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MMP-8 responsive intelligent periodontal drug controlled release hydrogel material and application thereof

A gel material, MMP-8 technology, applied in the treatment of periodontal disease, MMP-8 responsive intelligent periodontal drug controlled release hydrogel material field, no research that can solve MMP-8 responsiveness has been seen Report and other problems, to achieve the effect of simple drug loading method, good biocompatibility and stable activity

Active Publication Date: 2018-01-19
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the intelligent responsive controlled release system of MMPs is still blank for local lesions in the oral cavity, and there is no report on the responsiveness of MMP-8

Method used

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  • MMP-8 responsive intelligent periodontal drug controlled release hydrogel material and application thereof
  • MMP-8 responsive intelligent periodontal drug controlled release hydrogel material and application thereof
  • MMP-8 responsive intelligent periodontal drug controlled release hydrogel material and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] (1) At room temperature, using 1000 mg of chlorine resin, the sequence synthesized by Fmoc solid-phase synthesis is CGPQGIWQGC (Cys-Gly-Pro-Gln-Gly-Ile-Trp-Gln-Gly-Cys, Cysteine-Glycine-Pro Amino acid-glutamine-glycine-isoleucine-tryptophan-glutamine-glycine-cysteine) MMP-8 sensitive polypeptide (M8SP).

[0055] (2) Using mass spectrometry (ESI) to identify the synthesized polypeptide, the molecular weight is 1048, and it is confirmed that the synthesized polypeptide is the target polypeptide.

[0056] (3) Use high-performance liquid chromatography (HPLC) to detect the purity of the synthesized polypeptide, and purify the polypeptide so that the purity can reach more than 99%.

[0057] (4) Prepare a 0.3 mol / L triethanolamine (TEA) aqueous solution, adjust the pH to 8.0 with a 0.1 mol / L hydrochloric acid solution, and obtain a TEA buffer solution with a pH of 8.0.

[0058] (5) Add 20 mg of the purified M8SP into 1 ml of the above-prepared TEA buffer to obtain an M8SP so...

Embodiment 2

[0064] (1) At room temperature, using 500 mg of chlorine resin, the sequence was synthesized by Fmoc solid-phase synthesis as CGPQGIWQGC (Cys-Gly-Pro-Gln-Gly-Ile-Trp-Gln-Gly-Cys, Cysteine-Glycine-Pro Amino acid-glutamine-glycine-isoleucine-tryptophan-glutamine-glycine-cysteine) MMP-8 sensitive polypeptide (M8SP).

[0065] (2) Identify the synthesized polypeptide by mass spectrometry (ESI), and determine that the synthesized molecular weight is 1048, which is the target polypeptide.

[0066] (3) Use HPLC to detect the purity of the polypeptide, and purify the polypeptide so that the purity can reach more than 99%.

[0067] (4) Prepare a 0.3 mol / L triethanolamine aqueous solution (TEA), adjust the pH to 8.0 with a 0.1 mol / L hydrochloric acid solution, and obtain a TEA buffer solution with a pH of 8.0.

[0068] (5) Add 20 mg of the purified M8SP into 1 ml of the above-prepared TEA buffer to obtain an M8SP solution with a concentration of 20 mg / mL.

[0069] (6) Dissolve 5 mg of ...

Embodiment 3

[0076] (1) At room temperature, using 500 mg of chlorine resin, the sequence was synthesized by Fmoc solid-phase synthesis as CGPQGIWQGC (Cys-Gly-Pro-Gln-Gly-Ile-Trp-Gln-Gly-Cys, Cysteine-Glycine-Pro Amino acid-glutamine-glycine-isoleucine-tryptophan-glutamine-glycine-cysteine) MMP8-sensitive polypeptide (M8SP).

[0077] (2) ESI was used to identify the synthesized polypeptide, and it was determined that the synthesized polypeptide was the target polypeptide with a molecular weight of 1048.

[0078] (3) Use HPLC to detect the purity of the synthesized polypeptide, and purify the polypeptide to make the purity reach more than 99%.

[0079] (4) A 0.3 mol / L triethanolamine water (TEA) solution was prepared, and the pH was adjusted to 8.0 with a 0.1 mol / L hydrochloric acid solution to obtain a TEA buffer solution with a pH of 8.0.

[0080] (5) Add 20 mg of the purified M8SP into 1 ml of the above-prepared TEA buffer to obtain an M8SP solution with a concentration of 20 mg / mL.

...

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Abstract

The invention discloses an MMP-8 responsive intelligent periodontal drug controlled release hydrogel material and application thereof. A polypeptide CGPQG-IWGQC which can be specifically recognized and cut off by MMP-8 serves as a cross-linking agent, and four-arm polyethylene glycol acrylate is cross-linked to form hydrogel so as to serve as a drug controlled release carrier. According to the hydrogel, the polypeptide serving as the cross-linking agent is specifically cut off by the MMP-8 in presence of the MMP-8, the hydrogel is degraded, and drug release is realized. The designed and synthesized material is simple in preparation process, easily controllable in conditions, stable in material performance and excellent in drug controlled release effect. The material prepared by the invention can serve as the drug controlled release carrier and is widely applied to intelligent drug release of oral diseases such as periodontitis, peri-implantitis and the like. On the one hand, accurate and controlled release of the drug is realized; on the other hand, a novel solution idea or method is provided for drug tolerance encountering in clinical medicine.

Description

technical field [0001] The invention belongs to the field of chemical pharmacy, and in particular relates to an MMP-8 responsive intelligent periodontal drug controlled release hydrogel material and its application in the treatment of periodontal lesions. Background technique [0002] As one of the most common diseases of the oral cavity, periodontitis is the primary cause of tooth loss in adults and is a common disease that endangers human oral and systemic health (Sundararaj SC, et al.Biomaterials.2013; 34(34):8835- 42.). According to the current theory, periarthritis is an infectious disease with plaque biofilm as the initiating factor. Periodontal bacteria adhere and gather to release toxins, enzymes, and the body’s immune response, which cause infection and destruction of periodontal tissue. (JoshiD, et al. Drug Deliv. 2016; 23(2):363-77.), leading to periodontal pocket formation and alveolar bone resorption, ultimately resulting in tooth loss. [0003] The basic trea...

Claims

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Application Information

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IPC IPC(8): A61K47/42A61K47/14A61K31/65A61K38/38A61K9/06A61P1/02A61P31/02A61P31/04
Inventor 黄翠郭景梅喻健孙华岭杨宏业
Owner WUHAN UNIV
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