• Archives of Pharmacal Research
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• 제26권4호
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• pp.264-269
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• 2003

5-Aminosalicylic acid (5-ASA) is an active ingredient of therapeutic agents used for Crohn s disease and ulcerative colitis. Because it is absorbed rapidly and extensively in the upper intestine, delivery of the agent specifically to the colon is necessary. We selected taurine as a colon-specific promoiety and designed 5-aminosalicyltaurine (5-ASA-Tau) as a new colon-specific prodrug of 5-aminosalicylic acid (5-ASA). It was expected that introduction of taurine would restrict the absorption of the prodrug and show additive effect to the anti-inflammatory action of 5-ASA after hydrolysis. 5-ASA-Tau was prepared in good yield by a simple synthetic route. The apparent partition coefficient of 5-ASA-Tau in 1-octanol/pH 6.8 phosphate buffer or $CHCl_3$/pH 6.8 phosphate buffer was 0.10 or 0.18, respectively, at $37^{\circ}C$. To determine the chemical and biochemical stability in the upper intestinal environment, 5-ASA-Tau was incubated in pH 1.2 and 6.8 buffer solutions, and with the homogenates of tissue and contents of stomach or small intestine of rats at $37^{\circ}C$. 5-ASA was not detected from any of the incubation medium with no change in the concentration of 5-ASA-Tau. On incubation of 5-ASA-Tau with the cecal and colonic contents of rats, the fraction of the dose released as 5-ASA was 45% and 20%, respectively, in 8 h. Considering low partition coefficient and stability in the upper intestine, 5-ASA-Tau might be nonabsorbable and stable in the upper intestine. After oral administration, it would be delivered to the colon in intact form and release 5-ASA and taurine. These results suggested 5-ASA-Tau as a promising colon-specific prodrug of 5-ASA.

• 환경생물
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• 제21권2호
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• pp.164-169
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• 2003

유기주석화합물은 농업과 산업분야에서 많이 쓰이고, 이들은 수계환경으로 유입되어 물이나 저질 중의 세균들에 의해 분해되어 최종적으로는 무기주석으로 된다. Trialkyltin 화합물이 해양생물에 미치는 영향에 관해서는 많은 연구가 있지만, 해양생태계에서 기초적인 생산을 담당하는 플랑크톤류에 미치는 영향에 관해서는 잘 알려져 있지 않다. 본 연구에서는 TBT와 TPT의 분해물인 DBT, MBT, DPT, MPT를 비롯하여 trimethyltin(TMT)과 그분해물인 dimethyltin (DMT)이 기수산 rotifer의 생존에 미치는 독성(96hr-$LC_{50}$)을 조사.비교하였다. 그 결과, DPT(13.8ppb)가 가장 강했으며 TMT(42.9), DBT(80.6), MPT(262.2), MBT와 DMT(>1,000)의 순으로 나타났다. 즉, trialkyltin과 dialkyltin에서는 페닐주석, 부칠주석, 메칠주석의 순으로 독성이 약해지며, mo-noalkyltin에서도 페닐주석화합물이 메칠주석화합물에 비해 독성이 강하다는 것을 확인할 수가 있었다. 이렇듯 독성이 서로 다른 것은 유기주석화합물의 소수성(lipo-philicity)과도 높은 상관이 있었다.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2002년도 생물공학의 동향 (X)
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• pp.112-115
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• 2002

본 연구에서는 균주의 배양과 동시에 생산물을 회수할 수 있는 동시추출공정을 건조질량의 $15{\sim}75$ %의 탄화수소를 생산한다고 알려진 B. braunii 배양에 적용하고자 한다. 일반적인 tow-phase 동시 추출공정의 적용시 B. braunii의 경우 생산된 탄화수소가 균주 외벽의 matrix에 강하게 부착되어 있기 때문에, two phase 추출공정 적용시 bubble solumn내에서 단지 폭기에 의한 교반만으로는 충분한 탄화수소의 회수율을 얻을 수가 없었다. 본 연구에서는 배양액과 유기용매층의 접촉기회를 증대시킨 two-stage 동시추출 공정을 개발하여 기존의 two-stage 동시추출 공정보다 2배 이상 높은 57 %의 탄화수소 회수율을 얻을 수가 있었고, 이를 회분배양후 후속분리공정으로 이용할 경우 6시간 추출후 62 %의 회수율을 얻을 수가있었다.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2002년도 추계국제학술대회
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• pp.154-154
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• 2002

Benzoyl peroxide is a High Production Volume Chemical, which is produced about 1,375 tons/year in Korea as of 2001 survey. The substance is mainly used as initiators in polymerization, catalysts in the plastics industry, bleaching agents for flour and medication for acne vulgaris. The substance is one of seven chemicals of which human health and environmental risks are being assessed by National Institute of Environmental Research (NIER) under the frame of OECD SIDS Program. In this study, Quantitative Structure-Activity Relationships (QSAR) is used for getting adequate information on the physical-chemical property and the environmental fate of this chemical. For the assessment of benzoyl peroxide, models such as MPBPWIN for vapor pressure, KOWWIN for octanol/water partition coefficient, HENRYWIN for Henry's Law constant, AOPWIN for photolysis and BCFWN for bioconcentration factor (BCF) were used. These (Q)SAR model programmes were worked by using the SHILES (Simplified Molecular Input Line Entry System) notations. The physical-chemical properties and the environmental fate of benzoyl peroxide were estimated as followed : vapor pressure =0.00929 Pa, Log Kow = 3.43, Henry's Law constant = 0.00000354 atm-㎥/mole at 25 $^{\circ}C$, the half-life of photodegradation = 3 days, bioconcentration factor (BCF) = 92

• 한국물환경학회지
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• 제36권1호
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• pp.48-54
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• 2020

This paper presents a screening protocol for the selection of solvents available for the solvent extraction desalination process. The desalination solvents hypothetically and theoretically require the capability of (1) Forming hydrogen bonds with water, (2) Absorbing some water molecules into its non-polar solvent layer, (3) Changing solubility for water-solvent separation, and (4) Rejecting salt ions during absorption. Similar to carboxylic acids, amine solvents are solvent chemicals applicable for desalination. The key parameter for selecting the potential solvent was the octanol-water partitioning coefficient (Kow) of which preferable value for desalination was in the range of 1-3. Six of the 30 amine solvents can absorb water and have a variable, i.e., temperature swing solubility with water molecule for water-solvent separation. Also, the hydrogen bonding interaction between solvent and water must be stronger than the ion-dipole interaction between water and salt, which means that the salt ions must be broken from the water and only water molecules absorbed for the desalination. In the final step, three solvents were selected as desalination solvents to remove salt ions and recover water. The water recovery of these three solvents were 15.4 %, 2.8 %, 10.5 %, and salt rejection were 76 %, 98 %, 95 %, respectively. This study suggests a new screening protocol comprising the theoretical and experimental approaches for the selection of solvents for the desalination method which is a new and challenges the desalination process in the future.

• Journal of Pharmaceutical Investigation
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• 제31권4호
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• pp.217-224
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• 2001

To develop a novel transdermal delivery system of loxoprofen (LP), a potent antiinflammatory and analgesic agent, the effects of various vehicles and penetration enhancers on the skin permeation of LP from solution formulations were investigated. The permeation rate of LP through excised guinea pig skin was measured using a side-by-side permeation system at $32^{\circ}C$. The solubilities of LP in various vehicles were determined by the equilibrium solubility method, and partition coefficients $(P_c)$ were determined. The solubility of LP increased in the rank order of water & isopropyl myristate (IPM) & glyceryl dicaprylate/dicaprate & propylene glycol dicaprylate/caprate & propylene glycol laurate (PGL) & polyethylene glycol 400 & diethylene glycol monoethyl ether (DGME) & ethanol. n-Octanol-water $P_c$ value was 15.5. Among pure vehicles tested, IPM and PGL showed highest fluxes of $89.9{\pm}5.0$ and $45.4{\pm}0.3\;{\mu}g/cm^2/hr$ from saturated solutions, respectively. However, it was not possible to demonstrate any correlation between the solubility of LP and its permeation rate, indicating the change in the barrier property of the skin and/or carrier mechanisms by vehicles tested. The addition of DGME to IPM or PGL markedly increased the solubility of LP, but the permeation rate did not decrease when the concentration of DGME in the cosolvent was increased upto 40%. The addition of linoleic acid (3%) in the cosolvent slightly increased the permeation rate, but others such as lauroyl sarcosine, fatty alcohols and fatty acids tested did not show enhancing effect. In conclusion, the DGME-IPM or DGME-PGL cosolvent system proved to be a good vehicle to enhance the skin permeation of LP.

• Archives of Pharmacal Research
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• 제26권12호
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• pp.1002-1008
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• 2003

Ferulic acid (3-methoxy, 4-hydroxy cinnamic acid) is a flavoid component possessing antioxidant property. The compound is currently under development as a new drug candidate for the treatment of the dementia. The objective of this preformulation study was to determine the physicochemical properties of ferulic acid. The n-octanol to water partition coefficients of ferulic acid were 0.375 and 0.489 at the pHs of 3 and 10, respectively. Accelerated stability study for ferulic acid indicated that the t 90 value for the drug was estimated to be 459 days at $25^{\circ}C$. Ferulic acid was also found to be unstable under the relative humidity of more than 76%, probably because of the hygroscopic nature of the drug. In order to study compatibility of ferulic acid with typical excipients, potential change in differential scanning calorimetry spectrum was studied in 1: 1 binary mixtures of ferulic acid and typical pharmaceutical excipients (e.g., Aerosil, Avicel, CMC, Eudragit, lactose, PEG, PVP, starch and talc). Avicel, CMC, PVP and starch were found to be incompatible with ferulic acid, indicating the addition of these excipients may complicate the manufacturing of the formulation for the drug. Particle size distribution of ferulic acid powder was in the size range of 10-190 $\mu$m with the mean particle size of 61 $\mu$m. The flowability of ferulic acid was apparently inadequate, indicating the granulation may be necessary for the processing of the drug to solid dosage forms. Two polymorphic forms were obtained by recrystallization from various solvents used in formulation. New polymorphic form of ferulic acid, Form II, was obtained by recrystallization from 1,4-dioxane. The equilibrium solubility for Form I was approximately twice of that for Form II. The dissolution rate of Form II was higher than that of Form I in the early phase (<6 min). Therefore, these physicochemical information has to be taken in the consideration for the formulation of ferulic acid.

• 대한약리학회지
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• 제29권1호
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• pp.157-163
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• 1993

n-Alkanols의 분자적 약리작용기전 탐구에 기초자료를 제공하기 위하여 소의 신선한 대뇌피질로부터 분리한 synaptosomal plasma membrane vesicles (SPMV) 지질 이중층의 측방확산운동에 미치는 n-alkanols의 영향을 형광 probe법으로 검색하였다. n-Alkanols는 SPMV 지질 이중층의 측방확산운동 범위와 속도를 농도 의존적으로 증가시켰고 1-nonanol까지는 탄소수가 두개 증가될 때마다 그 효력은 약 10배 가량 증가되었으나 탄소수 10개인 1-decanol의 효력은 오히려 감소되는 경향을 나타내었다.

• The Korean Journal of Physiology and Pharmacology
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• 제11권3호
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• pp.107-112
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• 2007

Gap junction protein, connexin, is expressed in endothelial cells of vessels, glomerulus, and renin secreting cells of the kidney. The purpose of this study was to investigate the role of gap junction in renin secretion and its underlying mechanisms using As 4.1 cell line, a renin-expressing clonal cell line. Renin release was increased proportionately to incubation time. The specific gap junction inhibitor, 18-beta glycyrrhetinic acid (GA) increased renin release in dose-dependent and time-dependent manners. Heptanol and octanol, gap junction blockers, also increased renin release, which were less potent than GA. GA-stimulated renin release was attenuated by pretreatment of the cells with amiloride, nifedipine, ryanodine, and thapsigargin. GA dose-dependently increased intracellular $Ca^{2+}$ concentration, which was attenuated by nifedipine, nimodipine, ryanodine, and thapsigargin. However, RP-cAMP, chelerythrine, tyrphostin A23, or phenylarsine oxide did not induced any significant change in GA-stimulated increase of intracellular $Ca^{2+}$ concentration. These results suggest that gap junction plays an important role on the regulation of renin release and intracellular $Ca^{2+}$ concentration in As 4.1 cells.

• 대한화학회지
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• 제55권6호
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• pp.1007-1011
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• 2011

숙신산을 시작물질로 Amberlite IR-120을 이용하여 다이옥틸숙시네이트와 무수숙신산을 합성했다. 양이온 교환 수지를 촉매로 사용했을 때, 숙신산과 옥탄올을 이용한 다이옥틸숙시네이트의 합성은 환류조건에서 18시간의 반응 시간이 요구되었고, 무수숙신산의 합성도 숙신산, Amberlite IR-120, isopropenyl acetate의 존재하에 반응을 진행하였을 때, 18 시간이상의 긴 반응 시간이 요구되었다. 그러나, 마이크로파를 이용하게 되면 반응시간은 10분 이내로 획기적으로 줄어 들었다. 80% 이상의 높은 수득률을 유지하는 상태로 촉매는 최소 4회 이상 재사용 할 수 있었다.