Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
19 巻 , 12 号
選択された号の論文の18件中1~18を表示しています
  • Michinao MIZUGAKI, Kunihiko ITOH, Takahumi YAMAGUCHI, Shunji ISHIWATA, ...
    1996 年 19 巻 12 号 p. 1537-1540
    発行日: 1996/12/15
    公開日: 2008/04/10
    ジャーナル フリー
    A monoclonal antibody specific for a modified nucleoside, 5-methyl-2'-deoxycytidine (m5dCyd), was prepared using 5-methylcytidine (m5Cyd)-keyhole limpet haemocyanin (KLH) conjugate, and was characterized. Termed FMC9, the antibody reacts with m5dCyd and slightly with m5Cyd and 5-methylcytosine (m5Cyt) but not with other nucleosides tested in this investigation. FMC-9 was used in an enzyme-linked immunosorbent assay (ELISA) system for the quantitation of m5dCyd levels. Sensitivity was in the picomole range. Methylation levels in peripheral blood cells of healthy donors were determined by inhibition ELISA. The percentage of m5dCyd in peripheral blood cells of 10 healthy donors was 5.08±0.50%. These results suggest that the inhibition ELISA using FMC9 is useful to monitor m5dCyd levels in the peripheral blood cells.
  • Yusuke MURAKAMI, Tsukasa SEYA, Mitsue KURITA, Shigeharu NAGASAWA
    1996 年 19 巻 12 号 p. 1541-1545
    発行日: 1996/12/15
    公開日: 2008/04/10
    ジャーナル フリー
    We isolated a 1257-bp cDNA encoding a membrane cofactor protein (MCP, CD46)/measles virus (MV) receptor-like protein from a cDNA library of Vero cells, in which wild MV strains were established. Vero cells contain MCP mRNA splice products encoding different cytoplasmic tails like human cells. The deduced amino acid sequence of the cDNA was 86% identical to that of human MCP. Vero cell MCP expressed on CHO cells was recognized by monoclonal antibodies against human MCP, and served as a potent MV receptor. In addition, Vero MCP was as effective as human MCP in human factor I-mediated C3b cleavage. Thus, the high MV susceptibility of Vero cells can in part be attributed to an MCP-like molecule that is structurally and functionally similar to human MCP.
  • Il-Sung JANG, Dong-Hyun KIM
    1996 年 19 巻 12 号 p. 1546-1549
    発行日: 1996/12/15
    公開日: 2008/04/10
    ジャーナル フリー
    An α-L-rhamnosidase (EC 3.2.1.40) was purified 1500-fold from Bacteroides JY-6, an intestinal anaerobic bacterium of human. The specific activity of purified enzyme was 89.9 μmol/min/mg protein. The enzyme (M.W.240000) is composed of two subunits of M.W. 120000 with pI and optimal pH values of 4.2 and 7.0, respectively.The apparent Kms for naringin, rutin and p-nitrophenyl-α-L-rhamnopyranoside were determined to be 0.89, 1.44 and 0.29 mM, respectively. The enzyme was strongly inhibited by L-rhamnose, L-fucose, saccharic acid 1, 4-lactone, p-chlormercuriphenylsulfonic acid and Pb2+.
  • Tsunetomo TAKEI, Yohichi HASHIMOTO, Eiji OHTSUBO, Kaoru SAKAI, Hiroshi ...
    1996 年 19 巻 12 号 p. 1550-1555
    発行日: 1996/12/15
    公開日: 2008/04/10
    ジャーナル フリー
    A series of novel amphipathic peptides constituted of an N-terminal hydrophilic portion (CPVHLKR, residues 6-12) of human pulmonary surfactant protein-C (SP-C) and a poly-leucine (poly-L) stretch of various chain lengths as the C-terminal hydrophobic tail were synthesized and evaluated relevant to their ability to improve the surface activity of a ternary lipid mixture composed of dipalmitoylphosphatidylcholine, egg-phosphatidylglycerol and palmitic acid (DPPC/E-PG/PA, 75 : 25 : 10, w/w) in a Langmuir-Wilhelmy surface balance. CPVHLKRL11, a human SP-C analogue bearing an 11-residue poly-L tail, and its related peptides with longer tails in the ternary lipid mixture, accelerated not only the surface spreading at the air-water interface but also exhibited significantly improved dynamic surface activity, compared to the ternary lipid mixture. Their surface activities were almost indiscernible from those of the synthetic human SP-C. When reconstituted into a ternary lipid mixture containing members of the homologous series of n-saturated diacylphosphatidylglycerol, the surface activities of the poly-L analogues were almost completely unaffected, whereas replica peptides carrying the hydrophobic portion of native SP-C were found to have distinct surface activities depending upon the acyl-chain lengths of phosphatidylglycerol. The poly-L stretch of a poly-L analogue could be replaced with poly-norleucine of the same chain length without a significant loss of surface activity.Substitution of the poly-L portion in the analogues with poly-valine or poly-isoleucine resulted in a considerable decrease in surface activity. The poly-L analogue in the DPPC/E-PG/PA mixture was demonstrated to act as an excellent surfactant comparable with Surfactan[○!R], a modified bovine surfactant preparation that was used for treatment for infant respiratory distress syndrome, based on evaluation of the lung pressure-volume characteristics using premature rabbit neonates.
  • Hiroki MIZUGUCHI, Naomi KUDO, Yoichi KAWASHIMA
    1996 年 19 巻 12 号 p. 1556-1559
    発行日: 1996/12/15
    公開日: 2008/04/10
    ジャーナル フリー
    The relative contribution of stearoyl-CoA desaturase and 1-acylglycerophosphocholine (1-acyl-GPC) acyltransferase, which are induced by peroxisome proliferators, to the increase in the proportion of oleic acid in C-2 position of phosphatidylcholine (PtdCho) in the liver of rats was investigated. Rats were administered either 4-chlorophenoxyisobutyric acid (clofibric acid), 2, 2'-(decamethylenedithio)-di-ethanol (tiadenol) or perfluorooctanoic acid in varying doses. With administration of these peroxisome proliferators, the proportion of oleic acid in C-2 position of PtdCho in hepatic microsomes was increased in commensurate with the increase in activities of stearoyl-CoA desaturase and 1-acyl-GPC acyltransferase. Multiple regression analysis revealed that although there is a high correlation among the three parameters examined, the partial correlation between the proportion of oleic acid in the C-2 position and the activity of stearoyl-CoA desaturase is significantly higher than that between the proportion of oleic acid in the C-2 position and the activity of 1-acyl-GPC acyltransferase. The contribution of stearoyl-CoA desaturase to the increase in the proportion of oleic acid in the C-2 position thus appears greater than that of 1-acyl-GPC acyltransferase.
  • Kazuto OHKURA, Hiroshi TERADA
    1996 年 19 巻 12 号 p. 1560-1564
    発行日: 1996/12/15
    公開日: 2008/04/10
    ジャーナル フリー
    The regulation of intracellular pH (pHi) was examined in newborn rat skin basal cells. When basal cells were acid-loaded by externally applied weak acid or by pretreatment with NH+4, the pHi recovered toward its resting value. This recovery was accompanied by Na+ influx and H+ efflux. The recovery of pHi and concomitant Na+/H+ fluxes were reversibly inhibited by amiloride. Other ionic flux inhibitors 4, 4'-diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS) and furosemide slightly inhibited the pHi recovery from an acid load. The recovery rate from an acid load depended on the concentration of the external Na+. Li+ could substitute for Na+ in the pHi recovery, but K+ had no effect on the recovery.The keratin synthesis of basal cells was decreased by amiloride, and this decrement was deduced to be due to the acidification of the intracellular space. Although ascorbic acid had no effect on the pHi recovery of basal cells, it enhanced the keratin synthesis of the cells. Moreover, an inhibitor of the collagen synthesis, cis-hydroxyproline, suppressed the keratin synthesis but had no effect on the pHi recovery. We therefore believe that the keratin synthesis of the cells was also regulated by the environment, which was formed by the synthesized collagen.Thus, the pHi in the skin basal cells was regulated by the amiloride-sensitive exchange system, and this system seems to be involved in the keratin synthesis.
  • Yasuhiro NODA, Naoaki SHIMIZU, Yutaka KAWAZOE
    1996 年 19 巻 12 号 p. 1565-1569
    発行日: 1996/12/15
    公開日: 2008/04/10
    ジャーナル フリー
    The permeability of murine leukemia L1210 cells toward non-permeant fluorescent Lucifer Yellow (LY) was evaluated by flow cytometry following vortex-stirring of cells with LY in the presence of high molecular weight polyacrylic acid (A-119). Permeabilization by this technique was greatly enhanced in growth phase cells, whereas it was appreciably reduced in resting cells which had been maintained in unchanged culture medium for 2 to 4 d.This reduction in permeabilization of resting cells gradually disappeared when resting cells were re-suspended in fresh culture medium, and the degree of permeabilization was restored to that of the growing cells. It is recommended that the mammalian cells used for internalization of non-permeant materials by vortex-stirring with A-119 should be in the early log phase.
  • Kazuhiko TSUTSUMI, Yasuhide INOUE, Chieko YOSHIDA
    1996 年 19 巻 12 号 p. 1570-1573
    発行日: 1996/12/15
    公開日: 2008/04/10
    ジャーナル フリー
    Diabetic cataracts are thought to be caused by hyperglycemia associated with disturbed glucose metabolism.Diabetes mellitus often involves abnormal lipid metabolism in addition to abnormal glucose metabolism. To date, however, very few studies have counted hyperlipidemia as a risk factor for diabetic cataracts. The present study was undertaken to determine whether this actually is a risk factor for diabetic cataracts and to confirm that the onset of cataracts associated with diabetes mellitus can be suppressed by correction of hyperlipidemia.When rats with streptozotocin (STZ)-induced diabetes mellitus were fed an ordinary diet, cataracts became evident at 9 weeks in 26.7% of animals, and increased to an incidence of 73.3% after 10 weeks of STZ treatment.However, in rats with STZ-induced diabetes mellitus that were fed a cholesterol rich diet to induce severe hyperlipidemia, cataracts were observed one week earlier, after 8 weeks of treatment, in 36.0% of animals, with an increase to a 52.0% incidence and a 76.0% incidence after 9 and 10 weeks of STZ treatment, respectively.Hyperlipidemia was therefore associated with an earlier onset and an elevated incidence of diabetic cataracts. When the lipoprotein lipase (LPL) activator NO-1886 was administered to diabetic rats which had developed severe hyperlipidemia, they showed a decrease in plasma total cholesterol, triglyceride and non-high density lipoprotein (non-HDL)-cholesterol levels and an increase in high density lipoprotein (HDL)-cholesterol level, and the onset of diabetic cataracts was markedly suppressed. The results of this study suggest that hyperlipidemia and low HDL-cholesterol levels may be risk factors for the onset of diabetic cataracts, and that this onset can be suppressed if measures are taken to alleviate these risk factors. The LPL activator NO-1886 may be useful in preventing the onset of diabetic cataracts.
  • Koichi KAWASAKI, Mitsuko MAEDA, Sachiye INOUE, Yuko YAMASHIRO, Yoshihi ...
    1996 年 19 巻 12 号 p. 1574-1579
    発行日: 1996/12/15
    公開日: 2008/04/10
    ジャーナル フリー
    Peptides (H-Glu-Ile-Leu-Asp-Val-NH2, H-Glu-Ile-Leu-Asp-Val-Pro-Ser-Thr-NH2, H-Arg-Glu-Asp-Val-NH2) and their poly(ethylene glycol)(PEG) hybrids related to the core sequence of the type III connecting segment domain of fibronectin A chain were prepared by the solution method or the solid phase method. Their inhibitory effects on the adhesion and migration of B16-BL6 melanoma cells to fibronectin were assessed in vitro, and their therapeutic potency against tumor metastasis were also examined. Anti-adhesive and anti-migrative effects of the synthetic fibronectin-related peptids were superior to those of their PEG hybrids, so we found that the in vitro bioactivity of peptides decreased by PEGylation. In the in vivo assay, we found that the synthetic peptides containing Glu-Ile-Leu-Asp-Val and Arg-Glu-Asp-Val sequences exhibited an inhibitory effect on the experimental metastasis of B16-BL6 melanoma. Of the synthetic peptides, H-Glu-Ile-Leu-Asp-Val-NH2 exhibited the most potent inhibitory effect. Hybrid formation of Arg-Glu-Asp-Val with poly(ethylene glycol) resulted in potentiation of the inhibitory effect of the parent peptides. A mixture composed of PEG hybrids of Glu-Ile-Leu-Asp-Val, Arg-Glu-Asp-Val and Tyr-Ile-Gly-Ser-Arg dramatically inhibited tumor metastasis.
  • Quanbo XIONG, Shigetoshi KADOTA, Tadao TANI, Tsuneo NAMBA
    1996 年 19 巻 12 号 p. 1580-1585
    発行日: 1996/12/15
    公開日: 2008/04/10
    ジャーナル フリー
    The acetone-H2O (9 : 1) extract from the stem of Cistanche deserticola showed a strong free radical scavenging activity. Nine major phenylethanoid compounds were isolated from this extract. They were identified by NMR as acteoside, isoacteoside, 2'-acetylacteoside, tubuloside B, echinacoside, tubuloside A, syringalide A 3'-α-rhamno-pyranoside, cistanoside A and cistanoside F. All of these compounds showed stronger free radical scavenging activities than α-tocopherol on 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical and xanthine/xanthine oxidase (XOD) generated superoxide anion radical (O&minusou;2). Among the nine compounds, isoacteoside and tubuloside B, whose caffeoyl moiety is at 6'-position of the glucose, showed an inhibitory effect on XOD. We further studied the effects of these phenylethanoids on the lipid peroxidation in rat liver microsomes induced by enzymatic and non-enzymatic methods. As expected, each of them exhibited significant inhibition on both ascorbic acid/Fe2+ and ADP/NADPH/Fe3+ induced lipid peroxidation in rat liver microsomes, which were more potent than α-tocopherol or caffeic acid.The antioxidative effect was found to be potentiated by an increase in the number of phenolic hydroxyl groups in the molecule.
  • Masaki OGATA, Yukisumi IIZUKA, Ryo MURATA, Noboru HIKICHI
    1996 年 19 巻 12 号 p. 1586-1590
    発行日: 1996/12/15
    公開日: 2008/04/10
    ジャーナル フリー
    We studied the effect of diabetes on the pharmacokinetics of cyclosporin A (CyA) after intravenous and oral administration of CyA using the plasma and lymph of streptozotocin (STZ)-induced diabetic rat. There were no significant differences in the systemic and lymphatic availabilities after intravenous administration of CyA in diabetic rats compared with those of the controls. On the other hand, systemic and lymphatic availabilities after oral administration of CyA were significantly different in diabetic rats compared to those in the controls. These results suggest that the pharmacokinetics of CyA, particularly absorption, were altered in diabetic rats. Gastrointestinal transit in diabetic rats was also studied. The gastric emptying rate in diabetic rats was enhanced compared with that of the controls, but small intestinal transit was reduced in diabetic rats, suggesting that a change in gastro-intestinal transit in diabetic rats may influence the absorption of CyA.The increased absorption of CyA from the digestive tract of diabetic rats altered not only the systemic availability but also the lymphatic availability, suggesting that altered systemic availability may cause adverse effects and that altered lymphatic availability may influence the immunosuppressive effects.
  • Yorinobu MAEDA, Toshio KONISHI, Kei OMODA, Yoshiaki TAKEDA, Shinji FUK ...
    1996 年 19 巻 12 号 p. 1591-1595
    発行日: 1996/12/15
    公開日: 2008/04/10
    ジャーナル フリー
    We report a case of side effects caused by the increase in plasma theophylline concentration after coadministration of aciclovir had been started during theophylline therapy. Interaction between theophylline and aciclovir has not previously been reported. Therefore, a study of the pharmacokinetic and metabolic interactions between theophylline and aciclovir was carried out in five healthy male volunteers. All subjects received a single oral dose of 320 mg theophylline (aminophylline, 400 mg) after they had taken oral aciclovir 800 mg five times daily for two consecutive days. The area under the curve from 0 to infinity of theophylline (AUC0-∞) after coadministration of aciclovir was increased from 189.9±18.2 to 274.9±34.3 μg·h/ml (p<0.01), and total body clearance was decreased from 28.4±2.9 to 19.8±2.5 ml/h/kg (p<0.01). Further, there was a significant increase in urinary theophylline and decreases in urinary 1, 3-dimethyluric acid and 1-methyluric acid after coadministration of aciclovir. The decrease in total body clearance is likely to have resulted from inhibition of metabolism via the oxidation pathway.The results indicated that with aciclovir therapy lower doses of theophylline might be necessary and careful monitoring of plasma concentrations was essential.
  • Hitoshi SATO, Ya Min WANG, Isao ADACHI, Isamu HORIKOSHI
    1996 年 19 巻 12 号 p. 1596-1601
    発行日: 1996/12/15
    公開日: 2008/04/10
    ジャーナル フリー
    This study describes the pharmacokinetic behaviors of taxol after intravenous administration of taxol-loaded poly(lactic-co-glycolic acid) microspheres containing isopropyl myristate (namely, Taxol-IPM-PLGA-MS) and taxol saline solution to mice. Taxol-IPM-PLGA-MS were prepared using a solvent evaporation technique. The drug content and trapping efficiency of taxol in the microspheres were 5.09% (w/w) and 98%, respectively; the average diameter of the microspheres was 30.1 μm. Scanning electron microscopy showed that Taxol-IPM-PLGA-MS were spherical with a smooth surface. After administration of the drug saline solution (3 mg taxol/kg), taxol disappeared rapidly from plasma within 4-6 h and distributed extensively in various tissues. The tissue levels and AUCfinite of taxol in the lung were obviously higher than those in plasma but relatively lower than those in kidneys, bile, and liver. The biodistribution of taxol after administration of Taxol-IPM-PLGA-MS (3 mg taxol/kg), on the other hand, was altered significantly from the control (taxol solution) group. No taxol was detected in plasma or bile within 3 weeks, and only very low level of taxol was detected in the kidneys or liver within 48 h. However, taxol concentrations in the lung were increased significantly with the microsphere group; the peak concentration of taxol and AUCfinite in the lung was three times and 500 times higher than those with the taxol solution group, respectively.It was also noticed that the taxol levels in the lung were maintained at relatively high levels (>10 μg/ml) for 3 weeks. Thus, the present study demonstrated the effective targeted delivery of taxol to the lung of mice using Taxol-IPM-PLGA-MS.
  • Byong-Lyul LIE, Akiyo IWAHORI, Ruriko SAMPE, Yukiko HIROTA, Yasushi TS ...
    1996 年 19 巻 12 号 p. 1602-1606
    発行日: 1996/12/15
    公開日: 2008/04/10
    ジャーナル フリー
    We have synthesized four kinds of reversed peptides of various physiologically active peptides, which inhibit TNF (tumor necrosis factor) cytotoxicity, produce NGF (nerve growth factor), exert antimicrobial activity and inhibit cell attachment, respectively. They were examined for their biological activity in comparison with that of normal peptides, that is, naturally occurring peptides. The reversed peptides induce similar activities, but to a lesser extent than those of the normal peptides, respectively. These results indicate that there may be conformationally ambiguous binding in some of the naturally occurring ligand-protein interactions. This method may be useful as a tool to rapidly generate a novel lead peptide with the desired biological function from a naturally occurring active peptide.
  • Youji OKADA, Michikazu KANEKO, Haruo OKAJIMA
    1996 年 19 巻 12 号 p. 1607-1610
    発行日: 1996/12/15
    公開日: 2008/04/10
    ジャーナル フリー
    As a part of our work on the antioxidant properties of naturally occurring furan fatty acids (F acids), we evaluated their hydroxyl radical (HO·) scavenging activity by an electron spin resonance (ESR) spin trapping technique with 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO). The additions of F acids to the incubation mixture of Fe2+-diethylenetriaminepentaacetic acid complex, H2O2 and DMPO decreased the intensity of the DMPO-OH adduct signal in a dose-dependent way. This decrease was not attributed to the destruction of DMPO-OH adduct by F acids. Kinetic competition studies indicated that the decrease in DMPO-OH signal intensity was mainly due to the competition of F acids with DMPO for HO·, and not to the inhibition of the HO· generation system itself.F acids were found to react rapidly with HO· at approximately a diffusion-controlled rate (1.7×1010M-1s-1).Comparison with the common HO· scavengers indicated that the rate constant of F acids is higher than those of mannitol and ethanol, and is compatible with those of histidine and dimethylsulfoxide, demonstrating that F acids are a potent HO· scavenger. It is suggested that F acids may serve as antioxidants in biological systems through their ability to scavenge HO·.
  • Masaaki Nomura, Norihiko SUGIURA, Ken-ichi MIYAMOTO
    1996 年 19 巻 12 号 p. 1611-1613
    発行日: 1996/12/15
    公開日: 2008/04/10
    ジャーナル フリー
    Rat ascites hepatoma AH66F is a high malignant tumor line, and AH66F-bearing rats died about 10 d after tumor inoculation. When treated with a protein kinase C (PKC) inhibitor, NA-382, the life span of AH66F-bearing rats was significantly prolonged, while a potent protein kinase A inhibitor, H-89, was not effective. In the adhesion assay, the adhesive ability to the mesentery-derived mesothelial cells (M-cells) of AH66F cells from rats injected with 10 mg/kg of NA-382 was significantly decreased, while the adhesion rate of the cells from the vehicle control group and from the H-89 (10 mg/kg)-treated group was about 50%. The adhesion of AH66F cells from the vehicle control group was curtailed to one half by leukocyte function-associated antigen-1 (LFA-1) β-chain monoclonal antibody (WT.3), but that from the NA-382 group was not further influenced by WT.3. In flow cytometric analysis using WT.3, the expression of LFA-1 β-chain on AH66F cells from the NA-382-treated group was also partially decreased, while that from the H-89-treated group was not changed. It was confirmed in vitro that after treatment with these protein kinase inhibitors for 48 h the expression of LFA-1 β-chain in the cells was decreased by NA-382, but not by H-89. These results suggested that the PKC inhibitor prolongs the life span of AH66F-bearing rats through inhibition of LFA-1-dependent adhesion of the cells.
  • Junko FUJII, Akimasa HIGASHI, Masahiro NAKANO
    1996 年 19 巻 12 号 p. 1614-1617
    発行日: 1996/12/15
    公開日: 2008/04/10
    ジャーナル フリー
    For analyzing the concentrations of drugs in hairs, a new method of digestion of hairs with Biopurase[○!R], a protease obtained from Bacillus subtilis, was examined. The concentrations of drugs in hairs were then determined in order to examine the usefulness of the protease for the digestion of hairs.The stability of five anticonvulsants in the protease solution was maintained over a 12-h period. In the clinical tests, the concentrations of the drugs in hairs obtained from patients who were taking anticonvulsants for a long time were determined. The concentration of phenobarbital in hairs in 10 patients taking phenobarbital ranged from 194 to 5020 ng/10 mg with a mean of 578 ng/10 mg, and the concentration of phenytoin in hairs in 6 patients taking phenytoin ranged from 44 to 299 ng/10 mg with a mean of 115 ng/10 mg. From these results, the transfer of phenobarbital and phenytoin from circulating blood into hairs was confirmed, and the usefulness of Biopurase[○!R] for the digestion of hairs was proved.
  • Tomomi UCHIYAMA, Akira YAMAMOTO, Harumi HATANO, Takuya FUJITA, Shozo M ...
    1996 年 19 巻 12 号 p. 1618-1621
    発行日: 1996/12/15
    公開日: 2008/04/10
    ジャーナル フリー
    The effectiveness and local toxicity of absorption enhancers on the absorption of phenol red (PR) from the large intestine of rats were examined using an in situ loop method. The absorption enhancers used in this study were sodium glycocholate (GC-Na), sodium taurocholate (TC-Na), sodium deoxycholate (DC-Na), EDTA, sodium salicylate (Sal-Na), sodium caprate (Cap-Na), diethyl maleate (DM), N-lauryl-β-D-maltopyranoside (LM) and mixed micelles (MM), all used at a concentration of 20 mM. Local toxicity was also investigated by assessing protein and phospholipid release as biological markers.DC-Na and MM were the most effective absorption enhancers, but they caused considerable release of proteins and phospholipids. GC-Na, TC-Na and LM, which caused little or only slight membrane damage, promoted PR absorption. Sal-Na, DM and EDTA did not enhance PR absorption. Overall, a correlation exists between the area under the curve of PR and protein and phospholipid release in the presence of absorption enhancers. However, GC-Na, TC-Na and LM promoted the absorption of PR with low toxicity. From these results, we concluded that GC-Na, TC-Na and LM are effective absorption enhancers which have low levels of toxicity at a concentration of 20 mM.
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