MEDICAL HYDROGEL

Abstract

A medical hydrogel is formed by in-situ crosslinking an aldehyde-terminated multi-arm star polyethylene glycol and a polyamino compound. The aldehyde group and the multi-arm star polyethylene glycol are linked by a chemical bond such as an ether bond, an amide bond, a urethane bond, an imine bond, or a urea bond. The aldehyde group at the end of the multi-arm polyethylene glycol reacts with the amino group in the polyamino compound to produce Schiff base for crosslinking so that the medical injectable gel is formed. The prepared gel has a short gelling time, a desired gel burst strength, and a good stability in an aqueous solution.

Claims

1. A medical hydrogel, formed by in-situ crosslinking an aldehyde-terminated multi-arm star polyethylene glycol and a polyamino compound, wherein the aldehyde group and the multi-arm star polyethylene glycol are linked by a chemical bond such as an ether bond, an amide bond, a urethane bond, an imine bond, or a urea bond.

2. The medical hydrogel according to claim 1, wherein the polyamino compound is selected from one or more of polyethylenimine and polylysine.

3. The medical hydrogel according to claim 1, wherein the aldehyde-terminated multi-arm star polyethylene glycol is a multi-arm polyethylene glycol with not less than 2 arms and a molecular weight of not less than 2000.

4. The medical hydrogel according to claim 1, wherein the aldehyde-terminated multi-arm star polyethylene glycol has 2-8 arms.

5. The medical hydrogel according to claim 1, wherein the aldehyde group is selected from one or more of aromatic aldehydes and alkyl aldehydes.

6. Use of the medical hydrogel according to claim 1 in postoperative tissue closure and anti-leakage, anti-tissue adhesion, tissue filling, tissue repair, skin dressing, and pharmaceutical preparation.

7. A method for preparing the medical hydrogel according to claim 1, comprising: dissolving the aldehyde-terminated multi-arm star polyethylene glycol in a pH 4-10 buffer to prepare an aldehyde-terminated multi-arm star polyethylene glycol solution; dissolving the polyamino compound in a pH 4-10 buffer to prepare a polyamino compound solution; and mixing the two solutions to obtain the medical hydrogel.

8. The method for preparing the medical hydrogel according to claim 7, wherein the aldehyde-terminated multi-arm star polyethylene glycol solution has a final concentration of 2-30%, and the polyamino compound solution has a concentration of 0.5-20%.

9. The method for preparing the medical hydrogel according to claim 7, wherein the aldehyde-terminated multi-arm star polyethylene glycol solution has a final concentration of 10-20%, and the polyamino compound solution has a concentration of 1-5%.

10. The method for preparing the medical hydrogel according to claim 7, wherein the molar ratio of the aldehyde group in the aldehyde-terminated multi-arm star polyethylene glycol to the amino in the polyamino compound is 0.01-5:1.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0026] FIG. 1 shows the observation results of the gelling stability of an ether bond-linked, amide bond-linked, and ester bond-linked aldehyde-terminated polyethylene glycols.

DETAILED DESCRIPTION

[0027] The specific steps of the present invention are described by the following examples, but are not limited to the examples.

[0028] The terms used in the present invention, unless otherwise stated, generally have the meanings commonly understood by those of ordinary skill in the art.

[0029] The present invention is further described below in detail with reference to specific examples and relevant data. It should be understood that the examples are only used to exemplify the present invention, but do not limit the scope of the present invention in any manner.

[0030] In the following examples, various processes and methods that are not described in detail are conventional methods known in the art.

[0031] The present invention is further described below with reference to specific examples, but the protection scope of the present invention is not limited to this.

Example 1

[0032] 600 mg of an ether bond-linked benzaldehyde-terminated eight-arm polyethylene glycol (8-PEG-O-BA, M.W. 10K) was dissolved in 2 mL of phosphate buffer (pH 7.4) to afford solution A. A solution of 2.2% (w/v) of polyethylenimine in phosphate buffer was prepared as solution B. The solution A and the solution B were mixed in equal volume to obtain a viscous hydrogel with a gelling time of 21 seconds and a gel burst strength of 16 kPa.

Example 2

[0033] 600 mg of an ether bond-linked benzaldehyde-terminated eight-arm polyethylene glycol (8-PEG-O-BA, M.W. 13.5K) was dissolved in 2 mL of phosphate buffer (pH 7.4) to afford solution A. A solution of 1.67% (w/v) of polyethylenimine in phosphate buffer was prepared as solution B. The solution A and the solution B were mixed in equal volume to obtain a viscous hydrogel with a gelling time of 22 seconds and a gel burst strength of 11 kPa.

Example 3

[0034] 400 mg of an amide bond-linked benzaldehyde-terminated eight-arm polyethylene glycol (8-PEG-amide-BA, M.W. 10K) was dissolved in 2 mL of phosphate buffer (pH 7.4) to afford solution A. A solution of 1.48% (w/v) of polyethylenimine in phosphate buffer was prepared as solution B. The solution A and the solution B were mixed in equal volume to obtain a viscous hydrogel with a gelling time of 2 seconds and a gel burst strength of 13 kPa.

Example 4

[0035] 600 mg of an amide bond-linked benzaldehyde-terminated four-arm polyethylene glycol (4-PEG-amide-BA, M.W. 10K) was dissolved in 2 mL of phosphate buffer (pH 7.4) to afford solution A. A solution of 2.2% (w/v) of polyethylenimine in phosphate buffer was prepared as solution B. The solution A and the solution B were mixed in equal volume to obtain a viscous hydrogel with a gelling time of 20 seconds and a gel burst strength of 11 kPa.

Example 5

[0036] 400 mg of an amide bond-linked benzaldehyde-terminated eight-arm polyethylene glycol (8-PEG-amide-BA, M.W. 10K) was dissolved in 2 mL of phosphate buffer (pH 7.4) to afford solution A. A solution of 2.44% (w/v) of polylysine in phosphate buffer was prepared as solution B. The solution A and the solution B were mixed in equal volume to obtain a viscous hydrogel with a gelling time of 5 seconds and a gel burst strength of 21 kPa.

Example 6

[0037] 400 mg of an amide bond-linked benzaldehyde-terminated eight-arm polyethylene glycol (8-PEG-amide-BA, M.W. 10K) was dissolved in 2 mL of phosphate buffer (pH 7.4) to afford solution A. A solution of 3.66% (w/v) of polylysine in phosphate buffer was prepared as solution B. The solution A and the solution B were mixed in equal volume to obtain a viscous hydrogel with a gelling time of 5 seconds and a gel burst strength of 25 kPa.

Example 7

[0038] 600 mg of an ether bond-linked propionaldehyde-terminated eight-arm polyethylene glycol (8-PEG-O-PA, M.W. 10K) was dissolved in 2 mL of phosphate buffer (pH 7.4) to afford solution A. A solution of 1.48% (w/v) of polyethylenimine in phosphate buffer was prepared as solution B. The solution A and the solution B were mixed in equal volume to obtain a viscous hydrogel with a gelling time of 15 seconds and a gel burst strength of 8 kPa.

Example 8

[0039] 600 mg of an ether bond-linked benzaldehyde-terminated eight-arm polyethylene glycol (8-PEG-O-BA, M.W. 13.5K) was dissolved in 2 mL of phosphate buffer (pH 7.4) to afford solution A. A solution of 2.75% (w/v) of polylysine in phosphate buffer was prepared as solution B. The solution A and the solution B were mixed in equal volume to obtain a viscous hydrogel with a gelling time of less than 5 minutes and a gel burst strength of 2 kPa.

Example 9

[0040] 600 mg of an ether bond-linked benzaldehyde-terminated eight-arm polyethylene glycol (8-PEG-O-BA, M.W. 13.5K) was dissolved in 2 mL of phosphate buffer (pH 7.4) to afford solution A. A solution containing 2.75% (w/v) of polylysine and 1% (w/v) of polyethylenimine (M.W. 1.8K) in phosphate buffer was prepared as solution B. The solution A and the solution B were mixed in equal volume to obtain a viscous hydrogel with a gelling time of 35 seconds and a gel burst strength of 22 kPa.

Example 10

[0041] 400 mg of an ester bond-linked benzaldehyde-terminated eight-arm polyethylene glycol (8-PEG-amide-BA, M.W. 10K) was dissolved in 2 mL of phosphate buffer (pH 7.4) to afford solution A. A solution of 1.48% (w/v) of polyethylenimine (M.W. 1.8K) in phosphate buffer was prepared as solution B. The solution A and the solution B were mixed in equal volume to obtain a viscous hydrogel with a gelling time of 5 seconds and a gel burst strength of 13 kPa.

Example 11

[0042] The long-term stabilities of an ether bond-linked, amide bond-linked, and ester bond-linked benzaldehyde-terminated polyethylene glycols in an aqueous solution were compared. To shorten the test time, a basic borate buffer was selected as a solvent to compare the changes in the gelling time at different time points. 400 mg of the ether bond-linked, amide bond-linked, and ester bond-linked benzaldehyde-terminated eight-arm polyethylene glycols (M.W. 10K) were separately dissolved in 2 mL of 0.1M borate buffer (pH 9.2) to afford three solutions A. A solution of 1.48% (w/v) of polyethylenimine (M.W. 1.8K) in phosphate buffer was prepared as solution B. Each of the solutions A was mixed with the solution B in equal volume to obtain a viscous hydrogel. The three hydrogels have initial gelling times of 25 seconds, 2 seconds, and 5 seconds, respectively. The three solutions A were placed in an oven at 37° C. for 1 hour, 2 hours, 4 hours, 16 hours, 24 hours, and 40 hours, and then the differences between the gelling times after mixing with solutions B and the initial gelling times were respectively determined (as shown in FIG. 1). The results showed that the ester bond-linked polyethylene glycol lost gelling capability after 40 hours, whereas the gelling times of the ether bond-linked and the amide bond-linked benzaldehyde-terminated eight-arm polyethylene glycols were basically unchanged.