyper-expressed in various tumor cells or new blood vessels. The hyper-expression of integrins ανβand ανβis considered to be involved in the exacerbation of cancer such as infiltration or metastasis accompanying tumor angiogenesis and be highly correlated to the malignancy (Nature Reviews cancer, Vol. 10, pp. 9˜23, 2010). It has been revealed that the hyper-expression of integrin is observed in cancer such as head and neck cancer, colorectal cancer, breast cancer, small cell lung cancer, non-small cell lung cancer, glioblastoma, malignant melanoma, pancreatic cancer, and prostatic cancer (Clin. Cancer Res. Vol. 12, pp. 3942˜3949, 2006). ...

METHODS FOR TREATING VIRAL DISORDERS

Disclosed are methods of treating viral disorders via the administration of an inducing agent and an anti-viral agent. In one embodiment, the inducing agent and the anti-viral agent are administered for about five days, and the anti-viral agent is subsequently administered without the inducing agent for an additional period of about sixteen days for a total cycle of about 21 days. 1. A method for treating neoplasia associated with Epstein-Barr virus infection in a subject , comprising administering to the subject an inducing agent to induce expression of a viral gene product in a virus-infected cell of the subject and an anti-viral agent whose anti-viral activity is directed to the viral gene product expressed , wherein said inducing agent induces expression of the viral gene product in the virus-infected cell in less than six treatment cycles , wherein said inducing agent is an HDAC inhibitor , and wherein the HDAC inhibitor is a depsipeptide.2. The method of claim 1 , wherein said neoplasia associated with Epstein-Barr virus infection is a cancer associated with Epstein-Barr virus infection.3. The method of claim 1 , wherein said neoplasia is selected from the group consisting of lymphoma claim 1 , Hodgkin disease claim 1 , Burkitts lymphoma claim 1 , post-transplantation lymphoproliferative disease claim 1 , viral associated lymphoproliferative disease claim 1 , hemophagocytic syndrome claim 1 , nasopharyngeal carcinoma claim 1 , gastric carcinoma claim 1 , and breast cancer.4. The method of claim 1 , wherein said neoplasia is lymphoma.5. The method of claim 1 , wherein the inducing agent induces expression of a viral gene product in a virus-infected cell of the subject claim 1 , wherein the viral gene product is a viral enzyme claim 1 , an oncogene or proto-oncogene claim 1 , a transcription factor claim 1 , a protease claim 1 , a polymerase claim 1 , a reverse transcriptase claim 1 , a cell surface receptor claim 1 , a structural protein claim 1 , a major ...

iNOS-INHIBITORY COMPOSITIONS FOR TREATING CANCER

Disclosed are chemotherapeutic formulations and multicomponent compositions useful in treating one or more mammalian cancers, and in particular, useful in the treatment of human cancers, including melanomas, breast cancers such as triple-negative breast cancer (TNBC), and head or neck cancers. Therapeutically-effective amounts of one or more iNOS pathway-inhibitory compounds, such as L-NMMA, are provided in combination with therapeutically-effective amounts of one or more selected calcium channel antagonists, such as amlodipine, for co-administration with one or more selected chemotherapeutic agents, one or more anti-PD-1 antibodies, and/or one or more doses of ionizing radiation. Also disclosed are pharmaceutical formulations that comprise these compositions, as well as methods for their use in treating refractory, metastatic, and/or relapsed cancers, or, for use in the management or reversal of treatment resistance in one or more types of human cancers, and in particular, cancers such as melanomas, head/neck cancer, and breast cancers, including metastatic forms, and TNBC. 2. The multicomponent drug regimen of claim 1 , wherein the first compound is N-monomethyl-L-arginine (L-NMMA).3. The multicomponent drug regimen of claim 1 , wherein the first calcium channel antagonist is amlodipine.4. The multicomponent drug regimen of claim 1 , wherein the first chemotherapeutic agent comprises: one or more antineoplastic compounds claim 1 , one or more cytotoxic compounds claim 1 , one or more cytostatic compounds claim 1 , one or more cytoreductive compounds claim 1 , or any combination thereof.5. The multicomponent drug regimen of claim 1 , wherein the at least one anticancer agent is selected from the group consisting of cyclophosphamide claim 1 , doxorubicin claim 1 , 5-fluorouracil claim 1 , docetaxel claim 1 , paclitaxel claim 1 , trastuzumab claim 1 , methotrexate claim 1 , epirubicin claim 1 , cis-platin claim 1 , carboplatin claim 1 , vinorelbine claim 1 , ...

METHODS OF IDENTIFYING MODULATORS OF CASTOR1-GATOR2 INTERACTION AND USE OF SAME TO MODULATE mTORC1

The invention relates to methods of identifying compounds that modulate mTORC1 activity in a cell by modulating the activity of CASTOR1, as well as to the use of such identified compounds in the modulation of mTORC1 and the treatment of diseases and conditions characterized by aberrant mTORC1 activity. 2. The method of claim 1 , wherein the first polypeptide comprises CASTOR1 or an isoform of CASTOR1.3. The method of or claim 1 , wherein the second polypeptide or protein complex comprises the CASTOR1-binding fragment of a GATOR2 complex.4. The method of any one of - claim 1 , wherein:the first polypeptide is optionally bound to a first tag;the second polypeptide or protein complex is optionally bound to a second tag;at least one of the first polypeptide or the second polypeptide or protein complex is bound to its corresponding tag; andwherein the step of determining the amount of the first polypeptide associated with the second polypeptide or protein complex: (a) comprises detecting at least one of the first or second tag or a product of the first and second tag; and (b) distinguishes between the first polypeptide associated with the second polypeptide or protein complex and the first polypeptide not associated with the second polypeptide or protein complex.5. The method of claim 4 , wherein:the first tag is present and comprises a first epitope not naturally present in CASTOR1;the second tag is present and comprises a second epitope not naturally present in any GATOR2 complex;detecting the first tag comprises binding a first antibody specific for the first epitope; anddetecting the second tag comprises binding a second antibody specific for the second epitope.6. The method of or claim 4 , wherein one of the first polypeptide or second polypeptide or protein complex is bound to a solid support.7. The method of claim 6 , wherein the binding to the solid support is mediated through the corresponding tag.8. The method of any one of - claim 6 , wherein only one of the ...

mTORC1 MODULATION BY AMINO ACIDS AND USES THEREOF

Disclosed herein are methods for modulating mTORC1 activation in cells or a subject, and related compositions, kits, and agents for use in those methods. Also disclosed is the treatment of diseases and conditions characterized by decreased mTORC1 activation. 1. A combination for increasing mTORC1 activity in a subject to increase muscle mass , increase muscle anabolism , or to treat a disease or condition selected from skeletal muscle atrophy , decreased satiety , abnormally high food intake , hyperphagia , ribosomopathies , cohesinopathies , and conditions that cause reduced myelination of nerves , the combination comprising:a. a first component selected from L-arginine; an mTORC1 agonizing arginine mimetic; and a peptide, non-standard peptide, polypeptide, non-standard polypeptide, protein or non-standard protein any of which is enriched for one or both of L-arginine residues or mTORC1 agonizing arginine mimetic residues;b. a second component selected from L-leucine; an mTORC1 agonizing leucine mimetic; and a peptide, non-standard peptide, polypeptide, non-standard polypeptide, protein or non-standard protein any of which is enriched for one or both of L-leucine residues or mTORC1 agonizing leucine mimetic residues; andc. optionally, a third component selected from L-lysine; an mTORC1 agonizing lysine mimetic; and a peptide, non-standard peptide, polypeptide, non-standard polypeptide, protein or non-standard protein any of which is enriched for one or both of L-lysine residues or mTORC1 agonizing lysine mimetic residues; each component is present in an acceptable form for administration to the subject;', 'any two or all three components may be part of a single composition or a single molecule; and', 'each component is co-administered with one another to the subject., 'wherein2. The combination of claim 1 , wherein the third component is administered to the subject.3. The combination of or claim 1 , wherein at least one of the first component claim 1 , second ...

SYSTEMS AND METHODS FOR MONITORING OF BLOOD LACTATE AND TARGETING OF BLOOD LACTATE VIA NUTRITIONAL SUPPORT

Systems, techniques and methods for estimating the metabolic state or flux, e.g., the body energy state (“BES”) of a patient, are disclosed. The BES provides a deep insight into the nutritional needs of the patient, thus allowing for a sort of exquisite glycemic control with regard to the patient. The invention discloses systems and methods for estimating fractional gluconeogenesis. The invention also discloses systems and methods for estimating and targeting patient blood lactate concentration, both as a target itself and as an intermediate step to estimating and targeting patient fractional gluconeogenesis glucose production. Nutritional support methods and formulations are also disclosed. The invention is suitable for any sort of patient, including those who are injured, such as with traumatic brain injury, ill, or have other conditions that stress the metabolic system. 1. A computer program product comprising a non-transitory computer readable medium having a computer readable program code embodied therein , the product being executable by a processor to perform a method of preventing or treating body wasting in a human patient with traumatic brain injury , the method comprising:receiving a blood lactate concentration of the patient, from a lactate analyzer that has analyzed a blood sample of the patient, the blood lactate concentration received directly from the lactate analyzer or indirectly from the lactate analyzer over a network; andadministering, based on the received blood lactate concentration of the patient, if the blood lactate concentration is less than about 2.0 mM, a nutritional support to the patient.2. The computer program product of wherein the nutritional support comprises a gluconeogenic precursor or a monocarboxylic compound or both.3. The computer program product of wherein the nutritional support comprises one or more salts.4. The computer program product of wherein the nutritional support has a milliosmolality of less than about 1000.5. The ...

Melflufen dosage regimens for cancer

The present invention provides melflufen (melphalan flufenamide; L-Melphalanyl-4-fluoro-L-phenylalanine ethyl ester), or a salt thereof, for use in the treatment or prophylaxis of multiple myeloma, wherein a dosage of melflufen (excluding the mass of any salt) is administered as a parenteral dosage at an infusion rate of 1.0 to 1.8 mg/min. Also provided is melflufen, or a salt thereof, for use in the treatment or prophylaxis of a cancer, for example a solid cancer, wherein a dosage of melflufen is administered as a parenteral dosage at an infusion rate less than 0.8 mg/min (for example 0.3 to 1.0 mg/minor for example 0.3 to 0.8 mg/min).

Biologically Active Cannabidiol Analogs

Biologically active cannabidiol analogs comprising a compound of the formula 2. The pharmaceutical composition for blocking opiate addictive properties according to claim 1 , wherein the opiate is morphine.3. The pharmaceutical composition of claim 1 , wherein the dicarboxylic acid is an organic compound containing two carboxyl functional groups having the formula HOC—R—COH claim 1 , where R is a straight chain or branched aliphatic or aromatic lower alkyl.4. The pharmaceutical composition of claim 1 , wherein the analog is CBD-Di-Alaninate-Di-Hemisuccinate claim 1 , CBD-Divalinate-Di-Hemisuccinate claim 1 , CBD-Mono-Valinate-Mono-Hemisuccinate claim 1 , or CBD-monovalinate-dihemisuccinate.8. The pharmaceutical composition of comprising the biologically active cannabidiol analogs of in a pharmaceutically acceptable carrier.9. The pharmaceutical composition of comprising the biologically active cannabidiol analog of in a pharmaceutically acceptable carrier.10. The pharmaceutical composition of claim 1 , wherein the dicarboxylic acid is malonic acid claim 1 , malic acid claim 1 , glutaric acid claim 1 , succinic acid claim 1 , and phthalic acid.11. The pharmaceutical composition of comprising the biologically active cannabidiol analog of in a pharmaceutically acceptable carrier. This application is a Divisional of U.S. application Ser. No. 16/073,766 filed on Jul. 27, 2018, which is a National Stage Entry of International Application No. PCT/US17/15366, filed on Jan. 27, 2017, which claims priority to U.S. Provisional Application No. 62/289,184, filed on Jan. 29, 2016, the disclosures of which are hereby incorporated by specific reference thereto.The present invention is directed to the development of biologically active cannabidiol analogs capable of being formulated into pharmaceutical compositions, and methods of using such compositions for a pharmacological benefit. In a further embodiment of the present invention biologically active CBD analogs possessed ...

Treatment of Neurodegenerative Conditions by Disruption of Rhes

The invention is directed to the treatment of tauopathic neurodegenerative conditions and the underlying processes thereof. Based on the discovery that Rhes acts as a negative regulator of normal tau clearance, the compositions and methods of the invention may be applied to inhibit Rhes and reduce pathogenic tau aggregation. Rhes may be disrupted by disrupting RAS2D gene expression or reducing the abundance of Rhes protein in neurons. Additionally, post-translational modifications of Rhes may be targeted, including the disruption of Rhes farnesylation by the administration of farnesyltransferase inhibitors. 1. A method of treating frontotemporal dementia in a subject , comprisingadministering to the subject a pharmaceutical composition comprising a farnesyltransferase inhibitor.2. The method of claim 1 , whereinthe farnesyltransferase inhibitor is selected from the group consisting of: lonafarnib, tipifarnib, gingerol, gliotoxin, α-hydroxy farnesyl phosphonic acid, manumycin A, chaetomellic acid A, clavaric acid, FPT Inhibitor I, FPT Inhibitor II, FPT Inhibitor III, FTase Inhibitor I, FTase Inhibitor II, FTI-276 trifluoroacetate salt, GGTI-297, FTI-277 trifluoroacetate salt, and L-744,832 dihydrochloride.3. The method of claim 2 , whereinthe farnesyltransferase inhibitor is lonafarnib.4. A method of treating Alzheimer's disease in a subject claim 2 , comprisingadministering to the subject a pharmaceutical composition comprising a farnesyltransferase inhibitor.5. The method of claim 4 , whereinthe farnesyltransferase inhibitor is selected from the group consisting of: lonafarnib, tipifarnib, gingerol, gliotoxin, α-hydroxy farnesyl phosphonic acid, manumycin A, chaetomellic acid A, clavaric acid, FPT Inhibitor I, FPT Inhibitor II, FPT Inhibitor III, FTase Inhibitor I, FTase Inhibitor II, FTI-276 trifluoroacetate salt, GGTI-297, FTI-277 trifluoroacetate salt, and L-744,832 dihydrochloride.6. The method of claim 5 , whereinthe farnesyltransferase inhibitor is lonafarnib ...

COMPOSITIONS AND METHODS FOR ENHANCING BRAIN FUNCTION USING ACETYL-L-CARNITINE, HUPERZINE A AND GINKGO BILOBA

A nutritional supplement composition is formulated for oral administration and enhances cognitive function. It includes huperzine A, Ginkgo biloba, and acetyl-L-carnitine. The huperzine A, acetyl-L-carnitine, and Ginkgo biloba together account for at least 80 wt % of a dosage unit of the composition. The Ginkgo biloba is about 5.0% to about 12.0%, by weight of the huperzine A, acetyl-L-carnitine and Ginkgo biloba. The Ginkgo biloba and acetyl-L-carnitine are in a ratio of y:z respectively, wherein y is between about 690 and 1,030 for Ginkgo biloba and z is between about 8,000 and 12,000 for acetyl-L-carnitine. 1. A nutritional supplement composition for enhancing cognitive function , comprising:huperzine A;Ginkgo biloba; andacetyl-L-carnitine;wherein the composition is formulated for oral administration such that huperzine A, acetyl-L-carnitine, and Ginkgo biloba together account for at least 80 wt % of a dosage unit of the composition and the Ginkgo biloba is about 5.0% to about 12.0% by weight of the huperzine A, acetyl-L-carnitine and Ginkgo biloba, and the Ginkgo biloba and acetyl-L-carnitine are in a ratio of y:z respectively, wherein y is between about 690 and 1,030 for Ginkgo biloba and z is between about 8,000 and 12,000 for acetyl-L-carnitine.2. The nutritional supplement composition of claim 1 , wherein the huperzine A claim 1 , Ginkgo biloba claim 1 , and acetyl-L-carnitine are in a ratio of x:y:z claim 1 , respectively claim 1 , wherein x is between about 0.85 and about 1.3 for huperzine A claim 1 , y is between about 690 and about 1 claim 1 ,030 for Ginkgo biloba claim 1 , and z is between about 8 claim 1 ,000 and about 12 claim 1 ,000 for acetyl-L-carnitine.3. The nutritional supplement composition of claim 2 , wherein x is between about 0.95 and about 1.20 for huperzine A claim 2 , y is between about 775 and about 945 for Ginkgo biloba claim 2 , and z is between about 9 claim 2 ,000 and about 11 claim 2 ,000 for acetyl-L-carnitine.4. The nutritional ...

COMPOSITIONS AND METHODS FOR ENHANCING BRAIN FUNCTION USING ACETYL-L-CARNITINE, HUPERZINE A, GINKGO BILOBA, AND VITAMIN B COMPLEX

A nutritional supplement composition for enhancing cognitive function includes , acetyl-L-carnitine and huperzine A. The and acetyl-L-carnitine are in a ratio a:b:c respectively such that a as the is between about 690 and 1030, b as the is between about 1,700 and 2,600 and c as the acetyl-L-carnitine is between about 8,000 and 12,000. The composition is formulated for oral administration and the , acetyl-L-carnitine and huperzine A together account for at least 80 wt % of a dosage unit of the nutritional supplement composition. 1. A nutritional supplement composition for enhancing cognitive function , comprising:{'i': 'Ginkgo biloba;'}{'i': 'rhodiola;'}acetyl-L-carnitine; andhuperzine A;{'i': Ginkgo biloba, rhodiola', 'Ginkgo biloba', 'rhodiola', 'Ginkgo biloba, rhodiola, 'wherein the and acetyl-L-carnitine are in a ratio a:b:c respectively such that a as the is between about 690 and 1030, b as the is between about 1,700 and 2,600 and c as the acetyl-L-carnitine is between about 8,000 and 12,000, wherein the composition is formulated for oral administration such that , acetyl-L-carnitine and huperzine A together account for at least 80 wt % of a dosage unit of the nutritional supplement composition.'}2biloba, rhodiola. The nutritional supplement composition of claim 1 , wherein the huperzine A (d) is in a ratio a:b:c:d with the Gingko claim 1 , and acetyl-L-carnitine and the huperzine A is between about 0.85 and 1.3.3Ginkgo biloba, rhodiola. The nutritional supplement composition of claim 1 , comprising a vitamin B complex (e) in a ratio a:b:c:e with the claim 1 , and acetyl-L-carnitine such that e as the Vitamin B complex is between about 860 and 1 claim 1 ,290.4. The nutritional supplement composition of claim 3 , wherein the vitamin B complex comprises vitamins B3 claim 3 , B5 and B6.5Ginkgo biloba, rhodiola. The nutritional supplement composition of claim 1 , comprising a green tea and guarana extract (f) in a ratio a:b:c:f with the claim 1 , and acetyl-L- ...

MODULATORS OF SESTRIN-GATOR2 INTERACTION AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same. 131.-. (canceled)34. The method of claim 33 , wherein the pharmaceutically acceptable composition comprises a pharmaceutically acceptable carrier claim 33 , adjuvant claim 33 , or vehicle. The present invention relates to compounds and methods useful for modulating the Sestrin-GATOR2 interaction thereby selectively modulating mTORC1 activity indirectly. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.The mechanistic target of rapamycin complex 1 (mTORC1) protein kinase is a master growth regulator that senses diverse environmental cues, such as growth factors, cellular stresses, and nutrient and energy levels. When activated, mTORC1 phosphorylates substrates that potentiate anabolic processes, such as mRNA translation and lipid synthesis, and limits catabolic ones, such as autophagy. mTORC1 dysregulation occurs in a broad spectrum of diseases, including diabetes, epilepsy, neurodegeneration, immune response, suppressed skeletal muscle growth, and cancer among others (Howell et al., (2013) Biochemical Society transactions 41, 906-912; Kim et al., (2013) Molecules and cells 35, 463-473; Laplante and Sabatini, (2012) Cell 149, 274-293).Many upstream inputs, including growth factors and energy levels, signal to mTORC1 through the TSC complex, which regulates Rheb, a small GTPase that is an essential activator of mTORC1 (Brugarolas et al., (2004) Genes & Development 18, 2893-2904; Garami et al., (2003) Molecular Cell 11, 1457-1466; Inoki et al., (2003) Genes & Development 17, 1829-1834; Long et al., (2005) Current Biology 15, 702-713; Sancak et al., (2008) Science (New York, N.Y.) 320, 1496-1501; Saucedo et al., (2003) Nature cell biology 5, 566-571; Stocker et al., (2003) Nature cell biology 5, 559-565; Tee et al., (2002) Proc ...

ANTIMICROBIAL COMPOSITION

The present application describes an antimicrobial composition comprising lauric arginate ethyl ester (LAE) and hydrogen peroxide and the use of this composition for disinfecting and sanitizing different types of surfaces such as food products, human skin or amnesia and hard surface as well as a method of stabilizing the composition by including a sequestering agent (citrate salt and/or phosphate salt). 169-. (canceled)70. An antimicrobial composition comprising:a) Lauric arginate ethyl ester;b) hydrogen peroxide; and an additional antimicrobial ingredient selected from the group consisting of an organic acid, an essentials oil, chitosan, a bacteriocin and combinations thereof;', 'an acidulant;', 'a thickening agent;', 'a gelling agent;', 'a foaming agent in a concentration of from about 0.001 to about 20% w/w of said composition;', 'a film forming agent;', 'a potentiator;', 'an antibrowning agent or an antioxidant selected from the group consisting of ascorbic acid or derivatives or isomers thereof, citric acid, malic acid, fumaric acid, lactic acid, succinic acid, pyruvic acid, oxalacetic acid, quinic acid, tartaric acid, alginic acid, pectinic acid, ethylenediaminetetraacetic acid (EDTA), sodium acid pyrophosphate, 4-hexylresorcinol, chitosan, calcium carbonate, calcium sulphate, calcium chloride, calcium phosphate, calcium tartrate, an antioxidant enzyme, and mixtures thereof;', 'a systemic acquired resistance inducer, and', 'combinations thereof., 'at least one of711. The antimicrobial composition of claim , further comprising a carrier.721. The composition of claim , wherein concentration said of lauric arginate ethyl ester is of at least about 5 ppm or is from about 0.001% to about 5% w/w or is from about 0.01% to about 2.5% w/w or is from about 0.01% to about 0.1% w/w.731. The composition of claim , wherein concentration of said hydrogen peroxide is of at least about 5 ppm or is from about 0.001 % to about 35% w/w , or is from about 0.01% to about 20% w/w , ...

Novel high penetration drugs and their compositions thereof for treatment of parkinson diseases

One aspect of the invention provides a composition of novel high penetration compositions (HPC) or a high penetration prodrug (HPP) for treatment of Parkinson's disease. The HPCs/HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPCs/HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

COMPOUNDS AND METHODS FOR DELIVERY OF PROSTACYCLIN ANALOGS

This invention pertains generally to prostacyclin formulations and methods for their use in promoting vasodilation, inhibiting platelet aggregation and thrombus formation, stimulating thrombolysis, inhibiting cell proliferation (including vascular remodeling), providing cytoprotection, preventing atherogenesis and inducing angiogenesis. 2. The method of claim 1 , wherein Rand Rare each H.3. The method of claim 1 , wherein Ris an unbranched alkyl selected from pentyl claim 1 , hexyl claim 1 , heptyl claim 1 , octyl claim 1 , nonyl claim 1 , decyl claim 1 , undecyl claim 1 , and dodecyl.4. The method of claim 1 , wherein Ris a branched alkyl selected from —CH(CH)(CHCH) claim 1 , —CH(CHCH) claim 1 , —C(CH) claim 1 , —C(CHCH) claim 1 , —CHCH(CH) claim 1 , —CHCH(CH)(CHCH) claim 1 , —CHCH(CHCH) claim 1 , —CHC(CH) claim 1 , —CHC(CHCH) claim 1 , —CH(CH)CH(CH)(CHCH) claim 1 , —CHCHCH(CH) claim 1 , —CHCHCH(CH)(CHCH) claim 1 , —CHCHCH(CHCH) claim 1 , —CHCHC(CH) claim 1 , —CHCHC(CHCH) claim 1 , —CH(CH)CHCH(CH) claim 1 , —CH(CH)CH(CH)CH(CH) claim 1 , and —CH(CHCH)CH(CH)CH(CH)(CHCH).5. The method of claim 1 , wherein Ris a cyclic alkyl selected from cyclopentyl claim 1 , cyclohexyl claim 1 , cycloheptyl claim 1 , and cyclooctyl.6. The method of claim 1 , wherein Ris a polycyclic alkyl group.7. The method of claim 6 , wherein the polycyclic alkyl group is adamantyl norbornyl claim 6 , and bicyclo[2.2.2]octyl.8. The method of claim 1 , wherein Ris the substituted alkyl group.9. The method of claim 1 , wherein Ris an unsubstituted alkyl as defined in claim 1 , in which one or more bonds to a carbon(s) or hydrogen(s) are replaced by a bond to an atom selected from F claim 1 , Cl claim 1 , Br claim 1 , and I.10. The method of claim 1 , wherein Ris an unsubstituted alkyl as defined in claim 1 , in which one or more bonds to a carbon(s) or hydrogen(s) are replaced by a bond to an oxygen atom.11. The method of claim 10 , wherein said oxygen atom is in a group selected from hydroxyl ...

MODULATORS OF SESTRIN-GATOR2 INTERACTION AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same. 131.-. (canceled)33. A pharmaceutically acceptable composition comprising a compound according to and a pharmaceutically acceptable carrier claim 32 , adjuvant claim 32 , or vehicle.34. The composition according to in combination with an additional therapeutic agent. The present invention relates to compounds and methods useful for modulating the Sestrin-GATOR2 interaction thereby selectively modulating mTORC1 activity indirectly. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.The mechanistic target of rapamycin complex 1 (mTORC1) protein kinase is a master growth regulator that senses diverse environmental cues, such as growth factors, cellular stresses, and nutrient and energy levels. When activated, mTORC1 phosphorylates substrates that potentiate anabolic processes, such as mRNA translation and lipid synthesis, and limits catabolic ones, such as autophagy. mTORC1 dysregulation occurs in a broad spectrum of diseases, including diabetes, epilepsy, neurodegeneration, immune response, suppressed skeletal muscle growth, and cancer among others (Howell et al., (2013) Biochemical Society transactions 41, 906-912; Kim et al., (2013) Molecules and cells 35, 463-473; Laplante and Sabatini, (2012) Cell 149, 274-293).Many upstream inputs, including growth factors and energy levels, signal to mTORC1 through the TSC complex, which regulates Rheb, a small GTPase that is an essential activator of mTORC1 (Brugarolas et al., (2004) Genes & amp; Development 18, 2893-2904; Garami et al., (2003) Molecular Cell 11, 1457-1466; Inoki et al., (2003) Genes & amp; Development 17, 1829-1834; Long et al., (2005) Current Biology 15, 702-713; Sancak et al., (2008) Science (New York, N.Y.) 320, 1496-1501; Saucedo et al., (2003) Nature cell biology 5, 566-571 ...

THERAPIES FOR SQUAMOUS CELL CARCINOMAS

The present invention relates to the field of cancer therapy. Specifically, provided are methods of neoadjuvant therapies or adjuvant therapies to treat squamous cell carcinoma in a subject with a farnesyltransferase inhibitor (FTI) that include determining whether the subject is likely to be responsive to the FTI treatment based on the H-Ras mutant allele frequency. 1. A method of treating a subject having an H-Ras mutant squamous cell carcinoma (SCC) in conjunction with surgery , comprising administering a therapeutically effective amount of a farnesyltransferase inhibitor (FTI) to the subject , wherein the SCC has an H-Ras mutant allele frequency (AF) that is greater than 20%.2. The method of claim 1 , wherein the H-Ras mutant AF is greater than 25% claim 1 , 30% claim 1 , 35% claim 1 , 40% claim 1 , 45% claim 1 , 50% claim 1 , 55% claim 1 , or 60%.3. The method of or claim 1 , wherein the SCC has an amino acid substitution in H-Ras at a codon selected from a group consisting of G12 claim 1 , G13 claim 1 , Q61 claim 1 , Q22 claim 1 , K117 claim 1 , A146 claim 1 , and any combination thereof.4. The method of any one of to claim 1 , wherein the SCC does not have K-Ras mutation or N-Ras mutation.5. The method of any one of to claim 1 , further comprising administering radiation therapy or chemotherapy to the subject.6. The method of any one of to claim 1 , wherein the FTI is administered before the surgery.7. The method of claim 6 , wherein the FTI reduces tumor burden in the subject by at least 20% claim 6 , at least 30% claim 6 , at least 40% claim 6 , at least 50% claim 6 , at least 60% claim 6 , at least 70% claim 6 , at least 80% claim 6 , at least 90% claim 6 , or at least 95%.8. The method of claim 6 , wherein the FTI converts the SCC from inoperable to operable.9. The method of any one of to claim 6 , wherein the FTI is administered after the surgery.10. The method of claim 9 , wherein the FTI reduces the risk of recurrence after the surgery.11. The method ...

METHOD OF MODULATING RIBONUCLEOTIDE REDUCTASE

A method of modulating ribonucleotide reductase activity in a neoplastic cell includes administering to the cell an amount of a ribonucleotide reductase allosteric modulator (RRAmod), the amount being effective to inhibit neoplastic cell growth. 1. A method of modulating ribonucleotide reductase activity in a neoplastic cell comprising administering to the cell an amount of a ribonucleotide reductase allosteric modulator (RRAmod) , the amount being the amount effective to inhibit neoplastic cell growth.2. The method of claim 1 , the RRAmod modulating ribonucleotide reductase activity by selectively binding at the hexamer interface of RR1.3. The method of claim 2 , the hexamer interface of RR1 comprising an epitope having an amino acid sequence corresponding to SEQ ID NO: 1.4. The method of claim 1 , wherein modulating ribonucleotide reductase activity comprises modulating ribonucleotide reductase mediated catalyzation of ribonucleotides to deoxy ribonucleotides in the neoplastic cell claim 1 , thereby unbalancing the nucleotide pool of DNA precursor molecules required for de novo DNA synthesis.5. The method of claim 1 , the RRAmod comprising a small molecule claim 1 , a peptide claim 1 , a peptidomimetic claim 1 , or an antibody.8. The method of claim 1 , the cell comprising a cancer cell.9. The method of claim 8 , the cancer cell comprising a pancreatic claim 8 , breast claim 8 , lung claim 8 , colon or glyoblastoma cancer cell.10. A method of treating a neoplastic disorder in a subject comprising:administering to neoplastic cells of the subject a therapeutically effective amount of a pharmaceutical composition, the composition comprising a ribonucleotide reductase allosteric modulator (RRAmod), the therapeutically effective amount being the amount to inhibit neoplastic cell growth in the subject.11. The method of claim 10 , the RRAmod modulating ribonucleotide reductase activity by selectively binding to the hexamer interface of RR1.12. The method of claim 11 , ...

Blood lactate range targets and nutritional formulations and protocols to support patients

Systems, techniques and methods for estimating the metabolic state or flux, e.g., the body energy state (“BES”) of a patient, are disclosed. The BES provides a deep insight into the nutritional needs of the patient, thus allowing for a sort of exquisite glycemic control with regard to the patient. The invention discloses systems and methods for estimating fractional gluconeogenesis. The invention also discloses systems and methods for estimating and targeting patient blood lactate concentration, both as a target itself and as an intermediate step to estimating and targeting patient fractional gluconeogenesis glucose production. Nutritional support methods and formulations are also disclosed. The invention is suitable for any sort of patient, including those who are injured, such as with traumatic brain injury, ill, or have other conditions that stress the metabolic system.

ANTIMICROBIAL COMPOUNDS AND METHODS OF USE

The present disclosure provides antimicrobial compounds, compositions comprising such antimicrobial compounds, and methods of their use, in particular, antibacterial compounds and antifungal compounds. In certain aspects, the antimicrobial compounds are effective against pathogens of hospital-acquired infections. In certain aspects, the antimicrobial compounds are effective against pathogens that are resistant to antibiotics. The antimicrobial compounds can be used in antibacterial compositions, antifungal compositions, antiseptic compositions and disinfectant compositions. The antimicrobial compounds can be used as adjuncts in antibacterial compositions and antifungal compositions. 2. A composition comprising the compound of and a pharmaceutically acceptable excipient.3. The composition of further comprising an active pharmaceutical ingredient.4. The composition of further comprising an additive.5. The composition of wherein the additive is at least one of a fragrance claim 4 , an emulsifier claim 4 , a stabilizer and a preservative.6. The composition of wherein the composition is provided in an unit dosage form.7. The composition of wherein the unit dosage form is a tablet claim 6 , a pill claim 6 , a capsule claim 6 , a powder claim 6 , a granule claim 6 , a sterile parenteral solution or a sterile parenteral suspension claim 6 , a metered aerosol spray claim 6 , a metered liquid spray claim 6 , a drop claim 6 , an ampoule claim 6 , an auto-injector device claim 6 , or a suppository.8. The composition of formulated for inhalation claim 7 , oral claim 7 , parenteral claim 7 , intranasal claim 7 , sublingual or rectal administration. This application claims benefit under 35 U.S.C. §119 of U.S. Utility application Ser. No. 13/835,619, filed Mar. 15, 2013 and U.S. Provisional Application Ser. No. 61/737,761, filed Dec. 15, 2012, the contents of which are hereby incorporated by references.1. Field of the InventionThe present disclosure relates to antimicrobial ...

MODULATORS OF SESTRIN-GATOR2 INTERACTION AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same. 131.-. (canceled)33. A pharmaceutically acceptable composition comprising a compound according to claim 32 , and a pharmaceutically acceptable carrier claim 32 , adjuvant claim 32 , or vehicle.34. A method for treating depression in a patient in need thereof claim 33 , comprising the step of administering to said patient the composition of . The present invention relates to compounds and methods useful for modulating the Sestrin-GATOR2 interaction thereby selectively modulating mTORC1 activity indirectly. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.The mechanistic target of rapamycin complex 1 (mTORC1) protein kinase is a master growth regulator that senses diverse environmental cues, such as growth factors, cellular stresses, and nutrient and energy levels. When activated, mTORC1 phosphorylates substrates that potentiate anabolic processes, such as mRNA translation and lipid synthesis, and limits catabolic ones, such as autophagy. mTORC1 dysregulation occurs in a broad spectrum of diseases, including diabetes, epilepsy, neurodegeneration, immune response, suppressed skeletal muscle growth, and cancer among others (Howell et al., (2013) Biochemical Society transactions 41, 906-912; Kim et al., (2013) Molecules and cells 35, 463-473; Laplante and Sabatini, (2012) Cell 149, 274-293).Many upstream inputs, including growth factors and energy levels, signal to mTORC1 through the TSC complex, which regulates Rheb, a small GTPase that is an essential activator of mTORC1 (Brugarolas et al., (2004) Genes & Development 18, 2893-2904; Garami et al., (2003) Molecular Cell 11, 1457-1466; Inoki et al., (2003) Genes & Development 17, 1829-1834; Long et al., (2005) Current Biology 15, 702-713; Sancak et al., (2008) Science (New York, N ...

4-PHENYLBUTYRIC ACID DERIVATIVES

A 4-phenylbutyric acid derivative of Formula (1), 121-. (canceled)23. The method according to claim 22 , wherein the disease is an inflammatory bowel disease.24. The method according to claim 23 , wherein the disease is Crohn's disease.25. The method according to claim 23 , wherein the disease is ulcerative colitis.26. The method according to claim 22 , wherein the disease is an inflammatory disease of the bile ducts.27. The method according to claim 26 , wherein the disease is primary sclerosing cholangitis.28. The method according to claim 22 , wherein the disease is an inflammatory skin disease.29. The method according to claim 28 , wherein the disease is psoriasis.30. The method according to claim 22 , wherein the disease is recurrent vulvo-vaginitis.31. The method according to claim 22 , wherein the disease is varicose veins.32. The method according to claim 31 , wherein the disease is arteriosclerosis.33. The method according to claim 22 , wherein the disease is a major depressive disorder. The present invention relates to 4-phenylbutyric acid derivatives according to the independent claims.Inflammatory bowel diseases are a group inflammatory conditions of the colon and the small intestine. Crohn's disease and ulcerative colitis are the principle types of inflammatory bowel diseases. It is important to note, however, that Crohn's disease cannot only affect the small intestine but also other parts of the gastrointestinal tract. Ulcerative colitis, on the other hand, primarily affects the colon and the rectum. Despite extensive research, the causes underlying inflammatory bowel diseases are not fully understood. It is increasingly thought that alterations to internal bacteria can contribute to inflammatory bowel diseases, as they seem to arrive as a result of a complex interaction between environmental and genetic factors. Even with various treatments available, inflammatory bowel diseases can cause a significant limitation of the quality of the life of patients ...

Treatment of Neurodegenerative Conditions by Disruption of Rhes

The invention is directed to the treatment of tauopathic neurodegenerative conditions and the underlying processes thereof. Based on the discovery that Rhes acts as a negative regulator of normal tau clearance, the compositions and methods of the invention may be applied to inhibit Rhes and reduce pathogenic tau aggregation. Rhes may be disrupted by disrupting RAS2D gene expression or reducing the abundance of Rhes protein in neurons. Additionally, post-translational modifications of Rhes may be targeted, including the disruption of Rhes farnesylation by the administration of farnesyltransferase inhibitors. 113.-. (canceled)14. A method of treating a tauopathy in a subject , comprisingadministering to the subject a pharmaceutical composition comprising one or more Rhes-disrupting agents.15. The method of claim 14 , whereinthe one or more Rhes-disrupting agents comprises an agent which reduces RASD2 expression in a cell.16. The method of claim 14 , whereinthe one or more Rhes-disrupting agents comprises an agent which reduces Rhes protein abundance in a cell.17. The method of claim 14 , whereinthe one or more Rhes-disrupting agents comprises an inhibitor of Rhes binding to the cell membrane.18. The method of claim 17 , whereinthe inhibitor of Rhes binding to the cell membrane comprises a farnesyltranserase inhibitor.19. The method of claim 18 , whereinthe farnesyltranserase inhibitor is selected from the group consisting of: lonafarnib, tipifarnib, gingerol, gliotoxin, α-hydroxy farnesyl phosphonic acid, manumycin A, chaetomellic acid A, clavaric acid, FPT Inhibitor I, FPT Inhibitor II, FPT Inhibitor III, FTase Inhibitor I, FTase Inhibitor II, FTI-276 trifluoroacetate salt, GGTI-297, FTI-277 trifluoroacetate salt, and L-744,832 dihydrochloride.20. The method of claim 14 , whereinthe tauopathy is selected from the group consisting of Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease, chronic ...

HEPATITIS B ANTIVIRAL AGENTS

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: 11. A pharmaceutical composition claim 1 , comprising a compound or a combination of compounds according to claim 1 , in combination with a pharmaceutically acceptable carrier or excipient.12. A method of treating or preventing an HBV infection in a subject in need thereof claim 1 , comprising administering to the subject a therapeutically effective amount of a compound or a combination of compounds according to .13. The method of claim 12 , further comprising administering to the subject at least one additional therapeutic agent selected from the group consisting of HBV polymerase inhibitors claim 12 , interferon claim 12 , viral entry inhibitors claim 12 , viral maturation inhibitors claim 12 , capsid assembly or core protein inhibitors or modulators claim 12 , reverse transcriptase inhibitors claim 12 , TLR-agonists claim 12 , inducers of cellular viral RNA sensor claim 12 , therapeutic vaccines claim 12 , RNA interence (RNAi) or small interfering RNA (siRNA) and combinations thereof.14. The method of claim 13 , wherein the compound and the at least one additional therapeutic agent are co-formulated.15. The method of claim 13 , wherein the at least one additional therapeutic agent is administered at a lower dose and/or frequency than that which is therapeutically effective when said agent is administered alone. This application is a divisional of U.S. application Ser. No. 15/450,125, filed on Mar. 6, 2017, which claims the benefit of U.S. Provisional Application No. 62/304,671, filed on Mar. 7, 2016, and 62/337,675, filed on May 17, 2016. The entire teachings of the above applications are incorporated herein by reference.The present invention relates generally to novel antiviral agents. Specifically, the present invention relates to compounds which can inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function ...

Nitric oxide releasing amino acid ester for treatment of pulmonary hypertension and other respiratory conditions

There is provided compositions and methods for the treatment of respiratory conditions such as pulmonary hypertension and sickle-cell disease in a patient in need thereof. The composition and method are for treating a patient in need thereof by inhalation of a composition containing amino acid ester compounds comprising at least one nitric oxide releasing group and pharmaceutical salts thereof.

METHOD OF MODULATING RIBONUCLEOTIDE REDUCTASE

A method of modulating ribonucleotide reductase activity in a neoplastic cell includes administering to the cell an amount of a ribonucleotide reductase allosteric modulator (RRAmod), the amount being effective to inhibit neoplastic cell growth. 1. A method of modulating ribonucleotide reductase activity in a neoplastic cell comprising administering to the cell an amount of a ribonucleotide reductase allosteric modulator (RRAmod) , the amount being the amount effective to inhibit neoplastic cell growth.2. The method of claim 1 , the RRAmod modulating ribonucleotide reductase activity by selectively binding at the hexamer interface of RR1.3. The method of claim 2 , the hexamer interface of RR1 comprising an epitope having an amino acid sequence corresponding to SEQ ID NO: 1.4. The method of claim 1 , wherein modulating ribonucleotide reductase activity comprises modulating ribonucleotide reductase mediated catalyzation of ribonucleotides to deoxy ribonucleotides in the neoplastic cell claim 1 , thereby unbalancing the nucleotide pool of DNA precursor molecules required for de novo DNA synthesis.5. The method of claim 1 , the RRAmod comprising a small molecule claim 1 , a peptide claim 1 , a peptidomimetic claim 1 , or an antibody.8. The method of claim 1 , the cell comprising a cancer cell.9. The method of claim 8 , the cancer cell comprising a pancreatic claim 8 , breast claim 8 , lung claim 8 , colon or glyoblastoma cancer cell.10. A method of treating a neoplastic disorder in a subject comprising:administering to neoplastic cells of the subject a therapeutically effective amount of a pharmaceutical composition, the composition comprising a ribonucleotide reductase allosteric modulator (RRAmod), the therapeutically effective amount being the amount to inhibit neoplastic cell growth in the subject.11. The method of claim 10 , the RRAmod modulating ribonucleotide reductase activity by selectively binding to the hexamer interface of RR1.12. The method of claim 11 , ...

Assays, Methods and Means

A novel class of hydroxylases is described having the amino acid sequence of SEQ ID NO: 2, 4, 6 and 8, and variants and fragments thereof having HIF hydroxylation activity. The polypeptides of the invention have in particular prolyl hydroxylase activity. An assay method monitors the interaction of the HIF hydroxylase with a substrate. Modulators of HIF hydroxylase are provided for use in the treatment of a condition associated with increased or decreased HIF levels or activity or for the treatment of a condition where it is desirable to modulate HIF levels or activity. 155-. (canceled)56. A method of treatment of a hypoxic condition by administering a substance that inhibits the hydroxylation of one or more prolyl residues of a human HIF-α protein mediated by a HIF prolyl hydroxylase , wherein that substance has been identified as inhibiting such hydroxylation by means of an assay comprisingcontacting a HIF prolyl hydroxylase and a substrate of the hydroxylase under a condition in which the hydroxylase interacts with the substrate, in the presence or absence of a test substance; and 'wherein the HIF prolyl hydroxylase is chosen from (1) the amino acid sequence of SEQ ID NO: 2, 4, 6 or 8; and (2) a fragment thereof containing a β-barrel jelly roll structure and having HIF hydroxylase activity.', 'determining the interaction, or lack of interaction of, the hydroxylase and the substrate by measuring the hydroxylase activity of the hydroxylase;'}57. The method of claim 56 , wherein the HIF prolyl hydroxylase used in the assay contains the motif HXD[X]H claim 56 , where X is any amino acid and n is any number between 1 and 200 claim 56 , and where the HXD portion of the HXD[X]H motif is on the second strand of the β-barrel jelly roll structure.58. The method of claim 57 , wherein the HIF prolyl hydroxylase used in the assay contains the sequence M(X)HXD(X)D(X)Y(X)L(X)P(X)D(X)HXV(X)R where X is any amino acid residue.59. The method of claim 57 , wherein the HIF prolyl ...

Solid pharmaceutical dosage form for release of at least one active pharmaceutical ingredient in the oral cavity

Solid pharmaceutical dosage form for the release of at least one Active Pharmaceutical Ingredient (API) in the oral cavity comprising a core coated by at least one film coating. The core comprises at least one API. One or more organoleptically disturbing sensations induced by one or several of the APIs and/or of inactive components of the solid pharmaceutical dosage form is/are reduced by constituents of said film coating. Said constituents comprise at least one film-forming polymer and at least one flavoring agent or at least one sweetener.

Pharmaceutical Composition Comprising (1r,4r)-6'-fluoro-N, N-dimethyl-4-phenyl-4',9' -dihydro-3'H-spiro[cyclohexane-1,1' -pyrano[3,4,b]indol]-4-amine and Paracetamol or Propacetamol

The invention relates to a pharmaceutical composition comprising a first pharmacologically active ingredient selected from (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine and the physiologically acceptable salts thereof, and a second pharmacologically active ingredient selected from paracetamol and propacetamol. 115.-. (canceled)18. A pharmaceutical dosage form comprising the pharmaceutical composition according to .19. The pharmaceutical dosage form according to claim 18 , which is for oral claim 18 , intravenous claim 18 , intraperitoneal claim 18 , transdermal claim 18 , intrathecal claim 18 , intramuscular claim 18 , intranasal claim 18 , transmucosal claim 18 , subcutaneous claim 18 , or rectal administration.20. The pharmaceutical dosage form according to claim 18 , which provides under in vitro conditions immediate release or controlled release of the first pharmacologically active ingredient claim 18 , the second pharmacologically active ingredient claim 18 , or both the first and second pharmacologically active ingredient.21. A kit comprising a first pharmaceutical dosage form claim 18 , which comprises the first pharmacologically active ingredient according to claim 18 , and a second pharmaceutical dosage form claim 18 , which comprises the second pharmacologically active ingredient according to .22. The kit according to claim 21 , wherein the first and the second pharmaceutical dosage form are adapted for administration by the same pathway.23. The kit according to claim 21 , wherein the first and the second pharmaceutical dosage form are adapted for administration by different pathways.25. The method according to claim 24 , wherein the first pharmacologically active ingredient is in form of a hydrochloride claim 24 , hemicitrate or maleate salt.26. The method according to claim 24 , wherein the pain is chronic pain.27. The method according to claim 24 , wherein the pain is moderate to severe ...

DNP and DNP Prodrug Treatment of Neuromuscular, Neurodegenerative, Autoimmune, Developmental, Traumatic Brain Injury, Concussion, Dry Eye Disease, Hearing Loss and/or Metabolic Diseases

A composition and method of treatment of neuromuscular, neuromuscular degenerative, neurodegenerative, autoimmune, developmental, traumatic, hearing loss related, and/or metabolic diseases, including spinal muscular atrophy (SMA) syndrome (SMA1, SMA2, SMA3, and SMA4, also called Type I, II, III and IV), traumatic brain injury (TBI), concussion, keratoconjunctivitis sicca (Dry Eye Disease), glaucoma, Sjogren's syndrome, rheumatoid arthritis, post-LASIK surgery, anti-depressants use, Wolfram Syndrome, and Wolcott-Rallison syndrome. The composition is selected from the group consisting of 2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP, bipartite 2,3-dinitrophenol, 2,4-dinitrophenol, 2,5-dinitrophenol, 2,6-dinitrophenol, 3,4-dinitrophenol, or 3,5-dinitrophenol (2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP) prodrugs; Gemini prodrugs, bioprecursor molecules, and combinations thereof. A dose of the composition for treatment of neurodegenerative diseases may be from about 0.01 mg/kg of body weight to about 50 mg/kg of body weight of the patient in need of treatment. A dose of the composition for treatment of metabolic diseases may be from about 1 mg/70 kg of body weight to about 100 mg/70 kg of body weight of the patient in need of treatment, and a maximum dose per day is about 200 mg/70 kg of body weight of the patient in need of treatment. 146-. (canceled)48. The composition of claim 47 , wherein the prodrug is stable at a pH of 1-2.49. The composition of claim 47 , wherein the prodrug is stable at a pH of 4.5.50. The composition of claim 47 , wherein the prodrug is stable at a pH of 5-9.51. A depot nanoparticle formulation comprising the composition of .52. A method of treatment of neuromuscular diseases claim 47 , neuromuscular degenerative diseases claim 47 , muscle wasting diseases claim 47 , neurodegenerative diseases claim 47 , autoimmune diseases claim 47 , developmental diseases claim 47 , traumatic diseases of CNS claim 47 , hearing loss ...

COMPOSITIONS CONTAINING NITRIC OXIDE AMINO ACID ESTERS AND METHODS FOR IMPROVING SEXUAL PERFORMANCE

Described herein are compositions and methods for enhancing or improving sexual performance or for treating sexual dysfunction or impotence comprising administering an effective amount of: 8. The composition of claim 1 , wherein n=2.9Pausinystalia yohimbe. The composition of claim 1 , wherein the nutraceutical effective to enhance sexual performance is selected from the group consisting of claim 1 , yohimbine claim 1 , alpha-yohimbine claim 1 , and muira puama.10. The composition of wherein the nutraceutical effective to enhance sexual performance is encapsulated in a liposome.18. The method of wherein n=2.19Pausinystalia yohimbe. The method of wherein the nutraceutical effective to enhance sexual performance is selected from the group consisting of claim 11 , yohimbine claim 11 , alpha-yohimbine claim 11 , and muira puama.20. The method of wherein the nutraceutical effective to enhance sexual performance is encapsulated in a liposome.21. The method of wherein the composition is in tablet form.22. The method of wherein the composition is administered sublingually. The present invention relates to compositions and methods for improving sexual performance or treating sexual dysfunction or impotence, and more particularly to compositions and methods for comprising a nitric oxide amino acid ester compound and a nutraceutical effective to enhance sexual performance.Nitric oxide (NO) is synthesized from L-Arginine through the action of the enzyme NOs (nitric oxide synthetase). NO is synthesized by different NOs enzymes: nNOs (neuronal NOs), which is present in the cytoplasm of the parasympathetic nerves, and eNOs (endothelial NOs), found in the endothelium of the blood vessels and trabecular tissue, which mainly seems to bond to the cell membranes. Numerous experiments have demonstrated that stimulation of the parasympathetic nerves leads to the release of NO as a result of direct action by the nerve endings (reaction catalyzed by nNOs) and indirect action resulting from ...

NOVEL ORGANOSELENIUM COMPOUNDS, METHOD FOR PRODUCING SAME, AND PHARMACEUTICAL USES THEREOF IN PARTICULAR AS ANTITUMOR AGENTS

The invention relates to a selenium compound. Said selenium compound has formula (I), where R=alkyl; R=H, RC(=0), ROC(=0), a-aminoacyl, CHSeCHCHCH(NH)C(=0), CHSeCHCHCH(OH)C(=0); X=OH, OR, NH, NRR, α-amino acid, CHSeCHCHCH(COOH)NH—, CHSeCHCHCH(COOH)0-; R=alkyl; R=alkyl, aryl; R=H, alkyl, aryl; Rand Rwhich can together form a 5- or 6-membered cycloalkyl radical which can comprise a heteroatom; provided that when X=NH-terbutyl, R≠C(=0)CH. Said compound can be used as a pharmaceutical substance, in particular as an antitumour substance. 2. The selenium compound according to claim 1 , wherein Rrepresents a methyl claim 1 , ethyl claim 1 , allyl group.3. The selenium compound according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , α-aminoacyls claim 1 , R(C═O) claim 1 , RO(C═O) claim 1 , CHSeCHCHCH(OH)C(═O).4. The selenium compound according to claim 1 , wherein X is selected from the group OH claim 1 , α-amino acid claim 1 , CHSeCHCHCH(COOH)NH— claim 1 , CHSeCHCHCH(COOH)O—.5. The selenium compound according to claim 1 , wherein Rrepresents a methyl claim 1 , ethyl claim 1 , allyl group; Rrepresents R(C═O) claim 1 , RO(C═O) claim 1 , and X represents OH or OR.6. The selenium compound according to claim 1 , wherein the pharmaceutically acceptable acids are selected from the mineral acids such as hydrochloric claim 1 , hydrobromic claim 1 , hydroiodic claim 1 , sulfuric claim 1 , tartaric claim 1 , phosphoric acids; or selected from the organic acids such as formic claim 1 , acetic claim 1 , trifluoroacetic claim 1 , propionic claim 1 , benzoic claim 1 , maleic claim 1 , fumaric claim 1 , succinic claim 1 , citric claim 1 , oxalic claim 1 , glyoxylic claim 1 , aspartic acids claim 1 , alkanesulfonic acids such as methanesulfonic claim 1 , trifluoromethanesulfonic claim 1 , ethanesulfonic claim 1 , arylsulfonic acids such as benzene- and paratoluenesulfonic acids.7. The selenium compound according to claim 1 , wherein the pharmaceutically ...

PHARMACEUTICAL USE AND PHARMACEUTICAL COMPOSITION OF PYRROLOQUINOLINE QUININE, ITS DERIVATIVES AND/OR ITS SALTS

The present invention relates to the use of pyrroloquinoline quinine (PQQ), its derivatives and/or salts for the preparation of drugs for the treatment and/or prevention of endometriosis including adenomyosis, chocolate cyst of ovary, deeply infiltrating endometriosis and other type of endometriosis. In addition, the present invention relates to the use of PQQ in combination with one or more the following antioxidants: N-Acetyl-L-cysteine (NAC), resveratrol, epigallocatechin gallate, vitamin E or vitamin C for the preparation of drugs for inhibiting the proliferation, oxidative stress status, invasion and migration of endometrial stromal cell. The use of PQQ in combination with NAC shows a synergistic effect on inhibiting cell proliferation: significantly inhibiting the proliferation of endometrial stromal cell in vitro; significantly reducing the damaged size of tissue caused by endometriosis in vivo; significantly reducing the infiltration of endometrial stroma and glands; significantly reducing the dose of NAC as well. PQQ is beneficial for fertility, and increases the chances of getting pregnant. PQQ alone or PQQ in combination with NAC generally shows no side effects and will not interfere with pregnancy. 1. A method of treating and/or preventing endometriosis , comprising: administering to a subject suffering therefrom a therapeutically effective amount of Pyrroloquinoline quinine (PQQ) , its derivatives and/or salts.2. The method as described in claim 1 , characterized in that said endometriosis is adenomyosis.3. The method as described in claim 1 , characterized in that said endometriosis is chocolate cyst of ovary.4. The method as described in claim 1 , characterized in that said endometriosis is deeply infiltrating endometriosis.5. A method of inhibiting the proliferation claim 1 , oxidative stress status and invasion claim 1 , and migration of endometrial stromal cell claim 1 , comprising: administering to a subject suffering therefrom a pharmaceutically ...

Compounds and methods for the treatment of neurodegenerative diseases

Novel compounds of formula (II) are disclosed. Compounds of formula (II) comprise ornithine derivatives or compounds that may metabolize to ornithine. Also disclosed are methods for the treatment of neurodegenerative diseases such as Alzheimer's Disease using compounds of formula (II).

[((1R,2S,5R)-2-ISOPROPYL-5-METHYL-CYCLOHEXANECARBONYL)-AMINO]-ACETIC ACID ISOPROPYL ESTER FOR TREATMENT OF CHRONIC COUGH

The present invention pertains generally to the field of therapy. More specifically the present invention pertains to a certain compound, [((1R,2S,5R)-2-isopropyl-5-methyl-cyclohexanecarbonyl)-amino]-acetic acid isopropyl ester (also referred to herein as “AX-8” or “Gly-O-iPr”), as described herein, for use in a method of treatment of the human or animal body by therapy, more specifically, for use in a method of treatment of chronic cough (CC), including, for example, refractory chronic cough (RCC) and idiopathic chronic cough (ICC), as described herein. 130-. (canceled)31. A method of treatment of refractory chronic cough (RCC) or idiopathic chronic cough (ICC) comprising administering to a patient in need of treatment a therapeutically effective amount of a compound that is [((1R ,2S ,5R)-2-isopropyl-5-methyl-cyclohexanecarbonyl)-amino]-acetic acid isopropyl ester , or a pharmaceutically acceptable salt , hydrate , or solvate thereof.32. A method according to claim 31 , wherein:the chronic cough is idiopathic chronic cough (ICC).33. A method according to claim 31 , wherein:the chronic cough is refractory chronic cough (RCC).34. A method according to claim 31 , wherein:the chronic cough is refractory chronic cough (RCC) that persists after assessment and treatment of a cough-related condition.35. A method according to claim 31 , wherein:the chronic cough is refractory chronic cough (RCC) that persists after assessment and treatment of: asthma, eosinophilic bronchitis, post-nasal drip syndrome (PNDS), gastro-oesophageal reflux disease (GORD), bronchiectasis chronic obstructive pulmonary disease (COPD), or idiopathic pulmonary fibrosis (IPF).36. A method according to claim 31 , wherein:the refractory chronic cough (RCC) or idiopathic chronic cough (ICC) is associated with allotussia.37. A method according to claim 31 , wherein:the refractory chronic cough (RCC) or idiopathic chronic cough (ICC) is associated with hypertussia.38. A method according to claim 31 , ...

ERGOTHIONEINE, S-METHYL-ERGOTHIONEINE, AND USES THEREOF

The present invention provides S-methyl-L-ergothioneine for use in diagnosis and/or prognosis. The invention also provides a method for the diagnosis and/or prognosis of a renal disease comprising the step of determining the amount of S-methyl-L-ergothioneine in an isolated test sample of a subject, and methods for deciding or recommending whether to initiate a therapeutic intervention or for determining the efficacy of a therapeutic intervention. It is also herein provided ergothioneine for use in the treatment and/or prevention of a renal lithiasis or an aminoaciduria, and ergothioneine for use in combination therapy. 1. A method of treating and/or preventing a renal lithiasis or an aminoaciduria in a subject in need thereof , comprising administering to the subject a therapeutically effective amount of Ergothioneine.2. The method of claim 1 , wherein the Ergothioneine is administered with a compound selected from the group consisting of an additional cystine-solubilizing agent claim 1 , L-cystine dimethyl ester claim 1 , L-cystine methyl ester claim 1 , L-cystine diamide claim 1 , lipoic acid claim 1 , and a combination thereof.3. The method of claim 1 , wherein the renal lithiasis is cystine lithiasis claim 1 , and/or the aminoaciduria is cystinuria.4. The method of claim 1 , wherein the Ergothioneine is administered in the form of a pharmaceutical composition comprising one or more pharmaceutically acceptable excipients and/or carriers.5. The method of claim 1 , wherein the Ergothioneine is L-ergothioneine.6. The method of claim 1 , wherein the Ergothioneine is administered in a dose from 0.01 to 500 mg/kg body weight per day.7. (canceled)8. (canceled)9. A method for the diagnosis and/or prognosis and treatment of a renal disease in a subject claim 1 , the method comprising the steps of:determining the amount of S-methyl-L-ergothioneine in an isolated test sample of a the subject; andadministering a therapeutically effective amount of Ergothioneine when the ...

N-substituted isopropyldimethyl azulene sulfonamide derivatives, and preparation method and use thereof

The present invention provides an N-substituted isopropyldimethyl azulene sulfonamide derivative as represented by formula (I), and preparation method and uses thereof, wherein R1 is an alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, amino, or a substituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, and amino. The N-substituted isopropyldimethyl azulene sulfonamide derivative can be used in treating gastric ulcer.

Continuous monitoring of blood lactate and ongoing targeting of blood lactate via nutritional support

Systems, techniques and methods for estimating the metabolic state or flux, e.g., the body energy state (“BES”) of a patient, are disclosed. The BES provides a deep insight into the nutritional needs of the patient, thus allowing for a sort of exquisite glycemic control with regard to the patient. The invention discloses systems and methods for estimating fractional gluconeogenesis. The invention also discloses systems and methods for estimating and targeting patient blood lactate concentration, both as a target itself and as an intermediate step to estimating and targeting patient fractional gluconeogenesis glucose production. Nutritional support methods and formulations are also disclosed. The invention is suitable for any sort of patient, including those who are injured, such as with traumatic brain injury, ill, or have other conditions that stress the metabolic system.

Bicyclic aryl sphingosine 1-phosphate analogs

Compounds that have agonist activity at one or more of the S1P receptors are provided. The compounds are sphin-gosine analogs that, after phosphorylation, can behave as agonists at S1P receptors.

Systems and methods for monitoring of blood lactate and targeting of blood lactate via nutritional support

Systems, techniques and methods for estimating the metabolic state or flux, e.g., the body energy state (“BES”) of a patient, are disclosed. The BES provides a deep insight into the nutritional needs of the patient, thus allowing for a sort of exquisite glycemic control with regard to the patient. The invention discloses systems and methods for estimating fractional gluconeogenesis. The invention also discloses systems and methods for estimating and targeting patient blood lactate concentration, both as a target itself and as an intermediate step to estimating and targeting patient fractional gluconeogenesis glucose production. Nutritional support methods and formulations are also disclosed. The invention is suitable for any sort of patient, including those who are injured, such as with traumatic brain injury, ill, or have other conditions that stress the metabolic system. 1. A method of preventing or treating body wasting in a human patient , the method comprising:receiving a blood lactate concentration of the patient, from a lactate analyzer that has analyzed a blood sample of the patient, the blood lactate concentration received directly from the lactate analyzer or indirectly from the lactate analyzer over a network; andbased on the received blood lactate concentration of the patient, if the blood lactate concentration is less than about 2.0 mM, administering a nutritional support to the patient.2. The method of wherein the nutritional support comprises a gluconeogenic precursor or a monocarboxylic compound or both.3. The method of wherein the nutritional support comprises one or more salts.4. The method of wherein the nutritional support comprises a molecular label.5. The method of wherein the nutritional support has a milliosmolality of less than about 1000.6. The method of wherein the nutritional support comprises an amino acid.7. The method of wherein the nutritional support comprises one or more of the following: glycerol claim 1 , glycerol tri-lactate ...

COMPOUNDS AND METHODS FOR DELIVERY OF PROSTACYCLIN ANALOGS

This invention pertains generally to prostacyclin formulations and methods for their use in promoting vasodilation, inhibiting platelet aggregation and thrombus formation, stimulating thrombolysis, inhibiting cell proliferation (including vascular remodeling), providing cytoprotection, preventing atherogenesis and inducing angiogenesis. 1. A method of treating pulmonary hypertension , treating peripheral vascular disease , promoting vasodilation , inhibiting platelet aggregation and thrombus formation , stimulating thrombolysis , inhibiting cell proliferation , providing cytoprotection , preventing atherogenesis , or inducing angiogenesis comprising administering to a patient in need thereof a pharmaceutically effective amount of a prodrug of treprostinil , wherein the prodrug converts to treprostinil upon said administration.2. The method of claim 1 , wherein the prodrug has no activity before being converted to treprostinil.3. The method of claim 1 , wherein the prodrug is administered by oral administration.4. The method of claim 1 , wherein the prodrug is administered by ingestion.5. The method of claim 1 , wherein the prodrug is administered by transmucosal administration.6. The method of claim 1 , wherein the prodrug is administered by parenteral administration.7. The method of claim 1 , wherein the prodrug is administered by subcutaneous administration.8. The method of claim 1 , wherein the prodrug is administered by injection.9. The method of claim 8 , wherein the injection is a bolus injection.10. The method of claim 8 , wherein the injection is continuous infusion.11. The method of claim 8 , wherein the injection is an intravenous injection.12. The method of claim 1 , wherein the prodrug is administered by duodenal administration.13. The method of claim 1 , which is a method of treating pulmonary hypertension.14. The method of claim 1 , wherein the prodrug is an ester of treprostinil.15. The method of claim 14 , which is a method of treating pulmonary ...

COMPOUNDS AND METHODS FOR DELIVERY OF PROSTACYCLIN ANALOGS

This invention pertains generally to prostacyclin formulations and methods for their use in promoting vasodilation, inhibiting platelet aggregation and thrombus formation, stimulating thrombolysis, inhibiting cell proliferation (including vascular remodeling), providing cytoprotection, preventing atherogenesis and inducing 112.-. (canceled)13. A pharmaceutical composition comprising a) an effective amount of treprostinil or a pharmaceutically acceptable salt or ester thereof and b) polysorbate 80.14. The pharmaceutical composition of claim 13 , wherein the pharmaceutical composition is in the form of a powder.15. The pharmaceutical composition of claim 14 , wherein the pharmaceutical composition further comprises a buffer.16. The pharmaceutical composition of claim 13 , wherein the pharmaceutical composition further comprises a buffer.17. The pharmaceutical composition of claim 13 , wherein the pharmaceutical composition comprises a) a pharmaceutically acceptable salt of treprostinil and b) polysorbate 80.18. The pharmaceutical composition of claim 17 , wherein the pharmaceutically acceptable salt is treprostinil sodium.19. The pharmaceutical composition of claim 18 , wherein the pharmaceutical composition is in the form of a powder.20. The pharmaceutical composition of claim 17 , wherein the pharmaceutical composition is in the form of a powder.21. The pharmaceutical composition of claim 17 , wherein the pharmaceutical composition further comprises a buffer.22. The pharmaceutical composition of claim 18 , wherein the pharmaceutical composition further comprises a buffer.23. The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition further comprises a buffer.24. The pharmaceutical composition of claim 20 , wherein the pharmaceutical composition further comprises a buffer. This application is a continuation of U.S. application Ser. No. 16/784,720, filed Feb. 7, 2020, which is a continuation of U.S. application Ser. No. 16/519,491, filed Jul. ...

Antimalarial Enzyme Conjugates, Kits Containing Same, and Methods of Producing and Using Same

A method, composition, and kit for treating a malarial infection in a subject by using an enzyme conjugate comprising a variant cystathione-gamma-lyase and a targeting ligand which binds to erythrocytes infected with Plasmodium pathogens. The variant cystathione-gamma-lyase has methioninase activity. Also disclosed is a method of treating Plasmodium-infected blood by exposing the infected blood with the enzyme conjugate.

Surface-Modified Heavy Metal Nanoparticles, Compositions And Uses Thereof

Surface-modified heavy metal nanoparticles, including a heavy metal core and a coating layer, the coating layer having at least one ligand, conjugated to polyethylene glycol, the at least one ligand is selected from N-acetyl cysteine, albumin, cysteine, methionine, glutathione, amino thiols, thio-carboxylic acids, ammonia, amines, diamines or any combination thereof. Compositions including surface-modified heavy metal nanoparticles and uses thereof in treatment and diagnosis of various conditions.

SYSTEMS AND METHODS FOR MONITORING OF BLOOD LACTATE AND TARGETING OF BLOOD LACTATE VIA NUTRITIONAL SUPPORT

Systems, techniques and methods for estimating the metabolic state or flux, e.g., the body energy state (“BES”) of a patient, are disclosed. The BES provides a deep insight into the nutritional needs of the patient, thus allowing for a sort of exquisite glycemic control with regard to the patient. The invention discloses systems and methods for estimating fractional gluconeogenesis. The invention also discloses systems and methods for estimating and targeting patient blood lactate concentration, both as a target itself and as an intermediate step to estimating and targeting patient fractional gluconeogenesis glucose production. Nutritional support methods and formulations are also disclosed. The invention is suitable for any sort of patient, including those who are injured, such as with traumatic brain injury, ill, or have other conditions that stress the metabolic system. 1. A system for treating body wasting in a human patient with traumatic brain injury , the system comprising:means for analyzing a blood lactate concentration of the patient; and{'b': 2', '0, 'means for administering a nutritional support to the patient, based on the blood lactate concentration of the patient, if the blood lactate concentration is less than about . mM.'}2. The system of wherein the nutritional support comprises a gluconeogenic precursor or a monocarboxylic compound or both.3. The system of wherein the nutritional support comprises one or more salts.41000. The system of wherein the nutritional support has a milliosmolality of less than about .5. The system of wherein the nutritional support comprises an amino acid.6. The system of wherein the nutritional support comprises one or more of the following: glycerol claim 1 , glycerol tri-lactate claim 1 , glycerol tri-acetate claim 1 , arginyl lactate claim 1 , lactate N-acetylcysteine ester claim 1 , pyruvate claim 1 , acetoacetate claim 1 , or beta-hydroxy butyrate.7145. The system of wherein the nutritional support is administered at ...

NEW COMPOSITION CONTAINING BRANCHED-CHAIN AMINO ACIDS

The present invention relates to compositions comprising branched-chain amino acids (BCAA) and the dipeptide L-Alanyl-L-alanine and their use for improving the performance and recovery during physical activity and for the prevention and/or treatment of muscle wasting associated to pathological or age-related conditions. 111-. (canceled)12. A composition comprising branched-chain amino acids (BCCAs) L-Leucine , L-Valine and L-Isoleucine in combination with peptide L-Alanyl-L-alanine.13. The composition according to claim 12 , wherein the weight ratio L-Leucine:L-Valine:L-Isoleucine is between 2:1:1 and 8:1:1.14. The composition according to claim 13 , wherein the weight ratio L-Leucine:L-Valine:L-Isoleucine is 2:1:1 or 4:1:1 or 8:1:1.15. The composition according to claim 12 , wherein the weight ratio L-Leucine:L-Valine:L-Isoleucine:L-Alanyl-L-alanine is between 2:1:1:1 to 2:1:1:3.6.16. The composition according to claim 15 , wherein the weight ratio L-Leucine:L-Valine:L-Isoleucine:L-Alanyl-L-alanine is 2:1:1:2.5 or 2:1:1:2.17. The composition according to claim 12 , which is a dietary supplement.18. The composition according to claim 12 , which is a pharmaceutical composition.19. The composition according to claim 12 , which is packaged for oral administration.20. The composition according to claim 12 , containing the following amounts of BCAAs and dipeptide per unit dose: between 0.6 and 1 g of L-Leucine claim 12 , between 0.3 and 0.5 g of L-Isoleucine claim 12 , between 0.3 and 0.5 g of L-Valine and from 0.5 g to 1.5 g of L-Alanyl-L-alanine.21. The composition according to claim 20 , containing the following amounts of BCAAs and dipeptide per unit dose: 0.8 g of L-Leucine claim 20 , 0.4 g of L-Isoleucine claim 20 , 0.4 g of L-Valine and 0.8 g of L-Alanyl-L-alanine.23. The method according to claim 22 , wherein the pathological condition is selected from the group consisting of neuromuscular degenerative disorders claim 22 , including muscular dystrophy or muscular ...

METHODS AND COMPOSITIONS FOR INHIBITING GLYOXALASE 1 (GLO1)

Methods and compositions are provided for treating or preventing a neurological disease or disorder using an inhibitor of Glyoxalase 1 (GLO1). In some embodiments, the inhibitor is a small molecule. In certain embodiments, the disease or disorder is a sleep disorder, a mood disorder such as depression, epilepsy, an anxiety disorder, substance abuse, substance dependence or substance such as an alcohol withdrawal syndrome. 192-. (canceled)93. A method of treating a condition in a subject comprising administering to the subject a therapeutically effective amount of a composition comprising a Glo1 inhibitor , wherein the condition is an alcohol abuse disorder or alcohol withdrawal syndrome.94. The method of claim 93 , wherein the Glo1 inhibitor is an antibody.95. The method of claim 93 , wherein the Glo1 inhibitor is an inhibitory nucleic acid.96. The method of claim 93 , wherein the Glo1 inhibitor is a molecule having a glutathione structure claim 93 , a 1-hydroxy-6 claim 93 ,7-diphenylpyridin-2-one derivative (3d) claim 93 , a flavonoid claim 93 , a curcumin claim 93 , a benzothiazole derivative claim 93 , a 4-(7-azaindole)-substituted 6-phenyl-N-hydroxypyridones claim 93 , or 4 claim 93 ,6-diphenyl-N-hydroxypyridone.97. The method of claim 93 , wherein the condition is an alcohol abuse disorder.98. The method of claim 93 , wherein the condition is alcohol withdrawal syndrome.99. The method of claim 93 , further comprising administering a second treatment.100. The method of claim 93 , wherein the second treatment comprises benzodiazepines claim 93 , barbiturates claim 93 , clonidine claim 93 , topiramate carbamazepine claim 93 , or clomethiazole (heminevrin).101. The method of claim 93 , wherein the subject is a human.102. The method of claim 93 , wherein the subject has been determined to have an alcohol abuse disorder.103. The method of claim 102 , further comprising monitoring the subject for the alcohol abuse disorder within a week of first administering the ...

CONTINUOUS MONITORING OF BLOOD LACTATE AND ONGOING TARGETING OF BLOOD LACTATE VIA NUTRITIONAL SUPPORT

Systems, techniques and methods for estimating the metabolic state or flux, e.g., the body energy state (“BES”) of a patient, are disclosed. The BES provides a deep insight into the nutritional needs of the patient, thus allowing for a sort of exquisite glycemic control with regard to the patient. The invention discloses systems and methods for estimating fractional gluconeogenesis. The invention also discloses systems and methods for estimating and targeting patient blood lactate concentration, both as a target itself and as an intermediate step to estimating and targeting patient fractional gluconeogenesis glucose production. Nutritional support methods and formulations are also disclosed. The invention is suitable for any sort of patient, including those who are injured, such as with traumatic brain injury, ill, or have other conditions that stress the metabolic system. 1. A method of treating body wasting in a human patient , the method comprising:receiving a blood lactate concentration of the patient, from a lactate analyzer that has analyzed a blood sample of the patient, the blood lactate concentration received directly from the lactate analyzer or indirectly from the lactate analyzer over a network; andbased on the received blood lactate concentration of the patient, if the blood lactate concentration is less than about 2.0 mM, administering a nutritional support to the patient.2. The method of wherein the nutritional support comprises a gluconeogenic precursor or a monocarboxylic compound or both.3. The method of wherein the nutritional support comprises one or more salts.4. The method of wherein the primary or sole illness of the patient is the body wasting.5. The method of wherein the primary cause of the body wasting is nutritional deficit.6. The method of wherein the nutritional support is enteral claim 1 , parenteral claim 1 , or both.7. The method of wherein the nutritional support comprises one or more of the following: glycerol claim 1 , glycerol ...

TOPICAL COMPOSITIONS FOR THE TREATMENT OF DERMATOLOGICAL DISORDERS

The present invention relates to pharmaceutical compositions and methods useful for the treatment of dermatological disorders, and in particular acne vulgaris and skin pigmentation disorders. Pharmaceutical compositions comprising one or more arginine, salicylic acid and/or azelaic acid that are useful for the treatment of dermatological diseases and the symptoms and underlying causes of such dermatological diseases are also disclosed. 1. A pharmaceutical composition comprising a tripartite complex and an anti-melanogenic compound , wherein the tripartite complex consists of L-arginine , azelaic acid , and salicylic acid.2glycyrrhiza glabra. The pharmaceutical composition of claim 1 , wherein the anti-melanogenic compound is selected from the group consisting of glabridin claim 1 , licorice claim 1 , root extract claim 1 , hesperidin claim 1 , kojic acid claim 1 , kojic dipalmitate claim 1 , azelaic acid claim 1 , niacin claim 1 , melanowhite claim 1 , and leukocyte extract.3. The pharmaceutical composition of claim 1 , wherein the anti-melanogenic compound comprises glabridin.4. The pharmaceutical composition of claim 1 ,wherein the composition is in the form of an emulsion, andwherein the emulsion comprising an aqueous phase and an oil phase.5. The pharmaceutical composition of claim 4 ,wherein the emulsion further comprises one or more salts dispersed therein,wherein the salts are selected from the group consisting of a micronized L-arginate salt of salicylic acid, and a micronized L-arginate salt of azelaic acid, andwherein the salts stabilize the emulsion by preventing the oil phase and the aqueous phase from coalescing.6. The pharmaceutical composition of claim 5 , wherein the one or more salts are unsolubilized.7. The pharmaceutical composition of claim 5 , wherein the aqueous phase comprises the micronized L-arginate salt of salicylic acid and the micronized L-arginate salt of azelaic acid.8. The pharmaceutical composition of claim 1 , wherein the L-arginine ...

Racecadotril lipid compositions

A lipid composition comprising racecadotril, at least one surfactant and a lipid.

COMPOUNDS AND METHODS FOR DELIVERY OF PROSTACYCLIN ANALOGS

This invention pertains generally to prostacyclin formulations and methods for their use in promoting vasodilation, inhibiting platelet aggregation and thrombus formation, stimulating thrombolysis, inhibiting cell proliferation (including vascular remodeling), providing cytoprotection, preventing atherogenesis and inducing angiogenesis. 1. A pharmaceutical composition comprising a) treprostinil or a pharmaceutically acceptable salt or ester thereof and b) polysorbate 80.2. The pharmaceutical composition of in the form of a powder.3. The pharmaceutical composition of further comprising a buffer.4. The pharmaceutical composition of further comprising a buffer.5. The pharmaceutical composition of comprising a) a pharmaceutically acceptable salt of treprostinil and b) polysorbate 80.6. The pharmaceutical composition of claim 5 , wherein the pharmaceutically acceptable salt is treprostinil sodium.7. The pharmaceutical composition of in the form of a powder.8. The pharmaceutical composition of in the form of a powder.9. The pharmaceutical composition of further comprising a buffer.10. The pharmaceutical composition of further comprising a buffer.11. The pharmaceutical composition of further comprising a buffer.12. The pharmaceutical composition of further comprising a buffer. This application is a continuation of U.S. application Ser. No. 16/519,491, filed Jul. 23, 2019, which is a continuation of U.S. application Ser. No. 15/875,101, filed Jan. 19, 2018, which is a continuation of U.S. application Ser. No. 15/239,014, filed Aug. 17, 2016, which is a continuation of U.S. application Ser. No. 14/881,379, filed Oct. 13, 2015, which is a divisional of U.S. application Ser. No. 14/710,694, filed May 13, 2015, which is a continuation of U.S. application Ser. No. 14/490,014, filed Sep. 18, 2014, which is a Continuation of U.S. application Ser. No. 13/906,585, filed May 31, 2013, which is a divisional of U.S. application Ser. No. 13/558,757, filed Jul. 26, 2012, which is a ...

Nitric Oxide Amino Acid Esters for Improving Vascular Circulation, and Prophylaxis or Treatment of a Condition Associated with Impaired Blood Circulation

The present document describes transdermal compositions comprising effective amounts of a nitric oxide amino acid ester compound, a skin penetration enhancer is association with a pharmaceutically acceptable carrier. Also described are methods of use for improving vascular circulation, and prophylaxis or treatment of a condition associated with impaired blood circulation, including peripheral vascular diseases. 7. (canceled)9. (canceled)10. The method according to claim 1 , wherein said treating is transdermally or topically.11. The method as claimed in claim 1 , wherein said condition associated with impaired blood circulation is chosen from a skin ulcer claim 1 , a decubitus ulcer claim 1 , a mouth ulcer claim 1 , a diabetic foot ulcer claim 1 , a venous insufficiency ulcer claim 1 , a venous ulcer claim 1 , an arterial insufficiency ulcer claim 1 , a neuropathic ulcer claim 1 , a genital ulcer claim 1 , a sore claim 1 , a wound claim 1 , a peripheral vascular disease claim 1 , an atherosclerosis claim 1 , Raynaud's phenomenon claim 1 , an erythromelalgia and a gangrene.12. The method according to claim 11 , wherein said peripheral vascular disease is associated with diabetes.131. The method as claimed in claim claim 11 , wherein said patient has a normotensive blood pressure claim 11 , a hypertensive blood pressure claim 11 , or a hypotensive blood pressure.14. The method as claimed in claim 13 , wherein when blood pressure is a normotensive blood pressure or a hypotensive blood pressure claim 13 , said treating said patient results in a stable blood pressure claim 13 , or wherein when said blood pressure is a hypertensive blood pressure claim 13 , said treating said patient results in a decreased blood pressure or a normotensive blood pressure.1530.-. (canceled)34. (canceled)37. (canceled)39. (canceled)4142.-. (canceled)43. The composition of claim 31 , further comprising a skin penetration enhancer chosen from a C-Cfatty acid claim 31 , a C-Cfatty alcohol claim ...

COMPOSITIONS AND METHODS FOR ENHANCING BRAIN FUNCTION

A nutritional supplement composition enhances cognitive function and includes huperzine A, vinpocetine, acetyl-L-carnitine, and rhodiola. The composition is formulated for oral administration. The huperzine A, vinpocetine, acetyl-L-carnitine, and rhodiola are in a ratio a:b:c:d: respectively such that a as the huperzine A is between about 0.8 and 1.2, b as vinpocetine is between about 80 and 120, c as rhodiola is about 1,600 and 2,400, and d as the acetyl-L-carnitine is between about 8,000 and 12,000. 1. A nutritional supplement composition for enhancing cognitive function , comprising:huperzine A;at least one of vinpocetine and rhodiola;acetyl-L-carnitine;a vitamin B complex; anda green tea and guarana extract;wherein the composition is formulated for oral administration and one of at least the vinpocetine is present in an amount from about 10 mg to 30 mg and the rhodiola is present in an amount from about 200 mg to 400 mg and the acetyl-L-carnitine is present in an amount from about 1,250 mg to 2000 mg, and the huperzine A, acetyl-L-carnitine, and at least one of the vinpocetine and rhodiola together account for at least 80 wt % of a dosage unit of the composition.2. The nutritional supplement composition of claim 1 , wherein the huperzine A is present in an amount from about 50 mcg to 200 mcg.3. The nutritional supplement composition of claim 1 , wherein the vitamin B complex is present in an amount from about 125 mg to 175 mg.4. The nutritional supplement composition of claim 1 , wherein the huperzine A claim 1 , at least one of vinpocetine and rhodiola claim 1 , acetyl-L-carnitine claim 1 , the Vitamin B complex claim 1 , and the green tea and guarana extract are in a ratio of a:b:c:d:e:f respectively such that a as the huperzine A is between about 0.8 and 1.2 claim 1 , b as the vinpocetine is between about 80 and 120 claim 1 , c as the rhodiola is between about 1600 and 2400 claim 1 , d as the acetyl-L-carnitine is between about 8 claim 1 ,000 and 12 claim 1 , ...

Prodrugs of Compounds that Enhance Antifungal Activity and Compositions of Said Prodrugs

The invention relates to prodrugs for use in the inhibition of histone deacetylase. The prodrugs of the present invention have good aqueous solubility and good aqueous stability. The prodrugs of the invention advantageously are metabolized to the active ingredient in plasma or in the blood stream of a warm-blooded animal. The invention also provides compositions and, and methods for making the prodrugs, and methods for using the prodrugs to treat fungal infections. 1. A compound of the formula{'br': None, 'sup': 2', '2', 'x, 'Cy-L-Ar—Y—C(O)N(R)—Z'} Cy is —H, cycloalkyl, aryl, heteroaryl, or heterocyclyl, any of which is optionally substituted, provided that Cy is not a (spirocycloalkyl)heterocyclyl;', {'sup': '2', 'sub': 1', '6', '2', '6', '2, 'Lis C-Csaturated alkylene or C-Calkenylene, wherein the alkylene or alkenylene optionally is substituted, and wherein one or two of the carbon atoms of the alkylene is optionally replaced by O; NR′, R′ being alkyl, acyl, or hydrogen; S; S(O); or S(O);'}, 'Ar is arylene, wherein said arylene optionally is additionally substituted and optionally is fused to an aryl or heteroaryl ring, or to a saturated or partially unsaturated cycloalkyl or heterocyclic ring, any of which is optionally substituted; and', {'sup': '2', 'Yis a chemical bond or a straight- or branched-chain saturated alkylene, which is optionally substituted, provided that the alkylene is not substituted with a substituent of the formula —C(O)R wherein R comprises an α-amino acyl moiety;'}], 'or a pharmaceutically acceptable salts thereof, wherein'}{'sup': x', '20, 'Ris —H, OH, or —R;'}{'sup': 20', '21, 'Z is —O—Ror —Rwherein'}{'sup': '20', 'claim-text': [{'sup': '10', '—C(O)—R,'}, {'sup': 40', '41, 'sub': 'n', '—C(O)-[C(R)(R)]OP(O)(OH)(OH),'}, {'sup': 31', '40', '41, 'sub': n', '2, '—C(O)N(R)[C(R)(R)]SOOH, or'}, {'sup': 40', '41', '40', '41', '42, 'sub': n', 'n, '—C(O)NH[C(R)(R)]C(O)O[C(R)(R)]R;'}], 'each —Ris'}{'sup': '10', 'claim-text': [{'sup': 40', '41', '42, ...

NITRIC OXIDE DONOR COMPOUNDS

The invention relates to nitric oxide donor compounds and their use for treating cardiovascular diseases, inflammation, pain, fever, gastrointestinal disorders, ophthalmic diseases, hepatic disorders, renal diseases, respiratory disorders, immunological diseases, bone metobolisms dysfunctions, central and peripheral nervous system diseases, sexual dysfunctions, infectious diseases, for the inhibition of platelet aggregation and platelet adhesion, for treating pathological conditions resulting from abnormal cell proliferation, vascular diseases. The invention also relates to compositions comprising at least one nitric oxide releasing compounds of the invention and composition comprising at least one nitric oxide releasing compounds according to the invention and at least one 15 therapeutic agent. 149-. (canceled)53. A medicament comprising a compound according to and one or more pharmaceutically acceptable excipients.54. A pharmaceutical composition comprising a compound according to and one or more pharmaceutically acceptable excipients.55. A composition comprising at least a compound of formula (I) according to and at least one therapeutic agent selected from the group consisting of: anti-inflammatory drugs claim 50 , drugs used to treat cardiovascular diseases claim 50 , drugs for treating ocular diseases claim 50 , and drugs for treating respiratory disorders.56. A medicament comprising the composition according to and one or more pharmaceutically acceptable excipients.57. The composition according to wherein the compound of formula (I) and the at least one therapeutic agent are administered simultaneously or sequentially.58. A pharmaceutical composition comprising the composition according to and one or more pharmaceutically acceptable excipients.77. A medicament comprising a compound according to and one or more pharmaceutically acceptable excipients.78. A method for treating a condition comprising administering a compound according to claim 50 , wherein the ...

Modulators of sestrin-gator2 interaction and uses thereof

The present invention provides compounds, compositions thereof, and methods of using the same.

HEPATITIS B ANTIVIRAL AGENTS

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: 210-. (canceled)11. A pharmaceutical composition comprising a compound according to and a pharmaceutically acceptable carrier or excipient.12. A method of treating or preventing an HBV infection in a subject in need thereof claim 1 , comprising administering to the subject a therapeutically effective amount of a compound or a combination of compounds according to .13. The method of claim 12 , further comprising administering to the subject at least one additional therapeutic agent selected from the group consisting of HBV polymerase inhibitors claim 12 , interferon claim 12 , viral entry inhibitors claim 12 , viral maturation inhibitors claim 12 , capsid assembly or core protein inhibitors or modulators claim 12 , reverse transcriptase inhibitors claim 12 , TLR-agonists claim 12 , inducers of cellular viral RNA sensor claim 12 , therapeutic vaccines claim 12 , RNA interference (RNAi) or small interfering RNA (siRNA) and combinations thereof.14. The method of claim 13 , wherein the compound and the at least one additional therapeutic agent are co-formulated.15. The method of claim 13 , wherein the at least one additional therapeutic agent is administered at a lower dose and/or frequency than that which is therapeutically effective when said agent is administered alone. This application is a continuation of U.S. application Ser. No. 16/715,602, filed on Dec. 16, 2019, which is a continuation application of U.S. application Ser. No. 16/194,608, filed on Nov. 19, 2018, now U.S. Pat. No. 10,538,532, issued on Jan. 21, 2020, which is a divisional of U.S. application Ser. No. 15/450,125, filed on Mar. 6, 2017, now U.S. Pat. No. 10,179,792, issued on Jan. 15, 2019, which claims the benefit of U.S. Provisional Application No. 62/304,671, filed on Mar. 7, 2016, and 62/337,675, filed on May 17, 2016. The entire teachings of the above applications are ...

HEPATITIS B ANTIVIRAL AGENTS

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: 110-. (canceled)11. A pharmaceutical composition claim 16 , comprising a compound according to and a pharmaceutically acceptable carrier or excipient.12. A method of treating or preventing an HBV infection in a subject in need thereof claim 16 , comprising administering to the subject a therapeutically effective amount of a compound according to .13. The method of claim 12 , further comprising administering to the subject at least one additional therapeutic agent selected from the group consisting of HBV polymerase inhibitors claim 12 , interferon claim 12 , viral entry inhibitors claim 12 , viral maturation inhibitors claim 12 , capsid assembly or core protein inhibitors or modulators claim 12 , reverse transcriptase inhibitors claim 12 , TLR-agonists claim 12 , inducers of cellular viral RNA sensor claim 12 , therapeutic vaccines claim 12 , RNA interference (RNAi) or small interfering RNA (siRNA) and combinations thereof.14. The method of claim 13 , wherein the compound and the at least one additional therapeutic agent are co-formulated.15. (canceled)17. The compound of claim 16 , wherein:n at each occurrence is independently 0, 1, or 2;{'sub': '21', 'Rat each occurrence is independently halogen, CN, methyl, methoxy, or cyclopropyl;'}{'sub': '22', 'Ris halogen, CN, methyl, or methoxy;'}{'sub': '23', 'Ris hydrogen or halogen;'}{'sub': 10', '1', '3, 'Each Ris independently hydrogen, halogen, hydroxyl, or optionally substituted C-Calkyl; and'}{'sub': '30', 'Ris hydrogen or an acyl group derived from an amino acid.'}18. The compound of claim 16 , wherein:{'sub': '21', 'Each Ris fluorine;'}{'sub': '22', 'Ris chlorine;'}{'sub': '23', 'Ris hydrogen or fluorine; and'}{'sub': '10', 'Each Ris independently hydrogen, halogen, hydroxyl, hydroxymethyl, fluoromethyl, trifluoromethyl, or methoxymethyl.'}19. The compound of claim 16 , wherein Ris an acyl ...

TOPICAL COMPOSITIONS FOR THE TREATMENT OF DERMATOLOGICAL DISORDERS

The present invention relates to pharmaceutical compositions and methods useful for the treatment of dermatological disorders, and in particular acne vulgaris and skin pigmentation disorders. Pharmaceutical compositions comprising one or more arginine, salicylic acid and/or azelaic acid that are useful for the treatment of dermatological diseases and the symptoms and underlying causes of such dermatological diseases are also disclosed. 1. A method of treating a subject with a dermatological disorder ,wherein the method comprises topically administering to the subject a pharmaceutical composition comprising a tripartite complex and an anti-melanogenic compound;wherein the tripartite complex consists of L-arginine, azelaic acid, and salicylic acid; andwherein the dermatological disorder is selected from the group consisting of post-inflammatory hyperpigmentation (PIH), low skin hydration, excess sebum production, and acne vulgaris.2Glycyrrhiza glabra. The method of claim 1 , wherein the anti-melanogenic compound is selected from the group consisting of glabridin claim 1 , licorice claim 1 , root extract claim 1 , hesperidin claim 1 , kojic acid claim 1 , kojic dipalmitate claim 1 , azelaic acid claim 1 , niacin claim 1 , melanowhite claim 1 , and leukocyte extract.3. The method of claim 1 , wherein the anti-melanogenic compound comprises glabridin.4. The method of claim 1 ,wherein the composition is in the form of an emulsion; andwherein the emulsion comprises an aqueous phase and an oil phase.5. The method of claim 4 ,wherein the emulsion further comprises one or more salts dispersed therein,wherein the salts are selected from the group consisting of a micronized L-arginate salt of salicylic acid, and a micronized L-arginate salt of azelaic acid, andwherein the salts stabilize the emulsion by preventing the oil phase and the aqueous phase from coalescing.6. The method of claim 5 , wherein the one or more salts are un-solubilized.7. The method of claim 5 , wherein the ...

BICYCLIC ARYL SPHINGOSINE 1-PHOSPHATE ANALOGS

Compounds that have agonist activity at one or more of the S1P receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at S1P receptors. 1106-. (canceled)108. The method of claim 107 , wherein Tis —C(O)(OR) claim 107 , —C(O)N(R)S(OR) claim 107 , —O—P(O)(OR)OR claim 107 , —P(O)(OR) claim 107 , tetrazolyl or —S(O)OR.109. The method of claim 107 , wherein Rand Rare both hydrogen claim 107 , and Ris fluoro claim 107 , chloro claim 107 , bromo claim 107 , iodo claim 107 , methyl claim 107 , trifluoromethyl claim 107 , ethyl claim 107 , propyl claim 107 , isopropyl claim 107 , n-butyl claim 107 , i-butyl claim 107 , t-butyl claim 107 , n-pentyl claim 107 , isopentyl claim 107 , 1 claim 107 ,1-dimethylpropyl claim 107 , neopentyl claim 107 , cyclopentyl claim 107 , n-hexyl claim 107 , cyclohexyl claim 107 , methoxy claim 107 , trifluoromethoxy claim 107 , ethoxy claim 107 , n-propoxy claim 107 , i-propoxy claim 107 , n-butoxy claim 107 , i-butoxy claim 107 , t-butoxy claim 107 , n-pentyloxy claim 107 , i-pentyloxy claim 107 , 1 claim 107 ,1-dimethylpropoxy claim 107 , neopentyloxy claim 107 , cyclopentyloxy claim 107 , n-hexyloxy claim 107 , or cyclohexyloxy.112. The method of claim 107 , further comprising administering to said mammal an effective amount of one or more drugs selected from the group consisting of: a corticosteroid claim 107 , a bronchodilator claim 107 , an antiasthmatic claim 107 , an antiinflammatory claim 107 , an antirheumatic claim 107 , an immunosuppressant claim 107 , an antimetabolite claim 107 , an immunomodulator claim 107 , an antipsoriatic claim 107 , and an antidiabetic.114. The method of claim 113 , wherein Tis —C(O)(OR) claim 113 , —C(O)N(R)S(OR) claim 113 , —O—P(O)(OR)OR claim 113 , —P(O)(OR) claim 113 , tetrazolyl or —S(O)OR.115. The method of claim 113 , wherein Rand Rare both hydrogen claim 113 , and Ris fluoro claim 113 , chloro claim 113 , bromo claim 113 , iodo claim 113 , ...

BENEFITS OF SUPPLEMENTATION WITH N-ACETYLCYSTEINE AND GLYCINE TO IMPROVE GLUTATHIONE LEVELS

Compositions and methods are related to utilizing glycine and N-acetylcysteine for a variety of medical conditions related to reduced levels of glycine, N-acetylcysteine, and/or glutathione, for example, muscle loss such as sarcopenia, HIV infection and other infections, organ damage such as those from diabetes and insulin resistance and diabetic nephropathy, cardiac function and failure such as preventing or improving heart failure, fatty liver, cancer prevention, and other conditions. 112-. (canceled)13: A method of neutralizing or mitigating a drug-induced mitochondrial dysfunction or impairment for an individual , the method comprising providing to the individual an effective amount of a composition comprising glycine or a functional derivative thereof and N-acetylcysteine or a functional derivative thereof , wherein the drug-induced mitochondrial dysfunction or impairment is from at least one drug consumed by the individual selected from the group consisting of an anticonvulsant; a psychotropic other than an antipsychotic drug; an analgesic/anti-inflammatory drug other than acetaminophen; an antibiotic; an anti-arrhythmic drug; a steroid; a beta-blocker; and an immunization.14: The method of claim 13 , wherein the drug is selected from the group consisting of Valproate; Amitriptyline; Amoxapine; Fluoxetine; Citalopram; Phenobarbital; Secobarbital; Butalbital; Ambarbital; Pentobarbital; Alprazolam; Diazepham; Statins; Bile acids-cholestryamine; Ciprofibrate; Acetylsalicylic Acid; Indomethacin; Naproxen; Diclofenac; Tetracycline claim 13 , minocycline; Chloramphenicol; Aminoglycosides; Linozolid; Amiodarone; Doxorubicine; Cis-platinum; Tamoxifen; Metformin; and a mixture thereof.15: The method of claim 13 , wherein the psychotropic drug comprises at least one of an Antidepressant; Barbiturate; or Anxiety medication.16: A method of treating an individual for a medical condition or physical state claim 13 , the method comprising providing to the individual an ...

METHODS FOR TREATING CANCER USING INOS-INHIBITORY COMPOSITIONS

Disclosed are methods for treating one or more mammalian cancers, and in particular, methods for treating human melanoma, or a head or neck cancer, that employ therapeutically-effective amounts of one or more iNOS pathway-inhibitory compounds, either alone, or in combination with one or more selected antihypertensive agents (including, for example, calcium channel antagonists), alone, or further in combination with one or more conventional chemotherapeutic agents. Also disclosed are pharmaceutical formulations that comprise these compositions, as well as methods for their use in treating refractory, metastatic, and/or relapsed cancers, or, for use in the management or reversal of treatment resistance in one or more such mammalian cancers. 2. The method of claim 1 , wherein the melanoma or the head/neck cancer is identified as a refractory or a relapsed form of the disease.3. The method of claim 1 , wherein the melanoma or the head/neck cancer is characterized as treatment-resistant claim 1 , radioresistant claim 1 , metastatic claim 1 , or any combination thereof.4. The method of claim 1 , wherein the first iNOS inhibitor comprises N-monomethyl-L-arginine [L-NMMA] claim 1 , (N-[[3-(aminomethyl)phenyl] methyl]-ethanimidamide) [1400 W] claim 1 , or (N-[imino(nitroamino) methyl]-L-ornithine methyl ester) [L-NAME].5. The method of claim 4 , wherein the first iNOS inhibitor comprises N-monomethyl-L-arginine [L-NMMA].6. The method of claim 1 , wherein the first antihypertensive agent comprises a first calcium channel antagonist.7. The method of claim 6 , wherein the first calcium channel antagonist is selected from the group consisting of amlodipine claim 6 , aranidipine claim 6 , azelnidipine claim 6 , barnidipine claim 6 , benidipine claim 6 , clinidipine claim 6 , clevidipine claim 6 , diltiazem claim 6 , efonidipine claim 6 , fendiline claim 6 , felodipine claim 6 , gallopamil claim 6 , isradipine claim 6 , lacidipine claim 6 , lercanidipine claim 6 , manidipine claim ...

BICYCLIC ARYL SPHINGOSINE 1-PHOSPHATE ANALOGS

Compounds that have agonist activity at one or more of the S1P receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at S1P receptors. 131-. (canceled)33. The method of claim 32 , wherein Tis —C(O)(OR) claim 32 , —C(O)N(R)S(OR) claim 32 , —O—P(O)(OR)OR claim 32 , —P(O)(OR) claim 32 , tetrazolyl or —S(O)OR.34. The method of claim 32 , wherein Rand Rare both hydrogen claim 32 , and Ris fluoro claim 32 , chloro claim 32 , bromo claim 32 , iodo claim 32 , methyl claim 32 , trifluromethyl claim 32 , ethyl claim 32 , propyl claim 32 , isopropyl claim 32 , n-butyl claim 32 , i-butyl claim 32 , t-butyl claim 32 , n-pentyl claim 32 , isopentyl claim 32 , 1 claim 32 ,1-dimethylpropyl claim 32 , neopentyl claim 32 , cyclopentyl claim 32 , n-hexyl claim 32 , cyclohexyl claim 32 , methoxy claim 32 , trifluoromethoxy claim 32 , ethoxy claim 32 , n-propoxy claim 32 , i-propoxy claim 32 , n-butoxy claim 32 , i-butoxy claim 32 , t-butoxy claim 32 , n-pentyloxy claim 32 , i-pentyloxy claim 32 , 1 claim 32 ,1-dimethylpropoxy claim 32 , neopentyloxy claim 32 , cyclopentyloxy claim 32 , n-hexyloxy claim 32 , or cyclohexyloxy.37. The method of claim 36 , wherein Tis —C(O)(OR) claim 36 , —C(O)N(R)S(OR) claim 36 , —O—P(O)(OR)OR claim 36 , —P(O)(OR) claim 36 , tetrazolyl or —S(O)OR.38. The method of claim 36 , wherein Rand Rare both hydrogen claim 36 , and Ris fluoro claim 36 , chloro claim 36 , bromo claim 36 , iodo claim 36 , methyl claim 36 , trifluromethyl claim 36 , ethyl claim 36 , propyl claim 36 , isopropyl claim 36 , n-butyl claim 36 , i-butyl claim 36 , t-butyl claim 36 , n-pentyl claim 36 , isopentyl claim 36 , 1 claim 36 ,1-dimethylpropyl claim 36 , neopentyl claim 36 , cyclopentyl claim 36 , n-hexyl claim 36 , cyclohexyl claim 36 , methoxy claim 36 , trifluoromethoxy claim 36 , ethoxy claim 36 , n-propoxy claim 36 , i-propoxy claim 36 , n-butoxy claim 36 , i-butoxy claim 36 , t-butoxy claim 36 , n-pentyloxy claim 36 , ...

Crystalline salts of 5-methyl-(6S)-tetrahydrofolic acid and L-valine ethyl ester

The present invention refers to a crystalline salt comprising 5-methyl-(6S)-tetrahydrofolic acid and L-valine ethyl ester wherein the molar ratio of 5-methyl-(6S)-tetrahydrofolic acid and L-valine ethyl ester is from to (in mol/mol) and/or hydrates and/or solvates thereof as well as to a process of obtaining the same. 1. A crystalline salt comprising 5-methyl-(6S)-tetrahydrofolic acid and L-valine ethyl ester wherein the molar ratio of 5-methyl-(6S)-tetrahydrofolic acid to L-valine ethyl ester is from 1:0.3 to 1:3.0 (in mol/mol) and/or hydrates and/or solvates thereof.2. The crystalline salt of claim 1 , wherein the molar ratio of 5-methyl-(6S)-tetrahydrofolic acid to L-valine ethyl ester is from 1:0.5 to 1:2.5 (in mol/mol) and/or hydrates and/or solvates thereof.3. The crystalline salt of claim 1 , wherein the molar ratio of 5-methyl-(6S)-tetrahydrofolic acid to L-valine ethyl ester is from 1:0.75 to 1:1.25 (in mol/mol) and/or hydrates and/or solvates thereof.4. The crystalline salt of claim 1 , wherein the ratio of 5-methyl-(6S)-tetrahydrofolic acid L-valine ethyl ester is approximately 1:1 (in mol/mol) and/or hydrates and/or solvates thereof.5. The crystalline salt of claim 1 , characterized in that the salt is the salt of 5-methyl-(6S)-tetrahydrofolic acid and L-valine ethyl ester and has a PXRD pattern with at least one characteristic peak (expressed in 2θ±0.2° 2θ (CuKα radiation)) selected from the following peaks located at 5.8 claim 1 , 6.9 claim 1 , 14.0 claim 1 , 19.0 claim 1 , 19.3 claim 1 , 22.2 and 25.9 (Form A).6. The crystalline salt of claim 1 , characterized in that the salt is the salt of 5-methyl-(6S)-tetrahydrofolic acid and L-leucine ethyl ester and has a PXRD pattern with characteristic peaks (expressed in 2θ±0.2° 2θ (CuKα radiation)) at 5.8 claim 1 , 6.9 claim 1 , 14.0 claim 1 , 19.0 claim 1 , 19.3 claim 1 , 22.2 and 25.9 (Form A).7. The crystalline salt of claim 1 , characterized in that the salt is the salt of 5-methyl-(6S)-tetrahydrofolic ...

METHOD FOR TREATING INTESTINAL FIBROSIS

A method for treating intestinal fibrosis in a subject, comprising enterally administering a steroid to the subject. The steroid may be in a multiple minibead formulation. 1. An oral steroid formulation , the formulation being a multiple minibead formulation wherein the minibeads comprise a water-soluble polymer matrix in which a steroid is distributed , wherein the steroid is distributed in the polymer matrix in any of the following forms:a) as a solution in the polymer matrix;b) dissolved in a disperse phase;c) as particles dispersed in a disperse phase;d) dissolved in the aqueous phase of a water-in-oil or water-in-wax emulsion dispersed in the polymer matrix.2. The formulation according to claim 1 , wherein the steroid is a steroid susceptible to first pass metabolism.3. The formulation according to claim 2 , wherein the steroid susceptible to first pass metabolism is selected from budesonide claim 2 , flunisolide claim 2 , fluticasone proprionate claim 2 , rimexolone claim 2 , butixocort claim 2 , tixocortol and beclomethasone and the salts and esters claim 2 , thereof.4. The formulation according to wherein the steroid is budesonide claim 2 , or an ester thereof.5. The formulation according to claim 1 , wherein the steroid is dissolved in a disperse phase.6. The formulation according to claim 1 , wherein the composition comprises a dispersed phase distributed within the matrix.7. The formulation according to claim 6 , wherein the dispersed phase comprises an oil.8. The formulation according to claim 5 , wherein the dispersed phase comprises olive oil claim 5 , sesame oil claim 5 , coconut oil claim 5 , palm kernel oil claim 5 , medium chain triglycerides claim 5 , linoleoyl macrogolglycerides (polyoxylglycerides) claim 5 , caprylocaproyl macrogolglycerides and caprylic/capric triglycerides claim 5 , 2-(2-ethoxyethoxy)ethanol claim 5 , poly(ethylene glycol) or a combination thereof.9. The formulation according to claim 5 , wherein the dispersed phase comprises ...

SYNERGISTIC ANTIBACTERIAL EFFECTS OF MAGNOLIA BARK EXTRACT AND L-ARGININE, N-ALPHA-LAUROYL ETHYL ESTER ON PLAQUE BIOFILM

The present disclosure relates generally to oral compositions and methods for inhibiting the formation of plaque biofilm by salivary bacteria, and more particularly, to oral compositions comprising a combination of magnolia bark extract (MBE) and L-arginine, N-lauroyl ethyl ester (LAE). The oral compositions are useful for improving oral health, including inhibiting the formation of plaque biofilm by salivary bacteria and reducing plaque adherence to teeth. 1. An oral composition for inhibiting the formation of plaque biofilm by salivary bacteria in an oral cavity of a consumer , the composition comprising magnolia bark extract (MBE) and L-arginine , N-lauroyl-ethyl ester (LAE) , wherein the oral composition comprises the MBE and LAE in amounts that provide a synergistic inhibition of the formation of plaque biofilm in the oral cavity.2. The oral composition of claim 1 , wherein the weight ratio of MBE to LAE is from about 16:1 to about 4:1.3. The oral composition of or claim 1 , wherein the weight ratio of MBE to LAE is from about 16:1 to about 8:1.4. The oral composition of or claim 1 , wherein the weight ratio of MBE to LAE is from about 8:1 to about 4:1.5. The oral composition of any one of the preceding claims claim 1 , wherein the oral composition comprises from about 1 to about 20 mg of MBE.6. The oral composition of any one of the preceding claims claim 1 , wherein the oral composition comprises from about 1 to about 10 mg of MBE.7. The oral composition of any one of the preceding claims claim 1 , wherein the oral composition comprises from about 1 to about 20 mg of LAE.8. The oral composition of any one of the preceding claims claim 1 , wherein the oral composition is selected from the group consisting of a chewing gum claim 1 , a confection claim 1 , a mint claim 1 , a tablet claim 1 , a bead claim 1 , and a lozenge.9. The oral composition of claim 8 , wherein the oral composition is a chewing gum claim 8 , and the synergistic inhibition of the formation ...

HEPATITIS B ANTIVIRAL AGENTS

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: 11. A pharmaceutical composition claim 1 , comprising a compound or a combination of compounds according to claim 1 , in combination with a pharmaceutically acceptable carrier or excipient.12. A method of treating or preventing an HBV infection in a subject in need thereof claim 1 , comprising administering to the subject a therapeutically effective amount of a compound or a combination of compounds according to .13. The method of claim 12 , further comprising administering to the subject at least one additional therapeutic agent selected from the group consisting of HBV polymerase inhibitors claim 12 , interferon claim 12 , viral entry inhibitors claim 12 , viral maturation inhibitors claim 12 , capsid assembly or core protein inhibitors or modulators claim 12 , reverse transcriptase inhibitors claim 12 , TLR-agonists claim 12 , inducers of cellular viral RNA sensor claim 12 , therapeutic vaccines claim 12 , RNA interence (RNAi) or small interfering RNA (siRNA) and combinations thereof.14. The method of claim 13 , wherein the compound and the at least one additional therapeutic agent are co-formulated.15. The method of claim 13 , wherein the at least one additional therapeutic agent is administered at a lower dose and/or frequency than that which is therapeutically effective when said agent is administered alone. This application claims the benefit of U.S. Provisional Application No. 62/304,671, filed on Mar. 7, 2016, and 62/337,675, filed on May 17, 2016. The entire teachings of the above applications are incorporated herein by reference.The present invention relates generally to novel antiviral agents. Specifically, the present invention relates to compounds which can inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle, compositions comprising such compounds, methods for inhibiting ...

Compositions and methods for enhancing brain function

A nutritional supplement composition enhances cognitive function and includes huperzine A, vinpocetine, acetyl-L-carnitine, and rhodiola. The composition is formulated for oral administration. The huperzine A, vinpocetine, acetyl-L-carnitine, and rhodiola are in a ratio a:b:c:d: respectively such that a as the huperzine A is between about 0.8 and 1.2, b as vinpocetine is between about 80 and 120, c as rhodiola is about 1,600 and 2,400, and d as the acetyl-L-carnitine is between about 8,000 and 12,000.

COMPOSITIONS AND METHODS FOR TREATMENT OF RETINAL DEGENERATIVE DISEASES

This disclosure relates to compositions for use in treatment of Alzheimer's Disease, and/or a ocular and retinal degenerative disease, such as age related macular degeneration. The described compositions include effective amounts of LLMe, the hydrobromide form thereof, or functional derivatives thereof. Methods of treatment of a retinal degenerative disease of Alzheimer's Disease using the described compositions are also provided.

Drug composition for parenteral administration

Provided is a curcumin pharmaceutical preparation that is highly water soluble, can maintain the concentration of free curcumin in the blood sufficiently high by being administered parenterally, can effectively obtain a pharmacological action of curcumin, and is highly safe. A pharmaceutical composition for parenteral administration, including a water-soluble substance conjugate of curcumin as an active component.

ASSAYS, METHODS AND MEANS

A novel class of hydroxylases is described having the amino acid sequence of SEQ ID NO: 2, 4, 6 and 8, and variants and fragments thereof having HIF hydroxylation activity. The polypeptides of the invention have in particular prolyl hydroxylase activity. An assay method monitors the interaction of the HIF hydroxylase with a substrate. Modulators of HIF hydroxylase are provided for use in the treatment of a condition associated with increased or decreased HIF levels or activity or for the treatment of a condition where it is desirable to modulate HIF levels or activity. 155-. (canceled)56. A method of treatment of a condition where an increase in HIF levels is desirable by administering to a subject a substance that inhibits the hydroxylation of one or more proline residues of a human HIF-α protein mediated by a HIF prolyl hydroxylase , wherein the HIF prolyl hydroxylase is human EGLN-1 , and wherein the substance is a 2-oxoglutarate analogue that binds to the active site metal iron ion of human EGLN-1 and to Arg383 of human EGLN-1.57. The method of claim 56 , wherein the 2-oxoglutarate analogue has been identified as inhibiting such hydroxylation by means of assays comprising:contacting a HIF prolyl hydroxylase and a substrate of the HIF prolyl hydroxylase under conditions in which the HIF prolyl hydroxylase interacts with the substrate, in the presence or absence of a test substance; anddetermining the interaction, or lack of interaction of, the HIF prolyl hydroxylase and the substrate, and/or by measuring the hydroxylase activity of the HIF prolyl hydroxylase.58. The method of claim 56 , wherein angiogenesis is promoted by the treatment.59. The method of claim 56 , wherein erythropoiesis is promoted by the treatment.60. The method of claim 56 , wherein the condition is a hypoxic condition.61. The method of claim 60 , wherein the hypoxic condition is anaemic claim 60 , histotoxic claim 60 , stagnant or generalized hypoxia.62. The method of claim 61 , wherein the ...

ASSAYS, METHODS AND MEANS

A novel class of hydroxylases is described having the amino acid sequence of SEQ ID NO: 2, 4, 6 and 8, and variants and fragments thereof having HIF hydroxylation activity. The polypeptides of the invention have in particular prolyl hydroxylase activity. An assay method monitors the interaction of the HIF hydroxylase with a substrate. Modulators of HIF hydroxylase are provided for use in the treatment of a condition associated with increased or decreased HIF levels or activity or for the treatment of a condition where it is desirable to modulate HIF levels or activity.

Biologically Active Cannabidiol Analogs

Biologically active cannabidiol analogs comprising a compound of the formula 2. The pharmaceutical composition of claim 1 , wherein the dicarboxylic acid is an organic compound containing two carboxyl functional groups having the formula HOC—R—COH claim 1 , where R is a straight chain or branched aliphatic or aromatic lower alkyl.3. The pharmaceutical composition of claim 1 , wherein the analog is CBD-Di-Alaninate-Di-Hemisuccinate claim 1 , CBD-Divalinate-Di-Hemisuccinate claim 1 , CBD-Mono-Valinate-Mono-Hemisuccinate claim 1 , or CBD-monovalinate-dihemisuccinate.7. The pharmaceutical composition of comprising the biologically active cannabidiol analogs of in a pharmaceutically acceptable carrier.8. The pharmaceutical composition of comprising the biologically active cannabidiol analog of in a pharmaceutically acceptable carrier.9. The pharmaceutical composition of claim 1 , wherein the dicarboxylic acid is malonic acid claim 1 , malic acid claim 1 , glutaric acid claim 1 , succinic acid claim 1 , and phthalic acid.10. The pharmaceutical composition of comprising the biologically active cannabidiol analog of in a pharmaceutically acceptable carrier.11. The pharmaceutical composition for analgesic treatment in combination with a sub-analgesic dose of morphine in cisplatin induced neuropathy comprising the biologically active cannabidiol analogs of in a pharmaceutically acceptable carrier.12. The pharmaceutical composition of claim 11 , wherein the dicarboxylic acid is an organic compound containing two carboxyl functional groups having the formula HOC—R—COH claim 11 , where R is a straight chain or branched aliphatic or aromatic lower alkyl.13. The pharmaceutical composition of claim 11 , wherein the analog is CBD-Di-Alaninate-Di-Hemisuccinate claim 11 , CBD-Divalinate-Di-Hemisuccinate claim 11 , CBD-Mono-Valinate-Mono-Hemisuccinate claim 11 , or CBD-monovalinate-dihemisuccinate.17. The pharmaceutical composition of comprising the biologically active cannabidiol ...

Biologically Active Cannabidiol Analogs

Biologically active cannabidiol analogs comprising a compound of the formula wherein one of R 1 or R 2 or both is/are the residue of a moiety formed by the reaction of an amino group of the amino acid ester of R 1 or R 2 or both with a dicarboxylic acid or a dicarboxylic acid derivative and the other R 1 or R 2 (in the case of the mono) is the residue of a dicarboxylic acid or dicarboxylic acid derivative or Hydrogen (H), (i.e. underivatized), and salts thereof. These CBD analogs are be useful in pain management in oncology and other clinical settings in which neuropathy is presented. Furthermore, these CBD-analogs are useful in blocking the addictive properties of opiates.

Biologically Active Cannabidiol Analogs

Biologically active cannabidiol analogs comprising a compound of the formula 2. The pharmaceutical composition of claim 1 , wherein the dicarboxylic acid is an organic compound containing two carboxyl functional groups having the formula HOC—R—COH claim 1 , where R is a straight chain or branched aliphatic or aromatic lower alkyl.3. The pharmaceutical composition of claim 1 , wherein the analog is CBD-Di-Alaninate-Di-Hemisuccinate claim 1 , CBD-Divalinate-Di-Hemisuccinate claim 1 , CBD-Mono-Valinate-Mono-Hemisuccinate claim 1 , or CBD-monovalinate-dihemisuccinate.7. The pharmaceutical composition of comprising the biologically active cannabidiol analogs of in a pharmaceutically acceptable carrier.8. The pharmaceutical composition of comprising the biologically active cannabidiol analog of in a pharmaceutically acceptable carrier.9. The pharmaceutical composition of claim 1 , wherein the dicarboxylic acid is malonic acid claim 1 , malic acid claim 1 , glutaric acid claim 1 , succinic acid claim 1 , and phthalic acid.10. The pharmaceutical composition of comprising the biologically active cannabidiol analog of in a pharmaceutically acceptable carrier. This application is a Divisional of U.S. application Ser. No. 16/073,766 filed on Jul. 27, 2018, which is a National Stage Entry of International Application No. PCT/US17/15366, filed on Jan. 27, 2017, which claims priority to U.S. Provisional Application No. 62/289,184, filed on Jan. 29, 2016, the disclosures of which are hereby incorporated by specific reference thereto.The present invention is directed to the development of biologically active cannabidiol analogs capable of being formulated into pharmaceutical compositions, and methods of using such compositions for a pharmacological benefit. In a further embodiment of the present invention biologically active CBD analogs possessed analgesic properties alone and in combination of a sub-analgesic dose of morphine in cisplatin induced neuropathy. Furthermore, these ...

METHODS FOR TREATING BREAST CANCER USING INOS-INHIBITORY COMPOSITIONS

Disclosed are methods for treating one or more mammalian cancers, particularly, human breast cancers, including triple-negative breast cancer (TNBC), that employ therapeutically-effective amounts of one or more iNOS pathway-inhibitory compounds, such as L-NMMA, in combination with one or more selected calcium channel antagonists, one or more chemotherapeutic agents, one or more anti-PD-1 antibodies, and one or more doses of ionizing radiation. Also disclosed are pharmaceutical formulations that comprise these compositions, as well as methods for their use in treating refractory, metastatic, and/or relapsed cancers, or, for use in the management or reversal of treatment resistance in one or more types of human breast cancer. 1. A method of treating or ameliorating one or more symptoms of breast cancer in an animal in need thereof , the method comprising administering to the animal a composition comprising:{'sup': 'G', '1) a therapeutically-effective amount of N-monomethyl-L-arginine (L-NMMA); and'}2) a therapeutically-effective amount of amlodipine; and3) a therapeutically-effective amount of a first chemotherapeutic agent;for a time sufficient to treat or ameliorate the one or more symptoms of breast cancer in the animal.2. The method of claim 1 , wherein the breast cancer is identified as a refractory or a relapsed form of the disease.3. The method of claim 1 , wherein the breast cancer is characterized as treatment-resistant claim 1 , radioresistant claim 1 , metastatic claim 1 , or any combination thereof.4. The method of claim 1 , wherein the composition further comprises: 4) one or more of an immunomodulating agent claim 1 , a neuroactive agent claim 1 , an anti-inflammatory agent claim 1 , an anti-lipidemic agent claim 1 , a hormone claim 1 , a receptor agonist claim 1 , a receptor antagonist claim 1 , an anti-infective agent claim 1 , a protein claim 1 , a peptide claim 1 , an antibody claim 1 , an antigen-binding fragment of an antibody claim 1 , an enzyme ...

Novel high penetration drugs and their compositions thereof for treatment of parkinson diseases

One aspect of the invention provides a composition of novel high penetration compositions (HPC) or a high penetration prodrug (HPP) for treatment of Parkinson's disease. The HPCs/HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPCs/HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

Assays, methods and means

A novel class of hydroxylases is described having the amino acid sequence of SEQ ID NO: 2, 4, 6 and 8, and variants and fragments thereof having HIF hydroxylation activity. The polypeptides of the invention have in particular prolyl hydroxylase activity. An assay method monitors the interaction of the HIF hydroxylase with a substrate. Modulators of HIF hydroxylase are provided for use in the treatment of a condition associated with increased or decreased HIF levels or activity or for the treatment of a condition where it is desirable to modulate HIF levels or activity.

SOLID PHARMACEUTICAL DOSAGE FORM FOR RELEASE OF AT LEAST ONE ACTIVE PHARMACEUTICAL INGREDIENT IN THE ORAL CAVITY

Solid pharmaceutical dosage form for the release of at least one Active Pharmaceutical Ingredient (API) in the oral cavity comprising a core coated by at least one film coating. The core comprises at least one API. One or more organoleptically disturbing sensations induced by one or several of the APIs and/or of inactive components of the solid pharmaceutical dosage form is/are reduced by constituents of said film coating. Said constituents comprise at least one film-forming polymer and at least one flavoring agent or at least one sweetener. 126-. (canceled)27. A method of administering a lozenge with a taste masking film coating comprising placing a lozenge into the mouth and keeping the lozenge in the mouth until the lozenge erodes , wherein the lozenge comprises:a. a direct compressed core, wherein the core comprises at least one Active Pharmaceutical Ingredient (API) and at least one additional component, wherein the core weighs from about 50 mg to about 2000 mg, wherein the at least one API is selected from the group consisting of anesthetics, anti-inflammatory drugs, mucolytics, expectorants and cough suppressants, andb. at least one taste masking film coating, wherein the at least one taste masking film coating comprises at least one film-forming polymer, at least one plasticizer, at least one surfactant, at least one flavoring agent and at least one sweetener, andwherein the solid pharmaceutical dosage form does not contain nicotine,wherein upon administration, the at least one API is capable of being completely dissolved in the oral cavity,wherein the lozenge releases the at least one API within 30 minutes upon administration to the oral cavity from the moment of administration; andwherein the one or more organoleptically disturbing sensations induced by one or more of the at least one API is/are reduced by the taste masking film coating for the duration of the release of the at least one API from the lozenge.28. The method of administering a lozenge ...

METHODS FOR TREATING FIBROMYALGIA SYNDROME

The invention is directed to a method of treating fibromyalgia syndrome in a subject, comprising administering a therapeutically effective amount of a carbamoyl compound, or pharmaceutically acceptable salt thereof. 117-. (canceled)19. The method of claim 18 , wherein the compound having structural Formula (1) is an enantiomer substantially free of other enantiomers or an enantiomeric mixture wherein one enantiomer of the compound having structural Formula (1) predominates.20. The method of claim 19 , wherein one enantiomer predominates to the extent of about 90% or greater.21. The method of claim 20 , wherein one enantiomer predominates to the extent of about 98% or greater.23. The method of claim 22 , wherein one enantiomer predominates to the extent of about 90% or greater.24. The method of claim 23 , wherein one enantiomer predominates to the extent of about 98% or greater.26. The method of claim 25 , wherein one enantiomer predominates to the extent of about 90% or greater.27. The method of claim 26 , wherein one enantiomer predominates to claim 26 , the extent of about 98% or greater.28. The method of claim 25 , wherein the enantiomer is (R)-(beta-amino-benzenepropyl)carbamate.29. The method of claim 28 , wherein the enantiomer of (R)-(beta-amino-benzenepropyl)carbamate predominates to the extent of about 90% or greater.30. The method of claim 29 , wherein the enantiomer of (R)-(beta-amino-benzenepropyl)carbamate predominates to the extent of about 98% or greater. The present invention relates a method of treating fibromyalgia syndrome. More specifically, the present invention is directed to a method of using a carbamate compound alone or in combination with other medications, for the treatment of fibromyalgia syndrome.Fibromyalgia syndrome is a chronic disease involving widespread pain, stiffness and tenderness in musculoskeletal-related tissues including muscles, tendons and ligaments (Bennett, 2009). Patients with fibromyalgia show sleep disturbances, ...

ACTIVE INGREDIENTS STIMULATING TYPE 2 AND/OR TYPE 3 HUMAN BETA-DEFENSINS AND COSMETIC OR PHARMACEUTICAL COMPOSITIONS CONTAINING SUCH ACTIVE INGREDIENTS

The invention relates to active ingredients capable of stimulating direct or indirect expression of type 2 human beta-defensins and/or type 3 human beta-defensins. The invention thus provides an active ingredient capable of stimulating direct or indirect expression of type 2 human beta-defensins and/or type 3 human beta-defensins, characterized in that the active ingredient does not cause any inflammatory, irritation or intolerance reactions. The invention also provides a screening method for the selection of such active ingredients. The invention is applicable to the preparation of cosmetic or pharmaceutical compositions containing such active ingredients. 1. (canceled)2. A method of exerting a bactericidal and/or fungicidal effect on a tissue , said method comprising topically applying on a tissue of a subject in need thereof a cosmetic composition comprising between 0.1% and 1% (w/w) of an aqueous boldo extract obtained by extraction in water and at least one cosmetically acceptable excipient , wherein said cosmetic composition is applied in an amount effective to exert a bactericidal and/or fungicidal effect on the tissue and to stimulate expression of human beta-defensin 2 (hBD2) and/or human beta-defensin 3 (hBD3) in the tissue.3. The method of claim 2 , wherein the amount of the cosmetic composition applied does not act to stimulate inflammatory claim 2 , irritation claim 2 , or intolerance reactions in the tissue.4. The method of claim 2 , wherein the tissue is skin claim 2 , hair claim 2 , nails claim 2 , and/or scalp.5. The method of claim 2 , wherein the tissue is inflicted by a disorder selected from the group consisting of dandruff claim 2 , acne claim 2 , vitiligo claim 2 , bacterial dermatosis claim 2 , and fungicidal dermatosis.6. The method of claim 2 , wherein said cosmetic composition further comprises at least one microbiocidal and/or microbio static agent.7. The method of claim 2 , wherein said cosmetic composition comprises 0.1% (w/w) of the ...

COMPOUNDS AND METHODS FOR DELIVERY OF PROSTACYCLIN ANALOGS

This invention pertains generally to prostacyclin formulations and methods for their use in promoting vasodilation, inhibiting platelet aggregation and thrombus formation, stimulating thrombolysis, inhibiting cell proliferation (including vascular remodeling), providing cytoprotection, preventing atherogenesis and inducing angiogenesis. 2. The compound of claim 1 , wherein Ris selected from the group consisting of phosphate and groups in which ORforms an ester of an amino acid or a protein.3. The compound of claim 1 , wherein ORforms an ester of an amino acid or a protein.4. The compound of claim 1 , wherein ORforms an ester of an amino acid or a dipeptide.5. The compound of claim 1 , wherein ORforms an ester of an amino acid.6. The compound of claim 1 , wherein ORforms an ester of an L-isomer of an amino acid.7. The compound of claim 1 , wherein ORforms an ester of a D-isomer of an amino acid.8. The compound of claim 1 , wherein ORforms an ester of an amino acid selected from the group consisting of proline claim 1 , alanine claim 1 , arginine claim 1 , asparagine claim 1 , aspartic acid claim 1 , cysteine claim 1 , glutamine claim 1 , glutamic acid claim 1 , glycine claim 1 , isoleucine claim 1 , leucine claim 1 , lysine claim 1 , methionine claim 1 , phenylalanine claim 1 , serine claim 1 , threonine claim 1 , valine claim 1 , histidine claim 1 , tryptophan claim 1 , and tyrosine.9. The compound of claim 1 , wherein ORforms an ester of an L-isomer of an amino acid selected from the group consisting of proline claim 1 , alanine claim 1 , arginine claim 1 , asparagine claim 1 , aspartic acid claim 1 , cysteine claim 1 , glutamine claim 1 , glutamic acid claim 1 , glycine claim 1 , isoleucine claim 1 , leucine claim 1 , lysine claim 1 , methionine claim 1 , phenylalanine claim 1 , serine claim 1 , threonine claim 1 , valine claim 1 , histidine claim 1 , tryptophan claim 1 , and tyrosine.10. The compound of claim 1 , wherein ORforms an ester of an amino acid selected ...

PHARMACEUTICAL COMPOSITION COMPRISING (1R,4R)-6'-FLUORO-N,N-DIMETHYL-4-PHENYL-4',9'-DIHYDRO-3'H-SPIRO [CYCLOHEXANE-1,1'-PYRANO-[3,4,B]INDOL]-4-AMINE AND PARACETAMOL OR PROPACETAMOL

The invention relates to a pharmaceutical composition comprising a first pharmacologically active ingredient selected from (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine and the physiologically acceptable salts thereof, and a second pharmacologically active ingredient selected from paracetamol and propacetamol. 1. A pharmaceutical composition comprising:(a) a first pharmacologically active ingredient selected from (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine and the physiologically acceptable salts thereof, and(b) a second pharmacologically active ingredient selected from paracetamol and propacetamol.2. The pharmaceutical composition according to claim 1 , wherein the first pharmacologically active ingredient is (1r claim 1 ,4r)-6′-fluoro-N claim 1 ,N-dimethyl-4-phenyl-4′ claim 1 ,9′-dihydro-3′H-spiro[cyclohexane-1 claim 1 ,1′-pyrano[3 claim 1 ,4 claim 1 ,b]indol]-4-amine in form of the hydrochloride claim 1 , hemicitrate or maleate salt.3. The pharmaceutical composition according to or claim 1 , wherein the second pharmacologically active ingredient is paracetamol.4. The pharmaceutical composition according to any of the preceding claims claim 1 , which contains the first and the second pharmacologically active ingredient in such a weight ratio that they will exert a synergistic therapeutic effect upon administration to a patient.5. The pharmaceutical composition according to any of the preceding claims claim 1 , wherein the relative weight ratio of the first pharmacologically active ingredient to the second pharmacologically active ingredient is within the range of from 1:30 to 1:1 claim 1 ,000 claim 1 ,000.6. The pharmaceutical composition according to any of the preceding claims for use in the prevention or treatment of pain claim 1 , anxiety or epilepsy.7. The pharmaceutical composition according to claim 6 , wherein the pain is: ...