Abstract: Disclosed are a method and composition for the prevention or treatment of diabetic angiogenesis impairment or diabetic wound-healing impairment, using C-peptide. Found to be able to induce angiogenesis through chemotactic migration of endothelial cells, cell migration to wounded areas, capillary-like network formation, and extracellular signal-regulated kinases 1/2 and Akt phosphorylation and nitric oxide production, C-peptide has prophylactic or therapeutic applications in a broad spectrum of various diabetic complications including diabetic angiogenesis impairment.

Abstract: A precursor of a molecular probe for imaging of pancreatic islets is provided.

Abstract: In one aspect, the disclosure provides cross-linked materials that include multivalent lectins with at least two binding sites for glucose, wherein the lectins include at least one affinity ligand which is capable of competing with glucose for binding with at least one of said binding sites and is covalently linked to a cysteine residue of the lectins; and conjugates that include two or more separate affinity ligands bound to a conjugate framework, wherein the two or more affinity ligands compete with glucose for binding with the lectins at said binding sites and wherein conjugates are cross-linked within the material as a result of non-covalent interactions between lectins and affinity ligands on different conjugates. These materials are designed to release amounts of conjugate in response to desired concentrations of glucose. Depending on the end application, in various embodiments, the conjugates may also include a drug and/or a detectable label.

Abstract: Novel acylated insulin analogues exhibiting resistance towards proteases can, effectively, be administered pulmonary or orally. The insulin analogues contain B25H and A14E or A14H.

Abstract: The present invention provides a pharmaceutical composition formulated for oral delivery, comprising a particulate non-covalently associated mixture of pharmacologically inert silica nanoparticles having a hydrophobic surface, a polysaccharide, and a biologically active protein or peptide suspended in an oil. The present invention further provides methods of manufacturing same and therapeutic methods utilizing same for oral delivery of a therapeutic protein or peptide.

Abstract: This document relates to conjugates of a biologically active molecule or a derivative thereof and functionalized (e.g., mono- or bi-functional) polymers (e.g., polyethylene glycol and related polymers) as well as methods and materials for making and using such conjugates.

Abstract: Disclosed herein are systems and methods for stimulating meibomian gland epithelial cell function by administering to the ocular surface or immediate vicinity of an eye of a subject an effective amount of a pharmaceutical composition containing a PLD-inducing compound, such as the cationic amphiphilic drugs (e.g. azithromycin), androgen or an androgen analogue with androgen effectiveness, corticosteroid, progesterone, IGF-1 or an IGF-1 analogue (e.g. insulin), GH, and mixtures thereof. The pharmaceutical compositions are effective to treat a variety of aliments to the eye including meibomian gland dysfunction, evaporative dry eye disease, lipid abnormalities in meibum or the tear film, and autoimmune diseases such as Sjögren's syndrome.

Abstract: Compositions, methods of making, and methods of using nanoclusters in which the nanoclusters comprise a plurality of nanoparticles having a core of nanoparticles arranged such that the surfaces of the nanoparticles contact adjacent nanoparticles, the nanoparticles comprise an active ingredient, and the nanocluster has a mass median aerodynamic diameter of from about 0.25 ?m to about 20 ?m.

Abstract: The invention concerns a soluble pharmaceutical formulation comprising an insulin derivative wherein the formulation further comprises more than 4 zinc atoms per 6 molecules of the insulin derivative, and a citric acid monohydrate and/or a histidine compound used in an amount sufficient to increase the tendency of the insulin derivative to self-associate into dodecamers. The invention further comprises a process for preparing the soluble pharmaceutical formulation.

Abstract: Provided are methods for control of post-prandial glucose in diabetic subjects by administering a fast-acting insulin analog and a hyaluronidase degrading enzyme. The fast-acting insulin analog and a hyaluronidase are administered between 15 minutes before the meal and 30 minutes after commencing the meal.

Abstract: The present invention is embodied by a composition capable of chaperoning a typically non-orally available therapeutic or diagnostic agent through the environment of the digestive tract such that the therapeutic or diagnostic agent is bioavailable. The composition may or may not be targeted to specific cellular receptors, such as hepatocytes. Therapeutic agents include, but are not limited to, insulin, calcitonin, serotonin, and other proteins. Targeting is accomplished with biotin or metal based targeting agents.

Abstract: A stable pharmaceutical formulation containing an insulin derivative can conveniently be prepared by adding glycerol, phenol, m-cresol and zinc ions to it.

Abstract: Compositions containing conjugates of heparosan polymer with at least one drug are disclosed, along with methods of production and use thereof.

Abstract: The present invention relates to means for protecting bioactive materials in mammalian food or feed formulations used to enhance the health status of mammals.

Abstract: The present invention relates to novel insulin analogues exhibiting resistance towards protease, wherein at least two amino acids are substituted and/or deleted relative to the parent insulin molecule. A method for the preparation of such insulin analogues, insulin preparations containing the insulin analogues of the invention and a method of treating diabetes mellitus using these insulin analogues is also provided.

Abstract: Methods and devices are provided for reducing a diabetic patient's foreign body immune response, including infusion site-loss and/or occlusion. Such foreign body responses are associated with the treatment of the diabetic patient where the treatment requires subcutaneous implantation of a foreign body, such as a cannula or catheter. In certain embodiments of the invention, a response-inhibiting agent is administered to a patient at the site of cannula/catheter insertion, thereby facilitating delivery of insulin to the diabetic patient and mitigating site-loss and/or occlusion over a period of time.

Abstract: An electromagnetic radiation activated device comprises a property changing material and at least one functionalized fullerene that upon irradiation of the functionalized fullerenes with electromagnetic radiation of one or more frequencies a thermally activated chemical or physical transformation occurs in the property changing material. The thermal activated transformation of the property changing material is triggered by the heating or combustion of the functionalized fullerenes upon their irradiation. The device can include a chemical agent that is embedded in the property changing material and is released when the material is heated by the functionalized fullerenes upon irradiation.

Abstract: The invention generally relates to a method for pulmonary delivery of therapeutic, prophylactic and diagnostic agents to a patient wherein the agent is released in a sustained fashion, and to particles suitable for use in the method. In particular, the invention relates to a method for the pulmonary delivery of a therapeutic, prophylactic or diagnostic agent comprising administering to the respiratory tract of a patient in need of treatment, prophylaxis or diagnosis an effective amount of particles comprising a therapeutic, prophylactic or diagnostic agent or any combination thereof in association with a charged lipid, wherein the charged lipid has an overall net charge which is opposite to that of the agent upon association with the agent. Release of the agent from the administered particles occurs in a sustained fashion.

Abstract: Insulin conjugates comprising an insulin molecule covalently attached to at least one bi-dentate linker having two arms, each arm independently attached to a ligand comprising a saccharide and wherein the saccharide for at least one ligand of the linker is fucose are disclosed. The insulin conjugates display a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule such as Con A.

Abstract: Compositions and methods for combination therapy are provided. The compositions comprise a multiple unit dosage form having both a therapeutic agent and a nutritional supplement. The combination therapy is useful for restoring a nutrient depletion associated with a particular disease state. Additionally, the combination therapy can prevent or attenuate the depletion of a nutrient caused, in whole or in part, by the co-administrated therapeutic drug. Methods of manufacturing the formulations are likewise described.

Abstract: Methods related to the treatment of diabetes and improving the efficiency of insulin utilization are provided. The method enables effective control of prandial glucose levels while reducing the risk of postprandial hypoglycemia. In particular, methods of potentiating the activity of endogenous insulin in type 2 diabetics and exogenous long-acting insulin in diabetics requiring basal insulin replacement are provided.

Abstract: The present invention relates to means and methods for enhancing intestinal function in poultry, leading to an increase in food conversion ratio and in total weight gain. Particularly, the present invention relates to insulin-containing feed formulations enhancing intestinal function and weight gain in poultry.

Abstract: A composition comprising chromium and insulin and/or a chromium-insulin complex, its method of preparation, and its use in the prevention and treatment of hypoglycemia and hypoglycemia-related conditions. This composition can be administered in numerous ways, including parenterally, intranasally, and orally. The composition stabilizes serum glucose levels and has a synergistic effect compared to chromium and insulin administered separately.

Abstract: A transdermal delivery device in the form of a transdermal delivery patch for the delivery of insulin is disclosed. The patch comprises cross-linked amidated low methoxy pectin, insulin and a transdermal transfer enhancing agent.

Abstract: The present invention provides albumin-binding probes capable of reversibly linking to short-lived amino-containing drugs and non-covalently associating with albumin in-vivo, thereby converting said drugs into inactive reactivable prodrugs having prolonged lifetime in-vivo. The invention further provides conjugates of said probes with amino-containing drugs, as well as pharmaceutical compositions and uses thereof.

Abstract: The present disclosure provides a buffered ophthalmic composition for formulation of topically administrable suspensions useful for treating eye disorders by promoting wound healing, delivery of pharmaceutically active agents, and lubricating the eye. In particular the ophthalmic composition includes a buffer solution compatible with application to a mammalian eye, wherein the buffer provides increased mechanism of action of pharmaceutically active agents as well as therapeutic qualities. The ophthalmic composition exhibits dual therapeutic action to alleviate various eye disorders as it concomitantly treats corneal ulcerations and excessive inflammation which results from various eye injuries.

Abstract: The invention provides a pharmaceutical composition comprising a mixture of (a) an active macromolecular principle, and (b) an aromatic alcohol absorption enhancer chosen from butylated hydroxy toluene, butylated hydroxy anisole and analogues and derivatives thereof, wherein the aromatic alcohol absorption enhancer is present in an amount by weight greater than or equal to that of the active macromolecular principle, and further comprises a pharmaceutical composition comprising a mixture of (a) an active macromolecular principle, (b) an aromatic alcohol absorption enhancer chosen from propyl gallate, butylated hydroxy toluene, butylated hydroxy anisole and analogues and derivatives thereof, wherein the aromatic alcohol absorption enhancer is present in an amount by weight greater than or equal to that of the active macromolecular principle, and (c) a solubilisation aid capable of increasing the solubility of the aromatic alcohol absorption enhancer in aqueous media.

Abstract: A method treating a patient includes administering a physiologically effective amount of a fibrillation-resistant insulin analogue or a physiologically acceptable salt thereof to the patient. The fibrillation-resistant insulin analogue or a physiologically acceptable salt thereof, contains an insulin A-chain sequence modified at position A8 and an insulin B-chain sequence or an analogue thereof. The fibrillation-resistant insulin analogue may exhibit thermodynamic stability similar to or exceeding that of wild-type human insulin and displays a susceptibility to fibrillation similar to or exceeding that of wild-type human insulin. An insulin analogue may display greater in vitro insulin receptor binding than normal insulin while displaying binding to IGFR less than twice that of normal insulin and less than that of fast-acting insulin analogs.

Abstract: Novel PEGylated insulin analogs exhibiting resistance towards proteases can, effectively, be administered pulmonary or orally. The insulin analogs contain B25H and A14E or A14H. The PEGylation is at B29K.

Abstract: The invention relates to use of the natural cytotoxicity receptor NKp46 for preventing and treating diabetes, including type I diabetes (TID) and type 2 diabetes. In particular, the invention provides compositions comprising a fragment of the extracellular region of NKp46 for preventing the onset and progression of diabetes.

Abstract: The apparatus and methods of the present invention are of use for the production of emulsion-based microparticles containing a biological or chemical agent. In particular, the apparatus provides a vessel; packing material situated inside such vessel and may further provide material capable of insertion into both ends of said vessel for enclosure of the packing material. In a particular embodiment, the apparatus is a packed bed apparatus. The methods include production of emulsion based microparticles containing a biological or chemical agent. The usefulness of the present invention is that the apparatus and methods of the present invention provide for a low-shear, non-turbulent, production of emulsion-based microparticles that provides a narrow, reproducible, particle size distribution, capable of use with both large and small volumes that is capable of being conveniently scaled up while providing predictable emulsion properties.

Abstract: Methods of encapsulating cargo in a microgel droplet, microgel droplets prepared according the provided methods, and methods of use thereof are disclosed. The methods of preparing cargo-encapsulated microgels generally include flowing through a flow-focusing nozzle of a microfluidic device a macromer phase, an oil phase, and a crosslinker phase to form microgel droplets by oil-water emulsion. The phases are pumped, injected, or flowed through the microfluidic device such that as the macromer phase approaches the flow focusing nozzle, the co-flowing oil phase shields the macromer from contact with the crosslinker phase until flow instability occurs and macromer phase droplets form. After flow instability occurs, the crosslinker diffuses from the crosslinker phase into the droplets in an effective amount to covalently crosslink the macromer into a microgel network encapsulating the cargo in the crosslinked macromer.

Abstract: An aqueous composition having increased protein stability is obtained by: a. determining a pH at which the protein has stability at the desired temperature; b. adding to the composition at least one displacement buffer wherein the displacement buffer has a pKa that is at least 1 unit greater or less than the pH of step (a); and c. adjusting the pH of the composition to the pH of step (a); wherein the aqueous composition does not comprise a conventional buffer at a concentration greater than about 2 mM and wherein the conventional buffer has a pKa that is within 1 unit of the pH of step (a).

Abstract: Disclosed are drug delivery systems for the delivery of small molecule and macromolecular drugs. More particularly, disclosed are substituted analogs of 3,6-di(alkyl-4 aminobutyl)-2,5-diketopiperazine (which may also be referred to DKP), their use in the formulation of both small molecule and macromolecular drugs including therapeutic, prophylactic and diagnostic agents, stabilizing agents and systems for their delivery.

Abstract: The present invention relates to the use of use of a long-acting insulin, in particular insulin glargine, in a method of reducing the risk of progression to type 2 diabetes in a patient, a method of reducing the risk of a new angina in a patient and a method of reducing the risk of a microvascular event in a patient comprising administering to said patient in need thereof a therapeutically effective dosage of a long acting insulin, wherein said therapeutically effective dosage of said long acting insulin reduces said risks.

Abstract: Generally, embodiments of the present disclosure relate to analyte determining methods and devices (e.g., electrochemical analyte monitoring systems) that have improved uniformity of distribution of the sensing layer by inclusion of a high-boiling point solvent, where the sensing layer is disposed proximate to a working electrode of in vivo and/or in vitro analyte sensors, e.g., continuous and/or automatic in vivo monitoring using analyte sensors and/or test strips. Also provided are systems and methods of using the, for example electrochemical, analyte sensors in analyte monitoring.

Abstract: The present invention is embodied by a composition capable of chaperoning a typically non-orally available therapeutic or diagnostic agent through the environment of the digestive tract such that the therapeutic or diagnostic agent is bioavailable. The composition may or may not be targeted to specific cellular receptors, such as hepatocytes. Therapeutic agents include, but are not limited to, insulin, calcitonin, serotonin, and other proteins. Targeting is accomplished with biotin or metal based targeting agents.

Abstract: The invention relates to a water-dispersible derivative of a therapeutic agent having a low water solubility that comprises at least one molecule of said agent covalently bonded to at least one molecule of a hydrocarbon derivative having a squalenic structure or the like. The invention further relates to corresponding nanoparticles.

Abstract: The present invention relates to PEGylated C-peptide derivatives comprising at least one PEG group attached to the N-terminus, which exhibit improved pharmacokinetic and biological activity in vivo.

Abstract: Methods for treating impaired glucose tolerance and early and late stage diabetes in mammals, for prophylactically sparing ?-cell function, aiding in preventing ?-cell death, preventing the onset of overt diabetes in a mammal with type 2 diabetes, treating the current level of glycemic control dysfunction of a mammal with impaired glucose tolerance or diabetes, comprising orally administering insulin and a delivery agent that facilitates insulin absorption from the gastrointestinal tract at the time of or shortly before mealtime, e.g., within about 10 minutes prior to ingestion of a meal, on a chronic basis. The methods also comprise, in addition to administering a rapid-acting insulin to provide a first insulin peak, administering a slow acting insulin to provide a second insulin peak occurring at a later time but of a longer duration.

Abstract: Provided herein are methods to generate and screen peptides that exhibit drug like stabilities in vitro and in vivo. By selecting for enzyme resistance, Applicants are able to derive peptides that are not only stable to a broad spectrum of proteases, but also stable to other drug processing enzymes such as cytochrome P450s. This approach provides a general method to the rapid development of highly stable peptides for therapeutic development and diagnosis. The peptides are further modified for oral bioavailability.

Abstract: In various embodiments, the present invention describes materials and methods for the local reprogramming of cells in a location where the treatment is applied. The invention can be used to replace lost cells or to restore function to tissue damaged due to disease, injury or genetic defect. In various embodiments, the treatment includes a semisolid hydrogel embedded with liposomes. The liposomes can contain an effector molecule or molecules. When phagocytic cells such as monocytes infiltrate the hydrogel, they encounter the liposomes and incorporate the liposomes carrying the effector molecules into the cells. In some embodiments, the effector molecules can be genetic material encoding the expression of specific proteins such as transcription factors, the expression of which can initiate the reprogramming of the cells. In other embodiments, the effector molecules can induce angiogenesis. In other embodiments, the effector molecules are tumor antigens.

Abstract: A method for treating type 1 and type 2 diabetes by administering an oral pharmaceutical formulation which comprises of insulin or its analogues amalgamated with suitable encapsulating agents and pharmaceutical excipients. The encapsulated pharmaceutical oral formulation protects insulin or its analogues from harsh milieu of the gastrointestinal tract and facilitates efficient delivery of insulin at targeted sites with sustained hypoglycemic activity.

Abstract: A breath-powered, dry powder inhaler, a cartridge, and a pulmonary drug delivery system are provided. The dry powder inhaler can be provided with or without a unit dose cartridge for using with the inhaler. The inhaler and/or cartridge can be provided with a drug delivery formulation comprising, for example, a diketopiperazine and an active ingredient, including, peptides and proteins such as insulin and glucagon-like peptide 1 for the treatment of diabetes and/or obesity. The dry powder inhaler is compact; can be provided in various shapes and sizes, colors, and comprises a housing, a mouthpiece, a cartridge placement area, and a mechanism for opening and closing the medicament cartridge. The device is easy to manufacture, provides a pre-metered single unit dose, it is relatively easy to use, and can be reusable or disposable.

Abstract: The present invention is directed to membranes composed of heterocyclic nitrogen groups, such as vinylpyridine and to electrochemical sensors equipped with such membranes. The membranes are useful in limiting the diffusion of an analyte to a working electrode in an electrochemical sensor so that the sensor does not saturate and/or remains linearly responsive over a large range of analyte concentrations. Electrochemical sensors equipped with membranes described herein demonstrate considerable sensitivity and stability, and a large signal-to-noise ratio, in a variety of conditions.

Abstract: The invention relates to biopolymer-gel based depot systems for prolonged and/or controlled release delivery of biologically active agents, methods for the manufacture of the biopolymer based gel-depots which include a biologically active agent, and uses of such biopolymer gel-depots in therapy. The biopolymer-gel based depot systems comprise a biocompatible polyaminosaccharide and/or protein; a biocompatible phosphate and/or sulphonamide compound; a biologically active agent; an aqueous insoluble alkaline earth metal phosphate; and a biocompatible glycan and/or proteoglycan.

Abstract: The instant invention is drawn to a hepatocyte targeted composition comprising insulin associated with a lipid construct comprising an amphipathic lipid and an extended amphipathic lipid that targets the construct to a receptor displayed by an hepatocyte. The composition can comprise a mixture of free insulin and insulin associated with the complex. The composition can be modified to protect insulin and the complex from degradation. The invention also includes methods for the manufacture of the composition and loading insulin into the composition and recycling various components of the composition. Methods of treating individuals inflicted with diabetes.

Abstract: Compounds that exhibit aggregation induced emission (AIE), and more particularly to water-soluble conjugated polyene compounds that exhibit aggregation induced emission. The conjugated polyene compounds can be used as bioprobes for DNA detection, G-quadruplex identification, and potassium-ion sensing. The polyenes also can be utilized as an external fluorescent marker to study conformational structures, to monitor folding processes of label-free oligonucleotides with G-rich strand sequences, and to visualize DNA bands in PAGE assay. The polyenes have applications in high-throughput anticancer drug screening and are useful for the development of efficient anti-cancer drugs. Furthermore, the present subject matter can also be used to monitor fibrillation of amyloid proteins and to facilitate the storage and delivery thereof.

Abstract: Methods are provided for purifying peptides and proteins by incorporating the peptide or protein into a diketopiperazine or competitive complexing agent to facilitate removal one or more impurities, from the peptide or protein. Formulations and methods also are provided for the improved transport of active agents across biological membranes, resulting for example in a rapid increase in blood agent concentration. The formulations include microparticles formed of (i) the active agent, which may be charged or neutral, and (ii) a transport enhancer that masks the charge of the agent and/or that forms hydrogen bonds with the target biological membrane in order to facilitate transport. In one embodiment, insulin is administered via the pulmonary delivery of microparticles comprising fumaryl diketopiperazine and insulin in its biologically active form. This method of delivering insulin results in a rapid increase in blood insulin concentration that is comparable to the increase resulting from intravenous delivery.

Abstract: Methods of generating functional human brown adipocytes, comprising exposing human stem cells, progenitor cells, or white adipocytes to culture with an differentiation cocktail that comprises one or more browning agents (e.g., one or more macromolecular crowders), and optionally one or more adipogenic agents, are described, as are populations of human brown adipocytes generated by the methods, and uses for the populations. Methods of generating functional human brown adipocytes in an individual, such as by administering a pharmaceutical composition comprising an differentiation cocktail, are also described.