• 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.

• Molecules and Cells
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• 제22권1호
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• pp.97-103
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• 2006

Phosphoinositides are critical regulators of ion channel and transporter activity. There are multiple isomers of biologically active phosphoinositides in the plasma membrane and the different lipid species are non-randomly distributed. However, the mechanism by which cells impose selectivity and directionality on lipid movements and so generate a non-random lipid distribution remains unclear. In the present study we investigated which structural elements of phosphoinositides are responsible for their subcellular location and movement. We incubated phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PI(4)P) and phosphatidylinositol 4,5-bisphosphate ($PI(4,5)P_2$) with short or long acyl chains in CHO and HEK cells. We show that phosphate number and acyl chain length determine cellular location and translocation movement. In CHO cells, $PI(4,5)P_2$ with a long acyl chain was released into the cytosol easily because of a low partition coefficient whereas long chain PI was released more slowly because of a high partition coefficient. In HEK cells, the cellular location and translocation movement of PI were similar to those of PI in CHO cells, whereas those of $PI(4,5)P_2$ were different; some mechanism restricted the translocation movement of $PI(4,5)P_2$, and this is in good agreement with the extremely low lateral diffusion of $PI(4,5)P_2$. In contrast to the dependence on the number of phosphates of the phospholipid head group of long acyl chain analogs, short acyl chain phospholipids easily undergo translocation movement regardless of cell type and number of phosphates in the lipid headgroup.

• Journal of Pharmaceutical Investigation
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• 제29권4호
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• pp.329-335
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• 1999

Clenbuterol, a selective ${\beta}_2-adrenergic$ receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic bronchitis and pulmonary emphysema. For the purpose of developing a transdermal preparation for clenbuterol, we attempted to select an optimal solvent system and permeation enhancer among fatty acids and fatty alcohols which are known to accelerate the penetration of various drugs in permeation experiments using hairless mouse skin and Franz diffusion cell. Apparent partition coefficient of clenbuterol was increased as pH of buffer solution was increased and solubility of clenbuterol was increased as the percent of propylene glycol(PG) in buffer solution(pH 10) was increased. Permeability of clenbuterol from different buffer(pH 10)/PG solvent mixtures was decreased as the percent of PG in pH 10 buffer solution was increased and among the various enhancers studied, lauryl alcohol was found to be the most effective enhancer, increasing the permeability of clenbuterol approximately 76-fold compared with control. Lauryl alcohol$(0{\sim}2%)$ enhanced the permeability of clenbuterol concentration-dependently. In this study, the optimal solvent system for the penetration of clenbuterol was found to be 50/50 buffer(pH 10)/PG solvent mixture containing 2% lauryl alcohol.

• 한국식품과학회지
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• 제22권1호
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• pp.56-60
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• 1990

역류분배 방법을 이용한 단백질의 분리정제 가능성을 높이기 위하여 4가지 모델단백질에 대하여 수용성 액체 2상계에서의 분획계수를 pH 변화에 따라 조사하였다. 또한 역류분배를 이용한 다중분배추출방식으로 모델 단백질의 혼합물을 수준의 pH(4.5-12.0)에서 분획하였다. 그 결과 pH에 따라 단백질들의 등전점 차이로 인한 분획계수(K)값이 다르게 나타서, 다중분배를 행할 때 각 단백질 분획들이 위치하는 튜브번호가 다르게 되므로 역류분배 방법을 통한 단백질의 분리 가능성을 보여주었다.

• Journal of Pharmaceutical Investigation
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• 제27권2호
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• pp.119-123
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• 1997

The physicochemical and structural properties of new capsaicin derivative, DA-5018, were examined. The reference standard of this compound was obtained by the recrystallization. A method for the determination of the dissociation constant of the compound is described. pH-solubility and distribution coefficient were determined by chromatographic method. Fundamental properties on thermal behaviors were investigated by TG, DTA and DSC. Structural analysis based on spectroscopic method coincided with the chemical structure of DA-5018. Approximate dissociation constant of the compound determined by UV spectral method was 9.35. Solubilities and partition coefficients in various pH buffer solution appeared pH-dependency. No crystal transition or further transition was found in the thermal analysis. This compound showed good stability, but pH 13 buffer and acetone made some degradative products.

• 한국지하수토양환경학회지:지하수토양환경
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• 제27권6호
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• pp.47-57
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• 2022

A number of different methods have been used for modeling the sorption of volatile organic chlorinated compounds such as tetrachloroethylene/perchloroethylene (PCE). In this study, PCE was adsorbed in several natural sorbents, i.e., Pahokee peat, vermicompost, BionSoil^®, and natural soil, in the batch experiments. Several sorption models such as linear, Freundlich, solubility-normalized Freundlich model, and Polanyi-Manes model (PMM) were used to analyze sorption isotherms. The relationship between sorption model parameters, organic carbon content (f_oc), and elemental C/N ratio was studied. The organic carbon normalized partition coefficient values (log K_oc = 1.50-3.13) in four different sorbents were less than the logarithm of the octanol-water partition coefficient (log K_ow = 3.40) of PCE due to high organic carbon contents. The log K_oc decreased linearly with log f_oc and log C/N ratio, but increased linearly with log O/C, log H/C, and log (N+O)/C ratio. Both log K_F,oc or log K_F,oc decreased linearly with log f_oc (R² = 0.88-0.92) and log C/N ratio (R² = 0.57-0.76), but increased linearly with log (N+O)/C (R² = 0.93-0.95). The log q_max,oc decreased linearly as log f_oc and log C/N increased, whereas it increased with log O/C, log H/C and log (N+O)/C ratios. The log q_max,oc increased linearly with (N+O)/C indicating a strong dependence of q_max,oc on the polarity index. The results showed that PCE sorption behaviors were strongly correlated with the physicochemical properties of soil organic matter (SOM).

• 약학회지
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• 제34권2호
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• pp.126-132
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• 1990

To enhance the activity of ibuprofen, amides of ibuprofen, 1-piperazinyl-2-(4-isobutylphenyl)propionamide(Ibu-P.A.) and 1-(4-methylpiperazinyl)-2-(4-isobutylphenyl)propionamide (Ibu-M.P.), were synthesized and the pharmaceutical properties and the pharmacological activities of the amides were studied. The lipid:water partition coefficients and pKa values were examined in vitro, and the antiinflammatory effect, analgesic effects, acute toxicity, and intestinal absorption were studied for the amides and compared with ibuprofen in vivo. The results are summarized as belows; 1) The lipid:water partition coefficients of Ibu-M.P. were higher than those of ibuprofen. 2) The calculated pKa values of ibuprofen and Ibu-M.P. were 5.49 and 8.66, respectively. 3) The antiinflammatory effects of ibuprofen, Ibu-P.A., and Ibu-M.P. were same intensity, but the duration of the effects of Ibu-P.A. and Ibu-M.P. were longer than that of ibuprofen. 4) The analgesic effect of Ibu-M.P. was more potent than those of ibuprofen and Ibu-P.A. in the acetic acid-induced writhing test. 5) The $LD_{50}$ was 495 mg/kg for ibuprofen, 187 mg/kg for Ibu-M.P., and over 1250 mg/kg for Ibu-P.A.. 6) The absorption rate constants(k) and half-life($t_{1/2}$) were 0.74($hr^{-1}$) and 0.94(hr) for ibuprofen, and 0.72 ($hr^{-1}$) and 0.96 (hr) respectively for Ibu-M.P..

• 암석학회지
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• 제2권2호
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• pp.63-73
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• 1993

The assemblage epidote and grandite garnet occurs in low-to medium-grade metabasites and calc schists of various geotectonic settings and in hydrothermally altered calcareous rocks in skarn deposits. The compositions of sixteen epidote-garnet paris have been analysed by means of electron microprobe. Al-Fe partitioning between coexisting grandite garnet and epidote is considered and measured at the grain boundaries on the supposition that the surface equilibrium was maintained in the following exchange reaction: 2$Ca_2Al_3Si_3O_12$(OH)+$Ca_3Fe_2Si_3O_12$=2$Ca_2A_l2FeSi_3O_12$(OH)+$Ca_3Al_2Si_3O_12$ Partition coefficients confirms the differences in thermal conditions between low-grade and medium-grade metamorphic rocks. $K_D$ values ($X_{$CO_2$}$=($Fe^{+3}$/Al)$^{Ep}$/($Fe^{+3}$/Al)$^{Gr}$, where Fe=$Fe^{+3}$) from greenschist facies rocks of the estimated metamorphic temperatures, 330~$390^{\circ}C$, range approximately between 0.02 and 0.17. Epidote-amphibolite facies rocks and calcareous skarns of the estimated temperatures, 400~$550^{\circ}C$, have $K_D$ values between 0.24 and 0.37. $K_D$ values from the rocks of the temperatures, 640~$700^{\circ}C$, range nearly between 0.58 and 0.75. The diagrams in Figs. 2 and 3 can serve as a mineralogic thermometer for relatively shallow rocks, assuming that the pressure dependence of partition coefficients for the iron-exchange reaction in the two minerals can be neglected.

• Journal of Pharmaceutical Investigation
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• 제17권4호
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• pp.197-204
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• 1987

Novel pranoprofen algininate and lysinate salts were manufactured and their salt formation was confirmed by melting point, infrared spectroscopy, nuclear magnetic resornance spectroscopy, differential scanning calorimetry and powder X-ray diffractometry. The physical properties of pranoprofen lysinate and argininate salts were compared with those of pranoprofen through in vitro and in vivo tests. Solubility, $pK_a$ and lipid-water partition coefficient were measured through in vitro experiments, while antiinflammatory efficacy, analgesic effect, acute toxicity and in situ absorption were tested through in vivo experiments. The results obtained were as follows: 1) The solubilities of pranoprofen argininate and lysinate salts were increased markedly in pH 6.8 and pH 7.5 phosphate buffer solutions, comparing with that of pranoprofen itself. 2) $pK_a$ values of pranoprofen, pranoprofen argininate and lysinate salts were 6.34, 7.99 and 7.56 in carbon tetrachloride, and 5.86, 6.69 and 7.92 in chloroform, respectively by liquid-liquid partition method. 3) The lipid-water partition coefficients of pranoprofen argininate and lysinate salts were increased more than that of pranoprofen in carbon tetrachloride, chloroform, or benzene-pH 6.8 buffer system, but were nearly identical using pH 1.2 buffer as water phase. 4) Antiinflammatory effects of pranoprofen argininate and lysinate salts were remarkably increased and analgesic effects of the salts were as same as that of pranoprofen. 5) Pranoprofen argininate and lysinate salts were safer than pranoprofen itself in acute toxicity, and the in situ absorption rates of pranoprofen, pranoprofen argininate and lysinate salts were 0.392, 0.960 and $0.762\;hr^{-1}$, respectively according to the rat intestine recirculation experiment.

• Journal of Pharmaceutical Investigation
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• 제22권2호
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• pp.139-148
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• 1992

A prodrug of cefazolin pivaloyloxymethyl ester (CFZ-PV) was synthesized to improve oral absorption and bioavailability of parent drug by esterification of sodium cefazolin (CFZ) with chloromethyl pivalate. The successful synthesis of CFZ-PV was confirmed by spectroscopic analysis. Partition coefficient studies showed that CFZ-PV is more lipophilic than CFZ. The pharmacokinetic characteristics of CFZ-PV and CFZ preparations were compared following oral administrations of these compounds to rabbits. The analysis of CFZ in plasma was conducted by HPLC method. The ester compound (prod rug) was not detected in plasma following oral administration of CFZ-PV, and although CFZ-PV had not microbiological activity in vitro, the plasma taken after CFZ-PV administration had microbiological activity. From above observations, it was noted that CFZ-PV is rapidly hydrolyzed to CFZ in the body. And it was found that the oral absorption of CFZ-PV was increased, yielding 2-fold higher bioavailability than CFZ. From the results of this experiment, it was concluded that CFZ-PV could be a novel prodrug of CFZ which can improve the oral bioavailability of CFZ.