Claims
- 1. A method for reducing leakage of loaded substance in the form of a solution, encapsulated in a closed vesicle, which method comprises dehydrating loaded micelle particles or loaded amphipathic micelle bilayers to form dehydrated micelle particles or dehydrated amphipathic micelle bilayers and then rehydrating said dehydrated micelle particles or amphipathic micelle bilayers by using a rehydration solution, wherein said rehydration is carried out in the presence of a saccharide in an outer aqueous phase of said closed vesicle at a temperature of about 20° C. or lower, and said closed vesicle before being rehydrated containing no internal saccharide therein, to reduce leakage of the loaded substance.
- 2. The method according to claim 1 wherein said saccharide is sucrose.
- 3. The method according to claim 1, wherein the temperature is in the range of from 0° C. to 10° C.
- 4. The method according to claim 1, wherein the closed vesicle is introduced with a pharmaceutically active substance or a diagnostic agent as the loaded substance.
- 5. The method according to claim 4, wherein the pharmaceutically active substance is an anti-tumor agent.
- 6. The method according to claim 5, wherein the anti-tumor agent is selected from the group consisting of adriamycin, daunomycin, vinblastine, a pharmaceutically acceptable salt thereof and derivatives thereof.
- 7. The method according to claim 6, wherein the pharmaceutically acceptable salt is formed together with a multivalent anionic substance.
- 8. The method according to claim 7, wherein the multivalent anionic substance is selected from the group consisting of citric acid, tartaric acid, and glutamic acid.
- 9. The method according to claim 1, wherein the closed vesicle is a liposome.
- 10. The method according to claim 9, wherein the liposome is obtained by lyophilizing or spray-drying a liposome in a liquid containing a saccharide.
- 11. The method according to claim 9, wherein the liposome is modified with an antibody and/or polyethylene glycol.
- 12. The method according to claim 1, wherein the rehydration solution has a pH within the neutral area.
- 13. The method according to claim 1, wherein the loaded substance is a water-soluble substance in an aqueous phase.
- 14. The method according to claim 1 wherein a saccharide is contained only in a liquid phase external to said micelle particles or amphipathic micelle bilayers during said dehydration.
- 15. The method according to claim 6 wherein the anti-tumor agent is adramycin.
Priority Claims (1)
Number |
Date |
Country |
Kind |
8-089277 |
Apr 1996 |
JP |
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Parent Case Info
This is a continuation of Ser. No. 08/843,640, filed Apr. 10, 1997, now abandoned.
US Referenced Citations (8)
Foreign Referenced Citations (3)
Number |
Date |
Country |
9106285 |
May 1991 |
WO |
9218104 |
Oct 1992 |
WO |
9704746 |
Feb 1997 |
WO |
Non-Patent Literature Citations (3)
Entry |
Madden et al., Biochimica et Bipophysica Acta, 817, pp. 67-74 (1985). |
Van Bommel et al., International Journal of Pharmaceutics, 22, pp. 299-310 (1984). |
Madden et al., Liposomes Rational Design, pp. 261-282 (1999). |
Continuations (1)
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Number |
Date |
Country |
Parent |
08/843640 |
Apr 1997 |
US |
Child |
09/897912 |
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US |