Protein Drug Oral Delivery: The Recent Progress

Lee, Hye-J. The Pharmaceutical Society of Korea 2002 Archives of Pharmacal Research Vol.25 No.5

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.

Current trends in benzodiazepine research

Klinger, M. The Pharmaceutical Society of Korea 1982 Archives of Pharmacal Research Vol.5 No.1

Thank you for inviting me as a guest speaker to this 30th anniversary of the Pharmaceutical Society of Korea. I take it as a compliment to may firm F. Hoffmann-La Roche and Co., Which, has not only dicovered and introduced the benzodiazepines, but has since then been continually in the fore-front of this research. As may subject is going to be "Current Trends in Benzodiazepine Research" I will try to have a look into pending problems. The history of the benzodiazepines has been told several times (e. g. Sternbach, Haefely).

Inhibitory Phlorotannins from the Edible Brown Alga Ecklonia stolonifera on Total Reactive Oxygen Species (ROS) Generation

Kang, Hye-Sook,Chung, Hae-Young,Kim, Ji-Young,Son, Byeng-Wha,Jung, Hyun-Ah,Choi, Jae-Sue The Pharmaceutical Society of Korea 2004 Archives of Pharmacal Research Vol.27 No.2

Reactive oxygen species (ROS) play an important role in the pathogenesis of many human degenerative diseases such as cancer, aging, arteriosclerosis, and rheumatism. Much attention has been focused on the development of safe and effective antioxidants. To discover sources of antioxidative activity in marine algae, extracts from 17 kinds of seaweed were screened for their inhibitory effect on total ROS generation in kidney homogenate using 2',7'-dichlorofluorescein diacetate (DCFH-DA). ROS inhibition was seen in three species: UIva pertusa, Symphyocladia latiuscula, and Ecklonia stolonifera. At a final concentration of 25 $\mu\textrm{g}$/mL, U. pertusa inhibited 85.65$\pm$20.28% of total ROS generation, S. latiscula caused 50.63$\pm$0.09% inhibitory, and the Ecklonia species was 44.30$\pm$7.33% inhibition. E. stolonifera OKAMURA (Lam-inariaceae), which belongs to the brown algae, has been further investigated because it is commonly used as a foodstuff in Korea. Five compounds, phloroglucinol (1), eckstolonol (2), eckol (3), phlorofucofuroeckol A (4), and dieckol (5), isolated from the ethyl acetate soluble fraction of the methanolic extrclct of E. stolonifera inhibited total ROS generation.

Anti-diabetic Agents from Medicinal Plants Inhibitory Activity of Schizonepeta tenuifolia Spikes on the Diabetogenesis by Streptozotocin in Mice

Kim, Chang-Jong,Lim, Jung-Sik,Cho, Seung-Kil The Pharmaceutical Society of Korea 1996 Archives of Pharmacal Research Vol.19 No.6

The Schizonepeta tenuifolia spikes (STS) have been used as a traditional folk medicine for antiinflammatory, analgesic, anti-pyretic and anti-spasmodic purpose in Korea. Phytosterols (mixture of campesterol 3.68%, stigmasterol 2.30% and ${\beta}$-sitosterol 94.02%) and hesperidin were isolated by chromatography from ether and n-BuOH fractions of STS respectively. These compounds significantly reduced the blood glucose level and lessened the loss of body weight and water consumption dose-dependently when administered at a i.p. doses of 10 and 20 mg/kg for 4 days after the i.v. injection of streptozotocin (I 80 mg/kg). In the morphologic study, these compounds showed protective activity on the pancreatic islets, especially .betha.-cells, from the degenerative changes by streptozotocin.

Extraction and Determination of Phytosterols from Corn Oil Foots

Kim, Sang-Ho,Park, Sang-Hoo,Ahn, Byung-Goo,Yi, Jeong-Sang,Park, Moo-Sin,Lee, Byeong-Ryong,Kim, Kweon The Pharmaceutical Society of Korea 1990 Archives of Pharmacal Research Vol.13 No.3

By saponification and extraction of corn oil foots abandoned as waste during oil refining, a mixture of phytosterols was obtained, and its major components were determined as .betha.-sitosterol, campesterol and stigmasterol by gas chromatographic analysis. The mixture is very cheap and regarded as an excellent substrate for direct fermentation of C-17 keto steroid intermediate for various steroid pharmaceuticals.

Effects of Nelumbinis Semen on Contractile Dysfunction in Ischemic and Reperfused Rat Heart

Kim, Jong-Hoon,Kang, Moon-Kyu,Cho, Chong-Woon,Chung, Hwan-Suck,Kang, Chang-Woon,Parvez, Shoukat,Bae, Hyun-Su The Pharmaceutical Society of Korea 2006 Archives of Pharmacal Research Vol.29 No.9

Nelumbinis Semen (NS), or lotus seed, is one of the most well-known traditional herbal medicines and is frequently used to treat cardiovascular symptoms in Korea. The anti-ischemic effects of NS on ischemia-induced isolated rat heart were investigated through analyses of changes in blood pressure, aortic flow, coronary flow, and cardiac output. The subjects in this study were divided into two groups: a control, untreated ischemia-induced group, and an ischemia-induced group treated with NS. There were no significant differences in perfusion pressure, aortic flow, coronary flow and cardiac output between the groups before ischemia was induced. The supply of oxygen and buffer was stopped for ten minutes to induce ischemia in isolated rat hearts, and NS was administered during ischemia induction. NS treatment significantly prevented decreases in perfusion pressure, aortic flow, coronary flow and cardiac output under ischemic conditions (p<0.01). In addition, the mechanism of the anti-ischemic effects of NS was also examined through quantitation of intracellular calcium content in rat neonatal cardiomyocytes. NS significantly prevented intracellular calcium increases induced by isoproterenol (p<0.01). These results suggest that NS has distinct anti-ischemic effects through calcium antagonism.

Synthesis of Praziquantel Derivatives and Their In Vitro Activity Against Adult Clonorchis sinensis

Kim, Choong-Sup,Min, Duk-Young The Pharmaceutical Society of Korea 1998 Archives of Pharmacal Research Vol.21 No.6

Several praziquantel derivatives have been prepared by the acylation of compound 5, and examined on their biological activity in vitro agninst adult clonorchis sinensis collected from rabbits infected with metacercariae which was isolated from Pseudorasbora parva, a second intermediate host, captured in Nakdong river in Korea.

Prevalence and Characterization of Vancomycin-Resistant Enterococci in Chicken Intestinles and Humans of Korea

Seong, Chi-Nam,Shim, Eun-Sook,Kim, Shin-Moo,Yoo, Jin-Cheol The Pharmaceutical Society of Korea 2004 Archives of Pharmacal Research Vol.27 No.2

The prevalence, genotype for antibiotic resistance and antibiotic susceptibility of vancomycin resistant enterococci (VRE) were determined. And molecular typings of the Enterococcus faecium isolates were analyzed. Prevalence of VRE in chickens, healthy children and intensive care unit (ICU) patients was 41.6%,7.9%, and 20.4%, respectively. Forty out of 54 isolates from chicken intestines, and 9 out of 11 from ICU patients were identified as Enterococcus faecium. Eleven out of 13 isolates from non-hospitalized young children were E. gallinarium. Twelve strains of E. faecalis were isolated from chicken intestines. The gene for the antibiotic resistance in E. faecium, and E. faecalis was vanA, while that in E. gallinarium was vanC1. E. faecium isolates were resistant to most of antibiotics except ampicillin and gentamicin. Molecular typing of the E. faecium strains obtained by pulse field gel electrophoresis and repetitive sequence-based PCR suggest that VRE transmit horizontally from poultry to humans, especially young children, via the food chains in Korea.

A Further Survey of the Action of Some Medicinal Plants on Drug Metabolism

Woo, Won-Sick,Shin, Kuk-Hyun The Pharmaceutical Society of Korea 1979 Archives of Pharmacal Research Vol.2 No.2

Tabulated results are presented of a test for an activity affecting on drug metabolism of 75 plant samples frequently used in the traditional medicine in Korea.

A Macrolide-Lincosamide-Streptogramin B Resistance Determinant Gene (ermJ) Cloned from B, anthracis 590

Kim, Hee-Sun,Choi, Eung-Chil,Kim, Byong-Kak,Park, Young-In The Pharmaceutical Society of Korea 1992 Archives of Pharmacal Research Vol.15 No.1

Bacillus anthracis 590 having an inducibla resistance determinant to MLS antibiotics was isolated from a soli sample in Korea. The resistance gene (ernJ) was cloned by Southern blotting of chromosomal DNA fragment digested by various restriction enzymes and coloy hybridization method and the cloned plasmid was named as pBA423. The size of inserted DNA fragment of pBS42 vector was about 2.9 kb and the DNA sequence of the subcloned fragment (Hinc II-Hinc II, 1.4kb) WAS determined. The DNA sequence of ernJ was composed of 357 bp for leader region and 861 bp for the structural gene. Because the leader sequence of ernJ was homologous to that of ermK, the expression of ernJ is also thought to be controlled by a transcriptionl attenuation mechanism.