Abstract: According to this invention, compositions and methods for increasing the extent of penetration of a biologically active substance into the tissues and organs are proposed, the methods comprising administration of the biologically active substance in combination with one or more chaotropic agents, e.g., ammonium sulfate.

Abstract: The present invention is related to insulin derivatives containing additional disulfide bonds and methods of making such.

Abstract: The present invention relates to the finding that certain DPP-4 inhibitors are particularly suitable for treating and/or preventing metabolic diseases, particularly diabetes, in patients for whom metformin therapy is inappropriate due to intolerability or contraindication against metformin.

Abstract: The present invention provides materials and methods to facilitate the transcutaneous delivery of therapeutic agents. In some embodiments, agonists of tight junctions are used in compositions to facilitate the uptake of therapeutic agents from the skin. In a particular embodiment, the present invention provides immunogenic compositions comprising a tight junction agonist and an antigen. In a particular embodiment, the present invention provides vaccine compositions comprising a tight junction agonist and an antigen.

Abstract: An equipment assembly for preparing, harvesting and collecting particles is disclosed. The assembly comprises a tandem filter system with one or more high pressure filters, one or more low pressure filters and one or more collection vessel. Particles can be prepared, harvested and collected continuously, semi-continuously or in a batch-type operation. A tandem filter system and its method of use are also disclosed. Particles made with the assembly and according the instant methods are also disclosed. The assembly provides improved particle harvesting and collection over other systems and permits continuous particle formation, in particular by dispersion of a solute-containing process fluid within a supercritical anti-solvent.

Abstract: Embodiments are directed to compositions and methods of treating migraine and related neurological disorders. In certain aspects, methods and compositions are for reducing cortical spreading depression and/or suppressing the neurochemical basis for chronic and acute migraine events, and provide methods and pharmaceutical compositions related to both acute and preventive therapies for migraine events and related headaches.

Abstract: The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.

Abstract: The invention provides pharmaceutical compositions, methods for the treatment of and related diagnostics and computer-implementable systems that relate to, the treatment of a variety of metabolic syndromes, including hyperlipidemia, weight gain, obesity, insulin resistance, hypertension, atherosclerosis, fatty liver diseases and certain chronic inflammatory states. In an additional aspect of the invention, compositions and methods of treatment are calibrated to the ileal brake response to surgical intervention e.g. RYGB, as both activate the ileal brake, which acts in the gastrointestinal tract and the liver of a mammal to control metabolic syndrome manifestations and thereby reverse or ameliorate the cardiovascular damage (atherosclerosis, hypertension, lipid accumulation, and the like) resulting from progression of metabolic syndrome.

Abstract: Method for preparing an oxidized polysaccharide-protein composition, by (a) oxidizing a polysaccharide with an oxidizing agent to form an oxidized polysaccharide where less than 20% of the oxidized units are comprised of alpha-hydroxy aldehyde units, (b) reacting the oxidized polysaccharide with a protein to form a composition comprising an oxidized polysaccharide-protein conjugate, and (c) maintaining the oxidized polysaccharide-protein conjugate composition by placing it in an environment where the temperature is less than 8° C. The oxidized polysaccharide and the protein are conjugated via one or more imine bonds, the oxidized polysaccharide-protein composition is soluble in aqueous solvent, and the composition is capable of releasing the protein.

Abstract: Disclosed herein are diketopiperazine microparticles having a specific surface area of less than about 67 m2/g. The diketopiperazine microparticle can be fumaryl diketopiperazine and can comprise a drug such as insulin.

Abstract: The present invention relates to a liposomal formulation for oral delivery of a bioactive agent that considers pH stability and oxidative stability of a bioactive ingredient. These lipid formulations are superior to conventional liposomes due to their stability, thereby circumventing the need for intra-venous delivery of bioactive agents. In one embodiment, the methods and compositions of the present invention relate to the oral delivery of insulin or a prodrug thereof.

Abstract: The present invention relates to compounds and pharmaceutically acceptable salts thereof and formulations comprising the compounds or a pharmaceutically acceptable salts thereof that are useful in modulating lyn kinase activity. In particular, the compounds or a pharmaceutically acceptable salts thereof are useful for treating or preventing a disease or disorder including cardiovascular disease, dyslipidemia, dyslipoproteinemia, a disorder of glucose metabolism, metabolic syndrome (i.e., Syndrome X), a peroxisome proliferator activated receptor-associated disorder, septicemia, a thrombotic disorder, type II diabetes, obesity, pancreatitis, hypertension, renal disease, inflammation, or impotence.

Abstract: Provided is a conjugate including a pharmacologically active substance covalently bound to chitosan or its derivative and a method for transmucosal delivery of a pharmacologically active substance using the same. Specifically a conjugate includes a pharmacologically active substance covalently bound via a linker to chitosan; and a pharmaceutical composition for transmucosal administration of a drug includes the aforementioned conjugate and a pharmaceutically acceptable carrier. Further provided is a method for in vivo delivery of a pharmacologically active substance via a transmucosal route, by covalent binding of the active substance with chitosan or its derivative via a linker.

Abstract: A formulation for administration of at least one therapeutic mammalian protein to a mammal or a protein selected from the group, and for enhancing the absorption, distribution and release of the at least one therapeutic mammalian protein in or on the mammal, comprising at least one therapeutic mammalian protein in a micro-emulsion comprising a dispersion of vesicles or microsponges of a fatty acid based component in an aqueous or other pharmacologically acceptable carrier in which nitrous oxide is dissolved, the fatty acid based component comprising at least one long chain fatty acid based substance selected from the group consisting of free fatty acids and derivatives of free fatty acids. A method for effective delivery of at least one therapeutic mammalian protein to a mammal and for enhancing the therapeutic efficacy of such at least one therapeutic mammalian protein, comprising the step of administering the at least one therapeutic mammalian protein to the mammal in such a formulation.

Abstract: Methods for delivering an effective amount of insulin to the central nervous system to treat Social Communication Disorder while minimizing systemic exposure to the administered insulin. The present invention provides these advantages by administering at least an effective amount of insulin and/or pharmaceutical composition(s) thereof, to the upper third of the nasal cavity, thereby bypassing the blood-brain barrier and delivering an effective amount of insulin and/or pharmaceutical compound(s) thereof directly to the CNS. Further methods comprise administering an at least an effective amount of therapeutic agents to the amniotic fluid surrounding a fetus with a treatable neurologic agent or a preventable neurologic condition. For example, administering the at least effective amount of insulin to the amniotic fluid of a fetus with a mother diagnosed with gestational diabetes may prevent the fetus from developing Social Communication Disorder or autism.

Abstract: The invention is related to pharmaceutical compositions suitable for oral administration of insulin peptides, methods of making such and treatment with such.

Abstract: The disclosure provides cross-linked materials that include multivalent cross-linking agents that bind an exogenous target molecule; and conjugates that include two or more separate affinity ligands bound to a conjugate framework, wherein the two or more affinity ligands compete with the exogenous target molecule for binding with the cross-linking agents and wherein conjugates are cross-linked within the material as a result of non-covalent interactions between cross-linking agents and affinity ligands on different conjugates. The conjugates also include a drug.

Abstract: The present invention relates to a method for the early diagnosis of a clinically latent placental insufficiency in pathological placental maturation, and the prophylaxis of an intrauterine fetal hypoxia/asphyxia at the due date or after a prolonged gestation, comprising determining the amount and/or the concentration of the biomarker prokineticin 1 (EG-VEGF) and/or its receptor PKR1 and/or PKR2 in a sample from the pregnant subject and/or the pregnancy. In a preferred embodiment, the invention is based on determining the ratio of the amount and/or the concentration of bFGF/PK1 as a measure of current functional condition and an indicator of latent clinical problems such as placental dysfunction resulting in fetal hypoxia.

Abstract: The invention relates to a composition in the form of an injectable aqueous solution, the pH of which is between 6.6 and 7.8, including at least: a) a basal insulin, the isoelectric point pI of which is between 5.8 and 8.5; and b) a hydrophobized anionic polymer. In one embodiment, the compositions according to the invention also includes a prandial insulin.

Abstract: Disclosed are novel methods for making cochleates and cochleate compositions that include introducing a cargo moiety to a liposome in the presence of a solvent. Also disclosed are cochleates and cochleate compositions that include an aggregation inhibitor, and optionally, a cargo moiety. Additionally, anhydrous cochleates that include a protonized cargo moiety, a divalent metal cation and a negatively charge lipid are disclosed. Methods of using the cochleate compositions of the invention, including methods of administration, are also disclosed.

Abstract: The present invention is related to insulin analogs containing additional disulfide bonds and methods of making such.

Abstract: A composition in the form of an injectable aqueous solution, the pH of which is from 6.6 to 7.8, comprises at least: a) a basal insulin, the isoelectric point pI of which is between 5.8 and 8.5; and b) an anionic compound bearing carboxylate charges and hydrophobic radicals. The composition may also include a prandial insulin.

Abstract: Embodiments of the invention provide swallowable devices, preparations and methods for delivering drugs and other therapeutic agents within the GI tract. Many embodiments provide a swallowable device for delivering the agents. Particular embodiments provide a swallowable device such as a capsule for delivering drugs into the intestinal wall or other GI lumen. Embodiments also provide various drug preparations that are configured to be contained within the capsule, advanced from the capsule into the intestinal wall and degrade to release the drug into the bloodstream to produce a therapeutic effect. The preparation can be operably coupled to delivery means having a first configuration where the preparation is contained in the capsule and a second configuration where the preparation is advanced out of the capsule into the intestinal wall. Embodiments of the invention are particularly useful for the delivery of drugs which are poorly absorbed, tolerated and/or degraded within the GI tract.

Abstract: This invention relates to a method of reducing cardiovascular morbidity and mortality in a prediabetic or Type 2 Diabetes patient population. The method comprises administering an effective dosage of a long acting insulin, preferably insulin glargine, to a prediabetic or Type 2 Diabetes patient.

Abstract: Drug delivery systems have been developed based on the formation of diketopiperazine carboxylate salts and microparticles containing the same. The systems may further comprise a bioactive agent. Related methods for making and using the biologically active agent delivery compositions are also provided. In certain embodiments, the pharmaceutically acceptable salts described can be formed by removal of solvent by methods including distillation, evaporation, spray drying or lyophilization.

Abstract: Vesicle compositions are provided that comprise a therapeutic compound. The vesicle compositions may be capable of releasing the therapeutic compound in response to the presence of an external trigger. The vesicle compositions may comprise a plurality of biocompatible vesicles. The biocompatible vesicles may comprise a therapeutic compound for treatment of a patient in need thereof, and one or more cross-linkages between two or more of the biocompatible vesicles, each cross-linkage comprising a chemical sensing moiety and a sensed moiety. In some embodiments, the therapeutic compound may be any compound that provides palliative, curative, or otherwise beneficial effects to a patent.

Abstract: The present invention relates to methods for making a stabilized powder formulation for inhalation comprising a macromolecule in lyophilized form, a crystalline carrier material, and magnesium stearate.

Abstract: Nanoparticles having a core and a corona of ligands covalently linked to the core, wherein an active agent and a permeation enhancer are bound to or associated with the nanoparticles.

Abstract: Derivatives are synthesised of starting materials, usually polysaccharides, having sialic acid at the reducing terminal end, in which the reducing terminal unit is transformed into an aldehyde group. Where the polysaccharide has a sialic acid unit at the non-reducing end it may be passivated, for instance by converting into hydroxyl-substituted moiety. The derivatives may be reacted with substrates, for instance containing amine or hydrazine groups, to form non-cross-linked polysialylated compounds. The substrates may, for instance, be therapeutically useful drugs peptides or proteins or drug delivery systems.

Abstract: The invention provides compositions and methods for determining GLP-1 analog and/or DPPIV inhibitor response in a subject. In one embodiment, the composition comprises a solid support comprising probes for measuring a biomarker panel comprising, for example, adiponectin, C-peptide, hsCRP, insulin, proinsulin. The simultaneous use of multiple biomarkers with independent classification power will increase the performance of the biomarker panel in characterizing GLP-1 analog and DPPIV inhibitor response. The invention also provides methods of treating a subject (e.g. one experiencing cardiodiabetes) and determining the efficacy of a therapy through assaying the various biomarkers of a biomarker panel disclosed herein.

Abstract: Novel human insulin derivatives are described which are soluble at physiological pH values and have a prolonged profile of action.

Abstract: The present invention provides therapeutic agents and compositions comprising elastic peptides and therapeutic proteins. Such peptides exhibit a flexible, extended conformation. In some embodiments, the therapeutic protein is a GLP-1 receptor agonist (e.g., GLP-1, exendin), insulin, or Factor VII/VIIa, including functional analogs. The present invention further provides encoding polynucleotides, as well as methods of making and using the therapeutic agents. The therapeutic agents have improvements in relation to their use as therapeutics, including, inter alia, one or more of half-life, clearance and/or persistance in the body, solubility, and bioavailability.

Abstract: Macrocyclic compounds that specifically inhibit insulin degrading enzyme (IDE) are provided. Pharmaceutically acceptable salts, solvates, hydrates, stereoisomers, polymorphs, tautomers, isotopically enriched forms, and prodrugs of the macrocyclic IDE inhibitors are also described. Pharmaceutical compositions are also provided. In vivo and in vitro methods of using the IDE inhibitor, and pharmaceutical compositions comprising the IDE inhibitor, for example, for the inhibition of IDE in a subject exhibiting aberrant IDE activity, impaired insulin signaling, or insulin resistance, for example, a subject having diabetes, are also provided.

Abstract: Novel pro-insulin having specific amino acid and/or nucleic acid modifications suitable for improved methods of insulin production are provided. Novel and highly efficient processes for preparing the pro-insulin preparations and preparations containing them are also disclosed. The novel pro-insulin preparations may be converted into human insulin useful in therapeutic preparations. Novel peptides of the C-peptide, and N terminus, including RREAEALQVGQVELGGGPGAGSLQPLALEGSLQAR, and MHHHHHHGGR respectively are provided, as well as the unique nucleic acid molecules encoding them.

Abstract: A method of synthesizing PHA nanocapsules as a protein carrier, particularly, the synthesis of PHA nanocapsules synthesized by a modified precipitation/solvent evaporation technique with neutralization. Specifically, the method comprises the steps of sonicating a first solution comprising a triblock PHA copolymer, stirring the first solution into a second solution to give a third solution, the second solution containing a protein, and the second solution being acidic. Further, the method comprises adding the third solution with a neutralizing agent to give a neutralized solution, and sonicating the neutralized solution to form a final solution, wherein the synthesized PHA nanocapsules containing the protein are formed in the final solution. Further, PHA nanocapsules encapsulated with the protein is used by administering the synthesized PHA nanocapsule to an animal in need thereof via the oral cavity.

Abstract: The application relates to an aqueous pharmaceutical formulation comprising 200-1000 U/mL [equimolar to 200-1000 IU human insulin] of insulin glargine.

Abstract: The present invention provides pharmaceutical compositions comprising of at least one delivery agent and GLP-1. These pharmaceutical compositions facilitate the oral delivery of GLP-1, providing improved (e.g. increased) bioavailability of GLP-1 compared to administration of GLP-1 without a delivery agent.

Abstract: This invention relates to a method for detecting the presence of or likelihood of a patient of developing occult pancreatic beta cell dysfunction, and a method for detecting the presence of or likelihood of a patient of developing clinically significant post-prandial hyperglycemia. The methods involve (a) measuring a level of alpha-hydroxybutyrate (AHB) in a single fasting baseline biological sample of the patient; (b) comparing the level of AHB in the single fasting baseline biological sample to a reference AHB level; and (c) determining the presence of or likelihood of developing the disorder in the patient based on the comparison in step (b). An increased AHB level at fasting baseline indicates that a normoglycemic, normo-insulinemic and/or non-dyslipidemic patient has developed or has an increased likelihood of developing occult pancreatic beta cell dysfunction.

Abstract: Disclosed herein are diketopiperazine microparticles having high capacity for adsorbing a drug or active agent. In particular, the diketopiperazine microparticle are formed using fumaryl diketopiperazine and can comprise a drug in large doses for the treatment of disease or disorders by pulmonary delivery via oral inhalation.

Abstract: Buccal aerosol sprays or capsules using polar and non-polar solvent have now been developed which provide biologically active compounds for rapid absorption through the oral mucosa, resulting in fast onset of effect. The buccal polar compositions of the invention comprise formulation I: aqueous polar solvent, active compound, and optional flavoring agent; formulation II; aqueous polar solvent, active compound, optionally flavoring agent, and propellant; formulation III: non-polar solvent, active compound, and optional flavoring agent; and formulation IV: non-polar solvent, active compound, optional flavoring agent, and propellant.

Abstract: This invention relates to a method for detecting the presence of or likelihood of a patient of developing occult pancreatic beta cell dysfunction, and a method for detecting the presence of or likelihood of a patient of developing clinically significant post-prandial hyperglycemia. The methods involve (a) measuring a level of alpha-hydroxybutyrate (AHB) in a single fasting baseline biological sample of the patient; (b) comparing the level of AHB in the single fasting baseline biological sample to a reference AHB level; and (c) determining the presence of or likelihood of developing the disorder in the patient based on the comparison in step (b). An increased AHB level at fasting baseline indicates that a normoglycemic, normo-insulinemic and/or non-dyslipidemic patient has developed or has an increased likelihood of developing occult pancreatic beta cell dysfunction.

Abstract: Compositions and methods for treating neural dysfunction. A exemplary method comprises administering to a subject having a neuropathy, e.g., a cognitive dysfunction or Alzheimer's, a therapeutically effective amount of an insulin or insulin analog, wherein the insulin or insulin analog crosses the BBB and/or a compound that increases SREBP-2 expression or activity in the CNS of the subject.

Abstract: The present invention relates to alkylglycoside-containing compositions and methods for increasing the stability, reducing the aggregation and immunogenicity, increasing the biological activity, and reducing or preventing fibrillar formation of insulin or an analog thereof.

Abstract: The present invention relates to an insulin preparation that contains a self-assembling peptide. More specifically, the present invention is an insulin preparation containing a self-assembling peptide of SEQ ID NO:1.

Abstract: A pharmaceutically delivery system is described comprising a pharmaceutically active agent and acidified nitrite as an agent to produce local production of nitric oxide at the skin surface. The dosage form may be in any pharmaceutically acceptable carrier means and comprises an acidifying agent adapted to reduce the pH at the environment. In one embodiment, a barrier consisting of a membrane allows diffusions of the anaesthetic and nitrite ions while preventing direct contact of the skin and acidifying agent.

Abstract: Methods for preconditioning and/or providing neuroprotection to the animal central nervous system against the effects of cerebral hemorrhage and subarachnoid hemorrhage. Therapeutic agents are administered to the upper third of the nasal cavity to bypass the blood-brain barrier and access the central nervous system directly to avoid unwanted and potentially lethal side effects. Therapeutic agents include those substances that interact with iron and/or copper such as iron chelators, copper chelators, and antioxidants. A particular example of such therapeutic agents is the iron chelator deferoxamine (DFO). An effective amount of DFO may be administered to the upper third of the nasal cavity of a patient at risk for, or diagnosed with, cerebral hemorrhage and subarachnoid hemorrhage. The effective amount of DFO is delivered directly to the patient's central nervous system for preconditioning, preventing and/or treating the cerebral hemorrhage and subarachnoid hemorrhage.

Abstract: Provided herein are albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins and vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins and using these nucleic acids, vectors, and/or host cells also are provided. Further described are pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

Abstract: Intranasal insulin is beneficial for the treatment of Alzheimer's disease and other neurologic disorders. But commercial insulin preparations use metacresol, phenol, and other preservatives for chemical stabilization. Metacresol in particular has multiple toxic effects when administered long term, especially intranasal. These effects include rhinitis and nosebleeds. The present invention teaches the use of intranasal insulin not preserved with meta-cresol, phenol or other excipients for the treatment of Alzheimer's disease and other neurologic disorders.

Abstract: Stable formulations for parenteral injection of peptide drugs and methods of using such stable formulations are provided. In particular, the present invention provides stable formulations for parenteral injection of glucagon and methods of using such glucagon formulations to treat hypoglycemia, especially severe hypoglycemia in emergency situations.

Abstract: The use of Kruppel-like Factor (KLF10) as a diagnostic and prognostic tool for peripheral artery disease and other disease conditions associated with reduced angiogenesis or endothelial progenitor cell dysfunction such as diabetes and stent thrombosis.