• Journal of Veterinary Clinics
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• v.16 no.1
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• pp.193-198
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• 1999

Ketoprofen has been used as nonsteroidal anti-inflammatory (NSAI) agent for analgesia in surgical patients and increasing numbers of surgical patients are chronically take some forms of NSAI drugs. The purpose of this study was to investigate the therapeutic effects of ketoprofen on the healing of a closed linear surgical wound and on the contraction of an opened surgical wound in rats. The experimental groups were divided into two groups and ten rats were allocated in each group. In ketoprofen-treated group, the rats were given 2.5 mg/mg/day of ketoprofen by s.c. for ten days. In control group, the rats were given 1ml of benzyl alcohol and distilled water by s.c. for ten days. After time period, all rats were sacrificed, and the breaking strength and the collagen concentrations, at the wound site, were measured. In ketoprofen-treated group, the mean breaking strength and the mean collagen concentration were significantly decreased when compared with those of controls. The ketoprofen-treated group had shown a mean rate of wound contraction less than that of the control, although not statistically significant. These results suggested that ketoprofen impaired wound healing.

• Korean Chemical Engineering Research
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• v.47 no.1
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• pp.54-58
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• 2009

Ketoprofen and ibuprofen are non-steroid anti-inflammatory drug(NSAID) that have analgesic and antipyretic properties. (S)-ketoprofen and (S)-ibuprofen have pharmacological activity, while (R)-ketoprofen and (R)-ibuprofen are either inactive or have side effect. The chiral separation of racemic ketoprofen and ibuprofen enantiomers was carried out by using a Kromasil HPLC column. Some chromatographic parameters (selectivity, resolution, number of theoretical plates and ${\Delta}H$) are calculated under different mobile phase compositions of hexane/t-BME/acetic acid and temperatures. The selectivity, resolution and number of theoretical plates were observed high at $25^{\circ}C$ and the composition of hexane/t-BME/acetic acid (80/20/0.1).

• KSBB Journal
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• v.14 no.2
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• pp.225-229
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• 1999

Enzymatic resolution reactions were investigated using Candida rugosa lipase for the production of potically pure S-(+)-Ketoprofen. When the enzymatic hydroysis (and esterification) of recemic ketoprofen esters (and recemic ketoprofen with alcohol) was investigated comparatively, aqueous media was more specific for S-enantiomer than organic media. In the enzymatic hydrolysis of racemic ketoprofen ethyl ester in aqueous media, optimal temperature and pH for enantioselectivity were $37^{\circ}C$ and 4, respectively. The stereoselectivity of the enzyme was enhanced by adding dialcohols such as ethylene glycol and propylene glycol. The enantiomeric ratio obtained in the 40 %(v/v) ethylene glycol was 2-fold higher than that without the additive. By adding $CH_2Cl_2$, $CHCl_3$ and $CCl_4$ (5%,v/v), the enantioselectivity was reversed. A dramatic increase in the stereoselectivity was achieved using lipase purified by anion exchange chromatography. The type A lipase(the first eluted lipase fraction) showed an enantiomeric ratio of >100, whereas the type B lipase(the second eluted lipase fraction) exhibited enantimomer ratio of 9.0 in the hydrolysis of racemic ketoprofen ethyl ester.

• Journal of Pharmaceutical Investigation
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• v.21 no.1
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• pp.1-10
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• 1991

Hydrogels containing ketoprofen were prepared by adding NaOH or $Ca(OH)_2$ solution to Eudragit L, S and Eudispert hv at various concentration. And xerogels were prepared by drying hydrogels. On the other hand, organogels containing ketoprofen were prepared by mixing Eudragit L or S and propylene glycol. Effects of polymer content and base on drug release were investigated using KP V dissolution method. The release rate of ketoprofen from Eudragit L & S hydrogel decreased with increasing in polymer content. And the drug release rate from cal. hydroxide based gels were more decreased than that from sod. hydroxide based gels. At pH 7.2 dissolution medium, e release of ketoprofen from Edispert hv hydrogel followed apparent zero order kinetics. The release of ketoprofen from xerogel involved in simultaneous absorption of water and desorption of ketoprofen via a pH-dependant swelling controlled mechanism. The release of ketoprofen from Eudragit S organogels followed apparent zero order kinetics, providing strong evidence for a surface erosion mechanism.

• Journal of Veterinary Clinics
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• v.23 no.4
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• pp.400-404
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• 2006

This study demonstrates the anti-arthritic effect of topical application of ketoprofen gel containing N-methyl-2-pyrrolidone (NMP) in adjuvant arthritis therapy. Adjuvant arthritis was induced by a single injection of Freund's complete adjuvant (FCA). Mature female Sprague-Dawley rats were designated to 3 groups such as control group, K10 group (ketoprofen 10 mg/rat), and NK10 group (ketoprofen 10 mg/rat containing NMP). The anti-arthritic activity of ketoprofen containing NMP was tested not only as to its capability to suppress the inflammatory edema, but also bone damage (X-ray score and regional bone uptake) of the hind paw in arthritis-induced rats. These results showed a higher efficacy of ketoprofen containing NMP than ketoprofen treatment in the adjuvant-induced arthritis. Ketoprofen containing NMP has good intrinsic characteristics for formulation in an efficacious anti-inflammatory topical application.

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.693-696
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• 2001

Ketoprofen racemate is very useful pharmaceutical intermediate, but the hardness of separation to each enantiomer is most a barrier to apply pharmaceutical industry. To overcome this difficulty, we would like to separate S-ketoprofen from ketoprofen racemate. To design suitable mobile phase, hexane and t-BME(tri-buthyl-methyle-ether) were used to elute peaks of ketoprofen racemate separately. When the ratio of hexane/t-BME/acetic acid was 60/40/0.1(%v/v), each component was separated successfully. In order to separate large amount of S-ketoprofen, sample concentration was increased from 100ppm to 2000ppm. In this case, resolution was decreased due to the overlapping of peaks(1.65${\rightarrow}$0.94).

• KSBB Journal
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• v.29 no.4
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• pp.250-262
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• 2014

A simulation study for finding purity changes of extract and raffinate as well as the best purity of (S)-ketoprofen in simulated moving bed (SMB) was performed with changing parameters of $m_2$ and $m_3$ from triangle theory. Aspen simulator allowed separation process simulation of (R)- and (S)-ketoprofen in SMB and compared 4-bed SMB and 8-bed SMB based on the same Henry constant and mass transfer coefficient. The 4-bed SMB consisted of 4 columns (200 mm of length, 10 mm of diameter) and the 8-bed SMB constructed by 8 columns (100 mm of length, 10 mm of diameter), and therefore total column length was made the same as 800 mm. Considering purities of both (R)-and (S)-ketoprofen, both 4-bed SMB and 8-bed SMB had the best purity when $m_2$ and $m_3$ were on 12.0 and 13.0 in the center of triangle. Taking only (S)-ketoprofen into account, 4-bed SMB as well as 8-bed SMB had the best purity when $m_2$ and $m_3$ were on 10.9 and 12.6 in the left outside triangle, and their purities were 93.3 % for 4-bed SMB and 96.9 % for 8-bed SMB.

• Biotechnology and Bioprocess Engineering:BBE
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• v.9 no.4
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• pp.285-291
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• 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.

• Biotechnology and Bioprocess Engineering:BBE
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• v.11 no.3
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• pp.211-214
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• 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.

• Archives of Pharmacal Research
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• v.27 no.12
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• pp.1295-1301
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• 2004

The enantiomeric composition tests on flurbiprofen and ketoprofen present in patch products and in urine excretions following patch applications were performed as diastereomeric (R)-(+)- 1-phenylethylamides by achiral gas chromatography and by gas chromatography-mass spectrometry in selected ion monitoring mode. The method for determination of (R)- and (S)-enantiomers in the range from 0.1 to 5.0 ${\mu}$g was linear (r ${\ge}$ 0.9996) with acceptable precision (% RSD ${\le}$5.2) and accuracy (% RE = 0.6 ~ -2.4). The enantiomeric compositions of flurbiprofen in one patch product and of ketoprofen in five different products were identified to be racemic with relatively good precision (${\le}$ 6.4%). The urinary excretion level of (R)-flurbiprofen was two times higher than its antipode, while the comparable excretion levels of (R)- and (S)-enantiomers for ketoprofen were observed.