• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.119-119
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• 1997

Valacyclovir is a L-valyl ester prodrug of acyclovir which is a highly effective and selective antiviral agent in the treatment of herpes virus diseases. Valacyclovir is rapidly and almost completely converted to acyclovir and increases the oral bioavailability of acyclovir three to five fold. However, the intestinal absorption mechanism of valacyclovir is not clear. If the improved absorption mechanism of valacyclovir is fully understood, it will provide a rationale of designing the amino acid ester prodrugs of polar drugs containing hydroxyl group. The main objective of our present study is to characterize the membrane transport mechanism of valacyclovir. Methods : Intestinal absorption of valacyclovir was investigated by using in-situ rat perfusion study and its wall permeability was estimated by modified boundary layer model. The membrane transport mechanism was also investigated through the uptake study in Caco-2 cells and in CHO-hPepTl cells. Results : In the rat perfusion study, the wall permeability of valacyclovir was ten times higher than acyclovir and showed concentration dependency, Valacyclovir also demonstrated a D,L stereo-selectivity with L-isomer having an approximately five-fold higher permeability than D-isomer. Mixed dipeptides and cephalexin, which are transported by dipeptide carriers, strongly competed with valacyclovir for the intestinal absorption, while L-valine did not show any competition with valacyclovir. This indicated that the intestinal absorption of valacyclovir could be dipeptide carrier-mediated. In addition, the competitive uptake study in Caco-2 cells presented that dipeptides reduced the valacyclovir uptake but valine did not. Also, in IC$\sub$50/ study, valacyclovir showed strong inhibition on the $^3$H-gly-sar uptake in CHO-hPepTl cells over-expressing a human intestinal peptide transporter. Taken together, the result from our present study indicated that valacyclovir utilized the peptide transporter for the intestinal absorption.

• Journal of Pharmaceutical Investigation
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• 제23권3호
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• pp.139-144
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• 1993

Microencapsulation of acyclovir, an effective antiviral agent which acts as a specific inhibitor of herpes DNA polymerase, by carbopol-gelatin complex coacervation has been carried out to develop an oral controlled release preparation, which could improve the absorption characteristics in GI tract. After dissolving carbopol and gelatin separately in distilled water at $40^{\circ}C$, gelatin solution was mixed with carbopol solution while stirring at the same temperature. The pH of the mixture was lowered gradually by dropwise addition of 10% HCI with continuous stirring, and then, at pH 3.5, positively charged gelatin molecules were attracted to negatively charged carbopol. These coacervation processes were observed by optical microscopy during preparation. Plasma concentrations of acyclovir in rats after an oral administration of microcapsule suspension were assayed by HPLC, and pharmacokinetic parameters were calculated based on the model-independent analyses. Two standard formulations, oral solution and intravenous bolus injection, were used as references to compare the bioavailability. It has been revealed that $C_{max}$, $T_{max}$, and MRT of microcapsule suspension were greater than those of oral solution, which results in about two-fold increases in bioavailability. Therefore, in conclusion, the carbopol-gelatin microcapsule of acyclovir might be evaluated as an effective oral controlled release preparation which could increase the bioavailability of acyclovir.

• Journal of Yeungnam Medical Science
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• 제3권1호
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• pp.209-213
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• 1986

소아만성B형간염 환아 24명에게 항virus제인 ribavirin을 15mg/kg/day로 14일간 경구투여한 군과 투여하지 않은 대조군으로 나누어 12개월간 혈청 HBsAg과 HBeAg을 추적 검사한 결과 두군 모두에서 HBsAg과 HBeAg의 감소를 볼 수 없었으므로 ribavirin의 소아만성B형간염에 대한 치료효과는 없는것으로 보여진다. 또한 ribavirin 치료에 따른 특별한 부작용도 볼 수 없었다.

• Journal of Microbiology and Biotechnology
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• 제27권6호
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• pp.1189-1197
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• 2017

Lichen-forming fungi are known to have various biological activities, such as antioxidant, antimicrobial, antitumor, antiviral, anti-inflammation, and anti proliferative effects. However, the immunosuppressive effects of Bryoria sp. extract (BSE) have not previously been investigated. In this study, the inhibitory activity of BSE on the proliferation of $CD8^+$ T cells and the mixed lymphocytes reaction (MLR) was evaluated in vitro. BSE was non-toxic in spleen cells and suppressed the growth of splenocytes induced by anti-CD3. The suppressed cell population in spleen cells consisted of $CD8^+$ T cells and their proliferation was inhibited by the treatment with BSE. This extract significantly suppressed the IL-2 associated with T cell growth and $IFN-{\gamma}$ as the $CD8^+$ T cell marker. Furthermore, BSE reduced the expression of the IL-2 receptor alpha chain ($IL-2R{\alpha}$) on $CD8^+$ T cells and CD86 on dendritic cells by acting as antigen-presenting cells. Finally, the MLR produced by the co-culture of C57BL/6 and MMC-treated BALB/c was suppressed by BSE. IL-2, $IFN-{\gamma}$, and CD69 on $CD8^+$ T cells in MLR condition were inhibited by BSE. These results indicate that BSE inhibits the MLR via the suppression of $IL-2R{\alpha}$ expression in $CD8^+$ T cells. BSE has the potential to be developed as an anti-immunosuppression agent for organ transplants.

• Journal of Acupuncture Research
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• 제18권1호
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• pp.237-247
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• 2001

Background : infection associated with otalgia, herpetic eruptions, facial palsy, trigeminal pain and cochleovestibular dysfunction such as hearing dishubance, tinnitus, vertigo and other symptoms, and is not frequently encountered in otolaryngologic field. And facial paralysis occured by this syndrome is rapid in onset, usually severe in degree, and poor in prognosis. Objectives : To evaluate the Oriental Medicine's treatment and prognosis of Herpes zoster oticus and to classify of peripheral Facial palsy on Oriental Medicine. Methods : Clinical observation and analysis about a case of Ramsay-Hunt syndrome III type was done, who visited Dongguk University Gangnam Hospital. This case is managed by integrated therapy of oriental and western medicine. In oriental medicine, to treate ear pain, heonggae-yeongoetang(荊芥蓮翹湯) was given and to treat herpetic eruption, 8 constitution acupuncture treatement was done. In western medicine, antiviral agent, acyclovir and steroid hormone, prednisolon were treated. Result : About 6 weeks treatment, this case which has worse prognosis than Bell's palsy, was completed cured without any complication. Conclusion : 1. Futher divided classification about non-infectious and infectious facial palsy include "Ramsay Hunt Syndrome" is needed. 2. In acute state, Jeonyohwadan's (纏腰火丹) treatement can be applied, but the difference of invasion part, primary symptom such as ear pain and herpetic eruption is needed another treatment. 3. Ear pain and herpetic eruption can be treated in part of poongyeol(風熱) and subyeol(濕熱). 4. In Acupuncture treatement, Jeonyohwadan's (纏腰火丹) treatement can be applied in acute stage and guanwasa's treatement can be applied in chronic stage. but futher research is needed. 5. This case, Ramsay Hunt Syndrome IlI type, was managed by integrated therapy such as heonggae-yeongoetang(荊芥蓮翹湯), 8 constitution acupuncture treatement, acyclovir and prednisolon and this treatement was good effect.

• 대한화장품학회지
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• 제35권4호
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• pp.277-285
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• 2009

본 연구는 연교를 함유한 한방처방단을 이용하여 항염 소재를 개발하여 피부 진정 및 여드름, 아토피용 한방화장품 소재를 개발하고자 하였다. 한방에서 염증 질환 치료에 이용되고 있는 연교를 함유한 처방단을 기성한의서를 바탕으로 조사하였다. 그 중 아토피 증상과 가장 연관이 있을 것으로 판단되는 연교승마탕(連翹升麻湯), 연교음(連翹飮), 청열소독음(淸熱消毒飮), 회춘양격산(回春凉膈散)의 처방단을 추출하여 항산화 및 항염 관련 효능을 알아보았다. 연교 함유처방단들의 자유라디칼 소거활성과 superoxide dismutase 유사활성을 알아보았으며, lipoxygenase 활성 저해 효과와 대식세포주에서의 LPS 처리에 의해 유도되어지는 nitric oxide (NO)와 prostaglandin $E_2$ ($PGE_2$)의 생성을 저해하는 효능을확인하였다. 그 결과 연교 함유 처방단들의 우수한 항산화효과와 lipoxygenase 활성 저해 효과를 확인하였다. 특히, 연교승 마탕과 회춘양격산의 NO와 $PGE_2$의 생성 억제 효과를 확인하였다. 또한, 인체 피부 일차자극시험 결과 무자극으로 나타났다. 이로써, 연교를 함유한 처방단들은 항염 효능을 이용한 피부 자극 완화제로서의 개발 가능성을 확인하였다.

• Journal of Microbiology and Biotechnology
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• 제17권9호
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• pp.1513-1520
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• 2007

[ ${\beta}$ ]-1,3-Glucans enhance immune reactions such as antitumor, antibacterial, antiviral, anticoagulatory, and wound healing activities. ${\beta}$-1,3-Glucans have various functions depending on the molecular weight, degree of branching, conformation, water solubility, and intermolecular association. The molecular weight of the soluble glucan was about 15,000 as determined by a high-performance size exclusion chromatography. From the infrared (IR) and $^{13}C$ NMR analytical data, the purified soluble glucan was found to exclusively consist of ${\beta}$-D-glucopyranose with 1,3 linkage. We tested the immunestimulating activities of the soluble ${\beta}$-1,3-glucan extracted from Agrobacterium sp. R259 KCTC 1019 and confirmed the following activities. IFN-$_{\gamma}$ and each cytokines were induced in the spleens and thymus of mice treated with soluble ${\beta}$-1,3-glucan. Adjuvant effect was observed on antibody production. Nitric oxide was synthesized in monocytic cell lines treated with ${\beta}$-1,3-glucan. The cytotoxic and antitumor effects were observed on various cancer cell lines and ICR mice. These results strongly suggested that this soluble ${\beta}$-1,3-glucan could be a good candidate for an immune-modulating agent.

• Journal of Pharmaceutical Investigation
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• 제24권2호
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• pp.73-83
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• 1994

Applications of liposomes as a drug carrier for the oral delivery of poorly-absorbable macromolecular drugs have been limited, because of their instability in gastrointestinal environments including pH, bile salts, and digestive enzymes. Two polysaccharides, dextran(DX) and pullulan(PL), were introduced to the preformed liposomes in order to enhance the stability. Palmitoyl derivatives of polysaccharides, palmitoyldextran(PalDX) and palmitoylpullulan(PalPL), were synthesizd and introduced to the liposomes during preparation for the same purpose of stability. The effects of these polysaccharides coating were evaluated basically by physical properties of particle size distribution and optical microscopy, then compared with uncoated liposomes by the observations of both in vitro stability and in vovo absorption characteristics. The geometric mean diameters of polysaccharide-coated liposomes were greater than that of uncoated liposome, showing the outermost polysaccharide-coated layer under the optical microscopy. In vitro stabilities of uncoated or polysaccharides-coated liposomes were measured by turbidity changes in various pH buffer solutions containing sodium choleate as bile salts. While uncoated liposome was very sensitive to bile salts, polysaccharides-coated liposomes were stable in relatively higher concentrations of sodium choleate, giving the results of better stability of PalDX- and PalPL-coated liposomes than that of DX- and PL-coated liposomes. After liposomal encapsulation of acyclovir(ACV), an antiviral agent as a model drug, it has been administered orally to rats as dose of ACV 40 mg/kg. Plasma concentrations of ACV were assayed by HPLC and analyzed by model-independent pharmacokinetics. Pharmacokinetic parameters of Cmax, tmax, and [AUC] have been compared.

• Biomolecules & Therapeutics
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• 제23권4호
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• pp.345-349
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• 2015

Betulinic acid, a pentacyclic triterpene isolated from Jujube tree (Zizyphus jujuba Mill), has been known for a wide range of biological and medicinal properties such as antibacterial, antimalarial, anti-inflammatory, antihelmintic, antinociceptive, and anticancer activities. In the study, we investigated the antiviral activity on influenza A/PR/8 virus infected A549 human lung adenocarcinoma epithelial cell line and C57BL/6 mice. Betulinic acid showed the anti-influenza viral activity at a concentration of $50{\mu}M$ without a significant cytotoxicity in influenza A/PR/8 virus infected A549 cells. Also, betulinic acid significantly attenuated pulmonary pathology including increased necrosis, numbers of inflammatory cells and pulmonary edema induced by influenza A/PR/8 virus infection compared with vehicle- or oseltamivir-treated mice in vivo model. The down-regulation of IFN-${\gamma}$ level, which is critical for innate and adaptive immunity in viral infection, after treating of betulinic acid in mouse lung. Based on the obtained results, it is suggested that betulinic acid can be the potential therapeutic agent for virus infection via anti-inflammatory activity.

• 한국축산식품학회지
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• 제28권4호
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• pp.512-516
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• 2008

To search for anit-H5N1 influenza virus agent, the anti-viral activity of methanol and aqueous extracts from thirty medicinal plants were examined in this study. The plant material (30 g) was extracted with methanol (300 mL) for 24 hr at room temperature. Methanol extracts were filtered and evaporated, then freeze-dried. Aqueous extracts were prepared with dried plant material (30 g) and hot distilled water (300 mL). After 3 hr, the aqueous extracts were filtered and evaporated, then lyophilized. Extracts prepared from different plants were tested the antiviral activity against influenza viruses [A/vietnam/1194/04 (H5N1)-NIBRG-14] using the hemagglutination (HA) assay. Among the test plants, Asarum sieboldii was found to be a potent inhibitor of H5N1 influenza virus in MDCK cell culture. Virus titers were 7 log, whereas with methanol extract of Asarum sieboldii for 48 hr titers were 3 log, indicating that methanol extract of Asarum sieboldii inhibited the H5N1 influenza viruses from the infected cells.