• Biotechnology and Bioprocess Engineering:BBE
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• v.4 no.1
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• pp.32-35
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• 1999

Addition of ${\beta}$-cyclodextrin (${\beta}$-CD) polymer during the biotransformation of digitoxin into digoxin using cell suspension cultures of Digitalis lanata enhanced the conversion yield. Digitoxin showed better adsorption to CD polymer compared to digoxin, so that the optimization of addition time was found to be necessary. In the case of adding CD polymer 24 hours after the feeding of substrate digitoxin, the highest digoxin production could be achieved. At this period, digitoxin was almost consumed by cells and productivity was proportionally enhanced according as the amount of substrate was increased. Immobilization of CD polymer did not promote the biotransformation. When 3.33 g/L of CD selective inclusion complex formation could be expected. Adsorption rate was found to be rapid and saturation was obtained within 10 hours of contact.

• Archives of Pharmacal Research
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• v.24 no.5
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• pp.377-384
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• 2001

The reaction of either Digitoxin or Digoxin with cyanoacetic acid hydrazide gave the hydrazone derivatives 3a and 3b respectively. The reactivity of the latter products towards chemical reagents was studied to give heterocyclic derivatives with potential biological activities.

• KSBB Journal
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• v.13 no.4
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• pp.352-356
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• 1998

Addition of cyclodextrin in the biotransformation of digitoxin into digoxin by Digitalis lanata cell suspension cultures enhanced the conversion yield. Presence of cyclodextrin also supported good stability of the intermediate product, digoxin, for long time. Among several kinds of cyclodextrins, ${\beta}$-cyclodextrin provided the best results. It was found that the optimum form of cyclodextrin utilization was the external addition of iclusion complexes between digitoxin and ${\beta}$-cyclodextrin at 1: 2 molar ratio from the beginning of biotransformation. With the optimized conditions, addition of ${\beta}$-cyclodextrin enhanced the production of digoxin up to 1.55 fold. In this case, not only digitoxin consumption was increased, but also the production of by-product was reduced.

• 대한핵의학회:학술대회논문집
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• 1973.11a
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• pp.63.1-63.1
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• 1973

• 대한핵의학회:학술대회논문집
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• 1972.11a
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• pp.69.3-70
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• 1972

• 대한핵의학회:학술대회논문집
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• 1978.06a
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• pp.59.2-60
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• 1978

• Journal of Microbiology and Biotechnology
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• v.8 no.5
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• pp.478-483
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• 1998

For the enhanced production of a cardiac glycoside, digoxin, using in situ adsorption by biotransformation from digitoxin in plant cell suspension cultures, selection of proper resins was attempted and the culture conditions were optimized. Among various kinds of resins tested, Amberlite XAD-8 was found to be the best for digoxin production in considering adsorption characteristics as well as the effect on cell growth. Adequate time for resin addition was determined to be 36 h from the beginning of biotransformation and the presence of resins should be as short as possible to increase the productivity. In addition, to prevent the cells from direct contact with resin particles, immobilized systems were designed and examined. Immobilization further improved the advantages of in situ adsorption. It was confirmed that the increase of the contact area for mass transfer was an important factor in utilizing an immobilized system to enhance digoxin production.

• Proceedings of the Botanical Society of Korea Conference
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• 1995.06a
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• pp.79-90
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• 1995

Production of a cardiac glycoside, digoxin, by 12$\beta$-hydroxylation from digitoxin was studied in plant cell suspension cultures of Digitalis lanata. In order to increase the conversion yield, various culture conditions including immobilization were investigated and optimized. Since digoxin was released in the medium temporarily and converted further into a glucosylated product, deacetyllanatoside C, in situ adsorption of digoxin was employed to recover the product continuously. Amberlite resin XAD-8 showed the best adsorption characteristics for digoxin among the examined resins, and an integrated process was developed to increase the productivity. In addition, it was found that the utilization of $\beta$-cyclodextrin to entrap digoxin during the culture enhanced the biotransformation yield significantly.

• Microbiology and Biotechnology Letters
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• v.22 no.6
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• pp.651-658
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• 1994

For the production of digoxin by using biotransformation in suspension-cultured Digita- lis lanata cells, a two-stage culture process was optimized. Modified Murashige and Skoog medium was used for growth in the first stage and the cells were transferred to glucose solution for the production of digoxin from digitoxin via biotransformation in the second stage. When the cells were cultivated for 10 days in the growth period, 12$\beta$-hydroxylation capacity was the best. It was found that the optimum amount of digitoxin as substrate was 400 mg/l with initial cell density of 21%. Maximum productivity was achieved 5 days after transfer of cells to production medium. Sucrose and fructose provided similar digoxin yield as that in glucose, and 6% was proved to be the best glucose solution. Most of the components of modified MS medium except phosphate reduced the efficiency of digoxin formation. Besides, peptone and beef extracts inhibited 12$\beta$-hydroxylation, while promoting glucosylation. Finally, it was apparent that light enhanced the formation of digoxin significantly.

• 한국약용작물학회:학술대회논문집
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• 2007.11a
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• pp.317.2-317.2
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• 2007