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In-vivo in-situ drug-loading hydrogel carrier as well as preparation method and applications thereof

A hydrogel and carrier technology, applied in prosthesis, medical science, tissue regeneration, etc., can solve the problems of poor fusion rate, no bionic artificial bone marrow stent, etc., and achieve the effect of improving spinal fusion

Inactive Publication Date: 2017-06-20
SECOND AFFILIATED HOSPITAL SECOND MILITARY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Literature (Xu Guohua, 3D Artificial Bones for Bone Repair Prepared by Computed Tomography-Guided Fused Deposition Modeling for Bone Repair.ACSAppl.Mater.Interfaces, 2014; Sol–gel derived mesoporous 58S bioactive glasscoatings on AZ31magnesium alloy and in vitro CoatingSurfaceSlogatnohavior, , 2014; Chinese patent CN102532585B, preparation method of chondroitin sulfate cross-linked collagen / hydroxyapatite composite scaffold material) published about the improvement of tissue engineering bone, such as clinically used bone cement, intervertebral fusion device, etc. To mechanical support, may lead to defects such as poor fusion rate
[0004] At present, there are no related literature reports on in situ drug-loaded hydrogel carriers that can be used for bionic artificial bone marrow scaffolds

Method used

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  • In-vivo in-situ drug-loading hydrogel carrier as well as preparation method and applications thereof
  • In-vivo in-situ drug-loading hydrogel carrier as well as preparation method and applications thereof
  • In-vivo in-situ drug-loading hydrogel carrier as well as preparation method and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1 Preparation of in situ drug-loaded hydrogel carrier PLGA-PEG-PLGA in vivo

[0036] The following raw materials: polyethylene glycol PEG (1500) (Aldrich-Sigma Co.), lactide DL-lactide (LA) (Purac), glycolide (GA) (Purac), stannous octoate (99%, Aldrich-SigmaCo.), and anhydrous toluene and dichloromethane are all commercially available.

[0037] Add 20g of PEG (1500) with double-terminated hydroxyl groups in a 250ml flask, heat the oil bath to 120°C, remove water under reduced pressure for 4 hours, then add 48.8g of monomer lactide (LA) and 12.2g of glycolide ( GA) with a molar ratio of 4:1, heat in a vacuum environment until it is completely melted, add 150 microliters of stannous octoate anhydrous toluene solution to catalyze, remove toluene under reduced pressure for 1 hour, heat the oil bath to 150°C and continue the reaction under argon 6 hours.

[0038] After the reaction was completed, the temperature was lowered to 100°C, and unreacted monomers and low...

Embodiment 2

[0039] Embodiment 2 Hydrogel Carrier Number Average Molecular Weight, Molecular Weight Distribution, Determination of Transformation Temperature

[0040] 1. The actual number-average molecular weight obtained by calculating the PLGA-PEG-PLGA hydrogel carrier prepared in Example 1 according to NMR is 1744-1500-1744, LA:GA=4:1, such as figure 1 shown.

[0041] 2. The PLGA-PEG-PLGA of embodiment 1 is analyzed and calculated by GPC as a homogeneous substance, its number average molecular weight Mn: 5956, weight average molecular weight Mw: 8732, molecular weight distribution coefficient D: 1.26, as figure 2 shown.

[0042] 3. Configure a 25wt% solution of PLGA-PEG-PLGA with physiological saline, and its rheological diagram is as follows image 3 As shown, it can be seen that when the heating rate reaches about 27-30°C at a rate of 0.5°C / min, the hydrogel begins to change phases, and when it exceeds 30°C, it basically changes from a flowing sol state to a solid gel state (such a...

Embodiment 3

[0043] Example 3 Preparation of rhBMP2 / rhVEGF165-loaded gel PLGA-PEG-PLGA

[0044] The drug-loaded hydrogel carrier PLGA-PEG-PLGA prepared in Example 1 was dissolved in physiological saline to prepare 40ml of a 25wt% hydrogel solution, which was sterilized by 7kGy irradiation (the second military medical university irradiated Center) and put it in a refrigerator at 4°C for 24 hours until it becomes a homogeneous solution state. At room temperature (below 25°C), use a 5ml sterile syringe to extract 14ml of hydrogel solution containing 500ug of rhVEGF165 in a sterile ultra-clean bench In the reagent bottle, the reagent bottle mixed with hydrogel and rhVEGF was placed in a mixer and mixed for 5 minutes to prepare a mixture V solution containing 36ug / ml of VEGF;

[0045] Inject 14ml of the hydrogel solution into a reagent bottle containing 5mg of rhBMP-2 to prepare a mixture B solution containing rhBMP-2 at a concentration of 360ug / ml;

[0046] Take a sterile centrifuge tube (15m...

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Abstract

The invention relates to the technical field of medicinal preparations, and in particular relates to an in-vivo in-situ drug-loading hydrogel carrier as well as a preparation method and applications of the in-vivo in-situ drug-loading hydrogel carrier. For the in-vivo in-situ drug-loading hydrogel carrier PLGA-PEG-PLGA, the hydrogel carrier is formed by polymerizing lactide LA, polyethylene glycol PEG and glycolide GA, wherein the number average molecular weight ratio of PLGA to PEG is (1.5-3):1, and the molar ratio of LA to GA is (3-5):1. For the in-vivo in-situ drug-loading hydrogel carrier provided by the invention, by embedding bone growth promoting factors, when natural marrow fills a porous artificial bone scaffold, the release of important signal factors during the fracture repairing process can be simulated, and thus the in-vivo in-situ drug-loading hydrogel carrier is well applied to the fields of improving spinal fusion, bone ununion, bone defect repair, and the like.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical preparations, in particular to an in-situ drug-carrying hydrogel carrier in vivo and a preparation method and application thereof. Background technique [0002] The use of materials to embed drugs to delay drug release, improve drug efficacy and targeting has been widely used in clinical practice. Among them, BMP-2 has been widely used in clinical spinal intervertebral fusion, nonunion, repair of large bone defects, etc., showing its great potential to replace autologous bone repair. However, the current BMP-2 product "BMP-2+ACS" approved by PDA for clinical use has poor adhesion of BMP-2 in solution state, which leads to surrounding spread and complications such as heterotopic ossification. Enzymolysis improves the effect of BMP-2, BMP-2 supraphysiological dose (mg / ml) leads to side effects such as poor quality of bone formation, bone cysts, adipogenesis, etc. Slow release carrier. Ther...

Claims

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Application Information

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IPC IPC(8): A61L27/18A61L27/54C08G63/664C08L67/04
CPCA61L27/18A61L27/54A61L2300/252A61L2300/414A61L2430/02A61L2430/38C08G63/664C08L67/04
Inventor 许国华鲍小刚俞麟朱领军
Owner SECOND AFFILIATED HOSPITAL SECOND MILITARY MEDICAL UNIV
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