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A kind of synthetic method of dopamine derivative modified by cyclodextrin

A synthesis method and cyclodextrin technology, which is applied in the direction of pharmaceutical formulations, organic active ingredients, medical preparations of non-active ingredients, etc., can solve the problem of low drug loading, easy uneven deposition, difficult to achieve drug immobilization, controlled release or Sustained release and other issues to achieve the effects of slowing down the polymerization rate, weakening uneven sedimentation, and achieving degradable properties

Active Publication Date: 2021-05-18
JIANGNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, although dopamine has many advantages in surface modification of materials after self-polymerization, polydopamine is prone to uneven deposition in an alkaline environment (pH 8.5, seawater alkalinity) and oxygen participation, forming a rigid and brittle material. membrane material
In addition, in improving the functionalization of tissue engineering scaffolds, it is often necessary to immobilize drugs or growth factors on the surface of biomaterials. However, most common drugs are oil-soluble materials, which are difficult to combine with hydrophilic polydopamine, so it is difficult to achieve drug immobilization, controlled or sustained release
Moreover, the current dopamine polymer assembly still has the disadvantage of low drug loading as a delivery system for hydrophobic drugs.

Method used

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  • A kind of synthetic method of dopamine derivative modified by cyclodextrin
  • A kind of synthetic method of dopamine derivative modified by cyclodextrin
  • A kind of synthetic method of dopamine derivative modified by cyclodextrin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Synthesis of mono-6-deoxy-dopamine cyclodextrin (β-CD-6-DA):

[0030] Dissolve β-cyclodextrin (β-CD) (17.0g, 15.0mmol) in 200mL of 1% NaOH solution, and add 15mL of p-toluenesulfonyl chloride (4.0g, 22.5mmol) dropwise at 0°C ) in acetonitrile solution, stirred and reacted at 25°C for 2h, then filtered, adjusted to pH 2 with hydrochloric acid, kept at 4°C overnight, a large amount of precipitates precipitated, filtered, and the solid was recrystallized 3 times to obtain a white solid, dried in vacuo at 40°C for 5h, to obtain Mono 6-p-toluenesulfonyl cyclodextrin, spare.

[0031] Take 1.00g (0.78mmol) of mono-6-p-toluenesulfonyl cyclodextrin, 0.80g (4.22mmol) of dopamine hydrochloride, add catalyst DMAP (4-dimethylaminopyridine) to 0.19g (1.5mmol), KI (potassium iodide) was 0.06g (0.4mmol), repeatedly evacuated and filled with nitrogen, then injected 10mL of anhydrous DMF (N,N-dimethylformamide) and 1mL of anhydrous methanol into the needle, dissolved the solid sample un...

Embodiment 2

[0034]Take 1.30g (1mmol) of mono-6-p-toluenesulfonyl cyclodextrin, 1.9g (10mmol) of dopamine hydrochloride, add catalyst DMAP to 0.22g (1.8mmol), KI to 0.06g (0.4mmol), repeatedly vacuumize and fill Nitrogen, then inject 13mL of anhydrous DMF and 1.3mL of anhydrous methanol into the needle, dissolve the solid sample under stirring, adjust the pH to 6.8, react at 100°C for 12h, concentrate the obtained reaction mixture, dry silica gel powder column, the eluent volume ratio is n-butanol: acetic acid: water = 12:1:1, and the cyclodextrin-modified dopamine derivative (β-CD-6-DA) is obtained by column chromatography elution, producing The rate is 78.9%.

[0035] (1) On the basis of Example 2, explore the influence of the reaction molar ratio of mono-6-p-toluenesulfonyl cyclodextrin and dopamine hydrochloride on the yield of the reaction product. The results are shown in Table 1.

[0036] The influence of table 1 reaction system substrate molar ratio on product yield

[0037]

...

Embodiment 3

[0048] Oxidative self-polymerization of β-CD-6-DA:

[0049] Take 0.5 g of β-CD-6-DA prepared in Example 2, place it in a weakly alkaline aqueous solution with pH 8.5, stir it in the air for 48 hours, then distill it under reduced pressure to remove water, freeze-dry it, and test the high-resolution mass spectrum, see attached figure 1 . from figure 1 It can be seen that the molecular mass of 1308.3 of the original β-CD-6-DA has disappeared, and the system mainly presents the proton peak with a molecular weight of 1306.4212. This is because the two phenolic hydroxyl groups on β-CD-6-DA are oxidized to two The molecular weight reduction caused by quinone further proves that after dopamine is modified by large molecular weight cyclodextrin, in an alkaline environment, dopamine is not generated as a large amount of polydopamine particles as reported in the literature, but only phenolic hydroxyl groups are oxidized. That is, excessive oxidation of β-CD-6-DA did not occur.

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Abstract

The invention discloses a method for synthesizing cyclodextrin-modified dopamine derivatives. Pyridine and potassium iodide are used as catalysts, vacuumize the reaction system to reach an anhydrous and anaerobic state; then add anhydrous N,N-dimethylformamide and anhydrous methanol respectively, stir, dissolve the solid sample, adjust the pH to weak acidity, and place React at 80-100°C for 12-24 hours to obtain a reaction mixture, perform rotary evaporation to remove the solvent, and elute through column chromatography to obtain a mono-6-deoxy-dopamine cyclodextrin derivative. The cyclodextrin-modified dopamine derivative synthesized by the present invention reduces the problem of uneven sedimentation of polydopamine on the surface of the material, has the excellent performance of realizing degradable performance in the living body, and overcomes the difficulty of combining oil-soluble pharmaceutical materials with hydrophilic ones. The combination of polydopamine makes it difficult to achieve drug fixation and sustained release.

Description

technical field [0001] The invention relates to the field of carbohydrate synthesis, in particular to a method for synthesizing cyclodextrin-modified dopamine derivatives. Background technique [0002] Cyclodextrin (CD for short) is a general term for a series of cyclic oligosaccharides produced by amylose under the action of cyclodextrin glucosyltransferase produced by Bacillus, usually containing 6 to 12 D-pyrans glucose unit. [0003] Dopamine (DA) is very similar to L-3,4-dihydroxyphenylalanine (DOPA) in the adhesion proteins (mytilus foot proteins, MAPs) MAP1 to MAP6 secreted by mussel foot glands. The structure retains the bisphenol functional group of dopamine and the amino terminal functional group of lysine. Because the bisphenol functional group contained in dopamine can form a covalent or non-covalent bond with the surface of the substrate material, it has super strong adhesion properties. Compared with traditional adhesive bio-based materials such as polyuretha...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08B37/16C08G83/00A61K31/355A61K47/34A61K47/69C03C17/28
Inventor 杨成张冬梅
Owner JIANGNAN UNIV
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