Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1995-10-23
2000-02-01
Carr, Deborah
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514476, 514599, 514602, A61K 3170
Patent
active
06020317&
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to compounds of the following general formula [I]. ##STR1## wherein R.sup.1 and R.sup.2 are not the same and each represents OY or --A--(CH.sub.2)n-E. n represents a whole number of 0-4. E represents pyrrolidino, piperidino, substituted or unsubstituted piperazino, morpholino, substituted or unsubstituted guanidino, or ##STR2## (where R.sup.3 and R.sup.4 are the same or different and each represents hydrogen, lower(C.sub.1-4)alkyl, hydroxy-lower(C.sub.1-4)alkyl, or mono- or di- (lower)alkylamino-alkyl(C.sub.2-6)).
A represents the following 1, 2, 3, 4, 5, 6, or 7. ##STR3##
R and Y are the same or different and each represents a saturated or unsaturated aliphatic hydrocarbon group of 10-30 carbon atoms or a saturated or unsaturated fatty acid residue of 10-30 carbon atoms.
The compound according to the present invention (hereinafter referred to as the compound of the invention) is of great use as a component of the DDS (drug delivery system) device. The term `device` means a material having the function of transporting a physiologically active substance, e.g. a carrier.
BACKGROUND ART
It is known that a device comprising a certain positively charged lipid (for example, a cationic liposome) is useful for the transfer of genes into the cell (e.g. JP-A-4108391, WO91/17424). It is also known that when a nucleic acid such as a double-stranded RNA is administered together with a device such as a cationic liposome, a potentiated interferon inducer action is realized (U.S. Pat. No. 5,049,386). It is generally conjectured that since the nucleic acid of, for example, a gene is negatively charged, it forms a complex with a cationic liposome and the complex becomes fused to the cell membrane and the nucleic acid of the gene or the like finds its way into the cell.
As said cationic liposome, Lipofectin (trademark, Bethesda Research Laboratories Life Technologies Inc.) comprising N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (hereinafter referred to as DOTMA) and dioleoylphosphatidylethanolamine in a ratio of 1:1 is well known.
However, because DOTMA as a component of Lipofectin is a quaternary ammonium compound and, therefore, has high hemolytic toxicity, it is not suitable for pharmaceutical use.
An attempt has been made to enhance the effect of the liposome by replacing the DOTMA of Lipofectin with a cholesterol derivative (Third International Symposium on Catalytic RNAs and Targeted Gene Therapy for the Treatment of HIV Infection, Dec. 6-11, 1992).
DISCLOSURE OF INVENTION
The object of the present invention is to provide a lipid device which is functionally equivalent to the cationic liposome and, yet, is less toxic and a lipid as a component of the device.
In the course of intensive research, the inventors of the present invention discovered that the above-mentioned problems could be solved by using the compound of the invention in lieu of DOTMA in Lipofectin and have completed the present invention.
One of the essential feature of the present invention resides in the structure of the compound of general formula [I]. The compound of the present invention is a novel compound not described in the literature.
The compound of the present invention is structurally characterized in that where glycerol is the fundamental skeleton, one of the hydroxyl groups of glycerol has been substituted by a group formula --A--(CH.sub.2)n-E, where A, n and E are as defined hereinbefore.
Another essential feature of the present invention resides in that A in the above formula --A--(CH.sub.2)n-E is the following 1, 2, 3, 4, 5, 6 or 7. ##STR4##
Among specific compounds of the present invention, none have the amine in the substituent group E in the quaternary ammonium form. It is described in JP-A-4108391 that a lipid having a quaternary ammonium group is satisfactory as a lipid constituent of a liposome or device, but such quaternary ammonium compounds are unsuitable for the purpose of the present invention.
The substituted piperazino for E includes 4-methylpiperazino, 4-
REFERENCES:
patent: 4851232 (1989-07-01), Urquhart et al.
patent: 4853229 (1989-08-01), Theeuwes
patent: 4961932 (1990-10-01), Theeuwes
patent: 5030454 (1991-07-01), Theeuwes
patent: 5252706 (1993-09-01), Kitaguchi et al.
Junichi Yano
Ohgi Tadaaki
Carr Deborah
Nippon Shinyaku Co. Ltd.
LandOfFree
Glycerol derivative, device and pharmaceutical composition does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Glycerol derivative, device and pharmaceutical composition, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Glycerol derivative, device and pharmaceutical composition will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-937608