32 results about "Glucose sensitivity" patented technology

The invention relates to methods for generating insulin secreting cells from precursor stem cells or from adult pancreatic exocrine cells. The methods of the invention are useful, for example, for generation of glucose sensitive insulin-secreting beta-cells suitable for transplantation, as well as for in situ development of insulin-secreting cells in a patient in need thereof. Further, the method of the invention relates to methods for preventing premature differentiation of precursor stem cells into insulin-secreting beta-cells. Still further, the invention relates to assay methods for identification of compounds that prevent or activate beta-cell differentiation.

The invention discloses a preparation method of quick-response glucose-sensitive hydrogel which is quick in response to glucose stimulation in a physiological environment. The preparation method particularly includes adding acrylamidophenylboronic acid and acrylic acid amino ester, N-alkyl acrylamide and acrylamide or methacrylamide and N,N'-methylenebisacrylamide into an alkaline macromolecule aqueous solution, and stirring to dissolve completely so as to obtain a mixed solution; adding catalytic reaction accelerators tetramethylethylenediamine into the mixed solution with uniformly mixing; adding initiators accounting for 0.03-0.3% of monomer mass, into the obtained solution, and conducting room temperature reaction to obtain the hydrogel containing a macromolecular copolymer shown as structural formula (I). Alkaline macromolecules in the preparation method are a macromolecule component containing amino or partially containing lactam group and can enhance glucose sensitivity and responsiveness of the hydrogel in the physiological environment by being added, so that stability in use of the hydrogel is improved.

The invention relates to a preparation method of a pH and glucose dual-sensitive mesoporous silica@polymer drug carrier, and belongs to the technical field of nanomaterials. The preparation method comprises the following steps: 1, preparing catechol modified mesoporous silica; 2, preparing a phenylboric acid-containing polymer; and 3, dispersing catechol modified mesoporous silica in methanol to prepare a third solution, dissolving the phenylboric acid-containing polymer in methanol to prepare a fourth solution, adding the fourth solution to the third solution, reacting for 12-24h, and centrifuging after the reaction to remove unreacted polymer in order to obtain the carrier. Aminated mesoporous silica is modified with 3,4-dihydroxy benzaldehyde to make the surface of the mesoporous silica have a dihydroxy phenol structure and connected with a pH-sensitive imine bond; and the synthesized phenylboric acid-containing polymer and the dihydroxy phenol structure on the surface of the mesoporous silica form a glucose-sensitive borate ester bond, and the polymer is modified with polyethylene glycol, so the biocompatibility is good.

The invention discloses a new method for preparing an intelligent glucose-sensitive insulin controlled-release biological material. The method comprises the following steps of: firstly, dissolving glucose derivative monomers with C=C derivatives and concanavalin A derivative monomers with C=C double bonds in buffer solution to produce monomer solution; secondly, adding a catalyst in the monomer solution to perform free radical polymerization at a certain temperature; and finally, removing unreacted reactant through dialysis to obtain the glucose-sensitive insulin controlled-release biologicalmaterial. The preparation method has the advantages of convenient implementation, fast reaction process, mild reaction condition and easy production preparation on a large scale. The obtained glucan-concanavalin A insulin controlled-release biological carrier material has the advantages of good glucose-sensitive property and excellent insulin controlled-release performance.

The invention relates to the field of macromolecules, in particular to a thiol/boronic group modified polymer, a glucose-sensitive hydrogel composition, glucose-sensitive drug-loaded hydrogel and a preparation method thereof. The thiol/phenylboronic group modified polymer is dispersed in a polysaccharide aqueous solution with an o-diol structure, and is stirred to swell under a near-neutral condition, so that the glucose sensitive hydrogel is obtained by utilizing spontaneous oxidation of the thiol group and condensation crosslinking of the boronic acid groups and the o-diol in the molecules. The preparation method of the glucose-sensitive hydrogel is simple, a condensing agent or a free radical initiator does not need to be added, and the glucose-sensitive hydrogel has good injectability, biocompatibility and glucose sensitivity. When the hydrogel is used as a drug carrier, only the drug needs to be added into the glucose sensitive hydrogel to be dissolved or uniformly dispersed. According to the prepared glucose-sensitive drug-loaded hydrogel, the release speed and release behavior of the drug can be adjusted by responding to the change of the glucose concentration, so that the drug can be quickly released when the glucose concentration is high.

The invention provides a polymer shown in the formula (I). The invention also provides glucose-sensitive nanogel. The glucose-sensitive nanogel comprises polymer nanogel and glucose oxidase electrostatically compounded with the polymer nanogel. The polymer nanogel is obtained by crosslinking of the polymer shown in the formula (1) and sodium perselenide. The preparation method of the glucose-sensitive nanogel comprises the following steps that the polymer shown in the formula (1) and a sodium perselenide aqueous solution undergo a crosslinking reaction in an organic solvent to produce the polymer nanogel; and the polymer nanogel and glucose oxidase undergo an electrostatic compounding reaction in an aqueous solution to produce the glucose-sensitive nanogel. The glucose-sensitive nanogel has good oxidation sensitivity, biocompatibility and glucose sensitivity, can adjust drug release rate and release behavior by responsing a glucose concentration change when being used as a drug carrier, and can realize fast drug release at a high glucose concentration.

The invention discloses new long-acting GLP-1 (glucagonlike peptide-1) compounds, a medicine composition containing the compounds, wherein the compound is used for (1) treatments of hyperglycemia, type 2 diabetes, type 1 diabetes, impaired glucose tolerance, obesity, hypertension, X syndrome, dyslipidemia, cognitive disorder, myocardial infarction, coronary heart disease and other vascular diseases, apoplexy, dyspepsia and gastric ulcer, (2) or reducing food intake and beta-cell apoptosis, enhancing beta-cell function and beta-cell quantity , and or, recovering the glucose sensitivity of beta-cell.

The invention provides a phenylboronic acid functionalized zwitterion blocked copolymer and a glucose-sensitive bionic nano-carrier. The phenylboronic acid functionalized zwitterion blocked copolymer is of a structure shown as a formula I. The phenylboronic acid functionalized zwitterion blocked copolymer and the glucose-sensitive bionic nano-carrier have the advantages that the phenylboronic acid functionalized zwitterion blocked copolymer and polyglutamic acid ester are excellent in biocompatibility, and the polyglutamic acid ester is excellent in biodegradability and is modified by phenylboronic acid; the glucose-sensitive bionic nano-carrier is excellent in biocompatibility and biodegradability; the glucose-sensitive bionic nano-carrier is excellent in glucose-sensitive property owing to special boron ester bond forming reaction between the phenylboronic acid and 1, 2-diol, can quickly react to change of the concentration of glucose and is favorable for releasing glucose-sensitive medicines, and accordingly curative effects of the medicines can be improved; the phenylboronic acid functionalized zwitterion blocked copolymer can be effectively applied to the field of biological application, is excellent in glucose-sensitive medicine release performance and has potential diabetes mellitus treatment application.

The invention relates to self-assembled nanoparticles having glucose sensitivity and temperature sensitivity and a preparation method of nanoparticles. The nanoparticles consist of the following components: 3-acrylamidophenylboronic acid AAPBA and N-vinylcaprolactam NVCL. The preparation method comprises the following steps: mixing the AAPBA, the NVCL and an initiating agent, and dissolving an obtained mixture in a solvent; in an anaerobic condition, conducting a reversible addition reaction, so that a polymer p (NVCL-co-AAPBA); and dissolving the polymer in ultra-pure water, and conducting rotating at 300r/min for 3h, so that the self-assembled nanoparticles having glucose sensitivity and temperature sensitivity are obtained. The method disclosed by the invention is simple and rapid in reaction; the nanoparticles can be used for encapsulating insulin, and the drug-release rate of the encapsulated insulin can be changed along with the increase in glucose concentration; therefore, the nanoparticles have a good practical value.

The invention discloses a glucose and H2O2 dual-response double-layer cross-linked polymer nano drug delivery system as well as a preparation method and application thereof. Polyethylene glycol, functionalized carbonic ester and sulfydryl-containing carboxylic acid are sequentially subjected to ring-opening polymerization reaction to form an amphiphilic triblock polymer skeleton, and the amphiphilic triblock polymer skeleton is modified by a phenylboronic acid derivative to form an amphiphilic polymer; gOx is sequentially modified by carboxylic acid containing double bonds and vicinal diol substances, and then the modified GOx is mixed with the amphiphilic polymer. The novel biodegradable polymer auxiliary material is designed and synthesized by organically combining GOx serving as a glucose oxidation mechanism, a competitive mechanism between sugar molecules and acyclic diol and gel ultraviolet crosslinking for the first time. GOx and phenylboronic acid ester act together to enhance glucose sensitivity and H2O2 sensitivity; the phenylboronic acid derivative and the vicinal diol compound form phenylboronic acid ester, and the phenylboronic acid ester and the polymer nanoparticles are subjected to ultraviolet crosslinking to form a double-layer cross-linked structure, so that the stability is improved, and long-acting circulation of insulin in vivo is realized.

This invention relates to glucose-sensitive albumin-binding diboron conjugates. More particularly the invention provides novel diboron compounds, and in particular diboronate or diboroxole compounds, useful as intermediate compounds for the synthesis of diboron conjugates. The diboron compounds are characterized by formula (I), which is: R1-X—R2, and wherein “X” is a mono- to multiatomic linker and where R¹ and R², which may be identical or different, each represents a group of Formula (11a) or (IIb) Also described are diboron conjugates represented by the general Formula (I′), which is: R1′-X′—R2′, in which either the moeities R1′ or R2′ or X′ carry a drug that is covalently attached to the diboron compound.

The present invention provides methods for determining a putative agent that treats or prevents obesity and/or diabetes or increasing insulin sensitivity, the method comprising contacting cells with the putative agent and measuring thioredoxin-interacting protein (TXNIP) or thioredoxin expression or activity in the cells. The present invention also provides the agent, the pharmaceutical composition, and methods of preventing or treating obesity and/or diabetes or of increasing insulin sensitivity or glucose sensitivity, the method comprising administration of the agent that decreases the expression of TXNIP or activity of TXNIP.

The invention relates to application of ZNRF3/RNF43 in preparation of a medicine for regulating energy metabolism. It proves that the ZNRF3/RNF43 double knockout can reduce the blood sugar content andserum insulin level, increase the sensitivity of the body to glucose and down-regulate the expression of glucose allogeneic related genes; meanwhile, liver lipid deposition is reduced, lipid synthesis and expression of inflammation-related genes are reduced, it is shown that the ZNRF3/RNF43 double knockout can improve liver insulin resistance possibly through the ways of influencing glycoxenesis,lipid synthesis and the like, and then a theoretical basis is provided for preparing energy metabolism regulating medicine.

The present invention relates to a conjugate of the formula P-L-I, wherein P is a peptide hormone effecting the metabolism of carbohydrates in vivo, L is a hydrolysable linker molecule consisting of L_p and L_i, and I is a molecule capable of inhibiting the effect of the peptide hormone P on the metabolism of carbohydrates in vivo. Under in vivo conditions, the conjugate is the major compound. When the concentration of glucose increases in vivo, the concentration of the peptide hormone effecting the metabolism of carbohydrates in vivo also increases.

Disclosed herein are glucose-sensitive drug delivery systems including polymeric shell encapsulating an active agent. Upon exposure to a sufficient concentration of glucose, the shell is ruptured, releasing the active agent for absorption.

The present invention provides glucose sensitive insulin derivatives comprising a macrocycle, a glucose mimetic and human insulin or an analogue thereof, and their pharmaceutical use. Furthermore, the invention relates to pharmaceutical compositions comprising such glucose sensitive insulin derivatives, and to the use of such compounds for the treatment or prevention of medical conditions relating to diabetes.