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姜黄素β-环糊精包合物、姜黄素固体分散体和姜黄素磷脂复合物的制备、评价及在比格犬体内药代动力学比较研究。

Comparative Study of Preparation, Evaluation, and Pharmacokinetics in Beagle Dogs of Curcumin β-Cyclodextrin Inclusion Complex, Curcumin Solid Dispersion, and Curcumin Phospholipid Complex.

机构信息

College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.

Beijing Anheal Laboratories Co., Ltd., Beijing 100094, China.

出版信息

Molecules. 2022 May 7;27(9):2998. doi: 10.3390/molecules27092998.

Abstract

Curcumin is a natural acidic polyphenol extracted from turmeric with a wide range of biological and pharmacological effects. However, the application of curcumin for animal production and human life is limited by a low oral bioavailability. In this study, natural curcumin was prepared for the curcumin β-cyclodextrin inclusion complex (CUR-β-CD), curcumin solid dispersion (CUR-PEG-6000), and curcumin phospholipid complex (CUR-HSPC) using co-precipitation, melting, and solvent methods, respectively. Curcumin complex formations were monitored using scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR) techniques via the shifts in the microscopic structure, molecular structure, and crystalline state. Subsequently, twenty-four female beagle dogs were randomly divided into four groups to receive unmodified curcumin and three other curcumin preparations. The validated UPLC-MS assay was successfully applied to pharmacokinetic and bioavailability studies of curcumin in beagle dog plasma, which were collected after dosing at 0 min (predose), 5 min, 15 min, 30 min, 40 min, 50 min, 1.5 h, 3 h, 4.5 h, 5.5 h, 6 h, 6.5 h, 9 h, and 24 h. The relative bioavailabilities of CUR-β-CD, CUR-PEG-6000, and CUR-HSPC were 231.94%, 272.37%, and 196.42%, respectively. This confirmed that CUR-β-CD, CUR-HSPC, and especially CUR-PEG-6000 could effectively improve the bioavailability of curcumin.

摘要

姜黄素是从姜黄中提取的一种天然酸性多酚,具有广泛的生物学和药理学作用。然而,由于其口服生物利用度低,限制了其在动物生产和人类生活中的应用。本研究采用共沉淀法、熔融法和溶剂法分别制备天然姜黄素的姜黄素-β-环糊精包合物(CUR-β-CD)、姜黄素固体分散体(CUR-PEG-6000)和姜黄素磷脂复合物(CUR-HSPC)。通过微观结构、分子结构和晶体状态的变化,利用扫描电子显微镜(SEM)、X 射线衍射(XRD)和傅里叶变换红外(FT-IR)技术监测姜黄素复合物的形成。随后,将 24 只雌性比格犬随机分为 4 组,分别给予未修饰的姜黄素和其他 3 种姜黄素制剂。建立的 UPLC-MS 测定方法成功应用于比格犬血浆中姜黄素的药代动力学和生物利用度研究,分别于给药后 0 min(预给药)、5 min、15 min、30 min、40 min、50 min、1.5 h、3 h、4.5 h、5.5 h、6 h、6.5 h、9 h 和 24 h 采集血样。CUR-β-CD、CUR-PEG-6000 和 CUR-HSPC 的相对生物利用度分别为 231.94%、272.37%和 196.42%。这证实了 CUR-β-CD、CUR-HSPC,特别是 CUR-PEG-6000 可以有效提高姜黄素的生物利用度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7242/9102399/40539182ede0/molecules-27-02998-g001.jpg

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