• Journal of Pharmaceutical Investigation
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• v.18 no.3
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• pp.139-144
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• 1988

Piperacillin phthalidyl ester was synthesized by reacting piperacillin with triethylamine and bromophthalide in acetone and its chemical structure was determined by UV, IR, and PMR. The partition coefficient of the ester was increased and the ester was more lipophilic and less water soluble than piperacillin. The ester did not show the antimicrobial activity against Bacillus subtilis ATCC 6633 in vitro, but when hydrolyzed, the parent drug of ester, piperacillin, revealed antimicrobial activity in vivo. After a single oral dose of both piperacillin and the ester to rabbits, the serum piperacillin concentration was measured by bioassay. The ester exhibited improved pharmatokinetic characteristics: $T_{max}\;of\;2hr,\;C_{max}\;of\;4.26{\mu}g{\cdot}ml^{-1},K_{el}\;of\;0.057hr^{-1},\;and\;total\;AUC\;of\;85.42{\mu}g{\cdot}hr{\cdot}ml^{-1}$. Piperacillin on the other hand, did not exhibit any gastro-intestinal absorption.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.572-584
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• 2002

Rapid development in molecular biology and recent advancement in recombinant technology increase identification and commercialization of potential protein drugs. Traditional forms of administrations for the peptide and protein drugs often rely on their parenteral injection, since the bioavailability of these therapeutic agents is poor when administered nonparenterally. Tremendous efforts by numerous investigators in the world have been put to improve protein formulations and as a result, a few successful formulations have been developed including sustained-release human growth hormone. For a promising protein delivery technology, efficacy and safety are the first requirement to meet. However, these systems still require periodic injection and increase the incidence of patient compliance. The development of an oral dosage form that improves the absorption of peptide and especially protein drugs is the most desirable formulation but one of the greatest challenges in the pharmaceutical field. The major barriers to developing oral formulations for peptides and proteins are metabolic enzymes and impermeable mucosal tissues in the intestine. Furthermore, chemical and conformational instability of protein drugs is not a small issue in protein pharmaceuticals. Conventional pharmaceutical approaches to address these barriers, which have been successful with traditional organic drug molecules, have not been effective for peptide and protein formulations. It is likely that effective oral formulations for peptides and proteins will remain highly compound specific. A number of innovative oral drug delivery approaches have been recently developed, including the drug entrapment within small vesicles or their passage through the intestinal paracellular pathway. This review provides a summary of the novel approaches currently in progress in the protein oral delivery followed by factors affecting protein oral absorption.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.10
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• pp.1386-1398
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• 2010

Soybean contains a high concentration of carbohydrates that consist mainly of non-starch polysaccharides (NSP) and oligosaccharides. The NSP can be divided into insoluble NSP (mainly cellulose) and soluble NSP (composed mainly of pectic polymers, which are partially soluble in water). Monogastric animals do not have the enzymes to hydrolyze these carbohydrates, and thus their digestion occurs by means of bacterial fermentation. The fermentation of soybean carbohydrates produces short chain fatty acids that can be used as an energy source by animals. The utilization efficiency of the carbohydrates is related to the chemical structure, the level of inclusion in the diet, species and age of the animal. In poultry, soluble NSP can increase digesta viscosity, reduce the digestibility of nutrients and depress growth performance. In growing pigs, these effects, in particular the effect on gut viscosity, are often not so obvious. However, in weaning piglets, it is reported that soy oligosaccharides and soluble NSP can cause detrimental effects on intestinal health. In monogastrics, consideration must be given to the anti-nutritive effect of the NSP on nutrient digestion and absorption on one hand, as well as the potential benefits or detriments of intestinal fermentation products to the host. This mirrors the needs for i) increasing efficiency of utilization of fibrous materials in monogastrics, and ii) the maintenance and improvement of animal health in antibiotic-free production systems, on the other hand. For example, ethanol/water extraction removes the low molecular weight carbohydrate fractions, such as the oligosaccharides and part of the soluble pectins, leaving behind the insoluble fraction of the NSP, which is devoid of anti-nutritive activities. The resultant product is a high quality soy protein concentrate. This paper presents the composition and chemical structures of carbohydrates present in soybeans and discusses their nutritive and anti-nutritive effects on digestion and absorption of nutrients in pigs and poultry.

• Journal of Nutrition and Health
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• v.34 no.2
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• pp.141-149
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• 2001

This study done to investigate the hypocholesterolemic effect of ow dietary fiber in a high cholesterol diet in aspect of cholesterol absorption and excretion using Sprague Dawley rats. After feeding diets containing 0.5% cholesterol and 5% tangerine pulp, sea tangle or prickly pear cactus for four weeks, we measured the levels of plasma and liver cholesterol and triglyceride, fecal neutral sterols and fecal radioactivity after ingestion 14(sup)C-cholesterol. We also examined platelet aggregation and histological change in liver tissues in association of hypercholesterolemia. The liver to body weight ratio was significantly(p<0.01) lower in rats fed prickly pear cactus than in other groups. The levels of plasma total cholesterol, LDL-cholesterol and triglyceride were decreased significantly(p<0.01) in the prickly pear cactus group compared with the control, while there was no difference in the liver levels of total cholesterol and triglyceride among groups. Fecal corprostanol and cholesterol were significantly(p<0.01) higher groups of control and prickly pear cactus compared to the other two groups. Radioisotope excretion after ingestion of 14(sup)C-cholesterol was higher in the control group than in tangerine pulp group or sea tangle group, with the highest in prickly pear group. Radioisotope excretion was the highest during the 2nd and 3rd days in all groups. Hematocrit and platelet aggregation were decreased in all fiber groups compared to the control, but not statistically different. Microscopic examination showed that cholesterol diet cause a fat accumulation in the liver and prickly pear cactus decreased the fat accumulation. Result indicates that prickly pear cactus has hypocholesterolemic effect by decreasing absorption and increasing excretion of cholesterol, thereby protective effect on fatty liver. Control group fed diet containing high cholesterol and low fiber seems to have a self control system in cholesterol absorption and excretion preventing hypercholesterolemia. (Korean J Nutrition 34(2) : 141-149, 2001)

• Bulletin of the Korean Chemical Society
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• v.35 no.11
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• pp.3188-3194
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• 2014

Compound K (CK) was formulated as polymeric micelles (PM) using Pluronic$^{(R)}$ F-127 to enhance the oral absorption of CK, an intestinal bacterial metabolite of ginseng protopanaxadiol saponin. The physicochemical properties of Ck-loaded PM were characterized and an in vitro transport study using the Caco-2 cell system as well as an in vivo pharmacokinetic study using SD rats was carried out. The hydrodynamic mean particle size of CK-loaded PM (CK-PM) was $254{\pm}23.45nm$ after rehydration and the drug loading efficiency was ca. 99.9%. The FT-IR spectroscopy, X-ray diffraction, differential scanning calorimetry and scanning electron microscopy data supported the presence of a new solid phase in the PM. The $P_{app}$ value of in vitro Caco-2 cell permeation of CK-PM and the oral absorption of CK was enhanced about 1.2-fold and 2.6-fold compared to CK suspension, respectively, showing that the present PM formulation enabled an enhancement of oral CK absorption.

• Korean Journal of Clinical Pharmacy
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• v.16 no.1
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• pp.57-62
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• 2006

The purpose of this study was to investigate the effect of naringenin, one of flavonoids, on the pharmacokinetics and bioavailability of diltiazem (15 mg/kg) after oral administration of diltiazem with or without naringenin (2.0, 10 and 20 mg/kg) in rabbits. Coadministration of naringenin increased the absorption rate constant $(K_a)$, the area under the plasma concentration-time curve (AUC) and peak concentration $(C_{max})$ of diltiazem compared to the control group, but only significantly (p<0.05) by 10mg/kg of naringenin coadministration. The absolute bioavailability (AB%) of diltiazem by coadministration ranges from 7.8% to 10.3%, increased more than control (7.2%), and relative bioavailability (RB%) of diltiazem is increased from 1.08- to 1.43-fold. Coadministration caused on significant changes in the terminal half-lives $(t_{1/2})$ and the time to reach the peak concentration $(T_{max})$ of diltiazem. On the other hand, coadministration of naringenin increased the AUC desacetyldiltiazem, significantly at the dose of 10mg/kg. But the metabolite ratio (MR) was decreased, significantly at 10mg/kg of naringenin. Based on these results, we can make a conclusion that the increased bioavailability and the significant changes of these pharmacokinetic parameters might be due to naringenin, which possess the potency to inhibit the metabolizing enzyme (CYP3A4) in the liver and intestinal mucosa, and also inhibit the P-glycoprotein efflux pump in the intestinal mucosa.

• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.185-192
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• 1995

Precipitation reaction occured between berberine in Coptidis Rhizoma and glycyrrhizin in Glycyrrhizae Radix when they were boiled together in aqueous solution and the supernatant solution thus obtained did not show any antibacterial activity which was derived from berberine. The content of berberine in BG and CGP by HPLC analysis were 41.1%, 8.3% respectively. BG was occured mostly at pH 5.0. The solubility of berberine was 0.15%, while that of BG and CGP was 0.07%, 0.12%, respectively. CGP shown more increased antibacterial activity to gram positive bacteria, S. dysenteriae and K. pneumoniae than berberine. The absorption rates of CGP in stomach, duodenum and jejunum of rats were compared with those of Coptidis Rhizoma water extracts (CR), which were increased more than CR. The time required for the maximum serum concentration of berberine from CGP in mice was 90 minutes after oral administration. The maximum serum concentration of berberine from CGP was higher than that from CR. The dissolution of CGP was increased more than berberine and BG in both artificial gastric and intestinal fluids. The dissolution of CGP pill made from gelatin was 63.4% in artificial gastric fluids and that made from CMC was 76.0% in artificial intestinal fluids.

• Mass Spectrometry Letters
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• v.8 no.2
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• pp.34-38
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• 2017

The purpose of this study was to develop a cocktail approach for the measurement of the permeability of marker compounds, caffeine and propranolol (high permeability), ofloxacin (intermediate), atenolol (low), and quinidine (P-glycoprotein substrate), simultaneously. Then we compared the permeability in Caco-2 cells with that in rat intestinal segments. The difference between individual measurement and cocktail approach was less than 20 %, and the permeabilities of these compounds were similar to those previously reported, suggesting that the cocktail transport study and simultaneous drug analysis were successfully developed and validated in this study. Additionally, in the application of this cocktail method, the permeability of five drugs in rat jejunum was similar to that in ileum but different from that in colon, which was measured using the Ussing chamber system. Moreover, permeability in jejunum and ileum was similar to that in Caco-2 cells. In conclusion, the permeability in Caco-2 cells was equivalent to the permeability in rat jejunum and ileum determined with the Ussing system. Therefore, this newly developed cocktail assay and its application to the Ussing system can be a useful tool for robust and rapid screening for site-specific permeability in rat intestine, thus accelerating the prediction of absorption of new chemical entities.

• Biomolecules & Therapeutics
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• v.29 no.4
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• pp.353-364
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• 2021

The gastrointestinal (GI) tract is a series of hollow organs that is responsible for the digestion and absorption of ingested foods and the excretion of waste. Any changes in the GI tract can lead to GI disorders. GI disorders are highly prevalent in the population and account for substantial morbidity, mortality, and healthcare utilization. GI disorders can be functional, or organic with structural changes. Functional GI disorders include functional dyspepsia and irritable bowel syndrome. Organic GI disorders include inflammation of the GI tract due to chronic infection, drugs, trauma, and other causes. Recent studies have highlighted a new explanatory mechanism for GI disorders. It has been suggested that autophagy, an intracellular homeostatic mechanism, also plays an important role in the pathogenesis of GI disorders. Autophagy has three primary forms: macroautophagy, microautophagy, and chaperone-mediated autophagy. It may affect intestinal homeostasis, host defense against intestinal pathogens, regulation of the gut microbiota, and innate and adaptive immunity. Drugs targeting autophagy could, therefore, have therapeutic potential for treating GI disorders. In this review, we provide an overview of current understanding regarding the evidence for autophagy in GI diseases and updates on potential treatments, including drugs and complementary and alternative medicines.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.2
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• pp.221-228
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• 2017

Objective: The objective of this experiment was to characterize the mRNA expression profile of type IIb sodium-inorganic phosphate cotransporter (NaPi-IIb) and the biochemical values of serum alkaline phosphatase (AKP), calcium, inorganic phosphorus, tibial ash and minerals of broiler chickens with aging. Methods: A total of 56 one-day-old Arbor Acres male broiler chickens were used. Broiler chickens were weighed and samples were collected weekly from day 1. Results: The result showed that before the growth inflection point, ash, calcium, and phosphorus content in the tibia of broiler chickens increased with growth (before 3 weeks of age), although there were no significant differences in chicks at different ages in the later period of the experiment and weight gain rate was relatively slow at this stage (4 to 6 weeks). NaPi-IIb gene expression in the small intestine in the early growth stage was higher than that in the later growth stage. Expression of calbindin and the vitamin D receptor protein in the intestinal mucosa increased with age in the duodenum and jejunum. Serum AKP activity first increased and subsequently decreased after peaking at 1 week of age, but there was no significant difference after 3 weeks of age. Conclusion: These results show that compared with the early growth stage, the weight-gain rate of broiler chickens in the late growth stage gradually decreased with gradual tibia maturation, along with weaker positive transport of phosphorus in the intestine and reinforced re-absorption of phosphorus in the kidney, which might be the reason that phosphorus requirement in the late growth stage was decreased.