Abstract: Provided are applications of disulfiram and derivatives thereof. On the basis of existing protein structure data and small molecule structure data, calculations and analysis are performed using software to screen and obtain compounds capable of effectively interfering with PAICS activity, reducing SAICAR synthesis, and ultimately reducing SAICAR accumulation, in order to achieve the goal of treating or reducing ADSL deficiency. A better effect in the treatment or improvement of ADSL deficiency is expected from the joint use of at least two of the described compounds.

Abstract: The present invention is related to a fixed dose combination tablet formulation comprising the glycosidase inhibitor acarbose (0-4,6-Didesoxy-4-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl] amino}-a-D-glucopyranosyl-(1,4)-0-a-D-glucopyranosyl-(1,4)-D-glucopyranose) and the glycerin-3-phosphate-Dehydrogenase inhibitor metformin (1,1-Dimethylbiguanid), particularly the hydrochloride salt of metformin. Also provided are processes for producing a fixed dose combination tablet formulation.

Abstract: An antiseptic solution comprising a pH-dependent antimicrobial agent, the pH-dependent antimicrobial agent having an operative pH range, wherein the solution has a pH on storage that is lower than the operative pH range. Applicators for applying the antiseptic solution and methods of using the antiseptic solution and applicators are also provided.

Abstract: In this current invention our primary aim to provide a phenylbutyrate conjugates and composition suitable for oral, or parenteral administration which overcomes the abovementioned problems. Phenylbutyrate conjugates are provided, which have a phenylbutyrate moiety covalently linked to a second drug such as Acetaminophen, or other drug molecules which induced hepatotoxicity. A compound for use in the treatment or prevention of a disease selected from hepatotoxicity, drug induced hepatotoxicity, or liver necrosis, and nonalcoholic steatohepatitis (NASH), and treat Pain, fever, cancer, inflammation, a composition for the treatment of ischemic injury or nerve damage in a human or animal, the compound having a structure selected from: **F-I** Formula and Formula **F-II* or anhydride, or pharmaceutically acceptable salt solvate thereof. It is one or more compounds or pharmaceutically acceptable salt or composition comprising a solvate of the foregoing.

Abstract: The disclosure provides for means for a method to facilitate food intake and food retention in a mammal by applying a sufficient dose of a local anesthetic drug in the lumen of the pharyngeal-esophageal-gastric-duodenal tract before or during or after eating. The local anesthetic can be amethocaine, articaine, benzocaine, bupivacaine, chloroprocaine, cinchocaine, cyclomethycaine, dibucaine, diethocaine, etidocaine, larocaine, levobupivacaine, lidocaine, lignocaine, mepivacaine, novocaine, piperocaine, prilocaine, procaine, proparacaine, propoxycaine, QX-222, QX-314, ropivacaine, tetracaine, trimecaine, menthol, eugenol or a safe pharmaceutical formulations of tetrodotoxin, saxitoxin, or neosaxitoxin. The disclosure is useful for patients having problems with food intake or food retention.

Abstract: A method of treating a triterpene-responsive condition, disease or disorder in a subject by administration of an improved triterpene-based composition is provided. An improved triterpene-based composition comprising at least two or at least three triterpenes present at a molar ratio as described herein is also provided.

Abstract: This disclosure relates to deuterated D-?-hydroxybutyric acid (DBHB) of Formula I: wherein each of the variables are defined herein, and pharmaceutically acceptable salts thereof, analogs and prodrugs thereof, pharmaceutical compositions thereof, and methods of use.

Abstract: Pentacyclic triterpene weight loss agents are provided herein. Also provided are pharmaceutical formulations containing a therapeutically effective amount of one or more of the weight loss agents, or pharmaceutically acceptable salts or prodrugs thereof, in combination with one or more pharmaceutically acceptable excipients. The pharmaceutical formulations can be administered to a pre-obese, obese, or morbidly obese patient to induce weight loss, reduce body fat, reduce food intake, improve glucose homeostasis, prevent obesity, or a combination thereof. The weight loss agents can also be co-administered with leptin or a leptin analog.

Abstract: The invention includes a method of preventing or treating acute respiratory distress syndrome (ARDS) in a subject, comprising administering to the subject a thyroid hormone and/or a thyroid receptor ?-agonist.

Abstract: Methods are provided for using 3-OH-kynurenamine to treat and prevent an inflammatory or autoimmune disease or disorder or transplant rejection, and for promoting immune tolerance.

Abstract: Disclosed are hydroquinone compounds, preparation methods therefor, and uses thereof in anti-tumor or immunomodulation. The structural formula of the hydroquinone compounds are shown by formula I, wherein X is C?O or CH2; Y is NH, O or absent; R is: a substituted or unsubstituted alkyl group having at least one carbon atom, a substituted or unsubstituted cycloalkyl group having at least three carbon atoms, a substituted or unsubstituted alkenyl group or alkynyl group having at least two carbon atoms; and a substituted or unsubstituted aryl group or heteroaryl group containing at least four carbon atoms. The compounds provided slowly release 2-tert-butyl-4-methoxyphenol in vivo and maintain stable plasma concentration of 2-tert-butyl-4-methoxyphenol (T1/2=12-24 h). The compounds provided by the present invention protect the phenolic hydroxyl group of 2-tert-butyl-4-methoxyphenol, avoids environmental oxidation and increase the environmental stability of drugs containing the compounds.

Abstract: This invention provides compounds of Formula I wherein B, G, A, E, R1, R3, R4, m and n are as defined herein, which are useful as type I receptor tyrosine kinase inhibitors, and methods of use thereof in the treatment of hyperproliferative disorders in mammals.

Abstract: The current invention is directed to a treatment of a proliferative disease comprising administering to a subject in need of such treatment, a composition comprising epigallocatechin-3-gallate (EGCG), curcumin, glucosinolates and, optionally Daikon radish sprout, alone or in combination with providing a ketogenic diet or a modified ketogenic diet to the subject. The invention also provides a composition comprising medium chain triglycerides, Epigallocatechin-3-gallate, curcumin, compositions comprising glucosinolates and/or derivatives thereof, such as glucoraphanin and its breakdown product sulforaphane, (SFN) (which are found at high levels in broccoli sprouts or sprouts of other cruciferous vegetables), and, optionally Daikon radish sprout.

Abstract: A method of producing a cannabinoid nanoparticle carrier composition for administration to a human, including the steps of incorporating non-ionic surfactants with cannabinoid oils and lipids; inducing sonication for a predetermined period of time at a predetermined amplification with a ultrasonic liquid processor until completely integrated; dissolving ascorbic acid into a carrier fluid; combining in sequence the non-ionic surfactants, lipids, and cannabinoids with a carrier fluid consisting of distilled water and ascorbic acid; sonicating using an ultrasonic liquid processor at predetermined amplitude for a predetermined period of time at a controlled temperature.

Abstract: Methods and formulations for increasing the water solubility and/or bioavailability of a phytocannabinoid compound is disclosed herein. In one example, a water-soluble phytocannabinoid formulation can comprise a phytocannabinoid; a non-ionic surfactant; and optionally, water. The weight ratio of phytocannabinoid content to non-ionic surfactant can be from 1:10,000 to 1:5.

Abstract: Oral compositions provide delivery of cannabinoids to a subject. The oral compare chewable, fast- or slow-dissolving once placed in the mouth of a subject.

Abstract: Provided is a composition for the treatment of diarrheal disease, comprising a polyphenol-rich extract of a mixture of 80-20% by weight of blueberry or bilberry from Vaccinium cyanococcus spp., Vaccinium myrtillis spp., or both; and 20-80% by weight of sloe berry from Prunus spinosa spp. Other compositions, and methods of making and using the compositions for the treatment of diarrheal disease are disclosed.

Abstract: A stable semisolid dosage form (Ointment, Cream or Gel) for ocular delivery of antioxidants, comprising one or more antioxidants as active pharmaceutical ingredient, at least one semisolid base (either Ointment, Gel or a Cream base), and at least one pharmaceutically acceptable excipient, wherein the pH is in the range of about 4 to 8. The present invention provides an emulsion composition that provides release of the active agent in sustained manner. The present invention provides a steady concentration of antioxidants in the aqueous & vitreous humor. The present invention increases the macular pigment optical density (MPOD), for better management of Age Related Macular Degeneration. The present invention provides a semi solid dosage in three different from ointment, cream and gel to treat medical conditions of the eye.

Abstract: Methods and compositions for treating social function disorders are disclosed.

Abstract: The present invention relates to compounds which are effective as catalysts for dismutating superoxide and, more particularly, the manganese or iron complexes of substituted, unsaturated heterocyclic 10-membered macrocyclic complexes that catalytically dismutate superoxide. It also relates to methods of using these complexes to reduce the concentration or the effects of superoxide, pharmaceutical compositions comprising these compounds or their metal complexes, and methods of treating conditions associated with excessive superoxide activity.

Abstract: Disclosed herein is a method of administering to a patient in need thereof a therapeutically effective amount of an extracellular thiol isomerase inhibitor compound to treat or prevent a disease or condition influenced by the activity of one or more extracellular thiol isomerases (e.g. protein disulfide isomerase, ERp5, ERp57, ERp72 and thioredoxin). The disease or condition includes arterial thrombosis, venous thrombosis, a thrombotic disease, a cancer, an infectious disease, a viral disease, an immune disorder, inflammation, a neurologic disease, and a neurodegenerative disorder.

Abstract: The present disclosure provides combination therapy using [(1R)-1-(2-chlorophenyl)-2-(tetrazol-2-yl)ethyl] carbamate (cenobamate) and one or more antiepileptic drugs for the prevention or treatment of a neurological disorder such as epilepsy.

Abstract: Described herein are methods and compositions for the treatment of ocular conditions and for the improvement of vision parameters using pharmaceutically acceptable ophthalmic pilocarpine formulations. A nonlimiting example of an ocular condition that may be treated with the methods and compositions disclosed herein is presbyopia.

Abstract: Stable liquid formulations of bendamustine, and pharmaceutically acceptable salts thereof, and polar aprotic solvents, are described.

Abstract: Provided herein are pharmaceutical formulations of dry-powder bendamustine suitable for pharmaceutical use. Also provided are methods of producing dry-powder bendamustine. The pharmaceutical formulations can be used for any disease that is sensitive to treatment with bendamustine, such as neoplastic diseases.

Abstract: Disclosed herein is a method of treating or preventing motion sickness or at least one symptom thereof, comprising treatment with the NK-1 receptor antagonist, tradipitant.

Abstract: The present invention provides methods for parenterally administering riluzole to subjects in need of treatment.

Abstract: The present invention relates to the use of an Angiotensin II type 1 (AT1) receptor blocker for promoting sleep and/or the treatment of insomnia. It is based, at least in part, on the results of experiments performed using a validated rat model of stress-induced insomnia in which candesartan was found to ameliorate sleep disturbances induced by stress. Further, it was observed that this effect seems to be caused by blockade of AT1 receptors located in several brain regions that are key components of the neural circuitry activated during insomnia. In contrast to currently marketed treatments for insomnia, the AT1 receptor blocker was found to restore normal sleep without inhibiting REM sleep and/or inducing atypical wave components in the EEG.

Abstract: The present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of the formula: wherein R1, R2, R3, R5, R6, R8, M1, M2, M3, M4, M5, M6 and M7 are each independently a member selected from the group consisting of H, C1-6 alkyl, —OH and C1-6 hydroxyalkyl; R4, R7 and R9 are each independently selected from the group consisting of C1-6 alkoxy and OH; R10 is a member selected from the group consisting of H, —OH, —OP(O)Me2, —O—(CH2)n—OH and —O—(CH2)m—O—(CH2)o—CH3, wherein subscripts n and m are each independently from 2 to 8 and subscript o is from 1 to 6; each of L1 and L4 are independently selected from the group consisting of: wherein each M8 is independently a member selected from the group consisting of C1-6 alkyl, OH and C1-6 hydroxyalkyl; each of L2 and L3 are independently selected from the group consisting of: and salts, hydrates, isomers, metabolites, N-oxides and prodrugs thereof.

Abstract: Novel rapamycin analogs and uses thereof are disclosed herein. The rapamycin analogs of the present disclosure show increased mTORC1 specificity and lowered mTORC2 specificity relative to rapamycin.

Abstract: The present invention related to the field of organ transplantation. In one aspect, the present invention provides methods of treating an organ transplant recipient comprising administering to the recipient a therapeutically effective amount of a stem cell mobilizer and an immunosuppressive agent. In particular embodiments, the present invention provides a method of treating an organ transplant recipient comprising administering to the recipient a therapeutically effective amount of an agent that mobilizes CD34+ and/or CD133+ stem cells and a low dose of immunosuppressive agent.

Abstract: The present invention includes substituted chromenones that are useful to inhibit the IRE1/XBP-1 pathway. In certain embodiments, the compounds of the invention inhibit IRE1's RNase activity. In other embodiments, the compounds of the invention are useful to treat or prevent a cancer that involve activation of the ER stress response. The invention also relates, in certain aspects, to the discovery that secretory IgM (sIgM) can orchestrate an immunosuppressive microenvironment by recruiting myeloid-derived suppressor cells (MDSCs) into different tumor models, such as but not limited to solid tumors (such as but not limited to lung cancer) and tumors that have high levels of secreted IgM. In certain embodiments, sIgM produced by B cells or CLL cells can contribute to the accumulation of MDSCs in a tumor. In other embodiments, inhibition of the IRE1/XBP-1 pathway can ablate, minimize, or reduce MDSC levels in a tumor.

Abstract: The present disclosure is directed to novel therapeutic approaches for the prevention, treatment and/or delaying progression of chronic injury, progressive loss of functional parenchymal cells, or fibrosis of an organ. Specifically disclosed are agents for use in increasing homodimer-formation of ARNT in an organ in the prevention, treatment and/or delaying progression of chronic injury, progressive loss of functional parenchymal cells, or fibrosis of said organ, as further defined in the claims. In embodiments, said agent may be (i) an inhibitor of protein phosphatase 2A (PP2A) activity, (ii) an inhibitor of the transcriptional repressor complex FKBP12/YY1, or (iii) an expression construct, which is capable of over-expressing ARNT in said organ, as well as combinations of (i), (ii), and/or (iii).

Abstract: Provided are penicinotam derivatives, a tautomer, a stereoisomer, a racemate, a nonequal mixture of enantiomers, a geometric isomer, a solvate, a pharmaceutically acceptable salt or a prodrug thereof, and a pharmaceutical composition comprising the derivatives. Also provided herein is use of the derivatives and the pharmaceutical compositions in treating diseases caused by inflammation, immune system disorders.

Abstract: The present disclosure is directed to novel compounds of Formula I and pharmaceutically acceptable salts, solvates, solvates of the salt and prodrugs thereof, useful in the prevention (e.g., delaying the onset of or reducing the risk of developing) and treatment (e.g., controlling, alleviating, or slowing the progression of) of cancer, including glioblastoma, bone cancer, head and neck cancer, melanoma, basal cell carcinoma, squamous cell carcinoma, adenocarcinoma, oral cancer, esophageal cancer, gastric cancer, intestinal cancer, colon cancer, bladder cancer, hepatocellular carcinoma, renal cell carcinoma, pancreatic cancer, ovarian cancer, cervical cancer, lung cancer, breast cancer, and prostate cancer. The compounds of the disclosure are selective antagonists of the EP4 receptor and useful treatment of various diseases that may be ameliorated with blockade of PGE2-mediated signaling.

Abstract: The invention relates to the field of tumor treatment, in particular to melanoma tumor treatment. In particular it relates to the use of retinoid X receptor antagonists for use in tumor treatment, in particular for use in reducing tumor cell heterogeneity during minimal residual disease (MRD), and thus for use in treating MRD. Even more in particular, the invention relates to the use of retinoid X receptor antagonists in combination with clinically established treatments such as treatment with a combination of BRAF and MEK inhibitors, and optionally other anticancer agents.

Abstract: Provided are drug delivery compositions and devices useful for the treatment and/or prevention of cancer and metastatic tumors. For example, a drug delivery composition and/or device is provided that comprises a biodegradable scaffold or biomaterial comprising one or more agents that inhibit one or more proinflammatory pathways, such as one or more immune responses mediated by a p38 mitogen-activated protein kinase (MAPK) pathway. In some embodiments, a drug delivery composition and/or device may further comprise one or more agents that activate the innate immune system (e.g., STING agonists) and/or the adaptive immune system (e.g., anti-PD-1 antibodies). In some embodiments, a drug delivery composition and/or device may include a cytokine (e.g., IL-15 superagonist). In some embodiments, a drug delivery composition and/or device can be administered to a tumor resection site (e.g., a void volume resulting from a tumor resection).

Abstract: Compounds represented by Formula (I) or (II): are provided herein, or a pharmaceutically acceptable salt, or a prodrug or bioisostere thereof; wherein R1, R2a, R2b, R2c, R3, R4, R5, R6a, R6b, R2a?, R2b?, R2c?, R3?, R4?, R5?, R6a?, Y, Y?, and the subscripts m and n are as defined herein.

Abstract: Described herein are compounds, pharmaceutical compositions and medicaments that include such compounds, and methods of using such compounds to modulate transient receptor potential vanilloid 1 receptor (TRPV1) activity.

Abstract: A pharmaceutical composition which comprises a therapeutically effective amount of a aminopyridine dispersed in a release matrix, including, for example, a composition that can be formulated into a stable, sustained-release oral dosage formulation, such as a tablet which provides, upon administration to a patient, a therapeutically effective plasma level of the aminopyridine for a period of at about 12 hours and the use of the composition to treat various neurological diseases, including multiple sclerosis. A method of selecting individuals based on responsiveness to a treatment, including, for example, identifying individuals who responded to treatment with a sustained release fampridine composition.

Abstract: This invention relates to a novel method of reducing dermal scars resulting from various types of dermal injuries. Particularly, this invention relates to wound dressings and to scar management products each of which incorporate an active pharmaceutical ingredient to reduce and/or prevent dermal scarring.

Abstract: The present invention provides methods of treatment for cancer(s) through combination therapy with an agent that inhibits poly [ADP-ribose] polymerase (PARP) signaling and an agent that regulates activity within the tumor microenvironment.

Abstract: The present invention relates to the use of cyclin-dependent kinase 9 (CDK9) inhibitors to reduce, inhibit and/or prevent cartilage degradation. CDK9 inhibitors can be used to reduce, inhibit and/or prevent cartilage degradation and loss of cartilage viability during allograft storage. CDK9 inhibitors can be used as a post-injury intervention treatment to reduce, inhibit and/or prevent the acute cellular responses that lead to future cartilage degradation and osteoarthritis.

Abstract: The present invention is directed to piperidinone carboxamide azaindane derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

Abstract: The present disclosure relates generally to compositions and methods of treating neoplastic diseases or cancers, such as glioblastoma and non-Hodgkin's lymphomas, or other cancers in which the subject suffers from an advanced solid tumor, comprising a combination of, or administering a combination of, a bromodomain and extra-terminal protein (BET) inhibitor and at least one chemotherapeutic agent, which does not inhibit BET directly. The BET inhibitor/chemotherapeutic agent combination, or combination therapy, can yield synergistic effects, thereby increasing the effectiveness of the cancer treatment as compared with the administration of either the BET inhibitor or the chemotherapeutic agent alone.

Abstract: The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts thereof: which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: During clinical trials on patients suffering from neurological disorders, it has been observed that some patients obtain dramatic improvements in motor control and/or higher mental functioning, when they receive a combination of dextromethorphan and quinidine, at suitable dosages. Improved motor control has been exemplified to date by improved ability to swallow and/or speak, among victims of stroke, head injury, or ALS. Improved higher mental functioning has been exemplified better job performance, increased ability to analyze and solve problems, and increased ability to have successful and satisfying interactions with other people. These types of effects can be seen in a relatively brief time period, such as within several days to a week.

Abstract: According to the invention, there is provided a solid pharmaceutical composition formulation for nasal delivery of an opioid antagonist, comprising a pharmacologically-effective amount of an opioid antagonist and a pharmaceutically-acceptable carrier. The compositions are preferably in the form of a powder produced by spray-drying, which are subsequently loaded into single use nasal applicators. Preferred pharmaceutically-acceptable carriers in this regard include disaccharides (e.g. lactose or trehalose) and dextrins (e.g. cyclodextrins or maltodextrins), preferably spray-dried together in combination. Compositions may further comprise an alkyl saccharide, preferably a sucrose ester, such as sucrose monolaurate. The compositions and applicators may be employed in the treatment of opioid overdose in subjects.

Abstract: According to the invention, there is provided a solid pharmaceutical composition formulation for nasal delivery of an opioid antagonist, comprising a pharmacologically-effective amount of an opioid antagonist and a pharmaceutically-acceptable carrier. Said compositions are preferably in the form of a powder produced by spray-drying, which are subsequently loaded into single use nasal applicators. Preferred pharmaceutically-acceptable carriers in this regard include disaccharides (e.g. lactose or trehalose) and dextrins (e.g. cyclodextrins or maltodextrins), preferably spray-dried together in combination. Compositions may further comprise an alkyl saccharide, preferably a sucrose ester, such as sucrose monolaurate. Said compositions and applicators may be employed in the treatment of opioid overdose in subjects.

Abstract: There is provided pharmaceutical compositions for the treatment of e.g. opioid dependency comprising microparticles of a pharmacologically-effective amount of buprenorphine, or a pharmaceutically-acceptable salt thereof, in associative admixture with particles comprising a weak acid, or particles comprising weakly-acidic buffer forming materials. The composition may further comprise a disintegrant and/or particles of a pharmacologically-effective amount of naloxone, or a pharmaceutically-acceptable salt thereof. The compositions are useful in the treatment of opioid dependency/addiction and/or pain.