Method of manufacturing pharmaceutical preparations containing liposomes

1. A method of manufacturing a liposome-containing preparation comprising mixing a supercritical carbon dioxide, one or more liposome membrane constituents including a phospholipid exhibiting a phase transition temperature and a water-soluble chemical, and the method comprises the steps of:

(a) mixing one or more liposome membrane constituents and liquefied carbon dioxide in a pressure vessel,

(b) increasing a pressure within the vessel with heating at a temperature of 32 to 55° C. to bring the carbon dioxide to a supercritical state,

(c) supplying an aqueous solution of the water-soluble chemical to a mixture of the liposome membrane constituent and the supercritical carbon dioxide with stirring to form a mixed solution, and

(d) decreasing the pressure within the vessel to discharge the carbon dioxide from the mixed solution to form an aqueous dispersion of liposomes enclosing the water-soluble chemical

wherein the liposome membrane constituents include a compound containing a polyethylene glycol group, and in step (c), stirring is subjected to strong agitation satisfying the following requirement:

C=N×V −0.15

wherein C is a number of revolutions per minute (rpm), V is a volume (L) of a mixed solution and N is 300 to 3000.

2. The method of claim 1 , wherein the phase transition temperature of the phospholipid is within the range of 22 to 60° C.

3. The method of claim 1 , wherein the phospholipid exhibiting a phase transition temperature is at least one selected from the group of hydrogenated soybean lecithin, hydrogenated phosphatidylcholine and distearoylphosphatidylcholine.

4. The method of claim 1 , wherein the phospholipid exhibiting a phase transition temperature is dimyristoylphosphatidylcholine or dipalmitoylphosphatidylcholine.

5. The method of claim 1 , wherein the water-soluble chemical is a contrast medium compound or an anticancer compound.

6. The method of claim 5 , wherein, the water soluble compound is the contrast medium compound which is a water-soluble iodine compound.

7. The method of claim 1 , wherein in step (b), the temperature is 32 to 50° C.

8. The method of claim 1 , wherein in step (c), the stirring is subjected to strong agitation at a rate of 400 to 4,000 rpm.

9. The method of claim 1 , wherein the method further comprises (e) subjecting the aqueous dispersion of liposomes to filtration using a membrane filter having a pore size of 0.1 to 1.0 μm.

10. The method of claim 1 , wherein the compound containing a polyethylene glycol group is a phospholipid containing a polyethylene glycol group or a cholesterol containing a polyethylene glycol group.

11. The method of claim 1 , wherein a weight ratio of chemical included in vesicles to lipid forming vesicular membrane is 1 to 8.