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负载于氢氧化镁上的白藜芦醇(Resv@MDH)代表了一种白藜芦醇的口服制剂,与纯白藜芦醇相比,其具有更好的胃吸收和生物利用度。

Resveratrol Supported on Magnesium DiHydroxide (Resv@MDH) Represents an Oral Formulation of Resveratrol With Better Gastric Absorption and Bioavailability Respect to Pure Resveratrol.

作者信息

Iannitti Rossana Giulietta, Floridi Alessandro, Lazzarini Andrea, Tantucci Alice, Russo Roberta, Ragonese Francesco, Monarca Lorenzo, Caglioti Concetta, Spogli Roberto, Leonardi Lucio, De Angelis Massimiliano, Palazzetti Federico, Fioretti Bernard

机构信息

S&R Farmaceutici S.p.A., Perugia, Italy.

Forensic Toxicology Laboratory, CRABioN Research Center, Perugia, Italy.

出版信息

Front Nutr. 2020 Nov 13;7:570047. doi: 10.3389/fnut.2020.570047. eCollection 2020.

Abstract

Resveratrol attracts great interest because of the plethora of effects at the micromolar concentration range. Unfortunately, these effects are difficult to establish , due to the low concentration of resveratrol reached. This discrepancy is due to the molecules low solubility in water that favors the propensity for an intestinal absorption rather than in the gastric compartment. To address these challenges, we developed a Solid Dispersion of Resveratrol Supported by Magnesium Di Hydroxide formulation (Resv@MDH). This formulation displays increased water solubility and better bioavailability relative to pure resveratrol in the rabbit animal model. In our study, we evaluated the pharmacokinetics profile of resveratrol in six healthy human subjects following 180 mg of oral resveratrol administration, derived from Resv@MDH or pure resveratrol. Free resveratrol was evaluated in the whole blood sample by using HPLC - MS/MS. In comparison with pure resveratrol that displays an increase of the maximum plasma concentration, Cmax at about 90 min and 2 μM, Resv@MDH displays an earlier peak of resveratrol concentration with an increase of Cmax at about 30 min and 6 μM. The different kinetics suggest a main gastric route for resveratrol absorption from Resv@MDH, where, because of its improved dissolution rate, there seems to be a higher propensity for an acidic environment, as opposed to that with pure resveratrol. This conclusion is also supported by the numerical simulation analysis, which considers the principal steps during the oral route administration. Moreover, there is a 2-fold increase in the amount of free resveratrol with respect to pure resveratrol confirming a better bioavailability observed in the animal model. The characteristic feature of the pharmacokinetic profile of Resv@MDH implies that the beneficial properties of resveratrol in human health should be capitalized on it.

摘要

白藜芦醇因其在微摩尔浓度范围内具有多种作用而备受关注。不幸的是,由于白藜芦醇达到的浓度较低,这些作用难以确定。这种差异是由于该分子在水中的低溶解度,这有利于其在肠道而非胃腔中的吸收倾向。为应对这些挑战,我们开发了一种由氢氧化镁负载的白藜芦醇固体分散体配方(Resv@MDH)。在兔动物模型中,该配方相对于纯白藜芦醇表现出更高的水溶性和更好的生物利用度。在我们的研究中,我们评估了6名健康人类受试者口服180 mg源自Resv@MDH或纯白藜芦醇的白藜芦醇后的药代动力学特征。通过使用HPLC - MS/MS在全血样本中评估游离白藜芦醇。与在约90分钟时显示最大血浆浓度Cmax约为2 μM的纯白藜芦醇相比,Resv@MDH显示白藜芦醇浓度的峰值出现得更早,在约30分钟时Cmax增加至6 μM。不同的动力学表明,Resv@MDH中的白藜芦醇主要通过胃途径吸收,由于其溶解速率提高,与纯白藜芦醇相比,其在酸性环境中的吸收倾向似乎更高。这一结论也得到了数值模拟分析的支持,该分析考虑了口服给药过程中的主要步骤。此外,相对于纯白藜芦醇,游离白藜芦醇的量增加了两倍,证实了在动物模型中观察到的更好的生物利用度。Resv@MDH药代动力学特征的特点意味着白藜芦醇对人类健康的有益特性应加以利用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b3/8377765/3293711eae82/fnut-07-570047-g0001.jpg

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