88 results about "Glucose responsive" patented technology

The invention relates to compositions and methods for the administration of therapeutic and / or diagnostic agents such as polypeptides to a mammal, and in particular, compositions suitable for oral administration. The invention provides polymeric particles, and in particular, nano / microparticles such as, but not limited to, microspheres and nanospheres, as well as methods of synthesizing them. The invention also provides methods of increasing the serum concentration of a therapeutic agent such as a polypeptide by orally administering polymeric particles comprising the therapeutic agent. The compositions of the invention allow the absorption of polypeptides through intestinal mucosa and intestinal cells and into the bloodstream of a mammal. The invention further provides a method of treating type II diabetes through the oral administration of compositions comprising insulin and also provides a related glucose-responsive insulin delivery system.

A biocompatible insulin delivery device is provided comprising an insulin reservoir sealed with a glucose-responsive plug or membrane. The plug functions to release insulin from the reservoir in response to a hyperglycemic glucose concentration and to prevent insulin release from the reservoir in response to hypoglycemic glucose concentration. In one embodiment, the plug is made of a biocompatible polymeric matrix comprising an inorganic component, a stimulus-responsive component and a catalytic component.

Disclosed is a method for obtaining glucose-regulated expression of active insulin in the cells of a mammalian subject. The method involves delivering into the subject a genetic construct comprising a coding sequence for a human proinsulin operably connected a promoter functional in the host cells. The construct includes a glucose responsive regulatory module having at least one glucose inducible regulatory element comprising a pair of CACGTG motifs linked by a five base nucleotide sequence, which confers glucose inducible expression of the proinsulin coding sequence. To ensure proper processing of the proinsulin to active insulin, the coding sequence was modified to direct the synthesis of a mutant proinsulin polypeptide having amino acid sequences that can be cleaved to mature insulin in suitable host cells, such as hepatocytes.

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.

Aspects of the disclosure generally relate to insulin delivery systems and compositions having a insulin secreting β cell line or insulin secreting recombinant non-β cells sequestered in a glucose-responsive material. The disclosed insulin delivery systems can be surgically implanted in a host and can provide a continuous source of insulin from the cells contained in the device. The combination of living cells with a glucose-responsive material provides a hybrid insulin delivery system that delivers physiologically relevant amounts of insulin in response to physiologically relevant glucose levels. In some aspects, the disclosed devices have a biphasic release of insulin in response to sudden increases in glucose concentrations in the fluids bathing the device.

The invention discloses a 3D printing microneedle patch for intelligent blood glucose regulation and a preparation method thereof, belonging to the biomedical field. The 3D printing microneedle patchof the invention is mainly made of photosensitive material with good biocompatibility, and comprises two parts of a substrate and a microneedle array, wherein the microneedle array comprises a plurality of conical microneedles, and the microneedles contain medicaments for intelligently regulating blood sugar, and the medicaments include carrier materials, glucose-responsive sensitive switching factors and medicaments molecules. The 3D printing microneedle patch of the invention is mainly made of photosensitive material with good biocompatibility. Firstly, the three-dimensional model of micro-needle patch is built by using modeling software, and the model is imported into the printing software of 3D printer. Then the 3D printing technology of photocuring is used to solidify the photosensitive material solution containing photoinitiator and drug according to the structure of the three-dimensional model of the micro-needle patch to obtain the 3D printing micro-needle patch. The microneedle patch of the invention can puncture the skin and intelligently release the loaded insulin according to the blood glucose concentration in the body so as to intelligently regulate the blood glucose level. The invention realizes painless, intelligent and responsive blood glucose regulation.

The invention discloses a glucose responsive gold nanoparticle and a preparation method and an application thereof. The method adopts the reversible addition-fragmentation chain transfer polymerization method to prepare isopropyl acrylamide-acrylyl sulfourea amino phenylboronic acid copolymer that which is modified to the surface of the gold nanoparticle to obtain the gold nanoparticle covered by the copolymer. The gold nanoparticle obtained through the method in disclosed by the invention can generate response with the glucose molecule in a solution; the developing system dispersed by the gold nanoparticle is driven through by the glucose molecule to change the colour of the gold nanoparticle solution at high temperature, so as to realize visual identification and detection for the glucose. The method in disclosed by the invention can be widely used for the field of nanometre bioanalysis.

A closed-loop insulin delivery system is described. More particularly, the presently disclosed insulin delivery system can comprise glucose-responsive vesicles that release insulin in response to hypoxia triggered by enzymatic reduction of glucose. In addition or as an alternative to insulin, the delivery system can release other diabetes treatment agents, such as non-insulin-based diabetes treatment agents. The vesicles can be prepared from a hypoxia sensitive polymer, such as a hypoxia-sensitive hyaluronic acid (HS-HA). The HS-HA can comprise hydrophobic groups that can be reduced in hypoxicenvironments to form hydrophilic groups. The vesicles can be loaded into microneedles and microneedle array patches for use in the treatment of diabetes or to otherwise regulate blood glucose levelsin subjects in need of such treatment.

The invention relates to hydrogel and organogel sensors as well as their application to continuous analyte monitoring. The sensor can include a hydrogel or organogel matrix. Standard and inverse designed are provided. In one embodiment, the matrix can include a molecular recognition agent for an analyte (e.g., a glucose analyte), and a volume resetting agent that reversibly binds with the molecular recognition agent. Reversible crosslinks between the molecular recognition agent and volume resetting agent can change the volume of the matrix upon interacting with the analyte via a competitive binding process. In various embodiments, the invention provides a hydrogel-based glucose sensor and sensors for continuous glucose monitoring. The glucose sensor can be based on a glucose-responsive hydrogel with a volume linearly correlated with glucose concentrations, such as about 0.05-50 mM, under physiological conditions. The invention thus provides a blood glucose monitor suitable for use in clinical settings.

The invention provides an isolated tissue specific glucose responsive promoter having a polymerase binding domain 3′ to at least one tripartite transcription factor binding cis element having a hepatocyte nuclear factor-1 (HNF-1) element, a CAAT / enhancer binding protein (C / EBP) response element and a glucose-response element (GRE). The promoter can include a second or third tripartite transcription factor binding cis element. A host cell including the tissue specific glucose responsive promoter of the invention also are provided. Further provided is a method of treating or preventing diabetes. The method includes administering to an individual an effective amount of a viral particle having a vector comprising a tissue specific glucose responsive promoter comprising a polymerase binding domain 3′ to at least one tripartite transcription factor binding cis element having a hepatocyte nuclear factor-1 (HNF-1) element, a CAAT / enhancer binding protein (C / EBP) response element and a glucose-response element (GRE) operationally linked to an insulin encoding nucleic acid, wherein expression of the insulin encoding nucleic acid is tissue specific and glucose responsive.

The present invention relates generally to a population of cells genetically modified to produce insulin in a glucose responsive manner and uses thereof. More particularly, the present invention relates to a population of cells genetically modified to produce insulin in response to physiologically relevant levels of glucose and uses thereof. The cells of the present invention are useful in a wide variety of applications, in particular in the context of therapeutic and prophylactic regimes directed to the treatment of diabetes and / or the amelioration of symptoms associated with diabetes, based on the transplantation of the cells of the present invention into mammals requiring treatment. Also facilitated is the design of in vitro based screening systems for testing the therapeutic effectiveness and / or toxicity of potential adjunctive treatment regimes.

The present invention relates generally to a population of cells genetically modified to comprise pancreatic islet glucokinase and capable of producing insulin in a glucose responsive manner and uses thereof. More particularly, the present invention relates to a population of cells so genetically modified capable of producing insulin in response to physiologically relevant levels of glucose and uses thereof. The cells of the present invention are useful in a wide variety of applications, in particular in the context of therapeutic and prophylactic regimes directed to the treatment of diabetes and / or the amelioration of symptoms associated with diabetes, based on the transplantation of the cells of the present invention into mammals requiring treatment. Also facilitated is the design of in vitro based screening systems for testing the therapeutic effectiveness and / or toxicity of potential adjunctive treatment regimes.

The invention provides a biodegradable and sugar responsive Y type polymer drug delivery material and preparation, which belongs to the field of biological materials. The structural formula of the compound is obtained by the following steps of firstly preparing a compound III, and then, preparing a compound V, and reacting the compound III with the compound V under conditions of cuprous bromide, copper bromide and divinyl pentamethylene triamine. The material provided by the invention has glucose responsive self-discipline insulin release ability and has selectivity on glucose concentration.

The invention relates to a gel material for efficient treatment of tumors and a preparation method thereof. The gel material is composed of a micro organic-inorganic hybrid nano-gel carrier and a bio-enzyme component loaded on the micro organic-inorganic hybrid nano-gel carrier. The micro organic-inorganic hybrid nano-gel carrier comprises an inorganic nanoparticle core and an organic gel layer compounded on the surface of the inorganic nanoparticle core, wherein the organic gel layer is formed by deposition and self-assembly of a gelling factor on the surface of the inorganic nanoparticle core, and the gelling factor is Fmoc- or Nap- functionalized small molecular polypeptide with an aromatic substituent group. Compared with the prior art, the micro organic-inorganic hybrid nano-gel carrier adopted by the invention provides natural protection for loading and immobilization of bio-enzyme, glucose responsive and reactive oxygen species responsive efficient and tandem enzyme-catalyzed reaction is carried out at a tumor site, tumor lesion site or other lesion sites to generate singlet oxygen, thus realizing efficient and safe treatment.

A biocompatible insulin delivery device is provided comprising an insulin reservoir sealed with a glucose-responsive plug or membrane. The plug functions to release insulin from the reservoir in response to a hyperglycemic glucose concentration and to prevent insulin release from the reservoir in response to hypoglycemic glucose concentration. In one embodiment, the plug is made of a biocompatible polymeric matrix comprising an inorganic component, a stimulus-responsive component and a catalytic component.

A method of improving the glucose response in glucose tolerant and intolerant subjects is provided. The method comprises providing to the subject probiotic compositions, or agents which specifically reduce bacterial species.

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 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.

The invention provides a preparation method of a controlled release carrier of a glucose-responsive drug, solves insufficiencies that ConA and sugar ligands thereof are needed to be modified in prior art. The method comprises: (1) dissolving sugar-containing polymer units in a lye, adding divinyl sulfone, adjusting a pH to stop reaction, and dialyzing to obtain a sugar-containing polymer with vinyl sulfone groups; (2) dissolving the prepared substances in a buffer solution, adding a ConA activating solution; (3) adjusting pH of the mixture obtained in step (2) by using the buffer solution, adjusting the pH, adding drop by drop the product into a mixed solution of cyclohexane and an emulsion stabilizer, reacting, removing an oil phase at an upper level, and depositing a lower level to obtain the glucose-responsive carrier. By introducing the divinyl sulfone into the ConA-sugar-containing polymer carrier, the preparation steps for the carrier can be simplified, the sugar-containing polymer can be directly crosslinked with the ConA, thereby being simple and high-efficiency to fix the ConA, low in cost, convenient to implement, and beneficial for large-scale production.

The device enables measurement of both of blood glucose level and hemoglobin A1c level, being small-sized and thus portable, allowing the measurement of a small amount of a specimen and, being usable in POC. The device comprises: a test-piece-mounting section (1) for detachably mounting test pieces (200) on which the blood specimen is to be spotted; a light-emitting section (2) for emitting light for irradiating the test pieces; a light-receiving section (3) for receiving reflected lights from the test pieces; and an operating section (4) for calculating the blood glucose level and hemoglobin A1c level of the blood specimen on the basis of photometric values obtained from the light-receiving section. For measuring the blood glucose level of the blood specimen, test piece (A) carries a composition reacting with glucose and showing color change. Test piece (B) carries a composition reacting with glycated hemoglobin and showing color change.

Methods, kits, compositions, and systems are provided for culturing pluripotent stem cells to produce populations of cells comprising beta-like cells (e.g., pancreatic lineage, glucose-responsive, and / or insulin-producing). In particular, culture conditions are provided that result in the generation of beta-like cells from a starting culture of human pluripotent stem cells.

The present invention includes compositions and methods for regenerating glucose-responsive cells by ultrasound-targeted microbubble destruction in the pancreas, wherein the composition comprises a pre-assembled liposome-nucleic acid complex in contact with in and about a microbubble, wherein the pre-assembled liposome-nucleic acid complex comprises a NeuroD gene under the control of the promoter, wherein disruption of the microbubble in the pancreas at a target site delivers the nucleic acid into pancreas cells at the location of the ultrasound disruption, wherein cells that incorporate the nucleic acid express insulin in response to high blood glucose levels.

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.

A biocompatible insulin delivery device is provided comprising an insulin reservoir sealed with a glucose-responsive plug or membrane. The plug functions to release insulin from the reservoir in response to a hyperglycemic glucose concentration and to prevent insulin release from the reservoir in response to hypoglycemic glucose concentration. In one embodiment, the plug is made of a biocompatible polymeric matrix comprising an inorganic component, a stimulus-responsive component and a catalytic component.

The present invention relates to glucose-responsive hyaluronic acid nanoparticles having boronic acid compounds chemically bonded thereto, and a composition including the same. When the nanoparticles according to the present invention are used, cancer may be diagnosed and treated using a cancer cell-specific biological mechanism, without the use of existing contrast agents and anticancer agents which have the problem of toxicity.

The invention discloses a finger blood test strip and a use method and a preparation method thereof. The finger blood test strip comprises a substrate and at least two blood sample test components, wherein each blood sample test component comprises an enzyme catalytic reaction coating, a working electrode, a reference electrode and an electric loop connection part which is matched and connected with the working electrode and the reference electrode; the enzyme catalyzing reaction coatings are connected with corresponding working electrodes and reference electrodes; at least one of the blood sample test components is a blood glucose test component; an enzyme on the enzyme catalytic reaction coating of the blood glucose test component is a bio-enzyme for catalyzing a reaction of blood glucose; at least one of the blood sample test components is a blood cholesterol test component; an enzyme on the enzyme catalytic reaction coating of the blood cholesterol test component is a bio-enzyme for catalyzing a reaction of blood cholesterol. By adopting the finger blood test strip, blood glucose detection and blood cholesterol detection are integrated on one test strip, so that pain caused by sampling blood repeatedly for a plurality of sample indexes is relieved for a user, the cost is lowered, benefit is increased, and large-scale volume production is facilitated.

The invention relates to an orderly porous polymer thin film, a preparation method and application in capture and controllable glucose-responsive release of insulin and belongs to the technical field of controllable release of drugs. The preparation method comprises the following steps of preparing an orderly cellular porous thin film of which the inner wall is loaded with a positively charged surfactant, selectively assembling a glucose-responsive material on the inner walls of pores of the orderly porous thin film, carrying out positioning capture on an insulin aggregate in the pores, carrying out controllable release on the insulin aggregate under the stimulated action of glucose and the like. According to the invention, the device is simple and convenient, the condition is mild, the insulin loading capacity is large, the release efficiency is high, the positioning capture of the insulin aggregate in the pores of the orderly cellular porous thin film can be achieved, and the insulin is efficiently released by virtue of the stimulation of glucose; furthermore, by virtue of changing the concentration of glucose, the regulation on the controllable release behavior of insulin is achieved and a glucose-responsive self-regulating insulin delivery system is established.

Insulin conjugates comprising an insulin analog 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.