Departamento de Química y Edafología, University of Navarra. C/ Irunlarrea s/n. 31008 Pamplona, Navarra, Spain.
Beilstein J Org Chem. 2014 Dec 24;10:3127-35. doi: 10.3762/bjoc.10.330. eCollection 2014.
All mammals lose their ability to produce lactase (β-galactosidase), the enzyme that cleaves lactose into galactose and glucose, after weaning. The prevalence of lactase deficiency (LD) spans from 2 to 15% among northern Europeans, to nearly 100% among Asians. Following lactose consumption, people with LD often experience gastrointestinal symptoms such as abdominal pain, bowel distension, cramps and flatulence, or even systemic problems such as headache, loss of concentration and muscle pain. These symptoms vary depending on the amount of lactose ingested, type of food and degree of intolerance. Although those affected can avoid the uptake of dairy products, in doing so, they lose a readily available source of calcium and protein. In this work, gels obtained by complexation of Tetronic 90R4 with α-cyclodextrin loaded with β-galactosidase are proposed as a way to administer the enzyme immediately before or with the lactose-containing meal. Both molecules are biocompatible, can form gels in situ, and show sustained erosion kinetics in aqueous media. The complex was characterized by FTIR that evidenced an inclusion complex between the polyethylene oxide block and α-cyclodextrin. The release profiles of β-galactosidase from two different matrices (gels and tablets) of the in situ hydrogels have been obtained. The influence of the percentage of Tetronic in media of different pH was evaluated. No differences were observed regarding the release rate from the gel matrices at pH 6 (t 50 = 105 min). However, in the case of the tablets, the kinetics were faster and they released a greater amount of 90R4 (25%, t 50 = 40-50 min). Also, the amount of enzyme released was higher for mixtures with 25% Tetronic. Using suitable mathematical models, the corresponding kinetic parameters have been calculated. In all cases, the release data fit quite well to the Peppas-Sahlin model equation, indicating that the release of β-galactosidase is governed by a combination of diffusion and erosion processes. It has been observed that the diffusion mechanism prevails over erosion during the first 50 minutes, followed by continued release of the enzyme due to the disintegration of the matrix.
所有哺乳动物在断奶后都会失去分解乳糖的酶（β-半乳糖苷酶）的能力，乳糖分解为半乳糖和葡萄糖。乳糖酶缺乏症（LD）的流行率在北欧人群中为 2%至 15%，在亚洲人群中几乎为 100%。在摄入乳糖后，LD 患者常出现腹痛、腹胀、痉挛和胀气等胃肠道症状，甚至出现头痛、注意力不集中和肌肉疼痛等全身问题。这些症状取决于摄入的乳糖量、食物类型和不耐受程度。虽然受影响的人可以避免摄入乳制品，但这样做会失去一种现成的钙和蛋白质来源。在这项工作中，提议使用 Tetronic 90R4 与负载β-半乳糖苷酶的α-环糊精形成的复合物凝胶作为在含有乳糖的膳食前或同时立即给药酶的方法。这两种分子都是生物相容的，可以在原位形成凝胶，并在水性介质中显示出持续的侵蚀动力学。通过 FTIR 对复合物进行了表征，该 FTIR 表明聚氧化乙烯嵌段和α-环糊精之间存在包合复合物。获得了两种不同基质（凝胶和片剂）原位水凝胶中β-半乳糖苷酶的释放曲线。评估了不同 pH 值介质中 Tetronic 百分比的影响。在 pH 6 时（t 50 = 105 min），凝胶基质的释放速率没有差异。然而，对于片剂，动力学更快，并且释放出更多的 90R4（25%，t 50 = 40-50 min）。此外，含有 25%Tetronic 的混合物释放的酶量更高。使用合适的数学模型，计算了相应的动力学参数。在所有情况下，释放数据都非常符合 Peppas-Sahlin 模型方程，表明β-半乳糖苷酶的释放受扩散和侵蚀过程的组合控制。观察到在最初的 50 分钟内，扩散机制占主导地位，随后由于基质的崩解，继续释放酶。
