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A kind of glucose-sensitive porous microsphere/polymer composite gel and its preparation method and application

A glucose-sensitive, porous microsphere technology, applied in the field of porous microsphere/polymer composite gel and its preparation, can solve complex problems, achieve large specific surface area, realize controllable release, and solve the effect of high-efficiency loading

Inactive Publication Date: 2019-06-04
TIANJIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] Aiming at the key problems faced by phenylboronic acid functionalized polymer hydrogel as insulin controlled release carrier, based on the idea of ​​system engineering, the present invention develops and designs a glucose-sensitive porous microsphere / polymer composite gel under the physiological condition of pH 7.4. Gel system, the composite gel system synergistically integrates the implantable positioning performance of the gel carrier, the stimuli-responsive function and the high-efficiency loading characteristics of the porous microspheres, which is expected to solve the complexities faced by the insulin physiological self-regulating implantable gel delivery system. question

Method used

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  • A kind of glucose-sensitive porous microsphere/polymer composite gel and its preparation method and application
  • A kind of glucose-sensitive porous microsphere/polymer composite gel and its preparation method and application
  • A kind of glucose-sensitive porous microsphere/polymer composite gel and its preparation method and application

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Embodiment 1: Preparation of PLGA porous microspheres of different shapes

[0054] (1) Preparation of PLGA porous microspheres with BSA as porogen

[0055] Weigh 500 mg of PLGA polymer with a ratio of lactic acid to glycolic acid of 50:50 and a molecular weight of 5000 g / mol, and dissolve it in 3 mL of dichloromethane. Then weigh 400 mg porogen BSA and dissolve it in 0.6 mL water, emulsify PLGA dichloromethane solution and BSA aqueous solution 12 times with a cell disruptor to form W1 (inner water phase) / O (oil phase) emulsion. After allowing the emulsion to be dispersed in 300mL 0.4% PVA aqueous solution, high-speed shearing (7000r / min) forms a W1 / O / W2 double-emulsion system, and the organic solvent is evaporated at room temperature, and centrifugally dried to obtain PLGA porous microspheres. The average particle size of the microspheres is about 20 μm.

[0056] (2) Preparation of PLGA porous microspheres with ammonium bicarbonate as porogen

[0057] Weigh 500 mg of...

Embodiment 2

[0062] Embodiment 2: Preparation of phenylboronic acid surface-modified PLGA porous microspheres

[0063] (1) Preparation of phenylboronic acid surface-modified PLGA porous microspheres by indirect modification method

[0064] The process of preparing phenylboronic acid surface-modified PLGA porous microspheres by indirect modification method is shown in the attached image 3As shown, the carboxyl groups on the surface of PLGA porous microspheres were first aminated with ethylenediamine, and then polyacrylic acid was grafted on the surface of the PLGA microspheres, and then the carboxyl groups on the polyacrylic acid chain segment reacted with the amino group of aminophenylboronic acid. The phenylboronic acid is bonded to the surface of the PLGA microsphere to prepare the PLGA porous microsphere with the surface modified by the phenylboronic acid. Aminophenylboronic acid includes p-aminophenylboronic acid, m-aminophenylboronic acid and o-aminophenylboronic acid, among which t...

Embodiment 3

[0068] Example 3: Loading of phenylboronic acid surface-modified PLGA porous microspheres on insulin

[0069] Disperse the insulin in an appropriate amount of water, adjust the pH value of the solution to 1.0-7.4 by dropping dilute hydrochloric acid, adjust the solubility of insulin in water, and centrifuge to take the supernatant to obtain insulin-saturated aqueous solutions with different concentrations. Then take 2 mL of a saturated aqueous solution of insulin, add 100 mg of phenylboronic acid surface-modified PLGA porous microspheres, stir gently for 2-24 hours, centrifuge, and freeze-dry to obtain insulin-loaded phenylboric acid surface-modified PLGA porous microspheres. By testing the concentration change of the insulin solution before and after being loaded by the microspheres, the loading capacity of the PLGA porous microspheres on insulin can be calculated. The loading capacity of PLGA porous microspheres to insulin is about 10-45%.

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Abstract

The invention relates to glucose sensitive porous microsphere / polymer composite gel as well as a preparation method and application thereof. In the glucose sensitive porous microsphere / polymer composite gel, porous microspheres are polylactic acid-glycolic acid copolymer (PLGA) porous microspheres, and the average particle size of the PLGA porous microspheres is 1-20mu m; and the polymer is hyaluronic acid containing a catechol group. The preparation method of the porous microsphere / polyhydroxylated polymer composite gel comprises the following steps: blending the porous microspheres subjected to surface modification by phenylboronic acid with the aqueous solution of the polyhydroxylated polymer; and carrying out bonding reaction between phenylboronic acid on the surfaces of the microspheres and cis-dihydroxy on the chain segment of the polyhydroxylated polymer to form a cross-linked polymer network, thereby obtaining the composite gel. The glucose sensitive porous microsphere / polymer composite gel is applied to a drug delivery system, is used for developing insulin implanted gel long-acting sustained release preparations, and has great application values in the field of development of a new dosage form for treating diabetes.

Description

technical field [0001] The invention relates to a porous microsphere / polymer composite gel and a preparation method thereof. The composite gel system has glucose sensitivity, can efficiently load a large amount of insulin, and can regulate insulin activity in response to changes in glucose concentration under the physiological condition of pH 7.4. The invention belongs to the field of medicinal polymer hydrogel. Background technique [0002] Diabetes and its complications have become a major public health crisis in my country. Diabetes is a metabolic disease caused by relative or absolute deficiency of insulin secretion, so since insulin was discovered and successfully extracted, it has been the drug of choice for diabetes treatment. At present, the main route of clinical insulin administration is subcutaneous injection. Diabetic patients often need frequent injections for a long time, which is not only costly, inconvenient to administer, but also has many adverse reaction...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/06A61K47/36A61K47/18A61K9/50A61K47/34A61K47/10A61K38/28A61P3/10
CPCA61K9/0002A61K9/06A61K9/5015A61K9/5031A61K38/28A61K47/18A61K47/36
Inventor 张建华姚丹郭睿威董岸杰
Owner TIANJIN UNIV
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