• Biomolecules & Therapeutics
• /
• v.25 no.1
• /
• pp.80-90
• /
• 2017

Initial discovery on sphingosine 1-phosphate (S1P) as an intracellular second messenger was faced unexpectedly with roles of S1P as a first messenger, which subsequently resulted in cloning of its G protein-coupled receptors, $S1P_{1-5}$. The molecular identification of S1P receptors opened up a new avenue for pathophysiological research on this lipid mediator. Cellular and molecular in vitro studies and in vivo studies on gene deficient mice have elucidated cellular signaling pathways and the pathophysiological meanings of S1P receptors. Another unexpected finding that fingolimod (FTY720) modulates S1P receptors accelerated drug discovery in this field. Fingolimod was approved as a first-in-class, orally active drug for relapsing multiple sclerosis in 2010, and its applications in other disease conditions are currently under clinical trials. In addition, more selective S1P receptor modulators with better pharmacokinetic profiles and fewer side effects are under development. Some of them are being clinically tested in the contexts of multiple sclerosis and other autoimmune and inflammatory disorders, such as, psoriasis, Crohn's disease, ulcerative colitis, polymyositis, dermatomyositis, liver failure, renal failure, acute stroke, and transplant rejection. In this review, the authors discuss the state of the art regarding the status of drug discovery efforts targeting S1P receptors and place emphasis on potential clinical applications.

• Journal of Pharmaceutical Investigation
• /
• v.31 no.3
• /
• pp.181-184
• /
• 2001

The purpose of this study was to develop transdermal drug delivery system (TDDS) for the combination of physostigmine and procyclidine. The effects of various pressure sensitive adhesives (PSA) on the percutaneous absorption of procyclidine across hairless mouse skin were evaluated to select an appropriate PSA. In addition, the influences of various vehicles on the percutaneous absorption of procyclidine from PSA matrix across hairless mouse skin were evaluated using flow-through diffusion cell system at $37^{\circ}C$. Physostigmine did not have any influence on the permeation rate of procyclidine. The flux of procyclidine was the highest in silicone and PIB and was relatively lower in SIS, Acryl, and SBS adhesive matrices, however, their use was limited by the crystallization of the drug in the matrix. Among acrylic adhesives, the permeability of procyclidine was the highest from poly (ethylene oxide) grafted acrylic adhesive. Some enhancers show different enhancing effect depending on the drug, however, many of the tested enhancers showed enhancing effect for the permeation of both procyclidine and physostigmine to some extent. $Crovol^{\circledR}$ EP 40 showed the highest enhancing effect on the permeation of both compounds. The size of TDDS to provide required permeation rate was estimated to be $35\;cm^2$ based on available information.

• Biomolecules & Therapeutics
• /
• v.26 no.3
• /
• pp.313-321
• /
• 2018

Anti-cancer drug resistance is a major problem in colorectal cancer (CRC) research. Although several studies have revealed the mechanism of cancer drug resistance, molecular targets for chemotherapeutic combinations remain elusive. To address this issue, we focused on the expression of cellular prion protein ($PrP^C$) in 5-FU-resistant CRC cells. In 5-FU-resistant CRC cells, $PrP^C$ expression is significantly increased, compared with that in normal CRC cells. In the presence of 5-FU, $PrP^C$ increased CRC cell survival and proliferation by maintaining the activation of the PI3K-Akt signaling pathway and the expression of cell cycle-associated proteins, including cyclin E, CDK2, cyclin D1, and CDK4. In addition, $PrP^C$ inhibited the activation of the stress-associated proteins p38, JNK, and p53. Moreover, after treatment of 5-FU-resistant CRC cells with 5-FU, silencing of $PrP^C$ triggered apoptosis via the activation of caspase-3. These results indicate that $PrP^C$ plays a key role in CRC drug resistance. The novel strategy of combining chemotherapy with $PrP^C$ targeting may yield efficacious treatments of colorectal cancer.

• Korean Journal of Pharmacognosy
• /
• v.12 no.3
• /
• pp.119-124
• /
• 1981

In our country, in order to cure diseases, a large number of crude drug preparations has been available. Nevertheless, the development of crude drug preparations have been inhibited, because the quality control is not completed so far. Therefore, we have eontinued on studing the quality control method by Zig-zag TLC. profile analysis. The water extract of 'Samyo-Tang' and componental crude drug (Glycyrrhizae Radix, Ephedrae Herba, Armenicae Semen) were developed on Silica gel $60F_{254}\;plate\;(E.\;Merck)$ useing elution solvent. The developed plate were examined useing Dual Wavelength Zig-zag Scanner (Shimadzu). According to the results of the experiment, it could be summarized as follow: 1) Original patterns of TLC profiles of 'Samyo-Tang' componental crude drug and mixing two crude drugs of 'Samyo-Tang' were observed. 2) Original patterns TLC profile of each extract after spraying with 2% ninhydrine were observed. 3) In the extract of addition and subtraction of Ephedrae Herba, peak area of Rf 0.48 and Rf 0.60 were varied quantitatively.

• Journal of the Korean Chemical Society
• /
• v.56 no.4
• /
• pp.473-477
• /
• 2012

The novel chitosan-based thermosensitive hydrogels were prepared as control-releasing drug carriers. N-carboxyethyl chitosan (ACS) was synthesized by microwave heating for 1 h through Michael addition of CS to acrylic acid in a grafting yield of 52.97%, which was proved to be a faster and more efficient way than ordinary methods. 5-Fu was modified with formaldehyde to synthesize N,N'-Bis(hydroxymethyl)-5-fluorouracil (5-Fu-OH). Then an esterification was performed using ACS and 5-Fu-OH to give 5-Fu-ACS. The new thermosensitive hydrogels were prepared by adding sodium glycerophosphate to the solution of compounds under a certain constant temperature. Simultaneously, the hydrogels' swelling rate, in vitro drug release rate and thermosensitive were studied, and found that the 5-Fu-ACS composite hydrogel had more excellent releasing effect, higher drug loading and better thermosensitive.

• Herbal Formula Science
• /
• v.12 no.1
• /
• pp.123-130
• /
• 2004

Aconiti Root(AR), has been used for about 2000 years, since recorded for low grade in 'Shinnongbonchokyung(Divine Husbandman's Herbal Foundation canon)'. It also recorded for Poisonous Drug in 'Myunguibyullok', 'Yaksungron', etc, and they advised when the AR is using for clinical desease it has to be processed. There are more than 13 processing methods, in records that related 39 parts which is recorded in ancient documents. In China, there are no standard of herb that using for clinical, cause of the traditional processing methods was cut since 1960s. In these days, they are using AR that recorded in Aconiti Tuber part of the processing records, in Guangdong and Shantung. In addition, the modification of Processed Aconiti Root(PAR) is also used for goods in Hongkong, Macao, and Southeast Asia. We studied the PAR for enhancing the importance of it, and multiply using. In this study, we search for the history of processing of AR, traditional theories of processing and clinical adaptation.

• Macromolecular Research
• /
• v.13 no.1
• /
• pp.54-61
• /
• 2005

We prepared temperature-sensitive liposomes (TS-liposomes) modified with a thermo sensitive polymer, such as poly(N-isopropylacrylamide) (PNIPAAm), to increase the degree of drug release from liposomes at the hyperthermic temperature. A PNIPAAm hydrogel containing TS-Iiposomes was also prepared to obtain a hydrogel complex at body temperature. In addition, a depot system for local drug delivery using the polymer hydrogel was developed to enhance therapeutic efficacy and prevent severe side effects in the whole body. The PNIPAAm-mod­ified TS-liposome was fixed into the PNIPAAm hydrogel having a high temperature-sensitivity. The release behavior of calcein, a model drug, from TS-liposomes in the PNIPAAm hydrogel was then initiated by external hyperthermia; the results indicated that sustained release as a function of temperature and time was caused by the thermosensitivity of the liposome surface and diffusion of the drug into the PNIPAAm hydrogel. Our results indicated that TS-liposomes in a PNIPAAm hydrogel represented a plausible system for local drug delivery.

• Journal of Pharmaceutical Investigation
• /
• v.19 no.2
• /
• pp.99-107
• /
• 1989

In order to develop a pediatric liquid preparation with sustained release properties, dextromethorphan hydrobromide (DEXT) was complexed with strong cation exchange resin (CG 120) and the-complex was coated with Eudragit RS using a phase separation method by non-solvent addition. The effect of pH, ionic strength of the release medium and drug/resin ratio on the release rate of DEXT was studied. The release rate of free drug from the uncoated complex, and coated complexes with 9.5 and 18.5% Eudragit RS in artificial gastric juice were measured. The release rate from the uncoated complex was faster with higher pH, higher ionic strength of the release medium and higher drug/resin ratio. The release rate from the coated complex could be controlled by the amount of coating material, and the surface after release did not rupture into.

• Korean Journal of Veterinary Service
• /
• v.15 no.1
• /
• pp.81-88
• /
• 1992

This study was conducted to determine the microorganisms inhabitating in sow genital organs and their anti-microbial drug susceptibility During the period between February, 1991 and November 1991, 128 sow genital organs were sampled at six abattoirs. Gross pathological examination and bacterial isolation and identification were performed from the genital organ. In addition, antimicrobial drug susceptibility for the major organisms isolated were examined. 1. Among the bateria isolated from normal genital organs, E. coli(30.7%) Stahylococcus spp.(29.4%), Corynebarterium pyogenes(C. pyogenes) (14.7%), Streptococcus spp.(13.3%) were most freqently isolated, whereas the genera of Klebsiella, Actinobacillus, and Serratia were detected less freqently. 2. Among the bacteria isolated from abnormal genital organs, C. pyogenes,(37.7%), Stahylococcus spp.(30.2%), Proteus spp. (26.4%) , Pasteurella spp. (18.9%) , Steptococcus spp. (9.4%) were most freqently isolated whereas the genera of Pseudomonas, Serratia and Klebsiella were detected less freqently. 3. From sow genital organs showing lesion of endometritis and purulent endometritis C. pyogenes were most freqently isolated, the isolation rate being 67.7％ and followed by Stahylococcus spp., E. coli, Proteus spp., Steptococcus spp. and Pasteurella spp. in the order. 4. Antimicrobial drug susceptibility of the major organisms showed that all the isolates were susceptible to cephalothin, ampicillin, chloramphenicol and sulfamethoxazole / trimethoprim, but resistant to penicillin and streptomycin.

• Carbon letters
• /
• v.27
• /
• pp.18-25
• /
• 2018

In this study, graphene oxide(GO) was used as drug carriers to amorphize poorly watersoluble drugs via a co-spray drying process. Two poorly water-soluble drugs, fenofibrate and ibuprofen, were investigated. It was found that the drug molecules could be in the graphene nanosheets in amorphous or nano crystalline forms and thus have a significantly enhanced dissolution rate compared with the counterpart crystalline form. In addition, the dissolution of the amorphous drug enwrapped with the graphene oxide was higher than that of the amorphous drug in activated carbon (AC) even though the AC possessed a larger specific surface area than that of the graphene oxide. The amorphous formulations also remained stable under accelerated storage conditions ($40^{\circ}C$ and 75% relative humidity) for a study period of 14 months. Therefore, graphene oxide could be a potential drug carrier and amorphization agent for poorly water-soluble drugs to enhance their bioavailability.