Abstract: The invention discloses a polymer micro-needle array chip, comprising a substrate and a micro-needle array standing thereon; the material for preparing the micro-needle array is a polyacrylamides polymer, with the molecular weight of 1.0×104-2.0×105, the Vickers hardness of 150-600 HV, and the impact strength of 5-30 J/m. The polymer micro-needle array chip has a high mechanical strength and a sharp needle tip, and it can easily dissolve or swell on contact with a water-containing environment, which helps the drug to be released slowly in the skin.

Abstract: Single chain insulin analogs are provided having high potency and specificity for the insulin receptor. As disclosed herein optimally sized linking moieties can be used to link human insulin A and B chains, or analogs or derivatives thereof, wherein the carboxy terminus of the B25 amino acid of the B chain is linked to the amino terminus of the A1 amino acid of the A chain via the intervening linking moiety. In on embodiment the linking moiety comprises a polyethylene glycol of 6-16 monomer units and in an alternative embodiment the linking moiety comprises a non-native amino acid sequence derived form the IGF-1 C-peptide and comprising at least 8 amino acids and no more than 12 amino acid in length. Also disclosed are prodrug and conjugate derivatives of the single chain insulin analogs.

Abstract: A supramolecular insulin assembly and supramolecular exendin-4 assembly, which is useful as a protein therapeutic agent for the treatment of metabolic disorders particularly diabetes. The supramolecular assemblies disclosed in the present invention consists of insoluble and aggregated oligomers the protein. The invention also provides pharmaceutical compositions comprising the supramolecular assembly.

Abstract: The present disclosure provides a cross-linked material comprising conjugates which include two or more separate affinity ligands bound to a non-polymeric framework, wherein the molecular weight of the non-polymeric framework is less than 10,000 Da; and multivalent cross-linking agents that non-covalently bind the affinity ligands of the conjugates and thereby cross-link the conjugates to form a cross-linked material, wherein the non-covalent bonds between the multivalent cross-linking agents and the affinity ligands are competitively dissociated in the presence of excess amounts of a target molecule. The present disclosure also provides methods of making and methods of using these materials. In other aspects, the present disclosure provides exemplary conjugates including conjugates for use in glucose responsive cross-linked materials.

Abstract: The present invention relates to methods of diagnosing a kidney disorder in a patient, as well as methods of monitoring the progression of a kidney disorder and/or methods of monitoring a treatment protocol of a therapeutic agent or a therapeutic regimen. The invention also relates to assay methods used in connection with the diagnostic methods described herein.

Abstract: A glucose binding amphiphilic peptide hydrogel insulin delivery system that is responsive to glucose concentrations under physiological conditions is provided. Insulin is encapsulated in a glucose binding hydrogel, made from self-assembling amphiphilic peptides including a hydrophobic domain including a beta sheet forming region coupled to a charged hydrophilic domain modified to contain a glucose binding segment. The formulations are designed to release insulin as a function of blood glucose level, maintaining the patients' blood glucose level in an optimum range and avoiding both hyper- and hypoglycemia.

Abstract: Compositions and methods for the detection and treatment of T1D are provided.

Abstract: The embodiments herein provide a long-acting injectable drug (insulin) delivery nano-carrier system and a method of synthesising the same. The insulin entrapped nanoparticles are prepared using a lipid/phospholipid core which is coated by a polymer. The lipid and phospholipid are dissolved in organic solvent. This solution is transferred into an aqueous phase consisting of distilled water or a buffer and dissolved insulin. A solution of polymer is added drop wise. The drug entrapped nanoparticle formation is achieved by diffusion of the organic solvent within the aqueous solvent to obtain the nanoparticles. The drug gets entrapped within the formed nanoparticles via the anti-solvency effect of the aqueous matrix. The resulting drug nanocarriers are capable of releasing the drug in a slow rate upon injection. The synthesized drug carrying nanoparticles are cryopreserved stored for future administration. For better storage the nanodispersion is dried to form a powder.

Abstract: In certain embodiments compositions are provided that comprise a pentapeptide comprising the formula: C1-X2-X3-X4-C5 where C1 and C5 are independently selected cysteines or cysteine analogues, or other amino acids with sidechains suitable for cyclization, where the cysteines or cysteine analogs are attached to each other by a linkage that does not comprise X2, X3, and X4; where X2, X3, and X4 are independently selected amino acids; and the peptide, when administered to a cell alters APP signaling and/or switches APP processing from aberrant to normal. The compositions mitigate amyloid plaque formation.

Abstract: Injectable insulin formulations with improved stability and rapid onset of action are described herein. The formulations may be for subcutaneous, intradermal or intramuscular administration. In the preferred embodiment, the formulations are administered via subcutaneous injection. The formulations contain insulin in combination with a chelator and dissolution agent, and optionally additional excipients. In the preferred embodiment, the formulation contains human insulin, a zinc chelator such as EDTA and a dissolution agent such as citric acid. These formulations are rapidly absorbed into the blood stream when administered by subcutaneous injection. In the preferred embodiment, the insulin is provided as a dry powder in a sterile vial. This is mixed with a diluent containing a pharmaceutically acceptable carrier, such as water, a zinc chelator such as EDTA and a dissolution agent such as citric acid shortly before or at the time of administration.

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: The present invention relates to novel human insulin derivatives which are soluble at physiological pH values and have a prolonged profile of action. The invention also relates to methods of providing such derivatives, to pharmaceutical compositions containing them, to methods of treating diabetes and hyperglycaemia using the insulin derivatives of the invention and to the use of such insulin derivatives in the treatment of diabetes and hyperglycaemia.

Abstract: A method for preventing cognitive decline, comprises the steps of identifying, in an individual, a first stage of cognitive decline corresponding to Subjective Cognitive Impairment and administering a predetermined treatment to the individual to inhibit a progression of the individual to a second predetermined stage of cognitive decline or to inhibit progression of cognitive decline within the first stage.

Abstract: The present invention provides a pharmaceutical composition for the sustained release of C-peptide. The composition is in the form of a gel containing C-peptide. The gel formation is achieved by the adjustment of pH of the composition and/or by addition of divalent metal ions. The composition does not include any other gel-forming agents. Methods for producing the composition, medical uses of the composition and products containing two or more gel compositions as a combined preparation are also encompassed.

Abstract: Oral insulin formulations and processes for preparing oral insulin formulations are provided.

Abstract: The present invention relates to compositions and methods for transdermal drug delivery comprising formulating a phosphatidylcholine carrier composition containing the drug and applying the composition to the skin.

Abstract: Provided is a method of stimulating collagen synthesis and proteoglycan (lumican and keratocan) accumulation. Collagenase isolated keratocytes were cultured with or without insulin with or without ascorbate. Insulin stimulates the synthesis of collagen but does not affect the accumulation of lumican and keratocan. Insulin plus ascorbate, however, stimulates the synthesis of collagen and increased the accumulation of these proteoglycans. The accumulation of PGDS, a KSPG that does not interact with collagen, is not affected by ascorbate. Only the collagen made in the presence of ascorbate was pepsin resistant. EDB overrode the effects of ascorbate on pepsin resistance and proteoglycan accumulation.

Abstract: An insulin analogue comprises a B-chain polypeptide incorporating a halogenated phenylalanine at position B24, B25 or B26. The halogenated phenylalanine may be ortho-monofluoro-phenylalanine, ortho-monobromo-phenylalanine, ortho-monochloro-phenylalanine, or para-monochloro-phenylalanine. The analogue may be of a mammalian insulin, such as human insulin. A nucleic acid encodes such an insulin analogue. The halogenated insulin analogues retain significant activity. A method of treating a patient comprises administering a physiologically effective amount of the insulin analogue or a physiologically acceptable salt thereof to a patient. Halogen substitution-based stabilization of insulin may enhance the treatment of diabetes mellitus in regions of the developing world lacking refrigeration.

Abstract: Provided herein are methods and compositions for oral administration of therapeutic proteins, improved protease inhibitor preparations, methods for producing same, and compositions comprising same.

Abstract: The invention relates to a composition in aqueous solution, including insulin and at least one substituted anionic compound chosen from substituted anionic compounds consisting of a backbone formed from a discrete number u of between 1 and 8 (1?u?8) of identical or different saccharide units, linked via identical or different glycoside bonds, said saccharide units being chosen from the group consisting of hexoses, in cyclic form or in open reduced form, said compound comprising partially substituted carboxyl functional groups, the unsubstituted carboxyl functional groups being saliflable. The invention also relates to a pharmaceutical formulation comprising a composition as claimed in any one of the preceding claims.

Abstract: The invention provides novel compositions of bioactive polypeptides and proteins with improved stability and shelf-life. The compositions are based on liquid vehicles selected from semifluorinated alkanes. These vehicles are remarkably effective in protecting polypeptides and proteins from degradation and/or aggregation. The compositions are useful for topical administration, e.g. into an eye, or by parenteral injection, e.g. via the subcutaneous or intramuscular route.

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 disclosure provides crystalline insulin-conjugates. The present disclosure also provides formulations, methods of treatment, methods of administering, and methods of making that encompass these crystalline insulin-conjugates.

Abstract: Lipidated micro- or macroparticles are prepared by covalently linking a glycoprotein, typically collagen, with at least one lipid. An amino group in the glycoprotein is joined with a primary amine in the lipid. These particles can be used to encapsulate active ingredients, such as drugs.

Abstract: The present invention relates to a method for the quantitative determination of an impurity present in a peptide product, wherein the impurity cannot be separated from other impurities or the main product. The method particularly involves the use of high resolution mass spectrometry (MS) detection with or without high performance liquid chromatography (HPLC). The method can be used for the investigation of the quality of peptides and proteins, particularly of pharmaceutical peptides and proteins.

Abstract: The present invention relates to shelf stable non-aqueous pharmaceutical compositions, and to the use thereof in methods of treating diabetes and hyperglycaemia.

Abstract: Disclosed is a formulation for parenteral administration comprising insulin that comprises a pH memory between 1 to 4 or between 6 to 8 and an aprotic polar solvent, wherein the insulin is solubilized in the aprotic polar solvent, wherein the solubilized insulin comprises stable monomeric or dimeric forms of insulin or mixtures thereof, and wherein the water content of the formulation is equal to or less than 15% w/v.

Abstract: Gastroretentive controlled release vehicles may, in some embodiments, (1) comprise a polymeric matrix and agents for the treatment, prevention, and/or mitigation of a disease and/or side effect thereof and (2) have both gastroretentive properties and controlled release properties. Preferrably, the polymeric matrix may comprise ethylene copolymers, ethyl celluloses, and/or thermoplastic polyurethanes that may optionally be partially crosslinked.

Abstract: The present invention relates to insulin derivatives which are naturally occurring insulins or analogues thereof which have a side chain attached either to the ?-amino group of the N-terminal amino acid residue of the B chain or to the ?-amino group of a Lys residue present in the B chain of the parent insulin, the side chain being of the general formula: —W—X—Y—Z wherein W, X, Y and Z are as defined in the disclosure.

Abstract: A method for nasal administration of a pharmaceutical composition comprising a hydrophilic bioactive substance and any one of (a) to (c): (a) a peptide having the amino acid sequence shown in SEQ ID NO:1; (b) a peptide having the same amino acid sequence as shown in SEQ ID NO:1 except that one or several amino acids are deleted, substituted and/or added, the peptide having nasal mucosal permeability; (c) a peptide having an amino acid sequence represented by the reverse sequence of (a) or (b), the peptide having nasal mucosal permeability, with the proviso that a C-terminal amidated peptide is excluded. A hydrophilic bioactive substance having a low transmucosal absorption capability which has conventionally been able to be administered by only injection can be nasally administered. Such a pharmaceutical composition is useful for improvement of the pain and the inconvenience of patients caused by administration by injection.

Abstract: The present invention is based, at least in part, on the identification of a pharmaceutical container formed, at least in part, of a glass composition which exhibits a reduced propensity to delaminate, i.e., a reduced propensity to shed glass particulates. As a result, the presently claimed containers are particularly suited for storage of pharmaceutical compositions and, specifically, a pharmaceutical solution comprising a pharmaceutically active ingredient, for example, Victoza (liraglutide), Tresiba (insulin degludec), Ryzodeg (insulin degludec/insulin aspart), IDegLira (liraglutide and insulin degludec), NovoSeven (recombinant human coagulation factor VIIa), NovoSeven RT (recombinant human coagulation factor VIIa), or Turoctocog alfa (third-generation recombinant coagulation factor VIII).

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 covalently linked affinity ligand which is capable of competing with glucose for binding with at least one of said binding sites; 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: Methods for the treatment of a cell proliferation disorder in a subject, involving: (1) administering to the subject at least one activatable pharmaceutical agent that is capable of effecting a predetermined cellular change when activated, either alone or in combination with at least one energy modulation agent; and (2) applying an initiation energy from an initiation energy source to the subject, wherein the applying activates the activatable agent in situ, thus causing the predetermined cellular change to occur, wherein the predetermined cellular change treats the cell proliferation disorder, preferably by causing an increase or decrease in rate of cell proliferation, and a kit for performing the method, a computer implemented system for performing the method, a pharmaceutical composition useful in the method and a method for causing an autovaccine effect in a subject using the method.

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: 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: Methods and devices for delivering variable amounts of a drug formulation directly from a drug delivery device without requiring point of use reconstitution as a separate mixing step are described herein. These methods and devices increase the convenience, speed and simplicity of administration of drug formulations. The devices mix two or more components in a constant mixing ratio effectively simultaneous to administration, and allow for variable doses while retaining the desired ratio of the components in each dose. The devices are particularly useful for administering drug formulations that are unstable at room temperature in liquid form. The methods described herein generally use conventional devices that have been modified to administer an unstable compound and provide acceptable storage stability. Typical devices include infusion sets, pump reservoirs, syringes, pens, vials and cartridges.

Abstract: Compositions containing a therapeutic peptide covalently linked to Vitamin B12 at the 5?-hydroxyl group of the ribose moiety of ?-ligand are described. The length of the linkage is optimized so that the biological activity of both the Vitamin B12 and the therapeutic peptide is maintained. Therapeutic peptide includes insulin, PYY, NPY and GLP-1. Attachment to Vitamin B12 provides uptake of the therapeutic peptide from the digestive tract and longer residence time.

Abstract: Pharmaceutical compositions and methods for delivering a polypeptide to the central nervous system of a mammal via intranasal administration are provided. The polypeptide can be a catalytically active protein or an antibody, antibody fragment or antibody fragment fusion protein. The polypeptides are formulated with one or more specific agents.

Abstract: The present invention is related to single-chain insulin having insulin activity comprising a B- and an A-chain or a modified B- and A-chain connected by a connecting peptide of from 6-11 amino acids. The single-chain insulins will have biological insulin activity and an IGF-1 receptor affinity similar to or lower than that of human insulin and a high physical stability. The single-chain insulin may contain at least one basic amino acid residues in the connecting peptide. The single-chain insulins may also be acylated in one or more Lys residues.

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

Abstract: The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating or preventing diseases, disorders or conditions related to diabetes mellitus using albumin fusion proteins of the invention.

Abstract: The invention describes a non-aqueous liquid pharmaceutical composition comprising at least one lipid and at least one insulin. Also described is a method of producing a pharmaceutical composition comprising a lipid and a method of purifying a lipid, a cosolvent, a surfactant or a pharmaceutical composition comprising a lipid.

Abstract: The present invention provides a human insulin analogue, an acylated derivative thereof and a physiologically acceptable salt. The present invention further provides a preparation method for the insulin analogue and an application of the insulin analogue as a therapeutic agent, and particularly as a diabetes mellitus therapeutic agent.

Abstract: Methods, compositions and devices utilizing stinging cells/capsules for conditioning a tissue prior to delivery of a pharmaceutical agent are described.

Abstract: The subject matter of this invention is directed towards chemically and thermodynamically stable single-chain insulin (SCI) analogues that are resistant to deamidation and fibrillation. The invention further discloses improved methods for the recombinant expression, purification and refolding of SCI.

Abstract: The invention is related to novel N-terminally modified insulin derivatives, pharmaceutical compositions comprising such and methods of making such.

Abstract: If albumin is added to a pharmaceutical formulation containing acylated insulin described in WO 2009/022005 and WO 2009/022013, the acylated insulin can be kept in solution after subcutaneous injection.

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: The present invention is related to insulin derivatives having a side chain attached either to the ?-amino group of the N-terminal amino acid residue of B chain or to an ?-amino group of a Lys residue present in the B chain of the parent insulin molecule via an amide bond which side chain comprises one or more residues of ethyleneglycol, propyleneglycol and/or butyleneglycol containing independently at each termini a group selected from —NH2 and —COOH; a fatty diacid moiety with 4 to 22 carbon atoms, at least one free carboxylic acid group or a group which is negatively charged at neutral pH; and possible linkers which link the individual components in the side chain together via amide or ether bonds, said linkers optionally comprising a free carboxylic acid group.

Abstract: The invention relates to a pharmaceutical formulation for sustained delivery of a therapeutic agent, preferably a protein, polypeptide, an antibody or an antibody fragment, comprising one or more gel forming peptides wherein the formulation exhibits sustained delivery for at least two weeks, three weeks, four weeks, five weeks, six weeks, seven weeks, eight weeks, nine weeks, ten weeks, eleven weeks, twelve weeks or more. In one embodiment, the invention relates to a formulation comprising self-assembling peptides that undergo sol-gel transition in the presence of an electrolyte solution such as biological fluids and salts. The formulation can provide sustained release of antibody and antibody fragments, in particular, IgG. Antibody diffusivities can be decreased with increasing hydrogel nanofiber density, providing a means to control the release kinetics.