Salcaprozate sodium

Cell lines

Caco-2 cells

Preparation Method

To investigate the influence of Salcaprozate sodium on the absorption properties of rosmarinic acid, Caco-2 cell monolayer was used as an in vitro model of the gastrointestinal epithelium. To evaluate the transport, Salcaprozate sodium with rosmarinic acid (1:1) was diluted with HBSS solution to a final concentration of 200µg/mL as the test solutions. The test solution was added to the apical side of the Caco-2 cell monolayer. A 1.5mL volume of sample was taken from the basolateral side at 2h. Sample aliquots of 500µL were mixed with 500µL of methanol, shaken for 1min using a vortex mixer, and centrifuged at 8000rpm for 10min. The supernatant was injected into the HPLC system for measuring rosmarinic acid content. The apparent permeability coeffcient (Papp) was calculated according to the following equation: Papp = dQ/dt × 1/(AC₀), where dQ/dt is the permeability rate, C₀ is the initial concentration at the apical side, and A is the surface area of a monolayer. TEER was determined using a Millicell-ER system before and after membrane absorption. After membrane absorption, the cells were washed three times with HBSS solution, complete media was added for 2h or 24h, and the TEER was then determined, the cell toxicity of test drugs and regeneration of cell membrane were also investigated.

Reaction Conditions

200µg/mL; 2h

Applications

Treatment of Caco-2 cells with Salcaprozate sodium increased the apparent permeability of rosmarinic acid, without altering transepithelial electrical resistance or inducing cytotoxicity.

Animal models

Male Sprague-Dawley rats

Preparation Method

Eighteen male Sprague–Dawley (SD) rats weighing 200 ± 10g were divided into three groups: the blank control group, the group receiving Salcaprozate sodium-containing pancreatic kininogenase (PK) enteric-coated capsules, and the group receiving PK enteric-coated capsules without Salcaprozate sodium, with six rats in each group. The rats fasted but were not water-deprived 24h before the experiment, as well as during the experiment. The group with Salcaprozate sodium (Salcaprozate sodium: PK = 32:1): 4.39g of starch were precisely weighed and placed in an agate mortar. Subsequently, 5.44g of Salcaprozate sodium were added to the agate mortar, followed by the precise addition of 0.17g of PK. The group without Salcaprozate sodium: 9.83g of starch were precisely weighed and placed in an agate mortar. Meticulously weighed PK, totaling 0.17g, was added to the starch. The three groups were orally administered. At 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12h after administration, 0.3mL of blood was collected from the rat retro-orbital venous plexus using a 0.5mm capillary tube. The collected blood was stored in a 0.6mL EP tube that had been infiltrated with sodium heparin injection solution, and gently rocked up and down to prevent coagulation. The blood plasma was separated and stored at -20°C. The OD value of PK was determined using the ELISA method and substituted into the regression equation to obtain PK concentration in blood. Drug concentration-time curves were drawn using DAS 3.0 software.

Dosage form

5.44g per rat; p.o.

Applications

Salcaprozate sodium raised the plasma AUC_0-12h of PK from 4639.7 to 5679.7ng/L·h and prolonged t₁/₂ from 3.13 to 4.57h in male Sprague–Dawley rats.

References:
[1] Li Y, Yang D, Zhu C. Impact of Sodium N-[8-(2-Hydroxybenzoyl)amino]-caprylate on Intestinal Permeability for Notoginsenoside R1 and Salvianolic Acids in Caco-2 Cells Transport and Rat Pharmacokinetics. Molecules. 2018;23(11):2990.
[2] Lv Z, Luo QD, Tang ZY, et al. Synthesis of salcaprozate sodium and its significance in enhancing pancreatic kininogenase absorption performance. Pharmacol Res Perspect. 2024;12(2):e1186.