Abstract: The present invention provides compounds that attenuate the function of the P2X7 receptor for the treatment of human neuropathic pain.

Abstract: Pharmaceutical compositions and dosage forms containing low doses of aripiprazole (Formula (I)) or its derivatives/congeners/analogues (e.g., brexpiprazole or cariprazine), and topiramate (Formula (II)) are provided. A method of treatment and/or prophylaxis of substance-related and/or addictive disorders by administering a combination of aripiprazole, or its congeners/analogues/derivatives (e.g., brexpiprazole or cariprazine), and topiramate is also provided. The aripiprazole is generally administered in immediate release in a daily dose in the range of 1.5 mg to 6 mg, in combination with a controlled release formulation daily dose of topiramate of 23 to 92 mg. Additionally provided is a method of treating a patient wherein a composition containing topiramate and aripiprazole or its derivatives/congeners/analogues is administered for purposes of treatment, and/or prophylaxis of a substance-induced depressive, bipolar or anxiety disorder and other psychiatric conditions.

Abstract: The subject invention pertains to a composition comprising a deubiquitinase inhibitor, including a ubiquitin-specific protease 7-specific inhibitor, and methods of using said composition to treat cancer in subject. The ubiquitin-specific protease 7-specific inhibitor can be HBX 19818 and/or an siRNA, which can inhibit the proliferation of cancerous cells, specifically cancerous cells derived from an HPV infection. The methods can further reduce the growth of cancerous cells in an anchorage-independent manner, reduce cancer cell migration, and reduce cancer cell invasion through the basal membrane.

Abstract: Methods of treating or preventing diseases caused by viral infections via the administration of pyronaridine, quinacrine, and/or tilorone are described. The viral infections can be caused by viruses such as Marburg virus (MARV), Chikungunya virus (CHIKV), norovirus, Middle East Respiratory Syndrome coronavirus (MERS-CoV), and Nipah virus.

Abstract: The invention presented is a remedial opioid overdose mixture that includes a therapeutically effective dose of an opioid receptor antagonist; and, a therapeutically effective dose of an opioid receptor agonist. In one embodiment, the opioid receptor antagonist is naloxone while the opioid receptor agonist is nalbuphine. One specific naxolone derivative is NX-90 and a specific nalbuphine derivative is NB-33. The mixture can be administered intranasally, intravenously and by autoinjector. In some dose mixtures, reversal time is about three minutes.

Abstract: This disclosure relates to administration of a combination of: 1) about 100-110 mg, about 104-106 mg, or about 105 mg of bupropion hydrochloride, or a molar equivalent amount of a free base form or another salt form of bupropion; and 2) about 40-50 mg, about 44-46 mg, or about 45 mg of dextromethorphan hydrobromide, or a molar equivalent amount of a free base form or another salt form of dextromethorphan in certain patient populations, such as patients having moderate renal impairment, patients receiving a concomitant strong CYP2D6 inhibitor, patients who are known CYP2D6 poor metabolizers, those in need of an NMDA antagonist that does not cause dissociation, and those at risk of QT prolongation.

Abstract: Provided is a solution suitable for oral administration of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one(compound (I)) or a salt thereof. A solution for oral administration containing compound (I) or a salt thereof and at least one compound selected from the group consisting of lactic acid, phosphoric acid, glycolic acid, malic acid, tartaric acid, citric acid, succinic acid and acetic acid and having pH 2.5-4.5.

Abstract: A method of treating a subject suffering from an ischemic disease associated with Ca2+ overload is provided, the method including administering to the subject an effective amount of an inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase. Also provided is a method of treating a subject suffering from acute ischemic stroke, the method including administering to the subject an effective amount of the ATR kinase inhibitor berzosertib.

Abstract: Amorphous solid dispersions of nilotinib fumarate or nilotinib tartrate are provided, as well as pharmaceutical compositions thereof, wherein the compositions exhibit enhanced bioavailability in the fasted state. Preferably, the compositions may be orally administered to a patient in either the fed or fasted state, with a decrease or elimination of the food effect. Preferably, following oral administration of the pharmaceutical compositions, there is no substantial difference in the pharmacokinetic parameters (e.g., Cmax, AUC0-t and/or AUC0-infinity) of nilotinib, regardless of whether the pharmaceutical compositions are administered to a subject in the fed or fasted state.

Abstract: The present invention provides a compound of formula IA or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

Abstract: Disclosed is the use of a checkpoint kinase (CHK) inhibitor in combination with i) an immunotherapeutic agent or a therapeutic agent targeting a cancer-promoting/sustaining molecule, and optionally ii) a chemotherapeutic agent such as gemcitabine, in cancer treatment.

Abstract: A pharmaceutical formulation comprising at least one angiotensin type 1 receptor (AT1R) blocker and at least one CXC chemokine receptor 2 (CXCR2) pathway inhibitor.

Abstract: The present disclosure provides a compound external preparation for treating alopecia areata and a preparation method therefor. The compound external preparation includes an active ingredient A and an active ingredient B, the active ingredient A is one or more of a JAK inhibitor and a pharmaceutically acceptable salt thereof, and the active ingredient B is minoxidil or a pharmaceutically acceptable salt thereof. The compound external preparation has good efficacy, good solubility, and good storage stability. The preparation method is simple to operate, and is beneficial to increasing solubility and dissolution rate of the active ingredients, as well as storage stability.

Abstract: Provided herein are methods of treating a skeletal dysplasia such as hypochondroplasia or achondroplasia in a pediatric patient by administering to the patient infigratinib or a pharmaceutically acceptable salt thereof. Also provided are minitablets including infigratinib monophosphate and a pharmaceutically acceptable excipient for use in treating a skeletal dysplasia such as hypochondroplasia or achondroplasia in pediatric patients.

Abstract: Applicant discloses methods for treating a glucocorticoid receptor positive (GR+) neuroepithelial tumor in a subject, comprising administering a selective glucocorticoid receptor modulator (SGRM) in an amount effective to reduce the tumor load in a subject. The GR+ neuroepithelial tumor may be a neurofibromatosis type 2 (NF 2) tumor; the GR+ neuroepithelial tumor may be a schwannoma, meningioma, or ependymoma. In embodiments, the GR+ neuroepithelial tumor is not an adrenocorticotropic hormone (ACTH)-secreting tumor. In embodiments, the SGRM comprises a steroidal backbone. In embodiments, the SGRM is mifepristone. In embodiments, the SGRM comprises a non-steroidal backbone, such as, e.g., a cyclohexyl pyrimidine, a fused azadecalin, a heteroaryl ketone fused azadecalin, or an octahydro fused azadecalin backbone. The SGRM may be administered orally. The SGRM may be administered alone. In embodiments, the SGRM is administered with at least one non-SGRM therapy, e.g.

Abstract: The disclosure provides methods, treatments and materials for treating diseases or disorders mediated by cyclic nucleotides and/or sodium glucose cotransporter 2. In particular, the present disclosure provides for methods of treating such diseases and disorders with a PDE1 inhibitor in combination with additional therapeutic agents.

Abstract: The present disclsoure describes a pharmaceutical combination of an anti-CD19 antibody and a Bruton's tyrosine kinase (BTK) inhibitor and its use for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and/or acute lymphoblastic leukemia.

Abstract: Disclosed herein is a method for the prevention, delay of progression or treatment of indolent or aggressive B-cell lymphomas in an individual in need thereof, comprising administering a Btk inhibitor (in particularly (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo-[1,5-a]pyrimidine-3-carboxamide or a pharmaceutically acceptable salt thereof) in combination with an anti-PD-1 antibody. The potent and selective BTK inhibitor in combination with the anti-PD-1 antibody have a manageable toxicity profile in patients with indolent and aggressive lymphomas.

Abstract: The present invention is directed to pemetrexed formulations comprising a non-aqueous solvent that remains stable after dilution for at least about 48 hours when stored at 2° C. to 8° C. The present invention is also directed to pemetrexed formulations comprising a non-aqueous solvent that remains stable for at least about 24 months when stored at 2° C. to 8° C.

Abstract: The present invention is directed to pemetrexed formulations comprising a non-aqueous solvent that remains stable after dilution for at least about 48 hours when stored at 2° C. to 8° C. The present invention is also directed to pemetrexed formulations comprising a non-aqueous solvent that remains stable for at least about 24 months when stored at 2° C. to 8° C.

Abstract: The invention generally relates to products for use in the treatment and/or prevention of Pulmonary Arterial Hypertension (PAH). More specifically, the invention relates to translocator protein (TSPO) binding members which treat or prevent pulmonary endothelial cell dysfunction, and the use of such TSPO binding members for use in the treatment and/or prevention of PAH [FIG. 1].

Abstract: The disclosure provides, inter alia, methods to treat hypertension in patients using CYP 11?2 beta hydroxylase inhibitors.

Abstract: The present invention relates to a pharmaceutical composition for use in the prevention or treatment of nontuberculous mycobacterium infectious diseases, containing, as an active ingredient, a compound represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof. The compound represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof, according to the present invention, can be used in the prevention or treatment of nontuberculous mycobacterium (NTM) infectious diseases.

Abstract: Provided herein are compositions and methods that improve cognition in individuals having or at risk of having Alzheimers disease, including familial Alzheimers disease, early-onset Alzheimers disease, and middle to late stage Alzheimers disease.

Abstract: Kits, compositions, devices, and methods for administration of olanzapine are provided. Uses thereof to treat nausea and vomiting are also provided.

Abstract: A therapeutic combination of a compound having antiestrogenic activity and a CDK4/6 inhibitor is used in a method for the treatment of BC or other estrogen-responsive tumors in a human patient, wherein the method comprises subjecting the patient to a fasting mimicking diet for a period of 24-190 hours while the patient is being treated with the therapeutic combination, in which the compound having antiestrogenic activity can be a selective estrogen receptor modulator (SERM), a selective estrogen receptor degrader (SERD) or an aromatase inhibitor (AI).

Abstract: Provided herein are steroid containing compositions suitable for providing therapeutically effective amounts of at least one steroid to individuals. Also provided herein are compositions comprising testosterone and/or testosterone derivatives suitable for providing therapeutically effective and safe amounts of testosterone over periods of time. Further provided are methods of treating andro- and/or testosterone deficiency in individuals by administering to the individuals compositions described herein.

Abstract: Compositions and methods for relieving acute pain, muscular pain, neuropathic pain, and the chronic pain by administering an effective amount of an analgesic composition (preferably formulated as a cream, a gel, a lotion, an ointment, or a salve) including at least: (i) one or more cannabis compounds; (ii) histamine dihydrochloride, salicylate, camphor, menthol, primrose oil, capsaicin, or any of the combination thereof; and optionally, four or more compounds acting as at least antimicrobial preservative(s), antioxidant(s), dispersant(s), emollient(s), emulsifier(s), humectant(s), lubricant(s), penetration enhancer(s), skin conditioner(s), skin protectant(s), thickener(s), or any of the combination thereof to an affected area of a subject in need of pain relief. In a preferred embodiment, the optional third category contributes six or more compounds. Relief of acute and chronic pain without significant deleterious side effects is provided thereby.

Abstract: The use of phosphatidylcholines to directly stabilize cannabinoids within dry powder is described. Phosphatidylcholines include 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cannabinoids include tetrahydrocannabinol (THC) and cannabidiol (CBD). The dry powder containing the stabilized cannabinoids can be formulated for inhalation or oral delivery. Dry powder formulated for inhalation can include formyl diketopiperazine (FDKP). Oral delivery of the dry powder containing the stabilized cannabinoids includes delivery to the gastrointestinal tract and to the mucous membranes of the oral cavity.

Abstract: The present disclosure provides formulations comprising a holding medium and homogeneously dispersed therein protein-bound cannabinoid, wherein the cannabinoid and the protein in the protein-bound cannabinoid are at a weight ratio of at least 10 mg cannabinoid to 50 mg protein (10:50 w/w). The formulations have shown to be in the form of particles enabling upon local injection prolonged release of the cannabinoid. Also provided by the present disclosure is a method of obtaining the protein-bound cannabinoid and uses thereof.

Abstract: Provided are methods of treating refractory seizures in a human subject, e.g., a child, that include administering an effective amount of cannabidiol (CBD), e.g., in a transdermal gel.

Abstract: Provided are pharmaceutical compositions for preventing or treating lung cancer, including cannabidiol (CBD) and an anti-cancer agent as active ingredients, and uses thereof, and the compositions have been confirmed to exhibit significantly superior lung cancer inhibitory activity when combination treated with CBD and etoposide, one of the anti-cancer agents for lung cancer, and the compositions can be utilized to enhance the therapeutic effect of lung cancer.

Abstract: A cellular model with a highly glycolytic phenotype (L929dt cells) for study of phosphaplatin-based anticancer agents, in particular (R,R)-1,2-cyclohexanediamine-(pyrophosphato) platinum(II) (or “PT-112”), is disclosed. The expression of HIF-1? as a biomarker of glycolytic cells sensitive to PT-112, clinical applications of the biomarker, and methods thereof for diagnosis and treatment of patients with cancers are disclosed.

Abstract: Provided herein is a leukocyte tyrosine kinase (LTK) inhibitor for use in the treatment of a viral infection in a subject, wherein the viral infection is caused by an RNA virus. Also provided are methods of treating a viral infection in a subject, wherein the viral infection is caused by an RNA virus, the method comprising administering to the subject an LTK inhibitor, and the use of an LTK inhibitor in the manufacture of a medicament for the treatment of a viral infection, wherein the viral infection is caused by an RNA virus. In particular, the infection may be an influenza or coronavirus infection in a human subject.

Abstract: The present invention relates to methods of treatment of infections caused by coronaviridae virus (including COV-ID-19) using ((((((R)-1-(6-amino-9h-purin-9-yl) propan-2-yl) oxy) methyl) (phenoxy) phosphoryl)oxy)methyl pivalate, its derivatives or metabolites thereof. The methods of the present invention can be used in patients with infections caused by coronaviridae virus (including COVID-19) administering ((((((R)-1-(6-amino-9h-purin-9-yl) propan-2-yl) oxy) methyl) (phenoxy) phosphoryl)oxy)methyl pivalate, its derivatives or metabolites in combination with one or more anti-viral drugs.

Abstract: The invention provided herein includes pharmaceutical compositions comprising a TLR7 agonist having the structure of Formula (A), aluminum-containing particles, and one or more pharmaceutically acceptable excipient. The invention further provides the use of such compositions in the treatment of solid tumors either alone or in combination with one or more additional pharmaceutical compositions.

Abstract: A nutritional composition comprising the human milk oligosaccharides (HMOs) 2?-fucosyllactose (2FL), 3?-fucosyl-lactose (3FL), 3?-sialyllactose (3SL), and lacto-N-neotetraose (LNnT). The nutritional composition is useful for treating or preventing disorders associated with an above-normal number of granulocytes in a tissue. For example, the combinations may have utility in preventing or treating eosinophilic gastrointestinal diseases.

Abstract: Disclosed are nutritional compositions including human milk oligosaccharides and nucleotides that can be administered to preterm infants, term infants, toddlers, and children for reducing inflammation and the incidence of inflammatory diseases.

Abstract: The present invention relates to use of a composition comprising an effective amount of a combination of oleuropein and/or metabolite thereof and quercetin and/or derivative for maintenance of joint health or prevention or treatment of joint disorders in an individual. In particular, the invention relates to a composition comprising an effective amount of a combination of oleuropein and/or metabolite thereof and quercetin and/or derivative for use to prevent or treat cartilage degeneration in an individual.

Abstract: Composition comprising a combination of oleuropein or metabolite thereof and nicotinamide riboside thereof are provided. The composition may be an oral nutritional composition, for example a nutritional supplement, an oral nutritional supplement, a food product, a food for special medical purpose (FSMP). The composition can be administered to an individual in need thereof for (i) improving a physiological state or disorder related to NAD deficiency/restriction in one or more cells, (ii) improving a physiological state linked to metabolic fatigue in one or more cells, (iii) increasing mitochondrial energy and mitochondrial calcium uptake in one or more cells, and (iv) increasing antioxidant capacity, reducing oxidative stress and/or enhancing mitochondrial function, (v) treating or preventing a NAD deficiency/depletion disorder in an individual, (vi) improving healthspan.

Abstract: The present disclosure relates to methods for treating viral infections in a patient that is not pregnant. Also provided are combination treatments for viral infections in a human in need thereof.

Abstract: Compositions for prevention or treatment for the SARS family of coronaviruses, e.g., SARS-CoV-2 and SARS-OC43 (common cold virus), include non-nucleoside reverse transcriptase inhibitors (NNRTI), such as rilpivirine, and nucleoside-analogue antiviral agents, such as remdesivir.

Abstract: Disclosed are methods and compositions related to methods of treating, ameliorating, mitigating, slowing, arresting, preventing or reversing various diseases and conditions, including age-related obesity, age-related increases in blood lipid levels, age-related decreases in insulin sensitivity, age-related decreases in memory function, and age-related changes in eye function such as macular degeneration. The methods comprise administering nicotinamide mononucleotide (NMN) to a subject. In some embodiments, the administration can be oral administration. Also disclosed are pharmaceutical compositions comprising NMN.

Abstract: The present disclosure provide for methods of using 6-thio-2?-deoxyguanosine (6-thio-dG) to treat telomerase-positive cancers that exhibit (a) one or more TERT promoter mutations, and/or (b) enriched telomere transcriptional signature(s). In particular, melanomas, including those who are not sensitive or have become resistant to immune checkpoint inhibition and/or MAPKi therapy are targets for this therapy.

Abstract: The present invention provides a nucleic acid having excellent cell membrane permeability.

Abstract: One aspect of the present invention relates to a double stranded iRNA agent comprising an antisense strand which is complementary to a target gene; a sense strand which is complementary to said antisense strand; and one or more lipophilic moieties conjugated to one or more internal positions on at least one strand, optionally via a linker or carrier. Another aspect of the invention relates to a method of gene silencing, comprising administering to a cell or a subject in need thereof a therapeutically effective amount of the lipophilic moieties-conjugated double-stranded iRNAs.

Abstract: Ray tracing hardware accelerators supporting multiple specifiers for controlling the traversal of a ray tracing acceleration data structure are disclosed. For example, traversal efficiency and complex ray tracing effects can be achieved by specifying traversals through such data structures using both programmable ray operations and explicit node masking. The explicit node masking utilizes dedicated fields in the ray and in nodes of the acceleration data structure to control traversals. Ray operations, however, are programmable per ray using opcodes and additional parameters to control traversals. Traversal efficiency is improved by enabling more aggressive culling of parts of the data structure based on the combination of explicit node masking and programmable ray operations. More complex ray tracing effects are enabled by providing for dynamic selection of nodes based on individual ray characteristics.

Abstract: The present invention relates to the administration of heparin or its derivatives, which are anticoagulant, especially low molecular weight heparin (LMWH) in the treatment of especially COVID-19, viral lung diseases, acute and/or chronic lung diseases by means of soft mist inhaler or vibrating mesh technology (VMT) nebulizer through inhalation route. In the present invention, heparin and its derivatives may be administered by means of the passive vibrating mesh nebulizer or active vibrating mesh nebulizer. Anticoagulant heparin or its derivatives reach the lungs efficiently and quickly, and local pulmonary administration is performed such that it provides an effective treatment. Since the drug is targeted directly to the lungs without getting into systemic circulation via local (direct) administration, its concentration is higher at the application region, thereby reducing the side effects and costs per application of the drug, and increasing its efficacy.

Abstract: A PEGylated rapamycin compound and a preparation method therefor and an application thereof. The compound is represented by Formula (I), wherein n is 10-150. The preparation method is as follows: mPEG-COOH is dissolved in an organic solvent, catalysts EDC·HCl and DMAP, and RAPA are added, and the reaction is performed by stirring at 0-40° C. in the dark. An application of the compound and pharmaceutical preparations thereof in the preparation of a drug for reducing immune response can effectively inhibit the production of anti-drug antibodies of biological drugs such as urate oxidase, has good clinical application prospects, and is especially suitable to be prepared into a nano-drug.

Abstract: The present invention relates to zirconium silicate compositions having a lead content that is below 0.6 ppm and methods of manufacturing zirconium silicate at reactor volumes exceeding 200-L with a lead content below 1.1 ppm. The lead content of the zirconium silicate of this invention are within the levels that are considered acceptable for extended use given the dose requirements for zirconium silicate.