Artículos de revistas
Precipitation Of Clavulanic Acid From Fermentation Broth With Potassium 2-ethyl Hexanoate Salt
Registro en:
Separation And Purification Technology. , v. 66, n. 3, p. 598 - 605, 2009.
13835866
10.1016/j.seppur.2009.01.010
2-s2.0-64449083755
Autor
Hirata D.B.
Oliveira J.H.H.L.
Leao K.V.
Rodrigues M.I.
Ferreira A.G.
Giulietti M.
Barboza M.
Hokka C.O.
Institución
Resumen
This paper describes a direct precipitation reaction of clavulanic acid (CA) using potassium 2-ethyl hexanoate salt. Clavulanic acid is an important molecule produced by the pharmaceutical industry to overcome problems relating to bacterial resistance to antibiotics. However, precipitation of this organic compound has been little studied and, unlike inorganic compounds, its isolation and precipitation usually involve a complex and meticulous process. The purpose of this work was to improve the purification process and increase the yield of CA from fermented broth by examining the influence of the combined concentrations of clavulanic acid (in organic solvent) and potassium 2-ethyl hexanoate on the potassium clavulanate precipitation reaction. Clavulanic acid was extracted at temperatures below 20 °C and preferably close to 15 °C in the water-immiscible organic solvent ethyl acetate. The drying step was performed with a suitable desiccant to produce an insoluble salt of potassium clavulanate. The resulting precipitate was crystalline and stable, a finding that was confirmed by an NMR 1H analysis. © 2009 Elsevier B.V. All rights reserved. 66 3 598 605 Brown, A.G., Butterworth, D., Cole, M., Hanscomb, G., Hood, J.D., Reading, C., Rolinson, G.N., (1976) J. Antib., 6, pp. 668-669. , Comunications to the editor. V. XXIX Baggaley, K.H., Brown, A.G., Schofield, C.J., (1977) Nat. Prod. Rep., 14, p. 309 Mayer, A.F., Anspach, F.B., Deckwer, W.D., (1996) Biosep, 6, p. 25 Mayer, A.F., Hartmann, R., Decker, W.D., (1997) Eng. Sci., 52 (24), p. 4561 Barboza, M., Almeida, R.M.R.G., Hokka, C.O., (2002) Biosep, 10, p. 221 Barboza, M., Almeida, R.M.R.G., Hokka, C.O., (2002) Ind. Eng. Chem. Res., 41 (23), p. 5789 Barboza, M., Almeida, R.M.R.G., Hokka, C.O., (2003) Biochem. Eng. J., 14, p. 19 Capuder, E., (1988), US Patent 5780274Gullo, V.P., McAlpine, J., Lam, K.S., Baker, D., Peterson, F.J., Drug discovery from natural products (2006) J. Microb. Biotechnol., 33, pp. 523-531 Cardoso, J.P., Process for the isolation of a pharmaceutically acceptable alkali metal salt of clavulanic acid (1998), WO Patent 42858Capuder, E., US 6180782B1 2001E. Capuder, US 2001/0007761A1 (2001)Cole, M., Howarth, T.T., Reading, C., (1985) US 4525353 Kim, J.W., Choi, N.H., Choi, G.S., Lee, D.W., (1995), WO Patent 34194Teodoro, J.C., Baptista-Neto, A., Cruz-Hernandez, I.L., Hokka, C.O., Badino, A.C., (2005) App. Microb. Biotechnol., 72, p. 450 Ortiz, S.C.A., Hokka, C.O., Badino, A.C., (2007) Enz. Microb. Technol., 40, p. 1071 Foulstone, M., Reading, C., (1982) Antimic Ag. Chemoth., 22 (5), p. 753 Bersanetti, P.A., Almeida, M.R.G., Pasotto, M.B., Araujo, M.L.G.C., Hokka, C.O., Kinetic studies on clavulanic acid degradation (2005) Biochem. Eng. J., 23, pp. 31-36 Mullin, J.W., (1993) Crystallization. 3rd ed., , Butterworth-Heinemann Ltd., London p. 527