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Preparation method and application of cyclodextrin-drug host-guest supramolecular modified hydrogel

A cyclodextrin and hydrogel technology is applied in the field of repair of human cartilage and bone damaged tissue, which can solve the problems of poor long-term curative effect, poor tissue adaptability of microfracture surgery, and high recurrence rate, and achieve prolonged effect. Effect

Inactive Publication Date: 2019-05-24
SOUTH CHINA UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among the surgical transplantation methods used, mosaic transplantation and microfracture surgery have poor tissue adaptability, high recurrence rate, and poor long-term efficacy

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment example 1

[0018] 1. Preparation of photo-crosslinked hydrogel raw materials

[0019] (1) Dissolve 4g (400-1000KDa) of hyaluronic acid in DPBS solution and mix with 8.7ml of excess methacrylic anhydride, adjust the pH to 7.5-8.5, react at 4°C for 3 hours, and react at room temperature overnight, precipitation with ethanol, and water After 5 days of dialysis, the residue of small molecules was removed, and the double bond modified hyaluronic acid powder, namely HAMA, was lyophilized.

[0020] (2) After the β-cyclodextrin (1eq) and isocyanoethyl methacrylate (2eq) after being vacuum dried to completely remove the water, dissolved and mixed in DMF solvent, add a small amount of Sn(Oct) 2 (3μM) as a catalyst, react at room temperature for 4h under the protection of nitrogen atmosphere. Then the product was poured into 10 times volume of ice acetone to precipitate, and dried under vacuum to obtain β-cyclodextrin double bond modified product: β-CD-AOI.

[0021] 2. The subject and object combination ...

Embodiment example 2

[0026] 1. Preparation of photo-crosslinked hydrogel raw materials

[0027] (1) Synthesis of GelMA: first dissolve gelatin (type A, 15g) in 150mL DPBS solution (pH 7.4), react with methacrylic anhydride at 40℃ for 3h, then add excess 25℃ DPBS solution to dilute and terminate the reaction Progress, dialyze at 40°C for 5 days and freeze-dry for use.

[0028] (2) The difference from embodiment 1 is that this embodiment uses isocyanate ethyl acrylate to react with β-cyclodextrin, and the feed ratio is β-cyclodextrin:isocyanate ethyl acrylate=1:1.

[0029] 2. The host-guest combination of lipophilic drugs and β-cyclodextrin

[0030] The difference from Example 1 is that in this example, β-CD-AOI and melatonin are stirred in ultrapure water for 24 hours to form host-guest supramolecules. Freeze-dried for later use.

[0031] 3. Preparation of cell-carrying cyclodextrin-drug host-guest supramolecular modified hydrogel

[0032] The difference from Example 1 is that the host and guest supramolecu...

Embodiment example 3

[0034] Different from the implementation cases 1 and 2, this implementation case combines the previous two and disperses the host and guest supramolecules of β-CD-AOI and melatonin in a 10% GelMA solution and adds 0.5% I2959 initiator , Mixed with stem cell BMSCs and injected into the lower layer of the osteochondral defect, according to the 5.6mW ultraviolet light, room temperature crosslinking for 2min. Disperse the host and guest supramolecules of β-CD-AOI and Kartogenin in a 2% HAMA solution, add 0.5% I2959 initiator, add stem cell BMSCs, mix well, and inject into the upper layer of the GelMA preliminary cross-linked hydrogel. After 2 minutes Under 5.6mW ultraviolet light, crosslinking at room temperature for 5min. The β-cyclodextrin-drug host-guest supramolecular modified biphasic hydrogel is obtained. When used for osteochondral repair, the thickness of the bone and cartilage layer should be considered, and the corresponding photo-crosslinked hydrogel solution should be i...

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Abstract

The invention discloses a preparation method and application of cyclodextrin-drug host-guest supramolecular modified hydrogel, which comprises the following steps: firstly, adopting cyclodextrin derivatives grafted with double bonds to include lipophilic drugs under the action of host-guest to form nano drug boxes which are uniformly dispersed under the condition of water phase; then introducing the nano drug boxes into a photocrosslinkable hydrogel solution to crosslink under ultraviolet light to form a corresponding liquid drug-carrying gel matrix. According to the invention, the crosslinking density, mechanical strength and drug-carrying density of the hydrogel can be adjusted by changing the grafting rate and mass fraction of the ingredients. The hydrogel has good biocompatibility andcan be used for three-dimensional culture of cells, can encapsulate stem cells with rapid proliferation and multiple differentiation potentials and achieves directional differentiation of the stem cells under the induction of drugs. The material is combined with stem cell therapy to achieve rapid tissue repair, which has obvious advantages.

Description

Technical field [0001] The invention relates to the technical field of repairing human cartilage and bone damaged tissue parts, in particular to a preparation method and application of a cyclodextrin-drug host-guest supramolecular modified hydrogel. Background technique [0002] The most commonly used clinical methods to treat bone and cartilage injuries include physical therapy, drug therapy (including anti-inflammatory drugs, bone resorption inhibitors, metal enzyme inhibitors, etc.), surgical transplantation (including mosaic transplantation, microfracture, Autologous or allogeneic bone grafting), but these methods have some disadvantages. Physical therapy is very limited and can only relieve pain and delay the condition. Clinically, drug therapy has limited efficacy and has certain side effects on the normal metabolism of human cartilage, so it cannot be used for a long time. Among the surgical transplantation methods used, mosaic transplantation and microfracture surgery h...

Claims

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Application Information

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IPC IPC(8): C08J3/075C08B37/08C08B37/16C08H1/00A61L27/22A61L27/20A61L27/38A61L27/52A61L27/54C08L5/16C08L5/08C08L89/00
Inventor 施雪涛刘雪敏
Owner SOUTH CHINA UNIV OF TECH
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