• Archives of Pharmacal Research
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• 제27권6호
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• pp.662-669
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• 2004

The highly water-soluble monomethoxypoly(ethyleneglycol) (mPEG) prod rugs of cyciosporin A(CsA) were synthesized. These prod rugs were prepared by initially preparing intermediate in the form of carbonate at the 3'-positions of CsA with chloromethyl chloroformate, in the pres-ence of a base to provide a 3'-carbonated CsA intermediate. Reaction of the CsA intermediate with mPEG derivative in the presence of a base provides the desired water-soluble prod rugs. As a model, we chose molecular weight 5 kDa mPEG in the reaction with CsA to give water soluble prodrugs. To prove that the prod rug is decomposed in the body to produce CsA, the enzymatic hydrolysis test was conducted using human liver homogenate at $37^{\circ}C$. The prodrug was decomposed in human liver homogenate to produce the active material, CsA, and the hydrolysis half-life ($t_{1/2}$) of the prodrug, KI-306 was 2.2 minutes at $37^{\circ}C$. However, a demon-stration of non-enzymatic conversion in pH 7.4 phosphate buffer was provided by the fact that the half-life ($t_{1/2}$) is 21 hours at 37$^{\circ}C$. The hydrolysis test in rat whole blood was also conducted. The hydrolysis was seen with half-life ($t_{1/2}$) of about 9.9, 65.0, 14.2, 3.4, 2.1 9.5, and 1.6 minutes for KI-306, 309, 312, 313, 315, 316, and 317, respectively. This is the ideal for CsA prodrug. The pharmacokinetic study of the prodrug, KI-306, in comparison to the commer-cial product (Sandimmune Neoral Solution) was also carried out after single oral dose. Each rat received 7 mg／kg of CsA equivalent dose. Especially, the prodrug KI-306 exhibits higher AUC and $C_{max}$ than the conventional Neoral. The AUC and $C_{max}$ were increased nearly 1.5 fold. The kinetic value was also seen with $T_{max}$ of about 1.43 and 2.44 hours for KI-306 and Neoral, respectively.

• Journal of Pharmaceutical Investigation
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• 제14권2호
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• pp.55-61
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• 1984

This investigation was designed to determine the release of fenbufen from suppositories and their bioavailability in rabbits. Suppositories containing fenbufen were made by the fusion method with Witepsol H-15, Wecobee and PEG 1540 base. Displacement value, weight variation, content uniformity, melting point and melting time were determined for preformulation of the fenbufen suppositories. The release rates were determined with the KP dissolution apparatus and with cellophane tube dialysis device and were increased in order of PEG 1540, Witespol H-15 and Wecobee. The bioavailabilities of fenbufen after rectal administration were also increased in order of PEG 1540, Witespol H-15 and Wecobee.

• Archives of Pharmacal Research
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• 제27권8호
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• pp.878-883
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• 2004

Tacrolimus (FK506), which is isolated from Streptomyces tsukubaensis, is a new potent immu-nosuppressant. Because of poor solubility in water, the conventional intravenous dosage forms of tacrolimus contain surfactants such as cremophor EL (BASF Wyandotte Co.) or hydroge-nated polyoxy 60 castor oil (HCO-60) which may cause adverse effects. This study relates to a polymer-tacrolimus conjugate, which can be dissolved in water, formed by chemically binding the sparingly soluble drug, tacrolimus, with the water soluble polymer, methoxypoly(ethylene glycol) (mPEG). Water soluble tacrolimus-mPEG conjugates have been synthesized and shown to be function in vitro as prodrugs. These conjugates are in the form of an ester wherein the 24-, 32- or 24,32-positions are esterified. The desired 24-, 32- or 24,32-esterified com-pounds were obtained by initially acylating of tacrolimus with iodoacetic acid at the 24-,32-, or 24,32-positions and then reacting the resulting acylated tacrolimus with a mPEG in the pres-ence of a base such as sodium bicarbonate. These conjugates were converted again into tac-rolimus by the action of enzymes in human liver homogenate, and the half-lives of the conjugates are approximately 10 min in the homogenate, indicating that the esterified tacroli-mus derivatives may be practically applicable as a prod rug for the immunosuppressant.

• 한국임상약학회지
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• 제8권2호
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• pp.143-146
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• 1998

Acetaminophen (APAP) suppositories with active ingredients, i.e., polyethylene glycol (PEG), Witepsol H-15 (WH), were prepared for hospital use and investigated on their drug release characteristics and pharmacokinetics. WH was employed as oil-soluble base with an aim of reducing fragility and mucosa irritancy that are common drawbacks found in PEG suppositories. Also hollow type suppository was tried as compared with conventional type suppository. Drug release tests revealed that in most formulations, more than $80\%$ of loaded APAP were released within 20 minutes, except for APAP-WH hollow type suppositories. Significant differences in the plasma concentration profile were observed among four type suppositories. $T_{max}$ of APAP-PEG and APAP-WH suppositories were 90 and 60 minutes, respectively, in hollow types. APAP-WH hollow type suppositories demonstrated fast absorption rates of APAP as compared with those of APAP-PEG suppositories. No burst effect was observed from APAP-WH suppository in contrast to APAP conventional type suppository, whereas AUCs of all the suppositories were similar. APAP-WH hollow type suppository may be an useful dosage form for hospital use.

• 대한화장품학회지
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• 제34권1호
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• pp.15-23
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• 2008

본 연구는 유용성 물질 포집에 효과적인 solid lipid nanoparticle(SLN)을 이용하여 수용성물질인 LA-PEG을 새로운 제조방법에 응용하여 실험하였다. 지질로 사용된 오일은 coconut oil, macadamia oil, 그리고 jojoba oil 3가지로 이들의 특징은 생분해성이 강하다. 외부유화제로는 Tween 20, Tween 60을 이용하여 T-SLN을 제조하였으며, SLN의 입자 분포를 비교 분석한 결과 coconut oil을 지질로 하여 사용한 것이 크기가 가장 작았으며 사용한 계면활성제의 양에 따라 입자크기와 분포형태가 달라졌다. 1%의 Tween 60과 macadamia oil을 이용한 베이스가 입자크기가 가장 컸다. 방출관찰결과 coconut oil을 지질로 한 2%의 Tween 20의 베이스가 가장 늦게 방출되었고, 가장 빠른 방출한 것은 Tween 60 2% 베이스였다.

• 한국작물학회지
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• 제35권3호
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• pp.248-253
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• 1990

자운영(Astragalus sinicus L. Line A) 종자의 발아와 묘신장을 네 온도(15, 25, 30 및 35$^{\circ}C$), 세 polyethylene glycol(PGE) 10,000(MW) 용액(0, 20 및 25g/100mg $H_2O$), 그리고 다섯수준의 황산(중량기준 conc. H$_2$SO$_4$ : Seeds; 0, 1:1 10분, 1:1 20분 1:1.5 10분 및 1:1.5 20분 침지)에 처리하여 측정한 결과를 요약하면 다음과 같다. 자운영의 발아율은 15$^{\circ}C$에서 가장 높았으나 묘장은 $25^{\circ}C$에서 가장 길었다. 발아율과 묘장 모두 PEG 무처리에서 25로 농도가 증가할수록 급격히 감소되었다. 15$^{\circ}C$의 PEG 20과 25에서는 다른 온도보다는 높은 발아율을 보였다. 황산처리효과에서는 발아율과 묘장 모두 황산무처리와 같거나 감소되었다. 그러나 PEG 무처리의 경우에는 황산:종자비율 1:1.5에서 10분간 침지시에 발아율이 가장 높았다. 본 시험의 결과로는 종자의 발아는 수분의 영향이 가장 큰 것으로 보였다.

• 대한화학회지
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• 제62권2호
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• pp.87-92
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• 2018

A series of pyrimidine annulated dihydropyrano[2, 3-c]pyrazole derivatives were synthesized and screened for their antimicrobial activity. The precursor, dihydropyrano[2, 3-c]pyrazole was synthesised under catalyst free condition using PEG-400 as reaction medium which facilitated improved yield compared to base catalyzed reaction. Wide scope of substrates, simple workup procedure and high yield even in the absence of catalyst are the major highlights of the protocol. Dihydropyrano[2, 3-c]pyrazoles on condensation with formic acid formed pyrimidine annulated dihydropyrano[2, 3-c]pyrazole derivatives. All the products are characterized using FTIR, $^1H-NMR$ and $^{13}C-NMR$ spectroscopic techniques. The molecules have shown good to moderate activity as antimicrobial agents when compared to the standard drug ciprofloxacin.

• 한국응용과학기술학회지
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• 제29권4호
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• pp.552-560
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• 2012

약물 전달 시스템은 약물의 방출 프로파일, 흡수, 분배 및 제품의 효율성과 안전성, 환자의 편의성과 협조를 향상시키기 위한 제거를 개선하는 명백하게 보호화된 공식화 기술이다. 가장 일반적으로 쓰이는 transdermal 시스템은 다양한 종류의 기술을 사용하는 skin patch다. 다른 투약 방법과 달리, transdermal 시스템은 장기간 사용이 가능하다. 또한, 부작용이 생길 경우, 약물 투약의 중단이 가능하다. karaya gum and locust bean gum(LBG)/water-soluble chitosan oligomer(WSCO)과 같은 Polysaccharide를 TDS의 기본 물질로 선택하였다. 또한, 이 polymers들은 tacrine 물질, 강화제로 규정되어진다. 이러한 polysaccharide 중에서, karaya gum matrix의 침투율은 lipophilic drug in vitro 와 같은 tacrine 내에서 가장 빠르다. 우리는 glycerin, PEG 400, and PEG 800를 강화제로 사용하였다. 그러므로, transdermal의 tacrine 흡수율은 vehicle 구성을 바꿈으로써, 혹은 침투 강화제를 사용함으로써 향상되었을 것이다. 특히, vehicle이 스스로의 효과를 강화하는 것과 더불어, vehicle에 강화제를 첨가함으로써 높은 침투 효율이 얻어질 것으로 기대된다.

• 약학회지
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• 제35권3호
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• pp.197-202
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• 1991

In order to study drug release from the suppository, three types of hollow suppositories and one conventional suppository were prepared using indomethacin(IDM) as a model drug and Witepsol H-15 as a base. The 4 types of suppository prepared are as follows: type I, conventional suppository containing 50 mg of IDM powder, type II, hollow supository containing 50 mg of IDM powder in the cavity, type III, hollow suppository containing 25 mg of IDM powder in the base and IDM microcapsules (25 mg as IDM powder) in the cavity, and type IV, hollow suppository containing IDM microcapsules (25 mg as IDM powder) in the base and 0.5 ml of 5%(w/v) IDM-PEG 300 solution in the cavity. The drug amount released(%) from type II and I within 24 hrs was 46.7% and 66.9%, respectively. Comparing with the drug amount released from four types of suppository within initial 2 hrs and 24 hrs, that of type IV was high as 32.7% and 76.6%, respectively. IDM-ethycellulose microcapsules passed through 270 mesh sieve and the IDM content was 20.95%.

• 박물관보존과학
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• 제7권
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• pp.53-62
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• 2006

경산 임당저습지유적에서 출토된 목제 갑옷틀과 다양한 칠기유물들은 재질이 매우 취약하고 옻칠이 되어 있어 공기 중에 노출되면 건조가 진행되어 곧바로 수축·변형이 일어나기 쉽다. 목제 갑옷틀의 경우 대형으로 동결건조과정 중 융해의 발생우려가 있고 칠기의 경우 목재표면에 옻칠이 되어있어 약제가 잘 침투되지 않고 처리 중 칠막이 부풀거나 탈락될 우려가 높다. 따라서 목제 갑옷틀은 진공 동결건조과정 중 융해방지를 위하여 t-butanol로 치환한 후 최종 PEG#3,350 43%의 t-butanol용액에 함침하고, 칠기는 최종 PEG#3,350 40%의 수용액(水溶液)에 실온에서 함침처리 후 동결 건조하여 보존처리 하였다. 칠기의 칠 도막 분석결과 뚜껑 및 고배는 초칠을 한 후 밑층에 흑색안료(그을음)와 옻칠을 혼합하여 바른 후 2-3회 생칠을 하였고 주칠 컵형목기는 밑층에 흑색안료와 옻칠을 혼합하여 바른 후 그 위에 1회 중칠을 하였으며, 산화철(Fe₂O₃: 석간주)이 붉은 칠의 발색안료로 쓰였을 가능성을 보여준다.