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The Korean Society for Biotechnology and Bioengineering (한국생물공학회)
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Preparation of Water-Soluble Solid Forms Containing Ursolic Acid Using Supercritical Fluid

초임계유체를 이용한 우르솔산 함유 고체 가용화 제제의 제조

  • Lee, Sang-Yun (Department of Chemical and Biochemical Engineering, The University of Suwon) ;
  • Jung, Ju-Hee (Department of Chemical and Biochemical Engineering, The University of Suwon) ;
  • Jung, In-Il (Department of Chemical and Biochemical Engineering, The University of Suwon) ;
  • Choi, Moon-Jae (Nebion Co., Ltd.) ;
  • Park, Eui-Hoon (Nebion Co., Ltd.) ;
  • Ryu, Jong-Hoon (Department of Chemical and Biochemical Engineering, The University of Suwon) ;
  • Lim, Gio-Bin (Department of Chemical and Biochemical Engineering, The University of Suwon)
  • 이상윤 (수원대학교 공과대학 화공생명공학과) ;
  • 정주희 (수원대학교 공과대학 화공생명공학과) ;
  • 정인일 (수원대학교 공과대학 화공생명공학과) ;
  • 최문재 (네비온(주)) ;
  • 박의훈 (네비온(주)) ;
  • 유종훈 (수원대학교 공과대학 화공생명공학과) ;
  • 임교빈 (수원대학교 공과대학 화공생명공학과)
  • Published : 2007.10.30
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Abstract

In this work ursolic acid (UA), a poorly water-soluble compound, was inclusion complexed with 2-hydroxypropyl-$\beta$-cyclodextrin (HP-$\beta$-CD) by various methods such as kneading, solvent evaporation and two types of supercritical fluid processes. The solubility and characteristics of these UA/HP-$\beta$-CD complexes were investigated by scanning electron microscopy, x-ray diffraction and HPLC. The water solubilities of the two complexes obtained from solvent evaporation and ASES processes were observed to increase up to 6$\sim$240 folds and 12$\sim$56 folds, respectively, compared with that of unprocessed UA. The stability of UA/HP-$\beta$-CD complex samples in cosmetic formulations was examined at various temperatures for one month. The UA/HP-$\beta$-CD complex prepared by solvent evaporation was found to be most stable among all the cosmetic formulations tested in our experiments.

본 연구에서는 뛰어난 주름개선효능을 가지고 있지만 수용액상에서의 낮은 용해도로 인해 사용에 제약이 있는 UA의 용해도를 향상시키기 위하여 HP-$\beta$-CD와의 포접체를 형성하는 UA함유 제제를 제조하고자 하였으며 특히 초임계유체 공정기술을 포접화합물 제조에 도입하여 초임계 기술의 적용의 가능성을 조사하였다. UA의 용해도를 증가시키기 위한 제조방법으로 HP-$\beta$-CD와의 혼합물을 반죽법, 용매증발법 및 초임계유체공정을 이용하여 제조하고, 각 제조시료들의 용해도 증가 및 특성을 확인한 결과 용매증발법과 초임계 ASES공정에 의해 물에 대한 용해도가 증가된 UA/HP-$\beta$-CD 제제를 얻을 수 있었다. 각 방법에 의해 제조된 UA 함유 제제의 화장품 제형에서의 안정도 실험을 수행하였으며 실험결과 유화제형에서는 모든 제제가 시간 및 온도에 대한 안정성을 보였으나 가용화제형에서는 ASES 제제와 Ursolisome 제제의 경우 시간이 경과하거나 함유 UA농도가 증가함에 따라 화장품 제형의 현탁도가 증가함을 확인할 수 있었다.

Keywords

References

  1. Tokuda, H., Ohigashi, H., Koshimizu, K., and Y. Ito (1986), Cancer Lett. 33, 279-285 https://doi.org/10.1016/0304-3835(86)90067-4
  2. Ohigashi, H., Takamura, H., Koshimizu, K., Tokuda, H., and Y. Ito (1986), Cancer Lett. 30, 143-151 https://doi.org/10.1016/0304-3835(86)90082-0
  3. Huang, M. T., Ho, C. T., Wang, Z. Y., Ferraro, T., Lou, Y. R., Stauber, K., Ma, W., Georgiadis, C., Laskin, J. D., and A. H. Conney (1994), Cancer Res. 54, 701-708
  4. Sohn, K. H., Lee, H. Y., Chung, H. Y., Young, H. S., Yi, S. Y. and K. W. Kim (1995), Cancer Lett. 94, 213-218 https://doi.org/10.1016/0304-3835(95)03856-R
  5. Jie Liu (2005), Oleanolic acid and ursolic acid: Research perspectives, J. Ethnophamacology 100, 92-94 https://doi.org/10.1016/j.jep.2005.05.024
  6. Badawy, S. I. F., M. M., Ghorab, and C. M., Adeyeye (1996), Characterization and bioavailability of danazol-hydroxypropyl $\beta$-cyclodextrin coprecipitates, Int. J. Pharm. 128, 45-54 https://doi.org/10.1016/0378-5173(95)04214-8
  7. Badawy, S. I. F., A. L. Marshall, M. M. Ghorab, and C. M. Adeyeye (1996), A study of the complexation between danazol and hydrophilic cyclodextrin derivatives, Drug Dev. Ind. Pharm. 22, 959-966 https://doi.org/10.3109/03639049609065926
  8. Badawy, S. I. F., M. M. Ghorab, and C. M. Adeyeye (1996), Bioavailability of danazol-hydroxypropyl-$\beta$-cyclodextrin complex by different routes of administration, Int. J. Pharm. 145, 137-143 https://doi.org/10.1016/S0378-5173(96)04763-1
  9. Soppimath, K. S., Aminabhavi, T. M., Kulkarni, A. R, and W. E. Rudzinski (2001), Biodegradable polymeric nanoparticles as drug delivery devices, J. Control Release 70, 1-20 https://doi.org/10.1016/S0168-3659(00)00339-4
  10. Siempmann, J. and N. A. Peppas (2001), Modelling of drug release from delivery systems based on hydroxypropyl mcthylccllulose, Adv. Drug Del. Rev. 48, 139-157 https://doi.org/10.1016/S0169-409X(01)00112-0
  11. Chattopadhyay, P. and R B. Gupta (2002), Supercritical CO_2, based production of magnetically responsive micro- and nanoparticles for drug targeting, Ind. Eng. Chem. Res. 41, 6049-6058 https://doi.org/10.1021/ie020205b
  12. De Gioannis, B., Patrick, J., and P. Subra (2004), Morphology and growth control of griseofulvin recrystallised by compressed carbon dioxide as antisolvent, J. Crystal. Growth 262, 519-526 https://doi.org/10.1016/j.jcrysgro.2003.10.025
  13. Jung J. and M. Perrut (2001), Particle design using supercritical fluids: literature and patent survey, J. Supercrit: Fluids 20, 179-219 https://doi.org/10.1016/S0896-8446(01)00064-X
  14. Foster, N., R, Dehghani, F., Bustami, R. T., and H. K. Chan (2003), Generation of lysozyme-lactose powders using the ASES process, In: Proc 6th Int. Symp Supercrit, Fluid 3, 1831-1836
  15. Foster, N. R, Meure, L. A., Barrett, A. M., Abbasi, F., and F. Dehghani (2003), Micronisation of griseofulvin by the aerosol solvent extraction system, In: Proc 6th Int. Symp. Supercrit, Fluid 3, 1771-1776
  16. Foster, N. R, Ng, A. S., Dehghani, F., and H. L. Regtop (2003), Micronisation of tobramycin using dense gas anti-solvent techniques, In: Proc. 6th Int. Symp. Supercrit, Fluid 3, 1647-1652
  17. Lee, Y. W., Lee, j. W., and J. S. Lim (2003), The formation of aspirin micro particulate using supercritical $CO_2,$ as solvent and antisolvent, In: Proc 6th Int. Symp. Supercrit, Fluid 3, 1777-1782
  18. Charoenchaitrakool, M., F. Dehghani, and N. R Foster (2002), Utilization of supercritical carbon dioxide for complex formation of ibuprofen and methyl-$\beta$-cyclodextrin, Int. J. Pharm. 239, 103-112 https://doi.org/10.1016/S0378-5173(02)00078-9
  19. Mingqua G., et al. (2003), Studies on the non-covalent complexes between oleanolic acid and cyclodextrins using electrospray ionization tandem mass spectrometry, J. Mass Spectrom. 38, 723-731 https://doi.org/10.1002/jms.486
  20. Suzuki, et al. (1994), Water-soluble pentacyclic triterpene composition and method for producing the same, US Patent, 5314877