• Journal of Pharmaceutical Investigation
• /
• 제35권6호
• /
• pp.453-460
• /
• 2005

4-Aminopyridine (AP) is a potassium channel blocker used in the treatment of neurological disorders such as multiple sclerosis and Alzheimer disease. AP‘s window of therapeutic effect appears to correlate with its plasma halflife (3.5 hours). It demonstrates pH-dependent solubility because of a weakly basic drug. In addition, the resulting release from conventional matrix tablets decreases with increasing pH-milieu of the gastrointestinal tract. The aim of this study is to design sustained release matrix tablet containing AP, overcoming this problem. $Eudragit^{\circledR}$ L 100 (EuL) and sodium alginate were used in an effort to achieve pH independent drug release. The effect of sodium alginate and EuL on drug release from matrix tablet was investigated. The drug release behavior from the different tablets was analyzed by $t_{20%},\;t_{40%},\;t_{60%}$, The exponential diffusion coefficient n, kinetic constant K were calculated according to the Korsmeyer-Peppas equation. The drug release from matrix tablets prepared with sodium alginate was decreased with increasing the content of sodium alginate in pH 7.4 while there is no significant difference in pH 1.2. The exponent n values were determined to be approximately 0.5 and 0.8 respectively, in both pH 1.2 and 7.4. These values indicate diffusion-based anomalous mechanism and erosion-based anomalous mechanism, respectively. The drug release from sodium alginate matrix tablets prepared with solid dispersion of EuL containing drug showed a slow drug release in an acidic medium and a more fast drug release in phosphate medium, compared with sodium alginate matrix tablets prepared with physical mixture. These results may be attributed to the gel forming ability of sodium alginate and pH dependent solubility of EuL. Therefore, sustained-release AP matrix tablets using sodium alginate and EuL were successfully prepared.

• Biotechnology and Bioprocess Engineering:BBE
• /
• 제6권5호
• /
• pp.326-331
• /
• 2001

With the aim of developing of pH-sensitive controlled drug release system, a poly(Llysine) (PLL) based cationic semi-interpenetrating polymer network (semi-IPN) has been synthesized. This cationic hydrogel was designed to swell at lower pH and de-swell at higher pH and therefore be applicable for achieving regulated drug release at a specific pH range. In addition to the pH sensitivity, this hydrogel was anticipated to interact with an ionic drug, providing another means to regulate the release rate of ionic drugs. This semi-IPN hydrogel was prepared using a free-radical polymerization method and by crosslinking of the polyethylene glycol (PEG)-methacrylate polymer through the PLL network. The two polymers were penetrated with each other via interpolymer complexation to yield the semi-IPN structures. The PLL hydrogel thus prepared showed dynamic swelling/de-swelling behavior in response to pH change, and such a behavior was influenced by both the concentrations of PLL and PEG-methacrylate. Drug release from this semi-IPN hydrogel was also investigated using a model protein drug, streptokinase. Streptokinase release was found to be dependent on its ionic interaction with the PLL backbones as well as on the swelling of the semi-IPN hydrogel. These results suggest that a PLL semi-IPN hydrogel could potentially be used as a drug delivery platform to modulate drug release by pH-sensitivity and ionic interaction.

• KSBB Journal
• /
• 제18권2호
• /
• pp.161-164
• /
• 2003

경구 투여가 비교적 어려운 단백질 약물을 생체적합성이 우수하고 생분해성을 가진 펙틴을 이용하여 목적하는 colon에 전달하고자 하였다. 이온결합을 통해 펙틴, 펙틴-알긴산비드를 제조할 수 있었고, 단백질 약물인 BSA를 포함하여 방출을 행한 결과, 비드의 건조온도가 높을수록 방출률이 높은 경향을 보인 반면, 동결건조된 비드가 가장 높은 방출을 나타냈다. 또한, 가교제의 농도를 높게 처리한 비드일수록 방출률이 낮았다. 경구 투여 후 colon에 도달할 것으로 예상되는 5시간 후에 펙틴 분해효소를 처리한 결과, 효소 처리하지 않은 비드에 비해 급격한 방출이 일어났다. 이러한 결과로 colon내에 존재하는 미생물이 분비하는 효소에 의해 펙턴 비드에 포함된 약물이 방출될 것으로 판단된다. 따라서, 경구로 투여된 펙틴 비드 안의 약물이 소화기관에서 안정하게 통과하고 colon에서 방출되어 효과를 나타낼 것으로 판단된다.

• Journal of Preventive Medicine and Public Health
• /
• 제51권1호
• /
• pp.23-32
• /
• 2018

Objectives: To identify the associations of characteristics of the neighborhood environment with substance abuse among clients receiving treatment for drug abuse in Thailand. Methods: A cross-sectional study was conducted of 1128 drug addicts from 28 neighborhoods who were receiving treatment at all 7 compulsory drug detention centers in Thailand. A trained interviewer conducted structured interviews with the subjects about substance use and the perceived neighborhood environment in their community. A multilevel logistic regression model was applied to estimate the effects of the neighborhood environment on substance use. Results: The majority of participants, 53.8% only used methamphetamine pills, 31.3% used other illicit drugs as well as methamphetamine pills, and 14.9% used an illicit drug other than methamphetamine. Three neighborhood characteristics were associated with substance use. A 1-unit increase in the perceived neighborhood cohesion score was associated with a 15% reduction in methamphetamine pill use and an 11% reduction of the use of both methamphetamine pills and another illicit drug. Conversely, a 1-unit increase in perceived neighborhood crime predicted 19 and 14% increases in the use of methamphetamine pills and the use of both methamphetamine pills and another illicit drug, respectively. In addition, a 1-unit increase in the scores for stigma surrounding addiction corresponded to a 25% increase of the use of methamphetamine pills and a 12% increase in the use of both methamphetamine pills and another illicit drug. Conclusions: Substance use among drug addicts was influenced by characteristics of the neighborhood environment. Therefore, prevention and intervention strategies should be designed based on a consideration of the impact of neighborhood context on substance use behaviors.

• 동의생리병리학회지
• /
• 제21권1호
• /
• pp.235-242
• /
• 2007

The effects of Jujubae Fructus and Licorice extracts on the main components of Sijotang Euphorbiae Kansui Radix, Daphinis Genkwa Flos, Euphonrbiae Pekinensis Radix (KWD) treatment [KWD decoction (KWDD) and KWD powder (KWDP)] related toxicities were examined in the kidney and the liver. To select more suitable extract which effectively reduce KWD-treatment related toxicities in the body, blood biochemical and histopathological changes induced by KWD were analyzed in the rats which received treament of KWD + Jujubae Fructus or KWD + Licorice. In the present study, no KWD-treatment related blood biochemical and histopathological change in the liver was detected. However, increase of tubules containing hyaline casts and atrophic tubules in the kidney was detected as the indicators of KWDD treatment related nephrotoxicity. Addition of Jujubae Fructus (KWDDJ) or Licorice (KWDDL) extracts effectively inhibited the nephrotoxcity induced by KWDD treatments. More ameliorated effects were acquired by addition of Jujubae Fructus extract (KWDDJ) than Licorice (KWDDL). In KWDP treatment, there was no significant difference in the number of tubules containing hyaline casts in all drug treated groups compared to normal or control group except for high dose of KWDP. Both of Jujubae Fructurs and Licorice reduced high dose of KWDP treatment related nephrotoxicity, and there was no significant difference between KWDPJs and KWDPLs. It is concluded that addition of Jujubae Fructus is more suitable than Licorice in reducing the nephrotoxicty of KWDD, also it is more suitable to taking Sipjotang in the form of powder than decoction.

• 분석과학
• /
• 제32권1호
• /
• pp.24-34
• /
• 2019

The safety of food is occasionally questionable, as there have been some reports of products contaminated with illegal adulterants. In this study, the presence of 16 sedative-hypnotics and sleep inducers in dietary supplements was determined by ultra-high-performance liquid chromatography with UV detection (UPLC-UV) and quadruple Orbitrap mass spectrometry (Q-Orbitrap-MS). The UPLC method was validated, providing a linearity (R2) of more than 0.999, and LODs and LOQs that ranged from 0.2 to 0.5 and 0.6 to $1.5{\mu}g\;mL^{-1}$, respectively. The repeatabilities were 0.2-8.4 % (intra-day) and 0.3-4.5 % (inter-day), and the accuracies were 89.0-117.0 % (intra-day) and 87.8-111.9 % (inter-day). The mean recoveries of the spiked samples ranged from 98.7 to 107.3 %. The relative standard deviation (%RSD) of the stability was less than 2.4 %. Using the developed method, one sedative-hypnotic compound, phenobarbital, was detected in one of the nineteen samples tested. In addition, the major characteristic fragment ions of each target compound were confirmed using Q-Orbitrap-MS for higher accuracy. Monitoring the presence of these 16 sedative-hypnotics and sleep inducers in dietary supplements should be pursued in the interest of human health, and the results of this study confirmed that the developed method has value for this application.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• 제21권4호
• /
• pp.329-335
• /
• 2018

Loss of response to anti-tumor necrosis factor (anti-TNF) agents in the treatment of inflammatory bowel disease (IBD) is a major consideration to maintain sustained response. Reversal of immunogenicity can re-establish response and increase the durability of these agents. Strategies to reverse immunogenicity include dose-intensification and/or the addition of an immunomodulator. However, there is a relative paucity of data on the efficacy of such interventions in pediatric IBD patients. Available reports have not strictly utilized homogenous mobility shift assay, which reports on anti-drug antibodies even in the presence of detectable drug, whereas prior studies have been confounded by the use of drug sensitive assays. We report four pediatric inflammatory bowel disease patients with successful reversal of immunogenicity on an anti-TNF agent using dose intensification and/or addition of an immunomodulator.

• 약학회지
• /
• 제31권3호
• /
• pp.189-196
• /
• 1987

This study was carried out to investigate the effect of surfactant on the dissolution of relatively hydrophilic drugs, such as sulfanilamide (SF) and sulfacetamide (SFA) granules prepared by wet granulation. The additive incorporated in the granules is starch or microcrystalline cellulose(MCC) as an excipient, PVP as a binder, and polysorbate 80 (P-80) as a surfactant. The dissolution characteristics of SF and SFA granules in distilled water were as follows: The values of T$_{75%}$ were 4.60 and 2.50min, respectively for SF and SFA granules. Incorporation of 0.1% P-80 in SF granule ratarded the dissolution of SF as compared with control, but addition of 0.1% P-80 to SFA granule improved the dissolution of SFA in comparison with control. In SF and SFA granules formulated with either starch or PVP, the release of the drug was increased as compared with control. In SF granule, the dissolution of the drug was further reduced by the inclusion of P-80 in the granule containing starch or PVP. Incorporation of P-80 in SFA granule with starch or PVP affected little on the dissolution of the drug. Addition of a nonswelling excipient, MCC decreased the dissolution rate of SF and SFA granules. as compared with each control. The presence of P-80 in these granules made the dissolution rate slower in comparison with the granules containing only MCC.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권5호
• /
• pp.2087-2092
• /
• 2015

Nowadays herbal-derived medicines are attracting attention as new sources of drugs with few side effects. Silibinin is a flavonoid compound with chemotheraputic effects on different cancers such as examples in the prostate, lung, colon and breast. In the present study, the cytotoxic effects of silibinin on MCF7 breast cancer cells were investigated. Apoptosis was determined by flow cytometry and the impact of silibinin on the expression of pivotal genes including Bak, P53, P21, BRCA1, BCL-X1 and ATM was analyzed. Treatment for 24h had a significant dose-dependent inhibitory effect on cell growth (p<0.05) with dose- and time- dependent induction of apoptosis (p<0.05). In addition, there were significant increases in BRCA1, ATM, Bak and Bcl-XL gene expression at the mRNA level with different concentrations of silibinin for 24 or 48 h (p<0.05). Taken together, the results suggest that silibinin inhibits the proliferation and induces apoptosis of MCF-7 cells by down-regulating Bak, P53, P21, BRCA1, BCL-Xl and thus may be considered as an effective adjuvant drug to produce a better chemopreventive response for the cancer therapy.

• 센서학회지
• /
• 제29권2호
• /
• pp.100-104
• /
• 2020

Thus far, several in vivo biosensing platforms have been proposed to measure the mechanical contractility of cultured cardiomyocytes. However, the low sensitivity and screening rate of the developed sensors severely limit their practical applications. In addition, intensive research and development in cardiovascular disease demand a high-throughput drug-screening platform based on biomimetic engineering. To overcome the drawbacks of the current state-of-the-art methods, we propose a high-throughput drug-screening platform based on 16 functional high-sensitivity well plates. The proposed system simulates the physiological accuracy of the heart function in an in vitro environment. We fabricated 64 cantilevers using highly flexible and optically transparent silicone rubber and placed in 16 independent wells. Nanogrooves were imprinted on the surface of the cantilever to promote cell alignment and maturation. The adverse effects of the cardiovascular drugs on the cultured cardiomyocytes were systematically investigated. The 64 cantilevers demonstrated a highly reliable and reproducible mechanical contractility of the drug-treated cardiomyocytes. Real-time high-throughput screening and simultaneous evaluation of the cardiomyocyte mechanical contractility under multiple drugs verified that the proposed system could be used as an efficient drugtoxicity test platform.