• Journal of Pharmaceutical Investigation
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• v.39 no.2
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• pp.97-106
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• 2009

Although lovastatin (LS) is widely used in the treatment of hypercholesterolemia, its bioavailability is known to be around 5%. This study was aimed to increase the solubility and dissolution-permeation rates of LS using solid dispersions (SDs) with bile salts. The solubilities of LS in water, aqueous bile salt solutions and non-aqueous vehicles were determined, and effects of bile salts on the cellulose or duodenal permeation of LS from SDs were evaluated using a horizontal permeation system. SDs were prepared at various ratios of LS to carriers, such as sodium deoxycholate (SDC), sodium glycocholate (SGC) and/or 2-hydroxypropyl-$\beta$-cyclodextrin (HPCD). The addition of bile salts (25 mM) in water increased markedly the solubility of LS by the micellar solubilization. Some non-aqueous vehicles were effective in solubilizing LS. From differential scanning calorimetric studies, it was found that the crystallinity of LS in SDs disappeared, indicating a formation of amorphous state. The SDs showed markedly enhanced dissolution compared with those of their physical mixtures (PMs) and drug alone. In the dissolution-permeation studies using a cellulose membrane, the donor and receptor solutions were maintained as a sink condition using pH 7.0 phosphate buffer containing 0.05% sodium lauryl sulfate (SLS). The flux of LS alone was nearly same as that of LS-SDC-HPCD (1:3:6) PM. However, the flux of LS-SDC-HPCD (1:3:6) SD slightly increased compared with drug alone and PM, suggesting that entrapment of LS in micelles does not significantly hinder the permeation across cellulose membrane. In the dissolution-duodenal permeation studies using a LS-HPCD-SDC (1:3:6) SD, the addition of various bile salts in donor solutions (25 mM) enhanced the permeation of LS markedly, and the fluxes were found to be $0.69{\pm}0.41$, $0.87{\pm}0.51$, $0.84{\pm}0.46$, $0.47{\pm}0.17$ and $0.68{\pm}0.32{\mu}g/cm^2/hr$ for sodium cholate (SC), SDC, SGC, sodium taurodeoxycholate (STDC) and sodium taurocholate (STC), respectively. The stepwise increase of donor SGC concentration increased the flux dose-dependently. From the relationship of donor SGC concentration and flux, the concentration of SGC initiating the permeation across the duodenal mucosa was calculated to be 11.1 mM, which is nearly same as the critical micelle concentration (CMC, 11.6 mM) of SGC. However, with no addition of bile salts and below CMC, the permeation was very limited and irratic, indicating that LS itself is very poor permeable. Higher protions of bile salt in SD such as LS-SDC or LS-SGC (1 : 49 and 1 : 69) showed highly promoted fluxes. In conclusion, SD systems with bile salts, which may form their micelles in intestinal fluids, might be a promising means for providing enhanced dissolution and intestinal permeation of practically insoluble and non-absorbable LS.

• CELLMED
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• v.3 no.1
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• pp.9.1-9.10
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• 2013

In traditional systems of medicine including homeopathy, the Condurango extract (Con) is often used to cure stomach cancer mainly, without having any scientific validation of its anti-cancer ability. Con has therefore been tested against non-small-cell lung cancer cells (NSCLC) A549 and NCI-H522 (H522) known to contain the KRAS mutation, making them resistant to most chemotherapeutic agents. As cancer cells generally defy cytotoxicity developed by chemopreventive agents and escape cell death, any drug showing the capability of preferentially killing cancer cells through apoptosis is worth consideration for judicious application. A549 and H522 cells were exposed to $0.35{\mu}g/{\mu}l$ and $0.25{\mu}g/{\mu}l$ of Con, respectively, for 48 h and analysed based on various protocols associated with apoptosis and DNA damage, such as MTT assay to determine cell viability, LDH assay, DNA fragmentation assay, comet assay, and microscopical examinations of DNA binding fluorescence stains like DAPI, Hoechst 33258 and acridine orange/ethidium bromide to determine the extent of DNA damage made in drug-treated and untreated cells and the results compared. Changes in mitochondrial membrane potential and the generation of reactive oxygen species were also documented through standard techniques. Con killed almost 50% of the cancer cells but spared normal cells significantly. Fluorescence studies revealed increased DNA nick formation and depolarized membrane potentials after drug treatment in both cell types. Caspase-3 expression levels confirmed the apoptosis-inducing potential of Con in both the NSCLC lines. Thus, overall results suggest considerable anticancer potential of Con against NSCLC in vitro, validating its use against lung cancer by practitioners of traditional medicine including homeopathy.

• Journal of Applied Biological Chemistry
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• v.65 no.2
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• pp.113-120
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• 2022

We examined the anti-inflammatory properties of Nostoc commune HCW0811 in lipopolysaccharide-stimulated RAW264.7 macrophage cells. The anti-inflammatory activity of HCW0811 on viability of treated cells was assessed by measuring the level of expression of NO, prostaglandin E₂ and pro-inflammatory cytokines, namely interleukin-1β, interleukin-6, and tumor necrosis factor-α in HCW0811 treated RAW 264.7 macrophages. HCW0811 was non-toxic to cells and inhibited the production of cytokines in a concentration-dependent manner. In addition its treatment suppressed the production of pro-inflammatory cytokines in a dose-dependent manner, and concomitantly decreased the protein expressions of inducible NO synthase and cyclooxygenase-2. Moreover, the levels of the phosphorylation of mitogen-activated protein kinase family proteins such as extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and nuclear factor kappa B were reduced by HCW0811. These findings suggest that the HCW0811 collected from Daejeon National Cemetery have anti-inflammatory effects, and demonstrated its efficacy in cell-based in vitro assays.

• The Korean Society of Law and Medicine
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• v.24 no.2
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• pp.119-145
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• 2023

The Pharmaceutical Affairs Act stipulates medication counseling as an obligatory requirement in the case of preparation of medicine. In fact, there are many cases where pharmacists only tell patients the dose and time and do not properly guide them on taking medications. However, in light of the current situation where non-face-to-face treatment is being attempted, there is a high possibility of drug-taking accidents due to insufficient medication guidance. In addition, as an aging society progresses, the need for explanations on pharmaceuticals is increasing. If a pharmacist causes damage to a patient by failing to give appropriate medication guidance, the patient can claim compensation for damages. In addition, if a drug accident occurs due to a conflict between the pharmacist's duty to guide medication and the doctor's duty to explain, a joint tort is established between the pharmacist and the doctor. Nevertheless, there are cases in which only doctors are judged to bear the tort liability. However, the Pharmaceutical Affairs Act includes providing information for the selection of over-the-counter drugs in the medication guidance as part of the medication guidance obligation. Therefore, in order to reconsider the importance of the medication-taking guidance duty, it is necessary to define the medicationaking information provision method and the medication-taking guidance duty as separate concepts. In addition, it is necessary to amend related regulations centered on patients so that medication guidance, such as side effects of medicines and interactions with concomitant medications, can be made in detail.

• YAKHAK HOEJI
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• v.58 no.4
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• pp.268-276
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• 2014

Background: World Health Organization considers opioid analgesic use as an important measure in the treatment of pain relief. However, there are limited data about the pattern of opioid analgesic use in tertiary care hospitals in Korea. The aim of this study was to describe the trends in the prescribed amount of the opioid for 13 years from 2000 to 2012 in a single tertiary care hospital. Methods: The data from the prescribed amount of opioid use in patients aged over 18 years were retrieved from medical charts and longitudinal pharmacy records of Seoul National University Hospital. Yearly prescribed amount of opioids were calculated using defined daily dose adjusted by hospital stay (DDD/1000${\bullet}$HS). Results: Over the 13 years of the study period, overall use of opioid has increased by 64.1%. Although, the opioid use by hospitalized patients comprised 98%~99% of total amount of opioid use, the proportions of opioid use by outpatient and by cancer patient increased from 1.1% to 2.2% and from 60.5% to 69.3%, respectively. The use of non-injectable opioids has increased by 47% and that of injectables has increased by 70%. While the amount of codeine and morphine use has decreased, the use of both transdermal and injection formulation of fentanyl has increased dramatically. Also, the use of oxycodone has increased, especially in outpatient setting. Conclusion: This longitudinal study showed that opioid analgesic use in tertiary hospital, especially in outpatient is continuously increasing. Improvement in pain management in tertiary care hospital can be cautiously inferred based on this results.

• YAKHAK HOEJI
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• v.36 no.5
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• pp.412-426
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• 1992

Effects of beta-carotene on the immunobiological responses were studied in ICR mice. ICR male mice were divided into 8 groups (10 mice/group), and beta-carotene at doses of 4, 20 and 100 mg/kg were orally administered to ICR mice once daily for 28 consecutive days. Cyclophosphamide (CY) was injected intraperitoneally (i.p.) to ICR mice with a single dose of 5 mg/kg body weight at 2 days before secondary immunization. Mice were sensitized and challenged with sheep red blood cells (5-RBC). Immune responses were evaluated by humoral immunity, cellular immunity and non-specific immunity. The results of this study were summarized as follows: (1) Beta-carotene significantly increased the weight ratios of liver, spleen and thymus to body weight depending on dose, and significantly increased the increasing rate of body weight and the number of circulating leukocyte. (2) Beta-carotene dose-dependently increased hemagglutination titer, Arthus reaction and hemolytic plaque forming cell related to humoral immunity. (3) Beta-carotene significantly increased delayed-type hypersensitivity reaction and rosette forming cell related to cellular immunity. (4) Beta-carotene dose-dependently increased phagocytic activity, and significantly increased natural killer (NK) cell activity. (5) Beta-carotene dose-dependently inhibited reductions in humoral immunity, cellular immunity, NK cell activity and phagocytic activity by treatment with CY.

• Journal of Pharmaceutical Investigation
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• v.34 no.6
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• pp.483-489
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• 2004

Fexofenadine HCl is non-sedating histamine H1 receptor antagonist that can be used for the treatment of seasonal allergic rhinitis. The objective of this study was to investigate whether the carriers of deformable liposomes can enhance the transepithelial permeability of fexofenadine HCl across the in vitro ALI human nasal monolayer model. Characterization of this model was achieved by bioelectric measurements and morphological studies. The passage 2 and 3 of cell monolayers exhibited the TEER value of $2852\;{\pm}\;482\;ohm\;{\times}\;cm^2$ on 11 days of seeding and maintained high TEER value for 5 days. The deformable liposome of fexofenadine HCl was prepared with phosphatidylcholine (PC) and cholic acid using extruder method. The mean particle size was about 200 nm and the maximum entrapment efficiency of 33.0% was obtained in the formulation of 1% PC and $100\;{\mu}g/ml$ fexofenadine HCl. The toxicity of the deformable liposome to human nasal monolayers was evaluated by MTT assay and TEER value change. MTT assay showed that it has no toxic effect on the nasal epithelial cells in 2-hour incubation when the PC concentration was below 1%. However, deformable liposome could not enhance the transepithelial permeability $(P_{app})$ and cellular uptake of fexofenadine HCl. In conclusion, the in vitro model could be used in nasal drug transport studies and evaluation of transepithelial permeability of formulations.

• The Journal of Korean Medicine
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• v.30 no.2
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• pp.88-103
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• 2009

Objectives: There is currently increased interest in the identification of natural antioxidant compounds derived from various plants. Peony Root (PR) is used worldwide for the treatment of many types of cardiovascular disease including atherosclerosis and hypertension. It has been used in Korean traditional medicine for the treatment of glycosuria, hypertension and cancer. However, to date, no studies concerning the antioxidant properties of PR have been conducted. Therefore, this study was conducted to evaluate the in vitro scavenging activity, inhibitory effect of LDL oxidation of pro-oxidant reactive species and anti-thrombosis effect in response to treatment with PR using various screening methods including biological and non-biological oxidants. Methods: In this study, the antioxidant activity of extract from PR was studied with in vitro methods by measuring the antioxidant activity by TEAC, measuring the scavenging effects on reactive oxygen species (ROS) [superoxide anion, hydroxyl radical] and on reactive nitrogen species (RNS) [nitric oxide and peroxynitrite] as well as measuring the inhibitory effect on $Cu^{2+}$-induced human LDL oxidation and the inhibitory effect on collagen-induced platelet aggregation. Results: The PR extracts were found to have a potent scavenging activity of oxidative stress [DPPH, superoxide anion, hydroxyl radical, nitric oxide and peroxynitrite, etc.] as well as an inhibitory effect on LDL oxidation and on platelet aggregation. Conclusions: The PR extracts have anti-oxidative and anti-atherosclerotic effects in vitro system, which can be used for developing pharmaceutical drugs against oxidative stress and atherosclerosis.

• CELLMED
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• v.1 no.1
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• pp.6.1-6.4
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• 2011

For cancer patients undergoing radiation therapy (RT) or systemic chemotherapy (CHT), cancer-related fatigue (CRF) is a common problem that can negatively impact their quality of life. Guarana (Paullinia cupana) is a plant native to the Amazon basin that has been used as a stimulant since pre-Columbian times. PURPOSE: To evaluate the effectiveness of guarana extract on fatigue in BC patients undergoing either CHT or RT. A total of 137 cancer patients (85% with Breast Cancer) undergoing either CHT (101) or RT (36) were randomized to receive either a placebo or guarana. In all 3 studies, the guarana was given as an unmanipulated dry extract at a dose of 75 mg PO QD in the first two studies or 50 mg PO BID in the third study. Patients were crossed over to the other experimental arm, and we evaluated fatigue with the Chalder Scale in all three studies. Guarana significantly improved the The Chalder Scale Global Scores (- 0.85; 95% CI:-1.31 to -0.40; p = 0.0002); Physical Fatigue Scores (-0.44; 95% CI: - 0.74 to - 0.13; p = 0.005) and Mental Fatigue Scores (-0.93; 95% CI: - 1.14 to - 0.72; p < 0.00001). Guarana did not produce any CTCAE grades 3 or 4 toxicities in any of the studies. Guarana is an effective, cheap and non-toxic alternative for the treatment of fatigue in cancer patients undergoing treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7837-7841
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• 2015

Objective: To assess the safety of Liena polypeptide injection (produced by JILIN FSENS PHARMACEUTICAL CO.,LTD) combined with chemotherapy in treating patients with advanced cancers. Method: A consecutive cohort of patients with advanced cancers were treated with Liena polypeptide injection combined with chemotherapy. And chemotherapy for patients with advanced cancers were adopted from regimens suggested by NCCN guideline. Liena polypeptide injection was intravenously injected at a dosage of 2ml plus 100ml normal saline for continuous 7 days during chemotherapy as one course. After at least two courses of treatment, safety and side effects were evaluated. Results: There were 20 female and 14 male patients with advanced cancer recruited into this study, including 10 patients with breast, 8 patients with colorectal, 8 patients with lung, 4 patients with gastric, and 1 patient with esophageal cancer, as well as 1 patient with non-Hodgkin's lymphoma, 1 patient with low pharyngeal and 1 patient with urethral cancer. The median age of patients was 59 (40-82) years. Incidences of Grade 1 to 2 myelosuppression was observed in 5/34 patients, and Grade 1 to 2 elevation of hepatic enzyme was recorded in 3/34 patients. Adverse effects on the gastrointestinal tract were documented in 5/34 patients, and were Grade 1. No Grade 3-4 toxicities were diagnosed. No treatment related death was found. Conclusions: Liena polypeptide injection combined with chemotherapy was safe in treating several sites of tumors, that mainly included lung, colorectal and breast cancer. However, further study should be conducted to clarify the effectiveness of this treatment.