• Biotechnology and Bioprocess Engineering:BBE
• /
• 제11권3호
• /
• pp.211-214
• /
• 2006

Immobilized Candida antarctica lipase was used to catalyze the separation of ketoprofen into its components by means of esterification followed by the enzymatic hydrolysis of the ester product. In this study, ketoprofen underwent esterification to ethanol in the presence of isooctane. When the reaction was complete, 58.3% of the ketoprofen had been transformed into an ester. The ketoprofen remaining in solution after the reaction was complete consisted primarily of its S-enantiomer (83.0%), while the 59.4% of the ketoprofen component of the ester consisted of its R-enantiomer. We then subjected the ester product to enzymatic hydrolysis in the presence of the same enzyme and produced a ketoprofen product rich in the R-enantiomer; 77% of this product consisted of the R-enantiomer when 50% of the ester had been hydrolyzed, and 90% of it consisted of the R-enantiomer when 30% of the ester had been hydrolyzed. By contrast, the R-enantiomer levels only reached approximately 42 and 65%, respectively, when 50 and 30% of the racemic ester was hydrolyzed under the same conditions.

• Biotechnology and Bioprocess Engineering:BBE
• /
• 제9권4호
• /
• pp.285-291
• /
• 2004

A simulated moving bed (SMB) chromatography system is a powerful tool for preparative scale separation, which can be applied to the separation of chiral compound. We have de-signed our own lab-scale SMB chromatography using 5 HPLC pumps, 6 stainless steel columns and 4 multi-position valves, to separate a racemic mixture of ketoprofen in to its enantiomers. Our design has the characteristics of the low cost for assembly for the SMB chromatography and easy repair of the unit, which differs from the designs suggested by other investigators. It is possible for the flow path through each column to be independently changed by computer control, using 4 multi-position rotary valves and 5 HPLC solvent delivery pumps. In order to prove the operability of our SMB system, attempts were made to separate the (S)-ketoprofen enantiomer from a ketoprofen racemic mixture. The operating parameters of the SMB chromatography were calculated for ketoprofen separation from a batch chromatography experiment as well as by the triangle theory. With a feed concentration of 1 mg/mL, (S)-ketoprofen was obtained with a purity of 96% under the calculated operating conditions.

• 한국생물공학회:학술대회논문집
• /
• 한국생물공학회 2001년도 추계학술발표대회
• /
• pp.693-696
• /
• 2001

Ketoprofen racemate를 각 enantiomer로 분리하고자 이동상의 조성을 변화하여 실험을 수행한 결과, hexane과 t-BME의 비가 60/40(%v/v)인 경우 적합한 체류시간과 분리도를 얻을 수 있었으며, 이동상의 acetic aicd를 0.1%(v/v) 첨가한 경우 낮은 pH에서 분리가 효율적으로 일어났다. 또한, 시료의 농도를 변화시켜 실험을 수행한 경우, 2000ppm까지는 선택도에 큰 변화없이 분리를 수행할 수 있었으나, 농도가 1000ppm 이상인 경우 분리도가 1.00미만으로 낮은 값을 보였다.

• Biotechnology and Bioprocess Engineering:BBE
• /
• 제10권4호
• /
• pp.341-345
• /
• 2005

Since it is troublesome to estimate adequate flow rates in four sections of SMB chromatography, a systematic determination of the flow rates has been suggested by using ketoprofen as a model chiral enantiomer. S-ketoprofen. less retained species, was separated from raffinate stream and the variation in its purity was dependent on the changes of the flow rate of section 4 ($Q_4$), the raffinate flow rate ($Q_{raf}$), and the feed flow rate ($Q_{feed}$) under a fixed switch­ing time t$^{\ast}$. When one parameter was changed at the given experimental condition, purities of product were changed and these phenomena has be well explained by the triangle theory.

• KSBB Journal
• /
• 제14권2호
• /
• pp.225-229
• /
• 1999

본 연구에서는 광학적으로 순수한 S-(+)-ketoprofen을 얻기 위한 효소적 분할공정을 개발하는 것을 그 내용으로 하고 있다. 결과에 의하면 Candida rugosa 유래의 lipase는 음이온 교환수지에 의해 두 가지 형태의 효소로 분리되었으며 특히 첫 번째 peak의 lipaserk (S)-enantiomer에 대해 선택성이 매우 높은 것으로 나타났다. 온도 pH, 첨가제의 영향에 대해서 조사한 결과 높은 활성을 유지하면서 광학적으로 순수한 (S)-ketoprofen을 얻는 조건을 찾지는 못하였으나, $37^{\circ}C$의 온도에서 선택성이 높았으며 ethylen glyco과 같은 polyalcohol 종류가 첨가될 경우 선택성이 증가한다는 결과를 얻을 수 있었다.

• 한국생물공학회:학술대회논문집
• /
• 한국생물공학회 2001년도 추계학술발표대회
• /
• pp.625-628
• /
• 2001

토양으로부터 특이적인 광학 이성질체에 활성을 갖는 두 효소원을 선별한 후, 동정하여 Pseudomonas sp. S34와 B. stearothermophilus JY144로 명명하였고, genecloning과 sequencing을 통해 유전자의 특성 및 관련효소들과의 유연관계를 규명하였다. 규명된 정보의 분석과 비교를 통해 ketoprofen ethyl ester에 활성을 갖는 효소들의 구조적 특성을 추론할 수 있었고, 이를 바탕으로 발현시스템을 구축하였다. 대량생산된 효소를 활용한 반응의 결과 높은 수율과 순도를 갖는 각각의 광학이성질체를 경제적으로 생산할 수 있었다.

• 한국생물공학회:학술대회논문집
• /
• 한국생물공학회 2002년도 생물공학의 동향 (X)
• /
• pp.489-492
• /
• 2002

We have performed batch chromatography experiments to calculate parameters which are used to design SMB chromatography system. Isotherms of S- and R-ketoprofen enantiomers were gained from small amount loading experiments in a column, and flow rate of four zones of SMB chromatography were calculated using mass balance equations. As a results, diameter and length of columns were 10mm and 600mm, and flow rate of each zone were as follows; $Q_{Feed}$=1.00ml/min ,$Q_{Elu}$=2.81ml/min ,$Q_{Raf}$=1.81ml/min ,$Q_{Ext}$=2.00ml/min , and $Q_{Rec}^{TMB}$=10.75ml/min , From the Darcy's equation, the pressure drop in whole columns of SMB chromatography was 128bar.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
• /
• pp.215.1-215.1
• /
• 2003

A various ${\alpha}$-arylmethylpropionic acids(profen) have been widely used as non-steroidal anti-inflammatory drugs for the relief of acute and chronic rheumatoid arthritis and osteoarthritis, as well as for other connective tissue disorders and pains. Example is fenoprofen, ibuprofen, ketoprofen, and naproxen. All are chiral and, except for naproxen and ibuprofen, are marketed in racemic form. Enantioseparations of profens have been of considerable interest becaus their anti-inflammatory and analgesic effects have been attirbuted almost exclusively to their (S)-enantiomer. (omitted)

• 한국생물공학회:학술대회논문집
• /
• 한국생물공학회 2003년도 생물공학의 동향(XII)
• /
• pp.506-510
• /
• 2003

TMB 크로마토그래피의 물질수지식으로부터 SMB 크로마토그래피의 디자인 파라미터들을 계산할 수 있으며, 이를 이용하여 6 칼럼 SMB 크로마토그래피 장치를 디자인하였다. SMB 크로마토그래피 장치는 4개의 multi position rotary valve를 사용하여 연속적으로 각 칼럼으로의 유로를 제어할 수 있으며, 효율적인 SMB 크로마토그래피 장치를 구현할 수 있다. 또한 회분식 실험으로부터 얻어진 $m_2$, $m_3$ diagram으로부터 SMB 크로마토그래피의 조작에 필요한 파라미터들을 계산할 수 있었다.