Delivery of 5-aminosalicylate to the guinea pig cecum.
Delivery of 5-aminosalicylate to the guinea pig cecum.
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将 5-氨基水杨酸盐递送至豚鼠盲肠。
DOI：
10.1016/0006-2952(87)90704-0
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发表时间：
1987
影响因子：
5.8
通讯作者：
Goldman,P
中科院分区：
文献类型：
--
作者：
Salata,K;Dull,BJ;Goldman,P
材料和方法5-ASA 是 Pharmacia Inc.（新泽西州皮斯卡塔韦）和 Rowe11 实验室（明尼苏达州鲍德特）赠送的礼物。 AC-5-ASA 和 N-丙酰基-5-ASA (Pro-5-ASA) 如前所述 [2] 合成，并通过从等份乙醇和 HzO 中重结晶纯化。雄性哈特利豚鼠购自 Charles River Breeding Laboratories (Wilmington, MA)，用豚鼠饲料 (Ralston Purina Co., St. Louis, MO) 饲养，并饲养在大鼠代谢笼 (Acme Research Products, Cleveland, OH) 中进行这些实验。动物实验。为了植入渗透泵以输注5-ASA，将雄性豚鼠（450-500g）皮下注射氯胺酮（35mg/kg）和硫酸阿托品（0.3mg/kg）预麻醉；然后用 2% 氟烷氧气溶液进行完全麻醉。通过下腹部的中线切口，暴露盲肠，并用导管（0.3 x 0.9 mm tygon 微孔管，Horton Co.，Akron，OH）刺穿其壁，并用荷包缝合线（6：0 Tevdek，Deknatel，Queens Village，NY）固定。将导管连接到2毫升容量的2 ML1 Alzet渗透泵（Alza Corp.，Palo Alto，CA）上，并将泵、导管和盲肠更换到腹膜腔中；然后用 3:6 铬肠封闭腹膜，用 3:0 丝封闭皮肤（Ethicon. Oueens Village. NY）。我们感谢 Alza 公司的 John Fara 博士为我们提供了演示该程序的录像带，并感谢哈佛动物研究中心的 Nils Lausen 博士在进行动物手术时提供了额外的指导。泵的额定输送量为 9.76、10.40 或 11.63 pl/hr，之前已装入约 2.2 g 溶液，每 g 1 M 甘氨酸缓冲液（pH 10.5）含有 67 mg 5-ASA。在某些情况下，泵装料 R&O 含有 114Clacetate 的 α 示踪剂量（52.000 玉米/e：2.36 mCi/mmol），这使得药物的输送能够根据实验结束时留在泵中的放射性标记的比例进行估计。当一组动物中使用的泵具有不同的输送速率时，出于比较的目的，将所有泵的结果标准化为单批泵的输送速率。
Materials and methods5-ASA was a gift from Pharmacia Inc.(Piscataway, NJ) and Rowe11 Laboratories (Baudette, MN). AC-5-ASA and N-propionyl-5-ASA (Pro-5-ASA) were synthesized as previously described [2] and purified by recrystallization from equal parts of ethanol and HzO. Male Hartley guinea pigs were purchased from Charles River Breeding Laboratories (Wilmington, MA), maintained on guinea pig chow (Ralston Purina Co., St. Louis, MO) and housed for these experiments in rat metabolism cages (Acme Research Products, Cleveland, OH).Animal experiments. To implant the osmotic pumps for the infusion of 5-ASA, male guinea pigs (450-500 g) were pre-anesthetized by subcutaneous ketamine (35 mg/kg) and atropine sulfate (0.3 mg/kg); full anesthesia was then obtained with 2% halothane in oxygen. Through a midline incision in the lower abdomen the cecum was exposed and its wall pierced by a catheter (0.3 x 0.9 mm tygon microbore tubing, Horton Co., Akron, OH) which was secured with a purse string suture (6: 0 Tevdek, Deknatel, Queens Village, NY). The catheter was attached to a 2-ml capacity 2 ML1 Alzet Osmotic Pump (Alza Corp., Palo Alto, CA), and the pump, catheter and cecum were replaced in the peritoneal cavity; the peritoneum was then closed with 3: 6 chromic gut and the skin with 3: 0 silk (Ethicon. Oueens Village. NY). We are indebted to Dr. John Fara of the Alza Corp. for providing us with a video tape demonstrating this procedure and to Dr. Nils Lausen of the Harvard Animal Research Center for additional guidance in performing the animal surgery. The pumps, in batches that were rated to deliver either 9.76, 10.40 or 11.63 pl/hr, had been charged previously with approximately 2.2 g of a solution that contained 67 mg of 5-ASA per g of 1 M glycine buffer, pH 10.5. In some cases, the pump charge r&o contained a-tracer amount of 114Clacetate (52.000 corn/e: 2.36 mCi/mmole) that enabled ihe delivery of drug lo bi’estimated from the proportion of radiolabel that remained in the pump at the end of the experiment. When the pumps used in a group of animals had different rates of delivery, results with all pumps were normalized to the delivery rate of a single batch of pumps for purposes of comparison.