Abstract: New biosynthetic analogues of recombined human insulin of prolonged therapeutical activity, which can find place in prophylactic and treatment of diabetes.

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: The present invention relates to exendin-4 peptide analogues and their medical use, for example in the treatment of disorders of the metabolic syndrome, including diabetes and obesity, as well as reduction of excess food intake.

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: Provided are an insulin-lipid complex, a preparation method thereof, and a formulation thereof. The insulin-lipid complex is prepared by compounding insulin and a lipid material in an organic solvent system containing a low boiling point acid, and drying. The mass ratio of insulin to the lipid material is 1:3˜1:20. An oil solution of the insulin-lipid complex and vesicles containing insulin are further provided.

Abstract: The invention provides an apparatus for forming fine particles of a substance in a precipitation chamber, in which the apparatus has means to convey the fine particles from the precipitation chamber to at least one particle collection chamber, downstream of the precipitation chamber, the particle collection chamber having an inlet and an outlet separate from the inlet. The invention also provides a method of forming fine particles of a substance, the method comprising contacting a non-gaseous fluid containing the substance with a dense fluid to expand the non-gaseous fluid in a precipitation chamber, conveying a resulting mixture of fluid and the fine particles from the precipitation chamber to a collection chamber, the collection chamber having an inlet and an outlet separate from the inlet.

Abstract: A method of delivering a drug composition comprises providing a carrier having a phosphatidylcholine component and a drug entrapped therein, and applying the composition to the skin for transdermal delivery of the drug, wherein the composition is stable at room temperature.

Abstract: A method of delivering a drug composition comprises providing a carrier having a phosphatidylcholine component and a drug entrapped therein, and applying the composition to the skin for transdermal delivery of the drug, wherein the composition is stable at room temperature.

Abstract: A method of delivering a drug composition comprises providing a carrier having a phosphatidylcholine component and a drug entrapped therein, and applying the composition to the skin for transdermal delivery of the drug, wherein the composition is stable at room temperature.

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: The invention relates to novel insulin analogs having a basal time-action profile, which are characterized by the addition and/or substitution of negatively and positively charged amino acid residues and by an amidation of the C-terminal carboxy group of the B chain and histidine in position 8 of the insulin A chain. The invention also relates to the production and use thereof.

Abstract: In one aspect, the disclosure provides cross-linked materials that include multivalent polynucleotide aptamers that bind a 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 target molecule for binding with the aptamers and wherein conjugates are cross-linked within the material as a result of non-covalent interactions between aptamers and affinity ligands on different conjugates. These materials are designed to release amounts of conjugate in response to desired concentrations of the target molecule. Depending on the end application, in various embodiments, the conjugates may also include a drug and/or a detectable label. The drug, detectable label and affinity ligands may be covalently or non-covalently bound to the conjugate framework.

Abstract: The invention relates to a composition for use as a medicament comprising insulin in combination with at least one compound of formula (I) wherein the radicals R1 to R6 have the meaning according to claim 1, and/or physiologically acceptable salts thereof. Another object of the invention concerns a pharmaceutical composition comprising as active ingredients effective amounts of insulin and at least one compound of formula (I), together with pharmaceutically tolerable adjuvants, for the prophylactic or therapeutic treatment and/or monitoring of physiological and/or pathological conditions that are associated with insulin resistance. The invention also relates to a pharmaceutical package comprising insulin in a first dosage unit and at least one compound of formula (I) in a second dosage unit.

Abstract: Provided are orally administrable thin film dosage forms adapted to adhere to a mucosal tissue of a patient, wherein said film comprises mixtures of polymers and insulin.

Abstract: Disclosed are PEG-modified Exendin-4 analogs and uses thereof. In particular, disclosed are PEG-modified Exendin-4 analogs as shown in formula (I), i.e., PEG-M-X-(Ex-4), or pharmaceutically acceptable salts thereof, as well as Exendin-4 analogs as shown in formula (II), i.e., [Aap]Exendin-4, wherein the symbols are as defined in the specification. Further disclosed are methods for preparing PEG-modified Exendin-4 analogs, uses of PEG-modified Exendin-4 analogs, compositions comprising the same, as well as use of the Exendin-4 analogs in the preparation of the PEG-modified Exendin-4 analogs. In the PEG-modified Exendin-4 analogs, modification by polyethylene glycol occurs in a site-directed manner in the peptide chains of the Exendin-4 analogs. The PEG-modified Exendin-4 analogs can be used to prevent and/or treat diseases and/or symptoms related to decreased activity of GLP-1 receptors, such as type II diabetes.

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: The present invention relates to crystalline polymorphic forms of the di-sodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic acid, pharmaceutical compositions containing the same, methods of preparing the same, and methods for facilitating the delivery of active agents with the same.

Abstract: Methods are provided for drying a particle. Specifically, there is provided a spray-dried diketopiperazine-insulin particle formulation having improved aerodynamic performance and in which the active agent is more stabile and efficiently delivered as compared to that of the lyophilized diketopiperazine-insulin formulation. The dry powders have utility as pharmaceutical formulations for pulmonary delivery.

Abstract: An insulin-gold nanocluster, a pharmaceutical composition for treating diabetes comprising the insulin-gold nanocluster, and a method for detecting adipose cells in a tissue by using the insulin-gold nanocluster are provided. Herein, the insulin-gold nanocluster of the present invention comprises: a gold nanocluster, and insulin connecting to the gold nanocluster, wherein the insulin-gold nanocluster emits red fluorescence at maximized wavelength of 670 nm.

Abstract: A container and method for storing a pharmaceutical agent are provided for enhancing the storage time. The storage time of the pharmaceutical agent is improved by reducing the loss of stabilizing agents in the pharmaceutical agent. The storage container is formed from a polyolefin that includes a stabilizing agent in an amount effective to reduce or inhibit the migration of stabilizing agents in the pharmaceutical agent. The polyolefin container is formed with a fatty acid amide such as erucamide for stabilizing insulin that contains m-cresol and/or phenol as stabilizing agents for the insulin. The fatty acid amide incorporated in the container inhibits and/or reduces the rate of migration of the m-cresol and/or phenol into the polyolefin to extend the storage life of the insulin. The container can be a syringe, such as a pre-filled syringe, a storage vial or the flow path of an infusion pump.

Abstract: Compositions for nasal administration, which comprise a pharmaceutical, a physiologically active peptide, or a peptide-related compound, and as the carrier thereof, crystalline cellulose with a specific particle diameter and/or partially pregelatinized starch are provided. Such compositions improve the in vivo absorption efficiency of pharmaceuticals.

Abstract: In one aspect, the disclosure provides a conjugate comprising an insulin molecule having an A-chain and a B-chain; an affinity ligand covalently bound to the A-chain; and a monovalent glucose binding agent covalently bound to the B-chain, wherein the affinity ligand competes with glucose for non-covalent binding with the monovalent glucose binding agent. In the absence of glucose, the monovalent glucose binding agent binds the affinity ligand to produce a “closed” inactive form of the insulin molecule. When free glucose is added, it competes with the affinity ligand for binding with the monovalent glucose binding agent to produce an “open” active form of the insulin molecule. The monovalent glucose binding agent and affinity ligand are covalently bound to the insulin molecule. The disclosure also provides methods of using these conjugates and methods of making these conjugates. In another aspect, the disclosure provides exemplary conjugates.

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: Insulin preparations comprising an insulin compound or a mixture of two or more insulin compounds, a nicotinic compound and an amino acid.

Abstract: Self-assembled gel compositions including a gelator, e.g., an enzyme-cleavable gelator, e.g., having a molecular weight of 2500 or less, are described. The self-assembled gel compositions can encapsulate one or more agents. Methods of making the self-assembled gel compositions, and methods of drug delivery using the self-assembled gel compositions are also described.

Abstract: Fatty acid compositions for administration of of pharmaceutical agents, such as proteins and peptides, protein and peptide conjugates, and/or cation-polypeptide conjugate complexes. In particular, the invention provides a solid pharmaceutical composition formulated for oral administration by ingestion, having from about 0.1 to about 75% w/w fatty acid component, where the fatty acid component comprises saturated or unsaturated C4, C5, C6, C7, C8, C9, C10, C11, or C12 fatty acids and/or salts of such fatty acids; and a therapeutic agent. Further, the invention provides a liquid pharmaceutical composition formulated for oral administration by ingestion, comprising: from about 0.1 to about 10% w/v fatty acid component, where the fatty acid component comprises saturated or unsaturated C4, C5, C6, C7, C8, C9, C10, C11, or C12 fatty acids and/or salts of such fatty acids; and a therapeutic agent.

Abstract: An apparatus and method for automatically supplying insulin based on exercise amount are provided. The apparatus includes a blood sugar measurer for measuring a blood sugar level of a patient; a controller for, comparing the measured blood sugar level with a predetermined blood sugar level, if the measured blood sugar level is greater than or equal to the predetermined blood sugar level, determining whether a current time is within a blood sugar change time zone, if the measured blood sugar level is equal to or higher than the predetermined blood sugar level, and if the current time does is not within the blood sugar change time zone, acquiring exercise amount information about the patient and determining a dose of insulin to be injected inject into the patient based on the acquired exercise amount information, if the current time does not fall within the blood sugar change time zone; and an insulin injector for injecting the determined dose of insulin into the patient.

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: Provided herein is a topical wound dressing that comprises a collagen and a flexible paste. Also provided is a wound dressing with a first layer of a sterilized mixture of collagen and a second adhesive layer effective to adhere to surrounding skin and to keep the first layer in contact with the wound. In addition there is provided a wound dressing foil that comprises collagen and a plastic compound that can provide a foil shape. Furthermore, methods of dressing wounds utilizing the wound dressings and wound dressing foil are provided herein.

Abstract: A method was developed to prepare silk fibroin microspheres using lipid vesicles as templates to efficiently load therapeutic agents in active form for controlled release. The lipids are subsequently removed through the use of a dehydration agent, such as methanol or sodium chloride, resulting in ?-sheet structure dominant silk microsphere structures having about 2 ?m in diameter. The therapeutic agent can be entrapped in the silk microspheres and used in pharmaceutical formulations for controlled-release treatments.

Abstract: The present invention provides a liquid composition, as an ejection liquid used for stably ejecting liquid droplets, including at least one kind of a protein and a peptide, and a compound having a betaine skeleton by application of thermal energy to the liquid; a method of making droplets form the liquid; and an ejection method and an ejection device suitable for utilizing protein liquid droplets. By adding a compound having a betaine skeleton to an aqueous solution of at least one kind of a protein and a peptide, the liquid composition is improved in stability for ejection by application of thermal energy. Further, a surfactant may be further added to the liquid composition containing the compound having a betaine skeleton, and in this case the effect of stable ejection can be obtained.

Abstract: A composition in aqueous solution, including an insulin and at least one oligosaccharide whose average degree of polymerization is between 3 and 13 and whose polydispersity index PDI is above 1.0, the oligosaccharide having partially substituted carboxyl functional groups, the unsubstituted carboxyl functional groups being salifiable.

Abstract: A sustained-release drug composition consisting essentially of microparticles of hyaluronic acid having a high molecular weight or an inorganic salt thereof and a protein or peptide drug encased in said microparticles, wherein the average size of said microparticles ranges from 0.1 to 40 ?m.

Abstract: Described are methods of improving glycemic control/improving insulin sensitivity by administering an inhibitor of serum response factor (SRF) activity, and methods of identifying new compounds for use in the described methods of treatment.

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: An insulin-gold nanocluster, a pharmaceutical composition for treating diabetes comprising the insulin-gold nanocluster, and a method for detecting adipose cells in a tissue by using the insulin-gold nanocluster are provided. Herein, the insulin-gold nanocluster of the present invention comprises: a gold nanocluster, and insulin connecting to the gold nanocluster, wherein the insulin-gold nanocluster emits red fluorescence at maximized wavelength of 670 nm.

Abstract: Methods are provided for drying a particle. Specifically, there is provided a spray-dried diketopiperazine-insulin particle formulation having improved aerodynamic performance and in which the active agent is more stabile and efficiently delivered as compared to that of the lyophilized diketopiperazine-insulin formulation. The dry powders have utility as pharmaceutical formulations for pulmonary delivery.

Abstract: Lis-Pro modified proinsulin sequences that have a modified C-peptide amino acid and/or nucleic acid modification are presented. Methods for producing Lis-Pro insulin analogs are also disclosed. Highly efficient processes for preparing the Lis-Pro insulin analogs and improved preparations containing the Lis-Pro insulin analogs prepared according to the methods described herein are also provided.

Abstract: Therapeutic peptide compositions comprise a therapeutic peptide, such as insulin, together with an alkyl N,N-disubstituted amino acetate, such as dodecyl 2-(N,N-dimethylamino) propionate.

Abstract: A Gantrez hydrogel comprising sodium, calcium, zinc, strontium, and ferric cations, and a polyvinylpyrrolidone based tack agent is disclosed. A method for preparation of the Gantrez hydrogel is also disclosed.

Abstract: Human proIslet Peptides (HIP) and HIP analogs and derivatives thereof, derived from or homologous in sequence to the human REG3A protein, chromosome 2p12, are able to induce islet neogenesis from endogenous pancreatic progenitor cells. Human proIslet Peptides are used either alone or in combination with other pharmaceuticals in the treatment of type 1 and type 2 diabetes and other pathologies related to aberrant glucose, carbohydrate, and/or lipid metabolism, insulin resistance, overweight, obesity, polycystic ovarian syndrome, eating disorders and the metabolic syndrome.

Abstract: Compositions and methods for modulating the deposition of elastin by administering compositions including insulin receptor agonists are described herein.

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 therapetuic 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 composition in the form of an injectable aqueous solution, the pH of which is between 6.0 and 8.0, including at least (a) a basal insulin, the isoelectric point pI of which is between 5.8 and 8.5; and (b) a co-polyamino acid bearing carboxylate charges and substituted with hydrophobic radicals. In one embodiment, the compositions also include a prandial insulin and/or a gut hormone.

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

Abstract: The invention relates to a method for treating type 2 diabetes patients, wherein insulin glargine is administered to the patient in an amount clinically tested to be safe and effective, wherein the type 2 diabetes is early type 2 diabetes, more particularly, wherein the insulin glargine is used as first-line drug.

Abstract: A composition for oral delivery of a poorly absorbed drug is disclosed. The composition includes the drug, an enhancer for increasing absorption of the drug through the intestinal mucosa, a promoter, which further increases the absorption of the drug in the presence of the enhancer, and optionally a protector for protecting the drug from physical or chemical decomposition or inactivation in the gastrointestinal tract. Illustrative enhancers include sucrose fatty acid esters, and illustrative promoters include aminosugars and amino acid derivatives, such as poly(amino acids). Illustrative protectors include methylcellulose, poly(vinyl alcohol), and poly(vinyl pyrrolidone).

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

Abstract: A sterile pharmaceutical composition for parenteral administration of propofol, said composition comprising propofol, optionally albumin, and less than about 10% by weight solvent for propofol, wherein said composition is stored in a container having a closure wherein said closure is inert to propofol.

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.