生物分子研究与治疗杂志

抽象的

需要优化时间依赖性药物输送系统来治疗胃酸疾病

PD朱亚尔

胃食管反流病 (GERD) 又称胃酸反流，是一种长期疾病，胃内容物会反流到食管，导致出现症状或并发症。[5][6] 症状包括口腔后部有酸味、胃灼热、口臭、胸痛、反流、呼吸困难和牙齿磨损。并发症包括食管炎、食管狭窄和巴雷特食管。

 

风险因素包括肥胖、怀孕、吸烟、食管裂孔疝和服用某些药物。相关药物可能包括抗组胺药、钙通道阻滞剂、抗抑郁药和安眠药。胃酸反流是由于下食管括约肌（位于胃和食管交界处）闭合不良造成的。对于使用简单措施无法改善的患者，诊断可能涉及胃镜检查、上消化道系列检查、食管 pH 监测或食管测压。

 

治疗方案包括改变生活方式、药物治疗；如果前两种方法没有改善，有时还可以进行手术。改变生活方式包括进食后三小时内不躺下、抬高床头、减肥、避免食用会引起症状的食物以及戒烟。[5] 药物包括抗酸药、H2 受体阻滞剂、质子泵抑制剂和促动力药。

 

在西方世界，有 10% 到 20% 的人口患有 GERD。偶尔出现胃食管反流但没有麻烦症状或并发症的情况更为常见。GERD 的典型症状最早于 1925 年被描述，当时 Friedenwald 和 Feldman 就胃灼热及其与食管裂孔疝的可能关系进行了评论。1934 年，胃肠病学家 Asher Winkelstein 描述了反流，并将症状归因于胃酸。

 

In recent years, many attempts have been made to enhance the drug bioavailability and therapeutic effectiveness of oral dosage forms. In this context, various gastroretentive drug delivery systems (GRDDS) have been used to improve the therapeutic efficacy of drugs that have a narrow absorption window, are unstable at alkaline pH, are soluble in acidic conditions, and are active locally in the stomach. In this review, we discuss the physiological state of the stomach and various factors that affect GRDDS. Recently applied gastrointestinal technologies such as expandable, superporous hydrogel; bio/mucoadhesive, magnetic, ion-exchange resin; and low- and high-density-systems have also been examined along with their merits and demerits. The significance of in vitro and in vivo evaluation parameters of various GRDDS is summarized along with their applications. Moreover, future perspectives on this technology are discussed to minimize the gastric emptying rate in both the fasted and fed states. Overall, this review may inform and guide formulation scientists in designing the GRDDS. The main mechanism of acid suppression by using PPI is they block the gastric H,K-ATPase, inhibiting gastric acid secretion and it produces enables healing of peptic ulcers, gastro esophageal reflux disease (GERD) Barrett’s Esophagus.

 

But it was reported that 24 hrs. Acid secretory studies suggest that maintaining the gastric acid ph. above 3 or 4 for 18 hrs. helps to 100 % duodenal ulcer healing in 4 week treatment and 100 % gastric ulcer in 8 weeks and for erosive esophagitis 20- 22hrs per day maintain the ph. above 4.[2]

 

PPI cannot inhibit all proton pumps through oral route of administration because PPI has low half-life (about 90 Min). In 24 hours again 20 % new PPI get synthesized. And mainly these newly PPI synthesized at the night time as compared to day time. So the bedtime administration of proton pump will not inhibit proton pump through nocturnal acid breakthrough. Because drug disappear after sometime. Increasing the dose of drug it does not produce any effect but split dose repeatedly produces effect.[1] So to administered dose of PPI twice a day is more effective as compared to the single large dose for maintain the ph. above 4.[2]

 

The main problem of PPI administration is to educate the people for administration of PPI to produce more effect; also compliance of patience towards the PPI is more important if for more effect dose split in twice a day patient compliance get hampered. And a chance of dose missing is more.

如果患者在夜间服用药物，那么一段时间后药物就会消失，20% 的新合成质子泵会释放胃酸，因为药物的半衰期很短，PPI 不会抑制它们。为了抑制这种新合成的质子泵，需要下一剂药物，但在夜间，患者不会依从。因此，如果新合成的药物产生酸，那么可能会出现胃反流和清晨睡眠障碍。

因此，为了克服上述问题，开发合适的药物输送系统非常重要，该系统可以在单剂量给药后输送所需的药物量。这可以抑制先前激活的PPI，也可以抑制夜间合成的PPI。

 

漏服PPI可能会使pH值再次升高至4以上，但该系统会在一段时间后释放药物，并将食管的pH值维持在3或4以下，这有助于治愈十二指肠溃疡、糜烂性食管炎。

因此设计并优化此类剂型，减少给药并发症，维持食管pH值在4以上，减少给药频率，抑制夜间PP的合成，对胃酸症的治疗，提高患者依从性，必将大有裨益。