Extemporaneous preparation type kit of a pharmaceutical substanc

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...

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514669, 514762, 514943, A61K 3120, A61K 3113, A61K 3101

Patent

active

052294226

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE ART

The present invention relates to an extemporaneous preparation type kit of pharmaceutical substance-containing fat emulsion. More particularly, the present invention relates to an extemporaneous preparation type kit, which is composed of (I) a fat emulsion and (II) a pharmaceutical substance composition and capable of giving a pharmaceutical substance-containing fat emulsion having the pharmaceutical substance embedded in the fat emulsion particles by mixing (I) the fat emulsion with (II) (a) a pharmaceutical substance composition containing a pharmaceutical substance and a solvent or (b) a pharmaceutical substance composition containing a pharmaceutical substance and an excipient, and to a method of preparation of the pharmaceutical substance-containing fat emulsion.


BACKGROUND OF THE ART

Fat emulsion is a kind of emulsion having very fine particles of fat homogeneously dispersed in water. Especially, an intravenous fat emulsion has been developed for supplying calories to the patients who cannot take them orally and is now commercially available [cf. "the fundamentals and preparation of high-calorie transfusion solution": second press; p. 74-81, (1981); Sigehiko Shimada, YAKUJI NIPPO (Japan)]. Usually, fat emulsion means such intravenous emulsions.
This type of fat emulsion is normally prepared by heating the fat component such as soybean, cotton seed or safflower oil along with an emulsifier such as yolk phospholipid, lecithin or soybean lecithin, and other additives, roughly emulsifying them together with a needed amount of water by means of a homomixer, then finely emulsifying using a jet-type high-pressure homogenizer, and sterilizing with high-pressure steam.
The fat emulsion thus prepared is a homogeneous dispersion of oil-drop particles (of less than 1 micrometer average particle size) coated with an emulsifier on their surface in water. The oil-drop particles coated with an emulsifier on their surface is defined as "fat emulsion particles" here.
In recent years, a variety of trials have been made to develop more reasonable pharmacotherapy with increased efficacy and safety of medicinal substances by controlling the release of the substance from the preparation, preventing the substance from being inactivated in vivo, controlling the distribution of the substance in the living body, or prolonging the retention at the affected part. One of these trials is to develop a satisfactory carrier in which the pharmaceutical substance in the preparation is embedded. In this method, the behavior or efficacy of the pharmaceutical substance largely depend on the absorption, distribution, metabolism, and excretion of the carrier in vivo, differing from a usual preparation in which the pharmaceutical substance is released from the preparation, absorbed, distributed, metabolized and excreted alone in vivo.
The meaning of "a pharmaceutical substance is embedded in a carrier" is defined as follows:
A part or all of the molecules of the pharmaceutical substance constituting the preparation along with the carrier and others such as an excipinet are individually included in the carrier partially or entirely in their molecular bodies.
One of the examples of the entire part of one molecule of the pharmaceutical substance embedded in the carrier is the case in which the pharmaceutical substance is dissolved in the carrier, while an example of one molecule partially included is the case where a part of the molecule exists in the carrier and the rest is exposed to the outside.
Liposome of doubled lipid membrane has been known as such a carrier for a pharmaceutical substance.
Recently, however, trials of utilizing the above-stated fat emulsion particles as a carrier for embedding the pharmaceutical substance have been reported. They describe that the pharmaceutical substance-containing fat emulsion prepared by emulsifying the pharmaceutical substance along with fat and emulsifier prolonged the half-life in vivo of the substance compared with the case where the substance was given without the fat emulsio

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Fortner et al, Am. J. Hosp. Pharm., 32:582-584 (1975).
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Chemical Abstracts, 101:375 (1984) Huang, L et al.
Physicians Desk Reference (Ed: Carrie. Henwood) pub. by Edward Barnhart (1990) 44th Edition pp. 502-2455.

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