Abstract: The invention relates generally to anti-angiogenesis agents and related methods of using to anti-angiogenesis agents for biomedical applications including direct monotherapy and combination therapy for treatment of an angiogenesis related condition. In an embodiment, the invention provides a class of opioid compounds and structurally related opioid derivatives exhibiting anti-VEGF activity for use in therapeutic procedures, including phototherapy. Opioid compounds and structurally related opioid derivatives of the invention may be administered alone or in combination with administration of a phototherapy agent and/or other therapeutic agent.

Abstract: Selective, non-peptide antagonists of the mu opioid receptor (MOR) and methods of their use are provided. The antagonists may be used, for example, to identify MOR agonists in competitive binding assays, and to treat conditions related to addiction in which MOR is involved, e.g. heroin, prescription drug and alcohol addiction, as well as in the treatment of opioid induced constipation (OIC).

Abstract: Disclosed in certain embodiments is a controlled release oral dosage form comprising a therapeutically effective amount of a drug susceptible to abuse together with one or more pharmaceutically acceptable excipients; the dosage form further including a gelling agent in an effective amount to impart a viscosity unsuitable for administration selected from the group consisting of parenteral and nasal administration to a solubilized mixture formed when the dosage form is crushed and mixed with from about 0.5 to about 10 ml of an aqueous liquid; the dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient.

Abstract: Methods and compositions disclosed herein generally relate to methods of improving clinical and economic outcomes to address adverse effects related to anesthesia, analgesics, opioids, and inadequate pain relief. Embodiments of the invention relate to the association between genes, specific polymorphisms of genes, and non-genetic factors with inadequate pain relief and anesthesia-, analgesic, and/or opioid-related adverse effects. Embodiments of the invention can be used to determine and manage patient risk factors for development of adverse perioperative effects and can allow for personalized anesthesia and pain management for improvement of pain control and reduction of anesthesia-, analgesic-, and opioid-related adverse outcomes. These methods and compositions apply to non-surgical pain management with opioids.

Abstract: An analgesic composition, in parenteral unit dosage form or in a unit dosage form suitable for delivery via the dermis or mucosa, comprises buprenorphine and an amount of naltrexone such that the ratio by weight of buprenorphine to naltrexone delivered to or reaching the plasma of a patient is in the range 100:1 to 5000:1. The analgesic action of the buprenorphine is potentiated by the low dose of naltrexone. Also provided are a method of treatment of pain and the use of buprenorphine and naltrexone for the manufacture of a medicament.

Abstract: The invention relates to a method for identifying compounds that bind and preferably activate a target opioid receptor in a pH-dependent manner.

Abstract: Bivalent ligands that contain two pharmacophores linked through a spacer, one of which interacts with the ?-opioid receptor (MOR) and the other of which interacts with the co-receptor CC chemokine receptor 5 (CCR5), are used for the treatment of neurological disorders such as those associated with AIDS.

Abstract: The invention relates to a pharmaceutical dosage form comprising (i) at least one formed segment (S1), which contains a first pharmacologically active ingredient (A1) and provides prolonged release thereof, and (ii) at least one further segment (S2), which contains a second pharmacologically active ingredient (A2) and provides immediate release thereof, wherein the at least one formed segment (S1) exhibits a higher breaking strength than the at least one further segment (S2) and the at least one formed segment (S1) exhibits a breaking strength of more than 500 N.

Abstract: Disclosed in certain embodiments is a controlled release oral dosage form comprising a therapeutically effective amount of a drug susceptible to abuse together with one or more pharmaceutically acceptable excipients; the dosage form further including a gelling agent in an effective amount to impart a viscosity unsuitable for administration selected from the group consisting of parenteral and nasal administration to a solubilized mixture formed when the dosage form is crushed and mixed with from about 0.5 to about 10 ml of an aqueous liquid; the dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient.

Abstract: The invention relates to a tamper-resistant pharmaceutical dosage form comprising one or more particles, wherein each of said one or more particles comprises a pharmacologically active ingredient and a physiologically acceptable polymer; has a breaking strength of at least 300 N; has a weight of at least 2 mg; and optionally, comprises a film-coating; wherein the total weight of the pharmaceutical dosage form is greater than the total weight of said one or more particles.

Abstract: The invention is directed in part to oral dosage forms comprising a combination of an opioid agonist, acetaminophen and an orally active opioid antagonist, the opioid antagonist being included in a ratio to the opioid agonist to provide a combination product which is analgesically effective when the combination is administered orally, but which is aversive in a physically dependent subject. Preferably, the amount of opioid antagonist included in the combination product provides at least a mildly negative, “aversive” experience in physically dependent addicts (e.g., precipitated abstinence syndrome).

Abstract: Effective methods and compositions to deter abuse of pharmaceutical products (e.g., orally administered pharmaceutical products) including but not limited to immediate release, sustained or extended release and delayed release formulations for drugs subject to abuse comprising at least 10% by weight hydroxypropylcellulose; polyethylene oxide; and a disintegrant selected from the group consisting of crospovidone, sodium starch glycolate and croscarmellose sodium; wherein the ratio of hydroxypropylcellulose to polyethylene oxide on a weight basis is between about 10:1 and 1:10.

Abstract: The use of opioids or opioid mimetics is suggested for the manufacture of a medicament for the treatment of resistant cancer patients.

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: Methods and materials related to the use of morphine, morphine precursors (e.g., reticuline), and inhibitors of morphine synthesis or activity to treat diseases, to reduce inflammation, or to restore normal function are provided.

Abstract: The present invention relates to methods for treating uremic pruritus with anti-pruritic compositions.

Abstract: Disclosed in certain embodiments is an oral dosage form comprising a plurality of particles, each particle comprising a compressed core comprising: (i) an active agent susceptible to abuse and (ii) a gelling agent; wherein the plurality of particles contains a therapeutically or prophylactically effective amount of the active agent; and wherein the viscosity of the dosage form mixed with from about 0.5 to about 10 ml of an aqueous liquid is unsuitable for parenteral or nasal administration.

Abstract: The present invention relates to novel therapeutic and diagnostic dendrimers. In particular, the present invention is directed to dendrimer-linker conjugates, methods of synthesizing the same, compositions comprising the conjugates, as well as systems and methods utilizing the conjugates (e.g., in diagnostic and/or therapeutic settings (e.g., for the delivery of therapeutics, imaging, and/or targeting agents (e.g., in disease (e.g., cancer) diagnosis and/or therapy, pain therapy, etc.)). Accordingly, dendrimer-linker conjugates of the present invention may further comprise one or more components for targeting, imaging, sensing, and/or providing a therapeutic or diagnostic material and/or monitoring response to therapy.

Abstract: There is provided pharmaceutical compositions for the treatment of pain comprising a pharmacologically-effective amount of an opioid analgesic, or a pharmaceutically-acceptable salt thereof, presented in particulate form upon the surfaces of carrier particles comprising a pharmacologically-effective amount of an opioid antagonist, or a pharmaceutically-acceptable salt thereof, which carrier particles are larger in size than the particles of the opioid analgesic. The compositions are also useful in prevention of opioid abuse by addicts.

Abstract: The present invention relates generally to the co-administration of an opioid agonist compound and an analgesic compound. In addition, the invention relates to, among other things, dosage forms for co-administration of an opioid agonist compound and an analgesic compound, methods for administering an opioid agonist compound and an analgesic compound, compositions comprising an opioid agonist compound and an analgesic compound, dosage forms comprising an opioid agonist compound and an analgesic compound, and so on.

Abstract: In some embodiments, the invention provides a non-addictive analgesic co-formulation comprising an opioid agonist in an amount sufficient to confer analgesia in a mammalian subject (such as a human) and a neutral opioid antagonist in an amount sufficient to inhibit peripheral effects of the opioid agonist, and insufficient to block substantial central effects of the opioid agonist in the subject. The formulation may be formulated for oral administration to the subject. Such formulations, and methods of using the same, may also deter diversion, inhibit peripheral effects of the opioid agonist, and reduce addiction liability.

Abstract: This invention relates a therapeutic pharmaceutical composition comprising: a mixture including an opioid; polyethylene oxide in an amount of about 3 to about 40 wt % of the composition; a disintegrant; and a surfactant; wherein the disintegrant is present in an amount sufficient to cause the pharmaceutical composition to exhibit an immediate release profile.

Abstract: A method of preparing a thin film, the method comprising: (a) mixing a lipid, emulsifier, and solvent to provide a uniform first mixture; (b) contacting an active ingredient with the uniform first mixture to provide a thickened second mixture; (c) contacting a binder with the thickened second mixture to provide a slurry; and (d) hot extruding, casting, and condensing the slurry to provide the thin film; or cooling, shearing, mixing, casting, and condensing the slurry to provide the thin film.

Abstract: A method for treating, preventing or reducing the risk of joint destruction in a subject who suffers from a joint or musculoskeletal disease. The method comprises administering a histone deacetylase (HDAC) inhibitor or in conjunction with other agents to inhibit degradation and resorption of cartilage and bone in the joint.

Abstract: A non-addictive analgesic co-formulation comprising an opioid agonist in an amount sufficient to confer analgesia in a mammalian subject and a neutral opioid antagonist in an amount sufficient to inhibit peripheral effects, and insufficient to block substantial central effects, of the opioid agonist in the subject. Such formulations, and methods of using same, may also deter diversion, inhibit peripheral effects, and reduce addiction liability.

Abstract: The present invention relates to co-extruded pharmaceutical compositions and dosage forms including an active agent, such as an opioid agonist, and an adverse agent, such as an opioid antagonist. Such compositions and dosage forms are useful for preventing or discouraging tampering, abuse, misuse or diversion of a dosage form containing an active pharmaceutical agent, such as an opioid. The present invention also relates to methods of treating a patient with such a dosage form, as well as kits containing such a dosage form with instructions for using the dosage form to treat a patient.

Abstract: The invention provides 3-carboxypropyl-aminotetralin compounds of formula (I): wherein R1, R2, R3, R4, R5, and R6 are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are antagonists at the mu opioid receptor. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat conditions associated with mu opioid receptor activity, and processes and intermediates useful for preparing such compounds.

Abstract: This disclosure relates to novel morphinan compounds and their derivatives, pharmaceutically acceptable salts, solvates, and hydrates thereof. This disclosure also provides compositions comprising a compound of this disclosure and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering a ?1 receptor agonist that also has NMDA antagonist activity.

Abstract: The invention pertains to a method of using oxymorphone in the treatment of pain by providing a patient with an oxymorphone dosage form and informing the patient or prescribing physician that the bioavailability of oxymorphone is increased in patients with renal impairment.

Abstract: Provided herein is a pharmaceutical composition comprising an antagonist, an agonist, a seal coat, and a sequestering polymer, wherein the antagonist, agonist, seal coat and at least one sequestering polymer are all components of a single unit, and wherein the seal coat forms a layer physically separating the antagonist from the agonist from one another. Methods for manufacturing such a pharmaceutical composition are also provided.

Abstract: A composition for controlled release of an opioid from a pharmaceutical composition, the method comprises controlling the release of at least one opioid into an aqueous medium by erosion of at least one surface of a pharmaceutical composition comprising I) a matrix composition comprising a) polymer or a mixture of polymers, b) an opioid and, optionally, c) one or more pharmaceutically acceptable excipients, and (i) a coating. The matrix composition has a conus-like shape so the surface area exposed to the aqueous medium increases at least during initial erosion of the matrix composition, and the dissolution of the opioid—when tested in a Dissolution Test as described herein with or without application of sinkers-results in a zero order release of at least 80% of the opioid contained in the composition. Such compositions are especially suitable for controlled release of an opioid to obtain a delayed peak concentration and a prolonged therapeutically effective plasma concentration upon oral administration.

Abstract: Provided herein is a pharmaceutical composition comprising an antagonist, an agonist, a seal coat, and a sequestering polymer, wherein the antagonist, agonist, seal coat and at least one sequestering polymer are all components of a single unit, and wherein the seal coat forms a layer physically separating the antagonist from the agonist from one another. Methods for manufacturing such a pharmaceutical composition are also provided.

Abstract: The invention relates to the use of a group of sigma receptor ligands of formula (I) for the potentiation of the analgesic effect of opioids and opiates and at the same time for decreasing the dependency induced by them.

Abstract: The invention relates to an oral pharmaceutical composition in the form of a sustained-release tablet comprising an active ingredient capable of being misused, which composition makes it possible to combat misuse by injection.

Abstract: The aspects of the present disclosure are directed to novel compounds, formulations containing said compounds or pharmaceutically acceptable salts thereof which are suitable for administration to a patient. In particular, to 5-methyldihydromorphone prodrug compounds described in general Formula I and II and the use of the compounds for treating pain associated with a variety of chronic human disorders including for example neuropathic pain and pain associated with cancer, surgeries or injuries.

Abstract: Disclosed herein are oral solid dosage forms comprising purified neutral acrylic polymer, methods of treating a disease or condition using the same, and methods of preparing the same.

Abstract: The invention relates to a dosage form comprising a physiologically effective amount of a physiologically active substance (A), a synthetic, semi-synthetic or natural polymer (C), optionally one or more physiologically acceptable auxiliary substances (B) and optionally a synthetic, semi-synthetic or natural wax (D), wherein the dosage form exhibits a resistance to crushing of at least 400 N and wherein under physiological conditions the release of the physiologically active substance (A) from the dosage form is at least partially delayed.

Abstract: Methods and systems for administration of pharmaceuticals using a unit dosage package that includes a first unit dosage that has a first drug and a second drug, a second unit dosage that has the first drug and the second drug, where the second unit dosage includes a different amount of the second drug than the first unit dosage and a unit dosage package is configured to hold the first unit dosage and the second unit dosage. In preferred embodiments the methods and systems are used for administration of weight loss medications.

Abstract: Methods and compositions for treating a blood glucose condition involve identifying a suitable subject and administering an effective amount of a composition that contains one or more of an opioid antagonist, an anticonvulsant, and a psychotherapeutic agent. The compositions can include insulin. In some embodiments, such methods and compositions can be used to modulate a blood glucose level. In preferred embodiments, such methods and compositions are useful for increasing a subject's sensitivity to insulin.

Abstract: The invention provides methods of attenuating, e.g., inhibiting or reducing, cellular proliferation and migration, particularly endothelial cell proliferation and migration, including that associated with angiogenesis, using opioid antagonists, including, but not limited to, those that are peripherally restricted antagonists.

Abstract: The present invention generally relates to processes for preparing highly pure morphinan-6-one products. The processes involve reducing the concentration of ?,?-unsaturated ketone compounds present as impurities in morphinan 6 one products or reaction mixtures including morphinan 6 one compounds by treatment with a sulfur-containing compound.

Abstract: The presently described technology provides phenylethanoic acid, phenylpropanoic acid, phenylpropenoic acid, a salt thereof, a derivative thereof or a combination thereof chemically conjugated to hydrocodone (morphinan-6-one, 4,5-alpha-epoxy-3-methoxy-17-methyl) to form novel prodrugs or compositions of hydrocodone which have a decreased potential for abuse of hydrocodone. The present technology also provides methods of treating patients, pharmaceutical kits and methods of synthesizing conjugates of the present technology.

Abstract: The present invention is directed to a combination treatment for: individuals who meet the definition of food addiction; individuals that are overweight or obese (e.g., a BMI?25); individuals that have a binge eating disorder; or individuals who engage in a binge eating behavior. In particular embodiments, the combination therapy reduces the intake of fatty foods, sugar rich foods, or foods that are both fatty and sugar-rich (e.g., such as fast foods).

Abstract: The invention includes methods of neuroprotection, inducing release of neurotrophic factors, inhibiting the over-activation of innate immune cells, attenuating the toxin-induced death and/or damage of tissues, reducing inflammation, treating an inflammation-related condition, and inhibiting NADPH oxidase, that includes contacting or administering an effective amount of at least one compound of the invention that include: valproic acid, sodium butyrate, and salts thereof; opioid peptides; a peptide comprising the tripeptide GGF; and morphinans, such as naloxone, naltrexone, 3-hydroxy-morphinan and dextromethorphan.

Abstract: A dissolving solid solution perforator (SSP) patch for oral cavity administration may include at least one perforator. The at least one perforator may contain a first drug and be configured to pierce an outside layer of an oral cavity for promptly delivering the first drug. The at least one perforator may penetrate an epithelium layer of the oral cavity and to deliver the antimigraine drug into blood vessels in a submucosa layer.

Abstract: The present invention is drawn to adhesive solid gel-forming formulations, methods of drug delivery, and solidified gel layers for dermal delivery of a drug. The formulation can include a drug, a solvent vehicle, and a gelling agent. The solvent vehicle can include a volatile solvent system having one or more volatile solvent, and a non-volatile solvent system having one or more non-volatile solvent, wherein at least one non-volatile solvent is flux-enabling non-volatile solvent(s) capable of facilitating the delivery of the drug at therapeutically effective rates over a sustained period of time. The formulation can have a viscosity suitable for application to a skin surface prior to evaporation of the volatile solvents system. When applied to the skin, the formulation can form a solidified gel layer after at least a portion of the volatile solvent system is evaporated. The solidified gel layer is can be removed by peeling or washing.

Abstract: Sustained release formulations of nalbuphine or pharmaceutically acceptable salts thereof; methods for making the sustained release formulations of nalbuphine or pharmaceutically acceptable salts thereof; and methods for using the sustained release formulations of nalbuphine or pharmaceutically acceptable salts thereof to treat patients suffering from pain are provided.

Abstract: The present invention relates to (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane and pharmaceutically acceptable salts thereof, compositions comprising (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof, and methods for treating or preventing an alcohol-related or addictive disorder. The (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.

Abstract: Methods and materials related to the use of morphine, morphine precursors (e.g., reticuline), and inhibitors of morphine synthesis or activity to treat diseases, to reduce inflammation, or to restore normal function are provided.

Abstract: A treatment is described for diseases with symptoms that can include fatigue, muscle aches and spasms, weakness, demylenation, and nerve pain. Diseases can include fibromyalgia, depression, and auto-immune and immuno-suppressive diseases, such as MS. The treatment comprises about 1-10 mg naltrexone, at least about 20 ?g vitamin B12, at least about 5 mg vitamin B6, at least about 2 mg coenzyme Q, and preferably at least one ancillary medication selected from the group consisting of diazepam, cyclcobenzaprine, clonazepam, alprazolam, 9-tetrahydrocannibinol, fumarate, caffeine, and combinations thereof. The treatment can be administered orally, and can decrease mental and physical symptoms such as, for example, fatigue, gait problems, visual dysfunction, and pain while improving cognitive skills.