| Curcumine is an effective component extracted from curcumae longae, it has many pharmacutical activities and less toxicity, which lead to good clinical application potentiality. Recent studies suggect that curcumine will be metabolized quickly after injected though having good antineoplasmic activity in vitro, this is related to its low water solubility,stability and bioavailability. Therefore people tried to overcome these shortcomings of curcumine by various approaches, for example, changing the dosage form; reforming its structure; mixing it with other drugs to get new mixture... in spite of some achievement, the achivement was limited.Prodrug designing principle claims that new compounds, the prodrug, should be formed by introducing drugs to some innocuities by covalent bonds, when arrive in the active place, the temporary transport groups splite, and release active compoud and finally educe the pharmacologic action. This can avoid drug losing efficacy before it arrives destination, Illuminated from it, we prepared curcumine prodrug bonded with polyethylene glycol by systhesis, and had tackled its water solubility distinguishly, the specific performances are as follow:1. Prepare curcumine prodrug by chemosythesis: The terminal hydroxyl group of PEG was changed into carboxylic acid with the introduction of succinic acids. The product was activated with dicyclohexyl carbondimide (DCC) and p-nitrophenol to form an active ester. Amino acids were introduced into molecular skeleton of PEG through functionalization to give PEG-DA-Pro. Esterification of-OH of curcumin with PEG-DA-Pro produced curcumine derivant.2. Purify the product by gel-filtration chromatography, then confirm the chemical constitution of curcumine prodrug by determining its melting point, analysis its behavior by UV,IR,MS and NMR.3. Study the physico-chemical property of curcumine prodrug, such as its drug carrying quantity and water solubility. Resuslts show that the solubility was improved by 100 times. |
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