Abstract: Toll-like receptor (TLR) agonists can induce chemokine production. We find that TLR2 and TLR6 are widely expressed on human melanoma cells, and that TLR2/6 agonists (MALP-2 or FSL-1) synergize with interferon-gamma (IFN?) to induce production of CXCL10 from melanoma cells. Furthermore, melanoma cells and immune cells freshly isolated from surgical specimens also respond to TLR2/6 agonists +IFN? by upregulating CXCL10 production, compared to treatment with either agent alone. It is also disclosed herein that these compounds are useful in inducing CLXL10 in other types of cancer. Collectively, these data identify a novel synergy of TLR2/6 agonists +IFN? for inducing CXCL10 production directly from melanoma cells, raising the possibility that intratumoral administration of these agents may improve immune signatures in melanoma and have value in combination with other immune therapies, by supporting T-cell migration into melanoma metastases.

Abstract: To provide a medical device including a substrate and a hydrophilic polymer layer formed on at least a part of the substrate, which satisfies the following conditions (a) to (d): (a) a polymer constituting the hydrophilic polymer layer is a hydrophilic polymer having an acidic group; (b) the hydrophilic polymer layer has a thickness of 1 nm or more and less than 100 nm; (c) a number ratio of basic group/acidic group of the hydrophilic polymer layer is 0.2 or less; and (d) a liquid film retention time at 40 minutes after ultrasonic cleaning in a phosphate buffer solution is 15 seconds or more. The present invention provides a medical device in which a surface of a substrate is hydrophilized, and a method for manufacturing same by a simple method.

Abstract: Described herein are methods of administering the non-steroidal anti-inflammatory drug norketotifen, an isomer, an isomeric mixture, a prodrug, or a pharmaceutically acceptable salt thereof for the treatment of a respiratory disorders such as COPD and asthma to human patient in need of such treatment, without exposing said patient to adverse immune-suppressive effects. Methods include treating acute and potentially life-threatening exacerbations of COPD and asthma with norketotifen.

Abstract: A method of preventing or treating a disease characterized by an excessive immune response in a subject in need thereof is provided. The method includes administering to the subject a composition including an active component, wherein the active component is a first compound, a second compound, a third compound, a pharmaceutically acceptable salt thereof, a solvate thereof, or a combination thereof, wherein the first, second, and third compounds include: respectively.

Abstract: The present invention relates to an aqueous composition comprising a macrolide immunosuppressant drug at a concentration of less than 2% w/v and an amphiphilic carbohydrate compound having a molecular weight in the range 1-50 kDa, for use in treatment of an eye disorder by topical application to the eye, wherein the amphiphilic carbohydrate compound is present at a concentration below 10% w/v of the composition. A preferred carbohydrate compound is quaternary ammonium palmitoyl glycol chitosan (GCPQ). Pharmaceutical compositions and methods of treatment are also provided. The treatment may be for instance dry eye syndromes (DES), vernal keratoconjunctivitis (VKC), eczema, atopic keratoconjunctivitis (AKC), Sjögren syndrome, post-operative refractive surgery, corneal transplant or contact lens intolerance.

Abstract: This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a benzimidazole or imidazopyridine structure which function as inhibitors of DYRK1A protein, and their use as therapeutics for the treatment of Alzheimer's disease, Down syndrome, glioblastoma, autoimmune diseases, inflammatory disorders (e.g., airway inflammation), and other diseases.

Abstract: The present invention relates to methods for treating hypercytokinemia and viral infections associated with hypercytokinemia using a mast cell stabilizing compound, optionally in combination with an antiviral agent. The invention further relates to compositions and dosage forms comprising mast cell stabilizing agents, optionally with an antiviral agent.

Abstract: Disclosed herein are formulations of dexamethasone or a prodrug thereof suitable for delivery by ocular iontophoresis and methods of use thereof.

Abstract: This invention relates to a method for inhibition of skin atrophy, or epithelial or mucosal atrophy in women, or to a method for treatment or prevention of symptoms related to said atrophy, said method comprising administering to the woman an effective amount of the compound of formula (I) or a geometric isomer, a stereoisomer, a pharmaceutically acceptable salt, an ester thereof or a metabolite thereof.

Abstract: Disclosed herein are methods for treatment of estrogen-related medical disorders. The methods of treatment may comprise administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of at least one compound of formula (I) or a pharmaceutically acceptable salt thereof.

Abstract: Described herein are methods of treating a mammal in need of treatment for non-histaminic pruritus by administering to the mammal in need thereof a therapeutically effective amount of RS-norketotifen or a pharmaceutically acceptable salt thereof, thereby reducing the desire to scratch in the mammal. Non-histaminergic types of pruritus are resistant to treatment with selective histamine H-1-, H-2- and H-4-receptor inhibitors. In certain aspects, the non-histaminergic pruritus is associated with diabetes.

Abstract: Described herein are methods of treating a mammal in need of treatment for non-histaminic pruritus by administering to the mammal in need thereof a therapeutically effective amount of RS-norketotifen or a pharmaceutically acceptable salt thereof, thereby reducing the desire to scratch in the mammal. Non-histaminergic types of pruritus are resistant to treatment with selective histamine H-1-, H-2- and H-4-receptor inhibitors. In certain aspects, the non-histaminergic pruritus is associated with a dermal disorder, a psychological disorder, a mental disorder, a nerve disorder, or a systemic disorder.

Abstract: The methods disclosed herein relate to the treatment of histamine H-4-related pruritus associated with nerve disorders, by administering a combined histamine H-1 and H-4 receptor inhibitor, specifically RS-norketotifen or a pharmaceutically acceptable salt thereof. Potentiated antipruritic activity by simultaneous inhibition of histamine H-1 receptors and histamine H-4 receptors are described.

Abstract: The present invention relates to methods of treating neurodegenerative diseases comprising administering, to a subject in need of such treatment, one or more agent that inhibits or reduces the action, including the catalytic activity, of an enzyme of the phospholipase D family, such as phospholipase D1 and/or phospholipase D2. The present invention also relates to cell-based assays which may be used to identify agents that inhibit or reduce the activity of enzymes of the phospholipase D family and that may be used in the treatment of neurodegenerative diseases.

Abstract: The methods disclosed herein relate to the treatment of histamine H-4—related pruritus, by administering a histamine H-4 receptor inverse agonist that selectively accumulates at the biophases of the disorders, specifically RS-norketotifen or a pharmaceutically acceptable salt thereof. Potentiated antipruritic activity by simultaneous inhibition of histamine H-1 receptors and histamine H-4 receptors are described.

Abstract: The present invention relates to an ophthalmological vehicle system for the permeation and/or for the active substance transport of ophthalmological active substances through the cornea and/or the sclera of the eye of mammals. This vehicle system assists the transport of the active substances through the cornea and/or the sclerotic tissue of the eye. The vehicle system is suitable for the prophylaxis and/or treatment of diseases of the front and/or back portion of the eye. Likewise, the present invention relates to an ophthalmological kit, comprising a special ophthalmological composition and also, as separate formulation, an ophthalmological active substance.

Abstract: A method for preventing or treating a disease selected from the group consisting of visceral pain, inflammatory pain, osteoarthritis pain, neuropathic pain, and fibromyalgia in a subject in need thereof, comprising administering to said subject an effective amount of the compound of the following formula (I) or a salt thereof: wherein R1, R2, R3, R4, R5, X and n are as described herein.

Abstract: The present invention is directed to compounds of Formula I: wherein R1, R2, R3, R4, R5, X and n are described herein. These compounds and their pharmaceutically acceptable salts thereof are useful as IK1 channel activators.

Abstract: Ophthalmic compositions containing norketotifen and methods of making the same and the use thereof are disclosed. The methods also comprise administering to the eyes of a mammal in need thereof topical ophthalmic compositions containing norketotifen.

Abstract: Amido compounds are disclosed that have a formula represented by the following: and wherein Cy1, Cy2, n1, n2, R1a, R1b, R2, R3, R4, R5, and R6 are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, inflammatory conditions, autoimmune disorders, cancer, and graft-versus-host disease.

Abstract: 8-Substituted-2,6-methano-3-benzazocines of general structure are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications.

Abstract: The methods disclosed herein relate to the treatment of histamine H-4—related pruritus, by administering a histamine H-4 receptor inverse agonist that selectively accumulates at the biophases of the disorders, specifically RS-norketotifen or a pharmaceutically acceptable salt thereof. Potentiated antipruritic activity by simultaneous inhibition of histamine H-1 receptors and histamine H-4 receptors are described.

Abstract: The present invention relates to methods and compositions for treating a subject suffering from a sclerosing disorder, comprising administering, to the subject, an effective amount of an estrogen receptor antagonist (“ERANT”), wherein said ERANT has essentially no estrogen receptor agonist activity under physiologic conditions.

Abstract: Disclosed herein are methods of diagnosing and treating infectious disease characterized by a pathology that involves hemorrhaging or pathological vascular leakage.

Abstract: The present invention relates to a combination therapy for elevating testosterone levels in male mammals in which an antiestrogen or pharmaceutically acceptable salt thereof is co-administered to the mammal with an additional therapeutic agent selected from an androgen and an aromatase inhibitor. The invention is also directed to a combination therapy for treating males with hypogonadism and disorders related thereto, including reduction of muscle mass. limitation of body performance capacity, reduction of bone density, reduction of libido, reduction of potency, reduction of benign prostatic hyperplasia and infertility.

Abstract: The present invention relates to the long-term administration of a selective estrogen receptor modulator (SERM) with a short half-life for the treatment of a variety of estrogen receptor-mediated conditions. The SERM may be administered at a concentration at or below that of a SERM with a long half-life in order to achieve an equivalent therapeutic effect.

Abstract: The present invention relates to compounds having a pipecolate sulfonamide scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said pipecolate sulfonamide compounds can be used for prophylaxis and/or treatment of psychiatric disorders and neurodegenerative diseases, disorders and conditions.

Abstract: The invention provides novel substituted benzyl piperidine compounds according to Formula (I) as lysophosphatidic acid (LPA) receptor antagonists, their manufacture and use for the treatment of proliferative or inflammatory diseases, such as cancer, fibrosis or arthritis.

Abstract: The present invention discloses compounds according to Formula I: wherein R1, R2, R3, L, and the subscript m are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions, and methods of treatment using the same, for the treatment of cystic fibrosis by administering a compound of the invention.

Abstract: Disclosed is a process for the preparation of drug/carrier inclusion composites which involves co-grinding the mixture of drug and carrier powders in a fluid-jet mill, in particular one using air or nitrogen as the fluid, which is suitably modified to allow mechanical fusion of the powders.

Abstract: The present invention relates to a method of reducing the body weight of a subject by administering an effective amount of an estrogen receptor modulator (ERM), optionally, in combination with an anti-obesity or weight loss agent.

Abstract: Disclosed are novel compounds and a method of treating a disease associated with aberrant leukocyte recruitment and/or activation. The method comprises administering to a subject in need an effective amount of a compound represented by: or physiologically acceptable salt thereof.

Abstract: [Problem] A compound which is useful as an IK1 channel activator is provided. [Means for Solution] As a result of studies on the IK1 channel activator, the present inventors have found that a benzothiophene compound shows effectiveness on visceral pain, inflammatory pain, osteoarthritis pain, neuropathic pain, or fibromyalgia, thereby completing the invention. A compound of the invention has an IK1 channel activation effect, and can also be used as an agent for preventing and/or treating visceral pain, inflammatory pain, osteoarthritis pain, neuropathic pain, or fibromyalgia. In addition, the IK1 channel activator can be used as an agent for preventing and/or treating inflammatory pain, osteoarthritis pain, neuropathic pain, and fibromyalgia.

Abstract: The present invention provides topical ophthalmic formulations comprising a combination of one or more antihistamine agents and optionally one or more vasculature modifying agents such as a ? adrenergic receptor antagonist. Also provided are methods of using the formulations of the invention for treating and/or preventing symptoms associated with migraine headache, and for reducing the frequency, severity and duration of migraine attacks.

Abstract: The present invention relates to ionic silicone hydrogel polymers displaying improved thermal stability. More specifically, the present invention relates to a polymer formed from reactive components comprising at least one silicone component and at least one ionic component comprising at least one anionic group. The polymers of the present invention display good thermal stability and desirable protein uptake.

Abstract: The purpose is to provide a compound which has an intestinal phosphate transporter (NPT-IIb) inhibitory action and is useful as an active ingredient of an agent for treating and/or preventing hyperphosphatemia. A tetrahydrobenzothiophene compound of the following formula (I) has NPT-IIb inhibitory action and can be used as an agent for treating and/or preventing hyperphosphatemia: wherein, R1 represents —O-lower alkyl, -lower alkylene-phenyl, or the like; R2 and R3 are the same as or different from each other and represent H, lower alkyl, cycloalkyl, aryl, heteroaryl or the like, or, R2 and R3 may be combined with a nitrogen atom to which they bind to form 5- to 7-membered saturated cyclic amino; R4's are the same as or different from each other and represent halogen, lower alkyl; and n represents 0 to 2.

Abstract: Compositions, formulations, methods, and systems for treating regional fat deposits comprise contacting a targeted fat deposit with a composition comprising long acting beta-2 adrenergic receptor agonist and a compound that reduces desensitization of the target tissue to the long acting beta-2 adrenergic receptor agonist, for example, glucocorticosteroids and/or ketotifen. Embodiments of the composition are administered, for example, by injection, and/or transdermally.

Abstract: Ophthalmic compositions containing norketotifen and methods of making the same and the use thereof are disclosed. The methods also comprise administering to the eyes of a mammal in need thereof topical ophthalmic compositions containing norketotifen.

Abstract: Methods of the prophylaxis of the development of allergy in a patient at risk of sensitization to an antigen(s) or allergen(s) due to impaired gastrointestinal functions include administering a mast cell inhibitor, e.g., ketotifen, e.g., ketotifen fumarate. Methods for prophylactically treating, reducing, delaying or controlling gastrointestinal disorders include administering a mast cell stabilizer, e.g., ketotifen to a patient in need thereof. Pharmaceutical preparation, composition for use in methods described, are also disclosed. Also disclosed are methods of prophylaxis or treating gastrointestinal and esophageal inflammation, and methods for the prophylaxis of the development of additional allergies to a newly introduced substance in a patient with a preexisting allergy. Such methods include delivery of a mast cell stabilizer, e.g., ketotifen. Oral and topical administration are contemplated within the scope of the methods.

Abstract: Provided are a substituted azole derivative and pharmaceutically acceptable salts thereof, a pharmaceutical composition including an effective amount of the derivative, and a method for treating Parkinson's disease in a mammal including administering an effective amount of the compound to the mammal. The azole derivative of the following Formula (I) and pharmaceutically useful salts thereof have an efficacy against Parkinson's disease from inhibitory effects of the activity of MAO-B.

Abstract: Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula I as follows: wherein Y, R1, R2, R3, R4, RA, and RB are defined herein.

Abstract: Specific Compounds of formula I: or pharmaceutically acceptable salts thereof, wherein m, X, R1, R2, R3, R5, R6 and R7 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

Abstract: The present invention is directed to methods of treating or preventing the development of obesity by administering compounds that stabilize mast cells. In addition, it includes pharmaceutical compositions which have both a mast cell stabilizer and instructions regarding the use of the stabilizer in treating or preventing obesity.

Abstract: The methods disclosed herein relate to the treatment of skin infections in dogs, by administering a therapeutically effective amount of norketotifen. Therapeutic antimicrobial activity of norketotifen against Malassezia sp. is described.

Abstract: Self-preserving ophthalmic formulations containing norketotifen and methods of making the same and the use thereof in patients suffering from xerophthalmia are disclosed. The methods also comprise administering to the eyes of a mammal in need thereof, self-preserving topical ophthalmic formulations containing norketotifen, free from any added preservative.

Abstract: Methods of using a cycloheptathiophene compound for the treatment of xerophthalmia are described, as are formulations and compositions for such treatment.

Abstract: The purpose is to provide a compound which has an intestinal phosphate transporter (NPT-IIb) inhibitory action and is useful as an active ingredient of an agent for treating and/or preventing hyperphosphatemia. A tetrahydrobenzothiophene compound of the following formula (I) has NPT-IIb inhibitory action and can be used as an agent for treating and/or preventing hyperphosphatemia: wherein, R1 represents —O-lower alkyl, -lower alkylene-phenyl, or the like; R2 and R3 are the same as or different from each other and represent H, lower alkyl, cycloalkyl, aryl, heteroaryl or the like, or, R2 and R3 may be combined with a nitrogen atom to which they bind to form 5- to 7-membered saturated cyclic amino; R4's are the same as or different from each other and represent halogen, lower alkyl; and n represents 0 to 2.

Abstract: The invention provides methods of treating autophagy mediated diseases and disorders and related pharmaceutical compositions, diagnostics, screening techniques and kits. In one embodiment, the invention provides a method of determining whether a subject suffers from, or is at risk of developing, and autophagy mediated disease state and/or condition by evaluating LC3 levels.

Abstract: The methods disclosed herein relate to the treatment of atopic inflammatory disorders, such as dermal or pulmonary atopic inflammatory disorders, in humans, by administering a therapeutically effective amount of ractopamine.

Abstract: The invention relates to compounds of structural formula (I): or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein Y, L, X1, X2, Z, R3, R4, and n are defined herein. These compounds are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders.