• Journal of Pharmaceutical Investigation
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• 제9권1호
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• pp.15-19
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• 1979

The absorption rate of lysino-methylene-ampicillin from the rat small intestine, compared with ampicillin, was determined in vitro and in situ to establish the biopharmaceutical properties of lysino-methylene-ampicillin which is one of the new penicillinase-resistance antibiotics. The half of administered dose was absorbed rapidly within thirty minutes. The water-oil distribution coefficient of lysino-methylene-ampicillin was 0.03 in chloroform versus buffer system with $Na_{2}HPO_{4}-citric$ acid of pH5.2 at $37^{\circ}C$, and its dissolution rate reached the plateau in an hour and then represented 0.6 percent of equilibrium solubility

• Journal of Pharmaceutical Investigation
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• 제12권4호
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• pp.112-125
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• 1982

Sulfamethoxazole particles were microencapsulated using the gelatin-acacia complex coacervation method. Micromeritic properties and dissolution characteristics of the microcapsules were studied. The particle size distribution followed log-normal form. As the hardening time increased, the particle size and wall thickness increased ($45.3-52.0\;{\mu}m$, $2.02-5.12\;{\mu}m$, respectively). This is considered to be due to the cross-linked wall structure of formalized microcapsules which prevents shrinking of gelatin during the dehydration and drying processes. An increase of hardening time clearly delayed the release rate. The in vitro 50% dissolution time $(t_{50})$ for unencapsulated sulfamethoxazole powder was less than 3 min.; for microcapsules hardened for 30 min, the $t_{50}$ was 20.1 min.; for those hardened for 60 min. the $t_{50}$ was 25.0 min.; for those hardened for 120 min., the $t_{50}$ was 35.8 min. The surface of the unhardened microcapsules was smooth and had no cracking or pore penetration. However, the surface of the hardened microcapsules was folded and invaginated.

• Journal of Pharmaceutical Investigation
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• 제40권4호
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• pp.201-212
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• 2010

Self-organized nanogels from polysaccharide derivatives offer a promising approach in treatment of cancer due to their flexibility in chemistry and their ability to improve the therapeutic index of a drug by modifying biodistribution by their preferential localization at target sites and lower distribution in normal healthy tissues. These properties have promoted studies of active cancer targeting by self-organized nanogels for even better accumulation in solid tumors. However although many researchers have reported their potential by using cell culture systems and small animal tumor models in cancer therapy, these nanogels need more decoration such as conjugation with targeting moiety and endowment of stimuli-sensitivity for precise targeting of the cancer site. In this review, we summarize the recent efforts in developing novel targeting approaches via active endocytosis and stimuli-sensitive systems responding to hyperthermic or acidic tumor pH conditions.

• Journal of Pharmaceutical Investigation
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• 제24권3호
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• pp.167-176
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• 1994

The microcapsules of amoxicillin using stearyl alcohol and polyethyleneglycol 8000 (PEG 8000) were prepared by a emulsion melted-cooled process in water phase. The size distribution, dissolution test, observation with SEM and in vivo test were investigated. The microcapsules obtained were spherical, uniform and free flowing particles. The release of drug from microcapsule was increased in proportional to the content of PEG 8000. As the PEG 8000 content increased, the particle size of microcapsule was decreased. Sanning electron micrograph study revealed that microcapsules had comparatively rough surfaces as drug content was increased. The $AUC_{0-12}$ after administration of amoxicillin microcapsules was more increased 40% as compared with the AUC after administration of amoxicillin powder in rabbits.

• Journal of Pharmaceutical Investigation
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• 제18권1호
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• pp.9-13
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• 1988

Physicochemical properties of oil in water microemulsions containing soybean oil and egg phosphatide were observed for 3 weeks under the storage condition of $4^{\circ}C$ refrigerator. Changes in major fatty acid content, particle size distribution, rheogram, acid value and pH value were measured by gas chromatograph, laser particle sizer, Coulter counter and rheometer. From above experiments following conclusions were obtained; 1) Mean particle diameter was shifted from 240 to 266mm. 2) No significant changes were observed in the content of major fatty acids of soybean oil, rheogram, acid value and pH value.

• Journal of Pharmaceutical Investigation
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• 제21권4호
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• pp.253-262
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• 1991

Microencapsulation of sodium ascorbate with cellulose acetate phthalate(CAP) by coacervation/ phase separation method were carried out. Various factors affecting microencapsulation, i.e., surfactant concentration. CAP concentration, stirring speed and treatment of spermaceti as a sealing agent were studied. Dissolution rate. particle size distribution, surface feature and stability test were investigated. CAP microcapsules prepared using 0.5% span 80 as a surfactant showed smooth and round surfaces. The release of sodium ascorbate was retarded by microencapsulation with CAP and by sealant treatment with spermaceti. When triturated with sodium bicarbonate, CAP microcapsules were more stable than unencapsulated sodium ascorbate under various RH conditions at $37^{\circ}C$.

• Journal of Pharmaceutical Investigation
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• 제19권4호
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• pp.195-202
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• 1989

In attempt to improve the chemotherapeutic activity of adriamycin, adriamycin-entrapped HSA microspheres were prepared and investigated by the various in vitro experiments. The shape, surface characteristics and size distribution of HSA microspheres are observed by scanning electron microscopy. The in vitro drug release, albumin matrix degradation by protease of HSA microspheres were studied. The shape of HSA microspheres were spherical and the surface was smooth and compact. The size of HSA microspheres ranged from 0.4 to $2.5\;{\mu}m$ and have average diameters of 0.5 to $0.7\;{\mu}m$. The size distribution of HSA microspheres prepared by ultrasonication was mainly affected by albumin concentration and heating time in the process of hardening. In in vitro, almost all adriamycin was released from HSA microspheres for 8 hr. Analysis of the resulting adriamycin release profiles demonstrated that adriamycin is released from the microspheres in two distinct steps, a fast phase (until 30 min) followed by a much slower sustained release phase. Drug release, which is due to diffusion, was depended on the rate of matrix hydration. Drug release was largely affected by albumin concentration and heating temperature during the process of hardening. Albumin matrix degradation of HSA microspheres was affected by heating temperature and albumin concentration. Higher temperature and longer times generally produce harder, less porous, and slowly degradable microspheres.

• Journal of Pharmaceutical Investigation
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• 제33권4호
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• pp.287-292
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• 2003

A novel antitumor agent, antibody-endostatin fusion protein $(anti-HER2/neu\;IgG3C_H3-Endostatin,\;AEFP)$ formed by genetic engineering procedure from antibody (Ab) which specifically targets to tumor cells ad angiogenesis inhibitor, endostatin (Endo) that has excellent antitumor effect, minimizes the toxicity of normal cells and selectively kills only tumor cells. The purpose of this study is to evaluate the phamacokinetic parameters and to analyze the localization of AEFP. After an intravenous injection of $150\;{\mu}l\;(5\;{\mu}Ci)\;[^{125}I]Ab,\;[^{125}I]AEFP$ to mice, blood was collected though retroorbital plexus from 15 min to 2880 min. Following the jugular vein injetion of $150\;{\mu}l\;(10\;{\mu}Ci)\;[^{125}I]Endo$, blood was collected by the use of carotid artery cannulation from 0.25 min to 30 min. Consequently, Endo was very rapidly removed from plasma compartment within 30 min. On the other hand, AEFP similar to Ab was slowly cleared from plasma. Also, Endo was metabolized about 40% within 30 min. However, AEFP was shown to metabolize less than 10% within 2880 min. The organ distribution of Endo was in order kidney, lung, spleen. Both Ab and AEFP were localized in order spleen, kidney, liver. Futhermore the tumor/blood distribution ratio of AEFP at 96 hours after injection is about 20 times higher than it of Endo at one hour after injection. In conclusion, these studies demonstrate that the anti-cancer or suppression of angiogenesis effect of Endo may be improved by the use of AEFP because the longer half life and stability of AEFP is able to selectively target antigens expressed on tumors.

• The Korean Journal of Physiology and Pharmacology
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• 제28권2호
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• pp.153-164
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• 2024

This study aimed to identify metabolic biomarkers and investigate changes in intestinal microbiota in the feces of healthy participants following administration of Lactococcus lactis GEN-001. GEN-001 is a single-strain L. lactis strain isolated from the gut of a healthy human volunteer. The study was conducted as a parallel, randomized, phase 1, open design trial. Twenty healthy Korean males were divided into five groups according to the GEN-001 dosage and dietary control. Groups A, B, C, and D1 received 1, 3, 6, and 9 GEN-001 capsules (1 × 10¹¹ colony forming units), respectively, without dietary adjustment, whereas group D2 received 9 GEN-001 capsules with dietary adjustment. All groups received a single dose. Fecal samples were collected 2 days before GEN-001 administration to 7 days after for untargeted metabolomics and gut microbial metagenomic analyses; blood samples were collected simultaneously for immunogenicity analysis. Levels of phenylalanine, tyrosine, cholic acid, deoxycholic acid, and tryptophan were significantly increased at 5-6 days after GEN-001 administration when compared with predose levels. Compared with predose, the relative abundance (%) of Parabacteroides and Alistipes significantly decreased, whereas that of Lactobacillus and Lactococcus increased; Lactobacillus and tryptophan levels were negatively correlated. A single administration of GEN-001 shifted the gut microbiota in healthy volunteers to a more balanced state as evidenced by an increased abundance of beneficial bacteria, including Lactobacillus, and higher levels of the metabolites that have immunogenic properties.

• 한국임상약학회지
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• 제28권3호
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• pp.230-237
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• 2018

Objective: To compare adverse event reporting patterns between ethical-the-counter and over-the-counter drugs from community pharmacies and outpatient settings. Methods: We conducted a descriptive study using the adverse event reporting database, wherein data were collected from the regional pharmacovigilance centers of the Korean Pharmaceutical Association between January 1, 2016 and December 31, 2016. The reported drugs were classified into either ethical-the-counter or over-the-counter drugs, and we compared the distribution of patient age and gender, frequent adverse events and medications, serious adverse events, and causality assessment results, where causality assessments were performed according to the World Health Organization-The Uppsala Monitoring Centre's system. Results: We included 17,570 reports (75,451 drug-adverse event pairs). Ethical-the-counter and over-the-counter drugs accounted for 81.4% and 18.6% of the total adverse event reports, respectively. The use of over-the-counter drugs was higher in females and patients aged <18 years, whereas the use of ethical-the-counter drugs was higher in those aged >65 years. Alimentary tract and metabolism drugs, and respiratory system drugs were the most frequent ethical-the-counter and over-the-counter drugs, respectively. From causality assessment results, "possible" (75.4%) was the most commonly assigned category for ethical-the-counter drugs, while "possible" (44.0%) and "unlikely" (47.7%) were the most common categories for over-the-counter drugs. The distribution of serious adverse events were similar for both ethical-the-counter and over-the-counter drugs. Conclusion: Differences were observed in age, gender, reported medications, and symptoms for both ethical-the-counter and over-the-counter drugs. Further pharmacovigilance activities considering the adverse event characteristics of over-the-counter drugs, which are comparable to ethical-the-counter drugs, should be performed.