Abstract: The present invention is in the therapeutic fields of drugs for medical conditions relating to diabetes. More specifically the invention relates to novel acylated derivatives of human insulin analogues. The invention also provides pharmaceutical compositions comprising such insulin derivatives, and relates to the use of such derivatives for the treatment or prevention of medical conditions relating to diabetes.

Abstract: The present invention relates to a liquid formulation of long-acting insulin conjugate, comprising a pharmaceutically effective amount of a long-acting insulin conjugate, wherein a physiologically active peptide, which is an insulin, is linked to an immunoglobulin Fc region; and an albumin-free stabilizer, wherein the stabilizer comprises a buffer, a sugar alcohol, a non-ionic surfactant, and an isotonic agent, and a method for preparing the formulation. For preventing microbial contamination in multiple uses, a preservative can be added to the formulation. The liquid formulation of the present invention does not comprise a human serum albumin and potentially hazardous factors to body, and thus it has excellent storage stability for insulin conjugate without a risk of viral infection.

Abstract: A process is described for purifying insulin and insulin analogs that comprises use of two or more orthogonal chromatographic purification steps in tandem following enzymatic digestion of the propeptide-insulin precursor to remove specific product impurities, improve process consistency, and increase process redundancy in the purification of the insulin or insulin analog, e.g., insulin lispro.

Abstract: The present invention is in the therapeutic fields of drugs for medical conditions relating to diabetes. More specifically the invention relates to novel acylated derivatives of human insulin analogues. The invention also provides pharmaceutical compositions comprising such insulin derivatives, and relates to the use of such derivatives for the treatment or prevention of medical conditions relating to diabetes.

Abstract: A method for maintaining the biological activity in a protein formulation without adding an antioxidant and for inhibiting the formation of insoluble particles, comprising adding to the protein formulation a poloxamer as a surfactant.

Abstract: A method for crystallizing insulin or insulin analogs under alkaline conditions and purifying the insulin or insulin analog crystals by filtering through a filter and drying the insulin or insulin analog crystals captured on the filter to produce crystalline insulin or insulin analog crystal compositions is described. In particular aspects, the method may be used to crystalize insulin glargine.

Abstract: Compositions and methods for modulating injection site pain associated with rapid acting injectable insulin formulations have been developed for subcutaneous injection. The formulations contain insulin in combination with a zinc chelator such as ethylenediaminetetraacetic acid (“EDTA”), a dissolution/stabilization agent such as citric acid, a magnesium salt, and, optionally, additional excipients. New presentations include rapid acting concentrated insulin formulations and a way to enhance the absorption of commercially available rapid acting analog formulations by mixing them with a vial containing dry powder excipients that accelerate their absorption. Devices for mixing excipient and insulin together at the time of administration, while minimizing residence time of the mixture, are also described.

Abstract: The present invention relates to the preparation of insulin compounds including their analogs or derivatives thereof from their corresponding precursor forms by a one step enzymatic reaction involving the combinatorial and concurrent use of optimal quantities of trypsin and carboxypeptidase B that work synergistically directing the reaction in a controlled manner to avoid production of random undesired byproducts. Particularly, the enzymatic conversion reactions of the instant invention offer advantages of reduction in the number operational steps, higher yield and purity of the desired end products.

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: The present invention relates to pharmaceutical composition containing nemorubicin hydrochloride incorporated in microspheres. The compositions are useful for chemoembolization, particularly for loco regional treatment of tumors.

Abstract: Pharmaceutical composition for parenteral administration comprising a basal insulin peptide and an insulinotropic GLP-1 peptide comprising at least 6 zinc atoms per 6 insulin molecules.

Abstract: Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of a disease or disorder, e.g., autoimmune disease, inflammatory disease, central nervous system disorder, cardiovascular disease, or metabolic disorder. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.

Abstract: Compositions and methods for modulating injection site pain associated with rapid acting injectable insulin formulations have been developed for subcutaneous injection. The formulations contain insulin in combination with a zinc chelator such as ethylenediaminetetraacetic acid (“EDTA”), a dissolution/stabilization agent such as citric acid, a magnesium salt, and, optionally, additional excipients. New presentations include rapid acting concentrated insulin formulations and a way to enhance the absorption of commercially available rapid acting analog formulations by mixing them with a vial containing dry powder excipients that accelerate their absorption. Devices for mixing excipient and insulin together at the time of administration, while minimizing residence time of the mixture, are also described.

Abstract: Stabilized pharmaceutical formulations of insulin analogues and/or insulin derivatives are disclosed.

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 pharmaceutical compositions containing such derivatives and to methods of treating diabetes and hyperglycaemia using the insulin derivatives of the invention.

Abstract: Compositions and methods for modulating injection site pain associated with rapid acting injectable insulin formulations have been developed for subcutaneous injection. The formulations contain insulin in combination with a zinc chelator such as ethylenediaminetetraacetic acid (“EDTA”), a dissolution/stabilization agent such as citric acid, a magnesium salt, and, optionally, additional excipients. New presentations include rapid acting concentrated insulin formulations and a way to enhance the absorption of commercially available rapid acting analog formulations by mixing them with a vial containing dry powder excipients that accelerate their absorption. Devices for mixing excipient and insulin together at the time of administration, while minimizing residence time of the mixture, are also described.

Abstract: The invention provides methods for improving the physical and chemical stabilities of therapeutic proteins in solutions by reducing or eliminating protein degradation, aggregation and precipitation using small molecule stabilizing agents such as proline, arginine and/or compounds capable of forming a Schiff bond with amino groups of the protein. The invention further provides liquid formulations of a monomeric insulin stabilized by one of more stabilizing agents such as proline, arginine and/or acetone. Also provided are methods of making and using the stabilized monomeric insulin formulations.

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

Abstract: Methods, compositions, systems, devices and kits are provided for preparing and using a multi-layer polymeric microstructure composition for delivering a therapeutic agent to a subject. In various embodiments, the therapeutic agent includes at least one selected from the group of: a drug, a protein, a sugar, a carbohydrate, and a nucleotide sequence. In related embodiments, the composition is a fiber, a suture, a sphere, an implant, or a scaffold.

Abstract: Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of a disease or disorder, e.g., autoimmune disease, inflammatory disease, central nervous system disorder, cardiovascular disease, or metabolic disorder. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.

Abstract: The invention provides compositions and methods for determining insulin resistance and/or pancreatic ?-cell dysfunction in a subject. The invention also provides compositions and methods for treating a subject according to the insulin resistance and/or pancreatic ?-cell dysfunction in the subject.

Abstract: A composition in the form of an injectable aqueous solution, the pH of which is between 6.0 and 8.0, includes at least a basal insulin, the isoelectric point pI of which is between 5.8 and 8.5; and a dextran substituted by radicals carrying carboxylate charges and hydrophobic radicals. Single-dose formulations at a pH of between 7 and 7.8 includes a basal insulin whose isoelectric point is between 5.8 and 8.5 and a prandial insulin.

Abstract: Protection of proteins against fibrillation may be afforded by introduction of certain histidine substitutions into the protein, such that a pair of histidines are present with sufficient spacing as to allow the histidines to coordinate with zinc. In the case of insulin, introduction of histidine residue substitutions at residues A4 and A8 together or a histidine residue substitution at residue B1, provides increased resistance to fibrillation while maintaining at least a majority of the activity of the insulin analogue. Introduction of a histidine residue substitution at residue A8 restores at least a portion of fibrillation resistance that may have been harmed by substitutions present on the B-chain such as those present in fast-acting insulins. Proteins protected by such histidine substitutions may be used to provide a pharmaceutical composition. A method of treating a patient includes administering a physiologically effective amount of the pharmaceutical composition to the patient.

Abstract: The present invention provides methods and materials by which glycosylation of glycoproteins can be regulated. Methods include the monitoring and regulation of parameters such that a glycoprotein having a desired product quality is obtained.

Abstract: The present invention is directed to compositions and methods of preparation of phospholipid depots that are injectable through a fine needle.

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

Abstract: The invention relates to a method for producing an aqueous, pharmaceutical formulation comprising an insulin, an insulin analog, or an insulin derivative, wherein the ready-made formulation takes place directly by dissolving the insulin, the insulin analog, or the insulin derivative as a solid in a suitable solvent mixture.

Abstract: The present invention relates to pharmaceutical formulations comprising insulin, an insulin analog, an insulin derivative, or a combination of any of the foregoing, and a salt of protamine, to methods of preparing such formulations, and to uses of such formulations in the treatment of diseases and conditions for which use of the insulin peptide(s) contained in such formulations is indicated. The present invention further relates to methods for increasing the stability and/or solubility of insulin in insulin-containing formulations at a pH less than 7.0 by adding a salt of protamine to the insulin-containing formulations.

Abstract: The present invention relates to a pharmaceutical composition comprising an insulin compound in a concentration that is sufficient to maintain a therapeutically effective level of the insulin compound in blood plasma for at least 3 days characterized by having a pharmacokinetic profile in vivo with substantially no burst of the insulin compound. The present invention further relates to the use of an insulin compound for preparing said pharmaceutical composition as well as a kit of parts comprising said pharmaceutical composition.

Abstract: Compositions and methods for modulating the pharmacokinetics and pharmacodynamics of rapid acting injectable insulin formulations are described herein. In the preferred embodiment, the formulations are administered via subcutaneous injection. The formulations contain insulin in combination with a zinc chelator such as ethylenediaminetetraacetic acid (“EDTA”) and a dissolution/stabilization agent, and optionally additional excipients. Calcium disodium EDTA is less likely to remove calcium from the body, and typically has less pain on injection in the subcutaneous tissue. Modulating the type and quantity of EDTA can change the insulin absorption profile. Increasing the quantity of citrate can further enhance absorption and chemically stabilize the formulation. In the preferred embodiment, the formulation contains human insulin, calcium disodium EDTA and a dissolution/stabilization agent such as citric acid or sodium citrate.

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

Abstract: Systems and methods using a database of physiological information for the design, development, testing and use of therapeutics. In one aspect, the physiological information can include at least one of: hemodynamic monitoring information, pulmonary arterial pressure, cardiac output, heart rate, respiratory rate, peripheral vascular resistance, total peripheral resistance or dicrotic notch information. Optionally, the cardiovascular physiology information can include ambulatory physiological information.

Abstract: The invention claims a process for making an insulin-oligomer conjugate IN-105. IN-105 precursor having formula G-A-V-R-[B-Chain]-R-D-A-D-D-R-[A-Chain] is cloned and expressed in Pichia. The biosynthetic precursor is then conjugated with an activated oligomer. The IN-105 precursor-oligomer conjugate is then treated with protease and purified to afford active insulin-oligomer conjugate of formula insulin-OC—CH2—CH2—(OCH2CH2)3—OCH3.

Abstract: The present invention relates to a new composition comprising substances that promote DNA repair, reduce body fat levels and increase lean body mass and that decrease wrinkle appearance and/or improvement in skin surface. In some aspects, the composition of the present invention include resveratrol, forskohlin and astaxanthin. In another aspect the composition of the present invention further comprises carboxy alkyl ester. The present invention also relates to a method of promoting internal health and external appearance in a subject in need, said method comprising administering to the subject a composition that promotes DNA repair, reduces body fat levels and increases lean body mass and that decreases wrinkle appearance and/or improvement in skin surface.

Abstract: An insulin compound coupled to a modifying moiety having a formula: —X—R1—Y—PAG-Z—R2??(Formula VI) where, X, Y and Z are independently selected linking groups and each is optionally present, and X, when present, is coupled to the insulin compound by a covalent bond, either R1 or R2 is a lower alkyl, optionally including a carbonyl group, and when R1 is a lower alkyl, R2 is a capping group, and PAG is a linear or branched carbon chain incorporating one or more alkalene glycol moieties, and optionally incorporating one or more additional moieties selected from the group consisting of —S—, —O—, —N—, and —C(O)—.

Abstract: An insulin compound coupled to a modifying moiety having a formula: —X—R1—Y-PAG-Z—R2 ??(Formula VI) where, X, Y and Z are independently selected linking groups and each is optionally present, and X, when present, is coupled to the insulin compound by a covalent bond, either R1 or R2 is is a lower alkyl, optionally including a carbonyl group, and when R1 is a lower alkyl, R2 is a capping group, and PAG is a linear or branched carbon chain incorporating one or more alkalene glycol moieties, and optionally incorporating one or more additional moieties selected from the group consisting of —S—, —O—, —N—, and —C(O)—.

Abstract: The invention relates to novel insulin analogs having a basal time-action profile, which are characterized by the following features: a) the B chain end consists of an amidated basic amino acid residue such as lysine or arginine amide; b) the N-terminal amino acid residue of the insulin A chain is a lysine or arginine radical; c) the amino acid position A8 is occupied by a histidine radical; d) the amino acid position A21 is occupied by a glycine radical; and e) one or more substitutions and/or additions of negatively charged amino acid residues are carried out in the positions A5, A15, A18, B-1, B0, B1, B2, B3 and B4.

Abstract: This invention is a method of using a class of excipients for protein formulation to reduce and/or eliminate protein aggregation in solutions or solids. This class of compounds contains carbonyl group(s) to form Schiff base(s) with amino groups of proteins and also contains moieties to keep protein molecules spatially separated. This method has never been disclosed anywhere in the literature.

Abstract: Erythrocyte ATP-release modulators and composition and methods for their use to potentiate serum glucose clearance and vasodilation; methods for prophylactic or palliative therapy of glucose processing or vascular disorders; processes for preparing the modulators and compositions comprising them; and kits therefor.