| The accumulation of retinal for its circulatory disturbance leads to retinal cell poisoned and then causes some retinopathy.5-aminosalicylic acid is a kind of medicine for treating enteritis and it is found that it can treat retinopathy by the formation of Schiff base with retinal.5-aminosalicylic acid has a short half-life, but its half-life can be prolonged and achieves a goal of sustained release drug delivery when it is formed into Schiff base with aldehydes and then slowly decomposed in the retinal cells. However Schiff bases formed by 5-aminosalicylic acid and aldehydes have poor solubility in water. Therefore, it is necessary to improve their water solubility in order to achieve the aim of drug injection for treating retinopathy.In this paper, we first studied the differences of the decomposition rate under physiological pH of Schiff base formed by 5-aminosalicylic acid and aldehydes which contain different types of substituents and steric hindrance. The influences on the decomposition rate of the Schiff bases by the electron withdrawing group, electron donating group or steric hindrance of the aldehyde molecules is defined. These provide guidances for the synthesis of the sustained release Schiff base system. Then we studied the Schiff base’s solubility in water and decomposition rules after it modified by small hydrophilic molecular, formed into inclusion or conjugated with Beta cyclodextrin. Thus we find appropriate methods to improve the water solubility of the sustained-release 5-aminosalicylic acid’s Schiff base system.Firstly we synthesized different Schiff bases with 5-aminosalicylic acid and salicylaldehyde compounds, which contain electron withdrawing group (nitryl) or electron donating group (methyl) or steric hindrance, while the structures of them were characterized by means of 1H-NMR. The influence of different groups and steric hindrance on the decomposition rate of Schiff base C=N bond was studied by UV. It was found that the synthesis of Schiff base from aldehyde compounds, aromatic aldehydes with ring containing electron withdrawing group or steric hindrance can slow down the decomposition rate of the Schiff base to some extend while the aldehyde containing electron donating group promotes the decomposition rate.With using biocompatible triethylene glycol to modify the Schiff base, we synthesized the Schiff base modified by triethylene glycol. And its structure was characterized by 1H-NMR and IR. Sustained release effect of the modified Schiff base was evaluated by UV detection, indicating that the decomposition rate of the Schiff base will speed up with incrasing its solubility in water.Cyclodextrin is widely used in the inclusion of lipid drugs to increase their water solubility. In this paper, the grinding method was used to make cyclodextrin inclusion of Schiff base, and the included compound was characterized by IR, DSC and water solubility. Analysis of UV confirmed that the inclusion rate was the highest at the guest/host ratio of 1.5-2. The results showed that the cyclodextrin inclusion method significantly improved the water solubility of Schiff base.The cyclodextrin conjugated compound was formed by conjugation of Schiff base with cyclodextrin, and was characterized by IR and UV. Since the cyclodextrin has good water solubility, we hope that it can replace the silsesquioxane mentioned in the reference as a Schiff base carrier, and make the Schiff base a good solubility and also a slower release system. UV anslysis of the sustained release effect of the Schiff base showed that the Schiff base conjugated with cyclodextrin had a sustained release effect better than the free Schiff base. The results indicate that the study of the cyclodextrin conjugated sustained-release system has a good prospect.The studies above not only provide a reference for the construction of 5-aminosalicylic acid’s Schiff base slow release system but also solve a part problems for the researches on the slow release drug system of 5-aminosalicylic acid’s Schiff base to treat retinopathy in the future. |
PDF Full Text Request