• Journal of Pharmaceutical Investigation
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• 제18권3호
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• pp.99-105
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• 1988

Inclusion complex formation of furosemide with ${\beta}-cyclodextrin({\beta}-CyD)$ in solid state was confirmed by X-ray diffractometry, IR spectroscopy and differential scanning calorimetry (DSC). The solid complexes of ${\beta}-CyD$ with furosemide in molar ratio of 2 : 1 were prepared by solvent evaporation method. The photodegradation of furosemide in alkaline solution under the light and the hydrolysis of furosemide in acidic solution were not inhibited by complex formation with ${\beta}-CyD$. However, the bioavailability of furosemide was improved by complex formation with ${\beta}-CyD$ after oral administration to rats.

• 한국임상약학회지
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• 제8권2호
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• pp.133-138
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• 1998

Phthalimidyl ester of ceftezole (CFZ-PT) was synthesized as a prodrug by esterification of ceftezole (CFZ) with N-bromophthalimide. CFZ-PT was more lipophilic than CFZ when the lipophilicity was assessed by partition coefficients between n-octanol and water at various pH. The pharmacokinetic characteristic of CFZ-PT and CFZ preparations were compared following oral administrations of these compounds to rabbits. CFZ-PT is expected to be metabolized rapidly to CFZ in the body. The metabolism process appears to be hydrolysis of the ester to CFZ, the parent drug of CFZ-PT. In vivo metabolism of CFZ-PT to CFZ was confirmed in rabbit by HPLC analysis. CFZ concentration in the serum samples taken after oral administration of CFZ-PT(equivalent amount of CFZ) were released and higher than those of CFZ. Oral bioavailability of CFZ-PT was 1.9 fold higher than at of CFZ in rabbits because of enhanced lipophilicity and absorption. Finally, it was concluded that CFZ-PT appears useful as a prodrug of CFZ to improve the oral bioavailability of CFZ.

• Journal of Pharmaceutical Investigation
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• 제27권2호
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• pp.125-131
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• 1997

Ethoxycarbonyloxyethyl ester of ceftezole (CFZ-ET) was synthesized as a prodrug by esterification of ceftezole (CFZ) with ethoxycarbonyloxyethyl chloride and was confirmed by spectroscopic analyses. CFZ-ET was more lipophillic than CFZ as assessed by n-octanol and water partition coefficients at various pH. CFZ-ET itself did not show any microbiological activity in vitro, but showed substaintial microbiological activity after oral administration of CFZ-ET, indicating that CFZ-ET is converted to microbiologically active metabolite, probably CFZ, in the body. When CFZ-ET was incubated in blood, liver and intestine homogenates of rabbits, liver homogenate showed the fastest conversion of CFZ-ET. CFZ-ET appears rapidly metabolized in the liver when given orally due to the hydrolysis of the ester to CFZ, the parent drug of CFZ-ET. In vivo metabolism of CFZ-ET to CFZ was confirmed in rabbit by HPLC analysis. CFZ-ET were higher than those in the serum samples taken after oral administration of equivalent amount of CFZ. Oral bioavailability of CFZ-ET was 1.5-fold higher than that of CFZ in rabbits because of enhanced lipophilicity and absorption. Based on these findings, CFZ-ET appears useful as a prodrug of CFZ to improve the oral bioavailability of CFZ.

• 한국환경농학회지
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• 제31권4호
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• pp.293-299
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• 2012

본 연구에서는 화학비료와 퇴비를 과다하게 투입하여 인산의 집적 및 유출 위험성이 높은 양파-벼 재배지와 시설재배지의 인산 집적 특성과 인산가수분해효소를 이용한 집적 인산의 수계에서의 생물이용가능성을 평가하였다. 수용성 인산 중 많은 부분의 유기태 인산이 주변 수계에 유출될 위험성이 높았지만 그동안 제대로 평가되지 못했다. 본 연구결과에서 alkaline phosphomonoesterase와 phosphodiesterase에 의해 이모작토양에서 DUP의 12, 24%가 시설재배지 토양에서 DUP의 18과 44%가 분해되는 것으로 나타났다. 토양에 축적된 유기태 인산중 orthophosphate monoester와 diester가 주로 인산분해효소에 의해 분해되어 농경지 주변 수계로 유출시 생물 이용 가능성이 큰 것으로 평가되었다. 따라서 수계에서 인산의 거동을 이해할 때 유기태 인산에 대한 충분한 고려가 필요할 것이다.

• 한국식품저장유통학회지
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• 제23권5호
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• pp.753-757
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• 2016

본 연구에서는 도축장에서 폐수 처리되는 돈혈을 활용하여 단백질 분해 효소 처리를 하여 철분함량 및 용해도가 높은 철분분말을 제조하고자 하였다. 철분함량을 높이기 위하여 효소처리 및 혈액 분리 정도에 따른 돈혈 분말의 품질특성을 분석하였고, 그 결과 수급 받은 돈혈의 전혈에 Thermoase 0.2%를 첨가한 후 $60^{\circ}C$에서 4시간 처리하여 여과, 열풍건조처리를 하였을 때 철분함량이 110.00 mg/100 g 으로 가장 높은 것으로 확인되었으며, 재수화성 역시 높은 것을 확인하였다. 또 철분 보조제로써 활용 가능 여부를 확인하기 위하여 최종조건에 따라 제조 된 돈혈분말의 생체이용률을 측정하였으며, 대표적인 시중 판매 제품 보다 2.9배 높은 것으로 확인 되었다. 따라서 영양학적 가치가 있는 돈혈을 활용하여 철분분말을 제조한다면, 수입에 의존하고 있는 철분시장에 국내산 천연재료 공급이 가능할 뿐만 아니라 이의 폐기처리로 인한 비용처리 및 환경오염을 줄일 수 있을 것으로 기대된다.

• Journal of Pharmaceutical Investigation
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• 제23권2호
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• pp.61-69
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• 1993

Prodrug of cefazolin (CFZ) was prepared with the objective of improving its oral bioavailability. Cefazolin phthalidyl ester (CFZ-PT) was synthesized and evaluated as potential prodrug form. The successful synthesis of CFZ-PT was identified by spectroscopic analysis. Partition coefficient studies showed that CFZ-PT is more lipophilic than CFZ and the ester was hydrolyzed enzymatically into the parent drug in blood, liver and intestinal homogenates. The pharmacokinetic characteristics of CFZ-PT and CFZ were compared following oral administrations to rabbits. Serum CFZ concentration was determined by HPLC method and the ester compound (prodrug) was not detected in serum following oral administration of CFZ-PT. CFZ-PT did not have antimicrobial activity in vitro against Bacillus subtilis ATCC 6633, whereas CFZ-PT in serum after oral administration to rabbits had antimicrobial activity. From above observations, it was noted that CFZ-PT is rapidly hydrolyzed to CFZ in the body and the bioavailability of CFZ-PT was increased by 3.5-fold than that of CFZ. From these results of this study, it was concluded that CFZ-PT may be a novel prodrug of CFZ which can improve the oral absorption of CFZ.

• 한국지하수토양환경학회:학술대회논문집
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• 한국지하수토양환경학회 2000년도 추계학술대회
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• pp.196-201
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• 2000

The influence of adsorption on cadmium toxicity to soil microorganisms in smectite-rich soils and sediments was quantified as a function of solution and sorbent characteristics. Adsorption and surface complexation experiments were conducted to infer Cd sorption mechanisms to a reference smectite and three fractions of a Veritsol soil, and to elucidate the effects of the surface complexation on Cd bioavailability and toxicity in soils and sediments. Cadmium adsorption isotherms conformed to the Langmuir adsorption model, with adsorptive capacities of the different samples dependent on their characteristics. Equilibrium geochemical modeling (MINTEQA2) was used to predict the speciation of Cd in the soil suspensions using Langmuir and Triple Layer surface complexation models. The influence of adsorption and surface complexation on cadmium toxicity to soil microorganisms was assessed indirectly through the relative change in microbial hydrolysis of fluorescein diacetate (FDA) as a function of total Cd concentration and sorbent characteristics. Adsorption decreased the toxicity of Cd to soil microorganisms. Inner-sphere complexation is more effective than outer-sphere complexation in reducing the bioavailability and toxicity of heavy metals in soils and sediments.

• 약학회지
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• 제47권5호
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• pp.331-338
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• 2003

A butyrolactone ester of cefazolin (CFZ-BTL) was synthesized by the esterification of cefazolin (CFZ) with $\alpha$-bromo-${\gamma}$-butyrolactone. The synthesis was confirmed by the spectroscopic analysis. The CFZ-BTL was more lipophilic than the CFZ when assessed by n-octanol/water partition coefficients at various pH. The CFZ-BTL itself did not show any antimicrobial activity in vitro, but after oral administration of CFZ-BTL to rabbits, exerted significant anti-microbial activity in serum samples when measured by the inhibion zone method in nutrient agar plates, due to conversion of CFZ-BTL to an active metabolite, probably CFZ, in the body. The CFZ-BTL was also converted into CFZ as confirmed by in vitro incubation study, with tissue homogenates (liver, blood and intestine) of rabbits. The liver showed the fastest conversion rate, probably via the hydrolysis mechanism. In vivo metabolism of CFZ-BTL to CFZ was also confirmed in vivo serum samples by HPLC. The oral bioavailability of CFZ-BTL in rabbits was 1.6-fold increased when compared to CFZ, resulting from followed by enhanced lipophilicity increased passive absorption in the intestine.

• 약학회지
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• 제34권5호
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• pp.334-340
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• 1990

The bioequivalence of Mandol and Mancef (cefamondole nafate injection preparation) was investigated for 8 healthy human volunteers. Cefamandole nafate hydrolysis to cefamandole base in the blood and shows antibacterial activity. As the rate of the hydrolysis can be varied according to the buffer used in the preparation, the bioequivalence of cefamandole nafate I.V. was studied. A new HPLC method, the column switching technique, was developed and used for the simultaneous determination of cefamandole and cefamandole nafate in the plasma and in the urine. There were no statistically significant difference in between Mandol and Mancef for the parameters of AUC and Cp 0.25 hr even through the power of the test was not enough.

• Journal of Pharmaceutical Investigation
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• 제33권2호
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• pp.91-97
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• 2003

During the preparation of decoction from the mixture of Coptidis Rhizoma and Scutellariae Radix, insoluble copreciptate was formed. The coprecipitated product (COP) was composed of berberine and baicalin which was the active ingredient of Coptidis Rhizoma and Scutellariae Radix, respectively. COP was slightly soluble in water and could not be well absorbed after oral administration. This poor bioavailibility might be associated with its poor aqueous solubility. With the purpose of increasing the solubility and bioavailibility of COP, hydrolysis of COP by ${\beta}-glucuronidase$ was carried out. Hydrolyzed products (HOP) of COP were identified and assayed for active ingredients. The partition coefficient study, in situ absorption test, and pharmacokinetic study after oral administration were also performed. COP was found to be consisted of berberine and baicalin with molecular ratio of 1 to 1. This compound was hydrolyzed to berberine and baicalin by ${\beta}-glucuronidase$. The rate of hydrolysis was higher at higher temperature up to $50^{\circ}C$ and higher concentration of ${\beta}-glucuronidase$ up to 2500 unit under our experimental conditions. Baicalein, which is more liphophilic than baicalin, showed greater absorption in small intestine than baicalin did. The plasma concentrations of berberine and baicalein after oral administration of HOP were significantly higer than those of COP. The possible mechanism of increased bioavailibility of berberine and baicalein could be the hydrolysis of COP by ${\beta}-glucuronidase$. On the basis of the above results, it might be said that HOP should be a suitable preparation for increasing the bioavailibility of Coptidis Rhizoma and Scutellariae Radix.