Abstract: Provided is a process for the production of nano- and/or microparticles containing a therapeutically active agent embedded in a polymer matrix or encapsulated by a polymer shell, and nano- and/or microparticles obtainable by the process, said process comprising the steps of: a) providing a solution of a polymer selected from polylactide, polyglycolide, and polyester copolymers comprising copolymerized units of lactic acid and/or glycolic acid in an organic solvent S1 having limited water solubility; b) providing a solution or dispersion of a therapeutically active agent in as solvent or mixture of organic solvents S2 comprising at least 50 vol.

Abstract: A medical system comprising: an analyte sensor for receiving an analyte signal corresponding to an analyte concentration of a user; a health monitor device comprising a display unit and in communication with the analyte sensor, the health monitor device comprising a processor and memory communicably coupled to the processor, the memory including instructions stored therein that, when executed by the processor, cause the processor to: receive the analyte signal from the analyte sensor; determine the analyte concentration based on the analyte signal; calculate a recommended medication dosage based on the analyte concentration; associate a current parameter type with the recommended medication dosage; associate the current parameter type to at least one corresponding stored historical parameter type associated with a historical medication dosage; and display, on the display unit, the recommended medication dosage and the historical medication dosage.

Abstract: The present invention provides a conjugate comprising an albumin binding peptide and a cargo, compositions for directing cargos to the lymphatic system, and vaccines. The methods of the invention can be used to increase an immune response, or to treat cancer or an infectious disease.

Abstract: The present disclosure provides conjugates which comprise an insulin molecule conjugated via a conjugate framework to one or more separate ligands that include a first saccharide, and wherein the conjugate framework also comprises a fatty chain (e.g., a C8-30 fatty chain). In certain embodiments, a conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic (PK) and/or pharmacodynamic (PD) property of the conjugate is sensitive to serum concentration of a second saccharide. In certain embodiments, a conjugate is also characterized by having a protracted PK profile. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.

Abstract: The present invention relates to a novel insulin analog, use thereof, and a method for preparing the analog.

Abstract: The present disclosure provides a system for MRI. The system may obtain a plurality of echo signals relating to a subject that are excited by an MRI pulse sequence applied to the subject. The system may perform a quantitative measurement on the subject based on the plurality of echo signals. The MRI pulse sequence may include a CEST module configured to selectively excite exchangeable protons or exchangeable molecules in the subject, an RF excitation pulse applied after the CEST module configured to excite a plurality of gradient echoes, and one or more refocusing pulses applied after the RF excitation pulse. In some embodiments, the quantitative measurement may include determining various quantitative parameters including a T1, a T2, a T2*, an R2 value, an R2* value, an R2?, a B0 field, a pH value, an MWF, and an APT simultaneously.

Abstract: A method comprising: providing aqueous insulin; titrating the aqueous insulin with a mixture of small molecule anions, e.g. D- and L-amino acid esters, small D- and L-peptide pairs, and DL lactate solution, to form an insulin/anion pair solution. Titrating may be performed until the insulin/anion pair solution becomes negative by zeta potential measurement. The insulin/anion pair solution may be dialyzed to remove excess anionic polymer using a membrane sufficient to separate the insulin/anion pairs from excess small molecule anions. The insulin/anion pair solution may be dialyzed or lyophilized to remove all of the water, forming a solid of ultra-stable insulin. The positive electrostatic charge of the aqueous insulin may be confirmed by measuring a positive zeta potential value.

Abstract: The present invention provides a peptide of formula (I), or a pharmaceutically acceptable salt thereof, wherein the N-terminal group of the peptide is a monoradical of formula —NHR1; the C-terminal group of the peptide is a monoradical of formula —C(O)—R2; R1 is a monoradical selected from hydrogen and —C(O)—(C1-C20)alkyl; R2 is a monoradical selected from —OH and —NR3R4 radical; R3 and R4 are independently selected from hydrogen and (C1-C10)alkyl; “a” to “j” are integers from 0 to 1, provided that at least one of “a” to “j” is 1; and X1 represents any amino acid. The present invention also provides conjugates and compositions comprising the peptide of formula (I). The peptide can be used in the treatment or prevention of neoplastic diseases such as pancreatic cancer.

Abstract: The invention involves the coupling of compounds that can be bound by Haptocorrin (R-binder; Transcobalamin I; HC) to a target drug to improve pharmacokinetics, avoid undesirable side effects, and/or modify CNS access and localization. The pharmaceutical effect may be improved by conjugating the drug to haptocorrin binding substrate. This allows the conjugate to become bound to unsaturated haptocorrin in the blood, thereby protecting the drug from metabolism or excretion to increase protein half-life while not interfering with the efficacy of the protein drug. The conjugation may additionally prevent the drug from reaching the central nervous system or modify where the drug localizes and produces undesirable side effects such as nausea or hypophagia. Such a route also would prevent, in all case save for actual vitamin B12, binding by serum transcobalamin II (TCII), and thus not cause B12 deficiency with long term use.

Abstract: Embodiments provide devices, systems and methods for measuring a gastric emptying (GE) parameter (GEP). Many embodiments provide a swallowable capsule having three electrodes one covered by a coating which remains in the stomach but is degraded in the small intestine (SI). The electrodes are coupled to circuitry such that when the capsule is in the stomach, current flow occurs between the first two electrodes generating a first signal and in the SI current flow occurs between the second and now uncovered third electrode generating a second signal. These two signals can be transmitted and analyzed externally or by an internal controller to determine a GEP e.g., GE time. The patient may wear an external device configured to receive and analyze the signals to determine GE time. Embodiments of the invention may be used to diagnose gastroparesis and provide patient's information on when to eat meals or administer insulin after eating.

Abstract: The present invention relates to a conjugate comprising a sulfonamide of formula (I) and an active pharmaceutical ingredient such as an insulin analog comprising at least one mutation relative to the parent insulin, wherein the insulin analog comprises a mutation at position B16 which is substituted with a hydrophobic amino acid and/or a mutation at position B25 which is substituted with a hydrophobic amino acid. The present invention further relates to a sulfonamide of formula (A). Moreover, the present invention relates to an insulin analog comprising at least one mutation relative to the parent insulin.

Abstract: The invention describes novel conjugates of formula (I) of a pharmaceutical agent and a moiety capable of binding to a glucose sensing protein allowing a reversible release of the pharmaceutical agent depending on the glucose concentration.

Abstract: A drug delivery device includes a capsule, a logic circuit disposed within the capsule, and an actuator connected to the logic circuit and configured to expose an interior of the capsule to an exterior of the capsule upon activation by the logic circuit.

Abstract: This disclosure relates to compositions of isolated polypeptides and methods of their use for the treatment and prevention of disease or disease symptoms associated with MARCKS phosphorylation and/or dissociation from the cell membrane, including but not limited to allergic inflammation, asthma, chronic bronchitis, COPD, infection, hyper-reactivity, cystic fibrosis, ulcerative colitis, Crohn's disease, irritable bowel syndrome, rosacea, eczema, psoriasis, acne, arthritis, rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus.

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: The present invention relates to novel insulin analogues and derivatives thereof, such as acylated insulin analogues, and their pharmaceutical use, in particular in the treatment or prevention of medical conditions relating to diabetes, obesity and cardiovascular diseases.

Abstract: The invention provides methods of treating a subject having diabetes mellitus and/or a metabolic derangement.

Abstract: The invention provides reagents, pharmaceutical compositions and methods for the treatment of prevention of disorders and diseases related to defects in trigeminal innervation of the cornea, stem cell deficiency, nonhealing epithelial wounds and particularly to diseases such as neurotrophic keratopathy.

Abstract: Embodiments provide aerosolization device for providing aerosolized medicament to user. The aerosolization device includes conduit, aerosol generator, fluid receiving chamber, restrictor within the conduit, and indicator mechanism. Conduit has an inner wall and a mouthpiece end for causing an inspiratory flow. Aerosol generator includes a vibratable mesh laterally offset from the inner wall. Fluid receiving chamber receives liquid medicament. At least a portion of chamber is tapered such that liquid medicament is directed onto vibratable mesh for aerosolization. Restrictor defines a plurality of apertures that provide increases in pressure differential that vary with inspiratory flow rate within conduit and provide relatively laminar flow downstream of restrictor. Indicator mechanism indicates a state of flow parameters relative to a predefined range. Aerosol generator is configured to aerosolize at least a portion of liquid medicament only when flow parameters of the inspiratory flow are within range.

Abstract: Methods are described for measuring the amount of C peptide in a sample. More specifically, mass spectrometric methods are described for detecting and quantifying C peptide in a sample utilizing on-line extraction methods coupled with tandem mass spectrometric or high resolution/high accuracy mass spectrometric techniques.

Abstract: It is intended to provide a drug, a quasi-drug, a dermatological preparation for external use, or a material to be contained to drugs, quasi-drugs, dermatological preparations for external use, food products, or the like which has an excellent UCP-1 expression-promoting action and promotes conversion of adipose to brown adipose (browning). The present invention provides a UCP-1 expression promoter comprising a PPAR? activator and a Smad3 inhibitor in combination. The present invention also provides a UCP-1 expression promoter comprising a PPAR? activator, a Smad3 inhibitor, and a ?3 adrenaline receptor activator or a TGR5 activator in combination.

Abstract: An insulin analog with an improved in vitro effect compared with native insulin, a pharmaceutical composition for treating diabetes containing the insulin analog as an active ingredient, and a method for treating diabetes using the insulin analog or the pharmaceutical composition are described. A nucleic acid encoding the insulin analog, an expression vector including the nucleic acid, a transformant introduced with the expression vector, and a method of producing the insulin analog from the transformant are also described.

Abstract: A two-chain insulin analogue contains an A chain modified by (i) a monomeric glucose-binding element at or near its N terminus and (ii) a B chain modified by at or near its C terminus by an element that reversibly binds to the monomeric glucose-binding element such that this linkage is displaceable by glucose. The monomeric glucose-binding element may be phenylboronic acid derivative (optionally halogenated). The B chain may be modified by a diol-containing element derived from a monosaccharide, disaccharide or oligosaccharide, a non-saccharide diol-containing moiety or a ?-hydroxycarboxylate-containing moiety. The analogue can be manufactured by trypsin-mediated semi-synthesis. Formulations can be at strengths U-10 to U-1000 in soluble solutions at pH 7.0-8.0 with or without zinc ions at a molar ratio of 0.0-3.0 ions per insulin analogue monomer.

Abstract: Conjugates which comprise a drug and a ligand which includes a first saccharide; wherein the conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic or pharmacodynamic property of the conjugate is sensitive to serum concentration of a second saccharide. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.

Abstract: A single-chain insulin comprises a C-domain of 6 to 11 amino acid residues comprising at least two acidic residues at the N-terminal side of the C-domain and at least two basic residues at the C-terminal side of the C-domain peptide, a basic amino acid residue at the position corresponding to A8 of human insulin, and an acidic amino acid residue at the position corresponding to A14 of human insulin. The C-domain may contain a 2 to 4 amino acid joint region between the acidic and basic residues. Residues C1 and C2 may have a net negative charge of ?1 or ?2; and the remaining C-domain segment may culminates with two basic residues. A pharmaceutical composition comprises the single-chain insulin, formulated at a pH within the range 7.0 to 8.0, and may be formulated at a concentration of 0.6 mM to 5.0 mM and/or at a strength of U-100 to U-1000.

Abstract: Methods are described for measuring the amount of C peptide in a sample. More specifically, mass spectrometric methods are described for detecting and quantifying C peptide in a sample utilizing on-line extraction methods coupled with tandem mass spectrometric or high resolution/high accuracy mass spectrometric techniques.

Abstract: A method of preparing an inhalable insulin suitable for pulmonary delivery includes: dissolving an insulin raw material in an acidic solution to form a dissolved insulin solution; titrating the dissolved insulin solution with a buffer solution to form a suspension comprising micronized insulin particles; and stabilizing the micronized insulin particles.

Abstract: A nasal irrigation solution (or composition) for pre- and post-operation sinus surgery and for use as a daily nasal cleanser. The composition, which may be in a powder form, may include lactated ringers with xylitol. This composition may be mixed with sterile water prior to nasal irrigation.

Abstract: Novel encapsulated umirolimus and umirolimus polymer conjugate formulations having enhanced permeability and retention at tumor sites. Also provided are methods for treating cancer by administering the umirolimus formulations.

Abstract: Methods for treating pain using a protein solution comprising two or more of IL1-ra, sTNF-R1, sTNF-RII, IGF-I, EGF, HGF, PDGF-AB, PDGF-BB, VEGF, TGF-?1, and sIL-1RII, Compositions may also contain white blood cells and platelets.

Abstract: The application discloses Quiescin Q6 as a new biomarker for acute heart failure. Methods for determining the quantity of Quiescin Q6 in a sample from a subject are described. The quantity of Quiescin Q6 is determined by contacting the sample with one or more binding agents capable of specifically binding to Quiescin Q6.

Abstract: Methods and systems for measuring and using the oxidation-reduction potential (ORP) of a biological sample are provided. The system generally includes a test strip and a readout device for determining the ORP. The measured ORP is then used to determine characteristics relating to the fertility of the sample or the subject from which the sample was derived. Some characteristics that can be determined include the quality of a sperm sample, an oocyte or a fertilized egg. The measured ORP value can also be used to determine the specific characteristics of a spermatozoa sample, such as the morphology of the spermatozoa, the motility of the spermatozoa, the number of cells in the sample and the concentration of the cells in the sample. Knowledge of such characteristics and fertility potential can be used to identify individuals that might benefit from specific fertility treatments.

Abstract: Embodiments of the disclosure provide methods and/or compositions useful for an individual in need of treatment of a cardiac-related medical condition. In particular cases, GLP-1 is employed in a ultrasound targeted microbubble destruction (UTMD) system for delivery to cardiac tissue, thereby stimulating myocardial regeneration and, in at least some cases, reversal of cardiomyopathy.

Abstract: The invention is a composition of human insulin or insulin analog that includes specific concentrations of citrate, chloride, in some cases including the addition of sodium chloride, zinc and, optionally, magnesium chloride and/or surfactant, and that has faster pharmacokinetic and/or pharmacodynamic action than commercial formulations of existing insulin analog products.

Abstract: Described herein are bioactive peptides that are modified at one or more positions with a PEG moiety. An example of such a PEGylated bioactive peptide is a GHRH analog that is modified at one or more positions with a PEG moiety. Also described are pharmaceutically acceptable salts thereof and pharmaceutical compositions comprising such analogs or salts thereof, as well as methods, kits and uses thereof, for example for inducing or stimulating growth hormone secretion in a subject and for diagnosing, preventing or treating GH-deficient conditions in a subject.

Abstract: The invention relates to the use of a mixture of tetraethyleneglycol and amino sugars such as glucosamine or galactosamine to protect peptides and proteins and enhance their stability in solution.

Abstract: The present invention provides rapid-acting insulin and insulin analog formulations. The invention further provides delivery devices, particularly infusion sets, which allow for the rapid absorption of insulin and insulin analogs, as well as other active agents. Methods of using the insulin and insulin analog formulations as well as the insulin delivery devices for treating subjects with diabetes mellitus are also provided.

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: Provided herein are methods for treating cancer relating to inhibition of PI3K, as pharmaceutical compositions comprising a PI3K inhibitor and a PAK1 inhibitor.

Abstract: An object of the present invention is to provide a novel examination method for a cardiovascular disease. As means for achieving the object, provided is an examination method for a cardiovascular disease, the method including the steps of: measuring a concentration of cyclophilin A protein in a human blood sample; and determining a probability of development of a cardiovascular disease based on the measured concentration of cyclophilin A protein.

Abstract: Methods are provided for coating crystalline microparticles with an active agent by altering the surface properties of the microparticles in order to facilitate favorable association on the microparticle by the active agent. Types of surface properties that are altered by the disclosed methods include electrostatic properties, hydrophobic properties, and hydrogen bonding properties.

Abstract: The invention relates to an insulin analogue or its pharmaceutically acceptable salt, pharmaceutical composition with prolonged therapeutic effect, application of the insulin analogue, dosage method and method of treatment of diabetes. In more detail, the solution pertains to compounds being stable insulin analogues which are pharmaceutically active and characterized by a prolonged, flat, truly peakless course of glucose concentration vs. time during repeated administration and which do not show strong 24 hours fluctuations of glucose concentration, or the so-called “sawteeth effect”, during this time. Results of studies of compounds included in the scope of this application indicate an improvement in the effects of diabetes treatment by avoiding the hitherto occurring adverse influence of changes in glucose concentration throughout the entire day on a patient's organism, e.g.

Abstract: A method of repairing tissue includes implanting into a patient a therapeutically effective amount of a pharmaceutical composition including microparticles including a biodegradable, biocompatible material having cells of interest or fragments thereof adhered to at least a portion of a surface; and at least one substance active on the cells or their environment upon implantation of the microparticles in a patient associated with the material wherein the substances is released in a controlled or extended manner.

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: Disclosed is a method for the prevention or treatment of vascular leakage-induced diseases and diabetic retinopathy, using C-peptide. Found to prevent extravacular leakage by inhibiting VEGF-induced disassembly of VE-cadherin, C-peptide can be applied to the prevention or treatment of various diabetic complications accompanied by vascular leakage.

Abstract: This invention relates to crystals of whole antibodies and fragments thereof, and formulations and compositions comprising such crystals. More particularly, methods are provided for the crystallization of high concentrations of whole antibodies, and fragments thereof, in large batches, and for the preparation of stabilized whole antibody crystals for use alone, or in dry or slurry formulations or compositions. This invention also relates to methods for stabilization, storage and delivery of biologically active whole antibody crystals. The present invention further relates to methods using whole antibody crystals, antibody fragment crystals, or compositions or formulations comprising such crystals for biomedical applications, including biological delivery to humans and animals.

Abstract: Methods are provided for coating crystalline microparticles with an active agent by altering the surface properties of the microparticles in order to facilitate favorable association on the microparticle by the active agent. Type of surface properties that are altered by the disclosed methods include by electrostatic properties, hydrophobic properties and hydrogen bonding properties.

Abstract: A molecular probe for imaging of pancreatic islets is provided. The molecular probe includes a polypeptide represented by the following formula (1), or a polypeptide that has a homology with the foregoing polypeptide. (SEQ?ID?NO.?1) Z-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPSX-NH2?(1) Wherein “X” represents a lysine residue, an amino group of a side chain of the lysine residue being labeled with a group represented by the following chemical formula (I), wherein A represents an aromatic hydrocarbon group or an aromatic heterocyclic group; R1 represents a substituent that contains 11C, 13N, 15O, 18F, 64Cu, 67Ga, 68Ga, 75Br, 76Br, 77Br, 99mTc, 111In, 123I, 124I, 125I, or 131I; R2 represents either a hydrogen atom, or a substituent different from that represented by R1; and R3 represents any one of a bond, an alkylene group having 1 to 6 carbon atoms, and an oxyalkylene group having 1 to 6 carbon atoms.

Abstract: A method for oral administration of an active ingredient to a subject is provided whereby a plurality of bubbles containing the active ingredient t are formed in a small intestinal of the subject. The method includes administering orally to the subject an effective amount of the above-mentioned pharmaceutical composition. The pharmaceutical composition includes a drug layer and an enteric coating layer. The drug layer comprises an active ingredient, a surfactant, an acidic component and an effervescent ingredient. The active ingredient comprises a nucleic acid, a peptide or a protein. When the acidic component of the drug layer is dissolved in the small intestinal to react with the effervescent ingredient for generating carbon dioxide and the plurality of bubbles containing the active ingredient, and the active ingredient is embedded in a gap formed between an inner layer and an outer layer of an double-layer structure formed by the surfactant.

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.